PMID- 9138321
TI  - [Reoperations for persistent or recurrent gastroesophageal reflux after surgical
      treatment].
AB  - Thirty one cases of failed antireflux surgery were analyzed. The first operation
      had been performed on 24 patients with uncomplicated reflux and 7 patients with
      complicated reflux. There was an abnormality of the cardia in all cases. Twenty
      eight patients had been operated through an abdominal approach and 3 through a
      thoracic approach. The failure was diagnosed during the first year in 12
      patients. The reflux became complicated in 17 cases. Oesophageal stenosis was the
      most common complication. Twenty four patients were reoperated through an
      abdominal approach and 7 through a thoracic approach. In 29 cases out of 31, an
      anatomical cause of the failure was found and rectified. Mortality was nil. The
      results of iterative surgery were good in 80 p. cent of cases after a mean follow
      up of 6 years.

PMID- 9138323
TI  - [Esophageal and cardial risk of treating gastroesophageal reflux by laparoscopic
      surgery].
AB  - A qualitative study of risk was performed on 4 forensic files and on accidents
      published in the literature (1,609 cases). The surgeon may be charged with the
      responsibility of specific complications involving the oeso-cardial-tuberosity
      junction including perforation of the esophagus (13 cases), perforation of the
      stomach (8 cases) and necrosis of the Nissen valve by ischemia after section of
      the short vessels of the lesser curvature (2 cases). Sudden migration into the
      mediastinum or the left pleural space may occur after laparoscopic surgery (23
      cases). As for all surgery, it is the surgeon's responsibility to provide
      adequate means for the indicated procedure and to perform the operation and
      follow-up. Since this is a new technique, the severity of judgements increases
      with the notion of special risk and aggravated risk.

PMID- 9138322
TI  - [Diagnosis of adenopathies and retroperitoneal masses by surgical endoscopy.
      Apropos of 93 cases].
AB  - Lumboscopy is an endoscopic surgical technique providing direct visualization of
      the retroperitoneal space from the kidney hilium to the iliac bifurcation. We
      report our 10-year experience with this technique used to diagnose masses in the
      retroperitoneal space. This method is not very invasive and the morbidity is low.
      The sensitivity is greater than needle biopsy under CT guidance.

PMID- 9138324
TI  - [Lateral brachial flaps].
AB  - The "extreme" lateral arm flap is a new method for covering the distal upper
      limb. This flap is a modification of the classical lateral arm flap allowing his
      transfer as a pedicled flap to cover the forearm and the wrist. This technique is
      based on a new concept: "the reverse flow VY pedicle advancement". This requires
      an arterial bifurcation of the deep humeral artery: the medial collateral artery
      described in this study.

PMID- 9138325
TI  - [Ambulatory treatment and prevention of priapism using alpha-agonists. Apropos of
      172 cases].
AB  - From 1985 to 1995, 172 patients (149 on self intracavernous injection of
      vasoactive drugs, 16 with Sickle cell disease, 6 surgical patients under heparin
      therapy, and 1 after oral administration of trazodone), having experienced one or
      several episodes of priapism, lasting from 3 h to 8 days have been treated or
      submitted to self medication with alpha-agonist agents (eprephrine, phenylephrine
      or etilefrine) with an eventual drainage of the corporae. All episodes have
      disappeared and sexual function was preserved. A conservative treatment of
      priapism has been designed using corporal drainage and intracavernous etilefrine
      for acute priapism; as well as preventive treatment for those of the patients
      exposed to Sickle cell disease to avoid surgery and its frequent fribrotic
      sequelae, leading to impotence in 50% of the cases.

PMID- 9138326
TI  - [An original case of simultaneous cardiac, pancreatic and renal transplantation.
      Results over 6 years].
AB  - Combined transplantation is actually performed on specific and rare indications.
      We are presenting here the results of a combined heart-kidney and pancreatic
      graft. It was performed in a patient presenting an idiopathic cardiomyopathy in
      end-stage failure and a post-diabetic nephropathy on dialysis. Today, organs
      function is quite satisfactory with a 6 year follow-up. Only one isolated heart
      rejection episode was observed at the 15th post-operative day. The patient has
      recovered a full-time professional activity at one year. This successful graft
      was obtained by an "homogeneous multiorgan approach" during all the pre-peri and
      postoperative time.

PMID- 9138327
TI  - [Experimental protocol for mechanical characterization of a femoral implant of
      carbon-Peek composite hip prosthesis in fatigue].
AB  - This study concerns the fatigue behavior of a C/Peek hip implant. It is now well
      established that the extent of bone loss around a total hip arthroplasty stem is
      related to stress shielding process. Due to a modulus mismatch between the bone
      and the implant material, the load transfer to the stem decreases the mechanical
      stimulus needed by the bone to maintain its structure. Because of its low modulus
      of elasticity and its good resistance to fatigue in aeronautical applications,
      the Fiber Carbon/Peek composite could potentially replace some of the metal
      alloys used in hip stem implant. After a literature survey on biomechanical
      performances of some fiber carbon composites, including AS4/Peek, experimental
      quasi-static and fatigue compression tests have been performed on AS4/Peek hip
      implants. The structural and mechanical characterization of the injection moulded
      composite material has been realized. The prosthesis compression and fatigue
      behaviour have been studied with a joint-stimulating apparatus immersed in a
      physiological solution temperature controlled. Instead of the low specimen
      homogeneity, no fatigue damage has been revealed either by X-ray observations of
      stiffness measurements, till ten millions of cycles. The quasi-static compressive
      fracture morphology has been analyzed by S.E.M. and have shown a good fiber
      matrix bonding. This mechanical results would suggest that AS4/Peek hip stem are
      worthy of further investigation as implantable prostheses.

PMID- 9138328
TI  - [Antibiotic release by tricalcic phosphate bone implantation. In vitro and in
      vivo pharmacokinetics of different galenic forms].
AB  - The purpose of this study was to evaluate the load and the release of antibiotics
      obtained with an implant made of a macroporous beta tricalcium phosphate ceramic
      (beta-TCP). Two parameters have been assessed: macroporosity and external shape
      (beads and parallelepipeds). In vitro, the ceramic beads were soaked in a
      Vancomycin-aqueous-solution, and the load of the antibiotic was then evaluated:
      it was 9.3% of the weight of the 40%-porosity beads and 4.6% of the weight of the
      20%-porosity beads. The release has been evaluated by elution in phosphate
      buffered-saline (PBS). With a 20% porosity, 12 beads (6.3 mm, 279 +/- 38 mg)
      demonstrated a short an massive release which ended within the 32 first hours. On
      the opposite, the release was sustained until the third week for the 40%-porosity
      beads (6.9 mm, 353 +/- 25 mg), while only one third of the load was released
      during the first 24 hours. A macroporosity of 40% of the ceramic could allow a
      deep incorporation of the antibiotic in the beads and thus decrease the rate of
      release. The in vivo study compared the bone concentrations of antibiotics
      obtained after implantations of either parallelepipedical or spherical devices in
      the distal femurs of 14 sheep. The bone concentrations of Gentamicin obtained
      with parallelepipeds until the end of the third week were from 5 to 10 times the
      minimum inhibitory concentration of this antibiotic for staphylococci. On the
      opposite, beads achieved only low concentrations of Vancomycin and nearly no
      detectable Gentamicin in the bone. We hypothesize a negative effect of the
      fibrous tissue which fills the gaps between the beads, and which could impair the
      diffusion of the antibiotics into the bone.

PMID- 9138329
TI  - [Diagnostic and therapeutic strategy of insulinomas. Apropos of a personal
      experience of 21 cases].
AB  - Insulinomas account for about 90% of all pancreatic endocrine tumors and their
      surgical resection leads to cure in 90% of patients. Although current laboratory
      tests have simplified the clinical diagnosis of insulinomas, despite recourse to
      an array of most preoperative diagnostic procedures in 10-15% of patients the
      exact location of the tumor remains undefined. Tumor localization is difficult
      because: 80% of insulinomas measure less than 2 cm, about 10-12% of insulinomas
      are multicentric and 4-6% escape detection because are multiple endocrine
      neoplasms (MEN). If preoperative imaging fails to detect the site of the lesion,
      the surgeon could be obliged to perform a "blinded resection" with high risks of
      failure. The Authors refer their experience in a series of 21 patients operated
      on for insulinoma over the past 8 years (1987-1995). Arteriography with calcium
      stimulation (ASVS) and scintigraphy with 111-Indium-labeled octreotide performed
      in the later 16 and 13 cases respectively, achieved a correct tumor localization
      (confirmed by surgery) in 100% and 84.7% of patients. Intraoperative
      ultrasonography, performed in 18 cases, allowed not only to localize the tumor
      but also to study the tumor's neighbouring anatomic structures (Wirsung duct.
      splenic artery and vein), thus providing the anatomical and surgical information
      necessary to plan the right surgical strategy (tumor enucleation or pancreatic
      resection). Tumor enucleation was performed in 15 patients, distal pancreatic
      resections in 5 cases and multiple liver biopsies in 1 case: this patient had
      liver micrometastases from a malignant insulinoma without a palpable tumor.
      Operative mortality was nil. Postoperative complications occurred only in 5 of
      the 15 enucleations (1 pseudocyst successfully treated with a ultrasound-guided
      drainage and 4 pancreatic fistula resolved by medical therapy).

PMID- 9138330
TI  - [Orbital metastasis of prostatic cancer. Clinical and therapeutic aspects.
      Apropos of a case (clinical case)].
AB  - A metastasis to the left orbit revealed cancer of the prostate in a 60-year-old
      man. Such localizations are rare compared with the frequency of bone metastasis
      in cancer of the prostate. Diagnostic methods are discussed together with the
      urgent required to save the eye.

PMID- 9138331
TI  - [Indication of mechanical circulatory assistance].
AB  - Over the last decade, we have seen considerable progress both in medical
      treatment of acute and chronic heart failure and in circulatory assist systems,
      including the first used aorta counter-pulse system. More sophisticated systems
      have been developed with specific indications recognized by specialized teams.
      However, in the treatment of chronic heart failure, whether caused by idiopathic
      dilated cardiomyopathies or ischemic heart disease (frequently improved with
      coronary revascularization), the nature of the disease in patients hospitalized
      in intensive care units has greatly changed. There is a net tendency towards
      hospitalizing older patients who may no longer be reasonable candidates for
      transplantation. The option of circulatory assist is thus undoubtedly reasonable
      for these patients due to the lack of a sufficient number of donor organs.

PMID- 9138332
TI  - [CardioWest, a complete artificial heart, the French experience].
AB  - The development of implantable electric assist systems for the left ventricle
      cannot be used in all patients. Approximately one-third of them who could benefit
      from circulatory support while waiting for transplantation also require a
      supporting system for the right ventricle. In addition, the small number of
      available donor organs means that only those patients with the best prognosis can
      be transplanted. From January 1993 to December 1995, 36 patients (33 men, 3
      women) mean age 41 years (range 19-60) were treated with a total artificial heart
      system, CardioWest at the La Pitie Hospital in Paris and at the Laennec Hospital
      in Nantes, France. Heart assist lasted 1 to 138 days (mean 31 days). Indications
      were terminal heart failure due to dilated (n = 21) or ischemic (n = 11)
      cardiomyopathy and 4 high-risk indications (chronic rejection, primary failure,
      hereditary heart disease, polyvalve disease). Twenty-two of these patients
      (61.1%) were transplanted. By using strict selection criteria, the total
      artificial heart CardioWest was able to maintain satisfactory hemodynamic
      conditions until transplantation without compromising the small number of donor
      organs available. The total artificial heart is the best system available for
      total circulatory support in case of dual ventricular failure. The risk of
      infection is low and the rate of thrombo-embolic events is reduced when care is
      taken in controlling coagulation, allowing long-term support. Independently of
      the experience of the different teams, CardioWest is the only device currently
      available allowing total heart support; its use is justified in particular when
      other assist devices are unsuccessful.

PMID- 9138333
TI  - [Reflections on external circulatory assistance. Apropos of 8 patients treated
      with the MEDOS system].
AB  - Mechanical circulatory support is required when cardiogenic shock is unresponsive
      to well conducted medical therapy. In this hemodynamic situation, when the
      patient's life is in danger, within hours, several questions should be answered
      quickly. These questions take into consideration the etiologies of cardiogenic
      shock and are related to the possibility of improvement of myocardial function,
      cardiac transplantation, the choice of uni- or biventricular support and surgical
      techniques of left ventricular assistance (left atrium to aorta or left
      ventricular apex to aorta). The follow-up of patients with circulatory support is
      complex. It requires to take into consideration hemodynamic, mechanical and
      hemobiological parameters as well as the peripheric organ function. We report in
      this article our clinical experience with eight patients that underwent
      circulatory support with Medos external ventricular assist device.

PMID- 9138334
TI  - [Wearable Baxter-Novacor mechanical ventricular assistance].
AB  - Progressive technological developments have permitted clinical use of the
      wearable Baxter-Novacor left ventricular assist system. The system allows total
      bypass of the left ventricular function, and recovery of and adequate circulation
      in patients in cardiogenic shock. Since the first clinical use, in March 1993,
      eight patients about to die have been supported with a cardiac transplantation.
      This experience suggests that an an acceptable answer to the problem of organ
      shortage is now available.

PMID- 9138335
TI  - [Chemotherapy schedules and bacteremia in adult patients with acute leukemia].
AB  - In a study undertaken to evaluate fluoroquinolone prophylaxis in afebrile
      granulocytopenic patients, an unexpected association between chemotherapy
      schedule and a later development of bacteremia--during the subsequent febrile
      neutropenic episodes--was found. Twenty five febrile neutropenic episodes
      consecutive to chemotherapy for acute leukemia were studied. Patients received
      either etoposide and mitoxantrone or citarabine--in standard, intermediate or
      high doses--combined with daunomicin or mitoxantrone. Microbiologic data analysis
      showed an increased incidence of bacteremia with combined anthracycline and
      intermediate or high dose citarabine administration, when compared to etoposide
      and mitoxantrone use (p = 0.000387). Both groups developed similarly fast and
      severe neutropenias and equivalent grades of digestive mucositis. Chemotherapy
      schedule was the only factor associated with a consecutive bacteremia--or not-
      during the subsequent neutropenic episode. We conclude that effects other than
      bone marrow aplasia and digestive mucositis may be relevant in infectious
      susceptibility induced by cytostatic drugs.

PMID- 9138336
TI  - [Acute promyelocytic leukemia: experience with trans-retinoic acid in Argentina].
AB  - From February 1992 to February 1995, 77 patients with APL were treated with ATRA
      in induction (59 patients de novo, 6 in first relapse, 1 with APL secondary to a
      mielodisplastic syndrome). The dose used was 45 mg/k/day-30 mg/k/day until
      complete remission (CR) was achieved; of the 66 evaluable patients, 50 achieved
      complete remission (78%). Among the 14 patients who did not attain CR, 13 died,
      10 of bleeding episodes and 3 of retinoic syndrome; one was rescued with
      chemotherapy. We proposed consolidation treatment with high dose Ara-C and
      Idarubicin to the 49 patients in complete remission; 6 could not receive it and 5
      died; the disease free survival period of the other patients was 81% (CI95 90%
      66%) at one year and 74% (CI95 91%-52%) at two years. We consider that our
      results are similar to those of other groups and we are inclined to continue with
      this treatment protocol.

PMID- 9138337
TI  - [Concurrence of cytochemical and immune patterns of different cell lines in cases
      of acute leukemia].
AB  - Mixed, bilineal, biclonal and hybrid leukemias are synonymous, differing from
      biphenotypical ones. Mixed acute leukemia is defined by the coincidence of 1) two
      cytochemical markers of different lineage, or 2) one of them with more than one
      opposite immunological marker, or 3) more than one immunological marker opposite
      to another immunological lineage. Seven cases of mixed acute leukemia are
      presented, two of which showed posttreatment switching. It is concluded that
      mixed acute leukemias are associated with a poor prognosis, and therapeutic
      criteria are defined.

PMID- 9138338
TI  - [Incidence, etiology and prognostic value of persistent significant proteinuria
      in kidney transplants].
AB  - We investigated persistent significant proteinuria (PSP), defined as proteinuria
      > 1 gr/24 hours on three consecutive months, in renal allograft recipients. The
      clinical records of 273 patients (288 grafts) were reviewed and 236 grafts (178
      live related, 58 cadaver donor) that functioned for at least 4 months (230
      patients, 148 men and 82 women) were selected for analysis. The histological
      diagnoses of 226 grafts and 35 native kidneys were also reviewed. PSP was present
      in 67 grafts (28.4%); 43 of these grafts were studied histologically (transplant
      glomerulopathy (TxGPT) 19, idiopathic glomerulopathy (GP) 13, and chronic
      rejection 11). Patients with an idiopathic GP in the graft usually presented with
      the nephrotic syndrome (65%); this presentation was infrequent in patients with
      chronic rejection. The appearance of proteinuria was strongly associated with
      functional deterioration in grafts with chronic rejection and TxGPT; in grafts
      with PSP and a histological diagnosis of idiopathic GP, renal function was
      usually normal. Within grafts with PSP no statistically significant differences
      in actuarial survival (AS) could be established when the time of appearance or
      magnitude of PSP, the presence or absence of arterial hypertension, the
      immunosuppressive regimen, and the histological diagnosis were considered.
      Contrariwise, the difference in AS was highly significant (p < 0.0001) when
      grafts with and without PSP were compared. The former had an AS at 5 and 10 years
      of 74.6% and 55.7%, while in the case of the latter AS was 57.3% and 32.1%,
      respectively. In conclusion, in the present series 28.4% of grafts that
      functioned 4 months or more presented PSP. The most frequent glomerular lesion
      was TxGPT. The presence of PSP was a marker for poorer prognosis, since AS at 5
      and 10 years was significantly less in this group.

PMID- 9138339
TI  - [Proximal femoral fractures: risk factors, bone mineral density, body composition
      and biochemical changes in and age-matched patients and controls].
AB  - During one year (6/93-5/94) we performed a prospective study in patients with hip
      fracture, treated at the Hospital de Clinicas. A total of 102 women 52 to 94
      years of age (Mean +/- 1SD: 79.5 +/- 9.1 years) and 17 men 61 to 98 years of age
      (79.7 +/- 9.9 years) who had sustained a hip fracture due to mild or moderate
      trauma were included. The ratio women: men was 6:1. We also studied 55 age
      matched control women without diseases that could affect the skeleton or previous
      hip fracture (77.1 +/- 5.8 years of age). We did not study a control group in
      men. Women with hip fractures had lower weight (p < 0.01), lower age of onset of
      the menopause (p < 0.01) and a tendency to have with a greater frequency a mother
      with hip fracture (p < 0.08) compared with age-matched controls. When vertebral
      fractures were excluded, 44% of the hip fracture women had sustained previous
      skeletal fractures, while only 16% of the age-matched controls had suffered
      previous skeletal fractures (p < 0.001) (Table 2). The most frequent previous
      skeletal fractures were wrist and humerus. Forty eight percent of hip fracture
      women had had at least one vertebral fracture. About 17% of the hip fractured men
      had sustained previous skeletal fractures, while 5/12 men had suffered at least
      one vertebral fracture. Hip fractured women and men sustained greater history of
      diseases which provoke postural instability (Table 3). Biochemical determinations
      showed significantly diminished levels of serum albumin (p < 0.001) and calcium
      (p < 0.01), and increased serum PTH (p < 0.05) compared to age-matched controls
      (Table 4). Bone mineral density (determined by dual energy X-ray absorptiometry)
      was significantly diminished over proximal femur, total skeleton, legs and pelvis
      (p < 0.001), head and spine (p < 0.05) (Table 5). Body composition measurements
      showed that hip fracture women had a significantly lower lean mass compared with
      controls (p < 0.05). Fat mass also was lower in fracture patients compared with
      controls, but the difference was not statistically significant (Table 5). We
      conclude that hip fracture in our population is related to several previous
      factors: earlier onset of menopause, lower nutrition and body weight, previous
      diseases that increase the likelihood of falling, increased levels of PTH and
      reduced bone mass. Prevention of hip fractures should take into account all these
      factors, specially those that could be modified.

PMID- 9138340
TI  - [Pathology of cardiac lesions induced by radiofrequency ablation in an
      experimental model].
AB  - Radiofrequency catheter ablation is increasingly being used for the treatment of
      several tachyarrhythmias. The main aim of this paper is to describe the lesional
      pathology produced by this type of current. Fourteen Wistar rats (mean weight 300
      g) were subjected to discharges of a 700 KHz, pure, unmodulated, sine-wave
      radiofrequency generator. Three rats, through open chests, received epicardial
      shocks and were immediately sacrificed ("acute" lesions). The remaining 11 rats
      received shocks through percutaneously plunged tungsten wires, and were
      sacrificed 1 to 4 weeks after the procedure ("chronic" lesions). Hearts were
      fixed in buffered (pH7) 10% formalin solution. Selected slices were stained with
      hematoxilin-eosin and Mallory trichrome. Other slices were fixed in 3%
      glutaraldehyde and post-fixed in osmium tetroxyde, dehydrated and included in
      Polybed 812. Ultrathin slices were stained with uranil acetate and lead citrate
      and examined in a JEOL JEM-100 C electronic microscope. "Acute" specimens showed
      small coagulation necrosis areas, well delimited by carbonization and
      hemorrhages. Neighbouring myocardium showed one o two rows of moderate cell
      lesions which consisted of cytoplasmic homogeneization and increased contracture
      bands. " Chronic" lesions showed granulation tissue with mononuclear infiltrates
      and neoformation vessels surrounding a central necrosis area. The older the
      lesion, the larger the number of fibroblasts and mature collagen tissue.
      Ultrastructural studies showed irreversible myocardial changes in the lesional
      borders, with cytosolic and myofibrillar edema, contracture bands and rupture of
      mitochondrial crests. Radiofrequency lesions are limited, shallow and with net
      borders, which makes them almost ideal for subendocardial ablation of small
      arrhythmogenic areas.

PMID- 9138341
TI  - [Survey among Argentine physicians on medical decisions concerning the end of
      life in patients: active and passive euthanasia, and relief of symptoms].
AB  - Euthanasia and other medical decisions concerning the end of life (MDEL) have
      been poorly developed in the Argentine medical literature. On that basis, and
      presuming that MDEL occur frequently in the medical practice in our country (in
      spite of insufficient pre and postgraduate medical education on the matter), we
      have developed a survey on MDEL. It was conformed by a 13 multiple-choice
      question poll, which was answered by 172 physicians from Buenos Aires, suburban
      locations and La Plata. The questionnaire began with a professional profile and
      subsequently developed questions on medical, legal, ethical, religious and
      sociologic aspects of MDEL. The questions were based on the main or more frequent
      topics referred to MDEL, according to the medical literature between 1989 and
      1994, researched through Medline. The poll was anonymous. Most of the questions
      could be answered based on the physician's attitudes toward MDEL; some required
      specific knowledge on the subject (as in the questions on legal matters). Three
      different MDEL were defined for this survey: active Euthanasia, Passive
      Euthanasia and Relief of Symptoms. Results showed that MDEL are frequent (69%) of
      the physicians have performed Relief of Symptoms, 58% Passive Euthanasia, and 7%
      Active Euthanasia) and that the physician's knowledge on the subject is poor and
      sparse. We concluded that more research on MDEL is needed in Argentina in order
      to support changes in medical education and legal background.

PMID- 9138342
TI  - Enzyme polymorphism on the metabolic O-demethylation of dextromethorphan in a
      South American population.
AB  - The polymorphic oxidative metabolism of debrisoquine and sparteine were
      discovered in the seventies by Mahgoub and Eichelbaum. Since then, many other
      therapeutic substances were added and one of these drugs is dextromethorphan. The
      object of this investigation was to ascertain the distribution of the oxidative
      phenotype of dextromethorphan in the Uruguayan population. The drug and its
      metabolite, dextrorphan, were quantified in the urine of 165 healthy volunteers
      by modification of an HPLC method by Chen et al. The metabolic ration was
      calculated and frequency distribution histograms were drawn. By inspection of the
      histogram two antimodes can be assigned which determine three sub-populations: on
      one side the fast extensive metabolizers (n = 30, 18.2%), in the middle the
      extensive metabolizers (n = 123, 74.5%) and on the other extreme of the histogram
      the slow metabolizers (n = 12, 7.3%). No other studies have confirmed thus far
      this trimodal distribution. This research will be continued by genotyping the
      populations studied in order to confirm these findings and to elucidate the
      underlying genetic mechanisms of the polymorphism.

PMID- 9138343
TI  - [Seroepidemiology of Chagas disease in the Province of Jujuy].
AB  - Chagas disease is the principal zoonosis of the Province of Jujuy where it
      represents a major public health problem. In this paper the results of a
      serological screening of T. cruzi infection carried out in the Province of Jujuy
      are analyzed to determine the general prevalence, age and geographic
      distribution, sex ratio, prevalence in foreign population and their relation with
      migratory process. In every individual (N = 16482) indirect hemagglutination
      (IHA) and immunofluorescence (TIF) tests have been carried out. In 5879 of them
      the birth place in the territory of the Province and the number of foreign
      individuals (313, all Bolivians) were confirmed. Based on these data the
      individuals were grouped according to: a) the four geographical regions of the
      Province located at different altitude levels, Puna, Quebrada, Valle and Ramal;
      b) towns placed on or away from the main routes of communication of the Province.
      For the statistical analysis the X2 and Z tests were employed. The results show
      that: 1) the general prevalence was of 11.50%; 2) no differences existed between
      the sexes: 3) the region with the highest prevalence was the Valley (12.84%)
      followed by Ramal (10.43%), Quebrada (8.53%) and Puna (2.98%); 4) differences of
      the serum prevalence can be observed between the residents on and away from the
      main routes of communication denoting the existence of a migratory effect in the
      distribution of chagasic infection; 5) prevalence differences exist between
      naturalized foreigns (39.30%) and Argentines (10.25%), data which strengthen the
      previous remark. Except for the general prevalence, there are no similar
      serological surveys which might allow us to establish relationships with our
      results of which the outstanding one is the influence of the migratory aspect
      upon the prevalence and distribution of T. cruzi in the Province of Jujuy.

PMID- 9138344
TI  - Age-dependent morphological changes in dBcAMP-treated astrocytes.
AB  - Since changes in cell morphology are conspicuous features of astrocyte reaction,
      we resorted to an histometric approach to evaluate age influence on such
      morphological response to activating stimuli. To this end, first subculture of
      rat brain astrocytes at 1, 9 or 21 days in vitro (DIV) were treated during 2 hs
      with 1 mM of dBcAMP, a chemical compound known to induce cell differentiation.
      Following treatment, immunoperoxidase labeling of GFAP, specific marker of
      astrocyte activation, was carried out. Although total count of GFAP-positive cell
      foci was greater in treated samples in all times tested, when such cell foci were
      evaluated by image analysis, differences between perimeter/area ratios of such
      foci were only statistically significant at 1 DIV. It may be concluded that while
      dBcAMP effect is maintained despite astrocyte aging, the morphological pattern of
      response varies markedly along the observation period.

PMID- 9138345
TI  - The role of apoptosis in the inhibition of a secondary tumor by concomitant
      resistance in a mouse model of metastases.
AB  - Resistance of tumor-bearing mice to a second tumor challenge, that is,
      concomitant resistance, was studied using the LB tumor model. In a secondary LB
      tumor implant inhibited by concomitant resistance an increase in the percentage
      or apoptotic cells and alterations in cell cycle distribution were observed.
      Similar alterations were observed in LB tumor cells incubated with serum from
      tumor-bearing mice. The data presented in this paper suggest that apoptosis is
      one of the mechanisms involved in tumor dormancy due to concomitant resistance.

PMID- 9138346
TI  - [Primary lung Kaposi sarcoma associated to AIDS in a heterosexual drug addict
      man].
AB  - A case of lung Kaposi sarcoma (KS) in the absence of cutaneomucosal lesions was
      observed in a 30-year-old heterosexual male with AIDS and a history of
      intravenous drug addiction. Both chest X-ray and CT scanning disclosed a diffuse
      nodular pattern in lungs, whereas endoscopy failed to demonstrate endobronchial
      damage. Cytological examination of the sample taken by transthoracic lung
      puncture proved compatible with primary KS, a rare neoplasia in heterosexual male
      drug addicts with AIDS. A year following the diagnosis of KS, the patient died of
      respiratory failure.

PMID- 9138347
TI  - [Respiratory infection in a man with systemic lupus erythematosus].

PMID- 9138348
TI  - [Medical treatment of colorectal cancer].
AB  - Colorectal cancer is the second leading cause of cancer-related death in the US
      in both sexes after lung cancer. In 1995 colorectal cancer became the third most
      common neoplasm after lung and prostate cancer in men and after lung and breast
      carcinomas in women. The etiologic factors related to this disease are unknown
      although environmental, genetic, dietary and familial factors have been
      implicated. From the standpoint of the treatment it is important to remark that a
      high percentage of patients with colorectal cancer are curable if the disease is
      diagnosed in early stages. Adjuvant therapy with 5-fluorouracil (5-FU) and
      levamisole (lev) has shown an increase in the cure rate in stage III (Dukes'C)
      colon cancer patients. In rectal cancer patients adjuvant therapy with
      chemotherapy and radiation therapy increased the cure rate in stages II (Dukes'
      B2) and III patients. When colorectal cancer is disseminated (stage IV or
      Dukes'D), it is incurable in the majority of the patients. In fact, the only
      curative possibility in this group of patients is, when indicated, surgical
      resection of the metastatic focus. If resection is unfeasible, palliative
      treatment with 5-FU-based chemotherapy is the usual approach. Regardless of the
      advances made in treatment, almost 50% of the colorectal cancer patients still
      die due to progression of their disease. Better programs of primary and secondary
      prevention, new therapeutic modalities and better chemotherapeutic agents will be
      necessary to improve survival in colorectal cancer patients.

PMID- 9138349
TI  - [Colorectal cancer: surgery or is there something else?].
AB  - The standard modality to treat colorectal cancer in potentially curable patients
      is, undoubtedly, surgery. The concept of precautional chemotherapy used in tumors
      located elsewhere, has put forward a clinical trial that proved its effectiveness
      and improved survival. We report the use of two modalities (chemotherapy and
      radiotherapy) along with surgery as part of a multidisciplinary treatment of
      patients with colorectal cancer.

PMID- 9138350
TI  - [Guidelines for withdrawing or refusal to provide vital support in patients in
      irreversible clinical situations Ethics Committee, Community Private Hospital,
      Mar del Plata].

PMID- 9138351
TI  - [Looking at homeopathy, by an allopath].

PMID- 9138352
TI  - [Nuclear curriculum: new model in the medical education].

PMID- 9138353
TI  - [In vitro susceptibility testing of 446 clinical isolates of gram-positive
      bacteria to new quinolones, carbapenems and cephalosporins].
AB  - OBJECTIVE: To assess the in vitro susceptibility of gram-positive bacteria
      isolated in the Sao Paulo Hospital against five fluoroquinolones, three
      carbapenems and three cephalosporins. MATERIALS AND METHOD: Susceptibility was
      tested in 77 isolates of streptococci, 38 enterococci, 25 S. aureus and 91 S.
      epidermidis. The strains were isolated in the Sao Paulo Hospital in June and July
      of 1992. The susceptibility testing was performed by broth microdilution
      according to the procedure described by the national committee for Clinical
      Laboratory Standards (NCCLS). The antimicrobial agents tested were:
      ciprofloxacin, ofloxacin, levofloxacin, grepafloxacin (formerly OPC 17116), DU
      6859, imipenem, meropenem, biapenem, ceftazidime, cefepime and FK-037. RESULTS:
      The best in vitro activity was demonstrated by the new fluoroquinolones,
      especially DU 6859. Among the commercially available compounds, the
      fluoroquinolones ciprofloxacin and ofloxacin (81% susceptibility) and the
      carbapenem imipenem (74% susceptible) were the most active compounds. The highest
      resistance rates were shown by enterococci and oxacillin-resistant staphylococci.
      CONCLUSIONS: The results of the present study showed that the in vitro activities
      of the new carbapenems are similar to that of imipenem and the fourth generation
      cephalosporins are more active than ceftazidime against gram-positive bacteria.
      In addition, the newer fluoroquinolones were four to sixteen-fold more active
      than that showed by the commercially available compounds of this class,
      especially against enterococci and oxacillin-resistant staphylococci. These
      results indicate that these newer fluoroquinolones should be further evaluated in
      clinical trials.

PMID- 9138354
TI  - [Study of pulmonary epithelial permeability in healthy non-smokers].
AB  - OBJECTIVE: To measure the pulmonary epithelial permeability in non-smoker healthy
      adult individuals, establishing the normal pattern in our milieu and to correlate
      the findings according to age, sex, weight, height and body surface area. METHOD:
      24 healthy non-smokers using the rate of pulmonary depuration of 99mTc-DTPA as an
      index of pulmonary epithelial permeability were studied. The given information
      was correlated to sex, age, weight, height and body surface area. RESULTS: The
      averages found for the pulmonary depuration rate for 99mTc-DTPA were 0.82% +/-
      0.19 min-1 for the left lung and of 0.88% +/- 0.23 min-1 for the right lung. No
      statistically significant relation with sex, age, weight, height and body surface
      area was found. CONCLUSION: The given data are within the interindividual
      variation described in the literature, in the studied age period, and must be
      considered as standard values among us.

PMID- 9138355
TI  - [Value of determining the activity of adenosine deaminase (ADA) in the
      differential diagnosis of pleural effusions].
AB  - BACKGROUND: Pleural effusion (PE) is a common problem in medical practice.
      Transudative effusions usually do not present difficulty in diagnosis, in most
      populations. Exudative PE however, require careful differential diagnosis that
      include necessarily tuberculosis and metastatic cancer. METHODS: We have
      conducted a cross-sectional study of 221 patients with persistent PE, in order to
      evaluate accuracy of determining adenosine deaminase activity (ADA) for diagnosis
      of tuberculosis pleuritis. This group of patients, taken mostly from the State
      Hospital for pulmonary diseases, consecutively, was constituted as follows: 1)
      Tuberculosis (confirmed, n = 150; likely, n = 9); 2) Cancer (confirmed, n = 21;
      likely, n = 16; Lymphoma = 3); and 3) Miscellaneous (n = 22). All individuals
      were submitted to clinical examination, chest X-ray, blood tests, and underwent
      thoracocentesis with pleural biopsy. Pleural fluids were analyzed by routine
      tests plus determination of ADA activity using Giusti's Method. RESULTS: In
      agreement with previous reports we have found 40 U/L to be the best cutoff point
      according to a Receiver Operating Curve (ROC) analysis of our data. Sensitivity
      of ADA activity < or = 40 U/L was 93.3% and specificity 93.5%, resulting in a
      positive predictive value of 97.2% and a negative predictive value of 85.3%, in
      this specific population of patients, when taking into account only the
      individuals with confirmed tuberculosis by histopathology or culture. Three out
      of the 4 patients with elevated ADA without tuberculosis had lymphoma.
      CONCLUSION: ADA determination in pleural fluids, a quick and inexpensive
      technique, is shown to be an accurate method for identifying tuberculosis
      pleuritis. Our findings are comparable to reports from other series, and stress
      how useful it is to incorporate this test to the routine evaluation of pleural
      effusions in areas of high incidence of tuberculosis.

PMID- 9138356
TI  - [Study of the susceptibility of Staphylococcus sp. and Enterococcus sp. to
      teicoplanin and vancomycin].
AB  - PURPOSE: The study was performed in order to evaluate the susceptibility of
      Enterococcus and Staphylococcus to teicoplanin and vancomycin. METHODS: 150
      Enterococcus strains and 450 Staphylococcus strains (298 Staphylococcus aureus
      and 152 negative coagulase strains) isolated in three Brazilian hospitals were
      studied. The MICs were determined using teicoplanin and vancomycin E Test strips.
      The range of the antimicrobial concentration in each strip went from 256 mcg/mL
      to 0.016 mcg/mL. Diffusion tests using disks impregnated with 10 mcg of
      teicoplanin and 30 mcg of vancomycin were also performed. RESULTS: All the 298
      Staphylococcus aureus strains were susceptible to the two antimicrobials. Three
      of the 152 negative coagulase strains presented intermediate susceptibility to
      teicoplanin (MICs between 8 and 16 mcg/mL). Four of the 150 Enterococcus strains
      presented intermediate susceptibility to vancomycin but were totally susceptible
      to teicoplanin. CONCLUSION: According to these results teicoplanin and vancomycin
      are good therapeutical options in the treatment of staphylococcal and
      enterococcal infections.

PMID- 9138357
TI  - [Reconstructive surgery of the upper lip with esthetic-functional recovery].
AB  - Two cases are reported of reconstructive surgery of the upper lip in patients who
      had squamous cell carcinoma, using the Burrow technique. This technique is more
      used in lower lips because it does not involve esthetic unity. We have opted for
      it in the upper lip also, using a variation in the lip commissure incision,
      getting a significant functional and esthetic result.

PMID- 9138358
TI  - [Weight of the newborn in relation to maternal weight gains in 513 normal
      pregnancies: analysis of different stages of the maternal weight at the onset of
      pregnancy].
AB  - The average weight of the newborns (3,293 g; SD = 460) was studied in 513 normal
      pregnancies (free of clinical and obstetrical intercorrencies) and it was
      correlated to: a) maternal average weight gain (12,355 g; SD - 4,067) and b)
      maternal average weight at the onset of pregnancy, both with positive linear
      relation. It was noted too that the relation between maternal weight gain and
      weight of newborns gradually decreased as the comparison involved higher initial
      weight of the mothers. Actually, in the group of average initial weight above 79
      kg no relation was found between maternal weight gain and the weight of the
      newborn. Results were compared to those in the literature and it was concluded
      that the influence of maternal weight gain upon that of the newborn varies with
      the maternal initial weight: 1) in the group of lower and normal initial average
      maternal weight there is an important influence on the average weight of the
      newborn; 2) in the group of initially overweight mothers (above 70 kg) the
      average weight of the newborn was high, but independent of maternal weight gain.
      Thus, caloric restriction in the latter group should be revised.

PMID- 9138359
TI  - [Trends in the graduation of Brazilian physicians].
AB  - Physicians numerical increment in Brazil presented critical variations in recent
      years. So, annual means of graduated physicians were: 1972-1976, 7,082; 1977
      1981, 8,304; 1982-1986, 7,542; 1987-1991, 7,058. In spite of this tendency to
      reduction, physicians per 10,000 inhabitants rate increased in the last 20 years:
      5.96 in 1972, 4.59 in 1982 and 13.87 in 1992. Percentual increment of physicians
      per year represents 3.5% of the total number of active professionals/against less
      than 2% in the total population increase in Brazil. Thus that rate has a clear
      tendency to increase in the next years.

PMID- 9138360
TI  - [Ethical guidelines for scientific research in human individuals supported by
      FAPESP. Bioethics Group and Population Research].
AB  - Ethical guidelines were developed for research projects involving human groups in
      biomedical and human sciences areas. The text is divided into four parts:
      premises, principles, procedures and recommendations. The granting agency will
      institute an Ethical Review Board to mediate ethical conflicts identified in the
      research project. It is intended for the guidelines to be reviewed in 3 to 4
      years.

PMID- 9138361
TI  - [Diagnostic limitations of the physical examination in the identification of
      children with anemia].
AB  - A total of 143 children was randomly selected from a Pediatric out-patients
      clinic in order to evaluate the accuracy and reproductibility of the clinical
      signs of anemia. The patients, who ranged from 6 to 68 months old, were assessed
      on the basis of 2 clinical examinations performed independently by 2 physicians.
      Clinical diagnosis of anemia relied upon the examination for the presence of
      pallor through an inspection of the skin, conjunctivaes, lips, tongue and palms.
      The reference standard taken into consideration was hemoglobin in venous blood
      samples. The prevalence of anemia (hemoglobin < 11.0 g/dL) consisted of 41.3%,
      predominating among patients who ranged from 6 to 24 months old (59.3%). The
      sensitivity of the different clinical signs for the 2 examinations was low ranged
      from 28.8% to 52.5%. Almost all the children with hemoglobin concentration lower
      than 9.0 g/dL presented at least one suggestive clinical sign of anemia. The
      Kappa coefficient (K) demonstrated a mild agreement between the 2 examinations
      for the assessment of cutaneous pallor (K = +0.32) and moderate agreement for the
      evaluation of the conjunctivaes, lips-tongue and palms (K from +0.55 to +0.59).
      In view of limitation of the accuracy and reproductibility of the clinical signs
      of anemia, we may state that the determination of hemoglobin concentration should
      be introduced as a routine procedure of major importance in health care services.

PMID- 9138362
TI  - [Interconsultation psychiatry in general hospitals: initial communication of an
      experience].
AB  - BACKGROUND: Consultation-Liaison Psychiatry is very incipient in Brazil.
      Brazilian psychiatrists are carefully producing new services and research in this
      field. PURPOSE: The authors investigated a Consultation-Liaison's Service
      establishment and first six months in a teaching Hospital in Sao Paulo, Hospital
      Universtario, from Universidade de Sao Paulo. METHODS: Between March and
      September in 1993, there were 60 consecutive referrals from physicians, diagnosed
      using DSM-III-R's (1987) Multiaxial Diagnosis. RESULTS: They found that 85% of
      the sample had an Axis I diagnosis, and the most prevalent were Organic Mental
      Syndromes, Depressive and Anxiety Disorders. This results are similar to the
      consultation-liaison's literature. They found Mental Retardation, Borderline and
      Dependent personality disorders the most important Axis II diagnosis, suicide
      attempts the most stressful life event, and almost half of the referrals scored
      less than 60 in Global Assessment and Functioning Scale applied to the
      internation's period, suggesting that the institutional distress is a very
      important sort of referral's threshold. CONCLUSIONS: The authors conclude that
      Multiaxial Diagnosis is very important to potentialize Consultation-Liaison
      effectiveness in General Hospital, with a contribution to Medicine and every
      staff's member.

PMID- 9138363
TI  - [Safety rules for patients with artificial cardiac pacemaker].
AB  - The recent progress in cardiac pacing increased the usefulness of artificial
      pacemakers. The initial purpose of avoiding Stokes-Adams attacks, was changed by
      a complex way to completely give back the physiologic response of cardiac rate
      and atrioventricular synchronism. However, this process forced the patients to
      take care of their pacemakers, and to spend more time in follow-up procedures.
      Additionally, the pacemakers became more vulnerable to environmental and hospital
      interferences. Basic rules, for all patients, are described in this paper, in
      order to improve their quality of life. Follow-up procedures are related in
      detail. It is described how programmed electronic evaluations can contribute to
      avoid complications, to detect subclinic problems and to improve the patient's
      haemodynamics and physical capacity. It shows also how to use complementary
      examinations, like thoracic X-rays, exercise testing and Holter monitoring to
      optimize the cardiac pacing system. Interferences in pacemakers are focused with
      special attention to myo-potentials, environmental electromagnetic fields, and
      damage to system owing to medical procedures, like therapeutic radiation,
      defibrillation and electrocauterization. The approach to infective processes in
      pacemakers gives special emphasis to prevention of direct surgical contamination,
      erosion of the skin, and haematogenic dissemination of distant infective focus.

PMID- 9138364
TI  - [Hemophilia A: analysis of intron 18 and intron 7 of factor VIII gene and their
      role in a diagnostic strategy for carrier detection in a Chilean population].
AB  - Hemophilia A is an X-linked disorder of coagulation caused by a deficiency of
      factor VIII. A larger number of different mutations in the VIII gene have been
      identified. Thus, the detection of female carriers, depends upon the analysis of
      DNA polymorphisms in and near the factor VIII gene. Our aim was to develop a
      strategy, earlier reported, for carrier testing in families at risk of hemophilia
      A. In this study, we analyzed the DNA polymorphisms in 26 affected families, with
      use of the factor VIII intragenic polymorphisms identified by the restriction
      enzymes BclI and AlwNI, and by differential hybridization with sequence-specific
      oligonucleotide probes recognizing BclI and AlwNI polymorphism. While the DNA
      polymorphism detected by BcilI site in intron 18 of the factor VIII gene was
      informative for 38% families studied, the AlwNI/intron 7 polymorphism provided
      additional information (4%). The carrier status of the remaining 58% could be
      determined utilizing the other polymorphisms suggested by strategy. The two
      polymorphic sites used combined with the other polymorphisms, intragenic and
      extragenic, can generate levels of informativeness greater than 98%. We concluded
      that the strategy for carrier testing would be a good alternative in genetic
      counselling for hemophilia A, but its limitations must be carefully taken into
      account.

PMID- 9138365
TI  - [Acute myocardial infarction in Chile: differences between men and women in its
      evolution and prognosis. Multicenter Study Group on Infarction] (GEMI)].
AB  - BACKGROUND: Gender may be a prognostic factor for the evolution of acute
      myocardial infarction and women may have higher mortality and complication rates.
      AIM: To study if there are differences in the evolution of acute myocardial
      infarction between men and women. PATIENT AND METHODS: We have recorded
      information on risk factors, clinical evolution, treatment and complications of
      2,052 patients hospitalized for acute myocardial infarction in 36 Chilean
      hospitals. The odds ratio for female sex and mortality was calculated using a
      logistic regression analysis adjusted for risk factors, treatment, invasive
      procedures and complications. RESULTS: Twenty six percent of analyzed patients
      were female. Mortality rates among females and males were 11.8 and 20.2%
      respectively (p < 0.01). Women had higher frequency of smoking, diabetes, obesity
      and hypertension. Blood lipid levels were similar in both sexes. Compared to men,
      a lesser proportion of women were treated with thrombolytic agents (25 and 35%
      respectively), intravenous heparin (54 and 61% respectively), beta blockers (31
      and 42% respectively) and intravenous nitrates (53 and 61% respectively). Also,
      women were subjected to less invasive procedures. The odds ratio for mortality
      and sex was 1.72 (confidence interval from 1.13 to 2.62). CONCLUSIONS: Female sex
      is an independent risk factor for acute myocardial infarction mortality.

PMID- 9138366
TI  - [Gallstone dissolution in an adult female population: trial with lovastatin
      therapy].
AB  - BACKGROUND: There are no chilean reports on gallstone dissolution using oral
      medications. AIM: To measure the proportion of asymptomatic adult women eligible
      for gallstone dissolution therapy and to test the effectiveness and tolerance of
      lovastatin for this purpose. SUBJECTS AND METHODS: Three hundred fifty six women
      working at health care institutions were subjected to a gallbladder ultrasound
      examination. Non pregnant women with radiolucent gallstones of less than 2 cm phi
      were invited to receive lovastatin 20 mg od and were followed during six months.
      RESULTS: Twenty two women had gallstones and eight eligible women received
      lovastatin therapy. No reduction in stone size was observed in these women.
      CONCLUSIONS: Less than half of asymptomatic women with gallstones are eligible
      for oral dissolution therapy. Lovastatin did not reduce gallstone size after six
      months of therapy.

PMID- 9138367
TI  - [Lipoprotein in children and adolescents: relationship with family history of
      coronary artery disease].
AB  - BACKGROUND: Lipoprotein (a) is considered an independent cardiovascular risk
      factor. AIM: To study lipoprotein (a) levels in children of 18 years old or less
      with or without family history of coronary artery disease. SUBJECTS AND METHODS:
      Forty four children aged between 3 and 18 years old with a family history of
      coronary artery disease and 44 age and sex matched controls were studied. A
      fasting blood sample was obtained to measure total, HDL and LDL cholesterol,
      triglycerides, A1 and B apoproteins and lipoprotein (a). RESULTS: Compared to
      controls, children with a family history of coronary disease had higher total
      cholesterol (177 +/- 35 and 159 +/- 23 mg/dl respectively), LDL cholesterol (112
      +/- 34 and 94 +/- 21 mg/dl respectively), triglycerides (89 +/- 38 and 71 +/- 25
      mg/dl respectively), apoprotein B (85 +/- 17 and 65 +/- 13 mg/dl respectively)
      and lipoprotein (a) (40 +/- 50 and 22 +/- 31 mg/dl respectively). Thirty two
      percent of children with positive family history had lipoprotein (a) levels over
      30 mg/dl, compared to 23% of controls. CONCLUSIONS: Children with family history
      of coronary artery disease have higher levels of cholesterol, triglycerides and
      lipoprotein (a) than matched controls.

PMID- 9138368
TI  - [Nationally produced 153SmEDTMP in the palliative treatment of metastatic bone
      cancer pain].
AB  - 153SmEDTMP was obtained from enriched 152Sm irradiated at the 5 MW Chilean
      Research Reactor and labelled at a molar ratio of 15:1 pH 7.5. Biodistribution,
      autoradiography, radiochemical purity tests were done for evaluation. 40 patients
      were treated with 37-55 MBq/kg weight. Bone scans using 99mTcHMDP were obtained
      prior and after treatment. Bone marrow depression was observed in 37% of them and
      normal liver function in all of them. In 45% the pain dissapear completely, in
      22.5% significantly decreased and partially in 30%. In 17 patients more than one
      dosis was injected. Our preliminary results indicate that 153SmEDTMP is a
      promising radiotherapeutic agent for palliative treatment of metastatic bone
      cancer pain and encourage its use specially because it can be produced in
      countries with low economic resources, thus a large number of patients can get
      the benefits of this new procedure.

PMID- 9138369
TI  - [Patients with acute adult respiratory distress syndrome: effects of inhaled
      nitric oxide on gas exchange and hemodynamics].
AB  - BACKGROUND: Adult respiratory distress syndrome is highly prevalent in intensive
      care units and has a high mortality. Lately, nitric oxide has been used as
      adjuvant therapy. AIM: To study the effects of nitric oxide inhalation in
      patients with adult respiratory distress syndrome. PATIENTS AND METHODS: Twelve
      patients with adult respiratory distress syndrome, were subjected to nitric oxide
      inhalation at a concentration of 10 parts per million, during 30 minutes.
      RESULTS: At the end of the nitric oxide inhalation period, there was an
      improvement of PaO2/FIO2 ratio from 89 +/- 32 to 111 +/- 43 mm Hg and a 16%
      reduction of lung shunting (Qs/Qt). CONCLUSIONS: Nitric oxide inhalation at a
      concentration of 10 parts per million improved arterial oxygenation and reduced
      pulmonary shunting in patients with adult respiratory distress syndrome.

PMID- 9138370
TI  - [Felodipine in the treatment of essential arterial hypertension in elderly
      patients].
AB  - BACKGROUND: Felodipine is a calcium channel inhibitor with high vascular
      selectivity. AIM: To study the effectiveness of felodipine in the treatment of
      essential hypertension in subjects older than 64 years old. PATIENTS AND OUTCOME:
      Fifty subjects were studied. After a washout period of four weeks, subjects
      received a placebo for two weeks followed by the active drug given in an initial
      dose of 5 mg/day, adjusted to 10 and 20 mg every 21 days if normal blood pressure
      levels were not attained. RESULTS: Compared to the placebo period, Felodipine
      treatment reduced blood pressure from 173 +/- 7.5/102 +/- 3.3 mm Hg to 158 +/-
      6.3/91 +/- 4.2 mm Hg. There was no orthostatic reduction of blood pressure, and
      87% of subjects attained systolic and diastolic pressure levels below 140 and 90
      mm Hg respectively. Adverse reactions (edema, cephalea and flushing) were
      reported by 38% of subjects and in three, the drug was discontinued. There were
      no changes in laboratory parameters during the treatment period. Quality of life
      improved during treatment in the items of concentration, health status
      perception, mood, physical condition, depression, effects of hypertension on life
      events and initiative. CONCLUSIONS: Felodipine is effective in the treatment of
      elders with essential hypertension.

PMID- 9138371
TI  - [Osteoporosis in men under 65 years old presenting as vertebral crushing:
      idiopathic or secondary? Study of 9 cases].
AB  - BACKGROUND: Osteoporosis in young or middle age men is unusual and requires an
      extensive diagnostic work-up. AIM: To report a retrospective review of nine men
      with osteoporosis. PATIENTS AND METHODS: The charts of nine men aged 27 to 61
      years old (mean 39), that presented with a primary diagnosis of osteoporosis,
      were reviewed. RESULTS: Subjects were subjected to a diagnostic work up five
      years after the onset of symptoms. Their body mass index ranged from 21.7 to 26.3
      kg/m2, all had vertebral fractures (crush fractures in 8 and a biconcave
      deformity in one) between T4 and L4 and all had normal serum calcium, phosphate,
      alkaline phosphatase and creatinine. Four patients had a history of
      nephrolithiasis and three had hypercalciuria. Bone density, measured in seven
      patients with a dual photon densitometer, showed a mean Z score of -2.0 in the
      spine and of -2.2 in the femoral neck. The final diagnoses of these patients were
      Cushing's disease in two, malabsorption syndrome in one, use of phenobarbital and
      hydantoin in one, overt renal hypercalciuria with low calcium intake in one and
      alcoholic liver disease in one. In three patients, osteoporosis was considered
      idiopathic. Of these, two had moderate absorptive hypercalciuria as a presumable
      risk factor. CONCLUSIONS: Six of the nine studied male patients with osteoporosis
      had an underlying cause and in three, this condition was considered idiopathic.

PMID- 9138372
TI  - [Dichotomization of continuous variables in logistic regression models].
AB  - It is highly to observe in the biomedical literature, that the continuous
      variables such as systolic blood pressure and cholesterol, are dichotomized and
      used in such manner in a given statistical analysis. The consequences of such
      transformation can be very varied. In this article, how the dichotomization of a
      continuous exposure variable affects the quality of the prediction of a response
      using the logistic regression is examined. One can conclude that, in almost all
      the studied stimulation, the percentages of misclassification can increase
      drastically, reaching over there times the probability of misclassification of
      the ones using the original variable. Therefore, we recommend to avoid
      dichotomization.

PMID- 9138373
TI  - [A case of benign cutaneous polyarteritis nodosa].
AB  - Cutaneous polyarteritis nodosa is a benign form of the disease with cutaneous
      involvement and occasional systemic manifestations. We report a 51 years old man
      presenting with malaise, arthralgia, myalgia and nodular, erythematous and
      painful skin lesions in both legs. The pathological study of these lesions showed
      a polyarteritis. During hospital stay there was a mild remission of the disease
      without treatment, but its reappearance during follow lead to the use of
      prednisone.

PMID- 9138374
TI  - [Pulmonary thromboendarterectomy: a case of surgical treatment of chronic
      pulmonary thromboembolism under circulatory arrest with deep hypothermia].
AB  - Pulmonary thromboendarterectomy under circulatory arrest and deep hypothermia is
      presently a curative treatment for pulmonary hypertension secondary to chronic
      pulmonary artery thromboembolic occlusion, but is still not frequently performed
      around the world. We report here the first successful pulmonary
      thromboendarterectomy under circulatory arrest performed in Chile. The patient
      was a 37 year old white man, high school teacher, with a 5 months history of
      effort dyspnea and cough. Pulmonary hypertension secondary to chronic pulmonary
      thromboembolism was confirmed by angiography and echocardiography. The patient
      was operated on April 27, 1995. After the operation the patient had an immediate
      and maintained normalization of his pulmonary hemodynamics. He presented periods
      of delirium that postponed mechanical ventilation disconnection until the 7th
      postoperative day, after which he had an uneventful neurological recovery. Before
      hospital discharge a control angiography showed complete patency of the pulmonary
      artery system with no evidence of residual thrombi. Presently he is enjoying a
      normal life and back to his teaching activities.

PMID- 9138375
TI  - [Pancreas divisium as a cause of chronic pancreatitis. Clinical case].
AB  - We report a 6 years old girl with chronic pancreatitis, presenting as recurring
      bouts of abdominal pain and hyperamylasemia, secondary to a lack of communication
      between the main papilla and pancreatic duct (pancreas divisium). The diagnosis
      was made during an intraoperative pancreatography and treatment consisted in a
      sphincteroplasty of the secondary papilla.

PMID- 9138376
TI  - [Is timing important in adjuvant radiotherapy?].
AB  - The timing of adjuvant radiotherapy is subject of debate at clinical and
      administrative levels and of concern for the treating physician and also the
      patient. There is a lack of prospective randomized studies dealing with this
      point and it is highly unlikely that they could be carried on. However there is
      evidence coming from the laboratory and retrospective clinical studies which
      could be of help. Data from the laboratory tell us that the Tpot (potential
      doubling time) of a solid tumor is brief, which means that a tumor can grow
      easily while the patient waits for treatment. This means that will be an increase
      in the risk of local and distant relapse. Clinical evidence coming from studies
      of head and neck cancer, breast cancer and small cell lung cancer suggest that
      delay should be limited only to a few weeks. IN CONCLUSION: radiotherapy should
      be started as soon as possible.

PMID- 9138377
TI  - [Molecular and genetic features of fragile X syndrome].
AB  - The fragile-X syndrome is the most frequent cause of sexlinked mental
      retardation. In the majority of the cases the mutation responsible for the Martin
      Bell syndrome is produced when an expansion of the (CGG)n repetition is present
      in the region 5' of the exon 1 of the gene for X-fragile mental retardation 1
      (FMR1), together with a hipermethylation in the CpG promoter region of the gene.
      The result of this situation is the absence of FMRP protein coded by the gene.
      The correlation between length of the (CGG)n sequences and of the X-fragile
      phenotype has permitted a more precise diagnosis of affected and carrier
      individuals by means of direct DNA analysis. Nevertheless the molecular genetic
      basis of the instability and expansion of the (CGG)n sequence represents a
      problem not yet resolved. Two polymorphic microsatellite (AC)n repetitions,
      FRAXAC1 and FRAXAC2 that flank the FMR-1 gene have been recently described. It
      has been suggested that some haplotypes of FRAXAC1 and FRAXAC2 could be
      associated to long (CGG)n repetitions and that these haplotypes would confer more
      instability to the repeated fragment thus increasing the probability of
      expansion. It has also been described that the (CGG)n repetition of the FMR-1
      gene is interrupted by AGG trinucleotides and that the loss of one AGG would be
      an important mutational event in the generation of predisposing unstable alleles
      of of the X-fragile syndrome.

PMID- 9138378
TI  - [Physicians' strikes and health services: an ethical perspective].
AB  - For the public opinion, medical strikes are a controversial issue; physician's
      ethical judgments are also different. The present article analyses the requisites
      to consider legitimate a strike and, based on these, the ethical duties of
      physicians; the features of medical unionism; the ethical duties of authority;
      the manipulation of ill people by the strike and the social factors that may
      cause these conflicts. In a medical strike, universal ethical values based on the
      Hyppocratic oath and promoted by the profession, are endangered. This article
      concludes that a medical strike may be explainable due to different reasons, but
      it is not ethically justifiable beyond any doubt. The health profession that is
      not prepared to give up strikes as gremial pressure tool, should not choose a
      profession that takes care of the ill. The best way to avoid medical strike is to
      prevent them: the society and the authority have the ethical obligation to create
      work conditions that elude conflicts. To settle disputes between physicians and
      health institutions, the creation of a permanent arbitral instance agreed by
      physicians and the authority, i.e. a high level committee integrated by respected
      individuals and physicians, could be necessary. This committee should send forth
      veredicts that would be obeyed by the contending parties.

PMID- 9138379
TI  - [Health care reform in Chile].
AB  - This is a document presented to the Chilean Academy of Medicine by the Health
      Minister, the economist Carlos Massad, First of all, he refers to the general
      context of the reform, that he considers a process and not a breakpoint.
      Afterwards, he enumerates the change task: a) to generate awareness of the change
      and to convert health in a State issue; b) to adequate programs to population's
      new health profile; c) to install new management instruments in the health
      system; d) to decentralize decisions and to promote the participation of
      beneficiaries; e) to establish incentives and to flexibilize the Health System
      and f) to introduce correctives to private health insurance. He believes that
      Chile must drift to a economical protection system for universal and solidary
      health events. The additional assurances that people wants to buy, must be
      delimited.

PMID- 9138380
TI  - [Hernan Iturriaga Ruiz, M.D., President of the Medical Society of Santiago, 1995
      1997].
AB  - Dr. Hernan Iturriaga is now President of Sociedad Medica de Santiago (Chilean
      Society of Internal Medicine) for the period 1995-1997. He received his M.D.
      title at the University of Chile in 1961 and his postgraduate training included a
      USPHS International Postdoctoral Research Fellowship at Mount Sinai School of
      Medicine (1966-1968) with Professors Hans Popper and Fenton Schaffner. He gained
      international reputation for his clinical and experimental studies on the effects
      of ethanol in the liver. Since 1982 he is Professor of Medicine at the University
      of Chile School of Medicine and in 1995 he became Director of the Chilean
      Japanese Institute for Digestive Diseases.

PMID- 9138381
TI  - [Pharmacokinetics, metabolism and pharmacovigilance].

PMID- 9138382
TI  - [Contribution of in vitro models to the management of hematologic risk in
      pharmacovigilance].
AB  - The decisions of health authorities concerning adverse effects of drugs are
      usually notified following clinical observations, but are rarely associated to
      experimental data. The haematopoietic tissue is one of the most sensitive to
      these effects. In order to anticipate and to explain adverse effects, it becomes
      necessary to carry out in vitro assays on normal human haematopoietic
      progenitors. We had the opportunity to use human cord blood progenitors which are
      able to repopulate allogeneic aplastic bone marrow. Many advantages are
      associated with this model: numerous samples, non-invasive, absence of species
      bias, possibilities of mechanistic approach. The clonogenic potential of
      progenitors in soft agar, as well as their ability to expand in liquid medium
      after stimulation with specific growth factors, have been used. Evidence of dose
      related toxicity by inhibition of colony formation or proliferation was analysed
      in the presence of reference molecules. Results were reproducible despite an
      intrinsic variability of progenitor density between samples. They were comparable
      to assays on bone marrow progenitors reported by us and others. Comparison of
      toxicity thresholds with plasma therapeutic ranges showed the potential risk for
      some molecules tested.

PMID- 9138383
TI  - [Management of cutaneous risk in pharmacovigilance: metabolic predisposition to
      Stevens-Johnson syndromes and toxic epidermal necrolysis].

PMID- 9138384
TI  - [Example of active therapeutic follow-up: itraconazole].
AB  - The systematic fungal infections are very serious diseases, the crude mortality
      in invasive aspergillosis reaches 75 to 100 per cent. Systemic mycosis tends to
      develop in immunocompromised patients with subsequent physiopathological state,
      causing a risk of impairment in their digestive absorption potential; in addition
      these patients are polymedicated and the emergence of multiple drug interactions
      is frequent. Itraconazole is a very potent antifungal drug with large safety
      margin and the drug monitoring to maintain a satisfactory plasma level.
      Immunocompromised patients with suspected malabsorption and treated with oral
      capsule itraconazole were monitored during two years. In such difficult patients
      (approximately equal to 500 cases), the result has shown good trough steady-state
      plasma levels in 72 per cent and insufficient in 28 per cent of the observed
      patients. However concomitant treatments with antacids produce, in a lot of cases
      (approximately equal to 48 per cent), a noticeable decrease of the itraconazole
      availability for these patients. A training program was established to perform
      the analytical determination of itraconazole and hydroxyitraconazole in
      biological samples by HPLC method. Analytical validation procedures were
      associated to this training program which included 115 scientific, technical
      staff (pharmacists, biochemists ...) from 56 hospitals and institutes.

PMID- 9138385
TI  - [Acute drug-induced agranulocytosis: experience of the Regional Center of
      Pharmacovigilance of Lyon over 7 years].
AB  - Sixty-two cases of drug-induced agranulocytosis, spontaneously reported to the
      regional drug monitoring centre in Lyon from 1988 to 1994, have been analysed.
      The mean age of patients was 58.6 years, and sex ratio was 1:1. The mean delay of
      onset was 46.2 days and absolute neutrophil counts (ANC) dropped below 0.1 x
      10(9)/l in 73 per cent of patients. Bone marrow aspirates disclosed absence of
      myeloid series in 28 per cent of investigated cases. Neutrophil recovery occurred
      after a mean of 9.3 days, and the overall fatality rate was 6.5 per cent.
      Haematopoietic growth factors (HGF) were used in 11 patients with an ANC below
      0.1 x 10(9)/l and/or a hypoplastic bone marrow. We have found no clear indication
      for a potential benefit of HGF treatment, but HGF were usually administered late
      during the course of neutropenia, i.e., after a mean of 6 days. The incidence
      rate estimated for people living in the Rhone administrative division was 3.3 per
      million per year, similar to that found in epidemiological studies. Drugs most
      frequently involved were anti-infective agents and psychotropic drugs.

PMID- 9138386
TI  - [Acute kidney failure secondary to intravenous immunoglobulin administration. 4
      cases and review of the literature].
AB  - Intravenous immunoglobulin (IVIG) is currently used for an increasing number of
      indications where an immune-medicated disorder is suspected. It is considered as
      a safe and efficacious treatment but several cases of severe acute renal failure
      (ARF) have been described since 1987. We report four cases of IVIG-induced ARF
      and the literature on the subject is reviewed. The chronological and semiological
      characteristics of this rare adverse effect are analysed. A sudden and marked
      increase of serum creatinine within the 2 to 4 days following institution of IVIG
      therapy, especially when the patient becomes oligo-anuric, is very suggestive of
      IVIG renal toxicity. The recovery of renal function is often obtained in 10 to 15
      days after discontinuation of the drug. Histological changes are characterized by
      osmotic nephrosis injuries. Patients generally presented numerous risk factors
      such as over 65 years, particularly in men, pre-existing renal disease, long
      standing diabetes mellitus or hypertension, volume depletion, quick infusion
      rate, body-weight adjustment of IVIG doses in fat subjects. The mechanism of
      renal injury remains speculative but an oncotic overloading of kidney probably
      occurs. These results indicate the need for research and investigation of risk
      factors before starting IVIG therapy. Close monitoring of serum creatinine and
      diuresis should be carried out during and after treatment.

PMID- 9138387
TI  - [Acute methotrexate poisoning: apropos of 16 cases reported to the Paris Poison
      Control Center and review of the literature].
AB  - 16 cases of acute methotrexate (MTX) poisoning were reported to the Paris Poison
      Control Centre and 62 others were published between 1974 and 1995. Until 1992,
      MTX was mainly prescribed for neoplastic diseases. Clinical features involve
      acute renal failure, pancytopenia, and cutaneous or mucous injury. These cases
      emphasise major risk factors responsible for misuse and overdosage. Since 1992,
      MTX has been increasingly used in rheumatological or pulmonary diseases
      (rheumatoid arthritis, steroid-dependent asthma). Most of the overdosages were
      due to a medical misuse (in the dosage regimen or a misunderstanding of the
      prescription by nurse, pharmacist or patient). All patients had a bone marrow
      suppression. The treatment is based especially on early administration of folinic
      acid rescue.

PMID- 9138388
TI  - [Clomiphene-exposed pregnancies--analysis of 39 information requests including 25
      cases with known outcome].
AB  - With the up to date published data, the risk of clomiphene exposure during
      pregnancy cannot be determined. After a review of animal experimentation results,
      we will discuss the human data. Most of the publications with human exposition
      concern treatments given before the beginning of pregnancy. The questions
      addressed to the Centre de Pharmacovigilance of Paris F. Widal will be detailed.
      From May 1983 to July 1995 39 requests are available with only 25 cases of known
      outcomes. For these 25 cases, five elective terminations and three spontaneous
      abortions are reported. Only one defect was observed among the 17 births (9
      females, 8 males): unilateral fibula agenesis the imputability of which is
      difficult to establish. These data seems reassuring; however, the number of
      patients studied is small. Other studies on clomiphene-exposed pregnancies are
      necessary in order to investigate this risk.

PMID- 9138389
TI  - [Simvastatin and pregnancy].
AB  - This study concerns 169 women whose exposure to simvastatin (Zocor or Lodales)
      during pregnancy led to a request for information from pharmaceutical firms. The
      evolution of pregnancies (among which 2 were twins) was documented in 125 women:
      66 women gave birth to normal babies, 40 requested and induced abortion, 12
      spontaneous abortions occurred, and the 9 other known pregnancy issues were 4
      premature newborns, 3 newborns with malformations and 2 fetal deaths. Apart from
      the 5 retrospective files concerning 5 spontaneous abortions, all the files were
      analysed prospectively. Except for induced abortions, regarding the prospective
      files, the pregnancy outcome was comparable with that of a general population.

PMID- 9138390
TI  - [Adverse effects related to the use of antitubercular drugs in psychiatric
      centers: retrospective study at the Philippe Pinel CH in Amiens 1994].
AB  - Management of tuberculosis in a hospital environment is well systematized and may
      include chemoprophylaxis, which may be hazardous when used in psychiatric
      impairments. We examined retrospectively adverse events occurring during a 6
      month period of antituberculosis treatment. Besides patients initially treated
      for active pulmonary tuberculosis, 16 other patients have benefited from
      chemoprophylaxis with isoniazid (INH) and/or rifampicin (RFP). All these patients
      (mean age 53 years) had been institutionalized for several years. Fifteen of them
      still received a mean of 5.4 +/- 2.2 drugs including 3.3 +/- 1.4 psychotropic
      agents. During antituberculous treatment, 5 patients (29 per cent) presented side
      effects: hyperuricaemia with pyrazinamide, neutropenia, dysphagia and anorexia,
      dizziness and falls, diabetes and fatal fulminant hepatitis associated with INH.
      Drug interactions were systemically searched for. Three probably led to clinical
      manifestations: they implicated INH with carbamazepine, RFP with theophylline and
      RFP with haloperidol. Our results suggest a greater sensitivity for adverse
      effects and drug interactions in psychiatric institutionalized patients. They
      pose the problem of the appropriateness of antituberculous chemoprophylaxis in
      such patients, particularly because of communication difficulties and
      polytherapy. The INH-RFP regimen should be avoided and the clinical and
      biological follow-up reinforced.

PMID- 9138391
TI  - [Prospective survey on adverse effects of radiopharmaceuticals].
AB  - In France, radiopharmaceuticals have been considered as drugs since 1992. Few
      adverse reactions with radiopharmaceuticals were described in the literature.
      Some authors have reported a rate of 1 to 6 reactions per 100,000 injections. The
      purpose of the present study was to evaluate the prevalence of
      radiopharmaceutical-induced side effects. A prospective survey was performed from
      November 1993 to May 1995 (during 18 months) in the Department of Nuclear
      Medicine of the University Hospital in Toulouse. There were 14,794 injections of
      radiopharmaceuticals (99mTc-phytate, 99mTc-microspheres of serum albumin, 99mTc
      dimercapto-succinic acid (DMSA), 99mTc-hydroxymethyldiphosphonate (HMDP), 99Tc
      colloid, 99mTc, 99mTc-sestamibi, Thallium-201). Three side effects were reported:
      one case of necrosis at the injection site, one case of vomiting and one case of
      dizziness. All the cases occurred with Tc99m-pyrophosphate. According to the WHO
      definition, the first side effect was classified as 'serious'. The causal
      relationship was unlikely for the first and second case and probable for the
      third. The outcome of these side effects was always favorable.

PMID- 9138392
TI  - [Periodic report of pharmacovigilance: new recommendations, results of a survey
      among 200 pharmaceutical laboratories].

PMID- 9138393
TI  - [Evaluation of declarations of severe adverse effects from the publication of the
      decree dated 13 March 1995 about the organisation of pharmacovigilance].

PMID- 9138394
TI  - [Pharmacoepidemiological study of methadone in a center of addiction management:
      adverse effects and combined drug consumption].

PMID- 9138395
TI  - [Acute urticaria, research of precise chronologic criteria].

PMID- 9138396
TI  - [Cough or asthma crisis induced by propylene glycol].

PMID- 9138397
TI  - [Apropos of a prospective systematic survey of pharmacovigilance in chemist's
      shops].

PMID- 9138398
TI  - [Homonymy of drugs: a cause of prescription and dispensing errors].
AB  - There have been recently a prescription error and a dispensing error in our
      department due to drug names which look or sound alike. Errors of this type have
      frequently been quoted in the Anglo-Saxon literature. The method of choosing a
      drug trade name is recalled, and a table of French drug names which can involve
      errors of prescription and dispensing errors is provided.

PMID- 9138399
TI  - Drugs inducing or aggravating parkinsonism: a review.
AB  - Drug-induced parkinsonism (DIP) is frequent. The list of drugs able to induce
      parkinsonism is long and probably incomplete, because new drugs, with previously
      unknown antidopaminergic activity, are constantly being added. Not all the drugs
      have the same potency for inducing parkinsonism. We classify these drugs in three
      groups: (1) drugs with obvious antidopaminergic activity which regularly induce
      parkinsonism; (2) drugs able to induce parkinsonism in particular individuals and
      (3) drugs which may aggravate Parkinson's disease treated with levodopa. The
      reports of isolated cases of parkinsonism induced by widely-used drugs (drugs in
      group 2) may be the result of either an idiosyncratic side effect or a
      misdiagnosis of parkinsonism. The antidopaminergic activity of the drugs of this
      group is weak and not sufficiently demonstrated. Maybe, in these cases, the
      blockage of other neurotransmitters different from dopamine plays a role in the
      induction of parkinsonism. Probably, the number of patients with DIP is higher
      than reported or detected, because many patients suffer from weak symptoms that
      quickly disappear after drug withdrawal. One of the main points of interest is
      knowing the list, because all these drugs, specially those of group 1, should be
      avoided or used with caution in the treatment of some common symptomatic problems
      in patients with Parkinson's disease, such as depression, arterial hypertension,
      diabetes mellitus and cardiac disorders. The precautions should extent to other
      populations especially susceptible to suffer from DIP, such as the elderly or
      patients with other neurodegenerative disorders, such as Alzheimer's disease.

PMID- 9138400
TI  - [Joint program of pharmacovigilance in Quebec: comparison with France, Aquitaine
      and the Basque region].
AB  - The Joint Pharmacovigilance Program in the province of Quebec was initiated by
      academic and professional bodies to serve since 1986 as a Regional Center for
      drug adverse reaction spontaneous reports. The contents of its database are
      compared with those of France, the Aquitaine Region around Bordeaux and the
      Basque country in Spain, recently presented in Therapie. The similarity of some
      data is striking: two thirds of reported adverse effects are already labeled;
      fatal reactions account for 2%; the female/male ratio is > 1 and reaches 2 in
      patients aged > 74 years. The nature of reporters does however show some
      differences; 57% of Quebec reports originate from pharmacists (90% in hospitals),
      against 0.8% in Aquitaine and 3.3% in the Basque. Specialists provide 21% of
      reports in Quebec but are responsible for 63% in France. These discrepancies may
      be explained by organisational differences in professional practice. A comparison
      of the signal generating values of reports in the French system would be both
      interesting and feasible.

PMID- 9138401
TI  - [Evaluation by poison control centers of minaprine from the modification of
      tablet dosages].
AB  - By 1990, the Clin Midy (SANOFI) laboratory had modified the dose of Cantor
      tablets: the content of active drug (minaprine) increased (50 to 100 mg).
      Therefore, acute intoxication by minaprine can be serious, with generalized
      seizures, resisting the classic treatment. We tried to evaluate the possible
      consequences of this change of dose for the gravity of suicide attempts. 1091
      voluntary acute intoxications have been collected by the national French Poisons
      Centres data bank, 226 of them by the Poisons center of Marseilles. We have
      compared, by the chi 2 method, the frequencies of seizure and death, before and
      after 1990. Results are significant, confirming an increased gravity of these
      intoxications since the modification of dosage. Then, the laboratory reduced the
      number of tablets per box. We don't know if this measure will be efficient.

PMID- 9138402
TI  - [Observation of illicit or misused psychotropic drugs (O.P.P.I.D.U.M.): five
      years of surveillance of products consumed by drug addicts at Marseille].
AB  - The aim of O.P.P.I.D.U.M. is the survey of products used by drug addicts. A five
      year survey, based on regular pools, has provided interesting results. 1,283
      patients (80 per cent men, about 27 years old, 1/4 employed) used 2,241 drugs.
      The most frequent was heroin, followed by benzodiazepines, cannabis and cocaine.
      Flunitrazepam was the most commonly misused product, taken by users who started
      consumption earlier, with a higher rate of unemployment and imprisonment. Cocaine
      was as often taken intravenously as by sniffing, and most often used before
      imprisonment. Ecstasy (M.D.M.A.) has appeared recently. Codeine taken alone was
      used by subjects older than the heroin users, more frequently employed and
      virtually never prison inmates: this suggests the existence of an unofficial
      detoxication and substitution process. Confidence of clinicians needs anonymity
      of the records and return of information. Such a campaign is about to be
      launched.

PMID- 9138404
TI  - [Metaclopramide and depression: apropos of a case of a pregnant women].

PMID- 9138403
TI  - [Risk of heavy precipitation of vancomycin in the presence of fluid gelatin in
      infusion tubes].

PMID- 9138405
TI  - Quinolones-induced acral erythema.

PMID- 9138406
TI  - [Prevalence of adverse effects of peripheral vasodilator agents in the elderly
      over the age of 65 years].

PMID- 9138408
TI  - [Hepatic fibrogenesis].
AB  - The hepatic extracellular matrix is involved in both the stability of liver
      architecture and the hepatic function. Fibrogenesis occurs during various chronic
      liver diseases. It is the consequence of an imbalance between synthesis,
      deposition and degradation of extracellular matrix components leading to fibrosis
      and, then, cirrhosis. Hepatic stellate cells are the main source of extracellular
      matrix components in fibrogenesis. Among the factors involved in fibrogenesis,
      transforming growth factor beta 1 plays a central role. The vascular and cellular
      consequences of liver fibrogenesis require new specific diagnostic and
      therapeutic strategies.

PMID- 9138407
TI  - [Anaphylactic reaction to ketoconazole].

PMID- 9138409
TI  - [Diagnosis of cirrhosis in adults].
AB  - The diagnosis of cirrhosis relies on the histological analysis of a liver sample
      provided by biopsy made by transparietal or transjugular route according to the
      haemostasis of the patient. The histological study allows also to characterize
      the causative process and the severity of the disease. In the absence of
      histological proof a high probability of cirrhosis could be assumed when a firm
      liver with a narrow inferior edge is associated or not with signs of hepatic
      failure or portal hypertension. The most common causes of cirrhosis in France are
      alcohol abuse, C and B viruses, genetic haemochromatosis, chronic active
      autoimmune hepatitis, primary biliary cirrhosis. The prevalence of viral causes
      is increasing.

PMID- 9138410
TI  - [Ascites complicating cirrhosis].
AB  - Cirrhotic ascites is the consequence of excessive water and sodium reabsorption
      by the kidney; due to portal hypertension, the fluid localises in the peritoneal
      cavity. The cause of the renal anomaly is hepatic failure. Occurrence of ascites
      in cirrhosis indicates poor prognosis and the need to consider transplantation.
      Echographic signs of ascites are sensitive and specific. Infected ascites is
      diagnosed on the basis granulocyte count increased over 250/microL. Treatment
      consists of a salt-free diet and diuretics, and of evacuation by puncture while
      avoiding induction of hypovolaemia.

PMID- 9138411
TI  - [Digestive hemorrhage in cirrhosis].
AB  - Variceal bleeding is the second cause of death in cirrhosis. To achieve
      haemostasis, sclerotherapy (or banding) is the first line treatment but
      vasoactive drugs (terlipressin or somatostatin) are an alternative and even a
      complement. Porto-systemic shunt is to be rapidly considered if a second
      endoscopic treatment has failed. Primary prevention lies on beta-blockers
      (propranolol or nadolol). Organic nitrates are an alternative and even a
      complement. Secondary prevention lies on banding or sclerotherapy; beta-blockers
      are an alternative and even a complement.

PMID- 9138412
TI  - [Etiological treatment of cirrhosis in adults].
AB  - Etiological treatment is based upon: abstinence in case of alcoholic cirrhosis;
      alpha-interferon in case of B or C viral cirrhosis; corticosteroids in case of
      autoimmune cirrhosis; ursodeoxycholic acid in case of primary biliary cirrhosis;
      stopping the drug in case of drug-induced cirrhosis; surgery in case of secondary
      biliary cirrhosis; venesections in case of genetic haemochromatosis; liver
      transplantation in cases of Wilson's disease and alpha 1-anti-trypsin deficiency.
      Overall, these treatment are more effective when undertaken early in the course
      of the liver disease.

PMID- 9138413
TI  - [Management of non-complicated cirrhosis].
AB  - Diagnosis of compensated cirrhosis can be confirmed by needle liver biopsy. This
      may give a clue to the aetiology and activity of the disease. All patients with
      cirrhosis underwent upper gastrointestinal endoscopy and abdominal
      ultrasonography. Treatment with non selective beta-blockers in patients with
      large esophageal varices is strongly recommended. Endoscopic screening every year
      in patients with small varices and every other year in patients without varices
      is considered appropriate to identify patients at risk of bleeding. Patients with
      hepatic cirrhosis are at an increased risk of developing primary malignant
      tumours of the liver. Screening includes abdominal ultrasound and determination
      of serum alpha-faetoprotein every 6 months. Bacterial infections can be a severe
      complication in cirrhotic patients. They must be detected early and treated.
      Several drugs are contra-indicated in these patients.

PMID- 9138414
TI  - [Hepatic transplantation for cirrhosis].
AB  - Cirrhosis accounts for 60% of liver transplantations that are performed. The main
      causes are chronic viral hepatitis B and C, and alcoholism. However, all patients
      with severe cirrhosis are potential candidates for liver transplantation,
      regardless of the cause. Liver transplantation is indicated when the patient's
      life expectancy is one year or less. The main criterion for transplantation is
      severe liver failure (Child-Pugh's stage C). Transplantation is also proposed in
      patients with intractable ascites, and in patients with spontaneous
      encephalopathy. Isolated portal hypertension is not an indication for
      transplantation. Liver transplantation in hepatocellular carcinoma is still a
      matter of debate. The results of liver transplantation are very satisfactory with
      survival rates of 70% at 5 years and patient rehabilitation is usually excellent.

PMID- 9138415
TI  - [Cirrhosis in children].
AB  - Chronic cholestasis, starting early in life, inborn errors of metabolism and
      chronic hepatitis are the main causes of cirrhosis in children. Precise
      identification of the cause is crucial because effective therapy is available for
      many of them. Close follow-up is necessary for all the child's life to prevent,
      detect and manage the complications and to decide on liver transplantation when
      no effective therapy is available. Results of liver transplantation in children
      with cirrhosis indicate that close to 80% of children will be alive 10 years
      after surgery. Liver transplantation must be carried out before signs of liver
      failure are present.

PMID- 9138416
TI  - [Pancytopenia. Diagnostic orientation].

PMID- 9138417
TI  - [Prescription of vascular loading solution].

PMID- 9138418
TI  - [Hematuria (macroscopic and microscopic in adults and children). Diagnostic
      orientation].

PMID- 9138419
TI  - [Schizophrenic syndromes. Diagnosis, course, treatment].

PMID- 9138420
TI  - [Pain. Therapeutic methods and strategies].

PMID- 9138421
TI  - [Diabetic retinopathy. Physiopathology, diagnosis, course, prognosis, treatment].

PMID- 9138422
TI  - Dodecylglycerol provides partial protection against glutamate toxicity in
      neuronal cultures derived from different regions of embryonic rat brain.
AB  - Primary cultures enriched in neurons dissociated from embryonic rat cerebral
      cortex, cerebellum, or hippocampus were treated in a chemically defined serum
      free media with either vehicle, dodecylglycerol (DDG, 3 microM), or glutamate (75
      microM), or preincubated with DDG for 4 or 24 h, and further incubated with
      glutamate. Their morphological and biochemical assessments (lactate dehydrogenase
      [LDH] release in the culture media, neuronal viability and intracellular Ca2+
      mobilization) were made. Neurotoxic effects of glutamate and glutamate-mediated
      increases in intracellular Ca2+ were maximal in neurons from cerebellum and
      minimal in neurons from cortex. Cotreatment of cells with DDG and glutamate
      failed to provide significant neuronal protection against glutamate in the three
      brain regions. Pretreatment of cells with DDG for 4 or 24 h prior to glutamate
      treatment provided significant neuroprotection as judged by morphological changes
      and a decrease in LDH activity. Neuroprotection of approximately 15-35% was
      observed following 4 h of DDG pretreatment, increasing to 60-85% protection after
      24 h of DDG pretreatment. Although the mechanism of DDG's neuroprotective action
      remains to be elucidated, these results demonstrate that both glutamate and DDG
      have differential specificity for anatomical regions of the brain.

PMID- 9138423
TI  - Brain-derived neurotrophic factor suppresses programmed death of cerebellar
      granule cells through a posttranslational mechanism.
AB  - Cerebellar granule cells isolated from 7-d-old rats have been shown to die in
      vitro unless they are continuously exposed to elevated K+ (25 mM). Here we have
      characterized this neuronal death, and examined whether its major features are
      shared with those of sympathetic neurons following nerve growth factor (NGF)
      deprivation. Granule cells underwent active cell death accompanied by
      morphological features of apoptosis. Brain-derived neurotrophic factor (BDNF),
      but not NGF, was capable of preventing this neuronal death by acting
      posttranslationally. Moreover, semiquantitative RT-PCR, Northern blot, and
      immunoblot analyses showed that trkB, the signal-transducing receptor for BDNF,
      was upregulated during neuronal death of granule cells in vitro. These results
      extend recent findings for the role of BDNF in granule cell development, and
      suggest that BDNF plays a pivotal role on the regulation of the neuronal
      death/survival of granule cells.

PMID- 9138424
TI  - Inhibition of nitric oxide synthase potentiates hypertension and increases
      mortality in traumatically brain-injured rats.
AB  - We examined the effects of N omega-nitro-L-arginine methyl ester (L-NAME), an
      inhibitor of nitric oxide synthase (NOS), on mortality, morbidity, and
      cardiovascular parameters following traumatic brain injury (TBI) in the rat. Rats
      were anesthetized with 2% isoflurane prior to moderate (2.0 atmosphere), central
      fluid percussion TBI. Temporalis muscle temperature was maintained at 37 +/- 0.5
      degrees C. L-NAME (10 mg/kg iv) was administered once at either 5 min before, 5
      min after, or 15 min after TBI. Sensorimotor deficits and spatial learning/
      memory deficits were assessed after injury. Separate groups of rats were
      monitored for cardiovascular parameters. Preinjury administration of L-NAME
      significantly increased mortality from 13 (vehicle) to 70% (associated with
      pulmonary edema), whereas postinjury, L-NAME had no effect on mortality (14 and
      25%). L-NAME administered at 5 or 15 min after injury had no significant effect
      on motor performance or cognitive performance deficits associated with TBI. L
      NAME in uninjured rats increased arterial blood pressure by 25 mmHg within 2 min.
      L-NAME injected 5 min before TBI greatly prolonged the hypertensive episode
      associated with TBI (1 min in vehicle vs 60 min in L-NAME). L-NAME injected 5 min
      after TBI caused a sustained 35 mmHg increase in blood pressure. These findings
      suggest that acute inhibition of NOS has detrimental consequences on mortality
      that may be owing to its cardiovascular effects.

PMID- 9138425
TI  - Aberrant expression of the constitutive endothelial nitric oxide synthase gene in
      Alzheimer disease.
AB  - Neuritic pathology is a major neuroanatomical correlate of dementia in Alzheimer
      disease (AD). Nitric oxide (NO) is linked to neuritic growth and synaptic
      plasticity. Expression of one of the enzymes responsible for NO synthesis, the
      constitutive endothelial NO synthase (ceNOS), was investigated in brains of AD
      and Down syndrome patients using RNase protection assays, in situ hybridization,
      and immunocytochemistry. In end-stage AD, ceNOS expression was reduced in
      cortical neurons, and the enzyme was aberrantly translocated to membranes of
      proliferated swollen or collapsed neuritic processes. In addition, ceNOS
      expression was strikingly increased in glial cells characterized mainly as
      protoplasmic (Type 2) astrocytes, which are responsible for maintaining the
      structural and functional integrity of cell processes in the CNS. In Down
      syndrome, similar abnormalities emerged by the third decade, preceding the
      cognitive decline and establishment of CERAD criteria for AD, indicating that
      aberrant ceNOS expression occurs early in the course of neurodegeneration. The
      results suggest that aberrant ceNOS translocation and gene regulation may have
      important roles in the pathogenesis of AD neuritic pathology.

PMID- 9138426
TI  - Synaptosomal iron-dependent lipid peroxidation inhibition after subarachnoid
      hemorrhage by lazaroid in vivo treatment.
AB  - The production of oxygen-free radicals and their subsequent peroxidative action
      on membrane unsaturated fatty acids could be enhanced after subarachnoid
      hemorrhage (SAH). We have studied the effects of the in vivo pharmacological
      treatment with a lazaroid (U78517F) after experimental SAH, on lipid peroxidative
      patterns in cortical synaptosomal preparations. U78517F is a lipid-soluble
      antioxidant with a potent action to inhibit iron-dependent lipid peroxidation.
      Experimental SAH was induced in anesthetized rats by slow injection of 0.3 mL of
      autologous arterial blood into cisterna magna. The hemorrhagic animals were
      treated with 5 mg/kg iv of U78517F immediately after surgical operation. The
      animals were sacrificed 1 d after the hemorrhage and the thiobarbituric acid
      reactive material (TBAR) was assayed in basal conditions and after 1, 3, 5, 10,
      and 20 min of incubation at 37 degrees C with a pro-oxidant mixture on three
      different rat groups: sham-operated (0.3 mL of mock cerebrospinal fluid (CSF)
      into cisterna magna), hemorrhagic (0.3 mL of autologous arterial blood into
      cisterna magna), and hemorrhagic-treated. The hemorrhagic event did not influence
      the membrane lipoperoxidation levels in basal conditions, whereas peroxidative
      stimulation in vitro caused significant increases in hemorrhagic animals compared
      to the sham-operated, and in hemorrhagic-treated animals, the synaptosomal TBARs
      were similar to controls. The pharmacological treatment showed its effectiveness
      only following incubations with pro-oxidants; therefore, U78517F seems to be
      protective for membranes in case of severe lipid peroxidative stress.

PMID- 9138427
TI  - Global cerebral ischemia and reperfusion alters NMDA receptor binding in canine
      brain.
AB  - We employed a canine model to test whether binding to the N-methyl-D-aspartate
      (NMDA) class of glutamate receptor channels is altered by global cerebral
      ischemia and/or reperfusion. Ischemia was induced by 10-min cardiac arrest,
      followed by restoration of spontaneous circulation for periods of 0, 0.5, 2, 4,
      and 24 h. In vitro autoradiography was performed on frozen brain sections with
      three radioligands: [3H]glutamate (under conditions to label the NMDA site),
      [3H]glycine, and [3H]MK-801. Modest decreases in [3H]glutamate and [3H]MK-801
      binding were seen in several regions of hippocampus, and parietal and temporal
      cortex at early times after reperfusion, with values returning toward control by
      24 h. In the striatum, a different pattern was seen: [3H]glutamate and [3H]MK-801
      binding increased 50-200% at 0.5-4 h after the start of reperfusion, returning
      toward control levels by 24 h. These increases correlate with findings of
      increased sensitivity to NMDA-stimulated release of dopamine from striatal tissue
      in the same model (Werling et al., 1993), and suggest that changes in tissue
      receptors may contribute to the selective vulnerability to ischemic damage during
      the first hours following reperfusion.

PMID- 9138428
TI  - Alterations of excitatory amino acid receptors in the brain of manganese-treated
      mice.
AB  - An excessive activation of excitatory amino acid (EAA) receptors has been
      associated with oxidative stress, which is considered the primary cause of
      manganese (Mn) poisoning neurotoxicity. Therefore, the EAA receptor distribution
      was analyzed by autoradiographic methods in several brain regions during Mn
      intoxication. We found that chronic treatment of mice with MnCl2 during 8 wk
      significantly alters the L-[3H]glutamate (L-[3H]Glu) binding to total glutamate
      (Glu) receptors, as well as to N-methyl-D-aspartate (NMDA) and quisqualate (QA)
      receptor subtypes. A generalized decrease of 16-24% of the L-[3H]Glu binding to
      total Glu receptors was found in all cortex, hippocampus, basal ganglia (except
      globus pallidus), and cerebellum. Saturation studies showed a significant
      reduction of the maximal number of receptors (Bmax) in Mn-treated mice, whereas
      the affinity (Kd) was not altered. L-[3H]Glu binding to NMDA sites was mainly
      decreased (10-21%) in a few cortical regions, basal ganglia (except globus
      pallidus), and hippocampus, whereas binding to QA receptor subtype was diminished
      (16-30%) in cortex, hippocampus, and cerebellum. The decrease of Glu receptor
      binding sites during Mn poisoning could reflect a receptor downregulation more
      than neuronal loss, since these reductions are moderate and diffuse. Thus, this
      down-regulation might mean a protection mechanism against an excitotoxic process
      associated with Mn toxicity.

PMID- 9138429
TI  - Granule cell mRNA levels for BDNF, NGF, and NT-3 correlate with neuron losses or
      supragranular mossy fiber sprouting in the chronically damaged and epileptic
      human hippocampus.
AB  - This study determined in temporal lobe epilepsy patients if there were
      correlations among hippocampal granule cell expression of neurotrophin mRNAs,
      aberrant supragranular mossy fiber sprouting, and neuron losses. Consecutive
      surgically resected hippocampi (n = 9) and comparison tissue from autopsies (n =
      3) were studied for: 1. Granule cell mRNA levels using in situ hybridization for
      brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and
      neurotrophin-3 (NT-3); 2. neo-Timm supragranular mossy fiber sprouting; and 3.
      Ammon's horn neuron densities. Clinically, patients were classified into those
      with hippocampal sclerosis (HS; n = 7) and non-HS cases (i.e., mass lesions and
      autopsies; n = 5). Results showed that compared to non-HS cases, HS patients
      showed increased granule cell mRNA levels for BDNF, NGF, and NT-3 (p = 0.035, p =
      0.04, p = 0.045 respectively; one-tail directional test). Moreover, granule cell
      BDNF mRNA levels correlated inversely with Ammon's horn neuron densities (p =
      0.02) and correlated positively with greater supragranular mossy fiber sprouting
      (p = 0.02). NGF mRNA levels correlated inversely with Ammon's horn neuron
      densities (p = 0.02), and NT-3 mRNA levels correlated inversely with age at
      surgery (p = 0.04) and correlated positively with greater mossy fiber sprouting
      (p = 0.026). These results indicate in the chronically damaged human hippocampus
      that granule cells express neurotrophin mRNAs, and mRNA levels correlate with
      either hippocampal neuron losses or aberrant supragranular mossy fiber sprouting.
      These data support the hypothesis that in the epileptic human hippocampus, there
      may be pathophysiologic associations among mossy fiber synaptic plasticity,
      hippocampal neuron damage, and granule cell mRNA neurotrophin levels.

PMID- 9138430
TI  - Presence of functional NMDA receptors in a human neuroblastoma cell line.
AB  - Data are presented that provide convincing evidence for the expression of
      structurally normal and functional NMDA receptors by acetylcholine-producing
      human LA-N-2 neuroblastoma cells in culture. Reverse transcription and polymerase
      chain reaction (RT-PCR), followed by cloning and DNA sequencing, revealed the
      presence in these cells of mRNA representing the key subunit, NMDAR1, of the
      receptor. This mRNA was further demonstrated by Northern analysis to be the same
      size as that described for human neurons. The neutral red cytotoxicity assay was
      utilized to examine the influence on these neuroblastoma cells of a 48-h
      incubation with either L-glutamic acid or the specific NMDA agonist N-phthalamoyl
      L-glutamic acid (NPG). Cell cytotoxicity was shown by this assay to be increased
      through incubation with glutamate at 1 and 10 mM by 27 and 37%, and through
      incubation with NPG at 0.1 and 1 mM by 28 and 46%. A possible mechanism of these
      toxic effects was further evaluated using the whole-cell configuration of the
      patch-clamp technique and the specific NMDA agonists (+/-)1-aminocyclobutane-cis
      1,3-dicarboxylic acid (ACDA) and NPG. Using this procedure, a voltage-dependent
      tetrodotoxin-sensitive inward sodium current was found to be increased (x 1.5) by
      L-glutamic acid and by both NMDA agonists in the presence of glycine. Another
      voltage-gated inward current, probably carried by calcium ions, was increased
      three- to fourfold. Hence, these glutamate activities observed in human LA-N-2
      neuroblastoma cells appear to occur through the activation of functional NMDA
      receptors in much the same way as reported for neurons, and both glutamate and
      NMDA agonists can be toxic to these neuroblastoma cells. Our findings, therefore,
      suggest this cell line will provide a model suitable for investigating the
      mechanisms of NMDA-related long-term potentiation (LTP) in neurons and of the
      NMDA-related neurotoxic effects of glutamate in disease states that involve a
      reduction in cholinergic function.

PMID- 9138431
TI  - Limited junctional diversity of V delta 5-J delta 1 rearrangement in multiple
      sclerosis patients.
AB  - T-cell receptor (TCR) delta gene repertoire, as assessed by V delta-J delta
      rearrangements, has been analyzed in nine multiple sclerosis (MS) cases and in 30
      healthy individuals by seminested PCR technique. Among the V delta-J delta
      junctional diversities studied, the most striking result has been observed in V
      delta 5-J delta 1 rearrangement. The detection of repeated V delta 5-J delta 1
      nucleotide sequences in all analyzed clones from seven out of nine patients
      studied proved the monoclonal nature of gamma delta T-cells with V delta 5-J
      delta 1 rearrangement. The clonal nature of this rearrangement proved by PAGE and
      sequencing analysis may suggest an antigen-driven expansion of gamma delta T
      cells and argues for a significant role of gamma delta T-cells with V delta 5-J
      delta 1 rearrangement in MS pathogenesis. However, it cannot be excluded that
      clonal expansion of these lymphocytes may represent secondary change to central
      nervous system damage.

PMID- 9138432
TI  - Summaries of break-out sessions.

PMID- 9138433
TI  - Medicine and the arts. Plane life.

PMID- 9138434
TI  - The effect of streptozotocin-induced diabetes on dopamine2, serotonin1A and
      serotonin2A receptors in the rat brain.
AB  - The effect of streptozotocin (STZ)-induced diabetes and a combination of chronic
      treatment with haloperidol (HPD) on dopamine (DA)D2, serotonin (5-HT) 5-HT1A and
      5-HT2A receptors was investigated in rat brain. Rats were randomly assigned to
      one of four groups: vehicle-vehicle, STZ-vehicle, vehicle-HPD, and STZ-HPD
      groups. Four weeks after single administration of STZ (65 mg/kg IV) or vehicle
      (citrate buffer), rats received depot HPD (4 mg/kg IM) or vehicle (sesame oil)
      once a week for 4 weeks. Sixteen days after the last injection of HPD or vehicle,
      rats were sacrificed, and the density of binding sites was determined using
      [3H]spiperone as ligand in the striatum (D2),[3H]8-hydroxy-2-(di-n-propyl)
      aminotetraline in the hippocampus (5-HT1A), and [3H]ketanserin in the frontal
      cortex (5-HT2A). The density of D2 receptors was significantly increased in the
      vehicle-HPD compared to vehicle-vehicle controls. However, striatal D2 receptor
      density of the STZ-HPD and the STZ-vehicle were not significantly different from
      the vehicle-vehicle group. A significant increase in cortical 5-HT2A receptor
      density was observed only in the group of STZ-vehicle. Treatment with STZ, HPD,
      or the combination thereof, did not affect the density of 5-HT1A receptors. The
      affinity constants for D2, 5-HT1A, and 5-HT2A receptors were not affected by any
      treatment. These results suggest that diabetic state may affect brain
      serotonergic activity via an increase in the density of 5-HT2A receptors. This
      may indicate an increased vulnerability to major depression in patients with
      diabetes. The lack of an effect of the combined chronic treatment with STZ and
      HPD on the D2 receptor density may correspond to the increased risk to develop
      tardive dyskinesia in patients with diabetes.

PMID- 9138435
TI  - Etiologic heterogeneity of the psychoses: is there a dopamine psychosis?
AB  - The distribution of drug-free plasma homovanillic acid (pHVA) concentrations was
      studied in a sample of psychotic patients, some of whom were selected for good
      prognostic features. Baseline pHVA was bimodally distributed, suggesting two
      different patient populations. The high-pHVA patients showed periods of better
      functioning and/or fewer symptoms 5 years before admission (p < .05) and had a
      more rapid (p < .05) and complete (p < .001) subacute neuroleptic response than
      lower-pHVA psychotics. High-pHVA psychotics did not differ in other aspects of
      demographics or clinical presentation from lower-pHVA psychotics. Compared to the
      general population, there were more psychotics in the families of high-pHVA
      patients (p < .005). Rapid antipsychotic response by high-pHVA psychotics is
      consistent with blockade of the effects of excess synaptic dopamine at D2
      receptors for these patients. Results are discussed in the context of the
      syndromic heterogeneity of the psychoses.

PMID- 9138436
TI  - The effect of decreased catecholamine transmission on ERP indices of selective
      attention.
AB  - This study examines the effect of decreased catecholamine transmission on event
      related potential (ERP) indices of selective attention. Intravenous clonidine
      (1.5 micrograms/kg Catapres), droperidol (15 micrograms/kg Droleptan), or placebo
      were administered to healthy adult males prior to performance of a
      multidimensional auditory selective attention task (SAT) in which dichotically
      presented sequences of tone pips varied on dimensions of location (left or right
      ear), pitch (high or low), and duration (short or long). Subjects were required
      to make a button press response to infrequent "target" stimuli that matched a
      prespecified stimulus on the three dimensions. ERPs were recorded during the
      task. Clonidine led to a significant increase of processing negativity (PN) over
      200-400 ms at the irrelevant location. Droperidol led to a significant increase
      in reaction time (RT), a significant decrease in hit rate, and an attenuation of
      PN over the 200- to 400-ms and 400- to 700-ms epochs. Neither substance led to a
      significant change in P3 amplitude. The role of catecholamines in the selective
      attention subprocesses of "tuning" and "switching" is discussed.

PMID- 9138437
TI  - Impulsive aggression in personality disorder correlates with platelet 5-HT2A
      receptor binding.
AB  - The purpose of this study was to examine the relationship between platelet 5-HT2A
      receptor binding and aggressive behavior. 125I-LSD Bmax and Kd values were
      measured for 22 subjects meeting DMS-III-R criteria for one or more personality
      disorders and 12 healthy volunteer subjects. Aggression and impulsivity were
      assessed using the Buss-Durkee Hostility Inventory (BDHI) Assault scale, Life
      History of Aggression (LHA) scale, and the Barratt-11 Impulsiveness scale (BIS
      11). Bmax and Kd values did not differ between personality disordered subjects
      and healthy volunteers. However, both Bmax and Kd values correlated positively
      with BDHI Assault scores in personality-disordered subjects but not in healthy
      volunteer subjects. These results suggest that assaultiveness in personality
      disordered subjects may covary with increasing numbers, but decreasing affinity,
      of platelet 5-HT2A receptor sites labeled by 125I-LSD.

PMID- 9138438
TI  - Adverse effects of risperidone on eye movement activity: a comparison of
      risperidone and haloperidol in antipsychotic-naive schizophrenic patients.
AB  - Risperidone is a novel and clinically effective atypical antipsychotic medication
      with a unique biochemical profile. To contrast the neurophysiological effects of
      this new medication with those of a typical antipsychotic medication, we
      performed quantitative measurements of saccadic eye movements in a series of
      antipsychotic-naive schizophrenic patients treated with either risperidone or
      haloperidol. Patients were tested before and after 1 month of treatment, and a
      matched group of healthy subjects was tested twice over a similar time interval.
      Risperidone, but not haloperidol, was associated with prolonged latency and
      decreased peak velocity and accuracy of saccadic eye movements that was
      detectable 4 weeks after treatment initiation. The adverse effects of risperidone
      may be due to the lack of development of acute tolerance to its powerful
      serotonergic (5-HT2A) antagonism, which could be responsible for the disruption
      of brainstem physiology in regions controlling saccadic eye movements.

PMID- 9138439
TI  - A comparison of the effects of intravenous pentagastrin on patients with social
      phobia, panic disorder and healthy controls.
AB  - The present study sought to determine whether social phobics, like patients with
      panic disorder, have increased sensitivity to the panicogenic effects of
      pentagastrin. Intravenous pentagastrin and placebo were administered in a double
      blind fashion to 19 social phobics, 11 patients with panic disorder, and 19
      healthy controls while they participated in a structured social interaction task.
      Behavioral, cardiovascular, and neuroendocrine responses were obtained.
      Pentagastrin led to panic attacks in 47% of the social phobics, 64% of the panic
      disorder patients, and 11% of the healthy controls. The social interaction itself
      increased anxiety, blood pressure, and pulse in all three groups. These findings
      suggest that the panicogenic effects of pentagastrin are not limited to patients
      with panic disorder and provide further evidence for shared neurobiology in
      social phobia and panic disorder.

PMID- 9138440
TI  - Increase in AP-1 transcription factor DNA binding activity by valproic acid.
AB  - Valproic acid (VPA), a simple branched fatty acid anticonvulsant, has been
      demonstrated to have clinical efficacy in the treatment of manic-depressive
      illness (Bowden et al., 1994), but the mechanism(s) by which VPA produces its
      therapeutic effects remain to be elucidated. VPA's clinical antimanic action
      require a lag period for onset and are not immediately reversed upon
      discontinuation of treatment, effects that suggest alterations at the genomic
      level; we therefore investigated the effects of VPA on the modulation of the DNA
      binding activity of key transcription factors. DNA binding activities of
      activator protein 1 (AP-1) and cAMP responsive element binding protein (CREB)
      were studied in acute (hours) and chronic (days) VPA-treated rat C6 glioma cells.
      VPA did not affect CREB DNA binding activity, but concentration- and time
      dependently increased AP-1 DNA binding activity. The activity was raised at 2
      hours (the shortest time examined) and remained high after 6 days (the longest
      time used) of continuing VPA treatment. VPA also enhanced AP-1 DNA binding
      activity in human neuroblastoma (SH-SY5Y) cells. Because the effects of VPA were
      markedly inhibited by cycloheximide, they appear to require new protein
      synthesis. Taken together, the data suggest that antimanic agents may affect gene
      expression by modulation of the activity of major transcription factors; in view
      of the key roles of these nuclear transcription regulatory factors in long-term
      neuronal plasticity and cellular responsiveness, these effects may play a major
      role in VPA's therapeutic efficacy and are worthy of further study.

PMID- 9138441
TI  - Characterization of the disruptions of prepulse inhibition and habituation of
      startle induced by alpha-ethyltryptamine.
AB  - Alpha-ethyltryptamine (AET), a monoamine oxidase inhibitor and potent monoamine
      releasing agent, has been sold illicitly as a substitute for the entactogen 3,4
      methylenedioxy-N-methylamphetamine (MDMA), and is the first example of an
      indolealkylamine analog demonstrated to substitute in MDMA-trained animals.
      Previous studies have demonstrated that MDMA and AET have similar effects on
      unconditioned motor behavior in rats. Furthermore, the locomotor-activating
      effects of both MDMA and AET are blocked by pretreatment with fluoxetine, a
      selective serotonin (5-HT) uptake inhibitor, suggesting that the two compounds
      may share a presynaptic mechanism of action. This study examined the effects of
      AET using measures of startle plasticity, specifically prepulse inhibition (PPI),
      and habituation. PPI, a measure of sensorimotor gating, is reduced in rats
      treated with hallucinogens, 5-HT releasers, and dopamine agonists. In contrast,
      startle habituation is reduced in rats treated with hallucinogens and 5-HT
      releasers. AET (1.25, 2.5, 5, and 10 mg/kg) decreased PPI of acoustic startle and
      reduced the habituation of tactile startle. To determine whether AET produces
      these effects via pre- or postsynaptic actions, fluoxetine (10 mg/kg) was used as
      a pretreatment. By itself, fluoxetine did not disrupt PPI, but did reduce startle
      habituation. Fluoxetine pretreatment prevented the AET-induced disruption of PPI
      and reduced the AET-induced disruption of startle habituation. Combined with
      previous findings, these results confirm that AET produces behavioral effects
      that mimic those of other indirect 5-HT agonists and that the effects of AET on
      startle plasticity are due to the release of presynaptic 5-HT.

PMID- 9138442
TI  - Analyses of HLA-DQ alleles in recurrent spontaneous abortion (RSA) couples.
AB  - PROBLEM: The influence of HLA sharing on pregnancy outcome is controversial. In
      renal transplantation, HLA-DQB1 donor-recipient mismatches have been shown
      beneficial for long-term transplant success. Since pregnancy is defined as
      Nature's allograft, we investigated the relevance of HLA-DQ mismatching in normal
      reproducing couples compared to couples experiencing RSA. METHOD: Unexplained RSA
      couples referred to our laboratory for immunological testing were classified by
      immunological findings and obstetrical history. Primary RSA couples shared > or =
      2 HLA-A, B, or DR antigens, had no cytotoxic anti-paternal antibodies, and no
      gestation beyond 20 weeks. Secondary RSA couples had cytotoxic anti-paternal
      antibodies and RSA after a live birth. HLA-DQA1 and DQB1 alleles were identified
      by PCR-SSP. RESULTS: No differences in DQA1 and DQB1 mismatch were observed among
      RSA patients and controls. DQA1-DQB1 haplotype mismatches were not different
      among the three groups of couples. CONCLUSIONS: In contrast to renal transplant,
      HLA-DQ incompatibility did not differ among RSA couples compared with successful
      reproducing couples.

PMID- 9138443
TI  - Phospholipid binding plasma proteins required for antiphospholipid antibody
      detection--an overview.
AB  - PROBLEM: Antibodies to phospholipid antigens (aPA) are associated with thrombosis
      thrombocytopenia and recurrent pregnancy loss. Contemporary data show many aPA
      target phospholipid-binding plasma proteins and not phospholipids. The purpose of
      this overview is to describe several phospholipid-binding proteins and provide
      data to demonstrate how the interaction between phospholipids and phospholipid
      binding proteins results in expression of neo-autoantigenic epitopes. METHOD:
      Review of existing data. RESULTS: Illustrations of how certain plasma proteins
      beta 2 glycoprotein I, prothrombin, high and low molecular weight kininogens
      interact with the anionic phospholipids cardiolipin and phosphatidylserine and
      the zwitterionic phospholipid, phosphatidylethanolamine are shown and discussed.
      A model of aPA mediated thrombosis is presented. CONCLUSIONS: Some aPA recognize
      phospholipids directly, however, the majority and many which correlate with
      pathology target phospholipid binding proteins. Published data indicate that aPA
      represent a constellation of antibodies with multiple specificities. Insight into
      mechanisms responsible for aPA-associated thrombosis should provide a basis for
      treatment.

PMID- 9138444
TI  - Sperm antigens and their use in the development of an immunocontraceptive.
AB  - PROBLEM: Overpopulation is a global problem of significant magnitude, with grave
      implications for the future. World population is predicted to reach 10 billion
      people by the year 2050, an increase of more than 75% over the current
      population. Development of new contraceptives is necessary, since current forms
      of birth control are unavailable to many individuals due to sociological,
      financial, or educational limitations. METHODS: In an effort to identify new
      contraceptive alternatives, sperm-specific antigens are under the investigation
      as the basis for immunological regulation of fertility through contraceptive
      immunization. Anti-sperm antibodies (ASA) inhibit sperm function in vitro, induce
      infertility in experimental models, and have been implicated in some cases of
      clinical infertility. Furthermore, the development of ASA in vasectomized men
      does not lead to physiological complications despite the persistence of these
      antibodies for years; thus, ASA induced by immunization of men and women may be
      similarly harmless. Immunization has several conceptual advantages as a method of
      fertility regulation. Employment of non-pharmacologically active agents,
      convenience of administration, low cost, and the potential for relatively long
      lasting yet reversible effects. RESULTS: Various approaches have been taken to
      identify candidate sperm antigens for immunocontraceptive development. Studies
      that utilized monoclonal antibodies and polyclonal antisera generated against
      sperm preparations have identified such promising candidates as PH-20, fertilin,
      SP-17, and SP-10. In animal model, 100% contraceptive effects were induced
      following PH-20 immunization and the effects were reversible. More recently, ASA
      from the sera of infertile patients were employed to identify several candidates
      as expressed by testis cDNA libraries. Perhaps the most extensively characterized
      and effective immunogen candidate identified thus far is lactate dehydrogenase-C4
      (LDH-C4). Active immunization with LDH-C4 suppressed fertility in a variety of
      mammalian species, including primates, and the reversibility of these effects was
      demonstrated. CONCLUSION: The successful results obtained thus far support the
      feasibility of an effective immunocontraceptive and indicate the importance for
      continued investigation of additional sperm antigens as contraceptive immunogen
      candidates.

PMID- 9138445
TI  - Induction of experimental antiphospholipid antibody syndrome in PL/J mice
      following immunization with beta 2 GPI.
AB  - PROBLEM: Immunization with beta 2-glycoprotein I (beta 2 GPI) induces
      antiphospholipid antibodies (aPL) in normal mice and rabbits. Recently we
      reported early onset of autoimmunity in MRL/(+2) mice following immunization with
      beta 2 GPI. There is a close association between aPL with thrombosis, recurrent
      fetal loss, and intrauterine growth retardation. In this study we evaluated the
      effect of beta 2 GPI-induced aPL on pregnancy outcomes in an inbred strain of
      mice (PL/J). METHOD: Three groups of seven-week female PL/J mice (12 per group)
      were studied. Group A was immunized with beta 2 GPI and group B with ovalbumin;
      group C was not not immunized. After two booster injections, the mice were tested
      for aPL, anti-DNA by ELISA, and for ANA by indirect immunofluorescence. Platelet
      count and pregnancy outcomes were studied at the age of 14 weeks. RESULTS: The
      aPL and anti-DNA levels were higher at 12 and 14 weeks in group A; the optical
      densities (OD) were 1.72 +/- 0.6 and 0.699 +/- 0.25 for group A, 0.09 +/- 0.040
      and 0.230 +/- 0.47 for group B, and 0.0435 +/- 0.003 and 0.119 +/- 0.26 for group
      C (comparing group A with groups B and C combined, P < 0.001). ANA titers rose in
      groups A and B by age, but they were significantly higher at 14 weeks in group A.
      The mean titers were 1/286, 1/90, and 1/16 for A, B, and C, respectively (P <
      0.001). The platelet counts were not significantly different among the three
      groups. The titer size was significantly smaller in group A, as evidenced by the
      numbers of viable fetuses among the mice that became pregnant in each group:
      0.75, 2.45, and 5.5 in groups A, B, and C, respectively. Seven pregnant mice in
      group A had complete resorption, seven pregnant mice in group B showed focal
      (partial) resorption areas, by only one mouse in group C had complete resorption
      of the embryos, as shown by histopathological studies, although the fecundity
      rate was similar in the three groups. CONCLUSION: Our data suggest a pathogenic
      role for beta 2 GPI-induced aPL in the development of experimental models of APS
      in PL/J mice.

PMID- 9138446
TI  - TGF beta 2 in rabbit blastocoelic fluid regulates CD4 membrane expression:
      possible role in the success of gestation.
AB  - PROBLEM: During pregnancy, major changes occur in the decidual cell population.
      One of these changes involves some phenotypical transformations of lymphocyte sub
      populations. Since these variations might be due to the presence of the embryo,
      the current study was designed to investigate the implication of blastocoelic
      fluid (BF) in these changes and to determine the mechanism by which this
      phenomenon occurs. METHOD: Lymphocytes isolated from human peripheral blood (PBL)
      were cultured for 72 h in RPMI-FCS 10% and with or without BF day 12 (BF d-12) or
      Concanavalin A (ConA). After 72 h, T cells were labelled with anti-CD4 antibodies
      and Quantum Simply Cellular microbeads were used as a standard to evaluate the
      antibody binding capacity (ABC). RESULTS: Treatment of human PBL with BF d-12
      decreases the percentage of CD4 and TCR positive cells, as compared to non
      stimulated cells, but has no significant effect on CD2, CD3, and CD8 positive
      cells. It was also demonstrated, for the first time, that transforming growth
      factor beta-2 (TGF beta 2) in BF day 12 diminishes the percentage of CD4 positive
      cells by downregulating CD4 membrane expression on leucocytes. CONCLUSION: These
      findings suggest that the embryo plays a role in its own protection. Furthermore,
      it is predicted that any tissue producing TGF beta 2, such as certain types of
      tumor, downregulates the immune response, thus allowing tumor growth.

PMID- 9138447
TI  - The role of trophoblast interferons in the maintenance of early pregnancy in
      ruminants.
AB  - PROBLEM: Are the effects of ruminant trophoblast interferon-tau (IFN-tau) on
      uterine prostaglandin (PG) secretion a specific action of this cytokine and what
      are the effects of IFN-tau on expression of uterine genes not generally
      associated with pregnancy maintenance? METHODS: The effects of IFN-tau and IFN
      alpha on bovine uterine explant and epithelial cell production of PGF2 alpha and
      PGE2 were determined in the presence and absence of oxytocin (OT). The effects of
      intrauterine administration of IFN-tau were determined on uterine expression of
      retinol-binding protein (RBP) and transforming growth factor-beta (TGF-beta)
      isoforms. RESULTS: IFN-tau attenuated uterine endometrial secretion of PGF2 alpha
      and PGE2 in vitro and diminish PG stimulation by OT. IFN-tau and IFN-alpha were
      observed to be equipotent. Intrauterine infusion of IFN-tau resulted in a
      significant decrease in steady-state RBP mRNA levels and expression of TGF-beta
      1, 2, and 3 mRNA levels were lowest in IFN-tau treated animals. CONCLUSION:
      Negative regulation of gene expression may be a general strategy in IFN activity.
      This may explain the similar activities of IFN-tau and IFN-alpha on a broad
      variety of cell types, including ruminant uterine endometrium.

PMID- 9138448
TI  - NIH funding opportunities: tempora mutantur et nos mutamur in illis! (times are
      changing and we are changing with them).

PMID- 9138449
TI  - Lymphocyte immunotherapy (LI) increases serum levels of progesterone induced
      blocking factor (PIBF).
AB  - PROBLEM: To determine if allogenic stimulation from leukocyte immunization (LI)
      can increase the production of an immunomodulatory protein called progesterone
      induced blocking factor (PIBF) by CD8+ T-lymphocytes. METHODS: The study group
      consisted of 35 women, 29 who failed to conceive after repeated embryo transfers
      (ETs) and six with recurrent spontaneous abortion (RSA). The women underwent LI
      using the the male partner's blood as the source of leukocytes. Progesterone
      induced blocking factor was measured pre- and post-LI with an immunocytochemistry
      method using a PIBF-specific polyclonal antibody. RESULTS: The mean percentage of
      lymphocytes expressing PIBF, as well as the percentage of cases of whose PIBF
      level increased to 1% or more, was significantly higher post-LI, Similarly post
      LI, there was a significantly lower percentage of zero PIBF levels. CONCLUSIONS:
      Leukocyte immunization causes an increase in PIBF in many cases. Possibly the
      improved pregnancy outcome in immunized patients with RSA or previous failure to
      conceive with in vitro fertilization may be partially or possibly completely
      explained by its stimulatory effect on PIBF.

PMID- 9138450
TI  - Angiogenesis and the expression of vascular endothelial growth factor in
      endometrium and placenta.
AB  - PROBLEM: The demand for increased angiogenesis and microvascular permeability
      during cyclical changes in the endometrium and during placentation raises the
      possibility that aberrations in these events could lead to suboptimal
      reproductive performance. However, relatively little is presently known regarding
      the regulation of vascular growth and permeability in these tissues. METHOD OF
      STUDY: This review of current literature focuses on the expression, regulation,
      and potential physiological effects of vascular endothelial growth factor (VEGF)
      within endometrial and placental tissue. RESULTS: Spatial and temporal expression
      of VEGF as well as its restricted specificity, essential role in
      vasculogenesis/angiogenesis, and ability to induce vascular permeability makes
      VEGF an attractive regulator of vascular growth and permeability in the
      endometrium and placenta. CONCLUSION: A better understanding of the production,
      regulation, and physiological responses of the vasculature to angiogenic growth
      factors may lead to new therapeutic strategies for reproductive disturbances
      secondary to vascular insufficiencies within the female reproductive tract.

PMID- 9138451
TI  - Mucosal immunity in the human female reproductive tract: cytotoxic T lymphocyte
      function in the cervix and vagina of premenopausal and postmenopausal women.
AB  - PROBLEM: To investigate the mucosal immune system in the cervix and vagina of
      premenopausal women in terms of immune cells present and cytolytic capacity of
      mucosal CD3+ T cells in the lower reproductive tract. METHODS: Fresh tissue
      fragments prepared by vibratome sectioning were analyzed for the presence of
      cells by confocal scanning laser microscopy (CSLM). Isolated reproductive tract
      cells prepared by enzymatic were analyzed for CD3+ T cell phenotype by FACS
      analysis and for cytolytic function by an anti-CD3 mAb mediated redirected lysis
      assay. RESULTS: As determined by CSLM, CD3+ cells as well as macrophages and
      dendritic cells are distributed throughout the lower female reproductive tract in
      both the epithelium and subepithelial mucosa. It was found that cervical and
      vaginal tissues from pre- and post-menopausal women contain CD3+ T cells (CTL)
      that have cytolytic activity, when measured in an antigen non-specific anti-CD3
      mAb mediated redirected lysis assay. CONCLUSIONS: These results indicate that the
      lower reproductive tract of women is immuno-competent as judged by the presence
      of CD3, CD4, CD8, macrophage, and dendritic cells in the endocervix, ectocervix,
      and vagina of premenopausal and postmenopausal women. Further, these studies
      demonstrate that CD3+ T cells with cytolytic activity are present in the cervix
      and vagina during the proliferative and secretory phases of the menstrual cycle
      and following menopause.

PMID- 9138452
TI  - The implications of a paternally derived centrosome during human fertilization:
      consequences for reproduction and the treatment of male factor infertility.
AB  - PROBLEM: Successful fertilization in humans follows a complex series of events,
      including the completion of meiotic maturation of the oocyte with the extrusion
      of the second polar body, the decondensation of the sperm nucleus and the
      maternal chromosomes into male and female pronuclei, the restoration of the sperm
      centrosome, and the nucleation of microtubule-mediated motility necessary to
      bring the male and female pronuclei into close apposition. These events occur
      after both fertilization in vitro and after intracytoplasmic sperm injection
      (ICSI), a new technique which is currently being applied in many clinics to
      overcome severe male infertility. Defects in any of the events leading to
      fertilization can be lethal to the zygote and may prove to be causes of
      infertility. METHODS: Imaging of inseminated human and rhesus oocytes using
      immunohistochemical techniques reveals several phases at which fertilization
      arrests. RESULTS: Oocytes from some infertile patients failed to complete
      fertilization due to failure of the sperm aster microtubules in uniting the sperm
      and egg nuclei. The rate of sperm aster formation, size, and organization during
      fertilization has been used as a measurement of bovine sperm quality. The
      development of an assay using Xenopus laevis oocyte extract can also be used to
      test sperm from various species for their ability to form esters and perform
      other centrosomal functions in vitro, as well as another indicator of sperm
      quality. Semen from men with questionable fertility was found to contain sperm
      which are generally incapable of producing sperm asters. In addition, the
      activity of centrosomal proteins such as gamma-tubulin and centrin have been
      detected in mammalian eggs and sperm. The levels of gamma-tubulin increase
      markedly after exposure to X. laevis egg extract. CONCLUSION: Defects in either
      male or female nucleus decondensation also resulted in the arrest of
      fertilization and was found to occur in both inseminated human oocytes and in
      rhesus oocytes fertilized by ICSI. These discoveries on the molecular basis of
      infertility in humans have important implications for infertility diagnosis and
      managing reproduction.

PMID- 9138453
TI  - Review: cytokine involvement in ovarian processes.
AB  - PROBLEM: Expression of tumor necrosis factor-alpha (TNF) and interleukins 1 alpha
      and 1 beta (IL-1) have been reported in ovaries of several species and humans and
      are implicated in ovarian follicular development and atresia, ovulation,
      steroidogenesis, and corpus luteum function (including formation, development,
      and regression). The principal abnormal processes affected by these cytokines are
      ovarian cancer and reduction of ovarian function during sepsis. METHODS: A
      literature review. RESULTS: Numerous studies indicate that TNF and IL-1 inhibit
      gonadotropin-stimulated steroidogenesis of undifferentiated ovarian cells due to
      inhibition of adenylyl cyclase and post-cAMP sites. In differentiated ovarian
      cells, these cytokines either stimulate progesterone synthesis or have little to
      no effect on steroidogenesis. Both cytokines participate in ovulation and levels
      of these cytokines increase during the preovulatory period. Endotoxin inhibits
      gonadotropin-stimulated ovarian steroidogenesis and follicular development and
      these effects are mediated, in part, by TNF and by direct effects of endotoxin on
      ovarian cells. IN newly formed corpora lutea, progesterone secretion is inhibited
      by TNF and IL-1, although each has proliferative effects. TNF also has been
      implicated in regression of corpora lutea because TNF stimulates prostaglandin
      synthesis and luteal TNF increases after initiation of the decline in
      progesterone secretion. TNF and IL-1 are secreted by some ovarian cancer cells
      and stimulate growth of these cells. CONCLUSIONS: Thus, TNF and IL-1 are
      multifunctional factors affecting various ovarian processes.

PMID- 9138454
TI  - The interleukin-1 system and human implantation.
AB  - PROBLEM: Cytokines and growth factors are increasingly implicated in embryonic
      implantation. In the present study, we focus on the interleukin-1 system as an
      example of local regulator in human implantation. METHOD: Three different
      approaches are considered. First, we present evidence demonstrating its presence,
      regulation, and relevance on the human endometrium. Second, we demonstrate the
      presence of IL-1 system in the human embryo and the selective IL-1 release only
      when embryos were co-cultured with human endometrial epithelial cells (EEC) or
      EEC-conditioned media, indicating an obligate role of the endometrium in the
      regulation of the embryonic IL-1 system. Finally, we show data regarding the
      presence, hormonal regulation, and endometrial origin of IL-1 alpha, IL-beta, and
      IL-1ra levels in the endometrial fluid inside the endometrial cavity.
      Specifically, we present the IL-1 intracavitary microenvironment surrounding the
      human embryo at the apposition phase. RESULTS: This work suggests that the IL-1
      system seems to be relevant for human endometrial and embryonic physiology.
      Furthermore, this family of molecules must be considered as a relevant paracrine
      language displayed by both partners that may be important to endometrial and
      embryonic crosstalk during embryonic implantation.

PMID- 9138455
TI  - Genetic factors in reproduction and their evolutionary significance.
AB  - PROBLEM: The reproductive process is a major driving force in human evolution. An
      evolutionary perspective was brought to bear on some aspects of reproduction and
      its aberrations, and, conversely, some of the insights of modern reproductive
      genetics were used to investigate problems in evolution. METHOD: The data used
      were obtained from the literature in evolution, anthropology, archeology,
      linguistics, and genetics. RESULTS: The evolutionary line leading to modern
      humans diverged from that leading to the chimpanzees approximately 5-7 million
      years ago (Mya). Archaic Homo sapiens emerged ca. 0.3 Mya, and modern Homo
      sapiens and the development of language ca. 0.1 Mya; thus, modern humans occupy
      approximately 2% of the evolutionary history of the hominid line. During all of
      this time, the ancestors of modern humans were migratory hunter-gatherers. It was
      only during the Neolithic transition ca. 0.01 Mya (approximately 0.2% of hominid
      evolutionary history) that agriculture was developed, and with it a settled
      lifestyle that allowed a more stable existence and the development of a different
      reproductive pattern. Various estimates indicate that the human population
      increased from 0.05 million at the time of the emergence of modern Homo sapiens
      to 6,000 million at the present time (120,000-fold increase). CONCLUSIONS: These
      evolutionary considerations were used to explore three areas: (1) the extinction
      of the Neanderthals, who coexisted for ca. 65,000 years with modern humans; (2)
      the relatively low and stable rate of human conceptions (20-35% of ova fertilized
      naturally or fertilized in vitro); and (3) the long postnatal period required for
      the full maturation of the immune response. From these considerations, a broad
      view of the human reproductive process was obtained that may provide some insight
      into the rationale for the development of effective reproductive technologies.

PMID- 9138456
TI  - Human cytotrophoblastic cells absorb the NK blocking activity of monoclonal BA11.
AB  - PROBLEM: R80K is a polymorphic alloantigeneic protein present on human placental
      trophoblast and on paternal B lymphocytes and monocytes. This protein, unlike the
      former candidate TLX antigen, stimulates a protective maternal immune response in
      vivo. A murine monoclonal BA11 antibody, directed against R80K, prevents abortion
      in three murine pregnancy-failure models and inhibits human and murine NK
      activity. We attempted to define the target of BA11 in the human NK assay system.
      METHODS: A CELISA method was used to detect R80K antigen on the surface of
      different cells using the BA11 antibody. The effect, on human peripheral blood NK
      activity against K562, by BA11 before and after absorption by different cells,
      including the K562 target, was determined. RESULTS: R80K was detected on term
      placental syncytio and cytotrophoblast and on BeWo cells, by CELISA. BA11
      suppressed NK lysis of K562 cell sin a dose-dependent manner. Absorption of the
      BA11 by BeWo and by cytotrophoblastic cells significantly decreased the NK
      inhibitory activity. There was minimal absorption by K562 and BA11-pretreateed
      K562 cells remained susceptible to NK lysis. By contrast, BA11-pretreated
      peripheral blood cells lost all NK activity. CONCLUSIONS: The inhibition of NK
      killing of K562 cells by BA11 is more complex than simple masking of a
      trophoblast cell-associated molecule in K562 necessary for recognition in NK
      cells.

PMID- 9138457
TI  - Review: immunobiology of preeclampsia.
AB  - Preeclampsia has been recognized clinically since the time of Hippocrates:
      however its etiology and pathophysiology remain enigmatic. This pregnancy
      specific syndrome typically presents in late pregnancy as hypertension, edema,
      and proteinuria. Investigations over the past 15 years have revealed that
      preeclampsia is associated with abnormal placentation, reduced placental
      perfusion, endothelial cell dysfunction, and systemic vasospasm. Since it occurs
      more commonly in primigravidae and in women with underlying collagen-vascular
      diseases, an immunological component has long been suspected. Increased
      prevalence in high-order and molar pregnancies and those associated with
      increased placental mass suggests that trophoblastic volume and fetal antigen
      load are correlated with the syndrome. Epidemiological reports indicate that the
      prevalence of preeclampsia is decreased in women who received heterologous blood
      transfusions, practiced oral sex, or when a long period of cohabitation preceded
      an established pregnancy. Conversely, the use of condoms as a primary mode of
      contraception is associated with a higher risk of preeclampsia. These studies
      suggest that prior exposure to foreign or paternal antigens imparts a protection
      against the likelihood of developing preeclampsia. Clinical evidence of cellular
      and humoral immune dysfunction is associated with the syndrome. Fibrin and
      complement deposition and "foam" cells in atherosis lesions resemble the
      histopathology of renal allograft rejection. Relative T-cell, natural killer
      cell, and neutrophil activation have been reported in preeclampsia and
      circulating cytokines and antiphospholipid antibodies are more prevalent in
      preeclampsia than in normal pregnant women. These abnormalities are consistent
      with the systemic endothelial cell dysfunction that has been postulated as a
      pathophysiological feature of preeclampsia. While such associations do not prove
      causality, they suggest testable hypotheses for continued basic and clinical
      investigation of this major complication of human pregnancy.

PMID- 9138458
TI  - Regulation of abortion by gamma delta T cells.
AB  - PROBLEM: T cells are present at the feto-maternal interface, but their function
      during pregnancy has not been fully elucidated. T cells bearing gamma delta T
      cell receptor (TCR) may be particularly important, as some subsets can react to
      trophoblast cells by producing cytokines, such as interleukin-2 (IL-2). METHOD:
      We depleted T cells bearing the gamma delta receptor by injecting monoclonal
      antibodies (mAb) into females of the abortion-prone animal model CBA x DBA/2. We
      investigated the percentage and number of gamma delta T-cell receptor positive
      (TCR)+ cells in decidua and spleen during pregnancy in control and gamma delta
      depleted female mice. Pregnant females were also exposed to ultrasonic sound
      stress to boost the abortion rate. RESULTS: Stress failed to increase the
      abortion rate in the gamma delta TCR-depleted mice. FACScan analysis show that
      the ratio of cells bearing the gamma delta TCR dramatically decreased after
      injection of mAB to the gamma delta TCR in spleen and decidua, these cells
      recovered six days after depletion, showing a change in cytokine pattern. Levels
      of TNF-alpha in decidual gamma delta T cells decreased; similar effects of
      decreasing Th1 cytokines could be observed in splenic gamma delta T cells. We
      further identified increased levels of intracellular TNF-alpha in the V delta 4
      subset in the decidua, compared to spleen. CONCLUSIONS: Trophoblast recognition
      by the V delta 4 T-cell subset in the decidua may cause the release of
      abortogenic cytokines such as TNF-alpha. Depletion of such gamma delta TCR T
      cells during early pregnancy may promote successful pregnancy outcome in normal
      pregnancy and prevent stress-induced abortions.

PMID- 9138459
TI  - Stress triggered abortions are associated with alterations of granulated cells
      into the decidua.
AB  - PROBLEM: Stress is known to be abortogenic in animals and humans. An increased
      decidual release of cytokines such as TNF-alpha and reduction in TGF-beta 2
      related immunosuppressive activity has been proposed as the triggering mechanism.
      Substance P release by nerves in endometrium/decidua has been found to be the key
      neurotransmitter in this pathway. It is still unclear which cells are stimulated
      by substance P to produce the increased TNF-alpha level. METHOD: As a measure of
      local activation, the granulation of granulated material gland (GMG) cells was
      measured by flow cytometry after sonic plus immobilization stress of mice or
      substance P treatment of GMG cells (both isolated GMG cells and GMG-cell
      containing decidua). TNF-alpha release from decidua and isolated GMG cells was
      investigated using a TNF-alpha bioassay. The degranulation of uterine mast cell,
      another potential source of TNF-alpha, was examined in situ by Toluidine blue
      staining. RESULTS: We observed a striking increase in percentage of degranulated
      mast cells (8% -->24%) in the uteri of stressed animals, whereas the granularity
      of GMG cells was decreased by stress but increased with treatment with substance
      P in vitro. Isolated GMG cells appeared to release in vitro cytotoxins active in
      the TNF-alpha bioassay, but the magnitude of this activity was not increase by
      stress or by substance P treatment. In contrast, disaggregated decidual tissue
      which is known to release increased amounts of TNF-alpha after stress, did
      increase activity in response to substance P in vitro. CONCLUSIONS: Uterine mast
      cells show activation as reflected by degranulation after stress exposure of
      pregnant mice and mast cells might be the cellular link between the
      neurotransmitter substance P and increase in decidual TNF-alpha release that
      leads to abortion.

PMID- 9138460
TI  - Toxoplasmosis in HIV-positive women: seroprevalence and the role of prophylaxis
      in preventing disease.

PMID- 9138461
TI  - New thiazolo[3,2-a] pyrimidine derivatives, synthesis and calcium antagonistic
      activities.
AB  - The synthesis of a series of thiazolo[3,2-a]pyrimidine derivatives were
      described. The structures of the compounds were elucidated by IR, 1H-NMR, 13C and
      elementary analysis. The compounds were evaluated for their calcium antagonistic
      activities using nifedipine as standard compound. All of the compounds were found
      to be less potent than nifedipine.

PMID- 9138462
TI  - [The digital image archive--its clinical applications and importance in
      cardiology consulting by telemedicine].
AB  - The revolution in digital technology is rapidly changing the world of
      telecommunications. Its applications to Medicine, and in particular to
      Cardiology, offer enormous benefits since communication is an essential part of
      medical practice. The need to improve the management of medical information is
      critical because of the explosion of medical knowledge, and the need to provide
      comprehensive documentation on patient care. The availability of a network offers
      many possibilities for clinical, research and teaching activities. Relevant, up
      to-date scientific information is instantly available for analysis and
      interaction. The authors review the issue of digital communications as well as
      its potential application to Telemedicine, and present their preliminary
      experience with digital analysis and storage of echocardiographic images.

PMID- 9138463
TI  - [Left ventricular aneurysm. The surgical results and follow-up].
AB  - From May 1988 through October 1994, 44 patients with ischemic left ventricular
      aneurysm were operated upon. The mean age was 60.5 +/- 7.7 years and 36 patients
      (81.8%) were male. Thirty-two patients (72.7%) had congestive heart failure in
      NYHA class II or greater and 26 (59.1%) had moderate or severe left ventricular
      dysfunction. In 41 cases (93.2%) there was a history or electrocardiographic
      signs of myocardial infarction and only 3 patients (6.8%) were angina free. The
      location of the aneurysms was antero-apical or antero-lateral in 37 patients
      (84.1%) and inferior in 7 (15.9%), and intracavitary clot was present in 9 cases
      (20.5%). Fifteen patients (34.1%) were operated upon using standard linear
      repair, 8 (18.2%) by Stoney's technique and in the remaining 21 (47.7%) an
      endoventricular patch plasty was performed. All patients but one had CABG with a
      mean of 2.7 grafts per patient. The IMA was used in all patients with graftable
      LA disease (90.0%). Double IMA grafting was used in 10 patients (22.7%). Three
      patients (6.8%) had associated valvular surgery. Hospital mortality was 2.3% (1
      patient) and morbidity 22.7% (10 patients); intra-aortic balloon counterpulsation
      was required in two patients. The mean time of hospitalization was 13.5 +/- 9.0
      days. In the follow-up period (mean 29.2 +/- 21.5 months), 6 patients had
      required hospitalization (left ventricular failure -4; supraventricular
      arrhythmia-2) and two died. The remaining 32 survivors (78.0%) are in functional
      class I of the NYHA, without angina. Surgery of left ventricular ischaemic
      aneurysm was possible with low mortality and morbidity, with good functional
      results.

PMID- 9138464
TI  - [Incessant atrial tachycardia and peripartum cardiomyopathy--a therapeutic
      challenge].
AB  - Peripartum cardiomyopathy is an uncommon cause of heart failure but with serious
      prognosis. We report the case of a patient with peripartum cardiomyopathy
      presenting acute heart failure (severe biventricular systolic failure) and
      incessant atrial tachycardia, a rare arrhythmia difficult to control, that was
      responsible for cardiogenic shock, fetus death and multiple organ failure: renal
      failure (hemodialysis during 17 days), respiratory and hepatic failure and
      ischemic acute cholecystitis (treated surgically). After emergency cesarean
      section, heart rate control was obtained only after administering verapamil.
      Progressive clinical improvement with total recovery of hepatic and renal
      functions followed under treatment with vigorous multiple organ support. Six
      months after referral, the patients is doing well with normal daily life
      controlled with conventional therapy for heart failure, in stable sinus rhythm.
      Echocardiography shows a dilated left ventricle with partial resolution of
      systolic dysfunction rhythm. Echocardiography shows a dilated left ventricle with
      partial resolution of systolic dysfunction. The use of verapamil in severe
      biventricular systolic failure is discussed.

PMID- 9138465
TI  - [Direct angioplasty and thrombolysis in acute myocardial infarct].

PMID- 9138466
TI  - [The long-term angiographic follow-up of intracoronary stent implantation].

PMID- 9138467
TI  - [The implantation of Palmaz-Schatz stents via 6F catheters without oral
      hypocoagulation].

PMID- 9138468
TI  - [Direct coronary angioplasty: the time and therapeutic window].

PMID- 9138469
TI  - [Coronary angioplasty at a center without heart surgery. The experience of the
      1st year].

PMID- 9138470
TI  - [The prognostic value of left ventricular dysfunction in patients undergoing
      percutaneous coronary angioplasty].

PMID- 9138471
TI  - [Collateral circulation can influence the asymptomatic ST segment depression in
      stress tests performed after percutaneous coronary angioplasty].

PMID- 9138472
TI  - [Will there be a place for incomplete myocardial revascularization in elective
      coronary angioplasty?].

PMID- 9138473
TI  - [Hemodynamic evaluation in patients with chronic respiratory failure].

PMID- 9138474
TI  - p53 gene mutation analysis in porokeratosis and porokeratosis-associated squamous
      cell carcinoma.
AB  - In this and previous studies, we have shown p53 overexpression
      immunohistochemically in 14 of 17 porokeratotic specimens obtained from 14
      lesions of nine cases, and in all six specimens of squamous cell carcinoma (SCC)
      arising on porokeratotic lesions of two cases. We screened mutations in exons 5
      to 10 of the p53 gene in all these specimens by polymerase chain reaction-single
      strand conformation polymorphism analysis. Mutations of the p53 gene were
      detected in two of the six SCCs but not in any of the 17 porokeratotic specimens.
      These two mutations were C to T transitions at codons 146 and 175 in exon 5,
      which were a nonsense mutation at a dipyrimidine site and a missense mutation at
      a CG site, respectively. To our knowledge, neither of these mutations has been
      identified in skin cancers before. Our observations indicate that mutations of
      the p53 gene are not the major molecular etiology for porokeratosis, but are
      related to its skin carcinogenesis, and that p53 overexpression in porokeratosis
      is not due to p53 gene mutations.

PMID- 9138475
TI  - Recruitment of cycling epidermal cells and expression of filaggrin, involucrin
      and tenascin in the margin of the active psoriatic plaque, in the uninvolved skin
      of psoriatic patients and in the normal healthy skin.
AB  - The peripheral changes in the uninvolved skin adjacent to the extending psoriatic
      lesions may represent early events. The sequence of these events remains
      controversial. In the present study we evaluated epidermal and dermal aspects of
      the margin of the progressive psoriatic plaque, the distant uninvolved skin and
      normal healthy skin, using immunohistochemistry with markers for keratinization,
      proliferation and connective tissue: filaggrin, involucrin, Ki-67 and tenascin.
      The results showed that: (i) processes in distant uninvolved skin were comparable
      with the observations in normal skin; (ii) in the margin zone of the spreading
      psoriatic lesion, following the increased appearance of tenascin, the transition
      into parakeratosis, abnormal expression of filaggrin, involucrin and recruitment
      of cycling epidermal cells, happened simultaneously. The simultaneous
      normalization of these epidermal processes might be a consequence of a signal
      which is simultaneously transduced to the basal and suprabasal cell layers of the
      epidermis. Based on the present results and earlier findings, we would like to
      propose a triple stage model for the development of the psoriatic lesion: Stage
      1, involvement of the stroma; stage II, inflammatory infiltrate formation and
      penetration into the upper layers of the epidermis, with suprabasal expression of
      keratin 16; stage III, recruitment of cycling epidermal cells and abnormal
      terminal differentiation. Further studies are required on the regulation of
      tenascin expression, focusing on factors derived from the stroma affecting both
      recruitment of cycling epidermal cells, involucrin and filaggrin expression. An
      intermediate step in the dermo-epithelial interrelation is the inflammatory
      infiltrate, penetrating into the most superficial zone of the epidermis, and the
      suprabasal expression of keratin 16.

PMID- 9138476
TI  - Characterization of an interleukin 1 receptor antagonist protein released from
      ultraviolet-irradiated epidermal sheet.
AB  - An interleukin 1 (IL-1) inhibitor was detected in the culture supernatant of
      mouse epidermal sheet which had been irradiated with middle-wavelength
      ultraviolet (UVB) either in vitro or in vivo. Properties of the IL-1 inhibitor
      were consistent with those of IL-1 receptor antagonist (IL-1ra), i.e.,
      approximate molecular size of 17 kDa by gel filtration, specific inhibition of IL
      1-induced thymocyte proliferation, inhibition of binding of IL-1 to IL-1 receptor
      on the T-cell surface, and reactivity to anti-mouse IL-1ra antibody shown by
      immunoblotting and enzyme-linked immunosorbent assay (ELISA). These results
      indicate that this IL-1 inhibitor, which appears to be identical with IL-1ra, was
      released from the epidermis upon UVB irradiation, and that the inhibitor may
      participate in the regulation of inflammation mediated by IL-1, as well as in the
      pathogenesis of ultraviolet (UV)-induced immunosuppression.

PMID- 9138477
TI  - Comparison of the melanogenesis in human black and light brown melanocytes.
AB  - We examined how and to what extent the constitution of melanin and the
      expression, as well as the activity, of melanosomal proteins influence the
      production of melanin pigment by human black and light brown melanocytes, Mel (b)
      cells and Mel (l) cells, respectively. Melanin pigment in Mel (b) and Mel (l)
      cells consisted of a mixture of eumelanin and pheomelanin, and Mel (b) cells
      contained a larger amount. The signal intensity ratio of eumelanin to pheomelanin
      was similar in both cell types, though the two cell types differed in appearance.
      Tyrosinase activity and the amount of tyrosinase-related protein (TRP-1) of Mel
      (b) cells were higher than those of Mel (l) cells. Dopachrome tautomerase (DCT)
      activity and the amount of 6H5MICA were reduced in Mel (b) cells in comparison
      with Mel (l) cells. No significant difference in DHICA-converting activity or
      catechol-O-methyltransferase activity was found between Mel (b) and Mel (l)
      cells. There was no correlation between DHICA-converting activity and amount of
      TRP-1. These results suggest that the difference in the pigmentation of the two
      human melanocyte cell lines, Mel (b) and Mel (l), is derived from differences in
      the activity and expression of tyrosinase, TRP-1 and DCT, which affect the
      content and constitution of melanin polymers.

PMID- 9138478
TI  - Increased generation of hydrogen peroxide possibly from mitochondrial respiratory
      chain after UVB irradiation of murine fibroblasts.
AB  - The purpose of this study is to detect the generation of active oxygens in UVB
      irradiated murine fibroblasts and to propose new mechanisms. Decreased survival
      of fibroblasts under UVB irradiation was partially recovered by addition of
      catalase, DMSO or deferoxamine, suggesting the contribution of several types of
      active oxygen species. Then we examined the formation of active oxygen species
      and found that fibroblasts under UVB irradiation generated superoxide anion
      radicals (.O2-), intracellular H2O2, and hydroxyl radicals as estimated by the
      ESR-spin trapping method. Addition of thenoyltrifluoroacetone, which is an
      inhibitor of the mitochondrial respiratory chain, decreased 29% of the
      intracellular H2O2 levels in UVB-irradiated cells, but allopurinol, which is an
      inhibitor of xanthine oxidase, had no effect on them. On the basis of these
      results, we propose a a possible mechanism for damage of murine fibroblasts
      exposed to UVB in terms of generation of active oxygen species. The mitochondrial
      respiratory chain reaction stimulated by UVB irradiation enhances the generation
      of .O2-, which is in turn dismutated to H2O2 and O2 by superoxide dismutase. H2O2
      is then converted to hydroxyl radicals, catalyzed by trace elements such as iron,
      as suggested by Fenton-like reaction. Thus, hydroxyl radicals with higher
      reaction rate-constants than those of other active oxygen species to biomolecules
      are indicated to be responsible for the cytotoxicity in cells under UV
      irradiation.

PMID- 9138479
TI  - Effects of prostaglandin E1 on cultured dermal fibroblasts from normal and
      hypertrophic scarred skin.
AB  - To investigate the role of prostaglandin (PG) E1 in preventing scar formation as
      well as that of the related cytokines, we culture fibroblasts from hypertrophic
      scar tissue (SDF) and normal dermis (NDF) collected from patients with scar
      contracture. We have compared the type I collagen synthesis, type I collagenase
      activity, and the production of interleukin (IL)-6, IL-8 and transforming growth
      factor (TGF)-beta(1) in two types of cultured fibroblasts before and after
      addition of PGE1. Our results demonstrated that levels of type I collagen and TGF
      beta(1) production were higher and that type I collagenase activity and IL-8
      production were significantly lower in the culture supernatants of SDF. There was
      no significance difference in IL-6 production between SDF and NDF culture
      supernatants. On the other hand, PGE1 significantly increased type I collagenase
      activity and IL-8 production in the SDF culture supernatants and it increased IL
      6 and TGF-beta(1) production in both types of fibroblasts. However, there was no
      effect on synthesis of type I collagen in either group. To further investigate
      the role of TGF-beta(1) in NDF and SDF, exogenous recombinant human (rh) TGF
      beta(1) was added. In NDF group, rhTGF-beta(1) induced a decrease in the type I
      collagenase/type I collagen ratio, while rhTGF-beta(1) had no effect on the same
      ratio in the SDF group. These results suggest that PGE1 may have a role in the
      prevention of hypertrophic scar by increasing the activity of type I collagenase.

PMID- 9138480
TI  - Time course of changes in antioxidant enzymes in human skin fibroblasts after UVA
      irradiation.
AB  - Examining damage (inactivation) of antioxidant enzymes in the cells and the
      pattern of recovery after a single UV exposure might be a useful method for
      analyzing the mechanisms of chronic UV irradiation, because chronic UV
      irradiation means repeated single exposures. We irradiated human skin fibroblasts
      with a single exposure to UVA (1, 6 or 12 J/cm2) and examined the time course of
      changes in antioxidant enzymes over several days. Only catalase activity was
      inactivated at the end of the irradiation (66% for 6 J/cm2, 53% for 12 J/cm2),
      recovering by day 5. Superoxide dismutase (SOD) activity decreased on day 3 (63%
      for 6 J/cm2, 72% for 12 J/cm2), and recovered on day 5, although it was not
      changed at the end of exposure. The activities of glutathione peroxidase (GSH-Px)
      and glutathione reductase (GR) were nearly unchanged by irradiation. If repeated
      UV exposures occur before the inactivated enzyme activities recover, cellular
      damage will be significant due to the lowered antioxidant defense system. We
      examined the rates of synthesis and degradation of catalase in response to UVA
      irradiation. Both synthesis and degradation rates were changed by irradiation.
      These data indicate that catalase activity was still low on day 2 due to the
      existence of inactivated catalase produced at the end of UV irradiation, and
      catalase activities recovered by day 5 due to a significant increase in the
      synthesis rate. To elucidate the role of bound NADPH in catalase in response to
      UV irradiation, we measured the NADPH released from catalase after UVA
      irradiation using bovine liver catalase. UVA irradiation caused a release of
      NADPH from catalase (25% for 12 J/cm2), but this was not directly related to the
      inactivation of catalase.

PMID- 9138481
TI  - Immunohistochemical detection of p21WAF1/CIP1 and p53 proteins in formalin-fixed
      paraffin-embedded tissue sections of squamous cell carcinoma of the skin.
AB  - Thirty-two cases of squamous cell carcinoma (SCC) of the skin were investigated
      as to the expression of p53 and p21 (WAF1/CIP1) using an immunohistochemical
      method. These cases were surgically resected or biopsied, tissue samples were
      then fixed in formalin and embedded in paraffin in the conventional way.
      Microwave heating was used for antigen retrieval. The primary monoclonal anti-p21
      antibody and the monoclonal antibody against p53 were employed. The labeled
      streptoavidin-biotin-peroxidase method was used for immunohistochemical staining.
      Of these, 30 cases showed overexpression of p53 staining, but normal epidermal
      cells were free of stain. p21 positive cells were detected faintly in the middle
      layer cells of normal epidermis. Of these, 30 cases showed overexpression of p21
      staining. The staining pattern of p53 and p21 showed intratumoral heterogeneity
      in SCC. In general, there was the inverse relationship between p21 and p53
      staining in tumors, namely p53 positive cells were p21 negative and vice versa.
      However, some of the tumor cells expressed both genes simultaneously. This study
      supports a hypothesis that p21 expression is regulated by p53, and that it is
      also regulated by an additional pathway(s) in SCC.

PMID- 9138483
TI  - Peter James Leopard: Down Surgical Prize.

PMID- 9138482
TI  - Evaluation of cross-reacting anti-human antibodies in the euthymic hairless
      guinea pig model (HGP) suggests that the HGP may be a model for the study of
      proliferative skin disease.
AB  - Animal models have an important role in cutaneous research. The guinea pig has
      proven to be a useful model in a wide spectrum of these cutaneous studies;
      however, its usefulness is often compromised by the need for depilation. A
      euthymic hairless guinea pig (HGP) model avoids the problems associated with
      depilation. Morphologically, as in human skin, these animals have a multi-cell
      layer epidermis. Proliferation kinetic studies, as well as documentation of the
      degree of immunologic cross-reactivity between available antibodies to human
      cutaneous antigens, could extend the usefulness of this animal model. We
      performed a battery of anti-human antibodies on formalin fixed tissue, to a
      variety of antigens present within the skin and on inflammatory cells. These
      included CD3, UCHL-1, OPD4, L-26, KP-1, Factor XIIIa, S-100 protein, cytokeratin
      (AE1, AE3 and CK1), CAM 5.2, vimentin, CD 34, Factor VIII, fibronectin, SM actin,
      collagen IV, laminin, Bcl-2, p53, Ki-67, and PCNA. Cross-reacting antibodies
      included: CD3, S-100 protein, cytokeratin (AE1, AE3 and CK1), vimentin, Factor
      VIII, SM actin, collagen IV, p53, Ki-67, and PCNA. Although this battery of
      antibodies is limited, the markedly increased staining of Ki-67 and PCNA within
      keratinocytes in the epidermis as compared to normal human skin reflects a high
      proliferative rate. In addition, positive staining for p53, Ki-67, and PCNA may
      be useful in studying effects on cell cycle kinetics and apoptosis.

PMID- 9138484
TI  - [The development of the pigment epithelium and its interrelation with uveal
      pigment cells].
AB  - Authors propose one study of retinal cells population in different stages of
      ontogenesis and one study of the pigmentogenesis process at the level of uveal
      tract and external retinal stratum. The study was achieved with embryonic and
      fetal technique of paraffin inclusion. Concomitantly with loading with pigment of
      the external retinal stratum and so pigmentary uveal tract is present. Dynamics
      of the retinol cells population varies with stages and chronological age, the
      number of pigmented uveal cells increasing proportionally but at different
      parameters with the pigmented retinal stratum one simultaneous with age under
      influence specially of humoral factors.

PMID- 9138485
TI  - [Changes in the ocular tension of dialysis patients].
AB  - The paper represents one study of intraocular pressure effected at number of
      twenty patients with chronic Renal insufficiency, treated by dialysis, comparing
      the values of the intraocular pressure before and after the dialysis, we have
      found that the intraocular pressure has increased at twenty four eyes (64%) of
      the cases, white at eleven eyes (27,5%) the pressure failed and at fives eyes
      (12.5%) it has been constant. The increase of the intraocular pressure has never
      determined the increase over the upper borderline of 21 mmHg. The variations of
      the intraocular pressure postdialysis may be explained by some modifications into
      the osmolarity field.

PMID- 9138486
TI  - [Macular changes in patients with insulin-dependent diabetes mellitus].
AB  - We have studied, ophthalmoscopically and angiographically the macular
      modifications arisen within diabetic retinopathy in 79 individuals with insulin
      dependent diabetes (IDD). The 79 patients presented an unbalanced diabetes,
      suffering from the disease for 5-8 years. The age of these patients ranged
      between 29 and 41. In all these cases we have noticed the predominance of the
      macular form of the diabetic retinopathy. Often the disease showed non-typical
      modifications. It is important to mention that in 213 of the cases we have found
      incipient lesions of diabetic retinopathy in the ocular fundus: the lesions were
      few in many cases.

PMID- 9138487
TI  - [Pseudotumoral tuberculous choroiditis].
AB  - It is presented a case of a secondary tumoral retinal detachment that clinical
      examination and all paraclinical investigation go for a choroidal malignant
      melanoma. The anatomopathological examination of the enucleated eyeball has
      surprisingly put in evidence some choroidal consumptive lesions.

PMID- 9138488
TI  - [Recurrent palpebral keratoacanthoma].
AB  - One female patient in seventy-four years old presents one hyperkeratotic
      neoformation which covers upper eyelid, external canthus, lower eyelid in
      external part and palpebral fissure of the right eye. The affection appeared
      fifteen years ago. The extirpation was made eight years ago, relapsed and
      established one corneal ulcer. Extirpation of tumoral formation first of deeper
      eyelid and than of lower eyelid with cutaneous free skin graft it practised.
      Anatomopathological exam confirms the diagnosis of keratoacanthoma with
      acanthosis, hyperkeratosis and dyskeratosis of pluristratified epithelium. The
      basal membrane, is preserved, but it is masked here and there by an discreet
      chronic inflammatory process. It insists over the differential diagnosis with
      spinocellular epithelioma, the patient remaining in observation.

PMID- 9138489
TI  - [Accidents in the ocular area in children. An epidemiologic study and the
      medicosocial implications].
AB  - The authors have studied 202 ocular accidents with children, with a special
      insistence on epidemiology and medico-social implications. The accidents entail
      three important factors: the person liable to have an ocular accident, the agent
      provocateur, and a favourable human-social context. These factors were deeply
      analysed through a lot of parameters in a correlative manner. The authors
      demonstrate that the representative accidents are not usually unforeseeable
      incidents but they are avoidable and they have a prophylaxis with large means
      that can be applied. There were also attacked medico-social implications of the
      ocular accidents with a special insistence on the potential of invalidating
      consequences.

PMID- 9138490
TI  - [Promotion via competition].

PMID- 9138491
TI  - [The advantages and limits of computerized static perimetry].
AB  - Since 1990 it has become possible to perform Computerized Static Perimetry (PSC)
      in Romania too. It is presented the experience of University Eye Clinic Cluj with
      LED-PERS, a medium-performance perimeter, in early diagnosis of glaucoma and
      maculopathies. The author discusses the advantages and the limits of this method,
      from the point of view of the reliability indices and the quantification of
      results. The comments are valid for the other types of computerized static
      perimeters too.

PMID- 9138492
TI  - [Chronic tuberculous iridocyclitis].
AB  - One patient is seventy-one years old, diagnosed four years ago with latero
      cervical ganglionic tuberculosis, presents approximately one year and half,
      progressive loss of the vision in both eyes, predominant in the left-eye; for
      several months periocular pains referred to the left hemicranial field are
      presented. Ocular exam: visual acuity was 1/100 in the right eye and perception
      movements of the hand in the left eye: intraocular pressure was 28 mmHg in the
      right eye and 8 mmHg in the left eye: perikeratic congestion, chemosis, pigmented
      precipitates on the posterior face of the corneo, iris in "umbrella", seclusion
      and occlusion of the pupillary at the left eye, posterior synechiae at the right
      eye were noted. The eye ground exam is not possible due the pupillary partial
      seclusion at the right eye and the pupillary seclusion-occlusion at the left eye.
      The general exam releaves several latero-cervical keloid scars and pronounced
      dysphonia. Laboratory exam: IDR of the tuberculin was high positive, chest
      radiography shows hilar bilateral calcifications, ORL exam shows a tumor at the
      foot of the epiglottis and anatomopathological exam shows low differentiated
      epidermoid carcinoma. Using the anamnestic dates, clinical and paraclinical
      exams, we established the diagnosis: chronic tuberculosis iridocyclitis with
      pupillary seclusion and occlusion at the both eyes; secondary glaucoma at the
      right eye: latero-cervical ganglionic tuberculosis: epidermoid laryngeal
      carcinoma.

PMID- 9138493
TI  - [Adenocarcinoma of the meibomian gland with invasion of the orbit].
AB  - Adenocarcinoma of the meibomian glands is a tumor with atypical glandular
      features, that appear initially as a chalazion formation and then invades the
      neighbouring tissues. The patient, a 63 years old woman, presents a chalazion at
      the level of the left lower eyelid, which, after developing for a year, stars
      bleeding and infiltrates the ground of the inferior sac and the orbit. The
      tumoral formation makes a common body with the eyeball and the cornea, which,
      lacking protection, becomes opaque. Removal of the ulcerous eyelids is performed,
      with partial exenteration of the orbit. Anatomopathological investigation show
      the diagnosis: adenocarcinoma of the meibomian glands. Adenocarcinoma of the
      meibomian glands is the most malignant palpebral tumor. The signs of malignity
      are: infiltrated and relapsing aspect of the chalazion in on aged person, with
      low sebaceous secretion in the presence of pigmentations and bleedings in the
      tumor.

PMID- 9138494
TI  - [Parinaud's conjunctivitis].
AB  - A case of a 31-years-old young with swollen left eyelid, abundant discharge and
      giant conjunctival follicles of all palpebral conjunctiva. The existence of the
      left unilateral preauricular and submaxillary adenopathy associated with anatomo
      pathological exam of the conjunctival follicles decides the diagnosis of Parinaud
      conjunctivitis.

PMID- 9138495
TI  - [Staphylococcal anatoxin, an alternative in the treatment of endogenous uveitis].
AB  - The paper presents one clinical study effected by fourty-four patients with
      endogenous uveitis which beneficiary of a general treatment with staphylococcal
      anatoxin. The conclusions of the study impose that one effective treatment is
      obtained at the young patients with anterior, acute uveitis with moderate
      inflammatory phenomenon and what present one effective answer of the lymphocyte T
      by interleukin 1. The application of the treatment suppose several exams
      reminiscent of the immunologic status especially of the cellular immunology.

PMID- 9138496
TI  - [Ophthalmodynamometry. Current aspects].
AB  - In the paper we have pointed out the importance of ocular pressure in diagnosis
      of vascular-cerebral diseases. We have insisted upon the difficulties of
      interpreting the values of ocular pressure. The correlations between the maximum,
      medium and minimum values of ocular pressure are presented. We have also carried
      out a systematization of the four possibilities of altering the arteries
      resistance in the carotid system and pointed out the pathological situations
      which can determine changes of the ocular pressure. Presenting the method
      limitations we have emphasized the importance of the method in clinical practice.

PMID- 9138497
TI  - [The incision in the surgery of cataract and postoperative astigmatism].
AB  - There are presented effects of the incision in cataract surgery on postoperative
      astigmatism. Big changes of astigmatism can be eliminated by applying several
      basic principles of cataract incisions. Despite the rapid changes in incision
      technology, these concepts can be applied to all cataract surgery, whether a
      large or small incision is used, to achieve increased stability and decreased
      astigmatism. There are also reviewed possibilities of controlling postoperative
      astigmatism by varying the location and size of the cataract incision.

PMID- 9138498
TI  - [Rupture of the posterior capsule and the implantation of an artificial lens].
AB  - OBJECTIVE: Study of the incidence and side effects of the posterior capsule
      ruptures in a clinical trial. MATERIAL AND METHODS: Retrospective study of cases
      with posterior capsule ruptures encountered in a series of 162 with elective
      extracapsular extraction and posterior chamber lens implantation. RESULTS:
      Intraoperative posterior capsule ruptures occurred in 16 cases (10.12%), 4 cases
      without vitreous loss and 12 cases with vitreous loss. 12 cases were managed by
      simple posterior chamber lens implantation of with scleral or iris suture; in 4
      cases we preferred anterior chamber implants with flexible haptic: average
      postoperative visual acuity was 0.74 in the group with intact posterior capsule
      and 0.45 in the group with posterior capsule ruptures; average postoperative
      visual acuity was 2 lines higher in the group with posterior capsule ruptures
      without vitreous loss as compared with the group with posterior capsule ruptures
      and vitreous loss; postoperative complications were more frequent in the group
      with posterior capsule ruptures; intraocular lens descentrations were more
      frequent and more serious in the group with posterior capsule ruptures.
      CONCLUSIONS: Posterior capsule ruptures negatively affects the late functional
      results due to higher rate of major complications and to difficulties in
      artificial lens implantation.

PMID- 9138499
TI  - [Postoperative pseudophakogenic fibrinoplastic uveitis in young people].
AB  - The paper proposes systematizing of some pathogenic, clinical and therapeutical
      aspects in young patients with pseudofibrinous uveitis. Were analysed thirty-six
      patients with age below thirty years old which underwent a surgical act for
      cataract using extracapsular extraction and pseudophakic implant by posterior
      chamber. There patients were hospitalized in Ophthalmological Clinic of
      University Bucharest Hospital between 1995-1996. The postoperative uveitis
      occurred by 75 per cent, with maximum frequency at children. Clinical simple
      forms were prevalent and these responded very well at the treat. Were presented
      the therapeutical drafts used depending on clinical aspect as well therapeutical
      recent methods (laser ND-YAG fibrinectomy, gama TPA).

PMID- 9138500
TI  - [Carbonic anhydrase inhibitors with topical action in the treatment of
      glaucomatous diseases. A preliminary note].
AB  - Seven patients with open angle glaucoma were treated using Dorsolamida twice
      daily together Betablocant treat. Five patients with secondary glaucoma were
      treated with Dorsolamida three time daily as well three patients with edematous
      postimplant keratopathy. Intraocular pressure decreased with an average of 3-4 mm
      Hg and at the patients with corneal edema that decreased.

PMID- 9138501
TI  - [The characteristics of crystalline lens metabolism].
AB  - The crystalline lens has a slow metabolism comparatively with others ocular
      structures: its energy is necessary to keep the transparency, ensure the
      nourishment for development and growth of the fibres. At the origin of the
      cataract are the old mitochondria that establish decreasing of available energy.
      This decreases the transport and necessary metabolism for the synthesis of
      proteins.

PMID- 9138502
TI  - Isolated maxillary bending in CL/FR strain mice: observation of craniofacial
      deformity and inheritance pattern.
AB  - OBJECTIVE: The CL/Fr mouse, known as a strain with spontaneous cleft lip and/or
      palate (CL/P), has been used as an animal model to investigate etiology in CL/P.
      METHOD: We examined a facial asymmetry mutant discovered in a CL/Fr mouse colony
      that was not associated with CL/P and was shown to be inheritable in subsequent
      generations. Facial asymmetry became apparent with postnatal growth, whereas it
      was not detectable at birth, and was termed "maxillary bending" (MB) based on the
      characteristic bending of the maxilla. RESULTS: As a result of selective
      breeding, an 'MB line', In which MB was observed in 21.68% (67/309) in addition
      to CL/P in 17.80% (55/309) of the offspring, was developed in the CL/Fr colony.
      In mating experiments between the MB line and C57BL/6J, all F1 progeny showed the
      normal phenotype. MB was observed in 0.72% (1/139) of the F2 generation, and the
      backcross generation showed segregation of MB in 6.25% (22/352) and CL/P in 1.42%
      (5/352). These instances suggested the occurrence of an additional mutation in
      the CL/Fr mouse genome controlled by an autosomal recessive gene with low
      penetrance. However, since the CL/Fr mouse primarily has a developmental
      deficiency in the maxilla, the possibility that CL/P and MB share common
      etiologic factors cannot be completely ruled out. CONCLUSION: The maxillary
      bending retains significance, as this mutant can serve as an animal model of
      abnormal facial growth. Elucidation of the etiologic relationship between MB and
      CL/P may provide clues to clarifying the deficiency in first branchial arch in
      the mouse.

PMID- 9138503
TI  - Major residual deformities in cleft patients: a new anthropometric approach.
AB  - OBJECTIVE: A new method based on anthropometric ratios and inclinations was
      evaluated to confirm or reject whether residual deformities in cleft patients'
      faces differ significantly from faces without previous clefts. DESIGN, SETTING,
      AND PATIENTS: From a retrospective, a selective review of our clinical files,
      seven measurements were made on 156 photographs of the faces of 52 patients aged
      19 to 25 years. There ratios and two inclination angles were recorded for each
      patient. RESULTS: The primary hypothesis could be confirmed: the anthropometric
      ratios and angles used to express major residual deformities in cleft lip and
      nose patients differ significantly from normal values. CONCLUSION: This new
      method allows for objective measurement and evaluation of both the stigmata and
      the outcome of their treatment.

PMID- 9138504
TI  - Comparison of the reliability of craniofacial anatomic landmarks based on
      cephalometric radiographs and three-dimensional CT scans.
AB  - OBJECTIVE: Conventional cephalometry is an inexpensive and well-established
      method for evaluating patients with dentofacial deformities. However, patients
      with major deformities, and in particular asymmetric cases are difficult to
      evaluate by conventional cephalometry. Both two- and three-dimensional computed
      tomography (CT) have been proposed to alleviate some of these difficulties. Only
      a few studies using metallic markers have indicated 3-D CT to be a useful
      diagnostic method, whereas no studies have evaluated the reliability of the
      anatomic cephalometric points used in 3-D CT. The aim of our study therefore was
      to compare the reliability of anatomic cephalometric points from conventional
      cephalograms and 3-D CT. METHODS: Nine human dry skulls were CT scanned. In
      addition standard lateral and frontal cephalograms were obtained. The CT scans
      were 3-D image reconstructed, and the cephalometric points were recorded as x, y,
      and z co-ordinates by two investigators. Computerized cephalometrics were
      performed-on the lateral and frontal cephalograms. Intra- and interindividual
      variations were calculated for each method and tested for statistical
      significance. RESULTS: Lateral cephalogram measures were more reliable than 3-D
      CT, with interobserver variations less than 1 mm for most points compared to
      about 2 mm for 3-D CT. Lateral cephalometrics also showed significantly less
      interobserver variation for six variables. This was, however, less obvious when 3
      D CT was compared to frontal cephalograms. Frontal cephalometrics showed
      significantly less interobserver variation for three of the investigated
      variables. CONCLUSIONS: For standard lateral and frontal cephalometric points,
      there is no evidence that 3-D CT is more reliable than the conventional
      cephalometric methods in normal skull, and the benefit of 3-D CT cephalometric is
      indicated to be in the severe asymmetric craniofacial syndrome patients, as
      conventional cephalometrics is known to be inferior in these cases.

PMID- 9138505
TI  - Dental development in Apert syndrome.
AB  - OBJECTIVE: Apert syndrome has been extensively studied and described. However, an
      area that has not been studied is the dental development of these individuals.
      The purpose of this study was to evaluate the development of the dentition and
      compare it with that of unaffected children. There appears to be clinical
      observations indicating delayed eruption of the permanent teeth in the Apert
      child. METHODS: This retrospective study examined all Apert syndrome patients
      from four craniofacial centers who had a panoramic radiograph taken before the
      age of 16 years. Thirty-six individuals, 19 boys and 17 girls ranging in age from
      4.1 to 15.8 (mean = 9.3) years were examined. The seven left mandibular permanent
      teeth, second molar to central incisor, were rated on an eight-stage scale (A-H)
      using methods described by Demirjian and Goldstein (1976). The stage of each
      tooth was converted to the corresponding numeric value, and then all seven values
      were added to obtain a dental maturity score, which corresponded to a dental age,
      based on the sample of 4500+ normal children of the Demirjian et al. study. The
      dental age and chronologic age were length of delay was also determined. RESULTS:
      Thirty-one of 36 individuals had a dental age lower than their chronologic age.
      Compared to the normal sample, the mean developmental dental delay was 0.96 years
      (p < .001). The range in delay was 0.5 years advanced to 2.9 years delayed. There
      was a positive correlation to increased age with greater delay in dental
      development (p < .05). CONCLUSION: Our study confirmed our clinical impressions:
      The results showed a mean developmental delay of 0.96 years, with a trend of
      increasing delay with increased age. This positive correlation found between
      increased age and increased delay parallels the general growth of Apert children,
      with a greater degree of delay as the child grows older.

PMID- 9138506
TI  - Residual clefts in the hard palate: correlation between cleft size and speech.
AB  - OBJECTIVE: This study was conducted to evaluate the relationship between size of
      residual clefts in the hard palate and speech. SUBJECTS: Fifteen 7-year-old
      children born with complete cleft lip and palate were investigated. METHODS: All
      of the children were treated according to a surgical regimen involving early soft
      palate repair and delayed hard palate closure. Measures were taken of the area,
      length, and maximal width of the residual cleft in the hard palate about a year
      before its closure and correlated with a perceptual judgment of several speech
      variables. RESULTS: Significant positive correlations were obtained between the
      size of the cleft and two variables: weak pressure consonants and hypernasality.
      Nasal escape was very common among the patients, and almost half the children had
      retracted palatal or velar articulation of dental stop consonants. Neither of
      these two variables correlated with the size of the residual cleft. CONCLUSION:
      Perceived oral pressure and, perhaps, resonance seem to be related to size of the
      opening of the residual cleft, whereas audible nasal escape and articulatory
      compensations are not, at least not the latter once established.

PMID- 9138507
TI  - Effect of septal perforations on measures of nasal resistance.
AB  - OBJECTIVE: The purpose of this investigation was to determine the effect of
      septal perforations on posterior and anterior rhinomanometric measures of nasal
      resistance in an analog model. DESIGN: The data were analyzed using a repeated
      measures ANOVA. Nasal resistance was the dependent variable, while type of
      rhinomanometry, septal perforation size, and position of resistance (proximal vs.
      distal) were nominal scale independent variables. PARTICIPANTS: The analog model
      used in this study was similar to that described by Warren and Devereux (1966),
      except that the nasal cavities of the model were modified to create septal
      perforations. OUTCOME MEASURES: The main dependent measure was nasal resistance.
      RESULTS: An Important finding of this investigation was that septal perforations
      resulted in large differences (> 3 cm H2O/L/sec) between posterior and anterior
      nasal resistance values in the bilateral proximal resistor condition.
      CONCLUSIONS: Anterior rhinomanometry may underestimate true nasal resistance when
      a septal perforation is present, because the septal perforation prevents accurate
      measurement of nasopharyngeal pressure. Posterior rhinomanometric measures should
      accurately reflect nasal resistance despite septal perforations, because the
      perforation does not invalidate the estimate of nasopharyngeal pressure.

PMID- 9138508
TI  - Airway management in children with craniofacial anomalies.
AB  - Craniofacial anomalies (CFA) predispose children to airway obstruction. A
      retrospective study was conducted to describe airway intervention required to
      manage patients with craniofacial syndromes and diseases involving the midface
      and mandible (i.e., Pierre Robin, Apert, Treacher Collins, Saethre-Chotzen,
      CHARGE, Nager, Stickler, Goldenhar, and Pfeiffer). The type of airway
      intervention, duration of intervention, and associated physical and medical
      conditions were evaluated. One hundred nine patients had charts available for
      review and met inclusion criteria. Sixty-five of these patients required airway
      management, most commonly in the first month of life, ranging from positioning to
      tracheotomy. Nineteen patients required a tracheotomy. Associated medical
      conditions and feeding difficulties were associated with airway obstruction. This
      study evaluates factors that predispose children with CFA to have airway problems
      that need treatment, as well as the types of airway management that are
      necessary.

PMID- 9138509
TI  - Congenital bony syngnathia: a proposed classification.
AB  - Congenital bony syngnathia is an extremely rare condition characterized by bony
      fusion of the jaws. Five new cases are described and the existent literature is
      reviewed. A classification system is proposed and treatment recommendations based
      on this classification are presented.

PMID- 9138510
TI  - Early maxillary orthopedics in a child with an oblique facial cleft.
AB  - OBJECTIVE: Oblique facial clefts are extremely rare. In view of their
      variability, surgical treatment cannot be standardized. To date, early maxillary
      orthopedics in the treatment of oblique facial clefts have not been reported. The
      case described here presents a newborn child with a Tessier 3 cleft. Because of
      the enormous width of the alveolar cleft, a narrowing of the segments was
      regarded as prerequisite for definitive lip closure. To bring the segments
      together, an actively working plate with a forward pull was designed. CONCLUSION:
      After a period of 4 weeks, proper alignment and proximity of the segments were
      achieved, so that definitive lip closure and plastic reconstruction of the
      remaining soft tissue defect could be easier performed.

PMID- 9138511
TI  - Freeman-Sheldon syndrome: case management from age 6 to 16 years.
AB  - OBJECTIVE: This is the first description of long-term follow-up of a case of
      Freeman-Sheldon syndrome. Microstomia was treated with a mouth expander for 2 to
      3 hours per day before active orthodontic treatment. Separate impressions were
      necessary in each quadrant of both upper and lower jaws because of limited mouth
      opening. CONCLUSION: Orthodontic treatment improved the patient's Class II
      malocclusion, which was accompanied by crowding and a deep bite.

PMID- 9138512
TI  - Velopharyngeal incompetence as the presenting symptom of malignant brainstem
      tumor.
AB  - OBJECTIVE: When a patient presents with velopharyngeal incompetence (VPI) without
      an obvious structural or neurologic cause, the clinician is faced with a
      diagnostic challenge. We present an 11-year-old male with a long history of VPI
      who had been referred to our institution for evaluation and treatment. RESULTS:
      Detailed clinical examination and work-up revealed a malignant brainstem tumor.
      The presenting symptoms of breathiness associated with VPI had been overlooked by
      several different clinicians in the past. The patient successfully underwent a
      sphincter pharyngoplasty. CONCLUSIONS: A careful neurologic examination with
      special attention to the cranial nerves is necessary to identify subtle
      neurologic deficits and avoid delay in diagnosis. Differential diagnosis of
      neurogenic VPI is discussed.

PMID- 9138513
TI  - Some methods of assessing postnatal craniofaciodental growth: a retrospective of
      personal research.
AB  - OBJECTIVE: The purposes of this review and summary are to evaluate several
      selected significant clinical and basic science methods utilized to assess growth
      of bone(s), and in particular craniofaciodental growth: appositional and
      resorptive (bone), endochondral (bones), and sutural (bones). This personal
      retrospective report includes in part anthropometry, impressions and casts, vital
      markers, histology, radiopaque implant markers with and without serial
      cephalometric radiographs, and autoradiography. Knowledge obtained from the use
      of these various methods on rats, ground squirrels, rabbits, pigs, dogs, monkeys,
      and humans has contributed to a deeper and more fundamental understanding of both
      the processes and roles that craniofaciodental biology plays in the advancement
      not only of basic biology but also of craniofacial surgery. Growth and
      development of the skeletal system has an important role in determining body
      form. The dynamics of growth of bones is a complicated process. A number of
      different methods have been described by which growth of bones can be evaluated
      on both a quantitative and qualitative basis. No single method, however, should
      be relied on, because although it may have certain definite advantages, it also
      has its limitations. The use of all available methods at both the basic and the
      clinical science levels will give a more complete and accurate understanding of
      the problems associated with the growth of bone(s). CONCLUSIONS: Many of us are
      concerned with the correction of malformations and deformations that can be a
      result of faulty growth of bones. Thus, further knowledge obtained in regard to
      the sites, direction, and amount of growth as well as pattern, rate, and
      mechanism will lead not only to a more accurate diagnosis of the bony defect but
      also to a better understanding of both prevention and treatment.

PMID- 9138514
TI  - Facial growth in primary bone grafted unilateral clefts.

PMID- 9138515
TI  - Effects of vitamin B6 on beta-aminoproprionitrile-induced palatal cleft formation
      in the rat.
AB  - OBJECTIVE: This study was conducted to evaluate the effects of beta
      aminoproprionitrile and vitamin B6 on palatal clefting. METHOD: In four groups of
      pregnant Sprague-Dawley rats, beta-aminoproprionitrile (BAPN; 600 mg/kg b.w.) was
      given by gavage on embryonal day 15, 7 hours to induce palatal clefts. Vitamin B6
      (10 mg/kg b.w., IM) was given twice on embryonal day 14, 7 hours and on day 15, 7
      hours. The possibility that the food's content of vitamin B6 affected the results
      was also tested. Palatal cleft formation was divided into four different grades,
      ranging from no cleft formation to total cleft formation. RESULTS/CONCLUSION: It
      was found that BAPN induces cleft palate in rat fetuses and that this defect can
      be prevented both in number and severity by administration of vitamin B6 before
      and simultaneously with BAPN.

PMID- 9138516
TI  - [Injuries of the spine: current concepts in radiologic diagnosis].
AB  - This review discusses the usefulness of plain radiography, computed tomography
      (CT), and magnetic resonance imaging (MRI) in the evaluation of spinal trauma.
      The indications for the different imaging modalities in dependence on the
      specific pattern of injury are explored. Plain radiography still remains the
      prime method in the diagnosis of acute spinal trauma but there are substantial
      deficits, especially in the evaluation of the occipitocervical and the
      cervicothoracic junction as well as in the evaluation of the integrity of the
      posterior vertebral body line. If injury in these regions is suspected CT should
      follow plain radiography immediately. In the case of spinal trauma with
      unexplained neurologic deficits MRI is the method of choice for the detection of
      spinal cord injury. Recommendations with regard to instability and the
      classification of specific injuries, including examples of typical findings are
      presented.

PMID- 9138517
TI  - [MR angiography of the pelvic-leg blood vessels: current status and
      perspectives].
AB  - Currently 2D time-of-flight (TOF) MR angiography (MRA) is most commonly used for
      the evaluation of the extremities. The major limitation of all MRA techniques is
      their susceptibility to signal loss from intra-voxel phase dispersion. This leads
      to an overestimated grading of the stenosis. Further difficulties are motion
      artifacts and the limited spatial resolution. Therefore, MRA alone cannot be used
      routinely as a preoperative diagnostic procedure in patients with peripheral
      arterial disease. The postoperative examination of patients with vascular
      bypasses, however, seems to be a practical application of this technique. It is
      also possible to use MRA to image the lower limbs after percutaneous
      interventional angioplasty. The application of 2D-ECG-triggered sequences or the
      current fast technique of contrast-enhanced 3D-TOF MRA might play a role in
      combination with surface coils for future examinations of peripheral arterial
      disease.

PMID- 9138518
TI  - [Spiral computerized tomography diagnosis of abdominal seat belt injuries in
      children].
AB  - Seat belt injury (s.b.i.) arises from not properly applied seat belt in case of
      car accidents. The importance of spiral CT for the diagnosis of s.b.i.,
      especially of hidden traumatic lesions, will be demonstrated. Our experience
      includes 9 children in the age of 4 to 13 years suffering from life-threatening
      s.b.i. After life-saving treatment we took a spiral CT (Somatom plus S): first
      spiral CT, 10 mm slice thickness, without contrast medium (c.m.) and second
      spiral CT, 5 mm slice thickness, start delay 35-45 s after a large volume of c.m.
      Of these, 8 of 9 children survived. Besides bruising signs head injuries, and
      knee joint lesions in 4 of 9 cases, a combination of ruptured duodenum, ruptured
      liver or spleen, and chance fractures of the spine was found which is typical for
      s.b.i. In the remaining 5 cases, two of the lesions were combined. Rupture of the
      small bowel was manifested mainly as the discrete finding of free air or
      inhomogeneous ascites with a high density (bowel contents mixed with blood). Not
      only the emergency doctor but also the radiologist should take into account the
      complexity of seat belt injuries. Spiral CT is the imaging method of choice in
      the case of polytraumatic children.

PMID- 9138519
TI  - [Computerized tomography of retroperitoneal liposarcoma].
AB  - Besides the malignant fibrous histiocytoma, liposarcoma is one of the most common
      soft-tissue sarcomas seen in adults. They are most often localized in the lower
      extremity, followed by sarcomas in the retroperitoneal space which differ from
      the former in clinical appearance, epidemiology, and prognosis. The prognosis is
      especially dependent on tumor histology which is mainly classified into four
      subtypes. The aim of the study was to investigate whether there are specific CT
      features for each histologic subgroup, by analyzing the examination of 20
      patients. The highest percentage in fat and the biggest tumors were seen with
      well-differentiated liposarcomas (n = 4), whereas myxoid ones (n = 6) showed the
      sharpest margins. Round-cell (n = 2) and pleomorphic (n = 5) and pleomorphic (n =
      5) types showed mainly soft-tissue attenuation and could not be differentiated,
      either from each other or from other soft-tissue tumors. A clear identification
      of the histologic subgroup does not seem to be possible.

PMID- 9138520
TI  - [Interventional techniques in breast diagnosis: ultrasound controlled puncture
      biopsy].
AB  - From May 1, 1992 to April 30, 1993, we performed 307 ultrasonic guided, high
      speed core cut biopsies. In 119 of the 307 women, we dispensed with further
      surgical and histological procedures when the tentative diagnosis from
      complementary mammary diagnostic procedures revealed no pathological findings and
      concurred with the histological results of the core cut biopsy. In 188 women, the
      biopsy was followed by surgical intervention and correlation of the histological
      findings. This group of patients showed a sensitivity of 98%, a specificity and
      positive predictive value of 100%, and a negative predictive value of 91%. If we
      combine the results of the complementary mammary diagnostics (including the core
      cut biopsy), then the sensitivity, specificity, and positive and negative
      predictive values for this surgically and histologically confirmed group of
      patients reach 100%. In trained hands, the ultra-sonic-guided, high-speed core
      cut biopsy is a reliable means for determining the histological nature of lesions
      detected in ultrasonic scans. This technique has been perfected in our facility.
      Along with preoperative carcinoma detection, it permits us to avoid unnecessary
      operations when, under defined conditions, there are no pathological findings.

PMID- 9138521
TI  - [Value of the esophagogram in preoperative assessment of esophageal carcinoma].
AB  - PURPOSE: In this study we utilized barium swallows exhaustively in each patient.
      After that we compare the results with the intraoperative findings. The goal is
      to select those criteria which contribute to the preoperative clinical staging of
      esophageal carcinoma. METHODS: In a retrospective study we examined the
      esophagograms of 65 tumor patients. We evaluated the location and length of the
      tumor, the deformation of the esophageal axis, stenosis, dilatation, and the
      radiological type of the tumor. All characteristics were correlated with the
      pathologically determined TNM-criteria, the stage of the tumor, and the
      palliative or curative type of resection. RESULTS: We found the following
      significant correlations: localisation/T-criterion, radiological type/T-and M
      criteria, stenosis/type of resection, deformation of the axis, stenosis and
      radiological type/tumor stage. CONCLUSION: In the sense of a checklist the
      stenosis, the deformation of the esophageal axis and the radiological type of the
      tumor should be carefully evaluated and included in the report. With these data,
      the clinical stage of the tumor can be estimated.

PMID- 9138522
TI  - [MRI diagnosis and follow-up of bilateral necrosis of the humeral head as a
      complication after chemotherapy].
AB  - A 14-year old female patient was treated with chemotherapy including cortisone
      for malignant T-cell lymphoma. After chemotherapy she complained of pain in both
      hips and shoulders. Bone scintigraphy and conventional radiography failed to show
      any abnormality. However, bilateral femoral and humeral head necrosis was seen
      with MR imaging, which was also useful for follow up.

PMID- 9138523
TI  - [Nuclear magnetic resonance tomography examinations of the urogenital diaphragm
      in comparison with corresponding histomorphologic findings (the controversy
      concerning the musculus transversus perinei profundus)].
AB  - The transversus perinei profundus muscle is a well known structure in found
      anatomical textbook. Fibers of this muscle are believed to form the so-called
      external urethral sphincter (musculus sphincter urethrae). Recently
      histomorphologic investigations have shown that there is no muscular connection
      between the musculus sphincter urethrae (external sphincter) and the muscle
      system of the pelvic floor. Furthermore, the external sphincter was found to be
      divided into parts: the transversely striated part (musculus sphincter urethrae
      transversostriatus) and the smooth part (musculus sphincter urethrae glaber).
      Similar to histomorphologic investigations, contrast-enhanced MR imaging has
      shown the musculus sphincter urethrae to be surrounded by fatty and connective
      tissue only. Neither in MRI nor in anatomical slices can any connection between
      the urethral sphincter and the muscle system of the pelvic floor to be found.
      Thus, on the basis of the results presented in this work it is concluded that the
      musculus transversus perinei profundus does not exist in the form described in
      textbooks.

PMID- 9138524
TI  - ["Second opinion" in online radiology via Internet: report on implementation and
      analysis of reliability of findings in sectional images].
AB  - Numerous medical on-line services have already been established in the world-wide
      internet. In connection with the Information service TELESCAN, sponsored by the
      EU, a pilot project has been initiated which offers a radiological "second
      opinion" via the transmission of radiological findings and images that have been
      previously rendered anonymous. In addition to a description of the basic
      implementation, tests of the diagnostic certainty of the transmitted cranial
      computed tomographs have been performed. The CT images were digitized with a
      document camera, transmitted over the Internet, and then evaluated on the
      receiver's monitor. Both the transfer of originally generated digital image files
      (in ACR-NEMA or DICOM) as well as graphic files after digitization of X-ray
      films, for example by a document camera, is possible via electronic post (e
      mail). Visualization by the receiver requires the use of current proprietary
      software for special medical image formats, while standard graphic formats such
      as GIFF or JPEG can be visualized with the usual Internet software. In an ROC
      analysis, 56 individual images of cranial computed tomographs, half with
      pathological findings such as space-occupying lesions, infarcts, or brain edema,
      were tested with regard to the diagnostic certainty after digitization and
      transmission. In comparison with the original film findings, there was a slight
      but statistically not significant reduction in diagnostic certainty of the images
      evaluated on screen after transfer via the Internet. We believe that this result
      is due to the low local resolution, low dynamic range, the high image noise and
      of CT arising from the window technique. The same parameters are probably valid
      for MRI. The result cannot be applied to conventional radiography including
      mammography because, in comparison to the mentioned image techniques, their local
      resolution is high and image noise is considerably lower.

PMID- 9138525
TI  - [Digital radiography--results of a user survey (A) and consensus conference (B)].
AB  - Digital radiography is increasingly replacing conventional radiography in
      imaging. For some years now, the pros and cons of this new method have been
      subject to intense discussions. For further discussion, the present article
      describes the results of an inquiry among users and of a consensus conference
      held in March 1996 in Munich. Comments and interpretations have been omitted on
      purpose.

PMID- 9138526
TI  - Paul Ehrlich: pathfinder in cell biology. 1. Chronicle of his life and
      accomplishments in immunology, cancer research, and chemotherapy.
AB  - The paper reviews the life of Paul Ehrlich and his biomedical accomplishments in
      immunology, cancer research, and chemotherapy. Ehrlich achieved renown as an
      organic chemist, histologist, hematologist, immunologist, and pharmacologist. He
      disliked the formality of school but managed to excel in Latin and mathematics.
      His role model was an older cousin, Carl Weigert, who became a lifelong friend.
      Ehrlich studied medicine at Breslau, Strasbourg, Freiburg, and Leipzig, coming
      under the influence of Wilhelm Waldeyer, Julius Cohnheim, Rudolf Heidenhein, and
      Ferdinand Cohn. As a medical student, Ehrlich was captivated by structural
      organic chemistry and dyes. When he was 23, his first paper was published on
      selective staining. His doctoral thesis, "Contribution to the Theory and Practice
      of Histological Staining" contained most of the germinal ideas that would guide
      his future career. Most of his early work was centered in Berlin at Charite
      Hospital, where he did pioneering studies on blood and intravital staining, and
      at Robert Koch's Institute for Infectious Diseases, where he undertook important
      investigations in immunology. Ehrlich became an authority on antitoxin
      standardization and developed the "side-chain theory" of antibody formation for
      which he was later awarded the Nobel Prize. He became director of an Institute
      for Experimental Therapy in Frankfurt where he continued research in immunology
      and carried out routine serum testing. He developed new lines of investigation in
      cancer research and originated the field of chemotherapy. Using principles
      developed in his early work with dyes, he successfully treated certain
      experimental trypanosomal infections with azo dyes. His crowning accomplishment
      was discovering that the compound Salvarsan could control human syphilis.
      Ehrlich's legacy in immunology and chemotherapy is discussed and an intimate
      portrait is drawn of Ehrlich the person.

PMID- 9138527
TI  - Immunogold localization and quantification of cellular and subcellular abscisic
      acid, prior to and during drought stress.
AB  - An immunogold labeling procedure and experimental data are presented, which
      demonstrate that antibodies produced against a bovine serum albumin-abscisic acid
      conjugate can be used both to characterize the cellular and subcellular
      localization of abscisic acid (ABA), and to permit quantitative comparisons of
      this hormone in the subcellular compartments prior to and at times of drought
      stress. At the control leaf water potential (approximately -0.45 MPa), a
      quantitatively similar positive labeling pattern was observed in the chloroplasts
      and apoplast. A twofold drought stress-induced increase in the apoplastic ABA
      concentration was observed in the drought stressed leaf tissue (i.e., at a leaf
      water potential of approximately -1.55 MPa), while the ABA concentration in the
      chloroplasts did not differ from that of the controls. Three histochemical
      controls and the physiological observations validated the specificity of the
      procedure. Based on the labeling patterns we observed and literature cited, the
      validity of the hypothesis that drought stress induces a release of chloroplastic
      ABA is questioned. We interpreted our results as providing indirect evidence for
      a drought stress-induced root source origin for the increased apoplastic ABA
      concentrations.

PMID- 9138528
TI  - Detection of lamprin mRNA in the anadromous sea lamprey using in situ
      hybridization.
AB  - An optimal in situ hybridization protocol is described for the detection of gene
      expression of a structural protein unique to lampreys, lamprin, in the cartilages
      of prolarval, metamorphic and adult sea lamprey, Petromyzon marinus. A 156 bp
      antisense RNA probe labeled with (35)S-UTP was transcribed in vitro from a
      recombinant plasmid containing a cDNA insert homologous to the largest (1.8 kb)
      of three known mRNAs for the lamprin gene and hybridized to 6 mu m paraffin
      sections. Optimal signal to noise ratio was achieved by fixing tissues 30 min in
      4% paraformaldehyde and prehybridizing with a probe incorporating a
      nonradioactive S-UTP. Strong signals were visualized in all cartilaginous
      elements of the lamprey neurocranium; however, lamprin mRNA transcripts were not
      detected in branchial and pericardial cartilages suggesting differential
      expression of the lamprin gene. No signals were observed in tissue sections that
      had been treated with RNase A prior to hybridization or in sections hybridized
      with sense RNA probes. This technique has great potential for use in studies of
      the spatial and temporal distribution of cartilaginous components during
      developmental stages of lampreys.

PMID- 9138529
TI  - A double fluorescence staining protocol to determine the cross-sectional area of
      myofibers using image analysis.
AB  - A double fluorescence staining protocol was developed to facilitate computer
      based image analysis. Myofibers from experimentally treated (irradiated) and
      control growing turkey skeletal muscle were labeled with the anti-myosin antibody
      MF-20 and detected using fluorescein-5-isothiocyanate (FITC). Extracellular
      material was stained with concanavalin A (ConA)-Texas red. The cross-sectional
      area of the myofibers was determined by calculating the number of pixels (0.83 mu
      m(2)) overlying each myofiber after subtracting the ConA-Texas red image from the
      MF-20-FITC image for each region of interest. As expected, myofibers in the
      irradiated muscle were smaller (P < 0.05) than those in the non-irradiated
      muscle. This double fluorescence staining protocol combined with image analysis
      is accurate and less labor-intensive than classical procedures for determining
      the cross-sectional area of myofibers.

PMID- 9138530
TI  - The effect of decalcification and choice of fixative on histiocytic iron in bone
      marrow core biopsies.
AB  - IRon stains are often used for bone marrow core biopsies obtained by needle
      biopsy of the iliac crest. Because bone must be decalcified by brief treatment
      with acid, it is possible that an undetermined amount of stainable histiocytic
      iron may be lost. A study was carried out to determine whether decalcification
      results in loss of histiocytic iron and the effects of fixatives and the recovery
      of histiocytic iron in decalcified bone marrow tissue. Aspirates of bone marrow
      were stained for iron with Prussian blue. Because aspirate material does not
      require decalcification, it served as a control for the study. One hundred bone
      marrow biopsies and accompanying aspirates from 100 adult subjects were
      evaluated. Fifty bone marrow biopsies were fixed using a fixative containing
      mercuric chloride (B-5) and the remaining 50 were fixed in zinc-formalin.
      Histiocytic iron was graded as minimal, moderate or marked depending on whether
      less than 5, 6-10, or more than 10 iron positive histiocytes, respectively, were
      observed. When histiocytic iron was markedly present in aspirate material, at
      least moderate amounts of stainable iron were found in 22 of 25 B-5 fixed and 21
      of 25 zinc-formalin fixed decalcified bone marrow. When aspirate histiocytic iron
      was minimal or moderate, 14 of 25 B-5 fixed and 7 of 25 zinc-formalin fixed
      decalcified bone marrow specimens revealed histiocytic iron. Decalcification
      results in decreased recovery of stainable iron, and where histiocytic iron is
      minimally or moderately present, B-5 fixation results in greater
      postdecalcification recovery. There was no significant difference in recovery
      when larger quantities of histiocytic iron were present prior to the
      decalcification step.

PMID- 9138531
TI  - Gram staining applied to human spermatozoa: a simple method for studying
      chromatin condensation status.
AB  - Gram staining applied to human spermatozoa from fertile donors is described. The
      stain revealed populations of Gram-positive and Gram-negative spermatozoa. Data
      showed a significant and progressive decrease in the percentage of Gram-positive
      spermatozoa at different times during the chromatin decondensation procedure (SDS
      BSA and SDS-EDTA). No significant correlation could be found between Gram
      staining and other functional tests used for spermatozoa; only the aniline blue
      staining test showed a poor correlation. Our study demonstrates that normal
      spermatozoa with regular chromatin condensation appear Gram-positive, while
      spermatozoa with altered chromatin condensation appear Gram-negative.

PMID- 9138532
TI  - Static cytofluorometry and fluorescence morphology of mitochondria and DNA in
      proliferating fibroblasts.
AB  - The shape, distribution, and content of mitochondria in individual cells were
      examined during the cell cycle phases (G(0)/G(1), S, G(2) mitosis) in living
      human fibroblasts by static cytofluorometry and fluorescence microscopy. The
      morphocytochemical evaluations were performed in cell cultures submitted to
      double supravital fluorochrome staining with Hoechst 33342 and DiOC(6) to label
      DNA and mitochondria, respectively. The staining modalities were based on the
      stability of mitochondrial labeling. The G(1) to early S phases were
      characterized by the presence of filamentous mitochondria, except during the
      early postmitotic period. During late S, G(2), and mitotic phases, mitochondrial
      mass reached its highest value and mitochondria became short and numerous. During
      the last stage of mitosis, mitochondria were distributed among daughter cells
      through a cytoplasmic bridge.

PMID- 9138533
TI  - Differential staining for cellulosic and modified plant cell walls.
AB  - A simple method to enhance the staining of cell wall components for fluorescence
      microscopy is described. In stems of Nicotiana tabacum and needles of Pinus
      eldarica lignin, the cuticle and unsaturated lipids are indicated by a purple-red
      fluorescence while pectocellulosic components fluoresce pale blue.

PMID- 9138534
TI  - An immunocytochemical technique for analysis of regulation of genes encoding
      early differentiation marker antigens in an oocyte translation system.
AB  - Monoclonal antibodies are useful probes for analyzing cells at the molecular
      level at various developmental stages. Although identification of the genes
      encoding tissue- and stage-specific antigens could be informative for further
      molecular analysis, gene cloning is usually a time-consuming step, particularly
      when a monoclonal antibody is the only probe available. We describe here an
      immunocytochemical method for preliminary and immediate analysis of the
      regulation of antigen-coding genes. mRNAs purified from stage 27 and 38 Xenopus
      tadpoles were fractionated by size and injected into newt oocytes, from which
      frozen sections were prepared for immunostaining with tissue-specific monoclonal
      antibodies. Both of the antigens we tested, which are early markers for
      differentiating epidermal cells of Xenopus tadpoles, were detected in mRNA
      injected oocytes, but not in control oocytes. Immunostaining for each of the
      antigens showed that their relative levels in stage 27 and 38 tadpole tissue were
      reflected in those oocytes injected with mRNA purified from tadpoles of the
      respective stages. We suggest that this oocyte translation system combined with
      immunostaining provides for rapid analysis of changes in levels of antigen coding
      mRNAs throughout development.

PMID- 9138535
TI  - An automated double staining procedure for bone and cartilage.
AB  - Differential skeletal staining is an important part of developmental toxicologic
      studies. Traditionally these studies have required time-consuming differentiation
      of one or both stains used and careful attention to the maceration step to
      prevent specimen destruction. We present a fully automated protocol which does
      not require differentiation of either dye and incorporates a controlled
      maceration step which is highly reproducible. This has resulted in high quality
      staining that is reproducible, stable, and can be done in volume with minimal
      personnel time. The process involves the staining of skinned, eviscerated
      specimens fixed in 95% ethanol. Using an automated tissue processor, the specimen
      is stained in alcian blue for 24 hr, macerated in 3% potassium hydroxide for 24
      hr and stained with murexide for 24 hr. The specimens are cleared and preserved
      in glycerol. Within three days specimens have red stained bone and blue stained
      cartilage. The procedure was developed using 20-day-old Sprague-Dawley rat
      fetuses to evaluate the feasibility of using the procedure for teratology studies
      involving the fetal skeleton. Evenly stained specimens can be examined within
      three days and stored for years without loss of staining.

PMID- 9138536
TI  - Feulgen staining of intact plant tissues for confocal microscopy.
AB  - A method was developed to prepare plant structures for confocal laser scanning
      microscopy by combining Feulgen staining with pararosaniline and embedding in LR
      White(TM). This procedure preserves intact, delicate structures for three
      dimensional imaging without loss from sectioning or squashing, and the slides can
      be viewed several times without serious photo-bleaching.

PMID- 9138537
TI  - A new chelation method for determining ATPase activity in skeletal muscle.
AB  - Traditional methods for visualizing ATPase in sections use heavy metals that
      generate visible metal sulfide products. These methods use unpleasant and toxic
      reagents. We report a safer method using a novel ferric ion chelating agent to
      produce highly specific, low background, and permanent staining of muscle fiber
      enzymes.

PMID- 9138538
TI  - Plant cuticle staining with bismarck brown Y and azure B or toluidine blue O
      before paraffin extraction.
AB  - Transverse paraffin sections of mature greenwood stems of rose (Rosa x hybrida)
      and flowering dogwood (Cornus florida L.) were stained with Bismarck brown
      followed by azure B or toluidine blue 0. The Bismarck brown was replaced by
      thiazin dye metachromasia in all structures except the cuticle which remained
      brown or yellow. The interface between the cuticle and exterior cell walls of the
      epidermis was delineated clearly.

PMID- 9138539
TI  - Supravital uptake of methylene blue by dendritic cells within stratified squamous
      epithelia: a light and electron microscope study.
AB  - Electron microscopic data on methylene blue staining of dendritic cells in the
      epithelia of the soft palate and skin of the mouse after supravital dye injection
      are presented. The ultra-structural details were compared with corresponding
      light microscopic findings. Methylene blue stained tissue was fixed by immersion
      in a paraformaldehyde-glutaraldehyde solution containing phosphomolybdic acid.
      The ensuing dye precipitate was stabilized by ammonium heptamolybdate. The light
      microscopic investigation revealed that selective staining of dendritic cells
      depended on the presence of ambient oxygen. In addition, delicate morphological
      characteristics, like spinous structures of the dendrites, were visible. Some
      cells also showed terminal enlargements of the dendrites close to the surface of
      the epithelium. In general, visualization of morphological detail was superior to
      that obtained by conventional histological and immunohistochemical procedures.
      Nerve fibers were also stained within the epithelium as well as the subepithelial
      connective tissue. At the electron microscopic level, the dye was clearly
      identified as an electron dense precipitate that accumulated primarily within the
      cytoplasm near the plasma membrane. Furthermore, it was bound to the chromatin of
      the nuclei. No significant staining of mitochondria or other organelles was seen.
      Within the cytoplasm, the oxygen-dependent binding sites may be associated with
      heme proteins that attract both the dye in its reduced lipophilic leuco form and
      oxygen, followed by generation of oxygen radicals and a reoxidation of the leuco
      form to the cationic blue dye. Because of its selectivity for intraepithelial
      dendritic cells, the method described here supplements immunocytochemical
      procedures at both the light and electron microscopic levels.

PMID- 9138540
TI  - [High frequency jet ventilation during tracheal resection in children and
      infants].
AB  - Between 1986 and 1996, 16 infants and children less than 11 years of age (m = 11,
      f = 5) underwent resections for acquired or congenital tracheobronchial stenoses.
      During this period, various techniques of total intravenous anaesthesia (TIVA)
      were employed (midazolam, fentanyl, pancuronium; propofol, fentanyl,
      pancuronium). During the phase of dividing the airways, high-frequency-jet
      ventilation (HFJV) into the trachea or the main bronchi by 8-12Fr catheter(s) was
      applied for 10-75 min with driving pressures between 0.3-1.8 bar, frequencies
      between 100-200/min, I:E ratio between 1:4-1:1, and FjetO2 1.0. Catheter position
      was controlled visually, gas exchange was monitored by pulse oximetry and blood
      gas analysis. There were two incidents of transient hypoxaemia (paO2 less than 60
      mmHg), and 4 cases of hypercapnia (paCO2 more than 45 mmHg). No complications due
      to the HFJV-catheter technique, such as barotrauma or aspiration were seen. All
      children were kept postoperatively on a ventilator due to swelling of the airway
      anastomosis. In 5 children ventilator treatment exceeded 7 days, 3 children were
      discharged tracheostomised. These observations serve to confirm that HFJV is
      capable of maintaining gas exchange during tracheal resection in infants and
      children, if the following prerequisites are met: 1. Tracheobronchial pathology
      suitable for poststenotic placement of jet catheter. 2. No respiratory impairment
      by parenchymal pathology. 3. Monitoring by continuous visual control of
      respiratory mechanics, pulse oximetry and blood gas analysis. Cardiopulmonary
      bypass should be applied if airway pathology precludes safe placement of jet
      catheters, or in the presence of parenchymal respiratory failure.

PMID- 9138541
TI  - [EMLA for anesthesia of puncture sites for large lumen indwelling venous
      catheters for autologous plasma and erythrocyte concentrate donation].
AB  - OBJECTIVE: The analgetic effect of EMLA-Creme (Lidocaine-Prilocaine-Cream) was
      studied in 52 patients undergoing preoperative autologous blood and/or plasma
      donation. METHOD: 95 venous punctures were performed with a 18 G or 16 G cannula.
      Puncture pain was estimated by the patients using a visual analog painscore (VAS
      0-100). The data were evaluated regarding reaction time, puncture spot and
      cannula diameter. RESULTS: Within 15 minutes we find a clear reduction of
      puncture pain. The diameter of the cannula does not correlate with the painscore.
      Puncture of hand-back veins seems to be more painful than cubital vein puncture.
      CONCLUSION: The application of EMLA-Creme results in an effective analgesia for
      venous puncture. 37% of our patients were punctured without any pain and 67% felt
      a tolerable pain (VAS: 0-10).

PMID- 9138542
TI  - [Echocardiography values in the halothane uptake phase--measurement by acoustic
      quantification and manual evaluation].
AB  - In 35 ASA group I and II patients we investigated the influence of haemodynamic
      changes induced by increasing concentrations of halothane (from 0.0 to 0.6%
      halothane in 70% N20) on parameters of transesophageal echocardiography (TEE).
      Measurements by TEE were taken in manual and automatic boundary detection mode.
      In manual mode the left ventricular endsystolic area (ESA) increased
      significantly (+16.3%) and the fractional area change (FAC) decreased
      significantly (-14.9%). There was no significant change of left ventricular end
      diastolic area (EDA). In the automatic mode there was a significant increase of
      ESA and EDA (+13.8%; +6.0%) and a significant decrease of FAC (-10.9%). Peak
      ejection rate (PER) and peak filling rate (PFR) which were also assessed in
      automated mode decreased significantly (-10.0%; -5.7%) under halothane. No change
      occurred with manually determined left ventricular endsystolic wall stress
      (LVEWS). The endsystolic quotient decreased significantly both in manual and
      automated mode during halothane (-28.3%; -29.9%). No significant difference
      existed between TEE measurements under apnoea versus under controlled ventilation
      (except for EDA in automated mode). We conclude that there is no need for apnoea
      conditions for TEE measurements. In conclusion, TEE proves a useful monitoring
      system in anesthesia which enables the investigator to assess the negative
      inotropic effect of halothane. Problems in its practical usage are due to the
      wide variation of TEE measurements.

PMID- 9138543
TI  - [Comparative study of pethidine and clonidine for prevention of postoperative
      shivering. A prospective, randomized, placebo-controlled double-blind study].
AB  - OBJECTIVE: Patients with ischaemic heart disease and cardiac failure are
      endangered by an increase in oxygen consumption caused by postoperative
      shivering. The purpose of this study was to evaluate if pethidine and clonidine,
      which are well known for their effectiveness in the treatment of this undesirable
      side effect, can also prevent postoperative shivering if administered at the end
      of surgery. In addition it was investigated whether their intraoperative
      application influences the time of extubation and analgesics demand in the early
      postoperative period. METHODS: 60 patients (ASA I-II) scheduled for elective
      microsurgical vertebral disc resection were included in the study. After
      standardised induction of anaesthesia (5 mg x kg-1 thiopental, 2 micrograms x kg
      1 fentanyl, 0.1 mg x kg-1 vecuronium) lungs were ventilated with isoflurane
      vaporized in 66% N2O and 33% O2. The concentration of the inhalation anaesthetic
      was adjusted to maintain a surgical plane of anaesthesia without supplementary
      doses of opioids. Patients were randomly allocated in a double-blind fashion to
      one of three groups (each n = 20) to receive either pethidine (0.3 mg x kg-1) or
      clonidine (2 micrograms x kg-1) or 0.9% saline (control) 5 minutes prior to the
      end of surgery. Heart rate, arterial blood pressure and rectal temperature were
      measured at defined times, as well as the recovery time between the end of
      anaesthesia and extubation, incidence of postoperative shivering, and the pain
      level of the patients with a visual analog scale. The frequency and total demand
      of analgesics were determined using patient controlled analgesia and recorded for
      two hours postoperatively. RESULTS: The incidence of postoperative shivering in
      the clonidine group (5%) was less than in the pethidine group (25%) and
      significantly less than in the saline group (55%). Heart rate and blood pressure
      values after the administration of clonidine were lower than after pethidine and
      significantly lower than after saline. The time between end of surgery and
      extubation was similar in all groups with an average of 18 minutes. No
      significant differences among the pain scores and the analgesics demand were
      noted among any of the groups, including the saline control-group. CONCLUSION:
      Intraoperative administration of clonidine (2 micrograms x kg-1) is suitable for
      prevention of postoperative shivering. Despite its sedative effects the recovery
      time until extubation was not prolonged. 0.3 mg x kg-1 pethidine proved to be
      less beneficial.

PMID- 9138544
TI  - [Damage due to patient positioning in anesthesia and surgical medicine (1)].
AB  - Positioning a patient for surgery requires great care and caution. Correct
      positioning provides the surgeon with good access to the site, minimizes blood
      loss and reduces the risk of damage to nerves, soft tissue, compartments and the
      cardio-pulmonary system. Each position has its specific risks. These have to be
      evalued against the benefits. Extreme positions of the joints should be avoided
      whenever possible. The ulnar nerve or the plexus brachialis are at highest risk
      in the positioning of extremities. Good anatomical comprehension makes it
      possible to take effective counter-measures. In the case of damage to the ulnar
      nerve in spite of optimal positioning, some authors found pre-existent non
      symptomatic dysfunction in up to 30% of the cases. Patients suffering from
      peripheral vascular disease are usually at higher risk to suffer acute ischaemia,
      or, in the extreme, rhabdomyolysis with compartment syndrome, when positioned
      with elevated extremities (as in lithotomy position) or when a tourniquet is
      applied. Next to other factors, the duration of surgery seems to be of some
      importance. Operation sites above the heart carry a higher risk of venous air
      embolism unrelated to the positioning. In these cases adequate monitoring should
      be generously applied. Loss of visus is a rare but very severe complication most
      often seen in connection with the prone position. Still, postoperative blindness
      has occurred in all positions. It is absolutely imperative to avoid all pressure
      to the bulbus. The same law applies to surgery and positioning: indicated and
      correctly executed positioning, to which the patient has effectively consented,
      is legal, even if damage should occur. If the plaintiff demands compensation for
      damage, the distribution of onus of proof depends essentially on the accuracy of
      documentation. If documentation is faulty, the plaintiff may be granted relief or
      even shift of the onus of proof. This does not apply to a criminal lawsuit; in
      that case, culpable medical fallibility must be proven, since otherwise, the
      principle of "in dubio pro reo" applies. The interdisciplinary responsibilities
      concerning the positioning must be clearly defined and it is essential that the
      documentation of positioning as well as the documentation of positioning control
      is carried out as accurately as possible. Correct positioning can effectively aid
      surgery. Slovenly positioning should not be accepted, as there is a high
      probability of ill effects, possibly of permanent damage.

PMID- 9138545
TI  - [Xenon].

PMID- 9138546
TI  - [Environmental and work site contamination in anesthesia].

PMID- 9138547
TI  - [Reclaiming volatile and gaseous anesthetics].

PMID- 9138548
TI  - [Xenon as inhalation anesthetic].

PMID- 9138549
TI  - [Low flow anesthesia with xenon].

PMID- 9138550
TI  - [Acute respiratory insufficiency after inhaling concrete dust--a case report].
AB  - Inhalation of inorganic, inert dusts, like concrete dust, has generally not been
      considered dangerous. Very rarely alterations following chronic exposures can be
      observed, such as airflow obstruction and increased mucous secretion. Acute
      reactions in terms of acute respiratory failure have not been described so far.
      CASE REPORT: The present case report introduces a 54-year old male patient who
      developed acute respiratory failure after sawing a concrete block for several
      hours without wearing a face mask. Save for a chronic obstructive pulmonary
      disease he was unremarkable for his past medical history. When the emergency
      physician arrived, oxyhaemoglobin saturation was only 54%. Severely obstructed
      breathing sounds and coarse bubbling rales over both lungs were audible. After
      endotracheal intubation, a great deal of white viscous mucus could be aspirated
      via the tubus. The chest radiograph after admission demonstrated cloudy, shadowed
      areas with emphasis on both lower lung fields. As pulmonary function did not
      improve inspite of drug therapy with prednisolone, theophylline, fenoterol, n
      acetylcysteine and respiration therapy with 100% oxygen concentration, the
      patient was treated daily with bronchoscopic aspiration of the mucus. Only on the
      fourth day, after an additional ten hours in prone position, the lung function
      improved. The patient could be extubated on the fifth day. The final chest
      radiograph indicated no residuum apart from a very small shadowed area on the
      right angle between heart and diaphragm. CONCLUSION: The inhalation of dusts,
      which have long been considered inert, can cause acute pulmonary reactions. We
      suggest that the massive, mechanical covering on the alveolar layer with still
      alkaline concrete dust in conjunction with a history of chronic bronchitis was
      responsible for the acute inflammation and oedematous swelling of the bronchial
      mucosa, bronchospasm, secretion of a highly viscid mucus, atelectasis, and thus
      for the ARDS.

PMID- 9138551
TI  - [Acute theophylline intoxication as differential diagnosis of pneumothorax in an
      asthma patient].
AB  - The ambulance was called to a known asthmatic patient. On arrival, the team found
      a massively dyspnoeic, diaphoretic, non-cyanotic and somnolent patient. His
      medication consisted of oral theophylline (unknown dosage), fenoterol (metered
      dose inhaler), as well as 8 mg oral prednisolone. On the day of emergency, the
      patient had been treated by two physicians who applied two doses of i.v.
      theophylline and one dose of s.c. terbutaline because of bronchoconstriction
      (dosage not documented). The patient's pulse was frequent with 200 beats/min, the
      blood pressure not measurable. Careful i.v. titration of metoprolol was started
      to decrease the patient's heart rate and increase diastolic filling and stroke
      volume. However, the patient showed a progressive circulatory collapse. Following
      diagnostic thoracocentesis to rule out a left-side pneumothorax, the patient
      required intubation and mechanical ventilation because of increasing
      cardiovascular instability. A tension pneumothorax developed immediately after
      mechanical ventilation and required rapid treatment with a chest tube.
      Nevertheless, CPR and intravenous infusion of catecholamines were necessary
      before the patient was referred to a medical intensive care unit where he died
      the same day in cardiogenic shock. Clinical signs and symptoms associated with an
      elevated theophylline plasma level make theophylline toxicity the probable
      causative event for the patient's emergency condition of acute theophylline
      intoxication.

PMID- 9138552
TI  - Smooth muscle and skeletal muscle myosins produce similar unitary forces and
      displacements in the laser trap.
AB  - Purified smooth muscle myosin in the in vitro motility assay propels actin
      filaments at 1/10 the velocity, yet produces 3-4 times more force than skeletal
      muscle myosin. At the level of a single myosin molecule, these differences in
      force and actin filament velocity may be reflected in the size and duration of
      single motion and force-generating events, or in the kinetics of the cross-bridge
      cycle. Specifically, an increase in either unitary force or duty cycle may
      explain the enhanced force-generating capacity of smooth muscle myosin.
      Similarly, an increase in attached time or decrease in unitary displacement may
      explain the reduced actin filament velocity of smooth muscle myosin. To
      discriminate between these possibilities, we used a laser trap to measure unitary
      forces and displacements from single smooth and skeletal muscle myosin molecules.
      We analyzed our data using mean-variance analysis, which does not rely on scoring
      individual events by eye, and emphasizes periods in the data with constant
      properties. Both myosins demonstrated multiple but similar event populations with
      discrete peaks at approximately +11 and -11 nm in displacement, and 1.5 and 3.5
      pN in force. Mean attached times for smooth muscle myosin were longer than for
      skeletal-muscle myosin. These results explain much of the difference in actin
      filament velocity between these myosins, and suggest that an increased duty cycle
      is responsible for the enhanced force-generating capacity of smooth over skeletal
      muscle myosin.

PMID- 9138553
TI  - Probing protein hydration and conformational states in solution.
AB  - The addition of polyethylene glycol (PEG), of various molecular weights, to
      solutions bathing yeast hexokinase increases the affinity of the enzyme for its
      substrate glucose. The results can be interpreted on the basis that PEG acts
      directly on the protein or indirectly through water activity. The nature of the
      effects suggests to us that PEG's action is indirect. Interpretation of the
      results as an osmotic effect yields a decrease in the number of water molecules,
      delta Nw, associated with the glucose binding reaction. delta Nw is the
      difference in the number of PEG-inaccessible water molecules between the glucose
      bound and glucose-free conformations of hexokinase. At low PEG concentrations,
      delta Nw increases from 50 to 326 with increasing MW of the PEG from 300 to 1000,
      and then remains constant for MW-PEG up to 10,000. This suggests that up to MW
      1000, solutes of increasing size are excluded from ever larger aqueous
      compartments around the protein. Three hundred and twenty-six waters is larger
      than is estimated from modeling solvent volumes around the crystal structures of
      the two hexokinase conformations. For PEGs of MW > 1000, delta Nw falls from 326
      to about 25 waters with increasing PEG concentration, i.e., PEG alone appears to
      "dehydrate" the unbound conformation of hexokinase in solution. Remarkably, the
      osmotic work of this dehydration would be on the order of only one k T per
      hexokinase molecule. We conclude that under thermal fluctuations, hexokinase in
      solution has a conformational flexibility that explores a wide range of hydration
      states not seen in the crystal structure.

PMID- 9138554
TI  - Molecular dynamics simulations of six different fully hydrated monomeric
      conformers of Escherichia coli re-lipopolysaccharide in the presence and absence
      of Ca2+.
AB  - Six previously published conformational models of Escherichia coli Re
      lipopolysaccharide (ReLPS) were subjected to molecular dynamics simulations using
      the CHARMM force field. The monomers of ReLPS were completely immersed in a water
      box. The dynamic behavior of the solvated models in the presence and absence of
      calcium cations was compared. The structure of the solvent shell was analyzed in
      terms of radial distribution functions. Diffusion coefficients and mean residence
      times were analyzed to characterize the dynamic behavior of the solvent. Order
      parameters and number of gauche defects were used for the description of the
      dynamics of the acyl chains. The cations are preferentially located between the
      carboxylate and phosphate groups of the headgroup. Their presence leads to a
      rigidification of the headgroup structure and alters the conformation of the
      backbone, thus influencing the structure and flexibility of the hydrophobic
      region as well. The effect of calcium on the backbone flexibility was measured in
      terms of glycosidic torsion angles. The six fatty acid chains of each ReLPS
      monomer adopt a highly ordered micromembrane structure. The packing parameter
      indicates that aggregation of these ReLPS monomers will lead to lamellar
      structures. Evaluation of all data enables us to present one conformation, C,
      which is thought to best represent the average structure of the ReLPS conformers.

PMID- 9138555
TI  - The statistical-thermodynamic basis for computation of binding affinities: a
      critical review.
AB  - Although the statistical thermodynamics of noncovalent binding has been
      considered in a number of theoretical papers, few methods of computing binding
      affinities are derived explicitly from this underlying theory. This has
      contributed to uncertainty and controversy in certain areas. This article
      therefore reviews and extends the connections of some important computational
      methods with the underlying statistical thermodynamics. A derivation of the
      standard free energy of binding forms the basis of this review. This derivation
      should be useful in formulating novel computational methods for predicting
      binding affinities. It also permits several important points to be established.
      For example, it is found that the double-annihilation method of computing binding
      energy does not yield the standard free energy of binding, but can be modified to
      yield this quantity. The derivation also makes it possible to define clearly the
      changes in translational, rotational, configurational, and solvent entropy upon
      binding. It is argued that molecular mass has a negligible effect upon the
      standard free energy of binding for biomolecular systems, and that the cratic
      entropy defined by Gurney is not a useful concept. In addition, the use of
      continuum models of the solvent in binding calculations is reviewed, and a
      formalism is presented for incorporating a limited number of solvent molecules
      explicitly.

PMID- 9138556
TI  - The effect of intrinsic curvature on conformational properties of circular DNA.
AB  - Both thermal fluctuations and the intrinsic curvature of DNA contribute to
      conformations of the DNA axis. We looked for a way to estimate the relative
      contributions of these two components of the double-helix curvature for DNA with
      a typical sequence. We developed a model and Monte Carlo procedure to simulate
      the Boltzmann distribution of DNA conformations with a specific intrinsic
      curvature. Two steps were used to construct the equilibrium conformation of the
      model chain. We first specified the equilibrium DNA conformation at the base pair
      level of resolution, using a set of the equilibrium dinucleotide angles and DNA
      sequence. This conformation was then approximated by the conformation of the
      model chain consisting of a reduced number of longer, straight cylindrical
      segments. Each segment of the chain corresponded to a certain number of DNA base
      pairs. We simulated conformational properties of nicked circular DNA for
      different sets of equilibrium dinucleotide angles, different random DNA
      sequences, and lengths. Only random sequences of DNA generated with equal
      probability of appearance for all types of bases at any site of the sequence were
      used. The results showed that for a broad range of intrinsic curvature
      parameters, the radius of gyration of DNA circles should be nearly independent of
      DNA sequence for all DNA lengths studied. We found, however, a DNA properly that
      should strongly depend on DNA sequence if the double helix has essential
      intrinsic curvature. This property is the equilibrium distribution of the linking
      number for DNA circles that are 300-1000 bp in length. We found that a large
      fraction of the distributions corresponding to random DNA sequences should have
      two separate maxima. The physical nature of this unexpected effect is discussed.
      This finding opens new opportunities for joined experimental and theoretical
      studies of DNA intrinsic curvature.

PMID- 9138557
TI  - Sensing and refilling calcium stores in an excitable cell.
AB  - Inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ mobilization leads to depletion
      of the endoplasmic reticulum (ER) and an increase in Ca2+ entry. We show here for
      the gonadotroph, an excitable endocrine cell, that sensing of ER Ca2+ content can
      occur without the Ca2+ release-activated Ca2+ current (Icrac), but rather through
      the coupling of IP3-induced Ca2+ oscillations to plasma membrane voltage spikes
      that gate Ca2+ entry. Thus we demonstrate that capacitative Ca2+ entry is
      accomplished through Ca(2+)-controlled Ca2+ entry. We develop a comprehensive
      model, with parameter values constrained by available experimental data, to
      simulate the spatiotemporal behavior of agonist-induced Ca2+ signals in both the
      cytosol and ER lumen of gonadotrophs. The model combines two previously developed
      models, one for ER-mediated Ca2+ oscillations and another for plasma membrane
      potential-driven Ca2+ oscillations. Simulations show agreement with existing
      experimental records of store content, cytosolic Ca2+ concentration ([Ca2+]i),
      and electrical activity, and make a variety of new, experimentally testable
      predictions. In particular, computations with the model suggest that [Ca2+]i in
      the vicinity of the plasma membrane acts as a messenger for ER content via Ca(2+)
      activated K+ channels and Ca2+ pumps in the plasma membrane. We conclude that, in
      excitable cells that do not express Icrac, [Ca2+]i profiles provide a sensitive
      mechanism for regulating net calcium flux through the plasma membrane during both
      store depletion and refilling.

PMID- 9138558
TI  - Biophysical and functional consequences of receptor-mediated nerve fiber
      transformation.
AB  - Stimulation of the nervous system by substance P, a G protein-coupled receptor,
      and subsequent receptor internalization causes dendrites to change their shape
      from homogeneous cylinders to a heterogeneous string of swollen varicosities
      (beads) connected by thin segments. In this paper we have analyzed this
      phenomenon and propose quantitative mechanisms to explain this type of physical
      shape transformation. We developed a mathematical solution to describe the
      relationship between the initial radius of a cylindrical nerve fiber and the
      average radii of the subsequently created varicosities and connecting segments,
      as well as the periodicity of the varicosities along the nerve fiber. Theoretical
      predictions are in good agreement with our own and published experimental data
      from dorsal root ganglion neurons, spinal cord, and brain. Modeling the
      electrical properties of these beaded fibers has led to an understanding of the
      functional biophysical consequences of nerve fiber transformation. Several
      hypotheses for how this shape transformation can be used to process information
      within the nervous system have been put forth.

PMID- 9138560
TI  - Analytical description of the activation of multi-state receptors by continuous
      neurotransmitter signals at brain synapses.
AB  - Chemical synaptic transmission is a fundamental component of interneuronal
      communications in the central nervous system (CNS). Discharge of a presynaptic
      vesicle containing a few thousand molecules (a quantum) of neurotransmitter into
      the synaptic cleft generates a transmitter concentration signal that drives
      postsynaptic ion-channel receptors. These receptors exhibit multiple states, with
      state transition kinetics dependent on neurotransmitter concentration. Here, a
      novel and simple analytical approach for describing gating of multi-state
      receptors by signals with complex continuous time courses is used to describe the
      generation of glutamate-mediated quantal postsynaptic responses at brain
      synapses. The neurotransmitter signal, experienced by multi-state N-methyl-D
      aspartate (NMDA)- and L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate
      (AMPA)-type glutamate receptors at specific points in a synaptic cleft, is
      approximated by a series of step functions of different intensity and duration
      and used to drive a Markovian, multi-state kinetic scheme that describes receptor
      gating. Occupancy vectors at any point in time can be computed interatively from
      the occupancy vectors at the times of steps in transmitter concentration. Multi
      state kinetic schemes for both the low-affinity AMPA subtype of glutamate
      receptor and for the high-affinity NMDA subtype are considered, and expected NMDA
      and AMPA components of synaptic currents are calculated. The amplitude of quantal
      responses mediated by postsynaptic receptor clusters having specific spatial
      distributions relative to foci of quantal neurotransmitter release is then
      calculated and related to the displacement between the center of the postsynaptic
      receptor cluster and the focus of synaptic vesicle discharge. Using this approach
      we show that the spatial relation between the focus of release and the center of
      the postsynaptic receptor cluster affects synaptic efficacy. We also show how
      variation in this relation contributes to variation in synaptic current
      amplitudes.

PMID- 9138559
TI  - A novel method for structure-based prediction of ion channel conductance
      properties.
AB  - A rapid and easy-to-use method of predicting the conductance of an ion channel
      from its three-dimensional structure is presented. The method combines the pore
      dimensions of the channel as measured in the HOLE program with an Ohmic model of
      conductance. An empirically based correction factor is then applied. The method
      yielded good results for six experimental channel structures (none of which were
      included in the training set) with predictions accurate to within an average
      factor of 1.62 to the true values. The predictive r2 was equal to 0.90, which is
      indicative of a good predictive ability. The procedure is used to validate model
      structures of alamethicin and phospholamban. Two genuine predictions for the
      conductance of channels with known structure but without reported conductances
      are given. A modification of the procedure that calculates the expected results
      for the effect of the addition of nonelectrolyte polymers on conductance is set
      out. Results for a cholera toxin B-subunit crystal structure agree well with the
      measured values. The difficulty in interpreting such studies is discussed, with
      the conclusion that measurements on channels of known structure are required.

PMID- 9138561
TI  - Short-lived intermediates in aspartate aminotransferase systems.
AB  - The kinetics of the reaction of aspartate aminotransferase with erythro-beta
      hydroxy-aspartate, in which rapid mixing is followed (upon reaching a suitable
      stationary state) by a very fast temperature jump, is numerically simulated.
      Values for rate constants are used to the extent known, otherwise estimated. It
      is shown that reaction steps not resolvable by rapid mixing can be resolved by
      subsequent chemical relaxation. Since several absorption spectra of enzyme
      complexes overlap, use of a pH-indicator is investigated. When the pH-indicator
      is coupled to the protonic dissociation of free enzyme, the fast steps are easily
      detected in the chemical relaxation portion of the simulation. When the pH
      indicator is coupled to the protonic dissociation of the (short-lived) quinoid
      intermediate, protonic dissociation is easily detectable in the stopped flow
      phase and in the chemical relaxation phase. Such transient protonic dissociation
      has not been detected experimentally, but is predicted by the simulation. When
      natural substrates are used, the magnitude of the rate constants makes it
      unlikely that transient proton dissociation can be detected by stopped flow
      alone, but a combination of stopped flow with very fast temperature perturbation
      allows detection of the transient proton through use of a suitable nonbinding pH
      indicator. This is demonstrated by simulation for a specific case. Finally, an
      alternate mechanism is introduced and distinction of its kinetics from that of
      the original mechanism is demonstrated.

PMID- 9138562
TI  - Estimating the number of channels in patch-clamp recordings: application to
      kinetic analysis of multichannel data from voltage-operated channels.
AB  - Important kinetic information of voltage-operated ion channels can be obtained by
      estimating the open probability, the availability, and the first latency, and by
      applying run analysis. In the case of multichannel patches, estimation of the
      number of available channels is a prerequisite for the above analysis. Here we
      describe a method for calculation of the a posteriori probability of the number
      of available channels in each sweep by using the Bayes formula. This probability
      serves as a measure for the number of channels and allows for first latency
      determination and run analysis. The methods described were applied to simulated
      and experimental data obtained from L-type Ca2+ channel recordings.

PMID- 9138563
TI  - Conductivity noise in transmembrane ion channels due to ion concentration
      fluctuations via diffusion.
AB  - A Green's function approach is developed from first principles to evaluate the
      power spectral density of conductance fluctuations caused by ion concentration
      fluctuations via diffusion in an electrolyte system. This is applied to simple
      geometric models of transmembrane ion channels to obtain an estimate of the
      magnitude of ion concentration fluctuation noise in the channel current. Pure
      polypeptide alamethicin forms stable ion channels with multiple conductance
      states in artificial phospholipid bilayers isolated onto tips of micropipettes
      with gigaohm seals. In the single-channel current recorded by voltage-clamp
      techniques, excess noise was found after the background instrumental noise and
      the intrinsic Johnson and shot noises were removed. The noise que to ion
      concentration fluctuations via diffusion was isolated by the dependence of the
      excess current noise on buffer ion concentration. The magnitude of the
      concentration fluctuation noise derived from experimental data lies within limits
      estimated using our simple geometric channel models. Variation of the noise
      magnitude for alamethicin channels in various conductance states agrees with
      theoretical prediction.

PMID- 9138564
TI  - Single-channel properties of ionic channels gated by cyclic nucleotides.
AB  - This paper presents an extensive analysis of single-channel properties of cyclic
      nucleotide gated (CNG) channels, obtained by injecting into Xenopus laevis
      oocytes the mRNA encoding for the alpha and beta subunits from bovine rods. When
      the alpha and beta subunits of the CNG channel are coexpressed, at least three
      types of channels with different properties are observed. One type of channel has
      well-resolved, multiple conductive levels at negative voltages, but not at
      positive voltages. The other two types of channel are characterized by flickering
      openings, but are distinguished because they have a low and a high conductance.
      The alpha subunit of CNG channels has a well-defined conductance of about 28 pS,
      but multiple conductive levels are observed in mutant channels E363D and T364M.
      The conductance of these open states is modulated by protons and the membrane
      voltage, and has an activation energy around 44 kJ/mol. The relative probability
      of occupying any of these open states is independent of the cGMP concentration,
      but depends on extracellular protons. The open probability in the presence of
      saturating cGMP was 0.78, 0.47, 0.5, and 0.007 in the w.t. and mutants E363D,
      T364M, and E363G, and its dependence on temperature indicates that the
      thermodynamics of the transition between the closed and open state is also
      affected by mutations in the pore region. These results suggest that CNG channels
      have different conductive levels, leading to the existence of multiple open
      states in homomeric channels and to the flickering behavior in heteromeric
      channels, and that the pore is an essential part of the gating of CNG channels.

PMID- 9138565
TI  - Mechanosensitivity of an epithelial Na+ channel in planar lipid bilayers: release
      from Ca2+ block.
AB  - A family of novel epithelial Na+ channels (ENaCs) have recently been cloned from
      several different tissues. Three homologous subunits (alpha, beta, gamma-ENaCs)
      from the core conductive unit of Na(+)-selective, amiloride-sensitive channels
      that are found in epithelia. We here report the results of a study assessing the
      regulation of alpha,beta,gamma-rENaC by Ca2+ in planar lipid bilayers. Buffering
      of the bilayer bathing solutions to [Ca2+] < 1 nM increased single-channel open
      probability by fivefold. Further investigation of this phenomenon revealed that
      Ca2+ ions produced a voltage-dependent block, affecting open probability but not
      the unitary conductance of ENaC. Imposing a hydrostatic pressure gradient across
      bilayers containing alpha,beta,gamma-rENaC markedly reduced the sensitivity of
      these channels to inhibition by [Ca2+]. Conversely, in the nominal absence of
      Ca2+, the channels lost their sensitivity to mechanical stimulation. These
      results suggest that the previously observed mechanical activation of ENaCs
      reflects a release of the channels from block by Ca2+.

PMID- 9138566
TI  - Noise analysis of ion channels in non-space-clamped cables: estimates of channel
      parameters in olfactory cilia.
AB  - Ion channels in the cilia of olfactory neurons are part of the transduction
      machinery of olfaction. Odorant stimuli have been shown to induce a biphasic
      current response, consisting of a cAMP-activated current and a Ca(2+)-activated
      Cl- current. We have developed a noise analysis method to study ion channels in
      leaky cables, such as the olfactory cilium, under non-space-clamp conditions. We
      performed steady-state noise analysis on ligand-induced currents in excised
      cilia, voltage-clamped at input and internally perfused with cAMP or Ca2+. The
      cAMP-activated channels analyzed by this method gave results similar to those of
      single-channel recordings (gamma = 8.3 pS). Single-channel currents have not yet
      been recorded for the Ca(2+)-activated Cl- channels. Using our noise analysis
      method, we estimate a unit conductance, gamma = 0.8 pS, for these channels. The
      density of channels was found to be approximately 70 channels/micron2 for both
      channel species.

PMID- 9138567
TI  - Slow inactivation differs among mutant Na channels associated with myotonia and
      periodic paralysis.
AB  - Several heritable forms of myotonia and hyperkalemic periodic paralysis (HyperPP)
      are caused by missense mutations in the alpha subunit of the skeletal muscle Na
      channel (SkM1). These mutations impair fast inactivation or shift activation
      toward hyperpolarized potentials, inducing persistent Na currents that may cause
      muscle depolarization, myotonia, and onset of weakness. It has been proposed that
      the aberrant Na current and resulting weakness will be sustained only if Na
      channel slow inactivation is also impaired. We therefore measured slow
      inactivation for wild-type and five mutant Na channels constructed in the rat
      skeletal muscle isoform (rSkM1) and expressed in HEK cells. Two common HyperPP
      mutations (T698M in domain II-S5 and M1585V in IV-S6) had defective slow
      inactivation. This defect reduced use-dependent inhibition of Na currents
      elicited during 50-Hz stimulation. A rare HyperPP mutation (M1353V in IV-S1) and
      mutations within the domain III-IV linker that cause myotonia (G1299E) or
      myotonia plus weakness (T1306M) did not impair slow inactivation. We also
      observed that slow inactivation of wild-type rSkM1 was incomplete; therefore it
      is possible that stable membrane depolarization and subsequent muscle weakness
      may be caused solely by defects in fast inactivation or activation. Model
      simulations showed that abnormal slow inactivation, although not required for
      expression of a paralytic phenotype, may accentuate muscle membrane
      depolarization, paralysis, and sensitivity to hyperkalemia.

PMID- 9138568
TI  - Membrane potential and human erythrocyte shape.
AB  - Altered external pH transforms human erythrocytes from discocytes to stomatocytes
      (low pH) or echinocytes (high pH). The process is fast and reversible at room
      temperature, so it seems to involve shifts in weak inter- or intramolecular
      bonds. This shape change has been reported to depend on changes in membrane
      potential, but control experiments excluding roles for other simultaneously
      varying cell properties (cell pH, cell water, and cell chloride concentration)
      were not reported. The present study examined the effect of independent variation
      of membrane potential on red cell shape. Red cells were equilibrated in a set of
      solutions with graduated chloride concentrations, producing in them a wide range
      of membrane potentials at normal cell pH and cell water. By using assays that
      were rapid and accurate, cell pH, cell water, cell chloride, and membrane
      potential were measured in each sample. Cells remained discoid over the entire
      range of membrane potentials examined (-45 to +45 mV). It was concluded that
      membrane potential has no independent effect on red cell shape and does not
      mediate the membrane curvature changes known to occur in red cells equilibrated
      at altered pH.

PMID- 9138569
TI  - Cytoplasmic pH and human erythrocyte shape.
AB  - Altered external pH transforms human erythrocytes from discocytes to stomatocytes
      (low pH) or echinocytes (high pH). The mechanism of this transformation is
      unknown. The preceding companion study (Gedde and Huestis) demonstrated that
      these shape changes are not mediated by changes in membrane potential, as has
      been reported. The aim of this study was to identify the physiological properties
      that mediate this shape change. Red cells were placed in a wide range of
      physiological states by manipulation of buffer pH, chloride concentration, and
      osmolality. Morphology and four potential predictor properties (cell pH, membrane
      potential, cell water, and cell chloride concentration) were assayed. Analysis of
      the data set by stratification and nonlinear multivariate modeling showed that
      change in neither cell water nor cell chloride altered the morphology of normal
      pH cells. In contrast, change in cell pH caused shape change in normal-range
      membrane potential and cell water cells. The results show that change in
      cytoplasmic pH is both necessary and sufficient for the shape changes of human
      erythrocytes equilibrated in altered pH environments.

PMID- 9138570
TI  - Evidence for phospholipid microdomain formation in liquid crystalline liposomes
      reconstituted with Escherichia coli lactose permease.
AB  - The well-characterized integral membrane protein lactose (lac) permease from
      Escherichia coli was reconstituted together with trace amounts (molar fraction X
      = 0.005 of the total phospholipid) of different pyrene-labeled phospholipid
      analogs into 1-palmitoyl-2-oleoyl-sn-glycero-3-sn-glycero-3-phospho-rac'-glycerol
      (POPG) liposomes. Effects of lac permease on bilayer lipid dynamics were
      investigated by measuring the excimer-to-monomer fluorescence intensity ratio
      IE/IM. Compared to control vesicles, the presence of lac permease (at a
      protein:phospholipid stoichiometry P/L of 1:4.000) increased the rate of excimer
      formation by 1-palmitoyl-2[6-(pyren-1-yl)]decanoyl-sn-glycero-3-phosphocholine
      (PPDPC) by approximately fivefold. Decreasing P/L from approximately 1:4.000 to
      1:7.600 decreased the IE/IM for PPDPC from 0.16 to 0.05, respectively. An
      increase in bilayer fluidity due to permease is unlikely, thus implying that the
      augmented IE/IM should arise from partial lateral segregation of PPDPC in the
      vesicles. This notion is supported by the further 38% increase in IE/IM observed
      for the pyrene-labeled Cys-148 lac permease reconstituted into POPG vesicles at
      P/L 1:4000. The importance of the length of the lipid-protein boundary is
      implicated by the reduction in IE/IM resulting from the aggregation of the lac
      permease in vesicles by a monoclonal antibody. Interestingly, excimer formation
      by 1-palmitoyl-2[6-(pyren-1-yl)hexanoyl-sn-glycero-3-phosphocholine (PPHPC) was
      enhanced only fourfold in the presence of lac permease. Results obtained with the
      corresponding pyrenyl phosphatidylglycerols and -methanols were qualitatively
      similar to those above, thus indicating that lipid headgroup-protein interactions
      are not involved. Inclusion of 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamino-N
      (5-fluoresce inthio- carbamoyl) (DPPF, X = 0.005) into reconstituted lactose
      permease vesicles containing PPDPC caused a nearly 90% decrease in excimer
      fluorescence, whereas in control vesicles lacking the reconstituted protein only
      40% quenching was evident. The addition of 1,2-dipalmitoyl-sn-glycero-3-phospho
      rac'-glycerol (DPPG) decreased IE/IM for PPDPC, revealing the driving force for
      the lateral segregation of this probe to become attenuated. More specifically for
      protein-free bilayers at XDPPG = 0.10 the rate of lateral diffusion of PPDPC in
      POPG is diminished, as evidenced by the 24% decrement in IE/IM, under these
      conditions the increase in IE/IM due to lac permease was strongly reduced, by
      approximately 84%. The present data are interpreted in terms of the hydrophobic
      mismatch theory, which predicts that integral membrane proteins will draw lipids
      of similar hydrophobic thickness into their vicinity. In brief, the approximate
      lengths of most of the predicted 12 hydrophobic, membrane-spanning alpha-helical
      segments of lactose permease range between 28.5 and 37.5 A and thus exceed the
      hydrophobic thickness of POPG of approximately 25.8 A. Therefore, to reduce the
      free energy of the assembly, longer lipids such as PPDPC and DPPF are accumulated
      in the immediate vicinity of lactose permease in fluid, liquid crystalline POPG
      bilayers.

PMID- 9138571
TI  - Shape modification of phospholipid vesicles induced by high pressure: influence
      of bilayer compressibility.
AB  - Giant vesicles composed of pure egg yolk phosphatidylcholine (EYPC) or containing
      cholesterol (28 mol%) have been studied during a high hydrostatic pressure
      treatment to 285 MPa by microscopic observation. During pressure loading the
      vesicles remain spherical. A shape transition consisting of budding only occurs
      on the cholesterol-free vesicles during pressure release. The decrease in the
      volume delimited by the pure EYPC bilayer between 0.1 and 285 MPa was found to be
      16% of its initial volume, whereas the bulk compression of water in this pressure
      range is only 10%. So the compression at 285 MPa induced a water exit from the
      pure EYPC vesicle. The shape transition of the EYPC vesicle during pressure
      release is attributed to an increase in its area-to-volume ratio caused by the
      loss of its water content during compression. Because bulk compression of the
      cholesterol-containing vesicle is close to that of water, no water transfer would
      be induced across the bilayer and the vesicle remains spherical during the
      pressure release.

PMID- 9138572
TI  - Effect of hydrostatic pressure on water penetration and rotational dynamics in
      phospholipid-cholesterol bilayers.
AB  - The effect of high hydrostatic pressure on the lipid bilayer hydration, the mean
      order parameter, and rotational dynamics of 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine (DPPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)
      cholesterol vesicles has been studied by time-resolved fluorescence spectroscopy
      up to 1500 bar. Whereas the degree of hydration in the lipid headgroup and
      interfacial region was assessed from fluorescence lifetime data using the probe 1
      (4-trimethylammonium-phenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH), the
      corresponding information in the upper acyl chain region was estimated from its
      effect on the fluorescence lifetime of and 3-(diphenylhexatrienyl)propyl
      trimethylammonium (TMAP-DPH). The lifetime data indicate a greater level of
      interfacial hydration for DPPC bilayers than for POPC bilayers, but there is no
      marked difference in interchain hydration of the two bilayer systems. The
      addition of cholesterol at levels from 30 to 50 mol% to DPPC has a greater effect
      on the increase of hydrophobicity in the interfacial region of the bilayer than
      the application of hydrostatic pressure of several hundred to 1000 bar. Although
      the same trend is observed in the corresponding system, POPC/30 mol% cholesterol,
      the observed effects are markedly less pronounced. Whereas the rotational
      correlation times of the fluorophores decrease in passing the pressure-induced
      liquid-crystalline to gel phase transition of DPPC, the wobbling diffusion
      coefficient remains essentially unchanged. The wobbling diffusion constant of the
      two fluorophores changes markedly upon incorporation of 30 mol% cholesterol, and
      increases at higher pressures, also in the case of POPC/30 mol% cholesterol. The
      observed effects are discussed in terms of changes in the rotational
      characteristics of the fluorophores and the phase-state of the lipid mixture. The
      results demonstrate the ability of cholesterol to adjust the structural and
      dynamic properties of membranes composed of different phospholipid components,
      and to efficiently regulate the motional freedom and hydrophobicity of membranes,
      so that they can withstand even drastic changes in environmental conditions, such
      as high external hydrostatic pressure.

PMID- 9138573
TI  - Theoretical considerations on myofibril stiffness.
AB  - A discrete model of the interaction between individual myofilaments was developed
      to study the stiffness of a sarcomere for the case in which filament compliance
      is not negligible. Our model retains, in the limit, the characteristics of the
      previously published model by Ford et al. (Ford, L. E., A. F. Huxley, and R. M.
      Simmons. 1981. The relation between stiffness and filament overlap in stimulated
      frog muscle fibres. J. Physiol. 311:219-249). In addition, the model is able to
      model the interaction in cases in which few cross-bridges are attached, or when
      the distribution of attached cross-bridges is not uniform. Our results confirm
      previous indications that it might be impossible to calculate the number of
      attached cross-bridges by using only stiffness measurements in quick-stretch (or
      release) experiments.

PMID- 9138574
TI  - Inhibition of cross-bridge binding to actin by caldesmon fragments in skinned
      skeletal muscle fibers.
AB  - Several regions within the 35-kDa COOH-terminal portion of caldesmon have been
      implicated in the ability of caldesmon to inhibit actin-activated myosin ATPase
      activity. To further define the functional regions of caldesmon, we have studied
      the effects of three chymotryptic fragments, one fragment produced by CNBr
      digestion and two fragments produced by digestion with submaxillaris arginase C
      protease, on the relaxed stiffness and active force of rabbit psoas fibers. Each
      of the regions of caldesmon studied had either direct or indirect effects on
      single-fiber mechanics. The 35-kDa and 20-kDa fragments of caldesmon, like intact
      caldesmon, were effective inhibitors of fiber stiffness, a measure of cross
      bridge attachment. The 7.3-kDa and 10-kDa fragments, which constitute the NH2 and
      COOH halves of the 20-kDa fragment, inhibited both relaxed fiber stiffness and
      active force production, but with a reduced efficacy compared to the 20-kDa
      fragment. These results suggest that several regions within the 35-kDa COOH
      terminal region of caldesmon are required for optimum function of caldesmon and
      that function includes inhibition of weak cross-bridge attachment and force
      production.

PMID- 9138575
TI  - Calcium regulation of skeletal muscle thin filament motility in vitro.
AB  - Using an in vitro motility assay, we have investigated Ca2+ regulation of
      individual, regulated thin filaments reconstituted from rabbit fast skeletal
      actin, troponin, and tropomyosin. Rhodamine-phalloidin labeling was used to
      visualize the filaments by epifluorescence, and assays were conducted at 30
      degrees C and at ionic strengths near the physiological range. Regulated thin
      filaments exhibited well-regulated behavior when tropomyosin and troponin were
      added to the motility solutions because there was no directed motion in the
      absence of Ca2+. Unlike F-actin, the speed increased in a graded manner with
      increasing [Ca2+], whereas the number of regulated thin filaments moving was more
      steeply regulated. With increased ionic strength, Ca2+ sensitivity of both the
      number of filaments moving and their speed was shifted toward higher [Ca2+] and
      was steepest at the highest ionic strength studied (0.14 M gamma/2).
      Methylcellulose concentration (0.4% versus 0.7%) had no effect on the Ca2+
      dependence of speed or number of filaments moving. These conclusions hold for
      five different methods used to analyze the data, indicating that the conclusions
      are robust. The force-pCa relationship (pCa = -log10[Ca2+]) for rabbit psoas
      skinned fibers taken under similar conditions of temperature and solution
      composition (0.14 M gamma/2) paralleled the speed-pCa relationship for the
      regulated filaments in the in vitro motility assay. Comparison of motility
      results with the force-pCa relationship in fibers suggests that relatively few
      cross-bridges are needed to make filaments move, but many have to be cycling to
      make the regulated filament move at maximum speed.

PMID- 9138576
TI  - Cryo-atomic force microscopy of smooth muscle myosin.
AB  - The motor and regulatory domains of the head and the 14-nm pitch of the alpha
      helical coiled-coil of the tail of extended (6S) smooth-muscle myosin molecules
      were imaged with cryo atomic force microscopy at 80-85 K, and the effects of
      thiophosphorylation of the regulatory light chain were examined. The tail was 4
      nm shorter in thiophosphorylated than in nonphosphorylated myosin. The first
      major bend was invariant, at approximately 51 nm from the head-tail junction (H
      T), coincident with low probability in the paircoil score. The second major bend
      was 100 nm from the H-T junction in nonphosphorylated and closer to a skip
      residue than the bend (at 95 nm) in thiophosphorylated molecules. The shorter
      tail and distance between the two major bends induced by thiophosphorylation are
      interpreted to result from melting of the coiled-coil. An additional bend not
      previously reported occurred, with a lower frequency, approximately 24 nm from
      the H-T. The range of separation between the two heads was greater in
      thiophosphorylated molecules. Occasional high-resolution images showed slight
      unwinding of the coiled-coil of the base of the heads. We suggest that
      phosphorylation of MLC20 can affect the structure of extended, 6S myosin.

PMID- 9138577
TI  - Measurements of Ca2+ entry and sarcoplasmic reticulum Ca2+ content during the
      cardiac cycle in guinea pig and rat ventricular myocytes.
AB  - This study investigates the contribution of Ca2+ entry via sarcolemmal (SL) Ca2+
      channels to the Ca2+ transient and its relationship with sarcoplasmic reticulum
      (SR) Ca2+ content during steady-state contraction in guinea pig and rat
      ventricular myocytes. The action potential clamp technique was used to obtain
      physiologically relevant changes in membrane potential. A method is shown that
      allows calculation of Ca2+ entry through the SL Ca2+ channels by measuring Cd(2+)
      sensitive current during the whole cardiac cycle. SR Ca2+ content was calculated
      from caffeine-induced transient inward current. In guinea pig cardiac myocytes
      stimulated at 0.5 Hz and 0.2 Hz, Ca2+ entry through SL Ca2+ channels during a
      cardiac cycle was approximately 30% and approximately 50%, respectively, of the
      SR Ca2+ content. In rat myocytes Ca2+ entry via SL Ca2+ channels at 0.5 Hz was
      approximately 3.5% of the SR Ca2+ content. In the presence of 500 nM thapsigargin
      Ca2+ entry via SL Ca2+ channels in guinea pig cardiac cells was 39% greater than
      in controls, suggesting a larger contribution of this mechanism to the Ca2+
      transient when the SR is depleted of Ca2+. These results provide quantitative
      support to the understanding of the relationship between Ca2+ entry and the SR
      Ca2+ content and may help to explain differences in the Ca2+ handling observed in
      different species.

PMID- 9138578
TI  - Vibrational normal modes and dynamical stability of DNA triplex poly(dA).
      2poly(dT): S-type structure is more stable and in better agreement with
      observations in solution.
AB  - A normal-mode and statistical mechanical calculation was carried out to determine
      the vibrational normal modes, contribution of internal fluctuations to the free
      energy, and hydrogen bond disruption of DNA triplex poly(dA).2poly(dT). The
      calculation was performed on both the x-ray fiber diffraction model with a N-type
      sugar conformation, and a newly proposed model with a S-type sugar conformation.
      Our calculated normal modes for the S-type structure are in better agreement with
      observed IR spectra for samples in D2O solution. We also find that the
      contribution of internal fluctuations to free energy, premelting hydrogen bond
      disruption probability, and hydrogen bond melting temperatures for the Hoogsteen
      and Watson-Crick hydrogen bonds all show that the S-type structure is dynamically
      more stable than the N-type structure in a nominal solution environment.
      Therefore our calculation supports experimental findings that the triplex
      d(T)n.d(A)nd(T)n most likely adopts a S-type sugar conformation in solution or at
      high humidity. Our calculations, however, do not preclude the possibility of an N
      type conformation at lower humidities.

PMID- 9138579
TI  - Stretching DNA with optical tweezers.
AB  - Force-extension (F-x) relationships were measured for single molecules of DNA
      under a variety of buffer conditions, using an optical trapping interferometer
      modified to incorporate feedback control. One end of a single DNA molecule was
      fixed to a coverglass surface by means of a stalled RNA polymerase complex. The
      other end was linked to a microscopic bead, which was captured and held in an
      optical trap. The DNA was subsequently stretched by moving the coverglass with
      respect to the trap using a piezo-driven stage, while the position of the bead
      was recorded at nanometer-scale resolution. An electronic feedback circuit was
      activated to prevent bead movement beyond a preset clamping point by modulating
      the light intensity, altering the trap stiffness dynamically. This arrangement
      permits rapid determination of the F-x relationship for individual DNA molecules
      as short as -1 micron with unprecedented accuracy, subjected to both low
      (approximately 0.1 pN) and high (approximately 50 pN) loads: complete data sets
      are acquired in under a minute. Experimental F-x relationships were fit over much
      of their range by entropic elasticity theories based on worm-like chain models.
      Fits yielded a persistence length, Lp, of approximately 47 nm in a buffer
      containing 10 mM Na1. Multivalent cations, such as Mg2+ or spermidine 3+, reduced
      Lp to approximately 40 nm. Although multivalent ions shield most of the negative
      charges on the DNA backbone, they did not further reduce Lp significantly,
      suggesting that the intrinsic persistence length remains close to 40 nm. An
      elasticity theory incorporating both enthalpic and entropic contributions to
      stiffness fit the experimental results extremely well throughout the full range
      of extensions and returned an elastic modulus of approximately 1100 pN.

PMID- 9138580
TI  - Photoproducts of bacteriorhodopsin mutants: a molecular dynamics study.
AB  - Molecular dynamics simulations of wild-type bacteriorhodopsin (bR) and of its
      D85N, D85T, D212N, and Y57F mutants have been carried out to investigate possible
      differences in the photoproducts of these proteins. For each mutant, a series of
      50 molecular dynamics simulations of the photoisomerization and subsequent
      relaxation process were completed. The photoproducts can be classified into four
      distinct classes: 1) 13-cis retinal, with the retinal N-H+ bond oriented toward
      Asp-96; 2) 13-cis retinal, with the N-H+ oriented toward Asp-85 and hydrogen
      bonded to a water molecule; 3) 13,14-di-cis retinal; 4) all-trans retinal.
      Simulations of wild-type bR and of its Y57F mutant resulted mainly in class 1 and
      class 2 products; simulations of D85N, D85T, and D212N mutants resulted almost
      entirely in class 1 products. The results support the suggestion that only class
      2 products initiate a functional pump cycle. The formation of class 1 products
      for the D85N, D85T, and D212N mutants can explain the reversal of proton pumping
      under illumination by blue and yellow light.

PMID- 9138582
TI  - A new molecular model for collagen elasticity based on synchrotron X-ray
      scattering evidence.
AB  - Collagen is the most abundant structural protein in vertebrates. The specific
      shape of its stress-strain curve is crucial for the function of a number of
      organs. Although the macroscopic mechanical behavior of collagen is well known,
      there is still no explanation of the elastic process at the supramolecular level.
      We have performed in situ synchrotron x-ray scattering experiments, which show
      that the amount of lateral molecular order increases upon stretching of collagen
      fibers. In strain cycling experiments the relation between strain and diffuse
      equatorial scattering was found to be linear in the "heel" region of the stress
      strain curve. A new molecular model for collagen elasticity is proposed, which,
      based on the existence of thermally activated molecular kinks, reproduces this
      linearity and gives a simple explanation for the form of the stress-strain curve
      of collagen.

PMID- 9138581
TI  - Thermodynamic and structural analysis of microtubule assembly: the role of GTP
      hydrolysis.
AB  - Different models have been proposed that link the tubulin heterodimer nucleotide
      content and the role of GTP hydrolysis with microtubule assembly and dynamics.
      Here we compare the thermodynamics of microtubule assembly as a function of
      nucleotide content by van't Hoff analysis. The thermodynamic parameters of
      tubulin assembly in 30-100 mM piperazine-N,N'-bis(2-ethanesulfonic acid), 1 mM
      MgSO4, 2 mM EGTA, pH 6.9, in the presence of a weakly hydrolyzable analog,
      GMPCPP, the dinucleotide analog GMPCP plus 2 M glycerol, and GTP plus 2 M
      glycerol were obtained together with data for taxol-GTP/GDP tubulin assembly
      (GMPCPP and GMPCP are the GTP and GDP nucleotide analogs where the alpha beta
      oxygen has been replaced by a methylene, -CH2-). All of the processes studied are
      characterized by a positive enthalpy, a positive entropy, and a large, negative
      heat capacity change. GMPCP-induced assembly has the largest negative heat
      capacity change and GMPCPP has the second largest, whereas GTP/2 M glycerol- and
      taxol-induced assembly have more positive values, respectively. A large, negative
      heat capacity is most consistent with the burial of water-accessible hydrophobic
      surface area, which gives rise to the release of bound water. The heat capacity
      changes observed with GTP/2 M glycerol-induced and with taxol-induced assembly
      are very similar, -790 +/- 190 cal/mol/k, and correspond to the burial of 3330 +/
      820 A2 of nonpolar surface area. This value is shown to be very similar to an
      estimate of the buried nonpolar surface in a reconstructed microtubule lattice.
      Polymerization data from GMPCP- and GMPCPP-induced assembly are consistent with
      buried nonpolar surface areas that are 3 and 6 times larger. A linear enthalpy
      entropy and enthalpy-free energy plot for tubulin polymerization reactions
      verifies that enthalpy-entropy compensation for this system is based upon true
      biochemical correlation, most likely corresponding to a dominant hydrophobic
      effect. Entropy analysis suggests that assembly with GTP/2 M glycerol and with
      taxol is consistent with conformational rearrangements in 3-6% of the total amino
      acids in the heterodimer. In addition, taxol binding contributes to the
      thermodynamics of the overall process by reducing the delta H degree and delta S
      degree for microtubule assembly. In the presence of GMPCPP or GMPCP, tubulin
      subunits associate with extensive conformational rearrangement, corresponding to
      10% and 26% of the total amino acids in the heterodimer, respectively, which
      gives rise to a large loss of configurational entropy. An alternative, and
      probably preferable, interpretation of these data is that, especially with GMPCP
      tubulin, additional isomerization or protonation events are induced by the
      presence of the methylene moiety and linked to microtubule assembly. Structural
      analysis shows that GTP hydrolysis is not required for sheet closure into a
      microtubule cylinder, but only increases the probability of this event occurring.
      Sheet extensions and sheet polymers appear to have a similar average length under
      various conditions, suggesting that the minimum cooperative unit for closure of
      sheets into a microtubule cylinder is approximately 400 nm long. Because of their
      low level of occurrence, sheets are not expected to significantly affect the
      thermodynamics of assembly.

PMID- 9138583
TI  - Refractive indices of the collagen fibrils and extrafibrillar material of the
      corneal stroma.
AB  - Ultrastructural data from x-ray diffraction studies of the cornea were used to
      estimate the refractive indices of the collagen fibrils and extrafibrillar
      material of human, ox, trout, and rabbit corneas. X-ray diffraction measurements
      of the size and spacing of the collagen fibrils and the separation between the
      constituent molecules of the fibrils were taken from a previous species study.
      The tissue volume fractions occupied by the stromal components were estimated and
      their refractive indices were calculated using the Gladstone-Dale law of
      mixtures. For the fibrils and extrafibrillar material, the refractive indices in
      the human cornea were 1.411 and 1.365; for the ox 1.413 and 1.357; for the rabbit
      1.416 and 1.357; and for the trout 1.418 and 1.364, respectively. An alternative
      estimate based on the physical properties and chemical composition of bovine
      cornea, accounting for interfibrillar type VI collagen and cellular water,
      produced similar estimates of 1.416 and 1.356 for the fibrils and extrafibrillar
      material, respectively.

PMID- 9138584
TI  - Histone H1 preferentially binds to superhelical DNA molecules of higher
      compaction.
AB  - In chromatin, the physiological amount of H1 is one molecule per nucleosome or,
      roughly, one molecule per 200 bp of DNA. We observed that at such a
      stoichiometry, H1 selectively binds to supercoiled DNA with magnitude of sigma >
      or = 0.012 (both negative and positive), leaving relaxed, linear, or nicked DNA
      molecules unbound. When negative and positive DNA topoisomers of varying
      superhelicity are simultaneously present in the binding mixture, H1 selectively
      binds to the molecules with highest superhelicity; less supercoiled forms are
      gradually involved in binding upon increasing the amount of input protein. We
      explain this topological preference of H1 as the consequence of an increased
      probability for more than one H1-DNA contact provided by the supercoiling. The
      existence of simultaneous contacts of H1 with both intertwined DNA strands in the
      supercoiled DNA molecules is also inferred by topoisomerase relaxation of H1-DNA
      complexes that had been prefixed with glutaraldehyde.

PMID- 9138585
TI  - Manipulation of individual viruses: friction and mechanical properties.
AB  - We present our results on the manipulation of individual viruses using an
      advanced interface for atomic force microscopes (AFMs). We show that the viruses
      can be dissected, rotated, and translated with great facility. We interpret the
      behavior of tobacco mosaic virus with a mechanical model that makes explicit the
      competition between sample-substrate lateral friction and the flexural rigidity
      of the manipulated object. The manipulation behavior of tobacco mosaic virus on
      graphite is shown to be consistent with values of lateral friction observed on
      similar interfaces and the flexural rigidity expected for macromolecular
      assemblies. The ability to manipulate individual samples broadens the scope of
      possible studies by providing a means for positioning samples at specific binding
      sites or predefined measuring devices. The mechanical model provides a framework
      for interpreting quantitative measurements of virus binding and mechanical
      properties and for understanding the constraints on the successful,
      nondestructive AFM manipulation of delicate samples.

PMID- 9138586
TI  - Atomic force microscope measurements of long-range forces near lipid-coated
      surfaces in electrolytes.
AB  - The interaction of DMPC (L-alpha-dimyristoyl-1,2-diterradecanoyl-sn-glycero-3
      phosphoch oli ne, C36H72NO8P) lipid-coated Si3N4 surfaces immersed in an
      electrolyte was investigated with an atomic force microscope. A long-range
      interaction was observed, even when the Si3N4 surfaces were covered with
      nominally neutral lipid layers. The interaction was attributed to Coulomb
      interactions of charges located at the lipid surface. The experimental force
      curves were compared with solutions for the linearized as well as with exact
      solutions of the Poisson-Boltzmann equation. The comparison suggested that in 0.5
      mM KCl electrolyte the DMPC lipids carried about one unit of charge per 100 lipid
      molecules. The presence of this surface charge made it impossible to observe an
      effective charge density recently predicted for dipole layers near a dielectric
      when immersed in an electrolyte. A discrepancy between the theoretical results
      and the data at short separations was interpreted in terms of a decrease in the
      surface charge with separation distance.

PMID- 9138587
TI  - Measurement of inherent particle properties by dynamic light scattering:
      introducing electrorotational light scattering.
AB  - Common dynamic light scattering (DLS) methods determine the size and zeta
      potential of particles by analyzing the motion resulting from thermal noise or
      electrophoretic force. Dielectric particle spectroscopy by common microscopic
      electrorotation (ER) measures the frequency dependence of field-induced rotation
      of single particles to analyze their inherent dielectric structure. We propose a
      new technique, electrorotational light scattering (ERLS). It measures ER in a
      particle ensemble by a homodyne DLS setup. ER-induced particle rotation is
      extracted from the initial decorrelation of the intensity autocorrelation
      function (ACF) by a simple optical particle model. Human red blood cells were
      used as test particles, and changes of the characteristic frequency of membrane
      dispersion induced by the ionophore nystatin were monitored by ERLS. For
      untreated control cells, a rotation frequency of 2 s-1 was induced at the
      membrane peak frequency of 150 kHz and a field strength of 12 kV/m. This rotation
      led to a decorrelation of the ACF about 10 times steeper than that of the field
      free control. For deduction of ERLS frequency spectra, different criteria are
      discussed. Particle shape and additional field-induced motions like
      dielectrophoresis and particle-particle attraction do not significantly influence
      the criteria. For nystatin-treated cells, recalculation of dielectric cell
      properties revealed an ionophore-induced decrease in the internal conductivity.
      Although the absolute rotation speed and the rotation sense are not yet directly
      accessible, ERLS eliminates the tedious microscopic measurements. It offers
      computerized, statistically significant measurements of dielectric particle
      properties that are especially suitable for nonbiological applications, e.g., the
      study of colloidal particles.

PMID- 9138588
TI  - Modification of calcite crystal growth by abalone shell proteins: an atomic force
      microscope study.
AB  - A family of soluble proteins from the shell of Haliotis rufescens was introduced
      over a growing calcite crystal being scanned in situ by an atomic force
      microscope (AFM). Atomic step edges on the crystal surface were altered in shape
      and speed of growth by the proteins. Proteins attached nonuniformly to the
      surface, indicating different interactions with crystallographically different
      step edges. The observed changes were consistent with the habit modification
      induced by this family of proteins, as previously observed by optical microscopy.
      To facilitate further studies in this area, AFM techniques and certain AFM
      imaging artifacts are discussed in detail.

PMID- 9138589
TI  - Micropipette aspiration of human erythrocytes induces echinocytes via membrane
      phospholipid translocation.
AB  - When a discocytic erythrocyte (RBC) was partially aspirated into a 1.5-microns
      glass pipette with a high negative aspiration pressure (delta P = -3.9 kPa), held
      in the pipette for 30 s (holding time, th), and then released, it underwent a
      discocyte-echinocyte shape transformation. The degree of shape transformation
      increased with an increase in th. The echinocytes recovered spontaneously to
      discocytes in approximately 10 min, and there was no significant difference in
      recovery time at 20.9 degrees C, 29.5 degrees C, and 37.4 degrees C,
      respectively. At 11 degrees C the recovery time was significantly elevated to
      40.1 +/- 6.7 min. At 20.9 degrees C the shape recovery time varied directly with
      the isotropic RBC tension induced by the pipetting. Sodium orthovanadate
      (vanadate, 200 microM), which inhibits the phospholipid translocase, blocks the
      shape recovery. Chlorpromazine (CP, 25 microM) reversed the pipette-induced
      echinocytic shape to discocytic in < 2 min, and the RBC became a
      spherostomatocyte-II after another 30 min. It was hypothesized that the increase
      in cytosolic pressure during the pipette aspiration induced an isotropic tension
      in the RBC membrane followed by a net inside-to-outside membrane lipid
      translocation. After a sudden release of the aspiration pressure the cytosolic
      pressure and the membrane tension normalized immediately, but the translocated
      phospholipids remained temporarily "trapped" in the outer layer, causing an area
      excess and hence the echinocytic shape. The phospholipid translocase activity,
      when not inhibited by vanadate, caused a gradual return of the translocated
      phospholipids to the inner layer, and the RBC shape recovered with time.

PMID- 9138590
TI  - Odorant-induced currents in intact patches from rat olfactory receptor neurons:
      theory and experiment.
AB  - Odorant-induced currents in mammalian olfactory receptor neurons have proved
      difficult to obtain reliably using conventional whole-cell recording. By using a
      mathematical model of the electrical circuit of the patch and rest-of-cell, we
      demonstrate how cell-attached patch measurements can be used to quantitatively
      analyze responses to odorants or a high (100 mM) K+ solution. High K+ induced an
      immediate current flux from cell to pipette, which was modeled as a
      depolarization of approximately 52 mV, close to that expected from the Nernst
      equation (56 mV), and no change in the patch conductance. By contrast, a cocktail
      of cAMP-stimulating odorants induced a current flux from pipette into cell
      following a significant (4-10 s) delay. This was modeled as an average patch
      conductance increase of 36 pS and a depolarization of 13 mV. Odorant-induced
      single channels had a conductance of 16 pS. In cells bathed with no Mg2+ and 0.25
      mM Ca2+, odorants induced a current flow from cell to pipette, which was modeled
      as a patch conductance increase of approximately 115 pS and depolarization of
      approximately 32 mV. All these results are consistent with cAMP-gated cation
      channels dominating the odorant response. This approach, which provides useful
      estimates of odorant-induced voltage and conductance changes, is applicable to
      similar measurements in any small cells.

PMID- 9138591
TI  - Calcium dynamics associated with a single action potential in a CNS presynaptic
      terminal.
AB  - Calcium dynamics associated with a single action potential were studied
      quantitatively in the calyx of Held, a large presynaptic terminal in the rat
      brainstem. Terminals were loaded with different concentrations of high- or low
      affinity Ca2+ indicators via patch pipettes. Spatially averaged Ca2+ signals were
      measured fluorometrically and analyzed on the basis of a single compartment
      model. A single action potential led to a total Ca2+ influx of 0.8-1 pC. The
      accessible volume of the terminal was about 0.4 pl; thus the total calcium
      concentration increased by 10-13 microM. The Ca(2+)-binding ratio of the
      endogenous buffer was about 40, as estimated from the competition with Fura-2,
      indicating that 2.5% of the total calcium remained free. This is consistent with
      the peak increase in free calcium concentration of about 400 nM, which was
      measured directly with MagFura-2. The decay of the [Ca2+]i transients was fast,
      with time constants of 100 ms at 23 degrees C and 45 ms at 35 degrees C,
      indicating Ca2+ extrusion rates of 400 and 900 s-1, respectively. The combination
      of the relatively low endogenous Ca(2+)-binding ratio and the high rate of Ca2+
      extrusion provides an efficient mechanism for rapidly removing the large Ca2+
      load of the terminal evoked by an action potential.

PMID- 9138592
TI  - Neutrophil motility in extracellular matrix gels: mesh size and adhesion affect
      speed of migration.
AB  - Polymorphonuclear leukocyte (PMN) migration through tissue extracellular space is
      an essential step in the inflammatory response, but little is known about the
      factors influencing PMN migration through gels of extracellular matrix (ECM). In
      this study, PMN migration within reconstituted gels containing collagen type I or
      collagen type I supplemented with laminin, fibronectin, or heparin was measured
      by quantitative direct visualization, resulting in a random motility coefficient
      (mum a quantitative index for rate of cell dispersion) for the migrating cell
      population. The random motility coefficient in unsupplemented collagen (0.4
      mg/ml) gels was approximately 9 x 10(-9) cm2/s. Supplementing gels with heparin
      or fibronectin produced a significant decrease in mu, even at the lowest
      concentrations studied (1 microgram/ml fibronectin or 0.4 microgram/ml heparin).
      At least 100 micrograms/ml of laminin, or 20% of the total gel protein, was
      required to produce a similar decrease in mu. Scanning electron microscopy
      revealed two different gel morphologies: laminin or fibronectin appeared to coat
      the 150-nm collagen fibers whereas heparin appeared to induce fiber bundle
      formation and, therefore, larger interstitial spaces. The decrease in mu observed
      in heparin-supplemented gels correlated with the increased mesh size of the fiber
      network, but the difference observed in mu for fibronectin- and laminin
      supplemented gels did not correlate with either mesh size or the mechanical
      properties of the gel, as determined by rheological measurements. However, PMNs
      adhered to fibronectin-coated surfaces in greater numbers than to collagen- or
      laminin-coated surfaces, suggesting that changes in cell adhesion to protein
      fibers can also produce significant changes in cell motility within an ECM gel.

PMID- 9138593
TI  - Linker histones' role revisited.

PMID- 9138594
TI  - Smooth and skeletal muscle single-molecule mechanical experiments.

PMID- 9138595
TI  - Why do cyclic nucleotide-gated channels have the jitters?

PMID- 9138596
TI  - A closer look at a molecular motor by atomic force microscopy.

PMID- 9138597
TI  - Mechanisms of sodium/calcium selectivity in sodium channels probed by cysteine
      mutagenesis and sulfhydryl modification.
AB  - A conserved lysine residue in the "P loop" of domain III renders sodium channels
      highly selective. Conversion of this residue to glutamate, to mimic the
      homologous position in calcium channels, enables Ca2+ to permeate sodium
      channels. Because the lysine-to-glutamate mutation converts a positively charged
      side chain to a negative one, it has been proposed that a positive charge at this
      position suffices for Na+ selectivity. We tested this idea by converting the
      critical lysine to cysteine (K1237C) in mu 1 rat skeletal sodium channels
      expressed in Xenopus oocytes. Selectivity of the mutant channels was then
      characterized before and after chemical modification to alter side-chain charge.
      Wild-type channels are highly selective for Na+ over Ca2+ (PCa/PNa < 0.01). The
      K1237C mutation significantly increases permeability to Ca2+ (PCa/PNa = 0.6) and
      Sr2+. Analogous mutations in domains I (D400C), II (E755C), and IV (A1529C) did
      not alter the selectivity for Na+ over Ca2+, nor did any of the domain IV
      mutations (G1530C, W1531C, and D1532C) that are known to affect monovalent
      selectivity. Interestingly, the increase in permeability to Ca2+ in K1237C cannot
      be reversed by simply restoring the positive charge to the side chain by using
      the sulfhydryl modifying reagent methanethiosulfonate ethylammonium. Single
      channel studies confirmed that modified K1237C channels, which exhibit a reduced
      unitary conductance, remain permeable to Ca2+, with a PCa/PNa of 0.6. We conclude
      that the chemical identity of the residue at position 1237 is crucial for channel
      selectivity. Simply rendering the 1237 side chain positive does not suffice to
      restore selectivity to the channel.

PMID- 9138598
TI  - The ATP-binding site of Ca(2+)-ATPase revealed by electron image analysis.
AB  - The location of the ATP-binding site of a P-type ion pump, Ca(2+)-ATPase from
      rabbit sarcoplasmic reticulum, was examined by cryoelectron microscopy. A
      nonhydrolyzable analog of ATP, beta, gamma-bidentate chromium (III) complex of
      ATP (CrATP), was used to stabilize the enzyme in the Ca(2+)-occluded state.
      Tubular crystals were then induced by vanadate in the presence of EGTA, keeping
      CrATP bound to the enzyme. The three-dimensional structures of the crystals were
      determined at 14 A resolution by cryoelectron microscopy and helical image
      analysis. Statistical comparison of the structures with and without CrATP showed
      clear and significant differences at the groove proposed previously as the ATP
      binding pocket.

PMID- 9138599
TI  - Modulation by lonidamine on the combined activity of cisplatin and epidoxorubicin
      in human breast cancer cells.
AB  - The ability of lonidamine (LND), an energolytic derivative of indazole-carboxylic
      acid, to modulate the cytotoxic activity of cisplatin (CDDP) and epidoxorubicin
      (EPI), singly or in combination, was investigated in two human breast cancer cell
      lines (MCF7 and T47D). A 72-hr post-incubation with a non-cytotoxic concentration
      of LND (75 microM) increased the activity of a 1-hr CDDP treatment as well as
      that of a 1 to 16-hr EPI treatment. A different pattern of interaction among the
      drugs and modulator was observed as a function of the sequence of drug treatment.
      Specifically, supra-additive or additive effects of the combination were obtained
      in the two cell lines according to the different treatment schemes. In
      particular, the maximum potentiation was observed in MCF7 cells simultaneously
      exposed to CDDP, EPI and LND for 1 hr and then post-incubated with LND for 72 hr,
      and in T47 first exposed to EPI and LND, then to CDDP and LND, and finally post
      incubated with LND. Flow cytometric analysis of MCF7 cell distribution in the
      different cycle phases showed that combined treatment with EPI/CDDP/LND was able
      to stabilize cell cycle perturbations (mainly G2M accumulation) induced by
      individual agents. The ability of LND to potentiate CDDP and EPI cytotoxicity,
      and the consideration that LND causes side effects different from those caused by
      alkylating agents and anthracyclines, make this compound an attractive candidate
      for multidrug combination therapy in breast cancer.

PMID- 9138601
TI  - Breast cancer stage at diagnosis: Caucasians versus Hispanics.
AB  - In the Department of Defense health care system, all women have the same ability
      to access health care. Thus, there should be no racial differences in stage at
      diagnosis solely based on ability to seek health care. A retrospective review of
      breast cancer cases from 1980-1992 was conducted to determine if there were any
      differences in stage at diagnosis between Caucasian and Hispanic females. Data
      was available for 6134 Caucasian and 182 Hispanic females. Although not
      statistically significant, Hispanic females had fewer Stage I (41% versus 53%)
      and more Stage IIA (37% versus 28%) breast cancers than Caucasian females.
      Hispanic females had statistically fewer tumors < or = 1 cm (p < 0.001).
      Caucasian females were older (median age 58 years) at presentation than Hispanic
      females (median age 51 years). Significantly (p = 0.002) more Hispanic females
      (44%) were < 50 years old compared to Caucasian females (28%). When access to
      care is not an issue, Hispanic females tended to present at a more advanced stage
      although this did not reach statistical significance. Hispanic females with
      breast cancer were significantly younger than Caucasian females.

PMID- 9138600
TI  - Macromolecular interstitial clearance, tumour vascularity, other prognostic
      factors and breast cancer survival.
AB  - BACKGROUND: Clearance of large molecules from the interstitial space is an
      important function of lymphatics and is affected by local pathologic changes.
      OBJECTIVE: To determine if the clearance rate of interstitially injected albumin
      is correlated to tumour characteristics and outcome in women with invasive breast
      cancer. METHOD: In a consecutive series of women coming to biopsy for suspected
      breast cancer, technetium-tagged albumin was injected into the tissue adjacent to
      the palpable mass. The isotope disappearance rate was measured over two hours.
      Also assessed were the maximum vessel density (MVD-using Factor VIII polyclonal
      antisera), the proliferation rate (using Ki-67 antisera), node status, tumour
      size, histologic and nuclear grade, mitotic rate, and p53 and c-erbB-2
      oncoproteins. All patients were followed until relapse and for a minimum of 10
      years. RESULTS: In multivariate analysis, an association between relapse-free
      survival and isotope clearance rate was suggested (p = 0.024). The best outcome
      was seen in patients with the least isotope clearance. Node status, size,
      histologic and nuclear grade, and mitotic rate correlated with survival. MVD did
      not correlate with survival and was inversely related to the isotope clearance
      rate. Tumour proliferation rate, and the c-erbB-2 and p53 oncoproteins did not
      relate to outcome. CONCLUSION: The role of lymphatics in breast cancer is
      difficult to study. Measurement of interstitial clearance may be a useful
      technique and could be a prognostic factor.

PMID- 9138602
TI  - Inhibition of hormone and growth factor responsive and resistant human breast
      cancer cells by CeReS-18, a cell regulatory sialoglycopeptide.
AB  - We have previously documented that CeReS-18, a cell regulatory sialoglycopeptide,
      inhibits the cellular proliferation of normal and transformed cell types from a
      diverse range of species. Most cell types studies exhibit a similar sensitivity
      to the reversible but growth inhibitory effects of CeReS-18 at 7 x 10(8) M
      concentration, while at higher concentrations CeReS-18 can elicit cytotoxicity.
      The present study was conducted to examine the effect of CeReS-18 on the
      proliferation of human mammary epithelial carcinoma cells. MCF-7 cells, which are
      estrogen receptor positive (ER+), and BT-20 cells, which are estrogen receptor
      negative (ER+), were utilized. Both cell lines show equal sensitivity to growth
      inhibition elicited by CeReS-18. Complete cessation of cell cycling was achieved
      with 7 x 10(-8) M CeReS-18, and the arrest was shown to be completely reversible.
      Flow cytometric analysis, performed on CeReS-18 treated cells from both cell
      types, revealed that the majority of these cells were arrested in the G1 phase of
      the cell cycle. When cells were treated simultaneously with inhibitor and
      stimulatory concentrations of mitogens such as epidermal growth factor (EGF),
      basic fibroblast growth factor (b-FGF), estrogen, insulin-like growth factors I
      and II (IGFI and IGFII), no alteration of the inhibitory activity of CeReS-18 was
      observed. CeReS-18 clearly abrogated the mitogenic activity that these growth
      factors elicited with human mammary carcinoma cells.

PMID- 9138603
TI  - CeReS-18, a novel cell surface sialoglycopeptide, induces cell cycle arrest and
      apoptosis in a calcium-sensitive manner.
AB  - Very few growth inhibitors have been identified which can inhibit the
      proliferation of a broad spectrum of human breast cancer cell lines. CeReS-18, a
      novel cell surface sialoglycopeptide growth inhibitor, can reversibly inhibit the
      proliferation of both estrogen receptor positive (MCF-7) and negative (BT-20)
      human breast cancer cell lines. In addition, at concentrations above those
      required for the reversible inhibition of cell proliferation, CeReS-18 can also
      induce cell death in MCF-7 cells. Changes in nuclear and cytoplasmic morphology,
      characteristic of apoptosis, were detected in MCF-7 cells treated with a
      cytotoxic concentration of CeReS-18, and internucleosomal DNA cleavage was also
      observed. The sensitivity of MCF-7 and BT-20 cells to the biological properties
      of CeReS-18 could be influenced by altering the calcium concentration in the
      extracellular growth medium, such that when the calcium concentration in the
      environment was decreased, and increased sensitivity to CeReS-18-induced growth
      inhibition and cytotoxicity were observed. The addition of the calcium chelating
      agent EGTA to MCF-7 cells, cultured in a normal calcium environment, could mimic
      the increased sensitivity to the biological effects of CeReS-18 observed under
      reduced calcium conditions.

PMID- 9138604
TI  - Validation of existing and development of new prognostic classification schemes
      in node negative breast cancer. German Breast Cancer Study Group.
AB  - Several prognostic classification schemes in node negative breast cancer are
      proposed, but only the Nottingham Prognostic Index (NPI) seems to be sufficiently
      validated. Validation, which is a prerequisite for a sensible assessment, is not
      published for two recent proposals according to Glick et al. [1] and Rubens [2].
      The German Breast Cancer Study Group (GBSG) entered 662 eligible patients in a
      prospective observational study. 603 of them had complete data for seven
      'standard' prognostic factors and median follow-up is about 5 years. As there is
      no accepted and informative measure of separation for classification schemes
      presently available, we propose a new one and use it additionally to the well
      known logrank-test and Kaplan-Meier estimates to investigate the predictive power
      of the three schemes. significant differences in survival and recurrence-free
      survival could be established for the NPI subgroups but not for others where even
      the ordering of the groups was different. With the Cox model and the
      classification and regression tree approach we develop two new proposals for the
      differentiation of subgroups of node negative patients. As in the NPI, tumor size
      and grade are the most important factors, but with a different weighting scheme.
      Young age (< or = 40 years) and very high estrogen receptor values (> 300 fmol)
      in a small subgroup of patients were associated with worse prognosis. The new
      proposals showed a better degree of separation, which demonstrates that an
      improvement seems possible using standard factors. Because the measures of
      separation give an overoptimistic impression for the new proposals, a validation
      with other studies is necessary before a general recommendation can be given.

PMID- 9138605
TI  - Influence of investigator experience and microscopic field size on microvessel
      density in node-negative breast carcinoma.
AB  - In this study on the determination of intratumoral microvessel density (MVD) in
      breast cancer, we have investigated the influence of the observer experience and
      the microscopic field size. We have used the sample set reported on earlier in
      the J Natl Cancer Inst 87: 1797-1798, 1995. This case-control study has shown a
      positive association of high MVD and unfavorable outcome when comparing node
      negative pT1-2 breast carcinoma (NNBC) patients with a disease-free period of
      over ten years with those with an early distant relapse. Tumor sections of both
      outcome groups (favorable: n = 19; unfavorable: n = 19) were immunostained for
      factor VIII related-antigen (FVIII r-Ag). Microvessels were counted in the areas
      of most intense vascularization ('hot spots'), both at magnification x 200 (field
      size of 0.61 square mm) and x 400 (field size of 0.15 square mm), by one
      inexperienced and three experienced observers. Microphotographs of individual
      vascular hot spots were analyzed using overlays resembling the two field sizes.
      The main results obtained are: i) a confirmation of the prognostic value of
      microvessel density in the case-control sample set (n = 38) was established by
      all experienced but not by the unexperienced investigator; ii) both at x 200 and
      x 400 magnification, angiogenesis quantification in vascular hot spots contained
      prognostic information. The results of this study indicate that the selection of
      vascular hot spots in tumor sections immunostained for an antigen expressed on
      endothelial cells is more prone to inter-observer variability and more dependent
      on training than the counting of the microvessels within predefined hot spots
      itself. The microscopic magnification and resulting field size do not influence
      the prognostic significance of MVD in NNBC. This information validates the
      development of more objective methods of measuring the amount of angiogenesis
      within malignant tissue. This will allow more accurate implementation of the
      angiogenesis parameter in multiparametric and prospective prognostic factor
      studies in NNBC.

PMID- 9138606
TI  - Clinical significance of bcl-2 gene expression in human breast cancer tissues.
AB  - The expression of estrogen receptor (ER) and bcl-2 (Bcl-2), an apoptosis
      protective oncogene, in normal and cancerous breast duct epithelia was
      immunohistochemically examined in fresh frozen tumor tissues from 142 Japanese
      breast cancer patients. The clinico-pathological characteristics and the disease
      free survival of the patients were analyzed. The expression of both the proteins
      was also observed in intraductal components of breast cancer. Although less than
      1% of normal duct epithelia expressed ER, Bcl-2 was diffusely expressed. The
      expression of both these proteins in breast cancer significantly correlated with
      each other. Their expression significantly correlated negatively with tumor size
      but not with lymph node status. The papillo-tubular sub-type of invasive ductal
      carcinoma expressed Bcl-2 significantly more frequently than the solid-tubular
      sub-type. Patients with Bcl-2 expressing tumors survived without recurrence
      significantly more than those with tumors exhibiting reduced expression.
      Papillary-cribriform type intraductal components expressed both those proteins
      more often than the solid-comedo type.

PMID- 9138607
TI  - Phase II study of vinorelbine and ifosfamide in anthracycline resistant
      metastatic breast cancer.
AB  - The new combination of ifosfamide and vinorelbine was evaluated in a phase II
      study of patients with metastatic breast cancer. All the patients had evaluable
      or measurable lesions resistant to the combination of cyclophosphamide,
      epidoxorubicin and 5-fluorouracil. Out of 25 patients entered the trial, 7
      achieved an objective response (28%) (95% C.I. 12-49.3). Ten patients (40%)
      experienced stable disease and the remaining patients (30%) progressive disease.
      The median time to progression was 4 months (range 2-12+). The activity of the
      ifosfamide-vinorelbine combination has been demonstrated and the toxicity was
      acceptable.

PMID- 9138608
TI  - Seasonal trends in the self-detection of breast cancer: indications from the
      Cancer and Steroid Hormone (CASH) study.
AB  - Of 2895 women who self-detected an incident breast cancer that required surgery,
      peaks in month of detection occurred in spring and late autumn (p = 0.012). For
      the subset of cases for whom receptor status was available, there was a highly
      significant seasonal variation in detection only for those with ER-negative
      tumors. Further investigations into seasonality and breast cancer detection may
      be warranted.

PMID- 9138609
TI  - TGF-beta 1 mRNA expression in clinical breast cancer and its relationship to ER
      mRNA expression.
AB  - Eighty nine primary breast cancers were investigated for the expression of TGF
      beta 1 and ER mRNA using PCR of reverse transcribed RNA. PCR products were
      validated using Southern blots and hybridization with radiolabelled cDNA probes.
      TGF beta 1 mRNA was found to be expressed in 56/89 (63%) of the breast cancers
      while ER mRNA was expressed in 23/89 (26%) of the tumours. Using chi-square
      analysis TGF-beta mRNA expression was found to correlate significantly with ER
      mRNA expression (p < 0.001), in that virtually all tumours that expressed ER mRNA
      co-expressed TGF beta 1. In tumours that were ER mRNA negative, TGF beta 1
      expression was more variable. These results suggest that during tumour
      progression, ER expression is lost more frequently than is growth factor
      expression.

PMID- 9138610
TI  - Classification of non-Hodgkin's lymphomas.

PMID- 9138611
TI  - Practical role of molecular diagnostics in non-Hodgkin's lymphomas.
AB  - Molecular techniques are becoming increasingly important in the analysis of NHL,
      both for diagnostic purposes and in order to evaluate prognosis accurately. The
      increasing number of techniques available renders evaluation of their relative
      roles important and a review of their informativity in NHL at diagnosis timely.
      Molecular equivalents of chromosomal translocations generate either a qualitative
      change due to the expression of a chimaeric, relatively tumour specific, protein,
      such as the NPM-ALK associated with the t(2;5) in ALCL or a quantitative change
      in the extent, stage or site of expression of a full length protein, due to its
      juxtapositioning to and deregulation by an Ig or TCR gene. The latter represents
      errors of the somatic recombination process which lymphoid precursors undergo. In
      NHL, this category includes BCL1/CCND1, BCL2, BCL6 and MYC. The molecular
      characteristics, the functional consequences and the main clinical correlations
      of each of these abnormalities is reviewed. At diagnosis, immunological detection
      of the deregulated 'protooncogene' may well provide the simplest, most
      appropriate screening technique for CCND1 and NPM-ALK induced ALK expression.
      BCL6 abnormalities demonstrate similarities to BCL2 and MYC and a combination of
      immunophenotypic, FISH, Southern blot and PCR techniques are useful in their
      characterization. For the approximately 50% of NHL without one of the above
      markers, identification of a clonal Ig or TCR rearrangement can provide a useful
      'pan' B or T molecular equivalent, provided that the limitations of the detection
      techniques are appreciated. Appropriate use of these techniques will transform
      our ability to classify, stratify and eventually treat in a risk adapted manner,
      patients with NHL.

PMID- 9138612
TI  - Management of histologically indolent non-Hodgkin's lymphomas.
AB  - Histologically indolent lymphomas which represent 40-50% of all non-Hodgkin's
      lymphomas encompass small lymphocytic lymphomas, follicular lymphomas and other
      entities more recently described such as mantle cell and marginal zone lymphomas.
      Their management has benefited from new drugs such as interferon alpha the purine
      analogues and new treatment modalities especially autologous stem cell
      transplantation.

PMID- 9138613
TI  - Management of the histologically aggressive non-Hodgkin's lymphomas in adults.
AB  - The understanding of lymphocyte biology and lymphomagenesis has increased
      dramatically in the past two decades, but this has not been matched by rapid
      advances in therapy. There have been numerous false dawns and these serve to
      emphasize the importance of large randomized trials. Increasingly, therapy must
      be designed for specific subgroups of patients, this making it difficult to
      perform large trials and accentuating the need for multicentre collaboration.

PMID- 9138614
TI  - Management of histologically aggressive lymphomas with a high risk of CNS
      disease.
AB  - The NHLs are a group of neoplasms that share a common target tissue, and are
      characterized by a high degree of biological and clinical heterogeneity. Adult
      lymphomas with a high propensity for CNS involvement comprise SNCC, lymphoma
      (ATLL), LL, and PCL of immunocompromised patients. Despite recently reported
      encouraging results, there is no standard therapy available for ATLL or PCL. In
      contrast, recent data from several groups suggest that the therapeutic outcome of
      SNCC lymphoma in adults is similar to the excellent results in children, when the
      same regimens are used, and the toxicity, at least for adults less than 60 years,
      is also similar. Although more intensive chemotherapy combined with CNS
      prophylaxis has extended the long-term survival of patients with LL, the
      treatment results in adults fall short of those for children.

PMID- 9138615
TI  - Gut lymphomas.
AB  - Gut lymphoma still remains the subject of much debate and controversy with
      respect to pathological classification, clinical staging and treatment. This is
      mainly due to the fact that most studies reported retrospective non-randomized
      evaluations of small series and lacked uniformity in histological classification,
      patients' characteristics and type of treatment. Moreover, most of the historical
      series were published before the recognition of MALT as the origin of most GI
      lymphomas. Hence, there is a compelling need for the use of modern histological
      criteria for primary GI lymphomas because of their unique histology, special
      features and origin in mucosal tissue. General adoption of the histological
      classification proposed in 1988 by Isaacson et al (Table 1) can be recommended
      which follows the general principles of the Kiel Classification and includes the
      MALT lymphomas as a particular disease entity. Combination chemotherapy is the
      treatment of choice for gut lymphomas with aggressive histology and multiple node
      involvement or disseminated disease. The effectiveness of combination
      chemotherapy in advanced disease has excited a reconsideration of the role of
      primary surgery in less advanced cases where surgery has, historically, been the
      initial procedure of choice. This is particularly true for gastric lymphomas
      where it is possible that, in future, surgery will be resorted to as a potential
      approach for salvage when complete remission is not achieved with conservative
      therapy. For primary intestinal lymphoma, however, there are as yet no studies
      which clearly demonstrate that surgery is not necessary. With respect to the
      group of localized low-grade MALT lymphomas of the stomach and the indolent
      nature of the disease make plausible a conservative approach, with antibiotic
      eradication of H. pylori as the sole initial treatment. This may avert or at
      least postpone the indication for surgical resection in the majority of patients.

PMID- 9138616
TI  - Management of cutaneous lymphoma.
AB  - The foregoing underlines the advances which have been made in our understanding
      of cutaneous lymphoma and the areas where further research is needed. With a few
      noteable exceptions the aim of therapy in CTCL is palliative rather than curative
      and treatment success is measured in terms of disease-free interval. There is
      still no evidence that any chemotherapeutic regimen prolongs survival. A possible
      exception is the effect of photopheresis in Sezary syndrome but our own
      experience differs from that in the USA and underlines the need to identify
      patients with clonal disease when defining subjects for study. The combination of
      genotypic analysis and new treatment methods offers exciting new prospects in the
      management of patients with cutaneous lymphoma.

PMID- 9138617
TI  - Management of paediatric lymphoma.
AB  - The high cure rate obtained in most paediatric lymphomas allows an optimistic
      vision of future treatments, with decreased primary late effects observed in
      patients who have completed therapy: decreased cognitive functional impairment,
      reproductive dysfunction, poor social adaptation, and risk of second
      malignancies. The deleterious effects of radiation therapy on neurocognitive
      functions is now well documented (Meadows et al, 1981) but, apart from rare acute
      toxicities (Sasazaki et al, 1992), reports on those following high-dose
      methotrexate are scarce, and sometimes discordant (Jannoun and Chessels, 1987;
      Robertson et al, 1992). Longer follow-up evaluation is warranted before
      definitive conclusions concerning the relationship between computed tomography
      scan findings and clinical outcome can be reached. The reproductive function of
      males is much more severely altered than that of females (Jaffe et al, 1988).
      Several reports have demonstrated the major dose-dependent toxicity of alkylating
      agents on male fertility. Male patients receiving more than 9 g/m2 of
      cyclophosphamide have a particularly high risk of sterility (Aubier et al, 1989)
      and children with less than 4 g/m2 of cyclophosphamide, a very low risk Patte et
      al, 1996a). Women treated before the age of 20 who do not receive abdominal
      irradiation usually have normal reproductive function, although early puberty
      (Quigley et al, 1989) and early menopause (Byrne et al, 1992) have been
      documented. The risk of a second malignancy is not as great as in children with a
      solid tumour or Hodgkin's disease (Anderson et al, 1993). The risk is higher in
      patients treated with alkylating agents (Lemerle et al, 1989). With the
      increasing cure rate, a social problem may arise for adults who "have had
      cancer'. The increased awareness by politicians and health insurance companies
      should help to solve, at least partially, this new problem (Monaco, 1987). As
      cure rates increase, emerging concerns involve the familial repercussions of this
      heavy treatment (Lansky et al, 1978; Cairns et al, 1979). At this stage, there is
      no demonstrated deleterious effect from treatment for the progeny of cured
      children (Mulvihill et al, 1987; Stein, 1993). Cure of children with lymphoma is
      a reality, and one should think in terms of "complete cure' when facing a
      distressed child with a heavy tumour burden arriving for diagnosis (Schweisguth,
      1979). Since 1980, the progress of molecular biology techniques has permitted the
      precise molecular characterization of gene alterations (oncogenes,
      immunoglobulins, and T-cell receptor genes) involved in the process of malignant
      transformation of normal lymphocytes (Bhatia et al, 1996; Williams et al, 1996).
      In parallel, treatment of malignant NHL of childhood has improved dramatically.
      The progress in molecular biology has not led to a modification of the clinical
      management of NHL of childhood which remains mainly empirical. Precise
      cytohistological classification of lymphomas has resulted in the characterization
      of low- and high-risk patients requiring distinct therapeutic approaches. The
      major goals of the next few years will be to increase the cure rates of those
      patients with CNS and bone marrow involvement at diagnosis, probably through an
      intensification of chemotherapy (increase in the dose or intensity of the
      chemotherapy); to define precisely subgroups of good-prognosis patients requiring
      less aggressive treatment that would decrease the risk of long-term events; and
      to salvage previously heavily treated patients at relapse. The precise analysis
      of gene alterations in lymphoma cells of a given patient may have important
      clinical applications in this respect (Bhatia et al, 1996).

PMID- 9138618
TI  - Vaccine strategies in non-Hodgkin's lymphomas.
AB  - As described above, the most recent advances in anti-idiotype vaccination
      strategies have gone hand in hand with recent developments in molecular biology
      and other forms of cancer therapy. The techniques that are currently available in
      antibody engineering will greatly facilitate protein production and purification
      and will reduce the time and effort needed to produce the patient specific
      vaccines. Cytokine (gene) therapy has extensively been studied in cancer
      treatment and cancer vaccination and some therapeutic strategies are currently
      being evaluated in clinical trials (Bubenik, 1996). Combination therapy of
      idiotypic vaccination with cytokine therapy has recently been explored with
      promising results. The main focus so far has been on GM-CSF and IL-2, although
      other cytokines might prove to be efficient in stimulating different effector
      arms of the immune system. The nature of the immune response mounted by the host
      against the tumour and the mechanisms by which the tumour cells escape the
      effector functions of the immune system are not yet fully known. A better
      knowledge of the nature of B-cell lymphomas and the relation to the patient's
      immune system will therefore benefit the further development of the therapeutic
      strategies. Further research will provide us with a better view of how to break
      the immune tolerance and of which components of the immune system have to be
      targeted in order to obtain optimal therapeutic results.

PMID- 9138619
TI  - Anti-sense and gene therapy approaches to the treatment of lymphomas.
AB  - The availability of molecular genetic technology has opened up a large range of
      potential strategies for the treatment of lymphoma. In the immediate future it is
      likely that these techniques will be of most use in the evaluation of procedures
      such as purging, ex vivo expansion of haemopoietic progenitors and adoptive
      immunotherapy. On the horizon however are strategies such as anti-sense, immune
      gene therapy and stem cell protection which may prove valuable adjuncts to our
      existing therapeutic armoury. The pace of developments in this field is such that
      long-term predictions are unlikely to be accurate but it seems certain that this
      whole area will continue to grow rapidly.

PMID- 9138620
TI  - Performance of HTLV-1 screening assays in Brazil.
AB  - In recent years a variety of studies have been carried out to compare the
      accuracy (generally expressed in terms of sensitivity and specificity) of
      commercially available anti-HTLV tests. None of these studies were performed in
      Brazil or in any other South American country. During the characterization of our
      Brazilian reference panel we evaluated the sensitivities and specificities of the
      Abbott HTLV EIA (100%; 89.7%) and the Biochrom HTLV-1/-2 ELISA (100%; 42.4%). Our
      conclusion was that both assays may be problematic in terms of correctly
      identifying HTLV-negative sera. We therefore adjusted the cut-off values using
      receiver operating characteristics (ROC). ROC analysis, which involves
      calculating sensitivity and specificity for several cut-off values, can be used
      to ascertain the co-variation in the specificity and sensitivity of any assay
      giving quantitative results. The optimum cut-off value for the assay in a given
      study population is the point that gives highest possible sensitivity in
      conjunction with a small false-positive fraction. Using the HTLV-1/-2 Western
      blot as the "gold standard", we were able to improve the specificity of the
      Biochrom HTLV-1/-2 assay to 95% without affecting its sensitivity of 100%.
      However, it seems that when using the Biochrom HTLV-1/-2 ELISA, there may be
      problems in separating positive and negative sera. In the case of the Abbott HTLV
      EIA, our ROC analysis revealed that the cut-off value suggested by the
      manufacturer was nearly identical to the optimum cut-off value. Adjustment will
      affect neither sensitivity nor specificity. However, a slight adjustment of the
      cut-off value result in a clearer separation of the positive and negative
      populations. Furthermore, we assume that this adjustment will help to avoid false
      positive results when larger serum panels are investigated. Further
      investigations will show whether or not this problem is linked to the
      geographical regions where the test is performed (e.g. polyclonal stimulation due
      to parasitic infections in tropical countries).

PMID- 9138622
TI  - Genetics and behavioral medicine: the error of the error term.

PMID- 9138621
TI  - Genetics and behavioral medicine: risk factors for cardiovascular disease.
AB  - This is the second in a series of three articles addressing the intersection of
      interests in behavioral genetics and behavioral medicine. In this article, we use
      risk factors for cardiovascular disease as a prototypical trait for which
      behavioral genetic approaches provide powerful tools for understanding how risk
      factors, behavior, and health outcomes are related. The approach synthesizes a
      number of methods and areas of interest in an attempt to arrive at a
      comprehensive, whole-organism understanding of health-related risk factors and
      their response to behavioral interventions.

PMID- 9138623
TI  - Perceptual and coping processes across the menstrual cycle: an investigation in a
      premenstrual syndrome clinic and a community sample.
AB  - Patients from a premenstrual symptoms clinic and asymptomatic controls monitored
      perceived stressors, coping processes, and emotional and physical symptoms daily
      for a complete menstrual cycle. Within-group comparisons revealed that,
      premenstrually, the patients reported encountering a greater number of personal
      competency stressors than they did postmenstrually. Between-group comparisons
      indicated that the patients encountered more stressors and perceived them as more
      stressful during the premenstruum than controls did, whereas postmenstrually the
      groups showed no difference in perceptual style. The patients used situational
      redefinition as a coping process during the premenstrual phase less frequently
      than the controls did. We observed positive relationships for patients between
      daily stressors and emotional and physical symptoms both premenstrually and
      postmenstrually. For controls, the only relationship demonstrated was that
      depression was associated with perceived stressfulness of stressors during the
      premenstrual phase. Results are discussed in the context of psychosocial factors
      (stressors, appraisal, and coping processes) influencing the manifestation of
      premenstrual symptoms.

PMID- 9138624
TI  - Psychosocial influences on central and peripheral vision and reaction time during
      demanding tasks.
AB  - We examined perceptual deficits hypothesized in a model of stress and injury
      relationships. An ophthalmologic perimeter was used to measure peripheral and
      central vision during baseline and demanding task situations for 201
      intercollegiate athletes from 10 sports. We conducted analyses of covariance with
      the stress measures as dependent variables and their appropriate baseline
      measures as covariates. Performance under demanding tasks deteriorated
      significantly on all the perceptual variables. Individuals with high negative
      life events scores experienced greater peripheral narrowing and slower central
      vision reaction time during stress than did those with life events scores that
      were low. Men with low social support had more failures to detect cues, and men
      with high negative life events, low social support, and low coping skills had the
      lowest perceptual sensitivity. Women with high negative life events and low
      coping skills had more failures to detect cues. We discuss the findings in terms
      of how stress responsivity may influence injury risk through changes in
      perception and attention.

PMID- 9138625
TI  - Elevation of plasma beta-endorphin levels of shy elderly in response to novel
      laboratory experiences.
AB  - Heightened psychophysiological reactivity to the novel or unfamiliar is a leading
      characteristic of sky or behaviorally inhibited individuals. To assess one aspect
      of the physiological stress response in shyness, the authors compared the morning
      plasma beta-endorphin levels of 15 extremely sky, healthy elderly individuals
      with beta-endorphin levels of 15 extremely outgoing persons on three pairs of 2
      successive days. The primary finding was that sky participants exhibited
      significantly higher levels of beta-endorphin on the 1st days of each pair of
      days, compared with the 2nd days in the laboratory. No main effect for shyness or
      interaction between shyness and diet on endorphin levels was found. The findings
      are consistent with a peripheral opioid hyperreactivity to novelty in shy elderly
      persons. Shyness may constitute a risk factor for panic disorder in younger
      adults and for nasal allergies and certain cancers in older adults. Experimental
      design and interpretation of future studies of shy individuals' stress responses
      may need to consider novelty versus familiarity of the procedures and setting.

PMID- 9138626
TI  - Anger expression correlates with platelet aggregation.
AB  - Potential relationships between increased platelet aggregability and such
      psychological characteristics as hostility and anger were investigated as part of
      a larger intervention study investigating the potential efficacy of stress
      reduction treatments. Participants performed 6-minute mental arithmetic tests
      under time pressure. Blood was sampled during the first minute of the task and
      whole blood platelet aggregation was measured in an aggregometer, using collagen
      and ADP. To assess anger and hostility, the authors used Spielberger's State
      Trait Anger and Anger Expression scales together with the Cook-Medley Hostility
      Scale. The authors found positive correlations between collagen-induced platelet
      aggregation and outwardly expressed anger, as measured by the Anger Expression
      Scale. The findings suggested that modes of anger expression may be associated
      with increased platelet aggregation. If confirmed by future studies, this finding
      could provide a mechanism for the putative connection between anger/hostility and
      coronary heart disease.

PMID- 9138627
TI  - The developmental toxicity of three antimicrobial agents observed only in
      nonroutine animal studies.

PMID- 9138628
TI  - Weak estrogenic activity from continuous-release pellets.
AB  - In the process of evaluating a proprietary compound for weak estrogenic activity,
      two different types of dosing regimens were used, repeated daily dosing (three
      times/d) and continuous-release pellets. In studies using the proprietary
      compound, rats that were dosed via intraperitoneal injection showed no estrogenic
      responses, while those receiving the test compound via continuous-release pellets
      displayed several estrogenic responses. Because of the conflicting results, the
      control pellets were evaluated for estrogenic activity in the same battery of
      tests using the same number of pellets. In studies using only the control
      pellets, several estrogenic responses were observed including increased uterine
      weight, uterine stromal cell proliferation, estrous conversion, uterine
      progesterone receptor content, and decreased uterine estrogen receptor content.
      Animals receiving no pellet implant showed no estrogenic responses. In addition,
      a methylene chloride/DMSO extract of the control pellets promoted expression of a
      reporter gene controlled by the estrogen receptor and demonstrated competition
      with 17 beta-estradiol for binding to the human estrogen receptor. It is
      concluded that component(s) of the control pellets possess weak estrogenic
      activity.

PMID- 9138629
TI  - Leydig cell hyperplasia and adenoma formation: mechanisms and relevance to
      humans.
AB  - Leydig cell adenomas are observed frequently in studies evaluating the chronic
      toxicity of chemical agents in laboratory animals. Doubts have been raised about
      the relevance of such responses for human risk assessment, but the question of
      relevance has not been evaluated and presented in a comprehensive manner by a
      broad group of experts. This article reports the consensus conclusions from a
      workshop on rodent Leydig cell adenomas and human relevance. Five aspects of
      Leydig cell biology and toxicology were discussed: 1) control of Leydig cell
      proliferation; 2) mechanisms of toxicant-induced Leydig cell hyperplasia and
      tumorigenesis; 3) pathology of Leydig cell adenomas; 4) epidemiology of Leydig
      cell adenomas; and 5) risk assessment for Leydig cell tumorigens. Important
      research needs also were identified. Uncertainty exists about the true incidence
      of Leydig cell adenomas in men, although apparent incidence is rare and
      restricted primarily to white males. Also, surveillance databases for specific
      therapeutic agents as well as nicotine and lactose that have induced Leydig cell
      hyperplasia or adenoma in test species have detected no increased incidence in
      humans. Because uncertainties exist about the true incidence in humans, induction
      of Leydig cell adenomas in test species may be of concern under some conditions.
      Occurrence of Leydig cell hyperplasia alone in test species after lifetime
      exposure to a chemical does not constitute a cause for concern in a risk
      assessment for carcinogenic potential, but early occurrence may indicate a need
      for additional testing. Occurrence of Leydig cell adenomas in test species is of
      potential concern as both a carcinogenic and reproductive effect if the mode of
      induction and potential exposures cannot be ruled out as relevant for humans. The
      workgroup focused on seven hormonal modes of induction of which two, GnRH agonism
      and dopamine agonism, were considered not relevant to humans. Androgen receptor
      antagonism, 5 alpha-reductase inhibition, testosterone biosynthesis inhibition,
      aromatase inhibition, and estrogen agonism were considered to be relevant or
      potentially relevant, but quantitative differences may exist across species, with
      rodents being more sensitive. A margin of exposure (MOE; the ratio of the lowest
      exposure associated with toxicity to the human exposure level) approach should be
      used for compounds causing Leydig cell adenoma by a hormonal mode that is
      relevant to humans. For agents that are positive for mutagenicity, the decision
      regarding a MOE or linear extrapolation approach should be made on a case-by-case
      basis. In the absence of information about mode of induction, it is necessary to
      utilize default assumptions, including linear behavior below the observable
      range. All of the evidence should be weighed in the decision-making process.

PMID- 9138630
TI  - An assessment of boric acid and borax using the IEHR Evaluative Process for
      Assessing Human Developmental and Reproductive Toxicity of Agents. Expert
      Scientific Committee.
AB  - BACKGROUND: Boron is a ubiquitous element widely distributed in nature in the
      form of borates at low concentrations in soils and rocks. Boron is released from
      these minerals by the natural weathering processes in the form of boric acid,
      which is water soluble and biologically available. High levels of boric acid are
      naturally found in sea water. Boric acid and borax are used in the greatest
      quantities and represent the major boron chemical exposures to humans and the
      environment. The principal use of boric acid and borax is in the manufacture of
      various types of glass products that do not result in exposure to the consumer.
      Boric acid and borax are also found in an array of consumer goods including
      fireproofing for fabrics and wood, insecticides, and in many cosmetics and
      personal care products as well. Boron may be an essential element for higher
      animals including humans. HUMAN EXPOSURE: Boric acid and borax are considered to
      be completely absorbed by the oral route of exposure. Absorption through intact
      skin is considered negligible, although absorption can occur through denuded or
      irritated skin. Boron levels in the body do not persist upon cessation of
      exposure. People may be exposed to boron through three primary sources: 1)
      consumption of private, municipal, or commercial (bottled) sources of drinking
      water; 2) dietary consumption of crops and other foodstuffs (including dietary
      supplements for body building); and 3) inhalation of boron compounds during their
      mining, manufacturing, and other industrial processing. While boron has been
      detected in 81.8% of the municipal water systems, it is a minor source of boron
      in most parts of the U.S. The mean boron concentration is reported as 0.2 mg B/L.
      However, residents of California and other western states with boron-rich
      geologic deposits may be regularly exposed to higher levels in drinking water.
      Individuals who drink bottled mineral water may also increase their exposure to
      boron. An EPA health advisory, recommends boron concentrations in drinking water
      not exceed 0.6 mg B/L [0.06 mM B] over a lifetime of exposure. Dietary exposure
      to boron for an adult typically ranges from ranges from 0.25 to 3.1 mg B/d with
      an average of 1.5 mg B/d. The high end of the exposure range, 3.1 mg B/d, was
      selected by the Expert Committee as best estimate of exposure. It should be noted
      that a diet high in fruits, vegetables, grains, legumes, and other food stuffs
      with high boron contents may lead to daily exposures as high as 10 mg B/d from
      diet alone. Some body building supplements contain boron at levels ranging from
      1.5 to 10 mg B, with a median of 4 mg B. Use of the supplements containing the
      median concentration of boron could equal the daily intake an individual receives
      from diet and drinking water combined. Adults in the U.S. at the high end of the
      food exposure range may typically ingest up to 3.5 mg B/d, or a daily dose of
      0.005 mmol B/kg b.wt., through exposure from diet (3.1 mg B/d) and drinking water
      (0.4 mg B/d). Individuals who also use body-building supplements may have a total
      daily boron intake of 7.5 mg B resulting in a daily dose of 0.01 mmol B/kg
      b.wt./d. Occupational exposure to boron is mainly through inhalation of borate
      containing dust during mining and manufacturing processes. Current occupational
      exposures to boron are reported to result in a daily dose of < 0.0001 to 0.2 mmol
      B/kg b.wt./d. Current U.S. OSHA permissible exposure limit (PEL) for sodium
      tetraborates is 10 mg/m3, and the California Occupational Safety and Health
      Administration PEL is 5 mg/m3. An exposure of 5 mg B/m3 translates to
      approximately 0.01 mmol B/kg b.wt./d that, coincidentally, is the same as
      exposure levels associated with combined municipal drinking water, diet, and body
      building supplement consumption. Infants may receive exposures to boric acid when
      it is used as a household insecticide for cockroach control. Exposure from boric
      acid-containing cosmetic and personal care products applie

PMID- 9138631
TI  - Disruption of spermatogenesis in rabbits consuming ethylene glycol monomethyl
      ether.
AB  - Effects of ethylene glycol monomethyl ether (EGME) on spermatogenesis were
      examined using groups of six to seven Dutch rabbits that received 0, 12.5, 25.0,
      37.5, or 50.0 mg of EGME/kg body weight, respectively, in their drinking water
      5d/week. After 12 weeks, animals were euthanized and their testes were removed,
      weighed, and processed to permit germ cell numbers to be quantified.
      Spermatogenesis was depressed by EGME in a dose-dependent manner; numbers of
      round spermatids per Sertoli cell (a measure of spermatogenic efficiency)
      averaged 8.86, 8.87, 6.20, 2.38, and 7.42 for the 0, 12.5, 25.0, 37.5, and 50.0
      mg/kg dosages, respectively. The latter value of 7.42 represents an
      overestimation of sperm production because it is based on only two unexpected
      outlier rabbits. Nearly complete destruction of spermatogenesis occurred in the
      other five animals in this highest dosage group, precluding evaluation by the
      histometric method. Numbers of homogenization-resistant elongated spermatids per
      testis, measurable on all animals, averaged 231, 256, 195, 52, and 67 x 10(6),
      respectively. The correlation between the predicted sperm production, based on
      the elongated spermatids at necropsy, and the number of sperm ejaculated by the
      males during week 12 was 0.92. Thus, EGME impaired rabbit spermatogenesis in a
      dose-dependent manner. Generally, rabbit spermatogenesis was at least 10 times
      more sensitive to EGME than previously reported for rats and mice.

PMID- 9138632
TI  - Reproductive effects of prenatal exposure to 5-bromo-2'-deoxyuridine on male
      rats.
AB  - 5-Bromo-2'-deoxyuridine (BrdU) was administered intraperitoneally to Sprague
      Dawley rats at doses of 12.5, 25, 50, or 100 mg/kg/d on days 9 through 15 of
      gestation, and at 50 or 100 mg/kg/d on days 16 through 20 of gestation. Dams were
      allowed to deliver naturally and the numbers of live and dead pups were recorded.
      Male offspring were allowed to mature and then cohabited with untreated female
      rats for assessment of reproductive performance. Dam body weight gain during
      pregnancy and lactation periods was not reduced by the treatment with BrdU. Dams
      treated with 50 and 100 mg BrdU/kg on days 9 through 15 of gestation had litters
      with decreased survival rates. The male offspring from dams treated with 25, 50,
      and 100 mg BrdU/kg on days 9 through 15 of gestation had reduced body weights
      over the course of the entire study. A dose-related decrease in copulation and
      fertility rates was found in the male offspring of dams treated on days 9 through
      15 of gestation, while no significant decrease in those rates were found in the
      male offspring of dams treated on days 16 through 20 of gestation. Neither
      histopathologic examination of testes nor sperm examination indicated the cause
      of the impaired fertility in the male offspring from dams treated with BrdU on
      days 9 through 15 of gestation. All of the male offspring of dams treated with
      100 mg BrdU/kg on days 9 through 15 of gestation failed to copulate, and some of
      the male offspring of dams treated with 50 mg BrdU/kg on days 9 through 15 of
      gestation did not form copulatory plugs or formed very small plugs. Dilatation of
      the lateral ventricles and cysts in the pars distalis of the pituitary were
      observed in all of the male offspring of dams treated with 100 mg BrdU/kg on days
      9 through 15 of gestation. The impaired fertility of the male offspring of dams
      treated prenatally with BrdU may have resulted from BrdU exposure effects on
      central nervous system action such as loss of libido and from failure to form
      proper copulatory plugs, rather than the direct effects of BrdU on the male
      reproductive organs.

PMID- 9138633
TI  - Histopathologic changes in the testes of rats exposed to dibromoacetic acid.
AB  - The present report details histopathologic changes in the testis and epididymis
      of rats gavaged daily for 2 to 79 d with a by-product of water disinfection,
      dibromoacetic acid (DBAA). On treatment day 2 abnormal retention of Step 19
      spermatids was observed in animals given the highest dosage of 250 mg/kg.
      Additional changes on day 5 included the fusion of mature spermatids and the
      presence of atypical residual bodies (ARB) in the epithelium and lumen of Stage X
      XII seminiferous tubules. By day 9, ARB were seen in most stages of the
      seminiferous epithelial cycle and in the caput epididymidis. On day 16 distorted
      sperm heads were recognized in Step 12, and older spermatids, and luminal
      cytoplasmic debris was found throughout the epididymis. On day 31, there was
      vacuolation of the Sertoli cell cytoplasm, extensive retention of Step 19
      spermatids near the lumen of Stage IX and X tubules, and vesiculation of the
      acrosomes of late spermatids. Marked atrophy of the seminiferous tubules was
      present 6 months after 42 doses of 250 mg/kg. ARB and retention of Step 19
      spermatids were observed after 31 and 79 doses of 50 mg/kg and increased
      retention of Step 19 spermatids was seen in several rats dosed with 10 mg/kg. No
      abnormalities were detected at the dosage of 2 mg/kg. The changes suggest that
      the testicular effects of DBAA are sequelae to structural and/or functional
      changes in the Sertoli cell.

PMID- 9138634
TI  - Metabolism and testicular toxicity of 1,3-dinitrobenzene in the rat: evaluation
      of the stage-synchrony model.
AB  - Because many testicular toxicants cause damage to specific stages of
      spermatogenesis, the present study has investigated the utility of a model in
      which the testis is synchronized to contain only a few closely related
      spermatogenic stages. The susceptibility of different stages to 1,3
      dinitrobenzene (1,3-DNB) toxicity was investigated in rats, the testes of which
      had been stage synchronized by a vitamin A depletion/repletion (VADR) procedure.
      1,3-DNB (25 mg/kg, IP) or vehicle was injected 58, 61, or 78 d after vitamin A
      readministration, and testicular histopathology was evaluated 48 h later. At the
      time of sacrifice, testes in the three groups were synchronized to stages I-VI,
      VII-IX, or X-XIV+I. The data indicated that tubules in all stages of
      spermatogenesis, in both synchronized and unsynchronized animals, demonstrated
      histopathologic changes in response to 1,3-DNB. However, the lesion seen in
      synchronized animals was more severe and less stage specific than that seen in
      weight-matched, unsynchronized animals. This increase in degree of susceptibility
      could be partially explained by differences in toxicokinetics. Stage-synchronized
      testes could provide unique insights into stage-specific cellular and molecular
      events, especially for in vitro studies where the stage enrichment could be
      maximally exploited. However, results obtained from in vivo toxicity studies
      using animals subjected to VADR should be interpreted carefully in light of the
      confounding physiologic/metabolic perturbations potentially induced by the VADR
      procedure.

PMID- 9138635
TI  - Stimulating effects of 4-chlorodiphenyl ether on surgically induced endometriosis
      in the mouse.
AB  - The objectives of this study were to evaluate the effects of repeated injection
      of 4-chlorodiphenyl ether (4-CDE) on the survival and growth of endometriotic
      implants. Endometriosis was surgically induced in adult female B6C3F1 mice (n =
      25) after ovariectomy. Seven days later the animals were randomly divided into
      five groups and treated with vehicle alone (corn oil, control), or 20
      micrograms/kg/d estrone (positive control), or 10, 75, or 150 mg/kg/d 4-CDE in
      vehicle for 28 d. The number and size of the endometriotic cysts were recorded
      and the cysts were then harvested for histology at necropsy 2 d after the last
      treatment. There were significantly more cysts formed (P < 0.05) in the 150
      mg/kg/d 4-CDE group compared to the vehicle-treated control (60 vs. 8%), but not
      compared to the estrone-treated positive control (90 vs. 60%). Hepatic enzymes
      were evaluated to confirm exposure and to further clarify the enzymatic route of
      4-CDE biotransformation by the liver. In conclusion, the repeated exposure to 4
      CDE increased the survival rates of the endometriotic cysts in the ovariectomized
      mouse, which suggests that 4-CDE mimics estrogen effects on endometriotic tissues
      because the endometrial tissues are dependent on estrogenic support for survival.

PMID- 9138636
TI  - Inhibition of ovarian compensatory hypertrophy by the administration of methyl
      parathion in hemicastrated albino rats.
AB  - Methyl parathion, an organophosphorus pesticide that is a potent
      acetylcholinesterase inhibitor in animals, was administered IP in graded doses
      from 2.5 to 5.0 mg/kg body weight to normal hemicastrated virgin rats for 15
      consecutive days. Sham-operated and hemicastrated control groups were treated
      with a similar quantity of olive oil vehicle. The vaginal smears and body weights
      of treated and control groups were recorded daily and rats were sacrificed on the
      16th day. The ovaries, adrenals, liver, kidney, and uterus were removed and
      weighed, and the ovary from each animal was serially sectioned and stained for
      histologic studies. The hemicastrated control group revealed a significant
      increase in ovarian weight with 45% hypertrophy and a significant increase of
      total healthy and atretic follicles when compared with sham-operated control
      rats. Treatment with 2.5 and 3.5 mg methyl parathion revealed no change in the
      ovarian weight with 48 and 42% hypertrophy, respectively, and no change in
      healthy and atretic follicles when compared with hemicastrated oil-treated
      controls. However, treatment with 4.0 and 5.0 mg methyl parathion resulted in a
      significant decrease in ovarian weight gain with 13 and 8% hypertrophy,
      respectively, a significant decrease in the number of healthy follicles, and no
      change in the atretic follicles. The number of estrous cycles and duration of
      each estrous cycle were affected significantly with 3.5, 4.0, and 5.0 mg methyl
      parathion treatment when compared with controls. There were no significant
      changes in adrenal, liver, kidney, or uterine weight in the methyl parathion
      treated groups except a decrease in uterine weight with 5.0 mg treatment when
      compared with oil-treated hemicastrated controls.

PMID- 9138637
TI  - Paracetamol overdose in pregnancy analysis of the outcomes of 300 cases referred
      to the Teratology Information Service.
AB  - A prospective study was carried out to investigate the outcome of pregnancy in
      300 women who had self-administered an overdose of paracetamol, either alone, or
      as part of a combined preparation. Exposure occurred in all trimesters. The most
      striking feature of this study is that the majority of the pregnancies had normal
      outcomes. Over half of the mothers (160 = 53%) required treatment for the
      overdose, and 49 of these had specific antidotes (33 mothers had acetylcysteine
      and 16 mothers had methionine). The rest of the mothers were given nonspecific
      treatments including ipecacuanha (52), gastric lavage (42), and charcoal (16).
      None of the mothers died. There were 219 liveborn infants with no malformations,
      61 of whom had been exposed in the first trimester. Eleven liveborn infants had
      malformations; none was exposed in the first trimester. On other infant exposed
      at 18 weeks had a diaphragmatic hernia; this pregnancy was terminated at 22
      weeks. In none of these 12 infants can the malformations be directly associated
      with paracetamol exposure. There were no apparent differences either in the sex
      ratio or the body weights of term infants. There were seven full-term infants
      with neonatal problems that seem unrelated to paracetamol exposure. Six premature
      infants also had neonatal problems, which were more likely to be related to their
      degree of prematurity rather than paracetamol exposure. There was no obvious
      relationship between the time of exposure and the time of delivery. The overall
      conclusion is that paracetamol overdose per se is not an indication for
      termination of pregnancy.

PMID- 9138638
TI  - Multiple chemical exposures: synergism vs. individual exposure levels.
AB  - Exposure to single chemicals is known to produce congenital malformations in both
      pregnant animals and humans exposed at sufficiently high intensity. However, real
      life involves multiple, simultaneous exposures. Using as a database the 43
      multiple chemical exposure studies located by Nelson (Teratology 49:33-71; 1994)
      where synergism was reported, we explored the degree to which such concerns may
      be realistic from the viewpoint of the current standard developmental toxicity
      safety evaluation process. Focusing on the assessment of the lowest tested dose
      of a given agent participating in synergistic activity as compared to its
      threshold level for eliciting toxicity when administered alone, we found that
      while the availability of adequate data was limited, all cases, with the possible
      exception of one, demonstrated synergistic toxic expression only when at least
      one, and usually both, compounds were used at or above their individual threshold
      for toxicity. These findings suggest that in animals such phenomena of
      synergistic chemical interactions are likely to occur only when at least one and
      more likely both agents are administered at or above their individual threshold
      for toxicity. To the extent animal studies are predictive of human developmental
      hazards due to single chemical exposures, available data do not establish
      multiple chemical exposures as a major human developmental concern.

PMID- 9138639
TI  - Transplacental cisplatin exposure induces persistent fetal mitochondrial and
      genomic DNA damage in patas monkeys.
AB  - A previous attempt to model transplacental cisplatin exposure and genotoxicity
      employed several pregnant Erythrocebus patas monkeys; most of the animals were
      exposed near the end of gestation and cisplatin-DNA adduct analyses included only
      genomic DNA. Here, both genomic and mitochondrial DNA adduct formation have been
      determined in fetuses from two pregnant monkeys exposed at the end of the second
      trimester of gestation. Multiple fetal tissues were obtained after doses of 0.315
      mg cisplatin/kg body weight (5.3 mg/m2 total) on days 101 and 106 of gestation.
      Cesarean sections were performed 24 h after exposure and 27 d after exposure.
      Cisplatin genomic (g)-DNA adducts were observed in fetal adrenal, brain, heart,
      kidney, liver, skin, spleen, and thymus. When placentas from the two animals were
      divided into four concentric regions at increasing distances from the umbilical
      cord, and g-DNA was assayed, cisplatin DNA adduct levels were similar in all four
      regions. Mitochondrial (mt)-DNA adducts were higher than g-DNA adducts in
      maternal liver and fetal liver, brain and kidney, suggesting that the
      mitochondria may constitute a particular target for cisplatin genotoxicity. The
      study demonstrates significant fetal genotoxicity in g-DNA and mt-DNA of patas
      monkeys exposed to cisplatin in utero, suggesting that similarly exposed human
      fetuses may also sustain drug-induced DNA damage.

PMID- 9138640
TI  - [The emotional development of children].
AB  - In the context of pre-school and school medical examinations in the public health
      service in Germany general rating of the cognitive and motor skills of a child is
      often included. In contrast thereto, emotional development and emotional
      situation of children are still a domain of intuition. The present article
      reviews the developmental psychology and psychopathology of emotions. Data of a
      video analysis of non-verbal emotional behaviour during a verbal task are
      presented with respect to shame and associated motor behaviour. In a child
      psychiatric recourse population (n = 2353), the developmental aspect of major
      child psychopathology, is pointed out in the context of the ICD-10 diagnostic
      system.

PMID- 9138641
TI  - [Evaluation of Federal Health Insurance process data as instrument for structural
      and quality analysis of inpatient care].
AB  - Statistically based quality assurance, despite its advantages also has a few
      marked disadvantages. In particular, it is not proven that it promotes measures
      of internal quality assurance. Instead, processing data of the statutory health
      insurance bodies are shown as flexible and easily available data covering a
      defined population and region. Hence, these processing data may be the starting
      point for internal quality management in hospitals. As examples, from an analysis
      of hospitalised cases some questions were derived concerning the structure and
      quality of hospital care. These questions should be answered by common efforts of
      hospitals, health insurance bodies, and public institutions. This may guarantee
      good and efficient inpatient care.

PMID- 9138642
TI  - [A cost of illness study of diabetes mellitus].
AB  - In a cost of illness study on the basis of data of a representative random sample
      of members of a Local Statuary Health Insurance (Allgemeine Ortskrankenkasse,
      AOK) treatment with anti-diabetics and the treatment controls in 1990 were
      recorded. The costs according to the type of diabetes treatment in 1990 were
      determined and compared with the estimated costs for treatment and therapy
      control corresponding to international standards. The random sample corresponds
      to the required standards in health economics of a population-related random
      sample, which is continually observed in the course of at least one year. The
      costs per diabetic patient were checked, as well as the costs which were shared
      by the insured community per 1,000 insured people for the treatment of their
      members affected with diabetes. Among 1,000 insured members there were 49
      diabetes patients (standardised according to the age and sex distribution of the
      former West Germany). Of these 49 patients, 9 were insulin recipients, 25 were
      recipients of oral anti-diabetics, and 15 were diet-treated patients. Total costs
      amounted to DM 16,896/ 1,000 insured/ year. Of this total, DM 12,905 were
      accounted for by drug therapy and DM 3,991 by the therapy control. The estimates
      for a therapy corresponding to international standards in comparison to the
      applied therapy showed that a therapy following the recommendations would be 54%
      more expensive and therefore rise to DM 26,023/1,000 insured/year. A comparison
      of the therapy costs for the various diabetes groups shows that the costs for an
      insulin treated patient was roughly 6 times as high as for a patient treated
      orally and 30 times as high as for a diet-treated patient. However, applied to
      all diabetics in the insured community, a different relationship became apparent,
      depending on the prevalence of the diabetes sub-group. Only twice as much was
      expended for the insulin-treated patients (DM 11,074/1,000 insured/year) than for
      OAD recipients and diet treated patients put together (DM 5,822/1,000
      insured/year). If the therapy corresponded to the minimal requirements of the
      recommendations, then the ratio of the estimated costs for the total of OAD and
      diet-treated patients (DM 10,031/1,000 insured/year) to insulin-treated patients
      (DM 15,992/1,000 insured/year) should be 1:1,5. It is emphasised that the costs
      of diet-treated patients rises relatively higher than those of the other two
      groups, because until now there has been no self control in this group.

PMID- 9138643
TI  - [Incidence of ectromelia deformities in the Magdeburg region].
AB  - Since there is no nationwide system and documentation of congenital malformations
      in Germany, local health authorities were not able to respond to the question of
      an increase in limb reduction defects occurring on the coast of Northern Germany.
      Previously, such an increase had been reported by the media in England in 1994.
      For limb reduction defects, the feasibility and efficiency of the so-called
      "Magdeburg-model" for monitoring congenital malformations is demonstrated. This
      model provides data on reduction defects for analysing regional (Magdeburg versus
      Magdeburg county) and temporal trends, and for classifying reduction defects. The
      data are based on a population of 214.901 births (lifebirths and stillbirths) and
      on the analysis of 64 cases with limb reduction defects over a 15-year period. In
      1992-1994 in Magdeburg and Magdeburg county no increase of limb reduction defects
      and other indicator malformations were found.

PMID- 9138644
TI  - [Ambulatory management during the transformation process--a survey of physicians
      in new German districts].
AB  - The transformation of the health care system in the former GDR is demonstrated
      empirically on the basis of postal surveys conducted in 1990/91 with reference to
      the following spheres: 1. Routine problems. In diagnosis and therapy, the central
      problem was that the equipment required was often either lacking or defective. 2.
      Social perception. Female doctors regarded themselves as more understanding,
      progressive, sensitive, and friendly than their male colleagues. 3. Dynamics of
      transformation. The percentage of doctors with a practice of their own increased
      from 1990 to 1991 from 4.2 to 61.4%. 4. Reasons for starting a private practice.
      For male doctors the motives of greater latitudes in defining working hours and
      work routines as well as long-term expectations of increasing income were
      significantly more important than for female doctors. 5. Initial problems. Three
      aspects proved to be the most significant: too little time for family, work load
      too high, accounting problems. 6. Job satisfaction. In the course of time, the
      greatest increase in satisfaction was found to be related to possibilities of
      advanced professional training and income. A significant trend toward decreasing
      satisfaction was noted for dimensions such as work load, relationship between
      work and leisure, as well as secretarial work and accounting.

PMID- 9138645
TI  - [Approaches to explaining social maldistribution of illnesses and mortality].
AB  - Socially unequal distribution of illness and mortality rates is nothing new.
      Studies dealing with this phenomenon date back to at least the past century.
      Despite this age-old tradition, explanatory patterns in respect of socio
      epidemiology. are few and far between. The following article describes the
      approaches that have been tried to date. Materialistic explanations are the order
      of the day in British socio-epidemiology. It is assumed that low income results
      in increasing everyday problems due to lack of resources, funds being no longer
      sufficient to maintain health. Another series of explanations is based on
      characteristics of working conditions. According to this theory, cardiovascular
      risk is increased by combinations such as high demands/low wages and high
      demands/low level of controlling the work. Characteristic features of job
      activity also exercise a long-term influence on mental flexibility and problem
      solving competence. The characteristic pattern realisations that are considered
      undesirable, occur more frequently in the lower strata of society. Events
      resulting in stress bringing about a change in life, as well as lack of basic
      social support, are also more frequently seen in the lower strata of society. The
      theory of experience of coherence postulates that a more efficient solution of
      problems and less subjective stress are associated with perceiving the
      environment as coherent and manageable. This characteristic, too, is
      sociostructurally not uniformly distributed.

PMID- 9138646
TI  - [Human biomonitoring--studies of arsenic, lead and PCDD/F in inhabitants of a
      contaminated residential area].
AB  - The levels of arsenic in urine, lead in blood, and PCDD/F in blood fat were
      determined in 12 subjects living in a residential area where the soil was
      contaminated by arsenic, lead, PCDD/F and other pollutants. Six residents (group
      I, mean age 56 years) were living on the contaminated site for at least 35 years,
      and had consumed home-grown vegetables and fruits as well as self-produced animal
      products (eggs, meat). Six residents (group II, mean age 47 years) had been
      living on the contaminated site for an average period of 9 years, and had
      consumed only minor amounts of home-grown vegetables and fruits, but no self
      produced animal products. Some of them had skin contact with contaminated soil
      during excavation and garden work. For comparison, blood and urine samples of
      subjects living in the same region but not exposed to soil contaminants were
      investigated for the above mentioned parameters. The reference subjects were
      selected by age and gender in order to form matched pairs with the exposed
      subjects. The levels of arsenic in urine and lead in blood did not differ
      significantly between the residents of the contaminated area and the reference
      subjects. With regard to PCDD/F in blood fat a significantly increased PCDD/F
      body burden was found for the subjects of group I (median: 41.5 pg I-TE/g fat,
      range: 18.0-54.6 pg I-TE/g fat; reference group, median: 20.3 pg I-TE/g fat,
      range: 12.2-30.5 pg I-TE/g fat), whereas the subjects of group II had only a
      moderately, but not significantly increased PCDD/F-body burden (median: 23.4 pg I
      TE/g fat, range 13.1-45.8 pg I-TE/g fat) when compared with the reference group
      (median: 13.9 pg I-TE/g fat, range: 12.1-30.5 pg I-TE/g fat). Increased PCDD/F
      levels in blood fat seemed to be related mainly to the consumption of self
      produced animal products. From the present-day toxicological point of view, none
      of the subjects examined in this study had a critical body burden of PCDD/F.

PMID- 9138647
TI  - [Social medicine in the ecology curriculum--Leipzig experiences with a social
      medicine practicum].
AB  - Apart from only offering lectures, Leipzig university introduced, within the
      scope of the "Ecological course", a newly outlined practical training in the
      field of social medicine. The topics of this practical training were: living with
      handicaps: chronic illness; psychosocial problems. The training consisted of two
      seminars and one attendance at disabled persons' unions and self-help groups. In
      addition to that, extern experts held lectures on the feasibility of
      rehabilitation. Each team, consisting of 3-5 students, was expected to write a
      report on their attendance in order to prove their efforts. Later on, these
      reports suppled the basis for discussion in the second seminar. The high quality
      of these reports clearly shows the students' interest in this kind of training.
      Some especially interested students took an active part in a final scientific
      colloquium, delivering their own lecture reports. Summing up, this teaching
      concept proved truly successful and should be continued.

PMID- 9138648
TI  - [Comment on K. Lohmann, Anke Prohl, E. Schwarz. Multiple chemical sensitivity in
      patients with neurotoxic illnesses].

PMID- 9138649
TI  - Special issue: Band 3 anion transporters in health and disease. Dedicated to Dr.
      Joseph R. Goodman on his 85th birthday.

PMID- 9138650
TI  - Thermomechanical analysis of shape memory devices.
AB  - Shape memory alloys (SMA) are being increasingly used in various industrial
      applications as actuators, connectors, or damping materials. In the medical
      field, superelastic devices such as eyeglass frames, stents or guide catheters
      have come to market in the recent years. The design of SMA devices has usually
      been based on trial and error, since until recently no general simulation model
      was available to assist application engineers. The purpose of this article is to
      describe the computational methodology developed, validated and used for several
      industrial projects at Ecole Polytechnique of Montreal to simulate the
      thermomechanical behavior of shape memory materials. This new approach includes
      three main stages: experimental characterization, construction of a nonlinear
      material law based on dual kriging interpolation and finally, calculation of the
      thermomechanical response of SMA devices. For complex geometry, finite element
      analysis is used, but for simple devices such as springs or electrically
      activated SMA wires, simplified calculation methods are satisfactory. Validation
      results recently obtained will also be presented, and examples of industrial
      applications briefly reviewed.

PMID- 9138651
TI  - Cytotoxicity of synthetic barium hydroxyapatite.
AB  - Barium hydroxyapatite (Ba10(PO4)6(OH)2, Ba-HAp) was synthesized by a wet method
      using Ba(OH)2.8H2O and (NH4)2HPO4 as starting materials. The Ba-HAp obtained had
      a Ba/P atomic ratio of 1.76 and contained CO3 groups. The Ba-HAp was sintered at
      1073 K for 12 hours. The sintered Ba-HAp had a three point bending strength of 29
      MPa and Young's modulus of 27 GPa. Cytotoxicity of the sintered bodies and
      particles was tested using L-cells. The sintered Ba-HAp showed no cytotoxicity,
      and the cells were closely in contact with the surfaces of sintered Ba-HAp.
      Morphological observation of the cell around the Ba-HAp particles also showed no
      cytotoxicity. However, cell growth was inhibited by Ca adsorption on the Ba-HAp
      particles. These results suggested that the Ba-HAp had no cytotoxicity and can be
      applied as a bioactive X-ray opaque material.

PMID- 9138652
TI  - Generation of three-dimensional medical thermograms.
AB  - To visualise non-invasively human organs in their true form and shape has
      intrigued mankind for centuries. Three-dimensional (3D) imaging is one recent
      development that has brought us closer to fulfilling the age-old quest of non
      invasive visualisation so that diagnoses by doctors can be efficiently enhanced.
      Nowadays, 3D CT and MRI images have been very popular. Thermography is an
      important medical imaging technique that displays the temperature distribution on
      the surface of a human organ and it has been proved to be significant in offering
      a unique physiological reflection of pathology that may confirm or enhance the
      anatomic findings of other diagnostic imaging modalities. It is the only imaging
      modality that can evaluate pain whereas plain radiographs, CT and MRI, etc. can
      only depict structural anatomic abnormalities that may not always coincide with
      patients' clinical complaints. It is against this background that 3D thermograms
      have been developed. A set of comprehensive calibration procedures for the 3
      camera system have been designed based on different models for the optical and
      infrared cameras. The accuracy of the results is high enough to produce 3D
      thermograms that can be used to correlate with the 3D images from other medical
      imaging modalities. One important achievement of the system is that the resultant
      3D images are absolutely dimensioned and hence, it is particularly favourable for
      fully autonomous applications with robots. The system can also provide an overall
      picture of both the structural abnormalities and nervous responses of patients.

PMID- 9138653
TI  - Reinforcement of PMMA bone cement with a continuous wire coil--a 3D finite
      element study.
AB  - The changes in the mechanical response of a bone cement reinforcement, comprised
      of a continuous stainless steel coil imbedded within the PMMA bone cement matrix
      surrounding the distal tip of the total hip arthroplasty, was investigated. To
      achieve this, a 3D finite element model depicting two and one half rotations of
      the coil imbedded within the cement at the distal tip was constructed. Ideally,
      the wire coil should reduce the radial, and to a greater extent, the hoop
      stresses developing within the cement and at the cement-stem interface. As a
      means of comparison, a control model of only bone cement was also built. For the
      radial stresses, the control had about 4.5 times the compressive stress of the
      reinforced models (0.039 (+/-0.00065) MPa vs. 0.0087 (+/-0.0012) MPa) at the
      cement-stem interface. The tensile hoop stresses were also 4.5 times higher
      (4.272 (+/-0.0147) MPa and 0.95 (+/-0.0052) MPa) for the control than for the
      reinforced models. This indicates that the wire coil reinforcement is effective
      in reducing the cement mantle's radial and, more importantly, the hoop stresses
      which may lead to the failure of both the cement and the implant as a whole.

PMID- 9138654
TI  - An observation on subsurface defects of ultra high molecular weight polyethylene
      due to rolling contact.
AB  - Ultra high molecular weight polyethylene (UHMWPE) has been used in artificial
      joints for a few decades, and wear of UHMWPE has been one of the main problems.
      Though many other materials have been tested over the years, the best clinical
      results are still achieved with UHMWPE. This makes the study of UHMWPE,
      especially in relation to artificial joints, very important. Frequently, more
      severe wear can be observed in artificial knee joints than in artificial hip
      joints especially when the flaking-like wear occurs. This flaking-like wear can
      lead to significant destruction of the artificial knee joint. Macroscopically,
      artificial knee joints have combinational movements of rolling and sliding in
      order to simulate the motion of the normal knee joint. The components of motion
      are separated to make study easier. Fatigue tests of UHMWPE under the rolling
      contact condition were performed in this study. Three ceramic spheres were rolled
      over the UHMWPE specimen using 37 degrees C distilled water as a lubricant. The
      UHMWPE specimen was observed by the scanning acoustic tomography, microscopy, and
      SEM. Some subsurface defects could be observed by SAT even before experiments.
      Although the apparent wear is not observed on the surface, there was an increase
      in the number of observable subsurface cracks in the UHMWPE specimen. This shows
      that cracks occur under the surface after a 10(7) rolling contact loading, which
      is very close to the cyclic loading and unloading with very little friction
      compared to the sliding contact.

PMID- 9138655
TI  - Fatigue properties and stem subsidence in wire coil reinforced PMMA bone cement:
      a preliminary in vitro study.
AB  - The longevity of the cemented total hip joint replacement depends on the
      integrity of the cement fixation with respect to the interfaces of the metal stem
      and bone, and stress/strain transmission and its distribution. A simple stainless
      steel wire coil was placed around a tapered stem in a simulated cement mantle to
      counteract radial- and hoop-stress and dynamic compression-compression tests were
      performed. The results showed that the wire coil reinforced cement group had a
      higher fatigue (30%) and strength (35%) up to 10(5) loading cycles. The amount of
      stem subsidence during fatigue tests of the wire reinforced group was
      significantly reduced (2.5 times) compared with the control group.

PMID- 9138656
TI  - Parental age in relation to risk of breast cancer.
AB  - Data from a population-based case-control study were analyzed to evaluate risk of
      breast cancer among women according to parental age at the time of subject birth.
      Between 1988-91, breast cancer cases (n = 1,253) were obtained from the statewide
      tumor registry in Wisconsin. Concurrently, population controls (n = 1,121) were
      randomly selected from driver's license lists (if under age 65) and Medicare
      beneficiary files (if 65-74 years). Information regarding parents' ages and
      breast cancer risk factors was obtained by telephone interview. Relative risk
      estimates were very slightly elevated with increasing maternal age, although no
      consistent trend of increasing risk was observed (P for trend = 0.38). No
      association between paternal age and breast cancer risk was observed (P for trend
      = 0.98). Older maternal or paternal age was not associated with risk among any of
      the subgroups examined, except for daughters who had late age at first birth.
      These findings are consistent with the majority of studies that have found little
      or no association between parental age and breast cancer risk.

PMID- 9138657
TI  - Second primary cancers after cancers of the colon and rectum in New South Wales,
      Australia, 1972-1991.
AB  - Data from the New South Wales Central Cancer Registry for the period 1972-1991
      were examined to determine the risk of second primary cancers after an initial
      invasive cancer of the colon (ICD-9 153) or rectum (ICD-9 154). The expected
      numbers of cancers were obtained by assuming that subjects experienced the same
      cancer incidence as prevailed in the corresponding general population and by
      applying sex-, age-, and calendar-specific rates to the appropriate person-years
      at risk. The relative risk (RR) of a second primary cancer was taken to be the
      ratio of observed:expected numbers of second cancers. After colon cancer, there
      was an excess of cancers of the small intestine in both sexes (RRs of 4.5 and
      4.4); prostate (RR = 1.4) and kidney (RR = 1.8) in men; and breast (RR = 1.3),
      body of uterus (RR = 1.9), ovary (RR = 2.8), and thyroid (RR = 2.7) in women.
      Lung cancer occurred less frequently in men than expected (RR = 0.7). After
      rectal cancer, men had increased risks of cancers of the colon (RR = 1.5) and
      prostate (RR = 1.3) and a reduced risk of pancreatic cancer (RR = 0.3). A
      reciprocal relationship of increased risk was seen between cancers of the
      proximal (but not the distal) colon and rectum. Shared luminal risk factors for
      proximal colon cancer and rectal cancer and three syndromes of hereditary
      predisposition to colon cancer seem to be the major contributors to second
      primary cancers in patients with an initial colon cancer. Sources of bias have
      been considered.

PMID- 9138658
TI  - The effect of wheat bran fiber and calcium supplementation on rectal mucosal
      proliferation rates in patients with resected adenomatous colorectal polyps.
AB  - Colorectal cancers continue as the second most common cause of death from cancer
      in the United States. Only a few prospective, randomized clinical trials have
      been performed to evaluate the potential preventive effects of dietary fiber or
      calcium in patients with an increased risk for the development or recurrence of
      colorectal cancer. We designed and conducted a double-blinded, placebo-controlled
      randomized trial involving supplementation of fiber and calcium intake and
      measurements of [3H]thymidine labeling index (LI) percentages in rectal mucosal
      biopsies obtained from patients with resected colorectal adenomas to examine the
      potential mechanisms by which dietary interventions might reduce colorectal
      cancer risk. We performed a randomized, double-blinded, Phase II study, using a
      factorial design to measure the effects of supplemental dietary wheat bran fiber
      (2.0 or 13.5 g/day) and calcium carbonate (250 or 1500 mg/day elemental calcium)
      supplementation on [3H]thymidine LI percentages in rectal mucosal crypts and 24-h
      in vitro outgrowth cultures. Measurements were made at baseline randomization
      (i.e., after a 3-month placebo run-in period using 2.0 g of wheat bran fiber plus
      250 mg of calcium carbonate) and after 3 and 9 months on treatment in 100
      randomized participants who had a history of colon adenoma resection. Neither the
      wheat bran fiber nor the calcium carbonate supplements significantly reduced
      [3H]thymidine LI percentages in rectal mucosal crypts (total or compartmental
      analysis) or 24-h in vitro outgrowth cultures at either 3 or 9 months of daily
      supplementation in the 93 evaluable participants. We conclude that 9 months of
      high-dose wheat bran fiber and calcium carbonate supplementation in study
      participants with a history of recently resected colorectal adenomas does not
      have a significant effect on cellular proliferation rates in rectal mucosal
      biopsies, comparing 3- and 9-month results to baseline results. Ultimately, there
      is great need for the evaluation of these two different nutrient interventions in
      the setting of Phase III studies wherein adenomatous polyp recurrence, rather
      than a rectal mucosal biomarker, serves as the primary end point.

PMID- 9138659
TI  - p53 alterations but no human papillomavirus infection in preinvasive and advanced
      squamous esophageal cancer in Italy.
AB  - Geographic differences in exposure to suspected carcinogens have been identified
      in esophageal carcinogenesis, and both p53 alterations and human papillomavirus
      (HPV) infection have been reported in esophageal squamous carcinoma (ESC) from
      high-risk areas, including China and South Africa. The status of p53 alterations
      and HPV infection in ESC has not been determined in northern Italy, where the
      incidence of ESC is low. Formalin-fixed paraffin-embedded esophageal samples
      containing normal, dysplastic, and carcinomatous tissue from 18 patients were
      examined for p53 protein accumulation with immunohistochemistry, p53 mutation
      (exons 5-8) with PCR-single-strand conformation polymorphism analysis and DNA
      sequencing, and HPV infection with PCR using general primers to amplify the L1
      gene. Accumulation of p53 protein was observed in both precancerous and
      carcinomatous lesions. p53 mutations were rare in dysplastic lesions but were
      detected in 9 of 18 carcinomas, a finding consistent with reports from other
      geographic areas. Examination of the p53 mutation spectrum revealed no hot spot
      mutation. In contrast, HPV was not found in any of these 18 cases. This is
      consistent with the findings from other low ESC risk areas in which HPV infection
      may not play a crucial role in esophageal oncogenesis, whereas the high risk of
      ESC in China and South Africa may be attributed to frequent HPV infection.

PMID- 9138660
TI  - Relationship of serum dehydroepiandrosterone (DHEA), DHEA sulfate, and 5
      androstene-3 beta, 17 beta-diol to risk of breast cancer in postmenopausal women.
AB  - Laboratory evidence suggests a role for dehydroepiandrosterone (DHEA) and its
      metabolite 5-androstene-3 beta, 17 beta-diol (ADIOL) in mammary tumor growth.
      Serum DHEA also has been related to breast cancer in postmenopausal women, but
      the relationship of ADIOL to risk has not been evaluated previously. To assess
      the relationship of serum DHEA, its sulfate (DHEAS), and ADIOL with breast cancer
      risk in postmenopausal women, we conducted a prospective nested case-control
      study using serum from the Columbia, MO Breast Cancer Serum Bank. Cases included
      71 healthy postmenopausal volunteers not taking replacement estrogens when they
      donated blood and who were diagnosed with breast cancer up to 10 years later
      (median, 2.9 years). Two randomly selected controls, who also were postmenopausal
      and not taking estrogens, were matched to each case on exact age, date (+/-1
      year), and time (+/-2 h) of blood collection. Significant (trend P = 0.02)
      gradients of increasing risk of breast cancer were observed for increasing
      concentrations of DHEA and ADIOL, and women whose serum levels of these hormones
      were in the highest quartiles were at a significantly elevated risk compared to
      those in the lowest; their risk ratios were 4.0 [95% confidence interval (CI),
      1.3-11.8) and 3.0 (95% CI, 1.0-8.6), respectively. The relationship of DHEAS to
      breast cancer was less consistent, but women whose serum DHEAS concentration was
      in the highest quartile also exhibited a significantly elevated risk ratio of 2.8
      (95% CI, 1.1-7.4). Results of this prospective study support a role for the
      adrenal androgens, DHEA, DHEAS, and ADIOL, in the etiology of breast cancer.

PMID- 9138661
TI  - Evidence for at least two distinct groups of humoral immune reactions to
      papillomavirus antigens in women with squamous intraepithelial lesions.
AB  - Serological markers of squamous intraepithelial lesions (SILs), the precursors of
      cervical cancer, have not been studied extensively. To screen for antibody
      responses that might be associated with SILs, we measured IgG and/or IgA to nine
      antigens based on papillomaviruses, the infectious cause of SIL and cervical
      cancer, using an ELISA format. Cases were 59 women with low grade SIL (LSIL) and
      38 with high grade SIL (HSIL). Controls were 50 women chosen to minimize the
      possibility that they ever had SILs [individuals who had no history of SIL and
      repeatedly tested negative for cervical human papillomavirus (HPV) DNA],
      frequency age-matched to cases. The data showed that five antibodies had strong
      positive associations with SILs and that one was inversely related to SILs. By
      studying these antibodies in pairs, furthermore, we found that case-control
      differences were enhanced. In particular, the combination of IgG to an epitope in
      the E6 protein of HPV 16 (E6:10) and IgA to HPV 16 virus-like particles (VLPs)
      was detected in 53% of LSILs and 65% of HSILs but only 9% of controls. These same
      responses were both negative in just 6% of LSILs and zero HSILs, compared to 59%
      of controls. Notably, E6:10 IgG and HPV 16 VLP IgA were not correlated with each
      other, and the other antibody responses positively associated with SILs could be
      broken into two groups: those correlated with E610 IgG and those correlated with
      HPV 16 VLP IgA. Overall, the data suggest that several papillomavirus antibodies
      may be strongly related to SILs, and that they can be divided into at least two
      independent groups of humoral immune reactions.

PMID- 9138662
TI  - A polymorphism of the 5 alpha-reductase gene and its association with prostate
      cancer: a case-control analysis.
AB  - Prostate cancer (CaP) is the most commonly diagnosed, nondermatological cancer in
      the United States. The development and progression of CaP is influenced by
      androgens. 5 alpha-Reductase, type II, converts testosterone to
      dihydrotestosterone and is critical to the development of the prostate. A TA
      dinucleotide repeat polymorphism exists in the 3' untranslated region of the 5
      alpha-reductase type II gene. 5 alpha-Reductase alleles with longer TA repeats
      are more common in African-Americans, the group with the highest incidence of
      CaP. It has been hypothesized that the longer TA repeat alleles might be
      associated with increased risk of CaP. We studied this potential association
      within the Physician's Health Study, a predominantly Caucasian cohort study.
      Using PCR we identified the TA genotype in 590 men with CaP and 802 age-matched
      controls. The frequency of each allele in the controls was TA(0), 0.87, TA(9),
      0.13, and TA(18), 0.01. Homozygotes for the longer TA alleles, TA(9) and TA(18),
      were underrepresented among cases with an odds ratio of 0.47 (confidence
      interval, 0.20-1.12), but this was not statistically significant (P = 0.08, two
      tailed). Our analysis does not support the prior hypothesis that longer TA
      alleles confer an increased risk of CaP in a predominantly Caucasian population;
      in fact, longer TA alleles are more prevalent in men without CaP.

PMID- 9138663
TI  - Immunoperoxidase quantitation of 4-aminobiphenyl- and polycyclic aromatic
      hydrocarbon-DNA adducts in exfoliated oral and urothelial cells of smokers and
      nonsmokers.
AB  - Immunoperoxidase methods using two antibodies were developed for detection and
      quantitation of DNA damage in single cells. A monoclonal antibody that recognizes
      4-aminobiphenyl (4-ABP)-DNA adducts was initially tested on liver tissues of
      BALB/c mice treated with 4-ABP, then applied to the detection of adducts in oral
      mucosa and exfoliated urothelial cells of smokers and nonsmokers. Levels of 4-ABP
      DNA in exfoliated urothelial cells were elevated in each of 20 smokers (mean
      relative staining intensity, 517 +/- 137) compared with age-, race-, and sex
      matched nonsmokers (313 +/- 79; P < 0.0005). Significantly higher damage levels
      were also observed in oral mucosa cells of smokers compared with nonsmokers (552
      +/- 157 versus 326 +/- 101; P < 0.0005). A polyclonal antiserum that recognizes
      benzo(a)pyrene and structurally related polycyclic aromatic hydrocarbon (PAH)
      diol epoxide-DNA adducts was also applied to the same study samples after
      validation by staining of 10T1/2 cells treated with (+/-)-trans-anti
      benzo(a)pyrene diol epoxide. Smokers had higher levels of PAH-DNA damage in oral
      mucosa and exfoliated urothelial cells than nonsmokers (oral mucosa cells, 684 +/
      107 versus 370 +/- 83; P < 0.0005; urothelial cells, 689 +/- 72 versus 495 +/-
      57; P < 0.0005). A similar 2-3-fold range in relative staining was found in
      smokers and nonsmokers for both 4-ABP- and PAH-DNA, suggesting the importance of
      individual differences in capacity to metabolize the carcinogens and/or repair
      damaged DNA. Significant correlations were found among the biomarkers in both
      cell types. This noninvasive method, requiring small numbers of cells and with a
      relatively low cost, will be useful for monitoring DNA damage in large-scale
      molecular epidemiology studies.

PMID- 9138664
TI  - Mammography screening and the increase in breast cancer incidence in Hawaii.
AB  - This ecological study investigated the association between mammography
      utilization and breast cancer incidence in Hawaii with the hypothesis that
      geographic areas with high mammography use have higher breast cancer incidence
      than geographic areas with low mammography use. Insurance claims for mammograms
      received during 1992 and 1993 were combined with breast cancer incidence data
      from the Hawaii Tumor Registry and data from the 1990 Census ZIP File. The claims
      data were obtained from four private and three public health plans and covered
      approximately 85% of women 40 years of age and older. Age-specific breast cancer
      incidence rates for the 79 ZIP code areas were regressed on mammography rates and
      selected aggregate demographic variables using multiple linear regression. An
      estimated 42% of women 40 years of age and older had received at least 1
      mammogram during 1992 and 1993, with the highest rate (45%) in women ages 50-64
      years old. Overall, 23% of the variation in age-specific breast cancer incidence
      could be predicted by mammography utilization, 23% by increasing age, and 4% by
      higher education. The relationship between mammography use and breast cancer
      incidence was strongest for women 50-64 years old and for localized disease. The
      magnitude of the association between breast cancer incidence and mammography
      utilization was comparable to the increase in breast cancer rates observed in
      Hawaii during the mid-1980s, supporting the hypothesis that the sharp increase in
      breast cancer incidence was attributable to screening and early detection.
      However, the long-term 1% increase in breast cancer incidence requires alternate
      explanations.

PMID- 9138665
TI  - Cognitive maps beyond the hippocampus.
AB  - We present a conceptual framework for the role of the hippocampus and its
      afferent and efferent structures in rodent navigation. Our proposal is compatible
      with the behavioral, neurophysiological, anatomical, and neuropharmacological
      literature, and suggests a number of practical experiments that could support or
      refute it. We begin with a review of place cells and how the place code for an
      environment might be aligned with sensory cues and updated by self-motion
      information. The existence of place fields in the dark suggests that location
      information is maintained by path integration, which requires an internal
      representation of direction of motion. This leads to a consideration of the
      organization of the rodent head direction system, and thence into a discussion of
      the computational structure and anatomical locus of the path integrator. If the
      place code is used in navigation, there must be a mechanism for selecting an
      action based on this information. We review evidence that the nucleus accumbens
      subserves this function. From there, we move to interactions between the
      hippocampal system and the environment, emphasizing mechanisms for learning novel
      environments and for aligning the various subsystems upon re-entry into familiar
      environments. We conclude with a discussion of the relationship between
      navigation and declarative memory.

PMID- 9138666
TI  - Retarded formation of the hippocampal commissure in embryos from mouse strains
      lacking a corpus callosum.
AB  - A precise description of the timing and route traveled by axons traversing the
      telencephalic midline through the ventral hippocampal commissure (HC) is
      essential for understanding the role it plays in the formation of the corpus
      callosum (CC). A normal baseline of HC development was described in B6D2F2 hybrid
      mice and then compared with two inbred strains of mice displaying callosal
      agenesis, BALB/cWah1 (50% CC defect) and 129/J (70% CC defect), their F2 hybrid
      (C129F2-33% CC defect), and a recombinant inbred strain (RI-1-100% CC defect)
      derived from pairs of C129F2 mice. Embryos weighing from 0.25 g to 0.70 g (E14.5
      E17) were collected and fixed by perfusion. Axon tracts were labeled using
      crystals of the lipophilic dyes DiI and DiA inserted into the hippocampal fimbria
      and cerebral cortex. HC axons in B6D2F2 mice first cross the midline at about
      0.350 g body weight (E14.8) by traveling over the dorsal septum and along the pia
      membrane lining the longitudinal fissure. Earlier crossing was prevented by the
      presence of a deep cleft formed by the longitudinal fissure extending down into
      the septal region. Subsequent axons fasciculated along existing axons, gradually
      building the dorsoventral height of the HC to about 200 microns by 0.600 g. The
      earliest callosal axons from frontal cortex crossed the midline at 0.620 g and
      were clearly seen fasciculating along and between existing hippocampal axons at
      the dorsal surface of the HC as they crossed. In the acallosal strains, HC
      formation was delayed by the continued presence of the cleft deep in the septal
      region. This delay in time of crossing was correlated with later CC defect
      expression. Initial HC crossing occurred at about 0.470 g (E16.25) in BALB mice
      and about 0.520 g (E16.5) in 129 mice. In the RI-1 embryos, first HC crossing was
      estimated at about 0.750 g (E17.5), although several older embryos showed no
      crossing. These results show the importance of the HC for successful CC formation
      and suggest that absent CC arises as a consequence of a developmental defect
      which affects the formation of the hippocampal commissure prior to arrival of CC
      axons at midplane.

PMID- 9138667
TI  - Kappa opioid receptor-like immunoreactivity is present in substance P-containing
      subcortical afferents in guinea pig dentate gyrus.
AB  - We have previously shown that kappa opioid receptor-like immunoreactivity (KT-LI)
      is present in axons and terminals in the granule cell layer and inner molecular
      layer of the guinea pig dentate gyrus. The distribution and ultrastructural
      appearance of processes with KT-LI were similar to those of the substance P (SP)
      containing afferents which arise from the supramammillary region of the
      hypothalamus (SUM) and enter the hippocampal formation through the fimbria
      fornix. The objective of the present study was to determine whether the terminals
      with KT-LI are likely to be SUM afferents. To accomplish this we 1) compared the
      intensity of KT- and SP-immunolabeling in the dentate gyrus ipsilateral and
      contralateral to a unilateral fornix transection and 2) used dual-labeling
      electron microscopy to determine whether terminals with KT-LI colocalize SP-LI in
      the dentate gyrus. Light microscopic examination of the dentate gyrus
      demonstrated that KT-LI and SP-LI were in thin processes with overlapping
      distributions in strata granulosum and moleculare. Following fornix transection,
      both KT-LI and SP-LI were dramatically reduced in these regions of the dentate
      gyrus ipsilateral to the transection, consistent with an SUM origin. By electron
      microscopy, most (71%) terminals with KT-LI also contained detectable SP-LI in
      single-section analysis. Many dual-labeled terminals formed thick asymmetric
      synaptic contacts with large dendritic shafts (2-5 microns) or granule cell
      perikarya, and a smaller proportion contacted dendritic spines; these
      characteristics resembled those of identified SUM afferents in other species. The
      demonstrations that 1) KT-LI colocalizes with SP-LI in a morphologically
      distinctive population of axon terminals and 2) most of the processes with KT-LI
      enter through the fimbria-fornix suggest that kappa opioid receptors are present
      in the SUM projection to the dentate gyrus.

PMID- 9138668
TI  - In vitro electrophysiology of rat subicular bursting neurons.
AB  - Intracellular recordings were used to study the electrophysiological properties
      of rat subicular neurons in a brain slice preparation in vitro. Cells were
      classified as bursting neurons (n = 102) based on the firing pattern induced by
      depolarizing current pulses. The bursting response recorded at resting membrane
      potential (-66.1 +/- 6.2 mV, mean +/- SD n = 94) was made up of a cluster of fast
      action potentials riding on a slow depolarization and was followed by an
      afterhyperpolarization. Tonic firing occurred at a membrane potential of
      approximately -55 mV. A burst also occurred upon termination of a hyperpolarizing
      current pulse. Tetrodotoxin (TTX, 1 microM) blocked the burst and decreased or
      abolished the underlying slow depolarization. These effects were not induced by
      the concomitant application of the Ca2+ channel blockers Co2+ (2 mM) and Cd2+ (1
      mM). Subicular bursting neurons displayed voltage- and time-dependent inward
      rectifications of the membrane during depolarizing and hyperpolarizing current
      pulses. The inward rectification in the depolarizing direction was abolished by
      TTX, while that in the hyperpolarizing direction was blocked by extracellular Cs+
      (3 mM), but not modified by Ba2+ (0.5-1 mM), TTX, or Co2+ and Cd2+.
      Tetraethylammonium (10 mM)-sensitive, outward rectification became apparent in
      the presence of TTX. These results suggest that neurons in the rat subiculum can
      display voltage-dependent bursts of action potentials as well as membrane
      rectification in the depolarizing and hyperpolarizing directions. These results
      also indicate that activation of a voltage-gated Na+ conductance may be
      instrumental in the initiation of bursting activity.

PMID- 9138669
TI  - Model of spatio-temporal propagation of action potentials in the Schaffer
      collateral pathway of the CA1 area of the rat hippocampus.
AB  - There is a sharp contrast between the profuse in vivo axonal arborization of CA3
      pyramidal cells in the CA1 area and the low probability of finding pairs of
      connected CA3-CA1 pyramidal cells in vitro. These anatomical differences
      contribute to a connectivity argument for discrepancies between
      electrophysiological data recorded in vitro and in vivo. In order to investigate
      this issue, we have developed a realistic computer model of the Schaffer
      collateral pathway of the hippocampus and analyzed the spatio-temporal
      distribution of action potentials along this pathway following three different
      types of electrical test stimulus. Direct activation of mossy fibers, CA3
      pyramidal cells and focal stimulation of CA1 stratum radiatum were investigated.
      The parameters of the model were selected from available biological data. Spikes
      in Schaffer collaterals were followed from their onset in the CA3 pyramidal cell
      initial segment to the last order branches of their axonal tree in two types of
      configuration: the whole hippocampus and the slice configuration. The anatomical
      and electropysiological characteristics of the mossy fibre and Schaffer
      collateral pathways were found to impose strong constraints on the spatio
      temporal distribution of action potentials in the CA1 area. Specific projection
      zones are determined by the spatial localization of the emitting CA3 pyramidal
      cells. Their position also defines precise time windows during which some CA1
      projection zones receive a large number of correlated signals. Moreover, the
      variability of the delay at the mossy fibre/CA3 pyramidal cell synapse seems to
      provide the CA1 projection zones with a background level of excitation. Finally,
      we show how the patterns of activation obtained in the whole hippocampus are
      different from those obtained in the slice.

PMID- 9138670
TI  - Regional differences in glial cell modulation of synaptic transmission.
AB  - Metabolic integrity of glial cells in field CA1 of the guinea pig hippocampus is
      critical to maintenance of synaptic transmission (Keyser and Pellmar [1994] Glia
      10:237-243). To determine if this tight glial-neuronal coupling is equally
      important in other brain regions, we compared the effect of fluoroacetate (FAC),
      a glial specific metabolic blocker, on synaptic transmission in field CA1 to
      synaptic transmission in area dentata (DG). FAC was significantly more effective
      in decreasing synaptic potentials in CA1 than in DG. A similar regional disparity
      in the FAC-induced decrease in ATP levels was evident. Isocitrate, a glial
      specific metabolic substrate, prevented the FAC-induced synaptic depression in
      both CA1 and DG. The results suggest that glia of CA1 and dentate respond
      differently to metabolic challenge. Modulation of this glial-neuronal coupling
      could provide a regionally specific mechanism for synaptic plasticity.
      Additionally, site-specific glial-neuronal interactions can impact on a variety
      of physiological and pathophysiological conditions.

PMID- 9138671
TI  - Chronic alcohol consumption does not cause hippocampal neuron loss in humans.
AB  - High alcohol consumption for long periods of time causes significant hippocampal
      neurodegeneration in rodents. A single study using neuronal density measures has
      reported similar findings in humans. The present study aims to substantiate these
      findings in human alcoholics using unbiased stereological techniques. Both
      amnesic (n = 5) and nonamnesic (n = 7) chronic alcoholics were selected and
      compared with nonalcoholic controls (n = 8) and patients with marked memory loss
      and hippocampal neurodegeneration caused by Alzheimer's disease (n = 4).
      Hippocampal volume was significantly reduced in the alcoholics and in patients
      with Alzheimer's disease. However, in alcoholics the volume reduction occurred
      exclusively in the white matter, whereas both the gray and white matter were
      reduced in the patients with Alzheimer's disease. Neuron loss occurred
      exclusively from the CA1 and subiculum subregions of the hippocampus in
      Alzheimer's disease. No neuron loss occurred from any subregion of the
      hippocampus in alcoholics. There were no correlations with age and any of the
      volume or neuron number measures. Hippocampal volume correlated with brain volume
      and with the regional gray and white matter volumes within the hippocampus. In
      addition, hippocampal gray matter volume correlated with the number of CA1
      pyramidal neurons. These results do not support the theory that chronic alcohol
      consumption is neurotoxic to hippocampal pyramidal neurons in humans. Further,
      the present results suggest that changes observed in rodent models of alcoholism
      do not parallel those observed in humans, questioning the validity of such
      models.

PMID- 9138672
TI  - Orphanin FQ inhibits synaptic transmission and long-term potentiation in rat
      hippocampus.
AB  - It is known that opioid peptides acting on opioid receptors can modulate
      hippocampal synaptic functions. Although a novel member of the opioid receptor
      family, ORL1 receptors, that displays high-sequence homology with classical
      opioid receptors is abundant in the hippocampus, little is known regarding its
      role in synaptic function. The present study was designed to investigate whether
      activation of the ORL1 receptor by its natural ligand, orphanin FQ, could
      modulate synaptic transmission and synaptic plasticity in the hippocampus. The
      actions of orphanin FQ in the CA1 and dentate gyrus were examined by field
      potential recordings in response to stimulation of Schaffer collaterals and
      perforant path, respectively. Our results showed that orphanin FQ, but not the
      inactive analog des-Phe1-orphanin FQ, reduced both the slope of the excitatory
      postsynaptic potentials and population spike amplitude. The inhibitory effect of
      orphanin FQ is dose dependent and probably involves a presynaptic mechanism, as
      suggested by the significantly increased paired-pulse facilitation evoked in the
      presence of orphanin FQ. In addition, orphanin FQ was found to inhibit the
      induction of long-term potentiation at the Schaffer collateral-CA1 synapse. These
      results demonstrate that orphanin FQ can function as an inhibitory modulator
      regulating synaptic transmission and synaptic plasticity in the hippocampus,
      suggesting that activation of ORL1 receptors may play an important role in
      synaptic plasticity involved in learning and memory.

PMID- 9138673
TI  - LTP and spatial learning--where to next?
AB  - Hebb suggested, in 1949, that memories could be stored by forming associative
      connections between neurons if the criterion for increasing the connection
      strength between them be that they were active simultaneously. Much attention has
      been devoted towards trying to determine a) if there is a physiological substrate
      of such a rule, and b) if so, whether the phenomenon participates in real-life
      memory formation. The discovery of the electrically induced increase in synaptic
      strength known as long-term potentiation (LTP), in the early 1970s, demonstrated
      that a neural version of the Hebb rule could be observed under laboratory
      conditions in the hippocampus, a structure important for some types of learning.
      However, a quarter of a century later, the evidence linking LTP to learning and
      memory is still contradictory. The purpose of the present article is to review
      and assess the types of approach that have been taken in trying to determine
      whether hippocampal synaptic plasticity participates in memory formation.

PMID- 9138674
TI  - Naloxone-insensitive inhibition of acetylcholine release from parasympathetic
      nerves innervating guinea-pig trachea by the novel opioid, nociceptin.
AB  - The novel peptide, nociceptin and the mu-opioid agonist [D-Ala2, N-Me-Phe4, Gly5
      ol]-enkephalin (DAMGO) produced a concentration-dependent inhibition of
      electrical field stimulation (EFS)-evoked release of acetylcholine (ACh) from
      cholinergic nerves innervating guinea-pig trachea. The non-selective opioid
      receptor antagonist, naloxone, did not antagonize the inhibitory action of
      nociceptin under conditions where the inhibition of ACh release evoked by DAMGO
      was completely reversed. It is suggested that DAMGO and nociceptin can inhibit
      cholinergic, parasympathetic neurotransmission to the airways via the activation
      of classical (naloxone-sensitive) and novel (naloxone-insensitive) opioid
      receptors, respectively.

PMID- 9138675
TI  - Inhibition of the constitutive activity of human 5-HT1A receptors by the inverse
      agonist, spiperone but not the neutral antagonist, WAY 100,635.
AB  - At recombinant human 5-hydroxytryptamine (5-HT)5-HT1A receptors expressed in
      Chinese hamster ovary cells (CHO-5-HT1A), 5-carboxamidotryptamine (5-CT), acted
      as a full agonist (relative to 5-HT = 100%) for stimulation of receptor-mediated
      [35S]-GTP gamma S (guanylyl 5'-[gamma-thio]-tryphosphate) binding. In contrast,
      spiperone inhibited basal [35S]-GTP gamma S binding by 30.2% (IC50 = 55.5 nM) in
      CHO-5-HT1A membranes but not in control untransfected membranes. The antagonist,
      N-[2-[4-(2-methoxyphenyl) -1-piperazinyl]ethyl]-N-(2-pyridinyl)-cyclohexane
      carboxamide (WAY 100,635), blocked both 5-CT-induced stimulation and spiperone
      induced inhibition of [35S]-GTP gamma S binding without itself modifying [35S]
      GTP gamma S binding. It is concluded that, in this heterologous expression
      system, 5-HT1A receptors display 'constitutive' activation of G-proteins and that
      spiperone displays inverse agonist activity whereas WAY 100,635 acts as a
      'neutral' antagonist at this site.

PMID- 9138676
TI  - Furosemide interactions with brain GABAA receptors.
AB  - 1. The loop diuretic furosemide is known to antagonize the function of gamma
      aminobutyric acid type A (GABAA) receptors. The purpose of the present study was
      to examine the direct interaction of furosemide with the GABAA receptors by
      autoradiography and ligand binding studies with native rat and human receptors
      and with recombinant receptors composed of rat subunits. 2. Autoradiography with
      [35S]-t-butylbicyclophosphorothionate ([35S]-TBPS) as a ligand indicated that
      furosemide (0.1-1 mM) reversed the 5 microM GABA-induced inhibition of binding
      only in the cerebellar granule cell layer of rat brain sections. In all other
      regions studied, notably also in the hippocampal and thalamic areas, furosemide
      failed to antagonize GABA. Furosemide 1 mM decreased [35S]-TBPS binding only in a
      limited number of brain regions, but facilitation of the GABA-inhibition of the
      binding was much more widespread. 3. In well-washed rat cerebellar, but not
      cerebrocortical, membranes, furosemide enhanced the [35S]-TBPS binding over basal
      level in the absence of added GABA. The GABAA antagonist, SR 95531, and the
      convulsant, Ro 5-4864, blocked this furosemide-induced increase. Both
      interactions with the furosemide enhancement are likely to be allosteric, since
      furosemide affected the binding of [3H]-SR 95531 and [3H]-Ro 5-4864 identically
      in the cerebellar and cerebrocortical membranes. Maximal GABA-antagonism induced
      by furosemide in cerebellar membranes was further increased by SR 95531 but not
      by Ro 5-4864, indicating additive antagonism only for SR 95531. In human
      cerebellar receptors, only GABA antagonism by furosemide, but not the enhancement
      without added GABA, was observed. 4. In recombinant GABAA receptors, furosemide
      antagonism of GABA-inhibition of [35S]-TBPS binding depended only on the presence
      of alpha 6 and beta 2/3 subunits, irrespective of the presence or absence of
      gamma 2 or delta subunits. 5. In alpha 6 beta 3 gamma 2 receptors, clozapine
      reversed the enhancement of [35S]-TBPS binding by furosemide in the absence of
      GABA. However, it failed to affect the GABA-antagonism of furosemide, suggesting
      that the enhancement of basal binding and the GABA antagonism might represent two
      different allosteric actions of furosemide. 6. In conclusion, the present results
      indicate that furosemide is a subtype-selective GABAA antagonist with a mode of
      action not shared by several other antagonists, which makes furosemide a unique
      compound for development of potential GABAA receptor subtype-specific and 
      selective ligands.

PMID- 9138677
TI  - Subunit-dependent interaction of the general anaesthetic etomidate with the gamma
      aminobutyric acid type A receptor.
AB  - 1. The GABA modulating and GABA-mimetic actions of the general anaesthetic
      etomidate were examined in voltage-clamp recordings performed on Xenopus laevis
      oocytes induced, by cRNA injection, to express human recombinant gamma
      aminobutyric acidA (GABAA) receptor subunits. 2. Currents mediated by recombinant
      receptors with the ternary subunit composition alpha x beta y gamma 2L (where x =
      1,2,3 or 6 and y = 1 or 2), in response to GABA applied at the appropriate EC10,
      were enhanced by etomidate in a manner that was dependent upon the identity of
      both the alpha and beta subunit isoforms. 3. For the beta 2-subunit containing
      receptors tested, the EC50 for the potentiation of GABA-evoked currents by
      etomidate (range 0.6 to 1.2 microM) was little affected by the nature of the
      alpha subunit present within the hetero-oligomeric complex. However, replacement
      of the beta 2 by the beta 1 subunit produced a 9-12 fold increase in the
      etomidate EC50 (6 to 11 microM) for all alpha-isoforms tested. 4. For alpha 1,
      alpha 2 and alpha 6, but not alpha 3-subunit containing receptors, the maximal
      potentiation of GABA-evoked currents by etomidate was greater for beta 2- than
      for beta 1-subunit containing receptors. This was most clearly exemplified by
      receptors composed of alpha 6 beta 1 gamma 2L compared to alpha 6 beta 2 gamma 2L
      subunits, where a maximally effective concentration of etomidate potentiated
      currents evoked by GABA at EC10 to 28 +/- 2% and 169 +/- 4% of the maximal GABA
      response, respectively. 5. For alpha 1 subunit-containing receptors, the potency
      and maximal potentiating effect of either pentobarbitone or propofol was
      essentially unaffected by the beta subunit isoform contained within the receptor
      complex. The potency of the anaesthetic neurosteroid 5 alpha-pregnan-3 alpha-ol
      20-one was marginally higher for beta 1 rather than the beta 2 subunit-containing
      receptor, although its maximal effect was similar at the two receptor isoforms.
      6. The GABA-mimetic action of etomidate was supported by beta 2- but not beta 1
      subunit containing receptors, whereas that of pentobarbitone or propofol was
      evident with either beta isoform. For beta 2-subunit containing receptors, both
      the agonist EC50 and the maximal current produced by etomidate were additionally
      influenced by the alpha isoform. 7. It is concluded that the subtype of beta
      subunit influences the potency with which etomidate potentiates GABA-evoked
      currents and that the beta isoform is a crucial determinant of the GABA-mimetic
      activity of this compound. The nature of the alpha-subunit also impacts upon the
      maximal potentiation and activation that the compound may elicit. Such pronounced
      influences may aid the identification of the site that recognises etomidate. More
      generally, these results provide a clear example of structural specificity in
      anaesthetic action.

PMID- 9138678
TI  - Evidence that mechanisms dependent and independent of nitric oxide mediate
      endothelium-dependent relaxation to bradykinin in human small resistance-like
      coronary arteries.
AB  - 1. The effects of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine
      (L-NOARG), the NO scavenger, oxyhaemoglobin (HbO) and high extracellular K+ upon
      endothelium-dependent relaxation to bradykinin were investigated in human
      isolated small coronary arteries. 2. Endothelium-dependent relaxations to
      bradykinin were compared in vessels contracted to approximately 50% of their
      maximum contraction to 124 mM KCl Krebs solution, regardless of treatments, with
      the thromboxane A2 mimetic, U46619 and acetylcholine. All relaxations were
      expressed as percentage reversal of the initial level of active force. 3. L-NOARG
      (100 microM) caused a small but significant, 12% (P < 0.01), decrease in the
      maximum relaxation (Rmax: 91.5 +/- 5.4%) to bradykinin but did not significantly
      affect the sensitivity (pEC50: 8.08 +/- 0.17). Increasing the concentration of L
      NOARG to 300 microM had no further effect on the pEC50 or Rmax to bradykinin. HbO
      (20 microM) and a combination of HbO (20 microM) and L-NOARG (100 microM) reduced
      Rmax to bradykinin by 58% (P < 0.05) and 54% (P < 0.05), respectively. HbO (20
      microM) and L-NOARG (100 microM, combined but not HbO (20 microM) alone, caused a
      significant 11 fold (P < 0.05) decrease in sensitivity to bradykinin. HbO (20
      microM) decreased the sensitivity to the endothelium-independent NO donor, S
      nitroso-N-acetylpenicillamine (SNAP), approximately 17 fold (P < 0.05). 4.
      Raising the extracellular concentration of K+ isotonically to 30 mM, reduced the
      Rmax to bradykinin from 96.6 +/- 3.1% to 43.9 +/- 10.1% (P < 0.01) with no
      significant change in sensitivity. A combination of HbO, L-NOARG and high K+ (30
      mM) abolished the response to bradykinin. High K+ did not change either the
      sensitivity or maximum relaxation to SNAP. 5. In conclusion, L-NOARG does not
      completely inhibit endothelial cell NO synthesis in human isolated small coronary
      arteries. By comparison, HbO appeared to block all the effects of NO in this
      tissue and revealed that most of the relaxation to bradykinin was due to NO. The
      non-NO -dependent relaxation to bradykinin in the human isolated small coronary
      arteries appeared to be mediated by a K(+)-sensitive vasodilator mechanism,
      possibly endothelium-derived hyperpolarizing factor (EDHF).

PMID- 9138679
TI  - Involvement of adrenoceptors in the ovarian vascular pedicle in the regulation of
      counter current transfer of steroid hormones to the arterial blood supplying the
      oviduct and uterus of pigs.
AB  - 1. On Day 10 of the oestrous cycle in pigs, after laparotomy noradrenaline (NA),
      methoxamine (alpha 1-adrenomimetic, M), Prazosin (alpha 1-adrenolytic, Pr) in
      total doses of 4 mumol, and saline were infused (10 min) into the superficial
      layer of mesovarium on both sides of the ovarian pedicle vasculature, close to
      the ovary. 2. Blood flow in the ovarian artery, heart rate and progesterone (P4)
      and androstenedione (A4) secretion from the ovary and their concentrations in the
      ovarian venous effluent, as well as the concentrations of P4 and A4 in the blood
      supplying the oviduct and the uterus, were determined. 3. A significant increase
      of P4 and A4 secretion after NA and M infusion and increased concentrations of P4
      and A4 in the ovarian venous effluent were found, but these changes did not
      influence the counter current transfer of hormones from the venous effluent into
      arterial blood supplying the oviduct and the uterus. 4. Infusion of Pr caused a
      significant decrease of P4 and A4 secretion and their concentrations in the
      ovarian venous effluent and significantly increased A4 concentration in the blood
      supplying the oviduct and uterus. 5. The results indicate that stimulation of
      alpha 1-adrenoceptors in the area of ovarian vasculature did not influence,
      whereas block of alpha 1-adrenoceptors affected, the local concentration of
      steroid hormones in the blood supplying the oviduct and the part of the uterus
      proximal to the ovary, despite the changes in the concentrations of steroid
      hormones in the ovarian effluent.

PMID- 9138680
TI  - Beta-adrenoceptor mediated facilitation of noradrenaline and adenosine 5'
      triphosphate release from sympathetic nerves supplying the rat tail artery.
AB  - 1. The effects of prejunctional beta-adrenoceptor activation on electrically
      evoked noradrenaline (NA) and adenosine 5'-triphosphate (ATP) were studied by use
      of continuous amperometry and conventional intracellular recording techniques.
      Excitatory junction potentials (e.j.ps) were used as a measure of ATP release,
      and NA-induced slow depolarizations and oxidation currents as measures of NA
      release, from postganglionic sympathetic nerves innervating the rat tail artery
      in vitro. 2. Isoprenaline (0.1 microM) increased the amplitude of e.j.ps, slow
      depolarizations and oxidation currents evoked by short trains of stimuli at 1 to
      4 Hz. The facilitatory effect of isoprenaline on e.j.ps and oxidation currents
      was most pronounced on responses evoked by the first stimulus in a train. 3.
      Isoprenaline (0.1 microM) did not detectably alter the amplitude-frequency
      distribution of spontaneous e.j.ps. 4. The facilitatory effect of isoprenaline on
      e.j.ps, slow depolarizations and oxidation currents was abolished by the beta
      adrenoceptor antagonist, propranolol (0.1 microM). Propranolol alone had no
      effect on e.j.ps, slow depolarizations or oxidation currents. 5. Thus, activation
      of prejunctional beta-adrenoceptors increases the release of both NA and ATP from
      postganglionic sympathetic nerves. The findings are consistent with the
      hypothesis that NA and ATP are released from the same population of nerve
      terminals and presumably from the same vesicles.

PMID- 9138681
TI  - Effects of extracellular nucleotides on single cells and populations of human
      osteoblasts: contribution of cell heterogeneity to relative potencies.
AB  - 1. Human osteoblasts responded to the application of extracellular nucleotides,
      acting at P2-receptors, with increases in cytosolic free calcium concentration
      ([Ca2+]i). 2. In populations of human osteoblasts, adenosine 5'-diphosphate (ADP)
      evoked a rise in [Ca2+]i with less than 40% of the amplitude of that induced by
      adenosine 5'-triphosphate (ATP). 3. ATP and uridine 5'-triphosphate (UTP) were
      applied to single human osteoblasts and induced [Ca2+]i rises of comparable
      amplitude in every cell tested. 4. However, from the results of single cell
      studies with ADP (and 2-methylthioATP (2-meSATP)) two groups of cells were
      delineated; one group responded to ADP (or 2-meSATP) with a rise in [Ca2+]i
      indistinguishable from that evoked by ATP; whereas the second group failed
      completely to respond to ADP (or 2-meSATP). 5. Therefore heterogeneity of
      receptor expression exists within this population of human osteoblasts. The
      limited distribution of the ADP-responsive receptor underlies the small response
      to ADP, compared with ATP, recorded in populations of human osteoblasts. This
      heterogeneity may reflect differences in the differentiation status of individual
      cells.

PMID- 9138682
TI  - The effects of spiradoline (U-62066E), a kappa-opioid receptor agonist, on
      neuroendocrine function in man.
AB  - 1. Opioid drugs act on specific receptors which are principally classified into
      mu, delta and kappa subtypes. Spiradoline (U-62066E) is a kappa-selective agent
      which has been shown to possess potent anti-nociceptive effects but does not show
      cross tolerance with morphine. 2. We have assessed the neuroendocrine effects of
      spiradoline in healthy volunteers with two doses (1.6 and 4.0 micrograms kg-1,
      i.m.) of the compound. Six male non-smokers aged 19-27 years were studied by use
      of a randomized, double-blind three-limb placebo-controlled cross-over design.
      Blood was taken from an in-dwelling venous cannula basally and at 15 min
      intervals for 2 h for determination of serum cortisol, prolactin, growth hormone
      (GH) and catecholamines. 3. Psychological function was assessed by the Stanford
      Sleepiness Scale (SSS) and the Addiction Research Centre Inventory (ARCI)
      administered before the medication and at 35 min, 1 h 25 min and 2 h afterwards.
      Cardiovascular variables were recorded at 10 min intervals. Results were analysed
      by analysis of variance. 4. Spiradoline showed a significant (P < 0.05) dose
      dependent increase in free water clearance, as predicted for a kappa-opioid
      agonist. It also caused a dose-dependent stimulation of prolactin, (increment
      over baseline for higher dose 214%), GH (433%) and cortisol (215%) release (P <
      0.05). There were no significant drug-related changes in plasma catecholamines,
      blood pressure, pulse or psychological variables. 5. We have therefore confirmed
      that kappa-opioids increase free-water clearance and may participate in the
      stimulation of prolactin and GH release. In contrast to mu and delta-opioid
      agonists, this novel kappa-agonist stimulates cortisol release in man.

PMID- 9138683
TI  - Renal effects of intracerebroventricularly injected tachykinins in the conscious
      saline-loaded rat: receptor characterization.
AB  - 1. The effects of intracerebroventricularly (i.c.v.) injected substance P (SP),
      neurokinin A (NKA) and [MePhe7]neurokinin B (NKB) were investigated on renal
      excretion of water, sodium and potassium in the conscious saline-loaded rat. The
      central effects of [MePhe7]NKB were characterized with selective tachykinin
      antagonists for NK1 (RP 67580), NK2 (SR 48968) and NK3 (R 820) receptors. 2.
      Whereas SP or NKA (65 or 650 pmol) failed to modify the renal responses,
      [MePhe7]NKB (65-6500 pmol) produced dose-dependent and long-lasting (30-45 min)
      decreases in renal excretion of water (maximal reduction at 65 pmol: from 66.14
      +/- 7.62 to 21.07 +/- 3.79 microliters min-1), sodium (maximal reduction at 65
      pmol: from 10.19 +/- 2.0 to 1.75 +/- 0.48 mumol min-1) and potassium (maximal
      reduction at 65 pmol: from 4.31 +/- 1.38 to 0.71 +/- 0.27 mumol min-1). While 650
      pmol [MePhe7]NKB elevated urinary osmolality, neither 65 pmol nor 6.5 nmol
      [MePhe7]NKB altered this parameter. 3. Both the antidiuresis and antinatriuresis
      induced by [MePhe7]NKB (65 pmol) were significantly blocked by the prior i.c.v.
      injection of R 820 (1.3 nmol, 5 min earlier), although the potassium excretion
      was only partially reduced. However, R 820 did not affect the antidiuresis and
      antinatriuresis elicited by endothelin-1 (1 pmol, i.c.v.). On its own, R 820
      decreased renal potassium excretion with no effect on urinary osmolality and
      renal excretion of water and sodium. The i.c.v. co-injection of RP 67580 and SR
      48968 (6.5 nmol each, 5 min earlier) failed to modify the renal responses to
      [MePhe7]NKB in a similar study. 4. The central effects of [MePhe7]NKB (65 pmol)
      on renal excretion were blocked by the prior i.v. administration of a linear
      peptide vasopressin V2 receptor antagonist (50 micrograms kg-1, 5 min earlier).
      5. These results suggest that the central NK3 receptor, probably located in the
      hypothalamus, is implicated in the renal control of water and electrolyte
      homeostasis through the release of vasopressin in the conscious saline-loaded
      rat.

PMID- 9138684
TI  - Effect of non-toxic mercury, zinc or cadmium pretreatment on the capacity of
      human monocytes to undergo lipopolysaccharide-induced activation.
AB  - 1. Metal salts can inhibit cell activity through direct toxicity to critical
      cellular molecules and structures. On the other hand, they can also change cell
      behaviour by inducing specific genes (including genes encoding members of the
      metallothionein [MT] gene family). Therefore, transition metals may affect cell
      functions either by acting as a toxin, or by transmitting or influencing signals
      controlling gene expression. 2. To explore the latter possibility, we measured
      the ability of low, non-toxic metal pretreatment to alter immune cell behaviour.
      We previously found that pretreatment of human monocytes with zinc induces
      metallothionein gene expression and alters their capacity to undergo a bacterial
      lipopolysaccharide-induced respiratory burst. We showed here that cadmium and
      mercury salts, at concentrations that exert no discernible toxicity, inhibit
      activation of human monocytic leukemia (THP-1) cells. CdCl2 1 microM, ZnCl2 20-40
      microM or HgCl2 2 microM pretreatment for 20 h induced MT-2 mRNA and total MT
      protein accumulation and had no effect on proliferation potential or metabolic
      activity, but significantly inhibited the ability of subsequent
      lipopolysaccharide treatment to induce the oxidative burst, increased adhesion to
      plastic, and MT-2 and interleukin-1 beta (IL-1 beta) mRNA accumulation. 3. The
      phenomenon of metal-induced suppression of monocyte activation, at metal
      concentrations that have no effect on cell viability, has important implications
      for assessment of acceptable levels of human exposure to cadmium, zinc and
      mercury.

PMID- 9138685
TI  - Stimulation by extracellular ATP and UTP of the stress-activated protein kinase
      cascade in rat renal mesangial cells.
AB  - 1. Extracellular adenosine 5'-triphosphate (ATP) and uridine 5'-triphosphate
      (UTP) have been shown to activate a nucleotide receptor (P2U receptor) in rat
      mesangial cells that mediates phosphoinositide and phosphatidylcholine hydrolysis
      by phospholipases C and D, respectively. This is followed by an increased
      activity of the mitogen-activated protein kinase cascade and cell proliferation.
      Here we show that ATP and UTP potently stimulate the stress-activated protein
      kinase pathway and phosphorylation of the transcription factor c-Jun. 2. Both
      nucleotides stimulated a rapid (within 5 min) and concentration-dependent
      activation of stress-activated protein kinases as measured by the phosphorylation
      of c-Jun in a solid phase kinase assay. 3. When added at 100 microM the rank
      order of potency of a series of nucleotide analogues for stimulation of c-Jun
      phosphorylation was UTP > ATP = UDP = ATP gamma S > 2-methylthio-ATP > beta gamma
      imido-ATP = ADP > AMP = UMP = adenosine = uridine. Activation of stress-activated
      protein kinase activity by ATP and UTP was dose-dependently attenuated by
      suramin. 4. Down-regulation of protein kinase C-alpha, -delta and -epsilon
      isoenzymes by 24 h treatment of the cells with 12-O-tetradecanoylphorbol 13
      acetate did not inhibit ATP- and UTP-induced activation of c-Jun phosphorylation.
      Furthermore, the specific protein kinase C inhibitors, CGP 41251 and Ro 31-8220,
      did not inhibit nucleotide-stimulated c-Jun phosphorylation, suggesting that
      protein kinase C is not involved in ATP- and UTP-triggered stress-activated
      protein kinase activation. 5. Pretreatment of the cells with pertussis toxin or
      the tyrosine kinase inhibitor, genistein, strongly attenuated ATP- and UTP
      induced c-Jun phosphorylation. Furthermore, N-acetyl-cysteine completely blocked
      the activation of stress-activated protein kinase in response to extracellular
      nucleotide stimulation. 6. In summary, these results suggest that ATP and UTP
      trigger the activation of the stress-activated protein kinase module in mesangial
      cells by a pathway independent of protein kinase C but requiring a pertussis
      toxin-sensitive G-protein and tyrosine kinase activation.

PMID- 9138686
TI  - Inhibitory action of niflumic acid on noradrenaline- and 5-hydroxytryptamine
      induced pressor responses in the isolated mesenteric vascular bed of the rat.
AB  - 1. The effects of niflumic acid, an inhibitor of calcium-activated chloride
      currents, were compared with the actions of the calcium channel blocker
      nifedipine on noradrenaline- and 5-hydroxytryptamine (5-HT)-induced pressor
      responses of the rat perfused isolated mesenteric vascular bed. 2. Bolus
      injections of noradrenaline (1 and 10 nmol) increased the perfusion pressure in a
      dose-dependent manner. Nifedipine (1 microM) inhibited the increase in pressure
      produced by 1 nmol noradrenaline by 31 +/- 5%. Niflumic acid (10 and 30 microM)
      also inhibited the noradrenaline-induced increase in perfusion pressure and 30
      microM niflumic acid reduced the pressor response to 1 nmol noradrenaline by 34
      +/- 6%. 3. The increases in perfusion elicited by 5-HT (0.3 and 3 nmol) were
      reduced by niflumic acid (10 and 30 microM) in a concentration-dependent manner
      and 30 microM niflumic acid inhibited responses to 0.3 and 3 nmol 5-HT by,
      respectively, 49 +/- 8% and 50 +/- 7%. Nifedipine (1 microM) decreased the
      pressor response to 3 nmol 5-HT by 44 +/- 9%. 4. In the presence of a combination
      of 30 microM niflumic acid and 1 microM nifedipine the inhibition of the pressor
      effects of noradrenaline (10 nmol) and 5-HT (3 nmol) was not significantly
      greater than with niflumic acid (30 microM) alone. Thus the effects of niflumic
      acid and nifedipine were not additive. 5. In Ca-free conditions the transient
      contractions induced by 5-HT (3 nmol) were not reduced by 30 microM niflumic
      acid, suggesting that this agent does not inhibit calcium release from the
      intracellular store or the binding of 5-HT to its receptor. 6. Niflumic acid 30
      microM did not inhibit the pressor responses induced by KCl (20 and 60 mumol)
      which were markedly reduced by 1 microM nifedipine. In addition, 1 microM
      levcromakalim decreased pressor responses produced by 20 mumol KCl. These data
      suggest that niflumic acid does not block directly calcium channels or activate
      potassium channels. 7. It is concluded that niflumic acid selectively reduces a
      component of noradrenaline- and 5-HT-induced pressor responses by inhibiting a
      mechanism which leads to the opening of voltage-gated calcium channels. Our data
      suggest that the Ca(2+)-activated chloride conductance may play a pivotal role in
      the activation of voltage-gated calcium channels in agonist-induced constriction
      of resistance blood vessels.

PMID- 9138687
TI  - Pharmacological characterization of an alpha 1A-adrenoceptor mediating
      contractile responses to noradrenaline in isolated caudal artery of rat.
AB  - 1. The alpha 1-adrenoceptor population mediating contraction of caudal artery of
      rat has been characterized by using quantitative receptor pharmacology. 2.
      Cumulative concentration-effect (E/[A]) curves to noradrenaline (NA) yielded a
      p[A]50 of 5.56 +/- 0.05 (n = 16). Prazosin caused concentration-dependent,
      parallel, dextral shifts of E/[A] curves to NA yielding a pKb of 8.9 (Schild
      regression slope = 1.0). RS-17053 (N-[2-(2-cyclopropyl methoxy phenoxy) ethyl]-5
      chloro-alpha, alpha-dimethyl-1H-indole- 3-ethanamine hydrochloride; 10-100 nM), a
      selective alpha 1 A-adrenoceptor antagonist, produced non-parallel, biphasic,
      dextral shifts of E/[A] curves to NA, suggesting the involvement of more than one
      alpha 1-adrenoceptor subtype. Analysis of the high affinity component yielded an
      apparent pA2 value of 9.2 +/- 0.3. 3. A-61603, a selective agonist at alpha 1A
      adrenoceptors behaved as a full agonist relative to NA and yielded monophasic
      E/[A] curves with a p[A50] of 7.59 +/- 0.04 (n = 15). Pretreatment of tissues
      with chloroethylclonidine (CEC; 100 microM for 20 min, followed by 40 min
      washout), which preferentially alkylates alpha 1B- and alpha 1D-adrenoceptors,
      did not alter E/[A] curves to A-61603. Prazosin (3-300 nM) caused concentration
      dependent, parallel, dextral shifts of E/[A] curves to A-61603 yielding a pA2
      estimate of 9.2 +/- 0.2. 4. Experiments with alpha 1-adrenoceptor antagonists of
      varying subtype selectivities (RS-17053, SNAP 5089, tamsulosin, 5-methylurapidil,
      BMY 7378, HV 723 and REC 15/2739) revealed parallel dextral shifts of E/[A]
      curves to A-61603. Schild regression analyses yielded pA2 estimates of 9.2, 9.3,
      11.2, 9.0, 6.3, 8.7 and 10.0 for RS-17053, SNAP 5089, tamsulosin, 5
      methylurapidil, BMY 7378, HV 723 and REC 15/2739, respectively, although
      deviations from unit slope (possibly reflecting a secondary involvement of
      another alpha 1-adrenoceptor) hindered estimations of pKb for some antagonists.
      The antagonist affinity profile obtained reflects best that described for the
      alpha 1A-adrenoceptor. 5. In conclusion, caudal artery of rat contracts in
      response to NA via activation of at least two alpha 1-adrenoceptor subtypes. One
      of these subtypes displays the pharmacology of the alpha 1A-adrenoceptor, while
      the other remains to be defined. Use of the novel selective agonist, A-61603,
      allows for limited pharmacological isolation of the alpha 1A-adrenoceptor
      permitting characterization of the properties of selective antagonists.

PMID- 9138688
TI  - Inhibition of [3H]-U69593 binding and the cardiac effects of U50, 488H by calcium
      channel blockers in the rat heart.
AB  - 1. The calcium channel blockers (CCBs), nifedipine, nicardipine, diltiazem and
      verapamil, were used to displace the binding of [3H]-U69593 ((5a, 7a,8b)-(+)-N
      methyl-N-(7-[1-pyrrolidinyl]-1-oxaspiro[4,5] dec-8-yl)-benzeneacetamide), a
      specific kappa-opioid agonist, in the rat cardiac sarcolemma. The CCBs competed
      with the binding of [3H]-U69593 (4 nM) in a dose-dependent manner. The displacing
      potency of verapamil was 55 times greater than that of nifedipine. 2. The effects
      of two CCBs, verapamil and nifedipine, on the arrhythmogenic action of kappa
      receptor stimulation by a specific kappa-receptor agonist, U50,488H (trans-(+/-(
      3),4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl] cyclohexyl) benzeacetamide
      methanesulphonate), were also studied in the rat isolated perfused heart.
      U50,488H 80-800 nmol dose-dependently induced arrhythmias, which were completely
      abolished by a selective kappa-receptor antagonist, nor-BNI (nor-binaltorphimine,
      17,17'-(dicyclopropylmethyl)-6,6',7,7'-6,6'-imino-7,7'-binorphinan -3,4',14, 14'
      tetrol), at 100 nmol. The arrhythmogenic effect was also attenuated by both
      verapamil and nifedipine in a dose-dependent manner. The ED50 values for
      verapamil and nifedipine were 2.75 and 63.7 nmol, respectively. The
      antiarrhythmic potencies of these two CCBs were correlated to their displacing
      potencies and inversely related to their well known potencies in inhibiting
      transmembrane Ca2+ influx in the cardiac muscle. 3. Measurement of [Ca2+]i in the
      absence of free extracellular Ca2+ by a spectrofluorometric method, with fura-2
      as Ca2+ indicator, showed that U50,488H 5 x 10(-5) M slowly increased [Ca2+]i in
      single ventricular myocytes and this effect was abolished by pretreatment with
      nor-BNI (5 microM), or ryanodine (5 microM). Verapamil 1 and 10 microM abolished
      the effect of U50,488H in 37.5% (3 out of 8) and 100% (12 out of 12) of the cells
      studied, respectively. On the other hand, nifedipine 10 and 100 microM had no
      effect at all. Neither verapamil nor nifedipine exerted any significant effect on
      the caffeine-induced Ca2+ transient. 4. The observations suggest that CCBs may
      inhibit the actions of kappa-receptor stimulation at the level of the kappa
      receptor.

PMID- 9138689
TI  - Spermine modulation of specific [3H]-gabapentin binding to the detergent
      solubilized porcine cerebral cortex alpha 2 delta calcium channel subunit.
AB  - 1. Recent studies have identified the [3H]-gabapentin-binding protein, purified
      from porcine cerebral cortical membranes, as the alpha 2 delta subunit of voltage
      sensitive calcium channels (Gee et al., 1996). The present study investigates the
      influence of the polyamine spermine on specific [3H]-gabapentin binding to
      detergent-solubilized porcine cerebral cortical membranes. 2. Spermine,
      spermidine, 1,10 diaminodecane, Mg2+ and Zn2+, all divalent cations, displaced
      [3H]-gabapentin binding to detergent-solubilized membranes in a concentration
      dependent manner with a maximal inhibition of 65-75%. Radioligand binding studies
      showed that spermine did not directly interact with the [3H]-gabapentin-binding
      site. Spermine inhibited [3H]-gabapentin binding by interacting with a polyamine
      sensitive allosteric site on the membrane protein. The steep concentration
      dependence of spermine inhibition of [3H]-gabapentin binding may suggest multi
      site co-operativity. 3. Prolonged dialysis of cerebral cortical membranes and
      Tween 20-solubilized membranes resulted in a > 2.0 fold increase in [3H]
      gabapentin binding. The increase in binding was due to the removal of a heat
      stable, low molecular weight (< 12,000Da) endogenous molecule which influences
      [3H]-gabapentin binding competitively. 4. Dialysis of detergent-solubilized
      cerebral cortical membranes also resulted in a decrease in the maximum inhibition
      of [3H]-gabapentin binding by spermine. Since the rates of the increase in [3H]
      gabapentin binding and the loss of the ability of spermine to inhibit [3H]
      gabapentin binding on dialysis were different it was inferred that a second
      endogenous ligand was removed during dialysis. 5. During initial steps of
      purification of the [3H]-gabapentin-binding protein there was a decrease in the
      maximum inhibition of [3H]-gabapentin binding by spermine. The loss of the second
      endogenous molecule during initial purification would reasonably explain the
      reduction in inhibition of binding by spermine. However, spermine stimulation of
      [3H]-gabapentin binding to material that eluted from the gel-filtration column
      later in the purification scheme does not appear to be due to removal of a
      dialysable endogenous factor or to the dissociation of other calcium channel
      subunit(s). 6. Adding back dialysate, before or after boiling, to detergent
      solubilized membranes resulted in a dose-dependent restoration of the inhibition
      of [3H]-gabapentin binding and of the maximal inhibition [3H]-gabapentin binding
      by spermine. This result is consistent with the re-addition of two endogenous
      heat stable ligands. 7. The findings that [3H]-gabapentin binding to the pure
      alpha 2 delta subunit was stimulated by spermine indicates that the alpha 2 delta
      subunit of voltage-sensitive calcium channels bears a modulatory spermine site.
      Such a spermine site has not been identified before. Spermine stimulation of [3H]
      gabapentin binding to the purified protein was reversed to inhibition after
      adding back dialysate. Thus the inhibitory spermine effect in membranes is also
      probably due to one or more modulatory sites on the alpha 2 delta subunit.

PMID- 9138690
TI  - The effects of bradykinin on K+ currents in NG108-15 cells treated with U73122, a
      phospholipase C inhibitor, or neomycin.
AB  - 1. Bradykinin has multiple effects on differentiated NG108-15 neuroblastoma x
      glioma cells: it increases Ins(1,4,5)P3 production and intracellular Ca2+
      concentration [Ca2+]i evokes a Ca2+ activated K+ current (IK(Ca)) and inhibits M
      current (IM). We studied the effect of the aminosteroid U73122 and the antibiotic
      neomycin, both putative blockers of phospholipase C (PLC), on these four
      bradykinin effects. 2. Preincubation with 1 or 5 microM U73122 for 15 min partly
      suppressed Ins(1,4,5)P3 generation and the increase in [Ca2+]i induced by 1
      microM bradykinin. U73122 10 microM caused total and irreversible inhibition. The
      inactive analogue U73343 was without effect. 3. Resting levels of Ins(1,4,5)P3
      were not affected. However, resting [Ca2+]i was increased by 10 microM U73122,
      but not by U73343. Individual cells responded to 10 microM U73122 with a small
      increase in [Ca2+]i, followed in some cells by a large further rise. 4.
      Pretreatment of whole-cell clamped cells with 1 microM U73122 for 30 min reduced
      the bradykinin-induced IK(Ca) to a fifth of its normal size. To suppress it
      totally, a 7-12 min pretreatment with 5 microM U73122 was required. Again, U73343
      was without effect. 5. U73122 and U73343 at concentrations of 5-10 microM
      irreversibly decreased the holding current (Ih) which at a holding potential of 
      30 or -20 mV mainly flows through open M channels. The decrease was often
      preceded by a transient increase. 6. M current (IM) measured with 1 s pulses, was
      also decreased by 5-10 microM U73122 and U73343, but short applications of U73122
      could cause a small increase. The bradykinin-induced inhibition of IM was not
      affected by U73122. 7. Preincubation with 1 or 3 mM neomycin for 15 min did not
      affect Ins(1,4,5)P3 generation and the increase in [Ca2+]i induced by bradykinin.
      Pretreatment with 3 mM neomycin for about 20 min diminished the bradykinin
      induced IK(Ca) to a fifth of its normal size. 8. The four main conclusions drawn
      from the results are: (a) U73122 suppresses bradykinin-induced PLC activation and
      IK(Ca), but not IM inhibition. (b) This indicates that the transient outward
      current IK(Ca), but not the decrease of IM in response to bradykinin, is mediated
      by PLC. (c) U73122 itself inhibits IM and mobilizes Ca2+ from intracellular
      stores. (d) Externally applied neomycin is not an effective inhibitor of PLC
      mediated signalling pathways in NG108-15 cells.

PMID- 9138691
TI  - The involvement of a novel mechanism distinct from the thrombin receptor in the
      vasocontraction induced by trypsin.
AB  - 1. The vasocontracting effect of a serine protease trypsin and its mechanisms
      were investigated by monitoring the isometric tension in endothelium-denuded
      rings of rabbit thoracic aortae and its effects on intracellular free Ca2+
      concentrations ([Ca2+]i) in dispersed rabbit vascular smooth muscle cells with a
      Ca2+ indicator fura-2. The actions of trypsin were compared with those of
      thrombin. 2. Both thrombin and trypsin reversibly contracted aortic rings without
      endothelium in a concentration-dependent manner. The vasocontraction induced by
      trypsin was well correlated with the protease activity of trypsin actually added
      to the tissue baths containing the aortic rings and was completely blocked by
      soybean trypsin inhibitor and phenylmethylsulphonyl fluoride (PMSF), a serine
      protease inhibitor. 3. The trypsin-induced contractions of the aortic rings were
      not the result of irreversible damage to vascular smooth muscle cells, since the
      contractile responses induced by noradrenaline or 30 mM KCl were unaffected by
      pretreatment with trypsin. 4. The contractions induced by either thrombin or
      trypsin were reduced to about 30% of control responses after removal of
      extracellular Ca2+, indicating that most of the contraction is dependent on
      extracellular Ca2+. By contrast, the contractions induced by either of the
      proteases were reduced by an antagonist of L-type voltage-operated Ca2+ channels,
      nifedipine, to about 70% of control responses, indicating that both nifedipine
      sensitive and -resistant Ca2+ channels are involved in these contractions. 5. In
      the aortic rings precontracted by a maximally effective concentration of
      thrombin, the second application of thrombin virtually failed to induce
      contractions but trypsin could still induce contractions amounting to 10% of
      control values by it's protease activity. 6. After the first application of a
      maximal concentration of thrombin, the second application of thrombin could not
      induce an increase in [Ca2+]i, but an application of trypsin could still induce
      an increase in [Ca2+]i in dispersed rabbit vascular smooth muscle cells. 7. These
      data suggest that in addition to activation of a thrombin receptor, trypsin can
      contract rabbit aortae by a proteinase-activated receptor 2 or a novel mechanism.

PMID- 9138692
TI  - Endothelium-independent relaxation of aortic rings by the nitric oxide synthase
      inhibitor diphenyleneiodonium.
AB  - 1. The flavoprotein binder diphenyleneiodonium (DPI) is a potent, irreversible
      inhibitor of nitric oxide synthase (NOS), but produces only a transient pressor
      response following systemic administration to animals, despite evidence of
      persistent NOS inhibition. To characterize further the effects of DPI on vascular
      tone, isometric tension was recorded from rat isolated aortic rings mounted
      between steel wires in an organ bath. 2. The NOS inhibitor NG-nitro-L-arginine
      methyl ester (L-NAME, 1 mM) initiated an additional contraction of prostaglandin
      F2 alpha-preconstricted rings with endothelium which was sustained throughout the
      period of L-NAME exposure (+234 +/- 39% at 15 min). In contrast, addition of DPI
      (5 microM) to rings with endothelium produced a transient initial contraction
      (+111 +/- 27% at 2 min) followed by a more sustained relaxation (-27 +/- 19% at
      15 min, P < 0.001 vs L-NAME). 3. The contraction to DPI was also observed in
      rings without endothelium, was abolished by L-NAME pretreatment, and was
      unaffected by the alpha-adrenoreceptor inhibitor prazosin. Relaxation in response
      to DPI was not inhibited by endothelium removal or by pretreatment with either L
      NAME or with the ATP-sensitive potassium channel blocker glibenclamide. 4. The
      endothelium-independent relaxation to DPI was inhibited at 23 degrees C and its
      time course was delayed by pretreatment with the guanylate cyclase inhibitor
      methylene blue. 5. Thus, in addition to a transient initial contraction due to
      NOS inhibition, DPI produces an endothelium-independent, temperature-dependent
      relaxation which appears in part due to activation of guanylate cyclase. This
      relaxant effect of DPI may explain the transient nature of its pressor effect in
      vivo despite sustained NOS inhibition.

PMID- 9138693
TI  - Modulation of the firing activity of noradrenergic neurones in the rat locus
      coeruleus by the 5-hydroxtryptamine system.
AB  - 1. The aim of the present study was to investigate the putative modulation of
      locus coeruleus (LC) noradrenergic (NA) neurones by the 5-hydroxytryptaminergic
      (5-HT) system by use of in vivo extracellular unitary recordings and
      microiontophoresis in anaesthetized rats. To this end, the potent and selective 5
      HT1A receptor antagonist WAY 100635 (N-[2-[4(2-methoxyphenyl)-1-piperazinyl]-N-(2
      pyridinyl) cyclohexanecarboxamide trihydroxychloride) was used. 2. In the dorsal
      hippocampus, both local (by microiontophoresis, 20 nA) and systemic (100
      micrograms kg-1, i.v.) administration of WAY 100635 antagonized the suppressant
      effect of microiontophorectically-applied 5-HT on the firing activity of CA3
      pyramidal neurones, indicating its antagonistic effect on postsynaptic 5-HT1A
      receptors. 3. WAY 100635 and 5-HT failed to modify the spontaneous firing
      activity of LC NA neurones when applied by microiontophoresis. However, the
      intravenous injection of WAY 100635 (100 micrograms kg-1) readily suppressed the
      spontaneous firing activity of LC NA neurones. 4. The lesion of 5-HT neurones
      with the neurotoxin 5,7-dihydroxytryptamine increased the spontaneous firing
      activity of LC NA neurones and abolished the suppressant effect of WAY 100635 on
      the firing activity of LC NA neurones. 5. In order to determine the nature of the
      5-HT receptor subtypes mediating the suppressant effect of WAY 100635 on NA
      neurone firing activity, several 5-HT receptor antagonists were used. The
      selective 5-HT3 receptor antagonist BRL 46470A (10 and 100 micrograms kg-1,
      i.v.), the 5-HT1D receptor antagonist GR 127935 (100 micrograms kg-1, i.v.) and
      the 5-HT1A/1B receptor antagonist (-)-pindolol (15 mg kg-1, i.p.) did not prevent
      the suppressant effect of WAY 100635 on the firing activity of LC NA neurones.
      However, the suppressant effect of WAY 100635 was prevented by the non-selective
      5-HT receptor antagonists spiperone (1 mg kg-1, i.v.) and metergoline (1 mg kg-1,
      i.v.), by the 5-HT2 receptor antagonist ritanserin (500 micrograms kg-1, i.v.).
      It was also prevented by the 5-HT1A receptor/alpha 1D-adrenoceptor antagonist BMY
      7378 (1 mg kg-1, i.v.) and by the alpha 1-adrenoceptor antagonist prazosin (100
      micrograms kg-1, i.v.). 6. These data support the notion that the 5-HT system
      tonically modulates NA neurotransmission since the lesion of 5-HT neurones
      enhanced the LC NA neurones firing activity and the suppressant effect of WAY
      100635 on the firing activity of NA neurones was abolished by this lesion.
      However, the location of the 5-HT1A receptors involved in this complex circuitry
      remains to be elucidated. It is concluded that the suppressant effect of WAY
      100635 on the firing activity of LC NA neurones is due to an enhancement of the
      function of 5-HT neurones via a presynaptic 5-HT1A receptor. In contrast, the
      postsynaptic 5-HT receptor mediating this effect of WAY 100635 on NA neurones
      appears to be of the 5-HT2A subtype.

PMID- 9138694
TI  - Visual detection of transport-P in peptidergic neurones.
AB  - 1. Hypothalamic peptidergic neurones possess an uptake process for amines
      (transport-P), for which prazosin is a substrate. It is characterized by a
      paradoxical increase in the accumulation of [3H]-prazosin when the concentration
      of unlabelled prazosin is increased above 10(-7) M. This increase is due to
      activation of a proton-dependent, vacuolar-type ATPase-linked pump that is
      blocked by tricyclic antidepressants. This study utilized a fluorescence method
      to detect amine uptake in individual cells. 2. Prazosin is fluorescent but most
      of its emission spectrum is in the ultraviolet range. We therefore used an
      analogue of prazosin in which the furan ring had been substituted with a
      fluorescent group, BODIPY FL. This compound's emission maximum is in the green
      part of the visible spectrum. 3. BODIPY FL prazosin accumulated in immortalised
      peptidergic neurones and the characteristic emission spectrum of the compound was
      evident in these cells. Accumulation of BODIPY FL prazosin was saturable and was
      inhibited by the tricyclic antidepressant desipramine and by unlabelled prazosin.
      As previously described for prazosin, uptake of BODIPY FL prazosin was blocked by
      cold temperature and by the organic base chloroquine. Thus, prazosin and BODIPY
      FL prazosin were accumulated by the same uptake process. 4. BODIPY FL prazosin
      accumulated in a granular distribution, which is compatible with storage in
      intracellular vesicles. 5. Hypothalamic cells from foetal rats in primary culture
      also accumulated BODIPY FL prazosin by a desipramine-sensitive process. Uptake
      was predominantly in neurones and glial cells did not accumulate the amine. 6.
      Fluorescent detection provides visual evidence for amine uptake in peptidergic
      neurones and should enable detailed study of the distribution of this process in
      the brain.

PMID- 9138695
TI  - Localization of leukaemia inhibitory factor to airway epithelium and its
      amplification of contractile responses to tachykinins.
AB  - 1. In neural tissue, leukaemia inhibitory factor (LIF) is an important trophic
      cytokine. In this investigation, we determined if LIF was present in human and
      guinea-pig airways and examined the role of this cytokine in modulating airway
      responses to endogenous and exogenous tachykinins as well as muscarinic receptor
      and beta-adrenoceptor stimulation. 2. The presence of LIF in both human and
      guinea-pig airways was determined by immunohistochemistry. Guinea-pig tracheal
      explants were incubated in CRML-1066 media containing LIF (0.5, 5 or 50 ng ml-1)
      for periods of 3, 6, 24 and 48 h. Tracheal rings were then transferred to organ
      baths for measurement of isometric force in response to carbachol, capsaicin, the
      neurokinin1 (NK1) receptor agonist [Sar9,Met(O2)11]-substance P (SP), the NK2
      receptor agonist neurokinin A (NKA) and isoprenaline. 3. LIF immunoreactivity was
      observed primarily in basally situated cells in the airway epithelium of both
      large and small airways. Less intense immunoreactivity was observed in vascular
      endothelium and glandular epithelium. 4. Treatment with LIF (0.5 ng ml-1) for 3
      and 6 h significantly increased contractile responses to capsaicin by 42% and
      43%, respectively, compared to time controls, whereas higher concentrations of
      LIF (5 and 50 ng ml-1) enhanced capsaicin-induced contractions only after 6 h.
      After 24 h, responses to capsaicin were not significantly different from 0 h
      control. Contractile responses to capsaicin following exposure to LIF at any
      concentration for 24 h were not significantly different from relative time
      control values. 5. Responses to [Sar9,Met(O2)11]-SP, carbachol and isoprenaline
      were not influenced by time in culture or by exposure to LIF for up to 48 h.
      Contractile responses induced by NKA were not influenced by 3 or 6 h exposure to
      LIF, but at 24 and 48 h the mean maximum contractile responses to NKA were
      significantly increased by 33% and 35%, respectively, compared to control. 6.
      These results demonstrate that LIF is present in guinea-pig and human airway
      epithelium, and modulates airway responses to tachykinins. In the acute setting
      LIF augments the capsaicin-induced release of endogenous tachykinins, whilst in
      the longer term (> 24 h), LIF increases airway smooth muscle responses to
      tachykinins via an NK2 receptor selective mechanism. We conclude that LIF may be
      an important effector molecule in the response of airways to injury or
      inflammation.

PMID- 9138696
TI  - Role of alpha 2-adrenoceptors in the regulation of intestinal water transport.
AB  - 1. The influence of the sympathetic nervous system on intestinal fluid transport
      by the jejunum and ileum of the anaesthetized rat was investigated under basal
      conditions and during active secretion induced by intra-arterial infusion of
      vasoactive intestinal peptide (VIP). 2. Intra-arterial infusion of noradrenaline
      (3, 10, 30 nmol min-1, i.a.) and i.v. injection of the selective alpha 2
      adrenoceptor agonist UK 14,304 (1 mumol kg-1, i.v.) increased the rate of basal
      fluid absorption. The effect of UK 14,304 was blocked by yohimbine (10 mumol kg
      1, i.v.). However, the selective alpha 1-adrenoceptor agonist phenylephrine (5
      mumol kg-1, i.v.) did not alter either the jejunal or ileal absorption rate. 3.
      The alpha 2-adrenoceptor antagonists yohimbine (0.3, 1.0, 3 and 10 mumol kg-1,
      i.v.) and rauwolscine (10 mumol kg-1, i.v.) decreased the basal absorption rate,
      while the alpha 1-adrenoceptor antagonist prazosin (3 mumol kg-1, i.v.) was
      without effect. Intracerebroventricular injection of yohimbine (3 mumol kg-1)
      caused a significant antiabsorptive effect in the jejunum but not ileum. 4.
      Peripheral chemical sympathectomy induced by pretreating animals with 6
      hydroxydopamine (150 mg kg-1, i.p., total dose) induced a trend towards impaired
      absorption in the jejunum and ileum. 5. The findings provide evidence that the
      sympathetic nervous system exerts tonic control on intestinal fluid transport and
      that the effect is mainly through peripheral alpha 2-adrenoceptors. 6. The
      subtype determination of alpha 2-adrenoceptors in modulating intestinal fluid
      transport was assessed by determining the effects of alpha 2-adrenoceptor agents
      on intestinal fluid secretion induced by i.a. infusion of VIP (0.8 microgram min
      1). 7. Intravenous administration of UK 14,304 caused a dose-dependent reversal
      of the secretory phase of the VIP-induced response, but failed to restore fluid
      transport to the control level of net absorption. EC50 values were 0.17 mumol kg
      1 in the jejunum and 0.22 mumol kg-1 in the ileum. 8. The effect of UK 14,304 was
      blocked by the selective alpha 2A/D antagonist BRL 44408 and the nonselective
      alpha 2 antagonist yohimbine (each 10 mumol kg-1). The selective alpha 2B/C
      antagonist ARC 239 (10 mumol kg-1) did not affect the antisecretory action of UK
      14,304. It is suggested that the alpha 2-adrenoceptors in the rat intestinal
      epithelium are the alpha 2D or alpha 2A-like subtype.

PMID- 9138697
TI  - Modulation by general anaesthetics of rat GABAA receptors comprised of alpha 1
      beta 3 and beta 3 subunits expressed in human embryonic kidney 293 cells.
AB  - 1. Radioligand binding and patch-clamp techniques were used to study the actions
      of gamma-aminobutyric acid (GABA) and the general anaesthetics propofol (2,6
      diisopropylphenol), pentobarbitone and 5 alpha-pregnan-3 alpha-ol-20-one on rat
      alpha 1 and beta 3 GABAA receptor subunits, expressed either alone or in
      combination. 2. Membranes from HEK293 cells after transfection with alpha 1 cDNA
      did not bind significant levels of [35S]-tert-butyl bicyclophosphorothionate
      ([35S]-TBPS) (< 0.03 pmol mg-1 protein). GABA (100 microM) applied to whole-cells
      transfected with alpha 1 cDNA and clamped at -60 mV, also failed to activate
      discernible currents. 3. The membranes of cells expressing beta 3 cDNAs bound
      [35S]-TBPS (approximately 1 pmol mg-1 protein). However, the binding was not
      influenced by GABA (10 nM-100 microM). Neither GABA (100 microM) nor picrotoxin
      (10 microM) affected currents recorded from cells expressing beta 3 cDNA,
      suggesting that beta 3 subunits do not form functional GABAA receptors or
      spontaneously active ion channels. 4. GABA (10 nM-100 microM) modulated [35S]
      TBPS binding to the membranes of cells transfected with both alpha 1 and beta 3
      cDNAs. GABA (0.1 microM-1 mM) also dose-dependently activated inward currents
      with an EC50 of 9 microM recorded from cells transfected with alpha 1 and beta 3
      cDNAs, clamped at -60 mV. 5. Propofol (10 nM-100 microM), pentobarbitone (10 nM
      100 microM) and 5 alpha-pregnan-3 alpha-ol-20-one (1 nM-30 microM) modulated
      [35S]-TBPS binding to the membranes of cells expressing either alpha 1 beta 3 or
      beta 3 receptors. Propofol (100 microM), pentobarbitone (1 mM) and 5 alpha
      pregnan-3 alpha-ol-20-one (10 microM) also activated currents recorded from cells
      expressing alpha 1 beta 3 receptors. 6. Propofol (1 microM-1 mM) and
      pentobarbitone (1 mM) both activated currents recorded from cells expressing beta
      3 homomers. In contrast, application of 5 alpha-pregnan-3 alpha-ol-20-one (10
      microM) failed to activate detectable currents. 7. Propofol (100 microM)
      activated currents recorded from cells expressing either alpha 1 beta 3 or beta 3
      receptors reversed at the Cl- equilibrium potential and were inhibited to 34 +/-
      13% and 39 +/- 10% of control, respectively, by picrotoxin (10 microM). 5 alpha
      Pregnan-3 alpha-ol-20-one (100 nM) enhanced propofol (100 microM)-evoked currents
      mediated by alpha 1 beta 3 receptors to 1101 +/- 299% of control. In contrast,
      even at high concentration 5 alpha-pregnan-3 alpha-ol-20-one (10 microM) caused
      only a modest facilitation (to 128 +/- 12% of control) of propofol (100 microM)
      evoked currents mediated by beta 3 homomers. 8. Propofol (3-100 microM) activated
      alpha 1 beta 3 and beta 3 receptors in a concentration-dependent manner. For both
      receptor combinations, higher concentrations of propofol (300 microM and 1 mM)
      caused a decline in current amplitude. This inhibition of receptor function
      reversed rapidly during washout resulting in a "surge' current on cessation of
      propofol (300 microM and 1 mM) application. Surge currents were also evident
      following pentobarbitone (1 mM) application to cells expressing either receptor
      combination. By contrast, this phenomenon was not apparent following applications
      of 5 alpha-pregnan-3 alpha-ol-20-one (10 microM) to cells expressing alpha 1 beta
      3 receptors. 9. These observations demonstrate that rat beta 3 subunits form
      homomeric receptors that are not spontaneously active, are insensitive to GABA
      and can be activated by some general anaesthetics. Taken together, these data
      also suggest similar sites on GABAA receptors for propofol and barbiturates, and
      a separate site for the anaesthetic steroids.

PMID- 9138698
TI  - Induction of cyclo-oxygenase-2 by cytokines in human cultured airway smooth
      muscle cells: novel inflammatory role of this cell type.
AB  - 1. Cyclo-oxygenase (COX) is the enzyme that converts arachidonic acid to
      prostaglandin H2 (PGH2) which can then be further metabolized to prostanoids
      which modulate various airway functions. COX exists in at least two isoforms. COX
      1 is expressed constitutively, whereas COX-2 is expressed in response to pro
      inflammatory stimuli. Prostanoids are produced under physiological and
      pathophysiological conditions by many cell types in the lung. However, the
      regulation of the different COX isoforms in human airway smooth muscle (HASM)
      cells has not yet been determined. 2. COX-1 and COX-2 protein were measured by
      Western blot analysis with specific antibodies for COX-1 and COX-2. COX-2 mRNA
      levels were assessed by Northern blot analysis by use of a COX-2 cDNA probe. COX
      activity was determined by measuring conversion of either endogenous or exogenous
      arachidonic acid to three metabolites, PGE2, thromboxane B2 or 6-ketoPGF1 alpha
      by radioimmunoassay. 3. Under control culture conditions HASM cells expressed COX
      1, but not COX-2, protein. However, a mixture of cytokines (interleukin-1 beta
      (IL-1 beta), tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFN
      gamma) each at 10 ng ml-1) induced COX-2 mRNA expression, which was maximal at 12
      h and inhibited by dexamethasone (1 microM; added 30 min before the cytokines).
      Furthermore, COX-2 protein was detected 24 h after the cytokine treatment and the
      expression of this protein was also inhibited by dexamethasone (1 microM) and
      cyclohexamide (10 micrograms ml-1; added 30 min before the cytokines). 4.
      Untreated HASM cells released low or undetectable amounts of all COX metabolites
      measured over a 24 h period. Incubation of the cells with the cytokine mixture
      (IL-1 beta, TNF alpha, IFN gamma each at 10 ng ml-1 for 24 h) caused the
      accumulation of PGE2 and 6-keto-PGF1 alpha. 5. In experiments where COX-2
      metabolized endogenous stores of arachidonic acid, treatment of HASM cells with
      IL-1 beta in combination with TNF alpha caused a similar release of PGE2 to that
      when the three cytokines were given in combination. 6. In other experiments
      designed to measure COX-2 activity directly, cells were treated with cytokines
      for 24 h before fresh culture medium was added containing exogenous arachidonic
      acid (30 microM for 15 min) after which PGE2 was measured. IL-1 beta and TNF
      alpha increased COX-2 activity and an additional small increase was produced by
      the three cytokines in combination. 7. These findings suggest that the increased
      expression of COX-2 is intimately involved in the exaggerated release of
      prostanoids from HASM cells exposed to pro-inflammatory cytokines. These data
      indicate a role for airway smooth muscle cells, in addition to their contractile
      function, as inflammatory cells involved in the production of mediators which may
      contribute to the inflammatory response seen in diseases such as asthma.

PMID- 9138699
TI  - Cellular localization of the inhibitory action of abruquinone A against
      respiratory burst in rat neutrophils.
AB  - 1. The possible mechanisms of action of the inhibitory effect of abruquinone A on
      the respiratory burst in rat neutrophils in vitro was investigated. 2.
      Abruquinone A caused an irreversible and a concentration-dependent inhibition of
      formylmethionylleucyl-phenylalanine (fMLP) plus dihydrocytochalasin B (CB)- and
      phorbol 12-myristate 13-acetate (PMA)-induced superoxide anion (O2.-) generation
      with IC50 values of 0.33 +/- 0.05 microgram ml-1 and 0.49 +/- 0.04 microgram ml
      1, respectively. 3. Abruquinone A also inhibited O2 consumption in neutrophils in
      response to fMLP/CB and PMA. However, abruquinone A did not scavenge the
      generated O2.- in xanthine-xanthine oxidase system and during dihydroxyfumaric
      acid (DHF) autoxidation. 4. Abruquinone A inhibited both the transient elevation
      of [Ca2+]i in the absence of [Ca2+]o (IC50 7.8 +/- 0.2 micrograms ml-1) and the
      generation of inositol trisphosphate (IP3) (IC50 10.6 +/- 2.0 micrograms ml-1) in
      response to fMLP. 5. Abruquinone A did not affect the enzyme activaties of
      neutrophil cytosolic protein kinase C (PKC) and porcine heart protein kinase A
      (PKA). 6. Abruquinone A had no effect on intracellular guanosine 3':5'-cyclic
      monophosphate (cyclic GMP) levels but decreased the adenosine 3':5'-cyclic
      monophosphate (cyclic AMP) levels. 7. The cellular formation of phosphatidic acid
      (PA) and phosphatidylethanol (PEt) induced by fMLP/ CB was inhibited by
      abruquinone A with IC50 values of 2.2 +/- 0.6 micrograms ml-1 and 2.5 +/- 0.3
      micrograms ml-1, respectively. Abruquinone A did not inhibit the fMLP/CB-induced
      protein tyrosine phosphorylation but induced additional phosphotyrosine
      accumulation on proteins of 73-78 kDa in activated neutrophils. 8. Abruquinone A
      inhibited both the O2.- generation in PMA-activated neutrophil particulate NADPH
      oxidase (IC50 0.6 +/- 0.1 microgram ml-1) and the iodonitrotetrazolium violet
      (INT) reduction in arachidonic acid (AA)-activated cell-free system (IC50 1.5 +/-
      0.2 micrograms ml-1) 9. Collectively, these results indicate that the inhibition
      of respiratory burst in rat neutrophils by abruquinone A is mediated partly by
      the blockade of phospholipase C (PLC) and phospholipase D (PLD) pathways, and by
      suppressing the function of NADPH oxidase through the interruption of electron
      transport.

PMID- 9138700
TI  - The effect of the putative endogenous imidazoline receptor ligand, clonidine
      displacing substance, on insulin secretion from rat and human islets of
      Langerhans.
AB  - 1. The effects of a rat brain extract containing clonidine-displacing substance
      (CDS), a putative endogenous imidazoline receptor ligand, on insulin release from
      rat and human isolated islets of Langerhans were investigated. 2. CDS was able to
      potentiate the insulin secretory response of rat islets incubated at 6 mM
      glucose, in a dose-dependent manner. The magnitude of this effect was similar to
      that in response to the well-characterized imidazoline secretagogue, efaroxan. 3.
      CDS, like other imidazoline secretagogues, was also able to reverse the
      inhibitory action of diazoxide on glucose-induced insulin release, in both rat
      and human islets. 4. These effects of CDS on secretion were reversed by the
      imidazoline secretagogue antagonists, RX801080 and the newly defined KU14R,
      providing the first evidence that imidazoline-mediated actions of CDS can be
      blocked by specific imidazoline antagonists. 5. The effects of CDS on insulin
      secretion were unaffected when the method of preparation involved centri
      filtration through a 3,000 Da cut-off membrane or when the extract was treated
      with protease. These results confirm that the active principle is of low
      molecular weight and is not a peptide. 6. Overall, the data suggest that CDS
      behaves as a potent endogenous insulin secretagogue acting at the islet
      imidazoline receptor.

PMID- 9138701
TI  - Effects of FR173657, a non-peptide B2 antagonist, on kinin-induced hypotension,
      visceral and peripheral oedema formation and bronchoconstriction.
AB  - 1. Kinins are believed to play a key role in many inflammatory conditions.
      Therefore, bradykinin antagonists are being developed for potential therapeutic
      applications. In the present investigation we describe the pharmacology, in vivo,
      of (E)-3-(6-acetamido-3-pyridyl)-N-[N-[2,4-dichloro-3-[2-methyl-8-quinoliny l)
      oxymethyl]phenyl]-N-methylaminocarbonylmethyl]acrylamide (FR173657), a novel, non
      peptide bradykinin antagonist. 2. The hypotensive effects of i.v. injections of
      bradykinin (50 pmol) in captopril-pre-treated anaesthetized rats were
      significantly inhibited by 100 nmol kg-1 FR173657 s.c., and completely abolished
      by 300 nmol kg-1. The full inhibitory effect developed within 60 min and remained
      unchanged for at least 4 h. However, the effect was reversible, since 24 h after
      an injection of 300 nmol kg-1 FR173657 no inhibitory effect could be observed. 3.
      The plasma protein extravasation into the pancreas and duodenum induced by an
      i.v. infusion of bradykinin (11 nmol kg-1 within 20 min) in captopril-treated
      anaesthetized rats was completely abolished by FR173657 at doses of 30 nmol kg-1
      s.c. and above, given 60 min before bradykinin. FR173657 3 nmol kg-1 was
      ineffective, while a dose of 10 nmol kg-1 produced an intermediate effect. 4. The
      paw oedema induced by the subplantar injection of bradykinin (30 nmol) in
      anaesthetized rats was inhibited slightly by s.c. injection of FR173657 0.3 mumol
      kg-1, whereas 1 and 3 mumol kg-1 produced significant inhibition of the
      bradykinin-induced oedema. The maximum inhibition amounted to about 50% and could
      not be increased even when the dose of FR173657 was increased to 30 mumol kg-1.
      FR173657 did not effect the oedema caused by histamine or 5-hydroxytryptamine. 5.
      Bradykinin (20 nmol kg-1, i.v.) caused increases in pulmonary inflation pressure
      by 300-600 Pa in anaesthetized, respirated guinea-pigs. The effect was reduced to
      58 +/- 9% of the initial value 60 min after the s.c. injection of FR173657 1
      mumol kg-1, whereas only 9 +/- 7% remained after 10 mumol kg-1. The
      bronchoconstrictor actions of histamine remained unaffected by FR173657. 6. In
      summary, FR173657 is a highly potent and selective bradykinin antagonist. The
      inhibitory action in vivo lasts for longer than 4 h but is fully reversible.
      FR173657, or similar compounds, will be a useful tool for the pharmacological
      investigation of pathophysiological states and may possess a therapeutic
      potential in diseases involving the endogenous release of kinins.

PMID- 9138702
TI  - Differential regulation by protein kinase C isoforms of nitric oxide synthase
      induction in RAW 264.7 macrophages and rat aortic smooth muscle cells.
AB  - 1. In RAW 264.7 murine macrophages and rat aortic smooth muscle (RASM) cells
      lipopolysaccharide (LPS) alone or in combination with interferon gamma (IFN
      gamma) or forskolin, respectively, stimulated the expression of the 130 kDa
      inducible isoform of nitric oxide synthase (iNOS) in both a time- and
      concentration-dependent manner. 2. Incubation with the direct activator of
      protein kinase C (PKC), phorbol 12-myristate 13-acetate (PMA) alone, did not
      result in detectable iNOS expression in either cell type. 3. Chronic PMA
      pretreatment resulted in significant down-regulation of alpha, beta and epsilon
      isforms of PKC in RAW 264.7 macrophages and corresponded to a 20-30% reduction in
      LPS-induced iNOS expression. In contrast, IFN gamma alone or in combination with
      LPS stimulated an approximate 20% and 50% potentiation, respectively. 4. Pre
      incubation with PKC inhibitors (calphostin C and H-7) showed similar effects upon
      stimulated induction of iNOS. 5. In RASM cells chronic PMA pretreatment resulted
      in down-regulation of alpha and epsilon PKC isoforms and corresponded to
      potentiation of iNOS expression in response to LPS alone or in combination with
      forskolin. 6. Co-incubation of RASM cells in the presence of PMA, angiotensin II
      (AII) or foetal calf serum (FCS) resulted in the inhibition of iNOS expression in
      response to LPS alone or in combination with forskolin. 7. Differential
      sensitivity to PKC inhibitors (calphostin C and H-7) was observed in RASM cells
      and exhibited both negative and positive modulation of stimulated induction. 8.
      In addition the PKC inhibitor compound Ro-31-8220 abolished stimulated induction
      in both cell types in response to all treatments. 9. These results suggest that
      PKC activation is required for induction of the 130 kDa isoform of NOS in both
      RAW 264.7 macrophages and RASM cells. However, individual PKC isoforms regulate
      iNOS expression in both a positive and negative manner.

PMID- 9138703
TI  - Renal adenosine A1 receptor binding characteristics and mRNA levels during the
      development of acute renal failure in the rat.
AB  - 1. The binding characteristics and mRNA levels for renal adenosine A1 receptors
      were investigated in normal rats and rats with acute renal failure (ARF) induced
      by either glycerol or HgCl2. 2. Saturation isotherms determined from the binding
      of [3H]-1,3-dipropyl-8-cyclopentylxanthine ([3H]-DPCPX), a selective adenosine A1
      antagonist, to renal membranes of untreated rats gave values of 0.62 nM for the
      equilibrium dissociation constant (Kd) and 19.9 fmol mg-1 protein for the density
      of binding sites (Bmax). No saturable binding was observed with [3H]-2-(p
      (carboxylethyl)-phenylethylamino)-5'-N-ethylcar box amido adenosine ([3H]-CGS
      21680), a selective adenosine A2a agonist. 3. By contrast to time-matched
      controls, renal membranes obtained from rats 16 and 48 h following the induction
      of ARF with glycerol, showed statistically significant increases (2-4 fold) in
      both Bmax and Kd for the binding of [3H]-DPCPX. No significant changes in the
      binding characteristics of [3H]-DPCPX were noted with membranes from rats 48 h
      following the production of ARF with HgCl2. 4. Adenosine A1 receptor mRNA levels
      were significantly elevated 0.5, 16 and 48 h following induction of ARF with
      glycerol, whilst no change was noted in mRNA levels for beta-actin at the same
      time points. No statistically significant changes in adenosine A1 receptor or
      beta-actin mRNA levels were noted 48 h after the induction of ARF with HgCl2. 5.
      This study indicates that glycerol-induced ARF in the rat is associated with an
      increase in renal adenosine A1 receptor density which appears to result from
      increased transcription of the gene for this receptor. An increase in adenosine
      A1 receptor density in renal resistance vessels may explain, at least in part,
      the enhanced renal vasoconstrictor response to adenosine in glycerol-induced ARF
      that was noted in a previous study.

PMID- 9138704
TI  - Vasoconstrictor responses via P2X-receptors are selectively antagonized by NF023
      in rabbit isolated aorta and saphenous artery.
AB  - 1. The effects of NF023, the symmetrical 3'-urea of 8-(benzamido)naphthalene
      1,3,5-trisulphonic acid), and its parent compound suramin were investigated on
      vasoconstrictor responses to alpha, beta-methylene ATP in rabbit isolated
      saphenous artery and vasodilator responses to ATP in noradrenaline-precontracted
      rabbit isolated thoracic aorta. 2. In rabbit isolated saphenous artery, alpha,
      beta-methylene ATP-induced vasoconstrictor responses via P2X-receptors were
      concentration-dependently and competitively antagonised by NF023 (30-300 microM;
      pA2 = 5.69 +/- 0.04). Suramin (100-1000 microM) also competitively blocked
      vasoconstrictor responses to alpha, beta-methylene ATP, albeit with lower potency
      (pA2 = 4.79 +/- 0.05). In contrast, NF023 (100 microM) did not significantly
      affect contractile responses to noradrenaline or histamine in the saphenous
      artery. 3. In noradrenaline-precontracted rabbit isolated thoracic aorta
      preparations, ATP (3-3000 microM) concentration-dependently induced relaxations
      via endothelium-dependent or smooth muscle P2Y-receptor subtypes. NF023 (30-300
      microM) failed to block relaxant responses to ATP at endothelium-dependent P2Y
      receptors, whereas suramin (100-1000 microM) did antagonise endothelium-dependent
      vasodilator responses to ATP. Neither NF023 (100 microM) nor suramin (300 microM)
      influenced vasorelaxant responses to ATP via endothelium-independent P2Y
      receptors. 4. In conclusion, this study outlines the selectivity of NF023 as an
      effective P2X-receptor antagonist in rabbit isolated blood vessels without
      affecting endothelium-dependent or endothelium-independent P2Y-receptor subtypes,
      adrenoceptors or histamine receptors.

PMID- 9138705
TI  - The duration of action of non-beta 2-adrenoceptor mediated responses to
      salmeterol.
AB  - 1. To investigate further the mechanism of the long duration of action of the
      selective beta 2-adrenoceptor agonist, salmeterol, we have determined the
      duration of action of some responses to salmeterol which are not mediated through
      beta 2-adrenoceptors. 2. In the presence of propranolol (1 microM), salmeterol (1
      30 microM) caused concentration-related relaxation of superfused, pre-contracted
      strips of guinea-pig gastric fundus. On washing the tissues, these relaxant
      responses were rapidly lost, the time to 50% recovery being approximately 30 min.
      3. In human neutrophils, salmeterol (1-100 microM) caused concentration-related
      inhibition of FMLP-induced O2- release. Propranolol (1 microM) had little or no
      effect on the inhibitory activity of salmeterol. Washing the cells twice over a
      40 min period caused a marked reduction of the inhibitory activity of salmeterol.
      4. In guinea-pig superfused trachea, in the absence of propranolol, infusions of
      (RS)-salmeterol (10-30 nM) and the less potent (S)-enantiomer of salmeterol (300
      3000 nM) inhibited electrically-induced contractile responses. When the infusion
      was stopped, there was no recovery from the inhibitory responses within 200 min.
      In the presence of propranolol (1 microM), infusions of (RS)-salmeterol (10
      microM) and (S)-salmeterol (10-100 microM) also inhibited the contractile
      responses, but, in contrast, on stopping the infusions differences were observed
      in recovery times. Thus no appreciable recovery was observed from the responses
      to (RS)-salmeterol, whereas a rapid loss of inhibition was observed on stopping
      the infusion of (S)-salmeterol, the time to 50% recovery being 30-35 min. 5.
      These relatively short-lasting effects of salmeterol which are not mediated
      through beta 2-adrenoceptors, contrast with the persistence of the responses
      which are mediated through beta 2-adrenoceptors seen in a variety of tissues, but
      are similar to the rate of dissociation of salmeterol observed from artificial
      membranes. These observations suggest that the sustained agonist activity of
      salmeterol is peculiar to responses mediated by beta 2-adrenoceptors.

PMID- 9138706
TI  - The inhibitory effect of the antipsychotic drug haloperidol on HERG potassium
      channels expressed in Xenopus oocytes.
AB  - 1. The antipsychotic drug haloperidol can induce a marked QT prolongation and
      polymorphic ventricular arrhythmias. In this study, we expressed several cloned
      cardiac K+ channels, including the human ether-a-go-go related gene (HERG)
      channels, in Xenopus oocytes and tested them for their haloperidol sensitivity.
      2. Haloperidol had only little effects on the delayed rectifier channels Kv1.1,
      Kv1.2, Kv1.5 and IsK, the A-type channel Kv1.4 and the inward rectifier channel
      Kir2.1 (inhibition < 6% at 3 microM haloperidol). 3. In contrast, haloperidol
      blocked HERG channels potently with an IC50 value of approximately 1 microM.
      Reduced haloperidol, the primary metabolite of haloperidol, produced a block with
      an IC50 value of 2.6 microM. 4. Haloperidol block was use- and voltage-dependent,
      suggesting that it binds preferentially to either open or inactivated HERG
      channels. As haloperidol increased the degree and rate of HERG inactivation,
      binding to inactivated HERG channels is suggested. 5. The channel mutant HERG
      S631A has been shown to exhibit greatly reduced C-type inactivation which occurs
      only at potentials greater than 0 mV. Haloperidol block of HERG S631A at 0 mV was
      four fold weaker than for HERG wild-type channels. Haloperidol affinity for HERG
      S631A was increased four fold at +40 mV compared to 0 mV. 6. In summary, the data
      suggest that HERG channel blockade is involved in the arrhythmogenic side effects
      of haloperidol. The mechanism of haloperidol block involves binding to
      inactivated HERG channels.

PMID- 9138707
TI  - Mechanism of nitric oxide-induced contraction in the rat isolated small
      intestine.
AB  - 1. The contractile response to nitric oxide (NO) in ral ileal myenteric plexus
      longitudinal muscle strips was pharmacologically analysed. 2. NO (10(-7) M)
      induced only contraction while 10(-6) M NO induced contraction followed by
      relaxation. Methylene blue (up to 10(-4) M) did not affect the NO-induced
      contractions but significantly reduced the relaxation evoked by 10(-6) M NO.
      Administration of 8-bromo-cyclic GMP (10(-6)-10(-4) M) only induced relaxation.
      3. Sodium nitroprusside (SNP; 10(-7)-10(-5) M) induced concentration-dependent
      contractions per se; the contractile response to NO, administered within 10 min
      after SNP, was concentration-dependently reduced. The guanosine 3':5'-cyclic
      monophosphate (cyclic GMP) content of the tissues was not increased during
      contractions with 10(-8) M NO and 10(-6) M SNP; it was increased by a factor of 2
      during contraction with 10(-7) M NO, and by a factor of 12 during relaxation with
      3 x 10(-6) M NO. 4. The NO-induced contractions were not affected by ryanodine (3
      x 10(-5) M) but were concentration-dependently reduced by nifedipine (10(-8)-10(
      7) M) and apamin (3 x 10(-9)-3 x 10(-8) M). 5. These results suggest that cyclic
      GMP is not involved in the NO-induced contraction in the rat small intestine. The
      NO-induced contraction is related to extracellular Ca2+ influx through L-type
      Ca2+ channels, that might be activated in response to the closure of Ca(2+)
      dependent K+ channels.

PMID- 9138708
TI  - Proceedings of the Geoffrey Chisholm Day. Prostate Research in the 21st Century.
      Edinburgh, United Kingdom, 28 June 1996.

PMID- 9138709
TI  - Urachal remnants.
AB  - Although urachal remnants rarely are observed clinically, they often give rise to
      a number of problems such as fatal infection and late malignant changes.
      Therefore, a total assessment of the disease with a particular focus on
      embryology, anatomy, and clinical symptoms, as well as the most advisable
      treatment, is called for. The authors report on 33 previously experienced cases
      and discuss the problems involved in both the diagnosis and treatment of these
      anomalies.

PMID- 9138710
TI  - Omphalomesenteric duct malformations.
AB  - Omphalomesenteric duct malformations comprise a wide spectrum of anatomic
      structures and associated symptoms (or no symptoms). They may range from a
      completely patent omphalomesenteric duct at the umbilicus to a variety of lesser
      remnants including cysts, fibrous cords connecting the umbilicus to the distal
      ileum, granulation tissue at the umbilicus, umbilical hernias, and the famous
      diverticulum of Meckel. Symptoms may involve fecal fistulas at the umbilicus,
      intussusception/prolapse of ileum at the umbilicus, intestinal obstruction from a
      variety of causes, melena and anemia, abdominal pain and inflammation, etc.
      Although symptoms occur most frequently during childhood years (especially in the
      first 2 years of life), they may occur through adult years as well. Although
      these malformations are found with equal frequency among the sexes, a
      significantly greater incidence of symptoms is encountered in males. Although one
      of the very most frequent malformations to be found (Meckel's diverticulum in 2%
      to 3% of the population), they are one of the most unlikely to cause symptoms
      (also Meckel's diverticulum). An awareness of the diversity of these
      malformations in type and symptomotology is essential to their proper and optimal
      management.

PMID- 9138711
TI  - Gastroschisis and omphalocele.
AB  - Infants with omphalocele and gastroschisis represent a challenging group of
      patients. Antenatal diagnosis may affect management by stimulating a search for
      associated anomalies, and by changing the site, mode, or timing of delivery.
      During the neonatal period, great care must be taken to minimize fluid and heat
      loss, and to prevent bowel distension. Although the goal of the surgeon is to
      accomplish abdominal wall closure in a single stage, a number of options exist
      where this is not possible. Other considerations include prevention and control
      of sepsis, nutritional support, respiratory status, and dysfunction of the liver,
      kidneys, and intestine because of increased abdominal pressure. Long-term
      outcome, in the absence of major chromosomal and structural anomalies, is
      excellent.

PMID- 9138712
TI  - Bladder exstrophy.

PMID- 9138713
TI  - Cloacal exstrophy.

PMID- 9138714
TI  - Embryonic development of the ventral body wall and its congenital malformations.
AB  - Congenital abdominal wall defects, frequently associated with other anomalies,
      are found in many forms. Consequently, there is still controversy in the
      literature concerning nomenclature, classification, and pathogenesis. Recently,
      we proposed a new nomenclature and classification of abdominal wall defects based
      on the early development of the umbilical cord and of the ventral body wall.
      According to this classification the complete spectrum of abdominal wall defects,
      including cloacal exstrophy, bladder exstrophy, and epispadias, can be subdivided
      into four types: primary (thoraco-)abdominoschisis, omphalocele, body wall
      dysplasia, and secondary (thoraco-)abdominoschisis. Each type is characterized by
      its specific configuration of the placenta, the membranes, the umbilical cord,
      and the fetus. Anomalies such as urachal remnants and omphalomesenteric duct
      malformations can be explained by disturbances during later stages of umbilical
      cord development.

PMID- 9138715
TI  - Prenatal diagnosis and management of abdominal wall defects.
AB  - The widespread use of fetal ultrasonography in routine antenatal care now allows
      the majority of abdominal wall defects to be identified prenatally, with
      subsequent opportunities for parental counseling, fetal intervention, and optimal
      perinatal management. Outcome is significantly affected by the presence of
      additional structural or chromosomal malformations; appropriate multidisciplinary
      counseling and management is dependent on the early identification of such
      anomalies in addition to accurate delineation of the abdominal wall defect
      itself. In cases with associated lethal or multiple severe abnormalities, parents
      may opt for elective termination of the pregnancy. Serial sonography is of
      particular value in gastroschisis, but there is little evidence that fetal
      manipulation or premature delivery confers any significant benefit. For all types
      of abdominal wall defect, optimal perinatal management is achieved in centers
      where neonatal medical, surgical, and anesthetic expertise is immediately
      available; cases diagnosed in units without these services should be considered
      for in utero transport to the nearest perinatal center.

PMID- 9138716
TI  - Prune-belly syndrome: ongoing controversies regarding pathogenesis and
      management.
AB  - Classical prune-belly syndrome (also known as Triad syndrome, Eagle-Barrett
      syndrome, abdominal muscular deficiency syndrome) consists of a triad of
      anomalies: deficient abdominal wall musculature, urinary tract dilatation, and
      cryptorchidism. Although most investigators consider prune-belly syndrome a
      distinct entity, there is no consensus as to its pathogenesis despite extensive
      study of clinical cases and pathological material. Prognosis may vary from death
      in utero to a near-normal life expectancy. The lack of understanding of
      pathogenesis and wide range of severity result in dilemmas in treatment planning,
      and surgeons vary widely in their approach. This article discusses prune-belly
      syndrome, presents the currently favored hypotheses regarding its pathogenesis,
      and gives an overview of accepted management strategies.

PMID- 9138718
TI  - Drug-free evaluation of rat models of parkinsonism and nigral grafts using a new
      automated rotarod test.
AB  - A variety of tests are available for the evaluation of behavioural deficits in
      rat models of hemiparkinsonism; many, however, are of limited applicability or
      insufficiently objective. The drug-induced turning behaviour test is widely used.
      A disadvantage of this test is that the use of drugs may lead to misleading
      results. Here, we describe a drug-free rotarod test that was used to evaluate the
      effects of unilateral 6-hydroxydopamine lesions, nigral grafts, and subrotational
      doses of apomorphine. The rotarod unit was automated and interfaced to a personal
      computer allowing automatic recording of the time that each rat was able to stay
      on the rod at different rotational speeds (i.e., progressively increasing the
      difficulty of the task). A combination of lesion-induced deficits resembling
      those of Parkinson's disease appears to be involved in falling from the rod. The
      test shows high effectiveness for identifying rats with maximal dopaminergic
      lesions, but is also effective for identifying partial lesions. Rotarod
      performance profiles were useful for investigating the effects of intrastriatal
      nigral grafts, since low rotation speeds revealed differences from lesioned rats
      (i.e., improvements) while higher speeds revealed differences from normal rats
      (i.e., remaining deficits and partial lesions). The test was effective regardless
      of whether rats were trained on the rod before lesion, after lesion, or after
      grafting. Injections of apomorphine (0.0125 and 0.0250 mg/kg) did not induce
      consistent improvements. These results indicate that the rotarod test is a useful
      drug-free procedure for overall evaluation of basic motor abilities in rat models
      of parkinsonism and treatment-induced changes.

PMID- 9138717
TI  - Enhanced phosphorylation of the postsynaptic protein kinase C substrate
      RC3/neurogranin during long-term potentiation.
AB  - Long-term potentiation (LTP) is a sustained strengthening of synaptic connections
      that occurs in the mammalian hippocampus, and is a cellular mechanism likely to
      contribute to memory formation. One question of current interest is whether the
      biochemical mechanisms responsible for the maintenance of LTP have a presynaptic
      or postsynaptic locus. We have determined that the phosphorylation of the
      postsynaptic protein kinase (PKC) substrate RC3/neurogranin is increased in the
      maintenance phase of LTP, and that the induction of this effect is dependent on
      activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. The
      sustained increase in RC3/neurogranin phosphorylation requires ongoing protein
      kinase activity, as application of the protein kinase inhibitor H-7 after LTP
      induction can reverse the increased RC3/neurogranin phosphorylation. Overall,
      these data are evidence for postsynaptic biochemical changes in the maintenance
      of LTP. They also implicate RC3/neurogranin as a downstream effector of PKC
      activity in LTP that could contribute to physiologic expression of LTP.

PMID- 9138719
TI  - Temporal impairment of microcirculatory perfusion following focal cerebral
      ischemia in the spontaneously hypertensive rat.
AB  - Microcirculatory impairments have theoretically been proposed as a potential
      factor in the development of ischemic injury, but few attempts have been made to
      directly assess microvascular patency following stroke. To address this issue we
      investigated the temporal changes in microvascular perfusion induced by permanent
      focal ischemia. Halothane-anesthetized spontaneously hypertensive rats were
      subjected to middle cerebral artery occlusion (MCAO) of 5 min to 4 h duration.
      Two fluorescent tracers (FITC-dextran and Evans blue) were then sequentially
      administered i.v. and allowed to circulate for 10 and 5 s respectively. Tissue
      sections were examined by fluorescent microscopy, and the mean number of perfused
      microvessels/mm2 calculated for cortical areas representing non-ischemic (Region
      A), perifocal/penumbral (Region B) and core ischemic (Region C) regions. For sham
      operated controls, virtually all microvessels perfused with tracer within 5 s. In
      contrast MCAO induced significant reductions in the number of perfused
      microvessels in Regions B and C. The most marked impairments in perfusion were
      observed in core MCA territory (e.g. 2-10% of control values for 5 s circulation
      period) while, initially, the deficit was less severe in penumbral cortex.
      However, a secondary perfusion impairment developed over time in the
      perifocal/penumbral region, so that the deficit was greater 4 h after MCAO than
      at earlier time points (e.g. 72%, 71% and 22% of control value for 0.5, 1 and 4 h
      MCAO respectively; 10 s circulation period). In conclusion, MCAO induced severe
      impairments in microcirculatory perfusion within the core ischemic region, and to
      a lesser extent in the penumbra. However, the development of a more severe
      perfusion deficit in the penumbra within 4 h of MCAO supports the hypothesis that
      microcirculatory failure in this region contributes to its recruitment to the
      ischemic infarct.

PMID- 9138720
TI  - NMDA receptor antagonist blocks the bradycardic but not the pressor response to L
      glutamate microinjected into the nucleus tractus solitarius (NTS) of
      unanesthetized rats.
AB  - In the present study we evaluated the role of NMDA receptors on the pressor and
      bradycardic responses to L-glutamate (L-Glu) microinjected into the nucleus
      tractus solitarius (NTS) of unanesthetized rats. L-Glu (1 nmol/100 nl) was
      microinjected into the NTS before and 10 min after microinjection of
      phosponovaleric acid (AP-5), a selective NMDA receptor antagonist, into the NTS
      of three different groups of rats (0.5, 2.0 and 10.0 nmol/100 nl). Microinjection
      of AP-5 into the NTS produced a dose-dependent reduction in the bradycardic
      response to L-Glu. However, no significant change in the pressor response to L
      Glu was observed. These results indicate that the activation of the cardiovagal
      component (bradycardia) by L-Glu involves NMDA receptors and suggest that the
      activation of the sympatho-excitatory component (pressor response) by L-Glu in
      the commissural NTS is mediated by non-NMDA receptors.

PMID- 9138722
TI  - Somatostatin release as measured by in vivo microdialysis: circadian variation
      and effect of prolonged food deprivation.
AB  - In vivo microdialysis was used to determine SRIF release from the hypothalamus in
      unanesthetized male rats over a period of 24 h and in rats deprived of food for
      72 h, in relation to changes in plasma GH levels. Before the experiment, a
      microdialysis probe was inserted into the anterior pituitary gland of the rats
      with an indwelling right atrial cannula. Dialysates and blood samples were
      collected serially, after normal feeding or 72-h deprivation of food. Normal rats
      implanted with the microdialysis probe showed an episodical pattern of GH
      secretion at intervals of 3 h. SRIF was secreted in a pulsatile fashion in the
      dark period in a similar manner to the light period. Mean SRIF pulse amplitude
      and mean SRIF level were significantly increased in the dark period. There was no
      significant correlation between the SRIF and GH pulses in the light period. SRIF
      levels in dialysates obtained from fed rats and food-deprived rats showed a
      pulsatile pattern. Food deprivation resulted in significant increases in mean
      SRIF level and mean SRIF pulse amplitude. These results suggest that the
      existence of circadian rhythm in SRIF release and the increase in SRIF release
      play an important role in suppressing GH secretion during prolonged food
      deprivation.

PMID- 9138721
TI  - Modulatory role of catecholamines in the transsynaptic expression of c-fos in the
      rat medial prefrontal cortex induced by disinhibition of the mediodorsal
      thalamus: a study employing microdialysis and immunohistochemistry.
AB  - We studied the interaction of catecholaminergic and thalamic afferents of the
      medial prefrontal cortex (PFC) by analyzing the effects of catecholamine
      depletion on thalamus-induced c-fos expression in the PFC of freely moving rats.
      Thalamic projections to the PFC were pharmacologically activated by perfusing the
      GABA-A receptor antagonist bicuculline (0.03 mM or 0.1 mM) through a dialysis
      probe implanted into the mediodorsal thalamic nucleus. Bicuculline perfusion
      induced Fos-like immunoreactivity in the thalamic projection areas, including the
      PFC, and in the thalamic nuclei surrounding the dialysis probe. 6-Hydroxydopamine
      lesions of the ventral tegmental area causing a 70-80% depletion of
      catecholamines in the PFC did not influence the increase in the number of Fos
      like immunoreactive nuclei in the prefrontal cortex in response to thalamic
      stimulation. However, densitometric image analysis revealed that the intensity of
      Fos-like immunoreactivity in the PFC of lesioned rats perfused with 0.1 mM
      bicuculline was higher than in correspondingly treated controls. The behavioral
      activity to bicuculline perfusion, an increase of non-ambulatory activity (0.03
      mM) followed by locomotion and rearing (0.1 mM), was not changed in 6
      hydroxydopamine-lesioned rats. It is suggested that the thalamically induced c
      fos response is directly mediated by excitatory, presumably glutamatergic,
      transmission and not indirectly by an activation of catecholaminergic afferents
      of the PFC. The increase in the intensity of Fos-like immunostaining in strongly
      stimulated, catecholamine-depleted rats suggests that catecholamines modulate the
      degree to which thalamic activity can activate the PFC of awake animals.

PMID- 9138723
TI  - Effect of lanthanum on voltage-dependent gating of a cloned mammalian neuronal
      potassium channel.
AB  - The effect of the trivalent cation lanthanum (La3+) on voltage-dependent gating
      of a cloned mammalian neuronal Kv1.1 potassium channel was studied under whole
      cell voltage-clamp conditions in oocytes of Xenopus laevis. La3+ (100 microM) was
      found to decrease the potassium currents at all test potentials and to shift the
      midpoint of the fraction open channels/membrane voltage curve by approximately
      +20 mV. The opening and closing time constants of Kv1.1 channels were empirically
      fitted with a 4th power Hodgkin-Huxley formalism, or with mono- and multi
      exponentials. It was found that La3+ slowed down the kinetics of activation,
      speeded up those of deactivation, and shifted the opening kinetics by
      approximately + 60 mV. Interestingly, all these parameters of channel gating were
      not affected equally by La3+. Furthermore, amplitudes of the inward tail currents
      evoked at potentials more negative than the potassium equilibrium potential
      (E(K+)) were more strongly inhibited by La3+ than those of the outward tail
      currents evoked at potentials more positive than E(K+). This suggests voltage
      dependent block and binding of La3+ to the Kv1.1 channel protein. We conclude
      that these actions cannot be explained in terms of surface charge considerations
      alone. Our results provide evidence for a direct interaction with the potassium
      channel protein, shedding new light on the mechanism of action of this
      lanthanide.

PMID- 9138724
TI  - Alterations of central noradrenergic transmission in Ts65Dn mouse, a model for
      Down syndrome.
AB  - Mice with segmental trisomy 16 (Ts65Dn) which have triplication of a region of
      mouse chromosome 16 homologous to the Down syndrome critical region in human
      chromosome 21, are used as a model for Down syndrome. Functioning of the central
      beta-noradrenergic transmission was studied in Ts65Dn mice. Binding analysis in
      cerebral cortex revealed no change in the number of beta-adrenoceptors and a
      slight reduction of affinity. The beta-adrenoceptor transduction was assessed by
      analyzing cAMP formation in the cerebral cortex, hippocampus and cerebellar
      cortex under basal conditions and after stimulation with isoprenaline and
      forskolin. Basal production of cAMP was significantly reduced in hippocampus and
      cerebellar cortex of Ts65Dn mice compared to control, but not in cerebellum.
      After phosphodiesterase inhibition, net increments in cAMP accumulation were
      similar in both groups of mice. Stimulation of cAMP production by isoprenaline
      (10 microM) and forskolin (10 microM) was much higher in hippocampus than in
      cerebral cortex of either group. In both areas, but not in cerebellum, the
      stimulatory responses were consistently and significantly smaller in Ts65Dn than
      in control mice. Concentration-response curves for isoprenaline and forskolin
      were generated in the cerebral cortex. Emax responses were lower in trisomic than
      in control mice; however, in Ts65Dn mice the slope of the response curve to
      isoprenaline was markedly depressed whereas that to forskolin was similar to
      control. It is concluded that Ts65Dn mice show severe deficiencies in the
      synaptic transmission of the central beta-noradrenergic system, which are
      selective for specific brain areas.

PMID- 9138725
TI  - Quantitative localization of NMDAR1 receptor subunit immunoreactivity in
      inferotemporal and prefrontal association cortices of monkey and human.
AB  - The cellular and synaptic localization of immunoreactivity for the N-methyl-D
      aspartate (NMDA) receptor subunit, NMDAR1, was investigated in inferotemporal and
      prefrontal association neocortices of monkeys and humans. In all monkey
      association areas examined, the laminar distribution patterns of NMDAR1
      immunoreactivity were similar, and characterized by predominant pyramidal-like
      neuronal labeling in layers II, III, V and VI and a dense neuropil labeling
      consisting of intensely stained puncta and fine-caliber processes present
      throughout layers I-III, and V-VI. Layer IV, in contrast, contained only very
      lightly immunostained neurons which mostly lacked extensive dendritic staining.
      The laminar distribution of NMDAR1 immunolabeling in human association cortex was
      similar to that observed in monkeys. Electron microscopy of monkey areas 46 and
      TE1 confirmed that intensely immunoreactive asymmetrical postsynaptic densities
      were present throughout all cell-dense layers of prefrontal and inferotemporal
      association cortex. Quantitative analyses of the laminar proportions of
      immunoreactive synapses demonstrated that in both areas examined, the percentages
      of immunolabeled synapses were mostly similar across superficial layers, layer IV
      and infragranular layers. Finally, quantitative double-labeling
      immunofluorescence for non-NMDA receptor subunits or calcium-binding proteins
      demonstrated that virtually all GluR2/3 or GluR5/6/7-immunoreactive neurons were
      also labeled for NMDAR1, while regionally-specific subsets of parvalbumin-,
      calbindin- and calretinin-immunoreactive neurons were co-labeled. These data
      indicate that in primate association cortex, NMDA receptors are heterogeneously
      distributed to subsets of functionally distinct types of neurons and subsets of
      excitatory synapses, suggesting a critical and highly specific role in mediating
      the activity of excitatory connectivity which converges on cortical association
      areas.

PMID- 9138726
TI  - Mouse cerebellar adenosinergic modulation of ethanol-induced motor
      incoordination: possible involvement of cAMP.
AB  - As an extension of our previous work pertaining to brain adenosinergic modulation
      of ethanol-induced motor incoordination, the effect of direct intracerebellar
      administration of the A1-selective adenosine agonist, N6-cyclohexyladenosine
      (CHA) on ethanol-induced motor incoordination was evaluated. Marked accentuation
      of ethanol-induced motor impairment by CHA was observed. No change in the normal
      motor coordination was noted when CHA administration was followed by saline
      instead of ethanol. Intracerebellar cAMP or its analog, 8-(4-chlorophenylthio)
      cAMP, significantly inhibited ethanol's motor impairment in a dose-related manner
      as well as abolished CHA's accentuating effect on ethanol-induced motor
      incoordination. These observations suggested a possible involvement of cAMP in
      the adenosinergic modulation and in the expression of ethanol-induced motor
      incoordination. Further support was provided by the observation of a marked
      accentuation and attenuation in a dose-related manner of ethanol-induced motor
      impairment as well as CHA's accentuation of ethanol's motor impairment by
      intracerebellar miconazole and forskolin, respectively. However, equimolar
      intracerebellar doses of miconazole and forskolin (inhibitor and stimulator of
      adenylyl cyclase, respectively) failed to significantly alter ethanol-induced
      motor incoordination probably due to their mutual functional antagonism. The
      expression of adenosinergic modulation and that of ethanol-induced motor
      impairment most likely involved Gi protein-coupled receptor(s) (such as adenosine
      receptors). The involvement of receptors linked to pertussis toxin-sensitive G
      proteins was suggested because intracerebellar pertussis toxin pretreatment
      markedly inhibited ethanol-induced motor incoordination as well as CHA's
      accentuation of ethanol's motor impairment. Finally, cAMP, unlike its antagonism
      to CHA's accentuation, failed to antagonize the accentuation of ethanol-induced
      motor impairment by intracerebellar GABA(A) agonist (+)-muscimol. This indicated
      selectivity of cAMP participation in G protein coupled receptor (such as
      adenosine)-mediated response and not in ionic channel coupled receptor (such as
      GABA(A))-mediated mechanism. Overall, the data suggested a possible involvement
      of cerebellar adenylyl cyclase-cAMP signalling pathway in the adenosinergic
      modulation of ethanol's ataxia.

PMID- 9138727
TI  - The effects of behavioral tasks on the in vitro phosphorylation of intermediate
      filament subunits of rat hippocampus are mediated by CaMKII and PKA.
AB  - Neurofilaments (NF) are the most abundant constituents of the neuronal
      cytoskeleton, while glial fibrillary acidic protein (GFAP) is a major component
      of the glial astrocyte cytoskeleton. These proteins can be phosphorylated by
      different protein kinases and they are regulated in a complex way by
      phosphorylation. Using a hippocampal cytoskeletal fraction we demonstrated that
      the behavioral tasks of inhibitory avoidance and habituation can differently
      alter the in vitro phosphorylation of the 150 kDa (NF-M) and the 68 kDa (NF-L)
      neurofilament subunits and of the GFAP. In order to verify the effect of
      habituation and inhibitory avoidance training on the phosphatase activity, we
      performed the time course-dephosphorylation assay (5-30 min of incubation of the
      cytoskeletal fraction with 32P-ATP). Subsequently we investigated the effect of
      these behavioral tasks on the protein kinase activities associated with the
      cytoskeletal fraction, carring out the 32P incorporation assays in the presence
      of specific kinase inhibitors. Results suggest that phosphatase activity is not
      altered in the cytoskeletal fraction by the behavioral tasks and that the
      increased in vitro phosphorylation of NF-M and NF-L caused by habituation is
      probably mediated by the Ca2+/calmodulin dependent protein kinase (CaMKII).
      However, the inhibition of GFAP in vitro phosphorylation caused by inhibitory
      avoidance training is probably related to the cAMP dependent protein kinase
      (PKA).

PMID- 9138728
TI  - Somatostatin and brain-derived neurotrophic factor mRNA expression in the primate
      brain: decreased levels of mRNAs during aging.
AB  - The expression of the genes for somatostatin (SRIF) and brain-derived
      neurotrophic factor (BDNF) was investigated in the central nervous system (CNS)
      of the macaque monkey (Macaca fuscata fuscata). Using Northern blot analysis, one
      SRIF mRNA transcript, 0.65 kb, and two BDNF mRNA transcripts, 1.6 and 4.0 kb in
      length, were detected in the monkey brain tissues. During the aging process (2
      years, 10 years, and > 30 years), the ratio of SRIF mRNA/glyceraldehyde-3
      phosphate dehydrogenase (G3PDH) mRNA significantly decreased (60-70%) in the
      hippocampus and in several cerebral subdivisions such as frontal cortex, temporal
      cortex, motor cortex, somatosensory cortex and visual cortex. BDNF mRNA was
      expressed in the various cerebral subdivisions and in the hippocampus. During the
      aging process, the gene expression of BDNF declined (20-50% for the 4.0 kb
      transcript, and 40-70% for the 1.6 kb transcript) in the various cerebral
      subdivisions. In the hippocampus, the level of the 1.6 kb mRNA at > 30 years old
      declined to 60% of the level at 2 years old, while the 4.0 kb mRNA did not change
      significantly during the aging process. Recent studies have shown that BDNF
      enhances the expression of SRIF mRNA in the rodent cerebral cortex (Nawa, H. et
      al., J. Neurochem., 60 (1993) 772-775; Nawa, H. et al., J. Neurosci., 14 (1994)
      3751-3765). These studies and our present results suggest that the decrease in
      gene expression for a neurotrophic molecule, such as BDNF, might cause the levels
      of SRIF mRNA to decline in the primate brain during the aging process.

PMID- 9138729
TI  - Amantadine: an antiparkinsonian agent inhibits bovine brain 60 kDa calmodulin
      dependent cyclic nucleotide phosphodiesterase isozyme.
AB  - The effect of amantadine (an antiparkinsonian agent) on calmodulin-dependent
      cyclic nucleotide phosphodiesterase isozymes was investigated. Amantadine
      inhibited bovine brain 60 kDa calmodulin-dependent cyclic nucleotide
      phosphodiesterase but not the bovine brain 63 kDa, heart and lung calmodulin
      dependent cyclic nucleotide phosphodiesterase isozymes. The inhibition of bovine
      brain 60 kDa calmodulin-dependent cyclic nucleotide phosphodiesterase was
      overcome by increasing the concentration of calmodulin. This suggests that
      amantadine may be an antagonist of calmodulin or act specifically and reversibly
      on the action of calmodulin. The bovine brain 60 kDa calmodulin-dependent cyclic
      nucleotide phosphodiesterase isozyme is predominantly expressed in the brain and
      its inhibition may result in increased intracellular levels of cyclic AMP (cAMP).
      The increased intracellular levels of cAMP have a protective role for
      dopaminergic neurons. The present findings suggest that amantadine may be a
      valuable tool to investigate the physiological role of 60 kDa calmodulin
      dependent cyclic nucleotide phosphodiesterase isozyme in the progression of
      Parkinson's disease and gives a new insight into the action of this drug.

PMID- 9138730
TI  - Involvement of cholinergic neurons in the release of dopamine elicited by
      stimulation of mu-opioid receptors in striatum.
AB  - The involvement of striatal cholinergic neurons in the release of dopamine (DA)
      elicited by the mu-opioid receptor agonist DAGO ([D-Ala2, NMePhe4
      Gly5(ol)]enkephalin) was explored. The striatal release of DA was measured by
      microdialysis in rats anesthetized with chloral hydrate. When infused in the
      striatum, through the microdialysis probe, DAGO increased the extracellular
      levels of DA. The previous injection in striatum of AF 64-A, a toxin for
      cholinergic neurons, or the concomitant infusion of the M2-muscarinic antagonist
      methoctramine abolished the effect of DAGO on the DA release. It is concluded
      that stimulation of mu-opioid receptors, by inhibiting the acetylcholine release
      which stimulates tonically M2-muscarinic receptors likely associated with
      dopaminergic nerve endings, indirectly increases the striatal DA release.

PMID- 9138731
TI  - Glycine-immunoreactive terminals in the rat trigeminal motor nucleus: light- and
      electron-microscopic analysis of their relationships with motoneurones and with
      GABA-immunoreactive terminals.
AB  - Post-embedding immunolabelling methods were applied to semi-thin and ultrathin
      resin sections to examine the relationships between glycine- and gamma
      aminobutyric acid (GABA)-immunoreactive terminals on trigeminal motoneurones,
      which were identified by the retrograde transport of horseradish peroxidase
      injected into the jaw-closer muscles. Serial sections were cut through boutons
      and alternate sections were incubated with antibodies to glycine and GABA. Light
      microscopic analysis of semi-thin sections revealed a similar pattern of glycine
      and GABA-immunoreactive boutons along the motoneurone soma and proximal
      dendrites, and of immunoreactive cell bodies in the parvocellular reticular and
      peritrigeminal areas surrounding the motor nucleus. Immunoreactive synaptic
      terminals on motoneurones were identified on serial ultrathin sections at
      electron-microscopic level using a quantitative immunogold method. Three
      populations of immunolabelled boutons were recognized: boutons immunoreactive for
      glycine alone (32%), boutons immunoreactive for GABA alone (22%), and boutons
      showing co-existence of glycine and GABA immunoreactivities (46%). Terminals
      which were immunoreactive for glycine only contained a higher proportion of
      flattened synaptic vesicles than those which were immunoreactive for GABA only,
      which contained predominantly spherical vesicles. Terminals which exhibited both
      immunoreactivities contained a mixture of vesicle types. All three classes of
      terminal formed axo-dendritic and axo-somatic contacts onto retrogradely labelled
      motoneurones. A relatively high proportion (25%) of boutons that were
      immunoreactive for both transmitters formed synapses on somatic spines. However,
      only GABA-immunoreactive boutons formed the presynaptic elements at axo-axonic
      contacts: none of these were found to contain glycine immunoreactivity. These
      data provide ultrastructural evidence for the role of glycine and GABA as
      inhibitory neurotransmitters at synapses onto jaw-closer motoneurones, but
      suggest that presynaptic control of transmission at excitatory (glutamatergic)
      synapses on motoneurones involves GABAergic, but not glycinergic inhibition.

PMID- 9138732
TI  - Effects of extensor muscle afferents on the timing of locomotor activity during
      walking in adult rats.
AB  - The influence of hind leg extensor muscle afferents on the timing of locomotor
      phase transitions was examined in adult, decerebrate rats, walking on a
      treadwheel. Walking occurred either spontaneously or was induced by stimulation
      of the mesencephalic locomotor region. Large diameter muscle afferents
      innervating the lateral or medial gastrocnemius were electrically stimulated
      during walking. A stimulus was delivered either at the onset of extensor muscle
      activity, or randomly during the step cycle. Stimulation with a train duration of
      300 ms at the onset of extension increased the duration of the extensor bursts.
      The subsequent flexion phase was delayed. Stimulation with a shorter stimulus
      train (150 ms) early in extension had little effect on the extension phase
      duration. However when delivered at the end of extension the same stimulus
      significantly increased the duration of the extension phase and decreased the
      duration of the following flexion phase. Stimulating near the end of the flexion
      phase delayed onset and decreased duration of the subsequent extension phase. The
      effects of stimulating extensor afferents during the extension phase were weaker
      but qualitatively similar, to those in cats, suggesting similar mechanisms. The
      results of this study also show major differences in the integration of extensor
      muscle afferents between adult and neonatal rats.

PMID- 9138733
TI  - Expression of activating transcription factor-2 (ATF-2), one of the cyclic AMP
      response element (CRE) binding proteins, in Alzheimer disease and non
      neurological brain tissues.
AB  - Cyclic AMP response element (CRE) is a specific DNA sequence which mediates
      transcriptional activation in the response to the cyclic AMP-activated and
      protein kinase A dependent signaling pathway. We examined the localization of one
      of the CRE binding proteins which is preferentially expressed in the brain,
      activating transcription factor-2 (ATF-2), by immunohistochemistry and
      Southwestern histochemistry, using the brains of neurologically normal and
      Alzheimer disease (AD) cases. In all brains, the anti-ATF-2 antibody stained
      white matter microglial cells. In AD, the cytoplasm of some cortical neurons was
      also positively stained, but no such staining was seen in the neocortex in non
      neurological cases staining. However, both the nuclei and cytoplasm of some
      hippocampal neurons were positive in non-neurological brain tissues. In AD,
      except for severely damaged areas such as CA1, positive neuronal staining was
      seen. Southwestern histochemistry gave the same results as immunohistochemistry.
      These data suggest that the localization of ATF-2 in cortical neurons in AD may
      reflect early pathological changes characteristic of AD, and that these
      histochemistrical methods may allow one to differentiate between healthy and
      mildly damaged neurons.

PMID- 9138735
TI  - Evidence for roles of kappa-opioid and NMDA receptors in the mechanism of action
      of ibogaine.
AB  - Ibogaine, a putatively anti-addictive alkaloid, binds to kappa-opioid and NMDA
      receptors. In the present study we investigated the roles of kappa-opioid and
      NMDA actions in mediating ibogaine's (40 mg/kg, i.p.) behavioral and
      neurochemical effects in rats. A combination of a kappa-opioid antagonist
      (norbinaltorphimine, 10 mg/kg, s.c.) and a NMDA agonist (NMDA, 20 mg/kg, i.p.)
      partially prevented ibogaine-induced inhibition of intravenous morphine self
      administration and ibogaine-induced antagonism of morphine-induced locomotor
      stimulation. The combination, as well as norbinaltorphimine and NMDA alone,
      blocked the acute effects of ibogaine on dopamine release and metabolism in the
      striatum. The data suggest that both kappa-opioid agonist and NMDA antagonist
      actions of ibogaine contribute to its putative anti-addictive effects.

PMID- 9138734
TI  - Activation of phosphatidylcholine-selective phospholipase C by I1-imidazoline
      receptors in PC12 cells and rostral ventrolateral medulla.
AB  - The I1-imidazoline receptor is expressed in the rostral ventrolateral medulla
      (RVLM) where it mediates vasodepression, and in PC12 pheochromocytoma cells where
      it elicits generation of diacylglycerol independent of phosphatidylinositol
      turnover or activation of phospholipase D. We hypothesized that the I1
      imidazoline receptor couples to a phosphatidylcholine-selective phospholipase C
      (PC-PLC). The I1-agonist moxonidine elicited diacyglyceride accumulation and
      release of [3H]phosphocholine from PC12 cells prelabeled with [3H]choline. The PC
      PLC inhibitor D609 abolished both responses. Microinjection of D609 into the RVLM
      of hypertensive rats blocked the vasodepressor response to intravenous
      moxonidine. These data implicate PC-PLC in cellular and organismic responses to
      I1-receptor stimulation.

PMID- 9138736
TI  - In the mouse, the corticoid stress response depends on lateralization.
AB  - The influence of brain/behavioral lateralization on the neuroendocrine stress
      response was studied in the mouse. Using a paw preference test in a food reaching
      task, mice were classified as left-pawed, ambidextrous or right-pawed. Plasma
      levels of corticosterone (CS) were measured in basal conditions, 4 h after an
      intraperitoneal injection of lipopolysaccharide (LPS) or after a short period of
      restraint. In unstressed control mice, plasma levels of corticosterone were
      higher in left-pawed animals as compared to ambidextrous. LPS increased plasma
      levels of CS to similarly high levels, around 600 ng/ml, in the three
      experimental groups. By contrast after 1 h of restraint, the increased CS levels,
      lower to those observed after LPS injection, were higher in left-pawed mice as
      compared to right-pawed animals. These results are the first demonstration that
      activation of the hypothalamic-pituitary-adrenal axis observed during the stress
      response to a physical stimulus may be related to lateralization.

PMID- 9138737
TI  - Modification of the binding of [3H]MK-801 to brain regions and spinal cord of
      rats treated chronically with U-50,488H, a kappa-opioid receptor agonist.
AB  - Male Sprague-Dawley rats were rendered tolerant to U-50,488H by twice-daily
      injections of the drug (25 mg/kg, i.p.) for 4 days. In tolerant rats, the binding
      of [3H]MK-801 was increased in pons and medulla and corpus striatum but decreased
      in midbrain and hippocampus and was due to changes in Bmax values. In U-50,488H
      abstinent rats, the binding of [3H]MK-801 was increased in pons and medulla and
      hippocampus, and decreased in midbrain and amygdala. In hippocampus, the Bmax of
      [3H]MK-801 was increased but the Kd was decreased whereas in amygdala and pons
      and medulla, the changes were due to alterations in the Bmax values. Previous
      studies have shown that NMDA receptor antagonists block the tolerance to the
      analgesic action of U-50,488H in rodents. The present studies demonstrate
      differential changes in the NMDA receptors of brain regions of U-50,488H-tolerant
      and -abstinent rats.

PMID- 9138738
TI  - N(G)-nitro-L-arginine reverses L-arginine induced changes in morphine
      antinociception and distribution of morphine in brain regions and spinal cord of
      the mouse.
AB  - Twice daily injections of L-arginine (200 mg/kg, i.p.), a precursor for nitric
      oxide (NO), for 4 days decreased morphine antinociception in male Swiss-Webster
      mice. Chronic treatment with L-arginine also produced significant decreases in
      morphine levels in midbrain, pons and medulla, hippocampus, corpus striatum and
      spinal cord of mice following an injection of morphine (10 mg/kg, s.c.) in
      comparison to vehicle-injected mice. N(G)-nitro-L-arginine (L-NNA), an inhibitor
      of NO synthase (NOS), (5 mg/kg, i.p.) given prior to each injection of L-arginine
      reversed the effects of the latter on morphine antinociception and decreases in
      morphine levels in brain regions and spinal cord. Chronic injections of L-NNA
      alone did not modify either morphine antinociception or morphine distribution in
      brain regions and spinal cord of mice. These results suggest that decreases in
      morphine antinociception by chronic treatment with L-arginine is related to the
      decreases in the entry of morphine in the central sites. The reversal of L
      arginine-induced effects by L-NNA suggests that NO-NOS system may be playing a
      critical role in the regulation of blood-brain barrier to morphine.

PMID- 9138739
TI  - Biphasic alteration in the trigeminal nociceptive neuronal responses after
      intracerebroventricular injection of prostaglandin E2 in rats.
AB  - To investigate the role of prostaglandin E2 (PGE2) in the brain in nociception
      electrophysiologically, we injected PGE2 (0.1 fmol(-1) nmol) into the lateral
      cerebroventricle (LCV) of anesthetized rats and observed the changes of the
      responses of the wide dynamic range (WDR) neurons in the trigeminal nucleus
      caudalis to noxious pinching of facial skin. The LCV injection of PGE2 at 1 fmol
      and 10 fmol enhanced the responses of the majority of WDR neurons to noxious
      stimuli, whereas that of PGE2 at 100 pmol and 1 nmol suppressed them. The
      enhancement and suppression of the nociceptive responses of WDR neurons were
      observed 15-25 min and 5-15 min after injection of PGE2 at 10 fmol (3.53 pg) and
      1 nmol (353 ng), respectively. On the other hand, the LCV injection of PGE2 at
      both 10 fmol and 1 nmol had no effect on the responses of the low threshold
      mechanoreceptive neurons to skin brushing. These results provide
      electrophysiological evidence that brain-derived PGE2 has biphasic effects on
      nociception, i.e., it induces mechanical hyperalgesia at lower doses and
      hypoalgesia at higher doses in rats.

PMID- 9138740
TI  - Expression of mRNA for brain-derived neurotrophic factor in the dorsal root
      ganglion following peripheral inflammation.
AB  - It is well known that the nerve growth factor (NGF) may serve as a link between
      inflammation and hyperalgesia. Recent experiments showed that systemic injection
      of NGF dramatically stimulated the expression of brain-derived neurotrophic
      factor (BDNF) mRNA in the dorsal root ganglion (DRG). In the present study, we
      evaluated the change of BDNF mRNA in the DRG following peripheral inflammation
      and also observed colocalization of BDNF and trkA mRNAs by means of in situ
      hybridization histochemistry in rats. Peripheral tissue inflammation produced by
      an intraplantar injection of Freund's adjuvant into the paws significantly
      increased BDNF mRNA levels in the DRG and many neurons expressing trkA mRNA
      showed increased expession of BDNF mRNA. Intraplantar injection of antibody to
      NGF together with Freund's adjuvant prevented the increase in BDNF mRNA. These
      findings suggest that peripheral inflammation induces an increased expression of
      BDNF mRNA which is mediated by NGF in DRG.

PMID- 9138741
TI  - Transneuronal transport of intracellularly injected biotinamide in primary
      afferent axons.
AB  - Transneuronal transport of biotinamide was observed following intracellular
      injection of biotinamide into rat jaw-muscle spindle afferent axons.
      Microelectrodes were advanced into the mesencephalic nucleus of the trigeminal
      nerve where jaw-muscle spindle afferent axons were identified by their increased
      firing during stretching of the jaw-elevator muscles. Biotinamide (Neurobiotin)
      was then injected into individual axons and the animals were maintained under
      anesthesia for 2-6 h. The animals were then killed via an overdose of anesthetic
      and the brainstem was processed histochemically. Biotinamide-filled axon
      collaterals and terminals were readily visible in the trigeminal motor nucleus,
      the trigeminal sensory nuclei, and adjacent reticular formation. In addition to
      these intracellularly stained axons, two to five neurons per animal (total of 36
      in eight rats) were observed with a homogeneous gray reaction product distributed
      throughout their somata, proximal, and secondary dendrites. These neurons ranged
      in size from small (8-20 mu m, n - 26) to medium-sized (<30 mu m, n = 10) and
      were closely apposed by numerous (up to 20) biotinamide-stained spindle afferent
      boutons. Most of these neurons (n = 22) were located in the dorsomedial portion
      of the spinal trigeminal subnucleus interpolaris (Vi) 2.5-4.5 mm caudal to the
      intra-axonal injection site. Electron microscopic analysis in two rats suggests
      that the transneuronal biotinamide labeling occurred predominantly through
      asymmetric, axodendritic synapses between biotinamide-filled axon terminals and
      Vi neuronal dendrites. Although recent in vitro studies have reported that
      biotinamide permeates through gap junctions, in this study we found no evidence
      of biotinamide traversing the gap junctions which exist between trigeminal
      mesencephalic nucleus (Vme) neuronal somata. These results demonstrate that
      biotinamide can occasionally be transneuronally transported presumably via
      synapses; further information is needed to explain the seemingly sporadic nature
      of this transport.

PMID- 9138742
TI  - Distribution of substance P and calcitonin gene-related peptide immunoreactive
      nerve fibers in the trachea of chronically hypoxic rats.
AB  - The distribution of substance P and calcitonin gene-related peptide
      immunoreactive nerve fibers in the trachea was compared between normoxic and
      chronically hypoxic rats (at 380 mm Hg for 10 weeks). In the normoxic trachea,
      the immunoreactivity to either peptide was seen in the nerve fibers in four
      principal locations: a) within and b) under the ciliated epithelium, c) within
      the smooth muscle bundles in the posterior wall, and d) in the connective tissue
      and around blood vessels in the lamina propria and submucosa. These
      immunoreactive fibers within the epithelium and smooth muscle bundles, in the
      connective tissue, and around blood vessels were thin and displayed some
      varicosities, and those under the epithelium appeared as thick nerve bundles.
      When the distribution and density of immunoreactive fibers were compared between
      normoxic and chronically hypoxic tracheas, there was a difference in number of
      substance P and calcitonin gene-related peptide immunoreactive fibers penetrating
      into the epithelium, although there was no difference in the other three
      locations. The mean number of substance P and calcitonin gene-related peptide
      immunoreactive intraepithelial fibers per section of the chronically hypoxic
      trachea was significantly increased. Because substance P and calcitonin gene
      related peptide are predominant signal peptides of primary sensory neurons, the
      increase of substance P and calcitonin gene-related peptide immunoreactive fibers
      suggests that altered airway reflexes may be a feature of hypoxic adaptation.

PMID- 9138743
TI  - The lazaroid U-83836E improves the survival of rat embryonic mesencephalic tissue
      stored at 4 degrees C and subsequently used for cultures or intracerebral
      transplantation.
AB  - We assessed the effects of addition of the lazaroid U-83836E to a preservation
      medium on the survival of rat dopamine neurons stored before culturing or
      intracerebral transplantation. Embryonic ventral mesencephalic tissue was
      preserved at 4 degrees C for 8 days with or without the addition of 0.3 mu M of U
      83836E to a chemically defined "hibernation" medium. Freshly dissected
      mesencephalic tissue was used in control groups. For culture experiments, the
      mesencephalic tissue was dissociated and grown in serum-containing medium.
      Following 24-48 h in vitro, the number of dopamine neurons in cultures derived
      from tissue hibernated without the lazaroid was 40% of fresh control, compared
      with 67% of control in cultures prepared from tissue stored in the presence of U
      83836E. When mesencephalic tissue was transplanted to the dopamine-depleted
      striatum of hemiparkinsonian rats following 8 days storage at 4 degrees C in a
      medium without U-83836E, the mean number of surviving dopamine neurons in the
      grafts was significantly reduced to 40% of control. In contrast, grafts of tissue
      which had been hibernated in U-83836E-containing medium contained as many
      dopamine neurons as transplants of freshly dissected tissue. High yields of
      surviving grafted dopamine neurons were correlated to a significantly faster
      onset of functional recovery of amphetamine-induced motor asymmetry. We conclude
      that the storage period for rat mesencephalic tissue can be prolonged up to 8
      days when using lazaroid-supplemented hibernation medium. As lazaroids have
      undergone clinical safety testing, the application of lazaroids for tissue
      storage in clinical transplantation trials can be envisaged.

PMID- 9138744
TI  - Acute methamphetamine-induced zif/268, preprodynorphin, and preproenkephalin mRNA
      expression in rat striatum depends on activation of NMDA and kainate/AMPA
      receptors.
AB  - This study tested the role of N-methyl-D-aspartate and kainate/AMPA receptors in
      mediating mRNA expression of the immediate early gene zif/268 and the opioid
      peptide genes preprodynorphin and preproenkephalin in rat forebrain following a
      single injection of methamphetamine. At 3 h after acute methamphetamine [4 mg/kg,
      intraperitoneally (IP)], quantitative in situ hybridization histochemistry
      revealed that zif/268 mRNA expression was increased in the dorsal striatum
      (caudoputamen) and in the sensory cortex. Preprodynorphin was increased in both
      dorsal and ventral striatum (nucleus accumbens) and preproenkephalin was
      increased in the dorsal striatum. Pretreatment with (+ or -)-3-(2
      carboxypiperazin-4-yl)-propyl-1 -phosphonic acid (CPP) (10 mg/kg, IP), an N
      methyl-D-aspartate receptor antagonist, blocked the methamphetamine-induced
      zif/268 mRNA expression in the striatum and in the region of sensory cortex
      representing the upper limb and nose. 6,7-Dinitro-quinoxaline-2,3-dione (DNQX)
      (100 mg/kg, IP), a kainate/AMPA receptor antagonist, did not reduce the ability
      of methamphetamine to induce zif/268 mRNA in striatal and cortical neurons.
      Furthermore, both antagonists caused a parallel blockade of methamphetamine
      stimulated preprodynorphin mRNA expression in the dorsal and ventral striatum but
      did not significantly affect methamphetamine-stimulated preproenkephalin mRNA
      expression. CPP and DNQX reduced basal levels of zif/268 mRNA in cortical and
      striatal neurons but did not affect the constitutive expression of the two opioid
      mRNAs in the striatum. Neither antagonist had a significant effect on
      methamphetamine-induced hyperlocomotion and stereotypies. These results
      demonstrate that both N-methyl-D-aspartate and kainate/AMPA receptor-mediated
      glutamatergic transmission is linked to modulation of the methamphetamine
      stimulated oploid peptide gene expression in rat forebrain. Furthermore, N-methyl
      D-aspartate receptors participate in methamphetamine-stimulated zif/268
      expression.

PMID- 9138745
TI  - Effects of sigma ligands on the ability of rimcazole to inhibit PCP hsp70
      induction.
AB  - Phencyclidine (PCP) can result in schizophrenia-like behavior. It binds at the
      PCP site on the NMDA-receptor calcium channel and at the sigma receptor. PCP also
      induces the heat shock gene hsp7O in retrosplenial cortex neurons. An
      antipsychotic drug, rimcazole, inhibits PCP hsp7O induction. Rimcazole binds
      predominantly to sigma-2 sites. It is hypothesized that sigma ligands without
      antipsychotic properties and with some sigma-2 affinity should partially reverse
      the effects of rimcazole. (+)-3-PPP, (+)-cyclazocine, and (+)-pentazocine bind
      predominantly to sigma-I sites. (+)-3-PPP is also a modest sigma-2 ligand. Female
      Sprague-Dawley rats (200-260 g) were injected intraperitoneally (IP) with (+)-3
      PPP (50 mg/kg), rimcazole (60 mg/kg) and, after 5 min, with PCP (40 mg/kg).
      Brains were sectioned (100 mu m) and presence of the hsp7O gene protein product,
      HSP7O, was determined immunocytochemically. (+)-3-PPP significantly (0 <0.05)
      diminished the ability of rimcazole to inhibit PCP hsp7O induction in the
      retrosplenial cortex. (+)-Cyclazocine (15mg/kg, IP) and (+)-pentazocine (8Omg/kg,
      IP) given in an analogous manner did not diminish the ability of rimcazole to
      inhibit PCP hsp7O induction.

PMID- 9138746
TI  - Validation of a rodent model of Parkinson's Disease: evidence of a therapeutic
      window for oral Sinemet.
AB  - Behavioral measures of parkinsonism that are more clinically relevant than
      rotometry have been developed for rats with severe unilateral dopamine
      depletions, and the validity of these measures is supported by reports that these
      parkinsonian symptoms are attenuated by drugs that are effective in the clinical
      setting. Although the therapeutic gold standard, L-DOPA:carbidopa (Sinemet),
      effectively attenuates parkinsonian symptoms, the beneficial effects of this drug
      are limited by the dyskinesias that it produces at higher doses. The range of
      effective doses, from the minimum dose that produces beneficial effects to the
      dose that produces intolerable dyskinesias, is referred to as the "therapeutic
      window." It would be extremely valuable to assess, preclinically, the effects of
      novel treatments on the therapeutic window for Sinemet. The results of the
      present study support the validity of nondrug-induced measures of parkinsonian
      symptoms in dopamine-depleted rats. Neurological measures revealed large
      behavioral deficits in the affected forelimb analogous to the deficits exhibited
      in Parkinson's disease patients, and these deficits were significantly attenuated
      with some doses of oral Sinemet (30-40 mg/kg). These drug effects on measures of
      parkinsonism were specific to performance with the affected limb. At slightly
      higher doses (50 mg/ kg), the rats were untestable due to severe dyskinesias. The
      results of the present study suggest that it is possible to investigate the
      therapeutic potential of novel treatments as well as their effects on the
      therapeutic window of oral Sinemet in this rodent model of Parkinson's disease.

PMID- 9138747
TI  - Sleep/waking effects following intrathecal administration of the 5-HT(1A) Agonist
      8-OH-DPAT alone and in combination with the putative 5-HT(1A) antagonist NAN-190
      in rats.
AB  - Sleep, waking, and EEG power spectra were investigated in rats after intrathecal
      (IT) administration of a 5-HT(1A) agonist and a 5-HT(1A) antagonist. Total slow
      wave sleep (TSWS) was increased and waking was decreased over the 8-h recording
      period after the 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH
      DPAT) (38 nmol). Within TSWS, SWS1 was unchanged while SWS-2 tended to be
      increased. The 5-HT(1A) antagonist 1-[2-Methoxyphenyl)-4-(4-(2-phthalimido)
      butyl]piperazine hydrobromide (NAN-190) did not change any sleep/waking stages.
      Combined treatment with 8-OH-DPAT and NAN-190 increased variance. Following the
      combination, sleep and waking were not significantly different from control. SWS
      2 tended to be reduced compared to the effect of 8-OH-DPAT alone. There were no
      systematic changes in neither waking nor TSWS fronto-frontal or fronto-parietal
      EEG power spectrum after any of the treatments, indicating that sleep quality was
      not changed. The results confirm earlier data suggesting that in the spinal cord,
      stimulation of 5-HT(1A) receptors have a dampening effect on transmission of
      sensory information, leading to deactivation and thereby increased sleep
      tendency. The reason why the 8-OH-DPAT effect was not clearly antagonized by the
      putative 5-HT1A antagonist NAN-190, may be due to the generally weak antagonistic
      and also partial agonistic effect of NAN-190 as reported in the literature.

PMID- 9138748
TI  - Interaction of cholecystokinin and glutamate agonists within the dLGN, the
      dentate gyrus, and the hippocampus.
AB  - The interaction of sulfated cholecystokinin (CCK-8S) with excitatory amino acids
      (EAA) was studied on single units of the dorsal lateral geniculate nucleus
      (dLGN), the dentate gyrus, and the hippocampal CA3 region in rats anaesthetized
      with urethane. lontophoretic co-administration of small, individually ineffective
      currents of CCK-8S and kainic acid or N-methyl-D-aspartate repeatedly elicited an
      increase of the discharge rate in nearly all geniculate and half of the dentate
      neurons but not in those of the CA3 region. The effect could be reduced by the
      CCKB receptor antagonist PD 135,158 more often than by the CCKA antagonist KL
      1001. The increased firing due to co-administration of CCK and kainate could also
      be suppressed by the non-NMDA antagonist CNQX but not by the NMDA antagonists CPP
      or AP-5, which were otherwise able to prevent the neuron from responding to co
      administration of CCK and NMDA. It is suggested that in distinct brain regions
      the effectivity of the "low level" EAA transmission may be enhanced by small
      amounts of CCK-8S. This is thought to be mediated by a coactivation of CCK and
      EEA receptors.

PMID- 9138749
TI  - Hypothalamic prostaglandin E2 during lipopolysaccharide-induced fever in guinea
      pigs.
AB  - Prostaglandin E2 (PGE2) is postulated to be a central mediator of fever. It is
      generally believed that it is produced in the preoptic area of the anterior
      hypothalamus (POA) because, among other evidence, its level increases both in the
      third ventricle and in the POA in response to pyrogens. However, lately, the
      question has arisen whether PGE2 might, in fact, be formed outside of the brain
      substance and then penetrate it, in particular through the organum vasculosum
      laminae terminalis. If produced outside the brain substance, the peripheral
      blockade of its synthesis should prevent lipopolysaccharides (LPS)-induced fever,
      whereas the intracarotid infusion of PGE2 should produce an increase in core
      temperature (T(C)) as well as in preoptic PGE2. To verify this hypothesis,
      continuous measurements of T(C) and preoptic PGE2 levels were made in conscious
      guinea pigs administered the PGE2 synthase inhibitor, indomethacin (10 or 50
      mg/kg, im) 30 min before S. enteritidis LPS (2 mu g/kg, iv) or before PGE2
      microdialyzed into the POA (1 mu g/mu l at 2 mu g/min for 2.5 h) and during PGE2
      infused into a carotid artery (1 mu g and 10 mu g/mu l at 2 mu g/min for 1 h).
      LPS induced a biphasic 1.4 degrees C fever that was consistently associated with
      an increase in the level of PGE2 in the POA. Indomethacin at 10 mg/kg attenuated
      the course of the LPS-induced fever and prevented the associated increase in
      preoptic PGE2 for 90 min after fever onset; thereafter, PGE2 was significantly
      reduced by comparison with controls. Indomethacin at 50 mg/kg completely
      abolished both the fever and the increased levels of PGE2 in the POA; the fever
      induced by PGE2 microdialyzed into the POA was not affected by indomethacin
      pretreatment The intracarotid infusion of PGE2 produced T(C) falls and no
      increase in preoptic PGE2 levels. The indomethacin-induced blockade of fever and
      inhibition of the associated increase in preoptic PGE2 levels further
      substantiates the presumptive link between PGE2 in the POA and fever caused by
      LPS. The failure of exogenous PGE2 infusion to induce increases in T(C) and
      preoptic PGE2 levels excludes the possibility that PGE2 formed outside of the
      brain penetrates the POA and induces fever. Thus, in guinea pigs, the PGE2
      associated with LPS-induced fever may be synthesized in the POA.

PMID- 9138751
TI  - National AIDS Malignancy Conference. Bethesda, Maryland, April 28-30, 1997.
      Abstracts.

PMID- 9138750
TI  - Evidence for a dopaminergic involvement in the natriuretic action of centrally
      administered renin.
AB  - Intracerebroventricular (IVT) administration of renin (R) to conscious male
      hydrated rats induces an increase in sodium excretion. The involvement of brain
      dopaminergic neurons in the renal action of IVT-R was investigated. Renin-induced
      natriuretic action was prevented by domperidone and by inhibition of tyrosine
      hydroxylase activity with alpha-methyl-p-tyrosine treatment. In addition, this
      effect was absent following selective central dopaminergic denervation with 6
      hydroxydopamine (IVT) in combination with desmethylimipramine (IP). Our results
      suggest that renin acts centrally, at least in part, via an interaction with
      endogenous dopamine systems.

PMID- 9138752
TI  - [Surgical treatment of radiation-induced lesions of the hip in adults].
AB  - The authors report their experience in the surgical management of lesions of the
      adult hip following radiotherapy. The diagnosis of a hip problem occurring after
      pelvic radiotherapy for malignant tumors is made by clinical and radiological
      examination. The problems include femoral head necrosis, necrosis and/or fracture
      of the acetabulum, or involvement of the entire hip joint (radiation coxopathy).
      Fractures of the femoral neck have been described in the literature, but are now
      very rare following the routine use of external shields as protection during
      irradiation. Post-irradiation lesions are often bilateral 21%. They appear after
      a variable latency period of two to twenty years and they progress remorselessly.
      A diagnosis of simple radio necrosis can only be made after using radio isotope
      bone scanning, MRI or CT to exclude malignant disease as acetabular metastasis,
      and radio-induced sarcomas. Hemiarthroplasty is often followed by collapse of the
      acetabulum and should no longer be used. The treatment generally practised
      nowadays is a Total Hip Replacement (THR). We report a retrospective study of 71
      hips in 56 patients treated, between 1970 and 1982, by the use of conventional
      cemented components. In 49 hips this was followed by a 52% incidence of
      acetabular loosening resulting from the poor quality of the irradiated bone which
      had become necrotic and porotic. Between 1983 and 1990, we modified the technique
      by regularly using reinforcing the acetabulum with a metallic ring fixed by long
      screws, (as used in revision surgery for THR). Bone grafts were also used in 9
      cases. We had a 12% incidence of loosening in 22 hips with a mean follow-up of 40
      months. There were also two post-operative infection which need removal of the
      prostheses. This emphasizes the risk of infection in this type of surgery and is
      probably increased by the associated lesions of the soft tissues (lymphoedema,
      radiodermitis). The authors wish to stress the poor prognosis of radiation
      lesions of the hip which often occur in patients who have otherwise recovered
      from their pelvic tumour. These radiation lesions have to be recognised and
      treated in a specific way. Our experience and the reports in the literature
      suggest that the generally used conventional THR gives uncertain results, and
      therefore we propose a THR employing metallic reinforcement of the acetabulum
      with or without any necessary bone grafts. It is vital to warn the patients that
      the results may not be as excellent as with THR for other types of hip disorders.
      When there is severe destruction of the acetabulum the choice between a THR
      combined with massive bone allograft, and a Girdlestone hip resection must be
      very carefully discussed with the patient. This latter "salvage" procedure may in
      any case become necessary if there are local and otherwise unmanageable problems.

PMID- 9138753
TI  - [Technical advances in the surgical management of thoracoabdominal aortic
      aneurysms].
AB  - Thoracoabdominal aortic aneurysmectomy ranks among the major cardiovascular
      surgical procedures. During the last two decades perioperative results have
      improved to the point that surgery should be discussed in the vast majority of
      patients seen with a thoracoabdominal aortic aneurysm. This progress is largely
      attributable to a variety of technical improvements including: aortic
      reconstruction using the graft inclusion technique, usually with direct
      reattachment of aortic branches to the prosthetic graft; distal aortic perfusion;
      selective use of deep hypothermic circulatory arrest in anatomically complex
      situations; preoperative visualization of arterial blood supply to the spinal
      cord using selective arteriography of intercostal and lumbar arteries. Current
      perioperative mortality is around 10% whereas the spinal cord complication rate
      is between 5% and 20% according to clinical and anatomical conditions. Future
      efforts should concentrate on the prevention of spinal cord complications.

PMID- 9138754
TI  - [Neuronal apoptosis in the course of human immunodeficiency virus infection].
AB  - Apart from the unique changes characteristic of "HIV encephalitis", the
      productive infection of central nervous system by HIV, which involves
      predominantly the white matter and basal ganglia, evidence is accumulating that
      the cerebral cortex may also be affected in AIDS patients. Neuronal loss,
      suspected at microscopical examination, has been demonstrated by a number of
      morphometric studies. However, the cause and mechanism of neuronal damage in HIV
      infection, are still unclear. In an attempt to look for an apoptotic process at
      the origin of neuronal loss in AIDS, we examined samples of frontal cortex,
      temporal cortex and basal ganglia from 12 patients who died from AIDS and 4 HIV
      positive asymptomatic cases using in situ end labelling to demonstrate
      characteristic DNA fragmentation. These were compared with 5 seronegative
      asymptomatic controls, and 2 seronegative patients with Alzheimer's disease. We
      demonstrated neuronal apoptosis in all the AIDS cases and in the Alzheimer's
      cases. Positive in situ end labelling was usually associated with morphological
      changes suggestive of neuronal apoptosis. Semiquantitative appreciation of the
      density of apoptotic neurons showed that neuronal apoptosis was more severe in
      atrophic brains. In contrast, no correlation was found between the density of
      apoptotic neurons and the presence of HIV encephalitis or a history of cognitive
      disorder. Only occasional apoptotic neurons were found in one asymptomatic, HIV
      positive case. Apoptosis was never observed in asymptomatic seronegative cases.
      Experimental studies tend to support our in vivo findings. Infection by HIV of
      primary cultures of human embryonic central nervous system induced frequent
      apoptosis of neurons. No apoptotic cell was identified in non infected control
      cultures.

PMID- 9138756
TI  - [Relationship between world food production and the environment].

PMID- 9138755
TI  - ["De novo" cancer after organ transplantation].
AB  - From March 1972 to 1st of January 1996, 804 kidney, liver and pancreas
      transplants were performed in 690 patients. 39 post transplant cancers occurred
      in 27 patients. 21 skin tumors (15 squamous cell carcinoma, 4 basocellular
      carcinomas, 1 squamous carcinoma, 1 melanoma), 4 squamous cancers (anus,
      esophagus, tongue, and parotid), 4 post-transplant lymphoproliferative disorders,
      1 non-Hodgkin's lymphoma T, 4 gynecological tumors (breast, ovarian peritoneal
      carcinomatosis, 2 uterine cervix cancers), 4 miscellaneous tumors (larynx, right
      colon, brain, prostate, own kidney). 14 patients died (14/27: 52%). Post
      transplant de novo cancers are a major risk in transplant patients These cancers
      are mainly represented by skin tumors and lymphomas. Skin cancers are mainly
      spinocellular and occur in the areas which are exposed to the sun. Post
      transplant lymphoproliferative disorders are very close to Burkitt's lymphoma,
      they produced B lymphocyte proliferation due to the reduction of the control of T
      lymphocytes and induced by Epstein-Barr virus. They can disappear with the
      diminution of immunosuppression.

PMID- 9138757
TI  - [Problems and outlook for plant production].
AB  - Environmental damages due to very intensive cropping systems do exist. A lot of
      people think it is necessary to prohibit the use of chemical fertilizers and
      pesticides, as well as in developed and developing countries. If so, global
      production would dramatically decrease while human population is increasing. The
      objective of feeding population of the world could not be met, particularly in
      Africa. On the other hand, crop modelling shows that theoretical potential plant
      production in the world is sufficient, if environmental damages are avoided.
      Future challenge is double: increasing food production and protecting the
      environment. Different ways to achieve this goal are analyzed. Increasing food
      production only in developed countries is environmentally and economically not
      practicable because of high cost and social damages in developing countries. Each
      country has to increase its own production, particularly in the South. But
      adopting the very intensive cropping systems existing in the North is not
      possible. The challenge is to be able to increase crop production in each place,
      taking into account biophysical, sociological, economical and political
      peculiarities. In some places, existing extensive cropping systems cause damages
      to the environment, because population pressure lead to increase cultivated
      areas, consequently reducing follow and pasture of forest areas: these systems
      are not sustainable if not intensified. In other places, even in the South, water
      pollution results from excessive use of fertilizers and pesticides. A new
      paradigm is proposed to take into account this great diversity of situations: the
      "Doubly Green Revolution" will allow to define adapted and sustainable cropping
      systems. Scientific results obtained along last century and including recent
      results in biotechnology, will be at the basis of these new systems.

PMID- 9138758
TI  - [Problems and outlook for production of land animals].
AB  - Some people look at a decreasing demand for animal products in the near future.
      Today, the diagnosis is that the availability in animal protein are very low in
      many countries. And we must help to improve the efficiency of animal systems in
      different parts of the world for cutting out the disparities and preventing the
      negative effects of the tremendous demographic growth. We worry to observe,
      during the last decades, a higher development of granivorous species (pigs and
      poultry) against herbivorous ones (cattle, horses...). For the future, we can
      take support of the spectacular development in knowledge of all sectors of animal
      production. But we must keep interest for training generalists in the field of
      animal sciences, able to make innovations in animal systems. There is a large
      diversity for conceiving new strategies in animal production. The main limiting
      factor will be the biomass resources as feeds for producing animal foods: oil
      meals and other feeds with high protein content seem to be the more strategies
      because the world production is now 27 kg per capita and the demand in developed
      countries near 100 kg. Animal systems could be aggressive for environment. Some
      examples show a dangerous relationship between a higher density of animals,
      mainly with granivorous fed with imported feedstuffs, and increasing nitrate
      content in the subterranean water. But the risk can and must be controlled.

PMID- 9138759
TI  - [Problems and outlook for animal production in the aquatic environment].
AB  - The major source of aquatic animal production is based on fisheries. Currently, a
      significant portion of the fishery resources is used for non-food purposes. One
      of the first steps towards rational exploitation of the natural fishery resources
      should be to limit such abuse and address the needs of an increasing global
      population. The challenge for the fishery industry is to develop methods for
      early and reliable prediction of stock availability and fluctuations in order to
      maintain a sustainable supply. With the continuing decline in fishery resources,
      aquaculture is slowly becoming an interesting alternative for the supply of
      animal protein of high nutritional value. Aquaculture, like any other human
      activity can have adverse effects on the environment. In this context, the semi
      intensive farming systems prevailing in the tropical areas should be encouraged,
      substantiating them with scientific knowledge on the nutrient flow in such
      confined ecosystems. In some instances of intensive culture systems, progress has
      been made in aquaculture waste management by applying adequate nutritional
      strategies. Such an approach should be extended to other cultured species. Be it
      production for profit or production for food, sustainable aquatic animal
      production is intimately connected with all human activities, in as much as all
      these activities invariably have an effect on water quality. Hence, greater
      consideration is needed towards a general strategy of protecting the aquatic
      ecosystem at all levels.

PMID- 9138760
TI  - [Palliative care--objectives and accomplishments of the Association for the
      Development of Palliative Care].
AB  - Associations involved in Palliative Cares want to develop a better use of
      therapeutic resources and a better support of patients threatened in their Lives.
      They want to help developing of adjusted structures to a better global tacking
      charge of patient and his family in hospital and at home. The Association for
      development of Palliative Cares (ASP) founded 1984 has chosen from the beginning
      the concept of continuous care and has set since 1986 the first coordinated team
      of voluntary "Support", selected and trained, in a curative care unit cancer
      patients with fatal prognostic, after a possible remission. They participated,
      the ASP also, to the architectural conception and the financing of the first unit
      of palliative cares in France. The ASP conceived a help to home support for
      patients in the end of their life, by a team reinforced by a referent nurse, in
      collaboration with a home hospitalisation unit and a pain consulting. The ASP is
      now taking action in Paris and its area, with its 180 volunteers and 12 teams in
      11 Hospitals and one at home.

PMID- 9138761
TI  - [Use of opiates for chronic pain].
AB  - World Health Organization (WHO) has recommended since 1986 simple methods to
      control pain due to cancer. The use of analgesic medications, appropriate to the
      severity of pain reported by the patient, is the key point of WHO guidelines. It
      has been shown that the use of analgesic medication and particularly of morphine
      to control severe pain is insufficient for a majority of patients worldwide. This
      communication presents the main results of French national studies among
      representative samples of cancer patients and physicians (primary care physicians
      and medical oncologists) faced with cancer pain. These studies confirm that
      cancer pain is inadequately treated for 51% of patients and identify among French
      physicians attitudinal barriers to the proper use of morphine. Results are
      discussed with regard to the national policy against pain now in progress in
      France.

PMID- 9138762
TI  - [Eulogy of Paul Groulade (1909-1995)].

PMID- 9138763
TI  - [Time-Temperature indicators (TTI). A means of quality control of produce].
AB  - The author, after having dwelt on the mediatic importance of bacterial food
      poisonings, analyses their reasons, insisting on the importance of the
      temperature as a factor of bacterial growth. Among the cures for the association
      temperature-bacterial growth, the author draws attention to the benefits of the
      use of the time temperature indicators (TTI). He describes the purposes, the
      required qualities, the principles of activity. The "Lifelines TTI" proves to be
      interesting. The author describes the principles of activity, the directions for
      reading the results, the practical application. Finally he describes the remarks
      following on its use in large scale in a group of chain-stores. In the
      conclusion, the author points that these TTI are an attractive technical
      innovation regarding to the fresh foods, for the control of coldness in the human
      nutrition.

PMID- 9138764
TI  - [Sarcoidosis symptomatic cardiomyopathy: report of 10 cases].
AB  - This study illustrated 10 cases of sarcoidosis symptomatic cardiomyopathy. All
      sarcoidosis were confirmed by histology. One was revealed by cardiological signs.
      Extra-cardiologic manifestations were non specific, as well cardiological and
      electrical signs. ECG were abnormal in only 70% of cases. Echocardiography and
      thallium scintigraphy with dipyramidole test were always abnormal. No sudden
      death appeared in our series. As opposed to all cases in literature, all
      patients, but one, responded positively to corticotherapy. These results can be
      explained by high doses of prednisolone associated, when non effective, to
      another immunosuppressive agent.

PMID- 9138765
TI  - National high school survey finds resurgence in marijuana use and increased
      tobacco use.

PMID- 9138766
TI  - Shorter stays, higher per diem charges found in partial hospital, ambulatory
      behavioral programs.

PMID- 9138767
TI  - Earliest phases in the evolution of sickness and healing.
AB  - Sickness and healing constitute the root concepts that center medical
      anthropological inquiry and give the field its identity. Here, they are held to
      manifest a biological adaptation designed by evolution that requires culture for
      its final realization. Sickness and healing thus provide anthropology with a
      biocultural form that has changed in content and expression during cultural
      evolution. The early phases of this evolution, those bearing the most apparent
      influences of the environment of evolutionary adaptedness, are reviewed and
      analyzed in the article. Some of the implications of this for medical
      anthropology are discussed.

PMID- 9138768
TI  - Blood and nerves revisited: menopause and the privatization of the body in a
      Newfoundland postindustrial fishery.
AB  - Ethnographic data from a longitudinal, interpretive study of women's changing
      social and cultural constructions of menopause in a postindustrial, Newfoundland
      fishing village indicate that three major changes have taken place in the way
      women conceptualize female, reproductive life-cycle events and processes. First,
      folk idioms of nerves and blood that once linked soma, psyche, place, and
      tradition are now trivialized and have been superseded by biomedical models of
      menopause. Second, physicians, television, magazines, and school teachers have
      replaced the community's middle-aged women and the mutual communication of shared
      experience as major sources of information and advice on reproduction and aging.
      Third, women's bodies have become privatized, and bodily metaphors that once
      linked women in complex individual and collective assessments of shared, highly
      valued traditions and mutual judgment of moral character have lost their
      dominance in village life.

PMID- 9138769
TI  - Privileged knowledge and mothers' "perceptions": the case of breast-feeding and
      insufficient milk in Bangladesh.
AB  - This article uses the example of breast-feeding and insufficient-milk syndrome in
      Bangladesh to illustrate the privileged status of professional discourse. While
      health professionals' discourse is given the status of scientific knowledge, the
      views and opinions expressed by breast-feeding women are referred to as
      "perceptions" and thus regarded as less objective. We use data gathered in two
      anthropological studies undertaken between 1987 and 1992 to examine some of the
      ambiguous qualities that breast-feeding mothers, their relatives, and health
      practitioners attribute to breast milk in Bangladesh. We discuss how old beliefs
      are incorporated into new systems and how bottles, which are associated with
      allopathy and science, provide a way of circumventing anxieties about female
      physiology and breast milk. Medical, religious, and popular ideas on breast
      feeding and insufficient milk represent different intersecting discourses on the
      same theme-that female physiology and sexuality are problematic.

PMID- 9138770
TI  - Politics, practical logic, and primary health care in rural Haiti.
AB  - During the 1980s, an ambitious project for health development restructured
      medical services throughout rural Haiti. The "Rural Health Delivery System"
      (RHDS) pursued several goals of primary health care, including dispensary-based
      maternal and child health services and the provision of low-cost drugs. Based on
      fieldwork in a single village, this article examines how local residents pushed
      the project in unpredictable and ironic directions. People did not regard
      dispensary services-which were planned and financed by international health
      agencies-as essentially foreign elements in the local health-care system. They
      rather engaged with the dispensary according to long-standing local strategies
      for prestige and economic advance. Despite the dramatically new shape of
      biomedicine introduced by the RHDS, the dispensary remained for most people a
      recognizable arena to gain access to state resources or to contest state control
      over their lives. The "success" of clinic services, and the "failure" of the
      project to distribute essential drugs arose more from people's practical routes
      to symbolic and material power than from the formal plans of health planners or
      state bureaucrats. This practice-based analysis provides another dimension to
      both the liberal and neo-Marxist critiques of international health development.

PMID- 9138771
TI  - Verbal intercourse and sexual communication: impediments to STD prevention.
AB  - This article explores the problems of risky sexual behavior by examining the ways
      people verbally negotiate sexual interaction regarding sexually transmitted
      diseases. Based on in-depth interviews with 124 adults (ages 21-63) who are
      infected with genital herpes, the article shows that knowledge about sexually
      transmitted diseases is not necessarily related to the action needed for their
      prevention. People are more afraid of being rejected by a partner than they are
      of contracting an STD (except, of course, AIDS). By examining difficulties people
      have with sexual health discourse and showing how these difficulties are related
      to both the problem of communicating politeness and the problem of representing
      the self and the sexual other, this article demonstrates that STD prevention
      programs overlook a very important emotional and communicative issue: the lack of
      a culturally sanctioned language with which to discuss sexual health with
      partners.

PMID- 9138772
TI  - DuPont Prize for Receptor Research 1996.

PMID- 9138773
TI  - [Biological activity of tin and immunity].
AB  - Tin generates a wide variety of biological activities deriving from its chemical
      character. In this article, the biological activities of tin compounds are
      reviewed with a focus on the connection with immunity. The table of contents is
      as follows: Introduction, 1. Inorganic Tin and Immunity, 2. Organic Tin and
      Immunity, 2.1. Immunotoxicity, 2.1.1. Immunosuppression, 2.1.2. Thymus atrophy,
      2.1.3. Changes in the membrane surface antigens of T cells, 2.2. Antitumor
      activity, 2.3. Anti-inflammatory action, 2.4. Tolerance manifestation of thymus
      atrophy, 3. Cellular and Biochemical Aspects of the Activity Manifestation, 3.1.
      Intracellular distribution of organotins 3.2. Effects on structure and function
      of Golgi apparatus and endoplasmic reticulum, 3.3. Effects on physical properties
      of phospholipid membrane, 3.4. Suppressive effects on cell proliferation system,
      3.5. Consideration, Conclusion. To sum up this article, tin compounds (especially
      organotin compounds) act mainly on cellular immune systems and the mechanism
      appears to be due to their hydrophobicity-dependent intracellular distribution
      and their action on the phospholipid metabolism including the inhibition of
      intracellular phospholipid transport between organelles through an impairment of
      the structure and functions of the Golgi apparatus and the endoplasmic reticulum
      (ER), and the consequent inhibition of the membrane-mediated signal transduction
      system leading to DNA synthesis via phospholipid turnover and Ca2+ mobilization.

PMID- 9138774
TI  - [Effect of worksite dental health program on periodontal status--evaluation by
      CPITN and bleeding on probing at each tooth].
AB  - A dental health promotion program which aimed to prevent periodontal disease was
      carried out at a shipyard in Nagasaki Prefecture. Repeated tooth cleaning
      instruction and prophylaxis were conducted in order to adopt proper oral hygiene
      habits. The first 3 months of this program included 'Initial instruction,' and
      'Regular instruction' were given every 6 months in following 2 years. The oral
      examination was carried out before and after Initial instruction, and at each
      Regular instruction. The effect of this program was evaluated by 2 measures:
      CPITN and Bleeding on probing. After this program, the rate of teeth with pockets
      4 -5 mm deep or deeper (CPITN 3, 4) was decreased. In contrast, the rate of teeth
      with no sign of periodontal disease (CPITN 0) was increased remarkably: the
      percentage increased from 8% preinitial instruction to 40% with regular
      instruction. Both the rate and grade of teeth with bleeding on probing were
      decreased. These results indicated that this program was helpful in improving the
      periodontal status. CPITN and Bleeding on probing at each tooth as an evaluation
      measure made our analysis more detailed.

PMID- 9138775
TI  - [Reconsideration of evaluation criteria for physical fitness tests of a working
      population--comparing conventional and new evaluation criteria].
AB  - We set up new evaluation criteria values for grip strength, sit ups, trunk
      flexion, standing on one leg with eyes closed, whole body reaction and maximum
      oxygen uptake by age and by sex, by analysing data for about 50,000 people
      collected by the Japan Industrial Safety & Health Association. We thought that
      the conventional evaluation criteria values used in the physical fitness tests
      for a working population did not appropriately reflect the present conditions,
      and so we compared the new evaluation criteria values with the conventional
      evaluation criteria values. As a result, a very significant difference was noted
      in each test item. Then, by examining the quality of the data, change of the
      times, number of persons tested, and characteristics of the groups studied, all
      of which could have caused such differences, it was concluded that the proposed
      new criteria values would be appropriate for evaluation of the physical fitness
      of the current working population.

PMID- 9138776
TI  - [A study of waste anesthetic gases monitoring and working environmental controls
      in hospital operating rooms].
AB  - There are hazardous factors threatening health care workers, and many hazardous
      chemical substances have been reported in operating rooms, central supply
      facilities, laboratories and so on. In Japan, little attention has been paid to
      exposure to these chemicals and to working environmental controls. Waste
      anesthetic gases are chemicals concerned, and we conducted environmental
      monitoring continuously and measured exposure to nitrous oxide, isoflurane and
      sevoflurane in operating rooms, and examined working environmental controls. The
      average environmental concentrations of nitrous oxide were about 400 ppm in
      anesthetists' working areas, and about 180 ppm in surgeons' and instrument
      nurses' working areas under unscavenged conditions. Under scavenged conditions,
      environmental concentrations were 70-190 ppm in anesthetists' zones, and 70-90
      ppm in surgeons' and instrument nurses' zones. Even under scavenged conditions,
      operating room personnel are presumed to be exposed to high concentrations of
      nitrous oxide above ACGIH's TLV and NIOSH's REL. The level of exposure of
      isoflurane and sevoflurane was 2-4 ppm. Managing general ventilation system and
      airflow direction, working area under scavenged system, environmental
      concentration levels of nitrous oxide could be reduced to 20-30 ppm. In order to
      control occupational exposure to anesthetic gases, it is not sufficient to merely
      adapt scavenging systems in operating rooms. Working environmental control and
      occupational hygiene management should be required.

PMID- 9138777
TI  - [A case of autonomic nervous dysfunction caused by technostress who was
      effectively treated with psychosomatic therapy and long rest from work].

PMID- 9138778
TI  - [Current problems in the laboratory control of louse-borne typhus infection in
      Ukraine].
AB  - Surveys designed to study spread of typhus infection (persistent form and Brill's
      disease), and state of laboratory diagnosis in Ukraine showed an important role
      the laboratory diagnosis plays in the system of epidemiological surveillance
      aimed at preventing epidemic typhus. Main trends of activities on perfection of
      the system of laboratory control of the infection under present-day conditions
      are outlined.

PMID- 9138779
TI  - [The effect of carbacholine and noradrenaline on intertissue connections during
      the reparative process].
AB  - Effects of carbacholine and noradrenaline on intertissue relations were studied
      in the experiment on rats experiencing healing of their wounds of the skin.
      Choline- and adrenergic stimulations were shown to both quantitatively and
      qualitatively change the course of posttraumatic regeneration of the skin, which
      developments are accompanied by change of intertissue interrelationships between
      the epidermis and connective tissue.

PMID- 9138780
TI  - [The possible carcinogenic action of a protein concentrate from Saccharomyces
      yeasts grown on molasses].
AB  - A testing was done in a chronic experiment on 300 rats and 360 mice of both sexes
      for carcinogenic potential of a new protein product from Saccharomyces yeast
      grown in melasse. The production procedures and techniques of the above product
      have been worked out at the Ukrainian Research Institute of Spirits and
      Biotechnology of Food Stuffs of Gospishcheprom (State Food Industry) of Ukraine.
      The studies made showed the new protein product has no carcinogenic effect.

PMID- 9138781
TI  - [The diagnosis of micro- and macroangiopathies of the lesser circulation in
      diabetic patients].
AB  - Patients with diabetes mellitus aged under 40 in the state of compensation
      demonstrate significant drop of pressure in the pulmonary artery system as
      compared to the corresponding parameter in those patients with diabetes mellitus
      beyond 40, which fact suggests presence of microangiopathies in the system of the
      pulmonary artery in the absence of concurrent pulmonary diseases and with similar
      duration of the illness.

PMID- 9138782
TI  - [The role of metabolic correction in the combined therapy of middle-aged and
      elderly patients with ischemic heart disease].

PMID- 9138783
TI  - [The rate of healing of an ulcerous defect in the duodenal bulb in relation to
      the site (based on video endoscopic data)].

PMID- 9138784
TI  - [The combined treatment of peptic ulcer with the differentiated use of
      nontraditional physiotherapeutic methods].
AB  - Efficiency was studied of multimodality treatment of 586 patients with ulcer
      disease. Of these, 110 had gastric ulcer, 460 patients had duodenal ulcer,
      sixteen were suffering from both gastric and duodenal ulcer. 275 patients (46.8%)
      had various concurrent chronic disorders involving cardiovascular system and
      alimentary canal. Three groups of patients were identified: those receiving
      magnetoresonance therapy apart from conventional antiulcer therapy (n = 89),
      those undergoing laser therapy (n = 170), those exposed to hyperbaric oxygenation
      (HBO), variable magnetic field (VMF) and acupuncture (AP) according to generally
      accepted techniques. In the control group, drug therapy promoted ulcer healing in
      73.3% of patients, whereas multimodality treatment involving MRT induced healing
      in 80.6% that of incorporating computer-aided laser therapy led to healing in
      85.7 to 89.4%. HBO, VMF and AP group demonstrated healing in 92.4 to 93.7%.

PMID- 9138785
TI  - [Treatment methods for the dumping syndrome].
AB  - An incidence was determined of dumping syndrome after various operations while
      studying results of surgical treatment of gastric and duodenal ulcer in 135
      patients. In dumping syndrome, two variants of association of motility of the
      stomach stump and efferent intestinal loop were identified. Modes of conservative
      treatment are proposed, such as transcutaneous electrostimulation of the
      ileocecal portion of the intestine and prescription of Zbruchansk (naftusia-type)
      mineral water.

PMID- 9138786
TI  - [Principles of the differentiated use of the natural and preformed therapeutic
      factors of a health resort in patients with chronic pancreatitis].
AB  - With the purpose of enhancing efficacy of health-resort treatment of chronic
      pancreatitis, patients with relevant clinical form and stage of the disease
      course, early revealed distinguishing features of disturbances in the exocrine
      function of pancrease should be referred to those health resorts having adequate
      mineral waters. 75 patients with chronic pancreatitis presenting with various
      type pancreatic secretion derived benefit from differentiated use of mineral
      water and physiotherapeutic procedures.

PMID- 9138787
TI  - [Manual therapy of the abdomen and its effect on the homeostatic system of the
      human body].

PMID- 9138788
TI  - [The interrelationship of changes in the vascular bed of the testes to the status
      of the spermogram in the pathogenesis of infertility].
AB  - Infertile marriage is a burning medical and social problem. In spite of this the
      pathogenesis of infertility in men is not at present fully understood. The
      present investigation was designed to study general regularities of interrelation
      between changes in vascular bed of the testis and state of spermogramme in the
      pathogenesis of infertility. As many as 156 infertile patients were enrolled into
      the study, 420 rats Wistar used. Infertility resulted from varicocele,
      cryptorchism, epididymitis, prostatitis, obstruction of the deferent duct as well
      as from effects of electromagnetic field. It has been ascertained that
      progression of structural disorders of the intraorganic and haemomicrocirculatory
      bed of the testis is directly related to worsening of spermogramme indicators.

PMID- 9138789
TI  - [Neurosis-like states in persons who have had a stroke and their correction].
AB  - 198 patients with prior insult were studied. The peculiarities of their neurosis
      like states were described. It was shown that there is the dependence of these
      peculiarities on the localization of the pathological process, etiology of insult
      and personal?

PMID- 9138790
TI  - [The immunological and morphological aspects of hemoperfusion with pig donor
      spleen in treating psoriasis patients].
AB  - The present paper focuses on the immunological and morphological aspects of
      extracorporal joining up of donor porcine spleen in the treatment of psoriasis.
      It has been ascertained that extracorporal joining up of donor porcine in the
      treatment of psoriasis makes for normalization of bodily immunologic reactivity
      leading to regression of psoriatic eruptions.

PMID- 9138792
TI  - [An analysis of syphilis morbidity depending on the time of the incubation period
      and the negative serological reaction].
AB  - The article analyses findings from cases syphilis treated at the clinic of the
      chair of dermatovenereology of the Ukrainian State Medical University in Kiev. It
      is shown that lengths of negativation of seroreaction during the course of
      treatment as well as in the course of negativation of seroreaction while treating
      syphilis patients depend on duration of the incubation period.

PMID- 9138791
TI  - [The current methods in the nontraditional therapy of peptic ulcer (a review of
      the literature and the authors' own data)].

PMID- 9138793
TI  - [The microhemodynamics and immune status of patients with chronic viral lesions
      of the liver and their correction].
AB  - Immunity status was studied together with the condition of microhemodynamics in
      113 patients with chronic persistent hepatitis (ChPH) and 46 patients with
      chronic active hepatitis (ChAH) of viral genesis (HBsAg+). In the period of
      exacerbation of hepatitis, immunity and microcirculation disorders were detected,
      more pronounced in ChAH. Incorporation of antral and parmidine into a combined
      therapy of ChPH patients makes for dispelling of the above disorders in a shorter
      time, promoting earlier convalescence and lengthening of remission.

PMID- 9138794
TI  - [Experience with the elimination of a cholera focus in a psychiatric clinic and
      the measures for its prevention].
AB  - The epidemic process of cholera in a mental-hospital setting is to a great extent
      influenced by specific factors. In view of a danger of cholera being brought into
      a mental in-patient facility the authors insist, based on their own experience,
      that in summer and autumn seasons in South regions and urban settlements with
      unstable, in respect of cholera, epidemic situation, not only patients with
      intestinal disfunction be examined for cholera but all those individuals to be
      managed at above facility. It is all-important for a mental hospital to have a
      plan at their disposal of primary antiepidemic measures to be instituted in case
      dangerous infections will pose too difficult a problem to deal with, with
      pharmacy being envisaged, provided with all the stores required.

PMID- 9138795
TI  - [The individual selection of immunomodulating and vitamin preparations for miners
      who are frequently ill with ARVI].
AB  - Proper selection of immunomodulating and vitamin preparations in those miners
      often ill with ARVI promotes to a great extent both dispelling immunologic
      disbalance in the cellular link of immunity and normalization of the functional
      state. But this action is less effective in respect of specific and unspecific
      humoral factors of the immune system. Individual assessment of effectiveness of
      immunomodulating and vitamin preparations in vitro tests is regarded as a
      justified and promising tool enabling a relevant preparation endowed with
      stimulating effect to be selected and prescription of those substances
      sensibilizing the organism of the always ailing miners to be excluded, thus
      ensuring maximum immunomodulating effect.

PMID- 9138796
TI  - [Means for improving the results of the surgical treatment of patients with
      organic hyperinsulinism].
AB  - Based on the analysis of the medical records of patients studied in a large
      clinical trial, possible ways for improving results of surgical treatment of
      patients with organic hyperinsulinism were outlined. Use of ultrasonic aspirator
      permitted the damage to the main pancreatic duct and great vessels to be avoided
      during surgery. A technique is suggested enabling one to detect a damage to the
      main pancreatic duct during surgery doing away with it in a timely fashion; a
      positive effect has been ascertained of sandostatine in the prophylaxis of
      postoperative complications.

PMID- 9138797
TI  - [The medical effect of magnetic-laser therapy in patients with diabetic
      angiopathies of the lower extremities].
AB  - Conventional antidiabetic therapy with insulin and sugar-lowering agents helps in
      achieving compensation of diabetes mellitus but fails to exert high effect on
      subjective and objective manifestations of diabetic microangiopathies of the
      lower extremities. A course of magnetic-laser therapy results in significant
      reduction of concentration of the lipid oxidation products as one of the
      pathogenetic mechanisms of diabetic microangiopathies, normalization of
      immunologic reactivity as well as attenuation of clinical manifestations of
      hemocirculatory disorders in the lower extremities and improvement of parameters
      of thermo- and rheovasography.

PMID- 9138798
TI  - [A case of chronic active viral hepatitis B combined with HIV carriage, malaria
      and syphilis].

PMID- 9138799
TI  - [A case of toxocariasis].

PMID- 9138800
TI  - [Mortality from malignant neoplasms in Ukraine: an analysis of selected dynamic
      curves].

PMID- 9138801
TI  - [The prevalence, structure and clinical problems of multiple sclerosis in the
      Transcarpathian area based on epidemiological study data].
AB  - As many as 230 patients with disseminated sclerosis were examined in the
      Transcarpathian region. Sick male- and female populations were found out to be
      almost similar. There were more sick persons in the medium-range areas of the
      Carpathian Mountains, with a mean age being 35 +/- 5 years. It has been
      established that intake of spirulina makes for lengthening of remission in those
      patients with disseminated sclerosis.

PMID- 9138802
TI  - [Deontological problems in the psychiatric diagnosis and expertise of
      servicemen].

PMID- 9138803
TI  - [The organization of medical support for women service personnel in wartime].

PMID- 9138804
TI  - [Outstanding Ukrainian scientist and public figure (on the 140th anniversary of
      the birth of Academician Ivan Horbachevs'kyi)].

PMID- 9138805
TI  - [The Kiev Surgical Society].

PMID- 9138806
TI  - [Current treatment methods in myelodysplastic syndromes].
AB  - Modern literary data about the treatment of myelodysplastic syndromes are
      reviewed. There have been analysed traditional methods and recent scientific
      achievements, such as using of the colony-stimulating growth factors and bone
      marrow transplantation.

PMID- 9138807
TI  - [The status of the problem of specific prophylaxis and treatment in diphtheria].

PMID- 9138808
TI  - [The hypothalamic pubertal syndrome].

PMID- 9138809
TI  - [The role of Pseudomonas aeruginosa and Proteus in the etiology of suppurative
      surgical infection].

PMID- 9138810
TI  - [The differentiated treatment of non-insulin-dependent diabetes mellitus (a
      review of the literature and the author's own data)].

PMID- 9138811
TI  - [The treatment of refractory ovarian cancer].

PMID- 9138812
TI  - [The results of the medical examination of forestry industry workers in an area
      under intensified radioecological control].
AB  - Overall ninety five workers engaged in forestry of Ukraine living in the
      controlled territories of this country were examined. Some patients had augmented
      bodily content of cesium-137, the cause of this thought to be related to their
      being resident in the localities with its high concentrations in the soil (above
      15 Ki in sq. km.), failure to observe sanitary and hygienic measures, violation
      of a great many of matters related to everyday life and social conditions. No
      association was found between bodily levels of cesium-137 and pathology. I to II
      degree hyperplasia of the thyroid gland ran its course with no impairement of its
      functions. The most prevalent nosological form among diseases of the respiratory
      system in the examined contingent appeared to be chronic bronchitis. Quantitative
      and qualitative parameters of hemopoesis do not exceed the bounds of the
      populational ones and are consistent with change patterns in chronic disorders of
      the gastrointestinal tract and bronchopulmonary system under ecologic health
      hazard conditions.

PMID- 9138813
TI  - [A comprehensive hygienic assessment of the prevalence of cerebrovascular
      diseases among the population of Kiev Province before and after the accident at
      the Chernobyl Atomic Electric Power Station].
AB  - The population of Kiev Province show higher level of primary morbidity of
      cerebrovascular disorders (CVD) and rate of its increment than on the average in
      Ukraine, as per medicostatistical analysis in space and time of CVD prevalence in
      the studied territories. Among regions in the highest ranks in respect of levels
      and rates of increase in morbidity over five post-Chernobyl years are Ivankov and
      Polesye regions which residents had become victims to ChNPP breakdown. It should
      be noted that in previous years the above regions were rated as being in the
      ranks below the average in the area.

PMID- 9138814
TI  - [The problem of the mental health reserve in selecting applicants for the post of
      operators in atomic electric power stations].

PMID- 9138815
TI  - [Anthropogenic factors of the environment and "Chernivtsy chemical disease"].

PMID- 9138816
TI  - [Aluminum: its current toxicological and hygienic aspects (a review of the
      literature)].

PMID- 9138817
TI  - [The use of nonionogenic surface-active substances in petroleum production and
      the institution of measures to protect the environment].

PMID- 9138818
TI  - [Circadian rhythms and the risk of the development of a myocardial infarct].
AB  - As many as 70 patients were examined under conditions of a cardio resuscitation
      unit to gain insight into relatedness of time of development of acute of
      myocardial infarction (AMI) to its forms and particular clinical picture. The
      highest risk of AMI development was recordable within the time interval of 6-12
      hours with the existing dependence for morning probability of microfocal AMI,
      daytime probability of microfocal and transmural AMI, with significant reduction
      thereof within the interval of 18-24 hours. Lesser probability of AMI development
      within 18-24 hours was closely related to reduction of levels of aspartate
      aminotransferases, lactatdegidrogenases, and creatinphosphokinases in AMI
      patients within this time interval.

PMID- 9138819
TI  - [A comparative study of the membrane-protector efficacy of anaprilin and korinfar
      in hypertension patients].
AB  - Beta-blocker anapriline and calcium antagonist corinfar are highly effective
      hypotensive agents. Drop in diastolic arterial pressure with anapriline therapy
      amounted to 15.9 and 15.6%, with corinfar therapy-to 15.0 and 15.6% in
      hypertensive disease stage I and II respectively. Hypotensive action of corinfar
      might result from correction of impaired cation-transport function of cellular
      membranes, electrolyte homeostasis of cells, phospholipid composition of
      membranes. No dynamics has been revealed of the membrane tests under study during
      administration of anapriline therapy treatments.

PMID- 9138821
TI  - [Basic plans for the combined orthopedic treatment of patients with rheumatoid
      arthritis and involvement of the joints of the lower extremities].
AB  - The paper focuses on the main principles of multi-modality orthopedic treatment
      of patients with rheumatoid arthritis (RA) presenting with the lower limbs
      affection, depending upon stage, activity, as well as particular features of
      disease course, functional incompetence of the joints and the limb as a whole,
      with due regard to the patient's volition and psychological status. It is
      necessary that opportunities for the RA patient's orthopedic rehabilitation be
      found before declaring him to be an invalid.

PMID- 9138820
TI  - [Blood plasma luminescence in ischemic heart disease].
AB  - Low-temperature spectra were measured of blood plasma fluorescence and
      phosphorescence in patients with ischemic heart disease. It has been shown that
      structure of radiation spectra depends upon severity of illness and use of ultra
      violet radiation of blood as a therapeutic procedure. It is suggested that
      radiational processes in blood plasma might be caused by luminescence of
      proteins, lipoproteins and radicals of blood plasma. A conclusion is reached to
      the effect that measurement of spectra of luminescence, phosphorescence under low
      temperatures of blood plasma is of great importance for understanding mechanisms
      of pathological processes and efficiency of the treatment options employed.

PMID- 9138822
TI  - [The use of cryopreserved hemopoietic cells of the human embryonic liver in
      stable depressions of hematopoiesis in cancer patients].
AB  - As many as 29 oncological patients with severe depression of hemopoiesis
      secondary to cytostatic therapy underwent transfusion of fetal liver cells (FLC)
      from human embryos in the 8-12 weeks stage of their development cryopreserved in
      5% DMCO at -196 degrees C as to the method elaborated at the Institute of
      Problems in Cryobiology and Cryomedicine. A strong correlation was found between
      infusion of a certain FLC dose and rise in leucocyte counts, which rise occurred
      by day 13-16 (r = +0.846). A minimum FLC dose for the expected leucocyte count
      rise to be of the magnitude of 3.32.10(9)/1 appeared to be 10(9) cells.
      Transplantation had a beneficial effect on the immune status of the patients.
      There was not a single case of graft-versus-host reaction. The above method has
      been recommended for use in clinical settings.

PMID- 9138823
TI  - [The level of gastrin, insulin and glucagon in the blood and the morphometric
      characteristics of the gastric mucosa in peptic ulcer patients of different
      ages].
AB  - Blood content was studied of gastrin, insulin, glucagon by radioimmunoassay as
      were patterns of histomorphometric picture of gastric mucosa in 120 patients with
      duodenal ulcer before and after treatment. Important age-associated changes were
      found to occur in ulcer disease in the time course of treatment, in blood
      concentration of the above hormones as well as quantitative alterations of cells
      of the gastric mucosa fundal glands.

PMID- 9138824
TI  - [The clinico-morphofunctional status of the esophagogastroduodenal system in
      patients with acne rosacea: the etiological, pathogenetic and treatment aspects].

PMID- 9138825
TI  - [The clinico-immunological characteristics of the treatment of patients with a
      severe course of bronchial asthma using the method of the extracorporeal
      incorporation of pig donor spleen].
AB  - A comprehensive clinical-and-immunological evaluation was done of efficiency of
      treatment of patients with severe forms of bronchial asthma (BA) by hemosorption
      through donor porcine spleen, xenosorption (XS), in 63 patients. XS was found out
      to have a marked positive clinical effect manifested by a considerable decrease
      of frequency of asphyxiation bouts and amounts of inhalation broncholytics being
      taken within the first 24 hours after the procedure. By day 14 from the start of
      XS we succeeded in lowering the systemic corticosteroids maintenance dose on the
      average 2.5 times as little. Positive clinical dynamics correlated with positive
      immunologic changes which revealed themselves in normalization of numbers as well
      as functional activity of T-cells, rise in T-helpers, normalization of content of
      serum immunoglobulins A, M and G, with the parameters characterizing the system
      of phagocytosis approaching the norm, the processes of autoimmunization getting
      more attenuated.

PMID- 9138826
TI  - [The pathogenesis of venous thromboses].

PMID- 9138827
TI  - [The diagnosis of chronic dust-induced bronchitis].
AB  - In dust-induced bronchitis, alterations in the pulmonary parenchyma present
      themselves in the main cellular indices for bronchioalveolar lavage (BAL),
      thought to be of much importance to its diagnosis. A total of 53 patients with
      initial and manifest forms of dust bronchitis underwent BAL. There has been found
      the following: a decrease in the mononuclear phagocyte system cells (MPhS)
      reflecting the state of local cellular immunity; rise in the amounts of
      coniophages, suggesting phagocytic activity of alveolar macrophages (AM) and dust
      blockade of MPhS cells; emergence and augmentation of counts of gigantic Pirogov
      Langhans' cells characteristic of tuberculous granulomas, and also decrease in
      the counts of lymphocytes. There is a striking decrement in the vitality of AM,
      with polycytosis being commonly seen. Detection of granular forms of
      Mycobacterium tuberculosis in BAL and Pirogov-Langhans' cells enables a major
      proportion of "dust-induced bronchitis" to be considered as belonging to the
      silicotuberculous process.

PMID- 9138829
TI  - [The physiological diagnosis of neurocirculatory dystonia].
AB  - The authors of the present article were the first to work out theoretical
      foundations and methods of physiological diagnosis of neurocirculatory dystonia.
      Criteria of tension of myocardial functional structures and central regulatory
      mechanisms have been identified both in healthy subjects and cardiological
      patients. It has been ascertained that degree and systematic character of tension
      cause the physiological risk factors for cardio-pathology to develop, 6 types
      were identified of loading adaptation of the heart caused by extent of its
      tension, in individuals with neurocirculatory dystonia. Each of the types
      disclosed is characterized by a dynamics of the functional volumes proportions as
      well as by peculiarities of the adaptation mechanisms. Physiological diagnosis of
      functioning of the heart is one of major methods of the primary prophylaxis of
      neurocirculatory dystonias as well as prevention of aggravation of their course.

PMID- 9138828
TI  - [The validation of empirical emergency antibacterial therapy in acute
      pyelonephritis].
AB  - As many as 254 patients with acute pyelonephritis were evaluated for the whole
      range of possible inflammatory process pathogens with the aid of automatic
      microbiological system [symbol: see text]. Urine from the urinary bladder, renal
      pelves (as directed) was studied as was biopsy specimen of the kidney. Analysis
      of species range of the identified organisms showed Escherichia coli, Proteus,
      and mycoplasma, enterobacter, coccal flora and pseudomonads to be in 27.9%,
      15.9%, 14.9%, 8.6%, and 5.5% respectively. Analysis of sensitivity of the
      discovered bacteria toward a wide range of antibacterial preparations permitted
      recommending for an urgent antiinflammatory therapy thienam, ophloxacin,
      cyprophloxacin, pephloxacin, norphloxacin, cephoxitin, and cephtriaxone. The form
      of the preparation (parenteral or peroral) will be prescribed depending upon the
      gravity of the course of acute pyelonephritis.

PMID- 9138830
TI  - Children's TeleHealth Network links 3 provinces.

PMID- 9138831
TI  - Know your residency applicants well.

PMID- 9138832
TI  - Osler was good, but...

PMID- 9138833
TI  - Nuclear cardiology in the literature.

PMID- 9138834
TI  - Residual area at risk after anterior myocardial infarction: are ST segment
      changes during coronary angioplasty a reliable indicator? A comparison with
      technetium 99m-labeled sestamibi single-photon emission computed tomography.
AB  - BACKGROUND: The aim of this study was to assess whether, after anterior
      myocardial infarction, ST segment changes during percutaneous transluminal
      coronary angioplasty (PTCA) of the left anterior descending coronary artery
      correlated with the amount of ischemic myocardium in the area at risk, measured
      with 99mTc-labeled sestamibi single-photon emission computed tomography (SPECT)
      during balloon inflation. METHODS AND RESULTS: Quantitative continuous monitoring
      of the ST segment was performed during PTCA of the left anterior descending
      coronary artery in 11 patients, and corresponding SPECT imaging was compared with
      a rest acquisition performed before PTCA. SPECT was quantified by a bull's-eye
      analysis according to main criteria: (1) the planimetered defect size during PTCA
      as an indicator of the size of the area at risk, (2) the change in the
      pathologic/normal area count ratio in the area at risk as an index of the
      severity of ischemia, and (3) the difference between the size of the defect
      during PTCA and at baseline. ST segment changes were correlated to the variation
      in pathologic/normal area count ratio (19% +/- 14%; r = 0.61; p < 0.05) but not
      to the sizes of the scintigraphic defects. CONCLUSION: ST segment changes induced
      by occlusion of the infarct-related coronary artery during PTCA are related
      mostly to the severity of ischemia rather than to the size of the area at risk.

PMID- 9138835
TI  - Diagnostic accuracy of dipyridamole technetium 99m-labeled sestamibi myocardial
      tomography for detection of coronary artery disease.
AB  - BACKGROUND: The diagnostic accuracy of exercise 99mTc-labeled sestamibi and
      intravenous dipyridamole 201Tl-labeled myocardial tomography is established. The
      accuracy of dipyridamole stress 99mTc-labeled sestamibi myocardial tomography for
      the detection of coronary artery disease has not been reported. METHODS AND
      RESULTS: Our purpose was to determine the diagnostic accuracy of same-day, rest
      dipyridamole stress 99mTc-labeled sestamibi myocardial single-photon emission
      computed tomography (SPECT) compared with coronary angiography. Two hundred forty
      four patients who were unable to exercise adequately underwent both dipyridamole
      99mTc-labeled sestamibi SPECT and coronary angiography within 6 months.
      Dipyridamole was administered intravenously in a standard dose of 0.56 mg/kg for
      4 minutes. Cardiac and noncardiac side effects were recorded. The presence of
      coronary stenoses of 50% or greater diameter reduction in each of the major
      coronary arteries was compared with imaging data in corresponding myocardial
      perfusion beds. The patient population was predominately (98.8%) male with a mean
      age of 63 +/- 9 years (range 33 to 83 years). The majority of patients had stable
      angina (88%). Eighty-four patients (35%) gave a prior history of myocardial
      infarction; 44 patients (18%) had a history of congestire heart failure. The
      principal limitation to exercise stress was peripheral vascular disease in 62
      patients (26%). No serious side effects occurred during dipyridamole stress; 14%
      of patients had chest pain and 8% of patients had 1 mm or greater ST segment
      depression. Of the 204 patients with documented coronary stenoses, 43 (21%) had
      single-vessel disease and 161 (79%) had multivessel disease. The sensitivity was
      93% (40/43 in patients with single-vessel disease) and 91% (146/161 in patients
      with multivessel disease). Overall sensitivity was 91%. The specificity was 28%
      (11/40) in this population with a high prestest probability of coronary artery
      disease and posttest referral for cardiac catheterization. CONCLUSION: 99mTc
      labeled sestamibi myocardial tomography in conjunction with intravenous
      dipyridamole stress is a safe and sensitive method for the detection of coronary
      artery disease. The diagnostic accuracy of dipyridamole stress 99mTc-labeled
      sestamibi SPECT for the detection of coronary artery disease is similar to that
      reported for exercise stress 99mTc-labeled sestamibi tomography, making this a
      suitable alternative for the evaluation of patients who are unable to exercise
      adequately.

PMID- 9138836
TI  - Antimyosin antibody imaging in experimental aortic regurgitation.
AB  - BACKGROUND: Fiber dropout and myocyte necrosis precede heart failure in
      experimental aortic regurgitation (AR). The current study aimed to determine
      whether this process can be detected by noninvasive scintigraphic imaging.
      METHODS AND RESULTS: 111In-labeled antimyosin antibody Fab fragment (1 to 1.5
      mCi) (Myoscint) was administered to each of 34 New Zealand White rabbits: 11
      early (3 to 5 weeks) after surgical AR induction; 9 late (98 to 128 weeks) after
      AR induction; 5 normal and 3 sham-operated age-matched with early AR; and 3
      normal and 3 sham-operated age-matched with late AR. Echocardiographic fractional
      shortening was indistinguishable among control, early AR, and late AR groups. In
      vivo gamma camera imaging 24 and 48 hours after isotope administration, post
      mortem heart activity determination (percentage injected dose per gram), and
      autoradiography were performed. At 24 and 48 hours, heart-to-lung counts-per
      pixel ratios from in vivo images were greater (p < 0.05) in the late AR rabbits
      than in each of the three other groups. No significant differences were found
      when early AR and older or younger control rabbits were compared. Heart activity
      (percentage injected dose per gram) in late AR rabbits trended toward higher
      values than in age-matched control rabbits (p = 0.057), but in early AR it was
      indistinguishable from that in the corresponding control (p = 0.413, difference
      not significant). The autoradiographic endocardial/epicardial activity ratio in
      late AR rabbits was greater than in control and early AR rabbits (1.27 +/- 0.13
      vs 1.06 +/- 0.09 and vs 1.13 +/- 0.10, respectively, p < 0.02). CONCLUSIONS:
      Whereas isotope uptake in late AR rabbits differed from that in control and early
      AR rabbits, systolic function was indistinguishable. Thus 111In-labeled
      antimyosin antibody imaging may permit noninvasive detection of AR-induced
      myocardial damage before functional deterioration.

PMID- 9138837
TI  - Combined analysis of resting regional wall thickening and stress perfusion with
      electrocardiographic-gated technetium 99m-labeled sestamibi single-photon
      emission computed tomography: prediction of stress defect reversibility.
AB  - BACKGROUND: The high photon flux and stable distribution of the myocardial
      perfusion agent 99mTc-labeled sestamibi allow the perfusion data to be acquired
      in an electrocardiographic (ECG)-gated mode, such that information on resting
      regional wall thickening may be obtained simultaneously with stress perfusion
      data. The objective of this study was to assess whether visual analysis of
      resting regional wall thickening provided by ECG-gated acquisition of 99mTc
      labeled sestamibi stress perfusion images correlates with and predicts the
      reversibility of stress-induced perfusion defects, potentially obviating the need
      for rest imaging. METHODS AND RESULTS: Fifty-nine patients referred for
      myocardial perfusion imaging were studied with rest and stress single-photon
      emission computed tomographic (SPECT) sestamibi imaging, and the stress perfusion
      data were acquired in an ECG-gated mode. Visual analysis of the presence and
      reversibility of stress perfusion defects on standard imaging was correlated with
      the wall thickening data from the poststress gated SPECT images. Quantitative
      circumferential profile analysis of the short-axis images was performed to assess
      the influence of relative stress perfusion defect severity on the correlation
      between wall thickening and defect reversibility. Among the 72 segments with
      stress-induced perfusion defects and visually apparent wall thickening on ECG
      gated SPECT images, 69 were reversible on rest imaging (positive predictive value
      of 96% for wall thickening to predict stress defect reversibility). Of the 35
      segments with stress-induced defects and no apparent wall thickening on ECG-gated
      SPECT images, however, 14 (40%) demonstrated significant stress defect
      reversibility on rest imaging. This result represents a negative predictive value
      of only 60% for the lack of apparent wall thickening to predict correctly an
      irreversible stress defect. Among the segments with reversible stress perfusion
      defects and visually apparent wall thickening, relative stress sestamibi activity
      was higher (51% +/- 10% [percentage of peak]) than in segments with reversible
      stress defects and no visually apparent wall thickening (39% +/- 4% of peak
      activity [p < 0.0001]). CONCLUSIONS: Visual evidence of wall thickening by
      poststress ECG-gated SPECT sestamibi imaging in the territory of a stress-induced
      perfusion defect correlates highly with stress defect reversibility on rest
      imaging and may obviate the need to perform rest imaging, thereby potentially
      reducing the time and cost involved in myocardial perfusion imaging. The absence
      of visually apparent wall thickening, however, underestimates the prevalence of
      stress defect reversibility on rest imaging; in such instances, rest imaging must
      be performed to differentiate ischemia from infarction in the territory of a
      stress perfusion defect.

PMID- 9138838
TI  - Cardiac sympathetic nerve function assessed by [131I]metaiodobenzylguanidine
      after ischemia and reperfusion in anesthetized dogs.
AB  - BACKGROUND: Accumulation of 131I-labeled metaiodobenzylguanidine ([131I]MIBG), a
      radiolabeled norepinephrine analog, is reduced in infarcted myocardium,
      suggesting loss of cardiac sympathetic nerve viability. Histopathologic studies,
      however, indicate that the nerve endings ae morphologically intact. Experiments
      were therefore designed to determine the mechanism of reduced MIBG accumulation.
      METHODS AND RESULTS: Desipramine, a specific blocker or neuronal norepinephrine
      reuptake, was used to separate the portions of total myocardial [131I]MIBG
      accumulation attributable to neuronal and nonneuronal uptake mechanisms. Sixteen
      dogs underwent circumflex coronary artery occlusion for 60 minutes followed by a
      5-hour reperfusion. [131I]MIBG was injected intravenously 1 hour after
      reperfusion. The left ventricle was removed and incubated in triphenyltetrazolium
      chloride to identify infarcted and viable myocardium within the zone at risk.
      Preliminary studies in sham-operated dogs showed that pretreatment with
      desipramine (5 mg/kg) reduced [131I]MIBG accumulation 4 hours after injection to
      38.9% of untreated controls. Chemical sympathectomy by topical phenol resulted in
      a similar decrease in [131I]MIBG accumulation (to 45.7% of normal), and
      desipramine did not produce further inhibition of [131I]MIBG accumulation over
      that produced by phenol alone, indicating that the inhibitory effect of
      desipramine on neuronal accumulation of [131I]MIBG was essentially complete. In
      dogs undergoing ischemia-reperfusion, myocardial samples from infarcted and
      viable postischemic areas showed 64.5% +/- 11.85 and 84.7% +/- 9.1% of normal
      [131I]MIBG activity, respectively (both, p < 0.01 vs normal area, n = 9). With
      desipramine pretreatment (n = 7), accumulation of [131I]MIBG decreased in all
      areas. Neuronal accumulation was reduced uniformly in infarcted, viable
      postischemic, and normal areas by 30% to 35% compared with sham-operated
      controls. In contrast, nonneuronal accumulation was only 39.3% in infarcted areas
      and 84.6% in viable postischemic areas compared with normal areas, and these
      decreases accounted entirely for the reduced total [131I]MIBG accumulation.
      CONCLUSIONS: Reduced [131I]MIBG accumulation in infarcted myocardium after 60
      minutes of ischemia and 5 hours of reperfusion is attributable to a deficit in
      nonneuronal accumulation and not to decreased accumulation by sympathetic nerves.

PMID- 9138839
TI  - Estimation of attenuation maps from scatter and photopeak window single photon
      emission computed tomographic images of technetium 99m-labeled sestamibi.
AB  - BACKGROUND: In single photon-emission computed tomographic imaging of the chest,
      nonuniform attenuation correction requires use of a patient-specific attenuation
      map. The aim of this study was to determine whether an estimate of the regions of
      the lungs and nonpulmonary tissues of the chest could be obtained by segmenting
      the photopeak and Compton scatter window images in a phantom and in patients to
      estimate patient-specific attenuation maps. METHODS AND RESULTS: The photopeak
      and scatter window slices from 16 consecutive 99mTc-labeled sestamibi perfusion
      studies were segmented interactively. In these studies, visually reasonable
      regions could be obtained by estimating a "cold" lung region from scatter window
      data with additional anatomic information of the myocardium region, the backbone
      and sternum locations, the liver, and the rib cage from the photopeak window
      data. In an anthropomorphic torso phantom study and a patient study, comparison
      was made between the attenuation maps based on segmentation of the emission
      images and transmission imaging with a slant-hole collimator. It was determined
      that good agreement in the estimation of the body regions can be achieved with
      segmentation of the emission images in both the phantom and patient data.
      Attenuation correction using the maximum-likelihood expectation maximization
      method was performed on the phantom and the patient data. In both studies,
      attenuation correction with the segmented attenuation map improved uniformity of
      the inferior wall region in comparison with the other walls. CONCLUSIONS: The
      estimation of patient-specific attenuation maps by segmenting the scatter and
      photopeak window slices of 99mTc-labeled sestamibi studies may be a way of
      reducing the loss of specificity due to attenuation artifacts. The potential
      limitations on the accuracy of correction inherent in the method due to the
      estimation of the regions and assignment of the attenuation coefficients need to
      be determined further, and the method needs to be further automated before it can
      be considered for routine clinical use.

PMID- 9138840
TI  - A primer of biostatistic and economic methods for diagnostic and prognostic
      modeling in nuclear cardiology: Part II.

PMID- 9138842
TI  - Treadmill test scores: attributes and limitations.
AB  - As a general rule, clinicians should attempt to isolate those patient subsets
      whose posttest patient management may be optimally changed by the test referral.
      Use of testing in a heterogeneous population will lead to an increase in the
      false-positive rate with a resultant increase in the rate of normal
      catheterization and higher costs of care. By providing imprecise test results to
      the clinician, a higher rate of cardiac events may be observed as a result of
      lack of care for these patients. In addition, a high rate of normal coronary
      angiograms in patients with positive test results or admissions for subsequent
      myocardial infarctions in patients with normal test results may result in a lack
      of confidence in the imaging results leading to a change in referral to newer,
      untested modalities. Thus to integrate our knowledge of the benefits to exercise
      electrocardiography within the context of clinical decision making and the
      appropriate selection of a noninvasive test, it is clear that physicians may use
      aggregate indexes such as the Duke treadmill score to guide patient care, but
      they should not be relied on to provide definitive evidence. Nor can one make the
      statement that because of the risk stratification ability of the Duke treadmill
      score this modality may be used to supplant stress myocardial perfusion imaging.
      In fact, exercise electrocardiography should be the test of choice for lower risk
      patient populations. However, in more intermediate-risk populations (e.g., known
      coronary disease or abnormal resting electrocardiogram), stress perfusion imaging
      is of established diagnostic and prognostic value. Further, from the exercise
      treadmill test, patients with an intermediate Duke treadmill score would benefit
      from additional noninvasive testing with stress myocardial perfusion imaging.
      This strategy provides substantial prognostic information on which to guide
      subsequent patient care.

PMID- 9138841
TI  - First-pass radionuclide angiocardiography with single-crystal gamma cameras.
AB  - Both multicrystal and single-crystal detectors have been in use for more than 25
      years for measurement of ejection fraction by analysis of images collected during
      the first-pass transit of radionuclides through the heart. Originally,
      multicrystal cameras were preferred, because they provided higher count rates
      than Anger cameras; however, over the years improvements in count rate capability
      and collimator design have enabled Anger cameras to perform equally well. This
      has become an important issue now that readily available 99mTc agents, such as
      sestamibi, enable evaluation of both myocardial function and perfusion from a
      single injection. The technical abilities of a particular camera determine which
      acquisition protocols are most likely to provide clinically useable images for
      the widest spectrum of patients. Electrocardiographic-gated list mode collection
      is highly desirable for first-pass imaging, providing the greatest flexibility of
      data review, rebinning, and analysis. Attention to quality control issues of data
      characterization and processing is important to ensure accuracy and precision of
      all measurements. Accurate determinations of ejection fraction of the left
      ventricle are possible routinely and, under favorable circumstances, of the right
      ventricle as well.

PMID- 9138844
TI  - Proceedings of the 3rd Wintergreen Nuclear Cardiology Invitational Conference.
      July 14-16, 1996.

PMID- 9138843
TI  - Guides to surgical intervention in chronic aortic regurgitation: myocytes file a
      claim.

PMID- 9138845
TI  - Use of gated SPECT imaging in the prediction of myocardial viability.

PMID- 9138846
TI  - [Sleep and heart failure].

PMID- 9138847
TI  - [Echocardiography and nuclear medicine: complementary or alternative methods in
      the study of the ischemic myocardium?].

PMID- 9138848
TI  - [Adaptations of the heart and vessels in arterial hypertension].

PMID- 9138849
TI  - [The pulmonary interstitium in the transition from a physiological state to the
      development of edema].

PMID- 9138850
TI  - [Chronic heart failure and physical activity].

PMID- 9138851
TI  - [Cardiac performance during insulin clamp: its evaluation by bioimpedance
      measurement].
AB  - Ten patients with dilated cardiomyopathy, 7 ischemic heart disease and 3
      idiopathic (7 males and 3 females, mean age 54.8 +/- 11 years), were studied. An
      insulin euglycemic clamp was performed to evaluate the influence of insulin
      infusion on cardiac performance. All the subjects were in NYHA functional class
      II-III and had an ejection fraction < 60% at a previous echocardiographic
      examination. They were submitted to a noninvasive continuous cardiac output
      monitoring by variations of thoracic impedance at three stops: a basal evaluation
      (T0); 1.2 mU/kg/min insulin infusion (T1); 5 mU/kg/min insulin infusion (T2).
      Moreover at the same times Na+, K+, hematocrit (Hct) and catecholamines were
      measured in the plasma. The total time required for the study was about 4 hours.
      Cardiac performance improved as shown by a significant increase in T1 and T2 with
      respect to the basal condition (T0), of ejection fraction: 57.87 +/- 11.3% (T1)
      vs 52.25 +/- 14.1% (T0; p < 0.01); 59.5 +/- 10.7% (T2) vs 52.25 +/- 14.1% (T0; p
      < 0.005); stroke volume: 2.61 +/- 0.5 l/min/m2 (T1) vs 2.01 +/- 0.75 l/min/m2
      (T0; p < 0.001); 3.35 +/- 0.66 l/min/m2 (T2) vs 2.01 +/- 0.75 l/min/m2 (T0; p <
      0.001) and cardiac output: 41.14 +/- 9.1 ml/m2 (T1) vs 38.83 +/- 7.1 ml/m2 (T0; p
      < 0.01); 46.45 +/- 8.56 ml/m2 (T2) vs 38.83 +/- 7.1 ml/m2 (T0; p < 0.001). This
      improvement in cardiac function was not due to an increase in preload because end
      diastolic volume, Hct, Na+ did not differ through the study. Similarly, afterload
      measured as mean blood pressure did not decrease. Cardiac function improvement
      was obtained in the presence of increased catecholamines. In conclusion,
      exogenous insulin infusion was able, in the presence of euglycemic condition, to
      improve cardiac performance. This improvement could be due to a direct inotropic
      effect of insulin perhaps mediated by its metabolic properties on cardiac
      muscular cells and/or by increasing the cellular intake of Ca+2.

PMID- 9138852
TI  - [The psychological evaluation of patients with severe heart failure awaiting a
      heart transplant].
AB  - Because of the limitations resulting from the severity of heart failure, patients
      in the waiting list for cardiac transplantation often show a worsening in their
      social life. They usually present with psychological problems caused by symptoms,
      medical or surgical therapies and consequences on their own work. We have devised
      and utilized an experimental psychodiagnostic protocol to study the psychological
      characteristics of a sample of patients with heart failure (NYHA functional class
      III and IV) candidate to heart transplantation. Our study was particularly aimed
      at investigating the quality of life and the psychological mechanisms of
      adaptation. Findings show a strong attempt of denying the discomfort deriving
      from the disease and the expectation for transplant. Patients seem to have an
      adequate reaction to the illness and, otherwise, they feel anxiety and trouble
      that make very fragile their psychological adaptation. This behaviour is probably
      correlated with symptoms and the clinical history of heart failure, and does not
      match with a visible state of well-being that can be detected with a superficial
      analysis. Nevertheless patients have a good availability in receiving a
      psychological support from the whole medical staff (physicians, nurses): this
      suggests that the benefits deriving from a contemporary medical and psychological
      therapy are able to prevent the appearance of clear psychiatric symptoms.
      Additional studies involving larger samples of selected populations are needed to
      confirm the results of the present investigation.

PMID- 9138854
TI  - [Familial aortic dissection in a young woman. A clinical case and review of the
      literature].
AB  - A case report of aortic dissecting aneurysm in a 29-years-old woman is described.
      The father died of rupture of a dissecting aneurysm with acute hemopericardium at
      the age of 46 years. Histologic examination of the aortic wall revealed a loss of
      mucopolysaccharide-like material in the media and cystic medial changes. This
      dramatic familial cluster of aortic dissecting aneurysm suggests a genetically
      inherited disease although the basic defect remains to be found out.

PMID- 9138853
TI  - [The effects of chronic beta-blocker administration on respiratory sinus
      arrhythmia].
AB  - The results of studies on the effect of beta-adrenergic blockade on respiratory
      sinus arrhythmia (RSA) are discordant. In some studies in which an increased RSA
      was reported, central vagotonic activity has been proposed. The aim of this study
      was to verify whether chronic beta-adrenergic blockade is capable of increasing
      RSA, and therefore vagal outflow, and to analyze whether the mechanism of action
      is central or peripheral. Twenty normal subjects (mean age 28 +/- 2 years) were
      randomized to receive a hydrophilic (nadolol, N), a lipophilic (metoprolol, M)
      beta-blocker and placebo (PL). After 1 week of therapy a spectral analysis was
      made of the variability in heart rate and systolic blood pressure (SBP) while
      they controlled their breathing at 16 breaths/min for a period of 5 min. The high
      frequency component was calculated for the RR interval (HF-RR, RSA measure) and
      SBP (HF-SBP), and the squared coherence (K2) and phase functions (phi HF) were
      assessed between RR and SBP fluctuations in the respiratory band (RR-SBP); a
      negative phi HF means that RR changes follow SBP changes. The alpha HF (an index
      of the baroreflex gain) was also calculated. Both beta-blockers increased the
      mean RR interval (PL 808 +/- 21, N 1054 +/- 30, M 1031 +/- 27 ms; p < 0.0001), HF
      RR (PL 6.3 +/- 0.3, N 7.1 +/- 0.3, M 7.2 +/- 0.3 ln-ms2; p = 0.002) and alpha HF
      (PL 13.6 +/- 1.5, N 21.9 +/- 2.8, M 24.5 +/- 3.6 ms/mmHg; p < 0.002), and both
      modified phi HF (PL -0.23 +/- 0.05, N -0.02 +/- 0.05, M -0.03 +/- 0.04 s; p <
      0.0001). No difference was found between N and M. Chronic beta-adrenergic
      blockade enhanced RSA and baroreflex gain and reduced the phase between the RR
      interval and SBP oscillations. Since no difference was found between the
      hydrophilic and the lipophilic beta-blockers, these changes seem to be due to a
      peripheral effect.

PMID- 9138855
TI  - [Ventilation and heart failure: evaluation parameters].

PMID- 9138856
TI  - 'Til death do us part: a case of failed affection.

PMID- 9138857
TI  - The promiscuous receptor: a case for the guardian enzyme.

PMID- 9138858
TI  - Chaos in the Hall of Mirrors.

PMID- 9138859
TI  - Stretching the evidence in the case of cardiac growth.

PMID- 9138860
TI  - Role of free radicals and substance P in magnesium deficiency.

PMID- 9138861
TI  - Gateways, gangways, getaways and the one-trick dog misjudged.

PMID- 9138862
TI  - Trophic or non-trophic? That is the question.

PMID- 9138863
TI  - A structural diaster: an indermining of underpinnings.

PMID- 9138865
TI  - Gynecologic laparoscopy and hysteroscopy in a day clinic: trends and
      perspectives.
AB  - We have increased the performance of minimally invasive gynecologic surgery from
      about 15% to 20% of operations a year, especially hysteroscopies and
      laparoscopies, many of which are performed in a free-standing ambulatory unit. In
      1992 our team performed 8057 outpatient operations, significantly more than in
      1991. As the techniques are developed, the number of indications for these
      operations expands. By maintaining high standards, even with major endoscopic
      procedures, we have a very low complication rate.

PMID- 9138864
TI  - Tissue factor pathway inhibitor: from unknown coagulation inhibitor to major
      antithrombotic principle.

PMID- 9138866
TI  - Pseudomembranous enterocolitis after gynecologic endoscopy.
AB  - A 21-year-old nulligravida underwent diagnostic hysteroscopy and laparoscopic
      potassium-titanyl-phosphate laser ablation of pelvic peritoneal endometriosis
      (revised American Fertility score of 10) for dysmenorrhea, dyspareunia, and
      dyschezia. Preoperatively the patient had an electrolyte bowel preparation but no
      antibiotic prophylaxis. Six days postoperatively she developed symptoms of
      nausea, vomiting, and diarrhea, which were not affected by diet and over-the
      counter bowel medications. Examination of stool samples for culture, ova,
      parasites, and Clostridium difficile toxin led to the diagnosis of C. difficile
      pseudomembranous enterocolitis. The patient was referred to a gastroenterologist.
      She required 4 months of metronidazole therapy, including two hospitalizations,
      before her symptoms resolved. The stool assay became negative for C. difficile
      toxin 6 months after surgery. Pseudomembranous enterocolitis may occur rarely in
      patients without the usual risk factors of antibiotic therapy. The role of
      electrolyte bowel preparation is uncertain, but it may have permitted overgrowth
      of C. difficile.

PMID- 9138867
TI  - Essential principles of electrosurgery in operative laparoscopy.

PMID- 9138868
TI  - Operative laparoscopy: American Association of Gynecologic Laparoscopists, 1993
      membership survey.
AB  - The American Association of Gynecologic Laparoscopists' 1993 membership survey on
      operative laparoscopy had 1205 respondents reporting 80,031 procedures.
      Diagnostic laparoscopy remains the most common procedure, followed by
      adhesiolysis and laparoscopically assisted vaginal hysterectomy. This survey was
      particularly designed to chronicle the rate of complications as increasingly
      complex laparoscopic procedures are performed.

PMID- 9138869
TI  - Treatment of submucous fibroids, and outcome of assisted conception.
AB  - STUDY OBJECTIVE: To determine the effect of hysteroscopic resection and goserelin
      in the treatment of submucous fibroids, and their significance in assisted
      conception. DESIGN: Patients with history of subfertility and previous failed
      attempts at assisted conception were examined by transvaginal sonography before
      further attempts at assisted conception. Those diagnosed as having submucous
      fibroids were treated with goserelin injections, hysteroscopic resection, or a
      combination of both. Saline sonohysterography was performed whenever the
      submucous nature of the fibroid was unclear. SETTING: The Churchill Clinic
      Fertility and IVF Centre, London, United Kingdom PATIENTS: One hundred women
      being treated for subfertility over a period of 2 years. Twenty-seven had
      submucous fibroids diagnosed by transvaginal sonography, and a comparable group
      of 73 had a normal uterine cavity. INTERVENTIONS: Three doses of goserelin 3.6 mg
      subcutaneously at 4-week intervals were given, followed by hysteroscopic
      resection of the submucous part of fibroids if the fibroids remained submucous.
      Three patients had hysteroscopic resection without goserelin, as the fibroids
      were resectable when they were diagnosed. All patients underwent assisted
      conception within 3 months unless they conceived spontaneously in the interim.
      MEASUREMENTS AND MAIN RESULTS: The pregnancy rate in patients with normal uterine
      cavity was 26%/embryo transfer, and 15.8% of these ended in a miscarriage. The
      pregnancy rate was significantly higher (p >0.02) in the study group after
      treatment of submucous fibroids (48.2%/embryo transfer), and the miscarriage rate
      of 23.1% was not significantly different. CONCLUSIONS: Submucous fibroids are a
      significant cause of subfertility. A combination of goserelin injections and
      hysteroscopic resection significantly improves pregnancy rates without increasing
      the miscarriage rate.

PMID- 9138870
TI  - Biopsy diagnosis and conservative surgical treatment of adenomyosis.
AB  - STUDY OBJECTIVE: To diagnose adenomyosis by vaginal ultrasound and percutaneous
      or transcervical myometrial biopsy, and use the results to choose treatment and
      assess prognosis. DESIGN: Evaluation of 31 consecutive women referred by other
      physicians. SETTING: A private gynecologic practice. PATIENTS: The women had
      menstrual symptoms that had not responded to medical treatment or uterine
      curettage. INTERVENTIONS: Myometrial diagnosis was made by percutaneous
      ultrasound-guided needle biopsy, by transcervical electrosurgical loop biopsy at
      the time of endometrial resection, or by needle biopsy at the time of laparoscopy
      or laparotomy. Endometrial resection was performed in 15 patients, laparoscopic
      myometrial reduction in 7, and excision of adenomyotic myometrium or localized
      adenomyoma in 8. MEASUREMENTS AND MAIN RESULTS: Cure was defined as relief of
      menorrhagia and dysmenorrhea. Endometrial resection cured menorrhagia in 12 of 15
      patients but dysmenorrhea in only 3 of 8; myometrial excision cured 7 of 8, and
      myometrial reduction 4 of 7 women. CONCLUSIONS: Vaginal ultrasound combined with
      transabdominal or transcervical myometrial biopsy established the diagnosis of
      adenomyosis in all patients. Endometrial resection and myometrial reduction or
      excision reduced the need for hysterectomy to 30% in these women.

PMID- 9138871
TI  - Potential limiting factors in resident training for laparoscopic management of
      ectopic pregnancies.
AB  - STUDY OBJECTIVE: To evaluate resident exposure and training in operative
      laparoscopic management of ectopic pregnancy (EP). DESIGN: A review and
      comparison of the profile and management of consecutive series of patients with
      EP in two different clinical settings. SETTING: A university-affiliated
      obstetrics and gynecology residency program caring for indigent women, and a
      private, office-based infertility practice. PATIENTS: Fifty-three consecutive
      patients with EP treated surgically in an infertility practice (group 1) were
      compared with 68 such women managed in a residency program (group 2). RESULTS:
      Evaluation at the time of hospital admission confirmed significantly lower
      systolic and diastolic blood pressures (mean +/- SD 106.2 +/- 12.2 mm Hg vs 114.8
      +/- 9.1 and 61.1 +/- 14.4 mm Hg vs 71.7 +/- 11.8 mm Hg, p <0.05) and hemoglobin
      (10.9 +/- 2.7 g/dl vs 12.2 +/- 2.2 g/dl, p <0.05), and higher pulse rates (96.1
      +/- 12.1 bpm vs 84.0 +/- 7.7 bpm, p <0.01) for groups 2 and 1, respectively. The
      mean gestational age at diagnosis was greater in group 2 (52.1 +/- 14.8 days)
      than in group 1 (46.7 +/- 11.1 days, p <0.05). That the overall clinical picture
      in group 2 was more serious was confirmed by a larger mean gestational mass (4.4
      +/- 3.1 cm vs 2.8 +/- 2.6 cm, p <0.01), more frequent rupture (69% vs 21%, p
      <0.01), and a larger hemoperitoneum (547 +/- 488 ml vs 215 +/- 202 ml, p <0. 05).
      Similarly, 49% of group 2 patients required postoperative or intraoperative blood
      transfusion, compared with 13% of group 1 (p <0. 01). Forty-four of 53 women in
      group 1 were managed laparoscopically (83%), whereas only 16 (24%) in group 2
      were so treated (p <0.05). CONCLUSION: Patients in group 2 were more
      hemodynamically compromised, had more advanced gestations, and had more ruptured
      EPs, leading to decreased opportunities for laparoscopic management. Active
      resident participation in operative management of nonindigent women with EP may
      be necessary to ensure appropriate training.

PMID- 9138872
TI  - Laparoscopic Pomeroy tubal ligation in a residency training program.
AB  - STUDY OBJECTIVE: To evaluate the efficacy of the laparoscopic Pomeroy method of
      tubal ligation as a teaching tool during the initial acquisition of advanced
      laparoscopic skills by 14 residents in a 28-person, 4-year program. DESIGN: A
      prospective, nonrandomized study. SETTING: A metropolitan teaching hospital.
      PATIENTS: Fifty-seven women who desired permanent sterilization, and 56 controls
      who underwent laparoscopic sterilization by standard coagulation. One refused
      entry and had standard sterilization by bipolar coagulation. In two women, both
      with several previous laparotomies, visualization of the pelvic organs was
      incomplete and the procedure was abandoned at the discretion of the surgeon. One
      had a minilaparotomy Pomeroy tubal ligation and the other was sterilized by
      standard two-puncture laparoscopic coagulation. One patient was excluded due to
      an incomplete data profile. INTERVENTIONS: Laparoscopic sterilizations using the
      Pomeroy technique and standard coagulation were performed by gynecology residents
      with an attending physician present. First-year residents performed 36 (68%) of
      the 53 procedures. MEASUREMENTS AND MAIN RESULTS: Operative times to teach this
      technique to house officers rotating on the gynecologic service were recorded by
      postgraduate year and stratified by the number of cases performed by each
      operator. The average operative times for residents in postgraduate years 1
      through 4 were 18.6, 15.4, 21.7, and 14.8 minutes, respectively. These diminished
      with experience. A statistically longer time of 7.1 minutes was required to teach
      residents the Pomeroy technique compared with standard bipolar coagulation
      (p<0.0003). CONCLUSION: Laparoscopic Pomeroy tubal ligation as a method to begin
      educating residents in advanced operative video-laparoscopy appears to have great
      potential.

PMID- 9138873
TI  - Laparoscopic evaluation and treatment of women with chronic pelvic pain.
AB  - STUDY OBJECTIVE: To evaluate the effectiveness of operative laparoscopic
      treatment at the time of diagnostic laparoscopy in patients with chronic pelvic
      pain (CPP). DESIGN: A retrospective study of women with CPP and at least 6 months
      of follow-up after laparoscopic evaluation and treatment. SETTING: A faculty
      practice and community teaching hospital. PATIENTS: A series of 65 consecutive
      women with greater than 1 month of pelvic pain who underwent laparoscopy. Thirty
      two were referred by other physicians for evaluation of CPP. INTERVENTIONS:
      Patients had operative laparoscopic treatment of all abnormal findings at the
      time of diagnostic laparoscopy. Nonspecific treatment such as presacral
      neurectomy or uterine nerve ablation was not performed. MEASUREMENTS AND MAIN
      RESULTS: After laparoscopic evaluation and treatment, 78% of patients had
      decreased pain and 45% were pain free. Prior unsuccessful medical or surgical
      treatment did not affect the response rate. Endometriosis and adhesive disease
      were the most common diagnoses, 38% and 34%, respectively. CONCLUSIONS:
      Laparoscopic surgical treatment of pathology noted at the time of diagnostic
      laparoscopy in women with CPP is appropriate, but less than one-half of patients
      may be expected to have complete pain relief.

PMID- 9138874
TI  - Comparison of minimally invasive surgery and laparotomy in the treatment of
      adnexal masses.
AB  - STUDY OBJECTIVE: To compare the outcome of laparoscopic treatment of adnexal
      masses with treatment by laparotomy. The procedures, their duration, and
      associated complications also were evaluated. DESIGN: Women were randomized to
      undergo either procedure based on the ward to which they were admitted. SETTING:
      A university teaching hospital. PATIENTS: The 192 patients were admitted with a
      preoperative diagnosis of adnexal mass. INTERVENTIONS: Surgical procedures were
      cystectomy, salpingectomy, oophorectomy, and unilateral or bilateral salpingo
      oophorectomy. Organ-preserving techniques were used wherever possible. All tissue
      specimens were examined histologically. MEASUREMENTS AND MAIN RESULTS: The mean
      duration of surgery was statistically not significantly different between the
      groups, 96.8 minutes for minimally invasive surgery, and 116 minutes for
      laparotomy. Organ preservation did reach statistical significance at 65.7% and
      17.2% respectively (p <0.001). Postoperative morbidity was statistically lower in
      patients undergoing minimally invasive procedures. Preoperative tumor marker
      levels did not correlate well with postoperative histology. One woman in the
      laparotomy group had histologically proved ovarian cancer. Minimally invasive
      surgery was converted to laparotomy in three patients in whom malignancy was
      suspected at the start of operation. CONCLUSIONS: Laparoscopic management of
      adnexal masses has definite advantages over laparotomy, for example, lower
      postoperative morbidity. In addition, intraoperative endoscopic diagnosis is
      highly accurate, and the frequency of unnecessary procedures is lower.

PMID- 9138875
TI  - Laparoscopic retropubic cystourethropexy.
AB  - STUDY OBJECTIVE: To evaluate the efficacy of laparoscopic retropubic
      urethrovesical suspension. DESIGN: Retrospective review of charts of 62 women
      over a follow-up period ranging from 8 to 30 months. SETTING: A suburban hospital
      in a major metropolitan area. PATIENTS: Sixty-two women, age 34 to 69 years,
      gravidity 0 to 8, and parity 0 to 7, with gynecologic abnormalities requiring
      surgical intervention and with pure genuine urinary stress incontinence.
      INTERVENTIONS: Each patient underwent a Burch or Marshall-Marchetti-Krantz
      procedure, modified to be performed at laparoscopy. MEASUREMENTS AND MAIN
      RESULTS: Success was measured subjectively and objectively. Subjective success,
      determined by the lack of need to wear pads, was 100%. Objective success was
      assessed using several criteria: comparison of preoperative and postoperative
      symptom diaries; questionnaires; urine characteristics by straight catheter
      (office dipstick for nitrate, leukocyte estrace, bacteria, and white cell blood
      count, if suspicious urine culture and sensitivity); postvoid residual volume
      (<100 ml was considered complete); urethrovesical junction angle as determined by
      catheter or Q-Tip placement (upward, downward, or straight); bladder support; and
      negative standing stress test. All women reported satisfactory relief of
      symptoms, with subjective and objective improvement. None have noted urinary
      leakage during activities similar to those preoperatively associated with this
      condition. CONCLUSION: To date, the outcomes have been acceptable, although the
      limited numbers and relatively short follow-up prohibit any definitive
      conclusions.

PMID- 9138876
TI  - Introduction of laparoscopically assisted vaginal hysterectomy in a private
      teaching community hospital.
AB  - STUDY OBJECTIVE: To compare laparoscopically assisted vaginal hysterectomy (LAVH)
      with traditional total abdominal hysterectomy (TAH) when the laparoscopic
      approach is introduced into a private hospital. DESIGN: During 1 year, 49 LAVHs
      were performed and compared with 51 consecutive TAHs using retrospective chart
      review and statistical analysis. SETTING: A private, university-affiliated,
      teaching hospital. PATIENTS: All patients undergoing LAVH, and the first 51 TAHs
      performed during the study year. MEASUREMENTS AND MAIN RESULTS: No major
      complications occurred in either group. Significant differences were observed in
      uterine weight (161 +/- 92 g vs 331 +/- 354 g), operating time (164 +/- 48 min vs
      108 +/- 28 min), and hospital stay (2.93 +/- 1.21 days vs 4.00 +/- 1.54 days) for
      LAVH and TAH, respectively. Hospital charges for LAVH average $4074 more than for
      TAH, primarily due to the use of disposable laparoscopic equipment. CONCLUSIONS:
      Laparoscopically assisted vaginal hysterectomy may be performed safely in a
      private community hospital with appropriate surgeon credentialing and training.
      Modifying techniques to minimize the use of disposable equipment would make the
      procedure more cost effective.

PMID- 9138878
TI  - An operative technique for laparoscopic hysterectomy using a retroperitoneal
      approach.
AB  - The technique used for abdominal hysterectomy does not lend itself well to a
      laparoscopic approach because vital structures will be difficult to visualize and
      retroperitoneal spaces difficult to open. An entirely different approach is
      required. An operative technique for laparoscopic hysterectomy is based on a
      systematic dissection of the retroperitoneum in a very precise sequence of
      operative steps. It provides complete control of the operative field and allows
      visualization of all important retroperitoneal structures. The technique is
      simple to learn, and requires no special surgical skills beyond what is necessary
      for routine laparoscopic gynecologic procedures.

PMID- 9138877
TI  - Clinical and financial analyses of laparoscopically assisted vaginal hysterectomy
      versus abdominal hysterectomy.
AB  - STUDY OBJECTIVE: To perform clinical and financial analyses of laparoscopically
      assisted vaginal hysterectomy (LAVH) and total abdominal hysterectomy (TAH).
      DESIGN: During the 16 months between August 1991 and December 1992, 34 women who
      underwent LAVH were compared with 60 women having TAH during 1990. Indications,
      surgical outcomes, complications, time to return to work, and hospital charges
      for each group were analyzed. SETTING: A multispecialty group practice. PATIENTS:
      The LAVH group included the first 34 cases by the senior author and were the only
      such procedures at this hospital. The TAH group included all patients having this
      procedure for benign conditions from the same group practice for 1990.
      Interventions. Either LAVH or TAH. MEASUREMENTS AND MAIN RESULTS: The most common
      primary indication in both groups was fibroids. Only one LAVH failed and was
      converted to a TAH. Postoperative complications were significantly greater for
      TAH than for LAVH (45% vs 9%). The length of stay and time to return to work were
      significantly less after LAVH. Total hospital charges increased for LAVH over TAH
      ($7623 vs $4550) despite a significantly shorter length of stay after LAVH.
      CONCLUSIONS: Although LAVH has a significantly lower complication rate than TAH,
      it is more costly to perform. This higher cost, despite a shorter hospital stay,
      is attributed to high operating room charges. Employers and patients benefit from
      early return to work with LAVH.

PMID- 9138879
TI  - Low-cost office laparoscopic sterilization.
AB  - Between September 1986 and February 1992 we performed 210 laparoscopic tubal
      ligations in our office under local anesthesia using the Hulka clip. During the
      last 2 years we used a microchip video camera and endocoagulated the fallopian
      tubes adjacent to the clip in 84 women. The length of time for each procedure
      ranged from 15 to 30 minutes (average 20 min). There were no intraoperative
      complications. Failure to tolerate abdominal lifting (the "belly" test) was the
      only contraindication in this series. Previous abdominal surgery was not a
      contraindication. The three known failures in our first 69 cases were thought to
      be inaccurate clip applications. Subsequently, we added endocoagulation to the
      technique. Our procedure is cost efficient and time saving for both patients and
      physicians.

PMID- 9138880
TI  - Clinical applications of Lin's forceps in flexible hysteroscopy.
AB  - Eighty-one patients underwent directed biopsy with a large Lin's biopsy forceps
      during flexible hysteroscopy performed without cervical dilatation or anesthesia.
      Ninety-seven specimens were obtained, with an average size of 74.5 3(. For
      control study, 18 women underwent directed biopsy with a small conventional
      biopsy forceps. Nineteen specimens were obtained, with average size 3.4 mm3( (p
      <0.05). In eight women, lost intrauterine devices were retrieved with a large
      Lin's grasping forceps, which can easily grasp the device directly and remove it
      during flexible hysteroscopy.

PMID- 9138881
TI  - The relationship of different power settings and fiber geometries to thermal
      tissue damage created by the superpulse Nd:YAG laser.
AB  - We attempted to quantify the amount of thermal damage that was created to
      surrounding tissues when an incision was made with the superpulse
      neodymium:yttrium-aluminum-garnet (Nd:YAG) laser with the optical fiber in
      contact. Light micrographic studies of several incisions, at different laser
      power settings and with different fiber geometries, were made in the anterior
      abdominal wall of 16 Sprague-Dawley rats. The specimens were collected
      immediately postoperatively and at 48 hours postoperatively. Several laser power
      settings (2-50 W) and seven different optical fiber geometries were studied. The
      micrographs showed minimal damage (<0.1 mm) to surrounding tissues at all laser
      power settings in both the immediate and the 48-hour studies. The superpulse
      Nd:YAG laser with optical fiber contact limited laser thermal damage to the
      surrounding tissues to less than 0.1 mm in the range of power settings studied.
      Higher power settings minimally increased the damage. The geometries of the
      optical fiber created no significant alteration in thermal damage. The results
      suggest that the superpulse Nd:YAG laser creates both thermal and photodisruptive
      effects in tissue.

PMID- 9138882
TI  - Nonpenetrating, arcuate-legged clip reconstruction of the rat uterine horn.
AB  - A new method for reconstructing rat uterine horn was developed in which
      nonpenetrating, arcuate-legged clips are applied in interrupted fashion to
      everted seromuscular edges, forming an elastomeric flanged joint. This
      anastomosis has unusual physical and morphologic properties, with improved tissue
      healing and luminal restitution. Clipping is easier than suturing, and resulted
      in equivalent fertility rate (50-60%) and litter size. It also is associated with
      less granuloma formation and hystiocytic infiltration than suture. The new
      technique has the potential of endoscopic translation for human tubal
      reconstruction.

PMID- 9138883
TI  - A new vaginal extractor for laparoscopic surgery.
AB  - We developed a new instrument specifically designed to facilitate the removal of
      large tissue masses through a vaginal incision during laparoscopic surgery
      without any loss of gas. It consists of a cannula fitted with a ball-shaped head
      at one end. After laparoscopic culpotomy, tissue is seized with a grasping
      forceps introduced vaginally through the cannula. To prevent dissemination and to
      facilitate passage through the incision, tissue masses may be placed in a tied
      plastic pouch prior to extraction. The entire procedure is safe because of
      continual endoscopic control. It was performed in 57 women to extract cysts,
      tubal pregnancies, adnexa, myomas, and ovaries. It took an average of 10 minutes,
      and no intraoperative or postoperative complications were observed. Preliminary
      experience suggests that this technique is safe, fast, inexpensive, and easy to
      perform under continuous endoscopic control.

PMID- 9138884
TI  - Laparoscopically assisted hysterectomy for uteri weighing 500 g or more.
AB  - We attempted to determine the feasibility and results of laparoscopically
      assisted vaginal hysterectomy (LAVH) for removing symptomatic fibroid uteri not
      suitable for vaginal hysterectomy. We retrospectively reviewed cases in which the
      uterus weighed 500 g or more and was considered not suitable for traditional
      vaginal hysterectomy after examination under anesthesia. Laparoscopically
      assisted hysterectomy with or without unilateral or bilateral adnexectomy was
      successfully completed in 20 (91%) of 22 cases. Thirteen patients had concurrent
      laparoscopic lysis of adhesions, and one a laparoscopic bladder neck suspension.
      Mean uterine weight was 837 g, mean operating time 167 +/- 42 minutes, mean blood
      loss 390 +/- 107 ml, and mean hospital stay 2.6 days. No febrile morbidity or
      surgical complications occurred among these patients. The only significant
      intraoperative complication was bleeding requiring blood transfusions, which
      occurred in one of the two women who required abdominal hysterectomy. Our results
      suggest that LAVH is a safe and effective alternative to total abdominal
      hysterectomy of the very large fibroid uterus, and that conversion to total
      abdominal hysterectomy could be expected to occur in less than 10% of cases.

PMID- 9138885
TI  - Omental herniation through a 5-mm laparoscopic cannula site.
AB  - Herniation is a rare complication of laparoscopy, and has not previously been
      reported to occur through a 5-mm puncture site. A patient experienced an
      incarcerated omental prolapse through an incision for a 5-mm cannula 4 days after
      undergoing a laparoscopic radical hysterectomy. Based on our experience, we
      recommend fascial closure of all laparoscopic cannula insertion sites if
      possible, and emphasize the need for evaluating omental or enteric protrusions
      through even small fascial defects.

PMID- 9138886
TI  - Incarcerated hernia after laparoscopically assisted vaginal hysterectomy.
AB  - Herniation of small bowel through a fascial defect (Richter hernia) created at
      laparoscopy is a rare complication, but it occurred in a 54-year-old woman after
      a laparoscopically assisted vaginal hysterectomy. One must question whether or
      not increasing cannula sizes are associated with greater numbers of laparoscopic
      complications.

PMID- 9138887
TI  - A multicenter review of 839 laparoscopic-assisted vaginal hysterectomies.
AB  - A multicenter review of 839 cases of laparoscopic-assisted vaginal hysterectomy
      (LAVH) was conducted to contribute to the clinical decision-making process
      regarding the procedure, which has been the subject of much debate in recent
      years. The results suggest that patients undergoing LAVH experience complication
      rates no higher than those having any other type of hysterectomy, and that
      efficacy is identical to that of vaginal hysterectomy. Furthermore, the
      laparoscopic approach affords better visualization of pelvic pathology and better
      adnexal access for the accomplishment of concurrent pelvic procedures. Mean
      hospital stay is 1.7 days and mean recovery time 20 days. The notion of a
      learning curve as described by diminishing procedure time and declining
      complication rates over time is not supported by this data set. Patients who may
      traditionally have faced abdominal hysterectomy due to putative or demonstrated
      pelvic pathology may benefit the most from LAVH.

PMID- 9138888
TI  - Four major areas of intraoperative safety at hysteroscopy.

PMID- 9138889
TI  - Comment on the article by Leuken et al (2(3)269-272, 1995)

PMID- 9138890
TI  - The effect of aggregation state of amphotericin-B on its interactions with
      cholesterol- or ergosterol-containing phosphatidylcholine monolayers.
AB  - Amphotericin B (AmB) is the most effective antibiotic used in the treatment of
      systemic fungal infections. It is generally thought that the activity of this
      drug results from its interaction with ergosterol, the main sterol of fungi
      membranes. However, AmB also interacts with cholesterol, the major sterol of
      mammal membranes, thus limiting the usefulness of this drug due to its relatively
      high toxicity. The aim of the present work is to study the molecular basis of the
      interactions of AmB with these sterols contained in a DOPC film by using the
      monolayer technique. Two different concentrations of the sterols in the film (13
      and 30%) at an initial surface pressure of 30 mN/m were studied, which correspond
      to conditions found in various biological membranes. Four concentrations of AmB
      in the subphase, ranging from a molecularly dispersed to a highly aggregated
      state of the drug were studied. Our results show that the monomeric form of AmB
      interacts with the ergosterol containing film solely. On the other hand, when AmB
      is dispersed as a pre-micellar or as a highly aggregated state in the subphase, a
      very significant selectivity of its interactions between the two sterols is
      observed which is shown in our experimental results by a difference of 8 mN/m in
      the surface pressure when AmB interacts with ergosterol as compared to
      cholesterol. We show that the activity of AmB is most likely related to the
      micellar form of the antibiotic. In addition, we observe that upon increasing the
      amount of ergosterol in the film, the insertion of AmB is largely promoted,
      results that are discussed in terms of the molecular organization of the sterols
      within the monolayer film. We show that these results provide a better
      understanding of the action of AmB (activity/toxicity) at the membrane level.

PMID- 9138892
TI  - Partial liquid ventilation with Perflubron in premature infants with severe
      respiratory distress syndrome.

PMID- 9138891
TI  - Possible involvement of nonbilayer lipids in the stimulation of the activity of
      cytochrome P450SCC (CYP11A1) and its propensity to induce vesicle aggregation.
AB  - Phosphatidylcholines with saturated branched fatty acyl chains substituted in the
      2-positions of the main chains have a significant stimulating effect on both the
      side chain cleavage activity of cytochrome P450SCC and the ability of P450SCC to
      induce a specific vesicle aggregation in lipid-vesicle reconstituted systems.
      Stimulation increases with increasing content of the branched
      phosphatidylcholines and is sensitive to its acyl chain structure and
      composition. Because branched phosphatidylcholines containing 2-alkyl substituted
      fatty acid chains belong to a new class of phosphatidylcholines forming inverted
      nonbilayer phases the results indicate that nonbilayer lipids might play an
      important role in the function of mitochondrial P450SCC.

PMID- 9138893
TI  - Quantification of nucleic acids.
AB  - Quantification of nucleic acids is an area of growing importance in the clinical
      laboratory. In addition to routine measurements of total nucleic acid
      concentrations, quantitative techniques are used to determine the number of
      microorganisms in samples, the level of expression of genes, or the presence of
      alterations in gene dosage. This article provides an overview of current
      methodologies for measurement of total and specific nucleic acid concentrations.

PMID- 9138894
TI  - Use of DNA polymorphisms to monitor engraftment after allogeneic bone marrow
      transplantation.
AB  - Bone marrow transplantation (BMT) has been established as a life-saving procedure
      in hematologic malignancies and bone marrow failure syndromes, and it may be
      valuable in other types of neoplastic disease. DNA polymorphisms are used to
      monitor engraftment after transplantation from a related or unrelated donor. DNA
      polymorphisms are not useful after autologous BMT or if the donor is an identical
      twin. The most valuable polymorphism for this purpose is caused by variation in
      certain repeated sequences that are known as variable number of tandem repeats
      (VNTR). The VNTRs are valuable because they each have several alleles increasing
      the probability of finding one that is useful in a given case. This method can be
      used to sensitively detect small amounts of residual recipient hematopoiesis. To
      accomplish this the laboratory must first find a polymorphic allele that is
      unique in the recipient. Detection of the unique allele in peripheral blood or
      bone marrow after BMT is tantamount to finding recipient hematopoiesis. The
      presence of both donor and recipient hematopoiesis can result in a state of
      stable mixed chimerism and not necessarily presage a relapse after BMT for
      leukemia; however, the presence of residual recipient cells in some cases may
      indicate an increased probability of relapse, particularly in chronic myelogenous
      leukemia.

PMID- 9138895
TI  - Detection of Mycobacterium tuberculosis by molecular methods.
AB  - A review of the current literature regarding performance of the polymerase chain
      reaction and transcription mediated amplification with respect to diagnosis of
      tuberculosis is presented. Additional studies of the usefulness of these methods
      for predicting the efficacy of treatment by amplification of rRNA and DNA are
      also discussed. Application of the methodologies to nonrespiratory specimens for
      diagnosis of tuberculosis are presented.

PMID- 9138896
TI  - Simultaneous multianalyte nucleic acid detection for gastrointestinal bacterial
      pathogens using GeneSTAR technology.
AB  - The use of Gene-based simultaneous target amplification and recognition
      (GeneSTAR) technologies allows for the rapid detection of five different
      bacterial gastrointestinal pathogens from stool sample. The process involves DNA
      isolation, multianalyte polymerase chain reaction (PCR) amplification and single
      base mismatch detection in a microtiter plate format. The analysis is instrument
      compatible and can be completed in less than five hours.

PMID- 9138897
TI  - Cytogenetics. An evolving role in the diagnosis and treatment of cancer.
AB  - Conventional cytogenetics has been used for many years in the diagnosis and
      follow-up of myeloproliferative disorders. Molecular techniques including FISH
      and gene rearrangements are complementary in the evaluation of myeloproliferative
      and myelodysplastic disorders. Lymphomas and lymphocytic leukemias have nonrandom
      cytogenetic patterns that are useful in the clinical diagnosis, prognosis, and
      therapeutic follow-up. Solid tumors have complex karyotypic and genetic
      abnormalities, and clinical utilization of conventional cytogenetics and
      molecular techniques is in the developmental stages of applicability. The
      benefits of karyotype analysis in myeloproliferative and lymphoproliferative
      diseases include guidance for diagnostic and therapeutic approaches as well as
      assessment of minimal residual disease. Conventional cancer cytogenetics and
      commercially available FISH reagents enhance these applications. Molecular
      diagnostic techniques are analytically sensitive and specific. The complexities
      of the function and role of genetic abnormalities in solid tumors present
      challenges in the choice, interpretation, and application of conventional
      cytogenetic and molecular data. These challenges offer exciting potential for
      future advances.

PMID- 9138898
TI  - Clinical and molecular aspects of multiple endocrine neoplasia.
AB  - The discovery that RET proto-oncogene mutations are responsible for MEN2 and FMTC
      was a landmark from the perspective of many, including the geneticist involved in
      basic science, the molecular diagnostician, the clinician, and MEN2/FMTC
      families. The discovery has provided basic information concerning the role of
      proto-oncogenes and proto-oncogene activation. The identification of MEN2/FMTC
      associated mutations has also allowed for the availability of direct mutation
      analysis in the routine clinical laboratory. The discovery has resulted in
      definitive risk assessment for members of FMTC/MEN2 kindreds and improved
      management of RET mutation carriers. The discovery also links two realms of
      genetics that are often separated: cancer genetics and "classic" mendelian
      disorders. Finally, information concerning the molecular basis of Hirschsprung
      disease indicates that our understanding of the phenotypic consequences of RET
      mutations is considerable but not yet complete.

PMID- 9138899
TI  - Molecular diagnostics for cystic fibrosis.
AB  - There have been great advances in the understanding of cystic fibrosis since the
      CF gene has been cloned and sequenced. We can now use DNA diagnostic techniques
      to provide information for the physician and families that help with diagnosis of
      the disease. We can also identify individuals at risk of having a child with CF,
      either in families in which there is a history of the disease or in the general
      population. It is hoped that the future will bring more effective treatment in
      the form of gene therapy or new drugs based on our improved knowledge of the
      molecular pathology caused by the various mutations.

PMID- 9138900
TI  - A molecular view of the neurologic porphyrias.
AB  - At the present time, the use of molecular techniques for diagnosing the
      neurologic porphyrias is limited mainly to those laboratories doing research in
      the area. Because any of four genes may be involved, it is important to confirm
      the diagnosis in the index case before undertaking molecular investigation. With
      advances in methodology, it may eventually become possible to test for the many
      mutations that cause these disorders in a simple, cost-effective manner.

PMID- 9138901
TI  - Sequence-based diagnosis of hemoglobinopathies in the clinical laboratory.
AB  - Electrophoresis at alkaline and acid pH values is the most widely used method for
      screening for hemoglobinopathies in the clinical laboratory. Nevertheless, the
      method does not provide definitive diagnostic information for a number of
      hemoglobins. New automated DNA sequencing techniques make it possible to
      definitively identify mutations which cause hemoglobinopathies. Moreover these
      techniques take about the same time as it takes to perform hemoglobin
      electrophoresis and globin chain electrophoresis. Although the reagent cost is
      somewhat higher, the results are definitive.

PMID- 9138902
TI  - Alpha thalassemia and its impact on other clinical conditions.
AB  - Mild alpha thalassemia is the most prevalent genetic trait worldwide. We have
      recently developed a multiplex polymerase chain reaction method to screen for the
      most common deletions which give rise to alpha thalassemia. The authors have used
      this method to investigate a potential association of alpha thalassemia with
      hypertension. Our results show that the prevalence of hypertension in
      hospitalized blacks who have the -alpha 3.7 deletion is 71 percent higher than
      the prevalence in hospitalized blacks who do not have the deletion. The authors
      present a potential mechanism to explain this association.

PMID- 9138903
TI  - The health of prisoners. Proceedings of a symposium. 3 March 1993.

PMID- 9138904
TI  - MAP kinases in mitogenesis and development.

PMID- 9138905
TI  - Sperm competition: evolution and mechanisms.

PMID- 9138906
TI  - The cellular basis of sea urchin gastrulation.

PMID- 9138907
TI  - Embryonic stem cells and in vitro muscle development.

PMID- 9138908
TI  - The neuronal centrosome as a generator of microtubules for the axon.

PMID- 9138909
TI  - The role of the epididymis in the protection of spermatozoa.

PMID- 9138910
TI  - [beta-Receptor blockers: a new principle in the therapy of heart failure?].

PMID- 9138911
TI  - [Endoscopic study of the small intestine with push enteroscopy. A prospective
      study].
AB  - OBJECTIVE: To evaluate whether push enteroscopy of the small bowel (PES),
      undertaken after extensive previous investigations in suspected intestinal
      bleeding from an uncertain site, chronic diarrhoea or lymphoma of the small
      intestine, contributes to the diagnosis, and to ascertain the results of PES and
      its clinical significance. PATIENTS AND METHODS: 56 consecutive patients (29 men,
      27 women; mean age 63 years) were investigated prospectively. The main
      indications for PES were the search for the source of intestinal bleeding in 79%
      of patients (group A), chronic diarrhoea or tropical sprue in 16% (group B) and
      search for tumour of lymphoma in 5% (group C). PES was always performed in
      fasting patients under sedation/analgesia using a video PES, which contrary to
      catheter enteroscopy provides a channel for intervention. RESULTS: In group A 27%
      of patients were found to have lesions, in particular angiodysplasias, or (in
      once case) leiomyoma. Half of these patients were successfully treated
      endoscopically without later surgical intervention being required (mean follow-up
      of six months). In the other half operation became necessary, either because the
      disease itself indicated it or the bleeding persisted, the source being in the
      more distant small intestine and thus not accessible to endoscopic intervention:
      only 50% of the length of the small intestine proved to be within reach of the
      instrument. No abnormalities were discovered in patients of groups B and C.
      CONCLUSION: In cases of gastrointestinal bleeding from an uncertain source PES
      should be performed first, because in many cases it may obviate surgical
      intervention. But PES seems to contribute little of diagnostic value in other
      indications.

PMID- 9138912
TI  - [Thoracic radiography as routine within cardiological diagnosis?].
AB  - OBJECTIVE: As chest radiography is still frequently used routinely in patients
      suspected of heart disease, the study was undertaken prospectively to assess its
      value in view of the potentials of modern noninvasive methods. PATIENTS AND
      METHODS: History, physical examination, electrocardiography, ergometry,
      echocardiography and colour Doppler echocardiography as well as chest radiography
      were undertaken in 201 consecutive patients (113 men, 88 women, age 60 [3-88]
      years) with known or suspected cardiac valvular defects or heart failure.
      Subsequently invasive investigations were performed in 92 of these patients.
      RESULTS: The value of chest radiography depended on the nature and severity of
      the particular cardiac disease. The diagnosis was established without chest
      radiography in all defects (40 patients) of grade III or IV (New York Heart
      Association) or NYHA class III or IV heart failure (30 patients). Chest
      radiography provided no additional prognostic or therapeutic information.
      CONCLUSION: These data indicate that routine chest radiography is of no value as
      a screening method in patients with chronic heart failure or cardiac defects,
      except in a few clearly defined specific circumstances.

PMID- 9138914
TI  - [Stress-echocardiography. The indications, methods, relevance].

PMID- 9138913
TI  - [Myocardial infarct and rhabdomyolysis after a high-voltage accident with
      successful resuscitation].
AB  - HISTORY AND CLINICAL FINDINGS: A 25-year-old man working as varnisher near a
      power transmission line sustained a 110,000 V shock. Immediately cardiopulmonary
      resuscitation (CPR) of the pulseless and unconscious man by lay personnel was
      continued after 5 minutes by an emergency physician. Normal cardiac rhythm was
      established after 25 electrical defibrillating shocks and 25 minutes of CPR. He
      was then taken to hospital by helicopter. On admission the intubated and
      ventilated patient was precariously stable on high doses of catecholamines. His
      blood pressure was 100/60 mm Hg, the heart rate 110/min. There were current marks
      on both hands and the left foot; part of the right pectoral muscle was contracted
      bulge-like. Creatine kinase activity in serum was raised to 2070 U/l (MB fraction
      174 U/l). The ECG showed significant ST-elevations in V2-V4. TREATMENT AND
      COURSE: At first most attention was paid to stabilising cardiac function. The
      activity of serum creatine kinase rose to a maximum of 13,881 U/l during the
      first 6 hours. To prevent renal failure caused by the marked rhabdomyolysis large
      fluid volumes were administered while intracardiac pressures were monitored via a
      right-heart catheter and urinary alkalization obtained. The precordial leads of
      the ECG showed an evolution of changes as in an anteroseptal infarction, the
      latter confirmed echocardiographically by hypo- and akinesia of the anterior
      wall. The patient was successfully extubated after 32 hours and was symptom-free
      without cerebral impairment after 13 days. As subsequent coronary angiography was
      normal the previous signs of myocardial infarction were most likely caused by
      current-induced vasospasms. CONCLUSIONS: Immediate resuscitation measures after
      high-voltage shock can prevent physical and mental damage. The rare diagnosis of
      acute myocardial infarction requires careful consideration because the usual
      diagnostic criteria of enzyme abnormalities and symptoms cannot be used.

PMID- 9138915
TI  - [Angiostatin. A biological inhibitor of tumor angiogenesis].

PMID- 9138916
TI  - [Late reperfusion in acute myocardial infarct. The importance of the open infarct
      vessel].

PMID- 9138917
TI  - [The vaccination responsibility for the employees of general medical practices].

PMID- 9138918
TI  - [The mercury burden in a family due to a beauty care ointment].

PMID- 9138919
TI  - [Is an endoscopic-bioptic monitoring program for Barrett esophagus sensible?].

PMID- 9138920
TI  - [The status of diagnosis of Barrett esophagus. An analysis of 1000 histologically
      diagnosed cases].
AB  - OBJECTIVE: To evaluate the quality of diagnosis in cases of Barrett's oesophagus
      (BOe). It was examined whether: (1) there had been regular pre-treatment
      investigations;(2) characteristic mucosal changes had been recognized by
      endoscopy; (3) a diagnosis of intraepithelial neoplasia had been made more often
      than of advanced Barrett carcinoma. PATIENTS AND METHODS: Endoscopic and
      associated bioptic reports on 1000 consecutive patients with histologically
      confirmed BOe, seen between 1990 and 1995, were analysed. (Average age was 63 +/-
      14.3 years; male to female ratio: 2.2:1). RESULTS: In 85.1% of patients the
      histological diagnosis was BOe without dysplasia. The neoplasias consisted of
      carcinoma in 8.8%, suspected carcinoma in 0.5%, actual or suspected low-grade
      dysplasia in 4.6%, actual or high-grade dysplasia in 1.0%. Endoscopic diagnosis
      in cases without neoplasia was in 60.8% correct for actual BOe or suspected BOe.
      At endoscopy dysplasia was suspected in 5.4%. The diagnosis or suspected
      diagnosis of Barrett's carcinoma was correct in 69%. Repeat endoscopy a year
      after the initial diagnosis was performed in 9.4% with BOe and no neoplasia.
      Repeat endoscopy was performed in 37.5% of patients with an initial diagnosis of
      suspected low-grade dysplasia, in 43.3% with low-grade dysplasia, in 42.9% of
      suspected high-grade and in 100% of actual high-grade dysplasia. CONCLUSION:
      Neoplasia in Barrett's oesophagus is found too late. Only half of the
      histologically confirmed cases are found by endoscopy and follow-up is not
      sufficient.

PMID- 9138921
TI  - [Argon plasma coagulation through a flexible endoscope. Evaluation of a new
      therapeutic method after 1606 uses].
AB  - BACKGROUND AND OBJECTIVE: Argon plasma coagulation (APC) through a flexible
      endoscope provides a new technique for thermal devitalization or blood
      coagulation which is gaining wider attention. This study was undertaken to test
      clinically the efficacy, safety and ergonomics of the method. PATIENTS AND
      METHODS: 697 consecutive patients (386 men, 311 women; mean age 67 years [3
      months--97 years]) had undergone the procedure in 1606 sitting since 1991.
      Applications included various forms and causes of bleeding in the upper or lower
      gastrointestinal tract or bronchial system, malignant and benign tumours,
      ingrowth of tissues and over-growth in stents, fistulas and, since 1993,
      angiodysplasias and other dysplasias. RESULTS: The precisely defined therapeutic
      aim was achieved in nearly all cases during an average of 2.3 sittings per
      patient, while it failed in 1.5%. Perforations occurred in 5 (0.31%), ending
      fatally in one. Intestinal wall emphysema was diagnosed in 8 cases (0.5%), all
      remaining symptom-free. During a mean follow-up period of 23 (1-72) months there
      were no other serious immediate or late complications or side effects ascribable
      to the procedure. CONCLUSION: APC is a new efficacious, repeatable, safe and
      easily learned method for devitalization of tissues and for achieving
      haemostasis, especially for bleeding from surfaces. Similar applications are
      being developed in other specialties.

PMID- 9138922
TI  - [Leiomyosarcoma of the inferior vena cava].
AB  - HISTORY AND CLINICAL FINDINGS: In a 34-year-old woman who underwent ultrasound
      investigation because of recurrent pyelonephritis a space-occupying lesion in the
      liver was an incidental finding. Computed tomography (CT) and magnetic resonance
      imaging (MRI) confirmed a tumour in segment I of the liver. The patient had been
      on contraceptives for 12 years. She had no symptoms. INVESTIGATIONS: Laboratory
      tests, including tumour markers, were unremarkable. Diagnostic tests to exclude
      malignant tumour with metastases were negative (thyroid scintigraphy,
      mammography, coloscopy and gastroscopy). Further tests (ultrasound, coeliaco
      mesentericography, hydro-CT and spiral CT, MRI) revealed a tumour, 5 x 4 x 4 cm,
      in segment I of the liver, most likely an adenoma. Surgical intervention was
      indicated by the size and questionable malignancy of the tumor. TREATMENT AND
      COURSE: At operation a tumour was found which originated from the inferior vena
      cava (IVC) and displaced segment I of the liver. The tumour was resected and the
      venous wall reconstructed with a Goretex patch. Histological examination
      indicated a poorly differentiated leiomyosarcoma of the IVC. Adjuvant
      radiotherapy was undertaken postoperatively. There has been no evidence of
      recurrence after 10 months. CONCLUSIONS: Leiomyosarcoma of the IVC can be
      mistaken, both by ultrasound and tomographic diagnostic procedures, for a tumour
      in segment I of the liver, especially an adenoma. A leiomyosarcoma of the IVC
      should be included in the differential diagnosis of an hepatic tumour that lies
      close to segment I of the liver.

PMID- 9138923
TI  - [Spiroergometry. Indications, methods, relevance].

PMID- 9138924
TI  - ["Saint Anthony's fire:" ergotamine-induced vascular spasms as the cause of acute
      ischemic syndrome].

PMID- 9138925
TI  - [Arterial hypertension and obstructive sleep apnea].

PMID- 9138926
TI  - [Cystitis treatment with immunoactive Escherichia coli fractions].

PMID- 9138927
TI  - [Functional dyspepsia: approved equal to approved therapy?].

PMID- 9138928
TI  - [Can Suicide be Prevented? Symposium proceedings. Bordeaux, France, June 25,
      1995].

PMID- 9138929
TI  - [Psychobiology of suicide].

PMID- 9138930
TI  - [Epidemiology of suicide].
AB  - Epidemiology for suicide cannot give precise numbers: between 440,000 (WHO) and
      818,000 persons in the world commit suicide each year. For Europe, suicides
      increased regularly to a maximum in 1982-84 (median = 17/100,000). Suicide
      victims tend to be younger. The author doubts that psychiatric causes can explain
      suicide and be the only factor of importance for prevention. Suicide of
      adolescents is only the visible tip of a general behavior learned since
      childhood. The suicidal "solution" (ideas, parasuicides, attempted suicides, and
      suicides) is probably a social phenomenon. Efficacious prevention requires a
      global societal approach. Programs of research and prevention in the Netherlands
      are presented.

PMID- 9138931
TI  - [Epidemiologic and molecular genetic of suicidal behavior].
AB  - The current understanding of suicidal behaviors is that such behaviors are
      multidetermined and mental state and trait related. Genetic factors appear to be
      of great importance, as suggested by the findings of family, twin, and adoption
      studies. Whether these genetic factors are similar to those involved in the
      susceptibility to psychiatric disorders closely related to suicidal behavior (eg,
      manic depressive illness, schizophrenia or substance use disorders) is yet
      unknown. However, a genetic factor of susceptibility to suicide, independent or
      additive to the genetic transmission of the psychiatric disorders that are
      related to suicidal behavior, is strongly suggested by the data of the Copenhagen
      adoption study and a study of Amish families. Recently, new approaches have been
      proposed to identify the genetic component of such complex traits. Association
      studies between genetic markers and a disease phenotype has been successfully
      applied to several complex disease such as essential hypertension. One candidate
      gene for suicidal behaviors is the tryptophane hydroxylase (TPH) gene which is
      the first and possibly rate-limiting enzyme of the metabolic pathway for
      serotonin. Indeed, altered serotoninergic function in both completed suicide and
      suicide attempt has been one of the most replicated findings in modern biological
      psychiatry. In our knowledge, only two studies have tested the association
      between suicide attempt and the TPH gene and their authors found negative
      results. Despite these negative results, association studies that use candidate
      gene remain one of the methods of choice for studying the genetic component of
      suicidal behaviors.

PMID- 9138932
TI  - [The Hungarian suicide enigma].
AB  - Hungary has had a traditionally high suicide rate in the last century. With a
      twofold increase between 1960 and 1985, this country had the highest recorded
      suicide rate in the world. This dramatic increase was due to an extreme high
      suicide mortality in elderly people. A very strong age effect, especially in
      women, is a unique phenomenon. Further demographic, epidemiological, psychosocial
      and biological investigations were carried out in the recent years, and
      overviewed here briefly. Post-mortem psychiatric assessment of suicide victims,
      biological research and epidemiological data suggest that undiagnosed and
      untreated depression is a significant factor in the high suicide mortality.

PMID- 9138933
TI  - [Suicide in Portugal].
AB  - Firstly suicide and parasuicide are defined and their respective characteristics
      are described. Some classifications of suicide and suicidal behaviors are
      analysed, mainly those which emphasize the clinical aspects. Certain models which
      undertake to explain the suicide are briefly reviewed, namely those which see the
      suicide as a deviant behaviour as well as those which see the suicide as a
      disease. Some epidemiologic features of suicide and parasuicide in Europe are
      reported, with special emphasis on Portugal. Suicidal risk factors, namely
      biomedical, psychological, social, cultural, environmental and symptomatic are
      analysed. The predictive evaluation of suicide is pointed out and some suicide
      prevention strategies are discussed. Finally the dependence of suicide on
      individual life cycles, on psychological, social and cultural conditions and on
      cultures and societies cycles is considered.

PMID- 9138934
TI  - [Suicide in adolescence].
AB  - With 1500 death each year, suicide does represent the second cause of death in
      young people (between 15 and 25 years). There is a clear increase of suicide rate
      during adolescence, with an higher rate of suicide attempts in females, but an
      higher mortality in boys. Suicidal behaviors in adolescents are clinically
      characterized by impulsivity, rhythmicity (during schooling) and seasonality.
      Risks factors are numerous. However, psychiatric disorders represent the main
      one, especially depressive states, conduct disorders and their association. In
      adolescents familial and environment events may have an important role in
      suicidal behaviors, especially the role of imitation behavior. These different
      factors interact and constitute dynamic models. The role of each factor can be
      involved differently considering the sex. Dangerosity of suicide in adolescents
      should not be under-estimated, as it has been the case in the past. It is
      particularly true if we consider the high rate of recidive (approximatively 50%)
      in this population. These data emphasized the importance of a careful evaluation
      of all suicidal adolescents more precisely of depressive symptoms and aggressive
      and/or delinquent behavior and of prevention.

PMID- 9138935
TI  - [A strategic theory of suicide].
AB  - A strategic theory of suicide assures that any suicide or attempted suicide is a
      solution to a problem affronted by a person. The basic question is: "who seeks
      what solution to what problem by killing oneself or by attempting to do it?" This
      position allows to distinguish between a dozen different meanings of suicidal
      conducts. By an escape, somebody tries to get out of an unbearable position;
      depending on the circumstances, the situation is more or less realistic, so that
      it becomes feasible to question the state of the mind of the subject. Instead, in
      an appeal, a subject tries to ring a bell, expressing a need to be helped to
      live. Other meanings are grief, revenge, blackmail, sacrifice, ordeal... The
      question "who?" can be answered depending on the meanings and the circumstances.
      One can show the impact of the status of the mind, of age, gender, status, of a
      series of indicators pertaining to suicide and attempted suicide. Some
      statistical observations can be explained in this way. In a third point, it is
      argued that this theory is able to explain how some factors have a bearing on
      suicide, be it war, the economic cycle, or some more profound cultural patterns,
      such as nervous breakdown as an ethnic illness or the modern process of
      individualization. In a final section, a point is made about the possibility of
      deducing from the theory some kinds of therapy, one bearing on the connections
      linking the family, the other building on sessions of "problems solving". On the
      contrary, one has to keep sceptical about preventing suicides.

PMID- 9138936
TI  - [Suicide and psychotropic drugs].
AB  - Suicide provocates 0.5 to 1% of the deaths in France. Suicide appears to be
      closely related to psychiatric morbidity. History of depression is associated
      with a 30-fold increase in suicide risk. Globally, the annual incidence of
      suicide among depressives is 1% and 15% of the depressives die by suicide. When
      depressive symptoms are retrospectively assessed, it appears that 45 to 70% of
      patients who committed suicide presented depression. Suicide is the main
      complication of untreated depression. Patients who commit suicide take the more
      easily available medications. The decrease in the prescription of barbiturates
      has been associated with a decrease of the frequency of self-poisoning with
      barbiturates. In the same time, neuroleptics, antidepressants and benzodiazpines,
      more often prescribed, induced more lethality by suicide. The number of deaths by
      millions of prescriptions variates, with the antidepressants, between 13 and 166.
      They correspond to 0.005% of death each year among patients taking
      antidepressants. In daily practice, the prescription of antidepressants, which
      alleviates depressive symptoms, usually prevents suicidal risk among depressives.
      In some rare cases, antidepressants and other psychoactive agents are used by the
      patients, in overdosage, to commit suicide. According to the results of all
      controlled studies of antidepressants, suicide attempts are more frequent among
      patients taking antidepressants (1.7% of the cases) than among patients receiving
      placebo (0.8%). These data may be related to methodological bias which are
      discussed here. They do not initiate to restrain the prescription of
      antidepressants to depressed patients but to provide more frequent consultations
      and even to hospitalize depressives at high risk for suicide.

PMID- 9138937
TI  - [Psychological autopsies in the study of suicide].
AB  - Psychological autopsies represent an essential method in the study of suicide and
      its determinisms. They are difficult to realize but a growing number of them have
      shown that a large majority of the suicide victims were suffering from mental
      disorders. Many of them had seen a doctor in the days or weeks preceding the
      suicide.

PMID- 9138939
TI  - [Panic, Attack and Disorder. Proceedings of a symposium. Paris, France, September
      7, 1996].

PMID- 9138940
TI  - [Panic attack: viewpoint of the internist].
AB  - The first part of this paper presents the history of a panic attack occurring
      during an acute hypertensive crisis, which led to the discovery of a left adrenal
      phaeochromocytoma. The second part of the paper presents a discussion of
      conditions that can simulate panic attacks. Accounts are given of: acute
      hypertensive crises, the post-ictal phase of epilepsy, overt tetany, certain
      forms of hypercalcaemia, hyperventilation syndromes, and lastly, paroxysmal
      dysrhythmias. The third part of the paper discusses panic reactions occurring in
      a variety of clinical conditions, in particular, once again, hypertensive
      attacks, profuse external haemorrhage, dyspnoeic attacks and hypoglycaemic
      attacks. These different manifestations demonstrate that failure to recognise a
      clinical sub-stratum responsible for, or co-existing with, a panic attack leads
      to the risk that treatment of a neuro-psychological nature may be inappropriate.

PMID- 9138938
TI  - [Views from Dordogne, and the moon, on suicide].
AB  - Death-rate by suicide in Dordogne, department of Aquitaine (France), remains
      above the national average: 25.4 for 100000 inhabitants in Dordogne per year
      between 1990 and 1993, against 20.4 in France between 1989 and 1991. They are
      mostly old peasants of the west and the north of the department, and rural people
      in their thirties, who kill themselves. But the frightful high rate of suicides
      registered from 1975 to 1985 (31.8 in Dordogne between 1980 and 1982, against
      25.3 in France for the same period), and which hit mostly young adults and the
      population around the town of Nontron, appears reduced. These suicides express,
      under the pressure of contemporary upset of the occidental society, the old
      crisis of abandonment of the rural areas in crispation. The most fragile succumb-
      and not only in the Perigord. Moreover, the suicides are here more important in
      September and in January. The sociological explanation of G. Masterton (1991) is
      plausible. The rates of suicides are also studied according to the lunar months.
      In Dordogne, the maximum and minimum rates of suicides are situated every year in
      two consecutive lunar phases. Further, these values are scheduled from one year
      to another, alternatively in the ascending period of the moon and then, in the
      descending period. Lastly, mathematic analysis of the suicides registered in the
      whole of 4 similar french departments (stepped according their latitude), during
      2 years (1991-1992) and at the time of the first 3 days of each lunar phase,
      reveals that their rate is significantly lower in Full Moon than in the First
      Quarter period; this is equally true in the department of Maine and Loire.
      Further, Ph. Brosseau had shown (1987) that the French dies less in Full Moon,
      and more in New Moon period. The Full Moon period seems to protect the fragile
      subjects against their own death.

PMID- 9138941
TI  - [Panic disorder and panic attack].
AB  - Panic disorder first appeared as a specific diagnostic entity in 1980, in the
      third Edition of "Diagnostic and Statistical Manual of Mental Disorders" (DSM
      III). The classical anxiety neurosis was divided into two separate entities:
      panic disorder and generalized anxiety disorder, whose major criteria for
      distinction was based, in a simplified manner, on the presence or absence of
      panic attacks in the patient's history. Validity of the concept of panic disorder
      as a clinical and autonomous entity is now widely accepted. It is based on
      numerous epidemiological, phenomenological, biological, genetic and therapeutic
      studies that have established, that panic disorder may be clearly distinguished
      from other anxiety and mood disorders. However, this disorder still has unknown
      aetiology and criteria for definition remain purely clinical. Controversies as
      regards the validity of diagnostic criteria for panic disorders may account for
      its successive definitions in the DSM III-R, then in the DSM IV. In fact, in
      contrast to the definition of panic attacks that has remained practically
      constant, panic disorder was initially defined by the recurrence of panic
      attacks. It is now considered by the authors of the DSM IV as a disorder
      characterized by a chronic anxiety, focused on the risk for panic attacks showing
      symptoms evocative of autonomic dysregulation. In the DSM IV, panic attack is now
      considered as a syndrome which is not specific for panic disorder. Panic disorder
      may be diagnosed in a patient who has suffered from recurrent panic attacks,
      provided that one at least of the latter have been associated with one of the
      following symptoms: persisting fear from other panic attacks; concerns about
      possible implications of panic attacks or their consequences; major behavioural
      changes related to the attacks. Evolving positions of the successive authors of
      the DSM contrast with more conservative attitudes of the authors of the CIM 10,
      who still consider agoraphobia as a key symptom. Whatever the issues of these
      definitions, it must be kept in mind that panic disorder is a severe syndrome,
      and leads to major suffering and significant impairment of the patients' quality
      of life as well as their social life and interpersonal relationships. Comorbidity
      with depressive and addictive disorders is frequent, and panic disorder is
      considered by numerous authors as a risk factor for suicide. Due to the severity
      of panic disorder, its frequency and the fact that it is too often undiagnosed
      (although there are effective therapeutic strategies), efforts are fully
      warranted, so that patients may benefit from early diagnosis and adequate
      treatment.

PMID- 9138942
TI  - [Panic attack and panic disorder in the child and adolescent].
AB  - In the light of the current interest in the development of this disorder in
      adults, a number of recent studies have been devoted to the condition in children
      and adolescents. These papers include retrospective studies of adults suffering
      from the disorder, clinical reports on children or adolescents with the same
      problems, epidemiological studies of children and adolescents consulting
      psychiatrists, epidemiological studies of the general population, family studies,
      and studies of chemotherapeutic treatments. The conclusion from these papers is
      that many children and adolescents who present with physical symptoms are
      suffering from a panic disorder which has not been identified as such at the
      time. Other studies have analysed the age of onset of the first attack. All these
      studies are now in agreement in confirming that adolescence is the preferential
      age of onset of panic disorder. There even appears to be a correlation between
      the stages of puberty (Tanner) and the onset of panic attacks in young
      adolescents. At each successive stage of puberty, C. Hayward et al. (1992) found
      a progressively higher rate of panic attacks. "Panic disorder" thus
      preferentially develops in adolescence, more commonly in girls than boys,
      particularly in subjects who are prone to anxiety or show traits of the "avoiding
      personality", but who also have a depressive tendency. A number of studies also
      suggest that pathological separation anxiety developing in childhood represents a
      risk factor for the development of "panic disorder" and/or agoraphobia during
      adolescence or adult life. The natural history of Panic Disorder in adolescence
      is still little known. The greatest risk appears to be chronic anxiety, but the
      progressive establishment of panic disorder, its development in the direction of
      depressive disorder, and self-medication and/or abuse of psychotropic drugs, also
      give cause for concern. Finally, a number of psychopathological considerations
      have raised the possibility that the onset of a panic disorder may be a danger
      signal of an underlying depressive personality.

PMID- 9138943
TI  - [Epidemiology of panic disorder].
AB  - The prevalence of panic disorder in the general population is 2,3% over a
      person's whole life, and 0,5-1% per year. International studies have yielded more
      widely varying estimates of the prevalence of panic attacks (4-12%). The
      proportion of patients consulting their doctors for panic disorder is also highly
      variable; the frequency is a function of the medical specialty (being highly
      represented in cardiology and the emergency services). In psychiatry, panic
      disorder represents the main diagnosis in one patient out of 10 or 20. Panic
      disorder is more common in women than men, and in young or middle-aged subjects
      and those living alone (separated, widowed or divorced). In socio-economic terms,
      it is the socio-educational level rather than income or profession that appears
      to be the determining factor. Lastly, residence (urban/rural) and the fact of
      belonging to a particular socio-cultural group seem to play little part. As with
      many mental disorders, two predisposing factors have been found to operate: a
      genetic element, as shown by family and twin studies, and an element relating to
      psychoaffective development (traumatic events in childhood, separation anguish,
      etc.). Panic disorder is commonly associated as a comorbid trait with other
      neurotic and anxiety disorders, depression, alcoholism and drug abuse. These
      associations represent poor prognostic factors associated with chronicity,
      attempted suicide and social handicap. Prospective studies of overall outcome
      have shown complete remission rates of 10-20% at 3 or 5 years. However, if the
      occasional occurrence of a few panic attacks is regarded as acceptable, the
      prognosis can be regarded as good for two-thirds of affected subjects.

PMID- 9138944
TI  - [Panic: attack and disorder. History of the word and concepts].
AB  - The history of the word panic, of the concepts of Panic attack and of Panic
      Disorder is a complex one. The adjective word panic, derived from the Greek,
      stressed initially the intensity of a feeling of unjustified, individual or
      collective, fear, similar to the reaction provoked, according to the mythology,
      by the intervention of the God Pan. In their present meanings, the concepts
      belong to the group of anxiety states, the Panic attack being a symptom
      characterized by a paroxysmal anxiety which may appear in various
      psychopathological states, whereas the Panic Disorder is a nosological category
      whose diagnostic criterium is the appearance, with a definite frequency, of Panic
      attacks. The disorder is frequently associated to agoraphobia considered, when it
      exists, as a complication. It is necessary to describe, in addition to the terms
      and concepts related to panic, the history of the terms angoisse and anxiete (and
      of the equivalent ones in English and German, since many studies dealing with the
      subject have been written in those languages) and the history of agoraphobia. The
      history of the word panic and of the psychiatric concepts to which it is applied
      today are partially different as are the current meanings of the adjective and
      the substantive (and today of the verb to panic) from their technical meanings.
      In the technical vocabulary the substantive word refers on the one side to an
      abnormal group behaviour whose mechanisms, when it appears in an army by also
      elsewhere, are studied by social psychopathology. On the other side it has been
      used until recently, but only in psychiatric texts written in English, for
      describing acute individual states of high anxiety, eventually associated with
      other symptoms, and considered as pertaining-in contrast to the Panic attack in
      its present meaning-to various psychiatric illnesses (melancholic panic,
      homosexual panic). A description of states similar in their aspects, including
      the association to agoraphobia, to the present Panic attack, may be found in the
      literature of the XIXth century. Essential in this respect is the description of
      anxiety neurosis which Freud isolated in 1895 from neurasthenia and defined by
      the coexistence of a state of moderate and permanent anxiety and of anxiety
      attacks, whose manifestations were identical to those of the present Panic
      attack. Under the influence of Klein's researches which, from 1962 on,
      demonstrated the differential reactivity to drug therapy of its two component
      parts, anxiety neurosis was divided in two distinct entities. The term Panic
      attack-for reasons given in detail by the paper-was proposed for the acute
      anxiety attack, whereas the state of moderate and permanent anxiety, considered
      as a completely independent disorder, received the name of Generalized Anxiety
      Disorder. The concept, with its corresponding nomenclature, was adopted initially
      in the United States by the RDC (1975), then by the DSM-III (1980). It is
      accepted today and has been the source of a large number of investigations about
      its semiological, nosological, epidemiological, etio-pathogenic and therapeutic
      aspects which fall outside of the scope of this paper.

PMID- 9138945
TI  - [From inducers of panic attack to neurobiology of panic disorder].
AB  - Various provocative agents, including sodium lactate, carbon dioxide (CO2),
      caffeine, yohimbine and cholecystokinin (CCK), have been utilized as panicogenics
      in studies on healthy volunteers as well as in panic disorder patients. Most
      provocative agents are lacking in specificity, limiting their use in identifying
      neurotransmitter systems involved in panic attacks. CCK appears to offer several
      advantages over other challenge strategies since it is a putative
      neurotransmitter in the CNS, with its own neuronal pathways and receptors, and
      reliably provokes panic attacks in a dose-dependent manner. It is important to
      clarify the relationships between CCK and other neurotransmitter systems in order
      to further understand the neurobiology of panic disorder. The possible roles of
      some of these neurotransmitters in panic disorder are discussed in this review.

PMID- 9138946
TI  - [Ethology of panic disorders].
AB  - Animal's world is perfectly coded. According to genetical equipment, there are in
      natural sphere, signals whose bio-physical structure releases panics behaviours.
      But the mere fact that an organism is developing from birth to death makes it
      sensitive to different informations. Imprinting allows to young to incorporate
      another live-being or a sphere, category it. From now, if we change this sphere,
      it's a trouble of relation of world which panics the young. Surpopulation
      regarded in an animal world as an impossibility to classify its world, impairs
      animal's behaviours and released accidental panics. Overgenerational appears soon
      in animals, a long time before words. But when human language appears, it
      modifies memory's nature and allows therefore troubles released by a
      representation. The tranquilizing mechanism often consists of changing fear in
      anxiety, easier to manage.

PMID- 9138947
TI  - [Pharmacotherapy of panic disorder].
AB  - The concept of Panic Disorders has itself been developed on the strength of
      therapeutic effects of drug treatments and it is therefore not surprising that
      psychotropic medications are currently the main therapeutic tool for this
      condition. Their use may be indicated in two differing circumstances, as
      treatment for Panic Attack itself or as a long-term treatment for what is
      properly called Panic Disorder. The latter scenario is that which has been most
      actively studied and represents the more original side of the question. Treatment
      of acute Panic Attack involves administration of sedative anxiolytics,
      principally benzodiazepines (BZD). Long-term treatment aiming to prevent repeated
      attacks is the core strategy for treatment for Panic Disorder. For the past
      fifteen years, a large number of research projects have shown the elective anti
      panic efficacy of a number of drugs, principally antidepressants and anxiolytics.
      The response profile to anti-depressant treatment is characterized by a lag time
      which is sometimes longer than that observed when they are used solely as
      antidepressants; frequently they are also less well tolerated which necessitates
      a very gradual step-up in dosage. The "classic" MAOI (non-selective and
      irreversible) have a proven anti-panic effect. Selective serotonin reuptake
      inhibitor (SSRI) anti-depressants are currently drugs of choice in the treatment
      of Panic Disorder. Although the anti-panic effect appears to be common to all the
      various SSRI drugs available, and directly attributable to their mechanism of
      action, not all of them however have undergone controlled studies. In France,
      paroxetine is the first anti-depressant in this group to obtain a marketing
      authorization for this particular indication. The advantages of the SSRI drugs
      are principally related to their limited adverse effects and lack of toxicity,
      thereby making them particularly straightforward to use. Benzodiazepines (BZD)
      are the second group of psychotropic medications which have been shown to be
      effective in the treatment of Panic Disorder. The major disadvantage of the BZD
      for this indication is chiefly related to the major risk of promoting a
      dependency state with the corresponding appearance of a withdrawal syndrome when
      treatment is stopped. This risk constitutes a major stumbling block to the use of
      BZD as a first-line treatment for Panic Disorder. Various other drugs have been
      evaluated in the treatment of Panic Disorder with varying success. The current
      anti-panic pharmacopoeia therefore appears to be relatively well stocked. In this
      context, antidepressants-especially the SSRI drugs-are the first-line treatment
      of choice for Panic Disorders. In all cases, it appears useful to integrate
      pharmacological treatment within an overall management plan for the patient with
      Panic Disorder, especially if it is hoped to maintain therapeutic benefit long
      term.

PMID- 9138948
TI  - [The role of psychotherapy in managing panic disorder].
AB  - This general presentation reviews briefly the various psychotherapies proposed
      for panic attacks and agoraphobia treatment. Cognitive-behaviour therapy (CBT) is
      the only validated therapy. Behavioural model of agoraphobia and cognitive model
      of panic attacks are detailed. The main techniques are described. The results of
      controlled studies and meta-analyses demonstrate that CBT represents an
      alternative to anxiolytics and antidepressants. CBT is a brief form of therapy
      (10-20 sessions) which has been compared with waiting list, placebo, relaxation,
      antidepressants, anxiolytics or supportive therapy. Four meta-analyses agree on
      that in vivo exposure is a core element of the treatment of panic attacks and
      agoraphobia. They demonstrate also that agoraphobia is more difficult to treat
      than panic attacks in which placebo effect is quite powerful. Cognitive therapy
      centered on panic attacks demonstrated a significant effectiveness in controlled
      studies. CBT facilitates benzodiazepines withdrawal. Combination of in vivo
      exposure with high doses of benzodiazepines is counter-productive in the long
      term. Controlled studies are favorable to the combination of CBT with imipramine,
      SSRI (paroxetine, fluvoxamine) or buspirone. But the positive effects of these
      combinations are only found in the short term. CBT possesses the advantage of
      stable long term effects.

PMID- 9138949
TI  - [Fictional anxiety in detective literature and motion pictures].

PMID- 9138950
TI  - [Paroxysmal anxiety crisis, viewpoint of the general practitioner].
AB  - According to general practitioners, anxiety disorders are amongst the commonest
      complaints in primary care. A survey carried out by reseau Sentinelle in June
      1995 showed that acute panic attacks in general practice have given rise to
      300,000 hours of consultations per year by general practitioners in France.
      Positive diagnosis raises practical difficulties in the surgery or at home, GPs
      could avoid such difficulties by using diagnosis criteria based on DSM IV and
      having knowledge of the patient's anticipation anxiety. In order to make the
      differential diagnosis, GPs will need to rule out any organic cause, notably
      cardiovascular pathology. Prior acquaintance with the patient will be of great
      help. A decision to treat is based on the frequency of acute panic attacks and on
      exchange of information with the psychiatrist. In return, the specialist will
      assist the GP in managing the patient's condition.

PMID- 9138951
TI  - Proceedings of the 11th European Association of Gynaecologists and Obstetricians
      Congress. Budapest, Hungary, 19-21 June 1996.

PMID- 9138952
TI  - Folates and the fetus.
AB  - It is proven that folic acid supplied in the periconceptional period can lower
      the recurrence and occurrence rate of neural tube defects (NTDs). Our research
      team on prevention of birth defects could demonstrate that folic acid preventable
      NTDs are partly based on hyperhomocystinemia and a genetic predisposition
      (mutation of the methylenetetrahydrofolate-reductase gene (MTHF-R)). Reduced
      activity of the folate methylation cycle seems to be an attractive working
      hypothesis in the aetiology of NTDs. This genetic metabolic defect can be
      overcome by treatment with folic acid and/or vitamin B12.

PMID- 9138953
TI  - Infertility evaluation and treatment according to Jewish law.
AB  - The Jewish attitude toward infertility can be learned from the fact that the
      first commandment of God to Adam was "be fruitful and multiply". When evaluating
      an infertile couple according to the Halakha (Hebrew law), one should first
      evaluate the female factor. If pathology is found, one may proceed to investigate
      the male factor, inadequate or abnormal production, ejaculation, or deposition of
      spermatozoa. The basic fact that allows in vitro fertilization (IVF) and embryo
      transfer (ET) to be considered in the rabbinical literature at all is that the
      oocyte and the sperm originate from the wife and the husband, respectively. For
      many centuries Jewish religious authorities have discussed the principle involved
      in artificial insemination from a donor. The discussions are based on ancient
      sources in the Talmud and the codes of Jewish law is prohibited for a variety of
      reasons e.g. incest, lack of genealogy, and the problem of inheritance. In the
      case of egg donation the problem that arises is who should be considered the
      mother, the donor of the oocyte or the one in whose uterus the embryo develops,
      the one who gives birth. Jewish law states that the child is related to the woman
      who finished its formation, the one who gave birth. The Jewish religion does not
      forbid the practice of surrogate motherhood in the case of full surrogacy. From
      the religious point of view, the child will belong to the father who gave the
      sperm and to the woman who gave birth. Creating and inducing a preimplantation in
      embryo in vitro for fertility research should be allowed if there is a real
      chance that the sperm owner may benefit and have a child as a result of this
      research. Nowadays, assisted reproductive technology is a common practice in the
      treatment of infertility. Nevertheless, different religious arguments of the
      world's religions impose limitations on the therapeutic approach to infertility.

PMID- 9138954
TI  - In search of human dignity: reproductive health and healthy aging.

PMID- 9138955
TI  - Intraamniotic surfactant for prevention of neonatal respiratory distress syndrome
      (IRDS): rationale and personal experience.
AB  - OBJECTIVE: To evaluate the efficacy of intramniotic instillation of supplementary
      surfactant for the prophylaxis of neonatal IRDS in an emergency obstetric
      setting. STUDY DESIGN: Supplementary natural surfactant (SS) was administered
      intra-amniotically (80 mg in 1 ml) under ultrasound guidance in the proximity of
      the fetal nostrils and mouth in six pregnant women at 24-32 weeks gestation, with
      immature amniotic fluid indices of fetal lung maturity, and whose delivery was
      imminent because of severe fetal distress, deteriorating maternal conditions, or
      refractory vaginal bleeding. The administration of SS was preceded by IV
      aminophylline to the mother (a bolus of 240 mg over 10 min, and a maintenance
      dose of 0.02-0.1 mg kg-1 min-1) in order to elicit sustained fetal breathing
      movements. RESULTS: The clinical conditions of the six newborn infants were good
      with no respiratory problems in four cases, and with mild IRDS in the remaining
      two, which, however, resolved uneventfully. CONCLUSIONS: It is suggested that
      this prophylactic approach has a great potential for becoming a reliable option
      for the antenatal prevention of IRDS.

PMID- 9138956
TI  - Rupture of the membranes and postpartum infection.
AB  - The greatest risk of preterm prelabour rupture of membranes (PPROM) is preterm
      delivery. According to the Perinatal Information System of Slovenia there were
      5.92% preterm deliveries in 1994. We studied 809 deliveries of less than 34 weeks
      of gestation in the Ljubljana Maternity, from 1992 to 1994; 33.7% of these
      started with PPROM. Risk factors for PPROM were conization, cerclage and use of
      antibiotics for any reason in current pregnancy. Amnionitis and febrile illness
      during labour increased with longer duration of PPROM but maternal postpartum
      infections did not. In neonates, more cases of lower Apgar scores after 1 and 5
      min and more cases of suspected sepsis were found with the increased duration of
      PPROM. In Slovenia, with good facilities for transport in utero and good neonatal
      care, after PPROM it is best to transport the pregnant women to the third level
      center and then wait until labour starts or to recur to prompt delivery when
      maternal or fetal signs so require. From 1987 to 1993 there were 159264
      deliveries in gestations equal to or over 34 weeks; 20.8% started with PROM. In
      our observational study we found the best results when labour was induced. There
      are, however, many disagreements about the management of (P)PROM.

PMID- 9138957
TI  - A combined Doppler and morphopathological study of ovarian tumors.
AB  - OBJECTIVE: To evaluate intratumoral blood flow in 46 patients with ovarian
      masses. METHODS: Transvaginal color Doppler was carried out in each patient prior
      to the laparoscopy or laparotomy. Tumors were analyzed according to the size,
      morphology, presence of the neovascularization, configuration and distribution of
      the tumoral blood vessels and pattern of the intratumoral blood flow. Vascular
      patterns of surgically removed tumors were studied microscopically. Three types
      of vasculature were analyzed: neovascular capillaries without media, sinusoidal
      thin walled spaces and normal vessels' morphology. The RI (resistance index)
      values were analyzed in relation to gross appearance, histological type of the
      tumor, existence of inflammation/necrosis area and vascularization pattern of the
      tumor. RESULTS: Neovascularization was found in all the malignant tumors with low
      RI (less than 0.42) and solid or solid cystic gross morphology. Neovascular
      signals were obtained in only one patient with ovarian endometrioma. Sinusoidal
      spaces were identified in all the malignant ovarian tumors, but also in most of
      the benign lesions. Normal vessel morphology was identified in 60% of malignant
      ovarian tumors and in all the patients with benign ovarian lesions. CONCLUSION:
      There is a significant correlation between Doppler and histopathological studies
      in terms of vascularization pattern analysis (detection of neovascular
      capillaries, sinusoidal spaces and normal vessels morphology). In most of the
      malignant ovarian tumors there were few areas of vascularization which can be
      analyzed non-invasively by transvaginal color and pulsed Doppler ultrasound.

PMID- 9138958
TI  - The assessment of uterine and ovarian perfusion in infertile patients.
AB  - OBJECTIVE: To evaluate ovarian and uterine perfusion in 790 infertile patients.
      STUDY DESIGN: Transvaginal color Doppler assessment of the ovarian and uterine
      circulation in infertile patients with benign pelvic lesions, uterine anomalies
      and ovarian or uterine dysfunction. RESULTS: Uterine anomalies were detected in
      146 patients: 135 septate and 11 bicornute uteri. No alteration, in terms of
      resistance index (RI), was detected for main uterine arteries in patients with
      duplication anomalies of the uterus. Submucous fibroids were identified in 25
      patients, while subserous leiomyoma were diagnosed in five patients. The mean RI
      for these lesions covered the value of 0.55 +/- 0.09. Endometrial polyps altered
      the endometrial perfusion in 26 infertile patients (RI = 0.48 +/- 0.06), while 11
      avascular intrauterine synechiae were identified. Functional ovarian cysts were
      transitory present in 59 patients. The RI varied from 0.52 +/- 0.06 for
      follicular and 0.46 +/- 0.08 for corpus luteum cysts. Ovarian endometrioma were
      visualized in 78 infertile patients. Forty eight of them were vascularized at the
      level of the hilus, while 16 showed pericistic vascular location (RI ranged from
      0.40 to 0.59). Dermoid cysts (n = 12) were mostly avascularized (75%), while
      polycystic ovaries demonstrated increased intraovarian vascularity in all the
      examined cases. The mean RI detected within the ovarian stroma was 0.52 +/- 0.06.
      In 11 patients premature menopause was predicted due to low volume of the ovary
      (< 2 cm3) and absence of the intraovarian vascularity. Hydrosalpynx or
      sactosalpynx were imaged in 154 patients. The RI varied from 0.44 in acute to
      0.74 in chronic stage of the disease. CONCLUSION: Transvaginal color Doppler
      allows precise estimation of the functional state of the reproductive organs in
      infertile patients.

PMID- 9138959
TI  - Management of the menopause and HRT by ultrasound.
AB  - Recent improvement of the transvaginal grey-scale and colour Doppler ultrasound
      scanning permits to investigate the morphology and the perfusion parameters of
      the female pelvic organs in the menopause. Data from detailed scanning of the
      ovaries and the uterus reflect the hormonal status, but the menopausal age from
      the last menstrual bleeding (LMB) and the sequence of the HRT given must be taken
      into consideration. Screening for endometrial pathology is advisable in the days
      after the withdrawal bleeding in women taking HRT. The positive vascular changes
      and increased peripheral perfusion in women with HRT detected by Doppler
      ultrasound are due to the oestrogen's vasodilator effect, which leads to
      cardiovascular and cerebrovascular protection. Changes of the uterine perfusion
      during the combined sequential HRT cycle doesn't seem to reflect the reverse
      effect of the progestin to oestrogen on the general vasculature, but correlates
      to the vascular changes of the normal menstrual cycle. The disappearing uterine
      notch in the menopause suggests decreasing vessel compliance. In women taking HRT
      the uterine notch persists or even may reappear years after the LMB, as a sign of
      the vessel compliance reserve probably activated by oestrogen and may act also as
      an indicator of the effect of HRT on arterial status.

PMID- 9138960
TI  - Chaos theory and power spectrum analysis in computerized cardiotocography.
AB  - Power spectrum and chaos theory analysis, methods recently applied to fetal
      surveillance, may offer an effective tool for recognising fetal hypoxia and
      consequential collapse of fetal homeostasis earlier than at present. However,
      strict continuity and high precision of input data is an indispensable
      prerequisite. If one overlooks this requirement the results may be misleading.
      The aim of the present work was to find a method that provides strictly
      continuous and highly precise beat-to-beat FHR data values. It was found that
      only the determination of heart beat intervals between successive R peaks, using
      the digital FECG recording technique developed here, meets the necessary
      requirements for power spectrum and chaos theory analysis.

PMID- 9138961
TI  - HPV- and node status in cervical cancer long-term results.
AB  - OBJECTIVE: To evaluate prognostic significance of HPV-status in cervical cancer
      and to compare that with the prognostic significance of lymph-node status.
      METHODS: Cervical cancer biopsy specimens from primaries and, in surgical cases,
      from pelvic lymph-nodes too were analysed for the presence of human
      papillomavirus type 16 DNA-sequences using PCR technique. The management of
      surgical cases with two exceptions included Wertheim's hysterectomy predominantly
      with preoperative local radiotherapy and also with postoperative local and
      external beam radiotherapy depending on the histology. Non-surgical cases were
      treated with combined local and external radiotherapy to pelvic fields. RESULTS:
      Patients have been followed up for an average of 37 months after treatment
      ranging between 0 and 102 months. The mean progression-free survival time of
      surgical and non-surgical cases were 43 and 28 months, respectively. Patients
      with HPV-16 positive biopsies from the cervical primary had an average
      progression-free survival of 37 months, the same as those with HPV-16 negative
      cervical biopsies. Those patients who were found to carry HPV-16 DNA in their
      surgically removed pelvic lymph-nodes had an average of 27 months progression
      free survival. The mean progression-free survival among histologically node
      positive and node-negative surgical cases were 23 and 42 months, respectively.
      The mean progression-free survival time of node-positive cases with HPV-16
      positive cervical primary was 7.5 months while that of patients with HPV-16
      negative cervical biopsy was 38 months. Among histologically node-negative
      patients, HPV-16 positive and negative cases had an average progression-free
      survival time of 38 and 46 months, respectively. CONCLUSIONS: Among those under
      investigation the most important factors to predict progression-free survival
      were surgically amenable disease, histologically negative pelvic lymph-nodes and
      HPV-16 negative cervical biopsies, though this latter one proved significant only
      among surgical cases.

PMID- 9138962
TI  - Overexpression of the oncogene c-erbB-2 (HER2/neu) in ovarian cancer: a new
      prognostic factor.
AB  - Ovarian cancer is the leading cause of death in gynecological cancers. To date,
      there are no prognostic factors in ovarian cancer that adequately account for
      tumor biology and the course of the disease. In recent years, some reports have
      described the prognostic significance of the amplification and overexpression of
      the oncogene c-erbB-2 (HER2/neu) in various human cancers, including ovarian
      cancer. The c-erbB-2 proto-oncogene is located on the long arm of chromosome 17.
      It encodes a 185 kD transmembrane glycoprotein receptor (p185HER2) that has
      sequence similarities with the epidermal growth factor receptor (EGF-R). In
      ovarian cancer, the percentage of c-erbB-2 positive cases varies from 9 to 32%.
      Correlation with tumor stage and the degree of histological differentiation was
      not observed. The overexpression of c-erbB-2 is a new and statistically
      independent prognostic factor. The overexpression of oncogene c-erbB-2 in ovarian
      cancer can-be detected by immunohistochemistry staining for the protein p185 and
      characterizes a group with unfavorable tumor biology and a significantly worse
      prognosis. Elevated serum levels of the c-erbB-2 oncoprotein have been identified
      in patients with various cancers known to overexpress the c-erbB-2 oncogene. The
      detection of a p185 oncoprotein fragment in the sera of ovarian cancer patients
      was recently published by our group. Antiproliferative effects of monoclonal
      antibodies directed against p185 have been demonstrated in breast cancer
      patients. This may lead to a new approach in ovarian carcinoma therapy, too, over
      and above the diagnostic aspects.

PMID- 9138963
TI  - High-risk obstetrics, medicolegal problems.
AB  - The perinatal period is one of the most dangerous time of life. The
      responsibilities of the obstetricians are multifold. It is very difficult to draw
      a line between good and substandard care, therefore in perinatology and
      especially in high-risk obstetrical cases there are no absolute rules of
      management. The lay public is convinced through media channels, that modern
      reproductive research eliminated all the risks and hazards associated with
      childbirths, therefore only 100% healthy babies are accepted. Pregnancy is
      regarded as a 'success story' and if the baby is born with neurological defects
      (cerebral palsy) the parents and their advisors feel, that someone responsible
      for the defect should be found in the chain of management. This attitude starts a
      legal battle focusing on the events of labor and delivery. But in most cases it
      is very difficult to determine if a peripartal neonatal encephalopathy originated
      from the time period of labor and delivery, or started weeks earlier during
      pregnancy as an unnoticed event. Perinatal morbidity indicators are best based on
      neonatal clinical signs, which are predictive of later morbidity of the child.
      Neonatal seizures within 48 h of delivery of the baby could be a good index of
      later morbidity.

PMID- 9138964
TI  - Hormone replacement therapy and prevention of osteoporosis: risk assessment and
      practical advice.
AB  - A review of the Debrecen Regional Osteoporosis Program (DROP) in Hungary is
      given, with special reference to the detection of postmenopausal osteoporosis
      (PMOP) and its treatment by hormone replacement therapy (HRT). The new definition
      of osteoporosis by focusing on bone mineral density (BMD) measurements has the
      major advantage of practical usefulness. The algorithm of managing osteoporotic
      patients can be easily constructed from the result of bone densitometry as the
      primary diagnostic tool. The DROP serves a total population of 550,000, is
      equipped with a DXA bone densitometer, a bone metabolism laboratory and backed by
      a multidisciplinary team of clinicians from gynecology, radiology, rheumatology,
      internal medicine, and orthopedic surgery. In 1995 the total number of patients
      undergoing densitometry was 3170. In 2045 patients T scores of -1 or below were
      found. From this total number, 348 patients received HRT for 1 year or longer.
      The results of the treatment showed a positive response (i.e. no bone loss, or
      net gain) in 65%, while half of the 'non responders' proved in fact non
      compliant. The contradiction between risk assessment and early diagnosis is
      explained and replacing 'risk assessment' by 'selection criteria for bone
      densitometry' is proposed. 'Prevention of osteoporosis' is also to be replaced by
      'prevention of complications', i.e. osteoporotic fractures. One of these measures
      is HRT. Its rational use in the prevention and treatment of osteoporosis and its
      relation to other treatment methods in the authors' own experience is discussed.

PMID- 9138965
TI  - Hormone replacement therapy and cardioprotection: basic concepts and clinical
      considerations.
AB  - A large body of epidemiological evidence shows that estrogen use after the
      menopause reduces the incidence of cardiovascular disease up to 50%. The use of
      progestin as co-medication in HRT appears not to attenuate the cardioprotective
      effects of estrogen. Menopause-related changes in metabolic cardiovascular risk
      factors are identifiable, as are HRT-related changes in these factors. Estrogens
      may act in a gender-specific way on vascular endothelial cells and other
      components of the vessel wall enhancing the synthesis and release of NO and other
      vasodilators and by inhibiting the synthesis and release of vasoconstricting
      agents, thus favoring vasodilation. Angiographic studies demonstrated in
      postmenopausal women with ischemic heart disease a reduction in coronary stenosis
      by estrogen monotherapy. Several studies, including the PEPI-trial, failed to
      demonstrate any major effect of HRT on blood pressure. The information on HRT and
      cardioprotection which is available so far is very promising and merits
      recommending HRT not only in healthy women but also in women with cardiovascular
      disease as well as in women with increased risk for this disease.

PMID- 9138966
TI  - Hormone replacement therapy and breast cancer morbidity, mortality and
      recurrence.
AB  - The effects of short-term and long-term HRT (in its various forms, unopposed
      oestrogens, sequentially combined HRT and continuous combined HRT) on the female
      breast are reviewed. The question is addressed whether HRT will increase the risk
      of breast cancer as well as the risk of dying from breast cancer in healthy
      women, and whether or not women who already run an increased risk on the basis of
      a positive family history, use of DES during pregnancy or because of the presence
      of premalignant epithelial abnormalities in the breast, increase their risk for
      breast cancer further. The risks of HRT and the options for HRT in patients who
      have a history of breast cancer are discussed and alternative treatment
      modalities for climacteric complaints (e.g. clonidine, paced-respiration) or for
      preventive HRT (e.g. tamoxifen, tibolone) are reviewed.

PMID- 9138967
TI  - HRT and breast cancer risk, what to advise?
AB  - Breast cancer is the major malignancy among women in Western countries and
      constitutes approximately 25% of all female cancers. There is epidemiological
      evidence that reproductive factors and reproductive hormones are important for
      incidence as well as individual risk. Unfortunately the potential public health
      benefits of HRT have not been realised largely because of the fear of breast
      cancer. Epidemiological studies are conflicting but several reviews do suggest a
      moderately increased risk of breast cancer in long term current users of HRT. In
      clinical practice beneficial effects of long term HRT on women's health must be
      weighed against this background. The risk for adverse effects during a treatment
      during a period say 6-8 years is known to be very low. There is no indication for
      progestogen addition in women without a uterus. In most women with risk factors
      of osteoporosis, benefits from long term HRT apparently outweighs other possible
      risks. Individual asymptomatic women without any specific risk factors may well
      receive HRT after individual information but general recommendations for
      treatment of all asymptomatic women are currently not justified.

PMID- 9138968
TI  - Prognostic factors in cervical cancer.
AB  - The inadequacy of clinical methods has spurred efforts to develop objective,
      measurable and reproducible parameters for the spread and growth behaviour of
      cervical cancer. Morphological methods were applied first. They can be used only
      on the surgical specimen, but are accessible to biometry. The presented results
      are based on 479 surgical specimens obtained at radical abdominal hysterectomy
      for cervical cancers of different sizes. The specimens were processed as frontal
      giant sections with the cervix, the vaginal cuff and the parametria on both
      sides. The median follow-up time was 7-8 years. Statistical correlations were
      found between follow-up data, biometric morphologic criteria and survival. The
      statistical ranking of the significant prognostic factors produced the following
      order: lymph node metastases, size of lymph node metastases, tumour volume,
      parametrial involvement and vascular invasion.

PMID- 9138969
TI  - The pubertal spurt: effects of sex steroids on growth hormone and insulin-like
      growth factor I.
AB  - In puberty, the growth spurt and the appearance of secondary sex characteristics
      occur concomitantly with an increase of sex steroids, growth hormone (GH) and
      insulin-like growth factor I (IGF-I). A number of experiments indicate that sex
      steroids exert a stimulatory action on the somatotropic axis. This effect is due
      to an amplifying action of oestradiol (secreted by the ovaries or after
      testosterone aromatization) on the neuroendocrine regulation of pulsatile GH
      release.

PMID- 9138970
TI  - Uterine surgery by operative hysteroscopy.
AB  - Uterine anomalies are found in 10-15% of women with repeated pregnancy loss.
      Uterine malformations and benign tumors are common causes of abortions, premature
      labour and abnormal fetal presentation in some cases. One-third of patients with
      habitual abortion have a septated or subseptated uterus, and two-thirds of
      pregnancies in women with duplicated uterus progress to term. Mullerian fusion
      defects and submucous fibroid may cause poor implantation or ineffective maternal
      blood supply to the placental site of the developing pregnancy. When these
      abnormalities were evaluated in infertile patients or in habitual abortions,
      traditionally the abdominal correction (Jones, Strassman, Tompkins etc.) were
      used traditionally. These procedures require incision of abdominal and uterine
      walls in general anesthesia with relative long hospitalization and recovery. The
      new endoscopic procedure; hysteroscopy is used not only to evaluate the type and
      size of Mullerian fusion defects but also to treat this malformation. The uterine
      septum is transsectable, via this elegant method, without injury of abdominal
      wall and healthy uterine wall musculature. After a traditional abdominal
      metroplasty there is no other-choice other than the cesarean section to prevent
      rupture of the uterus, but after hysteroscopic septotomy the vaginal delivery is
      possible and the uterine rupture rarity.

PMID- 9138971
TI  - Internal and external measures of quality assurance in gynecological surgery.
AB  - In the light of exploding costs in health care and increasing demands for public
      accountability, gynecological surgeons are forced to improve the effectiveness
      and efficiency of their care in order to increase the satisfaction of their
      'clients'. To do so, the implementation of a structured quality management system
      in gynecological care units is strongly encouraged. Basic requirements for an
      efficient quality management system comprise developing appropriate structures
      for the system, training staff in management techniques and using tools to
      monitor the quality of care. An important part of a quality management system is
      structured data collection permitting regional benchmarking between hospitals.
      The study 'Quality assurance in gynecological surgery' of the German Society of
      Gynecology and Obstetrics is mentioned as an example of such an external measure.
      Profiles help gynecological care units to recognize problem areas of their care.
      A list of further structural characteristics of a quality-oriented gynecological
      care unit, such as second opinion techniques or the application of clinical
      practice guidelines, is given to enable the evaluation or certification of
      quality management systems in gynecological departments.

PMID- 9138972
TI  - An evaluation of risk factors for in-patient falls in acute and rehabilitation
      elderly care wards.
AB  - Falls occurring in elderly in-patients during periods of hospitalization are
      common, and attempts have been made to predict and prevent them based on risk
      factor analysis. These have not looked extensively at specific elderly care
      wards. We have investigated in-patient falls in mixed acute and rehabilitation
      elderly care wards in a case-controlled study. Fifty fallers were paired with
      fifty non-fallers, and their risk factors for falling evaluated. Only three risk
      factors were significantly more common in the fallers. These were: a previous
      history of falls; the presence of confusion/disorientation, and needing help to
      toilet/incontinence/diarrhoea. Prediction of falls based on the presence of the
      first two of these risk factors gives a sensitivity of 68% and a specificity of
      88%. A risk factor approach to the prediction of falls in an in-patient elderly
      care setting seems to be less practical than was previously hoped.

PMID- 9138973
TI  - Relationship between falls and stride length variability in senile dementia of
      the Alzheimer type.
AB  - In this study, 97 patients with senile dementia of the Alzheimer type (SDAT) in a
      nursing home were followed over a period of 2 years, and the relationship between
      falls and gait function was examined. The findings indicated that the number of
      fallers was significantly higher in moderate-stage SDAT patients than in the mild
      stage patients. In the moderate-stage SDAT patients, walking speed and stride
      length, measured as indices to evaluate gait function, were significantly lower,
      and the stride length variability was significantly higher than in mild-stage
      patients. When comparing the gait indices of fallers and non-fallers by the
      severity of dementia, a significant difference was observed only in stride length
      variability. The gait abnormality associated with advanced severity in dementia
      is believed to be a factor affecting falling. In particular, stride length
      variability appeared to be an effective predictor of falling.

PMID- 9138974
TI  - Strength and muscle mass changes in elderly men following maximal isokinetic
      training.
AB  - The purpose of this study was to determine the effects of a maximal isokinetic
      training program on strength and muscle mass in a group of untrained men 73 +/-
      7.3 (range 68-82) years of age. Testing and training were conducted on an
      isokinetic dynamometer. Training consisted of one set of six maximal knee flexion
      and extension movements at 60 deg*s(-1) performed three times per week for 12
      weeks. The subjects trained the right leg only, the left leg serving as a within
      subject control. Trained leg peak torque increased by 18.1% for knee extension
      (from 107.2 +/- 42.9 to 126.6 +/- 44.6 Nm; p < 0.05) and by 18.2% for knee
      flexion (from 85.1 +/- 21.1 to 100.4 + or - 25.5 Nm; p < 0.05). Urinary
      creatinine levels increased by 24.3% (NS). We conclude that maximal isokinetic
      training at 60 deg*s(-1) increases strength and a urinary index of muscle mass in
      a group of aged untrained men.

PMID- 9138975
TI  - Asthma in the elderly patient.
AB  - Asthma is common in old age and carries significant morbidity and mortality. Most
      deaths due to asthma occur in old people. Often the diagnosis of asthma is
      overshadowed by other medical problems such as heart failure and emphysema, and
      thus elderly people may not receive optimal treatment. The treatment of an
      elderly patient with asthma is further complicated by concomitant disease and
      pharmacological interactions.

PMID- 9138976
TI  - Changes in lymphocyte subsets, interleukin 2, and soluble interleukin 2 receptor
      in old and very old age.
AB  - In this study, the changes in some of the cellular components of the immune
      system and the activity of the cytokine interleukin 2, important for immune
      activation and lymphocyte proliferation, were measured in a large cross-sectional
      study of all age groups including octogenarian and nonagenarian subjects. In 206
      apparently well community-living subjects, the absolute lymphocyte count and T
      and B cell numbers fell a little in old and very old subjects. Within the T cell
      compartment, helper/inducer CD4+ T cells, together with their subsets identified
      as 'naive' (CD4+/CD45RA+) and 'memory' (CD4+/CD45RO+) cells, also showed a
      decline with increased age. The suppressor/cytotoxic CD8+ subset showed no age
      related change. The levels of the cytokine interleukin 2 were very low in
      octogenarian and nonagenarian subjects, while the soluble interleukin 2 receptor
      levels increased with increasing age. The interleukin 2 levels were associated
      with number and percentage of the 'memory' (CD4+/CD45RO+) subset of T cells which
      mediates the host response to previously met antigens. Since the interleukin 2
      values were very low in the oldest groups and were associated with a reduced
      'memory' (CD4+/CD45RO+) compartment, this suggests a possible mechanism of why
      the very elderly subject is more susceptible to morbidity and mortality from
      infectious or other agents.

PMID- 9138977
TI  - Age-related changes in secretion and metabolic effects of a trial natriuretic
      factor in rats.
AB  - The effects of aging on the secretion of and renal sensitivity to atrial
      natriuretic factor (ANF) were studied concomitantly in both senescent (25- to 34
      month-old) and in adult (7- to 13 month-old) female and male Long-Evans rats. The
      plasma concentrations of ANF, measured in response to either a mild stimulation
      induced by a hypertonic volume expansion (i.e., 20 min after the onset of a
      continuous infusion during 15 min of a 2.5% NaCl solution; n = 18 old and 23
      adult rats) or an intense stimulation produced by morphine injection (i.e., 30
      min after an intraperitoneal injection of 5 mg morphine/100 g body weight; n = 11
      old and 12 adult rats), were significantly lower (approximately -34 and -80%,
      respectively) in old as compared with adult animals. Acute intravenous injection
      of exogenous rat ANF (0.10 and 0.40 mu g/100 g body weight) induced similar
      natriuretic, diuretic, and kaliuretic effects in aged (n = 18) and in adult (n =
      23) rats. The present data suggest that the significantly reduced (about -20%)
      natriuretic and kaliuretic responses of the aged rat, observed 20 min after the
      onset of hypertonic volume expansion, could be partly due to a primary defect in
      cardiac production and/or release of ANF rather than to a reduction of renal
      responsivity to ANF.

PMID- 9138978
TI  - Melatonin as an antiaging drug: between facts and fantasy.
AB  - This contribution makes an attempt to critically reassess the impressive career
      of melatonin from a stepchild of hormone research to a best-seller of drug
      marketing. Melatonin is an extremely interesting hormone. It is involved in the
      regulation of seasonal and circadian fluctuations of other hormones and in the
      synchronization of many different aspects of circadian rhythmicity to the light
      dark cycle. In addition to these receptor-mediated functions, melatonin may act
      as a modulator of intracellular signal transduction to enhance or suppress the
      responses of many different cells to other incoming signals. Melatonin is also a
      potent scavenger of reactive oxygen species and may thus protect cells and
      tissues against radical-mediated damage. The production of melatonin declines
      with increasing age, and circulating melatonin levels are affected by certain
      pharmacological or physiological manipulations, notably food restriction which
      increases melatonin levels and prevents its age-related decline. Animal and cell
      culture experiments suggest that melatonin may have beneficial effects on certain
      aspects of aging and age-associated diseases. Of particular interest in this
      respect are reports on the influence of melatonin on the brain and the immune
      system. More research data are urgently needed in order to more clearly define
      the possible sites and mechanisms of these actions. Clinical studies need to be
      performed in order to identify possible side effects of long-term melatonin
      treatment, especially in elderly and diseased subjects. Serious concerns are
      raised about the use of uncontrolled, impure, or partially degraded melatonin
      preparations.

PMID- 9138979
TI  - Lack of association between helicobacter pylori and gastric atrophy or intestinal
      metaplasia in elderly patients.
AB  - Helicobacter pylori (Hp) is associated with gastritis and peptic ulcers. It may
      also induce gastric atrophy (GA) and intestinal metaplasia (IM), and these
      changes may be the precursors of gastric carcinoma. The aim of this study was to
      determine if GA or IM is associated with Hp infection in elderly patients.
      Consecutive patients admitted for gastroscopy were recruited. Multiple biopsies
      were taken for histology and rapid urease (CLO) tests along with IgG enzyme
      linked immunosorbent assay antibodies and (13)C-urea breath tests. Statistical
      analysis was by chi(2) tests. 114 patients were recruited, the average age was
      78.9 + or - 5.4 years. Histology was available on 105 patients, 80 (76.2%) had
      gastritis, and 61/80 (76.25%) had evidence of definite current Hp infection.
      Seven patients had reflux gastritis, and these were excluded from the analysis
      described below. 20 patients had GA and 24 IM. The relationship between Hp and GA
      or IM was investigated by dividing patients into four groups: Group 1 patients (n
      = 57) were taken to be definitely currently infected (GA 7 patients, IM 11, both
      1). Group 2 patients (n = 18) had old infection (GA 2, IM 4, both 3). Group 3
      patients (n = 16) have never been infected previously (GA 1, IM 1, both 3). Group
      4 patients (n = 4) had a poor immunological response to Hp (GA 1, IM 1, both 0).
      There were no significant differences in the numbers of patients with GA or IM in
      any group as compared with any other, with the exception of less patients with
      histological evidence of combined GA and IM among patients with definite current
      infection as compared with those with either previous infection (p = 0.04) or
      'never' infection (p = 0.03). We conclude that the mucosal changes of GA or IM
      are not consistently associated with Hp infection in the elderly.

PMID- 9138980
TI  - [A test to evaluate the activity of n-acetyltransferase and catalase in
      pathologic states of pregnancy].
AB  - The activity of N-acetyltransferase (NAT) and catalase was measured in the
      tissues of placenta, full venous blood and full umbilical cord blood in 141
      complicated pregnancies. The control group consisted of 34 physiological
      pregnancies. The enzymes activity was marked by use of biochemical methods. It
      has been shown that NAT and catalase is the most active in the group of
      physiological pregnancies. The decrease of NAT and catalase in venous and
      umbilical cord blood is correlated with the decrease of the activity these
      enzymes in placenta.

PMID- 9138981
TI  - [Level of cortisol in blood serum of maternal and umbilical cord during various
      methods of delivery].
AB  - The effect of stress during labor on the plasma concentration of cortisol was
      studied in 82 women. The total cortisol levels in the maternal serum and cord
      blood were measured by radioimmunoassay during spontaneous labor (PSN), oxytocin
      induced labor (PI), elective cesarean section (CCE), and emergency cesarean
      section (CCC). The result indicate that cortisol level was higher after PI (710
      ng/ml) and CCC (755.4 ng/ml) and lower in CCE (278.9 ng/ml) in the maternal vein.
      In cord blood after CCC was higher (530.8 ng/ml), and lower after CCE (157.8
      ng/ml).

PMID- 9138982
TI  - [The effect of PGE2 on vascular resistance in human placentas perfused in vitro].
AB  - In vitro perfusions of the fetal part of 15 placentas were performed. An arterial
      system was singularly injected by 0.75 mg of PGE2 (Prostin-Upjohn). Persistent
      effect of a perfusion pressure increase reflecting the placenta vessels
      resistance was observed.

PMID- 9138983
TI  - [Endometriosis in postoperative abdominal wall scar after cesarean section].
AB  - Endometriosis in postoperative abdominal wall scar after cesarean section is
      rarely observed. In professional literature, only single cases are reported. The
      author presented 27 cases of this diseases. The women were treated in the
      Gynaecology and obstetrics Department of Medical School in Lodz, in 1985-1994.
      Because of the small response to pharmacological treatment, the treatment of
      choice was surgical of the lesion. In the article, the literature concerning the
      disease is presented.

PMID- 9138984
TI  - [Anatomic and radiologic studies of of ovarian arteries in women of various
      ages].
AB  - The main source of ovarian arterial blood supply is so called an ovarian arcade.
      It is an arterial system made of the uterine and ovarian artery junction. Depend
      on the source of information, there are different descriptions of ovarian arcade
      vessels, as well as there are different anatomical nomenclature. Anatomical
      material was taken from 63 women aged 15 to 85. Arterial vessels were
      appropriately prepared, filled with contrast medium and X-ray examined. An
      ovarian and uterine vessels junction into the ovarian arcade was observed in the
      all examined material. In order to be include into the arcade, an appropriate
      vessel diameter had to be stated at the level of uterine and tubal end. In
      multiparas in comparison with nulliparas, an average diameter was bigger about
      17%. Number of vessels, the arcade gives to ovarian hilus is also of variable
      quantity. There are markedly less vessels in postmenopausal women.

PMID- 9138985
TI  - [Iron deficiency as a risk factor during the perinatal period].
AB  - Iron deficiency as a risk factor in the perinatal period--the review of the
      literature. The presence of iron is necessary for the metabolic processes,
      erythropoiesis, oxygen transport and respiration, thermoregulation and humoral
      and cellular immunity. Iron deficiency decreases the amplitude of adaptation of
      the pregnant women. It might be responsible for abortion or preterm labour as
      well as disarrangement of myometrial activity during labour and puerperium.
      Congenital fetal malformations and intrauterine growth retardation might be also
      stimulated by iron deficiency.

PMID- 9138986
TI  - [Immunologic response against spermatozoa in the human genital tract].
AB  - Spermatozoa are immunogenic and may induce an immune response in reproductive
      compartments. There have been controversies concerning the effect of naturally
      existing antisperm antibodies on fertility of males and females. It is known,
      that men or women suffering from unexplained infertility have often antisperm
      antibodies in their urogenital secretions and/or serum. Systemic and local immune
      responses to sperm antigens differ between each other and they may differently
      affect the fertilisation process. Physiologically, females are protected from an
      immune response against "foreign", spermatozoal antigens. Nevertheless under
      local pathological conditions antisperm antibodies can be induced and may
      interfere with fertilisation.

PMID- 9138987
TI  - [Does a physician's apron protect against nosocomial infection?].
AB  - A view on the role of doctors coats in spreading and preventing nosocomial
      infections has been presented. Although traditionally a big attention is put on
      wearing white coats by ward staff, in many instances it's protective effect is
      overestimated, while other factors may be of importance.

PMID- 9138988
TI  - [Familial translocation t (9;16) in a patient with irregular menstrual cycles].
AB  - In this report we present a family with identified carriers of unique reciprocal
      translocation t (9; 16) (q31; q13) detected through karyotyping of the patient
      with irregularity of menstrual cycles. Genetic risk for birth of a child with
      congenital anomalies was estimated as low (0.6%). However, risk for abortion was
      high. We suggest introducing cytogenetic studies in such cases.

PMID- 9138989
TI  - [Intrauterine pregnancy complicated by coexisting ectopic pregnancy].
AB  - Authors have presented the case of coexisting 11 week intrauterine and ectopic
      pregnancies in the 25 years old woman, which had earlier been operated on the
      left ovary dermoid cyst. That operation could be regarded as an ectopic pregnancy
      risk factor, but the suspicion of an ectopic pregnancy has been suggested only by
      physical examination, and sonography and laparoscopy were most important in final
      diagnosis. Ectopic pregnancy has been removed by laparotomy according to the
      progression of the disease. The case has drawn the attention to the necessity of
      thorough diagnosis in pregnant women particularly in those ones with lower
      abdominal pain in early pregnancy and with unfavorable gynaecological and
      obstetric past, for example appendages operation such as in our case. It was also
      been emphasized, that the complex diagnosing of patients with already recognized
      ectopic pregnancy should be proceeded. Sonography, especially the one equipped
      with the endovaginal probe, plays the most important part in diagnosing. In some
      questionable cases laparoscopy, along with diagnostical significance, also makes
      the surgical treatment possible.

PMID- 9138990
TI  - [A case of cervix neck pregnancy--report on conservative treatment].
AB  - Authors presented successful conservative treatment early diagnosed cervical
      pregnancy. After this procedure abdominal hysterectomy was not necessary.

PMID- 9138991
TI  - [Hematoma of the rectus sheath as a gynecologic problem].
AB  - We report a case of 54 years old female who presented an acute onset of abdominal
      pain after physical training. Left rectus sheath haematoma may clinically mimic
      torsion of ovarian cyst. Case was treated surgically, haematoma was found,
      peritoneal cavity was also controlled.

PMID- 9138992
TI  - [Cerclage of the cervix in pregnant women with cervix incompetence in the
      Department of Obstetrics and Pathology of Pregnancy, School of Medicine in Lublin
      during the years 1982-188].
AB  - We have retrospectively analyzed 77 cases of pregnant patients with cervical
      incompetence in which we performed cervical cerclage. These cases were 0.65% of
      all deliveries. The age was 20-41 years (mean 28.5). They were in second or third
      pregnancy. 62 women delivered by vaginal way and 15 by cesarean section. Only 5
      newborn had small weight for age. We discussed our results with data from other
      authors.

PMID- 9138993
TI  - [Analysis of indications for 3528 Cesarean sections based on sixteen years of
      clinical material (177-1992)].
AB  - Analysis was subjected on 3528 cesarean sections made in I Obstetric and
      Gynecology Clinic Academy of Medicine in Bytom between 1977-1992. At the drop in
      general number of deliveries there were noticed upward tendencies in percentage
      of cesarean sections but during last two years this increase was inhibited. The
      ratio of sudden and planned indications determined by us as index of indications
      (N/P) oscillated from 0.16 to 0.31. Among sudden indications imminent
      intrauterine fetus asphyxia was noticed most often and among planned indications
      state after cesarean section and loss of progress of delivery.

PMID- 9138994
TI  - [Management of breech delivery and its influence on the newborn].
AB  - Authors analyse the newborns general well-being after the breech delivery in the
      two-years periods in 1983-84 and 1993-94. During this period of time the routine
      delivery by the caesarean section in primiparas was introduced. The statistically
      significant improvement in the general state on newborns measured by the Apgar
      score was observed in primiparas. All other data were comparatively similar.

PMID- 9138995
TI  - [Forceps delivery--obstetric indications and outcome].
AB  - Authors analysed 170 forceps delivery in comparison to the control group of
      normal vaginal delivery. We analysed mothers age, obstetrical history,
      gestational age and duration of labour as well as traumatization, loss of blood
      and hospitalisation time. Analysed concerned as well the newborns state in the
      Apgar score its delivery way and newborn injuries. The most frequent indication
      for the forceps delivery was the imminent foetal asphyxia. The second stage of
      delivery lasted significantly longer, the blood lost was greater and the
      hospitalisation prolonged. Newborns presented poorer after-delivery condition
      measured in the Apgar score.

PMID- 9138996
TI  - [Evaluation of the diagnostic usefulness for ultrasonographic and
      echocardiographic lethal markers in fetal pulmonary hypoplasia. Analysis of 11
      cases].
AB  - Results of ultrasonographic and echocardiographic studies of 11 fetuses were
      analysed retrospectively in relation to their pulmonary hypoplasia. Congenital
      malformations, quality of hydramnios and echocardiographical measurements of
      fetal chest were estimated. The best symptoms of pulmonary hypoplasia were:
      oligo/ahydramnios, absence of fetal breathing movements and malformations in
      fetal chest cavity (diaphragmatic hernia, cardiomegaly, hydrothorax). Systemic
      malformations were present in each case. The measurements such as CC, CA, HA, (CA
      HA) x 100/CA were not accurate enough and we did not find any statistical
      differences between the control and the studied group. Finding several factors
      predisposing to lung hypoplasia means that its lethal form may be present in
      fetus.

PMID- 9138997
TI  - [The value of CA 125 levels in serum, peritoneal fluid and tumor in women with
      ovarian cancer].
AB  - The patients group consisted of 133 women with primary ovarian carcinoma at the
      average age of 56. According to the size of tumor diagnosed preoperatively,
      patients were divided into 3 groups: with tumor smaller than 5 cm, with tumor
      between 5 and 10 cm and over 10 cm. 74 women were tested for antigen CA 125 in
      the serum preoperatively and all of them were tested for it postoperatively.
      Moreover 28 samples of the antigen were tested in the peritoneal fluid and 7
      samples in the tumor tissue. The tests on correlation of CA 125 level and the
      tumor size, process of cancer disease and histopathological type of cancer were
      carried out. Our data show that the reduction of tumor mass decreases marker
      level in the serum. Not in all cases of progression and recurrence the increased
      level of CA 125 was observed. There is, however, correlation between increased CA
      125 level and histopathological type of cancer--the highest for serous and
      undifferentiated cancers. The marker level is the highest in the tumor and
      decreases in the peritoneal fluid and serum which proves that the marker is
      produced by tumor cells.

PMID- 9138998
TI  - [Evaluation of the basis for elective appendectomy in gynecologic laparotomy].
AB  - The usefulness of elective appendectomy in gynecological laparotomy has been
      discussed on the basis of data from 2157 operations. A high rate of pathology has
      been found in patients without any clinical manifestations including 56.6%
      inflammatory changes and 0.51% malignant neoplasmas. Elective appendectomy does
      not influence complications rate, duration of hospitalisation, excludes the need
      for future operation and may lower the costs of health care.

PMID- 9138999
TI  - [Pros and cons of elective appendectomy in gynecologic laparotomy].
AB  - The problem of elective appendectomy still raises rational and emotional
      controversy among surgeons. Here is presented discussion and our opinion that
      strongly supports the idea of performing elective appendectomy during
      gynecological laparotomy.

PMID- 9139000
TI  - [Calcifications visible in mammographic examination as a diagnostic problem].
AB  - Mammography can detect various types of calcification in the breast. Their
      correct estimation enables detection of the breast cancer in situ. In our
      research there have been analyzed various types of calcification available on
      radiograms, which have been placed in publications. The aim was to find out which
      of them could be characteristic for cancer. Calcifications that are seen in
      mammography can be divided into: microcalcifications, macrocalcifications in
      galactophorous ducts, in blood and sympatic vessels. Pathogenesis of
      microcalcifications is not explained. There exist hypotheses which claim that
      they are caused by focuses of necrosis, changes in acid mucopolysaccharides in
      the midst of galactophorous ducts or in mitochondria. Differentiation between
      microcalcifications and macrocalcifications is based on variations in size, shape
      and radiological changes which they accompany.

PMID- 9139001
TI  - [Conjoined twins--diagnostic and therapeutic strategies].
AB  - The authors have analysed three cases of twin pregnancies complicated by the
      conjoined of the fetuses. Based on own experience and informations from the
      literature the general diagnostic and therapeutic strategy of dealing with this
      condition has been purposed.

PMID- 9139002
TI  - [Abdominal desmoid in a 28-year old pregnant woman].
AB  - Desmoid tumors of abdomen were described based on the literature. The unusual
      case of 28 years old pregnant women with tumor infiltrated symphysis was
      analyzed. The diagnostic procedures, surgical technique using the artificial
      material as well as the delivery was shown.

PMID- 9139003
TI  - [The effect of uropolinum on phagocytosis of sperm by cultured peritoneal
      macrophages in rats].
AB  - Peritoneal macrophages and sperm were cultured with and without uropolinum. The
      macrophages were isolated from female rat peritoneal cavities and sperm from male
      rat cauda epididymis. Sperm phagocytosis index was estimated in cultures with
      increasing concentrations of uropolinum. Authors concluded that uropolinum
      inhibited sperm phagocytosis by peritoneal macrophages. The results were verified
      by electron microscopic examinations. The latter additionally revealed that
      uropolinum enhanced an adhesion between the macrophages.

PMID- 9139004
TI  - [Non-obstetric indications for cesarean section from five years of material].
AB  - During the period 1990-94, in the Institute of Obstetrics and Gynecology. The
      Medical Academy of Gdansk 13,079 deliveries took place including 1635 cesarean
      section, which makes 12.5%. In 282 women (17 percent of these) surgical
      procedures were performed due to a non-obstetrical indications, 122 pregnancies
      were complicated by maternal diabetes mellitus-these women were excluded from the
      present study. A constant percentage increase of cesarean sections was observed
      by 1.45% every year, from 10.23% to 15.97%, but the percentage of non-obstetrical
      indications for operative delivery was stabilized to approximately 9.79%. The
      most frequent non-obstetrical indications for the cesarean section were
      pregnancies complicated by: hypertension-33.75%, ophtalmological-20.57%, uterine
      myomas-16%, women heart diseases-10%, pelvic pathology-8.75%, neurological
      disorders-8.12%. The indications for cesarean section did not have influence on
      gestational age.

PMID- 9139005
TI  - [Pregnancy induced changes in lipid-lipoprotein serum profile in women and
      newborn birth weight].
AB  - The pregnancy is associated with hyperlipoproteinemia including an increased
      level of total cholesterol, LDL-cholesterol, HDL2 and HDL3-cholesterol and
      triglycerides. The mechanism of pregnancy associated hyperlipoproteinemia remain
      unclear. The aim of the study was to estimate the relationship between the
      newborn body mass at delivery and changed by pregnancy lipid-lipoprotein blood
      profile in women. Studies were carried out in the cases of 67 women. Blood
      samples were studied at 25 week of pregnancy, during the labor, and at 5th day
      after delivery. No influence of the pregnancy-changed lipid-lipoprotein pattern
      of the mothers on the body mass of newborns was found in any of the investigated
      period.

PMID- 9139006
TI  - [The type of material primary hyperlipoproteinemia and newborn birth weight].
AB  - Twenty four cases of hyperlipoproteinemia were reported in the investigated group
      of 67 mother, which delivered behind 38 and 41 week of pregnancy newborns above
      2500 g body mass. They were characterized as IIa and IV types according to the
      WHO classification. Fifteen mothers had HLP of IV type. The average delivery body
      mass of newborns of these mothers was 3550 g. Nine mothers had HLP of IIa type
      and these mothers delivered the lightest newborns, average delivery body mass was
      3117 g while the average of with normolipidemia mothers was 3238 g. The chi 2
      test indicated that the delivery body mass of the newborns is related to the type
      of hyperlipoproteinemia of mother (p < 0.05).

PMID- 9139007
TI  - [Lipid-lipoprotein serum profile of the newborn and its birth weight].
AB  - The sixty-seven newborns were investigated. The umbilical cord blood samples were
      used to determine following indices: total cholesterol, LDL, HDL2, HDL3
      cholesterol, total phospholipids, LDL, HDL-phospholipids, triglycerides and
      apolipoprotein B. The chi 2 test indicated correlations between increased levels
      of triglycerides, phospholipids LDL and cholesterol HDL2 and decreased level of
      cholesterol LDL in the group of newborns with the lowest delivery body mass.

PMID- 9139008
TI  - [Arrhythmias and conduction block in the newborns of mothers who had received
      long-term tocolytic therapy].
AB  - Serial electrocardiograms (ECGs) were studied prospectively in 48 newborns
      exposed in utero to prolonged tokolytic therapy to beta-sympathomimetics and in
      30 newborns non-exposed in utero to beta-mimetics. Duration of exposure to
      tocolysis was at least 7 days, mean 51 +/- 36 days. The ECGs were made in 1-st
      and 3-rd day of life. The ECGs were estimated for duration the QT interval (as
      corrected QT-QTc) Cardiac event in 16 newborns from treated group and in 16
      newborns from control group were examined in 1-st day of life on a Holter
      monitor. It was found that, the prolongation of QTc time, the ventricular
      extrasystole and the atrioventricular blocks second degree (Wenckenbach's period)
      were occurred more often in the newborns whose mother had taken beta-mimetic
      drugs then in the control group.

PMID- 9139009
TI  - [Studies of human papillomavirus infection (HPV) and expression of oncoprotein p
      21 in cervix neoplasms].
AB  - Frequencies of HPV type 16 and 18, evaluated by in situ hybridization technique
      in uterine cervix carcinomas of the IIIrd stage of clinical advancement, were 54%
      and 36.5% respectively. Presence of p 21 protein was detected in 85.3% cases of
      the cancers and showed no relation to HPV infection.

PMID- 9139010
TI  - [Activity of endogenous anticoagulants (antithrombin III, protein C and protein
      S) in women after menopause treated with hormone replacement therapy (transdermal
      17 beta-OH estradiol and oral medroxyprogesterone acetate)].
AB  - The influence of hormone replacement therapy (HRT) on coagulation system has not
      been completely explained yet. We measured plasma activities of antithrombin III,
      protein C and protein S before and after 6 and 12 months of HRT in 48
      postmenopausal women. HRT consisted of transdermal estradiol and orally
      medroxyprogesterone acetate. We observed no statistically significant differences
      in plasma levels of the above endogenous anticoagulants before and during
      treatment.

PMID- 9139011
TI  - [Comparison of ultrasonographic results of the breast with progesterone levels in
      women with fibrocystic mastopathy].
AB  - Measuring the level of progesterone in 80 women who according to the ultrasound
      images had fibrocystic mastopathy. I've concluded by comparing the ultrasound
      images with the measurement of hormones that there was conformity of 75%.

PMID- 9139012
TI  - [Toxic effects of fluorine compounds on the the fetus and their effect on the
      course of pregnancy].
AB  - The effect of transfer fluorine compounds through placenta is a possibility their
      influence on fetus. There are known many examples of unprofitable activity
      fluorine compounds during pregnancy. There is mentioned among others increase
      percentage of preterm labours, stillbirths, congenital abnormalities and also
      deaths of newborns just after delivery. The mechanisms of toxic influence
      fluorine compounds on fetus have probably character of direct influence on
      embryo's cells or disturb the punction of placental tissue with following
      consequences. The real teratogenic fluorine compounds activity was not completely
      proved.

PMID- 9139013
TI  - [Undiagnosed abdominal pregnancy resulting in fetal death and surgical removal of
      the fetus].
AB  - The paper discussed problems encountered in diagnosing an abdominal pregnancy
      involving fundal and left adnexal insertion of the placenta. This rare placenta
      localisation was associated with difficulties in differing limits of the uterus
      from the oocyst in ultrasound imaging.

PMID- 9139014
TI  - [Report of the commission for the prophylaxis of anterior segment eye infections
      newborns].

PMID- 9139015
TI  - Osteopathic manifesto. III. The beginning or the end. 1981.

PMID- 9139016
TI  - [Hydrotherapy in thermal facilities in Belgium].

PMID- 9139017
TI  - [Carpal tunnel syndrome following Pouteau's fracture].

PMID- 9139018
TI  - [Interpretation of the cardiovascular effects of a 38-degrees C. bath].

PMID- 9139019
TI  - [The effect of cold on the afferent sensory conduction of the hand].

PMID- 9139020
TI  - [Evaluation methods for respiratory muscle function and their application in
      respiratory rehabilitation].

PMID- 9139021
TI  - [Neuropathies due to perhexiline maleate and their electromyographic diagnosis].

PMID- 9139022
TI  - [Clinical aspects of spasticity in adults].

PMID- 9139023
TI  - [The pharmacology of spasticity].

PMID- 9139024
TI  - [Orthopedic surgery in the child with cerebral motor disorders].

PMID- 9139026
TI  - [Bobath treatment].

PMID- 9139025
TI  - [Role of neurosurgical techniques in the treatment of spasticity].

PMID- 9139027
TI  - [Spasticity--treatment in children].

PMID- 9139028
TI  - [Treatment of spasticity in adults].

PMID- 9139029
TI  - [The physiology of spasticity].

PMID- 9139030
TI  - [Physiopathology of spasticity].

PMID- 9139031
TI  - [The role of acupuncture in physical medicine].

PMID- 9139032
TI  - [Acupuncture].

PMID- 9139033
TI  - [The history of acupuncture, Kemperaria (Hari = needle; Chiryo: treatment)
      Kemper, Doctor in Medicine, 1651-1717 (Longo. County of Lippe, Westphalia)].

PMID- 9139034
TI  - [Neurophysiology of pain. Current aspects].

PMID- 9139035
TI  - [Electroacupuncture in the treatment of pain using peripheral
      electrostimulation].

PMID- 9139036
TI  - [Electrotherapy of pain].

PMID- 9139037
TI  - [Aspects of various forms of current in electric stimulation].

PMID- 9139038
TI  - [Striated skeletal muscles. Various data on excitation-contraction coupling, bio
      energetics and various types of fibers].

PMID- 9139039
TI  - [EMG biofeedback. Various clinical applications].

PMID- 9139040
TI  - [Biofeedback of back coupling. Theory and practice in the hemiplegic patient].

PMID- 9139041
TI  - [Back pain in ossification of the ligamentum flavum].

PMID- 9139042
TI  - Structure and mechanism of phosphoenolpyruvate carboxykinase.

PMID- 9139044
TI  - Assisted reproductive technology and embryo preservation.

PMID- 9139043
TI  - Control of activity through oxidative modification at the conserved residue Cys66
      of aryl sulfotransferase IV.
AB  - Oxidation at Cys66 of rat liver aryl suflotransferase IV alters the enzyme's
      catalytic activity, pH optima and substrate specificity. Although this is a
      cytosolic detoxification enzyme, the pH optimum for the standard assay substrate
      4-nitrophenol is at pH 5.5; upon oxidation, the optimum changes to the
      physiological pH range. The principal effect of the change in pH optimum is
      activation, which is manifest by an increase in K'cat without any major influence
      on substrate binding. In contrast, with tyrosine methyl ester as a substrate, the
      enzyme's optimum activity occurs at pH 8.0; upon oxidation, it ceases to be a
      substrate at any pH. The presence of Cys66 was essential for activation to occur,
      thereby providing a putative reason underlying the conserved nature of this
      cysteine throughout the phenol sulfotransferase family. Mapping of disulfides by
      mass spectrometry showed the critical event to be the oxidation of Cys66 to form
      a disulfide with either Cys232 or glutathione, either one is effective. These
      results point to a mechanism for regulating the activity of a key enzyme in
      xenobiotic detoxication during cellular oxidative stress.

PMID- 9139045
TI  - Indirect enzyme-linked method for determining biotin in human serum.
AB  - An indirect enzyme-linked assay was developed for quantifying biotin
      concentrations in human sera. Biotin standard solutions or unknown samples are
      preincubated with streptavidin-conjugated horseradish peroxidase (streptavidin
      HRP) and added to plates coated with biotinylated bovine IgG (B-IgGb). The
      concentration of the streptavidin-HRP is such that the streptavidin binding sites
      are sufficient to bind apparently all the biotin present in samples, whereas, the
      remaining sites are inversely proportional to the amount of biotin in analysed
      sample. These sites could subsequently interact with the immobilized B-IgGb
      providing signal. The assay demonstrated dynamic range 5 to 640 ng/L, detection
      limit 2 ng/L, intra- and interassay C.V., 1.6-3.9% and 3.7-7.2% respectively,
      recovery 100-114% and linear recovery 90-117%. Serum biotin determined: healthy
      individuals 66 to 600 ng/L, pregnant women (> or = 36 weeks) 60 to 360 ng/L, and
      patients under chronic haemodialysis 0.56 to 1.62 micrograms/L. The method
      described is among those few which have been experimentally evaluated for their
      capabilitity of assessing biotin in human sera.

PMID- 9139046
TI  - A procedure for the detection of free thiol-containing proteins on a
      polyvinylidene difluoride membrane.
AB  - Bovine serum albumin (BSA), which has a free thiol, was blotted onto a
      polyvinylidene difluoride membrane. The membrane was reacted with a sulfhydryl
      reactive (maleimide-containing) biotin derivative, 1-biotinamido-4-[4'
      (maleimidomethyl) cyclohexanecarboxamido] butane (Biotin-BMCC), and then probed.
      BSA on membranes was detected semi-quantitatively at 50 ng of protein (0.76 pmol
      of free thiol) and among range of higher extent. BSA on membranes was less
      efficiently biotinylated compared with biotinylation in solution. Regardless,
      these results suggested that sulfhydryl-containing proteins were specifically and
      semi-quantitatively identified by membrane biotinylation with Biotin-BMCC.

PMID- 9139047
TI  - A descriptive model for the kinetics of a homogeneous fluorometric immunoassay.
AB  - A descriptive mathematical model was chosen to fit the antigen-antibody
      association kinetics of a new homogeneous immunometric assay for prolactin,
      involving time-resolved fluorescence detection (TRACE technology, Time Resolved
      Amplified Cryptate Emission). We paid special attention to the methodology and
      criteria applied, to yield a convenient and statistically valid model, designed
      to allow potential exploitation of kinetic information in the data processing of
      the assay. We compared specific parameterizations of an hyperbolic model, the
      Gompertz, and the monomolecular models on the basis of morphological
      considerations, a statistical analysis of fit, and an assessment of the
      parameters estimation quality, over a wide range of antigen concentrations. The
      monomolecular model gave the best fit, and the most precise and stable estimation
      of its parameters. The study of parameter properties confirmed this choice.

PMID- 9139048
TI  - An immunoligand assay for quantitation of process specific Escherichia coli host
      cell contaminant proteins in a recombinant bovine somatotropin.
AB  - We have developed a Threshold System immunoligand assay for the quantitation of
      residual, process-specific, Escherichia coli host cell contaminant proteins (HCP)
      in somavubove (a normal sequence recombinant bovine somatotropin). The assay has
      a dynamic range of 2 to 160 ng/mL, with a limit of quantitation of 2 ng/mL. Daily
      analytical precision (CV) for six replicates of the designated somavubove
      laboratory standard is 3.0%. Cumulative analytical precision for multiple assay
      runs of this standard (a total of 69 laboratory standard replicates) is 8.4%. A
      conservative alert limit of 100 ng/mL has been assigned in order to assure
      analytical precision for each assay sample under conditions of stoichiometric
      antibody excess. Although the assay was designed for use as a profile-release
      specification assay, it has also been used to validate removal of HCP by the
      proprietary somavubove purification process. This use is consistent with
      regulatory guidelines related to "well characterized" recombinant
      biopharmaceutical proteins.

PMID- 9139049
TI  - Interaction between antibodies and hapten-protein conjugates of different
      composition: theoretical predictions and experimental data.
AB  - Mathematical models of competitive ELISAs with labelled antibody and with
      labelled antigen taking into account bivalent interactions between antibodies and
      hapten-protein conjugates were developed and analyzed. It was shown that in the
      kinetic model of the immunochemical reaction the conjugate composition influenced
      the amplitude of detected signal but not ELISA sensitivity. In the equilibrium
      model decreased sensitivity correlated with bivalent complexes formation. The
      predictions were tested experimentally using 2,4-dichlorophenoxyacetic acid (2,4
      D) and testosterone as haptens. It was confirmed that increasing of the hapten :
      protein ratio resulted in formation of bivalent complexes with antibodies. The
      equilibrium binding constants for these complexes were two orders of magnitude
      higher than for monovalent ones. Optimal conjugate compositions have been chosen
      for ELISA of these haptens.

PMID- 9139050
TI  - Microparticle-enhanced nephelometric immunoassay of alpha-lactalbumin in human
      milk.
AB  - A microparticle-enhanced nephelometric immunoassay was developed for alpha
      lactalbumin quantitation in human milk. It is based on the nephelometric
      measurement of the light scattered during the competitive immunoagglutination of
      a microparticle-alpha-lactalbumin conjugate with an anti-alpha-lactalbumin
      antiserum. This immunoassay is sensitive (detection limit in reaction mixture,
      1.5 micrograms/L) and could be performed in high dilution of milk, excluding any
      interference or sample pretreatment. It allowed the quantification of alpha
      lactalbumin on a large range of concentrations (0.5-16.9 g/L) with accuracy
      (linear recovery in dilution-overloading assay) and precision (within- and
      between-run coefficients of variation from 1 to 7%). Changes in the alpha
      lactalbumin concentration of human milk during lactation were determined in 162
      samples. The concentration and ratio of alpha-lactalbumin total protein were
      found to be significantly lower in colostrum (4.9 g/l, 27%) than in transitional
      milk (5.2 g/L, 40%), then decreased in mature milk (3.4 g/L, 31%).

PMID- 9139051
TI  - [Angina pectoris].

PMID- 9139052
TI  - [Angina pectoris: progress in diagnosis and therapy. I. Physiopathology. 1.
      Asymptomatic myocardial ischemia--etiological mechanism and clinical
      significance].

PMID- 9139053
TI  - [Angina pectoris: progress in diagnosis and treatment. I. Physiopathology. 2.
      Symptoms most likely associated with angina pectoris].

PMID- 9139054
TI  - [Angina pectoris: progress in diagnosis and treatment. I. Physiopathology. 3.
      Cardiac function of the ischemic myocardium].

PMID- 9139055
TI  - [Angina pectoris: progress in diagnosis and treatment. II. Progress in imaging
      diagnosis. 1. Key points in electrocardiographic diagnosis].

PMID- 9139056
TI  - [Angina pectoris: progress in diagnosis and treatment. II. Progress in imaging
      diagnosis. 2. The role of nuclear medicine].

PMID- 9139057
TI  - [Angina pectoris: progress in diagnosis and treatment. II. Progress in imaging
      diagnosis. 3. Usefulness of echocardiography].

PMID- 9139058
TI  - [Angina pectoris: progress in diagnosis and treatment. II. Progress in imaging
      diagnosis. 4. Current status of intravascular ultrasonography].

PMID- 9139059
TI  - [Angina pectoris: progress in diagnosis and treatment. II. Progress in imaging
      diagnosis. 5. Angioscopic examination].

PMID- 9139060
TI  - [Angina pectoris: progress in diagnosis and treatment. III. Progress in
      treatment. 1. Control of risk factors of angina pectoris].

PMID- 9139061
TI  - [Angina pectoris: progress in diagnosis and treatment. III. Progress in
      treatment. 2. Therapeutic guidelines for coronary spastic angina].

PMID- 9139062
TI  - [Angina pectoris: progress in diagnosis and treatment. III. Progress in
      treatment. 3. Selection of treatment of unstable angina pectoris].

PMID- 9139063
TI  - [Angina pectoris: progress in diagnosis and treatment. III. Progress in
      treatment. 4. Practice of drug therapy of ischemic heart disease].

PMID- 9139064
TI  - [Angina pectoris: progress in diagnosis and treatment. III. Progress in
      treatment. 5. Coronary artery intervention for angina pectoris].

PMID- 9139065
TI  - [Angina pectoris: progress in diagnosis and treatment. III. Progress in
      treatment. 6. Timing for switching to surgical therapy for angina pectoris].

PMID- 9139066
TI  - [Angina pectoris: progress in diagnosis and treatment. III. Progress in
      treatment. 7. Rehabilitation of patients with ischemic heart disease].

PMID- 9139067
TI  - [Prevention of recurrence of ischemic heart disease: discussion].

PMID- 9139068
TI  - [Case of embryonal cell carcinoma treated with massive dosages of therapeutic
      agents together with transplantation of autologous peripheral stem cells].

PMID- 9139069
TI  - [Case of Emery-Dreifuss syndrome associated with atrial standstill].

PMID- 9139070
TI  - [Case of "carcinomatous cirrhosis" caused by diffuse hepatic metastasis of occult
      breast cancer].

PMID- 9139071
TI  - [Case of factor VII deficiency with systemic amyloidosis having a unique clinical
      course such as splenic rupture].

PMID- 9139072
TI  - [Case of Sweet disease with a variable clinical course].

PMID- 9139073
TI  - [Multiple-drug-resistant tubercle bacilli].

PMID- 9139074
TI  - [Large scale testing of hyperlipemia].

PMID- 9139075
TI  - Prevalence of anti-vif antibodies in HIV-1 infected individuals assessed using
      recombinant baculovirus expressed vif protein.
AB  - A 630 base pair fragment of the HIV-1 genome encompassing the entire vif open
      reading frame has been produced by the polymerase chain reaction and cloned into
      the baculovirus transfer vector pAcYM1. Extracts from insect cells infected with
      a recombinant baculovirus expressing the HIV-1 vif gene product were used in a
      radioimmunoassay to analyse 238 sera from HIV infected individuals for the
      presence of anti-vif antibodies. The overall prevalence of anti-vif antibodies in
      this group of patients was 25.3%. Stratification of the group according to CD4
      levels showed that anti-vif antibodies were more prevalent in patients with CD4
      counts below the median of the group (155 x 10(6) cells/L; P = 0.005). A
      significant increase in anti-vif antibodies was observed in patients with CD4
      levels less than 280 x 10(6) cells/L (P < 0.01) and in patients with symptomatic
      HIV infection (P = 0.0003). However, there was no significant difference in the
      prevalence of anti-vif antibodies in patients stratified according to p24 antigen
      status. The implications of these findings in the context of HIV replication are
      discussed.

PMID- 9139076
TI  - Comparison of antibody responses to different forms of HIV-1 core antigens by
      epitope mapping.
AB  - The specificity of antibodies to HIV-1 capsid (p24CA) and matrix (p17MA)
      proteins, produced in mice against unprocessed immature assembled polyprotein
      (wild-type p55 virus-like particles or chimeric p55 virus-like particles) or
      against the monomeric mature form (rp24CA/rp17MA), was analyzed by a microplate
      epitope mapping assay using a panel of synthetic peptides covering the entire
      p24CA plus p17MA sequences of HIV-1LAI. All immunized mice developed anti-p24CA
      and anti-p17MA antibodies, although the spectrum of specificity of these
      antibodies was different. Four p24 CA epitopes (residues 176-192, 201-218, 233
      253, 285-304) were recognized by anti-rp24CA/rp17MA antibodies, whereas one p17MA
      epitope (residues 11-25) and one p24CA epitope (residues 176-192) were constantly
      recognized by anti-p55 virus-like particle antibodies. These results suggest a
      different specificity pattern of anti-p24CA and anti-p17MA antibodies depending
      on whether they are produced against the soluble mature form or the immature
      assembled form of the gag proteins.

PMID- 9139077
TI  - Use of polymerase chain reaction to provide prognostic information on human
      cytomegalovirus disease after liver transplantation.
AB  - Sixty-four consecutive liver transplant patients receiving 76 organs have been
      monitored for human cytomegalovirus (HCMV) in blood and urine posttransplantation
      using a polymerase chain reaction (PCR) assay that amplifies a 149 base pair
      fragment of the glycoprotein B gene. Six hundred and twenty-six blood and 310
      urine samples were analysed during surveillance. Thirty-two patients had CMV
      infection (50%), 12 of whim progressed to HCMV disease. Detection of HCMV in
      either blood or urine was significantly associated with the presence or
      development of HCMV disease (blood, P < 0.00001; urine, P = 0.0033). All cases of
      HCMV disease were detected as PCR-positive in blood, although due to sampling
      only 50% of these patients were PCR-positive prior to disease onset. HCMV
      infection and disease were more likely in patients who suffered rejection (P <
      0.001). In addition, the median amounts of augmented prednisolone were higher in
      patients with HCMV infection and disease. In all cases, augmented prednisolone
      preceded HCMV infection/disease. There was no statistical association between CMV
      infection and death. Overall, the results show that routine use of PCR for HCMV
      in surveillance samples of blood and urine of liver transplant recipients can
      provide diagnostic and prognostic information. However, its ability to provide
      prognostic information is directly related to the availability of appropriate
      surveillance samples, emphasising the importance of the routine acquisition of
      such samples in patient management to allow preemptive anti-HCMV therapy.

PMID- 9139078
TI  - Mutated epitopes of hepatitis B surface antigen fused to the core antigen of the
      virus induce antibodies that react with the native surface antigen.
AB  - Fusion of peptide epitopes to the core antigen (HBcAg) of hepatitis B virus (HBV)
      enhances their immunogenicity, both quantitatively and qualitatively. In a number
      of vaccine-induced mutants of HBV, glycine145 of the surface antigen S
      polypeptide (HBsAg) has been replaced by arginine, resulting in loss of cross
      reactivity with antibodies to normal (wild-type) HBsAg. HBcAg fusion proteins
      carrying the immunodominant epitope of HBsAg, in which glycine145 was replaced by
      arginine, glutamic acid, or lysine, were produced in Escherichia coli and formed
      particles that displayed HBc antigenicity and immunogenicity similar to that of
      HBcAg itself. The fusion proteins also elicited T-cell proliferative
      responsiveness to HBcAg and HBsAg. Fusions carrying either wild-type or mutated
      epitopes of HBsAG showed HBs antigenicity in immunoblot analysis and antigen
      capture immunoradiometric assay, but both mutant and wild-type derivatives
      induced antibodies that cross-reacted with wild-type HBsAG. The results emphasise
      the potential for HBcAg fusion proteins in vaccines by broadening the antibody
      response in a way that could confer protection against both wild-type and variant
      form of HBV.

PMID- 9139079
TI  - Magnitude of hepatitis C virus infection in India: prevalence in healthy blood
      donors, acute and chronic liver diseases.
AB  - An enzyme immunoassay (EIA) was developed in-house for the detection of anti
      hepatitis C virus (HCV) antibody against the prevailing genotypes in India. The
      specific reactivity of the test was compared with commercial second and third
      generation EIAs and reverse transcription nested polymerase chain reaction (RT
      nested PCR). Fifteen thousand nine hundred twenty-two healthy blood donors at the
      All India Institute of Medical Sciences (AIIMS), New Delhi, India, were screened
      for anti-HCV antibody. Two hundred ninety-five (1.85%) of these donors were
      positive. The screening was also used to determine how many patients with acute
      hepatitis and chronic liver diseases were positive for anti-HCV antibody. Five
      hundred sixty-four chronic liver disease patients were screened for anti-HCV
      antibody and 78 (13.83%) were found positive. Two hundred forty-seven sporadic
      acute viral hepatitis patients were screened for viral infection markers.
      Hepatitis B and E viruses (HBV and HEV) were the major etiologic agents. HCV was
      associated with 9% of the acute cases. Anti-HCV core IgM with HCV RNA detection
      were found to be helpful for the diagnosis of acute HCV infection.

PMID- 9139080
TI  - Infection with GB virus C in patients with chronic liver disease.
AB  - Infection with putative non-A to E hepatitis virus, designated GB virus C (GBV
      C), was surveyed in 286 patients with chronic liver disease in Japan. RNA of GBV
      C was detected, by reverse-transcription polymerase chain reaction with nested
      primers from the 5'-noncoding region, in 19 patients (6.6%) at a frequency higher
      (P < 0.001) than in three of 275 (1.1%) normal controls. It was detected in three
      of 83 (4%) patients with hepatitis B virus infection, 15 of 188 (8%) patients
      with hepatitis C virus infection, and one of 12 (8%) patients without evidence of
      ongoing infection with hepatitis B or C virus. GBV-C RNA was detected in nine of
      186 (5%) patients with chronic hepatitis aged 51.2 +/- 13.3 years, six of 64 (9%)
      with liver cirrhosis aged 62.9 +/- 11.4 years, and four of 36 (11%) with
      hepatocellular carcinoma aged 62.0 +/- 11.1 years. Nucleotide sequences of 100
      base pairs in the helicase region of GBV-C isolates from the 19 patients varied
      up to 21%, while sequences of 33 deduced amino acids were conserved and differed
      only by up to 6%. These results indicate that infection with GBV-C in patients
      with non-B, non-C chronic liver disease would not be frequent, although the
      sensitivity of the detection method could be improved. Coinfection of GBV-C with
      hepatitis B or C virus, as well as the duration of infection, might accelerate
      the progression of chronic liver disease.

PMID- 9139081
TI  - Detection of adenovirus DNA in peripheral blood mononuclear cells by polymerase
      chain reaction assay.
AB  - Adenovirus can establish persistent infections which may reactivate and cause
      disease in immunocompromised hosts. Lymphocytes have been postulated to serve as
      a site of adenoviral persistence based upon the ability to isolate adenovirus
      from tonsils and to detect adenovirus DNA by Southern blot hybridization in
      peripheral blood mononuclear cells (PBMC). To test this hypothesis, a more
      sensitive and specific polymerase chain reaction (PCR) assay was developed to
      detect adenovirus DNA. Two sets of nested primers were designed to conserved
      sequences in the adenovirus E1A and hexon genes. The E1A and hexon primers
      amplified DNA from representative adenoviral serotypes in all six adenoviral
      groups (A-F). Both primers detected a single copy of the adenovirus type 2 genome
      but were less sensitive for the group B type 35. None of 33 PBMC specimens from
      healthy adults and only one of 40 pediatric samples was positive (at a low level)
      for adenovirus DNA by nested PCR assay. In comparison, PBMC from two children
      with fatal adenoviral infection were both strongly positive for adenovirus DNA.
      It is concluded that, in contrast to a previous study, PBMC are not a common site
      of persistent group C adenoviral infection. In addition, assay of PBMC by the
      adenovirus-specific PCR may help detect early invasive disease and warrants
      further evaluation.

PMID- 9139082
TI  - Relative functional affinity of specific anti-core IgG in different categories of
      hepatitis B virus infection.
AB  - While resolution of hepatitis B virus (HBV) infection occurs in most cases, a
      carrier state can exist in which the HBV surface antigen (HBsAg) persists. Some
      carriers are also positive for the HBV "e" antigen (HBeAg), indicative of high
      viral replication. Others are HBV "e" antibody (anti-HBe)-positive carriers in
      whom there appears to be a fall in the level of viral replication with the
      appearance of antibodies against the "e" antigen. The former group of carrier is
      considered to be at a higher risk of transmitting HBV infection than the latter.
      In order that a carrier state may occur, some degree of tolerance to the
      infectious agent must exist. A study of the rate of increase of specific antibody
      avidity following infection provides a means of assessing the maturity of the
      immune response to an infectious agent. Since antibodies specific for the HBV
      core antigen (HBcAg) are produced in almost all cases of HBV infection and the
      HBeAg and HBcAg share a large number of amino acids and some B- and T-cell
      epitopes, the increase in the avidity of antibodies against the HBV core antigen
      (anti-HBc) in cases of acute, resolving HBV infection and in HBV carriers has,
      therefore, been studied. An increase in the avidity of specific antibody, similar
      to that seen in other viral infections, was observed following acute, resolving
      infection. However, low avidity antibody persisted longer in carriers who
      remained positive for HBeAg, whereas in cases where there were antibodies
      specific for HBeAg, the anti-HBc antibody was of high avidity. Analysis of
      sequential sera from carriers who seroconverted from HBeAg-positive to anti-HBe
      positive showed that an increase in anti-core avidity could predate
      seroconversion from HBeAg-positive to anti-HBe-positive status. Thus, anti-HBc
      avidity studies may be of diagnostic and prognostic significance.

PMID- 9139083
TI  - Rapid detection and serotyping of adenovirus by direct immunofluorescence.
AB  - Four fluorescent antibody reagents were evaluated for their suitability for the
      identification of adenovirus isolates by immunofluorescence. The antibodies used
      in the reagents consist of monoclonal antibodies against adenovirus type 3 (Ad3),
      Ad4, Ad8, and adenoviruses of subgroup C (Ad1,2,5,6), serotypes known to occur in
      outbreaks of disease. Most of the monoclonal antibodies employed were reactive
      against type-specific antigens found on the hexon protein. Reagents employing two
      noncompeting anti-hexon antibodies were more sensitive than reagents prepared
      with only one monoclonal antibody, although both types of reagents exhibited a
      high degree of specificity. Five hundred and seventeen adenovirus isolates (359
      of which had previously been typed by other methods) and 46 nonadenovirus
      isolates were examined with all four type-specific reagents in parallel with an
      adenovirus group-specific reagent. The results indicate that direct typing of
      adenovirus isolates is feasible, leading to significant savings in time compared
      to other typing methods and should contribute to the management of certain
      adenovirus infections, particularly during outbreaks.

PMID- 9139084
TI  - Virologic, immunologic, and clinical follow-up of a couple infected by the human
      immunodeficiency virus type one, group O.
AB  - The pathogenic course (virologic, immunologic, and clinical changes) of infection
      due to human immunodeficiency virus type one (HIV-1) group O viruses is unknown
      at present. To address this issue, serial HIV-1 isolates from a married couple
      (patients A and B) infected with a group O virus were analyzed to determine the
      temporal association between disease status and alterations in several parameters
      including plasma viral burden as measured by semiquantitative polymerase chain
      reaction, changes in CD4+ T cells, presence of neutralizing antibodies, and the
      ability to induce syncytia on the MT2 cells. For patient A who has been
      asymptomatic for at least 8 years, both the absence of syncytium-inducing (SI)
      variants and the presence of autologous and heterologous neutralizing antibodies
      correlated with a clinically healthier status. In contrast, a switch from NSI to
      SI variants was observed in patient B in 1990, followed by an expanded in vitro
      host range, increased viral burden, and a sharp decrease in CD4+ T cells 4 years
      later. Moreover, plasma obtained from this patient uniformly failed to neutralize
      both autologous and heterologous viruses. These observations in patient B
      correlated with a slightly unfavorable clinical status. Based on our preliminary
      results, it appears that the pathogenic course of infections due to group O
      viruses is similar to that reported previously for infections due to group M
      viruses.

PMID- 9139085
TI  - High interferon alpha levels in placenta, maternal, and cord blood suggest a
      protective effect against intrauterine herpes simplex virus infection.
AB  - Interferons (IFN) are produced by the placenta during pregnancy, and they can be
      detected in the maternal and fetal blood. Although the antiviral potential of
      IFNs is well established, it remains unclear whether the IFNs associated with
      pregnancy can prevent transplacental spread of viral infection. The present study
      was undertaken in order to determine the possible protective effect of
      placentally produced IFN-alpha on fetal acquisition of herpes simplex virus
      (HSV). Nine mothers with a known history of genital HSV infection were studied.
      In five cases IFN-alpha was detected in the placenta, maternal, and fetal blood,
      whereas in three cases IFN-alpha could not be detected. in the remaining case,
      IFN-alpha was found only in the maternal blood. As corroborated by the
      serological evidence of early HSV infection in the cord blood, the single case of
      vertical HSV transmission was observed in the group of IFN nonproducers.
      Furthermore, virus transmission did not occur in cases where IFN-alpha was
      present in the placenta and simultaneously in the maternal and fetal
      circulations. Thus, the present data indicate that high levels of IFN during
      pregnancy may protect the fetus from acquiring a possibly fatal intrauterine HSV
      infection.

PMID- 9139086
TI  - Detection of latent varicella-zoster virus infection in human vestibular and
      spiral ganglia.
AB  - Varicella-zoster virus (VZV) becomes latent in the sensory ganglia after primary
      infection and VZV DNA has been found in human trigeminal, thoracic, and
      geniculate ganglia. In this study, human vestibular and spiral ganglia, which do
      not received innervation from the skin, were examined for VZV DNA using the
      polymerase chain reaction. VZV DNA was detected in 2 of 10 (20%) vestibular
      ganglia and in 2 of 10 (20%) spiral ganglia from five adults. VZV DNA was
      undetectable in either type of ganglion from a newborn and from two of the five
      adults. These two adults were VZV seronegative. The results indicate that VZV
      becomes latent in several types of sensory ganglion after primary infection and
      suggest the possibility that reactivation of the virus from the vestibular and
      spiral ganglia may cause disorders in the labyrinth.

PMID- 9139087
TI  - Hepatitis C virus: quantitation and distribution in liver.
AB  - The optimal method for viral quantitation and the most appropriate site for
      determining viral load in patients with chronic hepatitis C virus (HCV) infection
      are unknown. We developed a method for measuring HCV RNA in the liver with the
      following features: 1) efficient extraction of RNA from tissue (89% of RNA
      recovered); 2) accurate amplification using branched DNA with strong concordance
      between a single sample tested on multiple occasions either in the same or in
      different runs; 3) good sensitivity (95%) and specificity (100%). HCV RNA was
      detected in as little as 2 mg of tissue, and viral load determined in a needle
      biopsy was representative of viral load in other parts of the liver. Within
      individual livers, 68% of the samples quantitated were within 1.5-fold of the
      geometric mean, and 95% were within 2.2-fold of the geometric mean. The mean
      ratio of virus in the liver and serum was 103, range 17.4-286. A delay of 30
      minutes before freezing the liver tissue resulted in a reduction in the measured
      viral load in some, but not all instances. A sensitive, specific and reproducible
      method for quantitating HCV RNA in the liver has been developed. Measurement of
      viral load at one site was representative of viral load at other sites. While
      hepatic HCV RNA levels are consistently greater than serum levels, the ratio of
      liver of serum viral load varies widely. The clinical use of measurement of viral
      load in the liver remains to be defined.

PMID- 9139088
TI  - Analysis of mother-to-infant transmission of hepatitis C virus: quasispecies
      nature and buoyant densities of maternal virus populations.
AB  - Mother-to-infant transmission of hepatitis C virus (HCV) was analyzed by
      sequencing of viral RNA and semiquantitative polymerase chain reaction following
      ultracentrifugation of maternal sera. In two mother-infant pairs, the
      hypervariable region 1 (HVR1) and carboxyl terminus of envelope 1 (E1) were
      sequenced. Both viral sequences in the infants were less diverse than those of
      their mothers. Although the E1 sequences were almost identical in each mother
      infant pair, the HVR1 sequences of the infants were related, but not identical,
      to those of the mothers. Serial examinations of one infant revealed that the HVR1
      nucleotide sequence did not change from 10 days to 3 months of age. In six
      mothers with uninfected infants, all of the dense fractions of sera contained
      significant amounts of HCV RNA, whereas in six mothers with infected infants,
      only two of those fractions contained significant amounts of HCV RNA. These
      results indicate that the strains of HCV detected in the infants were not
      dominant in the mothers, but were still transmissible to the infants. As dense
      fractions are known to contain antibody-bound HCV particles, maternal antibodies
      against HCV may inhibit viral transmission.

PMID- 9139089
TI  - Detection and genotyping of the hepatitis C RNA in tear fluid from patients with
      chronic hepatitis C.
AB  - Tear fluid from 51 patients with chronic hepatitis C virus (HCV) infection was
      analyzed for the presence of the hepatitis C RNA to assess the potential role of
      this fluid in virus transmission. HCV sequences were amplified from sera and tear
      fluids by nested polymerase chain reaction using primers from the 5' non coding
      region of the virus genome. Positive samples were genotyped by the LiPA
      procedures. HCV RNA was detected in 76.5% (39/51) of the sera and in 9.8% (5/51%)
      of the tear fluid samples. The presence of the RNA in the tear fluid was
      independent of the severity of the hepatitis and of the viral load as measured by
      the branched DNA assay. The genotypes of the tears and serum isolates were
      different for two patients. For another patient, the HCV RNA was positive in the
      tear sample but negative in the serum sample. These findings suggest that tear
      fluid may transmit HCV but the source of HCV RNA in this fluid needs to be better
      understood.

PMID- 9139090
TI  - Analysis of influenza A H3N2 strains isolated in England during 1995-1996 using
      polymerase chain reaction restriction.
AB  - A polymerase chain reaction-restriction (PCR-restriction) endonuclease assay was
      developed to allow rapid analysis of influenza A H3N2 viruses circulating in
      England during 1995-1996. Restriction endonuclease digestion with two enzymes of
      amplicons derived from PCR of the HA1 portion of the influenza haemagglutinin
      (HA) gene was able to differentiate antigenically similar influenza strains into
      two groups. Group I variants were similar genetically to the 1995/96 vaccine
      strain, A/Johannesburg/33/94, whereas the HA sequences of Group II variants were
      similar genetically to the reference virus A/Thessaloniki/1/95. Of the 700
      England A H3N2 strains isolated between February 1995 and the end of April 1996,
      384 were analysed by this method. PCR-restriction analysis of sequential
      influenza isolates revealed a temporal alteration in prevalence of two variants.
      Groups I and II variants cocirculated with equal frequency during a period of
      sporadic influenza activity, but following the onset of epidemic influenza
      activity in 1995, only Group II variants were detected. PCR- restriction analysis
      was found to be a rapid method for studying genetic variation which could be
      applied to a large number of samples and provide information about the direction
      of genetic drift in the HA gene of influenza virus.

PMID- 9139091
TI  - Avidity determination of IgG directed against tick-borne encephalitis virus
      improves detection of current infections.
AB  - Recently, avidity determination of IgG has been introduced successfully into
      virus serology as an additional and specific means for confirmation or exclusion
      of current infections. This simple and highly reproducible method can compensate
      for problems arising by classical serology, which include lack of detectable IgM
      responses during primary infections and persistent IgM responses after past
      infections. We show that avidity determination can be applied successfully for
      serological diagnosis of TBEV infection. Using the urea denaturation method,
      primary TBEV infections showed anti-TBEV IgG of low avidity (avidity index <
      0.4), whereas sera from individuals with past infections exhibited high avidity
      IgG. The retrospective analysis of cases with clinical symptoms of TBEV infection
      in the absence of detectable anti-TBEV IgM showed that a significant number of
      these cases (5/45) had anti-TBEV IgG of low avidity, indicating current
      infection. We recommended the use of avidity determination as a method for
      routine TBEV serology.

PMID- 9139092
TI  - Adenovirus-receptor interaction with human lymphocytes.
AB  - Lymphocytes play a key role in cell-mediated immunity and are host cells for
      several viral and bacterial pathogens. Their importance in adenovirus (Ad)
      infections is not yet fully understood. The initial event, the attachment of Ad
      to lymphocytes and their subsets, was examined using flow cytometry. The study
      included analysis of stimulated T cells in binding assays with FITC-labeled Ad
      fiber. The results confirm that native peripheral lymphocytes express very small
      amounts of Ad receptors. Stimulation with PHA and interleukin 2 induced the
      expression. The presence of Ad DNA as a sign of internalization in stimulated
      cells was demonstrated using the polymerase chain reaction. The findings suggest
      that lymphocytes after stimulation can turn into target cells for Ad. This is
      particularly important if there are indications for persistence of Ad, and in the
      case of immunocompromised patients severe, life-threatening diseases can develop.

PMID- 9139094
TI  - Short-course indomethacin prevents heterotopic ossification in a high-risk
      population following total hip arthroplasty.
AB  - The efficacy of a 10-day course of indomethacin in preventing heterotopic
      ossification after total hip arthroplasty was studied in a consecutive series of
      male patients who were at increased risk for bone formation. Between September
      1991 and June 1994, all male patients (123 hips in 109 patients) who underwent
      total hip, revision, or surface arthroplasty were placed on a 10-day course of
      indomethacin. Of these, 106 patients (119 hips) successfully completed the 10-day
      course. There was no significant formation of heterotopic ossification (Brooker
      grade III or IV). From a group of 45 known heterotopic bone formers following
      previous total hip arthroplasty, only 2 developed new heterotopic ossification.
      Overall there were 9 (7.6%) new cases of heterotopic ossification: 7 Brooker
      grade I (5 primary and 2 revision cases) and 2 Brooker grade II (both primary
      cases). A 10-day course of indomethacin prevents the more significant grades of
      heterotopic ossification and is effective at reducing the incidence of
      heterotopic ossification following total hip arthroplasty. Further, this regimen
      appears safe and cost effective.

PMID- 9139093
TI  - Wear of retrieved cemented polyethylene acetabula with alumina femoral heads.
AB  - Four yttrium-stabilized alumina ceramic-on-polyethylene articulations obtained
      from patients who were undergoing revision surgery for sepsis (3) or recurrent
      dislocation (I) between 34 and 73 months were evaluated to assess their in vivo
      wear performance. The annual volumetric wear of the acetabular components
      determined directly by a fluid displacement method ranged from 58 to 140 mm3/y.
      Scanning electron microscope examination of these four ceramic heads revealed
      similar surface damage in all cases from a variety of causes. These included
      differential granular wear (alumina grains and yttrium-stabilized alumina grains
      at different depths), multidirectional scratches with heaped up boundaries, and
      incompletely sintered grains, as well as the formation of craters and separation
      of grain boundaries. The femoral heads in this small series of revision cases
      show that yttrium-stabilized alumina ceramic heads may develop surface
      irregularities from either manufacturing processes or in vivo use. The wear rates
      of this type of alumina-on-polyethylene articulation up to the time of revision
      were not substantially different from those found in other metal-on-polyethylene
      articulations retrieved at revision surgery.

PMID- 9139095
TI  - Scandinavian multicenter porous coated anatomic total hip arthroplasty study.
      Clinical and radiographic results with 7- to 10-year follow-up evaluation.
AB  - Four hundred ninety-four patients (539 hips) with a mean age of 50.1 (SD, 9.7)
      years entered a prospective, multicenter study of the Porous Coated Anatomic
      (Howmedica, Rutherford, NJ) total hip arthroplasty. The preoperative diagnoses
      were primary osteoarthrosis (297 hips), secondary osteoarthrosis to childhood
      diseases (88 hips), fracture (73 hips), inflammatory arthritis (26 hips),
      idiopathic avascular necrosis (28), and miscellaneous (27 hips). After a mean
      follow-up period of 6 years and 10 months, 71 hips had been revised. The mean
      Harris hip score increased from 43 (15.7) to 94 (7.4) at the last follow-up
      evaluation, without any deterioration with time. After 7 years, the combined
      survival rate for the cup and/or stem using revision as endpoint was 92.2%.
      Radiographic failure, defined as migration of either component more than 5 min
      and/or focal osteolysis, was registered in 72 stems and 96 cups. The combined
      clinical (revision) and radiographic 7-year survival rates were 61.1 (+/-5.2) and
      59.7 (+/-5.3) for the stem and cup, respectively. Statistical analysis revealed
      that young age and poor fill rate influenced the rate of stem failure, whereas
      cup failure was difficult to predict. Four variables were associated with stem
      subsidence: loosening of beads, pedestal formation, sclerotic lines in Gruen zone
      7, and acetabular granuloma. According to our findings, the 5- to 10-year
      complication rate with this implant is high. Therefore, continuous radiographic
      follow-up evaluation of these cases is strongly recommended, to enable revision
      before severe destruction of bone or catastrophic clinical failure has occurred.

PMID- 9139096
TI  - 6- to 10-year experience using countersunk metal-backed patellas.
AB  - Three hundred two consecutive cementless total knee arthroplasties (Natural Knee,
      Intermedics Orthopedics, Inc., Austin, TX) were performed using a metal-backed,
      porous-coated patellar component. Fifty-nine patients died and 31 were lost to
      follow-up evaluation, resulting in 212 knees available for evaluation at 6 to 10
      years. The mean follow-up period was 91 months. The mean modified Hospital for
      Special Surgery total knee score improved from 58 before surgery to 98 at the
      most recent follow-up visit. Mean patellar translation and tilt were 2.75 mm and
      3.5 degrees, respectively. There were no patellar lucencies nor loosening. Eleven
      patients (5%) underwent revision of the patellar component. Overall patellar
      survivorship was 96%. Comparatively good results can be achieved with the use of
      a metal-backed patellar component if component design, surgical technique, and
      patellar alignment are properly addressed.

PMID- 9139097
TI  - Patellar component medialization in total knee arthroplasty.
AB  - Intraoperative correction of patellar maltracking has traditionally involved the
      use of a lateral retinacular release. Problems, however, related to lateral
      retinacular release include increased postoperative pain and wound healing
      complications, compromised patellar blood flow, and longer rehabilitation. The
      purpose of this study was to assess the effect of patellar medialization in total
      knee arthroplasty. One hundred forty patients underwent total knee arthroplasty
      using the same components. Two groups of 70 patients each made up the study.
      Group 1 included patients whose patellar components were centralized on the
      patella, and group 2 consisted of patients in whom the patellar component was
      medialized to reproduce the patient's anatomic high point (ie, sagittal ridge).
      Lateral retinacular release was required in 45.5% of the patients in group 1
      compared with 17% in group 2. The technique of patellar medialization is
      described.

PMID- 9139098
TI  - Medialization of the patella in total knee arthroplasty.
AB  - Patellar complications of total knee arthroplasty remain the most common cause of
      pain and reoperation. Laboratory studies have suggested that medialization of the
      patella will improve tracking of the patella on the trochlea of the femoral
      component. The purpose of this study was to determine if clinical medialization
      of the patellar component on the patellar bone would improve tracking of the
      patella as demonstrated radiographically. Sixty-two knees were randomized so that
      31 knees had a centrally placed patellar component and 31 had the patellar
      component placed on the medial two thirds of the patellar bone. There was no
      difference between the two groups with respect to either clinical or radiographic
      results in the first year after surgery. There was no improvement compared with
      previous reports in the incidence of tilt and displacement. The one improvement
      was a reduction in the incidence of lateral release. Thus, consequences of
      lateral release such as postoperative morbidity, avascular necrosis of the
      patella, and stress fracture of the patella can be avoided. It is recommended
      that the patellar component be placed on the medial two thirds of the patella to
      reduce the occurrence of lateral release. Tracking of the patella during surgery
      can be assessed using a single suture placed at the superior pole of the patella,
      and this technique in combination with the no-thumbs test provides an additional
      means of evaluation for patellar tracking.

PMID- 9139099
TI  - Quantitative gait analysis after bilateral total knee arthroplasty with two
      different systems within each subject.
AB  - The functional behavior of two kinematically different knee arthroplasty systems
      within each subject was studied by gait analysis (three-dimensional kinematics,
      kinetics, dynamic electromyography) in five elderly patients, 2 to 5 years after
      bilateral surgery. Clinical results were good, yet gait velocity was reduced
      (range, 0.57-1.1 m/s), with a shortened stride length and a decreased duration of
      single-limb stance in all subjects. Force plate recordings revealed an undynamic
      gait with slow loading, reduced modulation of the vertical forces, and poor
      fore/aft shears. Sagittal plane knee motion during gait was reduced in all
      subjects, with trunk and pelvic compensation patterns for foot clearance. Muscle
      activity around the knee was prolonged bilaterally, with activity modulation
      related to the motion pattern. Although the stride parameters were quite
      symmetric, there was a marked asymmetry of the motion pattern, with a side-to
      side difference of peak knee flexion during stance and swing phase of up to 15
      degrees. This finding, however, was not clearly related to the type of
      prosthesis. Even within one subject, significant side-to-side variability may
      persist, which leads to asymmetry of the motion pattern, unrelated to the
      kinematic design of the implant. Other factors, such as the patella-extensor
      mechanism, ligament balancing, leg-length discrepancy, proprioception,
      continuation of a preoperative habit, or a contralateral influence, may explain
      part of the asymmetry seen in these subjects.

PMID- 9139100
TI  - Low-dose warfarin prophylaxis to prevent symptomatic pulmonary embolism after
      total knee arthroplasty.
AB  - Pulmonary embolism poses a risk to patients undergoing total knee arthroplasty.
      The selection of an appropriate prophylaxis agent and its implementation have
      been influenced by decreased duration of hospital stay and the pressures of cost
      containment. The purpose of this study was to determine the inpatient and
      outpatient pulmonary embolism rates, the number of days required to attain the
      target level of anticoagulation, and complications associated with the use of a
      low-dose warfarin prophylaxis protocol after primary and revision total knee
      arthroplasty. Between 1984 and 1993, there were 815 primary and revision total
      knee arthroplasties that received low-dose warfarin prophylaxis at our
      institution. The average time to attainment of the target level of
      anticoagulation was 3 days. The average duration of warfarin prophylaxis was 12
      days. Overall, there were a total of three symptomatic pulmonary embolisms (0.3%;
      95% confidence interval, 0.08%-1.1%). There were eight (1%) symptomatic deep vein
      thromboses (all distal). There were two deaths (0.3%), but neither one was
      secondary to a pulmonary embolism. Seventeen knees (2.5%) developed a hematoma
      after surgery, and two of these patients required drainage of the knee. Low-dose
      warfarin prophylaxis is safe and effective in preventing symptomatic pulmonary
      embolism after total knee arthroplasty.

PMID- 9139101
TI  - Prospective study of 100 consecutive Harris-Galante porous total hip
      arthroplasties. 4- to 8-year follow-up study.
AB  - This prospective study evaluates 100 consecutive Harris-Galante Porous (Zimmer,
      Warsaw, IN) noncemented femoral prostheses 4 to 8 years after surgery. Two
      femoral components were revised for aseptic loosening. The mean Harris hip score
      was 56 before surgery and 92 at final follow-up evaluation, with moderate thigh
      pain seen in 6%. Ingrowth was classified as bony (89%), stable fibrous (8%), and
      unstable (3%). A pedestal formed in 18%, measurable subsidence occurred in 22%,
      and endosteal erosion occurred in 12%. Patients with pedestal formation had a
      higher incidence of unstable growth pattern (P < .05). Patients with bony
      ingrowth had a lower mean subsidence (0.38 mm) than those with fibrous stable
      ingrowth (3 mm) and unstable ingrowth (7.5 mm) (P < .05). Thigh pain correlated
      with the type of ingrowth, and endosteal erosion with the linear polyethylene
      wear. Survival analysis was 97.5% at 8 years.

PMID- 9139102
TI  - Cementless femoral revision arthroplasty. 2- to 5-year results with a modular
      titanium alloy stem.
AB  - Seventy-five consecutive cementless femoral revision arthroplasties were
      performed, using a modular titanium alloy stem (S-ROM, Joint Medical Products,
      Stamford, CT). Sixty-six hips were available for complete follow-up evaluation at
      2 to 5 years (average, 3.4 years). Independent clinical analysis compared pre-
      with postoperative modified Harris hip scores and examined patient satisfaction.
      Independent radiographic analysis was also undertaken. There were two
      rerevisions, both for hematogenous sepsis. Of the rest, clinical scores improved
      from a preoperative value of 44 to a postoperative value of 83. Eighty-nine
      percent of patients were satisfied or very satisfied with the results of surgery.
      Fifty-two stems had solid bony ingrowth, seven were stabilized by fibrous tissue,
      and five were radiographically loose. Five-year survival, with rerevision as
      endpoint, was 96.4%.

PMID- 9139103
TI  - Abductor avulsion after primary total hip arthroplasty. Results of repair.
AB  - The results of reoperation and repair of abductor musculature avulsion that
      occurred as a complication of a primary total hip arthroplasty performed through
      an anterolateral approach were reviewed in nine patients 2 to 13.5 years (mean,
      4.8) after repair. Limp was markedly decreased in five of nine patients, and need
      for ambulatory aids also was reduced in five of the nine. Improvement continued
      for 1 to 3 years after the repair. Objectively, three of the four patients (75%)
      without significant preoperative pain had a good or excellent result, whereas
      only one of five patients (20%) with significant preoperative pain had a good or
      excellent result. In all three cases where hip instability was a presenting
      symptom, it was successfully treated. Four patients felt they were much better,
      three felt somewhat better, and two felt they gained no improvement by repair.
      This information suggests that the best indications for repair are symptoms of
      marked abductor weakness or hip instability; significant preoperative pain is
      less likely to be decreased.

PMID- 9139105
TI  - Outcome of a rotating meniscal-bearing total knee replacement (TKR) prosthesis.

PMID- 9139104
TI  - Effect of cementless acetabular cup geometry on strain distribution and press-fit
      stability.
AB  - Use of cementless acetabular cups, which are slightly larger than the reamed
      acetabulum, can provide press-fit stability without screws; however, the ideal
      cup geometry to maximize stability is not clear. Acetabular strain distribution,
      deformation, and implant stability were studied using an axisymmetric finite
      element model, and mechanical stability was assessed by testing lever-out and
      extraction forces required to displace different cup geometries from foam bones.
      The implants tested included four nonhemispheric cup geometries and 1- and 2-mm
      oversized hemispheric geometries. A nonhemispheric cup that provides a gradual
      transition from a hemisphere at the dome to a larger peripheral dimension appears
      to maximize peripheral strains and implant stability without increasing overall
      acetabular deformation as much as a larger oversized hemispheric cup.

PMID- 9139106
TI  - Orientation of the femoral sulcus in relationship to the midline of the femur.

PMID- 9139107
TI  - Patellofemoral complications following total knee arthroplasty.

PMID- 9139108
TI  - Development of a common 3D pharmacophore for delta-opioid recognition from
      peptides and non-peptides using a novel computer program.
AB  - A unified three-dimensional (3D) pharmacophore for recognition of the delta
      opioid receptor by families of structurally diverse delta-opioid ligands,
      including peptides and non-peptides, has been determined. An additional
      structural feature required for delta-selectivity was also characterized using a
      subset of these ligands that are highly selective for the delta-opioid receptor.
      To obtain these pharmacophores, we have used a recently developed computer
      program that performs systematic and automated comparisons of molecules to
      determine whether any common 3D relationships exist among candidate recognition
      moieties in high-affinity analogs. All the low-energy conformations of each
      ligand are included in these comparisons. The program developed should be
      applicable in general to molecular superimposition problems in rational drug
      design and to develop both 3D recognition and activation pharmacophores for any
      receptor for which high- and low-affinity analogs and agonists and antagonists
      have been identified.

PMID- 9139110
TI  - Prediction of the three-dimensional structure of the human Fas receptor by
      comparative molecular modeling.
AB  - The Fas antigen, a cell surface receptor belonging to the tumor necrosis factor
      receptor (TNFR) superfamily, triggers programmed cell death (apoptosis) in the
      immune system. The three-dimensional structure of Fas and molecular details of
      the interaction between Fas and its ligand are currently unknown. A three
      dimensional model of the Fas extracellular region was generated by comparative
      modeling. Inverse folding analysis suggested good sequence-structure
      compatibility of the model and thus reasonable accuracy. The model was analyzed
      in the light of information provided by studies on TNFR and CD40, another member
      of the TNFR family, and the Fas ligand binding site was predicted.

PMID- 9139109
TI  - Optimizing doped libraries by using genetic algorithms.
AB  - The insertion of random sequences into protein-encoding genes in combination with
      biological selection techniques has become a valuable tool in the design of
      molecules that have useful and possibly novel properties. By employing highly
      effective screening protocols, a functional and unique structure that had not
      been anticipated can be distinguished among a huge collection of inactive
      molecules that together represent all possible amino acid combinations. This
      technique is severely limited by its restriction to a library of manageable size.
      One approach for limiting the size of a mutant library relies on 'doping
      schemes', where subsets of amino acids are generated that reveal only certain
      combinations of amino acids in a protein sequence. Three mononucleotide mixtures
      for each codon concerned must be designed, such that the resulting codons that
      are assembled during chemical gene synthesis represent the desired amino acid
      mixture on the level of the translated protein. In this paper we present a doping
      algorithm that "reverse translates' a desired mixture of certain amino acids into
      three mixtures of mononucleotides. The algorithm is designed to optimally bias
      these mixtures towards the codons of choice. This approach combines a genetic
      algorithm with local optimization strategies based on the downhill simplex
      method. Disparate relative representations of all amino acids (and stop codons)
      within a target set can be generated. Optional weighing factors are employed to
      emphasize the frequencies of certain amino acids and their codon usage, and to
      compensate for reaction rates of different mononucleotide building blocks
      (synthons) during chemical DNA synthesis. The effect of statistical errors that
      accompany an experimental realization of calculated nucleotide mixtures on the
      generated mixtures of amino acids is simulated. These simulations show that the
      robustness of different optima with respect to small deviations from calculated
      values depends on their concomitant fitness. Furthermore, the calculations probe
      the fitness landscape locally and allow a preliminary assessment of its
      structure.

PMID- 9139111
TI  - Strategies for the determination of pharmacophoric 3D database queries.
AB  - Strategies are described for constructing pharmacophoric 3D database queries,
      based on a series of active and inactive analogs. The results are highly
      selective database queries, which are consistent with the generally accepted
      pharmacophore for a number of systems. The foundation of these strategies is the
      method of Mayer, Naylor, Motoc and Marshall [J. Comput.-Aided Mol. Design, 1
      (1987) 3] for inferring a unique binding geometry for angiotensin-converting
      enzyme (ACE) inhibitors. The strategies described here generalize their approach
      to cases where the chemical features responsible for binding are not a priori
      apparent, and to cases where the binding geometry deduced by that method is not
      unique. The key new insight, the selectivity principle, is to rank the multiple
      solutions produced by the method of Mayer et al. by their selectivity, a value
      that is related to the proportion of a database that is returned as a database
      hit list. Retrospective analyses are described for D2-antagonists, ACE
      inhibitors, fibrinogen antagonists, and beta 2-antagonists.

PMID- 9139112
TI  - A hybrid approach for addressing ring flexibility in 3D database searching.
AB  - A hybrid approach for flexible 3D database searching is presented that addresses
      the problem of ring flexibility. It combines the explicit storage of up to 25
      multiple conformations of rings, with up to eight atoms, generated by the 3D
      structure generator CORINA with the power of a torsional fitting technique
      implemented in the 3D database system UNITY. A comparison with the original UNITY
      approach, using a database with about 130,000 entries and five different
      pharmacophore queries, was performed. The hybrid approach scored, on an average,
      10-20% more hits than the reference run. Moreover, specific problems with
      unrealistic hit geometries produced by the original approach can be excluded. In
      addition, the influence of the maximum number of ring conformations per molecule
      was investigated. An optimal number of 10 conformations per molecule is
      recommended.

PMID- 9139113
TI  - MM3(96) parameterization for camptothecin analogs: an ab initio and molecular
      mechanics study.
AB  - Torsional parameters for MM3(96) were derived for the missing atom types present
      in the natural product camptothecin (CPT). Potential energy curves were
      calculated via ab initio calculations on representative compounds for dihedral
      angles containing these missing parameters. Gaussian 92 at the restricted Hartree
      Fock level of theory using the standard 6-31G** and 4-31G** basis sets, was used
      for all the quantum-mechanics calculations. Missing MM3 torsional terms were
      obtained by optimizing the V1, V2 and V3 parameters such that MM3 could reproduce
      the ab initio torsional profile. MM3 calculated molecular structures that compare
      well with the ab initio results. Using the newly developed parameters,
      conformational analyses and QSAR studies of camptothecin analogs were undertaken.
      MM3 predicts two distinct 'boatlike' conformations for the alpha-hydroxy lactone
      moiety. The low-energy lactone conformation predicted by MM3 is in general
      agreement with reported X-ray crystal structures of CPT iodoacetate and 7-ethyl
      10-(4-piperidino)piperidinylcarbonyloxy CPT HCl as well as the ab initio
      structure of a CPT-like alpha-hydroxy lactone.

PMID- 9139114
TI  - Comparative molecular field analysis and molecular modeling studies of 20-(S)
      camptothecin analogs as inhibitors of DNA topoisomerase I and
      anticancer/antitumor agents.
AB  - Conformational studies and comparative molecular field analysis (CoMFA) were
      undertaken for a series of camptothecin (CPT) analogs to correlate topoisomerase
      I inhibition with the steric and electrostatic properties of 32 known compounds.
      The resulting CoMFA models have been used to make predictions on novel CPT
      derivatives. Using the newly derived MM3 parameters, a molecular database of the
      32 CPT analogs was created. Various point atomic charges were generated and
      assigned to the MM3 minimized structures, which were used in partial least
      squares analyses. Overall, CoMFA models with the greatest predictive validity
      were obtained when both the R- and S-isomers were included in the data set, and
      semiempirical charges were calculated for MM3 minimized low-energy lactone
      structures. A cross-validated R2 of 0.758 and a non-cross-validated R2 of 0.916
      were obtained for MM3 minimized structures with PM3 ESP charges for the 32 CPT
      analogs. The derived QSAR equations were used to assign topoisomerase I
      inhibition values for compounds in this study and compounds not included in the
      original data set. Prior to its appearance in the literature, an IC50 of 103 nM
      was predicted for the 10,11-oxazole derivative. This CoMFA predicted value
      compared favorably with the recently reported value of 150 nM. The CoMFA model
      was also evaluated by predicting the activities of recently reported 11-aza CPT
      and trione derivatives. The predicted activity (IC50 = 249 nM) for 11-aza CPT
      compared well with the reported value of 383 nM.

PMID- 9139115
TI  - MS-WHIM, new 3D theoretical descriptors derived from molecular surface
      properties: a comparative 3D QSAR study in a series of steroids.
AB  - The recently proposed WHIM (Weighted Holistic Invariant Molecular) approach
      [Todeschini, R., Lasagni, M. and Marengo, E., J. Chemometrics, 8 (1994) 263] has
      been applied to molecular surfaces to derive new 3D theoretical descriptors,
      called MS-WHIM. To test their reliability, a 3D QSAR study has been performed on
      a series of steroids, comparing the MS-WHIM description to both the original WHIM
      indices and CoMFA fields. The analysis of the statistical models obtained shows
      that MS-WHIM descriptors provide meaningful quantitative structure-activity
      correlations. Thus, the results obtained agree well with those achieved using
      CoMFA fields. The concise number of indices, the ease of their calculation and
      their invariance to the coordinate system make MS-WHIM an attractive tool for 3D
      QSAR studies.

PMID- 9139116
TI  - Molecular modeling of the neurophysin I/oxytocin complex.
AB  - Neurophysins I and II (NPI and NPII) act in the neurosecretory granules as
      carrier proteins for the neurophyseal hormones oxytocin (OT) and vasopressin
      (VP), respectively. The NPI/OT functional unit, believed to be an (NPI/OT)2
      heterotetramer, was modeled using low-resolution structure information, viz. the
      C alpha carbon atom coordinates of the homologous NPII/dipeptide complex (file
      1BN2 in the Brookhaven Protein Databank) as a template. Its all-atom
      representation was obtained using standard modeling tools available within the
      INSIGHT/Biopolymer modules supplied by Biosym Technologies Inc. A conformation of
      the NPI-bound OT, similar to that recently proposed in a transfer NOE experiment,
      was docked into the ligand-binding site by a superposition of its Cys1-Tyr2
      fragment onto the equivalent portion of the dipeptide in the template. The
      starting complex for the initial refinements was prepared by two alternative
      strategies, termed Model I and Model II, each ending with a approximately 100 ps
      molecular dynamics (MD) simulation in water using the AMBER 4.1 force field. The
      free homodimer NPI2 was obtained by removal of the two OT subunits from their
      sites, followed by a similar structure refinement. The use of Model I, consisting
      of a constrained simulated annealing, resulted in a structure remarkably similar
      to both the NPII/dipeptide complex and a recently published solid-state structure
      of the NPII/OT complex. Thus, Model I is recommended as the method of choice for
      the preparation of the starting all-atom data for MD. The MD simulations indicate
      that, both in the homodimer and in the heterotetramer, the 3(10)-helices
      demonstrate an increased mobility relative to the remaining body of the protein.
      Also, the C-terminal domains in the NPI2 homodimer are more mobile than the N
      terminal ones. Finally, a distinct intermonomer interaction is identified,
      concentrated around its most prominent, although not unique, contribution
      provided by an H-bond from Ser25 O gamma in one NPI unit to Glu81 O epsilon in
      the other unit. This interaction is present in the heterotetramer (NPI/OT)2 and
      absent or weak in the NPI2 homodimer. We speculate that this interaction, along
      with the increased mobility of the 3(10)-helices and the carboxy domains, may
      contribute to the allosteric communication between ligand binding and NPI
      dimerization.

PMID- 9139118
TI  - 7th Canadian Neuro-Oncology Meeting. Montreal, Quebec, Canada, May 29-31, 1996.
      Abstracts.

PMID- 9139117
TI  - Objective models for steroid binding sites of human globulins.
AB  - We report the application of a recently developed alignment-free 3D QSAR method
      [Crippen, G.M., J. Comput. Chem., 16 (1995) 486] to a benchmark-type problem. The
      test system involves the binding of 31 steroid compounds to two kinds of human
      carrier protein. The method used not only allows for arbitrary binding modes, but
      also avoids the problems of traditional least-squares techniques with regard to
      the implicit neglect of informative outlying data points. It is seen that models
      of considerable predictive power can be obtained even with a very vague binding
      site description. Underlining a systematic, but usually ignored, problem of the
      QSAR approach, there is not one unique type of model but, rather, an entire
      manifold of distinctly different models that are all compatible with the
      experimental information. For a given model, there is also a considerable
      variation in the found binding modes, illustrating the problems that are inherent
      in the need for 'correct' molecular alignment in conventional 3D QSAR methods.

PMID- 9139119
TI  - Dipyridamole scintigraphy and intravascular ultrasound after successful coronary
      intervention.
AB  - Despite angiographically successful interventions, perfusion defects are not
      uncommonly observed in postinterventional perfusion scintigrams. The aim of this
      study was to test the hypothesis that perfusion defects after coronary
      intervention are associated with a significant residual stenosis in the treated
      vessel segment detectable by intravascular ultrasound but not by angiography.
      METHODS: Forty consecutive patients with angiographically successful coronary
      interventions were prospectively studied by intravascular ultrasound immediately
      after the intervention. Within 48 hr after the intervention all patients had
      myocardial scintigraphy using 99mTc-methoxyisobutyl-isonitrile SPECT after
      dipyridamole stress. Myocardial perfusion defects in the scintigram were assigned
      to a segmental left ventricular model and compared to the perfusion territory of
      the treated vessel estimated from the coronary angiogram. RESULTS: Twenty of 40
      patients had reversible myocardial perfusion defects. Mean ultrasound area
      stenosis was 50% in these patients and 33% in patients without perfusion defects
      (p < 0.002); ultrasound percent plaque area was 75% versus 63% (p < 0.0001),
      respectively. The best concordance between residual area stenosis and perfusion
      defects was found for an ultrasound area stenosis > or = 40%. CONCLUSION:
      Patients with stress-induced myocardial perfusion defects immediately after
      successful coronary intervention show high-grade residual stenoses that are more
      pronounced in patients with perfusion defects than in patients with normal
      postinterventional scintigrams. In addition, vessels serving myocardial regions
      with perfusion defects showed a significantly higher plaque burden indicating
      diffuse atherosclerotic changes in the vessel. The evaluation of the
      postprocedural result by intravascular ultrasound contributes to a better
      understanding of the discrepancy between the angiographic finding of a widely
      patent vessel but scintigraphic evidence of impaired perfusion.

PMID- 9139120
TI  - An examination of the relationship between form level ratings on the Rorschach
      and learning disability status.

PMID- 9139121
TI  - Ion secretion and isotonic transport in frog skin glands.
AB  - The aim of this study was to clarify the mechanism of isotonic fluid transport in
      frog skin glands. Stationary ion secretion by the glands was studied by measuring
      unidirectional fluxes of 24Na+, 42K+, and carrier-free 134Cs+ in paired frog
      skins bathed on both sides with Ringer's solution, and with 10(-5) M
      noradrenaline on the inside and 10(-4) M amiloride on the outside. At
      transepithelial thermodynamic equilibrium conditions, the 134Cs+ flux ratio,
      JoutCs/JinCs, varied in seven pairs of preparations from 6 to 36. Since carrier
      free 134Cs+ entering the cells is irreversibly trapped in the cellular
      compartment (Ussing & Lind, 1996), the transepithelial net flux of 134Cs+
      indicates that a paracellular flow of water is dragging 134Cs+ in the direction
      from the serosal- to outside solution. From the measured flux ratios it was
      calculated that the force driving the secretory flux of Cs+ varied from 30 to 61
      mV among preparations. In the same experiments unidirectional Na+ fluxes were
      measured as well, and it was found that also Na+ was subjected to secretion. The
      ratio of unidirectional Na+ fluxes, however, was significantly smaller than would
      be predicted if the two ions were both flowing along the paracellular route
      dragged by the flow of water. This result indicates that Na+ and Cs+ do not take
      the same pathway through the glands. The flux ratio of unidirectional K+ fluxes
      indicated active secretion of K+. The time it takes for steady-state K+ fluxes to
      be established was significantly longer than that of the simultaneously measured
      Cs+ fluxes. These results allow the conclusion that - in addition to being
      transported between cells - K+ is submitted to active transport along a cellular
      pathway. Based on the recirculation theory, we propose a new model which accounts
      for stationary Na+, K+, Cl- and water secretion under thermodynamic equilibrium
      conditions. The new features of the model, as compared to the classical Silva
      model for the shark-rectal gland, are: (i) the sodium pumps in the activated
      gland transport Na+ into the lateral intercellular space only. (ii) A barrier at
      the level of the basement membrane prevents the major fraction of Na+ entering
      the lateral space from returning to the serosal bath. Thus, Na+ is secreted into
      the outside bath. It has to be assumed then that the Na+ permeability of the
      basement membrane barrier (PBMNa) is smaller than the Na+ permeability of the
      junctional membrane (PJMNa), i.e., PJMNa/PBMNa > 1. The secretory paracellular
      flow of water further requires that the Na+ reflection coefficients (sigmaNa) of
      the two barriers are governed by the conditions, sigmaBMNa > 0, and sigmaBMNa >
      sigmaJMNa. (iii) Na+ channels are located in the apical membrane of the activated
      gland cells, so that a fraction of the Na+ outflux appearing downstream the
      lateral intercellular space is recirculated by the gland cells. Based on measured
      unidirectional fluxes, a set of equations is developed from which we estimate the
      ion fluxes flowing through major pathways during stationary secretion. It is
      shown that 80% of the sodium ions flowing downstream the lateral intercellular
      space is recycled by the gland cells. Our calculations also indicate that under
      the conditions prevailing in the present experiments 1.8 ATP molecule would be
      hydrolyzed for every Na+ secreted to the outside bath.

PMID- 9139122
TI  - Effect of adenosine and intracellular GTP on KATP channels of mammalian skeletal
      muscle.
AB  - We investigated the action of adenosine and GTP on KATP channels, using inside
      out patch clamp recordings from dissociated single fibers of rat flexor digitorum
      brevis (FDB) skeletal muscle. In excised patches, KATP channels could be
      activated by a combination of an extracellular adenosine agonist and
      intracellular Mg2+-ATP and GTP or GTP-gamma-S. The activation required
      hydrolyzable ATP and could be partially reversed with Mg2+, suggesting that it
      may involve a G-protein dependent phosphorylation of KATP channels. We found that
      KATP channels of the rat FDB could not be activated by Mg2+-ATP alone or by Mg2+
      ATP in the presence of extracellular adenosine. Patches whose channel activity
      had been 'rundown' by Ca2+ could not be recovered by adenosine, GTP or Mg2+-ATP.
      KATP channels activated by adenosine receptor agonists had a similar ATP
      sensitivity to those under control conditions; but adenosine appears to be able
      to switch these KATP channels from an inactive to an active mode.

PMID- 9139123
TI  - Ion channels in human THP-1 monocytes.
AB  - The THP-1 human monocytic leukemia cell line is a useful model of macrophage
      differentiation. Patch clamp methods were used to identify five types of ion
      channels in undifferentiated THP-1 monocytes. (i) Delayed rectifier K+ current,
      IDR, was activated by depolarization to potentials positive to -50 mV,
      inactivated with a time constant of several hundred msec, and recovered from
      inactivation with a time constant approximately21 sec. IDR was inhibited by 4
      aminopyridine (4-AP), tetraethylammonium (TEA+), and potently by charybdotoxin
      (ChTX). (ii) Ca-activated K+ current (ISK) dominated whole-cell currents in cells
      studied with 3-10 micron [Ca2+]i. ISK was at most weakly voltage-dependent, with
      reduced conductance at large positive potentials, and was inhibited by ChTX and
      weakly by TEA+, Cs+, and Ba2+, but not 4-AP or apamin. Block by Cs+ and Ba2+ was
      enhanced by hyperpolarization. (iii) Nonselective cation current, Icat, appeared
      at voltages above +20 mV. Little time-dependence was observed, and a panel of
      channel blockers was without effect. (iv) Chloride current, ICl, was present
      early in experiments, but disappeared with time. (v) Voltage-activated H+
      selective current is described in detail in a companion paper (DeCoursey &
      Cherny, 1996. J. Membrane Biol. 152:2). The ion channels in THP-1 cells are
      compared with channels described in other macrophage-related cells. Profound
      changes in ion channel expression that occur during differentiation of THP-1
      cells are described in a companion paper (DeCoursey et al., 1996. J. Membrane
      Biol. 152:2).

PMID- 9139124
TI  - Voltage-activated proton currents in human THP-1 monocytes.
AB  - Depolarization-activated H+-selective currents were studied using whole-cell and
      excised-patch voltage clamp methods in human monocytic leukemia THP-1 cells,
      before and after being induced by phorbol ester to differentiate into macrophage
      like cells. The H+ conductance, gH, activated slowly during depolarizing pulses,
      with a sigmoidal time course. Fitted by a single exponential following a delay,
      the activation time constant, tauact was roughly 10 sec at threshold potentials,
      decreasing at more positive potentials. Tail currents upon repolarization decayed
      mono-exponentially at all potentials. The tail current time constant, tautail,
      was voltage dependent, decreasing with hyperpolarization from 2-3 sec at 0 mV to
      approximately 200 msec at -100 mV. Surprisingly, although tauact depended
      strongly on pHo, tautail was completely independent of pHo. H+ currents were
      inhibited by Zn2+. Increasing pHo or decreasing pHi shifted the voltage
      activation relationship to more negative potentials, tending to activate the gH
      at any given voltage. Studied in excised, inside-out membrane patches, H+
      currents were larger and activated much more rapidly at lower bath pH (i.e.,
      pHi). In THP-1 cells differentiated into macrophages, the H+ current density was
      reduced by one-half, and tauact was slower by about twofold. The properties of H+
      channels in THP-1 cells and in other macrophage-related cells are compared.

PMID- 9139125
TI  - Ion channel expression in PMA-differentiated human THP-1 macrophages.
AB  - Ion channel expression was studied in THP-1 human monocytic leukemia cells
      induced to differentiate into macrophage-like cells by exposure to the phorbol
      ester, phorbol 12-myristate 13-acetate (PMA). Inactivating delayed rectifier K+
      currents, IDR, present in almost all undifferentiated THP-1 monocytes, were
      absent from PMA-differentiated macrophages. Two K+ channels were observed in THP
      1 cells only after differentiation into macrophages, an inwardly rectifying K+
      channel (IIR) and a Ca2+-activated maxi-K channel (IBK). IIR was a classical
      inward rectifier, conducting large inward currents negative to EK and very small
      outward currents. IIR was blocked in a voltage-dependent manner by Cs+, Na+, and
      Ba2+, block increasing with hyperpolarization. Block by Na+ and Ba2+ was time
      dependent, whereas Cs+ block was too fast to resolve. Rb+ was sparingly permeant.
      In cell-attached patches with high [K+] in the pipette, the single IIR channel
      conductance was approximately 30 pS and no outward current could be detected. IBK
      channels were observed in cell-attached or inside-out patches and in whole-cell
      configuration. In cell-attached patches the conductance was approximately 200-250
      pS and at potentials positive to approximately 100 mV a negative slope
      conductance of the unitary current was observed, suggesting block by
      intracellular Na+. IBK was activated at large positive potentials in cell
      attached patches; in inside-out patches the voltage-activation relationship was
      shifted to more negative potentials by increased [Ca2+]. Macroscopic IBK was
      blocked by external TEA+ with half block at 0.35 mM. THP-1 cells were found to
      contain mRNA for Kv1.3 and IRK1. Levels of mRNA coding for these K+ channels were
      studied by competitive PCR (polymerase chain reaction), and were found to change
      upon differentiation in the same direction as did channel expression: IRK1 mRNA
      increased at least 5-fold, and Kv1.3 mRNA decreased on average 7-fold. Possible
      functional correlates of the changes in ion channel expression during
      differentiation of THP-1 cells are discussed.

PMID- 9139126
TI  - pH-induced proton permeability changes of plasma membrane vesicles.
AB  - In vivo studies with leaf cells of aquatic plant species such as Elodea nuttallii
      revealed the proton permeability and conductance of the plasma membrane to be
      strongly pH dependent. The question was posed if similar pH dependent
      permeability changes also occur in isolated plasma membrane vesicles. Here we
      report the use of acridine orange to quantify passive proton fluxes. Right-side
      out vesicles were exposed to pH jumps. From the decay of the applied DeltapH the
      proton fluxes and proton permeability coefficients (PH+) were calculated. As in
      the intact Elodea plasma membrane, the proton permeability of the vesicle
      membrane is pH sensitive, an effect of internal pH as well as external pH on PH+
      was observed. Under near symmetric conditions, i.e., zero electrical potential
      and zero DeltapH, PH+ increased from 65 x 10(-8) at pH 8.5 to 10(-1) m/sec at pH
      11 and the conductance from 13 x 10(-6) to 30 x 10(-4) S/m2. At a constant pHi of
      8 and a pHo going from 8.5 to 11, PH+ increased more than tenfold from 2 to 26 x
      10(-6) m/sec. The calculated values of PH+ were several orders of magnitude lower
      than those obtained from studies on intact leaves. Apparently, in plasma membrane
      purified vesicles the transport system responsible for the observed high proton
      permeability in vivo is either (partly) inactive or lost during the procedure of
      vesicle preparation. The residue proton permeability is in agreement with values
      found for liposome or planar lipid bilayer membranes, suggesting that it reflects
      an intrinsic permeability of the phospholipid bilayer to protons. Possible
      implications of these findings for transport studies on similar vesicle systems
      are discussed.

PMID- 9139128
TI  - Dry cleaning, some chlorinated solvents and other industrial chemicals. Lyon,
      France, 7-14 February 1995.

PMID- 9139127
TI  - The SpTRK gene encodes a potassium-specific transport protein TKHp in
      Schizosaccharomyces pombe.
AB  - Complementary DNAs involved in potassium transport in Schizosaccharomyces pombe
      were selected by complementation of defective K+ uptake in a trk1 trk2 mutant of
      Saccharomyces cerevisiae. Here we describe the SpTRK gene that encodes a protein
      of 833 amino acids. The predicted structure contains 12 putative membrane
      spanning domains and resembles various high- and low-affinity systems for K+
      transport in yeasts and plants. TKHp, the product of SpTRK exhibits high homology
      to TRK1 and TRK2 of Saccharomyces cerevisiae as well as to HKT1 of Triticum
      aestivum, but is not related to HAK1 of another ascomycete, Schwanniomyces
      occidentalis, suggesting that different routes for potassium uptake evolved
      independently. This protein is a potassium-specific transporter since functional
      analysis of the SpTRK complemented mutant strain of Sacch. cerevisiae revealed
      potassium transport affinities and uptake characteristics similar to those
      obtained in wild-type Sch. pombe. Patch-clamp analysis in the whole-cell mode
      confirmed the TKHp-mediated inward current in the complemented strain. The inward
      current increased by acidification of the extracellular medium thereby suggesting
      a mechanism of K+H+ cotransport. The inward current is not detectable when
      external K+ is substituted by Na+, documenting a distinct cation specificity of
      the protein.

PMID- 9139129
TI  - Dry cleaning.

PMID- 9139130
TI  - Trichloroethylene.

PMID- 9139131
TI  - [Guideline for the clinical evaluation fo anti-infective agents].

PMID- 9139132
TI  - [Case of allergic bronchopulmonary mycosis caused by Schizophyllum commune].

PMID- 9139133
TI  - [Case of allergic bronchopulmonary mycosis caused by Schizophyllum commune].

PMID- 9139134
TI  - [Case of allergic bronchopulmonary aspergillosis without complication of asthma
      attack].

PMID- 9139135
TI  - [Case of allergic bronchopulmonary mycosis with positive result of intradermal
      candida test].

PMID- 9139136
TI  - [Surgical case of allergic bronchopulmonary aspergillosis].

PMID- 9139137
TI  - [Case of allergic bronchopulmonary aspergillosis with bronchiectasis --long-term
      follow-up study].

PMID- 9139139
TI  - [Present status and future prospect of study on hypersensitivity pneumonitis in
      Japan].

PMID- 9139138
TI  - [Role of fungi in pathogenesis of adulthood bronchial asthma].

PMID- 9139140
TI  - [International guidelines for the clinical evaluation of anti-infective drugs].

PMID- 9139141
TI  - [A contagiousness study in 3071 familial contacts of tuberculosis patients].
AB  - BACKGROUND: The study of contacts of patients with tuberculosis is an important
      preventive measure which helps to identify the risk factors for contagion, to
      detect new cases of the disease early and to break the epidemiological chain of
      transmission. MATERIAL AND METHOD: Three thousand and seventy-one contacts of 635
      patients with tuberculosis were studied in our department over a period of 6
      years. With the aid of uni- and multivariate analyses we established the
      importance of different factors in the appearance of tuberculous disease and
      infection in contacts. RESULTS: There were 1,341 tuberculin positive contacts
      (44%). The proportion increased in relation to the degree of the relationship and
      the bacillary density of the index case. A hundred and seventy-six new cases of
      tuberculosis were diagnosed among the contacts (5.7%). To study the risk factors
      for contagion, we analyzed the characteristics of 322 patients with positive
      sputum smears and their 1,623 contacts; 124 new cases were diagnosed among them
      (124/176; 70%). The most important factors for contagion in the multivariate
      analysis were the closer relationship (odds ratio [OR] = 8.32; confidence
      interval [Cl] 95% = 3.9-17.6), greater TST reaction of contacts (OR = 4.43; Cl
      95% = 2.5-7.7), presence of more than 10 bacilli per microscopic field in the
      sputum samples of the index case (OR = 1.97; Cl 95% = 1.1-3.3), male contacts (OR
      = 1.86; Cl 95% = 1.2-2.7) and those younger than 15 years (OR = 1.58; Cl 95% =
      1.01-2.45). Conversely, the sex of the index case and the history of previous
      tuberculosis in contacts did not influence the contagion. CONCLUSIONS: The study
      of contacts offers a high yield in the diagnosis of new tuberculosis cases,
      because the incidence of the disease is much higher than that of the general
      population. Moreover, it allows the detection of newly infected subjects in whom
      the application of chemoprophylaxis prevents the development of the disease, and
      thus the epidemiologic chain of transmission is broken.

PMID- 9139142
TI  - [The long-term results on arterial pressure and kidney function after the
      percutaneous transluminal dilatation of renal artery stenosis].
AB  - BACKGROUND: The purpose of this study was to evaluate the clinical results
      analyzing the cure, improvement and failure rates of percutaneous transluminal
      angioplasty (PTA) in patients with the diagnosis of renovascular hypertension
      with special reference to those with atherosclerotic vascular disease, according
      to their age, and their effect on blood pressure control and renal function.
      PATIENTS AND METHODS: In 93 hypertensive patients with a mean age of 43.4 years
      123 renal artery PTA were performed: Twenty-six patients older than 50 years and
      eleven with 50 years or less had atherosclerosis, 27 fibromuscular dysplasia and
      a mixed disease was found in one patient. Twenty-eight patients with renal
      transplant were diagnosed as having arterial graft stenosis. RESULTS: After renal
      PTA, there was a significant decrease in blood pressure in all cases. Patients
      with atherosclerotic renal vascular disease showed a decrease in systolic
      pressure (SP) from 168 +/- 19 before PTA to 154 +/- 8 mmHg at 96 months (p <
      0.001) and diastolic (DP) from 113 +/- 10 before PTA to 90 +/- 4 mmHg at 96
      months (p < 0.001) respectively after the procedure. Significant differences were
      also observed in patients with fibromuscular dysplasia. Most patients with renal
      transplant arterial stenosis had less than five years of follow-up and SP and DP
      decreased from 162 +/- 18 and 109 +/- 8 mmHg before PTA, to 147 +/- 10 (p <
      0.001) and 91 +/- 7 mmHg (p < 0.001) at 12 months after dilation respectively.
      Clinical improvement was achieved in 91% of patients with atherosclerosis at 96
      months and fifty percent of the patients with fibromuscular dysplasia were cured
      after the same period from the time of PTA. Twelve months after the renal
      transplant artery dilation was achieved a clinical improvement in 81% and a cure
      rate in 6% of the patients. Ostial lesions comprised the majority of blood
      pressure benefit failures. There was no significant improvement in renal function
      immediately after renal artery dilation except in those patients with
      fibromuscular dysplasia. Residual stenosis greater than 75% was present in 15
      patients after the first PTA. Complications were seen in 4.8% and were related to
      renal failure and vessel dissection. CONCLUSION: Angioplasty is effective in the
      long-term management of high arterial blood pressure and may preserve renal
      function according to renal artery disease.

PMID- 9139143
TI  - [Nutritional status assessment in diabetes mellitus secondary to chronic
      alcoholic pancreatitis].
AB  - BACKGROUND: Diabetes mellitus secondary to alcoholic chronic pancreatitis (DM
      ACP) represents 0.5-2% of all cases of diabetes mellitus (DM) and shows
      predominantly symptoms related to malnutrition instead of cardinal clinical signs
      of diabetes. The aim of this study was to try to further characterize the
      features of the malnutrition in patients with pancreatic insufficiency. PATIENTS
      MATERIAL AND METHODS: We selected 40 patients (39 males and 1 female) meeting
      clinical, functional and morphological diagnostic criteria of DM-ACP which
      received a nutritional assessment that included estimation on fat and proteic
      body compartments being classified as caloric, proteic or mixed malnutrition.
      RESULTS: 29 patients (72.5%) showed some kind of malnutrition. The most frequent
      type was mixed (proteic-caloric) malnutrition found in 19 of them (47.5%).
      Caloric malnutrition was present in 6 (15%) and mainly proteic in 4 (10%). Only
      11 patients with DM-ACP in our series showed a normal nourishment state.
      CONCLUSIONS: Large prevalence of mixed malnutrition in DM-ACP patients may be
      related to malabsorption of macronutrients (especially proteins and fat) due to
      exocrine insufficiency and misuse of nutrients as a result of the characteristic
      hypoinsulinemia showed by these patients.

PMID- 9139145
TI  - [Tuberculosis. An especially contagious disease].

PMID- 9139144
TI  - [The loss of reliability in data extraction from clinical histories: the source
      of the flaws and the usefulness of training].
AB  - BACKGROUND: Clinical-epidemiological research often requires using data stored in
      clinical records. There is a paucity of systematic studies of errors in the data
      extraction process from clinical records in the medical literature. In order to
      assess the increment of reliability in data extraction from clinical records due
      to training, we estimate the degree of agreement in the data extraction process
      from clinical records of rheumatoid arthritis patients. MATERIAL AND METHODS:
      Test-retest, quasi-experimental study. A random sample of clinical records was
      selected from a rheumatoid arthritis patients register. The degree of agreement
      between the two observers, before and after a specific training, was estimated
      with kappa and intraclass correlation coefficients. RESULTS: Following
      standardized ranking of the degree of agreement, we observed that 5 out 19 (26%)
      studied variables improved significantly after training and 14 (74%) remained
      with the same degree of agreement or did not change significantly. At the end of
      the study, only two variables received a degree of agreement less than good
      whereas six did so before training. The improvement was noted in the clinical
      variables. CONCLUSIONS: It is possible to have a systematic approach to the
      source of errors in the use of data from clinical records. The training of
      observers has a significant impact on the degree of agreement and therefore
      improves reliability. The training in the extraction and management of clinical
      information may contribute to the improvement of validity and reliability of
      observations in medical practice.

PMID- 9139146
TI  - [The association of beta zero-thalassemia and Hb D Punjab in a family of Indian
      origin. The second case reported in Spain].
AB  - The present report described the hematologic and molecular study of the second
      case of Hb D-Punjab associated with a beta zero-thalassemia found in Spain and
      the first case in which the mutations have been identified at molecular level. A
      family from India is studied, which is constituted by mother (I2) and 3 children
      (II1, II2 and II3). The molecular characterization of the hemoglobinopathy was
      made by electrophoretic and chromatographic techniques and confirmed by
      sequencing of the beta-globin gene. The mutation causer of the beta-thalassemia
      was studied by PCR-ARMS. The mother (I2) and one of her child (II2) are carriers
      of the gene for beta zero-thalassemia owing to the frameshift CD 8/9 mutation (+
      G). Other of them (II1) is heterozygous for Hb D-Punjab without beta-thalassemia
      association. The third child (II3) knows a double heterozygote state for Hb D
      Punjab/beta zero-thalassemia (hemoglobin D-thalassemia). In spite of the patient
      with hemoglobin D-thalassemia has 94.5% of Hb D, without Hb A, the hematologic
      picture belongs to thalassemia trait with moderate haemolytic anemia, intense
      microcytosis and hypochromia and numerous target cells. This hematologic picture
      discloses the mildness of the Hb D-Punjab, but the reliable responsible for the
      phenotype is the disbalance in the synthesis of globin chains, because of
      frameshift CD 8/9 mutation (+ G) beta zero-thalassemia mutation.

PMID- 9139147
TI  - [The treatment of tuberculosis. Yesterday, today...and tomorrow].

PMID- 9139148
TI  - [The usefulness of determining carcinoembryonic antigen in the bile for the
      prognosis of the development of hepatic metastases following the resection of
      colorectal cancer].

PMID- 9139149
TI  - [Thrombophlebitis in a patient with acute Q fever and anticardiolipin
      antibodies].

PMID- 9139150
TI  - [Serological and molecular HLA typing in Andalusian patients with Behcet's
      disease. Genetic-clinical correlations].

PMID- 9139151
TI  - [High-dosage chemotherapy in breast cancer].

PMID- 9139152
TI  - [Alcohol consumption in schoolchildren].

PMID- 9139153
TI  - [The reason for medical consultations in patients with psychiatric diseases:
      somatization phenomena and suicide attempts].
AB  - BACKGROUND: The objectives of the study are to document the frequency of use of
      the general medical services by psychiatric patients, to measure how many
      consultations are due to somatization and suicide attempts and to know the
      existence of possible differences between psychiatric inpatients and outpatients
      in relation to the reason of medical consultation. MATERIAL AND METHODS:  DESIGN:
      retrospective study. Site: Manchester Royal Infirmary, a university third level
      hospital in Manchester (United Kingdom). PATIENTS: patients from the psychiatric
      department seen during the period from July 1st to December 31st in 1992 (n =
      1,012 patients). RESULTS: The percentage of patients that consults a
      medical/surgical department in one year is 27.5%, 25.2% of outpatients and 36.3%
      of inpatients. Non-medical reasons are 42.3% of these consultations: 30.4%
      somatization phenomena and 10.8% suicide attempts. The frequency of somatization
      in psychiatric patients (30.4%) is similar to that described in non-psychiatric
      patients. The psychiatric inpatients that are referred to a medical department as
      inpatients show a significant lower rate of somatization (2.2%) and a higher rate
      of suicide (35.5%). CONCLUSIONS: On fourth of psychiatric patients consult a
      medical department in one year and more than 40% of these consultations are not
      due to somatic diseases. The frequency of somatization in psychiatric patients is
      similar to the observed in other patients. Psychiatric inpatients that are also
      medical inpatients in one year constitute a specific high risk group.

PMID- 9139154
TI  - [The validity of basal blood glucose in the control of non-insulin-dependent
      diabetic patients].
AB  - BACKGROUND: To validate basal glucemia as a control method for non-insulin
      dependent diabetes mellitus, and to determine the cut-off point that best
      characterizes good control. PATIENTS AND METHODS: A transversal, observational
      study of 256 patients who participated in a diabetes mellitus follow-up program
      during 1993. In the study, glucemia validity indicators were evaluated after
      making 2 X 2 tables and ROC (receiver operating characteristic) curves for the
      different values. Control values of glycated hemoglobin was used as to define a
      good (< 6.5%) and moderate (< 8%). RESULTS: The values of glucemia considered to
      be "good" as regards control (from 80 to 110 mg/dl, 4.4-6.05 mmol/dl) have good
      sensitivity (from 97.3% to 100%) and negative predictive values (from 85.7% to
      100%) but extremely bad specificity (from 3.8% to 22.7%) and only moderate
      positive predictive values (from 59.5% to 64.1%) in reference to values of
      glycated hemoglobin of 6.5%. The same occurs for 8% as regards sensitivity (from
      98.6% to 100%), negative predictive value (from 96.4% to 100%) and specificity
      from 2.1% to 14.5%). Positive predictive value worsens (from 27.8% to 30.3%). The
      most effective and most accurate values of glucemia in the ROC curves are 150
      mg/dl (8.25 mmol/l) if the control of glycated hemoglobin is good, and 170 mg/dl
      (9.35 mmol/l) if it is moderate. CONCLUSIONS: The glucemia control figures
      recommended by consensus produce false positives when they are compared to
      glycated hemoglobin. In the analysis of effectiveness and ROC curves greater
      accuracy is obtained with glucemia values that are slightly higher than those
      recommended.

PMID- 9139155
TI  - [The underreporting of perinatal mortality: 10 years' experience of active
      surveillance in Barcelona].
AB  - BACKGROUND: Perinatal mortality is considered a good effectiveness health care
      indicator during pregnancy, deliver and early perinatal period. The aims of this
      investigation were to describe the magnitude and tendency of underreporting
      perinatal mortality in Barcelona, Spain from 1985 to 1994 and to determine
      underreporting predictive variables. SUBJECTS AND METHODS: Perinatal deaths
      between 1985 and 1994 were studied according to WHO international statistics
      criteria and deaths from 1988 to 1994 were also studied according to the WHO
      national statistics criteria. Sources of information were: Statistical Deaths
      Certificates and the Active Surveillance Registry that collect information about
      perinatal deaths directly from hospitals. A perinatal death was considered
      underreported if it was registered in the Active Surveillance Register but not in
      the Statistical Death Certificate. RESULTS: 24.5% perinatal deaths were
      underreported from 1985 to 1995 (according to international statistics criteria)
      and 24.9% from 1988 to 1994 (according national statistics criteria). In both
      periods underreporting decreased. Deaths in the first 24 hours of live (OR = 1.8;
      CI 95% = 1-3), newborns weight between 1,000 and 1,499 g (OR = 1.5; CI 95% = 0.6
      3.8), hospitals with mortality registry (OR = 4; CI 95% = 2.2-7.1) and the first
      years of the study (OR = 0.7; CI 95% = 0.7-0.8) were predictive of
      underreporting. CONCLUSIONS: Underreporting perinatal deaths decreased during the
      study period. Deaths of newborns with low birth weight and who lived less than 24
      hours were more underreported. The work developed by Active Surveillance Registry
      contributed to the decense of underreporting perinatal deaths.

PMID- 9139157
TI  - ["Soma" and "psyche". Six of one, half a dozen of the other?].

PMID- 9139156
TI  - [A study of 30 patients with bacteremia due to Campylobacter spp].
AB  - BACKGROUND: To get better knowledge about clinical and bacteriological features
      in Campylobacter spp. bacteremia. PATIENTS AND METHODS: Over a period of 8 years
      (1987-1994) we prospectively analyzed underlying diseases, predisposing factors,
      clinical manifestations, complications and outcome of patients with Campylobacter
      spp. bacteremia. The study took place in an urban third-level teaching hospital.
      Antibiogram was tested in all the strains isolated. RESULTS: We identified 30
      cases of Campylobacter spp. bacteremia (26 due to C. jejuni and 4 due to C.
      fetus). Seventy-three percent of the patients were male and the mean age +/- SD
      of all the patients was 52 +/- 19 years. Ninety percent of patients had some kind
      of immunodepression related to immunosuppressive therapy or to underlying
      diseases, especially liver cirrhosis and HIV infection. All patients had fever
      and 40% complained of intestinal symptoms before bacteremia. Mortality rate in
      patients with C. jejuni bacteremia was 30.8% (8 patients) during the admission,
      the death was directly related to bacteremia in 11.5% (3 patients). In all the
      fatal cases C. jejuni was resistant to empirical antibiotherapy instituted. In
      contrast, none of the patients with C. fetus bacteremia died. We detected an
      increasing ciproflaxin resistance in C. jejuni strains during this period which
      reached to 75% in the last years. Antimicrobial susceptibility to erythromycin
      and aminoglucosids was kept in all the strains. CONCLUSIONS: Campylobacter spp.
      bacteremia has a remarkable mortality rate, probably related to immunosuppressive
      underlying diseases in affective patients. In our institution we detected an
      increasing fluoroquinolone resistance over the years while susceptibility to
      erythromycin and aminoglucosids was maintained.

PMID- 9139158
TI  - [The genetic diagnosis of hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
      deficiency. A study of 12 cases].
AB  - Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency is transmitted
      as an X-linked recessive trait. Female carriers are asymptomatic and the carrier
      diagnosis is usually performed by determining HGPRT activity in hair roots. This
      technique does not allow a non-carrier state diagnosis with absolute certainty
      and has other limitations such as obtaining non-viable hair roots. The knowledge
      of the genetic mutation in three Spanish families with HGPRT deficiency, enabled
      us to perform the genetic diagnosis of the carrier state in 10 female subjects at
      risk and one female fetus. The genetic diagnosis has been performed by analyzing
      the differences between the mutant and the normal allele with respect to the
      restriction pattern. When the restriction pattern showed no differences, this has
      been created by directed mutagenesis. With this methodology we confirmed that a
      newborn of a known carrier female of HGPRT deficiency was healthy. In all cases
      the diagnosis could be established with great fiability in a mean time of 24 to
      48 hours. We report the first genetic diagnosis of the carrier state for the
      HGPRT deficiency performed in Spain.

PMID- 9139159
TI  - [Non-typhoid salmonellosis and human immunodeficiency virus (HIV) infection].

PMID- 9139160
TI  - [Nontraumatic rhabdomyolysis due to oral poisoning by doxylamine succinate].

PMID- 9139161
TI  - [Acute tetraplegia in a patient with Sjogren's syndrome].

PMID- 9139162
TI  - [Oophoritis due to cytomegalovirus in a female AIDS patient].

PMID- 9139163
TI  - [Primary care team coordinators and chiefs of service].

PMID- 9139164
TI  - [Intracranial hypertension in postoperative hypoparathyroidism].

PMID- 9139165
TI  - [An update on the tuberculosis situation in Spain].

PMID- 9139166
TI  - Exercise and bone mineral density in mature female athletes.
AB  - An understanding of the relationship between weight-bearing activity and bone
      mineral density (BMD) is important in devising strategies to maximize and
      maintain skeletal strength in the female population, particularly those entering
      menopause. Three contrasting groups (N = 20) of mature female athletes (42-50 yr)
      with long-term (> 20 yr) histories of significant training and performance in
      their chosen sport were studied cross-sectionally. The groups were: (i) high
      impact sport (netball/basketball; HIGH), (ii) medium impact sport (running/field
      hockey; MED) and (iii) a nonimpact sport (swimming; NON) and (iv) a nonsport
      control group (CON; N = 20). Whole body and regional BMD and body composition
      (fat and lean mass) were measured by dual-energy x-ray absorptiometry. Isometric
      strength of dominant arm flexors and leg extensors was measured by a strain
      tensiometer. With an alpha level of significance of 0.05, HIGH showed
      significantly greater whole body and regional leg BMD than NON or CON. MED
      registered higher values than CON for whole body and regional leg BMD. Only HIGH
      had significantly greater leg strength than CON. Regional arm BMD was
      significantly greater in all exercising groups compared with CON, but no
      significant difference in arm strength was found between any groups. The athletic
      groups all had significantly lower body fat and higher height-corrected lean mass
      than CON. Height-corrected lean mass, height and leg extensor strength, but not
      calcium intake, arm flexor strength or body fat, were significant predictors of
      whole body and regional arm and leg BMD. Using the significant predictors as
      covariates, the impact groups (HIGH/MED) had significantly higher whole body BMD
      than CON. HIGH also had significantly higher whole body BMD than NON and both
      impact groups were greater than NON in regional leg BMD. Results suggest that
      females who participate regularly in the premenopausal years in high impact
      physical activity tend to have higher BMD than nonathletic controls.

PMID- 9139167
TI  - Left ventricular function during exercise testing and training.
AB  - Left ventricular function (LVEF) deteriorates during incremental exercise (GXT)
      in patients with ischemia (+ISCH). Left ventricular (LV) functional response
      during steady-state exercise, typical of that used in exercise training, are
      unknown. We compared LVEF in patients with documented coronary heart disease
      (CHD) who either had (+) or did not have (-) ISCH, and in healthy volunteers
      (CONTROL) during GXT and steady state. First pass RNA was performed during
      upright cycle GXT at rest (R), at the ventilatory threshold (VT), and at maximal
      exercise (Max); and during steady state at the workload associated with VT after
      10, 20, and 30 min of exercise. RNA allowed measurement of ejection fraction (EF)
      and wall motion (WM); ISCH was mild, angina being relieved by momentary
      reductions in workload during steady state. Although +ISCH demonstrated the
      expected deterioration in LV function during GXT (decreased EF, abnormal WM)(EF =
      58 to 56 to 54%), there was no evidence for progressive deterioration of LV
      function during steady state despite the presence of mild ISCH (56 to 56 to 54 to
      54%). In -ISCH and CONTROL there were normal responses of EF during GXT (43 to 51
      to 51% and 59 to 65 to 61%) and steady state (43 to 51 to 53 to 51% and 59 to 65
      to 68 to 69%). We conclude that mild ischemia may be tolerated during steady
      state exercise at levels consistent with exercise training without progressive
      deterioration of LV function.

PMID- 9139168
TI  - Interval training in patients with severe chronic heart failure: analysis and
      recommendations for exercise procedures.
AB  - This study analyzes a new exercise training procedure, which includes interval
      exercise training on cycle ergometer (IntCT) (30-s work phases/60-s recovery
      phases) and on treadmill (60-s work and recovery phases each). Training was
      applied for 3 wk in 18 patients with severe chronic heart failure (CHF) ((mean +/
      SEM) age 52 +/- 2 yr, ejection fraction 21 +/- 1%). Peak VO2 was increased from
      12.2 +/- 0.7 to 14.6 +/- 0.7 ml-kg-1 min-1 owing to training (P < 0.001). A
      specific steep ramp test (work rate increments 25 W.10 s-1) was developed to
      derive exercise intensity for work phases in IntCT, which was 50% of the maximum
      work rate achieved. Steep ramp test was performed at the start of the study to
      determine the initial training work rate, then weekly to readjust it. Since the
      maximum work rate achieved from this test increased weekly (144 +/- 10 W -->172
      +/- 10 W-->200 +/- 11 W; P < 0.001), the training work rate also increased (72 +/
      4 W-->86 +/- 6 W-->100 +/- 7 W; P < 0.001). Physical responses to IntCT were
      measured. There was no significant change in heart rate, blood pressure, and
      ratings of perceived exertion (RPE) using a Borg Scale between the first and the
      third week of training (heart rate 88 +/- 3 b.min-1; blood pressure 115 +/- 4/80
      +/- 2 mm Hg; leg fatigue 12 +/- 1; dyspnea 10 +/- 1). Mean lactate concentration
      (1.70 +/- 0.09 mmol-1-1) indicated an overall aerobic range of training
      intensity. When compared with the commonly used intensity level of 75% peak VO2
      from an ordinary ramp test (work rate increments 12.5 W.min-1), the performed
      training work rate was more than doubled (240%; P < 0.0001) while cardiac stress
      was lower (86%; P < 0.01). Values of norepinephrine and epinephrine as well as of
      RPE corresponded to those measured at 75% peak VO2. Interval exercise training is
      thus recommended for selected patients with CHF as it allows intense exercise
      stimuli on peripheral muscles with minimal cardiac strain. Using a steep ramp
      test, training work rate can be determined and readjusted weekly during initial
      training period.

PMID- 9139169
TI  - Rat tendon morphologic and functional changes resulting from soft tissue
      mobilization.
AB  - Augmented Soft Tissue Mobilization (ASTM) is a new non-invasive soft tissue
      mobilization technique which has been used successfully to treat a variety of
      musculoskeletal disorders. The purpose of this study was to determine the effects
      of ASTM therapy on the morphological and functional characteristics of enzyme
      induced injured rat Achilles tendons. Four groups of five rats were allocated as
      follows: (A) control, (B) tendinitis, (C) tendinitis plus ASTM, and (D) ASTM
      alone. Collagenase injury was induced, and the surgical site was allowed to heal
      for 3 wk. ASTM was performed on the Achilles tendon of groups C and D for 3 min
      on postoperative days 21, 25, 29, and 33 for a total of four treatments. Gait
      data were gathered prior to each treatment. The Achilles tendons of each group
      were harvested 1 wk after the last treatment. Specimens were prepared for light
      and electron microscopy, and immunostaining for type I and type III collagen and
      fibronectin was performed. Light microscopy showed increased fibroblast
      proliferation in the tendinitis plus ASTM treatment group. Although healing in
      rats may not translate directly to healing in humans, the findings of this study
      suggest that ASTM may promote healing via increased fibroblast recruitment.

PMID- 9139170
TI  - Facial cooling-induced bradycardia: attenuating effect of central command at
      exercise onset.
AB  - Facial cooling (FC) elicits a marked bradycardia at rest that appears to be
      reduced during exercise. This study was done to delineate the effects of exercise
      mediated central command from those of muscle afferent feedback and sympathetic
      stimulation on the attenuation of the bradycardic effect of FC during the onset
      of exercise. Ten healthy subjects (26 +/- 2 yr) were exposed to FC under five
      different conditions: 1) seated rest on the cycle ergometer, 2) onset of mild
      exercise (resting HR + 20 beats.min-1), 3) onset of moderate exercise (resting HR
      + 50 beats.min-1), 4) seated rest on the ergometer during electrical stimulation,
      and 5) seated rest on the ergometer during a cold immersion test (CT) (one hand
      immersed in an ice slurry at 0 degree C). The two exercise intensities were
      presumed to provide different degrees of central command. Electrical stimulation
      of the quadriceps was assumed to provide isolated muscle afferent feedback, while
      the CT served as a sympathetic stimulus. Beat-by-beat data were recorded for HR
      and mean arterial blood pressure for the duration of each test (50 s), and a
      rating of perceived pain was taken after each FC. FC elicited significant
      increases in mean arterial pressure during mild and moderate exercise compared
      with resting control (P < 0.05) and during moderate exercise compared to exercise
      without FC (P < 0.05). Mean decreases in HR during FC were similar for resting
      control (-12 +/- 3 beats.min-1), electrical stimulation (-10 +/- 3 beats.min-1),
      and CT (-9 +/- 3 beats.min-1). The HR response to FC during mild exercise (-7 +/-
      2 beats.min-1) was significantly different (P < 0.05) from the rest condition;
      however, there was no significant bradycardia (-2 +/- 2 beats.min-1; P > 0.05)
      during onset of moderate exercise. These findings suggest that the magnitude of
      cold face-induced bradycardia may be attenuated at exercise onset by neural
      signals related to the higher levels of central motor command associated with
      heavier exercise.

PMID- 9139171
TI  - The effect of ultrasound on collagen synthesis and fibroblast proliferation in
      vitro.
AB  - Ultrasound has been applied therapeutically to accelerate connective tissue
      healing although there is little direct scientific evidence to support its use.
      This investigation was conducted to determine the effects of ultrasound on the
      rate of collagen synthesis and cell proliferation using cultured fibroblasts
      derived from Achilles tendons of neonatal rats. Ultrasound (intensity = 0.4 W.cm
      2; frequency = 1 MHz) was applied to experimental cells growing as monolayers in
      culture flasks. Ultrasound had no effect on the rate of collagen synthesis by
      control fibroblasts over a period of 9 d. The addition of vitamin C to culture
      media stimulated collagen synthesis to the same extent in both control and
      ultrasound-treated cultures. Partial digestion of cell matrices with collagenase
      (used to simulate injury) resulted in an approximately 20% increase in the rate
      of collagen synthesis. Synthesis was further increased with ultrasound treatment
      (50-67%). For example, after a single ultrasound treatment, the rate of collagen
      synthesis was 3.0 +/- 0.4 pg.micrograms-1 DNA.h-1 in cultures treated with
      collagenase, compared with 1.8 +/- 0.3 pg.micrograms-1 DNA.h-1 in collagenase
      treated cultures not treated with ultrasound and 1.4 +/- 0.3 pg.micrograms-1
      DNA.h-1 in controls. Ultrasound applied to preconfluent cultures resulted in
      significant increases in the rate of thymidine incorporation and DNA content.
      Three daily ultrasound treatments caused a 100% increase in the rate of thymidine
      incorporation and a 28% increase in DNA content. The results indicate that
      ultrasound stimulates collagen synthesis in tendon fibroblasts in response to an
      injury of the connective tissue matrix and that ultrasound stimulates cell
      division during periods of rapid cell proliferation.

PMID- 9139173
TI  - Effect of exhaustive exercise stress on the cytokine response.
AB  - Fifteen athletes were investigated 24 h before, 1 h after, and 20 h after an
      exhaustive exercise stress test (mean duration 68 min). Testing for cytokines was
      done in serum, urine, and the supernatants of whole blood cell cultures, which
      were stimulated with lipopolysaccharide (LPS), concanavalin A (Con A), or
      phythaemagglutinin (PHA). Elevated levels of interleukin 6 (IL-6) and soluble IL
      2 receptor (sIL-2R) were found 1 h after the run in both serum and urine samples.
      TNF-alpha in serum was also increased, whereas IL-2 in urine was decreased after
      the exercise. All other testings in serum and urine (including IFN-gamma) gave
      borderline or negative results. In cell cultures, the LPS-induced release of the
      inflammatory cytokines TNF-alpha, IL-1, and IL-6 was suppressed 1 h after
      exercise. Also, the Con-A-induced and LPS-induced release of IFN-gamma, and the
      PHA-induced release of IL-2 were suppressed 1 h after exercise. In contrast, Con
      A-induced release of IL-2 was mildly increased after the run. We conclude that
      exercise of the intensity and duration described here causes an activation of the
      immune system, which is immediately counter-regulated. Twenty hours after the
      exercise, most of the observed changes were back to pre-exercise levels,
      indicating only a short duration for this suppressive counter-regulation.

PMID- 9139172
TI  - Influence of the level of dietary lipid intake and maximal exercise on the immune
      status in runners.
AB  - Chronic exercise and high fat diets are associated with immune suppression. This
      study compares cellular immune responses at rest and after maximal exercise in
      runners after eating diets comprised of 17% low fat (LF), 32% medium fat (MF),
      and 41% high fat (HF) (4 wk each). VO2max increased significantly from the 17% to
      41% fat diet. The leukocyte cell counts were significantly increased after
      exercise. In men, significantly higher proliferative response to
      phytohemagglutinin (PHA) (P < 0.004) was observed with MF diet, while response to
      pokeweed mitogen (PWM) was significantly decreased by MF and HF diets. The number
      of CD8+ (suppressor) T cells was significantly higher in men and exercise
      increased it significantly, while CD4+ (helper) T cells were not affected.
      Natural killer cells number was significantly increased 2.5 fold by exercise and
      with increase in dietary fat. The production of IL-2 by peripheral blood
      mononuclear cells was significantly higher in men (P < 0.0001) and increasing
      dietary fat significantly increased IL-2 production (P < 0.001). In men, exercise
      decreased the level of the proinflammatory cytokines (IL-1, IL-6 and TNF-alpha),
      whereas in women, with the exception of MF diet for IL-6, exercise had no effect.
      This study indicates that short, intense bouts of exercise in runners training 40
      miles.wk-1 have mixed effects on the immune system. A high percentage of fat
      intake (41%) did not have any deleterious effects on the immune system of the
      well-trained runners.

PMID- 9139174
TI  - Dietary red pepper ingestion increases carbohydrate oxidation at rest and during
      exercise in runners.
AB  - The effects of dietary hot red pepper on energy metabolism at rest and during
      exercise were examined in long distance male runners 18-23 yr of age. A
      standardized meal was given on the evening prior to the experiment. The subjects
      had a meal (2720 kJ) with or without 10 g of hot red pepper for breakfast. During
      rest (2.5 h after meal) and exercise (pedaling for 1 h at 150 W, about 60%
      VO2max, using cycling ergometry), expired gasses and venous blood were collected.
      The meal with hot red pepper significantly elevated respiratory quotient and
      blood lactate levels at rest and during exercise. Oxygen consumption at rest was
      slightly but nonsignificantly higher in the hot red pepper meal at 30 min after
      the meal. Plasma epinephrine and norepinephrine levels were significantly higher
      in those who had only hot red pepper at 30 min after the meal. These results
      suggest that hot red pepper ingestion stimulates carbohydrate oxidation at rest
      and during exercise.

PMID- 9139175
TI  - Fat distribution, physical activity, and cardiovascular risk factors.
AB  - The purpose of this study was to report the relationship between fat
      distribution, physical activity (PA), and cardiovascular disease (CVD) risk
      factors. Percent fat, computed tomography intra-abdominal adipose tissue (IAF),
      anthropometrics, Baecke activity questionnaire, and CVD risk (blood pressure,
      cholesterol, HDL, HDL2, HDL3, IDL, LDL, VLDL, and triglycerides) were evaluated
      in 137 men 30-71 yr old. IAF was consistently more highly related to CVD risk
      than other fat distribution variables including percent fat and waist:hip ratio
      (r = 0.3-0.45). IAF was significantly related to CVD risk after adjusting for
      other fat distribution variables. With the exception of the sum of biceps,
      triceps, thigh, and calf skinfolds (peripheral skinfolds), which was negatively
      related to CVD risk, no other fat distribution variable had consistent
      significant partial correlations with CVD risk. PA was related to IAF after
      adjusting for peripheral skinfolds, but PA was not related to peripheral
      skinfolds after adjusting for IAF, indicating more active men have relatively low
      IAF. IAF was related to CVD risk after adjusting for PA, but PA was not related
      to CVD risk after adjusting for IAF. These results indicate that IAF is directly
      related to CVD risk while the lower CVD risk found with more active men is more
      directly related to the low IAF found in more active men.

PMID- 9139176
TI  - Optimization of walking in children.
AB  - Previous work demonstrated that adults naturally adopt a walking frequency to
      optimize physiological cost, symmetry, and stability. Furthermore, the optimal
      frequency is predictable using the force-driven harmonic oscillator (FDHO) model.
      However, no studies have established the developmental processes of optimization
      in children. Thus, the purposes of this study were to examine the predictability
      of the preferred stride frequency (PSF) and optimization features of 3- to 12-yr
      old children using the FDHO model. Forty-five children and nine adults were
      measured for anthropometric data to calculate the predicted frequency. They later
      walked at three frequencies (PSF, PSF +25%, and PSF -25%) at a constant speed on
      a treadmill. The results indicated that the FDHO model was accurate in predicting
      the preferred frequency of children (prediction error < 0.07 s). We identified
      three stages of learning in the development of optimization: an early
      manifestation of sensitivity to resonant frequency, the subsequent development of
      ability to modulate walking frequency, and the final establishment of an adult
      optimization form at age seven. Our findings suggest that walking development may
      be determined by the dynamic cooperation of physiological, neural, and
      musculoskeletal systems with respect to the environmental context.

PMID- 9139177
TI  - Metabolic efficiency during arm and leg exercise at the same relative
      intensities.
AB  - This study was conducted to compare gross efficiency (GE), net efficiency (NE),
      work efficiency (WE), and delta efficiency (DE) between arm crank and cycle
      exercise at the same relative intensities. Eight college-aged males underwent two
      experimental trials presented in a randomized counterbalanced order. During each
      trial subjects performed three intermittent 7-min exercise bouts separated by 10
      min rest intervals on an arm or semirecumbent leg ergometer. The power outputs
      for the three bouts of arm crank or cycle exercise corresponded to 50, 60, and
      70% of the mode-specific VO2peak. GE, NE, and WE were determined as the ratio of
      Kcal.min-1 equivalent of power output to Kcal.min-1 of total energy expended,
      energy expended above rest and energy expended above unloaded exercise,
      respectively. DE was determined as the ratio of the increment of Kcal.min-1 of
      power output above the previous lower intensity to the increment of kcal.min-1 of
      total energy expended above the previous lower intensity. GE and NE did not
      differ between arm crank and cycle exercises. However, WE was lower (P < 0.05)
      during arm crank than cycle exercise at 50, 60, and 70% VO2peak. DE was also
      lower (P < 0.05) during arm crank than cycle exercise at delta 50-60 and at delta
      60-70% VO2peak. It is concluded metabolic efficiency as determined by work and
      delta efficiency indices was lower during arm crank compared with cycle exercise
      at the same relative intensities. These findings add to the understanding of the
      difference in metabolic efficiency between upper and lower body exercise.

PMID- 9139178
TI  - Reliability of variables in the kinematic analysis of spring hurdles.
AB  - The purpose of this study was to investigate the reliability of kinematic
      variables in spring hurdles and to find out how many trials are needed to achieve
      reliable data. Seven British National level athletes in sprint hurdles were
      videotaped and all eight trials of each athlete were digitized from two camera
      views to produce three dimensional coordinates. The reliability of 28 kinematic
      variables across eight trials ranged from 0.54 to 1.00 for females and from 0.00
      to 0.99 for males. The number of trials needed to reach a certain reliability
      level was evaluated using Spearman-Brown prophecy formula, and in the worst case
      (horizontal velocity lost for males) 78 trials would be needed to reach 0.90
      reliability. The results showed reasonably high reliability, and the values for
      the female trials were generally higher than the male trials. The relative height
      of the hurdles enforces a more demanding clearance for males that can lead to
      increased variation within the subjects and thus lowered reliability.
      Subsequently, the results indicate that often more than one trial is needed to
      provide accurate quantitative results of the technique.

PMID- 9139179
TI  - Metabolic profile of high intensity intermittent exercises.
AB  - To evaluate the magnitude of the stress on the aerobic and the anaerobic energy
      release systems during high intensity bicycle training, two commonly used
      protocols (IE1 and IE2) were examined during bicycling. IE1 consisted of one set
      of 6-7 bouts of 20-s exercise at an intensity of approximately 170% of the
      subject's maximal oxygen uptake (VO2max) with a 10-s rest between each bout. IE2
      involved one set of 4-5 bouts of 30-s exercise at an intensity of approximately
      200% of the subject's VO2max and a 2-min rest between each bout. The accumulated
      oxygen deficit of IE1 (69 +/- 8 ml.kg-1, mean +/- SD) was significantly higher
      than that of IE2 (46 +/- 12 ml.kg-1, N = 9, p < 0.01). The accumulated oxygen
      deficit of IE1 was not significantly different from the maximal accumulated
      oxygen deficit (the anaerobic capacity) of the subjects (69 +/- 10 ml.kg-1),
      whereas the corresponding value for IE2 was less than the subjects' maximal
      accumulated oxygen deficit (P < 0.01). The peak oxygen uptake during the last 10
      s of the IE1 (55 +/- 6 ml.kg-1.min-1) was not significantly less than the VO2max
      of the subjects (57 +/- 6 ml.kg-1.min-1). The peak oxygen uptake during the last
      10 s of IE2 (47 +/- 8 ml.kg-1.min-1) was lower than the VO2max (P < 0.01). In
      conclusion, this study showed that intermittent exercise defined by the IE1
      protocol may tax both the anaerobic and aerobic energy releasing systems almost
      maximally.

PMID- 9139180
TI  - Lactate exchange and removal abilities in rowing performance.
AB  - The relationships between individual performance and lactate exchange and removal
      abilities were studies in 12 male rowers all subjected to three measurements on a
      rowing ergometer. An incremental exercise carried out to determine the maximal
      oxygen uptake (VO2max) and the corresponding maximal aerobic power (Pamax), a
      2500-m all-out test where the mean work rate (P2500) represented the individual
      performance, and a 6-min 90% Pamax exercise designed to assess the lactate
      kinetics during the following 90 min passive recovery were performed. The lactate
      recovery curves were fitted to the bi-exponential time function: La(t) = La(O) +
      A1(1-e-gamma 1.t) + A2(1-e-gamma 2.t). The velocity constants gamma 1 and gamma 2
      denote the lactate exchange and removal abilities, respectively. The mean value
      of P2500 sustained by the rowers was 376 +/- 41W (106 +/- 5% of Pamax (P2500%).
      P2500 was positively correlated with gamma 2 (P < 0.05). gamma 1 and gamma 2
      explained 67% of the P2500 variance. P2500% was also correlated with gamma 2 (P <
      0.01). These results suggest that a better performance on the rowing ergometer is
      associated with improved lactate exchange and removal abilities. Furthermore, the
      ability to row at high relative work rates was correlated with an increased
      lactate removal ability. Training-induced adaptations could explain the high
      gamma 1 and gamma 2 displayed by the present rowers.

PMID- 9139181
TI  - Detection of ventilatory threshold using near infrared spectroscopy in men and
      women.
AB  - The onset of anaerobic (lactate) metabolism during incremental exercise, which
      may be a result of an imbalance between tissue oxygen supply and demand, has been
      associated with the gas exchange ventilatory threshold (VT). This study was
      designed to examine whether near infrared spectroscopy (NIRS) could be used to
      detect the VT in healthy subjects. Twenty-one men and 19 women completed
      incremental cycle ergometry during which NIRS measurements were obtained from the
      right vastus lateralis and gas exchange measurements were monitored
      simultaneously using a metabolic cart. The VT was identified from the metabolic
      data by the V-slope method and from NIRS data as the intensity at which tissue
      absorbency crossed the resting baseline value observed immediately prior to the
      initiation of exercise. Pearson correlations for the relative oxygen uptake and
      power output observed for the two methods of detecting VT were 0.90 and 0.88,
      respectively, in men and 0.89 and 0.86, respectively, in women (P < 0.01). No
      significant differences were observed between the two methods of detecting VT for
      any of the physiological responses (P > 0.05). No significant (P > 0.05) gender
      differences were observed in muscle oxygenation values at the VT, 32% in men and
      38% in women. These results validate the use of NIRS as an alternate noninvasive
      method for detecting VT during cycle exercise in healthy subjects.

PMID- 9139182
TI  - Heart rate reserve is equivalent to %VO2 reserve, not to %VO2max.
AB  - Percentage of heart rate reserve (%HRR) is widely considered to be equivalent to
      % of maximal oxygen consumption (%VO2max) for exercise prescription purposes.
      However, this relationship has not been established in the literature, and a
      theoretically stronger case can be made for an equivalency between %HRR and %VO2
      Reserve (%VO2R) (i.e., the difference between resting and maximal VO2). The
      current study hypothesized that %HRR is equivalent to %VO2R, not %VO2max, and
      that the discrepancy between %HRR and %VO2max would be inversely proportional to
      fitness level. Sixty-three adults performed incremental maximal exercise tests on
      an electrically braked cycle ergometer. HR and VO2 at rest, at the end of each
      stage of exercise, and at maximum were used to perform linear regressions on %HRR
      versus %VO2max, and %HRR versus %VO2R for each subject. For %HRR versus %VO2max,
      the mean intercept and slope were -11.6 +/- 1.0 and 1.12 +/- 0.01, respectively,
      which were significantly different (P < 0.001) from 0 and 1, respectively. For
      %HRR versus %VO2R, the mean intercept and slope were -0.1 +/- 0.6 and 1.00 +/-
      0.01, respectively, which were not distinguishable from the line of identity.
      There was a significant (P < 0.01) inverse relationship between fitness level
      (VO2max) and the discrepancy between %HRR and %VO2max. In conclusion, %HRR should
      not be considered equivalent to %VO2max. Rather, %HRR is equivalent to %VO2R, and
      this relationship should be used in exercise prescription.

PMID- 9139183
TI  - Non-exercise VO2max estimation for physically active college students.
AB  - This study sought to develop a maximal oxygen consumption (VO2max) regression
      model derived strictly from self-reported non-exercise (N-EX) predictor
      variables. The VO2max (mean +/- SD; 44.05 +/- 6.6 ml.kg-1.min-1) of 100
      physically active college students (50 females, 50 males), aged 18 to 29 yr, was
      measured using a treadmill protocol and open circuit calorimetry. Questionnaire
      based predictor variables used in the N-EX regression model included (a) the
      subject's perceived functional ability (PFA) to walk, jog, or run given
      distances, (b) habitual physical activity (PA-R) data, (c) body mass index (BMI),
      and (d) gender. BMI (kg.m-2) was computed from self-reported body weight in
      pounds and self-reported body height in feet and inches. The questionnaire-based
      N-EX regression model (R = 0.85, SEE = 3.44 ml.kg-1.min-1) developed in this
      study exceeded the accuracy of previously developed N-EX regression models and is
      comparable to many exercise-based regression models in the literature. Cross
      validation using PRESS (predicted residual sum of squares) statistics
      demonstrated minimal shrinkage (R = 0.84, SEE = 3.60 ml.kg-1.min-1) of the
      present regression model. The PFA data were useful in explaining observed VO2max
      variance (squared partial r2 = 0.155, P < 0.0001) and enhanced the ability of the
      N-EX regression model to accurately predict criterion VO2max. These results
      suggest that a questionnaire-based N-EX regression model provides a valid and
      convenient method for predicting VO2max in physically active college students.

PMID- 9139184
TI  - [In Africa, urban malaria is the malaria of tomorrow].

PMID- 9139185
TI  - [African osteoperiostitis].

PMID- 9139186
TI  - [Yellow fever: modern aspects of an ancient malady].

PMID- 9139187
TI  - [Ivory Coast modernizes its health system].

PMID- 9139188
TI  - [Travelers meeting with the unexpected].

PMID- 9139189
TI  - [Planning for evacuation of the severely traumatised patient in Africa].

PMID- 9139190
TI  - [Globalization of transmissible disease surveillance: a new approach to
      international cooperation].

PMID- 9139191
TI  - [The return of trypanosomiasis: a new challenge from a forgotten disease].

PMID- 9139192
TI  - [Evaluation of the Ivory Coast sentinel surveillance system for antimalarial drug
      sensitivity].
AB  - This study was performed to assess the sentinel surveillance system on malaria
      resistance in Cote d'Ivoire using a new method. Evaluation was based on
      documentation describing routine products and on activity reports obtained from
      the surveillance system. A qualitative approach was used to assess system design
      and quantitative approach to assess its operation. Degree of satisfaction with
      evaluation criteria was scored on a scale of 1 to 5. Score reproducibility in
      this study was good. Overall the system was considered as satisfactory. The
      strong points of the system are relevance, functions, sustainability, and data
      quality. The weak points are poor planning, overcentralization, and underuse of
      information. Correction of these weakness will require concentration by all
      parties at the national level involved in the surveillance system. The evaluation
      method used was simple, cheap and reproducible and thus could serve as an
      alternative approach for evaluation of sentinel surveillance systems in areas
      with scarce resources.

PMID- 9139193
TI  - [HIV seroprevalence in adults with pulmonary tuberculosis in Yaounde, Cameroon].
AB  - To determine current seroprevalence of HIV in adult patients with pulmonary
      tuberculosis in Yaounde, Cameroon, we prospectively studied 671 consecutive
      patients aged 15 years or more, admitted to the chest clinic of Jamot Hospital
      from July 1994 to December 1995. All sera were screened for HIV antibodies by
      ELISA and positive sera were confirmed by western blotting. A total of 113 of the
      671 patients (16.8%) were positive. There was no significant difference between
      the overall rate of HIV seropositivity in men and women. However 20.5% of women
      aged 15 to 24 years were HIV positive as compared to only 5.6% of men in the same
      age group (p < 0.01). The seroprevalence rate was also significantly higher in
      patients living in urban than rural areas (p < 0.02). There was no significant
      difference between HIV seropositive and seronegative patients with respect to
      marital status, level of education, or criminal record. Blood transfusion had
      been performed in 9.7% of seropositive patients as compared to 4.5% of
      seronegative patients (p = 0.02).

PMID- 9139194
TI  - [A method to estimate the nutritional value of food sold by street vendors].
AB  - Food bought outside the house from woman vendors accounts for a significant part
      of the nutritional intake in urban areas in Africa regardless of age and socio
      economic category of the inhabitants. Despite this fact outdoor food consumption
      is not adequately taken into account in relevant studies. The great variability
      in space and time of recipes used by vendors makes it very difficult to estimate
      the nutritional value of the food consumed. The purpose of the present study
      which was carried out on some female vendors in Bamako, Mali, was to evaluate a
      simplified assessment method. Assessment is based on information that vendors can
      easily provide: recipes including ingredients and quantities and sales figures.
      The results obtained were coherent and appeared to be fairly accurate. However
      they have to be confirmed by laboratory analyses. Compared to average per capita
      wages in Mali, the income of these female vendors appears to be high.

PMID- 9139195
TI  - [Cost effectiveness of local regional anesthesia in a remote area].
AB  - Loco-regional anesthesia techniques are considered as a simple and economic
      solution to problems posed by anesthesia in developing countries. However the
      cost benefits of some techniques are reduced by cardiovascular effects that
      affect the quantity and nature of peroperative vascular filling usually necessary
      during general anesthesia. The purpose of the present study was to ascertain the
      relative costs of these methods by comparing the quantity of crystalloid solution
      and blood administered during loco-regional anesthesias and general anesthesias
      in a general hospital center in Africa. In a retrospective cohort of 1050
      consecutive patients operated on in the Surgery and Gynecology/Obstetrics
      Departments of the A. Sice Hospital in Pointe Noire (Congo), 495 included in a
      study comparing perimedullary anesthesia and general anesthesia. The total volume
      of solution and blood administered to the patients during the procedure was
      studied in function of the type of anesthesia and surgery performed. Results
      showed that the amount of crystalloid solution administered during peridural and
      spinal anesthesia tended to be higher. This difference was significant only for
      prostate surgery. Use of epidural anesthesia did not increase the quantity of
      fluid modified gelatin and blood transfused in this series. It was also observed
      that 55% of patients who underwent peridural anesthesia required further
      intravenous anesthesia as opposed to 18.8% of patients who underwent spinal
      anesthesia. These findings indicate that loco-regional anesthesia performed under
      standardized conditions does not significantly change the quantity and nature of
      preoperative filling usually necessary during general anesthesia. Thus these
      techniques can be considered as cost-effective in developing countries even
      though the long period necessary for practitioners to learn them results in a
      transient increase in cost. A prospective study by surgical groups with
      experience using loco-regional anesthesia is needed to confirm this study.

PMID- 9139196
TI  - [Microfilarial loads of onchocerca and experimental vectorial capacity of
      Simulium soubrense-Simulium sanctipauli group in the forest zone of Ivory Coast].
AB  - Mass treatment programs using ivermectin are now beginning in forest areas and
      simuli will soon be feeding on individuals with low microfilarial loads (probably
      < 10). Most previous reports have involved higher mean loads (range: 14-6950. The
      purpose of this study was to ascertain the impact of low microfilarial loads on
      the number of infecting larvae present at the end of a parasite cycle in the
      Simulium soubrense-Simulium sanctipauli group and on availability for
      transmission to man by inoculation. Tests were carried out on five subjects from
      a forest area of southwest Ivory Coast who were infected with onchocerciasis and
      presented mean microfilarial loads of 1, 5, 10, 20, and 100. Findings showed a
      direct correlation between microfilarial load (1, 5, 20, and 100) and intake of
      microfilaria per dissected female. Similarly there was a correlation between
      microfilarial loads (1, 5, 10, 20, and 100), quantity of infected females, and
      number of infecting larvae per infected female. Parasite output was variable but
      decreased as microfilarial load increased. This study suggests that the
      experimental vectorial capacity of simuli is similar in subjects presenting
      onchocerciasis with high and low microfilarial loads.

PMID- 9139197
TI  - [Etiopathogenic, ultrasonographic and prognostic features of postpartum
      cardiomyopathy].
AB  - Peripartum cardiomyopathy is a classic but uncommon entity in African women about
      which there is little etiologic understanding. From January 1990 to March 1996 a
      series of 30 cases of peripartum cardiomyopathy was collected at the Principal
      Hospital in Dakar, Senegal. Peripartum cardiomyopathy was defined as the
      occurrence of cardiac insufficiency in a woman with no previous history of heart
      disease, during the period between the second and twentieth weeks after delivery
      confirmed by ultrasound evidence of dilated cardiomyopathy. The overall incidence
      of peripartum cardiomyopathy during the study period was 30 out of 1200
      deliveries. The mean age of the women in the study was 34 years and mean parity
      was 5.2. In 13.3% of cases births involved twins. There were no predisposing
      socio-economic or climatic factors. The clinical picture was severe cardiac
      failure in 80.3% of cases and left ventricular insufficiency in 16.6%. In all
      cases ultrasound findings were typical of dilated cardiomyopathy. Serum selenium
      and vitamin B1 levels were normal. Measurements of T CD4 and CD8 in eight
      patients were normal. Conversion enzyme inhibitors were administered to twenty
      patients. Complete remission was achieved in 14 patients, three patients died,
      and thirteen patients presented ultrasonic evidence of persistent dilated
      cardiomyopathy. One patient relapsed after a subsequent delivery. These findings
      are in agreement with previous reports concerning the clinical and prognostic
      features of peripartum cardiomyopathy in Africa.

PMID- 9139198
TI  - [Idiopathic central serous chorioretinopathy: two case reports observed in Togo].
AB  - Central serous chorioretinopathy is due to accumulation of serous fluid between
      the sensory retina and pigmented epithelium. Our perusal of the literature did
      not turn up any reports on this topic in Black Africa. The disorder was observed
      in 2 patients from Togo who presented with unilateral reduction in visual acuity.
      Initially suspected by the presence of a macular lesion on the fundus and by
      ophthalmoscopic examination, diagnosis was confirmed by angiofluorography.
      Angiofluorography is the method of choice and the low incidence of this eye
      disorder in Black Africa is probably due to the poor availability of this method.
      Although the two patients in this study responded to corticosteroid therapy,
      treatment usually requires laser photocoagulation to eliminate the site of
      abnormal transudation and create a choroidal adhesion. In this regard recent
      studies indicate that the primary mechanism underlying this disorder is
      multifocal or diffuse hyperpermeability of the choroidal vessels.

PMID- 9139199
TI  - [Envenomation by exotic snakes].
AB  - Snake bite envenoming in tropical areas affects an estimated one million people
      according to the World Health Organization. Two studies showed that annual
      mortality is between 30,000 and 50,000 people. Clinically cobra and viper
      envenoming are the most well known but several other snakes cause characteristic
      manifestations allowing species-specific diagnosis. Immuno-enzymatic tests are a
      useful diagnostic tool that is currently expanding but remains available only in
      developing countries because of cost. Treatment consists mainly of serotherapy in
      the most severe cases. Use of purified products and fragments active specifically
      on toxins and enzymes is both safer and more effective. Heparinotherapy should be
      used only when indicated by clinical manifestations and hemostasis testing.
      Management of envenoming must be organized in function of antivenom
      availabilities in a given region. Future improvements in immuno-enzymatic tests
      and antivenoms should allow more successful treatment of severe snake bite
      envenoming.

PMID- 9139200
TI  - [Hepatitis C epidemiology in the world].
AB  - Development of screening tests for hepatitis C virus (HCV) has enabled study to
      ascertain hypotheses concerning the epidemiology of non-A, non-B hepatitis.
      Phylogenic analysis shows that HCV genotypes 1, 2, and 3 are responsible for most
      cases of chronic hepatitis C in developing countries whereas genotypes 4, 5, and
      6 are involved in other areas of the world. Our understanding of the transmission
      of this virus is also improving and transfusion and addiction-related
      transmission have now been confirmed. However many questions remain about other
      routes involving sex, intrafamilial contact, and mother-to-infant transmission.
      After transfusion there is a period of serological latency during which infection
      cannot be detected by PCR and which raises the problem of post-transfusion
      seronegative hepatitis. Current knowledge of the natural history of the disease
      is limited to the chronic hepatitis stage. New methods must be developed to
      detect and study the disease in cohorts with early stage disease. Since knowledge
      about worldwide prevalence is also limited, further studies are needed in the
      general population in different geographical areas taking into account the fact
      that southern and eastern Europe, Japan, and Black Africa are high prevalence
      zones with rates above 1.5%.

PMID- 9139201
TI  - [History of the public health policy in Chad 1900-1995].
AB  - Public health policy in Chad began after colonization in 1899 and remained under
      the control of French Army Medical Corps for a long time. Military doctors shared
      their time between treating service personnel and indigenous people entitled
      Medical Assistance and making rounds in their sector. Since independence public
      health in the country has been based on a two-pronged association including fixed
      facilities (hospitals and dispensaries) and mobile services such as the Endemic
      Disease Unit whose most notable success was control of sleeping sickness in the
      southern part of the country. Over the years Chad has built up a national medical
      staff comprising 150 physicians. A medical school was opened in N'Djamena in 1990
      and paramedical personnel are now trained at the National School for Public
      Health. War and lack of funds interrupted mobile services and there is presently
      a recrudescence of sleeping sickness. Since 1990 the World Health Organization
      has imposed its views and primary care is now available for all. However, it is
      now too early to judge the efficacity of this program in Chad.

PMID- 9139202
TI  - [Mycobacterium ulcerans: in vitro sensitivity of a strain isolated in Ivory
      Coast].

PMID- 9139203
TI  - [Rhabdomyolysis during Shigella flexneri shigellosis].

PMID- 9139204
TI  - [True hermaphroditism in Senegal: cultural and religious influences on sexual
      orientation].

PMID- 9139205
TI  - [A case of strangulated intestinal obstruction by the vermiform appendix].

PMID- 9139206
TI  - [Malaria and marketing policy].

PMID- 9139207
TI  - [Cutaneous leishmaniasis and leishmania species in French Guiana].

PMID- 9139208
TI  - [Problems in diagnosis and therapy of malignant pleural mesothelioma].
AB  - The incidence of malignant pleural mesothelioma increased continuously during
      recent years. This is related to widespread use and processing of asbestos in the
      last decades. Characteristical symptoms like dyspnea, cough and thoracic pain are
      common in almost all pulmonal diseases. Therefore the possible occurrence of a
      pleural tumor is often neglected. This leads to a delay between onset of symptoms
      and the establishment of diagnosis. With X-ray and computed tomography 80% of the
      pleural tumors can be proved. Only in few cases the histopathological analysis of
      the pleural fluid leads to diagnosis. However, thoracoscopy or thoracotomy remain
      the most reliable means of obtaining a definitive tissue diagnosis. At the time
      of operation advanced stages are found in many cases, therefore palliative
      surgery is indicated. Due to high morbidity and mortality pleuropneumonectomy
      should be done only in selected patients. Pleurectomy or pleurodesis is often
      sufficient to release patients' symptoms. Chemotherapy and radiation have not
      proven effective in controlling malignant mesothelioma. In conclusion pleural
      mesothelioma remains a tumor with a very poor prognosis. Long term survival is
      occasional even in case of multimodal treatment.

PMID- 9139209
TI  - [Terminal care medicine--basic principles and perspectives].

PMID- 9139211
TI  - [Multi-national clinical therapy studies. Design, management and costs].
AB  - The development of new drugs requires increasingly the performance of large
      multinational clinical trials (MCT) with a common protocol. They must be planned
      when the demonstration of a hypothesis, which requires specific conditions (for
      example availability of patients with rare diseases, a particular infrastructure
      or expert knowledge in trial centers) has to be proven in an acceptable time. Our
      own experience has shown that such multinational trials are more time-consuming
      in their preparation and their analysis than multicenter trials which are run in
      one country. MCTs are associated with complex problems due to many differences in
      medical culture, treatment strategies, administrative guidelines, etc., between
      countries. When possible MCTs should be realized in countries and centers with
      relatively similar medical practices. A global coordination is necessary to
      control the progress of the trial in the different countries. The major
      requirements for the successful realisation of an MCT, from the writing of the
      first draft of the protocol until the publication of the results, are a well
      coordinated multidisciplinary team and an effective project management.

PMID- 9139210
TI  - [Polyneuropathies in monoclonal gammopathy of undetermined significance: initial
      manifestation of a lymphoma].
AB  - BACKGROUND: Monoclonal gammopathies-including so-called monoclonal gammopathies
      of undetermined significance-MGUS-may cause polyneuropathies, even if
      immunoglobulin concentrations are within a normal range. CASE REPORT: We report
      on a patient with a rapidly progressive polyneuropathy with severe motor
      disturbances in whom a small amount of a monoclonal IgM kappa cryoglobulin was
      found. Only by extensive, repeatedly performed diagnostic procedures could
      scattered lymphoma cells be detected. Nonspecific immunosuppression had been
      unsuccessful but eventually a more specific chemotherapy led to an almost
      complete, sustained recovery. CONCLUSION: This case shows that in patients with a
      polyneuropathy of uncertain etiology monoclonal immunoglobulins should be looked
      for and that a MGUS can precede a lymphoma. Therefore these, patients with a MGUS
      and clinical deterioration despite conventional immunosuppressive treatment
      should undergo large-scale diagnostic check-up to make sure that the chance for
      an adequate chemotherapy is taken.

PMID- 9139212
TI  - [Treatment of euthyroid struma. Comparable volume reduction with 400 micrograms
      iodine, 100 micrograms levothyroxine combined with 100 micrograms iodine or
      individually dosed levothyroxine].
AB  - AIM: In patients with euthyroid goitre, the efficacy of treatment with 400
      micrograms iodine and 100 micrograms levothyroxine combined with 100 micrograms
      iodine was compared to that of the previous standard of therapy, individually
      dosed levothyroxine. PATIENTS AND METHODS: A total of 78 patients presenting with
      euthyroid diffuse goitre (> or = 25 ml) were prospectively enrolled, randomised
      and treated for 6 months. The course of thyroid volume was followed using thyroid
      volumetry. RESULTS: Data of 69 patients were included in the final evaluation (57
      women, 12 men, age 31 +/- 1 years, thyroid volume 31.5 +/- 1.4 ml, 23 per
      treatment group). In the patients treated with individually dosed levothyroxine,
      the thyroid volume decreased by about 39% (95%-confidence limit [CL]-31% to 
      41%). However, the volume reductions achieved in the patients treated with 400
      micrograms iodine or 100 micrograms levothyroxine/100 micrograms iodine were not
      significantly different (p = 0.35, variance analysis, mono-iodine -34%, 95%-CL 
      29% to -43%, 100 micrograms levothyroxine/100 micrograms iodine -39%, 95%-CL -32%
      to -45%). CONCLUSIONS: In patients with euthyroid diffuse goitre, treatment with
      mono-iodine or combination of levothyroxine with iodine should have principally
      the same status as the previous standard of therapy, individually dosed
      levothyroxine. In the view of the authors, its preferential treatment with mono
      iodine appears most reasonable.

PMID- 9139213
TI  - [Egr-1 transcription factor regulates the growth of glomerular mesangium cells].
AB  - BACKGROUND: The transcriptional regulator Early growth response gene-1 (Egr-1) is
      rapidly and transiently induced by various mitogens in cultured rat mesangial
      cells (MCs). METHOD AND RESULTS: Here we show Egr-1 induction in an in vivo model
      of mesangioproliferative glomerulonephritis (GN). A 14.9-fold increase in Egr-1
      mRNA was observed 6 days after disease induction. A concomitant increase in Egr-1
      protein was demonstrated by immunocytochemistry. Egr-1 was mainly localized to
      the nuclei of cells in mesangial localization. To test whether Egr-1 directly
      regulated MC proliferation, we preincubated cultured MCs with antisense
      oligonucleotides directed against Egr-1. The platelet-derived growth factor
      (PDGF)-induced increase in Egr-1 mRNA and protein levels was inhibited by 75% and
      74%, respectively. At the same time Egr-1 antisense oligonucleotides dose
      dependently inhibited MC-proliferation as determined by thymidine-uptake by up to
      75%. Control oligonucleotides were without effects on Egr-1 mRNA, protein or MC
      growth. CONCLUSION: We conclude that Egr-1 induction is a necessary step in the
      mitogenic signaling cascade in glomerular MCs.

PMID- 9139214
TI  - [Cardiovascular risk factors in diabetic nephropathy].
AB  - BACKGROUND: Diabetic nephropathy is associated with increased cardiovascular
      mortality. This may be contributed to by changes in plasma lipids, fibrinogen and
      hemorheology. Cardiovascular autonomic dysfunction, which is related to an
      increased incidence of arrhythmic death, may also play a role. PATIENTS AND
      METHODS: Therefore, we investigated in 58 IDDM-patients with none (n = 28),
      incipient (albuminuria 30 to 300 mg/day, n = 11) and overt clinical nephropathy
      (albuminuria > 300 mg/day, n = 19) plasma concentrations of lipoproteins and
      fibrinogen, plasma viscosity, erythrocyte aggregation and erythrocyte rigidity.
      Assessments of neuropathy included tibial nerve motor conduction velocity,
      perception of vibration, beat-to-beat variation during rest and during forced
      respiration, heart-rate response to Valsalva maneuver and heart-rate response to
      standing (30:15). RESULTS: Patients with clinical overt nephropathy had, compared
      to those without nephropathy, significantly higher concentrations of LDL
      cholesterol, triglycerides and fibrinogen, significantly lower concentrations of
      HDL-cholesterol and significantly higher plasma viscosity, erythrocyte
      aggregability and erythrocyte rigidity. Regarding the assessments of neuropathy
      we found in patients with nephropathy, compared to those without nephropathy,
      significantly reduced tibial nerve motor conduction velocity, reduced perception
      of vibration thresholds and reduced heart rate variability during rest, during
      forced respiration, in response to Valsalva maneuver and in response to standing.
      In diabetic patients with microalbuminuria erythrocyte aggregability and
      erythrocyte rigidity were significantly higher and heart rate variability during
      rest was significantly lower than in patients without nephropathy. CONCLUSION: In
      clinical overt nephropathy there is an aggregation of different cardiovascular
      risk factors, namely, disturbances in lipoprotein concentrations, increased
      fibrinogen concentration and disturbances in hemorheology. Furthermore marked
      deterioration in peripheral and autonomic cardial nerve function in these
      patients is evident accounting for a part of the greatly increased cardiovascular
      mortality of these patients.

PMID- 9139215
TI  - [Indications for intravenous urography].

PMID- 9139216
TI  - [Oncology '96].

PMID- 9139217
TI  - Euthanasia and physician-assisted suicide in the Netherlands.

PMID- 9139218
TI  - Euthanasia and physician-assisted suicide in the Netherlands.

PMID- 9139219
TI  - Euthanasia and physician-assisted suicide in the Netherlands.

PMID- 9139220
TI  - Euthanasia and physician-assisted suicide in the Netherlands.

PMID- 9139221
TI  - Primary biliary cirrhosis.

PMID- 9139222
TI  - Primary biliary cirrhosis.

PMID- 9139223
TI  - Endometrial carcinoma.

PMID- 9139224
TI  - Endometrial carcinoma.

PMID- 9139225
TI  - Tamoxifen-induced endometrial polyp.

PMID- 9139226
TI  - Congenital hypothyroidism caused by mutations in the thyrotropin-receptor gene.

PMID- 9139227
TI  - gamma/delta T-cell lymphoma of the thyroid gland.

PMID- 9139228
TI  - Mother-to-infant transmission of HIV.

PMID- 9139229
TI  - Treatment of burns.

PMID- 9139230
TI  - Treatment of burns.

PMID- 9139231
TI  - Solution to "A medical mystery".

PMID- 9139232
TI  - Solution to "A medical mystery".

PMID- 9139233
TI  - Contributing mechanisms for cysteine excitotoxicity in cultured cerebellar
      granule cells.
AB  - Several possible mechanisms for cysteine toxicity on rat cerebellar granule cells
      were studied and compared with the excitotoxic effect of glutamate. It was shown
      that the excitotoxic potency of both cysteine and glutamate increased in the
      presence of elevated concentrations of bicarbonate or increased pH.
      Pharmacological studies showed that the cysteine toxicity was specifically
      coupled to the NMDA receptor, whereas the glutamate toxicity was mediated to a
      smaller extent also by non-NMDA receptors. Treatment of cerebellar granule cells
      with cysteine led to an increased extracellular level of glutamate. In addition,
      cysteine sensitized NMDA receptors by reducing disulfide bonds in the receptor to
      sulfhydryl groups. A mechanism for cysteine excitotoxicity may therefore be
      formation of cysteine-sensitized NMDA receptors that are stimulated either by
      cysteine and/or by endogenous glutamate. This mechanism may also be important for
      the effects observed during regulated physiological release of cysteine.

PMID- 9139234
TI  - Sensitivity of ATPase-ADPase activities from synaptic plasma membranes of rat
      forebrain to lipid peroxidation in vitro and the protective effect of vitamin E.
AB  - The in vitro effects of membrane lipid peroxidation on ATPase-ADPase activities
      in synaptic plasma membranes from rat forebrain were investigated. Treatment of
      synaptic plasma membranes with an oxidant generating system
      (H(2)0(2)/Fe(2+)/ascorbate) resulted in lipid peroxidation and inhibition of the
      enzyme activity. Besides, trolox as a water soluble vitamin E analogue totally
      prevented lipid peroxidation and the inhibition of enzyme activity. These results
      demonstrate the susceptibility of ATPase-ADPase activities of synaptic plasma
      membranes to free radicals and suggest that the protective effect against lipid
      peroxidation by trolox prevents the inhibition of enzyme activity. Thus,
      inhibition of ATPase-ADPase activities of synaptic plasma membranes in cerebral
      oxidative stress probably is related to lipid peroxidation in the brain.

PMID- 9139235
TI  - Ethanol potentiates the uptake of [14C]serine into phosphatidylserine by base
      exchange reaction in NG 108-15 cells.
AB  - Phospholipid base-exchange enzymes catalyze the incorporation of nitrogenous
      bases into phosphoglycerides by a calcium-dependent mechanism. In this study, we
      describe the effect of ethanol on the incorporation of radioactive serine,
      choline and ethanolamine into their respective phospholipids in a neuroblastoma x
      glioma hybrid cell line (NG 108-15). Long term ethanol exposure induced a
      potentiation of the incorporation of [14C]serine into phosphatidylserine.
      Moreover, the phosphorus content of PS was found to be increased after long-term
      ethanol exposure. No concomitant changes in the phosphorus content of other
      phospholipids were observed. The results indicate that in NG 108-15 cells, the
      incorporation of radiolabelled serine into PS is potentiated during chronic
      ethanol exposure.

PMID- 9139237
TI  - On the significance of perfusion rate in the study of glutamate release from
      superfused synaptosomes.
AB  - The effect of perfusion rate on the apparent release of [(3)H]glutamate from
      prelabelled and superfused rat cortical synaptosomes was examined. The proportion
      of tissue [(3)H]glutamate released in response to a 4 ml depolarizing pulse of 15
      mM K+ increased almost linearly with perfusion rates from 1 ml min(-1) to 10 ml
      min(-1). Release did not increase markedly between 10 ml min(-1) and 20 ml min(
      1). The basal efflux of [(3)H]glutamate also increased with perfusion rate. The
      increase in both basal efflux and (K+)-induced release is interpreted as being
      due to a greater amount of released transmitter avoiding recapture by uptake
      processes as perfusion rate increases. This is supported by the observation that
      increasing the potential number of uptake sites in the tissue decreases both the
      basal and (K+)-evoked release of the transmitter. The significance of this with
      respect to optimal perfusion rates for studies on the regulation of glutamate
      release is discussed.

PMID- 9139236
TI  - Development of glial cells cultured from prenatally alcohol treated rat brain:
      effect of supplementation of the maternal alcohol diet with a grape extract.
AB  - The aim of this work was to investigate the effect of supplementation of a
      maternal alcohol diet with a grape extract on glial cell development. Glial cells
      were cultured during 4 weeks from cortical brain cells of the new born offspring
      in DMEM medium supplemented with fetal calf serum. Enzymatic markers of nerve
      cell development were measured (enolase isoenzymes and glutamine synthetase).
      Since alcohol consumption produces free radicals the antioxidant system
      superoxide dismutase was also investigated. Compared to the decrease found in
      only alcohol treated animals, all parameters except neuron-specific enolase were
      antagonized and even stimulated after grape extract supplementation. The effect
      was more important after only 1 month than 3 months of treatment. Also in the
      total brain an alcohol antagonizing effect and a glutamine synthetase activation
      were found. Our data demonstrate that addition of a grape extract to the maternal
      alcohol diet may partially or completely overcome the alcohol induced retardation
      of glial cell development.

PMID- 9139238
TI  - Differential responsiveness of metabotropic glutamate receptors coupled to
      phosphoinositide hydrolysis to agonists in various brain areas of the adult rat.
AB  - The effects of metabotropic glutamate receptor (mGluR) agonists on inositol
      phosphates (IP) accumulation were investigated in slices of the cerebral cortex,
      hippocampus, striatum and cerebellum of adult Sprague-Dawley rats. EC(50) values
      for 1S, 3R-1-aminocyclopentane-1, 3-dicarboxylic acid (ACPD) did not differ
      significantly between various brain areas (range 10(-5) M), quisqualate was the
      most potent in all the brain areas (range 10(-7) - 10(-6) M), except the
      cerebellum (10(-5) M), ibotenate was the most potent in the striatum (range 10(
      6) M) and the least potent in the cerebral cortex and hippocampus (range 10(-4)
      M). The efficacy in the four brain areas showed the following trend of ranking
      order for ACPD and quisqualate: hippocampus > striatum > cerebral cortex >
      cerebellum, and for ibotenate: hippocampus > cerebral cortex > striatum >
      cerebellum, although the observed differences reached the level of statistical
      significance only in the case of ACPD (hippocampus and striatum vs cerebellum)
      and ibotenate (hippocampus vs cerebellum). Co-incubation of the agonists at
      maximally effective concentrations in any pairwise combination resulted in no
      substantial additivity of IP accumulation. D,L-1-amino-3-phosphonopropionic acid
      (AP3) and D,L-2-amino-4-phosphonobutyric acid (AP4) at 0.5 mM concentration
      antagonized ACPD-induced IP accumulation by about 70 and 45 percent,
      respectively, without differences between brain areas. On the other hand, the
      antagonistic effects of L-serine-o-phosphate (SOP) at 1 mM concentration were the
      highest in the hippocampus (75 percent) and the lowest in the cerebellum (25
      percent). The comparative data indicate considerable regional receptor
      heterogeneity, in terms of different ratios of response to the agonists (but not
      antagonists, except SOP). There is a robust responsiveness of mGluRs not only in
      the hippocampus and cerebral cortex, but also in the striatum which exhibits the
      highest affinity to both quisqualate and ibotenate.

PMID- 9139239
TI  - Metrifonate induces cholinesterase inhibition exclusively via slow release of
      dichlorvos.
AB  - Metrifonate, a long-acting cholinesterase (ChE) inhibitor with very low toxicity
      in warm-blooded animals, inhibits rat brain and serum cholinesterase (ChE) in
      vitro through its hydrolytic degradation product, dichlorvos. This conclusion is
      based on the finding that metrifonate-induced ChE inhibition showed the same pH
      dependence as its reported dehydrochlorination to dichlorvos. The ChE inhibition
      induced by dichlorvos was not pH dependent. It was mediated by a competitive drug
      interaction with the catalytic site of the enzyme, which led to irreversible
      inhibition within several minutes of incubation. After this time, addition of
      further substrate to the inhibited enzyme was not able to promote drug
      dissociation and hence enzyme reactivation. Similar characteristics of
      inhibition, i.e. interaction with the substrate binding site and time-dependent
      switch to non-competitive inhibition were observed with the reference compound,
      physostigmine. However, the physostigmine-induced inhibition of ChE could be
      readily reversed by further substrate addition. Another reference compound,
      tetrahydroaminoacridine (THA), also induced a reversible inhibition of rat brain
      and serum cholinesterase, but with a mechanism of action different from that of
      both dichlorvos and physostigmine in that enzyme inhibition occurred rapidly upon
      drug addition at an allosteric site on the enzyme surface. It is suggested that
      the unique slow release plus the slow inhibition of ChE by dichlorvos is
      responsible for the lower toxicity of metrifonate compared to that of directly
      acting ChE inhibitors.

PMID- 9139240
TI  - Metrifonate and dichlorvos: effects of a single oral administration on
      cholinesterase activity in rat brain and blood.
AB  - Cholinesterase activities in rat forebrain, erythrocytes, and plasma were
      assessed after a single oral administration of metrifonate or dichlorvos. In 3
      month-old rats, the dichlorvos (10 mg/kg p.o.)induced inhibition of
      cholinesterase reached its peak in brain after l5-45 min and after 10-30 min in
      erythrocytes and plasma. Cholinesterase activity recovered rapidly after the peak
      of inhibition, but did not reach control values in brain and erythrocytes within
      24 h after drug administration. The recovery of plasma cholinesterase activity,
      in contrast, was already complete 12 h after dichlorvos treatment. Metrifonate
      (100 mg/kg p.o.) had qualitatively similar inhibition kinetics as dichlorvos,
      albeit with a slightly delayed onset. Peak values were attained 45-60 min (brain)
      and 20-45 min (blood), after drug administration. Apparently complete recovery of
      cholinesterase activity was noted in both tissues 24 h after treatment. The dose
      dependence of drug-induced inhibition of cholinesterase in rat blood and brain
      was determined at the time of maximal inhibition, i.e., 30 min after dichlorvos
      treatment and 45 min after metrifonate treatment. The oral ED(50) values obtained
      for dichlorvos were 8 mg/kg for brain and 6 mg/kg for both erythrocyte and plasma
      cholinesterase. The corresponding oral ED(50) values for metrifonate were 10 to
      15 times higher, i.e., 90 mg/kg in brain and 80 mg/kg in erythrocytes and plasma.
      In rats deprived of food for 18 h before drug treatment, the corresponding ED(50)
      values for metrifonate were 60 and 45 mg/kg, respectively, indicating an about
      two-fold higher sensitivity of fasted rats to metrifonate-induced cholinesterase
      inhibition compared to non-fasted rats. Compared to 3-month-old rats, 19-month
      old rats showed a higher sensitivity towards metrifonate and dichlorvos. At the
      time of maximal inhibition, there was a strong correlation between the degree of
      cholinesterase inhibition in brain and blood. These results demonstrate that
      single oral administration of metrifonate and dichlorvos induces an inhibition of
      blood and brain cholinesterase in the conscious rat in a dose-dependent and
      apparently fully reversible manner. While the efficiency of a given dose of
      inhibitor may vary with the satiety status or age of the animal, the extent of
      brain ChE inhibition can be estimated from the level of blood ChE activity.

PMID- 9139241
TI  - Effects of an inhibitor of adenosine deaminase, deoxycoformycin, and of
      nucleoside transport, propentofylline, on post-ischemic recovery of adenine
      nucleotides in rat brain.
AB  - The effects of an adenosine deaminase inhibitor (deoxycoformycin, 500 mu g/kg)
      and of an inhibitor of nucleoside transport (propentofylline, 10 mg/kg) on
      adenosine and adenine nucleotide levels in the ischemic rat brain were
      investigated. The brains of the rats were microwaved before, at the end of a 20
      min period of cerebral ischemia (4 vessel occlusion + hypotension), or after 5,
      10, 45, and 90 min of reperfusion. Deoxycoformycin increased brain adenosine
      levels during both ischemia and the initial phases of reperfusion. AMP levels
      were elevated during ischemia and after 5 min of reperfusion. ATP levels were
      elevated above those in the non-treated animals after 10 and 45 min of
      reperfusion. ADP levels were elevated above the non-drug controls at 90 min.
      These increases in ATP, ADP and AMP resulted in significant increases in total
      adenylates during ischemia, and after 10 min and 90 min of reperfusion.
      Propentofylline administration resulted in enhanced AMP levels during ischemia
      but did not alter adenosine or adenine nucleotide levels during reperfusion in
      comparison with non-treated controls.

PMID- 9139242
TI  - Regional distribution of binding sites for the nitric oxide synthase inhibitor L
      [3H]nitroarginine in rat brain.
AB  - The regional distribution of NG-nitro-L-[(3)H]arginine (L-[(3)H]NOARG) binding to
      different regions of rat brain was studied by quantitative autoradiography. These
      studies revealed highest density of binding sites in cerebellum, anterior
      olfactory nucleus, islands of Calleja and substantia nigra with appreciable
      binding site densities in inferior colliculus, superior colliculus, olfactory
      tubercle and dorsal tegmental nucleus. The regional distribution of L-[(3)H]NOARG
      binding, is in good agreement with the distribution of nitric oxide synthase
      studied previously by NADPH-diaphorase staining and immunohistochemistry using
      antibodies against neuronal nitric oxide synthase. The kinetics of L-[(3)H]NOARG
      binding to the cytosolic preparations of cerebral cortex, cerebellum, hippocampus
      and striatum was studied using an in vitro binding technique. Specific L
      [(3)H]NOARG binding was of nanomolar affinity, saturable, and best fit to a
      single-site model in all four brain regions. These studies support the potential
      use of L-[(3)H]NOARG binding as a tool for further elucidation of the regional
      distribution and functional properties of NOS in the central nervous system.

PMID- 9139243
TI  - Glutamate receptor agonists evoked Ca(2+)-dependent and Ca(2+)-independent
      release of [3H]D-aspartate from cultured chick retina cells.
AB  - We studied the release of [3H]D-aspartate evoked by glutamate receptor agonists
      from monolayer cultures of chick retina cells, and found that activation of the
      glutamate receptors can evoke both Ca(2+)-dependent and Ca(2+)-independent
      release of [3H]D-aspartate. In Ca(2+)-free (no added Ca2+) Na+ medium, the
      agonists of the glutamate receptors induced the release of [3H]D-aspartate with
      the following rank order of potency: kainate > alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) approximately N-methyl-D-aspartate (NMDA). In
      media containing 1 mM CaCl2 the release of [3H]D-aspartate evoked by NMDA,
      kainate and AMPA was increased by about 112 percent, 20 percent and 39 percent,
      respectively, as compared to the release evoked by the same agonists in Ca(2+)
      free medium. NMDA was the most potent agonist in stimulating the Ca(2+)-dependent
      release of [3H]D-aspartate, possibly by exocytosis, and AMPA was as potent as
      kainate. The Ca(2+)-dependent release of [3H]D-aspartate evoked by kainate was
      dependent on the influx of Ca2+ through the receptor associated channel, as well
      as through the N-(omega-Conotoxin GVIA-sensitive) and L- (nitrendipine-sensitive)
      type voltage-sensitive Ca2+ channels (VSCC). The exocytotic release of [3H]D
      aspartate evoked by AMPA relied exclusively on Ca2+ entry through the L-type
      VSCC, whereas the effect of NMDA was partially mediated by the influx of Ca2+
      through the receptor-associated channel, but not through L- or N-type VSCC. Thus,
      activation of these different glutamate receptors under physiological conditions
      is expected to cause the release of cytosolic and vesicular glutamate, and the
      routes of Ca2+ entry modulating vesicular release may be selectively recruited.

PMID- 9139244
TI  - Demonstration and characterization of hippocampal cholinergic neurostimulating
      peptide (HCNP) processing enzyme activity in rat hippocampus.
AB  - Hippocampal cholinergic neurostimulating peptide (HCNP) stimulates cholinergic
      activity of cultured medial septal nuclei explants. It consists of eleven amino
      acids that are located at the N-terminal region of its precursor protein. This
      report concerns the demonstration and characterization of an HCNP processing
      enzyme that cleaves the bioactive undecapeptide from the precursor. The enzyme
      was purified from the hippocampus of young Wistar rats. A synthetic deacetylated
      peptide (peptide(1-26)) consisting of the N-terminal 26 amino acids of the HCNP
      precursor protein served as substrate. The product of the enzyme reaction was
      identified and quantitated by HPLC using deacetylated HCNP as standard. The
      amount of undecapeptide generated was directly proportional to the time of
      incubation of the enzyme reaction mixture. From molecular sieving chromatography
      it was estimated that the molecular mass of the enzyme is close to 68 kDa. The
      HCNP processing enzyme has a pH optimum of 6.0 and a K m of 0.50 mM for peptide(1
      26). Preincubation at 56 degrees C causes rapid inactivation of the HCNP
      processing activity. Enzyme activity is enhanced by EDTA and 1,4-dithiothreitol,
      and inhibited by antipain, chymostatin and E-64. These findings suggest that the
      enzyme probably has a thiol group in its active site. This novel enzyme of the
      hippocampus may represent a valuable tool for further studies on the general
      protein metabolism in the central nervous system, as well as for elucidating the
      neurochemical aspects of neurodegenerative disorders.

PMID- 9139246
TI  - [Cells of the neural crest and their derivatives in vertebrates: the mechanisms
      of migration and its role in tissue formation].
AB  - Segregation, determination and migration of the neural crest cells have been
      considered in the head and trunk of birds and mammals, with special reference to
      segment-specific migration. The mechanisms of their migration and involvement in
      formation of some organs are discussed, as well as the model of "catch" of the
      neural crest cells proposed for explanation of the morphogenetic processes.

PMID- 9139247
TI  - [The role of homeobox cluster genes in animal morphogenesis].
AB  - A review of the published data on function of the cluster homeobox genes in
      embryogenesis of Drosophila and higher vertebrates. The role of these genes has
      been considered as concerns formation of the positional information in the body
      of the embryo and its organs. This system of genes appears to be universal in
      animals with various developmental pathways.

PMID- 9139245
TI  - Genes encoding giant danio and golden shiner ependymin.
AB  - Ependymin (EPN) is a brain glycoprotein that functions as a neurotrophic factor
      in optic nerve regeneration and long-term memory consolidation in goldfish. To
      date, true epn genes have been characterized in one order of teleost fish,
      Cypriniformes. In the study presented here, polymerase chain reactions were used
      to analyze the complete epn genes, gd (1480 bp), and sh (2071 bp), from
      Cypriniformes giant danio and shiner, respectively. Southern hybridizations
      demonstrated the existence of one copy of each gene per corresponding haploid
      genome. Each gene was found to contain six exons and five introns. Gene gd
      encodes a predicted 218-amino acid (aa) protein GD 93 percent conserved to
      goldfish EPN, while sh encodes a predicted 214-aa protein SH 91 percent
      homologous to goldfish. Evidence is presented classifying proteins previously
      termed "EPNs" into two major categories: true EPNs and non-EPN cerebrospinal
      fluid glycoproteins. Proteins GD and SH contain all the hallmark, features of
      true EPNs.

PMID- 9139248
TI  - [The characteristics of the prenatal morphogenesis of human lungs in the area of
      the action of the radiation factors after the accident at the Chernobyl Atomic
      Electric Power Station].
AB  - The effects of irradiation at low doses on prenatal development were studied
      using the abortion materials from the controlled zones of Bryansk Province,
      Russia. A possibility of transplacental transition of some radionuclides (90Sr
      and 137Cs) was shown, as well as appearance of their traces in tissues of some
      fetuses starting from the second trimester of pregnancy. The presence of
      radionuclides in the muscle and bones was combined in some cases with teratogenic
      effects, including lung hypoplasia. Reliable delay of the bronchi branching
      according to the morphometry of lung histological sections was found in the
      offspring of irradiated mothers during the first trimester of pregnancy, thus
      suggesting disturbed prenatal morphogenesis of the lungs. Lung hypoplasia was
      sometimes noted during the second and third trimesters of pregnancy. The lymphoid
      cells of the lungs in fetuses were activated and a trend was found to enhanced
      extravascular local erythroid hemopoiesis. This is considered by the authors as
      compensatory-adaptive cellular reactions in the respiratory organs to tissue
      hypoxia and antigenic stimuli from the irradiated maternal organism.

PMID- 9139249
TI  - [Screening for microalbuminuria in diabetic patients in the primary health care
      system].
AB  - In order to detect the prevalence of microalbuminuria, a screening procedure was
      carried out in 1016 adult (age > 14 years) diabetic patients registered in
      primary health care system at the 17st district of the capital. The clinical
      characteristics of patients were investigated and microalbuminuria was measured
      by immunoturbidimetric method using first void morning urinary samples. In this
      way, the urinary albumin/creatinine ratio was calculated (abnormal value in men >
      or = 2.5 mg/mmol, in women > or = 3.5 mg/mmol). Moreover, serum creatinine, blood
      glucose, serum cholesterol and triglycerides were measured in fasting blood
      samples. After applying exclusion criteria data of 933 diabetic patients [129
      insulin-dependent (IDDM) and 804 non-insulin-dependent (NIDDM) patients; 424 men,
      509 women] were analysed. Abnormal urinary albumin/creatinine ratio was found in
      315 (33.8%) patients. Microalbuminuria was detected in 32 (24.8%) IDDM and in 201
      (25.0%) NIDDM patients. Macroalbuminuria was found in 13 (10.1%) IDDM and in 69
      (8.6%) NIDDM patients. Abnormal urinary albumin/creatinine ratio was more often
      found in men than in women (IDDM men 41.3%, IDDM women 28.8%; NIDDM men 38.0%,
      NIDDM women 30.0%). Significant difference was found between diabetic patients
      with (n = 315) and without (n = 618) abnormal urinary albumin/creatinine ratio
      regarding age (64.3 +/- 0.7 years vs. 61.4 +/- 0.5 years; p < 0.001), duration of
      diabetes (10.3 +/- 0.5 years vs 7.9 +/- 0.3 years; p < 0.001) systolic blood
      pressure (151 +/- 1 mmHg vs 146 +/- 1 mmHg; p < 0.01), serum creatinine (99 +/- 2
      mumol/l vs 88 +/- 1 mumol/l; p < 0.001) and blood glucose (10.4 +/- 0.2 mmol/l vs
      9.4 +/- 0.1 mmol/l; p < 0.001). One third (33.8%) of diabetic patients in primary
      health care setting exhibited signs or were at risk of renal involvement of
      diabetes. Diabetic patients with micro- or macroalbuminuria should be carefully
      controlled in order to prevent or to decrease deterioration of renal function due
      to diabetic nephropathy.

PMID- 9139250
TI  - [Thrombocyte dysfunction in children with albinism].
AB  - Seven children with albinism were examined for haemorrhagic diathesis. In 6
      patients coagulation screening tests (prothrombin time, activated partial
      thromboplastin time, thrombin time) were normal, in 1 patient prolongation of
      activated partial thromboplastin time due to mild factor XI deficiency was found.
      Platelet counts were in the reference range, however, the template bleeding time
      of 6 out of 7 patients was prolonged. Evaluation of platelet aggregation and
      secretion in a lumi-aggregometer demonstrated that only the child with normal
      bleeding time had normal platelet function, and 6 children with prolonged
      bleeding time had impaired aggregation and release reaction. Five out of these 6
      patients had severe decrease of ATP secretion even when high dose of thrombin was
      used as agonist. The number of dens granules in the platelets of these patients,
      as measured by the uptake of mepacrine, was significantly less than in normal
      controls. These findings clearly suggested storage pool deficiency. In one of
      these patients storage pool deficiency was associated with mild factor XI
      deficiency. The high frequency of haemorrhagic diathesis in albino children
      emphasizes, the importance of the screening of patients with albinism for
      bleeding diathesis.

PMID- 9139251
TI  - [Simple parameters of antibiotic utilization and diagnostic background of
      antimicrobial therapy in Hungarian hospitals in 1995].
AB  - This paper is published as second part of a survey on antibiotic utilisation of 8
      Hungarian hospitals in January, 1995. The length of hospital stay of the patients
      receiving systemic antibiotic treatment was significantly higher (P < 0.0001)
      than those of not receiving such treatment. After exclusion of the patients
      suffering from nosocomial infections, average of the excess of hospital days was
      4.65. Comparing the figures of patients receiving one or more antibiotic/one
      hospital stay and the rate of monotherapy and combined therapy and number of used
      antibiotics/100 discharged patients or/100 patients treated with antibiotics it
      was found that these indexes were most favourable in that hospital, where
      antibiotic policy was in function. Examining diagnoses (perioperative profilaxis
      32.7%, pneumonia 13.3% of the 753 diagnoses) and drugs (metronidazol 26.3%,
      aminoglycosides 20% of the 1455 antibiotics) most frequently found in cases of
      combined antibiotic therapy it was concluded that parallel treatment with two or
      more antibiotic was often unjustified. Only 11% of antibiotics was used as
      directed against known bacteria. It was found that the rate of the achieved
      microbiological examinations and targeted therapy was low even if microbiological
      samples were easy to obtain. It was not the main purpose of the survey to get
      data of the clinical diagnostic background of antibiotic therapy, but indirect
      signs showed that these drugs were often used without sufficient clinical
      evidences (anamnesis, physical status, labor, X-ray and other tests) of
      infection. Authors recommend further survey in order to find out the causes of
      insufficiency of diagnoses. They also propose elaboration of diagnostic
      protocols.

PMID- 9139252
TI  - [Laparoscopic cholecystectomy in patients with liver cirrhosis].
AB  - Between 01. January 1994 and 31. December 1995 during 552 laparoscopic
      cholecystectomy the authors observed moderate or severe liver cirrhosis in 27
      patients. They performed successful operations on all of the 27 patients with two
      conversions. None of the patients died. They discuss complications of the
      operations performed in liver cirrhosis, and state, that the existence of the
      cirrhosis does not contraindicate the laparoscopic cholecystectomy, moreover in
      the hands of a surgeon with great laparoscopic experience this method is more
      indulgent and has less complications than cholecystectomy performed with
      traditional methods.

PMID- 9139254
TI  - [Modifying data on an old debate (Ignacz Semmelweiss)].

PMID- 9139253
TI  - [Prenatal diagnosis of fetal thrombocytopenia].
AB  - A case of maternal idiopathic thrombocytopenic purpura complicated by severe
      fetal thrombocytopenia is reported. Fetal thrombocytopenia was diagnosed by scalp
      blood-sampling during labour. With discussion of the relevant literature, the
      authors recommend the use of their method in thrombocytopenic patients in labour.
      In cases of fetal thrombocytopenia Caesarean section in recommended to prevent
      trauma and subsequent neonatal haemorrhagic complications.

PMID- 9139255
TI  - [An old book about child health].

PMID- 9139256
TI  - Laryngeal carcinoma nodal metastases and their management.
AB  - Each of the three embryologically distinct portions of the larynx has a
      characteristic lymphatic drainage pattern. One section of this article describes
      these drainage patterns, along with clinical examples. Traditional and
      contemporary imaging techniques for the neck are included in a second section,
      and the final section describes the authors' preferences for treatment of the
      neck with the rationale for this approach.

PMID- 9139257
TI  - Variation in the nature of attachment of phosphorylcholine to excretory-secretory
      products of adult Brugia pahangi.
AB  - The mechanism of linkage of phosphorylcholine (PC) to excretory-secretory
      products (ES) of adult Brugia pahangi has been investigated. Biosynthetic radio
      isotope labelling of ES with [3H]choline followed by SDS-PAGE/fluorography
      revealed a smear of molecular weight approximately 40-100 kDa which loses its
      radiolabel following exposure to N-glycosidase F, but not mild alkali. PC is thus
      attached to this smear of molecules via N-type glycans, a mechanism of linkage
      previously observed with respect to PC-ES of Acanthocheilonema viteae. Western
      blotting analysis of non-radiolabelled ES demonstrated the existence of
      additional PC-ES which were insensitive to N-glycosidase F, but not to alkali.
      This second group of molecules is therefore likely to contain PC linked to O
      glycans. Filarial nematodes may thus utilize 2 classes of glycan for attachment
      of PC. Examination of B. pahangi and A. viteae whole worm extracts by Western
      blotting indicated that their PC content could not be cleaved by N-glycosidase F
      and hence the use of N-type glycans may be restricted to a subset of ES products.
      The implications of these findings with respect to developing inhibitors of PC
      attachment for use as anti-filarial drugs are discussed.

PMID- 9139258
TI  - A survey of knowledge, attitude, and practice of cervical screening among
      Lebanese/Armenian women.

PMID- 9139259
TI  - Looking beyond primary care to primary health care: an approach to community
      based action.

PMID- 9139260
TI  - Ethical issues relative to autonomy and personal control in independent and
      cognitively impaired elders.

PMID- 9139261
TI  - Ethnic diversity and staff nurse employment in hospitals.

PMID- 9139262
TI  - Immigrant transitions and health care: an action plan.

PMID- 9139263
TI  - NINR and the nursing research community: the next 10 years ... the next century.

PMID- 9139264
TI  - Advocacy for health research means advocacy for patient care.

PMID- 9139265
TI  - What is happening?

PMID- 9139266
TI  - Women's health and women's health care: recommendations of the 1996 AAN Expert
      Panel on Women's Health.

PMID- 9139267
TI  - Persistent Carer. Interview by Jo Carlowe.

PMID- 9139269
TI  - Culture vulture. Interview by Janet Snell.

PMID- 9139268
TI  - High Seas, high drama.

PMID- 9139270
TI  - [Use of hematopoietic stem cells in gene therapy].

PMID- 9139271
TI  - [The influence of heart infarction on the concentration of aminoterminal type III
      procollagen peptide in blood serum].
AB  - The reconstructive processes in a heart infarction pertain also the fibrous
      tissue sceleton, of which the main element are collagen fibres. The aim of the
      study was determination of variability of a specific collagen synthesis marker,
      i.e. the serum aminoterminal type III procollagen peptide (PIIINP) and its
      correlation with hydroxyproline (HP), hydroxylysin (HL) concentration as well as
      activity of creatine kinase (CK) and aspartate aminotransferase (AspAT) in serum
      after heart infarction. The investigations were carried out in 30 patients with a
      heart infarction with Q wave (group I), in 20 subjects with a heart infarction
      without Q wave (group II) and in 30 healthy subjects, comprising the C group. All
      these parameters were determined on the 1st, 2nd, 3rd, 5th and 10th day after
      onset of infarction. In comparison to the C group, in group I on the 1st day the
      PIIINP concentration was 3-fold higher and in group II it 2 1/2-fold higher (C =
      4.3 +/- 1.8; I = 14.2 +/- 3.9; II = 10.4 +/- 2.0 micrograms/l; p < 0.001). In
      group I even on the 10th day the concentration did not return to normal values,
      instead in group II it reached the values x + SD in C group after 5 days. There
      was no significant correlation between concentration of PIIINP and all other
      examined parameters stated. Heart infarction with a Q wave caused a relatively
      highest (% of mean values in C group) increase in CK and AspAT activity, PIIINP
      held a medial position, while HP and HL the lowest. After infarction without a Q
      wave the relative elevation of PIIINP concentration was near to the AspAT and HP
      increase. CONCLUSIONS: 1. the differences of serum PIIINP concentration are
      probably resulted by the magnitude of heart infarction. 2. During 10 days after
      the onset of heart infarction the serum concentration of PIIINP does not show any
      correlation with HP, HL and enzymatic heart infarct markers. 3. The results
      indirectly show, that the scar formation after heart infarction begins already on
      the first day.

PMID- 9139272
TI  - [Effect of heart infarction on levels of type I procollagen carboxyterminal
      peptide in blood serum].
AB  - The aim of the study was determination of the influence of heart infarction on
      the blood serum level of type I procollagen carboxyterminal peptide (PICP) and
      its covariability with concentration of hydroxyproline (HP) and hydroxylysine
      (HL) as well as activity of creatine kinase (CK) and aspartate transferase
      (AspAT). The investigations were carried out in 30 patients with a heart
      infarction with Q wave (group I) and in 20 subjects with a heart infarction
      without Q wave. The control group comprised 30 healthy subjects. The
      determination of all parameters was performed on the 1st, 2nd, 3rd, 5th and 10th
      day after the infarct onset. On the 1st day of heart infarction, the
      concentration of PICP in serum was (x +/- SD): gr. I-235 +/- 33, gr. II-209 +/-
      8, gr. C-65 +/- 17 micrograms/l. There was no co-variability of PICP
      concentration and the values of all other determined parametres. The authors
      conclude: 1. the increase of serum PICP concentration is connected probably with
      the magnitude of heart infarction, 2. the reconstruction process of the heart
      fibrous tissue and scar formation begins already on the first day of infarction
      onset, 3. during 10 days after infarction onset the serum PICP concentration does
      not correlate with HP, HL as well as the enzymatic heart infarct indices, namely
      CK and AspAT.

PMID- 9139273
TI  - [Activity of angiotensin-converting enzyme in serum and its association with left
      ventricular mass and blood pressure level in patients with essential
      hypertension].
AB  - Renin-angiotensin-aldosterone system plays an important role in regulation of
      blood pressure and it is one of causative factors in left ventricular hypertrophy
      in patients with hypertension. The results of previous studies did not answer the
      question of the relation between elevated plasma angiotensin-converting enzyme
      (ACE) activity and presence of essential hypertension or left ventricular
      hypertrophy in hypertension. The aim of the present study was to compare plasma
      ACE activity in patients with hypertension and healthy subjects and to explore
      the relation between the level of blood pressure, left ventricular mass (LVM) and
      plasma ACE activity in patients with essential hypertension. The investigations
      were carried out in 21 patients with mild and 29 patients with moderate
      hypertension. Control group for the evaluation of plasma ACE activity was 28
      healthy subjects. Plasma ACE activity was determined by spectrophotometric
      method. LVM was calculated on the basis of echocardiographic examination and was
      indexed to height (LVM/HT) and to body surface area (LVM/BSA). No significant
      differences in plasma ACE activity between patients with mild and moderate
      hypertension and healthy subjects were found out. Groups of patients with and
      without left ventricular hypertrophy did not differ significantly in plasma ACE
      activity. We did not find any relation between plasma ACE activity and left
      ventricular mass indexes as well as between plasma ACE activity and the level of
      systolic and diastolic blood pressure.

PMID- 9139274
TI  - [Increased urinary excretion of transforming growth factor beta and interleukin-6
      in patients with diabetic nephropathy].
AB  - The purpose of the study was to assess TGF-beta and IL-6 urinary excretion
      (measured with EIA) in 12 IDDM patients (7 F, 5 M, age 20-49 yrs, mean = 33.08)
      with albuminuria or microalbuminuria. Control group consists of 27 IDDM patients
      (12 F, 15 M, age 24-59 yrs. mean = 39.5) without albuminuria or microalbuminuria.
      Urinary excretion of IL-6 was significantly higher (p < 0.05) in IDDM patients
      with albuminuria (mean = 7.43 +/- 8.29 pg/mg creatinine) than in control group
      (mean = 3.74 +/- 2.64 pg/mg creatinine). Urinary excretion of TGF-beta was also
      higher (but not significantly in IDDM patients with albuminuria or
      microalbuminuria (mean = 42.0 +/- 30.0 pg/mg creatinine) than in control group
      (mean = 27.0 +/- 20.0 pg/mg creatinine). The data indicate that IL-6 and TGF-beta
      could be involved in the development of diabetic nephropathy.

PMID- 9139275
TI  - [Prognostic significance of doppler-derived and left ventricular diastolic
      filling variables in patients with dilated cardiomyopathy].
AB  - The purpose of this echocardiographic study was to evaluate the frequency of
      restrictive left ventricular filling pattern in dilated cardiomyopathy, as well
      as its clinical and echocardiographic correlations and prognostic implications.
      The study included 49 pts (39 males, 10 females) aged 32 to 56 years (mean age:
      46 years), with a diagnosis of dilated cardiomyopathy, according to the World
      Health Organization criteria. Pulsed Doppler echocardiographic analysis was
      performed at discharge and during a two year follow-up and compared with clinical
      and 2-dimensional echocardiographic findings. The patients were divided into two
      groups according to measurement of E decelaration time (DT) of transmitral flow
      patterns: a restrictive group (Group A-21 pts) with DT < 115 ms. and a non
      restrictive group (Group B-28 pts) with DT > 115 ms. Of 49 pts, 15 died during a
      two-year follow-up, 12 in the restrictive group and only 3 in the non-restrictive
      group. Eleven of these pts (73%) died of worsening of congestive heart failure
      and four (27%) died suddenly. The restrictive filling pattern was associated at
      Doppler study with a higher E wave velocity, lower A wave velocity and higher E/A
      ratio. Pts in the restrictive group were in a higher New York Heart Association
      functional class, and had a lower ejection fraction and more severe mitral
      regurgitation. In addition, they had a significantly larger right ventricle and
      higher mean pulmonary artery pressure. Mortality rate in the restrictive group
      was markedly higher than that in the non-restrictive group at 1 year (24% vs. 0%,
      respectively, p < 0.001) and at 2 years (57% vs. 11%, respectively, p < 0.001).
      The results from this study indicate that a restrictive left ventricular filling
      pattern is frequent in dilated cardiomyopathy, and is associated with more severe
      disease and is the single best clinical predictor for cardiac death in pts with
      dilated cardiomyopathy.

PMID- 9139276
TI  - [Long-term follow up of acute and chronic pancreatitis during insulin and peptide
      C secretion and carbohydrate tolerance].
AB  - The aim of the study was to evaluate the function of pancreatic the B-cell and
      carbohydrate tolerance after and during pancreatitis. Forty patients (30 men and
      10 women) in mean age 41.6 +/- 11.6 years (mean +/- SD) were studied. Analysis of
      the results was performed in four groups: 1) normal controls, 2) patients after
      biliary acute pancreatitis (AP) in anamnesis, 3) patients with chronic
      pancreatitis (ChP) and normal carbohydrate tolerance and 4) patients with chronic
      pancreatitis and impaired of glucose tolerance (ChP + IGT, WHO classification).
      Pancreatitic B-cell activity was evaluated by the measurement insulin (IRI) and C
      peptide (CP) serum concentrations in fasting state and after 75 g oral glucose
      and after intravenous glucagon injection (1 mg). Hepatic insulin extraction was
      estimated from of the serum IRI/CP molar ratio. This study demonstrated impaired
      function of the pancreatic B-cell in groups after acute pancreatitis and with
      chronic pancreatitis at normal levels of glycaemia. A progressive reduction of
      stimulated serum IRI and CP concentrations in groups (2), (3) and (4) was
      observed. In those groups the increase of serum IRI/CP ratio was found.
      CONCLUSIONS: Impaired function of the B-cell after pancreatitis is a frequent
      complication and to improve metabolic control a mechanism of hepatic insulin
      clearance reduction is involved.

PMID- 9139278
TI  - [An unusual case of Kartagener's syndrome associated with rheumatoid arthritis].
AB  - We observed a 56-year-old woman with Kartagener's syndrome and severe
      seropositive rheumatoid arthritis. This is the third case of such association in
      the world literature and a second one being diagnosed in our Department. The
      patient was also as the previous one a carrier of HLA DR1 and B27 antigens. An
      electromicroscopic study showed normal bronchial cilia in contrast to classical
      course of the disease. A number of immunological disturbances were observed,
      especially defective granulocyte function. We suggest that the severe course of
      rheumatoid arthritis may be related to the chronic stimulation of immune system
      by microbes continuously present in the patients airways.

PMID- 9139277
TI  - [Clinical characteristics of patients with hypertension resistant to
      antihypertensive drug therapy].
AB  - Two groups of hypertensive patients: 137 responsive (on one or two drugs) and 162
      resistant on antihypertensive treatment in the similar age were compared.
      Resistant patients (on three or more drugs) characterize by significantly higher
      body weight and BMI, longer history of hypertension, more frequent hypertension
      prevalance in family members and lower education. Level of triglycerides in
      resistant on antihypertensive treatment patients was significantly higher than in
      responsive patients. Insulin level in blood in 31 patients with essential
      hypertension was significantly higher than in 36 healthy persons and 20 patients
      with renovascular hypertension and resistant on antihypertensive therapy. In 14
      patients with essential hypertension resistant to treatment insulin level one
      hour after oral glucose load was significantly (p < 0.01) higher than in 16
      patients with essential hypertension responsive to antihypertensive treatment.

PMID- 9139279
TI  - [The role of endothelin in the physiology and pathophysiology of the circulatory
      system and kidneys].

PMID- 9139280
TI  - [Biliary microlithiasis and its association with acute idiopathic pancreatitis].

PMID- 9139282
TI  - [Professor Edward Szczeklik--life and achievements of an honorary member of the
      Polish Society of Internal Medicine].

PMID- 9139281
TI  - [Kearns-Sayre syndrome: encephalomyopathy caused by deletion of mitochondrial
      DNA].

PMID- 9139283
TI  - Geriatric psychiatry. What's new about the old. Introduction.

PMID- 9139284
TI  - Late-life psychiatric diagnosis in DSM-IV.
AB  - Age is an important variable in the consideration of psychiatric diagnosis. This
      applies particularly to the presentation of psychiatric disorders in late life.
      DSM-IV has made a start but much more could be done, particularly for some
      disorders. It is hoped that more attention to age, especially late life, will be
      paid in DSM-V and beyond.

PMID- 9139285
TI  - Depression in the elderly. Myths and misconceptions.
AB  - Despite myths to the contrary, existing evidence suggests that depression in the
      elderly is not different in its symptoms, more frequent, more chronic, more
      difficult to treat, or more attributable to psychosocial factors than depression
      in younger persons. The degree to which the pessimism generated by the untruths
      has overshadowed the realities uncovered by careful scientific inquiry is a
      disservice to older adults experiencing late-life depression.

PMID- 9139287
TI  - Anxiety disorders and insomnia in geriatric patients.
AB  - Anxiety and insomnia are among the more frequently encountered problems in
      geriatric cases. The effective clinical approach identifies underlying diagnostic
      syndromes or general medical conditions. An integrated approach to management
      combines pharmacotherapy and behavioral interventions as appropriate. Overall the
      prognosis for most patients is excellent.

PMID- 9139286
TI  - Bipolar mood disorders in the elderly.
AB  - Age effects on early-onset bipolar illness may include changes in affective
      features and recovery. Age effects on the pharmacokinetics of lithium are
      clinically relevant. Average age at onset is relatively late among geriatric
      bipolars. Late-onset bipolar disorder is associated with lower rate of familial
      illness than early-onset cases and greater medical and neurologic comorbidity.
      The limited literature available points to the need for further studies of
      geriatric bipolar disorder. In such investigation, the distinction between age
      and age at onset effects provides a framework within which to enhance knowledge
      of psychopathology, to expand understanding of natural history and the impact of
      therapeutic interventions, and to study mechanisms.

PMID- 9139288
TI  - The psychology of normal aging.
AB  - Health care providers need to be aware of the normal aspects of the aging process
      as well as exceptions that may necessitate clinical intervention. Although many
      exceptions exist, aging involves a heightened susceptibility or vulnerability to
      physiologic, psychological, and sociocultural insult. Sensory systems become less
      sensitive and acute, lifelong sleep patterns undergo change, and there is decline
      in certain aspects of memory. Longitudinal studies suggest, however, that the
      normal changes that occur in healthy older adults do not significantly impair
      cognitive functioning or interpersonal relationships. Grief resulting from loss
      is a normal part of life. It should not be "pathologized" nor should its impact
      be underestimated. Loss of a spouse, child, or other close loved one may
      negatively affect the immune system and other organ systems, and may disrupt the
      social support system. Although most grief reactions are resolved with the
      support of family or friends, grief can lead to depression, physical decline, or
      medically unexplained physical symptoms. Awareness of the normal aging processes
      enables the professional to be more effective in providing mental health
      services.

PMID- 9139289
TI  - Management of geriatric behavior problems.
AB  - Agitation has many causes, and we have no way of classifying it that dictates the
      choice of the right agents or methods of treatment. It is also difficult to judge
      the effectiveness of any method. Because agitation is an intermittent phenomenon
      one can seldom be certain if improvement or worsening is merely incidental to the
      form of treatment instituted. The complexity of behavior disturbances demands an
      approach that enlists the cooperation of all involved in the care of the patient,
      and the use of a broad range of remedies. With regard to prevention, we should
      help people anticipate infirmity and even dementia. If good health is not taken
      for granted, this encourages that the present be used more purposefully. More
      than ever before in history, it is important to plan for the last stages of life.
      A greater percentage of people can expect to live into the years of frailty than
      ever before. It may not seem like an attractive thing to do, but a periodic
      mental review of one's future may be prudent. The consequences of a lack of
      foresight are seen in too many elderly. A small dose of reality now can result in
      a better old age.

PMID- 9139290
TI  - Psychiatric presentations of medical illness.
AB  - Geriatric patients are subject to mental disorders that are due to the
      physiologic effects of medical illness or are substance induced. Elders are at
      increased risk for such syndromes because of the higher rates of physical
      illnesses and resultant polypharmacy as well as aging-related susceptibility to
      disruption of brain functioning. This article reviews psychiatric syndromes that
      are due to general medical conditions or are substance induced, focusing on the
      more common, acute conditions of delirium and psychotic, mood, and anxiety
      disorders that are due to general medical conditions. The ultimate goal of
      patient care must be accurate diagnosis with resultant optimal, appropriate
      treatment and improvement in functioning leading to the better well-being of the
      elderly patient.

PMID- 9139291
TI  - Pharmacodynamic and pharmacokinetic considerations in geriatric
      psychopharmacology.
AB  - Age-associated decreases in metabolism and elimination of drugs are sufficient to
      give one pause before prescribing drugs in the elderly particularly if multiple
      drugs are to be used. When one factors in concomitant drugs that may inhibit P450
      mediated metabolism of other more toxic drugs, genetic deficiency of P450
      enzymes, and medical illnesses such as liver and renal failure that will lead to
      further elevation of drug levels and delay in drug clearance, the likelihood of
      adverse events when multiple drugs are used in the elderly becomes truly
      dizzying. In consideration of the pharmacologic principles discussed, when
      prescribing drugs in the elderly, one might add to the often heard
      recommendation, "Start low and go slow," a third admonition, "Keep it as simple
      as possible!"

PMID- 9139292
TI  - Clinicoeconomics in geropsychiatry.
AB  - The question becomes, who will manage managed care and what will be used as a
      basis for rational decision making? It has been suggested that a policy
      regulating body composed of health care providers, payors, and patients be formed
      to oversee the process of health care reform and to discourage profit-driven
      managed care practices. It is particularly appealing to incorporate health care
      consumers into this process as representatives of evolving societal values. To
      make rational decisions, the proposed regulatory body will need data. In this
      regard the discipline of clinicoeconormics could provide information on the
      effectiveness and relative value of health care interventions. Geropsychiatrists
      must be willing to join the effort to learn about and participate in
      clinicoeconomics to shift the debate from the bottom line of a balance sheet to
      the preservation of quality care for the elderly and mentally ill.

PMID- 9139293
TI  - Geriatric psychiatry in primary care. A focus on ambulatory settings.
AB  - Considering how tightly interwoven are the strands of mental and physical health
      in the fabric of late life, it would be unwise for psychiatrists and primary care
      physicians to continue to insist on separately tracing and mending frayed old
      threads, each in mostly one direction, occasionally irritated by the shortcomings
      in the others work, and only occasionally seeking or offering assistance. As
      reflected in their help-seeking behavior and their characterization of suffering,
      the elderly often do not see, or do not choose to recognize, the theoretical and
      professional distinctions we hold so dear. Acknowledging the impact of the unmet
      needs of elderly patients, and respecting the wisdom of their choices, primary
      care physicians and psychiatrists have an obligation to work together more
      effectively. Improved mental health in our geriatric patients will require major
      efforts in the areas of research, public education, health care funding, and
      community resource development, as well as in individual patient care. Medical
      disciplines working in isolation or in opposition will not attenuate these
      obstacles effectively.

PMID- 9139294
TI  - Neuropsychological testing and assessment scales for dementia of the Alzheimer's
      type.
AB  - Neuropsychological assessment plays an important role in the process of
      diagnosing DAT. Whereas the brief screens are sensitive to the cognitive deficits
      associated with DAT, full battery measures should be used to rule out early
      dementia or to differentiate among the various dementing illnesses. Following
      diagnosis, there are numerous assessment measures that facilitate management and
      placement decisions. These measures include instruments that help stage the
      illness to determine severity, instruments that evaluate the patient's capacity
      to perform activities of daily living, and measures that evaluate for the
      behavior symptoms common in later-stage dementia.

PMID- 9139296
TI  - The genetics of dementia in late life.
AB  - Recent advances in the genetics of AD and other late-life dementias have provided
      new insights but also have raised new queries and ethical issues. This review
      reflects the current state of knowledge in a rapidly evolving field. The complex
      relation of genes and environment to AD, VaD, and other late-life dementias
      suggests that the answers to these many issues will evolve through time. New
      issues undoubtedly will arise as additional genes are discovered and new data
      accrue that relate APOE and other genes to the mechanism and expression of
      dementing illness. The clinical relevance and applicability of such research
      findings will increase when effective treatments become available. Given this
      potential, we encourage readers to monitor new developments as they arise.

PMID- 9139295
TI  - Differential diagnosis of dementia. The clinical process.
AB  - Dementia as a syndrome must be differentiated from nondementing conditions.
      Dementia itself must also be differentiated as to cause, as in certain cases
      reversible conditions may be responsible. This article examines the clinical
      process of such differentiation, providing a decision free for diagnosis and a
      summarizing algorithm for thinking through individual cases, with a focus on the
      most frequent cause of dementia, Alzheimer's disease. Also outlined are the
      stages of Alzheimer's disease, with the admonition that variations from the
      expected progression may represent a dementia diagnosis other than Alzheimer's
      disease or the co-occurrence of some other contributing factors.

PMID- 9139297
TI  - Current advances in Alzheimer's disease. A medical model paradigm for psychiatric
      education.
AB  - Psychiatrists have the expertise to play a major leadership role in the diagnosis
      and treatment of Alzheimer's disease. Psychiatry residents should be trained to
      recognize both the cognitive and noncognitive symptoms of this disease.
      Psychiatrists are in an excellent position to keep up with the rapidly expanding
      pharmacologic armamentarium to treat this devastating illness. Although such
      potentials are exciting, they undoubtedly will be complicated. Residency
      directors and departmental chairs should instill enthusiasm toward basic science
      advances and their clinical implications. Understanding the mechanisms underlying
      specific central nervous system illnesses should increase the likelihood of
      discovering the pathophysiology of others. The more psychiatrists and psychiatric
      residents become interested in these discoveries and the science underlying such
      progress in Alzheimer's disease, the better they will be able to keep up to date
      with progress in understanding other psychiatric disorders.

PMID- 9139298
TI  - Delirium in the elderly.
AB  - Delirium is a state of disturbed consciousness and attention and cognition or
      perception, which develops acutely, fluctuates during the course of the day, and
      is attributable to a physical disorder. This syndrome is the focus of increasing
      attention in light of emerging evidence of its enormous impact in human suffering
      as well as patient care costs. As currently conceptualized, delirium is a
      threshold phenomenon in which systemic and cerebral insults are cumulative and,
      in most cases, are multifactorial in origin. Because delirium results from an
      underlying medical condition, its prognosis is dependent largely on how quickly
      that condition is identified and appropriately treated. A basic algorithm for
      initial delirium management is reviewed, which includes discontinuing noncritical
      medications, instituting close observation, monitoring vital signs and fluid
      intake and output, obtaining a complete history, performing initial laboratory
      studies to determine the causes, implementing environmental and psychosocial
      interventions, and instituting pharmacologic treatment as indicated for agitation
      and psychosis. The pharmacologic treatment of choice is an antipsychotic of the
      butyrophenone class. Benzodiazepine use is reserved for the specific treatment of
      alcohol and sedative withdrawal, and for adjunctive use with antipsychotic agents
      in treatment-refractory cases. There is growing evidence that the cognitive
      impairment of delirium is not entirely reversible in all patients, and it may be
      that delirium represents a time of significant risk for progression of underlying
      dementia. Preventive measures discussed in the text are, therefore, of particular
      importance in this population.

PMID- 9139299
TI  - Cottonseed protein: what does the future hold?
AB  - Cottonseed protein has the potential to increase the world's food supply while
      decreasing the incidence of malnutrition among the world's hungry. Nutritionally,
      cottonseed flour compares favorably to other animal and vegetable protein
      sources, as it is low in fat and contains a substantial amount of high biological
      value protein. Animal studies, as well as human research, using gossypol-free
      glandless cottonseed flour have shown that cottonseed protein promotes growth,
      increased weight gain, and a positive nitrogen balance. Cottonseed protein food
      products have been shown to be a healthy addition to the diets of children,
      college-age women, and the elderly. With its light color and bland flavor,
      cottonseed has many uses in the food processing arena. Baked goods, snack foods
      and candy, as well as pet and livestock feed are just a few successful products
      developed utilizing cottonseed protein.

PMID- 9139300
TI  - Mineral content modifications during ripening of asparagus (Asparagus
      officinalis, L.).
AB  - The essential elements: calcium (Ca), magnesium (Mg), sodium (Na) potassium (K)
      and phosphorus (P) were analyzed in fresh asparagus to determine the effect of
      the ripening of the asparagus on the mineral content. Asparagus samples were
      classified in two groups by diameter (< 11 mm and > 14 mm). Asparagus from a
      sample group with the same diameter were divided into two portions (apical and
      basal) according to distance from the tip. The concentrations of calcium,
      magnesium and phosphorus increased with the ripening process of the asparagus
      while the content of sodium decreased when the white asparagus turned into a
      green ripening state. No significant differences were established for potassium.
      The green ripening state was the group with the greater concentration of calcium,
      magnesium and phosphorus. Statistically significant differences (p < 0.001) were
      observed between portions of asparagus (tip and rest of stem) in the contents of
      the five mineral elements analyzed. The levels of mineral elements investigated
      increased notably in the tip of the asparagus with the exception of sodium and
      potassium of which the levels in the apical portion decreased or hardly modified.
      The variance analyses determined statistically significant differences (p <
      0.001) in the concentration of magnesium, sodium and phosphorus between asparagus
      diameters (< 11 and > 14 mm) and no significant differences (p > 0.05) were found
      for calcium and potassium. The mean element levels were (mg/kg dry weight): Ca =
      324 +/- 1186; Mg = 1818 +/- 490; Na = 368 +/- 86; K = 37297 +/- 4167 and P = 6809
      +/- 2481.

PMID- 9139301
TI  - Nutrient composition and biological evaluation of mesta (Hibiscus sabdariffa)
      seeds.
AB  - Two varieties of mesta (Hibiscus sabdariffa) seeds were analysed for their
      proximal composition. Their protein (18.8-22.3%), fat (19.1-22.8%) and dietary
      fiber (39.5-42.6%) content were found to be high. The seeds were found to be a
      good source of minerals like phosphorus, magnesium and calcium. Their lysine and
      tryptophan contents were also high. Sulphur containing amino acids were limiting
      in this seed protein and the chemical score of mesta seed protein was 40 and 57
      for AMV-2 and Bhimili-1 varieties respectively. Mesta seed oil is rich in
      unsaturate fatty acids (70%), of which linoleic acid constituted 44%. Weanling
      rats were fed with 10% mesta seed protein before and after cooking for 4 weeks.
      Food intake of animals receiving raw mesta seed diets was significantly lower
      than those receiving cooked mesta seed diets as well as the casein control diet.
      Protein and dry matter digestibilities of raw and cooked mesta seed diets were
      lower than that of casein control diet. Cooking improved the food intake, gain in
      body weight, dry matte and protein digestibility of mesta seed diets. PER and NPU
      of cooked mesta seed diets were significantly higher than the corresponding raw
      diets. These results indicate that cooked mesta seed protein is of relatively
      good quality.

PMID- 9139302
TI  - Chemical composition and nutritional potential of yam bean seeds (Pachyrhizus
      erosus L. urban).
AB  - Pachyrhizus erosus seeds were analysed for proximate composition, minerals,
      protein fractions, antinutritional factors, and rotenoids. The seeds showed a
      high content of proteins, lipids, Fe and Ca, in comparison to other legumes.
      Glutelins constitute the highest protein fraction, followed by globulins.
      Antinutritional substances detected as tannins, hemagglutinating activity and
      trypsin inhibitory activity, were in low concentrations. Seeds were also
      processed to obtain a flour which showed proper characteristics, good in vitro
      digestibility, significant rotenoid reduction level and amino acid composition
      rich in essential amino acids, except methionine.

PMID- 9139303
TI  - Effect of domestic processing on the cooking time, nutrients, antinutrients and
      in vitro protein digestibility of the African yambean (Sphenostylis stenocarpa).
AB  - The effects of processing (soaking, dehulling, fermentation and heat treatment)
      on the cooking time, protein, mineral, tannin, phytate and in vitro protein
      digestibility (IVPD) of the African yambean (AYB) were examined. The cooking time
      ranged from 90-155 minutes. Soaking reduced cooking time by about 50 percent.
      Soaking for 12 hours was the most appropriate to reduce cooking time, tannin and
      phytate levels. It improved in vitro protein digestibility (IVPD). Prolonged
      soaking (24 hours) decreased calcium (Ca) and iron (Fe) values by 19 percent and
      35 percent, respectively. Dehulling showed that Ca, Fe, magnesium (Mg) and zinc
      (Zn) were concentrated in the seed coat of the AYB. The seeds soaked and dehulled
      retained Mg and Zn. Dehulling reduced tannin but had no significant effect on
      phytate and the IVPD of the AYB except for seeds soaked for 12 hours before
      dehulling. Soaking for 24 hours before dehulling significantly increased crude
      protein content by 16 percent (p < 0.05). Blanching and roasting increased the
      IVPD by 8-11 percent. Fermentation had no effect on the crude protein, Ca, Fe, Mg
      and Zn but significantly reduced phytate content of the AYB. Fermentation had no
      advantage over heat treatment with respect to improving the in vitro protein
      digestibility of the AYB.

PMID- 9139304
TI  - Effects of altitude above sea level on the cooking time and nutritional value of
      common beans.
AB  - The present study was conducted with the objective to determine the effects of
      altitude above sea level, on the cooking time and nutritional value of common
      black beans (Phaseolus vulgaris). Three 100 g samples of the Ostua variety were
      cooked at 8 individual locations, ranging in altitude from 0 to 2256 meters, in
      Guatemala, to establish water uptake and cooking time. The cooked samples were
      separated into cooked beans and cooking broth for chemical analysis. This
      included moisture, protein, lysine, tannins, total and enzyme susceptible starch,
      and fiber fractionation. The cooking liquor was analyzed for total solids,
      moisture, protein, ash and K. A 1200 g sample was cooked for the cooking time
      established previously, for biological testing of nutritional value, which
      included Net Protein Ratio (NPR), Protein Efficiency Ratio (PER), and protein
      digestibility. Altitude influenced cooking time which increased from 78 min at 0
      m, to 264 min at 2256 m. Final moisture content in the cooked bean was similar at
      all altitudes and there was a tendency to yield smaller amounts of solids in the
      cooking broth at higher altitudes. The increase in cooking time was significant.
      Bean water uptake at all times was significantly slower and smaller at ambient as
      compared to water uptake at boiling T, at all altitudes. Protein and lysine
      content were not affected by altitude, however, tannin and catechin were lower in
      cooked samples, as compared to the raw material. Altitude did not affect the
      content of these substances. Total starch and total sugars were higher in the raw
      sample, as compared to the cooked samples, but there was no effect of altitude.
      Enzyme susceptible starch (ESS) was lower in the raw sample as compared to the
      cooked samples, which contained similar amounts with respect to altitude. No
      change was observed in fiber fractions of the cooked beans. Likewise, the
      composition of the cooking broth was very similar between cooking locations.
      There was a small tendency to a lower protein quality, with respect to altitude,
      the effect of which was more obvious in the apparent protein digestibility
      values. Undercooking or overcooking at one location influenced protein quality
      values. The extended cooking time of beans at high altitudes, has important
      economic and environmental implications, since significant amounts of wood have
      to be used.

PMID- 9139305
TI  - Three edible wild mushrooms from Nigeria: their proximate and mineral
      composition.
AB  - The pilei (caps) and the stipes (stalks) of the button and early open-cap (cup)
      stages of Lentinus subnudus, Psathyrella atroumbonata and Termitomyces striatus
      were assayed separately for their proximate and mineral composition. The
      differences observed in the contents of some of the proximate components seem to
      be related to species and mushroom parts. P. atroumbonata was richest in crude
      and true protein, L. subnudus was richer in crude fiber, ash and carbohydrates.
      Mineral contents appeared to be dependent on type and parts of the mushrooms
      analysed. The three mushrooms were good sources of magnesium, zinc and iron. L.
      subnudus contained between 14.83 and 20.00 ppm of iron, P. atroumbonata contained
      between 20.01 and 22.09 ppm and T. striatus contained between 17.13 and 22.93 ppm
      of iron. The pilei of P. atroumbonata and T. striatus are very good sources of
      zinc. Zinc contents for the pilei of P. atroumbonata were 63.81 and 64.94 ppm
      respectively. Zinc contents for T. striatus were 90.45 and 92.49 ppm
      respectively.

PMID- 9139306
TI  - Red palm oil as a source of beta-carotene for combating vitamin A deficiency.
AB  - Twenty four school children of 7-9 years of age were divided into two groups of
      six boys and six girls each. One group was given a daily supplement of 'Suji
      halwa', a sweet snack made with semolina and red palm oil, supplying 2400 mu g of
      beta-carotene and the second group was the control group which was given 600 mu g
      of oral vitamin A palmitate, for 60 days. Vitamin A status before and after
      supplementation was assessed by the Modified Relative Dose Response Assay (MRDR).
      Results indicated that serum vitamin A levels increased from the basal level of
      0.86 +/- 0.13 mu m mol/l to 1.891 +/- 0.23 mu mol/l in the Red Palmoil (RPO)
      group and from 0.74 +/- 0.09 to 1.94 +/- 0.21 mu mol/l in the control vitamin A
      group. Dehydroretinol/Retinol (DR/R) ratio decreased from 0.073 +/- 0.025 to
      0.023 +/- 0.004 in the RPO group and from 0.090 +/- 0.023 to 0.023 +/- 0.004 in
      the vitamin A group, indicating liver saturation with vitamin A after feeding RPO
      snacks, comparable to synthetic vitamin A. This study indicates that RPO is an
      efficient source of beta-carotene which is found to be bioavailable in all the
      subjects tested, hence it can be used for supplementary feeding programmes to
      combat vitamin A deficiency in target population.

PMID- 9139307
TI  - Effect of Egyptian cooking methods of faba beans on its nutritive value, dietary
      protein utilization and iron deficiency anemia. 1. The role of main technological
      pretreatments.
AB  - In order to study the effects of main technological pretreatments practised for
      preparing Egyptian faba bean products, i.e. decortication as well as soaking and
      germination followed by dehulling on the nutritional value, series of experiments
      were carried out. Such pretreatments had a significant effect on the changes in
      the chemical composition of faba beans. The proportion of the removed hulls
      reached generally about 14%. Data revealed also pronounced improvements on the
      nutritive value as a result of all studied pretreatments, especially germination
      being the most effective. Chemical scoring of all determined essential amino
      acids was > 60, except methionine and cystine showed the lowest score (< 20).
      Germinated seeds had the highest chemical score for the restricting amino acids
      beside the lowest GDR value [Grams consumed of product to cover the daily
      requirements for adult man in protein (63 g) and in energy (2900 kcal)]. All
      pretreatments caused a significant decrease in the antinutritional factors,
      especially soaking followed by dehulling, whereas decortication led to a
      significant increase in phytic acid content.

PMID- 9139308
TI  - [Sarcoidosis in a patient with Crohn disease].

PMID- 9139309
TI  - [Purification of angiogenin from cow's milk].
AB  - A new method for the purification of bovine angiogenin is proposed which is based
      on the use of CM-cellulose, CM-Toyopearl, and Butyl-Toyopearl.
      Electrophoretically homogeneous protein was obtained with a 49% yield and 12,000
      fold purification.

PMID- 9139310
TI  - [Combination of the sieve effect and ion exchange chromatography during isolation
      of recombinant alpha2-interferon on the cellosorbent CS KU-23].
AB  - Preliminary purification of alpha 2-interferon from the culture liquid on cation
      exchange sorbents was studied. Application of a cellosorbent based on the
      cationite KU-23 resulted in a 20-25-fold purification of recombinant alpha 2
      interferon in a one-step process as a result of combination of the sieve effect
      and ion-exchange chromatography.

PMID- 9139311
TI  - [Comparative characteristics of microbial proteases by the level of hydrolysis of
      protein substrates].
AB  - Screening of enzyme preparations displaying a maximum proteolytic activity at pH
      4.0-5.5 and effecting deep proteolysis of plant proteins was performed.
      Amyloprotooryzin prepared from Aspergillus oryzae 387 containing a complex of
      proteolytic enzymes was the most effective. The amino acid composition of the
      hydrolysates obtained was studied. Amyloprotooryzin increased the contents of
      amino acids by 108-227%, depending on the substrate used. The enzymatic complex
      of amyloprotooryzin was studied; in addition, proteases, alpha-amylase, exo-beta
      glucanase, and xylanase were detected in the complex.

PMID- 9139312
TI  - Models of health care.
AB  - Using nursing models is part of the systematic decision-making that underpins
      nursing practice. Using a health-care model is a central feature of being a
      responsible practitioner. Part 3 of this module considers a number of models of
      health care.

PMID- 9139313
TI  - [Psychopathological study on lying motive--specific mood of depersonalization in
      manic depression].

PMID- 9139314
TI  - Regression: a reconsideration of topographic theory.

PMID- 9139316
TI  - Psychoanalysis and Kabbalah.

PMID- 9139315
TI  - Deception, mystification, trauma: Laing and Freud.

PMID- 9139317
TI  - Transitional phenomena, transitional space: creativity and spectatorship in film.

PMID- 9139318
TI  - Beyond the yellow brick road: the reconstitution of the material past in Peggy
      Sue Got Married.

PMID- 9139319
TI  - Anatomy of soul murder, Part II: Family romance and structure of delusion in the
      memoirs of D. P. Schreber.

PMID- 9139320
TI  - The construction of the world in psychosis.

PMID- 9139321
TI  - [Body image disturbances in patients with anorexia nervosa 12 years after
      clinical consultation].
AB  - Of 103 patients with anorexia nervosa, 50 women and 5 men were followed-up on the
      average 11.8 year after clinical presentation with a differentiated method for
      body awareness according to Askevold. A considerable number of women with body
      image disturbances, however, largely corresponded to those of a healthy female
      control group. Both the male anorexia nervosa patients and the healthy male
      controls had normal findings. Applying to touch-induced stimulus, the body
      assessment indices only increased in former male anorexia patients but remained
      the same in female anorexia patients, while they clearly normalized in the sense
      of a realistic assessment in the two healthy control groups. Surprisingly, there
      was only little correlation between the visually measured body perception
      disorder and the self (EDI) and expert assessment (Sianex) at the time of follow
      up (exception: the EDI scale 3 [dissatisfaction with one's own body). The global
      expert rating of body image disturbances at clinical presentation was important
      as a predictor for the severity of anorexia nervosa after 12 years. The findings
      were discussed under methodological and clinical aspects.

PMID- 9139322
TI  - [Structured day care therapy program for eating disorders].
AB  - A day hospital group treatment program is detailed which could offer effective
      treatment to many patients with anorexia nervosa and bulimia nervosa who would
      otherwise require inpatient treatment. Important clinical advantages over an
      inpatient program are described. The psychotherapy is cognitive-behavioral
      oriented and is done in groups. A multi-disciplinary team approach is used. The
      day hospital treatment program includes psychological, social and eating-related
      interventions. Main characteristics are the motivation-phase, the contact between
      patients of different therapy-phases, the involvement of families in therapy and
      the support of self-help. First empirical outcome results are presented.

PMID- 9139323
TI  - [Significance of membership in new religious movements for regulation of self
      concept exemplified by the Hare Krischna movement].
AB  - 222 members of the Hare-Krishna-Movement were investigated with the Narcissism
      Inventory by Deneke and Hilgenstock (1989). The results show that life in the
      Hare-Krishna-Movement makes certain defensive functions possible. The Hare
      Krishnas seem to reach a stabilization of their self experience through
      idealizing transferences and overemphasizing their value-system. High scores on
      the scale derealisation/depersonalisation hint at an ego-weakness of the members.

PMID- 9139324
TI  - [Psychological classification of functional voice disorders].
AB  - In an explorative study the classification of a collective of patients with
      different voice disorders by discriminant and cluster analysis was tried. 21
      variables, obtained from 128 patients with various diagnoses of voice disorders,
      were used. A first discriminant analysis on the basis of diagnoses-groups
      permitted no differentiation. A subsequent hierarchical cluster analysis
      indicated a four-cluster-solution. The clusters showed only little association
      with the phoniatric diagnoses. Cluster 1 is characterized by patients with non
      organic voice disorders. Cluster 2 is marked by emotional unstable patients with
      organic dysphonia. Cluster 3 consists of patients with psychosomatic dysphonia by
      laryngeal contact granuloma, and cluster 4 contains emotional stable patients
      suffering from organic dysphonia and from spasmodic dysphonia. Thirteen
      psychological variables discriminated the clusters significantly: Anxiety about
      appearing in public, emotionality (neuroticism), life satisfaction,
      aggressiveness, anxiety, about physical injuries, extraversion.

PMID- 9139325
TI  - [Depressive affect and surrogate markers in HIV infected patients].
AB  - The present study investigates whether there is a relationship between subjective
      well-being and the change of immune markers in HIV-infected subjects. Twenty-one
      HIV-infected persons completed questionnaires. Immune markers (CD4-percentage and
      CD4/CD8-ratio) were measured at the beginning of the study, after 8 months and
      after 15 months. In a hierarchical multiple regression model, baseline values of
      immune markers explained most of the variance of the immune markers, both after 8
      and 15 months. After including several control variables in the model, depression
      values and the values on the symptom checklist explained an additional increment
      of variance of both immune markers after eight months. Therefore, data of the
      present study suggest that predominantly depressive feelings co-determine immune
      status in HIV-infected persons.

PMID- 9139326
TI  - Lymphoma of the esophagus.

PMID- 9139327
TI  - Plagiarism, horn blowing, and the history of ideas.

PMID- 9139328
TI  - [The pharmacological treatment of acute coronary syndromes].

PMID- 9139329
TI  - [Antithrombotic drugs in the acute coronary syndrome].

PMID- 9139331
TI  - [Angioplasty in the acute coronary syndrome].

PMID- 9139330
TI  - [The cellular and molecular bases of the acute coronary syndrome].

PMID- 9139332
TI  - [The anti-ischemic effects of ACE inhibitors after an acute myocardial infarct].

PMID- 9139333
TI  - [The reduction of cardiovascular events after a myocardial infarct in patients
      with normal cholesterol levels].

PMID- 9139334
TI  - [Post myocardial infarct. The therapeutic decisions on hospital discharge in
      Spain (the PREVESE study). Prevencion Secundaria en Espana].

PMID- 9139336
TI  - [Epidemiology. Secondary cardiovascular prevention].

PMID- 9139335
TI  - [Plaque vulnerability and disruption].

PMID- 9139337
TI  - [What is your diagnosis?].

PMID- 9139338
TI  - [Ventricular hypertrophy and cardiac insufficiency: current treatment based on
      recent physiopathological discoveries].

PMID- 9139339
TI  - [Pathophysiology of left ventricular hypertrophy in arterial hypertension].
AB  - The role of left ventricular hypertrophy as an independent risk factor for
      subsequent cardio-vascular events is well established, therefore the authors, in
      this brief review, describe the endocrine function of the heart and the role
      played by various factors, including hormones, in the development of cardiac
      remodeling during the course of hypertension. They then outline the present state
      of our knowledge concerning transmembrane signaling in the cardiomyocyte in
      response to an activation of specific receptors for vasoactive hormones of the
      renin-angiotensin II-aldosterone system.

PMID- 9139341
TI  - [Endothelial factors and cardiac insufficiency].
AB  - The endothelium produces several vasodilating factors such as prostacyclin or
      nitric oxide and also vasoconstricting agents such as endothelin. These factors
      play an important role in the regulation of vascular tone and tissue perfusion.
      Several recent studies have evaluated the role of endothelin and NO in the
      pathophysiology of congestive heart failure. This paper reviews the data
      suggesting that endothelin and NO contribute to the neuro-hormonal compensatory
      mechanisms in patients with heart failure and that specific blockade of
      endothelin receptors could be an effective new approach for the treatment of
      patients with severe congestive heart failure.

PMID- 9139340
TI  - [Hypertrophy due to left cardiac insufficiency: role of the neurohumoral system].
AB  - Left ventricular hypertrophy in patients with hypertensive heart disease is
      associated with impaired relaxation and myocardial interstitial fibrosis leading
      to enhanced filling pressure, referred to as left ventricular diastolic
      dysfunction. Impairment of systolic function, characterized by reduced ejection
      fraction occurs at a later stage. Activation of the renin-angiotensin-aldosterone
      system contributes to progression to heart failure by at least two mechanisms:
      (1) increased left ventricular loading conditions due to vasoconstriction and
      retention of sodium; (2) direct effects on the myocardium resulting in myocyte
      hypertrophy and interstitial fibrosis.

PMID- 9139343
TI  - [Assessment of cardiac insufficiency].
AB  - Heart failure is a common clinical syndrome caused by different cardiovascular
      diseases. The prognosis is poor once the stage of congestive failure is reached.
      Several non-invasive and invasive techniques, described in this article, are used
      to objectively diagnose systolic or diastolic failure at its early stage. These
      investigations are needed to assess, not only the cardiac dysfunction, but also
      the underlying cause of the failure. Early and effective treatment should prevent
      or delay the occurrence of the signs of congestive failure and thus improve the
      prognosis.

PMID- 9139342
TI  - [Diastolic dysfunction of the left ventricle: from physiopathology to treatment].
AB  - Our understanding of cardiac failure has greatly changed over the last 15 years.
      Left ventricular diastolic dysfunction, which is now recognised as one of the
      primary causes of certain types of cardiac failure (1). Abnormal left ventricular
      diastolic function is the common determinant and indeed the earliest sign of all
      chronic left ventricular failures whether systolic left ventricular dysfunction
      is associated with it or not (2). In this paper, we review the basis of diastolic
      dysfunction and its impact on diagnosis and treatment of cardiac failure.

PMID- 9139344
TI  - [Drug treatment of cardiac insufficiency with systolic dysfunction].
AB  - Improvement of symptoms, increase in exercise capacity and prevention of disease
      progression are the aims of drug therapy in patients with congestive heart
      failure. At present only the ACE inhibitors are able to achieve all therapeutic
      targets and should therefore be regarded as drugs of first choice in systolic
      dysfunction. Diuretics are also necessary in most patients since they rapidly
      reduce pulmonary congestion and peripheral oedema, but have no documented
      beneficial long term effects on the course of CHF. Digoxin remains a useful drug
      to treat symptomatic patients who do not respond adequately to the combination of
      ACE inhibitors and diuretics, as well as in patients with atrial fibrillation.
      However, a reduction of mortality by digitalis glycosides cannot be expected. A
      new trend in the treatment of CHF is the utilisation of beta blockers. These
      drugs showed positive effects in chronic CHF in several studies, particularly in
      patients with dilated cardiomyopathy. Newer drugs such as carvedilol, seem to
      improve the symptoms and reduce complications even in CHF due to coronary artery
      disease. The role of beta blockers in the routine management of patients with
      heart failure requires further evaluation.

PMID- 9139345
TI  - [Should every patient with atrial fibrillation get anticoagulants?].
AB  - Embolic complications are very common in patients with atrial fibrillation.
      Patients over 60 years with organic heart disease, arterial hypertension,
      diabetes mellitus and previous embolic complications are prone to embolic
      complications. In these high risk groups anticoagulation should be introduced
      when no contraindications exist. Long term anticoagulation therapy should be
      evaluated for each patient individually balancing pro and contra. For patients
      with a low risk of embolism aspirin is a valuable alternative to anticoagulation.
      Patients below 60 years without heart disease and without additional risks do not
      need any therapy.

PMID- 9139346
TI  - [Hip pain].

PMID- 9139347
TI  - [Recurrent dyspnea attacks, urticaria, epigastric symptoms and eosinophilia].

PMID- 9139348
TI  - [Mono- ad polychemotherapy in HIV infection].

PMID- 9139349
TI  - Ethics: sending out the message.

PMID- 9139350
TI  - SV40 and human cancer.

PMID- 9139351
TI  - On punctuated equilibria.

PMID- 9139352
TI  - Lobbyists seek to reslice NIH's pie.

PMID- 9139353
TI  - AIDS: a justifiable share.

PMID- 9139355
TI  - An ocean emerges on Europa.

PMID- 9139354
TI  - New study says low-fat diet can lower blood pressure.

PMID- 9139356
TI  - Paleoanthropology. Miocene primates go ape.

PMID- 9139357
TI  - Herbert Benson: mind-body maverick pushes the envelope.

PMID- 9139358
TI  - Antigen presentation by memory B cells: the sting is in the tail.

PMID- 9139359
TI  - Externalities and economic realities: a macrochallenge for health economics.

PMID- 9139360
TI  - Mitochondrial cytochrome b gene in two developmental stages of human malarial
      parasite Plasmodium falciparum.
AB  - The cytochrome b gene of the mitochondrial ubiquinol-cytochrome c reductase
      (complex III of electron transport chain) was characterized in two developmental
      stages of human malarial parasite cultivated in vitro. The cytochrome b gene
      spanning the nucleotide position 4691 to 5930 in 6-kb mitochondrial DNA from
      gametocytic (sexual) and intraerythrocytic (asexual) stages of Plasmodium
      falciparum (a T9,94 mutant line) were in vitro amplified from total DNA using
      polymerase chain reaction (PCR). It was found that the parasites from both stages
      contained the PCR product approximately 1.2 kb in length that was localized in
      mitochondria. The nucleotide sequences of cytochrome b gene at Qi/quinone binding
      site from both stages were analyzed using thermal cycle sequencing and were found
      to be the same. The amount of this gene from both stages of the parasite were
      determined by using the quantitative PCR method. The results showed that the
      amount of the cytochrome b gene produced from the sexual stage was seven times
      higher than that obtained from the asexual stage. Our results would provide basic
      information on the regulation of cytochrome b and the 6-kb mitochondrial DNA
      during growth and development of the sexual and asexual stages of the malarial
      parasite in the mammalian host.

PMID- 9139361
TI  - Development of cultivation technique for pure Plasmodium falciparum gametocytes.
AB  - Pure gametocyte culture of Plasmodium falciparum, isolate KT3, from Kanchanaburi
      Province, Thailand, was successfully established by 5% sorbitol treatment on days
      9, 10 and 11 following initiation of culture. Using medium supplemented with 15%
      human plasma and activated erythrocytes, daily medium change was not required
      during the cultivation. There was 99% reduction in the numbers of asexual
      parasites in the culture but the numbers of gametocytes were not affected.
      Furthermore, the gametocytes could undergo their usual morphological development
      with retention of function as demonstrated by the appearance of exflagellating
      microgametocytes, macrogametocytes and of oocyst formation in midgut of infected
      mosquito.

PMID- 9139362
TI  - Identifying malaria control issues: a district hospital-based evaluation.
AB  - Chuk district hospital is centrally located in a rural malarious region in
      southern Cambodia. It was the site of a hospital-based evaluation (KAP assessment
      and in vivo i.v. quinine/oral tetracycline drug study) done to identify relevant
      issues for establishing a rational malaria control strategy. The KAP assessment
      identified the young, male forest worker as the highest risk group. Of 112 study
      patients, 73% were male and 82% reported various forest activities. The primary
      reason found for patient delay (8.9 days) in seeking hospital care was self
      treatment at home (N = 102, 91%) with drugs purchased through private sellers
      (104/105). Using the 7-day WHO field test methodology, resistance rates were
      calculated (N = 22); S1/R1, 73%; R1, 9%; R2, 0%; R3, 18%. A modified version of
      the 7-day test was used to calculate its utility in this particular rural
      setting. It showed a negative predictive value of 93% and a positive predictive
      value of 71%. The case fatality rate for the study period was 2.7%. Information
      from this study, which correlates a confirmed malaria diagnosis with prior
      patient behavior and response to anti-malarial therapy, is intended for realizing
      the goals set forth by the national malaria control program.

PMID- 9139363
TI  - Differentiation of Salmonella typhi strains by ribosomal RNA gene restriction
      patterns.
AB  - Owing to the limited value of phage typing to determine the epidemiological
      association of Salmonella typhi (S. typhi) strains isolated from the source of
      typhoid fever, we analyzed ribosomal RNA (rRNA) gene restriction patterns to
      differentiate the independently isolated strains of identical phage type. The
      data showed that the restriction patterns of PstI was most polymorphic among four
      enzymes (BamHI, EcoRI, PstI, and SmaI) used, which revealed 13 types among 25
      strains belonged to 4 phage types, 1 untypable and 2 not-determined strains.
      Total 25 strains of S. typhi were divided into 15 combination types by the rRNA
      restriction patterns with three enzymes (BamHI, PstI, and SmaI).

PMID- 9139364
TI  - Retrospective review of dot enzyme immunoassay test for typhoid fever in an
      endemic area.
AB  - Typhoid fever remains a common problem in Malaysia, but for its diagnosis both
      blood culture and the Widal test have drawbacks. A dot enzyme immunoassay (EIA)
      has been developed which detects IgM and IgG antibodies to a specific 50 kDa
      outer membrane protein on Salmonella typhi. This study was performed among
      outpatients attending the university hospital in Kelantan, a state on the east
      coast of Peninsular Malaysia where typhoid is endemic. The dot EIA was done on
      149 outpatients of all ages in whom typhoid was suspected. Of these, 60 were not
      analysable due to insufficient data. The other 89 were retrospectively classed as
      typhoid (total = 21), or not typhoid (total = 68). The criteria for diagnosis of
      typhoid was either, blood culture was positive, or with blood culture negative,
      temperature was at least 38 degrees C and Widal O and/or H titer greater than or
      equal to 1/160. We then compared the diagnosis with the EIA result. For the
      result where either IgM or IgG was positive, sensitivity was 90%, specificity 91%
      and negative predictive value 97%. For IgM positive, specificity was 100%. But
      the specificity of IgG positive alone was reduced by six false positives, which
      were probably due to persistence of IgG after acute infection. Other cases were
      found where IgG positive alone appeared in the first week of typhoid fever,
      probably due to rapid response in a second or subsequent infection. We also found
      that IgM-producing patients were significantly younger than those showing IgG
      alone positive.

PMID- 9139365
TI  - Evaluation of the Mycobacterium leprae particle agglutination (MLPA) test as a
      tool in the epidemiology of leprosy in high prevalence village in South Sulawesi,
      Indonesia.
AB  - This study reports on the usefulness of an IgM phenolic glycolipid-1 (PGL-1)
      Mycobacterium leprae particle agglutination (MLPA) test for serodiagnosis of
      leprosy in a prospective longitudinal community survey in a high prevalence
      village in South Sulawesi, Indonesia, IgM PGL-1 MLPA has simple and limited value
      as a screening method for detection of transmission of leprosy in the community.
      Many normal persons in the community in a high prevalence area had increased IgM
      anti PGL-1 antibodies, presumably as a consequence of early subclinical
      infection. In conclusion, this study demonstrated that the MLPA test can only
      reliably detect anti-PGL-1 antibodies in the community and may be useful for
      follow-up study of subclinical infection of leprosy among individuals living the
      an endemic area.

PMID- 9139366
TI  - Geographical distribution of Pseudomonas pseudomallei in China.
AB  - 1,366 samples of soil and water from southern China coastal provinces were
      examined for Pseudomonas pseudomallei. Data showed that 58 samples were positive
      for this bacteria, which is primarily distributed in Hainan Province and the
      coastal region of mainland. This paper confirmed the environmental presence of P.
      pseudomallei in China and showed that the distribution of this pathogen has at
      least reached a latitude of 25.5 degrees north.

PMID- 9139367
TI  - Use of serum bactericidal activity in assessing previous antibiotic therapy in
      acute lower respiratory tract infection in children.
AB  - Bactericidal activity in sera of children with acute lower respiratory tract
      infection was assayed to determine its effect on the outcome of blood culture.
      Parental reporting of prior antibiotic therapy was also determined. 14.4% of
      samples without serum bactericidal activity yielded pathogens from blood culture,
      whereas only 2.4% of samples with serum bactericidal activity yielded pathogens.
      A statistically significant correlation was found between isolation of pathogens
      by blood culture and serum bactericidal activity. Parental reporting could not be
      relied upon as there was no positive correlation.

PMID- 9139369
TI  - An assessment of barangay health midwives' knowledge regarding tuberculosis case
      finding and treatment procedures in urban health centers of metropolitan Manila,
      Philippines.
AB  - A survey was done from August to September, 1992 to determine the level of
      knowledge of 48 barangay health midwives (BHW) from urban health centers in
      Metropolitan Manila with regards to tuberculosis case finding and treatment
      procedures, as recommended by the National Tuberculosis Control Program (NTCP) of
      the Department of Health. Questionnaires were administered by personal interview.
      A cut-off mark of 17 correct answers out of 23 or 74% was arbritrarily chosen to
      signify a satisfactory level of knowledge. Results revealed that a substantial
      proportion of midwives still have inadequate knowledge regarding casefinding,
      case holding and NTCP policies. Type of training (p < 0.01) and age (p < 0.05)
      were found to be significant factors affecting level of knowledge while length of
      service was found to be marginally insignificant (p = 0.06). It is therefore
      highly recommended that urban health midwives be subjected to more regular formal
      training to increase their level of competence in attaining the goals of the
      NTCP.

PMID- 9139368
TI  - Prevalence of tuberculosis in Vietnamese migrants: the experience of the Orderly
      Departure Program.
AB  - This study aimed to describe the Internal Organization for Migration (IOM)
      tuberculosis screening and treatment program in Ho-Chi-Minh City (Vietnam); and
      to review the prevalence of tuberculosis and treatment outcome in a cohort of
      Vietnamese migrants and refugees prior to their departure. From 1 November 1992
      to 1 June 1993, prospective migrants and refugees bound to the United States,
      Australia, and Canada underwent medical examination by IOM in Ho-Chi-Minh City.
      Screening for tuberculosis was based on chest x-rays, and the diagnosis was
      confirmed by smear examination. Smear-positive patients received short-course
      chemotherapy, directly supervised, with isoniazid, rifampicin, ethambutol, and
      pyrazinamide. Out of 39,581 persons screened, 322 were smear-positive (641 per
      100,000), and started treatment. Follow-up varied from a minimum of 12 months to
      a maximum of 18 months. At that time, 265 (82%) were cured, while the remaining
      either continued treatment with first-line drugs (24), started second-line
      treatment (17), or failed to be cured for various reasons (16). This report
      confirms the efficacy of short course chemotherapy and directly observed
      treatment for tuberculosis, in the context of one of the largest screening
      programs for prospective migrants. Follow-up in receiving countries would help
      clarify risk factors for both new infection and relapse of tuberculosis.

PMID- 9139370
TI  - Toxoplasma infection in healthy persons and in patients with HIV or ocular
      disease.
AB  - Toxoplasma infection is associated with acquired immune deficiency syndrome
      (AIDS), pregnancy, chorioretinitis, etc. Since the number of AIDS patients is
      increasing rapidly in Thailand and there are few reports about T. gondii immune
      status in this country. Toxoplasma-specific IgG and IgM antibodies (Ab) were
      determined in healthy persons and patients with different symptoms who were
      suspected of toxoplasmosis. Specific IgG Ab were detected in 3.2% of healthy
      persons, 12.5% of patients with ocular disease and in 42.5% in HIV positive
      patients. Only 3.1% of patients with ocular disease were positive for specific
      IgM Ab. No specific IgM Ab were found in the other samples studied.

PMID- 9139371
TI  - Perinatal HIV infections in Thailand.
AB  - A collaborative study group of researchers from seven hospitals from all regions
      of Thailand was formed to collect information on children born to HIV-infected
      mothers since the beginning of the first hospital case until the end of June
      1994. The study conducted to verify the status of perinatal transmission of HIV
      infection in Thailand showed a rapid increase in HIV seropositivity among Thai
      mothers with vertical transmission rates varying between 25% in Rayong and 42% in
      Chiang Rai Hospitals, respectively. The majority of children with symptomatic HIV
      infection had clinical presentations of delayed growth development, pneumonia,
      diarrhea, oral candidiasis, lymphadenopathy, hepato-splenomegaly. Cases of
      Penicillium marneffei infection were found only at Chiang Rai Prachanukroh
      Hospital. The ages at which diagnosis of HIV disease was made were mostly within
      the first year of life. One third of children with AIDS died during the period of
      study.

PMID- 9139372
TI  - Genotype determination of three dengue type 2 virus strains from Myanmar by
      sequencing E/NSI gene junction.
AB  - Genotype of three dengue-2 virus strains from Myanmar was determined as genotype
      II by sequencing 240 nucleotide long fragment across the E/NS1 gene junction by
      the primer extension dideoxy chain termination method, applying direct sequencing
      of the PCR product. These strains were isolated from a dengue shock syndrome
      (DSS) patient and two patients with dengue hemorrhagic fever (DHF) grade 1, in
      Yangon (Rangoon), Myanmar (Burma), in 1987. Sequence homology of all three
      strains were highest (96%) to New Guinea C strain (genotype II), lesser homology
      (93%) to Jamaican 1409 strain (genotype III), and the least homology (91%) to PR
      159/S1 strain (genotype I). Two DHF strains revealed only 2 nucleotide and 3
      nucleotide differences compared with DSS strain, all at the 3rd position of the
      codons which resulted in silent mutations.

PMID- 9139373
TI  - The use of polymerase chain reaction (PCR) as a diagnostic tool for dengue virus.
AB  - This study describes the use of polymerase chain reaction as a diagnostic tool
      for detecting and typing of dengue virus. PCR was compared against virus
      isolation. First RT-PCR was done using dengue consensus primers after which
      positive samples were subjected to RT-PCR using type-specific primers. This study
      shows that the local strains of the dengue virus could be detected using the
      chosen primers. Furthermore, RT-PCR was found to be more sensitive than virus
      isolation in identifying the dengue positive samples.

PMID- 9139374
TI  - Anti-dengue IgG detection by an indirect ELISA.
AB  - Protein-free culture media were originally developed for hybridomas to simplify
      downstream processing and purification. For the same reasons, we have used these
      protein-free media for passaging dengue 2 virus in C6/36 cells. This provided us
      with an infected supernatant (DenPF) which could then be used as coating antigens
      for an indirect enzyme-linked immunosorbent assay (ELISA) to determine dengue IgG
      levels. Using this preparation, the main immunogenic band as seen by immunoblot
      appeared to be viral envelope protein (E). Without the high concentrations of
      "competing" proteins from fetal calf serum (FCS), the Den2PF could be directly
      coated onto 96-well ELISA plates. The amount of viral proteins in Den2PF appeared
      to be sufficient so that there was no need for further purification steps, eg
      polyethylene glycol (PEG) precipitation, which made this preparation cost
      effective. It compared favorably with the dengue dot enzyme immunoassay (DEIA;
      sensitivity of 95.7% and specificity of 95.2%).

PMID- 9139375
TI  - Genome differences among varicella-zoster viruses isolated in Thailand.
AB  - The DNAs of 17 isolates of varicella-zoster virus (VZV) obtained from 17 Thai
      individuals with normal varicella or zoster infections (no underlying diseases)
      were compared by restriction endonuclease analysis using BglI, PstI, EcoRI, SmaI
      and BamHI. The DNA of the Japanese strain, Kawaguchi, was also conducted as a
      reference DNA. All of virus isolates were confirmed for existence of VZV and VZV
      DNA by immunofluorescent test and DNA-hybridization, respectively. Almost all of
      the Thai epidemiologically unrelated isolates and the Kawaguchi strain could be
      individually differentiated using BglI, PstI, and EcoRI. The other two isolates
      were identical in restriction profiles even after five endonuclease digestions
      which SmaI and BamHI were the two more enzymes used, therefore, they could be
      discriminated totally into 16 strains from overall 17 isolates. These findings
      demonstrate the strain variation of wild-type varicella-zoster viruses isolated
      in Thailand.

PMID- 9139376
TI  - Detection of respiratory syncytial virus from clinical specimens: comparison
      between reverse transcription polymerase chain reaction and tissue culture.
AB  - RT-PCR was compared with tissue culture to detect RSV from nasopharyngeal
      aspirates. RT-PCR was more sensitive and specific than tissue culture method. RT
      PCR has sensitivity and specificity of 100% and 97%, respectively. The results
      indicate that RT-PCR can be used for detection of RSV in clinical specimens.

PMID- 9139377
TI  - A field study on Nakayama and Beijing strains of Japanese encephalitis vaccines.
AB  - A field study to compare the immune response of children aged 1-6 years to
      Nakayama and Beijing strains JE vaccines was carried out in Mae Hong Son
      Province, northwest Thailand, where there was low incidence of JEV infection. The
      first and second dose of each vaccine was given 1-2 weeks apart and the third
      dose was 1 year after the second dose. Seroconversion rate was similarly high,
      about 94% in both groups of vaccinees. At 6 and 12 months after 2 doses of
      vaccines, the seroconversion rates dropped in both groups of vaccinees, so there
      were 10-20% of children (50-65% if cross protection was considered) susceptible
      to JEV infections during this period. After the third dose of vaccine, the
      seroconversion rate rose to 100% in both groups. The GMT in Bejing strain
      vaccinees were slightly higher than Nakayama strain JE vaccines. To reduce the
      number of susceptible children during 6-12 months after the second dose and for
      longer protection, the primary JE immunization should be 3 doses and the timing
      for the third dose should be at 6 months after the second dose. Either Nakayama
      or Beijing strain vaccine could be used in Thailand.

PMID- 9139378
TI  - Prognostic factors of early sequelae and fatal outcome of Japanese encephalitis.
AB  - A clinical case control study to identify prognostic factors present at hospital
      admission associated with early sequelae and fatal outcome of acute Japanese
      encephalitis (JE) was carried out in Gusi county, Henan Province, central China
      from June to September 1991. A total of 70 patients with laboratory-confirmed
      acute JE were studied, of whom 3 cases died and 33 cases had neurological or
      psychiatric sequelae at the end of three months follow-up. The results showed
      that acute JE at younger age, with higher body temperature, high white cell count
      in CSF, and deep coma present at hospital admission were markers for unfavorable
      outcomes (sequelae or fatal). A history of the vaccination was not correlated
      with the early sequelae and fatal outcome of the disease. The paper suggests that
      early diagnosis and treatment and universal JE vaccination for all susceptible
      populations are keys for decreasing incidence of sequelae and fatal outcome of
      acute JE.

PMID- 9139379
TI  - The 1993 epidemic of dengue fever in Mangalore, Karnataka state, India.
AB  - An epidemic of febrile illness with hemorrhagic manifestations occurred in
      certain parts of Mangalore city, Karnataka state, India, from the last week of
      July 1993. The epidemic reached its peak by mid-August and then started
      declining. Sporadic cases, however, continued to occur till early December. About
      200 cases were reported covering all age groups and both sexes. The cases
      presented with pyrexia, myalgia, arthralgia and headache. Palatal petechiae,
      magenta colored tongue with central coating, maculopapular rash and facial flush
      were observed as classical signs. The tourniquet test was positive in 12% of the
      cases. Hemorrhage was observed in the form of epistaxis (2 cases),
      subconjunctival hemorrhage (2 cases) or purpura (3 cases). There were no deaths
      which were attributable to the epidemic. Five strains of dengue (DEN-2) virus
      were recovered from the acute-phase sera. Dengue virus-specific IgM type of
      antibodies were detected in 29/116 (25%) sera. Breeding of Aedes aegypti was
      observed in some of the areas where cases had occurred. No virus was isolated
      from any of the field-caught Ae. aegypti mosquitos.

PMID- 9139380
TI  - Outbreak of hepatitis A in a college traced to contaminated water reservoir in
      cafeteria.
AB  - A sharp but short outbreak of hepatitis A occurred in a college during September
      and October 1992. The epidemic pattern suggested a common source. The attack rate
      of clinically recognizable hepatitis A was 8% all cases were HAV IgM positive.
      Among 31 students with minor symptoms but without jaundice 8 (26%) were also HAV
      IgM positive, as were 8 (10%) of 77 totally asymptomatic students tested. A case
      control study of eating and drinking habits of the students showed no other
      significant differences other than that 45 of 56 cases and 18 of 34 controls
      interviewed had filled their water glasses by dipping them in a overflow water
      reservoir. This gives an odds ratio of 3.8. The reservoir was heavily
      contaminated with coliform bacteria and the residual chlorine was at lower than
      standard concentration, whereas other water resources were clean. It is suggested
      that the reservoir had been contaminated with hepatitis A virus by somebody with
      fecally contaminated hands a couple of weeks prior to the beginning of the
      outbreak.

PMID- 9139381
TI  - Age-specific prevalence of hepatitis A antibody in Thai children.
AB  - Age-specific prevalence of anti-HAV was determined for 3 groups of children whose
      mean ages were 12.6, 20.7 and 52.5 months. There were 41, 43 and 99 children in
      the respective age groups. All children were healthy, from middle to low
      socioeconomic families in Bangkok and vicinity. None of the children in the two
      younger age groups had anti-HAV antibody while 2 of 99 children in the oldest age
      group did. One of them resided in central Bangkok (Amphoe Dusit) and the other in
      Nonthaburi Province. The overall prevalence of anti-HAV in children under 5 years
      old was 1.1%. This demonstrates that hepatitis A transmission rates in Bangkok
      are very low when compared to ten years ago when prevalence rates were as high as
      50-65%. From this study hepatitis A vaccine is recommended for 4-5 years old
      children in Bangkok. We need more epidemiologic data concerning hepatitis A
      transmission in Thailand before we can consider hepatitis A immunization for the
      whole country.

PMID- 9139382
TI  - Detection of circulating antigens of Parastrongylus cantonensis in human sera by
      sandwich ELISA with specific monoclonal antibody.
AB  - A specific monoclonal antibody (AW-3C2) as revealed by ELISA was produced against
      the adult worm antigens of Parastrongylus cantonensis and used in a sandwich
      ELISA for the detection of circulating antigens in the sera of parastrongyliasis
      patients and those with other parasitic diseases. A total of 60 sera was used in
      this study. Of these, 10 each were from patients with parastrongyliasis,
      cysticercosis, filariasis, gnathostomiasis, malaria and toxocariasis. The control
      group consisted of 53 serum samples from normal healthy Thais and Malaysians. The
      mean +/- optical density (OD) values for the normal Thai and Malaysian groups
      were 0.126 +/- 0.028 and 0.124 +/- 0.029, respectively. The mean OD values of the
      parastrongyliasis patient group differed significantly from that of the normal
      groups as well as those of other parasitic infections. Using a cut-off point of
      OD +/- 3SD of the control groups as indicating a positive reading, the
      specificity of the assay with this monoclonal antibody was 100% while the
      sensitivity was 50%.

PMID- 9139383
TI  - Identification of Angiostrongylus cantonensis in infected rats with a
      coagglutination assay.
AB  - The presence of Angiostrongylus cantonensis excretory secretory (ES) products was
      detected in the cerebrospinal fluid (CSF) of infected rats using a
      coagglutination assay. There was clear agglutination in 100% of CSF samples
      tested of the rats infected with third-stage larvae of A. cantonensis and neither
      of the 20 non-infected rats produced agglutination. The assay detected 250 ng/ml
      or more of ES products. This assay is simple, easy to perform with minimum
      training and requires no equipment.

PMID- 9139384
TI  - Intestinal helminthiasis, nutritional status, and their relationship; a cross
      sectional study in urban slum school children in Indonesia.
AB  - In a study of urban slum school children (276 boys and 231 girls), in Ujung
      Pandang, Indonesia, parasitological and anthropometric exams were cross
      sectionally performed to assess prevalence and intensity of helminth infections
      and nutritional status. Prevalence of Ascaris, Trichuris and hookworm was 92%,
      98%, and 1.4%, respectively. 91% children had both Ascaris and Trichuris
      infections. About half of the Ascaris- and Trichuris-infected children (46% and
      58%, respectively) had moderate infections. Stunting was seen in 55% of the
      children, while wasting was observed in 10%. Boys had lower nutritional status
      than girls (p < 0.001), based on weight-for-age (WA) and height-for-age (HA) Z
      scores. Age had an inverse relationship with WA and HA Z-scores (p < 0.0004). A
      relationship between helminth infections and nutritional status was observed
      between log Trichuris egg count and WA and HA Z-scores after controlling for age,
      sex, and log Ascaris egg count (p = 0.048 for HA Z-score, and p = 0.058 for WA Z
      score). The relationship was also found when Trichuris infection was categorized
      into mild, moderate, and severe infections (p = 0.017 and p = 0.001 for HA and WA
      Z-scores, respectively). Scheffe's test for multiple mean comparisons showed that
      Trichuris-infected children with above 1,000 eggs per gram feces had
      significantly lower nutritional status than lower epg or non-infected children (p
      < 0.001 and p < 0.05 for HA and WA Z-scores respectively).

PMID- 9139385
TI  - Contamination of soil with parasite eggs in Surabaya, Indonesia.
AB  - Soil was examined for contamination by parasite eggs in Surabaya Indonesia.
      Surveys were carried out on three occassion; July, 1993 (dry season), March, 1994
      (rainy season), and August, 1994 (dry season). Throughout the study, five species
      of nematode eggs (Ascaris lumbricoides, Toxocara cati, Trichuris trichiura,
      Physaloptera sp, Capillaria sp), two species of cestode eggs (Hymenolepis
      diminuta, Spirometra erinacei), and one species of protozoa oocyst (Isospora
      felis) were detected. The contamination rate and number of species found from the
      soil were significantly different in the dry and rainy seasons. In the dry
      season, the prevalence was 8-20%, with two to four species detected. During the
      rainy season, this rate was 83% with eight species, suggesting parasite infection
      to possibly occur mainly in this season. The reason for this seasonal difference
      may be that, in spite of constant temperature around 27 to 29 degrees C
      throughout the year, rainfall in the dry season in only a few percent of that of
      the rainy season. We concluded that parasite eggs die during the dry season owing
      to dryness of the soil. Contamination of soil with parasite eggs and the number
      of species found were greater in alley-ways and at communal water supply sites
      around residential areas than in open-air parks or sandy beaches. The method used
      in the present study proved extremely effective for ascertaining the actual
      dynamics of parasite infection in a certain region.

PMID- 9139386
TI  - A randomized comparative study of albendazole and thiabendazole in chronic
      strongyloidiasis.
AB  - An open randomized study for comparing the efficacy of albendazole and
      thiabendazole in chronic strongyloidiasis was done in 1990-1992. All 35 patients
      with positive stool examinations for Strongyloides stercoralis were divided
      randomly into two groups. 23 patients (group A) received albendazole (400 mg
      twice daily for 5 days) and 12 patients (group B) received thiabendazole (1 g
      twice daily for 5 days). All patients except four patients in group A were
      admitted in the Hospital for Tropical Diseases for 21 days for monitoring side
      effects (D0-7) and stool examination (D0, D7, 8, 9, D21, 22, 23). Methods of
      stool examination included: direct microscopy of saline smear, formalin ether
      concentration, culture (Harada and Mori method) and larva count (Stool and Sasa
      method). Cure was defined as negative stool examination done at 21 days after
      medication by all above methods. The cure rate for group A was 95% (only one
      failed to clear the parasite at D21) and the cure rate for group B was 100%. But
      there was no statistical difference between the two. Mild changes of transminases
      observed in 5/23 patients who received albendazole, but none developed clinical
      hepatitis.

PMID- 9139387
TI  - Tropical vaginal hydroceles: are they all filarial in origin?
AB  - Hydrocele of the tunica vaginalis testis has been conventionally used as an
      absolute indicator of filarial disease in most clinical surveys. The prevalence
      of filarial etiology in 100 consecutive hydroceles was studied using clinical,
      parasitological, histopathological and immunological parameters. Filarial
      etiology could be proved in 57% of hydrocele cases using major criteria: presence
      of microfilaria in hydrocele fluid, presence of chyle in hydrocele fluid,
      demonstration of adult worm in tunica, ratio of fluid antibody titer to serum
      antibody titer more than 2 and presence of filarial antigen in hydrocele fluid.
      The results of other tests in these 57 cases were used to define the minor
      criteria. In the other 43 cases, based on the minor criteria, 12 hydroceles could
      be classified as likely to be due to filariasis and the rest were probably non
      filarial. Thus only 69% of hydroceles were definitely or probably filarial.

PMID- 9139388
TI  - A new type of advanced third-stage larvae of the genus Gnathostoma in freshwater
      eels, Fluta alba, from Nakhon Nayok, central Thailand.
AB  - Five advanced third-stage larvae of a newly identified type of genus Gnathostoma
      were collected from freshwater eels, Fluta alba, which were purchased at a market
      in Nakhon Nayok, central Thailand. The most remarkable characteristic of the
      newly identified larvae was the larger body size compared with any other larva of
      Gnathostoma spp. They were also distinguishable from other species by the shape
      of their hooklets, which branched in a complex manner at the base: this had not
      been previously observed in any other larval Gnathostoma. The newly described
      larvae had an average number of 44.5, 45.0, 49.0 and 55.1 hooklets on the head
      bulb from the first to the fourth rows, respectively, which were comparable to
      those of larval G. spinigerum. However, the average number of nuclei in each
      intestinal cell was 2.21 and fewer than those of the larvae of G. spinigerum.
      These results suggest that the new type of larvae belong to either G.
      vietnamicum, G. malaysiae, or constitute a new species of the genus Gnathostoma.

PMID- 9139389
TI  - Evaluation of shading of fish farming ponds as a larval control measure against
      Anopheles sundaicus Rodenwaldt (Diptera:Culicidae).
AB  - Larval density of Anopheles sundaicus in shaded and unshaded fish farming ponds
      was monitored at a coastal village in North Sumatra, Indonesia. The average
      density in the experimentally shaded ponds with Nipa leaves was reduced to <
      1/10. Disappearance of algae and decline of water temperature also were observed,
      but the salinity did not change. The larval density was lower in ponds with
      Tilapia sp than without fish, but that in ponds with Ophiocephalus sp was not
      significantly lower. Dominant insects collected by dipping were Agrionidae and
      Libellulidae (Odonata), Corixidae, Notonectidae and Nepidae (Hemiptera), and
      Dytiscidae (Coleoptera). Density of nymphs of both Odonata and Notonectidae was
      higher in unshaded ponds. Taking into account longevity of the materials, and
      easiness in construction and applicability, shading by Nipa leaves was an easy
      and effective larval control measure against A. sundaicus in non-operating small
      fish farming ponds if leaves were renewed once in every two months.

PMID- 9139390
TI  - Rapid and efficient removal of immature Aedes aegypti in metal drums by sweep net
      and modified sweeping method.
AB  - A modified sweeping method was developed using a cotton sweep net for control of
      Ae. aegypti immatures in 200 liter (44 gallon) metal drums which are major
      sources of breeding in Yangon. Laboratory experiments revealed that with only 4
      sweeps (approximately 10 minutes duration), the mean % removal (+/- SD) of Ae.
      aegypti fourth stage larvae was 88.5% +/- 1.47. This was followed by a field
      study undertaken in Sanchaung township, Yangon. Twenty-eight drums with moderate
      (< 500 immatures) to high (> or = 500 immatures) Ae. aegypti density were tested
      in the field. It was found that with only 4 sweeps per drum, a total of 24,886
      immatures were removed out of 29,155 immatures in these 28 drums, giving a mean %
      removal per drum of 85.36% +/- 10.74 (range = 55.54-98.62%). This sweeping method
      is simple, cost-effective, and readily accepted by the community. It could be an
      appropriate technology for control of the dengue hemorrhagic fever (DHF) vector
      Ae. aegypti.

PMID- 9139391
TI  - Age structure of Anopheles subpictus (Diptera:Culicidae) collected by a light
      trap in Halmahela, Indonesia.
AB  - Age structure of Anopheles subpictus Grassi was studied at a Halmahela village,
      Indonesia. Ovary development of females reared with 2% sugar solution after
      emergence ceased at Stage I and their ovary size remained small (mean length x
      width = 0.68 x 0.18 mm). Females with such small ovaries occupied 21.2% of unfed
      Stage I females in cattle-bait samples. The remaining unfed Stage I or II females
      had cleary larger ovaries (mean 1.17 x 0.39 mm). Unfed Stage I or II females
      collected by the outdoor light trap all had large ovaries (mean 1.42 x 0.34 mm)
      irrespective of stages and parity. The parous rate of unfed stage I or II females
      collected by the light trap (86.6%) was significantly higher than that of cattle
      bait samples (69.6%). Feasibility of using outdoor light trapping in malaria
      entomology was discussed.

PMID- 9139392
TI  - Experimental infection of five subspecies of Oncomelania snails with
      Angiostrongylus cantonensis.
AB  - Five subspecies of Oncomelania snails, Oncomelania hupensis nosophora, O.h.
      hupensis, O.h.chiui, O.h.formosana and O.h.quadrasi, were experimentally exposed
      to the first stage larvae of Angiostrongylus cantonesis. The presence of third
      stage larvae was observed in all of the five subspecies of Oncomelania snails 20
      days after infection. Infection rates of the third stage larvae of the parasite
      in Oncomelania snails were 38.0-40.0%. There were no differences in preferences
      among Oncomelania snails. The third stage larvae in Oncomelania snails almost
      distributed in kidney and intestine region, and most of the larvae were active
      and free in tissues. The distribution pattern of the larvae in Oncomelania snails
      was quite different from that in Achatina fulica and Ampullarium sp. These third
      stage larvae were ingested by rats, and developed to adults. These data suggest
      that Oncomelania snails may play important role when A. cantonensis will spread,
      and indicate the possibility of human infection with A. cantonensis.

PMID- 9139393
TI  - Adult respiratory distress syndrome in Thai medical patients.
AB  - Adult respiratory distress syndrome (ARDS) has been a well recognized severe form
      of acute respiratory failure of multiple causes, which is characterized by
      intractable hypoxemia and an extremely high mortality rate. Forty-six cases of
      ARDS admitted to the Department of Medicine, Ramathibodi Hospital during a 39
      months period were studied prospectively to explore the etiologic risk, positive
      end-expiratory pressure (PEEP) profiles, complications and outcome of treatment.
      There were 19 females and 27 males with the mean age of 40 years. Risks of ARDS
      included intra- and extra-pulmonary disease conditions and also tropical diseases
      such as malaria and leptospirosis. At the time of diagnosis, patients in this
      group were extremely hypoxic with a mean arterial/alveolar oxygen tension
      (PaO2/PAO2) of 0.125 +/- 0.04. After the application of appropriate PEEP, the
      mean PaO2/PAO2 ratios increased significantly in both survivor and non-survivor
      groups (0.277 and 0.199). The levels of PEEP used were below 16 and 11 cmH2O in
      93.46% and 67.38% of cases, respectively. Complications of PEEP which included
      barotrauma and hypotension were found in 11 cases (23.9%) with a very high
      mortality rate (81.8%). There were 28 deaths of patients in this study, giving an
      overall 60.8% group mortality rate. Despite the similarities in most clinical
      profiles, the survivors, when compared to the non-survivors, showed a greater
      extent of improved oxygenation in response to the application of PEEP, with fewer
      PEEP complications. The present study would, hopefully, provide the Thai
      clinicians with valuable informations in the management of ARDS.

PMID- 9139394
TI  - The pattern of chronic renal failure in Kelantan, northeastern state of Malaysia.
AB  - The pattern and outcome of patients with chronic renal failure (CRF) in Kelantan,
      the northeastern state of Malaysia was determined. A total of 60 patients with
      CRF managed at the Hospital Universiti Sains Malaysia between January 1991 and
      June 1993 were reviewed retrospectively. The prevalence of CRF was 24.8 patients
      per year. The ratio of male to female patients was 1.5 : 1.0. Their mean age at
      presentation was 51.4 +/- 13.7 years. The cause of CRF in majority of our
      patients was unknown. Their mean blood urea and serum creatinine were 38.9 +/-
      9.8 mmol/l and 1,154.9 +/- 458.7 mumol/l respectively. Sixty-five percent of our
      patients were already in end-stage renal failure (ESRF) at the time of
      presentation and only 53.8% of them could afford a definitive renal replacement
      therapy. Their mortality rate was 21.7% and majority of the death occurred in
      patients who were not receiving definitive renal replacement therapy. This
      debilitating course will continue unless the cost of renal replacement therapy is
      subsidised or a renal transplantation program is activated. Hence public
      education to encourage organ donation in this part of Malysia is necessary.

PMID- 9139395
TI  - Screening proteinuria and hematuria in Malaysian children.
AB  - Screening for proteinuria and hematuria is important in the prevention of chronic
      renal disease. In Malaysia to date no such attempt has been made to establish the
      prevalence of proteinuria and hematuria. A total of 45,149 primary school
      children from three districts in Kelantan were screened for proteinuria and
      hematuria. They were 23,289 boys and 21,860 girls. The prevalence of abnormal
      urinary sediments after third screening was 0.17% ie 0.07% were in boys and 0.10%
      were in girls. The commonest abnormality was proteinuria (0.12%), followed by
      hematuria (0.03%) and combination of proteinuria and hematuria (0.02%). Hematuria
      was more commonly seen in girls compared to boys while proteinuria was seen in
      almost equal proportion in boys and girls. Despite screening large number of
      children the prevalence of asymptomatic proteinuria and hematuria was far lower
      than in an earlier reported study. Furthermore the majority had mild
      abnormalities.

PMID- 9139396
TI  - Parasitic contamination of stored water used for drinking/cooking in Hyderabad.
AB  - A study was undertaken to investigate the parasitic contamination of water in
      Hyderabad city, India. A total of 232 samples of water were collected from
      different places; social welfare hostels, small restaurants, different
      households, public places like railway stations, bus depots, street food vendors,
      hand washings from the food handlers, and vegetable washings from vegetable
      vendors. Of these 232 samples 61 samples indicated the presence of pathogenic
      parasites which include protozoans (cysts of Giardia lamblia, Entamoeba
      histolytica, adult stages of G. lamblia, Balantidium coli) and nematode eggs,
      (Enterobius vermicularis, Ascaris lumbricoides, Trichuris trichiura),
      rhabditiform and filariform larvae and adult stages of Strongyloides stercoralis
      and Enterobius vermicularis. The source of the samples in all places was the
      water stored in overhead tanks and various other containers. Hand washings from
      food handlers also showed the presence of pathogenic parasites although the
      original water used for such washings were free from contamination.

PMID- 9139398
TI  - Microsporidium and Cyclospora in human stools in Chiang Mai, Thailand.

PMID- 9139397
TI  - Disinfection: gaps between recommended and actual practice.
AB  - Basic practices on disinfection was surveyed in 6 hospitals using an observation
      and interview checklist. Two surveys were done, one pre-(first survey) and one
      post-intervention (second survey). The disinfection and sterilization policy of
      the Ministry of Health was not available in 66 (70.2%) and 12 (13%) of the units
      in the first and second survey respectively. In the second survey, staff in all
      the units washed disinfectant containers before refilling compared with 41.5% of
      the units in the first survey. Dilution of disinfectants not recommended was
      found to be used in the first survey. Storing cleaned and sterile items in
      disinfectants, using disinfectant as a substitute for sterilization of
      autoclavable items and not decontaminating spillages were some of the wrong
      practices observed. Considerable improvements were made in the second survey.
      Improper usage of disinfectants was also indicated by failure of the in-use test.
      Rate of failure of disinfectants in-use decreased from 11.6% in the first survey
      to 5.0% in the second survey. To ensure proper disinfection practices, a
      comprehensive training program on disinfection is required for nurses and
      attendants.

PMID- 9139399
TI  - A comparative morphology of Blastocystis hominis cysts with and without the
      "fibrillar layer".

PMID- 9139401
TI  - Brain abscesses due to Geotrichum candidum.

PMID- 9139400
TI  - Streptococcal impetigo among aboriginal children in Malaysia.

PMID- 9139403
TI  - [Headache and facial pain].

PMID- 9139402
TI  - [The patient should tell what is wrong with him. Interview by Klaus Reinhardt].

PMID- 9139404
TI  - [Observations on the history of headache and migraine].

PMID- 9139405
TI  - [Physician and the patient with headache].
AB  - The chronicity of headache, the frequent consultations and the deceiving results
      of most headache treatments characterize the difficult relation of physicians
      with these patients. These particularities are discussed, and some
      recommendations for the relation with headache patients are given.

PMID- 9139406
TI  - [Tension-type headache--diagnosis and therapy].
AB  - According to the classification of the International Headache Society, an
      episodic and a chronic form of tension-type headache are distinguished. In most
      cases the headache is less severe than in migraine patients. For this reason many
      patients never consult their doctor. In the treatment of such patients, one must
      be very cautious with analgesics. There is a considerable risk of chronic use of
      these medications, which may be the cause of a chronic daily headache. Relaxation
      techniques and cognitive training have been shown to be helpful. Most experts
      consider amitriptyline to be the best long-term medication.

PMID- 9139407
TI  - [Migraine--diagnosis, differential diagnosis and therapy].
AB  - Migraine is caused by intermittent brain dysfunction. Attacks result in severe
      unilateral headache with nausea, vomiting, photophobia, phonophobia and general
      weakness. The prevalence of migraine is 12 to 20% in women and 8 to 12% in man.
      Treatment of an acute attack is done by antiemetics in combination with
      analgesics. Severe migraine attacks are treated with ergotamine or sumatriptan.
      Parenteral treatment is performed most efficiently and safely with i.v. ASA.
      Frequent and severe attacks require prophylaxis. Drugs of first choice are
      metoprolol, propranolol, flunarizine and cyclandelate. Substances of second
      choice are valproic acid, DHE, pizotifen, methysergide and magnesium. Homeopathic
      remedies are not superior to placebo. Nonpharmacological treatment consists of
      sport therapy and muscle relaxation techniques.

PMID- 9139408
TI  - [Headache and psyche].
AB  - There exists no 'typical' psychogenic headache. But there is no headache without
      psychogenic component. Preponderance of psychogenesis is given as follows: We
      find it more in permanent undulating headache than in migraine. There are
      psychosomatic bridges via vasomotor functions and cervical spine. In the field of
      triggers, personal biographic psychodynamics, together with the actual situation,
      play a roll. There is a field of modifiers containing depressivity, expertise
      situation and drug abuse. Such psychogenic action on different levels can best be
      perceived via a multifactorial headache concept. This should lead towards a
      multidimensional therapy orientated on target symptoms.

PMID- 9139409
TI  - [The dangerous headache].
AB  - Some particularities are frequent in headache types due to a potentially
      dangerous disease, namely sudden onset, rapid increase of pain intensity, very
      localized headache, increasing frequency and intensity of pain, and the
      insurgence of neurological or psychopathological signs. The headache types
      showing one of these characteristics are discussed in detail.

PMID- 9139411
TI  - [Headache and teeth].
AB  - Headache, facial pain and toothache are poorly localized and irradiate in distant
      areas. Thus, toothache often causes facial pain and headache, but, in turn, it
      can also be mimicked by several forms of these disorders, in particular by a
      myoarthropathy of the masticatory system, a migraine, a tension-type headache, a
      neuropatic pain and a trigeminal neuralgia. The atypical odontalgia is a
      nonodontogenic form of toothache that is difficult to diagnose; therefore, it
      leads to a number of invasive dental procedures which normally worsen the pain
      condition. The atypical odontalgia can often be solely diagnosed by means of a
      diagnostic block. Headache and facial pain can also be caused by a myoarthropathy
      of the masticatory system. This disorder is often misdiagnosed, because the signs
      and symptoms are not pathognomonic, and they are frequently present also in
      healthy individuals. The disorder has a good prognosis, the therapy is generally
      simple and follows the treatment principles for chronic musculoskeletal
      disorders. The burning-mouth syndrome is an other poorly understood form of
      intraoral pain that occurs primarily in postmenopausal females. Several etiologic
      factors have been described, but treatment based on one or more of these factors
      is often ineffective. Spontaneous remission occurs in about half of the patients
      after several years.

PMID- 9139410
TI  - [Trigeminal neuralgia and other facial pain--diagnosis and therapy].
AB  - The hallmark of trigeminal neuralgia is the abrupt onset of short pains in the
      face or in a part of the face, described as stabbing, lightning or electric
      shocks. Attacks are often triggered by cutaneous stimuli to the face or the oral
      cavity, which may be such minor activities as talking, chewing, brushing the
      teeth, or even wind blowing on the face. As a result, facial hygiene as well as a
      good diet may be neglected. Although 1% of the patients may eventually develop
      the disorder bilaterally, pain does not cross the midline during any single
      episode. The clinical course is characterized by exacerbations and remissions,
      but as the disorder progresses, remissions become shorter and exacerbations more
      severe. Carbamazepine is the most powerful drug for this condition, but side
      effects may occur. Neurosurgical treatment may then be considered; the different
      techniques and approaches are mentioned. Other pain conditions in the face will
      be reviewed. If the trigeminal neuralgia may be considered as a nerve irritation,
      like the glossopharyngeal neuralgia and the nasociliary neuralgia, nerve lesion
      may elicit neurogenic or neuropathic pain, characterized by chronic burning pain;
      post-zoster pain, iatrogenic and posttraumatic pain illustrate this condition.
      Cluster headache (Horton neuralgia), Sluder's neuralgia and auriculotemporal
      neuralgia may be related to a dysfunction of the autonomous nervous system.
      Finally, lesion in the mandibular joint may cause unilateral facial pain.

PMID- 9139412
TI  - [Headache in cervical syndrome].
AB  - Headache is a common symptom in patients suffering from cervical spine disorders.
      The percentage of headaches in association with degenerative changes of the
      cervical spine ranges from 13 to 79% and that in association with indirect trauma
      of the cervical spine from 48 to 82%. Based on neuroanatomical and
      neurophysiological studies, the relationship of the upper cervical spine and the
      trigeminal nuclei has been demonstrated and serves as an explanation for
      perceived head pain in cervical spine disorders. As a source of pain, tension in
      the suboccipital muscles, irritation of the third occipital nerve, and
      degenerative changes of the C2/C3 joints have been discussed. Bogduk, in his
      studies, asserts a direct causative role of mechanical derangement of the
      cervical spine in the pathogenesis of cervicogenic headaches. In 1983, Sjaastad
      et al. postulated the concept of 'cervicogenic headaches': a migraine-like
      headache due to certain disorders of the cervical spine, strictly located
      unilaterally, its manifestations being in the temporal, frontal, and ocular
      areas, with associated symptoms such as slight lacrimation, conjunctival
      injections, tinnitus, runny nose, and erythema in the forehead ipsilaterally. As
      arguments in favour of a cervical origin, Sjaastad mentioned the following
      features: precipitation of the headaches either by neck movements or by pressure
      against certain tender spots on the neck, the possibility of homolateral shoulder
      or arm pain, stiffness and pain of the neck, and reduced mobility of the cervical
      spine. In 1988, the Headache Classification Committee of the International
      Headache Society set strict criteria for 'headaches' to be classified as to be of
      cervical origin.

PMID- 9139413
TI  - [Classification of headache].

PMID- 9139414
TI  - [Congenital immune deficiency diseases].

PMID- 9139415
TI  - [Science needs experimental animals].
AB  - Data on the number of animals used in experiments are compared with data on meat
      consumption. The usefulness of laboratory animals for past achievements in
      biological sciences is presented. The negative effect of the rather disapproving
      attitude of the general public and the restrictive Animal Protection Law on
      Germany as a place of science is demonstrated in the general decrease of the
      number of registrated scientific projects. Some psychological reasons for the
      widespread disapproval of animal experiments are listed. The arguments of the
      opponents and supporters of animal experiments are confronted. Finally, the
      limits of so-called alternative methods are briefly mentioned and some proposals
      to ameliorate the keeping conditions of laboratory animals are enumerated.

PMID- 9139416
TI  - [Possibilities and limitations of drugs to protect the liver].
AB  - In this paper preventive liver protective agents for the prophylaxis of
      hepatopathies due to functional stress, and curative protective agents for
      therapy of existing liver damage are distinguished. Preventive liver protective
      agents are key substances in the metabolism of proteins, carbohydrates, lipids,
      and sulfur. For curative liver protective agents, inhibitors of RNA and protein
      synthesis, calcium antagonists and inhibitors of sulfhydryl (-SH) containing
      enzymes are proposed and substantiated.

PMID- 9139417
TI  - [Preparation of a realistic calf model for obstetrical instruction].
AB  - Construction of a largely realistic and flexible calf-dummy for the instruction
      and practice of veterinary obstetrical procedures is described. The most
      important steps are presented in detail and illustrated by means of figures. The
      fundamental materials include: threaded rods, artificial metal joints, hard foam
      with a coating of soft foam rubber for neck and trunk, a flexible metal tube
      filled with silicone to imitate the vertebral column and silicone acetate
      injected into moulds to form the limb segments and the head. The natural skin,
      which had been specially tanned in order to retain its elasticity, was sewed over
      the flexible dummy. Adherence to the original proportions and a realistic
      replication of the limb joints ensured that the flexibility and movement of the
      dummy approaches that of an original calf.

PMID- 9139418
TI  - [Stone age deerfly (Lipoptena cervi) found with a mummy in a glacier].
AB  - In hair samples from the accompanying equipment of a human mummy preserved in
      glacial ice in South Tyrol for more than 5000 years, numerous remains of insects
      were found. These fragments corresponded in form, size and structural
      organization to the features of the deer ked, Lipoptena cervi. Considering the
      biology and ecology of L. cervi with regard to the finding place of the mummy at
      an altitude of 3210 m above sea level in a glacier it is concluded that the deer
      keds invaded the equipment before and not after the death of the Stone Age man.

PMID- 9139419
TI  - [The clinical case. Female dog, Shar-pei, 11 months old].

PMID- 9139420
TI  - [Chylothorax in a calf].
AB  - A case of chylothorax caused by fracture of thoracal vertebrae in a two-day-old
      Swiss Braunvieh male calf ist described. The clinical symptoms were those of a
      unilateral, progressive pleural effusion. This was confirmed by radiological and
      ultrasonographic examinations. Thoracocentesis was performed under
      ultrasonographic assistance. The liquid obtained from the pleural cavity was
      turbid and contained chylomicrons, lymphocytes and neutrophilic granulocytes as
      well as a high concentration of triglycerides. These qualities go together with
      chylus. Immunohistological examination for BVD virus turned out to be positive.
      An intrauterine disturbance of osteogenesis due to BVD virus must be considered a
      possible cause for fracture of vertebrae during delivery.

PMID- 9139421
TI  - [Ultrasonic pregnancy diagnosis (B-mode) in sheep. 2. Comparative studies using
      transcutaneous and transrectal pregnancy diagnosis].
AB  - The aim of this study was to check the earliest time for the ultrasonic pregnancy
      diagnosis in flock management of sheep after finishing the mating season.
      Therefore a transcutaneous pregnancy diagnosis (5 MHz) took place on a total of
      1060 German merino-mutton sheep between day 10 and 90 after mating (a.m.) and a
      transrectal diagnosis (5 MHz) took place on a total of 1442 German merino-mutton
      sheep between day 10 and 70 a.m. At the beginning of the third week a.m. the
      accuracy of transrectal diagnosis was over 95% and increased to 100% on day 35
      a.m. At that time the accuracy of transcutaneous diagnosis was 80% and reached
      100% on day 60 a.m. Considering the reached accuracies the pregnancy diagnosis
      should not take place before day 35 after the end of the breeding season. After
      day 35 a.m. it is advisable to combine the transcutaneous and the transrectal
      pregnancy diagnosis. That means that at first all animals are examined by
      transcutaneous sonography and in the second step the so-called "non-pregnant
      sheep" are checked by transrectal ultrasound. From the beginning of the third
      month a.m. a single transcutaneous pregnancy diagnosis is sufficient.

PMID- 9139422
TI  - [Immunopathology of Borna disease in the horse: clinical, virological and
      neuropathologic findings].
AB  - Tissues from nine horses and one donkey suffering from natural Borna disease were
      investigated. Clinically, all animals demonstrated progressive reduced mentation
      and aggravating gait disturbances. During the clinical course anorexia and
      progressive loss of proprioception were observed. Cranial nerve failure was
      accompanied by signs of pharyngeal paralysis, sialorrhea, bruxism, and by
      blindness. Virologically, infectious virus was detected in the brain of all
      animals investigated but was not found regularly in all areas of the brain.
      However, in all cases, infectivity was found in the thalamus and the hippocampal
      area. In contrast, in other compartments of the central nervous system virus was
      not detected regularly. These findings correlate well to the results obtained
      from assaying Borna virus-specific RNA by Reverse Transcriptase-Polymerase Chain
      Reaction (RT-PCR) and virus specific antigen by immunohistochemistry. No evidence
      of infection was found in the autonomic nervous system and peripheral organs.
      Immunomorphologically, lymphocytic inflammatory reactions and increased
      expressions of MHC class I and class II antigen were found in the brain as well
      as in the trigeminal and olfactory system. No evidence of inflammation was found
      in the retina. From the finding that BDV-proteins and nucleic acids were even
      more abundant in the trigeminal system as compared to the olfactory system, we
      conclude that infection may have occurred via the trigeminal nerve.

PMID- 9139423
TI  - [The effect of the season and sexual stress on the concentration of testosterone
      and estradiol-17beta in the seminal plasma of stallions].
AB  - Semen from three stallions was collected weekly for six months (December through
      May) to determine semen parameters and hormones (testosterone and estradiol-17
      beta) in seminal plasma. Once a month three ejaculates were collected at
      intervals of one hour and examined accordingly. Testosterone and estradiol-17
      beta were also determined in peripheral blood plasma (V. jugularis) collected
      twice a week. Semen parameters (volume, gel-free volume and sperm concentration)
      were clearly influenced by season. The testosterone concentration in peripheral
      blood plasma was lowest during December whereas in seminal plasma testosterone
      concentration gradually increased throughout the experimental period.
      Testosterone concentrations in seminal plasma were only one tenth of those in
      peripheral blood. Estradiol-17 beta in blood plasma was highest in April and May
      whereas no significant differences occurred in seminal plasma. Average monthly
      concentrations of estradiol-17 beta in blood and seminal plasma were in the range
      of 27.4 pg/ml to 45.3 pg/ml. Collection of three successive ejaculations led to a
      significant decrease of ejaculate volume as well as sperm concentration.
      Ejaculation frequency did not influence testosterone in seminal plasma whereas
      the concentration of estradiol-17 beta decreased significantly in the second and
      third ejaculate. The results indicate that estradiol-17 beta in the stallion's
      semen may be bound to spermatozoa or is accumulated in seminal plasma.

PMID- 9139424
TI  - [The use of the veterinary cuttable plate in 160 cases].
AB  - The use of the Veterinary Cuttable Plate (VCP) is described using the experience
      in 160 cases. The range of its use and the technique of application is shown in
      cats and small, medium sized and large dogs, and complications are discussed.

PMID- 9139425
TI  - [Maintenance of the cranial cruciate ligament rupture in the dog using an intra
      articular ("over-the-top") and an extra-articular ("fascia-doubling") method].
AB  - The present study compares the results of an intraarticular ("over-the-top") and
      an extraarticular (fascia lata imbrication) surgical method to treat the rupture
      of the cranial cruciate ligament in dogs. In a period of 18 months, 132 stifle
      joints of 125 dogs with a partial or complete rupture of the cranial cruciate
      ligament were examined according to a systematic protocol at the Clinic for Small
      Animals of the Hannover School of Veterinary Medicine, Hannover, Germany. Surgery
      was performed with either one or the other of the two surgical techniques. In all
      cases a " cleaning up " was carried out. If the medial meniscus was damaged, it
      was resected and the lesion was investigated. The imbrication technique of the
      lateral aspect of the fascia lata was easier and faster to perform. Using the
      "over-the-top" method, there were difficulties to guide the fascial strip through
      the intercondylar notch. After six months 88 patients were re-examined clinically
      and radiologically according to the same protocol as mentioned above. In the
      present study it was demonstrated that patients treated with the extraarticular
      method showed a higher rate (76.5%) of normal limb function after six months and
      walked earlier without lameness compared with dogs operated with the "over-the
      top" technique (41.5%). The same results were valid for patients of giant breeds.
      Patients operated with the imbrication technique showed more arthrosis of the
      patellar tip. After six months stability, evaluated with the cranial drawer test
      and the tibia compression test was satisfying with both techniques.

PMID- 9139426
TI  - [Dorsal recumbency in dogs--a circulatory risk during surgical treatment?].
AB  - In this study, changes in hemodynamic, blood gas, and metabolic variables
      recorded during right lateral and dorsal recumbency in beagles anaesthetised with
      thiopental are presented. Other than reported in human beings, dorsal recumbency
      in these dogs resulted in an increase (33%) in heart rate, decrease (30%) in
      systolic, diastolic, and mean systemic arterial pressure, a decrease (17%) in
      systemic vascular resistance, and a decrease in both right (31%) and left (39%)
      ventricular work in comparison with lateral recumbency. Furthermore, mixed-venous
      PO2, oxygen saturation and respiratory quotient were lower in dorsal than in
      lateral recumbency while O2 consumption and lipolysis were increased in the
      former. The changes presented may have been caused by beta-adrenergic stimulation
      in dorsal recumbency. It needs to be studied if capillary perfusion can be
      maintained adequately during surgery in dorsal recumbency or if this predisposes
      to cardiovascular shock.

PMID- 9139427
TI  - [Anesthesia in domestic animals (small mammals, psittacines and reptiles)].
AB  - The presentation of small animals and exotic pets (birds, reptiles) in veterinary
      practice is increasing. Physiological and ethological variations demand specific
      precautions in restraining/ anesthetizing these patients. In Psittacines
      hypoglycemia, hypoxia and hypothermia are typical side-effects. Long-acting
      recovery control in birds and reptiles is necessary.

PMID- 9139428
TI  - [Isoflurane anesthesia in rabbits in a closed anesthetic system].
AB  - Using the Stephens anaesthetic apparatus-which is a closed system with an in
      circuit, nonprecision vaporizer-and isoflurane as anaesthetic gas, 18 rabbits
      were anaesthetized and showed sufficient hypnosis, analgesia, and muscle
      relaxation during bone surgery. Induction of anaesthesia was achieved with
      intravenous propofol and all rabbits were intubated afterwards. During the
      following isoflurane inhalation anaesthesia the mean arterial blood pressure
      decreased considerably (compared to control measures before induction), the heart
      rate remained the same or showed a slight increase, and the respiratory rate
      decreased. The arterial pO2 decreased corresponding to the respiratory depression
      after propofol induction and increased again during spontaneous ventilation with
      100% oxygen. The changes in arterial pCO2 and pH were representative for a rise
      in the CO2-stimulation threshold. A moderate metabolic acidosis could be seen due
      to preanaesthetic excitement of the animals. Recovery time was short (between one
      and 11 minutes) and no signs of excitation could be detected. The consumed volume
      of isoflurane was 0.80 ml/kg BW/h.

PMID- 9139429
TI  - [Age-dependence of laboratory values in dogs and cats. III. Bilirubin, creatinine
      and proteins in serum].
AB  - Serum creatinine and protein are age dependent in the dog as well as in the cat.
      The differences require consideration of special reference values in young
      animals. In contrast, the mean value of serum bilirubin shows only a slight, but
      significant dependency on age in dogs, which is not of diagnostic importance.

PMID- 9139430
TI  - [The determination of von Willebrand factor activity in the plasma of dogs. 1.
      Experimental evaluation and methods].
AB  - Using a new aggregometer, the plasma activity of von Willebrand factor (vWF) in
      dogs was measured. The method is described. It has the advantage of being more
      precisely for the diagnosis of von Willebrand's disease than the determination of
      von Willebrand antigen (vWF: Ag) by using an ELISA. With the method described
      reproducible and reliable result can be obtained.

PMID- 9139431
TI  - Proceedings of the 5th Pan American Symposium on Animal, Plant and Microbial
      Toxins. Frederick, Maryland, USA, 30 July-4 August 1995.

PMID- 9139432
TI  - [Karyometry of the tumor epitheliocytes in the dysplastic sections of serous
      tumors and in serous cancers of the ovaries].
AB  - With the help of Integral-2MT cytoanalyzer, the average area of nuclei and the
      percentage of epitheliocytes with small, medium and large nuclei at the site of
      dysplasia of serous cysts and serous ovarian carcinomas have been evaluated. An
      increase in the degree of dysplasia of tumorous epithelium is associated with an
      increase in the average area of nuclei and the number of cells with medium
      nuclei. A decrease in the degree of differentiation of serous ovarian carcinomas
      is accompanied by increasing percentage of cells with large nuclei. Preoperative
      chemotherapy does not affect this regularity.

PMID- 9139433
TI  - [Cell division as the determining factor in the index of the proliferative level
      of cultured cells].
AB  - Theoretical substantiation of dynamics of cultured cell average size as a basis
      for the index of rate of their proliferative activity in population is presented.
      Mathematic formula deduced by the author for this index is described. Some
      examples for its use are given and the name for the index is proposed.

PMID- 9139434
TI  - [A cytofluorometric study of the stability of secondary DNA structure in the
      epithelial cells in endometrial hyperplasia and cancer].
AB  - Studies were performed on epithelial cells obtained from uterine cavity in 49
      women. All cases were subdivided into four groups; unaltered endometrium-9,
      glandular endometrial hyperplasia-10, atypical hyperplasia-4 and endometrial
      adenocarcinoma-30. For fluorimetric evaluation of single- and double-strand DNA
      specimens were dyed with acridine orange, which is known to produce red
      fluorescence in combination with double-strand acids. Values of coefficients
      alpha for single and double-strand DNA after acid hydrolysis were much higher
      than those before acid treatment. This study provides a deeper insight into the
      relation between DNA lesions and malignancy.

PMID- 9139435
TI  - [The 30th anniversary of the journal Tsitologiia i genetika].

PMID- 9139436
TI  - [The genetic polymorphism of the grape studied by RAPD analysis].
AB  - Genetic polymorphism in plant of 3 genera of Vitaceae family, 11 species of Vitis
      genera, 10 cultivars of Vitis vinifera and 4 cultivars that obtained from distant
      hybridization was studied. According to date of RAPD analysis genetic distances
      were determined and phylogenetic dendrogram was constructed. The possibility of
      using PCR for evaluation of breeding material by the levels of genetic relations
      was shown.

PMID- 9139437
TI  - [The status of the progeny of male rats subjected to low-dose external gamma
      irradiation exposure].
AB  - In studies on 120 mature males of Wistar rats and 252 female rats of the same
      line, 20-day-old fetuses and 974 young rats of the first generation, anomalies of
      antenatal and postnatal development were found after exposure of spermatids and
      spermatozoa to gamma-radiation in doses 0.25-1.0 Gy. After exposure of male rats
      to radiation in dose 0.25 Gy, reliable delay of pelvic bone ossification was
      observed as compared to the control.

PMID- 9139439
TI  - [The genetic differentiation of sheep with different types of wool].
AB  - The comparative analysis of the genetic structure of fine-wool, semi-fine-wool,
      and semi-rough-wool sheep breeds for 8 polymorphous genetic-biochemical systems
      (Hb, LDR, PN, ME, EST, Dp, Tf, LAP) was carried out. The interbreed, breed and
      intrabreed differentiations by the polymorphism for genetic-biochemical systems
      were described. The interrelations between the variability of wool
      characteristics and the genetic structure of ME and Tf loci, repeated in
      different sheep groups, were revealed. The "linkage disequilibrium" between ME
      and Tf loci was detected. The possible mechanisms of the involvement of
      polymorphous genetic-biochemical systems into selection processes based on the
      complex of important economical traits were discussed.

PMID- 9139438
TI  - [The antimutagenic action of apiculture products].
AB  - Using the battery of test-systems, we studied the possible antimutagenic activity
      of some products of apiculture. It is established that apilak-preparation made on
      the basis of queen bee milk didn't show gene-protective abilities in Ames test.
      The rest products of apiculture: propolis, beebread, honey preparations N1 and
      N2, and queen bee milk manifested to some degree their ability to decrease the
      mutagenic effects of some chemical and physical mutagens. The toxic effect of
      propolis upon yeast cells was established. Queen bee milk manifested the least
      antimutagenic properties (on all test-objects used in experiments).

PMID- 9139440
TI  - [The dermatoglyphics of patients with different forms of tuberculosis of the
      respiratory organs].
AB  - The dermatoglyphic studies showing the existence of genetic predisposition to the
      development of lung tuberculosis were conducted. Comparison of dermatoglyphs of
      patients with various forms of tuberculosis has shown their significant
      coincidence. A hypothesis about similar character of predisposition to all forms
      of lung tuberculosis is suggested.

PMID- 9139441
TI  - [The prevalence of diabetes mellitus in children of different regions of
      Ukraine].
AB  - Prevalence of diabetes mellitus among the children of Ukraine increased by 7%
      during the period from 1985 to 1992. The incidence that are revealed each year
      does not change. Different regions are significantly distinct from each other.
      The high and stable level of this disease incidence in Cherkassy Province,
      including cases revealed for the first time, two times exceeds these indices for
      Ukraine that attracts considerable interest.

PMID- 9139442
TI  - [A statistical genetic analysis of the calving traits of cows of a Ukrainian beef
      breed].
AB  - The results of investigation of calving features in 371 cows of Ukrainian beef
      cattle were summarized. Variance and correlation analyses of factors affecting
      calving in cows were used. Breeds, pedigrees of parents and progeny, assessment
      of complicated and lethal calvings, duration of pregnancies and mass of newborns
      were registered. The influence of selection type on the normal calving was shown.

PMID- 9139443
TI  - [The methodological aspects of assessing the mutagenic background and genetic
      risk for man and the biota from the action of mutagenic ecological factors].
AB  - Methodology of the assessment of territory state for mutagenic background and
      genetic risk was proposed. It is based on analysis of results of cytogenetic
      monitoring of high-sensitive bioindicators and children populations as well as an
      analysis of statistic data on hereditary and ecology-dependent diseases in human
      populations. Methodology has been tested under the conditions of Dnepropetrovsk
      Province, that allowed to specify areas of increased genetic risk.

PMID- 9139444
TI  - [The ultrastructure of the chromaffin cells of the adrenal medullary substance in
      different forms of pheochromocytoma].
AB  - The ultrastructure of adrenal medullar pheochromocytoma cells has no specific
      features, although these cells are characterized by morphological signs of high
      functional activity. Secretory granules of pheochromocytoma cells have variable
      morphology and electron density. Granule content is released from cells by
      diffusion or exocytosis. The structure of adrenocytes and noradrenocytes has
      features which allow to distinguish cell types from each other.

PMID- 9139445
TI  - Certified herds scheme. British Veterinary Association.

PMID- 9139446
TI  - Proposed reorganization of the Veterinary Field Service.

PMID- 9139447
TI  - Legislation on sheep scab.

PMID- 9139448
TI  - [Are all animal and human organs and tissues endocrine in nature and are they
      secreting peptide hormones into blood?].
AB  - Endocrinology was born and developed as the science of endocrine glands and the
      human and animal diseases induced by the gland dysfunctions. The complex of
      endocrine glands included pituitary, thyroid and parathyroid glands, adrenals,
      pancreas and gonads. Further, it has been shown that certain brain structures,
      hypothalamus in particular, are also endocrine organs which secrete in blood a
      large number of various peptide hormones. Heart secretes in blood the peptide
      compound natriuretic hormone which regulates the sodium balance. Recent studies
      have been demonstrated that the adipose tissue cells adipocytes secrete in blood
      the peptide hormone leptine which stimulates utilization of lipids from the fat
      deposits in energy metabolism. Leptine is the product obese (ob) gene which is
      mainly expressed in white adipose tissue. The first natural compound named
      "hormone" was the peptide "secretin". It is secreted by not a traditional
      endocrine gland, but by the duodenal cells, and it controls the exosecretory
      function of the pancreas. The trend allows us to declare that, similarly to
      adipose tissue, heart and hypothalamus, all other human and animal tissues are
      probably also endocrine organs and able to secret in blood the peptide hormones
      still to be identified, which being informative polymers are better adapted to
      transmit the information than other chemical compounds, and hence, they are most
      efficient for regulatory functions.

PMID- 9139449
TI  - [Receptor mechanisms of glucocorticoid and antiglucocorticoid effects].
AB  - An analysis of receptor mechanisms of glucocorticoid and antiglucocorticoid
      effect was made. The limiting link in glucocorticoid and antiglucocorticoid
      realization are specific cytoplasmic glucocorticoid receptors (GR) which function
      is controlled by heat shock protein (HSP) of 90 kD molecular weight. Under the
      influence of glucocorticoids (G), GR are released from GR-HSP complex, forming GR
      G complexes. The latter are translocated into cell nucleus activate the function
      of genetic apparatus, change biosynthesis of specific enzymes realizing
      intracellular glucocorticoid effect Receptor mechanism of antiglucocorticoid
      effect is realized via competition of steroid and non-steroid drugs with
      glucocorticoids for binding sites on GR or pharmacological stabilization of GR
      HSP complex, decreasing 4SGR release, 4S GR-G forming, and 4SGR-G translocation
      into cell nucleus. New data about GR chemical structure according to which GR
      contain 3 functional domains, characterized by regulatory DNA-binding and ligand
      binding activity promote researches of antiglucocorticoids. It promoted synthesis
      of a new most active receptor antiglucocorticoid RU-486 (19-norsteroid), that
      inhibits ovalbumin and conalbumin synthesis induced by glucocorticoids.

PMID- 9139450
TI  - [Ability of carbon dioxide to inhibit generation of superoxide anion radical in
      cells and its biomedical role].
AB  - The study was carried out on blood phagocytes and alveolar macrophages of 96
      persons, cells of inner organs and tissue phagocytes (liver, brain, myocardium,
      lungs, kidneys, stomach, skeletal muscles), as well as on mitochondria of the
      liver of 186 non-linear white mice. Generation of active oxygen forms (AOF) was
      evaluated by various methods with CO2 directly affecting the cells and bioptates
      and indirectly the whole organism. The results show that CO2 with tension close
      to that of the blood (37.0 mm Hg) and at higher tensions (60 and 146 mm Hg) is a
      powerful inhibitor of AOF generation by human and animal cells, as well as by
      liver mitochondria of mice. The data obtained allow to explain, in terms of AOF
      role, a number of physiological and pathophysiological (medical) CO2 effects.

PMID- 9139451
TI  - [Modification of cytochrome P-450 apoenzyme during its oxidative self
      inactivation in a reconstituted mono-oxygenase system].
AB  - The hemoprotein self-inactivation is accompanied by oxidation of all-groups,
      carbonyl group formation, changes in aggregate state and apoenzyme
      polymerization. It is probable that heme loss and oxidative modification of
      apoenzyme is a important step in regulation of P450 decay in cell.

PMID- 9139452
TI  - [Mechanism of relationship between HIV infection and autoimmunity].
AB  - The mechanism of autoimmunity suppression of T-lymphocytes with 18K-antigen as
      marker of autoimmunopathology developments was investigated. Mushroom,s L-lysine
      alpha-oxidase was used as immunomodulator. It was suggested that the development,
      of the first stage autoimmunity pathology may be realized via overproductive
      synthesis of cell proteins required for HIV reproduction.

PMID- 9139453
TI  - [Experimental study of the effect of formaldehyde during embryogenesis on the
      activity of rat liver enzyme systems in ontogenesis].
AB  - The pregnant rats were treated with formaldehyde (0.5 mg/kg daily per os) during
      whole period of pregnancy. The activity of cytochrome-c-oxidase, malate
      dehydrogenase, nucleotidase, glucose-6-phosphatase, beta-glucuronidase, N-acetyl
      beta-glucosaminidase, beta-galactosidase, H(+)-ATPase, glutamate dehydrogenase,
      NAD- and NADP-isocitrate dehydrogenase, fructose-bisphosphate aldolase, glucose-6
      phosphate dehydrogenase and content of protein in liver celts of offsprings
      (newborns, 2 weeks age and 2 months age) were studied. It was shown differences
      in development enzyme systems of control and experimental animals during
      ontogenesis.

PMID- 9139455
TI  - [Various biochemical indices of wound healing during treatment with preparation
      SK].
AB  - There was investigated that the change of isoenzyme spectrum of
      laktatdegidrogenaze (LDG) in the dynamic of rats skin wounds healing, and also
      the activity of some antioxidative enzymes and the accumulation of one lipid
      peroxidation product (LJO). It was discovered that the enzyme spectrum LDG was
      reconstructed faster with treated animals by SK preparation. The phase of
      antioxidative enzymes activity and accumulation of some LFO products were
      recognized. SQ, the increasing of the katalaza activity in group, where the SK
      was used.

PMID- 9139454
TI  - [Functional characteristics of fructose-2,6-bisphosphate system in the liver
      during experimental streptozotocin diabetes].
AB  - The activity of phosphofructokinase-2, fructose, 1,6-bisphosphatase, glucokinase,
      and also the level of fructose 2,6-bisphosphate and glycogen were examined in the
      liver of normal, and streptozotocin-diabetic rats. It was shown that the activity
      of phosphofructokinase-2 was decreased in the liver of diabetic rats. Besides
      that the activity determined at pH 6.6 (the "active" or unphosphorylated enzyme
      form) was 3-fold reduced whereas the "total" enzyme activity as measured at pH
      8.5 was lowered 1,7-fold. The phosphofructokinase-2 activity assay at two pH
      values allows to estimate a degree of phosphorylation of bifunctional enzyme
      which is markedly enhanced in diabetes. The fall of the bifunctional enzyme k in
      case activity is accompanied by the lowered fructose 2.6-bisphosphate level,
      increased fructose 1,6-bisphosphatase activity that in turn favours the liver
      tissue glycolysis inhibition and gluconeogenesis enhanced in diabetes.

PMID- 9139456
TI  - [Ultracytochemical study of activity of various phosphatases during early
      postmortem period in experimental animals].
AB  - The activities of acid phosphatase (AP), glucose-6-phosphatase (G-6-P), and
      thiamine pyrophosphatase (TPP) were assayed in the epithelial cells of the main
      bronchi and hepatocytes of rats within 1 to 5 hours after their death. In the
      postmortem period, some enzymes (AC, G-6-P) retained their activity while the
      others (TPP) were inhibited. Furthermore, there were unusual intracellular sites
      of AP reaction products.

PMID- 9139457
TI  - [Comparison of biological activity of high molecular weight and low molecular
      weight forms of immunoreactive prolactin from human serum in cultured lymphoma
      NB2 cells].
AB  - In experiments with NB2 rat lymphoma cells culture sensitive to lactogenic
      hormones the mitogenic activity of high molecular weight (> OOK) immunoreactive
      prolactin, found in substantial quantities in serum of certain hyperprolactinemic
      women, as compared to the activity of serum low molecular weight (23K) form, was
      studied. It was established that the ratio of immunoreactive to biologically
      active prolactin content in serums in cases of low molecular weight form
      predominance is close to 1,0 whereas in case of predominant content of high
      molecular weight form it is substantially higher (1.5-2.3), apparently because of
      low biological activity of high molecular weight form. Direct comparison of
      mitogenic effects of equivalent quantities of serum immunoreactive prolactin
      forms with high and low molecular weight, separated by gel-filtration, confirmed
      low biological activity of high molecular weight form. Monoclonal antibodies to
      prolactin completely suppressed mitogenic activity of low molecular weight form
      and only partially--high molecular weight one. The data obtained indicate that
      high and low molecular weight forms of human serum immunoreactive prolactin
      differ in their biochemical and functional characteristics. Therefore their ratio
      in the circulating blood can substantially affect the clinical manifestations of
      hyperprolactinemia.

PMID- 9139459
TI  - [Physico-chemical properties of pulmonary surfactant after gastrectomy and
      cholecystectomy].
AB  - The frequency of broncho-pulmonary complication after the surgery in the organs
      of upper part of the abdominal cavity does not decrease, although the technique
      of operation and methods of anaesthesia have been improved. Disorders in the
      functioning of the surfactant systems of the lungs are evident in patients with
      chronic gastric and duodenal ulcers and calculous cholecystitis. Surgical
      intervention and anaesthesiologic measures promote further disturbance of the
      functional activity of lung surfactants. The most pronounced disorders in the
      functioning of the surfactant systems of the lungs were observed in patients with
      the broncho-pulmonary complications, commonly on the third day after the
      operation. This condition, is one of the main pathogenic causes of the
      manifestation of broncho-pulmonary complications in the post-operative period.

PMID- 9139458
TI  - [Comparative study of collagen in hypertrophic and keloid cicatrix].
AB  - The relative percentage of type III to type I collagen, the ratio of alpha 1(I)
      to alpha 2(I) collagen chains and the ratio of dimers (beta-chains) to monomers
      (alpha-chains) in type I collagen have been measured in solubilized collagen
      fractions from keloids and hypertrophic scars aged about 1-7 years after burn. In
      tissue samples the content of crosslink with structure of pyridinoline were
      analyzed and expressed as mole of crosslink per mole of collagen. A comparison
      between hypertrophic and keloid scars has shown that the young (about 1 year)
      hypertrophic scars have higher ratios alpha 1(I)/alpha 2(I) and beta 11 + beta
      12/alpha 1(I) + alpha 2(I). The increased proportion of beta-chains in the
      younger hypertrophic scars approximated to the same level as in normal skin
      within 7 years after lesion. There was no decrease in the ratio dimers/monomers
      of collagen type I with age of keloid scar tissue. The relative amount of
      collagen type III in young keloid scars was found decreased as compared to age
      matched hypertrophic scars (13 +/- 3 and 17 +/- 7 respectively), but was similar
      in the older scars. The average pyridinoline crosslinks content per mole of
      collagen in keloids was 2 times as high as in hypertrophic scars. The data
      support the suggestion that general, as well as peculiar disturbances of collagen
      metabolism are involved in the development of keloids and hypertrophic scars.

PMID- 9139460
TI  - [Ceramides and gangliosides in benign and malignant human ovarian tumors].
AB  - Composition and content of ceramides and gangliosides from different kinds of
      human ovary benign and malignant epithelial tumours were studied. The ceramide
      content was shown to decrease significantly in the tumours, especially in
      malignant tumours, in comparison with the normal ovary tissue. In the tumour
      ceramides a sphingosine base composition changes: sphinganine was found along
      with sphingenine, which is characteristic for normal ceramides. The fatty acid
      composition changes also. Main tumour gangliosides were shown to be GM3 and GD3.
      Their content decreases in malignant ovary tumours, especially the amount of
      ganglioside GD3. As a result of these changes the molar ratio Cer/Sia decreases.
      It can appears stimulates a tumour growth.

PMID- 9139461
TI  - [Beta amyloid in blood and cerebrospinal fluid is associated with high density
      lipoproteins].
AB  - Cerebrovascular and parenchymal amyloid deposits found in brains of Alzheimer's
      disease, Down's syndrome and normal aging are mainly composed of aggregated
      amyloid beta protein (A beta), a unique peptide 39 to 44 amino acids long. A
      similar but soluble A beta (s A beta) has been identified in plasma,
      cerebrospinal fluid (CSF) and cell supernatants, indicating that it is a normal
      protein. We report here that s A beta in normal human plasma and CSF is complexed
      to high density lipoprotein (HDL) 3 and very high density lipoprotein (VHDL).
      Biotinylated synthetic peptide A beta 1-40 was traced in normal human plasma in
      in vitro experiments. Both tracer biotin-labeled A beta 1-40 and native s A beta
      were specifically recovered in HDL3 and VHDL as it was assessed in
      immunoprecipitation experiments of purified plasma lipoproteins and lipoprotein
      depleted plasma. This fact prompted us to ascertain whether the interaction of s
      A beta with HDL does occur in normal human CSF in vivo. For this purpose normals
      human CSF was fractionated by means of sequential flotation ultracentrifugation.
      The presence of s A beta in the resulting lipoprotein fractions as well as in the
      lipoprotein depleted CSF was analysed by immunoblot analysis, electron and immune
      electron microscopy and native size exclusion chromatography. Immunoblot analysis
      with 6E10 monoclonal anti-A beta antibodies revealed s A beta association with
      all HDL subspecies of CSF, primarily HDL3 and VHDL and immunoelectron microscopy
      confirmed an association of s A beta with CSF-HDL particles of 16.8 + 3.2 nm.
      Native size exclusion chromatography followed by immunoblot analysis with
      antibodies against A beta and different apoliproproteins indicated an association
      of s A beta with HDL complexes of approximately 200 kDa molecular weight. Soluble
      A beta association with HDL3 and VHDL may be involved in maintaining the
      solubility of A beta in biological fluids and points to a possible role of
      lipoproteins and lipoprotein lipid in the biology of aminoloidogenic peptides.

PMID- 9139462
TI  - [Endorphins and neurotensin in Huntington chorea].
AB  - Concentration of alpha-endorphin, beta-endorphin, gamma-endorphin and neurotensin
      in blood and beta-endorphin in cerebrospinal fluid of 48 patients with various
      forms of Huntington's disease was measured. Two modifications of immunoassay were
      used. The level of all neuropeptides studied was significantly decreased.
      Patients with a kinetiko-rigid form of the disease showed a two-fold lowering in
      beta-endorphin levels in cerebrospinal fluid in comparison with patients with the
      classic form. The relationships between these findings and clinical-biochemical
      characteristics of Huntington's disease are discussed.

PMID- 9139463
TI  - [New aspects in diagnosis and therapy of hereditary diseases of the nervous and
      skeletal systems].

PMID- 9139464
TI  - [Enzyme replacement therapy: a new treatment concept in Gaucher disease].
AB  - Until recently the treatment of lysosomal storage disorders was entirely
      supportive. A new enzyme replacement therapy has become available in Gaucher's
      disease, a lipid storage disorder that is due to a genetic defect of beta
      glucocerebrosidase. Intravenous infusions of modified beta-glucocerebrosidase has
      produced clinical improvement in Gaucher patients, with regression of
      organomegaly and increase in blood counts. At the Children's Hospital of Mainz 13
      patients (6 children and 7 adults) were treated with alglucerase on a high-dosage
      regimen (60 units per kilogram every two weeks). A decrease in liver and spleen
      size was observed 4 to 6 months after commencement of therapy. Hemoglobin and the
      number of platelets increased. In some cases, a reduction of the dosage was
      possible after a year of enzyme replacement-therapy. A growth spurt was observed
      in the children. The availability of enzyme replacement therapy is limited by its
      high cost; however, in the future gene transfer may become the treatment of
      choice.

PMID- 9139465
TI  - [The Austrian Metabolic Register].
AB  - The "Austrian Register for Metabolic Disorders" was founded in 1995 on the
      initiative of the "Work Group for Congenital Metabolic Disorders" within the
      Austrian Society for Pediatrics. It is designed as a clearinghouse for reporting
      and recording congenital metabolic disorders and aims to determine the frequency
      and regional distribution of these diseases. Another objective is to have patient
      data handy if and when new therapeutic options or new means of diagnostic
      verification, including carrier status or prenatal diagnosis, become available.
      Currently more than 400 patients are on record with disorders of amino acid,
      organic acid, lipid or carbohydrate metabolism, as well as disorders of the
      mitochondria, peroxisomes and lysosomes; furthermore, dyschromia, porphyria and
      diseases of connective tissue and disturbances in the metabolism of purines,
      pyrimidines, metals or vitamins. Lysosomal enzyme defects, mitochondrial and
      peroxisomal disorders account for the majority of cases. Patients have to be
      reported on a continuous basis as prerequisite for this initiative to be
      successful. It is, therefore, planned to incorporate reporting of metabolic
      disorders to the "Register" on a national scale as integral part of the diagnosis
      of these conditions.

PMID- 9139466
TI  - [Diagnosis and therapy of mitochondriopathies].
AB  - Defects of the mitochondrial energy production cab be expressed in many tissues
      and may lead to various types of diseases. Since defects can occur on many sites
      of the oxidative phosphorylation system, molecular diagnosis can be difficult. In
      typical mitochondrial syndromes, like MELAS- or MERRF-syndrome, diagnosis can be
      suspected already on clinical grounds. Lactate measured in various body fluids is
      still the best selective screening parameter. Loading tests, respectively
      ergometry is only necessary in the milder clinical forms of diseases or possibly
      in older children. The in vivo lactate determination e.g. In the CNS by 1H NMR
      spectroscopy can be helpful in evaluating prognosis. The diagnosis of a
      mitochondriopathy is usually confirmed enzymatically by tissue biopsies; skeletal
      muscle is still the tissue of the first choice because some enzyme deficiencies
      are not sufficiently expressed in cultured fibroblasts. If possible, intact
      mitochondria should be investigated polarografically along with histology and
      histochemistry. Finally several parts of the respiratory chain and pyruvate
      dehydrogenase complex are analyzed by single enzyme measurement. Also combined
      deficiencies have been described. Polypeptide subunits of respiratory chain
      complexes can be investigated by means of immunoblotting. The investigations of
      the mitochondrial DNA from the end of the diagnostic scale. The application of
      various new therapeutic agents, such as antioxidants, radical scavangers and
      cofactors have not come to any persuasive clinical result. But there is a number
      of reports about some successful treatment with coenzyme Q10, vitamin K3, vitamin
      C, riboflavin, thiamine, dichloroacetate and in PDHC -deficiency with ketogenic
      diet. Mitochondrial gene therapy appears only theoretical and speculative.
      Because of the enormous heterogeneity even on the DNA-level genetic counselling
      is reserved for some cases with exact molecular diagnosis.

PMID- 9139467
TI  - [Clinical neuroepidemiology: the science of medical expertise in neurology].

PMID- 9139468
TI  - [Descriptive epidemiology of cerebrovascular disorders in Austria].
AB  - The trend of cerebrovascular mortality (ICD-9: 530-538) is analyzed. Age
      standardized mortality rates for men and women were calculated, covering the the
      period 1970 to 1994. Furthermore, the development of mortality rates (1974 to
      1994) was analyzed for age groups and birth cohorts (5-years intervals). The
      number of deaths has decreased, from a total of 14,734 in 1970 (6109 men, 8625
      women) to 9917 (-32%) in 1994 (men 3541, -42%; women 6376, -26%); age
      standardized death rates in men from 201.4/10(5) (-54.7%) to 91.9/10(5), in women
      160/10(5) to 77/10(5) (-51.7%). The trend within individual age groups does not
      show any sex-specific differences. In all birth cohorts the mortality trend in
      men and women decreases towards younger age groups. The observed linear decrease
      of mortality in men and women towards younger age groups leads to the assumption
      that this trend is determined by decreasing incidence, indicating a secular
      trend. This trend may only be explained but by its risk reducing effect in both,
      men and women of any age group. Establishing a representative stroke register
      seems most desirable, in order to make possible assertions as to the trend of
      incidence and prevalence.

PMID- 9139469
TI  - [Stroke prevention with a high risk strategy of treating hypertension in patients
      after a transient ischemic attack].
AB  - High-risk strategies represent important preventive measures that focus on
      individuals with a defined high risk of suffering a chronic disease. They are
      valuable in addition to measures of prevention within the general population. One
      example for a high-risk approach for stroke prevention is the treatment of
      hypertension in individuals that have previously suffered a transient ischemic
      attack (TIA). Data from the Klosterneuburg Stroke Data Bank and other sources
      enable an estimate of 2000 TIAs occurring in Austria each year, half of them
      being hypertensives that are mostly not treated or not sufficiently treated for
      their hypertension. A high-risk programme that implies forced and effective
      treatment of hypertension would prevent some 400 strokes or 3% of 16,000 first
      ever strokes per year. Costs for preventing one stroke by means of Betablocker
      agents would amount to ATS 3500 and by ACE-inhibitor agents ATS 11,500,
      respectively. In addition to general preventive measures, such a programme would
      have an important impact on stroke incidence and public health.

PMID- 9139470
TI  - [Prevalence and risk factors in the population of Graz (Austrian Stroke
      Prevention Study)].
AB  - The Austrian Stroke Prevention Study recruited 1960 randomly selected subjects
      aged 50 to 75 years during a 3-year period of enrollment. The response rate of
      the study was 32.4%. A telephone interview with 200 randomly selected non
      responders yielded no differences to responders regarding the frequency of major
      vascular risk factors known to the subjects. Besides demographics, the study
      assessed arterial hypertension, diabetes mellitus, cardiac disease, smoking, a
      complete lipid status including the apolipoprotein-E genotype, serum fibrinogen
      and anticardiolipin antibodies as well as various natural antioxidants such as
      vitamins A, C, E and beta-carotene. Arterial hypertension, diabetes mellitus,
      cardiac disease and hypercholesterolemia > 200 mg/dl were strikingly common and
      occurred in 38%, 7.6%, 32% and 76%, respectively. Suboptimal plasma
      concentrations of vitamin A, E, and beta-carotene were noted in 77.2%, 56.1% and
      in 53.2% of study participants. The rate of treatment of major risk factors known
      to the subjects prior to study entry were 60.3% and 70% for arterial hypertension
      and diabetes mellitus, but only 37.1% and 6.3% for cardiac disease and
      hypercholesterolemia > 250 mg/dl. Diet was commonly used to treat diabetes but
      was almost neglected in the treatment of other vascular risk factors. These data
      provide an orientation on the prevalence of risk factors and the use of primary
      preventive measures for stroke treatment in our community.

PMID- 9139471
TI  - [Modification of risk factors after cerebral infarct: results of the
      Klosterneuburg Stroke Databank].
AB  - A number of studies have shown that reduction of elevated blood pressure and
      other major risk factors are essential for the primary prevention of stroke. In
      contrast, only sparce data exist as to the reduction of risk factors in secondary
      prevention although many patients are only ready to modify their lifestyle after
      having suffered a stroke. This study reports the results of the one-year follow
      up examinations from the Klosterneuburg Stroke Data Bank, a prospective, hospital
      based registry. Out of 870 stroke survivors (97.4% follow-up rate) registered
      between 1988 and 1994 575 patients (69%) had been hypertensive before their index
      stroke. Out of these, 112 hypertensives (19.7% of all hypertensives) had not
      received antihypertensive treatment before their index stroke. Compared to all
      other hypertensive stroke patients they were significantly younger (p = 0.01),
      more often regular drinkers (p = 0.01), and regular smokers (p = 0.007). They
      showed significantly less heart diseases (p = 0.03) as well as prior strokes (p =
      0.006). 12 months after the index-stroke the rate of untreated hypertension in
      this group fell to 6.0% (34 patients). In the latter group there were more
      frequent prior strokes compared to those hypertensives who started regular
      treatment after their index stroke (p = 0.003). Out of 221 smokers only 115 (52%)
      had quit smoking within one year after the index-stroke and 110 out of 270
      (40.7%) stroke patients that had had regular alcohol intake had stopped drinking.
      42 out of 118 (36%) patients who had been regular drinkers and smokers continued
      to drink and smoke. Regular intake of aspirin was noted more often in those
      patients who also had regular blood pressure checks (p = 0.009) and regular
      antihypertensive treatment (p = 0.001). It is concluded that there is
      insufficient modification of risk factors after stroke and controlled
      interventional studies in secondary stroke prevention are an important issue.

PMID- 9139472
TI  - [Embolism in left-atrial thrombi (ELAT Study): are spontaneous echo contrast,
      thrombi in the left atrium/appendage and size of the left atrial appendage
      predictors of possible embolisms?].
AB  - Transesophageal echocardiography visualizes the left atrium, the left atrial
      appendage, thrombi and spontaneous echo contrast within them. The role of these
      findings as predictors for embolism in atrial fibrillation is unknown. We
      performed transesophageal echocardiography in 409 non-rheumatic atrial
      fibrillation outpatients (62 +/- 12 years, 36% female) with no recent (< 1 year)
      history of embolism. Patients with left atrial/appendage thrombi received oral
      anticoagulation, those without thrombi Aspirin. The patients were followed up
      over 2 years. Primary events were stroke, embolism and non stroke/embolism
      related deaths. Secondary events were initiation of anticoagulation in patients
      primarily assigned to Aspirin. Left atrial/appendage thrombi were diagnosed in
      2.5%. They were associated with diabetes, heart failure and decreased left
      ventricular fractional shortening (p < 0.05 for each variable). Spontaneous echo
      contrast was diagnosed in 12%. It was associated with increased age, constant
      atrial fibrillation, hypertension, heart failure, valvular abnormalities and
      increased left atrial diameter (p < 0.05 for each variable). Increased left
      atrial appendage size was associated with constant atrial fibrillation, etiology
      of atrial fibrillation and valvular abnormalities (p < 0.05 for each variable).
      Follow-up was 25 +/- 7 months. 29 patients suffered a stroke, 33 further patients
      died of non stroke/embolism related causes. Secondary events occurred in 19
      patients. Neither left atrial/appendage thrombi nor left atrial appendage size
      were predictors for embolism. Predictors for embolism were increased age (p =
      0.003), hypertension (p = 0.01) and increased diastolic blood pressure (p =
      0.04). In non-rheumatic atrial fibrillation outpatients with no recent history of
      embolism, transesophageal echocardiography is of limited value to assess embolic
      risk. Hypertension and increased diastolic blood pressure have been confirmed in
      their significance as clinical predictors for embolism.

PMID- 9139473
TI  - [Nikolai Aleksandrovich Bernshtein (on the centenary of his birth)].

PMID- 9139475
TI  - [The structure and connections of the basal ganglia. The striatum].
AB  - On the base of personal studies there were reviewed contemporary data about the
      internal organization of mammal striatum (n. caudatus, putamen): of their
      histological and histochemical differentiation, neuronal content, mediators of
      their neurons, and of the intrinsic and extrinsic connections of these structural
      elements: there were put forward some hypothesis about functional specificity of
      these elements and about the arrangement of striatal neuronal network.

PMID- 9139474
TI  - [The mechanisms of the integrative activity of neurons].
AB  - Modern state of neuron integrative activity problem was considered at the base of
      data analysis received during investigations of simple learning forms in molluscs
      and long-term potentiation in mammalians. Experimental data shown that different
      forms of synaptic plasticity which have been characterized by common or
      particular features of molecular providing involved in integrative activity of
      various kinds of nervous cells during some forms of learning. Mechanisms of
      postsynaptic messengment convergated to exiting neurons and there molecular
      transformation in cytoplasm and nuclei were discussed. Hypothesis of long-term
      synaptic plastic transformation and detention mechanisms in snail neurons during
      associative learning was suggested.

PMID- 9139476
TI  - [The role of the novel hypothalamic peptide PACAP in regulating endocrine
      functions].
AB  - During last ten years in the hypothalamus various neuropeptides have been
      identified. These peptides play the role of neurotransmitters, neuromodulators,
      neurohormones, regulator substances in neuroendocrine neurones etc. The last
      discovery of a novel neuropeptide was determined by experimental results
      suggested that the ovine hypothalamus contains an unknown substance, which
      simulated adenylate cyclase level in the pituitary cells culture. This substance
      is a novel 38 acid peptide named as pituitary adenylate cyclase activating
      polypeptide (PACAP). Recently PACAP complementary DNA has been cloned in human
      and some species of mammals. Besides the localization of PACAP-synthetizing
      neurones have described in the mammalian brain. Moreover PACAP was detected in
      the hypophysial and general circulation. Since the information about PACAP has
      not published in Russia. So far the review is dedicated to analyzing of foreign
      literature as well author's own data on biochemistry, molecular biology,
      neuroanatomy and physiology of PACAP-synthetizing structures in the hypothalamo
      hypophysial neuroendocrine complex.

PMID- 9139477
TI  - [The functional role of nitric oxide in the central nervous system].
AB  - The article is dedicated to the role of free-radical gas nitric oxide (NO) in the
      central nervous system. The paper gives the review of literature data related to
      the distribution of NO-synthesizing neurones in the CNS of mammals, to the role
      of NO in the control of the activity of central neurones and to the involvement
      of this messenger in the central autonomic regulation.

PMID- 9139478
TI  - [The molecular physiology of the adrenergic receptors].

PMID- 9139479
TI  - [The role of the opioid system in body adaptation and protection of the heart in
      stress].
AB  - Literary data and the results of our own studies on the role of opioid
      neuropeptides in the adaptation of organism and heart protection under the action
      of extreme factors were analysed. The data on the cardioprotective,
      antiarrhythmic, neurohumoral, antistressor effects of enkephalins are grown.
      Possible mechanisms and the role of various populations of opiate receptors in
      the realisation of opioid peptides' adaptation effects are studied. The key role
      of endogenous opiate system in the mechanism of cardioprotective effects of
      natural adaptogens and adaptation is established.

PMID- 9139480
TI  - [Memory disorders due to extreme exposures and their pharmacological correction].
AB  - The review contains the present-day data on new neurophysiological and
      neurochemical mechanisms of learning and memory processes disturbances induced by
      such extreme factors as microwaves, hypoxia [correction of hyghproxia], motion
      sickness, electro-convulsive shock, etc. The main attention is concentrated on
      the role of some nootropic drugs in preventing the memory-impairing effect of all
      these extreme factors. The current concept of the mechanisms action of the
      nootropics in these extreme conditions is discussed.

PMID- 9139481
TI  - Options for the control of influenza III. Cairns, North Queensland, Australia (4
      9 May 1996).

PMID- 9139482
TI  - Adjuvants--a classification and review of their modes of action.
AB  - Since early this century, various substances have been added to vaccines and
      certain formulations have been devised in an attempt to render vaccines more
      effective. Despite a plethora of options, only aluminium salts have gained
      acceptance as human vaccine adjuvants and even veterinary vaccines are largely
      dependent upon the use of aluminium salts. Currently, many new vaccines are under
      development and there is a desire to simplify vaccination schedules both by
      increasing the number of components per vaccine and decreasing the number of
      doses required for a vaccine course. New, more effective adjuvants will be
      required to achieve this.

PMID- 9139483
TI  - Immunization of mice with poliovirus replicons expressing the C-fragment of
      tetanus toxin protects against lethal challenge with tetanus toxin.
AB  - In this study, we describe the construction of poliovirus genomes or "replicons"
      which contain the C fragment gene of tetanus toxin substituted for the poliovirus
      P1 capsid. Upon transfection of replicon RNA into cells, we immunoprecipitated a
      protein corresponding to the C-fragment of tetanus toxin using tetanus-specific
      antibodies. Using a recombinant vaccinia virus expressing poliovirus P1 capsid
      protein (VV-P1) to provide P1 protein, the replicon RNA was encapsidated; stocks
      of the replicons were generated by passage with VV-P1. The immunogenicity of the
      replicons was determined by immunization of transgenic mice which are susceptible
      to poliovirus. A serum antibody response to poliovirus and tetanus toxoid was
      detected in all of the immunized mice. Protection against a lethal dose of
      tetanus toxin generally correlated with the levels of serum anti-tetanus
      antibodies. To address whether pre-existing antibodies to poliovirus limit the
      effectiveness of the replicon as a vaccine vector, mice were first immunized with
      the inactivated poliovirus vaccine followed by immunization with the replicons
      expressing C-fragment protein. Anti-tetanus antibodies were detected in these
      mice after a single administration of the replicon; these antibodies conferred
      protection upon challenge with tetanus toxin. These results demonstrate the
      potential use of poliovirus replicons encoding foreign proteins to induce a
      protective antibody response, even in the presence of pre-existing antibodies to
      poliovirus.

PMID- 9139484
TI  - Eliciting HIV-1 envelope-specific antibodies with mixed vaccinia virus
      recombinants.
AB  - Recombinant vaccinia virus (VV) vectors that express the envelope (Env) protein
      of the human immunodeficiency virus-type 1 (HIV-1) have been previously shown to
      elicit HIV-specific cytotoxic T-lymphocyte (CTL) and weak antibody responses in
      non-human primate studies and clinical trials. In first clinical trials, single
      Env proteins were presented to the immune system by VV recombinants and other
      vectors, but individuals were not protected against later exposures to
      heterologous HIV. It is likely that the generation of protective immune responses
      against diverse HIV will require that vaccines encompass proteins from not just
      one, but multiple distinct HIV isolates. Here is described the simple
      construction of numerous new VV, each expressing a unique, truncated, Env protein
      (VVenv). Mouse experiments were performed to evaluate the ability of these VVenv
      to elicit immune responses. HIV-1-specific antibodies appeared within one month
      following one intraperitoneal inoculation of mice with single or mixed VVenv,
      reaching plateau levels by 4 months. The magnitude of antibody production was
      poor at the dose of 10(5) p.f.u. VVenv per animal, but improved with increasing
      doses of VVenv up to 10(7) p.f.u. per animal. The subcutaneous route of VV
      immunization, previously proven safe in human trials, was also effective for
      administering VVenv. These results highlight the strengths of recombinant VV
      constructs as vehicles for the presentation of multiple HIV-1-Env proteins to the
      naive immune system.

PMID- 9139485
TI  - Immunogenicity of a low-passage, high-titer modified live canine parvovirus
      vaccine in pups with maternally derived antibodies.
AB  - The study evaluated the ability of a low-passage, high-titer modified live canine
      parvovirus (CPV) vaccine to produce seroconversion in pups with maternally
      derived hemagglutination inhibition (HI) titers ranging from < 8 to < or = 256.
      The vaccine's low-passage CPV strain was less attenuated and therefore more
      infective than conventional modified live CPV strains in order to overcome
      relatively greater levels of maternally derived antibodies, the principal cause
      of CPV vaccine failures in pups. To assess vaccine performance under field
      conditions, healthy pups presented at five private veterinary clinics were used
      as test animals. A single dose of vaccine was given to 59 pups at 12 weeks of age
      (Group A). To accommodate the protocol of clinics where earlier CPV vaccination
      was practiced, 87 other pups were vaccinated with two doses, the first at 8-10
      weeks of age, and the second at 12 weeks of age (Group B). Geometric mean HI
      titers were measured for blood samples obtained at the time of vaccination and at
      14 weeks of age. Seroconversion was considered to have occurred if pups developed
      a fourfold or greater increase in HI titer to a level > or = 64. Of the 59 pups
      in Group A, 100% seroconverted following the single vaccine dose at 12 weeks of
      age. Of the 87 Group B pups, 82 (94.3%) seroconverted following either of the two
      vaccine doses. A geometric mean HI titer of 4828 was measured for Group A, and a
      geometric mean HI titer of 2028 was measured for Group B. An overall
      seroconversion rate of 96.5% was achieved in pups with maternally derived HI
      titers < or = 256.

PMID- 9139486
TI  - Red blood cells as delivery system for recombinant HSV-1 glycoprotein B:
      immunogenicity and protection in mice.
AB  - The immunotherapeutic potential of autologous red blood cells (RBC) coupled to
      the secretory form of herpes simplex virus type 1 (HSV-1) glycoprotein B (gB1s)
      was examined with a mouse model of HSV-1 infection. C57BL/6 mice were immunized
      intraperitoneally with gB1s (0.05 microgram per dose) linked to RBC, or mixed
      with Freund's complete or bound to AlPO4 adjuvants (0.5 microgram per dose). Mice
      immunized with RBC coupled gB1s were protected against lethal and latent HSV-1
      infection, and developed an anti-HSV antibody response, as measured by ELISA and
      HSV-1 neutralization assays, similar or higher than that elicited by the same
      antigen in Freund's complete adjuvant, which suggested that autologous RBC
      coupled to gB1s may provide an effective and safe method of immunization against
      HSV infection.

PMID- 9139488
TI  - The influence of maternal immunity on the transmission of pseudorabies virus and
      on the effectiveness of vaccination.
AB  - The purpose of this study was to investigate whether maternal immunity could
      prevent transmission of pseudorabies virus (PRV) among pigs, and whether it
      reduced the effectiveness of a single or double vaccination with regard to the
      transmission of PRV. In five experiments, the transmission of PRV, expressed as
      the reproduction ratio R, was compared in groups of pigs with maternal immunity
      and in groups of pigs without maternal immunity. Transmission of PRV among
      unvaccinated pigs with maternal immunity (R = 0.2) was significantly lower than
      among pigs without maternal immunity (R = 6.3). Furthermore, maternal immunity in
      young pigs prevented transmission of PRV, as R was significantly below one. In
      once-vaccinated groups, PRV spread extensively among pigs with maternal immunity
      (R = 23), but did not spread extensively among pigs without maternal immunity (R
      = 0.6). In twice-vaccinated groups, transmission of PRV among pigs with maternal
      immunity (R = 0.6) did not differ significantly from the transmission of PRV
      among pigs without maternal immunity (R = 0.3). Thus, a single vaccination of
      pigs with PRV strain 783 at 10 weeks of age, when they still possessed maternal
      immunity, seemed not sufficient to prevent transmission of PRV. Virus
      transmission could be reduced, however, if maternally immune pigs were vaccinated
      twice at 10 and 14 weeks of age.

PMID- 9139487
TI  - Particulate vaccine candidate for Japanese encephalitis induces long-lasting
      virus-specific memory T lymphocytes in mice.
AB  - We previously reported that extracellular particles (EPs) composed of premembrane
      (prM) and envelope (E) proteins were released from cells infected with
      recombinant vaccinia viruses encoding Japanese encephalitis (JE) virus prM and E
      genes. In the present study, EPs were evaluated for induction of JE virus
      specific antibody and specific T lymphocytes in mice. Six- to 8-week-old male
      Balb/c mice were inoculated intraperitoneally once or twice (at a 3-week
      interval) with purified EPs containing 1 microgram of E without adjuvant.
      Neutralizing antibody was detected and spleen cells proliferated against JE viral
      antigen 3 weeks after the second immunization with EPs. Neutralizing antibody and
      JE virus-specific T lymphocytes were also detected 10 months after immunization
      with EPs containing 2 micrograms of E. Spleen cells obtained from EP-immunized
      mice and stimulated in vitro with live JE virus, expressed JE virus-specific
      cytotoxic activity. The cytotoxic activity was reduced by treatment with anti-CD3
      antibody and complement. These results indicate that immunization with EPs
      induces long-lasting specific antibody and memory T cells in mice.

PMID- 9139489
TI  - Safety and immunogenicity of an acellular pertussis diphtheria tetanus vaccine
      given as a single injection with Haemophilus influenzae b conjugate vaccine.
AB  - To determine if an acellular pertussis-diphtheria-tetanus vaccine could be
      combined with a Haemophilus influenzae b conjugate vaccine as a single injection,
      we randomized 468 children between 17 and 21 months of age previously immunized
      with three doses of each vaccine to receive a five-component acellular pertussis
      vaccine combined with diphtheria and tetanus toxoids, and Haemophilus influenzae
      b-tetanus toxoid conjugate vaccine either as separate injections on separate
      days, separate injections on the same day, or as a single combined injection.
      Rates of adverse reactions were similar amongst the groups except for increased
      injection site tenderness (29.2% vs 17%, RR 1.76, 95% CI 1.09-2.85) and fussiness
      (36.4% vs 23.3%, RR 1.59, 95% CI 1.05-2.41) in the group given the combined
      injection rather than separate injections on separate days. Antibody levels
      against the capsular polysaccharide of H. influenzae b after the single combined
      injection (47.1 micrograms ml-1) were lower than after separate injections on the
      same day (66.0 micrograms ml-1; P < 0.05) but higher than when the injections
      were administered on separate days (28.4 micrograms ml-1; P < 0.001). We conclude
      that the five-component acellular pertussis vaccine is safe and immunogenic when
      combined with diphtheria and tetanus toxoids and H. influenzae b-tetanus toxoid
      conjugate vaccine in children receiving the fourth dose of the immunization
      series.

PMID- 9139490
TI  - Estimates of the effectiveness of a whole-cell pertussis vaccine from an outbreak
      in an immunized population.
AB  - Pertussis has re-emerged as a public health problem in Canada in recent years,
      emphasizing concerns about the effectiveness of the currently licensed whole-cell
      vaccine. Following a 1994 outbreak in Nova Scotia, we conducted a case-control
      study of 483 children aged < 10 years to assess vaccine effectiveness. Ninety
      three percent of children aged 6 months and above had received three or more
      doses of vaccine, however, only 78% had received age-appropriate immunization.
      Among children aged 4 years and more, vaccine effectiveness against laboratory
      confirmed pertussis was 57% (95% CI, 23-77%) for age-appropriate immunization
      (five doses) vs partial or no immunization. Vaccine effectiveness increased with
      increasing number of doses from 25% (95% CI, -58-65%) for three or more doses to
      55% (95% CI, -15-83%) for five doses, compared with 0-2 doses.

PMID- 9139491
TI  - Intranasal booster vaccination against diphtheria and tetanus in man.
AB  - The booster responses of three different formulations of intranasal (i.n.)
      diphtheria-tetanus (D-T) vaccines were determined in military recruits and
      compared with a conventional subcutaneous D-T vaccine. The vaccines for mucosal
      delivery were sprayed into one nostril and contained D and T toxoids in an
      enhancer mixture of polysorbate and caprylic/capric glycerides. All of the
      vaccines gave rise mainly to a systemic IgG response. Among 51 persons with anti
      D antibody concentrations in serum below a protective level of 0.01 international
      units (IU ml-1) before vaccination, all except two attained protective antibody
      concentrations 4 weeks after vaccination. The median increase in anti-D antibody
      concentration was 113-fold with the most efficient i.n. formulation. The median
      increase in anti-T antibody level was 2.4-fold, however, the pre-vaccination
      levels for this antigen were very high. Within the examined levels, the booster
      response depended mainly on the dose of the antigen in the vaccine rather than on
      the concentration of the vehicle mixture. Compared with the parenteral D-T
      vaccine containing aluminium hydroxide as an adjuvant, all of the tested i.n.
      formulations showed somewhat lower immunogenicity in man as well as in pre
      clinical guinea-pig studies. Among 215 persons immunized i.n., 61% preferred this
      route of administration rather than a parenteral injection, although the
      formulations were all associated with varying local symptoms, frequently stinging
      and pronounced, nasal secretion.

PMID- 9139492
TI  - The impact of vaccination strategy and methods of information on influenza and
      pneumococcal vaccination coverage in the elderly population.
AB  - We compared the coverage achieved with either an age-based, free-of-charge
      vaccination program offering influenza vaccine alone or with pneumococcal vaccine
      with a restricted risk disease-based influenza vaccination program supplemented
      by self-funded immunization. We also compared two means of informing the public,
      either using mailed personal reminders or through the mass media only. Forty-one
      administrative districts with a total of 41,500 persons aged 65 years or older
      participated in the study during three consecutive seasons from 1992 to 1994. The
      average vaccination coverage achieved by the risk disease-based program was 20%,
      by the age-based program with mass media information, 52%, and by the age-based
      program with mailed personal reminders 82%. The availability of free-of-charge
      vaccines is thus not sufficient to ensure a high vaccination rate. The effect of
      the personal reminders was restricted to the year they were sent. The addition of
      pneumococcal vaccine to the age-based influenza vaccination program had little
      influence on the acceptance rate.

PMID- 9139493
TI  - In a vaccine model, selected substitution of a highly stimulatory T cell epitope
      of hen's egg lysozyme into a Salmonella flagellin does not result in a
      homologous, specific, cellular immune response and may alter the way in which the
      total antigen is processed.
AB  - A 13 amino acid peptide corresponding to a potent BALB/c mouse T cell epitope of
      hen's egg lysozyme (HEL) was substituted singly at five sites in the d flagellin
      of Salmonella muenchen. The resulting chimeric proteins were unable to expand T
      cells capable of being stimulated by the HEL epitope and induced T cell
      populations which either failed to respond or responded at a low level to a
      normally highly stimulatory flagellin T cell epitope that was present in all
      chimeras. The results suggested that substitution of a T cell epitope in
      flagellin may alter the processing of the resulting immunogen.

PMID- 9139494
TI  - Factors associated with superior antibody responses to a single dose of
      Haemophilus influenzae type b-tetanus toxoid conjugate vaccine administered to
      Chilean infants at 2 months of age.
AB  - The anticapsular antibody response of Chilean infants to a single dose of
      Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugate,
      vaccine is substantially higher than that observed among infants of similar age
      from the USA. Comparison of selected demographic and environmental factors
      indicates that low maternal education and a greater number of persons in the home
      are significantly associated with the superior responder phenotype. High
      anticapsular antibody responses were associated with high antibody responses to
      tetanus toxoid, the carrier protein in this conjugate, but not to diphtheria
      toxoid. These data suggest that environmental factors may enhance the magnitude
      of the primary antibody response to PRP-T vaccine.

PMID- 9139495
TI  - Measles vaccination of Thai infants by intranasal and subcutaneous routes:
      possible interference from respiratory infections.
AB  - Reactogenicity and seroresponses were studied after standard doses of Edmonston
      Zagreb measles vaccine were given intranasally (i.n.) and subcutaneously (s.c.)
      to 6-month-old Thai children. Few children given i.n. vaccine (2/31), but most
      (13/21) given s.c. vaccine, seroconverted. All but 1 of 51 children were
      seropositive after receiving vaccine s.c. at 9 months-of-age. Upper respiratory
      infection (URI) outbreaks with onsets in the week following vaccination occurred
      after each vaccination session and were equally common in all groups. URIs
      following i.n. vaccination at 6 months may have adversely affected response to
      i.n. vaccine, while URIs after s.c. vaccination at 9 months adversely affected
      final geometric mean antibody titers. I.n. measles vaccination does not appear to
      be an acceptable route for routine vaccination.

PMID- 9139497
TI  - [Friedrich Rumpf and his contributions to modern gynecologic surgery].
AB  - The German gynecologist Friedrich Rumpf from Berlin performed the first radical
      hysterectomy in Europe. This pioneering achievement is even more remarkable as
      Rumpf was working in private practice without the support of one of the major
      Berlin university hospitals. Very few biographical data can be found.
      Fortunately, his views of gynecologic surgery are expressed in his publications.
      This aim of this article is to remind us of Rumpf's reflections on surgical
      technique which are still relevant today and to contribute to Rumpf's memory.

PMID- 9139496
TI  - Replication and immunogenicity of Ad7-, Ad4-, and Ad5-hepatitis B virus surface
      antigen recombinants, with or without a portion of E3 region, in chimpanzees.
AB  - Human adenovirus vectors containing intact or largely deleted E3 region were used
      to construct adenovirus-hepatitis B recombinant viruses (Ad-HepB) and shown to
      produce substantial amount of recombinant protein, hepatitis B surface antigen
      (HBsAg), in tissue culture. Previously we showed that these viruses were able to
      elicit good anti-HBs antibodies in a dog model. In the present study, the Ad-HepB
      viruses were evaluated for replication and immunogenicity in chimpanzees which
      sustain permissive infection by human adenoviruses. Recombinants containing
      entire E3 region showed better replication pattern than their E3 deleted
      counterparts as evidenced by longer duration and high titers of virus shedding.
      The effect of E3 region was also seen in the antibody titers against HBsAg in
      that the E3 containing viruses showed better response than the E3 deleted
      viruses. The importance of E3 region for the development of adenovirus vectored
      vaccines is further discussed.

PMID- 9139498
TI  - [Incidence of inflammatory placental changes in threatened premature labor with
      and without additional antibiotic therapy].
AB  - Considering the causal association of silent intrauterine infection and
      prematurity we investigated the possible effect of adjuvant antibiotic treatment
      of women with preterm labour on the appearance of inflammatory placental lesions.
      140 patients with preterm labour in the 30 + 2 week of gestation (median; range:
      17 + 2-34 + 6) without premature rupture of the membranes and detection of
      facultative-pathogenic micro-organisms in the vagina and/or in the canal of the
      cervix were enrolled in the study. 74 women were treated vaginally (polyvidone
      iodine) in addition to intravenous tocolysis, 66 women were given ampicillin,
      cefotiam or erythromycin intravenously. After delivery the placentas were
      examined histologically and the frequency of inflammatory lesions was evaluated
      by use of 4 scores of classification. For statistical analysis the Fisher Exact-
      and the Wilcoxon Rank Sum Test were used. We found no differences concerning
      amnamnestic and perinatal parameters comparing the 2 groups of patients. With
      only one of the histological scores used (according to Salafia et al. [18]) we
      found a higher frequency of inflammatory placental lesion in the antibiotic
      treated group (12/66) in comparison to the vaginal treated group (4/74). Fifty
      patients of the antibiotics' group received the antibiotic during the last 10
      days before birth. No differences in the frequency of inflammatory placental
      lesions were detectable in these patients when compared with the local treated
      group. However, we found a lower prolongation of gestation (calculated from the
      day of admission to the day of delivery, median: 7; range: 1-92 days) and a lower
      gestational age at delivery (median: 33 + 0; range: 22 + 2-39 + 6 weeks) in the
      patients receiving antibiotics during the last 10 days before birth in comparison
      to the local treated women (22; 1-138 days and 35 + 0; 23 + 4-41 + 5 weeks,
      respectively). There is the same incidence of inflammatory placental lesions in
      patients with preterm labour and facultative-pathogenic micro-organisms in the
      vagina and/or in the canal of the cervix who received adjuvant antibiotic
      treatment during pregnancy compared with patients who were treated vaginally with
      polyvidone-iodine.

PMID- 9139499
TI  - [Color Doppler ultrasound of uterine, fetoplacental and fetal blood vessels in
      the 2nd trimester in normal pregnancies].
AB  - We investigated 69 healthy women with normal pregnancy and delivery in order to
      establish normal values for the second trimester of gestation. In a cross
      sectional study we measured the pulsatility index (PI), the maximal systolic
      velocity (V-MAX) and the mean velocity (V-MEAN) in the uterine arteries (UAA),
      the umbilical artery (UA), the fetal thoracic aorta (FTA) and the middle cerebral
      artery (MCA) from the 14th to the 24th week of gestation. A regression analysis
      shows a significant slope of the PI of UAA and UA (p < 0.01), whereas in contrast
      to the UA there is no significant difference of the median values of the UAA-PI
      from the 18th week of gestation. With progressive gestation V-MEAN of UAA
      increases more (p < 0.001) than V-MAX (p < 0.05) as a result of the increasing
      diastolic blood flow. In the UA there is also a significant rising trend of V-MAX
      and V-MEAN (p < 0.0001). No significant changes of the PI of FTA and MCA are
      seen, although there is a slight increasing trend. After the 20th week in the MCA
      a marked tendency to high PI-values is observed, whereas there is a change
      between different flowpatterns prior to the 20th week. V-MAX and V-MEAN of FTA
      increases significantly, but there is no change in the MCA. Our results for UAA
      and UA correspond to the known morphologic changes in the utero- and
      fetoplacental vessels in the second trimester and are comparable to other
      results. Particularly the physiology of the cerebral perfusion needs to be
      investigated more intensively. These normal values provide a good basis for early
      and complex assessment of a disturbed perfusion in the second trimester.

PMID- 9139500
TI  - [Differential diagnosis of cystic adnexa processes. A comparison of the value of
      sonography, puncture cytology and color and biochemical biopsy analysis with
      histology].
AB  - The histological diagnoses of 109 cystic adnexal masses were compared with the
      results of ultrasound examination, color, cytology and biochemical analyses of
      cystic fluid. In cases with suspicious results by ultrasound examination most of
      the malignant tumors but only a small number of benign cystic masses were found.
      Macroscopic and cytologic examinations gave no further informations. By
      biochemical analyses functional cysts could be detected with 86% of sensitivity
      and 100% of specificity by a combination of estradiol, progesterone and Ca 12-5.
      Endometrioma and malignant tumors could be separated from other adnexal masses
      (specificity 95%, sensitivity 100%) with a combination of Tag 72-4 and CASA.

PMID- 9139501
TI  - [Ultrasound and clinical studies of periventricular leukomalacia in high risk
      newborn infants. I. Neuro-ultrasound results].
AB  - The incidence of periventricular leukomalacia (PVL) in risk neonates was
      evaluated in a prospective ultrasound study at the Pediatric Hospital of the
      Medical Faculty, University of Rostock. The study was carried out in 300
      registered risk neonates. These risk neonates were divided into 3 groups: < or =
      31 gestational week (n = 70), 32-36 gestational week (n = 154), > or = 37
      gestational week (n = 76). A prenatal PVL was diagnosed in 41 neonates, a
      postnatal PVL was found in 56 neonates after the 5th day of life. In 77% of all
      risk neonates with PVL, the diagnosis was made on the first day of life. After
      the first day of life, PVL was presented mainly in highly immature neonates. A
      correlation of PVL to gestational age could only be found in neonates with
      postnatal PVL. Subarachnoid space enlargement was found to be significantly more
      frequent in risk neonates with prenatal PVL than in risk infants with postnatal
      PVL. Residual ultrasound findings of PVL were significantly more frequent in male
      than in female risk neonates.

PMID- 9139502
TI  - [Adenomatoid tumor of the uterus--2 case reports].
AB  - We report two cases of the so-called adenomatoid tumor of the uterus, which have
      been detected in patients who underwent surgery for leiomyomas. The clinical
      signs, origin and immunohistochemical characteristics of the adenomatoid tumor
      are described. Adenomatoid tumors are slow growing epithelioid neoplasias with a
      co-expression of vimentin and cytokeratins. The characteristic cytokeratins are
      numbered 7, 8, 18, 19 and 5. The mesothelial histogenesis of the tumor can be
      confirmed. Our results rule out origins from Mullerian or mesonephrogenous ducts
      and angioma or adenoma. Considering our experiences, adenomatoid and leiomyoma
      cannot be distinguished macroscopically. The hysterectomy or salpingo
      oophorectomy, primarily performed under other diagnoses, are the therapies of
      choice.

PMID- 9139503
TI  - [The early postoperative period in patients with tumors of the posterior cranial
      fossa].
AB  - The studies carried out during an early postoperative period in patients with
      posterior fossa tumors were made to analyse the role of the degree and the level
      of brain stem damages in formation of cerebral reactions. The three groups of
      cases were selected in accordance with the course of the postoperative period:
      1.1-with exitus letalis (irreversible damages); 1.2-rehabilitation in persistent
      focal damages; 2-restoration with functional safety of brain stem. Differences of
      the integral cerebral reactions (the state of consciousness, emotional-affective
      disorders, awakening state) as well as the brain stem syndromes (formation of
      pathological systems, reciprocal relations between intact and destroyed brain
      stem structures) and diencephalic-subcortical syndromes were considered.

PMID- 9139504
TI  - [Borderline mental disorders in diabetes mellitus].
AB  - 124 patients with diabetes mellitus were examined in hospital of endocrine
      profile. The borderline mental disorders were revealed in 115 cases (92,7%) in
      the form of neurosis-like disturbances and pathological development of
      personality. Asthenic, asthenohypochondriac, asthenodepressive, obsessive and
      hysteroformic syndromes were diagnosed in patients with neurosis-like disorders.
      The personal disorders included asthenic, hysteric, obsessive, explosive and
      psychosomatic variations of development of the personality. Besides, poor
      cooperation of patients with the doctor was observed in the course of "diabetic
      control".

PMID- 9139505
TI  - [The clinical picture and therapeutic principles in mental disorders in women
      with a postoperative climacteric].
AB  - 49 patients after ovariectomy (OE) and 26 women after hysterectomy (HE) were
      examined. Psychiatrist's care was necessary for all of them because of marked
      mental disorders. The development of asthenic and dysthymic disorders was most
      typical after OE. OE induced the increase of depressive symptoms which acquired
      the neurotic and reactive signs when additional factors joined. Mental disorders
      after HE occurred as psychopathological symptoms of pseudopremenstrual syndrome
      and depressive and asthenic alterations in the pattern of menopausal syndrome.
      The development of hypochondriac personality was found in 22.5% of cases after OE
      and in 46.1% of patients after HE. Principles of therapeutic policy (correction
      of vegetovascular disturbances by combined application of substitution hormonal
      therapy, psychotropic drugs and psychotherapy) are formulated.

PMID- 9139506
TI  - [Positive psychotherapy in work with hospice patients].
AB  - A special psychosocial programme is described conducted in Arkhangelsk hospice.
      The programme is based on the approaches and methods of positive psychotherapy,
      intended for the patients, their relatives and medical staff of the hospice. Two
      years of the program implementation showed its high effectiveness for all the
      groups observed.

PMID- 9139507
TI  - [Changes in the cerebral circulation in persons with acquired heart defects].
AB  - A comprehensive estimation of the state of cerebral circulation was performed in
      57 patients with acquired heart valve diseases (AHVD) of different types,
      etiology and severity. Doppler sonography, rheoencephalography and quantitative
      electroencephalography were used. It was determined that the alterations of
      cerebral circulation in patients with AHVD were first of all caused by
      disturbances of venous outflow due to congestive heart failure. Other factors,
      which had also influence on the results of the studies performed are outlined.

PMID- 9139508
TI  - [A clinical electroneurophysiological study of neuromuscular system function in
      patients with diabetes mellitus types 1 and 2].

PMID- 9139509
TI  - [The structure of the diagnosis of neuromuscular diseases (the examination chart
      of outpatients for computer analysis)].
AB  - To provide a prophylactic medical examination (PME) as well as to improve the
      quality of diagnosis and treatment in a local medical institutions special coded
      card case sheets for patients with neuro-muscular disease adapted for computer
      analyzes are proposed. Such sheets facilitated determination of the diagnosis,
      objective patient's state during PME and correction of the scheme of therapy. The
      sheets were elaborated for long-term observation of 3153 patients with different
      neuro-muscular diseases and syndromes. The scheme of the diagnosis included such
      indices as character of damage of motor unit, type of heritability, age of onset
      of the disease, main systems of muscular atrophies, rate of the progress of
      pathological process, severity of the patient's state.

PMID- 9139510
TI  - [The clinical and psychological aspects of the reaction to disease (the problem
      of nosogenias)].
AB  - "Nosogenias" is the term describing some reactive states. They account for 15-90%
      of all the patients of somatic hospital. They are due to constellation of some
      psychotraumatic events related to somatic disease. A total of 166 patients were
      examined, among them 55 patients with ischemic heart disease, 56 cases with
      hypertension and 56 ones with bronchial asthma. The results evidence for the
      existence of two independent vectors which characterise "extremal" points of
      continuum of disease perception. The importance of somatic trouble (hyper- or
      hyponosognomia) was the basis of the first vector while the degree of
      completeness of independent and the whole image of disease as something which
      differed from "self" (ego-dystonic and ego-syntonic perception of disease) was
      the basis of the second vector. Combination of the above vectors with clinical
      and psychological characteristics in the whole clinical pattern of disease was
      recorded.

PMID- 9139511
TI  - [The mechanisms of psychological defense].

PMID- 9139512
TI  - [The management of psoriatic skin involvement in larvated depression].

PMID- 9139513
TI  - [The use of correctors of the lipid peroxidation and hemostasis processes in the
      combined treatment of patients with cerebrovascular disorders].

PMID- 9139514
TI  - [The clinico-epidemiological characteristics of tick-borne encephalitis in the
      central Urals].

PMID- 9139515
TI  - [The problems of irresponsibility and decreased responsibility in the works of
      the outstanding jurist of Russia, A. P. Kunitsyn].

PMID- 9139516
TI  - [Changes in the nervous system during chronic exposure to ionizing radiation].

PMID- 9139517
TI  - Effects of verapamil in ventricular tachycardias. An experimental and clinical
      study.
AB  - To determine the effect of verapamil in ventricular tachycardias, we performed an
      experimental and clinical study. Experimental ventricular tachycardias (VT) were
      produced in dog hearts with minute aconitine crystals introduced into the
      periphery of a left ventricular area, damaged by intramural injection of 1.0-1.5
      ml phenol. The response of these tachycardias to 0.2 mg/kg verapamil was
      analyzed. Verapamil was infused into the superior vena cava over 15-20 min. Leads
      II, aVL, intraventricular right and left unipolar records, as well as one of the
      superior vena cava, were registered under control conditions, in the presence of
      VT, and after application of verapamil. Recordings were obtained at constant
      intervals, waiting for the recovery of sinus rhythm (SR) and the posterior
      reappearance of tachycardia. Experiments were performed for 6 to 8 h under
      continuous infusion of Hartmann's solution. Throughout these periods, variations
      in systemic systolic pressure were recorded. From 75 animals submitted to this
      treatment, 30 (40%) recovered transiently the SR, whereas the drug exerted no
      antiarrhythmic effect in 19 (25%), and arterial systolic pressure fell
      importantly in 10 (13%) animals. In two more groups, of 15 dogs each, the VT
      response to verapamil was compared with the response to lidocaine and flecainide.
      Endovenous verapamil (5-10 mg) was administered to 10 patients, coursing with VT
      and having a structurally normal heart, after this arrhythmia was induced by
      electrical stimulation. The response to verapamil was satisfactory in nine
      patients (90%), in which VT originated in the septal and apical regions of the
      left ventricle. Verapamil seems to be effective in experimental and clinical
      ventricular tachycardias related to calcium-dependent potentials, in which the
      sustaining mechanism could either be triggered activity or reentry.

PMID- 9139518
TI  - Postinfarction cardiac rupture and electromechanical dissociation.

PMID- 9139519
TI  - Cardiac arrhythmias in patients on maintenance hemodialysis.
AB  - Cardiac arrhythmias were evaluated in 20 patients (14 males and 6 females; 38.2
      +/- 17.6 years) undergoing regular maintenance hemodialysis (HD) for chronic and
      renal failure (CRF) by Holter ECG monitoring a 24-hour period. Ventricular
      arrhythmias (VAs) were observed in 18 of 20 patients (90%). Sporadic VAs were
      recorded in 75% and frequent VAs in 15% of 20 patients. It was found that VAs
      were correlated with an increase in duration of CRF, but there was no relation
      with age, duration of HD, frequency of HD, body surface area, the levels of serum
      sodium, chloride creatinine, phosphorous (P), magnesium, free calcium (Ca), and
      free fatty acids, Ca x P, cardiothoracic ratio, ejection fraction, fractional
      shortening, interventricular septum thickness, left ventricular wall thickness,
      left ventricular end-diastolic dimension and left ventricular end-diastolic
      index. VAs recorded frequently during HD and for 4 hours after HD. In addition,
      sporadic supraventricular arrhythmias (SVAs) were observed in 16 patients (80%)
      and frequent SVAs were recorded in 2 patients (10%). It was concluded that
      cardiac arrhythmias frequently developed in patients with CRF receiving HD, VAs
      significantly increase during HD and for 4 h after HD and frequency of VAs may be
      correlated with duration of CRF and the use of acetate as a buffer in the
      dialysate.

PMID- 9139520
TI  - ANP concentrations during interchanging DDD-VVI pacing modes in patients with
      retrograde ventriculoatrial conduction.
AB  - The main reason for the pacemaker syndrome during VVI pacing is the existence of
      ventriculoatrial conduction (V-AC). Twenty-five patients with a permanent DDD
      pacemaker and ventriculoatrial conduction were included in the study. IN those
      patients the hemodynamic changes were evaluated in relation to ANP plasma
      concentration changes during different modes of pacing. After a resting period of
      30 minutes in the supine position ANP plasma concentration and blood pressure
      were evaluated: a) under DDD atrioventricular pacing at 90/min and for 30 minutes
      and b) under VVI pacing at 90/min and for 30 minutes. A decrease of systolic
      blood pressure by 12.77% (P < 0.0001) and diastolic blood pressure by 10.50% (P <
      0.0001) was noticed during VVI pacing. ANP was increased during VVI pacing by
      215.95% (P < 0.0001). It was observed that the acute transition from DDD to VVI
      pacing leads to a 3-fold increase in the levels of plasma ANP; this may be
      partially responsible for the pathogenesis of the haemodynamic changes during VVI
      pacing mediated through the direct hypotensive effect in addition to the
      coincidence of atrial and ventricular contraction. This study also proves the
      role of the increased systolic stress of atrial myocardium for the increased ANP
      secretion.

PMID- 9139521
TI  - Determinants of physical performance at cycloergometer in healthy middle aged men
      in Italy. The ECCIS project. Epidemiology and Clinics of Silent Ischemic Heart
      Disease.
AB  - OBJECTIVE: The purpose of this analysis is to relate the performance at
      cycloergometer of healthy middle aged men, identified in a population, with a
      number of personal characteristics to explain part of their physical fitness
      indicators. SETTING AND PARTICIPANTS: A sample of 5,163 men aged 40-59, belonging
      to sedentary occupational groups in Florence and Rome, were screened by a complex
      diagnostic procedure (participation rate = 66.3%). 3,893 were judged "healthy"
      from the cardiovascular point of view. MEASURES: A cycloergometric test and the
      measurement of some individual characteristics allowed to correlate indicators of
      performance at exercise (work load, test duration, work load/heart rate, PWC150
      and PWC150/kg) with body mass index, resting pulse rate, systolic, diastolic and
      mean blood pressure. HDL and non-HDL cholesterol, a score of physical exercise
      and cigarette consumption. RESULTS: Univariate and multivariate analysis showed
      significant relationship of exercise performance indicators with age, resting
      pulse rate, blood pressure, cigarette consumption (inverse) and with physical
      exercise score (direct). These individual characteristics could explain 14-15% of
      the variance of exercise performance indicators. CONCLUSIONS: The analysis could
      not establish how much the individual characteristics were causes or effects of
      individual physical fitness. A reasonable cause effect relationship can be argued
      for physical exercise score and likely for cigarette smoking. Relatively large
      differences in performance indicators can be expected for people with largely
      different individual characteristics.

PMID- 9139522
TI  - Usefulness of isoproterenol in the induction of clinical sustained ventricular
      tachycardia during electrophysiological study.
AB  - Electrophysiological testing remains the basic procedure in the assessment of
      life-threatening sustained ventricular tachycardias (VT). The predictive value of
      inducible VT depends on the baseline stimulation protocol and probably on some
      other factors, including automatic balance. We report the cases of four patients,
      with a history of myocardial infarction, who experienced recurrent episodes of
      syncope; the clinical aspects of the syncope were suggestive of syncopal VT. With
      a baseline protocol, electrophysiological testing only allowed the induction of
      well-tolerated non-sustained VT. Using the same stimulation protocol (rapid
      ventricular pacing or basal ventricular stimulation with 2 extra-stimuli),
      monomorphic sustained VT that had the same ECG morphology, as non-sustained VT,
      could only be induced while low doses of isoproterenol (1-2 micrograms/min) were
      being administered. In these cases, increased sympathetic tone appears to be
      prerequisite for a sustained VT reproducing the patients clinical symptoms and
      discomfort. To conclude, in some patients with recurrent symptoms, including
      syncope suggestive of ventricular arrhythmia, low-dose infusion of isoproterenol
      may facilitate the induction of of clinical sustained VT and increase the
      predictive value of electrophysiological testing. Possible mechanisms of
      ventricular arrhythmogenesis by isoproterenol are discussed.

PMID- 9139523
TI  - Joint meeting of the Belgian and Dutch Working Groups in Cardiology. Brussels,
      Belgium, 6-7 December 1996. Abstracts.

PMID- 9139524
TI  - Opioids in pain management. Proceedings of the 1st International Pain Center
      Symposium. Copenhagen, May 4-5, 1996.

PMID- 9139525
TI  - [General views in history of anatomy].

PMID- 9139526
TI  - [Research in urology. Rationale for research in urology].

PMID- 9139527
TI  - [Morbidity of and tolerance to ultrasonography-guided transrectal biopsy of the
      prostate].
AB  - OBJECTIVE: The objective of the study is to evaluate the infectious complications
      of the ultrasound-guided prostate transrectal biopsy using two different
      antibiotic prophylactic regimes. Also, patient tolerance to ultrasound-guided
      transrectal biopsy is assessed. METHODS: Prospective study in 100 patients
      randomized to antibiotic prophylaxis with Pefloxacin (800 mg as single dose)
      versus Ciprofloxacin (250 mg/8 h/72 h). Tolerance data collection was done
      through completion of a questionnaire immediately after biopsy. RESULTS: Out of
      the 92 patients eligible for the study, 44 (48%) were assigned to Pefloxacin and
      28 (52%) to Ciprofloxacin. In-house validation indicated both groups were
      matched. 90% patients showed good tolerance to the ultrasound technique and 81.5%
      patients to the transrectal biopsy. 31.5% patients presented no post-biopsy
      events; among the remaining only one patient (1%) required medical care and
      hospitalization. No patient had infectious complications. CONCLUSIONS: Prostate
      transrectal ultrasound and transrectal prostate biopsy was an approach well
      tolerated by most (81.5%) patients studied. Percentage of major complications was
      very small (1%), while post-biopsy events (haematuria, rectorrhage, etc) which do
      not require medical care should be considered not as complications but as effects
      intrinsic to the approach itself. Antibiotic prophylaxis whether with Pefloxacin
      or Ciprofloxacine was highly effective, although Pefloxacin is preferred due to
      its single dose administration and lower cost.

PMID- 9139528
TI  - [Factors influencing variability of PSA blood concentration in patients with
      prostate benign hyperplasia].
AB  - Study conducted in 107 patients with prostate benign hyperplasia to establish the
      influence that prostate volume, age, sexual activity, extent of obstruction and
      presence of urethral catheter have on PSA serum levels, using a linear regression
      model. In simple linear regression studies, a good correlation was seen between
      PSA serum concentration and prostate volume calculated by transrectal ultrasound
      (r = 0.57), which decreases when age in used as an independent variable (r =
      0.40). In multiple linear regression studies where all the variables are
      included, correlation increases slightly (r = 0.60), and only prostate volume and
      sexual activity are significant. Prostate volume in the single most influential
      factor on PSA levels in prostate benign hypertrophy although it is not the only
      parameter to be taken into account in serum level variations of this marker. Age
      influence can be secondary to other factors such as sexual activity.

PMID- 9139529
TI  - [Variability of rectal examination of the prostate among various groups of
      observers].
AB  - Rectal examination (RE) of the prostate gland is compulsory to rule out the
      presence of prostate cancer (PC). Empirically, it is defined as an examination
      burdened with a high degree of subjectivity and difficult to reproduce. The
      objective of this retrospective study is to evaluate RE concordance between
      different groups of researchers. In 133 patients referred to our Centre with
      suspected PC, RE was performed by three groups of experimented urologists (2 in
      hospital and 1 out-hospital). Concordance between the different groups was
      evaluated using Kappa's index (K). Kappa's index between out- and in-hospital
      urologists was 70%, 71% and 78%. Concordance of RE findings between the different
      groups of urologists can be considered good, since no significant differences
      were found relative to ER positive predictive value.

PMID- 9139530
TI  - [Biochemical study of testicular biopsy in infertility].
AB  - Basic semen tests nowadays contain no variables that may allow to certify that a
      man is fertile. Starting from this premise it could be clinically very useful,
      for the diagnosis of male infertility, to evaluate a parameter that may be
      related to sexual maturity and be specific of the germinal tissue, such as the C4
      lactate dehydrogenase isoenzyme (C4-LDH), which could indicate the activity of
      the germinal epithelium and the quality of the spermatozoa. In our experience, C4
      LDH activity in seminal plasma discriminates between fertile and non-fertile
      males; also, their testicular study has a good correlation both with
      histologically diagnosed disease and the seminal plasma levels. All of which
      suggest the diagnostic validity of plasma C4-LDH in male infertility, as a
      routine test which thus precludes the use of invasive techniques in the patient.

PMID- 9139531
TI  - [Topical anesthesia with the EMLA cream: application in pediatric urology].
AB  - EMLA Topical cream is a mixture of two local anaesthetics of the aminoamides
      group (lidocaine and prilocaine) with the ability to penetrate healthy skin.
      Since 1979 it has been used with good results in those countries where it is
      available, and where it has become a routinely used compound. In urology, it has
      been used to release is balanopreputial adherences as a skin anaesthetics in ESWL
      sessions, cauterization of penial injuries, etc. With the aim evaluating the
      efficacy of this cream in paediatric urology a prospective study was conducted in
      15 boys undergoing release of balanopreputial adherences and 5 girls undergoing
      venous catheterizations. Following topical application of the cream and a 90 min
      median occlusion time, an 80% efficacy level was observed in both groups.
      Considering these results, which are similar to those seen in the literature, we
      believe that this compound is useful for ordinary practice.

PMID- 9139532
TI  - [Multicystic renal dysplasia. Our experience with surgical treatment with early
      hospital discharge].
AB  - MRD is the most common form of renal cystic disease. It comprises severe
      dysplasia of the kidney, which adopts a non-reniform configuration, with the
      absence of a calyceal drainage system. Diagnosis is by ultrasound. Management of
      this non-functional mass has been traditionally surgical, although most recently
      a conservative approach with follow-up by periodical monitoring has been
      postulated by several schools.

PMID- 9139533
TI  - [Diagnosis of leukemic infiltration of the prostate p6ompted by PSA elevation].
AB  - Presentation of one case-report of leukaemic infiltration of the prostate.
      Interestingly, the biopsy was only performed after finding distinctly elevated
      PSA levels and not because of the clinical findings, whether exploratory or
      echographic.

PMID- 9139534
TI  - [Conservative treatment in major kidney trauma].
AB  - The kidney is frequently involved in penetrating abdominal injuries, and less so
      in closed abdominal traumatism. This paper presents one case of major renal
      trauma with total renal fracture and development of urinoma that separated both
      segments that, after a minimally invasive manoeuvre (percutaneous drainage),
      evolved favourably thus avoiding a surgical procedure which, quite reasonably,
      would have led to nephrectomy.

PMID- 9139535
TI  - [Retrotrigonal bladder lymphoma].
AB  - Presentation of one case of vesical involvement due to lymphoma in an 82-year old
      female which presented as a micturition syndrome, abdominal mass and later
      picture of obstructive uropathy with acute renal function impairment. Diagnosis
      was achieved by ultrasound and abdominal CAT, cystoscopy with of vesical biopsy,
      transvaginal mass biopsy and immunohistochemical techniques. The difficulties of
      a correct differential diagnosis with other vesical neoplasias as well as the
      need to differentiate primary from systemic vesical lymphoma were discussed, not
      only because of the separate prognosis but also for the different therapeutical
      approaches.

PMID- 9139536
TI  - [Cranial blind ureter: a new case].
AB  - One of the anomalies affecting the ureter is the blind bifid cranial ureter,
      which is truly an uncommon alteration. Clinical signs and symptoms are very
      ambiguous, and sometimes the condition is diagnosed accidentally while conducting
      an urographic examination. The aim of this paper is simply to contribute a new
      case to the existing literature.

PMID- 9139537
TI  - [Disk kidney. Report of a case].
AB  - Crossed fused renal ectopia (CFRE) is a rare anomaly, the incidence of which is
      estimated in one case per 700-1,000 births. We present here one case of Disk
      Kidney, an uncommon variant of CFRE, diagnosed in a female adult patient. Fused
      renal congenital anomalies are reviewed and the etiologies and presentation forms
      commented.

PMID- 9139538
TI  - [Relationship between a benign fibroepithelial polyp and a pelvic nephroblastoma:
      report of a case].
AB  - The purpose of this paper is to report one case of left pyelic Wilms' tumour in a
      17-year old male patient. Pre-operative diagnosis was complicated by a background
      of prior surgery on the same kidney due to a benign fibroepithelial polyp. The
      possible concomitences are analyzed while the relevance of an extensive
      pathoanatomical study to avoid possible diagnostic errors is emphasized.

PMID- 9139539
TI  - [Intravesical migration of an artificial urinary sphincter AMS-800: a rare
      complication].
AB  - Presentation of two cases of a patients with urinary incontinence of neurogenic
      origin treated by means of an artificial urinary sphincter graft AMS-800 who
      suffered the complication of intravesical migration of the occlusive cuff in one
      case, and pressure balloon and occlusive cuff in the second one. In the latter,
      the pressure balloon underwent a process of intravesical calcification. A review
      of the literature on the etiopathogeny of this complication and management of
      these patients is conducted.

PMID- 9139540
TI  - [Laparoscopic-extraperitoneal colposuspension].
AB  - Female stress urinary incontinence is a highly prevalent disease with a broad
      range of surgical approaches with different percentages of success depending on
      the severity of the condition and the appropriateness of the technique in the
      indication. A few years ago, laparoscopy was introduced as another therapeutical
      possibility. The paper presents the Burch-like colposuspension through an
      extraperitoneal laparoscopic approach for the first time in our country,
      describing the technique and the preliminary results with a mean follow-up of
      over 6 months. Our preliminary results, as well as the more numerous from other
      authors seem to indicate that when a Burch-like colposuspension is indicated,
      extraperitoneal laparoscopic approach may be the ideal one once the learning
      curve for laparoscopic surgery is overcome.

PMID- 9139541
TI  - [BCG immunotherapy and vulgar warts].

PMID- 9139542
TI  - The narrative and rhetoric of dreams: six literary fragments by a novelist.
AB  - Four of a novelist's dreams and two contemporaneous pieces of her fiction are
      examined through the lens of poststructuralism; thus viewed they display
      narrative coherence in form and content, a reciprocal interaction between dream
      and written day residue, and a rhetorical function in trauma resolution. Lacan's
      theories about the linguistic nature of the unconscious are particularly powerful
      in understanding these six works especially their recourse to figurative language
      in deconstructing and reconstructing the traumatized self. Dream narratology
      suggests the close relation of unconscious processes to creativity and the unity
      of storymaking and personal meaning. Narrative conventions in these dreams and
      related fiction illustrate the functions of metaphor and metonymy in traversing
      Lacan's "registers of experience" and his ideas about the "itinerary of the
      signifier," the way dreams and art capture the elusive object of desire.
      Creativity serves not only a wish-fulfillment function but also a self
      fulfillment function. Dreams, then, as creative acts, claim a privilege unto
      themselves and support Lacan's argument for a therapeutic approach of
      "desirelessness."

PMID- 9139543
TI  - On the "true-false" memory syndrome: the problem of clinical evidence.
AB  - A patient in twice-a-week psychoanalytic psychotherapy began to recover childhood
      memories of chronic sexual abuse, including oral, anal and genital penetration.
      These memories sometimes included bizarre content that created skepticism
      regarding their authenticity. However, this dubious quality was in marked
      contrast to the internal consistency, continuity, and emotional authenticity of
      the psychotherapeutic process. Criteria for attempting to distinguish between
      fantasy and reality are noted. Despite their tenuous nature, these criteria are
      important because, most frequently, they will be the only data available within
      the clinical situation.

PMID- 9139544
TI  - Cultural psychopathology and the false memory syndrome debates: a view from
      psychoanalysis.

PMID- 9139545
TI  - Dynamically oriented psychotherapy with borderline patients.
AB  - This article outlines a basic framework and strategy for a dynamically oriented
      psychotherapy with borderline patients. Focus includes arrangements and
      guidelines for psychotherapy, neutrality, the stability of the therapeutic
      environment, the therapeutic alliance, transference, the countertransference,
      activity of the therapist, types of interventions, style of interventions,
      interventions regarding core difficulties, the conceptual framework of anxiety
      and defense, trends in the psychotherapy, and termination. A differentiation
      between analytically oriented psychotherapy and dynamically oriented
      psychotherapy is provided. For one group of borderline patients, a modified
      analytically oriented approach is utilized throughout the entire treatment. For a
      second group, there is a switch from analytically oriented psychotherapy to a
      dynamically oriented psychotherapy, after the therapeutic alliance has become
      reasonably stable. Two clinical vignettes are provided.

PMID- 9139546
TI  - Psychotherapy with HIV-positive gay men: a psychodynamic perspective.
AB  - This paper examines psychotherapy with HIV-positive gay men from a psychodynamic
      perspective. Adjustment to being HIV-positive is conceptualized as an ongoing
      process of confrontation with loss and uncertainty. Interventions offered to HIV
      positive gay men range from counseling, indicated in response to an
      "uncomplicated" adjustment process; to dynamically oriented psychotherapy,
      indicated when the functioning of the self has been thrown off balance by HIV
      illness. The client's process of accepting his HIV illness is shaped and colored
      by the degree to, and manner in, which he has accepted being gay and integrated
      this into his identity. Sexuality is a core theme in psychotherapy with this
      population. It often plays a prominent role in the past unresolved conflicts
      (feelings about having become HIV-infected) as well as present concerns (feelings
      about living with HIV illness) which the client has come to therapy to address.
      The process of addressing the meanings being HIV-positive holds for the client in
      therapy can promote acceptance of the illness and cohesiveness of the self.
      Cultural and subcultural differences in how life stress is experienced must also
      be taken into account by the therapist in order to fully appreciate the client's
      concerns.

PMID- 9139547
TI  - Abraham Lincoln, psychotherapist to the nation: the use of metaphors.
AB  - Metaphors are widely utilized in psychotherapy to effect change in patients.
      Psychotherapeutic metaphors, in their various versions, may offer new choices and
      ways of viewing oneself to the patient which are more palatable than straight
      discussions or sterile insights. By addressing resistances indirectly, metaphors
      can be an effective tool for the therapist to use, regardless of theoretical
      orientation. Abraham Lincoln, a master of metaphor, utilized this tool
      effectively in dealing with crises and the ultimate fragmentation, disunion of
      the national identity. The author argues that Lincoln was able to address complex
      issues (such as slavery, liberty, nationhood, union, and conduct of the war) with
      metaphors, much as a skilled psychotherapist addresses complex issues within his
      or her purview. Abraham Lincoln effectively disarmed his critics, established a
      means of communication with the people, and sought to make his points in an
      understandable nonconfrontational fashion. These are skills highly valued by
      psychotherapists. One might say that Abraham Lincoln conducted psychotherapy on a
      national scale. Without formal training, he was ultimately able to create a new
      and more stable sense of national self using a metaphorical approach.

PMID- 9139548
TI  - Toward a multimodal communication theory of psychotherapy: the vicarious
      coprocessing of experience.
AB  - "Talking" therapy is examined as an interpersonal transaction. The personal
      experience narrative is used as a vehicle through which the patient and therapist
      coprocess a mutual experience. Within the narrative transaction, the patient is
      able to vicariously re-experience and reconfigure the narrated events as he/she
      believes the therapist is experiencing them. Nonverbal symbolic modes of
      communication such as music, movement, and art also provide media through which
      patients and therapists can coprocess a mutual experience. The vicarious
      coprocessing of experience is a therapeutic factor common to talking therapy,
      music therapy, art therapy, movement therapy, conventional social interaction,
      and some healing practices in other cultures.

PMID- 9139549
TI  - Power in the hypnotic relationship: therapeutic or abusive?
AB  - The unique relationship between hypnotist and subject has been theorized as one
      explanation for the effectiveness of hypnosis. This relationship carries a power
      differential, present in most therapeutic relationships, but accentuated by
      hypnosis. The power differential is sometimes perceived as the ability of the
      hypnotist to control the subject. Perceptions of hypnosis offered by stage
      hypnotists, the popular media, and some clinicians perpetuate the notion that the
      hypnotist has the ability to exert undue influence upon the client. The present
      article examines the relationship between hypnotist and subject focusing on
      issues of power and control. The authors examine the unique dynamics accompanying
      the use of hypnosis and their impact on the therapeutic dyad. Evidence is offered
      demonstrating the power differential, and how this differential can serve as
      either a positive or negative agent of change. Therapists should be aware of the
      dynamics created by using hypnosis. Implications for training therapists in the
      use of hypnosis are suggested.

PMID- 9139550
TI  - The actor-director and patient-therapist relationships: a process comparison.
AB  - The relationship between the actor and director, like that between the patient
      and psychotherapist, relies on intense emotional involvement. Both demand
      sensitivity, reciprocity, and a deep understanding of human behavior. Because
      dramatic action is created through continuous conflict between characters, actors
      must explore not only their actions, but also the reactions of those with whom
      they are in relationship. The process of therapy is equally interdependent.
      Through the relationship, therapists provide a context in which their patients
      can work through their conflicts. As in the rehearsal process, actions are
      explored in a supportive environment. This paper has presented a process
      comparison of the actor-director and patient-therapist relationships by proposing
      that both are art forms that rely on the skill of a trusted facilitator. Some of
      the techniques explored include: empathic attunement, emotional recall,
      transference, overcoming performance obstacles, improvisation, risk-taking, the
      pleasure principle, and creating a sense of family through new object relations.
      Like therapists, directors never forget that their work cannot be performed
      alone; it depends on interaction with the most delicate of phenomena: the human
      soul.

PMID- 9139551
TI  - Need and responsiveness in the treatment of a severely traumatized patient: a
      relational perspective.
AB  - Severely traumatized patients may exhibit poor functioning and a great deal of
      dependence upon the therapist. The question is raised as to what such patients
      truly need from a therapist, and the concept of optimal responsiveness is
      described. These patients may display complex blends of deficits, resulting from
      inadequate structuralization, together with pathological internal
      representations. Their expressed needs in therapy may be true requirements and/or
      expressions of wishes to be compensated for past suffering and refusal to assume
      adult functioning. Discerning what might constitute optimal responsiveness to
      true needs may be further complicated by the propensity some of these patients
      have for dysfunctional and impulsive behavior. A case is presented that
      illustrates some of the difficulties in determining how to respond to intense
      expressions of need, including needs for constant availability of the therapist
      and for physical contact. It is concluded that although this patient did not need
      everything from the therapist that she initially thought that she did, her needs
      were so great that an outpatient treatment situation often seemed insufficient.
      Despite an overall positive outcome for the patient, the treatment experience was
      very difficult for the therapist.

PMID- 9139552
TI  - Stimulation of megakaryocyte and platelet production by a single dose of
      recombinant human thrombopoietin in patients with cancer.
AB  - BACKGROUND: Thrombocytopenia is frequently encountered in patients with cancer.
      It is associated with an increased risk for clinically important bleeding
      episodes, which increases the demand for platelet transfusion. OBJECTIVE: To
      assess hematopoietic response to and clinical tolerance of recombinant human
      thrombopoietin, a recently cloned novel cytokine. DESIGN: Phase I and II clinical
      cohort study. SETTING: The University of Texas M.D. Anderson Cancer Center,
      Houston, Texas. PATIENTS: 12 patients with sarcoma who had high risk for severe
      chemotherapy-induced thrombocytopenia. INTERVENTION: A single intravenous dose of
      thrombopoietin (0.3 to 2.4 micrograms/kg of body weight) 3 weeks before
      chemotherapy. MEASUREMENTS: Peripheral blood and bone marrow evaluation before
      and after thrombopoietin administration. RESULTS: A single dose of thrombopoietin
      was associated with an increase in platelet counts (mean increase from baseline,
      61% to 213%; P = 0.002) in a dose-related manner. This increase began by day 4 in
      most patients and peaked on a median of day 12. This sustained response was
      associated with a prolonged serum thrombopoietin half life (20 to 30 hours). The
      platelets appeared morphologically normal and showed normal aggregation in
      response to various agonists. Platelet response was accompanied by a dose-related
      increase in bone marrow megakaryocytes (as much as 4-fold); the expansion of the
      bone marrow progenitors of myeloid, erythroid, multipotential, and megakaryocytic
      lineages; and the marked mobilization of progenitors (maximum, 5.7-fold to 10
      fold) of multiple cell lineages in the peripheral blood. Treatment was well
      tolerated, and no serious adverse events occurred. CONCLUSIONS: Thrombopoietin,
      administered as a single dose, is a potent stimulus for prolonged platelet
      production in humans. It merits further evaluation for the prevention and
      treatment of thrombocytopenia.

PMID- 9139553
TI  - Sustained biochemical and histologic remission of primary biliary cirrhosis in
      response to medical treatment.
AB  - BACKGROUND: Treatment of primary biliary cirrhosis with ursodiol or colchicine
      may stabilize the disease or slow its rate of progression, but no reports of
      spontaneous or treatment-related remission have been published. OBJECTIVE: To
      determine whether primary biliary cirrhosis fully responds to low-dose oral
      methotrexate therapy. DESIGN: Prospective case study with at least 6 years of
      observation. SETTING: Academic medical center. PATIENTS: 5 of 19 patients with
      biopsy-proven precirrhotic primary biliary cirrhosis who had been ill for at
      least 1 year. Three of the 5 had not responded to colchicine or had responded
      only partially. INTERVENTION: Oral methotrexate, 15 mg/wk in divided doses.
      MEASUREMENTS: Symptoms, biochemical tests of liver function, and percutaneous
      liver biopsies. The latter were done at baseline, 1 to 2 years after initiation
      of methotrexate therapy, and then every 2 to 3 years during methotrexate therapy.
      RESULTS: All 5 patients completely responded to medical treatment. Results of
      biochemical tests of liver function, became normal, symptoms remitted, and serial
      liver biopsy specimens showed progressive histologic improvement. Biopsy
      specimens obtained after 5 to 12 years of treatment showed few signs of primary
      biliary cirrhosis and, in 3 patients, were close to normal. Five of the other 14
      patients have responded biochemically and have shown histologic improvement; the
      other 9 have not responded to methotrexate therapy, have discontinued therapy, or
      have been lost to follow-up. CONCLUSION: In some patients, primary biliary
      cirrhosis may remit in response to methotrexate alone or in combination with
      colchicine or ursodiol.

PMID- 9139554
TI  - Weekly fluconazole for the prevention of mucosal candidiasis in women with HIV
      infection. A randomized, double-blind, placebo-controlled trial. Terry Beirn
      Community Programs for Clinical Research on AIDS.
AB  - BACKGROUND: Candidiasis is a frequent complication of infection with the human
      immunodeficiency virus (HIV); however, few data exist about the natural history,
      prevention, and treatment of mucosal candidiasis in women. OBJECTIVE: To evaluate
      the safety and effectiveness of weekly fluconazole prophylaxis for mucosal
      candidiasis in women infected with HIV. DESIGN: Randomized, double-blind, placebo
      controlled trial. SETTING: 14 sites participating in the Community Programs for
      Clinical Research on AIDS (CPCRA). PATIENTS: 323 women with HIV infection and
      CD4+ cell counts of 300 cells/mm3 or less. INTERVENTION: 200 mg of fluconazole
      per week or placebo. Open-label fluconazole for candidiasis prophylaxis was
      permitted after two oropharyngeal or vaginal episodes or one esophageal episode.
      MEASUREMENTS: Development of mucosal candidiasis, clinical and in vitro
      resistance of Candida species to fluconazole, survival, and adverse events.
      RESULTS: After a median follow-up of 29 months, 72 of 162 patients receiving
      fluconazole and 93 of 161 patients receiving placebo had at least one episode of
      candidiasis (relative risk [RR], 0.56 [95% Cl, 0.41 to 0.77); P < 0.001). Weekly
      fluconazole was effective in preventing oropharyngeal candidiasis (RR, 0.50 [Cl,
      0.33 to 0.74]; P < 0.001) and vaginal candidiasis (RR, 0.64 [Cl, 0.40 to 1.00]; P
      = 0.05) but not esophageal candidiasis (RR, 0.91 [Cl, 0.48 to 1.72]; P > 0.2).
      Relative risks were similar for women who had a history of mucosal candidiasis
      (RR, 0.5 [Cl, 0.35 to 0.75]) and those who did not (RR, 0.69 [Cl, 0.35 to 1.34]).
      Absolute risk reduction for patients with a history of infection was 25.6 per 100
      person-years, which is more than twice the reduction of 11.2 per 100 person-years
      seen in patients with no history of infection. This difference reflects the
      higher risk of patients who previously had an infection. Candida albicans was not
      usually resistant to fluconazole in vaginal specimens in clinical or in vitro
      settings; such resistance occurred in less than 5% of patients in each group.
      CONCLUSIONS: Weekly fluconazole (200 mg) seems to be safe and effective in
      preventing oropharyngeal and vaginal candidiasis. This regimen has a useful role
      in the management of HIV-infected women who are at risk for recurrent mucosal
      candidiasis.

PMID- 9139555
TI  - Treatment of shigellosis: V. Comparison of azithromycin and ciprofloxacin. A
      double-blind, randomized, controlled trial.
AB  - BACKGROUND: Treatment of shigellosis is currently limited by the high prevalence
      of multidrug-resistant strains of Shigella. OBJECTIVE: To determine the efficacy
      of azithromycin in the treatment of shigellosis. DESIGN: Randomized, double-blind
      clinical trial. SETTING: Diarrhea treatment center in Dhaka, Bangladesh.
      PATIENTS: 70 men with shigellosis that had lasted 72 hours or less.
      INTERVENTIONS: Patients stayed in the hospital for 6 days. Thirty-four patients
      were randomly assigned to receive 500 mg of azithromycin on study day 1, followed
      by 250 mg once daily for 4 days; 36 patients were assigned to receive 500 mg of
      ciprofloxacin every 12 hours for 5 days. MEASUREMENTS: Clinical treatment failure
      was considered to have occurred if frank dysentery persisted for 72 hours after
      therapy began or if on study day 5 a patient had more than six stools, had any
      bloody-mucoid stools, had more than one watery stool, or had an oral body
      temperature exceeding 37.8 degrees C. Bacteriologic treatment failure was
      considered to have occurred if Shigella strains could be isolated from a stool
      sample after study day 2. Therapy was considered either clinically or
      bacteriologically successful in patients who completed therapy and did not meet
      criteria for failure. RESULTS: Therapy was clinically successful in 28 (82%)
      patients who received azithromycin and 32 (89%) patients who received
      ciprofloxacin (difference, -7% [95% Cl, -23% to 10%]). Therapy was
      bacteriologically successful in 32 (94%) patients receiving azithromycin and 36
      (100%) patients receiving ciprofloxacin (difference, -6% [Cl, -14% to 2%]). Peak
      serum concentrations of azithromycin were equal to the minimum inhibitory
      concentration (MIC) of the infecting Shigella strains, whereas serum
      concentrations of ciprofloxacin were 28 times the MIC. Stool concentrations of
      both drugs were more than 200 times the MIC. CONCLUSION: Azithromycin is
      effective in the treatment of moderate to severe shigellosis caused by multidrug
      resistant Shigella strains.

PMID- 9139556
TI  - Gastroesophageal reflux disease presenting with intractable nausea.
AB  - BACKGROUND: Typical symptoms of gastroesophageal reflux disease are heartburn and
      regurgitation. A subset of patients present with atypical symptoms, such as chest
      pain, cough, wheezing, and hoarseness. OBJECTIVE: To review the clinical
      presentation and treatment of patients who presented with nausea as the primary
      symptom of gastroesophageal reflux disease. DESIGN: Case series. SETTING:
      Outpatient department of a university hospital. PATIENTS: 10 outpatients who had
      chronic, intractable nausea and had not responded to empirical therapies.
      MEASUREMENTS: Patients were evaluated by esophagogastroduodenoscopy, 24-hour
      esophageal pH studies, gastric-emptying tests, electrogastrography, or a
      Bernstein test. RESULTS: Abnormal acid reflux was found to be the cause of
      intractable nausea in all 10 patients. In 5 of the 10 patients, esophagitis was
      documented by esophagogastroduodenoscopy. Six patients had abnormal results on
      the 24-hour esophageal pH study. In these 6 patients, 32 of 33 episodes of nausea
      were accompanied by an episode of acid reflux. One patient had positive results
      on the Bernstein test. Nausea resolved after treatment with omeprazole in 7
      patients, after treatment with cisapride or ranitidine in 2 patients, and after
      Nissen fundoplication in 1 patient. CONCLUSIONS: Intractable nausea is an
      atypical symptom that can occur in a subset of patients with gastroesophageal
      reflux disease. A 24-hour esophageal pH study should be considered in patients
      who have unexplained nausea but normal findings on esophagogastroduodenoscopy, a
      gastric-emptying test, and electrogastrography. Nausea related to
      gastroesophageal reflux disease resolves or is markedly reduced with proton-pump
      inhibitors or promotility drugs.

PMID- 9139557
TI  - Risk factors for deep venous thrombosis of the upper extremities.
AB  - BACKGROUND: Hypercoagulable states and triggering factors (surgery, trauma,
      immobilization, pregnancy, and use of oral contraceptives) are associated with an
      increased risk for deep venous thrombosis of the lower extremities. In contrast,
      risk factors for deep venous thrombosis of the upper extremities have not been
      identified. OBJECTIVE: To evaluate the prevalence of hypercoagulable states and
      triggering factors in patients with primary deep venous thrombosis of the upper
      extremities. DESIGN: Frequency-matched case-control study. SETTING: Hemophilia
      and thrombosis center at a university hospital. PATIENTS: 36 patients who had
      primary deep venous thrombosis of the upper extremities, 121 patients who had
      primary deep venous thrombosis of the lower extremities, and 108 healthy
      controls. Patients who had deep venous thrombosis of the lower extremities and
      study controls were frequency-matched by age, sex, geographic origin, and social
      status with patients who had deep venous thrombosis of the upper extremities.
      MEASUREMENTS: Resistance to activated protein C was evaluated by a clotting
      method based on the activated partial thromboplastin time. If test results were
      abnormal or borderline, DNA analysis for substitution in coagulation factor V
      gene was done. Antithrombin, protein C, protein S, antiphospholipid antibodies,
      and total plasma homocysteine levels were also measured. RESULTS: Prevalences of
      abnormalities of the natural anticoagulant system (9%) and hyperhomocysteinemia
      (6%) in patients who had deep venous thrombosis of the upper extremities were
      similar to prevalences of both factors in controls (6% and 7%, respectively) but
      lower than in patients who had deep venous thrombosis of the lower extremities
      (31% and 14%, respectively). Antiphospholipid antibodies were found only in
      patients who had venous thrombosis of the lower extremities (7%). The overall
      prevalence of hypercoagulable states in patients who had thrombosis of the upper
      extremities (15%) was similar to that in controls (12%) but was significantly
      lower than that in patients who had thrombosis of the lower extremities (56%). A
      recent history of strenuous exercise of muscles in the affected extremity was the
      most frequent triggering factor for patients who had deep venous thrombosis in
      the upper extremities (33%). CONCLUSIONS: This preliminary study indicates that
      the prevalence of hypercoagulable states is low in patients who have primary deep
      venous thrombosis of the upper extremities.

PMID- 9139558
TI  - Using numerical results from systematic reviews in clinical practice.
AB  - Systematic reviews summarize large amounts of information and are more likely
      than individual trials to describe the true clinical effect of an intervention.
      Traditional statistical outputs from systematic reviews cannot immediately be
      applied to clinical practice. The number needed to treat (NNT) has that clinical
      immediacy. This number can be calculated easily from raw data or from statistical
      outputs, and the principle involved in its calculation can be applied to
      different outcomes: treatment efficacy, adverse events (harm), or other end
      points. The NNT defines the treatment-specific effect of an intervention, and we
      suggest it as a currency for making decisions about individual patients. Knowing
      the NNT for different interventions that have the same outcome for the same
      disorder can help shape individual and institutional practice. Knowing or
      estimating the number needed to harm is also an important part of the equation.
      Knowing or estimating an individual patient's risk can, with the NNT, be a guide
      to the overall or net value of a prophylactic intervention. We advocate an
      approach to systematic reviews that distills information into, in effect, one
      number: the NNT. This is simple to remember and directly supports efforts to work
      with patients to make the best possible clinical decisions for their care.

PMID- 9139559
TI  - Intravenous immune globulin therapy for neurologic diseases.
AB  - High-dose intravenous immune globulin (IVIg) has emerged as an important therapy
      for various neurologic diseases. Different interpretations of clinical trial
      results; the expected benefit of IVIg compared with that of alternate therapies;
      and issues about IVIg's safety, cost, and mechanisms of action have raised
      concern and uncertainty among practitioners. To clarify these areas, this paper
      examines the clinical, serologic, and immunologic data on more than 110 patients
      with various autoimmune neurologic diseases who received IVIg during the past 6
      years at the National Institute of Neurological Disorders and Stroke. It also
      reviews work by other investigators on the efficacy, risks, benefits, and
      mechanisms of the action of IVIg in these diseases. In controlled clinical
      trials, IVIg has been effective in treating the Guillain-Barre syndrome,
      multifocal motor neuropathy, chronic inflammatory demyelinating polyneuropathy,
      and dermatomyositis. In other controlled or open-label trials and case reports,
      IVIg produced improvement in several patients with the Lambert-Eaton myasthenic
      syndrome and myasthenia gravis but had a variable, mild, or unsubstantiated
      benefit in some patients with inclusion-body myositis, paraproteinemic IgM
      demyelinating polyneuropathy, certain intractable childhood epilepsies,
      polymyositis, multiple sclerosis, optic neuritis, and the stiff-man syndrome. The
      primary adverse reaction was headache; aseptic meningitis, skin reactions,
      thromboembolic events, and renal tubular necrosis occurred rarely. The most
      relevant immunomodulatory actions of IVIg, operating alone or in combination, are
      inhibition of complement deposition, neutralization of cytokines, modulation of
      Fc-receptor-mediated phagocytosis, and down-regulation of autoantibody
      production. Therapy with IVIg is effective for certain autoimmune neurologic
      diseases, but its spectrum of efficacy has not been fully established. Additional
      controlled clinical trials are needed.

PMID- 9139560
TI  - Thrombopoietin: platelets on demand?

PMID- 9139561
TI  - Primary biliary cirrhosis: questions and promises.

PMID- 9139562
TI  - Zinc gluconate lozenges for treating the common cold.

PMID- 9139563
TI  - Zinc gluconate lozenges for treating the common cold.

PMID- 9139564
TI  - Zinc gluconate lozenges for treating the common cold.

PMID- 9139565
TI  - Polymerase chain reaction for diagnosis of HIV infection.

PMID- 9139566
TI  - Chest pain and the esophagus.

PMID- 9139567
TI  - Somatostatin receptor scintigraphy in the Zollinger-Ellison syndrome.

PMID- 9139568
TI  - Three-year follow-up on the effects of transdermal estrogen.

PMID- 9139569
TI  - Thrombocytosis associated with low-molecular-weight heparin.

PMID- 9139570
TI  - Clinical course of deep venous thrombosis.

PMID- 9139571
TI  - Clinical course of deep venous thrombosis.

PMID- 9139572
TI  - Patients' expectations and demand management.

PMID- 9139573
TI  - Desmopressin nasal spray for hemophilia A and type I von Willebrand disease.

PMID- 9139574
TI  - Anaphylaxis and cerebral hyadatidic disease.

PMID- 9139575
TI  - Tamoxifen-induced female androgenetic alopecia in a patient with breast cancer.

PMID- 9139576
TI  - How much are we willing to pay for information about quality?

PMID- 9139577
TI  - Museum visit leading to insulin pump malfunction.

PMID- 9139578
TI  - Rethinking somatization.

PMID- 9139579
TI  - Developing critical pathways for the operating room.
AB  - Case management and managed care systems are emerging in the 1990s as ways to
      deliver quality, cost effective patient cae. The essential tool of managed care
      systems is a critical pathway, which is developed through the collaboration of
      health care team members. The critical pathway is an abbreviated version of the
      patients hospital course according to his or her medical diagnosis or case type
      and it allows health care team members to continually evaluate the patients care.
      It has helped team members at Johns Hopkins Hospital, Baltimore, identify more
      effective and cost-efficient ways to deliver patient care.

PMID- 9139580
TI  - Neurobiological principles of learning and memory.
AB  - An increasing flow of evidences collected on elementary forms of learning
      processes in selected animal models evidentiates some mechanisms which can
      represent the basic cellular principles underlying plastic changes: 1. 5HT and
      second messengers of nucleotide type (like cAMP) have a pivotal role in the
      learning process. 2. In almost all short-term learning processes the
      modifications are subserved by a mechanism of protein phosphorylation. 3. In
      various animal models the modulation of K+ and Ca2+ channels is the molecular
      mechanism for learning. Experiments performed in sensory T neuron of the leech
      indicate that the modulation of Na+/K+ electrogenic pump is one of the
      fundamental mechanism for learning. 4. In long-term plastic changes, the most
      important finding is that newly synthesized proteins are formed. 5. In addition
      to what has been observed in the Aplysia model, where changes in synaptic
      efficacy represent the basic principles of memory storage, in the leech it has
      been demonstrated that a molecular machinery present in a single neuron can adapt
      the activity of the cell to environmental stimuli.

PMID- 9139581
TI  - Naloxone blocks long-term depression of excitatory transmission in rat CA1
      hippocampus in vitro.
AB  - In rat hippocampal slices, high intensity tetanic stimulation (two 1 s trains of
      100 Hz separated by 20 s, 3-5X intensity of the test stimulus) of the Schaffer
      collateral-commissural (SCC) fibers induced a long-term depression (LTD) of the
      negative field excitatory postsynaptic potentials (fEPSP) in stratum radiatum of
      the CA1 region. The initial slope of the fEPSP, evoked by a single test shock
      applied to the SCC fibers, was depressed for a period longer than 40 min
      following such high intensity tetanic stimulation to this fiber system. However,
      the same tetanic stimulation delivered at low (test) intensity induced long-term
      potentiation (LTP) of the fEPSPs. Thus, similar patterns of stimulation can
      induce either LTP or LTD, depending on whether low- or high-intensity tetanic
      stimuli are delivered. The LTD induced by high strength tetanic stimulation was
      clearly blocked by the opioid antagonist naloxone (1 microM); however, the N
      methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonopentanoate
      (AP5; 50 microM) had no effect on the LTD. Our data suggest that the strong
      stimulation used for LTD induction may have activated other afferent fiber
      systems and/or local interneurons in addition to SCC fibers, such as the
      enkephalin-containing terminals of the perforant path (PP) projecting to the
      stratum lacunosum moleculare or opioid peptide-containing interneurons. Thus, the
      resulting release of endogenous opioid peptides could play a role in the cellular
      mechanisms involved in some forms of long-term synaptic depression.

PMID- 9139582
TI  - Hippocampal electrical activity and behavior in the rabbit.
AB  - Different approaches to the study of the relationship between hippocampal
      electrical activity and behavior have shown that hippocampal EEG varies according
      to different behavioral aspects. In particular, a rhythmic slow activity (RSA,
      Theta rhythm) can be recorded during voluntary movements and to a lesser degree
      during immobility. In laboratory experiments, we tried to evaluate the influence
      on the hippocampal EEG of external stimuli evoking emotional or cognitive
      responses. Similar electrical responses were observed during animal hypnosis and
      in the presence of threatening stimuli, while some electrical parameters, such as
      frequency and rhythmicity, varied according to the nature of the stimulus. In
      order to have greater and clearer information, we adopted a neuro-ethological
      approach ch. which allowed us to classify behavior into several categories and to
      record the hippocampal EEG during natural behavior. The influence exerted on
      hippocampal electrical activity by novel stimuli and the electrical profiles
      recorded during exploratory behavior or alert or quiet immobility allowed us to
      classify the hippocampal EEG on the basis of frequency and rhythmicity. Moreover,
      the study of social behavior showed that the variations of the electrical
      parameters of the hippocampal activity depended on the characteristics of the
      stimulus and that typical electrical profiles could be observed in immobile or
      motor activities caused by specific stimuli. Socially dominant and subordinate
      rabbits could also be distinguished on the basis of hippocampal electrical
      parameters.

PMID- 9139583
TI  - One or many arousal systems? Reflections on some of Giuseppe Moruzzi's foresights
      and insights about the intrinsic regulation of brain activity.
AB  - Soon after the birth of the hypothesis of the ascending brainstem activating
      system, Giuseppe Moruzzi considered the possibility that a fractionated and
      differentiated arousing action of the reticular formation is required for
      effective behavior and cognition. Current knowledge about the chemically tagged
      brainstem systems which project diffusely to thalamus, neocortex and limbic
      structures has justified the assumption of the existence of multiple arousal
      systems. Combined changes in the activities of these systems are responsible for
      the sleep-wake cycle and the modulation of the reactivity of the brain to
      environmental inputs. There remains the physiological problem--one which has
      always been foremost in Moruzzi's thinking about the intrinsic regulation of
      brain activity--of how the separate actions of the different arousal systems are
      brought together into a functional whole. This problem still awaits experimental
      answers.

PMID- 9139584
TI  - The neuroethology of cognitive maps: contributions from research on the
      hippocampus and homing pigeon navigation.
AB  - The rich ethological tradition that characterizes the homing behavior of pigeons
      offers an excellent opportunity to examine the importance of the hippocampal
      formation for the regulation of spatial cognitive mechanisms. The present review
      summarizes both anatomical and behavioral data obtained in researches on the
      pigeon hippocampal formation that have been performed over the last 12 years.
      Pathway connection studies and investigations on the neurochemical organization
      of the avian hippocampal formation show that this structure shares many
      similarities with the mammalian hippocampus and provide the basis for structural
      as well as functional homology. The initial research on the role of the
      hippocampal formation in the homing behavior showed that this brain structure is
      likely to be involved in phenomena of spatial cognition. Therefore, the homing
      behavior of pigeons has been extensively used as an experimental model to
      investigate the role of the hippocampal formation in spatial cognition related to
      a naturally occurring behavior. These studies have revealed that the hippocampal
      formation plays a fundamental role in the learning of a navigational map based on
      atmospheric odors, but it doesn't seem to be involved in the operation of such a
      map. In contrast, both the learning and the operation of a navigational map based
      on the recognition of familiar landmarks require a functional hippocampal
      formation. Further investigations indicated that these functions of the
      hippocampal formation are mediated by its involvement in the use of the sun
      compass, and suggested that the hippocampal formation plays a fundamental role in
      a cognitive process in which the sun compass is specifically used to learn about
      the location of stimuli in space. The studies reviewed in the present paper have
      provided a considerable amount of experimental data both on the
      anatomical/neurochemical organization of the avian hippocampal formation and on
      the role played by this brain structure in spatial cognition. The future
      development of these researches will need to consider the contribution to
      hippocampal function of specific transmitter systems that are involved in
      hippocampal circuitry. In particular, the afferent cholinergic system and some of
      the peptidergic systems intrinsic to the hippocampal formation deserve particular
      attention in view of their possible involvement in the acquisition and/or
      operation of spatial cognitive abilities by homing pigeons.

PMID- 9139585
TI  - [The immunomorphology of the mucosa of the bronchi and gastroduodenal zone in
      children with combined disease of the bronchi and gastrointestinal tract].
AB  - Mucous membrane of the bronchi, antral zone of the stomach and duodenum were
      studied histologically, morphometrically, immunohistochemically and
      bacterioscopically in 47 children of 5 to 14 years of age with bronchial asthma
      (16 patients), obstructive bronchitis (12 patients), chronic pneumonia or chronic
      nonspecific bronchitis (19 patients). All these children had also
      gastroduodenitis. There was an increase of local production of IgE and enhanced
      degranulation of mast cells in bronchial mucosa and gastroduodenal zone in
      children with bronchial asthma and obstructive bronchitis. The proportion of
      CD4+/CD8+ decreased to 0.92 in bronchial asthma. Gastritis was associated much
      more frequently with Helicobacter pylori in children with chronic obstructive
      bronchitis and bronchial asthma.

PMID- 9139586
TI  - [The morphofunctional characteristics of the palatine and pharyngeal tonsils in
      children with chronic tonsillitis and adenoids].
AB  - 22 palatine and 10 pharyngeal tonsils of 20 children, 4 to 15 years of age, with
      chronic tonsillitis and adenoids were studied histologically and
      immunohistochemically. The material was obtained at tonsillectomy, adenotomy and
      adenotonsillectomy. The expression of LCA, CD20, CD45 RO, CD45 RA, CD68 and HLA
      DR-antigen was determined immunohistochemically. Functional heterogeneity of the
      whole lymphoid population in the tonsil tissue is structured by dividing lymphoid
      tissue into T- and B-regions. However, this subdivision is relative.
      Interpenetration of T- and B-cells into structurally determined functional zones
      reflects cooperative cell relations in the immune response the obligatory
      participant of which are non-lymphoid cells of the microenvironment: antigen
      representing macrophages of the follicle germinative centres and reticular
      epitheliocytes in the regions of lymphoepithelial symbiosis. HLA-DR-antigen
      expression of the reticulum epithelium cells and the presence of activated T
      lymphocytes in the lymphoepithelial symbiosis zones allow one to consider these
      zones as an immunoregulatory compartment of the tonsils.

PMID- 9139587
TI  - [The importance of the cytological study of the tracheobronchial aspirate in
      newborn infants with the respiratory distress syndrome who are on artificial
      pulmonary ventilation].
AB  - Cytological and pH-metrical investigations of the tracheobronchial aspirate were
      performed in 43 children with a respiratory distress syndrome (RDS) on artificial
      pulmonary ventilation. The content over 40% in the cytogram of polymorphonuclear
      leukocytes (PNL) indicated infectious genesis and below 10%--noninfectious
      genesis of RDS. The content of PNL in the range of 11-39% requires additional
      clinical data which would help to establish RDS cause.

PMID- 9139588
TI  - [The morphogenesis of tick-borne encephalitis in light of the new data on virus
      replication].
AB  - The analysis of the RNA virus spread of tick encephalitis in the course of
      infection has been performed. The virus RNA is detectable first, (as early as one
      day after the infection) in the lymph nodes. Later it is retained in the cells of
      T-dependent areas. Viral RNA is also the first to be detected in the vascular
      structures and ventricular system of the brain. The correlation between the time
      of the viral RNA replication and specific initial damage in the lymphoid tissue
      and central nervous system is established. The question is raised on the role of
      the lymphocyte recirculation in the spread of the virus in the body.

PMID- 9139590
TI  - [Cytokines and their role in intercellular interactions].
AB  - Cytokines include interferons, colony-stimulating factors, interleukins and
      growth factors. 6 groups of cytokines are distinguished depending on the
      direction of their function. They provide regulation of intercellular
      interaction, initiate nonspecific inflammatory response, control growth and
      differentiation of hematopoietic and residential cells, activate the cells of the
      inflammatory infiltrate, stimulate hematopoiesis. Regulation of the cytokine
      activity is brought about at the level of their secretion, expression of the
      cytokines receptors as well as by means of other cytokines and soluble cytokine
      binding factors and inhibitors. The use of cytokines and antibodies against them,
      receptor antagonists and soluble cytokine receptors is increasing for
      immunotherapy of various diseases.

PMID- 9139589
TI  - [The morphological characteristics of diphtheria in adults under current
      conditions].
AB  - Clinico-anatomical analysis of 112 lethal cases of diphtheria in adults showed a
      grave course of the disease in chronic alcoholics at the age of 40-49 years. The
      morphological changes were characterized by a complex of typical changes at the
      primary focus, intracanalicular and hematogenous dissemination with high
      bacteremia. The morphology of pneumonia caused by Corynebacterium diphtheria is
      described for the first time. At the early stages of the disease infectious-toxic
      degeneration of the myocardium was documented with predominating alteration of
      the atrioventricular node or contractile myocardium. The above morphological
      features may be due to peculiarities of patients and decreased subjects as well
      as possible changes in the pathogen characteristics.

PMID- 9139591
TI  - [Peptic ulcer and liver pathology (an analysis of 6456 autopsy observations
      during 1983-1992)].
AB  - The incidence of various forms of stomach ulcer, their combination with liver
      diseases and pathogenetic relationships of these two pathological types have been
      studied on the material of 6456 autopsy cases for 1983-1992. High incidence of
      nonspecific reactive hepatitis in both gastric and duodenal ulcer and that of
      liver cirrhosis and cirrhosis-carcinoma in the pyloro-duodenal ulcer is
      established. A role of gastrin as a promoter in the development of liver
      cirrhosis and carcinoma in pyloroduodenal ulcer is suggested. The role of
      nonspecific reactive hepatitis in chronization of the hepatic pathological
      process is not excluded.

PMID- 9139592
TI  - [An immunohistochemical study of the expression of the oncoprotein p53 in
      astrocytic gliomas of the cerebral hemispheres].
AB  - p53 oncoprotein was studied in 80 astrocytic gliomas of the hemispheres and
      nuclear expression of this oncoprotein was found in 90% of the tumors this
      indicating high specificity of the reaction. A tendency to growing oncoprotein
      expression was found at different stages of malignant transformation showing
      feasibility of clonal expansion of cells with gene p53 mutation. High variability
      of the oncoprotein p53 immunoreactivity is characteristic of glioblastomas this
      suggesting genotypic polymorphism of gliomas of high grade malignancy. The lowest
      expression of the p53 oncoprotein was in gliosarcomas suggesting mechanism other
      than mutation. A stable link between the p53 oncoprotein expression and the
      proliferating cells nuclei antigen was not observed. This finding confirms an
      independent character of various progression features of the tumor.

PMID- 9139593
TI  - [The intermitochondrial contacts of cardiomyocytes during cardiac adaptation
      under pathological conditions].
AB  - Intermitochondrial junctions (IMJ)-recently described intracellular structures
      were investigated in order to evaluate their role in pathology. Chronic and acute
      pathological processes including myocardial hypertrophy and its regression,
      chronic alcohol cardiomyopathy, acute pancreatitis and acute diffuse peritonitis
      were modelled in 106 male rats. The myocardial tissue was studied histologically,
      electron-microscopically and morphometrically. It is shown that myocardial
      hyperfunction morphology is due to the heart functional overload that requires
      its adequate energy supply. Therefore, apart from the mitochondrial hyperplasia,
      their association by means of IMJ occurs. IMJ number decreased in case of a heart
      overload reduction, and complete destruction of mitochondria and IMJ takes place
      in acute conditions leading to the animals' death of heart failure. The authors
      consider IMJ formation and destruction in pathology to be manifestation of the
      compensatory-adaptive reaction not described so far.

PMID- 9139594
TI  - [The effect of adrenoblockers on the ultrastructural changes in the epithelium
      and neural elements of the small intestine of suckling rabbits with experimental
      cholera].
AB  - Infant rabbits (10-12-day old) were infected with El Tor 5879 culture via
      stomach. During the period of cholera vibrio adhesion (within 4 hr) and twice on
      the following day the animals were injected intraperitoneally with alpha- and
      beta-adrenoblockers pyrroxan and obsidan. It was established that mono- or
      combined therapy with adrenergic blocking agents prevents the vibrio adhesion,
      cholera vibrios were detected mainly in the small intestine lumen. In addition,
      adrenoblockers arrest adenylate cyclase activation realized through cAMP
      formation and subsequent diarrhea development.

PMID- 9139595
TI  - [The sympathetic innervation of the myocardium and its damage in acute massive
      pulmonary embolism].
AB  - The state of the adrenergic heart innervation and injuries of right (RV) and left
      (LV) ventricles in experimental massive embolism of pulmonary arteries (MEPA)
      were studied in 62 dogs under conditions of the intact thorax and natural
      respiration. The degree of focal myocardial injuries depended upon the density of
      the sympathetic innervation: when the density of adrenergic nerves (AN) was high
      the number of injuries decreased. Hypercatecholaminemia developing at the early
      period of MEPA has a cardiotoxic effect, more pronounced in dogs with
      decompensation. A decrease of the AN density and increase of injuries in RV and
      LV were observed in long-term experiments. The results allow explaining the
      possibility of the adaptation processes breakdown by the development of heart
      failure in acute MEPA.

PMID- 9139596
TI  - [The effect of choleragen poisoning on the intestinal apudocytes of gnotobiotic
      minipigs].
AB  - Intragastric administration of the cholera toxin to gnotobiotic mini-pigs results
      in cyclic morphofunctional alterations of intestinal apudocytes followed by their
      degranulation, a decrease in their number from 1 to 3 hrs and after 18 hrs, while
      a slight increase in their number occurred from 3 to 12 hrs. The response of APUD
      system cells is similar in large and small intestine. Products of apudocyte
      secretion may be involved in the diarrheogenic effect of the cholera toxin.

PMID- 9139598
TI  - [Trace elements and natural killer activity].
AB  - Each cell of human body contains from 10(5) to 10(6) ions of different trace
      elements which may perform the important functions of regulation of cell
      metabolic system activity, genomic apparatus. However, the problem of trace
      elements influence on immune response, cytokine system, expression of components
      of the major histocompatibility complex and natural killer (NK) activity is not
      well studied. Some trace elements (Li, Zn, Mg, Se, Ge, Fe, etc.) show their
      effect on the level of intracellular messenger systems, inducing the production
      and potentiating the action of the great number of cell cytokines stimulating NK.
      Immune cytokines provide efficiency of NK-lysis and promote the decrease of tumor
      cell resistance to it. Interactions of trace elements and antitumor immunity is a
      perspective field of investigation.

PMID- 9139597
TI  - [Embolism of the small branches of the pulmonary artery in x-ray endovascular
      occlusion of the renal vessels in cancer].
AB  - The author reports a case of complication of chemoembolization of the kidney
      arterial bed used in the treatment of kidney carcinoma. The female patient died
      on the second day after the manipulation because of embolism of the small
      branches of the pulmonary artery by the particles of the embolisation mixture.
      The presence of the arterial-venous shunts in the tumor overlooked at the stage
      of angiography became the most probable cause of the embolism.

PMID- 9139599
TI  - [The immunocompetent structures of the skin and their role in the development of
      primary skin lymphomas].
AB  - Participation in immune reactions of main morphological skin structures
      (epidermal cells, skin associated lymphoid tissue, macrophagal and vascular
      systems) is described. Cooperation of these systems in immune reaction by means
      of complementary receptors on the cell membranes, adhesive molecules, cytokines
      and lymphokines is discussed. Primary malignant skin lymphomas are considered as
      tumors of the skin immune system.

PMID- 9139600
TI  - [Cancer and the regional lymph nodes (immunohistochemical and ultrastructural
      studies)].
AB  - 153 regional lymph nodes obtained during surgical operations because of cancer of
      various cites from 50 cancer patients were studied. Failure of local immunity is
      explained by the following factors: 1) depletion of T-cell population with a
      decrease of activated lymphocyte-killers; 2) high activity of B-cell population
      able to block T-cell cytotoxic effect; 3) deficiency of T-suppressors and T
      helpers; 4) a decrease of macrophages-monocytes of phagocytic capacity; 5) high
      activity of dendritic reticular cells stimulating transformation of B-lymphocytes
      and low activity of interdigitating reticulocytes determining T-cell immunity
      stimulation.

PMID- 9139601
TI  - [Morpho-immunologic phenotypes of T-cell non-Hodgkin's malignant lymphoma in
      baboons and their connection with with T-lymphotropic retrovirus STLV-1].
AB  - 8 cytological types were detected among 58 cases of T-NHL of Papio hamadryas
      according to human updated Kiel classification (1988). 5 of them were of low
      grade (lymphocytic, prolymphocytic, T-zone, angioimmunoblastic, small cell
      pleomorphic) and 3-of high grade (medium and large cell pleomorphic,
      immunoblastic, large cell anaplastic CD30/Ki-1+). There are differences in a
      tumor structure and generalization in baboon and human lymphomas in spite of
      significant similarities. STLV-1 presence (antibodies in blood and virus genome
      fragments in the lymphoma cell DNA) detected by PCR-amplification in 7
      investigated types of baboon T-NHL. CD4+ immune phenotypes were predominant in T
      cell baboon lymphomas, while CD8+ phenotypes were rare. Abnormal phenotypes in
      some cases were also detected in the three-color FACS-analyses.

PMID- 9139602
TI  - [Nucleolar organizer regions and mitotic activity in non-Hodgkin's lymphoma].
AB  - Evaluation of nucleolar organizer regions (Ag-NOR) and mitotic regimen (MR) of
      normal lymph nodes and those with follicular hyperplasia (n = 10) as well as non
      Hodgkin's lymphomas (NHL) of low and high grade of malignancy (n = 40) is
      performed in 50 cytograms stained after Pappenheim and with colloidal silver.
      Correlation of indices of MR and Ag-NOR with morphologic grade of malignancy of
      NHL was found. For blastic forms of NHL higher Ag-NOR, lager number of mitoses
      and their pathologic forms are characteristic compared with cytic ones (8.59 +/-
      3.15; 13.60 +/- 4.9/1000; 37.9% and 2.06 +/- 0.63; 2.10 +/- 2.45/1000; 23.8%,
      respectively, p < 0.001). Calculation of Ag-NOR allowed to distinguish NHL of low
      grade and high grade of malignancy containing 1.13 to 3.68 and 4.76 to 18.22 Ag
      grains per nucleus, respectively (the difference is statistically significant).
      This is important for differential diagnosis of "small cell" types of the tumor.
      Significant correlation between the number of Ag-NOR and mitotic activity of NHL
      is found (r = 0.772; p < 0.001) indicating that the number of Ag-NOR reflects
      cell kinetics of the tumor. The results of the activity evaluation of Ag-NOR and
      MR of cells may be used in differential diagnosis, gradation and definition of
      proliferative NHL status.

PMID- 9139603
TI  - [Epidemiology in the study of problems of health and disease (lecture)].
AB  - Three population approaches are distinguished: statistical, clinical,
      epidemiological. Literature material on "etiological and epidemiological causes",
      "essential and sufficient causes", "internal and external etiological factors"
      "statistical and cause-effect relationship", etc. is summarised.

PMID- 9139604
TI  - [Proliferating cell nuclear antigen in precancerous cervical disease].
AB  - Monoclonal antibodies PC-10 were used to study the expression of PCNA in
      precancerous pathology of the uterine cervix in 50 biopsies in the presence of
      papilloma virus infection (PVI). Positive reaction was in 100% PVI before
      treatment; weak proliferative activity was in 40% and strong reaction in 15%. If
      PVI was complicated with degree III dysplasia, there was an increase of
      proliferative activity. The positive reaction was retained after the therapy in 4
      cases of the recurrent PVI. Positivity with PC-10 may be an unfavourable
      prognostic criterium.

PMID- 9139605
TI  - [Controversial aspects of verification and classification of thyroid tumors].
AB  - 20-year experience in the intraoperative study of more than 3000 goiters led the
      authors to the conclusion that the most correct verification of the pathologic
      process may be performed only by means of intraoperative stereomorphological and
      histotopographic examination of the biopsy. In case of nodular hyperplasia of
      follicular and macropapillary structures the most adequate term is adenomatous
      goiter. The term borderline thyroid tumor is also suggested although it needs
      further discussion by both clinicians and morphologists.

PMID- 9139606
TI  - [Radiation pathomorphism after a single large-fractionated preoperative
      irradiation of rectal cancer (electron microscopic study)].
AB  - Results of combined treatment of 113 patients with colon carcinoma receiving a
      single irradiation (7.5 Gy) before the operation were analysed. The single
      irradiation was well tolerated by all the patients without complications during
      the operation and in the postoperative period. It is found at the ultrastructural
      level that from 70 to 85% of the cells in the tumors removed were irreversibly
      damaged.

PMID- 9139607
TI  - [Morphologic characterization of the contemporary dysentery caused by Shigella
      flexneri 2A].
AB  - There is a tendency in St. Petersburg since 1990s to an increase of dysentery
      morbidity and lethality mainly caused by Flexner Shigella 2a. Morphology of the
      disease in adults is given on the material of 286 necropsies in 1993-1994 in the
      S. P. Botkin Infectious Hospital. Males (mean age 50 years) and among them
      chronic alcoholics prevailed; females (mean age 70 years) were frequently with a
      grave cardiovascular pathology. Advanced inflammation (fibrinous, ulcerative and
      hemorrhagic) of all colon and distal part of the small bowel was a common
      finding. Hemorrhagic infarctions of the ileum which were not described so far
      were observed in 10% of the cases.

PMID- 9139608
TI  - [Ultrastructure of the sympathetic ganglia in hypoxia].
AB  - Short-term hypoxia produces ultrastructural alterations in ganglions of rats in
      the form of dilatation of some membrane neuron compartments and sinuous plasmatic
      membrane. More long-term hypoxia produces structural changes of membrane cell
      components. An increase of lysosome number and lipofuscin granules alternations
      in chronic hypoxia (1 year) are similar to the age changes and are characterized
      by intensive accumulation of lipofuscin and Nissl bodies hypertrophy.

PMID- 9139609
TI  - [Immunohistochemistry characterization of neurocytoma of the cerebral
      hemispheres].
AB  - Neurocytoma accounts for 0.5% of all tumors of the central nervous system. 18
      such tumors are described. Homogeneous expression of neuron-specific enolase and
      synaptophysin and heterogeneous expression of PCNA and some proteins are
      characteristic for these tumors. Two immunophenotypic variants are distinguished:
      p30-32 positive tumors with high values of PCNA; c-er B-2 HSPh-highly positive
      variant with lower indices of the "growth fractions".

PMID- 9139610
TI  - [Cancer of the sebaceous gland and precancerous Pinkus fibroepithelioma of the
      anterior abdominal wall].

PMID- 9139611
TI  - [Profuse gastric bleeding in a female with Dieulafois syndrome].
AB  - Dieulafois syndrome is a rare congenital pathology with profuse gastric bleeding
      due to the damage to arterial wall in the submucosa layer. The case illustrates
      difficulties encountered in the treatment of such patients.

PMID- 9139612
TI  - [Boris Stepanovich Khominskii (100th anniversary of his birth)].

PMID- 9139613
TI  - [Cellular oncogenes and antioncogenes in thyroid tumors].
AB  - Analysis of literature indicates that genetic mechanisms of thyroid tumor
      development are connected with two main classes of genes: oncogenes whose
      activation may stimulate tumor growth and anti-oncogenes which acquire oncogenic
      properties due to the loss of their function through point mutation or deletion.
      Protooncogene Ras mutation plays a role in the early events in tumor development.
      Restructuration of Ret and Trk oncogenes, overexpression of Met and Ras point
      mutations are characteristic for papillary thyroid carcinoma.

PMID- 9139614
TI  - [Etiology and pathogenesis of stomach cancer].

PMID- 9139615
TI  - [Problems of ethics, deontology and esthetics in pathology practice].
AB  - Relationships between pathologists on the one hand and clinicians, patients
      asking for histological slides, relatives of the deceased persons on the other
      are extremely complicated and need special attention. Pathology service should
      not be considered as second-rate. Ethic problems in the pathology service are not
      yet properly dealt in the literature.

PMID- 9139616
TI  - [Lead--an etiologic factor in vascular disease: main evidence (lecture)].
AB  - Review of the literature showing that lead is one of the most potent etiological
      stimuli in the development of the characteristic vascular pathology (vasculitis,
      atherosclerosis, arteriosclerosis, arterial hypertension). The attempt is made to
      summarise sparse data on the routes and mechanisms of the lead vascular damage
      pathogenesis.

PMID- 9139617
TI  - Low-density lipoprotein adsorption for arteriosclerotic patients.
AB  - A wide variety of treatments is now available for arteriosclerosis obliterans
      (ASO) patients, not very successful in some cases. Low-density lipoprotein (LDL)
      apheresis using an extracorporeal adsorption column containing dextran sulfate
      cellulose beads was applied to control lipid levels intensively in ASO patients
      with accompanying drug-resistant hyperlipidemia. A series of the apheresis
      procedures had a remarkable impact on clinical symptoms and physiological
      findings with improvement in intermittent claudication observed in more than 80%
      of the patients. Improvements in plethysmogram and thermogram readings suggested
      an increased circulation in lower extremities in more than 80% of patients. In
      addition, the treatment improved blood rheology, as evidenced by a reduction in
      blood viscosity. In a follow-up study made by sending a questionnaire to
      previously treated patients it was revealed that improvements in clinical
      symptoms were well maintained even after cessation of the treatment. In
      conclusion, LDL apheresis proved to be a useful therapeutic tool in ASO patients
      having elevated lipid levels.

PMID- 9139618
TI  - Heparin-induced extracorporeal low-density lipoprotein precipitation and low
      density lipoprotein chemoadsorption onto dextran sulfate: a comparison.
AB  - Both heparin-induced extracorporeal low-density lipoprotein precipitation (HELP)
      and dextran sulfate (DS) apheresis are potent tools for acute and long-term risk
      factor reduction in the secondary prevention treatment of coronary patients
      suffering from recalcitrant hypercholesterolemia. They combine high efficacy and
      selectivity of risk factor removal. Whereas LDL cholesterol and lipoprotein (a)
      adsorption onto DS offers the advantage of an unlimited treatable plasma volume
      and somewhat easier handling, HELP reduces fibrinogen more effectively and does
      not interfere with angiotension-converting enzyme (ACE) inhibitors. Both systems
      can improve blood rheology and induce regression or stabilize coronary lesions.
      In an uncontrolled trial, HELP reduced the incidence of myocardial infarction. To
      date, no controlled prospective trials have been performed comparing the two
      systems with respect to their long-term risk factor reduction and their effect on
      coronary lesions, morbidity, and mortality.

PMID- 9139619
TI  - Extracorporeal removal of lipids by dextran sulfate cellulose adsorption.
AB  - Extracorporeal removal of low-density lipoprotein (LDL) cholesterol by dextran
      sulfate adsorption is indicated in patients with diet and drug resistant hyper
      cholesterolemia to prevent or to regress coronary heart disease. Plasma
      separation is the first step in the process, followed by adsorption of LDL
      cholesterol and lipoprotein (a) (Lp[a]) to negatively charged dextran sulfate
      covalently bound to cellulose beads. The reduction per treatment in LDL
      cholesterol is 65-75% and in Lp(a) 40-60%. In most patients one treatment per
      week is sufficient to reduce mean LDL to 100-150 mg/dl. Minor side effects occur
      in 2-6% of treatments. Major side effects are rare. In uncontrolled studies long
      term treatment was associated with inhibition of progression and induction of
      regression of coronary artery disease. LDL apheresis by dextran sulfate may
      increase blood perfusion of some tissues, and preliminary results indicate a
      beneficial effect on therapy resistant nephrotic syndrome with
      hypercholesterolemia.

PMID- 9139620
TI  - Treatment of severe hyperlipidemia: six years' experience with low-density
      lipoprotein apheresis.
AB  - In total, 30 patients suffering from familial hypercholesterolemia, resistant to
      diet and lipid-lowering drugs, were treated for up to 6 years (3.6 + or - 1.6;
      range, 0.2-6.8 years) with low-density lipoprotein (LDL) apheresis. Three
      different systems were used; the dextran sulfate adsorption system (Kaneka) for
      27 of 30 patients, the immunoadsorption system from Baxter for 2 of 30 patients,
      and the immunoadsorption system with special lipoprotein(a) (Lp[a]) columns from
      Lipopak for one patient. Prior to the LDL apheresis, 23 of 30 patients suffered
      from coronary heart disease. Twenty of 23 patients suffered intermittently from
      symptoms of angina, excertional dyspnea, and claudication. With LDL apheresis,
      reductions of 47% for total cholesterol, 49% for LDL, 26% for Lp(a), and 40% for
      triglycerides were reached. Severe side effects such as shock or allergic
      reactions were very rare (0.55%). In the course of treatment with LDL apheresis,
      an improvement in general well-being and increased performance were experienced
      in 27 of 30 patients. A reduction of nitrate medication between 60 and 100% was
      observed in 17 of 23 patients. The present data clearly demonstrate that
      treatment with LDL apheresis in patients suffering from severe familial
      hyperlipidemia, resistant to maximum conservative therapy, is very effective and
      safe even over long periods of time.

PMID- 9139621
TI  - Low-density lipoprotein apheresis in the treatment of two patients with coronary
      heart disease and extremely elevated lipoprotein (a) levels.
AB  - Hyperlipidemia and elevated lipoprotein (a) (Lp[a]) levels have been linked to
      the development and progression of premature atherosclerosis. Our study concerned
      2 white male patients (aged 36 and 42 years) with heterozygous familial
      hypercholesterolemia and extremely elevated Lp(a) concentrations that were
      resistant to diet regimens and lipid-lowering drugs. The patients were treated
      with low-density lipoprotein (LDL) apheresis for 59 months (Liposorber system,
      Kaneka, Japan) and 19 months (immunoadsorption system, special Lp(a) columns;
      Lipopak; Pocard, Russia), respectively. The concentration of Lp(a) decreased on
      average by 50%, total cholesterol by 27%, LDL cholesterol by 41%, triglycerides
      by 43%, and fibrinogen by 16%. High-density lipoprotein (HDL) cholesterol
      increased by approximately 4%. Before treatment with LDL apheresis, each patient
      had suffered 3 myocardial infarctions, and had had 4 and 6 coronary angiographies
      with 2 and 4 percutaneous transluminal angioplasties (PTCAs), respectively. Since
      treatment with LDL apheresis, no myocardial infarctions or cardiac complaints
      were observed. In the course of treatment, both patients reported an increased
      performance. Available data suggest that LDL apheresis may be effective in the
      treatment of patients, the only risk factor for premature atherosclerosis being
      extremely elevated Lp(a) concentrations.

PMID- 9139622
TI  - Low-density lipoprotein hemoperfusion using a modified polyacrylate adsorber: in
      vitro, ex vivo, and first clinical results.
AB  - Current lipid apheresis techniques can remove low-density lipoprotein (LDL)
      cholesterol only from plasma, i.e., a primary cell-plasma separation step is
      mandatory. This article describes in vitro, ex vivo, and clinical results using a
      new LDL adsorber compatible with human whole blood. It consists of modified
      polyacrylate, the negative charges of which can interact with the positively
      charged protein B moiety of LDL, thus retaining these particles on the surface of
      the adsorber. After the efficacy and selectivity of LDL removal had been
      demonstrated in vitro and ex vivo, a clinical pilot study corroborated these
      results. Thus, treating 60 ml of blood per kilogram of body weight in a single
      session, LDL hemoperfusion reduced LDL cholesterol by 50%, lipoprotein (a) by
      17%, and triglycerides by 19% in 6 hypercholesterolemic patients. High-density
      lipoprotein cholesterol recovery amounted to 97%. In conclusion, LDL
      hemoperfusion holds great promise for the future.

PMID- 9139623
TI  - Low-density lipoprotein removal methods by membranes and future perspectives.
AB  - Since the application by Thompson et al. in 1975 of plasma exchange for the
      treatment of 2 patients with familial hyperlipidemia, plasma purification
      techniques for selective low-density lipoprotein (LDL) removal (i.e., LDL
      apheresis) have been developed and adopted for the management of this disease.
      Thermofiltration is one of the LDL apheresis systems that utilizes membrane
      techniques developed by Nose and Malchesky's group in 1985. This article reviews
      its rationale, in vitro studies, animal studies, and clinical investigation.
      Thermofiltration effectively and selectively removes LDL cholesterol while
      retaining in the plasma physiologically important macromolecules such as albumin
      and high-density lipoprotein (HDL) cholesterol. Based on the global view of the
      treatment of atherosclerosis by LDL apheresis, membrane techniques are as
      effective, safe, and simpler to apply than other methods. Additionally, these
      methods are effective for the removal of lipoprotein (a) and fibrinogen; thus,
      they can address the needs in these application areas.

PMID- 9139624
TI  - The Lupus Plasmapheresis Study Group: rationale and updated interim report.

PMID- 9139625
TI  - Rate adaptive pacemakers.

PMID- 9139626
TI  - [Results of behavioral investigations of broilers kept on various litter
      materials].
AB  - Behavioural investigations by the help of time-sampling-method with broilers kept
      on different litter materials (wood chip deep litter with or without mixing,
      straw resp.) in 5 rounds (per round investigated: 5 days x 8 hours x 12 values/hr
      x 10 broilers = 24000 behavioural data) showed no evident differences between
      keeping systems which could lead to preferring or rejecting a system. A lower
      frequency of scratching and ground pecking and a higher percentage of comfort
      behaviour was found in broilers kept on straw because of increasing amount of
      faeces and compression of litter material. From the view point of ethology and
      animal hygiene wood chip deep litter system without mixing and a 10 cm layer of
      new wood pieces after every round could be recommended if economical aspects
      allow.

PMID- 9139627
TI  - [Investigations on the endoparasitic fauna of domestic cats in eastern
      Brandenburg].
AB  - The internal organs of 155 cats originating from 3 different territories in the
      eastern part of Brandenburg state were examined for parasites between 1993 and
      1995. Parasites were found in 85% of cats. Parasites with the highest prevalence
      were Toxocara mystax (45%), Hydatigera taeniaeformis (22%), Ancylostoma
      tubaeforme (17%) and Opisthorchis felineus (16%). Metorchis bilis, Mesocestoides
      spp., Taenia pisiformis, Capillaria plica, Capillaria sp., Ollulanus tricuspis,
      Aelurostrongylus abstrusus, Cystoisospora spp. and Sarcocystis spp. were
      diagnosed with a lower frequency. The occurrence of H. taeniaeforme, A.
      tubaeformis und O. felineus was depending on the origin of the cats.

PMID- 9139628
TI  - [Adenovirus-induced pneumonia in two guinea pigs].
AB  - Two cases of a rare virus-induced disease of Guinea pigs are described. The
      animals had died because of a pneumonia. Large intranuclear viral inclusion
      bodies could be demonstrated in the endothelial cells of the lungs. In the second
      case inclusion bodies could be found additionally in macrophages of the spleen
      and in macrophages, hepatocytes and endothelial cells of the liver. By means of
      electron microscopy the virus could be specified as adenovirus.

PMID- 9139629
TI  - [Characterization of Rhodococcus equi isolates from horse and man].
AB  - In the present investigation 19 and 22 R. equi-cultures isolated from diseased
      horses and humans, respectively, could be correctly identified by their
      morphological, biochemical and serological properties. The rod-coccus life cycle
      appeared to be a common feature of almost all cultures investigated. The cultures
      were typeable with the typing system described by Prescott (1981). The
      predominant serotypes among the R. equi-isolates belonged to serotypes 1 and 2.
      Among the R. equi-isolates from horses haemagglutination-positive cultures were
      mainly found among isolates of serotype 1, those of serotype 2 were
      haemagglutination-negative. The R. equi-cultures isolated from humans showed no
      relation between serotype and haemagglutinating properties. Determination of
      antibiotic susceptibility revealed that all cultures were susceptible to
      erythromycin, gentamicin, imipenem, minocycline, neomycin, rifampicin,
      streptomycin and vancomycin, 71% and 75% were resistant or at least moderate
      susceptible to tetracycline and penicillin G, respectively. Almost all cultures
      were resistant to ceftazidime and most cultures were susceptible to cefotaxime.
      The cultures could be further characterized by restriction endonuclease digestion
      and pulsed field gel electrophoresis of their chromosomal DNA. After digestion
      with the restriction enzyme AsnI the resulting DNA-profile allowed a strain
      specific characterization.

PMID- 9139630
TI  - [Cyclosporin A in aplastic anemia in dogs: first results].
AB  - Aplastic anemia in the dog is defined as a reduction of marrow activity
      comprising all three marrow cell lines or selectively of the erythropoiesis. In
      comparable cases in human medicine an immunogenic etiology is presumed, and a
      treatment with the immunosuppressant Cyclosporin A is initiated. There are no
      experiences with this kind of therapy in aplastic anemia of the dog. Four dogs,
      three with a hypoplasia of the erythropoietic cell line and one with
      panmyelophthisis, were treated orally for a period of several months with
      Cyclosporin A 5-10 mg/kg bodyweight bid. In all patients the plasma concentration
      of Cyclosporin was controlled in regular intervals. Depending on the plasma
      concentrations the dose was adapted in several cases. Cyclosporin levels between
      200 and 600 ng/ml were considered desirable and their efficacy in the therapy of
      aplastic anemia was examined. In the patient with panmyelophthisis, therapy was
      not successful. In this case, a marrow intoxication was presumably responsible
      for the aplastic anemia and the dog was euthanized. In two of the remaining three
      cases, therapy with Cyclosporin A was successful; the last dog is still being
      treated with Cyclosporin A at this time.

PMID- 9139631
TI  - [Investigations on the red blood cell count in mother sows].
AB  - Investigations have been conducted to the factors which have influence on the red
      blood count in postparturient sows. 147 blood samples of sows have been collected
      for the analysis of the influence of the number of lactations and puerperal
      diseases and 87 samples out of the collected blood samples were of healthy sows
      used to the analysis for the influence of the week of lactation. With rising
      number of lactations decrease the number of erythrocytes, packed cell volume and
      haemoglobin concentration, whereas mean corpuscular volume and mean corpuscular
      haemoglobin concentration rise. No significant changes of red blood count occur
      in the course of lactation. The number of erythrocytes and the packed cell volume
      decrease due to puerperal diseases. Hematological values of healthy
      postparturient sows are: erythrocytes: 5.8 +/- 0.6 T/l; packed cell volume: 0.41
      +/- 0.03 l/l; hemoglobin concentration: 7.64 +/- 0.67 mmol/l; mean corpuscular
      volume: 71.4 +/- 5.8 fl; mean corpuscular hemoglobin: 1.30 +/- 0.9 fmol; mean
      corpuscular hemoglobin concentration: 18.3 +/- 0.8 mmol/l.

PMID- 9139632
TI  - Circadian locomotor activity of Musca flies: recording method and effects of 10
      Hz square-wave electric fields.
AB  - Musca domestica flies that were exposed to a uniform vertical 10 Hz electric
      square-wave field of 1 kVm(-1) changed the period length of their circadian
      locomotor activity rhythm. Under constant conditions, the clock of short-period
      flies was slowed down by the field, whereas the clock of long-period flies either
      was affected only scarcely (experiments at about 19 degrees C) or ran faster
      (experiments at 25 degrees C). If the field was applied for only 12 h daily, then
      30-40 percent of the flies were synchronized. Thus, the field could function as a
      weak "Zeitgeber" (synchronizer). If the field was increased to 10 kVm(-1), then
      50-70 percent of the flies were synchronized. Flies avoided becoming active
      around the onset of the 12 h period of exposure to a 10 Hz field. The results of
      these experiments are discussed with respect to similar experiments by Wever on
      the effects of exposure to a 10 Hz field on the circadian system of man.

PMID- 9139633
TI  - Evaluation of potential health effects of 10 kHz magnetic fields: a short-term
      mouse toxicology study.
AB  - A high-frequency inductive power distribution (HID) technology has been developed
      that generates sinusoidal magnetic fields at a frequency of 10 kHz. In typical
      industrial applications, field intensities in the order of 0.2 mT can be expected
      between the current-carrying coils. Because the possible health effects of 10 kHz
      sinusoidal magnetic fields of this type had never been investigated, a broad
      evaluation of possible effects on animal health was made in a preliminary 14 day
      acute study and in a 90 day subchronic study using male and female B6C3F1 mice.
      Exposures were at 0.08, 0.28, and 1.0 mT vs. a background exposure of 3.7 microT
      and were essentially continuous. These studies failed to demonstrate any health
      effects that can be clearly related to the magnetic field exposure. No changes in
      animal behaviour or indications of morbidity were detected during the initial
      exposure to the fields. There were no significant differences in body weight
      between exposed and unexposed (control) mice at any time in the study, and the
      clinical chemistry and hematology parameters were essentially unchanged. Although
      minor differences in some clinical chemistry and hematology parameters were seen
      between control and exposure groups, the lack of exposure dependence, the lack of
      consistency between sexes, and the lack of correspondence with the results of the
      two studies all suggest that these were chance associations. Even if the changes
      were real, the magnitude of the changes was very small and does not indicate
      serious biological effects. Finally, all organs were macroscopically and
      microscopically normal except for isolated, generally mild, histological lesions
      and lesions that were ascribed to fighting among males. There was no obvious
      association with field intensity.

PMID- 9139634
TI  - Comment on "Acute low-intensity microwave exposure increases DNA single-strand
      breaks in rat brain cells" by Henry Lai and Narendra P. Singh.

PMID- 9139635
TI  - Managing electromagnetic fields from residential electrode grounding systems: a
      predecision analysis.
AB  - Several epidemiological studies have linked exposure to electromagnetic fields
      (EMFs) with health effects, including leukemia and brain cancer, but the research
      is still inconclusive. In particular, no clear causal mechanism has been
      identified by which EMFs may promote cancers. Nevertheless, the concerns raised
      by the positive epidemiological studies have led to increasing efforts to reduce
      EMFs from a number of sources. One source of EMFs are home grounding systems that
      are connected through water pipes in homes to water mains. This paper analyzes
      whether home owners who are concerned about electromagnetic fields exposure from
      home grounding systems should take any action to reduce fields. Assuming that the
      grounding system produces elevated magnetic fields (e.g., 2-3 mG or higher), this
      study investigates several readily available alternatives and evaluates them with
      respect to five criteria: risk reduction, cost, fire risk increase, worker risk,
      and electrical shock risk. Because of the lack of conclusive evidence about an
      EMF-cancer relationship, this study uses a parameterized approach that makes
      conditional estimates of health risk depending on future research outcomes and on
      the nature of the EMF/health effects relationship. This type of analysis, which
      is called predecision analysis because of its preliminary nature, is therefore
      highly dependent on a set of assumptions. Nevertheless, this predecision analysis
      had some fairly clear results. First, waiting for more research or taking a
      fairly inexpensive corrective action (insulating the water pipe to reduce ground
      current flow) seem to be the main contenders for the best decision for many
      different assumptions and parameters. Second, the choice between these two
      actions is very sensitive to variations in assumptions and parameters. Homeowners
      who accept the base-case assumptions and parameters of this study should prefer
      to wait. If any of the base-case parameters are changed to more pessimistic
      estimates or if psychological concerns (like worry and regret) are considered,
      then the best action is to insulate the pipe to reduce the current flow through
      the water pipes.

PMID- 9139636
TI  - Resection of meningiomas with implantable microwave coagulation.
AB  - Implantable microwave coagulation was used to perform resection on 62 patients
      that had intracranial meningiomas. When 20-60 W microwave power was applied for
      15 s, the temperature at the center of the tumor tissue was 43-63 degrees C; 30
      mm from the center, the temperature was under 40 degrees C. Histological changes
      in the center of the tumor showed coagulative necrosis, diminished nuclei, and
      obliterated blood vessels. The changes at 10-20 mm from the center of the tumor
      showed coagulative necrosis and degeneration and, 30-50 mm from the center of the
      tumor, showed normal cell morphology after microwave coagulation. The thermal
      field in brain tumor has an effective diameter of about 40 mm. No side effects on
      the normal brain tissues were observed. The amount of blood loss during the
      operation was minimal while the meningioma was coagulated, especially when the
      meningioma was located at the skull base or in the parasagittal or cerebral
      convexity region. After microwave coagulation, the entire tumor could easily be
      removed. Among the 62 surgically treated cases, gross total tumor excision was 85
      percent. No postoperative complications occurred after microwave coagulation, and
      there was no operative mortality in the series. We believe that this new
      technique has the advantage of simplicity, less blood loss, and smooth
      postoperative procedures. Hemostatic effects during the operation are
      satisfactory, and blood transfusion can be reduced by 50-60 percent.

PMID- 9139637
TI  - Lorentz approach to static magnetic field effects on bound-ion dynamics and
      binding kinetics: thermal noise considerations.
AB  - The present study characterizes an ion-binding site, a molecular cleft in a
      signalling molecule such as calmodulin or troponin C, as a damped linear
      isotropic oscillator potential for small displacements about the origin.
      Quantitative assessments of the effects of thermal noise and exogenous static
      magnetic fields are made through a statistical mechanical treatment of the
      Lorentz-Langevin equation for an ion bound in a molecular cleft. Thermal noise
      causes a bound ion to be ejected from the site after a bound lifetime dependent
      upon the thermal noise spectral density. It is shown that the Lorentz-Langevin
      model requires values of the viscous damping parameter many orders of magnitude
      below those for bulk water in order to characterize the binding site and to
      obtain realistic lifetimes for a bound ion. The model predicts that milliTesla
      range magnetic fields are required for static field effects on dissociation
      kinetics. The Lorentz equation also yields a classic coherent solution describing
      precession of the bound-ion oscillator orientation at the Larmor frequency. The
      bound-ion dynamics described by this coherent solution are sensitive to
      microTesla-range static magnetic fields in the presence of thermal noise.
      Numerical integration of the contribution of thermal noise forces to these
      dynamics is in good agreement with the results of statistical mechanical
      analysis, also producing realistic bound lifetimes for only very low viscous
      damping values. The mechanisms by which modulation of precessional motion might
      enable a signalling molecule such as calmodulin to detect an exogenous magnetic
      field are presently unclear.

PMID- 9139638
TI  - [Integration of IS186 element into the -10-region of the promoter of heat shock
      lon-gene in Escherichia coli].
AB  - The insertion element IS186 was found to be incorporated into the -10 region of
      the promoter of the E. coli lon gene. The integration represses lon gene
      expression. Homology between the integration sites of IS186, the -10 region of E.
      coli heat shock promoters, and the terminal inverted repeat of IS186 was
      revealed.

PMID- 9139639
TI  - [Study of the secondary structure of a single-stranded DNA fragment using self
      modification reaction].
AB  - Electrophoretic analysis of the products of chemical destruction at modified base
      residues was used to determine the site-directedness of self-alkylation of the 26
      mer DNA fragment pTTGCCTTGAATGGGAAGAGGGTCATT (T26). This fragment possesses a 4
      [N-methyl-N-(2-chloroethyl)amino]benzylamido group (CIR-), covalently attached to
      the 5'-terminal phosphate group both in the presence and in the absence of the
      oligonucleotide effector (Phn-L)pTGACCCTCp(L-Phn), where Phn is an N-(2
      hydroxyethyl)phenazinium residue and L is an ethylenediamine linker. Molecular
      modeling with the method of molecular mechanics/dynamics (MM/D) was used to
      investigate the secondary structure of the CIR-T26 conjugate and to interpret the
      change of the alkylation site upon treatment with CIR-T26 in the presence of an
      effector.

PMID- 9139640
TI  - [Gene-directed biologically active substances (antisense oligonucleotides and
      their derivatives)].
AB  - Results of studies carried out over the last eight years under the Russian State
      Scientific and Technical Program "New Methods in Bioengineering" are reviewed.
      New addressing constructions formed by a tandem of two or more oligonucleotides
      on a target nucleic acid are described. The reactivity of the tandem is enhanced
      due to the stabilization of some components, either by attachment of polyaromatic
      systems (method of effectors) or by the formation of a reaction center, which
      occurs when the components of the active center draw together into a tandem.
      Reagents which are oligonucleotide derivatives are also described, in particular
      a derivative of the antibiotic bleomycin, which is capable of catalytic cleavage
      of the target. Evidence is presented that oligonucleotides interact with the
      proteins of cells and living organisms, including the receptor proteins
      discovered in the course of this research, the T-helper CD4 receptor,
      immunoglobulins, and some growth factors.

PMID- 9139641
TI  - [Novel reagent for labeling of biomolecules--activated derivative of pyrene
      dichromophore with excimeric fluorescence].
AB  - N-[2-(1-pyrenyl)ethyl]-1-pyrenylacetamide, bis[2-(1-pyrenyl)ethyl]amine, and N,N
      bis[2-(1-pyrenyl)ethyl]succinamide were synthesized from 1-pyrenylacetic acid.
      These compounds contain adjacent pyrene residues and display excimer
      fluorescence. The latter compound, as a pentafluorophenyl ester, was used to
      prepare fluorescently labeled oligodeoxyribonucleotide (5)CAGGAAACAGCTATGAC. For
      N,N-bis[2-(1-pyrenyl)ethyl]succinamide, the excimer-to-monomer fluorescence ratio
      and intensity of fluorescence in water-methanol solutions changed in the presence
      of single-stranded and double-stranded oligonucleotides, upon attachment to an
      oligonucleotide, and upon hybridization of the resulting conjugate with the
      complementary nucleotide sequence.

PMID- 9139642
TI  - [Ribonucleoside-5'-monophosphates with disubstituted phosphate residue do not
      interact with human inosine monophosphate dehydrogenase].

PMID- 9139643
TI  - [Solid phase synthesis of beta amyloid (1-42)].
AB  - A solid phase synthesis of the polypeptide corresponding to the 1-42 sequence of
      beta-amyloid protein that accumulated in brain cells during Alzheimer's disease
      was performed using Fmoc strategy. Two alternative approaches to the synthesis,
      stepwise elongation of the peptide chain and fragment coupling, were compared,
      and the advantage of the latter approach was shown. Effects of various factors
      (solvents, reagents for deprotection of alpha-amino functions, and substitution
      level of polymer carrier) on the synthesis was studied. The appropriate
      conditions of HPLC for an analysis of the homogeneity of the beta A4(1-42)
      peptide, as well as the conditions of its gel chromatography on Sephadex G-50
      providing the preparation of the end product of 90-95% purity according to HPLC
      were found.

PMID- 9139644
TI  - [Gel filtration of protected synthetic peptides in dimethylformamide].
AB  - For large water-insoluble protected peptides, a novel method of analytical and
      preparative size exclusion liquid chromatography on Toyopearl HW-40, HW-50, HW
      55, and HW-60 gels was proposed, with DMF as an eluent. The selectivity and
      molecular mass ranges of these gels were determined for separation of protected
      peptides in DMF. The molecular mass ranges of Toyopearl HW gels for protected
      peptides in DMF were found to differ significantly from those for peptides and
      proteins in aqueous buffer solutions.

PMID- 9139645
TI  - [Synthesis of terminal disaccharide of Forssman antigen and its analogs as spacer
      glycosides and free disaccharides].
AB  - Spacered terminal disaccharide of Forssman's antigen GalNAc alpha 1-3GalNAc beta
      1-Osp, its analog GalNAc alpha 1-3GalNAc alpha 1-Osp, and disaccharides Gal beta
      1-3GalNAc beta 1-Osp and Gal alpha 1-3GalNAc alpha 1-Osp [where sp denotes the
      (CH2)3NHCOCF3 spacer] were synthesized. Spacered disaccharides were obtained from
      the (3-trifluoroacetamidopropyl)-2-acetamido-4,6-O-benzylidene-2-deoxy-beta-D-
      galactopyranoside and its alpha- and beta-analogs in which the 2-azido group was
      substituted for the 2-acetamido group. The azide glycosyl acceptors gave higher
      yields of the disaccharides. Azide glycosyl acceptors were prepared by the
      stereoselective glycosylation of 3-trifluoroacetamidopropanol with a mixture of 1
      O-acetates of the 2-azido-3,4,6-tri-O-acetyl-2-deoxy-D-galactopyranose anomers in
      the presence of Lewis acids. Disaccharides Gal alpha 1-3GalNAc and GalNAc alpha 1
      3GalNAc were obtained from the benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-alpha
      D-galactopyranoside.

PMID- 9139646
TI  - [Acylation of 3beta-(2-hydroxyethoxy)cholest-5-ene in the presence of
      lecithin:cholesterol acyltransferase from blood plasma].
AB  - 3 beta-(2-Hydroxyethoxy)cholest-5-ene in the composition of the micellar
      complexes with apolipoprotein A1 and palmitoyloleoylphosphatidylcholine was
      acylated in the presence of lecithin-cholesterol acyltransferase from human
      plasma. The initial rate of acylation was 6-8 times lower than the rate of
      cholesterol acylation under the same conditions. The presence of 3 beta-(2
      hydroxyethoxy)cholest-5-ene did not affect the rate of the enzymic acylation of
      cholesterol.

PMID- 9139647
TI  - [Cytokine receptors: functional asymmetry of subunits in the receptor complex].

PMID- 9139648
TI  - Thermodynamics and kinetics of a Brownian motor.
AB  - Nonequilibrium fluctuations, whether generated externally or by a chemical
      reaction far from equilibrium, can bias the Brownian motion of a particle in an
      anisotropic medium without thermal gradients, a net force such as gravity, or a
      macroscopic electric field. Fluctuation-driven transport is one mechanism by
      which chemical energy can directly drive the motion of particles and
      macromolecules and may find application in a wide variety of fields, including
      particle separation and the design of molecular motors and pumps.

PMID- 9139651
TI  - Polarization-enhanced NMR spectroscopy of biomolecules in frozen solution.
AB  - Large dynamic nuclear polarization signal enhancements (up to a factor of 100)
      were obtained in the solid-state magic-angle spinning nuclear magnetic resonance
      (NMR) spectra of arginine and the protein T4 lysozyme in frozen glycerol-water
      solutions with the use of dynamic nuclear polarization. Polarization was
      transferred from the unpaired electrons of nitroxide free radicals to nuclear
      spins through microwave irradiation near the electron paramagnetic resonance
      frequency. This approach may be a generally applicable signal enhancement scheme
      for the high-resolution solid-state NMR spectroscopy of biomolecules.

PMID- 9139655
TI  - Modeling of cometary X-rays caused by solar wind minor ions.
AB  - X-ray emission was discovered in comet Hyakutake (C/1996 B2) by the Rontgen
      satellite in 1996, and these emissions were attributed to the excitation of high
      charge state solar wind ions due to electron capture from cometary molecules or
      atoms. Using the plasma flow in the coma of Hyakutake calculated by a three
      dimensional adaptive magnetohydrodynamic model, the density distribution of solar
      wind ions in the coma and the resulting x-ray emission were computed. The
      calculated High Resolution Imager count rate of 4.4 per second and the spatial
      distribution of the x-ray emission agree with the observations. A detailed energy
      spectrum of cometary x-rays is predicted in the 80 to 2000 electronvolt energy
      range. Cometary x-rays present a sensitive tool to monitor cometary activity and
      solar wind ion composition.

PMID- 9139656
TI  - A proficient enzyme revisited: the predicted mechanism for orotidine
      monophosphate decarboxylase.
AB  - A mechanism is proposed to explain the activity of orotidine 5'-monophosphate
      decarboxylase (ODCase). This enzyme is the one of the most proficient known, with
      a catalytic proficiency (kcat/Km)/knon = 10(23) M-1. Quantum mechanical
      calculations predict a mechanism involving a stabilized carbene intermediate,
      which represents a previously unrecognized mode of enzymatic activity for ODCase.
      The proposed mechanism involves proton transfer from a weak acid (pKa = 7, where
      Ka is the acid constant) concerted with decarboxylation, in a nonpolar enzyme
      environment. Such a mechanism makes possible different approaches to the design
      of ODCase inhibitors. Furthermore, the prediction that general acid catalysis may
      only be effective in low dielectric media is of general significance for
      understanding the activity of many enzymes.

PMID- 9139658
TI  - A tonic hyperpolarization underlying contrast adaptation in cat visual cortex.
AB  - The firing rate responses of neurons in the primary visual cortex grow with
      stimulus contrast, the variation in the luminance of an image relative to the
      mean luminance. These responses, however, are reduced after a cell is exposed for
      prolonged periods to high-contrast visual stimuli. This phenomenon, known as
      contrast adaptation, occurs in the cortex and is not present at earlier stages of
      visual processing. To investigate the cellular mechanisms underlying cortical
      adaptation, intracellular recordings were performed in the visual cortex of cats,
      and the effects of prolonged visual stimulation were studied. Surprisingly,
      contrast adaptation barely affected the stimulus-driven modulations in the
      membrane potential of cortical cells. Moreover, it did not produce sizable
      changes in membrane resistance. The major effect of adaptation, evident both in
      the presence and in the absence of a visual stimulus, was a tonic
      hyperpolarization. Adaptation affects a class of synaptic inputs, most likely
      excitatory in nature, that exert a tonic influence on cortical cells.

PMID- 9139659
TI  - Regulation of protein phosphatase 2A by direct interaction with casein kinase
      2alpha.
AB  - Timely deactivation of kinase cascades is crucial to the normal control of cell
      signaling and is partly accomplished by protein phosphatase 2A (PP2A). The
      catalytic (alpha) subunit of the serine-threonine kinase casein kinase 2 (CK2)
      bound to PP2A in vitro and in mitogen-starved cells; binding required the
      integrity of a sequence motif common to CK2alpha and SV40 small t antigen.
      Overexpression of CK2alpha resulted in deactivation of mitogen-activated protein
      kinase kinase (MEK) and suppression of cell growth. Moreover, CK2alpha inhibited
      the transforming activity of oncogenic Ras, but not that of constitutively
      activated MEK. Thus, CK2alpha may regulate the deactivation of the mitogen
      activated protein kinase pathway.

PMID- 9139660
TI  - Structures of the tyrosine kinase domain of fibroblast growth factor receptor in
      complex with inhibitors.
AB  - A new class of protein tyrosine kinase inhibitors was identified that is based on
      an oxindole core (indolinones). Two compounds from this class inhibited the
      kinase activity of fibroblast growth factor receptor 1 (FGFR1) and showed
      differential specificity toward other receptor tyrosine kinases. Crystal
      structures of the tyrosine kinase domain of FGFR1 in complex with the two
      compounds were determined. The oxindole occupies the site in which the adenine of
      adenosine triphosphate binds, whereas the moieties that extend from the oxindole
      contact residues in the hinge region between the two kinase lobes. The more
      specific inhibitor of FGFR1 induces a conformational change in the nucleotide
      binding loop. This structural information will facilitate the design of new
      inhibitors for use in the treatment of cancer and other diseases in which cell
      signaling by tyrosine kinases plays a crucial role in disease pathogenesis.

PMID- 9139661
TI  - Kinetics of response in lymphoid tissues to antiretroviral therapy of HIV-1
      infection.
AB  - In lymphoid tissue, where human immunodeficiency virus-type 1 (HIV-1) is produced
      and stored, three-drug treatment with viral protease and reverse transcriptase
      inhibitors markedly reduced viral burden. This was shown by in situ hybridization
      and computerized quantitative analysis of serial tonsil biopsies from previously
      untreated adults. The frequency of productive mononuclear cells (MNCs) initially
      diminished with a half-life of about 1 day. Surprisingly, the amount of HIV-1 RNA
      in virus trapped on follicular dendritic cells (FDCs) decreased almost as
      quickly. After 24 weeks, MNCs with very few copies of HIV-1 RNA per cell were
      still detectable, as was proviral DNA; however, the amount of FDC-associated
      virus decreased by >/=3.4 log units. Thus, 6 months of potent therapy controlled
      active replication and cleared >99.9 percent of virus from the secondary lymphoid
      tissue reservoir.

PMID- 9139662
TI  - Interactions between epithelial cells and bacteria, normal and pathogenic.

PMID- 9139664
TI  - Vigilin, a ubiquitous protein with 14 K homology domains, is the estrogen
      inducible vitellogenin mRNA 3'-untranslated region-binding protein.
AB  - RNA-binding proteins containing KH domains are widely distributed. One KH domain
      protein of unknown function, vigilin (also known as the high density lipoprotein
      binding protein), contains 14 KH domains and is ubiquitous in vertebrate cells.
      We previously used RNA gel mobility shift assays to describe an estrogen
      inducible protein which binds specifically to a segment of the 3'-untranslated
      region (3'-UTR) of vitellogenin mRNA, an area which has been implicated in the
      estrogen-mediated stabilization of vitellogenin mRNA. Here we show that the
      vitellogenin mRNA-binding protein (VitRNABP) is vigilin. The VitRNABP was
      isolated as a 150-155-kDa protein on a vitellogenin mRNA 3'-UTR affinity column.
      Peptide microsequencing revealed that the purified protein was vigilin, a
      conclusion confirmed in Western blot analysis with antibodies to vigilin. Direct
      confirmation that vigilin is the VitRNABP was obtained from RNA gel mobility
      shift assays which demonstrated that antibodies to chicken vigilin supershifted
      the Xenopus VitRNABP band. Xenopus liver vigilin mRNA and the VitRNABP exhibited
      similar induction by estrogen, providing additional confirmation that vigilin is
      the estrogen-inducible protein which binds to the 3'-UTR of estrogen-stabilized
      vitellogenin mRNA. These data support a role for vigilin in the hormonal control
      of mRNA metabolism.

PMID- 9139665
TI  - Interaction of phosducin-like protein with G protein betagamma subunits.
AB  - Phosducin-like protein (PhLP), a widely expressed ethanol-responsive gene (Miles,
      M. F., Barhite, S., Sganga, M., and Elliott, M. (1993) Proc. Natl. Acad. Sci. U.
      S. A. 90, 10831-10835), is a homologue of phosducin, a known major regulator of
      Gbetagamma signaling in retina and pineal gland. However, although phosducin has
      a well characterized role in retinal phototransduction, function of the PhLP
      remains unclear. In this study we examine the ability of PhLP to bind Gbetagamma
      dimer in vitro and in vivo. Using PhLP glutathione S-transferase fusion proteins,
      we show that PhLP directly binds Gbetagamma in vitro. Studies with a series of
      truncated PhLP fusion proteins indicate independent binding of Gbetagamma to both
      the amino- and C-terminal halves of PhLP. Protein-protein interactions between
      Gbetagamma and PhLP are inhibited by the alpha subunit of Go and Gi3, suggesting
      that PhLP can bind only free Gbetagamma. Finally, we show that PhLP complexes, at
      least partially, with Gbetagamma in vivo. Following overexpression of epitope
      tagged PhLP together with Gbeta1gamma2 proteins in COS-7 cells, a PhLP-Gbetagamma
      complex is co-immunoprecipitated by monoclonal antibody directed against the
      epitope tag. Similarly, polyclonal anti-PhLP antibody co-precipitates endogenous
      PhLP and Gbetagamma proteins from NG108-15 cell lysates. These data are
      consistent with the hypothesis that PhLP is a widely expressed modulator of
      Gbetagamma function. Furthermore, because alternate forms of the PhLP transcript
      are expressed, there may be functional implications for the existence of two
      Gbetagamma-binding domains on PhLP.

PMID- 9139666
TI  - Rho-associated kinase directly induces smooth muscle contraction through myosin
      light chain phosphorylation.
AB  - Small GTPase Rho plays pivotal roles in the Ca2+ sensitization of smooth muscle.
      However, the GTP-bound active form of Rho failed to exert Ca2+-sensitizing
      effects in extensively Triton X-100-permeabilized smooth muscle preparations, due
      to the loss of the important diffusible cofactor (Gong, M. C., Iizuka, K., Nixon,
      G. , Browne, J. P., Hall, A., Eccleston, J. F., Sugai, M., Kobayashi, S. ,
      Somlyo, A. V., and Somlyo, A. P. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 1340
      1345). Here we demonstrate the contractile effects of Rho-associated kinase (Rho
      kinase), recently identified as a putative target of Rho, on the Triton X-100
      permeabilized smooth muscle of rabbit portal vein. Introduction of the
      constitutively active form of Rho-kinase into the cytosol of Triton X-100
      permeabilized smooth muscle provoked a contraction and a proportional increase in
      levels of monophosphorylation of myosin light chain in both the presence and the
      absence of cytosolic Ca2+. These effects of constitutively active Rho-kinase were
      wortmannin (a potent myosin light chain kinase inhibitor)-insensitive. Immunoblot
      analysis revealed that the amount of native Rho-kinase was markedly lower in
      Triton X-100-permeabilized tissue than in intact tissue. Our results demonstrate
      that Rho-kinase directly modulates smooth muscle contraction through myosin light
      chain phosphorylation, independently of the Ca2+-calmodulin-dependent myosin
      light chain kinase pathway.

PMID- 9139667
TI  - Identification of a binding site in protease nexin I (PN1) required for the
      receptor mediated internalization of PN1-thrombin complexes.
AB  - An overlapping synthetic peptide library was constructed representing most of the
      mature protease nexin I (PN1) sequence from the amino terminus to the reactive
      center. This library, along with peptides from the heparin binding domain and
      from the region carboxyl-terminal to the P1 residue of the cleavage site, was
      screened for the inhibition of 125I-thrombin (Th)-PN1 complex binding and
      degradation. A peptide corresponding to residues Pro47-Ile58 in the PN1 sequence
      was identified as a potent inhibitor of 125I-Th-PN1 complex degradation, although
      it did not affect binding significantly. Pro47-Ile58 was shown to competitively
      inhibit the low density lipoprotein receptor-related protein (LRP)/alpha2
      macroglobulin receptor-mediated endocytosis of 125I-Th-PN1 complexes in mouse
      embryo fibroblasts. Pro47-Ile58 is an apparent transition sequence in PN1,
      separating sheet-6B and helix-B. The sequence of Pro47-Ile58, PHDNIVISPHGI,
      suggests that it forms a loop structure defined by the seven underlined amino
      acids bordered by proline residues at each end. These studies are the first to
      identify a putative binding site in a serine protease inhibitor that is required
      for LRP-mediated internalization.

PMID- 9139668
TI  - NusA is required for ribosomal antitermination and for modulation of the
      transcription elongation rate of both antiterminated RNA and mRNA.
AB  - Ribosomal RNA (rRNA) is elongated twice as fast as mRNA in vivo due to the
      presence of antitermination sequences in the 5' part of the rRNA transcripts. A
      number of Nus factors bind to RNA polymerase at the antitermination sites and
      help confer resistance to Rho-dependent termination of transcription. In this
      paper, the effects of the nusAcs10 allele on the elongation rate of both mRNA and
      antiterminated RNA were investigated. The results indicate that NusA is required
      to achieve a high elongation rate of RNA chains carrying the ribosomal
      antitermination boxA and that antitermination is defective when the rate of
      transcription elongation is decreased by the nusAcs10 allele. Furthermore, the
      nusAcs10 allele had no significant effects on the elongation rate of normal lacZ
      mRNA during steady state growth, but it abolished the inhibition of lacZ mRNA
      elongation by guanosine 3',5'-bis(diphosphate) (ppGpp). These results suggest
      that NusA is the component of the transcription elongation complex required for
      inhibition of mRNA elongation by ppGpp.

PMID- 9139669
TI  - Normal activity of microsomal triglyceride transfer protein is required for the
      oleate-induced secretion of very low density lipoproteins containing
      apolipoprotein B from McA-RH7777 cells.
AB  - The requirement of the activity of microsomal triglyceride transfer protein (MTP)
      for very low density lipoprotein (VLDL) secretion was determined using McA-RH7777
      cells stably transfected with human apoB48 (hB48). Secretion of VLDL containing
      hB48 (hB48-VLDL) by the transfected cells was induced by exogenous oleate (0.4
      mM), and oleate-dependent VLDL secretion was selectively inhibited by brefeldin A
      (0.2 microg/ml). Two protocols were used to determine the effect of MTP
      inhibition on VLDL secretion. In the first protocol, cell protein and lipid were
      labeled with radioactive amino acids and oleate prior to MTP inhibition (using 5
      microM of the photoaffinity inhibitor BMS-192951 to reduce MTP activity by 65
      70%), and secretion of prelabeled apoB and triacylglycerol (TG) associated with
      lipoproteins was monitored during oleate-supplemented chase. In control cells, a
      6-fold increase in incorporation of prelabeled TG into hB48-VLDL was observed
      after oleate supplement, while incorporation of prelabeled TG into VLDL
      containing endogenous rat apoB100 (rB100-VLDL) was unaffected. Inhibition of MTP
      activity abolished the oleate-induced utilization of prelabeled TG (by 80%) and
      hB48 (by 70%) for hB48-VLDL secretion but decreased utilization of pre-existing
      TG (by <25%) and B100 (by 45%) for rB100-VLDL secretion to a lesser extent.
      Inhibition of MTP did not affect incorporation of prelabeled TG or hB48 into high
      density lipoproteins containing hB48 (hB48-HDL). In the second protocol, MTP was
      inactivated prior to metabolic labeling of protein and lipid, and secretion of
      newly labeled apoB and TG as lipoproteins was monitored after oleate supplement.
      Under this condition, MTP inhibition decreased incorporation of newly labeled TG
      (by 80%) and hB48 (80%) into hB48-VLDL but did not affect their incorporation
      into hB48-HDL. Additionally, MTP inhibition decreased incorporation of newly
      labeled TG (by 50%) and rB100 (by 90%) into rB100-VLDL. Thus, normal activity of
      MTP is required for the oleate-induced secretion of hB48-VLDL from McA-RH7777
      cells.

PMID- 9139670
TI  - Structural analysis of a tumor-produced sulfated glycoprotein capable of
      initiating muscle protein degradation.
AB  - A material of Mr 24,000 has been isolated from a cachexia-inducing mouse tumor
      (MAC16) and shown to initiate protein degradation in isolated gastrocnemius
      muscle. Biological activity was destroyed by preincubation with peptide N
      glycosidase F (PNGase F) and endo-alpha-N-acetylgalactosaminidase (O-glycosidase)
      but not by neuraminidase or trypsin. Antibody reactivity was destroyed by
      treatment with periodate, indicating carbohydrate moieties to be the antigenic
      determinants. Antigenic activity was also reduced by treatment with PNGase F and
      O-glycosidase and was completely destroyed by treatment with chondroitinase ABC
      but was unaffected by treatment with either trypsin or chymotrypsin, confirming
      that the N- and O-linked sulfated oligosaccharide chains were both the antigenic
      and biological determinants. Biosynthetic labeling of MAC16 cells using a
      combination of [35S]sulfate and [6-3H]GlcN gave a single component of Mr 24,000
      containing both radiolabels. Similar material could not be isolated from a cell
      line (MAC13) originating from a tumor that does not cause cachexia in vivo.
      Digestion of 3H/35S material with PNGase F produced two fragments of Mr 14,000
      and 10,000 containing both radiolabels, and digestion with O-glycosidase produced
      three fragments of Mr 14,000, 6,000, and 4, 000, the first two contained both
      radiolabels and the third contained only 3H. Digestion of the fragment of Mr
      14,000 released by PNGase F with O-glycosidase also gave fragments of Mr 6,000
      and 4, 000. The products from both digestions were acidic as determined by anion
      exchange chromatography on DEAE-cellulose. The negative charge on the fragment of
      Mr 4,000 was removed by treatment with alkaline phosphatase. This suggests that
      the charge originated from phosphate residues, and this has been confirmed by
      biosynthetic labeling of MAC16 cells with [32P]orthophosphate, where radiolabel
      was incorporated into material of Mr 24,000 and into the fragment of Mr 4,000
      after treatment with O-glycosidase. To determine the size of the polypeptide core
      MAC16 cells were biosynthetically labeled with L-[2,5-3H]His which after chemical
      deglycosylation produced a major component of Mr 4,000. These results suggest a
      model for the Mr 24, 000 material consisting of a central polypeptide chain of Mr
      4,000 and with phosphate residues that may be attached to the polypeptide or a
      short oligosaccharide chain containing GlcN, one O-linked sulfated
      oligosaccharide chain containing GlcN, and of Mr 6,000 and one N-linked sulfated
      oligosaccharide chain of Mr 10,000 also containing GlcN. Neither chain was
      cleaved into disaccharides with chondroitinase ABC, suggesting that the material
      is a sulfated glycoprotein.

PMID- 9139671
TI  - Protein kinase C-mediated phosphorylation of HIV-I nef in human cell lines.
AB  - Stable human cell lines expressing the human immunodeficiency virus type I (HIV
      I) Nef protein from inducible promoters were used to analyze the phosphorylation
      status of Nef in vivo. Nef phosphorylation in both HeLa and Jurkat cells was
      stimulated by phorbol ester treatment. Phosphoamino acid analysis revealed a
      predominance of phosphoserine with a small proportion of phosphothreonine.
      Treatment of cells with selective protein kinase inhibitors revealed that Nef
      phosphorylation was markedly reduced by bisindolylmaleimide, an inhibitor of
      protein kinase C, but was unaffected by inhibitors of mitogen-activated protein
      kinase kinase or cAMP-dependent kinase. These data implicate protein kinase C in
      Nef phosphorylation in vivo, and thus confirm and extend earlier in vitro data.
      Phosphorylation of a nonmyristoylated Nef mutant was impaired, suggesting that
      membrane targeting of Nef was required for phosphorylation. This was expected
      given that activated protein kinase C translocates from the cytosol to the plasma
      membrane. However, analysis of the subcellular localization of phosphorylated
      wild-type Nef revealed that both the cytosolic and membrane-associated pools of
      Nef were phosphorylated to an equivalent extent. Thus the significance of
      myristoylation for Nef function may be in influencing protein conformation,
      although these data could be explained by a transient and dynamic interaction
      between myristoylated Nef and the plasma membrane.

PMID- 9139672
TI  - On the voltage dependence of the mitochondrial permeability transition pore. A
      critical appraisal.
AB  - The mitochondrial permeability transition pore, a cyclosporin A-sensitive
      channel, can be opened by the addition of protonophoric uncouplers such as
      carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) after energy-dependent
      accumulation of Ca2+. We have proposed that the relevant effect of FCCP on the
      pore is membrane depolarization, suggesting that this channel is voltage
      dependent (Bernardi, P. (1992) J. Biol. Chem. 267, 8334-8339). Here, we
      reconsider this hypothesis in the light of recent observations suggesting that
      increased production of reactive oxygen species and/or direct effects of FCCP,
      rather than membrane depolarization, could be the actual triggers of the FCCP
      dependent permeability transition. We show that although reactive oxygen species
      can contribute to the permeability transition, pore opening by FCCP can still be
      observed under strict anaerobiosis after ATP-dependent Ca2+ accumulation and that
      the permeability transition can be induced by the addition of valinomycin to
      respiring mitochondria treated with nigericin in low potassium medium. In this
      system, pore opening in increasing fractions of mitochondria depends on the
      concentration of valinomycin, i.e. on the magnitude of the potassium current that
      determines the extent of membrane depolarization. We conclude that the
      permeability transition pore is directly modulated by the membrane potential in
      intact isolated rat liver mitochondria.

PMID- 9139673
TI  - Ribosomal binding site of release factors RF1 and RF2. A new translational
      termination assay in vitro.
AB  - We have established a new in vitro assay for translational termination. It
      consists of 70 S ribosomes bound to a synthetic RNA minimessenger via interaction
      with P-site binding fMet-tRNAfMet. If the A-site codon is a stop signal, release
      activity can be measured by quantifying hydrolyzed formylmethionine.
      Characteristics of this assay in terms of reaction time, ion concentration,
      release factor RF1 and RF2 concentration, and competition with A-site-decoding
      tRNA are discussed. The new assay shows that polypeptide chain release activity
      is directly dependent on the presence of a stop codon in the ribosomal A-site.

PMID- 9139674
TI  - Metabolism of leukotriene C4 in gamma-glutamyl transpeptidase-deficient mice.
AB  - We have investigated the metabolism of leukotriene C4 (LTC4) in gamma-glutamyl
      transpeptidase (GGT)-deficient mice (Lieberman, M. W., Wiseman, A. L., Shi, Z-Z.,
      Carter, B. Z., Barrios, R., Ou, C-N., Chevez-Barrios, P., Wang, Y., Habib, G. M.,
      Goodman, J. C., Huang, S. L., Lebovitz, R. M., and Matzuk, M. M. (1996) Proc.
      Natl. Acad. Sci. U. S. A. 93, 7923-7926) and have found substantial conversion of
      LTC4 to leukotriene D4 by high performance liquid chromatography and continuous
      flow fast atom bombardment-tandem mass spectrometric analyses. LTC4-converting
      activity has a tissue distribution different from GGT with highest activity in
      spleen followed by small intestine, kidney, and pancreas and lower activity in
      liver and lung. The activity is membrane-bound and is inhibited by acivicin, a
      known inhibitor of GGT. The enzyme was partially purified from the small
      intestine of GGT-deficient mice by papain treatment and gel filtration
      chromatography. The partially purified fragment released by papain has an
      apparent molecular mass of 65-70 kDa and the same substrate specificity as the
      tissue homogenate. In addition to LTC4, S-decyl-GSH is also cleaved. GSH itself,
      oxidized GSH, and the synthetic substrates used to analyze GGT activity (gamma
      glutamyl-p-nitroanilide and gamma-glutamyl-4-methoxy-2-naphthylamide) are not
      substrates for this newly discovered enzyme. These data demonstrate that in
      addition to GGT at least one other enzyme cleaves LTC4 in mice. To reflect this
      enzyme's preferred substrate, we suggest that it be named gamma-glutamyl
      leukotrienase.

PMID- 9139675
TI  - The integrin alpha1 A-domain is a ligand binding site for collagens and laminin.
AB  - The integrin alpha1beta1 is a cell surface receptor for collagens and laminin.
      The alpha1 subunit contains an A-domain, and the A-domains of other integrins are
      known to mediate ligand binding. To determine the role of the alpha1 A-domain in
      ligand binding and the extent to which it reproduced the ligand binding activity
      and specificity of the parent molecule, we produced recombinant alpha1 A-domain
      and tested its ability to bind collagens and laminin. In solid phase assays, the
      A-domain from alpha1 was found to bind to collagen I, collagen IV, and laminin in
      a largely cation-dependent manner. The alpha2 A-domain, from the alpha2beta1
      integrin, also bound to these ligands, but the binding hierarchy differed from
      that seen for alpha1. This is the first demonstration of laminin binding by A
      domains. Specificity of A-domain-ligand binding was further investigated using
      the triple-helical proteolytic fragment of collagen IV, CB3, and its
      subfragments, F1 and F4. alpha1 A-domain bound to all three fragments, while the
      alpha2 A-domain bound CB3 less well and exhibited little binding to F1 and no
      binding to F4. These differences mirror previous reports of distinct integrin
      binding sites in collagen IV and for the first time identify a limited
      proteolytic fragment of a ligand that contains integrin A-domain binding
      activity. To gain insight into the contribution that the A-domain makes to ligand
      binding within the whole integrin heterodimer, we measured binding constants for
      A-domain-collagen interactions using surface plasmon resonance biosensor
      technology. The values obtained were similar to those reported for intact
      integrin binding, suggesting that the A-domain is the major collagen binding site
      in the alpha1beta1 and alpha2beta1 integrins.

PMID- 9139676
TI  - Cyclin-dependent kinase 5 (Cdk5) activation domain of neuronal Cdk5 activator.
      Evidence of the existence of cyclin fold in neuronal Cdk5a activator.
AB  - Neuronal Cdk5 activator (Nck5a) differs from other cyclin-dependent kinase (Cdk)
      activators in that its amino acid sequence is only marginally similar to the
      cyclin consensus sequence. Nevertheless, computer modeling has suggested that
      Nck5a contains the cyclin-fold motif recently identified in the crystal structure
      of cyclin A. In the present study, a number of truncation mutants and
      substitution mutants of the Nck5a were produced and tested for the Cdk5
      activation and Cdk5 binding activity. The active domain of Nck5a determined by
      using the truncation mutants consists of the region spanning residues 150 to 291.
      The size of Nck5a active domain is essentially the same as that of cyclin A
      required for Cdk2 activation (Lees, E. M., and Harlow, E. (1993) Mol. Cell. Biol.
      13, 1194-1201). The change, or the lack of change, in Cdk5 activation activity
      observed with a number of substitution mutants may be understood on the basis of
      structure and function relationship of cyclin A. These results provide support to
      the previous suggestion (Brown, N. R., Noble, M. E. M., Endicott, J. A., Garman,
      E. F., Wakatsuki, S., Mitchell, E., Rasmussen, B., Hunt, T., and Johnson, L. N.
      (1995) Structure 3, 1235-1247) that the activation domain of Nck5a adopts a
      conformation similar to that of cyclin A. They also provide a partial answer to
      the question of how Nck5a, a non-cyclin, activates a cyclin-dependent kinase.

PMID- 9139677
TI  - Nitric oxide prevents oxidative damage produced by tert-butyl hydroperoxide in
      erythroleukemia cells via nitrosylation of heme and non-heme iron. Electron
      paramagnetic resonance evidence.
AB  - We studied protective effects of NO against tert-butylhydroperoxide (t-BuOOH)
      induced oxidations in a subline of human erythroleukemia K562 cells with
      different intracellular hemoglobin (Hb) concentrations. t-BuOOH-induced formation
      of oxoferryl-Hb-derived free radical species in cells was demonstrated by low
      temperature EPR spectroscopy. Intensity of the signals was proportional to Hb
      concentrations and was correlated with cell viability. Peroxidation of
      phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine,
      phosphatidylinositol, and cardiolipin metabolically labeled with oxidation
      sensitive cis-parinaric acid was induced by t-BuOOH. An NO donor, (Z)-1-[N-(3
      ammoniopropyl)-N-(n-propyl)amino]-diazen-1-iu m-1, 2-diolate], produced non-heme
      iron dinitrosyl complexes and hexa- and pentacoordinated Hb-nitrosyl complexes in
      the cells. Nitrosylation of non-heme iron centers and Hb-heme protected against t
      BuOOH-induced: (a) formation of oxoferryl-Hb-derived free radical species, (b)
      peroxidation of cis-parinaric acid-labeled phospholipids, and (c) cytotoxicity.
      Since NO did not inhibit peroxidation induced by an azo-initiator of peroxyl
      radicals, 2, 2'-azobis(2,4-dimethylvaleronitrile), protective effects of NO were
      due to formation of iron-nitrosyl complexes whose redox interactions with t-BuOOH
      prevented generation of oxoferryl-Hb-derived free radical species.

PMID- 9139678
TI  - The conserved asparagine and arginine are essential for catalysis of mammalian
      adenylyl cyclase.
AB  - Mammalian adenylyl cyclases have two homologous cytoplasmic domains (C1 and C2),
      and both domains are required for the high enzymatic activity. Mutational and
      genetic analyses of type I and soluble adenylyl cyclases suggest that the C2
      domain is catalytically active and the C1 domain is not; the role of the C1
      domain is to promote the catalytic activity of the C2 domain. Two amino acid
      residues, Asn-1025 and Arg-1029 of type II adenylyl cyclase, are conserved among
      the C2 domains, but not among the C1 domains, of adenylyl cyclases with 12
      putative transmembrane helices. Mutations at each amino acid residue alone result
      in a 30-100-fold reduction in Kcat of adenylyl cyclase. However, the same
      mutations do not affect the Km for ATP, the half-maximal concentration (EC50) for
      the C2 domain of type II adenylyl cyclase to associate with the C1 domain of type
      I adenylyl cyclase and achieve maximal enzyme activity, or the EC50 for forskolin
      to maximally activate enzyme activity with or without Gsalpha. This indicates
      that the mutations at these two residues do not cause gross structural
      alteration. Thus, these two conserved amino acid residues appear to be crucial
      for catalysis, and their absence from the C1 domains may account for its lack of
      catalytic activity. Mutations at both amino acid residues together result in a
      3,000-fold reduction in Kcat of adenylyl cyclase, suggesting that these two
      residues have additive effects in catalysis. A second site suppressor of the Asn
      1025 to Ser mutant protein has been isolated. This suppressor has 17-fold higher
      activity than the mutant and has a Pro-1015 to Ser mutation.

PMID- 9139679
TI  - The kinase domain of Jak2 mediates induction of bcl-2 and delays cell death in
      hematopoietic cells.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3,
      and IL-5 stimulate DNA synthesis and proliferation and inhibit apoptosis in
      hematopoietic cells. Multiple signal pathways are activated by binding of these
      ligands to their receptors, which share a common beta subunit. Janus protein
      kinase 2 (Jak2) binds to the membrane proximal domain of the beta chain and is
      phosphorylated on receptor ligation. To explore the role of Jak2 in the
      regulation of specific signal transduction pathways, we constructed fusion
      proteins with a CD16 external domain, a CD7 transmembrane region, and a Jak2
      cytoplasmic domain. This cytoplasmic domain consisted either of wild type Jak2
      (CD16/Jak2-W) or Jak2 mutations with deletions of (a) the amino terminus
      (CD16/Jak2-N), (b) kinase-like domain (CD16/Jak2-B), (c) kinase domain (CD16/Jak2
      C), or (d) amino-terminal and kinase-like domains, leaving the kinase domain
      (CD16/Jak-K) intact. In contrast to the CD16/Jak2-W fusion protein, which
      requires cross-linking for activation, CD16/Jak2-N, CD16/Jak2-B, and CD16/Jak2-K
      were constitutively phosphorylated, and they stimulated Shc phosphorylation and
      increased binding of STAT to DNA in Ba/F3 cells. Cell lines derived from IL-3
      dependent Ba/F3 cells stably transfected with CD16/Jak2-W, CD16/Jak2-N, or
      CD16/Jak2-B mammalian expression vectors died at a rate similar to that of the
      parental cells on IL-3 deprivation. In contrast, CD16/Jak2-K cell lines exhibited
      increased expression of bcl-2 and pim-1 mRNA and maintained their viability when
      compared with control cell lines. Thus, activation of tyrosine phosphorylation by
      creating a CD16/Jak2-K fusion is sufficient to activate pathways that prevent
      cell death.

PMID- 9139680
TI  - Subunit assembly and guanine nucleotide exchange activity of eukaryotic
      initiation factor-2B expressed in Sf9 cells.
AB  - Eukaryotic initiation factor-2B (eIF-2B) is a guanine nucleotide exchange factor
      (GEF) that plays a key role in the regulation of protein synthesis. In this
      study, we have used the baculovirus-infected Sf9 insect cell system to express
      and characterize the five dissimilar subunits of rat eIF-2B. GEF activity was
      detected in extracts of Sf9 cells expressing the epsilon-subunit alone and was
      greatly increased when all five subunits were coexpressed. In addition, high GEF
      activity was observed in extracts containing a four-subunit complex lacking the
      alpha-subunit. Assembly of an eIF-2B holoprotein was confirmed by
      coimmunoprecipitation of all five subunits. Gel filtration chromatography
      revealed that recombinant eIF-2B had the same molecular mass as eIF-2B purified
      from rat liver and that it did indeed possess GEF activity. Phosphorylation of
      the substrate eIF-2 inhibited the GEF activity of the five-subunit eIF-2B; this
      inhibition required the eIF-2B alpha-subunit. The results demonstrate that eIF
      2Balpha functions as a regulatory subunit that is not required for GEF activity,
      but instead mediates the regulation of eIF-2B by substrate phosphorylation.
      Furthermore, eIF-2Bepsilon is necessary and is perhaps sufficient for GEF
      activity in vitro.

PMID- 9139681
TI  - Subunit interactions in the Na,K-ATPase explored with the yeast two-hybrid
      system.
AB  - Subunit interactions of the alpha1- and beta1-subunits of the chicken Na,K-ATPase
      were explored with the yeast two-hybrid system. Gal4-fusion proteins containing
      domains of the alpha1- and beta1-subunits were designed for examining both
      intersubunit and intrasubunit protein-protein interactions. Regions of the alpha-
      and beta-subunits known to be involved in alpha-beta-subunit assembly were
      positive in two-hybrid assay, supporting the validity of the assays. A library of
      beta-subunit ectodomains with C-terminal truncations was screened to find the
      maximal truncation retaining an interaction with the alpha-subunit extracellular
      H7H8 loop (where H7 refers to the seventh membrane span, and so on). The maximal
      truncation removed all the cysteines involved in disulfide bridges, leaving only
      63 amino acids of the beta-subunit ectodomain. Scanning alanine mutagenesis led
      to identification of an evolutionarily conserved sequence of four amino acids
      (SYGQ) in the extracellular H7H8 loop of the alpha-subunit that is crucial to
      alpha-beta-intersubunit interactions. Oligomerization studies with single domains
      failed to detect self-association of either of the two large cytosolic loops
      (H2H3 and H4H5) within the alpha-subunit. However, evidence was found for an
      interaction between these two cytoplasmic loops.

PMID- 9139682
TI  - Angiotensin II stimulates tyrosine phosphorylation and activation of insulin
      receptor substrate 1 and protein-tyrosine phosphatase 1D in vascular smooth
      muscle cells.
AB  - Angiotensin II (Ang II) and insulin-like growth factor I (IGF I) stimulate
      intracellular signaling events through binding to their respective G-protein
      coupled and growth factor receptors. In rat aortic vascular smooth muscle cells,
      IGF I (20 ng/ml) induced a sustained (>30 min) increase in the tyrosine
      phosphorylation of both Src-homology 2 domain-docking insulin receptor substrate
      1 (IRS-1) and Src-homology 2-binding tyrosine phosphatase 1D (PTP-1D). In
      addition, IGF I stimulated PTP-1D phosphatase activity. Ang II (10(-7) M) also
      increased the tyrosine phosphorylation of IRS-1 (4-fold), PTP-1D (5-fold), and
      PTP-1D activity (3-4-fold), but with a more transient time course. Ang II also
      induced PTP-1D.IRS-1 complex formation. These Ang II-induced events were not
      affected by preincubation with an anti-IGF I antibody, suggesting that Ang II's
      actions were not mediated via the autocrine secretion of IGF I. Anti-PTP-1D
      antibody electroporation attenuated Ang II-induced PTP-1D.IRS-1 complex formation
      and PTP-1D tyrosine phosphorylation and activation. Our findings show that the
      tyrosine phosphorylation of IRS-1 and PTP-1D represents a convergent
      intracellular signaling cascade stimulated by both growth factor (i.e. IGF I) and
      G-protein-coupled (i.e. AT1) receptors.

PMID- 9139683
TI  - Identification of a novel gene cluster participating in menaquinone (vitamin K2)
      biosynthesis. Cloning and sequence determination of the 2-heptaprenyl-1,4
      naphthoquinone methyltransferase gene of Bacillus stearothermophilus.
AB  - We recently described the isolation and sequence analysis of a DNA region
      containing the genes of Bacillus stearothermophilus heptaprenyl diphosphate
      synthase, which catalyzes the synthesis of the prenyl side chain of menaquinone-7
      of this bacterium. Sequence analyses revealed the presence of three open reading
      frames (ORFs), designated as ORF-1, ORF-2, and ORF-3, and the structural genes of
      the heptaprenyl diphosphate synthase were proved to consist of ORF-1 (heps-1) and
      ORF-3 (heps-2) (Koike-Takeshita, A., Koyama, T., Obata, S., and Ogura, K. (1995)
      J. Biol. Chem. 270, 18396-18400). The predicted amino acid sequence of ORF-2 (234
      amino acids) contains a methyltransferase consensus sequence and shows a 22%
      identity with UbiG of Escherichia coli, which catalyzes S-adenosyl-L-methionine
      dependent methylation of 2-octaprenyl-3-methyl-5-hydroxy-6-methoxy-1,4
      benzoquinone. These pieces of information led us to identify the ORF-2 gene
      product. The cell-free homogenate of the transformant of E. coli with an
      expression vector of ORF-2 catalyzed the incorporation of S-adenosyl-L-methionine
      into menaquinone-8, indicating that ORF-2 encodes 2-heptaprenyl-1,4
      naphthoquinone methyltransferase, which participates in the terminal step of the
      menaquinone biosynthesis. Thus it is concluded that the ORF-1, ORF-2, and ORF-3
      genes, designated heps-1, menG, and heps-2, respectively, form another cluster
      involved in menaquinone biosynthesis in addition to the cluster of menB, menC,
      menD, and menE already identified in the Bacillus subtilis and E. coli
      chromosomes.

PMID- 9139684
TI  - Mutagenesis and chemical rescue indicate residues involved in beta-aspartyl-AMP
      formation by Escherichia coli asparagine synthetase B.
AB  - Site-directed mutagenesis and kinetic studies have been employed to identify
      amino acid residues involved in aspartate binding and transition state
      stabilization during the formation of beta-aspartyl-AMP in the reaction mechanism
      of Escherichia coli asparagine synthetase B (AS-B). Three conserved amino acids
      in the segment defined by residues 317-330 appear particularly crucial for
      enzymatic activity. For example, when Arg-325 is replaced by alanine or lysine,
      the resulting mutant enzymes possess no detectable asparagine synthetase
      activity. The catalytic activity of the R325A AS-B mutant can, however, be
      restored to about 1/6 of that of wild-type AS-B by the addition of guanidinium
      HCl (GdmHCl). Detailed kinetic analysis of the rescued activity suggests that Arg
      325 is involved in stabilization of a pentacovalent intermediate leading to the
      formation beta-aspartyl-AMP. This rescue experiment is the second example in
      which the function of a critical arginine residue that has been substituted by
      mutagenesis is restored by GdmHCl. Mutation of Thr-322 and Thr-323 also produces
      enzymes with altered kinetic properties, suggesting that these threonines are
      involved in aspartate binding and/or stabilization of intermediates en route to
      beta-aspartyl-AMP. These experiments are the first to identify residues outside
      of the N-terminal glutamine amide transfer domain that have any functional role
      in asparagine synthesis.

PMID- 9139685
TI  - Differential allosteric regulation of prostaglandin H synthase 1 and 2 by
      arachidonic acid.
AB  - Prostaglandins are synthesized by prostaglandin H synthase (PGHS) 1 and 2. PGHS2
      is regulated through inducible expression. We report here the regulation of PGHS1
      activity by substrate-dependent cooperative activation. The cooperativity is
      characterized by a Hill coefficient of 1.29 +/- 0.06, a curved Eadie-Scatchard
      plot, and activation by low concentrations of competitive inhibitors. The
      activation also appears to induce a conformational change in the cyclooxygenase
      site. The cooperativity produces a 2-4-fold greater rate of PGHS2-dependent
      prostaglandin formation compared with PGHS1-dependent prostaglandin formation at
      arachidonic acid concentrations below 0.5 microM. A consequence of the PGHS1
      cooperativity is that the affinity of many cyclooxygenase inhibitors for PGHS1
      decreases in parallel to the activation by arachidonic acid. In contrast, the
      affinity of these inhibitors for PGHS2 is unaffected by the changes in
      arachidonic acid concentration. This results in a dramatic difference in
      PGHS2/PGHS1 selectivity at different arachidonic acid concentrations.

PMID- 9139686
TI  - Structural determinants for agonist binding affinity to thromboxane/prostaglandin
      endoperoxide (TP) receptors. Analysis of chimeric rat/human TP receptors.
AB  - The two most extensively characterized thromboxane/prostaglandin endoperoxide
      (TP) receptors, from human platelets and rat vascular smooth muscle, exhibit
      thromboxane agonist [15-(1alpha,2beta(5Z), 3alpha-(1E,3S), 4alpha)]-7-[3-hydroxy
      4-(p-iodophenoxy)-1-butenyl-7-oxabi cyclohepteno ic acid (I-BOP) binding
      affinities that differ by an order of magnitude, rat TP having the higher
      affinity. We utilized this difference in I-BOP affinity to identify structural
      determinants of TP receptor heterogeneity. No significant difference was found in
      the rank order of affinities for a series of thromboxane receptor ligands to bind
      to cloned human TPalpha versus rat TP, indicating that these represent species
      homologs, not distinct TP subtypes. Structural determinants for observed
      differences in I-BOP binding Kd were localized by creating chimeric human/rat TP
      followed by mutational substitution of specific critical amino acids. Initially,
      seven chimeric receptors with splice sites in transmembranes 1, 2, 4, or 7 were
      constructed and expressed in HEK293 cells for analysis of ligand binding
      properties. Substitution of any part except the carboxyl tail of the human TP
      into the rat TP resulted in a receptor with I-BOP binding affinity intermediate
      between the two. Analysis of chimeras in which only the extracellular amino
      terminus and a portion of transmembrane 1 were switched localized the determinant
      of high affinity binding to the region between amino acids 3 and 40. Using this
      chimera, amino acids in the human portion (extracellular amino terminus and part
      of transmembrane 1) were replaced with analogous amino acids from rat TP to
      regain high affinity I-BOP binding. Only when amino acid Val37 and either Val36
      or Ala40 were reverted to their respective rat TP counterparts (Ala36, Leu37, and
      Gly40, respectively) was high affinity I-BOP binding recovered. The mechanism for
      the increased I-BOP affinity may be the lengthening of the amino acid side chain
      at position 37, thus extending this group further into the putative I-BOP binding
      pocket, with compensatory shortening of side chains in spatially adjacent amino
      acids.

PMID- 9139688
TI  - Identification of glypican as a dual modulator of the biological activity of
      fibroblast growth factors.
AB  - Heparan sulfate moieties of cell-surface proteoglycans modulate the biological
      responses to fibroblast growth factors (FGFs). We have reported previously that
      cell-associated heparan sulfates inhibit the binding of the keratinocyte growth
      factor (KGF), but enhance the binding of acidic FGF to the KGF receptor, both in
      keratinocytes, which naturally express this receptor, and in rat myoblasts, which
      ectopically express it (Reich-Slotky, R., Bonneh-Barkay, D., Shaoul, E., Berman,
      B., Svahn, C. M., and Ron, D. (1994) J. Biol. Chem. 269, 32279-32285). The
      proteoglycan bearing these modulatory heparan sulfates was purified to
      homogeneity from salt extracts of rat myoblasts by anion-exchange and FGF
      affinity chromatography and was identified as rat glypican. Affinity-purified
      glypican augmented the binding of acidic FGF and basic FGF to human FGF receptor
      1 in a cell-free system. This effect was abolished following digestion of
      glypican by heparinase. Addition of purified soluble glypican effectively
      replaced heparin in supporting basic FGF-induced cellular proliferation of
      heparan sulfate-negative cells expressing recombinant FGF receptor-1. In
      keratinocytes, glypican strongly inhibited the mitogenic response to KGF while
      enhancing the response to acidic FGF. Taken together, these findings demonstrate
      that glypican plays an important role in regulating the biological activity of
      fibroblast growth factors and that, for different growth factors, glypican can
      either enhance or suppress cellular responsiveness.

PMID- 9139687
TI  - Modulation of E2F activity is linked to interferon-induced growth suppression of
      hematopoietic cells.
AB  - E2F is a heterodimeric transcription factor that controls transcription of
      several growth-regulatory genes including cdc2. To investigate the mechanism of
      interferon-alpha (IFN-alpha)-mediated growth suppression of hematopoietic cells,
      we examined the effect of IFN-alpha on the expression and function of E2F using
      IFN-sensitive Daudi cells. Down-regulation of E2F-1, a subunit of E2F, was
      observed after 8 h of culture with IFN-alpha; expression of E2F-4, another
      subunit of E2F, and DP-1, a heterodimeric partner of E2F, was unaffected. Gel
      shift assays revealed that the DNA binding activity of free E2F, which is
      composed of E2F-1 and E2F-4, was inhibited by IFN-alpha. In contrast, IFN-alpha
      did not affect the DNA binding ability of E2F-1 and E2F-4 in a complex with
      retinoblastoma (RB) susceptibility gene family proteins including pRB, p107, and
      p130. IFN-alpha could induce dephosphorylation of pRB, thereby turning active E2F
      pRB complexes into transcriptional repressors. Transient chloramphenicol
      acetyltransferase assays revealed that the activity of the E2F-dependent cdc2
      promoter was suppressed by IFN-alpha. These results suggest that the
      antiproliferative action of IFN-alpha is mediated through the modulation of E2F
      activity in two different ways: down-regulation of transcriptionally active free
      E2F and conversion of E2F-pRB complexes into transcriptional repressors.

PMID- 9139689
TI  - Activation of transcription factor NF-kappaB and p38 mitogen-activated protein
      kinase is mediated by distinct and separate stress effector pathways.
AB  - Mitogen-activated protein (MAP) kinases are important mediators of the cellular
      stress response. Here, we investigated the relationship between activation of the
      MAP kinase p38 and transcription factor NF-kappaB. Different forms of cellular
      stress were found to preferentially trigger either p38 or NF-kappaB. Arsenite or
      osmotic stress potently activated p38 but were ineffective in inducing NF-kappaB
      activation. Tumor necrosis factor-alpha and hydrogen peroxide, in contrast, led
      to NF-kappaB activation but only modestly stimulated p38. The activation of NF
      kappaB was strongly abolished by antioxidants, while the activity of p38 and
      transcription factor AP-1 were increased. Inhibition of small GTPases including
      Rac and Cdc42 prevented p38 and AP-1 activation without interfering with NF
      kappaB. In addition, inhibition of p38 by a pharmacological inhibitor or a
      dominant-negative mutant of MAP kinase kinase-6, an activator of the p38 pathway,
      interfered with NF-kappaB-dependent gene expression but not its DNA binding
      activity. Our results indicate that activation of p38 and NF-kappaB are mediated
      by separate pathways, which may converge further downstream in the cell nucleus.
      Different forms of cellular stress, however, initially trigger distinct signaling
      cascades involving either oxidative stress or GTPase-coupled pathways.

PMID- 9139691
TI  - Arachidonic acid drives mini-glucagon action in cardiac cells.
AB  - Recent studies have shown that glucagon is processed by cardiac cells into its
      COOH-terminal (19-29) fragment, mini-glucagon, and that this metabolite is an
      essential component of the contractile positive inotropic effect of glucagon
      (Sauvadet, A., Rohn, T., Pecker, F. and Pavoine, C. (1996) Circ. Res. 78, 102
      109). We now show that mini-glucagon triggers arachidonic acid (AA) release from
      [3H]AA-loaded embryonic chick ventricular myocytes via the activation of a
      phospholipase A2 sensitive to submicromolar Ca2+ concentrations. The
      phospholipase A2 inhibitor, AACOCF3, prevented mini-glucagon-induced [45Ca2+]
      accumulation into the sarcoplasmic reticulum, but inhibitors of lipoxygenase,
      cyclooxygenase, or epoxygenase pathways were ineffective. AA applied exogenously,
      at 0. 3 microM, reproduced the effects of mini-glucagon on Ca2+ homeostasis and
      contraction. Thus AA: (i) caused [45Ca2+] accumulation into a sarcoplasmic
      reticulum compartment sensitive to caffeine; 2) potentiated caffeine-induced Ca2+
      mobilization from cells loaded with Fura-2; 3) acted synergistically with
      glucagon or cAMP to increase both the amplitude of Ca2+ transients and
      contraction of electrically stimulated cells. AA action was dose-dependent and
      specific since it was mimicked by its non-hydrolyzable analog 5,8,11,14
      eicosatetraynoic acid but not reproduced by other lipids such as, arachidic acid,
      linolenic acid, cis-5,8,11,14,17-eicosapentaenoic acid, cis-4,7,10,13,16, 19
      docosahexaenoic acid, or arachidonyl-CoA, even in the micromolar range. We
      conclude that AA drives mini-glucagon action in the heart and that the positive
      inotropic effect of glucagon on heart contraction relies on both second
      messengers, cAMP and AA.

PMID- 9139690
TI  - Identification of framework residues in a secreted recombinant antibody fragment
      that control production level and localization in Escherichia coli.
AB  - The monoclonal antibody 5T4, directed against a human tumor-associated antigen,
      was expressed as a secreted Fab superantigen fusion protein in Escherichia coli.
      The product is a putative agent for immunotherapy of non-small cell lung cancer.
      During fermentation, most of the fusion protein leaked out from the periplasm to
      the growth medium at a level of approximately 40 mg/liter. This level was notably
      low compared with similar products containing identical CH1, CL, and superantigen
      moieties, and the Fv framework was therefore engineered. Using hybrid molecules,
      the light chain was found to limit high expression levels. Substituting five
      residues in VL increased the level almost 15 times, exceeding 500 mg/liter in the
      growth medium. Here, the substitutions Phe-10 --> Ser, Thr-45 --> Lys, Thr-77 -->
      Ser, and Leu-78 --> Val were most powerful. In addition, replacing four VH
      residues diminished cell lysis during fermentation. Thereby the product was
      preferentially located in the periplasm instead of the growth medium, and the
      total yield was more than 700 mg/liter. All engineered products retained a high
      affinity for the tumor-associated antigen. It is suggested that at least some of
      the identified framework residues generally have to be replaced to obtain high
      level production of recombinant Fab products in E. coli.

PMID- 9139692
TI  - Gene 4 DNA primase of bacteriophage T7 mediates the annealing and extension of
      ribo-oligonucleotides at primase recognition sites.
AB  - The 63-kDa gene 4 primase of bacteriophage T7 recognizes a core trinucleotide
      sequence, 5'-GTC-3', on single-stranded DNA at which it catalyzes the synthesis
      of the ribodinucleotide pppAC. The dinucleotide is extended to a tetranucleotide
      primer at the sites 5'-(G/T)GGTC-3' and 5'-GTGTC-3'. In the presence of T7
      primase, T7 DNA polymerase extends the synthetic ribotetranucleotide pACCA (1
      microM), but not pCACA, on M13 DNA templates. The reaction is specific for T7 DNA
      polymerase and depends on dTTP and translocation of the gene 4 protein. T7
      primase extends the dinucleotide AC and trinucleotide ACC to ACCC in the presence
      of CTP and an appropriate template, whereas other dinucleotides are extended less
      efficiently; the deoxyribodinucleotide dAC is not extended. The Cys4 zinc motif
      of the primase is essential for extension of the dinucleotides. The 5'-cryptic
      cytidine of the recognition sequence is essential for extension of the
      dinucleotide AC to tri- and tetranucleotides. At a preformed replication fork,
      the dinucleotide AC provides for primer synthesis on the lagging strand. The
      synthesis of all Okazaki fragments is initiated by primers arising from the
      recognition sequence 5'-GGGTC-3'; none arise at an adjacent 5'-GGGTT-3' sequence.
      If ADP or AMP replaces ATP in the primase reaction, primers terminating in di- or
      monophosphate, respectively, are synthesized.

PMID- 9139693
TI  - Angiotensin II-induced down-regulation of inositol trisphosphate receptors in WB
      rat liver epithelial cells. Evidence for involvement of the proteasome pathway.
AB  - Chronic stimulation of WB rat liver epithelial cells by angiotensin II (Ang II)
      resulted in the down-regulation of both type I and type III myo-inositol 1,4,5
      trisphosphate receptors (IP3Rs). Stimulation with vasopressin, bradykinin,
      epidermal growth factor, or 12-O-tetradecanoylphorbol-13-acetate was without
      effect. Ang II-induced down-regulation of IP3Rs could be detected within 2 h and
      resulted in an inhibition of IP3-induced Ca2+ release from permeabilized cells.
      IP3R down-regulation was reversible, and both homo- and heterooligomers of IP3Rs
      were equally susceptible to Ang II-induced degradation. Chloroquine and NH4Cl
      increased the basal levels of IP3Rs by 2-fold, suggesting that the basal turnover
      of IP3Rs occurs via a lysosomal pathway. However, Ang II-induced degradation of
      IP3R was not affected by these inhibitors, suggesting that stimulated degradation
      of IP3Rs occurs via a non-lysosomal pathway. The cysteine protease and
      proteasomal inhibitor N-acetyl-Leu-Leu-norleucinal completely prevented Ang II
      mediated down-regulation of IP3Rs, whereas the structural analog N-acetyl-Leu-Leu
      methioninal was without effect. Lactacystin, a highly specific proteasome
      inhibitor, also blocked Ang II-mediated IP3R degradation. Stimulation with Ang II
      increased the amount of IP3R immunoprecipitated by anti-ubiquitin antibodies. We
      conclude that Ang II-stimulated IP3R degradation involves enhanced ubiquitination
      of the protein and degradation by the proteasome pathway.

PMID- 9139694
TI  - Cloning of cutinase transcription factor 1, a transactivating protein containing
      Cys6Zn2 binuclear cluster DNA-binding motif.
AB  - Hydroxy fatty acids from plant cutin were shown previously to induce the
      expression of the cutinase gene via a palindromic sequence located at -159 base
      pairs of the cutinase gene in Fusarium solani f. sp. pisi (Nectria hematococca
      mating type VI). Of the two overlapping palindromes in this sequence, palindrome
      2 was found to be essential for the inducibility of cutinase by hydroxy fatty
      acids. Screening of a phage expression library with the concatenated palindrome 2
      as probe detected a distinct cDNA clone encoding a polypeptide designated
      cutinase transcription factor 1alpha (CTF1alpha) with a calculated molecular
      weight of 101,109. This protein contains a Cys6Zn2 binuclear cluster motif
      sharing homology to the Cys6Zn2 binuclear cluster DNA-binding domains of
      transcription factors from Saccharomyces cerevisiae, S. carlsbergensis,
      Kluyveromyces lactis, Neurospora crassa, Aspergillus nidulans, and A. flavus.
      CTF1alpha, expressed in Escherichia coli, showed specific binding to the
      palindrome 2 DNA fragment but not to palindrome 1 or mutant palindrome 2 DNA
      fragments, suggesting specific binding of CTF1alpha to palindrome 2. When
      CTF1alpha was expressed as a fusion protein with the nuclear localization
      sequence of SV40 in yeast, it transactivated the native cutinase promoter fused
      to the chloramphenicol acetyl transferase (cat) gene. Mutation of palindrome 2
      but not palindrome 1 abolished this transactivation. Thus, CTF1alpha positively
      acts in vivo by binding selectively to palindrome 2 of the cutinase gene
      promoter.

PMID- 9139695
TI  - Chaperonin-mediated folding of green fluorescent protein.
AB  - Chaperonin-mediated folding of green fluorescent protein (GFP) was examined by
      real-time monitoring of recovery of fluorescence and by gel filtration high
      performance liquid chromatography. Acid-denatured GFP can fold spontaneously upon
      dilution into the neutral buffer. When Escherichia coli GroEL/ES was present,
      folding of GFP was arrested. Folding was resumed by subsequent addition of 100
      microM or 1 mM ATP, and native GFP was regenerated to 100% yield. When folding
      was resumed by 10 microM ATP (1.4 mol/mol GroEL subunit), about 60% of GFP
      recovered native structure, and one-half of them (30%) was found to be still
      bound to GroEL/ES, indicating the occurrence of folding in the central cavity of
      the GroEL ring underneath GroES (cis-folding). Because the overall rates of
      GroEL/ES-, ATP-mediated GFP folding were all similar to that of spontaneous
      folding, it was concluded that cis-folding proceeded as fast as spontaneous
      folding. The GroEL/ES-bound native GFP was observed only when both GroES and ATP
      (but not ADP) were present in the folding mixture. Holo-chaperonin from Thermus
      thermophilus, which was purified as a cpn60/10 complex, exhibited the similar cis
      folding. Consistently, ATP-dependent exchange of cpn10 in the holo-chaperonin
      with free cpn10 was observed.

PMID- 9139697
TI  - Proteins with glycosylphosphatidylinositol (GPI) signal sequences have divergent
      fates during a GPI deficiency. GPIs are essential for nuclear division in
      Trypanosoma cruzi.
AB  - Glycosylphosphatidylinositols (GPIs) are membrane anchors for cell surface
      proteins of several major protozoan parasites of humans, including Trypanosoma
      cruzi, the causative agent of Chagas' disease. To investigate the general role of
      GPIs in T. cruzi, we generated GPI-deficient parasites by heterologous expression
      of T. brucei GPI-phospholipase C. Putative protein-GPI intermediates were
      depleted, causing the biochemical equivalent of a dominant-negative loss of
      function mutation in the GPI pathway. Cell surface expression of major GPI
      anchored proteins was diminished in GPI-deficient T. cruzi. Four proteins that
      are normally GPI-anchored in T. cruzi exhibited different fates during the GPI
      shortage; Ssp-4 and p75 were secreted prematurely, while protease gp50/55 and p60
      were degraded intracellularly. These observations demonstrate that secretion and
      intracellular degradation of GPI-anchored proteins may occur in the same genetic
      background during a GPI deficiency. We postulate that the interaction between a
      protein-GPI transamidase and the COOH-terminal GPI signal sequence plays a
      pivotal role in determining the fate of these proteins. At a nonpermissive GPI
      deficiency, T. cruzi amastigotes inside mammalian cells replicated their single
      kinetoplast but failed at mitosis. Hence, in these protozoans, GPIs appear to be
      essential for nuclear division, but not for mitochondrial duplication.

PMID- 9139696
TI  - Cloning and functional characterization of the ornithokinin receptor. Recognition
      of the major kinin receptor antagonist, HOE140, as a full agonist.
AB  - Kinins are proinflammatory peptides that dilate vessels, increase vascular
      permeability, contract smooth muscles, and provoke pain. The known mammalian
      kinin receptors are classified as two subtypes, i.e. the B1 receptor triggered by
      [des-Arg9]bradykinin and inhibited by [des-Arg9,Leu8]bradykinin, and the B2
      receptor stimulated by bradykinin and antagonized by HOE140. Here we report the
      cloning of a non-mammalian kinin receptor gene amplified from genomic chicken
      DNA. The protein predicted from the open reading frame shows 31 and 49% sequence
      identity to the human B1 and B2 receptors, respectively, suggesting that it
      represents a G protein-coupled receptor of the kinin receptor family. The
      recombinantly expressed chicken receptor had IC50 values of 4.7 nM for the
      authentic ligand, ornithokinin ([Thr6,Leu8]bradykinin), 3.8 nM for HOE140, and
      >/=10 microM for bradykinin, [des-Arg9]bradykinin, and [des-Arg9,Leu8]bradykinin.
      Ornithokinin and HOE140 at nanomolar concentrations stimulated intracellular
      inositol phosphate accumulation and induced a significant transient rise in
      intracelluar free Ca2+, whereas bradykinin was ineffective even at 100 nM. Hence
      the principal B2 receptor antagonist HOE140 is a potent agonist of the chicken
      kinin receptor. This unique pharmacological profile classifies the ornithokinin
      receptor as a novel subtype among kinin receptors and will facilitate further
      molecular studies on ligand binding and receptor activation.

PMID- 9139698
TI  - Interaction of the DF3/MUC1 breast carcinoma-associated antigen and beta-catenin
      in cell adhesion.
AB  - The DF3/MUC1 mucin-like glycoprotein is aberrantly overexpressed in human breast
      carcinomas. The functional role of DF3 is unknown. The present studies
      demonstrate that DF3 associates with beta-catenin. Similar findings have been
      obtained for gamma-catenin but not alpha-catenin. DF3, like E-cadherin and the
      adenomatous polyposis coli gene product, contains an SXXXXXSSL site that is
      responsible for direct binding to beta-catenin. The results further demonstrate
      that interaction of DF3 and beta-catenin is dependent on cell adhesion. These
      findings and the role of beta-catenin in cell signaling support a role for DF3 in
      the adhesion of epithelial cells.

PMID- 9139699
TI  - Cloning and characterization of a novel murine beta chemokine receptor, D6.
      Comparison to three other related macrophage inflammatory protein-1alpha
      receptors, CCR-1, CCR-3, and CCR-5.
AB  - The beta-chemokine macrophage inflammatory protein-1alpha (MIP-1alpha) is
      chemotactic for many hemopoietic cell types and can inhibit hemopoietic stem cell
      (HSC) proliferation, effects mediated through G-protein coupled heptahelical
      receptors. We have isolated cDNAs for seven chemokine receptors, CCR-1 to -5, MIP
      1alphaRL1, and a novel cDNA, D6. Chinese hamster ovary cells expressing CCR-1, 
      3, -5, and D6 bound 125I-murine MIP-1alpha: the order of affinity was D6 > CCR-5
      > CCR-1 > CCR-3. Each bound a distinct subset of other beta-chemokines: the order
      of competition for 125I-murine MIP-1alpha on D6 was murine MIP-1alpha > human and
      murine MIP-1beta > human RANTES approximately JE > human MCP-3 > human MCP-1.
      Human MIP-1alpha and the alpha-chemokines did not compete. Like other chemokine
      receptors, D6 induced transient increases in [Ca2+] in HEK 293 cells upon ligand
      binding. D6 mRNA was abundant in lung and detectable in many other tissues. Bone
      marrow cell fractionation demonstrated T-cell and macrophage/monocyte expression
      of D6, and CCR-1, -3, and -5. Moreover, we could detect expression of CCR-3, CCR
      5, and to a greater extent D6 in a cell population enriched for HSCs. Thus, we
      have characterized four murine beta chemokine receptors that are likely involved
      in mediating the pro-inflammatory functions of MIP-1alpha and other chemokines,
      and we present D6, CCR-3, and CCR-5 as candidate receptors in MIP-1alpha-induced
      HSC inhibition.

PMID- 9139700
TI  - Molecular cloning and expression of amadoriase isoenzyme (fructosyl amine:oxygen
      oxidoreductase, EC 1.5.3) from Aspergillus fumigatus.
AB  - Amadoriase is an enzyme catalyzing the oxidative deglycation of Amadori products
      to yield corresponding amino acids, glucosone, and H2O2. We previously reported
      the purification and characterization of two amadoriase isozymes from Aspergillus
      sp. that degrade both glycated low molecular weight amines and amino acids
      (Takahashi, M., Pischetsrieder, M., and Monnier, V. M. (1997) J. Biol. Chem. 272,
      3437-3443). To identify the primary structure of the enzymes, we have prepared a
      cDNA library from Aspergillus fumigatus induced with fructosyl propylamine and
      isolated a clone using polyclonal anti-amadoriase II antibody. The primary
      structure of the enzyme deduced from the nucleotide sequence comprises 438 amino
      acid residues with a predicted molecular mass of 48,798 Da. The deduced primary
      structure exhibits the presence of an ADP-binding motif near the NH2 terminus.
      The identity of the amadoriase II cDNA was further confirmed by expression in
      Escherichia coli cells with an inducible expression system. Northern blotting
      analysis revealed that amadoriase II was induced by fructosyl propylamine in a
      dose-dependent manner.

PMID- 9139701
TI  - Antisense RNA control of plasmid R1 replication. The dominant product of the
      antisense rna-mrna binding is not a full RNA duplex.
AB  - The replication frequency of plasmid R1 is controlled by an antisense RNA (CopA)
      that binds to its target site (CopT) in the leader region of repA mRNA and
      inhibits the synthesis of the replication initiator protein RepA. Previous
      studies on CopA-CopT pairing in vitro revealed the existence of a primary loop
      loop interaction (kissing complex) that is subsequently converted to an almost
      irreversible duplex. However, the structure of more stable binding intermediates
      that lead to the formation of a complete duplex was speculative. Here, we
      investigated the interaction between CopA and CopT by using Pb(II)-induced
      cleavages. The kissing complex was studied using a truncated antisense RNA (CopI)
      that is unable to form a full duplex with CopT. Furthermore, RNase III, which is
      known to process the CopA-CopT complex in vivo, was used to detect the existence
      of a full duplex. Our data indicate that the formation of a full CopA-CopT duplex
      appears to be a very slow process in vitro. Unexpectedly, we found that the loop
      loop interaction persists in the predominant CopA-CopT complex and is stabilized
      by intermolecular base pairing involving the 5'-proximal 30 nucleotides of CopA
      and the complementary region of CopT. This almost irreversible complex suffices
      to inhibit ribosome binding at the tap ribosome binding site and may be the
      inhibitory complex in vivo.

PMID- 9139702
TI  - Development of an isotope dilution assay for precise determination of insulin, C
      peptide, and proinsulin levels in non-diabetic and type II diabetic individuals
      with comparison to immunoassay.
AB  - We describe the application of a stable isotope dilution assay (IDA) to determine
      precise insulin, C-peptide, and proinsulin levels in blood by extraction from
      serum and quantitation by mass spectrometry using analogues of each target
      protein labeled with stable isotopes. Insulin and C-peptide levels were also
      determined by immunoassay, which gave consistently higher results than by IDA,
      the relative difference being larger at low concentrations. Insulin, C-peptide,
      and proinsulin levels were all shown by IDA to be higher in type II diabetics
      than in non-diabetics, with mean values rising from 22 (+/- 2) to 92 (+/- 8), 335
      (+/- 11) to 821 (+/- 24), and 6 (+/- 1) to 37 (+/- 3) pM, respectively.
      Interestingly, the ratio between IDA and immunoassay values for insulin levels
      increased from 1.3 in non-diabetics to 1.7 in type II diabetics. The ratio
      between proinsulin and insulin levels by IDA increased from 0.24 in non-diabetics
      to 0.36 in type II diabetics, whereas the ratio between C-peptide and insulin
      levels by IDA decreased from 17.6 to 10.7. This disproportionate change in
      protein levels between different types of individuals has implications for the
      metabolism of insulin in the diabetics studied (type II) and suggests that C
      peptide levels are not always a reliable guide as to pancreatic insulin
      secretion. In addition, levels of the 33-residue C-peptide (partially trimmed
      form) were shown to be less than 10% that of the fully trimmed 31-residue C
      peptide levels, and we tested IDA in a clinical context by two post-pancreatic
      graft studies. IDA was shown to give direct, positive identification of the
      target protein with unrivaled accuracy, avoiding many of the problems associated
      with present methodology for protein determination.

PMID- 9139703
TI  - Kinetics of CO ligation with nitric-oxide synthase by flash photolysis and
      stopped-flow spectrophotometry.
AB  - Interaction of CO with hemeproteins has physiological importance. This is
      especially true for nitric-oxide synthases (NOS), heme/flavoenzymes that produce
      .NO and citrulline from L-arginine (Arg) and are inhibited by CO in vitro. The
      kinetics of CO ligation with both neuronal NOS and its heme domain module were
      determined in the presence and absence of tetrahydrobiopterin and Arg to allow
      comparison with other hemeproteins. Geminate recombination in the nanosecond time
      domain is followed by bimolecular association in the millisecond time domain.
      Complex association kinetics imply considerable heterogeneity but can be
      approximated with two forms, one fast (2-3 x 10(6) M-1 s-1) and another slow (2-4
      x 10(4) M-1 s-1). The relative proportions of the two forms vary with conditions.
      For the heme domain, fast forms dominate except in the presence of both
      tetrahydrobiopterin and Arg. In the holoenzyme, slow forms dominate except when
      both reagents are absent. Geminate recombination is substantial, approximately
      50%, only when fast forms predominate. Stopped-flow mixing found dissociation
      constants near 0.3 s-1. These data imply an equilibrium constant such that very
      little CO should bind at physiological conditions unless large CO concentrations
      are present locally.

PMID- 9139704
TI  - Post-translational modifications of alpha5beta1 integrin by glycosaminoglycan
      chains. The alpha5beta1 integrin is a facultative proteoglycan.
AB  - Cell-fibronectin interactions, mediated through several different receptors, have
      been implicated in a wide variety of cellular properties. Among the cell surface
      receptors for fibronectin, integrins are the best characterized, particularly the
      prototype alpha5beta1 integrin. Using [125I]iodine cell surface labeling or
      metabolic radiolabeling with sodium [35S]sulfate, we identified alpha5beta1
      integrin as the only sulfated integrin among beta1 integrin heterodimers
      expressed by the human melanoma cell line Mel-85. This facultative sulfation was
      confirmed not only by immunoprecipitation reactions using specific monoclonal
      antibodies but also by fibronectin affinity chromatography, two-dimensional
      electrophoresis, and chemical reduction. The covalent nature of alpha5beta1
      integrin sulfation was evidenced by its resistance to treatments with high ionic,
      chaotrophic, and denaturing agents such as 4 M NaCl, 4 M MgCl2, 8 M urea, and 6 M
      guanidine HCl. Based on deglycosylation procedures as chemical beta-elimination,
      proteinase K digestion, and susceptibility to glycosaminoglycan lyases
      (chondroitinase ABC and heparitinases I and II), it was demonstrated that the
      alpha5beta1 heterodimer and alpha5 and beta1 integrin subunits were
      proteoglycans. The importance of alpha5beta1 sulfation was strengthened by the
      finding that this molecule is also sulfated in MG-63 (human osteosarcoma) and HCT
      8 (human colon adenocarcinoma) cells.

PMID- 9139705
TI  - Ornithine decarboxylase expression leads to translocation and activation of
      protein kinase CK2 in vivo.
AB  - Ornithine decarboxylase (ODC) is the key initial enzyme in the biosynthesis of
      polyamines. Since polyamines have been shown to enhance protein kinase CK2
      activity in vitro, ODC was overexpressed to examine the role of polyamines in CK2
      regulation in vivo. Infection of Balb/MK cells with an ODC retrovirus to elevate
      ODC and polyamine levels increased overall protein phosphorylation as well as CK2
      protein levels and enzyme activity in mimosine- or nocodazole- arrested cells.
      Immunofluorescence microscopy and enzyme analyses of subcellular fractions from
      ODC-overexpressing cells demonstrated translocation of CK2 from the cytoplasm to
      the nucleus with no apparent loss of cytoplasmic CK2 activity, suggesting
      polyamine activation of the remaining cytoplasmic enzyme. Similarly, K6/ODC
      transgenic mice exhibited higher ODC and CK2 enzyme activities than their normal
      littermates. ODC-immunostained cells in the transgenic skin also stained
      intensely for CK2 protein. Primary cultures of K6/ODC keratinocytes also
      exhibited increased ODC and CK2 enzyme activities compared with those from normal
      littermates. However, the addition of difluoromethylornithine, a specific ODC
      inhibitor, to the transgenic keratinocytes reduced both intracellular polyamine
      levels and CK2 enzyme activity. These results suggest that polyamines regulate
      the CK2 enzyme by affecting its cellular distribution as well as its enzyme
      activity and levels.

PMID- 9139706
TI  - Cloning and characterization of a cDNA encoding a protein synthesis initiation
      factor-2alpha (eIF-2alpha) kinase from Drosophila melanogaster. Homology To yeast
      GCN2 protein kinase.
AB  - Phosphorylation of the alpha subunit of the eukaryotic initiation factor 2 (eIF
      2alpha) is one of the best-characterized mechanisms for downregulating protein
      synthesis in mammalian cells in response to various stress conditions. In
      Drosophila, such a regulatory mechanism has not been elucidated. We report the
      molecular cloning and characterization of DGCN2, a Drosophila eIF-2alpha kinase
      related to yeast GCN2 protein kinase. DGCN2 contains all of the 12 catalytic
      subdomains characteristic of eukaryotic Ser/Thr protein kinases and the conserved
      sequence of eIF-2alpha kinases in subdomain V. A large insert of 94 amino acids,
      which is characteristic of eIF-2alpha kinases, is also present between subdomains
      IV and V. It is particularly notable that DGCN2 possesses an amino acid sequence
      related to class II aminoacyl-tRNA synthetases, a unique feature of yeast GCN2
      protein kinase. DGCN2 expression is developmentally regulated. During
      embryogenesis, DGCN2 mRNA is dynamically expressed in several tissues.
      Interestingly, at later stages this expression becomes restricted to a few cells
      of the central nervous system. Affinity-purified antibodies, raised against a
      synthetic peptide based on the predicted DGCN2 sequence, specifically
      immunoprecipitated an eIF-2alpha kinase activity and recognized an approximately
      175 kDa phosphoprotein in Western blots of Drosophila embryo extracts.

PMID- 9139708
TI  - Mice with genetic gamma-glutamyl transpeptidase deficiency exhibit
      glutathionuria, severe growth failure, reduced life spans, and infertility.
AB  - A mouse mutant with glutathionuria was discovered by screening for amino
      acidurias in the progeny of ethylnitrosourea-mutagenized mice. Total glutathione
      concentration was increased in both blood and urine but decreased in liver
      homogenates from affected mice. Glutathionuric mice exhibited lethargy, severe
      growth failure, shortened life spans and infertility. gamma-Glutamyl
      transpeptidase activity was deficient in kidney homogenates of glutathionuric
      mice. The glutathionuric phenotype in these mice is inherited as an autosomal
      recessive trait. This mouse mutant will be a useful animal model for the study of
      gamma-glutamyl transpeptidase physiology and glutathione metabolism.

PMID- 9139707
TI  - Molecular cloning, expression, and functional significance of a cytochrome P450
      highly expressed in rat heart myocytes.
AB  - A cDNA encoding a P450 monooxygenase was amplified from reverse transcribed rat
      heart and liver total RNA by polymerase chain reaction using primers based on the
      5'- and 3'-end sequences of two rat pseudogenes, CYP2J3P1 and CYP2J3P2. Sequence
      analysis revealed that this 1,778-base pair cDNA contained an open reading frame
      and encoded a new 502 amino acid protein designated CYP2J3. Based on the deduced
      amino acid sequence, CYP2J3 was approximately 70% homologous to both human CYP2J2
      and rabbit CYP2J1. Recombinant CYP2J3 protein was co-expressed with NADPH
      cytochrome P450 oxidoreductase in Sf9 insect cells using a baculovirus expression
      system. Microsomal fractions of CYP2J3/NADPH-cytochrome P450 oxidoreductase
      transfected cells metabolized arachidonic acid to 14,15-, 11,12-, and 8, 9
      epoxyeicosatrienoic acids and 19-hydroxyeicosatetraenoic acid as the principal
      reaction products (catalytic turnover, 0.2 nmol of product/nmol of cytochrome
      P450/min at 37 degrees C). Immunoblotting of microsomal fractions prepared from
      rat tissues using a polyclonal antibody raised against recombinant CYP2J2 that
      cross-reacted with CYP2J3 but not with other known rat P450s demonstrated
      abundant expression of CYP2J3 protein in heart and liver. Immunohistochemical
      staining of formalin-fixed paraffin-embedded rat heart tissue sections using the
      anti-CYP2J2 IgG and avidin-biotin-peroxidase detection localized expression of
      CYP2J3 primarily to atrial and ventricular myocytes. In an isolated-perfused rat
      heart model, 20 min of global ischemia followed by 40 min of reflow resulted in
      recovery of only 44 +/- 6% of base-line contractile function. The addition of 5
      microM 11, 12-epoxyeicosatrienoic acid to the perfusate prior to global ischemia
      resulted in a significant 1.6-fold improvement in recovery of cardiac
      contractility (69 +/- 5% of base line, p = 0.01 versus vehicle alone).
      Importantly, neither 14,15-epoxyeicosatrienoic acid nor 19
      hydroxyeicosatetraenoic acid significantly improved functional recovery following
      global ischemia, demonstrating the specificity of the biological effect for the
      11, 12-epoxyeicosatrienoic acid regioisomer. Based on these data, we conclude
      that (a) CYP2J3 is one of the predominant enzymes responsible for the oxidation
      of endogenous arachidonic acid pools in rat heart myocytes and (b) 11,12
      epoxyeicosatrienoic acid may play an important functional role in the response of
      the heart to ischemia.

PMID- 9139709
TI  - Heme oxygenase-2 is a hemoprotein and binds heme through heme regulatory motifs
      that are not involved in heme catalysis.
AB  - The heme oxygenase (HO) system degrades heme to biliverdin and CO and releases
      chelated iron. In the primary sequence of the constitutive form, HO-2, there are
      three potential heme binding sites: two heme regulatory motifs (HRMs) with the
      absolutely conserved Cys-Pro pair, and a conserved 24-residue heme catalytic
      pocket with a histidine residue, His151 in rat HO-2. The visible and pyridine
      hemochromogen spectra suggest that the Escherichia coli expressed purified HO-2
      is a hemoprotein. The absorption spectrum, heme fluorescence quenching, and heme
      titration analysis of the wild-type protein versus those of purified double
      cysteine mutant (Cys264/Cys281 --> Ala/Ala) suggest a role of the HRMs in heme
      binding. While the His151 --> Ala mutation inactivates HO-2, Cys264 --> Ala and
      Cys281 --> Ala mutations individually or together (HO-2 mut) do not decrease HO
      activity. Also, Pro265 --> Ala or Pro282 --> Ala mutation does not alter HO-2
      activity. Northern blot analysis of ptk cells indicates that HO-2 mRNA is not
      regulated by heme. The findings, together with other salient features of HO-2 and
      the ability of heme-protein complexes to generate oxygen radicals, are consistent
      with HO-2, like five other HRM-containing proteins, having a regulatory function
      in the cell.

PMID- 9139711
TI  - Early expression of a novel nucleotide receptor in the neural plate of Xenopus
      embryos.
AB  - Extracellular ATP functions as a neurotransmitter and neuromodulator in the adult
      nervous system, and a signaling molecule in non-neural tissue, acting either via
      ligand-gated ion channels (P2X) or G-protein-coupled receptors (P2Y). ATP can
      cause an increase in intracellular Ca2+ (Ca2+i) in embryonic cells and so
      regulate cell proliferation, migration, and differentiation. We have isolated a
      Xenopus cDNA encoding a novel P2Y receptor, XlP2Y, which is expressed abundantly
      in developing embryos. Recombinant XlP2Y responds equally to all five naturally
      occurring nucleoside triphosphates (ATP, UTP, CTP, GTP, and ITP), which elicit a
      biphasic Ca2+-dependent Cl- current (ICl,Ca) where the second phase persists for
      up to 60 min. XlP2Y also causes a continuous release of Ca2+i and a low level
      persistent activation of ICl,Ca in Xenopus oocytes through the spontaneous efflux
      of ATP. mRNAs for XlP2Y are expressed transiently in the neural plate and tailbud
      during Xenopus development, coincident with neurogenesis. This restricted pattern
      of expression and novel pharmacological features confer unique properties to
      XlP2Y, which may play a key role in the early development of neural tissue.

PMID- 9139710
TI  - Molecular cloning and expression of a chloride ion channel of cell nuclei.
AB  - Ion channels are known to be present on the plasma membrane of virtually all
      cells and have been found on the membranes of various intracellular organelles.
      However, until recently they were believed not to occur at the nuclear membrane.
      In this study we describe the molecular cloning and characterization of a nuclear
      ion channel protein, designated nuclear chloride channel-27 (NCC27), from the
      human myelomonocytic cell line, U937. NCC27 is a novel chloride ion channel
      protein that was found to localize principally to the cell nucleus. Its only
      known homologue is a bovine chloride ion channel protein (p64) believed to
      localize to internal organelles. NCC27 therefore represents the first human
      member of a new class of organellar chloride ion channel proteins.

PMID- 9139712
TI  - Evidence for a role of the gut hormone PYY in the regulation of intestinal fatty
      acid-binding protein transcripts in differentiated subpopulations of intestinal
      epithelial cell hybrids.
AB  - Peptide tyrosine tyrosine (PYY) is a gut hormone present in endocrine cells in
      the lower intestine that can be released by the presence of luminal free fatty
      acids (FFAs). The biological action of this peptide includes inhibition of gut
      motility and gastrointestinal and pancreatic secretions. Intestinal fatty acid
      binding protein (I-FABP) binds FFA and may be involved in their cytosolic
      trafficking. Quantitative in situ hybridization on heterogeneous populations of
      small intestinal somatic cell hybrids selected for endogenous I-FABP expression
      (hBRIE 380i cells) demonstrated a 5-fold increase in I-FABP transcripts in
      response to PYY (within 6 h) that was confined to clusters of differentiated
      cells, whereas ribonuclease protection assays performed on heterogeneous
      populations of these cells showed no significant differences. High affinity PYY
      receptors, with an IC50 of 5-50 pM, were identified in both differentiated and
      nondifferentiated cell populations, as determined by competitive binding assays
      and autoradiography. In situ hybridization of rat ileal tissue also revealed
      differing patterns of mRNA expression for liver fatty acid-binding protein (L
      FABP) and I-FABP. Only I-FABP mRNA was detected in the villus tips. This
      localization correlated with the expression pattern of I-FABP mRNA in the hBRIE
      380i cells where changes in transcripts were observed only in differentiated
      cells that did not incorporate bromodeoxyuridine. The sustained expression of I
      FABP transcripts in the villar tips suggests (unlike L-FABP) that older
      terminally differentiated cell populations of the mucosa can still be PYY
      responsive. These studies demonstrate that physiological concentrations of PYY
      can regulate I-FABP and place this peptide in a key position as part of a
      feedback system that determines the processing of cytosolic FFA in the
      enterocyte. In addition, these studies suggest a mechanism whereby luminal agents
      can modulate expression of proteins in terminally differentiated cells in the
      gastrointestinal mucosa.

PMID- 9139713
TI  - Controlling amyloid beta-peptide fibril formation with protease-stable ligands.
AB  - We have previously shown that short peptides incorporating the sequence KLVFF can
      bind to the approximately 40amino acid residue Alzheimer amyloid beta-peptide
      (Abeta) and disrupt amyloid fibril formation (Tjernberg, L. O., Naslund, J.,
      Lindqvist, F., Johansson, J., Karlstrom, A. R., Thyberg, J., Terenius, L., and
      Nordstedt, C. (1996) J. Biol. Chem. 271, 8545-8548). Here, it is shown that KLVFF
      binds stereospecifically to the homologous sequence in Abeta (i.e. Abeta16-20).
      Molecular modeling suggests that association of the two homologous sequences
      leads to the formation of an atypical anti-parallel beta-sheet structure
      stabilized primarily by interaction between the Lys, Leu, and COOH-terminal Phe.
      By screening combinatorial pentapeptide libraries exclusively composed of D-amino
      acids, several ligands with a general motif containing phenylalanine in the
      second position and leucine in the third position were identified. Ligands
      composed of D-amino acids were not only capable of binding Abeta but also
      prevented formation of amyloid-like fibrils. These ligands are protease-resistant
      and may thus be useful as experimental agents against amyloid fibril formation in
      vivo.

PMID- 9139714
TI  - Identification of inheritance modes of mitochondrial diseases by introduction of
      pure nuclei from mtDNA-less HeLa cells to patient-derived fibroblasts.
AB  - A nuclear genome delivery system was developed to deduce the modes of inheritance
      of the clinical phenotypes observed in patients with mitochondrial diseases by
      transfer of pure nuclei from normal cells to fibroblasts from the patients. The
      problem of possible contamination of the nuclei with a small amount of mtDNA was
      overcome by using mtDNA-less (rho0) human cells as nuclear donors. In this study,
      intercellular transfer of pure nuclei was carried out by simple fusion of rho0
      HeLa cells with 533 fibroblasts from a patient with a fatal mitochondrial
      disease, which were deficient in cytochrome c oxidase and succinate dehydrogenase
      activities. The results showed that the cytochrome c oxidase and succinate
      dehydrogenase activities were restored by the introduction of pure HeLa nuclei,
      suggesting that the observed phenotypes of mitochondrial dysfunction were not due
      to mtDNA mutations but to nuclear, recessive mutations. Thus, our nuclear
      transfer system is effective for determining whether a mitochondrial or nuclear
      genome of a patient is responsible for a disease and whether deficiency of
      mitochondrial enzymes, including enzymes exclusively encoded by nuclear genomes,
      is transmitted in a nuclear recessive or nuclear dominant way, providing the
      parents of the patients with valuable information for genetic counseling on the
      risk of mitochondrial diseases in their next babies.

PMID- 9139715
TI  - Arrest in primitive erythroid cell development caused by promoter-specific
      disruption of the GATA-1 gene.
AB  - To elucidate the in vivo function of GATA-1 during hematopoiesis, we specifically
      disrupted the erythroid promoter of the GATA-1 gene in embryonic stem cells and
      generated germ line chimeras. Male offspring of chimeras bearing the targeted
      mutation were found to die by 12.5 days post coitus due to severe anemia while
      heterozygous females displayed characteristics ranging from severe anemia to
      normal erythropoiesis. When female heterozygotes were crossed with transgenic
      males carrying a reporter gene, which specifically marks primitive erythroid
      progenitors, massive accumulation of undifferentiated erythroid cells were
      observed in the yolk sacs of the GATA-1-mutant embryos, demonstrating that GATA-1
      is required for the terminal differentiation of primitive erythroid cells in
      vivo.

PMID- 9139716
TI  - Functional expression of the murine Golgi CMP-sialic acid transporter in
      saccharomyces cerevisiae.
AB  - We have functionally expressed the murine Golgi putative CMP-sialic acid
      transporter in Saccharomyces cerevisiae. Using a galactose-inducible expression
      system, S. cerevisiae vesicles were able to transport CMP-sialic acid. Transport
      was dependent on galactose induction and was temperature-dependent and saturable
      with an apparent Km of 2.9 microM. Transport was inhibited by CMP, and upon
      vesicle disruption with Triton X-100 parameters were very similar to the
      previously described CMP-sialic acid transport characteristics observed with
      mammalian Golgi vesicles. CMP-sialic acid transport induction was specific as no
      transport of UDP-galactose was observed even though the latter putative
      transporter has a high degree of amino acid sequence identity with the CMP-sialic
      acid transporter. Together, the above results demonstrate that the previously
      described cDNA encoding the putative CMP-sialic acid transporter encodes the
      transporter protein per se and suggests that this heterologous expression system
      may be used for further structural and functional studies of other Golgi membrane
      transporter proteins.

PMID- 9139717
TI  - An alternative gonadotropin-releasing hormone (GnRH) RNA splicing product found
      in cultured GnRH neurons and mouse hypothalamus.
AB  - Gonadotropin-releasing hormone (GnRH) is encoded by the proGnRH gene which
      contains four exons and three introns. In this study, two immortalized GnRH
      expressing cell lines (Gn11 and NLT) were characterized. The NLT and Gn11 cells,
      derived from a same brain tumor in a transgenic mouse, display neuronal
      morphology and neuron-specific markers. However, NLT cells secrete much higher
      levels of GnRH than Gn11 cells. To delineate the mechanism underlying this
      difference, reverse transcriptase-polymerase chain reaction and RNase protection
      assays were performed to examine proGnRH gene expression. While the mature
      proGnRH mRNA was predominately expressed in NLT cells, Gn11 cells express an
      abundant short transcript. Sequence analysis revealed that this short transcript
      contains exons 1, 3, and 4, but not exon 2, which encodes the GnRH decapeptide.
      RNase protection assays demonstrated that NLT cells express much higher levels of
      mature proGnRH mRNA than Gn11 cells. The lower level of GnRH secreting capacity
      in Gn11 cells is due, in part, to decreased expression of mature proGnRH mRNA.
      When proGnRH gene expression in the mouse brain was examined, the same short
      splicing variant was observed in the olfactory area and preoptic area-anterior
      hypothalamus. But the prevalent transcript in these regions was the mature
      proGnRH mRNA. In contrast, only the mature proGnRH mRNA was found in the caudal
      hypothalamus. These results suggest that alternative splicing may be one of the
      mechanisms regulating proGnRH gene expression in the animal brain.

PMID- 9139718
TI  - Activation of phosphatidylinositol 3-kinase by interleukin-13. An inhibitory
      signal for inducible nitric-oxide synthase expression in epithelial cell line HT
      29.
AB  - The human colonic epithelial cell line HT-29 can be induced by a combination of
      the cytokines interleukin (IL)-1alpha, tumor necrosis factor alpha, and
      interferon-gamma to express the inducible form of nitric-oxide synthase (iNOS;
      Kolios, G., Brown, Z., Robson, R., Robertson, D. A. F., & Westwick, J. (1995) Br.
      J. Pharmacol. 116, 2866-2872). IL-13 is a potent inhibitor of cytokine-induced
      iNOS mRNA expression and nitric oxide generation in HT-29 cells via an unknown
      mechanism. We report here that in HT-29 cells, IL-13 induces a concentration and
      time-dependent increase in the formation of the lipid products of
      phosphatidylinositol (PtdIns) 3-kinase, namely phosphatidylinositol (3,4)
      bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate. IL-13 also induces a
      parallel concentration and time-dependent increase in the in vitro lipid kinase
      activity present in immunoprecipitates of the p85 regulatory subunit of PtdIns 3
      kinase. In addition, we also demonstrate that IL-13 stimulates the tyrosine
      phosphorylation of the adaptor molecule insulin receptor substrate 1, which may
      facilitate receptor coupling to PtdIns 3-kinase. Both the increases in D-3
      phosphatidylinositol lipids and the increased in vitro lipid kinase activity of
      p85 immunoprecipitates were inhibited by wortmannin and LY294002. Inhibition of
      the PtdIns 3-kinase activity was paralleled by a reversal of the ability of IL-13
      to inhibit iNOS mRNA expression and nitrite generation in HT-29 cells. These data
      demonstrate that the activation of PtdIns 3-kinase by IL-13 is a key signal that
      is responsible for the inhibition of iNOS transcription in activated epithelial
      cells.

PMID- 9139719
TI  - Mapping of amino acid residues in the p34 subunit of human single-stranded DNA
      binding protein phosphorylated by DNA-dependent protein kinase and Cdc2 kinase in
      vitro.
AB  - Human single-stranded DNA-binding protein (HSSB, also called RPA), is a
      heterotrimeric complex that consists of three subunits, p70, p34, and p11. HSSB
      is essential for the in vitro replication of SV40 DNA and nucleotide excision
      repair. It also has important functions in other DNA transactions, including DNA
      recombination, transcription, and double-stranded DNA break repair. The p34
      subunit of HSSB is phosphorylated in a cell cycle-dependent manner. Both Cdc2
      kinase and the DNA-dependent protein kinase (DNA-PK) phosphorylate HSSB-p34 in
      vitro. In this study, we show that efficient phosphorylation of HSSB-p34 by DNA
      PK requires Ku as well as DNA. The DNA-PK phosphorylation sites in HSSB-p34 have
      been mapped at Thr-21 and Ser-33. Kinetic studies demonstrated that a phosphate
      residue is first incorporated at Thr-21 followed by the incorporation of a second
      phosphate residue at Ser-33. We also identified Ser-29 as the major Cdc2 kinase
      phosphorylation site in the p34 subunit.

PMID- 9139721
TI  - Cyclin G2 is up-regulated during growth inhibition and B cell antigen receptor
      mediated cell cycle arrest.
AB  - Human cyclin G2 together with its closest homolog cyclin G1 defines a novel
      family of cyclins (Horne, M. C., Goolsby, G. L., Donaldson, K. L., Tran, D.,
      Neubauer, M., and Wahl, A. F. (1996) J. Biol. Chem. 271, 6050-6061). Cyclin G2 is
      highly expressed in the immune system where immunologic tolerance subjects self
      reactive lymphocytes to negative selection and clonal deletion via apoptosis.
      Here we investigated the effect of growth inhibitory signals on cyclin G2 mRNA
      abundance in different maturation stage-specific murine B cell lines. Upon
      treatment of wild-type and p53 null B cell lines with the negative growth factor,
      transforming growth factor beta1, or the growth inhibitory corticosteroid
      dexamethasone, cyclin G2 mRNA levels were increased in a time-dependent manner 5
      14-fold over control cell levels. Unstimulated immature B cell lines (WEHI-231
      and CH31) and unstimulated or IgM B cell receptor (BCR) -stimulated mature B cell
      lines (BAL-17 and CH12) rapidly proliferate and express low levels of cyclin G2
      mRNA. In contrast, BCR-stimulated immature B cell lines undergo growth arrest and
      coincidentally exhibit an approximately 10-fold increase in cyclin G2 transcripts
      and a decrease in cyclin D2 message. Costimulation of WEHI-231 and CH31 cells
      with calcium ionophores and protein kinase C agonists partially mimics anti-IgM
      stimulation and elicits a strong up-regulation of cyclin G2 mRNA and down
      regulation of cyclin D2 mRNA. Signaling mutants of WEHI-231 that are deficient in
      the phosphoinositide signaling pathway and consequently resistant to the BCR
      stimulus-induced growth arrest did not display a significant increase in cyclin
      G2 or decrease in cyclin D2 mRNAs when challenged with anti-IgM antibodies. The
      two polyclonal activators lipopolysaccharide and soluble gp39, which inhibit the
      growth arrest response of immature B cells, suppressed cyclin G2 mRNA expression
      induced by BCR stimulation. These results suggest that in murine B cells
      responding to growth inhibitory stimuli cyclin G2 may be a key negative regulator
      of cell cycle progression.

PMID- 9139720
TI  - SWI/SNF stimulates the formation of disparate activator-nucleosome complexes but
      is partially redundant with cooperative binding.
AB  - To investigate the potential mechanisms by which the SWI/SNF complex
      differentially regulates different genes we have tested whether transcription
      factors with diverse DNA binding domains were able to exploit nucleosome
      disruption by SWI/SNF. In addition to GAL4-VP16, the SWI/SNF complex stimulated
      nucleosome binding by the Zn2+ fingers of Sp1, the basic helix-loop-helix domain
      of USF, and the rel domain of NF-kappaB. In each case SWI/SNF action resulted in
      the formation of a stable factor-nucleosome complex that persisted after
      detachment of SWI/SNF from the nucleosome. Thus, stimulation of factor binding by
      SWI/SNF appears to be universal. The degree of SWI/SNF stimulation of nucleosome
      binding by a factor appears to be inversely related to the extent that binding is
      inhibited by the histone octamer. Cooperative binding of 5 GAL4-VP16 dimers to a
      5-site nucleosome enhanced GAL4 binding relative to a single-site nucleosome, but
      this also reduced the degree of stimulation by SWI/SNF. The SWI/SNF complex
      increased the affinity of 5 GAL4-VP16 dimers for nucleosomes equal to that of DNA
      but no further. Similarly, multimerized NF-kappaB sites enhanced nucleosome
      binding by NF-kappaB and reduced the stimulatory effect of SWI/SNF. Thus,
      cooperative binding of factors to nucleosomes is partially redundant with the
      function of the SWI/SNF complex.

PMID- 9139722
TI  - Proteinase specificity and functional diversity in point mutants of plasminogen
      activator inhibitor 1.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is a unique member of the serpin
      superfamily. The alternative behavior of PAI-1 as an inhibitor, a non-inhibitory
      substrate, or a non-reactive latent form has been shown to be dependent on the
      initial conformation. In this study, we have evaluated the effect of a
      substitution outside the reactive site loop (P18) or in the reactive site loop
      (P6 and P10) on proteinase specificity and conformational transitions in PAI-1.
      Wild-type PAI-1 (wtPAI-1) revealed the same conformational distribution pattern
      toward tissue-type plasminogen activator (t-PA) as toward urokinase-type
      plasminogen activator (u-PA) (i.e. 53 +/- 6. 9% active, 36 +/- 6.8% latent, and
      12 +/- 1.9% substrate). Inactivation of wtPAI-1 resulted in the conversion of the
      labile active form into the latent form while the stable substrate form remained
      unchanged. PAI-1-P6 (Val --> Pro at P6) revealed a target specificity for t-PA
      (39 +/- 7% versus 3 +/- 2% of the theoretical maximal value toward t-PA and u-PA,
      respectively), PAI-1-P10 (Ser --> Pro at P10) was 4-fold more active toward u-PA
      than toward t-PA, and PAI-1-P18 (Asn --> Pro at P18) exhibited inhibitory
      properties exclusively toward u-PA (41 +/- 10%). Surprisingly, inactivation of
      these mutants revealed functional and conformational transitions distinct from
      those observed for wtPAI-1. Inactivation of PAI-1-P6(Val --> Pro) resulted in a
      total conversion of the active form into the latent form and in a partial
      conversion of the substrate form into the latent form. The active forms of both
      PAI-1-P10(Ser --> Pro) and PAI-1-P18(Asn --> Pro) are also labile but, in
      contrast to the active form of wtPAI-1, convert into substrate forms. Based on
      the existence of various conformations of PAI-1, we propose an alternative
      reaction scheme describing the putative interactions between serpins and their
      target proteinases. The unusual conformational and functional flexibility of PAI
      1 that, according to the current study, appears not to be restricted to the
      reactive site loop further underlines the importance of potential structural
      rearrangements (e.g. upon binding to cofactors) in PAI-1 (or serpins in general)
      for its functional behavior at particular biological sites.

PMID- 9139723
TI  - Kalirin, a cytosolic protein with spectrin-like and GDP/GTP exchange factor-like
      domains that interacts with peptidylglycine alpha-amidating monooxygenase, an
      integral membrane peptide-processing enzyme.
AB  - Although the integral membrane proteins that catalyze steps in the biosynthesis
      of neuroendocrine peptides are known to contain routing information in their
      cytosolic domains, the proteins recognizing this routing information are not
      known. Using the yeast two-hybrid system, we previously identified P-CIP10 as a
      protein interacting with the cytosolic routing determinants of peptidylglycine
      alpha-amidating monooxygenase (PAM). P-CIP10 is a 217-kDa cytosolic protein with
      nine spectrin-like repeats and adjacent Dbl homology and pleckstrin homology
      domains typical of GDP/GTP exchange factors. In the adult rat, expression of P
      CIP10 is most prevalent in the brain. Corticotrope tumor cells stably expressing
      P-CIP10 and PAM produce longer and more highly branched neuritic processes than
      nontransfected cells or cells expressing only PAM. The turnover of newly
      synthesized PAM is accelerated in cells co-expressing P-CIP10. P-CIP10 binds to
      selected members of the Rho subfamily of small GTP binding proteins (Rac1, but
      not RhoA or Cdc42). P-CIP10 (kalirin), a member of the Dbl family of proteins,
      may serve as part of a signal transduction system linking the catalytic domains
      of PAM in the lumen of the secretory pathway to cytosolic factors regulating the
      cytoskeleton and signal transduction pathways.

PMID- 9139724
TI  - Immunoglobulin-like domain 4-mediated receptor-receptor interactions contribute
      to platelet-derived growth factor-induced receptor dimerization.
AB  - Platelet-derived growth factor (PDGF) is a dimeric growth factor that activates
      its tyrosine kinase receptor by inducing receptor dimerization. In this study, we
      investigated if receptor-receptor interactions, in addition to ligand-receptor
      interactions, contribute to the ligand-induced dimerization of the PDGF
      receptors. Analysis of two deletion mutants of the PDGF alpha-receptor indicated
      a role for Ig-like domain 4 in ligand-receptor or receptor-receptor interactions.
      When the fourth Ig-like domain of the PDGF alpha-receptor instead was replaced
      with the corresponding sequence of the stem cell factor receptor, the binding of
      PDGF-AA and -BB was not affected, nor was the ability to form homodimeric
      receptor complexes. This indicates that Ig-like domain 4 does not participate in
      ligand-receptor interactions. However, the chimeras did not form heterodimers
      with wild-type PDGF alpha- or beta-receptors. Together, these findings suggest
      that Ig-like domain 4 mediates specific receptor-receptor interactions. This
      notion was also supported by the finding that a soluble form of Ig-like domain 4
      of the PDGF alpha-receptor acted as a PDGF alpha-receptor antagonist. We conclude
      that specific receptor-receptor interactions contribute to PDGF receptor
      dimerization in vivo and that complementary epitopes in Ig-like domain 4 mediate
      these interactions. Our experiments also identify Ig-like domain 4 as a target
      for PDGF antagonists.

PMID- 9139725
TI  - The yeast Saccharomyces cerevisiae as a genetic system for obtaining variants of
      poliovirus protease 2A.
AB  - The inducible expression of poliovirus protease 2A (2Apro) blocks the growth of
      Saccharomyces cerevisiae. A number of yeast colonies that grow after 2Apro
      induction have been isolated. The majority of these clones express 2Apro to
      control levels, suggesting that their ability to divide is not due to the loss of
      2Apro gene inducibility. The sequences of the 2Apro genes isolated from 22 clones
      were determined. Most of the 2Apro sequences from these colonies contain point
      mutations in the poliovirus protease. The different variant protease sequences
      were transferred to an infectious poliovirus cDNA clone. Translation of genomic
      RNA obtained from these poliovirus mutants in cell-free systems revealed that
      some of them had defects in their ability to cleave P1-2A in cis. In addition,
      several of these variants cleaved the translation initiation factor eIF-4G
      inefficiently. Transfection of the RNA generated from the full-length poliovirus
      genomes mutated in 2Apro yielded five viable polioviruses with a small plaque
      phenotype. These five polioviruses efficiently cleaved p220 but showed defects in
      viral protein synthesis, transactivation of a leader-luciferase mRNA, and 3CD
      cleavage to 3C' and 3D'. All 2Apro mutant sequences, including those that did not
      yield viable viruses, were cloned in pTM1 vector under a T7 promoter. Only the
      2Apro variants that have activity to cleave 3CD produced viable poliovirus. Our
      findings indicate that S. cerevisiae represents a useful system for obtaining
      poliovirus 2Apro variants that may provide further insight into the role of this
      protease during the poliovirus replication cycle.

PMID- 9139726
TI  - Cloning and characterization of the promoter region of a gene encoding a 67-kDa
      glycoprotein.
AB  - A rat genomic library constructed in lambda-EMBL3 (SP6/T7) vector () was screened
      using 32P-labeled rat p67 cDNA. A clone containing a segment of 5'-upstream
      region of p67 genomic DNA was obtained. The DNA (about 1.7 kilobase pairs) was
      isolated and characterized. Sequence analysis of this DNA fragment showed that
      the 898 base pairs at the 5'-end of the upstream region was identical to several
      long interspersed nucleotide sequences. One hundred forty-eight base pairs at the
      3'-end contained the beginning of the first exon including the ATG initiator
      codon. The remaining 652 base pairs in between contained two AT-rich regions and
      several regulatory sequences. The mRNA initiation site was identified at 89 base
      pairs upstream from the translation start codon. The DNA fragment was also
      analyzed by transient transfection. When linked to a firefly luciferase reporter
      gene, this fragment enhanced transcription in a rat hepatoma cell line (KRC-7).
      Using a series of deletions in the DNA, the minimum essential promoter region
      (from -177 to -60) was identified. The promoter activity was also enhanced by
      treatment with phorbol 13-myristate 12-acetate (PMA). This enhancement required
      an AP-1 sequence (-298 to -292; 5'-TGACTCA-3') and a similar sequence (-97 to 
      88; 5'-ATGACATCAT-3'). Deletion of either of these sequences significantly
      reduced PMA enhancement. Deletion of both of these sequences almost completely
      eliminated PMA enhancement.

PMID- 9139727
TI  - p67 transcription regulates translation in serum-starved and mitogen-activated
      KRC-7 cells.
AB  - The regulation of protein synthesis was studied in KRC-7 cells (rat hepatoma)
      grown in complete medium, during serum starvation, and mitogen activation. Upon
      serum starvation, the cells lost almost completely p67 mRNA, p67 protein, and
      protein synthesis activity. After phorbol 12-myristate 13-acetate addition, the
      same serum-starved cells regained p67 mRNA, p67 protein, and protein synthesis
      activity. Also, the extracts from the serum-starved cells phosphorylated the
      eukaryotic initiation factor-2 (eIF-2) alpha-subunit. This eIF-2 alpha-subunit
      phosphorylation was not observed when the extracts from either the cells grown in
      complete medium or mitogen-activated cells were used (Gupta, S., Wu, S.,
      Chatterjee, N., Ilan, J., Ilan, J., Osterman, J. C., and Gupta, N. K. (1995) Gene
      Expr. 5, 113-122). We now report the following. 1) The eIF-2 kinase activity was
      the same in the cells grown in complete medium, after serum starvation, and
      subsequent mitogen stimulation. However, the eIF-2 kinase in the cells grown in
      complete medium and also after mitogen activation of the serum-starved cells
      cannot phosphorylate eIF-2 alpha-subunit as these cells contain p67. After
      removal of endogenous p67 by p67 antibodies, the extracts from all these cells
      similarly phosphorylated exogenously added eIF-2. 2) None of the cell extracts
      showed p67 deglycosylase activity. 3) The p67 mRNA was synthesized in serum
      starved cells by expression of a p67 cDNA. The appearance of p67 mRNA in the
      serum-starved cells was accompanied by the appearance of p67 protein. Also, the
      rates of protein synthesis in the serum-starved cells were restored nearly to the
      level observed in the confluent cells. The expression of p67 cDNA also
      significantly increased protein synthesis rates in the cells grown in complete
      medium and in mitogen-activated cells. These results show that the loss of
      protein synthesis activity in serum-starved cells was due to loss of p67 mRNA.
      The expressed p67 mRNA was stable in serum-starved cells. These results,
      therefore, suggest that the loss of p67 mRNA in serum-starved cells is due to
      loss of p67 transcription. The p67 transcription regulates translation.

PMID- 9139728
TI  - Regulation of dioxin receptor function by omeprazole.
AB  - The intracellular dioxin (aryl hydrocarbon) receptor mediates signal transduction
      by dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) and related environmental
      pollutants and functions as a ligand-activated transcription factor. In this
      study we have examined the effects on dioxin receptor function of a potentially
      novel ligand, omeprazole, which is widely clinically used as a gastric anti-ulcer
      drug. In primary human hepatocytes omeprazole potently induced cytochrome P4501A1
      mRNA expression, whereas this effect was not detected in mouse primary
      hepatocytes. In human hepatoma cells omeprazole was found to induce transcription
      of reporter genes via the xenobiotic response element that is recognized by the
      ligand-activated dioxin receptor. In contrast, the human dioxin receptor was not
      activated by omeprazole upon expression in a receptor-deficient mouse hepatoma
      cell line. In a reconstituted yeast (Saccharomyces cerevisiae) model system,
      however, both the mouse and human dioxin receptors were potently activated by
      omeprazole. Although omeprazole failed to displace dioxin in in vitro ligand
      binding assays, a residue within the ligand binding domain that is critical for
      dioxin binding in vitro was also critical for omeprazole responsiveness in vivo.
      Consistent with this observation, both omeprazole and dioxin responsiveness of
      the dioxin receptor was inhibited in mutant yeast cells expressing low levels of
      the molecular chaperone hsp90 that is critical for ligand binding activity. The
      sulfoxide group that is essential for formation of a planar conversion product of
      omeprazole was found to be critical for dioxin receptor activation. Taken
      together, these data suggest that omeprazole represents a precursor for a novel
      class of dioxin receptor agonists that are bona fide dioxin receptor ligands but
      generated in a strictly species-specific manner.

PMID- 9139729
TI  - AM67, a secretory component of the guinea pig sperm acrosomal matrix, is related
      to mouse sperm protein sp56 and the complement component 4-binding proteins.
AB  - The guinea pig sperm acrosomal matrix is the dense core of the acrosome and is
      likely to be important in acrosome biogenesis and fertilization. Isolated
      acrosomal matrices are composed of a limited number of major bands when analyzed
      by SDS-polyacrylamide gel electrophoresis, among which is a Mr 67,000 protein
      that we have termed AM67. Indirect immunofluorescence demonstrated that AM67 is
      localized to the apical segment of the cauda epididymal sperm acrosome.
      Immunoelectron microscopy further refined the localization of AM67 to the M1
      (dorsal bulge) domain within the acrosome. Using a polymerase chain reaction
      product based upon tryptic peptide sequences from AM67, a lambdagt11 guinea pig
      testis cDNA library was screened to yield two cDNA clones that encode the AM67
      peptides. Northern analysis revealed that AM67 is transcribed as a 1. 9-kilobase
      testis-specific mRNA. The complete AM67 sequence encodes a prepropolypeptide of
      533 amino acids with a calculated Mr of 59, 768. Following cleavage of a probable
      signal sequence, the polypeptide was predicted to have a Mr of 56,851 and seven
      consensus sites for asparagine-linked glycosylation. The deduced amino acid
      sequence of AM67 is most similar to those of the mouse sperm protein sp56 and the
      alpha-subunits of complement component 4-binding proteins from various mammalian
      species. Although mouse sp56 has been reported to be a cell-surface receptor for
      the murine zona pellucida glycoprotein ZP3, standard immunoelectron microscopy
      using the anti-sp56 monoclonal antibody 7C5 detected sp56 within the mouse sperm
      acrosome, but failed to detect sp56 on the surface of acrosome-intact mouse
      sperm. Furthermore, acrosomal labeling was detected in mouse sperm prepared for
      immunofluorescence using paraformaldehyde fixation, but was not observed with
      live unfixed sperm. Thus, the finding that sp56 is present within the acrosome
      provides further support that sp56 and AM67 are orthologues and suggests that
      sp56 may function in acrosomal matrix-zona pellucida interactions during and
      immediately following the acrosome reaction in the mouse.

PMID- 9139730
TI  - Cloning, expression, and catalytic mechanism of murine lysophospholipase I.
AB  - A lysophospholipase (LysoPLA I) has been purified and characterized from the
      mouse macrophage-like P388D1 cell line (Zhang, Y. Y, and Dennis, E. A. (1988) J.
      Biol. Chem. 263, 9965-9972). This enzyme has now been sequenced, cloned, and
      expressed in Escherichia coli cells. The enzyme contains 230 amino acid residues
      with a calculated molecular mass of 24.7 kDa. It has a high helical content in
      its predicated secondary structure, which is also indicated in its CD spectrum.
      The cloned LysoPLA I was purified to homogeneity from the transformed E. coli
      cells by a gel filtration column and an ion exchange column. The specific
      activity of the purified protein is 1. 47 micromol/min.mg toward 1-palmitoyl-sn
      glycero-3-phosphorylcholine at pH 8.0 and 40 degrees C, corresponding to the
      reported value of 1.3-1.7 micromol/min.mg for the protein purified from the
      P388D1 cells. In addition, the cloned protein cross-reacted with an antibody
      raised against LysoPLA I also purified from the P388D1 cells. The deduced LysoPLA
      I sequence contains a well conserved GXSXG motif found in the active site of many
      serine enzymes, and the activity of the LysoPLA I was irreversibly inhibited by
      the classical serine protease inhibitor diisopropyl fluorophosphate. Furthermore,
      site-directed mutagenesis was employed to change Ser-119 in the GXSXG motif to an
      Ala. The resulting mutant protein lost all of its lysophospholipase activity,
      even though it had the same overall protein conformation as that of the wild-type
      LysoPLA I. Therefore, LysoPLA I has been demonstrated to be a serine enzyme with
      Ser-119 at the active site.

PMID- 9139731
TI  - Expression of small extracellular chondroitin/dermatan sulfate proteoglycans is
      differentially regulated in human endothelial cells.
AB  - We have examined the expression of the small extracellular chondroitin/dermatan
      sulfate proteoglycans (CS/DS PGs), biglycan, decorin, and PG-100, which is the
      proteoglycan form of colony stimulating factor-1, in the human endothelial cell
      line EA.hy 926. We have also examined whether modulation of the phenotype of
      EA.hy 926 cells by tumor necrosis factor-alpha (TNF-alpha) is associated with
      specific changes in the synthesis of these PGs. We demonstrate that EA.hy 926
      cells, when they form monolayer cultures typical of macrovascular endothelial
      cells, express and synthesize detectable amounts of biglycan and PG-100, but not
      decorin. On SDS-polyacrylamide gel electrophoresis both PGs behave like proteins
      of the relative molecular weight of approximately 250,000. TNF-alpha that changed
      the morphology of the cells from a polygonal shape into a spindle shape and that
      also stimulated the detachment of the cells from culture dish, markedly decreased
      the net synthesis of biglycan, whereas the net synthesis of PG-100 was increased.
      These changes were parallel with those observed at the mRNA level of the
      corresponding PGs. The proportions of the different sulfated CS/DS disaccharide
      units of PGs were not affected by TNF-alpha. Several other growth
      factors/cytokines, such as interferon-gamma, fibroblast growth factors-2 (FGF-2)
      and -7 (FGF-7), interleukin-1beta, and transforming growth factor-beta, unlike
      TNF-alpha, modulated neither the morphology nor the biglycan expression of EA.hy
      926 cells under the conditions used in the experiments. However, PG-100
      expression was increased also in response to FGF-2 and -7 and transforming growth
      factor-beta. None of the above cytokines, including TNF-alpha, was able to induce
      decorin expression in the cells. Our results indicate that the regulatory
      elements controlling the expression of the small extracellular CS/DS PGs in human
      endothelial cells are different.

PMID- 9139732
TI  - Differential phosphorylation of the retinoblastoma protein by G1/S cyclin
      dependent kinases.
AB  - The retinoblastoma tumor suppressor protein, pRB, is inactivated by
      phosphorylation. While existing evidence is strong that such phosphorylation is
      mediated by one or more cyclin-dependent kinases (CDKs) active during G1/S, it
      remains unclear which of the various CDKs is responsible. We show here that three
      candidate pRB-inactivating kinases, CDK4-cyclin D1, CDK2-cyclin E, and CDK2
      cyclin A, phosphorylate pRB differentially, each on a subset of authentic pRB
      phosphorylation sites. Notably, two neighboring pRB phosphate acceptors,
      threonine 821 and threonine 826, which have previously been implicated in the
      regulation of LXCXE protein binding, are phosphorylated by different CDKs. We
      demonstrate that phosphorylation by either CDK2-cyclin A, which phosphorylates
      T821, or CDK4-cyclin D1, which phosphorylates threonine 826, can disable pRB for
      subsequent binding of an LXCXE protein. However, only one of these two kinases,
      CDK2-cyclin A, can dissociate a pre-existing LXCXE protein-pRB complex. We
      provide evidence that prior binding of an LXCXE protein blocks access to certain
      residues specifically targeted by CDK4-cyclin D1, explaining the inability of
      this kinase to resolve such complexes. While these results are not direct proof
      of the relevance of differential pRB phosphorylation in cells, our findings
      support a model whereby full phosphorylation of pRB may require the action of
      more than one kinase and explains how such differential phosphorylation by
      different CDKs might translate into a differential regulation of downstream
      effector pathways.

PMID- 9139733
TI  - Regulated binding of the protein kinase C substrate GAP-43 to the V0/C2 region of
      protein kinase C-delta.
AB  - The interaction between protein kinase C-delta and its neuronal substrate, GAP
      43, was studied. Two forms of protein kinase C-delta were isolated from COS cells
      and characterized by differences in gel mobility, GAP-43 binding, and specific
      GAP-43 and histone kinase activities. A slow migrating, low specific activity
      form of protein kinase C-delta bound directly to immobilized GAP-43. Binding was
      abolished in the presence of EGTA, suggesting Ca2+ dependence of the interaction.
      The free catalytic domain of protein kinase C-delta did not bind GAP-43,
      suggesting the existence of a binding site in the regulatory domain. Glutathione
      S-transferase-protein kinase C-delta regulatory domain fusion proteins were
      generated and tested for binding to GAP-43. The V0/C2-like amino-terminal domain
      was defined as the GAP-43-binding site. GAP-43 binding to this region is
      inhibited by EGTA and regulated at Ca2+ levels between 10(-7) and 10(-6) M. The
      interaction between protein kinase C-delta and GAP-43 was studied in intact cells
      by coexpression of the two proteins in human embryonic kidney cells followed by
      immunoprecipitation. Complex formation occurred only after treatment of the cells
      with the Ca2+ ionophore ionomycin, indicating that elevation of intracellular
      Ca2+ is required for interaction in vivo. It is concluded that protein kinase C
      delta interacts with GAP-43 through the V0/C2-like domain, outside the catalytic
      site, and that this interaction is modulated by intracellular Ca2+.

PMID- 9139734
TI  - Reconstitution of interactions between protein-tyrosine phosphatase CD45 and
      tyrosine-protein kinase p56(lck) in nonlymphoid cells.
AB  - To further understand the functional interactions between CD45 and p56(lck) in T
      cells, we stably reconstituted their expression in a nonlymphoid system. The
      results of our analyses demonstrated that CD45 could dephosphorylate tyrosine 505
      of p56(lck) in NIH 3T3 fibroblasts. As is the case for T-cells, removal of the
      unique domain of p56(lck) interfered with dephosphorylation of tyrosine 505 in
      fibroblasts, further stressing the importance of this region in the interactions
      between CD45 and p56(lck). The ability of CD45 to dephosphorylate tyrosine 505 in
      NIH 3T3 cells was also greatly influenced by the catalytic activity of p56(lck).
      Indeed, whereas CD45 provoked dephosphorylation of kinase-defective Lck molecules
      in this system, it failed to stably dephosphorylate kinase-active p56(lck)
      polypeptides. Finally, our studies showed that CD45 was also able to inhibit the
      oncogenic potential of a constitutively activated version of p56(lck) in NIH 3T3
      cells. This effect did not require the Lck unique domain and apparently resulted
      from selective dephosphorylation of substrates of activated p56(lck) in
      fibroblasts. In addition to providing insights into the nature and regulation of
      the interactions between CD45 and p56(lck) in T-cells, these results indicated
      that CD45 clearly has the capacity to both positively and negatively regulate
      p56(lck)-mediated functions in vivo.

PMID- 9139735
TI  - Purification and reconstitution of the vacuolar H+-ATPases from lemon fruits and
      epicotyls.
AB  - The vacuolar H+-ATPases (V-ATPases) of lemon fruits and epicotyls were detergent
      solubilized, purified by column chromatography, and reconstituted into artificial
      proteoliposomes. During purification, a vanadate- and nitrate-sensitive ATPase
      activity, consisting of partially disassembled V-ATPase complexes, was resolved
      from the V-ATPase peak. ATPase and H+-transport activities of the purified,
      reconstituted V-ATPases of both fruit and epicotyl exhibited similar inhibitor
      profiles, except that the fruit V-ATPase retained partial vanadate sensitivity.
      Since the V-ATPase activity of native fruit tonoplast vesicles is insensitive to
      inhibitors (Muller, M. L., Irkens-Kiesecker, U., Rubinstein, B., and Taiz, L.
      (1996) J. Biol. Chem. 271, 1916-1924), membrane lipids or other factors may
      protect the fruit V-ATPase from inactivation in vivo. A kinetic analysis of H+
      pumping and H+-leakage indicated that the reconstituted epicotyl V-ATPase
      exhibited twice as much intrinsic uncoupling or slip as the reconstituted fruit V
      ATPase. Comparison of their subunit compositions by SDS-polyacrylamide gel
      electrophoresis indicated that the reconstituted fruit V-ATPase is enriched in
      two polypeptides of 33/34 and 16 kDa. Moreover, the stalks of negatively stained
      juice sac V-ATPases appeared thicker than those of epicotyl V-ATPases in electron
      micrographs.

PMID- 9139736
TI  - The DNA binding pattern of the retinoid X receptor is regulated by ligand
      dependent modulation of its oligomeric state.
AB  - The retinoid X receptor (RXR) regulates target gene transcription via its
      association with cognate DNA response elements either as a homodimer or as a
      heterodimer with a number of other nuclear receptors. We previously demonstrated
      that, in solution, RXR forms tetramers with a high affinity and that ligand
      binding leads to dissociation of receptor tetramers to smaller species. Here it
      is shown that RXR tetramers form stable complexes with direct repeats (DR-1 or DR
      5) or palindromic (TREpal) response elements. Binding of RXR tetramers to cognate
      DNA occurs with a significantly higher affinity as compared with dimers. Ligand
      binding by DNA-bound RXR tetramers results in their dissociation to DNA-bound
      dimers, a process that is completely reversed upon removal of the ligand.
      Formation of stable tetramer-DNA complexes requires binding of two
      oligonucleotides/tetramer. It is proposed that ligand-dependent modulation of the
      oligomeric state of RXR is a regulatory feature of this nuclear receptor.

PMID- 9139737
TI  - Cleavage site for sterol-regulated protease localized to a leu-Ser bond in the
      lumenal loop of sterol regulatory element-binding protein-2.
AB  - A sterol-regulated protease initiates release of the NH2-terminal segments of
      sterol regulatory element-binding proteins (SREBPs) from cell membranes, thereby
      allowing them to enter the nucleus and to stimulate transcription of genes
      involved in the uptake and synthesis of cholesterol and fatty acids. Using SREBP
      2 as a prototype, we here identify the site of sterol-regulated cleavage as the
      Leu522-Ser523 bond in the middle of the 31-residue hydrophilic loop that projects
      into the lumen of the endoplasmic reticulum and nuclear envelope. This site was
      identified through use of a vector encoding an SREBP-2/Ras fusion protein with a
      triple epitope tag that allowed immunoprecipitation of the cleaved COOH-terminal
      fragment. The NH2 terminus of this fragment was pinpointed by radiochemical
      sequencing after replacement of selected codons with methionine codons and
      labeling the cells with [35S]methionine. Alanine scanning mutagenesis revealed
      that only two amino acids are necessary for recognition by the sterol-regulated
      protease: 1) the leucine at the cleavage site (leucine 522), and 2) the arginine
      at the P4 position (arginine 519). These define a tetrapeptide sequence, RXXL,
      that is necessary for cleavage. Cleavage was not affected when the second
      transmembrane helix of SREBP-2 was replaced with the membrane-spanning region of
      the low density lipoprotein receptor, indicating that this sequence is not
      required for regulation. Glycosylation-site insertion experiments confirmed that
      leucine 522 is located in the lumen of the endoplasmic reticulum. We conclude
      that the sterol-regulated protease is a novel enzyme whose active site faces the
      lumen of the nuclear envelope, endoplasmic reticulum, or another membrane
      organelle to which the SREBPs may be transported before cleavage.

PMID- 9139738
TI  - Characterization of a 180-kDa intestinal epithelial cell membrane glycoprotein,
      gp180. A candidate molecule mediating t cell-epithelial cell interactions.
AB  - Previous studies have shown that normal human intestinal epithelial cells
      stimulate CD8(+) suppressor T cell proliferation in an allogeneic mixed
      epithelial/T cell co-culture system, which is neither restricted by class I or
      class II major histocompatibility complex antigens nor by any soluble factors
      from epithelial cells. Two epithelial specific monoclonal antibodies (mAb), mAb
      B9 and mAb L12, are potent inhibitors of this mixed epithelial/T cell reaction
      but not of conventional mixed lymphocyte reactions. While phenotypically distinct
      by tissue staining, both mAbs recognize a 180-kDa epithelial membrane
      glycoprotein (gp180). Further characterization of gp180 revealed the following.
      1) The protein migrated between 150 and 180 kDa in SDS-polyacrylamide gel
      electrophoresis and could be resolved by Western blot using mAb B9 or mAb L12. 2)
      The molecule has two forms, an apically sorted glycosylphosphatidylinositol
      anchored form and a basolateral transmembrane form. 3) gp180 is heavily N
      glycosylated, since N-glycanase treatment results in a >50% reduction in size. 4)
      Purified gp180 can bind to peripheral blood T cells and activate p56(lck). 5)
      gp180 can activate p56(lck) in 3G8 (a murine T cell hybridoma transfected with
      human CD8alpha cDNA) but not in 3G4 (CD4 transfectant), suggesting that gp180
      binds to CD8. Thus, gp180 appears to be a novel regulator of mucosal immune
      responses.

PMID- 9139739
TI  - ATF-2 and C/EBPalpha can form a heterodimeric DNA binding complex in vitro.
      Functional implications for transcriptional regulation.
AB  - We screened an expression cDNA library with a radiolabeled C/EBPalpha fusion
      protein and isolated three independent cDNAs encoding ATF-2, a bZIP protein that
      binds cAMP response elements (CRE). This interaction requires the respective bZIP
      domains, which form a typical bZIP heterodimer with altered DNA binding
      selectivity. C/EBPalpha and ATF-2 homodimers bind CRE sites, but ATF-2:C/EBPalpha
      heterodimers do not. Heterodimers bind an asymmetric sequence composed of one
      consensus half-site for each monomer, and may thus have a unique regulatory
      function. As predicted, co-transfection of ATF-2 with C/EBPalpha results in
      decreased activation of transcription driven from consensus C/EBP-binding sites.
      In contrast, C/EBPalpha and ATF-2 function cooperatively to activate
      transcription driven by the asymmetric sequence. Both factors are expressed in
      liver, where immunoprecipitation experiments show that ATF-2 co-precipitates with
      C/EBPalpha. These results are consistent with the interpretation that C/EBPalpha
      and ATF-2 can associate in vivo. Moreover, the formation of ATF-2:C/EBPbeta
      heterodimers suggests that cross-family dimerization with ATF-2 may be a general
      property for C/EBP family proteins.

PMID- 9139740
TI  - Alterations in the catalytic activity of yeast DNA topoisomerase I result in cell
      cycle arrest and cell death.
AB  - Eukaryotic DNA topoisomerase I catalyzes the relaxation of supercoiled DNA
      through a concerted mechanism of DNA strand breakage and religation. The
      cytotoxic activity of camptothecin results from the reversible stabilization of a
      covalent enzyme-DNA intermediate. Mutations in two conserved regions of yeast DNA
      topoisomerase I induced a similar mechanism of cell killing, albeit through
      different effects on enzyme catalysis. In Top1T722Ap, substituting Ala for Thr722
      reduced enzyme specific activity by 3-fold, yet enhanced the stability of the
      covalent enzyme-DNA complex. In contrast, Top1R517Gp was 1,000-fold less active
      and camptothecin resistant. Nevertheless, salt-stable DNA-enzyme intermediates
      were detected. Mutation of the active-site tyrosine abrogated mutant enzyme
      activity and cytotoxicity, while sublethal levels of top1T722A expression
      increased rDNA recombination. In checkpoint proficient cells, pGAL1-induced top1
      expression coincided with the accumulation of a terminal G2-arrested phenotype.
      Although the acquisition of this phenotype did not require Rad9p, Top1R517Gp- and
      Top1T722Ap-induced lethality was enhanced in rad9Delta strains. Thus, despite
      mechanistic differences between Top1R517Gp and Top1T722Ap, the DNA lesions
      resulting from the enhanced stability of the covalent enzyme-DNA intermediates
      were sufficient to cause cell cycle arrest and cell death.

PMID- 9139741
TI  - Characterization of retinoic acid-induced AP-1 activity in B16 mouse melanoma
      cells.
AB  - Retinoic acid (RA) induces differentiation of B16 mouse melanoma cells, which is
      accompanied by an increase in protein kinase Calpha (PKCalpha) as well as a
      selective enrichment of nuclear PKCalpha. We report here that RA also increases
      AP-1 activity in these cells. Transient transfection of B16 cells with luciferase
      reporter gene constructs indicated that RA induced a concentration-dependent
      increase in AP-1 activity. Acute treatment (2 h) of B16 cells with phorbol
      dibutyrate (PDB) increased AP-1 activity by 10-fold. RA treatment did not change
      the expression of Jun family members; however, it decreased the expression of c
      Fos. In contrast acute PDB treatment induced c-Fos expression, while having
      little effect on c-Jun. Five DNA-protein complexes were formed with nuclear
      extracts from B16 cells and an oligonucleotide containing an AP-1 consensus
      sequence. Several complexes were decreased in cells treated with RA. Conversely,
      certain complexes were increased in cells acutely treated with PDB. The slowest
      migrating complexes were shown to contain Fos family members. Down-regulation of
      PKC inhibited both the acute PDB-induced and the RA-induced increase in AP-1
      activity. The selective PKC enzyme inhibitor, bisindolylmaleimide, reduced PDB
      stimulated AP-1 activity, but enhanced RA-induced AP-1 activity. These results
      together with our previous studies suggest the intriguing possibility that PKC
      protein, but not enzyme activity, may be required for RA-induced AP-1 activity.

PMID- 9139742
TI  - DNA topoisomerases regulate R-loop formation during transcription of the rrnB
      operon in Escherichia coli.
AB  - Recent in vivo and in vitro studies have suggested an important role for DNA
      topoisomerases in regulating R-loop formation during transcription in Escherichia
      coli. In the present report we present genetic and biochemical evidence strongly
      suggesting that R-loop formation can occur during transcription of a portion of
      the rrnB operon and that it is regulated by DNA topoisomerase activity. We found
      that a multicopy plasmid (pBR322) carrying an heavily transcribed portion of the
      rrnB operon cannot be transformed in topA mutants unless RNase H is overproduced.
      Transcription of the 567-base pair HindIII fragment from the rrnB operon allows
      the extraction of large amount of R-looped plasmid DNAs from a topA mutant, in a
      manner that depends on the intracellular level of RNase H activity. When DNA
      gyrase is sufficiently active, hypernegatively supercoiled plasmid DNA is
      produced if the same DNA fragment is transcribed in a topA mutant. The formation
      of such topoisomers most likely reflect the presence of extensive R-loops since
      it is sensitive to the intracellular level of RNase H activity. Finally, the
      formation of R-looped plasmid DNAs in an in vitro transcription system using
      phage RNA polymerases is also detected when the 567-base pair HindIII fragment is
      transcribed on a negatively supercoiled DNA template.

PMID- 9139743
TI  - Reconstitution of yeast and Arabidopsis RNA polymerase alpha-like subunit
      heterodimers.
AB  - Two subunits of about 36-44 kDa and 13-19 kDa in the eukaryotic nuclear RNA
      polymerases share limited amino acid sequence similarity to the alpha subunit in
      Escherichia coli RNA polymerase. The alpha subunit in the prokaryotic enzyme has
      a stoichiometry of 2, but the stoichiometry of the alpha-like subunits in the
      eukaryotic enzymes is not entirely clear. To gain insight into the subunit
      stoichiometry and assembly pathway for eukaryotic RNA polymerases, in vitro
      reconstitution experiments have been carried out with recombinant alpha-like
      subunits from yeast and plant RNA polymerase II. The large and small alpha-like
      subunits from each species formed stable heterodimers in vitro, but neither the
      large or small alpha-like subunits formed stable homodimers. Furthermore, mixed
      heterodimers were formed between corresponding subunits of yeast and plants, but
      were not formed between corresponding subunits in different RNA polymerases from
      the same species. Our results suggest that RNA polymerase II alpha-like
      heterodimers may be the equivalent of alpha homodimers found in E. coli RNA
      polymerase.

PMID- 9139744
TI  - Ferritin is a developmentally regulated nuclear protein of avian corneal
      epithelial cells.
AB  - Previously, we generated monoclonal antibodies against chicken corneal cells
      (Zak, N. B., and Linsenmayer, T. F. (1983) Dev. Biol. 99, 373). We have now
      observed that one group of these antibodies reacts with a developmentally
      regulated component of corneal epithelial cell nuclei. This component is the
      heavy chain of ferritin, as determined by analyses of immunoisolated cDNA clones
      and immunoblotting of the protein. Immunoblotting also suggests that the nuclear
      ferritin may be in a supramolecular form that is similar to the iron-binding
      ferritin complex found in the cytoplasm of many cells. In vitro cultures and
      transfection studies show that the nuclear localization depends predominantly on
      cell type but can be altered by the in vitro environment. The appearance of
      nuclear ferritin is at least partially under translational regulation, as is
      known to be true for the cytoplasmic form of the molecule. The tissue and
      developmental distributions of the mRNA for the molecule are much more extensive
      than the protein itself, and the removal of iron from cultures of corneal
      epithelial cells with the iron chelator deferoxamine prevents the appearance of
      nuclear ferritin. At present the functional role(s) of nuclear ferritin remain
      unknown, but previous studies on cytoplasmic ferritin raise the possibility that
      it prevents damage due to free radical generation ("oxidative stress") by
      sequestering iron. Although it remains to be tested whether nuclear ferritin
      prevents oxidative damage, we find this an attractive possibility. Since the
      corneal epithelium is transparent and is constantly exposed to free radical
      generating UV light, it is possible that the cells of this tissue have evolved a
      specialized mechanism to prevent oxidative damage to their nuclear components.

PMID- 9139745
TI  - Regulated unmasking of in vivo synthesized maternal mRNA at oocyte maturation. A
      role for the chaperone nucleoplasmin.
AB  - We examine the translational regulation of histone H4 mRNA when Xenopus laevis
      oocytes are induced to mature with progesterone. Histone H4 mRNA synthesized from
      plasmid templates microinjected into oocyte nuclei is translationally silenced
      (masked). This masked mRNA becomes translationally active only after oocyte
      maturation. In contrast, histone H4 mRNA injected into the oocyte cytoplasm is
      translationally active both before and after oocyte maturation. Thus,
      transcription in vivo is required to mask histone H4 mRNA and to allow subsequent
      translational regulation. Protein association with histone H4 mRNA synthesized in
      vivo was determined before and after oocyte maturation. UV cross-linking of
      radiolabeled RNA to protein and immunoprecipitation of cross-linked proteins
      reveals an increased association of the chaperone nucleoplasmin with
      ribonucleoprotein particles dependent on the oocyte maturation process. The Y-box
      protein FRGY2 inhibits translation of histone H4 mRNA in vitro. Nucleoplasmin is
      able to partially relieve this repression. We discuss the potential role of
      nuleoplasmin in the remodeling of repressive ribonucleoprotein particles
      containing maternal mRNA to facilitate translational activation.

PMID- 9139746
TI  - Unique structural features of a novel class of small heat shock proteins.
AB  - Small heat shock proteins (smHSPs) and alpha-crystallins constitute a family of
      related molecular chaperones that exhibit striking variability in size, ranging
      from 16 to 43 kDa. Structural studies on these proteins have been hampered by
      their tendency to form large, often dynamic and heterogeneous oligomeric
      complexes. Here we describe the structure and expression of HSP12.6, a member of
      a novel class of smHSPs from the nematode Caenorhabditis elegans. Like other
      members of its class, HSP12.6 possesses a conserved alpha-crystallin domain but
      has the shortest N- and C-terminal regions of any known smHSP. Expression of
      HSP12.6 is limited to the first larval stage of C. elegans and is not
      significantly up-regulated by a wide range of stressors. Unlike other smHSPs,
      HSP12.6 does not form large oligomeric complexes in vivo. HSP12.6 was produced in
      Escherichia coli as a soluble protein and purified. Cross-linking and
      sedimentation velocity analyses indicate that the recombinant HSP12.6 is
      monomeric, making it an ideal candidate for structure determination.
      Interestingly, HSP12.6 does not function as a molecular chaperone in vitro, since
      it is unable to prevent the thermally induced aggregation of a test substrate.
      The structural and functional implications of these findings are discussed.

PMID- 9139747
TI  - Stimulation of glucose-6-phosphatase gene expression by glucose and fructose-2,6
      bisphosphate.
AB  - Glucose-6-phosphatase, a key enzyme in the homeostatic regulation of blood
      glucose concentration, catalyzes the terminal step in gluconeogenesis and
      glycogenolysis. Glucose, the product of the glucose-6-phosphatase reaction,
      dramatically increases the level of glucose-6-phosphatase mRNA transcripts in
      primary hepatocytes (20-fold), and the maximum response is obtained at a glucose
      concentration as low as 11 mM. Glucose specifically increases glucose-6
      phosphatase mRNA and L-type pyruvate kinase mRNA. In the rat hepatoma-derived
      cell line, Fao, glucose increases the glucose-6-phosphatase mRNA only modestly (3
      fold). In the presence of high glucose concentrations, overexpression of
      glucokinase in Fao cells via recombinant adenovirus vectors increases lactate
      production to the level found in primary hepatocytes and increases glucose-6
      phosphatase gene expression by 21-fold. Similar overexpression of hexokinase I in
      Fao cells with high levels of glucose does not increase lactate production nor
      does it change the response of glucose-6-phosphatase mRNA to glucose. Glucokinase
      overexpression in Fao cells blunts the previously reported inhibitory effect of
      insulin on glucose-6-phosphatase gene expression in these cells. Raising the
      cellular concentration of fructose-2,6-bisphosphate, a potent effector of the
      direction of carbon flux through the gluconeogenic and glycolytic pathways, also
      stimulated glucose-6-phosphatase gene expression in Fao cells. Increasing the
      fructose-2,6-bisphosphate concentration over a 15-fold range (12 +/- 1 to 187 +/-
      17 pmol/plate) via an adenoviral vector overexpression system, led to a 6-fold
      increase (0.32 +/- 0. 03 to 2.2 +/- 0.33 arbitrary units of mRNA) in glucose-6
      phosphatase gene expression with a concomitant increase in glycolysis and a
      decrease in gluconeogenesis. Also, the effects of fructose-2, 6-bisphosphate
      concentrations on fructose-1,6-bisphosphatase gene expression were stimulatory,
      leading to a 5-6-fold increase in mRNA level over a 15-fold range in fructose-2,6
      bisphosphate level. Liver pyruvate kinase and phosphoenolpyruvate carboxykinase
      mRNA were unchanged by the manipulation of fructose-2,6-bisphosphate level.

PMID- 9139748
TI  - Expression of transforming growth factor beta (TGFbeta) type III receptor
      restores autocrine TGFbeta1 activity in human breast cancer MCF-7 cells.
AB  - While transforming growth factor beta (TGFbeta) type III receptor (RIII) is known
      to increase TGFbeta1 binding to its type II receptor (RII), the significance of
      this phenomenon is not known. We used human breast cancer MCF-7 cells to study
      the role of RIII in regulating autocrine TGFbeta1 activity because they express
      very little RIII and no detectable autocrine TGFbeta activity. A tetracycline
      repressible RIII expression vector was stably transfected into this cell line.
      Expression of RIII increased TGFbeta1 binding to TGFbeta type I receptor (RI) as
      well as RII. Treatment with tetracycline suppressed RIII expression and abolished
      TGFbeta1 binding to RI and RII. Growth of RIII-transfected cells was reduced by
      40% when plated at low density on plastic. This reduction was reversed by
      tetracycline treatment and was partially reversed by treatment with a TGFbeta1
      neutralizing antibody. The activity of a TGFbeta-responsive promoter construct
      when transiently transfected was more than 3-fold higher in the RIII-transfected
      cells than in the control cells. Treating the cells with tetracycline or the
      TGFbeta1 neutralizing antibody also significantly attenuated the increased
      promoter activity. These results suggest that expression of RIII restored
      autocrine TGFbeta1 activity in MCF-7 cells. The RIII-transfected cells were also
      much less clonogenic in soft agarose than the control cells indicating a
      reversion of progression. Thus, RIII may be essential for an optimal level of the
      autocrine TGFbeta activity in some cells, especially in the transformed cells
      with reduced RII expression.

PMID- 9139749
TI  - Insulin receptor substrate (IRS)-2 is dephosphorylated more rapidly than IRS-1
      via its association with phosphatidylinositol 3-kinase in skeletal muscle cells.
AB  - Insulin receptor substrate (IRS)-2 is structurally and functionally similar to
      IRS-1. Indeed, stimulation with insulin or insulin-like growth factor I led to
      the rapid tyrosine phosphorylation of both IRS-1 and IRS-2, which in turn
      activated phosphatidylinositol (PI) 3-kinase in L6 cells and rat skeletal muscle.
      However, IRS-2 was rapidly dephosphorylated (3-10 min after the addition of
      insulin/insulin-like growth factor I), whereas IRS-1 phosphorylation continued
      for at least 60 min. The time courses of the PI 3-kinase activity associated with
      IRS-1 and IRS-2 paralleled the tyrosine phosphorylation of these proteins.
      Preincubation with sodium orthovanadate, an inhibitor of protein tyrosine
      phosphatase, blocked the rapid dephosphorylation of IRS-2, suggesting the
      involvement of tyrosine phosphatase. The activation of PI 3-kinase apparently
      plays an important role in the rapid dephosphorylation of IRS-2, as IRS-2
      dephosphorylation was inhibited markedly by suppressing PI 3-kinase activity with
      wortmannin or overexpression of the dominant negative p85 subunit of PI 3-kinase,
      which cannot bind the p110 catalytic subunit. In addition, platelet-derived
      growth factor stimulation prior to insulin stimulation decreased IRS-associated
      PI 3-kinase and significantly inhibited the dephosphorylation of IRS-2. Taken
      together, these observations suggest that IRS-2 plays a unique role in mediating
      the signals from the insulin receptor to downstream molecules and that this
      effect is more transient than that of IRS-1. Tyrosine phosphatase and IRS
      associated PI 3-kinase activity thus contribute to the rapid dephosphorylation of
      IRS-2.

PMID- 9139750
TI  - The spinach chloroplast endoribonuclease CSP41 cleaves the 3'-untranslated region
      of petD mRNA primarily within its terminal stem-loop structure.
AB  - 3'-Untranslated region stem-loop structures are major determinants of chloroplast
      mRNA stability. The 3' stem-loop region of spinach petD precursor mRNA (pre
      mRNA), a chloroplast gene encoding subunit IV of the cytochrome b6.f complex,
      forms a stable RNA-protein complex in vitro with chloroplast stem-loop binding
      proteins (CSPs) of 55, 41, and 29 kDa. We have previously purified CSP41 and
      cloned the corresponding cDNA. In vitro studies demonstrated that CSP41 is a
      bifunctional protein that displays both endoribonuclease and RNA-binding
      activities. In this work, the RNase activity of CSP41 is further characterized
      using the bacterially expressed protein. Our data show that CSP41 cleaves both
      single-stranded and double-stranded RNAs but not DNA. However, it exhibits a
      preference for stem-loop-containing RNAs. When the 3'-untranslated region of petD
      pre-mRNA is provided as a substrate, CSP41 specifically cleaves it within the
      stem-loop region, implying that CSP41 has an important role in the control of
      petD mRNA stability. Our data also show that the sequence-specific RNA-binding
      activity of CSP41 affects the rate, but not the specificity, of its RNase
      activity, suggesting that CSP41 is probably involved in other events of
      chloroplast RNA metabolism in addition to RNA degradation. By analyzing C
      terminal deletions of CSP41, the RNase domain was located between amino acid
      residues 73 and 191.

PMID- 9139751
TI  - Essential fatty acids, immune function, and exercise.
AB  - The immunologic response to exercise comprises numerous alterations within the
      immune system, but how these processes are regulated is still largely unknown.
      Exercise-related immunological changes include signs of inflammation, such as
      release of inflammatory mediators, activation of various white blood cell lines
      and complement, and induction of acute phase proteins. Nevertheless, signs of
      immunosuppression, such as decreased T and B cell function or impaired cytotoxic
      or phagocytic activity, can also be observed. Some data suggest that essential
      fatty acids help regulate inflammatory processes, modulating both cytokine
      release and the acute phase response. Positive effects of changing dietary
      essential fatty acids have been demonstrated in chronic inflammatory diseases. In
      contrast, little is known about the contribution of fatty acids to the exercise
      induced immunologic reaction. Essential fatty acids may determine alterations
      within the immune system following exercise. Therefore, future studies are
      necessary to evaluate the influence of the fatty acid composition on the
      inflammatory or immunosuppressive component following heavy exertion.

PMID- 9139752
TI  - Vitamin C, neutrophil function, and upper respiratory tract infection risk in
      distance runners: the missing link.
AB  - Moderate submaximal exercise results in neutrophilia and enhanced phagocytic and
      oxidative capacity of neutrophils. It has been hypothesized, however, that during
      intensive exercise and periods of intensive training this pro-oxidative effect
      becomes suppressive. Vitamin C is widely recognized for its antioxidant function
      in extracellular fluid, and it has been shown to neutralize O2-, HOCl, and .OH
      and to attenuate the suppression of phagocytic function. Clinical manifestation
      of reduced neutrophil function following participation in ultramarathon races
      has, however, not been observed. Although neutrophils constitute 50-60% of
      leukocytes and although they are the first line of defense to bacteriological
      invasion, postrace episodes of upper respiratory tract infection (URTI) are not
      correlated with a decrement in the function of this individual parameter of
      immune function. The efficacy of Vitamin C supplements in reducing the incidence
      of postrace URTI symptoms, therefore, cannot be fully explained at this stage.

PMID- 9139753
TI  - Autoimmune disorders, physical activity, and training, with particular reference
      to rheumatoid arthritis.
AB  - Rheumatoid arthritis arises from a reaction of the immune system to normal body
      components, sometimes triggered by bacterial or viral infection. The synovia of
      affected joints are infiltrated by CD4+, CD19-, and plasma cells. The synovial
      fluid shows a sterile inflammation, with high neutrophil counts and increased
      concentrations of proinflammatory cytokines (particularly IL-1, IL-8, TNF-alpha
      and JFN-gamma). The plasma shows increased CD4+ counts and a pro-inflammatory
      shift in T cell populations with high titers of rheumatoid factors. Traditional
      treatment has included rest of the affected part, which can cause a reduction of
      physical condition. However, exercise induces changes in circulating immune
      function (including a decrease of CD4+ count) that would appear helpful in
      regulating inflammation. Further, there is evidence that patients can tolerate a
      program of regular moderate aerobic exercise. Moreover, empirical data suggest
      that such a prescription substantially enhances physical performance, without
      exacerbating either clinical or immunological markers of the disease process.

PMID- 9139754
TI  - Aging, exercise, training, and the immune system.
AB  - Human immune function undergoes adverse changes with aging, including development
      of a relative immune deficiency and an immune dysregulated state. The T cells
      show the largest age-related differences in distribution and function. The
      antibody production capacity of B cells also shows an age-related decline. Acute
      bouts of exercise modulate many immune parameters as seen in peripheral blood.
      With regard to NK cell activity, a single bout of moderate exercise seems to be
      well tolerated by the elderly, and the resting NK cell activity of elderly
      subjects seems to increase with training. Cross-sectional comparisons of immune
      status imply that habitual physical activity may enhance NK cell activity and
      check certain aspects of the age-related decline in T cell function. Future
      studies are required to clarify whether such long-term exercise and resulting
      improvements of immune function give rise to any beneficial effects on
      infections, malignancies, and autoimmune disorders.

PMID- 9139755
TI  - Exercise, training, and neutrophil function.
AB  - Although neutrophils are critical to host defense, they are also involved in the
      pathology of various inflammatory diseases. Neutrophils, representing 60% of
      circulating leukocytes in human subjects, are readily accessible to experimental
      investigation. Discrete aspects of, neutrophil function can be quickly and
      accurately assessed in vitro using a variety of techniques that involve
      assessment of intracellular and extracellular functional activities. Moderate
      exercise has variable effects on neutrophil function, but intense exercise is
      potentially immunosuppressive. Endurance training also suppresses most neutrophil
      functions chronically. A greater understanding of some fundamental aspects of
      neutrophil function and the uncovering of newly defined roles underlines
      potential applications in general and sports medicine. However, the practical
      value of this knowledge for monitoring the health and training programs of elite
      athletes requires further clarification. The current knowledge of neutrophil and
      immune functional measurements has not progressed to an extent that routine
      profiling in athletes can be used diagnostically.

PMID- 9139756
TI  - Telemedicine in northern Norway.
AB  - The University Hospital of Tromso has been involved in a variety of telemedicine
      activities since the late 1980s, including teleradiology, telepathology,
      teledermatology, remote endoscopy, remote gastroscopy, teleechocardiography,
      transmission of electrocardiograms, telepsychiatry, electronic delivery of
      laboratory results and distance learning for health professionals. Since 1993 the
      department of telemedicine in Tromso has been designated the national centre of
      competence in telemedicine. With a wealth of experience to draw from, a critical
      number of health-care professionals exposed to and using telemedicine routinely,
      the support of the Norwegian health authoriues, a national centre guiding
      telemedicine research, no licensing barriers within the country, nationwide ISDN
      and reimbursement for telemedicine services, the future of telemedicine in Norway
      looks promising.

PMID- 9139757
TI  - The possible use of telemedicine in developing countries.
AB  - Telemedicine may be a useful technique for delivering health care in the
      developing world. However, there is little practical experience to draw on and
      real concerns that if additional resources were to become available telemedicine
      might not be the most appropriate use for them. The logical steps to determine
      the place of telemedicine in the developing world therefore appear to be: (1) to
      identify potential telemedicine projects-the Telecommunication Development Bureau
      of the International Telecommunication Union is trying to do this and has
      recently sponsored missions to various countries in Africa and Asia; (2) to carry
      out properly controlled pilot projects in order to demonstrate technical
      feasibility and to quantify the benefits to the healthcare system; (3) to
      calculate the costs of large-scale deployment. Assuming that telemedicine is
      shown to be beneficial, it is only at this final stage that a rational decision
      can be made about whether telemedicine would be an appropriate use of additional
      resources in a developing country, as opposed to alternative uses of those
      resources to solve other important problems of health care.

PMID- 9139758
TI  - Medical decision support for remote general practitioners using telemedicine.
AB  - A telemedicine link was set up between the casualty department of a remote
      community hospital and the accident and emergency department of a large urban
      hospital. The telemedicine link comprised teleradiology, videoconferencing and
      telepresence. The system was connected by ISDN (128 kbit/s) and also by a
      satellite link (64 kbit/s). During a one-year clinical trial, 120
      teleconsultations took place between the community hospital and the specialist
      trauma centre, 110 using ISDN and 10 using the satellite link. Teleradiology was
      used in 116 teleconsultations, videoconferencing in 76, and telepresence in four.
      Survey results indicated that both the general practitioners running the
      community hospital and accident and emergency consultants felt that
      teleconsultation had improved patient care. Communication between clinicians
      using the telemedicine link avoided the transfer of 70 patients, representing an
      estimated cost saving of Pounds 65,000.

PMID- 9139759
TI  - A cost analysis of an emergency computerized tomography teleradiology system.
AB  - We carried out a cost analysis of a teleradiology system for emergency
      computerized tomography (CT) examinations. Teleradiology was implemented by
      connecting two spiral CT scanners in the University Hospital in Innsbruck and the
      Regional Hospital in Zwettl. It enabled the remote hospital in Zwettl to get fast
      and competent reports of emergency CT examinations when there was no specialist
      radiologist available. In 13 months' use for routine night and weekend service,
      the system proved fast and reliable. During the study period 121 emergency
      examinations of 116 patients were transmitted from Zwettl to Innsbruck. The fixed
      costs of teleradiology were for the ISDN connection and amounted to DM230 plus
      DM696/year rental. The average cost of one emergency CT examination by
      teleradiology was DM372 (range 308-453). One possible alternative, transporting
      the films by taxi for reporting elsewhere, was cheaper (estimated cost DM156),
      but would have been much slower. Another alternative, transporting the patient to
      the nearest central hospital for scanning, was much more expensive: DM524 by road
      or DM4667 by helicopter ambulance.

PMID- 9139760
TI  - Use of the new media for medical education.
AB  - The use of an advanced communication network for education has been an integral
      part of practice at the Mayo Clinic since 1986. The network has been used for
      patient care, research coordination and administrative support, as well as for
      educational programming. In 1994, 2655 hours were broadcast by satellite. There
      were 42,292 participants, representing a total of 47,364 contact hours. Over half
      of this activity was educational. In using the satellite system, a number of
      background support systems have been found to be essential to effective
      communication. First, highly trained technical staff are required to support the
      communication system. Second, presenters require formal training in adapting
      audiovisual materials, such as slides and transparencies, to broadcast media.
      Third, as use of the system has grown, scheduling and prioritizing among the many
      users has become an increasingly time-consuming and challenging task.

PMID- 9139761
TI  - Intercontinental postmortem studies using interactive television.
AB  - For cultural reasons, medical students in the United Arab Emirates (UAE) are not
      offered postmortem studies. In a collaborative project between the medical
      schools of Aberdeen University and the UAE University the feasibility,
      acceptability and effectiveness of telepathology teaching were evaluated. The
      transmission of postmortem video images at a quality high enough for teaching
      purposes was achieved at a data transmission speed of 384 kbit/s.
      Videoconferencing as a method of presentation was viewed by the students as both
      interesting and useful. All students participating in the telepathology teaching
      sessions exceeded the minimum acceptable score of 60% in a multiple-choice
      examination. Although international videoconferencing at 384 kbit/s is expensive,
      the costs involved in the telepathology project were small in relation to the
      educational benefits.

PMID- 9139762
TI  - AUDIOMAT: an electronic newspaper for visually impaired people.
AB  - Electronic newspapers are now becoming available via wide-area computer networks,
      such as the internet. Unfortunately, the Windows-based graphical user interface
      of the client programs makes it difficult for visually impaired people to use
      such services. Furthermore, few visually impaired people have a PC. The AUDIOMAT
      project was designed to provide a reading system for the visually impaired, thus
      giving this community in the Campania region of southern Italy the opportunity to
      read their local newspaper. In a pilot trial, three blind subjects used the
      AUDIOMAT system daily for two months. Despite some minor technical problems the
      system performed well and a wider validation phase is now planned.

PMID- 9139764
TI  - Teledermatology trial in Finland.

PMID- 9139765
TI  - Asthma.

PMID- 9139763
TI  - Use of telecommunications in a rural emergency. Brain surgery by fax.

PMID- 9139766
TI  - Asthma.

PMID- 9139767
TI  - Mechanisms of asthma.
AB  - Understanding of the mechanisms of asthma has progressed in three areas: the
      genetics of asthma, the role of nitric oxide in asthma, and the role of
      neurokinins in asthma. Genes encoding for the high affinity IgE receptor, the
      beta 2-adrenergic receptor, and interleukin-4 have been linked to clinical
      characteristics of asthma. Exhaled nitric oxide may be a useful clinical marker
      for airway inflammation in asthma. Tachykinin receptors are present in human lung
      and may be differentially expressed in individuals with asthma.

PMID- 9139768
TI  - Bronchodilators: new drugs and controversies.
AB  - After complete abstinence, regular use of short-acting beta 2-agonists results in
      an increase in early and late asthmatic (allergen) response, exercise-induced
      bronchoconstriction, and nonspecific airways responsiveness (methacholine).
      Regular use of long-acting beta 2-agonists also results in increased nonspecific
      airways responsiveness (methacholine) with or without concomitant inhaled
      corticosteroids and attenuates the response to escalating doses of inhaled short
      acting beta 2-agonists such as might be used in an acute exacerbation. In spite
      of these findings, symptom control and bronchodilation are improved more with the
      addition of salmeterol than with a doubling of inhaled corticosteroid dose.
      Selective cyclic nucleotide phosphodiesterase inhibitors show promise in
      expanding the bronchodilator and anti-inflammatory effects of theophylline.

PMID- 9139769
TI  - Alternative treatments in the patient with intractable asthma.
AB  - Various medications have been suggested as alternative therapy for oral
      corticosteroids in the treatment of asthma, due to the known adverse effects of
      oral corticosteroids. Examples of such medications include methotrexate, gold,
      cyclosporin A, hydroxychloroquine, and dapsone, all of which have a significant
      side-effect profile. Intravenous gammaglobulin therapy used as an immuno
      modulator has little if any side-effects, but it is very costly. The
      antileukotrienes represent a safe class of medications that may be of particular
      benefit to certain subgroups of asthmatic patients. Antileukotrienes have become
      commercially available in other countries.

PMID- 9139770
TI  - Experimental treatments for asthma.
AB  - There has been increased recognition of the importance of inflammatory cells and
      their products in the pathogenesis of asthma. From this recognition has evolved a
      number of new approaches to treat the various components of the asthmatic
      inflammatory response. Nonselective anti-inflammatory agents such as cyclosporine
      and gold appear to decrease symptoms and allow a steroid-sparing effect in many
      cases, though side effects from cyclosporine often necessitate dose reduction.
      Novel oral compounds as the 5-lipoxygenase inhibitors have been effective in
      controlling asthma symptoms triggered by various stimuli, and the cysteinyl
      leukotriene receptor antagonists have shown promise in this regard as well.
      Neurokinin antagonists, inhaled loop diuretics, and lidocaine may play
      significant roles in asthma therapy through inhibition of neurogenic inflammation
      and possibly mast cell function. Inhibition of mast cell products by existing
      drugs such as heparin or the development of specific inhibitors of mast cell
      tryptase may also be effective agents, as are selective phosphodiesterase
      inhibitors, which appear to have anti-inflammatory properties. Finally, specific
      cytokine antagonists, agonists, inhibitors of T-cell function, selective
      inducible nitric oxide synthase inhibitors, and even gene-directed strategies may
      provide not only insights into the pathogenesis of asthma but also novel
      therapeutic approaches to treat the inflammation in this disease.

PMID- 9139771
TI  - New developments in the immunology of asthma, with a focus on mechanisms and
      treatment.
AB  - Asthma is a chronic inflammatory disease of the airways involving the activation
      of many different cell types. The immunologic basis of asthma is widely accepted
      for allergic asthma, and the synthesis of IgE is dependent on cytokines. A
      process of healing and repair follows on from inflammation and this leads to a
      variable degree of remodelling of the airways. The treatment of asthma should
      take into account that the disease is associated with short-lived symptoms that
      can be prevented or reversed by bronchodilators, exacerbations that can be
      treated or reversed by anti-inflammatory drugs, and remodelling of the airways,
      for which no definite treatment has yet been validated.

PMID- 9139772
TI  - National and international guidelines for the diagnosis and treatment of asthma.
AB  - Excellent guidelines on the management of asthma are now available. The most
      comprehensive guidelines developed recently are the National Heart, Lung, and
      Blood Institute (NHLBI) Guidelines for the Diagnosis and Management of Asthma,
      the NHLBI/World Health Organization Global Initiative for Asthma, and the
      American Academy of Allergy, Asthma and Immunology and American College of
      Allergy, Asthma and Immunology Practice Parameters for the Diagnosis and
      Treatment of Asthma. The main purpose of such guidelines is to improve the
      quality of care for patients with asthma. This can only be accomplished, however,
      if these documents are used effectively.

PMID- 9139773
TI  - Asthma in the managed care setting.
AB  - The quality improvement techniques of managed care are dramatically upgrading the
      delivery of asthma education and therapy, yielding cost-effective outcomes
      through a variety of approaches. Guidelines have been available in national and
      international references, but successful implementation outside of managed care
      has been poor. The complex components known to produce success in asthma care
      have not been properly reimbursed in the fee-for-service tradition. Even within
      managed care settings, attention to cost-effectiveness varies widely, and
      creative new approaches promise better returns than early asthma programs. Tools
      that managed care can offer for improved asthma outcomes and cost-effective
      options are presented.

PMID- 9139774
TI  - Why is asthma becoming more of a problem?
AB  - From antiquity to the 1920s, the frequency of asthma and especially death from
      asthma was considered to be rare. In fact, asthma was not considered a
      significant cause of death during the early years of the 20th century. The
      Frenchman Armand Trousseau declared in his Clinique Medicale that "asthma n'est
      pas fatale" ("asthma is not fatal"). In the United States, Oliver Wendell Holmes
      had described asthma as a "slight ailment that promotes longevity." Clearly this
      perception of asthma has changed for many reasons. It has been only in the past
      10 years that death from asthma has received increased attention when evidence
      was obtained that the rate was increasing. Few reports of asthma death had
      appeared until the late 1950s. Mortality today is disproportionately high for
      asthmatic patients aged 5 through 34 years. Asthma mortality rates have increased
      worldwide. Substantial increases in the rates of death from asthma in patients
      aged 5 through 34 years between the mid-1970s and the mid-1980s had been
      reported. Although asthma is still a relatively infrequent cause of death, it is
      nonetheless important to emphasize that the rates of death from asthma have risen
      in England and Wales, Australia, Canada, the Netherlands, Sweden, France, West
      Germany, Israel, the United States, and Denmark. This review attempts to put this
      data in perspective and to highlight some features, including pollution and
      treatment, that may contribute to this alarming problem.

PMID- 9139775
TI  - Alternative therapies for asthma.
AB  - Many traditional drugs and techniques are gaining popularity in the treatment of
      asthma, although scientific proof of their value is usually inadequate.
      Alternative remedies, including herbs and nonmedication management techniques,
      have not been shown to be useful primary measures, but they still appeal to
      patients who feel unsatisfied with orthodox medicines. Dietary modification may
      be worth considering; evidence suggests that salt reduction and magnesium
      supplementation have value in reducing asthmatic symptoms. The evidence on the
      role of steroid-sparing agents is not encouraging, but administering steroids
      once a day in the mid-afternoon may provide benefit. New aerosol techniques are
      appearing, but judgement is needed to select the best device for each medication
      as well as for each patient.

PMID- 9139776
TI  - Special problems of the asthmatic patient.
AB  - Environmental factors and physical activity present special problems for the
      asthmatic patient. Bronchoconstriction due to workplace exposure is one of the
      most common forms of occupational lung disease and has similar pathogenic
      mechanisms to nonoccupational asthma. Diagnosing occupational asthma may be
      difficult because the association between symptoms during or after work and a
      causative agent may be obscure. Nevertheless, it is important to recognize
      occupational asthma because even trace amounts of the causative agent may trigger
      bronchoconstriction, and the affected employee must almost always avoid exposure.
      Bronchoconstriction induced by exercise has affected the lifestyles of many
      asthmatic patients and has created special problems for numerous accomplished
      athletes. Although exercise-induced asthma (EIA) characteristically occurs
      immediately after cessation of exertion, a recent study suggests that it may
      sometimes begin during sustained exertion. Asthmatic patients who participate in
      winter sports are particularly susceptible to EIA. Vocal cord dysfunction in
      athletes who participate in intense competition can mimic EIA. In addition to
      beta-agonists used immediately before exercise, newer drugs that show promise in
      the treatment of EIA include the leukotriene inhibitors and furosemide. Asthmatic
      patients are susceptible to extremes in atmospheric pressure and have increased
      risk of barotrauma and arterial gas embolism during scuba diving. During longer
      stays at high altitude, however, asthmatic patients appear to have attenuated
      bronchial responsiveness.

PMID- 9139777
TI  - [Helicobacter pylori infection and gastric secretion].

PMID- 9139778
TI  - [Endoscopic treatment of chronic pancreatitis].

PMID- 9139779
TI  - [Morphologic changes of gastric mucosa in Helicobacter pylori infection in
      patients with peptic ulcer disease and chronic gastritis].
AB  - The present study was carried out to value the histological method of detection
      of Helicobacter pylori in gastric mucosa and to analyse the pathological changes
      of the Helicobacter pylori-positive patients with duodenal and gastric ulcer and
      with chronic gastritis. The studies population consisted of 150 patients, 76 F
      and 74 M. The samples were taken during gastroscopy from the prepyloric region
      and gastric body. After routine histological procedure they were stained HE and
      by Giemsa method for detection of H.pylori. The latter was identified in 56.6% of
      of the patients with duodenal ulcer, in 54.8% of those with gastric ulcer, in
      17.6% of the patients after partial gastrectomy and in 46.9% of patients
      suffering from chronic gastritis. The increased density of H.pylori (third grade)
      was detected in the cases with clinical diagnosis of duodenal and gastric ulcer
      and erythematous endoscopic gastritis and was correlated with the histological
      picture of chronic active gastritis, which was characterized by diffuse mixed
      cellular exudation, lesion of the superficial epithelial, mucosal erosions and by
      foveolar hyperplasia. We suggest that this morphological picture corresponded to
      the active phase of Helicobacter infection. We conclude, that the histological
      method by Giemsas staining is effective especially in the acute phase of H.pylori
      infection and represents high diagnostic value and may be used in monitoring
      during the antibacterial (anti H.pylori) treatment. There is the correlation
      between massive density of H.pylori observed in gastric mucosa and chronic active
      gastritis.

PMID- 9139780
TI  - [Changes in gastric mucosa and Helicobacter pylori infection in young health
      volunteers].
AB  - They examined 114 young health volunteers to establish a frequency of
      inflammation of gastric mucous membrane and(or) duodenal bulbous, a frequency of
      Helicobacter pylori infection and interdependence between infection and
      inflammation, smoking and nourishment. They evaluated a frequency and intensity
      of inflammation in antrum, fundus and duodenal bulbus and present of Helicobacter
      pylori using an urease test and microscopic examination. They noted in young
      inhabitants of Warsaw, appearance of asymptomatic gastritis in more than 53%
      cases, an inflammation of duodenal bulbus in 34% and H.pylori infection in 50%
      cases.

PMID- 9139781
TI  - [Early results of treating Helicobacter pylori infections in patients with
      gastric ulcer and gastritis].
AB  - In the present study, the effectiveness of a triple therapy for eradication of
      Helicobacter pylori was evaluated. Therapy consisted of 120 mg tripotassium
      dicitrato bismuthate q.d.s. for four weeks, 500 mg amoxycillin q.d.s. and 500 mg
      metronidazole t.d.s. for two weeks. In 77 Helicobacter pylori-positive patients
      with duodenal ulcers (n = 32), gastritis (n = 18) and after gastric resection (n
      = 7), rapid urease-based test, culture, histology and serology were used to
      confirm the eradication, or relapse. The overall eradication rate was 75.3%,
      ulcers were healed in 82.1% and an improvement of the endoscopic gastritis was
      observed in 75.3% of the patients. The eradication rates were not statistically
      different among the subgroups. 1-3 months after the treatment IgG titres had
      fallen by 25% and over in 67.5% of the patients irrespective of the success of
      bacterial eradication. Side effects, particularly diarrhoea and nausea, were
      common (53.2%) but mild. Only 6.5% of the patients' had to discontinue the
      treatment because side effects became intolerable.

PMID- 9139782
TI  - [The pancreolaurinic test in patients with chronic pancreatitis and in patients
      with perforated acute pancreatitis].
AB  - They presented a valuation of exocrine pancreatic function using pancreolaurinic
      test in 15 patients with chronic pancreatitis and in 34 patients after acute
      pancreatitis. In all patients with chronic pancreatitis they noted an
      insufficiency of exocrine pancreatic function with association of disorders of
      tolerance for carbohydrates during a year after a Puestow's operation. They noted
      a handicap of exocrine pancreatic function in 42% patients just after acute
      pancreatitis, in 18% patients a year acute pancreatitis and in 26% patients after
      2-6 years from illness with association of disorders of tolerance for
      carbohydrates.

PMID- 9139783
TI  - [Exocrine pancreatic function and gastric mucosa and duodenal mucosa in patients
      with chronic kidney failure].
AB  - Uraemic pancreatopathy is frequently observed in patients with chronic renal
      failure. The aim of the study was to assess some parameters of exocrine
      pancreatic function in uraemic patients maintained on intermittent haemodialyses.
      Elevated serum amylase activity was found in these patients. The most significant
      finding was the low bicarbonate output in duodenal content after secretin
      cerulein stimuli, comparable with that obtained in patients with chronic
      pancreatitis. It indicates pancreatic exocrine defect in uraemic patients. A fall
      in protein output and lower amylase activity in duodenal content was also
      observed in haemodialyzed patients after stimulation. Low basal acid output (BAO)
      and enhanced maximal (MAO) and peak (PAO) acid outputs were found in uraemic
      patients after pentagastrin stimulation. Gastritis and duodenitis were frequently
      diagnosed in endoscopic and histopathological examinations in these patients. In
      patients with chronic renal failure even without clinical signs of pancreatic,
      laboratory findings of exocrine pancreatic abnormalities are reported. It may be
      the cause of uraemic pancreatopathy.

PMID- 9139784
TI  - [Prognosis in acute viral hepatitis B in children].
AB  - Epidemiological evaluations indicate an increase of acute viral hepatitis B in
      children. In this study authors performed an analysis of disease prognosis in
      retrospective trial in children hospitalized in the Pediatric Department of
      Infectious Diseases from 1983 to 1993 because of acute viral hepatitis B. It was
      documented that a risk of persistent hepatitis B may be related to the age of
      patients with acute viral hepatitis B in the past. In 64% of analyzed patients
      below 1 year old and in 20% over 6 years-persistent hepatitis was diagnosed,
      especially in male subjects.

PMID- 9139785
TI  - [Coexistence of some diseases and analysis of death causes based on autopsy
      examinations carried out in liver cirrhosis patients based on autopsy
      observations in 1976-1990].
AB  - The 19,094 autopsy examinations carried out between 1976-1990 revealed 698
      (3.65%) case of cirrhosis, of which 64.6% were men. During the last 5 years the
      percentage of coexistance of hepatoma (hepatocellular carcinoma) with cirrhosis
      was higher 5-year periods (5.8%; 5.4%). Moreover, the same changing interrelation
      was observed for other malignancies and cirrhosis-higher (15%) in the last period
      than in the proceeding years (11.1%; 11.3%). The severity of atherosclerotic
      changes and coexistance of peptic ulcers, gall bladder disease and productive
      pulmonary tuberculosis in cirrhotic patients were also assessed. Finally the
      direct causes of these patients' death were discussed.

PMID- 9139786
TI  - [Changes in secretion of cholecystokinin after cholecystectomy and the effect of
      these changes on biliary reflux and the state of the gastric mucosa].
AB  - Cholecystokinin's role in regulations of gallbladder and gastric function was
      well documented. After cholecystectomy a secretion of cholecystokinin may be
      changed and observed symptoms are able to create a new clinical picture including
      biliary gastric reflux. In the study was noticed that in 12 patients after
      cholecystectomy the cholecystokinin secretion was increased in comparison to the
      period before operation. Observed increased levels of the enzyme were not in
      connection with biliary gastric reflux.

PMID- 9139787
TI  - [Diagnostic and therapeutic problems in ulcerative colitis].
AB  - This article discusses two specific atypical cases of ulcerative colitis
      encountered in the Inpatient Internal Diseases Department at Czerniakowski
      Hospital, Warsaw, Poland. Ulcerative colitis usually manifests itself primarily
      in the gastrointestinal tract, what made these cases exceptional was the
      involvement of multiple organs which complicated the diagnosis. The first of this
      cases presented a rare combination of symptoms of ulcerative colitis,
      cytomegalovirus infection, and polychondritis. The second case involved a patient
      initially diagnosed with myelogenous leukemia, however subsequent investigation
      revealed a sever case of ulcerative colitis and not leukemia as originally
      suspected.

PMID- 9139788
TI  - [Sigmoid-vesical fistula as a consequence of sigmoid tumor].
AB  - Because of unusual rarity of neoplastic sigmoid-vesical fistula in young patients
      the case of 43 years old woman, in whom the fistula was the consequence of
      sigmoid adenocarcinoma infiltration of urinary bladder, was presented. The
      patient was treated radically by resection of the sigmoid and partial resection
      of the urinary bladder within healthy tissue. After operation the patient was
      exposed to radiotherapy, after which chemotherapy followed (6 courses of 5-day
      chemotherapy with fluorouracil and calcium folinate). 18 months after operation,
      16 months after radiotherapy and 14 after chemotherapy patient's general
      condition was good and control laboratory tests did not indicate the relapse of
      the neoplasm.

PMID- 9139789
TI  - [Multiorgan trauma complicated by purulent processes and occlusion of the
      digestive tract].
AB  - Authors presented a case of multiorgan trauma complicated, during a treatment by
      purulent course and occlusion of digestive tract. They punctuate an important
      rate of intensive care and postoperative care, which enabled a diagnose of early
      dangerous complications and effective treatment.

PMID- 9139790
TI  - [Primary distal renal tubular acidosis coexisting with malabsorption syndrome].
AB  - The authors present the case of 54-old man primary tubular acidosis coexisting
      with malabsorption syndrome. Deviation were: extension of QT interval, low level
      of potassium and calcium in the blood, perturbations of calcium metabolism and
      high level of PTH. Glucose, lactose and iron absorption curves were flat. The
      final diagnosis was given as a result of analysis of findings and literature. The
      patient underwent the vitamin D3, calcium and potassium preparations,
      hydrochlorotiazyd treatment. Megaloblastic anaemia was treated with vitamin B12
      and folic acid. Such therapy gave considerable improvement in patient's general
      condition and normalisation of lab tests results. The authors try explain the
      etiopathogenesis of bones changes and high level of parathormone. They assume the
      attitude towards methods of therapy and necessary medicaments doses. Relationship
      between described syndromes remains inextricable. Roentgen image of ileum which
      suggests occlusion is still unexplainable. Described case seemed to be very
      interesting considering rarity of primary tubular acidosis and its coexistence
      with malabsorption syndrome.

PMID- 9139791
TI  - [A case of Wilson's disease with an atypical clinical course].
AB  - The case of atypical course of Wilson's disease in a 31 years old woman was
      reported. Basing on its clinical presentation it was classified as a liver form.
      The laboratory criteria necessary for the diagnosis of this disease are as
      follows: increase of cooper concentration in liver tissue (above 500 micrograms
      copper per gram dry substance), defect of copper incorporation into ceruloplasmin
      in 24 hours copper excretion test in urine (above mumol/24 h). In this report the
      main principles of pharmacotherapy were summarized, with particular stress on the
      necessity throughout the patient's life.

PMID- 9139792
TI  - [Neoplasms and congenital abnormalities of extrahepatic bile ducts].
AB  - Some problems of association of gallbladder carcinoma and congenital
      abnormalities of extrahepatic bile ducts are discussed in diagnostic and
      therapeutic aspects. Presented facts have been not quite clear to explain
      carcinogenesis of extrahepatic bile ducts.

PMID- 9139793
TI  - [Treatment of hypercholesterolemia--the other side of the coin].
AB  - Over 30 years of follow up from the Framingham Study an association between serum
      cholesterol concentration and ischemic heart disease is still analyzed. Critical
      evaluation shows that a decrease of cholesterol concentration cause a decrease of
      ischemic heart disease prevalence.

PMID- 9139794
TI  - [Science priority, medical paternalism or participation in medical practice].
AB  - During a last decade alternative methods in medicine were observed. A resin of
      this situation is a crisis of believe in scientific medicine.

PMID- 9139795
TI  - [Postoperative wound infections in patients from the surgical department].
AB  - The microbiological evaluation of postoperative wound infections is discussed in
      aspects of risk factors. In analyzed material Enterobacteriaceae and
      Staphylococci coagulase-positive were detected as a main cause of infection.

PMID- 9139796
TI  - Induction of promiscuous G protein coupling of the follicle-stimulating hormone
      (FSH) receptor: a novel mechanism for transducing pleiotropic actions of FSH
      isoforms.
AB  - Under physiological conditions, FSH is secreted into the circulation as a complex
      mixture of several isoforms that vary in the degree of glycosylation. Although it
      is well established that the glycosylation of FSH is important for the serum half
      life of the hormone and coupling of the receptor to adenylate cyclase, little is
      known concerning how physiologically occurring glycosylation patterns of this
      hormone affect receptor signaling. In this study, we have examined the biological
      activity of deglycosylated human FSH (DeGly-phFSH), recombinant mammalian
      expressed hFSH (CHO-hFSH), and insect cell-expressed hFSH (BV-hFSH, alternatively
      glycosylated) as compared with that of purified human pituitary FSH (phFSH) using
      a Chinese hamster ovarian cell line stably expressing the hFSH receptor (3D2
      cells). Differentially glycosylated forms of FSH did not bind to the FSH receptor
      in the same manner as phFSH. Although all hormones showed similar potency in
      competing for [125I]phFSH binding to the hFSH receptor, competition curves for
      deglycosylated and insect cell-produced FSH were steeper. Similarly,
      glycosylation of FSH had a profound effect on bioactivity of the hormone.
      Purified hFSH produced a sigmoidal dose-dependent stimulation in cAMP production,
      whereas DeGly-phFSH and BV-hFSH induced biphasic (bell-shaped) dose-response
      curves. BV-hFSH also elicited biphasic effects on steroidogenesis in primary
      cultures of rat granulosa cells. The cellular response to BV-hFSH was dependent
      on the degree of receptor-transducer activation. BV-hFSH bioactivity was strictly
      inhibitory when combined with the ED80 of phFSH. Lower concentrations of phFSH
      resulted in a gradual shift from inhibition to a biphasic activity in the
      presence of the ED20 of phFSH. Biphasic responses to BV-hFSH were attributed to
      activation of different G protein subtypes, since treatment of 3D2 cells with
      cholera toxin or pertussis toxin differentially blocked the two phases of BV-hFSH
      bioactivity. These data suggest that alternative glycosylation of FSH leads to a
      functionally altered form of the hormone. Functionally different hormones appear
      to convey distinct signals that are transduced by the receptor-transduction
      system as either stimulatory or inhibitory intracellular events via promiscuous,
      glycosylation-dependent G protein coupling. Promiscuity in signaling of the FSH
      receptor, in turn, may represent a potentially novel mechanism for FSH action,
      whereby the gonad may respond in diverse ways to complex hormonal signals such as
      those presented by circulating FSH isoforms.

PMID- 9139797
TI  - Coupling specificity between somatostatin receptor sst2A and G proteins:
      isolation of the receptor-G protein complex with a receptor antibody.
AB  - Somatostatin initiates its actions via a family of seven-transmembrane domain
      receptors. Of the five somatostatin receptor genes cloned, sst2 exists as two
      splice variants with the sst2A isoform being predominantly expressed. This
      receptor is widely distributed in endocrine, exocrine, and neuronal cells, as
      well as in hormonally responsive tumors, and leads to inhibition of secretion,
      electrical excitability, and cell proliferation. To investigate the specificity
      of signal transduction by the sst2A receptor, we developed antibodies against two
      overlapping peptides located within the C terminus of the receptor protein:
      peptide 2C(SG), containing amino acids 334-348, and peptide 2C(ER), containing
      amino acids 339-359. Although antibodies to both peptides bound the inducing
      antigen with high affinity, only the antibodies against peptide 2C(ER)
      precipitated the receptor. The best antibody, R2-88, precipitated about 80% of
      the sst2A receptor-ligand complex solubilized from transfected CHO cells and was
      specific for the sst2A receptor isotype. Addition of GTPgammaS (10 microM) to the
      immunoprecipitated ligand-sst2A receptor complex markedly accelerated ligand
      dissociation, indicating that G proteins remained functionally associated with
      the receptor in the immunoprecipitate. Analysis of the G proteins coprecipitated
      with the sst2A receptor by immunoblotting with G protein antibodies showed that
      both G(alpha) and G(beta) subunits were bound to the hormone-receptor complex.
      Immunoprecipitation of the receptor was not affected by the presence of bound
      ligand. However, G protein subunits were coprecipitated only with the hormone
      occupied receptor. Thus, the unoccupied receptor has low affinity for G proteins,
      and hormone binding stabilizes the receptor-G protein complex. Use of subtype
      specific G protein antisera further showed that G alpha(i1), G alpha(i2), and G
      alpha(i3) were complexed with the sst2A receptor whereas Galpha(o), G alpha(z),
      and G alpha(q) were not. Together, these studies demonstrate that the sst2A
      receptor interacts selectively with G alpha(i) proteins in a hormone-dependent
      manner. The finding that this receptor couples to all three G alpha(i) subunits
      may help explain how somatostatin can regulate multiple signaling pathways.

PMID- 9139798
TI  - Luteinizing hormone/choriogonadotropin-dependent, cholera toxin-catalyzed
      adenosine 5'-diphosphate (ADP)-ribosylation of the long and short forms of Gs
      alpha and pertussis toxin-catalyzed ADP-ribosylation of Gi alpha*.
AB  - Although it is well established that activated LH/human (h) CG receptor
      stimulates adenylyl cyclase activity (via the heterotrimeric stimulatory guanine
      nucleotide-binding protein, Gs) and in some cells stimulates phospholipase C
      activity, there is no evidence for a direct physical interaction between the
      LH/CG receptor and Gs or any other G protein(s). We conducted studies using
      cholera toxin (CTX) and pertussis toxin (PTX) to determine which G alpha proteins
      were associated with the LH/CG receptor in ovarian follicular membranes. Since
      hormone-dependent, CTX-catalyzed ADP ribosylation (AR) constitutes evidence that
      a G alpha protein is specifically associated with a receptor, CTX-catalyzed AR of
      membrane proteins was examined both in the presence and absence of guanine
      nucleotides to determine which G proteins exhibit hCG-dependent labeling by
      [32P]NAD. Results demonstrated the time- and hCG-dependent AR of both a 45-kDa
      protein and a 48/50-kDa doublet as well as a 40-kDa protein that was also
      sensitive to AR by PTX in a time- and hCG-dependent manner. Using anti-G protein
      antisera to specifically immunoprecipitate photoaffinity-labeled G proteins, we
      were able to identify the 45- and 48/50 kDa proteins as the short and long forms
      of Gs alpha and the 40-kDa protein as Gi alpha. A monoclonal anti-hCG antibody
      immunoprecipitated the activated LH/CG receptor along with the long and short
      forms of Gs alpha and Gi. These results suggest that a portion of Gi along with
      the long and short forms of Gs alpha are associated physically with the LH/CG
      receptor in ovarian follicular membranes.

PMID- 9139799
TI  - The six N-linked carbohydrates of the lutropin/choriogonadotropin receptor are
      not absolutely required for correct folding, cell surface expression, hormone
      binding, or signal transduction.
AB  - Using two separate methods, we have determined that all six potential sites for N
      linked glycosylation on the rat lutropin/choriogonadotropin receptor (rLHR)
      contain carbohydrates. The functional roles of the carbohydrates were analyzed
      initially through the use of two nonglycosylated receptor mutants
      rLHR(N(77,152,173,269,277,291)Q) and rLHR(N(77,152,269,277,291)Q;T(175)A).
      Although Western blot analyses demonstrated both mutant receptors to be stably
      expressed, little or no hCG binding activity could be detected in detergent
      solubilized extracts of 293 cells expressing either nonglycosylated LHR mutant.
      Although this loss of hCG binding was concluded to be due to misfolding, it was
      unknown whether this misfolding was due to the absence of carbohydrates or to the
      multiple amino acid substitutions that had been introduced into the polypeptide.
      To differentiate between these possibilities, hCG binding assays were performed
      with nonglycosylated receptors obtained after tunicamycin treatment of cells
      expressing the wild-type rLHR. Even though these wild-type receptors were
      confirmed to be devoid of all N-linked carbohydrates by Western blots, they were
      found to bind hCG with a normal high affinity. In addition, tunicamycin-derived,
      nonglycosylated LHRs were present at the cell surface and exhibited a phenotype
      consistent with mature receptors due to their capability to mediate hCG
      stimulated cAMP production as well as bind oLH with high affinity. These results
      indicate that the loss of high affinity hormone binding by
      rLHR(N(77,152,173,269,277,291)Q) and rLHR(N(77,152,269,277,291)Q;T(175)A) is
      simply due to the collective amino acid substitutions rather than to the absence
      of carbohydrates. Therefore, N-linked carbohydrates are not absolutely required
      for the proper folding of the rLHR into a mature receptor capable of binding
      hormone and signaling. These results are in marked contrast to the follitropin
      receptor (FSHR), a very similar receptor which has been shown to strictly require
      N-linked carbohydrates for folding of the nascent protein.

PMID- 9139801
TI  - Glucocorticoid inhibition of fibroblast proliferation and regulation of the
      cyclin kinase inhibitor p21Cip1.
AB  - Glucocorticoids inhibit the proliferation of fibroblastic cells in vivo and in
      culture; however, the molecular mechanism that accounts for this effect has
      remained obscure. We have undertaken to elucidate the mechanism whereby
      glucocorticoids decrease the rate of proliferation of mouse L929 fibroblastic
      cells. Addition of dexamethasone to mid-log phase fibroblasts prolongs G1 phase.
      This increase in the G1 interval is associated with, and probably due to,
      inhibition of phosphorylation of the product of the Rb-1 tumor suppressor gene,
      pRb. Inhibition of pRb phosphorylation by cyclin D-dependent kinases can be
      demonstrated in vitro. Nevertheless, there is no detectable change in the
      expression of cyclin D1, cyclin D2, or cyclin D3. Cyclin-dependent kinase-4
      (Cdk4) and Cdk6 are not down-regulated in L929 cells after addition of
      glucocorticoids, and the abundance of cyclin D/Cdk4 complexes does not change.
      Inhibition of pRb kinase activity is associated with an increase in the abundance
      of one of the Cdk inhibitors, p21Cip1. The abundance of another cyclin kinase
      inhibitor, p27Kip1, remains constant. The amount of Cdk4 that is bound to p21Cip1
      increases rapidly after addition of dexamethasone, and the activity of Cdk4-pRb
      kinase decreases in parallel. These results indicate that glucocorticoid
      inhibition of fibroblast proliferation is due to induction of p21Cip1, which
      binds to and inactivates cyclinD/Cdk4 complexes. The abundance of p21 mRNA
      increases about 5-fold within 2 h after addition of dexamethasone. This effect
      does not obtain in L929 mutants that are null for the glucocorticoid receptor,
      and a variant that expresses the glucocorticoid receptor from a tetracycline
      repressible expression vector demonstrates induction of p21 mRNA only in the
      absence of tetracycline. Cycloheximide does not block induction of p21 mRNA, and
      dexamethasone has no detectable effect on the apparent rate of degradation of p21
      mRNA. Nuclear run-on transcription of the Cip1 gene increases within 2 h after
      addition of dexamethasone. This effect can be blocked by tetracycline-mediated
      repression of the glucocorticoid receptor.

PMID- 9139802
TI  - Estrogen receptor residues required for stereospecific ligand recognition and
      activation.
AB  - The mouse estrogen receptor (mER) has been shown to exhibit stereospecific
      binding of certain stilbene estrogen agonists. The region of the mER involved in
      the stereochemical recognition of ligands was further defined using a stilbene
      isomer, Indenestrol B (IB). The IB compound has a chiral carbon bearing an ethyl
      substituent, and the wild type uterine mER has been shown to bind the
      enantiomers, IB-S and IB-R, with similar affinity. The wild type mER expressed in
      yeast exhibited a very minor preference for IB-S in transactivation (1.5-fold
      lower half-maximal dose than IB-R). The IB enantiomers could then be used to
      determine whether stereochemically distinct compounds with similar
      transcriptional activity utilize different amino acids in AF-2 for
      transactivation. Mutant mERs with glycine substitutions at Met521, His528,
      Met532, and Val537 were expressed in yeast and measured for IB-S- and IB-R
      induced transactivation and ligand binding. The M532G mER showed a 124-fold and
      50-fold reduction in transactivation induced by IB-S and IB-R, respectively,
      without a corresponding change in their ligand-binding affinities. Therefore,
      Met532 is required for transactivation induced by both IB enantiomers but does
      not discriminate based on stereospecificity. In contrast, the H528G mER displayed
      a gross change in stereospecific ligand recognition as illustrated by a 110-fold
      reduction in transactivation by IB-S and only a 8.8-fold decrease in activity by
      IB-R. As a result, H528G mER displayed a switch in ligand preference such that IB
      R was now 8-fold more active than IB-S in transactivation. Therefore, His528
      appears largely involved in transactivation specifically induced by IB-S but has
      a minimal influence in IB-S ligand binding. The remaining mutant mERs displayed
      wild type ligand binding and transactivation properties for the IB enantiomers
      illustrating no stereospecific recognition. These results imply that individual
      IB enantiomers bind to the mER with similar affinity but utilize at least one
      different amino acid within the AF-2 domain for signal transduction. The binding
      of stereochemically distinct ligands may alter the tertiary structure of the mER
      and cause repositioning of the AF-2 region that mediates transcription of
      specific genes and/or affect the binding of receptor-associated proteins, such as
      coactivators, which could influence transcription.

PMID- 9139800
TI  - Novel accessory factor-binding site required for glucocorticoid regulation of the
      gamma-fibrinogen subunit gene from Xenopus laevis.
AB  - Glucocorticoids induce gene expression by binding to an intracellular receptor
      that interacts with genomic DNA and stimulates transcription of specific genes.
      The consensus DNA-binding site for the glucocorticoid receptor, called a
      glucocorticoid response element (GRE), is GGTACAnnnTGTTCT. In the classical
      model, binding of the receptor as a dimer to the two halves of the GRE is
      required for activation of transcription. For some glucocorticoid-regulated
      genes, additional DNA-binding proteins called accessory factors are necessary for
      hormonal responsiveness. We have identified a new factor required for
      glucocorticoid-induced expression of the gamma-fibrinogen subunit gene from the
      frog Xenopus laevis. Transfection of cloned DNA fragments into primary Xenopus
      hepatocytes showed that the DNA between 163 and 187 bp upstream of the
      transcription initiation site is essential for hormonal activation. A single
      complex forms when this small region of DNA is incubated in vitro with Xenopus
      liver nuclear proteins. The protein recognition site has been narrowed to
      AAGAGTTAA, a sequence not previously described as a transcription factor-binding
      site. We have named the protein(s) bound to this sequence Xenopus glucocorticoid
      receptor accessory factor (XGRAF). In addition to the XGRAF-binding site,
      glucocorticoid regulation of the gamma-fibrinogen gene requires at least three
      nearby GREs, each of which is a poor match to the consensus GRE. The position of
      the binding site for XGRAF overlaps the putative upstream half of the most
      important GRE. Models are presented to show possible ways that the novel
      accessory factor and the glucocorticoid receptor could act through closely
      juxtaposed sites on the DNA.

PMID- 9139803
TI  - Phosphatidylinositol 3-kinase is a requirement for insulin-like growth factor I
      induced differentiation, but not for mitogenesis, in fetal brown adipocytes.
AB  - In the present study we have examined the role of phosphatidylinositol 3-kinase
      (PI 3-kinase) in the insulin-like growth factor I (IGF-I)-signaling pathways
      involved in differentiation and in mitogenesis in fetal rat brown adipocytes.
      Activation of PI 3-kinase in response to IGF-I was markedly inhibited by two PI 3
      kinase inhibitors (wortmannin and LY294002) in a dose-dependent manner. IGF-I
      stimulated glucose uptake was also inhibited by both compounds. The expression of
      adipogenic-related genes such as fatty acid synthase, malic enzyme, glycerol 3
      phosphate dehydrogenase, and acetylcoenzyme A carboxylase induced by IGF-I was
      totally prevented in the presence of IGF-I and any of those inhibitors, resulting
      in a marked decrease of the cytoplasmic lipid content. Moreover, the expression
      of the thermogenic marker uncoupling protein induced by IGF-I was also down
      regulated in the presence of wortmannin/LY294002. IGF-I-induced adipogenic- and
      thermogenic-related gene expression was only partly inhibited by the p70S6k
      inhibitor rapamycin. In addition, pretreatment of brown adipocytes with either
      wortmannin or LY294002, but not with rapamycin, blocked protein kinase C zeta
      activation by IGF-I. In contrast, IGF-I-induced fetal brown adipocyte
      proliferation was PI 3-kinase-independent. Our results show for the first time an
      essential requirement of PI 3-kinase in the IGF-I-signaling pathways leading to
      fetal brown adipocyte differentiation, but not leading to mitogenesis. In
      addition, protein kinase C zeta seems to be a signaling molecule also involved in
      the IGF-I differentiation pathways downstream from PI 3-kinase.

PMID- 9139804
TI  - Role of Bag-1 in the survival and proliferation of the cytokine-dependent
      lymphocyte lines, Ba/F3 and Nb2.
AB  - The expression and function of the newly identified Bcl-2- and Raf-1- binding
      protein, Bag-1, during the cytokine-regulated growth of B and T cell lines was
      examined. Immunoblot analysis of lysates from the interleukin-3 (IL-3)-dependent
      B cell line Ba/F3, and the PRL-dependent T cell line Nb2, revealed that
      variations in Bag-1 levels paralleled alterations in cellular proliferation,
      viability, and apoptosis induced by the presence or absence of growth factor. To
      test whether up-regulation of Bag-1 levels altered cellular survival and
      proliferation, Ba/F3 cells were transfected with a Bag-1 expression construct.
      The overexpression of Bag-1 in transfected Ba/F3 cells induced an IL-3
      independent state. Such transfectants demonstrated sustained viability and
      proliferation, with minimal apoptosis, in the complete absence of exogenous IL-3.
      Bag-1 expression was also compared in glucocorticoid-sensitive Nb2 cells and a
      PRL-independent, glucocorticoid-resistant subline, SFJCD1, during culture of
      these lines in dexamethasone (Dex). Bag-1 levels were profoundly decreased by the
      addition of Dex to Nb2 cells, precedent to the onset of apoptotic cell death. In
      contrast, Dex treatment or PRL withdrawal had no effect on levels of Bag-1 within
      the SFJCD1 line. These findings establish that the overexpression of Bag-1 in the
      appropriate cellular context promotes cellular survival and growth, events that
      may result from the juxtaposition of this protein with mitogenic and
      antiapoptotic signaling pathways.

PMID- 9139805
TI  - L-type calcium channels in insulin-secreting cells: biochemical characterization
      and phosphorylation in RINm5F cells.
AB  - Opening of dihydropyridine-sensitive voltage-dependent L-type Ca2+-channels
      (LTCCs) represents the final common pathway for insulin secretion in pancreatic
      beta-cells and related cell lines. In insulin-secreting cells their exact subunit
      composition is unknown. We therefore investigated the subunit structure of (+)
      [3H]isradipine-labeled LTCCs in insulin-secreting RINm5F cells. Using subunit
      specific antibodies we demonstrate that alpha1C subunits (199 kDa, short form)
      contribute only a minor portion of the total alpha1 immunoreactivity in membranes
      and partially purified Ca2+-channel preparations. However, alpha1C forms a major
      constituent of (+)-[3H]isradipine-labeled LTCCs as 54% of solubilized (+)
      [3H]isradipine-binding activity was specifically immunoprecipitated by alpha1C
      antibodies. Phosphorylation of immunopurified alpha1C with cAMP-dependent protein
      kinase revealed the existence of an additional 240-kDa species (long form), that
      remained undetected in Western blots. Fifty seven percent of labeled LTCCs were
      immunoprecipitated by an anti-beta-antibody directed against all known beta
      subunits. Isoform-specific antibodies revealed that these mainly corresponded to
      beta1b- and beta3-subunits. We found beta2- and beta4-subunits to be major
      constituents of cardiac and brain L-type channels, respectively, but not part of
      L-type channels in RINm5F cells. We conclude that alpha1C is a major constituent
      of dihydropyridine-labeled LTCCs in RINm5F cells, its long form serving as a
      substrate for cAMP-dependent protein kinase. beta1b- and beta3-Subunits were also
      found to associate with L-type channels in these cells. These isoforms may
      therefore represent biochemical targets for the modulation of LTCC activity in
      RINm5F cells.

PMID- 9139806
TI  - Induction of neuropeptide Y gene expression in the dorsal medial hypothalamic
      nucleus in two models of the agouti obesity syndrome.
AB  - Dominant mutations at the agouti locus induce several phenotypic changes in the
      mouse including yellow pigmentation (phaeomelanization) of the coat and adult
      onset obesity. Nonpigmentary phenotypic changes associated with the agouti locus
      are due to ectopic expression of the agouti-signaling protein (ASP), and the
      pheomelanizing effects on coat color are due to ASP antagonism of alpha-MSH
      binding to the melanocyte MC1 receptor. Recently it has been demonstrated that
      pharmacological antagonism of hypothalamic melanocortin receptors or genetic
      deletion of the melanocortin 4 receptor (MC4-R) recapitulates aspects of the
      agouti obesity syndrome, thus establishing that chronic disruption of central
      melanocortinergic signaling is the cause of agouti-induced obesity. To learn more
      about potential downstream effectors involved in these melanocortinergic obesity
      syndromes, we have examined expression of the orexigenic peptides galanin and
      neuropeptide Y (NPY), as well as the anorexigenic POMC in lethal yellow (A(y)),
      MC4-R knockout (MC4-RKO), and leptin-deficient (ob/ob) mice. No significant
      changes in galanin or POMC gene expression were seen in any of the obese models.
      In situ hybridizations using an antisense NPY probe demonstrated that in obese
      A(y) mice, arcuate nucleus NPY mRNA levels were equivalent to that of their
      C57BL/6J littermates. However, NPY was expressed at high levels in a new site,
      the dorsal medial hypothalamic nucleus (DMH). Expression of NPY in the DMH was
      also seen in obese MC4-RKO homozygous (-/-) mice, but not in lean heterozygous
      (+/-) or wild type (+/+) control mice. This identifies the DMH as a brain region
      that is functionally altered by the disruption of melanocortinergic signaling and
      suggests that this nucleus, possibly via elevated NPY expression, may have an
      etiological role in the melanocortinergic obesity syndrome.

PMID- 9139808
TI  - Spaceflight monkey's death 'raises new safety issues'.

PMID- 9139809
TI  - CJD link prompts ban on brain tissue use.

PMID- 9139807
TI  - Angiotensin II and potassium regulate human CYP11B2 transcription through common
      cis-elements.
AB  - Aldosterone synthase is a mitochondrial enzyme that catalyzes the conversion of
      11-deoxycorticosterone to the potent mineralocorticoid aldosterone. The gene
      encoding aldosterone synthase, CYP11B2, is expressed in the zona glomerulosa of
      the adrenal cortex. Although the major physiological regulators of aldosterone
      production are angiotensin II (ANG II) and potassium (K+), the mechanisms by
      which these compounds regulate CYP11B2 transcription are unknown. Therefore we
      analyzed the human CYP11B2 5'-flanking region using a transient transfection
      expression system in the H295R human adrenocortical cell line. ANG II and K+
      increased expression of a luciferase reporter construct containing 2015 bp of
      human CYP11B2 5'-flanking DNA. This response was mimicked by treatment with the
      calcium channel activator BAYK8644, whereas activation of the protein kinase C
      pathway with 12-o-tetradecanoylphorbol-13-acetate had no effect. Reporter gene
      activity was also increased after activation of cAMP-dependent pathways by
      (Bu)2cAMP. Deletion, mutation, and deoxyribonuclease I footprinting analyses of
      the CYP11B2 5'-flanking region identified two distinct elements at positions -71/
      64 (TGACGTGA) and -129/-114 (CTCCAGCCTTGACCTT) that were both required for full
      basal reporter gene activity and for maximal induction by either cAMP or calcium
      signaling pathways. The -71/-64 element, which resembles a consensus cAMP
      response element (CRE), bound CRE-binding proteins from H295R cell nuclear
      extracts as determined by electrophoretic mobility shift analysis. Analysis of
      the -129/-114 element using electrophoretic mobility shift analysis demonstrated
      binding of the orphan nuclear receptors steroidogenic factor 1 and chicken
      ovalbumin upstream promoter transcription factor. These data demonstrate that ANG
      II, K+, and cAMP-signaling pathways utilize the same SF-1 and CRE-like cis
      elements to regulate human CYP11B2 expression.

PMID- 9139810
TI  - Structural biology gets UK funding boost.

PMID- 9139812
TI  - Gene researchers promised relief from regulatory burden.

PMID- 9139811
TI  - Korea leaps before it looks over gene therapy guidelines.

PMID- 9139813
TI  - Montagnier to set up an AIDS research centre in New York.

PMID- 9139814
TI  - Are patents and research compatible?

PMID- 9139815
TI  - Transcriptional control. Sinful repression.

PMID- 9139816
TI  - Protein transport. Greasing the Golgi budding machine.

PMID- 9139817
TI  - Evolutionary biology. The ancestry of segmentation.

PMID- 9139818
TI  - Colloid chemistry. Liposomes within liposomes.

PMID- 9139819
TI  - Obesity. Some heat but not enough light.

PMID- 9139820
TI  - A complex containing N-CoR, mSin3 and histone deacetylase mediates
      transcriptional repression.
AB  - Transcriptional repression by nuclear receptors has been correlated to binding of
      the putative co-repressor, N-CoR. A complex has been identified that contains N
      CoR, the Mad presumptive co-repressor mSin3, and the histone deacetylase mRPD3,
      and which is required for both nuclear receptor- and Mad-dependent repression,
      but not for repression by transcription factors of the ets-domain family. These
      data predict that the ligand-induced switch of heterodimeric nuclear receptors
      from repressor to activator functions involves the exchange of complexes
      containing histone deacetylases with those that have histone acetylase activity.

PMID- 9139821
TI  - Role for N-CoR and histone deacetylase in Sin3-mediated transcriptional
      repression.
AB  - Normal mammalian growth and development are highly dependent on the regulation of
      the expression and activity of the Myc family of transcription factors. Mxi1
      mediated inhibition of Myc activities requires interaction with mammalian Sin3A
      or Sin3B proteins, which have been purported to act as scaffolds for additional
      co-repressor factors. The identification of two such Sin3-associated factors, the
      nuclear receptor co-repressor (N-CoR) and histone deacetylase (HD1), provides a
      basis for Mxi1/Sin3-induced transcriptional repression and tumour suppression.

PMID- 9139822
TI  - Encapsulation of bilayer vesicles by self-assembly.
AB  - Vesicles of lipid bilayers have been investigated as drug-delivery vehicles for
      almost 20 years. The vesicles' interior space is separated from the surrounding
      solution because small molecules have only limited permeability through the
      bilayer. Single-walled (unilamellar) vesicles are made by a variety of non
      equilibrium techniques, including mechanical disruption of lamellar phases by
      sonication or extrusion through filters, or chemical disruption by detergent
      dialysis or solvent removal. These techniques do not, however, allow the
      encapsulation of a specific volume, nor can they be used to encapsulate other
      vesicles. Here we show that molecular-recognition processes mediated by
      lipophilic receptors and substrates (here the biotin-streptavidin complex) can be
      used to produce a multicompartmental aggregate of tethered vesicles encapsulated
      within a large bilayer vesicle. We call these encapsulated aggregates vesosomes.
      Encapsulation is achieved by unrolling bilayers from cochleate cylinderss which
      are tethered to the aggregate by biotin-streptavidin coupling. These
      compartmentalized vesosomes could provide vehicles for multicomponent or
      multifunctional drug delivery; in particular, the encapsulating membrane could
      significantly modify permeation properties, or could be used to enhance the
      biocompatibility of the system.

PMID- 9139823
TI  - Contrast dependence of contextual effects in primate visual cortex.
AB  - The responses of neurons in the visual cortex to stimuli presented within their
      receptive fields can be markedly modulated by stimuli presented in surrounding
      regions that do not themselves evoke responses. This modulation depends on the
      relative orientation and direction of motion of the centre and surround stimuli,
      and it has been suggested that local cortical circuits linking cells with similar
      stimulus selectivities underlie these phenomena. However, the functional
      relevance and nature of these integrative processes remain unclear. Here we
      investigate how such integration depends on the relative activity levels of
      neurons at different points across the cortex by varying the relative contrast of
      stimuli over the receptive field and surrounding regions. We show that simply
      altering the balance of the excitation driving centre and surround regions can
      dramatically change the sign and stimulus selectivity of these contextual
      effects. Thus, the way that single neurons integrate information across the
      visual field depends not only on the precise form of stimuli at different
      locations, but also crucially on their relative contrasts. We suggest that these
      effects reflect a complex gain-control mechanism that regulates cortical neuron
      responsiveness, which permits dynamic modification of response properties of
      cortical neurons.

PMID- 9139824
TI  - Neuronal release of soluble nucleotidases and their role in neurotransmitter
      inactivation.
AB  - Efficient control of synaptic transmission requires a rapid mechanism for
      terminating the actions of neurotransmitters. For amino acids and monoamines,
      this is achieved by their uptake into the cell by specific high-affinity
      transporters; acetylcholine is first broken down in the extracellular space and
      then choline is taken up by the cell. Because ATP is hydrolysed to adenosine by
      membrane-bound enzymes (ectonucleotidases) that are present in most tissues, it
      has been assumed that these enzymes terminate the neurotransmitter actions of ATP
      in the brain and in the periphery. We show here, however, that stimulation of
      sympathetic nerves innervating the guinea-pig vas deferens releases not only
      neuronal ATP, but also soluble nucleotidases that break down this ATP to
      adenosine, indicating that inactivation of ATP is increased by nerve activity.
      This release of specific nucleotidases together with ATP represents a new
      mechanism for terminating the actions of a neurotransmitter.

PMID- 9139825
TI  - Connexin 26 mutations in hereditary non-syndromic sensorineural deafness.
AB  - Severe deafness or hearing impairment is the most prevalent inherited sensory
      disorder, affecting about 1 in 1,000 children. Most deafness results from
      peripheral auditory defects that occur as a consequence of either conductive
      (outer or middle ear) or sensorineuronal (cochlea) abnormalities. Although a
      number of mutant genes have been identified that are responsible for syndromic
      (multiple phenotypic disease) deafness such as Waardenburg syndrome and Usher 1B
      syndrome, little is known about the genetic basis of non-syndromic (single
      phenotypic disease) deafness. Here we study a pedigree containing cases of
      autosomal dominant deafness and have identified a mutation in the gene encoding
      the gap-junction protein connexin 26 (Cx26) that segregates with the profound
      deafness in the family. Cx26 mutations resulting in premature stop codons were
      also found in three autosomal recessive non-syndromic sensorineuronal deafness
      pedigrees, genetically linked to chromosome 13q11-12 (DFNB1), where the Cx26 gene
      is localized. Immunohistochemical staining of human cochlear cells for Cx26
      demonstrated high levels of expression. To our knowledge, this is the first non
      syndromic sensorineural autosomal deafness susceptibility gene to be identified,
      which implicates Cx26 as an important component of the human cochlea.

PMID- 9139826
TI  - Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member.
AB  - The transforming growth factor-beta (TGF-beta) superfamily encompasses a large
      group of growth and differentiation factors playing important roles in regulating
      embryonic development and in maintaining tissue homeostasis in adult animals.
      Using degenerate polymerase chain reaction, we have identified a new murine TGF
      beta family member, growth/differentiation factor-8 (GDF-8), which is expressed
      specifically in developing and adult skeletal muscle. During early stages of
      embryogenesis, GDF-8 expression is restricted to the myotome compartment of
      developing somites. At later stages and in adult animals, GDF-8 is expressed in
      many different muscles throughout the body. To determine the biological function
      of GDF-8, we disrupted the GDF-8 gene by gene targeting in mice. GDF-8 null
      animals are significantly larger than wild-type animals and show a large and
      widespread increase in skeletal muscle mass. Individual muscles of mutant animals
      weigh 2-3 times more than those of wild-type animals, and the increase in mass
      appears to result from a combination of muscle cell hyperplasia and hypertrophy.
      These results suggest that GDF-8 functions specifically as a negative regulator
      of skeletal muscle growth.

PMID- 9139827
TI  - Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese.
AB  - The mitochondrial uncoupling protein (UCP) in the mitochondrial inner membrane of
      mammalian brown adipose tissue generates heat by uncoupling oxidative
      phosphorylation. This process protects against cold and regulates energy balance.
      Manipulation of thermogenesis could be an effective strategy against obesity.
      Here we determine the role of UCP in the regulation of body mass by targeted
      inactivation of the gene encoding it. We find that UCP-deficient mice consume
      less oxygen after treatment with a beta3-adrenergic-receptor agonist and that
      they are sensitive to cold, indicating that their thermoregulation is defective.
      However, this deficiency caused neither hyperphagia nor obesity in mice fed on
      either a standard or a high-fat diet. We propose that the loss of UCP may be
      compensated by UCP2, a newly discovered homologue of UCP; this gene is
      ubiquitously expressed and is induced in the brown fat of UCP-deficient mice.

PMID- 9139828
TI  - Thermoregulatory and metabolic phenotypes of mice lacking noradrenaline and
      adrenaline.
AB  - Adrenaline and noradrenaline, the main effectors of the sympathetic nervous
      system and adrenal medulla, respectively, are thought to control adiposity and
      energy balance through several mechanisms. They promote catabolism of
      triglycerides and glycogen, stimulate food intake when injected into the central
      nervous system, activate thermogenesis in brown adipose tissue, and regulate heat
      loss through modulation of peripheral vasoconstriction and piloerection.
      Thermogenesis in brown adipose tissue occurs in response to cold and overeating
      (diet induced), and there is an inverse relationship between diet-induced
      thermogenesis and obesity both in humans and in animal models. As a potential
      model for obesity, we generated mice that cannot synthesize noradrenaline or
      adrenaline by inactivating the gene that encodes dopamine beta-hydroxylase. These
      mice are cold intolerant because they have impaired peripheral vasoconstriction
      and are unable to induce thermogenesis in brown adipose tissue through uncoupling
      protein (UCP1). The mutants have increased food intake but do not become obese
      because their basal metabolic rate is also elevated. The unexpected increase in
      basal metabolic rate is not due to hyperthyroidism, compensation by the widely
      expressed uncoupling protein UCP2, or shivering.

PMID- 9139829
TI  - Hox9 genes and vertebrate limb specification.
AB  - Development of paired appendages at appropriate levels along the primary body
      axis is a hallmark of the body plan of jawed vertebrates. Hox genes are good
      candidates for encoding position in lateral plate mesoderm along the body axis
      and thus for determining where limbs are formed. Local application of fibroblast
      growth factors (FGFs) to the anterior prospective flank of a chick embryo induces
      development of an ectopic wing, and FGF applied to posterior flank induces an
      ectopic leg. If particular combinations of Hox gene expression determine where
      wings and legs develop, then formation of additional limbs from flank should
      involve changes in Hox gene expression that reflect the type of limb induced.
      Here we show that the same population of flank cells can be induced to form
      either a wing or a leg, and that induction of these ectopic limbs is accompanied
      by specific changes in expression of three Hox genes in lateral plate mesoderm.
      This then reproduces, in the flank, expression patterns found at normal limb
      levels. Hox gene expression is reprogrammed in lateral plate mesoderm, but is
      unaffected in paraxial mesoderm. Independent regulation of Hox gene expression in
      lateral plate mesoderm may have been a key step in the evolution of paired
      appendages.

PMID- 9139831
TI  - Differential localization of transforming growth factor-beta isoforms in human
      gastric mucosa and overexpression in gastric carcinoma.
AB  - Transforming growth factor beta (TGF-beta) isoforms comprise a family of
      multifunctional polypeptide growth factors that either inhibit or stimulate cell
      proliferation. We examined TGF-beta expression in normal human gastric mucosa and
      carcinoma. The distribution and expression of TGF-beta isoforms in 4 normal
      mucosa samples from organ donors, in 12 normal mucosa samples adjacent to gastric
      cancer and in 12 gastric carcinomas were examined using immunohistochemistry and
      Northern blot analysis. Because TGF-beta s regulate collagen expression, collagen
      type I alpha1 mRNA amounts were also examined. Immunohistochemical analysis of
      normal human gastric tissue samples indicated that TGF-beta1 localized
      principally in parietal cells but also in some surface mucus cells, TGF-beta2 was
      present exclusively in chief cells and TGF-beta3 was present in parietal, chief
      and mucus cells. In the gastric cancers, strong colocalization of TGF-beta1, 
      beta2 and -beta3 was evident in the cancer cells. Northern blot analysis
      indicated that, compared to normal gastric tissue, gastric cancers showed a 4.8-
      and 6-fold increase in mRNA amounts encoding TGF-beta1 and TGF-beta3,
      respectively. In contrast, TGF-beta2 mRNA amounts were comparable in both groups.
      Northern blot analysis showed a 10-fold increase in human collagen type I alpha1
      mRNA amounts compared to normal gastric tissue. These findings imply a role
      forTGF-beta s in normal human gastric mucosa function, and raise the possibility
      that the aberrant colocalization and overexpression of all 3 TGF-beta isoforms in
      human gastric cancer cells in vivo may contribute to the pathobiology of gastric
      carcinoma.

PMID- 9139830
TI  - Essential role for diacylglycerol in protein transport from the yeast Golgi
      complex.
AB  - Yeast phosphatidylinositol transfer protein (Sec14p) is required for the
      production of secretory vesicles from the Golgi. This requirement can be relieved
      by inactivation of the cytosine 5'-diphosphate (CDP)-choline pathway for
      phosphatidylcholine biosynthesis, indicating that Sec14p is an essential
      component of a regulatory pathway linking phospholipid metabolism with vesicle
      trafficking (the Sec14p pathway). Sac1p (refs 7 and 8) is an integral membrane
      protein related to inositol-5-phosphatases such as synaptojanin, a protein found
      in rat brain. Here we show that defects in Sac1p also relieve the requirement for
      Sec14p by altering phospholipid metabolism so as to expand the pool of
      diacylglycerol (DAG) in the Golgi. Moreover, although short-chain DAG improves
      secretory function in strains with a temperature-sensitive Sec14p, expression of
      diacylglycerol kinase from Escherichia coli further impairs it. The essential
      function of Sec14p may therefore be to maintain a sufficient pool of DAG in the
      Golgi to support the production of secretory vesicles.

PMID- 9139832
TI  - Association of the Epstein-Barr virus with Hodgkin's disease in Southern Israel.
AB  - Epstein-Barr virus (EBV) has been frequently documented in the putative
      neoplastic Hodgkin-Reed-Sternberg (HRS) cells, in lymph nodes from patients with
      Hodgkin's disease (HD). This association varies in different geographic areas and
      between industrialized and developing countries, as does the epidemiological
      pattern of the disease. In the present study of 106 cases of HD from the Soroka
      Medical Center in Beer-Sheva, which serves as the only hospital for most of the
      southern part of Israel, we found an association with EBV expression in only 30%
      of the patients; 45% of mixed cellularity (MC) cases compared with 21% of nodular
      sclerosis (NS) cases were positive for EBV. The number of patients in the 0-14
      year-old age group was limited; however, 8 of these II children were EBV
      positive. This low association rate of HD with the presence of EBV sequences is
      probably related to the small number of children in our series. A low proportion
      of EBV-associated disease in older adults may be contributory. Other factors may
      be involved.

PMID- 9139833
TI  - Immunoselection in vivo: independent loss of MHC class I and melanocyte
      differentiation antigen expression in metastatic melanoma.
AB  - Peptides derived from melanocyte differentiation antigens have been identified as
      targets for MHC class I-restricted cytolytic T lymphocytes (CTLs) in human
      melanoma Regression of antigen-expressing tumors as well as selection of antigen
      loss variants in the presence of antigen-specific CTLs have previously been
      reported. In the present study, we determined the expression of the melanocyte
      differentiation antigens Melan A/MART-1 and tyrosinase by mRNA analysis and by
      immunohistochemical staining with the monoclonal antibodies (MAbs) A103 and T311.
      Co-expression of Melan A/MART-1 and tyrosinase was detected by both methods in
      18/20 melanomas tested. However, immunohistochemistry provided additional
      information on intensity and microheterogeneity of antigen expression that cannot
      be detected by mRNA analysis as a molecular basis for the escape from CTL
      recognition of antigen-negative tumor cells. Comparative analysis of repeated
      biopsies of metastatic lesions in 5 HLA-A2+ patients showed a gradual loss of
      Melan A/MART-1 expression in 4/5 and of tyrosinase in 2/5 samples in association
      with tumor progression. However, 3 of these patients had growing antigen-positive
      tumors in the presence of antigen-specific CTLs. This led us to assess the
      expression of MHC class I, the essential restriction element for CTL recognition,
      and of HLA-A2. We found an unexpectedly high frequency of MHC class I-negative
      tumors (9/20). Loss of MHC class I expression was detected in 3/5 progressive
      tumors and isolated loss of HLA-A2 in 1/5 tumors. Our results suggest that
      strategies enhancing the expression of MHC class I and tumor-associated antigens
      need to be considered in attempts at making vaccination more effective.

PMID- 9139834
TI  - TNF-alpha has no direct in vivo metabolic effect on human muscle.
AB  - Tumor necrosis factor alpha (TNF-alpha) is thought to have a key role in
      metabolic changes of muscle tissue during inflammatory diseases. It is unknown
      whether TNF-alpha affects muscle metabolism directly or whether these changes are
      mediated by secondary mediators. We studied 6 patients undergoing isolated limb
      perfusion with TNF-alpha for irresectable soft-tissue sarcoma or in-transit
      melanomas. Glucose, lactate, ammonia and amino-acid consumption or production
      were measured in the perfusate during 3 perfusion periods: before, after TNF
      alpha and after the combined administration of TNF alpha and melphalan. Arterial
      glucose, lactate, ammonia and amino-acid concentrations were monitored to detect
      metabolic effects of TNF-alpha after it entered the systemic circulation. Glucose
      uptake and lactate release by the limb remained unchanged after the injection of
      TNF-alpha alone, as well as after the combination of TNF-alpha and melphalan.
      Furthermore, glutamine, alanine, phenylalanine, tyrosine and total amino-acid
      release into the perfusate did not increase during TNF-alpha and melphalan
      treatment, indicating that muscle metabolism was not changed. After the isolated
      limb perfusion, TNF-alpha entered the systemic circulation and induced metabolic
      changes resulting in a doubling of arterial lactate concentrations, decreased
      arterial glucose concentrations and decreased arterial amino-acid concentrations.
      Our study shows that regional administration of TNF-alpha alone or in combination
      with melphalan does not directly affect muscle glucose and protein metabolism.
      The data suggest that systemic metabolic changes induced by TNF-alpha are
      mediated through secondary, centrally produced, factors.

PMID- 9139835
TI  - Epstein-Barr virus in gastric carcinoma in Suzhou, China and Osaka, Japan:
      association with clinico-pathologic factors and HLA-subtype.
AB  - Information on geographic differences of Epstein-Barr virus (EBV) positivity and
      association with HLA in gastric carcinoma are limited. Therefore, the association
      of gastric carcinoma with EBV was examined in 118 patients from Suzhou, China,
      where the incidence of nasopharyngeal carcinoma (NPC) is high, and in 216
      patients from Osaka, Japan, where the incidence of NPC is low, NPC being one of
      the EBV-associated carcinomas. Expression of HLA-A2 was also examined in some of
      these cases. The EBV genome was evidenced by PCR and in the tumor cells by in
      situ hybridization in 7/90 and 9/151 of cases from Suzhou and Osaka,
      respectively. Immunohistochemistry revealed that cancer cells in all cases with
      EBV did not express latent membrane protein-I. Type A was found in all cases
      positive for EBV. Among several histologic and clinical factors, only age of
      patients showed a correlation with EBV positivity: patients over 60 showed a
      higher frequency than patients below 60 years of age (p < 0.05). Typing of the
      HLA-A locus was possible in 16 cases positive for the EBV genome: 3 of 4 cases
      from Suzhou and 4 of 7 from Osaka were positive for HLA-A2 products. Severe
      lymphoid cell infiltration was found in 2 of 7 cases and 1 of 4 cases with and
      without the HLA-A2 type, respectively. The reported frequency of EBV positivity
      in Chinese living in Taiwan and in Japanese living in Hawaii is higher than in
      Suzhou, China, and Osaka, Japan, respectively. Our findings suggest that EBV
      association with gastric carcinoma is influenced by environmental and cultural
      factors.

PMID- 9139836
TI  - International incidence rates of invasive cervical cancer before cytological
      screening.
AB  - Huge differences in incidence rates of invasive cervical cancer occur among
      populations. These differences reflect the influences of both etiological
      environmental factors and removal of precursor lesions detected upon screening.
      The purposes of this article are (i) to describe similarities and differences in
      the shapes and magnitudes of age-specific incidence rates of invasive cervical
      cancer before screening had an effect, (ii) to provide baseline data for further
      global study of screening effects, and (iii) to provide baseline incidence data
      for the design of optimal screening programs. To eliminate the impact of
      screening effects, we have selected age-specific incidence rates from times when
      and from populations in which screening was insignificant. The selected rates
      were suitably scaled and compared regarding age at onset of increase in
      incidence, age at peak incidence, and rate of subsequent decline. Despite a 16
      fold difference in incidence rates, all curves had the same basic structure, with
      an increase to a peak followed by a decline or a plateau. Although all
      populations but one had an onset around age 25, 7 European countries showed an
      earlier peak age (mean = 46 vs. 59) and a more rapid decline after the peak than
      most other populations. The common basic shape of the age-specific incidence
      curve, overall, suggests a relatively similar development of invasive cervical
      cancer in different populations. These results illustrate the underlying
      similarities in the markedly different age-specific incidence rates of invasive
      cervical cancer. They also provide a basis for studying screening effects and for
      optimizing screening programs in specific geographic areas.

PMID- 9139837
TI  - The association between lactation and breast cancer in an international case
      control study: a re-analysis by menopausal status.
AB  - In the large, hospital-based, international case-control study of breast cancer
      conducted by MacMahon and colleagues in the 1960s, no protective effect of
      lactation was observed. However, more recent reports have suggested that such an
      association may be limited to pre-menopausal women. Therefore, a re-analysis of
      the data from that original study was performed by menopausal status and with
      control for additional breast-cancer risk factors since identified. Overall, data
      from 4,671 parous pre-menopausal and 7,200 parous post-menopausal women were
      analyzed, from 7 different sites representing areas of high risk (Glamorgan,
      Wales; Boston, USA), moderate risk (Athens, Greece; Slovenia, ex-Yugoslavia; Sao
      Paolo, Brazil), and low risk (Tokyo, Japan; Taipei, Taiwan) of breast cancer. No
      significant effect of lactation was found for pre-menopausal or post-menopausal
      women from the high-, moderate-, or low-risk areas; the center-adjusted, combined
      odds ratio (OR) for having breast-fed was 1.05 (95% confidence interval, 0.86
      1.29) among pre-menopausal and 1.04 (0.88-1.24) among post-menopausal women.
      Moreover, examination of cumulative duration of lactation did not support an
      inverse association between breast cancer and increased length of total breast
      feeding. In conclusion, re-analysis of these data, by menopausal status and
      adjusting for age at first parity, age at menarche, age at menopause, body-mass
      index and years of schooling, did not reveal a protective effect of lactation or
      duration of lactation against breast-cancer occurrence among the pre-menopausal,
      parous women.

PMID- 9139838
TI  - Combined therapy of multidrug-resistant human lung cancer with anti-P
      glycoprotein antibody and monocyte chemoattractant protein-1 gene transduction:
      the possibility of immunological overcoming of multidrug resistance.
AB  - We determined whether transduction of the monocyte chemoattractant protein-1 (MCP
      1) gene into MDR human lung cancer cells affected their tumorigenicity and
      sensitivity to antibody-dependent cellular cytotoxicity (ADCC) reaction mediated
      by the anti-P-glycoprotein (P-gp) monoclonal antibody MRK16. The human MCP-1 gene
      inserted into an expression vector (BCMGSNeo) was transfected into MDR human
      small-cell lung cancer (H69/VP) cells. Monocyte chemotactic activity was found in
      culture supernatants collected from MCP-1-transfected H69/VP cells, but not in
      supernatants of parent and mock-transfected cells. In an in vitro experiment,
      recombinant MCP-1 did not affect monocyte-mediated ADCC against H69/VP cells when
      added to the monocyte culture in either the activation or the effector phase at
      sufficient concentrations to attract and activate monocytes. Tumorigenicity and
      growth rates of MCP-1-producing H69/VP cells in nude mice were similar to those
      of parental cells and mock-transfected cells. However, systemic treatment with
      MRK16 was more effective in inhibiting the formation of tumors by MCP-1-gene
      transfected cells than by mock-transfected cells. Systemic treatment with MRK16
      also inhibited the growth of a mixture (1:1) of MCP-1-producing cells and mock
      transfected cells. These results suggest that combination therapy with MRK16 and
      MCP-1 gene transduction may be a useful immunological strategy to inhibit the
      growth of human MDR cancer cells expressing P-gp.

PMID- 9139839
TI  - Identification of an enriched CD4+ CD8alpha++ CD8beta+ T-cell subset among tumor
      infiltrating lymphocytes in human renal cell carcinoma.
AB  - Three-color immunofluorescence flow-cytometric analysis of freshly isolated tumor
      infiltrating lymphocytes (TIL) from patients with primary renal cell carcinoma
      (RCC) revealed a unique, not previously described TIL subset with a CD3+ CD4+
      CD8alpha++ CD8beta+ phenotype. This subset represented at least 5% of CD3+ TIL in
      15 of 21 patients with clear cell RCC, whereas it was not or only marginally
      represented in patients with papillary RCC or sarcomatoid RCC. In one-third of
      the patients with clear cell RCC, more than 20% of CD3+ TIL and in one patient
      more than half of the CD3+ TIL displayed this phenotype. The occurrence of this
      subset was not associated with pathological stage, tumor diameter, nuclear grade,
      cytogenetic abnormalities or vascular invasion in this patient cohort. When
      present, the CD3+ CD4+ CD8alpha++ CD8beta+ subset was detected in similar
      proportions in tumor tissue and tumor capsula, and it was also detected in
      adjacent non-tumoral renal tissue, albeit in much lower proportions. Despite
      strong cell surface expression of various activation markers (CD69, CD54 and HLA
      DR), CD3+ CD4+ CD8alpha++ CD8beta+ cells displayed no ex vivo cytolytic activity
      in an anti-CD3-redirected cytotoxicity assay. In contrast with CD3+ CD4+ CD8-
      cells from the same tumor sample, they were markedly deficient in IL-2R alpha up
      regulation following anti-CD3 triggering. The possibility that these cells
      represent either anergic cells or a highly specialized effector population with a
      discrete, as yet undescribed function is discussed.

PMID- 9139840
TI  - MLN64 exhibits homology with the steroidogenic acute regulatory protein (STAR)
      and is over-expressed in human breast carcinomas.
AB  - The MLN64 gene, which is localized in q12-q21 of the human chromosome 17, encodes
      a novel protein containing 2 distinct domains. At the N-terminal, MLN64 exhibits
      a potential trans-membrane region, while at the C-terminal, it shares homology
      with the F26F4.4 protein of Coenorhabditis elegans and the steroidogenic acute
      regulatory (StAR) protein, a mitochondrial protein which is involved in steroid
      hormone synthesis. By comparing the C-terminal part of these proteins, we defined
      a novel protein domain, which we termed SHD for "StAR Homology Domain". Of the 93
      primary invasive breast carcinomas that were examined, 14 were found to over
      express MLN64. These 14 tumors also expressed high c-erbB-2 transcript levels,
      which were not detected in the MLN64-negative tumors. MLN64 mRNA and protein were
      specifically detected in malignant cells of breast carcinomas. MLN64 protein was
      localized within bundle-like structures distributed throughout the cell cytoplasm
      and condensed in a perinuclear patch, suggesting an association with a specific
      cell compartment. When the N-terminal part of MLN64 was deleted, MLN64 was
      uniformly distributed in the cell cytoplasm, indicating that N-terminal part is
      involved in the specific cytoplasmic localization of MLN64. The homology between
      the C-terminal part of MLN64 and the functional StAR domain (SHD) suggests that
      MLN64 and StAR, although distributed in different cellular compartments, may both
      play a role in steroidogenesis. In this case, the high levels of MLN64 observed
      in some breast carcinomas could contribute to the progression of these tumors
      through increased intratumoral steroidogenesis.

PMID- 9139841
TI  - CYP1A1, CYP2E1 and GSTM1 polymorphisms are not associated with susceptibility to
      squamous-cell carcinoma of the esophagus.
AB  - We investigated the genetic polymorphisms of CYP1A1, CYP2E1 and GSTM1 in Japanese
      esophageal cancer patients (n = 53) with a histological diagnosis of squamous
      cell carcinoma, to determine whether susceptibility to esophageal cancer is
      associated with these polymorphisms. There were no significant differences in the
      frequency distribution of any one of the 3 polymorphisms between esophageal
      cancer patients and 132 healthy Japanese controls. The genotype distributions in
      tobacco smokers or alcohol drinkers were also quite similar for male patients and
      male controls. The age at onset of esophageal cancer was also similar for
      patients with any genotype of the 3 polymorphisms. We conclude that the 3
      polymorphisms are unlikely to be associated with esophageal cancer
      susceptibility.

PMID- 9139843
TI  - Association of adult glioma with medical conditions, family and reproductive
      history.
AB  - A population-based case-control study of 416 histologically diagnosed, incident
      gliomas in adults was carried out in Melbourne, Australia, to determine whether
      past medical, family or reproductive histories are risk factors for developing
      glioma. A total of 422 controls were selected from the Australian electoral roll
      and matched to cases for age, sex and post code of residence. An increased risk
      of developing glioma was observed among first-born individuals OR (95% CI) 2.0
      (1.4-2.9). It is possible that this effect is due to residual confounding by
      socio-economic status or that it is a chance finding. Alternatively, it may be
      that this is due to some other effect linked to the first pregnancy, such as
      maternal age, birth weight or circumstances of delivery. There was no apparent
      association between the development of glioma and other neuropsychiatric or
      general medical conditions or with family history or reproductive history.
      Allergies (asthma and eczema) were not associated with a decreased risk of
      glioma, as has previously been suggested.

PMID- 9139842
TI  - Antibody reactivities to tumor-suppressor protein p53 and HTLV-I Tof, Rex and Tax
      in HTLV-I-infected people with differing clinical status.
AB  - Since the presence of anti-p53 antibody has been correlated with the mutation and
      accumulation of p53, the aim of this study was to detect anti-p53 antibody and
      understand its correlations with anti-Tof, -Rex, or -Tax antibody reactivity in
      HTLV-I infected people differing in their clinical status. A plasmid (pGEX-Tof)
      was constructed to express Tof recombinant protein (RP) in Escherichia coli.
      Serum samples from 50 asymptomatic carriers (ACs), 50 adult T-cell leukemia (ATL)
      and 50 HTLV-I-associated myelopathyltropical spastic paraparesis (HAM/TSP)
      patients were assayed for reactivity with different RPs by Western
      immunoblotting. The results showed that 2% of ACs, 4% of ATL patients and 6% of
      HAM/TSP patients had anti-p53 antibody. Therefore, anti-p53 antibody is not a
      useful serological marker for clinical management of HTLV-I infected people. Only
      1 HAM/TSP patient had anti-Tof antibody whose specificity was further confirmed
      by antibody competition enzyme immunoassay. This study demonstrates that Tof
      protein is immunogenic in vivo, suggesting that it plays a role in the life cycle
      and pathogenesis of HTLV-I. The rate of anti-Rex antibody among HAM/TSP patients
      was significantly higher than that of ACs or ATL patients. In addition, 50% of
      ACs, 42% of ATL and 98% of HAM/TSP patients had anti-Tax antibody. McNemar's test
      showed that the presence of anti-p53 antibody did not have any correlation with
      the anti-Tax antibody in HTLV-I-infected people, while the correlation between
      anti-p53 and anti-Rex antibodies or anti-p53 and anti-Tof antibodies cannot be
      ruled out in this study.

PMID- 9139844
TI  - High prevalence of human papillomavirus types 16 and 18 in middle-ear carcinomas.
AB  - Chronic suppurative otitis media, averaging 20 or more years of duration, has
      been associated with cancer in this region in 40%-80% of cases. Although human
      papillomaviruses (HPV) have been implicated in many human squamous-cell
      neoplasms, their role in the pathogenesis of middle-ear malignancies remains
      unexplored. In this study, we investigated the presence and subtypes of HPV in
      middle-ear carcinomas. Formalin-fixed and paraffin-embedded tumor tissues were
      sampled for DNA extraction. PCR was done with consensus primers, capable of
      detecting HPV 16, 18, 31, 33, 52b and 58. Typing of the products generated by
      consensus primers was performed with restriction enzyme digestion. It was found
      that a resulting 89% (8/9) of the middle-ear carcinomas contained HPV DNA.
      Coexistence of HPV 16 and 18 was detected in 3 squamous-cell carcinomas. HPV 16
      was detected in 4 squamous-cell carcinomas and 1 adenocarcinoma. The high
      prevalence of high-risk-type HPV in carcinomas of the middle ear suggests that
      viral infection may be an important etiologic component in the carcinogenic
      process.

PMID- 9139845
TI  - Frequent loss of heterozygosity in early non-small cell lung cancers at
      chromosome 9p21 proximal to the CDKN2a gene.
AB  - Deletions involving the chromosome 9p21 region have been reported as frequent
      events in non-small cell lung cancer (NSCLC). To investigate potential tumor
      suppressor gene (TSG) loci within the 9p21 region, which also harbors the
      candidate TSG locus CDKN2a, we studied 32 cases of primary NSCLC for loss of
      heterozygosity (LOH). Tumor and paired normal lung cells were microdissected from
      lung tissue imprints and all samples screened using PCR-LOH analysis with 15 9p
      markers. In addition, 3 NSCLC cell lines and their matched normal lung and tumor
      DNA were similarly analyzed. LOH at the marker D9S259, which is proximal to the
      CDKN2a locus, was found most frequently (52%), while LOH at D9S942, the marker
      closest (5 kb) to the CDKN2a gene, was seen in only 17%. Homozygous loss of
      markers close to CDKN2a was, however, detected in 2 of the 3 cell lines and one
      accompanying tumor sample. We propose that a TSG in the region of deletion
      proximal to the CDKN2a gene within 9p21 may play a significant role in the
      pathogenesis and progression of NSCLC.

PMID- 9139846
TI  - Human papillomavirus type 16 DNA in esophageal carcinomas from Alaska Natives.
AB  - The possible etiological role of human papillomavirus (HPV) in esophageal
      carcinogenesis was evaluated in Alaska Natives in whom the incidence of
      esophageal cancer is 1.3 and 3.8 times higher than in US Caucasian men and women,
      respectively. Fixed paraffin-embedded esophageal tissues from 32 cases of
      squamous-cell carcinoma (SCC) and 3 cases of adenocarcinoma (AC) diagnosed
      between 1957 and 1988 were analyzed by polymerase chain reaction (PCR) and in
      situ hybridization for HPV DNA sequences. Detection of the human beta-globin gene
      by PCR was used as a control for sufficiency of DNA and its potential for
      amplification in the tissue samples. Twenty-five of the tumor tissues were
      considered adequate for PCR analyses; HPV DNA was detected in 10 of 22 SCCs and
      was not found in 3 ACs. Seven of the 10 HPV-positive tissues contained sequences
      from the E6 gene of HPV type 16. Koilocytosis, an epithelial change consistent
      with HPV infection, was found in 80% of the esophageal squamous-cell tumors with
      HPV DNA and in 75% of those without HPV DNA. The detection of amplifiable
      cellular DNA was related to recentness of diagnosis; however, the detection of
      HPV DNA within amplifiable specimens was not related to recentness of diagnosis.
      A 413-bp sequence from the L1 open reading frame of HPV 16 from esophageal tissue
      of 2 patients was identical to sequences previously identified in cervical cells
      from other Alaska Natives. Our results provide molecular evidence of HPV
      infection, especially type 16, in archival esophageal cancer tissues from 45% of
      those patients whose specimens contain adequate DNA for PCR analysis.

PMID- 9139847
TI  - Nitric oxide is an effector molecule in inhibition of tumor cell growth by rIFN
      gamma-activated rat neutrophils.
AB  - This study was designed to determine the effector molecule responsible for the
      tumor-inhibitory activity of rat neutrophils treated with rat recombinant
      interferon gamma (rIFN-gamma) in vitro. The results show that nitric oxide (NO)
      production by neutrophils is dependent on rIFN-gamma concentration, and that
      neutrophil-mediated tumor cytostasis is in turn dependent on the amount of NO. NO
      production and tumor cytostasis by rIFN-gamma-activated neutrophils were
      inhibited completely by N(G) monomethyl-L-arginine (NGMMA), a specific
      competitive NO production inhibitor. Tumor cytostasis was also inhibited by
      oxyhemoglobin (HbO(2)), an NO scavenger. An extracellular oxygen radical
      scavenger, superoxide dismutase (SOD), was found to increase tumor cell
      inhibition by rIFN-gamma-activated neutrophils by a factor of 4. This SOD
      enhanced cytostasis was not even inhibited by catalase. Tumor cytostasis was
      slightly increased by a hydroxyl radical-(.OH) scavenger, dimethylthiourea
      (DMTU), which did not affect NO production by rIFN-gamma-activated neutrophils.
      Our findings suggest that tumor cytostasis of neutrophils activated by rIFN-gamma
      is mediated by L-arginine-derived nitrogen oxidation products, and that O(2)-
      produced by these neutrophils reduces NO-mediated tumor cytostasis at low NO
      concentrations.

PMID- 9139848
TI  - rIFN-gamma-activated rat neutrophils induce tumor cell apoptosis by nitric oxide.
AB  - We have previously shown that 1) neutrophils activated with various cytokines,
      including rat recombinant interferon gamma (rIFN-gamma), inhibit tumor cell
      growth and that 2) nitric oxide (NO) is the effector molecule in tumor inhibition
      by rIFN-gamma-stimulated rat peritoneal exudate neutrophils. In this study, we
      examined the nature of tumor cell death induced by rat peritoneal neutrophils
      activated by rIFN-gamma in order to clarify the mechanism of apoptosis in
      neoplastic tumor cell death. DNA of 3 syngeneic rat tumor cell lines was
      significantly fragmented within 3 hr of incubation in the presence of rIFN-gamma
      activated neutrophils, and this effect was dependent on both the concentration of
      rIFN-gamma and the number of neutrophils. This DNA fragmentation was inhibited by
      L-N-(I-iminoethyl)-ornithine (L-NIO), a NO synthase inhibitor, but not by
      superoxide dismutase (SOD). Tumor cells treated with the activated neutrophils
      were shown by electron microscopy to be apoptotic, exhibiting necrotic features
      with a longer incubation. On the other hand, cytolysis of tumor cells, as
      determined by a [3H]-uridine release assay, was first observed only at 24 hr of
      incubation with the rIFN- gamma-activated neutrophils. Taken together, our
      results suggest that tumor cell apoptosis by activated neutrophils is NO
      dependent and that apoptotic tumor cells undergo necrosis as a secondary process.
      We suggest that tumor cell apoptosis induced by activated neutrophils plays an
      important role in regulation of neoplastic tumor cell growth and death in vivo.

PMID- 9139849
TI  - Determination of tumor-related factors of influence on the uptake of the
      monoclonal antibody 323/A3 in experimental human ovarian cancer.
AB  - The epithelial glycoprotein 40 (EGP40) is an important target in the clinic for
      radioimmunolocalization and monoclonal antibody (MAb)-mediated therapy of cancer.
      We determined which tumor-related factors (including antigen distribution and
      density, vascularization and perfusion) were involved in the uptake of the anti
      EGP40 MAb 323/A3 in 4 different human ovarian cancer xenografts grown s.c. in
      nude mice. The reactivity pattern of 323/A3 in all xenografts in vitro was
      similar and showed a strong and homogeneous distribution of the EGP40 antigen.
      FMa xenografts, however, showed the highest uptake of 323/A3 in vivo, which was
      5.5-, 6.2- and 10.0-fold higher than that in OVCAR-3, Ov.Pe and Ov.Sh xenografts,
      respectively. FMa xenografts contained 2.1- to 3.5-fold more antigen per gram
      protein when compared with the antigen content of the other xenografts. FMa and
      Ov.Sh xenografts demonstrated a better vascularization pattern, whereas Ov.Pe and
      OVCAR-3 xenografts were moderately to poorly vascularized. FMa xenografts were
      also better perfused, as was shown by a 1.6- to 1.8-fold higher uptake of the
      (99m)Tc-labeled blood flow marker hexamethylpropyleneamine oxime (HMPAO). The
      tumor uptake of the non-specific MAb E48 was 2.2- to 11.2-fold lower when
      compared with that of 323/A3, but the sequence of uptake was similar (FMa > OVCAR
      3 = Ov.Pe > Ov.Sh), indicating the lowest extravasation of MAbs in Ov.Sh
      xenograft tissue. Since both the antigen content and the perfusion appeared to be
      important factors of influence on the tumor uptake of 323/A3, attempts were made
      to manipulate these determinants to improve the tumor uptake. Neither gamma
      interferon nor 5-fluorouracil were able to increase EGP40 expression in human
      ovarian cancer cells in vitro. Treatment of tumor-bearing mice with the calcium
      antagonist flunarizine did not result in an improved perfusion, although a slight
      increase in the initial tumor uptake of 323/A3 was observed in Ov.Sh-bearing
      mice. Our results illustrate the relative contribution of various tumor-related
      factors that determine the usefulness of a MAb for imaging and therapy of cancer.

PMID- 9139850
TI  - The cell-specific anti-proliferative effect of reduced glutathione is mediated by
      gamma-glutamyl transpeptidase-dependent extracellular pro-oxidant reactions.
AB  - We have shown earlier that extracellular GSH can exert a cell-specific growth
      inhibitory effect on human tumor cells. In the present study, 2 human ovarian
      carcinoma cell lines (A2780 and IGROV-1) were used to investigate the biochemical
      basis of the GSH growth-inhibitory effect. Whereas cells were resistant, A2780
      cells were sensitive to a 1 hr exposure to GSH, as assessed by the growth
      inhibition assay. Analysis of relevant GSH-dependent enzymes indicated that A2780
      cells had low level of GSH S-transferase, glutathione reductase and gamma
      glutamyl transpeptidase (gamma-GT) activities in comparison with those of IGROV-1
      cells, and GSH peroxidase activity was undetectable in A2780 cells. The GSH
      effect was reversed by catalase and by dithiothreitol, indicating the occurrence
      of oxidative phenomena resulting in the impairment of critical cellular thiols.
      Indeed treatment of cells with H(2)O(2) also resulted in growth inhibition, which
      was more marked in A2780 cells. The gamma-glutamyl acceptor glycylglycine, a co
      substrate for gamma-GT, potentiated the growth-inhibitory effect of GSH, which in
      contrast was decreased by the gamma-GT inhibitors, serine-borate complex and
      acivicin, suggesting that the production of reactive forms of oxygen (probably
      H(2)O(2)) was mediated by cysteinyl-glycine after GSH hydrolysis. The results
      support that the growth-inhibitory effect of low GSH concentration is the result
      of oxidative damage related to extracellular GSH metabolism.

PMID- 9139851
TI  - Early-response gene signalling is induced by angiogenic oligosaccharides of
      hyaluronan in endothelial cells. Inhibition by non-angiogenic, high-molecular
      weight hyaluronan.
AB  - The degradation products of hyaluronan are known to stimulate endothelial-cell
      proliferation and to promote neovascularization associated with angiogenesis,
      whilst native high-molecular-weight hyaluronan is inhibitory to these processes.
      To investigate the cellular signalling pathways coupled to hyaluronan-induced
      responses in angiogenesis, we have analyzed early-response gene expression in
      vitro, in cultured bovine aortic endothelial cells. Angiogenic oligosaccharides
      of hyaluronan induced rapid transient up-regulation of the immediate early genes
      c-fos, c-jun, jun-B, Krox-20 and Krox-24. In contrast, native hyaluronan when
      used alone failed to elicit a significant change in expression of any of the
      genes tested, and when used in combination with angiogenic oligosaccharides of
      hyaluronan, gave a dose-dependent inhibition of induced gene expression. However,
      prior addition of angiogenic hyaluronan, as little as one minute before addition
      of high-molecular-weight hyaluronan, abrogated this inhibition, suggesting that
      positive or negative responses associated with hyaluronan signalling are
      integrated at a very early stage following receptor binding. Conversely, prior
      addition of high-molecular-weight hyaluronan led to an irreversible block in gene
      expression and proliferative response. These data are consistent with native
      hyaluronan antagonizing the angiogenic response in part by blocking a signalling
      cascade at or immediately following ligand-receptor interaction. Finally, we
      demonstrated that chronic exposure to oligosaccharides of hyaluronan is essential
      for cell proliferation, indicating that short-term immediate early-gene
      signalling is insufficient to elicit the proliferation of endothelial cells.

PMID- 9139852
TI  - Chemokines induce migrational responses in human breast carcinoma cell lines.
AB  - Chemokines have been shown to chemoattract and activate different leukocyte
      populations. Here we report the in vitro effect of macrophage inflammatory
      protein (MIP)-1alpha, MIP-1beta, regulated on activation, normal T-cells,
      expressed and secreted (RANTES), monocyte chemotactic protein-1 (MCP-1),
      interleukin-8 (IL-8), interferon inducible protein-10 (IP-10), neutrophil
      activating peptide-2 (NAP-2), growth-related protein (GRO)-alpha and GRO-gamma,
      on the migration of 3 human breast carcinoma cell lines, MCF-7, T47D and ZR-75-1,
      using a microchemotaxis chamber to assess migration across fibronectin-coated
      polycarbonate membranes. MCF-7 cells responded chemotactically to all chemokines
      tested in a pattern which was dose and time dependent, although responses to the
      different chemokines were variable. ZR-75-1 responded to MIP-1beta and GRO-alpha,
      giving maximum migration indices of 3.7 and 5.3, respectively, and exhibited a
      migratory response to MIP-1alpha, IL-8 and MCP-1 although to a lower degree. T47D
      was unresponsive to the chemokines tested, but both MCF-7 and T47D cells bound
      radiolabelled ligands with binding constants (Kd) ranging from 0.6 to 2.2 nM and
      0.6 to 2.1 nM, respectively. The specificity of the chemotactic response of MCF-7
      to MIP-1alpha and MIP-1beta was confirmed using chemokine-specific neutralising
      antibodies and heat denaturation, and was demonstrated to involve G protein and
      cyclic AMP signalling pathways. MIP-1beta and MIP-1alpha were shown to induce
      changes in the organisation of the actin cytoskeleton and the level of F-actin in
      MCF-7 cells, as determined using flow cytometric analysis and confocal
      microscopy. Our results show that breast carcinoma cells can respond to
      chemokines, and suggests a potential role for these molecules in the process of
      tumour cell migration, invasion and metastasis.

PMID- 9139853
TI  - Generation of an anti-tumour immune response in a non-immunogenic tumour: HSVtk
      killing in vivo stimulates a mononuclear cell infiltrate and a Th1-like profile
      of intratumoural cytokine expression.
AB  - Direct delivery of the herpes simplex virus thymidine kinase (HSVtk) gene, in
      combination with the prodrug ganciclovir (GC), has been used for the treatment of
      localised, inoperable tumours. Several groups have shown that when rodent tumours
      are ablated in vivo with suicide genes, anti-tumour immunity can also be
      generated. Hence, this approach may also be useful in treating disseminated
      disease. Here we have studied the mechanisms associated with this anti-tumour
      immunity. In B16 HSVtk+ tumours being killed in vivo with GC treatment, we
      observed the induction of a pronounced intratumoural infiltrate of macrophages,
      CD4+ and CD8+ T cells. In addition, using reverse transcriptase polymerase chain
      reaction, expression of interleukin (IL)-2, IL-12, interferon-gamma (IFN-gamma),
      tumor necrosis factor-alpha (TNF-alpha) and granulocyte/macrophage colony
      stimulating factor (GM-CSF) but not IL-4, IL-6 or IL-10, was observed, a profile
      of cytokine expression which resembles that of a Th1 immune response. To
      complement these findings, we also investigated the mechanisms by which
      expression of HSVtk leads to cell death. Our data show that B16/HSVtk+ cells die
      predominantly by necrosis, rather than apoptosis, on exposure to GC, a process
      which may be associated with the generation of anti-tumour inflammatory
      responses. From these data we propose a model for the induction of anti-tumour
      immunity using suicide genes and discuss the development of improved vectors for
      gene therapy to augment these effects in vivo.

PMID- 9139854
TI  - Control of proteinase expression by phorbol-ester- and Fos-dependent pathways in
      human non-small-cell lung-cancer cells.
AB  - Activation of protein kinase C- (PKC) and Fos/Jun-dependent signal transduction
      pathways are thought to be major effects of oncogene action in different tumor
      systems including human non-small-cell lung carcinoma (NSCLC). We have previously
      shown that the phorbol ester analogue phorbol-myristate-acetate (PMA), which is a
      potent activator of PKC, can induce squamous-type cellular differentiation and
      the expression of proteinases, such as plasminogen activators and pro-cathepsin
      L, in several NSCLC cell lines. To investigate the PMA-dependent effect on
      proteinase secretion in more detail, we have now analysed the role of a
      downstream transmitter of PKC activity in this process, namely Fos, which is part
      of the AP-1 transcription factor in the nucleus. We transfected a cell line
      derived from an undifferentiated squamous-cell lung carcinoma with different
      chimeric fos-estrogen receptor constructs (fos-ER) which makes selective
      activation of this transcription factor possible. The resulting clones were
      treated either with PMA as activator of PKC, or with diethylstilbestrol (DES), an
      estrogen analogue binding to and thereby activating preformed Fos-ER molecules.
      We show that cells treated with either substance undergo similar phenotypic
      changes (change from cuboidal to spindle-cell type) and decrease their doubling
      rates and cloning efficiencies. This is paralleled by the induction of several
      proteinase genes such as t-PA, urokinase, and pro-cathepsins B and L. Contrary to
      activated PKC, Fos in this system seems to be unable to initiate terminal
      squamous-cell differentiation, as assessed by the production of cornified
      envelopes. It is, however, efficient in the stimulation of neutral or lysosomal
      proteinase secretion as determined by Western-blot analysis and zymography. This
      Fos-ER expressing system thus seems to be a valuable tool in the molecular
      dissection of pathways that lead to the activation and secretion of proteinases
      in NSCLC cells.

PMID- 9139855
TI  - Expression and functions of EGF, FGF and TGFbeta-growth-factor family members and
      their receptors in invasive human transitional-cell-carcinoma cells.
AB  - Studies on epidermal-growth-factor-like-, fibroblast- and transforming growth
      factors suggested their implication in tumorigenesis involving effects on tumour
      cell proliferation and migration. In human transitional-cell carcinomas (TCC),
      enhanced expression of TGF alpha and EGF receptors correlated with an aggressive
      phenotype. However, little is known about functions of these growth factors in
      invasive TCCs. In this study, we performed protein- and RNA-expression studies on
      a set of growth factors and their receptors on the newly established invasive
      human TCC cell line designated 1207. The data were correlated with functional
      proliferation and migration studies. Similar expression patterns of many cellular
      markers, growth factors and their receptors were noted both in the original TCC
      tissue and in its derivative cell line, indicating the relevance of this cell
      line to the investigation of growth factor functions on TCC cells. The
      proliferation induction by EGF, TGF alpha, amphiregulin, heregulin alpha, FGF-1
      and FGF-7 correlated with the presence of EGF receptors, c-erbB4 and FGFR2
      (IIIb), respectively. Amphiregulin and heregulin alpha induced the most
      proliferation. In conformity with the low expression of TGF beta receptors I and
      II, TGF beta1, barely inhibited proliferation, while TGF alpha induced invasion
      of 1207 cells into Matrigel. These data support the notion that notably EGF-like
      proteins mediate TCC growth and invasion through autocrine pathways which can be
      reinforced by loss of TGF beta1 regulation.

PMID- 9139856
TI  - Altered intracellular distribution of daunorubicin in immature acute myeloid
      leukemia cells.
AB  - We have used laser-assisted confocal microscopy to evaluate the intracellular
      distribution of daunorubicin (DNR) in acute myeloid leukemia (AML) cell lines and
      fresh AML cells according to their differentiation phenotype. In KG1a, KG1, TF-1
      and HEL cells, which express the early differentiation marker CD34, DNR was
      distributed in perinuclear vesicles which could be associated with the Golgi
      apparatus, as suggested by the distribution of fluorescent probes specific for
      intracellular organelles. In contrast, U937 and HL-60 cells, which display a more
      mature phenotype, exhibited nuclear and diffuse cytoplasmic DNR fluorescence. DNR
      sequestration was not correlated with P-glycoprotein (P-gp) or multidrug
      resistance protein expression. Furthermore, PSC833, a potent P-gp blocker, had
      little effect on drug sequestration in CD34+ AML cells. We also tested the effect
      of metabolic inhibitors, cytoskeleton inhibitors and carboxy-ionophores on DNR
      distribution in both CD34- and CD34+ AML cells. However, only non-specific
      metabolic inhibitors restored nucleic/cytoplasmic distribution in CD34+ cells. In
      these cells, the intracellular distribution of doxorubicin and idarubicin was
      very similar to that of DNR, while the distribution of methoxymorpholinyl
      doxorubicin was nuclear and diffusely cytoplasmic. In fresh AML cells, DNR was
      also concentrated in the perinuclear region in CD34+ but not in CD34- cells.
      However, DNR sequestration was not observed in normal CD34+ cells. Finally, our
      results show that DNR is sequestered in organelles in CD34+ AML cells via an
      active mechanism which appears to be different from P-gp-mediated transport.
      Abnormal DNR distribution may account for the natural resistance of immature AML
      cells to anthracyclines.

PMID- 9139857
TI  - Expression and immunogenicity in rats of recombinant adenovirus 5 DNA plasmids
      and vaccinia virus containing the HTLV-I env gene.
AB  - The complete human T-cell leukemia virus type I (HTLV-I) env gene was inserted
      into an expression cassette containing the adenovirus 5 major late promoter (Ad5
      MLP). Recombinant Ad5-HTLV-I-env was obtained by homologous recombination in 293
      cells simultaneously transfected by the expression cassette and the genomic DNA
      of Ad5. In vitro expression of the HTLV-I-env gene in the recombinant vector was
      detected by immunofluorescence and Western blotting. Functional expression of
      HTLV-I-env was confirmed by syncitium formation specifically in HeLa cells
      infected with Ad5-HTLV-I-env. Two immunization regimens against HTLV-I were
      tested in WKY and Fischer F-344 rats. The first involved WKY rats primed with Ad5
      HTLV-I-env or naked DNA plasmids containing the HTLV-I-env gene and boosted with
      Ad5 containing the HTLV-I-env gp46 gene or with baculovirus-derived recombinant
      gp46. No antibody against HTLV-I was detected, while HTLV-I-specific cytotoxic T
      lymphocytes were recovered from all immunized groups but not from controls. The
      second approach involved Fischer F-344 rats primed and boosted with recombinant
      vaccinia virus containing the HTLV-I-env gene. Such rats developed antibodies
      against the HTLV-I env gp21 and gp46 (non-neutralizing). After challenge with
      human HTLV-I-producing cells (MT-2), both immunization regimens were found to
      induce partial protection.

PMID- 9139858
TI  - Processing-independent assay of serum gastrin for diagnosis of liver metastases
      in the Zollinger-Ellison syndrome. GRESZE (Groupe de Recherche et d'Etude du
      syndrome de Zollinger-Ellison)

PMID- 9139859
TI  - Identification of nude mice in tumorigenicity assays.

PMID- 9139860
TI  - Evaluation of synergism by a novel three-dimensional model for the combined
      action of cisplatin and etoposide on the growth of a human small-cell lung-cancer
      cell line, SBC-3.
AB  - Although the combination of cisplatin and etoposide has been used as standard
      therapy for small-cell lung cancer, it is difficult to demonstrate combination
      effects between cisplatin and etoposide in vitro. We therefore adopted a 3
      dimensional (3-D) model to analyze the combination effects of anticancer drugs,
      and compared the results of analysis by the new 3-D model with those obtained
      from traditional 2-D models for the cisplatin-etoposide combination. In this
      study, using a human small-cell lung-cancer cell line (SBC-3), 3-D model analysis
      clearly identified a relationship depending on the concentrations of both drugs,
      and demonstrated that peak synergy occurred at the higher concentrations of
      cisplatin and etoposide. Antagonistic interactions were noted with a nadir at low
      concentrations of etoposide and cisplatin. In contrast, 2-D models such as
      combination index and isobologam analysis fail to characterize the complex
      interactions between cisplatin and etoposide, since their joint effects are
      concentration-dependent. Combination index (CI) plots show that synergy is
      evident only for molar ratios of cisplatin: etoposide of 2:1 to 1:5. On
      isobologram analysis, synergy could be detected when great inhibitory effects on
      cell growth were present (high endpoint), but not with small inhibitory effects
      (lower endpoints). Thus, either synergy or antagonism may occur, but depend on
      the selection of variables, such as the molar ratios or the endpoints chosen for
      the experiments. This could explain the inconsistency in the in vitro combination
      effects reported to date. The 3-D model, which compensates for the above
      deficiencies of 2-D models, can facilitate rigorous analysis of drug interactions
      over the entire clinical dose range, using microcomputers and sophisticated
      graphics programs. This direct and pragmatic method offers investigators a
      practical new tool with which to analyze drug combinations for cancer
      chemotherapy.

PMID- 9139861
TI  - Immunohistochemical analysis of integrin alpha vbeta3 expression on tumor
      associated vessels of human carcinomas.
AB  - Expression of the alpha vbeta3 integrin is upregulated on sprouting endothelia.
      Systemic application of antibody or peptidic inhibitors of alpha vbeta3 function
      disrupts tumor angiogenesis and reduces growth and invasiveness of human tumors
      in animal models. We systematically investigated alpha vbeta3 expression on tumor
      associated vessels of 4 different human epithelial tumors and the corresponding
      normal tissues by means of immunohistochemistry on frozen sections using the
      alpha vbeta3-complex specific monoclonal antibody LM609. Variable levels of LM609
      staining were found in all carcinoma lesions. A considerable number of tumor
      tissues (35/50) expressed alpha vbeta3 on more than 50% of their vessels.
      Inflammatory infiltrates and the possibly hypoxic conditions near necrotic areas
      of tumors were accompanied by an increased alpha vbeta3 expression. Remarkably,
      the vasculature in apparently normal tissue also stained for alpha vbeta3.
      However, the percentages of stained vessels and their staining intensity were
      lower than in neoplastic tissues. Besides the vascular alpha vbeta3 expression,
      several extravascular cell types stained positive, in both normal and tumor
      specimens. Taken together, our findings show a considerable number of colon,
      pancreas, lung and breast carcinoma lesions with many alpha vbeta3-expressing
      vessels that could be targets for anti-alpha vbeta3-therapy.

PMID- 9139862
TI  - Cytotoxic T-cell clone against rectal carcinoma induced by stimulation of a
      patient's peripheral blood mononuclear cells with autologous cultured tumor
      cells.
AB  - In an effort to establish cytolytic T lymphocytes (CTLs) against colorectal
      carcinoma (CRC) by stimulating patients' lymphocytes with autologous tumor cells,
      we used peripheral blood mononuclear cells (PBMC) from a patient with minimal
      residual rectal carcinoma following removal of the primary lesion and involved
      regional lymph nodes as a source to generate CTLs in culture. A CTL line and
      clone were established from the patient's PBMC following stimulation of PBMC with
      autologous, cultured tumor cells and interleukin-2. The CTL line and the clone
      consisted predominantly of CD4+ lymphocytes. The CTL clone expressed two T-cell
      receptor variable alpha chains (V alpha11 and V alpha22) and one beta chain
      (Vbeta14). The cytokine secretion pattern of the CTL line was of the Th1-type.
      Both the CTL line and the clone lysed the autologous rectal carcinoma cells, but
      not the allogeneic, partially human lymphocyte antigen (HLA)-matched or
      nonmatched CRC cells, autologous Epstein-Barr virus-transformed B cells, K562
      (natural killer target) cells or Daudi (lymphokine-activated killer target)
      cells. Lysis of autologous tumor cells most likely was HLA class I-restricted.
      Our unique success in generating CTLs against this tumor type may rest in the
      inclusion of a patient with minimal residual, rather than advanced, disease.

PMID- 9139863
TI  - Extratumoral breast tissue in breast cancer patients: a multinational study of
      variations with age and country of residence in low- and high-risk countries. WHO
      Collaborative Study of Neoplasia and Steroid Contraceptives.
AB  - With the aim of elucidating the relationships between breast cancer, risk factors
      and benign breast changes, extratumoral breast tissue in 1,506 women from the WHO
      Collaborative study of neoplasia and steroid contraceptives was studied
      histologically. Patients came from 3 countries with a high incidence of breast
      cancer (Israel, East Germany and Australia) and 6 low-risk countries (Thailand,
      China, Philippines, Mexico, Chile and Colombia). Ductal atypia, ductal
      hyperplasia, adenosis, lobular atypia, apocrine metaplasia, apocrine hyperplasia,
      apocrine atypia, cysts, duct ectasia, inflammatory reaction, calcification,
      lactational change and epithelial-stromal ratio were classified as
      absent/mild/moderate/marked. Prevalence odds ratios were calculated by logistic
      regression analyses. Increasing frequency with age was found for ductal
      hyperplasia, sclerosing adenosis, apocrine metaplasia and cysts, while adenosis,
      lactational change and the epithelial-stromal ratio decreased with age. No
      significant difference between high- and low-risk countries was found for ductal
      hyperplasia or sclerosing adenosis. Compared with cases from high-risk countries,
      those from low-risk countries had a significantly lower prevalence of apocrine
      metaplasia, apocrine hyperplasia and cysts, and a significantly higher prevalence
      of ductal atypia. When seen in conjunction with other studies, the results
      suggest that ductal hyperplasia and sclerosing adenosis have similar roles in
      cancer development in high- and low-risk countries and that the factors
      responsible for international differences in breast cancer may exert their effect
      by influencing the initial development of these changes. They also suggest a
      delayed progression from noninvasive to invasive carcinoma in low-risk countries.

PMID- 9139864
TI  - Esophageal and gastric carcinoma in Norway 1958-1992: incidence time trend
      variability according to morphological subtypes and organ subsites.
AB  - The occurrence of adenocarcinoma (AC) of the esophagus and gastric cardia has
      shown large increases in many but not all examined populations. This trend is in
      contrast with a decrease in distal gastric AC and a relative stability of
      esophageal squamous cell carcinoma. Our study aimed to describe esophageal and
      gastric carcinoma time trends in the Norwegian population between 1958 and 1992
      based on data from the Cancer Registry of Norway. Estimated esophageal AC rates
      have accelerated over the study period, reaching average annual increases of 17%
      in men and 14% in women between 1983 and 1992. The occurrence of esophageal
      squamous cell carcinoma was relatively stable in both sexes. Proximal gastric
      cancer rates were stable in males and decreased somewhat in females. Distal
      gastric tumors showed decreases in both sexes, but were more pronounced in
      females. The strong increase in esophageal AC incidence parallels similar
      increases in the United States and some other countries. Although the observed
      increase may be explained to some extent by a shift in the classification of
      esophago-cardial adenocarcinomas, the figures are compatible with a real
      increase. AC of the esophagus, the proximal stomach and the distal stomach
      exhibit different epidemiological features, both in terms of sex ratios and time
      trends, suggesting risk factor differences between the subsites.

PMID- 9139865
TI  - Epstein-Barr virus (EBV) gene expression in lymphoid B cells during acute
      infectious mononucleosis (IM) and clonality of the directly growing cell lines.
AB  - We examined the patterns of viral gene expression in acute infectious
      mononucleosis (IM) patients and the clonality of the directly growing EBV
      carrying cell lines. Both low- and high-density EBV-carrying B cells obtained
      from the patients' tonsils expressed EBNA1, EBNA2 and LMP1. Like LCLs and
      immunoblastic B-cell lymphomas, the in vivo EBV-carrying low-density cells used
      only the latency III program for viral gene expression. The in vivo EBV-carrying
      high-density B cells used both the latency I program, as indicated by the QUK-,
      and the latency III program, as indicated by the YUK-EBNA1. This suggests that
      the lymphoid tissues contained not only proliferating immunoblasts but also cells
      programmed for latent viral persistence in vivo. EBV-carrying cells that grew
      directly into permanent cell lines in the presence of virus-neutralizing antibody
      and a late viral inhibitor were polyclonal, as indicated by JH rearrangement. Two
      of the high-density-derived lines had identical JH and TR patterns, indicating a
      common parental origin. Our investigation indicates that EBV-carrying cells
      divide and survive in a fully competent immune system during the outbreak of
      acute IM.

PMID- 9139866
TI  - Frequent detection of aberrant RNA transcripts of the CDKN2 gene in human gastric
      adenocarcinoma.
AB  - The tumor-suppressor gene CDKN2 (p16/INK4A/MTS1) is frequently altered in human
      gastric-cancer cell lines. However, mutation of the CDKN2 gene in primary human
      gastric-carcinoma tissues as seen through genomic DNA analysis has rarely been
      reported. In this study, a method combining reverse transcription and nested
      polymerase chain reaction was developed to detect different RNA transcripts of
      the CDKN2 gene in human gastric cancers. The results showed that, besides the
      wild-type CDKN2 transcript, 5 of 11 (45.5%) diffuse-type and 3 of 10 (30%)
      intestinal-type primary gastric adenocarcinoma had aberrant CDKN2 RNA
      transcripts. Among these 8 tumorous specimens with abnormal CDKN2 RNA
      transcripts, 6 had intragenic deletions of part of both CDKN2 exons 1 and 2,
      including 1 case which had an additional inserted sequence from part of CDKN2
      intron 2. In addition, 1 case had a deletion of part of CDKN2 exon 1 and 1 case
      had its entire exon 2 deleted. In contrast, matched normal gastric mucosal
      tissues from the same patients did not have any aberrant CDKN2 RNA transcript.
      Furthermore, CDKN2 exon 1 or 2 genomic DNA from all the gastric-carcinoma tissues
      were PCR-amplified and sequenced and no genetic alteration was detected.
      Therefore, alteration and heterozygous expression of CDKN2 appears to be involved
      in the pathogenesis of human gastric cancers.

PMID- 9139867
TI  - The E-cadherin gene is silenced by CpG methylation in human hepatocellular
      carcinomas.
AB  - Our study was designed to clarify the significance of silencing the E-cadherin
      gene, which is located on 16q22.1, due to CpG methylation during
      hepatocarcinogenesis. The CpG methylation status of primary hepatocellular
      carcinomas (HCCs) and corresponding liver tissues showing chronic hepatitis or
      cirrhosis, which are widely considered to be precancerous conditions, were
      assessed by digesting DNA with methylation-sensitive and non-sensitive
      restriction enzymes. CpG methylation around the promoter region of the E-cadherin
      gene was detected in 46% of liver tissues showing chronic hepatitis or cirrhosis
      and 67% of HCCs examined. Immunohistochemical examination revealed reduced E
      cadherin expression in 59% of HCCs examined. CpG methylation around the promoter
      region correlated significantly with reduced E-cadherin expression in HCCs (p <
      0.05). CpG methylation around the promoter region, which increases during the
      progression from a precancerous condition to HCC, may participate in
      hepatocarcinogenesis through reduction of E-cadherin expression, resulting in
      loss of intercellular adhesiveness and destruction of tissue morphology.

PMID- 9139868
TI  - Risk of endometrial and breast cancer in patients with diabetes mellitus.
AB  - Diabetes mellitus patients have metabolic and endocrine alterations that could
      contribute to an increased incidence of hormone-related cancers. We assessed the
      incidence of endometrial and breast cancer among 80,005 women and the incidence
      of breast cancer among 73,847 men (total of 153,852 patients) identified in the
      Swedish In-patient Register as having been hospitalized for diabetes mellitus in
      the period 1965-1983. These patients underwent follow-up through 1989 via the
      Swedish Cancer Register and other nation-wide Swedish registers. The outcome
      measures were standardized incidence ratios (SIR) based on age-, sex- and
      calendar period-specific incidence rates from the entire Swedish population. To
      minimise the effect of selection bias, we excluded from the calculation of
      incidence ratios the first year of observation and cases diagnosed incidentally
      at autopsy. Only first cancers were considered for the estimates. A total of 328
      endometrial cancers (SIR = 1.8; 95% confidence interval [CI] = 1.6-2.0), 1,145
      female breast cancers (SIR = 1.3; 95% CI = 1.2-1.4) and 13 male breast cancers
      (SIR = 2.0; 95% CI = 1.0-3.4) were observed. We conclude that compared with the
      general population, patients with diabetes mellitus have an increased incidence
      of endometrial and breast cancers.

PMID- 9139870
TI  - p53 mutation spectrum in Japanese Bowen's disease suggests a role for mutagens
      other than ultraviolet light.
AB  - The Japanese have a much lower incidence of nonmelanoma skin cancers (NMSCs) than
      Caucasians, presumably due in part to their skin type conferring relative
      protection from ultraviolet light radiation (UVR). To examine the contribution of
      environmental or endogenous mutagens other than UVR, which are expected to be
      relatively more important to the overall burden of NMSCs in the Japanese, we
      directly sequenced exons 5-8 of the p53 tumour suppressor gene in 29 Japanese
      patients with Bowen's disease, an in situ squamous-cell carcinoma of the skin. We
      found 9 mutations, including two CC:GG to TT:AA tandem transitions (presumably
      related to UVR), 3 transversions and 4 frameshift mutations. The mutational
      spectrum seen in our study contrasts with that we previously found in Bowen's
      disease from a Caucasian population, in keeping with a different aetiology for
      Bowen's disease in the respective populations. The unexpectedly high prevalence
      of frameshift mutations suggests that environmental mutagens other than UVR that
      preferentially induce deletion or insertion mutations may play an important role
      in the tumorigenesis of Japanese Bowen's disease, and warrants further
      investigation.

PMID- 9139869
TI  - A one-step DGGE scanning method for detection of mutations in the K-, N-, and H
      ras oncogenes: mutations at codons 12, 13 and 61 are rare in B-cell non-Hodgkin's
      lymphoma.
AB  - Mutations in the N-, K-, and H-ras genes are key events in the process of
      carcinogenesis of many human cancers and may serve as important targets for
      therapeutic intervention. We developed a simple diagnostic method that in one
      step and within 5 hr determines the mutational status of any of the 3 ras genes
      in a given tumor sample. The method combines polymerase chain reaction (PCR) with
      denaturing gradient gel electrophoresis (DGGE) and allows simultaneous mutation
      scanning of 6 regions covering "hot-spot" codons 12, 13 and 61 of the 3 ras
      genes. The sensitivity of the assay was demonstrated by the analysis of control
      mutations, either naturally occurring or created by site-directed mutagenesis. We
      further demonstrate that unambiguous identification of ras mutations can be
      achieved by heteroduplex analysis in denaturing gradient gels, circumventing
      sequence analysis. We applied the method to establish the mutational status of
      all 3 ras genes in 123 samples of B-cell non-Hodgkin's lymphoma. Altogether, one
      diffuse large B-cell lymphoma and one B-cell chronic lymphocytic leukemia (B-CLL)
      harbored a mutation (G12S and G12A, respectively) in the K-ras gene, and one B
      CLL harbored a mutation (Q61R) in the N-ras gene. We therefore conclude that ras
      mutations only contribute rarely, if at all, to carcinogenesis in B-cell non
      Hodgkin's lymphoma.

PMID- 9139871
TI  - Survival analysis in families affected by hereditary non-polyposis colorectal
      cancer.
AB  - Previous survival studies suggested a better prognosis of hereditary nonpolyposis
      colorectal cancer (HNPCC) patients compared with the sporadic counterpart. In the
      present study we evaluated the clinical outcome of HNPCC patients with respect to
      that of patients with colorectal cancer recorded in a population-based cancer
      registry. We assessed survival of 85 colorectal cancer patients from 24 unrelated
      families defined as having HNPCC according to the criteria of the International
      Collaborative Group, for whom adequate information on subject- and tumor-related
      parameters and a 5-year follow-up (cancer diagnosis from 1980-1989) were
      available. Three hundred and seventy-seven colorectal cancer patients, registered
      from 1984-1986, with a 5-year follow-up, were used for comparison. Colorectal
      cancer-specific 5-year survival rates were 55.2% and 42.5% for HNPCC and non
      HNPCC, respectively. Using Cox regression analysis, tumor staging and location
      were independently associated with survival, whereas HNPCC diagnosis was not.
      Stage II HNPCC cases exhibited a better prognosis than non-HNPCC patients. By Cox
      regression analysis, none of the variables were significantly related to
      survival. Both overall and stage II HNPCC cases showed a survival advantage in
      comparison with non-HNPCC patients. However, the difference disappeared when
      clinical and pathological variables were controlled for with a Cox regression
      analysis.

PMID- 9139872
TI  - Inhibition of the growth of pre-established subcutaneous tumor nodules of human
      prostate cancer cells by single injection of the recombinant adenovirus p53
      expression vector.
AB  - We have previously described potent growth-inhibitory effect of a recombinant
      adenovirus expressing wild type p53 (AdWTp53) in metastatic prostate cancer cells
      via activation of cellular p53 pathways. We have extended these observations to
      analyze the effects of AdWTp53 on primary cultures of radical prostatectomy
      specimens (RPS) and have also evaluated the gene therapeutic potential of the
      AdWTp53 in a nude mice model. Infection of primary cultures of prostate cancer
      specimens resulted in about 80% cell growth inhibition in comparison with
      cultures treated with control adenovirus dl312. Single injection of AdWTp53 into
      pre-established tumor nodules of DU145 prostate cancer cells suppressed tumor
      growth significantly (p = 0.0407) as determined by comparison of tumor volumes of
      the AdWTp53-treated vs. control vector (dl312) or PBS-treated groups. Moreover,
      there was no significant difference in tumor growth inhibition between single vs.
      multiple injections of AdWTp53. Our observations support the potential of AdWTp53
      for gene therapy of prostate cancer.

PMID- 9139873
TI  - Mouse fibroblast activation protein: molecular cloning, alternative splicing and
      expression in the reactive stroma of epithelial cancers.
AB  - The growth of solid neoplasms requires the recruitment of a supporting stroma. In
      most epithelial cancers, this stromal compartment comprises newly formed blood
      vessels and abundant, reactive stromal fibroblasts. Tumor stromal fibroblasts are
      not transformed but differ from resting fibrocytes in normal adult tissues by an
      altered pattern of gene expression. In human cancers, this includes induction of
      the cell-surface-bound fibroblast-activation protein (FAP), a member of the
      serine protease family encoded by the FAP gene on chromosome 2. In this study, we
      have cloned a complementary DNA for Fap, the murine homologue of FAP. The
      predicted murine FAP protein, mFAP, shares 89% amino-acid-sequence identity with
      human FAP, including a perfectly conserved catalytic triad. Cultured mouse embryo
      fibroblasts and mouse embryonic tissues were found to express Fap transcripts. In
      addition, the host-derived, fibroblast-rich stroma of human epithelial-cancer
      xenografts grown in immunodeficient mice also expresses Fap. Sequencing of
      reverse-transcription-PCR products indicates that 3 distinct Fap splice variants
      can be detected in tissues. Our findings suggest a close similarity in structure
      and tissue expression of FAP in different species. By extending the analysis of
      FAP to the mouse, new in vivo test systems become available for genetic and
      therapeutic manipulations and for the study of FAP regulation and function in
      embryonic development and in epithelial cancers.

PMID- 9139874
TI  - Invasion of human colorectal carcinoma cells is promoted by endogenous basic
      fibroblast growth factor.
AB  - The growth-stimulatory and invasion-promoting effects of basic fibroblast growth
      factor (bFGF) were examined in 2 series of related human colon carcinoma cell
      lines (HCT116A, HCT116B and 20-10-1 as well as and LS180, LS174T and ARK1A) that
      exhibit different invasive potentials. The invasive cell lines 20-10-1 and ARK1A
      grew more rapidly than their non-invasive counterparts; exogenously added bFGF
      stimulated the proliferation of all the cells. When extracts of the cells were
      fractionated on columns of heparin-Sepharose, bFGF-like activity was found in
      extracts from each cell line. The amount of bFGF-like growth-stimulatory activity
      was greater in the more invasive cells: the invasive cells 20-10-1 contained 35
      fold more activity than the non-invasive HCT116A cells, and the ARK1A cells
      contained 15-fold more activity than LS180 cells. Relatively small amounts of
      bFGF-like activity were recovered from medium conditioned by the invasive cells.
      The bFGF-like growth-stimulatory activity from the cell extracts was neutralised
      by an antibody to bFGF, and immunoblotting revealed the presence of an 18 kDa
      immunoreactive polypeptide, consistent with the presence of bFGF in the cell
      extracts. Exogenously added bFGF caused the usually non-invasive HCT116A cells to
      invade collagen gels. The HCT116B and 20-10-1 cells that were naturally invasive
      in a collagen gel assay also showed increased levels of invasiveness in the
      presence of bFGF, but an antibody that neutralised the activity of bFGF reduced
      the constitutive invasiveness of these cells. Our results suggest a causal
      relationship between the endogenous production of bFGF and the invasive potential
      of human colon carcinoma cells.

PMID- 9139875
TI  - Translation initiation factor eIF-4A1 mRNA is consistently overexpressed in human
      melanoma cells in vitro.
AB  - The oncogenic potential of translation initiation factors (eIF-4E and eIF-2alpha)
      has been described in previous studies leading to the definition of translational
      oncogenes. Two previously isolated cDNA clones, expressed differently in human
      melanoma cells and normal human melanocytes, were identified in this study as
      coding for the translation initiation factor eIF-4A1. Northern-blot analysis
      revealed consistent overexpression of eIF-4A1 mRNA in a panel of 14 melanoma cell
      lines (on an average 5.6 times higher than in cultures of normal human
      melanocytes). In contrast, the mRNAs of the other group-4 translation initiation
      factors (eIF-4A2, eIF-4B, eIF-4E and eIF-4gamma) were less and not consistently
      elevated. Cultures of congenital melanocytic nevi exhibited intermediate
      expression of eIF-4A1. Thus, eIF-4A1 overexpression seems to be an important
      feature of melanoma cells and might contribute to their malignant transformation.

PMID- 9139876
TI  - Discrimination of fibroblast subtypes by multivariate analysis of gene
      expression.
AB  - Fibroblasts and myofibroblasts from normal, fibrotic or tumoral breast tissues
      present multiple quantitative differences in gene expression even when grown in
      isolation. We were therefore prompted to investigate whether one could recognize
      various subtypes by their constitutive-gene expression profile. Quantitative
      autoradiographic data for 34 constitutively expressed transcripts were submitted
      to multivariate analysis of variance, followed by discriminant analysis and
      single linkage cluster analysis. Models assuming up to 8 putative fibroblast
      subtypes (among fibroblasts or myofibroblasts from breast skin, normal mammary
      stroma, tumor-adjacent "normal" stroma, post-radiation fibrosis lesions and
      benign or malignant tumors) and an epithelial-cell group used as an internal
      control resulted in 100% correct classification. Myofibroblasts from various
      origins clustered close to, although distinctly apart from, their corresponding
      alpha-smooth-muscle-actin-negative counterparts. Malignant tumor fibroblasts were
      phenotypically more distant from normal cells compared with other pathological
      types. Our results support the hypothesis of co-adaptive transformation of
      stromal and epithelial tissues during breast tumoral development and suggest that
      different types of fibroblasts give rise to different types of myofibroblasts.
      Discriminant analysis of quantitative molecular variation may be considered for
      the development of a powerful artificial-intelligence method for cell typing and
      should be particularly useful when no reliable discrete molecular markers are
      available.

PMID- 9139877
TI  - Relationship between the parameters cellular differentiation, doubling time and
      platinum accumulation and cisplatin sensitivity in a panel of head and neck
      cancer cell lines.
AB  - Patients with head and neck squamous cell carcinoma (HNSCC) treated with
      cisplatin show a large inter-individual variation in tumor response. Little is
      known about factors that contribute to this variation. The aim of our study was
      to correlate the sensitivity to cisplatin with a number of cellular parameters
      using a panel of 10 human HNSCC cell lines. A 7-fold variation in response after
      72 hr of exposure to cisplatin as determined in a colorimetric proliferation
      assay was observed. The IC50 values did not correlate with the DNA index, the
      cellular doubling time or the expression of differentiation markers.
      Intracellular platinum (Pt) concentrations were measured by atomic absorption
      spectroscopy after exposing the cells to 10 microM cisplatin for 1-72 hr. The
      intracellular Pt levels increased up to 24 hr. One cell line, derived from the
      tumor of a patient previously treated with radiotherapy, accumulated much more Pt
      than the other cell lines. For these other cell lines, a significant positive
      correlation was found between Pt accumulation and sensitivity. In conclusion,
      cisplatin-induced growth inhibition in HNSCC in vitro is generally positively
      correlated with cellular Pt levels. However, the fact that occasionally cancer
      cells can survive despite high intracellular Pt levels indicates that additional
      parameters are needed to explain a response unequivocally.

PMID- 9139878
TI  - Resistance to IL-1 anti-proliferative effect, accompanied by characteristics of
      advanced melanoma, permits invasion of human melanoma cells in vitro, but not
      metastasis in the nude mouse.
AB  - We reported earlier that IL-1 inhibits the growth of human melanoma cells (A375
      6), and that these cells become resistant to IL-1 after prolonged periods of
      culture. The resistant cells constitutively produce IL-alpha and IL-6 with IL-6
      production was induced by endogenous IL-1 in an autocrine manner. The cells are
      also resistant to IL-6 anti-proliferative effects. In the present study, we show
      that the resistant clones exhibited up-regulated expression of intercellular
      adhesion molecule 1 (ICAM-1) and vitronectin receptor (integrin alpha(v)beta3)
      when compared with the IL-1-sensitive clone, A375-6. Moreover, these IL-1
      resistant clones exhibited many other metastatic characteristics, such as
      expression of IL-8 mRNA, production of matrix metalloproteinases (MMP-2 and MMP
      9), and augmented invasion activity. However, contrary to our expectations, the
      IL-1-resistant cells did not exhibit experimental metastasis in a nude-mouse
      model, similarly to the IL-1-sensitive parental A375-6 cell line. In contrast,
      the highly metastatic clone A375-SM exhibited alpha(v)beta3 expression at a level
      comparable to that of the IL-1-resistant cells, but expressed low or no ICAM-1,
      metalloproteinase and displayed little in vitro invasion activity. These results
      show that the metastatic characteristics of IL-1-resistant cells are not
      sufficient to produce metastasis in vivo and suggest that these resistant clones
      may provide a good model system for characterizing the molecular mechanisms of
      metastasis.

PMID- 9139879
TI  - Stimulation of interleukin-11 production from osteoblast-like cells by
      transforming growth factor-beta and tumor cell factors.
AB  - Bone is one of the most common sites of metastasis in melanoma and breast cancer
      cells. Human melanoma (A375M) and human breast cancer (MDA-MB-231) cells form
      osteolytic bone metastasis in vivo when these tumor cells are injected into the
      left ventricles of BALB/c nude mice. These tumor cells promote bone resorption in
      the in vitro neonatal murine calvaria organ culture system by indirectly
      stimulating the production of a bone resorption-inducing factor (or factors) from
      human osteoblast-like cells. This secreted factor was identified as interleukin
      11 (IL-11). Although many cytokines and hormones were associated with IL-11
      production from osteoblasts, transforming growth factor-beta (TGF-beta) was found
      to be involved in the promotion of IL-11 production from osteoblasts, because the
      addition of a neutralizing anti-TGF-beta antibody decreased the production of IL
      11. However, these tumor cells did not produce TGF-beta by themselves. We found
      that they enhanced IL-11 production by activating latent TGF-beta produced from
      osteoblast-like cells. Our results indicate that metastatic tumor cells induce
      osteolysis by activating TGF-beta, which leads IL-11 production from osteoblasts
      to promote bone resorption.

PMID- 9139880
TI  - The advantage of residualizing radiolabels for targeting B-cell lymphomas with a
      radiolabeled anti-CD22 monoclonal antibody.
AB  - CD22 antibodies (Abs) bound to B-cell lymphomas are known to be internalized and
      catabolized rapidly. Therefore, it would be expected that use of CD22 as a target
      for radioimmunotherapy should be enhanced by the use of "residualizing"
      radiolabels, which are trapped within the cell after catabolism of the Ab to
      which they had been conjugated. Our study was intended to evaluate this
      hypothesis using Ab LL2. In initial experiments, we found that LL2 binding was
      strongly temperature dependent, with approximately 15-fold greater binding at 37
      degrees C than at 0 degrees C. A series of experiments suggested that this
      difference is due to a conformational change in the antigen at low temperature,
      so that the LL2 epitope is partially blocked. In vitro, residualizing labels
      including 125I-dilactitol tyramine and 111In-DTPA-were retained by cells much
      longer than a conventional iodine label. In vivo, residualizing labels also
      showed a marked advantage in terms of uptake by Ramos B-cell lymphoma xenografts
      in nude mice. However, the absolute Ab uptake by xenografts was quite low, in
      comparison with results obtained with many carcinoma xenografts, which appears to
      be due in part to vascular properties of the B-cell lymphoma xenografts.

PMID- 9139881
TI  - Liver metastasis formation by laminin-1 peptide (LQVQLSIR)-adhesion selected B16
      F10 melanoma cells.
AB  - Laminin-1, a major basement membrane glycoprotein, promotes tumor cell
      malignancy. Incubation of B16-F10 melanoma cells with a peptide containing an
      active sequence in laminin-1, designated AG-73 (leu-glu-val-glu-leu-ser-ile-arg;
      LQVQLSIR), enhances in vitro adhesion, migration, invasion and gelatinase
      production and in vivo lung colonization and metastases to the liver. In the
      current study, we have tried to define the mechanism of enhancement of liver
      metastases induced by AG-73 using B16-F10 murine melanoma cells selected for
      adhesion on AG-73-coated dishes. Cells were sequentially selected for adhesion
      more than 30 times and then characterized. AG-73 selected cells had much longer
      cytoplasmic processes and occasionally formed nodular aggregates. AG-73 selected
      cells attached 1.2- to 1.5-fold better to both AG-73 and laminin-1, were able to
      invade through the Matrigel-coated filter up to 6-fold more, grew s.c. 1.5-2
      times faster, produced twice the number of lung colonies, and showed more liver
      nodules (12 of 28 vs. 1 of 27) than parental cells. Our data demonstrate that the
      enhanced malignant phenotype of B16-F10 cells can be observed in the absence of
      added peptide with the adhesion-selected cells.

PMID- 9139882
TI  - Autocrine transformation by fibroblast growth factor 9 (FGF-9) and its possible
      participation in human oncogenesis.
AB  - Transfection of human fibroblast growth factor 9 (FGF-9) cDNA into mouse BALB/c
      3T3 clone A31 cells led to morphological transformation of the cells and foci
      formation 4 weeks later. Isolated transformants had a higher saturation density
      than parental A31 cells, could grow in soft agar, and secreted FGF-9 into the
      culture supernatant. The introduction of FGF-9 N33 cDNA, which encodes a
      truncated protein that has 33 N-terminal amino acids deleted and has the same
      mitogenic potency as FGF-9, failed to lead to foci formation. Although FGF-9 is a
      secretory protein, it does not have a typical secretory signal sequence, and the
      secreted protein retains the full sequence coded in the cDNA except for the
      initiating methionine. The produced FGF-9 N33 was not secreted and remained
      within the cell. It is possible that FGF-9 has an uncleavable signal sequence
      within the first 33 N-terminal amino acids. All of the phenotypes acquired by
      transformation could be arrested by treatment with a neutralizing anti-human FGF
      9 monoclonal antibody (MAb) 150-59. Additionally, transformants formed tumors in
      nude mice. Injection of MAb 150-59 suppressed tumor formation in nude mice and
      caused existing tumors to regress. Our results suggest that the cellular
      transformation mediated by FG F-9 is produced by autocrine stimulation. We have
      detected FGF-9 production in the human tumor cell lines glioma NMC-G1, from which
      FGF-9 was originally purified, and stomach carcinoma AZ-521. The growth of NMC-G1
      was not affected by MAb 150-59, but that of AZ-521 was arrested by MAb 150-59 in
      the presence of heparin. Moreover, the growth of the AZ-521 cell tumor in nude
      mice could be partially arrested by antibody treatment. The possibility of a
      participation of FGF-9 in the formation of human tumors is suggested.

PMID- 9139883
TI  - Apoptosis in rat prostatic adenocarcinoma is associated with rapid infiltration
      of cytotoxic T-cells and activated macrophages.
AB  - Rats transplanted with the androgen-sensitive, syngeneic Dunning R3327 PAP
      prostatic tumor were castrated and treated with estrogen or vehicle for 4, 12 and
      24 hr and for 6 weeks. Tumor growth was retarded by castration and further
      inhibited by estrogen. Immediately after castration, an increased number of
      activated macrophages and T-cells were found in parallel with increasing
      apoptotic tumor cells. Administration of an immunosuppressive drug, FK 506,
      abolished the growth-inhibitory effects of castration and estrogen. The tumor
      growth rate correlated negatively with the number of R73- and OX8-positive T
      cells and NK cells and with the percentage of ED3-positive macrophages. There was
      a positive correlation between the percentage of TdT-mediated-dUTP nick end
      labeling (TUNEL)-positive apoptotic cells and that of ED3-positive cells. Our
      results suggest that apoptosis of prostatic carcinoma cells induced by endocrine
      treatment in vivo is partly due to a rapid infiltration by immunocompetent cells.

PMID- 9139884
TI  - Effects of tamoxifen and interferon-beta or the combination on tumor-induced
      angiogenesis.
AB  - Inhibition of angiogenesis by anti-tumor agents may play a role in tumor growth
      arrest. Tamoxifen and interferon-alpha/beta (IFN-alpha/beta) exhibit potentiated
      anti-proliferative activity against tumor cells. However, additional host
      mediated effects such as modulation of angiogenesis may also inhibit tumor growth
      in vivo. The effect of tamoxifen and IFN-beta on angiogenesis induced by 2 human
      tumors, MCF-7 breast carcinoma (estradiol dependent) and NIH-OVCAR-3 ovarian
      carcinoma (estradiol independent), was assessed. Treatment of nude mice bearing
      MCF-7 tumors with tamoxifen resulted in a 68% decrease in the number of vessels
      at the tumor periphery. Treatment with IFN-beta yielded a 33% reduction.
      Treatment of nude mice bearing NIH-OVCAR-3 tumors with tamoxifen resulted in a
      73% decrease in the number of vessels. Treatment with IFN-beta yielded a 57%
      reduction. Combination treatment resulted in augmented anti-angiogenic effects.
      As single agents, both tamoxifen and IFN-beta inhibited xenograft tumor growth.
      Ten weeks of tamoxifen treatment resulted in growth inhibition of MCF-7 and NIH
      OVCAR-3 carcinomas by 85% and 66%, respectively. Ten weeks of IFN-beta treatment
      resulted in inhibition of growth of MCF-7 and NIH-OVCAR-3 carcinomas by 67% and
      88%, respectively. The combination of tamoxifen and IFN-beta completely prevented
      growth of MCF-7 and NIH-OVCAR-3 carcinomas. The anti-angiogenic effects of
      tamoxifen and IFN-beta were additive. Inhibition of angiogenesis was detectable
      before measurable effects on tumor volume in both MCF-7 and NIH-OVCAR-3 tumors.
      Potentiation of anti-angiogenic effects by tamoxifen and IFN-beta, possibly
      resulting from enhanced IFN-induced gene expression, may contribute to anti-tumor
      activity in both estradiol-dependent and estradiol-independent tumors in vivo.

PMID- 9139885
TI  - Hyaluronan-independent lodgment of CD44+ lymphoma cells in lymphoid organs.
AB  - We previously found that monoclonal antibodies (MAbs) directed against the
      constant region of the CD44 molecule block lymph node infiltration of a mouse LB
      T-cell lymphoma, suggesting a role for this glycoprotein in the LB cell
      dissemination process. In the present study, we investigated whether LB cells in
      the local tumor must undergo a change in the CD44 phenotype to be able to migrate
      to and invade the remote lymph nodes, and if hyaluronic acid (HA), the principal
      ligand of activated CD44, functions as a mediator in this process. We compared
      the in vivo behavior of a non-HA-binder LB cell line with that of a constitutive
      HA-binder HA9 subline. Our results show that the lymphoid organ-infiltrating LB
      cells express similar levels of pan-CD44 and V4- and V6-containing CD44 variants,
      as the corresponding cells in the local growth and the cultured LB cells. The
      tested CD44 phenotype of HA9 cells also remained unchanged during the metastatic
      process. Even after lymph node infiltration, LB cells remained incapable of
      binding HA, whereas the HA9 cells retained an efficient HA-binding capacity. The
      constitutive HA-binder HA9 cells that expressed an approximately 10-fold higher
      level of pan-CD44 than did the parental LB cells, as well as an elevated level of
      the V4 and V6 exon products formed a local tumor and invaded both lymph nodes and
      spleen, as did the parental LB cells, albeit at a much slower rate. Our finding
      indicates that there is no direct correlation between the amount of CD44
      expressed on the cell surface, the HA-binding capacity and tumorigenicity.
      Moreover, interaction with HA is not obligatory for LB cell localization in the
      lymphoid organs, and a tight cell-HA interaction, as observed in HA9 cells, does
      not prevent tumor cell dissemination, although it may retard tumor spread.

PMID- 9139886
TI  - Tissue-specific expression of HSV-tk gene can induce efficient antitumor effect
      and protective immunity to wild-type hepatocellular carcinoma.
AB  - The efficacy of expression of the herpes simplex virus thymidine kinase (HSV-tk)
      gene under the transcriptional control of the liver-specific albumin gene
      promoter, followed by ganciclovir treatment, was investigated both in vitro and
      in vivo. Murine and rat hepatocellular carcinoma (HCC) cells infected with
      retroviruses carrying the HSV-tk gene under the control of the murine albumin
      gene promoter were selectively killed by ganciclovir treatment in vitro, whereas
      non-HCC cells, such as murine mammary tumor cells and fibroblast cells, which
      were infected with the same retroviruses, were not. Susceptibility of the
      retroviral-infected HCC cells to ganciclovir was more than 100-fold higher than
      that of the retroviral-infected non-HCC cells. When mice bearing a bulky HCC mass
      consisting of the retroviral-infected HCC cells were treated with systemic
      ganciclovir administration, complete regression of the tumors was observed
      without any signs of overt toxicity. Profound antitumor effects on preestablished
      murine HCCs were observed when wild-type HCC cells were implanted into animals
      with a small percentage of the retroviral-infected counterparts. When only 5% of
      the cells were infected with retroviruses carrying the HSV-tk gene, significant
      inhibition of tumor development was observed with systemic ganciclovir treatment.
      Importantly, animals that were treated with implantation of mixtures of the
      retroviral-infected and parental HCC cells, followed by ganciclovir
      administration, did not exhibit tumor formation and resisted subsequent
      rechallenge with wild-type HCC cells. Our results indicate the feasibility of
      combination therapy with the HSV-tk gene and ganciclovir for the treatment of
      HCC.

PMID- 9139887
TI  - Transfection of the gene for B7-1 but not B7-2 can induce immunity to murine
      malignant mesothelioma.
AB  - Transfection of the genes encoding the co-stimulatory molecules B7-1 and B7-2 has
      enhanced the development of immunity to a variety of experimental tumors,
      although most of these were inherently immunogenic. We have determined the effect
      of expression of these genes on the induction of immunity to 2 non-immunogenic
      murine malignant mesothelioma (MM) cell lines (AC29 and AB1). We had previously
      shown that B7-1 transfection into AC29 delayed but did not prevent tumor
      development by certain of the transfectant clones. Here we demonstrate that over
      expression of B7-1 can inhibit tumor development by certain AB1-B7-1 clones, that
      inhibition of transfectant growth is dependent on CD4+ and CD8+ T cells and that
      mice that reject some of these transfectant clones are capable of rejecting
      subsequent inocula of the parental cell line, AB1. The transfectant clones can
      generate tumor-specific cytotoxic T cells. By contrast, expression of B7-2 in
      several clones derived from either AB1 or AC29 had no significant effect on the
      development of tumors in vivo. Our data are consistent with data from other
      systems that show differences in the effect of modification by B7-1 or B7-2 on
      the modulation of anti-tumor immune responses. They demonstrate that such
      modifications can induce protective immunity against an MM cell line but confirm
      the intra- and inter-tumoral heterogeneity in the effect of genetic modification
      on the induction of immunity. Our observations are relevant to human MM because
      these cell lines have been derived from asbestos-induced tumors and share many
      properties with human cell lines of the same histological type.

PMID- 9139888
TI  - Expression of beta 1,6 branched asparagine-linked oligosaccharides in non-mitotic
      and non-migratory cells of normal human and rat tissues.
AB  - Malignant transformation of cells leads to the synthesis of large asparagine
      linked oligosaccharides that exhibit a higher degree of beta 1,6 branching. In
      rodent and human tumor cell lines and certain human tumors, increased beta 1,6
      branching of oligosaccharides has been shown to be associated with metastasis. In
      addition, this structural change occurs in glycoproteins of stimulated normal
      human lymphocytes. The leukoagglutinating Phaseolus vulgaris lectin (L-PHA) has a
      high affinity for tri- and tetraantennary beta 1,6 branches carrying
      oligosaccharides and has been widely used for the detection of such structures by
      histochemistry and blotting. We have analyzed a spectrum of normal human and rat
      tissues using a sensitive silver-intensified lectin-gold technique. Staining by L
      PHA was detected in undifferentiated cells of germinative layers of the
      gastrointestinal and respiratory tract as well as testis. However, differentiated
      and non-mitotic epithelia in most organs showed strong lectin staining as well.
      Notable exceptions were the epithelium of the colon and resting mammary gland,
      which were unreactive with L-PHA. The histochemical studies were supplemented by
      lectin blotting, which showed the presence of diverse L-PHA-reactive
      glycoproteins in rat tissues. Our data may be of importance for the use of L-PHA
      in studies on human malignant tumors.

PMID- 9139889
TI  - Generation of tumoricidal cytotoxic T lymphocytes from healthy donors after in
      vitro stimulation with a replication-incompetent vaccinia virus encoding MART
      1/Melan-A 27-35 epitope.
AB  - Active specific immunotherapy targeting tumor-associated antigens (TAA) requires
      reagents of high immunogenicity and safety. To address this issue, we constructed
      a recombinant vaccinia virus carrying a minigene insert encoding the HLA-A2.1
      restricted MART-1/Melan-A27-35 melanoma TAA (rVV-M). To facilitate the entry of
      the antigenic epitope into the endoplasmic reticulum, a sequence coding for
      adenovirus E3/19K leader peptide was added. This rVV-M was made replication
      incompetent by treatment with psoralen and UV light. Infection with rVV-M
      rendered HLA-A2.1 EBV-transformed lymphoblastoid cells sensitive to the cytotoxic
      effects of HLA-class-1-restricted, MART-1/Melan-A27-35-specific cytotoxic T
      lymphocytes (CTL). The capacity of rVV-M to generate HLA-A2.1-restricted MART
      1/Melan A-specific CTL was demonstrated from tumor-infiltrating-lymphocyte (TIL)
      cultures and from healthy donors' peripheral-blood mononuclear cells (PBMC). MART
      1/Melan-A27-35-specific CTL were generated from TIL after 2 weekly stimulation
      courses. Infection with rVV-M elicited a higher CTL response than addition of
      exogenous peptide, whereas, when a similar protocol was used to stimulate PBMC of
      healthy donors, significant and specific cytotoxic activity could be observed
      only upon rVV-M infection but not upon exogenous peptide addition. All CTL
      generated upon rVV-M stimulation were also able to efficiently kill melanoma cell
      lines expressing both MART-1/Melan-A and HLA-A2.1. In addition, TNF-alpha
      production could be induced in rVV-M-stimulated CTL upon co-culture with COS-7
      cells transiently transfected with MART-1/Melan-A and HLA-A2.1 genes. This safe
      and highly immunogenic reagent could be of use in TAA-targeted clinical
      immunotherapy.

PMID- 9139890
TI  - Activity of retinoic acid receptor-gamma selectively binding retinoids alone and
      in combination with interferon-gamma in breast cancer cell lines.
AB  - Retinoids modulate several cell functions and especially inhibit the growth of a
      wide variety of cells including breast cancer. Retinoic acid receptor-gamma (RAR
      gamma) has been shown to mediate the antiproliferative activity of retinoids. To
      further test this hypothesis we examined the effects of different RAR-gamma
      selectively binding retinoids (CD2325, CD2247, CD666 and CD437) on breast cancer
      cell lines. With exception of CD2247, all retinoids inhibited proliferation of
      MCF-7, SKBR-3, T47D and ZR-75-1 breast cancer cell lines, similar to the natural
      compound all-trans retinoic acid (ATRA). In addition, all 4 compounds were able
      to act synergistically with interferon-gamma (IFN-gamma) in all breast cancer
      cell lines including the retinoid-resistant BT-20 and 734-B lines. In functional
      transactivation assays we demonstrated that only in the MCF-7 cell line, TPA
      mediated AP-1 activity was suppressed only by ATRA and CD2325, whereas in SKBR-3,
      another RA-sensitive breast cancer cell line, it was not. The synergistic
      antiproliferative activity involving retinoids and IFN-gamma could not be
      explained by an enhanced anti-AP-1 activity. No correlation was found between
      expression of RARs and cellular retinoic acid binding proteins (CRABPs) and
      antiproliferative effects of the retinoids. RAR-gamma selectively binding
      retinoids are potent inhibitors of breast cancer cell proliferation, alone and in
      combination with IFN-gamma. For this reason and because of a possible low
      toxicity, as compared with retinoic acid, we speculate that these RAR-gamma
      selective binding retinoids might be of clinical importance.

PMID- 9139891
TI  - Phylogenetic relationships of Bacillus thuringiensis delta-endotoxin family
      proteins and their functional domains.

PMID- 9139892
TI  - A divergently transcribed open reading frame is located upstream of the
      Pseudomonas aeruginosa vfr gene, a homolog of Escherichia coli crp.
AB  - The Pseudomonas aeruginosa homolog of the Escherichia coli global transcriptional
      regulator CRP (or CAP) was recently identified and designated Vfr (S. E. H. West,
      A. K. Sample, and L. J. Runyen-Janecky, J. Bacteriol. 176:7532-7542, 1994).
      Nucleotide sequence analysis of the region 5' to vfr identified a 423-bp open
      reading frame (ORF), which was designated orfX. The deduced amino acid sequence
      of ORFX was 53% identical and 87% similar to a divergent ORF of unknown function
      located 5' to the E. coli crp gene. When orfX was expressed from a phage T7
      promoter in E. coli, a protein with an apparent molecular mass of approximately
      18 kDa was produced. We constructed a chromosomal deletion of the region
      containing the 5' end of orfX (orfX'), vfr, and the 3' end of trpC (trpC') in P.
      aeruginosa strains PAO1 and PA103. The cloned vfr gene restored Vfr-dependent
      production of exotoxin A and protease in the PA103 orfX'-vfr-trpC' deletion
      mutant, suggesting that ORFX is not required for Vfr production or activity. To
      determine whether transcription of orfX and vfr are controlled by the same
      mechanisms that control transcription of the region of the divergent ORF (dorf)
      and of crp, we compared the vfr-orfX and crp-dorf intergenic regions. Using S1
      nuclease analysis, we determined that the distance between the orfX and vfr
      transcriptional start sites was 105 bp. Thus, the P. aeruginosa orfX and vfr
      promoters are arranged in a back-to-back orientation rather than the face-to-face
      orientation of the dorf and crp promoters. A CRP recognition site is associated
      with each promoter in the crp-dorf intergenic region; binding of the CRP-cyclic
      AMP complex to the stronger dorf CRP recognition site activates transcription
      from the dorf promoter and represses transcription from the crp promoter. The vfr
      orfX intergenic region does not contain an obvious CRP recognition site. In
      addition, vfr was not required for transcription of orfX. Unlike the dorf and crp
      mRNAs, the 5' ends of the orfX and vfr mRNAs were not complementary. Thus, the
      orfX mRNA cannot hybridize to the 5' end of the vfr mRNA to inhibit vfr
      transcription, a mechanism that has been postulated to control crp transcription
      in E. coli.

PMID- 9139893
TI  - Role of scaffolding protein CipC of Clostridium cellulolyticum in cellulose
      degradation.
AB  - The role of a miniscaffolding protein, miniCipC1, forming part of Clostridium
      cellulolyticum scaffolding protein CipC in insoluble cellulose degradation was
      investigated. The parameters of the binding of miniCipC1, which contains a family
      III cellulose-binding domain (CBD), a hydrophilic domain, and a cohesin domain,
      to four insoluble celluloses were determined. At saturating concentrations, about
      8.2 micromol of protein was bound per g of bacterial microcrystalline cellulose,
      while Avicel, colloidal Avicel, and phosphoric acid-swollen cellulose bound 0.28,
      0.38, and 0.55 micromol of miniCipC1 per g, respectively. The dissociation
      constants measured varied between 1.3 x 10(-7) and 1.5 x 10(-8) M. These results
      are discussed with regard to the properties of the various substrates. The
      synergistic action of miniCipC1 and two forms of endoglucanase CelA (with and
      without the dockerin domain [CelA2 and CelA3, respectively]) in cellulose
      degradation was also studied. Although only CelA2 interacted with miniCipC1
      (K(d), 7 x 10(-9) M), nonhydrolytic miniCipC1 enhanced the activities of
      endoglucanases CelA2 and CelA3 with all of the insoluble substrates tested. This
      finding shows that miniCipC1 plays two roles: it increases the enzyme
      concentration on the cellulose surface and enhances the accessibility of the
      enzyme to the substrate by modifying the structure of the cellulose, leading to
      an increased available cellulose surface area. In addition, the data obtained
      with a hybrid protein, CelA3-CBD(CipC), which was more active towards all of the
      insoluble substrates tested confirm that the CBD of the scaffolding protein plays
      an essential role in cellulose degradation.

PMID- 9139894
TI  - Cnr protein, the negative regulator of bacteriophage P4 replication, stimulates
      specific DNA binding of its initiator protein alpha.
AB  - Bacteriophage P4 DNA replication depends upon the phage-encoded alpha protein,
      which has DNA helicase and DNA primase activity and can specifically bind to the
      replication origin (ori) and to the cis replicating region (crr). The P4 Cnr
      protein functions as a negative regulator of P4 replication, and P4 does not
      replicate in cells that overexpress cnr. We searched for P4 mutants that
      suppressed this phenotype (Cnr resistant [alpha cr]). Eight independent mutants
      that grew in the presence of high levels of Cnr were obtained. None of these can
      establish the plasmid state. Each of these mutations lies in the DNA binding
      domain of gp alpha that occupies the C terminus of the protein. Five different
      sequence changes were found: T675M, G732V (three times), G732W (twice), L733V,
      and L737V. A TrxA-Cnr fusion protein does not bind DNA by itself but stimulates
      the ori and crr binding abilities of alpha protein in vitro. The alpha cr mutant
      proteins were still able to bind specifically to ori or crr, but specific DNA
      binding was less stimulated by the TrxA-Cnr protein. We present evidence that Cnr
      protein interacts with the gp alpha domain that binds specifically to DNA and
      that gp(alpha)cr mutations impair this interaction. We hypothesize that gp alpha
      Cnr interaction is essential for the control of P4 DNA replication.

PMID- 9139895
TI  - Murein segregation in Escherichia coli.
AB  - Peptidoglycan (murein) segregation has been studied by means of a new labeling
      method. The method relies on the ability of Escherichia coli cells to incorporate
      D-Cys into macromolecular murein. The incorporation depends on a periplasmic
      amino acid exchange reaction. At low concentrations, D-Cys is innocuous to the
      cell. The distribution of modified murein in purified sacculi can be traced and
      visualized by immunodetection of the -SH groups by fluorescence and electron
      microscopy techniques. Analysis of murein segregation in wild-type and cell
      division mutant strains revealed that murein in polar caps is metabolically inert
      and is segregated in a conservative fashion. Elongation of the sacculus
      apparently occurs by diffuse insertion of precursors over the cylindrical part of
      the cell surface. At the initiation of cell division, there is a FtsZ-dependent
      localized activation of murein synthesis at the potential division sites.
      Penicillin-binding protein 3 and the products of the division genes ftsA and ftsQ
      are dispensable for the activation of division sites. As a consequence, under
      restrictive conditions ftsA,ftsI,or ftsQ mutants generate filamentous sacculi
      with rings of all-new murein at the positions where septa would otherwise
      develop.

PMID- 9139896
TI  - Mutagenic properties of the T-C cyclobutane dimer.
AB  - G x C-->A x T transitions within T-C or C-C bipyrimidine sequences are by far the
      most frequent class of mutation induced by 254-nm UV irradiation in most genes
      and species investigated, but the reason for the high degree of mutability and
      specificity at these sites is uncertain. Some data implicate the deamination of
      cytosine to uracil as a possible cause, but other results appear to indicate that
      the rate of deamination is too low for this to be significant in Escherichia
      coli. If deamination is not the cause, the high degree of mutability must
      presumably reflect the inherent properties of T-C and C-C dimers. We investigated
      this question by transfecting excision-deficient and excision-proficient strains
      of E. coli with single-stranded vectors that carried a site-specific cis-syn T-C
      cyclobutane dimer and by analyzing the nucleotide sequences of replicated vector
      products. We found that replication past the T-C dimer, like replication past its
      T-T and U-U counterparts, is in fact >95% accurate and that the frequencies of
      bypass are also very similar for these photoproducts. Since the T-C dimer appears
      to be only weakly mutagenic, the high frequency of UV-induced mutations at T-C
      sites presumably depends on some other process, such as deamination, although the
      mechanism remains to be established.

PMID- 9139897
TI  - The A protein of the filamentous bacteriophage Cf of Xanthomonas campestris pv.
      citri.
AB  - Filamentous bacteriophages have very strict host specificities. Experiments were
      performed to investigate whether the A protein of the filamentous phage Cf, which
      infects Xanthomonas campestris pv. citri but not X. campestris pv. oryzae, is
      involved in determining Cf's host specificity. The gene encoding the A protein of
      Cf was cloned and expressed in X. campestris pv. citri. The genomic DNA of
      another filamentous bacteriophage, Xf, which infects X. campestris pv. oryzae but
      not X. campestris pv. citri, was then introduced by electroporation into X.
      campestris pv. citri that had expressed the A protein of Cf. The progeny phages
      thus produced were able to infect both X. campestris pv. oryzae and X. campestris
      pv. citri, indicating that the A protein of Cf was incorporated into the viral
      particles of Xf and conferred upon Xf the ability to infect the host of Cf.
      Inactivation of the A protein gene abolished the infectivity of Cf. The results
      of this study indicate that the A protein of Cf is responsible for controlling
      the host specificity of Cf.

PMID- 9139898
TI  - Three Bacillus cereus bacteriophage endolysins are unrelated but reveal high
      homology to cell wall hydrolases from different bacilli.
AB  - The ply genes encoding the endolysin proteins from Bacillus cereus phages
      Bastille, TP21, and 12826 were identified, cloned, and sequenced. The endolysins
      could be overproduced in Escherichia coli (up to 20% of total cellular protein),
      and the recombinant proteins were purified by a two-step chromatographical
      procedure. All three enzymes induced rapid and specific lysis of viable cells of
      several Bacillus species, with highest activity on B. cereus and B.
      thuringiensis. Ply12 and Ply21 were experimentally shown to be N-acetylmuramoyl-L
      alanine amidases (EC 3.5.1.28). No apparent holin genes were found adjacent to
      the ply genes. However, Ply21 may be endowed with a signal peptide which could
      play a role in timing of cell lysis by the cytoplasmic phage endolysin. The
      individual lytic enzymes (PlyBa, 41.1 kDa; Ply21, 29.5 kDa, Ply12, 27.7 kDa) show
      remarkable heterogeneity, i.e., their amino acid sequences reveal only little
      homology. The N-terminal part of Ply21 was found to be almost identical to the
      catalytic domains of a Bacillus sp. cell wall hydrolase (CwlSP) and an autolysin
      of B. subtilis (CwlA). The C terminus of PlyBa contains a 77-amino-acid sequence
      repeat which is also homologous to the binding domain of CwlSP. Ply12 shows
      homology to the major autolysins from B. subtilis and E. coli. Comparison with
      database sequences indicated a modular organization of the phage lysis proteins
      where the enzymatic activity is located in the N-terminal region and the C
      termini are responsible for specific recognition and binding of Bacillus
      peptidoglycan. We speculate that the close relationship of the phage enzymes and
      cell wall autolysins is based upon horizontal gene transfer among different
      Bacillus phages and their hosts.

PMID- 9139899
TI  - High-level genetic diversity in the vapD chromosomal region of Helicobacter
      pylori.
AB  - Helicobacter pylori isolates from different patients are characterized by
      diversity in the nucleotide sequences of individual genes, variation in genome
      size, and variation in gene order. Genetic diversity is particularly striking in
      vacuolating cytotoxin (vacA) alleles. In this study, five open reading frames
      (ORFs) were identified within a 4.2-kb region downstream from vacA in H. pylori
      60190. One of these ORFs was closely related to the virulence-associated protein
      D (vapD) gene of Dichelobacter nodosus (64.9% nucleotide identity). A probe
      derived from vapD of H. pylori 60190 hybridized with only 19 (61.3%) of 31 H.
      pylori strains tested. Sequence analysis of the vapD region in vapD-negative H.
      pylori strains revealed that there were two different families of approximately
      0.5-kb DNA segments, which were both unrelated to vapD. The presence of vapD was
      not associated with any specific family of vacA alleles. These findings are
      consistent with a recombinational population structure for H. pylori.

PMID- 9139900
TI  - Lethality of the covalent linkage between mislocalized major outer membrane
      lipoprotein and the peptidoglycan of Escherichia coli.
AB  - The major outer membrane lipoprotein (Lpp) of Escherichia coli possesses serine
      at position 2, which is thought to function as the outer membrane sorting signal,
      and lysine at the C terminus, through which Lpp covalently associates with
      peptidoglycan. Arginine (R) is present before the C-terminal lysine in the wild
      type Lpp (LppSK). By replacing serine (S) at position 2 with aspartate (D), the
      putative inner membrane sorting signal, and by deleting lysine (K) at the C
      terminus, Lpp mutants with a different residue at either position 2 (LppDK) or
      the C terminus (LppSR) or both (LppDR) were constructed. Expression of LppSR and
      LppDR little affected the growth of E. coli. In contrast, the number of viable
      cells immediately decreased when LppDK was expressed. Prolonged expression of
      LppDK inhibited separation of the inner and outer membranes by sucrose density
      gradient centrifugation, whereas short-term expression did not. Pulse-labeled
      LppDK and LppDR were localized in the inner membrane, indicating that the amino
      acid residue at position 2 functions as a sorting signal for the membrane
      localization of Lpp. LppDK accumulated in the inner membrane covalently
      associated with the peptidoglycan and thus prevented the separation of the two
      membranes. Globomycin, an inhibitor of lipoprotein-specific signal peptidase II,
      was lethal for E. coli only when Lpp possessed the C-terminal lysine. Taken
      together, these results indicate that the inner membrane accumulation of Lpp per
      se is not lethal for E. coli. Instead, a covalent linkage between the inner
      membrane Lpp having the C-terminal lysine and the peptidoglycan is lethal for E.
      coli, presumably due to the disruption of the cell surface integrity.

PMID- 9139901
TI  - Identification and characterization of Myxococcus xanthus mutants deficient in
      calcofluor white binding.
AB  - Calcofluor white is a fluorescent dye that binds to glycans and can be used to
      detect extracellular polysaccharide in Myxococcus xanthus and many other
      bacteria. We observed that an esg mutant showed less binding to calcofluor white
      than wild-type cells. Unlike S-motility mutants that share this phenotypic
      characteristic, the esg mutant exhibited S motility. This led us to identify a
      collection of nine new transposon insertion mutants, designated Cds (for
      calcofluor white binding deficient and S motile), which exhibited a phenotype
      similar to that of the esg strain. The Cds phenotype was found in 0.6% of the
      random insertion mutants that were screened. The Cds mutants were also found to
      be defective in cell-cell agglutination and developmental aggregation.
      Extracellular matrix fibrils composed of roughly equal amounts of polysaccharide
      and protein have been shown to be involved in agglutination, and electron
      microscopic examination showed that esg and the other Cds mutants lack the wild
      type level of fibrils. Analysis of total M. xanthus carbohydrate demonstrated
      that polysaccharide content increased by about 50% when wild-type cells entered
      stationary phase. This induction was reduced or eliminated in all of the Cds
      mutants. The degree of polysaccharide deficiency in the Cds mutants correlated
      with the degree of loss of agglutination and dye binding as well as with the
      severity of the developmental aggregation defect. Preliminary genetic
      characterization demonstrated that the transposon insertion mutations in three of
      the Cds mutants (SR53, SR171, and SR200) were loosely linked. The results of this
      study suggest that many genes are involved in the production of calcofluor white
      binding polysaccharide material found in the extracellular matrix and that the
      polysaccharide is fibrillar. These results are also consistent with the findings
      of earlier studies which indicated that fibrils function to join agglutinating
      cells and to form multicellular fruiting aggregates.

PMID- 9139903
TI  - Effect of lipoteichoic acid on thermotropic membrane properties.
AB  - Lipoteichoic acid, diglucosyldiacylglycerol, and phosphatidylglycerol isolated
      from Staphylococcus aureus were embedded in dipalmitoylglycerophosphoglycerol
      vesicles, and their thermotropic influence on this matrix was studied by
      differential scanning calorimetry. The natural fatty acids of
      phosphatidylglycerol effected peak broadening and a decrease in molar heat
      capacity. These effects were more pronounced with the glycolipid, which also
      increased the main transition temperature. With the lipoteichoic acid mixtures,
      two broad main transition peaks were observed, possibly due to different levels
      of lipoteichoic acid in vesicles. Both peaks showed a further upshift in
      transition temperatures and a pronounced decrease in molar heat capacity. Since
      the diacylglycerol moieties of all three amphiphiles were practically identical,
      the differences in the thermotropic effects have to be ascribed to the different
      structures of the head groups. Diglucosyldiacylglycerol is proposed to exert an
      additional effect by hydrogen bonding the hydroxyls of the sugar rings to their
      phospholipid neighbors. The stronger effect of lipoteichoic acid points to
      dynamic interactions of the long hydrophilic chain with the vesicle surface,
      which stabilize the membrane structure.

PMID- 9139902
TI  - Unbalanced membrane phospholipid compositions affect transcriptional expression
      of certain regulatory genes in Escherichia coli.
AB  - The amount of porin protein OmpF in the outer membrane of Escherichia coli was
      reduced to one-third by the pgsA3 mutation that diminishes the amount of
      phosphatidylglycerol and cardiolipin in the membrane, whereas a cls (cardiolipin
      synthase) null mutation had no effect. Osmoregulation of OmpF was functional in
      the pgsA3 mutant. As assessed by the beta-galactosidase activities of lacZ
      fusions, the ompF expression was not reduced at the transcriptional level but was
      reduced about threefold at the posttranscriptional level by pgsA3. This reduction
      was mostly restored by a micF null mutation, and the micF RNA that inhibits the
      ompF mRNA translation was present 1.3 to 1.4 times more in the pgsA3 mutant, as
      assayed by RNase protection and Northern blot analyses. Elevation of the level of
      micF RNA was not restricted to acidic-phospholipid deficiency: OmpF was hardly
      detected and micF RNA was present 2.7 to 2.8 times more in a pssA null mutant
      that lacked phosphatidylethanolamine. Other common phenotypes of pgsA3 and pssA
      null mutants, reduced rates of cell growth and phospholipid synthesis, were not
      the cause of micF activation. Salicylate, which activates micF expression and
      inhibits cell motility, did not repress the flagellar master operon. These
      results imply that an unbalanced phospholipid composition, rather than a decrease
      or increase in the amount of specific phospholipid species, induces a
      phospholipid-specific stress signal to which certain regulatory genes respond
      positively or negatively according to their intrinsic mechanisms.

PMID- 9139904
TI  - Lipopolysaccharide dependence of cyanophage sensitivity and aerobic nitrogen
      fixation in Anabaena sp. strain PCC 7120.
AB  - Fox- mutants of Anabaena sp. strain PCC 7120 are unable to fix dinitrogen in the
      presence of oxygen. A fragment of the DNA of Anabaena sp. was cloned by
      complementation of a spontaneous Fox-, cyanophage-resistant mutant, R56, and
      characterized. Random insertion of transposon Tn5 delimited the complementing DNA
      to a 0.6-kb portion of the cloned fragment. Sequencing of this region and
      flanking DNA showed one complete open reading frame (ORF) similar to the gene
      rfbP (undecaprenyl-phosphate galactosephosphotransferase) and two partial ORFs
      similar to genes rfbD (GDP-D-mannose dehydratase) and rfbZ (first mannosyl
      transferase), all of which are active in the synthesis of the O antigen unit of
      the lipopolysaccharide (LPS) component of the outer membrane of gram-negative
      bacteria. In a transposon (Tn5-1087b)-induced, Fox-, cyanophage-resistant mutant,
      B14, the transposon was found within the same rfbP-like ORF. The three ORFs were
      insertionally inactivated with the omega cassette (P. Prentki and H. M. Krisch,
      Gene 29:303-313, 1984) or with Tn5::omega. Only the insertions in the rfbZ- and
      rfbP-like ORFs led to resistance to cyanophages A-1(L) and A-4(L) and to a Fox-
      phenotype. Electrophoretic analysis showed that interruption of the rfbZ- and
      rfbP-like ORFs resulted in a change in or loss of the characteristic pattern of
      the lengths of the LPS, whereas interruption of the rfbD-like ORF merely changed
      the distribution of the lengths of the LPS to one with a greater prevalence of
      low molecular weights. According to electron microscopy, interruption of the rfbP
      like ORF may have led to aberrant deposition of the layers of the heterocyst
      envelope, resulting in increased leakage of oxygen into the heterocyst. The
      results suggest that modified LPS may prevent cyanophage infection of Anabaena
      sp. vegetative cells and the formation of a functional heterocyst envelope.

PMID- 9139905
TI  - Identification and characterization of ssb and uup mutants with increased
      frequency of precise excision of transposon Tn10 derivatives: nucleotide sequence
      of uup in Escherichia coli.
AB  - A Lac+ papillation assay was used to identify mutants (tex) of Escherichia coli
      that exhibit an increased frequency of precise excision of a lacZ::Tn10dKan
      insertion. Three tex strains had suffered mutations in the gene (ssb) encoding
      the essential single-stranded DNA-binding protein SSB, which resulted in the
      following alterations in the 177-residue protein: G4D; L10F, P24S; and V102M. The
      phenotypes of these ssb mutants indicated that they were largely unaffected in
      other functions mediated by SSB, such as DNA replication, recombination, and
      repair. Strains with multicopy ssb+ exhibited a decreased frequency of Tn10dKan
      precise excision. Three other tex mutants had insertion mutations in the locus
      designated uup at 21.75 min on the linkage map. The nucleotide sequence of uup
      was determined, and the gene was inferred to encode a 625-amino-acid hydrophilic
      protein that belongs to the superfamily of ABC-domain proteins (with two pairs of
      the Walker A and B motifs), which are postulated to be involved in coupling ATP
      hydrolysis with other biological processes. The uup gene product shares extensive
      homology with the deduced sequences of two proteins of Haemophilus influenzae.
      The uup gene is also situated immediately upstream of (and is transcribed in the
      same direction as) the paraquat-inducible SoxRS-regulated pqi-5 gene, two
      reported promoters for which are situated within the uup coding sequence.

PMID- 9139906
TI  - Three different putative phosphate transport receptors are encoded by the
      Mycobacterium tuberculosis genome and are present at the surface of Mycobacterium
      bovis BCG.
AB  - A gene encoding a protein homologous to the periplasmic ABC phosphate binding
      receptor PstS from Escherichia coli was cloned and sequenced from a lambda gt11
      library of Mycobacterium tuberculosis by screening with monoclonal antibody 2A1
      2. Its degree of similarity to the E. coli PstS is comparable to those of the
      previously described M. tuberculosis phosphate binding protein pab (Ag78, Ag5, or
      38-kDa protein) and another M. tuberculosis protein which we identified recently.
      We suggest that the three M. tuberculosis proteins share a similar function and
      could be named PstS-1, PstS-2, and PstS-3, respectively. Molecular modeling of
      their three-dimensional structures using the structure of the E. coli PstS as a
      template and their inducibility by phosphate starvation support this view.
      Recombinant PstS-2 and PstS-3 were produced and purified by affinity
      chromatography. With PstS-1, these proteins were used to demonstrate the
      specificity of three groups of monoclonal antibodies. Using these antibodies in
      flow cytometry and immunoblotting analyses, we demonstrate that the three genes
      are expressed and their protein products are present and accessible at the
      mycobacterial surface as well as in its culture filtrate. Together with the M.
      tuberculosis genes encoding homologs of the PstA, PstB, and PstC components we
      cloned before, the present data suggest that at least one, and possibly several,
      related and functional ABC phosphate transporters exist in mycobacteria. It is
      hypothesized that the mycobacterial gene duplications presented here may be a
      subtle adaptation of intracellular pathogens to phosphate starvation in their
      alternating growth environments.

PMID- 9139907
TI  - Regulation of heme biosynthesis in Salmonella typhimurium: activity of glutamyl
      tRNA reductase (HemA) is greatly elevated during heme limitation by a mechanism
      which increases abundance of the protein.
AB  - In Salmonella typhimurium and Escherichia coli, the hemA gene encodes the enzyme
      glutamyl-tRNA reductase, which catalyzes the first committed step in heme
      biosynthesis. We report that when heme limitation is imposed on cultures of S.
      typhimurium, glutamyl-tRNA reductase (HemA) enzyme activity is increased 10- to
      25-fold. Heme limitation was achieved by a complete starvation for heme in hemB,
      hemE, and hemH mutants or during exponential growth of a hemL mutant in the
      absence of heme supplementation. Equivalent results were obtained by both
      methods. To determine the basis for this induction, we developed a panel of
      monoclonal antibodies reactive with HemA, which can detect the small amount of
      protein present in a wild-type strain. Western blot (immunoblot) analysis with
      these antibodies reveals that the increase in HemA enzyme activity during heme
      limitation is mediated by an increase in the abundance of the HemA protein.
      Increased HemA protein levels were also observed in heme-limited cells of a hemL
      mutant in two different E. coli backgrounds, suggesting that the observed
      regulation is conserved between E. coli and S. typhimurium. In S. typhimurium,
      the increase in HemA enzyme and protein levels was accompanied by a minimal (less
      than twofold) increase in the expression of hemA-lac operon fusions; thus HemA
      regulation is mediated either at a posttranscriptional step or through modulation
      of protein stability.

PMID- 9139908
TI  - The Bacillus subtilis sigma(X) protein is an extracytoplasmic function sigma
      factor contributing to survival at high temperature.
AB  - The sigX gene, identified as part of the international effort to sequence the
      Bacillus subtilis genome, has been proposed to encode an alternative sigma factor
      of the extracytoplasmic function (ECF) subfamily. The sigX gene is cotranscribed
      with a downstream gene, ypuN, during logarithmic and early stationary phases of
      growth. We now report that strains lacking sigma(X) are impaired in the ability
      to survive at high temperature whereas a ypuN mutant has increased
      thermotolerance. We overproduced and purified sigma(X) from Escherichia coli and
      demonstrate that in vitro, both sigma(A) and sigma(X) holoenzymes recognize
      promoter elements within the sigX-ypuN control region. However, they have
      distinct salt optima such that sigma(A)-dependent transcription predominates at
      low salt while sigma(X)-dependent transcription predominates at high salt. A 54
      bp region upstream of sigX suffices as a sigma(X)-dependent promoter in vivo,
      demonstrating that sigX is at least partially under positive autoregulatory
      control. Mutation of ypuN increases expression from the sigma(X)-dependent
      promoter in vivo, suggesting that ypuN may encode a negative regulator of
      sigma(X) activity.

PMID- 9139909
TI  - A mycobacterial extracytoplasmic function sigma factor involved in survival
      following stress.
AB  - The extracytoplasmic function (ECF) sigma factors constitute a diverse group of
      alternative sigma factors that have been demonstrated to regulate gene expression
      in response to environmental conditions in several bacterial species. Genes
      encoding an ECF sigma factor of Mycobacterium tuberculosis, Mycobacterium avium,
      and Mycobacterium smegmatis, designated sigE, were cloned and analyzed. Southern
      blot analysis demonstrated the presence of a single copy of this gene in these
      species and in Mycobacterium bovis BCG, Mycobacterium leprae, and Mycobacterium
      fortuitum. Sequence analysis showed the sigE gene to be highly conserved among M.
      tuberculosis, M. avium, M. smegmatis, and M. leprae. Recombinant M. tuberculosis
      SigE, when combined with core RNA polymerase from M. smegmatis, reconstituted
      specific RNA polymerase activity on sigE in vitro, demonstrating that this gene
      encodes a functional sigma factor. Two in vivo transcription start sites for sigE
      were also identified in M. smegmatis and M. bovis BCG. Comparison of wild-type M.
      smegmatis with a sigE mutant strain demonstrated decreased survival of the mutant
      under conditions of high-temperature heat shock, acidic pH, exposure to
      detergent, and oxidative stress. An inducible protective response to oxidative
      stress present in the wild type was absent in the mutant. The mycobacterial SigE
      protein, although nonessential for viability in vitro, appears to play a role in
      the ability of these organisms to withstand a variety of stresses.

PMID- 9139910
TI  - Identification and characterization of the nifV-nifZ-nifT gene region from the
      filamentous cyanobacterium Anabaena sp. strain PCC 7120.
AB  - The nifV and leuA genes, which encode homocitrate synthase and alpha
      isopropylmalate synthase, respectively, were cloned from the filamentous
      cyanobacterium Anabaena sp. strain PCC 7120 by a PCR-based strategy. Since the N
      terminal parts of NifV and LeuA from other bacteria are highly similar to each
      other, a single pair of PCR primers was used to amplify internal fragments of
      both Anabaena strain 7120 genes. Sequence analysis of cloned PCR products
      confirmed the presence of two different nifV-like DNA fragments, which were
      subsequently used as nifV- and leuA-specific probes, respectively, to clone XbaI
      fragments of 2.1 kbp (pOST4) and 2.6 kbp (pOST2). Plasmid pOST4 carried the
      Anabaena strain 7120 nifV-nifZ-nifT genes, whereas pOST2 contained the leuA and
      dapF genes. The nifVZT genes were not located in close proximity to the main nif
      gene cluster in Anabaena strain 7120, and therefore nifVZT forms a second nif
      gene cluster in this strain. Overlaps between the nifV and nifZ genes and between
      the nifZ and nifT genes and the presence of a 1.8-kb transcript indicated that
      nifVZT might form one transcriptional unit. Transcripts of nifV were induced not
      only in a nitrogen-depleted culture but also by iron depletion irrespective of
      the nitrogen status. The nifV gene in Anabaena strain 7120 was interrupted by an
      interposon insertion (mutant strain BMB105) and by a plasmid integration via a
      single crossover with a nifV internal fragment as a site for recombination
      (mutant strain BMB106). Both mutant strains were capable of diazotrophic growth,
      and their growth rates were only slightly impaired compared to that of the wild
      type. Heterologous complementation of the Rhodobacter capsulatus nifV mutant
      R229I by the Anabaena strain 7120 nifV gene corroborated the assumption that
      Anabaena strain 7120 nifV also encodes a homocitrate synthase. In contrast, the
      Anabaena strain 7120 leuA gene did not complement the nifV mutation of R229I
      efficiently.

PMID- 9139911
TI  - Biosynthesis of riboflavin: an unusual riboflavin synthase of Methanobacterium
      thermoautotrophicum.
AB  - Riboflavin synthase was purified by a factor of about 1,500 from cell extract of
      Methanobacterium thermoautotrophicum. The enzyme had a specific activity of about
      2,700 nmol mg(-1) h(-1) at 65 degrees C, which is relatively low compared to
      those of riboflavin synthases of eubacteria and yeast. Amino acid sequences
      obtained after proteolytic cleavage had no similarity with known riboflavin
      synthases. The gene coding for riboflavin synthase (designated ribC) was
      subsequently cloned by marker rescue with a ribC mutant of Escherichia coli. The
      ribC gene of M. thermoautotrophicum specifies a protein of 153 amino acid
      residues. The predicted amino acid sequence agrees with the information gleaned
      from Edman degradation of the isolated protein and shows 67% identity with the
      sequence predicted for the unannotated reading frame MJ1184 of Methanococcus
      jannaschii. The ribC gene is adjacent to a cluster of four genes with similarity
      to the genes cbiMNQO of Salmonella typhimurium, which form part of the cob operon
      (this operon contains most of the genes involved in the biosynthesis of vitamin
      B12). The amino acid sequence predicted by the ribC gene of M.
      thermoautotrophicum shows no similarity whatsoever to the sequences of riboflavin
      synthases of eubacteria and yeast. Most notably, the M. thermoautotrophicum
      protein does not show the internal sequence homology characteristic of
      eubacterial and yeast riboflavin synthases. The protein of M. thermoautotrophicum
      can be expressed efficiently in a recombinant E. coli strain. The specific
      activity of the purified, recombinant protein is 1,900 nmol mg(-1) h(-1) at 65
      degrees C. In contrast to riboflavin synthases from eubacteria and fungi, the
      methanobacterial enzyme has an absolute requirement for magnesium ions. The 5'
      phosphate of 6,7-dimethyl-8-ribityllumazine does not act as a substrate. The
      findings suggest that riboflavin synthase has evolved independently in eubacteria
      and methanobacteria.

PMID- 9139912
TI  - Roles of histidine-103 and tyrosine-235 in the function of the prolipoprotein
      diacylglyceryl transferase of Escherichia coli.
AB  - Phosphatidylglycerol:prolipoprotein diacylglyceryl transferase (Lgt) is the first
      enzyme in the posttranslational sequence of reactions resulting in the lipid
      modification of lipoproteins in bacteria. A previous comparison of the primary
      sequences of the Lgt enzymes from phylogenetically distant bacterial species
      revealed several highly conserved amino acid sequences throughout the molecule;
      the most extensive of these was the region 103HGGLIG108 in the Escherichia coli
      Lgt (H.-Y. Qi, K. Sankaran, K. Gan, and H. C. Wu, J. Bacteriol. 177:6820-6824,
      1995). These studies also revealed that the kinetics of inactivation of E. coli
      Lgt with diethylpyrocarbonate were consistent with the modification of a single
      essential histidine or tyrosine residue. The current study was conducted in an
      attempt to identify this essential amino acid residue in order to further define
      structure-function relationships in Lgt. Accordingly, all of the histidine
      residues and seven of the tyrosine residues of E. coli Lgt were altered by site
      directed mutagenesis, and the in vitro activities of the altered enzymes, as well
      the abilities of the respective mutant lgt alleles to complement the temperature
      sensitive phenotype of E. coli SK634 defective in Lgt activity, were determined.
      The data obtained from these studies, in conjunction with additional chemical
      inactivation studies, support the conclusion that His-103 is essential for Lgt
      activity. These studies also indicated that Tyr-235 plays an important role in
      the function of this enzyme. Although other histidine and tyrosine residues were
      not found to be essential for Lgt activity, alterations of His-196 resulted in a
      significant reduction of in vitro activity.

PMID- 9139913
TI  - Molecular characterization of a genomic region in a Lactococcus bacteriophage
      that is involved in its sensitivity to the phage defense mechanism AbiA.
AB  - A spontaneous mutant of the lactococcal phage phi31 that is insensitive to the
      phage defense mechanism AbiA was characterized in an effort to identify the phage
      factor(s) involved in sensitivity of phi31 to AbiA. A point mutation was
      localized in the genome of the AbiA-insensitive phage (phi31A) by heteroduplex
      analysis of a 9-kb region. The mutation (G to T) was within a 738-bp open reading
      frame (ORF245) and resulted in an arginine-to-leucine change in the predicted
      amino acid sequence of the protein. The mutant phi31A-ORF245 reduced the
      sensitivity of phi31 to AbiA when present in trans, indicating that the mutation
      in ORF245 is responsible for the AbiA insensitivity of phi31A. Transcription of
      ORF245 occurs early in the phage infection cycles of phi31 and phi31A and is
      unaffected by AbiA. Expansion of the phi31 sequence revealed ORF169 (immediately
      upstream of ORF245) and ORF71 (which ends 84 bp upstream of ORF169). Two inverted
      repeats lie within the 84-bp region between ORF71 and ORF169. Sequence analysis
      of an independently isolated AbiA-insensitive phage, phi31B, identified a
      mutation (G to A) in one of the inverted repeats. A 118-bp fragment from phi31,
      encompassing the 84-bp region between ORF71 and ORF169, eliminates AbiA activity
      against phi31 when present in trans, establishing a relationship between AbiA and
      this fragment. The study of this region of phage phi31 has identified an open
      reading frame (ORF245) and a 118-bp DNA fragment that interact with AbiA and are
      likely to be involved in the sensitivity of this phage to AbiA.

PMID- 9139914
TI  - Localized perforation of the cell wall by a major autolysin: atl gene products
      and the onset of penicillin-induced lysis of Staphylococcus aureus.
AB  - We investigated the cell surface localization of the atl gene products of
      Staphylococcus aureus exposed to a lytic concentration (4 MIC) of penicillin G
      (PCG) by means of immunoelectron microscopy using anti-62-kDa N-acetylmuramyl-L
      alanine amidase or anti-51-kDa endo-beta-N-acetylglucosaminidase immunoglobulin
      G. Protein A-gold conjugates reacting with antigen-antibody complex localized at
      sites of defects of the cell wall at the nascent cross wall. Anti-62-kDa N
      acetylmuramyl-L-alanine amidase or anti-51-kDa endo-beta-N-acetylglucosaminidase
      immunoglobulin G inhibited the decreased turbidity caused by PCG-induced lysis
      and the formation of defects in the wall. The autolysis-defective mutant, S.
      aureus RUSAL2 (atl::Tn551), exposed to 4 MIC of PCG resisted autolysis and
      formation of the wall defect. These results suggest that activation or
      deregulation of the atl gene products at localized sites where formation of new
      cross wall was disturbed by PCG causes small defects in the cell wall in situ,
      eventually leading to general autolysis.

PMID- 9139915
TI  - Primary structure and functional analysis of the soluble transducer protein HtrXI
      in the archaeon Halobacterium salinarium.
AB  - Signal transduction in the archaeon Halobacterium salinarium is mediated by a
      family of 13 soluble and membrane-bound transducers. Here, we report the primary
      structure and functional analysis of one of the smallest halobacterial putative
      transducers, HtrXI. Hydropathy plot analysis of the primary structure predicts no
      membrane-spanning segments in HtrXI. The fractionation of the H. salinarium
      proteins confirmed that HtrXI is a soluble protein. Capillary assay with an HtrXI
      deletion mutant and a complemented strain revealed that this soluble transducer
      is involved in Asp and Glu taxis. In vivo analysis of the methylesterase activity
      of the htrXI-1 deletion mutant suggests that HtrXI plays an important role in the
      adaptation of the chemotactic responses to His, Asp, and Glu, which are
      attractants for halobacteria. Stimulation by Asp and Glu causes demethylation of
      HtrXI and of another putative transducer, HtrVII. But addition of His to
      halobacterial cells increases HtrXI methylation together with that of other
      putative transducers. In the absence of HtrXI, stimulation by either Glu or His
      does not decrease or increase the methylation of any putative transducers.
      Therefire, the HtrXI transducer appears to have a complex role in chemotaxis
      signal transduction.

PMID- 9139916
TI  - Isolation of mutants of Acinetobacter calcoaceticus deficient in wax ester
      synthesis and complementation of one mutation with a gene encoding a fatty acyl
      coenzyme A reductase.
AB  - Acinetobacter calcoaceticus BD413 accumulates wax esters and triacylglycerol
      under conditions of mineral nutrient limitation. Nitrosoguanidine-induced mutants
      of strain BD413 were isolated that failed to accumulate wax esters under nitrogen
      limited growth conditions. One of the mutants, Wow15 (without wax), accumulated
      wax when grown in the presence of cis-11-hexadecenal and hexadecanol but not
      hexadecane or hexadecanoic acid. This suggested that the mutation may have
      inactivated a gene encoding either an acyl-acyl carrier protein or acyl-coenzyme
      A (CoA) reductase. The Wow15 mutant was complemented with a cosmid genomic
      library prepared from wild-type A. calcoaceticus BD413. The complementary region
      was localized to a single gene (acr1) encoding a protein of 32,468 Da that is 44%
      identical over a region of 264 amino acids to a product of unknown function
      encoded by an open reading frame associated with mycolic acid synthesis in
      Mycobacterium tuberculosis H37Ra. Extracts of Escherichia coli cells expressing
      the acr1 gene catalyzed the reduction of acyl-CoA to the corresponding fatty
      aldehyde, indicating that the gene encodes a novel fatty acyl-CoA reductase.

PMID- 9139917
TI  - Characterization of pURB500 from the archaeon Methanococcus maripaludis and
      construction of a shuttle vector.
AB  - The complete sequence of the 8,285-bp plasmid pURB500 from Methanococcus
      maripaludis C5 was determined. Sequence analysis identified 18 open reading
      frames as well as two regions of potential iterons and complex secondary
      structures. The shuttle vector, pDLT44, for M. maripaludis JJ was constructed
      from the entire pURB500 plasmid and pMEB.2, an Escherichia coli vector containing
      a methanococcal puromycin-resistance marker (P. Gernhardt, O. Possot, M. Foglino,
      L. Sibold, and A. Klein, Mol. Gen. Genet. 221:273-279, 1990). By using
      polyethylene glycol transformation, M. maripaludis JJ was transformed at a
      frequency of 3.3 x 10(7) transformants per microg of pDLT44. The shuttle vector
      was stable in E. coli under ampicillin selection but was maintained at a lower
      copy number than pMEB.2. Based on the inability of various restriction fragments
      of pURB500 to support maintenance in M. maripaludis JJ, multiple regions of
      pURB500 were required. pDLT44 did not replicate in Methanococcus voltae.

PMID- 9139918
TI  - Characterization of a glucose-repressed pyruvate kinase (Pyk2p) in Saccharomyces
      cerevisiae that is catalytically insensitive to fructose-1,6-bisphosphate.
AB  - We have characterized the gene YOR347c of Saccharomyces cerevisiae and shown that
      it encodes a second functional pyruvate kinase isoenzyme, Pyk2p. Overexpression
      of the YOR347c/PYK2 gene on a multicopy vector restored growth on glucose of a
      yeast pyruvate kinase 1 (pyk1) mutant strain and could completely substitute for
      the PYK1-encoded enzymatic activity. PYK2 gene expression is subject to glucose
      repression. A pyk2 deletion mutant had no obvious growth phenotypes under various
      conditions, but the growth defects of a pyk1 pyk2 double-deletion strain were
      even more pronounced than those of a pyk1 single-mutation strain. Pyk2p is active
      without fructose-1,6-bisphosphate. However, overexpression of PYK2 during growth
      on ethanol did not cause any of the deleterious effects expected from a futile
      cycling between pyruvate and phosphoenolpyruvate. The results indicate that the
      PYK2-encoded pyruvate kinase may be used under conditions of very low glycolytic
      flux.

PMID- 9139919
TI  - An extreme clockwise switch bias mutation in fliG of Salmonella typhimurium and
      its suppression by slow-motile mutations in motA and motB.
AB  - Pseudorevertants (second-site suppressor mutants) were isolated from a set of
      parental mutants of Salmonella with defects in the flagellar switch genes fliG
      and fliM. Most of the suppressing mutations lay in flagellar region IIIb of the
      chromosome. One fliG mutant, SJW2811, gave rise to a large number of suppressor
      mutations in the motility genes motA and motB, which are in flagellar region II.
      SJW2811, which has a three-amino-acid deletion (delta Pro-Ala-Ala) at positions
      169 to 171 of FliG, had an extreme clockwise motor bias that produced inverse
      smooth swimming (i.e., swimming by means of clockwise rotation of a
      hydrodynamically induced right-handed helical bundle), and formed Mot(-)-like
      colonies on semisolid medium. Unlike previously reported inverse-swimming
      mutants, it did not show a chemotactic response to serine, and it remained
      inverse even in a delta che background; thus, its switch is locked in the
      clockwise state. The location of the mutation further underscores the conclusion
      from a previous study of spontaneous missense mutants (V. M. Irikura, M. Kihara,
      S. Yamaguchi, H. Sockett, and R. M. Macnab, J. Bacteriol. 175:802-810, 1993) that
      a relatively localized region in the central part of the FliG sequence is
      critically important for switching. All of the second-site mutations in motA and
      motB caused some impairment of motility, both in the pseudorevertants and in a
      wild-type fliG background. The mechanism of suppression of the fliG mutation by
      the mot mutations is complex, involving destabilization of the right-handed
      flagellar bundle as a result of reduced motor speed. The mutations in the MotA
      and MotB sequences were clustered to a considerable degree as follows: in
      transmembrane helices 3 and 4 of MotA and the sole transmembrane helix of MotB,
      at helix-membrane interfaces, in the cytoplasmic domains of MotA, and in the
      vicinity of the peptidoglycan binding region of the periplasmic domain of MotB.
      The potential importance of Lys28 and Asp33 of the MotB sequence for proton
      delivery to the site of torque generation is discussed.

PMID- 9139920
TI  - Quorum sensing in Vibrio anguillarum: characterization of the vanI/vanR locus and
      identification of the autoinducer N-(3-oxodecanoyl)-L-homoserine lactone.
AB  - Certain gram-negative pathogens are known to control virulence gene expression
      through cell-cell communication via small diffusible signal molecules termed
      autoinducers. This intercellular signal transduction mechanism termed quorum
      sensing depends on the interaction of an N-acylhomoserine lactone (AHL) auto
      inducer molecule with a receptor protein belonging to the LuxR family of positive
      transcriptional activators. Vibrio anguillarum is a gram-negative pathogen
      capable of causing a terminal hemorrhagic septicemia known as vibriosis in fish
      such as rainbow trout. In this study, we sought to determine whether V.
      anguillarum employs AHLs to regulate virulence gene expression. Spent V.
      anguillarum culture supernatants stimulated bioluminescence in a recombinant lux
      based Escherichia coli AHL biosensor strain, whereas they both stimulated and
      inhibited AHL-mediated violacein pigment production in Chromobacterium violaceum.
      This finding suggested that V. anguillarum may produce multiple AHL signal
      molecules. Using high-performance liquid chromatography and high-resolution
      tandem mass spectrometry, we identified the major V. anguillarum AHL as N-(3
      oxodecanoyl)-L-homoserine lactone (ODHL), a structure which was unequivocally
      confirmed by chemical synthesis. The gene (vanI) responsible for ODHL synthesis
      was cloned and sequenced and shown to belong to the LuxI family of putative AHL
      synthases. Further sequencing downstream of vanI revealed a second gene (vanR)
      related to the LuxR family of transcriptional activators. Although deletion of
      vanI abolished ODHL synthesis, no reduction of either metalloprotease production
      or virulence in a fish infection model was observed. However, the vanI mutant
      remained capable of weakly activating both bioluminescence and violacein in the
      E. coli and C. violaceum biosensors, respectively, indicating the existence of
      additional layers of AHL-mediated regulatory complexity.

PMID- 9139921
TI  - NodV and NodW, a second flavonoid recognition system regulating nod gene
      expression in Bradyrhizobium japonicum.
AB  - In Bradyrhizobium japonicum, members of two global regulatory families, a LysR
      type regulator, NodD1, and a two-component regulatory system, NodVW, positively
      regulate nod gene expression in response to plant-produced isoflavone signals. By
      analogy to other two-component systems, NodV and NodW are thought to activate
      transcription via a series of phosphorylation steps. These include the
      phosphorylation of NodV in response to the plant signal and the subsequent
      activation of NodW via the transfer of the phosphoryl group to an aspartate
      residue in the receiver domain of NodW. In this study, we demonstrated that NodW
      can be phosphorylated in vitro by both acetyl phosphate and its cognate kinase,
      NodV. In addition, in vivo experiments indicate that phosphorylation is induced
      by genistein, a known isoflavone nod gene inducer in B. japonicum. By using site
      directed mutagenesis, a NodWD70N mutant in which the aspartate residue at the
      proposed phosphorylation site was converted to an asparagine residue was
      generated. This mutant was not phosphorylated in either in vitro or in vivo
      assays. Comparisons of the biological activity of both the wild-type and mutant
      proteins indicate that phosphorylation of NodW is essential for the ability of
      NodW to activate nod gene expression.

PMID- 9139922
TI  - Identification and characterization of pbpA encoding Bacillus subtilis penicillin
      binding protein 2A.
AB  - Amino acid sequence analysis of tryptic peptides derived from purified penicillin
      binding protein PBP2a of Bacillus subtilis identified the coding gene (now termed
      pbpA) as yqgF, which had been sequenced as part of the B. subtilis genome
      project; pbpA encodes a 716-residue protein with sequence similarity to class B
      high-molecular-weight PBPs. Use of a pbpA-lacZ fusion showed that pbpA was
      expressed predominantly during vegetative growth, and the transcription start
      site was mapped using primer extension analysis. Insertional mutagenesis of pbpA
      resulted in no changes in the growth rate or morphology of vegetative cells, in
      the ability to produce heat-resistant spores, or in the ability to trigger spore
      germination when compared to the wild type. However, pbpA spores were unable to
      efficiently elongate into cylindrical cells and were delayed significantly in
      spore outgrowth. This provides evidence that PBP2a is involved in the synthesis
      of peptidoglycan associated with cell wall elongation in B. subtilis.

PMID- 9139924
TI  - In vivo construction of a hybrid pathway for metabolism of 4-nitrotoluene in
      Pseudomonas fluorescens.
AB  - Pseudomonas fluorescens 410PR grows on 4-nitrobenzoate but does not metabolize 4
      nitrotoluene. The TOL pWW0 delta pm plasmid converts 4-nitrotoluene into 4
      nitrobenzoate through its upper pathway, but it does not metabolize 4
      nitrobenzoate. P. fluorescens 410PR(pWW0 delta pm) transconjugants were isolated
      and found to be able to grow on 4-nitrotoluene. This phenotype was stable after
      growth for at least 300 generations without any selective pressure. P.
      fluorescens 410PR(pWW0 delta pm) converted 4-nitrotoluene into 4-nitrobenzoate
      via 4-nitrobenzylalcohol and 4-nitrobenzaldehyde. 4-Nitrobenzoate was metabolized
      via 4-hydroxylaminobenzoate and finally yielded NH4+ and 3,4-dihydroxybenzoate,
      which was mineralized.

PMID- 9139923
TI  - Characterization of the Bacillus subtilis thiC operon involved in thiamine
      biosynthesis.
AB  - The characterization of a three-gene operon (the thiC operon) at 331 min, which
      is involved in thiamine biosynthesis in Bacillus subtilis, is described. The
      first gene in the operon is homologous to transcription activators in the lysR
      family. The second and third genes (thiK and thiC) have been subcloned and
      overexpressed in Escherichia coli. ThiK (30 kDa) catalyzes the phosphorylation of
      4-methyl-5-(beta-hydroxyethyl)thiazole. ThiC (27 kDa) catalyzes the substitution
      of the pyrophosphate of 2-methyl-4-amino-5-hydroxymethylpyrimidine pyrophosphate
      by 4-methyl-5-(beta-hydroxyethyl)thiazole phosphate to yield thiamine phosphate.
      Transcription of the thiC operon is not regulated by thiamine or 2-methyl-4-amino
      5-hydroxymethylpyrimidine and is only slightly repressed by 4-methyl-5-(beta
      hydroxyethyl)thiazole.

PMID- 9139925
TI  - Cloning and characterization of cspL and cspP, two cold-inducible genes from
      Lactobacillus plantarum.
AB  - Two cold shock genes, cspL and cspP, have been cloned from two Lactobacillus
      plantarum strains. These genes, which are nonallelic, were present in all strains
      tested. The genes encode 66-amino-acid polypeptides related to each other and to
      the cold shock Csp family. Transcription of cspP rendered a single mRNA, while
      two cspL mRNAs were found with common 5' ends. The amounts of these transcripts
      increased moderately upon exposure of the cultures to cold.

PMID- 9139926
TI  - Identification of greA encoding a transcriptional elongation factor as a member
      of the carA-orf-carB-greA operon in Pseudomonas aeruginosa PAO1.
AB  - A homolog of the transcriptional elongation factor, GreA, was identified in
      Pseudomonas aeruginosa PAO1. The deduced amino acid sequence for GreA from this
      organism exhibits 65.2% identity to its counterpart in Escherichia coli K-12. The
      nucleotide sequence of greA from P. aeruginosa overlaps by four bases the 3'
      terminus of carB which encodes the large subunit of carbamoylphosphate
      synthetase. S1 nuclease experiments showed that level of the greA transcript is
      elevated approximately 10-fold under conditions of pyrimidine limitation,
      consistent with the conclusion that transcription is initiated from the
      previously identified pyrimidine-sensitive promoter upstream of the carA-orf-carB
      greA operon. Transcriptional fusion experiments showed the presence of an
      additional weak promoter within the carB sequence. A greA insertional mutant of
      Pseudomonas aerugionsa was constructed by gene replacement. The mutant derivative
      grew well in rich medium but did not grow in minimal medium supplemented by
      arginine and nucleosides. The greA phenotype was suppressed by secondary
      mutations at a relatively high rate, consistent with the notion of an important
      physiological role for GreA.

PMID- 9139927
TI  - Promoter mapping and transcriptional regulation of the iron-regulated Neisseria
      gonorrhoeae fbpA gene.
AB  - In this study, we have mapped the promoter region of the Neisseria gonorrhoeae
      ferric iron binding protein-encoding gene fbpA, determined the start point of
      transcription, and examined the accumulation of fbpA mRNA Primer extension
      analysis of the fbpA promoter region indicated a single transcriptional start
      site located 51 bp upstream of the ATG translational start site. Northern blot
      analysis with a 200-bp fbpA structural gene probe detected one transcript of 1.0
      kb in RNAs extracted from gonococcal cultures grown under iron-restricted
      conditions; the 1.0-kb transcript was observed to accumulate at a steady rate
      throughout the growth cycle. In comparison, in cultures grown under iron
      sufficient conditions, the intensity of the 1.0-kb transcript was reduced
      considerably. Isolation of total RNA from rifampin-treated cells indicated that
      the half-life of the 1.0-kb fbpA transcript in cells grown under iron-restricted
      conditions was 1.2 +/- 0.2 min, while that of the 1.0-kb fbpA transcript obtained
      from cultures grown under iron-sufficient conditions was 0.5 +/- 0.1 min. Taken
      together, our results indicate that the fbpA promoter is regulated by iron and
      that transcription and translation of FbpA are closely linked.

PMID- 9139928
TI  - Nucleotide sequence of the Mycobacterium leprae katG region.
AB  - Synthetic oligonucleotide primers based on the DNA sequence data of the
      Escherichia coli, Mycobacterium tuberculosis, and Mycobacterium intracellulare
      katG genes encoding the heme-containing enzyme catalase-peroxidase were used to
      amplify and analyze the Mycobacterium leprae katG region by PCR. A 1.6-kb DNA
      fragment, which hybridized to an M. tuberculosis katG probe, was obtained from an
      M. leprae DNA template. Southern hybridization analysis with a probe derived from
      the PCR-amplified fragment showed that the M. leprae chromosome contains only one
      copy of the putative katG sequence in a 3.4-kb EcoRI-BamHI DNA segment. Although
      the nucleotide sequence of the katG region of M. leprae was approximately 70%
      identical to that of the M. tuberculosis katG gene, no open reading frame
      encoding a catalase-peroxidase was detectable in the whole sequence. Moreover,
      two DNA deletions of approximately 100 and 110 bp were found in the M. leprae
      katG region, and they seemed to be present in all seven M. leprae isolates
      tested. These results strongly suggest that M. leprae lacks a functional katG
      gene and catalase-peroxidase activity.

PMID- 9139929
TI  - The ispB gene encoding octaprenyl diphosphate synthase is essential for growth of
      Escherichia coli.
AB  - The Escherichia coli ispB gene encoding octaprenyl diphosphate synthase is
      responsible for the synthesis of the side chain of isoprenoid quinones. We tried
      to construct an E. coli ispB-disrupted mutant but could not isolate the
      chromosomal ispB disrupted mutant unless the ispB gene or its homolog was
      supplied on a plasmid. The chromosomal ispB disruptants that harbored plasmids
      carrying the ispB homologs from Haemophilus influenzae and Synechocystis sp.
      strain PCC6803 produced mainly ubiquinone 7 and ubiquinone 9, respectively. Our
      results indicate that the function of the ispB gene is essential for normal
      growth and that this function can be substituted for by homologs of the ispB gene
      from other organisms that produce distinct forms of ubiquinone.

PMID- 9139930
TI  - Characterization of transcriptional regulation of the kdp operon of Salmonella
      typhimurium.
AB  - The transcriptional control of the kdpFABC (K+ transport) operon of Salmonella
      typhimurium was characterized with a lacZ fusion. The kdpFABC operon of this
      organism was induced by K+ limitation and high osmolality, and osmotic induction
      was antagonized by a high concentration of K+. In the trkA (sapG) kdp+ mutant
      background, high concentrations of K+ inhibited growth, along with repressing the
      kdp operon. This result, which has not been reported for Escherichia coli, is
      inconsistent with the model in which the signal for the induction of the kdp
      operon is turgor loss.

PMID- 9139931
TI  - A novel Arthrobacter beta-galactosidase with homology to eucaryotic beta
      galactosidases.
AB  - An Arthrobacter beta-galactosidase has homology with the lysosomal acid beta
      galactosidases from humans and mice and with a Xanthomonas manihotis enzyme.
      Phylogenetic analysis of the deduced amino acid sequence showed an unusual
      pattern, with this procaryotic enzyme clustering within the animal clade. The
      gene encodes a subunit of 52 kDa, and the enzyme appears to be active as a dimer.
      The enzyme hydrolyzed substrates with either a beta-1,4 or a beta-1,3 linkage.

PMID- 9139933
TI  - The integration host factor-DNA complex upstream of the early promoter of
      bacteriophage Mu is functionally symmetric.
AB  - Inversion of the ihf site in the promoter region of the early promoter of
      bacteriophage Mu did not influence the integration host factor (IHF)-mediated
      functions. IHF bound to this inverted site could counteract H-NS-mediated
      repression, directly activate transcription, and support lytic growth of
      bacteriophage Mu. This implies that the IHF heterodimer and its asymmetrical
      binding site form a functionally symmetrical complex.

PMID- 9139932
TI  - Cell wall anchoring of the Streptococcus pyogenes M6 protein in various lactic
      acid bacteria.
AB  - The M6 protein from Streptococcus pyogenes is the best-characterized member of a
      family of cell envelope-associated proteins. Based on the observation that the C
      terminal sorting signals of these proteins can drive cell wall anchoring of
      heterologous unanchored proteins, we have cloned and expressed the emm6
      structural gene for the M6 protein in various lactic acid bacteria (LAB). The
      emm6 gene was successfully expressed from lactococcal promoters in several
      Lactococcus lactis strains, an animal-colonizing Lactobacillus fermentum strain,
      Lactobacillus sake, and Streptococcus salivarius subsp. thermophilus. The M6
      protein was efficiently anchored to the cell wall in all strains tested. In
      lactobacilli, essentially all detectable M6 protein was cell wall associated.
      These results suggest the feasibility of using the C-terminal anchor moiety of M6
      for protein surface display in LAB.

PMID- 9139934
TI  - Heme compounds as iron sources for nonpathogenic Rhizobium bacteria.
AB  - Many animal-pathogenic bacteria can use heme compounds as iron sources. Like
      these microorganisms, rhizobium strains interact with host organisms where heme
      compounds are available. Results presented in this paper indicate that the use of
      hemoglobin as an iron source is not restricted to animal-pathogenic
      microorganisms. We also demonstrate that heme, hemoglobin, and leghemoglobin can
      act as iron sources under iron-depleted conditions for Rhizobium meliloti 242.
      Analysis of iron acquisition mutant strains indicates that siderophore-, heme-,
      hemoglobin-, and leghemoglobin-mediated iron transport systems expressed by R.
      meliloti 242 share at least one component.

PMID- 9139935
TI  - Sinorhizobium teranga bv. acaciae ORS1073 and Rhizobium sp. strain ORS1001, two
      distantly related Acacia-nodulating strains, produce similar Nod factors that are
      O carbamoylated, N methylated, and mainly sulfated.
AB  - We have determined the structures of Nod factors produced by strains
      representative of Sinorhizobium teranga bv. acaciae and the so-called cluster U
      from the Rhizobium loti branch, two genetically different symbionts of particular
      Acacia species. Compounds from both strains were found to be similar, i.e.,
      mainly sulfated, O carbamoylated, and N methylated, indicating a close
      relationship between host specificity and Nod factor structure, regardless of the
      taxonomy of the bacterial symbiont.

PMID- 9139936
TI  - Cardiac function in genetically engineered mice with altered adrenergic receptor
      signaling.
AB  - In disease states such as heart failure, catecholamines released from sympathetic
      nerve endings and the adrenal medulla play a central role in the adaptive and
      maladaptive physiological response to altered tissue perfusion. G protein-coupled
      receptors are importantly involved in myocardial growth and the regulation of
      contractility. The adrenergic receptors themselves are regulated by a set of
      specific kinases, termed the G protein-coupled receptor kinases. The study of
      complex systems in vivo has recently been advanced by the development of
      transgenic and gene-targeted "knockout" mouse models. Combining transgenic
      technology with sophisticated physiological measurements of cardiac function is
      an extremely powerful strategy for studying the regulation of myocardial
      contractility in normal animals and in models of disease states. The purpose of
      this review is to summarize current knowledge about the regulation of
      cardiovascular homeostasis involving signaling pathways through stimulation of
      adrenergic receptors.

PMID- 9139937
TI  - Macromolecular transport in the arterial intima: comparison of chronic and acute
      injuries.
AB  - Hypertension is a known risk factor for the development of atherosclerosis, which
      is characterized by the abnormal accumulation of low-density lipoprotein and
      other plasma-borne macromolecules. The goal of this study was to measure
      accumulation of a plasma-borne macromolecular marker, horseradish peroxidase
      (HRP; 44 kDa), in the aortic intima and media of chronically hypertensive rats.
      HRP transport in 2-yr-old spontaneously hypertensive rats (SHR) was compared with
      that in age-matched Wistar-Kyoto rats (WKY) under conditions in which blood
      pressures were not significantly different during the 15-min HRP circulation.
      Intimal accumulation and medial HRP concentration profiles were obtained from
      methacrylate-embedded sections after reaction with 3,3'-diaminobenzidine and
      H2O2. Data were analyzed using a mathematical model of macromolecular transport
      to quantify the permeabilities of endothelium and internal elastic lamina (IEL).
      Chronic hypertension increased endothelial permeability without a change in IEL
      permeability. An apparent convective flux of HRP into the intima of SHR raised
      intimal HRP to a concentration higher than that of HRP in the plasma. Our results
      suggest that the intimal accumulation of plasma-borne macromolecules from
      pressure-driven convection is normally minimized by an intact endothelium.
      Similar changes resulted from acute injury by lipopolysaccharide, suggesting
      endothelial injury could account for transport changes associated with
      hypertension. After either chronic or acute endothelial damage, transport of
      macromolecules into the intima increases, but the IEL continues to retard
      transport of macromolecules beyond the intima, resulting in increased intimal
      accumulation.

PMID- 9139938
TI  - Interaction between adenosine and flow-induced dilation in coronary microvascular
      network.
AB  - Previous studies have demonstrated that coronary microvessels are regulated by at
      least three possible means: metabolite-induced, shear-induced, and pressure
      induced (myogenic) mechanisms. Adenosine, a putative metabolic vasodilator,
      preferentially dilates downstream coronary microvessels, whereas the shear
      sensitive mechanism is detected predominantly in upstream larger microvessels.
      However, the interaction of these mechanisms and the significance of the
      heterogeneous vascular responsiveness in flow regulation have not been evaluated.
      These tasks cannot be performed experimentally because of several confounding
      factors that cannot be separated. Therefore, the present study employed a data
      based modeling approach to investigate the role of response heterogeneity in a
      coronary vascular network and to test the hypothesis that shear-sensitive
      mechanism or the myogenic mechanisms will enhance the vascular sensitivity to
      adenosine due to the heterogeneity of the vascular responsiveness. We obtained
      necessary data and developed empirical models for the responsiveness of single
      vessels to pressure, shear stress, and adenosine. With the single-vessel models,
      a network model was established based on the branching pattern of coronary
      microvessels, mass balance, and fluid mechanics laws. Model simulation predicted
      an enhanced vascular response to adenosine in the network. Such an enhancement is
      caused by the heterogeneous vascular response to adenosine and the predominant
      flow-induced dilation in the large arterioles. Preferential dilation of the
      downstream small arterioles to adenosine initiates an increase in flow and a
      decrease in pressure at upstream vessels. The increased flow activates the shear
      sensitive mechanism of the upstream large arterioles and further enhances the
      flow. This hemodynamic interaction contributes up to approximately 20% of the
      adenosine-induced flow increase and also reduces the adenosine-induced pressure
      drop. In contrast to the shear-sensitive mechanism, myogenic response contributes
      relatively little to the vascular response to adenosine. These results suggest
      that various vascular regulation mechanisms and the response heterogeneity of
      vessels of different sizes may act in an integrative fashion for the optimal
      control of microvascular perfusion.

PMID- 9139939
TI  - Nitric oxide-mediated neurogenic vasodilatation in isolated monkey lingual
      arteries.
AB  - In isolated monkey lingual arteries denuded of the endothelium and contracted
      with prostaglandin F2alpha, transmural electrical stimulation produced a
      contraction that was reduced by prazosin and reversed to a relaxation by
      additional treatment with alpha,beta-methylene ATP. The relaxation thus induced
      was abolished by tetrodotoxin and N(G)-nitro-L-arginine (L-NNA), a nitric oxide
      (NO) synthase inhibitor, and L- but not D-arginine restored the response in the L
      NNA-treated arteries. Under treatment with prazosin and alpha,beta-methylene ATP,
      the arterial strips responded to nicotine with a relaxation that was not
      influenced by atropine and timolol but was abolished by hexamethonium,
      oxyhemoglobin, and methylene blue. The nicotine-induced relaxation was abolished
      by L-NNA but not by N(G)-nitro-D-arginine and was reversed by L-arginine.
      Relaxations to exogenously applied NO (acidified NaNO2 solution) were not
      influenced by L-NNA but were abolished by oxyhemoglobin and methylene blue. The
      response was not affected in the strips made unresponsive to vasoactive
      intestinal polypeptide and calcitonin gene-related peptide by desensitization.
      Histochemical study demonstrated the presence of perivascular neurons containing
      neuronal NO synthase. It is concluded that monkey lingual arteries are innervated
      by vasoconstrictor nerves liberating norepinephrine and possibly ATP and also by
      nonadrenergic noncholinergic vasodilator nerves liberating NO as a
      neurotransmitter to activate soluble guanylate cyclase. Vasoactive intestinal
      polypeptide and calcitonin gene-related peptide do not appear to be involved in
      the neurogenic vasodilatation.

PMID- 9139940
TI  - Thyroid status and regulation of intracellular sodium in rabbit heart.
AB  - To examine the effect of thyroid status on the homeostatic control of
      intracellular Na+, we studied the effect of treatment of hypothyroid rabbits with
      3,5,3'-triiodothyronine (T3). Intracellular Na+ and pH (pHi) in papillary muscles
      and Na+-K+ pump current (Ip) in ventricular myocytes were measured with ion
      sensitive microelectrode and whole cell patch-clamp techniques. Na+ influx,
      estimated from the rate of increase in intracellular Na+ on sudden Na+-K+ pump
      blockade with dihydroouabain, and Na+ efflux, calculated from Ip, were similar.
      Treatment with T3 induced an increase in both Na+ influx and Ip. The treatment
      induced increase in Na+ influx was eliminated by 5-(N,N-dimethyl)amiloride (DMA)
      but not by tetrodotoxin. Treatment with T3 increased the rate of fall in pHi on
      exposure of the papillary muscles to DMA; when the buffer capacity was taken into
      account, the T3 treatment-induced increase in this rate corresponded well with
      the treatment-induced, DMA-inhibitable estimate of Na+ uptake. We conclude that
      thyroid hormone enhances both Na+-H+ exchange-mediated Na+ uptake and Na+-K+ pump
      mediated Na+ efflux.

PMID- 9139941
TI  - Contribution of ATP to oxidative stress-induced changes in action potential of
      isolated cardiac myocytes.
AB  - The role of ATP in oxidative stress-mediated changes in the cardiac action
      potential was investigated in isolated adult rat cardiac myocytes. Superfusion
      with H2O2 led to a decrease in the energy charge and depletion of nonprotein
      thiols and elicited hypercontracture of the myocytes. Treatment with 3
      aminobenzamide (3-AB), an inhibitor of protein ribosylation, increased the
      lifetime of H2O2-exposed myocytes and attenuated depletion of ATP and nonprotein
      thiols. H2O2-mediated DNA strand breaks were increased in the presence of 3-AB.
      On exposure to H2O2, myocytes patch clamped with 1 mM ATP in the pipette
      initially displayed prolonged action potential durations (APD), which were later
      markedly abbreviated and accompanied by the activation of ATP-sensitive K+
      currents (I(K,ATP)). The late decrease in APD was inhibited by glibenclamide
      (which inhibits I(K,ATP)), but the initial prolongation of the action potential
      was exacerbated. Treatment with 3-AB or recordings with 10 mM ATP in the patch
      pipette caused an initial delay in the expression of H2O2-induced changes, but
      later caused a more pronounced and sustained increase in APD. These interventions
      delayed the activation of I(K,ATP). Thus enhanced ribosylation (presumably due to
      activation of DNA repair) appears to be a significant source of ATP depletion
      under oxidative stress that, via activation of I(K,ATP), mediates oxidative
      modifications in the action potential.

PMID- 9139942
TI  - Decreased active vasodilator sensitivity in aged skin.
AB  - Older men and women respond to local and reflex-mediated heat stress with an
      attenuated increase in cutaneous vascular conductance (CVC). This study was
      performed to test the hypothesis that an augmented or sustained noradrenergic
      vasoconstriction (VC) may play a role in this age-related difference. Fifteen
      young (22 +/- 1 yr) and 15 older (66 +/- 1 yr) men exercised at 50% peak oxygen
      uptake in a 36 degrees C environment. Skin perfusion was monitored at two sites
      on the right forearm by laser-Doppler flowmetry: one site pretreated with
      bretylium tosylate (BT) to block the local release of norepinephrine and thus VC
      and an adjacent control site. Blockade of reflex VC was verified during whole
      body cooling using a water-perfused suit. CVC (perfusion divided by mean arterial
      pressure) at each site was reported as a percentage of the maximal CVC (%CVCmax)
      induced at the end of each experiment by prolonged local heating at 42 degrees C.
      Neither age nor BT affected the %CVCmax (75-86%) attained at high core
      temperatures. During the early rise phase of CVC, the %CVCmax-change in
      esophageal temperature (delta T(es)) curve was shifted to the right in the older
      men (effective delta T(es) associated with 50% CVC response for young, 0.22 +/-
      0.04 and 0.39 +/- 0.04 degrees C and for older, 0.73 +/- 0.04 and 0.85 +/- 0.04
      degrees C at control and BT sites, respectively). BT had no interactive effect on
      this age difference, suggesting a lack of involvement of the VC system in the
      attenuated CVC response of individuals over the age of 60 yr. Additionally,
      increases in skin vascular conductance were quantitatively compared by measuring
      increases in total forearm vascular conductance (FVC, restricted to the forearm
      skin under these conditions). After the initial approximately 0.2 degrees C
      increase in T(es), FVC was 40-50% lower in the older men (P < 0.01) for the
      remainder of the exercise. Decreased active vasodilator sensitivity to increasing
      core temperature, coupled with structural limitations to vasodilation, appears to
      limit the cutaneous vascular response to exertional heat stress in older
      subjects.

PMID- 9139943
TI  - Control of oxidative metabolism in volume-overloaded rat hearts: effect of
      propionyl-L-carnitine.
AB  - The objective of the present work was the assessment of metabolic events
      responsible for the improvement of hemodynamic function of volume-overloaded
      hearts from rats receiving propionyl-L-carnitine. A severe cardiac hypertrophy
      was induced in 2-mo-old rats by surgical opening of an aortocaval communication.
      Three months later, during in vitro perfusions with 1.2 mM palmitate, 11 mM
      glucose, and 10 IU/l insulin, the mechanical performance and overall energy
      turnover (myocardial O2 consumption) of hypertrophied rat hearts were
      significantly decreased under conditions of moderate and high workloads. These
      changes in cardiac energetics paralleled the decrease in total tissue carnitine
      content and alterations in exogenous palmitate oxidation. The oxidative
      utilization of glucose was also slightly depressed in volume-overloaded hearts
      while steady-state glycolysis rates increased, especially in hearts subjected to
      high mechanical loads. This slowing of metabolic pathways involved in acetyl-CoA
      generation resulted in decreased NADH availability and in an apparent substrate
      limitation of oxidative phosphorylation suggested by a failure of cytosolic
      unbound ADP to drive respiration. Long-term administration of propionyl-L
      carnitine normalized the degree of reduction of mitochondrial pyridine
      nucleotides and improved the kinetics of mitochondrial ATP production in volume
      overloaded hearts. The resulting acceleration of energy turnover was essentially
      related to improved oxidative utilization of glucose, but steady-state palmitate
      oxidation rates also increased in severely hypertrophied hearts. This concomitant
      acceleration of glucose and palmitate oxidation may be related to the particular
      experimental conditions (high exogenous palmitate concentrations, elevated
      workloads) used in this study. We assume that the increase in intracellular
      carnitine, together with a stimulation of acetyl-CoA demands related to high
      workloads, creates conditions that are compatible with the simultaneous relief of
      pyruvate dehydrogenase and carnitine palmitoyltransferase I. The resulting
      increase in the rate of steady-state ATP production improves, in turn, the
      mechanical activity of volume-overloaded hearts.

PMID- 9139944
TI  - Mechanisms of inactivation of L-type calcium channels in human atrial myocytes.
AB  - We used whole cell patch-clamp and microfluorimetric (indo 1) techniques to
      measure Ca2+ current through L-type Ca2+ channels (I(Ca)) and Ca2+ transients in
      human atrial myocytes. During 1-s depolarizing pulses, I(Ca) inactivation was
      biexponential. The rate of rapid inactivation was slowed by ryanodine and was
      correlated with the rate of rise of cytoplasmic free Ca2+ concentration (r =
      0.80, P < 0.01). Slower-phase I(Ca) inactivation was not affected by ryanodine
      but was accelerated by increasing the availability of Ca2+ to permeate the Ca2+
      channel. Thus Ca2+ released from the sarcoplasmic reticulum (SR) was responsible
      for most I(Ca) inactivation during the first 50 ms of a depolarization to 0 mV,
      and thereafter inactivation by Ca2+ permeating the channel predominated. Pure
      voltage-dependent inactivation had a much slower time course of development (tau
      > 2 s) and played a smaller role than Ca2+-dependent mechanisms over a duration
      comparable to that of an action potential. We conclude that human atrial myocytes
      show both voltage- and Ca2+-dependent I(Ca) inactivation, that Ca2+-dependent
      mechanisms predominate over the time course of an action potential, and that
      although both Ca2+ released from the SR and Ca2+ permeating Ca2+ channels play a
      role, SR-released Ca2+ is particularly important in early, rapid I(Ca)
      inactivation, whereas Ca2+ permeating Ca2+ channels is more important in the
      slower phase of Ca2+-dependent inactivation.

PMID- 9139945
TI  - PKC-lambda is the atypical protein kinase C isoform expressed by immature
      ventricle.
AB  - We recently identified a developmental decline in protein kinase C (PKC) isoform
      expression, at the level of the protein, in rat ventricular myocardium. To
      investigate mechanisms regulating PKC isoform expression in cardiac tissue, this
      study uses Northern blot analysis to compare the abundance of PKC isoform mRNAs
      in neonatal and adult rat ventricular myocardium. PKC-epsilon protein and mRNA
      were detected in both neonatal and adult rat ventricular myocardial preparations.
      In contrast, coordinate postnatal declines in the abundance of PKC-alpha and PKC
      delta proteins and transcripts were identified. An antiserum raised against the
      COOH-terminal sequence of PKC-zeta detected abundant immunoreactivity in
      neonatal, but not adult, ventricular myocytes. However, PKC-zeta transcripts were
      not detectable in the heart either by Northern blot analysis or a reverse
      transcriptase-polymerase chain reaction approach, indicating that neither the
      myocytes nor the contaminating cellular elements in the heart express PKC-zeta.
      Rather, PKC-lambda, another atypical PKC isoform that is structurally highly
      homologous to PKC-zeta, was detected at the protein and mRNA level in neonatal,
      but not adult, ventricular myocardium. Taken together, these results establish
      that developmental declines in calcium-sensitive, novel, and atypical PKC
      isoforms are paralleled by changes in the levels of the mRNAs encoding these
      proteins, suggesting transcriptional regulation of PKC during normal cardiac
      development. The results of this study further identify PKC-lambda as the
      atypical PKC isoform expressed by the immature ventricle.

PMID- 9139946
TI  - Autonomic modulation of ventricular rate in atrial fibrillation.
AB  - This study investigated the changes in R-R interval in 23 patients (11 men and 12
      women; mean age 61 yr) with persistent atrial fibrillation in response to several
      provocative maneuvers including active postural change, Valsalva maneuver,
      handgrip, and rhythm-controlled respiration. Averaged R-R intervals were
      shortened immediately after postural change (from 797 +/- 35 ms supine to 677 +/-
      27 ms standing; P < 0.01) and recovered to the 90% level within 100 s. During
      Valsalva strain and handgrip, mean R-R intervals were significantly shortened
      (from 737 +/- 37 ms sitting to 697 +/- 38 ms in Valsalva and from 773 +/- 68 ms
      sitting to 701 +/- 58 ms in handgrip; both P < 0.01). During rhythm-controlled
      respiration, only two cases (10.5%) showed power peaks in spectrograms of moving
      window-averaged R-R intervals at the frequency corresponding to respiration
      rhythm. The ventricular response to atrial fibrillation is influenced by an
      increase in sympathetic tone and a decrease in parasympathetic tone but is not
      necessarily influenced by the increase in parasympathetic dominance. These
      results suggest that even in atrial fibrillation patients, the autonomic nervous
      system modulates the ventricular rate via the atrioventricular node and atrial
      tissue.

PMID- 9139947
TI  - Area postrema-induced inhibition of the exercise pressor reflex.
AB  - The exercise pressor reflex is opposed by the arterial baroreflex, and
      circulating peptides may act in the area postrema to enhance this inhibition.
      Therefore, we tested the hypothesis that the area postrema exerts an inhibitory
      effect on this reflex. Consequently, in six alpha-chloralose-anesthetized cats,
      blood pressure and heart rate responses to 30 s of electrically stimulated
      hindlimb contraction were compared before and after thermal coagulation of the
      area postrema. In six other cats, the same contraction-induced cardiovascular
      responses were assessed before and after chemical lesion of the area postrema
      using kainic acid (214 +/- 9 nl, 2.5-5 mM). Thermal lesion of the area postrema
      augmented blood pressure and heart rate responses to contraction from 29 +/- 5 to
      47 +/- 7 mmHg (P < 0.05) and from 8 +/- 2 to 14 +/- 2 beats/min (P < 0.05),
      respectively. Chemical lesion of the area postrema enhanced contraction-evoked
      blood pressure (30 +/- 7 vs. 47 +/- 6 mmHg, P < 0.05) and heart rate (12 +/- 4
      vs. 17 +/- 4 beats/min, P < 0.05) responses. These data suggest that the area
      postrema attenuates the exercise pressor reflex, possibly through the actions of
      circulating peptides on baroreflex function.

PMID- 9139948
TI  - Alterations in ATP-sensitive potassium channel sensitivity to ATP in failing
      human hearts.
AB  - Little is known about the involvement of preexisting heart disease on
      characteristics of ATP-sensitive K+ channels [I[K(ATP)]] in human heart. We have
      characterized I[K(ATP)] in isolated cardiac myocytes from patients with
      congestive heart failure (HF) and compared these channel characteristics with
      those from donor hearts (healthy control) using the patch-clamp technique. During
      metabolic inhibition induced by treatment with cyanide (1 mM) and 2-deoxyglucose
      (10 mM), action potential shortening occurred in atrial myocytes isolated from
      both HF and donors, but this response was significantly greater and sooner in HF
      than in donors. The action potential duration at 90% repolarization was 24.7 +/-
      4.1% (n = 15) of control in HF, whereas it was 58.7 +/- 5.9% (n = 10, P < 0.001)
      of control in donors measured at 30-min metabolic inhibition. The shortening of
      the action potential was partially reversed by glibenclamide (0.5 microM) in both
      groups. Consistent with the action potential measurements, the whole cell
      membrane current response to metabolic inhibition, evaluated by the differential
      current measurement, was sooner and greater in HF than in donors. Single-channel
      atrial I[K(ATP)] from both HF and donors, recorded in the excised inside-out
      patch configuration, exhibited bursting opening, conductance, and gating
      behaviors that did not differ between the two groups. However, the concentration
      of ATP at half-maximal inhibition of the channel in HF was greater (131.0 microM)
      than in donors (26.1 microM). We conclude that I[K(ATP)] in cardiac myocytes from
      patients with HF has channel characteristics substantially similar to those in
      donors, but that the channel is less sensitive to ATP inhibition in HF than in
      donors.

PMID- 9139949
TI  - Effects of elevated plasma epinephrine on glucose utilization and blood flow in
      conscious rat brain.
AB  - Acute glucoprivation increases cerebral blood flow (CBF), which is often
      attributed to the associated rise in plasma epinephrine levels. This study
      examined directly the effects of comparable increases in plasma epinephrine
      levels achieved by continuous intravenous infusions of epinephrine in
      normoglycemic, unanesthetized rats on local and overall CBF and cerebral glucose
      utilization (1CMRglc). CBF was determined by the autoradiographic
      [14C]iodoantipyrine method in six unanesthetized rats in which epinephrine
      dissolved in 1% ascorbic acid-1 mM EDTA was infused at a rate of 1 microg/min and
      in five normal controls infused with the vehicle alone. 1CMRglc was determined by
      the autoradiographic [14C]deoxyglucose method in six conscious rats infused
      similarly with the epinephrine solution and in six normal controls treated with
      the vehicle alone. The epinephrine infusions raised arterial plasma epinephrine
      levels 10- to 20-fold and increased arterial blood pressure and plasma glucose
      levels. Local CBF, however, was significantly changed (P < 0.05, Student's t
      test) in only 2 of 25 structures examined, and the changes were decreases not
      increases. 1CMRglc was not changed significantly in any of 42 brain structures
      examined, and average blood flow and glucose utilization in the brain as a whole
      were unaffected. These results show that high circulating levels of epinephrine
      similar to those accompanying glucoprivation alter neither local nor overall CBF
      and glucose utilization and cannot explain the increases in CBF associated with
      glucoprivation.

PMID- 9139951
TI  - Dietary cholesterol affects Na+-K+ pump function in rabbit cardiac myocytes.
AB  - Alterations in membrane cholesterol induced in vitro can alter Na+-K+ pump
      function. Because dietary cholesterol can influence membrane cholesterol in vivo,
      we examined if dietary cholesterol is a determinant of Na+-K+ pump function.
      Rabbits were fed cholesterol-supplemented diets for 1-4 wk. Cardiac myocytes were
      then isolated, and Na+-K+ pump currents (Ip) were measured using the whole cell
      patch-clamp technique. When the Na+ concentration in the patch pipettes ([Na]pip)
      was 10 mM, a modest diet-induced increase in serum cholesterol was associated
      with stimulation of Ip; large increases in serum cholesterol were associated with
      inhibition. There was no effect of modest or large increases in serum cholesterol
      on Ip when [Na]pip was 80 mM. The [Na]pip-Ip relationship determined using seven
      different levels of [Na]pip from 0 to 80 mM indicated that a modest increase in
      serum cholesterol increased the apparent affinity of the pump for cytoplasmic
      Na+. In contrast, dietary cholesterol had no effect on the apparent affinity of
      the pump for extracellular K+. We conclude that cholesterol intake influences the
      sarcolemmal Na+-K+ pump. This may have clinical implications for cardiovascular
      function.

PMID- 9139950
TI  - Beta-blockade reduces effects of adenosine and carbachol by transregulation of
      inhibitory receptors and Gi proteins.
AB  - Chronic blockade of stimulatory beta-adrenergic receptors may decrease inhibitory
      receptors of the adrenergic signal transduction system. This transregulation
      process might reduce the negative inotropic response of the myocardium to
      inhibitory receptor stimulation. Rats were treated for 6 days with the beta
      blocker atenolol (2 mg/day). beta-Adrenergic receptors in cardiac plasma
      membranes increased from 49 +/- 6 to 75 +/- 9 fmol/mg protein (means +/- SE; P =
      0.053), whereas muscarinic M2 receptors decreased (155 +/- 15 vs. 105 +/- 10
      fmol/mg protein; P < or = 0.05). Moreover, inhibitory G alpha(i) proteins were
      reduced by 36%. The functional responses of isolated hearts to inhibitory
      agonists after prestimulation with isoproterenol (3 nmol/l) were significantly
      blunted. The Ki value for the negative inotropic response of the maximal rise in
      developed left ventricular pressure (dP/dt(max)) to adenosine (0.1-100
      micromol/l) increased from 5.9 +/- 1.7 to 24.0 +/- 2.5 micromol/l (P < or =
      0.001). A similar rightward shift of the dose-response curve was observed for the
      effects of adenosine on developed left ventricular pressure (LVP) and of
      carbachol (0.01-10 micromol/l) on LVP and dP/dt. Thus chronic beta-blockade leads
      to a coordinate transregulation of inhibitory receptors and Gi proteins, reducing
      the effects of inhibitory receptor activation of the heart. This mechanism may
      contribute to the beneficial effects of beta-blocker therapy in heart failure.

PMID- 9139952
TI  - Adaptation of cardiac myosin and creatine kinase to chronic hypoxia: role of
      anorexia and hypertension.
AB  - The effects of chronic hypobaric hypoxia (CHH, 28 days, simulated altitude 5,500
      m) on the cardiac expression of myosin heavy chain (MHC) and creatine kinase (CK)
      was studied in rat left (LV) and right (RV) ventricle. To separate the effects of
      hypoxia from its associated perturbations, anorexia and pulmonary hypertension
      (resulting in RV hypertrophy), CHH animals were compared with normoxic controls
      (C) and with rats restricted in food supply (pair fed, PF). In RV, the increased
      proportion of beta-MHC in CHH (20 +/- 3%) vs. C (7 +/- 2%, P < 0.01) and vs. PF
      (12 +/- 2%, P < 0.05) rats was mainly attributed to hypertension. In contrast,
      the higher beta-MHC of CHH (23 +/- 2%) vs. C (13 +/- 2%, P < 0.05) in LV was
      mainly ascribed to anorexia (PF = 21 +/- 3%, not significant). A major
      contribution of anorexia was also evidenced in the isozymic profile of CK;
      anorexia accounted for a 25% decrease in mito-CK specific activity in LV, whereas
      hypertension partly accounted for the threefold increase in BB-CK in RV. CHH
      specifically induced a twofold rise in LV BB-CK. This suggests that both the
      expression of slow myosin, improving the economy of contraction, and the changes
      in CK isozymic profile could provide a biochemical basis for the CHH resistance
      to ischemia.

PMID- 9139953
TI  - Ca2+ sequestration as a determinant of chaos and mixed-mode dynamics in agonist
      induced vasomotion.
AB  - We have investigated the contribution of smooth muscle Ca2+ stores to chaotic
      vasomotion in isolated rabbit ear resistance arteries. In preparations
      constricted by histamine, exposure to cyclopiazonic acid (CPA) and thapsigargin
      (TSG), which inhibit the Ca2+-adenosinetriphosphatase (ATPase) pump of the
      sarcoplasmic reticulum, first induced then abolished highly characteristic mixed
      mode oscillatory behavior. The fractal dimension of the vasomotion, which
      reflects the minimum number of contributing dynamic variables, remained between 2
      and 4 until the point at which oscillations disappeared completely. By contrast,
      ryanodine, which attenuates Ca2+-induced Ca2+ release, decreased the fractal
      dimension of the responses to <2 in a graded concentration-dependent fashion by
      selectively suppressing a slow subcomponent of the overall rhythmic activity. CPA
      associated oscillations were insensitive to ryanodine but could be abolished by
      verapamil and modulated in an inhibitory or stimulatory fashion by charybdotoxin,
      which blocks Ca2+-activated K+ channels, and by ouabain, which blocks the Na+-K+
      ATPase. We conclude that there is nonlinear cross talk between CPA/TSG-sensitive
      Ca2+ stores and a membrane oscillator that regulates Ca2+ influx and that the
      kinetics of Ca2+ uptake by the CPA/TSG-sensitive pool can be distinguished
      dynamically from the kinetics of Ca2+ release from its ryanodine-sensitive
      subcomponent.

PMID- 9139954
TI  - Effects of dextran on microvascular ischemia-reperfusion injury in striated
      muscle.
AB  - The objectives of this study were 1) to elucidate the effects of dextran (Dx) at
      a nonhemodiluting dose of 5 mg/kg on ischemia-reperfusion injury in striated
      muscle and 2) to investigate whether the effects are dependent on the molecular
      weight of Dx. We used the model of a 4-h pressure-induced ischemia in the hamster
      skinfold chamber. By means of intravital microscopy the following parameters were
      assessed: vessel diameter, red blood cell velocity, rolling and adherent
      leukocytes, macromolecular extravasation, and functional capillary density. The
      animals received a continuous infusion (total dose 5 mg/kg) of dextran of
      different molecular weights or equivalent volumes of saline. Seven groups were
      studied: NaCl (control, n = 6), Dx 1 (n = 6), Dx 40 (n = 7), Dx 60 (n = 6), Dx 70
      (n = 7), Dx 110 (n = 7), and Dx 150 (n = 7). Leukocyte rolling was reduced by all
      Dx fractions, the difference from the control reaching significance 0.5 h after
      reperfusion in the Dx 60, Dx 70, and Dx 110 group, whereas leukocyte adherence
      was attenuated by > 40,000-mol-wt Dx at 0.5 h after reperfusion. Concomitantly,
      functional capillary density tended to improve after treatment with > or = 40,000
      mol-wt Dx. However, all Dx fractions studied failed to reduce postischemic
      macromolecular extravasation. These results provide evidence that Dx at 5 mg/kg
      attenuates postischemic microvascular disturbances; this effect is molecular
      weight dependent.

PMID- 9139955
TI  - A possible role for L-selectin in the release of polymorphonuclear leukocytes
      from bone marrow.
AB  - Previous studies from our laboratory have shown that the expression of L-selectin
      on polymorphonuclear leukocytes (PMN) is higher in the bone marrow than in
      peripheral blood. The present study was designed to determine the location of
      this L-selectin loss as the PMN pass from the hematopoietic tissue into venous
      sinusoids of the bone marrow. Bone marrow and peripheral blood samples were
      collected at the beginning, during, and just after five normothermic
      cardiopulmonary bypass procedures in which there was active marrow release and
      compared with five hypothermic procedures in which marrow release was suppressed
      by lowering body temperature to 27 degrees C. L-selectin expression was measured
      on PMN in the hematopoietic tissue and venous sinusoids in the bone marrow using
      quantitative histology and immunocytochemistry. At baseline there was more L
      selectin on PMN in the bone marrow hematopoietic tissue than in the sinusoids
      (24.7 +/- 3.5 vs. 10.3 +/- 2.5%, P < 0.004). Bone marrow release during
      normothermic cardiopulmonary bypass procedure was associated with a rise in
      peripheral blood band cells (0.18 +/- 0.7 vs. 2.98 +/- 0.56 x 10(9)/l, P < 0.01)
      and a further reduction of L-selectin expression on PMN in the sinusoids (P <
      0.03). Hypothermia (27 degrees C) prevented both the rise in peripheral blood
      band cells and the reduction in L-selectin on PMN in the sinusoids. In vitro
      studies showed that lowering the temperature had a similar effect on shedding of
      L-selectin from PMN. We conclude that PMN shed L-selectin as they move from the
      hematopoietic compartment into the venous sinusoids of the bone marrow and
      postulate that this could control the release of PMN from the marrow.

PMID- 9139956
TI  - Cytokine-induced leukocyte rolling in mouse cremaster muscle arterioles in P
      selectin dependent.
AB  - Leukocyte rolling and adhesion are generally observed in venules but rarely
      observed in arterioles. With the use of intravital microscopy, we found that a 4
      h treatment with interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha
      (TNF-alpha) dose dependently induced leukocyte rolling and adhesion in arterioles
      of the mouse cremaster muscle. The rolling response lasted more than 24 h and was
      completely inhibited by treatment with the sulfated polysaccharide fucoidin.
      Moreover, we found that costimulation with IL-1beta and TNF-alpha for 4 h
      synergistically increased arteriolar leukocyte rolling, i.e., threshold doses of
      IL-1beta and TNF-alpha together caused a more than 10-fold increase of rolling in
      arterioles compared with the sum of the individual responses. This rolling
      interaction was abolished by treatment with a monoclonal antibody directed
      against P-selectin (RB40.34), but it apparently was unaffected by a monoclonal
      antibody against L-selectin (MEL-14). Taken together, our functional data show
      that IL-1beta and TNF-alpha separately induce and synergistically increase P
      selectin-dependent leukocyte rolling and firm adhesion in mouse cremaster
      arterioles.

PMID- 9139957
TI  - Endothelial vasodilator production by uterine and systemic arteries. II.
      Pregnancy effects on NO synthase expression.
AB  - Pregnancy is characterized by elevations in uterine but not omental artery nitric
      oxide synthase (NOS)-specific activity. We hypothesized that increases in NO
      production during pregnancy are associated with elevations in protein expression
      of the constitutive isoform, endothelial cell NOS (ecNOS), in uterine but not
      systemic arteries. Arterial NOS-specific activity and guanosine 3',5'-cyclic
      monophosphate (cGMP) production were tested in pregnant sheep in the presence or
      absence [+5 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic
      acid] of Ca2+. With the use of Western analysis, ecNOS and neuronal NOS (nNOS)
      constitutive isoform expressions were evaluated in intact and denuded [vascular
      smooth muscle (VSM)] uterine and systemic (omental and renal) arteries as well as
      in isolated endothelium-derived proteins from nonpregnant and pregnant sheep.
      Uterine and omental artery NOS activity and cGMP production were inhibited 75-85%
      by Ca2+ removal. ecNOS was localized only in uterine and systemic artery
      endothelium (not VSM) by immunohistochemistry and Western analysis; nNOS was not
      detected. Compared with nonpregnant ewes, pregnancy increased expression of ecNOS
      in uterine [2.1- to 4.2-fold (P < 0.0001)] and omental [1.3- to 2.2-fold (P =
      0.032)] but not renal (P = 0.1367) artery endothelium. Increases in uterine were
      greater than in omental artery endothelium. Levels of plasma and urinary cGMP
      were elevated (P < 0.01) proportionally (1.8- to 2.0-fold) in pregnant versus
      nonpregnant ewes. During pregnancy, expression of uterine artery endothelium
      derived (not VSM) ecNOS constitutive isoform is increased, whereas expression in
      systemic vessels shows little or no change.

PMID- 9139958
TI  - Development of inwardly rectifying K+ channel family in rat ventricular myocytes.
AB  - The ATP-sensitive K+ current (I(K,ATP)), the inward rectifier K+ current (I(K1)),
      and the acetylcholine-activated K+ current (I(K,ACh)) were recorded in fetal,
      neonatal, and adult rat ventricular myocytes using the patch-clamp technique. The
      density (pA/pF) of I(K1) increased from gestation day 10 through neonatal day 1
      and then decreased after neonatal day 30. The density of I(K,ATP) activated
      maximally by metabolic inhibition changed in parallel with the I(K1) density, and
      the density of I(K,ATP) channel distribution was 1.3 times higher than that of
      I(K1) throughout the development. We failed to observe developmental changes in
      the single-channel conductance and the mean open time of I(K1) and I(K,ATP)
      channels. However, the open probability of the I(K,ATP) channel was lower in
      fetuses, and the sensitivity to ATP was highest in 1-day neonates. I(K,ACh) were
      present in the ventricle at all stages of development but at a much lower density
      than in atrium. The relationship between the resting membrane potential and the
      development of the inwardly rectifying K-channel family is discussed.

PMID- 9139959
TI  - 1,25-Dihydroxyvitamin D3 regulation of cardiac myocyte proliferation and
      hypertrophy.
AB  - We previously demonstrated that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] inhibits
      myocyte maturation (T. D. O'Connell, D. A. Giacherio, A. K. Jarvis, and R. U.
      Simpson. Endocrinology 136: 482-488, 1995). To define further the role of
      1,25(OH)2D3 in regulating myocardial development, we examined the effects of
      1,25(OH)2D3 on proliferation and growth of primary cultures of ventricular
      myocytes isolated from neonatal rat hearts. When neonatal myocytes were grown in
      a serum-supplemented medium, cell number approximately doubled, and treating
      these myocytes with 1,25(OH)2D3 inhibited their proliferation by 56.56% after 4
      days. Flow cytometry revealed that 1,25(OH)2D3 reduced the percentage of cells in
      the S phase of the cell cycle by 31.39% after 4 days. We show for the first time
      that proliferating cell nuclear antigen protein levels were specifically reduced
      by 1,25(OH)2D3. Protooncogene c-myc protein levels were also reduced by this
      hormone. Interestingly, a phorbol ester had a similar effect on myocyte
      proliferation. Furthermore, 1,25(OH)2D3 increased myocyte protein levels and
      increased cell size, suggesting that it induces cardiac myocyte hypertrophy. Our
      findings indicate that 1,25(OH)2D3 and phorbol esters directly regulate myocyte
      proliferation and induce myocyte hypertrophy. Finally, the data demonstrate that
      the mechanism by which 1,25(OH)2D3 regulates myocyte proliferation involves
      blocking entry into the S phase of the cell cycle.

PMID- 9139960
TI  - Modulation of propagation from an ectopic focus by electrical load and by
      extracellular potassium.
AB  - We previously developed a technique (R. Kumar, R. Wilders, R. W. Joyner, H. J.
      Jongsma, E. E. Verheijck, D. A. Golod, A. C. G. van Ginneken, and W. N. Goolsby.
      Circulation 94: 833-841, 1996) for study of a mathematical model cell with
      spontaneous activity, viz. a "real-time" simulation of a rabbit sinoatrial node
      cell (SAN model cell; R. Wilders, H. J. Jongsma, and A. C. van Ginneken. Biophys.
      J. 60: 1202-1216, 1991) simultaneously being electrically coupled via our
      "coupling clamp" [H. Sugiura and R. W. Joyner. Am. J. Physiol. 263 (Heart Circ.
      Physiol. 32): H1591-H1604, 1992] circuit to a real, isolated ventricular myocyte.
      We now apply this technique to investigate effects of coupling conductance (Gc),
      cell size, and the modulation of membrane potential by elevated extracellular
      potassium concentration on the ability of an ectopic focus, represented by the
      SAN model cell, to successfully drive a ventricular cell. Values of Gc and the
      relative sizes of the two cells define three possible outcomes: 1) spontaneous
      pacing of the SAN model cell but not driving of the ventricular cell, 2)
      cessation of spontaneous pacing, or 3) pacing of the SAN model cell and driving
      of the ventricular cell. Below a critical size of the SAN model cell only the
      first two of these outcomes is possible. Above this critical size there is a
      range of Gc that allows successful operation of the system as an ectopic focus.
      Elevation of extracellular potassium concentration from 4 to 8 mM increases both
      the lower bound and upper bound of Gc for this range. Elevation of extracellular
      potassium concentration, as commonly observed in myocardial ischemia, may have
      effects on either inhibiting or releasing from inhibition an ectopic focus.

PMID- 9139961
TI  - K+ and Cl- contribute to resting membrane conductance of cultured porcine
      endocardial endothelial cells.
AB  - The conventional whole cell patch-clamp technique was used to measure the resting
      membrane conductance and membrane currents of single, nonstimulated, cultured
      endocardial endothelial cells of the porcine right ventricle in different ionic
      conditions. All cells displayed the barium-sensitive, inwardly rectifying
      potassium (K+) current (I(Ki)). In 65% of the cells, I(Ki) was the predominant
      membrane current. The mean zero-current potential (V0) was -61.0 +/- 12.5 mV (+/-
      SD, n = 45). In 35% of the cells, I(Ki) was superposed on an outwardly rectifying
      (OR) current. V0 of these cells was more depolarized (-33.5 +/- 22.0 mV, n = 26).
      High intracellular Cl- (122 instead of 52 mmol/l) activated or increased the OR
      current and shifted V0 in the direction of the equilibrium potential for Cl-. In
      cells displaying the OR current, V0 was dependent on extracellular Cl-,
      indicating the contribution of an OR Cl- current in setting V0. At low
      intracellular Cl- (6 instead of 52 mmol/l), the OR current was decreased and V0
      shifted in the direction of the equilibrium potential for K+. In cells not
      displaying the OR current, V0 was dependent on extracellular K+ but not on Cl-,
      indicating major permeability to K+ in these conditions. Block of the OR current
      by the Cl(-)-channel blockers anthracene-9-carboxylic acid (1 mmol/l), flufenamic
      acid (100-500 micromol/l), and Zn2+ (100-200 micromol/l) provided further
      evidence for the anionic nature of the OR current. After inhibition of I(Ki) and
      the OR Cl- current, a third current component was observed in 50% of the cells.
      The pharmacology and voltage dependence of this current suggested the presence of
      Ca2+-activated K+ channels in endocardial endothelial cells. We concluded that
      the resting membrane conductance of nonstimulated endocardial endothelial cells
      is mainly determined by the combined activity of inwardly rectifying K+, OR Cl-,
      and Ca2+-activated K+ channels.

PMID- 9139962
TI  - Sympathetic and vascular responses to head-down neck flexion in humans.
AB  - Animal studies have demonstrated increases in sympathetic nerve outflow with
      vestibular stimulation. The purpose of the present study was to determine whether
      vestibulosympathetic reflexes are engaged in humans. Muscle sympathetic nerve
      activity (MSNA), heart rate, arterial pressure, calf blood flow (CBF), and
      calculated calf vascular resistance (CVR; mean arterial pressure/CBF) were
      determined during 10 min of baseline (laying prone with chin supported) and 10
      min of head-down neck flexion (HDNF). MSNA responses were measured in nine
      subjects, and calf vascular responses were determined in seven of these subjects.
      Heart rate increased during the first minute of HDNF (71 +/- 2 to 76 +/- 3
      beats/min; P < 0.05) and remained slightly elevated (71 +/- 2 to 74 +/- 3
      beats/min; P < 0.05) for the duration of HDNF. Diastolic and mean arterial
      pressures also increased slightly with HDNF (80 +/- 3 to 82 +/- 3 and 96 +/- 3 to
      98 +/- 3 mmHg, respectively; P < 0.05). Systolic arterial pressure did not change
      significantly during HDNF. CBF decreased 14% (4.63 +/- 0.78 to 3.97 +/- 0.60 ml x
      min(-1) x 100 ml(-1); P < 0.05), and CVR increased 12% (24.0 +/- 4.3 to 27.4 +/-
      4.7 units; P < 0.05) during HDNF. These changes corresponded with significant
      increases in MSNA during HDNF. MSNA, expressed as burst frequency, increased from
      14 +/- 2 to 20 +/- 2 bursts/min (P < 0.05) and increased 63 +/- 23% (P < 0.05)
      when expressed as the percent change in total activity. All variables returned to
      baseline during recovery. Thoracic impedance measured in five subjects did not
      change during HDNF (19.6 +/- 1.2 to 19.7 +/- 1.5 omega), suggesting no major
      change in central blood volume. The results indicate that HDNF elicits increases
      in CVR that are mediated by the augmentation of MSNA. Arterial pressure responses
      and thoracic impedance data suggest that high and low pressure baroreflexes were
      not the mechanism for sympathetic activation. The immediate increase in MSNA with
      HDNF suggests a role for vestibulosympathetic reflexes.

PMID- 9139964
TI  - Effects of relaxin on rat atrial myocytes. I. Inhibition of I(to) via PKA
      dependent phosphorylation.
AB  - The peptide hormone relaxin has direct, positive inotropic and chronotropic
      effects on rat hearts in vivo and in vitro. Relaxin's effects on the
      electrophysiological properties of single quiescent atrial cells from normal rats
      were investigated with a whole cell patch clamp. Relaxin had a significant
      inhibitory effect on outward potassium currents. The outward potassium current
      consisted of a transient component (I(to)) and a sustained component (I(S)). The
      addition of 100 ng/ml of relaxin inhibited the peak I(to) in a voltage-dependent
      manner (74% inhibition at a membrane potential of -10 mV to 30% inhibition at +70
      mV). The time to reach peak I(to) and the apparent time constant of inactivation
      of I(to) were increased by relaxin. Dialysis with the protein kinase A inhibitor
      5-24 amide (2 microM) prevented relaxin's effects, suggesting an obligatory role
      for this kinase in the relaxin-dependent regulation of the potassium current.

PMID- 9139963
TI  - Role of activation of calcium-sensitive K+ channels in NO- and hypoxia-induced
      pial artery vasodilation.
AB  - It has been previously observed that nitric oxide (NO) contributes to hypoxic
      pial artery dilation and that both sodium nitroprusside (SNP), a releaser of NO,
      and hypoxia elicit dilation via activation of ATP-sensitive K+ channels in the
      newborn pig. Other studies, however, have shown that NO activates calcium
      sensitive K+ (K(Ca)) channels. The present study, therefore, was designed to
      investigate the role of K(Ca)-channel activation in NO and hypoxic dilation and
      to relate this mechanism to the previously observed role of NO in hypoxic
      dilation in newborn pigs equipped with closed cranial windows. SNP (10(-8) and
      10(-6) M) elicited pial artery dilation that was unchanged in the presence of the
      K(Ca)-channel antagonist iberiotoxin (10(-7) M; 10 +/- 1 and 20 +/- 1 vs. 9 +/- 1
      and 20 +/- 2% for 10(-8) and 10(-6) M SNP in the absence and presence of
      iberiotoxin, respectively). Responses to S-nitroso-N-acetylpenicillamine and 8
      bromoguanosine 3',5'-cyclic monophosphate were similarly unchanged by
      iberiotoxin. In contrast, iberiotoxin attenuated the dilation resulting from
      moderate and severe hypoxia (arterial PO2 approximately 35 and 25 mmHg,
      respectively; 27 +/- 1 vs. 21 +/- 2 and 34 +/- 1 vs. 16 +/- 2% for moderate and
      severe hypoxia in the absence and presence of iberiotoxin, respectively).
      Iberiotoxin blocked responses to the K(Ca)-channel agonist NS-1619, whereas
      responses to the ATP-sensitive K+ agonist cromakalim were unchanged (8 +/- 1 and
      15 +/- 1 vs. 1 +/- 1 and 1 +/- 1% for 10(-8) and 10(-6) M NS-1619 in the absence
      and presence of iberiotoxin, respectively). These data show that NO and guanosine
      3',5'-cyclic monophosphate do not elicit dilation via K(Ca)-channel activation.
      However, activation of K(Ca) channels does contribute to hypoxic pial dilation.
      Finally, these data suggest that substances other than NO are involved in the
      contribution of K(Ca)-channel activation to hypoxic pial artery dilation.

PMID- 9139965
TI  - Effects of relaxin on rat atrial myocytes. II. Increased calcium influx derived
      from action potential prolongation.
AB  - Relaxin produces positive inotropic and chronotropic effects in rat hearts. The
      effect of relaxin on the action potential duration (APD) of single quiescent rat
      atrial cells was investigated with a whole cell patch clamp. Relaxin induced a
      significant, dose-dependent prolongation of the APD. This effect was maximal at
      200 ng/ml (nominal concentration of 33.6 nM), which caused, on average, a 57%
      increase in the time taken to reach 90% repolarization. The effect of relaxin was
      blocked by the protein kinase A inhibitor 5-24 amide, indicating that its effect
      is mediated by an adenosine 3',5'-cyclic monophosphate-dependent mechanism. The
      increased APD induced by relaxin caused an enhanced entrance of calcium, with the
      charge carried through voltage-activated calcium channels increased by
      approximately 25%. This increase was not due to a direct modulation of calcium
      currents (20); rather, it was a consequence of the longer period of cellular
      depolarization. Our findings that relaxin increased the APD and therefore
      increased the calcium influx in atrial myocytes could explain the positive
      inotropic effects induced by relaxin in atrial preparations.

PMID- 9139966
TI  - Gender difference in myogenic tone of rat arterioles is due to estrogen-induced,
      enhanced release of NO.
AB  - The characteristics of arteriolar myogenic responses of female rats have not been
      investigated. Thus experiments were conducted on isolated gracilis muscle
      arterioles (approximately 55 microm diameter) of four groups of 12-wk-old rats:
      male rats, female rats, ovariectomized female rats with no estrogen replacement
      (OV), and ovariectomized female rats with estrogen replacement (OV + E2, 50
      microg/kg s.c. injection of 17beta-estradiol benzoate every 48 h). Diameter
      changes in response to increases in perfusion pressure from 20 to 140 mmHg and to
      various concentrations of substance P (SP, 10(-9)-5 x 10(-8) M) and sodium
      nitroprusside (SNP, 10(-8)-10(-6) M) were measured before and after
      administration of N(omega)-nitro-L-arginine (L-NNA, 10(-4) M), an inhibitor of NO
      synthase. Arteriolar diameters of male and OV female rats were significantly less
      at 60-140 mmHg pressure than those of normal female and OV + E2 female rats (at
      80 mmHg, 45.4 +/- 1.8 and 43.1 +/- 2.2 vs. 58.4 +/- 1.6 and 57.3 +/- 1.3%). L-NNA
      elicited a significantly greater downward shift of pressure-diameter curves in
      arterioles of normal female and OV + E2 female rats than in arterioles of male
      and OV female rats (28.6 +/- 4.6 and 30.6 +/- 4.7 vs. 13.2 +/- 0.9 and 10.4 +/-
      2.6%). Dilations of arterioles from normal female and OV +/- E2 female rats to SP
      were significantly greater (by 50-60%) than those from male and OV female rats
      (20.8 +/- 1.8 and 22.3 +/- 1.9 vs. 13.8 +/- 1.4 and 13.8 +/- 0.6% at 10(-8) M). L
      NNA did not affect dilations to SNP but significantly reduced the dilation of
      arterioles in all groups to SP, more so in arterioles of male and OV female rats
      than in arterioles of the other two groups. We conclude that pressure-induced
      myogenic constriction of arterioles of female rats is less pronounced than that
      of male rats; this is, most likely, due to the enhanced release and/or activity
      of NO related to the presence of estrogen.

PMID- 9139967
TI  - Cell cycle effects of nitric oxide on vascular smooth muscle cells.
AB  - We characterized the cell cycle block induced by nitric oxide (NO) on smooth
      muscle cells (SMC). We hypothesized that the inhibition of SMC proliferation by
      NO was due to a specific block in cell cycle progression. Treatment of cultured
      rat aortic SMC with the NO donors S-nitroso-N-acetylpenicillamine or S
      nitrosoglutathione (0.1 mM for 48 h) resulted in a 50% decrease (P < 0.05) in the
      fraction of cells in the S and G2 + M phases and a corresponding increase in the
      G1 fraction, suggesting that NO inhibits entry into S phase, causing accumulation
      of cells in G1 phase. Application of both NO donors to cycling SMC resulted in a
      short-term, concentration-dependent (0.06-0.3 mM) inhibition of ongoing DNA
      synthesis as measured by radiothymidine incorporation, demonstrating that NO
      causes an S-phase arrest. The S-phase arrest by NO was not mimicked by exogenous
      guanosine 3',5'-cyclic monophosphate (cGMP, 10 mM) and was associated with, but
      not due to, a 20% inhibition of RNA synthesis. The S-phase block was completely
      reversed within 2 h of removal of the NO donors, similar to inhibition by the
      ribonucleotide reductase inhibitor hydroxyurea. Prolonged treatment of SMC with
      either NO donor (0.1 mM) did not synchronize cells at the G1-S boundary as
      expected after a prolonged S-phase arrest, but instead induced a quiescent G0
      like state characterized by a 12- to 18-h lag before DNA synthesis returned to
      normal levels after NO removal. These findings demonstrate that NO inhibition of
      SMC proliferation is associated with two distinct and reversible cell cycle
      arrests, an immediate cGMP-independent S-phase block followed by a shift back in
      the cell cycle from the G1-S boundary to a quiescent G0-like state.

PMID- 9139969
TI  - Memory and complex dynamics in cardiac Purkinje fibers.
AB  - The contribution of cumulative changes in action potential duration (memory) to
      complex cellular electrophysiological behavior was investigated in canine cardiac
      Purkinje fibers. Complex behavior induced during constant pacing was caused by
      reciprocal interactions between the time to full repolarization (TFR), where TFR
      = response duration + latency, and the diastolic interval (DI). The relationship
      between TFR and the preceding DI during complex behavior differed from that
      obtained using a standard restitution protocol. In particular, higher-order
      periodicities and chaos were produced in fibers in which the restitution curve
      lacked the prerequisites for such behavior. To investigate whether shifts in the
      restitution curve might be expected during rapid pacing, the relationship between
      TFR of a test response (TFR(n + 1)) and the immediately preceding response
      (TFR(n)) was determined. For any fixed DI(n), reduction of TFR(n) from 240 to 130
      ms was accompanied by a corresponding reduction of TFR(n + 1), whereas as TFR(n)
      was reduced further to 120 ms, TFR(n + 1) increased. Because of the dependence of
      TFR(n + 1) on TFR(n) (memory) and on the preceding DI(n) (restitution), the slope
      of the low-dimensional relationship between TFR(n + 1) and DI(n) at a constant
      pacing cycle length depended on the slopes of the restitution and memory
      functions. These results suggest that rapid accumulation and dissipation of
      memory may contribute importantly to complex electrical behavior in cardiac
      tissue.

PMID- 9139968
TI  - Ovariectomy eliminates sex differences in rat tail artery response to adrenergic
      nerve stimulation.
AB  - The influence of gonadal hormones on vasoconstrictor responses to adrenergic
      nerve stimulation was investigated by comparing tail arteries from intact and
      gonadectomized male and female Fisher 344 rats. Arterial ring segments from
      females were significantly less responsive to transmural nerve stimulation (1-8
      Hz) than arteries from age-matched males. Significant male-female differences
      persisted after correcting the contractile responses for sex-related differences
      in arterial mass, optimal resting tension, and maximal contractile force.
      Arteries were taken from cycling, intact females in either proestrus, estrus,
      metestrus, or diestrus, but no significant differences were found among the four
      stages for vasoconstrictor responses to either adrenergic nerve stimulation or
      exogenous norepinephrine. These data suggest adrenergic function in the artery is
      not affected by hormonal variations during the estrous cycle. After bilateral
      ovariectomy, however, contractile responses of female arteries to adrenergic
      nerve stimulation were increased to levels similar to those observed in male
      arteries. Orchidectomy of males, in contrast, had no effect on neural-evoked
      contraction. Low concentrations of norepinephrine also produced greater
      contractile responses in male compared with female arteries; however, this sex
      related difference was eliminated by orchidectomy but not ovariectomy. Taken
      together, the results indicate that circulating gonadal hormones contribute to
      gender differences observed in rat tail artery. Vasoconstrictor responses to
      exogenous norepinephrine appear to be enhanced by testicular hormones. In
      contrast, vasoconstriction induced by adrenergic nerve stimulation appears to be
      influenced by chronic exposure to circulating ovarian hormones, resulting in a
      smaller vascular response in female arteries.

PMID- 9139970
TI  - Flow-independent heterogeneity of brain capillary plasma perfusion after blood
      exchange with a Newtonian fluid.
AB  - Previous studies from our group have indicated a heterogeneity of plasma transit
      times in brain capillaries. The heterogeneity was decreased with increasing
      cerebral blood flow during hypercapnia. In the present study, the hypothesis was
      tested that these apparent changes in microvascular plasma perfusion
      heterogeneity depend on the existence of red blood cells (RBC). To this end, the
      blood of anesthetized and paralyzed rats was replaced by a shear rate-independent
      oxygen-carrying substitute, ultrapurified polymerized bovine hemoglobin (UPBHB).
      Cerebral blood flow ([14C]iodoantipyrine technique) or microvascular perfusion
      pattern (intravenous bolus injection of Evans blue and decapitation 3-4 s later)
      was measured. After exchange transfusion with UPBHB, cerebral blood flow still
      varied with arterial PCO2, whereas in contrast to the unexchanged condition, the
      heterogeneity of the intracapillary Evans blue concentration remained unchanged.
      Compared with the unexchanged normocapnic condition, the heterogeneity of
      intracapillary dye concentration was decreased by one-quarter. It is concluded
      that RBC contribute to the microvascular perfusion heterogeneity in the brain.

PMID- 9139971
TI  - Computer model of electrophysiological instability in very small heterogeneous
      ventricular syncytia.
AB  - Computer simulations based on a model of transmembrane currents and intracellular
      Ca2+ flux of an isolated guinea pig myocyte [Nordin, C. Am. J. Physiol. 265
      (Heart Circ. Physiol. 34): H2117-H2136, 1993] have previously shown that very
      small heterogeneous ventricular myocardial syncytia can be constructed in which
      trains of sustained, nondriven action potentials are initiated and terminated
      with critically timed premature stimulations by a nonreentrant mechanism. A more
      detailed examination of the characteristics of such syncytia and the nature of
      the responses is explored. When cells with the normal configuration of equations
      were connected by high-resistance gap junctions to other cells in which their
      configuration was modified to reproduce a myocyte with mild Ca2+ overload and two
      regenerative levels of diastolic potential, critically timed stimulations shifted
      the electrical response of the syncytium between a stable phase, in which all
      myocytes were quiescent until stimulated and generated full action potentials
      from resting potentials between -90 and -65 mV, and an oscillatory phase, in
      which all cells generated sustained trains of nondriven action potentials from
      takeoff potentials between -70 and -30 mV. The following predominant responses
      were observed in such syncytia: 1) a range of 40-60 ms starting at the refractory
      period with an inverse relationship between prematurity of the stimulation and
      time to the first upstroke of nondriven activity, followed by a much shorter
      period with a direct relationship; 2) a delay shorter than a full compensatory
      pause following single premature stimulations that do not terminate spontaneous
      action potentials; and 3) entrainment of nondriven action potentials with short
      bursts of stimulations at rates just above the intrinsic rate of spontaneous
      activity and termination at faster rates. The propensity to develop nondriven
      action potentials was enhanced by Ca2+ loading. Other simulations demonstrated
      that activity can propagate in syncytia of >100 myocytes from small foci to
      generate full action potentials in larger regions of normal cells. Analysis of
      the model shows that these patterns arise primarily from crucial, dynamic
      relationships among membrane potential, intracellular Ca2+ cycling, and gap
      junction currents. The results suggest that highly localized interactions between
      normal and depolarized myocytes in uncoupled heterogeneous syncytia may reproduce
      many of the characteristic responses of ventricular tachycardia.

PMID- 9139972
TI  - Infarct size reduction with the nucleoside transport inhibitor R-75231 in swine.
AB  - Adenosine (Ado) has been reported to be cardioprotective in several models of
      myocardial ischemia. The nucleoside transport inhibitor R-75231 (R-75) has been
      reported to enhance local Ado concentrations and postischemic recovery of
      function, but little is known regarding its effects on myocardial infarct size.
      The purpose of the present study was to determine the effects of R-75 on infarct
      size and to measure myocardial regional Ado concentrations. Studies were
      conducted in pentobarbital-anesthetized swine undergoing 60 min of coronary
      artery occlusion and 2 h of reperfusion. Control pigs (n = 8) were compared with
      those receiving R-75 (0.1 mg/kg i.v.) 15 min before either occlusion (Pre R-75, n
      = 8) or reperfusion (Rep R-75, n = 8). Interstitial fluid (ISF) Ado, coronary
      venous Ado, and infarct size (% of the region at risk) were measured. In the Pre
      R-75 group, ISF Ado concentrations were significantly increased before and during
      ischemia, reaching a peak value of 71.8 +/- 8.6 microM (vs. 16.8 +/- 0.8 microM
      in control). ISF inosine and hypoxanthine concentrations were significantly
      reduced during ischemia in Pre R-75 animals. Infarct size was smaller in Pre R-75
      compared with control (21.6 +/- 1.9 vs. 38.4 +/- 2.6%, P < 0.05). The Rep R-75
      group had significantly elevated coronary venous Ado concentrations but no
      increases in ISF Ado or reduction in infarct size (33.5 +/- 3.5%). These data
      indicate that R-75 increases myocardial Ado and reduces infarct size when
      administered before coronary occlusion. The R-75-induced reduction in infarct
      size appears to be related to the augmentation of ISF Ado before ischemia rather
      than to increased plasma Ado during reperfusion.

PMID- 9139973
TI  - Impulse response analysis of baroreceptor sensitivity.
AB  - The impulse response function (IRF) can express the dynamic relationship between
      systolic arterial pressure (SAP) and pulse interval (PI) and, consequently,
      represents an alternative method to assess baroreceptor sensitivity (BRS) in
      humans. Five normotensive and 13 hypertensive subjects (age 68 +/- 5 yr, range 60
      74 yr) were studied at rest in the supine position during baseline conditions and
      after injections of phenylephrine and sodium nitroprusside. SAP and PI signals
      were derived from multiple 5-min noninvasive recordings of arterial blood
      pressure (Finapres) and electrocardiogram. Standard estimates of BRS were
      obtained by the slopes of transient changes in SAP and PI after the injection of
      phenylephrine and sodium nitroprusside (BRS(PE) and BRS(SNP)) and by spectral
      analysis (alpha-index). Impulse responses were obtained by the inverse Fourier
      transform of the transfer function between PI and SAP. The temporal pattern of
      the IRF was characterized by a main peak at t = 0, preceded by a "trough" at t = 
      1 s. A mathematical model of the baroreflex suggests that the peak value of IRF
      is linearly related to the BRS. The peak value and its smoothed version were
      shown to be significantly correlated to alpha, BRS(PE), and BRS(SNP) and
      significantly reduced in the hypertensive group during the three stages of the
      protocol. We suggest that IRF might be the ideal method to assess BRS because it
      does not require any subjective preselection of data segments or spectral bands.

PMID- 9139974
TI  - Modulation of SERCA2 expression by thyroid hormone and norepinephrine in
      cardiocytes: role of contractility.
AB  - Decreased expression of the cardiac slow-twitch sarcoplasmic reticulum Ca2+
      adenosinetriphosphatase (SERCA2), a major determinant of Ca2+ homeostasis,
      contributes to the abnormal intracellular Ca2+ handling in the failing heart. We
      investigated the contractility dependence of the effects of norepinephrine (NE)
      and thyroid hormone (T3) on SERCA2 expression in cultured neonatal heart cells
      under serum-free conditions. NE and T3 are associated with pathological and
      physiological forms of hypertrophy, respectively, whereas both hormones increase
      contractility. In contracting cultures, T3 increased SERCA2 protein and mRNA
      levels by 35 and 110%, respectively. The same stimulatory effects of T3 on SERCA2
      expression were found in contraction-arrested cells. In contracting cultures, NE
      induced a decrease of SERCA2 protein and mRNA levels by 40 and 60%, respectively.
      In contrast, SERCA2 protein and mRNA levels were not decreased by NE in
      contraction-arrested cells, indicating that contractility is a prerequisite for
      the negative influence of NE on SERCA2 expression. Electrical stimulation at a
      fixed frequency in the presence and absence of NE demonstrated that the NE
      induced increase in contraction frequency is unlikely to account for the
      decreased SERCA2 expression induced by NE. The results suggest that the effect of
      contractility on SERCA2 expression depends on the signal transduction pathways
      that are activated by NE and T3.

PMID- 9139975
TI  - Arteriolar responses to extracellular ATP in striated muscle.
AB  - Blood flow and its distribution must be appropriately regulated to ensure that
      perfusion is matched to local tissue demands. We investigated the role of ATP in
      triggering a conducted alteration in arteriolar diameter in the Saran-covered
      cheek pouch retractor muscle of anesthetized hamsters (n = 60). Vascular
      responses were observed using in vivo video microscopy upstream from the site of
      micropressure application of ATP (10(-8)-10(-4) M) either into the lumen or just
      outside the wall of first- and second-order arterioles. The role of nitric oxide
      (NO) in the vascular responses to ATP was determined by inhibiting NO synthase
      activity with N(omega)-nitro-L-arginine methyl ester (L-NAME) with and without
      coadministration of an excess of L-arginine. Intraluminal application of ATP led
      to a concentration-dependent vasodilation, which was conducted upstream along the
      arteriole. The dilatory response was blocked by systemic pretreatment with L-NAME
      and was maintained in the presence of an excess of L-arginine. In contrast, ATP
      introduced extraluminally resulted in a conducted vasoconstrictor response that
      was enhanced by pretreatment with L-NAME. The dilator response to intraluminal
      ATP, in the context of ATP release from erythrocytes under conditions associated
      with decreased supply relative to demand, supports a role for the erythrocyte in
      communicating local tissue needs to the vasculature, enabling the appropriate
      matching of oxygen supply to demand.

PMID- 9139976
TI  - Uncontrolled sarcomere shortening increases intracellular Ca2+ transient in rat
      cardiac trabeculae.
AB  - Isolated cardiac muscle preparations suffer from damaged-end compliance that
      allows for substantial shortening of central sarcomeres during contractions in
      which the overall length of muscle is kept constant. The impact of uncontrolled
      sarcomere shortening during a twitch on the intracellular calcium transient in
      myocardium is unknown. Accordingly, in the present study we developed an
      iterative laser-diffraction feedback system that allowed for the accurate control
      of central-segment sarcomere length and simultaneous measurement of
      iontophoretically injected fura 2 fluorescence in isolated cardiac trabeculae. We
      compared fura 2 fluorescence signals recorded during regular twitches with
      twitches in which central sarcomere length (SL) was held constant by feedback
      control ("SL clamp" twitches). We found that uncontrolled sarcomere shortening
      was associated with a significant (P = 0.005) increase in the peak of the calcium
      transient and that the amount of this increase was directly correlated to the
      extent of central-segment sarcomere shortening (r2 = 0.92; P < 0.01). The time
      course of the calcium transient, however, was unaffected by the mode of
      contraction (P = 0.64). These findings have important implications for the
      interpretation of studies of myocardial calcium handling in which uncontrolled
      sarcomere shortening takes place during the twitch.

PMID- 9139977
TI  - Electrophysiological-anatomic correlates of ATP-triggered vagal reflex in the
      dog. IV. Role of LV vagal afferents.
AB  - The negative chronotropic action and the time to peak effect (t(p)) of ATP and
      its related analogs [2-methylthio-ATP (2-MeSATP), alpha,beta-methylene-ATP
      (alpha,beta-mATP), and beta,gamma-methylene-ATP (beta,gamma-mATP)] as well as
      ADP, AMP, and adenosine were determined in anesthetized dogs. Intra-right atrium
      (RA) and intra-left main coronary artery (LM) ATP markedly suppressed sinus node
      automaticity. ATP induced a much greater response when administered into the LM
      than into the RA. The t(p) of ATP administered at the former site was much
      shorter than that at the latter site. Intra-LM adenosine had either no effect or
      a relatively very small effect, and its t(p) was significantly longer than that
      of intra-LM ATP. Bilateral cervical vagotomy either abolished or markedly
      attenuated the effect of intra-RA and intra-LM ATP; under these conditions, the
      actions of ATP and adenosine and their t(p) values became similar. The structure
      function cascade of intra-LM ATP and its analogs was alpha,beta-mATP > 2-MeSATP >
      ATP > or = beta,gamma-mATP > ADP >> AMP = 0. The P2X-purinoceptor antagonist
      pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid markedly attenuated the
      negative chronotropic action of all purine nucleotides. It was concluded that 1)
      ATP triggers a cardiocardiac vagal depressor reflex by stimulating vagal afferent
      nerve terminals in the LV myocardium and 2) this action is mediated by P2X
      purinoceptors.

PMID- 9139978
TI  - Cardiac swelling-induced chloride current depolarizes canine atrial myocytes.
AB  - The effect of the cardiac swelling-induced chloride current (I(Cl,swell)) on the
      transmembrane potential was examined. Osmotic swelling affected the resting
      potassium current through an apparent dilution of intracellular potassium.
      Inflating cells by applying positive pressure to the patch electrode prevented
      the effect on the resting potassium current. Inflation depolarized dog atrial
      myocytes when the recording electrodes contained either 17 or 42 mM Cl-. The
      depolarization coincided with activation of I(Cl,swell) and was antagonized by
      the chloride-channel blocker niflumic acid. Substituting extracellular chloride
      with the more permeant ion SCN- shifted the reversal potential for I(Cl,swell) to
      more negative values and antagonized inflation-induced depolarization. The
      depolarization was accentuated by replacing extracellular chloride with a less
      permeant ion, aspartate. We conclude that activation of I(Cl,swell) in atrial
      cells causes significant depolarization of the resting membrane. The outward
      rectification of I(Cl,swell) and the high cell membrane resistance during the
      action potential plateau suggest that I(Cl,swell) will also have significant
      effects on atrial action potential configuration.

PMID- 9139979
TI  - Electrode for recording direction of activation, conduction velocity, and
      monophasic action potential of myocardium.
AB  - Conduction velocity and recovery of excitability are central facets of reentry
      arrhythmias, and yet there are no satisfactory techniques for the simultaneous
      measurement of both from the same area of myocardium. We have developed an
      electrode arrangement that allows the simultaneous recording of conduction
      velocity, repolarization of the myocardium together with an index of dispersion,
      and direction of activation of the myocardium. Three silver/silver chloride
      electrodes were arranged in an equilateral triangle with a reference electrode at
      the center. From this arrangement three monophasic action potentials were
      recorded. From the time of arrival of the wavefront of activation at each
      electrode the direction of activation and conduction velocity were calculated in
      real time by a computer. There was a good correlation for the in vivo signals
      from the circular electrode and the new electrode both for conduction velocity (r
      = 0.99, P < 0.001) and for direction of activation (r = 0.99, P < 0.001). This
      new mathematical method and electrode design allows the simultaneous measurement
      of conduction velocity and direction and monophasic action potential, and this
      can give a beat-by-beat indication of wavelength and dispersion of action
      potential duration.

PMID- 9139980
TI  - Spatiotemporal aspects of sympathetic C-fiber afferent activity in pressor reflex
      during abdominal ischemia.
AB  - Activation of abdominal sympathetic visceral afferents during ischemia elicits
      excitatory cardiovascular reflexes. The present study examined the time course
      and discharge patterns of activation of ischemically sensitive sympathetic C
      fiber afferents, and then the relationship between summated afferent activity and
      the pressor reflex induced by prolonged abdominal ischemia was determined. Single
      unit activity of abdominal C-fiber afferents was recorded from the right thoracic
      sympathetic chain of anesthetized cats during 30 min of ischemia. The reflex
      pressor response to abdominal ischemia was induced by occlusion of celiac and
      superior mesenteric arteries. Of 68 C-fiber afferents studied, 36 (approximately
      53%) were activated during 30 min of ischemia, whereas the activity of the
      remaining 32 were not altered. Onset latencies of 36 C-fiber afferents activated
      by ischemia ranged from 1.0 to 17.4 min with an average of 6.1 +/- 0.8 min. The
      majority of activated afferents manifested a bursting pattern of discharge
      activity as ischemia was prolonged beyond 10 min. Summated response of activated
      afferents, but not individual afferent activity, was related closely to the
      reflex pressor response during 30 min of ischemia. These results suggest that
      both recruitment of sufficient numbers of C-fiber afferents and adequate
      discharge frequency of afferents constitute an encoding mechanism for the pressor
      reflex during abdominal ischemia.

PMID- 9139981
TI  - Temporal effects of cytokines on neonatal cardiac myocyte Ca2+ transients and
      adenylate cyclase activity.
AB  - This study investigates the hypothesis that inflammatory cytokines, interleukin
      (IL)-1alpha IL-1beta, and tumor necrosis factor (TNF), influence cardiac function
      by affecting calcium homeostasis and that this effect is mediated by the beta
      adrenergic-adenylate cyclase system. After 4 days in culture, neonatal rat
      ventricular myocytes were treated with cytokines (10 ng/ml) for short (2 h) or
      longer (18 h) times. Myocyte calcium, contractility, and adenylate cyclase were
      measured under each condition. Anticipated stepwise increases in adenylate
      cyclase and intracellular calcium were found in controls (non-cytokine-treated)
      with 10(-7) M isoproterenol, 10(-7) M isoproterenol + 0.1 mM guanosine
      triphosphate, and 10(-9) M forskolin. Cells in the presence of cytokine for 2 h
      show increased basal calcium levels but no changes in adenylate cyclase
      activities, and isoproterenol fails to elevate adenylate cyclase levels or affect
      contractile shortening. After long-term treatment with IL-1beta or TNF, but not
      IL-1alpha, the significantly elevated levels of basal systolic calcium remain,
      and isoproterenol increases adenylate cyclase activity, unlike after short
      exposure. Forskolin maximally activates adenylate cyclase following both short-
      and long-term incubation, but the stepwise increase in activity is blunted
      following prolonged exposure. Thus short-term cytokine treatment blocks the
      adrenergic receptor-mediated increases in adenosine 3',5'-cyclic monophosphate,
      dissociating adenylate cyclase activation from cytokine-mediated increases in
      cell calcium, whereas longer treatment apparently produces direct affects on
      adenylate cyclase. Time-dependent differences in contractile response were found
      with IL-1alpha at 2 h and TNF at 18 h, implying that myofibrillar responsiveness
      to increased cytoplasmic calcium is dependent on both cytokine species and
      exposure time.

PMID- 9139983
TI  - Cardiac memory: a mechanical and electrical phenomenon.
AB  - Alterations in repolarization following prolonged periods of ventricular pacing,
      termed "cardiac memory," have been well documented. Postpacing changes in cardiac
      function have also been noted in hypertrophic cardiomyopathy. This study was
      designed to evaluate the effects of ventricular pacing on postpacing diastolic
      function and its relationship to repolarization changes. Eight subjects (mean
      age, 76 yr) with permanent pacemakers were enrolled in this study. Each subject
      was evaluated at a fixed pacing rate with recording of electrocardiographic and
      echocardiographic data. Seven sets of measurements were performed in the same
      sequential pattern: 1) after 1 wk of atrial pacing, 2) within 10 min after
      initiation of atrioventricular sequential pacing (ventricular pacing), 3) within
      10 min after termination of 1 h of ventricular pacing, 4) after 1 wk of
      ventricular pacing, and 5) within 10 min, at 1 h, and at 24 h after termination
      of ventricular pacing. All subjects had repolarization changes characteristic of
      cardiac memory only after 1 wk of ventricular pacing. Changes in repolarization
      parameters were accompanied by changes in peak left ventricular filling rate
      (dD/dt/D; P = 0.02) and isovolumic relaxation time (IVRT; P = 0.03) that at 24 h
      approached baseline values. Correlations existed between changes in the Q-T
      interval and IVRT (r = 0.53, P = 0.007) and between changes in T wave amplitude
      and dD/dt/D (r = 0.48, P = 0.018) after long-term ventricular pacing. Thus
      changes in both repolarization and diastolic function persist after cessation of
      ventricular pacing and lend support to the concept of electrical and mechanical
      cardiac memory.

PMID- 9139984
TI  - Diminished neurogenic but not pharmacological erections in the 2- to 3-month
      experimentally diabetic F-344 rat.
AB  - The rapid spread of locally restricted neural and hormonal signals among the vast
      array of largely inexcitable corporal smooth muscle cells is an absolute
      prerequisite to normal erectile function. And yet the mechanism(s) responsible
      for this phenomenon is not well understood. As a first step toward a more
      integrative understanding of erectile physiology and/or dysfunction, an 8- to 12
      wk period of experimental diabetes was induced in 2-mo-old male Fischer 344 rats
      by either intraperitoneal streptozotocin (STZ) injection (35 mg/kg; n = 22) or
      subtotal pancreatectomy (n = 11). Fourteen age-matched control animals received
      injection of vehicle only while nine others served as sham-operated control
      animals. Eight STZ-diabetic animals received insulin replacement. Erectile
      function was assessed by evaluation of penile reflexes and monitoring of
      intracavernous pressure responses to both electrical stimulation of the cavernous
      nerve and intracorporal papaverine or nitroglycerin injection. Intracavernous
      pressure responses to neurostimulation were significantly attenuated in both STZ
      diabetic and subtotal pancreatectomy animals compared with age-matched control
      animals (P < 0.05). Penile reflexes were also significantly diminished (P <
      0.05). Regression analysis revealed that diabetes-related decreases in
      neurostimulated intracavernous pressure responses were strongly correlated with
      diminished synaptophysin immunoreactivity in the corpora (P < 0.001; r = 0.88).
      However, there were no detectable diabetes-related differences in pharmacological
      erections induced by intracavernous papaverine or nitroglycerin injection.
      Northern analysis revealed a marked diabetes-related increase in the amount of
      connexin 43 mRNA measured in frozen corporal tissue. Insulin replacement
      partially restored (attenuated the loss of) synaptophysin immunoreactivity and
      maintained neurostimulated intracavernous pressure responses to control levels
      while having no effect on penile reflexes. These observations may have important
      implications to the understanding of erectile physiology as well as the etiology
      of diabetes-related erectile dysfunction.

PMID- 9139982
TI  - Myogenic contribution to agonist-induced renal vasoconstriction during normoxia
      and hypoxia.
AB  - Acute hypoxia attenuates agonist-induced constrictor and pressor responses in
      conscious rats, and a recent report suggests that hypoxia may also diminish
      myogenic reactivity in isolated, perfused rat kidneys. Thus we hypothesized that
      the diminished responsiveness to pressor agents during hypoxia is caused by an
      impairment of myogenic reactivity. Male Sprague-Dawley rats were instrumented
      with a pulsed Doppler flow probe on the left renal artery, an aortic vascular
      occluder cuff immediately above the left renal artery to control renal perfusion
      pressure, and catheters were inserted to measure systemic arterial blood pressure
      and renal arterial pressure (RAP) and for administration of agents. Animals were
      studied under normoxic or acute hypoxic (fractional concentration of O2 in
      inspired gials = 0.12) conditions and were administered phenylephrine, arginine
      vasopressin, or angiotensin II. To determine the myogenic (pressure-dependent)
      component of agonist-induced vasoconstriction, renal vascular resistance was
      calculated during agonist infusion with RAP uncontrolled and with RAP controlled
      to preinfusion levels. Significant myogenic components of agonist-induced renal
      vasoconstriction were evident with all pressor agents used. However, hypoxia did
      not attenuate agonist-induced, pressure-dependent increases in renal vascular
      resistance. We conclude that the reduced vasoreactivity associated with acute
      hypoxia is not caused by diminished myogenic reactivity.

PMID- 9139985
TI  - Lysophosphatidylcholine accumulation in cardiomyocytes requires thrombin
      activation of Ca2+-independent PLA2.
AB  - Lysophosphatidylcholine (LPC) accumulates during ischemia or following thrombin
      stimulation of cardiac myocytes. We determined whether LPC accumulation reflects
      increased LPC production via phospholipase A2 (PLA2) activation, inhibition of
      LPC catabolism, or a combination of both. Thrombin-stimulated normoxic myocytes
      demonstrated a 1.5-fold increase in LPC content and a 2- to 2.5-fold increase in
      membrane-associated, Ca2+-independent PLA2 activity. Despite PLA2 activation,
      hypoxia alone did not increase LPC content. Thrombin-stimulated hypoxic myocytes
      demonstrated a 2.5-fold increase in LPC content with no further increase in PLA2
      activity. Inhibition of Ca2+-independent PLA2 prevented the thrombin-induced
      increase in both PLA2 activity and LPC content under normoxic and hypoxic
      conditions. Pharmacological blockade of the hypoxia-induced inhibition of LPC
      catabolism did not affect hypoxia or thrombin-induced PLA2 activation or
      normoxic, thrombin-induced LPC accumulation but greatly diminished the magnitude
      of LPC accumulation after thrombin stimulation of hypoxic myocytes. Thus
      accumulation of LPC during ischemia or after thrombin stimulation is absolutely
      dependent on PLA2 activation and further augmented by inhibition of LPC
      catabolism.

PMID- 9139986
TI  - Latency of muscle chemoreflex to vascular occlusion of active muscle during
      dynamic exercise.
AB  - When oxygen delivery to active muscle is too low for the ongoing rate of
      metabolism, metabolites accumulate and activate a muscle chemoreflex that raises
      arterial pressure. During static muscular contractions, the latency of the onset
      of increments in sympathetic activity attributed to the muscle chemoreflex is
      long (1-2 min). This long latency might be caused by slow accumulation of
      metabolites attributable to low rates of metabolism. Because shortening
      contractions at a given force per unit time have a much higher energy cost than
      do static contractions, the muscle chemoreflex should have a much shorter latency
      during dynamic exercise than during static contractions, and the latency should
      shorten further with rising exercise intensity. To test these ideas, the latency
      to the onset of the rise in arterial pressure induced by the muscle chemoreflex
      following vascular occlusion of active muscle was measured in four dogs
      exercising on a treadmill. During steady-state exercise of mild to moderate
      intensity, pressor responses to muscle ischemia were elicited by rapid, complete
      occlusion of the terminal aorta; this procedure mimics the blockage of muscle
      blood flow that occurs normally during static contractions. There was a
      statistically significant effect of exercise intensity on latency (P < 0.001).
      The latency was 23.5 +/- 4.5, 16.4 +/- 5.6, and 10.1 +/- 2.3 s (means +/- SE) at
      3.2 km/h 0% grade, 6.5 km/h 0% grade, and 6.5 km/h 10% grade, respectively. Also,
      the rate of rise of arterial pressure during chemoreflex activation increased
      progressively with rising exercise intensity from 0.8 +/- 0.2 mmHg/s during
      exercise at 3.2 km/h 0% grade to 2.0 +/- 0.5 mmHg/s during exercise at 6.5 km/h
      10% grade. Thus the latency of the muscle chemoreflex in response to vascular
      occlusion during mild dynamic exercise is shorter than has been reported during
      static contractions of moderate intensity.

PMID- 9139987
TI  - Facilitation of postischemic reperfusion with alpha-PBN: assessment using NMR and
      Doppler flow techniques.
AB  - We examined the effects of the free radical spin trap N-tert-butyl-alpha
      phenylnitrone (PBN) on focal cerebral ischemia/reperfusion injury in halothane
      anesthetized rats. Ninety minutes after middle cerebral artery occlusion by an
      intraluminal filament, the artery was reperfused. Intravenous injections of 25
      mg/kg PBN 5 min before and 30 min after insertion of the filament significantly
      attenuated the lesion volume measured 24 h after ischemia. During ischemia and
      during the first 30 min after reperfusion, cerebral blood volume and blood flow
      were measured by volume-sensitive and newly developed flow-sensitive magnetic
      resonance imaging (MRI) techniques and by laser-Doppler flowmetry. In all animals
      the area of decreased blood flow was larger than the area of decreased volume by
      a factor of 2.2. The area of the postreperfusion flow deficits matched the final
      lesion volumes at 24 h measured histologically much better than did the blood
      volume deficits in both saline and PBN-treated animals. Reperfusion led to a
      return of blood flow and volume to values close to the contralateral side in the
      PBN-treated animals, in contrast to the saline-treated control group. We conclude
      that in focal ischemia/reperfusion PBN provides protection of the vascular
      endothelium, leading to enhanced postischemic reperfusion. The implication of
      this is that the vascular endothelium may be a primary target for the damaging
      action of free radicals given the protection afforded by putative spin traps.

PMID- 9139988
TI  - Estrogen reduces proliferation and agonist-induced calcium increase in coronary
      artery smooth muscle cells.
AB  - Epidemiological evidence and estrogen replacement studies suggest that estrogen
      has a protective effect on the cardiovascular system against coronary artery
      disease. Vascular smooth muscle (VSM) cell replication has been shown to play a
      causative role in the pathogenesis of atherosclerosis. Therefore, in this study,
      we investigated the effect of chronic treatment of cultured guinea pig coronary
      artery VSM cells with physiological concentrations of 17beta-estradiol (E2) on
      thymidine incorporation, cell proliferation, and bradykinin-stimulated cytosolic
      calcium concentration ([Ca2+]i). Bradykinin at physiological concentrations
      causes contraction of endothelium-denuded guinea pig coronary artery rings in a
      concentration-dependent manner. VSM cells were first treated with low doses of E2
      (10 pg/ml) for 1-2 days followed by treatment for 4-6 days with 50 pg/ml of E2, a
      concentration similar to that found in pregnancy. Using these protocols, we
      consistently observed the presence of E2-receptor mRNA in VSM cells by a
      ribonuclease protection assay. Fetal calf serum-stimulated [3H]thymidine
      incorporation was significantly reduced (P < 0.05) in E2-treated cells compared
      with untreated control cells. Similarly, E2 treatment significantly inhibited
      fetal calf serum-stimulated VSM cell proliferation compared with untreated
      control cells (P < 0.05). We also tested the hypothesis that E2 treatment
      attenuates agonist-stimulated [Ca2+]i in VSM cells because acute E2 treatment has
      been shown to produce relaxation of precontracted isolated coronary artery
      preparations. E2 treatment of VSM cells resulted in a significant decrease in
      bradykinin-stimulated [Ca2+]i compared with untreated cells (P < 0.05). In
      conclusion, our data demonstrate that estrogen at physiological concentrations
      directly regulates coronary VSM cell function.

PMID- 9139989
TI  - Indicator-dilution dispersion models and cardiac output computing methods.
AB  - The general theory of indicator-dilution methods provides a basis for computing
      improved cardiac output estimates. Interpretation is via indicator-dispersion
      modeling with Brownian motion of drifting particles. Detected curves indicate the
      distribution of passage times from the injection site: the local density random
      walk (LDRW) function of a Wiener process. Fitting the LDRW to 70 dye curves by
      nonlinear regression for examples, I show how all possible undistorted curves
      can, in principle, be simulated. I show via semilogarithmic plots that
      conventional exponential decay constructs systematically underestimate cardiac
      output by up to 8%. To help reconcile the predictions of LDRW-fitted dilution
      curves and contemporary practice, I show how curve-shape asymmetry (skewness)
      dramatically affects the enclosed areas. Mean transit times may overestimate
      blood volumes by 15-100% in very skewed thermodilution curves if the dispersion
      effects are overlooked. Triangle constructions, which accounted for hundreds of
      experimental findings, also have theoretical explanations. Curve-fitting methods
      reduce the extrapolation biases inherent in many computers and in any respiration
      induced artifacts. Compatibility of cardiac output predictions from various
      dilution methods and modules becomes feasible.

PMID- 9139990
TI  - Hodgkin-Huxley and partially coupled inactivation models yield different voltage
      dependence of block.
AB  - K+ channel blockers have been shown to exhibit complex time- and voltage
      dependent effects on cardiac K+ currents. Whereas much attention has been focused
      on the state dependence of K+ channel block, how a particular channel model can
      alter the predicted time and voltage dependence of channel block remains
      unexplored. In this study, using two different model formalisms for the same
      cardiac transient outward current channel, we compare the effects of a
      theoretical open-state specific channel blocker on macroscopic currents. Model 1
      is a Hodgkin-Huxley-like model, in which inactivation is an intrinsically voltage
      dependent process and occurs independently of activation. Model 2 is a "partially
      coupled" model, in which inactivation is intrinsically voltage insensitive but
      requires channel activation before it can proceed. In the absence of drug
      (blocking agent), the two models reproduce the macroscopic current data. In the
      presence of blocking agent, the two models can differ substantially, with model 1
      displaying much less block than model 2. We also examine simple mathematically
      convenient modifications to the Hodgkin-Huxley formalism, which reproduce some,
      but not all, of the use-dependent properties of block. Thus model formalism is
      important for analysis and simulation of state-specific drug-channel
      interactions.

PMID- 9139991
TI  - A fiber matrix model for the filtration through fenestral pores in a compressible
      arterial intima.
AB  - We advance a new hypothesis to explain the changes in hydraulic conductivity of
      an intact artery wall with transmural pressure previously observed by Tedgui and
      Lever [Am. J. Physiol. 247 (Heart Circ. Physiol. 16): H784-H791, 1984] and
      Baldwin and Wilson [Am. J. Physiol. 264 (Heart Circ. Physiol. 33): H26-H32,
      1993]. This hypothesis suggests that compaction due to pressure loading of the
      proteoglycan matrix in the arterial intima near fenestral pores of the internal
      elastic lamina (IEL) leads to a narrowing of the pore entrance area and a large
      decrease in local intrinsic Darcy permeability of the matrix. To quantitatively
      assess the feasibility of this mechanism, a local two-dimensional model is
      proposed to study filtration flow in the vicinity of fenestral pores in a
      compressible intima. Using a heterogenous fiber matrix theory, we first predict
      the change in Darcy permeability with intimal thickness (Li). The model then
      calculates local velocity profiles and pressure distributions in the intima and
      media. The results show a marked nonlinear steepening of intimal pressure
      profiles near fenestral pores when the intima thins at higher luminal pressures.
      The predicted relative change in resistances of the IEL (with intima, R(I)) and
      of the media (Rm) shows a steep increase in R(I)/Rm when Li is <20% of its
      unstressed value. Numerical results also suggest that intimal compression has a
      limiting behavior in which the much stiffer collagen fibrils inhibit further
      compaction at high pressures after the proteoglycan matrix is maximally
      compressed. Predictions are also presented to show how different transmural
      pressures alter growth of an intimal horseradish peroxidase spot that derives
      from a localized (a single cell's boundary) endothelial leakage. Such a
      prediction is amenable to experimental verification.

PMID- 9139992
TI  - Phase dependencies of the human baroreceptor reflex.
AB  - We studied the influence of respiratory and cardiac phase on responses of the
      cardiac pacemaker to brief (0.35-s) increases of carotid baroreceptor afferent
      traffic provoked by neck suction in seven healthy young adult subjects. Cardiac
      responses to neck suction were measured indirectly from electrocardiographic
      changes of heart period. Our results show that it is possible to separate the
      influences of respiratory and cardiac phases at the onset of a neck suction
      impulse by a product of two factors: one depending only on the respiratory phase
      and one depending only on the cardiac phase. This result is consistent with the
      hypothesis that efferent vagal activity is a function of afferent baroreceptor
      activity, whereas respiratory neurons modulate that medullary throughput
      independent of the cardiac phase. Furthermore, we have shown that stimulus
      broadening and stimulus cropping influence the outcome of neck suction
      experiments in a way that makes it virtually impossible to obtain information on
      the phase dependency of the cardiac pacemaker's sensitivity to vagal stimulation
      without accurate knowledge of the functional shape of stimulus broadening.

PMID- 9139993
TI  - A novel model of conduit coronary constriction reveals local actions of
      endothelin-1 and prostaglandin F2alpha.
AB  - We evaluated the effects of endothelin-1 (ET-1) and prostaglandin F2alpha
      (PGF2alpha) selectively on conduit coronary artery diameter using a novel
      approach in which the local concentration of vasoactive agent was controlled and
      maintained in vivo. ET-1 and PGF2alpha were applied topically (100 microl every 3
      min) to the external surface of the left circumflex coronary artery (LCx) in
      anesthetized dogs or to the bathing medium of isolated canine LCx rings in
      parallel in vitro experiments. The dose-dependent constrictions obtained in vivo
      and in vitro were similar with each agent. Single, approximately maximally
      effective concentrations of PGF2alpha evoked an initial rapid contraction
      followed by a slow and sustained larger contraction in both preparations. In
      contrast, single concentrations of ET-1 elicited a rapid constriction that
      partially recovered (50-80%) in the ensuing 1.5-2 h despite continuous exposure
      to ET-1. After the ET-1 constriction reversed, PGF2alpha could still elicit a
      contraction, indicating a homologous endothelin receptor desensitization. Both
      agents maximally decreased conduit artery cross-sectional area in vivo by
      approximately 40% without significantly changing LCx resistance. Thus this in
      situ technique revealed effects of ET-1 and PGF2alpha on a localized segment of
      coronary artery that were not discernible with either intravenous or
      intracoronary administration.

PMID- 9139994
TI  - Integrin-mediated reduction in vascular smooth muscle [Ca2+]i induced by RGD
      containing peptide.
AB  - It has previously been shown that synthetic peptides containing the sequence
      arginine-glycine-aspartic acid (RGD) cause vasodilation by activation of
      alpha(v)beta3-integrin present on vascular smooth muscle (VSM) cells. The purpose
      of this study was to determine whether this dilatory effect is mediated by a
      reduction in VSM cytosolic Ca2+ concentration ([Ca2+]i). First-order arterioles
      from the rat cremaster were isolated, cannulated, and pressurized. [Ca2+]i was
      quantitated from the ratio of emitted fluorescence intensity during alternate
      excitation of fura 2-loaded vessels at 340 and 380 nm. Cyclo(-Arg-Gly-Asp-D-Phe
      Val) (cycloRGD; 0.21-210 microM) produced a concentration-dependent dilation of
      arterioles that had developed basal myogenic tone. Over the entire concentration
      range tested, [Ca2+]i decreased from 91 +/- 6 to 27 +/- 4 nM (69.7 +/- 5.0%
      reduction). In association with the decrease in [Ca2+]i, arteriolar lumen
      diameter increased from 89 +/- 8 to 184 +/- 8 pm (89.8 +/- 1.8% dilation). At
      intermediate concentrations, cycloRGD induced rhythmic spiking of Ca2+
      superimposed on the concentration-dependent lowering of basal [Ca2+]i. These data
      directly link integrin activation with alterations in Ca2+ regulation, the net
      effect of which is a reduction in [Ca2+]i. These data further suggest that
      integrins, through their role in mediating cellular attachment to the
      extracellular matrix and in cellular signaling involving Ca2+, could provide a
      logical link to mechanotransduction and myogenic phenomena.

PMID- 9139995
TI  - Regional blood flow in Dahl-Iwai salt-sensitive rats and the effects of dietary L
      arginine supplementation.
AB  - The purpose of the present study was to determine 1) whether different organs
      undergo similar increase in vascular resistance in Dahl-Iwai salt-sensitive (S)
      rats, and 2) the effects of chronic oral L-arginine supplementation on the
      regional hemodynamics in S rats. Male 6-wk-old S rats and salt-resistant (R) rats
      were maintained on an 8% NaCl chow for 4 wk. One group (S or R rats) was
      maintained on tap water and the other group (S/Arg or R/Arg rats) received tap
      water containing L-arginine at a concentration of 1.5%. Organ blood flow and
      cardiac output were measured with microspheres in the conscious condition. Mean
      blood pressure in S, S/Arg, R, and R/Arg rats was 159 +/- 5, 138 +/- 3, 111 +/-
      4, and 112 +/- 4 mmHg, respectively. Urinary excretion of protein and albumin in
      S/Arg rats was significantly suppressed compared with S rats. Concerning regional
      hemodynamics, the flow rate of the kidney was lower in S rats than in R rats, but
      there were no differences between S and R rats in the flow rates of the brain,
      heart, lung, liver, spleen, intestine, skeletal muscle, and skin. Thus the renal
      blood flow was solely reduced in S rats on a high-salt diet. The flow rate of the
      kidney in S/Arg rats was maintained at a higher level compared with that of S
      rats. L-Arginine treatment tended to produce a recovery in the urinary excretion
      of guanosine 3',5'-cyclic monophosphate in S rats, but had no effect in R rats.
      Thus the supplementation of L-arginine prevented the increase in blood pressure
      in S rats on a high-salt diet and normalized the abnormality of renal
      hemodynamics accompanying salt-induced hypertension.

PMID- 9139996
TI  - Central 5-HT1A modulation of cardiovascular responses to tibial nerve stimulation
      evoked muscle contraction.
AB  - The effects of administering 8-hydroxy-2-(di-n-propylamine) tetralin [8-OH-DPAT,
      a serotonin 1A (5-HT1A) receptor agonist] into the rostral ventrolateral medulla
      (RVLM) on cardiovascular responses during tibial nerve stimulation-evoked muscle
      contraction were investigated using anesthetized rats. Stimulation of the tibial
      nerve (3 times motor threshold, 0.1 ms, 40 Hz) for 30 s increased mean arterial
      pressure (MAP), heart rate (HR), and muscle tension by 25 +/- 3 mmHg, 24 +/- 4
      beats/min, and 299 +/- 35 g, respectively. Bilateral microdialysis of 8-OH-DPAT
      (10 mM) for 30 min attenuated the stimulation-evoked increases in MAP (8 +/- 2
      mmHg) and HR (11 +/- 5 beats/min), without a change in muscle tension (292 +/- 30
      g). However, administration of 1 mM 8-OH-DPAT had no effect on the cardiovascular
      responses. Thirty minutes of microdialysis of 8-OH-DPAT (10 mM) into the caudal
      ventrolateral medulla produced no effect on cardiovascular responses during
      muscle contraction. Prior administration of 10 mM 1-[2-methoxyphenyl]-4-[4-(2
      phthalimido)-butyl]piperazine (NAN-190), a 5-HT1A receptor antagonist, for 30 min
      into the RVLM blocked the attenuating effects of subsequent microdialysis of 8-OH
      DPAT (10 mM). Results suggest that activation of 5-HT1A receptors within the RVLM
      inhibit cardiovascular responses elicited during static muscle contraction.

PMID- 9139997
TI  - Opioids in the nucleus of the solitary tract are involved in feeding in the rat.
AB  - We evaluated the effect of selective opioid peptides and naltrexone on feeding
      when injected into the nucleus of the solitary tract (NTS). Doses of 0, 1, 2, 4,
      and 8 nmol of [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO, mu-agonist), dynorphin
      A-(1-17) (DynA-(1-17), kappa-agonist), and [D-Ser2]leucine enkephalin-thr, (delta
      agonist) were injected into the NTS in satiated male rats, and food intake was
      measured at 1, 2, and 4 h. Only DAMGO significantly increased feeding above
      control levels at doses of 2, 4, and 8 nmol. Doses of 10 and 50 microg naltrexone
      in the NTS significantly decreased 18-h deprivation-induced feeding. These data
      suggest that NTS opioid receptors (primarily mu) may be involved in the
      regulation of feeding.

PMID- 9139998
TI  - Nitric oxide and renal effects of volume expansion in conscious monkeys.
AB  - Experiments were performed to determine the effects of nitric oxide (NO) synthase
      inhibition on the renal responses to volume expansion in conscious cynomolgus
      monkeys. All animals were volume expanded with 3% dextran in normal saline under
      three conditions: 1) during a control state, 2) during constant infusion of the
      NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 30 microg x kg(
      1) x min(-1)), and 3) during simultaneous infusion of L-NAME and excess NO
      substrate L-arginine (0.6 mg x kg(-1) x min(-1)). The control volume expansion
      increased urine flow from 0.27 +/- 0.05 to 0.94 +/- 0.28 ml/min and sodium
      excretion from 21 +/- 9 to 95 +/- 26 microeq/min. During L-NAME infusion, these
      responses were attenuated in that urine flow only increased from 0.13 +/- 0.03 to
      0.28 +/- 0.09 ml/min and sodium excretion from 13 +/- 8 to 35 +/- 23 microeq/min.
      Addition of L-arginine to the L-NAME infusion abolished these renal excretory
      effects of L-NAME alone. With combined L-NAME/L-arginine, volume expansion
      increased urine flow from 0.37 +/- 0.23 to 1.09 +/- 0.23 ml/min and sodium
      excretion from 38 +/- 27 to 150 +/- 24 microeq/min, responses similar to control.
      L-Arginine also markedly attenuated the effect of L-NAME to increase mean
      arterial pressure and abolished the L-NAME decreases in creatinine and p
      aminohippurate clearances. However, an L-NAME-induced bradycardia could only be
      partially reversed. These results demonstrate that a functioning NO system may be
      important in mediating normal renal responses to volume expansion in this primate
      species.

PMID- 9139999
TI  - Manifestation of circadian rhythm under constant light depends on lighting
      conditions during lactation.
AB  - Adult rats transferred to continuous illumination (LL) show a disruption of
      circadian rhythms, although the mechanisms underlying this effect are not yet
      well known. In previous experiments, we found that when rats were born and raised
      under LL they showed an ultradian pattern during the first 10 days after weaning,
      but afterward they generated a circadian rhythm that was maintained until
      adulthood. It was not clear whether this evolution was attributable to the
      influence of the rhythm of the mother or to the effect of constant light. Here,
      we have studied the motor activity rhythm of young rats maintained under LL after
      weaning, taking into account the conditions to which they were exposed during
      lactation [LL or continuous darkness (DD)]. To check the possible effect of the
      rhythm of the dam, on the day of delivery some of the dams were blinded, others
      were subjected to a restricted feeding schedule of 3 h/day, and the others were
      used as controls. For each rat, the period of the circadian rhythm and the
      percentage of variance explained by this rhythm were calculated. Results show
      that all rats maintained under LL during lactation expressed a circadian rhythm
      in their motor activity. However, rats maintained under DD during lactation did
      not. This effect did not seem to be dependent on the type of dam. These results
      suggest that the rhythm of the dams does not affect the manifestation of the
      rhythm of the pups and that the expression of circadian rhythmicity under
      constant bright light depends on the lighting conditions under which the animals
      were maintained during lactation, which could affect the development of the
      circadian pacemaker or the retina.

PMID- 9140000
TI  - Proadrenomedullin NH2-terminal 20 peptide has direct vasodilator activity in the
      cat.
AB  - The mechanism by which proadrenomedullin NH2-terminal 20 peptide (PAMP) decreases
      vascular resistance was investigated in the hindlimb vascular bed in the cat.
      Injections of PAMP, a shortened form of the peptide PAMP-(12-20), and
      adrenomedullin (ADM) into the hindlimb perfusion circuit elicit dose-related
      decreases in perfusion pressure. The order of potency was ADM > PAMP > PAMP-(12
      20), and the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8
      37) had no effect on vasodilator responses to PAMP or ADM. Vasodilator responses
      to PAMP were increased in duration by the adenosine 3',5'-cyclic monophosphate
      (cAMP) phosphodiesterase inhibitor Rolipram, whereas inhibitors of nitric oxide
      synthase and guanosine 3',5'-cyclic monophosphate phosphodiesterase had no
      effect. Vasodilator responses to PAMP were not altered by treatment with alpha
      receptor or adrenergic nerve terminal blocking agents and were similar in
      innervated and denervated hindlimb preparations. Responses to PAMP were similar
      when vasoconstrictor tone was increased by stimulation of the sympathetic nerves
      or infusion of phenylephrine and were not altered by the passage of time. These
      data suggest that PAMP dilates the hindlimb vascular bed by a direct cAMP
      dependent mechanism and that inhibition of norepinephrine release plays little if
      any role in mediating responses to the peptide in the regional vascular bed of
      the cat.

PMID- 9140001
TI  - Intracerebroventricular losartan inhibits postprandial drinking in sheep.
AB  - We investigated the contribution of brain angiotensinergic mechanisms to
      postprandial drinking in sheep. Sheep in fluid balance were given 0.8 kg chaff
      for 30 min, and water intake was measured for the next hour.
      Intracerebroventricular infusion of the AT1 type angiotensin II (ANG II) receptor
      blocker losartan (1 mg/h) reduced postprandial drinking by approximately 70% (n =
      7, P < 0.01) but did not affect food intake. The same losartan dose given
      intravenously had little or no effect on prandial drinking. Feeding increased Na+
      concentrations in plasma and cerebrospinal fluid (CSF; n = 5, P < 0.05).
      Intracerebroventricular losartan (1 mg/h) inhibited the drinking responses to
      intracarotid infusion of ANG II (0.8 microg/min for 30 min, n = 4, P < 0.01) and
      to intracerebroventricular infusion of 0.5 M NaCl (1 ml/h for 1 h, n = 5, P <
      0.05) but had no effect on drinking responses to intravenous infusion of 4 M NaCl
      (1.3 ml/min for 30 min). These findings indicate that a brain ANG II-dependent
      mechanism is involved in postprandial drinking in sheep. They suggest also that
      the mechanism by which increasing CSF Na+ causes thirst involves brain ANG II and
      is different from the mechanism subserving the drinking response to changes in
      blood Na+.

PMID- 9140003
TI  - Ovine fetal cardiovascular, renal, and fluid balance responses to 3 days of high
      arginine vasopressin levels.
AB  - To determine the effects of sustained high levels of arginine vasopressin (AVP)
      on the fetus and whether these effects were the same as those found during acute
      infusion of AVP, chronically catheterized fetal sheep aged 121-136 days were
      infused for 3 days with either AVP (45 mU x kg(-1) x h(-1)) or saline. The
      bradycardia, acidemia, and failure of glomerulotubular balance that occurred with
      acute AVP infusion were reversed by day 3 of AVP (P < 0.005) and the acute rise
      in arterial pressure was attenuated (P < 0.005). By contrast, the rise in the
      glomerular filtration rate was sustained (P < 0.005) and urinary osmolality
      increased further to 426 +/- 30 mosmol/kg (P < 0.01). Although placental blood
      flow did not change acutely with AVP, it had fallen by day 3 (P < 0.01). In
      addition, with AVP but not saline extracellular volume fell from 588 +/- 28 to
      493 +/- 29 ml/kg (P < 0.002) and the plasma/interstitial volume ratio rose from
      0.18 +/- 0.01 to 0.21 +/- 0.01 (P = 0.001). These findings suggest that although
      release of AVP may be beneficial in acute stress in utero, sustained high levels
      may be detrimental to fetal health and sodium balance.

PMID- 9140002
TI  - Na+-independent transport of bipolar and cationic amino acids across the luminal
      membrane of the small intestine.
AB  - The role of sodium in transport of bipolar and cationic amino acids and their
      interactions were examined in vitro by measuring unidirectional influx across the
      brush-border membrane of intact rat jejunal and rabbit ileal epithelia. The
      chloride-dependent and beta-alanine inhibitable B(0,+) present in rabbit ileum
      was blocked by combining inhibition by beta-alanine with Na(+)- or Cl(-)-free
      conditions. Under these conditions, lysine influx across the brush-border
      membrane is Na+ independent. All Na+-independent influx of cationic and bipolar
      amino acids is by a system b(0,+) equivalent in the brush-border membrane of both
      species, where a system y+ is not present. System b(0,+) is shown to be a potent
      exchanger of intracellular leucine for extracellular lysine and of intracellular
      lysine for extracellular leucine. The model used to explain leucine stimulation
      of mucosa to serosa lysine transport can explain Na+ dependence of net lysine
      absorption. On the assumption that b(0,+) in situ, like the transporter induced
      by retroperitoneal brown adipose tissue in Xenopus laevi oocytes, acts as an
      obligatory exchanger, this model can also explain the effects of lysine on short
      circuit current and net transport of sodium and the effect on transport capacity
      by preincubation at Na+-free conditions.

PMID- 9140004
TI  - BNP: pathophysiological and potential therapeutic roles in acute congestive heart
      failure.
AB  - Controversy persists regarding the acute responsiveness of atrial (ANP) and brain
      (BNP) natriuretic peptides in pathophysiological conditions such as acute heart
      failure (AHF). This study was designed to test the hypothesis that AHF is
      characterized by selective activation of ANP, but not BNP. We also hypothesized
      that BNP replacement in AHF would reduce cardiac filling pressures, increase
      sodium excretion, and inhibit circulating renin. Two groups of anesthetized dogs
      underwent rapid left ventricular pacing to induce AHF. Group 1 (n = 7) served as
      control and group 2 (n = 7) received canine BNP (10 ng x kg(-1) x min(-1)).
      Cardiorenal parameters, circulating natriuretic peptides, 3',5'-cyclic guanosine
      monophosphate (cGMP), and plasma renin activity (PRA) were determined at baseline
      and during AHF in both groups. AHF was characterized by reductions in cardiac
      output (2.3 +/- 0.2 vs. 3.7 +/- 0.3 l/min, P < 0.05), pulmonary capillary wedge
      pressure (PCWP; 11.7 +/- 0.8 vs. 5.1 +/- 0.3 mmHg, P < 0.05), and selective
      activation of ANP (250 +/- 51 vs. 39 +/- 13 pg/ml, P < 0.05), with no increase in
      circulating BNP (49 +/- 15 vs. 60 +/- 16 pg/ml, P = not significant). Compared
      with control, exogenous supplemental BNP in AHF resulted in marked increases in
      circulating cGMP (65 +/- 6 vs. 18 +/- 5 pg/ml, P < 0.05), with reductions in PCWP
      (9.1 +/- 0.9 vs. 12.9 +/- 1.1 mmHg, P < 0.05) and increased urinary sodium
      excretion (120 +/- 36.8 vs. 24 +/- 6.3 microeq/min, P < 0.05) via reductions in
      distal tubular sodium reabsorption (94.3 +/- 1.8 vs. 98.0 +/- 0.4%, P < 0.05).
      Exogenous BNP prevented the increase in PRA that occurred in the control group.
      We conclude that AHF is characterized by a failure to increase circulating BNP
      underscoring differential physiological and pathophysiological roles for ANP and
      BNP in states of immediate cardiac overload. These studies also support a
      potential role for BNP in the therapeutics of AHF.

PMID- 9140005
TI  - Effect of exposure to hypoxia from birth on aldosterone in rabbits: role of
      unesterified fatty acids.
AB  - Hypoxia and fluid and electrolyte disturbances are serious risks to normal
      postnatal development. Because a decrease in inspired O2 (hypoxic hypoxia)
      inhibits aldosterone synthesis in the adult and aldosterone controls water and
      electrolyte balance, we studied adrenocortical function in rabbits exposed to
      normobaric normoxia or hypoxic hypoxia (fraction of inspired O2 0.09) from birth.
      At 21 days of age, rabbits were anesthetized, the adrenals were rapidly removed,
      and the adrenal capsules containing mostly zona glomerulosa cells were separated.
      Cells were dispersed with collagenase and studied in vitro. Hypoxia in vivo
      resulted in a 73% decrease in basal aldosterone release and a 86% decrease in
      adenosine 3',5'-cyclic monophosphate-stimulated aldosterone release in vitro. We
      hypothesized that increased unesterified fatty acids could be partly responsible
      for inhibition of aldosterone synthesis. Total serum unesterified fatty acids in
      hypoxic kits were significantly increased (298 +/- 14 micromol/l) compared with
      normoxic kits (184 +/- 31 micromol/l). When cells from hypoxic rabbits were
      washed with fatty acid-free albumin and studied under conditions devoid of fatty
      acids, aldosterone production was partially restored. Corticosterone production
      was not affected by washing. Washing had no effect on aldosterone synthesis by
      cells from normoxic rats. Finally, exposing washed zona glomerulosa cells to
      oleic acid (10-50 microM) inhibited aldosteronogenesis. We conclude that exposure
      to hypoxia from birth attenuates aldosterone production in part due to an
      increase in levels of unesterified fatty acid levels.

PMID- 9140006
TI  - Raising at thermoneutrality prevents obesity and hyperphagia in BAT-ablated
      transgenic mice.
AB  - Transgenic mice with ablation of brown adipocytes induced by brown adipocyte
      specific expression of diphtheria toxin A chain (DTA) driven by the uncoupling
      protein (UCP) promoter (UCP-DTA mice) become obese and hyperphagic (Lowell, B.
      B., V. S. Susulic, A. Hamann, J. A. Lawitts, J. Himms-Hagen, B. B. Boyer, L. P.
      Kozak, and J. S. Flier. Nature 366: 740-742, 1993). A deficit in energy
      expenditure for brown adipose tissue (BAT) thermogenesis in these mice is
      presumed to contribute to the development of obesity. The objective of the
      present study was to obviate any deficit in BAT thermogenesis by raising
      transgenic and control mice at thermoneutrality (35 degrees C), where both would
      have equally inactive BAT, to see whether this would prevent the obesity and the
      hyperphagia. Transgenic and control mice were raised from weaning (3 wk of age)
      to 8 wk of age at either 24 or 35 degrees C. Raising at 35 degrees C completely
      prevented development of obesity of UCP-DTA mice, as indicated by their normal
      carcass fat, normal weights of four major white adipose tissue depots, and normal
      size of white adipocytes. As seen before, transgenic mice raised at 24 degrees C
      had excess weight gain by 6 wk of age and by 8 wk had doubled carcass fat, an
      obesity characterized by increased white adipocyte size with no increase in
      number of adipocytes. The treatment also prevented hyperphagia of UCP-DTA mice,
      consistent with the hypothesized role of BAT thermogenesis in control of
      thermoregulatory feeding (Himms-Hagen, J. Proc. Soc. Exp. Biol. Med. 208: 159
      169, 1995). UCP-DTA mice thus differ from genetically obese mice (ob/ob, db/db)
      for which raising at thermoneutrality is known not to prevent either the obesity
      or the hyperphagia. Both the obesity and the hyperphagia of UCP-DTA mice appear
      to be due to their deficit in BAT thermogenesis.

PMID- 9140008
TI  - Acute hypoxia stimulates renin secretion and renin gene expression in vivo but
      not in vitro.
AB  - This study aimed at examining the influence of acute hypoxia on renin secretion
      and renin gene expression in the kidney. To this end, male Sprague-Dawley rats
      were exposed to severe hypoxic stress (8% O2) or to carbon monoxide (0.1% CO) for
      6 h, and plasma renin activity (PRA) and renal renin mRNA levels were determined.
      PRA values increased from 3 to 13 and 10 ng angiotensin I x h(-1) x ml(-1), and
      renin mRNA levels increased by 120 and 100% during hypoxia and CO, respectively.
      Lowering the PO2 from 150 to 20 or 7 mmHg in the gas atmosphere of primary
      cultures of renal juxtaglomerular cells had no influence on renin secretion and
      renin gene expression after 6 and 20 h. Our findings thus suggest that both
      arterial and venous hypoxia can be powerful stimulators of renin secretion and
      renin gene expression in vivo. Because renal denervation did not prevent
      stimulation of the renin system by hypoxia, the effect could be indirectly
      mediated via the baroreceptor-macula densa mechanism. Another potential mediator
      of the effect could be circulating catecholamines, since we found that plasma
      norepinephrine increased from 0.7 to 1.5 and 2.4 ng/ml and plasma epinephrine
      increased from 0.3 to 1.4 and 2.7 ng/ml during hypoxia and CO inhalation,
      respectively.

PMID- 9140007
TI  - Opioid growth factor is present in human and mouse gastrointestinal tract and
      inhibits DNA synthesis.
AB  - Native opioid peptides serve as growth factors in a number of normal and
      neoplastic cells and tissues. This study investigated the influence of opioids on
      circadian rhythm-dependent DNA synthesis in mouse esophagus during homeostatic
      renewal. In contrast to a labeling index (LI) of 24.0% at 0630 and 5.5% at 1600,
      disruption of opioid-receptor interaction by the potent opioid antagonist
      naltrexone hydrochloride (NTX; 10 mg/kg) in mice resulted in an elevation of 49%
      in DNA synthesis of esophageal epithelial cells at 1600, but had no effect at
      0630. Mice subjected to [Met5]enkephalin (1 mg/kg) had an LI that was decreased
      23% from control levels at 0630, but was unaffected at 1600. This decrease in DNA
      synthesis was blocked by concomitant administration of naloxone (10 mg/kg);
      naloxone alone had no influence on cell replicative processes. In tissue culture
      studies, NTX and OGF markedly increased and decreased, respectively, the LI from
      control values. Both opioid growth factor (OGF) and its receptor, zeta, were
      detected in all but the cornified layer of mouse esophageal epithelium and in the
      epithelial cells of the stomach and small and large intestines. In addition, both
      peptide and receptor were observed in the basal and suprabasal cells of human
      esophageal epithelium. These results indicate that an endogenous opioid peptide
      (OGF) and its receptor (zeta) reside in gastrointestinal epithelium and play a
      role in cellular renewal processes in a tonically inhibitory, direct, and
      circadian rhythm-dependent fashion.

PMID- 9140009
TI  - Cardiovascular effects of homologous bradykinin in rainbow trout.
AB  - Bradykinins have only recently been identified in fish, and a detailed analysis
      of their cardiovascular actions is lacking. The present study examines the
      cardiovascular effects of trout bradykinin ([Arg0,Trp5,Leu8]bradykinin; tBK) in
      conscious trout, Oncorhynchus mykiss. tBK (1-10 nmol/kg body wt bolus) produced
      triphasic pressor-depressor-pressor responses. In phase 1, cardiac output (CO),
      ventral aortic (P(VA)), dorsal aortic (P(DA)), and central venous pressure
      increased, whereas systemic (R(S)) and gill resistance (R(G)) were unchanged. In
      phase 2, R(G) increased, whereas R(S), CO, and heart rate decreased, reducing
      P(VA) and P(DA). Plasma prostaglandin E2 and the prostacyclin metabolite, 6
      ketoprostaglandin F1alpha, were significantly elevated during phase 2, whereas
      leukotrienes C4 and B4 and thromboxane B2 were unaffected. Phase 3 was produced
      by an increased CO and R(S) and the return of R(G) to control. Phase 1 pressor
      response was not blocked by inhibitors of cyclooxygenase, angiotensin-converting
      enzyme (ACE) or alpha-adrenoceptors (alpha-AD), whereas phase 2 depressor and
      plasma prostaglandin responses were prevented by cyclooxygenase inhibition. Phase
      3 was partially blocked by ACE and alpha-AD inhibitors and is a response to the
      preceding hypotension. In vitro, tBK only decreased vascular resistance in the
      perfused splanchnic or skeletal muscle-kidney preparations. These results show
      that although tBK has multiple effects on the trout cardiovascular system, none
      of the effects are due to direct tBK stimulation of vascular smooth muscle. Phase
      2 vasodilation has features consistent with release of vasodilator prostaglandins
      while the mechanism of phase 1 constriction is unknown.

PMID- 9140010
TI  - Ca2+ uptake by cardiac sarcoplasmic reticulum at low temperature in rat and
      ground squirrel.
AB  - The Ca2+ uptake by isolated cardiac sarcoplasmic reticulum (SR) was compared
      between Richardson's ground squirrels and rats at 37, 25, 15, and 5 degrees C.
      The rate of SR Ca2+ uptake in ground squirrels was significantly higher than in
      rats over the temperature range. This marked species difference was observed over
      a Ca2+ concentration range from 0.1 to 10 microM. The Arrhenius plot for Ca2+
      uptake was linear for ground squirrels between 37 and 5 degrees C but showed a
      depression from linearity for rats at 5 degrees C. This temperature sensitivity
      was also reflected in rat SR Ca2+-adenosinetriphosphatase activity. Analysis of
      [3H]ryanodine binding in SR suggests that more Ca2+ release channels are in an
      open state at low temperatures in rats than in ground squirrels. Together, these
      results suggest that species differences in the response of SR to low temperature
      may account for the rise in cytosolic free Ca2+ in cold-sensitive species and may
      be responsible, at least in part, for the inability of cold-sensitive hearts to
      function at low temperature.

PMID- 9140011
TI  - Modulation of ovine fetal adrenocorticotropin secretion by androstenedione and
      17beta-estradiol.
AB  - Parturition in sheep is initiated by increases in activity of the fetal
      hypothalamic-pituitary-adrenal axis. We have previously reported that cortisol
      negative feedback efficacy is decreased at the end of gestation. The present
      study was designed to test the hypothesis that increasing plasma estrogen and/or
      androgen concentrations in the fetus might increase plasma adrenocorticotropic
      hormone (ACTH) concentration, either by stimulating ACTH secretion or by altering
      the negative feedback effect of cortisol on ACTH. Fetal sheep were chronically
      catheterized and treated with no steroid (control), 17beta-estradiol, or
      androstenedione (each approximately 0.24 mg/day). After catheterization and
      implantation of steroid pellet, fetuses were subjected to two short (10 min)
      periods of sodium nitroprusside-induced hypotension with or without pretreatment
      with intravenous infusion of hydrocortisone sodium succinate (0.5 microg/min) to
      test fetal ACTH responsiveness to stress and cortisol negative feedback efficacy.
      Estradiol treatment significantly increased basal plasma ACTH and cortisol
      concentrations relative to control fetuses but did not interfere with the
      inhibition of ACTH secretion by cortisol. Fetal plasma ACTH responses to
      hypotension were significantly suppressed approximately 60% in both control and
      estradiol-treated groups. Androstenedione treatment significantly increased basal
      fetal plasma ACTH and decreased basal fetal plasma cortisol concentration.
      Androstenedione did not alter stimulated levels of fetal ACTH but did block the
      inhibition of stimulated ACTH by cortisol. We conclude that increased fetal
      cortisol and ACTH secretion at the end of gestation may be due to the combined
      effects of the gonadal steroids in that estradiol increases basal plasma ACTH
      secretion while androstenedione reduces cortisol negative feedback efficacy.

PMID- 9140012
TI  - Cardiovascular effects of microinjection of low doses of serotonin into the NTS
      of unanesthetized rats.
AB  - In the present study, we analyzed in conscious rats the effects of
      microinjections of serotonin (5-HT; pmol range) into the nucleus of the solitary
      tract (NTS) on basal mean arterial pressure (MAP) and heart rate (HR) and also on
      the reflex bradycardia induced by the activation of the baro- and chemoreflex
      evaluated 1 min after 5-HT microinjection into the NTS. The data show that
      unilateral microinjection of 5-HT in the picomolar range into the NTS of
      unanesthetized rats produced a dose-dependent decrease in MAP and HR, which was
      blocked by previous microinjection of ketanserin (250 pmol/50 nl) into the NTS.
      The changes in MAP and HR induced by 5-HT were of very short duration, with a
      return to baseline values a few seconds later. The cardiovascular responses to
      baro- or chemoreflex activation 1 min after 5-HT microinjection into the NTS did
      not differ from the control, indicating that low doses of 5-HT produced no effect
      on the cardiovascular reflexes tested at that time. The present data show that,
      as also observed in anesthetized rats, the microinjection of picomolar doses of 5
      HT into the NTS elicits the typical cardiovascular responses to baroreceptor
      activation. These effects, hypotension and bradycardia, seem to be mediated by 5
      HT2 receptors because both were blocked by a selective 5-HT2 receptor antagonist.
      However, since microinjection of 5-HT (1 pmol) into the NTS produced no changes
      in the cardiovascular responses to the baro- and chemoreflex activated 1 min
      later, the role of 5-HT2 receptors in the processing of the cardiovascular
      afferent messages in the NTS remains to be elucidated.

PMID- 9140013
TI  - An electroneutral anion exchange mechanism is present in brush-border membranes
      isolated from eel kidney.
AB  - The mechanism of bicarbonate translocation across the luminal membrane of the eel
      (Anguilla anguilla) kidney tubular cells was studied by monitoring the uptake of
      H14CO3- into isolated brush-border membrane vesicles. Results indicate that the
      presence of a transmembrane outwardly directed Cl- gradient was able to
      transiently accumulate H14CO3- into the vesicular space, whereas neither an
      inwardly directed sodium gradient nor a transmembrane electrical potential
      gradient (inside positive) was able to stimulate the H14CO3- influx. This anion
      dependent H14CO3- uptake was inhibited by 4,4'-diisothiocyanostilbene-2,2'
      disulfonic acid, suggesting that an anion exchanger was present in the brush
      border membrane vesicles.

PMID- 9140014
TI  - Influence of forced respiration on nonlinear dynamics in heart rate variability.
AB  - Although it is doubtful whether the normal sinus rhythm can be described as low
      dimensional chaos, there is evidence for inherent nonlinear dynamics and
      determinism in time series of consecutive R-R intervals. However, the
      physiological origin for these nonlinearities is unknown. The aim of this study
      was to test whether the known nonlinear input from spontaneous respiration is a
      source for the nonlinearities in heart rate variability. Twelve healthy subjects
      were examined in supine position with 3-h electrocardiogram recordings during
      both spontaneous and forced respiration in accordance with a metronome set to 12
      min(-1). Nonlinear dynamics were measured as the correlation dimension and the
      nonlinear prediction error. Complexity expressed as correlation dimension was
      unchanged from normal respiration, 9.1 +/- 0.5, compared with forced respiration,
      9.3 +/- 0.6. Also, nonlinear determinism expressed as the nonlinear prediction
      error did not differ between spontaneous respiration, 32.3 +/- 3.4 ms, and forced
      respiration, 31.9 +/- 5.7. It is concluded that the origin of the nonlinear
      dynamics in heart rate variability is not a nonlinear input from the respiration
      into the cardiovascular oscillator. Additional studies are needed to elucidate
      the mechanisms behind the nonlinear dynamics in heart rate variability.

PMID- 9140015
TI  - Obligatory role of NO in glutamate-dependent hyperemia evoked from cerebellar
      parallel fibers.
AB  - Electrical stimulation of cerebellar parallel fibers (PF) increases cerebellar
      blood flow (BFcrb), a response that is attenuated by glutamate receptor
      antagonists and NO synthase (NOS) inhibitors. We investigated whether
      administration of NO donors could counteract attenuation by NOS inhibitors of
      vasodilation produced by PF stimulation. In halothane-anesthetized rats the
      cerebellar cortex was exposed and superfused with Ringer solution. PF were
      stimulated with microelectrodes (100 microA, 30 Hz), and BFcrb was recorded by a
      laser-Doppler probe. During Ringer superfusion, PF stimulation increased BFcrb by
      56 +/- 7% and hypercapnia by 72 +/- 5% (n = 5). Superfusion with the nonselective
      NOS inhibitor N-nitro-L-arginine (L-NNA, 1 mM) reduced resting BFcrb and
      attenuated the response to PF stimulation (-47 +/- 5%) and hypercapnia (-46 +/-
      7%; PCO2 = 50-60 mmHg). After L-NNA, superfusion with the NO donors 3
      morpholinosydnonimine (100 microM, n = 5) or S-nitroso-N-acetyl-penicillamine (5
      microM, n = 5) reestablished resting BFcrb (P > 0.05 vs. before L-NNA) and
      reversed L-NNA-induced attenuation of the response to hypercapnia (P > 0.05 vs.
      before L-NNA) but not PF stimulation (P > 0.05 vs. after L-NNA). Similar results
      were obtained when NOS activity was inhibited with the inhibitor of neuronal NOS
      7-nitroindazole (50 mg/kg i.p.). Like NO donors, the guanosine 3',5'-cyclic
      monophosphate analog 8-bromoguanosine 3',5'-cyclic monophosphate (n = 5),
      administered after L-NNA, restored resting BFcrb and counteracted inhibition of
      the response to hypercapnia but not PF stimulation. In contrast to NO donors and
      8-bromoguanosine 3',5'-cyclic monophosphate, the NO-independent vasodilator
      papaverine (100 microM, n = 5) had no effect on attenuation of responses to PF
      stimulation or hypercapnia. Thus NO donors are unable to reverse the effect of
      NOS inhibition on vasodilation produced by PF stimulation. The data support the
      hypothesis that the vascular response to PF stimulation, at variance with
      hypercapnia, requires NOS activation and NO production. Thus NO plays an
      obligatory role in vasodilation produced by increased functional activity in
      cerebellar cortex.

PMID- 9140016
TI  - Role of nitric oxide in the arterial pressure and renal adaptations to long-term
      changes in sodium intake.
AB  - The goals of this study were to determine whether long-term nitric oxide (NO)
      synthesis inhibition in dogs results in an increase in the sodium sensitivity of
      arterial pressure and whether changes in plasma renin activity or the plasma
      concentrations of arginine vasopressin (AVP) and aldosterone play an important
      role in this hypertension. Studies were conducted in a control group and groups
      that received NO inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) at
      10 or 25 microg x kg(-1) x min(-1). Each group was challenged with normal, low,
      and high sodium intake for periods of 5 days each. Urinary nitrate + nitrite
      excretion (UNOx) more than doubled in the control group during high sodium
      intake. In both L-NAME groups, UNOx decreased significantly, there was a
      hypertensive shift in the relation between urinary sodium excretion and arterial
      pressure, and urinary sodium excretion remained normal even in the high-sodium
      intake period. L-NAME infusion did not change the sodium sensitivity of arterial
      pressure or plasma renin activity, plasma aldosterone, and plasma AVP. In
      conclusion, the data suggest that, in dogs, increases in NO synthesis are not
      necessary to excrete a chronic sodium load, and decreases in NO do not increase
      the sodium sensitivity of arterial pressure.

PMID- 9140017
TI  - Rapid synthesis and secretion of intestinal apolipoprotein A-IV after gastric fat
      loading in rats.
AB  - To further investigate the possible role of apolipoprotein A-IV (apo A-IV) in the
      short-term control of food intake, we examined the kinetics of intestinal apo A
      IV synthesis and release into lymph and plasma after intragastric delivery of
      physiological amounts of lipid. Within 30 min of intragastric administration of
      0.1 g of triglyceride, plasma and lymph levels of apo A-IV were similar to those
      produced by exogenous apo A-IV that inhibit food intake. Within 15 min, 5% of
      gastrically delivered radioactive lipid reached the distal small bowel and cecum;
      by 30 min radioactivity was evenly distributed throughout the small intestine,
      with 10-15% of the load in the distal gut. By 30 min, synthesis of apo A-IV was
      significantly stimulated in proximal and distal jejunum and distal ileum and
      remained elevated up to 4 h after the delivery of lipid. Our results indicate
      that the delivery of physiological amounts of lipid into the stomach produces a
      significant and rapid stimulation of apo A-IV secretion into lymph and plasma,
      together with a rapid delivery of lipid and increases in mucosal synthesis of apo
      A-IV along the entire length of the small intestine. The results support a
      possible role for apo A-IV in the short-term control of food intake and suggest a
      role for the entire gut in the integrative response of apo A-IV to a fat meal.

PMID- 9140018
TI  - Early evening melatonin and S-20098 advance circadian phase and nocturnal
      regulation of core body temperature.
AB  - The phase-shifting capacity and thermoregulatory effects of a single oral
      administration at 18 h of melatonin (5 mg) or S-20098, a melatonin agonist (5 or
      100 mg), was investigated in eight healthy young men in a double-blind placebo
      crossover design. The unmasking conditions of a shortened constant-routine
      protocol (mini-CR) were used to collect evening phase markers of physiological
      parameters. In comparison to placebo, all three drug administrations induced an
      earlier dim-light melatonin onset (DLMO), an earlier increase in distal skin
      temperature, and an earlier decrease in core body temperature (CBT), heart rate,
      and proximal skin temperature. This indicates that administration at 18 h of both
      melatonin and S-20098 (more pronounced with 100 than 5 mg) induced an earlier
      regulation of the endogenous circadian nocturnal decline in CBT. On the
      posttreatment day a second mini-CR revealed persistent significantly phase
      advanced circadian rhythms as estimated by DLMO, as well as by the midrange
      crossing time of CBT and heart rate decline. There were no significant
      differences between the two doses of S-20098. The data suggest that, in addition
      to immediate thermoregulatory changes, a phase advance of the circadian system
      had occurred and that the phase advance could still be measured on the
      posttreatment day.

PMID- 9140019
TI  - Melatonin and S-20098 increase REM sleep and wake-up propensity without modifying
      NREM sleep homeostasis.
AB  - The pineal hormone melatonin has been implicated in the circadian regulation of
      sleep. In a crossover design, we investigated the effect of acute administration
      of 5 mg melatonin and a melatonin agonist (S-20098, 5 and 100 mg) in healthy
      young men when given 5 h before bedtime on sleep structure and
      electroencephalogram (EEG) power density. Each trial comprised a baseline, a
      treatment, and a posttreatment sleep episode. Relative to the placebo condition,
      all treatments phase advanced the core body temperature rhythm [Krauchi, K., C.
      Cajochen, D. Mori, C. Hetsch, and A. Wirz-Justice. Sleep Res. 24: 526, 1995; and
      Krauchi, K., C. Cajochen, D. Mori, and A. Wirz-Justice. Am. J. Physiol. 272
      (Regulatory Integrative Comp. Physiol. 41): R1178-1188, 1997]. Rapid eye movement
      (REM) sleep was increased after both melatonin and S-20098. This increase in REM
      sleep was most pronounced in the first REM sleep episode. On the posttreatment
      night after melatonin and S-20098 administration, more wakefulness was present in
      the latter one-half of the sleep episode. EEG power density between 0.25 and 20
      Hz during either non-REM (NREM) or REM sleep did not differ from placebo. Thus a
      single early evening dose of melatonin or the agonist S-20098 increases REM sleep
      propensity and advances sleep termination while, at the same time, the EEG in
      NREM sleep remains unaffected.

PMID- 9140020
TI  - Sympathetic activation cannot fully account for increased plasma renin levels
      during water deprivation.
AB  - This study was designed to determine if the increase in plasma renin activity
      (PRA) that occurs during water deprivation is mediated by the renal sympathetic
      nerves or adrenomedullary catecholamine release. Male Sprague-Dawley rats were
      studied while conscious and unrestrained. In intact or sham-operated rats, 48 h
      of water deprivation resulted in at least a threefold increase in PRA and plasma
      renin concentration (PRC) but no significant change in plasma norepinephrine or
      epinephrine concentration. Renal denervation decreased basal PRA, reduced the
      magnitude of the dehydration-induced PRA increase by 33%, and abolished the renin
      suppressing effect of l-propranolol infusion in water-deprived rats. Adrenal
      demedullation also reduced basal and water-deprived PRA and PRC. However, even
      the combination of renal denervation and adrenal demedullation did not prevent a
      significant renin response to dehydration (control PRA of 1.8 +/- 0.6 ng x ml(-1)
      x h(-1) to dehydration PRA of 6.8 +/- 1.3 ng x ml(-1) x h(-1), P < 0.05).
      Therefore, some mechanism in addition to sympathoadrenomedullary activation plays
      a major role in mediating increased PRA during water deprivation.

PMID- 9140021
TI  - Leptin increases energy expenditure and selectively promotes fat metabolism in
      ob/ob mice.
AB  - Obesity occurs whenever energy intake exceeds energy expenditure. The ob gene
      product leptin is a potent anorectic agent when administered to ob/ob mice, but
      its effects on energy expenditure have not been investigated in detail. The
      present study was designed to analyze the acute metabolic effects of leptin in
      vivo. Analysis of oxygen consumption in ob/ob mice demonstrated a reduction in
      energy expenditure compared with lean controls; this reduction showed a diurnal
      fluctuation and was most evident during the light cycle. A single intraperitoneal
      dose of leptin increased oxygen consumption during the light cycle in ob/ob mice,
      ablating the circadian fluctuation in this parameter. In addition, leptin had a
      profound effect on fuel selection: the respiratory quotient was markedly reduced,
      indicating a reduction in carbohydrate oxidation and an increase in fat
      oxidation. These acute effects of leptin on metabolic parameters are consistent
      with the selective loss of body fat observed on chronic leptin treatment and
      suggest that increased energy utilization plays an important role in the anti
      obese actions of leptin.

PMID- 9140022
TI  - Sucrose vs. maltose taste discrimination by rats depends on the input of the
      seventh cranial nerve.
AB  - Although rats treat the taste of sucrose and maltose as perceptually similar,
      they nonetheless appear to be able to distinguish between the two sugars, as
      suggested from prior work examining the cross-generalization of conditioned taste
      aversions. This study explictly tested whether rats could behaviorally
      discriminate sucrose from maltose and examined the relative importance of the
      gustatory input of the seventh and ninth cranial nerves in maintaining such
      performance. Water-restricted rats were presurgically trained in a conditioned
      avoidance task to suppress licking to sucrose or maltose and to maintain licking
      to the other sugar. Concentration (0.05, 0.1, 0.2, and 0.4 M) was varied to make
      intensity an irrelevant cue. Stimuli were randomly presented in 5-s trials during
      50-min sessions. Bilateral transection of the chorda tympani nerve (CT) or the
      glossopharyngeal nerve or sham surgery did not disrupt discrimination
      performance. In contrast, combined transection of the CT and greater superficial
      petrosal nerve, which collectively removes the taste input of the seventh cranial
      nerve, caused severe impairments in sugar discriminability. In these rats,
      performance was more disturbed at the lower concentrations. These findings
      confirm that rats can discriminate sucrose from maltose and that this capability
      relies heavily on the taste input of the seventh cranial nerve. Although the
      input of the ninth cranial nerve is unnecessary, it may help sustain partial
      competence in this task, especially at high concentrations, in the combined
      absence of the CT and greater superficial petrosal nerve.

PMID- 9140023
TI  - Aging and photoperiod affect entrainment and quantitative aspects of locomotor
      behavior in Syrian hamsters.
AB  - Aging affects the regulation of diurnal and circadian rhythmicity. We tested the
      hypothesis that the age-related difference in the phase angle of entrainment of
      the locomotor activity rhythm to a light-dark (LD) cycle would be greater under
      LD 6:18 than LD 14:10. We also analyzed changes in quantitative aspects of wheel
      running behavior according to age group. Young (9-wk-old), middle-aged (11- to 12
      mo-old), and old (15- to 17-mo-old) male golden hamsters were entrained to a
      14:10 LD cycle followed by re-entrainment to a 6:18 LD cycle. Fourteen days after
      the start of locomotor recording in LD 14:10 and again after 27 days in LD 6:18,
      the phase of activity onset, the total number of wheel revolutions performed per
      day, the peak intensity of wheel-running activity, the duration of the active
      period, and the level of fragmentation of locomotor activity were quantitated. We
      also studied the temporal distribution of the largest bout of wheel-running
      activity among the age groups in both photoperiods. Short days induced testicular
      regression at a similar rate among young, middle-aged, and old hamsters. The data
      are discussed in terms of the effects of age on overall circadian organization in
      the seasonally changing environment.

PMID- 9140024
TI  - Symmetric pH dependence of buffering power in giant fused cells from frog kidney
      proximal tubule.
AB  - This study measures the intrinsic buffering power (beta(i)) of giant fused cells
      from the proximal kidney tubule of the frog (Rana ridibunda) as a function of
      intracellular pH (pHi). We monitored pHi and transmembrane potential difference
      during acid or alkaline cell loading, achieved by removal of NH4Cl-containing
      solutions or CO2-HCO3(-)-equilibrated solutions, respectively, in the absence of
      extracellular Na+. Data were well fit by the equation for a single, monoprotic
      buffer with a maximum beta(i) at a pHi of 7.39 +/- 0.06 and a total buffer
      concentration of 30.7 +/- 1.6 mM (means +/- SD). From pHi measurements obtained
      during CO2-HCO3- exposure, we also calculated the buffering power afforded by the
      CO2-HCO3- pair, and we show its increasing contribution to total buffering power
      at increasing PCO2 and pHi. To our knowledge, this is the first report of a cell
      type in which intrinsic cell buffers can be adequately approximated as a single
      monoprotic buffer with a negative logarithm of apparent dissociation constant in
      the normal physiological range and essentially symmetric dependence on pHi in
      both acid and alkaline ranges.

PMID- 9140025
TI  - Rates of local cerebral protein synthesis in fetal and neonatal sheep.
AB  - During gestation there is likely to be a constantly changing rate of protein
      synthesis in the brain that may exhibit regional specificity. With the use of the
      quantitative autoradiographic L-[1-(14)C]leucine method for the determination of
      local rates of leucine incorporation into cerebral protein (lCPS(Leu)), we have
      sought to characterize this important process. lCPS(Leu) was measured in nine
      fetal sheep (118-139 days gestational age) and five newborn lambs (1-5 days of
      age). In other experiments, the fraction of leucine in the precursor pool for
      protein synthesis in the brain derived from the arterial plasma was determined to
      be 0.57 +/- 0.04 (mean +/- SE) in one fetus and two lambs. This value was used in
      the calculation of lCPS(Leu) in 35 regions of the central nervous system, pineal
      body, and whole brain. Regardless of age, lCPS(Leu) was highest in the pineal
      body, brain stem, and hypothalamic nuclei and lowest in white matter. In
      sensorimotor cortex, corona radiata, pyramidal tracts, and whole brain, lCPS(Leu)
      was positively correlated with prenatal age (P < or = 0.05). These increases in
      lCPS(Leu) probably reflect myelination in the cerebrum, which is known to occur
      in late gestation.

PMID- 9140026
TI  - Vagal afferent and efferent contributions to the inhibition of food intake by
      cholecystokinin.
AB  - To assess the role of subdiaphragmatic vagal afferent and efferent fibers in the
      mediation of the inhibition of food intake by cholecystokinin (CCK), we compared
      the ability of a dose range (1-16 microg/kg), of CCK to affect 30-min liquid
      glucose (0.125 g/ml) intake in rats with either total subdiaphragmatic vagotomy,
      selective subdiaphragmatic vagal deafferentation, selective subdiaphragmatic
      vagal deefferentation, or sham surgery. Selective vagal deafferentation and
      deefferentations were produced by combinations of unilateral subdiaphragmatic
      vagotomy and contralateral afferent or efferent rootlet transection as fibers
      enter the caudal medulla. CCK produced a dose-related suppression of glucose
      intake in sham animals, and this action was eliminated in rats with total
      subdiaphragmatic vagotomy. CCK suppression of intake was attenuated in rats with
      vagal deafferentation, such that there was a loss of sensitivity to CCK. Vagal
      deefferentation resulted in lower levels of baseline intake and a truncation of
      the feeding-inhibitory actions of CCK. These data demonstrate that CCK's
      suppression of intake depends on actions of both vagal afferent and efferent
      fibers. We interpret these data as suggesting that 1) the actions of low doses of
      CCK depend on activation of vagal afferent CCK receptors and 2) the greater
      efficacy of higher CCK doses is the result of the potentiation of these vagal
      afferent actions due to local physiological gastrointestinal effects of the
      peptide that rely on vagal efferent input.

PMID- 9140027
TI  - Individual differences in response to LPS and psychological stress in aged rats.
AB  - Old rats may show blunted fever or hypothermia after injection of
      lipopolysaccharide (LPS), a fever-producing agent, and have a reduced body
      temperature (Tb) rise in response to psychological stress. These results may
      partly be a consequence of aging per se, partly a sex difference, and partly an
      effect of differences in types and doses of pyrogen. Here we tested age and
      gender differences in Tb responses to 30-min exposure to a novel environment and
      to injection of several doses of LPS. There were age-related reductions in
      novelty-induced hyperthermia, and some old rats even became hypothermic.
      Sensitivity to the pyrogenic activity of LPS and to the toxic effects of
      endotoxin (manifested by hypothermia) both increased in aged female rats. A major
      finding was that there were no correlations between age-related changes in Tb in
      response to novelty and to LPS injection. Tb responses in aged rats were
      variable; in each situation, there were old rats whose Tb rose as high as did
      younger ones. We did not observe significant gender differences in response
      either to novelty or to LPS in young or old rats.

PMID- 9140028
TI  - Antioxidant status and lipid peroxidation after short-term maximal exercise in
      trained and untrained humans.
AB  - The purpose of this study was to measure resting muscle and blood antioxidant
      status in untrained (n = 8) and jump-trained (n = 8) humans and to evaluate free
      radical-mediated muscle damage after a strenuous jump test consisting of six
      bouts of 30-s continuous jumping separated by 2 min of rest. Resting muscle
      antioxidant activities [superoxide dismutase (SOD), glutathione peroxidase (GPX),
      glutathione reductase (GR), and manganese SOD] were significantly higher in jump
      trained compared with untrained subjects. Blood antioxidant enzyme activities and
      muscle catalase, however, were not different between the two groups. Creatine
      kinase activities increased significantly (P < 0.0001) after the jump test in
      untrained individuals, but remained unchanged in the jump trained. Plasma and
      muscle malonaldehyde (MDA) after the jump test were not significantly different
      from rest. These data suggest that jump training is associated with elevated
      activities of SOD and the coupled enzymes GPX and GR in muscle tissue, but other
      antioxidants remain unchanged. High-intensity jump exercise induces muscle enzyme
      leakage in untrained humans, but muscle lipid peroxidation, measured as changes
      in MDA, was not different in the two groups despite the varied muscle antioxidant
      enzyme levels.

PMID- 9140029
TI  - Reduced insulin suppression of glucose appearance is related to susceptibility to
      dietary obesity in rats.
AB  - To examine the relationship between insulin action and body weight regulation in
      male rats, the following studies were performed. In study 1, rats (n = 31) were
      fed a low-fat diet (LFD) for 4 wk, and then glucose kinetics were estimated under
      basal and hyperinsulinemic conditions using the glucose clamp. After clamps,
      these same rats were placed on a high-fat diet (HFD) for 5 wk. In study 2, rats
      (n = 30) were fed an LFD for 3 wk and then a high-sucrose diet for 1 wk to
      produce selective hepatic insulin resistance. Clamps were then performed, and
      after clamps, these same rats were placed on an HFD for 5 wk. In study 3, rats (n
      = 30) were fed an LFD for 1 wk and then a high-sucrose diet for 3 wk to produce
      widespread insulin resistance. Clamps were then performed, and after clamps,
      these same rats were placed on an HFD for 5 wk. The rate of glucose appearance
      (R(a)) during the hyperinsulinemic clamps was the only pre-HFD variable that
      correlated (r = 0.49, P < 0.01 in study 1; r = 0.51, P < 0.001 in study 2) with
      weight gain on the HFD. Clamp R(a) also correlated with energy intake on the HFD
      in study 1 (r = 0.64, P < 0.001) and study 2 (r = 0.59, P < 0.001). Clamp R(a)
      and energy intake on the HFD accounted for similar portions of the variance in
      body weight gain on the HFD. Weight gain and fat-pad mass were increased (P <
      0.05) in study 2 compared with study 1. In study 3, pre-HFD glucose kinetics were
      not correlated with energy intake or weight gain on the HFD. Widespread insulin
      resistance did not significantly reduce the rate of weight gain on the HFD. Thus
      insulin action on R(a) can influence body weight gain on an HFD. The effects of
      R(a) on body weight gain appear to be mediated via effects on energy intake.
      Selective hepatic insulin resistance can increase body weight gain on an HFD, but
      widespread insulin resistance does not significantly reduce HFD-induced weight
      gain.

PMID- 9140030
TI  - Detrusor-sphincter dyssynergia induced by cold stimulation of the urinary bladder
      of rats.
AB  - Instillation of cold water into the urinary bladder has been used as a diagnostic
      test to evaluate neurogenic dysfunctions of the lower urinary tract (LUT). This
      study examined the effects of cold stimulation on the LUT of urethan-anesthetized
      rats. Urinary bladder pressure and external urethral sphincter (EUS)
      electromyogram (EMG) were recorded during cystometrograms in which body- or room
      temperature saline was infused continuously into the bladder and voided through
      the urethra. Subsequent infusion of cold saline (6-8 degrees C) into the bladder
      increased by approximately 100% the duration and amplitude of supraspinal reflex
      bladder contractions, increased baseline bladder pressure, increased the pressure
      threshold for inducing micturition, and increased EUS EMG activity. Blocking EUS
      activity by transecting the pudendal nerves or by administering a neuromuscular
      blocking agent markedly reduced or eliminated the effect of cold stimulation.
      Capsaicin pretreatment suppressed the effect of cold stimulation. It is concluded
      that cold temperatures stimulate capsaicin-sensitive C fiber bladder afferents
      that reflexly activate the EUS, producing detrusor and sphincter dyssynergia and
      increasing urethral outlet resistance. This in turn increases the amplitude and
      duration of bladder contractions during voiding.

PMID- 9140031
TI  - Preoptic recess alpha-adrenoceptors control cardiovascular responses to
      hyperosmolality.
AB  - The roles of alpha-adrenoceptors in the anteroventral third ventricle (AV3V) and
      diagonal band of Broca (DBB) in cardiovascular responses to peripheral
      hypertonicity were investigated in conscious rats. Normal artificial
      cerebrospinal fluid (aCSF) or aCSF containing phentolamine (alpha1- and alpha2
      antagonist), yohimbine (alpha2-antagonist), or prazosin (alpha1-antagonist) was
      perfused through microdialysis probes in the DBB, AV3V, or lateral ventricle
      during a 30-min infusion of isotonic (0.17 M; 0.1 or 1.7 ml x kg(-1) x min(-1)
      i.v.) or hypertonic (2.5 M; 0.1 ml x kg(-1) x min(-1) i.v.) NaCl. Hypertonic
      infusion increased blood pressure [mean arterial blood pressure (MAP); 17 +/- 2
      mmHg] and decreased heart rate (HR; 36 +/- 6 beats/min). Both responses were
      abolished by AV3V administration of phentolamine or yohimbine, whereas prazosin
      selectively prevented the bradycardia. Phentolamine in the DBB or lateral
      ventricle did not alter either response. Stimulation of AV3V alpha1-adrenoceptors
      (phenylephrine) decreased HR and MAP, whereas alpha2-adrenoceptor stimulation
      (clonidine) produced bradycardia but increased MAP. Data suggest that alpha
      adrenoceptors in the AV3V, but not the DBB, regulate cardiovascular responses to
      hyperosmolality.

PMID- 9140032
TI  - Role of ET(A) and ET(B) receptors in endothelin-1-induced adrenal catecholamine
      secretion in vivo.
AB  - The present study was designed to test whether endothelin (ET) A and/or B
      receptors in the adrenal medulla are functionally involved in ET-1-induced
      catecholamine (CA) release in anesthetized dogs. ET-1 was locally infused into
      the gland via the left adrenolumbar artery. Plasma CA in adrenal venous and
      aortic blood was determined by a high-performance liquid chromatography method.
      In the control group, the local infusion of ET-1 (0.5 microg, 0.4 microM)
      resulted in a significant increase in CA output. In the presence of a low dose of
      BQ-123 (5 microg, 16.4 microM), the ET-1-induced CA response was significantly
      attenuated by approximately 80%. With a high dose of BQ-123 (50 microg, 164
      microM), the CA response was further blocked by approximately 95%. This
      inhibition was significantly greater than that obtained with the low dose of BQ
      123. By contrast, a low dose of BQ-788 (5 microg, 15.1 microM) did not
      significantly affect the CA response. With a high dose of BQ-788 (50 microg, 151
      microM), the CA response was only partially inhibited by approximately 70%. The
      results indicate that BQ-123 significantly inhibited ET-1-induced adrenal CA
      release in a dose-dependent manner. With the low doses, the CA response was
      markedly inhibited by BQ-123 but remained unchanged in the presence of BQ-788.
      Moreover, the high dose of BQ-123 virtually abolished the CA response, whereas BQ
      788 failed to do so within the dose range tested. The present study suggests that
      the ET(A) receptor may play a predominant role in mediating the ET-1-induced CA
      secretion in the canine adrenal gland in vivo, although the possible involvement
      of the ET(B) receptor could not completely be excluded under the present
      experimental conditions.

PMID- 9140034
TI  - Brown fat thermogenesis and cardiac rate regulation during cold challenge in
      infant rats.
AB  - Infants rats depend on heat production by brown adipose tissue (BAT) during cold
      challenge. Although it has been suggested that BAT thermogenesis protects the
      heart in the cold, the relationship of BAT activation to cardiac rate has not
      been examined directly. In the first experiment, the cardiac rate of 2- and 7- to
      8-day-old rat pups was monitored during moderate and extreme cold challenge. Pups
      at both ages maintained cardiac rate during moderate cold challenge while BAT
      thermogenesis was increasing. In contrast, cooling to air temperatures at which
      BAT thermogenesis could increase no further resulted in pronounced bradycardia.
      In the second experiment, ganglionic blockade was used to eliminate BAT heat
      production and autonomic control of the heart in 7- to 8-day olds. Blockade
      suppressed BAT thermogenesis in the cold and led to pronounced decreases in
      interscapular temperature and cardiac rate. These data suggest that cardiac rate
      in infant rats is modulated both by the autonomic nervous system and BAT
      thermogenesis.

PMID- 9140033
TI  - Dietary n-3 fatty acids differentially affect sickness behavior in mice during
      local and systemic inflammation.
AB  - We tested the hypothesis that increased dietary fish oil levels (via modulation
      of the production of inflammatory mediators) modulate sickness symptoms (i.e.,
      anorexia, cachexia, fever, lethargy) of systemic and local inflammation. Swiss
      Webster mice were implanted with biotelemeters to measure body temperature and
      motor activity and were fed a diet high in n-3 fatty acids (17% wt/wt menhaden
      oil) or a reference diet (17% wt/wt hydrogenated coconut oil or normal rodent
      chow) for 6 wk. Local inflammation was induced by subcutaneous injection of
      turpentine (100 microl/mouse). Systemic inflammation was elicited by
      intraperitoneal injection of lipopolysaccharide (LPS; 2.5 mg/kg). Fever,
      lethargy, anorexia, and weight decrease during turpentine abscess were all
      inhibited (P < 0.05) in mice fed the fish oil diet. Indomethacin, similar to the
      fish oil diet, attenuated the turpentine-induced symptoms in mice fed a normal
      diet. Dietary n-3 fatty acids prevented fever and attenuated the decrease in body
      weight caused by LPS but did not affect the LPS-induced lethargy and anorexia.
      Within 90 min of LPS injection, the bioactivity of plasma tumor necrosis factor
      alpha (TNF-alpha) increased to 98.2 +/- 5.1 ng/ml in mice fed fish oil compared
      with 32.6 +/- 3.6 ng/ml in those fed the reference diet (P < 0.05). Plasma
      prostaglandin E2 (PGE2) levels after LPS injection of mice fed the control diet
      increased within 90 min to 16.4 +/- 5.1 pg/ml. Mice fed the fish oil diet did not
      show any elevation in plasma PGE2 levels at that time (P < 0.05). We speculate
      that dietary n-3 fatty acids suppressed PGE2-related responses, including a PGE2
      dependent negative feedback on TNF-alpha production, which resulted in
      differential modulation of sickness behavior depending on the locus of
      inflammation.

PMID- 9140035
TI  - Coupled oscillators account for the slow rhythms in sympathetic nerve discharge
      and phrenic nerve activity.
AB  - Phase-locked slow rhythms in sympathetic nerve discharge (SND) and phrenic nerve
      activity (PNA) are generally thought to arise from a common brain stem
      "cardiorespiratory" oscillator. The results obtained in vagotomized and
      baroreceptor-denervated cats anesthetized with pentobarbital sodium do not
      support this view. First, partial coherence analysis revealed that the discharges
      of pairs of sympathetic nerves remained correlated at the frequency of the
      central respiratory cycle after mathematical removal of the portion of these
      signals common to PNA. The residual coherence suggests that the slow rhythm in
      SND is dependent on central mechanisms in addition to those responsible for
      rhythmic PNA. Second, the rhythms in SND and PNA became coupled in a 2:1
      relationship during either moderate systemic hypocapnia or hypercapnia. Third,
      the slow rhythm in SND was maintained when rhythmic PNA was eliminated during
      extreme hypocapnia. Fourth, during extreme hypercapnia, coherence of the rhythms
      in SND and PNA was drastically reduced. These results suggest that the slow
      rhythms in SND and PNA arise from separate oscillators that are normally coupled.

PMID- 9140036
TI  - Inhibition of tumor necrosis factor prevents warming-induced sleep responses in
      rabbits.
AB  - Tumor necrosis factor (TNF) is a key regulatory component of sleep. In the
      present study, we determined the effects of intracerebroventricular injection of
      a TNF inhibitor, a soluble TNF receptor fragment (TNF-RF), on sleep responses of
      rabbits during and after exposure to mild increases in ambient temperature
      (T(amb)). Each rabbit (n = 8) was recorded under three conditions: 1) normal
      T(amb) (21 degrees C) with pyrogen-free saline (PFS), 50 microl i.c.v.; 2) 27
      degrees C T(amb) with PFS, intracerebroventricularly; and 3) 27 degrees C T(amb)
      with the TNF-RF, 50 microg i.c.v. When T(amb) was increased to 27 degrees C from
      21 degrees C, it was kept at that temperature for 6 h after injection. The higher
      T(amb) alone significantly increased non-rapid eye movement sleep, decreased
      rapid eye movement sleep, and increased brain temperature (T(br)) across the 23-h
      recording period. Electroencephalogram slow-wave activity was also significantly
      enhanced during the 6-h warming period. In contrast, all of the sleep responses
      associated with the higher T(amb) were absent if rabbits were pretreated with the
      TNF-RF. The elevated T(br) during the higher T(amb) was not affected by the TNF
      RF. The present results suggest that brain TNF is involved in the mild increases
      in T(amb)-induced sleep responses.

PMID- 9140038
TI  - Energy budget in free-living animals: a novel approach based on the doubly
      labeled water method.
AB  - We provide a theoretical and practical model for the calculation of energy
      balance of free-living animals using the doubly labeled water method. Energy
      expenditure, metabolizable energy intake, and body energy balance (energy
      retention, negative or positive) of animals are estimated using CO2 production,
      water influx, and dietary habits. This model accounts for CO2 produced from the
      1) oxidation of dietary substrates, 2) catabolism of body tissue, and 3)
      deposition of body energy. We examined the model using data from studies on five
      homeotherms reported in the literature. The ratios between daily energy
      expenditure using our model and that presented in the reports ranged between 0.76
      and 1.18. Metabolizable energy intakes were as low as 43% of energy expenditure
      in negative energy-balanced hummingbirds and as high as 245% of energy
      expenditure in positive energy-balanced koala bears. This model is the first that
      allows theoretical calculation of all energy budget components, including energy
      retention, in free-living animals using the doubly labeled water method.

PMID- 9140037
TI  - Hexose transport across the basolateral membrane of the chicken jejunum.
AB  - The characteristics of the basolateral transport of D-glucose (D-Glc) and D
      fructose (D-Fru) have been studied in membrane vesicles from the jejunum of 5- to
      6-wk-old chickens. Uptake of hexoses was measured using a rapid filtration
      method. The maximal rate of transport (Vmax) for D-Glc was 2.36 nmol x mg(-1) x
      s(-1) and for D-Fru was 3.79 nmol x mg(-1) x s(-1). The Michaelis constants were
      17.3 mmol/l for D-Glc and 40.4 mmol/l for D-Fru. D-Glc inhibited its own
      transport (Ki = 17.4 mmol/l) and the transport of D-Fru (Ki = 18.7 mmol/l). D-Fru
      inhibited its own transport (Ki = 38.1 mmol/l) and the transport of D-Glc (Ki =
      40.3 mmol/l). The transport of both hexoses was Na+ independent, theophylline and
      cytochalasin B sensitive, and showed cis-inhibition by structural analogs. In
      preloaded vesicles, the uptake of D-Fru was trans-stimulated by D-Glc and 2-deoxy
      D-glucose. These properties indicate the presence of a low-affinity high-capacity
      glucose transporter isoform (GLUT-2)-type carrier in the chicken intestine,
      responsible for moving both D-Glc and D-Fru across the basolateral membrane.

PMID- 9140039
TI  - Comparison of ANP binding and sensitivity in brains from hypertensive and
      normotensive rats.
AB  - We compared the abundance and sensitivity of atrial natriuretic peptides (ANP)
      receptors in the brains of spontaneously hypertensive (SHR) and Wistar-Kyoto
      (WKY) rats and examined the effect of blood pressure on the abundance of brain
      ANP receptors in several other experimental rat models. Brain slices from SHR
      generated more guanosine 3',5'-cyclic monophosphate in response to ANP than brain
      slices from WKY rats. No differences were found in brain particulate guanylate
      cyclase activity in both strains of rats. In rat brain homogenates, we observed
      that ANP bound in a specific and saturable fashion to samples from WKY rats, but
      not in samples from SHR. In vitro receptor autoradiography revealed that ANP
      binding was reduced in the subfornical organ, the choroid plexus, and the
      paraventricular nucleus of SHR compared with WKY rat brains. Correction of
      hypertension in SHR or induction of hypertension in other strains did not affect
      ANP binding in any of these brain regions. Altogether, our data suggest that the
      increased sensitivity of SHR brains to the action of ANP may be a consequence of
      factors other than the abundance of receptors and that it is not secondary to the
      elevation of blood pressure.

PMID- 9140040
TI  - Leptin facilitates and inhibits sexual behavior in female hamsters.
AB  - Food deprivation decreases fertility in female mammals in part by inhibiting
      sexual behaviors. Genetically obese ob/ob mice, like food-deprived wild-type
      animals, are also infertile; treatment of ob/ob mice with leptin, the adipocyte
      derived protein that they lack, corrects some of their reproductive deficiencies.
      We tested the hypothesis that leptin treatment would prevent the suppression of
      sexual receptivity that is caused by food deprivation in female Syrian hamsters.
      Instead, we found that treatment with murine leptin facilitated female sexual
      behavior in ad libitum-fed hamsters, but not in food-deprived animals. In food
      deprived hamsters, leptin treatment actually intensified the inhibition of
      lordosis. Food deprivation decreased detectable estrogen receptor
      immunoreactivity (ERIR) in the ventromedial hypothalamus (VMH), but the leptin
      induced changes in female sexual behavior were not accompanied by parallel
      changes in VMH ERIR. Thus leptin facilitates estrous behavior in hamsters, but it
      does not overcome the lordosis-inhibiting metabolic cues produced by acute food
      deprivation. Because circulating leptin levels are directly related to body fat
      content, an implication of these findings is that elevated levels of adipose
      tissue could have a positive influence on sexual responsiveness.

PMID- 9140041
TI  - Membrane polarity in epithelial cells: protein sorting and establishment of
      polarized domains.
AB  - Epithelial cells go to great trouble to organize the subdomains of their plasma
      membranes. The apical and basolateral surfaces of polarized epithelia are
      equipped with markedly distinct populations of channels, carriers, and pumps.
      This anisotropy is an absolute prerequisite for vectorial solute and fluid
      transport. The physiological properties of an individual epithelial cell type are
      determined not only by its census of transport proteins but also by the manner in
      which these proteins are segregated between the apical and basolateral portions
      of the plasmalemma (Curr. Top. Membr. 39: 37-86, 1991). To achieve this
      asymmetry, an epithelial cell must be able to establish distinct surface domains,
      to target newly synthesized transport proteins to their appropriate sites of
      functional residence, and to retain them there following their delivery. Studies
      of the cellular pathways involved in generating and maintaining the polarized
      state have begun to illuminate an elegant network of cell biological
      specializations that may be involved not only in establishing the distributions
      of transport proteins but in dynamically regulating their function as well.

PMID- 9140042
TI  - Putting the actin cytoskeleton into perspective: pathophysiology of ischemic
      alterations.
AB  - The actin cytoskeleton plays an ever-increasingly understood role in mediating a
      myriad of processes necessary for cellular structure and function. New and
      exciting information regarding the dynamic aspects of the actin cytoskeleton and
      its intracellular regulation are unfolding at a rapid rate. Actin cytoskeletal
      surface membrane interactions mediating such diverse cellular events as cell
      polarity, endocytosis, exocytosis, cell division, cellular migration, cell
      adhesion, signal transduction, and ion channel activity are part of an ever
      growing list of cellular processes dependent on precise actin polarization and
      regulation of assembly and disassembly. The purpose of this review is to
      highlight recent advances in the understanding of actin cytoskeleton-mediated
      cellular processes, to provide a framework that interrelates the complex protein
      protein interactions necessary for localization, regulation, and mediation of
      these essential cellular functions, and to outline the role of actin effector
      proteins in the pathophysiology of ischemic cell injury.

PMID- 9140043
TI  - Epithelial cell polarity and disease.
AB  - The establishment and maintenance of epithelial polarity is essential for the
      integrity and function of epithelial organs and is particularly critical in the
      kidney, where vectorial reabsorption and secretion are effected in different
      segments of the nephron by the differential polarized insertion of channels,
      transporters, and related proteins into apical membranes lining the tubule lumen
      or basolateral membranes adjacent to the interstitium and blood space. Faulty
      intracellular delivery and polarization of membrane proteins can lead to serious
      diseases such as cystic fibrosis, I cell disease, and renal cystic diseases. The
      best understood disease of epithelial polarity is autosomal dominant polycystic
      kidney disease (ADPKD) caused by mutations in a >462-kDa, developmentally
      regulated membrane protein, "polycystin." ADPKD cysts are characteristically
      lined by a single layer of structurally polarized epithelial cells with normal
      functional intercellular tight junctions but with aberrant polarization of some
      important membrane proteins. Abnormal apical membrane polarity of biochemically
      active, ouabain-sensitive Na-K-adenosinetriphosphatase (Na-K-ATPase) in ADPKD
      cyst epithelia leads to abnormal sodium ion secretion and provides a mechanism
      for aberrant fluid secretion. In addition, apically mislocated, functional
      epidermal growth factor (EGF) receptors on cyst epithelia, together with EGF
      synthesis and secretion into cyst lumens, provide a mechanism for autocrine
      regulation of increased epithelial cell proliferation in ADPKD. Underlying
      mechanisms for these abnormalities in polarized distribution of membrane proteins
      include the aberrant expression of fetal gene products, such as the beta2-subunit
      of Na-K-ATPase, in ADPKD kidneys. Overexpression of polycystin protein in ADPKD
      cyst epithelia, low levels restricted to medullary collecting tubules in normal
      adult kidneys, and high levels in ureteric bud-derived structures in human fetal
      kidneys further suggest a failure of downregulation of fetal genes as a mechanism
      for the polarity abnormalities that characterize ADPKD.

PMID- 9140044
TI  - Adenylate cyclase-coupled vasopressin receptor activates AQP2 promoter via a dual
      effect on CRE and AP1 elements.
AB  - Vasopressin plays an essential role for the regulation of water balance by
      activating the collecting duct-specific water channel, aquaporin-2 (AQP2). Here
      we present evidence that vasopressin may also act as a long-term, transcriptional
      regulator of AQP2. The studies were performed on LLC-PK1 cells, which normally
      express V2 receptor (V2R) and which were transfected with a fragment of the human
      AQP2 promoter. Activation of the adenylate cyclase-coupled V2R in LLC-PK1 cells
      induced phosphorylation of adenosine 3',5'-cyclic monophosphate (cAMP) responsive
      element binding protein (CREB) and expression of c-Fos. Binding of these factors
      to the CRE and AP1 site did, in combination, lead to AQP2 promoter activation.
      These results establish the role of vasopressin as a regulator of transcription
      and are the first example of how a message from a highly specific receptor is,
      via a dual effect of the cAMP signal on CREB and immediate early gene expression,
      transduced to the transcription of a final target protein with known biological
      effects.

PMID- 9140045
TI  - Distribution and developmentally regulated expression of murine polycystin.
AB  - PKD1, the gene that is mutated in approximately 85% of autosomal dominant
      polycystic kidney disease (ADPKD) cases in humans, has recently been identified
      (Eur. PKD Consortium. Cell 77: 881-894, 1994; also, erratum in Cell 78: 1994).
      The longest open-reading frame of PKD1 encodes polycystin, a novel approximately
      460-kDa protein that contains a series of NH2-terminal adhesive domains (J.
      Hughes, C. J. Ward, B. Peral, R. Aspinwall, K. Clark, J. San Millan, V. Gamble,
      and P. C. Harris. Nat. Genet. 10: 151-160, 1995; and Int. PKD Consortium. Cell
      81: 289-298, 1995) and several putative transmembrane segments. To extend studies
      of polycystin to an experimentally accessible animal, we have isolated a cDNA
      clone encoding the 3' end of Pkd1, the mouse homologue of PKD1, and raised a
      specific antibody to recombinant murine polycystin. This antibody was used to
      determine the subcellular localization and tissue distribution of the protein by
      Western analysis and immunocytochemistry. In the mouse, polycystin is an
      approximately 400-kDa molecule that is predominantly found in membrane fractions
      of tissue and cell extracts. It is expressed in many tissues including kidney,
      liver, pancreas, heart, intestine, lung, and brain. Renal expression, which is
      confined to tubular epithelia, is highest in late fetal and early neonatal life
      and drops 20-fold by the third postnatal week, maintaining this level into
      adulthood. Thus the temporal profile of polycystin expression coincides with
      kidney tubule differentiation and maturation.

PMID- 9140046
TI  - Localization of cyclooxygenase-1 and -2 in adult and fetal human kidney:
      implication for renal function.
AB  - To gain insight into the roles of cyclooxygenase (COX)-1 and -2 in human kidney,
      we analyzed their expressions and localization in adult and fetal normal kidney.
      Immunohistology showed expression of COX-1 in collecting duct cells, interstitial
      cells, endothelial cells, and smooth muscle cells of pre- and postglomerular
      vessels. Expression of COX-2 immunoreactive protein could be localized to
      endothelial and smooth muscle cells of arteries and veins and intraglomerularly
      in podocytes. In contrast to the rat, COX isoforms were not detected in the
      macula densa. These data were confirmed by in situ mRNA analysis using
      digoxigenin-labeled riboprobes. In fetal kidney, COX-1 was primarily expressed in
      podocytes and collecting duct cells. Expression levels of COX-1 in both cell
      types increased markedly from subcapsular to juxtamedullary cortex. Glomerular
      staining of COX-2 was detectable in podocytes only at the endstage of renal
      development. In summary, the localization of COX-2 suggests that this enzyme may
      be primarily involved in the regulation of renal perfusion and glomerular
      hemodynamics. The expression of COX-1 in podocytes of the fetal kidney and its
      absence in adult glomeruli suggests that this isoform might be involved in
      glomerulogenesis.

PMID- 9140047
TI  - Metanephric osteopontin regulates nephrogenesis in vitro.
AB  - Renal expression of osteopontin is enhanced in the setting of acute ischemic
      injury. Because of the parallels that exist between recovery from renal ischemia
      and renal development, we characterized the role that osteopontin plays during
      metanephrogenesis in the rat. Osteopontin mRNA is present in kidneys obtained
      from rat embryos as early as embryonic day 13 (E13). Immunohistochemical staining
      of metanephroi obtained from E16 rat embryos and metanephroi obtained from E13
      embryos and cultured for 3 days in vitro demonstrated that osteopontin is
      expressed both in the developing nephron and in the ureteric bud. Addition of
      anti-osteopontin antibodies to metanephric organ cultures results in failure of
      the metanephric blastema to undergo normal tubulogenesis. Addition of the
      arginine-glycine-aspartic acid-containing peptide, cyclo-RGDfV, or the anti
      alpha(v)beta3-integrin antibody, LM609, to cultures has a similar effect. These
      findings establish that osteopontin is produced within the rat metanephros during
      development in vivo and suggest that the binding of osteopontin to the
      alpha(v)beta3-integrin is required for tubulogenesis to occur in vitro. Blastemal
      cells within metanephroi cultured in the presence of OP199 manifest increased
      apoptosis compared with controls. It is possible that osteopontin plays an
      important anti-apoptotic role during the process of metanephric blastema
      condensation that is a prerequisite for the formation of nephrons in vivo.

PMID- 9140049
TI  - Insulin-like growth factor I stimulates apical sodium/hydrogen exchange in human
      proximal tubule cells.
AB  - To determine whether insulin-like growth factor I (IGF-I) stimulated apical
      sodium/hydrogen exchange (NHE), confluent primary human proximal tubule cells
      (PTC) were incubated for 48 h in serum-free media in the presence or absence of
      100 ng/ml IGF-I. Cells incubated in IGF-I demonstrated significant increases in
      thymidine incorporation (181.2 +/- 30.3% of control values; n = 12, P = 0.01) and
      in resting intracellular pH (pHi) (7.52 +/- 0.08 vs. 7.30 +/- 0.06; n = 20, P <
      0.05), as determined by 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein
      quantitative microspectrofluorometry. Following intracellular acid loading,
      ethylisopropylamiloride (EIPA)-inhibitable H+ efflux and 22Na+ influx after 1 min
      were both significantly enhanced in IGF-I-treated cells compared with controls
      (8.78 +/- 1.69 vs. 3.03 +/- 0.72 mM/min and 3.47 +/- 0.49 vs. 1.55 +/- 0.35 nmol
      x mg protein(-1) x min(-1), respectively). 22Na+ uptake studies in PTC grown on
      permeable supports demonstrated preferential stimulation of apical vs.
      basolateral NHE. The 50% inhibitory concentrations (IC50) in IGF-I-treated and
      control cells for EIPA (0.5 and 1.1 microM, respectively) and for HOE-694 (4.0
      and 10.0 microM, respectively) were also consistent with predominant activation
      of apical, rather than basolateral, NHE activity. Kinetic analysis revealed an
      increase in maximal transport velocity (Vmax, 15.50 +/- 1.50 vs. 7.26 +/- 3.07
      mM/min; n = 10, P < 0.05), without a significant change in antiporter affinity
      for extracellular Na+. Incubation of PTC with 100 ng/ml IGF-I produced an acute,
      reversible, and EIPA-inhibitable pHi increase of 0.05 +/- 0.01 pH units (n = 5, P
      < 0.05). The results suggest that IGF-I may contribute to the metachronous
      stimulation of apical NHE and PTC growth observed in many physiological and
      pathological conditions involving the human kidney.

PMID- 9140048
TI  - Evidence for the distinct nature of F2-isoprostane receptors from those of
      thromboxane A2.
AB  - In rat glomeruli and mesangial cells, the thromboxane A2 (TxA2) mimetic, U
      46,619, but not 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), reduced glomerular
      inulin space and increased inositol 1,4,5-trisphosphate production, effects
      abolished by SQ-29,548. In competitive binding studies using 8-iso-[3H]PGF2alpha
      or [3H]SQ-29,548, mesangial cells displayed TxA2 binding sites but not ones for 8
      iso-PGF2alpha. In contrast, rat aortic smooth muscle cells possessed specific
      binding sites for both TxA2 and 8-iso-PGF2alpha and displayed functional
      responses to both agonists, such as time- and dose-dependent activation of
      mitogen-activated protein kinases. In these cells, the mean dissociation constant
      value for the isoprostane receptor was 31.8 +/- 5.7 nM. When human TxA2 receptor
      cDNA was expressed in Xenopus oocytes injected with the Ca2+-specific
      photoprotein, aequorin, 8-iso-PGF2alpha gave much weaker responses than U-46,619.
      These studies provide the first radioligand binding characteristics of the F2
      isoprostane receptor and demonstrate its specific and heterologous cellular
      localization. These studies support the distinct nature and biological
      significance of isoprostane receptors and provide a tool for their further
      molecular characterization.

PMID- 9140050
TI  - Intra- and submembrane particle densities during CO2 stimulation of H+ secretion
      in turtle bladder.
AB  - The apical cell membranes of the H+ secreting, alpha-intercalated cells of turtle
      urinary bladder (TB) are characterized by studs (cytoplasmic domains of V
      adenosinetriphosphatase) on thin-section transmission electron microscopy and by
      intramembrane particles (spherical units, SPUs) occurring as rod-shaped particles
      on freeze-fracture electron microscopy. To examine the relationship between studs
      and SPUs, morphometric studies were carried out on bladders maintained in 5% CO2
      and in the absence of exogenous CO2. The stud density per square micrometer of
      apical membrane was 3,909 +/- 352 (+/-SE) in four TBs (29 alpha-cells) at 5% CO2
      and 3,667 +/- 448 (+/-SE) in the paired halves of the same bladders without CO2
      (25 alpha-cells). Corresponding densities of SPUs counted on apical membranes of
      the same bladders (n = 4) were 3,941 +/- 545 in 5% CO2 and 3,599 +/- 511 without
      CO2. The similarity of the densities of studs and SPUs under both conditions
      indicates that each SPU within the membrane is matched by one stud projecting
      into the cytoplasm. The one-for-one relationship between studs and SPUs was
      preserved over a wide range of transport rates. Addition of CO2 caused only
      inconsistent increments in the densities of studs and SPUs despite substantial
      increases in H+ transport rate. Slight variations in spacing of studs were
      consistent with patterns of distribution of SPUs on fracture surfaces.

PMID- 9140051
TI  - Nitric oxide-induced hyperpolarization stimulates low-conductance Na+ channel of
      rat CCD.
AB  - We used the patch-clamp technique in the split-open cortical collecting duct
      (CCD) to investigate the effect of nitric oxide (NO) on the low-conductance (6
      pS) Na+ channel that can be blocked by 1 microM amiloride. We confirmed that the
      number of Na+ channels increased significantly in CCDs of rats on a low-Na+ diet
      (17). Application of 100 microM N(G)-nitro-L-arginine methyl ester (L-NAME), an
      agent that blocks endogenous NO synthase, reduced NPo [the product of channel
      number (N) and open probability (Po)] to 45% of the control value. The effect of
      L-NAME was specific, since addition of D-NAME, which does not inhibit NO
      synthase, did not change the activity of the Na+ channel. That the effect of L
      NAME results from inhibition of NO synthase is further confirmed by experiments
      in which addition of an exogenous NO donor, either 10 microM S-nitroso-N-acetyl
      penicillamine or sodium nitroprusside (SNP), restored the Na+ channel activity
      when it had been blocked by L-NAME. The action of NO involves a guanosine 3',5'
      cyclic monophosphate (cGMP)-dependent pathway, since 100 microM 8-bromo-cGMP (8
      BrcGMP) mimicked the effect of SNAP on K+ channels. However, 100 microM 8-BrcGMP
      did not alter the activity of Na+ channels in inside-out patches, suggesting an
      indirect action. Because the Na+ channel is activated by hyperpolarization (19)
      and NO stimulates basolateral K+ channels (16), we tested whether
      hyperpolarization mediated the effect of NO. In perforated whole cell recordings,
      addition of L-NAME depolarized the cell membrane from -73 to 51 mV, and
      application of 10 microM SNP repolarized the membrane to -68 mV. Furthermore, the
      L-NAME-induced decrease in NPo was effectively restored by 25 mV
      hyperpolarization of the patch membranes, and addition of 2 mM Ba2+ also
      abolished the effect of L-NAME. We concluded that the stimulatory effect of NO on
      the Na+ channel is an indirect effect mediated by a NO-induced increase of
      basolateral K+ conductance.

PMID- 9140052
TI  - Facilitated transport in vasa recta: theoretical effects on solute exchange in
      the medullary microcirculation.
AB  - A new theoretical model describing the exchange of water and solutes between the
      renal medullary interstitium and the microcirculation was developed to account
      for the presence of water channels and urea transporters, both of which were
      recently identified in the descending vasa recta (DVR) of the renal medulla.
      Small solutes, which are excluded from the water channels, are freely exchanged
      through a parallel pathway shared with water. The transcapillary concentration
      gradients of sodium and urea across the water channels induce water efflux from
      DVR, whereas classic Starling forces across the shared pathway favor volume
      uptake by DVR. Because small solute concentration gradients are large in the
      inner medulla, the model predicts net water removal from DVR, in agreement with
      experimental observations. The descending and ascending vasa recta (AVR) function
      as a countercurrent exchanger, the efficiency of which is inversely related to
      the net amount of solute taken up by the medullary microcirculation. Our results
      indicate that net solute removal from the medulla is governed by convective
      uptake into AVR and thus depends predominantly on the parameters affecting AVR
      transcapillary volume flux. The simulations also suggest that the urea
      transporter significantly enhances the exchange of both sodium and urea and might
      serve to abrogate a reduction in exchanger efficiency imparted by water channels.

PMID- 9140053
TI  - Angiotensin II responses in AT1A receptor-deficient mice: a role for AT1B
      receptors in blood pressure regulation.
AB  - Most of the classic functions of the renin-angiotensin system are mediated by
      type 1 (AT1) angiotensin receptors, of which two subtypes, AT1A and AT1B, have
      been identified. However, distinct functions for these two AT1 receptors have
      been difficult to separate. We examined the pressor effects of angiotensin II in
      Agtr1A -/- mice, which lack AT1A receptors. In enalapril-pretreated Agtr1A -/-
      mice, angiotensin II caused significant and dose-proportional increases in mean
      arterial pressure. This pressor response was not blocked by pretreatment with
      sympatholytic agents but was completely inhibited by the AT1-receptor
      antagonists, losartan and candesartan, suggesting that it is directly mediated by
      AT1B receptors. Chronic treatment of Agtr1A -/- mice with losartan reduced
      systolic blood pressure from 80 +/- 5 to 72 +/- 4 mmHg (P < 0.04), suggesting a
      role for AT1B receptors in chronic blood pressure regulation. These studies
      provide the first demonstration of in vivo pressor effects mediated by AT1B
      receptors and demonstrate that, when AT1A receptors are absent, the AT1B receptor
      contributes to the regulation of resting blood pressure.

PMID- 9140054
TI  - Receptor-mediated endocytosis of immunoglobulin light chains by renal proximal
      tubule cells.
AB  - We examined the binding, endocytosis, and degradation of immunoglobulin light
      chains by primary cultures from rat renal kidneys and immortalized human proximal
      tubule cells. Both the association and dissociation of light chain were rapid and
      plateaued within 30 min at 4 degrees C. Up to 10(-3) M bovine serum albumin did
      not inhibit light chain binding to cells. Internalization studies with 125I
      labeled kappa- and lambda-light chains by cells using the acid wash technique
      showed that up to 80% of total cell-associated binding at equilibrium (30 min) is
      rapidly internalized at 22 degrees C. Comparison of binding and internalization
      of light chains with transferrin, a ligand known to undergo receptor-mediated
      endocytosis, showed that both ligands displayed saturable kinetics. In contrast,
      endocytosis of sucrose, a marker for fluid-phase endocytosis, was unsaturable and
      nearly 200-fold less efficient than light chain internalization. Scatchard
      analysis of binding experiments done at 4 degrees C with trace 125I-labeled
      lambda-light chain in presence of 0 to 3.0 x 10(-3) M cold light chain revealed a
      single class of binding sites with a dissociation constant of 5.0 +/- 0.8 x 10(
      5) and a maximal binding capacity of 1.6 +/- 0.3 x 10(-9) mol/mg cell protein.
      Hypertonic medium, a maneuver which interferes with the formation of the clathrin
      lattice, reduced endocytosis of light chain significantly but did not affect
      endocytosis of sucrose. Chloroquine and bafilomycin A, agents that interfere with
      vesicular acidification, also significantly suppressed light chain endocytosis.
      Using acid precipitation method, we observed that endocytosis of 125I-labeled
      lambda-light chain results in degradation by the rat renal proximal tubule cells.
      Degradation was maximum at 37 degrees C, significantly reduced at 22 degrees C,
      and absent at 4 degrees C. Excess light chain inhibited degradation of
      radiolabel, whereas excess albumin had no effect. These studies document the
      presence of binding sites for light chains on proximal tubule cells that mediate
      endocytosis of light chains by proximal tubule cells. The present data suggest
      that receptor-mediated endocytosis of light chains leads to delivery of this
      ligand to degradative sites through acidified vesicles.

PMID- 9140055
TI  - Ultramicrodetermination of vasopressin-regulated urea transporter protein in
      microdissected renal tubules.
AB  - The vasopressin-regulated urea transporter (VRUT) is a 97-kDa protein (also
      called "UT-1") responsible for facilitated urea transport across the apical
      plasma membrane of inner medullary collecting duct (IMCD) cells. To determine the
      abundance of VRUT protein in collecting duct cells of the rat, we designed a
      sensitive fluorescence-based enzyme-linked immunosorbent assay capable of
      detecting <5 fmol of VRUT protein. In collecting duct segments, measurable VRUT
      was found in microdissected IMCD segments but not in other portions of the
      collecting duct. In the mid-IMCD, the measured level averaged 5.3 fmol/mm tubule
      length, corresponding to approximately 5 million copies of VRUT per cell. Thus
      VRUT is extremely abundant in the IMCD, accounting, in part, for the extremely
      high urea permeability of this segment. Feeding a low-protein diet (8% protein)
      markedly decreased urea clearance but did not alter the quantity of VRUT protein
      in the IMCD. Thus increased urea transport across the collecting duct with
      dietary protein restriction is not a consequence of increased expression of VRUT.
      Based on urea fluxes measured in the IMCD and our measurements of the number of
      copies of VRUT, we estimate a turnover number of > or = 0.3-1 x 10(5) s. In view
      of the large magnitude of this value and previously reported biophysical
      properties of urea transport in collecting ducts, we hypothesize that the VRUT
      may function as a channel rather than a carrier.

PMID- 9140056
TI  - Effect of sympathetic and angiotensin-aldosterone systems on renal salt
      conservation in the rat.
AB  - During dietary salt deprivation, the sympathetic nervous system and the
      angiotensin-aldosterone system are stimulated. Both systems are thought to be
      essential for maximal salt conservation by the kidney. To study their relative
      contributions, we produced negative salt balance in rats by intraperitoneal
      injection of furosemide, followed by a low-salt diet (<0.008% NaCl). In a 1-wk
      metabolic study, the animals were unable to replace the drug-induced salt
      deficit. Six groups of rats were studied. A control group established baseline
      function, a second group of 6-hydroxydopamine (OHDA) rats were treated with OHDA
      to destroy sympathetic efferent nerve terminals, and a third group (losartan)
      were treated with the angiotensin-receptor antagonist losartan. The influence of
      catecholamines and aldosterone released from the adrenal gland was studied in a
      further three groups. Rats were sham-adrenalectomized (sham), subjected to
      bilateral adrenal enucleation (Enuc) to eliminate catecholamine secretion, or
      were bilaterally adrenalectomized (Adx), eliminating both catecholamine and
      corticosteroid release. Dexamethasone was used as glucocorticoid replacement in
      this group. Steady-state urinary salt excretion was not different between control
      and OHDA rats. The losartan group showed significantly increased sodium but not
      chloride excretion. Surprisingly, there were no differences in salt excretion
      among sham, Enuc, and Adx groups. We conclude that, during a state of chronic
      salt depletion, renal mechanism(s) independent of neuronally released or
      systemically circulating catecholamines or of adrenally released aldosterone can
      ensure maximal salt conservation by the kidney. Although our data show that
      losartan increased sodium excretion under these conditions, we suggest that the
      losartan effect can be explained by a reduction of bicarbonate reabsorption,
      obligating simultaneous excretion of the cation.

PMID- 9140057
TI  - Renal resistance to ANF in salt-depleted rats is independent of sympathetic or
      ANG-aldosterone systems.
AB  - Chronic salt depletion was used as a model to study the mechanism of renal
      resistance to the natriuretic effect of atrial natriuretic factor (ANF). Rats
      were pretreated with furosemide and placed on a low-salt diet (<0.008% NaCl) for
      1 wk before a clearance experiment. Compared with animals on a normal salt diet
      (0.4% NaCl), the natriuretic reponse to ANF administration was reduced by one
      order of magnitude and was quantitatively trivial. To assess the influence of the
      sympathoadrenergic system, different groups of rats were either subjected to
      acute unilateral renal denervation, to chronic adrenal enucleation to reduce
      circulating catecholamines, or to pretreatment with 6-hydroxydopamine (OHDA) to
      destroy sympathetic postganglionic nerve endings. None of these treatments was
      able to fully or even partially restore ANF natriuresis. To determine whether an
      effect of angiotensin on the kidney prevented the response, the specific receptor
      antagonist losartan (DuP-753) was administered during the week prior to the
      experiment. This treatment also did not influence ANF resistance. Similarly,
      bilateral adrenalectomy 2 wk before the experiment did not affect the renal ANF
      resistance in salt-depleted rats. The depressed excretory response could not be
      explained on the basis of reduced renal perfusion pressure or glomerular
      filtration rate. We conclude that undetermined compensatory mechanism(s) ensures
      renal salt conservation in this model in the face of even supraphysiological
      levels of ANF.

PMID- 9140058
TI  - Expression of carbonic anhydrase IV mRNA in rabbit kidney: stimulation by
      metabolic acidosis.
AB  - The renal carbonic anhydrases, CA II (cytosolic) and CA IV (membrane bound), are
      believed to facilitate renal acid secretion. We have recently shown that renal
      cortical sodium dodecyl sulfate (SDS)-resistant hydratase (presumably CA IV)
      activity was stimulated 241% during chronic metabolic acidosis (CMA). In the
      present study, we examined the expression and regulation of CA IV mRNA in kidneys
      from control and acidotic rabbits. To obtain a CA IV probe, we reverse
      transcribed rabbit kidney total RNA and amplified a approximately 780-base pair
      (bp) DNA product using primers derived from the human CA IV sequence. Using this
      product, we screened one-half of a kidney cortex cDNA library and sequenced a
      1,194-bp cDNA, which contained the entire open-reading frame of rabbit CA IV. The
      cDNA was 78% identical to human and 71% to rat CA IV. The deduced amino acid
      sequence projected an active zinc binding site and two glycosylation sites.
      Northern analysis yielded a single transcript of approximately 1,600 bp in size
      expressed more abundantly in cortex and inner medulla than in outer medulla. CA
      IV mRNA was also expressed abundantly in lung but not in liver or spleen. The
      high abundance of CA IV mRNA in inner medulla was localized by in situ
      hybridization to medullary collecting duct cells. Rabbits exposed to CMA showed
      significant upregulation of CA IV mRNA expression in kidney cortex and outer
      medulla. Despite a numerical increase, excessive variability precluded
      statistical significance in the inner medulla. Thus CA IV mRNA was expressed
      abundantly in kidney and stimulated by CMA, similar to what has been previously
      observed for SDS-resistant hydratase (presumed CA IV) activity. It is likely that
      the regulation of CA IV mRNA and activity is relevant to the kidney's adaptation
      to CMA.

PMID- 9140059
TI  - MutT-related error avoidance mechanism for DNA synthesis.
AB  - Mutator mutants that show an increased frequency of spontaneous mutation have led
      to the elucidation of the multiple pathways of spontaneous mutagenesis. 8-Oxo
      dGTP (8-oxo-7,8-dihydrodeoxyguanosine triphosphate) is formed in the nucleotide
      pool of a cell during normal cellular metabolism, and when it is incorporated
      into DNA causes mutation. MutT protein of Escherichia coli and related mammalian
      enzymes specifically degrade 8-oxo-dGTP to 8-oxo-dGMP, thereby preventing
      occurrence of transversion mutation. The gene encoding the human enzyme,
      designated MTH1 (for mutT homologue 1), maps to chromosome 7p22. These proteins
      may be responsible for genomic stability.

PMID- 9140060
TI  - Vertebrate non-receptor protein-tyrosine kinase families.
AB  - Many non-receptor protein-tyrosine kinases (PTKs) function as subunits of
      receptors, either receptors with or without intrinsic PTK catalytic activity of
      their own. There are currently at least 33 known vertebrate genes that encode non
      receptor PTKs. These can be divided into nine families: Abl, Fes/Fer, Syk/Zap70,
      Jak, Tec, Fak, Ack, Src, and Csk. Four additional non-receptor PTKs (Rlk/Txk,
      Srm, Rak/Frk, and Brk/Sik) do not appear to belong to any of the defined
      families. Here we review current knowledge of the general roles of non-receptor
      PTKs, as well as the characteristic features and functions of each family and its
      family members.

PMID- 9140061
TI  - Differential thermoregulation of two highly homologous cold-shock genes, cspA and
      cspB, of Escherichia coli.
AB  - BACKGROUND: The major cold-shock protein in Escherichia coli is CspA, a 7.4 kDa
      protein. A CspA family has been found which consists of four additional proteins,
      CspB, CspC, CspD and CspE. The expression of cspB, unlike the other homologues,
      is cold-shock inducible like cspA. RESULTS: We examined the cold-shock induction
      of CspA and CspB at various temperatures. The cspA induction is observed by
      temperature shift from 37 to 30 degrees C and high levels of CspA production are
      observed between 24 and 10 degrees C. In contrast, CspB production occurs only by
      temperature shift to below 20 C, with maximum induction at 15 degrees C. Both
      cspA and cspB expressions were found to be induced at the level of transcription
      as determined by primer extension. CONCLUSIONS: These results show that cspA and
      cspB expressions are differentially regulated at low temperature indicating that
      E. coli contains at least two different biothermostats or thermoregulators that
      are likely to play important roles in cellular adaptation to low temperature. The
      cspB promoter shows sequence similarity to the cspA promoter. Furthermore, both
      cspA and cspB mRNAs have unusually long 5' untranslated regions (159 and 161
      bases, respectively), both of which are able to form similar extensive secondary
      structures. These features are considered to contribute to the nature of the
      thermostats for cspA and cspB.

PMID- 9140062
TI  - Histone-like protein HU as a specific transcriptional regulator: co-factor role
      in repression of gal transcription by GAL repressor.
AB  - BACKGROUND: Transcription initiation from the two overlapping promoters of the
      gal operon in Escherichia coli is negatively regulated by binding of Gal
      repressor (GalR) to bipartite operators, which encompass the promoters.
      Coordinated repression of the two promoters requires GalR binding to both
      operators. In a purified system, GalR, nevertheless, fails to show the
      coordinated repression, predicting the participation of an additional factor(s)
      in the regulation in vivo. RESULTS: We have purified a protein that restored the
      expected GalR-mediated repression for the in vitro system and have identified
      this factor to be the bacterial histone-like protein HU. In vitro transcription
      assays in the presence of GalR and HU show that, just as in vivo, the coordinated
      repression of the two gal promoters requires GalR binding to both operators and
      is sensitive to the inducer, D-galactose. The GalR and HU dependent repression
      also requires supercoiled DNA template and prevents open complex formation.
      CONCLUSION: We propose that HU, acting as a co-factor, brings about the GalR
      mediated repression by forming a distinct nucleoprotein complex of higher order
      structure. Although how HU participates in the assembly process is unknown, there
      may be a cooperative effect in the formation of the repression complex.

PMID- 9140063
TI  - Dissociation kinetics of RepA dimers: implications for mechanisms of activation
      of DNA binding by chaperones.
AB  - BACKGROUND: The replication initiator of plasmid P1, RepA, binds DNA as monomer.
      The binding is stimulated by the chaperones DnaJ, DnaK and GrpE of Escherichia
      coli. Two models of chaperone action have been proposed. (i) Chaperones
      dissociate RepA dimers, which are inactive in DNA binding, into active monomers.
      (ii) The dissociation occurs spontaneously but the monomeric products require the
      chaperones for refolding into the active form. The latter model was based on the
      observation that RepA diluted 1000-fold below the K(D) for dimer dissociation,
      still required the chaperones for DNA binding. RESULTS: We have confirmed that
      under the condition of DNA binding experiments, the RepA dimers dissociate
      reversibly into monomers with a K(D) value of 1.1 +/- 0.1 microM. In the vicinity
      of this concentration, the sedimentation coefficient of RepA was concentration
      dependent, allowing estimation of s(20,w) coefficients for the RepA monomer (2.95
      S) and dimer (4.01 S). Dynamic light scattering experiments indicated an increase
      of the monomer fraction within 5 min of RepA dilution. Circular dichroism (CD)
      measurements were consistent with these results. CONCLUSION: RepA monomerization
      is efficient without the mediation of chaperones. They are required to activate
      RepA most likely because they are needed to re-fold RepA monomers.

PMID- 9140064
TI  - Roles of cysteine residues of DsbB in its activity to reoxidize DsbA, the protein
      disulphide bond catalyst of Escherichia coli.
AB  - BACKGROUND: DsbA, a periplasmic protein, catalyses the disulphide bond formation
      of other cell surface proteins in E. coli. Reoxidation of DsbA for catalytic turn
      over is assured by DsbB, a membrane protein with four essential cysteine residues
      facing the periplasm. We and others previously reported that the reactive Cys30
      residue of DsbA forms a mixed disulphide with DsbB in the absence of its partner
      Cys33 residue. RESULTS: Under the medium condition in which the DsbA mutant
      lacking Cys33 forms a mixed disulphide only with DsbB, we examined cysteine
      mutants of epitope-tagged DsbB for their ability to form the complex. It was
      shown that Cys104 of DsbB is absolutely required while other three cysteines are
      also required for maximum interaction. Examination of the redox states of
      cysteines in wild-type and mutant DsbB suggested that Cys104 and Cys130 form a
      disulphide bond which will be transferred to DsbA. In agreement with this notion,
      DsbB mutants lacking one of the N-terminally located cysteines retain weak DsbB
      activity in vivo. The primary role of the N-terminally located thioredoxin-like
      motif of DsbB is probably to reoxidize Cys104 and Cys130. CONCLUSIONS: We propose
      the following reaction cycle. DsbB is initially oxidized (State A in Summary
      Figure). Disulphide interaction between Cys30 of DsbA and Cys104 of DsbB should
      then trigger the recycling reaction of DsbA (State B), allowing over all electron
      transfer from newly secreted protein via DsbA (Cys30/Cys33) to DsbB in which
      intrachain electron flow from Cys104/Cys130 (State C) to Cys41/Cys44 (State D)
      may occur.

PMID- 9140065
TI  - Inhibition of ligand induced promoter occupancy in vivo by a dominant negative
      RXR.
AB  - BACKGROUND: Retinoid X receptors (RXRs) heterodimerize with other nuclear hormone
      receptors and control ligand mediated transcription. To address how RXRs function
      as heterodimers, we investigated activities of truncated RXR alpha and RXR beta
      that lack approximately 20 conserved C-terminal amino acids. RESULTS: The
      truncated RXRs formed heterodimers and bound to respective DNA elements in vitro.
      By transient reporter assays we found that these RXRs act as dominant negative
      receptors and inhibit ligand dependent transcription by the retinoic acid
      receptor (RAR) and vitamin D receptor. P19 embryonal carcinoma cells stably
      expressing the truncated RXR beta (termed delta C2) were deficient in activating
      the endogenous RAR beta gene and an RA responsive reporter. To study the dominant
      negative activity of delta C2 further, genomic footprinting analysis was
      performed for the RAR beta2 promoter. In control P19 clones, the RA responsive
      element (RARE) and other elements in the promoter were protected after RA
      treatment. However, in delta C2 clones RA-induced protection was markedly
      inhibited at all elements. CONCLUSIONS: These results indicate that the C
      terminal region of RXR is required for full RARE occupancy in vivo, a RA
      dependent process that leads to the recruitment of other factors to the promoter
      and the subsequent transcriptional activation. Thus, RXRs play an integral role
      in ligand dependent transcription.

PMID- 9140066
TI  - Mesodermal- vs. neuronal-specific expression of MafK is elicited by different
      promoters.
AB  - BACKGROUND: Small members of the Maf family of transcriptional regulatory
      proteins share similar basic-leucine zipper domains but have no intrinsic ability
      to activate transcription. One member of the family (MafK) has been shown to
      mediate both negative and positive regulation: in addition to forming a homodimer
      which represses transcription, MafK can also form a heterodimer with p45 (the
      large subunit of erythroid transcription factor NF-E2) to activate transcription.
      RESULTS: We examined the expression of mafK during murine development. mafK mRNA
      was first detected in 7.5 days post coitus (dpc) embryonic mesoderm and persisted
      in mesodermal derivatives (mesenchymal and haematopoietic cells) thereafter.
      However, around 13 dpc mafK was also strongly induced in neuronal cells and it is
      broadly expressed in neurones in postnatal mouse. The neuronal expression of mafK
      is directed by a distinct promoter located 6 kbp 3' to the mesoderm-specific
      promoter. mafK in neurones associates with a different partner molecule from p45.
      In transgenic mice, a regulatory domain in the immediate vicinity of the
      mesodermal promoter was found to direct mesenchymal, but not haematopoietic,
      expression of mafK. CONCLUSION: The cell type- and developmental stage-specific
      expression of MafK suggests that, in addition to its demonstrated role in
      erythroid transcriptional regulation, MafK also plays an important regulatory
      role in other mesodermally and neuroectodermally derived tissues during mouse
      embryonic development.

PMID- 9140067
TI  - Identification of putative downstream genes of Oct-3, a pluripotent cell-specific
      transcription factor.
AB  - BACKGROUND: Oct-3, a pluripotent cell-specific POU transcription factor, appears
      to be a key regulator in pluripotential early embryonic cells and germ cells. In
      order to study how pluripotency is maintained, it is essential to know what genes
      are regulated by Oct-3. RESULTS: By employing a subtraction method, we identified
      several pluripotent cell-specific genes. Based upon expression patterns in
      various cell lines lacking or possessing Oct-3 function, about half of the genes
      were placed downstream of Oct-3. These downstream genes included a previously
      known gene (Glut-3: a gene for a glucose transporter) and novel genes (226, 383
      and 880). Their expression patterns paralleled that of Oct-3: all of these genes
      were highly expressed in pluripotent cells such as EC/ES cells, but switched off
      upon differentiation. More importantly, their expression was rescued in
      'revertant' cells that ectopically acquired the Oct-3 transactivating function.
      Furthermore, the expression profiles of Glut-3, 226 and 383 during mouse
      development also overlapped that of Oct-3. The Glut-3 gene possessed multiple Oct
      3 binding sites in its transcriptional regulatory regions, suggesting that at
      least one of the downstream genes was a direct target of Oct-3. CONCLUSIONS: A
      large proportion of pluripotent cell-specific genes appear to be downstream
      targets of Oct-3.

PMID- 9140068
TI  - Dopamine D2 receptor plays a critical role in cell proliferation and
      proopiomelanocortin expression in the pituitary.
AB  - BACKGROUND: It has been suggested that the dopaminergic system is involved in the
      inhibitory control of secretion of pituitary hormones and in the regulation of
      motor function in the striatum. To elucidate the specific role of the dopamine D2
      receptor (D2R) in the pituitary and brain, we generated D2R deficient (D2R
      mutant) mice using the gene targeting method. RESULTS: Electrophysiological
      studies as well as ligand binding assays show no functional D2R in mutant mice.
      The D2R mutant mice display a hypoactivity and a slow, creeping movement. The
      expression of enkephalin mRNA in the striatum is increased in the mutant mice,
      but not that of dynorphin and substance P. D2R mutant mice have significantly
      darker coat colour than their wild-type littermates and show an elevation of
      plasma alpha-melanocyte stimulating hormone (alpha-MSH) levels. We found
      corresponding hyperplastic changes of intermediate lobe of the pituitary and the
      increased expression of pro opiomelanocortin (POMC) in the pituitary in D2R
      mutant mice. CONCLUSIONS: D2R plays a critical role in the inhibitory regulation
      of endocrine cell proliferation and the transcription of POMC mRNA, and
      consequently in the regulation of alpha-MSH in plasma. D2R might be involved in
      the regulation of enkephalin expression in the striatum, and hence might affect
      the movement and the behaviour.

PMID- 9140069
TI  - Phosphorylation of insulin-like growth factor binding proteins.
AB  - Insulin-like growth factor (IGF) binding proteins (IGFBPs) play a key role in
      regulating the availability of IGFs in the circulation and the extracellular
      environment. Three of these proteins-IGFBP-1, IGFBP-3 and IGFBP-5-are known to be
      serine-phosphorylated in their central domains, and the others have possible
      target sites for serine/threonine kinases. Whereas nonphosphorylated IGFBP-1 may
      potentiate IGF action in certain cells, phosphorylation increases its affinity
      for IGFs, and converts the protein to an inhibitory form. The highly
      phosphorylated protein predominates in the circulation, where it may acutely
      regulate IGF bioavailability. IGFBP-3 is also secreted as a phosphoprotein, and
      can be phosphorylated in vitro by protein kinases A and C, and casein kinase II.
      De-phosphorylation has no effect on IGF-binding, but may increase its ability to
      bind to the acid-labile subunit and to associate with cell surfaces. Although no
      specific functions have yet been ascribed to phosphorylated forms of the other
      IGFBPs, current evidence supports the proposal that IGFBP phosphorylation plays
      an important role in the regulation of IGFBP function.

PMID- 9140070
TI  - Quo vadis: extrasomatic targeting of neuronal mRNAs in mammals.

PMID- 9140071
TI  - Epitope analysis of the thyrotropin receptor, 1997.

PMID- 9140072
TI  - Development of a dose-response bioassay for stanniocalcin in fish.
AB  - Stanniocalcin (STC) is a polypeptide hormone that was first discovered in fish
      and recently identified in mammals. In fish, STC is released into the bloodstream
      in classical endocrine fashion and has well established regulatory effects on
      calcium and phosphate homeostasis. However, there are no suitable dose-response
      bioassays for STC and consequently no methods for assigning units of potency to
      preparations of the hormone. All the available in vitro bioassays are too complex
      from a technical standpoint to readily accommodate the large number of samples
      required in dose-response bioassays. Most in vivo bioassays are hampered by the
      fact that fish have natural rhythms governing plasma STC levels which tend to
      make them variably sensitive to the injected hormone. In this report we have
      developed a new in vivo bioassay for STC using rainbow trout. The key feature of
      the bioassay involves suppressing plasma STC levels to the extent that fish are
      always receptive to injected hormone. This has been accomplished by phosphate
      loading the animals, which lowers their plasma calcium levels, removes the
      stimulus for STC secretion and brings about a reduction in resting plasma hormone
      levels. The net effect is an animal that is always responsive to injected STC.
      With this bioassay we have been able to obtain sensitive and reproducible, dose
      related effects of salmon STC on gill calcium transport.

PMID- 9140073
TI  - Crosstalk during Ca2+-, cAMP-, and glucocorticoid-induced gene expression in
      lymphocytes.
AB  - In the WEHI7.2 thymoma cell line, cAMP, glucocorticoids, or increases in
      cytosolic Ca2+ concentration lead to cell death by apoptosis. In the present
      study, we examined the effects of these compounds on cAMP response element (CRE)
      mediated gene expression. Thapsigargin and A23187 were employed to increase
      cytosolic Ca2+ levels and induce apoptosis. Both compounds enhanced transcription
      from a CRE preceding apoptotic death. Moreover, the transcriptional response to
      the combination of forskolin and either thapsigargin or A23187 was synergistic
      mirroring the effect on cell death. Importantly, dexamethasone treatment, which
      causes an efflux of Ca2+ from the ER, induced transcription from a CRE alone or
      in synergy with forskolin. The increase in CRE-controlled gene expression
      correlated with a decrease in cell viability. Following treatment with forskolin,
      thapsigargin, or dexamethasone, the CRE binding protein (CREB) was phosphorylated
      at levels correlating with the level of induced gene expression. These data
      suggest that transcriptional crosstalk between independent signaling pathways
      occurs in lymphocytes, and CREB may play a central role in the mediation of CRE
      dependent transcription by these diverse set of apoptotic agents.

PMID- 9140074
TI  - Cleavage-secretion of angiotensin I-converting enzyme in yeast.
AB  - Angiotensin I-converting enzyme (ACE) is a type I transmembrane protein composed
      of two domains (N and C domains) which undergoes a post-translational proteolytic
      cleavage in mammalian cells to release the soluble ectodomain. The protease
      involved in ACE cleavage-secretion (ACE-secretase) is not well characterised and
      eludes isolation: the presence of a yeast homologue, thus more amenable to
      genetic manipulation, would facilitate its identification. We have expressed a
      secreted form of the ACE C domain, lacking the C-terminal membrane anchor (C
      domain(deltaCOOH)), and the membrane-anchored C domain (C domain) in the yeast
      Pichia pastoris by fusion to prepro-alpha-factor. Immunofluorescent labelling
      localises the ACE C domain to the periphery of yeast cells but not C
      domain(deltaCOOH), however, expression of both C domain and C domain(deltaCOOH)
      produced soluble enzymes in the culture medium. Immunocharacterisation of the two
      soluble forms of the C domain indicates a proteolytic cleavage of the membrane
      bound C domain to produce the soluble counterpart. Thus ACE undergoes a
      proteolytic cleavage in yeast.

PMID- 9140076
TI  - Insulin-like growth factors control the regulation of oestrogen and progesterone
      receptor expression by oestrogens.
AB  - Ligands for the type I insulin-like growth factor (IGF) receptor interact with
      oestrogens to control the proliferation of oestrogen responsive breast cancer
      cells. The aim of this study was to determine the involvement of ligands for the
      type I IGF receptor in the regulation of oestrogen receptor (OR) expression by
      oestrogens and antioestrogens in these cells. Oestrogen decreased OR mRNA levels
      in MCF-7 cells whereas it increased them in T47D, EFM-19 and ZR-75 cells. In MCF
      7 cells, IGF-I and insulin lowered further OR expression in the presence of
      oestrogen. In the presence of IGF-I or insulin, the induction of progesterone
      receptor mRNA by oestradiol was considerably attenuated in MCF-7 cells, showing
      that the enhanced down-regulation of OR mRNA levels influenced the expression of
      oestrogen-regulated genes. The oestrogen agonist activity of the antioestrogens
      tamoxifen and ICI 182 780 for the down-regulation of OR expression in MCF-7 cells
      was modulated by type I IGF receptor ligands. Overall these experiments show that
      OR expression is differentially regulated by oestrogen in individual oestrogen
      responsive breast cancer cell lines. Ligands for the type I IGF receptor can
      modulate regulation of OR expression by oestrogens and antioestrogens principally
      in cells in which oestrogens down-regulate OR expression.

PMID- 9140075
TI  - Recombinant rat luteinizing hormone; production by Chinese hamster ovary cells,
      purification and functional characterization.
AB  - Rat recombinant (rec) luteinizing hormone (LH) was produced in Chinese hamster
      ovary (CHO) cells, to enable studies on LH physiology in this species with
      homologous hormone. The synthesized hormone was purified, and characterized
      physico-chemically and biologically in comparison with highly purified
      preparations of rat pituitary (pit) LH (NIDDK-rLH-I-7 and I-9) and to highly
      purified urinary (NIH, CR-121) and rec forms of human chorionic gonadotropin
      (hCG). The 33 kD molecular mass of rat recLH, as determined by SDS-polyacrylamide
      gel electrophoresis (SDS-PAGE) and Western blot, was comparable with the 32 kD
      size of pitLH. In chromatofocusing, the isoforms of rat recLH distributed in the
      pI range 6.5-7.8, similar to rat pitLH. In receptor binding assays using rat
      testicular membranes, and physiologic salt concentration, rat recLH displayed a 5
      10-fold higher affinity than rat pitLH, but about 100-fold lower affinity than
      hCG. In contrast, in low salt concentrations the affinities of rat recLH and
      rechCG to rat LH receptor were rather similar. The differences in potency in the
      mouse Leydig cell in vitro bioassay were in agreement with the receptor binding
      data at physiologic salt concentration. Neither rat recLH nor pitLH stimulated
      cAMP production or bound specifically to HEK 293 cells expressing the rec human
      LH receptor. When injected subcutaneously on four consecutive days to male rats
      (8.4-33.7 microg/rat/day) rat recLH did not induce seminal vesicle growth in
      comparison with a significant effect of human menopausal gonadotropin (hMG; 12.5
      50 IU/rat/day). In contrast, ovulation was induced in 5/6 and 6/6 female rats
      following single injections of 3.75 and 7.5 microg of rat recLH, respectively,
      after pretreatment with 10 microg/kg of a GnRH-antagonist (Org 30850). In
      conclusion, rat recLH displays clearly lower in vivo and in vitro bioactivity
      than hCG. Nevertheless, it binds effectively to the rat LH receptor (with
      affinity dependent on salt concentration) and is bioactive in the mouse Leydig
      cell bioassay. This newly synthesized recombinant hormone provides a useful tool
      for further studies on the physiology of LH action in the rat, the most common
      animal model in reproduction research.

PMID- 9140077
TI  - Thyroid hormone activates transcription from the promoter regions of some human
      nuclear-encoded genes of the oxidative phosphorylation system.
AB  - Thyroid hormone (T3) modulates the mRNA levels for cytochrome c and the adenine
      nucleotide translocator-2 (ANT2) in adult rat liver. Here we show that T3
      activates expression of a reporter gene driven from the human cytochrome c1 and
      ANT2 promoters transfected into human choriocarcinoma JEG3 cells. By contrast,
      the human F1-ATPase beta-subunit promoter responded marginally, thus providing a
      pattern of differential expression similar to that earlier observed in rats in
      vivo. T3-activation is dependent on co-expression of the thyroid hormone receptor
      (TR alpha1). Co-expression of both the TR and RXR receptors had no additional
      effect. Transient transfection of deletion constructs showed that T3 activation
      is retained by the proximal regions of the cytochrome c1 and ANT2 promoters, and,
      in the case of cytochrome c1, is lost upon removal of a fragment containing the
      transcription initiator ((nucleotides) (nt) + 1 to + 100). The promoter regions
      supporting T3-activation of the reporter genes appear to lack strong DNA binding
      sites for TR and retinoid X receptor (RXR).

PMID- 9140078
TI  - Changes in responsiveness of freshly isolated longitudinal muscle cells from rat
      uterus towards oxytocin during gestation: contractility and calcium signaling.
AB  - Changes in responsiveness of freshly isolated longitudinal muscle cells from rat
      uterus to oxytocin during gestation were investigated through measuring
      contractility as well as intracellular free calcium concentration. We have
      demonstrated the pregnant stage-dependent contraction of freshly isolated
      myometrial cells in response to an extracellular hormone, oxytocin, in Ca2+
      containing medium. The oxytocin effect appeared to be through oxytocin receptor
      since the effect could be blocked by a specific oxytocin antagonist. The
      magnitude of the contraction of the isolated cells in response to extracellular
      oxytocin was in the order of 21 day >> 18 day > 15 day pregnant rat longitudinal
      muscle cells. In a concentration dependent manner, oxytocin elicited a rapid
      increase in [Ca2+]i of longitudinal muscle cells isolated from different stages
      of the pregnant rat uterus, especially at the term of pregnancy. The time (4-5 s)
      required to reach a maximum increase in [Ca2+]i of the isolated longitudinal
      muscle cells in response to oxytocin was the shortest among all previously
      reported studies. The results also indicated that the freshly prepared
      longitudinal muscle cells maintained their functional calcium signaling system.
      The order of the responsiveness of the isolated longitudinal muscle cells to
      oxytocin was 21 day >> 18 day > 15 day pregnant rats in terms of rate, affinity
      and magnitude. Oxytocin appears to transmit its signal mainly through stimulating
      a voltage-dependent and/or receptor operated nonselective calcium channel.
      However, the possibility that a part of the oxytocin action occurs through
      stimulating the release of calcium from intracellular store sites of longitudinal
      muscle still remains.

PMID- 9140079
TI  - The function of retinoid X receptors on negative thyroid hormone response
      elements.
AB  - Retinoid X receptors (RXRs) form heterodimers with thyroid hormone receptors
      (TRs). RXRs increase DNA binding affinity of TRs and T3-mediated transactivation
      on positive T3 response elements (TREs). However, the role of RXRs on negative
      TREs, and the relation of RXRs to the dominant negative effect of mutant TRs, are
      not defined. To clarify the function of RXRs on negative TREs, we performed
      transient cotransfection studies using the rat glycoprotein hormone alpha
      promoter fused to luciferase gene (alphaLuc), and human TRH promoter fused to
      luciferase gene (TRH-Luc) as reporters. We found that the JEG-3 cell-alphaLuc
      system was very sensitive to TR regulation. Using TRbeta1 wild-type (WT)
      expression vector, 6.2 ng/well (170 ng/10 cm dish), and 0.2 ng/well (11 ng/10 cm
      dish) caused maximal, and half maximal, inhibition of Luc activities in the
      presence of 1 nM T3. A T3 dose dependent inhibition study was also performed.
      From these studies, we determined that the appropriate conditions in which to
      study alphaLuc transactivation, in a linear portion of the dose response curve,
      was using 0.8 ng/well TRbeta1 expression vector and 0.1 nM T3. Under these
      conditions, TRbeta1 mutant R316H (GH), but not G345R (Mf), showed a weak dominant
      negative effect at a 1:1 ratio in the presence of 0.1 nM T3 although neither
      mutant had detectable T3 binding affinity. Moreover this dominant negative effect
      of R316H on the alphaLuc reporter was enhanced in the presence of RXRgamma.
      Mutant G345R showed a stronger dominant negative effect than did R316H when using
      a double palindromic TRE fused to herpes simplex thymidine kinase-Luc reporter as
      a positive TRE. These results conform to the clinical features of R316H which is
      associated with apparent pituitary resistance of thyroid hormone (PRTH). Mutant
      R316H also showed a weak dominant negative effect with TRH-Luc at a 1:1 ratio in
      the absence or presence of RXRgamma. However RXRgamma did not enhance the
      dominant negative effect as it did using alphaLuc reporter gene. Electrophoretic
      gel mobility shift assay (EMSA) showed that RXR alpha augmented the DNA binding
      affinity of wild type and R316H TRs as heterodimers on the previously reported
      negative TREs of glycoprotein hormone alpha promoter, suggesting that RXR does
      not produce its response by removing TRs from these TREs. RXR alpha augmented DNA
      binding affinity of TRbeta1WT, and R316H showed a weaker heterodimer band than
      did the wild type in EMSA. Using the TRH-Luc reporter, basal activity was
      increased by wild type TRbeta1. However a TRbeta1 DNA binding domain mutant,
      (C127S) which can not bind to DNA, did not increase the basal activity. This
      indicates that DNA binding of the TR is required for increasing basal activity of
      TRH promoter. These results indicate that (1) RXR-TR heterodimers play a role in
      basal transactivation and T3 suppression of negatively regulated genes, and (2)
      RXRs increase the dominant negative effect of some mutant TRs on specific
      negative TREs. (3) This effect occurs without removing TRs from the TRE. (4) The
      differential dominant negative effect of mutant R316H (negative TRE > positive
      TRE) may explain, at least in part, the presentation of R316H as PRTH. (5)
      Augmentation of basal activity by wild type TRs on a negative TRE requires DNA
      binding.

PMID- 9140080
TI  - Glucose transport correlates with GLUT2 abundance in rat liver during altered
      thyroid status.
AB  - Glucose transport activity ([3H]D-glucose uptake) in liver sinusoidal membrane
      vesicles (SMVs) from hyperthyroid rats was significantly higher than that from
      euthyroid controls (2.1-times increase in V(max) with K(m) unchanged at
      approximately 18 mM), associated with increased GLUT2 expression. In contrast,
      glucose transport V(max) into SMVs from hypothyroid rats was reduced to 0.75
      times that of euthyroid controls, associated with a reduced GLUT2 abundance.
      GLUT1 expression in SMVs was unaffected by changes in thyroid status. GLUT2, but
      not GLUT1 abundance on the blood-facing membrane of liver cells is sensitive to
      changes in thyroid status and these changes in transporter expression directly
      correlate (r = 0.96) with altered glucose transport activity.

PMID- 9140081
TI  - Variation in placental type 2 11beta-hydroxysteroid dehydrogenase activity is not
      related to birth weight or placental weight.
AB  - It has been suggested that the association between the development of
      hypertension and a combination of low birth weight and high placental weight can
      be explained by variations in expression of NAD+-dependent 11beta-hydroxysteroid
      dehydrogenase (11-HSD2 or 11-HSD K) in the placenta. Enzymatic activity and mRNA
      levels of 11-HSD2 were measured in 111 human placentas taken from normal births.
      There were no correlations between either 11-HSD2 activity or mRNA levels and
      either fetal or placental weight. These studies suggest that variations in
      placental 11-HSD activity do not influence fetal or placental weight in humans.

PMID- 9140082
TI  - Calcitonin mRNA is produced in liver by two different splicing pathways.
AB  - Calcitonin, the hypocalcemic hypophosphatemic hormone is produced in the thyroid
      by the C-cells. We recently detected the presence of calcitonin and its messenger
      in hepatic tissue in vivo and in vitro. The calcitonin precursor is composed of
      the N-terminal peptide, calcitonin and a carboxyterminal peptide. We previously
      reported that in normal human thyroid and in medullary thyroid carcinoma a second
      calcitonin messenger is expressed in low quantities. This mRNA differs in its 3'
      region from the first one. It also codes for the N-terminal peptide, calcitonin
      and a carboxyterminal peptide which differs by the last eight amino acids from
      the first. We report here that both calcitonin mRNAs are expressed in normal or
      tumoral liver. Direct estimation, by a specific immunoassay, of the levels of
      carboxyterminal peptide II, the specific peptide coded for by calcitonin mRNA II,
      confirmed that this peptide is synthesized in human liver.

PMID- 9140083
TI  - Regulation of interleukin (IL)-1alpha, IL-1beta, and IL-6 expression by growth
      hormone and prolactin in bovine thymic stromal cells.
AB  - Growth hormone (GH) and prolactin (PRL) have been implicated in T-cell
      development, but relatively little is known about the mechanism(s) of their
      actions on the multiple cell types in this complex tissue. Here, we investigated
      the effects of GH and PRL on the expression of interleukin (IL)-1alpha, IL-1beta
      and IL-6 in thymic stromal cells (TSC). These cytokine mRNAs were increased by
      GH, PRL and placental lactogen (PL) in primary cultures prepared from mid
      gestational fetuses in a dose-dependent manner. IL-1 receptor antagonist (IL-1ra)
      abolished the hormone-induced IL-6 expression, suggesting that the induction of
      IL-6 was secondary to IL-1 activity. To examine the effects of these hormones on
      an individual cell type and develop a system in which signalling mechanisms can
      be studied, we generated immortalized cell lines using a strategy of conditional
      transformation. In the cell line, TSC-936, which displayed vimentin-positive
      staining and morphological characteristics of mesenchymal cells, both GH and PRL
      increased levels of steady-state mRNAs for IL-1alpha and IL-1beta. Nuclear run-on
      analysis revealed that the transcription rate of the IL-1beta gene was
      significantly increased by GH and PRL at 30 and 60 min, respectively, but that
      for IL-1alpha was not significantly changed, suggesting the possibility of an
      alternative mechanism mediating this response. These data suggest that modulation
      of cytokine gene expression is one mechanism by which GH and PRL facilitate
      thymic development and T-cell maturation.

PMID- 9140084
TI  - Cleavage site mutants of the subtype B insulin receptor are uncleaved and fully
      functional.
AB  - The insulin receptor (IR) is a membrane-bound glycoprotein composed of alpha and
      beta subunits derived from a common precursor. This processing is observed for
      both subtypes A and B of the IR and its physiological importance is poorly
      understood. In order to investigate the functional consequences of the absence of
      IR precursor cleavage, using site-directed mutagenesis of the hIRB cDNA, we have
      produced two mutants replacing the sequence Arg-Lys-Arg-Arg by either His-Lys-His
      Arg or Arg-Lys-Arg-Ser. These two mutants, stably expressed in CHO, were
      structurally and functionally characterized in comparison to the wild-type human
      IR. These mutations result in the production of uncleaved receptors which are
      expressed normally at the cell surface. These receptors bind insulin with a
      normal affinity and activate the tyrosine-kinase resulting in normal
      phosphorylation of the receptors. These uncleaved receptors can mediate both the
      metabolic and mitogenic effects of insulin. These results provide evidence for a
      fully functional uncleaved insulin receptor of the B subtype (exon 11 + ) in
      contrast to the uncleaved A subtype (exon 11 -) described in the literature,
      which shows a reduced affinity for insulin and cannot therefore correctly
      transduce the insulin signal.

PMID- 9140085
TI  - Involvement of a 3beta-hydroxysteroid dehydrogenase activity in ecdysteroid
      biosynthesis.
AB  - Ecdysteroid biosynthesis was analyzed in vitro using dissociated Y-organ cells
      from the shore crab Carcinus maenas. 3-Dehydroecdysone (3DE) was detected as a
      minor secretory product, in addition to the formerly identified end-products 25
      deoxyecdysone and ecdysone (E). In conversion studies, 3DE was formed from
      tritiated 5beta-ketodiol (2,22,25-trideoxyecdysone), 2,22-deoxyecdysone and 2
      deoxyecdysone but not from E. Further experiments were performed in order to
      understand the interconversions between 3-oxo and 3beta-OH compounds in the crab
      Y-organ. The enzyme involved in 3beta-dehydrogenation was not ecdysone oxidase, a
      soluble enzyme found in peripheral tissues of many arthropods but it presented
      strong similarities with 3beta-hydroxysteroid dehydrogenase enzymes from
      vertebrates: it was membrane-bound and NAD+-dependent. Moreover, a NADH-dependent
      3beta-reduction of several 3-oxo-ecdysteroids was obtained using the same
      microsomal fraction (100,000 x g pellet) of Y-organs, indicating that the
      reaction might be reversible. As this activity was specific of molting glands, we
      hypothesize that there is at least one 3beta-hydroxysteroid dehydrogenase enzyme
      involved in the biosynthetic pathway of ecdysteroids.

PMID- 9140087
TI  - Evidence for an important functional role of intracellular loop II of the
      lutropin receptor.
AB  - The lutropin receptor (LHR) is a G protein-coupled receptor in which high
      affinity ligand binding occurs to the relatively large extracellular N-terminal
      domain. Various portions of the receptor have been mapped for their relative
      importance in localization and in hormone-mediated signaling. There is, however,
      a paucity of information available on the intracellular loops (ICL), where, along
      with the C-terminal cytoplasmic tail, G protein coupling is expected to occur.
      Site-directed mutagenesis was used to investigate the role of several conserved
      ionizable groups and one tyrosyl residue in ICLs I-III of the rat LHR. The pSVL
      expression vector, containing the LHR cDNA (wild-type and mutants), was
      transiently transfected into COS-7 cells, and human choriogonadotropin (hCG)
      binding and hCG-mediated cAMP production were determined. Several point mutants
      of amino acid residues in ICL II were prepared and characterized with the
      following results: replacements of Lys-455 and of His-460 with Glu gave mutant
      LHRs that failed to localize or fold properly at the cell surface as evidenced by
      the lack of significant binding to intact cells, although hCG binding could be
      detected in broken cell preparations, and a neighboring Arg-459 --> Glu
      replacement had no apparent effect on receptor trafficking, hCG binding or hCG
      mediated cAMP-production. A reversal mutant in ICL II in which Glu-441, at the
      boundary of transmembrane helix III and ICL II, and His-460, at the interface
      between ICL II and transmembrane helix IV, were interchanged, exhibited hCG
      binding to intact cells, but the maximal cAMP level at high concentrations of
      ligand was less than that obtained with COS-7 cells transfected with wild-type
      LHR. The total number of cell surface receptors determined with the reversal
      mutant was less than that found with wild-type LHR. This difference, however, is
      not believed to be responsible for the reduced signaling, since maximal cAMP
      responses to hCG were obtained with comparable receptor densities of wild-type
      and various mutant LHRs. Other single replacements in ICL I, Lys-368 --> Glu and
      to Gln, and in ICL III, Arg-526 --> Glu and Tyr-528 --> Ser, resulted in mutant
      LHRs with characteristics of wild-type LHR in trafficking, hCG binding and hCG
      mediated cAMP production. These findings suggest an important functional role of
      several amino acid residues in ICL II of LHR.

PMID- 9140088
TI  - Obesity, diabetes and functions for proopiomelanocortin-derived peptides.
AB  - Melanocortin peptides (adrenocorticotropin (ACTH), alpha-,beta-, and gamma
      melanocyte stimulating hormone (MSH), and fragments thereof) derived from
      proopiomelanocortin (POMC) have a diverse array of biological activities, many of
      which have yet to be fully elucidated. The recent cloning of a family of five
      distinct melanocortin receptors through which these peptides act has provided the
      tools to further our understanding of melanocortin peptide functions. Early work
      on melanocortin peptides focused on their roles in pigmentation, adrenocortical
      function, the immune, central and peripheral nervous systems. Although
      melanocortin peptides have long been known to affect lipolysis, characterisation
      of the melanocortin receptors has opened up several lines of evidence for
      important roles in the development of obesity, insulin resistance and type II
      diabetes. We present here a review of the current evidence for melanocortin
      peptides playing such a role, and based on this evidence, a model for
      melanocortin peptides and their receptors in maintaining energy balance.

PMID- 9140086
TI  - A sensitive reverse transcriptase polymerase chain reaction assay for measuring
      the effects of dehydration and gestation on rat amounts of vasopressin and
      ocytocin mRNAs.
AB  - This study describes a competitive reverse transcriptase polymerase chain
      reaction (RT-PCR) method for assaying the amounts of vasopressin (AVP) and
      ocytocin (OT) mRNAs in the rat hypothalamus and uterus. Despite the low
      concentrations of these mRNAs, the RT-PCR method readily measured both AVP and OT
      mRNAs in the same sample. A common internal standard for both reactions was
      designed to quantify the reaction. Both AVP and OT mRNAs were readily quantified
      in a 75 ng sample of total RNA from the hypothalamus. Water deprivation
      stimulated AVP mRNA production 3-fold and OT mRNA production 1.7-fold in the
      hypothalamus. Gestation only influenced the amount of OT mRNA in the hypothalamus
      (3-fold increase) and uterus (38-fold increase). The amount of AVP mRNA in the
      hypothalamus remained unchanged and no AVP mRNA was detected in the uteri of
      either non-pregnant or pregnant rats. This competitive RT-PCR is a powerful tool
      that provides rapid and precise assays of AVP and OT mRNAs.

PMID- 9140089
TI  - Adenylyl cyclases: structure, regulation and function in an enzyme superfamily.

PMID- 9140090
TI  - Requirement for surface aminopeptidase activities during development of CD8+
      fetal thymocytes.
AB  - The role of surface aminopeptidases (APs), enzymes that cleave amino-terminal
      residues from polypeptide chains, in the development of fetal thymocytes was
      studied using a murine fetal thymic organ culture (FTOC) model. FTOC AP activity
      was demonstrable for various amino acid-p-nitroanilide substrates, and specific
      inhibitors of AP (amastatin and bestatin) inhibited enzymatic activity. AP
      activity decreased from Day 4 to Day 7 in FTOC. Inhibition of AP activity during
      thymic development by FTOC in the presence of bestatin caused a significant
      selective decrease in the percentage of CD8+ cells (both CD4+CD8+ and CD4-CD8+).
      Bestatin did not downregulate expression of CD8 by a mature CD8+ T cell clone.
      These data suggest that APs are involved in the development of thymocytes
      expressing CD8.

PMID- 9140091
TI  - Molecular cloning and comparative analysis of the rhesus macaque costimulatory
      molecules CD80 (B7-1) and CD86 (B7-2).
AB  - To facilitate analysis of the role of costimulatory molecules in a nonhuman
      primate model, we cloned and sequenced the CD80 (B7-1) and CD86 (B7-2)
      costimulatory molecules from rhesus macaques. Rhesus CD80 and CD86 were highly
      homologous to their human counterparts, with overall amino acid homologies of
      greater than 90%, and were specifically recognized by murine antihuman CD80 or
      CD86 monoclonal antibodies. Stable cell lines expressing rhesus CD80 or CD86
      induced proliferation of suboptimally activated CD4+ T cells and transcription of
      cytokine mRNA. Both CD80 and CD86 were able to provide costimulation for
      interferon-gamma and IL-2 synthesis by rhesus CD4+ T cells, but CD80
      costimulation also resulted in synthesis of IL-4 and IL-10. The high degree of
      homology between the rhesus and the human CD80 and CD86 molecules should
      facilitate analysis of therapeutic interventions directed at this costimulatory
      pathway in nonhuman primates.

PMID- 9140092
TI  - T cell progenitors in the murine fetal liver: differences from those in the adult
      bone marrow.
AB  - We compared the T cell generation from progenitors (T-progenitors) in the fetal
      liver (FL) with those in the fetal thymus (FT) and adult bone marrow (BM) by
      culturing these T-progenitors with hematopoietic cell-depleted FT lobes. As has
      previously been noted, 15-20 days were required for BM T-progenitors to give rise
      to CD4+ and/or CD8+ T cells. In marked contrast, only 7-10 days were enough for
      FL T-progenitors to produce those T cells. The kinetics of T cell differentiation
      from sorted c-kit+Lin- FL cells were quicker than those of BM cells and slower
      than those of FT cells. These results have indicated that prethymic FL T
      progenitors are distinct from both prethymic BM T-progenitors and thymic FT T
      progenitors in reference to their differentiational stage. Moreover, these FL
      type T-progenitors exist in the liver during fetal age from Day 12 of gestation
      but not in the bone marrow of 1-week-old neonatal mice, suggesting that the fetal
      liver as a hematopoietic organ could induce the early T cell differentiation of
      progenitor cells.

PMID- 9140093
TI  - Depletion of T lymphocytes with immunotoxin retards the progress of experimental
      allergic encephalomyelitis in rhesus monkeys.
AB  - FN18-CRM9 is an anti-rhesus anti-CD3 immunotoxin that can transiently deplete T
      cells to 1% of initial values in both the blood and lymph node compartments and
      can induce long-term tolerance to mismatched renal allografts. We have
      investigated the ability of this immunotoxin to interdict the course of an
      experimental rhesus T-cell-driven autoimmune disease, experimental allergic
      encephalomyelitis (EAE) induced by myelin basic protein. Monkeys showing CSF
      pleocytosis were then treated with FN18-CRM9 alone or in combination with cranial
      irradiation (325 or 650 cGy). EAE in nontreated control monkeys progressed
      rapidly. Paralysis occurred 4-6 days after CSF pleocytosis. Paralysis was either
      delayed or never occurred in treated monkeys, and histopathology revealed few
      inflammatory plaques that were notable for their low or absent T cell content.
      While T cells repopulate in the periphery posttreatment, they do not return to
      the CNS in large numbers, suggesting that the newly repopulated T cells have lost
      their previously acquired CNS homing capability. Anti-CD3 immunotoxin may be
      useful in treating clinical T-cell-driven autoimmune diseases such as rheumatoid
      arthritis and multiple sclerosis.

PMID- 9140094
TI  - Interactions between autologous CD4+ and CD8+ T lymphocytes and human squamous
      cell carcinoma of the head and neck.
AB  - The autotumor (AuTu)-specific cytolytic T lymphocyte (CTL) line established from
      the peripheral blood of a patient with oral squamous cell carcinoma (Cancer Res.
      53, 1461, 1993) contained >95% of CD8+ and <5% of CD4+ T cells. This CTL line was
      infected with Herpesvirus saimiri to increase its life span in culture. Two
      transformed T cell sublines were obtained: the monoclonal CD4+ line (TCR Vbeta2+
      V alpha15+) and the oligoclonal CD8+ line (TCR Vbeta6+, Vbeta7+ and Vbeta9+) both
      of which were maintained in culture for >6 months without AuTu restimulation and
      which did not produce any virus. The virus-transformed and untransformed T cell
      lines were compared for phenotypic and functional characteristics, including the
      ability to kill AuTu, induce expression of the major histocompatibility complex
      (MHC) antigens on AuTu, and respond to AuTu by cytokine production and/or
      proliferation. The H. saimiri-transformed CD4+ T cells expressed higher levels of
      surface adhesion molecules and CD45RO than untransformed cells and lysed AuTu by
      inducing DNA fragmentation as well as necrosis. This lysis was inhibited by
      antibodies to CD4 but not to class I or II MHC molecules. The CD4+ T cells
      produced IL2, TNF-alpha, and GM-CSF and proliferated in response to AuTu. They
      induced and sustained proliferation of CD8+ T cells in cocultures with AuTu.
      Supernatants obtained from cocultures of the CD4+ T cells with AuTu also induced
      proliferation of the CD8+ T cell line. In contrast, the H. saimiri-transformed
      CD8+ T cells did not kill AuTu or release cytokines in response to AuTu. However,
      upon pretreatment of AuTu with IFN-gamma to increase expression of MHC antigens,
      these T cells regained the ability to recognize and kill AuTu targets.
      Coincubation of AuTu with the CD4+ or CD8+ T cells significantly augmented
      expression of class I and II MHC antigens on AuTu. These data indicate that H.
      saimiri-transformed tumor-reactive T cell lines provide a useful model of
      interactions between immune effector cells and AuTu, and that CD4+ T cells play a
      critical role in the regulation of immune responses to squamous cell carcinoma of
      the head and neck.

PMID- 9140095
TI  - Quantitative but not qualitative variation in MHC class II alters CD4 interaction
      and influences T cell repertoire formation.
AB  - The influence of the interaction between CD4 and MHC class II molecules on
      selection of the T cell repertoire was studied in transgenic mice expressing
      human or human/mouse hybrid MHC class II beta chains. Either wild-type DR beta
      chains (DR1 beta) or hybrid beta chains comprising the beta1 domain of DR and the
      beta2, transmembrane, and intracytoplasmic domains of I-E (DRbeta 1Ebeta2) were
      introduced into and expressed in transgenic mice as a heterodimer with endogenous
      I-E alpha. Mice expressing low levels of DR1beta:I-E alpha or those expressing
      low or higher levels of the hybrid DRbeta 1Ebeta2:I-E alpha were studied.
      Immunization with a suboptimal dose of influenza nucleoprotein peptide exposed a
      fivefold lower frequency of DR-restricted, peptide-specific, IL-2-secreting T
      cells in the mice with low-level expression of DRbeta1 Ebeta2:I-E alpha when
      compared to mice expressing the same molecule at higher levels. The frequency in
      DRbeta wild-type mice was only twofold lower than that measured in mice with
      comparable levels of expression of DRbeta 1Ebeta2. These results suggest that
      positive selection is sensitive to quantitative variation in MHC class II
      density, unmasked when antigen is limiting, but is relatively insensitive to
      qualitative variation in the MHC class II: CD4 interaction.

PMID- 9140096
TI  - Prevention and suppression of autoimmune encephalomyelitis by EUK-8, a synthetic
      catalytic scavenger of oxygen-reactive metabolites.
AB  - Breakdown of T cell tolerance to self-myelin basic protein induces an autoimmune
      process that leads to demyelination of the central nervous system (CNS) in
      multiple sclerosis (MS) patients. While the autoimmune disease is initiated by
      antigen-specific autoreactive T cells, there is accumulating evidence that CNS
      injury is essentially mediated by CNS-infiltrating inflammatory cells. In
      addition, it is established that activated macrophages and polymorphonuclear
      cells contribute to tissue damage in several inflammatory diseases by releasing
      highly reactive oxygen metabolites. It was therefore possible that demyelination
      associated with MS results from oxidative injury caused by a cascade of oxygen
      reactive metabolites produced by CNS-infiltrating activated macrophages and other
      inflammatory cells. To address this question, we tested the effect of a synthetic
      catalytic scavenger of oxygen radicals, EUK-8, on experimental allergic
      encephalomyelitis (EAE) in mice, the animal model for MS in humans. We observed
      that repeated injection of EUK-8 starting at the time of EAE induction delayed
      the onset and markedly reduced the severity of the disease. Strikingly, all EUK-8
      treated mice completely recovered after 40 days. In addition, we showed that
      posttreatment with EUK-8 4 days after EAE induction also resulted in a
      significant amelioration of EAE disease. These results indicate that oxygen
      metabolites secreted by inflammatory cells at the site of tissue destruction play
      a major role in the induction and presumably the perpetuation of the autoimmune
      disease. This study also suggests that treatment with oxygen metabolites
      scavengers may represent a novel and promising strategy to prevent the onset and
      to block the course of ongoing autoimmune encephalomyelitis and other
      inflammatory autoimmune diseases.

PMID- 9140098
TI  - Determinant selection for T-cell tolerance in HEL-transgenic mice: dissociation
      between immunogenicity and tolerogenicity.
AB  - The induction of T-cell tolerance to self-antigens has been extensively
      characterized for immunodominant (ID) regions. However, tolerance toward other
      minor self-determinants has received less attention. In the H-2(d) haplotype, HEL
      contains a single ID determinant (region 102-120) presented by I-E(d) MHC class
      II molecules. The present study evaluates the role of subdominant and cryptic HEL
      regions in maintaining tolerance. We have generated a mutated HEL antigen, HEL
      mu, whose ID region does not bind to I-E(d). Lymph node cells from HEL-immunized
      mice proliferated strongly to HEL mu in vitro. Two new stimulatory regions common
      to HEL and HEL mu were uncovered. They are produced during antigen processing and
      prime specific T lymphocytes. HEL-Tg mice were tolerant to these determinants,
      thus confirming their in vivo presentation. These HEL regions were as tolerogenic
      as the HEL ID determinant, despite their poor immunogenicity. These results
      demonstrate that there is not always a correlation between tolerogenicity and
      immunogenicity, a finding that may be critical for understanding T-cell
      tolerance.

PMID- 9140097
TI  - Iscoms containing purified Quillaja saponins upregulate both Th1-like and Th2
      like immune responses.
AB  - The immune stimulating complex (iscom) is built up by antigen, cholesterol,
      phospholipids, and adjuvant active Quillaja saponins. Previous studies have shown
      that iscoms containing Quil A (a semipurified preparation of saponins)
      efficiently induce antibody and cell-mediated immune responses. In this study, we
      demonstrate that iscoms containing a mixture of two purified low toxicity
      Quillaja saponin fractions (ISCOPREP 703) are able to upregulate both Th1-like
      and Th2-like immune responses. Thus, ovalbumin (OVA) iscoms induced higher levels
      of antigen-specific IgG1 and IgG2a antibodies and increased the production of
      both IFN-gamma and IL-4 compared with OVA administered without adjuvant. In
      contrast, OVA formulated in Al(OH)3 elicited IgG1 and IgE antibodies and primed
      spleen cells producing IL-4 and IL-10, suggesting the activation of primarily Th2
      like cells. These findings underline that adjuvants are able to alter the
      character of immune responses and may be used to generate responses with desired
      properties.

PMID- 9140099
TI  - Natural killer cell as the effector which mediates in vivo apoptosis in AK-5
      tumor cells.
AB  - AK-5 tumor cell death is mediated by natural killer cells through necrosis
      (perforin mediated) and apoptosis. Apoptosis is the mechanism which operates in
      immune animals in vivo. We have identified natural killer (NK) cell as the
      effector cell which induces apoptosis leading to tumor cell death in vivo. Naive
      NK cell which is unable to kill the AK-5 tumor cell can be activated with IL-2/IL
      12 to make it capable of inducing apoptosis in tumor cells. NK cells from tumor
      rejected animals show higher expression of Fas ligand and serine esterase
      granzyme B. In addition, NK cell-mediated apoptosis in AK-5 cells is totally
      abolished when effector cells are treated with anti-NKR-P1 mAb 3.2.3 and
      complement. NK cell-mediated apoptotic activity is inhibited in bcl-2 transfected
      tumor cells; however, the cytotoxic activity (perforin-mediated) remains
      unaffected. These observations suggest an important role for activated NK cells
      in inducing tumor cell death through necrosis (ADCC) and apoptosis leading to
      spontaneous regression of the AK-5 tumor in syngeneic animals.

PMID- 9140101
TI  - National Influenza Surveillance 1996.
AB  - In 1996 data from laboratories, general practitioners and a national employer
      were combined to detect trends in influenza activity in Australia. An epidemic of
      influenza A (H3N2) was recorded. Little influenza B activity was noted throughout
      the winter months, however the number of laboratory reports of influenza B rose
      in the last quarter of the year. Influenza activity was reflected in the
      consultation rates recorder by sentinel general practitioner reporting schemes.
      Of particular note was the Tropical Influenza Surveillance in the Northern
      Territory which demonstrated a bimodal epidemic pattern. There was no apparent
      trend in national absenteeism rates recorded by a national employer.

PMID- 9140100
TI  - Antigen-presenting function of murine gonadal epithelial cell lines.
AB  - Murine Leydig (TM3) and Sertoli (TM4) cell lines were studied as nonprofessional
      antigen-presenting cells using the antigen model of human choriogonadotropin (hCG
      alpha/beta) and specific T-cell hybridomas. Both cell lines were treated with IFN
      gamma to induce I-A(d) and I-E(d) molecules expression. Only the TM3 cell line,
      which expressed MHC-class II molecules upon IFN-gamma stimulation, was able to
      uptake, process, and present the human choriogonadotropin beta subunit to related
      T-cell hybridomas. Interestingly, the TM3 cell line was incapable of presenting
      the human choriogonadotropin alpha subunit, the presentation of which, by
      classical APC, is highly efficient. Using T-cell hybridomas directed against the
      immunogenic regions of hCG alpha/beta previously described in BALB/c mice, we
      showed that the TM3 cell line generated a narrower peptide repertoire than
      classical APC (i.e., B cells, macrophages, and dendritic cells). This
      experimental system suggests that Leydig cells could initiate, in vivo, an
      autoimmune process directed against gonadal tissues. In particular, such a
      mechanism has been evoked in experimental autoimmune orchitis.

PMID- 9140102
TI  - An outbreak of influenza B among workers on an oil rig.
AB  - An outbreak of influenza B occurred in December 1996 on an oil rig in Darwin
      Harbour. The outbreak affected 56% of the workers on the rig. An outbreak in
      December is outside the usual Australian influenza season of June to September,
      but is consistent with other tropical regions, where outbreaks can occur
      throughout the year. Influenza vaccination could prevent similar outbreaks in
      confined workplaces.

PMID- 9140103
TI  - Communicable diseases surveillance.

PMID- 9140104
TI  - No evidence of mutation in the human PTC gene, responsible for nevoid basal cell
      carcinoma syndrome, in human primary squamous cell carcinomas of the esophagus
      and lung.
AB  - The high frequency of loss of heterozygosity that has been observed on the distal
      region of the long arm of chromosome 9 in squamous cell carcinomas of esophagus,
      lung, uterus, and head and neck indicates the presence of a tumor suppressor
      gene(s) in this region. To investigate the possible role of the PTC gene on
      chromosome 9q22.3, that was identified as the cause of nevoid basal cell
      carcinoma syndrome, during carcinogenesis in esophagus and lung, we examined 20
      esophageal squamous cell carcinomas and 10 squamous cell carcinomas of the lung
      for mutations in any coding exon of PTC. Using single-strand conformation
      polymorphism and direct sequencing, we detected no mutations other than two non
      deleterious polymorphisms. Our results suggest that inactivation of some tumor
      suppressor gene(s) on 9q other than PTC contributes to the development of
      squamous cell carcinomas in these tissues.

PMID- 9140105
TI  - Concomitant presence of p16/cyclin-dependent kinase 4 and cyclin D/cyclin
      dependent kinase 4 complexes in LNCaP prostatic cancer cell line.
AB  - The cyclin D/cyclin-dependent kinase (CDK)/CDK-inhibitory proteins/retinoblastoma
      protein (pRb) pathway is hypothesized to control the G1-S check point. The role
      of this pathway is reported to be different depending on the status of pRb. In
      the present study, we examined nine human urological tumor cell lines. Cells
      lacking functional pRb expressed p16, instead of forming cyclin D/ CDK4 complex.
      In the LNCaP prostatic cancer cell line, however, both p16/CDK4 and cyclin D/
      CDK4 complexes were present independently, probably because of partial loss of
      pRb. In view of the concomitant presence of the incompatible complexes, LNCaP
      should provide us with a valuable model for the study of this pathway in cancer
      cells.

PMID- 9140106
TI  - Suppression of nitric oxide production in lipopolysaccharide-stimulated
      macrophage cells by omega 3 polyunsaturated fatty acids.
AB  - Although nitric oxide (NO) is an important biological mediator, its excessive
      production in inflammation is thought to be a causative factor for cellular
      injury and, over the long term, cancer. In the present study, the effects of
      several fatty acids on NO production in murine macrophage cell line RAW264 cells
      stimulated with lipopolysaccharide were examined. Suppression of NO production
      was observed with the omega 3 polyunsaturated fatty acids (PUFAs),
      docosahexaenoic acid, eicosapentaenoic acid and alpha-linolenic acid, in a dose
      dependent fashion. In contrast, no inhibition was observed with omega 6 PUFA
      (linoleic acid), omega 9 PUFA (oleic acid) or a saturated fatty acid (stearic
      acid). Western and northern blot analyses suggested that suppression of the
      induction of inducible NO synthase gene expression is responsible for the
      inhibition of NO production by omega 3 PUFAs. The inhibitory effect of omega 3
      PUFA on NO production in activated macrophages could contribute to their cancer
      chemopreventive influence.

PMID- 9140107
TI  - Dose-dependent induction of both pepsinogen-altered pyloric glands and
      adenocarcinomas in the glandular stomach of C3H mice treated with N-methyl-N
      nitrosourea.
AB  - The dose-response relation for the appearance of pepsinogen isozyme 1 (Pg 1)
      altered pyloric glands (PAPG) and the related induction of adenocarcinomas were
      examined in male C3H mice given N-methyl-N-nitrosourea (MNU) in their drinking
      water at the concentration of 120 ppm (group 1), 60 ppm (group 2), 30 ppm (group
      3) or 0 ppm (group 4) for 30 weeks and then normal tap water. Animals were killed
      at weeks 10, 30 and 42. Adenomatous hyperplasias and adenocarcinomas were noted
      from week 30 and their induction was dose-dependent at week 42. Almost all cells
      of pyloric gland cell type in those lesions had little or no
      immunohistochemically demonstratable Pg 1 content, as was also the case for the
      cells in PAPG, whose numbers per 100 normal-appearing pyloric glands were found
      to be MNU dose-dependent at all experimental time points. The numbers of PAPG at
      week 10 significantly correlated with the incidences of adenomatous hyperplasias
      and adenocarcinomas at week 42. Investigation of proliferation by
      immunohistochemical detection of bromodeoxyuridine (BrdU) labeling in the PAPG at
      week 10 demonstrated elevation (P < 0.05) as compared to normal pyloric glands.
      Intestinal metaplasia was not a feature in the present experiment and the results
      suggest that in mice, PAPG might be a preneoplastic lesion involved in gastric
      chemical carcinogenesis.

PMID- 9140108
TI  - Strain differences in sensitivity to the promoting effect of sodium L-ascorbate
      in a two-stage rat urinary bladder carcinogenesis model.
AB  - Rat strain differences in sensitivity to the promoting effect of sodium L
      ascorbate (SA) on the development of urinary bladder tumors were investigated. In
      experiment 1, WS/Shi (WS), ODS/Shiod/od (ODS), and LEW/Crj (LEW) rats were
      initiated with 0.05% N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) in their
      drinking water and subsequently given basal Oriental MF diet (M) with or without
      a 5% SA supplement. In LEW rats the SA treatment increased the induction of
      neoplastic lesions in the urinary bladder, whereas WS and ODS animals proved
      unresponsive to its promoting effects. In experiment 2, WS and F344 rats were
      maintained on two kinds of commercial basal diets, M and CLEA CA-1 (C), during
      administration of SA, since dietary factors can influence promoting effects.
      Feeding M during the promotion period in F344 rats yielded significantly more
      neoplastic lesions than feeding C, but in WS rats no such dietary influence was
      apparent. In experiment 3, strain differences in biosynthesis of alpha-2u
      globulin (alpha 1a-g) were assessed because both alpha 2a-g in the urine and
      administration of sodium salts of organic acids such as SA have been reported to
      be involved in tumor promotion. Immunohistochemical analysis of renal tubules and
      Western blotting analysis of urine revealed the presence of alpha 2a-g in all
      three strains examined. These data suggest that differences in susceptibility to
      promotion are due to genetic factors rather than dietary factors and the ability
      to synthesize alpha 2a-g.

PMID- 9140110
TI  - Infrequent overexpression of p53 protein in Epstein-Barr virus-associated gastric
      carcinomas.
AB  - Epstein-Barr virus (EBV) infection was studied in a total of 412 patients with
      poorly differentiated gastric adenocarcinoma by in situ hybridization for EBV
      encoded small RNA. EBV-specific RNA was detected in tumor cell nuclei of 83
      (20.1%) of 412 gastric carcinomas, of which 60 were histologically subclassified
      as gastric carcinoma with lymphoid stroma (GCLS). All EBV-positive gastric
      carcinomas as well as 90 randomly selected EBV-negative gastric carcinomas were
      further studied for p53 protein expression by immunohistochemistry. The
      overexpression of p53 protein was demonstrated in only 7 (8.4%) of 83 EBV
      positive gastric carcinomas. This was in marked contrast to the frequency of
      34.4% in EBV-negative gastric carcinomas. In addition, a few p53-positive nuclei
      were characteristically scattered in the tumors of many EBV-positive GCLS, but
      this was not regarded as p53 overexpression arising from mutation of the gene.
      Our findings suggested that EBV-associated gastric carcinomas may arise through a
      different mechanism from other types of gastric carcinomas without EBV infection.

PMID- 9140109
TI  - Intragenic Tsc2 somatic mutations as Knudson's second hit in spontaneous and
      chemically induced renal carcinomas in the Eker rat model.
AB  - We searched for the rat homologue of the human tuberous sclerosis (TSC2) gene
      mutations in loss of heterozygosity (LOH)-negative Eker rat renal carcinomas
      (RCs) by polymerase chain reaction-single-strand conformational polymorphism (PCR
      SSCP) analysis using 45 primer sets covering all 41 coding exons and one leader
      exon including splicing donor/acceptor sites. We have identified intragenic
      somatic mutations in 7 of 21 spontaneous RCs, including one cell line (33%), and
      in 3 of 9 (33%) N-ethyl-N-nitrosourea (ENU)-induced LOH-negative RCs.
      Interestingly, five mutations in the spontaneous RCs were either deletion or
      duplication (5/7 = 71%). In contrast, all three in ENU-induced RCs were base
      substitutions (3/3 = 100%), as expected. Thus, a qualitative difference in the
      second hit might exist between spontaneous and ENU-induced mutations (e.g.,
      deletion or duplication versus point mutation). By a direct cloning approach
      utilizing the restriction length difference caused by germline insertional
      mutation or reverse transcriptase-PCR analysis in two applicable cases, we could
      clearly show the presence of intragenic somatic mutations in the second copy
      (wild-type) of the Tsc2 gene. This is the first demonstration at the DNA sequence
      level of the validity of Knudson's two-hits hypothesis in the Tsc2 gene.

PMID- 9140111
TI  - Inhibition by protein kinase C inhibitor of expression of leukocyte function
      associated antigen-1 molecules in rat hepatoma AH66F cells.
AB  - To examine the mechanism of inhibition by protein kinase C (PKC) inhibitors of
      the adhesion of highly malignant hepatoma AH66F cells to the mesentery-derived
      mesothelial cell (M-cell) layer through leukocyte function-associated antigen-1
      (LFA-1)/intercellular adhesion molecule-1, the effects of a PKC inhibitor, NA
      382, on the expression of LFA-1 molecules in AH66F cells were examined and
      compared with those in thymocytes from normal rats. NA-382 inhibited the adhesion
      of AH66F cells to the M-cell layer and the expression of LFA-1 on the membrane of
      the hepatoma cells after treatment for more than 24 h. It was confirmed that
      AH66F cells express similar mRNAs for LFA-1 subunits to those of thymocytes, and
      their levels were also decreased after treatment with NA-382. On the other hand,
      the LFA-1 mediated adhesion and the expression of both protein and mRNA for LFA-1
      subunits in thymocytes were not changed by the PKC inhibitor. These results
      suggest that the expression of LFA-1 molecules in AH66F cells may be regulated by
      PKC via quite different mechanisms from those in normal lymphocytes.

PMID- 9140112
TI  - Immunoreaction at 43 kDa with anti-ubiquitin antibody in breast neoplasms.
AB  - Protein ubiquitination has been implicated in ATP-dependent protein turnover and
      normal cell proliferation. To investigate whether the ubiquitin-mediated system
      is functionally involved in the cancerous state, we examined changes in protein
      ubiquitination in 52 surgically resected primary breast tumors.
      Immunohistochemically, ubiquitin (Ub) was identified in the cytoplasm of cancer
      cells, which were stained more strongly than adjacent normal ductal epithelium.
      Corresponding immunoblot analysis of normal and neoplastic regions of human
      breast showed that the immunoreaction for Ub at about 43 kDa was increased in all
      of the tumors (100%), regardless of the clinical stage or histologic grade. This
      protein, which gave a single spot on two-dimensional gel electrophoresis, had
      partial amino acid sequences which were identical to those of actin family
      members. Our results suggest that ubiquitination of this 43-kDa protein may be
      involved in the carcinogenesis or biological characteristics of human breast
      neoplasms.

PMID- 9140113
TI  - Bacillus Calmette-Guerin enhances production and secretion of type IV
      collagenases in peripheral blood mononuclear cells.
AB  - Intravesical administration of bacillus Calmette-Guerin (BCG) is an effective and
      widely accepted treatment for superficial bladder cancer. Rapid progression of
      the disease after BCG therapy, however, has been reported in some cases
      refractory to the treatment. We examined whether BCG treatment and coexistence of
      peripheral blood mononuclear cells (PBMCs) alter the invasive potential of
      bladder cancer cells. Production and secretion of two type IV collagenases,
      matrix metalloproteinase (MMP) 2 and MMP 9, by PBMCs from five healthy donors or
      bladder cancer cells (T24, JTC 30, and JTC 32) were evaluated by gelatin
      zymography, western blot analysis, and northern blot analysis. Invasion of
      bladder cancer cells was also examined using reconstituted basement membrane
      (Matrigel). BCG (5, 50, and 500 micrograms/ml) had no effect on secretion of MMP
      2 and MMP 9 by bladder cancer cells, but increased the production and secretion
      of MMP 9 by PBMCs in a dose-dependent manner. The coexistence of PBMCs increased
      invasion of T24 cells and BCG further enhanced the invasion. Thus, BCG promotes
      invasion of bladder cancer cells under certain conditions. An increase in the
      secretion of MMP 9 by PBMCs may account in part for the effect.

PMID- 9140115
TI  - Efficient retrovirus-mediated cytokine-gene transduction of primary-cultured
      human glioma cells for tumor vaccination therapy.
AB  - In order to realize a novel vaccination treatment for malignant gliomas using
      tumor cells genetically modified to express certain cytokines, it is essential to
      achieve an efficient gene transduction into primary cultured cells. We
      investigated the feasibility of preparing a glioma vaccine through retrovirus
      mediated gene transduction. Glioma cells were cultured primarily from surgically
      resected tumor tissues of six patients. We obtained more than 1000-fold
      proliferation of cultures within eight weeks in all six cases. In vitro infection
      with a recombinant retrovirus GKlacZ carrying an Escherichia coli beta
      galactosidase marker gene resulted in over 65% gene transfer to the primary
      cultured glioma cells. Further enrichment (approximately 90%) of transduced cells
      was possible by employing repeated infections or using vectors with neo' marker
      gene. Two cytokine genes, granulocyte-macrophage colony-stimulating factor and
      interleukin-4, were introduced into glioma cells by sequential transduction with
      two single-expression GK vectors. The transduced glioma cells produced high
      levels of both cytokines. We also evaluated simultaneous introduction of two
      genes with double-expression GK vectors containing internal ribosomal entry site
      (IRES) or internal promoter (PGK). Although the cells transduced with double
      expression vectors secreted both cytokines, the level of the gene product
      following IRES or PGK was 10 times lower than that of the upstream gene product.
      The transduced cells retained cytokine secretion in vitro for 14 days after 100
      Gy irradiation. Our data indicate the feasibility of retrovirus-mediated
      preparation of gene-modified tumor vaccines from clinical glioma materials, which
      could be useful for potentiating antitumor immunity in glioma patients.

PMID- 9140114
TI  - Induction of specific cytotoxic T lymphocytes against autologous brain tumor by
      crossreactive allo-tumor cell stimulation.
AB  - Cytotoxic T lymphocytes (CTL) against autologous malignant brain tumor were
      generated in peripheral blood lymphoid cells (PBL) prepared from a patient with a
      malignant brain tumor by stimulation of the cultured PBL for 7 days with
      attenuated crossreactive malignant melanoma (MM2) cells pretreated with mitomycin
      C. The crossreactive MM2 cells were effective for antigen stimulation for CTL
      induction in place of autologous glioblastoma cells, which are difficult to
      expand in culture. The optimal ratio between nylon wool-passed T lymphocytes and
      nylon wool-adherent accessory cells to induce CTL in the patient's PBL was found
      to be 25 to 1. In vitro-activated CTLs induced by MM2 were cytotoxic not only to
      MM2, but also to the autologous tumor cells in an HLA class I-restricted manner,
      and their surface phenotype was found to be CD3+ and CD8+. CTL therapy using
      cross-reactive allogeneic tumor cells as the stimulator could be clinically
      valuable to treat malignant brain tumors.

PMID- 9140116
TI  - Antitumor effects of 5'-deoxy-5-fluorouridine in combination with recombinant
      human interleukin 2 on murine colon carcinoma 26.
AB  - The antitumor activity of recombinant human interleukin 2 (rIL-2) in combination
      with 5'-deoxy-5-fluorouridine (doxifluridine; 5'-DFUR) against marine colon
      carcinoma 26 (Colon 26) was studied. BALB/c mice were treated daily for 15 days
      with 5'-DFUR, rIL-2 or both, beginning on day 7 after subcutaneous
      transplantation of Colon 26. While mice treated with 5'-DFUR or rIL-2 alone died
      of tumor growth with pulmonary metastases within 9 weeks posttransplantation, the
      survival time was significantly prolonged in mice treated with both 5'-DFUR and
      rIL-2. Most of the combination-treated animals showed the regression of local
      tumors and the inhibition of pulmonary metastasis. Histopathologically, many
      tumor cells were degenerated and necrotized, with marked infiltration of
      mononuclear cells including large granular lymphocytes (LGLs) with periodic acid
      Schiff-positive cytoplasmic granules. The cells were positive for CD3 epsilon,
      asialo GM1 and NK1.1. Spleen cells from the combination-treated mice showed high
      activities of natural killer (NK) cytotoxicity as well as growth inhibition of
      Colon 26 and Meth A fibrosarcoma in mice. The results suggest that the
      combination therapy of 5'-DFUR plus rIL-2 enhanced non-specific cytotoxicity of
      LGL/NK cells for Colon 26 in tumor-bearing mice and was effective in the
      inhibition of tumor growth.

PMID- 9140118
TI  - Application of image analysis and neural networks to the pathology diagnosis of
      intraductal proliferative lesions of the breast.
AB  - We studied whether a computer-assisted system using a combination of data
      collection by image analysis and analysis by neural networks can differentiate
      benign and malignant breast lesions. Forty-six intraductal lesions of the breast
      were studied by pathologists and by the computer-assisted system. Histological
      evaluation was performed independently by three pathologists, and the lesions
      were classified into pathologically malignant (n = 12), undetermined (n = 13),
      and benign (n = 21). Computerized nuclear image analysis was performed using the
      CAS200 (Cell Analysis Systems, Elmhurst, IL) system to obtain data on nuclear
      morphometric and textural features. A neural network was constructed using the
      morphometric and texture data obtained from teaching cases of malignant and
      benign lesions. Then data for unknown cases were classified by the constructed
      neural network into neural network-malignant (n = 11), -undetermined (n = 5), and
      -benign (n = 30). The agreement rate between the diagnosis by pathologists and
      judgment by the computer-assisted system was 75%, excluding pathologically
      undetermined lesions. There were four false-negative but no false-positive
      results. False-negative cases had nuclei that were quite different from those of
      the teaching cases. The agreement rate obtained using either morphometric data or
      texture data only was lower than that using a combination of both. Selection of
      appropriate teaching data and incorporation of both morphometric and textural
      parameters seemed important for obtaining more accurate results. The present data
      suggest that development of a computer-assisted histopathological diagnosis
      system for practical use may be possible.

PMID- 9140117
TI  - Antitumor activity of TZT-1027, a novel dolastatin 10 derivative.
AB  - Dolastatin 10, a pentapeptide isolated from the marine mollusk Dolabella
      auricularia, has antitumor activity. TZT-1027, a dolastatin 10 derivative, is a
      newly synthesized antitumor compound. We evaluated its antitumor activity against
      a variety of transplantable tumors in mice. Intermittent injections of TZT-1027
      were more effective than single or repeated injections in mice with P388 leukemia
      and B16 melanoma. Consequently, TZT-1027 shows schedule dependency. TZT-1027 was
      effective against P388 leukemia not only when administered i.p., but also when
      given i.v. However, although TZT-1027 given i.v. was active against murine solid
      tumors, TZT-1027 administered i.p. was ineffective against all the tumors tested
      with the exception of colon 26 adenocarcinoma. The i.v. injection of TZT-1027 at
      a dose of 2.0 mg/kg remarkably inhibited the growth of three murine solid tumors;
      colon 26 adenocarcinoma, B16 melanoma and M5076 sarcoma, with T/C values of less
      than 6%. The antitumor activities of TZT-1027 against these tumors were superior
      or comparable to those of the reference agents; dolastatin 10, cisplatin,
      vincristine, 5-fluorouracil (5-FU) and E7010. In experiments with drug-resistant
      P388 leukemia, TZT-1027 showed good activity against cisplatin-resistant P388 and
      moderate activity against vincristine- and 5-fluorouracil-resistant P388, but no
      activity against adriamycin-resistant P388. TZT-1027 was also effective against
      human xenografts, that is, tumor regression was observed in mice bearing MX-1
      breast and LX-1 lung carcinomas. TZT-1027 at 10 microM almost completely
      inhibited the assembly of porcine brain microtubules. Therefore, its mechanism of
      antitumor action seems to be, at least in part, ascribable to the inhibition of
      microtubule assembly. Because of its good preclinical activity, TZT-1027 has been
      entered into phase I clinical trials.

PMID- 9140120
TI  - Immunoreactivity of recombinant human glandular kallikrein using monoclonal
      antibodies raised against prostate-specific antigen.
AB  - The gene encoding human glandular kallikrein (KLK2) was expressed in Escherichia
      coli, and the corresponding protein (hK2) was produced by fermentation. The hK2
      was characterized by Western blotting and epitope map using monoclonal antibodies
      (MAbs) specific for another protease, prostate-specific antigen (PSA) with high
      structural identity (80%). MAbs that recognized three different epitopes were
      bound to hK2, representing 7 out of 23 MAbs tested. One epitope was localized to
      the sequence region around amino acid position 78, which is believed to be
      glycosylated in hK2. The affinities of MAbs recognizing hK2 were similar to those
      for PSA, suggesting that common epitopes seem to contain very conserved
      structures. The results may help in designing specific diagnostic assays for the
      assessment of prostate cancer.

PMID- 9140119
TI  - Effects of potent vitamin D3 analogs on clonal proliferation of human prostate
      cancer cell lines.
AB  - BACKGROUND: Management of prostate cancer that has spread outside of the prostate
      capsule is a difficult problem. Innovative, non-toxic approaches to the disease
      are required. New, relatively non-toxic vitamin D3 analogs have recently been
      synthesized. We report that several of these compounds have marked
      antiproliferative effects on prostate cells. METHODS: The clonal
      antiproliferative activity of five novel analogs of 1,25 dihydroxyvitamin D3
      [1,25(OH)2D3, (cmpd C)] as well as 1,25(OH)2D3 itself was tested on three human
      prostate cancer cell lines (PC-3, LNCaP, and DU-145). The analogs were 20-epi
      22oxa-24a,26a,27a-tri-homo-1 alpha,25(OH)2D3 (code name: KH 1060); 24a26a27a-tri
      homo-22,24-diene-1 alpha,25(OH)2D3 (code name: EB 1089); 1,25(OH)2-16ene-D3 (code
      name: HM); 1,25(OH)2-16ene-23yne-D3 (code name: V); 1,25(OH)2-20-epi-D3 (code
      name: MC 1288)]. RESULTS: With the parent compound [1,25(OH)2D3], the effective
      dose that inhibited 50% clonogenic growth of PC-3 and LNCaP was 10(-8)M and 7 x
      10(-9)M, respectively. For these prostate cancer cell lines, KH 1060 was the most
      potent analog by an order of 25- to 35-fold as compared to cmpd C. The second and
      third most potent analogs were HM and MC 1288. DU-145 was resistant to all the
      vitamin D3 analogs. The major side-effect of 1,25(OH)2D3 is the production of
      hypercalcemia. The relative inhibitory index (RII) was determined by comparing
      the antiproliferative activity of the analog to its ability to produce
      hypercalcemia in mice injected intraperitoneally every other day. The KH 1060 had
      the best RTI: 50- to 70-fold greater than 1,25(OH)2D3 for PC-3 and LNCaP,
      respectively. CONCLUSIONS: A trial of one or more of these innovative compounds
      should be considered for treatment of minimal residual disease of prostate
      cancer.

PMID- 9140121
TI  - Characterization of residual tumor cells following radical radiation therapy for
      prostatic adenocarcinoma; immunohistochemical expression of prostate-specific
      antigen, prostatic acid phosphatase, and cytokeratin 8.
AB  - BACKGROUND: Our knowledge about the nature and biological activity of tumor cells
      residing in the prostate gland after radical radiotherapy (RRT) is limited.
      METHODS: In the present study, residual tumor in core biopsies taken from 37
      patients after an average of 6.8 years follow-up after radiation, were
      investigated with immunohistochemistry for the biochemical markers prostate
      specific antigen (PSA), prostatic acid phosphatase (PAP), and the epithelial
      marker, cytokeratin 8 (CK8). RESULTS: Tumor cells were cytokeratin-positive in 33
      of 34 evaluable specimens (97%). PSA and PAP were expressed in the tumor cells in
      94% (34/36) and 81% (30/37) of cases, respectively. No significant correlation
      was observed between PSA/PAP expression and tumor grade after treatment.
      Endocrine treatment administered in addition to RRT in 12 of the 37 patients did
      not affect the expression of PSA or PAP. The expression of both biochemical
      markers was reduced after radiotherapy in 10 of the 12 cases for which pre- and
      post-treatment specimens were available. CONCLUSIONS: Tumor cells retain their
      epithelial characteristics immunohistochemically after radiation, though their
      morphology sometimes suggests an altered phenotype after treatment. PSA and PAP
      reactivity was demonstrated in tumor cells nearly 7 years after radiotherapy,
      which indicates that these cells maintain their biochemical integrity and protein
      synthesis to a certain extent. Furthermore, endocrine treatment did not abolish
      PSA or PAP expression in the tumor cells. Whether PSA and PAP immunoexpression
      provides independent prognostic information needs to be further investigated.

PMID- 9140122
TI  - Intra- and interobserver variability of MRI prostate volume measurements.
AB  - BACKGROUND: The Early Intervention Study, a placebo-controlled clinical trial,
      enrolled approximately 200 patients between age 45-65 years who had mild symptoms
      associated with early benign hyperplasia (BPH). Prostate volume was measured by
      magnetic resonance imaging (MRI) and read by the local radiologist, who was
      blinded to the treatment group but not to the sequence of MRI scans. In order to
      ascertain whether knowledge of the sequence of the MRI scans by the local
      radiologist was introducing bias in prostate volume changes, a single radiologist
      was selected to reread all MRI scans at the end of the study. METHODS: Each film
      was masked as to patient identity, study drug, and date. A new randomization
      schedule was prepared to blind the single reader to both sequence and treatment.
      The two sets of readings were compared. RESULTS: Accuracy was dramatically
      improved when defined as percentage of patients with a 20% or more decrease in
      prostate volume, from 14% to 0% in placebo patients, and from 38% to 29% in
      finasteride patients. The variability was significantly reduced (by 50%) when
      read by a single observer [1]. CONCLUSIONS: A single reader, blinded to time
      sequence as well as to therapy, improves the accuracy and precision of the
      measurements when compared to multiple readers, blinded only to drug therapy.

PMID- 9140123
TI  - Transforming growth factor-beta 3 is expressed in nondividing basal epithelial
      cells in normal human prostate and benign prostatic hyperplasia, and is no longer
      detectable in prostate carcinoma.
AB  - BACKGROUND: We investigated the role of the transforming growth factor beta (TGF
      beta) family in the neoplastic progression of the human prostate. METHODS:
      Expression of TGF-beta mRNA was measured by Northern blot analysis of tissue
      extracts, and TGF-beta protein by immunohistochemical analysis of tissue
      sections. Proliferating cells were detected by their expression of Ki-67 antigen.
      RESULTS: The level of TGF-beta 1 mRNA was equal among normal prostate, benign
      prostatic hyperplasia (BPH), and prostate carcinoma. TGF-beta 2 mRNA was not
      detectable, and TGF-beta 3 mRNA was expressed 20-fold lesion in carcinoma
      compared to BPH and normal prostate. TGF-beta 1 protein was expressed in the
      stromal cells in all three tissues and TGF-beta 3 protein in the basal layer of
      epithelial cells, but not in carcinoma. Proliferating epithelial cells fail to
      express TGF-beta 3. CONCLUSIONS: TGF-beta 1 and TGF-beta 3 are independently
      regulated, and carcinoma of the prostate is characterized by the loss of basal
      epithelial cells expressing TGF-beta 3.

PMID- 9140124
TI  - Use of neuroendocrine serum markers in the follow-up of patients with cancer of
      the prostate.
AB  - Neuroendocrine (NE) differentiation of prostatic adenocarcinomas has received
      increasing attention in recent years as a result of possible implications on
      prognosis and therapy. The incidence of NE cells in tumors has been reported from
      10% up to 100%. Several studies have shown chromogranin A (CgA) to be the most
      reliable serum marker of NE differentiation. We have followed 22 patients with
      prostatic adenocarcinoma over a 2-year period. The patients underwent a
      palliative transurethral resection of the prostate (TURP) because of urinary
      outflow obstruction. The prostatic tissue specimens were stained
      immunohistochemically using antibodies against CgA, chromogranin B (CgB), neuron
      specific enolase (NSE), thyroid-stimulating hormone (TSH), serotonin, and
      somatostatin. In addition, each specimen was stained with hematoxylin & eosin (H
      & E), and saffran for tumor grading. Blood samples were taken preoperatively and
      after 1, 3, 6, and 24 months. The serum values of CgA, CgB, pancreastatin (Pst),
      NSE, and prostate-specific antigen (PSA) were determined from each sample.
      Carcinomas with groups of CgA-positive cells had higher serum levels of CgA
      compared to carcinomas with no or only scattered CgA-positive NE cells. During
      the 2-year period, there were no statistical significant variations in serum
      levels of CgA, NSE, Pst, and PSA. However, there was a significant increase in
      serum levels of CgB during the same period, P = 0.002, possibly due to an
      increase in number of NE cells in tumor or to a relative increase in production
      of CgB in the NE cells.

PMID- 9140125
TI  - Aromatase in hyperplasia and carcinoma of the human prostate.
AB  - The expression and activity of aromatase was evaluated in 19 individuals with
      benign prostatic hyperplasia (BPH) and 26 prostatic carcinoma (PC) patients to
      elucidate the possible biological significance of in situ estrogen production in
      the development of human prostatic disorders. Marked aromatase immunoreactivity
      was observed in proliferative stromal cells, especially those around hyperplastic
      glands in 18 (95%) BPH patients and in stromal cells surrounding carcinomatous
      glands in 18 (69%) PC patient specimens. The percentage of aromatase-positive
      stromal cells did not differ between BPH and PC. No significant correlation was
      apparent between the percentage of aromatase-positive cells and either the extent
      of carcinoma differentiation or surgical stage in the PC patients. Quantitation
      of aromatase activity by the [3H] water assay yielded values of 27.23 +/- 6.87
      and 26.52 +/- 9.12 fmol/hr/mg of protein for BPH (nine patients) and PC (nine
      patients), respectively. Reverse transcriptase and polymerase chain reaction
      analysis revealed that the mean aromatase mRNA content was 1.671 +/- 0.82 and
      1.11 +/- 0.51 attomole/ng of total RNA (tRNA) for BPH (seven patients) and PC
      (four patients), respectively. There were no significant differences in aromatase
      activity or aromatase mRNA concentration between PC and BPH. The alternative use
      of multiple exons 1 of the aromatase gene was also examined. Predominant
      aromatase gene transcripts contained exon 1b in three of four of PC specimens and
      two of three BPH specimens examined, in contrast to the use of exon 1d previously
      described in normal prostate. Unlike breast and endometrium, therefore, aromatase
      expression in human prostate was not associated with malignancy. However,
      overexpression of aromatase, possibly attributable to abnormal gene regulation,
      may result in estrogen production in situ and play a role in the induction or
      development of human prostatic disorders.

PMID- 9140126
TI  - Ultrastructural localization of zinc ions in the rat prostate: an
      autometallographic study.
AB  - BACKGROUND: The prostate contains high amounts of free zinc ions which are
      excreted into the seminal fluid. The extra- and intracellular distribution of
      zinc ions using the highly specific autometallographical (AMG) method is
      described. METHODS: Prostates from sulfide-perfused rats were excised, and the
      ZnS crystals were silver-enhanced to sizes detectable by the electron and light
      microscope. RESULTS: AMGZnS grains were found primarily in the acinic lumen of
      the lateral lobes. The dorsal lobe stained only faintly, while the ventral lobe
      was void of grains. At ultrastructural levels, the presence of zinc ions was
      confined to apical secretory vesicles and lysosome-like structure of the
      epithelium of mainly the lateral lobes. CONCLUSIONS: We suggest a constant
      secretion of zinc ions from the epithelial cells into both the acinar lumen and
      the intercellular canaliculi, and that the zinc enriched secretory cells in the
      prostate belong to a system of glandular cells that uses zinc ions to aggregate
      macromolecules to be excreted.

PMID- 9140127
TI  - Intrinsic and extrinsic factors controlling benign prostatic growth.
AB  - This review will present a new concept on the etiology of the development of
      benign prostatic hyperplasia (BPH). Conventionally, two known etiological factors
      for the development of BPH have been aging and the presence of functional testes.
      Assignment of these two factors, although reasonable, has not been conducive to
      aid the research community to identify and isolate the patho-physiological agents
      that are directly responsible for the development of this disease. In the present
      review, we proposed a broadened concept of intrinsic and extrinsic factors for
      BPH. This concept offers identifiable research opportunities that will facilitate
      our quest in search for etiological agents for BPH. A brief description of
      various intrinsic and extrinsic factors and justifications for their selection
      will be discussed.

PMID- 9140128
TI  - Prostate cancer in African-American men.

PMID- 9140130
TI  - Evidence-based practice guidelines: a current perspective.

PMID- 9140129
TI  - Results of postoperative radiotherapy of cervix carcinoma after radical versus
      non radical hysterectomy.
AB  - We studied the outcome of our 68 cervix carcinoma patients treated either with:
      1) radical surgery and postoperative 192Ir high-dose rate afterloading
      brachytherapy or postoperative radiotherapy to the whole pelvis or with 2)
      standard hysterectomy and postoperative radiotherapy to the whole pelvis. Forty
      eight women were treated by radical hysterectomy from 1988 to 1992 and--due to
      risk factors--by postoperative radiotherapy (Group 1), 20 other patients (Group
      2) pretreated with standard hysterectomy were admitted to the university hospital
      for postoperative radiotherapy of the whole pelvis. Postoperative radiotherapy
      consisted of 39.6 Gy total dose using the box technique, plus two afterloading
      applications with a single dose of 7.5 Gy and 6 Gy external beam therapy to the
      pelvic lymph nodes sparing the midline. Comparing the Kaplan-Meier plots of both
      groups, the tumor related survival curve, the locoregional control and the rates
      of metastatic disease were nearly identical. But in the analysis of special
      subgroups, patients with positive lymph nodes after standard hysterectomy and
      postoperative radiotherapy had a worse prognosis (75% three years' survival rate)
      than patients after radical surgery (86% three years' survival rate).
      Lymphangiosis was a negative prognostic factor for the patients pretreated with
      standard hysterectomy (60% versus 80% three years' survival rate), but not for
      patients after radical surgery (80% three years' survival rate), despite the same
      radiotherapy in both groups. CONCLUSION: Standard hysterectomy fails to be an
      adequate treatment for early cervix carcinoma because moderately dosed
      postoperative radiotherapy cannot achieve complete locoregional control in all
      cases of positive lymph nodes or invasion of lymph vessels. However, based on the
      empirical results of many authors and our own results, postoperative radiotherapy
      is further indicated in high risk cases of cervix carcinoma after radical
      surgery.

PMID- 9140131
TI  - Worldwide prevention of vertical human immunodeficiency virus (HIV) transmission.
AB  - Most human immunodeficiency virus (HIV) infected children acquire the infection
      by perinatal transmission. Strategies for the prevention of perinatal HIV
      transmission mainly focus on conditions that prevail in industrialized countries,
      although most of these children are born in areas with less privileged
      circumstances. This review takes these circumstances into consideration when
      addressing six potential strategies to reduce perinatal HIV transmission.

PMID- 9140132
TI  - Clinical biological features of Ballantyne syndrome and the role of placental
      hydrops.
AB  - Ballantyne syndrome was first described in association with severe hydrops
      fetalis caused by rhesus isoimmunization, and lately, in association with diverse
      etiologies of nonimmunological severe fetal hydrops. This report is a case of
      typical Ballantyne syndrome in association with lethal hydrops fetalis caused by
      Ebstein's anomaly. It is likely that any severe fetal hydrops with massive
      placental hydrops may produce Ballantyne syndrome. Hemodilution could be the main
      biological feature, differentiating Ballantyne syndrome from usual preeclamptic
      syndromes. Pathophysiological hypotheses are discussed.

PMID- 9140133
TI  - Detection of human immunodeficiency virus type 1 and type 2 in the female genital
      tract: implications for the understanding of virus transmission.
AB  - Risk of perinatal or female to male sexual transmission of HIV is likely to be
      associated with whether, and at what concentration, the virus is present in the
      cervical and vaginal secretions of the HIV-infected woman. Examining correlates
      of cervical and vaginal HIV shedding is, therefore, essential for the development
      of strategies to interrupt HIV transmission. This article presents the rationale
      for using detection of HIV in the female genital tract as a marker of
      infectivity, and briefly describes methods for detecting HIV-1 and HIV-2 in
      cervical or vaginal fluids. Findings from studies incorporating the measurement
      of HIV in the female genital tract are reviewed, placing particular emphasis on
      issues relevant to epidemiological studies of HIV transmission.

PMID- 9140134
TI  - The potential role of iron chelators in the treatment of Parkinson's disease and
      related neurological disorders.
AB  - Neurodegeneration is characterized by a marked accumulation of iron in the
      affected brain regions. The reason for this is still unknown. In this article we
      review the available data on the possible involvement of iron and mediated
      oxidative stress in the aetiology of Parkinson's disease and related disorders.
      Iron chelators, if they effectively prevent radical formation, have great
      therapeutic potential against ischaemia/reperfusion, rheumatoid arthritis, and
      anthracycline toxicity, which are most likely free radical-mediated. The efficacy
      of the best established chelating drug desferal in neurodegenerative disease is
      limited due to its high cerebro- and oculotoxicity. New bioactive chelating
      agents are currently being developed, among them are oxidative stress activatable
      iron chelators which are most likely less toxic and can flexibly respond to an
      increase of free radical formation in the cell.

PMID- 9140135
TI  - Age might influence the frequency distribution of metoprolol hydroxylation
      polymorphism in a Chinese population.
AB  - The frequency distribution of the 8-hour urinary ratio of metoprolol/alpha
      hydroxymetoprolol (MR) was investigated in 206 healthy rural Chinese volunteers.
      The frequency of the poor metabolizer phenotype of metoprolol alpha-hydroxylation
      was 0% in this Chinese population. When the 206 subjects were subgrouped into
      four groups by age, the excretion of alpha-hydroxymetoprolol was significantly
      lower in the subjects with age older than 41 years compared to two younger groups
      (16-30 years), and the metoprolol hydroxylation metabolic ratio(metoprolol/a
      hydroxymetoprolol, MR) was higher in these middle-aged subjects, indicating that
      age may affect the frequency distribution of the 8-hour urinary MR or log MR,
      although multiple regression analysis did not show a significant correlation
      between age, urine volume and MR. Also, a significant correlation was found
      between age and the excretion (percentage of dose) of alpha-hydroxymetoprolol in
      8-hour urine (r = 0.259, P < 0.001). On the other hand, both multiple regression
      analysis and nonparametric tests showed that the larger the amount of urine
      excreted, the more metoprolol was recovered, demonstrating that the urinary
      excretion of unchanged metoprolol is renal flow-limited.

PMID- 9140136
TI  - Effects of ethanol on ethylmorphine metabolism in isolated rat hepatocytes:
      characterization by means of a multicompartmental model.
AB  - Hepatic cytochrome P-450 enzymes mediate at least two important biotransformation
      pathways of codeine and ethylmorphine starting with either N-demethylation or O
      dealkylation, producing polar metabolites which are then subsequently
      glucuronidated. The present study was designed to characterise the acute effects
      of ethanol on the metabolism of ethylmorphine and to compare it with the effects
      on codeine in suspensions of freshly isolated rat hepatocytes. Isolated rat
      hepatocytes from male Wistar rats were prepared by a collagenase perfusion
      method. Ethylmorphine, codeine and their metabolites were quantified by HPLC with
      UV detection. The total ethylmorphine elimination rate was reduced by 12% at 5mM
      and 38% at 100 mM ethanol. The corresponding percentages for codeine were 16 and
      43%. In the presence of ethanol the concentrations of several intermediate and
      end products of ethylmorphine and codeine changed markedly from the control
      situation. The experimental data were applied to a mathematical compartmental
      linear model to estimate the influence of ethanol on the separate reaction rates
      in the two main metabolic pathways. The ratios between reaction rate constants in
      the ethylmorphine experiments at 100 and 0 mM ethanol were 0.65 for ethylmorphine
      ->norethylmorphine, 0.63 for norethylmorphine-->normorphine, 0.56 for
      ethylmorphine-->morphine, 0.49 for morphine-->normorphine, 0.31 for normorphine-
      >normorphine-3-glucuronide and 0.49 for morphine-->morphine-3-glucuronide. Almost
      similar effects of ethanol on codeine metabolism were found. In additional
      experiments, norethylmorphine or norcodeine (50 microM) was incubated with 5 mM
      to 100 mM of ethanol and the metabolism of both norethylmorphine and norcodeine
      was found to be inhibited by ethanol in a concentration-dependent manner. The
      glucuronidation of morphine and normorphine added in separate experiments was
      also inhibited by ethanol, from 22 to 36% for morphine-3-glucuronide and 30 to
      60% for normorphine-3-glucuronide, respectively, in the presence of 5 mM to 100
      mM of ethanol. It was concluded that all steps in the metabolism of ethylmorphine
      (and codeine) leading to the end products morphine-3-glucuronide and normorphine
      3-glucuronide were inhibited by ethanol, and that the glucuronidation process
      were the ones most affected by ethanol.

PMID- 9140137
TI  - Comparative in vivo lead mobilization of meso- and rac-2,3-dimercaptosuccinic
      acids in albino Wistar rats.
AB  - Comparison of the racemic and meso forms of 2,3-dimercaptosuccinic acid (DMSA) in
      lead mobilization from lead-loaded albino Wistar rats demonstrates that the
      racemic form is significantly more effective in reducing femur lead levels. After
      four oral doses at 0.5 mmol/kg, femur lead levels were reduced to 87% of control
      values by meso-DMSA and to 50% of control levels by rac-DMSA. Similarly, when the
      dose was increased to 1.0 mmol/kg, femur lead levels were reduced to 69% of
      control levels by meso-DMSA and to 45% of control levels by rac-DMSA. A similar
      pattern was found for renal lead levels. Brain lead concentrations were
      significantly lower in treated groups than in control groups, but no differences
      were found between rac- and meso-DMSA. Rac-DMSA is more soluble than meso-DMSA in
      acetonitrile, ethyl acetate, and ethyl ether. The partition coefficient of rac
      DMSA in the n-octanol/water system was found to be about 2.8. These results
      indicate that rac-DMSA deserves further attention as a possible substitute for
      meso-DMSA.

PMID- 9140138
TI  - Elevated brain 5-hydroxytryptophol levels in experimental portal-systemic
      encephalopathy.
AB  - Brain tissue levels of the two serotonin metabolites 5-hydroxytryptophol and 5
      hydroxyindole-3-acetic acid (5-HIAA) were measured in porta-caval shunted rats,
      an in vivo model of portal-systemic encephalopathy. An intraperitoneal challenge
      of L-tryptophan (280 mg/kg body weight) to sham-operated rats was also instituted
      to increase the brain serotonin metabolism in these rats. The results revealed
      significant increases in 5-hydroxytryptophol (by 31% and 5-HIAA (by 87%) brain
      levels in porta-caval shunted rats as compared to sham-operated controls. The
      brain 5-hydroxytryptophol-to-5-HIAA ratio was lower in the porta-caval shunted
      rats. The 5-hydroxytryptophol levels in sham rats after the L-tryptophan
      challenge were intermediate between the porta-caval shunted and sham rats but not
      statistically significant for either group. These results suggest that increased
      brain 5-hydroxytryptophol levels might be associated with the pathogenesis of
      portal-systemic encephalopathy. Further, the elevated brain 5-hydroxytryptophol
      levels in experimental portal-systemic encephalopathy are probably a result of
      the increased brain serotonin metabolism prevailing in this condition rather than
      changes in the brain redox potential.

PMID- 9140139
TI  - Possible involvement of nitric oxide synthase in oxidative stress-induced
      endothelial cell injury.
AB  - The purpose of this study was to characterize the protective effect of NG-nitro-L
      arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, on
      oxidative stress-induced endothelial cell injury. Intracellular oxidative stress
      was induced by 1-chloro-2,4-dinitrobenzene, a glutathione (GSH) depleting agent,
      and the leakage of intracellular lactate dehydrogenase was measured as a marker
      of cell injury. Addition of 1-chloro-2,4-dinitrobenzene (100-500 microM) induced
      leakage of lactate dehydrogenase from endothelial cells, and the leakage of
      lactate dehydrogenase was strongly attenuated by L-NAME, but not by NG-methyl-L
      arginine, also an inhibitor of nitric oxide synthase. However, cell injury
      induced by the Ca2+ ionophore ionomycin was not affected by L-NAME or NG-methyl-L
      arginine. Moreover, neither L-NAME nor NG-methyl-L-arginine affected GSH
      depleting agent-induced or H2O2-induced cell injury in a rat foetal lung
      fibroblast cell line which lacks nitric oxide synthase. These results suggest
      that the protective effect of L-NAME is likely to be related to nitric oxide
      synthase, while the inhibition of nitric oxide production may not be involved in
      the protective effect of L-NAME, since NG-methyl-L-arginine did not affect
      endothelial cell injury.

PMID- 9140140
TI  - An affinity-modulating site on neuronal monoamine transport proteins.
AB  - The dissociation rates of [3H]nisoxetine, [3H]GBR 12935 and [3H]citalopram from,
      respectively, the rat brain noradrenaline, dopamine and 5-HT transporters were
      found to be markedly affected by several drugs. Sertraline strongly attenuated
      the rate of dissociation of [3H]nisoxetine from the noradrenaline transporter,
      while citalopram strongly attenuated that of [3H]citalopram from the 5-HT
      transporter. The effect of both drugs were stereospecific. Less potent affinity
      modulating drugs were identified with regards to [3H]GBR 12935 dissociation from
      the dopamine transporter. All three neuronal monoamine transporters may thus have
      specific affinity-modulating sites which change the function of the transporters
      with possible implication for the reuptake of monoamines released during synaptic
      activity.

PMID- 9140141
TI  - Oral vanadyl sulphate does not affect blood cells, viscosity or biochemistry in
      humans.
AB  - Vanadyl sulphate (VOSO4) is used to improve performance in weight training
      athletes. Concerns about its safety have arisen because vanadium compounds may
      cause anaemia and changes in the leukocyte system. In this study, the effects of
      oral VOSO4 (0.5 mg/kg/day) on haematological indices (red and white cell and
      platelet counts, red cell mean cell volume and haemoglobin level), blood
      viscosity (haematocrit, plasma viscosity and blood viscosity at 10s-1 and 100s-1
      shear rates) and biochemistry (lipids and indices of liver and kidney function)
      were investigated in a twelve week, double blind, placebo controlled trial in 31
      weight training athletes. Blood viscosity was evaluated at 0, 2, 4, 8 and 12
      weeks and haematological indices and biochemistry were measured before and at the
      end of treatment. Both the treatment group and placebo group showed increases in
      haematocrit (3.3-3.6%) and blood viscosity (9-11% at 100s-1 shear; 35-38% at 10s
      1 shear) but there were no significant effects of treatment. Similarly there were
      no treatment effects on haematological indices and biochemistry. Concerns about
      the adverse effects of oral vanadyl sulphate on blood are not supported by the
      results of this trial.

PMID- 9140142
TI  - Self-assessing supramolecular biovectors: a new dimension in novel drug delivery
      systems.

PMID- 9140143
TI  - Synthesis, stability and anticonvulsant activity of two new GABA prodrugs.
AB  - 4-(3,4-Dihydro-2,4-dioxo-2H-1,3-benzoxazin-3-yl)-butyric acid (7) and its ester
      6, two potential gamma-aminobutyric acid (GABA) prodrugs, were synthesized and
      studied to determine their stability in aqueous buffer and their susceptibility
      to undergo enzymatic hydrolysis in vitro (mouse plasma). Both compounds were
      fairly stable in aqueous media, (t1/2 = 68.2 h and 25.7 h, respectively). The 3,4
      dihydro-2,4-dioxo-2H-1,3-benzoxazine ring underwent enzymatic hydrolysis (t1/2 =
      5.8 h) in compound 7, whereas in compound 6 it seemed not to be opened by mouse
      plasma esterases within the observation time (3h). Both compounds were tested for
      their anticonvulsant activity in pentetrazole (PTZ) treated mice, and showed
      significant activity. Compound 7, administered as sodium salt 8, was active at
      relatively low doses and can be considered a very interesting GABA prodrug.

PMID- 9140145
TI  - Influencing virulence factors of Pseudomonas aeruginosa by commercially
      manufactured disinfectants.
AB  - Some commercially manufactured disinfectants tested (Desur, Dezox, Diesen forte,
      Lysoformin 3,000, Sokrena, Topax 91) depressed Pseudomonas aeruginosa virulence
      factors (elastase and proteinase), Nobacel did not. The degree of inhibition was
      directly proportional to the disinfectant concentration. The most effective
      concentrations were 1/4 of the MICs. Topax 91 most significantly suppressed
      proteinase activity (20.3%), Dezox was the most efficient in case of elastase
      (47.8%).

PMID- 9140146
TI  - Evidence of formation and participation of singlet oxygen in the in vitro
      phototoxicity of the combined diuretic triamterene and hydrochlorothiazide.

PMID- 9140147
TI  - Consequences of prolonged inhalation of ozone on F344/N rats: collaborative
      studies. Part XII: Atrophy of bone in nasal turbinates.
AB  - As part of the National Toxicology Program/Health Effects Institute collaborative
      study of the health effects of prolonged ozone exposure, it was observed that
      rats chronically exposed to ozone had marked histopathologic changes in the upper
      respiratory tract, including atrophy of the nasal turbinates. The principal
      objective of the present study was to morphometrically assess the severity of the
      ozone-induced changes in the bony tissue of the maxilloturbinates in these
      chronically exposed rats. Male and female F344/N rats were exposed to 0, 0.12,
      0.5, or 1.0 part per million (ppm) ozone, 6 hours/day, 5 days/week for 20 or 24
      months. Rats were killed one week after the end of the exposure, and nasal
      tissues were processed for light and electron microscopy. Using image analysis
      and standard morphometric techniques, the amounts of bone, surface epithelium,
      and lamina propria comprising the maxilloturbinates were estimated by measuring
      the cross-sectional area of each tissue compartment at a defined location in the
      proximal nasal passage. Both male and female rats had significant morphologic and
      morphometric changes in the maxilloturbinates after prolonged exposures to 0.5 or
      1.0 ppm ozone, but not to 0.12 ppm ozone. Ozone-exposed rats had significant
      reductions in the cross-sectional area of turbinate bone, reflecting the loss of
      bone in the maxilloturbinate after prolonged exposure. This ozone-induced bony
      atrophy was more severe in male than in female rats. Using electron microscopy,
      numerous bone-resorption sites were identified on the outer, periosteal, surface
      of the turbinate bone in ozone-exposed animals. Rats with bony atrophy also had a
      conspicuous influx and mixed inflammatory cells into the lamina propria
      surrounding the turbinate bone. In addition, ozone exposures caused reductions in
      the area of lamina propria, due to blood vessel constriction, and increases the
      in the area of the surface epithelium, due to hyperplasia and metaplasia. The
      results of the present tudy demonstrated that prolonged exposure of rats to ozone
      can cause marked loss of turbinate bone. The severity of this ozone-induced bony
      atrophy in rats is dependent on both concentration and gender.

PMID- 9140148
TI  - Short-bowel syndrome: an update on the therapeutic approach.

PMID- 9140150
TI  - Relation between histologic subtypes and location of gastric cancer and
      Helicobacter pylori.
AB  - BACKGROUND: Epidemiologic studies have consistently shown an association between
      Helicobacter pylori infection and gastric cancer, and it is now widely accepted
      that this organism plays a role in the pathogenesis of this tumor. Nevertheless,
      there are discrepant results on its relationship with the histologic type and
      location of gastric cancer within the stomach. The aim of this study was to
      determine the seroprevalence of H. pylori in a group of gastric cancer patients
      and the association between H. pylori and specific histologic types of gastric
      cancer and tumor location within the stomach. METHODS: Systemic IgG antibodies
      against H. pylori were assayed using an enzyme-linked immunosorbent assay
      technique in 48 patients (male to female ratio, 31:17; age range, 39-88 years;
      mean, 69 years) with histologically confirmed gastric cancer and 50 controls
      (male to female ratio, 33:17; age range, 40-77 years, mean, 64 years). RESULTS:
      Thirty-one cases of gastric cancer were of the intestinal type, and 12 of the
      diffuse type; the remaining 5 were unclassified. Thirteen gastric cancers were
      located in the distal stomach (antrum/pylorus), 12 in the body, and 5 in the
      proximal stomach (cardia/fundus); the remaining 17 were unclassified because the
      tumor extended towards more than one location. The overall seroprevalence of H.
      pylori in patients with gastric cancer and controls was 85.4% and 66%,
      respectively (P < 0.05). The seroprevalence increased with increasing age in
      cancer patients, but the difference was not significant. H. pylori seroprevalence
      among patients with the intestinal type of gastric cancer was higher than in
      those with the diffuse type (P < 0.05). The prevalence of H. pylori infection was
      higher among patients with the cancer located distally than in those with the
      cancer located proximally (P < 0.05). CONCLUSIONS: H. pylori seroprevalence was
      higher in gastric cancer patients than in controls. The prevalence of H. pylori
      infection in intestinal-type gastric cancer was clearly higher than in the
      diffuse type and in the control group. An association was found between H. pylori
      infection and tumors located distally (antrum/pylorus).

PMID- 9140149
TI  - Evaluation of experimental therapeutics in a new mouse model of Helicobacter
      felis utilizing 16S rRNA polymerase chain reaction for detection.
AB  - BACKGROUND: A new mouse model of Helicobacter felis infection, which mimics the
      human infection observed with H. pylori, has recently been developed utilizing
      polymerase chain reaction (PCR) based on the 16S rRNA gene sequence for detection
      of infection. METHODS: We tested several therapeutic regimens in this model,
      including some currently utilized in the clinic and some shown ineffective in the
      clinic. RESULTS: The therapeutic results obtained by PCR with this model are
      consistent with results observed in the published human H. pylori clinical trials
      and also with results obtained in another H. felis mouse model utilizing culture
      and histology. CONCLUSIONS: These results support further use of this new model
      in screening for new therapeutic regimens for the management of Helicobacter
      disease.

PMID- 9140151
TI  - 13C-urea breath test in Helicobacter pylori diagnosis and eradication.
      Correlation to histology, origin of 'false' results, and influence of food
      intake.
AB  - BACKGROUND: Which protocol is optimal for the 13C-urea breath test (UBT) for
      Helicobacter pylori detection is controversial. This study aimed to characterize
      a very simple UBT protocol for the clinical routine (two-point-analysis performed
      with 75 mg 13C-urea and citric acid) with special consideration of 'false' UBT
      results. RESULTS; UBT was evaluated in reference to histology (Warthin-Starry).
      In mismatching results re-gastroscopy was performed. By UBT, 74 of 77 patients
      with H. pylori-positive histology were detected (sensitivity, 96%). The false
      negative UBTs were due to low colonization densities during spontaneous H. pylori
      elimination or pyloric obstruction. Seven of 49 patients with negative histology
      had a positive UBT, but re-gastroscopy showed that all of them had a positive
      histology when multiple antral biopsy specimens were taken (UBT specificity,
      100%). UBT correlated only weakly with H. pylori colonization density. No
      correlation was found between UBT and gastric neutrophil and lymphocyte
      infiltration. UBT reproducibility was excellent (93 of 94 in a 6-month period).
      Non-fasting conditions induced a shift to lower UBT results in H. pylori-positive
      and to higher UBT results in negative patients, resulting in 2 of 10 false
      positive and 1 of 10 false-negative UBTs. CONCLUSION: This simple version of the
      urea breath test combines the highest sensitivity with excellent reproducibility.
      It is superior to histologic detection of H. pylori in the clinical routine and
      an optimal tool for monitoring H. pylori eradication. Fasting conditions are
      required for the test.

PMID- 9140152
TI  - Plasma concentrations of cholecystokinin and neurotensin in patients with cystic
      fibrosis.
AB  - BACKGROUND: Regulation of pancreatic exocrine secretion is controlled by
      vagovagal reflexes and hormones. A negative feedback control mechanism exists
      between the intraduodenal protease concentration and pancreatic enzyme secretion.
      In man cholecystokinin (CCK) is the major regulator of postprandial pancreatic
      enzyme secretion. There is a 50% reduction of meal-stimulated secretion by the
      specific CCK receptor antagonist loxiglumide, whereas atropine completely blocks
      postprandial secretion. Neurotensin is released postprandially by nerval reflexes
      and fat. It has been claimed that both hormones are increased in patients with
      pancreatic insufficiency. METHODS: We investigated CCK and neurotensin levels in
      patients with cystic fibrosis and pancreatic insufficiency. In 35 patients (2-24
      years old) with cystic fibrosis with steatorrhea and in 15 patients (1.5-24 years
      old) with cystic fibrosis without pancreatic insufficiency pre- and post-prandial
      CCK and neurotensin plasma levels were measured 3 days after pancreatic enzyme
      therapy had been withdrawn. Nine patients (3-14 years old) who had no complaint
      of abdominal disease served as controls. RESULTS: Basal and postprandial CCK
      plasma levels did not differ statistically in the three groups, whereas basal and
      postprandial neurotensin levels were significantly increased in the cystic
      fibrosis groups. The severity of the disease had no effect on the neurotensin
      levels. CONCLUSIONS: Cystic fibrosis patients with severe pancreatic
      insufficiency did not have increased CCK plasma levels, suggesting that a CCK
      mediated feedback mechanism of pancreatic enzyme secretion does not operate in
      our patients. In contrast, basal and postprandial neurotensin plasma levels were
      significantly increased in patients with cystic fibrosis but were independent of
      the severity of the pancreatic insufficiency.

PMID- 9140153
TI  - Effect of omeprazole on the outcome of endoscopically treated bleeding peptic
      ulcers. Randomized double-blind placebo-controlled multicentre study.
AB  - BACKGROUND: Haemostasis is highly pH-dependent and severely impaired at low pH.
      However, there is no clear evidence that acid-suppressing drugs have beneficial
      effects in peptic ulcer haemorrhage. Endoscopic haemostatic treatment provides
      important reduction in morbidity and may be more efficient when a neutral
      intragastric pH is maintained. METHODS: We conducted a double-blind, placebo
      controlled multicentre study of intravenous infusion of omeprazole (80 mg as
      bolus, followed by 8 mg/h) or placebo for 72 h. All patients received 20 mg
      omeprazole orally from day 3 until follow-up on day 21. Only patients with ulcer
      haemorrhage, endoscoped within 12 h after admission, and with a history or signs
      of circulatory failure and spurting bleeding, oozing bleeding, visible vessel, or
      clot, were included. Endoscopic intervention was aimed at when spurting bleeding,
      oozing bleeding, or a visible vessel was observed. The primary efficacy measure
      was the worst ranking on an overall outcome scale (5 = death, 4 = surgery, 3 =
      additional endoscopic treatment, 2 = more than 3 units of blood, and 1 = no more
      than 3 units of blood transfused). Base-line prognostic factors of treatment
      success by day 3 and of other binary outcomes were considered in a logistic
      regression model. RESULTS: Two hundred and seventy-four patients were randomly
      assigned to omeprazole (134 patients) or placebo (140 patients). The number of
      patients included in the 'intention-to-treat' analysis was 130 in the omeprazole
      group and 135 in the placebo group. The primary variable, the overall outcome at
      72 h, showed a difference (P = 0.004) between the two treatments in favour of
      omeprazole. Treatment success by 72 h defined as no death, no operation, or no
      additional endoscopic treatment was 91.0% in the omeprazole group and 79.7% in
      the placebo group (therapeutic gain, 11.3 percentage units; 95% confidence
      interval, 2.3 to 20.4 percentage units). Significant differences in favour of
      omeprazole were also found for secondary variables such as number of blood
      transfusions, duration and degree of bleeding, and the need for surgery and
      additional endoscopic treatments on day 3 and day 21. However, the numbers of
      deaths by day 3, 21, or 35 were very similar. CONCLUSIONS: We found a beneficial
      effect of intravenous omeprazole in severe ulcer haemorrhage, with a reduction in
      the number of operations, in endoscopic treatments, and in the duration and
      severity of bleeding.

PMID- 9140154
TI  - Continuous intravenous infusion of omeprazole in elderly patients with peptic
      ulcer bleeding. Results of a placebo-controlled multicenter study.
AB  - BACKGROUND: Does profound acid inhibition by continuous infusion of omeprazole
      for 72 h reduce further bleeding in elderly patients with peptic ulcer bleeding
      (PUB)? METHODS: Three hundred and thirty-three patients > or = 60 years old with
      PUB were randomized to omeprazole (80 mg + mg/h) or placebo as continuous
      infusion for 72 h. From day 4 to 21 all patients received 20 mg omeprazole orally
      once daily. RESULTS: When evaluated on day 3, the primary variable 'overall
      outcome' (based on an ordinal ranking scale; see Study variables) (P = 0.017) and
      the secondary variables, surgery (P = 0.003), degree (P = 0.004) and duration of
      bleeding (P = 0.003) all favored the omeprazole group. Blood transfusions, need
      for endoscopic treatment, and mortality were not statistically different. On
      follow-up, by day 21, the mortality in the group initially receiving intravenous
      omeprazole was 6.9%, while the intravenous placebo group showed an extremely low
      mortality, 0.6%. CONCLUSION: Three days' infusion of omeprazole improved overall
      outcome and reduced need for intervention in PUB patients.

PMID- 9140155
TI  - A review of 20 years of jejunoileal bypass.
AB  - BACKGROUND: The long-term effects of jejunoileostomy for morbid obesity were
      studied 15-20 years after surgery, in 60 patients. METHODS: A total of 141
      patients underwent surgery during the years 1973 to 1979. Thirty-four (24%) had
      had bowel continuity reestablished because of side effects. Eight (5.6%) were
      dead, 4 (2.8%) had emigrated, and 11 (7.8%) lived in remote areas, leaving 84
      patients for follow-up. Sixty of these patients agreed to participate in the
      study. Seventy-seven per cent of the study population were women, with a mean age
      of 50 years. RESULTS: The average weight loss was 50.2 kg; only one patient had
      regained the preoperative weight. The average weight was 84.2 kg. Reported side
      effects were 1) gastrointestinal: diarrhoea (61.7%), bad defecation smells (60%),
      and meteorism (11.7%), and 2) systemic: arthralgia (18.3%) and symptomatic
      nephro/cholelithiasis (18.3%). Forty-two patients (70% of the participants) found
      the results acceptable/satisfactory. Nine patients (15%) had vitamin B12
      injections regularly; another 22 (35%) were found to have a low cobalamin level,
      and 35 patients (58%) had reduced P-magnesium. The 25-hydroxycholecalciferol
      level was low in 26 patients (43%), parathyroid hormone values were increased in
      18 (30%). Fifty-seven patients (95%) had a P-carotene value lower than the normal
      limit. CONCLUSION: These results stress the need for continuous control and
      supplementary therapy.

PMID- 9140156
TI  - Variations in pigment and carbohydrate content of gallbladder bile affect
      accurate quantitation of total protein when using the fluorescamine method.
AB  - BACKGROUND: Despite solute dilution and reduced total lipid concentrations, an
      unexplained increase in protein concentration has been reported to occur in the
      gallbladder bile of cholesterol gallstone patients. METHODS: Solutes in
      gallbladder bile from gallstone-free controls and from four study groups were
      measured using standard methods. Total proteins were measured using amino acid
      analysis and a conventional fluorescamine method. RESULTS: Bile salts and pigment
      content were greater in gallstone-free controls than in all other study groups,
      including morbidly obese gallstone-free subjects. Total biliary protein
      concentration, as determined by amino acid analysis in the gallstone-free control
      group was higher than in non-obese gallstone patients with multiple stones and in
      morbidly obese gallstone-free subjects. Total biliary proteins as measured with
      fluorescamine, however, did not show intergroup differences. A major problem of
      the conventional fluorescamine assay is shown to be an artefact arising from the
      high pigment content of the more concentrated samples. CONCLUSIONS: Very dilute
      gallbladder bile samples are often found in the presence of gallstone disease.
      This also occurs in morbidly obese subjects, even in the absence of gallstones.
      Although the contribution of protein secretion/absorption by the gallbladder can
      also be relevant, especially in the presence of morbid obesity, the protein
      concentration in gallbladder bile, when accurately measured, generally parallels
      the concentrations of non-absorbed biliary solutes, reflecting the efficiency of
      fluid absorption. Measurement of biliary proteins by the conventional
      fluorescamine method is unreliable in clinical studies in which intergroup
      differences in pigment content are commonly present.

PMID- 9140157
TI  - Steatosis and collagen content in experimental liver cirrhosis are affected by
      dietary monounsaturated and polyunsaturated fatty acids.
AB  - BACKGROUND AND METHODS: We used thioacetamide administered orally to induce
      cirrhosis in rats, and after these had recovered for 1 and 2 weeks we examined
      the effects of dietary supplementation with monounsaturated and n-3
      polyunsaturated fatty acids, or with a combination of n-3 and n-6 polyunsaturated
      fatty acids, on the extent of steatosis and collagen content in the liver.
      RESULTS: Nodular cirrhosis, increased collagen content, and lipid accumulation
      were established after 4 months of treatment with thioacetamide. When the animals
      were fed a diet rich in oleic acid for 2 weeks, the steatosis and fibrosis
      decreased. Supplementation with n-3 polyunsaturated fatty acids favored
      reductions in collagen content but did not reduce the fat accumulation. With a
      diet supplemented with a mixture of n-3 and n-6 fatty acids we found no reduction
      in either lipid accumulation or collagen content. CONCLUSIONS: Fibrosis and
      steatosis may be influenced by dietary fat, and monounsaturated fat appears to
      influence favorably the histologic recovery of the damaged liver.

PMID- 9140158
TI  - Plasma carnitine kinetics during orthotopic liver transplantation.
AB  - BACKGROUND: Carnitine is synthesized mainly in the liver and plays an essential
      role in the transport of fatty acids in liver mitochondria for subsequent
      oxidation and energy production. METHODS: The plasma concentrations of free
      carnitine, acylcarnitine, total ketone bodies, lactate, pyruvate, and hepatocyte
      growth factor (HGF) were measured during liver transplantation. RESULTS: The
      plasma free carnitine and acylcarnitine concentrations and the lactate to
      pyruvate ratio in patients with compromised grafts (group A) were significantly
      higher than those in patients with well-functioning grafts (group B) after
      reperfusion. The acylcarnitine concentration in group B decreased after incision,
      but it remained at a high level in group A. Significant correlations were found
      between the concentrations of HGF and free and acylcarnitine after reperfusion.
      CONCLUSION: The accelerated flux of carnitine in the graft may be associated with
      deterioration of energy metabolism in the graft. An increased acylcarnitine
      concentration may reflect impaired liver regeneration.

PMID- 9140159
TI  - Forceps biopsy and brush cytology during endoscopic retrograde
      cholangiopancreatography for the diagnosis of biliary stenoses.
AB  - BACKGROUND: For evaluating pancreaticobiliary stenoses during endoscopic
      retrograde cholangiopancreatography (ERCP) tissue sampling techniques may be
      important. Brush cytology and forceps biopsy during ERCP are two potential, but
      so far only incompletely evaluated, tools for the diagnosis of malignant biliary
      or pancreatic stenoses. METHODS: Between 1992 and 1995 we acquired 133 cytologic
      and/or histologic samples from 119 patients who underwent ERCP because of biliary
      duct stenoses. Sixteen patients had to be excluded from the study due to
      insufficient follow-up information. After papillotomy, brush cytology was
      performed in 65 cases (63 patients), and forceps biopsy in 119 cases (106
      patients under fluoroscopic guidance. Both methods were applied in combination 51
      times (48 patients). The nature of the stenoses was confirmed by surgery,
      autopsy, or by the subsequent clinical course. RESULTS: The sensitivity was 46.7%
      for brush cytology and 64.9% for forceps biopsy. The combined application of both
      methods resulted in superior sensitivity (70.4%). Specificity was 100% for all
      methods. CONCLUSIONS: These numbers lead us to recommend a combined and more
      frequent application of brush cytology and forceps biopsy of bile duct stenoses
      to enhance the diagnostic yield whenever substantial influence on therapy can be
      expected.

PMID- 9140160
TI  - Low-dose versus high-dose ursodeoxycholic acid in cystic fibrosis-related
      cholestatic liver disease. Results of a randomized study with 1-year follow-up.
AB  - BACKGROUND: Ursodeoxycholic acid (UDCA) is beneficial in cholestasis related to
      cystic fibrosis (CF). High-dose treatment has been recommended to compensate for
      bile salt malabsorption. We compared the results of low-dose (10 mg/kg/day) and
      high-dose (20 mg/kg/day) UDCA treatment on liver biochemistry after 3 and 12
      months' treatment. METHODS: Thirty CF patients (age > 5 years) with biochemical
      cholestasis and compensated liver disease were randomized for low-dose (n = 17)
      or high-dose (n = 13) UDCA. Baseline clinical variables were comparable. RESULTS:
      After 1 year one patient had died of liver failure (low dose), and three had
      dropped out because of pruritus (one in each group) or personal choice (low
      dose). In the high-dose group improvement in gamma-glutamyl transferase values
      was more pronounced after 3 months and 1 year (P < 0.004), and improvement of
      alanine aminotransferase was better after 1 yer (P < 0.02). Improvement of
      alkaline phosphatase and aspartate aminotransferase was comparable. Complete
      normalization of liver enzymes and bilirubin occurred more often in the high-dose
      group. CONCLUSION: High-dose UDCA induces a better response of liver biochemistry
      values than low-dose UDCA in CF patients with cholestatic liver disease.

PMID- 9140161
TI  - Feedback regulation of pancreatic exocrine secretion in minipigs.
AB  - BACKGROUND: The mechanism behind the possible feedback regulation of pancreatic
      exocrine secretion is not well understood. METHODS: Thirteen minipigs were
      prepared with fistulas to the pancreatic duct and the duodenum. Peripheral venous
      blood was obtained for determination of secretin and cholecystokinin (CCK)
      levels. Four different experiments were performed: 1) diversion and reinfusion of
      pancreatic juice; 2) intraduodenal infusion of NaHCO3 solution, with the same
      volume, bicarbonate concentration, and osmolality as the collected pancreatic
      secretion, and reinfusion of pancreatic juice; 3) reinfusion of pancreatic
      secretion for 1 h before and 2 h after a meal; and 4) diversion of pancreatic
      secretion and intraduodenal infusion of NaHCO33 solutions before and after a
      meal. RESULTS: Reinfusing pancreatic juice significantly decreased pancreatic
      juice volume and bicarbonate output and slightly decreased the level of secretin
      in plasma. Alternating infusions of substitute NaHCO3 and pancreatic juice did
      not change pancreatic output of bicarbonate and protein, nor did it change the
      CCK and secretin levels in plasma. Replacing pancreatic juice with intraduodenal
      NaHCO3 infusions during a meal did not significantly modify the pancreatic
      secretion of bicarbonate and protein or the hormonal levels in blood.
      CONCLUSIONS: A negative feedback regulation of pancreatic exocrine secretion is
      present in starved minipigs. Duodenal acidity and plasma levels of secretin semm
      to be of importance, whereas duodenal enzyme activity and the level of CCK in
      plasma probably are not. A postprandial negative feedback regulation through
      duodenal enzymatic activity and release of CCK into blood could not be shown.

PMID- 9140162
TI  - Total parenteral nutrition affects the tropic effect of cholecystokinin on the
      exocrine pancreas.
AB  - BACKGROUND: Cholecystokinin (CCK) exerts trophic effects on the exocrine
      pancreas. Total parenteral nutrition (TPN) results in hypotrophy of the pancreas.
      The present study aimed to examine the effect of exogenous and endogenous CCK
      during TPN. METHODS: Seventy-two Sprague-Dawley rats were orally fed or given TPN
      after pancreaticobiliary diversion (PBD) and were infused with CCK-8S or the CCK
      receptor antagonist devazepide for 7 days. RESULTS: Infusion of CCK and PBD
      caused hyperCCKemia, whereas TPN did not influence the concentration of plasma
      CCK. The reduced pancreatic contents during TPN could be reversed by CCK but not
      by PBD. The hyperplastic response to CCK in orally fed rats was abolished during
      TPN. Devazepide did not influence the pancreatic variables in orally fed and TPN
      treated rats. CONCLUSION: TPN reduces the hyperplastic response of the exocrine
      pancreas to CCK, and CCK reverses the hypotrophy seen during TPN. The effects of
      CCK on the exocrine pancreas seems to need enteral nutrition for the full
      expression.

PMID- 9140163
TI  - Detection of antibodies to hepatitis E virus in patients with autoimmune chronic
      active hepatitis and primary biliary cirrhosis.
AB  - BACKGROUND: Viral hepatitis E (HIV) frequently causes epidemic outbreaks in many
      developing countries. It is also present in developed countries as imported
      cases. The role of hepatitis A virus as trigger for autoimmune chronic hepatitis
      has been demonstrated, and it has been suggested that this may also apply to HEV.
      METHODS: The presence of anti-HEV antibodies in serum samples from patients with
      autoimmune chronic active hepatitis (n = 52) and with primary biliary cirrhosis
      (n = 25) was investigated using an Abbott assay and a peptide-based test.
      RESULTS: Anti-HEV antibodies were detected with the Abbott test in 13% (7 of 52)
      of the patients with autoimmune chronic active hepatitis, but not of these were
      positive in the synthetic peptide-based test. CONCLUSION: These findings indicate
      the HEV is not associated with primary biliary cirrhosis but may be implicated in
      some cases of autoimmune chronic active hepatitis.

PMID- 9140164
TI  - Liver reactions to oral low-dose tetracyclines.
AB  - BACKGROUND: We report on a case of severe liver reaction associated with
      doxycycline in a previously healthy subject. Furthermore, we estimate the
      incidence of oral low-dose tetracycline-related liver reactions in relation to
      sales figures in Sweden and study the clinical and biochemical features of low
      dose tetracycline-associated liver injury, on the basis of reports to SADRAC
      (Swedish Adverse Drug Reactions Advisory Committee) and on the reports in the
      literature. METHODS: All liver reactions reported to SADRAC from 1965 to 1995
      were surveyed, and articles on liver reactions resulting from tetracycline
      published during the period 1966-95 were reviewed. RESULTS: During this 30-year
      period, 23 liver reactions with a suspected casual relationship to oral, low-dose
      tetracycline derivatives were reported to SADRAC. A causal relationship was
      considered likely in 3 and possible in 8 cases, giving an incidence of roughly 1
      in 18 million DDD (defined daily doses). No deaths were observed from these liver
      reactions, and liver enzyme activities normalized in all cases without any
      serious clinical consequences. A total of three cases of reported tetracycline
      liver damage were found in the literature. Of these, two were classified as
      having a likely relationship, and in one a causal relationship was not
      determinable because of other concomitant drug administration. The liver injury
      was designated as cholestatic, hepatocellular, and mixed, with similar
      frequencies. CONCLUSIONS: Low-dose, oral tetracyclines constitute a likely cause
      of acute liver damage with a variable biochemical profile. Such reactions are
      probably very rare.

PMID- 9140165
TI  - Does profound acid inhibition improve haemostasis in peptic ulcer bleeding?

PMID- 9140166
TI  - Pathogenic properties of Helicobacter pylori.

PMID- 9140167
TI  - Familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal
      cancer (HNPCC): a review of clinical, genetic and therapeutic aspects.
AB  - Familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal
      cancer (HNPCC) are two syndromes of colorectal cancer predisposition, inherited
      in an autosomal dominant fashion. They account for about 1% and 5-7% of all
      colorectal cancer cases, respectively. FAP is caused by germline mutations of a
      tumour suppressor gene, the adenomatous polyposis coli (APC) gene, whereas HNPCC
      results from genetic alterations of the DNA mismatch repair genes. Clinical
      manifestations in FAP include colonic as well as extracolonic sites (duodenum,
      eye, dental, nervous or connective tissues). In FAP, prophylactic colectomy is
      required in all affected patients and regular endoscopic check-up of the upper
      gastrointestinal tract is necessary to detect malignant transformation of
      duodenal polyps; medical management of complex desmoid tumours is preferred
      rather than surgery. In HNPCC, there are extracolonic associated endometrial,
      gastric, small bowel or brain carcinomas. At present time, for HNPCC patients,
      only preventive measures such as regular colonoscopic or gynecologic examinations
      are recommended, since prophylactic colectomy or hysterectomy are not considered
      to be routine procedures.

PMID- 9140168
TI  - The use of allogeneic leukocytes or i.v. IgG for the treatment of patients with
      recurrent spontaneous abortions.

PMID- 9140169
TI  - The thrombocytopenic rabbit bleeding time model to evaluate the in vivo
      hemostatic efficacy of platelets and platelet substitutes.

PMID- 9140170
TI  - In vitro assessment of platelet function.
AB  - With the realization that the skin bleeding time is often an unreliable measure
      of platelet function, efforts have been made to identify ways to assess
      qualitative platelet dysfunction. Currently available techniques measure platelet
      adhesion, platelet aggregation, the ability of platelets to retard or stop flow
      through fibers, and the contribution of platelets to in vitro clot formation.
      Glass bead adhesion, which continues to be performed in some laboratories, is
      gradually being replaced by measures of platelet adhesion to filters composed of
      glass fibers, Dacron fibers, or collagen. In each instance, anticoagulated
      platelet-rich plasma or whole blood flows through the filter under a regulated
      pressure gradient. The amount of blood flowing through the filter versus time
      and/or the time to filter occlusion are measured. Recent developments in platelet
      aggregation have focused on whole blood and stagnation point flow aggregation
      techniques. Whole blood aggregation does not require blood sample processing and
      accommodates blood obtained from citrated vacutainer tubes. Stagnation point flow
      measures both platelet adhesion and aggregation and may be able to detect
      pathologically-enhanced platelet function. Global measures of hemostasis attempt
      to simultaneously evaluate the adequacy of fluid phase coagulation and platelet
      function. Currently available techniques include Thromboelastography, SonoClot
      Analyzer, Hemodyne Hemostasis Analyzer, PITT, and Hemostatometry. Although each
      of these technologies have been shown to provide interesting data in the research
      setting, the ability of any of these techniques to detect abnormal or clinical
      inadequate platelet function remains to be established.

PMID- 9140171
TI  - A comparative analysis of different methods for routine blood component
      preparation.

PMID- 9140172
TI  - The platelet storage lesion.

PMID- 9140173
TI  - Variation of common carotid artery elasticity with intimal-medial thickness: the
      ARIC Study. Atherosclerosis Risk in Communities.
AB  - The Atherosclerosis Risk in Communities (ARIC) study is a prospective
      investigation of the etiology and natural history of atherosclerosis and
      cardiovascular disease in four U.S. communities. The purpose of this work is to
      investigate the relationship between common carotid artery elasticity and intimal
      medial thickness (IMT) in the four race-gender groups represented in the ARIC
      cohort. Noninvasive ultrasonic methods were used to measure IMT and the [systolic
      minus diastolic] diameter change (DC) of the left common carotid artery in 10,920
      black and white, men and women between the ages of 45 and 64 y. The relationship
      between DC and IMT and IMT2 was examined after adjustment of DC for age, height,
      diastolic diameter, diastolic blood pressure and linear and quadratic terms for
      pulse pressure. This adjusted value of DC was used as an index of elasticity of
      the common carotid artery in the ARIC cohort with larger values of adjusted DC
      implying a more elastic vessel. The general behavior of adjusted DC with
      increasing IMT was observed to be qualitatively similar in all four race-gender
      groups. Adjusted DC remained nearly constant or increased slightly for values of
      IMT between approximately 0.4 and 0.8 mm, up to approximately the 90th percentile
      of IMT, and then decreased above the 90th percentile of IMT. Common carotid
      artery elasticity, defined as adjusted DC, varies with increasing IMT in the ARIC
      cohort in a manner consistent with results from previous studies in animals and
      human subjects addressing the variation of several elasticity indices with
      atherosclerotic involvement and risk factor exposure in the aorta, and brachial
      and radial arteries. Our results suggest that thicker common carotid artery walls
      in middle-aged U.S. populations are no stiffer than thinner walls, except for the
      thickest 10% of arteries. Since the distal common carotid artery frequently
      contains atheromatous plaques in this population, the lack of change in
      stiffness, indeed, the reduction in stiffness per unit thickness, may reflect the
      various stages of early common carotid atherosclerosis most often found in this
      population. These are characterized more by destruction of arterial wall
      structural elements than by changes such as widespread or circumferential
      sclerosis, which would strengthen and stiffen the artery.

PMID- 9140174
TI  - Lack of correlation between ultrasonography and histologic staging of the
      endometrium in in vitro fertilization (IVF) patients.
AB  - In 53 patients of an in vitro fertilization (IVF) program with unsuccessful
      fertilization of oocytes, an endometrial biopsy was carried out on the day of the
      intended embryo transfer. The results were compared with the thickness (assessed
      on the very same day by means of ultrasonography) and the echo pattern of the
      endometrium, which was classified into four grades (A to D). We found grade A in
      16 cases (30%), grade B in 22 cases (41.5%) and grade C in 15 cases (28.5%); no
      endometrium was assessed as grade D. The distribution of histologic findings was
      not significantly skewed within the respective grading categories (only 37.5% of
      grade A endometria, 63.5% of grade B endometria and 66.5% of grade C endometria
      were in phase with the menses). The in-phase and out-of-phase endometria did not
      display significant differences in endometrial thickness (8.8 +/- 0.29 mm vs.
      9.13 +/- 0.4mm). Neither the sonographically measured endometrial thickness nor
      the echo pattern correlated with the histologic findings, suggesting that
      ultrasonography is inadequate for drawing reliable conclusions about endometrial
      receptivity in an IVF program.

PMID- 9140175
TI  - Ductus venosus revisited: a Doppler blood flow evaluation in the first trimester
      of pregnancy.
AB  - The functional role of the fetal ductus venosus (DV) is still poorly established.
      Few reports are available in the literature concerning assessment of fetal venous
      return during the late first trimester of pregnancy. Our objective was to
      determine the normal Doppler blood velocity waveform in the human fetal DV as
      early as 10-13 weeks gestation. Adopting strict methodological concerns, 61
      Doppler blood flow evaluations of the DV considered technically acceptable were
      selected. Using transvaginal Doppler ultrasound, several DV haemodynamic
      parameters were assessed: peak systolic and diastolic velocities, time-averaged
      velocity, maximum velocity during atrial contraction, pulsatility index and fetal
      heart rate (FHR). Except for the FHR, no significant variations were observed for
      the above mentioned parameters during this period, and no correlation could be
      established between FHR and the different flow velocity parameters. Further
      knowledge about DV haemodynamics in the early phases of pregnancy may make a
      valuable contribution to the understanding of fetal venus return to the heart and
      cardiac function.

PMID- 9140176
TI  - Effects of velocity distribution, diameter measurement and velocity tracing on
      the accuracy of cardiac output measurement by pulsed Doppler echocardiography in
      the aortic annulus of pigs.
AB  - The accuracy of cardiac output measurement by pulsed Doppler echocardiography can
      be affected by several factors, such as the velocity distribution, the
      measurement of diameter and the method of tracing the pulsed Doppler flow
      spectrum. This experimental study was designed to find the most accurate way of
      measuring cardiac output in consideration of all these factors. In 10 open-chest
      normal piglets (24 +/- 1 kg), the velocity distribution in the aortic annulus was
      evaluated using Doppler colour flow mapping. Cardiac output was measured by
      pulsed Doppler echocardiography in the aortic annulus by a number of different
      ways and compared to the simultaneous result of the thermodilution method. All
      measurements were made at baseline, after intravenous injection of esmolol and
      during infusion of dobutamine. RESULTS: (1) the velocity distribution in the
      aortic annulus in the piglets was just slightly skewed during all three
      haemodynamic situations; (2) The in vivo measurements of the diameter of the
      aortic annulus varied throughout the ejection period, but the average of the
      three largest diameter measurements was almost identical with the diameter
      measured in vitro (18.5 +/- 0.3 mm vs. 18.6 +/- 0.2 mm; p = NS); (3) Tracing the
      maximal velocity of the pulsed Doppler flow spectrum produced a cardiac output
      that was 18%-21% higher than that measured by the thermodilution method, while
      tracing the brightest part (modal velocity) of the pulsed Doppler flow spectrum
      yielded a cardiac output very close to the thermodilution measurement.
      CONCLUSION: The velocity distribution in the aortic annulus in the piglet has
      little effect on cardiac output measurement by pulsed Doppler. Using the maximal
      measurable diameter of the aortic annulus and tracing the brightest part of the
      pulsed Doppler flow spectrum yielded the cardiac output closest to that measured
      by the thermodilution method.

PMID- 9140177
TI  - Assessment of mitral A-wave transit time to cardiac outflow tract and isovolumic
      relaxation time of left ventricle in the appropriate and small-for-gestational
      age human fetus.
AB  - Mitral A-wave transit time (Ta; ms) from the mitral valve to the left ventricular
      outflow tract and left ventricular isovolumic relaxation time (IRT) were studied
      by pulsed Doppler ultrasound in 17 appropriate-for-gestational-age fetuses (AGA,
      30-39 wk) and 12 small-for-gestational-age fetuses (SGA, 30-36 wk). Ta was
      measured from the peak of the A-wave to the peak of the reflected A-wave (Ar)
      from the left ventricular wall. IRT was determined from the interval between the
      aortic valve closure artefact and the onset of transmitral flow. The mean Ta in
      the SGA fetus (42 +/- 7 [1 SD] ms) was significantly shorter (p < 0.03) than in
      the AGA fetus (47 +/- 11 [1 SD] ms), whereas this was not so for IRT (51 +/- 8 [1
      SD] ms vs. 60 +/- 15 [1 SD] ms). In the SGA fetus, a positive correlation (r =
      +0.82, p < 0.01) was established between Ta (ms) and gestational age. No such
      correlation existed for the AGA fetus. It is speculated that, in the SGA fetus,
      the shorter Ta may reflect an increase in left ventricular stiffness.

PMID- 9140178
TI  - Characterisation of atherosclerotic plaque by spectral analysis of intravascular
      ultrasound: an in vitro methodology.
AB  - Raw 30-MHz intravascular ultrasound data have been captured from postmortem
      coronary arteries (n = 4) to develop radio frequency analysis techniques for the
      characterisation of atherosclerotic plaque. Digitised data acquired from
      positions (n = 8) within diseased sections of artery were compared with the
      corresponding histology and radiology. Scan-converted images were used to locate
      regions of interest (ROI = 33) within areas of tissue composition: loose fibrotic
      tissue (LFT), dense fibrotic tissue (DFT) and calcium (CA). A range of parameters
      was extracted from the normalised power spectrum of each ROI within the bandwidth
      17-42 MHz. Significant discrimination between LFT/DFT and between LFT/CA was
      provided by maximum power and spectral slope (dBMHz-1). However, the greatest
      discriminative power was given by the y-axis (0 Hz) intercept of the spectral
      slope: LFT/DFT (p = 0.001); LFT/CA (p = 0.0001); and DFT/CA (p = 0.089).

PMID- 9140179
TI  - Ultrasonic characterization of in vitro osteoarthritic articular cartilage with
      validation by confocal microscopy.
AB  - The majority of adults over the age of 65 y develop osteoarthritis (OA), a joint
      disease characterized by degeneration of articular cartilage and subchondral
      sclerosis. Early in the disease, the articular cartilage surface begins to change
      histologically from a smooth to a rough or fibrillated appearance. A prerequisite
      for any chondroprotective pharmacological intervention is detection of OA in its
      preclinical phase. Current diagnostic imaging modalities, such as radiographs or
      (nuclear) magnetic resonance imaging, either cannot directly image the cartilage
      surface or lack sufficient resolution to detect surface fibrillations. We have
      developed an ultrasonic technique that can be used to characterize these surface
      fibrillations directly. We present our in vitro results with validation by laser
      based confocal microscopic imaging.

PMID- 9140180
TI  - Parametric (integrated backscatter and attenuation) images constructed using
      backscattered radio frequency signals (25-56 MHz) from human aortae in vitro.
AB  - Quantitative ultrasonic tissue characterization using backscattered high
      frequency intravascular ultrasound could provide a basis for the objective
      identification of lesions in vivo. Representation of local measurements of
      quantitative ultrasonic parameters in a conventional image format should
      facilitate their interpretation and thus increase their clinical utility. Toward
      this goal, the apparent integrated backscatter, the slope of attenuation (25-56
      MHz) and the value of the attenuation on the linear fit at 37.5 MHz were measured
      using the backscattered radio frequency signals from in vitro human aortae. Local
      estimations of these ultrasonic parameters from both normal and atherosclerotic
      aortic segments were displayed in a B-scan format. The morphological features of
      these parametric images corresponded well to features of histological images of
      the same regions. The attenuation from 25-56 MHz of seven segments of the medial
      layer (both with and without overlying atheroma) were measured using the
      multinarrow-band backscatter method. The average attenuation in the media at 24
      degrees C +/- 3 degrees C was 45 +/- 16 dB/cm at 25 MHz and 102 +/- 13 dB/cm at
      50 MHz. This work represents progress toward the development of quantitative
      imaging methods for intravascular applications.

PMID- 9140181
TI  - An improved flow evaluation scheme in orifices of different aspect ratios.
AB  - An accurate and reliable method of regurgitant flow calculation is currently
      unavailable. The goal of this study was to define a new general method of flow
      calculation for orifices of different aspect ratios. The success of the method
      relies on matching the imaged flow field distribution obtained by color flow
      mapping (CFM) to a three-dimensional (3D) numerical flow field distribution of
      known geometry. The flow field in three orifices of identical cross-sectional
      area with aspect ratios of 1 (circular), 2 and 4 (elliptical) was evaluated by:
      (a) CFM, (b) 3D echocardiographic imaging, and (c) 3D finite element modeling
      (FEM). The orifice shape and size were accurately estimated by 3D
      echocardiographic imaging. FEM showed that the normalized centerline velocity
      profile of the flow field depends on the orifice aspect ratio. CFM provided a
      good description of the centerline profile for each case. For a given distance
      from the orifice center, the equivelocity contour surface area increases with
      increasing aspect ratio. A simple flow calculation scheme was developed to
      calculate regurgitant flow independent of orifice shape. This improved method
      showed better results than previous studies and may prove to be advantageous when
      analyzing in vivo flow fields with complex geometries.

PMID- 9140182
TI  - Phantoms and automated system for testing the resolution of ultrasound scanners.
AB  - Tissue-mimicking phantoms and an automated system have been developed for testing
      the resolution performance of ultrasound scanners by determining detectability of
      low to higher contrast spherical lesions over the entire depth of field. Axial,
      lateral and elevational resolutions are accounted for simultaneously and equally.
      Tissue-mimicking spherical simulated lesions are either 3 or 4 mm in diameter and
      have one of four different intrinsic material contrasts. For each diameter and
      contrast, there is a set of 109 lesions in a regular array with coplanar centers
      extending from 0.5-15.5 cm in depth. With the scan slice superimposed on the
      spheres, the image is frame-grabbed for automated analysis. A diameter-dependent
      lesion signal-to-noise ratio is computed for each pixel position in the image,
      excluding a 5-mm boundary. Two universal thresholds, resulting from maximization
      of agreement between the automated system and human observers, give rise to a
      depth range, or "resolution zone", over which detection exists for each type
      lesion.

PMID- 9140183
TI  - Tissue equivalent vessel phantoms for intravascular ultrasound.
AB  - A tissue equivalent arterial vessel phantom has been developed for use in
      intravascular ultrasound imaging studies. The phantom material is constructed
      from a cross-linked gelatin matrix to which amorphous silica scattering particles
      are added. The ultrasonic properties (speed of sound, frequency-dependent
      attenuation coefficient and frequency-dependent backscatter coefficient) of the
      phantom material have been characterized at 42 MHz and correspond well with in
      vitro measurements of excised human arterial tissue. The mechanical properties of
      the cast vessel phantoms are controlled by varying the concentration of gelatin
      used in the matrix. Experimentally measured values of the circumferential Young's
      elastic modulus of hard and soft vessel phantoms agree well with values reported
      in the literature for human and canine arterial tissue for transmural pressures
      up to 100 mmHg. The phantoms are therefore suitable models for use in the
      development of new applications of intravascular ultrasound imaging, such as the
      assessment regional arterial elasticity.

PMID- 9140184
TI  - Effects of pulsed ultrasound on the frog heart: III. The radiation force
      mechanism.
AB  - Earlier studies have shown that a single, millisecond duration pulse of
      ultrasound delivered to the frog heart in vivo during systole can produce a
      reduction in the developed aortic pressure, while a pulse delivered during
      diastole can produce a premature ventricular contraction. The threshold for these
      effects is 5-10 MPa with a 5-ms pulse. Since cardiac tissues respond to
      mechanical stimulation, the objective of this study was to investigate acoustic
      radiation force as a possible mechanism for the observed effects of ultrasound on
      the frog heart. In two experiments, the radiation force exerted on the heart was
      varied by varying the ultrasonic frequency and the acoustic beam width. Results
      of these studies indicated that the rate of occurrence of the reduced aortic
      pressure effect was directly correlated with the magnitude of the radiation force
      exerted on the heart. A third experiment tested the radiation force mechanism
      directly by placing an acoustic reflector on the frog heart. The acoustic
      reflector maximized the radiation force delivered to the heart, but eliminated
      direct interaction of the ultrasound with the heart and experimentally eliminated
      heating and cavitation as mechanisms of action. The reduced aortic pressure
      effect was observed with the reflector on the heart, indicating that radiation
      force is capable of producing this effect. No premature ventricular contractions
      were observed with the acoustic reflector over the heart, suggesting that another
      property of the exposure may be responsible for this bioeffect.

PMID- 9140186
TI  - Temperature rise recorded during lesion formation by high-intensity focused
      ultrasound.
AB  - Temperature rise was observed as a function of time in liver and dog prostate
      tissue ex vivo during heating with high-intensity focused ultrasound. The
      temperature rise was measured using a needle thermocouple placed at the focus.
      The temperature vs. time behaviour closely followed the predictions of a model
      based on bulk and surface heating. When the tissue temperature was raised above
      50 degrees C, an increase in heating rate was seen. At higher temperatures, a
      point was reached at which a marked, irreversible change of tissue properties was
      observed, consistent with protein denaturation. The change was sometimes
      accompanied by a sudden further rise in temperature followed by an equally sudden
      fall. On dissection, regions of tissue damage (lesions) were seen, sometimes
      containing bubbles consistent with acoustic cavitation or vaporisation.

PMID- 9140185
TI  - Thresholds for fetal hemorrhages produced by a piezoelectric lithotripter.
AB  - Hemorrhage to fetal tissues occurred when late-term pregnant mice were exposed to
      lithotripter fields of relatively low amplitude. These hemorrhages were always
      observed in tissues near developing bone or cartilaginous structures such as the
      head, limbs and ribs, while soft tissues distant from bone were relatively free
      of hemorrhage. Thresholds for hemorrhage in the fetus were determined for
      exposures of pregnant mice on the 18th day of gestation to 200 pulses from a
      piezoelectric lithotripter. Animals were exposed to axial peak positive pressures
      of either 0 (sham), 1, 2, 3, 5 or 10 MPa. Thresholds for hemorrhage to the head,
      limbs, ribs and lung were all < 1 MPa.

PMID- 9140187
TI  - Hemolysis in vivo from exposure to pulsed ultrasound.
AB  - Ultrasonically induced hemolysis in vivo when a commercial ultrasound contrast
      agent, Albunex, was present in the blood. Murine hearts were exposed for 5 min at
      either 1.15 or 2.35 MHz with a pulse length of 10 microseconds and pulse
      repetition frequency of 100 Hz. During the exposure period, four boluses of
      Albunex were injected into a tail vein for a total of approximately 0.1 mL of
      Albunex. Following exposure, blood was collected by heart puncture and
      centrifuged, and the plasma was analyzed for hemoglobin concentration. With
      Albunex present in the blood, the threshold for hemolysis at 1.15 MHz was 3.0 +/-
      0.8 MPa (mean +/- SD) peak positive pressure (approximately 1.9 MPa negative
      pressure, approximately 180 W cm-2 pulse average intensity). For the highest
      exposure levels (10 MPa peak positive pressure at the surface of the animal), the
      mean value for hemolysis was approximately 4% at 1.15 MHz and 0.46% at 2.35 MHz,
      i.e., the threshold at 2.35 MHz is > 10 MPa peak positive pressure. In contrast,
      hemolysis in control mice receiving saline injections at 10 MPa or sham-exposed
      (0 MPa) mice receiving Albunex was approximately 0.4%.

PMID- 9140188
TI  - Is CD46 the cellular receptor for measles virus?
AB  - Although CD46 would appear to be the cellular receptor for vaccine strains of
      measles virus (MV), recently there has been an accumulation of data suggesting
      that CD46 does not play this role for MV wild-type strains. Clarification of the
      nature of the MV receptor is necessary for the development of more effective
      vaccines against this virus which is responsible for the deaths of nearly two
      million children each year in the Third World.

PMID- 9140189
TI  - A human homolog of the vaccinia virus HindIII K4L gene is a member of the
      phospholipase D superfamily.
AB  - We have identified a human gene encoding a protein with 48% amino acid identity
      to the vaccinia virus (VV) K4L gene product. Both contain motifs characteristic
      of the phospholipase D (PLD) protein superfamily. These proteins are also related
      to vaccinia virus p37, encoded by the F13L gene, which is required for
      envelopment and spread of the virus. The similarity to phospholipase D provides
      insight into the mechanisms and evolution of these processes.

PMID- 9140190
TI  - Nucleotide sequence and transcriptional analysis of a portion of the bovine
      herpesvirus genome encoding genes homologous to HSV-1, UL25, UL26 and UL26.5.
AB  - We determined the nucleotide sequence of a 3,811 base pair (bp) region of the
      bovine herpesvirus type-1 (BHV-1) HindIII-A fragment covering map units 0.429
      0.456, which contained the HSV-1 homologues of the UL25, UL26 and UL26.5 genes.
      Sequence overlap was verified with previously published BHV-1 sequences,
      resulting in contiguous sequence spanning from UL24 to UL27 (encoding
      glycoprotein B). We found that the UL25 open reading frame (ORF) overlapped that
      of UL24 by 16 nucleotides, an unexpected feature based on previous herpesvirus
      sequences. We previously showed that the BHV-1 UL26 and UL26.5 genes encoded
      proteins that functioned in proteinase and scaffolding activity during capsid
      assembly, similar to the homologues in herpes simplex virus type-1. Northern
      blotting was used to map the four major transcripts from this region. As expected
      from the ORF analysis, the BHV-1 UL25 transcript initiated within the UL24 ORF.
      The BHV-1 UL24, UL25, UL26 and UL26.5 transcripts all terminated at a common 3'
      polyadenylation site and varied significantly in their relative abundance.

PMID- 9140191
TI  - Nucleotide sequence of the genes encoding the matrix and small hydrophobic
      proteins of pneumonia virus of mice.
AB  - The nucleotide sequences of the genes encoding the matrix (M) protein and the
      small hydrophobic (SH) protein of pneumonia virus of mice (PVM) are described.
      The matrix protein gene contains a large open reading frame encoding polypeptide
      of 257 residues which shows considerable (38.6-42.1%) amino acid identity with
      the matrix proteins of other pneumoviruses. The matrix gene also contains a
      second, smaller, open reading frame (ORF) as seen with the equivalent genes of
      other pneumoviruses. The PVM second open reading frame is capable of encoding a
      polypeptide of 46 residues and shows no significant similarity with the proteins
      encoded by the equivalent open reading frames of the other pneumoviruses. The
      gene adjacent to that encoding the matrix protein encodes a small, 92 residue,
      polypeptide which has a central hydrophobic domain and is structurally similar to
      the small hydrophobic protein of respiratory syncytial virus.

PMID- 9140192
TI  - Filovirus-like particles detected in the leafhopper Psammotettix alienus.
AB  - Filamentous particles were detected by negative contrast electron microscopy of
      extracts from the leafhopper Psammotettix alienus (Dahlbom) reared on healthy
      Festuca gigantea plants. The particles were straight, slightly curved or
      flexuous, sometimes with the one end curled into a ring with an outer diameter of
      about 200 nm. Length distribution of 280 particles showed a minor and a major
      group with median length of about 600 and 1,100 nm, respectively. Projections, 8
      10 nm long and about 10 nm apart, were evenly distributed on the surface. The
      diameter of particles, including projections, was 55-70 nm. Partly disintegrated
      revealed an internal structure about 30 nm in diameter and with cross-striation
      with a periodicity of 5-5.5 nm. In some particles, a central canal, 5-10 nm in
      diameter, could be seen at one end. Ultramicrotomy of leafhopper heads showed
      that some cells contained intracytoplasmic clusters of particles together with
      filamentous structures. The particles described in this paper resemble virions in
      the virus family Filoviridae, but can be distinguished by having a smaller
      particle diameter. The name Taastrup virus is suggested for the putative virus
      from Psammotettix alienus, according to the place it was first detected.

PMID- 9140193
TI  - Structural and functional heterogeneity of integrated recombinant AAV genomes.
AB  - Adeno-associated Virus (AAV) has emerged as a promising vector for gene therapy
      because of its ability to generate high titer recombinant stocks and the
      potential for site specific integration. However, much of the current knowledge
      regarding the transduction and integration biology of this virus is based on
      studies evaluating wild type AAV or recombinant AAV which was unknowingly
      contaminated with wild type virus. Given the fact that recombinant AAV is
      replication incompetent, by virtue of deleted viral rep proteins responsible for
      site specific integration of the wild type virus, the integration process for
      recombinant AAV may likely be different from its wild type counterpart. To this
      end, the present study has attempted to elucidate the proviral structure of
      stably integrated recombinant AAV genomes harboring the alkaline phosphatase
      reporter gene in 293 and IB3 cell lines. Initial studies attempted to
      functionally characterize differences in proviral genomes using mobilization
      assays with assessed both liberated episomal recombinant AAV and infectious virus
      following transfection with Rep/Cap containing plasmids and/or infection with
      recombinant adenovirus (Ad). Using Southern and polymerase chain reaction (PCR)
      analysis, evaluation of genomic DNA from AAV clonal cell lines indicated that
      head to tail orientations of ITRs were absolutely required for excision of
      episomal genomes and rescue of infectious recombinant virus. Furthermore,
      mobilization of proviral DNA could be achieved in the presence of exogenous
      Rep/Cap without adenovirus, while mobilization of infectious recombinant virus
      required the addition of both Rep/Cap and Ad. Genomic Southerns suggest that two
      predominant proviral structures exist for recombinant AAV including head to head
      and tail to head duplex genomes. A third class of monomer proviral genomes with
      head to tail oriented ITRs was also observed. No evidence for tail to tail ITR
      oriented proviral genomes was detected in any of the clonal cell lines. Such
      findings have begun to lay the foundation for a clearer understanding of the
      mechanism of recombinant AAV integration and how this process differs from wild
      type AAV.

PMID- 9140194
TI  - Analysis of the large (L) protein gene of the porcine rubulavirus LPMV:
      identification of possible functional domains.
AB  - The complete nucleotide sequence of the porcine rubulavirus LPMV (La Piedad
      Michoacan virus) large (L) protein gene was determined and analysed. The L mRNA
      was found to span 6,786 nucleotides, containing one single large open reading
      frame (ORF), putatively encoding a polypeptide of 2,251 amino acids. By aligning
      the amino acid sequence of the LPMV L-protein with L-protein of a number of
      viruses belonging to the order mononegavirale, a high degree of similarity
      between the LPMV L-protein and other rubula virus L-proteins was demonstrated,
      extending through almost the whole protein. Additionally we could identify
      several regions as being highly conserved among all studied viruses of the order
      mononegavirale. The significance of these regions are discussed.

PMID- 9140195
TI  - Interspecies transmission of influenza C virus between humans and pigs.
AB  - The antigenic and genetic characteristics of the 18 human strains of influenza C
      virus isolated in Yamagata and Sendai Cities, Japan between January 1991 and
      February 1993 were investigated. Antigenic analysis with monoclonal antibodies to
      the hemagglutinin-esterase glycoprotein showed that the isolates could be divided
      into three distinct groups closely related to C/Yamagata/26/81, C/Aichi/1/81 and
      C/Mississippi/80, respectively. T1-oligonucleotide fingerprinting of total vRNA
      revealed that the six isolates belonging to the C/Yamagata/26/81 virus group had
      the genomes greatly similar to one another but considerably different from those
      of the 1988/1990 isolates (except C/Yamagata/10/89) of the same antigenic group.
      Comparison of total or partial nucleotide sequences of the seven RNA segments of
      the three strains (C/Miyagi/3/91, C/Miyagi/9/91 and C/Miyagi/2/92) representative
      of the 1991/1993 strains of the C/Yamagata/26/81 virus group with those of the
      previous influenza C isolates obtained from humans and pigs during 1980/1989
      showed that the 1991/1993 strains, like C/Yamagata/10/89, are more closely
      related to viruses isolated from pigs in Beijing, China in 1981/1982 than to any
      of the isolates from humans. This observation suggests strongly that interspecies
      transmission of influenza C virus between humans and pigs has occurred in nature,
      although it is not known whether the virus has been transmitted from pigs to
      humans or from humans to pigs.

PMID- 9140196
TI  - High prevalence of GB virus C/hepatitis G virus infection among the Jewish
      population in Uzbekistan.
AB  - Although a new virus, GB virus C/hepatitis G virus (GBV-C/HGV), has been isolated
      from patients with hepatitis by two different research groups, its prevalence in
      the world and pathogenesis are still unknown. In this study, 92 samples from the
      Jewish population of Uzbekistan were investigated for the prevalence of GBV
      C/HGV. GBV-C/HGV RNA was detected by reverse transcription polymerase chain
      reaction (RT-PCR) using specific primers derived from the 5'-untranslated region
      (5'-UTR). Sequences were analyzed by a molecular evolutionary method. Of 92
      samples, GBV-C/HGV RNA was detected in ten (10.9%), HCV RNA was present in two
      (2.2%), and HBsAg in eight (8.7%). HTLV-I and HIV infection was not detected.
      Single GBV-C/HGV infection was detected in eight (80%), and co-infection with HBV
      or HCV was detected in only two of the GBV-C/HGV infections. Alanine
      aminotransferase (ALT) levels were elevated in three (3.3%), but none with single
      GBV-C/HGV infection had an elevated ALT level. Nine people (90%) with GBV-C/HGV
      infection were distributed under the mean age of the population (P < 0.05).
      Molecular evolutionary analysis showed all GBV-C/HGV strains in this study were
      related to the HGV derived from the US. These results indicate that (1) GBV-C/HGV
      infection is highly prevalent among the Jewish population in Uzbekistan; (2)
      single GBV-C/HGV infections without persistent hepatitis are common; and (3) GBV
      C/HGV infection is present among the younger generation.

PMID- 9140197
TI  - Single amino acid substitutions in Puumala virus envelope glycoproteins G1 and G2
      eliminate important neutralization epitopes.
AB  - Two monoclonal antibody escape virus mutants (MARs), rescued from a human MAb to
      glycoprotein 2 (G2) and a bank vole monoclonal antibody (MAb) directed to
      glycoprotein 1 (G1) of Puumala virus, strain Sotkamo, were produced by using a
      combination of neutralization tests and antigen detection. The MARs and the
      original virus were analyzed by nucleotide sequencing and the responsible
      mutations were defined and characterized. The G1 mutation was found to constitute
      an A to T nucleotide substitution, giving raise to an aspartic acid to valine
      mutation at residue 272, potentially increasing the hydrophobicity of this
      region. The G2 mutation was found to constitute a C to T substitution, altering
      the residue 944 from serine into the more hydrophobic phenylalanine and resulting
      in secondary structure alterations. The mutation was found to be in close
      vicinity to a glycosylation site. Synthetic peptides covering the regions of the
      native virus, defined by the MARs, were produced and evaluated for reactivity
      with the corresponding MAb. The peptides were not recognized by the MAbs, and did
      not inhibit the binding of the MAbs in competition assays. Sera from mice
      immunized with the peptides were not able to recognize the native protein. This
      indicates that the epitopes are non-linear and/or glycosylated in the native
      state, or alternatively, that the G1 and G2 MAbs binds to regions away from the
      mutations.

PMID- 9140198
TI  - Bovine coronavirus I protein synthesis follows ribosomal scanning on the
      bicistronic N mRNA.
AB  - The mRNA encoding the 49-kDa nucleocapsid protein (N) of the bovine coronavirus
      is bicistronic. A 23-kDa protein, termed the I protein for the 'internal' open
      reading frame (ORF), is also synthetized but in the +1 reading frame beginning 61
      nt downstream of the N start codon. Sequences flanking the N and I start codons
      suggest that the I ORF might be accessed by scanning ribosomes passing over the N
      start codon. Here we test this idea and demonstrate with translation studies both
      in vitro and in vivo that the I protein is synthesized according to the leaky
      scanning model for initiation of translation on the subgenomic N mRNA molecule.

PMID- 9140199
TI  - Computational study of packing a collagen-like molecule: quasi-hexagonal vs
      "Smith" collagen microfibril model.
AB  - The lateral packing of a collagen-like molecule, CH3CO-(Gly-L-Pro-L-Pro)4-NHCH3,
      has been examined by energy minimization with the ECEPP/3 force field. Two
      current packing models, the Smith collagen microfibril twisted equilateral
      pentagonal model and the quasi-hexagonal packing model, have been extensively
      investigated. In treating the Smith microfibril model, energy minimization was
      carried out on various conformations including those with the symmetry of
      equivalent packing, i.e., in which the triple helices were arranged equivalently
      with respect to each other. Both models are based on the experimental observation
      of the characteristic axial periodicity, D = 67 nm, of light and dark bands,
      indicating that, if any superstructure exists, it should consist of five triple
      helices. The quasi-hexagonal packing structure is found to be energetically more
      favorable than the Smith microfibril model by as much as 31.2 kcal/mol of five
      triple helices. This is because the quasi-hexagonal packing geometry provides
      more nonbonded interaction possibilities between triple helices than does the
      Smith microfibril geometry. Our results are consistent with recent x-ray studies
      with synthetic collagen-like molecules and rat tail tendon, in which the data
      were interpreted as being consistent with either a quasi-hexagonal or a square
      triangular structure.

PMID- 9140200
TI  - The effect of N-methylation on helical peptides.
AB  - In N-methyl amino acids, the hydrogen of the N-H group is replaced with a bulky
      methyl group. While this change is expected to destabilize helical structures,
      the amount of destabilization is not known. Here the N-methyl group is placed
      into several positions of the helical peptides, acetyl-WGG(EAAAR)4A-amide and
      acetyl-WGG(RAAAA)4R-amide, and the melting of the peptides followed using CD.
      When analyzed using a simple two-state model, the destabilization associated with
      the H to CH3 substitution at 0 degree C is between 0.3 to 1.7 kcal/mole and is
      position dependent. The melting data may also be analyzed using a modified form
      of the Lifson-Roig statistics that should more correctly model the helix-coil
      transition in this small peptide. This analysis fails, however, apparently
      because the destabilization energy is greater than the energy that can be
      attributed to a single residue in this model.

PMID- 9140201
TI  - Nonspecific protease-catalyzed hydrolysis/synthesis of a mixture of peptides:
      product diversity and ligand amplification by a molecular trap.
AB  - We sought to develop a peptide library in solution and dynamically screen this
      library for peptides that would bind to macromolecules of interest. Peptide
      diversity was achieved in an initial stock solution of peptides by using
      proteases under conditions in which both hydrolysis and synthesis occurred. As an
      example, a simple reaction containing YGG, FL and thermolysin resulted in the
      synthesis of YGGFL as well as many other undefined products. When low molecular
      weight products of a reaction containing VA, AL, and thermolysin were
      subsequently exposed to dipeptidase, 7 out of 9 potential dipeptides were
      observed. Incubation of protease with an hydrolysate of albumin and a
      radiolabeled peptide resulted in the radiolabel participating in reactions other
      than simple hydrolysis and, after 24 h, the specific activity of radiolabel was
      shown by high performance liquid chromatography to disperse to a level that would
      be necessary in the event of maximum theoretical diversity. When a binding
      macromolecule was exposed to this system, ligand production was amplified
      relative to reactions run in the absence of binding macromolecule. This protease
      based peptide scrambling and binding system was utilized for the discovery of
      novel peptides that bind to fibrinogen.

PMID- 9140202
TI  - Conformational characterization of a peptide mimetic of the third cytoplasmic
      loop of the G-protein coupled parathyroid hormone/parathyroid hormone related
      protein receptor.
AB  - The third-cytoplasmic loop of the G-protein coupled receptor responsible for the
      activity of parathyroid hormone and parathyroid hormone-related protein has been
      structurally characterized in aqueous solution in the presence of sodium
      dodecylsulfate and dodecylphosphocholine micelles. The high-resolution
      conformation of the 29-amino acid peptide containing the sequence of the
      cytoplasmic loop was obtained by CD and nmr. The structure was refined using a
      two-step distance geometry based method that first includes the removal of all
      side chains to quickly locate the globular fold of the peptide. After a simulated
      annealing protocol, the side chains are added in a random fashion. The resulting
      conformation was further refined with nuclear Overhauser enhancement restrained
      molecular dynamics using a two-phase simulation cell consisting of carbon
      tetrachloride and water as a mimetic of the biphasic, hydrophobic/hydrophilic
      character of the micelles in which the experimental measurements were carried
      out. The topological orientation of the cycloplasmic loop within the micelle was
      determined by addition of 5-doxylstearate and monitoring the decrease of nmr
      signal intensities from the radical-induced relaxation. The conformation and
      relative orientation of the peptide provided insight into the mechanism by which
      the cytoplasmic portion of the receptor activates the heterotrimeric, guanine
      nucleotide-binding regulatory protein, one of the first steps in signal
      transduction.

PMID- 9140203
TI  - Reliability of a hand gripping endurance test.
AB  - The aim of this study was to assess the reproducibility of a new endurance test
      for hand grip movements. On six occasions separated by at least 3 days, 30
      healthy subjects performed six maximal endurance tests in two different positions
      with a hand grip tool attached to an isokinetic dynamometer. The test consisted
      of repeated maximal grip movements (1-min bouts for men and 30-s bouts for women
      subjects) at an angular velocity of 45 degrees/s. A custom-made PC programme was
      used to collect data on peak torque and mechanical work, and to provide the
      following parameters: basal torque, basal work, time until basal values fell to
      20, 30 and 50% of the initial peak values, slopes of decay of torque and work
      over time. The intraclass correlation coefficient (ICCC) was then computed to
      assess the reproducibility of the parameters obtained during the tests. An
      'almost perfect' (0.8 < ICCC = 1) reproducibility of the basal torque values in
      both positions and a 'substantial' (0.6 < ICCC = 0.8) or 'almost perfect'
      reproducibility of the slope values referred to the torque decay over time was
      observed. Feasible applications of this new endurance test in ergonomics and
      vocational rehabilitation are discussed.

PMID- 9140204
TI  - Improving office work: a participatory ergonomic experiment in a naturalistic
      setting.
AB  - In a Department of Salary Records where VDU tasks were performed at a high work
      rate, a participative ergonomic study was undertaken. First, the 'old' workplace
      was investigated for all 45 employees. Work stations appeared to be of poor
      ergonomic quality. Second, 12 employees participated in an experiment at the
      actual workplace. Objective and subjective effects were recorded under three
      conditions: the 'old' workplace, the recommended ('ideal') workplace, and the
      self-chosen workplace. Based on this data 'ergonomic' furniture and additional
      accessories were ordered and all 45 employees received tailor-made instructions
      and training with respect to their ideal workplace. After 5 months data for their
      'objective' workplaces and subjective reports about the workplace were recorded.
      The study focuses on the comparison of the three conditions and of the two groups
      of employees: 33 who received thorough instruction and training only, and 12 who
      also participated in the experiment. Both objective and subjective improvements
      are demonstrated in the recommended situation when compared to the original
      situation. Although some employees deliberately chose to deviate from the
      recommended situation--owing to task and individual characteristics--self chosen
      workplaces still constituted a much better workplace in comparison to the old
      workplace. The 12 employees who participated in the experiment chose a better
      self-preferred workplace when compared to their 33 colleagues. It is concluded
      that experimental measurements in a naturalistic setting may contribute
      significantly to workplace improvements (1) by presenting adequate and
      'objective' information for workplace improvement and ergonomic redesign, and (2)
      as a change agent itself, that is as an 'intensified treatment'.

PMID- 9140205
TI  - Automatic calculation of the medial axis of foot outline and its flexion angles.
AB  - As one of the morphological characteristics of human foot, flexion angles of
      medial axis of foot outline have been proposed in order to improve shoe comfort.
      Foot outlines were easily obtained by a scriber, whereas calculation of the
      medial axis and its flexion angles from the foot outline had inter-operator
      errors and a lack of reproducibility. This is because foot outlines were inputted
      by a digitizer, and flexion points of the medial axis were determined by eye
      inspection. An automatic method of calculation was developed for the following
      purposes: (1) to decrease inter-operator errors caused by manual operation; (2)
      to improve the reproducibility of the medial axis and its flexion angles; and (3)
      to save time and trouble in processing a large amount of data. The flexion angle
      reproducibility of the present method was within 1 degree. The errors in the
      flexion angles determined by the present method are half those determined by the
      conventional method. The flexion angles of over 5000 foot outlines that were
      obtained in 1987 were calculated when the present method was developed. The mean
      posterior flexion angle of the adults was 8.4 degrees. Since the majority of
      Japanese feet are outflared, this characteristic should not be ignored in
      designing/modifying shoe lasts.

PMID- 9140206
TI  - The influence of gloves during maximum volitional torque exertion of supination.
AB  - This study focuses on the influence of friction between gloves and handle surface
      during maximum volitional torque exertion of supination (S-MVTE) and under both
      friction-controlled and regular friction conditions. Forty student subjects (20
      males and 20 females) participated in this study. Five types of gloves (surgical,
      single cotton, double cotton, leather, and rubber), seven handle sizes (25.4,
      31.8, 38.1, 44.5, 50.8, 57.2, and 63.5 mm in diameter) and two handle shapes
      (cylindrical and hexagonal) were evaluated to determine their combined influences
      on S-MVTE. The barehanded condition was also included for comparison. The results
      indicate that all the main effects were significant (P < 0.001). Under friction
      controlled conditions (oiled surface handle), the S-MVTEs with gloves were found
      to be greater than the S-MVTEs of the gloveless, and the thicker the gloves, the
      greater the S-MVTE. On the other hand, under regular (unoiled) conditions, the S
      MVTE was mainly affected by the friction between handle surface and gloves,
      although the interaction between gloves and handle shape was also a minor
      influence. A hexagonal handle produced, in all handle diameters, greater S-MVTE
      than a cylindrical handle. The mean S-MVTE under oiled conditions was about 53%
      of that of unoiled conditions. The mean S-MVTE of females was about 61% of that
      of males.

PMID- 9140207
TI  - The use of Taguchi's methods for the evaluation of industrial knife design.
AB  - Knives are used in industry, and particularly on meat packaging assembly lines,
      where a premium is placed on the speed of cutting. One consequence of this is
      that knife design and selection has been based on the speed of cutting as the
      most significant measure of a knife. In industry the cuts that knives make vary
      in difficulty with many factors such as thickness, contour, and temperature of
      the material being cut. These factors may change the speed with which these cuts
      are made. According to Taguchi's methods, a robust design is one that maintains
      high performance while remaining insensitive to changes in its environment. This
      means that a robust knife design would enable an employee to cut not only with as
      much speed as possible in one particular cutting scenario, but also with a
      consistently high speed in as many cutting scenarios as possible. An experiment
      with various knife designs was evaluated with Taguchi's method. Ten subjects cut
      outlined clay patterns in 15 min with each one of nine different knives. The nine
      different designs were generated from the following combinations; three grip
      sizes (44.4, 50.8 and 63.5 mm), three coupling angles between the grip and the
      blade (0, 45 and 90 degrees), three blade heights measured from the middle of the
      blade (10, 13 and 15 mm), and three blade lengths (85, 125 and 155 mm). Eight
      conditions of cutting material were used to generate 'noise'. They are
      combinations of temperature of the clay to be cut (from temperature (R)
      approximately 25 degrees C, frozen for 1 h (F) approximately 5 degrees C),
      thickness of the clay to be cut (15 and 25 mm), and orientation of the work
      surface (0 and 30 degrees). The result shows that the knife design of 63.5 mm
      grip size, 0 degree coupling angle, 13 mm blade height, and 85 mm blade length
      provides the highest number of cuts, the knife design of 50.8 mm grip size, 45
      degrees coupling angle, 15 mm blade height, and 85 mm blade length gives the
      highest signal to noise ratio. The shorter blade (85 mm) is suggested by both
      designs, but the two designs are different in the other three variables. Further
      analysis of the noise variables shows that lowering clay temperature
      significantly reduces cutting speed. Although there is more than one design that
      can resolve changes in clay thickness and clay orientation, a 15 mm blade height
      is the only design insensitive to the clay temperature change.

PMID- 9140208
TI  - Determination of peak oxygen uptake during upper body exercise.
AB  - The purpose of this study was to determine (1) the repeatability of a currently
      recommended protocol for determination of VO2 peak during upper body exercise
      involving a crank rate of 60 rev min-1 (Hale et al. 1988), (2) whether employing
      a higher crank rate (70 rev min-1) elicits higher VO2 peak values; (3) whether
      including an additional exercise stage 5 min after volitional exhaustion would
      elicit higher VO2 peak values. Twenty subjects (mean +/- SD) age, height and body
      mass were 22.8 +/- 1.8 years, 176 +/- 5.0 cm and 77.5 +/- 4.0 kg, respectively)
      visited the laboratory on three separate occasions. Subjects performed a
      different test to determine upper body VO2 peak on each visit. The tests were
      continuous and incremental in nature and were performed on a Monark cycle
      ergometer (Model 814E) adapted for arm exercise. Test 1 required subjects to
      exercise at a crank rate of 60 rev min-1 (60RPM-1). Test 2 was identical to test
      1 (60RPM-2) but after 5 min recovery from the test subjects performed a further
      exercise stage (60RPM-F). Test 3 employed a crank rate of 70 rev min-1 (70RPM).
      Five minutes after volitional exhaustion a further exercise stage was performed
      (70RPM-F). The levels of agreement for the 60 rev min-1 protocol were +/-0.50 1
      min-1. All VO2 peak values achieved were within these limits. However, a higher
      VO2 peak was achieved by employing a crank rate of 70 rev min-1 (p < 0.05). The
      VO2 peak achieved for 60RPM-F was similar to 60RPM whereas the VO2 peak for 70RPM
      F tended to be less than that for 70RPM (p = 0.064). The results of this study
      suggest that the 60 rev min-1 protocol can reliably determine VO2 peak, however
      it would appear to be more appropriate to employ a 70 rev min-1 protocol as
      higher values were attained.

PMID- 9140209
TI  - The effects of different thermal environments on the physiological and
      psychological responses of firefighters to a training drill.
AB  - Little is known about the impact of thermoregulatory demands on cardiovascular
      and psychological responses of firefighters during firefighting activities. This
      study examined selected responses to a training drill in different thermal
      environments. Male firefighters (n = 16) were randomly assigned to perform a
      simulated ceiling overhaul task for 16 min in either a neutral (13.7 degrees C)
      or hot (89.6 degrees C) condition while wearing standard firefighting turnout
      gear. Physiological and psychological measures were assessed before, after 8 min
      and 16 min of firefighting activity, and following a 10-min recovery period. The
      variables assessed included heart rate (HR), tympanic temperature (Ttymp),
      lactate level (LAC), blood glucose level, ratings of perceived exertion (RPE),
      perceptions of respiration, thermal sensations (TS) and state anxiety (SA).
      Significant increases were seen for HR, Ttymp, LAC, RPE and SA, with the
      increases being much greater following the hot condition. Recovery was
      significantly slower following work in the hot condition. These findings suggest
      that the addition of a live fire (a common situation for firefighters)
      contributes to increased cardiovascular and psychological strain at a
      standardized workload.

PMID- 9140210
TI  - Influence of vanadium on acclimatization of humans to high altitude.
AB  - The study was conducted on human volunteers as controls as well as after
      administration of vanadyl sulphate on induction to high altitude (HA) at 3500 m.
      The plasma vanadium contents were significantly reduced in the control group on
      abrupt induction to HA on days 3 and 10, indicating redistribution to other
      organs/tissues under the stressful situation. In the vanadium salt-treated group,
      plasma vanadium contents were similar to those obtained at sea-level.
      Administration of vanadyl sulphate did not act as a diuretic. Moreover the
      vanadium supplemented group drank more water and also excrete less urine than the
      control group.

PMID- 9140211
TI  - The effect of change in skin temperature due to evaporative cooling on sweating
      response during exercise.
AB  - The purpose of this study was to investigate whether there are any effects of
      skin temperature changes on sweating response in the first few minutes of mild
      exercise. Six healthy males performed a bicycle exercise at 100 W (50 rpm) for 30
      min under an ambient temperature of 23 degrees C (40% RH). Esophageal temperature
      (Tes), mean skin temperature (Tsk), local skin temperature at the lower left
      scapula (Tsl), local sweating rate (Msw) and cutaneous blood flow by laser
      Doppler flowmetry (LDF) were measured continuously. Although Tsl decreased
      markedly just after the onset of sweating, Tsk did not change. Msw did not
      increase constantly in the early stages of exercise, and there was a temporary
      interruption in the increase of Msw. This interruption in sweating was affected
      by the rate of change in Tsl rather than by the absolute value of Tsl, since
      there was a positive and significant correlation between the time of the
      interruption in the increase of Msw and the rate of decrease in Tsl (y = 6.47 x
      +0.04; r = 0.86, P < 0.05). The results suggest that sweating response in the
      early stages of exercise may be influenced by changes in local skin temperature
      due to evaporative cooling.

PMID- 9140212
TI  - Oral temperatures of the elderly in nursing homes in summer and winter in
      relation to activities of daily living.
AB  - This study was conducted to clarify the seasonal difference in body temperature
      in summer and winter, and to document the thermal environment of the elderly
      living in nursing homes. The subjects were 57 healthy elderly people aged > or =
      63 years living in two nursing homes in Japan. One of the homes was characterized
      by subjects with low levels of activities of daily living (ADL). Oral
      temperatures were measured in the morning and afternoon, with simultaneous
      recording of ambient temperature and relative humidity. Oral temperatures in
      summer were higher than in winter, with statistically significant differences (P
      < 0.05) of 0.25 (SD 0.61) degree C in the morning and 0.24 (SD 0.50) degree C in
      the afternoon. Differences between oral temperatures in summer and winter tended
      to be greater in subjects with low ADL scores, even when their room temperature
      was well-controlled. In conclusion, the oral temperatures of the elderly are
      lower in winter than summer, particularly in physically inactive people. It
      appears that those with low levels of ADL are more vulnerable to large changes in
      ambient temperature.

PMID- 9140213
TI  - Physical effects of negative air ions in a wet sauna.
AB  - The physical effects of negative air ions on humans were determined in an
      experimental sauna room equipped with an ionizer. Thirteen healthy persons took a
      wet sauna bath (dry bulb temperature 42 degrees C, relative humidity 100%, 10 min
      exposure) with or without negative air ions. The subjects were not told when they
      were being exposed to negative air ions. There were no differences in the moods
      of these persons or changes in their blood pressures between the two saunas. The
      surface temperatures of the foreheads, hands, and legs in the sauna with negative
      ions were significantly higher than those in the sauna without ions. The pulse
      rates and sweat produced in the sauna with ions were significantly higher than
      those in the sauna without ions. The results suggest that negative ions may
      amplify the effects on humans of the sauna.

PMID- 9140214
TI  - Space proton flux and the temporal distribution of cardiovascular deaths.
AB  - The influence of solar activity (SA) and geomagnetic activity (GMA) on human
      homeostasis has long been investigated. The aim of the present study was to
      analyse the relationship between monthly proton flux (> 90 MeV) and other SA and
      GMA parameters and between proton flux and temporal (monthly) distribution of
      total and cardiovascular-related deaths. The data from 180 months (1974-1989) of
      distribution in the Beilinson Campus of the Rabin Medical Centre, Israel, and of
      108 months (1983-1991) from the Kaunas Medical Academy, were analysed and
      compared with SA, GMA and space proton flux (> 90 MeV). It was concluded: (1)
      monthly levels of SA, GMA and radiowave propagation (Fof2) are significantly and
      adversely correlated with monthly space proton flux (> 90 MeV); (2) medical
      biological phenomena that increase during periods of low solar and/or geomagnetic
      activity may be stimulated by physical processes provoked by the concomitant
      increase in proton flux; (3) the monthly number of deaths related (positively or
      negatively) to SA are significantly and adversely related to the space proton
      flux (> 90 MeV).

PMID- 9140215
TI  - Monthly distribution of multiple sclerosis patients' births.
AB  - As part of an integrated geographical and environmental epidemiological study of
      multiple sclerosis (MS) in Budapest's Pesterzsebet district, many
      biometeorological variables were specifically examined. Also, the monthly
      distribution of birthdates of MS patients resident in the district was plotted.
      Patients reliably diagnosed with MS were found to have been born in greater
      numbers in the months of April and October, precisely 6 months apart. This
      finding indicates the presence of natural non-genetic factors in the creation of
      MS susceptibility, affecting the nervous system at the crucial time of
      myelination.

PMID- 9140216
TI  - Skin-color preferences and body satisfaction among South Asian-Canadian and
      European-Canadian female university students.
AB  - Skin-color preferences and body satisfaction among 100 South Asian-Canadian and
      100 European-Canadian female university students were examined. South Asian
      Canadian females were found to desire lighter skin than they possessed and had
      lower body satisfaction compared with European-Canadian females. Among South
      Asian-Canadians, the desire to be lighter skinned was greater the more
      participants differed from the cultural White ideal. Light- and medium-skinned
      South Asian-Canadians had the highest and lowest levels of body satisfaction,
      respectively.

PMID- 9140217
TI  - The effects of race, weight, and gender on evaluations of writing competence.
AB  - This study examined the potential interactive effects of target race, weight, and
      gender on American Caucasian students' ratings of writing competency. Stimulus
      materials were eight articles in a newspaper byline format with photographs of
      the authors that conveyed the characteristics of race (African
      American/Caucasian), weight (overweight/nonoverweight), and gender (male/female).
      The participants were given eight articles and were asked to rate the writing
      competency of the author on the four qualities of style, clarity, logic, and
      overall writing ability/competency. The results showed that the women gave higher
      style, logic, and overall writing ability/competency ratings than did the men,
      and overweight authors received higher ratings of logic than nonoverweight
      authors. The men gave female Caucasian authors lower ratings of clarity than did
      female participants.

PMID- 9140218
TI  - Representations of eating among adolescent Italian girls.
AB  - The representations of eating of 200 adolescent girls, 100 obese and 100 of
      normal weight, were examined. Factor analysis was used to detect any qualitative,
      quantitative, or structural differences between the two groups' representations
      of eating. The results indicated a difference in the emotional characteristics of
      the representation: Obese participants not only failed to recognize the
      "abnormality" of overeating but considered it "ideal" because of what they
      perceived to be its components of strength and power.

PMID- 9140219
TI  - Activity of extracts and alkaloids of thai Alstonia species against human lung
      cancer cell lines.
AB  - Methanol extracts of root barks of Alstonia macrophylla, A. glaucescens, and A.
      scholaris, collected from Thailand, have been assessed for cytotoxic activity
      against two human lung cancer cell lines, MOR-P (adenocarcinoma) and COR-L23
      (large cell carcinoma), using the SRB assay. Significant cytotoxic activity was
      exhibited by the extract of A. macrophylla on both cell lines. Activity-directed
      fractionation led to the isolation of a novel indole alkaloid, O
      methylmacralstonine, from the most active fraction of A. macrophylla along with
      four known alkaloids, talcarpine, villalstonine, pleiocarpamine, and
      macralstonine. Structure elucidation of the novel alkaloid was based on
      spectroscopic methods, especially 2D-NMR. The bisindole villalstonine was found
      to possess pronounced activity on both cell lines with an IC50 value less than 5
      muM, but was about 10(3) times less potent than vinblastine sulphate. The
      monomeric alkaloid, talcarpine, was found to be inactive. Pleiocarpamine, O
      methylmacralstonine and macralstonine were all considerably less active than
      villalstonine.

PMID- 9140220
TI  - Inhibitory activity of soyasaponin II on virus replication in vitro.
AB  - The antiviral activities of two saponins, soyasaponin I and II, isolated from
      soybean (Glycine max Merrill) were studied in vitro against herpes simplex virus
      type 1 (HSV-1). Soyasaponin II was more potent than soyasaponin I as shown by
      reduction of HSV-1 production. Soyasaponin II was also found to inhibit the
      replication of human cytomegalovirus, influenza virus, and human immunodeficiency
      virus type 1. The action was not due to inhibition of virus penetration and
      protein synthesis, but might involve a virucidal effect. When acyclovir and
      soyasaponin II were evaluated in combination for anti-HSV-1 activity, additive
      antiviral effects were observed for this virus.

PMID- 9140221
TI  - Dual inhibitory activities of tannins from Hamamelis virginiana and related
      polyphenols on 5-lipoxygenase and lyso-PAF: acetyl-CoA acetyltransferase.
AB  - In the present study, the effects of tannins obtained from various plant sources
      on the activity of 5-LOX and AT were examined. With IC50 values ranging from 1.0
      to 18.7 muM, hamamelitannin and the galloylated proanthocyanidins isolated from
      Hamamelis virginiana L. were found to be most potent inhibitors of 5-LOX. Unlike
      the 5-LOX study, hamamelitannin proved to be ineffective in the AT assay. Potent
      candidates are represented by the group of B-type proanthocyanidins. Structure
      activity relationships regarding the in vitro inhibitory potency of the
      polyphenols in the biological assays are discussed.

PMID- 9140222
TI  - Inhibition of 5 alpha-reductase and aromatase by the ellagitannins oenothein A
      and oenothein B from Epilobium species.
AB  - Species of the genus Epilobium (Onagraceae) have been investigated for their
      activity against 5 alpha-reductase and aromatase, two enzymes which are involved
      in the aetiology of benign prostatic hyperplasia (BPH). Activity-guided
      fractionation has led to the identification of two macrocyclic ellagitannins,
      oenothein A (1) and oenothein B (2), as the main constituents responsible for the
      inhibition of the two enzymes. Quantitation of oenothein B in 10 different
      species of Epilobium has shown that amounts of up to 14% in the crude plant
      extracts are possible.

PMID- 9140223
TI  - Effect of Glycyrrhiza glabra roots and glycyrrhizin on the glucuronidation in
      rats.
AB  - As an approach to elucidate the possible in vivo interaction of synthetic drugs
      and herbs which are frequently used in combination in Asia, the effect of
      Glycyrrhiza glabra on the metabolism of acetaminophen (AAP) was examined in male
      Sprague-Dawley rats. The pretreatment of the methanol extract of Glycyrrhiza
      glabra roots (Glycyrrhizae Radix, GR, 1 g/kg, p.o.) for 6 days significantly
      increased the cumulative biliary (156%) and urinary (132%) excretions of AAP
      glucuronide conjugate within 120 min after the administration of AAP (150 mg/kg,
      i.v.) without affecting thioether and sulfate conjugates. These findings suggest
      that GR might enhance the glucuronidation pathway of AAP. In order to study the
      effect of GR on the glucuronidation in rat liver, we examined enzymatic activity
      of p-nitrophenol UDP-glucuronosyltransferase (UGT), which is also called UGT1A,
      and intracellular concentrations of hepatic UDP-glucuronic acid, upon the
      administration of GR (1 g/kg, p.o.) or glycyrrhizin (23 mg/kg, p.o.), a major
      component of GR, for 6 days. GR and glycyrrhizin caused increases in specific
      activities of UGT1A by 111% and 96%, respectively. Concentration of UDP
      glucuronic acid was increased 257% by GR and 484% by glycyrrhizin. These data
      indicate that GR and glycyrrhizin activated glucuronidation and thus suggest the
      possibility that GR may influence detoxification of xenobiotics in rat liver.
      Using the p-nitrophenol UGT1A1 cDNA as a probe, we found that the activation of
      UGT1A by GR was not due to the induction of mRNAs for the enzyme.

PMID- 9140224
TI  - In vitro antispasmodic compounds of the dry extract obtained from Hedera helix.
AB  - Commercial dry extract of Hedera helix L. is used for the treatment of disorders
      of the respiratory tract; it is standardized towards papaverine (papaverine
      equivalent value, PE, activity of 1 g test substance equivalent to the activity
      of x mg papaverine) by in vitro antispasmodic activity on isolated guinea-pig
      ileum with acetylcholine as spasmogen. In order to determine the phytochemical
      basis for the antispasmodic activity, bioassay guided fractionation and
      subsequent isolation of phenolic compounds (flavonols, caffeoylquinic acids) and
      saponins (hederacoside C, alpha-hederin, hederagenin) was carried out. Fractions
      and isolates obtained were investigated for antispasmodic activity and their
      contribution to the activity of the extract was calculated. Significant activity
      was found for both saponins and phenolic compounds, the PE values being approx.
      55 and 49 for alpha-hederin and hederagenin, 54 and 143 for quercetin and
      kaempferol, and 22 for 3,5-dicaffeoylquinic acid, respectively. In view of their
      relative high concentration the saponins contribute most to the anti-spasmodic
      activity, followed by dicaffeoylquinic acids and the flavonol derivatives. The
      results indicate that the summed PE value of the compounds mentioned is an
      acceptable agreement with the PE value of the whole extract determined
      biologically.

PMID- 9140225
TI  - Endothelium-dependent higenamine-induced aortic relaxation in isolated rat aorta.
AB  - The pharmacological action of higenamine in isolated rat aorta was investigated.
      Although the beta-adrenoceptor antagonist propranolol (1 x 10(-5) M) completely
      blocked the beta-adrenoceptor agonist higenamine in inducing a positive
      chronotropic activity in isolated mouse atria, the higenamine-induced aortic
      relaxation was not completely antagonized by this concentration of propranolol.
      The present data also demonstrate that the higenamine-induced aortic relaxation
      was attenuated in the absence of endothelium. These findings suggest that the
      beta-adrenoceptor specificity to higenamine in aorta is different from that of
      beta-1 in atria; moreover, the beta-adrenoceptors sensitive to higenamine are
      mainly located in the endothelial layer.

PMID- 9140226
TI  - The leaf essential oil of Psidium guyanensis offers protection against
      pentylenetetrazole-induced seizures.
AB  - The essential oil obtained from the leaves of Psidium guyanensis Pers.
      (Myrtaceae) was studied against lethal seizures induced by intraperitoneal
      injection of pentylenetetrazole (80 mg/kg), picroptoxin (6 mg/kg), and strychnine
      (2 mg/kg) in mice. At oral doses of 100, 200, and 400 mg/kg, the essential oil
      attenuated the severity of pentylenetetrazole-induced seizures and offered a dose
      related protection but it was found to be ineffective against convulsions induced
      by picrotoxin and strychnine. The blockade of its protective effect on
      pentylenetetrazole lethal seizures by caffeine (10 and 50 mg/kg, i.p.) suggests a
      probable participation of endogenous adenosine in its mechanism. Furthermore, a
      peripheral mechanism also appears to be involved as the essential oil (5-20
      micrograms/ml) was able to block selectively the acetylcholine (1.65 x 10(-6) M)
      induced contractions but not those evoked by high potassium (80 mM) or caffeine
      (2 x 10(-3) M) on isolated toad rectus abdominis muscle.

PMID- 9140227
TI  - Protective effects of red ginseng saponins against carbon tetrachloride-induced
      hepatotoxicity in Sprague Dawley rats.
AB  - The protective effects of red ginseng saponins against carbon tetrachloride
      induced hepatotoxicity were investigated in male Sprague Dawley rats. The total
      saponins of red ginseng standardized on ginsenosides-Rb1, -Rb2, -Rc, -Rd, -Re,
      and -Rg1 were used in the present study. The rats were administered the
      standardized saponins of red ginseng orally at 50, 100, and 200 mg/kg for 7
      consecutive days, followed by an administration of carbon tetrachloride at 0.4
      ml/kg in corn oil intraperitoneally for 24 h. The administration of saponin
      changed neither body and organ weights nor hematological and serum clinical
      parameters. The elevation of SGPT and SGOT activities induced by carbon
      tetrachloride was partially recovered by the administration of the saponin. The
      liver vacuolization and lymphoid cell aggregation by carbon tetrachloride were
      clearly recovered by the red ginseng saponins as examined histologically. The
      present results indicated that the standardized saponins of red ginseng used in
      these studies may partially recover the hepatotoxicity induced by carbon
      tetrachloride in male Sprague Dawley rats.

PMID- 9140228
TI  - Inhibitory effects of oren-gedoku-to and its components on cholesteryl ester
      synthesis in cultured human hepatocyte HepG2 cells: evidence from the cultured
      HepG2 cells and in vitro assay of ACAT.
AB  - The pharmacological effects of Oren-gedoku-to (OGT), a Japanese-Chinese
      traditional herbal medicinal mixture on lipid biosynthesis were investigated in
      cultured human hepatocyte HepG2 cells. The addition of OGT (0.5 and 4.2 mg/ml),
      which had no effect on cell proliferation and cellular protein content, caused a
      marked decrease in the cellular cholesterol content, particularly cholesteryl
      ester content following 24 h incubation. The incorporation of 14C-oleate into
      cellular cholesteryl ester fraction was also reduced remarkably during incubation
      for 6 and 24 h. The effects of OGT, its components and its main active chemicals
      on acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity were studied in
      vitro to explore the mechanism by which OGT inhibits cholesteryl ester formation.
      The data confirmed that OGT, in a dose-dependent manner, and its components
      (Scutellaria baicalensis, Coptis japonica, Gardenia jasminoides and Phellodendron
      amurense) remarkably inhibit ACAT activity. Among the main active chemicals of
      OGT, baicalein, a kind of flavonoid, decreased ACAT activity in a dose-dependent
      fashion from the level of 10(-6)M. These results strongly suggest that OGT
      reduces the cholesteryl ester formation in human hepatocytes by inhibiting ACAT,
      and that baicalein may, in part, be responsible for ACAT inhibition.

PMID- 9140229
TI  - Investigations on the gastroprotective and antidiarrhoeal properties of ternatin,
      a tetramethoxyflavone from Egletes viscosa.
AB  - The study was designed to verify the gastroprotective and antidiarrhoeal effects
      of ternatin, tetramethoxyflavone isolated from Egletes viscosa Less. The
      gastroprotective function of ternatin was evaluated in rats against gastric
      mucosal damage induced by hypothermic restraint stress, absolute ethanol, and
      indomethacin, whereas the antidiarrhoeal activity was investigated by studying
      its influence on gastrointestinal transit as measured by a charcoal marker and on
      castor oil-induced accumulation of intestinal fluid in mice and also on
      contractile responses evoked by acetylcholine, histamine, serotonin, and barium
      chloride in isolated guinea-pig ileum. The results demonstrate that pretreatment
      of animals with the plant flavonoid (25 and 50 mg/kg, i.p.) produces a
      significant inhibition of gastric lesions induced by ethanol but not those
      induced by restraint stress or indomethacin and suggest a probable involvement of
      a prostaglandins-independent mechanism of gastroprotection. At similar doses,
      both the intestinal transit as well as the accumulation of intestinal fluids
      induced by castor oil in mice were significantly inhibited by ternatin.
      Furthermore, the flavonoid antagonised the contractile responses evoked by
      different agonists on guinea-pig ileum in vitro and its inhibitory potential for
      the drugs are in the order of acetylcholine > histamine > serotonin > barium
      chloride. Taken together, these results point out a possible antidiarrhoeal
      effect of ternatin since inhibition of intestinal motility and secretion can
      greatly control clinical diarrhoea.

PMID- 9140230
TI  - In vitro formation of crocetin glucosyl esters by Crocus sativus callus extract.
AB  - Callus extracts of Crocus sativus exhibited the ability to transform all-trans
      crocetin into its related glycosides between pH 7.0 and 7.6 in the presence of
      uridine-diphospho-glucose. The reactions involved the step-wise addition of a
      glucose moiety to a free carboxyl function and the 1-->6 addition of a glucose
      moiety to a glucosyl ester function. The kinetics of synthesis for each glycoside
      seemed to indicate that two distinct glucosyl transferases were implicated in the
      synthesis of crocin, all-trans-crocetin di-(beta-D-gentiobiosyl) ester.

PMID- 9140231
TI  - New aporphine alkaloids and cytotoxic constituents of Hernandia nymphaeifolia.
AB  - Two new aporphine alkaloids, (+)-N-hydroxyhernangerine (1) and N
      formyldehydroovigerine (2) as minor bases, along with four known aporphines, (+)
      magnoflorine, (+)-hernovine, (+)-N-methylhernovine, and (+)-laurotetanine, two
      known isoquinolones, thalifoline and northalifoline, and one benzylisoquinoline,
      (+)-reticuline, have been additionally isolated from the trunk bark of Hernandia
      nymphaeifolia. The structures of these compounds were elucidated by spectroscopic
      evidence. Six of the isolated compounds show significant cytotoxic activities
      (ED50 values < 1 microgram/ml) against P-388, KB16, A549, or HT-29 cell lines.

PMID- 9140232
TI  - Konishiol, a new sesquiterpene, and bioactive components from Cunninghamia
      konishii.
AB  - Three sesquiterpenes, konishiol (1), cadalenol (2), 3-cedranol (3), one
      diterpene, manool (4), and one lignan, (+)-tsugacetal (5), have been isolated,
      for the first time, from the whole plant of Cunninghamia konishii by using
      bioactivity-directed fractionation. Compound 1 is new to the literature, and its
      chemical structure was determined by various spectroscopic analyses including
      EIMS, HREIMS, NOE, NOESY, and by preparing its di-acetyl derivative (1a).
      Compounds 2-5 showed moderate to weak bioactivities in brine shrimp (BST) and
      mosquito larvae (YFM) bioassays as well as cytotoxicities against three human
      solid tumor cell lines.

PMID- 9140233
TI  - Triterpene saponins from Cyclamen coum var. coum.
AB  - From the tubers of Cyclamen coum (Primulaceae) three new saponins, cyclaminorin
      (1), cyclacoumin (3) and mirabilin lactone (4) were isolated together with a
      known saponin, deglucocyclamin (2). The structures of the new compounds were
      established as 13 beta,28-epoxy-3 beta-(([beta-D-glucopyranosyl-(1-->2)]- [beta-D
      glucopyranosyl-(1-->4)]-alpha-L-arabinopyranosyl) oxy) 16 alpha-hydroxy-olean-30
      al (1), 13 beta,28-epoxy-3 beta-((([beta-D-xylopyranosyl-(1-->2) -beta-D
      glucopyranosyl-(1-->4)]-[beta-D-glucopyranosyl-(1-->2)]- alpha-L
      arabinopyranosyl)oxy)-16 alpha,23-dihydroxy-olean-30-al (3) and 16 alpha-hydroxy
      3 beta-((([beta-D-xylopyranosyl-(1-->2)]- [beta-D-glucopyranosyl-1-->6)]-beta D
      glucopyranosyl-(1-->4))- [beta-D-glucopyranosyl-(1-->2)]-alpha-L
      arabinopyranosyl)-oxy) olean-12-eno-30,28-lactone (4). Structure elucidattions
      were accomplished using both spectral (NMR, MS, IR) and chemical methods.

PMID- 9140234
TI  - An analytical study, anti-inflammatory and analgesic effects of Harpagophytum
      procumbens and Harpagophytum zeyheri.
AB  - The iridoids of Harpagophytum procumbens and Harpagophytum zeyheri were studied
      by CLHP. Harpagoside is the main iridoid for both drugs whereas 8-p
      coumaroylharpagide is a representative iridoid of Harpagophytum zeyheri only. The
      ratio harpagoside/8-p-coumaroylharpagide can be used to distinguish chemically
      both species. For commercial dried aqueous extracts this ratio is intermediate
      because they are probably prepared from a mixture of H. procumbens and H. zeyheri
      drugs. The aqueous extracts of both drugs show similar analgesic and anti
      inflammatory properties. Harpagophytum procumbens and Harpagophytum zeyheri
      should be accepted as sources for the drug Harpagophyti radix.

PMID- 9140235
TI  - Chemical and antibacterial studies of two Helichrysum species of Greek origin.
AB  - The chemical composition of the essential oils obtained from the aerial parts of
      Helichrysum stoechas ssp. barrelieri and H. taenari was analysed by GC and GC/MS.
      From the thirty-nine identified constituents representing the 73.87% and 87.41%
      of the two oils, respectively, beta-elemene, beta-caryophyllene, geraniol, and
      camphene were the major components. Furthermore, it was found that the oils
      exhibited significant antibacterial activity against six Gram (+/-) bacteria.

PMID- 9140236
TI  - Cycloartane triterpene glycosides from the roots of Astragalus melanophrurius.
AB  - From the roots of Astragalus melanophrurius eight known saponins (1-8) were
      isolated. Based on spectral data (IR, 1H- and 13C-NMR, and FABMS), the structures
      were established as astrasieversianins II (1) and X (4), astragalosides I (2), II
      (3), IV (5) and VI (7), and cyclocanthosides E (6) and G (8). The isolates were
      evaluated in a broad range of bioassay systems and found to be inactive. Modest
      antibacterial activity was observed, however, as was immunomodulatory activity,
      as indicated by stimulation of isolated human lymphocytes.

PMID- 9140237
TI  - Bufadienolides and other constituents of Urginea sanguinea.
AB  - Fresh bulbs of Urginea sanguinea yielded stigmasterol, phloroglucinol,
      phloroglucinol 1-beta-D-glucopyranoside (phlorin), scillaren A, a novel compound
      5 alpha-4,5-dihydroscillaren A (1), salicylic acid, and 3-hydroxy-4-methylbenzoic
      acid. The latter two showed weak antibacterial activity. The compounds were
      identified using spectroscopic techniques such as 1D and 2D NMR, EI-MS and FAB
      MS.

PMID- 9140238
TI  - Practice guideline for the treatment of patients with Alzheimer's disease and
      other dementias of late life. American Psychiatric Association.

PMID- 9140239
TI  - Effect of duration from symptom onset on the negative predictive value of a
      normal ECG for exclusion of acute myocardial infarction.
AB  - STUDY OBJECTIVE: We hypothesized that the negative predictive value of the ECG
      would improve with time and assessed the effect of time elapsed from symptom
      onset to ED presentation on the negative predictive value, sensitivity,
      specificity, and positive predictive value of the initial ECG in patients
      presenting with symptoms suggestive of acute myocardial infarction (AMI).
      METHODS: We conducted a cross-sectional study in a university teaching hospital.
      Our structured data instrument, completed at the time of presentation included
      demographics, time of onset of symptoms, history, laboratory, and ECG findings.
      AMI was diagnosed with the use of international diagnostic criteria. Patients
      were stratified according to duration of time from symptom onset at 3-hour
      intervals. RESULTS: We enrolled 526 patients in the study group. The mean age was
      59 years; 40% were female. The mean time elapsed from symptom onset to
      presentation was 185 minutes. A diagnosis of AMI was made in 104 patients (20%).
      The negative predictive values of a normal ECG for exclusion of AMI, stratified
      by duration of time from symptom onset, were: 0 to 3 hours, 93.2% (95% confidence
      interval [CI], 87.4% to 96.1%); 3 to 6 hours, 93.0% (95% CI, 83.0% to 98.1%); 6
      to 9 hours, 92.6% (95% CI, 75.8% to 99.1%); and 9 to 12 hours, 94.1% (95% CI,
      71.3% to 99.9%) (P = 1.0). The sensitivity, specificity, and positive predictive
      value of the ECG were similar in all groups. CONCLUSION: The negative predictive
      value of a normal ECG for exclusion of AMI does not improve as the duration of
      time from symptom onset to presentation increases. Normal ECG findings cannot be
      used to rule out an AMI, even those obtained up to 12 hours after symptom onset.

PMID- 9140240
TI  - Selective aortic arch perfusion during cardiac arrest: enhanced resuscitation
      using oxygenated perflubron emulsion, with and without aortic arch epinephrine.
AB  - STUDY OBJECTIVE: To evaluate selective aortic arch perfusion (SAAP) with an
      oxygenated fluorocarbon emulsion, with and without aortic arch epinephrine during
      cardiac arrest. METHODS: This randomized, controlled study, undertaken at a
      university research laboratory, involved 15 mixed-breed dogs. After 10 minutes of
      ventricular fibrillation and 30 seconds of CPR, the dogs were randomized to three
      groups, each comprising five dogs. Group 1 (controls) dogs were given CPR and
      intravenous epinephrine, .01 mg/kg, at 10.5 minutes and then every 3 minutes.
      Group 2 dogs (IVE-SAAP) were treated with CPR and intravenous epinephrine (IVE)
      in the same fashion as the control group but were also subjected to SAAP with 275
      mL of oxygenated 60% wt/vol perflubron emulsion over 30 seconds. Group 3 dogs
      (AoE-SAAP) received the same treatment as the IVE-SAAP group, except that the
      first epinephrine dose was given intraaortically. RESULTS: Coronary perfusion
      pressure (CPP) increased during SAAP in both the IVE-SAAP and AoE-SAAP groups but
      was greater in the AoE-SAAP group. CPR diastolic CPP after SAAP was significantly
      greater in the AoE-SAAP group than in the control group. Return of spontaneous
      circulation (ROSC) occurred in two control dogs, all five IVE-SAAP dogs, and all
      five AoE-SAAP dogs. The time elapsed from the initiation of CPR to ROSC was 6.1
      +/- 1.9 minutes in the AoE-SAAP group, compared with 11.0 +/- 5.8 minutes in the
      IVE-SAAP group. CONCLUSION: SAAP with oxygenated perflubron emulsion improved
      ROSC, both with and without aortic arch epinephrine. The combination of SAAP with
      perflubron emulsion and aortic arch epinephrine resulted in higher CPP and more
      rapid ROSC.

PMID- 9140241
TI  - Effect of electrode position and gel-application technique on predicted
      transcardiac current during transthoracic defibrillation.
AB  - STUDY OBJECTIVE: In transthoracic defibrillation, the American Heart Association
      (AHA) recommends wide separation of electrodes and avoidance of gel smearing
      between electrodes. Few data support this recommendation. Our objective was to
      determine the importance of electrode placement and gel-application technique on
      transcardiac defibrillation current and the effect of changes caused by
      postexercise vasodilation and sweating. METHODS: Our subjects were 10 normal
      adults, 5 men and 5 women, who ranged in age from 22 to 48 years. We determined
      interelectrode impedance (Z) using a validated test-pulse method that does not
      require shock delivery. Electrode placement/gel-application techniques were
      varied among four types: (1) AHA-recommended technique (apex-to-anterior
      electrode placement, no smearing of gel between electrodes); (2) parasternal-to
      anterior placement, electrodes within 2 cm of each other, no smearing of gel
      between electrodes; (3) parasternal-to-anterior placement, electrodes within 2 cm
      of each other with smearing of gel between electrodes (worst-case scenario); and
      (4) apex-to-anterior placement, smearing of gel between electrodes. To assess the
      effect of cutaneous vasodilation and sweating on interelectrode impedance, we
      repeated these measurements after the subjects performed 12 to 18 minutes of
      treadmill exercise. The ratio of predicted transcardiac current of the AHA
      technique to that of the nonstandard technique was estimated with this formula:
      square root of Z, non-standard technique divided by square root of Z, AHA
      technique. RESULTS: Resting interelectrode impedance declined 38% from 58 +/-
      10.3 omega (AHA-recommended technique) to 36 +/- 7.6 omega (electrode paddles
      adjacent, gel smeared between) (P < .01). Predicted transcardiac current ratio
      was reduced to .78 +/- .09 (P < .01), a 22% reduction. We noted no change in the
      results after exercise. CONCLUSION: Adjacent placement of electrodes and smearing
      of gel between electrodes creates a low-impedance pathway along the chest wall,
      which shunts current away from the heart. Thus improper application of electrodes
      and gel substantially degrades transcardiac current and may result in failed
      defibrillation. Sweating and vasodilation did not cause a similar problem.

PMID- 9140242
TI  - Clinical course of crack cocaine body stuffers.
AB  - STUDY OBJECTIVE: To describe the clinical course of a cohort of patients
      presenting to the emergency department with acute crack cocaine body-stuffer
      syndrome. METHODS: We conducted a retrospective cohort study in the ED of a
      county hospital with 75,000 visits per year. Our study cohort comprised all
      patients who presented between January 1993 and April 1995 and who met the
      definition of a crack cocaine body stuffer. We defined a crack cocaine body
      stuffer as anyone who admitted to or was strongly suspected of ingesting crack
      cocaine as a means of escaping detection by authorities, not for recreational
      purposes or as a means of transporting the drug across borders. RESULTS: We
      identified 98 cases; most such patients were brought to the ED by law enforcement
      agents. Most were male and younger than 30 years. Self-report by patients
      indicated that the amount of crack cocaine ingested ranged from 1 to more than 15
      rocks. Most commonly the drug was unwrapped (28%) or wrapped in a plastic
      sandwich bag (29%). Generalized seizures developed in 4% of the patients; in all
      these patients seizures occurred within 2 hours of ingestion. In no patient did
      dysrhythmias develop. Many patients had minor signs of cocaine intoxication: 54%
      were tachycardic, 23% were hypertensive, 22% were agitated, and 19% required
      sedation. CONCLUSION: Mild cocaine intoxication is common in crack cocaine body
      stuffers, with seizures occurring within 2 hours of ingestion in a small
      percentage of patients.

PMID- 9140243
TI  - Transcutaneous pacing in a hypothermic-dog model.
AB  - STUDY OBJECTIVE: To evaluate the hemodynamic response to transcutaneous pacing
      (TCP) during rewarming from hypothermia. METHODS: We conducted a prospective,
      controlled laboratory investigation using 20 mongrel dogs. The animals were
      anesthetized, intubated, and mechanically ventilated. Arterial pressure, core
      temperature, and cardiac rhythm were continuously monitored. All dogs were cooled
      to a core temperature of 27 degrees C; experimental animals were then subjected
      to TCP with active rewarming, and control animals underwent sham transcutaneous
      pacing and rewarmed in the same manner. Serial hemodynamic measurements, time to
      rewarming, and cardiac isoenzyme concentrations were analyzed. RESULTS: Rewarming
      was accomplished significantly faster in the paced group (171.5 +/- 31.5 minutes)
      than in the control group (254 +/- 55.9 minutes, P < .05). After rewarming, the
      mean cardiac index in the paced dogs returned to 84% of baseline, compared with
      63% of baseline in the nonpaced group (P < .05). None of the paced animals
      demonstrated significant hemodynamic deterioration, potentially lethal
      arrhythmias, or other evidence of myocardial injury. CONCLUSION: TCP is safe,
      effective and easily implemented in dogs. In this small series of dogs, TCP
      restored and maintained hemodynamic stability and allowed the hypothermic animals
      to rewarm in half the time required by their nonpaced counterparts.

PMID- 9140244
TI  - Effects of simulated mouth-to-mouth ventilation during external cardiac
      compression or active compression-decompression in a swine model of witnessed
      cardiac arrest.
AB  - STUDY OBJECTIVE: To assess the effects of simulated mouth-to-mouth (MTM)
      ventilation on blood gases, gas exchange, and minute ventilation during external
      cardiac compression (ECC) or active compression-decompression (ACD) in a swine
      model of witnessed cardiac arrest and bystander CPR. METHODS: Twenty swine were
      anesthetized, intubated, ventilated with room air, and monitored for aortic and
      right atrial pressure and blood gas sampling. After 1 minute of ventricular
      fibrillation cardiac arrest, ECC or ACD was manually performed at a rate of 100
      per minute for 12 minutes. Animals in the room air group had their endotracheal
      tubes open to air, whereas those in the MTM group were mechanically ventilated
      with a gas mixture of 16% oxygen and 4% carbon dioxide. Arterial and venous PO2,
      PCO2, and pH values; oxygen consumption (VO2); carbon dioxide production (VCO2);
      and minute ventilation (VE) were measured at baseline and 1, 5, 9, and 13 minutes
      after induction of cardiac arrest. RESULTS: MTM ventilation did not alter
      arterial or venous PO2 values in comparison with room air but did result in
      higher arterial PCO2 values at 5 and 9 minutes (although the mean PCO2 was 40 mm
      Hg or less [5.3 kPa] in all groups) and significant central venous hypercarbic
      acidosis at 9 and 13 minutes. Arterial PO2 values were greater in the ACD than
      the ECC groups at 5, 9, and 13 minutes, although all groups maintained acceptable
      PO2 (mean values > or = 60 mm Hg [8.0 kPa]) through 9 minutes of CPR and through
      13 minutes in all but the ECC-room air group. PCO2 values were lower in the ACD
      groups beyond 1 minute, with the ACD-room air group showing extreme
      hyperventilation (mean PCO2 < or = 20 mm Hg [2.7 kPa]). MTM ventilation resulted
      in negative VO2 and VCO2 for the first few minutes, reflecting changes in
      pulmonary gas stores. As equilibrium was approached, VO2 and VCO2 approached zero
      in all groups, reflecting low cardiac output. MTM ventilation did not improve VE
      over room air at any time during ACD. It did improve VE during ECC, but only at
      the 12th interval. CONCLUSION: In this swine model of witnessed CPR, simulated
      MTM ventilation was not beneficial for blood gases, gas exchange, or ventilation
      during ECC or ACD CPR.

PMID- 9140245
TI  - Longitudinal study of emergency physicians by the American Board of Emergency
      Medicine: 1995 interim survey results.
AB  - STUDY OBJECTIVE: To obtain current demographic data and information regarding the
      opinion of a stratified random sample of emergency physicians about the greatest
      current challenges facing emergency medicine. METHODS: An annual survey was
      conducted by the American Board of Emergency Medicine (ABEM) using a stratified
      random sample of 1,004 emergency physicians selected from four cohorts, 1979,
      1984, 1988, and 1993. These samples were further divided between diplomates who
      had completed emergency medicine residency training and those who had not. The
      1993 non-residency-trained panel was replaced by a random sample of American
      College of Emergency Physicians members who were full-time emergency physicians,
      were not ABEM diplomates, and had not completed a residency in emergency
      medicine. The interim survey instrument is a one-page collection of relevant
      demographic items selected from the comprehensive 5-year questionnaire with the
      addition of the open-ended question, "What are the greatest challenges facing
      emergency medicine today?" RESULTS: Of the interim surveys distributed, 95% (n =
      956) were returned. Because the 1995 interim survey was the first distributed
      after the initial 1994 comprehensive survey, the demographic data had changed
      little. Such data will become increasingly important and useful as changes are
      reported over subsequent years. The main challenge identified by participants was
      the impact of managed care (31%), followed by economic and financial issues
      (23%). Personal impact issues, such as individual stress and malpractice,
      accounted for a smaller number of responses (18%). CONCLUSION: Overall, the ABEM
      Longitudinal Study participant responses to the 1995 interim survey describe a
      committed group of emergency physicians who are struggling and coping with the
      needs of a maturing specialty and with the crosscurrents and changes in American
      medicine.

PMID- 9140246
TI  - Attitudes toward the use of a metal detector in an urban emergency department.
AB  - STUDY OBJECTIVE: To determine the attitudes of patients, their family and
      friends, and ED staff toward a walk-through metal detector in the ED. METHODS: We
      conducted a survey of a convenience sample of ED patrons (patients and their
      friends and family) and staff at a university-affiliated Level I trauma center.
      RESULTS: We surveyed 176 patrons and 95 employees (35 nurses, 30 physicians, 16
      security officers, and 14 staff members). Overall, 80% of the patrons and 85% of
      the employees said they liked the metal detector. Eighty-nine percent of the
      patrons and 73% of the employees said the metal detector made them feel safer.
      Only 12% of the patrons and 10% of the employees said the metal detector invaded
      their privacy or the privacy of others. Fewer than 1% of the patrons said they
      were less likely to return to our ED because of the metal detector, and 39% said
      it made them more likely to return. We detected no significant differences with
      regard to age, sex, or race. CONCLUSION: Most patrons and staff liked the metal
      detector and said it created a safer ED environment. Only a few disliked the
      presence of the metal detector or said it invaded their privacy. Institutions
      concerned about their employees' and patrons' perceptions of safety should
      consider installing metal detectors in their EDs.

PMID- 9140247
TI  - Observational evaluation of compliance with traffic regulations among helmeted
      and nonhelmeted bicyclists.
AB  - STUDY OBJECTIVE: To evaluate whether helmeted bicyclists are more compliant with
      traffic regulations than nonhelmeted bicyclists. METHODS: This prospective
      observational study, using a convenience sample, was conducted during daylight
      hours at three separate intersections, marked with legal stop signs, near the
      campus of a major university. Data collected included helmet use, legal hand
      signal use to indicate a turn or stop, and whether the bicyclist came to a
      complete stop before proceeding through the intersection. RESULTS: A total of
      1,793 bicyclists were evaluated. Only 8.8% of the bicycle riders were wearing
      helmets. Helmeted bicyclists were 2.6 times more likely than nonhelmeted
      bicyclists to make legal stops (P < .000001; odds ratio [OR], 3.1; 95% confidence
      interval [CI], 2.1 to 4.6). They were also 7.1 times more likely to use hand
      signals (P < .000001; OR, 7.2; 95% CI, 2.8 to 18.2). CONCLUSION: Helmeted bicycle
      riders showed a significantly greater compliance with two traffic laws than
      nonhelmeted bicyclists. They were 2.6 times more likely to stop at stop signs and
      7.1 times more likely to use legal hand signals. This very strong association of
      helmet use with safer riding habits has implications for injury-control efforts
      aimed at preventing bicycle-related injuries.

PMID- 9140248
TI  - Estimates of injury impairment after acute traumatic injury in motorcycle crashes
      before and after passage of a mandatory helmet use law.
AB  - STUDY OBJECTIVE: This study estimates trends in impairment before and after the
      1992 California Mandatory Helmet Use Law using the injury impairment Scale (IIS).
      METHODS: We linked medical records and police reports for a cohort of 4,790
      nonfatally injured motorcycle riders who crashed between January 1, 1991, and
      December 31, 1993, and were treated for injuries in 1 of 18 hospitals in 10
      California counties. All injuries were coded according to the Abbreviated Injury
      Scale and matched to corresponding codes in the IIS. The IIS provides an estimate
      of the likelihood of impairment from any given injury. Impairment is not directly
      measured. RESULTS: After implementation of the law, the proportion of riders
      likely to sustain head injury-related impairments decreased by 34.1%. Impairments
      resulting from head injuries were the most common type before passage of the law,
      but they were surpassed by leg injury-related impairments after passage. Helmet
      nonuse, speeding, and drinking were among variables associated with increased
      odds ratios of head injury estimated to cause impairment. CONCLUSION: The
      proportion of motorcycle riders with head injury impairment as estimated with the
      IIS decreased significantly after the introduction of mandatory motorcycle helmet
      legislation.

PMID- 9140249
TI  - Law enforcement K-9 dog bites: injuries, complications, and trends.
AB  - STUDY OBJECTIVE: To quantify the number of individuals bitten, the number of
      bites per patient, and the types of injuries and complications caused by law
      enforcement K-9 dog bites treated in the Jail Ward Emergency Department of the
      Los Angeles County-University of Southern California Medical Center. These
      variables were compared before and after a change in K-9 police policy from the
      "bite-and-hold" to the "find-and-bark" technique or stricter controls were
      instituted over the K-9 teams. METHODS: A retrospective chart review of all
      patients in police custody with K-9 dog bites who presented to the Jail Ward ED
      between January 1, 1988, and December 31, 1995, was conducted. Demographic data
      of patients with K-9 dog bites, the number and location of bites, complications,
      procedures performed, and management of bites were recorded and compared between
      the periods 1988-1991 (before the policy changes) and 1992-1995 (after the
      changes). RESULTS: Between 1988 and 1995 790 in-custody patients were treated for
      K-9 dog bites in the Jail Ward ED; 705 charts were available for review. Nearly
      all the patients (98.6%) were male, with a mean age of 25; 85.0% were Hispanic or
      black. More than half (57.2%) sustained three or more bites, mainly to the
      extremities. Complications ensued in 19.3%: vascular in 7.0%, infection in 5.0%,
      fracture or cortical violation in 4.0%, nerve injury in 1.9%, and tendon injury
      in 1.1%. Half (49.9%) were hospitalized, with a median stay of 3 days. After the
      change in K-9 policy, the number of patients with K-9 dogs bites presenting to
      the Jail Ward ED decreased from 639 (1988-1991) to 66 (1992-1995). The proportion
      of patients who sustained three or more bites decreased from 58.4% to 45.5%. The
      rate of vascular complications decreased from 7.5% to 1.6%, the rate of fractures
      decreased from 2.4% to 0, and the rate of cortical violations increased from 1.4%
      to 6.3%. The proportion of patients hospitalized decreased from 52.0% to 33.8%.
      CONCLUSION: K-9 dog bites are associated with significant injuries and
      complications. In this study, changes in law enforcement K-9 policy contributed
      to a significant decrease in the overall number of individuals bitten, the number
      of injuries and complications, and the proportion of patients hospitalized.

PMID- 9140250
TI  - Helmets work best.

PMID- 9140251
TI  - Outbreaks of Escherichia coli O157:H7 infection associated with drinking
      unpasteurized apple cider--October 1996. Update on emerging infections from the
      Centers for Disease Control and Prevention.

PMID- 9140252
TI  - Recommended guidelines for reviewing, reporting, and conducting research on in
      hospital resuscitation: the in-hospital "Utstein style". American Heart
      Association.

PMID- 9140253
TI  - Flecainide overdose: is cardiopulmonary support the treatment?
AB  - Flecainide toxicity can impair cardiac function and precipitate circulatory
      collapse, which in turn depresses clearance and redistribution of flecainide.
      Treatment directed at improving cardiac function is often ineffective in the
      presence of persistently increased flecainide levels. We report a novel approach
      to severe flecainide overdose using peripheral cardiopulmonary bypass support
      (CBS) to maintain perfusion of the liver, thereby allowing clearance of the drug.
      CBS was initiated to resuscitate a young woman who had ingested flecainide in a
      suicide attempt. The patient had an agonal rhythm, no effective blood pressure,
      and a flecainide level of 5.4 micrograms/mL (therapeutic range, .2 to 1.0
      microgram/mL). During 10 hours of CBS, the flecainide level decreased to 1.4
      micrograms/mL, a half-life of 6 hours. Effective cardiac rhythm and blood
      pressure returned. CBS successfully supported this patient until the flecainide
      level decreased as a result of redistribution and normal clearance mechanisms.
      Unfortunately, because of severe neurologic damage sustained at the time of
      overdose, the patient died 4 days after admission.

PMID- 9140254
TI  - Descending necrotizing mediastinitis: complication of a simple dental infection.
AB  - Descending necrotizing mediastinitis (DNM) is a rare complication of periodontic
      infection. The delay in diagnosis of DNM is believed to contribute to its high
      mortality rate. We report the case of a healthy 23-year-old man who was seen in
      the urgent care center, given the diagnosis of dental infection, prescribed
      penicillin, and sent home. He returned 48 hours later complaining of myalgias,
      purulent drainage from around his teeth, chest pain, and dyspnea. DNM was
      diagnosed, and aggressive treatment comprising thoracotomy, cervical incision and
      drainage, and antibiotics was begun. The patient responded well to treatment and
      was discharged from the hospital on postoperative day 20. Prompt diagnosis and
      immediate therapy are imperative for this rare condition.

PMID- 9140255
TI  - Acute upper-airway obstruction in a patient with achalasia.
AB  - The most common presenting symptoms of achalasia are dysphagia, recurrent
      regurgitation, and gradual weight loss. Surprisingly, many achalasia patients
      tolerate considerable esophageal distention without complaint. In very few cases
      is respiratory distress the only presenting symptom of achalasia. We describe
      such a case.

PMID- 9140256
TI  - One pinch.

PMID- 9140257
TI  - Anesthesia for fish envenomation.

PMID- 9140258
TI  - Rectal temperature in marathon runners.

PMID- 9140259
TI  - Optimal positioning for cervical immobilization.

PMID- 9140260
TI  - Digoxin, hyperkalemia, and kidney failure.

PMID- 9140261
TI  - Digoxin, hyperkalemia, and kidney failure.

PMID- 9140262
TI  - Digoxin, hyperkalemia, and kidney failure.

PMID- 9140263
TI  - Clinical policy for the initial approach to patients presenting with a chief
      complaint of seizure who are not in status epilepticus. American College of
      Emergency Physicians.

PMID- 9140264
TI  - Anxiety-induced hyperventilation. A common cause of symptoms in patients with
      hypertension.

PMID- 9140266
TI  - Triglycerides and coronary risk in women and the elderly.
AB  - There seems little doubt that triglycerides are causally related to the progress
      of atherogenesis. Mechanisms for this effect include adverse quantitative and
      qualitative changes in circulating lipoproteins. In particular, the effects of
      lower high-density lipoprotein levels and the production by hypertriglyceridemia
      of small, dense low-density lipoproteins are of great significance. The role of
      triglyceride-rich remnant particles in atherogenesis is likely important. These
      remnants, which are lipoproteins rich in both cholesterol and triglycerides, can
      be shown to produce cholesteryl ester-laden macrophages in vitro and are probably
      atherogenic in vivo. Triglyceride levels are a significant risk factor for
      coronary artery disease in women, more so than in men. Triglyceride levels also
      increase in older patients and continue to be predictors of coronary risk in both
      men and women older than 65 years. It is unclear whether triglyceride
      intervention efforts should be directed at lowering triglyceride levels (such as
      is accomplished with niacin or fibric acid derivatives) or lowering low-density
      lipoprotein levels in patients with high triglyceride levels, assuming
      triglyceride levels are only a passive marker of atherosclerotic risk. Until more
      is known about the precise role of hypertriglyceridemia in atherogenesis in women
      and older patients, use of triglyceride-lowering drugs should be conservative and
      limited to those individuals with high triglyceride levels (> 4.5 mmol/L [> 400
      mg/dL]) who do not respond to diet modifications and who are at risk of coronary
      disease either because of a history of vascular disease or the presence of other
      risk factors.

PMID- 9140265
TI  - Human immunodeficiency virus type 1 protease inhibitors.
AB  - Until recently, treatment for human immunodeficiency virus type 1 (HIV-1)
      infection was limited to the use of nucleoside inhibitors of the viral enzyme
      reverse transcriptase. While these agents initially offered promise, they have
      only modest antiviral activity and the benefits of treatment are limited by the
      emergence of drug resistance and dose-limiting toxic effects. Development of more
      potent drugs that target different stages of the virus life cycle has thus been
      aggressively pursued. Efforts to develop inhibitors of HIV-1 protease have
      yielded a potent new class of compounds that suppress HIV-1 replication to an
      extent far greater than was previously attainable. Four protease inhibitors,
      saquinavir mesylate, ritonavir, nelfinavir, and indinavir sulfate, have been
      approved by the Food and Drug Administration. Other agents are undergoing active
      investigation. The purpose of this article is to review the currently available
      data on those agents that have been approved for clinical use.

PMID- 9140267
TI  - Screening for colorectal cancer. A comparison of 3 fecal occult blood tests.
AB  - BACKGROUND: Colorectal cancer is the second leading cause of cancer deaths in the
      United States. Fecal occult blood testing has become a standard screening test
      for large-bowel cancers in the average asymptomatic population. Performance
      characteristics of the test and physician and participant compliance are the 2
      major elements that impact the success of screening and early detection.
      OBJECTIVES: To evaluate the nonhydrated Hemoccult, rehydrated Hemoccult, and
      Hemoccult SENSA tests (SmithKline Diagnostics Inc, Palo Alto, Calif) and to
      assess participant and physician compliance. METHODS: A mass community-based
      screening study in an urban setting. Kits were distributed by a local pharmacy
      and at community sites. Diagnostic tests were completed through physicians'
      offices and clinics. Participants were asymptomatic and aged 50 years or older.
      Those who tested positive were advised to follow up with a physician. RESULTS: An
      overall positivity rate of 16% was reported for the 8293 kits that were
      processed. Rehydrated Hemoccult had a positivity rate of 15%; Hemoccult SENSA,
      7%; and nonhydrated Hemoccult, 5%. The positive predictive value of nonhydrated
      Hemoccult was 14%; rehydrated Hemoccult, 7%; and Hemoccult SENSA, 11%. Of those
      who tested positive, 59% had a colonoscopy or flexible sigmoidoscopy and double
      contrast barium enema examination on follow-up. Recommended follow-up was more
      frequent for those who consulted a gastroenterologist. CONCLUSIONS: Rehydrated
      Hemoccult yielded a higher positivity rate and lower positive predictive value
      than either Hemoccult SENSA or nonhydrated Hemoccult. Hemoccult SENSA approached
      the positive predictive value of nonhydrated Hemoccult. Adequacy of follow-up of
      patients testing positive for fecal occult blood needs improvement.

PMID- 9140268
TI  - Atrial fibrillation and stroke prevention with warfarin in the long-term care
      setting.
AB  - BACKGROUND: While the benefits of warfarin sodium therapy for stroke prevention
      in patients with atrial fibrillation (AF) have been extensively documented,
      generalizing clinical trial results to the majority of elderly persons with AF,
      especially to those who reside in the long-term care setting, remains
      challenging. OBJECTIVES: To determine the prevalence of AF in the
      institutionalized elderly population and the proportion receiving anticoagulation
      therapy with warfarin: to identify the clinical and functional characteristics of
      institutionalized elderly persons with AF that are associated with the use of
      warfarin; and to assess the quality of prescribing and monitoring of warfarin
      therapy in institutionalized elderly persons with AF. METHODS: This study
      involved 30 long-term care facilities (total No. of beds, 6437) located in New
      England, Quebec, and Ontario. The proportion of patients with AF who were
      receiving treatment with warfarin was determined. The association between
      clinical and functional characteristics and the use of warfarin was examined with
      crude and multivariable-adjusted analyses. For study subjects with at least 2
      weeks of warfarin therapy during the 12-month period preceding the date of
      medical record abstraction, we assessed the quality of warfarin prescribing based
      on all international normalized ratio or prothrombin time ratio values during
      this period. RESULTS: An electrocardiogram indicating AF was present in the
      records of 413 of 5500 long-term care residents (7.5%); 32% of such patients were
      being treated with warfarin. Only a history of stroke was found to be positively
      associated with the use of warfarin in this setting. Patients with a diagnosis of
      dementia and those in the oldest age group (> or = 85 years) were less likely to
      receive warfarin therapy. Warfarin was commonly prescribed to patients with a
      history of bleeding, substantial comorbidity and functional impairment, a history
      of falls, or concomitant potentiating drug therapy. Patients were maintained
      above or below the recommended therapeutic range 60% of the time. CONCLUSIONS:
      Atrial fibrillation is common in patients residing in long-term care facilities,
      but its management with warfarin is highly variable. A more systematic approach
      to decision making regarding the use of warfarin for stroke prevention in these
      patients is required. Among patients receiving warfarin, the quality of
      anticoagulation care warrants improvement.

PMID- 9140269
TI  - Primary care clinicians' performance for detecting actinic keratoses and skin
      cancer.
AB  - BACKGROUND: If skin cancer screening is to become widely adopted, its
      effectiveness depends on the ability of primary care clinicians to detect
      cutaneous malignancies. OBJECTIVE: To assess primary care clinicians' proficiency
      for detecting skin cancers and actinic keratoses in a clinic population. METHODS:
      A convenience sample of 190 white male patients aged 40 years or older presenting
      to a university-affiliated Veterans Affairs general internal medicine or
      dermatology clinic were included in the study. Each patient was independently
      examined by a primary care clinician and a dermatologist to measure interobserver
      agreement. We compared the ability of primary care clinicians to diagnose actinic
      keratoses and skin cancers using dermatologists' examinations as a pragmatic
      reference standard. RESULTS: Agreement was moderate as to whether a patient had
      single actinic keratosis (kappa, 0.36; 95% confidence interval [CI], 0.22-0.50),
      multiple actinic keratoses (kappa, 0.48; 95% CI, 0.34-0.61), or skin cancer
      (kappa, 0.48; 95% CI, 0.34-0.62). Agreement decreased when individual lesions
      were the unit of analysis. When the patient was the unit of analysis, primary
      care clinicians identified the presence of skin cancer with a sensitivity of 57%
      (95% CI, 44%-68%), specificity of 88% (95% CI, 81%-93%), positive likelihood
      ratio of 4.9 (95% CI, 3.0-8.3), and negative likelihood ratio of 0.48 (95% CI,
      0.35-0.63). When the lesion was the unit of analysis the sensitivity was 38% (95%
      CI, 29%-47%), the specificity was 95% (95% CI, 93%-96%), the positive likelihood
      ratio was 7.1 (95% CI, 4.8-10.3), and the negative likelihood ratio was 0.66 (95%
      CI, 0.56-0.75). CONCLUSIONS: Examinations performed by primary care clinicians
      for diagnosing skin cancer lacked sensitivity. Without improved diagnostic
      skills, primary care clinicians' examinations may be ineffective as a screening
      test.

PMID- 9140270
TI  - Diagnosis and treatment of Helicobacter pylori infection among California
      Medicare patients.
AB  - BACKGROUND: Antibiotic treatment of Helicobacter pylori infection in active
      peptic ulcer disease has been demonstrated to speed ulcer healing, reduce the
      risk of rebleeding, and prevent long-term recurrence. The objective of this study
      was to determine whether Medicare patients with peptic ulcer disease who are
      admitted to acute care hospitals are being tested or treated for H pylori
      infection as recommended by a National Institutes of Health consensus panel.
      METHODS: The study was designed as a retrospective medical records survey. From
      the Medicare National Claims History File, all persons 65 years and older
      admitted to California fee-for-service hospitals for peptic ulcer disease in 1994
      were identified. A random sample of 600 claims was selected for review. After
      exclusions, 524 patients were eligible for study. The main outcome measures were
      (1) the proportion of patients who were tested for H pylori infection by 1 of the
      5 available methods (histopathologic study, urease assay, microbiologic culture,
      serum antibody testing, or urea breath test) and (2) the proportion who were
      treated with antibiotics (amoxicillin, tetracycline, clarithromycin, or
      metronidazole) for H pylori infection. RESULTS: Thirty-nine percent of patients
      with peptic ulcer disease were tested for H pylori infection and 3% were treated
      empirically. Only 47% of the patients who had a positive diagnostic test result
      for H pylori were treated with antibiotics. CONCLUSION: Because diagnosis and
      treatment of H pylori infection has been demonstrated to improve outcomes and
      decrease expenses, the data indicate a substantial opportunity to improve the
      care of elderly Medicare patients with peptic ulcer disease.

PMID- 9140271
TI  - Physicians' survival predictions for patients with acute congestive heart
      failure.
AB  - BACKGROUND: Current guidelines suggest that patients with low likelihoods of
      survival may be excluded from intensive care. Patients with new or exacerbated
      congestive heart failure are frequently but not inevitably admitted to critical
      care units. OBJECTIVE: To assess how well physicians could predict the
      probability of survival for acutely ill patients with congestive heart failure,
      and in particular how well they could identify patients with small chances of
      survival. METHODS: This was a prospective cohort study done in the emergency
      departments of a university hospital, a Veterans Affairs medical center, and a
      community hospital. The study population was consecutive adults for whom new or
      exacerbated congestive heart failure, diagnosed clinically, was a major reason
      for the emergency department visit. Physicians caring for the study patients in
      the emergency departments recorded their judgments of the numeric probability
      that each patient would survive for 90 days and for 1 year. The patients vital
      status at 90 days and 1 year was ascertained by multiple means, including
      interview, chart review, and review of hospital and state databases. RESULTS: By
      calibration curve analysis, the physicians underestimated survival probability at
      both 90 days and 1 year, particularly for patients they judged to have the lowest
      probabilities of survival. Their predictions had modest discriminating ability
      (receiver operating characteristic curve areas, 0.66 [SE = 0.020] for 90 days;
      0.63 [SE = 0.017] for 1 year). The physicians identified only 15 patients they
      judged to have a 90-day survival probability of 10% or less, whose survival rate
      was actually 33.3%. CONCLUSIONS: Physicians have great difficulty predicting
      survival for patients with acute congestive heart failure and cannot identify
      patients with poor chances of survival. Current triage guidelines that suggest
      patients with poor chances of survival may be excluded from critical care may be
      impractical or harmful.

PMID- 9140273
TI  - Hypocalcemia and skeletal disease as presenting features of celiac disease.
AB  - OBJECTIVE: To describe 15 patients examined for hypocalcemia, skeletal disease,
      or both in whom the diagnosis of celiac disease was subsequently made. DESIGN:
      Observational case series. PATIENTS: Fifteen patients (7 women and 8 men) were
      examined for hypocalcemia (n = 11), skeletal disease (n = 3), or both (n = 1).
      The diagnosis of celiac disease was subsequently made. The mean age of the
      patients was 62 years, and 11 patients were 60 years of age or older. RESULTS:
      Four patients had no gastrointestinal symptoms, 7 patients had mild or
      intermittent gastrointestinal symptoms, and 4 patients had persistent diarrhea.
      Ten patients had experienced weight loss. The serum total alkaline phosphatase
      level was elevated in 10 of 15 patients, the parathyroid hormone level was
      elevated in all patients, and the urinary calcium level was low in all 6 of the
      patients tested. The level of 25-hydroxyvitamin D was frankly low in 4 patients,
      marginal in 8 patients, and normal in 3 patients. Bone mineral density was
      reduced in all 8 patients in whom it was measured. CONCLUSIONS: Celiac disease
      should be considered in patients with unexplained metabolic bone disease or
      hypocalcemia, especially because gastrointestinal symptoms may be absent or mild.
      Advanced age does not exclude the diagnosis of celiac disease.

PMID- 9140272
TI  - Clinical adrenal insufficiency in patients receiving megestrol therapy.
AB  - OBJECTIVE: To describe the clinical and biochemical features of patients in whom
      adrenal insufficiency developed during megestrol acetate therapy for advanced
      breast cancer. PATIENTS AND METHODS: Thirteen patients with advanced breast
      cancer treated with oral megestrol acetate, 160 mg/d. RESULTS: Fatigue and
      weakness were observed in all 13 patients. Hypotension was observed in 8.
      Anorexia, nausea, vomiting, and diarrhea were observed in 3. Mean basal cortisol
      level at the time of symptoms was 41.4 nmol/L (range, 27.6-110.4 nmol/L). After
      corticotropin stimulation, mean cortisol level at 30 minutes was 239.2 nmol/L
      (range, 93.8-447.0 nmol/L); at 60 minutes, 228.2 nmol/L (range, 88.3-474.5
      nmol/L). CONCLUSION: Megestrol therapy was associated with the development of
      clinical adrenal insufficiency in our patients, as proved by rapid corticotropin
      test.

PMID- 9140274
TI  - What do physicians know about cryptosporidiosis? A survey of Connecticut
      physicians.
AB  - BACKGROUND: Cryptosporidiosis, an intestinal parasitic infection, has gained
      considerable media attention since a 1993 waterborne outbreak in Milwaukee, Wis,
      in which more than 400,000 persons became ill. However, the incidence of and risk
      factors for human cryptosporidiosis in the general US population are unknown. It
      has been suggested, but not documented, that physicians are generally unaware of
      the need to specifically request testing for this organism. OBJECTIVE: To assess
      physician awareness of cryptosporidiosis and knowledge of laboratory testing for
      Cryptosporidium oocysts. METHODS: A self-administered questionnaire was mailed to
      a stratified random sample of Connecticut physicians. Specialties were limited to
      physicians in internal medicine, gastroenterology, infectious disease,
      pediatrics, and family or general practice. Responses were compared among
      specialties. RESULTS: While most physicians were aware that cryptosporidiosis
      causes watery diarrhea (range, 67%-98%), particularly in patients with acquired
      immunodeficiency syndrome (> 85% of all specialties), many did not know the
      symptoms or failed to identify other groups at increased risk. More than 75% of
      gastroenterologists, general or family practitioners, internists, and
      pediatricians never or rarely order diagnostic testing for Cryptosporidium even
      when their patients have symptoms consistent with cryptosporidiosis. More than
      30% of physicians assumed Cryptosporidium testing was included in a standard ova
      and parasite examination. CONCLUSIONS: Cryptosporidiosis is likely to be
      unrecognized and underdiagnosed in Connecticut. This may occur because many
      physicians are unaware of cryptosporidiosis, unsure of the symptoms, do not test
      for it, or do not order the appropriate test. Unless there is more widespread use
      of specific tests, it will be difficult to evaluate specific preventive
      initiatives to limit the overall health impact of cryptosporidiosis.

PMID- 9140275
TI  - Patient-physician communication at hospital discharge and patients' understanding
      of the postdischarge treatment plan.
AB  - BACKGROUND: The quality of discharge planning is an important determinant of
      patient outcomes following hospital discharge. Patients often report inadequate
      discussion prior to discharge regarding major elements of the postdischarge
      treatment plan, including medication and daily activities. OBJECTIVE: To
      determine whether this apparent lack of communication might be the result of
      differing perceptions on the part of patients and physicians regarding the
      patients' understanding of the treatment plan. METHODS: We surveyed 99 patients
      and their attending physicians. All patients had been discharged recently from an
      academic medical center with the diagnosis of acute myocardial infarction or
      pneumonia. We asked both patients and physicians about time spent prior to
      discharge discussing the postdischarge treatment plan and the patients'
      understanding of this plan. McNemar test was used to determine whether responses
      of patients and physicians differed. RESULTS: Physicians reported spending more
      time discussing postdischarge care than did patients (P = .10). Physicians
      believed that 89% of patients understood the potential side effects of their
      medications, but only 57% of patients reported that they understood (P < .001).
      Similarly, physicians believed that 95% of patients understood when to resume
      normal activities, while only 58% of patients reported that they understood (P <
      .001). CONCLUSIONS: Physicians overestimate patients' understanding of the
      postdischarge treatment plan. Steps should be taken to improve communication
      about postdischarge treatment.

PMID- 9140276
TI  - Graves disease associated with autoimmune thrombocytopenic purpura.
AB  - Five patients with active Graves disease had moderate to severe autoimmune
      thrombocytopenic purpura at the time of diagnosis. Correction of hyperthyroidism
      and restitution of a euthyroid state by carbimazole therapy resulted in complete
      normalization of platelet counts.

PMID- 9140277
TI  - Do-not-resuscitate orders in the elderly: age discrimination or patient
      preference?

PMID- 9140278
TI  - Inhibiting acid production does not lead to reversion of Barrett's esophagus.

PMID- 9140279
TI  - History of fixed-dose combination therapy for hypertension.

PMID- 9140281
TI  - Enhancing autopsy performance and reporting.

PMID- 9140282
TI  - Pathologist's interaction with the physician office laboratory: an opportunity or
      an obligation?

PMID- 9140280
TI  - Primary adrenal leiomyosarcoma in acquired immunodeficiency syndrome.

PMID- 9140283
TI  - Utilization review for red cell transfusions. Are we just going through the
      motions?

PMID- 9140284
TI  - Interinstitutional comparison of frozen section consultations. A college of
      American Pathologists Q-Probes study of 90,538 cases in 461 institutions.
AB  - OBJECTIVE: To assess concordant, discordant, and deferred diagnosis rates from
      frozen sections; to determine reasons for discordance; to identify pathologic
      processes associated with discordant diagnoses; to determine false-positive or
      false-negative rates for neoplasms; and to identify anatomic sites associated
      with discordant frozen section diagnoses. DESIGN: Q-Probes study of the College
      of American Pathologists. PARTICIPANTS: Four hundred sixty-one institutions
      participating in the Q-Probes program from November 1, 1990, through March 31,
      1991. MAIN OUTCOME MEASURES: Concordant and discordant diagnosis rates. RESULTS:
      The frozen section concordance rate for diagnoses from the aggregate group was
      98.58% and the discordance rate was 1.42%, when uncorrected for deferred
      diagnoses. During the study period, participating institutions accessioned
      1,693,331 surgical pathology cases; 90,538 of these cases were evaluated by
      frozen section consultation, resulting in the examination of 121,668 specimens
      and 148,506 frozen section blocks. The majority of the frozen section
      discordances occurred because of misinterpretation of the original frozen section
      (31.8%), presence of diagnostic tissue in permanent sections of the frozen block
      when the frozen section was negative (30.0%), and presence of diagnostic tissue
      in the portion of the specimen not sampled by the frozen section (31.4%). Of the
      discordant diagnoses, 67.8% had false-negative diagnoses for neoplasm. The
      pathology processes and anatomic sites represented in discordant diagnoses are
      also evaluated. CONCLUSIONS: High diagnostic accuracy of frozen section
      consultations was demonstrated. Frozen sections are used to evaluate a variety of
      pathologic processes and anatomic sites.

PMID- 9140286
TI  - A rule-based expert system for laboratory diagnosis of hemoglobin disorders.
AB  - OBJECTIVE: To illustrate the utility of a rule-based expert system in diagnosing
      hemoglobin disorders. DESIGN: A rule-based expert system was developed for
      diagnosing hemoglobin disorders. This expert system runs on IBM-compatible
      personal computers and uses a backward-chaining search strategy to draw
      conclusions. Laboratory data (ie, results of hemoglobin electrophoresis,
      quantitative measurements of hemoglobin F and hemoglobin A2 levels, and result of
      a sickle cell screen) are processed by the system using defined rules to obtain a
      set of differential diagnoses. Additional data, such as hematologic parameters,
      ethnicity of the patient, and the presence or absence of certain clinical signs
      and symptoms, aid in making a final diagnosis. The rules in the current version
      of this expert system include diagnostic criteria for 71 hemoglobin disorders.
      SETTING: Regional academic medical center. PATIENTS: We tested the system by
      using 58 survey sample cases offered by the College of American Pathologists
      during the period of January 1989 through December 1994. MAIN OUTCOME MEASURE:
      The established diagnosis for a given case must be included in the list of
      differential diagnoses suggested by the expert system. RESULTS: The expert system
      included the actual diagnosis as one of the top four differential diagnoses in
      90% of the cases, whereas all the laboratories participating in the survey
      included it in 84% (mean) of the cases. CONCLUSION: We propose that this user
      friendly expert system is a potential tool for computer-assisted diagnosis of
      hemoglobin disorders.

PMID- 9140285
TI  - Are retrospective peer-review transfusion monitoring systems effective in
      reducing red blood cell utilization?
AB  - OBJECTIVE: This research used a study-control group design and examined data
      collected from five hospitals to evaluate the effectiveness of retrospective peer
      review systems on reducing utilization of red blood cells (RBCs). DESIGN: The
      effects of retrospective peer-review systems were studied in three parts: (1)
      trends of RBC utilization were compared by the slopes of linear regression lines
      that assessed the effect of time on RBC utilization among four study hospitals
      and one control hospital, (2) diagnosis-specific RBC utilization was compared
      between the control hospital and one matched study hospital, and (3) the effect
      of the retrospective review system of one study hospital was assessed by linear
      regression using data accumulated 1 year before and 2 years after implementation
      of the program. RESULTS: Three study hospitals showed no significant changes in
      RBC utilization during the 10-month study period. One study hospital and the
      control hospital demonstrated trends of reduced RBC use with negative slopes of
      regression lines; however, there was no difference in the degree of the two
      slopes, and the diagnosis-specific RBC utilization was not lower at the study
      hospital than at the control hospital. Furthermore, implementation of the
      retrospective peer-review system at one study hospital demonstrated no effect on
      RBC utilization. CONCLUSIONS: We conclude that the retrospective peer-review
      systems implemented at these four hospitals had no effect on reducing red blood
      cell utilization.

PMID- 9140287
TI  - Use of myeloperoxidase mRNA as a marker for myeloid lineage in acute leukemias.
AB  - BACKGROUND: Positivity for myeloperoxidase is considered the diagnostic hallmark
      of myeloid lineage and is the major criterion in the classification of acute
      leukemias. Early myeloid precursors, however, may be cytochemically negative for
      myeloperoxidase enzymatic activity or protein, but positive for myeloperoxidase
      mRNA. OBJECTIVE: To evaluate the expression of the myeloperoxidase gene in
      leukemic blasts at the mRNA level and correlate the expression with blast
      cytochemistry and immunophenotyping. PATIENTS AND METHODS: Sixteen cases of acute
      myelogenous leukemia and six cases of acute lymphoblastic leukemia were studied
      retrospectively using cellular material from Wright-stained and unstained
      archival smears of peripheral blood and bone marrow aspirate and a reverse
      transcription polymerase chain reaction procedure for detection of
      myeloperoxidase mRNA. RESULTS: Positivity in leukemic blasts was found in all
      acute myelogenous leukemia cases, including cases of M0, M1, and M5 that were
      cytochemically negative, equivocal, or weakly positive for the enzyme. None of
      the acute lymphoblastic leukemia cases showed positivity for myeloperoxidase
      mRNA. CONCLUSIONS: The procedure is a highly specific and sensitive method for
      diagnosis of myeloid lineage in leukemic blasts.

PMID- 9140288
TI  - Mantle cell lymphoma. Rapid polymerase chain reaction-based genotyping of a
      morphologically heterogeneous entity.
AB  - BACKGROUND: Mantle cell lymphoma is heterogeneous at the morphologic level. Since
      this B-cell lymphoma may be confused with other entities, ancillary molecular
      testing may be necessary for definitive diagnosis. A polymerase chain reaction
      based method, which is less complicated and more rapid than that generally
      available for the detection of immunoglobulin heavy chain (IgH) and bcl-1 gene
      rearrangements, would be helpful in this process. METHODS: Thirty-one mantle cell
      lymphoma samples (frozen or ethanol-preserved) from 29 patients were studied with
      two separate polymerase chain reaction assays using an air thermocycler and a low
      volume, capillary-tube format for rapid DNA amplification. The reverse primer,
      JH, was common to both assays. The forward primers were directed to the IgH
      framework III variable region (VH-FRIII) and the bcl-1 gene major translocation
      cluster. Agarose gels were used to evaluate amplicon. Additional product
      verification was also performed. RESULTS: Immunoglobulin heavy chain and major
      translocation cluster bcl-1 gene rearrangements were detected in all 29 (100%)
      and in 12 (41%) of 29 mantle cell lymphoma samples, respectively. Each VH
      FRIII/JH assay required 26 minutes to complete, whereas the major translocation
      cluster bcl-1/JH reaction required only 21 minutes. The seemingly low yield of
      bcl-1 gene rearrangements is not unexpected since this assay only detects major
      translocation cluster breakpoints. CONCLUSIONS: Presented is an extremely rapid,
      nonisotopic polymerase chain reaction-based method that detects IgH and major
      translocation cluster bcl-1 gene rearrangements in mantle cell lymphoma. Each
      polymerase chain reaction amplification was complete in 26 minutes or less,
      required only a 10-microL reaction volume, and exhibited adequate and specific
      product yield. This approach permits superior turnaround time and is thus
      advantageous in the clinical setting.

PMID- 9140289
TI  - Use of a physiologic oral glucose solution for screening for impaired glucose
      tolerance and non-insulin-dependent diabetes mellitus.
AB  - OBJECTIVE: To evaluate a lower osmolar, more physiologic oral glucose solution as
      part of an oral glucose tolerance test and to compare it to the standard glucose
      solution to see if it could serve as an effective screening agent for patients
      with impaired glucose tolerance or non-insulin-dependent diabetes mellitus.
      METHODS: A total of 100 subjects were given both the standard (1.38 mol/L) 75-g
      oral glucose tolerance test solution and the lower osmolar (0.62 mol/L) 50-g
      glucose solution. Each test was separated by at least 3 days. Blood samples were
      drawn at baseline and 30, 60, and 120 minutes after ingestion of each glucose
      solution. The 1- and 2-hour blood glucose values obtained using the 75-g oral
      glucose tolerance test beverage were used as the gold standard to diagnose
      diabetes according to World Health Organization criteria. RESULTS: Both solutions
      were shown to have a high sensitivity and specificity for detecting diabetes and
      impaired glucose tolerance at 30 and 60 minutes. CONCLUSIONS: The physiologic 50
      g solution uses less glucose, is highly palatable, and is similar in sweetness
      and carbohydrate concentration to commonly consumed soda beverages. A larger
      study including more patients with impaired glucose tolerance will need to be
      performed to verify our conclusions. The ability to perform high-sensitivity and
      high-specificity screening for patients with diabetes or impaired glucose
      tolerance with a single timed blood sample could make mass screening more
      practical.

PMID- 9140290
TI  - Fluorescence techniques for diagnosing intestinal microsporidiosis in stool,
      enteric fluid, and biopsy specimens from acquired immunodeficiency syndrome
      patients with chronic diarrhea.
AB  - OBJECTIVE: To evaluate three fluorescent chitin stains for detecting
      microsporidia spores in specimens from acquired immunodeficiency syndrome (AIDS)
      patients with chronic diarrhea. METHODS: We compared the Fungifluor, Calcofluor
      White, and Fungiqual A fluorochrome stains for identifying Enterocytozoon
      bieneusi and Septata intestinalis spores in stool, intestinal fluid, biopsy
      imprints, and paraffin biopsy sections. The modified chromotrope trichrome stain
      was used as the standard light microscopic technique for stool and fluid
      specimens. Stained and unstained paraffin sections and fluid preparations were
      also evaluated. Multiple specimens from 50 consecutive symptomatic AIDS patients
      and archival material from known microsporidia-positive AIDS patients were
      analyzed. RESULTS: Spores of E bieneusi and S intestinalis fluoresce brightly
      with all three fluorochrome stains in all of the types of diagnostic specimens.
      Fluorescing debris and the much larger fungal forms were readily distinguished.
      Spores were equally well detected in unfixed and formalin-fixed stool specimens,
      but were not as well detected after sodium acetate-acetic acid, polyvinyl
      acetate, and ethanol fixation. Bouin's tissue fixative gave a higher background
      staining than formalin. Spores were readily detected in archival paraffin
      sections and stool preparations, even when the specimens had been stained
      previously. Repeat fluorochrome staining was possible. The methods also could
      detect extraintestinal parasites in paraffin sections. CONCLUSION: The three
      fluorescent chitin stains are sensitive and rapid methods for detecting
      microsporidia spores in stool, intestinal fluid, biopsy imprint, and tissue
      specimens, even from archived material.

PMID- 9140291
TI  - Conjunctival oculosporidiosis in east Africa caused by Rhinosporidium seeberi.
AB  - BACKGROUND AND OBJECTIVE: Conjunctival rhinosporidiosis is an infectious disease
      rarely recorded outside the Indian subcontinent. The disease is caused by
      Rhinosporidium seeberi, an endosporulating microorganism of uncertain taxonomic
      classification. We report a series of cases manifesting this infection. MATERIAL
      AND METHODS: The demographic, clinical, and histopathologic data of 14 cases of
      conjunctival rhinosporidiosis on record at our Ophthalmic Pathology Laboratory
      were reviewed. RESULTS: All cases were from East Africa; 10 were from Malawi and
      4 from Kenya. Ten specimens were from males and three from females. Their age
      ranged from 7 to 20 years. All patients were treated by surgical excision, and no
      recurrence was recorded. None of the cases was diagnosed clinically as
      rhinosporidiosis. Histologically, all stages of the organism's life cycle could
      be found in the excised tissue, from small trophocytes to large sporangia
      containing sporoblasts. There were changes in histochemical stainings with growth
      and maturation. In general, the inflammation was of chronic nongranulomatous
      type. CONCLUSIONS: Conjunctival rhinosporidiosis is a rare infectious disease
      that typically appears in young males in rural regions, and that can be treated
      by surgical excision. It typically causes chronic nongranulomatous inflammation.
      Various stages of the R seeberi life cycle can be seen in the affected tissue.

PMID- 9140292
TI  - Conventional versus modified morphologic criteria for ganglioneuroblastoma. A
      review of cases from the Pediatric Oncology Group.
AB  - BACKGROUND: Conventional criteria for ganglioneuroblastoma (GNB) do not require
      the presence of ganglioneuromatous component for pathologic diagnosis. This leads
      to inclusion of a mixed variety of neuroblastic tumors in the category of GNB.
      Therefore, GNB diagnosed by conventional criteria includes tumors showing more
      than 5% ganglion cells but no predominant ganglioneuromatous component, as well
      as tumors containing predominant ganglioneuromatous component. By previously
      described modified criteria, the former would be considered differentiating
      neuroblastoma (NB), and only the latter would be considered GNB. Data on
      Pediatric Oncology Group cases were analyzed to compare the prognostic subgroups
      of GNB diagnosed by conventional and modified criteria. The two prognostic
      subgroups (low risk and high risk) were defined on the basis of previously
      described prognostic differences between histologic grades of differentiating NBs
      and subtypes of GNB. METHODS: Pathologic data from cases of neuroblastic tumors
      registered on Pediatric Oncology Group NB protocols 8104 and 8441 were reviewed.
      The GNBs diagnosed by conventional and modified criteria were divided into low
      risk and high-risk histology subgroups as follows: (1) GNB by conventional
      criteria: low-risk group, differentiating NB of histologic grades 1 and 2 and GNB
      of intermixed and borderline subtypes; high-risk group, differentiating NB of
      histologic grade 3 and GNB of nodular subtype; (2) GNB by modified criteria: low
      risk group, GNB of intermixed and borderline subtypes; high-risk group, GNB of
      nodular subtype. RESULTS: The low- and high-risk subgroups of GNBs diagnosed by
      conventional (69 cases) and modified (36 cases) criteria showed statistically
      significant differences in survival (P = .03 and .01, respectively). However,
      from the histologic point of view, GNBs diagnosed by modified criteria form a
      more uniform morphologic group, which can be divided into low- and high-risk
      subgroups by a single set of morphologic criteria. In contrast, GNBs diagnosed by
      conventional criteria form a heterogeneous group, which requires two sets of
      criteria (ie, histologic grade and subtypes of GNB) for its classification into
      low- and high-risk subgroups. CONCLUSIONS: The modified criteria for GNB define a
      morphologically uniform group of neuroblastic tumors to which a single set of
      prognostic criteria can be applied. It is recommended that the term GNB should be
      used both clinically and pathologically to designate a distinctive subgroup of
      neuroblastic tumors, in contrast to the current use, which designates both NB and
      GNB.

PMID- 9140293
TI  - Expansion of the cerebral ventricles and correlation with acquired
      immunodeficiency syndrome neuropathology in 232 patients.
AB  - BACKGROUND: Expansion of the cerebral ventricles is highly prevalent in patients
      with the acquired immunodeficiency syndrome (AIDS). The mechanism remains
      unclear. The purpose of this study was to correlate the volume of the cerebral
      ventricles with histopathologic abnormalities in the brain. METHODS: At autopsy,
      the volume of the cerebral ventricles in brain slices was estimated
      planimetrically in 232 patients with AIDS and 77 age-appropriate controls.
      Estimated volumes were compared with the neuropathologic results using multiple
      regression analysis. RESULTS: Multiple regression analysis demonstrated a
      significant relationship between ventricular volume and cerebral cytomegalovirus
      infection (P < .0004). When human immunodeficiency virus (HIV) encephalitis with
      multinucleated cells was present, median volume did not differ significantly from
      other subjects with AIDS. In 11 patients who had HIV-1 proviral DNA detected
      using the polymerase chain reaction, average volume was not different from 22
      patients who tested negatively using polymerase chain reaction. Ventricular
      expansion did not have a clear-cut neuropathologic substrate in many instances.
      CONCLUSIONS: In some subjects with AIDS, cytomegalovirus encephalitis was the
      underlying neuropathologic lesion associated with ventricular expansion. Key
      indicators of brain HIV-1 infection were related either weakly or not at all, and
      the role of HIV-1 remains uncertain in most cases.

PMID- 9140294
TI  - Veno-occlusive disease of the small bowel. An entity in search of identity.
AB  - Veno-occlusive disease of the bowel is a rare entity, and, to our knowledge, only
      two studies have been reported in the literature; these reports describe 11
      patients with veno-occlusive disease of the small and large bowels. We describe a
      patient who developed veno-occlusive disease of the small bowel, whose histologic
      findings were somewhat different from those previously reported.

PMID- 9140295
TI  - Morphologic characterization of polyvinyl sponge (Ivalon) breast prosthesis.
AB  - BACKGROUND: Although almost all breast implants are made of silicon, some
      implants, especially the ones used in early augmentation mammoplasty, were made
      of other materials, one of which is polyvinyl alcohol (commercially known as the
      Ivalon sponge). The morphology of this type of breast implant and its associated
      tissue reactions have not been characterized in detail. MATERIALS AND METHODS: A
      pair of polyvinyl breast prostheses implanted 40 years ago in a 66-year-old woman
      were removed together with their capsules to correct progressive disfiguration.
      The implants and capsules were radiographed. Sections from these specimens were
      subjected to routine histologic studies and special stains, including periodic
      acid-Schiff and Masson's trichrome stains. RESULTS: The breast implants were
      composed of crystals with a pathognomonic morphology. By hematoxylin-eosin stain,
      these crystals were polygonal, colorless, and refractile, but nonbirefringent,
      and they had a characteristic bubbling internal structure. The crystals displayed
      a deep-blue color with Masson's trichrome stain and were strongly periodic acid
      Schiff-positive, with or without diastase digestion. These crystals appeared
      isolated or interconnecting and were separated from one another by spaces filled
      with tissue fluid. The capsules were composed of the same kind of crystals, but
      they were heavily calcified and associated with dense fibrosis and occasional
      multinucleated giant cells. CONCLUSIONS: This case serves to emphasize that
      breast prostheses made of materials other than silicon may be rarely encountered
      in the surgical pathology laboratory. Although polyvinyl breast implants were
      abandoned, injection of polyvinyl into various tissues for therapeutic purposes
      is sometimes indicated. The morphologic features of polyvinyl as detailed in this
      study should enable prompt and accurate recognition of this material, whether it
      is in breast implants or other types of tissue.

PMID- 9140297
TI  - Papillary parathyroid adenoma. A rare occurrence and its importance in
      differentiation from papillary carcinoma of the thyroid.
AB  - The case of a 67-year-old woman with primary hyperparathyroidism manifested by
      hypercalcemia with anorexia, nausea, and weakness; low serum phosphorus; high
      circulating parathyroid hormone; and mildly elevated calcitriol and parathyroid
      hormone-related protein is reported. A cystic lesion was removed from the
      inferior pole of the right lobe of the thyroid, and serum calcium levels rapidly
      returned to normal. The lesion was proven histologically to be a parathyroid
      adenoma with predominate papillary features. The differentiation of such a rare
      lesion from papillary carcinoma of the thyroid, both histologically and
      cytologically, is stressed.

PMID- 9140296
TI  - Papillary transitional cell carcinoma arising in a calyceal cyst and masquerading
      as a renal cyst.
AB  - We report the case of a 74-year-old man with a papillary transitional cell
      carcinoma, grade 1-2/3, growing within a bilobated calyceal cyst, measuring up to
      8.5 cm in diameter, and masquerading as a simple renal cyst. The cyst was lined
      by atrophic simple and transitional epithelium and showed intracystic hemorrhage.
      Leakage of blood into the calyx was probably the cause of the hematuria for which
      the patient presented. However, with retrograde pyelography and careful gross
      examination of the excised kidney, no communication of the pyelocalyceal system
      with the cyst could be identified. By ultrasound examination and computerized
      tomographic scan the lesion showed several small renal cysts, measuring up to 1.1
      cm in diameter, as well as several hepatic parenchymal cysts. To our knowledge,
      this is the first report of a papillary transitional cell carcinoma arising from
      a cyst of calyceal origin.

PMID- 9140298
TI  - The immune system following bone marrow transplantation.

PMID- 9140299
TI  - The autopsy conference.

PMID- 9140300
TI  - Epithelioid cells in myoid hamartoma of the breast.

PMID- 9140301
TI  - Intrathoracic extramedullary hematopoietic tumor in hemoglobin C disease.

PMID- 9140302
TI  - Intrathoracic extramedullary hematopoietic tumor in hemoglobin C disease.

PMID- 9140303
TI  - Accuracy in mammographically directed breast biopsies: communication is key.

PMID- 9140304
TI  - Pilot studies for proficiency testing using fluorescence in situ hybridization
      with chromosome-specific DNA probes: a College of American Pathologists/American
      College of Medical Genetics Program.
AB  - Fluorescence in situ hybridization using chromosome-specific DNA probes is
      rapidly becoming part of clinical laboratory practice for certain congenital and
      neoplastic disorders. Current legislation requires proficiency testing for
      clinical laboratory studies. To evaluate the efficacy of fluorescence in situ
      hybridization proficiency testing, we invited 19 representative institutions to
      participate in three pilot studies. One study used probes for the X and Y
      chromosomes to evaluate metaphase spreads and interphase nuclei. Another study
      used probes for bcr and abl to detect bcr/abl fusion in interphase nuclei in
      chronic myelogenous leukemia. The third study used a D22S75 probe to detect
      microdeletions in metaphase spreads from a patient with velocardiofacial
      syndrome. The results of these studies demonstrate that proficiency testing with
      fluorescence in situ hybridization is attainable using either metaphase or
      interphase preparations, and that either microscope slides or fixed cell pellets
      are suitable.

PMID- 9140305
TI  - Practice guidelines for autopsy pathology: the perinatal and pediatric autopsy.
      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 reporting of perinatal and pediatric autopsies. The guideline
      is to be regarded as being primarily an educational tool. Application of these
      recommendations on autopsy reporting is to be made on the basis of the judgment
      of the pathologist engaged in a specific case.

PMID- 9140306
TI  - Principles for including or excluding 'mechanisms' of death when writing cause-of
      death statements.
AB  - OBJECTIVE: To develop principles and refined definitions designed to improve the
      content of cause-of-death statements regarding inclusion or exclusion of so
      called mechanisms of death. DATA SOURCES: Survey of readily available instruction
      manuals and other literature regarding mechanisms of death and instructions for
      death certificate completion. DATA SYNTHESIS: Definitions and principles
      contained in the information sources were reviewed, and a set of specific
      principles, criteria, and definitions were written. These principles are
      consistent with, but are more extensive and practically applicable than, those
      found in each of the information sources surveyed and may be used to decide which
      conditions to report in cause-of-death statements. CONCLUSIONS: Mechanisms of
      death include a defined list of terminal events (such as asystole) and a larger
      group of nonspecific physiologic derangements (such as portal hypertension) and
      are differentiated by definition from nonspecific anatomic processes (such as
      cirrhosis). Three principles may be applied in individual cases. Principle 1
      states that terminal events are not reported in cause-of-death statements.
      Principle 2 states that a nonspecific physiologic derangement or a nonspecific
      anatomic process should be reported if (1) it is a recognized, potentially fatal
      complication of the underlying cause of death; (2) it constitutes part of the
      sequence of conditions that led to the death of the patient in question; (3) it
      is not a symptom or sign; (4) its existence in the patient would not be apparent
      unless included and explicitly stated in the cause-of-death statement; (5) its
      inclusion does not constitute an oversimplification of the facts; and (6) an
      etiologically specific underlying cause of death is also reported. Principle 3
      states that if the existence of the complication is obvious based on the
      underlying cause of death or another reported complication, it need not be
      reported.

PMID- 9140307
TI  - CD4 and CD8 antigen coexpression: a flow cytometric study of peripheral blood,
      bone marrow, body fluid, and solid lymphoreticular specimens.
AB  - OBJECTIVE: CD4 and CD8 antigen coexpression occurs not only on blastic T-cell
      malignancies, but also on a small subset of mature lymphocytes. The aim of this
      study was to determine the prevalence of this population of cells and to identify
      features that can be used to differentiate them from T lymphoblasts. DESIGN: All
      specimens submitted to the clinical flow cytometry laboratory from August 1,
      1994, through July 31, 1995, were analyzed for CD4 and CD8 coexpression. MAIN
      OUTCOME MEASURE: Percentage of lymphocytes coexpressing the CD4 and CD8 antigens.
      RESULTS: Four percent (22/526) of all specimens contained a population of CD4/CD8
      coexpressing cells. Five cases represented CD4 and CD8 antigen expression on
      neoplastic cells. In 17 cases, the CD4/CD8 coexpressing cells appeared to
      represent a population of mature lymphocytes with a normal phenotype. The
      immature cells of T-cell acute lymphocytic leukemia and lymphoblastic lymphoma
      represented a dominant uniform population of cells demonstrating strong staining
      with both the CD4 and CD8 antigens. Cases containing a mature population of
      CD4/CD8 coexpressing cells were characterized by fewer coexpressing cells and
      variable expression of CD8. There were cases where distinction of this population
      of mature CD4/CD8 coexpressing lymphoid cells from a blastic malignancy was not
      possible using immunophenotyping alone. CONCLUSION: Correlation of clinical,
      morphologic, and immunophenotypic data is recommended to prevent the misdiagnosis
      of subtle involvement by a blastic T-cell malignancy.

PMID- 9140308
TI  - Variation of free and total prostate-specific antigen levels: the effect on the
      percent free/total prostate-specific antigen.
AB  - OBJECTIVE: Recent studies have shown that calculations of the percent free/total
      prostate-specific antigen (PSA) improves the specificity of PSA testing.
      Characterizing the variability of free PSA and total PSA is necessary to evaluate
      the utility of an isolated free/total PSA measurement. We investigated the total
      variation of free and total PSA levels to determine how the percent free/total
      PSA was affected. DESIGN: Serum was obtained from nine urological patients on 5
      different days over a 2-week period. Free and total PSA levels were measured on
      the day of collection. The total variation expressed in terms of percent
      coefficient of variation (%CV) was calculated, and the biological variation was
      derived taking analytical variation into consideration. SETTING: Patients were
      from Seattle (Wash) Urological Associates, and samples were processed at the
      Dynacare Laboratory of Pathology, Seattle, Wash. PATIENTS: Nine men (aged 48 to
      69 years) were evaluated; three had been diagnosed with prostate cancer, three
      with benign prostatic hyperplasia, one with chronic prostatitis, one with high
      grade prostatic intraepithelial neoplasia, and one was clinically normal. MAIN
      OUTCOME MEASURES: Total variation for free, total, and percent free/total PSA.
      RESULTS: The average total variation was 13.9% CV, 7.5% CV, and 10.6% CV for
      free, total, and percent free/ total PSA, respectively. Biological variation was
      derived to be 13.0% CV, 5.6% CV, and 8.0% CV for free, total, and percent
      free/total PSA, respectively. CONCLUSIONS: When applied, these results suggest
      that there are significant random changes in the numerator and denominator of the
      free PSA-total PSA ratio that could result in clinical misinterpretation.
      Clinicians must be aware that free PSA and total PSA levels will fluctuate owing
      to nonpathologic variation.

PMID- 9140309
TI  - Lack of cross-reactivity of Ambien (zolpidem) with drugs in standard urine drug
      screens.
AB  - OBJECTIVE: To determine in healthy volunteers (men and women; 18 to 40 years old)
      the potential cross-reactivity of Ambien (zolpidem) and/or its metabolites with
      drugs that are screened by the Syva EMIT II and the Abbott ADx urine drug screens
      assays. DESIGN: Open-label, fixed-treatment sequence of 1 night each of treatment
      with zolpidem (10 mg) and temazepam (15 mg). SETTING: Clinical Pharmacology Unit
      within a teaching hospital. MAIN OUTCOME MEASURES: Over a 24-hour period,
      presence or absence of positive results on the Syva EMIT II or the Abbott ADx
      urine drug assay system, each performed at two different laboratory assay sites.
      RESULTS: Following ingestion of zolpidem, no subject had any positive response in
      either laboratory to the Syva EMIT II or the Abbott ADx urine drug screen assays
      at 0, 4, 8, 12, and 24 hours postdose. During the same time period, all subjects
      had measurable zolpidem plasma concentrations at 1.5 and 8 hours postdose, with
      mean concentrations of 115.2 ng/mL and 30.1 ng/mL, respectively (in agreement
      with its half-life of 2.5 hours). The positive response rate at 10 hours after
      ingestion of Restoril (temazepam) among the four laboratory/assay combinations
      ranged from 36.8% to 73.7%, a range that is within the reported response rates
      for these tests. CONCLUSIONS: These data indicate that zolpidem will not cross
      react in standard urine drug screens with benzodiazepines, opiates, barbiturates,
      cocaine, cannabinoids, or amphetamines.

PMID- 9140310
TI  - p53 gene mutations and p53 protein expression in human soft tissue sarcomas.
AB  - OBJECTIVE: To determine the frequency of mutation and overexpression of the p53
      tumor suppressor gene in human soft tissue sarcomas. DESIGN: A total of 31 soft
      tissue sarcomas were analyzed by immunohistochemistry for the expression of p53
      protein and were subsequently investigated by the polymerase chain reaction
      technique and direct sequence analysis of exons 5 through 8 in the p53 gene.
      SETTING: The specimens were collected over a 3-year period in the laboratories at
      our large teaching hospital in Seoul, Republic of Korea. PATIENTS: Thirty-one
      patients with soft tissue tumor were surgically treated and diagnosed as having
      either malignant fibrous histiocytoma, rhabdomyosarcoma, or leiomyosarcoma.
      RESULTS: Overexpression of p53 was seen in 17 (55%) of 31 sarcomas, including 9
      (64%) of 14 malignant fibrous histiocytomas, 4 (44%) of 9 rhabdomyosarcomas, and
      4 (50%) of 8 leiomyosarcomas. Seven cases (23%) demonstrated mutations in the p53
      gene. Six had a single mutation, whereas one showed triple mutations. There were
      seven mutations in exon 5, one in exon 6, and one in exon 7. All of the mutations
      were missense mutations, resulting in changes in the predicted amino acid
      sequence. Among the nine mutations, seven (78%) were transversions and two (22%)
      were transitions. CONCLUSIONS: Mutation of the p53 tumor suppressor gene, with
      resultant overexpression of p53 protein, frequently occurs in human soft tissue
      sarcomas, supporting the role of p53 mutations in the pathogenesis of soft tissue
      sarcoma and the possible usefulness of p53 immunolocalization as a screening
      method for p53 mutations.

PMID- 9140311
TI  - Detection of hepatitis C virus RNA sequences in hepatocellular carcinoma and its
      precursors by microdissection polymerase chain reaction.
AB  - OBJECTIVE: Chronic hepatitis C virus (HCV) infection is frequently associated
      with the development of hepatocellular carcinoma (HCC), but the mechanism of
      malignant transformation is unknown. To analyze the association of HCV with HCC,
      we developed a microdissection technique for the detection by polymerase chain
      reaction of positive (genomic)- and negative (replicative)-strand HCV RNA in
      histologically confirmed HCC and the surrounding cirrhotic and macroregenerative
      nodules. MATERIALS AND METHOD: Five HCCs and one macroregenerative nodule and the
      surrounding cirrhotic liver tissues of all cases were selected for this study.
      The method entails extraction of RNA from selected areas of formalin-fixed,
      hematoxylin-stained histologic sections, followed by strand-specific reverse
      transcription double polymerase chain reaction and Southern blotting. RESULTS:
      Positive- and negative-strand HCV RNA sequences were detected in five of six
      tumors and the surrounding cirrhotic livers. CONCLUSIONS: These results verify
      the method of polymerase chain reaction detection of HCV RNA from histologically
      defined, selected lesions. In addition, the findings suggest that HCV RNA
      persists and replicates in hepatocytes during malignant transformation.

PMID- 9140312
TI  - Immunocytochemical localization of macrophage migration inhibitory factor in
      human hypophysis and pituitary adenomas.
AB  - OBJECTIVE: To establish the presence of macrophage migration inhibitory factor
      (MIF) in human nontumorous and adenomatous pituitaries. DESIGN, SETTING, AND
      PATIENTS: Macrophage migration inhibitory factor was demonstrated by
      immunocytochemistry on paraffin sections with a polyclonal antirecombinant murine
      MIF using the streptavidin-biotin-peroxidase complex method. Nontumorous
      hypophyses (14 cases) obtained from autopsy and 54 surgically removed pituitary
      adenomas were studied. In nontumorous pituitaries, serial sections were
      immunostained for both pituitary hormones and MIF. RESULTS: Macrophage migration
      inhibitory factor was localized in all corticotrophs, including basophils
      extending into the posterior lobe, Crooke's cells, and a few thyrotrophs. The
      posterior lobe was immunonegative for MIF. Densely (five cases) and sparsely (six
      cases) granulated somatotroph and lactotroph (six cases) adenomas lacked MIF
      immunostaining. Macrophage migration inhibitory factor was found in 3 of 4
      thyrotroph adenomas, 3 of 6 gonadotroph adenomas, 10 of 11 functioning
      corticotroph and 8 of 10 silent corticotroph adenomas, 3 of 3 null cell adenomas,
      and 3 of 3 oncocytic adenomas. The immunopositivity was diffuse or focal, and the
      intensity was variable. CONCLUSIONS: This study is the first to demonstrate the
      presence of MIF in human nontumorous and adenomatous pituitaries using an
      immunocytochemical staining technique.

PMID- 9140313
TI  - Pleomorphic medium-sized T-cell lymphoma following Hodgkin's disease (nodular
      sclerosis type).
AB  - We describe a 32-year-old woman who presented with Hodgkin's disease, nodular
      sclerosis type II, subtype I, which necessitated several treatments over 11
      years. The patient then developed pleomorphic, medium-sized T-cell lymphoma,
      which had a fatal outcome within 13 months. The role of radiotherapy,
      splenectomy, and chemotherapy in second tumor induction is compared with other
      sequential T-cell lymphomas. The significance of rare Epstein-Barr virus-infected
      cells during the T-cell lymphoma extension is discussed.

PMID- 9140314
TI  - Coinfection with Giardia lamblia and Enterocytozoon bieneusi in a patient with
      acquired immunodeficiency syndrome and chronic diarrhea.
AB  - Diarrhea is an important clinical problem in immunosuppressed patients with
      acquired immunodeficiency syndrome (AIDS). There are numerous classical as well
      as emerging enteric pathogens that can produce diarrhea; however, these agents
      can be missed when only one method, such as microbiological examination of stool,
      is used for diagnosis. The endoscopic biopsy is a sensitive method for diagnosis
      of many viral, fungal, and parasitic infections of the gastrointestinal tract.
      Although only one agent is often identified in mucosal biopsies from these
      immunosuppressed patients, coinfection with multiple microbial agents is being
      increasingly recognized. Giardia infection is not as prevalent as other pathogens
      in patients with AIDS, but it remains an important diarrheal agent that is
      potentially curable. However, there have been only rare reports of coinfections
      with giardiasis and other infectious agents. This report describes a patient with
      AIDS and chronic diarrhea who had repeated negative stool examinations for ova
      and parasites. Light and electron microscopic examination of subsequent
      endoscopically obtained small intestinal biopsies revealed coinfection with two
      parasites, Enterocytozoon bieneusi and Giardia lamblia. Following treatment with
      metronidazole for giardiasis, the diarrhea persisted, but was less severe. This
      report also describes the diagnostic features of Giardia and Enterocytozoon
      infections in biopsy tissues and emphasizes the importance of identifying enteric
      coinfections in patients with AIDS to ensure timely and specific modes of
      therapy.

PMID- 9140315
TI  - Bone marrow mastocytosis associated with an undifferentiated extramedullary tumor
      of hemopoietic origin.
AB  - The case of a 62-year-old man who presented with acute abdominal pain and a
      widespread tumor involving the retroperitoneum is described. Three weeks after
      initial presentation, the patient died suddenly of acute cardiac failure with
      signs of arrhythmia. Autopsy revealed a disseminated tumor with infiltration of
      the retroperitoneal fat, as well as nodules in the left testis and the right
      atrium. The tumor cells were reactive for CD45, vimentin, and chloroacetate
      esterase, but were unreactive with a broad spectrum of antibodies against
      myelomonocytic and lymphocytic antigens and with antibodies against tryptase and
      c-kit (CD117), which are characteristic markers for mast cells. However, the bone
      marrow exhibited the typical picture of mastocytosis, with disseminated clusters
      of differentiated spindle-shaped cells that stained strongly for tryptase, c-kit,
      and chloroacetate esterase. No infiltrates of well-differentiated mastocytosis
      could be detected in any of the extramedullary tissues investigated. A diagnosis
      of bone marrow mastocytosis with an associated undifferentiated extramedullary
      tumor of hemopoietic origin was established. By definition, the extramedullary
      tumor could not be diagnosed as a granulocytic sarcoma or (differentiated)
      mastocytoma, but the possibility that a mast cell progenitor could be involved in
      the evolution of both tumors cannot be ruled out.

PMID- 9140316
TI  - Citalopram overdose--review of cases treated in Swedish hospitals.
AB  - BACKGROUND: The toxic effects of acute citalopram overdose are reported by the
      Swedish Poisons Information Centre. DESIGN: Case reports received from Swedish
      hospitals during 1995 have been analyzed. Forty-four cases of pure citalopram
      intoxication have been studied in detail. RESULTS: At doses below 600 mg, mild
      symptoms were observed. Doses above 600 mg caused ECG abnormalities and
      convulsions in some patients, while doses greater than 1900 mg caused such
      symptoms in all patients. CONCLUSIONS: The findings are consistent with previous
      reports claiming that selective serotonin reuptake inhibitors are less toxic
      compared to tricyclic antidepressants. However, there is a risk of developing
      serious symptoms when large doses have been ingested.

PMID- 9140317
TI  - Lung injury related to consuming Sauropus androgynus vegetable.
AB  - BACKGROUND: Taking Sauropus androgynus, a Malaysian food, to reduce weight began
      as a fad in Taiwan in 1994. Some advocates of this fad developed pulmonary
      dysfunction. The aim of this study is to report the lung injury in patients
      taking Sauropus androgynus. METHODS: From July 1995 to November 1995, we
      investigated 104 nonsmoking patients (one male and 103 females) with chest
      roentgenography, pulmonary function, test, and Technetium 99m-labeled diethylene
      triamine penta-acetate (Tc-99m DTPA) radioaerosol inhalation lung scintigraphy.
      RESULTS: Among the 90 patients receiving Tc-99m DTPA inhalation lung scan, 46
      (51.1%) patients had increased clearance of Tc-99m DTPA from lung and 20 (22.2%)
      patients had inhomogeneous deposition of the submicronic radioaerosol. Eighteen
      (18/100) patients had obstructive ventilatory impairment in pulmonary function
      test. Analyzing the results, we found that the patients with respiratory symptoms
      (n = 42) took more vegetables (p = 0.016), had increased clearance of Tc-99m DTPA
      (p = 0.010) and had lower FEV1 (p = 0.001), FEV1/FVC (p < 0.001), FEF25-75 (p =
      0.001), VC (p = 0.002) and DLCO (p = 0.009) than the patients without respiratory
      symptoms (n = 62). FEV1 and FEV1/FVC were significantly reduced in patients with
      severe impairment of alveolar permeability. The cumulative dosage and duration of
      exposure were significantly associated with the reduction of FEV1 and FEV1/FVC.
      CONCLUSION: The lung injury after taking Sauropus androgynus involves alveoli
      and/or small airways and is manifest as obstructive ventilatory impairment with
      inhomogeneous aerosol distribution and increased lung epithelial permeability.

PMID- 9140318
TI  - A foodborne disease outbreak due to the consumption of moldy sorghum and maize
      containing fumonisin mycotoxins.
AB  - BACKGROUND: Unseasonal rains beginning in 1995 damaged the maize and sorghum
      crops harvested in a few villages of the Deccan plateau in India. Human
      consumption of those grains resulted in a foodborne disease outbreak
      characterized by abdominal pain, borborygmi and diarrhea. METHODS: A rapid
      epidemiological survey was conducted in the affected villages and a detailed
      house to house survey in selected villages. RESULTS: People in 27 out of 50
      villages surveyed were affected and disease was seen only in households and
      subjects consuming the rain damaged moldy sorghum or maize. The disease was self
      limiting. Diarrhea was reproduced in day old cockerels fed contaminated grains
      from affected households. All 20 sorghum and 12 maize samples collected from
      affected households had Fusarium sp. as the dominant mycoflora and contained
      fumonisin B1 in the range of 0.14-7.8 mg/kg and 0.25-64.7 mg/kg, respectively. In
      contrast, samples collected from unaffected households had fumonisin B1 in low
      levels ranging from 0.07-0.36 mg/kg and 0.05-0.24 mg/kg, respectively.
      CONCLUSION: The higher water activity in the grains left in the field following
      harvest led to the production of high levels of fumonisin B1 and consumption of
      such grains by humans resulted in the disease.

PMID- 9140319
TI  - Delayed administration of Vipera xanthina palaestinae antivenin.
AB  - INTRODUCTION: Vipera xanthina palaestinae is the most widely distributed venomous
      snake in Israel, accounting for most envenomations. A specific equine antivenin
      is efficacious against both systemic and local manifestations if given within
      hours. This study sought to determine if delayed vipera xanthina palaestinae
      antivenin can be effective. METHODS: Patients who had been bitten by vipera
      xanthina palaestinae during 1991-1995 were evaluated. Those who continued to
      deteriorate beyond 24 h post envenomation, in spite of treatment or because of
      delayed diagnosis, were given vipera xanthina palaestinae antivenin. RESULTS: Ten
      patients were included in the study. Vipera xanthina palaestinae was identified
      in seven and diagnosis was considered probable in three patients. On admission,
      eight patients had local signs and seven patients had mild to severe systemic
      manifestations. The local signs were remarkable and progressive in all patients.
      In five, systemic signs and laboratory abnormalities were delayed as well. The
      time range for delayed antivenin administration was 1-6 days after envenomation.
      Following antivenin administration, progression of local signs ceased in all
      patients and swelling regressed within 24 h. In nine patients this occurred
      within 6 h. CONCLUSION: Vipera xanthina palaestinae antivenin administration
      should be considered in patients with envenomations complicated by marked and
      progressive local signs, delayed systemic signs and laboratory abnormalities more
      than 24 h after envenomation.

PMID- 9140320
TI  - Effect of delayed administration of activated charcoal on the absorption of
      conventional and slow-release verapamil.
AB  - OBJECTIVE: To investigate the effect of simultaneous and delayed administration
      of activated charcoal on the absorption of two verapamil formulations. METHODS:
      In the first study, 9 healthy volunteers received the following treatments: 1)
      verapamil 80 mg (conventional formulation) with 50 mL water only, 2) verapamil 80
      mg and 25 g activated charcoal immediately afterwards, and 3) verapamil 80 mg
      with 50 mL water, followed by 25 g charcoal 2 h after verapamil ingestion. In the
      second study, 8 healthy volunteers received the following treatments: 1)
      verapamil 240 mg (slow-release formulation) with 50 mL water only, 2) verapamil
      slow-release 240 mg and 25 g activated charcoal immediately afterwards, 3)
      verapamil slow-release 240 mg with 50 mL water, followed by 25 g charcoal 2 h
      after verapamil ingestion, and 4) verapamil slow-release 240 mg with 50 mL water,
      followed by 25 g charcoal 4 h later. Plasma verapamil concentrations over 24 h
      were measured by high performance liquid chromatography. RESULTS: Activated
      charcoal given immediately after the conventional formulation of verapamil
      reduced the AUC0-24 h by 99% (p < 0.0005) and the Cmax by 98% (p < 0.0005). When
      the administration of charcoal was delayed 2 h, no significant change in
      verapamil absorption was observed. With the slow-release formulation of
      verapamil, charcoal given immediately after verapamil ingestion reduced the
      verapamil AUC0-24 h by 86% (p = 0.001) and the Cmax by 82% (p = 0.002). When the
      administration of charcoal was delayed 2 or 4 h, the AUC0-24 h was reduced by 35%
      (p = 0.04) and 32% (p = 0.001), respectively, but the Cmax was decreased by 13%
      (p = NS) and 9% (p = NS) only. CONCLUSIONS: Activated charcoal was effective in
      preventing absorption of verapamil when it was administered immediately after
      verapamil ingestion. In the case of slow-release formulation, charcoal reduced
      verapamil absorption by over 30% even when given 4 h after verapamil.

PMID- 9140321
TI  - In vitro adsorption study of fluoxetine onto activated charcoal at gastric and
      intestinal pH using high performance liquid chromatography with fluorescence
      detector.
AB  - BACKGROUND: This in vitro investigation was performed to study the adsorption
      characteristics of fluoxetine to activated charcoal and its commercial
      formulation Carbomix powder in simulated gastric (pH = 1.2) and intestinal (pH =
      7.2) fluid environments. METHODS: Solutions containing fluoxetine and charcoal
      were incubated at 37 degrees C for one hour. Reversed phase high performance
      liquid chromatography was used for the determination of free fluoxetine
      concentrations (range 0.2-8 micrograms/mL) in the diluted filtrate. RESULTS: The
      maximum adsorption capacities at pH 1.2 for activated charcoal and Carbomix were
      223 and 333 mg/g, respectively; at pH 7.2 they were 301 and 453 mg/g,
      respectively. The affinity constant values at pH 1.2 of activated charcoal and
      Carbomix were 441 and 122 L/g, respectively, while at pH 7.2 they were 482 and
      589 L/g, respectively, indicating a strong binding of fluoxetine onto charcoals.
      CONCLUSIONS: Relative to the toxic and lethal doses in cases of fluoxetine
      intoxications, both types of charcoals tested were found effective for adsorption
      at gastric and intestinal pH. Adsorbed fluoxetine was significantly increased at
      intestinal pH, consistent with predominant adsorption of the undissociated form
      of the drug. We conclude that activated charcoal and Carbomix have adsorptive
      properties appropriate to medical treatment in cases of fluoxetine overdose.

PMID- 9140323
TI  - Quality management for poison centers.
AB  - BACKGROUND: Poison centers are struggling with the concept of service quality and
      how to improve it. The business world has dealt with this concept by establishing
      internationally agreed-upon criteria for quality management. Poison centers
      deliver health care services and can benefit from the approach taken by the
      corporate community. METHODS: This review article takes the criteria of quality
      management proposed by the ISO 9000 series guidelines and demonstrates their
      applicability to poison center operations by translating the business jargon of
      the ISO 9000 series into terminology more familiar to health care professionals
      and by providing examples and approaches to satisfy specific guidelines. This
      article offers poison center staff a framework to help them understand how to
      improve the quality of service they provide.

PMID- 9140322
TI  - Aluminum in enteral nutrition formulas and parenteral solutions.
AB  - BACKGROUND: To examine the aluminum content of several commercially available
      enteral nutrition formulas and parenteral solutions. METHODS: Twelve enteral
      nutrition formulas and 10 parenteral solutions were commonly used in routine
      clinical care of patients and obtained from different medical companies in
      Turkey. The aluminum contents were determined by electrothermal atomic absorption
      spectrophotometry. RESULTS: We found that aluminum concentration in the enteral
      nutrition formulas and the parenteral solutions to range from 87.6 to 961.2 ng/mL
      and 58.4 to 1232.0 ng/mL, respectively. CONCLUSIONS: Careful clinical and
      biochemical monitoring are warranted to determine whether it will be necessary to
      eliminate aluminum contamination of enteral and parenteral preparations used in
      patients, particularly infants, with reduced kidney function who may be at risk
      for aluminum intoxication.

PMID- 9140324
TI  - Bradycardia in toluene poisoning.
AB  - BACKGROUND: Tachyarrhythmias are the classical manifestation of toluene
      cardiotoxicity. The presumed mechanism is sensitization of the myocardium to the
      potential arrhythmogenic effect of endogenous catecholamines, occasionally
      resulting in fatality. Bradyarrhythmias have been repeatedly shown in animal
      models, but have been reported only once in a human. CASE REPORTS: Two patients
      with toluene intoxication presented with severe sinus bradycardia. One patient
      had also atrial-ventricular dissociation. In both cases cardiac rhythm returned
      to normal within several hours. CONCLUSION: We suggest that the spectrum of
      cardiotoxic symptoms associated with toluene intoxication in humans includes
      bradyarrhythmias as well as tachyarryhthmias.

PMID- 9140326
TI  - Sulfide poisoning.

PMID- 9140325
TI  - Calcium polysulfide overdose: a report of two cases.
AB  - BACKGROUND: Calcium polysulfide or lime-sulfur solution is a common agricultural
      product used as a fungicide. Despite its easy availability, only two prior cases
      of intentional ingestion, both from Japan, have been reported in the literature.
      CASE REPORTS: Two cases of calcium polysulfide ingestion are presented. In the
      first case severe acidosis, coma and cardiac arrest occurred. Despite aggressive
      supportive therapy, the patient expired. Autopsy examination revealed hemorrhagic
      necrosis of the gastric mucosa. The second patient also exhibited altered mental
      status and metabolic acidosis. He experienced liver dysfunction, rhabdomyolysis,
      renal dysfunction, and aspiration pneumonia. He had endoscopically proven
      esophageal and gastric mucosal burns which developed into esophageal strictures.
      CONCLUSIONS: Calcium polysulfide ingestions cause direct caustic injury to the
      upper gastrointestinal tract, coma and severe metabolic acidosis.

PMID- 9140327
TI  - Survival after a massive hydrofluoric acid ingestion.
AB  - BACKGROUND: Hydrofluoric acid ingestion is known to have a very high mortality
      rate secondary to the rapid development of hypocalcemia and fatal arrhythmias.
      CASE REPORT: A 33-year-old man ingested an estimated dose of hydrofluoric acid 6
      times that considered to be lethal. The patient survived with minimal morbidity
      despite having multiple ventricular fibrillation arrests. His survival is
      attributed to early, high dose calcium therapy given via the nasogastric and
      intravenous routes.

PMID- 9140328
TI  - Recurrent ventricular tachyarrhythmias associated with QT prolongation following
      hydrofluoric acid burns.
AB  - BACKGROUND: Some hydrofluoric acid burns appear initially as only a slight wound,
      but patients may show dramatic changes within several hours. The extent of such
      burns are directly related to the concentration, amount, and duration of
      exposure. CASE REPORT: A 64-year-old man sustained 44% total body surface burns
      after exposure to 30% hydrofluoric acid. Approximately 5 h after injury, he
      developed recurrent ventricular tachycardia and ventricular fibrillation which
      occurred in conjunction with long QT syndrome. In this case, the occurrence of
      hypocalcemia and especially hypomagnesemia played an important role in the
      development of long QT syndrome.

PMID- 9140329
TI  - Bromism from excessive cola consumption.
AB  - BACKGROUND: Bromism is an unusual occurrence. Historically bromism has been known
      to occur with chronic ingestion of bromide salts used as sleep medications. In
      this case, excessive consumption of a cola with brominated vegetable oil caused a
      severe case of bromism. CASE REPORT: The patient presented with headache,
      fatigue, ataxia, and memory loss which progressed over 30 days. He consumed 2 to
      4 L of cola containing brominated vegetable oil on a daily basis before
      presenting with these symptoms. His significantly elevated serum chloride, as
      measured by ion specific methods, and negative anion gaps were overlooked during
      a prior hospitalization and emergency department visits. A focal neurologic
      finding of right eyelid ptosis led to an extensive evaluation for a central
      nervous system lesion. The patient continued to deteriorate, until he was no
      longer able to walk. A diagnosis of severe bromism was eventually made and his
      serum bromide was confirmed at 3180 mg/L (39.8 mmol/L). Despite saline loading
      the patient failed to improve but subsequent hemodialysis dramatically cleared
      his clinical condition, and reduced his serum bromide levels. The unilateral
      eyelid ptosis, a rarely reported finding in bromism, also resolved with
      hemodialysis. CONCLUSIONS: A negative anion gap or an elevated serum chloride
      should prompt an evaluation for bromism. In this case hemodialysis dramatically
      improved the patient's clinical condition and reduced the half-life of bromide to
      1.38 h.

PMID- 9140330
TI  - Fatal bupropion overdose.
AB  - BACKGROUND: Bupropion is a unique monocyclic antidepressant that has been known
      to cause seizures in high therapeutic doses and in acute overdoses. Death due to
      ingestion, however, is a rare occurrence. CASE REPORT: We report a case of a 26
      year-old man who ingested 23 g bupropion, developed seizures and hypoxia, and
      presented in cardiac arrest. The patient was resuscitated in the emergency
      department, but died 4 d after supportive intensive care. CONCLUSIONS: Bupropion
      overdose may lead to recurrent seizures, hypoxia and death. Aggressive management
      of severe bupropion overdose is recommended.

PMID- 9140331
TI  - Heart donation after fatal acetaminophen poisoning.

PMID- 9140332
TI  - Impact of a worker's compensation practice guideline on lumbar spine fusion in
      Washington State.
AB  - OBJECTIVES: In the face of escalating medical costs for injured workers, the
      Washington State Department of Labor and Industries (L&I), which pays for most
      workers' compensation costs in the state, established guidelines for elective
      lumbar fusion as part of its inpatient utilization review program. The guidelines
      were tied to reimbursement strictures. The authors attempt to assess the effects
      of these guidelines, which were introduced in November 1988, upon subsequent L&I
      fusion procedures. METHODS: Discharge data from the Comprehensive Hospital
      Abstract Reporting System and algorithms using International Classification of
      Diseases, Version 9, Clinical Modification diagnosis and procedure codes were
      used to identify lumbar surgical cases. Population estimates were from the 1990
      US Census Bureau. RESULTS: During the period of years 1987 through 1992, the
      lumbar fusion rate for the state showed a 26% decline compared with a 3% decrease
      for all lumbar operations. After November 1988, when the guidelines went into
      effect, the state fusion rate declined 33%, whereas rates for nonfusion
      operations essentially were unchanged. The sharpest decline corresponded in time
      to implementation of the guidelines. Prior to the initiation of L&I guidelines,
      the proportion of fusions among L&I patients was higher than among non-L&I
      patients. The opposite was true by the end of 1992, and the L&I proportion
      decreased more rapidly than the non-L&I proportion. Time series analysis revealed
      that both the decline in Washington state lumbar fusion rates and the decline in
      the proportion of lumbar fusion among L&I patients were statistically
      significant. CONCLUSIONS: The data suggest that the L&I lumbar fusion surgery
      criteria and reimbursement standards implemented in 1988 contributed to a decline
      in rates of performing that procedure. The utilization review aspect of the
      guidelines as well as the process of involving surgeons in the preparation and
      dissemination of guidelines also may have been contributory.

PMID- 9140333
TI  - Expenditures on services for persons with acquired immunodeficiency syndrome
      under a Medicaid home and community-based waiver program. Are selection effects
      important?
AB  - OBJECTIVES: In 1990, the state of Florida implemented an acquired
      immunodeficiency syndrome (AIDS)-specific Medicaid waiver program to provide home
      and community-based services to AIDS patients as an alternative to institutional
      care. The program is available to Medicaid beneficiaries with AIDS who are at
      risk of institutionalization. This study examines whether the waiver option was
      effective in reducing Medicaid expenditures per beneficiary during its first 2
      years of operation. METHODS: The authors used Medicaid claims data and county
      information on the availability of health services to model the selection of the
      waiver option by AIDS patients and then to estimate the effect of the waiver on
      expenditures controlling for nonrandom program selection. RESULTS: The results
      indicate that the selection model is highly significant, but that the influence
      of nonrandom selection on the estimation of the program effects is negligible.
      More importantly, the regression results indicate that persons with AIDS who use
      waiver services incur monthly Medicaid expenditures that are on average 22% to
      27% lower than otherwise similar nonparticipants. CONCLUSIONS: These results,
      based on the first 2 years that Project AIDS Care was operational, suggest that
      home and community-based care for AIDS patients results in lower expenditures per
      beneficiary.

PMID- 9140334
TI  - The development of an instrument for assessing the quality of life of people with
      diabetes. Diabetes-39.
AB  - OBJECTIVES: The aim of this 2-year research project was to develop an instrument
      specifically designed to assess the quality of life of people with diabetes.
      METHODS: The project was divided into two phases. In the first phase, information
      from a detailed literature review, from existing quality-of-life instruments, and
      from interviews with health professionals and people with diabetes was used to
      develop an initial instrument of 92 items considered to address important aspects
      of patients' lives. This questionnaire was mailed to 1,000 people with diabetes,
      and data from the 516 respondents were used to select the most important and
      useful items. Fifty items were excluded, leaving 42 items that constituted the
      pilot instrument. During phase 2, the pilot instrument was used to assess the
      quality of life of 427 diabetic patients who completed the revised questionnaire.
      After analyzing this data, three additional items were dropped. The final
      instrument consists of 39 items and covers five dimensions of patients' lives:
      Energy and Mobility, Diabetes Control, Anxiety and Worry, Social Burden, and
      Sexual Functioning. RESULTS: The results of validity and reliability tests
      conducted to date testify to the relevance of the 39-item questionnaire (Diabetes
      39) as a valid discriminative instrument, one which shows significant
      correlations with an overall quality-of-life assessment, the pattern of diabetes
      severity, and comorbidity. Further, the results from Diabetes-39 correlate well
      with the results from the established generic quality-of-life instrument, the
      Medical Outcomes Study 36-Item Short-Form Health Survey. CONCLUSIONS: Validation
      of a quality-of-life instrument, however, is an ongoing process. Further research
      is required to corroborate these early findings and to ensure that this is an
      instrument that can capture data of greatest relevance to the diabetic patient
      and that is responsive to change in quality of life.

PMID- 9140335
TI  - Does fluoridation reduce the use of dental services among adults?
AB  - OBJECTIVES: The authors determine whether prevention influences the use of health
      services. Fluoridation's effect on restorative dental demand among 972 Washington
      state employees and spouses, aged 20 to 34 years, in two fluoridated communities
      and a nonfluoridated community was examined. METHODS: At baseline, adults were
      interviewed by telephone, and oral assessments were conducted to measure personal
      characteristics, lifetime exposure to fluoridated water, oral disease, and the
      quality of restorations. Adults were followed for 2 years to measure dental
      demand from dental claims. Each adult's baseline and claims data were linked with
      provider and practice variables collected from the dentist who provided
      treatment. RESULTS: Relative to adults with no lifetime exposure to fluoridated
      water, adults drinking fluoridated water for half or more of their lives had less
      disease at baseline and a lower but nonsignificant probability of receiving a
      restoration in the follow-up period. In the 2-year follow-up period, however,
      more than half of the restorations were performed to replace fillings of
      satisfactory or ideal quality at baseline. When only teeth with decay and
      unsatisfactory fillings at baseline were considered, adults with high
      fluoridation exposure had a lower probability of receiving a restoration than
      adults with no exposure. Market effects also were detected in demand equations;
      relative to adults in the nonfluoridated community, adults residing in the
      fluoridated community with a large dentist supply received a greater number of
      restorations, suggesting potential supplier-induced demand from less disease and
      fewer patients. CONCLUSIONS: Among adults aged 20 to 34 years with private dental
      insurance, fluoridation reduces oral disease but may or may not reduce use of
      restorative services, depending on dentists' clinical decisions.

PMID- 9140336
TI  - Technology coverage decisions by health care plans and considerations by medical
      directors.
AB  - OBJECTIVES: Decisions made by private health care plans as to whether to cover
      new medical technology have a significant impact on access, diffusion, and costs.
      This study describes the variation in health plan coverage of different laser
      technologies and the types of considerations used in making coverage decisions
      for them. METHODS: In a cross-sectional national survey of medical directors at
      private plans, medical directors indicated current coverage of 15 different laser
      therapies, and then ranked the top five considerations both in favor and against
      recommending coverage for three of the laser therapies (angioplasty, discectomy,
      and photodynamic therapy). The influence of explicit clinical information and/or
      plan characteristics on coverage and the importance of considerations was
      examined through multivariate analyses (multiple logistic or linear regression
      analysis). RESULTS: Overall, 231 medical directors responded from plans
      representing 66% and 72% of persons in US health maintenance organization and
      indemnity plans, respectively. Current coverage for 13 of the 15 laser therapies
      varied between 20% and 90%. For-profit and indemnity plans covered approximately
      two more of the different laser technologies than nonprofit plans and health
      maintenance organizations. Considerations most frequently listed in favor of and
      against recommending coverage across the three laser technologies were clinical,
      economic, and regulatory. Legal, competitive, and compassionate concerns were
      listed less frequently. Considerations were not uniform across laser therapies;
      they reflected the specifics of the technology under review. Plan characteristics
      influenced the ranking of considerations as well. For instance, health
      maintenance organizations were two to three times more likely than indemnity
      plans to list potential for decreased cost in favor of recommending coverage.
      CONCLUSIONS: These findings demonstrate that there is substantial variation in
      coverage of new technologies, indicating that a large proportion of the
      population covered by private health plans are ineligible for treatments that are
      routinely available to others. A greater range of medical therapy may be
      available for persons enrolled in indemnity and for-profit plans should their
      physicians choose to prescribe it. Clinical and economic considerations,
      including cost-effectiveness, predominate in coverage decisions for new
      technologies. The importance of considerations appears sensitive not only to
      specific clinical information, however, but also to characteristics of health
      plans.

PMID- 9140337
TI  - The use of significant others as proxy raters of the quality of life of patients
      with brain cancer.
AB  - OBJECTIVES: The use of self-report questionnaires for the assessment of health
      related quality of life (HRQOL) is increasingly common in clinical research. This
      method of data collection may be less suitable for patient groups who suffer from
      cognitive impairment, however, such as patients with brain cancer. In such cases,
      one can consider employing the patients' significant others as proxy raters of
      the patients' health-related quality of life. The authors examined the response
      agreement between patients with brain cancer and their significant others on a
      health-related quality of life instrument commonly used in cancer clinical
      trials, the EORTC QLQ-C30, and on a brain cancer-specific questionnaire module,
      the QLQ-BCM. METHODS: The study sample consisted of 103 pairs of patients, with
      either recently diagnosed or recurrent brain cancer, and their significant others
      (75% spouses, 22% relatives, and 3% friends). Patients and proxies independently
      completed the EORTC QLQ-C30 and the QLQ-BCM at three different times. RESULTS:
      Approximately 60% of the patient and proxy scores were in exact agreement, with
      more than 90% of scores being within one response category of each other. For
      most HRQOL dimensions assessed, moderate to good agreement was found.
      Statistically significant differences in mean scores were noted for several
      dimensions, with proxies tending to rate the patients as having a lower quality
      of life than the patients themselves. With the exception of fatigue ratings, this
      response bias was of a limited magnitude. Less agreement and a more pronounced
      response bias was observed for the more impaired patients, and particularly for
      patients exhibiting mental confusion. This finding was confirmed by longitudinal
      analyses, which indicated lower levels of patient-proxy agreement at follow-up
      for those patients whose physical or neurologic condition had deteriorated over
      time. CONCLUSIONS: In general, patients and their significant others provide
      similar ratings of the patients' quality of life. Lower levels of agreement and
      more biased ratings can be expected among those patients for whom the need for
      proxies is most salient. It is argued, however, that discrepancies between
      patient-proxy ratings should not be interpreted, a priori, as evidence of the
      inaccuracy or biased nature of proxy-generated data. Future studies are needed to
      examine the relative validity and reliability of patient-versus proxy-generated
      health-related quality of life scores.

PMID- 9140338
TI  - Time off work and the postpartum health of employed women.
AB  - OBJECTIVES: Parental and maternity leave policies are a popular fringe benefit
      among childbearing employed women and a benefit employers frequently are required
      to offer. However, few rigorous evaluations of the effect of maternal leave on
      maternal health exist. METHODS: Using a hybrid of the household and health
      production theories of Becker and Grossman and a sample of women identified from
      state vital statistics records, a nonlinear relationship between maternal
      postpartum health and time off work after childbirth was estimated. RESULTS: For
      women taking more than 12 weeks leave, time off work had a positive effect on
      vitality. With more than 15 weeks leave, time off work had a positive effect on
      maternal, mental health, and with more than 20 weeks leave, time off work had a
      positive effect on role function. Subjects' mental health scores were comparable
      and vitality scores slightly lower than age- and gender-specific norms; 70% of
      women studied reported role function limitations. CONCLUSIONS: Findings suggest
      employed women experience problems in well-being at approximately seven months
      postpartum. Variables associated with improved health include: longer maternity
      leaves, fewer prenatal mental health symptoms, fewer concurrent physical
      symptoms, more sleep, increased social support, increased job satisfaction, less
      physical exertion on the job, fewer infant symptoms, and less difficulty
      arranging child care.

PMID- 9140339
TI  - An empirical comparison of four generic health status measures. The Nottingham
      Health Profile, the Medical Outcomes Study 36-item Short-Form Health Survey, the
      COOP/WONCA charts, and the EuroQol instrument.
AB  - OBJECTIVES: An empirical, head-to-head comparison of the performance
      characteristics of four generic health status measures. METHODS: The Nottingham
      Health Profile, the Medical Outcomes Study 36-item Short-Form Health Survey (SF
      36), the COOP/WONCA charts, and the EuroQol instrument were simultaneously
      employed in a controlled survey measuring the impact of migraine on health
      status. The feasibility (number of missing cases per item), internal consistency
      (Cronbach's alpha), construct validity (correlation patterns and common factor
      analysis), and discriminative ability (Receiver Operating Characteristics
      analyses) of the four measures were investigated. RESULTS: The Nottingham Health
      Profile produced the lowest missing value rate. The internal consistency of the
      Nottingham Health Profile scales was lower than the scales of the SF-36. Combined
      factor analyses with data of the four instruments together resulted in two-factor
      solutions with a physical and a mental factor, explaining approximately 50% of
      variance. The SF-36 exhibited the best ability to discriminate between groups.
      Test-retest reliability and sensitivity to change over time could not be tested
      because of the cross-sectional character of the study. CONCLUSIONS: None of the
      instruments performed uniformly as "best" or "worst." Purely on the basis of the
      results of the psychometric analyses, the SF-36 appeared to be the most suitable
      measure of health status in this relatively healthy population. In general, the
      choice of the most suitable instrument for generic health status assessment in a
      particular study should be guided by the special features of each candidate
      instrument under consideration.

PMID- 9140340
TI  - Salt intake, cardiovascular disease and public health.

PMID- 9140341
TI  - Estimating the risks of cardiac surgery.

PMID- 9140342
TI  - Meeting the challenge of adolescent mental health.

PMID- 9140343
TI  - Secondary adrenocortical insufficiency: avoiding potentially fatal pitfalls in
      diagnosis and treatment.

PMID- 9140344
TI  - The Hobart Salt Study 1995: few meet national sodium intake target.
AB  - OBJECTIVE: To estimate 24-hour sodium and potassium excretion in an urban
      Australian population. DESIGN AND SETTING: Cross-sectional survey of an urban
      population in Hobart, Tasmania, in 1995. PARTICIPANTS: Systematic sample (87 men,
      107 women) from the Commonwealth Electoral Roll of people aged 18-70 years on 30
      June 1995 whose residential address was within 10 km of the Hobart General Post
      Office. MAIN OUTCOME MEASURE: Conformity with the national target for sodium
      intake for the year 2000 of < or = 100 mmol/day. RESULTS: The target was met by
      6% of men and 36% of women. This difference between the sexes was significant (P
      < 0.001), while differences between age groups and socioeconomic levels were not
      significant. CONCLUSION: Our findings confirm the low level of conformity with
      the national sodium target reported by the handful of Australian studies over the
      past decade. Given the major community costs associated with hypertension, our
      results highlight the need for effective and properly monitored action to reduce
      sodium intakes.

PMID- 9140346
TI  - Malnutrition and microcephaly in Australian aboriginal children.
AB  - OBJECTIVE: To examine the association between malnutrition and microcephaly in
      the first two years of life. DESIGN: Cross-sectional study. SETTING AND
      PARTICIPANTS: Royal Darwin Hospital (a tertiary referral centre); 157 of 165
      previously studied Aboriginal children aged under two years who were admitted
      with diarrhoea between May 1990 and April 1991. Birth weight, birth length, birth
      head circumference, admission head circumference and admission nutritional status
      were examined. Nutritional status was categorised according to World Health
      Organization (WHO) criteria for wasting (thinness) and stunting (shortness).
      Microcephaly on admission was defined as a head circumference less than the
      second percentile on Australian reference charts. Small-for-gestational-age (SGA)
      and birth microcephaly were defined as being less than the tenth percentile for
      an Australian hospitalised population, corrected for gestational age at
      confinement. Low birth weight (LBW) was defined as less than 2500 g. MAIN OUTCOME
      MEASURE: Microcephaly on admission. RESULTS: Of the 157 children, 76 (48%) were
      wasted, 36 (23%) stunted and 37 (24%) microcephalic on admission. A total of 26
      (17%) children had been of LBW, 17 (11%) SGA and 21 (13%) microcephalic at birth.
      On univariate analysis, microcephaly on admission was associated with wasting
      (crude odds ratio [OR], 3.91; 95% confidence interval [CI], 1.6-9.7; P < 0.005),
      but not stunting. There were no significant associations between microcephaly on
      admission and LBW, being SGA, microcephaly at birth, age or sex. With
      multivariate analysis, birth head circumference was significantly associated with
      microcephaly on admission (adjusted OR, 3.62; 95% CI, 1.28-10.23; P < 0.05), as
      was wasting (adjusted OR, 4.38; 95% CI, 1.88-10.20; P < 0.001). CONCLUSIONS:
      Wasting was significantly associated with microcephaly, independent of
      intrauterine growth retardation (as measured by being SGA) and LBW. As
      malnutrition in critical periods of both intra- and extrauterine development may
      have irreversible effects on intellectual potential and behaviour, the emphasis
      on improved nutrition must begin during pregnancy, and should continue in infancy
      and early childhood.

PMID- 9140345
TI  - Risk prediction in coronary artery surgery: a comparison of four risk scores.
AB  - OBJECTIVE: To determine which of four proposed risk scores best predicts
      immediate outcome of cardiac surgery. DESIGN: Observational cohort study.
      SETTING: Sir Charles Gairdner Hospital (a university teaching hospital), Perth,
      Western Australia, 18 March 1993 to 5 March 1996. SUBJECTS: 927 consecutive
      patients undergoing surgery for coronary artery disease. OUTCOME MEASURES:
      Patient risk scores (by methods of Parsonnet et al., Higgins et al., Tremblay et
      al. and Tu et al.); in-hospital mortality; postoperative hospital stay > 14 days;
      receiver operating characteristic (ROC) curves comparing sensitivity and
      specificity in predicting adverse outcomes for each risk score. RESULTS: In
      hospital mortality rate was 3.5% and mean postoperative hospital stay was 10.7
      days. The four scores had similar predictive abilities, with mean areas under the
      ROC curves (95% confidence intervals) for mortality and postoperative stay > 14
      days, respectively: 0.70 (0.62-0.78) and 0.70 (0.65-0.75) for the Parsonnet
      score; 0.68 (0.59-0.77) and 0.70 (0.64-0.75) for the Higgins score; 0.68 (0.59
      0.77) and 0.67 (0.62-0.73) for the Tremblay score; and 0.68 (0.60-0.76) and 0.69
      (0.64-0.75) for the Tu score. CONCLUSION: Any of the scores may be used to
      estimate perioperative risk and to compare outcome between coronary surgery
      units, but none has sufficient specificity and sensitivity to identify specific
      individuals who will experience an adverse outcome. Further development of risk
      assessment is needed before adverse outcome can be accurately predicted in
      cardiac surgical patients.

PMID- 9140347
TI  - Severe falciparum malaria with hyperparasitaemia treated with intravenous
      artesunate.
AB  - We report a 57-year-old man with falciparum malaria contracted in Kenya who
      presented with a three-day history of symptoms. Despite prompt treatment with
      quinine and artesunate and rapid clearing of the parasitaemia, he developed
      multiple complications and died 28 days after presentation. This case illustrates
      the potential for malaria to be fatal despite appropriate treatment and is one of
      the first reports of the use of artesunate in a hospital in a developed country.

PMID- 9140348
TI  - Thrombolytic therapy in acute ischaemic stroke: the jury needs more evidence.
AB  - Randomised controlled trials have shown that thrombolytic therapy for acute
      ischaemic stroke may reduce the rate of death and disability at three- or six
      month follow-up, but may also increase the risk of haemorrhage and early death.
      Probable predictors of increased risk are severe neurological deficit and early
      signs of infarction on computed tomography, but these remain to be confirmed.
      More research is needed to determine which stroke patients will benefit from
      thrombolysis and the best regimen to use.

PMID- 9140349
TI  - Psychosocial disorders in young people: on the agenda but not on the mend.

PMID- 9140350
TI  - History in the making: the evolution of consumer product information (CPI)

PMID- 9140351
TI  - Ancillary services in rheumatology.

PMID- 9140352
TI  - Autism: time for a national approach to early assessment and management.

PMID- 9140353
TI  - Autism: time for a national approach to early assessment and management.

PMID- 9140354
TI  - Pentoxifylline to treat Mycobacterium avium complex exacerbation in late-stage
      HIV infection.

PMID- 9140355
TI  - Evaluation of the neonatal hepatitis B vaccination program in infants born to
      Chinese mothers.

PMID- 9140356
TI  - Drug use in nursing homes: some new evidence.

PMID- 9140357
TI  - Case survey of management of cellulitis in a tertiary teaching hospital.

PMID- 9140358
TI  - Raynaud's phenomenon of the nipple: a preventable cause of breastfeeding failure?

PMID- 9140359
TI  - Interhemispheric differences of hand muscle representation in human motor cortex.
AB  - Focal magnetic transcranial stimulation (TCS) is employed for mapping of the
      motor cortical output to abductor digiti minimi (ADM) muscle. The aim of this
      study was to evaluate the interhemispheric asymmetries in normals. Motor maps
      were obtained through motor evoked potentials (MEPs) recordings from ADM muscle
      in 20 healthy subjects in right and left hemispheres TCS. Measurement of several
      indexes such as excitability threshold, MEPs amplitude, MEPs latency, and silent
      period duration did not show differences between the hemispheres. Moreover, no
      interhemispheric asymmetries were found when the amplitude ratio values were
      analyzed. The hand motor cortical area, as represented by the number of
      responsive sites (3.6 vs. 3.5) and the "hot spot" site localization presented a
      fairly symmetrical organization. Absolute values displayed a relatively wide
      intersubject variability, while their interhemispheric differences were extremely
      restricted. This observation can offer a new tool in diagnosing and following up
      neurological disorders affecting the central motor system, mainly for those
      concerning monohemispheric lesions.

PMID- 9140360
TI  - Cytokines and the pathogenesis of myasthenia gravis.
AB  - Myasthenia gravis (MG) and its animal model experimental autoimmune myasthenia
      gravis (EAMG) are caused by autoantibodies against nicotinic acetylcholine
      receptor (AChR) in skeletal muscle. The production of anti-AChR antibodies is
      mediated by cytokines produced by CD4+ and CD8+ T helper (Th) cells. Emerging
      investigations of the roles of cytokines in MG and EAMG have revealed that the
      Th2 cell related cytokine interleukin 4 (IL-4), an efficient growth promoter for
      B-cell proliferation and differentiation, is important for anti-AChR antibody
      production. IL-6 and IL-10 have similar effects. The Th1 cytokine IFN-gamma is
      important in inducing B-cell maturation and in helping anti-AChR antibody
      production and, thereby, for induction of clinical signs and symptoms. Results
      from studies of time kinetics of cytokines imply that IFN-gamma is more agile at
      the onset of EAMG, probably being one of the initiating factors in the induction
      of the disease, and IL-4 may be mainly responsible for disease progression and
      persistance. Even though other Th1 cytokines like IL-2, tumor necrosis factor
      alpha (TNF-alpha), and TNF-beta as well as the cytolytic compound perforin do not
      directly play a role in T-cell-mediated help for anti-AChR antibody production,
      they are actually involved in the development of both EAMG and MG, probably by
      acting in concert with other cytokines within the cytokine network. In contrast,
      transforming growth factor beta (TGF-beta) exerts immunosuppressive effects which
      include the down-regulation of both Th1 and Th2 cytokines in MG as well as EAMG.
      Suppressive effects are also exerted by interferon alpha (IFN-alpha). Based on
      elucidation of the role of cytokines in EAMG and MG, treatments that up-modulate
      TGF-beta or IFN-alpha and/or suppress cytokines that help B-cell proliferation
      could be useful to improve the clinical outcome.

PMID- 9140361
TI  - Validity of electromyograms and tension as a means of motor unit number
      estimation.
AB  - The purpose of this study was to validate three different techniques for
      obtaining motor unit number estimates of the rat medial gastrocnemius muscle.
      These consisted of two electromyographic techniques using unprocessed and
      digitally averaged unitary muscle action potentials, and one mechanical
      technique. We also injected subunit B of cholera toxin into this muscle and
      counted the number of spinal motor neurons labeled by the toxin. Our results
      revealed that a motor unit number estimate obtained by using the unprocessed
      unitary muscle action potential was statistically different from the actual
      number of motor neurons. The other two motor unit number estimates, however, were
      not statistically different from the actual motor neuron number. These two
      methods thus seem more appropriate than the first electromyographic method for
      obtaining an accurate motor unit number estimate.

PMID- 9140362
TI  - Sequential muscle biopsy changes in a case of congenital myopathy.
AB  - Muscle biopsies at age 7 months in a set of dizygotic male twins born floppy
      showed typical features of congenital fiber-type disproportion (CFTD). One of the
      twins died at age 1 year due to respiratory complications. The second one
      subsequently developed facial diplegia and external ophthalmoplegia. He never
      walked, remained wheelchair bound, and required continuous ventilatory support.
      He underwent repeat biopsies at ages 2 and 4, which showed many atrophic type 1
      muscle fibers containing central nuclei and severe type 2 fiber deficiency
      compatible with centronuclear myopathy (CNM). Two-dimensional gel electrophoresis
      of muscle showed decreases of type II myosin light chains 2 and 3, suggestive of
      histochemical type I fiber deficiency. The progressive nature of morphological
      changes in one of our patients cannot be explained by maturational arrest. Repeat
      biopsies in cases of CFTD with rapid clinical deterioration may very well show
      CNM.

PMID- 9140363
TI  - Corticomotor threshold to magnetic stimulation: normal values and repeatability.
AB  - The threshold for corticomotor excitation by magnetic stimuli is a clinically
      important parameter in the assessment of central motor conduction. Hitherto,
      arbitrary criteria have been adopted to define threshold and there are few
      published data using a figure of eight coil. A new method is described in which
      the highest stimulus intensity evoking responses in the relaxed first dorsal
      interosseous muscle with a probability of zero [lower threshold (LT)] and the
      lowest intensity evoking responses with a probability of one [upper threshold
      (UT)] have been determined. The method, which utilizes a coil located and
      optimally oriented over hand motor cortex, minimizes the number of stimuli
      needed. Both LT and UT are normally distributed and are independent of age,
      gender, and hemisphere. In 102 healthy hands of 55 control subjects 23-84 years
      of age, mean +/- SD UT was 46.6 +/- 9.4% and LT was 38.0 +/- 8.6% maximum
      stimulator output. Repeatability estimates indicated an absolute change of more
      than 13% or 11% in UT or LT respectively in the same individual over 1-3 months
      was significant at the 5% level.

PMID- 9140364
TI  - Nonenzymatic glycation of peripheral and central nervous system proteins in
      experimental diabetes mellitus.
AB  - Nonenzymatic glycation of neural proteins could underlie diabetic peripheral
      neuropathy. Cytoskeletal and myelin protein fractions of central nervous system
      and peripheral nervous system (PNS) tissue from rats with streptozotocin-induced
      diabetes of 1.5 and 8 months duration were analyzed for glycation products. In
      sciatic nerve cytoskeletal preparations from both diabetic and control animals we
      found high levels of the early glycation product (measured as furosine) after 6
      weeks, which had fallen markedly by 8 months. Conversely the advanced glycation
      end product (AGE), pentosidine, was low at 6 weeks and high by 8 months in
      diabetic animals. The levels of glycation products were much lower in spinal cord
      and spinal nerve from diabetic animals. There was increased borotritride labeling
      of neurofilament subunits, and of cross-linked material, in cytoskeletal
      fractions of diabetic sciatic nerves. These results show that the PNS
      cytoskeleton is vulnerable to nonenzymatic glycation, resulting in AGE formation,
      in diabetic rats and to a lesser extent in normals.

PMID- 9140365
TI  - Satellite potentials as a measure of neuromuscular disorders.
AB  - The study was carried out to investigate the characteristics of satellite
      potentials and their validity in clinical electromyography. Conventional needle
      electromyography was applied to the right biceps brachii and tibialis anterior
      muscles of 41 controls, 22 neuropathies, and 17 myopathies. Satellites were
      defined as small extrapotentials, preceding/following the main motor unit action
      potential (MUAP) component and separated from it by an isoelectrical interval of
      > 1 ms. The normal mean satellite rate was 1.6% (biceps brachii) and 1.2%
      (tibialis anterior). In the biceps brachii (tibialis anterior) muscle it was 5
      (5) times higher for neuropathies (P = 0.005, P = 0.006) and 5 (6) times higher
      for myopathies (P = 0.006, P = 0.003). MUAP parameters were not significantly
      different, whether satellites were considered or ignored. Evaluation of the
      satellite rate increased detection rates of neuromuscular disorders by up to 13%.
      The satellite rate proved a valuable and easily available, supplemental
      electromyographic parameter for the discrimination and detection of neuromuscular
      disorders.

PMID- 9140366
TI  - Treatment of occupational cramp with botulinum toxin: diffusion of toxin to
      adjacent noninjected muscles.
AB  - Over a 5-year period, 40 patients, 11 with musician's and 29 with writer's cramp,
      were treated with botulinum toxin A using a precise injection technique in which
      the hollow-bore electromyography (EMG) needle was positioned by both standard EMG
      and by muscle twitch evoked by stimulating current passed through it. Moderate to
      complete improvement in dystonia occurred in 28 patients (70%) after the first
      injection and in 34 patients (85%) after the second injection with better outcome
      in nonmusicians than in musicians. Of note, weakness of uninjected muscles,
      immediately adjacent to those injected, was found in 25/40 patients (63%). The
      most common patterns of toxin spread were from flexor digitorum sublimis to
      profundus, extensor carpi radialis to extensor digitorum communis, and extensor
      indicis proprius to extensor pollicis brevis. Spread to, and weakness of,
      adjacent uninjected muscles was a major factor contributing to suboptimal outcome
      in 6/39 (15%) such patients.

PMID- 9140368
TI  - Dissociated changes in fatigue resistance and characteristics of M waves and
      twitches in a fast muscle group after two weeks of chronic stimulation: influence
      of the stimulation patterns.

PMID- 9140367
TI  - Familial limb-girdle myasthenia with tubular aggregates.
AB  - Two sisters developed slowly progressive limb-girdle weakness in their childhood.
      The weakness responded to acetylcholinesterase inhibitors. Repetitive nerve
      stimulation showed decremental responses and single-fiber electromyography
      demonstrated increased jitter and blocking. Needle electromyography revealed
      myopathic changes. Antiacetylcholine receptor antibodies were negative.
      Histologic examinations demonstrated myopathy with tubular aggregates in the
      muscle fibers while the neuromuscular junctions appeared normal. They were
      diagnosed with familial limb-girdle myasthenia. This is the first report of this
      syndrome with morphologic studies of neuromuscular junctions.

PMID- 9140369
TI  - Two siblings with nerve conduction abnormalities indicating an acquired type of
      demyelinating neuropathy.

PMID- 9140370
TI  - Truncal sensory loss in acquired demyelinating neuropathies.

PMID- 9140371
TI  - Treatment of Lambert-Eaton syndrome with intravenous immunoglobulin.

PMID- 9140372
TI  - Bilateral bulbocavernosus reflexes: crossing of nerve pathways or artifact?

PMID- 9140373
TI  - Inflammatory myopathy after intravenous streptokinase.

PMID- 9140374
TI  - Differences in CTG triplet repeat expansions in an ovarian cancer and cyst from a
      patient with myotonic dystrophy.

PMID- 9140376
TI  - Stimulus-induced repetitive discharge of long latency.

PMID- 9140375
TI  - Characteristic morphologic manifestation of CADASIL, cerebral autosomal-dominant
      arteriopathy with subcortical infarcts and leukoencephalopathy, in skeletal
      muscle and skin.

PMID- 9140377
TI  - Ulnar innervation of the thenar eminence with preservation of median innervation
      of first lumbrical muscle.

PMID- 9140378
TI  - Paget's disease of bone and motor neuron disease.

PMID- 9140379
TI  - Unmasking and exacerbation of myasthenia gravis by ophthalmic solutions:
      betoxolol, tobramycin, and dexamethasone. A case report.

PMID- 9140380
TI  - One for the vine.

PMID- 9140381
TI  - Growing interest in Turner syndrome.

PMID- 9140382
TI  - Elegant nose and powerful body--who were the parents of such nobility?

PMID- 9140383
TI  - LINEs and Alus--the polyA connection.

PMID- 9140384
TI  - Simple minded mice from 'in vivo' libraries.

PMID- 9140385
TI  - beta-Catenin--one player, two games.

PMID- 9140386
TI  - Inside out, boy you turn me?

PMID- 9140387
TI  - A dominant-negative mutation of the growth hormone receptor causes familial short
      stature.

PMID- 9140388
TI  - Intelligent linkage analysis using gene density estimates.

PMID- 9140389
TI  - Methylation-specific PCR simplifies imprinting analysis.

PMID- 9140390
TI  - Germline BRCA2 6174delT mutations in Ashkenazi Jewish pancreatic cancer patients.

PMID- 9140391
TI  - Genetic variation among 129 substrains and its importance for targeted
      mutagenesis in mice.
AB  - Targeted mutagenesis in mice, a powerful tool for the analysis of gene function
      and human disease, makes extensive use of 129 mouse substrains. Although all are
      named 129, we document that outcrossing of these substrains, both deliberate and
      accidental, has lead to extensive genetic variability among substrains and
      embryonic stem cells derived from them. This clearer understanding of 129
      substrain variability allows consideration of its negative impact on targeting
      technology, including: homologous recombination frequencies, preparation of
      inbred animals, and availability of appropriate controls. Based on these
      considerations we suggest a number of recommendations for future experimental
      design.

PMID- 9140392
TI  - Functional screening of 2 Mb of human chromosome 21q22.2 in transgenic mice
      implicates minibrain in learning defects associated with Down syndrome.
AB  - Using Down syndrome as a model for complex trait analysis, we sought to identify
      loci from chromosome 21q22.2 which, when present in an extra dose, contribute to
      learning abnormalities. We generated low-copy-number transgenic mice, containing
      four different yeast artificial chromosomes (YACs) that together cover
      approximately 2 megabases (Mb) of contiguous DNA from 21q22.2. We subjected
      independent lines derived from each of these YAC transgenes to a series of
      behavioural and learning assays. Two of the four YACs caused defects in learning
      and memory in the transgenic animals, while the other two YACs had no effect. The
      most severe defects were caused by a 570-kb YAC; the interval responsible for
      these defects was narrowed to a 180-kb critical region as a consequence of YAC
      fragmentation. This region contains the human homologue of a Drosophila gene,
      minibrain, and strongly implicates it in learning defects associated with Down
      syndrome.

PMID- 9140393
TI  - Many human L1 elements are capable of retrotransposition.
AB  - Using a selective screening strategy to enrich for active L1 elements, we
      isolated 13 full-length elements from a human genomic library. We tested these
      and two previously-isolated L1s (L1.3 and L1.4) for reverse transcriptase (RT)
      activity and the ability to retrotranspose in HeLa cells. Of the 13 newly
      isolated L1s, eight had RT activity and three were able to retrotranspose. L1.3
      and L1.4 possessed RT activity and retrotransposed at remarkably high
      frequencies. These studies bring the number of characterized active human L1
      elements to seven. Based on these and other data, we estimate that 30-60 active
      L1 elements reside in the average diploid genome.

PMID- 9140394
TI  - HIP1, a human homologue of S. cerevisiae Sla2p, interacts with membrane
      associated huntingtin in the brain.
AB  - Huntington disease (HD) is associated with the expansion of a polyglutamine
      tract, greater than 35 repeats, in the HD gene product, huntingtin. Here we
      describe a novel huntingtin interacting protein, HIP1, which co-localizes with
      huntingtin and shares sequence homology and biochemical characteristics with
      Sla2p, a protein essential for function of the cytoskeleton in Saccharomyces
      cerevisiae. The huntingtin-HIP1 interaction is restricted to the brain and is
      inversely correlated to the polyglutamine length in huntingtin. This provides the
      first molecular link between huntingtin and the neuronal cytoskeleton and
      suggests that, in HD, loss of normal huntingtin-HIP1 interaction may contribute
      to a defect in membrane-cytoskeletal integrity in the brain.

PMID- 9140395
TI  - Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure
      in idiopathic short stature and Turner syndrome.
AB  - Growth retardation resulting in short stature is a major concern for parents and
      due to its great variety of causes, a complex diagnostic challenge for
      clinicians. A major locus involved in linear growth has been implicated within
      the pseudoautosomal region (PAR1) of the human sex chromosomes. We have
      determined an interval of 170 kb of DNA within PAR1 which was deleted in 36
      individuals with short stature and different rearrangements on Xp22 or Yp11.3.
      This deletion was not detected in any of the relatives with normal stature or in
      a further 30 individuals with rearrangements on Xp22 or Yp11.3 with normal
      height. We have isolated a homeobox-containing gene (SHOX) from this region,
      which has at least two alternatively spliced forms, encoding proteins with
      different patterns of expression. We also identified one functionally significant
      SHOX mutation by screening 91 individuals with idiopathic short stature. Our data
      suggest an involvement of SHOX in idiopathic growth retardation and in the short
      stature phenotype of Turner syndrome patients.

PMID- 9140396
TI  - Germline mutations of the PTEN gene in Cowden disease, an inherited breast and
      thyroid cancer syndrome.
AB  - Cowden disease (CD) is an autosomal dominant cancer predisposition syndrome
      associated with an elevated risk for tumours of the breast, thyroid and skin.
      Lhermitte-Duclos disease (LDD) cosegregates with a subset of CD families and is
      associated with macrocephaly, ataxia and dysplastic cerebellar
      gangliocytomatosis. The common feature of these diseases is a predisposition to
      hamartomas, benign tumours containing differentiated but disorganized cells
      indigenous to the tissue of origin. Linkage analysis has determined that a single
      locus within chromosome 10q23 is likely to be responsible for both of these
      diseases. A candidate tumour suppressor gene (PTEN) within this region is mutated
      in sporadic brain, breast and prostate cancer. Another group has independently
      isolated the same gene, termed MMAC1, and also found somatic mutations throughout
      the gene in advanced sporadic cancers. Mutational analysis of PTEN in CD kindreds
      has identified germline mutations in four of five families. We found nonsense and
      missense mutations that are predicted to disrupt the protein tyrosine/dual
      specificity phosphatase domain of this gene. Thus, PTEN appears to behave as a
      tumour suppressor gene in the germline. Our data also imply that PTEN may play a
      role in organizing the relationship of different cell types within an organ
      during development.

PMID- 9140397
TI  - Germline and somatic mutations in the tyrosine kinase domain of the MET proto
      oncogene in papillary renal carcinomas.
AB  - Hereditary papillary renal carcinoma (HPRC) is a recently recognized form of
      inherited kidney cancer characterized by a predisposition to develop multiple,
      bilateral papillary renal tumours. The pattern of inheritance of HPRC is
      consistent with autosomal dominant transmission with reduced penetrance. HPRC is
      histologically and genetically distinct from two other causes of inherited renal
      carcinoma, von Hippel-Lindau disease (VHL) and the chromosome translocation
      (3;8). Malignant papillary renal carcinomas are characterized by trisomy of
      chromosomes 7, 16 and 17, and in men, by loss of the Y chromosome. Inherited and
      sporadic clear cell renal carcinomas are characterized by inactivation of both
      copies of the VHL gene by mutation, and/or by hypermethylation. We found that the
      HPRC gene was located at chromosome 7q31.1-34 in a 27-centimorgan (cM) interval
      between D7S496 and D7S1837. We identified missense mutations located in the
      tyrosine kinase domain of the MET gene in the germline of affected members of
      HPRC families and in a subset of sporadic papillary renal carcinomas. Three
      mutations in the MET gene are located in codons that are homologous to those in c
      kit and RET, proto-oncogenes that are targets of naturally-occurring mutations.
      The results suggest that missense mutations located in the MET proto-oncogene
      lead to constitutive activation of the MET protein and papillary renal
      carcinomas.

PMID- 9140399
TI  - Organization of the Fugu rubripes Hox clusters: evidence for continuing evolution
      of vertebrate Hox complexes.
AB  - The clustered organization of Hox genes provides a powerful opportunity to
      examine gene gain and loss in evolution because physical linkage is a key
      diagnostic feature which allows homology to be established unambiguously.
      Furthermore, Hox genes play a key role in determination of axial and appendicular
      skeletal morphology and may be a key component of the evolution of diverse
      metazoan body forms. Despite suggestions that changes in Hox gene number played a
      role in evolution of metazoan body plans, there has been a general lack of
      evidence for such variation amongst gnathostomes (or indeed any vertebrate) and
      it has therefore been widely assumed that differential regulation may be the key
      element in all vertebrate Hox evolution. We have studied the Hox gene clusters of
      a teleost fish, Fugu rubripes, to test the possibility that Hox organization may
      have varied since the origin of jawed vertebrates. We have identified four Hox
      complexes in Fugu and found an unprecedented degree of variation when compared
      with tetrapod clusters. Our data show that: Fugu clusters are widely variant with
      respect to length; at least nine genes have been lost; there is a new group-2
      paralogue; and pseudo-gene remnants of group-1 and group-3 paralogues were found
      in the Hoxc complex, when compared with the present mammalian clusters. We show
      that gene loss after duplication of the prototypical vertebrate Hox clusters is a
      key feature of both tetrapod and fish evolution.

PMID- 9140398
TI  - Chemotherapy induces transient sex chromosomal and autosomal aneuploidy in human
      sperm.
AB  - Each year more than 20,000 children and young persons of reproductive age are
      exposed to known mutagens in the form of chemo- and/or radiotherapy for cancer in
      the States. As more of these treatments are effective there is growing concern
      that genetic defects are introduced in the germ cells of these young patients. It
      is well documented for male rodents that treatment with chemo- and radio
      therapeutic agents before mating can cause genetic damage in the germ line, and
      the magnitude of heritable effects depends on the spermatogenic cell stage
      treated. Similar germinal effects are suspected to occur in humans but remain
      unproven. Hodgkin's disease (HD) is an example of a malignancy which is typically
      diagnosed during a patient's reproductive years. In our study we observed eight
      male HD patients who were treated with NOVP (Novanthrone, Oncovin, Vinblastine,
      Prednisone) chemotherapy. We evaluated sperm aneuploidy using multi-colour
      fluorescence in situ hybridization (FISH), and found approximately 5-fold
      increases in sperm with disomies, diploidies and complex genotypes involving
      chromosome X, Y and 8. Increases in sex chromosome aneuploidies arose from
      segregation errors at meiosis I as well as meiosis II. The aneuploidy effects
      were transient, however, declining to pretreatment levels within approximately
      100 days after the end of the therapy. When compared with normal men, some HD
      patients showed higher proportions of certain sperm aneuploidy types even before
      their first therapy.

PMID- 9140400
TI  - The parentage of a classic wine grape, Cabernet Sauvignon.
AB  - The world's great wines are produced from a relatively small number of classic
      European cultivars of Vitis vinifera L Most are thought to be centuries old and
      their origins have long been the subject of speculation. Among the most prominent
      of these cultivars is Cabernet Sauvignon, described as "the world's most renowned
      grape variety for the production of fine red wine". Although now grown in many
      countries, Cabernet Sauvignon derives its fame from its long association with the
      Bordeaux region of France, where it has been grown at least since the 17th
      century. We present microsatellite DNA evidence for the hypothesis that Cabernet
      Sauvignon is the progeny of two other Bordeaux cultivars, Cabernet franc and
      Sauvignon blanc. Likelihood ratios support this hypothesis to a very high degree
      of probability. A close relationship between Cabernet Sauvignon and Cabernet
      franc has been suspected but the genetic contribution of Sauvignon blanc, despite
      its similar name, is a surprise.

PMID- 9140402
TI  - Tissue-specific selection for different mtDNA genotypes in heteroplasmic mice.
AB  - Mammalian mitochondrial DNA (mtDNA) is a highly polymorphic, high-copy-number
      genome that is maternally inherited. New mutations in mtDNA segregate rapidly in
      the female germline due to a genetic bottleneck in early oogenesis and as a
      result most individuals are homoplasmic for a single species of mtDNA. Sequence
      variants thus accumulate along maternal lineages without genetic recombination.
      Most of the extant variation in mtDNA in mammalian populations has been assumed
      to be neutral with respect to selection; however, comparisons of the ratio of
      replacement to silent nucleotide substitutions between species suggest that the
      evolution of mammalian mtDNA is not strictly neutral. To test directly whether
      polymorphic mtDNAs behave as neutral variants, we examined the segregation of two
      different mtDNA genotypes in the tissues of heteroplasmic mice. We find evidence
      for random genetic drift in some tissues, but in others strong, tissue-specific
      and age-related, directional selection for different mtDNA genotypes in the same
      animal. These surprising data suggest that the coding sequence of mtDNA may
      represent a compromise between the competing demands of different tissues and
      point to the existence of unknown, tissue-specific nuclear genes important in the
      interaction between the nuclear and mitochondrial genomes.

PMID- 9140401
TI  - Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate
      deficient glycoprotein type I syndrome (Jaeken syndrome).
AB  - Carbohydrate-deficient glycoprotein syndrome type 1 (CDG1 or Jaeken syndrome) is
      the prototype of a class of genetic multisystem disorders characterized by
      defective glycosylation of glycoconjugates. It is mostly a severe disorder which
      presents neonatally. There is a severe encephalopathy with axial hypotonia,
      abnormal eye movements and pronounced psychomotor retardation, as well as a
      peripheral neuropathy, cerebellar hypoplasia and retinitis pigmentosa. The
      patients show a peculiar distribution of subcutaneous fat, nipple retraction and
      hypogonadism. There is a 20% lethality in the first years of life due to severe
      infections, liver insufficiency or cardiomyopathy. CDG1 shows an autosomal
      recessive mode of inheritance and has been mapped to chromosome 16p. Most
      patients show a deficiency of phosphomannomutase (PMM)8, an enzyme necessary for
      the synthesis of GDP-mannose. We have cloned the PMM1 gene, which is on
      chromosome 22q13 (ref.9). We now report the identification of a second human PMM
      gene, PMM2, which is located on 16p13 and which encodes a protein with 66%
      identity to PMM1. We found eleven different missense mutations in PMM2 in 16 CDG1
      patients from different geographical origins and with a documented
      phosphomannomutase deficiency. Our results give conclusive support to the
      biochemical finding that the phosphomannomutase deficiency is the basis for CDG1.

PMID- 9140403
TI  - Emerin deletion reveals a common X-chromosome inversion mediated by inverted
      repeats.
AB  - Emery-Dreifuss muscular dystrophy (EMD) is an X-linked disorder characterized by
      contractures, progressive muscle weakness and cardiomyopathy. The emerin gene,
      located in human Xq28, is approximately 2 kb in length, is composed of 6 exons
      and falls within a 219-kb region that has been completely sequenced. Immediately
      centromeric to emerin is the 26-kb filamin gene (FLN1), composed of 48 exons and
      encoding the actin-binding protein 280 (refs 7,8). Flanking this 48-kb
      FLN1/emerin region are two large inverted repeats, each 11.3 kb, that exhibit >
      99% sequence identity. The high level of genomic detail in this region allowed us
      to characterize the first complete emerin gene deletion mutation that also
      involved a partial duplication of the nearby FLN1 gene. This rearrangement could
      be explained by mispairing of the large inverted repeats, followed by double
      recombination among one set of mispaired repeats and internal sequences.
      Furthermore, our characterization of this rare DNA rearrangement revealed a more
      common result of the mispairing of these large inverted repeats--recombination
      contained within the inverted repeats leading to the maintenance of repeat
      sequence homogeneity and inversion of the 48-kb FLN1/emerin region. The presence
      of this frequent inversion, found in the heterozygous state in 33% of females,
      helps to explain the discrepancies observed between the genetic and physical map
      distances in this region of the X chromosome. It also illustrates the biological
      insights which can be gleaned by sequencing the human genome.

PMID- 9140404
TI  - Global distribution of the CCR5 gene 32-basepair deletion.
AB  - A mutant allele of the beta-chemokine receptor gene CCR5 bearing a 32-basepair
      (bp) deletion (denoted delta ccr5) which prevents cell invasion by the primary
      transmitting strain of HIV-1 has recently been characterized. Homozygotes for the
      mutation are resistant to infection, even after repeated high-risk exposures, but
      this resistance appears not to be total, as isolated cases of HIV-positive
      deletion homozygotes are now emerging. The consequence of the heterozygous state
      is not clear, but it may delay the progression to AIDS in infected individuals. A
      gene frequency of approximately 10% was found for delta ccr5 in populations of
      European descent, but no mutant alleles were reported in indigenous non-European
      populations. As the total number of non-European samples surveyed was small in
      comparison with the Europeans the global distribution of this mutation is far
      from clear. We have devised a rapid PCR assay for delta ccr5 and used it to
      screen 3,342 individuals from a globally-distributed range of populations. We
      find that delta ccr5 is not confined to people of European descent but is found
      at frequencies of 2-5% throughout Europe, the Middle East and the Indian
      subcontinent (Fig. 1). Isolated occurrences are seen elsewhere throughout the
      world, but these most likely represent recent European gene flow into the
      indigenous populations. The inter-population differences in delta ccr5 frequency
      may influence the pattern of HIV transmission and so will need to be incorporated
      into future predictions of HIV levels.

PMID- 9140405
TI  - Academic-industry research relationships in genetics: a field apart.
AB  - Academic-industry research relationships (AIRRS) have become widely accepted and
      increasingly common in the life sciences. Using nationwide surveys from the
      United States, we found significant differences between the AIRRs of genetics
      firms and faculty and those of other firms and faculty. Significantly more
      genetics than non-genetics firms funded AIRRs, and genetics firms' AIRRs were
      larger and longer. Genetics faculty with AIRRs were significantly more likely
      than non-genetics faculty to report that patents, licenses, new companies and
      trade secrets had resulted from their university research; and that they had
      refused to share research results of biomaterials with colleagues.

PMID- 9140406
TI  - Yeast SAS silencing genes and human genes associated with AML and HIV-1 Tat
      interactions are homologous with acetyltransferases.

PMID- 9140407
TI  - Cancer research breaks out.

PMID- 9140408
TI  - New opportunities for uncovering the molecular basis of cancer.

PMID- 9140409
TI  - A breakpoint map of recurrent chromosomal rearrangements in human neoplasia.
AB  - Cytogenetic studies over the past few decades have revealed clonal chromosomal
      aberrations in almost 27,000 human neoplasms. Many of these neoplasia-associated
      chromosomal abnormalities have been characterised at the molecular level,
      revealing previously unknown genes that are closely associated with the
      tumorigenic process. Information on chromosome changes in neoplasia is growing
      rapidly, making it difficult to identify all recurrent chromosomal aberrations.
      We have developed a computer program to ascertain, for the first time, all
      recurrent structural abnormalities in all haematological malignancies and solid
      tumours published up to June 1996. Out of 26,523 cases, a total of 215 balanced
      and 1,588 unbalanced recurrent aberrations were identified among 75 different
      neoplastic disorders. Our compilation of all recurrent balanced and unbalanced
      neoplasia-associated rearrangements should help in directing future efforts aimed
      at identifying the molecular mechanisms involved in tumorigenesis.

PMID- 9140410
TI  - Preventing harm in resuscitation medicine.
AB  - Most often when we proceed to resuscitate the severely unwell and injured various
      factors conspire against a fully informed consent and therefore we gain
      permission to proceed on the basis of presumed or implied consent, and this
      consent is based on the belief that the resuscitation is likely to procure more
      benefit than harm. If the balance of benefit and harm is unfavourable then to
      proceed to resuscitate is inappropriate as consent cannot be presumed nor
      implied. The concept of benefit has been aired in the literature and many have
      argued the threshold where benefit becomes futility. However, the harm of
      resuscitation has had scant attention and I have discussed this using Jennett's
      headings of unnecessary, unsuccessful, unkind, unwise and unwanted. Both benefit
      and harm in resuscitation are difficult to quantify but even so an appreciation
      of their balance should guide the resuscitators, the family and the patient in
      their decision to proceed. Often, and appropriately, a decision to proceed will
      be made on the basis of a perceived marginal benefit over harm balance made more
      appealing by an alternative of certain death if resuscitation is not undertaken.
      This is appropriate if the perceived benefits and harms are made explicit and are
      appreciated by all concerned so that decisions are not made on the basis of ill
      informed expectations. However, the balance is dynamic with a clearer view of the
      likely benefits and harms emerging as the patient responds or doesn't respond to
      resuscitation endeavours. If the treatment does not procure the hoped for
      benefits then all concerned would be disappointed but should not be surprised and
      should be willing to minimise the ongoing harms of resuscitation by withdrawing
      treatment as the balance becomes unfavourable. Hershaw suggests; "if doctors can
      not stop treatment once started they will be afraid to start treatment on
      patients who have a limited chance of success but who might benefit". By
      employing medical substituted judgement the resuscitators should recognise when
      the balance of benefit and harm becomes unfavourable and at this point the
      resuscitators have a moral obligation to withdraw resuscitation as they can no
      longer presume the patient's consent. By appreciation of the benefits and harms
      of resuscitation and by the use of medical substituted judgement to view these
      from the patient's perspective and by a commitment to withhold or withdraw
      resuscitation when we can not presume the patient's consent, then we will
      minimise the harms in resuscitation medicine.

PMID- 9140411
TI  - Early experience of primary angioplasty at Waikato Hospital.
AB  - AIM: Acute angioplasty for myocardial infarction without prior thrombolytic
      therapy (primary angioplasty) has been advocated as the preferred treatment for
      high risk infarct patients, however data is primarily from highly experienced
      units. This report describes the first year's experience of primary angioplasty
      at Waikato Hospital which is a moderate sized institution performing 300 elective
      angioplasty procedures per year. METHODS: Patients presenting with an acute
      infarction who were deemed to be either at high risk or who had a
      contraindication to streptokinase received primary angioplasty. The program
      operated 24 hours a day, 7 days a week with all procedural and clinical outcomes
      being prospectively recorded on a database. RESULTS: Fifty one patients underwent
      primary angioplasty in the first year. Vessel patency was achieved in 86%, with
      TIMI III flow present in 82%. Time from emergency room arrival to reperfusion
      averaged 95 minutes and median hospital length of stay was 5 days. Five (10%)
      patients died while in hospital: those in cardiogenic shock on presentation had a
      mortality of 33%, and the remainder 5%. CONCLUSIONS: These results suggest that
      primary angioplasty is logistically feasible in a moderate sized New Zealand
      hospital with clinical results similar to those reported by the large
      interventional centers in Europe and the USA.

PMID- 9140412
TI  - Multidrug resistant tuberculosis in Auckland 1988-95.
AB  - AIMS: To review all cases of multidrug resistant tuberculosis (MDRTb) in Auckland
      between 1988-95; and to look for ways in which the diagnosis and management may
      be improved. METHODS: Cases of multidrug resistant tuberculosis were identified
      from Green Lane Hospital tuberculosis laboratory records. Clinical details were
      obtained from hospital case records, and radiographs were reviewed. RESULTS: Nine
      of the 838 (1.1%) confirmed cases of tuberculosis had multidrug resistant
      tuberculosis. Eight were foreign-born and four had previously been treated for
      tuberculosis. Three patients underwent thoracic surgery. Two patients died and
      one was not treated, No relapses have occurred. Potential to improve on the
      treatment given was evident in retrospect in three patients. CONCLUSIONS:
      Assessment of risk factors for multidrug resistant tuberculosis and early
      transfer of specimens to a tuberculosis reference laboratory are required to
      enable multidrug resistance to be identified early. Extensive disease, drug side
      effects and coexistent medical problems make MDRTb very difficult to cure.
      Directly observed therapy is recommended for multidrug resistant tuberculosis
      cases and is underutilised in Auckland.

PMID- 9140413
TI  - Needle stick injuries in country general practice.
AB  - AIMS: The aims of this study were to determine the frequency of needle stick
      injury (NSI) in general practice, to determine what measures were being taken to
      protect against needle stick injury, and to gather other information regarding
      work practices, risk perception, and knowledge of transmission. METHODS: A postal
      survey was undertaken of all general practitioners and one practice nurse per
      practice address in selected areas of New Zealand. RESULTS: The response rate was
      82%. An incidence rate of 22 needle stick injuries in 100 health care workers per
      6 month period was found. For general practitioners alone the incidence rate was
      25 in 100 per 6 month period and for practice nurses it was 17 in 100 per 6 month
      period. Recommended precautionary measures were not being followed by most
      individuals. CONCLUSIONS: Needle stick injury is a substantial problem in general
      practice and exposes general practitioners and practice nurses to a serious risk
      of infection from bloodborne transmissible agents. All patients should be
      considered to pose a potentially high risk of infection and recommended
      precautionary measures should be followed at all times.

PMID- 9140414
TI  - Haematological side effects of clozapine: patient characteristics.
AB  - AIM: To determine the prevalence of neutropenia and agranulocytosis in patients
      taking clozapine since its introduction into New Zealand in April 1988. METHOD:
      Data was collected by Sandoz Pharma (NZ) Ltd on blood counts from all patients
      prescribed clozapine as part of its worldwide monitoring programme for this drug.
      The data was analysed by one of the authors (AEC). Case histories to illustrate
      the principal ways in which falls in white cells present. RESULTS: A total of 693
      patients have been exposed to clozapine between April 1988 and June 1995. The
      cumulative agranulocytosis rate for the first 7 years of use was 1.15%. There
      were eight cases of agranulocytosis and no deaths. An additional 14 cases
      neutropenia were reported (2.02%). CONCLUSIONS: The agranulocytosis and
      neutropenia rates reported from New Zealand compare favourably with those from
      larger overseas studies though the exposed patient base is modest.

PMID- 9140415
TI  - Detecting young adults with alcohol use disorder in a general practice.
AB  - AIM: To report the detection of alcohol use disorder in 339 general practice
      patients age 18-29 years over a 5 year period. METHOD: Information on alcohol use
      was recorded in the patient notes during clinical or screening assessment.
      Screening was undertaken as part of a health check which included questions on
      consumption, concern about use and liver function tests in selected patients. The
      notes of all patients in this age group were reviewed after 5 years to determine
      the prevalence of alcohol use disorder and the method of detection. RESULTS:
      Information on alcohol use was recorded for 236 patients (70%), collected at a
      screening check for 202 patients and clinically for 34 patients. No information
      was recorded for 103 patients. Alcohol use was recorded for 83% of the women
      predominantly in association with other screening checks (cervical smears and
      antenatal checks). Alcohol use was recorded for 59% of the men, most of whom were
      screened on an opportunistic basis when attending for a consultation or linked to
      a clinical follow-up appointment. The criteria for alcohol use disorder was met
      by 16% of the men and 6% of the women whose alcohol use had been assessed either
      clinically or by screening. Overall, just under half of those identified with
      alcohol use disorder were detected by the screening programme. CONCLUSION: Both
      screening and clinical detection contributed to the identification of alcohol use
      disorder in this age group. Women were screened more successfully than men in
      association with other checks. A considerable proportion of men remained
      unscreened and a strategy for improving detection in this group is discussed.

PMID- 9140416
TI  - Gatekeepers no more: family practitioners as power brokers and fence wanderers.
AB  - The term gatekeeping in the context of primary care is neither controversial nor
      appropriate; it cannot be used to describe the complex interactions between
      general practitioners, their patients and the complexities of the evolving health
      system, euphemistically called health reform. Advocacy has now become paramount
      if general practice is to survive as a discipline in the face of competing
      economic forces eroding total patient care.

PMID- 9140417
TI  - Unauthorised disclosure of patient information.

PMID- 9140418
TI  - Is gallbladder sludge on transabdominal ultrasound an indication for
      cholecystectomy?

PMID- 9140419
TI  - Aids to smoking cessation.

PMID- 9140420
TI  - What is in a name?

PMID- 9140421
TI  - Fatty diet, mitochondria and Parkinson's disease.

PMID- 9140422
TI  - General practitioner obstetrics.

PMID- 9140423
TI  - Sunscreen dermatitis.

PMID- 9140424
TI  - Hodgkin's disease in a patient with Klippel-Trenaunay syndrome.

PMID- 9140425
TI  - A new stance in the doctor-patient relationship?

PMID- 9140426
TI  - To screen or not to screen.

PMID- 9140427
TI  - Effect of screening in the Nordic cancer control up to the year 2017.
AB  - The purpose of this study was to estimate the effect of screening for cancer on
      mortality, quality of life and cost in the Nordic countries up to 2017. Data from
      the Nordic Cancer Registries were used to predict, by means of the age-period
      cohort models, cancer mortality assuming no screening, the screening actually
      practised and most effective screening observed. Cost of screening was assessed
      assuming the cost of breast, cervical and colorectal cancer screening per person
      as well as treatment, follow-up and terminal care by stage. The results were
      adjusted for quality of life directly associated with screening and indirectly
      induced as dementia by the prolongation of life. Ultimately, in the year 2017
      screening will prevent about 4000 deaths in the Nordic countries, most (91%)
      cervical cancer and a smaller proportion of breast cancer (18%) and colorectal
      cancer (18%) deaths are preventable. This is equal to 5.7% among all potential
      cancer deaths in 2017, which corresponds to about one life year gained due to all
      cancer screening per 1000 years lived by the Nordic population in 2017.
      Adjustment for quality of life may at most reduce the benefit by about 20%. The
      cost of screening for breast cancer is expensive, that for cervical cancer is
      likely to be cost saving, and cost of screening for colorectal cancer may occupy
      an intermediate position. It is concluded that about 6% of the cancer deaths in
      the Nordic countries can be prevented by screening. This figure is fully
      realistic given the Nordic type of organized screening programmes, whereas many
      other predictions affecting cancer burden are more speculative.

PMID- 9140428
TI  - Specification of the dose to organs at risk in external beam radiotherapy.
AB  - Reporting of the clinical relevant dose to organs at risk (OR) and other normal
      tissues is crucial in trials and protocols where the aim is to assess late
      complications and to increase the therapeutic ratio for external beam
      radiotherapy. The dose distribution in normal tissues and ORs are, however, most
      often heterogeneous, at least when more than two opposing beams are applied. To
      decide the most clinical relevant dose with respect to late occurring
      complications is therefore not a straight forward problem. In this work we
      discuss what parameters characterise the dose-volume-histogram (DVH) best by
      calculating normal tissue complication probabilities (NTCPs) by using the Lyman
      model and various sets of statistical parameters drawn out from the DVHs. These
      NTCPs are compared to NTCPs calculated from the full DVHs, when the sets of
      parameters are evaluated. Our calculations indicate that the NTCP based on the
      Lyman model is best correlated to the Dmax value for serially organised tissues
      such as the spinal cord. For organs, described largely as tissues organised in
      parallel, the Dmedian or Dmean of the DVH may be applied. Our calculations reveal
      that Dmean is the parameter of choice when Dmedian is quite small, but when the
      two parameters approach each other. Dmedian will be a better choice, using a
      unity volume fraction. For ORs characterised by a mixed serial and parallel
      functional structure, as the heart, neither Dmax, Dmedian nor Dmean may predict
      the actual NTCP.

PMID- 9140430
TI  - Self-care responses to illness of patients with various cancer diagnoses.
AB  - The purpose of this study was to examine the relationship between self-care
      responses and variables concerning health status, disease and treatment,
      socioeconomic resources, demographic characteristics, and health beliefs in a
      heterogeneous sample of 227 cancer patients referred to home care. Data were
      collected prior to discharge from the hospital using the OARS Functional
      Assessment Questionnaire, the Karnofsky Performance Status, the Multidimensional
      Health Locus of Control Scale, and the Preference for Participation in Care Tool.
      The results indicated that the variables related to health status, disease and
      treatment were highly correlated with self-care behavior (SCB), and to a lower
      extent to self-care preference (SCP). Karnofsky performance status, cancer
      related impairments, perceived physical health, and stage of disease were
      identified as significant predictors of SCB explaining 57% of the variance. Age,
      gender, education, live-in resources, and perceived mental health were dominant
      predictors of SCP explaining only 17% of the variance. Further research endeavors
      should investigate other models that might prove to be better predictors of SCP.

PMID- 9140429
TI  - Hormone-metabolic status in moderately smoking breast cancer patients.
AB  - One hundred and eighteen primary breast cancer (BC) patients, 35 of whom were
      smokers, in clinical stages I-II of the disease were examined. In order to
      investigate whether smoking changes endocrine function in BC patients, some
      indices of the hormone-metabolic status of smoking and non-smoking patients of
      reproductive and menopausal age were compared. It was found that in smokers with
      BC there was a decline in body weight and body fat content, a lack of lean body
      mass accumulation along with body mass increase, a tendency to
      hypotriglyceridemia and hypoinsulinemia, accelerated development of the upper
      type of body fat distribution with ageing, intensified gonadotropin secretion,
      shifts in steroidogenesis and SHBG level and elevated catecholamine execretion.
      It is suggested that a possible relation between hormone-mediated effects
      inherent to smoking and the mechanisms promoting genotoxic type of hormonal
      carcinogenesis and the factors of breast cancer prognosis cannot be excluded.

PMID- 9140431
TI  - Palliative major amputation and quality of life in cancer patients.
AB  - Limb sparing surgery has replaced the amputation surgery in the treatment of limb
      sarcomas. Recurrent or persistent disease constitutes a major problem. Local
      symptoms such as agonizing pain, fractures, tumor fungation, inability to walk
      and inability to maintain daily activities, further impair the patient's quality
      of life. In this clinical set-up palliative amputation should be considered.
      Eighteen patients with soft-tissue or bone sarcomas and 3 patients with
      metastatic carcinoma underwent palliative major amputation. Hemipelvectomy was
      performed in 3 patients, hip disarticulation in 10, knee disarticulation or below
      knee amputation in 3 patients, shoulder disarticulation in one patient and
      forequarter amputation in 4 patients. Local control of the disease and pain and
      improvement of the performance status were observed in 19 evaluable patients. The
      mobility was restored in 15 patients with lower limb surgery. The median survival
      following the procedure was 9 months. There was only one case of immediate post
      operative death. Severe phantom pain was not reported by any of the patients.
      Quality of life was reported to be improved by two-thirds of the patients. To
      conclude, we have, found palliative major amputation surgery worth performing in
      low-performance status cancer patients with locally advanced disease.

PMID- 9140432
TI  - Serum lactate dehydrogenase level in patients with nasopharyngeal carcinoma.
AB  - Serum lactic dehydrogenase (LDH) levels of 465 patients with nasopharyngeal
      carcinoma (NPC) were assayed retrospectively. Four cohorts were selected in order
      to investigate the enzymes: 1) stage IV disease (118 cases) with pretreatment
      measurement, 2) relapse cases (159 cases) with pretreatment measurements, 3) no
      evidence of disease (217 cases) with spotting or serial measurements, and 4)
      monitoring of response to cytotoxic chemotherapy (34 cases). Higher serum LDH
      levels and more cases with elevated values were found in metastatic disease,
      especially relapse cases with liver and/or multiple organ site metastases. Serum
      LDH levels in locoregional disease were rarely found to be greater than two times
      the normal level. The value of serial serum LDH measurement for detecting disease
      relapse in the follow-up of patients with NPC is limited. Twelve percent of cases
      with no evidence of disease demonstrated elevation in serum levels. Serum LDH
      levels were found to correlate with the clinical responsiveness to systemic
      chemotherapy. Cases with normal serum LDH before treatment had a better chance of
      survival than those with elevated levels (median: 53 vs. 10 months, p = 0.008).

PMID- 9140433
TI  - Iridium-192 interstitial brachytherapy in carcinoma of the tongue. The importance
      of various tumor and physical parameters.
AB  - A detailed analysis of host-tumor factors and interstitial physical factors
      influencing the disease-free control in carcinoma of the tongue was carried out.
      Twenty-eight cases of carcinoma of the tongue T1-3, NO-1, MO were treated
      radically with combined external irradiation and 192Iridium interstitial
      brachytherapy (one patient received brachytherapy only). The teletherapy dose
      ranged from 44 Gy to 56 Gy (average 48 Gy), the brachytherapy dose ranged from 16
      Gy to 55 Gy (average 22 Gy). The interstitial practice involved loop technique in
      all the cases. Dose distribution analysis to assess factors influencing local
      control included indices of dose rate, source activity, inter-planar distance,
      and discontinuity in the prescribed isodose in other planes when compared to mid
      plane. Two-year actuarial disease-free survival (DFS) was 46% with primary
      treatment and 63% when salvage treatment was also included. DFS was significantly
      poorer when the interplanar distance at mid-plane exceeded 10 mm (p < 0.05).
      Similarly, tumor control was poorer (p < 0.008) when there was discontinuity in
      the prescribed isodose in 1 or 2 planes (1 cm superior and inferior to mid
      plane). Interplanar distance of around 10 mm, prescribed isodose continuity in
      all three planes and limiting the dose maximum within a factor of 2 will optimize
      the results of interstitial implants.

PMID- 9140434
TI  - Suramin in non-small cell lung cancer and advanced breast cancer. Two parallel
      phase II studies.
AB  - Suramin inhibits the growth of non-small cell lung cancer (NSCLC) and breast
      cancer in vitro by blocking the action of most known growth factors. The clinical
      efficacy of suramin was evaluated in patients with unresectable or relapsed NSCLC
      (n = 16) and advanced breast cancer (ABC) resistant to conventional therapies (n
      = 12). A plasma level > or = 200 micrograms/ml was maintained by three times
      weekly administrations using adaptive control with feedback. Treatment was
      continued until documented progression of disease or unacceptable toxicity. No
      clinical responses were observed in any patient. Median overall survival was 4.5
      months in NSCLC and 9 months in ABC patients. Mean treatment duration was 6.6
      weeks in NSCLC patients and 15.9 weeks in ABC patients. Treatment was
      discontinued due to disease progression in 14 patients, unacceptable adverse
      effects in 11 patients, while three patients refused to continue therapy. We
      cannot recommend this drug for further clinical trials in NSCLC and ABC.

PMID- 9140435
TI  - Transarterial infusion of cisplatin and doxorubicin in bladder cancer.
AB  - Forty-five patients (median age 63 years) with muscle invasive bladder cancer
      were treated with transcatheter intraarterial infusion (TAI) of cisplatin (CDDP)
      and doxorubicin. They received a total of 114 courses (median 3 courses per
      patient) of TAI. Complete response was obtained in 20 patients (44%), partial
      response in 17 (38%), stable disease in 6(13%), and progression of disease in 2
      patients (5%). The overall response rate was 82% at a median follow-up of 36
      months. The actuarial survival of the patient population was 72% at 5 years; 36
      patients were alive and 9 had died of cancer progression. The treatment was
      generally extremely well tolerated without major complications. The current study
      also revealed the fact that papillary carcinomas were more sensitive to this
      therapy than were non-papillary tumors. Overall, response rate and local control
      were significantly higher in low-grade than in high-grade tumors. The observed
      high complete response and good survival rate suggest that intraarterial CDDP and
      doxorubicin might be highly effective for localized invasive bladder cancer.

PMID- 9140436
TI  - The effect of tumor size on necrosis and polarographically measured pO2.
AB  - Tumor necrosis and oxygen status were investigated as a function of tumor size in
      three syngeneic murine carcinomas, MCa-4, OCa-I, and SCC-VII, in C3Hf/Kam mice.
      Tumor necrosis was estimated histologically, and tumor oxygenation determined by
      direct polarographic histography. As tumor volume increased necrosis increased
      significantly in all three tumor types (p < 0.001). Similarly, as tumor volume
      increased from 200 to 1400 mm3, hypoxia, defined as the percentage of measured
      pO2 values < or = 5.0 mm Hg, increased from 55.1% to 95.9%, 70.3% to 81.4%, and
      56.8% to 98.5% in MCa-4, OCa-I, and SCC-VII tumors respectively (p < 0.001).
      Correcting pO2 for necrosis reduced the tumor size dependence of measured tumor
      hypoxia in all three tumor types but in no case was the reduction significant.
      The main effect of correction was to shift the fitted curves of percent pO2
      values < or = 5.0 mm Hg down toward lower percentages for all tumors. This change
      was significant for MCa-4 and OCa-1 tumors (p < 0.001), but not for SCC-VII (p =
      0.054). Defining the influence of variables such as necrosis that affect
      polarographic assessment of tumor oxygenation is important to enhance the
      technique's reliability and prospect as an investigative and predictive tool.

PMID- 9140437
TI  - Rat salivary gland function after fractionated irradiation.
AB  - The aim of this study was to investigate longitudinal effects of fractionated
      irradiation, with various total doses, on salivary gland function in the rat.
      Female Sprague-Dawley rats were irradiated with 4, 5, 6, 7 or 8 Gy per day on
      five consecutive days. Irradiation was given to the head and neck region. Whole
      saliva was collected before and 2, 15 and 26 weeks after irradiation. In general
      the effects of irradiation on salivary gland function were found to be related to
      dose and time after exposure. Secretion rates were significantly decreased two
      weeks after irradiation with doses of 30 Gy or higher, after 15 weeks with 25 Gy
      or higher, and after 26 weeks with 20 Gy or higher. Response patterns to
      irradiation differed between the salivary constituents. Thus, the conclusions
      from this study are that early and late effects display different patterns and
      that the model used to study variations in salivary gland function after
      fractionated irradiation must be adjusted to the question addressed.

PMID- 9140438
TI  - Cell line specific radiosensitizing effect of zalcitabine (2',3'
      dideoxycytidine).
AB  - The potential of zalcitabine (ddC) to act as an ionizing radiation response
      modifier was tested on exponentially growing human cancer cells in vitro. Two
      human cell lines, WiDr (colon) and MCF-7 (breast) were exposed to ddC at 10
      microM concentration for various lengths of time (18, 24, 48 and 72 h). On the
      WiDr cell line the dual effect of concentration and duration of exposure prior to
      irradiation was investigated. Experimental endpoints were clonogenicity and
      viability, as measured by colony formation assay (CFA) and MTT assay
      respectively. The impact on cell-cycle distribution prior to irradiation was
      assessed by flow cytometry using a double labeling technique (propidium iodide
      and bromodeoxyuridine pulse label). A significant reduction in surviving fraction
      and viability was observed for WiDr-cells irradiated after pre-exposure to 10
      microM for 18, 48 and 72 h as compared to corresponding irradiated controls. At
      lower concentrations (1 and 5 microM), the radiosensitizing effect was only
      significant after a 72-h exposure (assessed by CFA). For MCF-7, ddC induced a
      significant modification of the dose response only with 24 and 48 h
      preincubation. However, the overall effect was less pronounced as compared to
      WiDr. Cell-cycle analysis showed accumulation in S-phase, 48 and 72 h after
      treatment with 10 microM ddC in the WiDr cells, with a progressive shift to late
      S-phase as shown by the biparametric analysis. The degree of radiosensitization
      is cell-line dependent with the most important sensitization observed on the most
      "radioresistant cell line", i.e., the cell line with the lowest alpha value and
      highest SF 2 (WiDr). For WiDr, radiosensitization by ddC depends on the duration
      of exposure and the concentration of the drug.

PMID- 9140439
TI  - Induction chemotherapy with versus without hormonal synchronisation in locally
      advanced breast cancer.
AB  - Sixty-nine patients with locally advanced breast cancer were given induction
      chemotherapy with doxorubicin and cyclophosphamide (day 1) followed by
      methotrexate and 5-Fu (day 8). Thirty-two of these patients were also given
      tamoxifen (days 2-6) in an attempt to induce a G1 arrest in cancer cells, and
      oestrogen (days 7-8) to stimulate proliferation and thus induce a synchronized
      wave of proliferating cells. The induction therapy response rate was 61% in the
      series as a whole (n = 69), but was found to be significantly better in the group
      on the tamoxifen/oestrogen synchronization regimen than in the remainder on
      chemotherapy alone (82% vs. 43%). This difference was particularly marked in the
      respective receptor-positive subgroups [90% (9/10) vs. 30% (3/10); p < 0.001].
      The findings suggest that, in combination with chemotherapy, tamoxifen/oestrogen
      therapy, given in the sequence outlined here, constitutes a promising regimen for
      the treatment of locally advanced receptor-positive breast cancer patients.

PMID- 9140440
TI  - Alkaline phosphatase of cancerous larynx tissue in comparison with the placental
      enzyme. Biochemical and histochemical studies.
AB  - Tissue specimens of squamous cell carcinoma of the larynx from twenty patients
      were processed for histological and histopathological characterization. A
      histochemical study of alkaline phosphatase (ALP) was carried out using the
      simultaneous azo coupling method, and biochemical studies were performed using
      disodium phenylphosphate as substrate. Full-term, normal placentae were used for
      comparison. The specific activity of ALP from cancerous laryngeal tissue was 8.9
      mKAU/mg protein compared with 154.7 mKAU/mg protein in the placenta. The ALP was
      localized histochemically in tumor cells (tumor-specific), blood vessels
      (vascular) and fibrous tissue (interstitial). The tumor-specific phosphatase was
      sensitive to inhibition by L-phenylalanine, L-leucine and to a lesser degree by L
      tryptophan and levamisole. Placental ALP, on the other hand, was completely
      inhibited by levamisole, more resistant to leucine and more sensitive to
      phenylalanine and tryptophan. Biochemical estimation of ALP in cancerous
      laryngeal tissue combined with inhibition studies revealed that the tumor
      specific activity of ALP constitutes 15% of the total ALP activity while the
      major isoenzyme was the vascular ALP, and around one-third of ALP activity was
      attributed to the interstitial enzyme. The characterization and localization of
      these isoenzymes are described and compared with that of the placenta. The
      significance and implications of the above findings are presented.

PMID- 9140441
TI  - Metastatic signet-ring cell adenocarcinoma to the urinary bladder.

PMID- 9140442
TI  - Adenocarcinoma of the fallopian tube. Natural history of an isolated splenic
      metastasis.

PMID- 9140443
TI  - Non-AIDS-related primary intraosseous Kaposi's sarcoma: case report and
      literature review.

PMID- 9140444
TI  - Reduction of brain metastasis following immunotherapy with interleukin-2 for
      stage IV renal cell cancer.

PMID- 9140445
TI  - Comparison of efficacies of ondansetron and dixyrazine for prophylaxis of emesis
      during induction treatment in acute myelogenous leukemia. A pilot study.

PMID- 9140447
TI  - Clinical significance of cytogenetic findings in solid tumors.
AB  - Chromosome analysis of solid tumors is becoming an increasingly useful tool to
      help establish a correct diagnosis and to provide prognostically important
      information. Characteristic karyotypic patterns in terms of degree of cytogenetic
      complexity and type of nonrandom abnormalities may help to distinguish neoplasia
      from a nonneoplastic lesion and to differentiate between a benign and a malignant
      tumor. More importantly, the presence of a specific or pathognomonic change may
      confirm or refute a suspected diagnosis, provide an alternative, unsuspected
      diagnosis, and trace the origin of a metastasis. Presently, specific cytogenetic
      abnormalities may be of substantial, and sometimes decisive, help in four groups
      of differential diagnostic dilemmas: (1) Benign vs. malignant epithelial tumors
      of the kidney, thyroid gland, salivary glands, and ovary; (2) Benign vs.
      malignant mesenchymal tumors of adipose and muscle tissue; (3) Differentiation
      between various malignant bone and soft tissue tumors: and (4) Diagnosis of
      undifferentiated small-cell round-cell tumors. In addition to the diagnostic
      value, karyotypic findings may provide prognostic information. Thus, the presence
      of an abnormal clone and/or complex rearrangements is a poor prognostic sign in,
      e.g., carcinomas of the ovary, prostate, bladder, colon, and pancreas.
      Furthermore, characteristic cytogenetic aberrations are now known to be valuable
      prognostic parameters in malignant melanoma, malignant fibrous histiocytoma, germ
      cell tumors, neuroblastoma, and squamous cell carcinoma of the head and neck
      region. Many of the correlation analyses are preliminary, but they all point in
      the same direction, namely that cytogenetic studies will soon play the same
      essential role in the management of patients with solid tumors as they do today
      in hematologic oncology.

PMID- 9140446
TI  - Ketorolac tromethamine in cancer pain.

PMID- 9140448
TI  - Impact of the in vitro technique used on the cytogenetic patterns in pleomorphic
      adenomas.
AB  - The cytogenetic observations in 97 new cases of pleomorphic adenomas are
      reported. They were all studied by in vitro technique using enzymatic
      pretreatment of the explanted material. The results, together with 26 previously
      reported cases studied by the same method (series II), were compared with a group
      of 130 adenomas (series I) investigated in cultures of only mechanically
      dispersed material. The results showed that in series II there was a substantial
      reduction of normal stemlines, an increase of cases with t(3;8)(p21;q12) and, in
      particular, of those with other 8q12 involvement. There was a similar frequency
      of cases with 12q13-15 aberrations in both series whereas, in series II, there
      was a moderate increase of the cases with "unique" abnormal stemlines. In
      comparison the German material, comprising 220 cases also studied by the
      enzymatic method, revealed a much higher frequency of cases with a normal
      stemline and a much lower frequency of adenomas with 8q12-involvement and of
      cases with unique stemlines. The results emphasize the need and importance of a
      meticulous documentation of all details of the in vitro technique used, for
      instance: explantation methods, composition of media, growth periods in vitro,
      and methods of harvest.

PMID- 9140449
TI  - Cytogenetic polyclonality in tumors of the breast.
AB  - Cytogenetically unrelated clones are found in half of all carcinomas of the
      breast and also in the epithelial fraction of many benign breast tumors. The
      chromosomal aberrations thus detected are clearly nonrandom and appear to be the
      same as those often seen in other tumors as sole karyotypic anomalies. Clonal
      chromosome abnormalities are not found in histologically normal breast tissue.
      Cytogenetically unrelated clones may be found in both primary tumors and
      secondary lesions, be it within the same breast (multifocal carcinomas), in the
      contralateral breast (bilateral carcinomas), or in lymph node or other
      metastases. The aberrations are present in topologically separate tumor domains
      and may confer on the cells that harbor them different types of cancer-specific
      behavior, such as the ability to metastasize and invade locally. Whereas the
      available evidence thus strongly indicates that the cells carrying clonal
      karyotypic aberrations all are part of the neoplastic parenchyma, it is less
      certain whether cytogenetic polyclonality actually signifies a multicellular
      tumor origin, although we think that this is the explanation that best
      accommodates the cytogenetic data. But even if it should eventually be shown that
      the seemingly unrelated clones have some submicroscopic tumorigenic mutation in
      common, the observed karyotypic heterogeneity is remarkable and goes far beyond
      what one has become accustomed to from most other tumor types. To understand how
      the various clones interact during mammary carcinogenesis will be a major task in
      future breast cancer research.

PMID- 9140451
TI  - Cytogenetics of carcinoma of the cervix uteri: a review.
AB  - Cytogenetic studies on carcinoma of the cervix have shown the nonrandom
      involvement in structural changes of a number of chromosomes, particularly
      chromosomes 1, 3, 5, 11, and 17. Apart from chromosome 5, where a short-arm
      isochromosome is the commonest derivative, these chromosomes most often undergo
      short-arm deletions. Notably, chromosome 17 may have undergone structural changes
      that result in loss of the tumor suppressor gene TP53 on 17p; chromosomal
      translocations may in some tumors perform the function that in others is provided
      by human papillomavirus protein complexing with and inactivating this gene. The
      chromosome 1 changes may sometimes result in the duplication of long-arm
      material. Although there have been few comparable studies on the preinvasive
      stages of cancer of the cervix, it is clear from earlier chromosome and
      quantitative DNA studies that, except perhaps in the "mild dysplasias," there
      already is clonal development that has resulted in an aneuploid population with a
      mode that, as in carcinomas, is either in the diploid or (in 50% or more)
      triploid-tetraploid range; spindle defects are prominent and may result in
      unequal segregation of the chromosomes into the daughter cells. Further
      characterization of the chromosomal changes in carcinoma of the cervix, and more
      particularly its preinvasive stages, using the new molecular DNA techniques is
      eagerly awaited.

PMID- 9140450
TI  - Advances in the analysis of chromosome alterations in human lung carcinomas.
AB  - A review of chromosomal analyses of human lung carcinomas is presented.
      Karyotypic studies have revealed multiple cytogenetic changes in most small cell
      lung carcinomas (SCLCs) and non-small cell lung carcinomas (NSCLCs). In SCLCs,
      losses from 3p, 5q, 13q, and 17p predominate; double minutes associated with
      amplification of members of the MYC oncogene family may be common late in
      disease. In NSCLCs, deletions of 3p, 9p, and 17p, +7, i(5)(p10), and i(8)(q10)
      often are reported. The recurrent deletions encompass sites of tumor suppressor
      genes commonly inactivated in lung carcinomas, such as CDKN2 (9p21), RB1 (13q14),
      and TP53 (17p13). Despite technical advances in cell culture, the rate of
      successful karyotypic analysis of lung carcinomas has remained low. Alternative
      molecular cytogenetic methods to assess chromosome changes in lung cancer,
      particularly comparative genomic hybridization (CGH) analysis, are discussed.
      Initial CGH studies confirm the existence of many of the karyotypic imbalances
      identified earlier in lung cancer and have revealed several recurrent
      abnormalities, such as 10q- in SCLC, that had not been recognized previously. The
      further application of such molecular cytogenetic approaches should enable
      investigators to define more precisely the spectrum and clinical implications of
      chromosome alterations in lung cancer.

PMID- 9140453
TI  - From chromosome aberrations to the high mobility group protein gene family:
      evidence for a common genetic denominator in benign solid tumor development.

PMID- 9140452
TI  - Genetics of retinoblastoma: a study.
AB  - We have analyzed 43 families with either familial retinoblastoma (RB) (four
      kindreds), bilateral sporadic RB (10 individuals), or unilateral sporadic RB (29
      individuals). Genetic studies focused on karyotype analysis, loss of
      heterozygosity of intragenic polymorphisms, and search for point mutations. We
      have been able to identify the genetic defect underlying the disease in eight
      cases. Deletions have been found in three patients with sporadic RB, two
      bilateral in one of which karyotyping had previously detected an interstitial
      deletion of chromosome 13 affecting (q13-q31) and one unilateral. Five different
      point mutations were responsible for three cases of bilateral sporadic RB, one
      case of bilateral sporadic RB, and one case of bilateral familial RB. The low
      frequency of constitutional mutations found in our study has led us to review and
      evaluate the possibilities and limitations of the present genetic analyses on RB
      and to access the different factors influencing the detection of mutations
      causing the disease, because genetic counseling is mainly based on mutation
      identification.

PMID- 9140454
TI  - Ten years of the cytogenetics of soft tissue tumors.
AB  - Recent cytogenetic and molecular genetic investigations in solid tumors in
      general, and in soft tissue tumors in particular, have provided us with a wealth
      of information. We have gained new insights in how tumors may arise, and some
      soft tissue tumors besides their identification by pathology now also have a
      genetic identity. This genetic identity is defined by: specific chromosome
      changes and by molecular changes related to the chromosome anomalies. However,
      much work remains to be done. In soft tissues as in other solid tumors many tumor
      types await the first or more extensive chromosome investigation, and in those in
      which nonrandom, especially simple chromosome changes emerge, molecular studies
      are to be undertaken starting from the breakpoints. Those tumors that seem to
      deviate chromosomally or molecularly from the expected, because of already
      established genetic changes, must be more thoroughly investigated by both
      pathologists and geneticists. The same accounts for the molecular investigation
      of chromosomally normal tumors known to show subtypes with specific chromosomal
      changes: e.g. lipoma, leiomyoma.

PMID- 9140455
TI  - Molecular cytogenetics of bone and soft tissue tumors.

PMID- 9140456
TI  - Cytogenetic findings in 73 osteosarcoma specimens and a review of the literature.
AB  - Tumor-specific chromosomal abnormalities have been identified in several
      histologic subtypes of sarcomas. Characterization of recurrent chromosomal
      abnormalities has provided direction for molecular investigations of
      pathogenetically important genes. Cytogenetic reports of osteosarcoma, the most
      common primary malignant bone tumor, are relatively rare. In this study, 73
      osteosarcoma specimens from 51 patients were cytogenetically analyzed following
      short-term culture. Clonal chromosomal abnormalities were detected in 47 and
      included one haploid specimen, 18 near-diploid specimens, 17 near-triploid, 8
      near-tetraploid, 1 near-hexaploid, and 2 specimens with multiple clones of
      different ploidy levels. Examination of the present data and previously published
      data (111 clonally abnormal osteosarcoma specimens) reveals that chromosomal
      bands or regions 1p11-13, 1q10-12, 1q21-22, 11p15, 12p13, 17p12-13, 19q13, and
      22q11-13 are most frequently rearranged and the most common numerical
      abnormalities are +1, -9, -10, -13, and -17. Partial or complete loss of the long
      arm of chromosome 6 also was seen in all cases of the present study and all
      previously published cases describing structural abnormalities of 6q. Parosteal
      osteosarcoma, a prognostically favorable osteosarcoma subtype, was characterized
      by the presence of a ring chromosome accompanied by no or few other
      abnormalities. Complex karyotypes were seen nearly exclusively in the high-grade
      lesions. These findings indicate that specific chromosomal bands and/or regions
      are nonrandomly involved in osteosarcoma and may provide useful clinical
      information.

PMID- 9140457
TI  - Cytogenetics of the progression of adult testicular germ cell tumors.

PMID- 9140458
TI  - Chromosomal constitution and developmental potential of human germ cell tumors
      and teratomas.

PMID- 9140459
TI  - Cytogenetic classification of renal cell cancer.
AB  - Cytogenetic and molecular genetic investigations in cancer are important tools to
      address problems of oncogenesis and tumor progression, of classification, and of
      diagnosis of tumors. A combination of advanced molecular genetic, cytogenetic,
      and (immuno) histopathologic analysis will contribute significantly to the
      elucidation of the oncogenic steps that lead to immortalization and subsequent
      malignant behavior. In this review written on the occasion of Dr. Avery
      Sandberg's 75th anniversary, we will present a model for the pathogenesis of
      renal cell tumors based on a new cytomorphologic classification and our
      (cyto)genetic analysis of about 175 renal cell tumors, together with the
      accumulated data in the literature.

PMID- 9140460
TI  - Cytogenetics of bladder cancer.

PMID- 9140461
TI  - Cytogenetic studies in prostate cancer: are we making progress?
AB  - Prostate cancer is the most commonly diagnosed male malignancy in western
      countries. Recent work in cell biology and molecular cytogenetics has led to a
      large amount of data on chromosomal abnormalities in prostatic tumors. A
      highlight of the literature describing both classical and molecular cytogenetic
      studies of prostate cancer is presented. By conventional cytogenetics,
      predominant changes included gain of chromosome 7, loss of Y, deletions of 7q and
      10q, and the appearance of double minutes. Using fluorescence in situ
      hybridization, predominant changes included gains of chromosomes 1, 7, 8, 8q
      sequences, 17, X and Y, and loss of chromosomes 1, 7, 8, 8p sequences, 10, 10q,
      16q and 17q sequences, 17 and Y. Newly defined sites by comparative genomic
      hybridization included loss of genetic material on 2q, 5q, 6q, 9q, 13q, 15q, 17p,
      and 18q, and gains at 1q, 2p, 3q, 7q, 9q, 11p, 16p, 20, 22, and X. These data
      indicate that multiple non-random genomic sites are involved in prostate
      tumorigenesis. This wide and relatively recent gain of information is likely to
      provide key clues to the biologic basis of this disease.

PMID- 9140462
TI  - FIFRA Subdivision F testing Guidelines: are these tests adequate to detect
      potential hormonal activity for crop protection chemicals? Federal Insecticide,
      Fungicide, and Rodenticide Act.
AB  - Recently, a major topic of discussion has been the impact of synthetic chemicals
      that possess the capacity to alter hormonal activity, the so-called "endocrine
      modulators," with potentially the capacity to alter the reproductive capability
      of humans. Particularly, various synthetic pesticides and industrial chemicals
      that persist in the environment and/or bioaccumulate have been implicated.
      Further, it has been alleged that the standard tests for pesticide registration
      as required by the U.S. Environmental Protection Agency (EPA) and other
      regulatory agencies may be inadequate to detect endocrine modulating effects. To
      address these shortcomings, it has been proposed that very specific tests for
      estrogen receptor binding, or in vitro cell response to chemicals, be used to
      identify potential endocrine modulators. However, such approaches have certain
      flaws that limit their application as screens. First, very specific tests, like
      receptor binding, evaluate only a single chemical event per test. Such tests do
      not measure toxicity or biological response. Isolated systems are very important
      for studying mechanisms of action or structure activity relationships, but can
      only provide a preliminary screen for a single mechanism of toxicity. Isolated
      systems can not be used to regulate a chemical without additional information.
      Second, they fail to test many other parts of the neuroendocrine control of the
      reproductive system. Testing for adverse effects in highly specific in vitro
      systems failed to replace whole-animal models in carcinogenesis and will also
      fail in reproductive toxicology because this system is too complicated for such
      as in vitro approach to be accurately predictive. Advanced tests, such as the EPA
      multigeneration study, are more effective, and reliable means for evaluation than
      any specific and narrowly focused screening tests. Experience has shown that a
      better approach to testing chemicals is to evaluate their effects on the whole
      animal. When one part of the system is adversely affected, various processes may
      be indirectly affected and can be detected in the animal model. For example, a
      modulation of testosterone synthesis could lead to (1) altered accessory sex
      organ morphology, size, and function; (2) decreased sperm counts; and (3) even
      decreased fertility. These and many other effects would be noted in toxicity
      studies that are already required for the registration of crop protection
      chemicals. The developmental and reproductive toxicity guidelines were recently
      reviewed in a hearing that included the representatives from the EPA, the public,
      and the Scientific Advisory Panel. The EPA kept the basic study design the same,
      but added a few new endpoints to further assess chemical-induced effects on
      reproductive development and function. The review presented herein concentrates
      on the required Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)
      testing for pesticides, and demonstrates how the massive arrays of sensitive
      endocrine endpoints that are delineated in FIFRA Subdivision F have been
      successfully used to detect both weak and potent hormonally modulating chemicals.
      For example, (1) diethyl-stilbestrol (DES), which is a potent synthetic
      therapeutic estrogen, (2) DDT, which is weakly estrogenic but persistent and
      bioaccumulating, and (3) dioxins, which have antiestrogenic properties, were all
      found as being hormonally active in tests similar or identical to FIFRA tests.
      All food-use pesticides have been evaluated using a comprehensive multigeneration
      reproduction test. Hence, the FIFRA testing procedures have been demonstrated to
      identify endocrine modulators of sufficient potency to represent a concern to
      human health.

PMID- 9140463
TI  - DNA-protein cross-links produced by various chemicals in cultured human lymphoma
      cells.
AB  - Chemicals such as cis-platinum, formaldehyde, chromate, copper, and certain
      arsenic compounds have been shown to produce DNA-protein cross-links in human in
      vitro cell systems at high doses, such as those in the cytotoxic range. Thus far
      there have only been a limited number of other chemicals evaluated for their
      ability to produce cross-links. The purpose of the work described here was to
      evaluate whether select industrial chemicals can form DNA-protein cross-links in
      human cells in vitro. We evaluated acetaldehyde, acrolein, diepoxybutane,
      paraformaldehyde, 2-furaldehyde, propionaldehyde, chloroacetaldehyde, sodium
      arsenite, and a deodorant tablet [Mega Blue; hazardous component listed as
      tris(hydroxymethyl)nitromethane]. Short- and long-term cytotoxicity was evaluated
      and used to select appropriate doses for in vitro testing. DNA-protein cross
      linking was evaluated at no fewer than three doses and two cell lysate washing
      temperatures (45 and 65 degrees C) in Epstein-Barr virus (EBV) human Burkitt's
      lymphoma cells. The two washing temperatures were used to assess the heat
      stability of the DNA-protein cross-link, 2-Furaldehyde, acetaldehyde, and
      propionaldehyde produced statistically significant increases in DNA-protein cross
      links at washing temperatures of 45 degrees C, but not 65 degrees C, and at or
      above concentrations of 5, 17.5, and 75 mM, respectively. Acrolein,
      diepoxybutane, paraformaldehyde, and Mega Blue produced statistically significant
      increases in DNA-protein cross-links washed at 45 and 65 degrees C at or above
      concentrations of 0.15 mM, 12.5 mM, 0.003%, and 0.1%, respectively. Sodium
      arsenite and chloroacetaldehyde did not produce significantly increased DNA
      protein cross-links at either temperature nor at any dose tested. Excluding
      paraformaldehyde and 2-furaldehyde treatments, significant increases in DNA
      protein cross-links were observed only at doses that resulted in complete cell
      death within 4 d following dosing. This work demonstrates that DNA-protein cross
      links can be formed in vitro following exposure to a variety of industrial
      compounds and that most cross-links are formed at cytotoxic concentrations.

PMID- 9140464
TI  - 3-Chloro-p-toluidine hydrochloride: in vitro mutagenicity studies for human
      health hazards determinations.
AB  - 3-Chloro-p-toluidine hydrochloride (CPT-HCl) is an aniline derivative used in the
      manufacture of the dye palatine fast yellow; it is also registered as a
      selective, low-volume-use (< 45 kg/yr) avicide. Three in vitro mutagenicity tests
      of CPT-HCl were performed according to methods recommended by the U.S.
      Environmental Protection Agency (EPA): the Ames/Salmonella assay, the Chinese
      hamster ovary/hypoxanthine-guanine phosphoribosyl-transferase (CHO/HPRT)
      mammalian cell forward gene mutation assay, and the CHO chromosome aberration
      assay. CPT-HCl did not display mutagenic activity using the Ames/Salmonella or
      CHO/HPRT assays. However, CPT-HCl induced statistically significant,
      concentration-dependent, metabolically activated increases in the proportion of
      aberrant cells and aberrations/cell in cultured CHO cells. Results are suggestive
      of minimal mutagenicity effects associated with exposure to anilines and their
      derivatives.

PMID- 9140465
TI  - Reactive oxygen species do not cause arsine-induced hemoglobin damage.
AB  - Previous work suggested that arsine- (AsH3-) induced hemoglobin (HbO2) damage may
      lead to hemolysis (Hatlelid et al., 1996). The purpose of the work presented here
      was to determine whether reactive oxygen species are formed by AsH3 in solution,
      in hemoglobin solutions, or in intact red blood cells, and, if so, to determine
      whether these species are responsible for the observed hemoglobin damage.
      Hydrogen peroxide (H2O2) was detected in aqueous solutions containing AsH3 and
      HbO2 or AsH3 alone but not in intact red blood cells or lysates. Additionally,
      high-activity catalase (19,200 U/ml) or glutathione peroxidase (68 U/ml) added to
      solutions of HbO2 and AsH3 had only a minor protective effect against AsH3
      induced damage. Further, the differences between the visible spectra of AsH3
      treated HbO2 and H2O2-treated HbO2 indicate that two different degradative
      processes occur. The presence of superoxide anion (O2-) was measured by O2(-)
      dependent reduction of nitro blue tetrazolium (NBT). The results were negative
      for O2-. Exogenous superoxide dismutase (100 micrograms/ml) did not affect AsH3
      induced HbO2 spectral changes, nor did the hydroxyl radical scavengers, mannitol,
      and DMSO (20 mM each). The general antioxidants ascorbate (< or = 10 mM) and
      glutathione (< or = 1 mM) also had no effect. These results indicate that the
      superoxide anion and the hydroxyl radical (OH) are not involved in the mechanism
      of AsH3-induced HbO2 damage. The results also indicate that although AsH3
      contributes to H2O2 production in vitro, cellular defenses are adequate to
      detoxify the amount formed. An alternative mechanism by which an arsenic species
      is the hemolytic agent is proposed.

PMID- 9140466
TI  - Upper respiratory tract surface areas and volumes of laboratory animals and
      humans: considerations for dosimetry models.
AB  - To facilitate the development of regional respiratory tract dosimetry comparisons
      between laboratory animal species and humans, published surface area (SA) and
      volume (VOL) data for the upper respiratory tract (URT) were reviewed. The review
      of the literature revealed that (1) different studies used different techniques
      to prepare specimens and make measurements, (2) different areas of the URT were
      measured, and (3) URT surface areas and volumes have been reported for a limited
      number of individual subjects within a species but for a relatively wide range of
      species. The published data are summarized in tables in this article. New
      measurements made in an F344 rat and in a female human subject are also
      presented. Despite the differences in experimental protocols, it was possible to
      fit allometric scaling equations to the data: In(SA, cm2) = -0.34 + 0.52 In(body
      weight, g) and In(VOL, cm3) = 1.70 + 0.78 In(body weight, g). Separate scaling
      equations were also fitted for rats alone. To illustrate the use of these scaling
      equations in quantitative human health risk assessment, two dose metrics
      (fractional absorption/cm2 URT SA and fractional absorption/g body weight) for
      predicted URT uptake in laboratory animals and humans were calculated for
      acrolein and epichlorohydrin. Expressed as an animal-to-human ratio, the 95%
      confidence interval for URT SA could change the predicted dose ratio by up to a
      factor of 2. Additional studies are needed to describe the entire URT (from the
      nares through the larynx) quantitatively and to decrease variability in scaling
      equation predictions as well as to develop additional species-specific scaling
      equations. Three-dimensional imaging techniques provide a noninvasive method to
      obtain URT surface areas and volumes in humans and the larger laboratory animals.
      Comparisons of magnetic resonance image (MRI) and computed tomography (CT) scans
      made as part of this study suggest that the greater clarity of the mucosal-air
      interface in the CT image provides better resolution for the study of anatomic
      features. Because there is no radiation exposure associated with MRI imaging,
      however, it is more safely used than CT scans in making repeated measurements in
      a subject to elucidate changes in URT geometry associated with normal nasal
      cycling or other physiological changes.

PMID- 9140467
TI  - Effect of beryllium chloride on porphyrin metabolism in pregnant mice
      administered by subcutaneous injection.
AB  - The effect of beryllium (Be) compounds on porphyrins was investigated in pregnant
      mice. The blood protoporphyrin (Proto) and zinc protoporphyrin (Zn Proto)
      concentrations were increased in pregnancy. Regardless of pregnancy or
      nonpregnancy, the Proto concentration was decreased after Be injection. Delta
      aminolevulinic acid dehydratase (ALA-D) and porphobilinogen deaminase (PBG-D)
      activities in blood were significantly elevated in the pregnant untreated (Con
      pregnant) group, compared to the nonpregnant mice untreated (Con-nonpregnant) and
      nonpregnant mice treated with Be (Be-nonpregnant) groups. The blood ALA-D
      activity of the pregnant mice treated with Be (Be-pregnant group) tended to
      decrease, compared to Con-pregnant group. The blood PBG-D activity in the Be
      pregnant group was significantly lower compared with that of the Con-pregnant
      group. The ALA-D and PBG-D activities in the spleen were also significantly
      elevated in the Con-pregnant group, compared to nonpregnant groups. However, it
      was noted that these values in the Be-pregnant group were almost the same as that
      of the Con-nonpregnant group and were significantly lower than that in the Con
      pregnant group. The elevation of ALA-D and PBG-D activities in the blood and
      spleen, which play a role in the hematopoietic function of mice, was observed in
      the Con-pregnant mice compared to the nonpregnant mice. However, the phenomenon
      was not observed in the Be-pregnant mice, it suggesting that Be suppressed the
      pregnancy-induced increase in hematopoietic function.

PMID- 9140468
TI  - Enhancing effects of phenobarbital and 3-methylcholanthrene on GST-P-positive
      liver cell foci development in a new medium-term rat liver bioassay using D
      galactosamine.
AB  - The carcinogenic potential of phenobarbital (PB) and 3-methylcholanthrene (3-MC)
      was assayed in a new medium-term carcinogenicity bioassay using D-galactosamine
      (DGA) as a nonsurgical method to induce liver cell regeneration in place of
      partial hepatectomy (PH). Rats were initially given a single ip injection (200
      mg/kg) of diethylnitrosamine (DEN) and after 2 wk on basal diet received 2 ip
      injections of DGA (300 mg/kg) at the end of wk 2 and 5. They were treated with
      one of the test compounds PB or 3-MC in the diet or fed basal diet for wk 3-8
      Carcinogenic potential was assessed by comparing the numbers and areas per square
      centimeter of glutathione S-transferase placental form-positive (GST-P+) foci in
      the livers of test chemical-treated animals with those of the control animals
      given DEN/DGA alone. Positive estimations of carcinogenicity were obtained for
      PB, which is a nongenotoxic liver tumor promoter, and for 3-MC, which is a
      genotoxic nonliver carcinogen. Increases of liver/body weight ratios and serum
      total cholesterol were observed in rats treated with PB or 3-MC. Interestingly,
      interlobe differences were found on the development of GST-P+ liver cell foci.
      Our results thus confirm that the present bioassay protocol with repeated
      administration of DGA instead of PH may offer a new and sensitive method to
      screen large-numbers of environmental liver and nonliver carcinogens.

PMID- 9140469
TI  - The redox status of malaria-infected erythrocytes: an overview with an emphasis
      on unresolved problems.
AB  - The various mechanisms involved in the redox defence of normal erythrocytes are
      adequately known. They are herein briefly reviewed, outlining the principal
      enzymes and metabolic pathways, such as superoxide dismutase, catalase,
      glutathione peroxidase and reductase, the hexose monophosphate shunt (HMS) and
      glutathione synthesis and turnover. The intraerythrocytic malaria parasite is
      imposing an oxidative stress on its host cell. Malaria infected cells produce O2
      , H2O2, enhance lipide peroxidation and activate host cell HMS. This stress is
      produced during the digestion of host cell hemoglobin by the parasite. Hence,
      both parasite and host cell must be able to confront this stress. The antioxidant
      defence systems of the parasite and the response of those systems in the infected
      host cell are reviewed, underscoring unresolved problems. Nothing is virtually
      known on the parasite's glutathione metabolism, and on possible interactions
      between host cell and parasite antioxidant defence systems. The postulate that 1.
      host cell activated HMS in conjunction with purine salvage can provide purine
      nucleotides to the parasite, and 2. that glutathione transferase can participate
      in parasite resistance to antimalarial drugs, are also discussed.

PMID- 9140470
TI  - The European badger (Carnivora:Mustelidae) as intermediate host of further three
      Sarcocystis species (Sporozoa).
AB  - Three species of sarcocysts are described by light and electron microscopy from
      the European badger (Meles meles): Sarcocystis hofmanni n. sp. (a species
      otherwise occurring in roe deer, Capreolus capreolus), S. sp., cf. sebeki (c
      species usually parasitizing certain murids); and S. melis n. sp. (c species
      presumably specific for the badger).

PMID- 9140471
TI  - Rodent malaria parasites: molecular karyotypes characterize species, subspecies
      and lines.
AB  - The molecular karyotypes of the African murine malaria parasites P. berghei (3
      strains, 2 lines) P. yoeli (2 strains) P. chabaudi (3 strains, 1 line) and P.
      vinckei (4 strains) have been studied using orthogonal field alternation gel
      electrophoresis (OFAGE). The genome of each species was resolved into 9 to 11
      distinct chromosomal DNA banas molecules of varying intensities which seem to
      represent 14 chromosomes ranging in size from 600 kb to 3500 kb. The position of
      certain chromosomes allowed the identification of a unique karyotype for each of
      the strains and lines under study. P. yoelii appears by criteria of chromosome
      size, chromosome numbers and localisation of DNA probes to differ considerably
      from the other three rodent malaria species. The chromosomal location of 5 DNA
      probes allowed the identification of corresponding chromosomes in rodent malaria
      parasites and the differentiation between species and strains. Assignment of the
      "PMMSA" gene of P. c. chabaudi IP-PC 1 enables the distinction of the four rodent
      malaria species. The molecular karyotype combined to chromosomal assignment of
      DNA probes provides a useful tool for a more precise characterization by a
      genetic definition of malaria parasites.

PMID- 9140473
TI  - Between goat-farm biological variability of the nematode Muellerius capillaris
      first-stage larvea. Influence of anthelmintic treatment.
AB  - Seven dairy-goat farms from the centerwest of france were investigated for
      morphology and ecology of first-stage larvae (L1) of Muellerius capillaris before
      and after treatment of goats with febantel, a probenzimidazole anthelmintic. The
      lengths, survivals at 20 and -20 degrees C, and infectivity of L1 to intermediate
      host Helix aspersa, were different between farms. The between farms differences
      in survivals were reduced after treatment of goats with febantel. The observed
      between farm differences in L1 did not seem to be related to farm characteristics
      (intensity of treatments, susceptibility to febantel, and intermediate host
      species).

PMID- 9140472
TI  - Activity of albendazole-ivermectin combination and other filaricidal drugs
      against infective larvae, preadult, microfilariae and adult worms of Molinema
      dessetae in the rodent Proechimys oris.
AB  - The efficacy of albendazole-ivermectin combination was tested an adult and
      developing stages of Molinema dessetae in the rodent Proechimys oris. Albendazole
      and ivermectin, both given alone, suramin and diethylcarbamazine were used as
      reference compounds. The drug combination (albendazole at 10 mg/kg/ day x 5 days
      and Ivermectin at 0.04 mg/kg/day x 5 days) was effective against infective larvae
      and preadult worms, and substantially reduced the number of live adult worms. The
      known filaricidal agents, diethylcarbamazine (400 mg/kg twice daily x 5 days),
      ivermectin (0.2 mg/kg/day x 5 days), and suramin (40 mg/kg/day x 5 days), as well
      as albendazole (50 mg/kg/day x 5 days) were active on infective larvae, preadult
      worms, microfilariae and adult worms. All drugs had the same level of efficacity
      on infective larvae. Albendazole had the highest efficacy against adult and
      preadult worms and diethylcarbamazine was the most active on microfilariae.
      Although the drug combination was not as effective against preadult and adult
      worms as albendazole alone, the results indicate that albendazole-ivermectin
      combination at a low dose had prophylactic effect and suggest a possible
      macrofilaricidal activity.

PMID- 9140474
TI  - Is leishmaniasis endemic on the island of Minorca (Spain)? A human visceral case
      after living 13 years in Minorca.
AB  - Ecoepidemiological studies performed in Minorca (Balearic Islands) seem to show
      that leishmaniasis is not endemic in this island, even in the presence of the
      vector. All cases of leishmaniasis in man or dog diagnosed in the island seem to
      come from other Spanish regions. A recent case of human visceral leishmaniasis in
      a man who had not left Minorca for 13 years calls into question this assumption
      or the time that Leishmania may persist asymptomatic in the host.

PMID- 9140476
TI  - Pathogenicity of Cyclospora sp.

PMID- 9140475
TI  - The chemical and biological control of Lymnaea truncatula in natural watercress
      beds in the Limousin region (France).
AB  - The snails present in 17 natural watercress beds have been treated during 1 or 2
      years by a control associating the use of a molluscicide (CuCl2) and the
      introduction of a predatory snail, Zonitoides nitidus. Lymnea truncatula was
      eliminated in only one year of treatment in 14 stations, and in two years in the
      three others. Elimination of other aquatic pulmonate snails was effected in two
      years for L. glabra, in 3 years for L. palustris, and in only one year for Physa
      acuta. Z. nitidus has disappeared from 12 watercress beds during the 4th year
      after treatment; in the five others, the numbers of this predator increased
      during 1 or 2 years and then decreased before their disappearance.

PMID- 9140477
TI  - Recent news on trichinellosis: another outbreak due to horsemeat consumption in
      France in 1993.
AB  - A new outbreak of trichinellosis occurred in France in December 1993 and involved
      around 550 patients. The authors report here how recent knowledge on Trichinella
      have been helpful to investigate this outbreak.

PMID- 9140478
TI  - Latency of Plasmodium merozoites and drug-resistance. A review.
AB  - The authors summarize the results of recent work evidencing the existence of
      latent merozoites during the course of the erythrocytic cycle of the rodent
      Plasmodia. These merozoites, unlike the majority of merozoites released at
      schizogony, do not penetrate immediately into the erythrocytes and remain latent
      for a variable length of time. The merozoites of each of the species or
      subspecies show marked peculiarities which are responsible for the
      characteristics of their cycle. The presence of latent merozoites free in the
      blood, the asynchronous development, and the resistance to chloroquine, are three
      closely related factors. Knowing that the merozoite is so far drug resistant, and
      that latent merozoites can maintain the infection for any length of time, it
      appears important to take into account these purely biological data, when
      studying the drug resistance of the human falciparum malaria.

PMID- 9140479
TI  - Geographic distribution of Gongylonema pulchrum and Gongylonema macrogubernaculum
      from Macaca fuscata in Japan.
AB  - After a first report on the gullet nematode, Gongylonema pulchrum Molin, 1857,
      being found in the Japanese macaque, Macaca fuscata, in Kyushu, Japan, the
      geographic distribution of the parasite, a causative agent of gongylonemiasis in
      cattle and man, was examined in 181 monkeys transferred to the Japan. Monkey
      Centre from 23 sites in Japan, including Yaku-shima (Island). Yaku-shima is
      included in the World Natural Heritage List of the United Nations for its
      subtropical forests, which have an unusual variety of plant and animal species.
      G. pulchrum was found in M. fuscata yakui monkeys inhabiting Yaku-shima and M.
      fuscata fuscata monkeys inhabiting Honshu and an is and near Honshu. G.
      macrogubernaculum was found in M. fuscata yakui monkeys. Comparison of the two
      kinds of parasite specimens obtained from the variety M. fuscata yakui confirmed
      that G. macrogubernaculum Lubimov, 1931 is a valid species. Thus, the finding of
      G. macrogubernaculum constitutes a record of a newly identified host. M. fuscata
      yakui, and shows that Yaku-shima, Japan, is a natural locality of G.
      macrogubernaculum.

PMID- 9140480
TI  - Sandflies in the Greater Athens region, Greece.
AB  - During the period from May to October 1992, a survey of phlebotomine sandflies
      was conducted in the Greater Athens region where cases of human and canine
      leishmaniasis occur. Using castor-oil paper traps, a total of 3015 sandflies were
      caught. Of the identified specimens, 1002 (34.1%) were Phlebotomus neglectus, 541
      (18.4%) were P. papatasi, 182 (6.2%) were P. tobbi, 50 (1.7%) were P. simici, 30
      (1.0%) were P. alexandri, 3(0.4%) were P. sergenti and 1122 (38.2%) were
      Sergentomyia minuta. The seasonal activity of most Phlebotomus species was
      bimodal, while that of S. minuta was unimodal. The population density of
      sandflies varied significantly in different localities; it was low in most of the
      stations and high in some stations in the outskirts. Among the potential vectors
      of Leishmania spp., P. neglectus and P. Papatasi were the most widespread
      species. The former species showed high density in 12 of the 70 sampled stations,
      while the latter in only 4. Hence, the risk of transmission of sandfly-borne
      diseases is still present in the Greater Athens region.

PMID- 9140481
TI  - Molecular phylogenetic studies on filarial parasites based on 5S ribosomal spacer
      sequences.
AB  - This paper is the first large-scale molecular phylogenetic study on filarial
      parasites (family Onchocercidae) which includes 16 species of 6 genera: Brugia
      beaveri Ash et Little, 1962, B. buckleyi Dissanaike et Paramananthan, 1961; B.
      malayi (Brug, 1927) Buckley, 1960; B. pahangi (Buckley et Edeson, 1956) Buckley,
      1960; B. patei (Buckley, Nelson et Heisch, 1958) Buckley, 1960; B. timori Partono
      et al, 1977; Wuchereria bancrofti (Cobbold, 1877) Seurat, 1921: W. kalimantani
      Palmieri. Purnomo, Dennis and Marwoto, 1980: Mansonella perstans (Manson, 1891)
      Eberhard et Orihel, 1984; loa loc, Stiles, 1905; Onchocerca volvulus (Leuckart,
      1983) Railliet er Henry, 1910; O. ochengi Bwangamoi, 1969; O. gutturosa Neumann,
      1910; Dirofilaria immitis (Leidy, 1856) Railliet e Henry, 1911; Acanthocheilonema
      viteae (Krepkogorskaya, 1933) Bain, Baker et Chabaud, 1982 and Litomosoides
      sigmodontis Chandler, 1931. 5S rRNA gene spacer region sequence data were
      collected by PCR, cloning and dideoxy sequencing. The 5S rRNA gene spacer region
      sequences were aligned and analyzed by maximum parsimony algorithms, distance
      methods and maximum likelihood methods to construct phylogenetic trees. Bootstrap
      analysis was used to test the robustness of the different phylogenetic
      reconstructions. The data indicated that 5S spacer region sequences are highly
      conserved within species yet differ significantly between species. Spliced leader
      sequences were observed in all of the 5S rDNA spacers with no sequence variation,
      although flanking region sequence and length heterogeneity was observed even
      within species. All of the various tree-building methods gave very similar
      results. This study identified four clades which are strongly supported by
      bootstrap analysis the Brugia clade; the Wuchereria clade; the Brugia-Wuchereria
      clade and the Onchocerca clade. The analyses indicated that L. sigmodontis and A.
      viteae may be the most primitive among the 16 species studied. The data did not
      show any close relationship between Loa loa and D. immitis presently classified
      in the same subfamily, and the constitution of the Dirofilariinae subfamily is
      questionable.

PMID- 9140482
TI  - Description of cysticercoid of Coronacanthus vassilevi Genov, 1980
      (Cestoda:Hymenolepididae).
AB  - Genus Coronacanthus Spassky, 1954 contains three species--C. integra (Hamann,
      1891), C. omissa (Baer et Joyeux 1943) and C. vassilevi Genov, 1980--but larval
      stages of only first two species were described before. During 1991-1993
      cysticercoids of all three species were found from gammarid crustaceans in
      Eastern Carpathians. The article contains an illustrated description of the
      cysticercoid of C. vassilevi. It differs considerably from the formerly known
      Coronacanthus larvae by the egg-shaped (not lens-shaped) form of the cyst,
      absence of marginal thickening of the cyst wall, by the shape and length of
      cercomer and besides, by the invagination of the anterior part of the scolex.
      Microvilli on the cyst surface were not detected with light microscope. Cercomer
      of C. vassilevi is narrow and very long as for mammalian hymenolepidid (4.7 to 8
      times longer than cyst). The number (37-38), length (8-9 microns) and shape of
      rostellar hooks well correspond to those of adult worms (Genov, 1980).

PMID- 9140483
TI  - Evidence of alae in Aelurostrongylus abstrusus larvae examined by scanning
      electron microscope (SEM).
AB  - Aelurostrongylus abstrusus larvae lateral alae, previously noticed in cat lung
      sections, are described by SEM in larvae found in the faeces of an infected cat.

PMID- 9140484
TI  - Some preliminary data on the nature/structure of the PC-glycan of the major
      excretory-secretory product of Acanthocheilonema viteae (ES-62).
AB  - The structure of the PC-glycan of the major excretory-secretory product (ES-62)
      of Acanthocheilonema viteae has been investigated using endoglycosidases and
      lectins. Results obtained raise the possibility that it may be of the high
      mannose type. This, and the insensitivity of the PC-glycan to treatments which
      remove PC or choline from bacterial PC-glycans, suggests that it may be more
      analogous to fungal, than to bacterial PC-containing glycans.

PMID- 9140486
TI  - Falciparum malaria in naturally infected human patients: X. Ultrastructural
      pathological alterations of renal glomeruli.
AB  - The ultrastructural pathological alteration of the renal glomeruli is described
      in nine patients with acute Plasmodium falciparum infection. Glomeruli were large
      and hypercellular with various types of blood cells in their capillary lumena.
      These were occasionally occluded with enlarged endothelial cells. Epithelial
      cells, or podocytes, were hypertrophied with extensively diffused foot processes
      fusion and numerous villous transformation, or appeared cedemalous filling the
      urinary space. The glomeruli basement membrane was irregular in thickness or
      focally missing. Mesangial cells were undergoing proliferation and contained
      electron-dense deposits. Subendothelial, "hump"-like deposits, similar to those
      previously described in immune complex nephritis, were detected in most cases;
      but the largest amount was found in the three youngest patients in whom
      parasitaemia levels were the highest. This study showed that the kidney may
      become the target damage mediated by immunopathologic mechanism, and the
      developed lesions may correspond, for certain extent, to membranoproliferative
      glomerulonephritis with abnormal deposits, during the acute infection with
      falciparum malaria. The amount and density of the immune complex deposit could be
      correlated with the degree of parasitaemia and, in return with the degree of
      glomerular immunopathological alterations.

PMID- 9140485
TI  - Progress toward the development of vaccines against parasitic diseases: a review
      based on studies performed by participants of the Laveran seminar.
AB  - Although significant advances have been mode during the past 20 years, a better
      understanding of the orchestration of the immune response against a parasite
      candidate vaccine is still required for preparing vaccines which can induce the
      acquisition and the persistence of sterile immunity, without producing side
      effects in humans. This was, among others, one conclusion of the discussions
      between Thesis students and scientists. Only some aspects of the different steps
      of immune responses (recognition, protective effector mechanisms, cell
      regulation, cytokine activities, immunopathology, parasite escape mechanisms) are
      here reviewed. They are mainly related to malano and schistosomiasis, but also to
      other parasitic diseases, for which several experimental models have been
      developed.

PMID- 9140487
TI  - Interaction of artemisinin and tetracycline or erythromycin against Plasmodium
      falciparum in vitro.
AB  - Antimalarial activities of tetracycline (TC) and erythromycin (EM), alone or in
      combination with artemisinin (Qinghaosu, QHS), were studied using chloroquine
      (CQ)-sensitive (D6) and -resistant (W2) strains of Plasmodium falciparum in
      vitro. The antimalarial potency of TC (IC50 = 9862 nM for the CQ-sensitive
      parasite, 32414 nM for the CQ-resistant one) or EM (IC50 = 45787 nM for the CQ
      sensitive parasite, 33397 nM for the CQ-resistant one) was much less than that of
      QHS (IC50 ranging from 25 to 40 nM). The CQ-resistant falciparum parasite
      displayed a cross-resistance to TC, while both the drug-sensitive and -resistant
      parasites exhibited similar responses to EM. However, antimalarial potency of EM
      appeared to be less than that of TC against the drug-sensitive parasite. When TC
      was combined with QHS, an additive interaction was observed against the CQ
      sensitive falciparum parasite, while synergism was found with the CQ-resistant
      parasite. When EM was tested in combination with QHS, a potentiating interaction
      occurred with both the CQ-sensitive and resistant falciparum parasite. The above
      results indicated that the QHS combination with either TC or EM may be a
      promising antimalarial preparation with low recrudescence compared to artemisinin
      used alone in clinical practice.

PMID- 9140488
TI  - The pharmacokinetics of chloroquine in healthy and Plasmodium chabaudi-infected
      mice: implications for chronotherapy.
AB  - The schizogony of malarial parasite is a typical cyclic phenomenon where the
      different stages of parasite development appear at regular time intervals. Each
      of the stages is specifically sensitive to different antimalarial drugs.
      Knowledge of the details of the cycle, drug susceptibility and the
      pharmacokinetics of drugs, could allow the improvement of drug action by the
      chronotherapeutic approach: treatment at the time of appearance of the drug
      sensitive stage with a drug that displays rapid pharmacokinetics. Since murine
      malarias serve as preferable models for in vivo drug testing, the
      pharmacokinetics of subcutaneously (sc) administered chloroquine (CQ) were tested
      in the whole blood of healthy mice and in animals slightly (1.5-3.5% parasitemia)
      or heavily infected (21-25% parasitemia) with Plasmodium chabaudi chabaudi. The
      half-time of absorption was around 5 min and almost independent of parasitemia.
      The apparent half-time of drug concentration decay was around 40 min in healthy
      animals, about 90 min at low parasitemia and about 410 min in heavy infection,
      indicating that the concentration of CQ is a typical spike, that is prolonged by
      asymptomatic disease, and considerably more by the active accumulation of CQ in
      infected cells. The latter is confirmed by the 3-fold higher peak blood [CQ] at
      the trophozoite stage and < 1.5-fold increase during schizogony. In conjunction
      with our previous experiments which showed that a single sc injection of 5 mg/kg
      CQ is sufficient to eliminate the drug susceptible mid-term trophozoite stage,
      the present results seem to justify to propose the chronotherapeutic approach for
      the treatment of malaria.

PMID- 9140489
TI  - Plasmodium yoelii nigeriensis: biological mechanisms of resistance to
      chloroquine.
AB  - The sensitivity to chloroquine according to the degree of synchronicity of
      Plasmodium yoelii nigeriensis, which is considered to be the most resistant of
      the rodent malaria strains, was studied. The infection was synchronised by means
      of a Percoll-glucose gradient which separates rings and young trophozoites from
      other stages. The mid-term trophozoite, when it predominated in the blood at the
      time of treatment, was shown to be as sensitive to chloroquine as Plasmodium
      vinckei petteri. According to previous results indicating that part of the
      population of merozoites is latent and penetrates around midnight, the
      inoculations were timed in order to obtain a lower or higher degree of
      synchronisation. The infection appeared to be better synchronised if rings and
      young trophozoites, were inoculated at 06:00 hrs rather than at 15:00 hrs and
      consequently the efficacy of chloroquine was higher in the former than in the
      latter.

PMID- 9140490
TI  - Plasmodium vinckei vinckei, P. v. lentum and P. yoelii yoelii: chronobiology of
      the asexual cycle in the blood.
AB  - The biological rhythms of Plasmodium vinckei vinckei, P. v. lentum and P. yoelii
      yoelii i.e. synchronicity, duration of the erythrocytic cycle, timing of the
      schizogony and of the penetration of merozoites into red blood cells, were
      studied in the Swiss white mouse. Two different methods of synchronisation were
      used: the freezing-thawing of parasitized blood and the inoculation of a single
      parasitic stage, separated from the other stages by centrifugation through a
      Percoll-Glucose gradient. The duration of the schizogonic cycle of P. v. vinckei
      and P. v. lentum, two highly synchronous subspecies, was 24 hours. With P. v.
      vinckei the timing of the schizogony was independent of the circadian rhythm of
      the host and was set by the time of inoculation. With P. v. lentum the timing of
      the schizogony and merozoites penetration into red blood cells depended both, on
      the hosts rhythm and the time of inoculation of frozen-thawed blood: schizogony
      occurred at 18:00 if the inoculum was injected at 06:00 or 12:00 and at 06:00 if
      injected at 18:00 or 00:01. P. y. yoelii a naturally asynchronous parasite was
      synchronized by means of a Percoll-Glucose gradient. The duration of its
      intraerythrocytic cycle was found to be 18 hours, similar to that of the other
      subspecies of P. yoelii.

PMID- 9140491
TI  - Larval biology of six filariae of the sub-family Onchocercinae in a vertebrate
      host.
AB  - The development of six filariae of the sub-family Onchocercinae-Litomosoides
      sigmodontis, Acanthocheilonema viteae, Molinema dessetae, Monanema martini,
      Brugia malayi, B. pahangi-was compared in rodents, following a single inoculation
      of a low or high dose of infective larvae. Analysis was done with 105 rodents
      dissected and 53 rodents fixed for histopathology. The percentage of larvae which
      developed corresponded to the proportion of those which were able to penetrate
      into the sub-cutaneous lymphatic vessels; this percentage was determined during
      the first day (phase 1) and was characteristic of the filaria-host pair, and
      independent of the number of larvae inoculated. It could remain stable for a long
      time, more than eight months with M. martini (phase 2); the phenomena of
      regulation appeared later (phase 3). The larvae migrated through the lymphatic
      system, which represents a medium less protected and thus less aggressive than
      the blood system. The coelomic cavities, almost devoid of inflammatory cells,
      represented an ultimate shelter, as well as the joint-cavities (colonized by some
      Dirofilariinae). Localizations in the cardio-pulmonary blood system were
      accidental and occurred when, during the migrations, some larvae penetrated into
      the thoracic channel and arrived in the superior vena cava, then the right
      ventricle and the pulmonary arteries (the biology of Dirofilaria immitis resulted
      in a secondary adaptation); such accidents may occur with adult filariae,
      especially, after drug treatment. One may expect similar events in human
      filariasis. These "occult" filariae, more frequent than it is usually thought,
      influence the immunological status and the pathology.

PMID- 9140492
TI  - Molecular phylogenetic studies on Brugia filariae using Hha I repeat sequences.
AB  - This paper is the first molecular phylogenetic study on Brugia parasites (family
      Onchocercidae) which includes 6 of the 10 species of this genus: B. beaveri Ash
      et Little, 1964; B. buckleyi Dissanaike et Paramananthan, 1961: B. malayi (Brug,
      1927) Buckley, 1960; B. pahangi (Buckley et Edeson, 1956) Buckley, 1960; B. patei
      (Buckley, Nelson er Heisch, 1958) Buckley, 1960 and B. timori Partono et al.,
      1977. Hha l repeat sequences are 322 nucleotides long, highly repeated, tandemly
      arranged and unique to the nuclear genomes of the genus Brugia. Hha l repeat
      sequence data was collected by PCR, cloning and dideoxy sequencing. The Hha l
      repeat sequences were aligned and analyzed by maximum parsimony algorithms,
      distance methods and maximum likelihood methods to construct phylogenetic trees.
      Bootstrap analysis was used to test the robustness of the different phylogenetic
      reconstructions. The data indicated that the Hha l repeat sequences are highly
      conserved within species yet differ significantly between species. The various
      tree-building methods gave identical results. Bootstrap analyses on the Hha l
      repeat sequence data set identified at least two clades: the B. pahangi-B.
      beaveri clade and the B. malayi-B. timori-B. buckleyi clade; the first clade
      includes parasites of carnivores from Asia and America; the second includes
      species from primates and lagomorphs from Asiatic region. It was also noted that
      the Hha l repeat sequences obtained from B. malayi were identical to those
      obtained from B. timori, indicating very recent speciation.

PMID- 9140493
TI  - Specific cellular and humoral immune responses induced by different antigen
      preparations of Echinococcus multilocularis metacestodes in patients with
      alveolar echinococcosis.
AB  - A specific proliferation of the peripheral blood mononuclear cells (PBMC)
      stimulated by antigens of Echinococcus sp. has been shown in patients with cystic
      as well as alveolar echinococcosis. However, the development of a major
      granulomatous reaction around the parasitic larvae is a characteristic feature of
      the local immune response to E. multilocularis while humoral immune responses
      seem to predominate in E. granulosus infection. The aim of this study was to
      analyse the specific proliferation of the PBMC from 36 patients with alveolar
      echinococcosis, and 23 controls, induced by a crude preparation of E.
      multilocularis (EmcAg) as well as by two E. multilocularis specific antigen
      preparations, the Em2 antigen and the protoscolex (ESAg) antigen. The significant
      correlation observed between the proliferation index either by Em2 and ES or by
      Emc suggests that both antigens account for an important part of the lymphocyte
      proliferative response. The strong effect of these species specific antigens on
      lymphocyte proliferation is confirmed by the comparison of the results obtained
      in this study to those obtained in a previous study of specific cellular immunity
      to E. granulosus antigens in patients with cystic echinococcosis. The
      proliferation indices were significantly elevated in all those 7 patients with a
      proven AE who were sero-negative using the Emc ELISA as well as in the 12
      patients also seronegative, but using the Em2 ELISA. In 5 seronegative patients
      who had had a complete resection of the parasitic lesions two years before the
      lymphocyte proliferation evaluation, the PI was above the threshold value for two
      dilutions of EmcAg. PI under the threshold values were obtained only in patients
      with residual lesions. These results suggest that E. multilocularis specific
      antigens promote the proliferation of lymphocytes which could be TH1 cells,
      responsible for the intense periparasitic granulomatous reaction characteristic
      of alveolar echinococcosis.

PMID- 9140494
TI  - Seasonal occurrence and maturation of Neoechinorhynchus rutili (Acanthocephala)
      in barbel, Barbus barbus (Pisces), of the Jihlava River, Czech Republic.
AB  - From April 1992 until June 1993, the seasonal occurrence and maturation of the
      acanthocephalan Neoechinorhynchus rutili in its definitive host, the barbel
      (Barbus barbus), was studied in the Jihlava River (the Danube basin), Czech
      Republic. The parasite occurred in barbel throughout the year (overall prevalence
      84% and intensity of infection 1-533 [mean 25] acanthocephalars per fish), but
      there were distinct seasonal fluctuations in prevalence and mean intensity
      values: prevalence attained 100% in February and March, whereas its lowest value
      was recorded in July; the lowest values of mean intensity occurred in July
      August. Both prevalence and mean intensity values distinctly increased with the
      body length of hosts. The parasite exhibited a distinct annual maturation cycle
      when egg-producing females were present mainly in the spring and summer (May
      July) and, at a lesser extent, also from December to April of the next year. The
      seasonal maturation of N. rutili appears to be induced principally by the
      temperature regimen in the locality. N. rutili cystacanths were recovered from
      larval Sialis lutaria (Megaloptera) (prevalence 6%).

PMID- 9140495
TI  - First cases of gynandromorphism in Phlebotomus perniciosus Newstead 1911
      (Diptera, Psychodidae, Phlebotominae).
AB  - Two gynandromorphic specimens of Phlebotomus perniciosus Newstead, 1911 are
      described and illustrated for the first time. The specimens were collected in the
      Northeast of the Iberian Peninsula (Spain).

PMID- 9140496
TI  - Falciparum malaria: IX. Bone marrow changes mimicking malignant histiocytosis. A
      case report.

PMID- 9140497
TI  - Parasitic effects on host life-history traits: a review of recent studies.
AB  - We review empirical studies bearing on the effects of parasites on the age of
      maturity of their hosts. The few cases already published support theoretical
      predictions, namely a decrease of host prereproductive life-span unless parasites
      are benign. Host responses may be due either to phenotypic plasticity or to
      genetic differences, and even though very few studies on this topic have already
      been published both mechanisms occur. Promising areas of research include the
      distribution of age-specific potential costs of resistance to parasitism, as well
      as the evolution of age-specific parasite preferences under the concomitant
      evolution of host life-history traits.

PMID- 9140498
TI  - A laboratory model of canine leishmaniasis: the inoculation of dogs with
      Leishmania infantum promastigotes from midguts of experimentally infected
      phlebotomine sandflies.
AB  - Twenty-five dogs (beagles) were infected with Leishmania infantum by the
      intradermal inoculation of an estimated 5-8,000 metacyclic promastigotes
      harvested from the midguts of 320 experimentally infected P. perniciosus. Details
      are given of the methods of infecting the flies and harvesting the parasites. All
      dogs developed small, self-healing chancres at the sites of inoculation.
      Parasites were isolated from lymph nodes, bone marrow or spleen of 21 dogs, 12 of
      which developed signs of disease and raised IFAT litres to Leishmania. Nine of
      the 21 remained healthy over a five-year observation period. Six of the nine were
      shown to have a cell mediated immune response to Leishmania. No parasites were
      isolated from four of the 25 dogs, two of which had a demonstrable cell mediated
      immunity and another had low transitory IFAT titres. The fourth had chancres at
      the sites of inoculation. The results show that dogs can be readily infected with
      promastigotes from the midguts of sandflies. However, a high proportion develop a
      cell mediated immunity and show on signs of disease. It is suggested that
      serological surveys of dogs for canine leishmaniasis reveal neither the true
      prevalence of infection nor the intensity of transmission. The efficacy of
      controlling human visceral leishmaniasis caused by L. infantum by destroying
      seropositive dogs is questioned.

PMID- 9140500
TI  - An ultrastructural study on the early cellular response to Dirofilaria immitis
      (Nematoda) in the Malpighian tubules of Aedes aegypti (refractory strains).
AB  - Dirofilaria immitis living in Aedes aegypti refractory strains were studied in
      relation to ultrastructural events in primary cells of Malpighian tubules and to
      defense mechanisms activated by host-cells. When the microfilaria reaches the
      Malpighian cells, its intracellular development is blocked by defense mechanisms
      activated by the host, resulting in lysis of the outermost cuticle of the
      parasite without melanin involvement. Ultrastructural evidence suggests that
      lysis is brought about by Malpighian cell products.

PMID- 9140499
TI  - Action of pentamidine-bound nanoparticles against Leishmania on an in vivo model.
AB  - The efficiency of antileishmanial agents may be enhanced by improving their
      bioavailability with a colloidal drug carrier. We have investigated the action of
      free pentamidine, compared with pentamidine bound to polymethacrylate
      nanoparticles, in a rodent model. BALB/c mice were infected, via the tail vein,
      with 4 x 10(7) L. major (MON 74) promastigotes. Twelve days after infection,
      seven groups of mice were treated respectively with methylglucamine antimoniate
      (Glucantime) 5.56 mg/kg i.p. x 5 d., pentamidine bound nanoparticles (100
      microM), unloaded polymethacrylate nanoparticles, unloaded nanoparticles
      associated with free pentamidine (100 microM) 0.1 ml i.v. x 3 d and free
      pentamidine isethionate (2.28 mg/kg and 0.17 mg/kg i.v. x 3 d.). Twenty-one days
      post infection, the mice were sacrificed and the Leishmania load in the liver
      calculated from the number of amastigotes/500 liver cells and total liver weight
      in treated and untreated mice. Results demonstrated a 77% amastigote reduction in
      the group treated with targeted pentamidine relative to the control group. The
      ratio free pentamidine/bound-pentamidine was approx. 12.

PMID- 9140501
TI  - Onchocerca suzukii n. sp. and O. skrjabini (= O. tarsicola) from a relict bovid,
      Capricornis crispus, in Japan.
AB  - The species from the tendons and sub-cutaneous tissue of the tarsal and carpal
      joints is identified as O. skrjabini Rukhlyadev, 1964 (this taxon, which was
      poorly defined and badly restored, is used instead of O. tarsicola to avoid
      dispute). O. skrjabini belongs to on homogeneous group of four species parasitic
      in Palearctic cervids, which seems to have evolved relatively recently. The
      morphological characteristics of the parasite of Capricornis are not sufficient
      to warrant the creation of a new taxon. The species from the subcutaneous tissue
      of the body is named O. suzukii n. sp. It belongs to a group comprising three
      species, parasites of antilocaprids and cervids from the Holarctic region and
      tropical domestic bovines, which seem to have evolved before the skrjabini group.
      The Japanese species does not present the hypertelic characters of the other
      species of the group. The microfilaria of O. suzukii is unknown. Thus it is not
      possible to say if this species is the same as one found in bovines (and,
      perhaps, in humans) in the Oita region of Kyushu Island.

PMID- 9140502
TI  - Pulmonary dirofilariasis in man: a new Italian case. Review of the European
      literature.
AB  - In June 1991 a 62-year-old retired man, from Udine (northern Italy), was suddenly
      affected by dyspnoea. X-ray and CT control detected a coin lesion in the lung, in
      May 1992 this lesion was removed surgically. Histological examination revealed
      the presence of a nematode inside an arteriole which had provoked a small infarct
      in the pulmonary tissue. The parasite presented marked regressive phenomena that
      made an accurate morphological analysis impossible. However, in the light of
      certain details of the cuticle, and by analogy with four similar cases occurring
      in northern Italy, as well as 10 others (nine subcutaneous and one submucosa)
      reported in man from the same region (Venetia) over the last 15 years, the
      aetiologic agent was thought to be Dirofilaria (N.) repens. Over all 10 cases of
      human pulmonary dirofilariasis were reported in Europe: five in Italy, probably
      by D (N.) repens, two in Germany, in patients coming from Corsica and two in
      Spain (only by serology), attributed to D. immitis. In addition one case was
      reported in U.S.A. in a man who previously visited Italy.

PMID- 9140503
TI  - Intestinal co-infection by Cyclospora sp. and Cryptosporidium parvum: first
      report in an AIDS patient.
AB  - Cyclospora is recently described new human pathogenic coccidian causing
      intermittent diarrhoeal enteritis which may persist for weeks or months in
      immunocompetent subjects, particularly travellers visiting some tropical areas
      and countries, such as Nepal, the Caribbean, Peru and Mexico. More rarely this
      enteric pathogen affects immunocompromised humans, namely HIV-infected people or
      AIDS patients, with some clinical pictures recognized in normal hosts. We
      describe the first case of Cyclospora sp. and Cryptosporidium parvum associated
      diarrhoeal enteritis in an adult AIDS patient.

PMID- 9140504
TI  - The isolation of Leishmania donovani MON-18, from an AIDS patient in Portugal:
      possible needle transmission.
AB  - The spread of HIV infection into leishmaniasis endemic areas has increased the
      incidence of immunosupressed patients with kalaazar in Portugal. The dermotropic
      zymodeme MON-24 of leishmania infantum has been already isolated from a
      Portuguese AIDS patient, as in some other Mediterranean countries. In this paper
      we report the isolation of L. donovani MON-18 from a drug addicted Portuguese
      patient with clinical visceral leishmaniasis and AIDS, that suggests a
      mechanically transmitted infection by the use of a shared needle or syringe.

PMID- 9140505
TI  - A giant merogonial stage (Apicomplexa, Coccidia) in the intestine of Blicca
      bjoerkna (L.) (Cyprinidae).
AB  - A giant meront containing thousands of merozoites has been found in the
      intestinal epithelium of an adult specimen of white bream (Blicca bjoerkna). The
      taxonomic position of this unusual coccidian stage is discussed.

PMID- 9140506
TI  - Immunocytochemical study of tissue parasitism of dog adrenal glands in
      experimental Chagas' disease.
AB  - In human beings, the central vein of the adrenal glands has been considered by
      some authors to be one of the preferential sites of Trypanosoma cruzi settling in
      the chronic form of Chagas' disease. This appears to be due to the local
      corticoid-rich environment that may protect the parasite against the
      immunological defences of the host. An immunocytochemical study of the adrenal
      glands of 15 dogs was carried out for the detection of tissue parasitism in the
      acute and chronic phases of experimental T. cruzi infection. No amastigote nests
      or isolated amastigotes were detected in the adrenal parenchyma or adrenal
      central vein of the animals studied. Minimal nonspecific inflammatory changes
      were found in some glands of both infected and noninfected animals. The present
      results show that the adrenal glands of the dog are not injured and do not
      constitute a site of escape or reservoir of parasites in experimental Chagas'
      disease.

PMID- 9140507
TI  - Fasciola hepatica: a study of the shedding of cercariae from Lymnaea truncatula
      raised under constant conditions of temperature and photoperiod.
AB  - Investigations on the shedding of cercariae of Fasciola hepatica were carried out
      in Lymnaea truncatula in order to verify the existence of a low-frequency
      periodicity in the numerical distribution of metacercariae per snail and per day
      when the snails are raised under controlled conditions. Preadult L. truncatula
      were thus collected in the field, individually exposed to two miracidia, and
      subsequently raised until their death under constant temperature (20 degrees C)
      and photoperiod (12 h/12 h diurnal rhythm). The 102 snails shedding parasites
      produced 24,325 metacercariae of which 5% were floating cysts. The daily
      production of cercariae was maximal during the first 30 days of the patent
      period, subsequently decreased until day 114, and ceased on day 124. No infradian
      type rhythm was noted in the daily distribution of mean values. The snails shed
      their cercariae in one to 14 waves; 20.6% and 15.7% of the snails produced their
      parasites in four and five periods respectively. The authors suggest that the
      seven-day periodicity found by Audousset et al. (1989) in the daily distribution
      of cercariae produced by three colonies of L. truncatula raised in seminatural
      conditions must be attributed only to the influence of environmental factors.

PMID- 9140508
TI  - Transmission of Anaplasma marginale with adult Boophilus microplus ticks fed as
      nymphs on calves with different levels of rickettsaemia.
AB  - Nine splenectomised calves were infested with dissimilar numbers of adult
      Boophilus microplus ticks 72 h after collection as engorged nymphs from three non
      splenectomised calves with different levels of Anaplasma marginale rickettsaemia.
      Successful transmission of A. marginale appeared to be more dependent on the
      level of rickettsaemia of the donor calves than on the number of ticks attaching
      to the splenectomised calves, since infection was transmitted only when the
      rickettsaemia was 0.3% or greater. Field transmission would thus depend on the
      rate of tick migration amongst susceptible hosts and the rickettsaemia level of
      cattle on which the ticks fed previously.

PMID- 9140509
TI  - The effects of malaria control on nutritional status in infancy.
AB  - Both malaria and undernutrition are major causes of paediatric mortality and
      morbidity in sub-Saharan Africa. The introduction of insecticide-treated bed nets
      (ITBN) during a randomized controlled trial on the Kenyan coast significantly
      reduced severe, life-threatening malaria and all-cause childhood mortality. This
      paper describes the effects of the intervention upon the nutritional status of
      infants aged between 1 and 11 months of age. Seven hundred and eighty seven
      infants who slept under ITBN and 692 contemporaneous control infants, were seen
      during one of three cross-sectional surveys conducted during a one year period.
      Standardized weight-for-age and mid-upper arm circumference measures were
      significantly higher among infants who used ITBN compared with control infants.
      Whether these improvements in markers of nutritional status were a direct result
      of concomitant reductions in clinical malaria episodes remains uncertain. Never
      the-less evidence suggests that even moderate increases in weight-for-age scores
      can significantly reduce the probability of mortality in childhood and ITBN may
      provide additional gains to child survival beyond their impressive effects upon
      malaria-specific events.

PMID- 9140510
TI  - Repetitive dosing of artemisinin and quinine against Plasmodium falciparum in
      vitro: a simulation of the in vivo pharmacokinetics.
AB  - Plasmodium falciparum (F32) parasites were exposed to artemisinin and quinine for
      3 and 4 h, respectively, once or twice daily and for 3, 5 or 7 days. Between the
      peaks the parasites were exposed to trough concentrations. Continuous drug
      exposure was also assessed for comparison. After drug exposure, the cultures were
      extended for an observation period of up to 30 days to assess the viability of
      the parasites remaining after drug exposure. For artemisinin, a critical
      threshold concentration of 3 x 10(-8) M was required for growth inhibition.
      Dosing twice daily for at least 5 days was also critical. Prolonging the duration
      of drug exposure to 7 days further increased the efficacy. For quinine the
      results were quite different. The concentration dependency of the efficacy was
      more gradual. On the other hand dosing once daily appeared to be nearly as
      effective as twice daily and radical clearance was obtained even after 3 days of
      exposure at peak concentrations of 10(-5) M. A concentration of 10(-6) M provided
      the same effect if the duration was extended to 7 days. There was a strong
      similarity between estimated concentrations of free unbound drug required for
      radical clearance in vitro and those empirically required for clinical efficacy
      in vivo. This suggests that the in vitro model represents an appropriate model
      for estimating drug efficacy and pharmacodynamics if the in vitro system is
      adapted to simulate in vivo pharmacokinetics.

PMID- 9140511
TI  - Prophylactic effects of isometamidium- and ethidium-sustained release devices
      against Trypanosoma congolense in cattle.
AB  - Two successive experiments were carried out in which three cows were treated by
      intramuscular injection of either 0.5 mg/kg isometamidium or 1 mg/kg ethidium and
      compared with another group of three cows which received a subcutaneously
      implanted sustained release device (SRD) containing the same dose of drug. The
      prophylactic effect of both drug formulations was evaluated by exposing the
      animals at monthly intervals to Glossina morsitans morsitans infected with
      Trypanosoma congolense. The average protection period using the isometamidium-
      and the ethidium-SRD was extended by a factor of 3.2 and 2.8, respectively in
      comparison with the intramuscular injection of the drugs. In the analysis of
      isometamidium concentrations in the serum of the animals using a competitive drug
      ELISA the drugs remained present for much longer periods in the sera of the
      implanted animals than in those of the intramuscularly treated cattle. The
      animals were still protected, however, a long time after the disappearance of
      detectable drug levels in the serum. No difference in drug sensitivity could be
      observed, when breakthrough isolates were compared from animals which received
      the ethidium-SRD and those treated intramuscularly, although a slight loss
      sensitivity occurred in the breakthrough isolates as compared to the parent
      trypanosome population.

PMID- 9140512
TI  - Nutrient content and survival of selected pathogenic bacteria in kenkey used as a
      weaning food in Ghana.
AB  - Kenkey is a cooked, fermented white maize food of the people of the southern half
      of Ghana. There are three types of kenkey viz: Ga, Fanti-Brown and Fanti-White.
      Kenkey is widely used as a weaning pap by a lot of low income families. In
      mashing it into the weaning pap, mothers use their bare hands. This and the use
      of untreated water, especially in rural communities, introduce the risk of
      microbial contamination. Kenkey's nutritional contribution to the weanling and
      the survival of selected pathogenic bacteria in kenkey's milieu were investigated
      in this study. Crude Protein (CP) was determined by the Kjedahl method. Atomic
      absorption spectrophotometry was used to determine levels of minerals.
      Escherichia coli (1955 and 101,685), Klebsiella pneumoniae and Staphylococcus
      aureus populations in kenkey milieu of pH 4 were monitored over a period of time.
      Our results suggested that, nutritionally, Ga kenkey is the best of the three
      types of kenkey. A weanling of 9 kg body weight is maximally offered 450 g of
      kenkey a day. This weight of kenkey offers the following levels of nutrients on
      as-it-is or wet basis: CP, 13.13 g and dry matter (DM), 141.14 g. Minerals levels
      were P, 266.22 mg; Ca, 14.1 mg; K, 451.94 mg; Na, 1301.15 mg; Mg, 260 mg; Fe,
      8.65 mg; Zn, 3.91 mg; Cu, 0.23 mg; Mn, 1.15 mg; Co, 0.6 mg; and Cr, 0.36 mg.
      These values did not satisfy the recommended daily dietary allowances (RDAs) for
      weaning. The populations of our test pathogenic bacteria were reduced by 1-3 logs
      in 30 min in Ga kenkey milieu of pH 4. In using kenkey for weaning purposes,
      therefore, breastfeeding and selected nutrient supplementation are necessary to
      avert malnutrition. Since the extent of microbial reduction on exposure to a
      lethal agent also depends on the initial microbial load, mothers should wash
      their hands very well to reduce microbial loads before using them to mash kenkey.
      They should also use treated water and heat the kenkey pap before serving.

PMID- 9140513
TI  - Competence of a migratory bird, red-bellied thrush (Turdus chrysolaus), as an
      avian reservoir for the Lyme disease spirochetes in Japan.
AB  - To evaluate the competence of migratory birds as reservoirs for the Lyme disease
      spirochetes, we examined two species of migrants, Red-bellied thrush (Turdus
      chrysolaus) and Black-faced bunting (Emberiza spodocephala) in Nemuro, the
      northern part of Japan. Spirochetes were found in four individual birds out of 11
      T. chrysolaus, three isolates were detected from the skins and the other one was
      obtained from the liver. No spirochete was found to be infected in 20 E.
      spodocephala. As far as we know, this is the first record of direct detection of
      the spirochetes from migratory birds in Japan. The spirochetes were also isolated
      from immature ixodid ticks, Ixodes persulcatus, fed on those species of birds.
      The spirochetes were transmitted trans stadially to the next stage, when infected
      ticks molted. All of the isolates from birds and ticks were identified as
      Borrelia garinii by our ribotyping and flagellin gene sequence analyses. Our
      results strongly suggest that the migratory birds are reservoirs in the
      transmission of the Lyme disease spirochetes in Japan.

PMID- 9140514
TI  - Effective non-radioactive method of surface labeling Cryptosporidium parvum
      sporozoites.

PMID- 9140515
TI  - Epithelium, microcirculation, and eosinophils--new aspects of the allergic airway
      in vivo.

PMID- 9140516
TI  - Susceptibility genes for allergy and asthma.

PMID- 9140517
TI  - Specific immunotherapy with Dermatophagoides pteronyssinus and D. farinae results
      in decreased bronchial hyperreactivity.
AB  - To evaluate the tolerability and efficacy of specific immunotherapy with mite
      extracts, we performed a double-blind, placebo-controlled immunotherapy study in
      30 patients with proven allergy to mite allergens. The specific immunotherapy
      with standardized extracts of Dermatophagoides pteronyssinus and D. farinae by a
      clustered rush protocol was well tolerated. After 1 year of treatment, the
      actively treated group showed a significant improvement compared to their
      starting value as well as to the placebo-treated patients with regard to skin
      prick test, conjunctival provocation test, and subjective rhinitis score. The
      subjective asthma score and bronchial hyperreactivity, measured by the
      methacholine provocation test, was improved in comparison to the starting value,
      but not to the placebo group, after 12 months. However, a further, open
      comparison of the placebo- and verum-treated groups at 18 months revealed a
      significant reduction. The drug intake was not increased in the verum-treated
      group. Exposure to mite levels was constant throughout this time period, as
      revealed by antigen measurement. We conclude that specific immunotherapy in
      perennial, mite-allergen-induced asthma may reduce not only immediate, IgE
      mediated symptoms but, after a rather long time period of 12-18 months, also the
      inflammatory component of bronchial asthma, thus leading to a reduction of
      unspecific hyperreactivity.

PMID- 9140518
TI  - A preceding airway reaction to one allergen may lead to priming of the airway
      responses to another allergen.
AB  - This study aimed to determine whether a preceding airway response to one allergen
      leads to priming of the airway responses to another allergen. Twelve asthmatic
      children who had positive prick tests to two allergens, Dermatophagoides
      pteronyssinus (D.p.) and German cockroach (CR), participated in a randomized,
      placebo-controlled crossover study. We performed two consecutive inhalation
      challenges, D.p. challenge being followed 48 h later by CR challenge. The effect
      of initial (D.p.) challenge on the early and late airway responses to the
      subsequent (CR) challenge (CR2) was examined by comparing the responses with
      those to CR challenge preceded by sham challenge (CR1). The geometric mean PD20
      of CR allergen in the CR2 was 2.8 BU (breath unit) (range of 1 SD; 0.77-10.4),
      which was 12.0-fold less than that (33.7 BU, 10.8-105.2) in the CR1. The
      administration of a 6.1-fold less dose (8.9 BU, 2.7-28.8) in the CR2 than in the
      CR1 (54.5 BU, 44.1-69.3) provoked a similar degree of late-phase reactions (18.7
      +/- 7.3% vs 15.8 +/- 9.6%). Our data indicated that the early- and late-phase
      reactions to CR challenge were augmented by the preceding reaction to D.p. This
      suggests that a preceding airway response to one allergen may lead to priming,
      with enhancement of the early and late airway responses to the subsequent
      challenge with another allergen.

PMID- 9140519
TI  - Allergenicity of alpha-caseins from cow, sheep, and goat.
AB  - The allergic potential of alpha-caseins from bovine, ovine, and goat's milk
      sharing more than 85% identical amino acids was compared. Caseins were purified
      by anion-exchange chromatography and used for a specific IgE and IgG ELISA with
      diluted human sera. Sera were from 17 children with immediate-type allergy to
      cow's milk, from 59 children with atopy but without food allergy, and from 27
      healthy children without atopy disease. The sera of cow's milk-allergic children
      showed a significantly higher IgE and IgG binding to alpha-caseins from all three
      species than the sera of the other groups. All groups showed an increased
      antibody binding to bovine alpha-casein compared to the sheep and goat proteins,
      but the differences were significant only in the groups of atopic children and of
      healthy controls. Furthermore, inhibition of the IgE binding to bovine alpha
      casein with alpha-casein from cow, goat, and sheep revealed that the alpha-casein
      from these species are highly cross-reactive; on the basis of the small
      differences in their primary structure. In conclusion, the milk of goat and sheep
      harbor an allergic potential and is not suitable for the nutrition of milk
      allergic patients.

PMID- 9140520
TI  - Mattresses as a winter refuge for house-dust mite populations.
AB  - House-dust mites are a major source of allergens. Beds are often heavily
      infested. It is conceivable that, during the winter period in temperate climates,
      the ambient indoor air is too dry for their survival, but that mites can still
      survive in beds where the humidity is raised when the bed is occupied. To
      investigate whether house-dust mites can take advantage of daily episodes with
      elevated humidity to restore water balance, we exposed mites to spells of high
      humidity (90% relative humidity [RH]), lasting 0, 1.5, 3, 6, or 12 h, once every
      day, while the humidity was low (10% RH) during the rest of the time. Survival
      was markedly promoted when only 1.5 h of moist air per day was given. Three hours
      of moist air per day allowed the mites to reproduce. The same average humidity
      but at a constant level would have been lethal to the mites. Thus, average
      humidity can be misleading as an indicator of mite survival conditions.
      Measurements of relative humidity were made inside the foam core of a mattress
      and underneath the ticking. The rise of humidity occurring when the bed was
      occupied was often insufficient for the mites, because the temperature rose at
      the same time. At higher temperatures, mites required a higher relative humidity,
      abolishing the effect of the simultaneous rise in absolute humidity. Thus, it
      seems quite possible to regulate house-dust mite numbers also in beds by reducing
      the water content of the ambient air. The rules governing changes in temperature
      and humidity inside a bed may be simple enough to allow assessment of house-dust
      mite living conditions by measurements in the ambient air.

PMID- 9140521
TI  - Latex allergen elimination in natural latex sap and latex gloves by treatment
      with alkaline potassium hydroxide solution.
AB  - Antigenic proteins in latex products can cause type I allergy. We investigated
      the effects of potassium hydroxide (KOH) solution on the allergenicity of
      proteins in natural latex sap and latex gloves by using an EAST competitive
      inhibition immunoassay and skin prick test. Latex sap was mixed with KOH solution
      at different concentrations and incubated over various periods of time at room
      temperature. Latex gloves were washed in KOH solution for different times at 30
      degrees C and 90 degrees C. Our immunoassay results for the subsequently
      extracted latex proteins demonstrated a KOH concentration-, temperature-, and
      time-dependent decrease in allergenicity, finally resulting in complete loss of
      IgE-binding activity. In the skin prick test, we found only four weakly positive
      reactions to proteins extracted from KOH-washed gloves in 30 latex-sensitized
      patients. In addition, up to 97% of the aqueous extractable protein content could
      be removed from latex gloves by washing in KOH solution under certain conditions.
      These results suggest that antigenic proteins in natural latex sap and latex
      gloves can be changed by treatment with KOH solution, which is followed by a loss
      of their capability to bind specific IgE antibodies from most latex-sensitized
      patients.

PMID- 9140522
TI  - Low-dose cyclosporin A in the treatment of severe chronic idiopathic urticaria.
AB  - In a limited number of severe chronic idiopathic urticaria (CIU) patients, low
      dose cyclosporin A (CsA) treatment was found to be effective. This open study
      aimed to extend this clinical observation and determine the safety of treatment
      with CsA. In addition, it aimed to determine the prevalence and characteristics
      of the autologous serum skin test (AST) in such patients, and whether this test
      is affected by CsA treatment. Thirty-five patients who suffered from severe CIU
      (score 3), and who were followed for 6 months (using a clinical urticaria
      severity score [range 0-3]) were divided into three groups: 19/35 were treated
      for 3 months with low-dose CsA, and thereafter followed for an additional 3
      months; 6/35 dropped out of protocol treatment; and 10/35 untreated patients
      (followed for the same period) served as a disease controls. In the treated
      group, no side-effects were observed, and by the end of treatment, 13/19 (68%)
      patients were in full remission (score 0) and the remainder scored 1. In
      contrast, the 10 CsA-untreated patients scored 3 for the whole follow-up period
      of 6 months. Positive AST was found in 14/35 (40%) of patients, whereas none were
      detected in 20 healty control subjects. AST neither correlated with disease
      activity nor predicted response to treatment. This uncontrolled study shows that
      low-dose CsA is effective in treating CIU patients, and can be given safely for 3
      months. However, CIU patients requiring initially high doses of
      glucocorticosteroids and with a long clinical history are less amenable to CsA
      treatment.

PMID- 9140523
TI  - Eosinophilopoietic factors prime eosinophils for increased interleukin-8
      generation.
AB  - Recent studies have identified eosinophils as a cellular of various cytokines,
      indicating that eosinophils play not only an effector role but also a regulatory
      role within the allergic inflammatory cell network. Because eosinophilopoietic
      factors are known to stimulate various functions of eosinophils, we examined the
      effect of interleukin (IL)-5 on chemoattractant-induced IL-8 generation from
      eosinophils. Although IL-5 alone induced little or no IL-8 production from
      eosinophils, short-term preincubation with IL-5 markedly enhanced the eosinophil
      IL-8 generation caused by C5a plus cytochalasin B (CB). IL-3 also potentiated C5a
      induced IL-8 generation. Both factors were active at picomolar concentrations.
      Furthermore, competitive polymerase chain reaction (PCR) experiments revealed
      that the enhancement occurred at the pretranslational level. Since eosinophils in
      allergic inflammation are believed to be activated by these eosinophilopoietic
      factors, eosinophil-derived cytokines may play more important roles in the
      allergic inflammatory cell network than has been previously supposed.

PMID- 9140524
TI  - Allergenicity of the pollen of Pistacia.
AB  - Differences in IgE binding and skin responses to pollen extracts of four species
      of Pistacia, and some immunochemical characteristics of this pollen were
      investigated. The incidence of positive SPT among atopic patients varied between
      31.5% to the pollen extracts of P. vera and 24.6% to P. palaestina. The antigens
      are located on the exine of the grains as well as in their cytoplasm. Some of the
      antigens are common to all four species, whereas others seem to be specific.
      Cross-reactivity was found among the four species of Pistacia and between them
      and Schinus terebintifolious. Five conspicuous IgE-binding bands were observed in
      the immunoblots of the four examined species, the bands of 49, 57, 64, 68, and 79
      kDa. The 36-37-kDa band of P. lentiscus and the 60- and 84-kDa bands of P.
      atlantica and P. vera were also noticeable. As the flowering seasons of Pistacia
      and Schinus do not overlap, the patients are exposed to such pollen for more than
      4 months a year. Apparently, Pistacia pollen is a major source of allergy.

PMID- 9140525
TI  - The natural course of allergic rhinitis during 12 years of follow-up.
AB  - As symptoms of allergic rhinitis are generally thought to disappear with
      increasing age, we decided to follow up our allergic rhinitis patients to
      ascertain whether their disease had regressed or progressed, and whether they had
      developed respiratory symptoms. At our department, between 1979 and 1982,
      allergic rhinitis was diagnosed in 108 patients. In 1993, 82 of the patients (40
      women, 42 men; mean age 36 years), none of whom had received immunotherapy,
      answered a questionnaire concerning the status of their allergic rhinitis, and
      any development of the disease during the interim. Of the 82 patients, one was
      free of allergic symptoms and 39% had become better; symptoms were unchanged in
      39% of cases, and worse in 21%. Six percent had suffered from asthma at
      presentation, 6% had developed asthma in the interim, and 34% reported other
      lower airways symptoms. Neither sex nor age at diagnosis was a determinant of the
      course of allergic rhinitis. Thus, in contrast to findings in other studies, the
      severity of allergic rhinitis seems to have increased among our patients.

PMID- 9140526
TI  - Food allergy to pumpkinseed--characterization of allergens.
AB  - In recent years, pumpkinseed has become increasingly popular as a foodstuff. Here
      we report the occurrence of allergic reactions (itching and swelling of oral
      mucosa, and asthma) to this member of the Cucurbitaceae family. We investigated
      three patients suffering from symptoms after ingestion of roasted pumpkinseed.
      All the patients fished for sport and used pressed pumpkinseed flour as bait.
      Sera were tested by the immunoblot technique for IgE reactivity with proteins of
      pumpkinseed extract. The immunoblot revealed pumpkinseed allergens of 13, 14, 36,
      48, 77, and 87 kDa. Inhibition experiments with recombinant birch profilin were
      performed: IgE binding to the 14-kDa allergen was completely blocked by
      preincubation of the sera with recombinant birch profilin. In conclusion, type I
      allergy to pumpkinseed is rare, and the patients' histories suggest inhalation of
      pumpkinseed flour during fishing to be the relevant route of sensitization,
      leading to food allergy to pumpkinseed.

PMID- 9140527
TI  - Nasal biopsy is superior to nasal smear for finding eosinophils in nonallergic
      rhinitis.
AB  - The presence of eosinophils was compared in nasal biopsy and smear. Thirty-two
      nonallergic rhinitis patients, of whom six had nasal polyps, were included in the
      study. The specimens were studied light-microscopically after staining with
      hematoxylin-eosin. The association between the presence of polyps and the finding
      of eosinophils in the biopsy specimens proved to be significant. Ten normal
      subjects served as controls. It was far more simple to detect eosinophils in the
      biopsy samples than in the nasal smears. When we considered biopsies with at
      least four eosinophils in four fields as hypereosinophilic, our group of patients
      contained 25% nonallergic rhinitis with eosinophilia syndrome (NARES) patients.

PMID- 9140528
TI  - Detection of mosquito saliva-specific IgE antibodies by capture ELISA.
AB  - We developed an IgE-capture ELISA and measured mosquito saliva-specific IgE
      antibodies in 27 children sensitive to mosquito bites. Children with large 15-min
      bite wheals had significantly higher (P < 0.0005) mosquito saliva-specific IgE
      levels than children with small wheals. In the latter group, the saliva-specific
      IgE level was significantly higher (P = 0.031) than the levels of six infants
      never exposed to mosquitoes. A positive correlation (r = 0.65; P = 0.0002) was
      found between the size of the 15-min wheal and the mosquito saliva-specific IgE
      antibody levels. These results further support the role of mosquito saliva
      specific IgE antibodies in the pathogenesis of mosquito-bite whealing. Compared
      to immunoblotting, IgE-capture ELISA provides a quantitative method to measure
      mosquito saliva-specific IgE antibodies.

PMID- 9140530
TI  - Banana allergy in infants.

PMID- 9140531
TI  - Changed allergy pattern in outpatients.

PMID- 9140529
TI  - Clinical responses to ingested fungal alpha-amylase and hemicellulase in persons
      sensitized to Aspergillus fumigatus?
AB  - alpha-Amylase and hemicellulase, derived from culture of Aspergillus species, are
      commonly added to flour as improvers during baking. Two cases of women
      occupationally sensitized to alpha-amylase who developed allergic symptoms after
      eating baked bread have been reported. With a randomized, controlled study
      design, we have investigated whether similar responses occur in those sensitized
      to Aspergillus species. Seventeen subjects with positive skin prick tests to
      Aspergillus fumigatus were studied. Symptomatic and physiologic responses after
      ingestion of bread baked with alpha-amylase and hemicellulase were compared, in a
      crossover fashion, with those after ingestion of bread baked without enzymes. No
      increase in respiratory or other symptoms, lung function, or nonspecific
      bronchial hyperreactivity was reported after ingestion of the enzyme-containing
      bread. We conclude that important clinical reactions to alpha-amylase and
      hemicellulase in baked bread do not frequently occur in those sensitized to
      Aspergillus species.

PMID- 9140532
TI  - Autoimmune vasculitis and aortic stenosis in aspirin-induced asthma (AIA).

PMID- 9140533
TI  - Angioedema of ACE inhibitors.

PMID- 9140534
TI  - Cypress allergy: an underestimated pollinosis.

PMID- 9140535
TI  - Soluble CD23 is increased in allergy.

PMID- 9140536
TI  - Genetic origins of the Japanese: a partial support for the dual structure
      hypothesis.
AB  - Based on the morphological characteristics of the skull and teeth, Hanihara
      ([1991] Japan Review 2:1-33) proposed the "dual structure model" for the
      formation of modern Japanese populations. We examine this model by dividing it
      into two independent hypotheses: 1) the Upper Paleolithic population of Japan
      that gave rise to the Neolithic Jomon people was of southeast Asian origin, and
      2) modern Ainu and Ryukyuan (Okinawa) populations are direct descendants of the
      Jomon people, while Hondo (Main Island)-Japanese are mainly derived from the
      migrants from the northeast Asian continent after the Aeneolithic Yayoi period.
      Our aim is to examine the extent to which the model is supported by genetic
      evidence from modern populations, particularly from Japan and other Asian areas.
      Based on genetic distance analyses using data from up to 25 "classic" genetic
      markers, we find first that the three Japanese populations including Ainu and
      Ryukyuan clearly belong to a northeast Asian cluster group. This negates the
      first hypothesis of the model. Then, we find that Ainu and Ryukyuans share a
      group contrasting with Hondo-Japanese and Korean, supporting the second
      hypothesis of the model. Based on these results, we propose a modified version of
      the dual structure model which may explain the genetic, morphological, and
      archaeological evidence concerning the formation of modern Japanese populations.

PMID- 9140537
TI  - Dental emergence among urban Zambian school children: an assessment of the
      accuracy of three methods in assigning ages.
AB  - In situations where birth records are unavailable and stated ages are unreliable,
      the emergence of the permanent dentition can serve as an indicator of age. Due to
      substantial variation in the timing of tooth emergence, a sample (n = 721) of
      Zambian school children, with known ages, was examined to provide a tooth
      emergence reference standard for the area. Three methods for assigning ages were
      utilized and their accuracy assessed. A random test sample was withheld from the
      original study in order to further evaluate the methods' accuracy. The three
      methods-1) number of teeth, 2) regression and 3) probit analysis-were applied to
      Zambian children, and estimates of age were made. Predicted ages were compared to
      actual ages to determine the percentage of accuracy in three categories-(+/-) .5,
      +/- 1.0 and +/- 2.0 years- and paired t-tests were conducted. Each of the three
      methods was then applied to the test sample, and their accuracy was evaluated in
      the same manner. Methods 1 and 2 were found to provide the higher percentage of
      correct ages within +/- .5 years, assigning roughly 39% of both male and female
      children within this increment. This was also the case at the next increment,
      with methods 1 and 2 assigning a higher percentage (66-76%) of children to the +/
      1.0 year category, while the accuracy of method 3 was quite a bit lower. The
      results for the test sample were very similar to those of the main sample. The
      overall accuracy of methods 1 and 2 was very similar in both the main and test
      samples, while method 3 had lower accuracy and t-tests indicated significant
      differences. Therefore, due to ease of application in the field setting, method
      1, mean age per number of teeth emerged, is the method of choice.

PMID- 9140538
TI  - Characteristic high- and low-frequency dental traits in sub-Saharan African
      populations.
AB  - In an earlier investigation (Irish [1993] Biological Affinities of Late
      Pleistocene Through Modern African Aboriginal Populations: The Dental Evidence
      [Ann Arbor: University Microfilms]), biological affinities of 32 sub-Saharan and
      North African dental samples were estimated using comparative analyses of 36
      dental morphological traits. Marked dental homogeneity was revealed among samples
      within each of the two geographic regions, but significant interregional
      differences were noted. Assuming dental phenetic expression approximates or is an
      estimate of genetic variation, the present study of 976 sub-Saharan-affiliated
      Africans indicates they are not closely related to other world groups; they are
      characterized by numerous morphologically complex crown and root traits. Turner
      ([1984] Acta Anthropogenetica 8:23-78; [1985] in R Kirk and E Szathmary (eds.):
      Out of Asia: Peopling the Americas and the Pacific [Canberra: The Journal of
      Pacific History], pp. 31-78; [1990] Am. J. Phys. Anthropol. 82:295-318; [1992]
      Persp. Hum. Biol. 2/Archaeol. Oceania 27:120-127; [1992] in T Akaszawa, K Aoki,
      and T Kimura (eds.): The Evolution and Dispersal of Modern Humans in Asia [Tokyo:
      Hokusen-Sha Publishing Co-], pp. 415-438) reports that Northeast Asian/New World
      sinodonts also have complex teeth relative to Europeans, Southeast Asian
      sundadonts, Australian/Tasmanians, and Melanesians. However, sinodonty is
      characterized by UI1 winging, UI1 shoveling, UI1 double shoveling, one-rooted
      UP1, UM1 enamel extension, M3 agenesis, and three-rooted LM1. Sub-Saharan peoples
      exhibit very low frequencies of these features. It is proposed that the
      collection of dental traits which best differentiate sub-Saharan Africans from
      other worldwide samples includes high frequencies of the Bushman Canine, two
      rooted UP1, UM1 Carabelli's trait, three-rooted UM2, LM2 Y-groove pattern, LM1
      cusp 7, LP1 Tome's root, two-rooted LM2, UM3 presence, and very low incidences of
      UI1 double shoveling and UM1 enamel extension. This suite of diagnostic traits is
      termed the sub-Saharan African dental complex.

PMID- 9140539
TI  - Dental size and shape in the Roman imperial age: two examples from the area of
      Rome.
AB  - Different socioeconomic strata of Roman imperial age are represented by two large
      dental samples recovered from archaeological excavations near Rome, Italy. Teeth
      are investigated for crown dimensions and morphological variants. One sample,
      comprising 1,465 permanent teeth, represents the rural town of Lucus Feroniae
      (LFR) and is mainly composed of slaves and war veterans. The other, comprising
      734 teeth from the Isola Sacra necropolis at Portus Romae (NIS), represents the
      "middle class" segment of an urban population. Both series show small dental
      dimensions and fit at the lower end of the trend toward dental reduction in
      Europe from the Upper Paleolithic to the historical times. The urban sample is
      less variable metrically and less sexually dimorphic than the rural one. The
      analysis of discrete crown traits shows absence of rare phenotypic variants in
      both series. The urban sample is also less variable in this last respect,
      suggesting that the gene pool of this particular "stratum" of the NIS population
      was more homogeneous than that of LFR. The occurrence of enamel hypoplasia
      indicates that metabolic stress during growth and development was similar in LFR
      and NIS. The overall set of available data is evaluated in the light of the
      history of the two Roman sites and the composition of each population.

PMID- 9140540
TI  - Recognition of leukemia in skeletal remains: report and comparison of two cases.
AB  - Recognition of disease in the archeologic record is facilitated by
      characterization of the skeletal impact of documented (in life) disease. The
      present study describes the osteological manifestations of leukemia as identified
      in the skeletons of two individuals diagnosed during life: a 3-year-old black
      girl with acute lymphocytic leukemia and a 60-year-old white male with acute
      myelogenous leukemia in the Hamann-Todd collection. Contrasting with the lack of
      specificity of radiologic findings, macroscopic skeletal changes appear
      sufficiently specific to allow distinguishing leukemia from other forms of
      cancer. While leukemia appears confidently diagnosable, distinguishing among the
      varieties (e.g., myelogenous and lymphocytic) does not appear possible at this
      time. Skeletal findings in leukemia are presented in tabular form to facilitate
      their application to future diagnosis of the disease in the archaeological
      record.

PMID- 9140541
TI  - Developmental age and taxonomic affinity of the Mojokerto child, Java, Indonesia.
AB  - An increasing number of claims place hominids outside Africa and deep in
      Southeast Asia at about the same time that Homo erectus first appears in Africa.
      The most complete of the early specimens is the partial child's calvaria from
      Mojokerto (Perning I), Java, Indonesia. Discovered in 1936, the child has been
      assigned to Australopithecus and multiple species of Homo, including H.
      modjokertensis, and given developmental ages ranging from 1-8 years. This study
      systematically assesses Mojokerto relative to modern human and fossil hominid
      growth series and relative to adult fossil hominids. Cranial base and vault
      comparisons between Mojokerto and H. sapiens sapiens (Hss) (n = 56), Neandertal
      (n = 4), and H. erectus (n = 4) juveniles suggest a developmental age range
      between 4 and 6 years. This range is based in part on new standards for assessing
      the relative development of the glenoid fossa. Regression analyses of vault arcs
      and chords indicate that H. erectus juveniles have more rounded frontals and less
      angulated occipitals than their adult counterparts, whereas Hss juveniles do not
      show these differences relative to adults. The growth of the cranial
      superstructures and face appear critical to creating differences in vault
      contours between H. erectus and Hss. In comparison with adult H. erectus and
      early Homo (n = 27) and adult Hss (n = 179), the Mojokerto child is best
      considered a juvenile H. erectus on the basis of synapomorphies of the cranial
      vault, particularly a metopic eminence and occipital torus, as well as a suite of
      characters that describe but do not define H. erectus, including obelion
      depression, supratoral gutter, postorbital constriction, mastoid fissure, lack of
      sphenoid contribution to glenoid fossa, and length and breadth ratios of the
      temporomandibular joint. Mojokerto is similar to other juvenile H. erectus in the
      degree of development of its cranial superstructures and its vault contours
      relative to adult Indonesian specimens. The synapomorphies which Mojokerto shares
      with H. erectus are often considered autapomorphies of Asian H. erectus and
      confirm the early establishment and long-term continuity of the Asian H. erectus
      bauplan. This continuity does not, however, necessarily reflect on the pattern of
      origin of modern humans in the region.

PMID- 9140542
TI  - Functional morphology of the postcranium and locomotor behavior of Neosaimiri
      fieldsi, a Saimiri-like Middle Miocene platyrrhine.
AB  - A number of postcranial specimens of Neosaimiri fieldsi, a Middle Miocene
      platyrrhine, were discovered in 1988, 1989, and 1990 at La Venta, Colombia. Until
      recently only three postcranial specimens of this species had been discovered and
      the present material adds further information about this taxon's postcranial
      morphology. In overall skeletal dimensions and in postcranial features,
      Neosaimiri is most similar to Saimiri among extant medium-sized platyrrhines, but
      differs from Saimiri in having more rugose surface markings, a longer olecranon,
      a smaller anterior process of the distal tibia, an absence of a distal surface
      extension on the anterior tibial shaft, an absence of an anterior midtrochlear
      depression of the talus, and a shorter distal calcaneus relative to the calcaneal
      tuberosity. These differences suggest that Neosaimiri was relatively heavily
      built, possessed a more dominant forelimb in quadrupedal progression, and
      utilized a less stabilized upper ankle joint, and a shorter power arm for
      plantarflexion. Neosaimiri is interpreted as an arboreal quadruped with frequent
      leaping across arboreal gaps, as in extant Saimiri, with perhaps less frequent
      running and leaping than in Saimiri. As with the dentition, the postcranial
      specimens suggest the close relationship between Neosaimiri and extant Saimiri.

PMID- 9140543
TI  - Cranial growth in Saimiri sciureus (Cebidae) and its alteration by nutritional
      factors: a longitudinal study.
AB  - Ten male Saimiri sciureus boliviensis (Cebidae), born at the Centro Argentino de
      Primates (CAPRIM), were grown in captivity. At weaning (6 months old), five
      individuals were fed ad libitum on a 20% protein diet (controls). The other five
      animals were fed ad libitum on a 5% protein diet (malnourished). Animals were
      radiographed monthly. The length, width, and height of the anterior, middle, and
      posterior components of the neurocranium, and those of the masticatory,
      respiratory, and optic components of the face were measured. A pattern of high
      growth rate was observed in both the three facial and the middle neural
      components. The anterior and posterior neural components showed a pattern of low
      rate of growth. The growth behavior of each variable was also different. Lengths
      grew more than widths and heights in the facial components, whereas widths grew
      more than heights and lengths in the neurocranium. Malnutrition delayed growth in
      size and altered the normal shape changes. High-patterned variables, such as
      masticatory and respiratory lengths, and the anterior and middle neural widths
      were particularly affected. The masticatory and the middle neural components
      underwent the greatest growth arrest. The optic and the respiratory components
      suffered a mild effect. The anterior and the posterior neural components were
      affected to a lesser degree.

PMID- 9140544
TI  - Sutural bone frequency in synostotic rabbit crania.
AB  - This study tests the hypothesis that crania with synostosed sutures will have a
      significantly higher incidence of calvarial sutural bones than normal crania.
      Sutural bones were counted in seven calvarial sutures and compared among four
      groups of adult New Zealand white rabbit skulls: normal in-colony (NI) controls
      (N = 14), normal out-colony (NO) controls (N = 12), skulls with familial delayed
      onset (DO) coronal synostosis (N = 25), and skulls with experimentally
      immobilized coronal sutures (EI) (N = 20). Comparisons among groups were made
      with a Kruskal-Wallis one-way ANOVA and between groups with a Mann-Whitney U
      test, using a Bonferroni correction for multiple comparisons. Significant
      differences (P < 0.05) were noted only in the coronal and sagittal sutures, with
      EI crania having the greatest number of coronal sutural bones; between group
      differences were undetectable for sagittal sutural bones. A post hoc two-sample
      binomial test for equal proportions showed that the distribution of coronal
      sutural bones among individuals across groups was even, while the distribution of
      sagittal sutural bones was significantly higher in EI crania. These results
      suggest that altered sutural forces of the calvaria contribute to an increased
      occurrence of sutural bones. However, the influence of inheritance on increased
      occurrence of sutural bones cannot be discounted, as reflected in the equivalent
      number of individuals across groups that possessed coronal sutural bones.

PMID- 9140545
TI  - Brief communication: evidence of pathology on the frontal bone from Gongwangling.
AB  - The hominid fossil from Gongwangling (Lantian) is well known and described (Woo,
      [1965] Scientia Sinca 14:1032-1036; Woo [1966] Curr. Anthropol. 7:83-86; Wu and
      Dong [1985] in R Wu and JW Olsen (eds.): Palaeoanthropology and Paleolithic
      Archaeology in the People's Republic of China [New York: Academic Press, pp. 79
      89]; Wu and Poirier [1995] Human Evolution in China: A Metric Description of the
      Fossils and a Review of the Sites [Oxford: Oxford University Press]). However,
      evidence of pathology on the frontal bone has been previously unreported. Two
      lesions occur on the right supraorbital region that can be distinguished from
      marks of erosion prevalent on this specimen. These are discrete and irregularly
      shaped, with evidence of secondary bone formation surrounding them. The cause of
      the condition is unclear. Possibilities include trauma or abscess from an
      unspecified infection.

PMID- 9140546
TI  - Brief communication: estimates of some demographic parameters in a Neolithic rock
      cut chamber (approximately 2000 BC) using iterative techniques for aging and
      demographic estimators.
AB  - Two new techniques-one anthropological, which estimates the mean age at death for
      adult skeletons, the other demographic, which gives main survivorship curve
      parameters-are used on a sample of skeletons (N approximately 170) discovered in
      a Neolithic rock-cut chamber (Loisy-en-Brie, France). The iterative technique for
      aging used a stochastic sampled F matrix derived from the trabecular involution
      of the femoral head observed in the reference collection of Coimbra (Portugal; N
      = 421). The results, obtained from techniques and data, independent of each
      other, are strongly consistent. Overall, they give a life expectancy at birth of
      about 25-28 years and the probability of death at 1 and 5 years, respectively, of
      about .271-.249 and .429-.380.

PMID- 9140547
TI  - Clone sheds light on research, ethical questions.

PMID- 9140549
TI  - Cerebrospinal fluid gamma-aminobutyric acid and glutamate values in dogs with
      epilepsy.
AB  - OBJECTIVES: To investigate changes in CSF concentrations of inhibitory and
      excitatory neurotransmitters in dogs with confirmed idiopathic epilepsy, and to
      evaluate them with regard to the clinical characteristics of the sample
      population and of the seizures. ANIMALS: 13 (8 male and 5 female) drug-naive dogs
      with an initial generalized seizure, 6 (4 male and 2 female) drug-naive dogs with
      an initial partial seizure, and 10 clinically normal (5 male and 5 female)
      control dogs. PROCEDURE: At least 24 hours after the last observed seizure, CSF
      was collected aseptically from the cisterna cerebellomedullaris, and a portion
      was immediately aliquoted into vials, placed on dry ice, then stored at -80 C.
      The CSF glutamate (GLU) and gamma-aminobutyric acid (GABA) concentrations were
      estimated by use of HPLC with electrochemical detection. Cerebellomedullary
      cisternal CSF glutamate and GABA values were analyzed in dogs with noninduced
      idiopathic epilepsy. Comparisons were determined for differences attributable to
      weight, sex, age at first seizure, seizure type, and total time of past seizure
      history. RESULTS: Mean (range) age at onset of the first seizure was 3.33 (0.1 to
      11), 3.5 (0.1 to 11), and 3.25 (0.5 to 9) years for all dogs, dogs with initial
      partial seizure, and dogs with initial generalized seizure, respectively. Low
      GABA and high GLU values were found in the CSF of epileptic dogs, and were
      independent of time elapsed between the first observed seizure and CSF sample
      collection. The GABA value was inversely related to body weight in epileptic
      dogs, independent of age. Changes in GABA and GLU concentrations were not related
      to seizure type. CONCLUSIONS: Altered GABA and GLU values in CSF might be
      indicative of a state of chronic overexcitation in the brain of dogs with primary
      or idiopathic epilepsy. CLINICAL RELEVANCE: CSF GABA and GLU may serve as
      important markers in epileptic dogs for potential response to antiepileptic
      drugs.

PMID- 9140548
TI  - Effects of three sedative protocols on glomerular filtration rate in clinically
      normal dogs.
AB  - OBJECTIVE: To determine the effects of 3 sedative protocols (butorphanol and
      diazepam [BD] IV; acepromazine and butorphanol [AB] IV; diazepam and ketamine
      [DK] IV) on glomerular filtration rate (GFR) as measured by 99mTc DTPA nuclear
      scintigraphy and to compare them with GFR measured without sedation.
      Cardiovascular, respiratory, and sedative effects of each protocol also were
      measured. ANIMALS: 12 adult male Walker Hounds. PROCEDURE: Systolic, diastolic,
      and mean arterial blood pressures and heart and respiratory rates were measured
      before, during, and after scintigraphic measurement of GFR. RESULTS: Difference
      in GFR was not significant between any of the sedative regimens and the control.
      The DK protocol caused significant increases in systolic, diastolic, and mean
      arterial blood pressure; compared with the AB and BD protocols, it caused
      significant increases in heart rate versus all protocols, and was associated with
      the lowest mean GFR (2.80 ml/min/kg of body weight). The AB protocol caused
      significant decreases in systolic, diastolic, and mean arterial blood pressures,
      compared with DK and the nonsedation protocols. Mean GFR for the BD protocol was
      2.94 ml/min/kg, and was 3.13 ml/min/kg for the AB and the nonsedation protocols.
      The AB protocol provided the best sedation with minimal additional restraint
      required. The BD and nonsedation protocols often were associated with substantial
      dog movement. The DK protocol induced inadequate duration of immobilization (< 10
      minutes) in some dogs and excitement in others. CONCLUSION: GFR measurements
      obtained with any of the sedative protocols were not significantly different,
      compared with measurements in awake dogs. The AB protocol provides the best
      sedative effects and was associated with GFR values identical to those in awake
      dogs. Systemic hypotension caused by acepromazine did not decrease GFR in
      clinically normal dogs.

PMID- 9140550
TI  - Evaluation of arginine-glycine-aspartate-containing peptides as inhibitors of
      equine platelet function.
AB  - OBJECTIVES: To determine whether synthetic peptides containing the arginine
      glycine-aspartate (RGD) sequence inhibit equine platelet function. ANIMALS: For
      in vitro studies of blood, 3 healthy Thoroughbreds; for in vivo and ex vivo
      studies of administration of RGD-containing peptides, 4 young adult pony mares.
      PROCEDURE: Blood was incubated with and without addition of aspirin or RGD
      containing peptides (RGDS, RPR 110885) and platelet aggregation responses and
      platelet adhesion to subendothelial collagen were determined. RPR 110885 was
      administered IV, and platelet function was evaluated. Platelet aggregation was
      determined by a turbidimetric method, and platelet adhesion was evaluated by the
      Baumgartner perfusion method. RPR 110885 was administered IV at dosages of 30 and
      60 micrograms/kg of body weight, and bleeding time, platelet aggregation
      responses, and platelet count were determined at hourly intervals for 4 hours.
      RESULTS: Both RGDS and RPR 110885 inhibited platelet aggregation in vitro in dose
      dependent manner and inhibited platelet adhesion to subendothelial collagen. The
      concentration of RGDS that inhibited platelet aggregation by 50% (IC50) was 100
      to 142 microM for the various agonists tested, whereas the concentration of RPR
      110885 that inhibited platelet aggregation by 50% was 0.03 to 0.05 microM. When
      administered to ponies at 30 or 60 g/kg, RPR 110885 almost completely inhibited
      ADP-induced platelet aggregation. CONCLUSIONS: RGDS and RPR 110885 inhibited
      equine platelet function; however, RPR 110885 was several thousand times more
      potent than RGDS. CLINICAL RELEVANCE: RGD-containing peptides may be useful for
      treatment of thrombotic diseases of horses.

PMID- 9140551
TI  - Structural, material, and anatomic characteristics of the collateral ligaments of
      the canine cubital joint.
AB  - OBJECTIVE: To document gross and microscopic anatomic features of the collateral
      ligaments of the canine cubital joint and to determine their structural and
      material properties. ANIMALS: 37 canine cadavers. PROCEDURE: After measurement of
      ligament dimensions, the bone-collateral ligament-bone specimens were loaded in
      tension until failure, using a materials testing machine. Data from the load
      displacement curves were used to determine the structural and material properties
      of the ligaments. Gross anatomic features were studied during dissection of the
      specimens from the medial collateral ligament (MCL) and lateral collateral
      ligament (LCL), which then were saved for microscopic examination. RESULTS:
      Failure load and stiffness values for the LCL were significantly (P < 0.05)
      greater than those for the MCL. The LCL had obvious cranial and caudal components
      that attached to the radius and ulna, respectively. The MCL also had cranial and
      caudal components; however, the cranial component was indistinct, appearing only
      as a slight thickening of the joint capsule. The caudal component was more
      prominent; as it extended distad, it had minor attachments to the interosseous
      and annular ligaments and attached principally on the caudolateral surface of the
      proximal portion of the radius. The caudal component did not have substantial
      attachment to the ulna in any of the specimens studied. Both ligaments were
      composed of closely packed, parallel fascicles of dense collagen, with scant
      amounts of fibrocartilage and no detectable elastin. CONCLUSIONS: Gross anatomic
      features of the collateral ligaments of the canine cubital joint indicate that
      they provide principal structural support to the joint; microscopic anatomic
      features are typical of other ligaments. The LCL is stronger and stiffer than the
      MCL; however, their material properties are similar. CLINICAL RELEVANCE:
      Knowledge of the sites of attachment of collateral ligament components is
      essential for surgeons undertaking repair or reconstruction of these structures.

PMID- 9140552
TI  - Epidemiologic evaluation of the risk factors associated with exposure and
      seroreactivity to Bartonella vinsonii in dogs.
AB  - OBJECTIVES: To determine seroprevalence to Bartonella vinsonii subsp berkhoffii
      in a population of sick dogs from North Carolina and Virginia and to evaluate
      potential risk factors associated with increased likelihood of exposure to the
      organism. SAMPLE POPULATION: Serum samples from 1,920 sick dogs. PROCEDURE: An
      indirect fluorescent antibody assay was performed on each sample, and the end
      point antibody titer was recorded. A case (seropositive) was defined as a dog
      with reciprocal titer > or = 64, and a control (seronegative) was defined as a
      dog with reciprocal titer < 16 that was referred within 0 to 3 days of referral
      of a corresponding case. From this population, 207 dogs (69 cases and 138
      controls) were included in a case-control seroepidemiologic study. RESULTS: 3.6%
      (69/1,920) of the dogs were seropositive to B vinsonii subsp berkhoffii. Results
      of the case-control study indicated that seropositive dogs were more likely to
      live in rural environments, frequently on a farm, were free to roam the
      neighborhood, and were considered to be predominantly outdoor dogs. Moreover,
      seropositive dogs were 14 times more likely to have a history of heavy tick
      exposure. After analysis of the case-control study, a more detailed examination
      of banked sera from dogs with known tick exposure was performed. High correlation
      was found between sero-reactivity to B vinsonii and seroreactivity to E canis or
      B canis (36.0 and 57.1%, respectively). Sera derived from dogs experimentally
      infected with E canis or R rickettsii did not cross react with B vinsonii
      antigen. CONCLUSIONS AND CLINICAL RELEVANCE: Several potential risk factors are
      associated with canine exposure to B vinsonii. Rhipicephalus sanguineus, the tick
      vector for E canis and B canis, may be involved in B vinsonii transmission among
      dogs.

PMID- 9140553
TI  - Safety and immunogenicity of Brucella abortus strain RB51 vaccine in pregnant
      cattle.
AB  - OBJECTIVE: To determine the safety and immunogenicity of Brucella abortus strain
      RB51 as a vaccine in pregnant cattle. ANIMALS: 12 Polled Hereford heifers
      obtained from a brucellosis-free herd and bred on site at 16 months of age to a
      brucellosis-free bull. PROCEDURE: Pregnant heifers were vaccinated at 6 months'
      gestation with 10(9) colony-forming units of B abortus strain RB51 (n = 5), 3 x
      10(8) colony-forming units of B abortus strain 19 (n = 5), or sterile pyrogenfree
      saline solution (n = 2). Samples were periodically collected for serologic
      testing and lymphocyte blastogenesis assays. At full gestation, heifers were
      euthanatized and specimens were collected for bacteriologic culture, histologic
      analysis, and lymphocyte blastogenesis assay, using various antigenic stimuli.
      RESULTS: None of the strain RB51- or strain 19-vaccinates aborted or had gross or
      microscopic lesions at necropsy that were consistent with brucellosis. Maternal
      blood mononuclear cells from strain RB51- and strain 19-vaccinates had
      proliferative responses to gamma-irradiated strain RB51 and strain 19 that were
      greater than responses by cells from nonvaccinated controls. In contrast,
      maternal superficial cervical lymph node cells from strain 19-vaccinates had
      proliferative responses to gamma-irradiated strain RB51 or strain 19 bacteria
      greater than those of cells from RB51-vaccinates and nonvaccinated controls. None
      of the heifers vaccinated with strain RB51 developed antibodies detected by use
      of the standard tube agglutination test, but all developed antibodies to strain
      RB51 that reacted in a dot ELISA, using irradiated strain RB51 as antigen.
      CONCLUSIONS: Pregnant cattle can be safely vaccinated with strain RB51 without
      subsequent abortion or placentitis. Furthermore, strain RB51 is immunogenic in
      pregnant cattle, resulting in humoral and cell-mediated immune responses, but
      does not interfere with serologic diagnosis of field infections.

PMID- 9140554
TI  - Phosphoprotein profile analysis of ruminant respiratory syncytial virus isolates.
AB  - OBJECTIVE: To determine the apparent molecular weight for 24 ruminant respiratory
      syncytial viruses (RSV) on the basis of differences in the electrophoretic
      mobility of the phosphoprotein (P protein). PROCEDURE: 29 bovine RSV (BRSV), 20
      of which were not previously tested, 3 ovine RSV, and 1 caprine RSV isolates were
      selected for determination of electrophoretic mobility of the P protein. Virus
      radiolabeled with [35S]methionine was immunoprecipitated with polyclonal
      antiserum to BRSV and analyzed by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. RESULTS: On the basis of apparent molecular size of the P
      protein, all isolates could be categorized into 2 electropherotypes, low
      molecular size of 36 kd and high molecular size of 38 kd. Twenty-three BRSV, the
      3 ovine RSV, and 1 caprine RSV isolates had a high molecular size P protein; 6
      BRSV isolates had a low molecular size P protein. CONCLUSIONS: The apparent
      molecular size of the P protein of the ruminant RSV strains is greater than that
      of the human RSV subgroups, providing further evidence of their distinctiveness.
      Whether categorization of electrophoretic mobility of the P protein of BRSV
      underlies distinct antigenic subgroups, as it does in human RSV, requires further
      antigenic and genetic analysis. CLINICAL RELEVANCE: Antigenic subgroups of
      ruminant RSV may have relevance in the development of new vaccines for control of
      the disease.

PMID- 9140555
TI  - Diversity of Streptococcus agalactiae and Staphylococcus aureus ribotypes
      recovered from New York dairy herds.
AB  - OBJECTIVES: To develop a reference database for characterization of bovine
      Staphylococcus aureus and Streptococcus agalactiae strains by automated
      ribotyping and to use it to assess the discriminatory power of this typing
      procedure and the geographic distribution of Sta aureus and Str agalactiae
      strains in New York state dairy herds. SAMPLE POPULATION: 22 commercial dairy
      herds. PROCEDURE: Isolates of Sta aureus and Str agalactiae from bovine milk were
      identified by standard bacteriologic procedures, then typed by automated
      ribotyping. Antimicrobial susceptibility of isolates was tested in vitro. Two
      indicators made from the data were percentage of farms with multiple ribotypes
      and percentage of single ribotypes found in several geographic regions. Standard
      bacteriologic diagnosis, automated ribotyping, and determination of antibiograms
      (Kirby-Bauer method) also were done. RESULTS: Of 50 Sta aureus and 44 Str
      agalactiae isolates from composite milk samples of 12 and 10 herds, respectively,
      18 and 14 ribotypes, respectively, were identified. The discriminatory power of
      automated ribotyping was approximately 0.96 (Hunter-Gaston's formula). A higher
      percentage of herds with Sta aureus had multiple ribotypes. The most common Sta
      aureus ribotypes tended to have broader geographic distribution. Some Sta aureus
      ribotypes were significantly associated with antibiotic resistance profiles.
      CONCLUSIONS: Automated ribotyping appears to characterize bovine strains of
      bacteria associated with intramammary infections with a high discriminatory
      index. Potential applications include identification of strains that appear to
      have broad geographic distribution suggesting interfarm transfer, discrimination
      between recurrent versus new intramammary infections (ie, for control of Str
      agalactiae and Sta aureus), and evaluation of antibiotic therapy.

PMID- 9140556
TI  - Effect of heparin on infection of cells by porcine reproductive and respiratory
      syndrome virus.
AB  - OBJECTIVE: To investigate whether heparin has any effect on the growth of porcine
      reproductive and respiratory syndrome virus (PRRSV). SAMPLE POPULATION: 2
      isolates of PRRSV, and as control viruses, 1 isolate of pseudorabies virus (PRV)
      and 1 isolate of parainfluenza 3 virus (PIV-3). PROCEDURES: Plaque assays, using
      a continuous cell line (MARC-145) derived from African green monkey kidney cell
      line (MA104), were performed for determination of inhibitory effect of heparin on
      PRRSV, PRV, and PIV-3. The effect of various doses of heparin and heparinase on
      the growth of PRRSV, PRV, and PIV-3 was evaluated and compared. In each
      experiment, value were expressed as the mean value for duplicate samples.
      RESULTS: The number of plaques formed by PRRSV and PRV was reduced to 24 to 25
      and 15% of the untreated control (100%), respectively, by 1 U of heparin/ml, but
      could not be reduced below 6 to 7 and 3%, respectively, by use of concentrations
      up to 50 U/ml. An inhibitory effect of heparin, at a concentration up to 50 U/ml,
      was not observed on PIV-3. Delaying addition of heparin for 30 minutes after the
      addition of PRRSV and PRV reduced plaque formation by 48 to 51 and 68%,
      respectively, compared with 91 to 92 and 95%, respectively, if heparin was added
      at the time of infection. In addition, most PRRSV added was retained by heparin
      beads, as was PRV. Heparinase treatment of MARC-145 cells reduced the number of
      PRRSV-, as well as PRV-induced plaques. On the other hand, the number of PIV-3
      induced plaques did not decrease after treatment of MARC-145 cells with
      heparinase. CONCLUSIONS: Addition of heparin to PRRSV or to the MARC-145 cells
      before virus inoculation and treatment of the cells with heparinase prevented the
      virus from infecting the cells.

PMID- 9140557
TI  - Relapsing bacteremia after blood transmission of Bartonella henselae to cats.
AB  - OBJECTIVES: To determine persistence of bacteremia, pathogenicity, and
      immunoglobulin kinetics after blood transmission of Bartonella henselae in cats.
      ANIMALS: 18 specific-pathogen-free (SPF) cats (16 weeks old) received blood or
      urine from 4 adult cats (2 SPF, 2 naturally infected with B henselae). PROCEDURE:
      SPF cats were inoculated with blood IV (n = 4), blood IM (n = 4), or urine
      sediment IM (n = 4) from 2 bacteremic cats (donors A and B). Control cats
      (2/route) received inoculum from culture-negative, seronegative SPF cats (donors
      C and D). RESULTS: 6 cats (5 blood, 1 urine) were transiently febrile during the
      213-day observation period. Two bacteremic cats developed CNS abnormalities.
      Transient anemia was the only hematologic abnormality. Bacteremia was induced in
      7 of 8 blood recipients by postinoculation day (PID) 11. Urine recipients (n = 6)
      did not become bacteremic or seroconvert by PID 108, but when challenge exposed
      IV with blood, 4 of 6 became infected. All infected cats developed relapsing
      bacteremia. Initially, colony counts for donor-A recipients were 10(3) greater
      than those for donor-B recipients; however, during relapses, counts were similar.
      Polymerase chain reaction-restriction fragment length polymorphism analysis of
      16S rRNA gene and the intergenic spacer region revealed no differences among
      isolates derived from recipient cats. Bartonella henselae-specific antibodies
      were detected between PID 15 and 18 in donor-A, compared with PID 46 and 181 in
      donor-B recipients. The peak geometric mean titer of donor-A recipients was
      1,448, versus 406 for donor-B recipients. CONCLUSIONS AND CLINICAL RELEVANCE:
      Blood transmission of B henselae induced subtle clinical abnormalities; the
      biological behavior of the 2 donor strains differed; and relapsing bacteremia can
      persist in conjunction with variably high antibody titers.

PMID- 9140558
TI  - In vitro effects of an acidic by-product feed on bovine teeth.
AB  - OBJECTIVE: To evaluate in vitro erosive effects of sweet potato cannery waste
      (SPCW) on bovine incisor enamel. SAMPLE POPULATION: 20 bovine mandibles.
      PROCEDURE: Mandibles were collected and incisors were classified into 3
      categories: lacking observable wear, advanced normal wear, or abnormal wear
      associated with feeding SPCW. Intact mandibles were radiographed. Contralateral
      normal teeth from the same jaw were used to compare Ca2+ loss (etching) with
      SPCW, lactic acid (pH 3.2), or SPCW neutralized with NaOH to pH 5.0 or 5.5.
      Scanning electron microscopy was performed to compare etched and unetched
      specimens. Two abnormally worn teeth were evaluated histologically. Knoop
      hardness testing was conducted on unexposed areas of surface enamel and enamel
      exposed to SPCW. RESULTS: Radiography revealed large periapical abscesses in the
      mandibles exposed to SPCW. Nearly identical amounts of Ca2+ were removed by SPCW
      and lactic acid solution at the same pH. Scanning electron microscopy did not
      indicate consistent differences between etch patterns resulting from exposure to
      SPCW or lactic acid. Mean rate of calcium removal was 56% higher in deciduous
      than permanent teeth. Knoop hardness data suggested that softening occurred in
      enamel exposed to SPCW. Neutralizing SPCW to pH 5.5 eliminated calcium removal.
      Histologic examination of sections indicated that SPCW degraded and removed some
      dentin matrix proteins. CONCLUSIONS: Exposure to SPCW results in enamel erosion
      in vitro; low pH is the most likely cause of erosion. Neutralizing SPCW to pH 5.5
      eliminated erosive effects. CLINICAL RELEVANCE: Confirmation of SPCW's erosive
      effects on enamel in vitro supported the field diagnosis.

PMID- 9140559
TI  - Bioavailability and pharmacokinetics of intravenously and orally administered
      allopurinol in healthy beagles.
AB  - OBJECTIVES: To determine bioavailability and pharmacokinetic parameters for
      allopurinol and its active metabolite, oxypurinol. ANIMALS: 6 healthy,
      reproductively intact female Beagles, 4.9 to 5.2 years old, and weighing 9.5 to
      11.5 kg. PROCEDURE: In the first part of the study, allopurinol was administered
      IV at a dosage of 10 mg/kg of body weight to 3 dogs and 5 mg/kg to 3 dogs; the
      sequence was then reversed. In the second part of the study, allopurinol was
      administered orally at a dosage of 15 mg/kg to 3 dogs and 7.5 mg/kg to 3 dogs;
      the sequence was then reversed. In the third part of the study, allopurinol was
      administered IV (10 mg/kg), orally (15 mg/kg) with food, and orally (15 mg/kg)
      without food. Plasma samples were obtained at timed intervals, and concentrations
      of allopurinol and oxypurinol were determined. RESULTS: Maximal plasma
      allopurinol concentration and area under plasma allopurinol and oxypurinol
      concentration-time curves were 2 times greater when dogs were given 10 mg of
      allopurinol/kg IV, compared with 5 mg/kg, and when dogs were given 15 mg of
      allopurinol/kg orally, compared with 7.5 mg/kg. Allopurinol elimination half
      life, time to reach maximal plasma oxypurinol concentration, and oxypurinol
      elimination half-life were significantly greater when dogs received 10 mg of
      allopurinol/kg IV, compared with 5 mg/kg, and when dogs received 15 mg of
      allopurinol/kg orally, compared with 7.5 mg/kg. CONCLUSIONS: Elimination of
      allopurinol is dependent on nonlinear enzyme kinetics. The bioavailability of
      allopurinol, and pharmacokinetic parameters of allopurinol and oxypurinol after
      oral administration of allopurinol, are not affected by administration with food.
      CLINICAL RELEVANCE: A dose threshold exists beyond which additional allopurinol
      would not substantially further inhibit xanthine oxidase activity. Oral
      administration of > 15 mg of allopurinol/kg to dogs would not be expected to
      result in greater reduction of plasma and urine uric acid concentrations. Also,
      allopurinol may be administered to dogs for dissolution or prevention of urate
      uroliths without regard to time of feeding.

PMID- 9140560
TI  - Influence of two diets on pharmacokinetic parameters of allopurinol and
      oxypurinol in healthy beagles.
AB  - OBJECTIVES: To determine whether diet influences the metabolism of IV
      administered allopurinol in healthy dogs. ANIMALS: 6 healthy female Beagles, 4.9
      to 5.2 years old and weighing 9.6 to 11.5 kg. PROCEDURES: Allopurinol was
      administered IV (10 mg/kg) while dogs consumed a 10.4% protein (dry weight),
      casein-based diet or a 31.4% (dry weight), meat-based diet. After each dose,
      plasma samples were obtained at timed intervals, and concentrations of
      allopurinol and its active metabolite, oxypurinol, were determined by high
      performance liquid chromatography. An iterative, nonlinear regression analytical
      program was used to determine the weighted least-squares, best-fit curves for
      plasma allopurinol and oxypurinol concentration-time data. From these data,
      pharmacokinetic parameters were calculated. RESULTS: Pharmacokinetic parameters
      for allopurinol and oxypurinol were not different when comparing the effect of
      diet. CONCLUSION: There is no influence of diet on pharmacokinetic parameters of
      allopurinol or oxypurinol. CLINICAL RELEVANCE: In contrast to observations in
      human beings, allopurinol metabolism is not influenced by diet. Therefore,
      formation of xanthine-containing calculi in dogs consuming a high-protein diet
      and receiving allopurinol is probably not attributable to alteration of
      allopurinol metabolism.

PMID- 9140561
TI  - Temporal effects of an infusion of dopexamine hydrochloride in horses
      anesthetized with halothane.
AB  - OBJECTIVE: To evaluate the hemodynamic effects of a 60-minute infusion of
      dopexamine in horses anesthetized with halothane. ANIMALS: 7 adult Thoroughbreds.
      PROCEDURE: Measurements of left ventricular function obtained by transesophageal
      Doppler echocardiography and cardiac catheterization. RESULTS: Infusion of
      dopexamine (4 micrograms/kg of body weight/min) significantly increased heart
      rate, cardiac output, maximal rates of increase and decrease of left ventricular
      pressure, and maximal acceleration and maximal velocity of aortic blood flow.
      Left ventricular ejection time significantly increased, and pre-ejection period
      decreased during the infusion. Cardiac output, maximal rate of increase of left
      ventricular pressure, and maximal acceleration continued to increase as the
      infusion progressed. Right ventricular end-diastolic pressure was significantly
      decreased after 20 minutes of infusion and decreased progressively throughout the
      remaining time of infusion. Many hemodynamic variables, including right
      ventricular end-diastolic pressure, had not returned to control values 30 minutes
      after the infusion was discontinued. A number of undesirable adverse effects were
      observed in horses receiving dopexamine infusion; during administration, profuse
      sweating occurred in every horse. In 6 horses, recovery from anesthesia was
      associated with excitement and violent shivering. Colic developed in 2 horses
      within 3 hours of recovery. CONCLUSIONS: Dopexamine (4 micrograms/kg/min) does
      not achieve a peak effect on many hemodynamic variables within a short period of
      commencing administration, and the effects of infusion may persist for extended
      periods after drug administration is discontinued. CLINICAL RELEVANCE: Dopexamine
      has a hemodynamic profile suited to treatment of low cardiac output in
      anesthetized horses; however, at the dosage rate studied (4 micrograms/kg/min),
      its administration was associated with a number of undesirable adverse effects
      which could preclude its clinical use.

PMID- 9140562
TI  - Insulin-like growth factor 1 and corticosteroid modulation of chondrocyte
      metabolic and mitogenic activities in interleukin 1-conditioned equine cartilage.
AB  - OBJECTIVE: To evaluate potential stimulatory or matrix-sparing effects of insulin
      like growth factor 1 (IGF-1), alone or in combination with a corticosteroid, in
      an interleukin 1 (IL-1)-induced model of cartilage degradation. SAMPLES:
      Cartilage from the weightbearing surfaces of trochlea and condyles of clinically
      normal 2-year-old male horses. PROCEDURE: Triamcinolone acetonide and IGF-1
      effects were evaluated by assessing: matrix responses by sulfated
      glycosaminoglycan (GAG) assay and [35S]sulfated GAG synthesis; collagen content
      by hydroxyproline assay; and mitogenic response by [3H]thymidine incorporation
      into DNA and fluorometric assay of total DNA concentration. RESULTS: Conditioning
      of cartilage explants with 10 ng of human recombinant IL-1 alpha increased
      degradation and decreased synthesis of matrix proteoglycans (PG), without
      affecting matrix collagen content. Human recombinant IGF-1 decreased PG loss and
      reversed the reduction of PG synthesis in cartilage explants conditioned with IL
      1. Given alone, steroids decreased PG concentration and synthetic rate in normal
      cartilage. However, the previously diminished PG content, attributable to IL-1
      conditioning, was not further exacerbated by steroid administration in IL-1
      conditioned explants. Combined treatment of normal cartilage explants with IGF-1
      and steroids resulted in PG preservation and increase in collagen content.
      Similar PG and collagen effects were not evident when treating IL-1-conditioned
      cartilage with IGF-1/steroid combinations. Decrease in chondrocyte proliferation
      was associated with steroid administration. Exposure to IGF and steroids
      prevented the decrease in mitogenesis that could lead to cellular loss,
      particularly in IL-1-conditioned explants. CONCLUSION: Combination IGF-1 and
      steroid treatment of normal cartilage cultures indicated substantial ability to
      override the anabolic suppression associated with steroids alone. Potentially,
      administration of corticosteroids, followed by IGF-1, may act to decrease
      propagation of detrimental mediator release while allowing appreciation of the
      chondroenhancing effects of IGF-1. These beneficial effects were considerably
      reduced in IL-1-induced cartilage damage.

PMID- 9140563
TI  - Effect of transportation on the composition of bronchoalveolar lavage fluid
      obtained from horses.
AB  - OBJECTIVE: To study the effects of extended transportation on the composition of
      bronchoalveolar lavage fluid (BALF) obtained from horses. ANIMALS: 30 horses (14
      males, 16 females: 25 Thoroughbreds and 5 Thoroughbred-Arabian cross-breds; 27 to
      30 months old) without a history or clinical signs of respiratory tract disease.
      Bronchoalveolar lavage was performed on nontransported control horses (groups 1
      and 2) and transported horses (group 3). PROCEDURE: 20 horses were used to
      determine the effect of 41 hours of transportation on the composition of BALF
      (group 3). Bronchoalveolar lavage fluid was analyzed for recovered volume, number
      and distribution of nucleated cells, total protein and phospholipid
      concentrations, and phospholipid composition. RESULTS: Total number of nucleated
      cells in BALF from group-3 horses increased by approximately four-fold after
      transportation. Total protein concentration in BALF from group-3 horses also
      increased by approximately fivefold after transportation. Total phosphorus
      concentrations in group-3 horses decreased significantly from time 0 to
      immediately after transportation. In group-3 horses, the most characteristic
      change in composition of BALF after transport was a significant decrease in the
      concentration of phosphatidylglycerol. CONCLUSION AND CLINICAL RELEVANCE: The
      decrease in phosphatidylglycerol concentration in BALF after transportation
      indicates a reduction in the quantity of surfactant. This change may reflect
      either a decreased production of surfactant by alveolar type II epithelial cells
      or an increased removal of surfactant from the alveolar region. It is likely that
      extended transportation resulted in a decreased concentration of surfactant in
      BALF. Such a decrease may reduce the pulmonary defence mechanisms in the alveolar
      region, possibly resulting in infection.

PMID- 9140564
TI  - Plasma renin activity and angiotensin I and aldosterone concentrations in cats
      with hypertension associated with chronic renal disease.
AB  - OBJECTIVE: To determine plasma renin activity (PRA), angiotensin I (Ang I), and
      aldosterone (ALDO) values in clinically normal cats and hypertensive cats with
      renal disease, and the relation of renin-angiotensin-aldosterone activation in
      response to treatment with beta-blockers or angiotensin-converting enzyme
      inhibitors. ANIMALS: 5 normotensive healthy control cats and 12 Untreated
      hypertensive cats with chronic renal disease. PROCEDURE: Untreated hypertensive
      cats received either propanolol (n = 6) or enalapril (n = 6) as initial
      antihypertensive treatment. PRA and baseline plasma Ang I and ALDO concentrations
      were measured prior to treatment. The difference in Ang I values at 2 hours (Ang
      I generated) and at time 0 (baseline Ang I) was divided by 2 to give the PRA
      value. Values for PRA, Ang I, and ALDO were obtained from 5 clinically normal,
      normotensive cats, and compared with those of hypertensive cats. RESULTS: Mean +/
      SD PRA and baseline Ang I concentration were not significantly different between
      normotensive and hypertensive cats. Mean ALDO concentration was significantly (P
      = 0.0235) higher in hypertensive cats with renal disease (186.18 +/- 145.15
      pg/ml), compared with that in normotensive controls (51.1 +/- 16.76 pg/ml). Eight
      hypertensive cats with ALDO concentration > 2 SD above the mean concentration in
      control cats had low (n = 3), normal (n = 4), or high (n = 1) PRA, suggesting
      variable activation of the renin-angiotensin-aldosterone axis in the hypertensive
      state. Overall, enalapril was effective long-term monotherapy in only 1 of 6
      cats, and propranolol was ineffective as long-term monotherapy. CLINICAL
      RELEVANCE: Evaluation of the renin-angiotensin-aldosterone system in cats with
      hypertension associated with renal disease may lead to greater understanding of
      the pathophysiologic mechanisms of this disorder. In addition, identification of
      biochemical markers in hypertensive cats may permit selection of appropriate
      antihypertensive drugs. Propranolol and enalapril were ineffective
      antihypertensive agents in most cats of this study.

PMID- 9140565
TI  - Oncotic, hemodilutional, and hemostatic effects of isotonic saline and
      hydroxyethyl starch solutions in clinically normal ponies.
AB  - OBJECTIVE: To evaluate the oncotic, hemodilutional, and hemostatic effects of IV
      infusions of a large volume of isotonic saline solution and 2 doses of 6%
      hydroxyethyl starch (HES) in clinically normal ponies. ANIMALS: 12 adult ponies.
      PROCEDURE: Ponies were assigned to 3 treatment groups and received the following
      IV infusions: 80 ml of 0.9% sodium chloride/kg; 10 ml of 6% HES (in 0.9% sodium
      chloride)/kg; or 20 ml of 6% HES (in 0.9% sodium chloride)/kg. Blood samples were
      collected for determination of colloid oncotic pressure (COP), PCV, plasma total
      protein concentration, platelet count, von Willebrand factor antigen (vWf:Ag)
      activity, fibrinogen concentration, prothrombin time, activated partial
      thromboplastin time (APTT), and factor VIII coagulant (FVIII:C) activity. A
      rocket immunoelectrophoretic procedure was used for determination of vWf:Ag
      activity. A modification of the APTT assay was used for determination of FVIII:C
      activity. Cutaneous bleeding time was determined, using a template method.
      RESULTS: Mean COP was persistently increased over baseline values in the face of
      hemodilution in HES-treated ponies. Prothrombin time, APTT, and fibrinogen
      concentrations decreased after infusions and vWf:Ag and FVIII:C activities were
      decreased in dose-dependent manner in HES-treated ponies. Though cutaneous
      bleeding time was not significantly affected in ponies of any group, a trend
      toward prolongation of bleeding time was evident in ponies receiving 20 ml of
      HES/kg. This trend appeared to be associated with marked decrement in vWf:Ag
      activity at this dosage. CONCLUSIONS AND CLINICAL RELEVANCE: Infusion of HES in
      clinically normal ponies increases COP, and exerts dose-dependent hemodilutional
      effects and dose-dependent effects on specific hemostatic variables. Thus, HES
      may be useful for resuscitative fluid treatment of horses.

PMID- 9140566
TI  - Acute effects of intravenously administered hypertonic saline solution on
      transruminal rehydration in dairy cows.
AB  - OBJECTIVE: To determine the effect of IV administered hypertonic saline solution
      (HSS) on transruminal rehydration in clinically normal dairy cows. ANIMALS: 10
      Holstein cows. PROCEDURE: Cows in a 2-way randomized cross-over design study were
      given nothing per os for 36 hours, then were randomly assigned to receive either
      an oral water load (OWL; 40 ml/kg of body weight) by ruminal gavage or HSS IV (5
      ml/kg of body weight) plus OWL; 10 days later, each cow received the other
      treatment. Outcome measures included serum and urine osmolality, electrolyte (Ca,
      P, Na, K, and Cl), creatinine, blood glucose, hemoglobin (Hgb), and plasma total
      protein (PTP) concentrations; serum colloid osmotic pressure (SCOP); urine
      volume; PCV; and blood gas analytes (pH, P(CO2), P(O2), HCO3-, base excess [BE],
      and O2 saturation). RESULTS: IV administered HSS plus OWL caused Hgb, PCV, PTP,
      SCOP, blood pH, BE, HCO3-, and urine osmolality values to decrease and fractional
      excretion (FE) of electrolytes, serum osmolality, and urine volume to increase.
      Blood glucose concentration was different between treatments at 0 and 150
      minutes, and FEK, FECl, and FECa were similar by 180 minutes after OWL alone, but
      absolute excretion of Na and P and FENa and FE(P) remained high after HSS
      administration. Oral water load caused Hgb, PCV, PTP, serum electrolyte and
      creatinine, SCOP, and urine osmolality values to remain unchanged or decrease
      slowly and pH, BE, HCO3-, FECa values to increase slightly by 180 minutes.
      CONCLUSIONS AND CLINICAL RELEVANCE: IV administration of HSS plus OWL, unlike OWL
      alone, increases circulatory volume rapidly, induces slight metabolic acidosis,
      increases renal perfusion and glomerular filtration rate, and effects changes in
      serum Ca and P homeostasis that may be useful in treating sick dairy cows.

PMID- 9140568
TI  - War and the medical profession.

PMID- 9140567
TI  - Effect of intra-abdominally induced pressure on the urethral pressure profiles of
      healthy and incontinent bitches.
AB  - OBJECTIVE: To determine whether reduced pressure transmission is of importance in
      the pathophysiologic mechanism of urinary incontinence in bitches. ANIMALS: 20
      sexually intact, continent bitches and 21 spayed, incontinent bitches. PROCEDURE:
      Urethral pressure profiles before (resting) and after (stressed) insufflation of
      gas in the abdominal cavity were recorded in bitches under general anesthesia.
      Differences (stressed minus resting) were calculated for all variables. On the
      basis of these values, the pressure transmission ratio was determined. RESULTS:
      Resting pressure profiles of incontinent bitches indicated significantly (P <
      0.05) lower maximal closure pressure (4.5 +/- 3.0 cm of H2O) than did those of
      continent bitches (11.2 +/- 7.2 cm of H2O). The intra-abdominal pressure increase
      lead to a shortening of total profile length, which was equal in both groups and
      caused an increase in maximal urethral pressure. The change in maximal urethral
      pressure was significantly (P < 0.05) greater in incontinent bitches (12.4 +/-
      4.1 cm of H2O) than in continent bitches (8.8 +/- 4.5 cm of H2O). The profile
      areas and the pressure transmission ratios did not differ significantly (P <
      0.05) between the 2 groups. CONCLUSION: The effect of decreased pressure
      transmission on the urethra is not a factor in the pathophysiologic mechanism of
      urinary incontinence attributable to urethral incompetence in bitches.

PMID- 9140569
TI  - Effects of a pre-training conditioning programme on basic military training
      attrition rates.
AB  - The medical attrition rates of 4 cohorts of recruits undergoing basic military
      training (BMT) were studied. They were grouped as follows: Group A (n = 3475), a
      mixture of fit and unfit recruits; Group B (n = 2081), consisting only of fit
      recruits; Group C (n = 940) comprising only unfit recruits who underwent a 4 to 6
      weeks conditioning programme prior to being subjected to a similar 3-month BMT
      for all 3 groups and Group D (n = 2613) comprising unfit recruits who underwent
      an extended 4-month BMT. It was found that Group B [Relative risk (RR) = 0.26 95%
      confidence interval (CI) = 0.21, 0.33] and Group C (RR = 0.45 95% CI = 0.38,
      0.62) had significantly lower medical attrition rates compared with Group A (RR =
      1). Group D, however, did not show significantly lower attrition rates in spite
      of a more gradual training pace. When the unfit cohorts were compared, Group C
      (RR = 0.52 95% CI = 0.40, 0.67) had significantly lower attrition rates than
      Group D (RR = 1). The major cause of medical attrition in all groups was musculo
      skeletal injuries sustained during training. Our results showed that a formal pre
      training conditioning programme resulted in lower attrition during BMT and this
      reduction was more effective than training the recruits at a slower pace by
      extending the BMT by one month.

PMID- 9140570
TI  - Construction of a screening inventory for major mental disorder in the Army.
AB  - The development of a 29-item self-report inventory to screen for non-adaptiveness
      with an episode or a history of major mental disorder in the army is described.
      Initially, a 58-item inventory was constructed. However, through a pilot study 46
      items remained. The reliability and validity test of the 46-item inventory was
      then carried out on 357 patients and 126 controls. Firstly, item analyses were
      performed which showed 12 items that distinguished between schizophrenic patients
      and controls, 9 items that distinguished between depressive patients and controls
      and 8 items that distinguished between manic patients and controls. A final 29
      item inventory was found to have satisfactory reliability, sensitivity and
      specificity. The analyses of the best cut-off scores using the receiver-operating
      characteristic curve suggested a score of 3 for the Schizophrenia Scale, 2 for
      the Depression Scale, and 3 for the Mania Scale. The inventory can be completed
      in about 5 to 10 minutes and has a simple method of scoring. The use of this
      screening inventory in the army is discussed.

PMID- 9140571
TI  - Burkholderia pseudomallei infection in the Singapore Armed Forces from 1987 to
      1994--an epidemiological review.
AB  - Between 1987 and 1994, twenty-three cases of Burkholderia pseudomallei infection
      (melioidosis) were diagnosed in persons serving in the Singapore Armed Forces.
      There were four deaths resulting from complications of the infection. Unlike the
      situation in the general population, where the affected are mainly the elderly
      with underlying illness, the majority of cases in the Singapore Armed Forces were
      otherwise fit and healthy young servicemen. Serological surveys have shown the
      prevalence of the infection in Singapore to be 0.2% in the military as well as
      civilian population. As physical contact with soil is an unavoidable part of
      military training, military personnel continue to be at risk of exposure to this
      soil-related disease.

PMID- 9140572
TI  - Effects of optical correction media on contrast sensitivity.
AB  - Contrast sensitivity functions (CSFs) were obtained for 257 emmetropic subjects
      (514 eyes) and 35 contact lens users (64 eyes) in the Republic of Singapore Air
      Force using the Vistech Contrast Test System. For the emmetropes, contrast
      sensitivity tests were carried out with and without plano spectacles (PS). For
      the myopes, we compared their performances with spectacles, daily-wear soft
      contact lenses (CLs), and CL plus PS at Snellen visual acuities of 6/6 or better.
      Paired t-tests showed that there were no significant differences (P > 0.05) when
      CSFs of the emmetropes were measured with and without PS and when that of the CL
      users were measured with spectacles, CL and CL plus PS. We therefore conclude
      that myopic optical correction media do not retard CSF significantly based on the
      Vistech charts, although they may reduce image size and modify light transmission
      by being imperfect transparencies. The observed decrease in CSF for myopes even
      after myopic correction might therefore be related to other factors associated
      with myopia, such as retinal changes or possibly mild amblyopia.

PMID- 9140573
TI  - Effects of peripheral high energy missile trauma on the oxygenation of lung
      tissue in the pig.
AB  - The purpose of this paper was to study the effect of peripheral high energy
      missile trauma on oxygenation of the lung tissue. Eleven pigs were randomised to
      either high energy gunshot wound of the soft tissues of the thigh or sham
      exposure. Under anaesthesia and controlled ventilation, the carotid artery and
      the jugular vein were catheterised and a thoracotomy was performed. A Clark-type
      multiwire electrode was placed on the surface of the middle lung lobe for
      registration of the oxygen pressure fields of the lung tissue (PtO2). In animals
      subjected to missile trauma, an increased heterogeneity was seen in PtO2 1 and 2
      hours after exposure, specially under hypoventilatory provocation. Furthermore,
      PtO2 values did not return to baseline when hypoventilation was followed by
      normoventilation, in contrast to what was seen in the sham exposed animals. No
      differences between groups were found in arterial PO2, O2-saturation, PCO2, pH or
      in pulse frequency. These findings of disturbance in oxygenation of pulmonary
      tissue, may represent an early phase in the development of a lung injury
      resembling the post-traumatic adult respiratory distress syndrome seen in man.
      The initiating events could be release of mediators from traumatised tissue
      and/or direct effects of the shock waves from missile impact, passing through the
      body.

PMID- 9140574
TI  - Ultrastructural changes of macroglial cells in the rat brain following an
      exposure to a non-penetrative blast.
AB  - The present study examined the ultrastructural changes in astrocytes and
      oligodendrocytes in rats following an exposure to a non-penetrative blast. At 1
      and 7 days after the blast, the astrocytes in the cerebral and cerebellar cortex
      were hypertrophied; their end-feet associated with the blood vessels were also
      swollen, bearing sparsely distributed organelles. The above changes were not
      observed in experimental rats when the survival interval was prolonged. It is
      concluded from this study that the blast could have disrupted the integrity of
      the blood-brain barrier resulting in possible abnormal entry of serum-derived
      substances thereby leading to astrocytic hypertrophy. The reversible nature of
      the changes is evidenced by the seemingly normal appearance of astrocytes in rats
      killed at 14, 21 and 28 days after the blast. Oligodendrocytes remained
      unaffected at various time intervals after the blast.

PMID- 9140575
TI  - Surgical treatment of skin lesions induced by sulfur mustard ("mustard gas")--an
      experimental study in the guinea pig.
AB  - Sulfur mustard has been known as a chemical warfare agent since 1915 and its
      biological effects, e.g. acting as an alkylating agent reacting with nucleophiles
      in proteins and nucleic acids, are well known. Still, there is today no specific
      antidote against or treatment of sulfur mustard induced cutaneous lesions.
      Recently, a technique of treating thermal burns with early surgical excision
      followed by skin grafting has been established. The present study was undertaken
      to evaluate, if a similar technique could be of value in the treatment of sulfur
      mustard lesions. Under anaesthesia, guinea pigs were exposed to sulfur mustard
      vapour, followed six hours later by excision of the exposed skin segment. In
      animals where the skin defect was primary sutured, healing time was significantly
      shorter and increase in body mass greater compared to conservatively treated
      controls. No such differences were found if excision was followed by full
      thickness skin grafting. Further studies in other species are suggested to
      clarify the possible role of surgical excision of sulfur mustard skin lesions,
      followed by skin transplantation, in humans.

PMID- 9140576
TI  - Rubella seroprevalence in the Singapore Armed Forces (SAF) and the changing need
      of the SAF rubella immunisation programme.
AB  - A seroepidemiological study on the prevalence of rubella antibodies in a cohort
      of Singapore Armed Forces (SAF) recruits was conducted in 1994, twelve years
      after rubella immunisation was routinely given to primary 6 school boys in 1982.
      The results showed a high level of immunity (97.1% seropositive) in the study
      cohort. The implication of this finding is that it may no longer be necessary to
      routinely immunise recruits on entry into the SAF against rubella; the latter can
      be limited to those with no evidence of prior rubella immunisation.

PMID- 9140577
TI  - Fear of flying--a Singapore perspective.
AB  - Fear of flying is a term commonly used in the Aviation Medicine community.
      However, heterogeneous conditions which can present with fear of flying, demand
      that a more stringent and systematic approach be made in one's management of the
      aviator with fear of flying (FOF). Cases of FOF between 1974 and 1995 presented
      to the Civil Aviation Medical Board and the Aeromedical Centre of the Republic of
      Singapore Air Force were studied for their psychopathology, psychodynamics,
      diagnoses, motivation for treatment, type of treatment and response to treatment,
      and their eventual outcome in relation of flying. 53.3% of 15 cases had Adult
      Situational Reaction, 26.7% had phobia of flying, 6.6% had Adjustment Disorder,
      6.7% had Anxiety Depressive Disorder and 6.7% had Transient Psychosis. All cases
      of Adjustment Disorder were returned to flying, compared with 25% of Adult
      Situational Reaction, 66.7% of Phobia of Flying and none of the aircrew suffering
      from Transient Psychosis. Fear of flying is thus a complex phenomenon, where
      there is interaction of elements of mental health, neurotic roots, real and
      imaginary threats and life events affecting eventually the flyer's willingness to
      fly.

PMID- 9140578
TI  - The periodic medical examination in the Republic of Singapore Air Force--a
      review.
AB  - Aeromedical Examinations (AMEs) have been done in the Republic of Singapore Air
      Force (RSAF) since its beginning for licensing and monitoring health status of
      essential personnel. The rapid progress in scientific advances and medical costs
      of recent years prompted a re-evaluation of the AME as a preventive tool, both in
      accident prevention and health promotion. A retrospective cohort study of 233
      males spanning the time they joined the Air Force until 1990 was done and a
      descriptive analysis of the cohort with the incidence rate of cases picked up
      during this period was used as an indicator of usefulness of the AME. In the
      follow-up period of 2997 person-years, a small number of cases were picked up
      which resulted in two pilots being grounded permanently. Most procedures were
      found to be useful to varying extent except the routine chest X-rays which was
      found to be ineffective. Trends of biodata resulting from serial examinations are
      useful in planning and evaluation of intervention and health education programme,
      but only if the baseline measurements are accurate, hence quality control at all
      stages is important. The AME can be an effective tool for prevention if designed
      appropriately. Screening tests included must be scientific and the logic for
      selecting tests must be convincing. Most importantly, it is suggested that a
      clear and detailed medical history is the most useful component for early
      detection of problems. This is facilitated by a strong bond and rapport between
      doctors and subjects to ensure that the information is forthcoming and honest.

PMID- 9140579
TI  - An overview of recent developments in the management and research of trauma.
AB  - Trauma is one of the devastating problems of modern society. Each year, more than
      one million people die of trauma worldwide. In this paper, some of the recent
      developments in the management and research of trauma are presented: (1)
      Traumatology and injury epidemiology; (2) Trauma scoring and multiple injuries;
      (3) Blast injury and impact injury; (4) Mine injuries and firearm injury; (5)
      Classification of war wounds; and (6) Basic science research on trauma.

PMID- 9140580
TI  - Anterior knee pain in the military population.
AB  - Anterior knee pain in our military population consititutes a diagnostic and
      therapeutic problem that is not always easily solved. In recent years, a better
      understanding of the biomechanics of the patello-femoral joint has contributed to
      the successful classification and treatment of many patients. However, the cause
      of pain remains elusive in a significant subset of patients who show no clinical
      or radiographic evidence of patellar malalignment and continue to have persistent
      pain despite adequate physiotherapy. In this article, the classification and
      approach to anterior knee pain are reviewed. Emphasis is placed on dividing
      patients into four subsets namely; normal tracking, patellar tilt, patellar
      subluxation and extra-articular causes of anterior knee pain. A more rational
      approach to the problem can then be employed and successful rehabilitation and/or
      surgery can be expected.

PMID- 9140581
TI  - Hypertonic saline dextran (HSD) and intraosseous vascular access for the
      treatment of haemorrhagic hypotension in the far-forward combat arena.
AB  - Battlefield statistics show that 50% of deaths are due to acute haemorrhage.
      Hypertonic (7.5% saline)/hyperoncotic (6% Dextran-70) solution (HSD) for the
      treatment of haemorrhagic hypotension may have physiologic and logistic
      advantages over conventional fluid therapy for use in the far-forward combat
      arena. HSD rapidly expands plasma volume and stabilizes haemodynamic variables in
      various animal models of haemorrhage, at a volume dose of about 1/10 of
      conventional lactated Ringers solution. However, combat conditions, as well as
      the physiological status of the patient may result in time delays or failure to
      achieve vascular access. Over the past 5 years we have investigated intraosseous
      infusion of HSD via the sternum or tibia, as a possible means of achieving rapid
      vascular access and plasma volume expansion. These data in experimental animals
      and one clinical study show that HSD can be safely and rapidly infused via the
      intraosseous route achieving the same haemodynamic benefit as observed with
      intravenous administration.

PMID- 9140582
TI  - Psychological disorders in Singaporean national servicemen.
AB  - Young able-bodied male Singaporeans are required to undergo national service. The
      majority are able to cope with military training without developing any
      psychological disorders. A small group, however, are unable to handle the rigours
      of military training. They are identified, diagnosed and managed appropriately so
      that they can continue to serve national service within their capability. Three
      types of psychological disorders are highlighted in this paper. Type 1 cases
      refer to those with psychotic and neurotic disorders and they are usually
      downgraded to serve in non-combat vocations. The severe psychotics are exempted
      from service. Type II cases refer to those with stress-related disorders which
      are temporary conditions amenable to treatment. Many of them can return to their
      previous functioning level once their stress-related problems are resolved. Type
      III cases refer to those who capitalise on their existing physical conditions by
      complaining or exaggerating their psychological symptoms hoping to prolong their
      medical condition so that they can get an easy way out. These cases, which are in
      the minority, require firm handling, limit-setting and counselling so that they
      can learn to address their problems appropriately without resorting to
      psychological symptoms. Emphasis is given to the diagnostic approach and
      treatment of all 3 types of disorders, particularly the stress-related disorders.
      The roles of unit personnel and family members in providing a corroborative
      account of the servicemen's behaviour, work performance and inter-personal
      relationship are given special emphasis in the management of soldiers with
      psychological problems.

PMID- 9140585
TI  - An overview of the physiological effects of sustained high +Gz forces on human
      being.
AB  - In the search for the advantage in aerial combat, increasingly higher performance
      aircraft are being developed that impose ever greater acceleration force loads on
      the human pilot. The symptomatology associated with increasing +Gz acceleration
      forces, culminating in G-induced loss of consciousness caused by the cessation of
      cerebral blood circulation are described. The inability of the normal
      cardiovascular system mechanisms to provide adequate circulation to the brain and
      the eyes, and the resulting associated symptomatology and physiological changes
      are discussed. The normal weight, hydrostatic pressure and physiological
      ventilation/perfusion gradients in the lungs are exaggerated under high +Gz
      forces resulting in increased pulmonary arterio-venous shunting. This causes
      impairment of circulatory oxygenation and may also result in acceleration induced
      atelectasis. The effects of +Gz acceleration forces on the renal system and the
      limitations of the cervical musculature are also discussed. This paper serves to
      describe the human physiological responses to increased +Gz acceleration forces
      in an attempt to provide a better understanding of the body's reaction to such
      demanding physical stressors.

PMID- 9140583
TI  - Traumatic stress--an overview of diagnostic evolution and clinical treatment.
AB  - This paper provides an overview of recent advances in the study of traumatic
      stress, with a special focus on the categorical and conceptual evolution in
      aetiological, diagnostic classification of post traumatic stress disorder (PTSD).
      A review update on psychological and pharmacological therapies relevant to the
      management of PTSD, and the trend towards a multi-layered, biopsychosocial
      approach is discussed. This review also includes an update of the risk factors
      and mediating factors associated with post traumatic responses.

PMID- 9140586
TI  - Pharmacology and toxicology of chemical warfare agents.
AB  - Toxic chemicals have been used as weapons of war and also as means of terrorist
      attacks on civilian populations. The main classes of chemical weapons are: a)
      nerve agents, b) vesicant agents and c) blood agents. If an exposure to nerve
      agents is anticipated, prophylactic pyridostigmine may be used. Once exposure has
      occurred, the management strategy is to reduce cholinergic activity through the
      use of atropine as well as to attempt to regenerate acetylcholinesterase with
      pralidoxime. Convulsions may be managed using diazepam. Exposure to vesicant
      agents may be reduced through the use of protective gear, but once exposure has
      occurred, no specific treatment is available. Treatment remains symptomatic and
      supportive. Lethal atmospheric concentrations of hydrogen cyanide gas, a blood
      agent, is seldom achieved except in enclosed spaces. Sub-lethal exposure to
      hydrogen cyanide may be managed using sodium nitrite, sodium thiosulphate and
      VitB12.

PMID- 9140584
TI  - Effects of sleep deprivation with reference to military operations.
AB  - This review discusses the need for sleep, effects of sleep deprivation on
      behaviour and performance in the military, and sleep management recommendations
      to optimise combat effectiveness. Most people, regardless of sex or race, prefer
      7 to 8 hours of sleep each night. Sleeping during the day is less recuperative.
      Continuous sleep is more effective than multiple short naps-even when the total
      hours for naps is more. Ten to 20 minute naps are useful when continuous sleep is
      not possible. Sleep inertia is the 5 to 30 minute period of sluggishness after
      awakening and important military tasks should be avoided. Previously, continuous
      work episodes (CWEs) duration was restricted by limited night vision, unreliable
      equipment and reduced endurance of military personnel. With improved technology,
      CWEs are now restricted primarily by endurance which is affected by sleep
      deprivation. This was one of the experiences noted in recent conflicts (e.g.
      Desert Storm) by personnel in the air force, army and navy. Since there will be
      changes in operational requirements, several work-rest-sleep plans must be
      prepared. Sleeping the preferred 7 to 8 hours per 24 hours the week before an
      operation may help prepare for optimal performance. Personnel should be
      familiarised with conditions under which they may sleep. During combat, sleep
      management should ideally avoid situations where all personnel are exhausted at
      the same time. As sleep debt accumulates, a person's mood, motivation, attention,
      alertness, short-term memory, ability to complete routines, task performance
      (errors of omission more than errors of commission) and physical performance will
      become more negatively affected. Counter measures must then be taken (e.g. time
      for sleep or naps, changing routines or rotating jobs). Drugs like caffeine and
      amphetamine can help personnel stay awake. However, they may also keep them awake
      when they need to sleep- and on awakening, they could suffer from "hang-overs"
      and are less efficient. Sleep lost need not be replaced hour-for-hour. Therefore,
      after operations, personnel need continuous sleep for only 10 to 12 hours as
      longer sleep increases sleep inertia and delays getting back to normal schedules.

PMID- 9140587
TI  - Management of concomitant maxillofacial, cervical spine and laryngeal trauma-
      case reports.
AB  - Three cases are presented to stress important points in the diagnosis and
      management of concomitant maxillofacial, cervical spine and laryngeal trauma.
      Emergency tracheostomy to control airway, immediate rigid fixation of
      maxillofacial fractures, early computed tomographic (CT) scans to evaluate the
      extent of laryngeal and cervical spine injury and the early repair of laryngeal
      injury will provide better aesthetic and functional results.

PMID- 9140588
TI  - Management of post traumatic stress disorder using combat stress treatment
      principles--a case report.
AB  - Combat stress casualties are only generated by war. However, military
      psychiatrists need to acquire the experience and skills that they would need
      before they are ever faced with their first combat stress casualty. Non-combat
      post traumatic stress disorder patients present the best approximation to combat
      stress casualties. This case study demonstrates how combat stress treatment
      principles can be successfully applied to a case of non-combat post traumatic
      stress disorder patient. It is not the intention of this paper to demonstrate
      whether the combat stress management protocol is superior to other methods or
      protocols. Recommendations are made on methods to identify post traumatic stress
      disorder patients and how to seize every available opportunity to practise combat
      stress treatment principles.

PMID- 9140589
TI  - Virtual reality and telepresence for military medicine.
AB  - For decades, warfighters have been putting in place a sophisticated "digital
      battlefield", an electronic communication and information system to support
      advanced technology. Medicine is now in a position to leverage these technologies
      to produce a fundamental revolution, and the keystone is the digital physician.
      Today nearly all information about a patient can be acquired electronically, and
      with the new technologies of teleoperation and telesurgery we can provide remote
      treatment and even surgery through telemedicine. The following framework for
      military medicine will leverage upon the current electronic battlefield. A
      personnel status monitor (PSM) will have a global positioning locator to tell the
      position of each soldier and a suite of vital signs sensors. When a soldier is
      wounded, the medic will instantly know the location of the soldier, and how
      serious is the casualty. This will permit the medic to locate the most critically
      wounded soldier. Once stabilised, he will be placed in a critical care pod, a
      fully automated intensive care unit in a stretcher, which will monitor his vital
      signs, administer fluids and medications and provide environmental protection. If
      immediate surgery is needed, a remote telepresence surgery vehicle will come to
      the wounded soldier, the medic will place him in the vehicle, and a surgeon will
      operate remotely using telepresence surgery from a distant Mobile Advance
      Surgical Hospital (MASH) to the combat zone. Also, the expertise from any
      specialist will be available from the rear echelons as far back as the home
      country. For education and training in combat casualty care, virtual reality
      simulators are being implemented. This same scenario can be utilised in civilian
      health care, especially in providing care to patients in remote areas who do not
      currently have access to simple, let alone sophisticated, health care.

PMID- 9140590
TI  - Coinfection and genetic recombination between HIV-1 strains: possible biological
      implications in Australia and South East Asia.
AB  - It has been recognised that human immunodeficiency virus (HIV) mutates rapidly
      and that nucleotide substitutions, deletions, insertions, and rearrangements
      resulting from recombination events are the main factors that result in variation
      of the HIV-1 genome. Together, these processes are actively contributing to the
      diversity and virulence of viral forms comprising the acquired immune deficiency
      syndrome (AIDS) pandemic. There are 9 HIV-1 subtypes recognised (A-H and O),
      based on the envelope region segments. Inter-subtype recombination has been
      already described, whereas intra-subtype recombination has been difficult to
      detect. In this study, we have identified in vivo genetic recombination between
      HIV-1 strains belonging to subtype B in a patient who presented both intravenous
      drug use (IVDU) and homosexual sex as risk factors. Genetic analysis of viral
      strains in the hypervariable V3 region of the envelope gene indicated the
      presence of three distinct sequence groups categorized according to their
      respective tetrapeptide motifs-GPGR, GLGR and GPGK. Detailed genetic and
      phylogenetic analyses suggested the recombination occurring only between sequence
      groups with GPGR and GPGK tetrapeptide motifs. These data suggest that
      coinfection with closely related strains can occur in vivo, and the generation of
      hybrid HIV-1 genomes via genetic recombination between subtype B strains can
      result in further antigenic diversity which may thwart diagnosis and future
      vaccine efforts. Since HIV-1 subtype B is still the most commonly found subtype
      around the globe, the hybrid genomes between different subtype B strains may
      result in epidemiologic shifts and altered pathogenesis.

PMID- 9140592
TI  - Penetrating keratoplasty for keratoconus.
AB  - Keratoconus is a common corneal dystrophy in which penetrating keratoplasty is an
      effective form of treatment. A retrospective study on patients with keratoconus
      who underwent penetrating keratoplasty in the Singapore National Eye Centre
      between 1991 and 1995 was undertaken to describe and characterise the patient
      population and the success of this procedure. Thirty-two penetrating
      keratoplasties for keratoconus in 32 eyes of 29 patients were identified. Twenty
      eyes of 20 patients had a postoperative follow-up period of at least 12 months
      (range 12 to 44 months). These eyes were specifically examined for success rate
      and complications. Of the 32 eyes in the study, 18 (56%) belonged to Indians
      patients and 23 (72%) belonged to male patients. In those eyes with 12 months or
      more of postoperative follow-up, the visual acuity of 16 (80%) eyes improved
      postoperatively, with 14 (70%) eyes having a best corrected visual acuity of 6/12
      or better. There were no graft failures. Nine eyes (45%) had complications
      postoperatively. Five eyes underwent refractive surgery for correction of
      astigmatism. Useful vision of 6/60 or better was achieved within 1 week
      postoperatively in 8 (40%) of the eyes. The authors conclude that penetrating
      keratoplasty is a successful procedure in keratoconic eyes not correctable by
      conservative therapy. The incidence of postoperative complications were however
      not uncommon. Although the majority of these complications were treated
      successfully, severe complications such as retinal detachment and glaucoma were
      the main causes of poor visual outcome after penetrating keratoplasty for
      keratoconus.

PMID- 9140591
TI  - Radioiodine (I-131) therapy and the incidence of hypothyroidism.
AB  - Radioiodine (I-131) is one of the accepted forms of treatment for thyrotoxicosis.
      The major drawback of this treatment is the definite incidence of hypothyroidism,
      which is either early or late, and is cumulative. We set out to analyse the local
      incidence of this outcome. Patients with hyperthyroidism, treated with
      radioiodine from 1984 to end of 1989, and still on follow-up with the Department
      of Nuclear Medicine, Singapore General Hospital were analysed for the incidence
      of hypothyroidism. Three hundred and eighty-two patients were analysed (305
      females, 77 males). Their ages ranged from 14 to 85 years (mean 48.2, SD 11.1
      years). The doses of radioiodine ranged from 4 to 18 mCi (mean 7.6 mCi, SD 1.8
      mCi). Two hundred and sixty-two patients who received I-131 only required a
      single dose, while 87 needed one repeated dose of I-131, and 33 needed more than
      2 doses. Of the 382 patients, 271(70.9%) became clinically hypothyroid, 6 (1.6%)
      were subclinically hypothyroid, 100 (26.7%) were euthyroid and 3 (0.8%) remained
      hyperthyroid. One hundred and eighty-one patients (47.4%) were clinically
      hypothyroid at the end of 1 year, and an average rise of 4.8% per year was
      observed from the second to the fifth year. From the sixth year onwards, the
      average incidence of hypothyroidism was 1% per year. I-131 is indeed an effective
      means of controlling thyrotoxicosis (99.2% were no longer hyperthyroid). The main
      problem with this treatment is hypothyroidism, and this is easily managed with L
      thyroxine.

PMID- 9140593
TI  - Case reports on acute toluene poisoning during parquet flooring.
AB  - We report two cases of acute toluene poisoning occurring during parquet flooring.
      Inhalation is the major route of absorption in the workplace, owing to the high
      volatility of the compound. Such patients should be monitored closely for
      respiratory distress, central nervous system (CNS) depression and cardiac
      arrhythmias. Both our patients manifested signs of CNS depression and one had
      bronchospasm aborted by salbutamol Industries using toluene must ensure that
      precautions like adequate ventilation are taken to protect their workers.

PMID- 9140594
TI  - Fasting total plasma homocysteine and atherosclerotic peripheral vascular
      disease.
AB  - Fasting total plasma homocysteine levels were measured by rapid ion-exchange
      chromatography in 100 patients with symptomatic atherosclerotic peripheral
      vascular disease (PVD) and 100 age and sex-matched control subjects. Demographic
      data, biochemistry, hematology, and lipid fractions were measured in both groups,
      and clinical and vascular laboratory disease parameters were recorded for the
      patient group. Patients with hyperhomocysteinemia (defined as those with fasting
      homocysteine values exceeding the 90th percentile of the control range) were
      compared to patients with normal homocysteine with respect to the above
      parameters. Total fasting homocysteine concentrations were significantly higher
      in the patient group (28.8 +/- 14.9 mumol/l) than in the control subjects (20.3
      +/- 11.3 mumol/l; p < 0.001). Homocysteine levels were also higher in males than
      in females in both the control and the patient groups. Homocysteine correlates
      positively only with age in the healthy controls (r = 0.291; p < 0.005) but not
      with other standard risk factors. Multivariate analysis of the biochemical risk
      factors confirmed that total plasma homocysteine concentration is an independent
      risk factor for PVD (p < 0.001). Hyperhomocysteinemia is not associated with
      vitamin B12 or folate deficiency states. Vitamin B12 concentration was 591 +/-
      313 ng/l in the control group, and 682 +/- 405 ng/l in the patient group (p =
      NS). Serum folate concentration was lower in the controls (7.2 +/- 2.3
      micrograms/l) than in the patients (8.3 +/- 2.0 micrograms/l, p < 0.001). Mild
      hyperhomocysteinemia was detected in 27% of the patients. Patients with
      hyperhomocysteinemia has a four-fold increase in risk of PVD relative to patients
      with a normal homocysteine level. There is no significant difference between the
      two groups with respect to patient demographics, biochemical risk factors, and
      disease pattern and severity.

PMID- 9140595
TI  - Patients with diabetes and critical limb ischemia have a high peripheral vascular
      resistance.
AB  - Results of infrainguinal bypass surgery may be better in diabetic patients
      compared with nondiabetic patients. One important determinator of outcome in
      these operations is the peripheral vascular resistance (PR). The aim of the
      present prospective study is to evaluate whether there is a difference in PR in
      diabetic and nondiabetic patients with critical limb ischemia. The two patient
      groups (n = 11 for each) were matched for toe pressure, age, gender, and outflow
      vessel, PR was measured intraoperatively during infrainguinal bypass surgery by
      controlled infusions of autologous blood. The resistance was significantly higher
      in the diabetic group (p < 0.05), as compared to the nondiabetic group. Except
      for fibrinogen that tended to be higher in diabetics (p = 0.07), blood
      parameters, blood pressures and angiographic scoring of run-off were similar in
      both groups. This finding of higher PR in diabetic patients with critical limb
      ischemia compared with matched nondiabetic ischemic patients suggests that a low
      PR is not the reason for the positive results of infrainguinal bypass surgery in
      diabetic patients.

PMID- 9140596
TI  - Femorodistal bypass using cryopreserved venous allografts for limb salvage.
AB  - Critical ischemia due to extensive femoropopliteal occlusive disease often leads
      to amputation in patients in whom an autologous vein is unavailable for
      reconstruction. The purpose of this nonrandomized prospective study is to
      evaluate the usefulness of cryopreserved venous allografts (CPVA) as an arterial
      substitute in these cases. Between October 1990 and March 1993, long bypass to a
      tibial or a foot artery using a CPVA was performed in 25 consecutive patients
      with ulcerations or gangrene. There were 19 women and six men with a mean age of
      72 years (range: 51-90). The indication for allograft reconstruction was absence
      (17 cases) or unsuitability (eight cases) of an autologous vein graft. Greater
      saphenous vein allografts were harvested from multiple organ donors and frozen at
      -80 degrees C with 12% dimethylsulfoxide (DMSO). Sixteen patients had undergone
      one or more previous unsuccessful limb salvage attempts. The plantar arch was
      absent or incomplete in 16 patients (64%). Patients were followed up
      prospectively for a mean of 21 months (range: 3-32). One patient died early (32
      days) and three patients died late with patent bypasses. Cumulative survival rate
      was 77% at 1 year and 72% at 2 years. Cumulative secondary patency rate (Kaplan
      Meier) was 88% at 1 months, 72% at 6 months, and 52% at 1 year. The cumulative
      limb salvage rate was 78% at 2 years. When an autologous vein is unavailable,
      long bypass using a CPVA is a simple, quick, minimally traumatic, economical, and
      effective method to achieve limb salvage in patients with severe distal arterial
      occlusive disease. However, CPVA causes immunoreaction and there is a risk of
      proximal postanastomotic stenosis. Doppler ultrasound surveillance of a
      subcutaneous graft allows accurate assessment and repair of the abnormalities
      with no increase in mortality or morbidity.

PMID- 9140597
TI  - Below-knee bypass using fresh arterial allografts for limb salvage: early
      results.
AB  - The purpose of this study was to evaluate early results of below-knee bypass
      using fresh arterial allografts as arterial substitutes for limb salvage. From
      April 1991 to September 1993, we performed 28 below-knee bypass procedures using
      fresh arterial allografts in patients without a suitable autologous vein.
      Allografts were obtained by multiorgan harvesting from brain-dead subjects and
      preserved at 4 degrees C. Histologic examination of grafts was carried out.
      Secondary patency at 2 years calculated using the Kaplan-Meier method was 64%
      (confidence interval [CI] 45%-79%). No signs of graft deterioration or rejection
      were noted. These preliminary results are encouraging but long-term assessment is
      needed before expanding the range of application.

PMID- 9140598
TI  - Lower extremity bypass for critical ischemia using synthetic conduit and adjuvant
      vein cuff.
AB  - The use of an interposition cuff of vein placed at the distal anastomosis between
      synthetic bypass conduit and outflow vessel has been advocated to improve patency
      of lower extremity bypass grafts. Over a three-year period we have performed 43
      such bypass procedures: to the above knee popliteal artery (n = 3); below knee
      popliteal (n = 13), and infrapopliteal arteries (n = 27). There were 20 females
      and 23 males having a mean age of 70 years (48-84 years). Fifteen patients were
      hypertensive, 15 were diabetic, and 25 had a history of tobacco use. All cases
      required limb salvage for rest pain (n = 25), gangrene (n = 10), or ulceration (n
      = 8) in the absence of suitable autologous vein. Nineteen operations followed a
      previous failed bypass. Patients were reviewed at six-month intervals. The
      operative mortality was 8% and two-year primary and secondary patency were 40%
      and 55%, respectively. Cumulative patency rates were better for first-time
      grafting procedures than for patients who had undergone previous attempts at limb
      salvage (60% versus 22%). Two-year limb salvage was 60%. During the same time
      period, two-year primary and secondary patency rates were 54% and 67%,
      respectively for autogenous vein. Although the numbers are small these results
      support the use of an adjuvant vein cuff when employing synthetic grafts. A
      prospective study of vein versus synthetic graft plus cuff should be undertaken.

PMID- 9140599
TI  - Subclavian vein thrombosis: outcome analysis based on etiology and modality of
      treatment.
AB  - Therapeutic options for subclavian vein thrombosis (SVT) include anticoagulation,
      thrombolysis, endovascular repair, and direct surgical intervention. The most
      effective method of treatment remains undetermined. We reviewed our institutional
      experience over 7 years with SVT patients to compare the results of treatment
      based on etiology of thrombosis. Nineteen patients suffered SVT secondary to
      malignancy, catheter placement, radiation, or hypercoagulability. Thirteen were
      Paget-Schroetter (PSS), or primary effort-related SVT. Patients with dialysis
      access procedures were excluded. Thrombolysis was initiated in 31/32 patients.
      Success was defined as complete obliteration of clot. Adjunctive treatment to
      relieve external compression or improve lumenal contour was performed on 16/32
      patients (eight PSS, eight secondary SVT). Success of adjunctive treatment was
      defined as return to baseline activity without symptoms. Objective follow up
      (venography or duplex scanning) was included when available. Adjunctive treatment
      included balloon angioplasty (6), stent placement (5), first rib resection and
      scalenectomy (4), and vein reconstruction (4). Initial treatment success with
      thrombolysis was achieved in 26/31 patients (84%). Angioplasty failed in three
      PSS and three secondary SVT patients. Stent placement was successful in 2/5
      patients (both secondary SVT). Surgery was performed only on PSS patients: first
      rib resection and scalenectomy succeeded 4/4 times, vein reconstruction 2/4.
      Twenty-eight patients were given long-term therapy with oral anticoagulation with
      good long-term results. Seven patients experienced complications, including one
      death. Results of SVT therapy including thrombolysis and oral anticoagulation are
      very good. Angioplasty and stent placement in secondary SVT patients appears to
      add little long term benefit. Surgery may improve outcome in selected PSS
      patients, although the additional benefit could not be determined by the design
      of this study. Evaluation and treatment limited only to PSS excludes the majority
      of SVT patients.

PMID- 9140600
TI  - Endovascular repair of peripheral aneurysms, pseudoaneurysms, and arteriovenous
      fistulas.
AB  - Endovascular repair of peripheral arterial lesions was performed in 10 patients
      including two iliac aneurysms, two iliac anastomotic pseudoaneurysms, one
      subclavian pseudoaneurysm, one axillary anastomotic disruption, two prosthetic
      pseudoaneurysms, and two posttraumatic arteriovenous (AV) fistulas. The
      indications for repair were aneurysm size in five cases, massive hematoma in one,
      threatened prosthetic dialysis graft in two, venous hypertension with non-healing
      ulcer in one, and arm pain in one. Vascular access was obtained through surgical
      cutdown in all cases, via the femoral artery in five patients, the proximal
      brachial artery in three and a prosthetic graft in two. Stented prosthetic grafts
      were used in five cases (1 polyester and polytetrafluoroethylene 4 [PTFE]), and
      PTFE-covered stents in five cases. Concomitant procedures were done in four
      patients including two open repairs of a common femoral artery aneurysm, a
      transluminal dilatation of a proximal aortic anastomotic stenosis, and an iliac
      artery transluminal angioplasty. Eight of 10 cases were technically successful.
      Completion arteriography revealed complete exclusion of all lesions, except for
      one minimal proximal stented graft leak in a pseudoaneurysm, and an incomplete
      obliteration of an AV fistula. No complications occurred. Operative time ranged
      from 45 min to 5 hours. Postoperative hospital stay was 1 day in five patients, 2
      days in three patients, and 4 days in two patients. Follow-up contrast CT scan,
      arteriography, or duplex scanning demonstrated complete exclusion of all lesions
      except an AV fistula, and decrease in size in three aneurysms. The proximal leak
      initially present in a stented graft resolved. All grafts and covered stents
      remained patent at 2-19 months of followup. Endovascular exclusion of peripheral
      arterial aneurysms, pseudoaneurysms, and AV fistulas can be done with a high
      degree of technical success, low morbidity, and short hospital stay. Short-term
      follow up is encouraging, however, long term follow up of these procedures is
      warranted to assess durability of the repair and absence of complications.

PMID- 9140601
TI  - Preoperative testing before carotid endarterectomy: a survey of vascular
      surgeons' attitudes.
AB  - Traditional surgical practice and published consensus statements from major
      vascular surgery specialty societies have considered contrast arteriography to be
      a routine part of the diagnostic evaluation prior to carotid endarterectomy
      (CEA). However, some surgeons now omit routine preoperative arteriography if a
      technically adequate carotid duplex scan is performed and indications for CEA are
      clear. To better establish current practice patterns and to characterize vascular
      surgeons' opinions about the role of preoperative arteriography, the Peripheral
      Vascular Surgery Society membership was surveyed by mail. Eighty-six percent of
      the members responded (430 of 502). Ninety-three percent of all patients
      considered for CEA are evaluated with duplex scanning; 82% with arteriography.
      While the majority of surgeons typically obtain both a duplex scan and an
      arteriogram, 70% have performed CEA without a preoperative arteriogram. Brain
      imaging studies (CT or MRI) are obtained in 26% and MR angiograms in 10% of
      cases. Seventy-five percent of the surgeons agreed with the statement that CEA
      without preoperative arteriography is an acceptable practice if appropriate
      indications for surgery are present. Furthermore, one third believed that CEA
      without a preoperative arteriogram is generally acceptable (acceptable more than
      half the time). Respondents were stratified by surgical experience time in
      practice and practice type. No significant differences in responses were found,
      suggesting the acceptance of CEA without preoperative arteriography is broad
      based. This survey demonstrates changing attitudes among practicing vascular
      surgeons regarding the necessity for routine arteriography prior to CEA. Carotid
      endarterectomy on the basis of duplex scanning and clinical assessment should be
      considered an accepted alternative.

PMID- 9140602
TI  - Video-assisted aortofemoral bypass: results in seven cases.
AB  - Between September 1995 and February 1996 we attempted to perform video-assisted
      aortofemoral bypass in nine patients. All patients were male with a mean age of
      58.7 years, mean weight of 64.7 kg, and mean height of 1.69 m. In two patients it
      was necessary to switch to open laparotomy due to inadequate aortic exposure in
      one and extensive aortic calcification in the other. Aortobifemoral bypass was
      performed by the transperitoneal approach in three patients and unilateral
      aortofemoral bypass by the retroperitoneal approach in four patients. Exposure
      was more difficult by the transperitoneal approach. Postoperative graft patency
      was excellent in all patients. Video-assisted surgery did not shorten the delay
      to resumption of intestinal transit but it did reduce the duration of
      hospitalization and need for postoperative analgesia. Our experience suggests
      that video-assisted aortofemoral bypass without laparotomy can be performed and
      that it allows more rapid patient recovery.

PMID- 9140603
TI  - Directional atherectomy and balloon angioplasty for lower extremity arterial
      disease.
AB  - This study was undertaken to evaluate the use of directional atherectomy, balloon
      angioplasty, and video angioscopy in highly selected patients with superficial
      and popliteal artery stenoses. Directional atherectomy and balloon angioplasty
      for superficial femoral and popliteal artery stenosis (> 80%) were performed in
      96 limbs (88 patients) between 1990 and 1994. All procedures were performed by
      the authors with angioscopy and C-arm angiography. Society for Vascular
      Surgery/International Society for Cardiovascular Surgery (SVS/ISCVS) categorical
      classification of chronic limb ischemia and run off scoring was utilized pre- and
      postoperatively to assess outcome. The indicators for atherectomy were moderate
      claudication (category 2, 15% of limbs), severe claudication (category 3, 65%),
      ischemic rest pain (category 4, 12%), and tissue loss (category 5, 12%).
      Morbidity was 6.0% with no perioperative mortality. All technically and
      (angiographically) successfully treated patients demonstrated postoperative
      improvement. Clinical assessment, vascular laboratory studies (outcome criteria),
      and/or angiography were monitored at follow-up visits. Intraoperative failures
      occurred in 6% of limbs due to inability to pass a guide wire (3%), impacted
      atherectomy catheter (1%), or vessel perforation (2%). In the remaining 90 limbs,
      23% failed due to either progression of disease (7.7%) or restenosis at the
      original site (15.3%). Seventy-one percent of limbs maintained their
      postoperative categorical improvement at a mean follow up of 24 months. Combining
      atherectomy and balloon angioplasty may be more durable than angioplasty or
      atherectomy alone. A long-term prospective study of the role of directional
      atherectomy and balloon angioplasty by vascular surgeons appears to be warranted
      utilizing SVS/ISCVS guidelines for lower extremity chronic ischemia categories,
      run-off score, and outcome criteria for patency.

PMID- 9140605
TI  - Aortic transgraft hemorrhage after systemic thrombolytic therapy.
AB  - Aortic transgraft hemorrhage is an unusual complication following thrombolytic
      therapy that can occur months to years after aortic surgery. It is critical to
      differentiate this from other potential causes of hemorrhage, such as an acute
      bleed from an anastomotic false aneurysm which is a surgical emergency. One such
      case that was managed conservatively with success is reported.

PMID- 9140604
TI  - Morphology and function of preserved microvascular arterial grafts: an
      experimental study in rats.
AB  - The aim of this study is to examine the morphology and function and small
      caliber, arterial grafts after preservation in the University of Wisconsin
      solution (UW). Rat carotid arteries were stored in UW (n = 10) or in phosphate
      buffered saline (PBS) (n = 10) for 1, 3, 7, and 14 days and were examined with
      light microscopy (LM) and scanning electron microscopy (SEM). Rat aortic
      preparations were stored in UW or PBS for 1 hour, 24 hours, 72 hours, 7 days, and
      14 days and assessed for functional responses (stimulated contraction and
      endothelium-dependent relaxation). Segments (5 mm) of rat carotid arteries were
      stored in UW or PBS for 3 days, 7 days, and 14 days and orthotopically implanted
      as autografts and allografts. No immunosuppressive or anticoagulant agents were
      used. After 28 days of implantation, the grafts were assessed for patency and
      excised for LM and SEM. In UW, the endothelial layer remained intact up to 9 days
      of storage. In PBS, the endothelial layer showed deterioration after 1 day and
      was completely lost after 3 days. Functional responses were demonstrated to exist
      for as long as 7 days storage in UW. In PBS, no responses could be evoked after
      24 hours storage. Autografts preserved in UW for 3 days (n = 6), 7 days (n = 6),
      and 14 days (n = 6) showed patency rates of 83.3%, 66.6%, and 66.6%,
      respectively, whereas patency rates of allografts were 66.6%, 33.3%, and 33.3%,
      respectively. Autografts stored in PBS for 3 days (n = 6), 7 days (n = 6), and 14
      days (n = 6) showed patency rates of 33.3%, 33.3%, and 50%, respectively, whereas
      patency rates of allografts were 16.7%, 0%, and 33.3%, respectively. The UW
      preserved autografts showed normal morphology. All other groups showed vessel
      wall degeneration which in the allograft groups, were accompanied by
      lymphocellular infiltration. In conclusion, the endothelial layer and vessel wall
      of arteries are adequately preserved in UW. Functional responses are retained up
      to 14 days storage in UW, but, are lost after 24 hours storage in PBS. Autograft
      implantation studies accordingly show good performance of arterial segments
      preserved in UW, whereas allografts are subject to degradation as a result of
      rejection.

PMID- 9140606
TI  - Successful treatment of an iatrogenic infrarenal aortic dissection with serial
      Wallstents.
AB  - We report a patient who presented with acute lower extremity ischemia 13 days
      following removal of an intraaortic balloon pump. Dissection of the infrarenal
      aorta, extending into the left iliac artery, was found at operation. The
      patient's recent myocardial infarction, prolonged ischemia with compartment
      syndrome, otherwise normal aortoiliac and infrainguinal arteries and the
      necessity for suprarenal aortic clamping for surgical repair, were all factors in
      the decision for endovascular repair of the dissection. Infrarenal aortic and
      left iliac Wallstents, placed intraoperatively, successfully occluded the false
      lumen of the dissection. The patient was discharged after an uncomplicated
      recovery and is asymptomatic with palpable pedal pulses and triphasic pedal
      Doppler waveforms 1 year following the procedure.

PMID- 9140608
TI  - "Above-under" exposure of the first rib: a modified approach for the treatment of
      thoracic outlet syndrome.
AB  - To provide both adequate exposure of the structures of the thoracic inlet and
      make removal of the antero-medial portion of the first rib easier, the authors
      recommend that the customarily used anterior supraclavicular approach for the
      treatment of thoracic outlet syndromes should be modified by performing through
      the same incision an additional transmuscular exposure of the first rib below the
      clavicle to facilitate its removal.

PMID- 9140607
TI  - Infected false hepatic artery aneurysm after orthotopic liver transplantation
      treated by resection and reno-hepatic vein graft.
AB  - Vascular complications after liver transplantation are relatively rare.
      Thrombosis of the host-transplant arterial anastomosis is the most frequently
      encountered vascular complication whereas only a few observations of infected
      anastomotic aneurysms, often leading to death by massive bleeding or loss of the
      transplant, have been reported. We report herein the case of a patient with an
      infected false anastomotic aneurysm of the hepatic artery associated with
      dissection of the celiac artery following orthotopic liver transplantation in a
      35-year-old man who had received a liver transplantation for end-stage liver
      disease secondary to posthepatitis cirrhosis in March 1989. Starting at day 30,
      he had signs of infection associated with hemocultures positive for
      Staphylococcus aureus. A subhepatic collection was found on sonography and CT
      scan and also cultured positive for the same germ. Arteriograms demonstrated a
      celiac artery dissection associated with a false anastomotic aneurysm of the
      hepatic artery. Surgical treatment consisted of arterial reconstruction using a
      saphenous vein graft between the right renal artery and the hepatic artery of the
      transplant, followed by resection of the hepatic artery aneurysm and the celiac
      artery. Hepatic ischemia was 12 min. The immediate postoperative course was
      uneventful and postoperative angiograms showed that the reconstruction was patent
      at 5 years.

PMID- 9140609
TI  - The role of nitric oxide in vascular biology and pathobiology.

PMID- 9140610
TI  - Surgical treatment of thoracic outlet compression syndromes: diagnostic
      considerations and transaxillary first rib resection.

PMID- 9140611
TI  - Cryo-stripping: an alternative to perforate-invaginate stripping.

PMID- 9140612
TI  - Aortoiliac bypass in a renal transplant patient using a new technique.

PMID- 9140613
TI  - Influence of artificial stimulation on unprocessed and Percoll-washed
      cryopreserved sperm.
AB  - The ability of pentoxifylline and 2-deoxyadenosine to stimulate sperm motility
      and motion characteristics was assessed in unprocessed and processed (Percoll
      separated) cryopreserved specimens. Specimens from 12 healthy volunteers were
      obtained, and the motion characteristics were analyzed; half the sample was
      immediately cryopreserved and the other was washed using the Percoll gradient
      technique. To study stimulation, samples were thawed and divided into four
      aliquots: One was used as a control, and the others were incubated with 2.5 mM 2
      deoxyadenosine, 2.5 mM pentoxifylline, or 5.0 mM pentoxifylline for 60 min. Sperm
      characteristics were analyzed on a sperm motion analyzer at 0 and 60 min
      incubation. In both unprocessed and processed samples, percentage motility
      improved significantly after stimulation with 2-deoxyadenosine or pentoxifylline
      (p = .003 or p = .0002, respectively); other characteristics improved to varying
      extent after 2-deoxyadenosine or pentoxifylline stimulation. Comparison after
      stimulation revealed that sperm motion characteristics in the unprocessed
      specimen were similar to sperm motion characteristics in the processed group.

PMID- 9140614
TI  - Synthesis of ether lipids and phosphatidylethanolamine by ejaculated human
      spermatozoa.
AB  - Ether lipids are the 1-O-alkyl derivatives of phospholipids. In contrast to
      nongerminal tissues where the plasma membrane content of ether lipids is low,
      over 40% of the phospholipids present in sperm plasma membranes are ether lipids.
      This study was undertaken to determine whether ejaculated human serm could
      synthesize ether lipids either through reacylation of 1-alkyl-sn-2
      lysophosphatidylcholine or through direct incorporation of 1-hexadecanol into
      diacyl phosphatidylcholine or diacyl phosphatidylethanolamine. The ability of
      sperm to reacylate 1-acyl-sn-2-lysophosphatidylethanolamine was also assessed. In
      these experiments, freshly ejaculated sperm were unable to reacylate a
      phosphocholine lyso ether lipid with either palmitic (16:0) or docosahexaenoic
      (22:6) acids. In contrast, sperm readily incorporated both 16:0 and 22:6 into 1
      acyl lysophosphatidylethanolamine. Similarly, sperm freely incorporated 1
      hexadecanol into diacyl phosphatidylethanolamine thus forming a 1-alkyl
      phosphoethanolamine ether lipid. Diacyl phosphatidylcholine could not serve as a
      substrate in this reaction. It is apparent, based on these data, that human
      spermatozoa can directly synthesize phosphoethanolamine ether lipids that may
      subsequently undergo exhaustive methylation to form phosphocholine ether lipids.

PMID- 9140615
TI  - Histone kinase activity of buffalo sperm chromatin.
AB  - Phosphorylation of buffalo sperm chromatin proteins under optimum conditions (8
      mM Mg2+, pH 8.0, and at 30 degrees C) using [gamma-32P]ATP and endogenous protein
      kinase activity was linear for 15 min incubation time and up to 330 micrograms
      protein. The 32P transferred from [gamma-32P]ATP was located in protein as a
      phosphoester bond. Fractionation with 1.2 M NaCl-4 M urea-0.2 M 2-mercaptoethanol
      1 mM PMSF followed by acid treatment solubilized 87% of the total chromatin
      proteins termed "sperm histones." The remaining 21% nonhistone protein was
      tightly bound to DNA. Follow-up of the label showed 91% of the 32P in sperm
      histone and 9% with DNA-associated proteins. Histone kinase activity was
      solubilized with 0.35 M NaCl, which extracted 70% of the initial enzyme activity
      associated with chromatin. Of the different histones tested as substrates,
      histone kinase phosphorylated only histone H3 and, therefore, is highly specific
      for arginine rich histone. It also phosphorylates the acidic protein, casein.
      Cyclic AMP at concentrations up to 50 microM had no effect on the phosphorylation
      of histone H3. Phosphoamino acid analysis using histone H3 as the substrate
      showed serine to be the acceptor amino acid for phosphoester link.

PMID- 9140616
TI  - Hyperprolactinemia in men with asthenozoospermia, oligozoospermia, or
      azoospermia.
AB  - The role of serum prolactin (PRL) in male infertility is still unclear. To assess
      the clinical significance of PRL determination during infertility studies, serum
      hormones and semen samples from 167 men attending the Andrology Clinic were
      analyzed, and PRL seric values were correlated with volume, sperm count,
      motility, viability, and morphology. The range of PRL levels (ng/mL) was 7.3 +/-
      2.1 in the control group (n = 46), 13.9 +/- 6.6 in asthenozoospermic (n = 51),
      12.6 +/- 7.8 in oligozoospermic (n = 42), and 10.9 +/- 4.8 in azoospermic
      patients (n = 28). Significantly higher (p < .0001) levels of PRL were found in
      the men with asthenozoospermia, oligozoospermia, and azoospermia. In the 121
      infertile patients with abnormal semen analysis, serum PRL levels were below 14.0
      ng/mL (normal mean + 3 SD) in 81 (66.9%) and above this level in 40 (33.1%)
      cases. Serum FSH and LH concentrations in azoospermic men were significantly
      higher (p < .0001) when compared with those of the control group, which indicates
      some disturbance of the spermatogenic process, and estradiol was significantly
      higher (p < .02) in oligozoospermic patients. No significant differences were
      found in serum testosterone. Twenty-one patients with idiopathic
      oligoasthenozoospermia and hyperprolactinemia were treated with 2.5 mg of
      bromocriptine daily for 6 months, resulting in a nonmeasurable effect on their
      sperm analysis. In conclusion, two-thirds of patients with oligozoospermia,
      asthenozoospermia, and azoospermia have normal PRL levels. Infertility in men due
      to moderate hyperprolactinemia could be associated with these sperm disturbances,
      but bromocriptine was of no therapeutic utility.

PMID- 9140617
TI  - Effect of short-term starvation on Leydig cell function in adult rats.
AB  - An experiment was carried out to analyze the effect of 3 days of starvation on
      the Leydig cell function in adult rats. Starvation markedly decreased plasma
      insulin and testosterone levels (p < .05). The weight of testes was maintained,
      whereas the testicular interstitial fluid volume decreased (p < .05). The level
      of testosterone decreased in this fluid (60%), whereas insulin levels showed no
      significant change. Purified Leydig cells showed normal LH/hCG binding in fasted
      rats but low insulin binding. The ability of these cells to produce testosterone
      in vitro was normal under both basal conditions and hCG stimulation in the
      absence and presence of insulin in the incubation medium. These data suggest that
      there is no gross impediment in the Leydig cell capacity to produce testosterone
      that might explain the starvation-associated decrease in plasma testosterone.

PMID- 9140618
TI  - Motility stimulant effects of prostasome inclusion in swim-up medium on
      cryopreserved human spermatozoa.
AB  - The chance of obtaining a fertilization and establishing a pregnancy increases
      with the number of motile spermatozoa that can reach and interact with the oocyte
      after the time of insemination. In an attempt to increase the recovery of freeze
      thawed and motile spermatozoa, the swim-up medium was supplemented with
      prostasomes and some other effectors. Swim-up media supplemented with prostasomes
      were superior in comparison to the other effectors investigated in the recovery
      of motile spermatozoa for insemination. These results suggest that prostasome
      inclusion in swim-up medium might be of benefit in improving results in assisted
      reproductive technologies using freeze-thawed spermatozoa.

PMID- 9140619
TI  - The use of iodixanol as a density gradient material for separating human sperm
      from semen.
AB  - Iodixanol, a new nonionic density gradient material with relatively low
      osmolality and high density, was evaluated to determine its suitability for the
      separation of human sperm from semen for their subsequent therapeutic use. Using
      a three-layer iodixanol gradient (approximately 1.17/1.15/1.05 g/mL), sperm were
      centrifuged at 1000g for 30 min and collected from the 1.05/1.15 interface. Using
      this method, a mean of 78% of the motile and 99% of the morphologically normal
      sperm originally present in the semen were recovered at the interface. There was
      no significant increase in the percentage of motile or morphologically normal
      sperm in the final preparation compared to the original semen. Sperm survived
      iodixanol density gradient centrifugation well, showing only modest declines in
      motility (18%) and velocity (35%) during a subsequent 24-h incubation period.
      When iodixanol was compared to Percoll density gradient centrifugation with semen
      from the same ejaculate, there was no significant difference between methods with
      regard to sperm yield, enrichment of motile or morphologically normal sperm in
      the preparation or sperm survival following separation. Iodixanol provides a
      suitable, nontoxic alternative to Percoll for the preparation of human sperm for
      therapeutic use.

PMID- 9140620
TI  - Inhibitors of collagen synthesis and hypophysectomy: effects on androgen induced
      growth of ventral prostate in rats.
AB  - To elucidate the effect of decreased amounts of collagen on prostatic growth,
      beta-aminopropionitrile, one of the agents that selectively inhibit collagen
      formation, was administered, with or without exogenous androgen and/or
      hypophysectomy, to rats of varying ages. The weight of the ventral prostate and
      the collagen content and the ratio of type III to type I collagen in the ventral
      prostate were examined. Administration of beta-aminopropionitrile, with or
      without exogenous androgen, reduced the collagen content in the ventral prostate
      in any age groups, but increased the weight of the ventral prostate only in young
      rats. Administration of beta-aminopropionitrile to hypophysectomized rats did not
      change the weight and collagen content. Administration of beta-aminopropionitrile
      prevented androgen-induced growth of prostatic collagen, resulting in increased
      prostatic weight in young rat. The ratio of type III to type I collagen in the
      rat ventral prostate remained unchanged by administration of beta
      aminopropionitrile, exogenous androgen, hypophysectomy, or advancing age. It
      would appear that in young rats prostatic collagen plays an important role in
      suppressing prostatic growth. The ratio of type III to type I collagen is stable
      under various experimental conditions in the ventral prostate.

PMID- 9140622
TI  - Should there be a clinical typology of posttraumatic stress disorder?
AB  - OBJECTIVE: The current classification of posttraumatic stress disorder in acute,
      chronic and delayed-onset types is incomplete and of limited usefulness. The
      present paper explores the possibilities of a clinically-based typology that
      would reflect both the patients' syndromic presentation and modern research
      findings. METHOD: Review of current clinical and research literature, with a
      critical examination of proposed typologies, parameters utilised, applicability
      and relevance; elaboration of theoretical and practical bases of a clinical
      typology of posttraumatic stress disorder. RESULTS: None of the existing
      posttraumatic stress disorder typologies presents a clinically comprehensive
      scope. A typology supported by literature findings and clinical observations is
      proposed. The six clinical types are depressive, dissociative, somatomorphic,
      psychotomorphic, organomorphic and 'neurotic-like'. Substance abuse and
      personality disorder-like variants remain as areas of investigation. CONCLUSIONS:
      The proposed typology, while accepting the nuclear manifestations of
      posttraumatic stress disorder, highlights prominent coexisting symptoms that
      define the clinical appearance of different patients. The typological approach in
      posttraumatic stress disorder does not carry the ambiguities of comorbidity, and
      facilitates a more specific and appropriate management of the cases.

PMID- 9140621
TI  - Effect of marginal or severe dietary zinc deficiency on testicular development
      and functions of the rat.
AB  - The effects of marginal (MZD) and severe (SZD) zinc-deficient diets on testicular
      function and development were studied in rats maintained on dietary treatment for
      6 weeks after weaning. SZD produced variable degrees of histological changes as
      compared with pair-fed controls, including a significant decrease in the diameter
      of seminiferous tubules (p < .05) with variable degree of maturation arrest in
      different stages of spermatogenesis. No significant histological changes were
      obtained in testes of MZD rats. MZD rats-exhibited significant decreases in serum
      levels of testosterone (62.6%, p < .001) and progesterone (18.2%, p < .05) with
      no changes in that of FSH or LH. SZD rats showed marked decreases in serum levels
      of testosterone (17.8-fold, p < .001) and progesterone (28.8%, p < .001), whereas
      FSH showed an increase (34.4%, p < .05) as compared with respective controls. In
      vitro acute stimulation by hCG on testicular tissue preparation obtained from MZD
      rats resulted in much less androgen production (sum of androstenedione,
      testosterone, and androstanediol) (72.4%, p < .001) as compared with controls.
      Testicular androgen contents (sum of androstenedione, testosterone, and
      androstanediol) decreased significantly in MZD and SZD rats, with the latter
      showing the greatest decrease. SZD rats were asospermic, whereas MZD rats
      exhibited marked decrease in sperm counts (by 22.9%, p < .05) as compared with
      respective controls. The results reflect a direct action of zinc deficiency on
      testicular steroidogenesis and strongly support the idea that hypogonadism of
      zinc deficiency results mainly from changes in testicular steroidogenesis or
      indirectly from Leydig cell failure.

PMID- 9140623
TI  - Psychiatry: an impossible profession?
AB  - OBJECTIVE: To examine the disconcerting question as to whether psychiatry is a
      fully-fledged profession or not. METHOD: A review of pertinent literature
      regarding the criteria of a profession, the vulnerability of psychiatry to abuse,
      and potential models for the proper practice of psychiatry. RESULTS: Psychiatry
      lost its professional anchorage entirely with its misuse to suppress dissent in
      the former Soviet Union and in the so-called euthanasia program in Nazi Germany.
      It remains vulnerable to abuse unless psychiatrists recognise the professional
      criteria they must satisfy. A new symbol, a humble stool, is proposed. Its, three
      legs represent the three equally significant dimensions of psychiatric practice:
      science, art and ethics. CONCLUSION: Psychiatry just 'scrapes home' in
      constituting a profession but only subject to three provisos:namely (i) that
      psychiatrists appreciate the need to achieve a coherent body of special knowledge
      through a genuine creative process which necessarily results in uncomfortable
      tension from time to time; (ii) that we promote the art of psychiatry by
      cultivating an ethos of caring and sensitivity; and (iii) that we function within
      an articulated ethical framework with respect for codes of ethics as guidelines.

PMID- 9140624
TI  - Psychiatric morbidity in Australian veterans of the United Nations peacekeeping
      force in Somalia.
AB  - OBJECTIVE: Since World War II, an increasing number of soldiers have been
      deployed in United Nations (UN) peacekeeping forces. However, little is known
      about the psychiatric impact of such deployments. The present study investigated
      the nature, prevalence, aetiology and natural history of psychiatric morbidity in
      Australian veterans of the United Nations peacekeeping force in Somalia. METHOD:
      Fifteen months after their return from Somalia, 117 Somalian veterans completed
      the 28-item version of the General Health Questionnaire (GHQ-28), the Impact of
      Events Scale (IES), the Combat Exposure Scale (CES), and a checklist of
      posttraumatic stress disorder symptoms, completed by veterans 12 months
      previously as part of an evaluation by the Department of Defence. Seventy-seven
      non-veteran controls also completed the GHQ-28. RESULTS: Veterans scored
      significantly higher on the GHQ-28 than controls. Twenty-four-point-eight per
      cent (24.8%) of veterans were GHQ cases (using 4/5 as a cut-off point) compared
      to 13.0% of controls. Psychiatric morbidity in veterans was associated with
      combat exposure and a past psychiatric history. Levels of morbidity reduced over
      time, although they remained substantial at 15 months following soldiers' return
      to Australia, with posttraumatic stress disorder symptoms being reported by
      approximately 20% of veterans. CONCLUSIONS: At least one-fifth of Australian
      soldiers who served in Somalia had significant levels of psychiatric morbidity 15
      months following their return. This was almost twice that of their non-veteran
      peers. Risk factors for the development of psychiatric morbidity included combat
      exposure and past psychiatric history. Levels of psychiatric morbidity were much
      higher than those reported in previous studies on UN soldiers.

PMID- 9140625
TI  - Child physical and sexual abuse and eating disorders: a review of the links and
      personal comments on the treatment process.
AB  - OBJECTIVE: The aim of the present paper is to review the available literature on
      abusive experiences and the development of eating disorders, with particular
      reference to the theoretical basis of the possible links between them. METHOD:
      The review covers the literature of both interpersonal violence and eating
      disorders, with special reference to that linking the two fields. Brief case
      reports and clinical experience from a specialised eating disorders unit are also
      described. RESULTS: Despite much theoretical speculation of a causal relation
      between abuse and eating dysfunction there is a lack of empirical research to
      confirm such theories, and a dearth of treatment suggestions to deal with the
      comorbid problems of the patient with an eating disorder and a history of abuse.
      CONCLUSIONS: There is a need for more clinical and experimental focus in this
      area, particularly in the study of aetiology and the management of dually
      affected individuals.

PMID- 9140626
TI  - Characteristics of childhood sexual abuse and adult psychopathology in female
      psychiatric patients.
AB  - OBJECTIVE: The present study investigated the relationship of characteristics of
      childhood sexual abuse and subsequent psychopathology. METHOD: Referrals to a
      female psychiatrist in private practice in an urban working class area provided
      73 adult female subjects who reported having been sexually abused in childhood.
      Data were collected on age at onset, duration, physical invasiveness of the
      abuse, violence, and the number and relationship of abusers. RESULTS: Having had
      multiple abusers in childhood was significantly (p < 0.01) associated with every
      outcome measure of severe psychopathology: an initial Global Assessment
      Functioning score of 50 or below; both single and repeated incidents of
      deliberate self-harm; overdose; self-mutilation; and psychiatric hospital
      admission. CONCLUSIONS: Notably, having had multiple abusers was the only
      characteristic showing a reliable independent association with any of these
      measures. Subjects who had had multiple abusers were significantly more likely to
      have an earlier age of onset and longer duration of abuse, and to have
      experienced violent abuse.

PMID- 9140627
TI  - Effects of childhood sexual abuse in adult female psychiatric patients.
AB  - OBJECTIVE: The present case-control study investigated the relationship between a
      history of childhood sexual abuse and subsequent psychopathology. METHODS:
      Referrals to a female psychiatrist in private practice in an urban working class
      area provided 73 adult female study subjects who reported having been sexually
      abused in childhood, and 73 randomly selected controls. RESULTS: Subjects had
      earlier onset of psychiatric disorders and higher incidence of deliberate self
      harm, rape in adulthood, and psychiatric hospitalisation. History of childhood
      sexual abuse had an effect independent of family psychiatric disorder. Although
      subjects and controls had a similar range of diagnoses, subjects were more likely
      to suffer anxiety disorders and controls more likely to suffer mood disorders.
      Controls were more likely to be prescribed antidepressants and subjects were more
      likely to receive supportive psychotherapy. Despite significantly lower initial
      Global Assessment of Functioning scores, subjects at completion of treatment had
      improved to the same scores as controls. CONCLUSION: The long-term effect of
      childhood sexual abuse is increased incidence of deliberate self-harm and is
      unrelated to any specific diagnosis. Despite more severe initial impairment,
      psychotherapy was effective for patients with a history of childhood sexual
      abuse.

PMID- 9140628
TI  - Psychiatric collaboration in a paediatric department.
AB  - OBJECTIVE: To review the impact of integrating child psychiatry services into a
      paediatric department. METHOD: Following the arrival of a new head of
      paediatrics, a mandatory multidisciplinary meeting was set up to review, diagnose
      and manage selected patients under the care of the paediatricians and/or a child
      psychiatrist. A prospective audit was undertaken of the patients discussed with a
      brief review of their outcome. The educational value of the meetings and their
      overall impact on the department was reviewed. RESULTS: Over an 8-month period 30
      patients were discussed in some detail with diagnoses ranging from a psychiatric
      disorder to a chronic organic illness, each subjected to the deliberations of the
      multidisciplinary team of the attending paediatrician, resident staff, child
      psychiatrist/psychologists, nurses, social worker, etc. Recommendations included
      further assessment by the psychiatric team, or management by the paediatricians
      with or without guidance of the former, involvement of an outside agency, etc.
      Such interventions generally had positive outcomes: at times dramatic, although
      early discharge often resulted in limited goals. There was also an overall
      increased awareness within the department of the psychological needs of the child
      and family and the importance of serious physical illness; this awareness is
      essential in the training of paediatricians and psychiatric staff. CONCLUSION:
      Closer integration of the two disciplines led to benefits both to the patients
      and staff. The initiation of a mandatory multidisciplinary meeting facilitated
      the process, overseen by a psychologically-minded new head of paediatrics. His
      departure led to a loss of some goals achieved, raising the question as to how
      such collaboration may be self-generating and ongoing. In addition, the issue of
      how to deal with those patients with ongoing difficulties not addressed during
      their limited inpatient stay was unresolved.

PMID- 9140629
TI  - Referred adolescents as young adults: the relationship between psychosocial
      functioning and personality disorder.
AB  - OBJECTIVE: To examine the functioning of young adults who had been referred for
      psychiatric treatment during adolescence. METHOD: A group of 145 adolescents
      referred at a mean age of 14 years were interviewed at a mean age of 20 years to
      ascertain their functioning and whether they suffered from a personality
      disorder. RESULTS: Having a personality disorder was associated with poor
      functioning at follow-up independently of adolescent diagnosis. Antisocial
      personalities were typified by problems with the law, a poor work record and
      early cohabitation, while other personality disorders were characterised by
      social isolation and problems in interpersonal relationships. Poor quality of the
      family environment and having received treatment during the follow-up period were
      the only developmental variables associated with poor functioning. CONCLUSIONS:
      Developing a personality disorder and having a poor family environment, rather
      than having an adolescent disorder, appear to be the factors that result in poor
      functioning in young adults.

PMID- 9140630
TI  - Family dynamics, hopelessness and psychiatric disturbance in parasuicidal
      adolescents.
AB  - OBJECTIVE: Adolescent parasuicide has often has been associated with family
      disturbance, hopelessness and psychiatric disturbance, but little empirical work
      has been done to verify these clinical impressions. METHOD: The present study
      compares matched groups of hospitalised parasuicidal adolescents, non-psychiatric
      medically hospitalised adolescents and a control group on measures of family
      disturbance, hopelessness and psychopathology. RESULTS: The findings reveal
      significantly higher levels of family disturbance, hopelessness and depressive
      symptoms in the parasuicidal group. CONCLUSIONS: The results suggest that
      prevention and treatment of adolescent parasuicide should focus on both
      individual and family dynamics.

PMID- 9140631
TI  - Depression in adults with intellectual disability. Part 1: A review.
AB  - OBJECTIVE: To examine the available literature regarding prevalence, clinical
      features and treatment of depression in adults with intellectual disability (ID).
      METHOD: A review of standard texts of ID and available literature examining
      psychiatric problems of individuals with ID. RESULTS: Few methodologically sound
      studies of prevalence have been reported. The clinical features of depression in
      adults with ID appear to vary with level of disability; in those with higher
      levels of disability in particular, irritability and anger, self-injurious and
      aggressive behaviour, psychomotor change and loss of activities of daily living
      skills may be observed rather than "classic' depressive symptoms. No systematic
      treatment studies have been reported; case reports support the efficacy of
      cognitive and behavioural strategies, antidepressants and electroconvulsive
      therapy. CONCLUSIONS: Well designed studies to assess the prevalence and evaluate
      the treatment of depression in individuals with ID are urgently needed. Design of
      these studies will need to address the questions of reliability and validity of
      diagnosis in individuals with ID and examine the appropriateness of available
      diagnostic criteria.

PMID- 9140632
TI  - Depression in adults with intellectual disability. Part 2: A pilot study.
AB  - OBJECTIVES: To identify adults with intellectual disability (ID) with a
      depressive disorder referred to a tertiary consultation clinic for psychiatric
      assessment; to investigate common presenting features of depression in adults
      with ID; to assess the utility of visual analogue scale (VAS) measures of
      emotion/behaviour, the CORE measure of psychomotor disturbance, and substitutive
      diagnostic criteria in the assessment of depressive disorders in this patient
      group. METHOD: Over a 6-month period 47 patients were seen for psychiatric
      evaluation. Patients in whom a diagnosis of depression was made were further
      assessed using: VAS measures of depression, irritability, verbal aggression,
      physical aggression, temper outbursts, regressed behaviour; CORE measure of
      psychomotor disturbance; and substitutive diagnostic criteria designed by the
      authors. RESULTS: Ten patients were found to have a depressive disorder.
      Substitutive criteria resulted in a greater rate of diagnosis than standard DSM
      IV criteria. The VAS measure of irritability was highly scored for all 10
      depressed patients. All 10 depressed patients were assigned to the melancholic
      subgroup according to CORE score. CONCLUSIONS: Standard assessment measures and
      diagnostic criteria may require modification to enhance their utility in this
      patient group. Melancholic features require further investigation.

PMID- 9140633
TI  - Ocular abnormalities in chronic schizophrenia: clinical implications.
AB  - OBJECTIVE: As part of a randomised double-blind study of a new atypical
      antipsychotic we sought to determine both the levels of visual acuity and the
      occurrence of toxic side-effects in a group of patients treated for many years on
      a variety of antipsychotics. METHODS: Twenty-three inpatients with a DSM-III-R
      diagnosis of chronic schizophrenia from two separate hospital locations who met
      the criteria for the double-blind trial were examined for ocular abnormalities at
      both baseline and at trial completion. RESULTS: At baseline a high prevalence of
      abnormalities was identified: 19 patients (82.6%) were found to have one or more
      ocular abnormalities, including lens opacities/cataracts and corneal
      pigmentation; three patients, with delusions related to the sun, were noted to
      have solar burns; a high proportion (almost 70%) of patients had untreated visual
      acuity problems. No further changes were observed at the follow-up examinations.
      CONCLUSIONS: The possible causes of ocular disturbance in schizophrenia and the
      reasons for the relatively high ocular morbidity in this group are thought to
      result from both illness-related factors and the effects of antipsychotic
      medication. Causality is confounded by a number of issues such as the high
      prevalence of smoking, poor general health and the variety of antipsychotic
      medications used in the treatment of psychosis as well as substance abuse. The
      clinical implications are considered in this paper in relation to the move
      towards community-based psychiatric services.

PMID- 9140635
TI  - Transcranial magnetic stimulation as therapy for depression and other disorders.
AB  - OBJECTIVE: To provide an overview of the progress and prospects of transcranial
      magnetic stimulation as a psychiatric therapy for depression. METHOD: Published
      and unpublished studies of the usefulness of transcranial magnetic stimulation as
      a therapy for depression were assessed, and characterised in terms of a
      consistent measure of dosage. Additional information was obtained through
      correspondence, personal meetings and visits to facilities. RESULTS: Transcranial
      magnetic stimulation, a means for inducing small regional currents in the brain,
      has been used in clinical neurology for some time, and can be used on conscious
      subjects with minimal side-effects. Early researchers noticed transient mood
      effects on people receiving this treatment, which prompted several inconclusive
      investigations of its effects on depressed patients. More recently, knowledge of
      functional abnormalities associated with depression has led to trials using
      repetitive transcranial magnetic stimulation to stimulate underactive left
      prefrontal regions, an approach which has produced short-term benefits for some
      subjects. The higher dosage delivered by high-frequency repetitive transcranial
      magnetic stimulation appears to produce greater benefits; scope exists for more
      conclusive studies based on extended treatment periods. CONCLUSIONS: Repetitive
      transcranial magnetic stimulation is a promising technology. The reviewed
      evidence indicates that it may be useful in the treatment of depression, and
      perhaps other disorders which are associated with regional hypometabolism. Should
      repetitive transcranial magnetic stimulation prove an effective, non-invasive,
      drug-free treatment for depression, a range of disorders could be similarly
      treatable.

PMID- 9140634
TI  - The assessment of clinically significant change using the Life Skills Profile.
AB  - OBJECTIVE: In the context of the need to develop practical outcome measures, the
      present study aimed to assess the sensitivity of the Life Skills Profile (LSP) in
      terms of differences between hospital-based and community-based clients, and to
      assess the sensitivity of the LSP to changes over time. In this way, criteria
      could be established whereby the LSP could be used to determine appropriate
      changes in locus of care, both in terms of the "cut-off' for hospital-based and
      community-based tenure, and the level of "clinically significant change' in
      functioning. METHOD: The LSP was administered at 3-monthly intervals to 200
      clients of an area public mental health service with serious mental illness over
      a 21-month period. Locus of care (hospital or community) was noted at each
      administration. RESULTS: Clients in the community scored significantly better
      than those in hospital, however there was a great deal of overlap. Using hospital
      or community tenure as the variable of interest, a measure of reliable and
      clinically significant change over a 3-month period based on the LSP was
      developed. A total LSP score of 116.5 or above best discriminated clients in the
      community from those in hospital, and a difference of 18 points or more in two
      LSP obtained 3 months apart was unlikely to have arisen by chance. A simple, two
      part criterion of significant change based on these results showed 89% accuracy
      in matching transition (or lack of transition) between hospital and community
      with changes in LSP scores. CONCLUSIONS: The results need to be understood within
      the methodological limitations of the present study. The findings provide users
      of the LSP with guidelines for the interpretation of repeat assessments. This may
      encourage more services to use formal reassessment methods to monitor the
      progress of their clients.

PMID- 9140636
TI  - Intravenous sedation of involuntary psychiatric patients in New South Wales.
AB  - OBJECTIVE: Intravenous sedation of involuntary psychiatric patients is practised
      in almost all hospitals in New South Wales. Despite its widespread use, little
      has been published about the medications used or their safety and efficacy. The
      present study reports the frequency and reasons for intravenous sedation, the
      medications used, and the incidence of adverse effects. METHOD: Eighteen of 21
      acute psychiatric admission units in the State were reviewed. The medical records
      of a random sample of 495 patients admitted involuntarily during 1990 were
      examined and information from the progress notes, drug charts and physical
      observations was recorded and subjected to statistical analysis. RESULTS: Of the
      495 patients, 132 (27%) were intravenously sedated. Eighty-six percent (86%) of
      patients received a combination of haloperidol or diazepam, usually 20 mg of each
      drug. The threat of violence was the most significant patient characteristic
      predicting the use of intravenous sedation. Patients with mania or intoxication
      were relatively more likely to be intravenously sedated than other diagnostic
      categories. Patients admitted via accident and emergency departments and those
      admitted to teaching and metropolitan general hospitals compared to rural and
      large psychiatric hospitals were significantly more likely to receive intravenous
      sedation. The most common complications of intravenous sedation were dystonia
      (37%), hypotension (8%) and confusion (5%). The incidence of phlebitis and other
      extrapyramidal side-effects was probably under-reported. CONCLUSION: About one in
      four involuntary psychiatric patients receive intravenous sedation in NSW.
      Intravenous sedation is more likely when patients are admitted through accident
      and emergency departments to teaching or metropolitan hospitals, and pose a
      threat of violence. Intravenous sedation was shown to be a safe procedure given
      certain precautions.

PMID- 9140637
TI  - Seasonal affective disorder in Australia: is photoperiod critical?
AB  - OBJECTIVES: Seasonal affective disorder (SAD) is a variant of recurrent
      depression in which episodes are linked to a particular season, typically winter.
      SAD is understood as the extreme end of a continuum of seasonality in the general
      population. Photoperiod (the timing and duration of daylight) has been assumed to
      be aetiologically critical. The present research used a survey design to
      investigate the assumed centrality of photoperiod for SAD/seasonality in
      Australia. Two hypotheses were tested: that self-reported seasonality does not
      increase further from the equator and that seasonality does not stand alone from
      non-seasonal neurotic complaints. METHOD: The sampling frame used was adult
      females on the Australian Twin Registry roll. A sample of 526 women residing
      across the latitudes of Australia responded to a survey based around the Seasonal
      Pattern Assessment Questionnaire (SPAQ). The SPAQ asks respondents to
      retrospectively report on season-related changes in mood and behaviour. The
      survey also contained three questionnaire measures of neurotic symptoms of
      anxiety and depression: the General Health Questionnaire (GHQ), the Community
      Epidemiological Survey for Depression (CES-D) and the State-Trait Anxiety
      Inventory-Trait (STAI-T). RESULTS: Self-reported seasonality did not correlated
      with latitude (r = 0.01, NS). On the other hand, a substantial relationship was
      found between seasonality and each of the measures of non-seasonal complaints:
      GHQ (r = 0.35, p < 0.001); CES-D (r = 0.35, p < 0.001); and STAI-T (r = 0.30, p <
      0.001). CONCLUSIONS: Within the limitations of a design based on retrospective
      self-report, the findings of the present study suggest that the diathesis for
      SAD/seasonality may not be photoperiod-specific. At least in Australia, there is
      provisional support for the proposal that human seasonality may have a broader
      psychological component. The findings are discussed in terms of established
      research into normal mood, trait personality and non-seasonal depression.

PMID- 9140639
TI  - Inpatient suicides in an Australian mental hospital.
AB  - OBJECTIVE: Suicide rates among psychiatric inpatients are higher than in the
      general population. Mental health professionals are poor at predicting suicide
      risk. METHOD: One hundred and three inpatient suicides, over a 21-year period, in
      a large psychiatric hospital in Melbourne were examined. The characteristics,
      including demographic and clinical data, for 60 of these suicides were compared
      with a matched comparison group stratified for the time of admission. Violent
      methods (including jumping in front of trains, trams and road traffic, jumping
      off buildings, hanging and drowning) were most frequently used. RESULTS: Over one
      third of the suicides occurred during periods of approved leave and a similar
      number occurred after absconding from the hospital. Suicide was associated with a
      diagnosis of schizophrenia, increased duration of admission, more frequent
      prescription of neuroleptics and antidepressants, previous deliberate self-harm,
      suicidal ideation at the time of admission and during the admission, suicide
      attempts during the admission, unstable (fluctuating) suicidal ideation during
      the admission and a greater number of ward transfers. CONCLUSIONS: Psychiatric
      units should be developed away from readily available methods of suicide.
      Patients with previous or intra-admission suicidal ideation or attempts, or
      unstable suicidal ideation, should be carefully observed to avoid absconding.
      Suicide risk should be carefully evaluated in such patients prior to approving
      periods of leave.

PMID- 9140638
TI  - Sexually transmitted disease and family planning counselling of psychiatric
      patients in New Zealand.
AB  - OBJECTIVE: We aimed to determine the attitudes and behaviours of mental health
      professionals (MHPs) including psychiatrists towards identifying and reducing
      their own patients' risk for sexually transmitted diseases and unwanted
      pregnancies. METHOD: 102 of all of the 162 mental health professionals serving
      predominantly chronically psychiatrically ill adult outpatients and inpatients in
      Waitemata district responded to an anonymous questionnaire (response rate = 63%),
      concerning their own attitudes and behaviours towards identifying and counselling
      patients on their risk for sexually transmitted diseases and unwanted
      pregnancies. RESULTS: Mental health professionals reported that, on average, they
      had counselled 14% of their own male patients and 21% of their own female
      patients on sexually transmitted diseases, including AIDS prevention, and that
      more of their own patients were at risk than were counselled. They also reported
      that they had counselled 5% of their own male patients and 17% of their own
      female patients about family planing. Forty-two per cent of mental health
      professionals indicated that they had insufficient knowledge about sexually
      transmitted diseases to educate patients, 72% indicated that when it came to
      risky sexual behaviours chronic psychiatric patients were much the same as other
      people, and 33% or more felt uncomfortable discussing topics of condom use and
      patients' sexual preferences. CONCLUSION: These results suggest that family
      planning and sexually transmitted diseases risk preventive interventions for
      psychiatric patients need to overcome mental health professionals' own barriers
      to risk prevention.

PMID- 9140640
TI  - Is there an adult form of separation anxiety disorder? A brief clinical report.
AB  - OBJECTIVE: The aim of this clinical report is to investigate whether symptoms of
      separation anxiety disorder can occur in adulthood. CLINICAL PICTURE: Three cases
      are described to illustrate that adults may experience: wide-ranging separation
      anxiety symptoms, such as extreme anxiety and fear, when separated from major
      attachment figures; avoidance of being alone; and fears that harm will befall
      those close to them. Symptoms of panic appeared to be secondary to separation
      anxiety, and none of the patients fulfilled criteria for dependent personality
      disorder. TREATMENT: Group cognitive behavioural treatment focusing on preventing
      panic attacks and generalised anxiety did not appear to have an impact on core
      separation anxiety symptoms. OUTCOME: Exacerbations of separation anxiety
      appeared to be closely linked to actual or threatened ruptures to primary bonds.
      CONCLUSIONS: Separation anxiety disorder may be a neglected diagnosis in
      adulthood. Formal nosological systems such as the DSM may need to be revised to
      incorporate adult manifestations of the disorder.

PMID- 9140641
TI  - Cannabis-induced chronic psychosis: an underacknowledged disorder?

PMID- 9140642
TI  - Separate adolescent psychiatry?

PMID- 9140643
TI  - SSRI antidepressants and SIADH.

PMID- 9140644
TI  - Comment on "the fishing news'.

PMID- 9140645
TI  - Season of birth and schizophrenia: southern hemisphere data.

PMID- 9140646
TI  - Treatment of rupture of suspensory ligament and superficial flexor tendon in a
      bull.
AB  - Rupture of the suspensory ligament at the insertions on the proximal sesamoid
      bones, and of the superficial flexor tendon of the left fore limb, occurred in an
      adult Angus bull as a result of fighting. There was severe hyperextension of the
      metacarpophalangeal (MCP) joint with the dewclaws almost touching the ground.
      Radiographs revealed severe hyperextension of the MCP joint with the sesamoid
      bones aligned directly distal to the metacarpus. Initially, a full length
      fiberglass cast was applied with the limb partially flexed within the cast and
      the heels elevated. The cast was replaced twice. The cast was removed after 136
      days and the bull was bearing full weight on the limb. Prolonged immobilisation
      of the limb produced new bone in the area (a normal response in cattle) to cause
      ankylosis of the traumatized MCP joint and partial ankylosis of the carpus. The
      bull was being used for pasture breeding one year after the injury.

PMID- 9140647
TI  - Concurrent gout and suspected hypovitaminosis A in crocodile hatchlings.

PMID- 9140648
TI  - Tick paralysis and hepatic lipidosis in a llama.

PMID- 9140649
TI  - Tendonitis of the branches of insertion of the superficial digital flexor tendon
      in horses.
AB  - OBJECTIVE: To describe clinical findings, ultrasonographic features and outcome
      of injury to the branches of insertion of the superficial digital flexor (SDF)
      tendon in horses. DESIGN: Retrospective study of 14 cases. PROCEDURE: Fourteen
      Thoroughbred horses with tendonitis affecting the branches of insertion of the
      SDF tendon were examined for lameness, location and amount of swelling, and the
      presence of other musculoskeletal abnormalities. The flexor tendons were assessed
      by ultrasonographic examination, and recommendations were made for management of
      the cases. Outcome was assessed by re-examination of some horses, direct
      communication with the owner or trainer, and examination of race records.
      RESULTS: The lateral SDF branch was affected in 10 horses; the medial branch in
      three, and both branches in one horse. Two horses had concurrent injuries to the
      SDF tendon in the metacarpal region of the contralateral limb. Ultrasonographic
      findings included swelling of the affected SDF branch, peritendinous fluid
      accumulation, disruption of normal fibre alignment on sagittal scan, and variable
      loss of echogenicity. As healing occurred, there was return of normal
      echogenicity, but normal fibre alignment did not return completely and apparent
      adhesions formed between the affected SDF branch and adjacent structures. Seven
      of 10 horses which returned to their previous use were able to compete without
      further tendon injury. Recurrence of injury occurred in one case, and another two
      horses developed tendonitis in the metacarpal region. One horse was retired from
      racing but was able to compete at dressage without recurrence of injury. Two
      horses were retired for breeding without returning to training, and one horse was
      sold and lost to follow up but did not race. CONCLUSION: The prognosis is fair
      for return to previous use following injury to the branches of insertion of the
      SDF tendon in athletic horses.

PMID- 9140650
TI  - Foetal anasarca in Awassi sheep.
AB  - Two anasarcous foetuses of Awassi sheep are described. The foetuses were removed
      from the dams by caesarean section because of dystocia due to failure of cervical
      dilation. Uterine incision was made in situ because uteri were so distended they
      could not be brought out from the site of incision. Large quantities of uterine
      fluids and abnormal thick placentas were found. One foetus weighed about 7 kg and
      the other 13 kg. The foetal heads were deformed: the upper jaw was prognathic and
      the left ear of the small foetus was cystic. Necropsy revealed subcutaneous
      musculature was soft and flabby and abdominal and thoracic cavities contained
      serosanguinous fluid. Histopathological examination revealed that only the larger
      foetus had focal aggregates of basophilic nucleated red blood cells and scattered
      megakaryocytes in the liver. We conclude that anasarca can occur in Awassi sheep,
      with and without associated extramedullary haematopoiesis.

PMID- 9140651
TI  - Modes of treatment.

PMID- 9140652
TI  - A case-control study to identify farm factors affecting fertility of dairy herds:
      multivariate description of factors.
AB  - OBJECTIVES: To determine whether a multivariate model could be developed to
      describe farm factors affecting fertility of dairy herd and to examine the
      factors that determined better reproductive performance on dairy farms in New
      South Wales. PROCEDURE: We examined the results of a survey of breeding
      practices, mating policies, recording systems, timing of mating, heat detection,
      treatment of metritis and manager demographics of dairy farms using Principal
      components analysis, logistic regression and the sign test. RESULTS: Eight
      principal components for heat detection computed using Principal component
      analyses were included in the multivariate model to reflect primary and secondary
      heat detection signs used in the breeding decisions of managers. A final model
      identified three variables: optimum number of days to first service, number of
      people detecting heats, and age of manager which significantly influenced the
      risk of being in the high or low reproductive performance groups. A failure to
      breed at an appropriate time after calving and having more people responsible for
      heat detection was associated with herds with a prolonged intercalving interval.
      While the model provided a good fit for the data, it was not highly
      discriminatory. Examination of 83 management practices affecting fertility using
      the sign test (P = 0.01) indicated that managers of herds with good reproductive
      performance employed better management and breeding practices more often than
      managers of herds with poor reproductive performance. CONCLUSIONS: Mating cows
      sooner after calving and using fewer people to detect oestrus should reduce
      calving to conception intervals. Veterinarians investigating herd reproductive
      performance should consider the potential for a number of subtle failures of
      management to significantly impair fertility rather than limit investigations to
      a few factors.

PMID- 9140654
TI  - Epidemiological studies of pig diseases: 1. Use of French protocols for risk
      factor assessment to predict the health status of Australian herds.
AB  - OBJECTIVE: To determine in Australian pig herds the accuracy of French protocols
      for risk factor assessment. PROCEDURE: Data on health indicators and risk factors
      were collected for three syndromes, 'pre-weaning diarrhoea', 'post-weaning
      diarrhoea' and 'respiratory problems', using the French protocols. The protocols
      were used on 118 occasions in 32 Western Australian pig herds during 3 years
      (1988 to 1991). RESULTS: There was a wide variation in pre-weaning performance,
      for example growth rate was 107 to 273 g/day (< 200 g/day in 33% of herds).
      Respiratory lesions at weaning were associated with poor pre-weaning performance.
      Post-weaning (21 days after weaning) growth rate was 114 to 408 g/day (< 250
      g/day in 54% of herds). In the grower herds, 91% of herds had pneumonia, and
      growth rate was 439 to 625 g/day (< 550 g/day in 54% of herds). Pleurisy as well
      as pneumonia was associated with reduced growth rate. The risk factor most
      closely associated with respiratory health status was air volume per pig.
      CONCLUSION: Risk factors were most accurate at predicting the health status in
      post-weaning problems. A weaning weight of at least 7.9 kg and weaning age of 30
      days optimised weaner performance. Stocking densities and shed designs providing
      at least 3 m3 air volume and 0.6 m2 floor space per pig throughout the growing
      phase should be considered for an improved respiratory health status. Australian
      pig sheds often do not provide a satisfactory environment for optimum health. The
      technique of risk factor assessment as an aid to the maintenance of health in pig
      herds is applicable in Australia, but further research is necessary to determine
      the most important Australian risk factors.

PMID- 9140653
TI  - A case-control study to identify farm factors affecting fertility of dairy herds:
      univariate description of factors.
AB  - OBJECTIVE: To identify farm factors which were associated with reproductive
      performance in dairy herds in New South Wales. PROCEDURE: A survey was
      administered by face to face interview to examine the responses of producers
      drawn from 757 herds, which used the New South Wales Agriculture Department Dairy
      Herd Improvement scheme. A case-control approach was used to select a total of
      126 herds from the first (top group-cases) and fourth quartiles (low group
      controls) for intercalving interval. RESULTS: We found that the estimated
      interval from calving to first mating was significantly different between group
      (P = 0.03) and that the groups significantly differed in both their target for
      interval to first mating (P = 0.02) and their perceived optimum time for first
      mating (P = 0.04). Other factors associated with a longer intercalving interval
      included, use of embryo transfer programs (P = 0.08), younger managers (P =
      0.02), fewer breedings per day (P = 0.01), a greater number of people detecting
      heats (P = 0.07), but less hours spent detecting heats while handling the cows (P
      = 0.11), and a failure to vaccinate bulls for campylobacteriosis (P = 0.14).
      CONCLUSIONS: Managers of herds with poorer reproductive performance did not
      intend to mate cattle as soon after calving as managers with better reproductive
      performance, were not as active in seeking veterinary advice on reproduction, and
      were attempting to treat reproductive diseases and disorders themselves.

PMID- 9140655
TI  - Epidemiological studies of pig diseases: 2. Post-weaning diarrhoea and
      performance in Western Australian pigs.
AB  - OBJECTIVE: To determine in Australian pig herds the accuracy of French protocols
      for risk factor assessment of post-weaning diarrhoea and illthrift. PROCEDURE:
      French protocols for the collection of data on health indicators and risk factors
      for post-weaning diarrhoea were conducted on 54 batches of weaner pigs from 28
      Western Australian pig herds during three years. RESULTS: Large variations in
      post-weaning performance were found. About one-third of the batches were growing
      at < 200 g/day during the 3 weeks after weaning, and 54% had growth rates of <
      250 g/day. Weaning age and weight of at least 30 days and 7.9 kg, respectively,
      optimised weaner performance. Other risk factors associated with little post
      weaning diarrhoea and good weaner performance were high creep feed intakes,
      relatively little diarrhoea as suckers, and, contrary to expectations, large
      temperature fluctuations. CONCLUSION: Overall, the 'predictability' of post
      weaning problems as assessed by measurement of risk status, was good. However,
      the model was less accurate at predicting the performance of a single batch of
      pigs.

PMID- 9140656
TI  - Identification and characterisation of an H7N3 influenza A virus from an outbreak
      of virulent avian influenza in Victoria.

PMID- 9140657
TI  - Verotoxin-producing Escherichia coli from the faeces of sheep, calves and pigs.

PMID- 9140658
TI  - Effect of a single bout of high intensity exercise on lower respiratory tract
      contamination in the horse.

PMID- 9140659
TI  - Effects of weak microwave fields amplitude modulated at ELF on EEG of symmetric
      brain areas in rats.
AB  - Averaged electroencephalogram (EEG) frequency spectra were studied in eight
      unanesthetized and unmyorelaxed adult male rats with chronically implanted carbon
      electrodes in symmetrical somesthetic areas when a weak (0.1-0.2 mW/cm) microwave
      (MW, 945 MHz) field, amplitude-modulated at extremely low frequency (ELF) (4 Hz),
      was applied. Intermittent (1 min "On," 1 min "Off") field exposure (10-min
      duration) was used. Hemispheric asymmetry in frequency spectra (averaged data for
      10 or 1 min) of an ongoing EEG was characterized by a power decrease in the 1.5-3
      Hz range on the left hemisphere and by a power decrease in the 10-14 and 20-30 Hz
      ranges on the right hemisphere. No differences between control and exposure
      experiments were shown under these routines of data averaging. Significant
      elevations of EEG asymmetry in 10-14 Hz range were observed during the first 20 s
      after four from five onsets of the MW field, when averaged spectra were obtained
      for every 10 s. Under neither control nor pre- and postexposure conditions was
      this effect observed. These results are discussed with respect to interaction of
      MW fields with the EEG generators.

PMID- 9140660
TI  - ELF magnetic field exposure system with feedback-controlled disturbance
      rejection.
AB  - Extremely low-frequency (ELF) magnetic field exposure systems are usually subject
      to field disturbances induced by external sources. Here, a method for designing a
      feedback control system for cancelling the effect of external ELF magnetic field
      disturbances on the magnetic field over the exposure area is presented. This
      method was used in the design of a feedback-controlled exposure system for an
      inverted microscope stage. The effectiveness of the proposed feedback control
      system for disturbance rejection was verified experimentally and by means of
      computer simulation.

PMID- 9140661
TI  - Study of magnetic fields from power-frequency current on water lines.
AB  - The magnetic fields from power-frequency current flowing on water lines were
      investigated in a new approach that involved an area-wide survey in a small town.
      Magnetic fields were measured outside the residence under power cables and over
      water lines, and each residence was characterized as to whether it received water
      from a private well or the municipal water system. The magnetic field data
      revealed two statistical modes when they were related to water supply type. The
      data also showed that in the case of the high mode, the magnetic field remained
      constant along the line formed by power drop wires, at the back of the house, and
      the water hookup service, in front of the house, all the way to the street. The
      patterns are explained by the coincidence of measurement points and the presence
      of net current flowing on power mains, power drop conductors, residential
      plumbing, water service hookups, and water mains. These patterns, together with
      other characteristics of this magnetic field source, such as the gradual spatial
      fall-off of this field and the presence of a constant component in the time
      sequence, portray a magnetic field more uniform and constant in the residential
      environment than has been thought to exist. Such characteristics make up for the
      weakness of the source and make net current a significant source of exposure in
      the lives of individuals around the house, when human exposure to magnetic fields
      is assumed to be a cumulative effect over time. This, together with the bimodal
      statistical distribution of the residential magnetic field (related to water
      supply type), presents opportunities for retrospective epidemiological analysis.
      Water line type and its ability to conduct power-frequency current can be used as
      the historical marker for a bimodal exposure inference, as Wertheimer et al. have
      shown.

PMID- 9140662
TI  - Comparison of cardiac and 60 Hz magnetically induced electric fields measured in
      anesthetized rats.
AB  - Extremely low frequency magnetic fields interact with an animal by inducing
      internal electric fields, which are in addition to the normal endogenous fields
      present in living animals. Male rats weighing about 560 g each were anesthetized
      with ketamine and xylazine. Small incisions were made in the ventral body wall at
      the chest and upper abdomen to position a miniature probe for measuring internal
      electric fields. The calibration constant for the probe size was 5.7 mm, with a
      flat response from at least 12 Hz to 20 kHz. A cardiac signal, similar to the
      normal electrocardiogram with a heart rate of about 250 bpm, was readily obtained
      at the chest. Upon analysis of its spectrum, the cardiac field detected by the
      probe had a broad maximum at 32-95 Hz. When the rats were exposed to a 1 mT, 60
      Hz magnetic field, a spike appeared in the spectrum at 60 Hz. The peak-to-peak
      magnitudes of electric fields associated with normal heart function were
      comparable to fields induced by a 1 mT magnetic field at 60 Hz for those
      positions measured on the body surface (where induced fields were maximal).
      Within the body, or in different directions relative to the applied field, the
      induced fields were reduced (reaching zero at the center of the animal). The
      cardiac field increased near the heart, becoming much larger than the induced
      field. Thus, the cardiac electric field, together with the other endogenous
      fields, combine with induced electric fields and help to provide reference levels
      for the induced-field dosimetry of ELF magnetic field exposures of living
      animals.

PMID- 9140663
TI  - Search for frequency-specific effects of millimeter-wave radiation on isolated
      nerve function.
AB  - Effects of a short-term exposure to millimeter waves (CW, 40-52 GHz, 0.24-3.0
      mW/cm2) on the compound action potential (CAP) conduction were studied in an
      isolated frog sciatic nerve preparation. CAPs were evoked by either a low-rate or
      a high-rate electrical stimulation of the nerve (4 and 20 paired pulses/s,
      respectively). The low-rate stimulation did not alter the functional state of the
      nerve, and the amplitude, latency, and peak latency of CAPs could stay virtually
      stable for hours. Microwave irradiation for 10-60 min at 0.24-1.5 mW/cm2, either
      at various constant frequencies or with a stepwise frequency change (0.1 or 0.01
      GHz/min), did not cause any detectable changes in CAP conduction or nerve
      refractoriness. The effect observed under irradiation at a higher field intensity
      of 2-3 mW/cm2 was a subtle and transient reduction of CAP latency and peak
      latency along with a rise of the test CAP amplitude. These changes could be
      evoked by any tested frequency of the radiation; they reversed shortly after
      cessation of exposure and were both qualitatively and quantitatively similar to
      the effect of conventional heating of 0.3-0.4 degree C. The high-rate electrical
      stimulation caused gradual and reversible decrease of the amplitude of
      conditioning and test CAPs and increased their latencies and peak latencies.
      These changes were essentially the same with and without irradiation (2.0-2.7 or
      0.24-0.28 mW/cm2), except for attenuation of the decrease of the test CAP
      amplitude. This effect was observed at both field intensities, but was
      statistically significant only for certain frequencies of the radiation. Within
      the studied limits, this effect appeared to be dependent on the frequency rather
      than on the intensity of the radiation, but this observation requires additional
      experimental confirmation.

PMID- 9140664
TI  - Body heating induced by sub-resonant (350 MHz) microwave irradiation:
      cardiovascular and respiratory responses in anesthetized rats.
AB  - These experiments were designed to investigate the effects of sub-resonant
      microwave (MW) exposure (350 MHz, E orientation, average power density 38 mW/cm2,
      average whole-body specific absorption rate 13.2 W/kg) on selected physiological
      parameters. The increase in peripheral body temperature during 350 MHz exposure
      was greater than that in earlier experiments performed at 700 MHz (resonance).
      Heart rate and mean arterial blood pressure were significantly elevated during a
      1 degree C increase in colonic temperature due to 350 MHz exposure; respiratory
      rate showed no significant change. The results are consistent with other
      investigators' reports comparing sub-resonance exposures with those at resonance
      and above.

PMID- 9140665
TI  - Interactions between sleep, other body rhythms, immune responses, and exercise.
AB  - Biological rhythms can influence both exercise tolerance and immune function.
      Most studies have focussed upon circadian rhythms, but some circaseptan,
      circatrigintan, and circannual cycles have also been described. Rhythms may have
      an endogenous or an exogenous basis. Endogenous rhythms originate in the cells of
      the suprachiasmatic nucleus. Impulses from this region pass to the pineal gland,
      where they regulate the production of melatonin, a compound that modulates the
      sleep/wakefulness cycle. Endocrine, physiological, and psychological parameters
      all show evidence of periodicity. Most components of the immune system, both
      cellular and humoral, also show large rhythmic changes. It is not yet clear how
      far such periodicity is secondary to changes in other body systems. Nevertheless,
      the magnitude of variation is such that it is vital to obtain experimental and
      control data at identical time points in both acute and chronic studies of
      exercise and immune function. Disturbance of the sleep/wakefulness cycle can
      constitute a form of stress, with adverse consequence for immune function.

PMID- 9140666
TI  - The influence of musculotendinous stiffness on drop jump performance.
AB  - This study investigated the relationship between musculotendinous stiffness and
      the ability to perform dynamic stretch-shorten cycle actions involving a range of
      eccentric loads. Twenty trained male subjects performed a series of quasi-static
      muscular actions in a supine leg press position, during which a brief
      perturbation was applied. The resulting damped oscillations allowed the
      estimation of each subject's maximal musculotendinous stiffness (k) for the lower
      body musculature. All subjects also performed a countermovement jump (CMJ) and a
      series of drop jumps (DJs) from heights of 20, 40, 60, 80, and 100 cm. When the
      jump heights of the nine most compliant (mean k = 11.4 +/- 2.7 kNxm-1) and nine
      stiffest (mean k = 20.5 +/- 2.5 kNxm-1) subjects were compared the stiff subjects
      demonstrated significantly poorer capacity to perform under the highest (DJ80 and
      DJ100) eccentric loading conditions. It was hypothesised that the relatively
      greater forces transmitted from the skeletal system to the musculature of the
      stiff subjects reduced their ability to attenuate the higher eccentric loads due
      to less effective contractile dynamics and greater levels of reflex induced
      inhibition.

PMID- 9140667
TI  - Circulating levels of peripheral blood leucocytes and cytokines following
      competitive cycling.
AB  - The objective of the study was to determine if prolonged and strenuous cycling
      leads to a polarized cytokine response, and/or unique mobilization of circulating
      leucocyte populations. Resting venous blood samples were collected from 6 amateur
      cyclists, 24 hr before, and at 10-25 min and 150 min after completion of a 250-km
      road race (race time: 404 +/- 3.5 min). Total leucocyte counts were significantly
      elevated following competition. Cell counts of CD3+CD8bright+ lymphocytes were
      depressed by 50% 150 min after competition. A significant increase in CD4+ cells
      expressing the IL-2R alpha chain was evident 150 min after competition. IL-6
      concentrations were greatly increased, both at 10-25 min and 150 min after
      competition. Resting TNF-a concentrations were approximately doubled at both time
      points after competition. Plasma levels of IFN-gamma, IL-10 and IL-12 were below
      detection thresholds at all time points. These results suggest that performance
      of a 6.5 h competitive cycle-race does not induce a Type-1 or Type-2-dominated
      cytokine response, but one that is typical of a proinflammatory cytokine
      response.

PMID- 9140668
TI  - The effect of eumenorrheic menstrual cycle phase on physiological responses to a
      repeated lifting task.
AB  - Cyclic variations in physiological and endocrinological baselines are known to be
      consistent with the eumenorrheic (healthy) menstrual cycle. The aim of this study
      was to examine the interaction of these variations with the physiological
      responses to repeated lifting. Sixteen females visited the laboratory in each of
      five phases of their menstrual cycle. During each visit, subjects performed a
      repetitive lifting task, lifting a weighted box, from knee to shoulder height, at
      six repetitions per minute for 10 min. Oxygen consumption, minute ventilation,
      heart rate (HR), and perceived exertion were monitored throughout the task. The
      variation in physiological and subjective responses to lifting with menstrual
      cycle phase did not reach statistical significance (p > .05). However, the HR
      response to lifting was elevated by approximately 10 beats x min-1 in the
      postovulatory phases of the cycle (effect size > 0.61). Although the impact of
      the menstrual cycle upon lifting performance is minimal, alterations in HR must
      be taken into account in determining new international standards for manual
      handling.

PMID- 9140669
TI  - Comparison of sweat rate measured by a pouch collector and a hygrometric
      technique during exercise.
AB  - Measurements of local sweat rate (back) determined with a closed-pouch collector
      made of polyethylene (110 cm2) were compared with those obtained from a
      ventilated capsule using an infrared photometric hygrometer technique. Eight
      young male subjects underwent three exercise sessions each for 60 min at 45%
      VO2max on a cycle ergometer at an ambient temperature of 35 degrees C and 35%
      relative humidity. When the onset and transient sweating periods (0-20 min) are
      excluded from calculations, the difference between the mean values obtained by
      the collector and the sweat capsule during the 20-60 time period is only 0.06 +/-
      0.04 mg x cm-2 x min-1 (5%). Although a significant correlation (r = .74, p <
      .05) was obtained between methods, individual differences in sweat-rate
      measurements varied on average +/-0.22 mg x cm-2 x min-1 (+/-19%). Designed more
      specifically for sweat-content analysis, the pouch collector may serve as a
      satisfactory field method to approximate the local sweat rate and excretion
      induced by prolonged exercise in a hot environment.

PMID- 9140670
TI  - Recovery of left ventricular function following early reperfusion in acute
      myocardial infarction: a potential role for the calcium antagonist nisoldipine.
AB  - The purpose of the present study was to test whether the administration of a
      vascular-selective organic calcium antagonist (nisoldipine) at the onset of early
      mechanical reperfusion (by coronary angioplasty) in acute myocardial infarction
      could prevent or attenuate postischemic stunning and enhance the recovery of left
      ventricular function in these patients. The study included 36 patients with
      anterior acute myocardial infarction who underwent an early and successful
      primary coronary angioplasty within 3 hours of the onset of chest pain (mean time
      to reperfusion = 113 +/- 37 minutes). The infarct-related artery was the left
      anterior descending artery in all patients. All had single-vessel disease.
      Baseline coronary arteriography was completed by left ventriculography. When the
      infarct-related artery was identified, a guidewire was placed into the target
      vessel and a balloon catheter was positioned in the artery. At this point all
      patients were administered 0.8 mg of intracoronary nitrates through the guiding
      catheter. Patients were then randomized. Seventeen patients (the NIT group) did
      not receive further treatment during the procedure, while the other 19 patients
      (the NIS group) received an additional 0.05 mg of intracoronary nisoldipine.
      Postprocedure treatment consisted of oral nitrates (80-120 mg/day) plus enalapril
      (10-20 mg/day) in the NIT group patients, and oral nisoldipine (20 mg/day) plus
      enalapril (10-20 mg/day) in the NIS group patients. The same treatment was
      maintained during the 6-month follow-up period. An echocardiographic study was
      performed at 1, 7, 30, 90, and 180 days following the procedure. Left
      ventriculography and coronary angiography were repeated at 1 and 180 days after
      the mechanical reperfusion. An exercise test was performed at 30, 90, and 180
      days following primary angioplasty. Left ventriculograms and two-dimensional
      echocardiograms were analyzed by a computerized system that evaluated left
      ventricular volumes, ejection fraction, segmental wall motion, and diastolic
      function (from the left ventricular volume curve). Under baseline conditions, the
      clinical and angiographic characteristics of the patients were similar in both
      treatment groups. The results showed a significantly earlier recovery of left
      ventricular systolic and diastolic function in the NIS group patients compared
      with those of the NIT group. Also, exercise capacity was significantly better at
      30 days in the NIS group. The findings of the present study provide further
      evidence that early reperfusion in acute myocardial infarction is likely to be
      followed by myocardial stunning. The vascular-selective organic calcium
      antagonist nisoldipine, administered at the onset of reperfusion, seems to
      attenuate postischemic stunning and to enhance the recovery of left ventricular
      function in this clinical subset.

PMID- 9140671
TI  - Clinical evidence that nisoldipine attenuates stunning in patients post
      infarction.

PMID- 9140672
TI  - Attenuation of stunning by the calcium antagonist nisoldipine in patients with
      myocardial infarction and early percutaneous transluminal coronary angioplasty.

PMID- 9140673
TI  - Effect of bunazosin and atenolol on glucose metabolism in obese, nondiabetic
      patients with primary hypertension.
AB  - Antihypertensive drugs, recommended by the World Health Organization for use in
      monotherapy, exert different effects on glucose and lipid metabolism. In our
      study we compared the effects of the beta-blocker atenolol (AT) and the alpha1
      blocker bunazosin (BU) on glucose metabolism. The doses administered were chosen
      to produce similar antihypertensive effects with both drugs. The study was
      conducted as a bicenter, parallel, controlled, and double-blind study. All
      patients suffered from mild to moderate primary hypertension, were obese (body
      mass index > 26 kg/m2), but were nondiabetic. After a drug-free period of 4
      weeks, patients were treated either with 6 and 12 mg of bunazosin (n = 15) or
      with 50 and 100 mg of atenolol (n = 17) once daily for 12 weeks. Glucose
      metabolism was measured by the iv glucose tolerance test (GTT) and the euglycemic
      hyperinsulinemic clamp test. The results show a similar blood pressure reduction
      with both drugs. However, their effects on glucose metabolism were significantly
      (p < 0.05) different: The area under the curve (AUC) of glucose in the iv GTT
      increased 26.8% during atenolol treatment but decreased 30% during bunazosin
      treatment. The same influence on the AUC of insulin was observed [AT +478.5 +/-
      441.8 (+22%) vs. BU, -588.5 +/- 411.1 (-22%)]. Similar changes were found in the
      glucose clamp test. The metabolic clearance rate increased 11.4% during bunazosin
      use and decreased 8.4% during atenolol use to the same degree that the insulin
      sensitivity index changed (BU +13.2% vs. AT -21.9%). The differences between the
      two treatment regimes were statistically significant (p < 0.05). These results in
      obese hypertensives confirm the well-known negative effects of beta-blockers on
      glucose metabolism. Additionally, they demonstrate that an alpha1-blocker such as
      bunazosin develops the same blood pressure-lowering effect as beta-blockers, but
      with a significantly better profile with regard to glucose metabolism. Therefore,
      the use of alpha1-blockers can be recommended for obese hypertensives without any
      special care for glucose metabolism.

PMID- 9140674
TI  - Both a calcium antagonist and ACE inhibitor reverse hypertrophy in hypertension
      but a calcium antagonist also depresses contractility.
AB  - The aim of this study was to compare the effects of a calcium antagonist,
      nicardipine SR, with an angiotensin-converting enzyme (ACE) inhibitor, alacepril,
      on the regression of left ventricular hypertrophy (LVH) and function. Twenty
      patients with LVH, aged 42-78 years, were treated with nicardipine SR or
      alacepril. Ten patients were treated with nicardipine SR (40-80 mg) for 21
      months, and the other 10 patients were treated with alacepril (25-100 mg) for 18
      months. All patients underwent echocardiography to assess left ventricular
      structure and function before and after the treatment. After nicardipine SR or
      alacepril treatment, blood pressure was decreased significantly from 176.0 +/-
      13.9/97.0 +/- 5.3 mmHg to 140.0 +/- 14.0/77.4 +/- 7.2 mmHg and from 168.2 +/-
      22.3/99.0 +/- 5.5 mmHg to 138.4 +/- 12.5/85.2 +/- 9.7 mmHg, respectively (both p
      < 0.01), whereas heart rate did not change (73.8 +/- 14.6 beats/min vs. 69.9 +/-
      13.5 beats/min and 71.6 +/- 9.7 vs. 65.8 +/- 8.1 beats/min, respectively). The
      left ventricular mass index decreased significantly from 133.2 +/- 11.7 g/m2 to
      114.4 +/- 15.7 g/m2 with nicardipine SR and from 137.1 +/- 14.8 g/m2 to 99.3 +/-
      23.0 g/m2 with alacepril (both p < 0.01). The fractional shortening, peak
      shortening rate, and peak lengthening rate all improved significantly after each
      treatment. The end-systolic wall stress/left ventricular end-systolic volume
      index, as an index of left ventricular contractility, was decreased significantly
      after treatment with nicardipine SR but was not changed after treatment with
      alacepril. In conclusion, both nicardipine SR and alacepril similarly reduced LVH
      and improved left ventricular systolic and diastolic function. However, alacepril
      did not alter left ventricular contractility, whereas nicardipine SR decreased
      left ventricular contractility.

PMID- 9140675
TI  - Natriuretic effect of nitrendipine is preceded by transient systemic and renal
      hemodynamic effects.
AB  - This study investigated whether the acute natriuretic effect of nitrendipine is
      related to its initial renal hemodynamic effects. We investigated 16 patients (10
      men and 6 women, mean age 52 +/- 2 years) with essential hypertension, whose
      treatment, if any, was stopped 3 weeks before the study. They were admitted to a
      metabolic ward for 9 days and kept on a constant sodium diet of 55 mmol/day.
      During two 24-hour experiments, subjects randomly received a single oral dose of
      placebo/nitrendipine 10 mg (group 1, n = 8) or placebo/nitrendipine 20 mg (group
      2, n = 8), according to a double-blind crossover study design. Patients fasted
      during the experiments, but their sodium intake was ensured by a constant
      intravenous saline infusion of 2.3 mmol/hr. Mean arterial pressure (MAP) and
      heart rate were determined for 5 hours following the administration of
      nitrendipine or placebo. Effective renal plasma flow (ERPF), glomerular
      filtration rate, active plasma renin concentration, angiotensin II, aldosterone,
      atrial natriuretic peptide, and catecholamines were determined every hour for 5
      hours. Hourly urine collections were used to assess sodium, potassium, and
      creatinine excretions. Relative to placebo, only in group 2 (nitrendipine 20 mg)
      was a fall in MAP and a rise in ERPF observed 2 hours after the start of the
      experiment. The effects, however, lasted only for 1 hour. No such changes were
      seen in group 1. In neither group did nitrendipine affect hormonal
      concentrations. Sodium excretion was enhanced after the 20-mg dose of
      nitrendipine only (p < 0.05). Nitrendipine 20 mg induced a significant increase
      in sodium excretion, which may be dissociated from its acute hemodynamic effects.

PMID- 9140676
TI  - Systemic and regional hemodynamic effects of gallopamil in patients with
      essential hypertension.
AB  - Systemic and regional hemodynamics were assessed in 10 patients with
      uncomplicated mild to moderate essential hypertension before and during
      gallopamil therapy. Cardiac output was measured in triplicate with indocyanine
      dye. Plasma volume and renal blood flow were measured radioisotopically.
      Immediately following the initial dose of a slow-release (SR) formulation of
      gallopamil, a significant fall in arterial pressure associated with a decreased
      total peripheral resistance and a reflex increase in heart rate and cardiac
      output were seen. Then, after 8-12 weeks of treatment, arterial pressure and
      total peripheral resistance remained reduced, but heart rate and cardiac output
      returned to pretreatment levels. Gallopamil also produced significant reductions
      in renal and splanchnic vascular resistance. Plasma volume and total blood volume
      did not change. Thus, gallopamil reduced arterial pressure and vascular
      resistances without fluid retention or prolonged reflexive changes.

PMID- 9140677
TI  - Ambulatory blood pressure monitoring in patients with essential hypertension
      treated with a new calcium antagonist, cilnidipine.
AB  - Cilnidipine (FRC-8653), a new dihydropyridine calcium antagonist, was given to 14
      hospitalized patients with essential hypertension, and 24-hour ambulatory blood
      pressure (BP) monitoring was performed. Once-daily administration of cilnidipine
      (5-20 mg) for 1-3 weeks decreased the 24-hour average BP significantly from 149
      +/- 4/88 +/- 2 mmHg to 141 +/- 3/82 +/- 2 mmHg without any change in the pulse
      rate. The decrease in ambulatory BP by cilnidipine was evident during the daytime
      (156 +/- 4/93 +/- 2 mmHg to 143 +/- 5/84 +/- 2 mmHg, p < 0.01 for systolic BP and
      p < 0.01 for diastolic BP), while it was mild during nighttime (141 +/- 4/80 +/-
      2 mmHg to 133 +/- 4/76 +/- 3 mmHg, p < 0.05 for systolic and ns for diastolic
      BP). The decrease in the ambulatory BP over the whole day and during the
      nighttime was significantly correlated with the basal ambulatory BP levels. When
      the subjects were divided into the high ambulatory BP (n = 7) and low ambulatory
      BP (n = 7) groups, the BP reduction by cilnidipine was evident throughout 24
      hours in the high ambulatory BP group, while it was mild and significant only
      during daytime in the low ambulatory BP group. In summary, once-daily cilnidipine
      exerts a sufficient and prolonged reduction of BP without an increase in the
      pulse rate in patients with hypertension. The potency of cilnidipine to decrease
      ambulatory BP may depend on the basal ambulatory BP level. Cilnidipine is thus a
      useful antihypertensive drug that may not cause an excessive decrease in BP or a
      reflex tachycardia.

PMID- 9140678
TI  - Prediction of the changes in cardiac output in association with preload reduction
      therapy in patients with hypertensive heart failure.
AB  - In treating patients with acute hypertensive heart failure we often try preload
      reduction therapy using diuretics or vasodilators, but this may frequently
      produce a considerable decrease in cardiac output, particularly in hypertensive
      patients with diastolic dysfunction. Therefore, it is important from the clinical
      standpoint to predict the change in cardiac output following preload-reduction
      therapy. The objective of this study was to assess whether the change in cardiac
      output in association with preload-reduction therapy is predictable before
      treatment by analysis of mitral flow velocity patterns in patients with
      hypertensive heart failure. Changes in left ventricular volumes and cardiac
      output in association with preload-reduction therapy and Doppler
      echocardiographic parameters of the mitral flow velocity pattern before treatment
      were studied in 18 patients with hypertensive heart failure. Cardiac output
      increased in six patients with systolic dysfunction (fractional shortening <
      25%). In the other 12 patients (those with normal systolic function), the changes
      in cardiac output were homogenous among the patients. In this subset there was a
      greater decrease in cardiac output in patients with a shorter deceleration time.
      Thus, analysis of deceleration time of the early diastolic filling wave before
      treatment may be useful in estimating the change in cardiac output following
      preload reduction in patients with hypertensive heart failure due to diastolic
      dysfunction.

PMID- 9140679
TI  - Contrasting actions of celiprolol and metoprolol on cardiac performance in normal
      volunteers.
AB  - A double-blind, randomized, placebo-controlled comparison of metoprolol (50 mg)
      and celiprolol (200 mg) was undertaken in nine normal volunteers. Rest and
      exercise (supine bicycle) hemodynamics were assessed at 0, 2, 4, 6, and 8 hours
      following single oral doses of medication administered at weekly intervals. The
      influence of the ancillary pharmacological properties of metoprolol and
      celiprolol on cardiac pumping indices was assessed from heart rate and peak
      aortic acceleration (pkA-Exerdop). Following placebo, the heart rate and pkA
      increased progressively with exercise duration and workload. Following metoprolol
      50 mg, the heart rate (-9.7 beat/min at 75 watts exercise) and pkA decreased. The
      blunting of acceleration was greater at higher exercise workloads (-6.7 m/sec2 at
      75 watts exercise). Celiprolol reduced heart rate (-6.9 beat/min at 75 watts
      exercise) without a change in pkA. The heart rate/pkA relationship showed
      significant parallel displacement, downwards after metoprolol but upwards after
      celiprolol. Thus, for a given heart rate increment there was a greater decrease
      in pkA after metoprolol compared with celiprolol. The different ancillary
      pharmacological profiles of metoprolol and celiprolol resulted in contrasting
      hemodynamic profiles. The observed differences in the heart rate/pkA
      relationships may be attributable to the peripheral actions of these agents. The
      therapeutic relevance of the better maintained cardiac pumping indices on
      celiprolol for ischemic patients with impaired cardiac function warrants further
      investigation.

PMID- 9140680
TI  - Lisinopril in the treatment of congestive heart failure in elderly patients:
      comparison versus captopril.
AB  - The present study was performed in order to compare the efficacy, safety, and
      tolerability of lisinopril, a long-acting angiotensin-converting enzyme (ACE)
      inhibitor, with captopril, the shorter acting ACE inhibitor available, in the
      treatment of elderly patients (mean age 70 +/- 0.5 years) with congestive heart
      failure (mean left ventricular ejection fraction 33.5 +/- 1%). The study was
      organized according to a double-blind, parallel-group, randomized multicenter
      protocol. After a 14-day placebo run-in period, patients were randomized to
      receive either lisinopril 5 mg orally once per day or captopril 12.5 mg orally
      once per day. The dose of the study drug could be doubled at 2-week intervals for
      6 weeks. The maximal dose was lisinopril 20 mg once per day or captopril 25 mg
      twice per day. The addition of either captopril or lisinopril to a regimen of
      diuretics caused a significant increase in exercise tolerance assessed by bicycle
      ergometry after 12 weeks of treatment (530 +/- 21 seconds vs. 431 +/- 13 seconds,
      p < 0.01; 555 +/- 19 seconds vs. 463 +/- 12 seconds, p < 0.01, respectively).
      Both drugs significantly increased left ventricular ejection fraction and stroke
      volume, were equally effective in improving NYHA class, and were well tolerated,
      with no differences detectable between treatments. The results of this study
      indicate that lisinopril 5-20 mg once daily is at least as effective and well
      tolerated as captopril 12.5-50 mg daily in the treatment of elderly patients with
      congestive heart failure.

PMID- 9140681
TI  - Coronary and cardiac sensitivity to the vasoselective benzothiazepine-like
      calcium antagonist, clentiazem, in experimental heart failure.
AB  - Recent evidence suggests that newer vasoselective dihydropyridine calcium
      antagonists are not cardiodepressant and may be useful in the treatment of heart
      failure. No data are available on the efficacy of clentiazem, a vasoselective
      benzothiazepine-like calcium antagonist, in this pathological condition.
      Therefore, our objective was to assess coronary and cardiac sensitivity to
      clentiazem in an experimental model of chronic heart failure (cardiomyopathic
      hamster, UM-X7.1, > 200 day old). Left ventricular developed pressure (LVP) and
      coronary flow changes were assessed in isolated, perfused failing hearts and in
      normal Syrian hamster hearts. Clentiazem dose-response curves for both coronary
      dilation and negative inotropic effects were determined under control conditions
      and in the presence of the nitric oxide (NO) synthase inhibitor, NG-nitro-L
      arginine (L-NAME, 30 microM), and the cyclooxygenase inhibitor, indomethacin (10
      microM). Baseline hemodynamics indicate a significant reduction in both LVP and
      coronary perfusion in failing hearts. Cardiac sensitivity to the negative
      inotropic effects of clentiazem were similar in normal and failing hearts (IC50 =
      677 nM and 734 nM, respectively). However, the clentiazem-induced increase in
      coronary flow was significantly attenuated in failing hearts (EC50 = 56 +/- 9 nM
      vs. 15 +/- 3 nM in normal hearts, p < 0.01). To better characterize the reduced
      coronary sensitivity to clentiazem in the presence of heart failure, the
      contributions of the NO synthase and the cyclooxygenase pathways were evaluated.
      Although coronary sensitivity to clentiazem was significantly reduced in the
      presence of L-NAME, this attenuation was of the same magnitude in normal and
      failing hearts, suggesting that coronary "desensitization" to clentiazem in
      failing hearts does not involve the NO synthase pathway. Experiments carried in
      the presence of indomethacin indicate that the reduced coronary sensitivity to
      clentiazem observed in failing hearts does not involve the cyclooxygenase
      pathway. In conclusion, reduced coronary sensitivity to the vasoselective calcium
      antagonist clentiazem was observed in the failing hamster heart, while no
      exacerbation of clentiazem's cardiodepressant actions was present. Although the
      mechanisms involved in the vascular desensitization to clentiazem are still
      unknown, our findings may provide an additional explanation for the variable
      efficacy of calcium antagonists in the treatment of heart failure.

PMID- 9140682
TI  - Sinus arrest and severe peripheral vasodilation following cardiopulmonary bypass
      in a patient taking nicorandil.

PMID- 9140683
TI  - Protection against global ischemia in the rabbit isolated heart 24 hours after
      transient adenosine A1 receptor activation.

PMID- 9140684
TI  - Blockade of ATP-dependent K+ channels in myocardium and coronary artery smooth
      muscle: a possible cause of increased cardiovascular mortality in sulfonylurea
      treated patients.

PMID- 9140685
TI  - Modified Valsalva maneuver for paroxysmal supraventricular tachycardia.

PMID- 9140686
TI  - Heparin and streptokinase.

PMID- 9140687
TI  - Heparin after acute myocardial infarction.
AB  - Heparin is commonly, but by no means universally, used after acute myocardial
      infarction. When used the dose, route of administration, and duration of therapy
      varies considerably. The role of heparin is reviewed with particular reference to
      its use in conjunction with other commonly used therapies, such as aspirin and
      thrombolytic agents. Intravenous heparin after thrombolytic therapy remains
      untested in patients treated with aspirin. When used, benefit is seen in a narrow
      aPTT range, and there have been unexpected increases in mortality in patients
      with the greatest heparin effect. The addition of delayed subcutaneous heparin to
      aspirin and thrombolytic therapy does not provide a mortality benefit. In
      patients not treated with thrombolysis, there is no clear evidence that heparin
      confers significant mortality benefit if patients are treated with aspirin.
      Heparin therapy may reduce the incidence of intraventricular thrombus after
      anterior wall infarction, but there is no clear evidence that it reduces the
      clinically important sequelae of cerebral embolism and stroke. Given concerns
      about increased hemorrhagic rates with heparin and unknown benefit, it is
      reasonable to conclude that its role in the management of patients with acute
      myocardial infarction remains unclear.

PMID- 9140688
TI  - Is heparin of value in the management of acute myocardial infarction?
AB  - The role of heparin in conjunction with thrombolytic therapy for the management
      of patients with acute myocardial infarction continues to be controversial. Many
      issues, including the possible benefits and risks of this therapy, are
      unresolved. Administration of high-dose subcutaneous heparin in the presence of
      thrombolytic therapy results in a significant mortality reduction during the
      treatment period of 55 lives saved per 10,000 patients treated (p < 0.01). At 35
      days mortality is not significantly decreased by 22 lives and 18 nonfatal
      infarctions, at a cost of 32 transfusions and 6 strokes (half of which result in
      full recovery) per 10,000 patients treated. There have been fewer than 1250
      patients randomized in trials comparing intravenous heparin with no heparin in
      patients receiving thrombolytic therapy and aspirin. These trials are too small
      to draw reliable conclusions, although several trials have suggested that
      intravenous heparin is beneficial for maintaining patency after t-PA therapy. In
      the the Global Use of Streptokinase and t-PA for Occluded Coronary Arteries
      (GUSTO) trial, patients receiving streptokinase were randomized to receive either
      delayed subcutaneous heparin or intravenous heparin. There were no differences in
      clinical endpoints. However, despite 36% crossover to intravenous heparin among
      patients randomized to receive subcutaneous heparin with streptokinase, patency
      of the infarct-related artery was 17% higher (84% vs. 72%, p < 0.05) at 5-7 days
      in patients randomized to receive intravenous heparin and streptokinase. This
      significant difference could potentially translate into an important effect on
      long-term prognosis. Therapy for acute myocardial infarction should include
      aspirin and a thrombolytic agent for patients without contraindications. Based on
      the current evidence, it is reasonable to also administer intravenous heparin
      with either streptokinase or TPA.

PMID- 9140689
TI  - Ginkgo biloba extract (EGb 761) pretreatment limits free radical-induced
      oxidative stress in patients undergoing coronary bypass surgery.
AB  - A growing body of evidence supports the trigger role of free radicals in the
      delayed functional and metabolic myocardial recovery following cardiopulmonary
      bypass (CPB) in humans, thus opening the field to specific therapies. This
      clinical study was designed to evaluate, in 15 patients undergoing aortic valve
      replacement, whether the extent of CPB- and reperfusion-induced lipid
      peroxidation, ascorbate depletion, tissue necrosis, and cardiac dysfunction is
      reduced by orally administered EGb 761, a Ginkgo biloba extract with potent in
      vitro antiradical properties. Patients received either EGb 761 (Tanakan, 320
      mg/day, n = 8) or a matching placebo (n = 7) for 5 days before surgical
      intervention. Plasma samples were obtained from the peripheral circulation and
      the coronary sinus at crucial stages of the operation (i.e., before incision,
      during ischemia, and within the first 30 minutes post-unclamping), and up to 8
      days postoperatively. Upon aortic unclamping, EGb 761 inhibited the transcardiac
      release of thiobarbituric acid-reactive species (p < 0.05), as assessed by high
      performance liquid chromatography, and attenuated the early (5-10 minute)
      decrease in dimethylsulfoxide/ascorbyl free radical levels, an electron spin
      resonance index of the plasma ascorbate pool (p < 0.05). EGb 761 also
      significantly reduced the more delayed leakage of myoglobin (p = 0.007) and had
      an almost significant effect on ventricular myosin leakage (p = 0.053, 6 days
      postoperatively). The clinical outcome of recovery of treated patients was
      improved, but not significantly, compared with untreated patients. Our results
      demonstrate the usefulness of adjuvant EGb 761 therapy in limiting oxidative
      stress in cardiovascular surgery and suggest the possible role of highly
      bioavailable terpene constituents of the drug.

PMID- 9140690
TI  - Acute effects of celiprolol on angiographically normal and stenotic coronary
      arteries.
AB  - Unselective and beta 1-selective beta-blockers may induce vasoconstriction of
      normal and stenotic epicardial coronary arteries. To analyze the influence of the
      "vasodilatory" beta-blocker celiprolol on coronary vasomotility, 0.4 mg
      celiprolol/kg were intravenously infused over 4 minutes in 13 patients with
      coronary artery disease. Coronary angiograms were taken before (control) and at
      4, 6, 8, 10, 15, and 20 minutes after the onset of infusion and 4 minutes after
      final sublingual administration of 0.4 mg nitroglycerin. Quantitative analysis of
      cinefilms demonstrated no significant diameter changes in angiographically normal
      coronary segments and stenoses. The vasodilatory capacity of normal segments (18
      +/- 12%; p < 0.001) and stenoses (17 +/- 14%; p < 0.01) was proven by
      nitroglycerin. Systolic blood pressure, heart rate, and pulmonary wedge pressure
      revealed no significant changes with celiprolol. Thus, celiprolol exerts no
      vasoconstricting effects on angiographically normal and stenotic coronary
      arteries.

PMID- 9140692
TI  - Emerging class III antiarrhythmic agents: mechanism of action and proarrhythmic
      potential.
AB  - The goal of developing an antiarrhythmic agent effective against malignant
      ventricular arrhythmias while maintaining a low side-effect profile remains
      elusive. The class III drugs amiodarone and sotalol are the best available
      agents. However, both drugs possess properties outside the realm of a pure class
      III effect, and their use is limited by a variety of dose-related side effects.
      There are several drugs with more selective class III properties currently in
      development. This review provides an overview of the optimal characteristics of
      an effective theoretical class III drug and a summary of the properties of a
      number of class III drugs under active investigation. An ideal class III
      antiarrhythmic agent for a reentrant arrhythmia should provide use-dependent
      prolongation of the action potential duration with slow onset and rapid offset
      kinetics. This drug would prolong the effective refractory period of cardiac
      tissue selectively at the rapid heart rates achieved during ventricular
      tachycardia or fibrillation with a delayed onset of action, and a rapid
      resolution of its effects on resumption of physiologic heart rates. With little
      effect on the refractory period at normal or slow heart rates, the ability to
      induce torsade de pointes would be lessened. In contrast to these ideal
      properties, most currently available and investigational agents have a reverse
      use-dependent effect on the action potential duration, producing more effects on
      the refractory period at slower heart rates. This property results in part from
      preferential block of the rapidly activating component of the delayed rectifier
      potassium channel (IKr), with little or no effect on the slowly activating
      component (IKs). The development of a drug with favorable blocking kinetics that
      selectively blocks IKs may results in lower proarrhythmic events while still
      maintaining effective antiarrhythmic properties.

PMID- 9140691
TI  - Acute hemodynamic effects of amlodipine 15 days after a myocardial infarction in
      normotensive patients treated with atenolol.
AB  - The acute hemodynamic effects of 20 mg iv amlodipine were evaluated in a placebo
      controlled study in 16 normotensive patients 15 +/- 1 days after an acute
      myocardial infarction by covariance analysis. Atenolol was given orally for at
      least 1 week before the study to maintain the heart rate between 50 and 60
      beats/min. All patients were given two doses of 10 mg of amlodipine, or 10 ml of
      a placebo twice, in i.v. infusion lasting 2 minutes each. Hemodynamic data were
      collected during the control period and 15 minutes after each of the two
      amlodipine or placebo infusions. At the time of the last measurements, 15 minutes
      after the second amlodipine or placebo infusion, the plasma amlodipine level was
      31 +/- 16 micrograms/l and the plasma atenolol level was 773 +/- 564 mu/l in the
      amlodipine group versus 795 +/- 916 micrograms/l in the placebo group. There were
      no chronotropic, dromotropic, or inotropic effects. The main hemodynamic effect
      was a fall in systemic vascular resistance (1548 +/- 591 dynes.sec.cm-5 to 1176
      +/- 526 dynes.sec.cm-5, p = 0.045) with decreases in aortic pressure and in the
      left ventricular stroke work index. The left ventricular ejection fraction was 51
      +/- 12% in the placebo group and 56 +/- 15% in the amlodipine group (ns) during
      the control period, and did not change after infusion of placebo or amlodipine.
      Left ventricular compliance seemed to be enhanced by amlodipine, because the end
      diastolic left ventricular volume index rose from 82 +/- 11 ml/m2 to 87 +/- 11
      ml/m2 (p = 0.026) 15 minutes after the beginning of the second infusion of 10 mg
      of amlodipine, without any change in end-diastolic left ventricular pressure.
      Intravenous infusion of 20 mg of amlodipine is well tolerated 15 days after acute
      myocardial infarction in normotensive patients without deeply depressed left
      ventricular systolic function and chronically treated with atenolol. The main
      hemodynamic effects observed are potentially useful for such patients.

PMID- 9140693
TI  - Activity of Procanbid, procainamide twice-daily formulation, to suppress
      ventricular premature depolarizations. The Study Group Investigators.
AB  - Procainamide is a class IA antiarrhythmic drug indicated for the treatment of
      life-threatening or symptomatic ventricular arrhythmias. The current sustained
      release formulation requires 6-hour dosing (qid). To improve patient compliance,
      a new sustained-release formulation for twice-daily (bid) administration has been
      developed (Procanbid, Parke-Davis). This study assesses the pharmacologic
      equivalence of the bid and qid formulations in the suppression of symptomatic
      ventricular premature depolarizations (VPDs). Fourteen centers enrolled a total
      of 99 patients with frequent symptomatic VPDs (average > or = 20 VPDs/hr) who
      previously responded to and tolerated the procainamide qid formulation. During
      the first week of the double-blind phase, patients were randomized to either
      placebo or procainamide dosages of 1000, 2000, or 4000 mg/d (bid or qid
      formulations). In the second week, the patients were crossed over to the
      alternate formulation. Seventy-seven patients qualified for the primary activity
      analysis. The bid and qid formulations showed comparable effectiveness in the
      suppression of mean VPDs with a linear dose-response relationship. The VPD
      suppression was not attenuated towards the end of the dosing interval for either
      formulation. Sixty-eight of these patients entered an optional 1-year extension
      to receive the bid formulation. Thirty-seven (54%) patients had adverse effects.
      Of those, 15 (22%) had side effects considered treatment related. Most of the
      adverse events occurred during the first 6 weeks of treatment. Only a few
      patients (8%) withdrew as a consequence of treatment with the bid formulation.
      The overall safety profile of the bid formulation was similar to other
      formulations, and the procainamide bid formulation has a low proarrhythmic rate
      (< 3%). In conclusion, the effectiveness of the twice-daily formulation of
      procainamide in the suppression of VPDs is comparable to the currently available
      qid formulation.

PMID- 9140694
TI  - Regression of chronic hypoxia-induced pulmonary hypertension, right ventricular
      hypertrophy, and fibrosis: effect of enalapril.
AB  - Chronic hypoxia induces pulmonary hypertension and right ventricular hypertrophy.
      These changes are completely reversible, except for persistent myocardial
      fibrosis. The aim of the present study was to determine whether treatment with
      the angiotensin-converting enzyme (ACE) inhibitor enalapril can reduce the
      ventricular collagen content in animals recovering from chronic hypoxia. Adult
      male Wistar rats were exposed to intermittent high-altitude hypoxia simulated in
      a barochamber (7000 m, 8 hr/day, 5 days a week, 24 exposures), then transferred
      to normoxia and divided into two groups: (a) treated with enalapril (0.1 g/kg/day
      for 60 days) and (b) without treatment. The corresponding control groups were
      kept under normoxic conditions. Enalapril significantly decreased the heart rate,
      systemic arterial pressure, and absolute left and right ventricular weights in
      both hypoxic and control rats; on the other hand, the pulmonary blood pressure
      was unchanged. The content and concentration of collagen was reduced in both
      ventricles of enalapril-treated hypoxic and control animals by 10-26% compared
      with the corresponding untreated groups. These data suggest that the partial
      regression of cardiac fibrosis due to enalapril may be independent of the
      pressure load.

PMID- 9140695
TI  - At least three neurotransmitter systems mediate a stress-induced increase in c
      fos mRNA in different rat brain areas.
AB  - 1. Protooncogene c-fos mRNA levels were determined in the rat cerebral cortex,
      hippocampus, and cerebellum after exposure to a combined forced swimming and
      confinement stress. The stress resulted in an increase in c-fos mRNA levels in
      all three brain areas. 2. In an effort to elucidate the neurotransmitter systems
      involved in this stress-induced increase, animals were injected, prior to
      exposure to the stress, with either diazepam, MK-801, or propranolol. 3. In both
      the cerebral cortex and the hippocampus the stress-induced increase in c-fos mRNA
      was inhibited by MK-801, suggesting that it is mediated via NMDA receptors. In
      the hippocampus, propranolol had a similar effect, indicating that beta
      adrenergic receptors are also involved in the stress-induced increase in c-fos
      mRNA. 4. On the other hand, the increase in c-fos mRNA produced by the stress of
      the injection was inhibited in the cerebral cortex by diazepam or propranolol and
      in the hippocampus only by diazepam. Furthermore, administration of MK-801
      resulted in an increase in c-fos mRNA in the hippocampus of the nonstressed
      animals. In the cerebellum no one of the three drugs employed affected c-fos mRNA
      levels in either stressed or nonstressed animals. 5. Our results thus show that
      various forms of stress activate, in different brain areas, neurons with either
      NMDA, beta-adrenergic, and/or GABA-A receptors.

PMID- 9140697
TI  - Single versus repetitive spiking to the current stimulus of A-beta
      mechanosensitive neurons in the crotaline snake trigeminal ganglion.
AB  - 1. Intrasomal recordings of potentials produced by current stimulation in vivo
      were made from 24 (A-beta) touch and 19 vibrotactile neurons in the trigeminal
      ganglion of 29 crotaline snakes, Trimeresurus flavoviridis. 2. Usually touch
      neurons responded with a single action potential at the beginning of a prolonged
      depolarizing pulse, whereas all vibrotactile neurons responded with multiple
      spikes. 3. The electrophysiological parameters examined were membrane potential,
      threshold current, input resistance and capacitance, time constant, rebound
      latency, and its threshold current. Touch neurons had higher input resistance
      (and lower input capacitance) than vibrotactile neurons. 4. In conclusion,
      current injection, which elicits a single or multiple spiking, seems a useful way
      to separate touch neurons from vibrotactile neurons without confirming the
      receptor response, and some membrane properties are also specific to the sensory
      modality.

PMID- 9140696
TI  - Time course and involvement of protein kinase C-mediated phosphorylation of
      F1/GAP-43 in area CA3 after mossy fiber stimulation.
AB  - 1. Protein kinase C (PKC) activity and phosphorylation of F1/growth associated
      protein (GAP)-43, a PKC substrate, have been proposed to play key roles in the
      maintenance of long-term potentiation (LTP) at the synapses of Schaffer
      collateral/commissural on pyramidal neurons in CA1 (Akers et al., 1986). We have
      studied in the involvement of PKC and PKC-dependent protein phosphorylation of
      F1/GAP-3 in in vitro LTP observed at the synapses of mossy fiber (MF) on CA3
      pyramidal neurons of rat hippocampus by post hoc in vitro phosphorylation. 2.
      After LTP was induced in CA3 in either the presence or absence of D-2-amino-5
      phosphonovaleric acid (AP5), an NMDA receptor antagonist, the CA3 region was
      dissected for in vitro phosphorylation assay. In vivo phosphorylation of F1/GAP
      43 was increased in membranes at 1 and 5 min after tetanic stimulation (TS) but
      not at 60 min after TS. 3. The degree of phosphorylation of F1/GAP-43 in the
      cytosol was inversely related to that in membranes at each time point after LTP.
      4. The similar biochemical changes obtained from either control slices or AP5
      treated slices indicate that LTP and the underlying biochemical changes are
      independent of the NMDA receptor. Immunoreactivity of the phosphorylated F1/GAP
      43 in LTP slices was not significantly different from control, indicating that
      results from western blotting and post hoc in vitro phosphorylation are
      consistent. 5. Post hoc in vitro phosphorylation of F1/GAP-43 was PKC-mediated
      since phosphorylation of F1/GAP-43 was altered by the PKC activation cofactors,
      Ca2+, phosphatidylserine and phorbol ester. 6. Calmodulin (CaM) at > 5 microM
      inhibited phosphorylation, consistent with the presence of CaM-binding activity
      at the site on F1/GAP-43 acted upon by PKC. 7. We conclude that phosphorylation
      of F1/GAP-43 is associated with the induction but not the maintenance phase of MF
      CA3 LTP.

PMID- 9140699
TI  - Involvement of CYP3A4 and CYP2D6 in the metabolism of haloperidol.
AB  - 1. Human cytochrome P450 (CYP) isoenzymes expressed in a human cell line were
      used to elucidate their involvement in the metabolism of haloperidol (HAL). 2. It
      was found that CYP3A4 catalyzes the metabolism of HAL to HAL 1,2,3,6
      tetrahydropyridine (HTP). HTP is further metabolized to HAL pyridinium (HP+) by
      both CYP3A4 and CYP2D6. 3. CYP3A4 and CYP2D6 are also responsible for the N
      dealkylation of HAL. The N-dealkylation of reduced HAL (RH) was observed, which
      is catalyzed by CYP3A4. In addition, CYP3A4 also catalyzes the oxidation of RH
      back to HAL. 4. These results are discussed in terms of the metabolic
      interactions of HAL with other drugs and how this knowledge may be used to reduce
      the movement disorders induced by HAL.

PMID- 9140698
TI  - Common molecular mechanisms in field- and agrin-induced acetylcholine receptor
      clustering.
AB  - 1. The aggregation of acetylcholine receptors at the developing neuromuscular
      junction is critical to the development and function of this synapse. In vitro
      studies have shown that receptor aggregation can be induced by the finding of
      agrin to the muscle cell surface and by the electric field-induced concentration
      of a (nonreceptor) molecule at the cathodal cell pole. 2. We report here on the
      interaction between agrin binding and electric fields with respect to the
      distribution of receptors and agrin binding sites. 3. (a) Pretreatment of cells
      with agrin completely blocks the development of field-induced receptor clusters.
      (b) Field-induced aggregation of receptors precedes the field-induced aggregation
      of agrin binding sites by approximately 30 min. (c) Electric fields prevent agrin
      induced receptor clustering despite the presence of agrin binding sites and
      freely diffusing receptors. 4. These results indicate that another membrane
      component-but not the agrin binding site and not the receptor-is required for
      agrin-induced receptor clustering. They also suggest that electric fields and
      agrin cause receptor clustering via common molecular mechanisms.

PMID- 9140700
TI  - Sequence and functional analysis of the 5'-flanking region of the mouse growth
      inhibitory factor gene.
AB  - 1. The growth inhibitory factor (GIF) is a 68-amino acid protein which is capable
      of inhibiting the growth of neuronal cells in vitro. 2. We have cloned and
      sequenced the 5'-flanking region of the mouse GIF gene, which spans from the
      transcriptional initiation site to the -1854 nucleotide. 3. This region contains
      sequences homologous to hgcs, SPE, and the JCV silencer domain that functions in
      a glial cell specific manner. This region also contains two metal responding
      elements and putative binding sites for AP-1, AP-2, Sp-1, SP-2, NF-1, and CREB.
      4. An analysis of the reporter plasmids containing the various regions of the 5'
      flanking sequence revealed that the region indeed functioned in a tissue-specific
      manner in glial cells and that the region between -328 and 175 is responsible for
      suppression, while the region between -175 and -49 is involved in the activation
      of gene expression.

PMID- 9140701
TI  - Different behavior of lactotroph cell subpopulations in response to angiotensin
      II and thyrotrophin-releasing hormone.
AB  - 1. In the present investigation we have extended the study of lactotroph
      subpopulations in primary pituitary cell cultures. Male rats with or without
      previous estrogenization followed by A-II or TRH treatments were selected as
      experimental models. 2. The TRH increased up to 50% the PRL released in both
      whole and OROX+EB rats (P < 0.05). In contrast, A-II treatment introduced no
      changes in PRL secretion from cell cultures derived from whole male rats but
      attained a significant augmentation (about 75%) of PRL secreted by ORQX+EB
      pituitary cells. 3. The addition of TRH and A-II to cultures of ORQX+EB-derived
      lactotrophs induced cytological changes compatible with a high secretory
      activity. In estrogen-treated rats the prevailing lactotroph subpopulation is
      type I. In cell cultures from control and A-II treated whole male pituitaries,
      the majority of lactotrophs consists of atypical subpopulations of II and III
      cells, with smaller secretory granules (between 150 and 300 nm in diameter). 4.
      Morphometry of immunostained lactotrophs performed on light microscopic
      preparations revealed that about 30-36% of the total cell count were lactotrophs.
      This percentage was fixed and did not change significantly after TRH and A-II
      treatments. 5. The present results confirm the presence of morphological and
      functional subtypes of lactotroph cells in rat pituitary. Typical PRL cell
      population shows the highest responsiveness to angiotensin II and TRH action.
      This functional heterogeneity of lactotroph subtypes may reflect an important and
      scarcely explored factor in the regulatory process of prolactin secretion.

PMID- 9140703
TI  - Uremia enhances the blood pressure response to erythropoietin.
AB  - To investigate the role of uremia in the development of human recombinant
      erythropoietin (r-HuEPO)-induced hypertension, Wistar rats were divided into a
      uremic (subtotal nephrectomy) and a control group. After three weeks, both groups
      were again divided and each subgroup received either r-HuEPO (100 u/kg s.c., 3
      times weekly) or the vehicle for a further 3 weeks. Hematocrit, blood pressure
      and blood chemistry were measured prior to surgery, before either vehicle or r
      HuEPO treatment and before euthanasia. The uremic group developed anemia,
      hypertension and all the biochemical features observed in humans with end-stage
      renal disease. r-HuEPO therapy increased hematocrit from 29 +/- 2.5% to 46 +/- 2%
      (p < 0.01) in the uremic rats. The mean baseline blood pressure was 119 +/- 10
      mmHg. At week 3, mean blood pressure was unchanged in control rats, but it was
      increased to 151 +/- 5 mmHg (p < 0.01) in the nephrectomized group. At week 6,
      mean blood pressure in the untreated uremic rats remained unchanged from week 3,
      but blood pressure in the uremic animals treated with r-HuEPO increased
      significantly to 187 +/- 8 mmHg (p < 0.01). There was no significant correlation
      between hematocrit and blood pressure in the r-HuEPO treated uremic group (r =
      0.01, NS). r-HuEPO had no effect on blood pressure in control rats despite a
      significant increase in hematocrit. These results indicate that the blood
      pressure response to r-HuEPO is enhanced in rats with chronic renal failure.

PMID- 9140702
TI  - Biochemical and physiological evidence that carnosine is an endogenous
      neuroprotector against free radicals.
AB  - 1. Carnosine, anserine, and homocarnosine are endogenous dipeptides concentrated
      in brain and muscle whose biological functions remain in doubt. 2. We have tested
      the hypothesis that these compounds function as endogenous protective substances
      against molecular and cellular damage from free radicals, using two isolated
      enzyme systems and two models of ischemic brain injury. Carnosine and
      homocarnosine are both effective in activating brain Na, K-ATPase measured under
      optimal conditions and in reducing the loss of its activity caused by incubation
      with hydrogen peroxide. 3. In contrast, all three endogenous dipeptides cause a
      reduction in the activity of brain tyrosine hydroxylase, an enzyme activated by
      free radicals. In hippocampal brain slices subjected to ischemia, carnosine
      increased the time to loss of excitability. 4. In in vivo experiments on rats
      under experimental hypobaric hypoxia, carnosine increased the time to loss of
      ability to stand and breath and decreased the time to recovery. 5. These actions
      are explicable by effects of carnosine and related compounds which neutralize
      free radicals, particularly hydroxyl radicals. In all experiments the effective
      concentration of carnosine was comparable to or lower than those found in brain.
      These observations provide further support for the conclusion that protection
      against free radical damage is a major role of carnosine, anserine, and
      homocarnosine.

PMID- 9140704
TI  - Newborn organ weight and spontaneous hypertension: recombinant inbred strain
      study.
AB  - Heart and kidney weight of newborn rats was studied in two progenitor strains
      (Brown Norway-BN, and spontaneously hypertensive rats-SHR) and in 31 recombinant
      inbred (RI) strains developed by inbreeding of F2 cross derived from these two
      progenitors. The relative weight of both organs was significantly higher in SHR
      newborns than in BN ones. No differences in relative DNA, protein and water
      contents were detected in hearts from SHR and BN newborns. On the other hand, in
      SHR kidneys there was lower DNA and protein content accompanied by a higher water
      content. This suggested that kidneys of SHR babies had less cells with higher
      water content. The average body weight of newborns in individual RI strains was
      continuously distributed between both progenitor strains but more RI strains
      resembled values of SHR newborns. The opposite was true for relative heart and
      kidney weights where the predominant influence of BN genes was visible. Moreover,
      there was an important difference between two reciprocal crosses of RI strains
      because the relative heart weight was clustered around SHR values only in BxH but
      not in HxB cross. This was, however, not observed for body weight and relative
      kidney weight. No significant correlation between blood pressure of adult males
      and body weight or relative organ weights of newborns of RI strains was found. On
      the other hand, relative heart and kidney weights of newborns correlated
      positively with the same parameters in adult males of respective RI strains.
      Additionally, relative heart weight of newborns was related positively to blood
      pressure of their mothers only in HxB cross that was derived from SHR females. It
      can be concluded that 1) kidney enlargement observed in newborn SHR is due to
      increased water content, 2) organ weight in adulthood can be predicted from
      newborn organ weight, and 3) heart weight in newborns correlated significantly
      with maternal blood pressure in HxB but not in BxH cross. It should be noted that
      the relationship between heart and/or kidney weight at birth and blood pressure
      in adulthood has not been proven to be significant (at p < 0.05 level) in Prague
      set of recombinant inbred strains.

PMID- 9140706
TI  - Intracellular free Ca2+ and basal Mn2+ influx in cultured aortic smooth muscle
      cells from spontaneously hypertensive and normotensive Wistar-Kyoto rats.
AB  - Numerous studies investigating the possible role of altered Ca2+ homeostasis in
      hypertension have compared resting and agonist-stimulated intracellular free Ca2+
      ([Ca2+]i) in cultured aortic smooth muscle cells from spontaneously hypertensive
      (SHR) and normotensive Wistar-Kyoto (WKY) rats. However, such studies have not
      given consistent results. Differences in the method used to load cells with the
      Ca(2+)-sensitive indicator fura-2 have been investigated here as a possible
      source of variability between studies. We also describe the adaptation of a
      fluorescence technique for the assessment of basal Ca2+ permeability in SHR and
      WKY through the measurement of Mn2+ influx. The results are consistent with the
      hypothesis that basal Ca2+ influx is elevated in cultured aortic smooth muscle
      cells from SHR compared to those from WKY. However, this was not reflected as a
      significant difference between the two strains in basal or angiotensin II (200
      nmol/L)-stimulated [Ca2+]i. Furthermore, this result was not dependent on the
      protocol used to load cells with fura-2. Hence, measurement of bulk [Ca2+]i does
      not appear to be the most sensitive parameter for altered Ca2+ homeostasis in
      SHR. Other compartments of the cell may better reflect altered Ca2+ fluxes in
      hypertension and are discussed in this work.

PMID- 9140705
TI  - The role of the hypothalamic-pituitary-adrenal (HPA) axis in the regulation of
      blood pressure.
AB  - The role of the HPA axis in blood pressure regulation was examined in 6 normal
      male volunteers by comparing haemodynamic and hormonal effects of placebo,
      captopril, and dexamethasone given in random order for two days. The average 24
      hour systolic and mean arterial pressures on placebo (135 +/- 6 and 93 +/- 2 mmHg
      respectively) were significantly higher than on captopril (118 +/- 1 and 85 +/- 1
      mmHg respectively, p < 0.05) but there were no significant changes on
      dexamethasone compared with placebo (128 +/- 3 and 89 +/- 3 mmHg respectively).
      There were no differences in the average 24-hour diastolic blood pressures or
      heart rates, nor the day-night differences, night:day ratios or percentage
      changes in blood pressure and heart rate between treatments. Captopril
      significantly increased active plasma renin concentration, whilst dexamethasone
      decreased cortisol concentration. These results confirm the role of the renin
      angiotensin system in the regulation of blood pressure in normal subjects but
      suggest that the HPA axis does not play a major role in determining ambulatory
      blood pressure or day-night variability in the short term.

PMID- 9140707
TI  - Cardiovascular effects of oxymetazoline and UK14,304 in conscious and pithed
      rats.
AB  - Relatively selective alpha 2-adrenoceptor agonists have proven useful in a
      variety of therapeutic situations including hypertension, glaucoma and withdrawal
      from opiate addiction. In particular, oxymetazoline (OXY) and UK14,304 (UK) have
      been used in subclassifying alpha 2-adrenoceptors and imidazoline receptors. We
      evaluated the cardiovascular effects of OXY and UK in conscious and pithed rats
      in the presence and absence of efaroxan (EFA), idazoxan (IDA) and rauwolscine
      (RAU). Both OXY or UK (1, 5 and 10 micrograms/kg, i.v.) increased blood pressure
      (BP) and reduced heart rate (HR) in conscious rats. In pithed rats, OXY and UK
      each increased BP to a greater extent than that observed in conscious rats, but
      HR was not affected. BP increases following sympathetic nerve stimulation in the
      pithed rats were not affected by OXY but were reduced by UK at 0.1 Hz and 0.3 Hz.
      HR responses to nerve stimulation in pithed rats were reduced after OXY at all
      frequencies, but only at 0.1 Hz following UK. EFA, IDA and RAU inhibited the
      pressor responses of UK, with EFA being most potent. OXY-induced pressor
      responses were inhibited by all three antagonists, RAU being the least potent. HR
      responses to either OXY or UK were not affected by the antagonists. Taken
      together, the data suggest that: 1) alpha 2-adrenoceptors contribute less to the
      vascular response to OXY than to UK based upon the antagonistic effect of RAU; 2)
      prejunctional I1 receptors maybe more prevalent in the heart than in vascular
      tissue based upon the response to OXY in pithed rats. Thus, the heterogeneity
      among receptors mediating cardiac and vascular responses are complex.

PMID- 9140708
TI  - Acceleration of hypertensive cerebral injury by the inhibition of xanthine
      xanthine oxidase system in stroke-prone spontaneously hypertensive rats.
AB  - It is well-known that, in ischemic cerebral injury, a free radical and its
      byproducts are generated by xanthine-xanthine oxidase system and eliminated by
      scavengers such as superoxide dismutase (SOD), catalase, uric acid and ascorbic
      acid. To investigate the possible involvement of the xanthine-xanthine oxidase
      system in hypertensive cerebral injury, we examined chronological changes in uric
      acid level in the cerebral cortex and the effects of the inhibition of xanthine
      oxidase or catalase using stroke-prone spontaneously hypertensive rats (SHRSP).
      In young SHRSP, uric acid content was lower than age-matched Wistar-Kyoto rats
      (WKY), but in mature SHRSP strongly exposed to oxidative stress uric acid content
      had risen dramatically. Administration of allopurinol, an inhibitor of xanthine
      oxidase, caused a marked decrease in uric acid content. In these SHRSP, cerebral
      injury was much more intense compared to the control group. On the other hand,
      administration of aminotriazole, an inhibitor of catalase, did not affect the
      brain pathology of SHRSP, in spite of a mild reduction in tissue uric acid
      content. These results suggest that the xanthine-xanthine oxidase system is not
      the major source of free radical generation in hypertensive cerebral injury.
      Moreover, the results also suggest that tissue uric acid may have a key role for
      the incidence of hypertensive cerebral injury in SHRSP.

PMID- 9140709
TI  - Reflex sympathetic function in cortisol-induced hypertension in humans.
AB  - Nine healthy male subjects underwent measurement of reflex sympathetic function,
      pressor responsiveness and baroreflex sensitivity to phenylephrine (PE) and
      glyceryltrinitrate (GTN) before (C1) and following six days of treatment (E6)
      with cortisol (F), 200 mg/day. Seven subjects had washout studies (W) performed
      at least two weeks following the end of treatment. The BP responses to head tilt,
      isometric exercise and mental arithmetic were unaltered by F, however, there was
      a significant diminution of the diastolic BP response to cold pressor stimulus
      (delta DBP: 19 +/- 3 vs 25 +/- 5 vs 27 +/- 5 mmHg; E6 vs C1 vs W, p < 0.05 C1 vs
      E6 and W). Baroreflex sensitivity to PE was increased (28 +/- 3 vs 19 +/- 2
      ms/mmHg, E6 vs C1, p = 0.03). These data demonstrate that increased BP during F
      treatment is not attributable to increased SNS activity, and suggest that SNS
      activity may be decreased by F.

PMID- 9140710
TI  - Effects of quinapril hydrochloride in patients with essential hypertension and
      impaired renal function.
AB  - The short-term effects of administration of an angiotensin-converting enzyme
      (ACE) inhibitor, quinapril hydrochloride (quinapril) (5-10 mg/day), for 12 weeks
      on blood pressure and renal function were evaluated in 8 patients (60.5 +/- 7.3
      years old, mean +/- SD) with mild to moderate essential hypertension and mild
      impairment of renal function due to nephrosclerosis. Systolic blood pressure and
      diastolic blood pressure were significantly reduced from 163.0 +/- 4.0 to 132.3
      +/- 17.6 mmHg (p < 0.01) and from 98.3 +/- 4.6 to 81.5 +/- 6.4 mmHg (p < 0.001),
      respectively, before to after treatment. Both renal plasma flow (RPF) and
      glomerular filtration rate (GFR) were significantly increased in all patients,
      from 203.9 +/- 33.3 to 245.4 +/- 36.7 ml/min/1.73 m2 (p < 0.01), and from 43.4 +/
      6.4 to 53.5 +/- 4.6 ml/min/1.73 m2 (p < 0.05), respectively. Short-term
      quinapril administration was beneficial to renal function in patients with
      essential hypertension and impaired renal function.

PMID- 9140711
TI  - Different secretion patterns of adrenomedullin, brain natriuretic peptide, and
      atrial natriuretic peptide during exercise in hypertensive and normotensive
      subjects.
AB  - The purpose of this study was to investigate the effect of exercise on plasma
      concentrations of adrenomedullin, brain natriuretic peptide (BNP), and atrial
      natriuretic peptide (ANP) in patients with essential hypertension (n = 15) and in
      normotensive controls (n = 10). Exercise consisted of two fixed workloads, 40 and
      80 watts of work load using a supine bicycle ergometer. Plasma levels of all
      three peptides at rest were significantly higher in hypertensives than in
      controls. Plasma concentrations of ANP increased with exercise in both groups and
      had greater increments in hypertensive patients than in normotensives. Plasma
      concentrations of BNP increased only in patients with hypertension and the levels
      of increase correlated with basal plasma BNP levels (r = 0.94, p < 0.001) and
      with left ventricular mass (r = 0.62, p < 0.01) determined by echocardiography.
      In contrast, plasma adrenomedullin did not change with exercise in either group.
      These results suggest that secretion patterns of these peptides are regulated by
      different mechanisms and that the amount and kind of peptides mobilized by
      exercise may depend on the underlying diseases or pathophysiologic condition.

PMID- 9140712
TI  - Rape and rapists: theory and treatment.
AB  - The sexual assault of adult women is noteworthy by its huge social and personal
      cost to the victims, their families, and ultimately society as a whole. The past
      decade has seen burgeoning research and clinical interest regarding child
      molesters but a lack of equivalent effort concerning rapists. Rapists are
      significantly different from child molesters. While considerable heterogeneity
      exists within this group, there is a lack of distinctiveness when compared to the
      wider population of serious criminal offenders. These two features of rapists
      have implications both for research and treatment. We also argue that despite the
      advances of the last decade this has been in terms of theory proliferation rather
      than integration, and that major explanatory gaps remain. In particular, there is
      a need for more middle-level theory that articulates mechanisms and can underpin
      treatment. Current treatment approaches have typically been developed for child
      molesters, and while there has been a significant increase in comprehensiveness
      and sophistication, the evidence for treatment efficacy with rapists remains
      tentative. Treatment programs need to be tailored to the specific needs of
      rapists and to the issues of treatment engagement and completion. We conclude
      with a variety of suggestions for the research agenda over the next decade.

PMID- 9140713
TI  - Recurrent abdominal pain in children: a review of psychological factors and
      treatment.
AB  - This paper reviews current knowledge regarding recurrent abdominal pain (RAP) and
      the physiological, dietary, and psychological variables that may have some
      influence in pain episodes. Emphasis is placed on psychological factors and
      studies that have investigated psychological treatment modalities. There is some
      limited evidence of physiological dysfunction in RAP patients, and while some
      researchers have asserted that RAP may be a dietary disorder, results of several
      studies do not support this assertion. Studies examining psychological variables
      in RAP patients show elevated anxiety levels; however, elevated anxiety is also
      associated with organic abdominal pain. Psychological treatments focusing on
      cognitive-behavioral methods have demonstrated success in treating RAP. Follow-up
      studies are needed to determine the long-term success of these treatments, and
      continued research examining which children benefit from treatment would also be
      beneficial.

PMID- 9140714
TI  - Construct validity of negative symptoms: an empirical and conceptual review.
AB  - The construct validity of negative symptoms is reviewed, and findings on deficit
      negative symptoms are also incorporated. A valid negative symptom construct
      should: (a) have replicable relationships with observable phenomena and other
      constructs; (b) have good reliability, temporal stability, and homogeneity; and
      (c) predict prognosis and response to treatment, possess convergent and
      discriminant validity, and be useful to clinicians. Although a number of well
      replicated findings provide support for the validity of the construct,
      modification is warranted. Specifically, the data suggest that there is a highly
      correlated set of negative symptoms, which includes flat affect, alogia,
      anhedonia, and avolition. Primary and enduring symptoms from this set have good
      predictive and discriminant validity and can be studied in the context of the
      deficit syndrome, as well as with current negative symptom rating scales. Future
      studies should examine whether deficit negative symptoms are better
      conceptualized as a dimension or a category, elucidate the relationship between
      deficit symptoms and additional clinical and behavioral variables (e.g., response
      to newer neuroleptic medications and diminished emotional responding), and
      explore differences between the pattern of correlates of deficit symptoms and
      those of the positive and thought disorder symptoms.

PMID- 9140716
TI  - Preference, choice, and persons with disabilities: a synopsis of assessments,
      interventions, and future directions.
AB  - A recent revolution in service delivery for persons with developmental
      disabilities encompasses increased client independence and improved quality of
      life. Specifically, care providers have focused on client expressions of
      preference, choice-making, and choice availability as key elements of study in
      this new revolution. We review and critique the primary methods of assessing
      preference and choice for persons with disabilities, including interviews and
      questionnaires, pictorial presentations, technological apparati, and direct
      observation. We also provide an overview of the burgeoning literature on
      intervention programs designed to enhance choice for this population, such as
      giving more choice to clients, teaching choice-making skills, and improving staff
      member skills regarding choice availability. Finally, we provide a synopsis of
      the future directions in this area that should receive the most attention from
      researchers and caregivers.

PMID- 9140715
TI  - The gay adolescent: stressors, adaptations, and psychosocial interventions.
AB  - Social stigmatization hinders the ability of gay adolescents to achieve the tasks
      of adolescence. Because their sexual identity is denigrated by society, these
      youth have difficulty forming a positive identity and establishing healthy peer
      and intimate relationships. Family relations are often painful, and gay
      adolescents are susceptible to loneliness, isolation, depression, and suicide.
      Validation of these adolescents' affectional and erotic feelings helps to
      normalize their adolescence, as does providing them with a peer group of other
      gay youth.

PMID- 9140717
TI  - Hb T-Cambodia, a beta chain variant with the mutations of Hb E and Hb D-Punjab,
      confirmed by DNA analysis.
AB  - Hemoglobin variants with two amino acid substitutions affecting one globin chain
      are relatively rare. Hb T-Cambodia, a doubly substituted beta-globin variant, was
      characterized previously by amino acid sequencing as having sequence alterations
      in beta 26 (beta 8)Glu-->Lys and beta 121(GH4) Glu-->Gln (1). It is a variant
      that migrates cathodic to Hb A2 on alkaline electrophoresis and with Hb A on acid
      citrate agar electrophoresis. We report here the mutations of Hb T-Cambodia at
      the nucleotide level using DNA sequencing, in beta-globin gene codon 121 (GAA-
      >CAA) and in codon 26 (GAG-->AAG). These are the mutations of Hb D-Punjab and Hb
      E, respectively.

PMID- 9140718
TI  - Clinical and hematological response to hydroxyurea in a patient with Hb
      Lepore/beta-thalassemia.
AB  - The possibility of increasing Hb F in vivo using drugs like 5-azacytidine,
      hydroxyurea, and butyrate has been established. However, in many cases this does
      not entail an increase in total hemoglobin. We report on a patient with Hb
      Lepore/beta-thalassemia being treated with hydroxyurea (30 mg/Kg/day) because of
      the presence of erythroid extramedullary masses with severe neurological
      abnormalities. During therapy the patient showed a remarkable improvement in
      neurological signs due to the reduction in extra-medullary masses, a significant
      increase in both total hemoglobin (from 5.8 to 9.7 g/dl) and Hb F (from 4.9 g/dl
      to 9.1 g/dl). The marked improvement in hemoglobin level in our patient with Hb
      Lepore/beta-thalassemia suggests gamma-globin gene activation due to the DNA
      structure determined by the crossover event.

PMID- 9140719
TI  - Hb E and alpha-thalassemia; variability in the assembly of beta E chain
      containing tetramers.
AB  - The level of Hb E (including Hb A2) was quantitated in 30 adult Hb E
      heterozygotes by cation exchange high performance liquid chromatography; in 20
      subjects the alpha-globin gene status was determined by gene mapping and
      polymerase chain reaction methodology. A decrease in Hb E level was observed
      which was directly related to the type of alpha-thalassemia that was present; the
      lowest percentage of Hb E (and Hb A2) was 10.2%, seen in two persons with Hb
      Constant Spring (CS)-Hb H disease (alpha CS alpha/--). Similar analyses were made
      for several newborn babies with a Hb E heterozygosity, the Hb E level was
      determined as beta E by a reversed phase high performance liquid chromatographic
      procedure. One baby with Hb E trait and Hb H disease (-alpha/--) had a beta E
      level of 17.7% (as % of beta A + beta E) comparable to that seen for adults with
      an identical genotype. One fetus with hydrops fetalis (--/--) and Hb E trait had
      low beta E and beta A levels which, however, were nearly identical (1.5 and 1.3%
      of the total hemoglobin). These beta chains apparently combine with the embryonic
      zeta chain to form Hb Portland-II (zeta 2 beta 2A) and a variant of this
      hemoglobin (zeta 2 beta 2 E). The affinity of the two beta chains for the zeta
      chain must be the same and quite different from that for the alpha chain.
      Moreover, this single observation suggests an equal synthesis of beta A and beta
      E chains, the low level of Hb E in adult heterozygotes being primarily the result
      of a greatly decreased rate of assembly of alpha beta E dimers.

PMID- 9140720
TI  - A significant beta-thalassemia heterogeneity in the United Arab Emirates.
AB  - The Dubai Thalassemia Center has identified 35 different beta-thalassemia
      mutations in 570 chromosomes from the United Arab Emirates population using gene
      amplification, hybridization with specific labeled oligonucleotide probes,
      sequencing of amplified DNA, restriction enzymes, and amplification refractory
      mutation system techniques. This large number of mutations which represent 21% of
      the total beta-mutations discovered worldwide reflects the heterogenous nature of
      the population living in the United Arab Emirates (1). We found that 50% of our
      beta-thalassemia patients have a concomitant alpha-thalassemia; namely the -alpha
      3.7 kb deletion. Co-inheritance of alpha-thalassemia especially in the form of
      two alpha-globin gene deletions have an ameliorating effect on the phenotype
      presentation of our beta-thalassemia. Nine patients (one homozygote and eight
      compound heterozygotes) were identified with Hb Monroe (IVS-I,-1 (G-->C)), a
      thalassemic hemoglobin characterized by an Arg-->Thr substitution in codon 30 of
      the beta-globin gene. In addition, one of the patients was a compound
      heterozygote for Hb Tacoma [IVS-I, +1 (G-->C)]; a point mutation affecting the
      third nucleotide of codon 30 (G-->C) causing an Arg-->Ser replacement.

PMID- 9140721
TI  - Compound heterozygosity for Hb S and the hybrid HbS Lepore, P-Nilotic, and Kenya;
      comparison of hematological and hemoglobin composition data.

PMID- 9140722
TI  - Genetic heterogeneity of beta-thalassemia in populations of the Iberian
      Peninsula.

PMID- 9140723
TI  - Hemoglobin disorders in Macao.

PMID- 9140724
TI  - Historical and anthropological correlates of beta S haplotypes and alpha- and
      beta-thalassemia alleles in the Arabian Peninsula.

PMID- 9140726
TI  - Reactivity to tyrosinase: expression in cancer (melanoma) and autoimmunity
      (vitiligo).
AB  - Anti-tyrosinase antibodies are found in the sera of patients with diffuse
      vitiligo, metastatic melanoma and in sera of patients with melanoma and
      hypopigmentation (MAH). The autoantigen is tyrosinase itself, the enzyme that
      participates in pigment (melanin) formation by both melanocytes and melanoma
      cells. The production of autoantibodies in both diseases is associated with the
      development of white patches on the patients' skin. The presence of these
      autoantibodies in patients with melanoma may suggest a better prognosis. Cross
      antigenicity between melanoma cells and normal melanocytes is most probably the
      key mechanism leading to the appearance of MAH. Anti-tyrosinase antibodies are
      absorbed by melanocytes and by melanoma cells in all the 3 situations (melanoma,
      vitiligo, MAH). However, since the production of antibodies in vitiligo exceeds
      that in melanoma or MAH, the antibodies are detected in significantly higher
      levels only in vitiligo. It is suggested here that anti-tyrosinase antibodies may
      be responsible, or at least participate in destruction of normal melanocytes
      during the immune response to melanoma antigens. This mechanism may be
      responsible for the phenomenon of MAH in patients with melanoma, and for the
      formation of the autoimmune vitiligo. Anti-tyrosinase antibodies may serve for
      two clinical applications. One is a marker for monitoring and follow up of
      patients with melanoma treated by immune therapy. The second is active (or
      passive) immunotherapy. We have recently shown that C57BL/6J mice immunized with
      tyrosinase generated a high titer of antityrosinase antibodies, and following the
      inoculation of melanoma cells developed lower number of lung metastases, compared
      to the unvaccinated control group.

PMID- 9140725
TI  - A comparison of the performance in vitro of precision cut tissue slices and
      suspensions of human spleen with special reference to immunoglobulin and cytokine
      production.
AB  - During the past decade our knowledge of the cellular and molecular events
      associated with key immunological responses has been greatly advanced by the use
      of isolated subpopulations of immunocompetent cells, cloned cell lines and
      recombinant derived cytokines. Valuable as these studies have been they do not
      truly reflect the complex integrative events which take place in both primary and
      secondary lymphoid tissue both in vivo and in vitro. In order to address this
      problem we have developed a tissue culture procedure which is a modification of
      that previously used by others to study T cell maturation in the thymus. This
      involves culturing precision cut slices of human lymphoid tissue in a sponge
      culture system. Using this technique we have observed marked differences in both
      immunoglobulin and cytokine secretion between slices and suspensions of human
      spleen. In brief, cultured slices (mitogen stimulated or otherwise) consistently
      secrete higher levels of immunoglobulin, IL-1 beta, IL-6, IL-8 and IL-11 and
      exhibit much lower proliferation than suspensions of the same tissue. Mitogen
      stimulated suspensions on the other hand secrete higher levels of IL-2, IL-4, IL
      10 and TNF alpha than do slices. These differences are also observed at the
      intracellular cytokine level. Additional studies reveal that the immunoglobulin
      and cytokine secretion observed is largely due to the de novo synthesis of these
      molecules and not as a result of spontaneous secretion of preformed products.
      Furthermore immunoglobulin secretion in both slices and suspensions can be
      inhibited by the addition of specific antibodies to IL-1 beta, IL-6 and TNF alpha
      while IL-6 production can be differentially modulated by a variety of substances.
      Preliminary studies indicate that close interaction between B cells and stromal
      cells within explants accounts for some of the observed differences. This review
      article describes the basic technique, summarises the results we have obtained in
      this system and outlines the possible basis of the observed differences.

PMID- 9140727
TI  - Immunogenetics of human IgE.
AB  - Immunoglobulin E plays a central role in mediating the pathology of allergic
      disease. Conversely, it is involved in the normal protective immune responses
      against parasite infection. Both these biological processes depend on interaction
      between the variable regions (VH and VL) of IgE antibodies and target antigen. It
      is now feasible to investigate the molecular nature of VH regions used to encode
      IgE at the genetic level. Using this technology to analyze IgE in patients with
      asthma has revealed features which may have relevance for allergic disease.
      First, preferential choice of VH genes, with dominance of the small VH5 family,
      particularly the VH32 gene, has been found. This may implicate a B cell
      superantigen (superallergen) selectively driving the use of these genes. Second,
      VH5 genes in IgE are somatically mutated with clear hot spots of mutational
      activity. Mutational hotspots, which are a feature of the VH5 gene, are
      supplemented in IgE by ongoing mutations which may be involved in affinity
      maturation. Third, a single B cell can switch to either IgE or IgG4, with both
      variants coexisting in blood. These findings may provide clues to the mechanism
      by which IgE is generated, and suggest options for therapeutic intervention.

PMID- 9140728
TI  - Anti-gp210 antibodies in sera of patients with primary biliary cirrhosis.
      Identification of a 64 kD fragment of gp210 as a major epitope.
AB  - Patients with primary biliary cirrhosis (PBC) frequently produce autoantibodies
      against gp210, an integral glycoprotein of the nuclear pores. this protein
      consists of three main domains: a large glycosylated lumenal domain, a single
      hydrophobic transmembrane segment and a short cytoplasmic tail. It has been
      previously shown that autoantibodies from PBC patients exclusively react with the
      cytoplasmic tail when recombinant rat gp210 expressed in Escherichia coli was
      used as antigen. Using human gp210 isolated from HeLa cells we found the lumenal
      domain as the major target. The aim of this study was to further characterize the
      dominant autoepitopes of gp210. Sera from 88 patients with autoimmune liver
      disease and 20 controls were used. Gp210 protein was digested with papain or
      endoglycosidase H and then subjected to immunoblotting. Autoantibodies against
      gp210 were detected in 12 of 43 (28%) PBC patients, but in none of the autoimmune
      hepatitis and control sera. Four of 12 (33%) anti-gp210 positive sera reacted
      with a fragment consisting of the cytoplasmic tail and 8 (66%) sera targeted an
      epitope located within the large lumenal domain. Furthermore, our data show that
      antigenic determinant is restricted to the 64 kD glycosylated amino-terminal
      fragment and that carbohydrate residues are an essential part of this novel
      epitope. We suggest that antigens possessing both epitopes namely; the
      glycosylated lumenal domain and the cytoplasmic tail should be used for screening
      tests in order to detect all sera with anti-gp210 specificity.

PMID- 9140730
TI  - Factors influencing the outcome of group psychotherapy for bulimia nervosa.
AB  - OBJECTIVE: Group psychotherapy is a widely used form of treatment for bulimia
      nervosa, and many open and controlled studies have demonstrated that it is
      relatively effective. However, it is not clear what factors enhance or reduce
      that effectiveness. This review considers the potential role of a number of such
      factors. METHOD: The literature on the effectiveness of group psychotherapy was
      selected on the basis of its publication inclusion in peer-reviewed journals.
      Unpublished material was not included. Factors considered included theoretical
      orientation, therapy dose, concurrent treatment, client characteristics, and
      service characteristics. RESULTS: The research to date shows no obvious advantage
      attached to any single therapeutic orientation or to the gender of therapists.
      However, other aspects of group psychotherapy do seem to influence outcome.
      Better outcomes are associated with longer, more intensively scheduled groups and
      with the addition of other treatment components (e.g., individual work). There is
      also evidence that relatively large groups are a viable option. These conclusions
      are reasonably congruent with clients' own expressed preferences regarding
      therapy. DISCUSSION: It is suggested that future research should focus on
      matching the characteristics of individual bulimics to the nature of the group
      psychotherapy, in order to increase engagement and effectiveness while reducing
      drop-out rates.

PMID- 9140729
TI  - Humanization of an anti-human IL-6 mouse monoclonal antibody glycosylated in its
      heavy chain variable region.
AB  - Interleukin-6 (IL-6) inhibitors are good potential therapeutic agents in human
      patients, and anti-IL-6 antibodies are among the best candidates. Here, we have
      successfully humanized mouse monoclonal antibody SK2, which specifically binds to
      IL-6 and strongly inhibits IL-6 functions. Since this antibody possesses N-linked
      carbohydrates on Asn-30 of VH region, which seems to be very close to an antigen
      binding site, influence of these carbohydrates on antigen-binding was
      investigated. A biosensor study showed that the mouse SK2 Fab and its
      deglycosylated fragments had almost equal Kd (Kon/Koff), 26.8 nM (1.05 x
      10(6)/2.81 x 10(-2)) and 24.7 nM (1.28 x 10(6)/3.15 x 10(-2)), respectively.
      Furthermore, a mutant chimeric SK2 antibody, in which the N-glycosylation site
      was removed from the VH region, showed a Kd of 11 nM, almost similar to that of
      the original chimeric SK2 antibody, determined by Scatchard analysis with 125I-IL
      6. These data indicate the carbohydrates of mouse SK2 VH region do not
      significantly influence antigen-binding activity. In the next step, two versions
      of each humanized SK2 VL and VH regions were carefully designed based on the
      amino acid sequences of human REI and DAW, respectively. Only one alteration, Tyr
      to Phe, was made at position 71 in the two light chains, according to the
      canonical residue for LI. A N-glycosylation site was introduced on the two heavy
      chains, by changing Ser to Asn at position 30. All four combinations of humanized
      light and heavy chains could bind to IL-6 as well as the chimeric SK2 antibody.
      The light chain first version, however, could not efficiently inhibit IL-6
      binding to its receptor, indicating the importance of the LI loop conformation
      for the inhibitory activity of SK2 antibody. In contrast, both versions of the
      heavy chains were comparable, in yielding good humanized SK2 antibodies,
      suggesting that the glycosylation of the SK2 VH region has no influence in
      recreating a functional antigen-binding site in this humanization.

PMID- 9140731
TI  - The relationship between socioeconomic status and eating-disordered behaviors in
      a community sample of adolescent girls.
AB  - OBJECTIVE: Although previous research has demonstrated a relationship between
      socioeconomic status (SES) and weight, the research has not been consistent
      regarding the relationship between SES and eating disorders. This analysis was
      designed to examine this relationship in a large community sample of adolescent
      girls (Grades 7 to 12). METHOD: Items were selected from a comprehensive self
      report health survey completed by 17,571 adolescent girls. The relationships
      between SES and dieting behaviors and attitudes were examined using chi-square
      tests and analysis of variance (ANOVA) to control for body mass index. RESULTS:
      Although there was a significant positive relationship between SES and some of
      the unhealthy dieting behaviors, there was no relationship between self-report of
      clinically significant eating-disordered behaviors (e.g., vomiting twice a week
      or more) and SES in this community sample. DISCUSSION: This study suggests that
      while there may be a significant relationship between SES and dieting or other
      behaviors associated with eating disorders, this relationship does not apply to
      diagnostically significant behaviors. SES may be associated with differences in
      dieting or eating behaviors; however, among those young women who meet
      psychiatric criteria for an eating disorder, SES does not appear to be a
      significant factor.

PMID- 9140732
TI  - Group psychoeducation for bulimia nervosa with and without additional
      psychotherapy process sessions.
AB  - OBJECTIVE: The present study examined whether additional sessions of group
      psychotherapy process (PP) would incrementally benefit bulimia nervosa (BN)
      subjects over and above that which is achieved through a course of brief group
      psychoeducation (PE). METHOD: Utilizing a quasi-experimental design, the first
      cohort of 40 BN subjects completed five-session PE-alone groups that were highly
      didactic and explicitly devoid of group process work. The second cohort of 41 BN
      subjects completed 12-session PE + PP groups that integrated PE with more
      conventional cognitive-behavioral group process interventions. RESULTS: Both
      treatments were associated with comparable levels of change on measures of
      specific and nonspecific psychopathology. Furthermore, the two treatments did not
      differ in rates of premature termination, in rates of remission in eating
      symptoms, in rates of normalization of scores on psychometric measures, or in
      consumer evaluation of the treatments. DISCUSSION: While subjects value the
      opportunity to engage in psychotherapy process with other group members, the
      addition of seven such sessions offers no enhanced therapeutic benefit over five
      sessions of group PE.

PMID- 9140733
TI  - Drop-out and failure to engage in individual outpatient cognitive behavior
      therapy for bulimic disorders.
AB  - OBJECTIVE: It was the aim of this study to explore the characteristics of
      bulimics who fail to complete therapy. Noncompleters were divided into those who
      failed to engage and those who dropped out, so that these groups could be
      directly compared. METHOD: Participants were 50 women (bulimia nervosa or
      anorexia nervosa of the bulimic subtype) recruited from a case series of
      referrals to an eating disorders clinic, who were offered individual cognitive
      behavior therapy. The women (28 completers; 7 failure to engage; 15 drop-outs)
      were compared on standardized measures of eating, psychological, and family
      characteristics. RESULTS: The noncompleting groups both had high levels of
      borderline psychopathology and more severe perceived bulimic characteristics than
      the completers. However, the "drop-out" and "failures to engage" had very
      different patterns of perceived family emotional involvement, with the failures
      to engage reporting relatively healthy functioning. DISCUSSION: Our understanding
      of the eating disorders (and of the effectiveness of treatment) is skewed by the
      nature of the samples involved. The characteristics of noncompleters could be
      used at initial assessment to target clinical work towards lowering rates of drop
      out and failure to engage.

PMID- 9140734
TI  - The relationship between perceived evaluation of weight and treatment outcome
      among individuals with binge eating disorder.
AB  - OBJECTIVE: This study was designed to explore among individuals with binge eating
      disorder (BED) perceptions of others' evaluation of their weight-related behavior
      and affect aroused by such. METHOD: Prior to treatment for binge eating and
      weight loss, 47 subjects diagnosed with BED completed a questionnaire designed to
      assess the perceived evaluation of an understanding and a critical individual in
      both positive and negative weight-related situations and subjects' affective
      responses to being evaluated. RESULTS: Subjects exhibited characteristic patterns
      of affective response to perceived evaluation of their weight-related behavior,
      with negative situations and critical evaluators evoking greater degrees of
      negative affect. Negative affect in response to perceived evaluation was
      associated with poor outcome with weight loss but not binge eating. However, this
      finding was due to the correlation between negative affect in response to
      perceived evaluation and global severity of psychopathology (SCL-90-R).
      DISCUSSION: The results suggest that psychopathology in this population predicts
      poor outcome with weight loss, and further that independent of its relationship
      with depression, psychopathology is strongly associated with a tendency to
      experience negative affect in response to perceived evaluation by others of
      weight-related behavior.

PMID- 9140735
TI  - Effects of coping style and negative body image on eating disturbance.
AB  - OBJECTIVE: Relationships among coping strategies, negative body image, and eating
      disturbance were studied. METHOD: Subjects were 128 college women; measures
      included the Eating Attitudes Test (EAT-26), the Coping Inventory for Stressful
      Situations (CISS), and three indices of negative body image. RESULTS: Higher use
      of both emotion-oriented coping and avoidance-oriented coping via distraction was
      associated with higher EAT scores; higher use of emotion-oriented coping also was
      associated with more negative body image. Findings agree with data associating
      these coping styles with other measures of psychological distress and
      psychopathology. Task-oriented coping also was high, but unrelated to negative
      body image or eating disturbance. Hierarchical regression analysis yielded a
      significant interaction between emotion-oriented coping and negative body image:
      The higher the use of emotion-oriented coping, the less the level of negative
      body image appeared to affect EAT score. DISCUSSION: Both the main effect for
      coping and the interaction suggest that high use of emotion-oriented coping
      should be considered a risk factor for eating disturbance.

PMID- 9140736
TI  - The augmented platelet intracellular calcium response to serotonin in anorexia
      nervosa but not bulimia may be due to subsyndromal depression.
AB  - OBJECTIVE: Serotonergic dysregulation is associated with both bulimia and
      anorexia nervosa. This study attempted to measure the levels of basal and
      serotonin-stimulated intracellular calcium in patients with bulimia and anorexia
      Nervosa. METHOD: In this study, basal levels of platelet intracellular calcium as
      well as the effects of serotonin on intracellular calcium were studied using the
      Fura-2 method in subjects with bulimia (N = 11), anorexia nervosa (N = 12), and
      in matched normal controls (N = 17). Depressed patients, defined as meeting DSM
      IV criteria for major depression or having a Hamilton Depression Scale score over
      16 were excluded from the study. RESULTS: An enhanced serotonin-mediated
      mobilization of intracellular calcium was found in anorexia compared to both
      bulimics and controls at serotonin concentrations of 100 nM (p < .002), 500 nM (p
      < .001), and 1 microM (p < .001, ANOVA), respectively. However, when the anorexic
      group was subdivided into high and low Hamilton Depression scale groups, only the
      high Hamilton group demonstrated an augmented intracellular response to
      serotonin, with the low Hamilton group not differing from controls. DISCUSSION:
      These results suggest that the augmented intracellular calcium response to
      serotonin in anorexia may be due to subsyndromal depression in that group rather
      than to a primary eating disorder.

PMID- 9140737
TI  - The night eating syndrome in the general population and among postoperative
      obesity surgery patients.
AB  - OBJECTIVE: To determine the prevalence of night-eating syndrome in the general
      population and among a new sample of obesity surgery patients. METHODS: Night
      eating syndrome was defined by presence of morning anorexia, excessive evening
      eating, evening tension and/or feeling upset, and insomnia. A randomly selected
      sample of 2,097 adults (survey sample) answered structured interview questions on
      night-eating syndrome. A self-report form was completed by 111 patients who had
      received gastric restriction surgery for obesity at a patient reunion (patient
      sample). RESULTS: Prevalence of night-eating syndrome in the survey sample was
      1.5% (31 of 2,097). Prevalence in the patient sample was 27% (30 of 111). Weights
      for subjects in each sample, with and without the syndrome, were comparable.
      DISCUSSION: Prevalence of night-eating syndrome was higher in the patient sample
      than in the survey sample. Within each sample, presence of the syndrome was not
      related to weight. Prevalence in the survey sample was within the range reported
      for binge-eating disorder. Night-eating syndrome may warrant consideration as a
      distinct eating disorder.

PMID- 9140738
TI  - Persistent osteopenia after recovery from anorexia nervosa.
AB  - OBJECTIVE: Osteopenia is a known complication of anorexia nervosa. Most studies
      have focused on the features of the illness which predict bone complications. The
      few reports on recovery have been conflicting, with some studies suggesting
      restoration of normal bone mass with recovery from anorexia nervosa, while others
      suggest that the improvement may only be partial. This is the first report of
      bone density in a long-term recovered group. METHOD: We measured bone density in
      the hip and lumbar spine in 18 recovered women, using dual energy X-ray
      absorptiometry. RESULTS: We found an unexpectedly high incidence of osteopenia,
      with 14 of 18 women affected. Duration of amenorrhea was the best predictor of
      reduced bone density. An index of the duration of recovery, relating it to the
      duration of illness, was also highly correlated with outcome. DISCUSSION: Our
      findings have implications, both for the individual and for the economic burden
      to society. We suggest that the use of oral contraceptives in women recovering
      from anorexia nervosa needs further investigation. Additional longitudinal
      studies are clearly warranted.

PMID- 9140739
TI  - Skills training treatment for adaptive affect regulation in a woman with binge
      eating disorder.
AB  - This case study describes a skills training treatment for binge eating which
      focused on teaching adaptive affect regulation. A 36-year-old obese woman with a
      long history of severe binge eating received individual treatment specifically
      aimed at enhancing her emotion regulation abilities. By treatment end she no
      longer met criteria for binge eating disorder.

PMID- 9140740
TI  - Avoidance coping, binge eating, and depression: an examination of the escape
      theory of binge eating.
AB  - The relationship between binge eating, avoidance coping, and depression was
      investigated with reference to the escape theory of binge eating which predicts
      binge eaters will exhibit elevated avoidance coping. Undergraduate females were
      selected into one of three groups: control (nonrestrained/nonbinge eating) (n =
      73), restrained (restrained/ nonbinge eating) (n = 61), and binge eating
      (restrained/binge eating) (n = 15). The groups did not differ on use of avoidance
      coping. Binge eating scores were significantly correlated with avoidance coping
      and depression, but hierarchical regression analyses indicated avoidance coping
      did not significantly add to the prediction of binge eating above the
      contribution of depression. It is proposed therefore, that it is not appropriate
      to use findings of elevated avoidance coping in individuals with eating disorder
      in support of the escape theory.

PMID- 9140741
TI  - General practice consultation patterns preceding diagnosis of eating disorders.
AB  - OBJECTIVE: To see whether patients with eating disorders consult general
      practitioners more frequently than control subjects and, if so, to describe the
      pattern of consultation. METHOD: General practitioner case record review of
      patients with anorexia nervosa, bulimia nervosa, and partial syndromes referred
      to a specialist eating disorder service. RESULTS: Seventy-eight of 100 case
      records were available for analysis. Eating disorder patients consulted
      significantly more frequently than controls over 5 years prior to the diagnosis
      of the eating disorder. They presented to the general practitioners with a
      variety of symptoms including psychological, gastrointestinal, and gynecological
      complaints. DISCUSSION: The findings suggest that methods could be developed to
      enable earlier diagnosis of eating disorders in general practice. This will
      enable the earlier application of effective treatments with the prospect of
      improved outcome.

PMID- 9140742
TI  - Characteristics of interview refusers: women who decline to participate in
      interviews relating to eating.
AB  - OBJECTIVES: The aim of this study was to compare the eating habits and weight
      ranges of 27 women who refused to participate in a semistructured interview on
      eating with 25 women who agreed to participate, to determine if there were any
      systematic differences between the two groups. METHOD: The women had previously
      completed a general psychiatric interview that also included a lifetime DSM-III-R
      diagnosis of eating disorders. About 2 years after this interview, the women were
      asked to participate in an interview that would specifically examine eating
      behaviors. RESULTS: In contrast to the results of previous studies, this study
      found that there was no difference between women who refused or agreed to
      participate in an interview about eating, in terms of their eating problems or
      weight ranges. CONCLUSIONS: It seems that eating or weight problems need not be
      overrepresented in groups who refuse to participate in surveys about eating,
      thereby undermining the accuracy of prevalence rates in the general population.
      Suggestions for achieving this representation are discussed.

PMID- 9140743
TI  - Comorbid bulimia nervosa and schizophrenia.
AB  - OBJECTIVE: Despite literature citing the frequency of abnormal eating behavior in
      persons with schizophrenia, little attention has been paid to the comorbidity of
      eating disorders and schizophrenia. This case review explores the comorbidity of
      bulimia nervosa and schizophrenia and its possible clinical implications. METHOD:
      The authors present four case reports of women with rigorously diagnosed
      schizophrenia who have eating-disordered behavior. RESULTS: The first case
      describes a woman whose bulimia nervosa clearly preceded the onset of her
      schizophrenia. The second and third cases describe women who have many
      characteristics and risk factors for bulimia nervosa and whose bulimic symptoms
      significantly interact with psychotic symptoms. The fourth case describes a woman
      with bulimic behavior which is clearly responsive to psychosis. She does not have
      a history and behavioral profile of true bulimia nervosa. DISCUSSION: These case
      reports extend support to a model that schizophrenia and bulimia may coexist in a
      complex, interactive fashion with important clinical implications.

PMID- 9140745
TI  - An experimental study of embolic effect according to infusion rate and
      concentration of suspension in transarterial particulate embolization.
AB  - RATIONALE AND OBJECTIVES: The authors evaluate the embolic effect according to
      infusion rate and concentration of particulate suspension, focusing on arterial
      occlusion level. METHODS: The renal arteries of 14 rabbits were embolized with
      150 to 250 microns polyvinyl alcohol (PVA) particles, divided into four groups
      according to two different infusion rates (1 mg/second and 0.1 mg/second) and two
      different concentrations of suspension (10 mg/mL and 2.5 mg/mL). Arteriograms
      obtained immediately and a week after embolization were assessed for occlusion
      level. For the nephrograms obtained a week after embolization, the opacifying
      areas were graded from 0 to 4. Median coronal sections of each kidney specimen
      were investigated for the presence of peripheral infarct grossly and for the
      presence of PVA particles in the small artery microscopically. RESULTS:
      Arteriograms showed various occlusion levels. Using a 0 to 4 grading system, the
      opacifying area of the nephrogram obtained 1 week after embolization was noted to
      be smaller in the low infusion rate group (P < 0.05). In gross and microscopic
      pathologic examination, the number of cases with peripheral infarct or PVA
      particles in the small artery (< 300 microns) was greater in the group with the
      low infusion rate and low concentration (P < 0.05). CONCLUSIONS: In transarterial
      particulate embolization, slower infusion of more diluted suspension provides for
      a more distal arterial occlusion.

PMID- 9140744
TI  - Influence of contrast media on blood coagulation.
AB  - RATIONALE AND OBJECTIVES: Contrast agents have been reported to influence the
      blood clotting system to an extent depending mainly on whether the compounds are
      ionic or nonionic. The objective of the current series of studies was to
      determine interspecies differences; the effect of variable incubation times; and
      the effect on thromboplastin times (TPT) of adding heparin to a number of x-ray
      and magnetic resonance imaging (MRI) contrast agents. In addition, the stability
      of clots formed in the presence of iopromide was studied. In a final experiment,
      the effect of the contrast agents on the bleeding time was studied in rats.
      METHODS: Nine x-ray and three MRI contrast agents were used in the study.
      Thromboplastin times was determined in platelet-poor plasma of humans, rats,
      rabbits, or dogs using calcium (Ca) thromboplastin from human placenta or rabbit
      brain and lung tissue and incubation times as long as 4 hours. Bleeding times
      were determined in rats 5 minutes, 4 hours, 24 hours, and 48 hours after
      intravenous injection of the contrast agents by making a small incision into the
      tail of the animal, immersing the tail in saline, and measuring the time period
      during which small blood streaks were visible. RESULTS: Nonionic contrast agents
      (x-ray and MRI) increased the TPT by a factor of 1.5 to 2, whereas ionic
      compounds prolonged TPT by a factor of > 3. Thromboplastin times increased in the
      order of dog < rabbit < rat < human 2- to 4-fold. However, the ranking of
      different contrast agents remained unchanged. Prolongation of bleeding time
      lasted as long as 24 hours for some contrast agents. Clots formed in the presence
      of iopromide were unstable and did not absorb the contrast agent. CONCLUSIONS:
      The animal models used in the current series of studies seem to be valid for
      predicting the effect of contrast agents on the blood clotting system in humans.

PMID- 9140746
TI  - Assessment of the preferred plane and sequence in the depiction of mesial
      temporal sclerosis using magnetic resonance imaging.
AB  - RATIONALE AND OBJECTIVES: Definition of optimal magnetic resonance (MR) scanning
      plane and conventional MR sequence for the detection of mesial temporal sclerosis
      (MTS). METHODS: Coronal and axial T2-weighted images and axial T2-weighted images
      parallel to the long axis of the hippocampus (APLAH) and coronal inversion
      recovery (IR) images were obtained in patients with medically intractable
      temporal lobe epilepsy in their phase 1 preoperative evaluation. Thirty-three
      consecutive MR scans were reviewed by a panel of three radiologists. Twenty-three
      patients had MR abnormalities consistent with MTS, and ten scans were normal. To
      assess the best single scanning technique, another group of three radiologists,
      who were masked to all patient data, individually assessed the different planes
      and sequences of the 33 studies presented separately in a random fashion. For
      each plane and sequence, the likelihood (L) ratio for the correct diagnosis was
      determined separately. RESULTS: For all planes considered separately, a
      likelihood ratio of 4.4 was optimal for the coronal T2-weighted images. The
      likelihood ratio of APLAH T2 was 2.2; of axial T2, 3.9; of coronal IR, indefinite
      because of 100% specificity. CONCLUSIONS: For the assessment of MTS, coronal T2
      weighted images were considered the best single scanning technique.

PMID- 9140747
TI  - Specimen mammography-guided fine-needle aspirates of clinically occult benign and
      malignant lesions. Analysis of cell number and type.
AB  - RATIONALE AND OBJECTIVES: The authors determine the cell counts and percentages
      of epithelial cells in fine-needle aspirates (FNA) of mammographically detected
      breast lesions. METHODS: Specimen mammography-guided 20-gauge fine-needle
      aspirations were performed on 151 consecutive lesions. Cell counts were
      determined by flow cytometry of 106 consecutive aspirates. Semiquantitative
      determination of the percentage of epithelial cells was done by cytologic
      analysis of 151 aspirates. RESULTS: Single FNA cell counts were greater than 1000
      for all lesions and greater than 7000 in 57% (31 of 54) of malignant and 35% (18
      of 52) of benign lesions, P = 0.02. Fine-needle aspirates of soft tissue
      abnormalities had more than 7000 cells in 59% (27 of 46) of specimens, compared
      with 36% (22 of 61) in calcifications, P < 0.05. With the exception of
      fibroadenomas, the mammographic appearance of benign lesions, lesion size, and
      patient age had no association with cell counts. Ninety-three percent (76 of 82)
      of malignant lesion FNA and 80% (55 of 69) of benign lesion FNA had 50% or
      greater epithelial cells, P < 0.05. CONCLUSIONS: Fine-needle aspiration yields
      abundant cell counts of predominantly epithelial cells from most types of
      mammographically detected lesions and should be considered as a source of fresh
      cell samples for the study of benign and early malignant breast disease.

PMID- 9140748
TI  - Superparamagnetic iron oxide enhanced magnetic resonance imaging of rat liver
      with hepatocellular carcinoma and benign hyperplastic nodule.
AB  - RATIONALE AND OBJECTIVES: The authors assess the potential of a new
      superparamagnetic iron oxide (SPIO) in grading hepatocellular carcinoma (HCC)
      histologically and in differentiating HCC from benign hyperplastic nodule (HPN).
      METHODS: Nine Wistar rats (with poorly to moderately differentiated HCC, well
      differentiated HCC, and HPN) received drinking water containing N
      nitrosomorpholine, and were examined by magnetic resonance imaging (4.7 tesla).
      Spin-echo images (repetition time/echo time, 600/24.5 mseconds) were obtained
      before and 15 minutes after intravenous administration of 10 mumol Fe/kg of SH U
      555A. RESULTS: Poorly to moderately differentiated and well-differentiated HCC
      showed no significant change in signal-to-noise ratio (SNR) 15 minutes after
      contrast, whereas HPN showed a significant decrease in SNR. The contrast-to-noise
      ratio (CNR) between each kind of tumor and adjacent liver parenchyma showed a
      significant increase at 15 minutes after contrast. CONCLUSIONS: The SPIO
      discussed in this article may help to differentiate HCC from HPN, but it remains
      difficult to grade hepatocellular carcinoma histologically.

PMID- 9140749
TI  - Alterations of lactate (+lipid) concentration in brain tumors with in vivo
      hydrogen magnetic resonance spectroscopy during radiotherapy.
AB  - RATIONALE AND OBJECTIVES: The authors determine whether assessment of the
      relative lactate(+lipid) concentration ([r-Lac(+lip)]) obtained from hydrogen
      magnetic resonance (MR) spectroscopy is useful for predicting the outcome of
      radiotherapy on brain tumors. METHODS: Fifty-one hydrogen MR spectroscopic
      studies were performed in eight patients with primary or metastatic brain tumor
      before and during radiotherapy. The r-Lac(+lip) calculated as the ratio of
      lactate(+lipid) peak area to total water was compared before and during
      radiotherapy in each case. The change of tumor volume measured on magnetic
      resonance images also was compared. RESULTS: The r-Lac(+lip) substantially
      decreased in the radiosensitive cases (three lymphomas and one brain cancer) but
      did not decrease, even at the end of therapy, in the radioresistant cases (two
      brain cancers and two glioblastomas). CONCLUSION: Assessment of r-Lac(+lip) may
      adjunctively contribute to the early prediction of the radiotherapeutic effect on
      brain tumors.

PMID- 9140750
TI  - Auditory cortex activation in deaf subjects during cochlear electrical
      stimulation. Evaluation by functional magnetic resonance imaging.
AB  - RATIONALE AND OBJECTIVES: The authors detect activation in the auditory cortex
      during cochlear electrical stimulation in deaf patients using functional magnetic
      resonance (MR) imaging. METHODS: Stimulating electrode was inserted gently under
      local anesthesia close to the round window membrane of the cochlea in seven
      cochlear implant candidates. These patients suffered from postlingual-acquired
      deafness. Four patients were stimulated above the electrical perception threshold
      and three below the electrical discomfort threshold. Functional scans (fast low
      angle shot 91 mseconds/60 mseconds) were acquired in an oblique axial plane
      running parallel to the sylvian fissure. Four consecutive series of six images
      were obtained in 6 minutes. The acquisition time of each image was 15 seconds.
      RESULTS: During electrical cochlear stimulation below the discomfort threshold,
      the three patients described "auditory" sensations with activation of the
      superior temporal regions. In two patients with electrical stimulation of the
      left ear, the maximum signal intensity increased by 8.42% in the right auditory
      cortex and 5.69% in the left. In one patient with a right electrical stimulation
      only the left cortex was activated. Electrical cochlear stimulation above the
      perception threshold induces no significant activation in the auditory cortex.
      CONCLUSION: Functioning MR imaging can detect activation in the auditory cortex
      during cochlear electrical stimulation in deaf patients using a conventional 1.5
      tesla system in a routine hospital environment. Further studies are needed to
      investigate its usefulness in clinical practice.

PMID- 9140751
TI  - Correlation between bone scan findings and collagenase activities in patients
      with breast cancer.
AB  - RATIONALE AND OBJECTIVES: This study correlates nuclear bone scan findings and
      measurements of type IV collagenases for the evaluation of bony metastasis in
      patients with proven breast cancer. METHODS: The authors retrospectively
      evaluated the final diagnosis of a bone scan and the results of an
      immunohistochemical staining for 92 kDa and 72 kDa type IV collagenases in,
      respectively, 30 and 30 patients with metastatic breast cancer, and,
      respectively, 27 and 26 patients with primary breast cancer. The
      immunohistochemical staining was performed with tissue specimens obtained from a
      primary or metastatic breast tumor lesion. The amounts of the enzyme were graded
      from 0 to 4 and scored by multiplication with the percentage of tumor cells. The
      confidence of bone scan interpretation also was scored from 1 to 5 with
      increasing probability. RESULTS: There was a significant difference in enzyme
      scores between patients with and without metastases. Patients with < 170 92 kDa
      (26 of 27), 72 kDa (26 of 26) type IV collagenase, showed no active bony, lung,
      or liver metastases. However, there were variable bone scan findings in patients
      with a > 200 enzyme score. CONCLUSIONS: Bone scan provides no additional benefit
      in breast cancer patients with a type IV collagenase score of < 170. A bone scan
      is necessary to confirm, localize, or followup bony metastases in patients with
      an enzyme score of > 200.

PMID- 9140752
TI  - Contrast-enhanced radiography by differential absorption, using a laser-produced
      x-ray source.
AB  - RATIONALE AND OBJECTIVES: The authors evaluate the feasibility of differential
      imaging of contrast media, with division of individual pixel values obtained from
      digital images generated by characteristic radiation from a laser-produced
      plasma, bridging the K-absorption edge of the contrast agent. METHODS: Laser
      pulses from an ultrashort-pulse terawatt laser system were focused onto
      gadolinium and tantalum targets, creating a plasma from which characteristic
      radiation and Bremsstrahlung was emitted. The elements of the target were
      selected so the characteristic emission lines of one of the elements were below
      the K edge of the contrast agent and the emission lines of the other element
      above. A phantom with gadolinium and other elements in various concentrations was
      examined. One radiographic exposure was made using a gadolinium target source and
      a subsequent exposure using a tantalum source. Both images were recorded
      digitally and the transmission ratios calculated by division of the individual
      pixel values. RESULTS: When viewed separately, the two images of the test phantom
      appeared similar. In the differential image, only the gadolinium solutions were
      bright, reflecting a difference in attenuation between the two exposures.
      CONCLUSIONS: Element-specific radiographs can be obtained by differential
      imaging. When fully explored, the technique may allow for contrast-enhanced
      radiography with increased sensitivity and decreased contrast dose.

PMID- 9140753
TI  - Evaluation of D-amino acid levels in rat by gas chromatography-selected ion
      monitoring mass spectrometry: no evidence for subacute toxicity of orally fed D
      proline and D-aspartic acid.
AB  - Sprague-Dawley rats received deionized water (controls) during 28 days or
      drinking water with added D-proline, L-proline, D-aspartic acid or L-aspartic
      acid corresponding to a mean daily load of approximately 50 mg amino acid
      enantiomer kg-1 body weight. Parameters indicating the physiological status (food
      intake and body weight, glutamic-oxalic-transaminase, glutamic-pyruvic
      transaminase, alkaline phosphatase, urea and creatinine in serum, and creatine
      and osmomolality of urine) were determined. After 28 days the weights of the
      supposed target organs of toxicity (kidney, liver, brain, thymus) were determined
      and organs were inspected for macroscopic and microscopic alterations. No
      pathological changes in the organs were observed and no signs of subacute
      toxicity (liver, kidney) were found. In serum, homogenates of liver, kidney and
      brain, and in part, in urine, the amounts of D-amino acids (D-AAs) were
      quantitatively determined using chiral phase capillary gas chromatography
      selected ion monitoring mass spectrometry. Significant levels of certain D-AAs
      (Ala, Pro, Ser, Asx, Glx, Orn and Lys) were already detectable in kidney and
      liver homogenates and serum of controls. In brain homogenates the highest amounts
      among the D-AAs were found for D-Ser (up to 382 nmol g-1), moderate amounts for D
      Ala, D-Asx and D-Glx, and, in a few cases, trace amounts for D-Orn and D-Lys (1-2
      nmol g-1). D-Pro was not detected either in the brains of controls or in the
      brains of animals loaded with D-Pro. Feeding with D-Pro resulted in a 20-30 fold
      increased renal excretion of D-Pro at the end of the experiment. Continuous
      feeding with D-Asp did not increase renal excretion of this enantiomer, but in
      the serum, higher amounts (0.8-4.0 mumol-1) were determined in comparison to the
      control group (0.3-0.9 mumol-1). Feeding with D-Pro led to an increase of this
      enantiomer in serum (1.3-10.5 mumol-1). Feeding with D-Asp did not increase its
      amounts in brain homogenates (38 and 43 nmol g-1) in comparison to controls.

PMID- 9140754
TI  - Determination of fetal bile acids in biological fluids from neonates by gas
      chromatography-negative ion chemical ionization mass spectrometry.
AB  - A method has been developed for microanalysis of fetal bile acids in biological
      fluids from neonates by capillary gas chromatography-mass spectrometry using
      negative-ion chemical ionization of pentafluorobenzyl ester-dimethylethylsilyl
      ether derivatives of bile acids. Calibration curves for the bile acid derivatives
      are useful over the range 0.1-100 pg and the detection limit for bile acids was 1
      fg (S/N = 5) using isobutane as a reagent gas. Recoveries of the bile acids and
      their glycine and taurine conjugates from bile acid-free serum and dried blood
      discs ranged from 92 to 101% and from 93 to 108%, respectively, of the added
      amounts of their standard samples. The analysis of bile acids on a dried blood
      disc, meconium and urine from infants, exhibited significant hydroxylation at the
      1 beta-, 2 beta-, 4 beta- and 6 alpha-positions of the usual bile acids, cholic
      and chenodeoxycholic acids, for the urinary or fecal excretion of bile acids in
      the fetal and neonatal periods. The present method was applied clinically to
      analyze bile acids on a dried blood disc from neonatal patients with congenital
      biliary atresia and hyper-bile-acidemia.

PMID- 9140755
TI  - Improved method for the estimation of hydroxyl free radical levels in vivo based
      on liquid chromatography with electrochemical detection.
AB  - Free radical damage to proteins, lipids, DNA and RNA has been thought to play an
      important role in many diseases as well as the aging process. One free radical,
      the hydroxyl free radical (HFR), is extremely reactive and is difficult to
      measure directly. HFRs were quantified by measuring the hydroxylation products
      2,3- and 2,5-dihydroxybenzoic acids (DHBAs) formed as a result of the reaction
      between HFR and systemically administered salicylate (SAL). DHBAs and SAL
      concentrations were determined using RP-HPLC with dual coulometric electrode
      detection. The method has limits of detection of 1 pg for the DHBAs and 100 pg
      for SAL (signal-to-noise ratio 3:1). A detailed interference study as well as
      analyte stability and linearity studies were performed. This method was used to
      determine basal ratios of DHBA/SAL in a variety of tissues and to study the
      effects of glutamatergic and dopaminergic drugs on DHBA/SAL ratios in brain
      region homogenates.

PMID- 9140756
TI  - Strategies for the depyrogenation of contaminated immunoglobulin G solutions by
      histidine-immobilized hollow fiber membrane.
AB  - The depyrogenation of different IgG solutions using the histidine-linked hollow
      fiber membrane developed in our laboratory is presented here. Three strategies
      for endotoxin (ET) removal were investigated according to the immobilized
      histidine's ability to bind different immunoglobulins: (1) ET removal from 1
      mg/ml non histidine-binding mouse monoclonal IgG1 (MabCD4) solution was achieved
      in the presence of acetate buffer (pH 5.0) without any protein loss. (2) For
      contaminated human IgG, combined adsorption of ET and IgG in the presence of MOPS
      of Tris buffer was tested, followed by differential elution using increasing salt
      concentrations. This attempt was not successful since ET were quantitatively
      found in the IgG elution fraction. (3) Alternatively, it was proposed to adsorb
      selectively ET in the presence of acetate buffer (pH 5.0) under non binding
      conditions for human IgG. Human IgG could then be purified if necessary with the
      same membrane in the presence of MOPS buffer (pH 6.5). With a 1 m2 histidine-PEVA
      module under these operating conditions, it is estimated that the depyrogenation
      of 3 l of 1 mg/ml IgG (human or murine) solution containing 80 EU/ml of ET should
      be possible.

PMID- 9140757
TI  - Quantitative high-performance liquid chromatographic determination of retinoids
      in human serum using on-line solid-phase extraction and column switching.
      Determination of 9-cis-retinoic acid, 13-cis-retinoic acid, all-trans-retinoic
      acid, 4-oxo-all-trans-retinoicacid and 4-oxo-13-cis-retinoic acid.
AB  - A fully automated isocratic high-performance liquid chromatographic method for
      the determination of 9-cis-retinoic acid, 13-cis-retinoic acid, all-trans
      retinoic acid, 4-oxo-13-cis-retinoic acid and 4-oxo-all-trans-retinoic acid, has
      been developed using on-line solid-phase extraction and a column switching
      technique allowing clean-up and pre-concentration in a single step. A 500
      microliter sample of serum was diluted with 750 microliters of a solution
      containing 20% acetonitrile and the internal standard 9,10-dimethylanthracene.
      About 1000 microliters of this mixture was injected on a 20 x 4.6 mm I.D. poly
      ether ether ketone (PEEK) pre-column with titanium frits packed with Bondapak
      C18, 37-53 microns, 300 A particles. Proteins and very polar compounds were
      washed out to waste, from the pre-column, with 0.05% trifluoroacetic acid (TFA)
      acetonitrile (8.5:1.5, v/v). More than 200 aliquots of diluted serum could be
      injected on this pre-column before elevated back-pressure enforces replacement.
      Components retained on the pre-column were backflushed to the analytical column
      for separation and detection at 360 nm. Baseline separation was achieved using a
      single 250 x 4.6 mm I.D. Suplex pKb-100 column and a mobile phase containing
      69:10:2:16:3 (v/v) of acetonitrile-methanol-n-butanol-2% ammonium acetate-glacial
      acetic acid. A total time of analysis of less than 30 min, including sample
      preparation, was achieved. Recoveries were in the range of 79-86%. The limit of
      detection was 1-7 ng/ml serum and the precision, in the concentration range 20
      1000 ng/ml, was between 1.3 and 4.5% for all five compounds. The method was
      applied for the analysis of human serum after oral administration of 60 mg
      Roaccutan. The method is well suited for pharmacological studies, while the
      endogenous levels of some retinoic acid isomers are below the limit of
      quantitation.

PMID- 9140758
TI  - Concurrent quantification of cellular cholesterol, cholesteryl esters and
      triglycerides in small biological samples. Reevaluation of thin layer
      chromatography using laser densitometry.
AB  - Absolute specificity and high accuracy is required for the quantitation of
      cholesterol, cholesteryl esters and triglycerides in small biological samples,
      particularly in a limited number of cells. Both can be achieved through thin
      layer chromatography and molybdatophosphoric acid staining, while the
      shortcomings of traditional spot detection are overcome by laser densitometry.
      The major advantage of the proposed technique is the concurrent assay of nanogram
      quantities of cholesterol, cholesteryl esters and triglycerides. Our assay is at
      least ten-fold more sensitive than common thin-layer chromatography-based
      techniques and at least four-fold more sensitive than common enzymatic methods.
      The present low-cost assay is highly reproducible and may be particularly
      suitable for the routine lipid analysis of a 10% aliquot of relatively small
      tissue and cell samples, equivalent, for instance, to > or = 10(4) human
      monocytes.

PMID- 9140759
TI  - Optimization of the capillary zone electrophoresis loading limit and resolution
      of proteins, using triethylamine, ammonium formate and acidic pH.
AB  - Capillary zone electrophoresis (CZE) of five model proteins (lysozyme, myoglobin,
      ribonuclease A, alpha-lactalbumin, and trypsinogen), using ammonium formate as
      the electrophoretic buffer and triethylamine (TEA) as a buffer additive at pH
      2.5, was used for protein separation. The electrophoretic behavior of these
      proteins was examined with respect to various concentrations (10-40 mM) of TEA
      and of ammonium formate. Based on the experimental parameters of electrophoretic
      resolution, current, and peak separation time, an electrolyte (30 mM each of TEA
      and ammonium formate) was empirically derived as the optimum for scale-up
      separation. The loading limit for proteins, covering a wide range of injection
      volumes (60-990 nl) and amount of protein (1-21 pmol of each protein), was
      investigated on 75 and 100 microns I.D. untreated fused-silica capillaries.
      Protein adsorption (average < 15%) was experimentally determined using this
      volatile buffer system.

PMID- 9140760
TI  - Picogram determination of a novel dopamine D4 receptor antagonist in human plasma
      and urine by liquid chromatography with atmospheric pressure chemical ionization
      tandem mass spectrometry.
AB  - A sensitive and specific assay for the determination of 3-[[4-(4
      chlorophenyl)piperazin-1-yl]methyl]-1H-pyrrolo[2,3-b]p yri dine (I, L-745,870), a
      potential antipsychotic agent, has been developed, utilizing high-performance
      liquid chromatography (HPLC) with tandem mass spectrometric (MS-MS) detection.
      The analyte and the internal standard (II, 3-[[4-(4-trifluoromethyl)piperazin-1
      yl]methyl]-1H-pyrrolo[2,3-b] pyridine) were isolated from a basified biological
      matrix using liquid-liquid extraction with methyl-tert.-butyl ether. The organic
      extract was evaporated to dryness, the residue was reconstituted in a mobile
      phase and injected into the HPLC system. The chromatographic conditions used for
      the analysis were a Keystone Scientific C18 BDS 150 x 4.6 mm, 5 microns column
      with a mobile phase consisting of a 40:60 (v/v) mixture of acetonitrile and water
      containing 10 mM ammonium acetate and 0.1% formic acid pumped at a flow-rate of
      1.2 ml/min, yielding retention times of 3.4 and 5.0 min for I and II,
      respectively. The MS-MS detection was performed on a PE Sciex API III Plus tandem
      mass spectrometer using a heated nebulizer interface. Multiple reaction
      monitoring using the parent-->product ion combinations of m/z 327-->131 and 361-
      >131 were utilized to quantitate I and II, respectively. The assays were
      validated in the concentration range of 0.1 to 100 and 0.5 to 500 ng/ml for
      plasma and urine, respectively. The precision of the assays, expressed as
      coefficients of variation were less than 10% over the entire concentration range,
      with adequate assay accuracy, sensitivity and specificity to determine the
      pharmacokinetics in human subjects following a single 1-mg dose.

PMID- 9140761
TI  - Determination of the furazolidone metabolite, 3-amino-2-oxazolidinone, in porcine
      tissues using liquid chromatography-thermospray mass spectrometry and the
      occurrence of residues in pigs produced in Northern Ireland.
AB  - A method is presented for the detection of the furazolidone metabolite, 3-amino-2
      oxazolidinone (AOZ), in porcine tissue. Bound and extractable residues are
      detected following methanol-water homogenisation, repeated solvent washing and
      derivatisation with 2-nitrobenzaldehyde. Samples are analysed by using
      thermospray mass spectrometry-liquid chromatography, monitoring the positive ion
      m/z 253 with filament-assisted ionisation. There is no interference from tissue
      matrices or excess 2-nitrobenzaldehyde reagent. The limit of determination for
      liver and muscle is 10 ng/g. Recoveries are greater than 80%. The assay was used
      to investigate the occurrence of furazolidone residues in pigs from Northern
      Ireland. One hundred samples were analysed. Seventeen of these contained bound
      AOZ residues. The stability of tissue samples post mortem was investigated in
      order to achieve optimum storage conditions for samples. When liver was stored at
      4 degrees C, the concentration of bound AOZ decreased by 22% within 48 h.
      However, there were no significant changes in AOZ concentrations in liver that
      was stored at -20 degrees C for six months.

PMID- 9140762
TI  - Determination of S-1 (combined drug of tegafur, 5-chloro-2,4-dihydroxypyridine
      and potassium oxonate) and 5-fluorouracil in human plasma and urine using high
      performance liquid chromatography and gas chromatography-negative ion chemical
      ionization mass spectrometry.
AB  - A high-performance liquid chromatography (HPLC) and gas chromatography-negative
      ion chemical ionization mass spectrometry (GC-NICI-MS) method was developed for
      the analysis of the combined antitumor drug S-1 (tegafur, 5-chloro-2,4
      dihydroxypyridine and potassium oxonate) and active metabolite 5-fluorouracil in
      human plasma and urine. Tegafur was fractionated from biological fluids by
      extraction with dichloromethane and analyzed by HPLC. 5-Fluorouracil and 5-chloro
      2,4-dihydroxypyridine were extracted with ethyl acetate from the residual layer
      after extraction of tegafur, and converted to pentafluorobenzyl (PFB)
      derivatives. Potassium oxonate was cleaned up with an anion-exchange column (Bond
      Elut NH2). The extracted potassium oxonate was degraded to 5-azauracil and
      converted to PFB derivatives. The PFB derivatives were analyzed by GC-NICI-MS. A
      stable isotope was employed as the internal standard in the GC-NICI-MS analysis.
      The limits of quantitation of tegafur, 5-fluorouracil, 5-chloro-2,4
      dihydroxypyridine and potassium oxonate in plasma were 10, 1, 2 and 1 ng/ml,
      respectively. The reproducibility of the analytical method according to the
      statistical coefficients is approximately 10%. The accuracy of the method is
      good; that is, the relative error is < 10%. The methods were applied to
      pharmacokinetic studies of S-1 in patients.

PMID- 9140763
TI  - High-performance liquid chromatographic method for an automated determination of
      local anaesthetics in human plasma.
AB  - A method is described that allows the rapid and precise determination of the
      local anaesthetics bupivacaine and etidocaine from biological fluids. This method
      uses a fully automated system with solid-phase extraction in combination with a
      column-switching technique. Both sample extraction on a LiChrocart pre-column and
      elution onto the analytical LiChrospher column, were performed automatically and
      concomitantly using conventional HPLC equipment in conjunction with an OSP-2 on
      line sample preparator from Merck combined with UV detection. Recoveries were
      found to be 96.7 and 96.4% for 2 micrograms/ml bupivacaine and etidocaine,
      respectively. Lower limits of quantification were found to be 0.05 microgram/ml
      plasma for both of the compounds.

PMID- 9140764
TI  - High-performance liquid chromatographic analysis of phenobarbital and
      phenobarbital metabolites in human urine.
AB  - A HPLC assay using UV detection and post-column alkalinization was developed to
      quantify possible urinary excretion products of phenobarbital in human urine.
      After filtration the urine was injected directly onto the HPLC column for
      analysis of phenobarbital, p-hydroxyphenobarbital, phenobarbital N-glucosides and
      phenobarbital N-glucuronides. The accuracy and precision of the assay were within
      +/- 15% and the limit of detection (LOD) was 1 microM, suitable for
      pharmacokinetic studies. Phenobarbital was administered orally to five male
      subjects and urine was collected for a period of 96-108 h. Phenobarbital, p
      hydroxyphenobarbital, and phenobarbital N-glucosides were detected and quantified
      in the urine of all five subjects. The phenobarbital N-glucuronides were not
      detected in the urine. This assay provides a rapid method with improved
      selectivity to analyze urine for phenobarbital and its metabolites.

PMID- 9140765
TI  - Simultaneous measurement of serotonin and paroxetine in rat brain microdialysate
      by a single-pump column-switching technique.
AB  - Simultaneous quantitation of paroxetine and serotonin in rat brain microdialysate
      is presented as a means to study the neuropharmacokinetics and
      neuropharmacodynamics of paroxetine, a selective serotonin reuptake inhibitor. In
      order to achieve this objective, a single-pump column-switching technique was
      developed. Optimization of the mobile phase in terms of the concentration of ion
      pairing agent, pH of mobile phase, temperature of the stationary phase and
      concentration of organic modifier was investigated and a single mobile phase was
      developed for both separations. The design was such that the switching valve
      employed column I (50 mm length) and column II (250 mm length) in series in
      position A. At 15.3 min, the valve was switched to position B, in which the flow
      of the mobile phase was directed only through the short column (column I). A flow
      gradient program was used to increase the flow-rate from 0.125 ml/min to 0.4
      ml/min, which enabled a reduction in total analysis time to less than 20 min. The
      limits of detection for serotonin and paroxetine were 6 fmol and 300 fmol,
      respectively. The accuracy of the method demonstrated percent differences from
      spiked samples that were within 12.5% and the precision was found to be within
      10% R.S.D.

PMID- 9140766
TI  - Stereoselective and simultaneous measurement of cis- and trans-isomers of doxepin
      and N-desmethyldoxepin in plasma or urine by high-performance liquid
      chromatography.
AB  - Doxepin is a tricyclic antidepressant marketed as an irrational mixture of cis-
      and trans-geometric isomers in the ratio of 15:85. A convenient high-performance
      liquid chromatographic (HPLC) procedure for simultaneous quantitation of
      geometric isomers of doxepin and N-desmethyldoxepin in plasma and urine is
      described. The HPLC procedure employed a normal phase system with a silica column
      and a mobile phase consisting of hexane-methanol-nonylamine (95:5:0.3, v/v/v), a
      UV detector and nortriptyline as the internal standard. The liquid-liquid
      extraction solvent was a mixture of n-pentane-isopropanol (95:5, v/v). The limit
      of quantitation was 1 ng/ml for each isomer. The calibration curves were linear
      over the ranges 1-200 ng/ml (plasma) and 1-400 ng/ml (urine). In plasma, the
      accuracy (mean +/- S.D.) (97.53 +/- 1.67%) and precision (3.89 +/- 1.65%) data
      for trans-doxepin were similar to corresponding values for urine, i.e., 97.10 +/-
      2.40 and 3.82 +/- 1.14%. Accuracy and precision data for trans-N-desmethyldoxepin
      in plasma were 97.57 +/- 2.06 and 4.38 +/- 3.24%, and in urine were 97.64 +/-
      3.32 and 5.26 +/- 1.83%, respectively. Stability tests under three different
      conditions of storage indicated no evidence of degradation. The recovery of
      doxepin was 61-64% from plasma and 63-68% from urine. The method has been applied
      to analyses of plasma and urine samples from human volunteers and animals dosed
      with doxepin.

PMID- 9140767
TI  - New micromethod for the determination of lamotrigine in human plasma by high
      performance liquid chromatography.
AB  - An extraction procedure and reversed-phase high-performance liquid
      chromatographic assay is described and validated for the determination of
      lamotrigine in human plasma. The method involves extraction with chloroform
      isopropanol after alkalinization with a carbonate buffer, back-extraction into
      0.05% phosphoric acid and separation by reversed-phase HPLC using a 5-micron
      Supelco diphenyl column (150 x 4.6 mm I.D.). Quantitation was performed by
      measurement of the UV absorbance at a wavelength of 265 nm. This method was
      carried out on 50-200 microliters samples of plasma, depending on whether they
      were pediatric or adult samples. The lower limit of quantitation was 0.2
      microgram/ml using 200 microliters of plasma. A linear response was tested from
      0.5 to 20 micrograms/ml. Within- and between-day accuracy and precision were
      always below 10.0% at all analysed concentrations. The method selectivity towards
      the most used antiepileptic drugs has been proven. Satisfactory performances were
      obtained in the evaluation of samples from epileptic patients.

PMID- 9140768
TI  - Determination of artemether and its metabolite, dihydroartemisinin, in plasma by
      high-performance liquid chromatography and electrochemical detection in the
      reductive mode.
AB  - An analytical method for the determination of artemether (A) and its metabolite
      dihydroartemisinin (DHA) in human plasma has been developed and validated. The
      method is based on high-performance liquid chromatography (HPLC) and
      electrochemical detection in the reductive mode. A, DHA and artemisinin, the
      internal standard (I.S.), were extracted from plasma (1 ml) with 1-chlorobutane
      isooctane (55:45, v/v). The solvent was transferred, evaporated to dryness under
      nitrogen and the residue dissolved in 600 microliters of water-ethyl alcohol
      (50:50, v/v). Chromatography was performed on a Nova-Pak CN, 4 microns analytical
      column (150 mm x 3.9 mm I.D.) at 35 degrees C. The mobile phase consisted of pH 5
      acetate-acetonitrile (85:15, v/v) at a flow-rate of 1 ml/min. The analytes were
      detected by electrochemical detection in the reductive mode at a potential of 
      1.0 V. Intra-day accuracy and precision were assessed from the relative
      recoveries (found concentration in % of the nominal value) of spiked samples
      analysed on the same day (concentration range 10.9 to 202 ng/ml of A and 11.2 to
      206 ng/ml of DHA in plasma). The mean recoveries over the entire concentration
      range were from 96 to 100% for A with C.V. from 6 to 13%, from 92% to 100% for
      DHA (alpha-tautomer) with C.V. from 4 to 16%. For A, the mean recovery was 96% at
      the limit of quantitation (LOQ) of 10.9 ng/ml with a C.V. of 13%. For DHA, the
      mean recovery was 100% at the LOQ of 11.2 ng/ml with a C.V. of 16%.

PMID- 9140769
TI  - Analysis of tamoxifen-induced DNA adducts by 32P-postlabelling assay using
      different chromatographic techniques.
AB  - DNA isolated from livers of rats receiving tamoxifen was analysed by the 32P
      postlabelling method. The postlabelled DNA hydrolysis mixture was analysed both
      by reversed-phase HPLC with 32P on-line detection and by TLC on polyethyleneimine
      plates followed by autoradiography. Using the HPLC method, five well separated
      adduct peaks could be detected, while by the TLC method, two groups of adduct
      spots were observed. The detection limit of the TLC assay was lower (0.5
      adducts/10(10) nucleotides) than that of the HPLC assay (3 adducts/10(10)
      nucleotides). Thus, the TLC assay is more sensitive but also more laborious. The
      advantages of the HPLC assay were, in addition to better resolution, the ease of
      quantification and operation.

PMID- 9140771
TI  - Derivatization and high-performance liquid chromatographic analysis of
      pentaazapentacosane pentahydrochloride.
AB  - A rapid high-performance liquid chromatographic method for determination of the
      dansyl derivative of pentaazapen-tacosane (PAPC) pentahydrochloride has been
      developed. The chromatographic system uses a reversed-phase C8 column, a mobile
      phase of acetic acid buffer and acetonitrile and UV detection. The dansylation
      conditions were optimized with a pH of 11.0 and a 20-fold dansyl chloride excess.
      The yield of dansyl PAPC increased 10-fold as the reaction pH was changed from
      9.5 to 10.5. Under derivatization conditions of pH 8.5-11.0 and 1-30-fold excess
      dansyl chloride only perdansyl PAPC was found.

PMID- 9140770
TI  - Simple and versatile high-performance liquid chromatographic method for the
      simultaneous quantitation of the lactone and carboxylate forms of camptothecin
      anticancer drugs.
AB  - The well documented hydrolysis of the alpha-hydroxy-delta-lactone ring moiety in
      camptothecin and related analogues is routinely monitored using high-performance
      liquid chromatography (HPLC). Previous HPLC separations of the lactone and
      carboxylate forms of camptothecins have often required mobile phases containing
      three to four components; ion-pairing reagent to provide adequate retention of
      the carboxylate form of the drug; buffer to control the ionic strength and pH of
      the mobile phase; acetonitrile to control the retention of the lactone form and,
      in some instances, sodium dodecyl sulfate to reduce peak tailing. Because of the
      complexity of the mobile phases employed, development of these assays can be a
      laborious process, requiring re-optimization for each new analogue. In this
      study, we have developed a simple HPLC methodology for the simultaneous
      separation of the lactone and carboxylate forms of numerous camptothecin
      analogues. The mobile phase employed includes only triethylamine acetate (TEAA)
      buffer and acetonitrile. In this application, triethylamine serves multiple
      roles; as the ion-pairing reagent, as a masking agent for underivatized silanols
      and as the major buffer component. By altering only the composition of TEAA
      buffer with respect to acetonitrile, method development becomes a more
      streamlined and time efficient process. In this publication, we present the
      simultaneous separation of the lactone and carboxylate forms of camptothecin and
      four related analogues, namely, topotecan, GI147211, 10-aminocamptothecin and the
      CPT-11-SN-38 drug-metabolite pair. It is proposed that this new mobile phase,
      consisting of only triethylamine acetate buffer and acetonitrile, can be used for
      the analysis of the several camptothecin derivatives presently in clinical trials
      as well as the numerous other analogues in preclinical development.

PMID- 9140772
TI  - Simultaneous determination of a novel anticancer drug, TAS-103, and its N
      demethylated metabolite in monkey plasma by high-performance liquid
      chromatography using solid-phase extraction.
AB  - A simple and rapid method for the analysis of a novel anticancer drug, TAS-103,
      and its metabolite demethyl-TAS-103 in monkey plasma has been developed. This
      method is based on high-performance liquid chromatography with visible detection
      at 460 nm after solid-phase extraction with a Sep-Pak Vac PS-2 cartridge. The
      extraction recoveries of each compound, including the internal standard TAS-1
      1018, were from 88 to 102%. The quantitation limit of each compound was 5.0 ng/ml
      in 0.5 ml of plasma. The coefficients of variation for each compound ranged from
      0.9 to 4.9%, and relative errors for each compound ranged from -3.8 to 4.6%. Both
      compounds in monkey plasma were stable at -80 degrees C for 39 days and the
      extracts were stable at ambient temperature for 24 h. This method has been
      demonstrated to be useful for the pharmacokinetic study of TAS-103 in monkey
      plasma after intravenous administration.

PMID- 9140773
TI  - Evaluation and separation of steroid-bovine serum albumin conjugates by high
      performance liquid chromatography.
AB  - The conventional methods for characterization of steroid immunogens are based on
      the determination of the total amount of hapten bound to the protein carrier
      either by the UV spectroscopy or titration of unsubstituted amino groups. These
      methods do not allow more detailed insight into the immunogen composition. HPLC
      of the immunogen combined with UV detection is a relatively rapid and convenient
      method enabling determination of the hapten content in each fraction and,
      eventually, separation of individual fractions differing in the hapten content or
      purification of crude product.

PMID- 9140774
TI  - Reduction of wall adsorption in capillary zone electrophoresis of a basic single
      chain antibody fragment by a cationic polymeric buffer additive.
AB  - Reduction of adsorptive protein-wall interactions by poly(diallyldimethyl
      ammonium chloride), a permanently cationic polymer, at a concentration of 0.5%
      (w/v) is demonstrated for a basic single-chain antibody fragment (scFv, pI about
      9.5) even in the range of physiological pH of around 7. The polymer additive
      forms a positively charged layer at the silica surface which reverses
      electroosmosis and leads to electrostatic repulsion of the positively charged
      basic protein.

PMID- 9140776
TI  - Sensitive determination of sulpiride in human plasma by high-performance liquid
      chromatography.
AB  - We developed a simple, sensitive and reliable method for the determination of
      sulpiride, a specific antipsychotic drug, in human plasma using high-performance
      liquid chromatography. A structurally related benzamide, tiapride, was used as
      the internal standard. A Sep-Pak C18 cartridge was used to extract a sample from
      1 ml of plasma. The extract was dissolved in methylene chloride, and then back
      extracted with 0.01 M hydrochloric acid. The aqueous layer was put on a
      octadecylsilica column with a mobile phase of 50% acetonitrile in 0.01 M
      phosphate buffer (pH 3.0). A fluorescence detector with excitation at 300 nm and
      emission at 365 nm was used for detection. The calibration curve was linear in
      the concentration range of 10-1500 ng/ml, and the lower limit of detection was 1
      ng/ml. We used this method to examine plasma levels of sulpiride in 14 inpatients
      being treated with sulpiride for 6 months. The determined plasma levels were 70.1
      1121.2 ng/ml, and the correlation between daily dose and plasma concentration was
      positive. This simple, reliable method is expected to be put to good use in
      forensic and hospital laboratories.

PMID- 9140775
TI  - Determination of isatin in urine and plasma by high-performance liquid
      chromatography.
AB  - A method for the detection and determination of isatin (indole-2,3-dione) in
      urine and plasma by high-performance liquid chromatography has been developed. It
      consists of a two-step purification using two different columns with UV
      detection. With this method, we have reconfirmed that isatin is present in human
      urine. We have also demonstrated that isatin is present in human plasma and that
      the isatin levels in spot urine samples reflect the plasma isatin levels. In the
      present report we describe a rapid and sensitive means of determining urine and
      plasma isatin for laboratories equipped with a high-performance liquid
      chromatography system.

PMID- 9140778
TI  - High-performance liquid chromatographic determination of the enantiomers of the
      benzoquinolinone LY191704, a human type 1 5 alpha-reductase inhibitor, in plasma.
AB  - A stereoselective reversed-phase liquid chromatographic method for the
      determination of compounds LY300502 and LY300503 (enantiomers of LY191704) in rat
      and dog plasma was developed. The assay involved extraction of the compounds
      using a strong cation-exchange solid-phase extraction column, from which the
      compounds are eluted with 1% of 1 M HCI in methanol. The enantiomers were
      separated on a Daicel Chiralcel OD-R column. The mobile phase consisted of water
      acetonitrile-methanol (50:40:10, v/v) at a flow-rate of 0.3 ml/min. UV detection
      was achieved at 220 nm. The disposition of the enantiomers of LY191704 in rats
      and dogs was found to be stereoselective and species specific.

PMID- 9140777
TI  - Rapid and selective analysis of secnidazole in human plasma using high
      performance liquid chromatography with ultraviolet detection.
AB  - A rapid, reproducible high-performance liquid chromatographic method for the
      determination of secnidazole, 5-nitroimidazole class of antiprotozoals from blood
      is described. Metronidazole was used as an internal standard. A simple extraction
      step with dichloromethane was done before chromatography on a C18 column with the
      wavelength fixed at 276 nm on the UV detector. Blood levels up to 500 ng/ml have
      been measured with good precision in the healthy volunteers after 1 g of
      secnidazole was administered. The present described method can readily be
      utilized for routine pharmacokinetic studies.

PMID- 9140779
TI  - Enantioselective determination of S-(+)- and R-(-)-ondansetron in human serum
      using derivatized cyclodextrin-modified capillary electrophoresis and solid-phase
      extraction.
AB  - A high-performance capillary electrophoresis (HPCE) assay method for the
      quantitation of S-(+)- and R-(-)-ondansetron in human serum was developed.
      Resolution was achieved using 15 mM heptakis-(2, 6-di-O-methyl)-beta-cyclodextrin
      (DM-beta-CD) in 100 mM phosphate buffer (pH 2.5). A 72-cm untreated fused-silica
      capillary, at a constant voltage of 20 kV, was used for the analysis. A 0.03-mM
      cationic detergent was used as a buffer additive to decrease the adsorption of
      endogenous substances onto the silica wall. The analytes of interest were
      isolated from endogenous substances using a solid-phase extraction procedure. The
      cyanopropyl cartridge gave good recoveries in excess of 85% for both S-(+)- and R
      (-)-ondansetron, without any interferences. To decrease the limits of detection
      of the analytes, an on-capillary sample concentration technique was employed. The
      detection limit was 10 ng/ml using 2 ml of serum and the limit of quantitation
      was 15 ng/ml. The calibration curve was linear over a range of 15-250 ng/ml, with
      procainamide as the internal standard, and the coefficients of determination
      obtained were greater than 0.999 (n = 3). Precision and accuracy of the method
      were 2.76-5.80 and 2.10-5.00%, respectively, for S-(+)-ondansetron, and 3.10-6.57
      and 2.50-4.35%, respectively, for R-(-)-ondansetron. The HPCE method is a useful
      alternative to existing chiral high-performance liquid chromatographic methods.

PMID- 9140780
TI  - Interference of a methotrexate derivative with urinary oncopterin [N2-(3
      aminopropyl)biopterin] measurement by high-performance liquid chromatography with
      fluorimetric detection.
AB  - We previously reported a HPLC assay method using fluorimetric detection for the
      simultaneous determination of urinary N2-(3-aminopropyl)biopterin (oncopterin, a
      natural pteridine newly found in urine from cancer patients), biopterin and
      neopterin. We now have observed that an unknown substance, which may be derived
      from methotrexate, in urine from a patient with stomach cancer interfered with
      the assay of oncopterin and demonstrated that oncopterin could be completely
      separated from the unidentified substance by HPLC using a Nucleosil 100-5SA
      strong cation-exchange column. Furthermore, oncopterin was not detectable by this
      HPLC-fluorimetric method in urine samples from patients with stomach cancer who
      were not treated with methotrexate. The content of urinary oncopterin from cancer
      patients is supposed to be very low, with less than 1 mumol/mol creatinine. The
      present results indicate that the peak found with elution from the C18 column was
      a methotrexate-derived compound and co-eluted with the analyte oncopterin.

PMID- 9140781
TI  - Blood pressure reactions to the cold pressor test and the prediction of future
      blood pressure status: data from the Caerphilly study.
AB  - The prognostic significance of the cold pressor test in hypertension remains a
      matter of controversy. Following determination at an initial screening session,
      blood pressure (BP) was recorded at baseline rest and in reaction to a cold
      pressor test. Follow-up screening BP was determined 5 years later. The effective
      sample was 1039 men, with an average age of 56.6 years at initial screening. Step
      wise multiple regression indicated that BP reactions to the cold pressor test
      provided minimal independent prediction of follow-up BP over and above that
      afforded by BP at initial screening. In the case of follow-up systolic pressure,
      a model including only age and initial screening systolic BP (SBP) accounted for
      38% of the variance; SBP reactions to the cold pressor did not enter the
      regression equation. In the case of follow-up diastolic BP (DBP), diastolic
      pressure at initial screening accounted for 21% of the variance, and while DBP
      reaction to the cold pressor test entered the equation, it accounted for only an
      additional 1% of the variance. These results suggest that the cold pressor test
      may be of limited clinical use in older populations.

PMID- 9140782
TI  - Cardiovascular response to physical stress in offspring of hypertensive parents:
      Dutch Hypertension and Offspring Study.
AB  - Blood pressure (BP) regulatory mechanisms were studied in youngsters with
      contrasting risks for hypertension, based on parental history, during physical
      stress. As a static exercise, an isometric handgrip task (22% of maximal force
      during 5 min) was used and a dynamic exercise task was performed on a bicycle
      ergometer. At rest and during stress, BP and heart rate were recorded. In order
      to study the adaptation of the cardiovascular system to physical stress, cardiac
      output and total peripheral resistance were measured in addition to indices of
      vagal and sympathetic influences on the heart. Heart rate and cardiac output
      declined significantly more in offspring of hypertensive parents during static
      exercise (difference in heart rate: -2.5 +/- 1.2 bpm, P = 0.04; difference in
      cardiac output: -9.0 +/- 4.6%, P = 0.05). This is most likely the result of a
      larger increase in the total peripheral resistance in youngsters at risk
      (difference: 13.2 +/- 6.8%, P = 0.06). No differences between the two groups were
      found in reactivity of BP or in the indices of sympathetic activation or vagal
      inhibition of the heart. The offspring of hypertensive parents showed an
      attenuated increase in stroke volume during the dynamic exercise task (difference
      at the first cycling level: -11.5 +/- 5.4%, P = 0.04), while no difference in
      neural activity or heart rate was found. Youngsters with a parental history of
      hypertension show an enhanced reactivity of total peripheral resistance during
      static exercise. This does not lead to a higher BP response in this group, most
      probably because of a larger decrease of the cardiac output. During dynamic
      exercise the physiological increase in stroke volume is blunted in offspring of
      hypertensive parents.

PMID- 9140783
TI  - Effects of antihypertensive therapy on left atrial function.
AB  - OBJECTIVES: To investigate left atrial (LA) function as a reservoir, as a conduit
      and as a booster pump in essential hypertension (EH). LA volumes were
      echocardiographically measured in 28 untreated hypertensive patients and in 20
      control subjects. BACKGROUND: LA makes a large contribution in left ventricular
      filling, especially in patients with impaired diastolic function. LA function is
      fundamental in left ventricular filling in hypertensive patients as hypertension
      results in left ventricular diastolic dysfunction. METHODS: Diagnosis of EH
      (blood pressure > 140/90 mm Hg) was based on three repeated readings of blood
      pressure (BP). Patients with myocardial infarction, cardiomyopathy, valvular or
      congenital heart disease were excluded. Doppler diastolic early (E) and late (A)
      velocity of mitral inflow were measured. The following indexes were calculated:
      left ventricular mass index (LVMI) using the Penn convention; left ventricular
      stroke volume (LVSV); LA reservoir volume (LARV = LA maximal volume at mitral
      valve opening minus minimal volume); LA conduit volume (LACV = LVSV-LARV). Atrial
      systolic function was assessed by calculating the active emptying fraction
      (volume at onset of atrial systole minus minimal volume/volume at onset of atrial
      systole, the E/A ratio and the LA ejection force (0.5 rho A2 MOA, where rho = the
      density of blood, MOA = mitral orifice area from the parasternal short axis
      view). Measurements were obtained in all hypertensive patients before and after
      16 weeks administration of either enalapril (10 or 20 mg) or enalapril +/-
      chlorthalidone (20/25 mg) once a day. RESULTS: After 16 weeks of treatment, BP
      was reduced significantly (from 172/110 to 137/86 mm Hg, P < 0.001). LVMI
      decreased significantly as well (from 141 to 123 g/m2) although it was higher
      compared to controls (94 g/m2, P < 0.001). LARV decreased significantly (from
      35.4 to 29.3 cm3, P < 0.05) while LACV increased significantly (from 43.8 to 51.3
      cm3, P < 0.05), LA active emptying fraction and E/A ratio did not change. LA
      ejection force decreased significantly (from 20.9 to 18.1 kdynes, P < 0.05) but
      it was greater than controls (16.7 kdynes, P < 0.01). There was a positive
      relationship of LVMI to LARV (P < 0.01) in controls (r = 0.77) which held true in
      hypertensive patients, before (r = 0.72) and after treatment (r = 0.69). There
      was a negative relationship of LVMI to LACV (P < 0.01) in controls (r = -0.65),
      and in hypertensive patients untreated (r = -0.74) and after treatment (r = 
      0.72). CONCLUSIONS: Our results showed that in hypertensive patients, LA
      reservoir function increases and LA conduit function decreases, while LA ejection
      force increases. Antihypertensive treatment with enalapril and/or thiazide,
      induces normalisation of the LA function in parallel to left ventricular
      hypertrophy regression.

PMID- 9140784
TI  - Increased left ventricular mass in salt-sensitive hypertensive patients.
AB  - Clinical, biochemical and echocardiographic characteristics were evaluated from
      50 essential hypertensive patients classified asccording to their salt
      sensitivity status. Salt-sensitive hypertension was diagnosed by means of
      ambulatory blood pressure monitoring (ABPM) in 22 (44%) patients showing a
      significant increase in mean BP (P < 0.05) from a 7-day period of low salt (20
      mmol NaCl/day) intake, to a 7-day period of high salt (260 mmol NaCl/day) intake.
      The remaining 28 (56%) patients were considered as having salt-resistant
      hypertension. Compared with salt-resistant patients, salt-sensitive ones showed
      an increased left ventricular mass index (P = 0.0118), septal (P = 0.0021) and
      posterior wall thickness (P = 0.0026), without differences in the internal
      diastolic diameter. Decreased values of HDL-cholesterol (P = 0.0475) and
      increased total cholesterol/HDL-cholesterol ratio (P = 0.0098) were also observed
      in the salt-sensitive, compared with the salt-resistant hypertensive patients.
      Age, gender, body mass index, systolic and diastolic BP, fasting plasma glucose,
      creatinine and uric acid did not differ between salt-sensitive and salt-resistant
      patients. We conclude that, at the same level of BP, salt-sensitive patients
      exhibit an increased prevalence of left ventricular hypertrophy and a worse lipid
      profile. These two aspects may confer to salt-sensitive patients an increased
      risk in terms of cardiovascular morbidity and mortality.

PMID- 9140785
TI  - How common is heart failure due to systemic hypertension alone in hospitalised
      Nigerians?
AB  - Hypertension is regarded as the most common cause of heart failure in Nigeria and
      other Black African countries. A few reports suggest that heart failure due to
      hypertension hardly occurs without the presence of an extra burden on the heart
      from the presence of other cardiac risk factors. This study assesses the
      occurrence of other potential causes of heart failure in 55 consecutive admitted
      cases of hypertensive heart failure. All but six cases (88%) were associated with
      the presence of one or other significant cardiac risk factors while 56.2% were
      associated with multiple heart failure risk factors. Five of the six were poor
      drug compliers. Of the six, only one was completely free of cardiac risk factors
      and he was unaware of his hypertension and so had never had therapy. The others
      either consumed alcohol moderately, had mild renal impairment or were grossly
      obese. The factors found were anaemia, renal dysfunction, abnormal glucose
      tolerance, alcoholic ingestion and co-existing valvular heart disease. The
      finding shows that among Nigerian patients hospitalised for hypertensive heart
      failure, heart failure was rare in those hypertensive patients who had no extra
      cardiac burden, and therefore control of these factors will help prevent the
      development of heart failure in hypertension with its dismal prognosis.

PMID- 9140786
TI  - Blood pressure measurement in the community: do guidelines help?
AB  - The measurement of blood pressure (BP) is a crucial part of clinical assessment
      and hypertension management, and is commonly performed inaccurately despite the
      publication of National and International consensus guidelines for its
      measurement. There have been no previous reports on the self-reported knowledge
      base of General Practitioners (GPs) and Practice Nurses (PNs) with regard to BP
      measurement. A postal questionnaire survey was conducted of 831 community-based
      practitioners (550 GPs and 281 PNs) in north west London. The overall response
      rate was 61%. Previous education in BP measurement was recorded in 87% of the GPs
      and 95% of the nurses. Precision factors were recorded for the GPs and nurses
      respectively including rounding up or down (GP 67%, PNs 48%), routine use of
      diastolic phase V (GP 63%, PNs 70%), reading the BP to the nearest 2 mm mercury
      (GP 54%, PNs 70%) and failure to use a large BP cuff in the past 4 weeks (GP 33%,
      PNs 26%). Only 12% of the GPs and 19% of the nurses were able to name the source
      of the published guidelines. Overall the nurses had a statistically significantly
      greater knowledge base than the GPs, and both community groups had a greater
      knowledge for core questions than hospital practitioners from two previous
      surveys. Knowledge of a guideline source was associated with improved self
      reported BP technique. There was a difference between reading and recording
      accuracy which deserves further study. These results show that there are
      important gaps in the knowledge of community practitioners with regard to the
      technique of BP measurement.

PMID- 9140787
TI  - Case report: moderate salt restriction for the management of hypertension and
      hypercalciuria.

PMID- 9140788
TI  - Prevalence and associated factors of hypertension: results from a three community
      based survey, Jordan.
AB  - The aim of this study was to estimate the prevalence of hypertension, to
      determine its association with certain cardiovascular disease risk factors, and
      to evaluate level of hypertension awareness and control in an adult population in
      Jordan. The study used a cross-sectional population survey of a systematic sample
      of three communities. Data for the sample of 2299 adults, aged 25 years and
      older, were collected from September 1994 to September 1995. A total of 370
      subjects or 16.1% were found to have hypertension. The prevalence rate was higher
      among women (17.1%) than men (14.4%). Logistic regression analysis indicated that
      hypertension was positively associated with gender, age, family history of
      hypertension, diabetes mellitus, and total serum cholesterol, but negatively
      associated with level of education. No association between hypertension and
      smoking was detected in this study. About one-half (48.6%) of hypertensives in
      this study were unaware of their diagnosis. Awareness of hypertension was
      positively associated with age and family history. More than one-third (36.5%) of
      those aware of their diagnosis did not achieve control of their hypertension.
      Hypertension appears to be a common public health problem in Jordan. Awareness
      and control of hypertension are far below optimal levels.

PMID- 9140789
TI  - Age- and gender-dependent association of the angiotensin-converting enzyme gene
      with essential hypertension in a Chinese population.
AB  - A case-control study was carried out on 272 Chinese subjects over 40 years of
      age, including 157 hypertensives and 115 normotensives, to examine the
      association between angiotensin-converting enzyme (ACE) gene insertion/deletion
      (I/D) polymorphism and blood pressure (BP) status. The I/D polymorphism of the
      ACE gene was identified by polymerase chain reaction. As a whole group, the
      difference of allele frequencies between normotensives and hypertensives was
      statistically significant (chi 2 = 4.46, P = 0.03; D/I odds = 1.46), while there
      was no difference in the genotype distribution (chi 2 = 3.95, P = 0.13). In a
      subgroup with elderly hypertension (age > 65), the frequencies of D-allele and DD
      genotype significantly increased (chi 2 = 4.43, P = 0.03 and chi 2 = 4.03, P =
      0.08, respectively; D/I odds = 2.28). The association and relative risk increased
      further in the male gender (chi 2 = 6.65, P = 0.01 and chi 2 = 7.51, P = 0.02
      respectively; D/I odds = 4.57 and DD/II odds = 12.00 respectively). The D-allele
      increased with age in the hypertensives, while the I-allele increased with age in
      normotensives. Thus, we conclude that the deletion polymorphism of the ACE gene
      is significantly associated with male elderly hypertension, at least in this
      Chinese population. This observation, if proved in a larger population, may have
      some implications for the prevention and treatment strategy for elderly
      hypertension.

PMID- 9140790
TI  - Insertion/deletion polymorphism of the angiotensin-converting enzyme gene and
      loss of the insertion allele in aldosterone-producing adenoma.
AB  - The genetic mechanisms responsible for the formation of adrenocortical adenomas
      which autonomously produce aldosterone are largely unknown. The adrenal renin
      angiotensin system has been implicated in the pathophysiology of these tumours.
      Angiotensin-converting enzyme (ACE) catalyses the generation of angiotensin II,
      and the insertion/deletion (I/D) polymorphism of the ACE gene regulates up to 50%
      of plasma and cellular ACE variability in humans. We therefore examined the
      genotypic and allelic frequency distributions of the ACE gene I/D polymorphism in
      55 patients with aldosterone-producing adenoma, APA, (angiotensin-unresponsive
      APA n = 28, angiotensin-responsive APA n = 27), and 80 control subjects with no
      family history of hypertension. We also compared the ACE gene I/D polymorphism
      allelic pattern in matched tumour and peripheral blood DNA in the 55 patients
      with APA. The frequency of the D allele was 0.518 and 0.512 and the I allele was
      0.482 and 0.488 in the APA and control subjects respectively. Genotypic and
      allelic frequency analysis found no significant differences between the groups.
      Examination of the matched tumour and peripheral blood DNA samples revealed the
      loss of the insertion allele in four of the 25 patients who were heterozygous for
      the ACE I/D genotype. The I/D polymorphism of the ACE gene does not appear to
      contribute to the biochemical and phenotypic characteristic of APA, however, the
      deletion of the insertion allele of the ACE gene I/D polymorphism in 16% of
      aldosterone-producing adenomas may represent the loss of a tumour suppressor
      gene/s or other genes on chromosome 17q which may contribute to tumorigenesis in
      APA.

PMID- 9140791
TI  - Antihypertensive efficacy and orthostatic tolerance of bunazosin vs nitrendipine:
      a multicentre double-blind randomized controlled study.
AB  - A multicentre double-blind randomized controlled study was conducted in 358
      patients with mild to moderate essential hypertension. The goal was to compare
      the antihypertensive efficacy, tolerability, and in particular postural
      hypotension of the alpha 1-adrenoreceptor blocker bunazosin with the calcium
      channel blocker nitrendipine. Both treatment groups had comparable baseline blood
      pressure (BP) values, namely diastolic BP (DBP) of 103.8 +/- 5.6 mm Hg in the
      bunazosin group, and 103.4 +/- 6.0 mm Hg in the nitrendipine group, respectively.
      Baseline systolic BPs (SBP) were 149.7 +/- 14.4 mm Hg (bunazosin) and 149.2 +/-
      14.3 mm Hg (nitrendipine). After 12 weeks of therapy, reduction of DBP (-6.1 +/-
      11.7 mm Hg on bunazosin vs -6.9 +/- 9.9 mm Hg on nitrendipine; P = n.s.), and SBP
      (-4.4 +/- 14.3 mm Hg on bunazosin vs -7.0 +/- 14.4 mm Hg on nitrendipine; P =
      n.s.) was similar in both groups. During a provocative orthostatic tolerance test
      after the first dose, the incidence of prae-collapses (ie termination of the test
      due to orthostatic complaints) was higher on bunazosin (17 vs 2; P < 0.05) but
      orthostatic dysregulation symptoms (symptom score 1.37 on bunazosin vs 0.95 on
      nitrendipine; n.s.) and collapses (four on bunazosin vs one on nitrendipine;
      n.s.) occurred to a similar extent in both treatment groups. Three and 9 weeks
      after treatment, no increased susceptibility to orthostatic stress compared to
      baseline could be found in either group. Under daily life conditions, the
      frequency of orthostatic dysregulation was identical in both groups (0.8%).
      Bunazosin, however, was far better tolerated with 43.8% of the patients
      complaining of adverse events as opposed to 63.6% on nitrendipine (P < 0.001).
      The rate of early discontinuations due to adverse events was only 1.3% on
      bunazosin compared to 13.6% on nitrendipine (P < 0.001). In conclusion, bunazosin
      has a similar antihypertensive efficacy as nitrendipine. Despite an initially
      higher susceptibility to orthostatic stress under a provocative manoeuver,
      bunazosin evoked the same low incidence of orthostatic dysregulation symptoms as
      nitrendipine under daily life conditions, but was significantly better tolerated
      than nitrendipine.

PMID- 9140792
TI  - A multicenter, parallel comparative study of the antihypertensive efficacy of
      once-daily lisinopril vs enalapril with 24-h ambulatory blood pressure monitoring
      in essential hypertension.
AB  - The aim of the study was to compare the antihypertensive efficacy of once-daily
      lisinopril vs enalapril both during normal daily activity and sleep, in mild-to
      moderate essential hypertension. After a 4-week wash-out period, 34 patients (17
      M, 17 F) aged 22 to 67 years were randomized in a multicenter, open, parallel
      fashion: 17 received lisinopril (10-20 mg) and 17 enalapril (10-20 mg) for a 12
      week period. Twenty-four hour ambulatory blood pressure monitoring (ABPM) was
      performed using an oscillometric non-invasive automated device at both the end of
      the 4-week drug-free baseline period and during the last week of treatment. With
      no differences in initial blood pressure (BP) between groups, both drugs
      significantly reduced office and ABPM values. Lisinopril tended to reduce BP in a
      greater extension than enalapril, but only the reduction of office systolic BP
      (SBP) (p = 0.0062), 24-h SBP load (P = 0.0182) and night time SBP load (P =
      0.0316) reached statistical significance. We conclude that, in spite of a more
      prominent reduction of SBP by lisinopril, both drugs have a similar efficacy in
      reducing BP, assessed by both office and ABPM measurements.

PMID- 9140793
TI  - Commentary: has the random zero sphygmomanometer been exonerated?

PMID- 9140794
TI  - Mechanisms by which the Hawksley random zero sphygmomanometer underestimates
      blood pressure and produces a non-random distribution of RZ values.
AB  - Four faults are reported in the Hawksley Random Zero Sphygmomanometer (RZS). Our
      study is of their mechanism. (i) Compared with a mercury sphygmomanometer the RZS
      underestimates blood pressure (BP). We confirm this: for 240 measurements by
      three experienced operators in 12 patients, systolic BP was 3.4 mm Hg lower in
      the RZS; diastolic pressure was not underestimated. A cause of under-estimation
      in 89% of measurements was that mercury stuck in the manometer giving a false
      high reading of random zero (RZ). Tilting the RZS before reading RZ reduced under
      reading by 1.6 mm Hg. A rare cause is failure of the operator to completely close
      the reservoir tap. (ii) Values of RZ are not randomly distributed; non-randomness
      is most marked in measurements made by experienced operators whose speed of
      measurement provides insufficient time during cuff inflation for filling of the
      diaphragm chamber. Smaller contributions are made by the sticking of mercury in
      the manometer and by a leak of air through the air bleed screw. (iii) Consecutive
      RZ estimates often have similar value. This has two causes: short cuff inflation
      time and short interval between opening the reservoir tap and spinning the thumb
      wheel. (iv) An inverse relation of RZ and BP suggested by earlier work and by our
      own data is probably an artifact: when BP is low, measurement is quick and RZ is
      falsely high; when BP is high, measurement takes longer and RZ is lower. These
      four faults could be partly or wholly avoided by a change in the operators'
      technique.

PMID- 9140795
TI  - The natural history of borderline hypertension in a Chinese population.
AB  - One hundred and thirty-one borderline hypertensive patients were followed up for
      17 years. A cohort of normotensives strictly matched by age, sex, region and
      occupation served as controls (1:1). It was found that 64.6% of borderline
      hypertensive patients developed into established hypertensives after 17 years
      follow-up, 25.5% restored to normotensives and 13.8% remained unchanged. The
      total mortality rate of borderline hypertensives was higher than that of
      normotensives (27.9 vs 13.4/1000 person years), and the relative risk of total
      death in borderline hypertensives was 2.35. The main cause of death was stroke,
      accounting for 42.5% of the total death rate. The relative risk rates of
      occurrence and death associated with stroke were 8.3 and 11.6, respectively. It
      is concluded that the main complication of borderline hypertension was stroke
      rather than coronary heart disease, which was similar to that of established
      hypertension in this area. Part of the borderline hypertensives need to be
      treated to reduce the risk of cardiovascular complications.

PMID- 9140796
TI  - Pressure response to successive clinic readings predicts an elevated blood
      pressure at 2.6 years' follow-up: the Israeli CORDIS Study. Cardiovascular
      Occupational Risk Factor Determination in Israeli Industries.
AB  - BACKGROUND: Many persons exhibit an elevation in blood pressure (BP) when
      examined in a medical setting. We examined whether individuals exhibiting an
      exaggerated pressure response (high responders) to BP determination would have an
      elevated baseline BP on follow-up, independent of the initial BP level. METHODS
      AND RESULTS: A total of 1217 employed men not on hypertensive medication, aged 20
      64 years were examined over 2-4 years (mean 2.6 years) following the baseline
      measurements at entry. Pressure response was assessed at entry and defined as the
      difference between the first and fourth values in successive readings. Such a
      response was apparent for systolic BP (SBP) but was negligible for diastolic BP
      (DBP) and the former was negatively related to the baseline BP value. High
      responders were defined as persons showing a pressure response greater than the
      average for the respective subgroup with an initially similar baseline BP value.
      Logistic regression results indicated that those with high SBP responsivity had a
      2.7 times greater chance of having an elevated SBP (> or = 140 mm Hg) on follow
      up (95% CI 1.8-4.1, P < 0.001), independently of initial SBP, age, or body mass
      index. Other significant predictors were the initial baseline SBP value and age.
      In those with an initial SBP of 130-139 mm Hg, the baseline SBP was not
      predictive of future readings whereas high responders had a four times higher
      risk of having an elevated SBP on follow-up (OR = 4.0, 95% CI 2.0-8.0, P <
      0.001). CONCLUSIONS: These findings suggest that SBP hyperresponsivity, to BP
      determination at the clinic independently predicts elevated SBP 2.6 years later.
      Further studies are warranted to determine the predictive value over a longer
      follow-up period.

PMID- 9140797
TI  - ACE, angiotensinogen and obesity: a potential pathway leading to hypertension.
AB  - The renin-angiotensin system (RAS) plays a crucial role in the regulation of
      fluid volume, thereby influencing blood pressure (BP). Obesity is an important
      risk factor for hypertension, however the physiologic basis for this relationship
      has not been clarified. In a population survey we examined the potential
      relationship between the RAS and obesity. Based on community sampling, 449
      individuals were recruited from metropolitan Kingston, Jamaica. Serum angiotensin
      converting enzyme (ACE) and circulating angiotensinogen levels were measured and
      the associated genes were typed for previously described polymorphisms. Obese
      individuals (body mass index > 31) had significantly higher serum ACE and
      angiotensinogen levels, this relationship persisted for ACE in multivariate
      analyses controlling for BP, hypertension status, age, and gender. The
      insertion/deletion polymorphism of the ACE gene was associated with variation in
      the levels of ACE, but inconsistently with body mass index. Variants of the
      angiotensinogen gene leading to amino acid substitutions at positions 174 and 235
      did not influence levels either of angiotensinogen or obesity. These data suggest
      that obesity may alter the levels of ACE and angiotensinogen, and provide a
      potential pathway through which obesity leads to elevation of BP.

PMID- 9140798
TI  - The atrial natriuretic peptide gene and essential hypertension in African
      Caribbeans from St Vincent and the Grenadines.
AB  - Atrial natriuretic peptide (ANP) which alters sodium balance, blood volume and
      vascular tone represents an important candidate for investigating the genetic
      basis of essential hypertension (EH). Accordingly, we have studied Bgl1 and Xho1
      restriction fragment length polymorphisms (RFLPs) of the ANP gene in 147
      hypertensive, 141 normotensive and 67 population-based control subjects from a
      homogenous population of West African origin from St Vincent and the Grenadines.
      We found no association of either Bgl1 and Xho1 RFLPs with EH. This study
      suggests that the ANP locus may not exert a major gene effect on EH amongst the
      black people of St Vincent and the Grenadines.

PMID- 9140799
TI  - The influence of exercise on albumin excretion rate in borderline hypertensives
      and in offspring of hypertensive parents.
AB  - We investigated exercise induced urinary albumin excretion rate (UAE)(ex-UAE) in
      patients with borderline hypertension (BH) compared to normotensives with
      positive-PFH and negative-NFH family history of hypertension. The study
      population consisted of 20 young, non-obese males with BH defined according to
      WHO criteria and confirmed by 24 h ambulatory blood pressure (ABP) and 40 healthy
      matched normotensives (PFH = 20 and NFH = 20). Twenty-four hour UAE was assessed
      by day and night time urine collection. BH and normotensive subjects performed a
      20 min ergometric graded exercise test. The relationship between 24 h UAE, 24 h
      ABP and 2-D-echocardiographic left ventricular mass index (LVMI) were examined.
      The three groups did not differ in 24 h UAE. Exercise induced a significant
      increase in UAE only in BH. Exercise induced UAE was greater in BH compared to
      normotensives: BH = 54.3(21-125), PFH = 37.6(13-62), NFH = 9.7(0
      35)micrograms/min, data expressed as median (I quartile-III quartile). Pooled
      data from all three groups showed a positive correlation between ex-UAE and
      systolic BP (SBP) during night time (by multiple regression analysis). In
      conclusion, BH without other known cardiovascular risk factors, moderate dynamic
      exercise induced an excessive increase in UAE.

PMID- 9140800
TI  - Blood pressure during siesta: effect on 24-h ambulatory blood pressure profiles
      analysis.
AB  - Blood pressure (BP) during siesta declines to levels similar to those of night
      time sleep. The objective of the study was to assess the effect of siesta on 24-h
      ambulatory BP (ABP) data. Two different approaches were employed for the
      definition of day and night periods: (1) actual patient reported day and night
      intervals (ACT) with siesta period analysed as a third time period; and (2)
      arbitrary day and night time intervals (ARB) with the presence of siesta being
      ignored. A total of 203 24-h ABP recordings were analysed, with a siesta during
      ABP monitoring reported in 154 of them. Mean siesta BP was very close to ACT
      night time BP. Among recordings with a siesta, ACT daytime BP was higher and
      night time BP lower than the corresponding ARB BPs (P < 0.001). The magnitude of
      night time BP drop was greater with ACT intervals, resulting in a lower
      percentage of non-dippers (P < 0.001). Among 49 recordings without a siesta,
      differences between ACT and ARB BPs were less pronounced for daytime but not for
      night time. Differences in the magnitude of nocturnal BP drop between ACT and ARB
      periods, although statistically significant, did not affect the prevalence of non
      dippers. In conclusion, analysis of 24-h BP profiles by using ARB instead of ACT
      day and night intervals results in underestimation of the nocturnal BP drop and
      overestimation of the proportion of non-dippers. This bias is more pronounced in
      patients who take a siesta during ABP monitoring.

PMID- 9140801
TI  - Antihypertensive treatment with moexipril plus HCTZ vs metoprolol plus HCTZ in
      patients with mild-to-moderate hypertension.
AB  - Combination therapy with the new ACE inhibitor moexipril plus hydrochlorothiazide
      (HCTZ) results in significant blood pressure (BP) reductions. This study compares
      the efficacy and safety of moexipril plus HCTZ to that of a standard combination
      treatment in patients with mild-to-moderate hypertension. After a 1 month placebo
      run-in period, 140 hypertensive patients whose sitting diastolic BP (DBP)
      averaged 95-114 mm Hg were randomized to receive either once daily moexipril 7.5
      mg/HCTZ 12.5 mg or metoprolol 100 mg/HCTZ 12.5 mg for the following 12-week
      double-blind treatment period. At biweekly visits BP was controlled
      sphygmomanometrically and the occurrence of adverse events (AE) was documented.
      At study endpoint adjusted mean reductions in sitting systolic/diastolic BP seen
      with both combinations were -17.6 mm Hg/-12.8 mm Hg and -17.2 mm Hg/-13.9 mm Hg
      in the moexipril/HCTZ and metoprolol/HCTZ groups, respectively. The response rate
      to both kinds of combinations were very similar, 69% and 74% in the
      moexipril/HCTZ and metoprolol/HCTZ groups, respectively. The percentage of
      patients which experienced one or more AEs were 46% in the moexipril/HCTZ and 61%
      in the metoprolol/HCTZ group. Headache and cough which are the most frequently
      reported AEs after treatment with ACE inhibitors were seen in 9% and 10% of the
      patients in the moexipril/HCTZ group compared to 10% and 4% in the
      metoprolol/HCTZ group. The study indicates that the combination of moexipril 7.5
      mg plus HCTZ 12.5 mg is as efficacious and safe as metoprolol 100 mg plus HCTZ
      12.5 mg in the treatment of mild-to-moderate hypertension.

PMID- 9140802
TI  - A dose-response trial of nebivolol in essential hypertension.
AB  - A double-blind placebo-controlled dose-response trial of nebivolol, a
      cardioselective beta-blocking drug which also induces endothelium-dependent
      dilatation via nitric oxide, has been performed. Nebivolol reduced blood pressure
      (BP) in a dose dependent way, and was shown to be effective given once daily,
      without appreciable differences between peak and trough drug levels. There was no
      postural component to the BP fall. There was no clear inferiority of efficacy in
      black patients. A single daily dose of 5 mg was appropriate, with no evident
      advantage at 10 mg. The drug was well tolerated, even at 10 mg daily. BP control
      was achieved largely in the absence of typical side effects of beta-blockade. The
      combination of properties of nebivolol renders it an attractive addition to the
      antihypertensive repertoire.

PMID- 9140803
TI  - Ouabain-induced hypertrophy in cultured cardiac myocytes is accompanied by
      changes in expression of several late response genes.
AB  - Partial inhibition of cardiac Na/K-ATPase by digitalis drugs such as ouabain is
      the initial event leading to positive inotropy in the heart. We showed recently
      that exposure of rat cardiac myocytes to ouabain concentrations that produce
      positive inotropy, but no overt toxicity, caused inductions of some early
      response genes and hypertrophy of these myocytes. The aim of this work was to
      determine if ouabain also affects the expressions of certain late response genes
      that are regulated by other hypertrophic stimuli. Non-toxic concentrations of
      ouabain (5-100 microM) increased mRNAs of skeletal alpha-actin, atrial
      natriuretic factor, myosin light chain 2, and transforming growth factor beta:
      indicating that ouabain's effects on these marker genes are similar to those of
      hypertrophic stimuli that mimic the effects of pressure overload. Expression of
      skeletal alpha-actin was more sensitive to ouabain than that of atrial
      natriuretic factor, suggesting significant differences in the ouabain-specific
      pathways of the induction of these fetal genes. The effects of ouabain on
      skeletal alpha-actin gene were transcriptional, and required an increase in net
      influx of extracellular Ca2+. Protein kinase C and Ca(2+)-calmodulin kinases, but
      not protein kinase A, were involved in the signal pathways leading to the
      induction of skeletal alpha-actin gene. These data and our prior findings
      indicate that an increase in net influx of Ca2+ through partial inhibition of
      Na/K-ATPase initiates protein kinase-dependent pathways resulting in alterations
      in cardiac growth and expressions of both early and late response genes.

PMID- 9140804
TI  - The role of Gi-proteins and beta-adrenoceptors in the age-related decline of
      contraction in guinea-pig ventricular myocytes.
AB  - A decline in contractility in myocytes from ageing guinea-pig hearts was
      demonstrated, which is more pronounced for maximum beta-adrenoceptor-stimulated
      activity than contraction in high Ca2+. In this study the role of the inhibitory
      G-proteins (Gi) in this process was investigated. Comparisons were made between
      young (Y, < 400 g, < 4 weeks), adult (A. > 600 g, > 8 weeks) and senescent guinea
      pigs (S, 58-65 weeks, 1136 +/- 30 g). Gi alpha activity, detected by pertussis
      toxin-catalysed ADP ribosylation, was significantly increased in senescent
      compared to young animals, but immunodetectable levels of Gi alpha were
      unchanged, beta-adrenoceptor number was decreased by 27% in senescent compared
      with young animals (P < 0.002). Pertussis toxin treatment increased the maximum
      response to isoproterenol in contacting myocytes so that there was no longer any
      significant decline with age. Maximum contraction amplitudes (sarcomere length
      change, micron) with isoproterenol before pertussis toxin were 0.144 +/- 0.011
      (Y, n = 22 animals), 0.104 +/- 0.009 (A. 18) and 0.098 +/- 0.009 (S. 14), P <
      0.01 by analysis of variance (ANOVA). Following toxin treatment amplitudes were
      0.140 +/- 0.012 (Y. 12), 0.117 +/- 0.010 (A. 10) and 0.117 +/- 0.018 (S. 8), P =
      N.S. Pertussis toxin treatment also reversed the effects of ageing on contraction
      and relaxation velocity in isoproterenol. In contrast, the effect of age on
      contraction amplitude or velocity in maximum Ca2+ was more pronounced after toxin
      treatment. The EC50 value for isoproterenol increased with age: pertussis
      treatment decreased the EC50 in each group, but the effect was especially
      pronounced for senescent animals. There was no significant difference in the
      concentration-response curves for the negative inotropic effect of adenosine (in
      the presence of isoprotenerol) between the three age groups before toxin
      treatment. All effects of adenosine were abolished after pertussis exposure. We
      conclude that increased Gi alpha activity is likely to contribute to the
      decreased response to isoproterenol, but not to high Ca2+, in myocytes from
      ageing guinea-pigs.

PMID- 9140805
TI  - Inositol phosphate metabolism during myocardial ischemia.
AB  - Inositol phosphate release in intact heart in response to norepinephrine involves
      primarily release of inositol(1,4)bisphosphate (Ins(1,4)P2) rather than
      inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) but Ins(1,4,5)P3 release predominates
      under conditions of post-ischemic reperfusion. In the current study, effects of
      myocardial ischemia on inositol phosphate responses were examined. Global
      myocardial ischemia in rat ventricle caused a reduction in the content of
      [3H]Ins(1,4)P3 (70-90%) and [3H]Ins(1,4,5)P3 (46%) and altered the pattern of
      norepinephrine stimulation such that increases in [3H]Ins(1,4,5)P3 were observed.
      Simulated ischemia in isolated right atria or isolated ventricular myocytes (P
      alpha 2 16-20 mmHg. pH 6.7. KCl 10 mM) produced similar changes. Reduction in O2
      in the absence of other changes reduced the content of [3H]Ins (1,4)P2 (79%) in
      right atria whereas hypoxia and reduced pH were required to alter the
      [3H]Ins(1,4,5)P3 response. Progressive reduction in atrial ATP content using
      metabolic inhibitors caused a parallel decrease in [3H]Ins(1,4,5)P3 content (r =
      0.96) without affecting [3H]Ins(1,4)P2 or the isomers of InsP1, showing that
      levels of Ins(1,4)P2 and Ins(1,4,5)P3 are regulated differently in the heart.
      These findings show that effects of ischemia on inositol phosphates in heart are
      complex and multifactorial, with Ins(1,4)P2 being affected under more moderately
      ischemic conditions than required for alterations in Ins(1,4,5)P3. These studies
      also demonstrate that ischemia produces similar effects on the release and
      metabolism of inositol phosphates in heart regardless of the ischemic model or
      the myocardial preparation used.

PMID- 9140806
TI  - Progression of left ventricular hypertrophy does not change the sarcoplasmic
      reticulum calcium store in the spontaneously hypertensive rat heart.
AB  - The spontaneously hypertensive rat (SHR) is characterized by elevated blood
      pressure and the development of left ventricular hypertrophy. During compensatory
      hypertrophy in the SHR, (26 weeks) when baseline contractile function is normal
      or increased, the inotropic response to beta-adrenergic stimulation is impaired.
      We recently showed by electron probe microanalysis (EPMA) that the amount of Ca2+
      stored in the sarcoplasmic reticulum (SR) following sympathetic stimulation is
      not decreased in the 26-week-old SHR heart. However, with disease progression,
      cardiac function declines further in the SHR and the response to beta-adrenergic
      stimulation is more impaired. To determine whether a decreased availability of SR
      Ca2+ is responsible for the severely depressed inotropic response in the older
      SHR, we used EPMA to measure directly the amount of Ca2+ stored in the SR
      following activation of the beta-adrenergic pathway in papillary muscles from 76
      week-old SHR and Wistar-Kyoto (WKY) controls. In order to determine if there are
      other alterations in ion homeostasis, we also compared elemental content of A
      band and mitochondria. Papillary muscles from 76-week-old SHR and WKY were
      stimulated by 10 microM isoproterenol and then rapidly frozen during relaxation.
      The elemental content of the junctional SR. A-band and mitochondria was measured
      by EPMA. We observed no significant difference in SR Ca2+ content between SHR and
      WKY. There was also no strain-dependent difference in mitochondrial or A-band
      Ca2+. Overall, these results indicate that the impaired response to beta
      adrenergic stimulation in the SHR at 76 weeks is not due to altered availability
      of SR Ca2+.

PMID- 9140807
TI  - 1H NMR measurement of triacylglycerol accumulation in the post-ischemic canine
      heart after transient increase of plasma lipids.
AB  - This study tests the hypothesis that increased levels of plasma lipids can
      accelerate accumulation of myocardial triacylglycerols in post-ischemic but
      viable myocardium. Two groups of dogs underwent 90 min of left anterior
      descending coronary artery (LAD) occlusion followed by 240 min of reperfusion.
      The first group of saline-treated dogs (n = 7) had physiological levels of plasma
      lipids during reperfusion: a second group treated with Liposyn and heparin (n =
      5) experienced increased plasma lipids during reperfusion. The transmural content
      of triacylglycerols was determined during ischemia and reperfusion using 1H NMR
      one-dimensional chemical shift imaging (1D CSI), and at the end of reperfusion
      using Oil Red-O staining and chemical assay. TTC staining was used to identify
      the extent of irreversibly injured myocardium. Subepicardial and plasma
      triacylglycerol content, measured both by 1D CSI and chemically, did not change
      during reperfusion in saline-treated dogs. Infusing dogs with Liposyn and heparin
      for 90 min during reperfusion transiently elevated their plasma triacylglycerols,
      which returned to normal levels following Liposyn wash-out. During Liposyn wash
      out, myocardial triacylglycerols measured by 1D CSI preferentially increased in
      the subepicardium of area-at-risk myocardium (P < 0.05). Triacylglycerol content,
      measured chemically, also increased in area-at-risk compared to non-ischemic
      subepicardium (P < 0.001). Significant endocardial damage occurred in both
      groups, but elevated levels of plasma lipids did not increase the size of the
      area-at-risk. Therefore, elevated plasma lipids caused a preferential
      accumulation of triacylglycerols in area-at-risk myocardium during reperfusion
      without exacerbating irreversible ischemic injury. These results are consistent
      with either inhibited fatty acid oxidation or mis-matched fatty acid extraction
      and oxidation in area-at-risk myocardium.

PMID- 9140808
TI  - Proton inhibition of transient outward potassium current in rat ventricular
      myocytes.
AB  - Acidosis elicited during myocardial ischemia is a significant pathophysiological
      condition markedly affecting the electrical and contractile properties of heart
      muscle. We examined the effects of protons on K channel activity in rat
      ventricular myocytes by recording transient outward (Ito) and inward rectifier
      (IKl) K+ currents using the whole cell, voltage clamp technique. Proton
      concentration was controlled by independently varying the pH of HEPES-buffered
      external (pHo) or pipette (pHp) solutions. Mean Ito density in myocytes
      preconditioned in acidic external solution (pHo 6.0) for 15-20 min was
      significantly less than control cells equilibrated at physiological pHo. In
      contrast, IKl was not changed during this period of acidosis. External
      acidification did not decrease Ito when initiated after intracellular dialysis
      with standard pHp 7.2. However, when myocytes were dialyzed with acidic pHp, Ito
      density was significantly less than control, while alkaline pHp had little
      effect. Despite marked reduction in current density produced by low pHp
      solutions, steady-state activation and inactivation parameters of Ito were not
      significantly altered. In addition, the reversal potential of this current,
      kinetics of inactivation, and recovery from inactivation were not significantly
      affected by acidic or alkaline pHp solutions. Acidic pHp alone did not change IKl
      density compared with control, but when combined with Na+/H+ exchange blockade
      with 5-(N,N-dimethyl)-amiloride or Na(+)-free external solution, IKl density was
      significantly reduced. Our data suggest that protons inhibit Ito predominantly
      from the intracellular side of the channel, possibly by altering its conductance
      or gating properties. Moreover, intracellular protons differentially affect Ito
      and IKl channels, with the former exhibiting greater sensitivity for a given
      level of acidosis.

PMID- 9140809
TI  - Characterization of cytokine and iNOS mRNA expression in situ during the course
      of experimental autoimmune myocarditis in rats.
AB  - Ribonuclease protection assay was used to demonstrate mRNA expression of several
      cytokines as well as inducible NO synthase (iNOS), constitutive endothelial NO
      synthase (cNOS) and perforin in the myocardium during the course of experimental
      autoimmune myocarditis (EAM) in rats. Interleukin 2 (IL-2) appeared in the
      initial inflammatory phase (day 14), subsided in the maximum inflammatory phase
      (day 19) and disappeared by the recovery phase (day 25). mRNA of IL-3 beta,
      interferon gamma INF-gamma and tumor necrosis factor alpha (TNF-alpha) were
      detected only in the maximum inflammatory phase and iNOS also appeared for
      several days at this time. In contrast. IL-10 mRNA was detected after the maximum
      inflammatory stage and persisted into the recovery phase (days 25-36). Although
      transforming growth factor beta 1 (TGF-beta 1) could be detected in all phases,
      the expression was markedly enhanced in the maximum inflammatory phase and
      gradually diminished (around day 36) to basal levels. Perforin mRNA was not
      detected at any point in the disease. Besides macrophages and CD4 T cells, a
      number of neutrophils were found in the myocardium especially at peak
      inflammatory stage. We suggest that antigen (Ag) primed Ag presenting cells or
      macrophages interact with T cells (Th1) to produce IL-2 and subsequent IFN-gamma,
      which further activates macrophages in the myocardium. Consequently, TNF-alpha
      and iNOS may inflict tissue damage to myocardium. It is also suggested that TGF
      beta) and one representative Th2 cytokine, IL-10, help inhibit inflammation.
      These findings suggest that Th1 and Th2 cytokines are produced at different
      stages of EAM and modulate the inflammation and the course of EAM.

PMID- 9140811
TI  - A novel A/T-rich element mediates ANF gene expression during cardiac myocyte
      hypertrophy.
AB  - The induction of the atrial natriuretic factor (ANF) gene during alpha 1
      adrenergic stimulation of neonatal rat ventricular myocytes has served as a model
      for gene expression during cardiac muscle cell hypertrophy. This study describes
      and identifies a single regulatory element that mediates expression of the ANF
      gene. Deletional mutations were generated in a 639-bp fragment of the ANF
      promoter that confers alpha 1-adrenergic inducibility to a luciferase reporter
      gene in transient transfection assays in ventricular myocytes. The results of gel
      mobility shift and diethylpyrocarbonate (DEPC) interference studies with nuclear
      cardiac cell extracts identified the nucleotide contract points for a novel A/T
      rich element (ANF-AT) at positions -582/-575 that partially mediates alpha 1
      adrenergic inducibility. Mutations in the ANF-AT element reduced alpha-adrenergic
      inducibility of an ANF-TK-luciferase fusion gene in cardiac cells by 35% but had
      no effect on expression in other muscle and non-muscle cells tested. Gel mobility
      supershift assays with antibodies directed against the MEF-2 protein, the
      homeobox protein MHox, or the zinc finger protein HF-1b, document that these
      factors are not major components of the endogenous ANF-AT binding activity in
      cardiac muscle cells. The current study provides evidence for a role for a novel
      A/T-rich element in the regulation of ANF gene expression in cardiac ventricular
      myocytes.

PMID- 9140812
TI  - Stimulation of carbohydrate metabolism reduces hypothermia-induced calcium load
      in fatty acid-perfused rat hearts.
AB  - In the present study we examined the impact of glycolysis and glucose oxidation
      on myocardial calcium control and mechanical function of fatty acid-perfused rat
      hearts subjected to hypothermia rewarming. One group (control) was given glucose
      (11.1 mM) and palmitate (1.2 mM) as energy substrates. In a second group
      glycolysis was inhibited by iodoacetate (IAA, 100 microM) and replacement of
      glucose with pyruvate (5 mM), whereas in the third group glucose oxidation was
      stimulated by administration of dichloroacetate (DCA, 1 mM) and insulin (500
      microU/ml). All groups showed a rise in myocardial calcium ([Ca]total in response
      to hypothermia (10 degrees C). However, [Ca]total was significantly lower both in
      IAA- and DCA-treated hearts, as compared to controls (2.20 +/- 0.22 and 2.94 +/-
      0.20 v 3.83 +/- 0.29 nmol/mg dry wt., P < 0.025). The reduced calcium load in the
      treated hearts was correlated with higher levels of high energy phosphates.
      Following rewarming control and DCA-treated hearts still showed elevated
      [Ca]total, whereas IAA-treated hearts [Ca]total was not different from the pre
      hypothermic value. All groups showed a reduction in cardiac output following
      rewarming. Furthermore, the control group, in contrast to both IAA- and DCA
      treated hearts, showed a significant reduction in systolic pressure. These
      results show that hypothermia-induced calcium uptake in glucose and fatty acid
      perfused rat hearts was reduced by two different metabolic approaches: (1)
      inhibition of glycolysis by IAA while simultaneously by-passing the glycolytic
      pathway by exogenous pyruvate: and (2) stimulation of glucose oxidation by DCA.
      Thus, glycolytic ATP is not an essential regulator of sarcolemmal calcium
      transport under the present experimental conditions. Instead, we suggest that a
      change in oxidative substrate utilization in favour of carbohydrates may improve
      myocardial calcium homeostasis during hypothermia and rewarming.

PMID- 9140810
TI  - Effect of ATP depletion on kinetics of Na/Ca exchange-mediated Ca influx in Na
      loaded heart cells.
AB  - The kinetics of Ca influx by Na/Ca exchange into adult rat heart cells loaded
      with Na and depleted of ATP were investigated, to further elucidate how ATP
      regulates exchanger properties in the intact heart cell. We found an eight-fold
      reduction in Vmax for Ca uptake by ATP depletion, with no significant change in
      the K(m) for extracellular Ca or the K1 for inhibition by extracellular Na.
      Autoradiography of ATP depleted cells after45Ca uptake showed no gross
      heterogeneity of Ca uptake, as would occur if a small fraction of cells still
      retained some ATP. We conclude that the reduction in Vmax is a property of all of
      the ATP depleted cells. These kinetics are consistent with regulation of the
      putative calmodulin binding site on the exchanger. They are also consistent with
      sequestration of the exchanger at the intracellular face of the sarcolemma by
      intracellular Na dependent inactivation, a property of the exchanger observed in
      membrane patches to be relieved by ATP. However, no effect of heptalysine was
      observed on exchange activity in cells with ATP, nor was the restoration of
      exchange activity to ATP depleted cells by ATP resynthesis blocked by
      heptalysine. This suggests that in intact cells the activation of exchange
      activity by ATP is not caused by phosphatidylserine translocation to the
      cytosolic leaflet of the sarcolemma. Also, no effect of cytochalasin D was
      observed on exchanger activity or kinetics, in contrast with observations in
      Chinese hamster ovary (CHO) cells transfected with bovine cardiac Na/Ca exchanger
      by ATP, and these are differently expressed depending on the exchanger
      environment.

PMID- 9140813
TI  - Cardioprotection by cyclosporine A in experimental ischemia and reperfusion-
      evidence for a nitric oxide-dependent mechanism mediated by endothelin.
AB  - The acute effect of cyclosporine A (CSA) on myocardial function after ischemia
      and reperfusion and the mechanism of action was investigated in isolated working
      guinea-pig hearts. Myocardial function was experimentally infringed by imposing
      short-term global ischemia and reperfusion (15 min each). External heart work
      (EHW), determined before and after ischemia, served as the criterion for
      quantitation of recovery. Control hearts were perfused with modified Krebs
      Henseleit buffer, other hearts received buffer supplemented with CsA +/- an
      endothelin receptor antagonist or exogenous endothelin +/- an inhibitor of nitric
      oxide (NO) synthesis. To assess the importance of endothelial production of
      mediators directly, NO release in coronary effluent (continuously measured with
      an amperometric sensor) and release of 6-keto-prostaglandin F1, (6-keto-PGFb), a
      stable metabolite of prostacyclin (PGI2), were determined in non-working.
      Langendorff hearts. Oxidative stress during reperfusion was assessed by measuring
      glutathione release in coronary venous effluent. Cyclosporine A (0.8 microM)
      improved post-ischemic function significantly (59% recovery of EHW nu 31% for
      controls). At 0.08 microM. CsA was without beneficial effect (30% recovery). The
      endothelin (ET)A- and ETB-receptor antagonist bosentan inhibited the protective
      action of 0.8 microM CsA (32% recovery). Exogenous ET-1 (80 pM) improved recovery
      to 53%, an effect which was blocked by the inhibitor of NO-synthase, NG-nitro-L
      arginine (NOLAG. 1 microM. 31% recovery. In the control group, post-ischemic NO
      release in coronary effluent recovered from zero to about 100% of the pre
      ischemic value by 10 min. but then decreased rapidly during the subsequent 15 min
      of reperfusion. In hearts treated with 0.8 microM CsA, NO release stayed at 100%
      of the pre-ischemic value throughout reperfusion, the difference between controls
      and CsA-treated hearts being significant after 20 min of reperfusion. On the
      other hand, coronary venous release of 6-keto-PGF1a was not different between the
      groups. Release of glutathione during early reperfusion first 5 min) was
      significantly lowered (P < 0.05) to about 50% in CsA (0.8 microMI- and ET-I
      treated compared with controls (8.8 nmol/min). Cyclosporine A acts as a
      cardioprotective agent in our model of ischemia and reperfusion, presumably by
      elevating the level of endogenous nitric oxide and thereby reducing oxidative
      stress.

PMID- 9140815
TI  - Role of thyroid hormone and insulin in control of cardiac isomyosin expression.
AB  - Previous studies show that both diabetes and thyroid state exert a strong
      regulatory influence on the pattern of rodent cardiac isomyosin expression.
      Therefore, we determined the separate and combined effects of thyroid hormone
      (T3) and insulin treatment on rodent cardiac myosin heavy chain (MHC) expression
      using a model of combined thyroid deficiency (Tx) and diabetes (D). The
      combination of Tx and D completely transformed cardiac isomyosin expression such
      that the fast alpha-myosin heavy chain (MHC) was completely repressed at both the
      protein and mRNA level of expression; whereas, the slow beta-MHC was upregulated
      to constitute 100% of the total MHC pool, based on both protein and mRNA
      analyses. Daily low doses of exogenous T3 treatment (3 micrograms/kg b.w. i.p.).
      in the absence of insulin treatment, partially restored expression of the alpha
      MHC, while inhibiting expression of the beta-isoform. In contrast daily insulin
      treatment (4 U/rat), in the absence of exogenous T3 treatment, failed to exert
      any significant influence on the pattern of isomyosin expression in the thyroid
      deficient diabetic rat model. Furthermore, when exogenous T3 was administered in
      conjunction with insulin, the effect on MHC mRNA expression was greater than that
      of T3 alone, thus suggesting the existence of interaction between T3 and insulin
      action in the regulation of MHC mRNA expression. Collectively, these findings
      suggest that: (a) thyroid state is a dominant regulator of cardiac isomyosin
      phenotype: and (b) insulin does not exert any regulatory influence on cardiac MHC
      expression in a severe thyroid deficient state, instead it requires a critical
      level of circulating T3 in order to be effective in blunting MHC transformation
      associated with diabetes. It is thus concluded that the regulation of cardiac MHC
      by insulin is a complex mechanism involving interaction of insulin with
      subcellular factors likely to have impact on the specific action of T3. This
      interaction is disrupted in the absence of sufficient thyroid hormone.

PMID- 9140814
TI  - Beta-adrenoceptor-linked signal transduction in ischemic-reperfused heart and
      scavenging of oxyradicals.
AB  - In order to examine the mechanisms of ischemia-reperfusion induced changes in
      beta-adrenoceptor-linked signal transduction pathway, isolated rat hearts
      perfused in the absence or presence of superoxide dismutase (SOD) plus catalase
      (CAT) were made ischemic for 30 min and then reperfused for 60 min. The left
      ventricular developed pressure as well as the rare of contraction and rate of
      relaxation were markedly decreased, whereas the left ventricular end-diastolic
      pressure increased in the ischemic hearts. A significant increase in the density
      and affinity of beta 1-adrenoceptors without any changes in the characteristics
      of beta 2-adrenoceptors was evident in cardiac membranes obtained from the
      ischemic hearts. The recovery of contractile abnormalities in the ischemic heart
      was depressed upon reperfusion; the ischemic-reperfused hearts also showed
      attenuated inotropic responses to isoproterenol. The affinities and densities of
      beta- and beta-adrenoceptors were decreased in the ischemic-reperfused hearts;
      the magnitude of changes in beta 1-adrenoceptors was greater than that in beta 2
      adrenoceptors. The isoproterenol-stimulated adenylyl cyclase activity was
      depressed in both ischemic hearts and ischemic-reperfused hearts. The basal and
      forskolin-stimulated adenylyl cyclase activities were unaltered due to ischemia
      but were increased upon reperfusion. The NaF- and 5'-Guanylyl
      imidodiphosphate[Gpp(NH)p]-stimulated adenylyl cyclase activities were depressed
      in the ischemic hearts and increased in the ischemic reperfused hearts. Cholera
      toxin (CT)-stimulated adenylyl cyclase as well as the CT-catalysed ADP
      ribosylation activity and stimulatory G protein (Gs protein) immunoreactivity
      were decreased in the ischemic hearts and increased in the reperfused hearts.
      Pertussis toxin (PT)-stimulated adenylyl cyclase activity was unaltered in both
      ischemic and ischemic-reperfused hearts, whereas the PT-catalysed ribosylation
      and inhibitory G protein (Gi protein) immunoactivity were slightly increased in
      the reperfused myocardium. Thus the inability of isoproterenol to stimulate
      adenylyl cyclase in the ischemic-reperfused hearts may be due to alterations
      mainly in the characteristics of beta 1-adrenoceptors including density, affinity
      and coupling with the adenylyl cyclase. Scavenging of oxyradicals by the addition
      of SOD plus CAT in the perfusion medium prevented the reperfusion-induced changes
      in contractile function, inotropic responses of the heart to isoproterenol,
      activation of adenylyl cyclase by isoproterenol, as well as densities and
      affinities of beta-adrenoceptors in cardiac membranes. These results suggest that
      the depressed contractile activity and the attenuated inotropic responses of
      ischemic-reperfused hearts to isoproterenol as well as the defects in beta
      adrenoceptor-linked signal transduction may be due to the formation of
      oxyradicals in the myocardium.

PMID- 9140816
TI  - Altered expression of atrial natriuretic peptide and contractile protein genes in
      hypertrophied ventricle of JVS mice with systemic carnitine deficiency.
AB  - To characterize cardiac hypertrophy in juvenile visceral steatosis (JVS) mice
      with systemic carnitine deficiency, we investigated how the hypertrophy develops
      and whether it is associated with altered expression of any specific genes,
      especially atrial natriuretic peptide (ANP) and contractile protein genes, in the
      hypertrophied ventricle. Cardiac hypertrophy in JVS mice became apparent at 10
      days after birth and progressed during development. The hypertrophy was observed
      in the ventricles but not in the atria. ANP mRNA was more intensively expressed
      in JVS ventricles than in control even at 5 days. Carnitine administration
      ameliorated the cardiac hypertrophy and suppressed the augmentation of ANP mRNA
      in the ventricles. Isoform change of expression of alpha-actin genes from cardiac
      to skeletal was seen in the ventricles of JVS mice at 2 weeks. There was no
      difference in the ratio of beta-myosin heavy chain mRNA to alpha-myosin heavy
      chain mRNA between control and JVS mice at 5 days, but at 2 weeks the ratio was
      significantly lower in JVS mice than in control. These results suggest that the
      molecular characteristics of cardiac hypertrophy caused by carnitine deficiency
      are different from those of cardiac hypertrophy caused by aortic constriction.

PMID- 9140817
TI  - Sympathetic modulation of the effect of nifedipine on myocardial contraction and
      Ca current in the rat.
AB  - The regulation of cardiac L-type Ca2- current (Ica) and contraction by
      dihydropyridine antagonists and beta-adrenergic receptor agonists has been the
      subject of numerous studies over the last decade. However, little is known on the
      crosstalk between these two regulatory pathways. For instance, a fundamental
      question that remains unanswered is: does activation of the beta-adrenergic
      receptors modify the sensitivity of the myocardium to dihydropyridine agonists?
      To answer this question, we examined in the present study how activation of the
      beta-adrenergic receptors modifies the effects of nifedipine on the mechanical
      and energetic parameters of the isolated perfused rat heart. Activation of the
      beta-adrenergic receptors was achieved by perfusing the hearts with isoprenaline,
      a non-selective beta-adrenergic receptor agonist, and could be reduced by
      atenolol, a beta-adrenergic receptor antagonist. To examine possible alterations
      during hypertension in the sensitivity of the hearts to the drug, tested, the
      study was performed in both normotensive Wistar-Kyoto (WKY) and spontaneously
      hypertensive animals (SHR). While 0.1 microM nifedipine reduced left ventricular
      pressure (LVP) by 36% and 34% in WKY and SHR rats, respectively, under basal
      conditions, its effects became negligible in both groups of rats after
      stimulation of the hearts with 0.1 microM isoprenaline. Addition of 1 microM
      atenolol in the presence of isoprenaline restored the inhibitory effect of
      nifedipine to control values in both WKY and SHR rats. Additional experiments
      were performed in isolated ventricular myocytes from WKY rats using the whole
      cell patch-clamp technique. The inhibitory effects of 0.1 to 1 microM nifedipine
      were significantly larger on basal Ica than after the current had been previously
      elevated by 0.1 microM isoprenaline. Addition of 1 microM atenolol in the
      presence of isoprenaline partially restored the inhibitory effect of nifedipine
      on Ica. Our results demonstrate a reduced sensitivity of the heart muscle to
      nifedipine during activation of beta 1-adrenergic receptors. This effect is
      partly explained by a reduced inhibitory effect of nifedipine on Ic during
      activation of cAMP-dependent phosphorylation.

PMID- 9140818
TI  - The effect of age on adenosine A1 receptor function in the rat heart.
AB  - Adenosine is an important regulatory metabolite in the heart where it has a
      cardioprotective function. In the ventricle, the cardioprotective action of
      adenosine is mediated through the adenosine A1 receptor and inhibition of
      adenylyl cyclase. In order to investigate the effect of age on adenosine signal
      transduction in the heart, the effect of specific adenosine A receptor agonists
      on adenylyl cyclase activity was measured in crude cardiac ventricular membranes
      isolated from 1-, 6- and 24-month-old Fisher 344 rats. There were no differences
      in basal cyclase activity with age. Consistent with observations from other
      laboratories, isoproterenol- and forskolin-stimulated cyclase activity decreased
      with age. In addition, there was an age-related decline in the capacity of
      adenosine to inhibit stimulated adenylyl cyclase. The specific A1 adenosine
      receptor agonists, N6-cyclopentyladenosine (CPA) and N6-p-sulfophenuladenosine
      (SPA) inhibited isoproterenol- and forskolin-stimulated adenylyl cyclase activity
      in cardiac membranes from 1-month and 6-month-old rats; however, CPA and SPA did
      not inhibit adenylyl cyclase in membranes from 24-month-old rats. These data
      indicate that in addition to the age-related decline in beta-adrenergic receptor
      function with age, there is also a decrease in adenosine A; receptor-mediated
      responses. In contrast, carbachol acting through muscarinic receptors, caused the
      same inhibition of adenylyl cyclase at all ages. Therefore, the age-related
      decline in inhibitory signal transduction is specific to the adenosine A1
      receptor. The age-related defect is probably at the level of the
      adenosine/receptor interaction and/or the receptor/guanine nucleotide binding
      protein interaction.

PMID- 9140819
TI  - Ontogeny of regulatory mechanisms for beta-adrenoceptor control of rat cardiac
      adenylyl cyclase: targeting of G-proteins and the cyclase catalytic subunit.
AB  - Fetal and neonatal tissues are resistant to catecholamine-induced desensitization
      of essential physiological responses. We examined the mechanisms underlying the
      ontogeny of desensitization in neonatal rat heart for the beta-adrenergic
      receptor/adenylyl cyclase signaling cascade. Animals of different ages received
      isoproterenol daily or 4 days and cardiac membrane preparations were evaluated on
      the 5th day (6, 15, 25 days old and adults). Measurements were made of basal
      activity, activity stimulated by two agonists (isoproterenol or glucagon) that
      operate at different receptors but that share Gs as the transduction
      intermediate, or by forskolin-Mn' to assess total catalytic capacity of the
      cyclase subunit; we also assessed inhibition of activity by carbachol which acts
      via muscarinic cholinergic receptors and G. Adult rats exhibited robust
      desensitization of the adenylyl cyclase response but the effect was heterologous
      in that equivalent loss of activity was seen for basal, isoproterenol- and
      glucagon-stimulated activity forskolin-Mn(2+)-stimulated activity was also
      decreased. Two factors contributed to desensitization; generalized reduction in
      membrane protein concentrations caused by cell enlargement (reduced surface-to
      volume ratio), and specific interference with the G-protein component that
      couples receptors to the cyclase. Thus, after adjustment for changes in membrane
      protein, the desensitization of the forskolin-Mn2, response was no longer
      evident, but the effects on the other measures were still present. In addition,
      isoproterenol treatment produced crosstalk with the carbachol/Gi signaling
      pathway, with significant reductions in the ability of carbachol to inhibit
      adenylyl cyclase activity. Heterologous desensitization by isoproterenol was also
      present in 15 and 25 day old rats, but involved only selective components of the
      effects seen in adults. At 25 days, uncoupling of signals operating through Gs
      and Gi was obtained without a reduction in forskolin-Mn(2+)-stimulated activity.
      At 15 days, only the effect on Gs coupling was seen. At 6 days, agonist-induced
      desensitization was not detectable and instead, heterologous sensitization was
      found. In these youngest animals, isoproterenol treatment produced a parallel
      increase in basal, isoproterenol-, glucagon- and forskolin-Mn(2+)-stimulated
      activity, unaccompanied by changes in membrane protein concentrations, indicating
      an increase in adenylyl cyclase catalytic activity. These results indicate that
      the ability to elicit desensitization is not an inherent property of cardiac
      cells but rather is acquired in distinct stages during development. Sensitization
      by agonists early in development may be important in preserving physiological
      responsiveness during ontogenetic surges of adrenergic activity.

PMID- 9140820
TI  - Evidences of antagonism between amiodarone and triiodothyronine on the K+ channel
      activities of cultured rat cardiomyocytes.
AB  - Effects of acute and chronic treatments with amiodarone, both in the presence and
      the absence of exogenous triiodothyronine (T3), on repolarizing outward K+
      currents were investigated by patch-clamp technique in cultured newborn rat
      ventricular cells. Acute exposure to amiodarone dose-dependently inhibited the
      transient outward (Ito IC50 = 4.9 microM) and the steady-state outward (IK, IC50
      = 6.3 microM) K4 currents. The dose-response curve of this acute inhibitory
      action was unaffected by the presence of T3. When amiodarone was applied
      chronically. 72-h exposure to a low dose of the drug (1 microM) significantly
      decreased the current densities of Ito and I kappa for the cells cultured in a
      serum-supplemented medium containing 0.12 nM T3. In a serum-free medium without
      T3o chronic amiodarone treatment revealed null effect on either Ito or IK. In
      addition, 72-h in-vitro treatment with Ti enhanced the current densities of both
      Ito (EC50 = 0.13 nM) and I kappa (EC50 = 0.33 nM). Concentration-response
      analysis indicated that amiodarone (1 microM) showed competitive inhibition
      towards the action of T3 on Ito but noncompetitive inhibition towards the action
      of T3 on IK. These results suggest that different ionic mechanisms are produced
      by acute and long-term treatments with amiodarone. The latter showed T3-dependent
      inhibition of cardiac Ito and IK. When chronically administered, amiodarone may
      antagonize T3 and thereby counteract its hormonal effect on K+ channels. This
      implies that, at the myocyte level, antagonism of the action of thyroid hormones
      in K+ channel activities may contribute to the cardiac effects of chronic
      amiodarone therapy.

PMID- 9140821
TI  - Developmental changes in rat cardiac DNA, RNA and protein tissue base:
      implications for the interpretation of changes in gene expression.
AB  - During cardiac development the expression levels of many genes change as
      determined by Northern blot, dot blot, RNase protection, quantitative RT-PCR.
      Western blot or immunoprecipitation analyses. It is not always realized that the
      total amount of RNA or protein per gram of heart, dubbed tissue base, may change
      significantly during development as well. If this would be the case, this has to
      be taken into account. So far, the (changing) tissue base has not been
      established during cardiac development. To this end developmental profiles of
      cardiac DNA, RNA and protein concentration were determined in rats ranging in age
      from embryonic day 13 until neonatal day 121. The profiles show significant
      development changes in each parameter, that closely match the distinct growth
      phases of the developing heart and provide the parameters that are essential for
      an adequate interpretation of changes in the amount of a distinct mRNA and/or
      protein. In a comparison between in situ hybridization and Northern blot analysis
      it is demonstrated that the same developmental profile leads to an almost
      opposite conclusion depending on whether or not the changing tissue base is taken
      into account. These findings are of great interest for studies aimed at
      unravelling the molecular mechanisms underlying the regulation of gene expression
      during cardiac development.

PMID- 9140823
TI  - Differences in reperfusion length following 30 minutes of ischemia in the rabbit
      influence infarct size, as measured by triphenyltetrazolium chloride staining.
AB  - Assessment of myocardial infarct size in acute experimental models is usually
      done by triphenyltetrazolium-chloride (TTC) staining. A certain period of
      reperfusion is mandatory for discrimination of the infarct zone, especially after
      relatively short ischemic periods. However, it is unclear what the optimal
      reperfusion time is for full delineation of the infarct following 30 min of
      myocardial ischemia in the rabbit. This study compares infarct size, assessed by
      TTC, in anesthetized open-chest rabbits subjected to 30 min of coronary artery
      occlusion followed by either 2 (n = 14) v 4 (n = 14) (protocol 1), or 3 (n = 8) v
      6 (n = 7) h of reperfusion (protocol 2). Area at risk was assessed by blue dye
      and necrotic zone by TTC staining. Protocol 1: heart rate and mean blood pressure
      were comparable in both groups throughout the protocol. Regional myocardial blood
      flows in both the ischemic and non-ischemic zones during ischemia and after 2 h
      of reperfusion were comparable between the groups. Regional myocardial blood flow
      in the post-ischemic zone deteriorated between 2 and 4 h (1.11 +/- 0.15 v 0.58 +/
      0.09 ml/min/g, respectively, P = 0.0004) of reperfusion. The size of the area at
      risk was comparable (0.31 +/- 0.03 v 0.33 +/- 0.03 of the LV weight in the 2 and
      4 h reperfusion groups). However, the ratio of the necrotic zone to the ischemic
      zone at risk was 63% larger in the 4 compared to the 2 h of reperfusion group
      (0.31 +/- 0.04 v 0.19 +/- 0.05, respectively, P = 0.02). Analysis of covariance
      performed on the weight of tissue that developed necrosis and the weight of
      ischemic zone at risk revealed a significant effect of the reperfusion time (P =
      0.014). Protocol 2: there was no difference in infarct size between rabbits
      subjected to three (0.38 +/- 0.05 of the area at risk) v 6 h (0.41 +/- 0.07) of
      reperfusion (P = 0.72). Analysis of covariance performed on the weight of tissue
      that developed necrosis and the weight of ischemic zone at risk did not reveal a
      significant effect of the reperfusion time. Infarct size as assessed by TTC
      following 30 min of myocardial ischemia, is smaller when measured 2 h after
      reperfusion than after 4 h of reperfusion. At least 3 h of reperfusion is needed
      to delineate infarct size by tetrazolium staining following 30 min of ischemia.

PMID- 9140822
TI  - Peptides derived from cardiovascular G-protein-coupled receptors induce
      morphological cardiomyopathic changes in immunized rabbits.
AB  - An experimental model of early-stage cardiomyopathy was created by immunizing
      rabbits for 1 year with synthetic peptides corresponding to the sequence of the
      second extracellular loop of either beta-adrenoceptors or M2-muscarinic
      receptors. Thirty male rabbits were used and divided into three groups: a control
      group (n = 10), a group immunized with the peptide corresponding to the beta
      adrenoceptor (beta 1 group) (n = 10) and a group immunized with the peptide
      corresponding to the M2-muscarinic receptor (M2 group) (n = 10). If the sera from
      both groups of immunized rabbits high-titres of anti-peptide antibodies were
      found throughout the study period but not in the sera from control rabbits or in
      the preimmune sera of immunized rabbits. No significant cross-reaction with
      peptides other than those used for immunization was found. The myocardial
      receptor density of both immunized groups displayed a strong trend toward
      receptor up-regulation. This was significant in the beta 1 group but not in the
      M2 group. Both groups of immunized rabbits displayed significantly enlarged
      ventricles and thinner walls, as compared with the control group. However, in
      contrast to the beta 1 group, which showed enlarged cavities in both left and
      right ventricles, the M2 group was mainly affected in the right ventricles.
      Moreover, morphological examinations of the hearts of rabbits from both immunized
      groups demonstrated focal myofibrillar lysis, loss of myofilament, mitochondrial
      swelling and condensation, sarcoplasmic vacuolation, deposition of dense granules
      in the sarcoplasm and the myofibrils. One of the sex control rabbit hearts which
      were examined showed mild degenerative changes in the myocardium and scant
      mononuclear cell infiltration. However, when all the control rabbit hearts were
      examined by electron microscopy, no significant alterations were found. These
      results suggest that immunization by peptides, corresponding to the target
      sequences for anti-receptor autoantibodies in idiopathic dilated cardiomyopathy,
      induces morphological changes in the heart similar to those found in the human
      disease.

PMID- 9140824
TI  - Isometric tension and mutant myosin heavy chain content in single skeletal
      myofibers from hypertrophic cardiomyopathy patients.
AB  - Several mutations in the beta-myosin heavy chain (beta-MHC) gene have been linked
      to hypertrophic cardiomyopathy (HCM). Because this gene is also expressed in slow
      twitch fibers of skeletal muscle, we have been able to study the mutant beta
      myosin content and mechanical properties associated with these myosin mutations
      in single skinned skeletal muscle fibers obtained from HCM patients. We found
      that in patients carrying the 403Arg-->Gln mutation, the mutant beta-MHC
      comprises 47.3 +/- 9.1% of the total beta-MHC present in single slow-twitch
      fibers. Therefore, both alleles of the beta-MHC gene are on average equally
      expressed. Isometric tension was decreased by 18% in slow fibers from HCM
      patients with the 403Arg-->Gln mutation, but was unchanged in slow fibers from
      patients with two other beta-MHC gene mutations. Taken together with the previous
      demonstration of reduced velocities generated by these myosins in an in vitro
      assay, our results suggest that the mutant beta-myosins are functional molecular
      motors that are able to generate tension and movement, but with abnormal
      kinetics.

PMID- 9140825
TI  - Effects of exogenous and endogenous nitric oxide on the contractile function of
      cultured chick embryo ventricular myocytes.
AB  - Nitric oxide (NO) has been shown to be a ubiquitous intercellular autacoid in the
      heart and, in cultured rat ventricular myocytes, to decrease the contractile
      responsiveness to isoproterenol (ISO). The aim of the present study was to
      investigate whether exogenous (sodium nitroprusside, SNP) or endogenous nitric
      oxide generated from L-arginine modulated the response to ISO in cultured chick
      embryo ventricular myocytes. SNP 1 microM or L-arginine 1 mM had no effect on
      baseline contractile function. Superfusion with ISO 100 nM significantly
      increased myocyte amplitude of shortening to 1.31 +/- 0.06 (ratio to baseline
      amplitude). Initial superfusion with SNP 1 microM or L-arginine 1 mM attenuated
      the response to ISO to 0.89 +/- 0.05 and 1.09 +/- 0.07 respectively (P < 0.05).
      Potassium ferrocyanide which is not a NO donor and D-arginine the inactive
      substrate of NO synthase did not attenuate the response to ISO. Myocyte cGMP
      content was significantly increased by incubation with SNP 1 microM (31.65 +/- 3
      fmol/well) but not by L-arginine 1 mM (11.1 +/- 0.3 fmol/well) as compared to
      myocytes incubated in control medium (11 +/- 0.9 fmol/well). Preincubation with
      SNP 1 microM or L-arginine 1 mM significantly attenuated the ISO mediated
      increase in cAMP content from 4.33 +/- 0.2 pmol/well (ISO 100 nM alone) to 1.48
      +/- 0.36 fmol/well and 1.72 +/- 0.21 pmol/well respectively. Potassium
      ferrocyanide and D-arginine had no effect on myocyte cGMP or cAMP content. Chick
      embryo myocytes have measurable and LNMMA-inhibited NO synthase activity as
      measured by the conversion of [3H] L-arginine to [3H] L-citrulline. In
      conclusion, these results demonstrate that in cultured chick embryo ventricular
      myocytes both exogenous and endogenous NO elevate cGMP. This may account for the
      inhibition of beta-adrenergic agonist-stimulated increases in cAMP and amplitude
      of shortening via an unidentified intracellular negative coupling.

PMID- 9140826
TI  - ATP-activated cationic current in rabbit sino-atrial node cells.
AB  - The electrophysiological effect of extracellular ATP was investigated in voltage
      clamped single cells from the rabbit sino-atrial node. External 0.5 mM ATP
      consistently activated a time-independent, weakly inwardly rectifying current
      (2.26 +/- 0.14 pA/pF at -100 mV, n = 23). This external ATP-activated current
      increased in a dose-dependent manner over the concentration range 0.01 to 1 mM
      ATP. However, non-hydrolysable ATP analogs (a, beta-methylene ATP and beta,r
      methylene ATP) failed to activate this current. Moreover, adenosine, adenosine
      monophosphate and adenosine diphosphate were all ineffective in eliciting the ATP
      activated current over the concentration range 0.5 to 1 mM, suggesting that it is
      regulated via the P2-purinoreceptor. The permeability sequence for the ATP
      activated current among different cations (determined from reversal potential
      measurements) was 1.09: 1: 1: 0.24: 0.22 for K+, Na+, Cs+, Tris and N-methyl-D
      glucamine. The current component was not affected by substitution of external Cl-
      by aspartate or by the application of a stilbene-derivative Cl- channel blocker.
      Thus, the ATP-activated current in rabbit sino-atrial node cells was non
      selective for monovalent cations, and could be carried by large molecular ions,
      such as N-methyl-D-glucamine or Tris. We suggest that it might make some
      contribution to the chronotropic effects seen on release of transmitters from
      autonomic nerve endings in the heart.

PMID- 9140828
TI  - Distinct components of morphine effects on cardiac myocytes are mediated by the
      kappa and delta opioid receptors.
AB  - Morphine exerts direct effects on cultured cardiac myocytes from neonatal rats.
      These effects are mediated via the delta and the kappa opioid receptors, as mu
      opioid receptors are not present in neonatal cardiomyocyte cultures. Binding
      parameters to the delta and kappa opioid receptors were determined in membrane
      preparations from these cultures by heterologous competition to [3H]diprenorphine
      binding, with [D-Pen2, D-Pen5]-enkephalin (DPDPE) and trans-(dl)-3, 4-dichloro-N
      methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide methanesulfonate (U
      50,488H) as specific displacers respectively. To define the components of
      morphine effects mediated via activation of either the delta or the kappa opioid
      receptor alone, cardiac myocytes were exposed to morphine in the presence of
      specific antagonists to the kappa or delta opioid receptor respectively.
      Activation of the kappa opioid receptors by morphine caused a transient increase
      in Ca2+ influx, leading to increase in amplitudes of [Ca2+]i transients and
      contraction, with no change in the intracellular pH. Activation of the delta
      opioid receptors alone by morphine caused a decrease in the amplitude of
      contraction. This decrease was mediated by a decrease in the intracellular pH
      leading to reduced responsiveness of the myofilaments to Ca2+. There was no
      change in Ca2+ influx and in the amplitude of [Ca2+]i transients. The effects
      mediated through the delta opioid but not through the kappa opioid receptors were
      pertussis toxin sensitive, indicating coupling of the delta opioid receptors to
      pertussis toxin sensitive GTP-binding proteins. The overall effects of morphine
      on the neonatal cardiac myocytes were the sum of the effects exerted by morphine
      when it activated each of the opioid receptors alone.

PMID- 9140827
TI  - Effects of chronic angiotensin-converting enzyme inhibition on left ventricular
      and myocyte structure and function during recovery from chronic rapid pacing.
AB  - LV and myocyte function and angiotensin converting enzyme (ACE) activity with ACE
      inhibitor (ACEI) treatment were examined in four groups of dogs (n = 6 each): (1)
      control; (2) with 4 weeks of recovery from chronic rapid pacing (REC: 216
      beats/min), (3) ACEI for the first 14 days of REC (ACEI--14), and (4) ACEI for 28
      days of REC (ACEI--28). Three additional control dogs were administered ACEI for
      28 days. LV mass increased with REC compared to control (146 +/- 6 v 92 +/- 3 g,
      P < 0.05), was unaffected with ACEI--14, and was decreased with ACEI--28 compared
      to REC (111 +/- 8 g, P < 0.05). Myocyte function was decreased in REC compared to
      controls (43 +/- 3 v 63 +/- 3 microns/s, P < 0.05) and was similarly reduced with
      ACEI--14. However, with ACEI--28, myocyte shortening velocity was increased
      compared to REC (56 +/- 1 microns/s, P < 0.05). Myocyte beta-adrenergic response
      was decreased with REC and ACEI--14 compared to controls (53 +/- 9 and 57 +/- 14,
      respectively v 127 +/- 14 microns/s, P < 0.05). ACEI--28 resulted in a
      normalization of myocyte beta-adrenergic responsiveness (108 +/- 3 microns/s). LV
      myocardial ACE activity increased in REC compared to control (5.82 +/- 0.21 v
      3.51 +/- 0.15 nmol/mg/min, P < 0.05). With ACEI--14 or ACEI--28, myocardial ACE
      activity was decreased compared to REC (4.16 +/- 0.06 and 4.08 +/- 0.23
      nmol/mg/min; P < 0.05). In control dogs administered ACEI, there were no
      differences in any of these parameters compared to controls. The unique findings
      in this study were: (1) effects of ACEI treatment in this model of LV hypertrophy
      were time dependent with respect to LV mass and LV and myocyte function; and (2)
      the effect of ACEI treatment on the degree of LV hypertrophy appears to not be
      solely due modulation of myocardial ACE activity.

PMID- 9140829
TI  - Electrophysiology of rabbit ventricular myocytes following sustained rapid
      ventricular pacing.
AB  - The present study examined changes in electrophysiological properties of
      ventricular myocytes isolated from rabbit hearts after 2-3 weeks of rapid
      ventricular pacing. Left ventricular end-diastolic pressure at completion of the
      pacing period was nearly four-fold greater than in age-matched controls, although
      there was no significant change in heart weight/body weight ratio. Action
      potentials recorded in current-clamp mode at low stimulation frequencies were
      significantly longer in duration and phase 1 diminished in isolated myocytes from
      paced hearts compared with control. In voltage-clamp experiments. L-type Ca2+
      current (ICa) density was not different between groups of myocytes, but the
      maximum current (at + 10 mV) elicited by 10 microM isoproterenol was
      approximately 40% less in myocytes from paced hearts. In contrast, maximum ICa
      elicited by 10 microM forskolin was similar in both groups. The 4-aminopyridine
      sensitive transient outward current (Ito) was 65% less (at + 60 mV) in myocytes
      from paced hearts than from control. However, after approximately 24 h in
      culture, Ito density in these myocytes returned toward control values. Despite
      marked reduction in Ito density, the inward rectifier current (IK1) was not
      different between groups. These data demonstrate that Ito is significantly and
      reversibly decreased in myocytes from rapidly paced hearts, which may partly
      account for marked changes in action potential morphology. Although basal ICa was
      not altered in this group of myocytes compared with control, its modulation by
      beta-agonists was markedly blunted, probably through a decrease in receptor
      density or coupling to adenylyl cyclase. These changes in myocyte K+ and Ca2+
      channel behavior in paced hearts may relate to impaired contractility and
      arrhythmogenesis that is characteristic of the intact failing heart.

PMID- 9140830
TI  - Cardioprotective and anti-oxidant effects of the terpenoid constituents of Ginkgo
      biloba extract (EGb 761).
AB  - Hemodynamic and electron spin resonance analyses were used to assess the in vivo
      and in vitro cardioprotective and antioxidant effects of therapeutically relevant
      doses of Ginkgo biloba extract (EGb 761) and its terpenoid constituents
      (ginkgolides A and B, bilobalide) in the rat. Significant anti-ischemic effects,
      indicating improved myocardial functional recovery, were observed after repeated
      (15-day) oral treatments with both EGb 761 (60 mg/kg/day) and ginkgolide A (4
      mg/kg/day), as compared to placebo. In vitro pre- and post-ischemic perfusion of
      hearts in the presence of the ginkgolides A and B (both at 0.05 microgram/ml) or
      bilobalide (0.15 microgram/ml), but not EGb 761 (5 micrograms/ml), significantly
      improved all hemodynamic parameters. Post-ischemic levels of the 5,5-dimethyl-1
      pyrroline N-oxide (DMPO)/hydroxyl radical spin-adduct (DMPO-OH) in coronary
      effluents were significantly decreased after in vivo oral treatments or after in
      vitro perfusion with EGb 761 or the terpenes, the most effective compound being
      ginkgolide A. As the presence of the terpenes did not influence the formation of
      the superoxide/DMPO adduct or DMPO-OH in acellular tests with superoxide and
      hydroxyl radical generators, their cardioprotective effects appear to involve an
      inhibition of free radical formation rather than direct free radical scavenging.

PMID- 9140831
TI  - Reduction of myocardial myoglobin in bovine dilated cardiomyopathy.
AB  - Myoglobin levels are decreased in various animal models of heart failure, a
      change that has been associated with compromised energy supply. The underlying
      mechanisms by which myoglobin content decreases in failing myocardium are
      unknown. Bovine hereditary cardiomyopathy (bCMP) displays several characteristics
      of human dilated cardiomyopathy with a marked desensitization of the beta
      adrenoceptor signal cascade. The aim of the present study was to investigate
      whether a similar reduction of myoglobin can be seen in this animal model, and to
      elucidate the possible mechanism of this reduction. Myoglobin protein
      concentration was decreased by 46-47% (P < 0.05) in left and right ventricular
      myocardium of failing hearts (n = 9) compared to control hearts (n = 11). No
      difference was found between atria of diseased and control animals.
      Immunohistochemistry with a polyclonal antibody against myoglobin revealed a
      strong and uniform labeling in cardiomyocytes of non-failing hearts. Using
      microscopic densitometry, immunosignals were significantly decreased in
      ventricular myocytes of bCMP hearts (168 +/- 5.3 v 118 +/- 8.6 arbitrary units, P
      < 0.05). Moreover, myoglobin was heterogeneously distributed in bCMP hearts, with
      single myocytes showing no staining. Slot blot analysis of total RNA demonstrated
      a 40-50% reduction (P < 0.05) of myoglobin mRNA levels in ventricular but not in
      atrial myocardium of bCMP hearts. The results support the view that a decrease of
      myocardial myoglobin is a general phenomenon in end-stage heart failure. It
      appears to be primarily due to reduced gene expression but may be aggravated by
      leaking from single myocytes. The decrease of myoglobin may contribute to the
      imbalance between energy production and energy expenditure in heart failure.

PMID- 9140832
TI  - Cardiac sarcoplasmic reticular function in rats with chronic heart failure
      following myocardial infarction.
AB  - Sarcoplasmic reticular function of rats with chronic heart failure (CHF)
      following coronary artery ligation was examined. The coronary artery ligation
      produced 43% infarction of the left ventricle and increased left ventricular end
      diastolic pressure 8 weeks after the operation, suggesting the development of CHF
      by this period. The developed force transients of the skinned fiber of coronary
      artery-ligated rats were decreased when the skinned fiber was preloaded for 0.25
      0.5 min with 10(-5)M Ca2+ (53-70%) and when preloaded with 10(-6)M Ca2+ and then
      exposed to 0.1-1 mM caffeine (39-87%). The results suggest that the rate of Ca2+
      uptake by the sarcoplasmic reticulum (SR) and its ability to release Ca2+ were
      reduced in the failing heart. [3H]Ryanodine binding activities in homogenates and
      SR-enriched fractions were significantly reduced in the coronary artery-ligated
      group (32% and 21%, respectively). The results suggest that the amount of Ca2+
      released from SR decreased due to decreased Ca2+ uptake rate of SR and down
      regulation of the SR Ca(2+)-release channel, which contributes to cardiac
      dysfunction in failing hearts following acute myocardial infarction.

PMID- 9140833
TI  - Agonist-independent tonic inhibitory influence of Gi on adenylate cyclase
      activity in rabbit ventricular myocardium and its removal by pertussis toxin: a
      role of empty receptor-mediated Gi activation.
AB  - We evaluated whether Gi has a tonic inhibitory influence on myocardial adenylate
      cyclase (AC) in an agonist-independent way, and, if so, whether this is
      attributable to substantial coupling between agonist-free, empty inhibitory
      receptors and G. Rabbits received pertussis toxin (PTX, 10 micrograms/kg i.v.) 40
      h before preparing ventricular myocardial membranes, which was associated with
      virtually complete in vivo ADP-ribosylation and inactivation of the 41-kDa
      substrate. Pretreatment with PTX had no influence on basal AC activity but
      significantly enhanced AC activity elicited by 100 microM GTP. Furthermore, it
      markedly increased AC activity stimulated with 5'-guanylyl imidodiphosphate
      (GppNHp) and isoproterenol through a wide range of concentrations of these
      stimulants. These findings indicate that Gi has a tonic influence on he
      stimulatory effects of guanine nucleotides and beta-adrenoceptor stimulation on
      AC even in the absence of the inhibitory receptor agonists. The muscarinic
      receptor antagonists atropine and AF-DX 116 significantly enhanced isoproterenol
      stimulated AC activity, as PTX pretreatment did, except that statistically
      significant increasing effects of these antagonists on GppNHp-stimulated AC
      activity was observed only at higher concentrations of GppNHp. The enhancement by
      atropine was not detected in PTX-pretreated membranes. The selective beta 2
      adrenoceptor antagonist ICI 118,551 did not modify the stimulatory effects of
      guanine nucleotides and isoproterenol on AC in either control or PTX-pretreated
      membranes, excluding the possible involvement of beta 2-adrenoceptors in tonic
      activation of Gi. We conclude that Gi is tonically activated by agonist-free,
      empty muscarinic receptors, which leads to attenuation of Gs-mediated or beta
      adrenoceptor-mediated activation of AC. The potentiating effect of PTX
      pretreatment on GppNHp-stimulated AC activity may be at least partially due to
      the direct action of PTX on the Gi heterotrimeric complex, independently of the
      coupled receptors.

PMID- 9140834
TI  - Butanedione monoxime promotes voltage-dependent inactivation of L-type calcium
      channels in heart. Effects on gating currents.
AB  - The effect of 20 mM extracellularly applied 2,3-Butanedione monoxime (BDM) on L
      type Ca2+ channel charge movement current was studied in whole-cell voltage
      clamped guinea-pig ventricular myocytes. Intramembraneous charge movement in
      response to depolarizing pulses (charge 1), was reduced after the application of
      BDM. The effect was more pronounced at the OFF of the charge transient (41%) than
      at the ON (7%). The steady-state availability curve of charge 1 was shifted to
      the left; the magnitude of the voltage shift was similar to the shift in Ca2+
      current availability. Charge movement recorded in the negative voltage range
      (charge 2) after conditioning depolarizing pulses of different duration, was
      increased by BDM. For a 300-ms conditioning pulse charge 2 measured during a
      negative test pulse increased 40% (in Ba2+ external solution) or 35% (in Ca2+
      external solution). These results show that BDM promotes voltage-dependent
      inactivation of L-type Ca2+ channels in parallel with charge interconversion
      between intramembranous charges 1 and 2. Mechanistically they are consistent
      either with dephosphorylation or a dihydropyridine-like action, but argue against
      open channel block as the mechanism of the effect of the drug.

PMID- 9140835
TI  - Acute and chronic effects of adriamycin on fatty acid oxidation in isolated
      cardiac myocytes.
AB  - This study was designed to determine if acute (in vitro) or chronic (in vivo)
      adriamycin inhibits cardiac fatty acid oxidation and if so at what sites in the
      fatty acid oxidation pathway. In addition, the role of L-carnitine in reversing
      or preventing this effect was examined. We determined the effects of adriamycin
      in the presence or absence of L-carnitine on the oxidation of the metabolic
      substrates [1-14C]palmitate. [1(-14)C] octanoate. [1(-14)C]butyrate, [U
      14C]glucose, and [2(-14)C]pyruvate in isolated cardiac myocytes. Acute exposure
      to adriamycin caused a concentration- and time-dependent inhibition of carnitine
      palmitoyl transferase 1 (CPT 1) dependent long-chain fatty acid, palmitate,
      oxidation. Chronic exposure to (18 mg/kg) adriamycin inhibited palmitate
      oxidation 40% to a similar extent seen in vitro with 0.5 mM adriamycin. Acute or
      chronic administration of L-carnitine completely abolished the adriamycin-induced
      inhibition of palmitate oxidation. Interestingly, medium- and short-chain fatty
      acid oxidation, which are independent of CPT 1, were also inhibited acutely by
      adriamycin and could be reversed by L-carnitine. In isolated rat heart
      mitochondria, adriamycin significantly decreased oxidation of the CPT 1 dependent
      substrate palmitoyl-CoA by 50%. However, the oxidation of a non-CPT 1 dependent
      substrate palmitoylcarnitine was unaffected by adriamycin except at
      concentrations greater than 1 mM. These data suggest that after in vitro or in
      vivo administration, adriamycin, inhibits fatty acid oxidation in part secondary
      to inhibition of CPT 1 and/or depletion of its substrate, L-carnitine, in cardiac
      tissue. However, these findings also suggest that L-carnitine plays an additional
      role in fatty acid oxidation independent of CPT 1 or fatty acid chain length.

PMID- 9140836
TI  - Partial inhibition of protein synthesis by Pseudomonas exotoxin A deranges
      catecholamine sensitivity of cultured rat heart myocytes.
AB  - To elucidate cellular mechanisms of myocardial depression in Pseudomonas sepsis
      the effects of sublethal concentrations of P. aeruginosa exotoxin A--a main
      virulence factor--were studied in cultured neonatal rat cardiomyocytes. It is
      known that this toxin exerts its pathogenic effect by inhibition of protein
      synthesis via ADP-ribosylation and thereby inactivation of elongation factor 2
      (EF-2). Within 48 72 h, half maximal inhibition of protein synthesis occurs at 4
      10 ng/ml. The toxin prevents the beta-adrenoceptor(AR)-mediated myosin heavy
      chain isozyme shift (V3/V1), while the T3-induced myosin shift is not suppressed.
      While beta 1-AR-downregulation by excess of norepinephrine (NE) is not affected,
      protein synthesis-dependent receptor upregulation in the recover period after
      removal of NE is completely suppressed by P. aeruginosa exotoxin A. Thus, a non
      lethal, partial inhibition of global cellular protein synthesis by P. aeruginosa
      exotoxin A: (1) completely prevents beta 1-AR-mediated myosin isozyme shift and
      beta-AR upregulation: (2) sustains the cardiomyocytes in a catecholamine
      refractory contractile state in the recovery period after catecholamine
      desensitization: (3) suggests cellular mechanisms by which P. aeruginosa exotoxin
      A might impair heart function in Pseudomonas sepsis: and (4) may help reveal the
      possible influence of endogenous inhibitors of EF-2.

PMID- 9140837
TI  - Effect of angiotensin-converting enzyme two-week inhibition on renal angiotensin
      II receptors and renal vascular reactivity in SHR.
AB  - We recently reported that intrarenal vascular AT1 angiotensin II (ANG II)
      receptors are major determinants of the increased vascular resistance and
      reactivity to ANG II observed in the kidney of spontaneously hypertensive rats
      (SHR). We decided to test the hypothesis that, by modifying plasma ANG II levels
      by inhibiting the ANG II-converting enzyme (ACE) with captopril, we would modify
      intrarenal ANG II receptors, and therefore the renal vascular response to ANG II.
      Two approaches were taken: (1) radioligand binding assays were performed on
      membrane preparations of purified renal microvessels and glomeruli, with
      displacement of 125I-[Sar-Ile8]-ANG II by specific non-peptide antagonists of AT
      (losartan) and AT2 (PD 123319): (2) dose-response curves to ANG II on the
      isolated perfused kidney were studied. Two weeks of captopril treatment
      significantly reduced blood pressure (BP) and relative heart weight, and
      increased plasma renin activity. The binding assays showed that renal
      microvessels and glomeruli expressed a single receptor population (AT1) for ANG
      II. The density of glomerular AT1 was not modulated by captopril treatment (600
      +/- 174 v 573 +/- 97 fmol/mg protein in non-treated and treated SHR
      respectively); however. AT1 density on the intrarenal arteries increased 3-fold
      (55 +/- 20 v 154 +/- 30 fmol/mg protein in non-treated and treated SHR
      respectively. P < 0.05). Experiments with isolated perfused kidneys demonstrated
      that captopril did not improve the compliance of intrarenal vessels to high flow
      but increased their reactivity to ANG II (ED50 = 18 nM v 0.5 pM, P < 0.01). We
      conclude that treatment with an ACE inhibitor increases vascular reactivity to
      ANG II which may be mediated by an upregulation of renal vascular ANG II
      receptors.

PMID- 9140838
TI  - Age-dependent changes in the effects of endocardial endothelium on the
      contractile characteristics of its adjacent myocardium in rats.
AB  - Cardiac contractility and the ability of myocardium to respond to various stimuli
      have been shown to be age-related. Endocardial endothelium has been shown to
      modulate the performance of its adjacent myocardium, and it has been proven that
      these changes are reversible by increasing extracellular calcium. This study was
      designed to evaluate whether the effects of endocardial endothelium and their
      modifications with changing extracellular calcium were age-dependent. Experiments
      were carried out on left ventricular papillary muscles isolated from male Wistar
      rats belonging to three different age groups 7 weeks, 4 months, and 9 months old.
      Extracellular calcium concentration (0.7 to 5 mM) curves were conducted in
      papillary muscles with intact endocardial endothelium (+ EE) and after its
      removal (- EE) with Triton X-100. At a low extracellular calcium concentration
      (0.7 mM), total tension (TT), maximum rate of tension development (+ dT/dt), time
      to peak tension (TTPT), and time to half tension decline from maximum tension
      (RT1/2) increased with increasing age (P < 0.01). Increasing extracellular
      calcium concentration eliminated age-related differences in TT and RT1/2 did not
      affect TTPT and caused + dT/dt to increase to greater levels in 7-week-old as
      compared to 4-month-old myocardium. Endocardial endothelial removal (-EE) had a
      greater effect on contractile indices in younger rats. Increasing extracellular
      calcium concentration eliminated EE-mediated changes in contractile indices
      regardless of age. Thus, increasing extracellular calcium concentration had a
      greater effect in younger rats and after -EE. Increasing extracellular calcium
      from 0.7 to 2.5 mM increased total tension in 7-week-olds, between 56% +EE and
      131% -EE (P < 0.01): in 4-month-olds, from 29% +EE to 57% -EE (P < 0.01): and in
      9-month-olds. from 13% +EE to 23% -EE (P = 0.08). These results indicate that the
      contractile effects of endocardial endothelium are both age- and calcium
      dependent, with responsiveness to endocardial endothelium decreasing with age.
      Myocardial contractile characteristics also vary with age and these differences
      are only partially reversible with increasing extracellular calcium
      concentration.

PMID- 9140839
TI  - The influence of the angiotensin I converting enzyme genotype in familial
      hypertrophic cardiomyopathy varies with the disease gene mutation.
AB  - Familial hypertrophic cardiomyopathy is an autosomal dominant genetically
      heterogeneous disease characterized by a partial penetrance and variable
      expressivity. Previous studies showed that the extent of hypertrophy is
      influenced by the angiotensin I converting enzyme insertion/deletion (I/D)
      polymorphism. Recently, molecular genetic analysis revealed the existence of
      healthy carriers and that as many as a quarter of genetically affected
      individuals do not express the disease. This data prompted us to re-investigate
      the role of the angiotensin I converting enzyme polymorphism on hypertrophy by
      assessing both clinically affected individuals and healthy carriers. For this,
      several families with mutations in the cardiac myosin binding protein C or the
      beta-myosin heavy chain genes were analysed. The mean maximal intraventricular
      septum thickness was compared as a function of angiotensin I converting enzyme
      genotypes in all genetically affected individuals (n = 114), and in subsets of
      subjects carrying either a splice acceptor site mutation in the cardiac myosin
      binding protein C gene (n = 33), or various missense mutations in the cardiac
      beta-myosin heavy chain gene (n = 81) or finally, mutation in the Arg403 codon of
      the beta-myosin heavy chain gene (n = 54). Significant association between the D
      allele and hypertrophy was observed only in the case of Arg403 codon mutations
      (mean septum thickness for subjects with the DD genotype: 19.3 +/- 2.7 mm: with
      the ID genotype: 13.4 +/- 1.3 mm and with the II genotype: 11.0 +/- 0.9 mm; P <
      0.02). These results were confirmed by the chi 2 test showing an over
      representation of DD genotype in patients carrying an Arg403 codon mutation
      associated with septal hypertrophy (P < 0.05). Our data confirms that the
      angiotensin I converting enzyme genotypes can influence the phenotypic expression
      of hypertrophy and shows that this influence depends on the mutation, raising the
      concept of multiple genetic modifiers in familial hypertrophic cardiomyopathy.

PMID- 9140840
TI  - Novel missense mutation in cardiac troponin T gene found in Japanese patient with
      hypertrophic cardiomyopathy.
AB  - Familial hypertrophic cardiomyopathy (HCM) is a primary cardiomyopathy with an
      autosomal dominant pattern of inheritance. The disease bearing genes for HCM in
      HCM families have been identified as beta-myosin heavy chain, alpha-tropomyosin,
      cardiac troponin T (cTnT) and myosin binding protein-C genes. In the present
      study, we searched for the mutations in the cTnT gene in Japanese HCM patients.
      Single-strand conformation polymorphism gel analysis of polymerase chain reaction
      amplified product was used to search for the mutations in the exons 8, 9 and 15
      of the cTnT gene from 60 familial HCM patients. Clinical studies of the family
      members were performed and the incidence of sudden or disease-related deaths
      within the family was also examined. We have identified a novel missense mutation
      in exon 9 (Ala104Val) of the cTnT gene in a patient with familial HCM. Because
      the missense mutation was found at the residue conserved through chicken to
      humans and was not detected in the more than 50 normal controls, it was suggested
      that this missense mutation is the cause of HCM in this family. Although the
      affected family members presented moderate hypertrophy of the left ventricular
      wall, they were symptomatic and there was a high incidence of sudden death in her
      family members. Among Japanese patients with familial HCM, a novel missense
      mutation (Ala104Val) in the cTnT gene was identified. Familial HCM is genetically
      heterogeneous in Japanese HCM patients as observed in Caucasian kindreds. The
      disease in the kindred was severe and there was a high incidence of sudden or
      disease-related deaths in the kindred with this mutation.

PMID- 9140841
TI  - KATP channel activation in a rabbit model of chronic myocardial hypoxia.
AB  - Increased tolerance to ischemia exhibited in chronically hypoxia immature rabbit
      hearts is associated with increased activation of ATP-sensitive potassium (KATP)
      channels. We determined whether exposure to hypoxia from birth alters the
      electrophysiological characteristics of Purkinje fibers obtained from rabbits (n
      = 12/group) which were raised in a normoxic (F O2 = 0.21) or hypoxic (F1O2 =
      0.12) environment from birth to 9 days of age and the involvement of the KATP
      channel. The endocardial surface was exposed and impaled with microelectrodes to
      record action potential characteristics from Purkinje fibers under control
      conditions and following exposure to glibenclamide (3 microM). Action potential
      durations (APD)90 in Purkinje fibers were significantly shorter in hypoxic hearts
      compared with normoxic controls (110 +/- 5 ms v 121 +/- 4 ms). Glibenclamide
      increased APD90 in hypoxic hearts (120 +/- 4 ms) to values similar to those
      observed in normoxic controls (121 +/- 4 ms). Glibenclamide had no effect on
      APD90 in normoxic hearts. Maximum diastolic potential was more negative in
      hypoxic hearts and this effect was attenuated by glibenclamide. We conclude that
      chronic myocardial hypoxia results in a shorter APD as compared with normoxic
      controls by enhanced activation of KATP channels.

PMID- 9140842
TI  - Impaired cardioplegic delivery and the loss of cardioprotection: a role for
      preconditioning.
AB  - We have previously shown that, while ischemic preconditioning and cardioplegia
      afford similar protection against injury during ischemia and reperfusion, this
      protection is not additive. However, it is not known whether the same applies
      when the delivery of cardioplegia is suboptimal, such as may occur in the case of
      a coronary stenosis. To investigate the protective effect of cardioplegia v
      preconditioning when the delivery of cardioplegia is impaired, isolated rat
      hearts were subjected to 40 min of global ischemia followed by 40 min of
      reperfusion. Seven groups of hearts (1 g wet wt) were studied (n = 8/group):
      Group 1: controls with unprotected ischemia (no intervention): Group 2: in which
      only 0.2 ml of the St Thomas' cardioplegic solution was administered (2 min)
      prior to ischemia: group 3: in which the volume of cardioplegic solution was
      increased to 0.5 ml: Group 4: received 1.0 ml of cardioplegia: Group 5: received
      2.0 ml of cardioplegia: Group 6: were subjected to ischemic preconditioning (3
      min ischemia, 3 min reperfusion, 5 min ischemia, 5 min reperfusion) prior to
      ischemia: and Group 7: in which ischemic preconditioning and cardioplegia (1.0
      ml) were used in combination. The mean postischemic recovery of left ventricular
      developed pressure (LVDP), expressed as a percentage of its pre-ischemic value,
      was 33 +/- 3% in the control group: this was significantly improved (P < 0.05) in
      hearts receiving 2.0 ml of cardioplegia (59 +/- 5%), whereas volumes of 0.2, 0.5
      or 1.0 ml of cardioplegia afforded no significant protection (recoveries of LVDP
      were 32 +/- 6%, 37 +/- 5% and 37 +/- 5%, respectively). Preconditioning alone and
      the combination of preconditioning plus 1.0 ml of cardioplegia afforded similar
      protection (57 +/- 3%, and 58 +/- 3%, P < 0.05 v controls). At the end of
      reperfusion, left ventricular end-diastolic pressure (LVEDP) was substantially
      increased in control hearts (57 +/- 3 mmHg): it was decreased in the groups
      receiving 2.0 ml of cardioplegic solution (40 +/- 5 mmHg; P < 0.05 v control
      group), but not in the group receiving 0.2, 0.5 or 1.0 ml of cardioplegic
      solution (59 +/- 4, 55 +/- 3 and 54 +/- 4 mmHg, respectively). Again,
      preconditioning alone or preconditioning plus 1.0 ml of cardioplegia afforded
      similar good protection (39 +/- 1 mmHg and 37 +/- 2 mmHg, respectively). A
      similar pattern was observed for the post-ischemic recovery of coronary flow.
      Under conditions where the delivery of cardioplegia is impaired (< 2.0 ml/g
      myocardium) preconditioning alone or preconditioning in combination with
      cardioplegia is more protective that cardioplegia alone. These results may be of
      clinical interest because most patients undergoing surgery for ischemic heart
      disease suffer from severe coronary artery lesions that may prevent the delivery
      of sufficient cardioplegic solution to ensure maximum protection.

PMID- 9140843
TI  - Perceived self-care information needs and information--seeking behaviors before
      and after elective spinal procedures.
AB  - Patients undergoing elective lumbar spinal surgical procedures pose a challenge
      to nurses who provide discharge instruction, because the decreased length of stay
      (LOS) severely limits time for comprehensive discharge instruction. The
      perspectives of 15 adult patients on their perceived self-care information needs
      and information seeking behaviors following elective spinal surgical procedures
      were examined. Content analytic techniques were used to categorize responses.
      Preoperatively, a majority of the subjects (93.3%) indicated that the
      neurosurgeon rather than the nurse, was anticipated to be the sole source of
      information related to self-care needs. Postdischarge, more than half of the
      subjects reported that they had difficulty describing the teaching session
      because they were either too sedated due to the analgesia, or were experiencing
      extreme pain at the time the discharge instruction was being delivered. Results
      substantiate the importance of supplementing oral discharge instruction with
      comprehensive written discharge instruction and of increasing public awareness of
      the teaching expertise of nurses.

PMID- 9140845
TI  - Hope and a health-promoting lifestyle in persons with Parkinson's disease.
AB  - The purpose of this study was to determine relationships between hope and a
      health-promoting lifestyle in adults with varying stages of Parkinson's disease
      (PD) using a descriptive, correlational design. The sample of 42 adults,
      recruited from a PD educational symposium and support groups, completed the Herth
      Hope Index (HHI) and Health-Promoting Lifestyle Profile II (HPLP II). Significant
      correlations were found between hope and a total health-promoting lifestyle and
      spiritual growth and interpersonal relations subscales. Highest subscale means
      were in interpersonal relations and nutrition and the lowest mean was in physical
      activity. Despite a chronic, progressive neurological disease, adults in this
      study perceived themselves as hopeful and engaged in a health promoting
      lifestyle.

PMID- 9140844
TI  - Screening for acute confusion in elderly long-term care residents.
AB  - While acute confusion (AC) is frequently studied in the hospitalized elderly
      population, this phenomena has been largely ignored in elders who are residents
      in long-term care (LTC) facilities. The purpose of this study was to estimate the
      prevalence of AC in older LTC residents, the antecedent conditions present at the
      time of the AC event and the recognition rate of AC when assessed by staff nurses
      in two LTC facilities. This is a descriptive, longitudinal study with a 14 day
      follow-up period which incorporates a screening algorithm using AC instruments
      with established psychometric properties. A behavioral symptom instrument was
      also used in order to classify AC cases into clinical subtypes: hyperkinetic,
      hypokinetic and mixed. Staff nurses, using traditional assessment techniques and
      blinded to the case screening algorithm outcome, were asked to randomly evaluate
      both residents who were "clear" and those experiencing AC. Screening was
      conducted at both daytime and evening time-points. Of the 37 subjects followed.
      15 (40.5%) screened positive for AC. Those AC cases with compromised cortical
      functioning indicative of Alzheimer's disease (n = 4) were particularly
      vulnerable to poor fluid intake. High risk medications (n = 7) and urinary tract
      infections (n = 7) were the most frequent antecedents. Most of the subjects
      experienced two or more antecedent conditions at the time of their AC. Staff
      nurses were able to identify 4 (26.7%) of the 15 instrument-positive residents,
      none of which were of a hypokinetic clinical subtype. These early results suggest
      a high prevalence of AC among elders in LTC, which may go unrecognized by bedside
      care providers.

PMID- 9140846
TI  - Stereotactic radiosurgery for malignant brain tumors: the patient's perspective.
AB  - Stereotactic radiosurgery is a relatively new approach used to treat primary
      malignant brain tumors. Radiosurgery delivers a single-fraction, high dose
      irradiation to a limited target volume of tissue. Stereotactic radiosurgery was
      conceived to be more analogous to conventional surgery than to conventional
      radiotherapy. Eight patients who had primary malignant brain tumors were
      purposefully sampled to participate in this phenomenology study in an effort to
      describe the experience and meaning of the treatment from the patient's
      perspective. Using Colaizzi's phenomenological technique, five potential themes
      emerged from the interviews obtained. They are; (1) A willingness of patients to
      undergo treatment again, (2) self-directed education regarding the treatment
      method, (3) an ability to verbalize the prognosis for their tumor type, (4) the
      lack of discomfort during treatment and (5) the fact that this treatment was not
      originally a treatment option. Additional studies need to be conducted with
      patients undergoing stereotactic radiosurgery for vascular and nonmalignant
      conditions. Implications for nursing practice include an understanding of what
      the experience means to patients. Teaching plans that focus on the patient's
      needs have been developed as a result of this study.

PMID- 9140847
TI  - Soft tissue manipulation: neuromuscular and muscle energy techniques.
AB  - Muscle rigidity and spasms occur with neurological disease and may contribute to
      contractures and shortening of muscle fibers that can interfere with motor
      behaviors, such as ambulation, or activities of daily living, such as combing
      hair, feeding or dressing. The neuromuscular technique (NMT) and muscle energy
      technique (MET) are nursing interventions that can reduce pain and muscle
      rigidity, lengthen muscle fibers and increase range of motion necessary for
      normal motor behavior. Nurses can use these techniques in patients with acute
      neurological diseases and those recovering in rehabilitation and long-term care
      settings. With some neurological diseases, muscle rigidity, increased muscle tone
      and muscle spasms reduce the range of motion of joints and the quality of
      movement. These changes often lead to contractures and impairments in performing
      daily tasks or ambulating, and thus, to loss of independence. Soft tissue
      manipulation can be used to reduce muscle tension and spasms, reduce pain and
      enhance the range of motion of joints whose function depends on the involved
      muscles. Soft tissue manipulation may also improve movement during specific
      tasks. Although the muscle relaxation achieved with manipulation techniques is
      primarily short-term, long-term effects occur. This article describes two
      techniques of soft tissue manipulation, their mechanisms of action, assessment
      and implementation. A case study is used to illustrate application of the
      techniques and possible long-term effects.

PMID- 9140848
TI  - Distinguishing conversion disorder from neurologic impairment.
AB  - Hysteria/conversion disorder has been described since antiquity. One French
      neurologist dubbed it "neurological nonsense" because its presentation was so
      complex and confusing. For nosological purposes for inclusion into the Diagnostic
      Statistical Manual, multiple revisions of conversion disorder terminology were
      made for each edition published from 1952-1994. Until recently, conversion
      disorder was thought to be solely psychological in origin: new studies raise the
      possibility that what is called conversion disorder is actually early disruption
      in the functioning of the nervous system in predisposed individuals. Because of
      its uncanny resemblance to neurological disease, the differential diagnosis is
      critical and should be exhaustive in its efforts to rule out neurological
      disease. The neuroscience nurse needs to be aware of this perplexing syndrome
      called conversion disorder and the never theories that suggest organic causation
      and interventions to enhance recovery.

PMID- 9140849
TI  - Breast cancer in the news: the rise of consumer power in medical care.

PMID- 9140850
TI  - If we ever quizzed our patients.

PMID- 9140851
TI  - The potential impact on women from environmental exposures.

PMID- 9140852
TI  - Prevalence of human immunodeficiency virus infection and drug use in pregnant
      women: a critical review of the literature.
AB  - Many studies have been undertaken in the last 10 years to determine the
      prevalence of both human immunodeficiency virus (HIV) infection and drug use in
      pregnant women. These studies could have a serious impact on the delivery of
      health care as well as the development of health policy. We provide an overview
      of the key findings from these studies and a critical review of their strengths
      and weaknesses. For example, although many prevalence studies were conducted with
      enough participants to reach statistical significance, flaws in study design
      limit the generalizability of the findings. In addition, the development of
      profiles, risk groups, or characteristics was an unsuccessful method of
      identifying pregnant women at risk for drug use or HIV infection. These findings
      have implications for the type of screening procedures that are undertaken in the
      clinical setting and the development of health policy at various levels of
      government. We also conclude that the issue of stigma and discrimination in
      relation to drug and HIV testing, as well as race, gender, and socioeconomic
      status, must be addressed. Finally, we outline how these studies could have a
      significant effect on the health of pregnant women.

PMID- 9140853
TI  - Women's perceptions of their general health, with special reference to their risk
      of coronary artery disease: results of a national telephone survey.
AB  - Previous studies have found that both patients and physicians have misconceptions
      about women's risk of coronary artery disease (CAD). We conducted telephone
      interviews with a representative sample of 1002 American women, focusing on
      women's knowledge of their risk of heart disease, women's preventive health
      behaviors, and what preventive testing is being done by women's physicians.
      Seventy-four percent of all surveyed women rated themselves as fairly or very
      knowledgeable about women's health issues, yet 44% considered themselves somewhat
      or very unlikely to have a heart attack at some point in their lives. Fifty-eight
      percent believed that they were as likely or more likely to die of breast cancer
      than of CAD. Eighty-six percent of the subjects said they see a physician for
      regular checkups, but well over half of this group reported that their physicians
      had never talked to them about heart disease, including 47% of women 45-59 years
      of age and 44% of those > 60. Virtually all women who regularly see a physician
      reported that during routine examinations, they have their blood pressure checked
      (98%) and are weighed (97%), but only 13% reported having their waist and hips
      measured to obtain their waist:hip ratio, and only half reported that their
      doctor recommends cholesterol checks. We conclude that a surprisingly large
      number of women are either not counseled at all or are inadequately counseled
      about their susceptibility to CAD. Furthermore, the quality of the assessment of
      these women for CAD and, presumably, the quality of the treatment they receive
      are subject to question.

PMID- 9140854
TI  - Physician gender and women's preventive services.
AB  - OBJECTIVE: To determine whether the gender of women's regular physicians,
      controlling for physician specialty, is associated with women's receiving key
      preventive services within recommended intervals. DESIGN: Cross-sectional,
      nationally representative women's health telephone survey conducted by Louis
      Harris and Associates in February and March 1993 for The Commonwealth Fund.
      PARTICIPANTS: A total of 2,525 women in the continental United States, > or = 18
      years old, including oversamples of African-American and Hispanic women. MAIN
      OUTCOME MEASURES: Receipt of each of five preventive services (blood pressure
      reading, Pap smear, cholesterol test, clinical breast examination, and mammogram)
      within specific periods. RESULTS: Physician gender makes a significant difference
      for two specialty areas and for three preventive services. Patients of women
      family or general practitioners are more likely than the patients of men to have
      received a Pap smear or a blood cholesterol test within the last 3 years, and the
      patients of women internists are more likely to have received a Pap test.
      Physician gender is associated with a higher likelihood of mammography, but this
      finding was limited to patients ages 40-49 of women family or general
      practitioners. Physician gender does not affect receipt of blood pressure
      screening or breast examination. CONCLUSIONS: Analyses reveal limited evidence
      that physician gender affects women's receipt of preventive services. Physician
      specialty appears to be a more powerful predictor of preventive services
      received. The limited evidence for a physician gender effect, however, is
      relevant for those women who rely on a family or general practitioner or an
      internist for regular care.

PMID- 9140856
TI  - Risk factors associated with women's compliance with estrogen replacement
      therapy.
AB  - An epidemiologic study was carried out in 2106 women 46-63 years of age to
      determine risk factors associated with their compliance or noncompliance with
      estrogen replacement therapy (ERT). Data were obtained from prescription refill
      and medical claims information from centralized prescription and medical claims
      databases of a United Healthcare-affiliated health plan in Minnesota. Study
      participants filled their first ERT prescription during calendar year 1989 or
      1990. Our results indicate that women who are older, use a progestin, experience
      hormone replacement therapy side effects, or see a gynecologist or male physician
      are more likely to be noncompliant. Women who have cardiovascular problems,
      experience menopausal symptoms, or use transdermal estrogen are more likely to be
      compliant. These results suggest that the factors associated with compliance are
      those that indicate that women perceive a benefit from ERT use. The factors
      associated with noncompliance are hormone side effects and gender and specialty
      of the physician prescribing the estrogen.

PMID- 9140855
TI  - Psychological and social factors associated with histories of risk for human
      immunodeficiency virus infection among African-American inner-city women.
AB  - Minority women constitute the fastest-growing segment of the American epidemic of
      human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). The
      present study examined the psychological and social factors related to HIV risk
      among 153 African-American inner-city women who completed measures of HIV risk
      history, sexual and substance use behaviors, perceived risk for HIV infection,
      self-efficacy to reduce risk (belief that one can effectively perform specific
      behaviors), and perceived social norms supporting risk reduction. Fifty-five
      percent of the women (n = 84) reported at least one factor that had placed them
      at known risk for HIV infection. Results of a stepwise regression analysis showed
      that HIV risk history was associated with self-perceived risk for HIV infection
      and self-efficacy to perform risk-reducing actions. Social norms for safer sex
      did not contribute significantly to the explained variance. Women at risk were
      more likely to have been forced or coerced into unwanted sex and were less likely
      to have been familiar with their most recent sex partner. These result suggest
      that HIV risk-reduction interventions targeting inner-city women should focus on
      skills training approaches to build self-efficacy and empower women to adopt risk
      reducing practices.

PMID- 9140858
TI  - Fortifying food with folic acid.

PMID- 9140857
TI  - Participants strengthen clinical trial research: the vital role of participant
      advisors in the Breast Cancer Prevention Trial.
AB  - Views regarding the rights and roles of participants in clinical trial research
      have changed extensively over the past several decades. Such changes have
      included moving from paternalistic views, in which human subjects often were
      totally uninformed of research participation, to a perspective that recognized
      certain rights of human subjects. In recent years, the consumer rights movement,
      a growing customer service perspective in health care, and the growth of a
      variety of advocacy groups have brought further change in attitudes and efforts
      to include consumer representatives and research participants in a variety of
      advisory roles. The BCPT PAB is a model for a way to involve research study
      participants in an expanded role. Members of the board initiate efforts to
      promote participation and inform potential participants about the trial. They
      help establish outreach efforts to recruit individuals from underrepresented
      populations. They serve as effective spokespersons for the trial to the media at
      both local and national levels, and they give highly useful guidance to the NSABP
      and the NCI regarding a variety of aspects of clinical trials. Beyond the formal
      responsibilities that were outlined when the board was established, the trial
      participants serving on the advisory board also have provided inspiration and
      motivation for other participants as well as for the clinicians, researchers, and
      administrators conducting the BCPT. The extensive contributions of the advisory
      board members confirm and add to the understanding of the variety of ways that
      clinical research participants can play a role in strengthening such research
      efforts. Further, the BCPT PAB may serve as a model strategy for drawing on the
      unique resource represented by the participants in clinical trial studies.

PMID- 9140859
TI  - Breast cancer.

PMID- 9140860
TI  - Changes in the haemostatic profile during magnesium deficiency in swine.
AB  - Epidemiological studies of populations living in areas of low magnesium (Mg)
      intake have consistently shown a higher cardiovascular morbidity. Several
      hypotheses have been advanced to explain the cardioprotective properties of
      magnesium. Few studies, however, have analysed the relation of magnesium to
      haemostasis. The overall purpose of this project was to assess the association
      between certain haemostatic variables and magnesium deficiency. This experiment
      was designed to assess the effect of magnesium deficiency on various haemostatic
      variables which may relate to cardiovascular morbidity. Twelve female Yorkshire
      swine were fed for seven weeks on an Mg-sufficient or an Mg-deficient diet. Blood
      samples were obtained at baseline and after the termination of feeding in order
      to evaluate platelet aggregability and concentrations of antithrombin-III (AT
      III), protein C, total protein S, fibronectin, endothelin-1 (ET-1), as well as
      the stable metabolites of thromboxane (TxB2) and prostacyclin (6-keto-PGF1
      alpha). In animals on an Mg-sufficient diet, there were no significant
      differences in any of the investigated haemostatic variables. In the Mg-deficient
      group, a significant decrease in serum magnesium was noted after the feeding
      period (from 2.0 +/- 0.1 to 1.3 +/- 0.1; P < 0.01). Mg-deficient swine showed
      significant increases in ADP-induced (33.3 per cent and 59.6 per cent) and
      collagen-induced (36.6 per cent) platelet aggregation, and decreased plasma
      antithrombin-III (17.7 per cent) and protein S (14.4 per cent) when compared to
      baseline. Plasma concentrations of TxB2 (28.7 per cent), protein C (57.2 per
      cent), and ET-1 (74.9 per cent) were dramatically increased. There were no
      significant differences in plasma fibronectin and 6-keto-PGF1 alpha levels in the
      magnesium-depleted animals. We conclude that magnesium deficiency is associated
      with significant proaggregatory and coagulation alterations. This may contribute
      to the increased cardiovascular morbidity found in magnesium-deficient
      populations. The beneficial effects of magnesium supplementation in an expanding
      array of clinical conditions including cardiovascular disease may, in part, be
      related to the improved haemostatic profile in such patients.

PMID- 9140861
TI  - Epidemiological study of magnesium status and risk of coronary artery disease in
      elderly rural and urban populations of north India.
AB  - Cross-sectional surveys were conducted in 20 randomly selected streets in
      Moradabad city and two villages in Moradabad district in North India to determine
      the association of magnesium with risk of coronary artery disease (CAD). There
      were 501 rural (270 men and 231 women) and 505 urban (250 men and 255 women)
      subjects between 50-54 years of age inclusive. The overall prevalence of CAD was
      three times higher in urban than in rural subjects (11.7 vs. 3.98) and the rates
      were comparable in both sexes. Dietary intake of magnesium was significantly (P <
      0.05) higher in rural subjects in both men (520 +/- 58 vs. 415 +/- 47 mg/d) and
      women (432 +/- 40 vs. 316 +/- 38 mg/d). Dietary magnesium intake and serum
      magnesium were inversely correlated with CAD. The odds ratio for dietary
      magnesium intake indicates a higher prevalence of CAD at lower intakes of
      magnesium in both rural (0.67, 95 per cent confidence interval 0.51 to 0.86) and
      urban (0.72, 95 per cent CI 0.54 to 0.90) subjects. Multivariate regression
      analysis showed that serum and dietary magnesium were significantly associated
      with CAD. Hypertension was not associated with CAD, and serum cholesterol showed
      only weak association in both rural and urban subjects. The inverse association
      of dietary and serum magnesium with CAD shows that some urban populations of
      India may benefit from increased consumption of dietary magnesium and higher
      serum magnesium levels.

PMID- 9140862
TI  - Epidemiological study of magnesium status and risk of hypertension in a rural
      population of north India.
AB  - This cross-sectional survey was conducted in two randomly selected villages in
      Moradabad in North India to demonstrate the association of magnesium status with
      hypertension in relation to socioeconomic status (SES) in a rural population.
      There were 1769 subjects (894 males, 875 females) between 25 and 64 years of age,
      randomly selected and divided into social classes 1-4 depending upon various
      sociological attributes. The survey methods were a validated questionnaire, blood
      pressure measurements by mercury manometer, and blood analysis for serum
      magnesium. Social class 1 and 2 were associated with a greater prevalence of
      hypertension. The overall prevalence of hypertension diagnosed by JNC-V criteria
      (> 140/90 mm Hg) was 17.7 per cent (n = 313) and the prevalence was comparable in
      both sexes and increased with age. Among social class 1 and 2 subjects, there was
      a higher prevalence of obesity and sedentary lifestyle, a lower intake of dietary
      magnesium, and a lower serum magnesium compared to social class 3. Logistic
      regression analysis with adjustment for age showed that SES has a positive
      relation with hypertension (odds ratio 1.08 men, 1.07 women, P < 0.05), body mass
      index (odds ratio 1.14 men, 1.13 women, P < 0.01), and sedentary lifestyle (odds
      ratio 1.38 men, 1.32 women, P < 0.05) in both sexes, and with salt intake in
      women (odds ratio 1.28, P < 0.05). The odds ratio indicated that a higher intake
      of magnesium (odds ratio 1.14 men, 1.17 women, P < 0.05) and a higher serum
      magnesium (odds ratio 1.12 men, 1.15 women, P < 0.05) were associated with a
      lower risk of hypertension. The findings suggest that social class 1 and 2
      subjects in some rural populations of India have a higher prevalence of
      hypertension and dietary intake of magnesium, and serum magnesium levels were
      inversely associated with the risk of hypertension.

PMID- 9140863
TI  - Magnesium determination in clinical diagnosis.

PMID- 9140864
TI  - Interactions between magnesium and vitamin D: possible implications in the immune
      system.
AB  - Evidence clearly shows that magnesium and vitamin D [1 alpha, 25-dihydroxyvitamin
      D3; 1,25(OH)2D3] independently affect numerous aspects of the immune system.
      Although no reports of interactive effects on components of immunity have been
      found, there is evidence that the two nutrients interact in other biosystems,
      sometimes involving calcium. Furthermore, this paper identifies numerous places
      in common where both magnesium and vitamin D reportedly affect immune function.
      Fundamental sites for possible interaction within the immune system include cell
      transformation, regulation of the cell cycle, stabilization of nuclear
      DNA/chromatin, production of reactive oxygen species (ROS), and effects on
      enzymatic and hormonal actions. The presence of different functional, chemical
      forms of both of the nutrients within biological systems, and the availability of
      synthetic drug relatives of both to introduce into such systems, complicate
      interactive studies because such differing forms may not necessarily interact
      similarly or interact at all within the immune system or elsewhere. Regardless,
      there are compelling reasons to believe that examining interactions between
      magnesium and vitamin D within the immune system could prove rewarding,
      especially since the physiological statuses of both nutrients in human
      populations are less than optimum. Such human populations include the elderly
      whose immune function may be compromised.

PMID- 9140866
TI  - A hint on pharmacological and toxicological differences between magnesium
      chloride and magnesium sulphate, or of scallops and men.

PMID- 9140865
TI  - Evidence for magnesium deficiency in the pathogenesis of bronchopulmonary
      dysplasia (BPD).
AB  - Bronchopulmonary dysplasia (BPD) has been defined as a requirement for oxygen for
      more than 28 days because of chronic pulmonary changes, usually in a premature
      infant. About 50 per cent of very low birth weight (VLBW) infants who weigh 1 kg
      at birth and who survive 28 days will develop BPD. Since 80 per cent of fetal
      accretion of magnesium occurs during the third trimester, this population is also
      at risk for magnesium deficiency. This paper reviews evidence for a role of
      magnesium deficiency in the pathogenesis of BPD. Pathology in BPD that may be
      caused or aggravated by magnesium deficiency is noted. Agents or mediators that
      are increased in BPD and in BPD include: oxygen free radicals; the inflammatory
      cytokines interleukin (IL)-1 and IL-6, and tumour necrosis factor-alpha; vaso-
      and bronchoconstrictors thromboxane A2 (TXA2) and serotonin: vasoconstrictor,
      endothelin-1 (ET-1); and bronchoconstrictor, histamine. Magnesium deficiency
      increases the susceptibility of cells and tissues to peroxidation, worsens the
      inflammatory reaction, reduces the immune response, exaggerates catecholamine
      release in stress, and diminishes energy metabolism. Possibly because of the
      danger of magnesium toxicity and the difficulty in studying the preterm VLBW
      neonate, little is known about magnesium supplementation in this group. Such
      information must be gained through controlled studies on the effect of antepartum
      exposure to maternally administered magnesium sulphate on the VLBW infant,
      through carefully monitored postnatal administration of magnesium in an intensive
      care setting, or through evaluations of combined pre- and postnatal
      supplementation.

PMID- 9140867
TI  - Development and evaluation of an inexpensive sensor system for use in measuring
      relative finger positions.
AB  - An inexpensive sensor was developed using a carbon-based electrically conductive
      ink. A correlation of the actual flex angle to the measured flex angle of the
      sensors was obtained by experimentally determining a third-order polynomial that
      represented the response of the sensor and its hardware system (r = 0.999). The
      response time, when going from an angle of 0-90 degrees, was extremely good. The
      sensors exhibited an acceptable dynamic response with an error of less than 5%
      when flexed repeatedly to an angle of 90 degrees. A second-order polynomial was
      found to express the resistance as a function of angle (r = 0.999) for all of the
      sensors tested. Although these sensors are not as precise as the more expensive
      sensors that are available, it was estimated that the production cost of these
      sensors was less then US $0.50 a piece. In addition, there are many ways that the
      sensor production method might be improved to produce more accurate sensors using
      carbon-based electrically conductive ink. While much additional work is still
      necessary, the system presented in this paper could be incorporated into a
      complete device to monitor the rehabilitation of an impaired hand. Unlike other
      systems that are currently available commercially, this system is inexpensive,
      easily manufactured, accurate, and could be readily used in a variety of clinical
      settings.

PMID- 9140868
TI  - An instrument for the non-invasive objective assessment of velar function during
      speech.
AB  - This paper describes the development of a non-invasive, computer-based, clinical
      instrument that infers velar function by way of the measurement of nasal and oral
      airflow. The design criteria of the instrument were based upon a wide ranging
      review of current practice and available techniques. The instrument measures and
      displays both nasal and oral airflow, along with the envelope of the speech sound
      waveform. This allows the clinician to determine whether airflow is associated
      with oral or nasal airflow and, hence, to infer the position of the velum.
      Preliminary clinical trials suggest that the instrument provides valuable
      objective information about the movement of the soft palate, particularly within
      the time domain. Hence, it is believed that the device provides additional
      information for the assessment of velar function, complementing those techniques
      currently employed.

PMID- 9140869
TI  - Parallel principal component neural networks for classification of event-related
      potential waveforms.
AB  - Artificial neural networks (ANNs) are discussed in terms of classification of
      brain auditory event-related potentials (ERPs). A new ANN architecture for the
      classification of ERPs is proposed. The new architecture is called the parallel
      principal component neural network (PPCNN). The use of the PPCNN for
      classification of ERP data obtained from both normal control subjects and chronic
      schizophrenic patients is discussed. Experimental results are given.

PMID- 9140870
TI  - Two artificial neural systems for generation of gait swing by means of
      neuromuscular electrical stimulation.
AB  - A three-layer artificial neural network was used for adaptive control of gait
      swing generated by neuromuscular electrical stimulation (NMES) in a spinal cord
      injured subject. Network inputs consisted of knee and ankle goniometer signals
      for System 1, and knee and hip angular data for System 2. Controller output was
      proportional to changes in applied NMES pulse width (PW). Stimulation was applied
      to the left femoral and common peroneal nerves. The neural networks were trained
      off-line and on-line. Network performance was assessed by applying a number of
      different stimulation PWs and later comparing the resulting motion to a sample
      good step observed during the same test session. On-line training consisted of
      negative and positive reinforcement applied at chosen times. Both on-line and off
      line training algorithms consisted of an enhanced supervised backpropagation
      scheme. Performance evaluation results favour the use of System 1 over System 2.
      Also, a network trained off-line and later submitted to on-line punishment
      appears to be more reliable (in automatic mode) than the same network after it is
      submitted to on-line reward or to off-line training alone. Finally, the systems'
      immediate response to on-line learning was favourable in all cases. Based on the
      results, a version of System 1 was used to generate walking in the test subject.
      This test indicated that the system is promising.

PMID- 9140871
TI  - Analytical study on the kinematic and dynamic behaviors of a knee joint.
AB  - A knee model in the sagittal plane is established in this study. Specifically,
      the model is used to study the effects of inertia, articular surfaces of the knee
      joint, and patella on the behaviors of a knee joint. These behaviors include the
      joint surface contact point, ligament forces, instantaneous center and slide/roll
      ratio between the femur and tibia. Model results are compared to experimental
      cadaver studies available in the literature, as well as between the quasistatic
      and dynamic models. We found that inertia increases the sliding tendency in the
      latter part of flexion, and lengthens the cruciate ligaments. Decreasing the
      curvature of the femur surface geometry tends to reduce the ligament forces and
      moves the contact points towards the anterior positions. The introduction of the
      patellar ligament in the model seems to stabilize the behaviors of the knee joint
      as reflected by the behavior of the instant centers and the contact point pattern
      on the tibia surface. Furthermore, we found that different magnitudes of the
      external load applied to the tibia do not alter the qualitative behaviors of the
      knee joint.

PMID- 9140872
TI  - Force, velocity and energy dynamics of nine load-moving muscles.
AB  - Nine architecturally different muscles of the cat's hindlimb were investigated
      with respect to the kinetic energy, the potential energy, and the force
      variations associated with shortening contractions against gravitational loads.
      Insight about the energy dynamics of contractile muscle can provide a unifying
      concept for models of muscle performance capability. In this study, it was found
      that as contractions shortened from passive equilibrium against a constant mass
      load, acceleration and deceleration phases appeared. These phase were associated
      with muscular force variations of up to 25% of the mass weight in fast twitch
      muscles at low loads. In contrast, slow twitch muscles were associated with less
      than 10% force variations when shortening against a gravitational load. It also
      was found that optimal loads exist which maximize each muscle's ability to impart
      kinetic and potential energy, these optimal loads tend to be in the mid-force
      range for highly pennate muscle and in the low-force range for justform muscles.
      It was concluded that the kinetic energy provided by each muscle is a small
      percentage of that calculated from its length-force relationship, especially at
      low loads. This study confirms that the efficiency of kinetic energy conversion
      is very low at low loads (gradually improving as the loads increase) and thereby
      substantiates early experiments with heat and metabolic energy.

PMID- 9140873
TI  - Comparison between two techniques for modeling interface conditions in a porous
      coated hip endoprosthesis.
AB  - The geometric and material non-linearities occurring at implant interfaces
      require a non-linear foate element analysis to simulate accurately the interface
      conditions. Reviewing the literature, it was found that mainly three different
      non-linear interface elements have been developed to simulate the interface
      bounding conditions. While these different types of interface elements have been
      used to predict micromotions and interface stresses for different geometrical
      configurations and under different loading conditions, no study has attempted to
      compare the performance of these elements under similar conditions. The objective
      of this study is to compare two non-linear interface modeling techniques using
      gap elements and joint/interface elements. A simplified three-dimensional
      geometrical model was developed to compare interface stresses and micromotions
      for both fully and partially coated models. The results show that both non-linear
      modeling techniques predict dissimilar results for the interface stresses in bone
      and prosthesis sides. For the fully coated model, and on the bone side,
      joint/interface elements predict a gradual decrease in stresses from distal end
      to proximal end. However, 'gap' elements predict almost constant stresses in the
      mid-stem region and higher stresses at the distal end. On the prosthesis side,
      small stress differences occur only at the distal and proximal ends. For the
      partially coated model, most significant stress dissimilarities occur in the
      uncoated section. The relative micromotions at the interface were also
      determined. It was found that micromotion patterns obtained using both techniques
      were similar with higher magnitudes in the case of the 'gap' elements.

PMID- 9140874
TI  - Reproducibility of techniques using Archimedes' principle in measuring cancellous
      bone volume.
AB  - Researchers have been interested in developing techniques to accurately and
      reproducibly measure the volume fraction of cancellous bone. Historically bone
      researchers have used Archimedes' principle with water to measure the volume
      fraction of cancellous bone. Preliminary results in our lab suggested that the
      calibrated water technique did not provide reproducible results. Because of this
      difficulty, it was decided to compare the conventional water method to a water
      with surfactant and a helium method using a micropycnometer. The water/surfactant
      and the helium methods were attempts to improve the fluid penetration into the
      small voids present in the cancellous bone structure. In order to compare the
      reproducibility of the new methods with the conventional water method, 16
      cancellous bone specimens were obtained from femoral condyles of human and
      greyhound dog femora. The volume fraction measurements on each specimen were
      repeated three times with all three techniques. The results showed that the
      helium displacement method was more than an order of magnitudes more reproducible
      than the two other water methods (p < 0.05). Statistical analysis also showed
      that the conventional water method produced the lowest reproducibility (p <
      0.05). The data from this study indicate that the helium displacement technique
      is a very useful, rapid and reproducible tool for quantitatively characterizing
      anisotropic porous tissue structures such as cancellous bone.

PMID- 9140875
TI  - Estimation of parameters in a two-pool urea kinetic model for hemodialysis.
AB  - A two-pool, variable volume urea kinetic model for estimation of solute removal
      in hemodialysis is solved analytically, and closed form expressions are presented
      for urea concentration in both compartments, both during dialysis and between
      dialyses. This approach also includes an estimation of the extent of the post
      dialysis rebound phenomenon of urea concentration. A method is presented to
      estimate values for the urea generation rate G, the distribution volume V and its
      partition in two compartments with volumes alpha 1V and alpha 2V (alpha 1-alpha 2
      1), the total clearance K, and intercompartmental transfer coefficient X. To
      apply this analysis, several measurements are needed as input; the urea
      concentration at the end of a dialysis, the evolution of this concentration
      during the next dialysis, with at least four measurements including the initial
      and the final concentration, the volume of the dialysate, and its urea
      concentration. The main results are: the magnitude of the rebound is
      approximately proportional to alpha 2(2) K/X; the accuracy of the parameter
      estimation does not improve much further by taking more than six measurements
      during dialysis.

PMID- 9140876
TI  - Automatic location of vertebrae in digitized videofluoroscopic images of the
      lumbar spine.
AB  - Back pain is a widespread problem, and the disability it engenders continues to
      grow, despite efforts to contain it. A major problem in the diagnosis and
      management of back pain is the assessment of the degree to which mechanical
      factors play a part. Of considerable importance in understanding these mechanical
      factors is being able to quantify how the human spine actually moves in vivo.
      Digitized videofluoroscopy is currently the only practical method available for
      studying spinal motion in vivo at the segmental level. Low-dose, planar motion X
      rays of the spine are captured on videotape and subsequently digitized for
      analysis. Until now, vertebrae in the digitized images were identified and marked
      manually as a basis for calculating intervertebral kinematics. This paper
      describes a procedure for automatically identifying the vertebrae in the motion
      sequences. The process increases objectivity and repeatability, and significantly
      reduces the manual effort required in locating the vertebrae prior to calculating
      the kinematics. The technique has been applied to images of a calibrated model
      and the results are promising. In-plane rotations may be calculated to an
      accuracy of at least 1 degree. Repeated analysis reveals standard deviations of
      less than 0.5 degree for intervertebral rotations and less than 0.25 mm for
      translations.

PMID- 9140877
TI  - Preliminary experience with medical applications of rapid prototyping by
      selective laser sintering.
AB  - Rapid prototyping techniques, originally developed for building components from
      computer aided designs in the motor industry, are now being applied in medicine
      to build models of human anatomy from high resolution multiplanar imaging data
      such a computed tomography (CT). The established technique of stereolithography
      and the more recent selective laser sintering (SLS), both build up an object
      layer by layer. Models have applications in surgical planning, for the design of
      customised implants and for training. Preliminary experience of using the SLS
      technique for medical applications is described, addressing questions regarding
      image processing, data transfer and manufacture. Pilot models, built from nylon,
      included two skills (a child with craniosynoslosis and an adult with
      hypertetorism) and a normal femur which was modelled for use in a bioengineering
      test of an artificial hip. The dimensions of the models were found to be in good
      agreement with the CT data from which they were built-for the child's skull the
      difference between the model and the CT data was less than 1.0 +/- 0.5 mm in each
      direction. Our experience showed that, with care, a combination of existing
      software packages may be used for data conversion. Ideally, image data of high
      spatial resolution should be used. The pilot models generated sufficient clinical
      interest for the technique to be pursued in the orthopaedic field.

PMID- 9140878
TI  - Stress and strain distribution within the intact femur: compression or bending?
      by Taylor et al.

PMID- 9140879
TI  - Can hypotension episodes cause cochlear damage in young subjects?
AB  - In the absence of a satisfactory interpretation, sudden sensorineural hearing
      loss is often attributed either to infective phenomena or to organic-type
      circulatory defects. This latter pathogenesis inevitably comes to mind in elderly
      patients or in the presence of signs of circulatory dysfunction. Nevertheless,
      the not-infrequent observation of sudden hearing loss in young persons lacking
      factors predictive of short-term vascular impairment makes us suppose the
      existence of etiopathogenetic mechanisms of a functional nature. A survey of our
      cases, matched with a control group, revealed the presence of lower mean blood
      pressure levels in the group of young patients with 'idiopathic' sudden hearing
      loss. This finding supports the hypothesis that a condition of haemodynamic
      imbalance linked to hypotension plays a role in the genesis of cochlear damage in
      young subjects. Such a mechanism would bear important therapeutic implications:
      should it be responsible for the damage in at least some cases, vasoactive drugs
      with a vasodilatative action could have adverse effects on the possibility of
      recovery.

PMID- 9140880
TI  - Eating disorders and reflex sympathetic dystrophy syndrome: is there a common
      pathway?
AB  - The comorbidity of eating disorders and reflex sympathetic dystrophy syndrome in
      the same patients raises the possibility of a common pathway for both conditions.
      Reflex sympathetic dystrophy syndrome may be manifesting itself in those
      individuals who have sympathetic overdrive. Microtrauma, often induced by
      compulsive exercise, and depression may be contributory factors. It is
      recommended that: patients with eating disorders who develop pain in an extremity
      should be investigated for possible reflex sympathetic dystrophy syndrome;
      patients with reflex sympathetic dystrophy syndrome should be discouraged from
      dieting, and eating disorders should be suspected if they begin to lose weight or
      are already malnourished.

PMID- 9140881
TI  - Post-spinal hypotension at cesarean section: the denial of evidence.
AB  - Post-spinal hypotension at cesarean section appears difficult to prevent, despite
      the three obligatory so-called preventative measures. So far, literature data
      provide no compelling evidence that expectations have been met in this regard. A
      critical appraisal of volume preload, ephedrine prophylaxis and left lateral
      supine position shows that the preventative measures should be re-evaluated. New
      avenues should be explored aiming at a better prevention and decrease in both the
      prevalence and magnitude of post-spinal hypotension at cesarean section.

PMID- 9140882
TI  - Dissociation as complex adaptation.
AB  - In this article the general theory of complex adaptive systems, substantiated by
      non-linear dynamics, will be used to put the dissociative disorders into a
      theoretical framework and clarify their genesis and presentation. When a system
      is far out of equilibrium, dissipative structures may be formed ('order out of
      chaos', as Prigogine (1) has put it). These structures provide the starting point
      for further evolution and co-evolution of competing groups of functional schemata
      divided on a bifurcation surface. Complex adaptation is almost inevitable in a
      complicated system (such as the brain) driven by non-linear dynamics.
      Dissociation is thus regarded as a consequence of adaptation to a chaotic
      environment rich in contrasts. In a sufficiently complex environment a person
      with dissociative identity disorder is more adapted and thus more likely to occur
      than a 'normal' monopersonality individual.

PMID- 9140883
TI  - Behavioral-neuroendocrine-immunologic interactions in myocardial infarction.
AB  - An enduring state of exhaustion as opposed to chronic hostility-a long-term risk
      factor-has been found to be a more proximal precursor of myocardial infarction.
      The strength of the association with exhaustion suggests that this behavioral
      factor reflects not only a breakdown in adaptation to chronic stressors but also
      the disease process itself. Recent research on the pathogenesis of myocardial
      infarction lends credence to a role for immunological factors. herein, we outline
      a two-stage theoretical model, postulating a feedback relationship between
      behavior, associated neuroendocrine changes, immunological responses, and the
      pathogenesis of this disease. We propose a long-term first stage consisting of
      chronic hostility, prolonged occupational over-exertion, and exposure to other
      life stressors, terminating eventually in a much shorter second stage of 'vital
      exhaustion'. Stressor-associated neuroendocrine changes result in
      immunosuppression leading to reactivation of latent, systemic infections (such as
      cytomegalovirus) and potentially to autoimmune reactions as well. The consequent
      release of pro-inflammatory cytokines exacerbates fatigue and induces a stimulus
      for cytokine production in brain. This cytokine production stimulates a
      chronically activated, over-compensated limbic-hypothalamic-pituitary-adrenal
      axis, resulting in a dampened response, continued exhaustion, and a potential
      'reverberating circuit' between behavior, neuroendocrine change, cytokine release
      and coronary artery occlusion, culminating in myocardial infarction.

PMID- 9140884
TI  - natural antimutagenic agents may prolong efficacy of human immunodeficiency virus
      drug therapy.
AB  - The long-term efficacy of new combination drug therapies for human
      immunodeficiency virus infection may be limited by the tendency of transfected
      human immunodeficiency virus to mutate to drug-resistant forms. This argues for
      the use of safe antimutagenic measures as adjuvants to such therapies. Certain
      nutrients and food factors-notably selenium, green-tea polyphenols, and
      cruciferous phytochemicals-can suppress cancer initiation and mutagenesis in
      animal and cell culture models; epidemiological studies suggest that ambient
      variations in consumption of these food factors can have an important impact on
      human cancer rates. Low-fat diets may reduce deoxyribonucleic acid base damage in
      human leukocytes, whereas increased body iron stores are likely to increase
      mutation rates. Thus, ample but safe intakes of selenium, green-tea polyphenols,
      and cruciferous vegetables, in the context of a diet low in fat and assimilable
      iron, can be expected to prolong the efficacy of drug therapy in subjects
      infected with the human immunodeficiency virus. These measures can also be
      recommended for cancer prevention in the general population.

PMID- 9140885
TI  - A brain model with the circuit to convert short-term memory into long-term
      memory.
AB  - Assuming the existence of encoding synapses which record presynaptic axonal 'on
      off' patterns as the contents of memory, and the existence of modulating synapses
      which help encoding synapses develop long-term potentiation and depression so as
      to convert short-term memory into long-term memory, it is possible to outline a
      brain model according to neuroanatomy. The loop of memory-conversion consists of
      the axons connecting the perceptive cortices, mesotemporal lobes, dorsomedial
      nuclei of thalamus (which also receive axons from septohippocampal complex and,
      indirectly, fornices), and prefrontal lobes. The contents of thought, feeling,
      dreaming, hallucination, and delusion all result from activation of different
      axonal 'on-off' patterns in many sets of synapses, and retrieval of memory,
      reactivation of the presynaptic axonal 'on-off' patterns in the correlating sets
      of synapses. In this model, degenerated synapses may be responsible for the
      thought disorder of schizophrenia.

PMID- 9140886
TI  - Pavlovian conditioning may partly explain the effects of light therapy.
AB  - Explicit pairings of a non-photic stimulus and exposure to light are capable of
      inducing behavioural responses that are characteristic of the resetting of the
      circadian system by light as well as cellular effects in the neural regions that
      are normally activated only by light. The setting of light therapy as used for
      treatment of winter seasonal affective disorder resembles that of Pavlovian
      conditioning. The conditioning may provide a rationale for the sustained
      therapeutic response to light treatment observed to last for the rest of the
      season in some of the patients treated with light.

PMID- 9140887
TI  - Figuring out why we breathe.
AB  - This paper chronicles the evolution of present understanding of cardiopulmonary
      physiology and attempts to illuminate both the thought and innovation of all the
      participating pioneers. Early on, the rate of progress was determined by advances
      in anatomy-the definition of the vascular system and its relationships to the
      heart and lungs. It was held back by concerns, especially religious, with the
      pneuma, and by ignorance of the inability of air and blood to circulate together,
      and of blood's capability to transport gases within its cells. These stumbling
      blocks were set aside successively by the advent of microscopic anatomy (red
      cells and capillaries), chemistry (hemoglobin structure and function; the fact
      that air is a mixture of gases of different properties; processes of combustion;
      and the theory of the conservation of matter), and physics (Bohr effect;
      molecular structure of hemoglobin). Only though access to these facts and
      principles have we been able to approach some inborn errors and to design
      molecular prostheses such as oxygen-carrying microspheres and polyethylene glycol
      hemoglobin.

PMID- 9140888
TI  - Understanding human sexuality--specifically homosexuality and the paraphilias--in
      terms of chaos theory and fetal development.
AB  - This paper considers human sexual orientation, specifically homosexuality and
      some paraphilias, to occur as a result of intrauterine development, itself a
      mathematically chaotic process. Parameter space, an example of state space in the
      phase diagram, has been used to illustrate different phenotypes. The crossing of
      a bifurcation boundary by the developing fetus is proposed as a mechanism by
      which it may be changed from one sexual orientation to another, e.g. from
      heterosexuality to homosexuality. The factors which push the fetus over a
      bifurcation boundary, which include a Y-chromosome, specific hormone
      administration, the lying contiguous to an opposite-sex fetus in multiple
      pregnancies, maternal stress and immune factors are described. The syndromes
      congenital renal hyperplasia and the androgen insensitivity syndrome and their
      relevance to this model are also discussed. Finally, chaos theory is used to
      encompass the complex interactions between fetal development and cultural factors
      in human sexuality.

PMID- 9140889
TI  - Glucosamine may retard atherogenesis by promoting endothelial production of
      heparan sulfate proteoglycans.
AB  - Heparan sulfate proteoglycans produced by vascular endothelium may function
      physiologically to restrain the migration, multiplication, and phenotypic
      transition of vascular smooth-muscle cells, and to maintain an anticoagulant
      luminal surface by bonding and activating antithrombin III. Thus, ample
      production of heparan sulfate proteoglycans may act to prevent atherosclerosis
      and its thrombotic complications. The ability of exogenous heparin to stimulate
      synthesis of heparan sulfate proteoglycans by vascular endothelium may be largely
      responsible for the positive outcomes of most controlled evaluations of low-dose
      heparin as a long-term therapy for coronary disease. Glucosamine, a biosynthetic
      precursor of mucopolysaccharides, can substantially enhance mucopolysaccharide
      production when added to cultured fibroblasts or chondrocytes; the clinical
      utility of oral glucosamine in osteoarthritis may reflect increased synthesis of
      cartilage proteoglycans. It is reasonable to speculate that exogenous glucosamine
      will likewise enhance heparan sulfate proteoglycans production by vascular
      endothelial cells, and, when administered orally in regimens comparable to those
      effective in osteoarthritis, will thereby act to retard atherogenesis.

PMID- 9140891
TI  - Do holes in the T-cell repertoire have a center-surround regulatory structure? A
      rationale for the bifurcation of the Th1 and Th2 pathways of differentiation.
AB  - Regulatory strategies controlling the balance of Th1 versus Th2 T-helper cell
      responses have been a long-standing mystery with important consequences for
      immunological disease. A novel model is presented to explain the comparative
      differentiation of Th1 and Th2 T cells as part of a mechanism to ensure self
      tolerance. This model is based on the assumption that thymic interactions of T
      cell antigen receptors with self major histocompatibility complex ligands may
      vary in efficacy. By this model, fully agonistic major histocompatibility complex
      ligands elicit apoptosis during thymic selection to generate 'holes' in the
      repertoire. Conversely, major histocompatibility complex ligands having some
      degree of partial efficacy (i.e. a mixed agonist/antagonist) may promote Th2
      differentiation whereas fully antagonistic major histocompatibility complex
      ligands elicit Th0 differentiation. Differentiation of Th2 T cells may continue
      in the extrathymic tissues upon continued interactions with self major
      histocompatibility complex ligands having mixed agonist/ antagonist properties.
      By this mechanism, each 'hole' in the repertoire will develop an inhibitory
      surround comprised to Th2 T cell clones having partial reactivities to a
      particular self major histocompatibility complex ligand. During immune responses
      to self-mimicking foreign antigens, the more numerous Th2 T cells of the
      inhibitory surround would prevent clonal expansion and Th1 differentiation of any
      fully autoreactive T cell.

PMID- 9140890
TI  - Superantigens as virulence factors in autoimmunity and immunodeficiency diseases.
AB  - Virulence factors are microbial products that are known to be harmful to the host
      and may assist in the pathogenesis of the micro-organism. Superantigens,
      including those produced by bacteria and viruses, clearly act as virulence
      factors. The clinical effects of superantigens can be not only acute but also
      chronic and complex. Recent evidence suggests that superantigens may play a
      central role in the pathogenesis of autoimmune and immunodeficiency disorders. It
      is our contention that superantigens, as environmental factors, can change a
      controllable disease into one that becomes relentless for susceptible
      individuals. To illustrate the detrimental effects of superantigens on disease
      outcome, modulation of experimental allergic encephalomyelitis by superantigen,
      as well as the potential role of superantigens in human immunodeficiency virus
      pathogenesis will be discussed. The information presented may provide valuable
      insight into the role of superantigens in autoimmunity and human immunodeficiency
      virus infection.

PMID- 9140892
TI  - Attention deficit disorder and hyperactivity--changes in hypothalamic function in
      hyperactive children: a new model.
AB  - This presentation proposes a dynamic integrative model for understanding
      attention deficit disorder and hyperactivity. The proposed model-the lapses model
      is based on principles found in control systems. It suggests the existence of a
      compensatory system employed by the organism in order to correct its internal
      overload and homeostatic disturbances resulting from a hypothalamic dysfunction.
      The restoration of internal homeostasis requires resources needed for the
      interaction with the environment. Allocation of such resources results in lowered
      control ability to the point of total loss of contact with the environment. Thus,
      the compensatory system influences the data-processing ability and determines the
      cognitive style. The limitation of resources directed to coping with the
      surrounding environment, already creates a disturbance at the input level. This
      results in continuity-loss and data-loss due to the temporary saturation and
      oscillations in the arousal level. When balance is regained, the arousal level
      comes back to the optimal range, until such time when accumulated load will again
      cause a disturbance. The cycle repeats itself at varying intervals. The model
      relates to the interaction between three behavioral levels: biochemical-hormonal,
      physiological and cognitive-communicative.

PMID- 9140893
TI  - 1996 J.B. Wolffe Memorial Lecture. Challenging beliefs: ex Africa semper aliquid
      novi.
AB  - The basis of the scientific method is the development of intellectual models, the
      predictions of which are then subjected to scientific evaluation. The more robust
      test of any such model is one that aims to refute or falsify its predictions.
      Successful refutation forces revision of the model: the revised model persists as
      the "truth" until its predictions are, in turn, refuted. Thus, any scientific
      model should persist only as long as it resists refutation. An unusual feature of
      the exercise sciences is that certain core beliefs are based on an historical
      physiological model that, it will be argued, has somehow escaped modern,
      disinterested intellectual scrutiny. This particular model holds that the
      cardiovascular system has a limited capacity to supply oxygen to the active
      muscles, especially during maximal exercise. As a result, skeletal muscle oxygen
      demand outstrips supply causing the development of skeletal muscle hypoxia or
      even anaerobiosis during vigorous exercise. This hypoxia stimulates the onset of
      lactate production at the "anaerobic," "lactate," or ventilation thresholds and
      initiates biochemical processes that terminate maximal exercise. The model
      further predicts that the important effect of training is to increase oxygen
      delivery to and oxygen utilization by the active muscles during exercise. Thus,
      adaptations that reduce skeletal muscle anaerobiosis during exercise explain all
      the physiological, biochemical, and functional changes that develop with
      training. The historical basis for this model is the original research of Nobel
      Laureate A. V. Hill which was interpreted as evidence that oxygen consumption
      "plateaus" during progressive exercise to exhaustion, indicating the development
      of skeletal muscle anaerobiosis. This review confirms that Hill's research failed
      to establish the existence of the "plateau phenomenon" during exercise and argues
      that this core component of the historical model remains unproven. Furthermore,
      definitive evidence that skeletal muscle anaerobiosis develops during submaximal
      exercise at the anaerobic threshold initiating lactate production by muscle and
      its accumulation in blood is not currently available. The finding that exercise
      performance can improve and metabolism alter before there are measurable skeletal
      muscle mitochondrial adaptations could indicate that variables unrelated to
      oxygen use by muscle might explain some, if not all, training-induced changes. To
      accommodate these uncertainties, an alternate physiological model is proposed in
      which skeletal muscle contractile activity is regulated by a series of central,
      predominantly neural, and peripheral, predominantly chemical, regulators that act
      to prevent the development of organ damage or even death during exercise in both
      health and disease and under demanding environmental conditions. During maximal
      exercise, the peripheral regulation of skeletal muscle function and hence of
      oxygen use by skeletal muscle, perhaps by variables related to blood flow, would
      prevent the development of muscle rigor, especially in persons with an impaired
      capacity to produce ATP by mitochondrial or glycolytic pathways. Regulation of
      skeletal muscle contractile function by central mechanisms would prevent the
      development of hypotension and myocardial ischemia during exercise in persons
      with heart failure, of hyperthermia during exercise in the heat, and of cerebral
      hypoxia during exercise at extreme altitude. The challenge for future generations
      of exercise physiologists is to identify how the body anticipates the possibility
      of organ damage and evokes the appropriate control mechanism(s) at the
      appropriate instant.

PMID- 9140894
TI  - Maximal oxygen uptake: "classical" versus "contemporary" viewpoints.
AB  - The traditional view of VO2max owes a great deal to the work of A. V. Hill, who
      conducted experiments on exercising man in Manchester, England, in the 1920's.
      Hill and colleagues proposed that there is an upper limit to oxygen uptake
      (VO2max), that there are inter-individual differences in this variable, and that
      VO2max is limited by the circulatory and/or respiratory systems. They
      demonstrated that oxygen uptake increases linearly with running speed, but in
      some subjects it eventually "reaches a maximum beyond which no effort can drive
      it," a phenomenon now referred to as the VO2 plateau. In recent years, Timothy
      Noakes has strongly criticized Hill's concept of VO2max. He maintains that the
      absence of a VO2 plateau in some subjects is proof that oxygen delivery is not a
      limiting factor for VO2max. This view fails to recognize that the plateau is not
      the principal evidence for a cardiorespiratory limitation. Noakes rejects the
      VO2max paradigm of A. V. Hill in its entirety. The alternative paradigm he
      proposes is that endurance performance is limited by "muscle factors." Noakes
      suggests that the best distance runners have muscle characteristics that allow
      them to achieve higher running speeds, and since running speed is linearly
      related to oxygen uptake, an indirect consequence of this is that they will have
      higher VO2max values. This is exactly the opposite of how the relationship
      between VO2max and running speed at the end of a maximal exercise test should be
      viewed. Noakes offers little evidence to support his views, and they conflict
      with a vast body of scientific evidence showing that oxygen transport is a major
      determinant of endurance performance. After carefully reviewing the evidence on
      both sides of the issue, we conclude that the older "classical" VO2max paradigm
      of A. V. Hill is the correct one.

PMID- 9140895
TI  - Effect of a rhinovirus-caused upper respiratory illness on pulmonary function
      test and exercise responses.
AB  - Upper respiratory illness (URI) may cause more frequent acute disability among
      athletes than all other diseases combined. The purposes of this study were to
      determine the impact of a rhinovirus-caused URI on resting pulmonary function
      submaximal exercise responses and on maximal exercise functional capacity. Twenty
      four men and 21 women (18-29 yr) of varying fitness levels were assigned to the
      experimental group (URI), and 10 additional individuals served as a control group
      (CRL). An initial serological screening was performed on all URI group subjects
      to exclude those with the rhinovirus 16 (HRV16) antibody. All subjects completed
      both a baseline pulmonary function test and a graded exercise test to volitional
      fatigue. URI subjects were inoculated with HRV 16 on two consecutive days within
      10 d of completing these tests. The day following the second inoculation (peak of
      illness), post-inoculation pulmonary function and graded exercise tests were
      performed. A noninfected control group completed these same pulmonary and
      exercise tests 1 wk apart. ANOVA identified no significant differences (P < 0.05)
      at minutes 2, 5, and 8 for the physiological responses measured between the pre-
      and post-exercise tests for both the URI and CRL, groups. Furthermore, there were
      no significant differences between maximal exercise performance between running
      trials for either group. There was also no significant interaction between
      treatment (pre/post URI) and group for any of the pulmonary function measures
      obtained. In conclusion, physiological responses to pulmonary function testing
      and submaximal and maximal exercise do not appear to be altered by an URI.

PMID- 9140896
TI  - Failure of manual massage to alter limb blood flow: measures by Doppler
      ultrasound.
AB  - The ability of manual massage to alter muscle blood flow through three types of
      massage treatments in a small (forearm) and a large (quadriceps) muscle mass was
      tested in 10 healthy individuals. A certified massage therapist administered
      effleurage, petrissage, and tapotement treatments to the forearm flexors (small
      muscle mass) and quadriceps (large muscle mass) muscle groups in a
      counterbalanced manner. Limb blood flow was determined from mean blood velocity
      (MBV) (pulsed Doppler) and vessel diameter (echo Doppler). MBV values were
      obtained from the continuous data sets prior to treatment, and at 5, 10, and 20 s
      and 5 min following the onset of massage. Arterial diameters were measured
      immediately prior to and following the massage treatments; these values were not
      different and were averaged for the blood flow calculations. The MBV (e.g., 5.77
      +/- 0.4 and 9.73 +/- 0.7 cm.s-1) and blood flows (39.1 +/- 6.4 and 371 +/- 30
      ml.min-1) for brachial and femoral arteries, respectively, were not altered by
      any of the massage treatments in either the forearm or quadriceps muscle groups
      (P > 0.05). Mild voluntary handgrip (approximately 35% maximal voluntary
      isometric contraction) and knee extension (15 cm) contractions resulted in peak
      blood velocities (15.2 +/- 1.2 and 28.1 +/- 3.1 cm.s-1) and blood flow (126 +/-
      19 and 1087 +/- 144 ml.min-1) for brachial and femoral arteries, respectively,
      which were significantly elevated from rest (P < 0.05). The results indicate that
      manual massage does not elevate muscle blood flow irrespective of massage type or
      the muscle mass receiving the treatment. Further, the results indicate that if an
      elevated muscle blood flow is the desired therapeutic effect, then light exercise
      would be beneficial whereas massage would not.

PMID- 9140898
TI  - Plasma glucose metabolism during exercise: effect of endurance training in
      humans.
AB  - It has long been recognized that endurance training reduces the reliance on
      carbohydrate as a source of energy during submaximal exercise. Historically, this
      has been ascribed to a decrease in muscle glycogen utilization. However, recent
      studies have demonstrated that, at least in humans, training also reduces the
      production and utilization of plasma-borne glucose during exercise. The latter is
      true not only during moderate exercise performed at the same absolute intensity
      before and after training, but also during intense exercise performed at the same
      relative intensity in the trained and untrained states. Moreover, this adaptation
      is often quantitatively just as important as the decline in muscle glycogen
      utilization in accounting for the overall carbohydrate-sparing effect of
      training. This reduced reliance on plasma glucose, which appears to result from a
      decrease in muscle glucose transport, seems to be related to the training-induced
      increase in muscle mitochondrial respiratory capacity. On the other hand the
      training-induced decrease in glucose production (which is the result of
      reductions in both hepatic glycogenolysis and gluconeogenesis) is probably
      largely due to alterations in the glucoregulatory hormone response to exercise,
      although other factors (such as changes in hepatic hormone sensitivity and/or
      responsiveness) may also play a role. By minimizing the possibility of
      hypoglycemia, these adaptations in glucose production and utilization likely
      contribute to the increased endurance that results from exercise training.

PMID- 9140897
TI  - Exposure to anabolic-androgenic steroids shortens life span of male mice.
AB  - Adult male laboratory mice were exposed for 6 months to a combination of four
      anabolic-androgenic steroids of the kinds and at the relative levels to which
      human athletes and body builders expose themselves. The four steroids included
      testosterone, two 17-alkylated steroids, and an ester, and they were given at
      doses that totaled either 5 or 20 times normal androgenic maintenance levels for
      mice. By the time the survivors were 20 months old (1 yr after the termination of
      steroid exposure), 52% of the mice given the high dose of steroids had died
      compared with 35% of the mice given the low dose and only 12% of the control mice
      given no exogenous hormones (P < 0.001). Autopsy of the steroid-treated mice
      typically revealed tumors in the liver or kidney, other kinds of damage to these
      two organs, broadly invase lymphosarcomas, or heart damage, and usually more than
      one of these conditions. It can be concluded that the life span of male mice is
      decreased dramatically by exposing them for 6 months to the kinds and relative
      levels of anabolic steroids used by many athletes and body builders.

PMID- 9140899
TI  - Training enhanced hepatic gluconeogenesis: the importance for glucose homeostasis
      during exercise.
AB  - Endurance training has long been known to improve the individual's resistance to
      exercise-induced hypoglycemia. Traditionally attributed to a reduction in glucose
      uptake subsequent to enhanced fat oxidation, this issue has only recently been
      directly addressed. This paper briefly reviews the evidence for reduced glucose
      uptake versus enhanced glucose production in the improved hypoglycemic resistance
      following training. While whole body glucose removal and production may be
      reduced following training, this has only been demonstrated under exercising
      conditions in which glycemia demonstrates little deviation from rest. Under
      exercise conditions where untrained animals demonstrate substantial reductions in
      blood glucose, training enhanced hypoglycemic resistance has been shown to result
      entirely from enhanced glucose production via gluconeogenesis. Using the in situ
      perfused liver preparation, the authors have provided direct evidence for a
      training enhanced hepatic gluconeogenic capacity. The site of adaptation within
      the gluconeogenic pathway has now been constrained to below the level of the
      triose phosphates. Lack of evidence for suppressed skeletal muscle glucose uptake
      following training, a uniform observation for humans and rats, is also discussed.
      It is concluded that the improved hepatic gluconeogenic capacity of endurance
      trained individuals, at least in rats, is critical to their demonstrated
      resistance to exercise-induced hypoglycemia.

PMID- 9140900
TI  - Effect of endurance training on fatty acid metabolism during whole body exercise.
AB  - Endurance exercise training increases fat oxidation during large muscle mass
      exercise. Although the source of this fat has been thought to be plasma free
      fatty acids (FFA) released from adipose tissue, the training-induced decrease in
      lipolytic hormonal responses to exercise is not consistent with this concept. The
      purpose of this communication is to review findings, from our laboratory
      indicating that, in young healthy subjects, endurance exercise training reduces
      plasma FFA turnover and oxidation during moderate intensity prolonged 2-leg
      cycling while simultaneously enhancing depletion of triglycerides from the active
      musculature. Evidence is presented that metabolism of intramuscular triglycerides
      can explain the increase in total fat oxidation observed in the trained state
      during large muscle mass exercise. However, these results may not be applicable
      to exercise involving small muscle groups, a distinction that is likely to be
      important in explaining the apparent conflict between our findings and those from
      other laboratories where experimental conditions were different. In summary, for
      large muscle mass exercise up to 2 h in duration, plasma FFA are a less important
      fuel source in the trained state, and intramuscular triglycerides supply the
      major portion of the increase in oxidized fatty acids.

PMID- 9140901
TI  - Effect of endurance training on fatty acid metabolism: local adaptations.
AB  - Older studies of humans seem to suggest a correlation between free fatty acid
      (FFA) turnover and oxidation on the one hand and plasma FFA concentration on the
      other hand during submaximal exercise. However, recent studies, in which higher
      concentrations of plasma FFA have been reached during prolonged submaximal
      exercise, have revealed a levelling off in net uptake in spite of increasing
      plasma FFA concentrations. Furthermore, this relationship between FFA
      concentration and FFA uptake and oxidation is altered by endurance training.
      These recent findings in humans support the notion from other cell types that
      transmembrane fatty acid transport is not only by simple diffusion, but
      predominantly carrier-mediated. During prolonged submaximal knee-extension
      exercise it has been demonstrated that the total oxidation of fatty acids was
      approximately 60% higher in trained subjects than in nontrained subjects. The
      training-induced adaptations responsible for this increased utilization of plasma
      fatty acids by the muscle could be located at several steps from the mobilization
      of fatty acids to skeletal muscle metabolism in the mitochondria. In this paper
      regulation at the transport steps and also at various metabolic steps is
      discussed.

PMID- 9140902
TI  - Effect of endurance training on ammonia and amino acid metabolism in humans.
AB  - Few studies examine ammonia and amino acid metabolism in response to endurance
      training. Trained humans generally experience less increase in plasma ammonia
      during either prolonged or intense exercise. This is probably a reflection of
      reduced ammonia production and release from the active muscle; it could be a
      reflection of decreased AMP deaminase activity, decreased glutamate dehydrogenase
      activity, and/or increased alanine and glutamine formation. Little is known
      regarding the associated enzyme systems in humans, but in experiments with animal
      models, aerobic training decreases AMP deaminase and increases the enzymes of
      amino acid transamination and oxidation.

PMID- 9140904
TI  - Aldosterone and vasopressin responses in the heat: hydration level and exercise
      intensity effects.
AB  - We examined the separate and combined effects of hypohydration level and exercise
      intensity on aldosterone (ALD) and arginine vasopressin (AVP) responses during
      exercise-heat stress. Nine heat acclimated men performed 50 min of treadmill
      exercise in a warm room (30 degrees C dry bulb (DB), 50% relative humidity (RH)
      at 25%, 45% and 65% VO2max when euhydrated and when hypohydrated by 3% and 5% of
      body weight. Blood samples were drawn at rest and at 20 min of exercise. ALD and
      AVP increased (P < 0.05) in a graded manner with hypohydration level, and this
      effect persisted during exercise-heat stress. High intensity exercise produced
      greater ALD and AVP increases than low intensity exercise. ALD responses during
      exercise were independent of hypohydration level. AVP responses were closely
      related to osmolality (N = 6 of 7 subjects; r = 0.51 to r = 0.98; average r =
      0.84) despite varying hydration, exercise intensity, or core temperature. We
      conclude that: 1) ALD and AVP increase in a graded manner with hypohydration, and
      this effect persists during exercise-heat stress; 2) ALD and AVP increases
      elicited by exercise are greater during high intensity than low intensity
      exercise; 3) Hypohydration and exercise intensity have additive effects on ALD:
      and 4) AVP responses are closely coupled to osmolality.

PMID- 9140903
TI  - Lactate distribution in the blood during progressive exercise.
AB  - The purpose of this study was to examine the effect of increment durations of 1
      min and 4-min during progressive incremental exercise tests on: 1) the
      distribution of lactate between plasma and red blood cells (RBCs), and 2) lactate
      threshold (LT) detection via three conventional methods using whole blood lactate
      concentration ([La]) or plasma [La]. Eight males (age, 22.5 +/- 0.6 yr: height,
      170.6 +/- 2.3 cm, weight, 76.0 +/- 3.1 kg, and VO2peak, 42.8 +/- 2.0 mL.kg-1.min
      1) performed two progressive load tests to volitional fatigue on a cycle
      ergometer. Work rate was increased 30 W at 1-min or 4-min intervals. All data
      were normalized to individual LT work rates. For both protocols, whole blood
      [La], plasma [La], RBC [La], and [La] gradient increased significantly (P < 0.05)
      after exercise intensity exceeded LT. However, the RBC:plasma [La] ratio remained
      at the resting value throughout the progressive exercise tests. The increase in
      [La] gradient after LT, with no change in the RBC:plasma lactate ratio, suggests
      that given an incremental work rate increase of 30 W, 1 min is adequate for
      equilibration of lactate between the plasma and RBCs. Also, under the conditions
      of this investigation, neither blood fraction analyzed nor exercise protocol had
      any effect on estimations of LT (in terms of VO2) by the Visual and Log-Log
      methods. However, LT determined by a fixed [La] of 2 mM may underestimate LT when
      plasma samples are used.

PMID- 9140906
TI  - Interpreting the relation between force and cross-sectional area in human muscle.
AB  - The maximum force a muscle can produce depends on its cross-sectional area (CSA).
      However, the exact interpretation of this relationship has been a matter of
      controversy. Recently, the controversy has centered on whether the measurements
      are best correlated using regression analysis or ratio standards. Applying
      regression analysis to this problem implies that all the experimental error is in
      the measurement of force. Thus, confusion may arise by failure to take account of
      errors in the measurement of CSA. Using a statistical model, we show how
      regression analysis can be misleading as error is introduced into the measurement
      of CSA as well as that of force. Because neither the errors in force nor CSA can
      be quantified in the experimental situation, we conclude that ratio standards are
      less likely to mislead although the accuracy of the result depends on the degree
      of correlation between force and CSA in the muscle measured.

PMID- 9140905
TI  - Exercise training decreases the growth hormone (GH) response to acute constant
      load exercise.
AB  - To assess the influence of exercise training on the growth hormone (GH) response
      to acute exercise, six untrained males completed a 20-min, high-intensity,
      constant-load exercise test prior to and after 3 and 6 wk of training (the
      absolute power output (PO) during each test remained constant x PO = 182.5 +/-
      29.5 W). Training increased (pre- vs post-training) oxygen uptake (VO2) at
      lactate threshold (1.57 +/- 0.33 L.min-1 vs 1.97 +/- 0.24 L.min-1 P < or = 0.05).
      VO2 at 2.5 mM blood lactate concentration ([HLa]) (1.83 +/- 0.38 L.min-1 vs 2.33
      +/- 0.38 L.min-1, P < or = 0.05), and VO2peak (3.15 +/- 0.54 L.min-1 vs 3.41 +/-
      0.47 L.min-1, P < or = 0.05). Power output at the lactate threshold (PO-LT)
      increased with training from 103 +/- 28 to 132 +/- 23W (P < or = 0.05).
      Integrated GH concentration (20 min exercise + 45 min recovery) (microgram.L-1 x
      min) after 3 wk (138 +/- 106) and 6 wk (130 +/- 145) were significantly lower (P
      < or = 0.05) than pre-training (238 +/- 145). Plasma epinephrine and
      norepinephrine responses to training were similar to the GH response (EPI-pre
      training = 2447 +/- 1110; week 3 = 1046 +/- 144; week 6 = 955 +/- 322 pmol.L-1; P
      < or = 0.05; NE pre-training = 23.0 +/- 5.2; week 3 = 13.4 +/- 4.8; week 6 = 12.1
      +/- 6.8 nmol.L-1; P < or = 0.05). These data indicate that the GH and
      catecholamine response to a constant-load exercise stimulus are reduced within
      the first 3 wk of exercise training and support the hypothesis that a critical
      threshold of exercise intensity must be reached to stimulate GH release.

PMID- 9140907
TI  - Effects of steady-state versus stochastic exercise on subsequent cycling
      performance.
AB  - The aims of this investigation were to evaluate the physiological responses to
      laboratory based stochastic exercise and to assess the effects of stochastic
      versus steady-state exercise on subsequent cycling time trial (TT) performance.
      Six competitive cyclists (peak power output (PPO) 432 +/- 39 W (values are mean
      +/- SD) undertook in a random order two 150-min paced rides that were either
      constant load (58% of PPO) or stochastic in nature (58 +/- 12.2% of PPO). These
      rides were immediately followed by a 20-km TT performance on an air-braked
      ergometer. Mean heart rate (HR) responses throughout the 150-min paced rides and
      during the subsequent TT were not significantly different between trials. Yet,
      despite the similarities in HR, the mean time for the TT was significantly faster
      (26:32 +/- 1:30 vs 28:08 +/- 1:47 min, P < 0.05) and the mean power output was
      significantly greater (340.3 +/- 44.2 vs 302.5 +/- 42.3 W; 77.8 +/- 10.2 vs 70.0
      +/- 9.8% of PPO, P < 0.05) following the steady-state ride. These results
      demonstrate that following 150 min of steady-state riding, subsequent 20 km TT
      performance was significantly improved when compared with 150 min of stochastic
      exercise.

PMID- 9140908
TI  - Effects of training volume on sleep, psychological, and selected physiological
      profiles of elite female swimmers.
AB  - Excessive training is reported to cause sleep disturbances and mood changes. We
      examined sleep and psychological changes in female swimmers across a competitive
      swimming season, that is, at the start of the season (onset), during peak
      training period (peak), and after a precompetition reduction in training (taper).
      For each phase, polysomnographic recordings, body composition, psychological
      parameters, and swimming performance were obtained. A daily training log and
      sleep diary were maintained for the entire study period. Sleep onset latency
      (SOL) time awake after sleep onset, total sleep time (TST), and rapid eye
      movement (REM) sleep times were similar at all three training levels. Slow wave
      sleep (SWS) formed a very high percentage of total sleep in the onset (26%) and
      peak (31%) training periods, but was significantly reduced following
      precompetition taper (16%), supporting the theory that the need for restorative
      SWS is reduced with reduced physical demand. The number of movements during sleep
      was significantly higher at the higher training volumes, suggesting some sleep
      disruption. In contrast to other studies, mood deteriorated with a reduction in
      training volume and/or impending competition.

PMID- 9140909
TI  - Effect of 4 wk of deep water run training on running performance.
AB  - The purpose of this study was to determine whether trained competitive runners
      could maintain on-land running performance using 4 wk of deep water run training
      instead of on-land training. Eleven well-trained competitive runners (10 males, 1
      female; ages, 32.5 +/- 5.4 yr; height, 179.8 +/- 9.3 cm; weight, 70.4 +/- 6.7 kg
      (mean +/- SD)) trained exclusively using deep water run training for 4 wk.
      Subjects trained 5-6 d.wk-1 for a total of 20-24 sessions (mean +/- SD, 22 +/-
      1.5 sessions). Instruction and practice sessions were conducted prior to the
      training period. Before and after the deep water run training, subjects completed
      a 5-km race on the treadmill using a computer based system, a submaximal run at
      the same absolute workload to assess running economy, and a combined lactate
      threshold and maximal oxygen consumption test. No significant differences were
      found for (mean +/- SEM): 5-km run time (pre, 1142.7 +/- 39.5 s; post, 1149.8 +/-
      36.9 s; P = 0.28), submaximal oxygen consumption (pre 44.8 +/- 1.2 mL.kg-1.min-1;
      post, 45.3 +/- 1.5 mL.kg-1.min-1; P = 0.47), lactate threshold running velocity
      (pre, 249.1 +/- 0.9 m.min-1; post, 253.6 +/- 6.3 m.min-1; P = 0.44), or maximal
      oxygen consumption (pre, 63.4 +/- 1.3 mL.kg-1.min-1; post, 62.2 +/- 1.3 mL.kg
      1.min-1; P = 0.11). Also no differences were found among Global Mood State pre
      training, each week during training, and post-training. Competitive distance
      runners maintained running performance using 4 wk of deep water run training as a
      replacement for on-land training.

PMID- 9140910
TI  - Comparison of methods for evaluating exercise-induced changes in thromboxane B2
      and beta-thromboglobulin.
AB  - This study compared the effects of exercise or TXB2 and beta-TG when evaluated by
      four methods: 1) not adjusted; 2) adjusted for plasma volume changes (PV); 3)
      standardized per 10(5) platelets (PC); 4) or both PC and PV (PC-PV). Blood was
      collected from 16 men (41.3 +/- 8.1 yr) at rest after 30 min of exercise (IPE)
      and after 30 min recovery. Resting TXB2 and beta-TG concentrations were 62.0 +/-
      6.2 pg.mL-1 and 129.8 +/- 12.5 ng.mL-1, respectively. When expressed on a per
      10(5) platelet basis, resting PCTXB2 was 23.8 +/- 2.8 pg.mL-1.10(5-1) platelets
      and PC beta-TG was 50.77 +/- 6.0 ng.mL-1. 10(5-1) platelets. At IPE, TXB2
      decreased 20.5% and beta-TG increased 13.6%. Thirty minutes after exercise TXB2
      was 4.2% lower than resting values, whereas beta-TG was 26% higher. TXB2, beta
      TG, PVTXB2, and PV beta-TG were not significantly altered by exercise. The only
      significant changes in TXB2 occurred at IPE when values were adjusted for changes
      in platelet count. At IPE, PCTXB2, and PC-PVTXB2 decreased 32.8% and 33.6%,
      respectively (P < 0.05). Similarly, beta-TG were not altered significantly by
      exercise except when the samples taken after 30 min of recovery were adjusted for
      changes in platelet count. At 30 min post-exercise PC beta-TG and PC-PV beta-TG
      were 21.2% and 28.4% greater (P < 0.05) than the resting beta-TG values. These
      data suggest that methods used to adjust concentrations of platelet derived
      substances for changes owing to exercise may influence conclusions about the
      effect of exercise on platelet function. Thus, it is imperative that researchers
      consider the purpose for which they are collecting TXB2 and beta-TG, as well as
      other constituents derived from blood cells, before they determine which methods
      of analysis to use.

PMID- 9140911
TI  - Assessing body composition before and after resistance or endurance training.
AB  - This study's purpose was to determine the validity of near-infrared interactance
      (NIR) and bioelectric impedance (BIA) in tracking changes in body composition
      over 12 wk of either a high intensity endurance (ET) or resistance (RT) training
      program in nondieting weight-stable untrained males. Prior to and following the
      control or training period, each subject completed a series of body composition
      analyses including hydrostatic weighing (HW) with a measurement of residual
      volume: anthropometric measurements including height, weight, skinfold, and
      girth: BIA measurement: and NIR measurements. Based on the HW results, there were
      no significant body composition changes in the control group. For the ET group, a
      significant decline in relative body fat resulted from a reduction in fat weight
      (FW) with no change in fat-free weight (FFW). In the RT group, both a significant
      decline in FW and an increase in FFW contributed to this group's decline in
      relative body fat. Tracking changes in relative body fat, FW, and FFW, skinfolds
      agree reasonably well with HW in all groups while BIA and NIR did not always
      track body composition changes well. For example, SF and BIA were significantly
      correlated with the changes in FFW (HW = +4.1%, SF = +4.5%. BIA = +3.1%. NIR = 
      0.7%) observed in the RT group compared to HW (SF: r-value = 0.45, SEE = 2.5;
      BIA: r = 0.33, SEE = 3.4) while the NIR measurements were nonsignificant (r =
      0.09, SEE = 5.0). Interestingly, NIR underestimated the gain in FFW in the
      resistance trained group while BIA underestimated the changes in relative body
      fat. FW, and FFW in the endurance trained group. Based on these results, BIA and
      NIR appear not to be appropriate measurement tools for tracking body composition
      changes in endurance and resistance training individuals respectively.

PMID- 9140912
TI  - Normalizing strength for body size differences in older adults.
AB  - The purpose of this study was to compare the normalization methods of ratio
      standards, allometry, and ANCOVA with knee extensor strength of older adults. The
      apparently healthy older volunteers were 71 men (mean +/- SD; age, 71 +/- 4 yr;
      body mass, 81 +/- 10 kg; height, 174 +/- 7 cm) and 77 women (71 +/- 4 yr, 65 +/-
      8 kg, 160 +/- 5 cm. respectively). Strength was defined as peak torque (N.m-1)
      and measured with a Cybex II isokinetic dynamometer. Body composition was
      estimated with dual energy x-ray absorptiometry. With allometry, the body mass
      exponent (0.74) was not statistically different from theory (0.67). Body mass
      adjusted strengths were 34.7% (allometry), 32.0% (ANCOVA), and 29.4% (ratio
      standards) greater in older men than women. Allometry revealed that the bone-free
      lean tissue mass exponent was not different from ratio standard exponent of 1.0.
      After adjustment by bone-free lean tissue mass, strength in men remained 16.0%
      (allometry and ratio standards) higher than in women, but, strength differences
      between genders were eliminated with ANCOVA. The methods used to normalize
      strength yielded similar results with body mass but conflicting results with bone
      free lean tissue mass.

PMID- 9140913
TI  - American College of Sports Medicine position stand. The Female Athlete Triad.
AB  - The Female Athlete Triad is a syndrome occurring in physically active girls and
      women. Its interrelated components are disordered eating, amenorrhea, and
      osteoporosis. Pressure placed on young women to achieve or maintain
      unrealistically low body weight underlies development of the Triad. Adolescents
      and women training in sports in which low body weight is emphasized for athletic
      activity or appearance are at greatest risk. Girls and women with one component
      of the Triad should be screened for the others. Alone or in combination, Female
      Athlete Triad disorders can decrease physical performance and cause morbidity and
      mortality. More research is needed on its causes, prevalence, treatment, and
      consequences. All individuals working with physically active girls and women
      should be educated about the Female Athlete Triad and develop plans to prevent,
      recognize, treat, and reduce its risks.

PMID- 9140914
TI  - Expression of the green fluorescent protein (GFP) in mycobacterium avium as a
      tool to study the interaction between Mycobacteria and host cells.
AB  - Mycobacterium avium is an intracellular pathogen able to invade and survive
      within macrophages and mucosal epithelial cells. The study of the interaction
      between M. avium and host cells is important to establish the mechanisms of
      pathogenesis of the infection. One of the limitations of microscopic study of
      intracellular M. avium is the difficulty of identifying isolated bacilli within
      cells. As a general strategy to visualize and analyse the influence of M. avium
      on intracellular trafficking, we cloned the gene encoding the green fluorescent
      protein (GFP) in M. avium. A vector was constructed by cloning the cDNA for the
      GFP of the bioluminescent jellyfish Aequorea victoria into an Escherichia
      coli/Mycobacteria shuttle vector (pMV261). The recombinant plasmid (pWES-4) was
      transformed into both E. coli and M. avium strain 104 (serovar 1). The
      transformants were screened for strong expression of the GFP. Transformed M.
      avium were clearly visible inside human macrophages and epithelial cells using
      fluorescence microscopy. These transformed M. avium should provide a useful tool
      for further study of intracellular behaviour.

PMID- 9140915
TI  - A search for cholera toxin (CT), toxin coregulated pilus (TCP), the regulatory
      element ToxR and other virulence factors in non-01/non-0139 Vibrio cholerae.
AB  - Twenty-four selected non-O1/non-O139 Vibrio cholerae strains were examined for
      the presence of virulence associated genes like ctxA, tcpA, toxR and the
      repetitive sequence (RS element). Seventeen of these were isolated from
      diarrhoeal stool samples while the remaining seven were of local environmental
      origin. Nine and four respectively of these strains were positive for ctxA and
      tcpA by Multiplex PCR analysis. The majority (16 out of 18 tested) of the strains
      (including the four tcpA + strains) contained toxR sequences as determined by
      another PCR assay. The presence of RS element was demonstrable in ctxA+ strains
      only. Interestingly, three of these non-O1/non-O139 strains were shown to contain
      all the three virulence associated genes (ctxA, tcpA and toxR) as well as the RS
      element. Two of these belonged to serogroups 037 (V2) and 064 (CG15) while the
      third one (V315-1) was untypable. These three strains also produced cholera
      toxin, expressed toxin coregulated pilus (TCP) and/or TcpA related antigens when
      grown under appropriate culture conditions. Southern hybridization analysis of
      their chromosomal DNA fragments using DNA probes representing ctxA, zot, ace and
      RS element revealed that the strains V2 and CG15 contained, at least, two
      complete copies of the CTX genetic element, while the strain V315-1 had three or
      more copies of the same. Presence of the RS element in these strains led to
      tandem duplication of the CTX genetic element in the chromosome of V2 and V315-1,
      but not in CG15 where the copies were likely to be present at different loci.
      These results also indicate the presence of additional copies of incomplete "core
      region' with zot and ace genes, but not ctxA, in strains V2 and CG15. The
      significance of these results in terms of the pathogenic and epidemic potential
      of V. cholerae strains is discussed.

PMID- 9140916
TI  - Molecular population genetic analysis of a Streptococcus pyogenes bacteriophage
      encoded hyaluronidase gene: recombination contributes to allelic variation.
AB  - Many strains of the human pathogenic bacterium Streptococcus pyogenes produce
      hyaluronidase, an enzyme that degrades hyaluronic acid, a major component of the
      extracellular matrix. Degradation of hyaluronic acid is thought to aid in host
      tissue invasion and dissemination of S. pyogenes. The molecular population
      genetics of the bacteriophage-encoded hyaluronidase gene (hyl) was analysed by
      sequencing the gene from 13 streptococcal strains representing seven well
      differentiated multilocus enzyme electrophoretic types and eight M or T protein
      serotypes. Substantial levels of allelic polymorphism were identified, and the
      analysis found strong statistical evidence that recombinational processes have
      contributed to the generation of molecular variation in this gene. A 111 base
      pair segment of hyl encoding a collagenous motif, that may bind collagen, was
      absent in a serotype M14 isolate and 13 serotype M18 multilocus enzyme
      electrophoretic type 20 strains examined. The analysis provides a molecular
      population genetics framework for studies examining the role of naturally
      occurring hyaluronidase variation in host-pathogen interactions.

PMID- 9140918
TI  - Insertional inactivation of streptolysin S expression is associated with altered
      riboflavin metabolism in Streptococcus pyogenes.
AB  - Transposon Tn916 mutagenesis was used to create a mutant of Streptococcus
      pyogenes M type 3, designated ISS417, in which the ability to produce
      streptolysin S (SLS) and several other exoproteins was impaired. Concomitantly,
      the mutant became dependent upon riboflavin for growth and was able to grow in
      Todd Hewitt broth (THB) when supplemented with riboflavin or riboflavinrich yeast
      extract. The parent strain was apparently able to utilize THB-derived components
      as a substitute for riboflavin, while the mutant was not. Although the parent
      strain grew well in synthetic medium, it was unable to produce SLS, except when
      it was supplemented with a small amount of THB. Thus, a component of THB was able
      to "trigger" SLS formation in the parent strain. The mutant grew well in this
      medium, but was unable to produce SLS even when it was supplemented with THB.
      Southern hybridization analysis revealed that the ISS417 mutant harbours a single
      transposon insertion in its chromosome. Phage transduction experiments showed
      that the riboflavin dependency and the inability to make SLS phenotypes are co
      transducible. The pleotrophic properties of the ISS417 mutant differ from those
      reported for insertional inactivation of the mga locus which regulates production
      of a number of surface proteins in S. pyogenes and the sar locus which regulates
      production of a number of exoproteins in Staphylococcus aureus. In view of the
      possibility that there exist a genetic linkage between the riboflavin
      biosynthetic pathway and expression of the oxygen-stable SLS, we hypothesize that
      SLS has a role in the growth economy of S. pyogenes.

PMID- 9140917
TI  - Cell mediated immunity induced in mice by HPV 16 L1 virus-like particles.
AB  - Recombinant human papillomavirus (HPV) type 16 L1 virus-like particles (VLPs)
      expressed in the baculovirus system were used to investigate the cellular immune
      response to human papillomavirus type 16. The cell-mediated immune response was
      evaluated through immunization of mice with HPV 16 L1 virus-like particles using
      a lymphoproliferation assay and cytokine production and cytometric analysis of
      lymphocyte subsets. A significant proliferative response was observed which was
      associated with secretion of both interferon-gamma and interleukin-2. FACS
      analysis of splenic lymphocytes revealed that CD8+ T-cells were increased in the
      immunized mice. These results demonstrate that HPV 16 L1 VLPs induce a T-cell
      response characterized by a Th1 profile and confirm that the HPV 16 VLP is a
      reasonable candidate for vaccine development.

PMID- 9140919
TI  - The ability of periurethral Escherichia coli to grow in a voiding system is a key
      for the dominance of E. coli cystitis.
AB  - The generally accepted concept of the pathogenesis of cystitis is that bacteria
      on the periurethra migrate via the urethra to the bladder urine. To explore why
      Escherichia coli is the dominant organism isolated from cystitis, we examined two
      potential mechanisms that might account for the dominance of E. coli as the
      etiologic agent in cystitis in prepubertal, non-sexually active girls. First, the
      frequency of carriage of aerobic bacteria on the periurethra of two populations
      healthy girls and girls after their first episode of cystitis was determined.
      Second, the survival capability of periurethral bacteria in urine under voiding
      conditions was examined. Two voids were simulated over 6 h by 10(2) dilution. A
      control was run in broth instead of urine. We found that Gram-positive bacteria,
      particularly coagulase-negative staphylococci, were much more common on the
      periurethra than E. coli. E. coli did grow well in urine in an in vitro voiding
      system whereas most Gram-positive bacteria did not. Growth in urine despite
      voiding may be the key reason for the dominance of E. coli in cystitis.

PMID- 9140920
TI  - Cloning and nucleotide sequence analysis of a Brucella abortus gene encoding an
      18 kDa immunoreactive protein.
AB  - A DNA fragment encoding an approximately 18 kDa protein from Brucella abortus
      strain 2308 was cloned and expressed in Escherichia coli. This recombinant
      protein, designated BA18K, reacted in Western blot analysis with sera obtained
      from experimentally and naturally infected animals including mice, goats, dogs
      and humans. Restriction enzyme analysis of the plasmid (pBA28) encoding BA18K
      revealed the presence of an approximately 8.7 kbp Sau3A genomic DNA fragment
      within the vector and subsequent subcloning and Western blot analysis limited the
      region encoding BA18K to an approximately 3.0 kbp Pst 1 DNA fragment. DNA
      sequence analysis of this region identified an open reading frame capable of
      encoding a protein of 177 amino acids with a predicted relative molecular mass of
      17529. Comparison of the deduced amino acid sequence of BA18K with those in the
      protein sequence databases yielded no homology with previously described proteins
      from other bacterial genera. These searches did, however, indicate that BA18K is
      identical to the previously described outer membrane protein (OMP) from B.
      abortus strain 544 designated Omp 19.

PMID- 9140921
TI  - Mutations in the f165(1)A and f165(1)E fimbrial genes and regulation of their
      expression in an Escherichia coli strain causing septicemia in pigs.
AB  - Transposon (TnphoA) mutagenesis was used to study the expression of F165(1)
      fimbriae, related to Prs fimbriae, in the pathogenic Escherichia coli strain 5131
      (O115:K "V165":F165). This strain causes septicemia in swine and also expresses
      F165(2) fimbriae, related to F1C. Adhesin-defective mutants from the wild-type
      pathogenic strain were produced and TnphoA insertions were localized either in
      the f165(1)A gene, which encodes the major fimbrial subunit or in the f165(1)E,
      gene, which encodes a minor fimbrial subunit. TnphoA gene fusions were used to
      measure expression of F165(1) fimbrial genes. Similar pattern of regulation of
      expression was observed in both f165(1)A and f165(1)E genes. Optimal expression
      of F165(1) fimbriae was obtained on solid minimal medium. Production of F165(1)
      fimbriae was negatively regulated by addition of glucose, leucine or alanine to
      the media, by growth at 18 degrees C, and by pH above or below 7.0.

PMID- 9140922
TI  - Role of bacterial metabolism and physiology in the pathogenesis of Clostridium
      difficile disease.

PMID- 9140923
TI  - The histological correlates of cellular detoxification mechanism.

PMID- 9140924
TI  - Conjugation of glutathione with the reactive metabolites of 1, 1-dichloroethylene
      in murine lung and liver.
AB  - Exposure to 1,1-dichloroethylene (DCE) elicits lung and liver cytotoxicities that
      are manifested in bronchiolar Clara cell injury and centrilobular necrosis,
      respectively. The tissue damage is associated with cytochrome P450-dependent
      bioactivation of DCE to reactive intermediates, and is consistent with the
      finding that the target cells coincided with the sites of high concentrations of
      cytochrome P450 enzymes. The metabolites formed from DCE bind covalently to
      cellular macromolecules, and the extent of binding and cell damage are inversely
      related to the content of intracellular glutathione (GSH). Histochemical studies
      showed that staining for GSH in the lung is localized in the bronchiolar
      epithelial and alveolar septal cells, with relatively strong staining in the
      Clara cells. In the liver, staining is observed rather uniformly in hepatocytes
      distributed across the hepatic lobule. Depletion of GSH correlates with the Clara
      cell damage and centrilobular necrosis observed in the lung and liver,
      respectively. The primary metabolites of DCE formed in lung and liver microsomal
      incubations have been identified as DCE-epoxide, 2,2-dichloroacetaldehyde and 2
      chloroacetyl chloride. All are electrophilic metabolites that form secondary
      reactions including conjugation with GSH. Results of our studies indicated that
      the DCE-epoxide is the major metabolite forming conjugates with GSH, and this
      reaction is likely responsible for the depletion of GSH observed in vivo. Our
      findings support the premise that, following depletion of intracellular GSH,
      metabolites of DCE including the DCE-epoxide bind to cellular proteins, a process
      which leads to cell damage and suggests that conjugation with the thiol
      nucleophile represents a-detoxification mechanism.

PMID- 9140925
TI  - Intranuclear distribution, function and fate of glutathione and glutathione-S
      conjugate in living rat hepatocytes studied by fluorescence microscopy.
AB  - The availability of fluorescent probes to detect soluble and protein-bound thiols
      has made it possible to investigate some aspects of reduced glutathione (GSH)
      metabolism and function in intact rat hepatocytes and in hepatocyte nuclei.
      Monochlorobimane (BmCl) has been employed to study the subcellular
      compartmentation of GSH and the formation and fate of the BmCl-GSH conjugate. The
      occurrence of relatively high concentrations of GSH within the nuclear matrix has
      been inferred from fluorescence quantitation using image analysis. Concomitant
      biochemical studies have revealed the presence of a GSH-stimulated ATP hydrolysis
      and of an ATP-stimulated GSH accumulation in isolated nuclei, providing the
      molecular basis for nuclear glutathione compartmentation. The contemporary use of
      fluorescent probes to label nuclear free sulfhydryl groups, proteins and
      chromatin status led to the demonstration that intranuclear accumulation of
      glutathione may modulate the thiol/disulfide redox status of nuclear proteins and
      control chromatin compacting and decondensation.

PMID- 9140926
TI  - A review of drug-induced lysosomal disorders of the liver in man and laboratory
      animals.
AB  - Lysosomotropic agents are selectively taken up into lysosomes following their
      administration to man and animals [de Duve et al. (1974) Biochem. Pharmacol.
      23:2494-2531] The effects of lysosomotropic drugs studied in vivo and in vitro
      can be used as models of lysosomal storage diseases. These agents include many
      drugs still used in clinical medicine: aminoglycosides used in antibiotics
      [Tulkens (1988)]; phenothiazine derivatives; such antiparasitic drugs as
      chloroquine and suramin; antiinflammatory drugs like gold sodium thiomalate; and
      cardiotonic drugs like sulmazol [Schneider (1992) Arch. Toxicol. 66:23-33]. Side
      effects to these drugs can be caused by their lysosomotropic properties. In
      addition to drugs, other compounds to which man and animals are exposed (e.g.,
      metals, cytostatics, vitamins, hormones) are also lysosomotropic. Liver cells,
      especially Kuppfer cells, are known to accumulate lysosomotropic agents. Here we
      review studies which evaluate lysosomal changes in the liver following
      administration of lysosomotropic agents to experimental animals, and relate them
      to toxic side-effects or pharmacological action, as was suggested by de Duve et
      al. (1974). Common features of lysosomal changes include, the overload of liver
      lysosomes by non-digestible material; increased size and number of liver
      lysosomes; inhibition of several lysosomal enzymes; secondary increase in the
      activity of some lysosomal enzymes; increased autophagy, and fusion disturbances.
      There was no significant change in endocytosis, except for an increase in the
      Triton WR 1339 model.

PMID- 9140927
TI  - Responses of rat nasal epithelium to short- and long-term exposures of ozone:
      image analysis of epithelial injury, adaptation and repair.
AB  - This article reviews the use of computerized image analysis and standard
      morphologic techniques to characterize the responses of nasal epithelium in
      laboratory rats to single or repeated exposures to a common urban air-pollutant,
      ozone. Alterations in the number and composition of the epithelial cell
      populations after either short- or long-term exposures are described. The
      principal nasal epithelial alteration induced by repeated exposures to this
      irritating, oxidant pollutant is mucous cell metaplasia (i.e., transformation of
      airway epithelium, normally devoid of mucous cells, to a secretory epithelium
      containing numerous mucus-secreting cells). This metaplastic change, induced by
      acute or chronic ozone exposures, has been morphometrically examined at various
      times post-exposure. In this article, we describe our current understanding of
      the pathogenesis and persistence of ozone-induced mucous cell metaplasia in nasal
      epithelium based on the results of these morphometric studies.

PMID- 9140929
TI  - Secondary ion mass spectrometry (SIMS) microscopy: a new tool for pharmacological
      studies in humans.
AB  - The secondary ion mass spectrometry (SIMS) microscope has opened new fields in
      biological investigation because of its ability to map chemical elements that are
      either naturally present in tissue or introduced for diagnostic or therapeutic
      purposes. In this review, we will describe our attempts to localise and quantify
      antitumor drugs in histological sections to better evaluate successful early
      cancer treatment. Detection is dependent on the presence of chemical elements in
      the drug structure, for example halogens (F, Br, I, At) which are imaged and
      quantified within the nuclei. Our methodological approach combines the results
      obtained with ionic and photonic microscopes on serial sections. Thus, the
      different structures in tumor tissue (blood vessels and cells) can be identified
      and drug localisation visualized. Using embedded samples, we demonstrate that
      both fluorine (19F) in 5-Fluorouracil and iodine (127I) in 4'-iododeoxyrubicin
      can be mapped in human biopsy material obtained after in vivo chemotherapy.

PMID- 9140928
TI  - Complementary advantages of fluorescence and SIMS microscopies in the study of
      cellular localization of two new antitumor drugs.
AB  - Low light level fluorescence microscopy studies have been carried out on MCF7-P
      human mammary tumor cells to localize the intracellular distribution of two new
      anticancer drugs, Pazelliptine and Intoplicine, which are currently under
      clinical evaluation. These two molecules are thought to act at the nuclear level,
      through DNA topoisomerase interactions. Because fluorescence of these compounds
      appears strongly quenched by intercalation in double strand DNA, secondary ion
      mass spectrometry (SIMS) imaging was used to check the presence of the drugs in
      the nuclear compartment. In spite of chemical structure similitudes, pazelliptine
      and intoplicine appear to be distributed in quite different ways within the
      cells. Incubation for 1 and 24 hours also allowed us to bring to light strong
      differences in the distribution kinetics. Pazelliptine quickly enters into the
      nucleoli but is no longer present in the nucleus after 24 hours incubation.
      Intoplicine was not detected by fluorescence in the nucleus, however SIMS
      microscopy allowed us to show its accumulation within this cellular compartment
      as a function of time of exposure. This study shows the complementarity of
      fluorescence and SIMS microscopies.

PMID- 9140930
TI  - Imaging of BrdU-labeled human metaphase chromosomes with a high resolution
      scanning ion microprobe.
AB  - Detailed maps of the A-T distribution within human mitotic chromosomes labeled
      with BrdU are obtained with a high resolution scanning ion microprobe through the
      detection of bromine by imaging secondary ion mass spectrometry (SIMS).
      Corresponding maps of the emission loci of the molecular ion CN- describe the
      overall DNA, RNA and protein distribution in the chromosomes. Several chromosome
      preparations exhibit base-specific banding patterns (SIMS-bands) which mimic the
      well known G- or Q-bands resulting from conventional staining methods for optical
      microscopy. SIMS-bands are more noticeable in mitotic cells at the first cell
      cycle and after in situ denaturation or Giemsa staining. Sister chromatid
      exchanges (SCE) at the second cell cycle and beyond, occurring both spontaneously
      and promoted following cell culture exposure to the chemical aphidicolin (an
      inhibitor of DNA replication), can be visualized readily from the relative label
      signal intensities between sister chromatids. The comparison of base-specific
      label maps with CN- maps, in conjunction with the appearance of base-specific
      banding patterns, is informative about protein survival and/or removal following
      different chromosome preparation protocols. In addition, the resulting
      condensation state of the chromosomes can be appraised during SIMS analysis from
      the sample topography (imaged via the collection of mass-unresolved secondary
      ions). We demonstrate that imaging SIMS is a powerful complement to existing
      methods for the study of banding mechanisms and for the elucidation of chromosome
      structure. The advantages of this novel approach to the systematic and
      quantitative study of cytogenetic phenomena and methodologies are still largely
      untapped.

PMID- 9140932
TI  - Models of exocrine pancreatic pathologies: a microscopical point of view.
AB  - The objective of this review is to emphasize the contribution of optical and
      electronic microscopy to the study of the normal and pathological rat pancreas.
      These basic techniques used to explore the pancreatic morphology are capital to
      precisely localize specific enzymes or proteins in cellular subcompartments, to
      establish the normal or the pathological state of the gland, and to detect and
      describe unusual structures that appear under certain experimental conditions.

PMID- 9140931
TI  - Role of alveolar macrophage lysosomes in metal detoxification.
AB  - The intracellular behaviour of different toxic mineral elements inhaled as
      soluble aerosols or as insoluble particles was studied in the rat by electron
      microscopy, electron probe microanalysis, and electron microdiffraction. This
      study showed that, after inhalation, aerosols of soluble elements like cerous
      chloride, chromic chloride, uranyl nitrate, and aluminium chloride, are
      concentrated in the lysosomes of alveolar macrophages and are precipitated in the
      lysosomes in the form of insoluble phosphate, probably due to the activity of
      acid phosphatase (intralysosomial enzyme). Also, after inhalation of crystalline
      particles that are insoluble or poorly soluble in water such as the illites
      (phyllosilicates), ceric oxides (opaline), and industrial uranium oxides (U3O8),
      the small crystals are captured by the alveolar macrophage lysosomes and
      transformed over time into an amorphous form. This structural transformation is
      associated with changes in the chemical nature of particles inhaled in the oxide
      form. Microanalysis of amorphous deposits observed after inhalation of uranium or
      ceric oxides has shown that they contain high concentrations of phosphorus
      associated with the initial elements cerium and uranium. These different
      processes tend to limit the diffusion of these toxic elements within the
      organism, whether they are inhaled in soluble form or not.

PMID- 9140933
TI  - Preparation of single-celled marine dinoflagellates for electron microscopy.
AB  - Electron microscopy has been used successfully to study and identify single
      celled marine dinoflagellates including parasitic ones and others, such as those
      that cause red tide. Delicate cells can be preserved for scanning electron
      microscopy with a combined glutaraldehydeosmium tetroxide mixture that is
      adjusted for the osmolality of the medium. The protocol allows resolution of fine
      morphological features. Preservation for transmission electron microscopy can be
      accomplished with a standard glutaraldehyde fixation and osmium-tetroxide post
      fixation in a suitable buffer, but again, the osmolality of the mixture must be
      adjusted. The protocol allows ultrastructural resolution of vesiculated cells and
      has been modified for small sample sizes.

PMID- 9140934
TI  - Influence of material properties on TEM specimen preparation of thin films.
AB  - Several factors must be taken into account when deciding which specimen
      preparation technique(s) to use. These factors include the amount of material
      available, ease of preparing this material due to its properties and familiarity,
      location and size of the region of interest, amount of information sought,
      facilities accessible, and time available by the researcher to devote to the
      preparation of the specimen. The more popular specimen preparations for thin
      films, namely, electropolishing, cleaving, crushing, mechanical thinning followed
      by ion milling, and ultramicrotomy are discussed and the more unusual techniques
      such as extraction/replication, photochemical etching, lithography and reactive
      ion etching (RIE), chemically assisted ion beam etching (CAIBE), and precision
      polishing-based techniques are described. Their advantages and disadvantages in
      the context of the above factors are discussed. Suggestions for increasing one's
      success rate in preparing specimens are given. The role of transmission electron
      microscopy (TEM) analysis is considered since it rarely stands in isolation from
      other physical analytical techniques, nor is it often used as a quick diagnostic
      tool. Conservation of material by the minimization of the amount of material used
      (or destroyed) by TEM specimen preparation, and conservation of one's time by
      performing TEM analysis only on "worthy" samples should be given maximum
      consideration.

PMID- 9140935
TI  - Preparation of cross-sectional TEM samples for low-angle ion milling.
AB  - The ideal ion-milled transmission electron microscope (TEM) sample would contain
      large, thin areas in selected regions, minimal top and bottom surface
      amorphization, and minimal preferential etching of adjacent materials. This
      desire has led to studies of these effects and improvements in designs and
      techniques for ion mills. Minimizing the incident angle of the ion beam to the
      surface of the sample has been found to be one of the most effective techniques
      for fulfilling these requirements. A new generation of ion mills has recently
      been designed to allow low-angle ion milling for the production of very high
      quality cross-sectional TEM samples. To take advantage of the low-angle ion
      milling capabilities and high-powered ion sources in these mills, new sample
      preparation techniques are required. In this paper, a simple technique of
      mounting material in a specialized titanium grid for cross-sectional TEM sample
      preparation is presented. This technique is designed to take full advantage of
      the powerful capabilities of these new low-angle ion mills.

PMID- 9140936
TI  - Cross-section TEM sample preparation of multilayer and poorly adhering films.
AB  - The preparation of TEM cross-section samples from multilayer films or poorly
      adhering films is discussed in detail in a step-by-step approach designed to
      enable a competent experimentalist to reproduce the technique. The samples are
      mounted on an aperture grid and mechanically polished to 2-3 microns in
      thickness. After ion beam milling for a short period of time (less than 1 hour),
      a large electron transparent area is obtained. Examples from several thin film
      systems are discussed.

PMID- 9140937
TI  - Application of the small-angle cleavage technique to thickness measurement of TEM
      samples.
AB  - In modelling transmission electron microscopy (TEM) images with the dynamical
      theory of electron diffraction, the sample thickness at the region of interest
      must be accurately known. A technique of sample preparation for cross-sectional
      single-crystal samples has been developed to provide this information. This
      technique, based on the small-angle cleavage technique, can allow a direct
      measurement of the sample thickness at the region where cross-sectional TEM
      analysis has been undertaken. Several cross-sectional samples of GaAs-based
      multiple quantum wells were prepared with parallel cleaved faces and thicknesses
      in the range of 50 to 200 nm. The samples were initially mounted so that cross
      sectional images were obtained, then on suitable samples the mount was adjusted
      to obtain a plan view image of the same area. With suitable care, this technique
      provided an accurate thickness measurement of a cross-sectional region of a
      sample, which allowed subsequent modelling and analysis.

PMID- 9140938
TI  - Plan view TEM sample preparation for non-continuous and delaminating thin films.
AB  - The preparation of plan view samples for TEM examination is generally a
      straightforward process except where the film delaminates from the substrate or
      is non-continuous. A method is described where film is first stabilised using an
      epoxy, then transferred to an aperature grid and ion milled to produce an
      electron transparent sample. This technique provides a relatively simple and fast
      method to prepare these types of films, using the standard equipment and supplies
      found in most TEM sample preparation laboratories.

PMID- 9140939
TI  - Ultramicrotomy of powder material for TEM/STEM study.
AB  - This paper summarizes methods conventionally used to prepare thin foil samples of
      powder materials for transmission electron microscopy (TEM) and introduces
      another variant, ultramicrotomy, for the preparation of TEM samples of industrial
      dust powder. The choice of ultramicrotoming in the present work was based on two
      features of this technique: (1) it can produce thin-sectioned specimens with a
      uniform thickness; (2) it can retain the original elemental distribution in
      phases of the sample during sectioning. Dust powder preparation and the
      sectioning procedure are described in this paper. The results of the method are
      illustrated by examples of TEM/STEM micrographs of industrial dust.

PMID- 9140940
TI  - Dynamic imaging of structural changes in silver catalysts by environmental
      scanning electron microscopy.
AB  - Polycrystalline silver catalysts are used extensively for the partial oxidation
      of methanol to formaldehyde, which is then primarily incorporated in the
      synthesis process for adhesives and resins. In order to maximize formaldehyde
      production it is essential to gain a comprehensive understanding of the complex
      microstructural changes which occur in the catalyst during reaction conditions.
      However, conventional electron microscopic techniques are incapable of imaging
      catalysts at high temperatures and in the presence of a gaseous atmosphere.
      Therefore, an environmental scanning electron microscope (ESEM) has been used to
      image polycrystalline silver catalysts during simulated industrial conditions.
      The most dramatic effect of heating various catalysts to 700 degrees C in the
      ESEM chamber was the formation of "pinholes" in the silver surface. These
      "pinholes" occur at specific temperatures and are inherently associated with the
      catalytic process, resulting from near-surface explosions caused by subsurface
      hydroxyl recombination. Of particular interest was the nature and location of the
      holes, which preferentially occur in the vicinity of surface defects such as
      platelets and edge structures. To the best of our knowledge, this study
      represents the first time that the progress of a catalytic reaction has been
      observed under in situ conditions by scanning electron microscopy.

PMID- 9140941
TI  - A solvent-based fixative for electron microscopy to improve retention and
      visualization of the intestinal mucus blanket for probiotics studies.
AB  - Samples of pig small intestine, cecum, and large intestine were prepared for
      scanning electron microscopy (SEM), concentrating on mucus blanket retention and
      visualization. Samples were fixed using three aqueous-based fixatives which
      included a standard glutaraldehyde fixative alone as the control and the standard
      fixative formulation with either ruthenium red or alcian blue added and using one
      solvent-based fixative, osmium tetroxide dissolved in FC-72 (a degreasing
      fluorocarbon solvent produced by 3M Canada, Inc.), which had been successfully
      used by Sims et al. [(1991) Biotech. Histochem., 66:173-180] to preserve tracheal
      mucus of nonhuman mammals. Pig intestine samples prepared using the solvent-based
      fixative retained a contiguous mucus blanket, while the aqueous-based treatments
      retained only patchy or fibrous remnants to a degree depending on fixative
      composition and intestinal site. We conclude that preparation of the pig
      intestinal mucus layer using the solvent-based fixative suggested by Sims et al.
      (1991) preserves the mucus blanket in its entirety and gives superior results to
      aqueous-based fixatives containing the standard additives ruthenium red and
      alcian blue. We recommend that this anhydrous fixation, which requires only a
      slight modification from standard conditions, be adopted when mucus layer
      retention and visualization is important, as in the field of probiotics.
      Overcoming this major technical obstacle will now allow electron microscopy (EM)
      to once again provide new in situ information in this reemerging field.

PMID- 9140942
TI  - Conformation of Lac repressor tetramer in solution, bound and unbound to operator
      DNA.
AB  - We tested whether the Steitz et al. [(1974) Proc. Natl. Acad. Sci. U.S.A., 71:593
      597] model of lactose repressor (LacR) (14 x 6.0 x 4.5 nm) represented the shape
      of free or operator-bound LacR in solution. The model predicts a 14 nm length for
      bound LacR. Direct measurement, using Pt-C shadow width standards, was 9.6 +/-
      0.2 nm long. Using the Steitz model, we generated a distribution of measurements
      and converted them into a distribution of shadow widths using gold ball
      standards. Direct measurement of LacR produced a narrower shadow width
      distribution with a larger mean size than the Steitz model predicted. Measurement
      along two orthogonal axes of negatively stained LacR images generated a size
      distribution, also converted into a shadow width distribution using the gold ball
      standards. Since the experimental shadow width distribution exactly matched the
      shadow width distribution derived theoretically from negatively stained LacR, our
      negative-stained images are representative of LacR's conformation in solution.
      Approximately 56% of negatively stained LacR had a V-shaped fold around an axis
      orthogonal to its length, bringing the DNA binding domains of each dimer
      adjacent. This open end of the V binds single operator DNA. The other 44% of the
      LacR tetramer is in the extended form with its DNA binding sites at opposite
      ends. Although the V-shaped conformation has a closed hinge with the dimers
      associated along a side, the extended open-hinged state remains important since
      LacR must bind two distant operator sites for full repression. Our measurements
      predict the normal presence of both conformations in nearly equal amounts,
      suggesting that both are equally active in repressing the lac operon.

PMID- 9140943
TI  - Image contrast in sections of epoxy resin-embedded biological material:
      maintenance of a proper anhydride-epoxy ratio during tissue impregnation.
AB  - Epoxy resins are mixtures of several components formulated in exact proportions
      to assure proper polymerization. It is necessary that this composition be
      maintained throughout the tissue being infiltrated to avoid embedding artifacts.
      Unfortunately, the separate resin components will not penetrate the tissue at the
      same rate unless they all have the same viscosity and molecular size. Failure to
      meet these criteria will result in component separation during tissue
      infiltration and may result in severe embedding defects. This and several
      ancillary problems such as low tissue contrast, damage to diamond knives, and
      poor postsection staining are explored in this brief discussion.

PMID- 9140944
TI  - Paraformaldehyde effect on ruthenium red and lysine preservation and staining of
      the staphylococcal glycocalyx.
AB  - The utility of lysine in glutaraldehyde-ruthenium red fixatives for the
      preservation and/or staining of the fibrous staphylococci glycocalyx was improved
      by inclusion of paraformaldehyde. Short, 20 min prefixation times for
      paraformaldehyde-glutaraldehyde fixatives containing lysine, with or without
      ruthenium red, were compared to an extended overnight fixation. Samples were
      often lost in fixatives that did not contain paraformaldehyde at extended
      fixation times hampering the effective use of these fixatives for clinical or
      environmental applications. Inclusion of paraformaldehyde in the fixation with
      lysine permitted longer fixation times as well as stabilized the staphylococcal
      glycocalyx. Thus, the technical usefulness of fixatives employing lysine was
      significantly improved.

PMID- 9140945
TI  - Ultrastructure of the aqueous lining layer in hamster airways: is there a two
      phase system?
AB  - For particle retention and clearance, the structure and surface properties of the
      airway lining layer are important. Due to difficulties of its preservation,
      structural analysis has been hampered, and, hence, the existence of two distinct
      and continuous phases and how much osmiophilic material is available are unclear.
      It was the objective of this study to investigate the ultrastructure of the
      aqueous lining layer in the intrathoracic conducting airways of hamsters. By
      means of transmission electron microscopy, we investigated the ultrastructure of
      the airway lining layer in hamsters whose lungs have been fixed by the
      application of fixative dissolved in nonpolar fluorocarbon, either by
      instillation via the trachea or injection into the gas exchange parenchyma,
      together with intravascular perfusion of aqueous fixatives. The results were
      compared to lungs fixed by intravascular perfusion only. In twelve hamsters, the
      airway lining layer was found to consist of an aqueous phase and was coated by an
      osmiophilic film that follows fairly closely the upper-extending contours of
      cilia protruding from epithelial cells. Substantially less osmiophilic material
      was preserved in extrapulmonary airways and when nonaqueous fixative was
      injected. We found that the aqueous lining layer of the intrathoracic airways in
      hamsters essentially surrounds and covers the cilia, the microvilli, and any
      other structures like macrophages or deposited particles contained in it and is
      coated by an osmiophilic film of variable thickness. In healthy animals, a gel
      phase is expected to be very thin, not clearly separated from the periciliary
      fluid, and located just beneath the osmiophilic film.

PMID- 9140946
TI  - Low temperature HREM observations of structural fluctuations in small particles:
      evidence for a thermally activated process.

PMID- 9140947
TI  - Simple goniometric search for electron microscopy.
AB  - We developed a special software to memorize specific points on a grid for later
      fine analysis. This program is based on a goniometry search, and implemented on
      the PC coupled microscope. This allows automatic shifting of the grid, but it can
      also be programmed on a simple pocket calculator.

PMID- 9140948
TI  - Maximizing flap survival in a prefabrication model using exogenous and endogenous
      bFGF: a new approach.
AB  - Flap prefabrication is dependent on the neovascular response that occurs between
      the implanted arteriovenous pedicle and the recipient tissue. Augmentation of
      this neovascular response with angiogenic growth factors would maximize flap
      survival and minimize the interval between pedicle implantation and flap
      rotation. Maximizing the biologic activity of endogenous growth factors would
      likewise positively impact upon flap survival. This study examined the role of
      basic fibroblast growth factor, a known potent angiogenic growth factor, on flap
      survival in a rabbit ear prefabrication model. Sucrose octasulfate, a substance
      that binds basic fibroblast growth factor, stabilizes it, and protects it from
      degradation, was also studied to determine its impact on flap survival. Flap
      survival was increased using basic fibroblast growth factor, sucrose octasulfate,
      and the two substances combined together. The use of substrates designed to
      maximize the biologic activity of endogenous growth factors, rather than relying
      on the artificial addition of exogenous growth factors, represents a new approach
      in the search for methods that will improve flap survival.

PMID- 9140949
TI  - Use of distal arteries for microvascular reconstruction in forearm and hand
      surgery.
AB  - Three techniques that use distal arteries for microvascular reconstruction in
      forearm and hand surgery are described: (1) distal based supply from the deep
      branch of the radial artery, (2) proximal reversal of the radial artery, and (3)
      distal based supply from the ulnar artery. Nine cases are described to illustrate
      the use of these techniques: three vascularized bone grafts, three toe-to-hand
      transfers, one free cutaneous flap, one brachial artery reconstruction, and one
      replantation of an amputated palm. The technique offers a number of advantages:
      (1) it eliminates the need for vein grafts, (2) it requires only a single
      arterial microvascular anastomosis, (3) it minimizes microvascular size
      discrepancies, (4) the distal artery can be prepared in the same operative field
      as the rest of the reconstruction, and (5) the technique enables an undamaged
      artery to be brought into a zone of trauma and used as a recipient vessel. The
      technique has the disadvantage that it sacrifices part of the collateral
      circulation to the hand and it is therefore important to check the blood supply
      to the hand preoperatively.

PMID- 9140950
TI  - A thinned forearm flap transfer to the nose.
AB  - We employed a forearm flap that had been thinned through primary defatting for
      nasal covering in three cases to reduce the need for secondary revision. Partial
      flap loss did occur in one case due to subcutaneous vascular plexus injury, but
      acceptable results were obtained in the remaining two cases. Donor site concave
      deformities were substantially reduced by removal of fat from around the flap
      margin. Great care must be taken during surgery to avoid damage to the small
      vascular network around the pedicle to prevent flap necrosis.

PMID- 9140951
TI  - The influence of skin flap ischemia on serum nitric oxide concentrations.
AB  - Nitric oxide (NO), identified as a mediator of endothelium-dependent relaxation
      of vascular smooth muscle, is known to cause a number of inflammatory diseases,
      especially ischemia-reperfusion injury. This experimental study, using a rabbit
      epigastric island flap, was designed to investigate whether skin flap ischemia
      followed by reperfusion influences serum NO concentrations. In addition, the
      author investigated the effects of NO synthase inhibitors and heparin on skin
      flap ischemia. Serum NO concentrations after 15, 30, 45, and 60 minutes of
      ischemia followed by reperfusion were significantly increased compared with non
      ischemic controls and elevated flaps. On the other hand, serum NO concentrations
      were suppressed in nitro-amino-methyl-L-arginine- and aminoguanidine-treated
      animals. Furthermore, administration of heparin increased serum NO concentrations
      in controls and animals with elevated flaps, but decreased serum NO
      concentrations in ischemic flaps with subsequent reperfusion. These results
      suggest that NO is one of the factors responsible for ischemia-reperfusion injury
      and that NO synthase inhibitors and heparin may protect against such injury.

PMID- 9140952
TI  - Heat-induced tissue fusion for microvascular anastomosis.
AB  - Laser tissue welding was compared with a crude method of bipolar coagulator
      generated heat application for achieving the same heat-induced welding effect in
      rat microarterial anastomoses. Rat femoral arteries were anastomosed with three
      triangulated stay sutures and subsequent laser welding or bipolar coagulator
      application between each pair of stitches. Control (non-welded) vessels received
      nine stitches placed circumferentially. Laser-welded vessel patency at 1 or more
      days postoperatively was 90% (65/72) for vessels treated with 0.1-second laser
      pulses, not significantly different from controls (100%; 16/16) or coagulator
      welded anastomoses (88%; 14/16). Pseudoaneurysm rates were higher in the welded
      vessels (9% and 14% for laser- and coagulator-treated vessels, respectively) than
      in controls (0%). Histologic and electron microscopic evaluation revealed good
      healing with no apparent differences between laser- and coagulator-welded
      repairs. These findings suggest that laser application for microvascular tissue
      welding is similar to poorly controlled welding with a bipolar coagulator.

PMID- 9140953
TI  - Experience of a new surgical procedure for the treatment of unilateral
      obstructive lymphedema of the lower extremity: adipo-lymphatico venous transfer.
AB  - We report five cases of adipo-lymphatico venous transfer (ALVT) performed to
      treat unilateral obstructive lymphedema of the lower extremity. ALVT is a
      surgical procedure that utilizes the long saphenous vein and its surrounding
      lymphatic tissue from the unaffected limb for the treatment of lymphedema. Since
      ALVT does not necessitate anastomoses of lymphatic vessels, it can be performed
      regardless of the severity and duration of lymphedema, and stable long-term
      results can be obtained when the transferred lymphatic tissue shows viability.

PMID- 9140954
TI  - Harvesting of the sural nerve with a tendon stripper.
AB  - The nerve most commonly used for peripheral nerve reconstruction is the sural
      nerve. The nerve can be dissected free through one long calf incision, by
      utilizing multiple small incisions, or by using a tendon stripper. We studied 12
      above-knee amputation specimens harvesting the nerve in the ways described. We
      found that the length of nerve harvested averaged 32, 36, and 25 cm for the open,
      limited open, and stripper techniques, respectively. Epineurial damage occurred
      with the stripper, but no perineurial damage was documented histologically. We
      concluded that the closed method (stripper) of harvesting sural nerve would
      provide quality graft material, but of unpredictable length. When reliably long
      segments of nerve are required, at least a limited open or an open approach for
      harvest is recommended.

PMID- 9140955
TI  - Antibody formation in the transplanted spleen: a simple method of splenic
      transplantation in the rat using the cuff technique.
AB  - To study whether transplanted spleens produce antibodies or not, a simplified
      model of spleen transplantation using the cuff technique was developed. The whole
      spleen with vascular pedicles was implanted in the syngeneic DA (RT1a) rat
      combination, using the cuff technique applied to the renal artery and vein of the
      recipient. The functions of the grafted spleen were tested by antibody formation
      titers of antibody in the serum and plaque-forming cells in the graft spleen
      against xenogeneic [BALB/c (H-2d) mouse] antigen. The grafted spleens included a
      number of plaque-forming cells, as did the host spleen. This report shows direct
      evidence that vascularized splenic grafts produced antibodies. The technique is
      described in detail.

PMID- 9140956
TI  - Comparison of arterial and venous patency in a rat model of subendothelium
      stimulated thrombosis.
AB  - The effectiveness of anticoagulants and platelet aggregation inhibitors was
      compared using comparable rat models of arterial and venous thrombosis. A
      mechanical endothelium-denuding injury was created on the lumenal surface of
      donor Lewis rat carotid arteries. These were cut into 4-5 mm lengths and grafted
      into femoral veins and arteries of recipient syngeneic rats using microvascular
      anastomotic techniques. Recipients received either systemic heparin, or aspirin
      with dipyridamole, or saline (control). In the arteries, the 1-day patency rate
      was 94% in the heparin-treated rats, but only 50% in the aspirin/dipyridamole
      group and 44% in the control group. The venous patency rate was 56% in the
      heparin group, 31% in the aspirin/dipyridamole group, and 0% in the control
      group. This unique model for comparing thrombosis in arteries and veins shows
      that anticoagulation is more effective than inhibition of platelet aggregation in
      the rat arterial system, with less of a differential effect in the venous system.

PMID- 9140957
TI  - Peroneal osteocutaneous flap raised on reconstructed popliteal artery for delayed
      union following open tibial fractures.
AB  - Two cases of delayed union following type IIIC open tibial fracture were treated
      by a pedicled peroneal osteocutaneous flap raised on reconstructed popliteal
      vessels. Dissection of the peroneal vessels from the already traumatized
      extremity was tedious, but this technique provided a reliable vascularized skin
      and bone graft that was indispensable for the fracture healing. Peroneal
      osteocutaneous flaps raised on the reconstructed popliteal artery have not been
      reported to date; they appear to be a good alternative to free osteocutaneous
      flaps for non-union of the proximal tibia.

PMID- 9140958
TI  - In vitro platelet aggregation studies in microvascular surgery research: a method
      in the rat model.
AB  - There is now a growing awareness of the central role of platelet function in
      microvascular thrombosis. Platelet aggregation studies remain one of the most
      useful ways of studying platelet function and response to different stimuli. This
      brief communication highlights some of the main variables that can affect
      platelet aggregation in rats and emphasizes the existence of important
      differences in these variables compared with human platelet aggregation.

PMID- 9140959
TI  - Modifications to surgical practise.

PMID- 9140960
TI  - DnaA initiator--also a transcription factor.
AB  - The replication-initiator protein DnaA is ubiquitous in the eubacterial world. It
      binds to an asymmetric 9 bp consensus DNA sequence, the DnaA box. Besides its
      primary function as an initiator, it acts as a transcription factor that
      represses or activates several genes, or terminates transcription, depending on
      the location and arrangement of DnaA boxes.

PMID- 9140962
TI  - Functional importance of RNA interactions in selection of translation initiation
      codons.
AB  - RNA base pairing between the initiation codon and anticodon loop of initiator
      tRNA is essential but not sufficient for the selection of the 'correct' mRNA
      translational start site by ribosomes. In prokaryotes, additional RNA
      interactions between small ribosomal subunit RNA and mRNA sequences just upstream
      of the start codon can efficiently direct the ribosome to the initiation site.
      Although there is presently no proof for a similar important ribosomal RNA
      interaction in eukaryotes, the 5' non-coding regions of their mRNAs and
      'consensus sequences' surrounding initiation codons have been shown to be strong
      determinants for initiation-site selection, but the exact mechanisms are not yet
      understood. Intramolecular base pairing in mRNA and participation of translation
      initiation factors can strongly influence the formation of mRNA-small ribosomal
      subunit-initiator tRNA complexes and modulate translational activities in both
      prokaryotes and eukaryotes. Only recently has it been appreciated that
      alternative mechanisms may also contribute to the selection of initiation codons
      in all organisms. Although direct proof is currently lacking, there is
      accumulating evidence that additional cis-acting mRNA elements and trans-acting
      proteins may form specific 'bridging' interactions with ribosomes during
      translation initiation.

PMID- 9140961
TI  - H-NS: a modulator of environmentally regulated gene expression.
AB  - H-NS is a small chromatin-associated protein found in enterobacteria. H-NS has
      affinity for all types of nucleic acids but binds preferentially to intrinsically
      curved DNA. The major role of H-NS is to modulate the expression of a large
      number of genes, mostly by negatively affecting transcription. Many of the H-NS
      modulated genes are regulated by environmental signals, and expression of most of
      these genes is positively regulated by specific transcription factors. Therefore
      one of the purposes of H-NS could be to repress expression of some genes under
      conditions characteristic of a non-intestinal environment, but allow expression
      of specific genes in response to certain stimuli in the intestinal environment.
      The hns gene is autoregulated. In vivo the H-NS to DNA ratio is fairly constant
      except during cold shock, when it increases three- to fourfold. In this review we
      propose that only the preferential binding to intrinsically curved DNA plays a
      role under normal growth conditions, and we discuss the different mechanisms by
      which H-NS might affect gene expression and how H-NS could be involved in the
      response to different stress situations. Finally, we summarize the evolutionary
      and functional relationship between H-NS and the homologous StpA.

PMID- 9140963
TI  - SpoIIQ, a forespore-expressed gene required for engulfment in Bacillus subtilis.
AB  - A crucial step in converting an actively growing Bacillus subtilis cell into a
      dormant spore is the formation of a cell within a cell. This unusual structure is
      created by a phagocytosis-like process in which the larger mother cell
      progressively engulfs the adjacent smaller forespore. Only mutations blocking
      engulfment at an early stage and affecting genes expressed in the mother cell
      have been identified. Here we describe a new locus, spoIIQ, which is transcribed
      in the forespore and which encodes a membrane-bound protein required at a late
      stage of engulfment. Immunofluorescence microscopy analysis have shown that
      SpoIIQ is initially targeted to the septum at the boundary between the two cells
      and then spreads around the entire membrane of the forespore. Septum targeting
      requires only the first 52 residues of SpoIIQ as well as unidentified forespore
      specific components. Electron-microscopy studies of cells engineered to activate
      the mother-cell program of gene expression independently of the forespore
      indicate that other as yet uncharacterized genes are involved in engulfment and
      that this morphological process is driven from both sides of the forespore
      envelope.

PMID- 9140964
TI  - Characterization of the chemotaxis protein CheW from Rhodobacter sphaeroides and
      its effect on the behaviour of Escherichia coli.
AB  - In contrast to the situation in enteric bacteria, chemotaxis in Rhodobacter
      sphaeroides requires transport and partial metabolism of chemoattractants. A
      chemotaxis operon has been identified containing homologues of the enteric cheA,
      cheW, cheR genes and two homologues of the cheY gene. However, mutations in these
      genes have only minor effects on chemotaxis. In enteric species, CheW transmits
      sensory information from the chemoreceptors to the histidine protein kinase,
      CheA. Expression of R. sphaeroides cheW in Escherichia coli showed concentration
      dependent inhibition of wild-type behaviour, increasing counter-clockwise
      rotation and thus smooth swimming--a phenotype also seen when E. coli cheW is
      overexpressed in E. coli. In contrast, overexpression of R. sphaeroides cheW in
      wild-type R. sphaeroides inhibited motility completely, the equivalent of
      inducing tumbly motility in E. coli. Expression of R. sphaeroides cheW in an E.
      coli delta cheW chemotaxis mutant complemented this mutation, confirming that
      CheW is involved in chemosensory signal transduction. However, unlike E. coli
      delta cheW mutants, in-frame deletion of R. sphaeroides cheW did not affect
      either swimming behaviour or chemotaxis to weak organic acids, although the
      responses to sugars were enhanced. Therefore, although CheW may act as a signal
      transduction protein in R. sphaeroides, it may have an unusual role in
      controlling the rotation of the flagellar motor. Furthermore, the ability of a
      delta cheW mutant to swim normally and show wild-type responses to weak acids
      supports the existence of additional chemosensory signal-transduction pathways.

PMID- 9140965
TI  - The CIT3 gene of Saccharomyces cerevisiae encodes a second mitochondrial isoform
      of citrate synthase.
AB  - We have identified a third citrate synthase gene in Saccharomyces cerevisiae
      which we have called CIT3. Complementation of a citrate synthase-deficient strain
      of Escherichia coli by lacZ::CIT3 gene fusions demonstrated that the CIT3 gene
      encodes an active citrate synthase. The CIT3 gene seems to be regulated in the
      same way as CIT1, which encodes the mitochondrial isoform of citrate synthase.
      Deletion of the CIT3 gene in a delta cit1 background severely reduced growth on
      the respiratory substrate glycerol, whilst multiple copies of the CIT3 gene in a
      delta cit1 background significantly improved growth on acetate. In vitro import
      experiments showed that cit3p is transported into the mitochondria. Taken
      together, these data show that the CIT3 gene encodes a second mitochondrial
      isoform of citrate synthase.

PMID- 9140966
TI  - Surface proteins and a novel transcription factor regulate the expression of the
      S-layer gene in Thermus thermophilus HB8.
AB  - We have identified proteins that control the expression of slpA, the gene
      encoding the crystalline surface layer of Thermus thermophilus HB8. We cloned
      three genes from T. thermophilus that specifically repressed the expression of
      the slpA promoter in Escherichia coli. The proteins encoded by two of them (Rep6
      and Rep29) bound in vitro to the slpA promoter, while that from the third (Rep54)
      bound specifically to the 5'-untranslated region (5'UTR) of the slpA mRNA. Rep6
      protein was identified as a C-fragment from a Thermus cytoplasmic basic protein
      of 28 kDa, whose coding gene, slrA (for S-layer regulator), was characterized.
      Surprisingly, Rep29 was identified as a C-fragment of SlpM, an S-layer-like
      protein that is overexpressed in slpA mutants. Insertional inactivation of slrA
      and slpM demonstrated their in vivo function in the control of slpA
      transcription: SlrA acts as a repressor, and SlpM as an activator. Even more
      surprising was the identification of Rep54, the 5'UTR mRNA-binding protein, as a
      C-terminal fragment of the SlpA protein. This result, in addition to further in
      vivo evidence presented here, supports the existence of a translational
      autoregulation in slpA expression. The physiological meaning of overlapping
      transcriptional and translational controls of S-layer expression, and its
      relationships with other systems, are discussed.

PMID- 9140967
TI  - YopK of Yersinia pseudotuberculosis controls translocation of Yop effectors
      across the eukaryotic cell membrane.
AB  - Introduction of anti-host factors into eukaryotic cells by extracellular bacteria
      is a strategy evolved by several Gram-negative pathogens. In these pathogens, the
      transport of virulence proteins across the bacterial membranes is governed by
      closely related type III secretion systems. For pathogenic Yersinia, the protein
      transport across the eukaryotic cell membrane occurs by a polarized mechanism
      requiring two secreted proteins, YopB and YopD. YopB was recently shown to induce
      the formation of a pore in the eukaryotic cell membrane, and through this pore,
      translocation of Yop effectors is believed to occur (Hakansson et al., 1996b). We
      have previously shown that YopK of Yersinia pseudotuberculosis is required for
      the development of a systemic infection in mice. Here, we have analysed the role
      of YopK in the virulence process in more detail. A yopK-mutant strain was found
      to induce a more rapid YopE-mediated cytotoxic response in HeLa cells as well as
      in MDCK-1 cells compared to the wild-type strain. We found that this was the
      result of a cell-contact-dependent increase in translocation of YopE into HeLa
      cells. In contrast, overexpression of YopK resulted in impaired translocation. In
      addition, we found that YopK also influenced the YopB-dependent lytic effect on
      sheep erythrocytes as well as on HeLa cells. A yopK-mutant strain showed a higher
      lytic activity and the induced pore was larger compared to the corresponding wild
      type strain, whereas a strain overexpressing YopK reduced the lytic activity and
      the apparent pore size was smaller. The secreted YopK protein was found not to be
      translocated but, similar to YopB, localized to cell-associated bacteria during
      infection of HeLa cells. Based on these results, we propose a model where YopK
      controls the translocation of Yop effectors into eukaryotic cells.

PMID- 9140968
TI  - Three disparately regulated genes for sigma 32-like transcription factors in
      Bradyrhizobium japonicum.
AB  - Bradyrhizobium japonicum possesses a subclass of heat-shock genes whose members
      are transcribed from a sigma 32 consensus promoter. Having identified previously
      one gene (rpoH1) encoding a sigma 32-like RNA polymerase transcription factor, we
      report here the characterization of two additional rpoH-like genes (rpoH2 and
      rpoH3). B. japonicum thus represents the first example of an organism possessing
      an rpoH multigene family. All three rpoH genes encode functional proteins that
      are able to initiate transcription from the Escherichia coli groE promoter. Each
      rpoH gene is apparently regulated by a different mechanism. Although both rpoH1
      and rpoH2 are transcribed from sigma 70-type promoters, transcription of the
      rpoH1 operon was found to be heat inducible by an unknown mechanism, whereas the
      level of rpoH2 mRNA decreased after heat shock. At extreme temperatures (48
      degrees C), rpoH2 was transcribed from a second promoter that resembled the E.
      coli sigma E-type promoter. The rpoH3 gene was found to be associated with two
      upstream genes, ragA and ragB, coding for a classical two-component regulatory
      system. Transcription initiated from a promoter that mapped in front of the
      putative response regulator gene ragA, suggesting that ragA, ragB and rpoH3 are
      organized in an operon. The ragA promoter was similar to a sigma 32 consensus
      promoter. The three B. japonicum rpoH genes also varied in their significance to
      support growth of the organism. While the rpoH2 gene could not be eliminated by
      mutation, knock-out mutants of rpoH1 and/ or rpoH3 were readily obtained and
      shown to be indistinguishable from the wild type under aerobic growth conditions
      or during root-nodule symbiosis. We conclude that rpoH2 is essential for the
      synthesis of cellular proteins under physiological growth conditions, whereas
      rpoH1, and probably also rpoH3, are involved in their synthesis during the stress
      response.

PMID- 9140969
TI  - The gene encoding the major proline transporter of Aspergillus nidulans is
      upregulated during conidiospore germination and in response to proline induction
      and amino acid starvation.
AB  - In Aspergillus nidulans a highly specific L-proline transporter is encoded by the
      prnB gene which is tightly linked to all other genes involved in proline
      catabolism. In mycelia, the expression of the prn structural genes is finely co
      regulated in response to proline induction and nitrogen/carbon catabolite
      repression. In this study we establish that prnB expression is also activated
      during germination of conidiospores. This activation persists until the
      development of 6 h-old mycelia and it is independent of proline induction
      mediated by the pathway-specific prnA gene product. We then show that, in
      mycelia, prnB transcription is activated in response to proline or histidine
      starvation. This process has two components: a prnA-dependent and a prnA
      independent component. A cis-acting element that conforms to the consensus target
      of the GCN4/CPC1 transcriptional activators mediating amino acid biosynthesis
      activation in other fungi is involved in the activation of prnB transcription in
      response to amino acid starvation. We also show that the stimulation of prnB
      expression in germinating conidiospores is not due exclusively to transient
      internal amino acid starvation occurring during the transition from conidiospore
      to mycelium. This is the first report that an amino acid transporter gene is
      upregulated during development and in response to amino acid starvation and
      specific amino acid induction.

PMID- 9140970
TI  - The HypB protein from Bradyrhizobium japonicum can store nickel and is required
      for the nickel-dependent transcriptional regulation of hydrogenase.
AB  - The HypB protein from Bradyrhizobium japonicum is a metal-binding GTPase required
      for hydrogenase expression. In-frame mutagenesis of hypB resulted in strains that
      were partially or completely deficient in hydrogenase expression, depending on
      the degree of disruption of the gene. Complete deletion of the gene yielded a
      strain (JH delta Eg) which lacked hydrogenase activity under all conditions
      tested, including the situation as bacteroids from soybean nodules. Mutant strain
      JH delta 23H lacking only the N-terminal histidine-rich region (38 amino acids
      deleted, 23 of which are His residues) expressed partial hydrogenase activity.
      The activity of strain JH delta 23H was low in comparison to the wild type in 10
      50 nM nickel levels, but could be cured to nearly wild-type levels by including
      50 microM nickel during the derepression incubation. Studies on strains
      harbouring the hup promoter-lacZ fusion plasmid showed that the complete deletion
      of hypB nearly abolished hup promoter activity, whereas the histidine deletion
      mutant had 60% of the wild-type promoter activity in 50 microM NiCl2. Further
      evidence that HypB is required for hup promoter-binding activity was obtained
      from gel-shift assays. HypB could not be detected by immunoblotting when the
      cells were cultured heterotrophically, but when there was a switch to
      microaerobic conditions (1% partial pressure O2, 10% partial pressure H2) HypB
      was detected, and its expression preceded hydrogenase synthesis by 3-6 h. 63Ni
      accumulation by whole cells showed that both of the mutant strains accumulate
      less nickel than the wild-type strain at all time points tested during the
      derepression incubation. Wild-type cultures that received nickel during the HypB
      expression-specific period and were then washed and derepressed for hydrogenase
      without nickel had activities comparable to those cells that were derepressed for
      hydrogenase with nickel for the entire time period. In contrast to the wild type,
      strain JH delta 23H cultures supplied with nickel only during the HypB expression
      period achieved hydrogenase activities that were 30% of those cultures supplied
      with nickel for the entire hydrogenase derepression period. These results
      indicate that the loss of the metal-binding area of HypB causes a decrease in the
      ability of the cells to sequester and store nickel for later use in one or more
      hydrogenase expression steps.

PMID- 9140971
TI  - Analysis of ssb mutations in vivo implicates SSB protein in two distinct pathways
      of SOS induction and in recombinational DNA repair.
AB  - Site-directed mutations in the Escherichia coli ssb gene were tested for the
      ability to complement a chromosomal ssb deletion for viability, and only the ssb
      W54-->G mutation failed to do so at the pSC101 copy level. Non-aromatic amino
      acid substitutions for SSB Trp-54 (ssb W54-->L and ssb W54-->S) produced the
      greatest effects on in vivo protein function including altered marker linkage
      subsequent to generalized transduction, extreme UV sensitivity, and a lack of
      ability to support SOS induction. Additionally, the ssb-113 (ssb P176-->S)
      mutation demonstrated the existence of both uvrA-dependent and uvrA-independent
      components of SOS induction. Although nucleotide excision repair appeared
      unaffected by alterations in the SSB protein, the mutational analysis suggests a
      direct role for SSB in recombinational repair.

PMID- 9140972
TI  - Mycobacterial recA is cotranscribed with a potential regulatory gene called recX.
AB  - The recA gene of Mycobacterium smegmatis has been cloned and sequenced. The amino
      acid sequence of the RecA protein is highly homologous to other RecA proteins.
      Three other potential open reading frames were identified. One of these showed
      extensive homology to a protein, HypB, involved in the incorporation of nickel
      into hydrogenases. Another, found downstream of and overlapping recA, was similar
      to a gene, recX, which has been proposed to play a regulatory role related to
      recA function. The homology between the M. smegmatis sequence and that of
      Mycobacterium tuberculosis extended upstream of the recA coding region for 140 bp
      including a motif identical to the Cheo-box consensus sequence which has been
      shown to bind LexA. In addition, the transcriptional start sites were found to be
      identical to those identified previously for M. tuberculosis. Transcriptional
      fusions to the reporter gene chloramphenicol acetyltransferase (CAT) revealed
      that recA was DNA-damage inducible and that expression required sequences at some
      distance from the mapped transcriptional start sites. Although a motif with only
      one mismatch to the Cheo box was found in the intergenic region between orf1 and
      orf2 these open reading frames were not DNA-damage inducible, nor was this motif
      required for regulation of recA expression. Gel retardation assays revealed that
      the reason for this was that LexA did not bind to this sequence containing a
      mismatch. Reverse transcription/polymerase chain reaction analysis of M.
      smegmatis RNA demonstrated that recA and orf3 (recX) are within the same
      transcriptional unit.

PMID- 9140973
TI  - Functional analysis of ssaJ and the ssaK/U operon, 13 genes encoding components
      of the type III secretion apparatus of Salmonella Pathogenicity Island 2.
AB  - We have investigated the structure and transcriptional organization of 13 genes
      of Salmonella Pathogenicity Island 2 (SPI2) that encode components of the second
      type III secretion apparatus of Salmonella typhimurium. ssaK, L, M, V, N, O, P,
      Q, R, S, T, U constitute one operon of 10 kb. ssaJ lles upstream of ssaK and is
      the terminal gene of another operon. The deduced products of ssaJ, ssaK, ssaV,
      ssaN, ssaO, ssaQ, ssaR, ssaS, ssaT, and ssaU show greatest similarity to the
      Yersinia spp. genes yscJ, yscL, lcrD, yscN, yscO, yscQ, yscR, yscS, yscT, and
      yscU, respectively. The products of the ssaL, ssaM and ssaP genes do not have
      significant similarity to products of other type III secretion systems, and might
      be important for the specific function of the SPI2 type III secretion system.
      Bacterial strains carrying different ssa mutations display minor alterations in
      terms of serum sensitivity when compared with the wild-type strain, but none are
      defective in replication within macrophage-like RAW 264.7 cells. However, some of
      the ssa mutant strains invade HEp2 cells less efficiently and are less cytotoxic
      to RAW 264.7 macrophages than the wild-type strain. We show that the invasion
      defect is correlated with a lack of SipC in culture supernatants of these mutant
      strains. SipC is a product of the SPI1 type III secretion system of S.
      typhimurium, and is important for epithelial cell invasion. Therefore, mutations
      in SPI2 can affect the SPI1 secretion system, which raises the possibility of an
      interaction between the two type III secretion systems.

PMID- 9140974
TI  - Cloning and functional characterization of Neisseria gonorrhoeae tonB, exbB and
      exbD genes.
AB  - Neisseria gonorrhoeae is able to utilize iron (Fe) from a variety of sources
      including transferrin (TF) and lactoferrin (LF). To gain insight into the
      molecular mechanisms used by gonococci to scavenge Fe from TF and LF, we cloned a
      3.5 kb segment of wild-type DNA that repaired the defect in tlu mutants, which
      are unable to take up Fe from either TF or LF despite exhibiting apparently
      normal ligand binding to the receptor. Nucleotide sequence determination
      identified three open reading frames (ORFs), designated ORF1, ORF2, and ORF3,
      which were arranged in tandem. The deduced amino acid sequence of the 852 bp ORF1
      encoded a 28 kDa protein that exhibited 26-32% identity with TonB proteins of
      nine other bacteria. The 663 bp ORF2 predicted a 24 kDa protein and the 435 bp
      long ORF3 predicted a 15 kDa protein. These predicted protein sequences exhibited
      32-38% and 24-36% identity, respectively, with ExbB and ExbD proteins of three
      other bacteria. Thus, the sequence comparison identified the ORF1, ORF2 and ORF3
      as gonococcal homologues of the E. coli tonB, exbB and exbD genes. An insertional
      mutation in the tonB homologue resulted in the failure of gonococci to grow with
      TF, LF or human haemoglobin (HB) as sole Fe sources and in the inability to take
      up 55Fe from TF and LF. The tonB mutation did not prevent the utilization of Fe
      from citrate (CT) or haemin (HM). Binding of TF, LF and HB to whole cells in a
      solid-phase binding assay was largely unaffected by the tonB mutation. We
      conclude that the pathways for utilization of Fe bound to TF, LF and HB but not
      to HM or CT were dependent on the TonB system.

PMID- 9140975
TI  - HIP1 propagates in cyanobacterial DNA via nucleotide substitutions but promotes
      excision at similar frequencies in Escherichia coli and Synechococcus PCC 7942.
AB  - The sequence 5'-GCGATCGC-3', designated HIP1, for highly iterated palindrome, was
      first identified at the borders of a gene-deletion event and subsequently shown
      to constitute up to 2.5% of the DNA in some cyanobacteria. It is now reported
      that HIP1 is polyphyletic, occurring in several distinct cyanobacterial lineages
      and not defining a clade. HIP1 does not introduce gaps into sequence alignments.
      It aligns with partial HIP1 sites in related sequences showing that it propagates
      by nucleotide substitutions rather than insertion. Constructs have been created
      to determine the frequencies at which deletion events occur between palindromes
      located within the selectable marker neo. Deletion between HIP1 sites was more
      frequent in Synechococcus PCC 7942 than deletion between control palindromes, 5'
      CCGATCGG-3', designated PAL0. However, this is not due to a recombinase that
      recognises HIP1 and is peculiar to cyanobacteria because similar deletion
      frequencies were detected in Escherichia coli. Furthermore, the frequency of
      deletion of DNA flanked asymmetrically by one HIP1 site and one PAL0 site was
      less than the frequency of deletion of DNA flanked asymmetrically by identical
      copies of either palindrome. This is consistent with deletion by copy-choice.

PMID- 9140976
TI  - Analysis of the interaction between the bacterial superantigen streptococcal
      pyrogenic exotoxin A (SpeA) and the human T-cell receptor.
AB  - Streptococcus pyogenes that produces the bacterial superantigen streptococcal
      pyrogenic exotoxin A (SpeA) is associated with outbreaks of streptococcal toxic
      shock syndrome (STSS) in the United States and Europe. SpeA stimulates V beta
      2.1, 12.2, 14.1, and 15.1-positive T cells, and the lymphokine production from
      the activated T cells is believed to result in the symptoms associated with STSS.
      The T-cell receptor (TCR)-SpeA interaction is crucial for superantigenic
      activity, and studies were undertaken to determine regions of both SpeA and the
      TCR involved in the formation of MHC/SpeA/TCR complexes. Previously, recombinant
      toxins encoded by speA alleles 1, 2, and 3 as well as toxins resulting from 19
      distinct point mutations in speA1 were generated. Here, these 22 toxin forms were
      incubated with human peripheral blood mononuclear cells (PBMCs), and the
      percentages of T-cell blasts bearing V beta chains 2.1, 12.2, and 14.1 were
      quantified by flow cytometry. The analysis indicates that the residues of SpeA
      needed for a productive TCR interaction differ for each V beta chain examined. An
      amino acid substitution at only one site significantly affected the toxin's
      ability to stimulate V beta 2.1-expressing T cells, three individual amino acid
      substitutions resulted in significant loss of ability to stimulate V beta 12.2
      expressing T cells, and substitution at 13 individual sites significantly
      affected the ability to stimulate V beta 14.1-expressing T cells. To elucidate
      the regions of the V beta chains that interacted with SpeA, synthetic peptides
      representative of the human V beta 12.2 complementary-determining regions (CDRs)
      1, 2, and 4 were used to block the SpeA-mediated proliferation of human PBMCs.
      The CDR1, CDR2 and CDR4 peptides were each able to block proliferation, with the
      activity of CDR1 > CDR2 > CDR4. Combinations of CDR1 peptide with CDR2 or CDR4
      peptides allosterically enhanced the ability of each to block proliferation,
      suggesting SpeA has distinct binding sites for the CDR loops.

PMID- 9140977
TI  - Molecular characterization of the Aspergillus nidulans treA gene encoding an acid
      trehalase required for growth on trehalose.
AB  - Aspergillus nidulans conidiospores contain high levels of the non-reducing
      disaccharide trehalose. We show that upon induction of conidiospore germination,
      the trehalose pool is rapidly degraded and a glycerol pool is transiently
      accumulated. A trehalase with an acidic pH optimum was purified from
      conidiospores. Characterization of the treA gene encoding this trehalase shows
      that it is homologous to Saccharomyces cerevisiae vacuolar acid trehalase, the
      product of the ATH1 gene, and to two related proteins of unknown function
      identified in Mycobacterium tuberculosis and Mycobacterium leprae. A. nidulans
      mutants that lack acid trehalase activity were constructed by gene replacement at
      the treA locus. Analysis of these mutants suggests that the treA gene product is
      localized in the conidiospore wall, is required for growth on trehalose as a
      carbon source, and is not involved in the mobilization of the intracellular pool
      of trehalose. Therefore, it is proposed that a cytoplasmic regulatory trehalase
      is controlling this latter process.

PMID- 9140978
TI  - Chlamydia psittaci IncA is phosphorylated by the host cell and is exposed on the
      cytoplasmic face of the developing inclusion.
AB  - Chlamydiae are obligate intracellular bacteria that replicate within a non
      acidified vacuole called an inclusion. Chlamydia psittaci (strain GPIC) produces
      a 39 kDa protein (IncA) that is localized to the inclusion membrane. While IncA
      is present as a single 39 kDa species in purified reticulate bodies, two
      additional higher M(r) forms are found in C. psittaci-infected cells. This
      finding suggested that IncA may be post-translationally modified in the host
      cell. Here we present evidence that IncA is a serine/threonine phosphoprotein
      that is phosphorylated by host cell enzymes. This conclusion is supported by the
      following experimental findings: (i) treatment of infected cells with inhibitors
      of host cell phosphatases or kinases altered the electrophoretic migration
      pattern of IncA; (ii) treatment with calf intestinal alkaline phosphatase
      eliminated the multiple-banding pattern of IncA, leaving only the protein band
      with the lowest relative molecular weight; and (iii) radioimmunoprecipitation of
      lysates of [32P]-orthophosphate-labelled infected HeLa cells with anti-IncA
      antisera demonstrated that the two highest M(r) IncA bands were phosphorylated. A
      vaccinia-virus recombinant expressing incA was used to determine if HeLa cells
      can phosphorylate IncA in the absence of a chlamydial background. IncA in lysates
      of these cells migrated identically to that seen in C. psittaci-infected cells,
      indicating the host cell was responsible for the phosphorylation of the protein.
      Microinjection of fluorescently labelled anti-IncA antibodies into C. psittaci
      infected HeLa cells resulted in immunostaining of the outer face of the inclusion
      membrane. Collectively, these results demonstrate that IncA is phosphorylated by
      the host cell, and regions of IncA are exposed at the cytoplasmic face of the
      inclusion.

PMID- 9140979
TI  - HatA and HatR, implicated in the uptake of inorganic carbon in Synechocystis
      PCC6803, contain WD40 domains.

PMID- 9140980
TI  - HatA and HatR, implicated in the regulation of inorganic carbon uptake process in
      Synechocystis PCC6803, may contain WD domains.

PMID- 9140981
TI  - A glutamate uptake regulatory protein (Grp) in Escherichia coli?

PMID- 9140982
TI  - A view of type I and II Na+/P(i) transporters through microelectrodes.

PMID- 9140983
TI  - Are angiotensin II receptor blockers superior to angiotensin converting enzyme
      inhibitors with regard to their renoprotective effect?

PMID- 9140984
TI  - Sodium-hydrogen antiporter: its possible role in the genesis of diabetic
      nephropathy.
AB  - The epidemiological evidence that only a subset of diabetic patients are
      susceptible to renal damage and the demonstration of clear familiar clustering of
      diabetic nephropathy are consistent with the possibility that genetic factors may
      explain the liability to or protection from renal disease of diabetic patients. A
      predisposition to hypertension and cardiovascular disease may be an important
      determinant of susceptibility to renal disease and its cardiovascular
      complications in diabetes since raised blood pressure [1] and an increased
      frequency of cardiovascular disease [2] are more prevalent in parents of diabetic
      patients with nephropathy. These results have raised growing interest in the
      search for intermediate phenotypes significantly associated with diabetic
      nephropathy, poorly influenced by environment, stable with age, easy to quantify
      and possibly dependent upon a single major gene effect. Such intermediate
      phenotypes can be useful for early diagnosis and would help clarify the molecular
      mechanisms leading to diabetic nephropathy. An elevation of Na+/H+ antiporter
      activity has consistently been associated with diabetic renal disease both in
      insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes
      mellitus (NIDDM) patients, making this cell membrane exchanger system an ideal
      intermediate phenotype for the study of diabetic nephropathy.

PMID- 9140986
TI  - Minimal invasive in vivo pharmacology: news of a new method holding promise in
      nephrology-related research.

PMID- 9140985
TI  - Anti-GBM antibodies in Goodpasture syndrome; anatomy of an epitope.

PMID- 9140989
TI  - The impact of vascular access for haemodialysis on patient morbidity and
      mortality.

PMID- 9140987
TI  - Co-trimoxazole and Wegener's granulomatosis: more than a coincidence?

PMID- 9140988
TI  - Does dialysis-related amyloidosis regress after transplantation?

PMID- 9140990
TI  - Bone biopsy--beyond light microscopy and histodynamics.

PMID- 9140991
TI  - Pathogenesis of diabetic nephropathy: a radical approach.

PMID- 9140993
TI  - Sleep-related breathing disturbances: their pathogenesis and potential interest
      to the nephrologist.
AB  - For about 120 years we have been looking for the 'cause' of essential
      hypertension. It is possible that we have merely been wandering through its
      graveyard, looking at the pathogenetic mechanisms but never the actual cause?
      Here we pass the gravestone of increased sympathetic activity; there the
      gravestone of low renin activity. Here high endothelin; there low EDRF. Here high
      thromboxane A2; there low prostacyclin. It is possible that all these and so many
      other pathogenetic factors are all due to one basic defect? Is it possible that,
      in the dead of night while patients with EH have been sleeping, the villain has
      been lurking in their mouths, stuck somewhere at the back of their throats,
      hidden from view yet choking them hundreds of times a night. But this
      intermittent strangulation has not occurred silently. On the contrary, it has
      made its presence felt in the most irritating way, with snores, groans, grunts,
      gasps and frightening periods of total apnea. But we, their physicians, never
      asked about these symptoms, or, if we did, we never paid heed to them. This is
      clear from the fact that, most cases of OSA occur in association with EH yet are
      not diagnosed. Perhaps the next 'arousal response' should be the arousal of
      physicians' consciousness so that they can at long last wake up to the existence
      of the close connection between sleep-related breathing disorders and
      hypertension and breathe some new life into the treatment of two old diseases
      essential hypertension and secondary hypertension. Early diagnosis and treatment
      of the sleep-related breathing disorders may not only make the patient feel much
      better, (something our antihypertensive medications do not always do), but may
      reduce the blood pressure and prevent the progression of renal and cardiovascular
      damage as well.

PMID- 9140992
TI  - TGF-beta and glomerulonephritis: anti-inflammatory versus prosclerotic actions.
AB  - TGF-beta has been considered as the key regulator in the generation of
      glomerulosclerosis. Despite abundant descriptive data, it still remains
      undetermined whether sustained, local expression of TGF-beta leads to
      irreversible glomerulosclerosis. There is no doubt that TGF-beta stimulates ECM
      production in the glomerulus, but this molecule has several anti-inflammatory
      properties as well. Towards a better understanding of the pathogenesis of
      glomerulonephritis and for the development of novel and efficient therapeutic
      interventions, extensive efforts should be made to clarify the 'bright side' of
      TGF-beta as well as its 'dark side' in individual experimental and human
      diseases, focusing especially on the concentration and the time-point at which
      its anti-inflammatory properties spill over into its prosclerotic actions.

PMID- 9140994
TI  - Nephrology and renal replacement therapy in Romania.
AB  - BACKGROUND: In the context of the transformation of the Health Systems of Central
      and Eastern European countries, the role of professional associations is
      increasing, especially as regards data collection, analysis, and implementation
      of programmes for development of nephrology and renal replacement therapy (RRT).
      METHODS: The Romanian Renal Registry sent questionnaires to the heads of
      Haemodialysis and Nephrology Centres. The need for renal replacement therapy was
      deduced from the annual incidence (127 patients p.m.p.) of chronic renal failure.
      RESULTS: Although the rates of increase in the numbers of Nephrology Departments
      (+82%), HD Centres (+142%), and total number of patients alive on RRT (+196%)
      from 1991 to 1995 were higher than the European mean, only 27-30% of the incident
      patients (459 of 1000-1200 patients) could be provided with RRT. Sixty-two
      percent of the need for RRT in the age group 25-44 years was met, while only 20%
      of children (age < 15 years) and people over 55 years requiring RRT received this
      treatment. Primary renal diseases in patients on RRT were glomerulonephritis
      (49%) or interstitial nephropathies (23%); diabetic nephropathies,
      nephroangiosclerosis and systemic diseases were rare (4, 2, and 1% respectively).
      Most of the CRF patients (88%) were treated by HD. Renal transplantation and
      peritoneal dialysis were seldom performed (8 and 4%). The cost of HD treatment in
      Romania (87 USD) is low, even though dialyser reuse is not common practice.
      CONCLUSIONS: The increase in renal replacement therapy in Romania was mainly due
      to the expansion of the number of haemodialysis centres. Although a significant
      progress was realized, only one-third of the patients needing RRT could be
      treated in Romania in 1995.

PMID- 9140995
TI  - Preliminary evidence for a role of apolipoprotein E alleles in identifying
      haemodialysis patients at high vascular risk.
AB  - Conventional risk factors have very low predictive power in identifying
      haemodialysis patients at high risk of vascular accidents. A role for
      apolipoprotein E isotypes was looked for in a small, but rigorously defined,
      cohort of longterm haemodialysis patients. In individuals with high vascular
      risk, as identified by higher common carotid intima/media thickness, we found an
      excess of apolipoprotein E4 alleles. This preliminary result requires
      confirmation in large patient cohorts.

PMID- 9140996
TI  - Angiotensin II requires PDGF-BB to induce DNA synthesis in rat mesangial cells
      cultured in an exogenous insulin-free medium.
AB  - BACKGROUND: Mesangial cell proliferation is an important feature of chronic
      glomerular disease. Different cytokines and vasoactive substances have been
      implicated in mesangial cell proliferation. However, the role of angiotensin II
      remains controversial. Furthermore, all the studies made to date have been
      performed using a medium supplemented with high concentrations of insulin (5
      micrograms/ml) in order to facilitate mesangial cell proliferation in vitro. As
      has recently been reported, insulin causes a change both in extracellular matrix
      composition and in mesangial cell phenotype, thus mimicking disease conditions.
      METHODS: We examined the effects of Ang II in synchronized and proliferating
      mesangial cells with and without growth factor (PDGF-BB, bFGF and/or insulin)
      supplementation and the effects of exogenous administration of insulin on
      mesangial proliferation by measuring the bromodeoxyuridine (BrdU) uptake.
      RESULTS: Angiotensin II itself caused no increase in BrdU incorporation. However,
      it exerted a significant synergistic effect on PDGF-BB-induced DNA synthesis (P <
      0.05) in quiescent medium and tended to stimulate BrdU uptake by proliferating
      cells (P = 0.09). BrdU incorporation significantly correlated with direct cell
      count (r = 0.95). PDGF-BB had the maximal stimulatory effect on DNA synthesis
      both in quiescent and in proliferative culture conditions. The insulin dose (5
      micrograms/ml) which has been shown to cause mesangial cell proliferation in
      vitro, caused an increase in BrdU incorporation by itself in quiescent medium.
      CONCLUSIONS: We conclude that in an insulin-free medium, mimicking in vivo
      glomerular conditions, PDGF-BB or proliferative medium are needed to allow Ang II
      induced DNA synthesis in mesangial cell culture.

PMID- 9140997
TI  - Leucocyte beta 1,3 galactosyltransferase activity in IgA nephropathy.
AB  - BACKGROUND: Reduced galactosylation of the O-linked glycans of the IgA1 hinge
      region in IgAN has recently been described. To investigate the underlying defect
      resulting in this abnormality, we have measured the activity of beta 1,3
      galactosyltransferase, the enzyme responsible for galactosylation of O-linked
      sugars. METHODS: A galactose-acceptor substrate was prepared from
      degalactosylated hinge region fragments of normal IgA1, and incubated with the T
      cell, B cell, and monocyte lysates from patients with IgAN and controls for
      acceptor regalactosylation. The extent of acceptor galactosylation was then
      measured with biotinylated Vicia villosa lectin (VV), which is specific for
      ungalactosylated moieties. Lectin binding of serum IgA from the same subjects was
      also measured. RESULTS: T cell and monocyte beta 1,3 galactosyltransferase
      activities did not differ between IgAN and control, but B cell lysates in IgAN
      showed significantly lower beta 1,3 galactosyltransferase activity than control
      (6.2 +/- 0.71 vs. 9.5 +/- 1.03 AU/microgram, P = 0.018). Furthermore, B cell beta
      1,3 galactosyltransferase activity showed a negative correlation (r = -0.87, P =
      0.002) with VV lectin binding of serum IgA in IgAN, but not controls.
      CONCLUSIONS: These data indicate that altered IgA1 O-galactosylation in IgAN
      results from a B cell-restricted reduction of beta 1,3 galactosyltransferase
      activity. This enzyme defect may be a fundamental pathogenic abnormality in IgAN.

PMID- 9140998
TI  - Different erythrocyte and platelet surface electric charge in various types of
      glomerulonephritis.
AB  - BACKGROUND: Some preliminary observations suggest that predisposition to a
      particular type of glomerulonephritis (GN) may be connected with the genetically
      determined charge of the glomerular capillary wall. A correlation between
      erythrocyte surface and the glomerular capillary wall charges has also been
      observed. The purpose of this study was to verify and extend previous
      investigations. Therefore we measured erythrocyte and platelet surface charge
      from patients with idiopathic membranous and mesangial GN as well as idiopathic
      membranoproliferative GN and lupus nephritis. METHODS: The erythrocyte and
      platelet surface charge was determined by the binding of the cationic dye, alcian
      blue (AB). A fresh alcoholic AB solution was made for each experiment, which were
      run in batches of four, each including cells from a healthy person and from
      patients each with a different type of GN. RESULTS: In patients with idiopathic
      membranous and membranoproliferative GN, a significant decrease in the
      erythrocyte and platelet charges was observed irrespective of their clinical
      state (remission or nephrotic syndrome). Erythrocyte charge was decreased despite
      the normal amount of membranous sialic acid. In contrast, patients with
      idiopathic mesangial GN, in complete or partial remission, exhibited normal
      erythrocyte and platelet surface charges. Exclusively in this type of GN, the
      appearance of nephrotic proteinuria was associated with a slight decrease, the
      erythrocyte charge, which was not statistically significant (P > 0.1). A
      reduction in the negative erythrocyte charge in lupus nephritis was less in
      magnitude than in idiopathic membranous or membranoproliferative GN, and occurred
      independently of the level of daily proteinuria, whereas the platelet charge was
      normal. CONCLUSION: The decrease of the erythrocyte and platelet charge in
      idiopathic membranous and mebranoproliferative GN seems to be a pre-morbid
      feature.

PMID- 9140999
TI  - Thiobarbituric acid reactive substances are increased in the subcutaneous fat
      tissue of patients with end-stage renal disease.
AB  - BACKGROUND: Patients with end-stage renal disease are thought to be in a highly
      peroxidative state, based on studies showing decreased serum antioxidant activity
      and increased peroxidative products. In this study we confirm these findings by
      examining lipid peroxidation in subcutaneous fat tissue in uraemia. SUBJECTS AND
      METHODS: Twenty-seven subcutaneous fat samples were taken from patients with end
      stage renal disease when they underwent intervention for arteriovenous fistula
      for haemodialyis or for catheter insertion for continuous ambulatory peritoneal
      dialysis. The control samples were taken from 11 patients with normal renal
      function and without any history of renal disease who had surgical interventions.
      Lipid peroxides were measured as thiobarbituric acid reactive substance. RESULTS:
      The concentration of thiobarbituric acid reactive substances in subcutaneous fat
      tissue in the patients with end-stage renal disease is 1.223 +/- 0.636 nmol/mg
      fat tissue (mean +/- SD) whereas the level in the control group is 0.097 +/-
      0.054 nmol/mg fat tissue. A comparison of the two groups by Student's t test
      revealed a highly significant difference (P < 0.001). CONCLUSIONS: This study
      supports the finding of a severe peroxidative state in patients with end-stage
      renal disease.

PMID- 9141000
TI  - Onset of coronary artery disease prior to initiation of haemodialysis in patients
      with end-stage renal disease.
AB  - To determine whether the onset of coronary artery disease may precede the
      initiation of dialysis in patients with end-stage renal disease, we performed
      coronary angiography within 1 month of initiation of maintenance haemodialysis in
      24 patients (age range 42-78 years; mean 63.7 +/- 11). Coronary angiography was
      performed regardless of the absence or presence of angina. Fifteen patients had
      diabetic nephropathy, and nine had non-diabetic nephropathy. Significant coronary
      stenosis was defined as at least 75% narrowing of the reference segment. Fifteen
      patients (62.5%) with a total of 49 lesions were classified as the coronary
      artery disease present group. Eleven of those 15 (73.3%) had multivessel disease.
      The average number of stenotic lesions was 3.3 per patient. The most common
      patterns of stenosis were complex (23 lesions; 47%), and diffuse lesions over 20
      mm long (14 lesions; 29%). None of the clinical or haematological factors
      evaluated differed significantly between the groups with and without coronary
      artery disease. The prevalence of coronary artery disease was 72.7% in the
      symptomatic patients and 53.8% in the asymptomatic patients. The diagnosis of
      coronary artery disease at the start of maintenance haemodialysis based only on
      chest symptoms and clinical factors proved to be difficult. Coronary angiography
      is thus essential for evaluating coronary artery disease in uraemic patients.
      Many patients with end-stage renal disease had coronary artery disease prior to
      the start of haemodialysis.

PMID- 9141001
TI  - Left ventricular hypertrophy and ambulatory blood pressure monitoring in chronic
      renal failure.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) is both common and an important
      predictor of risk of death in end-stage renal failure (ESRF). In mild to moderate
      chronic renal failure (CRF), the timing of onset of LVH and the factors involved
      in its initial development have not been fully elucidated. The present study was
      undertaken to examine the prevalence and potential determinants of
      echocardiographically determined LVH in this connection, and to compare 24-h
      ambulatory blood pressure (BP) recordings with BP measured at a previous clinic
      visit. METHODS: From a cohort of 120 non-diabetic patients who had been attending
      a nephrology clinic, 118 agreed to participate in the study. Of these we selected
      for analysis 85 stable patients (37 male). Patients with known cardiovascular
      disease, those with a history of poor compliance with antihypertensive
      medication, and those in whom such medication had been changed in the previous 3
      months were excluded. Clinic BP, 24-h ambulatory BP, echocardiography, body mass
      index (BMI), serum creatinine (SCr), creatinine clearance (CrCl), haemoglobin
      (Hb), fasting cholesterol (CHOL), triglyceride TRIGL), plasma glucose, calcium
      (Ca), phosphate (PO4), alkaline phosphatase (ALK PHOS), parathyroid hormone (PTH)
      concentrations, and 24-h urinary protein were assessed in all patients. Seventy
      seven per cent were on antihypertensive medication. RESULTS: LVH was detected in
      16% of patients with CrCL > 30 ml/min, and 38% of patients with CrCl < 30 ml/min.
      By stepwise regression analysis, ambulatory systolic BP (P < 0.0001), male gender
      (P < 0.0001), BMI (P < 0.0002), and Hb concentration (P < 0.002) were the only
      independent determinants of left ventricular (LV) mass. Nocturnal systolic BP (P
      < 0.02) was the main determinant of LVH in the group of patients with advanced
      CRF. The correlation between left ventricular mass index (LVMI) and mean 24-h
      ambulatory systolic BP (r = 0.52, 95% confidence interval 0.50-0.54) was
      statistically significantly stronger than with outpatient systolic BP (r = 0.25,
      95% confidence interval 0.23-0.27). The same was true for the correlation between
      LVMI and mean 24-h ambulatory diastolic BP (r = 0.42, 95% confidence interval
      0.40-0.44), and outpatient diastolic BP (r = 0.22, 95% confidence interval 0.20
      0.24). CONCLUSIONS: Twenty-four hour ambulatory BP recording and echocardiography
      are required for accurate diagnosis of inadequate BP control and early LVH in
      patients with chronic renal impairment, independent determinants of which are
      hypertension, male sex, BMI, and anaemia.

PMID- 9141002
TI  - Effects of recombinant interleukin-2 and revaccination for hepatitis B in
      previously vaccinated, non-responder, chronic uraemic patients. Collaborative
      Group of Girona.
AB  - BACKGROUND: Growing evidence suggests that it is possible to seroconvert chronic
      renal failure patients who are absolute non-responders to hepatitis B vaccine by
      means of either additional booster vaccine doses or associated IL-2
      administration or both. We have studied the possibilities of hepatitis B
      seroconversion by revaccination and its dependence on vaccine dose, and the
      effects of a concurrent low-dose rHuIL-2 regime. METHODS: Forty known absolute
      non-responders with chronic renal failure were entered into a complete
      revaccination protocol. Patients were randomly assigned to two dosage groups of
      either 20 or 40 micrograms hepatitis B vaccine administered at 0, 1, 2 and 6
      months. Further randomly selected patients from each dosage group were given
      500,000 U of rHuIL-2 in the same deltoid area 4 h after vaccine administration.
      RESULTS: Sixty-seven per cent of patients revaccinated with 40 micrograms
      attained antibody protecting levels compared to only 20% of those receiving doses
      of 20 micrograms (P < 0.025). When compared with initial values, the ThCD4/CD25
      cell count was significantly reduced immediately after HuR-IL2 administration (P
      < 0.003) and significantly increased 1 month after the last dose was given (P <
      0.0003). A definite rHuIL-2 effect on HBV antibody synthesis could not be
      demonstrated, nor was erythropoietin found to enhance seroconversion.
      CONCLUSIONS: From these results we suggest that more intense and frequent
      antigenic stimulation as obtained by revaccination using four doses of 40
      micrograms may effectively reduce the pool of hepatitis B vaccine nonresponders
      in chronic renal failure patients.

PMID- 9141003
TI  - Orthostatic hypoxaemia in dialysed adult polycystic kidney disease patients.
AB  - BACKGROUND: Recently we observed a unique clinical phenomenon, namely,
      orthostatic or postural hypoxaemia in a 72-year-old female adult polycystic
      kidney disease (APKD) patient, maintained on CAPD. Extensive investigations
      failed to yield a satisfactory explanation for her ambulatory hypoxaemia.
      METHODS: To validate our observation, 15 dialysed patients underwent blood gases
      analyses in both the supine and ambulatory positions (SpO2 and ApO2
      respectively). Patients were divided into two groups: group 1 (n-7) whose end
      stage renal failure (ESRF) was due to APKD and group 2 (n-8) in whom ESRF was due
      to other causes. Both haemodialysed (HD) and CAPD patients were included. ApO2
      was determined as the pO2 immediately upon standing up. Readings in HD patients
      were taken at the end of the dialysis session, that is, at the patients' dry
      weight. RESULTS: Respective SpO2 and ApO2 of the two groups were 85 +/- 17.1 and
      78 +/- 20.5 vs 85.8 +/- 19 and 91 +/- 21 mmHg. Delta change in pO2 defined as the
      mean decrease (negative value) or mean increase (positive value) of ApO2 in
      relation to SpO2 was -7.85 (group 1) vs + 5.2 mmHg (group 2), P < 0.005. In group
      1, six of seven patients demonstrated a negative delta. In group 2, four of eight
      showed a positive delta whilst the remaining four had no change in the delta
      value. CONCLUSION: Orthostatic hypoxaemia may occur in dialysed patients whose
      ESRF is due to APKD.

PMID- 9141004
TI  - Incidence and risk factors of hepatitis C virus infection in a haemodialysis
      unit.
AB  - BACKGROUND: Hepatitis viruses have become one of the main infectious problems in
      patients on maintenance haemodialysis. The aim of this study was to prospectively
      investigate the incidence of de novo hepatitis C virus (HCV) infection in a
      haemodialysis unit and to identify factors currently involved in HCV transmission
      to haemodialysis patients. METHODS: One hundred and fourteen anti-HCV negative
      and HCV-RNA negative patients who started long-term haemodialysis were followed
      for a mean period of 36 months (range 18-56). Liver tests and anti-HCV were
      performed at 6-month intervals. Factors that might be implicated in HCV
      transmission, such as blood transfusions, sexual habits, surgery and other
      invasive procedures, were recorded. HCV markers were re-examined in transfused
      blood and the HCV genotype was investigated in seroconverters to anti-HCV and in
      patients with previous HCV infection who were treated in the vicinity of those
      who seroconverted. RESULTS: Eight patients (7%) seroconverted to anti-HCV and
      seven of them became HCV-RNA positive. HCV markers, including HCV-RNA, were
      negative in the blood transfused to seroconverters. No differences between
      seroconverters and non-seroconverters. No differences found in other risk factors
      not directly related to haemodialysis. The investigation of HCV genotype
      suggested that HCV transmission was not restricted to patients treated in the
      vicinity of previously HCV infected patients. Occasional failure to observe
      strict measures of asepsis was detected in the haemodialysis unit and this was
      the only factor that might be incriminating. CONCLUSIONS: HCV acquisition in
      patients on haemodialysis is currently not related to blood transfusion, and
      nosocomial transmission within the haemodialysis unit seems to be the main
      mechanism of HCV infection. Extremely careful observation of preventive measures
      seems essential to eradicate HCV transmission in haemodialysis units.

PMID- 9141005
TI  - Erythropoietin and sexual dysfunction.
AB  - BACKGROUND: Erythropoietin (rHuEpo) therapy has been shown to improve sexual
      function in the male dialysis population, with several studies suggesting a
      direct effect upon endocrine function, as well as correction of anaemia.
      Nevertheless many male dialysis patients receiving rHuEpo continue to complain of
      sexual dysfunction. METHODS: At a dedicated renal impotence clinic, 65 male
      dialysis patients were screened for endocrine disturbances. Baseline serum sex
      hormones were compared between those receiving and not receiving rHuEpo, using
      either the two-sample t test or the Mann-Whitney U test, after assessing for
      normality. Results from four patients were excluded on account of either
      medications (antiemetic phenothiazines), hepatic dysfunction, or carcinomatosis.
      RESULTS: Twenty-five patients (41.0%) were receiving rHuEpo, the recipients and
      non-recipients being well matched for haemoglobin (10.19 +/- 0.29 vs 10.55 +/-
      0.25 g/dl, n.s.), age (51.1 +/- 1.9 vs 53.6 +/- 2.1 years, n.s.) and duration of
      sexual dysfunction (median, 3.0 vs 3.0 years, n.s.). The rHuEpo recipients had a
      higher median creatinine (1090 vs 972 micromol/l, P < 0.02), but similar
      nutritional status to the non-recipients (albumin 41.0 vs 39.0 g/l, n.s.). The
      total duration of rHuEpo therapy was 0.85 +/- 0.14 years. Prolactin levels were
      similar in both the rHuEpo recipients and non-recipients (440 vs 541 mu/l, n.s.),
      as were LH (11.0 vs 10.5 iu/l, n.s.) and FSH (8.0 vs 6.5 iu/l, n.s.). However,
      there were significant elevations of testosterone (19.8 +/- 1.3 vs 16.1 +/- 1.1
      nmol/l, P < 0.05) and sex hormone binding globulin (SHBG) (40.5 vs 26.0 nmol/l, P
      < 0.01), with a trend toward elevated oestradiol (304 vs 248 pmol/l, P = 0.095)
      in the rHuEpo-treated group. Forty-eight subjects (78.7%) received peritoneal
      dialysis (PD), with the 19 rHuEpo recipients (39.6%) demonstrating increased
      serum testosterone (21.0 +/- 1.5 vs 16.6 +/- 1.3 nmol/l, P < 0.05), SHBG (40.5 vs
      26.5 nmol/l, P < 0.01), LH (15.0 vs 10.0 iu/l, P < 0.01) and FSH (12.0 vs 5.3
      iu/l, P < 0.05). These differences were not demonstrated in the 13 haemodialysis
      (HD) subjects. CONCLUSIONS: Male dialysis patients complaining of sexual
      dysfunction after correction of anaemia with rHuEpo are characterized by higher
      levels of serum testosterone and SHBG, but not suppression of hyperprolactinaemia
      or hyperoestrogenism. Male PD subjects receiving rHuEpo also demonstrated
      increased LH and FSH.

PMID- 9141006
TI  - The long-acting dopamine agonist bromocriptine mesylate as additive
      immunosuppressive drug after kidney transplantation.
AB  - BACKGROUND: Acute rejection is an important risk factor for kidney graft loss. As
      evidence suggests that prolactin has important immunostimulatory properties, we
      conducted a randomized, prospective open trial in which bromocriptine, a drug
      suppressing prolactin secretion, was administered as an additive
      immunosuppressive drug after first cadaver kidney transplantation. METHODS: In
      the treatment group bromocriptine was given intramuscularly to 22 patients after
      their first kidney transplantation along with conventional immunosuppression
      (cyclosporin A, glucocorticoids). Twenty-three patients receiving only
      conventional immunosuppression served as control subjects. The incidence of acute
      graft rejections, graft losses, and infections was evaluated. RESULTS: Serum
      prolactin concentrations were slightly elevated above normal values before
      transplantation (32 +/- 5.3 ng/ml) and decreased to values between 13 and 16
      ng/ml in the control group and were totally suppressed in the bromocriptine
      group. After 6 months of follow-up overall patient and allograft survival was
      97.7% and 91% respectively. Acute rejection episodes occurred in 31 patients
      (77.5%): 15 in the bromocriptine group vs 20 in the control group (n.s.). In each
      group eight patients experienced a cytomegalovirus infection. The incidence of
      severe bacterial infections (i.e. pneumonia and sepsis) was five and six
      respectively. The necessity of haemodialysis after transplantation was 3.1% in
      the patients on bromocriptine and 23% in those without. CONCLUSIONS: Suppression
      of circulating prolactin concentration by bromocriptine did not improve the
      clinical outcome of patients after kidney transplantation receiving cyclosporin
      and prednisolone.

PMID- 9141007
TI  - Interleukin-6 expression after renal transplantation.
AB  - BACKGROUND: Interleukin-6 (IL-6) is an inflammatory cytokine that plays a role in
      transplant rejection. We tested the hypothesis that IL-6 levels in serum or urine
      could be of value in predicting acute and chronic allograft rejection.
      Furthermore, we examined whether or not such levels reflected IL-6 expression in
      the kidney. METHODS: We measured IL-6 and IL-6 soluble receptor (IL-6sR) in serum
      and urine of 145 transplant patients and 20 normal controls. In parallel, we
      studied 108 renal biopsies. IL-6 was measured with a bioassay system using an IL
      6 dependent cell line. IL-6sR was measured with enzyme-linked immunosorbent
      assay. The biopsies were examined for IL-6 and IL-6 receptor (IL-6R) expression
      with immunohistochemistry. RESULTS: Rejection episodes occurring within 2 months
      of transplantation were accompanied by elevated IL-6 concentrations in serum (17
      +/- 4.8 pg/ml, P < 0.05) and urine (114 +/- 27 pg/ml, P < 0.005), compared to
      controls. These values returned towards baseline (0-5 pg/ml) after successful
      rejection treatment. The sensitivity of urine measurements was much higher (93%)
      than serum (54%). The specificity in serum (70%) and urine (60%) was reduced by
      infection, acute tubular necrosis, and antithymocyte globulin treatment. Serum
      and urine IL-6sR values did not correlate with rejection. In biopsy tissue, IL-6
      and IL-6R were both elevated during rejection. Especially, mononuclear cells
      within the interstitial infiltrate stained positive. However, the amount of IL-6
      positive cells did not correlate with peripheral IL-6 concentrations.
      CONCLUSIONS: Urine but not serum IL-6 values are sensitive indicators of
      rejection; however, they are confounded by infection, acute tubular necrosis, and
      certain antirejection treatments. These features limit their usefulness.

PMID- 9141008
TI  - Prednisone dosage and pregnancy outcome in renal allograft recipients.
AB  - BACKGROUND: The literature contains reports of 2309 pregnancies in some 1600
      women who have undergone renal transplantation. Certain pre-pregnancy factors,
      especially hypertension, renal graft dysfunction, short interval between
      transplant and pregnancy, and high immunosuppressive drug dosage, appear to
      increase the neonatal risks. METHOD: We describe the outcome of 42 pregnancies in
      27 allograft recipients at Rabin Medical Center (Beilinson Campus) in Israel
      during the last 8 years. All were treated with combination immunosuppression
      regimens. RESULTS: The average interval from transplantation to conception was
      3.7 +/- 0.4 years (2 months to 9 years). Rejection episodes occurred in 37% prior
      to pregnancy but in none during or immediately after pregnancy. Twenty-eight
      percent of the pregnancies ended in therapeutic or spontaneous abortions, and 29
      of the 30 deliveries ended in a live birth. The prematurity rate (63%) was
      similar to that described in the literature for this patient group. Renal
      deterioration was evident in seven women (26%) within 2 years after delivery. Use
      of 7.5 mg/d prednisone (vs. 10 mg/d) before pregnancy was observed as the most
      significant preconception parameter related to better pregnancy outcome. A long
      interval from transplantation to conception and lack of pre-existing hypertension
      were also significant. CONCLUSION: The better pregnancy outcome associated with
      lower prednisone dosage is probably related to the fact that the patients
      selected to receive the low-dose regimen have had a longer and less complicated
      post-transplantation course.

PMID- 9141009
TI  - Infectious disease complications of simultaneous pancreas kidney transplantation.
AB  - BACKGROUND: Although technical success rate of simultaneous pancreas kidney (SPK)
      transplantation in insulin-dependent diabetes mellitus (IDDM) patients with
      diabetic nephropathy has improved, morbidity remains high due to infection and
      rejection. The purpose of this study was to analyse infections encountered in our
      series of SPK transplants, using a restrictive antibiotic prophylaxis policy.
      METHODS: We reviewed all infectious diseases after 66 consecutive bladder-drained
      SPK transplantations in 64 IDDM patients with end-stage renal disease due to
      diabetic nephropathy. During follow-up, the perioperative antibiotic regimen was
      altered (from 5 days preemptive therapy with multiple drugs to 1 day prophylaxis
      with cefamandole), and long-term viral prophylaxis (high-dose aciclovir) was
      introduced. For post-operative urinary tract or opportunistic infection, no
      prophylaxis was given. RESULTS: Overall mean infection rate was 2.9 infections/
      patient/year after a mean follow-up of 2.3 years. Surgical site infections (SSI)
      were seen in 30% of the patients, with Enterococci present in 47%. Logistic
      regression showed one day cefamandole prophylaxis to be associated with SSI, but
      there was no significant influence of SSI on either graft or patient survival.
      Forty-eight percent of all infections were lower urinary tract infections (UTI).
      There were 59 first UTIs (89%), probably related to long-term Foley catheter use,
      and 47 second UTIs (71%). Subsequent UTIs were not microbiologically related to
      first UTIs. Cytomegalovirus (10 patients) and other opportunistic agents did not
      cause mortality or graft loss. Five grafts were lost due to infection (SSI three
      times, post-transplant lymphoproliferative disease twice). Only one patient died
      because of infection (2%). CONCLUSIONS: Infectious diseases after SPK
      transplantation caused significant morbidity but did not influence either patient
      or graft survival. A change in prophylactic policy for both SSI as well as
      recurrent UTI, combined with earlier Foley removal, may lower incidences of these
      infections.

PMID- 9141011
TI  - Alport syndrome and diffuse leiomyomatosis with major morbid events presenting at
      adult age.

PMID- 9141010
TI  - Indwelling silicone femoral catheters: experience of three haemodialysis centres.
AB  - The aim of this study is to describe the experience of three haemodialysis
      centres using indwelling femoral silicone catheter (model SSL 1220M, Medcomp,
      USA) in 55 patients, three with acute renal failure, one requiring
      plasmapheresis, and 51 with chronic renal failure but no other available vascular
      access. Sixty-four catheters were in place for a mean duration of 41.5 +/- 30
      days. The rate of catheter-related complications, including mechanical problems,
      thromboses, and infections was low and they were never life-threatening. The
      results of the study suggest that femoral cannulation with modern flexible
      devices can be considered as a reliable temporary access, even for extended
      periods, with advantages exceeding those for subclavian and jugular routes.

PMID- 9141012
TI  - Idiopathic acute interstitial nephritis and uveitis associated with deafness.

PMID- 9141013
TI  - Crescentic glomerulonephritis with antineutrophil cytoplasmic antibodies
      associated with chronic lymphocytic leukaemia.

PMID- 9141014
TI  - A child with panniculitis and microhaematuria/proteinuria--an unusual
      presentation of p-ANCA-positive vasculitis.

PMID- 9141015
TI  - Severe nephrotic syndrome in a patient with Schonlein-Henoch purpura: complete
      remission after cyclosporin A.

PMID- 9141016
TI  - Severe and prolonged jaundice in a lupus nephritis patient treated with
      cyclophosphamide.

PMID- 9141017
TI  - Renal artery embolization after back massage in a patient with aortic occlusion.

PMID- 9141018
TI  - Non-oliguric acute renal failure associated with hepatitis E.

PMID- 9141019
TI  - Enteric hyperoxaluria and renal failure associated with lymphangiectasia.

PMID- 9141020
TI  - Calcific atrial mass in end-stage renal failure.

PMID- 9141022
TI  - Hypertensive crises following platelet transfusions in a patient on
      erythropoietin therapy.

PMID- 9141021
TI  - Cat-scratch disease in a patient undergoing haemodialysis.

PMID- 9141023
TI  - Inadvertent placement of a Tenckhoff catheter into the urinary bladder.

PMID- 9141024
TI  - Relapsing CAPD peritonitis with rapid peritoneal sclerosis due to Haemophilus
      influenzae.

PMID- 9141025
TI  - Peritransplant lymphocele causing arterial hypertension by a Page kidney
      phenomenon. Leuven Collaborative Group for Transplantation.

PMID- 9141026
TI  - Acquired vein stenosis of renal allograft--percutaneous treatment with self
      expanding metallic stent.

PMID- 9141027
TI  - Infected transplant pancreatic pseudocyst managed by catheter drainage and
      pancreatico-ileostomy.

PMID- 9141028
TI  - Xanthogranulomatous pyelonephritis in the native kidney of a renal transplant
      recipient.

PMID- 9141029
TI  - An unusual case of villous adenoma of the ampulla Vateri in a renal allograft
      recipient.

PMID- 9141030
TI  - Grim projections for American nephrologists.

PMID- 9141031
TI  - ANCA-positive Churg-Strauss syndrome with renal failure.

PMID- 9141032
TI  - ANCA-positive rapidly progressive glomerulonephritis: there may be more to the
      diagnosis than you think!

PMID- 9141033
TI  - Spinal abscess with cord compression complicating infected subclavian cannula.

PMID- 9141034
TI  - The young girl with renovascular hypertension of unknown origin.

PMID- 9141035
TI  - 6th Verona Seminar on Nephrology, Verona, Italy, September 19-21, 1996.
AB  - The Veronese biennial meeting aimes to provide an up-to-date overview on topics
      of recent interest and progress. In 1996 the Scientific Committee devised a
      programme which spent the spectrum from basic science to very practical clinical
      problems.

PMID- 9141036
TI  - Survival in haemodialysis: is there a role for vascular access?

PMID- 9141037
TI  - Follow-up on a transplant recipient with chromomycosis.

PMID- 9141038
TI  - Herpes simplex virus as a sentinel lesion for cytomegalovirus infection.

PMID- 9141039
TI  - Recombinant human erythropoietin (epoetin) and autologous blood transfusion in
      chronic haemodialysed patients: two observations.

PMID- 9141040
TI  - Influence of overweight on survival of kidney transplant.

PMID- 9141041
TI  - The effect of dialysis membrane on serum beta 2-microglobulin (beta 2M) in
      chronic haemodialysis patients.

PMID- 9141042
TI  - Neurobiological basis of motor learning in mammals.
AB  - Long-term potentiation (LTP) has been proposed as a model of learning and memory.
      There is still little evidence, however, linking LTP to cognitive processes. We
      have chosen to study motor learning, first, because it is relatively simpler than
      cognitive learning and second, because much of the circuitry involved in motor
      function is already known. In behavioral studies we determined that the sensory
      cortex is required for the acquisition of new motor skills. Once a skill is
      acquired, however, the sensory cortex is no longer necessary in the performance
      of that skill. In electrophysiological experiments we have shown that LTP can be
      induced in the motor cortex with stimulation of the sensory cortex (SCx) or
      associativly when stimulation was applied to both SCx and thalamus. We propose
      that motor learning involves the formation of loop circuits between the motor
      cortex and the periphery involving the SCx and the thalamus. At first these loop
      circuits are diffuse, producing contraction of unnecessary muscles, but become
      specific by producing LTP through practice.

PMID- 9141043
TI  - The progressive tactile hyperalgesia induced by peripheral inflammation is nerve
      growth factor dependent.
AB  - Experimental peripheral inflammation results in cutaneous mechanical
      hypersensitivity, and repeated low intensity mechanical stimulation of the
      inflamed skin induces a progressively incrementing hyperalgesia. We have now
      examined whether the elevation in nerve growth factor (NGF) induced by the
      inflammation contributes to this progressive hyperalgesia. An i.p. injection of
      anti-NGF antiserum (5 microliters g-1) 1 h before induction of inflammation by
      intraplantar complete Freund's adjuvant (CFA) injection and 24 h after, both
      reduced the basal inflammatory hypersensitivity and significantly attenuated the
      progressive increase of spontaneous activity, touch-, pinch- and A beta-afferent
      evoked responses, and the progressive reduction of the mechanical threshold of
      biceps femoris/semitendinosus alpha motoneurones normally evoked by repeated
      (every 5 min) tactile stimulation of the inflamed hindpaw, in decerebrate-spinal
      rats. NGF contributes, therefore, to the progressive tactile hyperalgesia
      elicited by repeated touch stimulation of inflamed tissue.

PMID- 9141044
TI  - Effects of deoxycorticosterone acetate and diazepam on neuropeptidergic neurons
      in rat striatum.
AB  - The neurosteroid tetrahydrodeoxycorticosterone (THDOC) interacts with gamma
      aminobutyric acid (GABA)/ benzodiazepine (BZ) receptors. To test the hypothesis
      that THDOC works partially through mechanisms associated with GABAA/BZ receptor
      function, deoxycorticosterone acetate (DOCA) and the benzodiazepine, diazepam
      (DZ), were administered short- (1 day) and long-term (11 days). Levels of mRNA
      for dynorphin, preprotachykinin and preproenkephalin in the striatum of adult
      male Sprague-Dawley rats were measured by in situ hybridization. Acute DOCA and
      DZ treatment produced parallel neuropeptide mRNA profiles, whereas chronic DOCA
      and DZ treatment yielded different patterns of neuropeptide gene expression.
      Chronic DZ treatment resulted in no significant increase in salt intake whereas
      chronic DOCA activated salt appetite. We suggest that acute DZ and DOCA interact
      with GABAA/BZ receptors; however, the results of chronic treatment suggest that
      DZ and DOCA operate through dissimilar mechanisms.

PMID- 9141045
TI  - Parturition upregulates nitric oxide synthase activity in the rat anterior
      pituitary gland.
AB  - Recent evidence suggests that endogenous nitric oxide (NO) contributes to the
      modulation of hormonal secretion from the anterior pituitary gland according to
      the physiological state of the animal. In this study, nicotinamide adenine
      dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and specific
      neurochemical assay were used to asses possible changes of NO synthase (NOS)
      activity in the anterior pituitary during pregnancy and parturition in rats. The
      anterior pituitary showed (weak) NADPH-d activity throughout pregnancy.
      Parturition increased the number and intensity of NADPH-d-positive cells. The
      NADPH-d-positive cells co-localized with immunofluorescent LH-positive cells. No
      variation in NADPH-d activity was apparent during the various stages of the
      oestrous cycle. Furthermore, NOS activity during parturition increased
      significantly when compared with non-pregnant and pregnant rats. Increases in
      both specific activity and NADPH-d activity gradually decreased within 24 h post
      partum, suggesting that NO may modulate anterior pituitary function during
      parturition.

PMID- 9141046
TI  - Dendritic compartmentation of NMDA receptor mRNA in cultured hippocampal neurons.
AB  - The intracellular localization of mRNA encoding the obligatory subunit for the N
      methyl-D-aspartate (NMDA) receptor complex (NMDAR1) was determined in cultured
      hippocampal neurons by in situ hybridization. From the time at which dendrites
      begin to develop, labeling for NMDAR1 mRNA extended beyond cell somata into
      incipient dendritic processes. By 10 days in culture, label was found throughout
      dendritic arbors in a distribution pattern similar to that for microtublin
      associated proteins 2 mRNA, but contrasted sharply with that for GluR1 or beta
      actin mRNAs, both of which were restricted to cell somata. NMDAR1 mRNA was also
      expressed in astrocytes, where it was diffusely localized throughout the
      cytoplasm. These data suggest that transport of NMDAR1 mRNA may serve as a
      mechanism to target and manipulate local concentrations of NMDA receptors.

PMID- 9141048
TI  - Motion templates with eye velocity gain fields for transformation of retinal to
      head centric flow.
AB  - Heading perception from the optic flow is more difficult during eye rotations
      than when the eye is stationary, because the centre of the retinal motion
      identifies the fixation direction rather than the direction of heading. Eye
      movement signals helps when motion parallax is absent. This paper distinguishes
      two different possibilities for interactions between eye movement and visual
      motion signals to perceive heading with a rotating eye. A pre-motion template
      transformation changes local retinal velocity into head centric velocity. These
      velocities then feed head centric motion templates. A post-motion template model
      combines oculomotor signals with retinal motion templates to arrive at head
      centric flow templates. The latter scheme involves eye velocity gain fields
      similar to the eye position gain fields as found in area 7a. We propose that the
      parietal cortex transforms retinal to head centric direction and retinal to head
      centric flow on the same principle.

PMID- 9141047
TI  - Levels of stimulatory G protein are increased in the rat striatum after neonatal
      lesion of dopamine neurons.
AB  - After neonatal lesions of dopamine neurones, an enhanced behavioural
      responsiveness towards D1 agonists has been described, suggesting a D1 receptor
      hypersensitivity. In the present study, unilateral striatal dopamine denervation
      in newborn rats induced a pronounced rotational behaviour following apomorphine
      injection at the adult age, without any change in the density of D1 binding sites
      in the denervated striatum. The amount of stimulatory G(olf) alpha subunit was
      increased by 35% in the lesioned striatum. The large form and the short forms of
      Gs alpha were also increased by 26% and 9%, respectively. Since in striatal
      neurones, the coupling of D1 receptor to adenylate cyclase is mostly provided by
      G(olf) alpha, our results strongly suggest that D1 hypersensitivity described
      after neonatal dopamine lesions results from an increase in the levels of G(olf)
      alpha protein.

PMID- 9141049
TI  - Spatial memory in transgenic mice with impaired glucocorticoid receptor function.
AB  - Spatial learning and memory function of transgenic mice with impaired
      glucocorticoid receptor function was assessed in the Morris water maze and the
      radial arm maze. Transgenic mice took longer to find a submerged and a visual
      platform in the water maze task than did mice from the parent strain (B6C/3F1),
      although performance was improved in the visible platform condition relative to
      the submerged platform task. In the radial arm maze, transgenic mice made
      significantly more errors than B6C/3F1 mice. In both tasks, the behavioural
      strategies adopted by transgenic mice were non-optimal for correct performance.
      It is suggested that the impaired performance displayed by transgenic mice in
      both tests is largely attributable to these altered behavioural strategies.

PMID- 9141050
TI  - Induction of ischemic tolerance and antioxidant activity by brief focal ischemia.
AB  - Three forms of non-injurious ischemic preconditioning were tested for their
      effects on endogenous antioxidant activity and subsequent ischemic injury. Test
      ischemia alone, consisting of 1 h occlusion of both carotid arteries (BCAs) and
      one middle cerebral artery (MCA), elicited an average volume of cerebral
      infarction of 143.4 +/- 15.0 mm3 (mean +/- s.e.m.). Twenty minutes occlusion of
      the MCA only or MCA and BCAs (but not BCAs only) 24 h before test ischemia
      significantly increased the activity of the antioxidant enzyme superoxide
      dismutase and significantly reduced the cerebral infarction volume. These
      findings demonstrate that brief focal ischemia can attenuate the injurious impact
      of subsequent ischemia and that an upregulation of endogenous antioxidant
      activity may play a key role in this neuroprotective effect.

PMID- 9141052
TI  - Visual working memory for shape and 3D-orientation: a PET study.
AB  - In order to determine the neural substrate of working memory for shape and 3D
      orientation, regional cerebral blood flow (rCBF) changes were estimated using
      positron emission tomography (PET). Subjects were scanned during the performance
      of two delayed-matching-to-sample tasks using flat polydedrical objects of
      different shapes and 3D-orientations presented in a virtual environment. The
      shape matching task was associated with activation in the occipito-temporal
      junction, occipito-parietal cortex and mesial frontal pole of the right
      hemisphere. During the orientation matching task, rCBF increased in the mesial
      occipito-temporal cortex, superior temporal gyrus and middle frontal gyrus of the
      left hemisphere. The right supramarginal gyrus was also activated. These results
      suggest that both visual pathways are engaged in the processing of objects
      presented in different orientations. The dorsal stream is involved mainly in
      working memory of 3D-orientation, while the ventral stream is involved especially
      in shape working memory.

PMID- 9141051
TI  - Effect of nilvadipine on high-voltage activated Ca2+ channels in rat CNS neurons.
AB  - The effect of nilvadipine, a dihydropyridine derivative, on high-voltage
      activated (HVA) Ca2+ channels was investigated in freshly dissociated rat frontal
      cortical neurons. The cortical neurons were observed to have five
      pharmacologically distinct HVA Ca2+ channel subtypes consisting of the L-, N-, P
      , O- and R-types. Nilvadipine selectively inhibited the L-type Ca2+ channel
      current which comprised 23% of the total HVA Ca2+ channel current. A reversible
      inhibitory effect of nilvadipine on the L-type Ca2+ channel current was also
      observed in a concentration-dependent fashion without affecting the current
      voltage relationship. The half-maximum inhibitory concentration was 3 x 10(-8) M.
      These results suggest that the inhibitory effect of nilvadipine on the neuronal
      Ca2+ influx, in combination with the cerebral vasodilatory action, may prevent
      neuronal damage during brain ischemia.

PMID- 9141053
TI  - An unusual effect of application of the amino acid L-arginine on cat visual
      cortical cells.
AB  - Iontophoretic application of L-arginine (L-Arg) resulted in a profound decrease
      in visually elicited and spontaneous activity in 22 of 77 (29%) cells in area 17
      of the anaesthetized/paralysed cat. Duration was long, and cells did not recover
      pre-application activity levels, indicating permanent decline. This effect was
      obtained without change in the extracellularly recorded wave-form, demonstrating
      that this did not result from depolarization block. In the remaining 55 cells,
      application of L-Arg alone, at levels capable of eliciting inhibition as
      described above, was without effect. In 29 cells, L-Arg application was able to
      reverse the effect of inhibition of nitric oxide (NO) production. Populations of
      cells showing the depressive effect described above and those affected by NO
      modulation levels were mutually exclusive.

PMID- 9141054
TI  - Apoptosis is restricted to the thalamus in thiamine-deficient rats.
AB  - Thiamine deficiency (TD) produces lesions in the thalamus, mamillary and medial
      geniculate nuclei, and inferior colliculus. To clarify the pathogenesis of these
      lesions, we examined the occurrence of hallmarks of apoptosis following TD in rat
      brain. Histological assessment showed apoptotic cells in the thalamus and medial
      geniculate nucleus but not in the inferior colliculus. We used terminal
      deoxynucleotidyl transferase-mediated deoxyuridine (dUPT)-biotin nick-end
      labelling (TUNEL) and gel electrophoresis to demonstrate that TD is associated
      with apoptotic cell death. In the thalamus, DNA fragmentation appeared from day
      14 of deficiency and preceded the appearance of ataxia. The inferior colliculus
      and mamillary nucleus were without electrophoretic DNA fragments, and only rare
      TUNEL-positive labelling was observed. This model shows a rare combination of
      both apoptosis and necrosis in the same lesioned brain.

PMID- 9141055
TI  - Visuospatial mnemonic load modulates event-related slow potentials.
AB  - Electroencephalographic slow wave potentials were recorded during the performance
      of visuospatial working memory tasks. The aim was to study the effects of varying
      mnemonic loads on slow potentials, and to dissociate the contribution of mnemonic
      and motor components. Subjects were tested with three spatial delayed matching-to
      sample tasks in which the mnemonic load varied while the preparatory motor
      demands remained constant. The delay-related slow potential was more negative
      during the tasks in which the subjects had to memorize the locations of six or
      four stimuli than when only one location had to be memorized. Significant
      differences between the slow potentials in the tasks with different mnemonic
      loads were recorded at frontal and temporal recording sites. Since the
      preparatory motor requirements were similar in all tasks, the modulation of slow
      potentials reflects working memory processing rather than motor preparatory
      activity.

PMID- 9141056
TI  - Effect of tolcapone on plasma and striatal apomorphine disposition in rats.
AB  - The influence of tolcapone, an inhibitor of catechol-O-methyl transferase, was
      evaluated on the disposition of apomorphine, a dopamine agonist used to treat
      Parkinson's disease, to explain a previously observed increase of duration of the
      effect of apomorphine associated with tolcapone. Sampling was performed in rats
      before and at different times after administration of apomorphine and following
      that of tolcapone or saline. Both in plasma and striatum, times to reach maximal
      concentration and maximal concentrations did not significantly differ between the
      two groups but the elimination half-life times and areas under the curve were
      significantly greater following tolcapone treatment than in the saline group.
      These results show that tolcapone can increase plasma apomorphine bioavailability
      by modifying its liver catabolism.

PMID- 9141057
TI  - Sex differences in nitrite/nitrate levels and antioxidant defense in rat brain.
AB  - This study assessed sex differences in stable metabolites of nitric oxide and
      major enzymes involved in antioxidant defense in various regions of rat brain.
      Nitrite/nitrate levels and activities of superoxide dismutase and catalase were
      determined in cortex, hippocampus, corpus striatum, midbrain and cerebellum of
      adult male and female Sprague-Dawley rats. Nitrite/nitrate levels were
      significantly higher in the cortex and the hippocampus of male than female rats,
      while catalase activity was higher in the cortex of females than in males. These
      sex differences may have significant effects on brain function in health and
      disease.

PMID- 9141058
TI  - Neuronal subpopulations in the suprachiasmatic nuclei based on their response to
      retinal and intergeniculate leaflet stimulation.
AB  - In order to characterize how suprachiasmatic nuclei (SCN) neurons integrate its
      visual inputs, extracellular responses from SCN and adjacent hypothalamic neurons
      were recorded after stimulation of either the retina, the intergeniculate leaflet
      (IGL) or both simultaneously. Individual stimulation of either structure elicited
      excitatory or inhibitory responses in 36% of SCN and 20% of non-SCN neurons.
      Three subpopulations of SCN neurons were found, the first two responding
      exclusively either to the retina or the IGL, and the third responding to both the
      retina and the IGL. Simultaneous stimulation of the retina and the IGL induced a
      change in the firing pattern of some SCN neurons, which suggests modulatory
      regulation of SCN neuronal activity by synaptic interactions between its visual
      inputs.

PMID- 9141059
TI  - Reduction of vesicular acetylcholine transporter mRNA in the rat septum following
      lead exposure.
AB  - We have previously observed that maternal exposure to lead (Pb) results in a
      reduction of levels of mRNA coding for cholineacetyltransferase (ChAT) in the
      septum of developing rat without affecting the dams. Here we report that Pb
      similarly affects the expression of vesicular acetylcholine transporter (VAChT)
      mRNA in the rat septum. In close agreement with the time course of ChAT mRNA
      expression, septal VAChT mRNA levels increased from 30% at postnatal day 7 to 78%
      and 100% of adult levels at days 14 and 21, respectively. Maternal exposure to
      0.2% lead acetate in drinking water from gestational day 16 resulted in an
      approximately 30% reduction of VAChT in 7 and 21-day-old rat pups without
      affecting VAChT mRNA levels in the dams. These results indicate a developmental
      stage-dependent interference by Pb with ChAT/VAChT gene expression in the rat
      septum.

PMID- 9141061
TI  - Deficient antisaccades in the social-emotional processing disorder.
AB  - We investigated whether adolescents and adults with the developmental social
      emotional processing disorder (SEPD) exhibit deficits in visual attention, as
      measured by eye movements, when compared with dyslexic and normal control
      subjects. On the antisaccade task, subjects with SEPD made more errors than
      either control group and were the only group to show a decrease in performance
      accuracy compared with prosaccade. This deficit in inhibiting reflexive shifts of
      attention and gaze suggests that individuals with SEPD have dysfunction of the
      prefrontal component of the right hemisphere dominant network for spatially
      directed attention.

PMID- 9141060
TI  - Blockade of joint inflammation and secondary hyperalgesia by L-NAME, a nitric
      oxide synthase inhibitor.
AB  - Acute arthritis is associated with pain-related behavior, joint swelling and
      increased joint temperature. Arthritic animals exhibit a significant decrease in
      paw withdrawal latency 4, 5, 6, 7 and 8 h after induction of inflammation, when
      compared with baseline values, indicative of secondary hyperalgesia. Intra
      articular injection of a non-specific nitric oxide synthase (NOS) inhibitor, NG
      nitro-L-arginine methyl ester hydrochloride (L-NAME), resulted in a complete
      reversal of heat hyperalgesia and prevented further increase in joint swelling
      and temperature, while injection of either isotonic saline or the inactive
      enantiomer NG-nitro-D-arginine methyl ester (D-NAME) after induction of arthritis
      had no effect on any of these parameters. Intra-articular injection of 7-nitro
      indazole (7-NINA), a selective neuronal NOS inhibitor, reversed the heat
      hyperalgesia for about 1 h but did not inhibit the increase in joint swelling or
      temperature. These results suggest an important role for nitric oxide (NO) in
      mediating peripheral nociceptive transmission and inflammation.

PMID- 9141062
TI  - Is amyloid beta-protein glycated in Alzheimer's disease?
AB  - Recent data suggest that protein glycation is involved in the process of amyloid
      formation in Alzheimer's disease (AD). To further investigate this issue, we
      analyzed the presence of advanced glycation end products (AGE) in soluble and
      insoluble forms of amyloid beta-protein (A beta) as well as in apolipoprotein E
      (apoE), a protein bound to amyloid deposits. Both proteins were extracted from
      cerebral cortex obtained from patients with AD and probed by immunoblotting with
      two antibodies specific for different AGE, already known to immunocytochemically
      label amyloid plaques. All the AGE antibodies failed to recognize either A beta
      or apoE, whereas they reacted with synthetic A beta glycated in vitro. These
      findings indicate that other proteins associated with amyloid deposits are
      candidates to be modified with AGE in Alzheimer's cerebral tissue.

PMID- 9141063
TI  - Auditory event-related potentials (ERP) reflect temporal changes in speech
      stimuli.
AB  - We studied the brain's reactions to deviations in the duration of a stop
      consonant using event-related potentials in an oddball paradigm. A naturally
      produced nonsense word was used as a frequent standard stimulus which differed
      from two infrequently presented deviant stimuli only by the duration of the
      silence period inside the stop, making the consonant sound longer. Evoked
      responses to the deviant stimuli showed sharply rising negativity after the
      unexpected prolongation of the silence and a later negativity, the duration of
      which was related to the timing of the beginning of the second part of the
      deviant sound. This later negativity is, at least partly, elicited by a mismatch
      process to the omission of a sound at the expected latency.

PMID- 9141064
TI  - Diurnal variation of TNF alpha in the rat brain.
AB  - Tumor necrosis factor-alpha (TNF alpha) is thought to play a physiological role
      in the brain. These studies were performed to determine whether a diurnal rhythm
      of TNF alpha exist in the rat brain. Samples were collected from hippocampus,
      hypothalamus, cerebral cortex, cerebellum, pons and midbrain at light onset and
      at 6 h intervals thereafter over a day. A TNF alpha bioassay was used to measure
      TNF alpha in each area. TNF alpha was highest at light onset in the hypothalamus,
      hippocampus and cerebral cortex. Levels at light onset were about 10-fold greater
      than minimal night-time levels. Changes in TNF alpha activity in other brain
      areas were also evident, but smaller. These results support the hypothesis that
      TNF alpha has physiological roles in the brain.

PMID- 9141065
TI  - Electrophysiological correlates of categorical phoneme perception in adults.
AB  - Event-related potentials, recorded through a 128-electrode net, were used to
      study phonemic processing in the human auditory system. Within a stream of
      identical syllables, acoustic deviants were introduced that either crossed a
      phonetic boundary or remained within the same category. Two phonetic boundaries
      were explored, one present and the other absent in the subjects' native language.
      A large mismatch negativity was induced by native phonetic deviants, but not by
      non-native or within-category deviants. We suggest that a language-specific
      phonemic code has a separate neural representation in sensory memory and can
      serve as the basis for auditory mismatch detection. The subjects' inability to
      discriminate non-native phonetic contrasts does not seem related to a late
      attentional filter, but rather to a genuine loss of auditory discrimination
      abilities.

PMID- 9141066
TI  - Localization of gamma-aminobutyric acid (GABA) receptor rho 3 subunit in rat
      retina.
AB  - We used digoxigenin-labelled single strand DNA probes to examine the expression
      of the mRNA encoding gamma-aminobutyric acid receptor rho 3 subunit in sections
      of the adult rat retina. Transcript for the rho 3 subunit was found in cell
      somata of a portion of cells lying in the ganglion cell layer.

PMID- 9141067
TI  - Effects of inactivation of the magnocellular preoptic nucleus of olfactory bulb
      processing.
AB  - The magnocellular nucleus (MCPO) was inactivated in anaesthetized rats, using
      muscimol, a gamma-amino butyric acid ergic agonist, in order to examine the
      effect of suppression of its tonic activity on extracellular unit firing in the
      granular (GRL), mitral (MCL) and external plexiform (EPL) layers of the olfactory
      bulb (OB). In GRL there was a significant increase in unit activity during the
      first hour after muscimol injection (30 ng), followed by a significant decrease
      in activity during the following hour. No effect on activity in MCL was seen
      after muscimol injection into the MCPO. Unit activity in EPL increased during the
      second hour post-injection. It was concluded that MCPO plays an important part in
      regulating the balance between granule and tufted cell activity.

PMID- 9141068
TI  - Receptor-induced beta gamma release from fatty acylation-deficient mutants of G
      alpha z.
AB  - The neuronal-specific G protein Gz is known to interact with a large variety of
      receptors for neurotransmitters and hormones. Fatty acylations on the N-terminus
      of the alpha subunit of Gz (alpha z) provide anchorage to the plasma membrane.
      Fatty acylation-deficient mutants of alpha z have previously been shown to
      exhibit altered signaling properties. Since the N-terminus of alpha z is likely
      to play a critical role in beta gamma binding, we examined the ability of these
      mutants to interact with beta gamma subunits by means of receptor-mediated
      stimulation of beta gamma-sensitive type II adenylyl cyclase. Our results
      indicate that lack of myristoylation, but not lack of palmitoylation, impaired
      the ability of alpha z to mediate receptor-induced release of beta gamma
      subunits.

PMID- 9141070
TI  - Effect of hypothermia on microglial reaction in ischemic brain.
AB  - Intra-ischemic hypothermia is known to protect neurons against ischemic injury.
      Microglial cells have been shown to become activated following ischemia and are
      speculated to play significant roles in the evolution of ischemic neuronal
      injury. In this study, we examined the effect of intra-ischemic hypothermia on
      the microglial reaction in the hippocampus following transient forebrain ischemia
      produced in gerbils by 10 min bilateral carotid occlusion at 30 degrees C or at
      37 degrees C, followed by normothermic reperfusion for 1-7 days. Microglial cells
      were visualized by histochemical staining with isolectin-B4 from Griffonia
      simplicifolia. Brains subjected to normothermic ischemia showed activation of
      microglia at 1 day post-ischemia; this increased with further recirculation,
      becoming intense by 3 days and diminished by 7 days. Ischemia under hypothermic
      conditions was not associated with activation of microglia, and these brains
      showed no significant neuronal damage, whereas the brains subjected to
      normothermic ischemia showed extensive neuronal necrosis in the CA1 region after
      1 and 7 days reperfusion. The presence of activated microglial cells in the CA1
      region prior to and in parallel with evolution of ischemic neuronal damage, the
      lack of such activation in brains subjected to the neuroprotective action of
      intra-ischemic hypothermia, together with the known potential capability of
      microglial cells to release cytotoxic substances appear to indicate that these
      cells could contribute significantly to ischemic neuronal necrosis.

PMID- 9141069
TI  - Peripheral NMDA and non-NMDA glutamate receptors contribute to nociceptive
      behaviors in the rat formalin test.
AB  - The present study demonstrates that local cutaneous administration of either the
      N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK-801 or the non-NMDA
      glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)
      significantly attenuates formalin-induced nociceptive behaviors. Specifically,
      pretreatment with either drug reduced the magnitude and time course of lifting
      and licking behavior in the late phase of formalin pain; however, flinching
      behavior was not affected. In contrast, post-treatment of formalin pain with
      either antagonist did not affect lifting and licking behavior, although flinching
      behavior was mildly attenuated. We hypothesize that these actions result from
      blocking of peripheral glutamate receptors located on unmyelinated axons at the
      dermal-epidermal junction. These data suggest that peripheral glutamate receptors
      on cutaneous axons can be manipulated to reduce certain aspects of pain of
      peripheral origin. This route of administration offers the advantage of avoiding
      the side effects of systemic administration.

PMID- 9141071
TI  - Oxytocin neurone autoexcitation during morphine withdrawal in anaesthetized rats.
AB  - We investigated whether release of oxytocin into the supraoptic nucleus is
      involved in morphine-withdrawal excitation of oxytocin neurones. Retrodialysis of
      naloxone into the supraoptic nucleus of morphine-dependent rats increased
      intranuclear oxytocin release by 56.5p +/- 12.7% whereas no change was seen in
      vehicle-treated dependent rats. In another experiment, in morphine-dependent rats
      given intravenous (i.v.) naloxone, intracerebroventricular (i.c.v.) oxytocin
      receptor antagonist injection reduced the increase of plasma oxytocin
      concentration (to 28-fold) compared with i.c.v. vehicle (62-fold increase).
      Finally, the increase in oxytocin neurone firing rate following morphine
      withdrawal in the presence of i.c.v. oxytocin antagonist infusion was 28% of the
      steady state firing rate (15-20 min later) and this was lower (p < 0.05) than the
      percentage increase in i.c.v. vehicle-infused rats (89%). Thus, central
      endogenous oxytocin may be involved in withdrawal excitation of oxytocin
      neurones.

PMID- 9141072
TI  - Brain potentials indicate differences between regular and irregular German
      plurals.
AB  - Event-related brain potentials were recorded as 18 German-speaking subjects read
      sentences that contained as critical words German nouns in correct and incorrect
      plural forms. Two types of plurals were investigated: regular -s plurals (e.g.
      Karussell-s 'roundabouts') and irregular -(e)n plurals (Muskel-n "muscles'). We
      compared correct regular and irregular plurals with incorrect ones; the latter
      had -(e)n on nouns that actually take -s plurals (*Karussell-en), or -s on nouns
      that require -(e)n (*Muskel-s). ERPs showed different responses to regular and
      irregular plurals: incorrect irregular plurals (*Muskel-s) elicited a ramp-shaped
      left frontotemporal negativity, whereas incorrect regulars (*Karussell-en)
      produced a central phasic negativity with a maximum at 380 ms. This dissociation
      supports the view that regularly inflected words are processed differently from
      irregularly inflected ones.

PMID- 9141073
TI  - Huperzine A, a potential therapeutic agent for dementia, reduces neuronal cell
      death caused by glutamate.
AB  - Huperzine a, a potential therapeutic agent for Alzheimer's disease, inhibits
      acetylcholinesterase in primary cultures derived from forebrain, hippocampus,
      cortex and cerebellum of embryonic rat brain. Glutamate induces cell death in
      cultures from all these brain regions. Maximum cell toxicity was observed in
      cerebellar cultures. Pretreatment of cell cultures with Huperzine A reduced cell
      toxicity, as evidenced by cytotoxicity assay and general morphology. Huperzine A
      pretreatment also reduced glutamate-induced calcium mobilization, but did not
      affect elevations in intraneuronal free Ca2+ ([Ca]i) caused by KCl or (-)Bay K
      8644. The data suggest that Huperzine A could be a potent neuroprotective agent
      not only where cholinergic neurons are impaired, but also under conditions in
      which glutamatergic functions are compromised.

PMID- 9141074
TI  - An immunocytochemical study of a G-protein-gated inward rectifier K+ channel
      (GIRK2) in the weaver mouse mesencephalon.
AB  - It has been suggested that a mutation in a G-protein-gated inward rectifier K+
      channel (GIRK2) is responsible for inducing cell death in the cerebellum of
      homozygous weaver (wv/wv) mutant mice. These mice also display a progressive,
      massive loss of mesencephalic dopaminergic neurones. Using an immunocytochemical
      method, we detected GIRK2-positive cell bodies and fibres in the substantia nigra
      pars compacta (SNC) and the ventral tegmental area (VTA) of control (+/+) mice.
      Cell counts of both GIRK2- and tyrosine hydroxylase (TH)-positive neurones
      demonstrated a marked loss of SNC cell bodies, especially in 12-month-old (12M)
      wv/wv mice. A considerable proportion of GIRK2-positive cell bodies were
      preserved, however. In addition, no loss of GIRK2-positive neurones was observed
      in the VTA of 12M wv/wv mice, despite of a significant reduction in TH-positive
      cell bodies. These results suggest that expression of the mutated channel is not
      a sufficient condition to induce cell death in the ventral mesencephalon of the
      wv/wv mice.

PMID- 9141075
TI  - Absence of neurotoxicity of chronic L-DOPA in 6-hydroxydopamine-lesioned rats.
AB  - We investigated the effects of 6 months' oral treatment with L-dihydroxy
      phenylalanine (L-DOPA)/carbidopa on the remaining dopaminergic neurones of the
      substantia nigra pars compacta (SNC) and the ventral tegmental area (VTA) of rats
      with moderate or severe 6-hydroxydopamine (6-OHDA)-induced lesions and sham
      operated animals. Using a radioimmunohistochemical method we counted tyrosine
      hydroxylase (TH)-radioimmunoreactive cells in the SNC and the VTA in emulsion
      coated sections and measured the remaining surface area of both structures on
      autoradiograms. The sole difference observed was a significant increase of the
      remaining surface area of TH radioimmunolabelling in the SNC of moderately
      lesioned rats treated with L-DOPA/carbidopa compared with the untreated animals,
      while the rest of the parameters recorded, in both structures and groups of
      animals, were unchanged. This suggest that in vivo, this treatment is not toxic
      either to healthy dopaminergic neurones of the ventral mesencephalon or to those
      surviving after a 6-OHDA lesion.

PMID- 9141076
TI  - Concomitant induction of apoptosis and necrosis in cerebellar granule cells
      following serum and potassium withdrawal.
AB  - Serum and potassium withdrawal-induced cell death of cerebellar granule cells is
      one of the most popular models used for studying neuronal apoptosis in vitro, and
      it is generally assumed that compounds preventing cell death in this model
      prevent apoptosis. In the present study we demonstrate that serum and potassium
      withdrawal induces a mixture of apoptosis and necrosis rather than apoptosis
      only. Each of these death mechanisms could be blocked by activation of different
      pathways, such as raising cAMP production or stimulation of the IGF-1 receptor.
      Studies on serum and potassium withdrawal-induced cell death of cerebellar
      granule cells should therefore carefully assess whether a given compound is
      preventing apoptosis or necrosis using appropriate techniques.

PMID- 9141077
TI  - Expression of MHC class II CD4+ and ED1 molecules in association with selective
      hippocampal neuronal degeneration after long-term adrenalectomy.
AB  - The neuroendocrine and the immune systems are interconnected. Monoclonal
      antibodies against major histocompatibility complex (MHC) class I, class II, CD4,
      CD8, pan T cells, and macrophages were used for immunostaining brains from
      adrenalectomized (ADX) and shamoperated rats to investigate the potential
      involvement of the immune/inflammatory mechanisms in the neurodegeneration of
      hippocampus after ADX. Our results demonstrate upregulation of MHC class II, CD4
      antigens and activated microglial marker-ED1 expression selectively in the
      hippocampus after ADX. The absence of CD5 reactivity precludes that these
      activated cells were T lymphocytes. The activated microglial cells may either be
      instrumental in the hippocampal neuronal loss or activated secondarily to the
      neuronal degeneration after long-term adrenalectomy.

PMID- 9141078
TI  - Topography of spatially enhanced human short-latency somatosensory evoked
      potentials.
AB  - In the present study modern high resolution electroencephalography (EEG) was used
      to spatially enhance human median nerve short-latency somatosensory evoked
      potentials (SEPs). It was shown that the spatially enhanced N30 consisted of two
      frontal subcomponents, one located in the frontal-lateral area of the scalp, the
      other located in the frontal-mesial area. Both of these subcomponents were most
      reduced in amplitude (or disappeared) during concomitant hand movement
      ipsilateral to the stimulus, but were differentially influenced by executed
      contralateral movement and imagined ipsilateral movement. These results support
      the hypothesis of an involvement of the frontal-mesial cortex (including the
      supplementary motor area) in the generation of the frontal N30.

PMID- 9141080
TI  - Measurement of nitric oxide in the rat cerebral cortex during hypercapnoea.
AB  - Changes in nitric oxide (NO) concentration and cerebral blood flow (CBF) in the
      parietal cortex during hypercapnoea were investigated in anaesthetized rats,
      using a NO-selective electrode and laser Doppler flowmetry. When hypercapnoea was
      induced by inhalation of 5% CO2 for 10 min, both the NO concentration and CBF
      increased. After administration of 7-nitroindazole, a neuronal NO synthase (nNOS)
      inhibitor, both the basal NO and CBF decreased, and responses to hypercapnoea
      were also significantly suppressed by 70.1% and 73.2%, respectively, compared
      with the control state. These results suggest that NO derived from nNOS is
      involved not only in maintaining resting cerebral circulation but also in
      regulating CBF response during hypercapnoea.

PMID- 9141079
TI  - Increased cerebrospinal fluid concentration of aspartate but decreased
      concentration of nitric oxide breakdown products in women experiencing visceral
      pain during active labour.
AB  - The aim of the present study was to investigate some putative neurotransmitters
      involved in nociception and pain in parturients during active labour experiencing
      intense visceral pain. The concentration of the excitatory amino acid aspartate
      was significantly increased, and there was a tendency for an increase in
      glutamate, in lumbar cerebrospinal fluid (CSF) of parturients in active vaginal
      labour compared with control patients without pain subjected to elective
      caesarean section. The CSF concentration of the nitric oxide breakdown product
      nitrate was significantly decreased in parturients compared with control patients
      and healthy volunteers. No significant differences in the concentrations of
      substance P, substance P-endopeptidase or met-enkephalin were detected between
      parturients and controls. Our data suggest a paradoxical negative relationship
      between CSF concentrations of excitatory amino acids and nitric oxide in labour
      pain. The mechanisms behind this finding is unclear at present.

PMID- 9141081
TI  - c-Jun and cyclin D1 proteins as mediators of neuronal death after a focal
      ischaemic insult.
AB  - c-Jun, a transcriptional activator, as well as cyclin D1, a key regulator of the
      cell cycle, have been described in vitro as mediators of programmed neuronal
      death. After trophic factor deprivation, the activation of c-jun and cyclin D1
      genes is considered as a necessary step within the cellular machinery that leads
      to cell death. We show here that both c-Jun and cyclin D1 proteins are present in
      neurones within the infarcted area after experimental cerebral ischaemia in the
      mouse. Since their presence was associated with DNA fragmentation revealed by the
      TUNEL procedure, we propose that c-Jun and cyclin D1 are involved in the process
      of neuronal death.

PMID- 9141083
TI  - BDNF is required for the normal development of taste neurons in vivo.
AB  - The vallate gustatory epithelium of neonatal trkB null mutant mice (-/-) lacked
      innervation. This prompted the evaluation of null mutant mice corresponding to
      the three neurotrophin ligands for tyrosine kinase receptor B (TrkB): brain
      derived neurotrophic factor (BDNF), neurotrophin (NT)3, NT4. The vallate
      gustatory epithelium of nt3-/- mice and of nt4-/- mice appeared normal. Only bdnf
      /- mice had a vallate papilla that was stunted, sparsely innervated, and lacked
      up to 98% of its taste buds. All three defects persisted. For example, the
      vallate papilla of 12-day-old bdnf-/- mice remained markedly less well innervated
      than the vallate of 7-day-old or newborn bdnf+/+ mice. The foliate taste papillae
      of neonatal bdnf-/- mice had similar defects. We conclude that the normal
      development of taste neurons requires BDNF.

PMID- 9141082
TI  - Distribution of beta-amyloid in the canine brain.
AB  - The distribution of amyloid-beta protein (A beta) in the canine brain was
      demonstrated by immunochemistry on serially sectioned tissues from 10 aged mixed
      breed dogs. Summation of quantitative data and relegation to anatomical sites for
      the 10 dogs showed A beta to be widely distributed in the cortex and hippocampus
      while completely absent in the brain stem and cerebellum. The highest density of
      A beta was in the dentate gyrus of the hippocampus. Cortical areas exhibiting the
      greatest A beta deposition were the posterior and medial suprasylvius gyrus and
      the proreus gyrus of the frontal lobe. Unlike humans the canine entorhinal
      cortex, amygdala, basal ganglia and olfactory bulbs were rarely affected. This
      suggested that the highly developed olfactory pathways of the canine are
      generally spared from A beta deposition.

PMID- 9141084
TI  - Bistable behaviour in a neocortical neurone model.
AB  - Intracellular recordings have shown that neocortical pyramidal neurones have an
      intrinsic capacity for regenerative firing. The cellular mechanism of this firing
      was investigated by computer simulations of a model neurone endowed with standard
      action potential and persistent sodium (gNaP) conductances. The firing mode of
      the neurone was determined as a function of leakage and NaP maximal conductances
      (gl and gNaP). The neurone had two stable states of activity (bistable) over wide
      range of gl and gNaP, one at the resting potential and the other in a
      regenerative firing mode, that could be triggered by a transient input. This
      model points to a cellular mechanism that may contribute to the generation and
      maintenance of long-lasting sustained neuronal discharges in the cerebral cortex.

PMID- 9141085
TI  - Cloning and characterization of the Drosophila presenilin homologue.
AB  - Mutations in two genes, PS1 and PS2, coding for the presenilins, have been linked
      to the early onset form of familial Alzheimer's disease (AD). Here we report the
      identification of a Drosophila melanogaster homologue of human PS genes, Dps,
      which maps to band 77B-C on chromosome 3 and is expressed at multiple
      developmental stages. The predicted amino acid sequence of the Dps product is 53%
      identical to human presenilins, with the greatest similarity in the putative
      transmembrane domains, the hydrophobic domains at the beginning and the end of
      the cytoplasmic TM6-TM7 loop and the C-terminus. Analysis of Dps in a genetically
      tractable model system such as Drosophila may provide insight into the mechanisms
      of Alzheimer's disease (AD) necessary for the development of rational therapeutic
      approaches.

PMID- 9141086
TI  - Control conditions in the fear-potentiated startle response paradigm.
AB  - In the present study, the fear-potentiated startle response paradigm was modified
      in order to investigate the decrease in control startle levels often observed
      after administration of anxiolytic drugs. The within-animal comparison of control
      startle amplitudes and fear-potentiated startle amplitudes normally used was
      replaced by a between-animal comparison. Moreover, the experimental design was
      extended with an additional control group, a no-shock group. The anxiolytics
      diazepam and chlordiazepoxide were used as pharmacological tools. The main
      findings were that both benzodiazepines dose-dependently reduced control startle
      amplitudes and no-shock startle amplitudes equally, suggesting that shock
      associated contextual cues are not responsible for the drug-induced decrease in
      control startle amplitudes in the fear-potentiated startle response paradigm.

PMID- 9141087
TI  - Upregulation of leptin receptor mRNA expression in obese mouse brain.
AB  - Leptin receptor gene expression in the brains of lean (+/+) and obese (ob/ob)
      C57Bl/6 mice was examined using a non-radioactive in situ hybridization detection
      method. Significant increases in leptin receptor mRNA expression were found in
      the ventromedial and arcuate hypothalamic nuclei, piriform and olfactory cortices
      and medial habenular nucleus. There were very minor changes in the amount of
      leptin receptor mRNA expression in hippocampus proper (CA1-3). Results indicated
      that leptin receptor is upregulated when there is a lack of functional leptin, as
      in hereditary obese (ob/ob) mice. It is also suggested that leptin receptor may
      be an autoreceptor.

PMID- 9141088
TI  - Short duration synchronization of human theta rhythm during recognition memory.
AB  - Structures within the medial temporal lobe, particularly the hippocampus, have
      long been implicated in human episodic memory. The same structures are known to
      generate EEG in the theta frequency range in animals. The aim of this experiment
      was to investigate the time course of changes in the human theta rhythm during a
      word recognition memory task. In the period 125-250 ms after the visual
      presentation of a word, theta power increased by an average of 13% compared with
      the prestimulus baseline period and this increase was more than twice as great
      for repeated words (18%) as for new ones (8%). These results show that there are
      short duration changes in the human theta rhythm associated with recognition
      memory.

PMID- 9141089
TI  - Heme oxygenase-2 and nitric oxide synthase in guinea-pig intracardiac neurones.
AB  - There is increasing evidence that carbon monoxide (CO), like nitric oxide (NO),
      may be a neuronal messenger molecule. This study investigated the expression of
      heme oxygenase-2 (HO-2), the enzyme responsible for the synthesis of CO, by
      intracardiac neurones. Many, if not all newborn guinea-pig intracardiac neurones
      in culture were HO-2-immunoreactive. Furthermore, double labelling showed that a
      relatively small subpopulation of these neurones also expressed NO
      synthase/nicotinamide dinucleotide phosphate (NADPH)-diaphorase (NOS/NADPH-d)
      activity. These findings suggest that intracardiac neurones can synthesize CO and
      that CO may be fundamental to their function. Comparison of the proportions of
      intracardiac neurones that contain HO-2 with those that express NOS/NADPH-d
      activity also indicates that CO may be more important than NO in the intrinsic
      neuronal control of the heart.

PMID- 9141090
TI  - Difference in cochlear efferent activity between musicians and non-musicians.
AB  - The present study aimed to confirm and extend the finding, suggested by the
      results of a previous study, of different auditory neural efferent functioning in
      musicians compared with non-musicians. The activity of the medial olivocochlear
      bundle (MOCB), an auditory efferent subsystem, was measured through the
      contralaterally induced attenuation of the amplitude of evoked otoacoustic
      emissions (EOAEs) in two groups, one of musicians and one of non-musicians,
      paired for age and sex. The results indicated a statistically significant
      difference between the two groups, with the musicians showing greater amplitude
      reduction upon contralateral noise stimulation than non-musicians (U-test, U =
      204, p < 0.025, n = 32). These results indicate greater MOCB activity in
      musicians than in non-musicians. The possible origins and implications of this
      finding are discussed.

PMID- 9141091
TI  - SNAP25 and GAP-43 behave differently in decentralized rat superior cervical
      ganglia.
AB  - The behaviour of synaptosome associated protein of mol. wt 25 kDa (SNAP25) in
      decentralized rat superior cervical ganglia (SCG) was investigated in order to
      observe its possible involvement in adrenergic postganglionic neuronal
      plasticity. Immunofluorescence and immunoblot results showed that the protein was
      increased in the nerve terminals in irides 8 days after operation. The intra
      ganglionic nerve terminals and nerve fibres differed in their content of GAP-43
      and SNAP25: GAP-43, which could not be observed at 1 day, appeared at 3 days
      after cutting the cervical sympathetic trunk, whilst SNAP25-immunoreactive
      material was still undetectable at this time. Immunoblot data also showed that
      SNAP25 did not reach control levels at 3 and 8 days after decentralization, in
      contrast to GAP-43. This observation may imply that SNAP25 is rapidly transported
      to its functional destinations immediately after synthesis and is possibly mainly
      involved in the remodelling of long projection pathways.

PMID- 9141092
TI  - Cingulate function in depression: a potential predictor of treatment response.
AB  - The relationship between pretreatment regional cerebral glucose metabolism and
      eventual antidepressant drug response was measured using positron emission
      tomography (PET) in hospitalized patients with unipolar depression. Rostral
      anterior cingulate metabolism uniquely differentiated eventual treatment
      responders from non-responders. Hypometabolism characterized non-responders when
      compared with controls, in contrast to responders who were hypermetabolic.
      Metabolism in no other region discriminated the two groups, nor did associated
      demographic, clinical or behavioral measures, including motor speed, cognitive
      performance, depression severity or illness chronicity. Cingulate hypermetabolism
      may represent an important adaptive response to depression and failure of this
      response may underlie poor outcome. A critical role for rostral cingulate area
      24a/b in the limbic-cortical network involved in abnormal mood states is
      proposed.

PMID- 9141093
TI  - Model of a thalamocortical neurone with dendritic voltage-gated ion channels.
AB  - To investigate the functional role of dendrites of thalamocortical neurones, we
      have used our one-compartmental model to construct a multi-compartmental model
      with dendritic regions chosen according to a representative soma-to-dendritic
      terminal path of an X cell of the cat dorsal lateral geniculate nucleus. The
      multi-compartmental model with dendritic low-threshold CA2+ and delayed rectifier
      K+ channels yields more accurate results than the one-compartmental model when
      simulating tonic firing and oscillatory activities, and provides a useful means
      for the study of propagation of excitation on the dendrites.

PMID- 9141094
TI  - Neurotoxicity of apolipoprotein E thrombin cleavage fragments: implications for
      Alzheimer's disease.

PMID- 9141095
TI  - Building bright oral health futures.

PMID- 9141096
TI  - Proceedings from the Pediatric Dentistry Advanced Education Program Directors'
      Symposium.

PMID- 9141097
TI  - Medicare graduate medical education law, regulations, and legislative proposals.

PMID- 9141098
TI  - The impact of managed care on dental clinic administration.

PMID- 9141099
TI  - Financing of pediatric dental postgraduate programs.

PMID- 9141100
TI  - Funding sources for research for advanced education students in pediatric
      dentistry.
AB  - 1. Of the hospital programs, 10 of 17 (41%) reported no funding requirement while
      only 5 of 33 (15%) school based programs reported no funding requirement. 2.
      Departmental funds were identified most often (N = 28) and ranked number one most
      often (N = 16) as the funding source for graduate student research. 3. The
      average level of research funding available for each student ranged from $100 to
      $3,500, with an average of $1,250. 4. One-half of the programs reported no change
      in their funding levels over the past five years. 5. Programs associated with
      dental schools reported more funding opportunities available to their students
      than programs associated with hospitals.

PMID- 9141101
TI  - The manpower issue in pediatric dental education: our job is not finished!

PMID- 9141102
TI  - Producing the next generation of professional educators in pediatric dentistry.
AB  - We will see an abundance of eager, well-prepared aspiring academic pediatric
      dentists only when the market forces make this decision more rational for the
      best and the brightest. Until then, our challenge is to show interested students
      the excitement and vitality of this career path through our own examples. Then,
      once those few are intrigued, it is incumbent upon the system to be prepared to
      foster their interest and help them improve their skills so they are prepared to
      be successful in the academic environment. In addition, supplementation of
      teaching efforts may come from other creative avenues. Potential additional
      sources are found in experienced clinicians as well as modern, media-based
      instructional packages.

PMID- 9141103
TI  - Status of guidelines and the scope of the specialty. The American Academy of
      Pediatric Dentistry Subcommittee on Advanced Education Guidelines. Standards for
      advanced education programs in pediatric dentistry.

PMID- 9141104
TI  - The accreditation process for advanced education programs in pediatric dentistry:
      a look from the inside out.

PMID- 9141105
TI  - A national in-service training examination for advanced education students in
      pediatric dentistry (PEDSITE).

PMID- 9141106
TI  - Administrative skills for dealing with issues facing contemporary pediatric
      dentistry programs.

PMID- 9141107
TI  - The Internet: implications for the American Academy of Pediatric Dentistry.

PMID- 9141108
TI  - Defining and implementing interprogram research and clinical programs.

PMID- 9141109
TI  - Retrospective review of the effects of rhDNase in children with cystic fibrosis.
AB  - Trials of rhDNase in mixed groups of adults and children with cystic fibrosis
      (CF) have demonstrated improvements in lung function and well-being. This has led
      to many pediatric CF patients receiving regular rhDNase therapy although their
      response to treatment may not be the same as that seen in adults. We have
      retrospectively reviewed the effects of rhDNase during the first year of therapy
      in 65 children receiving the drug at two tertiary referral centers. Outcome
      measures included changes in lung function, oxygen saturation, use of intravenous
      antibiotics, and subjective improvement. Median baseline lung function (% of
      predicted) was 45% for forced expiratory volume in 1 second (FEV1) and 58% for
      forced vital capacity (FVC). At 3-4 months following initiation of therapy the
      group demonstrated median (95% CI) increases of 14.2% (95% CI 7.3; 21.1%) in FEV1
      and 7% (0; 14%) in FVC. Within this wide scatter of responses, one-quarter of
      children deteriorated, but almost 50% showed significant improvements of > 10%. A
      similar pattern was seen at 9 months, with median increases for the group of
      11.1% (0; 18.8%) in FEV1 and 5.6% (0; 17%) in FVC, again with approximately one
      third of the group deteriorating and one-half improving significantly.
      Intravenous antibiotic use decreased significantly. Almost all the children
      (89%), including those with a fall in lung function, described subjective
      improvement. There were no predictive markers at baseline of a good response to
      the drug. However, there was a good correlation between lung function response at
      3 months and that at 6, 9, and 12 months. Thus, children respond to rhDNase at
      least as well as adults, and a therapeutic trial is justified in those over 5
      years with significantly impaired lung function. Response is highly variable,
      making careful individual assessment mandatory. Baseline characteristics are not
      useful in predicting those children who will respond well to treatment, but long
      term response to the drug can be predicted on the basis of spirometric
      improvement at 3 months. Therefore, this would be a useful time period for a
      therapeutic trial.

PMID- 9141111
TI  - Yield from flexible bronchoscopy in children.
AB  - Flexible fiberoptic (FO) bronchoscopy can now be undertaken readily in children
      using topical anesthesia and light sedation and has largely supplanted rigid open
      tube (OT) bronchoscopy for diagnostic purposes. The present study examined the
      contribution of the FO bronchoscope to clinical management in children presenting
      with specific types of problems. We examined the first 200 consecutive flexible
      bronchoscopies performed in 1995 in children under 18 years of age (median age,
      2.27 years). Indications for bronchoscopy were noisy breathing (26.5%), recurrent
      pneumonia (21.0%), suspected pneumonia in an immunocompromised patient (10.5%),
      atelectasis or bronchial toilet (12.5%), possible foreign body aspiration
      (13.0%), and miscellaneous other reasons (16.5%). Inspection of the airway was
      abnormal in 67.0% of all investigations and made a clinically meaningful
      contribution to management in 67.5%, especially in those with noisy breathing
      (98.1%), possible foreign body aspiration (100%), and atelectasis (76.0%).
      Bronchoalveolar lavage (BAL) cytology was abnormal in 80.4% of the 107 lavages,
      but contributed little to management except in those with recurrent pneumonia
      (73.8%). Bacteria were isolated in 26.6% of the 109 specimens cultured, but this
      finding rarely affected management. Fungi were isolated in 47.4% of the 19
      lavages in the immunocomprised group. Together, inspection, BAL and microbiology
      contributed to management in a mean of 90.5% (range, 76.2-100%) of patients in
      the various groups. We concluded that a high yield of clinically meaningful
      information can be expected from FO bronchoscopy in children when coupled with
      BAL and microbiological studies of lavage fluid.

PMID- 9141110
TI  - Effect of nebulizer type and antibiotic concentration on device performance.
AB  - We compared the performance of selected ultrasonic and jet nebulizers when
      aerosolizing several antibiotic formulations to determine optimum combinations
      for delivery of a respirable antibiotic aerosol. Three ultrasonic devices were
      tested: the UltraNeb 99/100, the UltraAIR and the Aerosonic. The reusable jet
      nebulizers were the Dura ProNeb, Pari-LL and the Sidestream. The six disposable
      jet nebulizers were Marquest Acorn II, Hudson T Updraft II, Baxter MistyNeb, Pari
      LC, Pari IS-2, and a disposable Sidestream. Each jet was tested with four
      compressors: a DeVilbiss AP-50, a Pulmo-Aide, a DuraNeb and a PariMaster. All
      nebulizing systems were initially tested with normal saline. From the initial
      data, six jet nebulizers and one ultrasonic device were tested with varying
      concentrations of tobramycin, gentamicin, ceftazidime, ciprofloxacin and
      colistin. Output was assessed by measuring volume (milliliters per minute), and
      amount of drug (milligrams per minute) nebulized. We then measured mean particle
      size of the antibiotic aerosol with seven jet nebulizers and two different
      compressors, Pulmo-Aide and PariMaster, and two ultrasonic devices. The rate of
      nebulization of saline and antibiotic solutions (milliliters per minute) was
      greater with the ultrasonic device(s) than all jet nebulizer systems tested.
      Increasing the reservoir antibiotic concentration increased the drug output
      (milligrams per minute) with the jet nebulizers to a maximum, followed by
      decreasing output. When antibiotic concentrations were increased the output
      decreased more precipitously with the ultrasonic devices than with the jet
      nebulizers. At the highest antibiotic concentrations tested, the ultrasonic
      devices had the lowest output. Particle size distribution was most dependent on
      the specific jet device, with particle size distribution less affected by a
      specific antibiotic or its concentration. Higher reservoir concentrations can be
      utilized for increasing output of respirable antibiotic aerosols by jet
      nebulizers. We conclude that antibiotic output is dependent upon both the
      nebulizing system and the reservoir concentration of antibiotic.

PMID- 9141112
TI  - Dose titration of nebulized budesonide in young children.
AB  - We compared the clinical effect of the glucocorticoid budesonide delivered from
      two nebulizers Aiolos and Pari LL in 38 children less than 4 years of age (mean
      age, 20.2 months) with chronic wheeze. The design was a controlled, single-blind,
      randomized, cross-over, dose titration study. After a 1-week run-in, patients
      were randomized to treatment with 1 mg budesonide b.i.d. for 2 weeks from either
      an Aiolos or a Pari LL nebulizer. This was followed by a gradual dose reduction
      period during which the budesonide dose was reduced at 2-week intervals until
      unacceptable asthma symptoms appeared or the placebo level was reached. The
      patient was then switched to budesonide 1 mg b.i.d. from the other nebulizer for
      2 weeks, after which the dose was reduced at 2-week intervals as described for
      the first period. Patients who completed the study on placebo for 2 weeks without
      deterioration of their asthma were not included in the statistical analysis.
      During Period #1 the minimum effective dose of budesonide was 2 mg/day in 9
      patients, 1 mg/day in 10 patients, and 0.5 mg/day in 13 patients. In Period #2
      the corresponding figures were 14, 5, and 13 patients. Six patients were excluded
      after the first period because their asthma control did not deteriorate during
      dose reduction and when finishing on placebo for 2 weeks. For both nebulizers the
      reduction in budesonide dose was associated with a small increase in symptoms and
      use of rescue terbutaline. The mean dose of budesonide delivered to the patient
      by the Aiolos was twice as large as that delivered by the Pari LL: 26% vs. 13% of
      the nominal dose assessed by the filter method. Nevertheless, no statistically
      significant difference in clinical effect or mean minimal effective dose (1.1 mg
      for Aiolos and 1.2 mg for Pari LL) could be detected between the two nebulizers.
      No serious adverse events were observed. We conclude that the minimal effective
      dose of nebulized budesonide varies from 0.5 to 2.0 mg/day in young children with
      asthma. A higher drug delivery, as assessed by the filter method, does not
      necessarily result in better clinical control or lower minimal effective dose.
      Further studies are needed to assess whether this is due to insufficient
      sensitivity of the study design in detecting a difference in clinical effect, or
      whether measurements of drug delivery by the filter method do not reflect lung
      deposition or clinical effect in young children with wheezing.

PMID- 9141113
TI  - Repeatability of methacholine challenges in 2- to 4-year-old children with
      asthma, using a new technique for quantitative delivery of aerosol.
AB  - To determine the repeatability of bronchial responsiveness in awake young
      children, two methacholine challenge tests were performed on separate days in 16
      children with stable asthma (mean age, 3 3/4 years). Methacholine was
      administered using a new method for quantitative delivery of aerosol that
      eliminates the effect of dilution of the aerosol by entrainment of air and
      enables quantitative delivery of aerosol according to body weight. Respiratory
      function was monitored by measurement of respiratory resistance by the
      interrupter technique (Rint), respiratory resistance and reactance at 5 Hz (Rrs5,
      Xrs5) by the impulse oscillation technique, transcutaneous measurements of oxygen
      (PtcO2), and specific airway resistance (sRaw). Repeatability was evaluated by
      determining the provocative dose that caused a defined percentage of change
      relative to baseline (PD%: Rint PD30, Rrs5 PD30, Xrs5 PD80, PtcO2 PD10, and sRaw
      PD80. Repeatability was estimated from the difference between the PD% obtained at
      the time of the two tests. Using the numeric value of these differences, the
      repeatability of Xrs5 PD60, PtcO2 PD10, and sRaw PD50 was [mean (SD)]: [0.8
      (0.5)] [0.5 (0.4)] and [0.7 (0.6)] doubling doses, respectively. Rint PD30 and
      Rrs5 PD30 proved to be less reproducible: [1.2 (1)] and [1.6 (0.9)] doubling
      doses, respectively. The new method of aerosol delivery offers a means of
      standardizing the bronchoconstrictor stimulus, and the results show that
      estimates of bronchial responsiveness in young children can be obtained
      reproducibly within one doubling dose of methacholine.

PMID- 9141114
TI  - Prediction of surfactant dysfunction in term infants by the click test.
AB  - Pulmonary surfactant dysfunction (inactivation, deficiency) has been implicated
      in term neonates with respiratory failure. This study has evaluated the click
      test, a biophysical test for surfactant function, which will be useful in rapidly
      and reliably identifying term neonates with surfactant dysfunction. Samples of
      tracheal and or gastric aspirates (0.2 ml) from 55 neonates, varying from 36 to
      42 weeks of gestational age, with respiratory distress and fractional inspired
      oxygen concentration requirements of > 0.5 were shaken with 95% ethanol. Once
      bubbles formed the samples were examined in air-free water under a microscope. In
      a positive click test, the bubbles rhythmically increase and then decrease in
      size, denoting the presence of active surfactant. When few bubbles were observed,
      the specimen was labelled as equivocal, and if none were seen, it was called
      negative. Surfactant dysfunction (negative or equivocal test) was consistently
      seen in respiratory distress syndrome (RDS), transient tachypnea of the newborn,
      and severe meconium aspiration syndrome (MAS). Preliminary data suggest that the
      click test will provide a rapid and early diagnosis of surfactant dysfunction in
      term neonates. This should facilitate early treatment with exogenous surfactant
      in RDS, by early diagnosis of surfactant deficiency, and provide justification
      for immediate and ongoing surfactant treatment in newborns with MAS. The click
      test can provide a diagnostic tool for surfactant dysfunction and deficiency in
      randomized controlled trials of therapy in those disease states in which
      exogenous surfactant therapy may be useful.

PMID- 9141115
TI  - Markers and mediators of inflammation in neonatal lung disease.

PMID- 9141116
TI  - Inflammatory pseudotumor of the trachea in a ten-month-old infant.
AB  - Inflammatory pseudotumors occur through a non-neoplastic process that involves
      abnormal proliferation of spindle cells (myoblasts and fibroblasts) with an
      inflammatory cell infiltrate. Clinically, radiographically, and grossly these
      lesions mimic malignant neoplasms but are readily distinguished histologically.
      We report an infant who presented with an inflammatory pseudotumor of his trachea
      that caused severe stridor.

PMID- 9141117
TI  - Benign cystic teratoma simulating organized empyema.

PMID- 9141118
TI  - Short-course, high-dose corticosteroid treatment in six children with late ARDS.

PMID- 9141119
TI  - rhDNase in acute asthma.

PMID- 9141120
TI  - Aspergillus organisms in patients with cystic fibrosis.

PMID- 9141121
TI  - The effects of prosthesis mass on metabolic cost of ambulation in non-vascular
      trans-tibial amputees.
AB  - The effect of prosthesis mass on the metabolic cost of steady-state walking was
      studied in ten male non-vascular trans-tibial amputees (TTAs) and ten non-amputee
      controls. The subjects underwent four trials of treadmill ambulation, with each
      trial performed for nine minutes at level grade and 76 m/min. Twenty minutes of
      seated rest followed each trial. During trials numbers one and two, TTAs
      ambulated without mass added to their prosthesis. During the third and fourth
      trials, either 454 or 907 grammes mass (1 or 2lbs mass respectively) were
      randomly assigned and added to either the prosthesis or the leg of the non
      amputee control. Subjects were blinded to the amount of mass added to their limb.
      Within-group comparisons across the four trials showed significant differences in
      oxygen consumption (VO2) and heart rate (HR) between the two non "mass added"
      trials, but no effect for addition of mass. The VO2 of TTAs was only 0.6
      ml/kg/min (4.7 percent) greater during walking following the addition of 907
      grammes to the prosthesis than without mass addition at all, while HR averaged
      only 1.4 beats/min. higher under the same testing condition. Pearson-product
      moment correlations echoed these findings, as moderate, but in all cases,
      negative correlations were observed for associations among the factors of subject
      age, stump length, and prosthesis-shoe weight, and both VO2 and HR. It was
      concluded that adding up to 907 grammes mass to a non-vascular TTA's prosthesis
      will not significantly increase the energy expenditure or HR at a normal walking
      speed, and that elevated energy cost of ambulation in repeated measures testing
      without mass added may reflect task familiarization and not an added burden of
      prosthesis mass.

PMID- 9141122
TI  - Energy storage and release of prosthetic feet. Part 1: Biomechanical analysis
      related to user benefits.
AB  - The energy storing and releasing behaviour of 2 energy storing feet (ESF) and 2
      conventional prosthetic feet (CF) were compared (ESF: Otto Bock Dynamic Pro and
      Hanger Quantum; CF: Otto Bock Multi Axial and Otto Bock Lager). Ten trans-tibial
      amputees were selected. The study was designed as a double-blind, randomised
      trial. For gait analysis a VICON motion analysis system was used with 2 AMTI
      force platforms. A special measuring device was used for measuring energy storage
      and release of the foot during a simulated step. The impulses of the
      anteroposterior component of the ground force showed small, statistically non
      significant differences (deceleration phase: 22.7-23.4 Ns; acceleration phase:
      17.0-18.4 Ns). The power storage and release phases as well as the net results
      also showed small differences (maximum difference in net result is 0.03 J kg-1).
      It was estimated that these differences lead to a maximum saving of 3% of
      metabolic energy during walking. It was considered unlikely that the subjects
      would notice this difference. It was concluded that during walking differences in
      mechanical energy expenditure of this magnitude are probably not of clinical
      relevance. Ankle power, as an indicator for energy storage and release gave
      different results to the energy storage and release as measured with the special
      test device, especially during landing response. In the biomechanical model
      (based on inverse dynamics) used in the gait analysis the deformation of the
      material is not taken into consideration and hence this method of gait analysis
      is probably not suitable for calculation of shock absorption.

PMID- 9141123
TI  - Energy storage and release of prosthetic feet. Part 2: Subjective ratings of 2
      energy storing and 2 conventional feet, user choice of foot and deciding factor.
AB  - This paper is the second part of a study on biomechanical and functional
      properties of prosthetic feet. The first part dealt with a biomechanical analysis
      related to user benefits. This part deals with subjective ratings and deciding
      factors for trans-tibial amputees using 2 energy storing feet (ESF) and 2
      conventional feet (CF). The Otto Bock Dynamic Pro and Hanger Quantum feet were
      used as ESF and the Otto Bock Multi Axial and Otto Bock Lager feet were used as
      CF. Ten trans-tibial amputees, active walkers, without stump problems, were
      selected (mean age: 49 years old). The study was designed as a double-blind,
      randomised trial and for each foot there was a habituation period of 2 weeks. Two
      questionnaires were designed. (A) concerned information about the preference of
      the subjects and (B) concerned the order of importance of difference aspects
      concerning a prosthesis. Results indicated that no clear preference for either
      the ESF or the CF existed and that the individual preference is not related to
      age. The items 'ability to walk fast' and 'no fatigue during walking', score
      statistically significantly worse for the CF2. With the small contrast between
      the ESF and CF, in relation to energy storing capacities, the subjects cannot
      distinguish between the ESF and CF. The 'absence of stump pain' and 'stability
      while walking' are ranked as most important aspects concerning a prosthesis. The
      perception of stability is likely to be related to the level and kind of
      activities the subject performs.

PMID- 9141124
TI  - The life style of young persons after lower limb amputation caused by injury.
AB  - In order to determine whether lower limb amputation changes the social life and
      free time activities of persons who were at the time of amputation young, a
      questionnaire was sent to 519 persons after trans-tibial or higher level of lower
      limb amputation who were at the time of amputation younger than 51 years,
      amputated because of injury, permanently resident in Slovenia and had visited the
      outpatient prosthetics clinic of the Rehabilitation Institute of Slovenia at
      least once in the last five years (1989-94). There 228 responses, which were
      statistically analysed. It was found that after amputation most persons
      participated less frequently in social activities, especially persons who were
      older at the time of amputation and also those who are older today. Changes in
      participation in social activities were not influenced by level of education.
      Free time activities changed after amputation. Some 93 persons completely changed
      their free time activities and only 30 were still interested in the same
      activities as before. The three most frequent free time activities before
      amputation were cycling, team ball games and farm work. After amputation they
      were reading, watching television and/or listening to radio and music and
      housekeeping. It is concluded that lower limb amputation severely changes the
      social life and free time activities of persons who were young at the time of
      amputation.

PMID- 9141125
TI  - Lifelikeness in multilayered digital prostheses.
AB  - The appearance of the skin is dependent on the optical properties of the various
      layers of tissue and the presence of pigments. In order to reproduce the
      lifelikeness of the skin in developing digital prostheses, a multiple layered
      moulding technique was utilised. The prosthesis was moulded in two coloured
      layers, an outer layer and an inner layer. Four combinations of multiple coloured
      layers and two single coloured layers varying in their optical properties and
      base colours were assessed. In two groups an additional intermediate layer of
      detailed colours was added between the two layers, to enhance the creaselines,
      nails, blood vessels, and other features. All prosthesis were moulded to a total
      thickness of 0.6 mm. This method of moulding was based on the anatomical
      characteristics of the epidermal and dermal layers of the skin and their optical
      characteristics. The aim was to determine which combination of multiple layers
      gave the best outcome and made the prosthesis look lifelike in appearance. The
      appearance and lifelikeness of the prostheses were qualitatively assessed by a
      panel of assessers divided according to their vocation. The study showed that the
      best combination for moulding the prosthesis in multiple layers was to have the
      outer layer translucent and the inner layer opaque. An intermediate layer should
      be incorporated to enhance the more prominent surface features and the nails. The
      base colour of the inner layer should be darker than the outer layer to allow the
      intermediate layer to have a reflective background.

PMID- 9141126
TI  - The influence of the reciprocal cable linkage in the advanced reciprocating gait
      orthosis on paraplegic gait performance.
AB  - A wide variety of mechanical orthoses is available to provide ambulation to
      paraplegic patients. Evaluation of energy cost during walking in each of these
      devices has been acknowledged as an important topic in this field of research. In
      order to investigate the benefits of a ballistic swing on gait performance in the
      Advanced Reciprocating Gait Orthosis (ARGO) a study was conducted in which the
      ARGO was compared with an orthosis with freely swinging legs. This Non
      Reciprocally linked Orthosis (NRO) was obtained by removing the reciprocal
      linkage in the subjects' own ARGOs. Subsequently, flexion/extension limits were
      mounted to permit adjustment of stride length. Six male paraplegic subjects with
      lesions ranging from T4 to T12 were included in the study. A single case
      experimental design (B-A-B-A) was conducted in order to improve internal
      validity. Biomechanical and physiological parameters were assessed and the
      subjects' preference for either ARGO or NRO was determined. It was found that
      large inter-individual differences produced insufficient evidence in this study
      to draw general conclusions about difference in energy expenditure between both
      orthoses. However, individual analysis of the results showed a reduction of
      oxygen cost (range: 4%-14%) in the NRO in T9 and T12 lesions, while oxygen cost
      in subjects with T4 lesions increased markedly (22% and 40%). It is concluded
      that patients with low level lesions could benefit in terms of oxygen lost from
      removing the reciprocal cable linkage in the ARGO. However, only one subject
      preferred the NRO for walking, whereas none of the subject chose the NRO for use
      in daily living activities. Removal of the reciprocal cable linkage in the ARGO
      may not be desirable for these patients.

PMID- 9141127
TI  - Powered wheelchairs: are we enabling or disabling?
AB  - Following the unsuccessful issue of three powered indoor National Health Service
      (NHS) wheelchairs, a survey was carried out of 40 users in a London wheelchair
      service to identify the problems with issue and possible areas for improvement to
      practice. The survey identified improvements that were necessary both from the
      service and the manufacturers' booklets. The improvements include the issue of
      written instructions and information to complement verbal instruction given at
      handover. Such information should be as interesting to read as possible, make use
      of appropriate language and diagrams (especially in area where English is often
      not the first language), colour, text and print size to maximise comprehension to
      these severely disabled users and often their elderly relatives or carers. The
      importance of the role of the rehabilitation engineer in training the user,
      giving instruction at handover and annual review are highlighted to ensure that
      the equipment remains working, suitable and up to date for the individual's
      needs. Training in interpersonal and communication skills and the importance of
      recall should also be emphasised. The implementation of the findings should lead
      to increasing contact with the service by the user, reduction in repair and
      replacement costs, regular review, correct supply and will therefore enable users
      to increase their independence with appropriate equipment.

PMID- 9141128
TI  - Hydration of an alpha-helical peptide: comparison of theory and molecular
      dynamics simulation.
AB  - We present a statistical mechanical description of biomolecular hydration that
      accurately describes the hydrophobic and hydrophilic hydration of a model alpha
      helical peptide. The local density of water molecules around a biomolecule is
      obtained by means of a potential-of-mean-force (PMF) expansion in terms of pair-
      and triplet-correlation functions of bulk water and dilute solutions of nonpolar
      atoms. The accuracy of the method is verified by comparing PMF results with the
      local density and site-site correlation functions obtained by molecular dynamics
      simulations of a model alpha-helix in solution. The PMF approach quantitatively
      reproduces all features of the peptide hydration determined from the molecular
      dynamics simulation. Regions of hydrophobic hydration near the C alpha and C beta
      atoms along the helix are well reproduced. The hydration of exposed polar groups
      at the N- and C-termini of the helix are also well described by the theory. A
      detailed comparison of the local hydration by means of site-site radial
      distribution functions evaluated with the PMF theory shows agreement with the
      molecular dynamics simulations. The formulation of this theory is general and can
      be applied to any biomolecular system. The accuracy, speed of computation, and
      local character of this theory make it especially suitable for studying large
      biomolecular systems.

PMID- 9141129
TI  - Structure and dynamics of the M13 coat signal sequence in membranes by
      multidimensional high-resolution and solid-state NMR spectroscopy.
AB  - The polypeptide corresponding to the signal sequence of the M13 coat protein and
      the five N-terminal residues of the mature protein was prepared by solid-phase
      peptide synthesis with a 15N isotopic label at the alanine-12 position.
      Multidimensional solution NMR spectroscopy and molecular modeling calculations
      indicate that this polypeptide assumes helical conformations between residues 5
      and 20, in the presence of sodium dodecylsulfate micelles. This is in good
      agreement with circular dichroism spectroscopic measurement, which shows an alpha
      helix content of approximately 42%. The alpha-helix comprises an uninterrupted
      hydrophobic stretch of < or = 12 amino acids, which is generally believed to be
      too short for a stable transmembrane alignment in a biological bilayer. The
      monoexponential proton-deuterium exchange kinetics of this hydrophobic helical
      region is characterized by half-lives of 15-75 minutes (pH 4.2, 323 K). When the
      polypeptide is reconstituted into phospholipid bilayers, the broad anisotropy of
      the proton-decoupled 15N solid-state NMR spectroscopy indicates that the
      hydrophobic helix is immobilized close to the lipid bilayer surface at the time
      scale of 15N solid-state NMR spectroscopy (10(-4) seconds). By contrast, short
      correlation times, immediate hydrogen-deuterium exchange as well as nuclear
      Overhauser effect crosspeak analysis suggest that the N and C termini of this
      polypeptide exhibit a mobile random coil structure. The implications of these
      structural findings for possible mechanisms of membrane insertion and
      translocation as well as for membrane protein structure prediction algorithms are
      discussed.

PMID- 9141130
TI  - High resolution fast quantitative docking using Fourier domain correlation
      techniques.
AB  - A 'docking' method based on finite grid forcefield sampling is proposed for fast
      evaluation of interaction energies between macromolecules and ligands. Forcefield
      used to calculate interaction energies utilizes a potential energy function
      composed of a 1/r-dependent electrostatic term and a (6-12) Lennard-Jones term
      for van der Waals interactions. Fast evaluation makes use of the convolution
      theorem allowing a point-by-point N-dimensional correlation in direct space to be
      replaced by a simple multiplication in spatial frequency space. Predictive
      accuracy was assessed by using seven protein-ligand complexes available from the
      Brookhaven Data Bank and determined crystallographically to high resolution.
      Successful prediction of ligand position and determination of ligand-protein
      interaction enthalpy was dependent on forecefield sampling grid size. Minimum
      interaction enthalpy calculated for four protein-ligand complexes coincided with
      crystallographic structures that used sampling grid sizes of 0.25 A resolution
      and was independent of ligand starting position and orientation. Successful
      docking was obtained for the remaining complexes at same grid resolution provided
      ligand starting positions were not randomized. Sensitivity of the docking
      algorithm to starting orientation was a consequence of tight fit of respective
      ligand structures with their protein target sites for these three cases and can
      be circumvented by using finer rotational sampling grids for the ligand.
      Boltzmann statistics derived from calculated interaction energies successfully
      extracted the observed ribonuclease A cytidylic acid complex from a manifold of
      similar interaction energies. The proposed method was able to reproduce the
      observed crystallographic complex by using a dynamical description of ligand.

PMID- 9141131
TI  - A model of insulin fibrils derived from the x-ray crystal structure of a
      monomeric insulin (despentapeptide insulin).
AB  - The crystal structure of despentapeptide insulin, a monomeric insulin, has been
      refined at 1.3 A spacing and subsequently used to predict and model the
      organization in the insulin fibril. The model makes use of the contacts in the
      densely packed despentapeptide insulin crystal, and takes into account other
      experimental evidence, including binding studies with Congo red. The dimensions
      of this model fibril correspond well with those measured experimentally, and the
      monomer-monomer contacts within the fibril are in accordance with the known
      physical chemistry of insulin fibrils. Using this model, it may be possible to
      predict mutations in insulin that might alleviate problems associated with fibril
      formation during insulin therapy.

PMID- 9141132
TI  - Structure prediction and fold recognition for the ferrochelatase family of
      proteins.
AB  - An alpha/beta barrel is predicted for the three-dimensional (3D) structure of
      Bacillus subtilis ferrochelatase. To arrive at this structure, the THREADER
      program was used to find possible homologous 3D structures and to predict the
      secondary structure for the ferrochelatase sequence. The secondary structure was
      fit by hand to the selected homologous 3D structure then the MODELLER program was
      used to predict the fold of ferrochelatase. Molecular biological information
      about the conserved residues of ferrochelatase was used as the criteria to help
      select the homologous 3D structure used to predict the fold of ferrochelatase.
      Based on the predicted structure possible, ligands binding to the iron and
      protoporphyrin IX are discussed. The structure has been deposited in the
      Brookhaven database as ID 1FJI.

PMID- 9141133
TI  - Simulation of protein conformational freedom as a function of pH: constant-pH
      molecular dynamics using implicit titration.
AB  - Solution pH is a determinant parameter on protein function and stability, and its
      inclusion in molecular dynamics simulations is attractive for studies at the
      molecular level. Current molecular dynamics simulations can consider pH only in a
      very limited way, through a somewhat arbitrary choice of a set of fixed charges
      on the titrable sites. Conversely, continuum electrostatic methods that
      explicitly treat pH effects assume a single protein conformation whose choice is
      not clearly defined. In this paper we describe a general method that combines
      both titration and conformational freedom. The method is based on a potential of
      mean force for implicit titration and combines both usual molecular dynamics and
      pH-dependent calculations based on continuum methods. A simple implementation of
      the method, using a mean field approximation, is presented and applied to the
      bovine pancreatic trypsin inhibitor. We believe that this constant-pH molecular
      dynamics method, by correctly sampling both charges and conformation, can become
      a valuable help in the understanding of the dependence of protein function and
      stability on pH.

PMID- 9141134
TI  - The reaction pathway of the isomerization of D-xylose catalyzed by the enzyme D
      xylose isomerase: a theoretical study.
AB  - Different pathways of the metal-induced isomerization of D-xylose to D-xylulose
      are investigated and compared in detail using energy minimization and molecular
      dynamics simulation. Two theoretical models are constructed for the reaction: in
      vacuum and in the enzyme D-xylose isomerase. The vacuum model is constructed
      based on the X-ray structure of the active site of D-xylose isomerase. It
      contains the atoms directly involved in the reaction and is studied using a semi
      empirical molecular orbital method (PM3). The model in the enzyme includes the
      effects of the enzyme environment on the reaction using a combined quantum
      mechanical and molecular mechanical potential. For both models, the structures of
      the reactants, products, and intermediate complexes along the isomerization
      pathway are optimized. The effects of the position of the "catalytic Mg2+ ion" on
      the energies of the reactions are studied. The results indicate: 1) in vacuum,
      the isomerization reaction is favored when the catalytic metal cation is at site
      A, which is remote from the substrate; 2) in the enzyme, the catalytic metal
      cation, starting from site A, moves and stays at site B, which is close to the
      substrate; analysis of the charge redistribution of the active site during the
      catalytic process shows that the metal ion acts as a Lewis acid to polarize the
      substrate and catalyze the hydride shift; these results are consistent with
      previous experimental observations; and 3) Lys183 plays an important role in the
      isomerization reaction. The epsilon-NH3+ group of its side chain can provide a
      proton to the carboxide ion of the substrate to form a hydroxyl group after the
      hydride shift step. This role of Lys183 has not been suggested before. Based on
      our calculations, we believe that this is a reasonable mechanism and consistent
      with site-directed mutation experiments.

PMID- 9141135
TI  - Structural change and receptor binding in a chemokine mutant with a rearranged
      disulfide: X-ray structure of E38C/C50AIL-8 at 2 A resolution.
AB  - The characteristic CXC chemokine disulfide core of interleukin-8 (IL-8) has been
      rearranged in a variant replacing the 9-50 disulfide with a 9-38 disulfide. The
      new variant has been characterized by its binding affinity to IL-8 receptors A
      and B and the erythrocyte receptor DARC. This variant binds the three receptors
      with affinities between 500- and 2,500-fold lower than wild-type IL-8. Binding
      affinity results are also reported for the variant with alanine substituted for
      both cysteines 9 and 50. The Glu38-->Cys/Cys50-->Ala IL-8 crystallizes in space
      group P2(1)2(1)2(1) with cell parameters a = 46.4, b = 49.2, and c = 69.5 A, and
      has been refined to an R-value of 19.4% for data from 10 to 2 A resolution.
      Analysis of the structure confirms the new disulfide arrangement and suggests
      that changes at Ile10 may be the principal cause of the lowered affinities.

PMID- 9141136
TI  - Molten globule state of equine beta-lactoglobulin.
AB  - The acid-unfolded state of equine beta-lactoglobulin was characterized by means
      of circular dichroism, nuclear magnetic resonance, analytical gel-filtration
      chromatography, and analytical centrifugation. The acid-unfolded state of equine
      beta-lactoglobulin has a substantial secondary structure as shown by the far
      ultraviolet circular dichroism spectrum but lacks persistent tertiary packing of
      the side chains as indicated by the near-ultraviolet circular dichroism and
      nuclear magnetic resonance spectra. It is nearly as compact as the native
      conformation as shown by the gel filtration and sedimentation experiments, and it
      has the exposed hydrophobic surface as indicated by its tendency to aggregate.
      All of these characteristics indicate that the acid-unfolded state of equine beta
      lactoglobulin is a molten globule state. The alpha helix content in the acid
      unfolded state, which has been estimated from the circular dichroism spectrum, is
      larger than that in the native state, suggesting the presence of nonnative alpha
      helices in the molten globule state. This result suggests the generality of the
      intermediate with nonnative alpha helices during the folding of proteins having
      the beta-clam fold.

PMID- 9141137
TI  - Self-consistent field approach to protein structure and stability. I: pH
      dependence of electrostatic contribution.
AB  - Starting from the simple case of an external field acting on noninteracting
      particles, a formulation of the self-consistent field theory for treating
      proteins and unfolded protein chains with multiple interacting titratable groups
      is given. Electrostatic interactions between the titratable groups are
      approximated by a Debye-Huckel expression. Amino acid residues are treated as
      polarizable bodies with a single dielectric constant. Dielectric properties of
      protein molecules are described in terms of local dielectric constants determined
      by the space distribution of residue volume density around each ionized residue.
      Calculations are based on average charges of titratable groups, distance of
      separation between them, on their pKa's, residue volumes and on the local
      dielectric constant. A set of different residue volumes is used to analyze the
      influence of the permanent dipole of polar parts of the residue on calculated
      titration curves, electrostatic contribution to the free energy of protein
      stability, and pK shifts. Calculations with zero volumes--which means that
      charged portions of protein molecules are viewed as part of the high dielectric
      medium--give good agreement with experimental data. The theory was tested against
      most accurate approaches currently available for the calculation of the pKa's of
      ionizable groups based upon finite difference solutions of the Poisson-Boltzmann
      equation (FDPB). For 70 theoretically calculated pKa's in a total of six proteins
      the accuracy of the approach presented here is assessed by comparison of computed
      pKa's with that measured. The overall root-mean-square error is 0.79, compared to
      the value 0.89 obtained by FDPB approach given in the paper of Antosiewicz et al.
      (J. Mol. Biol. 238:415-436, 1994). The test of Debye-Huckel approximation for the
      electrostatic pair interactions shows that it is in excellent agreement with
      experimental data as well as the calculations of the FDPB and Tanford-Kirkwood
      methods on the pK shifts of His64 in the active site of subtilisin over the whole
      range of ionic strengths. (Gilson and Honig, Proteins 3:32-52, 1988; Russell et
      al., J.Mol.Biol. 193:803-813, 1987). The theory was also analytically and
      numerically tested on a simple models where the exact statistical mechanical
      treatment is still simple (Yang et al., Proteins 15:252-265, 1993; Bashford and
      karplus, J. Phys. Chem. 95:9556-9561, 1991).

PMID- 9141138
TI  - Purification and preliminary crystallographic studies on the sporulation response
      regulatory phosphotransferase protein, Spo0B, from Bacillus subtilis.
AB  - The phosphotransferase protein Spo0B, a component of the sporulation signal
      transduction system in Bacillus subtilis was expressed from the Escherichia coli
      strain BL21DE3. It was purified, crystallized, and 2.25 A data measured using the
      synchrotron source at the Stanford Linear Accelerator Center. The search for
      heavy atom derivatives is in progress.

PMID- 9141139
TI  - Crystallization and preliminary X-ray analysis of the flavoenzyme vanillyl
      alcohol oxidase from Penicillium simplicissimum.
AB  - Vanillyl-alcohol oxidase catalyses the oxidation of several 4-hydroxybenzyl
      alcohols by using 8-alpha-(N3-histidyl)-FAD as a covalently bound prosthetic
      group. Crystals of vanillyl-alcohol oxidase from Penicillium simplicissimum have
      been grown by using the vapor diffusion technique. The space group was found to
      be I, with cell dimensions a = b = 140.5 A, c = 132.9 A. Diffraction data have
      been recorded to 3.2 A resolution by using a laboratory source and to 2.5 A
      resolution on flash freezing the crystal at the ELETTRA Synchrotron X-ray
      diffraction beam line.

PMID- 9141140
TI  - Differences in symptom structure between panic attack and limited symptom panic
      attack: a study using cluster analysis.
AB  - We had investigated the clinical characteristics of panic disorder (PD) in a
      Japanese outpatient population comprised of more than 250 patients diagnosed as
      having PD during a 13-year study period and observed that some PD patients had
      both panic attacks (PA) and limited symptom panic attacks (LPA). In the criteria
      for PD based on the Diagnostic and Statistics Manual of Mental Disorders, third
      edition-revised (DSM-III-R), episodes involving four or more symptoms are
      classified as PA, while those involving fewer than four symptoms are described as
      LPA. Therefore, LPA is identified as part of an episode of PA, since the
      difference between the two episodes is only in the number of symptoms. However,
      some recent research suggests that there is a distinct subgroup of individuals
      who suffer LPA. Using cluster analysis, we investigated the differences between
      PA and LPA groups in terms of the structures of several panic symptoms, which
      included anticipatory anxiety, agoraphobia and 13 clinical symptoms based on the
      DSM-III-R at the time of panic attacks, in 247 patients with PD. Cluster analysis
      revealed clusters of three and four panic symptoms in the PA group and LPA group,
      respectively, and there were also differences in symptom structure between the
      two groups. These results suggest that there may be a subgroup of individuals who
      show LPA among PD patients.

PMID- 9141141
TI  - Abnormal behavior of elderly people residing in institutions of medical and
      social welfare systems.
AB  - We investigated factors correlated with abnormal behavior in the elderly residing
      in a special nursing home (group A) and a psychiatric hospital (group B) using
      the dementia behavior disturbance scale, the mini mental state examination, the
      Japanese version of the Philadelphia Geriatric Center morale scale, and the ADL
      assessment scale. The cognitive function of group B was decreased compared with
      that of group A, but most activities of daily living (ADL) in the latter group
      were disrupted compared with those in the former. Only a few categories of ADL
      correlated with abnormal behavior in group A, whereas cognitive function, quality
      of life, and most categories of ADL correlated with abnormal behavior in group B.
      These results suggest that factors correlated with abnormal behavior in the
      elderly differ within institutions of medical and social welfare systems.

PMID- 9141142
TI  - A study of cognitive development and behavior problems in mentally retarded
      children.
AB  - Cognitive development in seventy-one mentally retarded children (19 autistic, 52
      non-autistic; aged 7-19 years) from a school for handicapped children was
      studied, using Ohta's scale for evaluating cognitive development level based on
      language comprehension (Ohta's stage), and other developmental scales. Behavior
      problems were also examined. The present study reports on the utility of Ohta's
      stage in non-autistic children, and the relationship between cognitive
      development level and behavior problems in mentally retarded children. In non
      autistic children, there were temporal correlations between Ohta's stage and
      other development scales (a standard developmental test, speech development,
      symbolic play development, imitation development), suggesting that in non
      autistic children as well, Ohta's stage may serve well as a scale for cognitive
      development, and reflect symbolic representational functioning. In non-autistic
      children, most behavior problems in feeding, elimination and sleeping,
      hyperkinesis, hypokinesis, stereotyped behaviors, self-injurious behavior and
      licking were closely associated with cognitive development level, and were more
      often noted in children of lower cognitive development level rather than only in
      the severely mentally retarded children. Some behavior problems may often occur
      in the sensorimotor period and hardly occur in the symbolic representational
      period.

PMID- 9141143
TI  - A comparative study of Asperger syndrome with high-functioning atypical autism.
AB  - To test the validity of Asperger syndrome (AS) as defined in ICD-10, 26 patients
      (age range, 3.5 to 12 years) with AS and 16 patients (age range, 3 to 11.5 years)
      with high-functioning (IQ > 90) ICD-10 atypical autism (HAA) were compared on 64
      clinical variables including obstetric risk factors, early developmental
      landmarks, IQ, autistic symptoms on the CARS-TV, epileptic EEG abnormalities and
      epilepsy. AS did not differ significantly from HAA on all but total and four item
      scores (i.e. imitation, visual responsiveness, auditory responsiveness and non
      verbal communication) on the CARS-TV, in which AS scored significantly lower than
      HAA. A discriminant function based on imitation and auditory responsiveness
      predicted 76.2% of the 42 cases. The small difference from HAA indicates that AS
      is better to be regarded as the highest-functioning end of the PDD spectrum,
      rather than a valid subtype of PDD. However, the autistic symptom profile less
      distorted in AS than HAA may warrant a further study on its validity.

PMID- 9141144
TI  - Screening for depression among first-visit psychiatric patients: comparison of
      different scoring methods for the Center for Epidemiologic Studies Depression
      Scale using receiver operating characteristic analyses.
AB  - The present paper aims to compare the ability of eight scoring methods for the
      Center for Epidemiologic Studies Depression Scale (CES-D), one of the most widely
      used self-report inventories for depression, to screen for a major depressive
      episode. The subjects were 591 patients who constituted representative samples of
      the first-visit patients to 23 psychiatric hospitals and clinics all over Japan.
      The criterion diagnoses were given by a semi-structured interview with
      established inter-rater reliability. The eight alternative scoring methods
      included the conventional Likert method, which gives the weights 0, 1, 2 and 3 to
      the four anchor points of the CES-D; the presence method, which gives the weights
      0, 1, 1 and 1, respectively; the GHQ method, which gives the weights 0, 0, 1 and
      1, respectively; the persistence method, which gives the weights 0, 0, 0 and 1,
      respectively; 10-item version, 5-item version, single-item version and the
      algorithmic method. On the basis of the receiver operating characteristic (ROC)
      analyses, it was found that the traditional Likert scoring method of the full CES
      D performed best in detecting major depressive episodes among first-visit
      psychiatric patients. The presence method, the GHQ method and the 10-item version
      appeared to have a similar ability. The persistence method, the 5-item version
      and the single-item version resulted in significantly worse performance.

PMID- 9141145
TI  - The effect of methamphetamine on histamine release in the rat hypothalamus.
AB  - In the present study, the effect of methamphetamine (MAP) on histamine (HA)
      release measured by in vivo brain microdialysis in the rat hypothalamus was
      investigated. Administration of MAP (3 mg/kg) significantly increase HA release
      from 40 to 160 min after the injection. This finding suggests that a moderate
      dose of MAP activates the hypothalamic HA neuron system, which may be related to
      effects of MAP on intrinsic biological rhythms.

PMID- 9141146
TI  - A case of Turner syndrome with schizophrenia: genetic relationship between Turner
      syndrome and psychosis.
AB  - An 82-year-old woman with Turner syndrome and schizophrenia, and her 46-year-old
      daughter with schizophrenia are described. 45X/46XX chromosomal mosaicism was
      identified in the peripheral leukocytes of the mother, who showed several Turner
      dysmorphisms and cavum septi pellucidum in the brain. She had a normal
      reproductive life-span. The daughter resembled the mother in terms of
      schizophrenic symptoms, but she did not show any signs of Turner dysmorphism or
      chromosomal abnormality. The phenotype-karyotype relationship of Turner syndrome
      and the genetic relationship with psychosis are discussed.

PMID- 9141147
TI  - Central mediation of the effects of interleukin-1 on social exploration and body
      weight in mice.
AB  - To study the role of central IL-1 receptors in the effects of recombinant human
      IL-1 beta (IL-1 beta) on behavior and body weight, intracerebroventricular
      (i.c.v.) injection of the specific antagonist of IL-1 receptors, IL-1ra, was
      administered to mice injected intraperitoneally (i.p.) and i.c.v. with various
      doses of IL-1 beta. Doses of 500 ng i.p. IL-1 beta and 900 pg i.c.v. IL-1 beta
      induced a comparable decrease in social behavior and loss of body weight.
      Pretreatment with IL-1ra (1.8 micrograms/mouse, i.c.v.) blocked the effects of
      i.c.v. IL-1 beta (900 pg/mouse) on social behavior. i.c.v. IL-1ra (3.6
      micrograms/mouse) also attenuated the effects of i.p. IL-1 beta (500 ng/mouse) on
      social behavior and change in body weight, suggesting that the effects of
      peripheral IL-1 beta are centrally mediated.

PMID- 9141148
TI  - Sustained elevation of vasopressin plasma levels in healthy young men, but not in
      abstinent alcoholics, upon expectation of novelty.
AB  - The role of vasopressin (AVP) as a stress hormone in man is still a matter of
      controversy. Thus, the response of plasma AVP, among other hormones, to either
      intravenously injected human corticotropin releasing factor (hCRF, in the absence
      or presence of the opioid antagonist naloxone) or a combined 5-minute stress test
      was compared in healthy men (n = 10) and short-term abstinent alcoholics (n =
      11), a group with recognized abnormalities of humoral stress parameters. Stimuli
      were applied blindly and in random order, one per day, in a 3-day experimental
      block. A second block using the same standardized protocol was carried out 12
      weeks later. Alcoholics entered block I 8 days after the last ethanol ingestion.
      Up to block II, they were strictly controlled for abstinence. On each
      experimental day, subjects remained supine from 0700h until 1500h. Stimuli were
      applied alternatively at 1030h each day. Fourteen blood samples were drawn per
      day with simultaneous fluid substitution. There were no significant changes in
      plasma AVP as an acute response to any of the stimuli in either group or block.
      However, unexpectedly, controls had significantly higher basal AVP levels
      throughout block I as compared with block II without concomitant changes in
      plasma osmolality or blood pressure. Further analysis of the data revealed that
      the dramatically increased AVP levels of the five younger control subjects
      accounted for this difference. In fact, AVP levels in the five older healthy
      subjects and in all alcoholics remained low throughout the two blocks. Our data
      suggest that plasma AVP is continuously elevated in healthy young men upon
      anticipation of novelty. In contrast, healthy men of the older age group and
      early abstinent alcoholics seem to lack such a sustained AVP response.

PMID- 9141149
TI  - Reduced benzodiazepine sensitivity in patients with premenstrual syndrome: a
      pilot study.
AB  - Premenstrual syndrome (PMS) is characterized by cyclical changes in psychological
      and physical symptoms related to the formation of the corpus luteum and the
      fluctuations of gonadal hormones. Ovarian steroids have direct effects on
      neurotransmission, exemplified by the binding of certain metabolites of
      progesterone to the gamma-amino-butyric acid (GABAA) receptor where they exert a
      facilitating effect on inhibitory neurotransmission. There is also evidence for
      steroids with inverse-agonist actions on the GABAA-receptor with opposite effects
      on the GABAergic transmission. The purpose of this pilot study was to examine a
      possible decrease in GABAA/benzodiazepine-receptor sensitivity in PMS patients
      using saccadic eye velocity and self-ratings of sedation as dependent measures.
      Seven patients with proven PMS and seven control subjects were recruited for the
      study. Saccadic eye velocity (SEV) and visual analogue ratings for sedation and
      mood were measured after increasing doses of placebo and diazepam. The PMS
      patients responded with a significantly less decrease in saccadic eye velocity
      after benzodiazepine injections compared with control subjects, the difference
      being most prominent in the luteal phase. This group difference was due to an
      increased SEV responsiveness to benzodiazepines among control subjects in the
      luteal phase compared with the follicular phase. The PMS patients in the luteal
      phase responded with less increase in sedation change scores following
      benzodiazepine injections compared with control subjects. This group difference
      in the luteal phase was due to a decreased sedation response to benzodiazepines
      across the menstrual cycle in the PMS patients. There was no correlation between
      sedation change scores and SEV in PMS patients. These results support evidence
      for a reduced or dysregulated sensitivity at the GABAA/ benzodiazepine-receptor
      complex in patients with PMS.

PMID- 9141150
TI  - Restoration of detectable melatonin after entrainment to a 24-hour schedule in a
      'free-running' man.
AB  - We evaluated a 37-year-old male with a non-24-h sleep-wake disorder. His
      environment gave him little exposure to bright light. Circadian profiles of
      temperature, melatonin, thyrotropin, cortisol and testosterone were obtained
      along with endocrine challenges of the thyroid, adrenal, growth hormone and
      gonadal axes. Multiple endocrine abnormalities were detected. Testosterone was
      low and nocturnal thyrotropin levels were erratic. Serum melatonin was
      undetectable throughout the day and night on multiple occasions, and responses to
      infusions of TRH, GnRH and GRF-44 were abnormal. Responses to CRH infusion were
      normal. The patient was successfully entrained to a 24-h schedule by daily
      exposure to 2500 lux light from 0700h to 0900h, avoidance of light (by wearing
      dark goggles) from 1800h to 2300h, and strict enforcement of a dark environment
      from 2300h to 0700h. After entrainment, a normal pattern of nocturnal melatonin
      secretion was found. GH response to GRF-44 also normalized, although abnormal
      responses to TRH and GnRH persisted. This case raises the possibility that a
      complex interaction of light exposure with the circadian system can reversibly
      suspend pineal gland secretion of melatonin indefinitely. It also suggests that
      circadian rhythm disorders be considered in the differential diagnosis of
      abnormal endocrine function.

PMID- 9141151
TI  - Lack of pineal beta-adrenergic receptor alterations in suicide victims with major
      depression.
AB  - Noradrenergic function may be altered in depressive illness and thereby
      contribute to decreased pineal production of melatonin levels, as previously
      described in some depressed subjects. In the present study, the hypothesis was
      tested that pineal beta-adrenergic binding would be increased in persons
      committing suicide with evidence of depressive disorders, reflecting diminished
      noradrenergic input. Initially, post-mortem human pineal glands were obtained at
      autopsy. Diagnostic and symptomatic information was then systematically collected
      from family members using standardized interview techniques. Seven subjects who
      committed suicide and suffered from major depression, and without exposure to
      treatment for depressive symptoms were age- and sex-matched with control
      subjects. Pineal beta-adrenergic binding was assessed by quantitative
      autoradiography employing four concentrations of [125I]pindolol. Because of
      possibly complex adrenergic regulation of the pineal, beta-adrenergic receptor
      binding were subtyped using the selective blocker ICI 89406. No differences in
      beta-adrenergic receptors were detected between subjects with major depression
      compared to the matched controls.

PMID- 9141152
TI  - The ILCOR advisory statements. International Liaison Committee on Resuscitation.

PMID- 9141153
TI  - Advisory statements of the International Liaison Committee on Resuscitation
      ('ILCOR').

PMID- 9141154
TI  - Single rescuer adult basic life support. An advisory statement from the Basic
      Life Support Working Group of the International Liaison Committee on
      Resuscitation (ILCOR)

PMID- 9141155
TI  - The Universal ALS algorithm. An advisory statement by the Advanced Life Support
      Working Group of the International Liaison Committee on Resuscitation.

PMID- 9141156
TI  - Early defibrillation. An advisory statement by the Advanced Life Support Working
      Group of the International Liaison Committee on Resuscitation.

PMID- 9141157
TI  - Paediatric life support. An advisory statement by the Paediatric Life Support
      Working Group of the International Liaison Committee on Resuscitation.
AB  - This document reflects the deliberations of ILCOR. The epidemiology and outcome
      of paediatric cardiopulmonary arrest and the priorities, techniques and sequence
      of paediatric resuscitation assessments and interventions differ from those of
      adults. The working group identified areas of conflict and controversy in current
      paediatric basic and advanced life support guidelines, outlined solutions
      considered and made recommendations by consensus. The working group was surprised
      by the degree of conformity already existing in current guidelines advocated by
      the American Heart Association (AHA), the Heart and Stroke Foundation of Canada
      (HSFC), the European Resuscitation Council (ERC), the Australian Resuscitation
      Council (ARC), and the Resuscitation Council of Southern Africa (RCSA).
      Differences are currently based upon local and regional preferences, training
      networks and customs, rather than scientific controversy. Unresolved issues with
      potential for future universal application are highlighted. This document does
      not include a complete list of guidelines for which there is no perceived
      controversy and the algorithm/decision tree figures presented attempt to follow a
      common flow of assessments and interventions, in coordination with their adult
      counterparts. Survival following paediatric prehospital cardiopulmonary arrest
      occurs in only approximately 3-17% and survivors are often neurologically
      devastated. Most paediatric resuscitation reports have been retrospective in
      design and plagued with inconsistent resuscitation definitions and patient
      inclusion criteria. Careful and thoughtful application of uniform guidelines for
      reporting outcomes of advanced life support interventions using large,
      randomized, multicenter and multinational clinical trials are clearly needed.
      Paediatric advisory statements from ILCOR will, by necessity, be vibrant and
      evolving guidelines fostered by national and international organizations intent
      on improving the outcome of resuscitation for infants and children worldwide.

PMID- 9141158
TI  - Special resuscitation situations. An advisory statement on conditions which may
      require modifications in resuscitation procedures or techniques. Prepared by
      members of the International Liaison Committee on Resuscitation.

PMID- 9141159
TI  - Recommended guidelines for reviewing, reporting, and conducting research on in
      hospital resuscitation: the in-hospital 'Utstein style'. A statement for
      healthcare professionals from the American Heart Association, the European
      Resuscitation Council, the Heart and Stroke Foundation of Canada, the Australian
      Resuscitation Council, and the Resuscitation Councils of Southern Africa.

PMID- 9141160
TI  - Studying the quality of life after organ transplantation: research problems and
      solutions.
AB  - Studies assessing the quality of life after organ transplantation proliferated in
      the 1980s after improved immunosuppression led to higher survival rates. Despite
      severe critiques of the methods employed in this research, as well as more
      general criticisms of the financial motives behind it, medical journals have
      continued to publish reports which almost uniformly conclude that transplant
      recipients enjoy a high quality of life. This paper revisits the critiques, asks
      why they have had so little impact, and suggests a new approach.

PMID- 9141161
TI  - Kidney failure and transplantation in China.
AB  - The incidence of chronic renal failure in China is approximately 120,000 cases
      per year; the vast majority of these new cases will die within a very short time
      because of the shortage of funds, dialysis machines, and organs for
      transplantation. This paper focuses on the reasons behind the organ shortage and
      the strategies proposed by the Chinese medical profession to increase the supply
      of transplantable kidneys. The data were gathered on multiple trips to China,
      Hong Kong and Taiwan between August 1993 and January 1995. During these trips the
      author spoke formally with nephrologists, urologists, dialysis and transplant
      nurses, and other individuals active in the field of organ procurement, and
      informally with others familiar with general hospital practice. The author also
      draws heavily on articles published in leading Chinese journals. The kidney
      shortage in China is produced by the same sorts of problems as exist in other
      countries, but the shortage is aggravated by certain beliefs and practices
      specific to Chinese populations. Live donation is hampered by traditional beliefs
      about the function of the kidney, while cadaver donation is hampered by
      reluctance to cut a body and a host of beliefs about ghosts, labeled "feudal
      superstitions" by the authorities. Cadaver donation is further restrained by the
      lack of legal recognition of "brain death". In response to the organ shortage,
      the Chinese medical community has expanded the range of eligible sources to
      include those condemned to death as criminals, a practice itself usually
      condemned by the wider international community. At the same time it has
      advocated: (1) enhancing corpse donation through propaganda work, administrative
      work, legal work, and incentives; (2) encouraging live donation; (3)
      familiarizing the public with the benefits of organ transplantation, and (4)
      pursuing the development of artificial organs.

PMID- 9141163
TI  - Effectiveness of condoms in preventing HIV transmission.
AB  - The consistent use of latex condoms continues to be advocated for primary
      prevention of HIV infection despite limited quantitative evidence regarding the
      effectiveness of condoms in blocking the sexual transmission of HIV. Although
      recent meta-analyses of condom effectiveness suggest that condoms are 60 to 70%
      effective when used for HIV prophylaxis, these studies do not isolate consistent
      condom use, and therefore provide only a lower bound on the true effectiveness of
      correct and consistent condom use. A reexamination of HIV seroconversion studies
      suggests that condoms are 90 to 95% effective when used consistently, i.e.
      consistent condom users are 10 to 20 times less likely to become infected when
      exposed to the virus than are inconsistent or non-users. Similar results are
      obtained utilizing model-based estimation techniques, which indicate that condoms
      decrease the per-contact probability of male-to-female transmission of HIV by
      about 95%. Though imperfect, condoms provide substantial protection against HIV
      infection. Condom promotion therefore remains an important international priority
      in the fight against AIDS.

PMID- 9141162
TI  - Changing patterns of pharmaceutical practice in the United States.
AB  - In the United States, contradictions related to medicine use abound in a social
      environment in which the pursuit of health has become a cultural project. In a
      marketplace where over half a million health products are available, choices at
      once seem to foster agency and encourage dependency on medical fixes. The
      aggressive marketing of medicines as indispensable commodities co-exits with
      rising concerns among the lay population about what is safe in the short- and
      long-term. In this paper we broadly consider medication-related practice in the
      United States as it is affected by social, cultural, and political-economic
      factors. We direct attention to changes in medicine use related to product
      proliferation, lowered thresholds of discomfort, the economics of health care,
      and a revival of the self-help ethic. We also consider the manner in which the
      demand for and use of medications reflect deeply embedded cultural ideals and
      emergent perceptions of need. We juxtapose two trends in American thinking about
      medicines: (1) the perception that "more is better," associated with cultural
      impatience with illness; and (2) a growing doubt about medicine necessity,
      safety, and efficacy.

PMID- 9141164
TI  - After unification: gender and subjective health status in East and West Germany.
AB  - Results of a random survey of 2574 adults in East and West Germany in 1992 show
      virtually no differences in subjective health status for the populations of East
      versus West Germany and only slight differences for men versus women. A closer
      analysis via multiple regression indicates, however, that contrary to previous
      results from other countries West German women have a better health status than
      men. Of the four gender groups analyzed separately East German men are the best
      off, while owing to a number of socio-economic status discrepancies, East German
      women report the worst health status. Surprisingly, West German men show a poorer
      subjective health status than East German men, although a number of factors like
      participation in sport, better income and younger age would predict otherwise. It
      is suggested that their health situation is negatively influenced not only by
      their work situation but also by outside private commitments not accounted for in
      this analysis. Also difficult to explain from the present data is the relatively
      good health status of East German men. Despite an insecure job and a difficult
      work situation they may experience unification in sociopolitical terms and their
      present social status as something positive. Overall, conditions in the system of
      West Germany show a tendency to favor women, while those in East Germany clearly
      favor men.

PMID- 9141166
TI  - Nonconventional medicine in Israel: consultation patterns of the Israeli
      population and attitudes of primary care physicians.
AB  - This paper reports the findings of a study of nonconventional medicine in Israel.
      Data regarding patterns and correlates of consultations with alternative medicine
      practitioners were obtained from structured face-to-face interviews with a
      representative sample of 2030 Jewish adults aged 45 to 75. In addition, in-depth
      open-ended interviews were conducted with a convenience sample of 20 primary care
      physicians in order to explore their beliefs, attitudes and behaviors regarding
      nonconventional medicine. Six percent of the respondents interviewed in the
      population study visited an alternative practitioner in the year prior to the
      interview. For most of them, the consultation was a consequence of disappointment
      with the lack of success of conventional medical treatment. Most felt that the
      alternative medicine treatment had helped. Nearly 40% were seeing their regular
      primary care physician at the same time as they were seeing an alternative
      medical practitioner. Women were more likely than mean to consult an alternative
      medicine practitioner; consulters rated their health status more negatively than
      non-consulters. Consulters had a higher level of education than non-consulters,
      but the two groups did not differ in terms of age or economic status. Nearly all
      of the physicians stated that they refer patients to alternative practitioners;
      in most cases, the referrals are in response to patients' requests. Although
      skeptical of the scientific basis of alternative medicine therapies, most of the
      physicians believed that some therapies, even if only because of the "placebo
      effect", were effective in some cases. Almost all felt that the Ministry of
      Health, which today does not recognize any form of alternative medicine, should
      establish control over the training and practice of alternative medical
      practitioners. The findings from both parts of the study suggest that patients
      and primary care physicians in Israel do not view nonconventional medicine as a
      threat to conventional medicine, but rather as complementary to it.

PMID- 9141165
TI  - Understanding the variability in the effectiveness of community heart health
      programs: a meta-analysis.
AB  - Over the past 25 years, community interventions to reduce cardiovascular disease
      (CVD) have been conducted around the world with very mixed results. This study
      uses meta-analysis to assess whether the variation in the observed effectiveness
      of community heart health programs (CHHP) is related to characteristics of the
      intervention program, the population under study, or the evaluation methods. A
      CHHP is defined as any primary prevention program that attempted to reduce the
      population burden of CVD by shifting the distribution of risk factors in a
      general population. To be included in the meta-analysis, a study must have
      utilized a reference group in the evaluation, employed a repeated independent
      cross-sectional measurement design, and reported sufficient outcome information
      for at least one of four major risk factors: smoking, total cholesterol, blood
      pressure, and body weight. Results of these studies are summarized with the
      effect size measure (Yi1-Yi2)-(Yr1-Yr2)Sr1 where Y = outcome measure, S =
      standard deviation of the outcome measure, 1 = baseline, 2 = follow-up. i =
      intervention, and r = reference community. This measure, which reports the net
      change in the intervention group in terms of the variability in the reference
      population before the start of the intervention, permits comparison across
      different outcome measures and facilitates the aggregation of effects across
      studies. Generalized least squares regression, which permits the incorporation of
      multiple, dependent effect sizes from a single study, was used to assess the
      impact of characteristics of the intervention (prevention strategy, type of mass
      communication, community organization, and environmental change), the population
      (setting, gender, year of follow-up measurement), and the evaluation design and
      implementation (the number of communities, matching of communities, the follow-up
      time, the response rate, and covariate adjustment in the analysis) on the effect
      sizes. The results of this analysis suggest that the characteristics of the
      evaluation method account for much of the heterogeneity in the outcome of CHHPs,
      though some intervention characteristics also play a role.

PMID- 9141167
TI  - The socio-economic distribution of heart diseases: changing gradients in The
      Netherlands.
AB  - Two different Dutch data-sets were used to examine trends in the association
      between socio-economic characteristics and the risk of heart disease. Data of the
      Dutch Quality of Life Surveys allowed the examination of trends in the
      association between educational level and self-reported heart disease during the
      period 1974-1993. For both the general Dutch population and the subpopulation of
      men aged 40 years and older, we found an inverse gradient during the whole
      period. The gradient climaxed at 1980-1983, and narrowed afterwards. Furthermore,
      ecological analyses, relating regional mean personal incomes to regional directly
      standardised mortality rates of coronary heart diseases (CHD) and all heart
      diseases, showed similar patterns of social differentials. The findings suggest
      that, in the Netherlands, there is a narrowing gradient of the association
      between socio-economic characteristics and heart disease in the late eighties and
      early nineties.

PMID- 9141168
TI  - The impact of anomia as a factor in a demand resource model of health.
AB  - The particular aim of the present study was to explore the interrelations between
      the construct of anomia, conceptualized as internal health demand or resource,
      and self-reported ill-health in the framework of a demand resource model. The
      four main constructs of this model were considered as recursive causal levels:
      (1) socio-economic data, (2) external resources/demands, (3) internal resources/
      demands, and (4) ill-health. Study statistics comprised graphical models to
      reveal the relations between variables using the statistical program DIGRAM
      designed for discrete graphical models. This method of data analysis permits a
      focus on the link between anomia and the other three levels. The function of
      anomia as an intermediate data level which might prove to be an intervening
      variable can be evaluated. A total of 440 subjects of a random community sample
      were included in the final analysis. In the framework of a demand resource model,
      it was possible to confirm that the construct of anomia plays a key role in
      health outcome. Graphical models showed that a low degree of anomia is related to
      high psychological quality of life and few psychosomatic symptoms on the one
      hand, and to good social integration and emotional support, a low amount of daily
      hassles and high educational level on the other hand. As an overall conclusion,
      it can be stated that the evaluation by the graphical modeling procedure permits
      a good fit of theory with methods.

PMID- 9141169
TI  - Pregnancy and addiction: translating research into practice.
AB  - In some areas of the United States pregnant women are incarcerated if they are
      addicted to illegal substances, particularly crack cocaine. However,
      incarceration does not happen to all pregnant addicts, but instead reflects
      racial/ethnic and socioeconomic categories of prejudice. In the following
      article, the authors suggest that analysis of this pattern of incarceration is
      clarified by the use of critical medical anthropology perspective with its
      explicit historical, political and economic foci. In addition, the authors
      introduce a program for addicted women that incorporates into practice the
      findings of the initial research and demonstrates how research can be translated
      into practice.

PMID- 9141170
TI  - Anthropological research and the politics of HIV prevention: towards a critique
      of policy and priorities in the age of AIDS.
AB  - This paper is based on the author's ethnographic HIV prevention research at a
      community-based residence for women in New York City who have a history of
      homelessness and diagnosis of mental illness. The author presents the human face
      of this American tragedy, while exploring the ways in which larger social forces
      circumscribe these women's lives. The author also critically assesses the HIV
      prevention agenda, including the dominant paradigm in prevention intervention.
      Despite acceptance by the most prominent players in AIDS prevention in the United
      States, the most popular prevention theories are theoretically and substantively
      inadequate. While educational interventions and behavior change efforts may have
      some impact on inhibiting HIV transmission, the focus on the individual as the
      sole locus of change tends to obscure the social and material factors in the
      spread of the disease. An anthropologically informed alternative, integrating
      social responsibility and social justice, is explored. Also considered are
      dilemmas in applying anthropology to AIDS prevention research and how to
      translate theoretical abstractions into humane and pragmatic social programs.

PMID- 9141171
TI  - Clearing the air: challenges to introducing smoking restrictions in West
      Virginia.
AB  - One of the most fundamental rights, the right to breathe air free of unhealthy
      carcinogens, is continuously threatened by powerful corporate tobacco interests,
      which spend enormous amounts of money not only to promote smoking, but also to
      stifle local, state, and national efforts to control smoking in the United
      States. From the perspective of a "committed participant" this paper discusses
      recent difficulties encountered in attempting to introduce West Virginia's first
      comprehensive smoking control legislation, and the strategies used to overcome
      them. The primary message reported here is that, given the overwhelming
      financial, emotional, and human-potential costs involved in ongoing tobacco abuse
      in the United States, it is essential that citizens unite to protect the health
      of all children and the vast majority of adults who do not smoke, and to
      discourage the consumption of cigarettes, the single biggest cause of disease and
      death in our society. The example reported here from West Virginia demonstrates
      that persistent citizen activism can make a critical difference in promoting laws
      that protect human health from unhealthy environmental tobacco smoke.

PMID- 9141172
TI  - Working from the inside out: implications of breast cancer activism for
      biomedical policies and practices.
AB  - Much has been written about women with breast cancer: about women's lifestyles
      and reproductive strategies as possible risk factors for the disease, factors
      which impede or facilitate women's participation in mammography screening, ways
      to involve women in treatment decision-making, and women's ability to cope with
      breast cancer diagnoses. Seldom do these accounts examine breast cancer from the
      perspective of women with the disease. This essay presents material from an
      ethnographic study in the United States to explore the ways that women have come
      forward as informed consumers and activists working to make biomedical practices
      more responsive to the needs of women with breast cancer. Insofar as breast
      cancer activists reflect the concerns of a predominantly white, middle class
      constituency, however, additional questions are raised concerning their
      constructions of breast cancer and the problematics of treatment.

PMID- 9141173
TI  - Politicizing abortion: personal morality and professional responsibility of
      residents training in the United States.
AB  - Ever-increasing technological innovations surrounding birth are creating new
      challenges in biomedical ethics in U.S. obstetrics. The politicization of
      abortion has augmented these challenges and led to increased conflict between
      physicians' personal morality and professional responsibility. This paper focuses
      on some of the problems generated by abortion policies and procedures in an
      obstetric/ gynecology residency program. Examples of conflicts among residents
      are presented to demonstrate the effect of pluralistic moral perspectives. A
      system is described where some residents will do abortions and some will not.
      Patients seeking abortion are often treated in an unprofessional manner when it
      appears that a conflict exists between the values of patients and those of
      residents. Unless the socialization of residents includes ethical training,
      defined educational policy and institutional direction, ethical dilemmas will
      lead to increased resident stress, an inadequate doctor-patient relationship and
      a continued shortage of physicians willing to perform abortions despite new
      policies called for in graduate medical education.

PMID- 9141174
TI  - Firearm suicide among older women in the U.S.
AB  - Contrary to the common view that older women (65+) in the United States use
      suicide methods that have relatively low potential for death, firearms have
      become the most common suicide method in this group. The present study examines
      the association between demographic and geographic factors and the use of
      firearms vs other suicide methods. Data were derived from the National Center for
      Health Statistics (NCHS) Mortality Detail Files (1989-1991). Results from a
      logistic regression analysis indicate that among white women 65 and over who died
      by suicide in 1989-1991, the risk of using firearms varied significantly across
      demographic and geographic subcategories of the population. The following
      characteristics among women were significantly more likely to be associated with
      the use of firearms as a suicide method: ages 65-74, married, of lower
      educational attainment, in nonmetropolitan areas, and in the South. Research is
      needed to assess the effects of limiting firearms on the growing proportion of
      firearm-related suicides among older women.

PMID- 9141176
TI  - The use of bibliometric data in evaluating research on therapeutic community for
      addictions and in psychiatry.
AB  - The purpose of this study is to describe the publication characteristics
      associated with therapeutic community research and illustrate differences between
      addiction studies and other types of therapeutic community papers. A total of 223
      published reports on research pertaining to the therapeutic community in a
      variety of treatment settings from 1987 to 1992 were analyzed. The articles
      consisted mainly of addiction studies (38%) and hospital psychiatry (36%)
      studies. Collaborative authorship was scanty. Quantitative studies (systematic
      data presented and analyzed statistically) were performed more often in addiction
      papers than in psychiatric therapeutic community papers. Addiction studies were
      also cited slightly more often. Addictions are often a rather simple and distinct
      focus for research, as well as a major public health problem. This may lead to
      the smoother use of traditional quantitative research strategies and standard
      publication channels than in other psychiatric therapeutic community studies.

PMID- 9141175
TI  - Perceived effectiveness of community-based measures against alcohol misuse among
      "problem" and "nonproblem" drinkers.
AB  - Perceptions of the effectiveness of 11 measures against alcohol misuse were
      examined in a community survey. School-based programming was most often and
      increased alcohol taxation least often rated effective. Binge drinking in the
      past year and male gender were inversely associated with perceived effectiveness,
      particularly of countermeasures with direct personal impact, including stricter
      enforcement of laws against driving while intoxicated and increased taxation.
      Studies of support for alcohol control have reported similar relationships
      between drinking behavior and support for measures imposing personal
      restrictions. Perceived effectiveness and support thus appear to be related yet
      distinct constructs. Improved understanding of the interrelationships among
      perceived effectiveness, support, drinking behavior, and empirically demonstrated
      effectiveness of countermeasures may aid in identifying strategies which are both
      effective and acceptable to targeted populations.

PMID- 9141177
TI  - Job dissatisfaction and substance use among employed high school students: the
      moderating influence of active and avoidant coping styles.
AB  - This study extends prior stress-coping-substance use research among adolescents
      by examining the employment context. Specifically, this study examines the
      relation of job dissatisfaction to substance use and the potential moderating
      influence of active and avoidant coping styles. Data were obtained from 446
      employed high school students. Ordered-probit regression analyses reveal that job
      dissatisfaction is positively related to cigarette and alcohol use, but not to
      illicit drug use. Coping styles do not moderate the relation between job
      dissatisfaction and substance use. Nonetheless, coping styles have significant
      main-effect relations to substance use. Active coping is negatively related and
      avoidant coping is positively related to both cigarette and alcohol use. Neither
      coping style is related to illicit drug use.

PMID- 9141178
TI  - Validation of a measure of excessive drinking: frequency per year that BAL
      exceeds 0.08%.
AB  - Although self-report data are generally evaluated as reliable, validity estimates
      for self-reported drinking behavior are not as favorable. A new method of
      measurement addressing problems currently associated with the questionable
      validity of self-report drinking information is introduced. Study 1 tests the
      correspondence between the new measure (occasions per year blood alcohol level
      exceeded 0.08%), traditional self-report measures, and laboratory alcohol
      consumption. The novel measure correlated most strongly with volume of alcohol
      consumed in the laboratory compared to the traditional measures. In Study 2 the
      novel measure was favored over a traditional measure when discriminating between
      the presence and absence of problem-drinking symptoms.

PMID- 9141179
TI  - Correlates of change in adolescent alcohol consumption in Ireland: implications
      for understanding influences and enhancing interventions.
AB  - Studies of two similar cohorts of students in Ireland in 1984 and 1992 showed a
      dramatic increase in the consumption of alcohol, especially in the frequency with
      which students reported being drunk. A comparison of measures obtained at both
      times showed that there were major changes with regard to beliefs about
      consequences of alcohol consumption in a direction favorable to consumption as
      well as increases in the perceived social support for drinking. However, there
      were no strong indications that changes in problem behavior were associated with
      the observed increases in drinking patterns. These results are supportive of some
      explanatory models of initiation to substance use and have associated
      implications for programs designed to reduce consumption.

PMID- 9141180
TI  - Recovery: with and without self-help.
AB  - Although self-help/mutual-help groups, like Alcoholics Anonymous, are important
      factors in the recovery of many chemically dependent individuals, the large
      dropout rates from such groups and the awareness that many who drop out do not
      return to dependent behavior raises interesting questions about other paths to
      sustained abstinence and recovery. Current emphasis on treatment outcome studies
      provides a means for researching factors in both those who recover with and
      without the assistance of self-help/mutual-help groups. The authors suggest some
      questions which might be investigated.

PMID- 9141181
TI  - The rules of drug taking: wine and poppy derivatives in the ancient world. V.
      Sobriety or postponement of drunkenness?
AB  - In spite of declared intentions to maintain control of drinking, we have cues
      that during the symposium enough wine was ingested to get intoxicated. Hence, it
      was widely debated how much wine could be safety drunk, and the conclusion was
      that it was a matter of individual endurance. Apparently, elders were less prone
      to wine-induced loss of rationality and control. In conclusion, the Ancients were
      aware of potential dangers of wine and that its consumption needed rules, but
      apparently these rules existed for being broken.

PMID- 9141183
TI  - Salmonella invasion and delivery of protein effectors to mammalian cell
      cytoplasm.

PMID- 9141184
TI  - Establishing communication via gram-negative bacterial pili.

PMID- 9141185
TI  - The chain of command in Pseudomonas quorum sensing.

PMID- 9141182
TI  - Influence of interpersonal and mass-mediated interventions on injection drug and
      crack users: diffusion of innovations and HIV risk behaviors.
AB  - Evaluation research of public health media campaigns to influence behavior change
      often bemoans the lack of relevance to target audience and an absence of
      integrated interpersonal and mass-mediated communication channels. The assumption
      that illegal drug users are disconnected from mass-mediated communication may
      account for this absence of media interventions. The authors used cross
      tabulation, chi-square, and regression analyses to demonstrate that many out-of
      treatment drug users in an HIV-prevention research project are media consumers
      and that participants who recalled seeing or hearing media interventions reported
      greater levels of positive behavior change than participants who did not recall
      such messages. Results suggest coordination of human and mass-mediated public
      health messages relevant to this population to facilitate behavior changes.

PMID- 9141186
TI  - Year of the genome.

PMID- 9141187
TI  - A paradigm for virus-induced demyelinating disease.

PMID- 9141188
TI  - Viral manipulations of the actin cytoskeleton.
AB  - Viruses succeed as intracellular parasites because of their ability to invade
      cells and appropriate the cellular machinery required during their life cycle.
      The actin cytoskeleton of the host cell does not escape viral infection
      unscathed, but is often co-opted by the virus at many different stages of its
      life cycle to facilitate the infection process.

PMID- 9141189
TI  - Type III secretion systems: machines to deliver bacterial proteins into
      eukaryotic cells?
AB  - Type III secretion systems in certain bacterial pathogens are induced upon
      contact with host cells and directly deliver virulence proteins into the host
      cell cytosol. The increasing number of Gram-negative bacterial pathogens
      discovered to encode type III secretion systems raises interesting questions. Are
      type III systems generic machines that deliver virulence proteins into host
      cells? Is contact with host cells a common regulatory cue for type III systems?

PMID- 9141191
TI  - The evolution of epidemic Vibrio cholerae strains.
AB  - The emergence of the novel Vibrio cholerae strain, O139 Bengal, which caused a
      large epidemic in Southeast Asia, underlines the adaptability of pathogenic
      microorganisms. Recent studies reveal that horizontal transfer of cell-wall
      polysaccharide genes played a central role in the emergence of this strain and
      that its genesis may not be as unique as initially believed.

PMID- 9141190
TI  - Bacterial phospholipases and their role in virulence.
AB  - Virulence of many bacterial pathogens is based, at least in part, on the action
      of phospholipases. The consequences may be immediate and direct, as in the action
      of Clostridium perfringens alpha toxin on red cells or platelets, or subtle, as
      with phosphatidylinositol-specific phospholipases of Listeria monocytogenes and
      other bacteria.

PMID- 9141192
TI  - Calcium channels prove to be a real headache.

PMID- 9141193
TI  - The 'sniffer-patch' technique for detection of neurotransmitter release.
AB  - A wide variety of techniques have been employed for the detection and measurement
      of neurotransmitter release from biological preparations. Whilst many of these
      methods offer impressive levels of sensitivity, few are able to combine
      sensitivity with the necessary temporal and spatial resolution required to study
      quantal release from single cells. One detection method that is seeing a revival
      of interest and has the potential to fill this niche is the so-called 'sniffer
      patch' technique. In this article, specific examples of the practical aspects of
      using this technique are discussed along with the procedures involved in
      calibrating these biosensors to extend their applications to provide
      quantitative, in addition to simple qualitative, measurements of quantal
      transmitter release.

PMID- 9141194
TI  - Neurotrophins and activity-dependent plasticity of cortical interneurons.
AB  - Neocortical and hippocampal GABA-containing interneurons are susceptible to
      activity-dependent modulation, such as regulation of soma size, numbers of
      synaptic contacts, and levels of GABA or neuropeptide expression. In vitro, the
      effects of neuronal activity on morphology and gene expression of GABA-containing
      neurons are mimicked, in part, by members of the neurotrophin gene family, such
      as brain-derived neurotrophic factor (BDNF). In the neocortex and hippocampus,
      BDNF is synthesized and secreted in an activity-dependent manner by pyramidal
      neurons, the target cells of GABA-containing neurons, suggesting that BDNF is an
      activity-dependent, target-derived trophic factor for these interneurons. In
      support of this, neuronal activity fails to upregulate the expression of
      neuropeptide Y in hippocampal cultures from BDNF-deficient mice. We, therefore,
      hypothesize that neurotrophins might mediate some of the actions of neuronal
      activity on GABA-containing neurons.

PMID- 9141195
TI  - Do multilineage potential neural stem cells really exist in the brain of adult
      mammals.

PMID- 9141197
TI  - The functional neuroanatomy of episodic memory.
AB  - Functional neuroimaging studies have revealed that effective encoding in episodic
      memory is associated with enhanced activity in left prefrontal cortex, whereas
      retrieval is accompanied by the enhancement of predominantly right-sided
      prefrontal activity. The extent of the contribution of prefrontal cortex to
      episodic memory, and the fact that the encoding and retrieval operations it
      supports are differentially lateralized, were unexpected on the basis of evidence
      from lesion studies. Such studies have highlighted the crucial role in episodic
      memory played by the hippocampus and related medial temporal lobe structures.
      Neuroimaging studies, however, have had only limited success in elucidating the
      role of the hippocampus in episodic memory. Refinements in experimental design
      and improved spatial resolution should promote rapid future progress with respect
      to this issue.

PMID- 9141196
TI  - Presynaptic inhibition of elicited neurotransmitter release.
AB  - Activation of presynaptic receptors for a variety of neurotransmitters and
      neuromodulators inhibits transmitter release at many synapses. Such presynaptic
      inhibition might serve as a means of adjusting synaptic strength or preventing
      excessive transmitter release, or both. Previous evidence showed that presynaptic
      modulators inhibit Ca2+ channels and activate K+ channels at neuronal somata.
      These modulators also inhibit spontaneous transmitter release by mechanisms
      downstream of Ca2+ entry. The relative contribution of the above mechanisms to
      the inhibition of elicited release has been debated for a long time. Recent
      evidence at synapses where the relationship between transmitter release and
      presynaptic Ca2+ influx has been well characterized suggests that inhibition of
      presynaptic voltage-dependent Ca2+ channels plays the major role in presynaptic
      inhibition of elicited neurotransmitter release. In addition, modulation of the
      release machinery might contribute to inhibition of elicited release.

PMID- 9141198
TI  - Sprouting in the hippocampus is layer-specific.
AB  - Partial removal of layer-specific afferents of the hippocampus is said to induce
      sprouting of intact fibers from neighboring layers that invade the zone of the
      degenerating axons. However, recent in vivo and in vitro studies using sensitive
      anterograde tracers have failed to demonstrate sprouting across laminar
      boundaries. Sprouting does occur; but, it mainly involves unlesioned fiber
      systems terminating within the layer of fiber degeneration in addition to the
      degenerating afferents. These findings point to rigid laminar cues attracting
      certain fiber systems while repelling others in normal development and after
      partial deafferentation.

PMID- 9141199
TI  - The DnaJ-like cysteine string protein and exocytotic neurotransmitter release.
AB  - The fast, tightly regulated release of neurotransmitters from presynaptic nerve
      terminals is effected by a complex molecular apparatus. The precise roles of the
      various proteins involved remain largely conjectural. Cysteine string proteins
      (CSPs) are novel synaptic vesicle components that have been conserved in
      evolution. They are characterized by an N-terminus 'J'-domain and a central,
      multiply palmitoylated string of cysteine residues. Vertebrate CSPs have been
      implicated in a functional interaction of synaptic vesicles with presynaptic Ca2+
      channels. Genetic 'knockout' of CSPs in Drosophila results in a temperature
      sensitive breakdown of elicited transmitter release. Here we try to integrate
      these observations into speculative functional models on the role of this new
      protein family in synaptic vesicle exocytosis.

PMID- 9141200
TI  - The c-Jun transcription factor--bipotential mediator of neuronal death, survival
      and regeneration.
AB  - Axon interruption elicits a complex neuronal response that leaves neurons poised
      precariously between death and regeneration. The signals underlying this
      dichotomy are not fully understood. The transcription factor c-Jun is one of the
      earliest and most consistent markers for neurons that respond to nerve-fiber
      transection, and its expression can be related to both degeneration and survival
      including target re-innervation. In vitro experiments have demonstrated that
      expression of c-Jun can kill neonatal neurons but, in the adult nervous system, c
      Jun might also be involved in neuroprotection and regeneration. The functional
      characteristics of c-Jun offer a model for the ability of a single molecule to
      serve as pivotal regulator for death or survival, not only in the response of the
      cell body to axonal lesions but also following neurodegenerative disorders. In
      this model, the fate of neurons is determined by a novel transcriptional network
      comprising c-Jun, ATF-2 (activating transcription factor-2) and JNKs (c-Jun N
      terminal kinases).

PMID- 9141201
TI  - New approaches to oral poliovirus vaccine neurovirulence tests: transgenic mice
      susceptible to poliovirus and molecular analysis of poliovirus. A meeting report
      of the WHO Global Programme for Vaccines and Immunization and the WHO Biologicals
      Unit, Geneva, Switzerland, 26-28 September 1996.

PMID- 9141202
TI  - Long-term persistence of anti-HAV antibodies following active immunization with
      hepatitis A vaccine.
AB  - Seventy-one anti-hepatitis A virus (HAV) negative volunteers were immunized
      against hepatitis A. An inactivated hepatitis A vaccine (HAVRIX, SmithKline
      Beecham), derived from tissue cell cultures, at single doses of 720 ELISA units
      was used following a schedule of vaccinations at month 0.1 and 6. The vaccines
      were tested for the presence of HAV antibodies 1 month after each vaccination and
      then after 2, 3, 4 and 5 years. The annual decrease of anti-HAV titres was 25%.
      Five years after vaccination a protective antibody titre, varying between 20 and
      5200 mIU ml-1, could be demonstrated in all 47 retested volunteers with a
      geometric mean titre (GMT) of 442 mIU ml-1. Levels of anti-HAV-antibodies
      following active immunization were significantly higher in female volunteers.
      This could be consistently demonstrated throughout the observation period. Based
      on these data the antibody persistence was calculated over time. GMTs at
      protective levels higher than 20 mIU ml-1 can be expected to persist for at least
      15 years.

PMID- 9141203
TI  - Booster immunization of low- and non-responders after a standard three dose
      hepatitis B vaccine schedule--results of a post-marketing surveillance.
AB  - Seventy-nine low-responders and 83 non-responders after a previous three-dose
      hepatitis B (HB) vaccine course at 0.1, and 6 months were enrolled to receive
      additional 20 micrograms recombinant HB vaccine doses every 2 months until all
      had anti-HBs levels > or = 100 mIU ml-1. After the first booster, 65.4% had anti
      HBs levels > or = 100 mIU ml-1, 17.9% were low-responders (10-99 mIU ml-1), and
      16.7% remained non-responders (< 10 mIU ml-1). All complying non-responders
      developed anti-HBs levels > or = 100 mIU ml-1 after the third booster at the
      latest, whereas all low-responders reached this level after the second booster.
      Although body mass index affected the response to the first hepatitis B booster,
      when full compliance to regular revaccination was ensured, all non- and low
      responders eventually reached sufficient anti-HBs levels.

PMID- 9141204
TI  - Randomized, comparative trial of 20 micrograms vs 40 micrograms Engerix B vaccine
      in hepatitis B vaccine non-responders.
AB  - Fifty-two adults who had previously received 4 x 20 micrograms doses of hepatitis
      B [Engerix-B] vaccine (appropriately administered into the deltoid muscle) and
      who had failed to develop detectable anti-HBs were randomized to receive a fifth
      dose of Engerix-B (either 20 micrograms or 40 micrograms) intramuscularly
      (deltoid). The participants were blinded as to the contents of the syringe. Anti
      HBs was tested (by EIA) 3 months after the injection. Anti-HBs results from 45
      non-responders were evaluable. Seven vaccinees were excluded; four of these on
      the basis of failure to have follow-up blood collected and three who were found
      to be anti-HBc positive (one HBsAg positive). Twelve of 22 (54.5%) of those
      receiving 20 micrograms of HB vaccine developed anti-HBs, whereas 10 of 23
      (43.5%) who received 40 micrograms developed anti-HBs, showing no significant
      difference between the regimens. The mean geometric titres were 93 +/- 50 and 86
      +/- 51 IU l-1, respectively. Vaccinee groups were well matched for age, sex and
      body mass index and the interval between injection and bleeding. Side-effects in
      those receiving the double (40 micrograms) dose were no different from those
      receiving the normal (20 micrograms) adult dose. On the basis of this study, a
      fifth dose of vaccine in non-responsive vaccinees is recommended. No significant
      advantage of 40 micrograms over 20 micrograms of vaccine was observed. Whilst
      smoking and obesity were common in this cohort of non-responders and probably
      contributed to the individuals primary non-responsive state, these factors had no
      unfavourable effect on response to a fifth dose of vaccine.

PMID- 9141205
TI  - DNA inoculation with a plasmid vector carrying the hepatitis E virus structural
      protein gene induces immune response in mice.
AB  - The plasmid construct, pJHEV, containing the full-length open reading frame 2
      (ORF-2) of hepatitis E virus (HEV) gene, expresses the HEV structural protein ORF
      2 in Cos-7 cells under the control of a hCMV promoter. No ORF-2 protein could be
      detected in Cos-7 cells transfected with either vector alone or with a vector
      containing the ORF-2 of HEV in the incorrect orientation. The successful
      construct was further tested in BALB/c (H-2d) mice for the induction of an ORF-2
      specific immune response. Intramuscular (i.m.) immunization of mice pretreated 24
      h earlier with bupivacaine with the naked DNA construct elicited a humoral immune
      response in 80% and 100% of two separate groups of mice, respectively. No anti
      ORF-2 responses were observed in mice immunized with the vector only. Sera from
      mice injected with pJHEV specifically recognized HEV ORF-2 structural protein
      expressed in recombinant baculovirus in an enzyme-linked-immunosorbent assay
      (ELISA) and Western blot. Anti-ORF-2 serum titers peaked at ca 1:5000 in the
      ELISA and 1:1000 in the Western blot. These titers have remained constant for
      over 12 months after the last boost of pJHEV. To our knowledge, this is the first
      report of the use of DNA-based immunization for the generation of an immune
      response to a HEV structural protein.

PMID- 9141206
TI  - Venezuelan equine encephalitis virus vaccines induce mucosal IgA responses and
      protection from airborne infection in BALB/c, but not C3H/HeN mice.
AB  - Immunization with either a live-attenuated (TC-83) or formalin-inactivated (C-84)
      vaccine for Venezuelan equine encephalitis (VEE) virus protected BALB/c mice from
      lethal VEE infection acquired subcutaneously or by aerosol. While vaccinated
      C3H/HeN mice were also protected from parenteral infection, neither vaccine
      protected these mice from an aerosol infection. The apparent vaccine failures in
      C3H/HeN mice could not be attributed to deficiencies in virus-neutralizing
      antibodies in serum, as these responses were typically of equal or higher titer
      than those observed in protected BALB/c mice before challenge. IgG subclass
      analysis offered no facile explanation: profiles of IgG2 alpha dominance were
      observed in C3H/HeN mice given either vaccine and in BALB/c mice given the live
      attenuated vaccine, whereas BALB/c antibody responses shifted toward IgGl
      dominance after immunization with the killed C-84 vaccine. Data from immunized
      congenic mice showed that the H-2 genes from the C3H/He mice were not singularly
      responsible for the inability of these mice to resist aerosol infection with VEE
      virus. VEE virus-specific IgA responses were detected more frequently in
      respiratory and vaginal secretions obtained from the protected BALB/c mice.

PMID- 9141207
TI  - Novel intranasal immunization techniques for antibody induction and protection of
      mice against gastric Helicobacter felis infection.
AB  - Intranasal (i.n.) delivery of antigen can be highly effective for generating
      circulating and secretory antibody responses. Mice were immunized i.n. with two
      antigens, human IgA, and Helicobacter pylori urease in the presence or absence of
      mucosal adjuvant. To restrict antigen delivery to the upper airways, protein
      solutions were administered in a small volume without anesthesia. Repeated daily
      i.n. administration of antigen without adjuvant elicited high levels of specific
      IgG in serum and IgA in serum, saliva, and feces. Once weekly i.n. immunization
      with co-administration of cholera toxin or Escherichia coli heat-labile toxin as
      adjuvant elicited somewhat lower levels of antibody to urease. When challenged
      with Helicobacter felis, only mice immunized with urease in the presence of
      adjuvant were protected against gastric infection.

PMID- 9141208
TI  - Induction of protective antibodies in Saimiri monkeys by immunization with a
      multiple antigen construct (MAC) containing the Plasmodium vivax circumsporozoite
      protein repeat region and a universal T helper epitope of tetanus toxin.
AB  - Previous attempts in inducing protective immunity against Plasmodium vivax in
      human volunteers and nonhuman primates with recombinant circumsporozoite (CS)
      proteins have been unsuccessful, largely due to the failure of generating
      antibodies against the protective B epitope AGDR in the CS protein repeat region.
      We report here an immunization study in Saimiri monkeys with a multiple antigen
      construct (MAC) containing the P. vivax CS protein repeat region and a T helper
      epitope of tetanus toxin formulated in different adjuvants. Monkeys immunized
      three times with MAC in copolymer P1005, copolymer P1005 plus RaLPS, or MF-75 had
      titers of antibodies against CS repeat, sporozoites and the protective B epitope
      AGDR significantly higher than those immunized with MAC in alum or PBS (P <
      0.05). Antibody levels in animals that received P1005 were maintained at high
      level for 7 months after the last immunization. Upon challenge with 10000
      sporozoites 2 weeks after the last immunization, 75% (three of four) of monkeys
      from the alum group, 50% (three of six) of monkeys from the P1005 plus RaLPS
      group, 40% (two of five) of monkeys from the P1005 group, 33% (two of six) of
      monkeys from the MF-75 group, and 17% (one of six) of monkeys from the MAC alone
      group were fully protected. When immunized animals were challenged again with
      30000 sporozoites 22 weeks after the last immunization. 40% (two of five) monkeys
      from the P1005 group were fully protected. The remaining (three) in this group
      developed low parasitemia (< 2000 parasites mm-3 of blood) after significantly
      longer prepatent period (P < 0.05). In addition, 17% (one of six) of monkeys each
      from the P1005 plus RaLPS and MF-75 groups were also fully protected. Protected
      animals had higher levels of prechallenge anti-AGDR antibody titers than
      unprotected (1933 vs 281 for the first challenge, P > 0.05; 21527 vs 196 for the
      rechallenge, P < 0.05). Anti-AGDR antibody titers were positively correlated with
      the prepatent period of infected animals (r = 0.42 for the first challenge, P >
      0.05; r = 0.60 for the rechallenge, P < 0.05) and negatively correlated with the
      peak parasitemia (r = -0.39 for the first challenge, P < 0.05; r = 0.50 for the
      rechallenge, P < 0.05). The results suggested that when combined with the use of
      potent adjuvants and T helper epitopes, MAC subunit vaccines may potentially
      offer protection against malaria infection.

PMID- 9141210
TI  - Effective adjuvants for the induction of antigen-specific delayed-type
      hypersensitivity.
AB  - Vaccines utilizing poorly immunogenic subunit antigens are dependent upon
      adjuvants to drive the appropriate T cell responses. In an effort to determine
      the ability of several adjuvants to promote cell-mediated immunity (CMI), we
      assessed delayed-type hypersensitivity (DTH) in mice inoculated with heat-killed
      Listeria monocytogenes (HKLM) vaccines. The vaccines were formulated as oil-in
      water emulsions containing one or more of the following bacterial-derived
      immunostimulators: MPL immunostimulant, a monophosphoryl lipid A preparation,
      synthetic trehalose dicorynomycolate (TDCM) and Mycobacterium phlei cell wall
      skeleton (CWS). Oil-in-water emulsions containing HKLM without adjuvants did not
      induce DTH responsiveness in mice. The incorporation of TDCM, or MPL plus TDCM
      and/or CWS to the formulation enabled the HKLM vaccine to stimulate CMI
      characterized by DTH responsiveness. Following antigen challenge the resulting
      increases in footpad thickness ranged from 15-20% and were comparable to the DTH
      driven by complete Freund's adjuvant. Adjuvants composed of MPL/TDCM and
      MPL/TDCM/CWS induced responses equivalent to those measured in mice immunized
      with viable L. monocytogenes, and the responses remained at these levels for at
      least 2 months. Furthermore, in vivo depletion of CD4+ T cells, but not CD8+ T
      cells, abrogated the induction and expression of DTH, indicating that the
      response is mediated by CD4+ T cells.

PMID- 9141209
TI  - Highly attenuated modified vaccinia virus Ankara (MVA) as an effective
      recombinant vector: a murine tumor model.
AB  - Modified vaccinia virus Ankara (MVA), a highly attenuated strain of vaccinia
      virus (VV) that is unable to replicate in most mammalian cells, was evaluated as
      an expression vector for a model tumor associated antigen (TAA) and as a
      potential anti-cancer vaccine. We employed an experimental murine model in which
      an adenocarcinoma tumor line, CT26.CL25, was stably transfected with a model TAA,
      beta-galactosidase (beta-gal). Mice injected intramuscularly with a recombinant
      MVA (rMVA) expressing beta-gal (MVA-LZ), were protected from a lethal intravenous
      (i.v.) challenge with CT26.CL25. In addition, splenocytes from mice primed with
      MVA-LZ were therapeutically effective upon adoptive transfer to mice bearing
      pulmonary metastases of the CT26.CL25 tumor established 3 days earlier. Most
      importantly, i.v. inoculation with MVA-LZ resulted in significantly prolonged
      survival of mice bearing three day old pulmonary metastases. This prolonged
      survival compared favorably to mice treated with a replication competent
      recombinant VV expressing beta-gal. These findings indicate that rMVA is an
      efficacious alternative to the more commonly used replication competent VV for
      the development of new recombinant anti-cancer vaccines.

PMID- 9141211
TI  - Hepatitis B vaccine administration: comparison between jet-gun and syringe and
      needle.
AB  - An open randomized controlled clinical trial was conducted to compare the
      reactogenicity of a recombinant hepatitis B vaccine (Engerix-B) when injected
      with the Bioject device (a pneumatically powered drug delivery system using
      disposable syringes) or with conventional syringe and needle, according to a 0.1
      and 6 month vaccination schedule. Ninety-seven healthy young adults were enrolled
      in this study. Participants were asked to record local and general solicited
      symptoms and signs after each vaccination and to report each unsolicited symptom
      and sign that occurred during the study. The use of the jet-gun induced a
      statistically significant higher incidence of local symptoms and signs (solicited
      and unsolicited) than the use of syringe and needle.

PMID- 9141212
TI  - Romurtide, a synthetic muramyl dipeptide derivative, promotes
      megakaryocytopoiesis through stimulation of cytokine production in nonhuman
      primates with myelosuppression.
AB  - The response of megakaryocytes and cytokines to the administration of romurtide,
      a synthetic muramyl dipeptide derivative, was investigated in monkeys with
      myelosuppression by carboplatin-treatment. Romurtide increased the number of
      megakaryocytes and promoted the shift of megakaryocytes towards high ploidy class
      indicative of the promotion of the proliferation and maturation of
      megakaryocytes. The serum levels of interleukin-6, stem cell factor, and
      erythropoietin elevated significantly before the enhanced response of
      megakaryocytes induced by romurtide was observed. Romurtide also enhanced
      production of colony-stimulating factors (CSFs), such as granulocyte-CSF,
      macrophage-CSF, and granulocyte-macrophage CSF by monkey mononuclear cells. The
      stimulating effect of romurtide on the production of those cytokines and CSFs is
      likely to be responsible for the subsequent promotion of the proliferation and
      maturation of marrow megakaryocytes.

PMID- 9141213
TI  - Large-scale production in Pichia pastoris of the recombinant vaccine Gavac
      against cattle tick.
AB  - A gene coding for the Bm86 tick protein was recently cloned, expressed in Pichia
      pastoris and shown to induce an inmunological response in cattle against ticks.
      Moreover, the Gavac vaccine (Heber Biotec S.A., Havana, Cuba), which contains
      this recombinant protein, has proved to control the Boophilus microplus
      populations under field conditions. This paper reviews the development and large
      scale production of this vaccine, the efficacy of the resulting product and the
      strategy followed in designing its production plant. The production plant
      fulfills biosafety requirements and GMP.

PMID- 9141214
TI  - Subgroup specific protection of mice from respiratory syncytial virus infection
      with peptides encompassing the amino acid region 174-187 from the G glycoprotein:
      the role of cysteinyl residues in protection.
AB  - We identified subgroup specific protective epitopes represented by the amino acid
      regions 174-187 and 171-187 of the G glycoproteins from respiratory syncytial
      virus (RSV), subgroups A and B. Mice immunized with coupled synthetic peptides
      corresponding to either the region 174-187 containing a Cys186-->Ser substitution
      or to the native region 171-187 were completely resistant to RSV infection but
      only to the respective virus. The protective activities of the peptides 174-187
      were dependent on the Cys186-->Ser substitution. In addition, a recombinant
      protein representing the region 125-203 of the A subgroup G glycoprotein
      expressed in Escherichia coli was capable without further treatment to completely
      protect animals against RSV subgroup A infection. We show that the combinations
      of cysteinyl residues (positions 173, 176, 182, and 186) retained within either
      synthetic peptides or the recombinant protein G125-203 greatly influenced their
      protective activities. This indicates that the region 171-187 is essential for
      the protection conferred by the G125-203 protein. Furthermore, our results
      strongly suggest that the peptides' and recombinant protein's potencies are a
      function of a loop-like structure which is stabilized by intramolecular disulfide
      linkages between Cys176-Cys182 and Cys173-Cys186. This is further supported by
      the observation that chemical blocking of the sulfidryl groups in synthetic
      peptides completely eliminated their protective activity.

PMID- 9141215
TI  - Influenza-specific immunity induced by recombinant Listeria monocytogenes
      vaccines.
AB  - In this study, we evaluate two Listeria monocytogenes strains that express
      influenza nucleoprotein (NP) sequences for their ability to protect against
      challenge with influenza-virus. The construction of one strain, which expresses
      only the Kd restricted NP epitope (NP 147-155), is described in this study; the
      other strain, which expresses the full NP sequence in the form of a fusion
      protein, has been described previously. The ability of the two strains to present
      the Kd restricted NP epitope in vitro and induce NP-specific CTL in vivo is also
      described. Mice immunized by the intravenous route with either strain cleared a
      subsequent (3 weeks post-immunization) influenza virus infection more rapidly as
      indicated by reduced virus titers in the lungs 5 days after challenge. Efficacy
      of both recombinant L. monocytogenes strains as vaccines in this system was
      equivalent and equal to that of recombinant vaccinia expressing NP.

PMID- 9141216
TI  - Potent immunogenic short linear peptide constructs composed of B cell epitopes
      and Pan DR T helper epitopes (PADRE) for antibody responses in vivo.
AB  - Induction of humoral immune responses against protein antigen requires that two
      independent signals be delivered to B cells. It is currently assumed that simple
      monovalent synthetic peptides would not be effective immunogens for antibody
      responses because they would not be anticipated to effectively generate the
      necessary signals unless conjugated to a complex carrier system. In this study,
      the immunogenicity of short linear peptide constructs comprising Plasmodium vivax
      B cell epitopes (PVB) and non-natural Pan-DR T helper cell epitopes (PADRE) was
      assessed in mice and compared to other types of antigen constructs. The 33
      residue PADRE-PVB linear constructs were highly immunogenic and induced responses
      comparable to those obtained with the multiple antigen peptides (MAP) constructs,
      both in terms of absolute titers and quality of antibody responses. The anti-PVB
      antibody responses were of long duration, composed mostly of IgG and reactive
      with intact sporozoites. The PADRE-PVB constructs were immunogenic when
      formulated in adjuvants such as Alum and Montanide ISA 51 underlining the
      relevance of these findings for vaccine development.

PMID- 9141217
TI  - Clinical immunogenicity and tolerance studies of liquid vaccines delivered by jet
      injector and a new single-use cartridge (Imule): comparison with standard syringe
      injection. Imule Investigators Group.
AB  - A new needleless jet-injector, Mini-Imojet, was developed that administers liquid
      vaccines from a single-use, pre-filled cartridge named Imule, which avoids the
      risk of cross-contamination. We conducted clinical trials in several settings in
      France and West Africa to compare the immunogenicity and tolerance of five
      vaccines (influenza vaccine, Vi capsular polysaccharide typhoid vaccine, tetanus
      toxoid vaccine, diphtheria-tetanus-whole cell pertussis vaccine, and inactivated
      hepatitis A vaccine) administered with the Imule system vs standard syringe
      technique. In each vaccine study, all subjects of either group were tested for
      serum antibody titres to calculate the geometrical mean titres and seroconversion
      rates after complete vaccination. Immediate local-reactions were noted after each
      injection, and local and general reactions were evaluated during a predetermined
      period of follow-up. When delivered by the Imule technique, all the administered
      vaccines were of equivalent or superior immunogenicity, compared to the syringe
      technique. The tolerance to vaccines injected by the Imule system was acceptable
      in all studies. The most frequently observed reactions were mild (e.g. minor
      bleeding, superficial papules, erythema and induration) and could be considered
      to be inherent to the injection technique. The technical and safety advantages of
      the Mini-Imojet/Imule system, compared to sterilizable, standard disposable or
      autodestruct syringes and to classical multi-dose vial jet-injectors, reinforces
      the interest of this new injection technique for collective immunizations.

PMID- 9141219
TI  - E coli O157: lessons of the Scottish outbreak.

PMID- 9141218
TI  - Preparation of diphtheria vaccines using highly purified toxins.

PMID- 9141220
TI  - An outbreak of respiratory disease in horses associated with Mycoplasma felis
      infection.
AB  - Lower respiratory tract disease developed in a group of racehorses in training
      between two and six years of age. Disease was observed in 22 of 25 horses for
      which full records were available. Seroconversion to Mycoplasma felis was
      demonstrated by indirect haemagglutination assay in 19 of 22 paired sera and high
      titres (> or = 64) were found in convalescent sera from the three remaining
      horses. Evidence of respiratory viral infection was confined to seroconversions
      to equine herpesvirus-4 in two of the horses. Tracheal wash samples, taken from
      four horses with visibly increased tracheal mucopus, contained more than 10(4)
      colony forming units/ml M felis and high proportions of neutrophils. This is the
      first description of an outbreak of lower respiratory tract disease in horses in
      training associated with M felis infection.

PMID- 9141221
TI  - Eradication of porcine factor H deficiency in Norway.
AB  - In pigs a hereditary deficiency of the complement-inhibitory protein factor H
      consistently leads to the development of lethal membranoproliferative
      glomerulonephritis type II. This autosomal recessive disease has been a common
      cause of early losses of piglets in the Norwegian Yorkshire breed, but has not
      been reported in the Norwegian Landrace breed. The aim of the present work was to
      identify carriers of factor H deficiency and to eradicate the disease from
      commercial pig populations. Factor H in plasma was measured by an enzyme
      immunoassay. Sixteen known carriers of the disease (parents of factor H-deficient
      offspring) had half the level of factor H (median 110, range 87 to 156 mg/litre)
      recorded in 17 homozygous healthy Yorkshire pigs (median 212, range 183 to 293
      mg/litre) and 20 Landrace pigs (median 227, range 200 to 255 mg/litre). Factor H
      analysis in 397 piglets produced by the mating of known carriers revealed an
      approximately 1:2:1 distribution of individuals with very low, half-normal and
      normal levels of factor H representing homozygous deficient, heterozygous and
      homozygous healthy individuals. Thus, carriers could be identified reliably by
      measuring the plasma concentration of factor H. Most of the population of
      Norwegian Yorkshire breeding pigs (490 pigs) was therefore examined, and a half
      normal factor H level consistent with the carrier state was found in 13.5 per
      cent. These animals were prevented from breeding and since then no losses of
      piglets suspected of being due to factor H deficiency have been reported. No
      carrier was identified among 102 Norwegian Landrace boars, almost excluding the
      existence of factor H deficiency in this breed.

PMID- 9141222
TI  - Field evaluation of a fenbendazole slow release bolus in the control of nematode
      infections in first-season cattle.
AB  - The efficacy of a fenbendazole slow release bolus in controlling nematode
      infections of first-season cattle was evaluated in a field study in northern
      Germany. Two groups, each of 11 male calves, were set-stocked on separate
      pastures from May until October 1989 (157 days). The animals of one group were
      given the bolus at turnout and the animals of the control group were treated with
      fenbendazole (7.5 mg/kg bodyweight) eight weeks after turnout. Clinical
      inspections and measurements of faecal egg and larval counts, herbage
      trichostrongyle larval counts, plasma pepsinogen concentrations and bodyweight
      were made throughout the study. All the animals were slaughtered for worm counts
      and the evaluation of carcase quality two weeks after housing. The pasture grazed
      by the control group showed a marked increase in trichostrongyle larvae from late
      August onwards and, as a result, the control calves had increasing faecal egg
      counts and increased plasma pepsinogen concentrations in the latter part of the
      grazing season, although no clinical signs of parasitic gastroenteritis were
      apparent. The fenbendazole slow release bolus suppressed the trichostrongyle
      infections during the grazing season, and larval counts on the pasture grazed by
      the bolus-treated group remained low throughout the study. Postmortem examination
      showed that the bolus-treated calves harboured significantly (P < 0.01) fewer
      trichostrongyle worms, including inhibited stages, than the controls. Because of
      an inadequate lungworm challenge during the grazing season it was not possible to
      evaluate the efficacy of the fenbendazole slow release bolus in preventing
      parasitic bronchitis. At slaughter, the bolus-treated animals weighed more than
      the controls and tended to have a better carcase quality.

PMID- 9141223
TI  - Case study of bovine dermatitis caused by oat straw infected with Fusarium
      sporotrichioides.
AB  - A dermatitis characterised by discrete, raised, plaque-like and cracked skin
      lesions of variable sizes on the udder, the hind quarters, the lips and muzzle of
      all the cows in a herd was suspected of being caused by the oat straw used in
      bedding, after initial feed analysis and skin culture were negative for toxins
      and dermatophytes. Mycological analysis indicated an extensive infestation of the
      oat straw by Fusarium sporotrichioides, a toxic mould, and an immunochemical
      assay indicated dermatotoxic trichothecenes in the straw (0.22 microgram/g dried
      straw). An ethyl acetate extract of the straw induced a necrotic response on
      shaved rat skin. Ingestion of the toxic bedding straw and inhalation of toxic
      straw dust probably also caused the internal haemorrhage and lung emphysema
      observed in the two cows that died. The regression of the dermatitis and the
      recovery of general herd health after the withdrawal of the oat straw further
      supported the diagnosis.

PMID- 9141224
TI  - Clinical infectious pancreatic necrosis virus infection in farmed halibut in the
      United Kingdom.

PMID- 9141225
TI  - Isolation and identification of adenoviruses from ostriches (Struthio camelus).

PMID- 9141227
TI  - Monitoring suspected adverse reactions.

PMID- 9141226
TI  - Post-thaw in vitro survival of vitrified cloned bovine embryos.

PMID- 9141228
TI  - Foot-and-mouth disease in Taiwan.

PMID- 9141229
TI  - BVD virus antigen in Purkinje fibres in a calf.

PMID- 9141230
TI  - Kitchen hygiene.

PMID- 9141231
TI  - Effects of atenolol as add-on therapy to fosinopril in heart failure.
AB  - Several trials have demonstrated functional benefit with beta-blockers in
      patients with chronic heart failure. The aim of this observational study was to
      investigate if additional beneficial effects can be obtained from beta-blockade
      in a heart failure population that is already receiving high-dose ACE-inhibitor
      therapy. Atenolol is a long-acting cardioselective beta-blocking agent and is
      devoid of additional vasodilatory properties. Twenty-five male patients with
      class II or III heart failure and background therapy of digitalis, furosemide and
      20 mg fosinopril per day were treated with 40 mg fosinopril per day and
      additional 75 mg atenolol per day (beta-blocker group) or with 40 mg fosinopril
      per day alone (control group). At the end of one year, changes in left
      ventricular function, exercise parameters and plasma neurohumoral variables
      reflecting vasoconstriction (noradrenaline, big endothelin) were measured and
      compared in the two treatment groups. Nineteen patients completed the study. Drop
      outs were due to death (4 patients) and non-compliance (2 patients) with no
      significant difference between the groups. There was a beta-blocker related
      improvement in left ventricular ejection fraction (p < 0.05 between groups) and
      an increase in peak oxygen consumption in the control group only (p < 0.05
      between groups). Thus, in a heart failure population receiving high-dose ACE
      inhibitor background therapy beta-blockade with atenolol produced additional
      benefit by reversing left ventricular dysfunction.

PMID- 9141233
TI  - First-pass metabolism and biliary recirculation of droloxifene in the female
      Sprague-Dawley rat.
AB  - 1. Utilizing a validated ultrasensitive hplc assay (lower limit of quantitation
      25 pg/ml), we characterized the disposition profile of droloxifene in the female
      Sprague-Dawley rat following intravenous, oral and intraportal administration. 2.
      The site and extent of first-pass metabolism and the extent of enterohepatic
      recirculation were investigated. 3. Our findings suggest that the intestine is
      neither a metabolic nor an absorptive barrier to the bioavailability of
      droloxifene in the female Sprague-Dawley rat and that first-pass hepatic
      extraction is approximately 70-80% following an oral dose of 1 mg/kg. 4.
      Employment of a modified linked-rat model revealed that droloxifene is subject to
      enterohepatic recirculation (approximately 5%) in the rat.

PMID- 9141232
TI  - Contribution of human CYP3A subfamily members to the 6-hydroxylation of
      chlorzoxazone.
AB  - 1. The capability of human CYPs other than 2E1 to catalyse the formation of 6
      hydroxychlorzoxazone (6OHCHZ) was examined in vitro using human liver microsomes.
      2. 4-Methylpyrazole, diethyldithiocarbamate (DDC), and rabbit anti-human CYP2E1
      antibodies reduced chlorzoxazone 6-hydroxylase activity by 60, 60 and 50%
      respectively. The rate of formation of 6OHCHZ by DDC-treated microsomes was
      reduced further by the 3A inhibitors midazolam, troleandomycin and gestodene and
      increased by alpha-naphtholavone, a 3A4 stimulator. 3. Following preincubation
      with DDC there were significant correlations (p < 0.05) between the residual CHZ
      6-hydroxylase activity and immunoquantified CYP3A levels, and corresponding
      activities (e.g. midazolam 1'-hydroxylation). Rabbit anti-human CYP3A antibodies
      alone and in combination with DDC reduced the formation of 6OHCHZ by 47 and 62",
      respectively. 4. cDNA expressed CYP3A4, 2E1 and 2D6 exhibited comparable CHZ 6
      hydroxylase activity. CHZ modulated 3A4 activity as reflected by midazolam 1'
      hydroxylase and 4-hydroxylase activities. 5. CYP3A may make a significant
      contribution to CHZ 6-hydroxylation and therefore caution should be exercized
      when chlorzoxazone is employed as a specific 2E1 probe in vitro and in vivo.

PMID- 9141234
TI  - Pharmacokinetics of and CYP1A induction by pyridine and acetone in the rat:
      interactions and effects of route of exposure.
AB  - 1. Male Sprague-Dawley rats were exposed to either pyridine, acetone or a
      combination of both compounds by either intraperitoneal administration (100 mg/kg
      pyridine or 400 mg/kg acetone) or whole-body inhalation (200 ppm pyridine or 1000
      ppm acetone). Plasma and tissue levels of both compounds were determined by gas
      chromatography/mass spectrometry. 2. Both chemicals were well distributed in the
      tissues examined following either route of exposure, with concentrations in the
      order kidney > liver > plasma > lung. 3. Plasma half-life of pyridine was 7 h
      following a single 100 mg/kg dose of the compound, and 8 h following the last
      dose of a 3-day, 8 h/day exposure to a 200 ppm inhalation dose of the compound.
      4. Plasma half-life of acetone was 4 h and was independent of the route of
      exposure. 5. The pharmacokinetics of pyridine was not affected by co-exposure to
      acetone. Similarly, the pharmacokinetics of acetone was not affected by co
      exposure to pyridine. 6. Ethoxyresorufin O-deethylase activity in lung and liver
      and methoxyresorufin O-demethylase activities in liver were induced by pyridine
      but not by acetone at the doses examined. Pyridine-induced ethoxyresorufin O
      deethylase activity was higher following inhalation exposure than following i.p.
      administration of pyridine but did not parallel tissue levels of the compound.

PMID- 9141235
TI  - (-)-salbutamol sulphation in the human liver and duodenal mucosa: interindividual
      variability.
AB  - 1. Salbutamol as a beta 2-adrenergic agonist used in the treatment of lung
      obstructive disease and premature labour. It has a bioavailability of 50% and
      sulphation is the main route of its metabolism. (-)-Salbutamol retains most of
      the beta 2-adrenergic activity and, thereby, we describe the interindividual
      variability in the sulphation rate of (-)-salbutamol in 100 specimens of human
      liver and duodenal mucosa. 2. The mean rate (pmol/min/mg of salbutamol sulphation
      was 498 in the duodenum and 141 in the liver with 4-fold variation within +/-2 SD
      units in both tissues. 3. A modelling approach based on the comparison of the
      best fittings obtained using a gaussian and the sum of two gaussian curves
      revealed the presence of two subgroups in the hepatic rate of salbutamol
      sulphation and their means were 69.5 and 105 pmol/min/mg (p < 0.05). In the
      duodenum, the rate of salbutamol sulphation approached normality. 4. The rates of
      salbutamol and 4-nitrophenol sulphation correlated highly (r = 0.853; p < 0.001)
      in the liver whereas in duodenum the rates of salbutamol and dopamine correlated
      highly (r = 0.914; p < 0.001), 4-Nitrophenol and dopamine are the diagnostic
      substrates of phenol- and catechol-sulphotransferases respectively. These
      findings are consistent with the view that the rate of salbutamol sulphation is
      higher in the gut than in liver and it varies considerably in both tissues.

PMID- 9141236
TI  - A hypothetical model for the active site of human cytochrome P4502E1.
AB  - 1. A model for the active site structure of human cytochrome P4502E1 based on the
      coordinates of cytochrome P450BM-3 crystal structure and the sequence analysis
      information on P4502E1 was proposed. 2. The sequence alignment of mammalian P4502
      family and P450BM-3 indicated a 48%, similarity and 25% identity. Secondary
      structural prediction displayed a similar pattern of distribution in the main
      frame of secondary elements, alpha-helices and beta-sheets. The locations of
      secondary elements also mapped well. In addition, the amino acids responsible for
      the conserved secondary structural regions showed the most similarity between the
      two proteins. In contrast, the amino acids responsible for the loop region had
      the least similarity in our alignment. 3. The predicted P4502E1 active site model
      shows that the active site is small and contains mainly hydrophobic residues. The
      substrate binding pocket is located on top of pyrrole rings A and D of the haen;
      in contrast, the access to B and C rings is partially or completely blocked by
      protein side chains. 4. Residues within possible contact of a representative
      substrate, N-nitrosodimethylamine, are He115, Ala299, Thr303, Val364 and possibly
      He469.

PMID- 9141237
TI  - Fungal transformations of antihistamines: metabolism of cyproheptadine
      hydrochloride by Cunninghamella elegans.
AB  - 1. Metabolites formed during incubation of the antihistamine cyproheptadine
      hydrochloride with the zygomycete fungus Cunninghamella elegans in liquid culture
      were determined. The metabolites were isolated by hple and identified by mass
      spectrometric and proton nmr spectroscopic analysis. Two C elegans strains, ATCC
      9245 and ATCC 36112, were screened and both produced essentially identical
      metabolites. 2. Within 72 h cyproheptadine was extensively biotransformed to at
      least eight oxidative phase-I metabolites primarily via aromatic hydroxylation
      metabolic pathways. Cyproheptadine was biotransformed predominantly to 2
      hydroxycyproheptadine. Other metabolites identified were 1- and 3
      hydroxycyproheptadine, cyproheptadine 10,11-epoxide, N-desmethylcyproheptadine, N
      desmethyl-2-hydroxycyproheptadine, cyproheptadine N-oxide, and 2
      hydroxycyproheptadine N-oxide. Although a minor fungal metabolite, cyproheptadine
      10,11-epoxide represents the first stable epoxide isolated from the microbial
      biotransformation of drugs. 3. The enzymatic mechanism for the formation of the
      major fungal metabolite, 2-hydroxycyproheptadine, was investigated. The oxygen
      atom was derived from molecular oxygen as determined from 18O-labelling
      experiments. The formation of 2-hydroxycyproheptadine was inhibited 35, 70 and
      97% by cytochrome P450 inhibitors metyrapone, proadifen and 1-aminobenzotriazole
      respectively. Cytochrome P450 was detected in the microsomal fractions of C.
      elegans. In addition, 2-hydroxylase activity was found in cell-free extracts of
      C. elegans. This activity was inhibited by proadifen and CO, and was inducible by
      naphthalene. These results are consistent with the fungal epoxidation and
      hydroxylation reactions being catalysed by cytochrome P450 monooxygenases. 4. The
      effects of types of media on the biotransformation of cyproheptadine were
      investigated. It appears that the glucose level significantly affects the
      biotransformation rates of cyproheptadine; however it did not change the relative
      ratios between metabolites produced.

PMID- 9141239
TI  - Alveolar-capillary membrane diffusing capacity and its role in the functional
      capacity of chronic heart failure patients.

PMID- 9141238
TI  - Medical and non-medical approaches to renovascular hypertension.

PMID- 9141240
TI  - Opacification of the thoracic aorta after venous injection of sonicated albumin
      microbubbles. Implications for aortic dissection.
AB  - This study was designed to assess the feasibility of thoracic aorta opacification
      after intravenous injection of sonicated albumin microbubbles in patients with
      and without aortic dissection. Twenty-one patients were studied by
      transesophageal echocardiography. In 11 patients without aortic dissection, the
      opacification of the left ventricular outflow tract, aortic root and descending
      aorta was evaluated. Ten patients with aortic dissection were studied to assess
      perfusion of the true and false lumen. The left ventricular outflow tract, aortic
      root and descending aorta were opacified in all patients, with a systolic
      increase in contrast at visual analysis and at videodensitometry. The
      differentiation between false and true lumen was improved and was crucial in 1
      case of type A chronic dissection. The intimal tear was detected in 7/9 cases by
      color Doppler vs 9/9 cases by contrast echocardiography. The noninvasive
      ultrasound opacification of thoracic aorta is feasible and may improve the
      diagnosis of aortic dissection.

PMID- 9141241
TI  - Hibernating myocardium--mechanisms and clinical implications.
AB  - Hibernating myocardium is defined as persistently impaired myocardial and left
      ventricular function at rest resulting from reduced myocardial blood flow. It is
      postulated that despite the reduced coronary blood flow, metabolic activity is
      sufficient to prevent tissue necrosis. Recovery of the hibernating myocardium has
      clearly been shown to occur with the establishment of successful
      revascularization either by coronary bypass surgery or by percutaneous
      transluminal coronary angioplasty. The differentiation of viable, hibernating
      myocardium from non-viable myocardium in patients with coronary artery disease
      and left ventricular dysfunction is a key issue in the current era of myocardial
      revascularization.

PMID- 9141242
TI  - Present views on toxidynamics of soman poisoning.
AB  - This paper summarizes present views on effects of soman (O-pinacolyl
      methylphosphonofluoridate) and on possibilities of treatment of intoxication with
      this highly toxic compound. Simultaneously, it indicates the problems need to be
      solved. On this base only, it will be possible to improve the therapy of soman
      intoxication which is not sufficiently effective at present.

PMID- 9141243
TI  - Acute haemodynamic effects of diltiazem and its distribution in relation to the
      myocardial infarction size.
AB  - The aim of this study was to contribute to an elucidation of some possible
      mechanisms underlying harmful haemodynamic effects of calcium antagonist
      diltiazem in large myocardial infarctions in rats. Acute haemodynamic effects of
      i.v. diltiazem in a single dose of 0.5 mg/kg and the distribution of diltiazem in
      selected tissues was measured four weeks after surgical imposition of myocardial
      infarction in urethane (1.2 g/kg i.p.) anaesthetized rats. Hypotensive effect of
      diltiazem was significantly (r = 0.624) attenuated with an increasing infarction
      size. A significant relationship (r = -0.697) between change in stroke index and
      infarction size was observed. In rats with small infarctions (< 32% of the left
      ventricle circumference) there was an absolute increase, and in rats with large
      infarctions (> 32%) there was an absolute decrease in the stroke index. From the
      results obtained it seems likely that dilatation of ventricles without
      appropriate hypertrophy accompanying large infarctions is one of the main
      determinants of manifestation of negative inotropic potential of diltiazem.

PMID- 9141244
TI  - Video-signal synchronizes registration of visual evoked responses.
AB  - Autodesk Animator software offers the suitable technique for visual stimulation
      in the registration of visual evoked responses (VERs). However, it is not
      possible to generate pulses that are synchronous with the animated sequences on
      any output port of the computer. These pulses are necessary for the
      synchronization of the computer that makes the registration of the VERs. The
      principle of the circuit is presented that is able to provide the synchronization
      of the analyzer with the stimulation computer using Autodesk Animator software.

PMID- 9141245
TI  - Computer controlled multisensor thermocouple apparatus for invasive measurement
      of temperature.
AB  - The computer controlled apparatus for invasive measurement of temperature profile
      of biological systems based on original miniature multithermocouple probe is
      described in this article. The main properties of measuring system were verified
      by using the original testing device.

PMID- 9141246
TI  - Summary of the Czech medical resources in the Internet.
AB  - The article describes the most important features of the computer network
      Internet. Various information services are presented such as E-mail, Listserv,
      Gopher, FTP and World Wide Web. The Internet contribution to medical education,
      research contacts, and information exchange is particularly emphasized. Medical
      information sources from the Czech and Slovak Republics are summarized in
      appendices.

PMID- 9141247
TI  - Epstein-Barr virus infection, Hodgkin's disease, non-Hodgkin's lymphoma, and
      reactive follicular hyperplasia in Japanese children: evaluation of paraffin
      embedded specimens using polymerase chain reaction and immunohistochemistry.
AB  - Epstein-Barr virus (EBV) infections are common in Japanese children, with
      infectious by EBV type 1. The relationships between EBV infection and
      lymphadenopathies in Hodgkin's disease (HD), non-Hodgkin's lymphomas (NHL),
      reactive follicular hyperplasia (RFH), and infectious mononucleosis (IM) in 37
      Japanese children were evaluated. Formalin-fixed, paraffin-embedded lymph node
      specimens that were obtained at surgical resection or biopsy were evaluated for
      the presence of EBV DNA and the latent membrane protein-1 (LMP-1) using
      polymerase chain reaction (PCR) and immunohistochemical staining. The PCR
      detected EBV DNA in nine of 13 (69.2%) patients with RFH, including a case of IM,
      all three (100%) patients with HD, and one of 21 (4.8%) patients with NHL. All
      EBV-positive samples contained EBV type 1. Reed-Sternberg's cells in HD were
      immunohistochemically positive for LMP-1, whereas all cases of RFH and NHL were
      negative for LMP-1. Results suggest that EBV infection may be related to HD.
      Although no proof exists that EBV infection contributes to the transformation of
      cells, thus causing RFH or NHL, the present authors suggest that the EBV-positive
      cases in Japanese children demonstrate a relationship between the clinical and
      histopathological features of the lymphadenopathy and EBV-type 1 infection.

PMID- 9141248
TI  - Infectious mononucleosis as a disease of early childhood in Japan caused by
      primary Epstein-Barr virus infection.
AB  - The present study investigated 54 pediatric patients with acute Epstein-Barr
      virus (EBV)-induced infectious mononucleosis (IM) in Japan. Most of the acute
      cases clustered within the first 5 years of life, and the peak incidence was
      observed at around 4 years of age. These patients were arbitrarily separated into
      three age groups (less than 3 years, 3-5 years, and 6-14 years). Fever,
      pharyngitis, lymphadenopathy and hepatomegaly were detected in more than 80% of
      all cases. Tonsillitis and splenomegaly were present in about 60% of cases. Skin
      manifestations and eyelids edema were less often detected in the older age group
      than in the young age groups. In addition to an increase of total white blood
      cell and lymphocyte counts in the peripheral blood, a significant increase in the
      percentage of CD3+ CD8+ HLA-DR+ T cells was always observed. Epstein-Barr virus
      seropositivity increased soon after birth and reached approximately 70% around 3
      years of age. Close to 100% of the adult controls were EBV seropositive. The
      results suggest that EBV-induced acute IM is a disease of early childhood in
      Japan.

PMID- 9141249
TI  - Nitrogen dioxide production in a nitric oxide inhalation system using the Servo
      Ventilator 900C.
AB  - During nitric oxide (NO) inhalation therapy, toxicity may be produced by the
      reactive metabolite nitrogen dioxide (NO2). The purpose of the present study was
      to determine the NO2 concentration in a NO inhalation system used for respiratory
      failure in children at relatively low concentrations of NO (< 20 ppm). The
      production of NO2 in the NO inhalation system using the Servo Ventilator 900C
      connected to the test lung under each of 30 combinations of NO concentrations (0,
      4, 8, 12, 16, and 19 ppm) and inspired oxygen (O2) concentrations (21, 40, 60,
      80, and 100%). Pressure controlled ventilation was used with a respiratory rate
      of 20 breaths/min. NO and NO2 measurements were obtained on the inspiratory side
      of the Y-piece connected to the test lung. At a given NO level, increases in the
      concentration of inspired O2 resulted in increases in the concentration of NO2
      produced, as did increases in the amount of NO at a given concentration of O2.
      The mean NO concentration at the inspiratory site of the Y-piece did not exceed
      0.05 ppm (the limit of NO2 as an outdoor air pollutant in the United States) when
      the NO concentration did not exceed 8 ppm, regardless of the O2 concentration. NO
      inhalation therapy for children with severe respiratory failure using the Servo
      Ventilator 900C can be performed safely when the concentration of NO does not
      exceed 8 ppm.

PMID- 9141250
TI  - The safety of a nitric oxide inhalation system with high frequency oscillatory
      ventilation.
AB  - Nitric oxide (NO) inhalation and high frequency oscillatory ventilation (HFOV)
      has been indicated in infants with severe respiratory failure. The purpose of the
      present study was to evaluate the safety of an NO inhalation system with HFOV in
      terms of nitrogen dioxide (NO2) production. The NO inhalation system consisted of
      a high frequency oscillatory ventilator, a neonatal circuit and a test lung. The
      NO concentration was changed from 0 to 19 p.p.m. At each level of NO, the oxygen
      (O2) concentration was changed from 21 to 100%. The NO and NO2 concentrations
      were measured with a chemiluminescence analyzer using a molybdenum converter. The
      NO2 concentration was increased when either the O2 or the NO concentration was
      increased. The interposition of the endotracheal tubes increased NO2
      concentrations at 4 p.p.m. NO. The high stroke volume and high mean airway
      pressure produced a significant increase in NO2 production at 4 p.p.m. NO. The
      increase in NO2 production was prevented by placing a one-way valve at the joint
      of the NO gas line to the inspired limb. It was concluded that the NO inhalation
      system with HFOV can be safely used when a one-way valve is placed at the joint
      of the NO gas line to the inspired limb and when inhaled NO is at a relatively
      low concentration.

PMID- 9141251
TI  - Childhood leukemia: epidemiological investigation and effectiveness in treatment
      in Nagasaki over the past 12 years.
AB  - An epidemiological investigation of childhood leukemia was performed in Nagasaki
      Prefecture. The objective of this investigation was to analyze the disease as a
      whole by studying (i) the incidence classified by year, sex, area and disease
      type, (ii) age of onset, (iii) effectiveness of treatment, (iv) prognosis, and
      (v) possible association with the atomic bombing in 1945. The annual incidence
      was 3.0 per 100,000 children under 15 years of age, lower than the national
      average. There was no significant change in the annual incidence for 12 years. No
      increase in incidence was observed in Nagasaki City and its surrounding areas.
      There was no obvious difference in age of onset and incidence by sex from those
      previously reported. Acute lymphocytic leukemia accounted for a large part of
      childhood leukemia. There was no increase in the incidence of acute non
      lymphocytic leukemia, but its familial occurrence and accumulation were observed.
      The rate of first complete remission and the number of long-term survivors
      increased with the improvement of treatment for acute leukemia. The influence of
      the atomic bomb was not clear when the incidence of disease types was compared
      between areas. The comparison of the disease type ratio in patients of the second
      and third generations of atomic bomb victims with that of patients without a
      family history of atomic bomb exposure also did not show an obvious influence of
      the bomb.

PMID- 9141252
TI  - Anthracycline-induced cardiotoxicity in children with malignancies.
AB  - The anthracyclines (ATC) have been used in the treatment of many pediatric
      patients with malignancies. Their use, however, has been limited by a serious and
      potentially irreversible cardiotoxicity. The medical records of pediatric
      patients with malignancies who received ATC at the Department of Pediatrics,
      Kyushu University, from January 1985 to December 1994 were reviewed. Among the
      120 children with malignancies who received ATC, six patients (5%) developed
      congestive heart failure, 33 (28%) had subclinical cardiac dysfunction, whereas
      81 (66%) showed no evidence of cardiac dysfunction. The incidence of ATC
      cardiotoxicity increased at higher cumulative doses. The earliest cardiotoxicity,
      however, was observed in a patient who received 180 mg/m2 unassociated with other
      risk factors, showing the marked individual variations in its development.
      Children younger than 4 years had a higher incidence of cardiotoxicity compared
      with those older than 4 years (P < 0.01) and are therefore more vulnerable to ATC
      cardiotoxicity. Because serial myocardial biopsies and stress testing are not
      practical in younger children, and radionuclide angiogram is rather costly and
      not appropriate for frequent evaluation, non-invasive tests such as
      echocardiography and electrocardiography (ECG) still play the main role for
      serial cardiac monitoring in these age groups. Radionuclide angiogram should be
      added as the confirmatory test modality.

PMID- 9141253
TI  - Carnitine depletion during total parenteral nutrition despite oral L-carnitine
      supplementation.
AB  - Carnitine CAR) plays an important role in the beta-oxidation of fatty acids. Less
      attention. however, has been paid to CAR compared to other nutrients even in
      total parenteral nutrition (TPN). To examine CAR metabolism during TPN and the
      effect of simultaneous oral L-CAR supplementation on CAR levels, the blood CAR
      level was measured in a 3-year-old boy receiving long-term TPN because of short
      bowel syndrome. Both the total and acyl CAR in the serum were evaluated under
      various nutritional conditions including oral supplementation of L-CAR. Low CAR
      concentrations were observed especially when lipid containing TPN regimens were
      in place. Oral L-CAR supplementation was not sufficient to restore the low CAR
      levels in the present index patient even when the dose was increased to 120 mg/kg
      in accordance with the result of the L-CAR absorption test that revealed poor
      intestinal absorption of this nutrient. Moreover, a markedly low CAR level was
      measured during the onset of sepsis in the patient, and the blood CAR was
      depleted when lipid metabolism was activated by lipid loading or sepsis. To date,
      the late effects of CAR depletion on child growth have not been well examined. It
      is recommended that the blood CAR level be maintained at normal levels before any
      prominent manifestations of the deficiency have developed. The intravenous
      administration of CAR appears to be necessary to supply a sufficient amount of
      CAR for patients with severe malabsorption.

PMID- 9141254
TI  - Urinary enzyme changes in newborns with unconjugated hyperbilirubinemia.
AB  - Various changes in renal function caused by unconjugated hyperbilirubinemia in
      newborns have been suggested in previous reports. Disclosing an injury in renal
      tubulus epithelium is feasible by measurement of urinary enzymes. Thus, renal
      function tests and urinary enzymes in 25 terms newborns with unconjugated
      hyperbilirubinemia were evaluated before and after phototherapy. Ten healthy term
      newborns without hyperbilirubinemia formed the control group. Mean values of the
      variables obtained before and after phototherapy in the study group and in the
      controls were, respectively: urine osmolality (osm/kg H2O): 0.147 +/- 0.009,
      0.174 +/- 0.011, and 0.153 +/- 0.018; endogenous creatinine clearance (mL/min per
      1.73 m2): 45.7 +/- 2.15, 46.0 +/- 1.6 and 46.7 +/- 3.9; fractional excretion of
      sodium (%): 1.27 +/- 0.30, 0.79 +/- 0.19 and 1.24 +/- 0.07; tubular phosphorus
      reabsorption (%): 85.8 +/- 3.3, 87.8 +/- 2.8 and 86.6 +/- 1.7; urinary N-acetyl
      beta-D glucosaminidase/creatinine (IU/mg): 0.617 +/- 0.226, 0.574 +/- 0.214 and
      0.619 +/- 0.210; fractional excretion of alkaline phosphatase (%): 0.422 +/-
      0.103, 1.001 +/- 0.374 and 0.596 +/- 0.201; fractional excretion of lactic
      dehydrogenase (LDH; %): 0.102 +/- 0.019, 0.121 +/- 0.023 and 0.119 +/- 0.041;
      fractional excretion of AST (%): 0.433 +/- 0.127, 0.530 +/- 0.113 and 0.502 +/-
      0.074; fractional excretion of alanine aminotransferase (ALT; %) 0.856 +/- 0.413,
      1.619 +/- 1.076 and 1.066 +/- 0.366. No significant difference was found between
      these values before and after phototherapy in the study group, or between the
      values before phototherapy in hyperbilirubinemic neonates and in the control
      group. In conclusion, unconjugated hyperbilirubinemia up to a serum level of 18.4
      mg/dL in term neonates does not seem to result in injury of normal tubulus
      epithelium as shown by urinary enzyme levels.

PMID- 9141255
TI  - Bronchial hyper-responsiveness in atopic dermatitis.
AB  - Most patients with atopic dermatitis (AD) have symptoms of asthma at some point
      in their lives, but some do not have any clinical evidence of asthma. Thirty-two
      patients with AD who had never suffered from bronchial asthma were investigated
      by the methacholine inhalation test for the presence of bronchial hyper
      responsiveness (BHR). Serum immunoglobulin E (IgE) levels, mite specific IgE
      antibody, peripheral eosinophil counts, serum levels of eosinophil cationic
      proteins (ECP), and serum levels of major basic proteins (MBP) were determined
      and a skin test to acetylcholine and adrenaline was performed. The percentage of
      cases who showed BHR (minimum dose; Dmin < 50 units) was 31.3% in AD patients and
      19.0% in 21 healthy controls. In those cases, Dmin of methacholine in AD was
      significantly lower than that in the controls (P < 0.01). Serum MBP levels were
      significantly higher in AD with BHR than in those without it (P < 0.05). These
      results indicate that some AD patients without asthma have BHR, and it may be
      related to serum MBP levels.

PMID- 9141256
TI  - Effect of weight changes on serum transaminase activities in obese children.
AB  - To examine the effect of weight changes on serum transaminase activities,
      glutamic oxaloacetic and pyruvic transaminases (GOT/GPT), a 3-month observation
      of 110 obese outpatients treated by a mild regimen for obesity was carried out.
      Patients were divided into two major groups, group I (n = 73) and group II (n =
      37), with or without persistent elevation of serum GOT/GPT (> 30 IU/L), and
      retrospectively classified into four subgroups according to weight changes: group
      A, weight loss > 5%; group B, weight loss of < 5%; group C, an increase of < 5%;
      group D, an increase > 5%. In group IA, the incidence of cases with normalization
      of serum GOT/GPT was 70% and was significantly greater than those of the other
      three subgroups, respectively (P < 0.01). The incidences of decreased serum
      GOT/GPT activities were observed corresponding to the degree of weight changes
      not only in group I (100-27%) but also in group II (100-33%). These facts
      indicate that a mild regimen for obese outpatients for 3 months, significantly
      improves serum transaminase activities in patients not only with weight reduction
      but also weight gain, and that fatty liver may be present even in obese children
      with normal serum transaminase levels. The normalization of serum GPT activity in
      patients with weight gain suggests the presence of another factor contributing
      hypertransaminasemia in pediatric obese patients.

PMID- 9141257
TI  - Evaluation of sponging and antipyretic medication to reduce body temperature in
      febrile children.
AB  - Two hundred and twenty-four children aged 6 months to 5 years, with rectal
      temperatures greater than or equal to 30 degrees (104 degrees F), were randomly
      treated with sponging alone or with medication including a single oral dose of
      aspirin 15 mg/kg, or paracetamol 15 mg/kg, or ibuprofen 8 mg/kg. Twenty-three
      children were excluded from the final analysis because they did not complete the
      study. Demographic characteristics of the patients were found to be comparable in
      all groups. Rectal temperatures were recorded every 30 min for a 3 h period.
      During the first 30 min of intervention, sponging was found to be more effective
      than all of the three medications. After 60 min, the effects of each medication
      became superior to sponging with tepid water in reducing body temperature. Twenty
      three children were excluded from the final analysis because they did not
      complete the study. Comparing the effect of the three different medications, it
      was seen that the antipyretic efficacy of aspirin and ibuprofen were
      significantly more than paracetamol 3 h after intervention (P < 0.05). For the
      management of fever over 39 degrees C, it is therefore recommended to give
      children an antipyretic drug, preferably ibuprofen, and at the same time to begin
      sponging to provide a rapid and sustained antipyresis

PMID- 9141258
TI  - Ofloxacin versus co-trimoxazole in the treatment of typhoid fever in children.
AB  - Ofloxacin has been successfully used in the treatment of typhoid fever and
      Salmonella infectious of adults for many years. However, it has rarely been tried
      for the typhoid fever of children. In the present study, the therapeutic efficacy
      of ofloxacin in the treatment of typhoid fever in children was compared to that
      of co-trimoxazole. Out of 41 patients with bacteriologically documented typhoid
      fever, those with co-trimoxazole-resistant strains received 20 mg/kg ofloxacin
      twice daily for 10 days, and those with co-trimoxazole-susceptible bacteria were
      given 60 mg/kg co-trimoxazole twice daily for 10 days. Both groups were compared
      according to the clinical variables (apyrexia, resolution of gastrointestinal,
      central nervous system reactions and articular symptoms) and the time when
      cultures became negative. All patients in both groups were cured without relapse.
      Apyrexia, resolution of gastrointestinal, central nervous system reactions and
      articular symptoms were obtained in a significantly shorter time with ofloxacin
      than with co-trimoxazole (P < 0.05). The interval between onset of therapy and
      the time when cultures became negative was significantly shorter in the ofloxacin
      group than in the co-trimoxazole group (P = 0.005). Ofloxacin seems to be a good
      alternative in the treatment of typhoid fever caused by co-trimoxazole resistant
      salmonellae in children aged less than 16 years. It is well tolerated by the
      patients and it causes no side effects with short-term usage.

PMID- 9141260
TI  - Agranulocytosis and thrombocytopenic purpura following measles infection in a
      living-related orthotopic liver transplantation recipient.
AB  - Agranulocytosis and thrombocytopenic purpura occurred simultaneously following
      measles infection in a 2-year-old girl who had received a living-related
      orthotopic liver transplantation. Neutrophil and platelet counts rose to more
      than 0.5 x 10(3)/mm and 30 x 10(3)/mm3, respectively, 8 weeks after the onset of
      neutropenia and thrombocytopenia, and within 2 weeks from the start of
      subcutaneous injection of granulocyte colony-stimulating factor. Simultaneous
      occurrence of measles infection, neutropenia and thrombocytopenia has not been
      described before in the literature. An autoimmune mechanism was suspected because
      serum levels of platelet-associated immunoglobulin G (IgG) and anti-neutrophil
      antibody were evaluated during the acute phase.

PMID- 9141259
TI  - Atypical Epstein-Barr virus infection during and after intermittent FK506
      therapy.
AB  - Atypical Epstein-Barr virus (EBV) infection developed in a patient under
      intermittent administration of FK506 (one dose in 10 days) after living-related
      liver transplantation. The clinical course was similar to severe chronic active
      EBV infection syndrome (SCAEBV), which is characterized by extremely high titers
      of antibody to EBV antigens. The clinical symptoms improved without graft
      rejection even after the cessation of FK506; however, the titers of antibody to
      EBV antigens remained at high levels. It was considered that: (i) even
      intermittent use of FK506 could influence the immune response, which then induced
      atypical EBV infection similar to SCAEBV; and (ii) the impaired immune response,
      especially to EBV antigens, remained after complete cessation of FK506.

PMID- 9141261
TI  - Pyruvate dehydrogenase complex deficiency with multiple minor anomalies.
AB  - Pyruvate dehydrogenase complex (PDHC) deficiency is known to cause congenital
      lactic acidosis. The case of a 9-month-old female infant with PDHC deficiency
      caused by a mutation in exon 11 of the pyruvate dehydrogenase (PDH) E1 alpha gene
      is described. Her facial features were as follows: frontal bossing, upslanting
      palpebral fissures, a short upturned nose, a long philtrum and low set ears.
      These anomalies are characteristic not only of a malformation syndrome or
      chromosomal aberration, but also of PDHC deficiency. Because PDHC deficiency
      requires early treatment, metabolic disorders should be kept in mind in a patient
      with dysmorphic features. Further, she had multiple minor anomalies including
      bilateral inguinal herniae, an umbilical hernia and small hands and feet, which
      have not been described in previous reports.

PMID- 9141262
TI  - Double-outlet right ventricle with intact ventricular septum.
AB  - An infant with double-outlet right ventricle (DORV) with intact ventricular
      septum (VS) is described. Hypoplastic left ventricle and mitral valve atresia
      were also associated. To the authors' knowledge, this appears to be the first
      case in which this rare form has been demonstrated with magnetic resonance
      imaging (MRI). The patient required balloon atrial septostomy (BAS) three times
      until 4 months of age because of progressive cyanosis. In such a form of DORV,
      surgical atrial septectomy should be performed instead of repeating BAS because
      the tendency to functional closure of the restrictive secundum arterial septal
      defect caused by incompetent foramen ovale seems to be prominent.

PMID- 9141264
TI  - Introduction to the present status and clinical statistics of collagen diseases
      in the young in Japan.

PMID- 9141263
TI  - Acute fulminant ulcerative colitis with toxic megacolon.
AB  - An 11-year-old boy with acute fulminant ulcerative colitis (UC) is presented. He
      had systemic deterioration with frequent diarrhea and lethargy. Acute fulminant
      UC associated with toxic megacolon was diagnosed by rectal endoscopy and biopsied
      specimen. He was treated with intensive intravenous administration of
      prednisolone and total parenteral nutrition. He recovered completely without any
      surgical intervention.

PMID- 9141265
TI  - A nationwide surveillance study of rheumatic diseases among Japanese children.
AB  - To estimate the number of children with rheumatic diseases, a questionnaire was
      distributed to the pediatrics department of 1,290 hospitals in Japan in June
      1994. From this survey, 1,606 cases with juvenile rheumatoid arthritis (JRA), 906
      cases with systemic lupus erythematosus (SLE), 320 cases with
      dermatomyositis/polymyositis (DM/PM), 28 cases with scleroderma (PSS), 70 cases
      with Sjogren's syndrome (Sjs), 93 cases with mixed connective tissue disease
      (MCTD), 25 cases with aortitis syndrome, 20 cases with polyarteritis (PN) and 51
      cases with Behcet disease were reported. The crude annual incidence rates per
      100,000 among the childhood population were estimated as JRA, 0.83; SLE, 0.47;
      DM/PM, 0.16; PSS, 0.01; Sjs, 0.04; MCTD, 0.05; aortitis syndrome, 0.01; PN, 0.01;
      and Behcet disease, 0.03. The present study reveals that there are more children
      with rheumatic diseases than are estimated from the reported cases in the
      literature and the number of children who are receiving Assistance Medical Costs
      Insurance covered by the Japanese government.

PMID- 9141266
TI  - Clinical analysis of 570 cases with juvenile rheumatoid arthritis: results of a
      nationwide retrospective survey in Japan.
AB  - The purpose of the present study was to investigate the incidence of juvenile
      rheumatoid arthritis (JRA) among Japanese children and to evaluate the clinical
      features of this disease. A questionnaire was sent to the department of
      pediatrics of 1290 hospitals in Japan, in 1994, asking for the number of
      rheumatic patients during the past 10 years. Subsequently, a second questionnaire
      was sent asking for the type of onset, clinical features, treatment, and other
      details. The results of 570 cases were obtained. Of these, 310 cases (54%) were
      the systemic onset type, 140 cases were the polyarticular onset type (25%), and
      120 cases (21%) were the pauciarticular onset type. Hence, in the present series
      of children, the proportion of the pauciarticular type was less than the other
      two types of JRA. In the laboratory findings of the systemic onset type,
      hyperferritinemia and thrombocytosis were noted, in addition to leukocytosis,
      positive C- reactive protein (CRP) and accentuated erythrocyte sedimentation rate
      (ESR). The rheumatoid factor was positive in 50% of patients with the
      polyarticular onset type. Chronic uveitis was recognized in 13 cases (10.8%) of
      the pauciarticular onset type. In four girls, uveitis started before the onset of
      arthritis. Non-steroidal anti-inflammatory drugs were used in almost one-third of
      cases, and methotrexate (MTX) was used in 12.8% of cases. The quality of life of
      children with JRA was disturbed in almost 20% of cases. Therefore, for the early
      and definitive diagnosis of the systemic type of JRA, diagnostic procedures
      including thrombocyte counts and serum ferritin level, should be performed. In
      order to obtain good results and to avoid side effects, a protocol for the use of
      disease modifying anti-rheumatic drugs and immunosuppressants, especially for the
      use of MTX, must be established.

PMID- 9141267
TI  - Clinical features of Japanese children and adolescents with systemic lupus
      erythematosus: results of 1980-1994 survey.
AB  - Marked advances have been made in the past decade in the management of adults
      with systemic lupus erythematosus (SLE). Therefore, a nationwide retrospective
      survey was conducted between 1980 and 1994 to investigate the clinical
      manifestations of SLE in Japanese children and adolescents. Questionnaires were
      sent to 340 hospitals. Of 405 patients reported by 176 hospitals, 373 patients,
      diagnosed by the criteria established by the Pediatric Study Group of the
      Japanese Ministry of Health and Welfare in 1985, were enrolled in the study.
      Forty-nine of the 354 patients (13.8%) had relatives with a connective tissue
      disease within the third degree of consanguinity. The frequent manifestations in
      373 patients were the presence of antinuclear antibody (98.9%), immunologic
      disorders (93.0%), hypocomplementemia (87.1%), malar rash (79.6%) and fever
      (74.0%). Lupus nephritis was present in 148 of the 309 patients (47.9%) at their
      first visit to a clinic, and 261 of the 373 patients (70.0%) developed renal
      involvement during the observation period. Of 370 patients, 92 patients (24.9%)
      exhibited central nervous system lupus. Of 368 patients, 192 patients (52.2%)
      were treated by methylprednisolone pulse therapy and 148 patients (40.2%)
      received immunosuppressants in combination with steroid therapy at some stage
      during the observation period, Survival rate at 5 years from onset was 95.9%.
      Management of infection, coagulopathies, and central nervous system involvement
      is essential to improve the prognosis of SLE in Japanese children and
      adolescents.

PMID- 9141268
TI  - Characteristics of juvenile dermatomyositis in Japan.
AB  - Questionnaires were sent to 1290 hospitals in Japan asking for data on patients
      with juvenile dermatomyositis (JDM) diagnosed between June 1984 and May 1994. Of
      the 204 patients identified by these questionnaires, 102 met the criteria for
      JDM. JDM is categorized into three subtypes: Banker-type JDM, Brunsting-type and
      fulminant-type; patients with the latter exhibit markedly elevated serum levels
      of creatinine phosphokinase (> 10,000 U/mL) and appear to be at risk of renal
      failure. Cutaneous manifestations were present in 98% of patients and preceded
      the appearance of other symptoms. This tendency is one of the reasons for the
      difficulty in some cases in diagnosing the onset of JDM. Better criteria for
      early treatment of JDM are needed. The results of the present study suggest that
      itching and calcinosis are factors that indicate a poor prognosis in patients
      with JDM. Muscle enzyme levels do not always reflect disease activity, suggesting
      that methods other than measurement of muscle enzymes, such as measurement of the
      levels of neoprerin and von Willebrand factor antigen, as well as magnetic
      resonance imaging should be used to be evaluate disease severity. Patients with
      Brunsting-type JDM who exhibit dysphagia and antinuclear antibody positivity and
      patients with Banker-type JDM should be treated aggressively. Pulse therapy
      should be selected as the initial therapy in patients with fulminant-type JDM.

PMID- 9141270
TI  - The clinical features of Sjogren's syndrome in Japanese children.
AB  - Sjogren's syndrome (SS) is thought to be uncommon in children. An epidemiological
      study to describe the clinical features distinguishing SS in Japanese children
      was performed by sending questionnaires to hospitals. A total of 61 cases of SS
      were reported from 1290 hospitals. The diagnosis of SS was based on
      histopathological changes and/or sialographic changes in the salivary glands.
      Forty-two cases had primary SS and 19 were secondary SS with other autoimmune
      disorders. Fourteen cases (65%) of secondary SS were associated with systemic
      lupus erythematosus. In primary SS, the initial symptoms were systemic
      manifestations (fever, exanthema, arthralgia, etc) except for sicca symptoms. In
      laboratory studies, antinuclear antibodies, elevated serum IgG, rheumatoid
      factor, anti-Ro/SS-B antibodies were frequently observed.

PMID- 9141269
TI  - Systemic sclerosis in children: a national retrospective survey in Japan.
AB  - A retrospective questionnaire survey of pediatric departments, for childhood
      collagen disease from 1985 to 1994 was used to clarify the clinical features of
      scleroderma in Japan. In the primary survey, 0.9% of the children with a
      rheumatic condition and scleroderma. Answers to this questionnaire were received
      on 18 (localized 9; systemic 9) patients from 15 institutions. In order to
      examine systemic sclerosis (SSc), seven cases of SSc in Japanese articles during
      the same period as the questionnaire were added to these answers and compared to
      the Japanese epidemic study investigated by Fukuyama in 1974. There were 16
      children, seven boys and nine girls, with SSc during the 10-year period in Japan.
      The mean age of onset of symptoms was 8.0 +/- 2.8 years and the age at diagnosis
      10.1 +/- 3.0 years. Eighty percent of children had Raynaud's phenomenon at the
      onset of SSc, and skin and musculoskeletal involvement was highly recognized
      during the course of the disease. Atrophy of the frenulum linguae and lung
      fibrosis were commonly seen in SSc. In serological studies, 80% of children have
      antinuclear antibodies and approximately 50% of patients have anti-Scl-70
      (topoisomelase I) antibodies at the onset and during the course of childhood SSc.
      The prognosis is poor, as remission occurred in only one child. The clinical
      symptoms and examination of serological autoimmune antibodies were supportive of
      an early diagnosis of SSc. When compared to the previous national survey of
      children with SSc, the present results showed that the male-to-female ratio was
      reduced, the age at onset was low, the positive incidence of serological
      autoimmune antibodies elevated, and the usage of vasodilators and nonsteroid anti
      inflammatory drugs (NSAID) increased, with corticosteroids decreased. But, the
      positive percentage of clinical symptoms were not changed in both studies. For a
      complete retrospective nationwide epidemic survey carried out on children with
      scleroderma, especially SSc, it is important to include dermatology departments.

PMID- 9141271
TI  - Mixed connective tissue disease in childhood: a nationwide retrospective study in
      Japan.
AB  - Sixty-six children with mixed connective tissue disease (MCTD) were analyzed by a
      nationwide prospective study. The diagnostic significance of Raynaud's phenomenon
      and positive anti-RNP antibody was confirmed, and additional symptoms including
      swelling of fingers, facial erythema, and polyarthralgia, and laboratory findings
      such as positive rheumatoid factor, hypergammaglobulinemia, and increased levels
      of myogenic enzymes, were variably positive. These clinical and laboratory
      characteristics of MCTD were critically different from those of systemic lupus
      erythematosus, indicating that MCTD is an independent entity of disease.

PMID- 9141272
TI  - Clinical observation of 14 cases of childhood polyarteritis nodosa in Japan.
AB  - An epidemiological survey of childhood polyarteritis nodosa was conducted at 1290
      hospitals followed by a secondary survey of hospitals that had therapeutic
      experience with the disease. Fourteen cases obtained from these surveys were
      studied clinically. The male-female ratio was 4:3. The mean age at onset was 10.6
      years. To established the diagnosis, skin biopsy was performed in 43%, retrograde
      aortography in 21%, and kidney biopsy in 14% of cases. Non-specific symptoms such
      as fever (86%), skin eruption (50%), arthritis (50%), myalgia (50%), abdominal
      pain (43%) and hypertension (36%) were often noted as clinical findings at the
      initial visit. Throughout the clinical course, symptoms considered to be caused
      by local angiopathy, including interrupted blood circulation, were frequently
      noted. On blood tests, no specific findings other than acute inflammatory
      reaction were observed. Steroid preparations were used for treatment in all cases
      but one, and about half of them are presently free from steroids.
      Immunosuppressants were administered in 10 cases. As for prognosis, all patients
      are alive, but untoward sequelae were noted in 36% of cases. The results of the
      present survey reinforced the difficulty of establishing a final differential
      diagnosis because specific findings were scarce for this disease, as stated in
      previous reports. Establishing a method for early diagnosis by gathering and
      analyzing more data in detail will be necessary in the future.

PMID- 9141273
TI  - Aortitis syndrome in children: clinical observation of 35 cases in Japan.
AB  - The results of clinical observation of 35 patients with aortitis syndrome (AS) in
      childhood, obtained by a nationwide survey in Japan, are reported. The male to
      female ratio was 1:2.5, the estimated age of onset averaged 10.2 years, and the
      duration from the estimated age of onset to the diagnosis averaged 15 months. In
      HLA examination A24, Bw52, Cw7 and DR2 were relatively common. Arterial lesions
      tended to extensively involve the aortic arch and its branches. Fever was the
      most frequently noted clinical symptom, followed by abdomen, joint and muscle
      pain. The physical findings in order of frequency were impaired circulation of
      the upper extremities, cardiac and vascular murmurs, hypertension, impaired
      cerebral circulation, visual disorder and impaired circulation of the pulmonary
      artery. The murmurs were found not only over the chest wall but also over the
      cervical area and abdomen. Pulselessness of the upper extremities occurred in 66%
      of patients. Percutaneous retrograde aortography and/or intravenous digital
      subtraction angiography to make the final diagnosis was employed except for three
      cases. There were not any specific abnormal signs in laboratory data. Steroid
      hormones were administered in 34 cases, and immunosuppressive agents in 8 cases.
      Five cases had percutaneous transluminal angioplasty to the right renal artery as
      an interventional treatment. The high frequency of abdominal pain is considered
      to be one of the characteristics of AS in childhood. The high frequency of
      pulselessness of the upper extremities and cardiac and vascular murmurs in this
      report is considered significant for the diagnosis of AS in childhood.

PMID- 9141274
TI  - Behcet disease in children: a nationwide retrospective survey in Japan.
AB  - The purpose of the present study was to evaluate the incidence of Behcet disease
      among Japanese children and to compare their clinical features with adult
      patients. A first questionnaire was sent to the department of pediatrics of 1290
      hospitals in Japan. Fifty-one cases of Behcet disease among children under 16
      years of age were reported. From a second survey, 31 cases satisfied the criteria
      of the Behcet's Syndrome Research Committee of Japan. Of 31 patients (14 boys and
      17 girls), three cases were the complete type, 24 cases were the incomplete type,
      and four cases were the possible type. As to the specific type of the disease, 10
      cases were of the entero-Behcet type, two were a combination of the entero
      vasculo-Behcet type, and four were the neuro-Behcet type. In the first 6 months
      after onset, oral ulcers were observed in 77% of cases, genital ulcers in 45%,
      uveitis in 10%, and skin lesions were observed in 39% of cases. During the course
      of the disease, the frequency of oral ulcers was 100%, genital ulcers, 58%;
      ocular complications, 29%; and skin lesions, 55%. Gastrointestinal signs and
      symptoms were more frequent in childhood Behcet disease than in adults, while
      ocular complications were less frequent. The diagnosis of Behcet disease in
      children is difficult because of the long interval before the onset of enough
      manifestations to satisfy the diagnostic criteria. Specific diagnostic criteria
      are necessary, based on a discussion of the many childhood cases of Behcet
      disease.

PMID- 9141275
TI  - Circulating soluble L-selectin levels in Kawasaki disease with coronary artery
      lesions.

PMID- 9141276
TI  - Development of coronary artery lesions in Kawasaki disease patients in relation
      to plasma interferon-gamma and interleukin-4 [corrected] levels in the acute
      phase.

PMID- 9141277
TI  - Body composition of mice of different body condition score and sex.
AB  - After a critical review of recent research on the whole body chemical composition
      of laboratory animals, especially that of the mouse, the authors present data on
      the body composition of a mouse line of different body condition score, varying
      from normal to double-muscled ("culard", "compact") type. One hundred male and
      100 female mice of different compact categories were measured in vivo, using
      total body electrical conductivity (TOBEC method), then by direct chemical
      analysis performed on day 77 of life. In male mice, body weight and protein
      content were found to increase while fat content decreased parallel to the
      increase in phenotypic condition score. Female mice showed a rather constant fat,
      protein and ash content in the dry matter of the body. The precision and validity
      of TOBEC data under 40 grams of body weight proved to be insufficient.

PMID- 9141278
TI  - Evaluation of the digestibility of nutrients in pigs by ileal cannulation
      technique.
AB  - A simple T-cannula was surgically inserted into the ileum of growing female Large
      White x Dutch Landrace swine. Chymus samples collected with the help of the
      cannula were analysed to determine the apparent digestibility of different
      dietary nutrients such as dry matter, crude protein and starch, as well as of
      some essential amino acids. The following three experiments were conducted: (I)
      of the cereals, the "Tewo" triticale variety fed alone and in 1:1 concentrate
      mixtures with wheat or maize was studied; (II) waxy maize hybrids and maize
      hybrids of normal endosperm were compared without treatment and after treatment
      by the Bocchi technology; (III) untreated and extruded maize supplemented either
      with extracted soybean or with extracted sunflower was also tested. The ileal
      digestibility of protein, amino acids and starch was determined and compared with
      values obtained by conventional (faecal) analysis. When feeding triticale alone
      or in combination with wheat or maize, the ileal digestibility of crude protein
      and amino acids increased as a result of feeding the cereal combinations (e.g.
      crude protein 72-79%, lysine 75-79%, threonine 63-78%, methionine 74-86%).
      Comparison of the two maize hybrids revealed that, with the exception of
      methionine, lysine and tyrosine, the amino acids of the waxy hybrid had higher
      ileal digestibility. Treatment of the normal hybrid by the Bocchi technology
      caused a significant improvement in the ileal digestibility of cystine,
      isoleucine, lysine, valine, and dry matter. This treatment also improved the
      faecal digestibility of all test nutrients but methionine. Bocchi treatment of
      the waxy hybrid significantly improved the ileal digestibility of isoleucine,
      leucine, methionine, tyrosine and valine, and the faecal digestibility of
      cystine, dry matter, and crude protein. No major variety- or treatment-related
      differences were found in the digestibility of starch. As a result of extrusion,
      the digestibility of nutrients of the soybean + maize mixture increased from
      61.6% to 70.3% (crude protein), from 41.1% to 59.4% (threonine), from 60.1 to
      72.0% (methionine), and from 70.7% to 82.7% (lysine). The same treatment of the
      sunflower + maize mixture increased the digestibility of crude protein from 80.6%
      to 84.5%, that of threonine from 78.1% to 80.6%, that of methionine from 79.7% to
      84.3%, while that of lysine from 61.4% to 72.3%. The ileal digestibility of
      starch was 97-98% for both mixtures. As a result of extrusion, most of the faecal
      digestibility values showed a significant improvement for both the soybean- and
      the sunflower-containing mixtures. The favourable effect exerted by extrusion on
      the digestibility of nutrients is markedly influenced by the feed components.

PMID- 9141279
TI  - Comparison of some blood parameters of captured and farmed red deer (Cervus
      elaphus) hinds.
AB  - In studies on the adaptation of red deer (Cervus elaphus) to farm conditions,
      some blood parameters of 3- to 9-year-old captured and farmed hinds were
      compared. The test variable included blood plasma creatine kinase (CK), alanine
      aminotransferase (ALT), and lactate dehydrogenase (LDH) activities, the
      concentrations of glucose, urea, total protein (TP), serum cortisol, haemoglobin
      (Hb), and the blastogenic transformation of lymphocytes upon stimulation by the
      nonspecific mitogens Phaseolus vulgaris (PHA) and Concanavalin A (ConA) in the
      lymphocyte stimulation test (LST). The effects exerted by probiotic preparation
      (Ascogen) on the same parameters were studied in farmed deer. In hinds that had
      been kept under farm conditions for 10 months, CK activity was lower (P < 0.05)
      and blood urea concentration higher (P < 0.001) than at the time of capture,
      while their blood glucose concentration exceeded (P < 0.01) that of farmed hinds.
      Hinds treated with Ascogen had lower ALT activity (P < 0.001) and showed a higher
      increase in PHA-induced blastogenic transformation of lymphocytes than the
      control hinds.

PMID- 9141280
TI  - Effect of lipid peroxide loading on lipid peroxidation and on the glutathione and
      cytochrome systems in rabbits.
AB  - New Zealand White rabbits (6 males and 6 females) were fed a diet of high lipid
      peroxide content (peroxide value: 249.05 meq/kg fat) for 21 days. Twelve rabbits
      served as controls (peroxide value: 40.3 meq/kg fat). The lipid peroxide loading
      did not cause clinical signs. The rate of lipid peroxidation, as measured on the
      basis of thiobarbituric acid reactive substances (TBARS), was significantly (P <
      0.05) higher in all of the investigated tissues, in the following order: liver >
      red blood cells (RBC) > blood plasma. Reduced and oxidised glutathione content
      was higher in the blood plasma (P < 0.01) and liver (P < 0.001) of rabbits
      exposed to the peroxide load. Lipid peroxide loading decreased the activity of
      glutathione peroxidase in the blood plasma, RBC haemolysate and liver and that of
      glutathione reductase in the liver. The amount of cytochrome P450 (both CO- and
      metyrapone-reduced) and the activity of cytochrome c (P450) oxidoreductase in the
      microsomal fraction of the liver homogenate were also lower in the group exposed
      to lipid peroxide load. Subchronic alimentary lipid peroxide loading in the
      presence of sufficiently high levels of antioxidants in the complete feed was
      found to increase the rate of lipid peroxidation and markedly lower the
      activities of both the glutathione and xenobiotic transforming enzyme systems
      without causing any clinical signs of toxicity.

PMID- 9141281
TI  - Suspected adverse drug reactions in the Hungarian veterinary practice between
      1982 and 1992.
AB  - The most characteristic adverse drug reactions observed after the use of home
      manufactured or imported veterinary medicinal products in Hungary between 1982
      and 1992 included toxicosis, severe local reaction, lack of efficacy, and
      presence of residues in the edible tissues of food animals. The causes of adverse
      drug reactions comprised manufacturing defects, lack of chemical or
      microbiological stability, misuse or extra label use, and neglecting the warnings
      in the directions for use. Collection and analysis of data relating to adverse
      drug reactions are indispensable for the prevention of similar cases. The
      authorities can facilitate data collection by supplying veterinary practitioners
      with the necessary report forms.

PMID- 9141282
TI  - Rapid freezing of mouse embryos in ethylene glycol at different preimplantation
      stages.
AB  - The objectives of this study were to examine the effects of a rapid freezing
      protocol on the survival and in vitro development of mouse embryos cryopreserved
      in ethylene glycol (EG) at different preimplantation stages, and secondly, to
      investigate the effect of exposure to 3.0 M EG with 0.25 M sucrose on the
      survival and in vitro development of mouse embryos without freezing at different
      developmental stages. To perform the rapid freezing procedure, embryos were
      equilibrated in Dulbecco's phosphate buffered saline (DPBS) containing 3.0 M EG
      and 0.25 M sucrose (freeze medium) for 20 min and loaded into 250 microliters
      straws in a single column of freeze medium. The straws were held in liquid
      nitrogen (LN2) vapour for 2 min and immersed into LN2. Embryos were thawed in a
      37 degrees C water bath for 20 sec and transferred to DPBS supplemented with 0.5
      M sucrose (rehydration medium) for 10 min and cultured for 24 to 96 h in HTF
      (Human Tubal Fluid) plus 4 mg/ml BSA (Bovine Serum Albumin). Significant
      differences were found in the survival and development of mouse embryos at
      different developmental stages rapid frozen in EG and sucrose: two cell 43/84
      (51%), 4-8 cell 44/94 (47%), morula and early blastocyst 56/70 (80%), expanding
      and expanded blastocysts 10/59 (17% (p < 0.05). These data indicate that the
      developmental stage in which mouse embryos are subjected to this quick freeze
      protocol affects survival and development in vitro and the majority (80%) of
      morula and early blastocyst stage embryos survive the procedure. No significant
      differences were observed in the in vitro developmental capacity of embryos at
      different developmental stages after treatment with high concentrations (3.0 M)
      of EG solution without freezing. Further investigations are underway to better
      understand the reasons for different survival rates of embryos frozen at
      different developmental stages using the present procedure.

PMID- 9141283
TI  - A comparison of rectal palpation and ultrasonography for the evaluation of
      superovulatory response in beef heifers.
AB  - The superovulatory response was followed up in 14 beef heifers by rectal
      palpation and by ultrasonographic examinations of the 28 ovaries, on day 7 after
      superovulation induced with PMSG (ovulation = day 0). Using a B-mode ultrasound
      instrument (Aloka Echo Camera SSD-210-DX II) equipped with a 5 MHz linear
      transrectal transducer, ultrasonography was found to be more reliable than rectal
      palpation. A significantly higher number of follicles (P < or = 0.049) was
      identified by ultrasound scanning than by rectal palpation of the ovaries:
      follicles were more easily differentiated from cysts using ultrasonography, since
      each fluid-filled vesicle was accurately measured on the screen and presented on
      the echogram.

PMID- 9141284
TI  - Lessons from twins: of nature, nurture, and consciousness.
AB  - Once accorded a high place in the world's mythologies, twins may be poised to
      reappear with new power in the images are archetypal patterns that shape the
      modern mind. On a concrete level, they are influencing how we define ourselves.
      As a result of intrauterine ultrasound studies, we are finding that more of us
      are twins than we ever imagined: a phenomenon dubbed "the twin without." We are
      also learning about within": our complementary "solar" and "lunar" traits of
      which the ancient Twin myths speak, whose integration is one of life's great
      tasks. Some of the most compelling messages of twins are appearing in an
      unexpected area: modern science. One of the great discoveries of 20th-century
      physics is the principle of complementarity: the idea that a subatomic particle
      can possess dual or twin aspects; that under certain experimental conditions it
      can manifest as a particle, and under others a wave. This is an expression of
      what could be called the "Twinship Principle" in modern science. The gene
      environment relationship, which we have examined, is another. We might also add
      the predator-prey relationship in ecology; the alternation of day and night and
      the seasons; the sleep-wake cycle; perhaps even the one-and-zero relationship
      that is the basis of modern computer languages. In art, we find twinship in
      figure and ground, light and shade. Perhaps the most profound expressions of the
      Twinship Principle occur in psychology and spirituality: mind that is both local
      and nonlocal; the personal and the transpersonal; mortal and immortal; physical
      and immaterial; transcendent and immanent; sacred and profane. In all of these
      relationships, the entities illustrate the "coincidence of opposites." Like the
      poles of a magnet, they define each other and cannot exist without each other.
      Philosopher Alan Watts once said that the most profound metaphysical principle is
      that every inside has an outside, and every outside an inside. Is this the most
      important lesson of twins?

PMID- 9141285
TI  - Multiple sclerosis and hypnotherapy.

PMID- 9141287
TI  - Disappointed by biofeedback article.

PMID- 9141286
TI  - Experience with assisted suicide leads to advocacy.

PMID- 9141288
TI  - King County natural medicine clinic: public funding for integrated medicine.

PMID- 9141289
TI  - Illustration of a method for selecting research grant applications.
AB  - BACKGROUND: The method used by granting agencies to select applications they wish
      to support should be explicit, consistent, and fair, especially when the
      applications are diverse and controversial in nature, or when funds are limited,
      which is often the case. This study demonstrates the use of a method to satisfy
      such standards. METHODS: An expert committee appointed by the Swiss National
      Research Foundation planned and advertised a program for the evaluation of
      alternative therapies. The selection of applications to be supported was assisted
      by the use of Judgement Analysis. In the first phase, appropriate standards such
      as relevance to the program objectives and methodological adequacy were
      established. In the second phase, the relative weights attached to these
      standards by individual members were obtained by multiple linear regression
      analysis. In the third phase, a single common policy based on the standards that
      had been made explicit was applied to the choice of projects to be supported.
      RESULTS: 219 grant applications that proposed a variety of alternative treatments
      for various indications were reviewed; 17 were funded. CONCLUSIONS: The method of
      Judgment Analysis was acceptable to the experts, who were drawn from several
      disciplines and had diverse points of view. The method proved understandable and
      easy to use.

PMID- 9141290
TI  - Medical marijuana and its use by the immunocompromised.
AB  - BACKGROUND: Those immunocompromised by AIDS or cancer chemotherapy use marijuana
      to allay symptoms of their disease or treatment. Some researchers believe that
      marijuana may further suppress the immune system. A list of immunological hazards
      that may be present in marijuana was collated and assessed, and clinical
      recommendations regarding the use of marijuana by immunocompromised individuals
      were made. METHODS: Databases and other sources from 1964 to 1996 were searched
      using keywords (e.g., cannabinoids, cannabis, hemp, marijuana). This was
      supplemented by a manual search of bibliographies, nonindexed books, and
      journals, and by consultation with experts. All reports were analyzed for
      antecedent sources. Data validity was assessed by source, identification
      methodology, and frequency of independent observations. RESULTS: Substances
      implicated as potential immunological hazards in marijuana include endogenous
      constituents (cannabinoids, pyrolyzed gases, and particulates) and a longer list
      of exogenous contaminants, both natural (fungi and their metabolites) and
      synthetic (pesticides and adulterants). CONCLUSION: Burning of marijuana creates
      toxins of combustion. Particulate toxins (tars) are reduced by the use of
      vaporizer apparati. Gas-phase toxins are filtered by water pipes, but water pipes
      also filter some tetrahydrocannabinol, making this strategy counterproductive.
      Viable fungal spores in marijuana pose the greatest hazard to immunocompromised
      patients, though they can be sterilized by several methods. Pesticide residues
      and other adulterants may be present in black-market marijuana, but are absent in
      sources of marijuana that are approved by the Food and Drug Administration.

PMID- 9141291
TI  - Dynamical energy systems and modern physics: fostering the science and spirit of
      complementary and alternative medicine.
AB  - When systems theory is carefully applied to the concept of energy, some novel and
      far-reaching implications for modern physics and complementary medicine emerge.
      The heart of systems theory is dynamic interactions: systems do not simply act on
      systems, they interact with them in complex ways. By definition, systems at any
      level (e.g., physical, biological, social, ecological) are open to information,
      energy, and matter to varying degrees, and therefore interact with other systems
      to varying degrees. We first show how resonance between two tuning forks, a
      classic demonstration in physics, can be seen to reflect synchronized dynamic
      interactions over time. We then derive how the dynamic interaction of systems in
      mutual recurrent feedback relationships naturally create dynamic "memories" for
      their interactions over time. The mystery of how a photon (or electron) "knows"
      ahead of time whether to function as a particle or wave in the single slit/double
      slit quantum physics paradigm is potentially solved when energetic interactions
      inherent in the experimental system are recognized. The observation that energy
      decreases with the square of distance is shown not to be immutable when viewed
      from a dynamical energy systems perspective. Implications for controversial
      claims in complementary and alternative medicine, such as memory for molecules
      retained in water (homeopathy), remote diagnosis, and prayer and healing, are
      considered. A dynamical energy systems framework can facilitate the development
      of what might be termed "relationship consciousness," which has the potential to
      nurture both the science and spirit of complementary medicine and might help to
      create integrated medicine.

PMID- 9141292
TI  - A proposal for teaching critical thinking to students and practitioners of
      complementary medicine.
AB  - It can be argued that it is only possible to promote research in complementary
      and alternative medicine once the importance of critical thinking is understood.
      Critical thinking can be defined as (1) the adoption of a cautious approach to
      beliefs and claims, and (2) the process of analyzing beliefs to see whether they
      are valid and useful. The Research Council for Complementary Medicine has
      considerable experience teaching critical thinking to students and practitioners
      of complementary and alternative medicine. We use several tactics to ensure that
      such teaching has maximum impact: stressing that criticism does not pose a
      threat, using an interactive approach, avoiding abstract or esoteric discussions,
      giving examples from conventional medicine and from everyday life, and so on. The
      actual structure of a class involves a series of logical steps: stating the
      reasons for critical thinking, linking beliefs to belief-forming processes,
      linking beliefs about health to personal experience, explaining why personal
      experience can be unreliable, completing the "skeptical argument" that many
      health beliefs are unreliable, discussing the implications for practice, etc.
      Learning about critical thinking in such a manner can be an important
      prerequisite for undertaking or using the results of research.

PMID- 9141293
TI  - Managed care and alternative medicine: who will manage what, and how?

PMID- 9141295
TI  - Integrating complementary and alternative medicine into conventional medical
      practice.

PMID- 9141294
TI  - Stuart Hameroff, MD consciousness and microtubules in a quantum world. Interview
      by Bonnie Horrigan.

PMID- 9141296
TI  - Complementary medicine in the United Kingdom.

PMID- 9141297
TI  - "When I am lonely the mountains call me": the impact of sacred geography on
      Navajo psychological well being.
AB  - As we approach the twenty-first century, sacred geography continues to have a
      profound impact on Navajo psychological well being. This article explores the
      extent of the Navajo's bond with their homeland through an emphasis on orderly
      conditions in their world view, myths, and ceremonies. When traditional Navajos
      leave their homeland to pursue educational and professional endeavors or to seek
      biomedical treatment, a sense of emotional dislocation can undermine their
      success. The emotional trauma goes far beyond mere homesickness because it is
      based on an often unconscious sense of having violated the moral order of the
      universe. It is essential that mental health professionals respond with
      sensitivity to this issue by understanding the extent to which the sacred
      mountains and other landforms serve as a vital source of spiritual strength.

PMID- 9141298
TI  - Patterns of injury mortality among Athabascan Indians in interior Alaska 1977
      1987.
AB  - It was found that almost one-half of all Interior Alaska rural fatalities from
      thirty-six villages are due to unintentional and intentional injury. Drowning,
      motor vehicle crashes, hypothermia, fire, carbon monoxide poisoning and air
      transport crashes accounted for over 32% of all deaths; suicide and homicide
      account for over 15%. Many of these deaths are preventable.

PMID- 9141299
TI  - Psychosocial barriers to health promotion in an American Indian population.
AB  - Northern Plains Indians (N = 200) completed the Indian Specific Health Risk
      Appraisal and measures assessing beliefs about risk factors and personal risk.
      Participants rated personal risk optimistically, judged their risk factor
      standing as superior to that of their peers, and neglected to consider risk
      factor standing when appraising personal risk. Moreover, participants were often
      not improving their standing on risk factors they considered relevant to their
      health. Such biases in health beliefs may prevent health interventions from being
      successful.

PMID- 9141300
TI  - A survey of vocational rehabilitation counselors concerning American Indian and
      Alaska Native clients with alcohol and other drug abuse disorders.
AB  - Vocation rehabilitation (VR) counselors in states where many American Indians
      reside were questioned about the characteristics of their American Indian clients
      with alcoholism or drug abuse problems, and the kinds of services that were
      provided to them. A total of 124 counselors from 14 states responded to the
      survey. Twenty-seven of these respondents were employed in tribally operated VR
      projects in nine states.

PMID- 9141301
TI  - Ethical evaluation of hypnosis research: a survey of investigators and their
      institutional review boards.
AB  - We surveyed hypnosis researchers and Institutional Review Boards (IRBs) with
      regard to the ethical evaluation of research protocols. Researchers and IRB
      administrators were independently surveyed within the same institutions. Both
      objective and free response items were used to address substantive issues such as
      deception and at-risk populations, as well as practical matters such as
      paperwork. Parallel questions allowed a point-counterpoint between researchers
      and IRBs. Overall, the results suggest that IRBs do not treat hypnosis research
      differently than other types of research. We end with recommendations for
      facilitating interactions between hypnosis researchers and their IRBs.

PMID- 9141302
TI  - Mesmerism and Masonry: early historical interactions.
AB  - During the early years of animal magnetism, the Mesmeric and Masonic movements in
      France frequently shared membership, philosophical positions, ambience, and
      ritualistic style. There was even a proposal to establish a blend of the two to
      be called Mesmeric Masonry, although nothing came of that. This article documents
      such interactions and notes that important Mesmeric figures including Mesmer, the
      Puysegur brothers, Lafayette, and Gebelin, were also active Masons. Both
      movements were suppressed in France during the revolution, because they were
      considered to be threats to revolutionary goals.

PMID- 9141304
TI  - Fanciful interpretations of a musical dream.

PMID- 9141303
TI  - Hypnotic suggestion: a musical mathaphor.
AB  - Conceptually, hypnotizability has always been associated with the increase in
      suggestibility produced by hypnosis. In practice, hypnotizability is measured as
      suggestibility following a hypnotic induction. Our understanding of hypnosis and
      suggestion has been hampered by this discordance between the conceptual and
      operational definitions of hypnotizability. For example, despite hundreds of
      studies purporting to use standardized scales to assess hypnotizability, we know
      next to nothing about that construct, as it has been defined conceptually.
      Neither the hypothesis that it is a stable trait nor the hypothesis that it is
      modifiable have been tested in any study, and correlations between
      hypnotizability and other psychological or physiological variables have not yet
      been assessed. Conversely, we have learned much about hypnosis, suggestion, and
      suggestibility. Suggestibility has been measured on reliable and valid
      instruments, and we have abundant data on its stability, modifiability, and
      correlates. Hypnosis enhances suggestibility to a modest degree and increases the
      effectiveness of psychotherapy.

PMID- 9141305
TI  - Hypnosis as adjunctive therapy for multiple sclerosis: a progress report.
AB  - Several reports suggest that hypnosis can facilitate healing in various physical
      pathologies. This is a preliminary report, supported by three cases. They
      demonstrate that suggestion by a hypnotist of symptom improvement can be used
      beneficially in the treatment of the physical impairment caused by Multiple
      Sclerosis. The first patient, severely affected, had Multiple Sclerosis for over
      35 years. He had been wheelchair bound for many years. The second, recently
      diagnosed and minimally affected, had difficulty with balance and walked with the
      aid of a cane. The third, also minimally affected, reported pain in her right
      leg. All three showed improvement either immediately or within several weeks when
      the hypnotist suggested improvement or displacement of symptoms with the patients
      in hypnosis. No attempt was made to deal with psychodynamics or to suggest
      alternative symptoms to the patients. Symptom substitution did not occur. When
      symptoms improved, even slightly, these patients exhibited increased hopefulness.

PMID- 9141306
TI  - Morbid obesity, absorption, neuroticism, and the high risk model of threat
      perception.
AB  - We studied 70 morbidly obese patients, candidates for gastric exclusion surgery.
      We found that their mean absorption score was significantly lower and that their
      mean neuroticism score significantly higher than a matched control group. These
      results are consistent with predictions from the High Risk Model of Threat
      Perception (Wickramasekera, 1979, 1986, 1988, 1993a). People high in neuroticism
      are hypothesized to be hypersensitive to threat and, therefore, at greater risk
      for stress related psychobiological disorders. But if they are also low in
      absorption, they are hypothesized to have poor conscious perception of
      psychosocial threats and, therefore, they develop a very restricted range of
      psychosocial methods of coping with such threats. Consequently, lows may be
      mainly restricted to behavioral methods of coping like feeding and drinking to
      self-soothe unconscious aversive emotions associated with autonomic dysregulation
      and elevated parasympathetic tone. Their skeptical, rational, pragmatic cognitive
      style drives them to perceive medical surgical solutions to weight gain as more
      credible than psychosocial weight reduction programs.

PMID- 9141307
TI  - A study of objective functions for organs with parallel and serial architecture.
AB  - An objective function analysis when target volumes are deliberately enlarged to
      account for tumour mobility and consecutive uncertainty in the tumour position in
      external beam radiotherapy has been carried out. The dose distribution inside the
      tumour is assumed to have logarithmic dependence on the tumour cell density which
      assures an iso-local tumour control probability. The normal tissue immediately
      surrounding the tumour is irradiated homogeneously at a dose level equal to the
      dose D(R) delivered at the edge of the tumour. The normal tissue in the high dose
      field is modelled as being organized in identical functional subunits (FSUs)
      composed of a relatively large number of cells. Two types of organs--having
      serial and parallel architecture are considered. Implicit averaging over
      intrapatient normal tissue radiosensitivity variations is done. A function
      describing the normal tissue survival probability S0 is constructed. The
      objective function is given as a product of the total tumour control probability
      (TCP) and the normal tissue survival probability S0. The values of the dose D(R)
      which result in a maximum of the objective function are obtained for different
      combinations of tumour and normal tissue parameters, such as tumour and normal
      tissue radiosensitivities, number of cells constituting a normal tissue
      functional unit, total number of normal cells under high dose (D(R)) exposure and
      functional reserve for organs having parallel architecture. The corresponding TCP
      and S0 values are computed and discussed.

PMID- 9141308
TI  - Breast composition and radiographic breast equivalence.
AB  - The composition of the female breast is an elusive variable in screen-film
      mammography that has a vital role in determining both the radiographic image
      quality and breast radiation dose. Despite the large volume of research in
      mammography only two studies known to the author define the chemical composition
      of the two major breast constituents, fibrous glandular tissue and adipose
      tissue. Unfortunately there is not complete agreement between these two studies.
      Upon this basis, a variety of breast phantom materials have been suggested and
      developed. This paper examines the radiographic equivalence of some of these
      materials dealing notably with formulations given by Hammerstein et al and ICRU
      Report 44, as well as BR12, water, and lucite. Radiographic equivalence was
      calculated using a computer simulation of mammographic spectra (after the example
      of Birch and Marshall and Tucker et al, and fitted to available FDA data) applied
      to attenuation data of phantom materials, in turn based on elemental linear
      attenuation coefficient data. A software algorithm was written that iteratively
      calculates the thickness of a nominated material required to match the
      attenuation of another material of particular thickness. The equivalence of 2-8
      cm of lucite to various phantom materials was calculated for molybdenum target,
      molybdenum filter (Mo/Mo) x-ray beams from 25 to 35 kVp and for Mo/Rh and Rh/Rh
      beams from 27 to 35 kVp. It was found that for Mo/Mo beams the equivalent
      thickness of breast phantom material for certain thicknesses of lucite was
      largely independent of x-ray beam energy with the range of thickness equivalences
      being less than 3% at 8 cm of lucite and less than 0.5% at 2 cm of lucite. The
      RMI 156 breast phantom was found to be equivalent to 42 mm of Hammerstein et al.
      50% glandular/50% adipose phantom material for Mo/Mo beams at 27 kVp, increasing
      to 43 mm for the range of Rh/Rh beams. While some questions remain on the
      accuracy of the present composition of breast constituents, it is clear that
      various breast compositions can be successfully simulated by using an appropriate
      thickness of lucite material. The use of lucite breast phantoms is then seen as
      an effective and reliable way of evaluating mammographic image quality and for
      calculating breast dose for varying required breast compositions.

PMID- 9141309
TI  - The validity of using radiographic film for radiotherapy dosimetry.
AB  - Radiographic film is routinely used to obtain dosimetric information about
      therapy treatment beams. One source of inaccuracy is the variability of the
      chemical processing of the radiographic film. Several processors, film types and
      two sources (light and x-rays) were used to investigate the reproducibility of
      film processing for valid film dosimetry. Particular attention is paid to films
      commonly used in radiation therapy. The results suggest that for this series of
      film, given the same exposure, the variability in processing may result in an
      error of +/- 3.3% in optical density, which would lead to an error of +/- 4.4% in
      indicated dose. This level of inaccuracy is typical for both point and relative
      dose estimates. These results indicate that film should not be used as a point or
      relative dosimeter, unless the combination of film type, exposure, processing and
      reading have been specifically validated.

PMID- 9141310
TI  - Medical physics is alive and well and growing in South East Asia.
AB  - In recent years there has been a significant economic growth in South East Asia,
      along with it a concurrent development of medical physics. The status of four
      countries--Malaysia, Thailand, the Philippines and Indonesia are presented.
      Medical physicists in these countries have been experiencing the usual problems
      of lack of recognition, low salaries, and insufficient facilities for education
      and training opportunities. However the situation has improved recently through
      the initiative of local enthusiastic medical physicists who have started MS
      graduate programs in medical physics and begun organizing professional activities
      to raise the profile of medical physics. The tremendous support and catalytic
      roles of the American Association of Physicists in Medicine (AAPM) and
      international organizations such as International Organization for Medical
      Physics (IOMP), International Atomic Energy Agency (IAEA), World Health
      Organization (WHO), and International Center for Theoretical Physics (ICTP) have
      been instrumental in achieving progress. Contributions by these organizations
      include co-sponsorship of workshops and conferences, travel grants, medical
      physics libraries programs, and providing experts and educators. The demand for
      medical physicists is expected to rise in tandem with the increased emphasis on
      innovative technology for health care, stringent governmental regulation, and
      acceptance by the medical community of the important role of medical physicists.

PMID- 9141311
TI  - Design of a Web interface for anatomical images.
AB  - Interactive documents for use with the World Wide Web have been developed for
      viewing multi-dimensional radiographic and visual images of human anatomy,
      derived from the Visible Human Project. Emphasis has been placed on user
      controlled features and selections. The purpose was to develop an interface which
      was independent of host operating system and browser software which would allow
      viewing of information by multiple users. The interfaces were implemented using
      HyperText Markup Language (HTML) forms, C programming language and Perl scripting
      language. Images were pre-processed using ANALYZE and stored on a Web server in
      CompuServe GIF format. Viewing options were included in the document design, such
      as interactive thresholding and two-dimensional slice direction. The interface is
      an example of what may be achieved using the World Wide Web. Key applications
      envisaged for such software include education, research and accessing of
      information through internal databases and simultaneous sharing of images by
      remote computers by health personnel for diagnostic purposes.

PMID- 9141312
TI  - Seniors-on-line: introducing older people to technology.
AB  - Retired Engineers are playing an important role in ensuring that older people are
      not excluded from the benefits of technological advances. Technology is playing
      an increasingly important role in the lives of older people as it is incorporated
      into assistive devices, home security, access to health care, banking,
      communication and many other areas. However, if older people are unfamiliar with
      new technologies and find them daunting, they may not benefit fully from these
      advances. In order to minimize difficulties arising from unfamiliarity with
      technology, an introductory computer course was offered to people aged 55 and
      over. Teaching methods appropriate to the needs of older people were used: small
      classes, students and instructors from same age cohort, slow pace of presentation
      and ample opportunity to ask questions. Retired Engineers make up the majority of
      instructors. Three hundred and sixty nine older people have participated in the
      course and most plan to continue using a computer.

PMID- 9141313
TI  - Technical considerations for the use of independent collimators to achieve
      optimal photon field matching in radiotherapy.
AB  - The dose uniformity across a junction between two abutting photon fields can be
      optimised by creating non-divergent field edges using independent collimators.
      Current linear accelerator specifications for the positional accuracy of such
      collimators are not rigorous enough to ensure that a clinically acceptable match
      is produced. Confirmation of the junction dose is required prior to clinical use
      and additional quality assurance is necessary to ensure that the strict
      requirement for positional accuracy is maintained.

PMID- 9141314
TI  - Field programmable gate array in a fast 256-channel data acquisition system.
AB  - We describe an FPGA (Field Programmable Gate Array) controlled fast data
      acquisition system with 256 channels suitable for high resolution
      electrocardiographic (ECG), electrogastrographic (EGG) and late potential (LP)
      recordings. The A/D converter provides 800ns conversion time with 12 bits. The
      S11W, a 16 bit, parallel, I/O interface, is used to connect the data acquisition
      device to a portable SPARC-compatible computer. With only one A/D converter, we
      have achieved 2 kHz sampling rate for each channel and more than 1MB/s overall by
      using an overlapping delay technique. Channel parameters can be selected
      independently from one of eight gains ranging from 50 to 10,000, and one of three
      filters ("ECG" 0.05-120Hz, "EGG" 0.001-1Hz and "LP" 60-1kHz). There are eight
      programmable sampling frequencies from 2Hz to 2kHz. The system is fully battery
      operated and protected from the defibrillation high voltages to meet the safety
      requirements. The acquisition system can be widely used in medical research and
      clinical applications.

PMID- 9141315
TI  - Laparoscopic staging and treatment of gastric cancer.

PMID- 9141316
TI  - Six challenges in measuring the quality of health care.
AB  - Quality monitoring is becoming an accepted method for purchasers, patients, and
      providers to evaluate the value of health care expenditures. Important advances
      in the science of quality measurement have occurred over the past decade, but
      many challenges remain to be addressed so that quality monitoring may realize its
      potential as a counterforce to the demands of cost containment. This paper
      describes six such challenges (balancing perspectives, defining accountability,
      establishing criteria, identifying reporting requirements, minimizing conflict
      between financial and quality goals, and developing information systems) and
      proposes some ways in which the public and private sectors might collaborate to
      respond effectively.

PMID- 9141317
TI  - How do we measure quality?

PMID- 9141318
TI  - Who is holding whom accountable for quality?
AB  - The debate over accountability for managed care quality is occurring everywhere,
      from Congress and state legislatures to courtrooms and boardrooms. This paper
      reviews a variety of today's techniques for holding managed care answerable for
      quality, ranging from those grounded in the law to more market-based approaches,
      including accreditation and commerce in data about plan performance. Today, there
      is some dissonance between purchasers' rhetoric about quality and their actual
      buying behavior. Eventually the discussion of accountability for quality may
      really be joined when the baby boomers become the consumers of this system and
      not just its financiers.

PMID- 9141319
TI  - The role of states in accountability for quality.

PMID- 9141320
TI  - A vision of quality in health care delivery.
AB  - Empirical evidence is thin, so one must reply on informed judgment, common sense,
      and theory when describing a high-quality health plan. Using this approach, a
      high-quality health plan would be characterized by excellence in the following
      areas: physician selection and development; health improvement; information
      systems; continuous quality improvement; cooperation with health care purchasers;
      alignment of financial incentives and appropriate capitation; and patient
      involvement. High-quality health plans would be nurtured by a national context in
      which medical education recognizes managed care and quality measurement, risk
      adjusted premiums are the norm, competition is managed, and government has a
      limited role.

PMID- 9141321
TI  - Changing with the times: the views of Bruce C. Vladeck. Interview by John K.
      Iglehart.

PMID- 9141322
TI  - Quality lessons for public policy: a health plan's view.

PMID- 9141323
TI  - Promoting quality: a public policy view.

PMID- 9141324
TI  - Compensation and quality: a physician's view.

PMID- 9141325
TI  - Managing utilization management: a purchaser's view.

PMID- 9141326
TI  - Smart technology, stunted policy: developing health information networks.
AB  - Ideally, computer networks should help raise the quality of health care, reduce
      its cost, and enable consumers and providers to make smarter decisions. But
      government and the private sector have failed to resolve such critical problems
      as the protection of medical privacy and production of reliable comparative data
      on plans and providers. While individual enterprises are building information
      networks, community networks serving public purposes have lagged. An information
      revolution in health care is the making, but the hope that it will allow
      consumers and providers to make smarter choices is still far from being realized.

PMID- 9141327
TI  - Health information systems and the role of state government.
AB  - State government entities have created a range of innovative electronic
      information systems to support their diverse and evolving roles in the health
      care system. Primary goals of these initiatives include improvement of
      traditional public health programs, meaningful oversight of providers,
      simplification of administrative procedures, and support of state purchasing
      decisions. We establish a taxonomy of state efforts, describing primary
      capabilities to (1) provide meaningful data to state decisionmakers; (2)
      disseminate information to purchasers and consumers; (3) coordinate and improve
      government services; (4) establish mechanisms for electronic transactions; and
      (5) support telemedicine services. Reductions in the costs of technology and use
      of the Internet have dramatically increased state capabilities in recent years.
      Both the successes and failures of existing programs offer important lessons for
      states that are initiating new electronic communication initiatives.

PMID- 9141328
TI  - Physician earnings at risk: an examination of capitated contracts.

PMID- 9141329
TI  - The surge in Medicare managed care: an update.

PMID- 9141330
TI  - Ten ways HMOs have changed during the 1990s.
AB  - The same forces that encouraged the expansion of managed care also brought about
      change in health maintenance organizations (HMOs). Using data from annual surveys
      of the Association of American Health Plans and other sources, this paper
      examines ten major changes in the HMO industry during the 1990s, including the
      growth of for-profit plans and the relative decline of nonprofits; the shift from
      vertically integrated group/staff models to virtually integrated individual
      practice associations/network models; industry consolidation through mergers and
      acquisitions; increased patient cost sharing; and the shift to capitation payment
      of primary care physicians. Current research is unable to show whether these
      changes have led to improved quality of care or patient satisfaction.

PMID- 9141331
TI  - The politics of the Health Insurance Portability and Accountability Act.

PMID- 9141332
TI  - Assessing strategies for quality improvement.

PMID- 9141333
TI  - Balancing cost and quality in fee-for-service versus managed care.

PMID- 9141334
TI  - Managed care, rationing, and quality: a tangled relationship.

PMID- 9141335
TI  - "Miracle and wonder": the AMA embraces quality measurement.

PMID- 9141336
TI  - Restoring the ethical balance in health care.

PMID- 9141337
TI  - Maternity experiences in a managed care organization.
AB  - We conducted a telephone survey of female managed care enrollees who recently had
      a normal vaginal delivery to examine the relationship between hospital length-of
      stay and maternal characteristics, pregnancy factors, length-of-stay preferences,
      and postdischarge experiences. Results indicated that length-of-stay varied by
      maternal characteristics and pregnancy factors. Length-of-stay and maternal or
      newborn readmissions were not statistically associated. Most respondents reported
      that they would be willing to go home within twenty-four hours after future
      deliveries if additional services were provided. Emphasis should be placed on
      which services can be provided to prepare and assist mothers through the
      perinatal period.

PMID- 9141338
TI  - Satisfaction and choice: a view from the plans.
AB  - Community-wide surveys have demonstrated that managed care enrollees tend to
      express higher satisfaction with their health plan if they have been given the
      opportunity to make a choice between managed care and fee-for-service plans. This
      DataWatch shows similar results with plan-specific data, even for enrollees whose
      plan benefits include coverage for out-of-network services. That is, what matters
      seems to be choice at the time of enrollment, not at the point of service.
      Further, in the practical application of ranking plans on overall enrollee
      satisfaction, choice appears to be a more important influence than other factors
      that may receive attention, including enrollees' health status. We discuss this
      phenomenon with respect to competition and strategy in the managed care
      marketplace.

PMID- 9141339
TI  - Will quality report cards help consumers?
AB  - This study assesses the relationship between the salience of quality information
      and how well it is understood by consumers. The analysis is based on survey data
      and content analysis from focus-group data (104 participants). The findings show
      that poorly understood indicators are viewed as not useful. Consumers often do
      not understand quality information because they do not understand the current
      health care context. All of this suggests that salience alone is not sufficient
      to determine which indicators should be included in report cards.

PMID- 9141340
TI  - Choosing a health plan: what information will consumers use?
AB  - Employers and policymakers are looking for ways to encourage competition among
      health plans, thus lowering costs and improving quality. Employers hope to foster
      competition among health plans by creating standardized measures of quality that
      supplement the traditional benefits and cost information employees use to compare
      plans and make choices. This DataWatch examines employees' interest in
      standardized measures of plan performance. Results from a survey of Massachusetts
      state employees show that cost and benefit information receive high rankings, but
      certain plan performance information does not.

PMID- 9141341
TI  - Chronic care costs in managed care.
AB  - This DataWatch presents estimates of the health care costs for all adults who
      were continuously enrolled in a large staff-model health maintenance organization
      (HMO) during 1992. More than one-third of these adults were diagnosed with at
      least one chronic condition in 1992, and costs for this population are at least
      twice those of the population without chronic conditions. A diagnosis of a
      chronic condition results in an expected increase in costs of 80 percent-300
      percent, depending on age, sex, and chronic condition profile. Previous studies
      of the costs of chronic illness have focused on the fee-for-service sector. As
      managed care continues to grow, it is important that economic analyses focus on
      this market segment.

PMID- 9141342
TI  - Quality assurance for Medicaid managed care.

PMID- 9141343
TI  - An open letter to the president on quality.

PMID- 9141344
TI  - Hospital conversions and uncompensated care.

PMID- 9141345
TI  - Outcomes following childbirth.

PMID- 9141346
TI  - Trusting managed care: unbiased data needed.

PMID- 9141347
TI  - Women's primary care.

PMID- 9141348
TI  - Helicobacter pylori--a review.

PMID- 9141349
TI  - To which extent Ureaplasma urealyticum (mycoplasma) genital infection is
      responsible for male infertility.

PMID- 9141350
TI  - Chloroquine--induced recurrent psychosis (brief report).

PMID- 9141351
TI  - Leprosy resistant to multi-drug-therapy (MDT) successfully treated with
      ampicillin-sulbactam combination--(a case report).
AB  - A 50 year male developed a discoid lesion of leprosy on the face. Inspite of
      Dapsone 100 mg/day and Rifampicin 600 mgm per day the disease spread to both
      sides of the face and forehead. It became worse with Prednisolone and
      Clofazimine. It cleared completely when Sultamicillin was added to the latter.
      This seems to be the first patient of leprosy to be treated with this combination
      and reported.

PMID- 9141352
TI  - Retained portion of latex glove during femoral nailing. Case report.
AB  - A case of retained glove during Kuntscher intramedullary nailing is described. An
      abscess around the glove could have lead to osteomyelitis. One need to be
      cautious feeling the top end of the nail while femoral nailing to avoid such a
      complication.

PMID- 9141353
TI  - Targeting G protein-coupled receptor kinases to their receptor substrates.

PMID- 9141354
TI  - Characterization of volume-sensitive organic osmolyte efflux and anion current in
      Xenopus oocytes.
AB  - Cell swelling activates an outwardly rectifying anion current in numerous
      mammalian cell types. An extensive body of evidence indicates that the channel
      responsible for this current is the major pathway for volume regulatory organic
      osmolyte loss. Cell swelling also activates an outwardly rectifying anion current
      in Xenopus oocytes. Unlike mammalian cells, oocytes allow the direct study of
      both swelling-activated anion current and organic osmolyte efflux under nearly
      identical experimental conditions. We therefore exploited the unique properties
      of oocytes in order to examine further the relationship between anion channel
      activity and swelling-activated organic osmolyte transport. Swelling-activated
      anion current and organic osmolyte efflux were studied in parallel in batches of
      oocytes obtained from single frogs. The magnitude of swelling-activated anion
      current and organic osmolyte efflux exhibited a positive linear correlation. In
      addition, the two processes had similar pharmacological characteristics and
      activation, rundown and reactivation kinetics. The present study provides further
      strong support for the concept that the channel responsible for swelling
      activated Cl- efflux and the outwardly rectifying anion conductance is also the
      major pathway by which organic osmolytes are lost from vertebrate cells during
      regulatory volume decrease.

PMID- 9141355
TI  - Molecular dissection of the large mechanosensitive ion channel (MscL) of E. coli:
      mutants with altered channel gating and pressure sensitivity.
AB  - In the search for the essential functional domains of the large mechanosensitive
      ion channel (MscL) of E. coli, we have cloned several mutants of the mscL gene
      into a glutathione S-transferase fusion protein expression system. The resulting
      mutated MscL proteins had either amino acid additions, substitutions or deletions
      in the amphipathic N-terminal region, and/or deletions in the amphipathic central
      or hydrophilic C-terminal regions. Proteolytic digestion of the isolated fusion
      proteins by thrombin yielded virtually pure recombinant MscL proteins that were
      reconstituted into artificial liposomes and examined for function by the patch
      clamp technique. The addition of amino acid residues to the N-terminus of the
      MscL did not affect channel activity, whereas N-terminal deletions or changes to
      the N-terminal amino acid sequence were poorly tolerated and resulted in channels
      exhibiting altered pressure sensitivity and gating. Deletion of 27 amino acids
      from the C-terminus resulted in MscL protein that formed channels similar to the
      wild-type, while deletion of 33 C-terminal amino acids extinguished channel
      activity. Similarly, deletion of the internal amphipathic region of the MscL
      abolished activity. In accordance with a recently proposed spatial model of the
      MscL, our results suggest that (i) the N-terminal portion participates in the
      channel activation by pressure, and (ii) the essential channel functions are
      associated with both, the putative central amphipathic alpha-helical portion of
      the protein and the six C-terminal residues RKKEEP forming a charge cluster
      following the putative M2 membrane spanning alpha-helix.

PMID- 9141356
TI  - Transmembrane insertion of the colicin Ia hydrophobic hairpin.
AB  - Colicin Ia is a bactericidal protein that forms voltage-dependent, ion-conducting
      channels, both in the inner membrane of target bacteria and in planar bilayer
      membranes. Its amino acid sequence is rich in charged residues, except for a
      hydrophobic segment of 40 residues near the carboxyl terminus. In the crystal
      structure of colicin Ia and related colicins, this segment forms an alpha-helical
      hairpin. The hydrophobic segment is thought to be involved in the initial
      association of the colicin with the membrane and in the formation of the channel,
      but various orientations of the hairpin with respect to the membrane have been
      proposed. To address this issue, we attached biotin to a residue at the tip of
      the hydrophobic hairpin, and then probed its location with the biotin-binding
      protein streptavidin, added to one side or the other of a planar bilayer.
      Streptavidin added to the same side as the colicin prevented channel opening.
      Prior addition of streptavidin to the opposite side protected channels from this
      effect, and also increased the rate of channel opening; it produced these effects
      even before the first opening of the channels. These results suggest a model of
      membrane association in which the colicin first binds with the hydrophobic
      hairpin parallel to the membrane; next the hairpin inserts in a transmembrane
      orientation; and finally the channel opens. We also used streptavidin binding to
      obtain a stable population of colicin molecules in the membrane, suitable for the
      quantitative study of voltage-dependent gating. The effective gating charge thus
      determined is pH-independent and relatively small, compared with previous results
      for wild-type colicin Ia.

PMID- 9141357
TI  - ATP-sensitive voltage- and calcium-dependent chloride channels in sarcoplasmic
      reticulum vesicles from rabbit skeletal muscle.
AB  - Chloride channels in the sarcoplasmic reticulum (SR) are thought to play an
      essential role in excitation-contraction (E-C) coupling by balancing charge
      movement during calcium release and uptake. In this study the nucleotide
      sensitivity of Cl- channels in the SR from rabbit skeletal muscle was
      investigated using the lipid bilayer technique. Two distinct ATP-sensitive Cl-
      channels that differ in their conductance and kinetic properties and in the
      mechanism of ATP-induced channel inhibition were observed. The first, a
      nonfrequent 150 pS channel was inhibited by trans (luminal) ATP, and the second,
      a common 75 pS small chloride (SCl) channel was inhibited by cis (cytoplasmic)
      ATP. In the case of the SCl channel the ATP-induced reversible decline in the
      values of current (maximal current amplitude, Imax and integral current, I') and
      kinetic parameters (frequency of opening FO, probability of the channel being
      open PO, mean open TO and closed Tc times) show a nonspecific block of the
      voltage- and Ca2+-dependent SCl channel. ATP was a more potent blocker from the
      cytoplasmic side than from the luminal side of the channel. The SCl channel block
      was not due to Ca2+ chelation by ATP, nor to phosphorylation of the channel
      protein. The inhibitory action of ATP was mimicked by the nonhydrolyzable
      analogue adenylylimidodiphosphate (AMP-PNP) in the absence of Mg2+. The
      inhibitory potency of the adenine nucleotides was charge dependent in the
      following order ATP4- > ADP3- > > > AMP2-. The data suggest that ATP-induced
      effects are mediated via an open channel block mechanism. Modulation of the SCl
      channel by [ATP]cis and [Ca2+]cis indicates that (i) this channel senses the
      bioenergetic state of the muscle fiber and (ii) it is linked to the ATP-dependent
      cycling of the Ca2+ between the SR and the sarcoplasm.

PMID- 9141359
TI  - Protein kinase C-independent correlation between P-glycoprotein expression and
      volume sensitivity of Cl- channel.
AB  - The possible correlation between P-glycoprotein (PGP) and volume-sensitive Cl-
      channel was examined in a pair of cell lines: a subline of the human epidermoid
      KB cell (KB-3-1) and the corresponding MDR1-transfected cell line (KB-G2).
      Western blot analysis and indirect immunofluorescence studies indicated that KB
      G2, but not KB-3-1, exhibits the PGP expression. Patch-clamp whole-cell
      recordings showed that osmotic swelling activates Cl- currents not only in PGP
      expressing but also in PGP-lacking cells. The amplitude of the maximal current
      was indistinguishable between both cells. Activation of protein kinase C (PKC) or
      loading with a PKC inhibitor failed to affect the swelling-induced activation of
      the Cl- currents in both cells. The relation between whole-cell Cl- currents and
      cell size measured simultaneously showed that volume sensitivity of the Cl-
      channel was augmented by the PGP expression irrespective of the activity of PKC
      on the plasma membrane. A similar increase in volume sensitivity of the Cl-
      channel was also induced by the expression of the ATP hydrolysis-deficient PGP
      mutant, K433M. We conclude that P-glycoprotein does not represent the volume
      sensitive Cl- channel but that its expression modulates volume sensitivity of the
      Cl- channel in a manner independent of its ATPase activity or of the protein
      kinase C activity.

PMID- 9141358
TI  - Cross talk of bumetanide-sensitive and HCO3--dependent transporters activated by
      IBMX in renal epithelial A6 cells.
AB  - We studied cAMP-dependent regulation of ion transport in aldosterone-untreated
      renal epithelial A6 cells by measuring short-circuit current (Isc). Biphasic
      increases in Isc, a transient phase followed by a sustained one, were elicited in
      response to 1 mm 3-isobutyl-1-methylxanthine (IBMX, an inhibitor of
      phosphodiesterase) which increased cytosolic cAMP concentration. IBMX increased
      the apical Cl- conductance. The sustained phase of Isc induced by IBMX was
      reduced by 50 microM bumetanide (Na+/K+/2 Cl- cotransporter inhibitor) or 100
      microM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS, an inhibitor of Cl
      /HCO3- exchanger). Under the normal condition, the inhibitory effect of
      bumetanide was much larger than that of DIDS. On the other hand, under a low Cl-
      condition, the effect of DIDS was more effective than that of bumetanide.
      Further, under a Cl--free condition Na+/HCO3- symporter contributed to the IBMX
      generated Isc. Taken together, our observations suggest that in A6 cells (i) IBMX
      stimulates Cl- secretion associated with an increase in apical Cl- conductances,
      (ii) the ionic components to generate the IBMX-induced Isc are mainly maintained
      by bumetanide-sensitive Na+/K+/2 Cl- cotransporter and DIDS-sensitive Cl-/HCO3-
      exchanger, (iii) Cl-/HCO3- exchanger coupled to Na+/HCO3- symporter under a low
      Cl- condition or Na+/HCO3- symporter under a Cl--free condition contributes to
      the IBMX-induced Isc, compensating for diminishment of the Na+/K+/2Cl-
      cotransporter-mediated Cl- secretion, (iv) IBMX increases Cl- and HCO3-
      conductances in the apical membrane.

PMID- 9141360
TI  - Activation of inwardly rectifying potassium channels by muscarinic receptor
      linked G protein in isolated human ventricular myocytes.
AB  - Muscarinic receptor-linked G protein, Gi, can directly activate the specific K+
      channel (IK(ACh)) in the atrium and in pacemaker tissues in the heart. Coupling
      of Gi to the K+ channel in the ventricle has not been well defined. G protein
      regulation of K+ channels in isolated human ventricular myocytes was examined
      using the patch-clamp technique. Bath application of 1 microM acetylcholine (ACh)
      reversibly shortened the action potential duration to 74.4 +/- 12.1% of control
      (at 90% repolarization, mean +/- SD, n = 8) and increased the whole-cell membrane
      current conductance without prior beta-adrenergic stimulation in human
      ventricular myocytes. The ACh effect was reversed by atropine (1 microM). In
      excised inside-out patch configurations, application of GTPgammaS (100 microM) to
      the bath solution (internal surface) caused activation of IK(ACh) and/or the
      background inwardly-rectifying K+ channel (IK1) in ventricular cell membranes.
      IK(ACh) exhibited rapid gating behavior with a slope conductance of 44 +/- 2 pS
      (n = 25) and a mean open lifetime of 1.8 +/- 0.3 msec (n = 21). Single channel
      activity of GTPgammaS-activated IK1 demonstrated long-lasting bursts with a slope
      conductance of 30 +/- 2 pS (n = 16) and a mean open lifetime of 36.4 +/- 4.1 msec
      (n = 12). Unlike IK(ACh), G protein-activated IK1 did not require GTP to maintain
      channel activity, suggesting that these two channels may be controlled by G
      proteins with different underlying mechanisms. The concentration of GTP at half
      maximal channel activation was 0.22 microM in IK(ACh) and 1.2 microM in IK1.
      Myocytes pretreated with pertussis toxin (PTX) prevented GTP from activating
      these channels, indicating that muscarinic receptor-linked PTX-sensitive G
      protein, Gi, is essential for activation of both channels. G protein-activated
      channel characteristics from patients with terminal heart failure did not differ
      from those without heart failure or guinea pig. These results suggest that ACh
      can shorten the action potential by activating IK(ACh) and IK1 via muscarinic
      receptor-linked Gi proteins in human ventricular myocytes.

PMID- 9141361
TI  - Properties of two multisubstate Cl- channels from human syncytiotrophoblast
      reconstituted on planar lipid bilayers.
AB  - We describe the first successful reconstitution of placental ionic channels on
      planar lipid bilayers. An apical plasma membrane-enriched vesicle fraction from
      human syncytiotrophoblast at term was prepared by following isotonic agitation,
      differential centrifugation, and Mg2+-induced selective precipitation of
      nonapical membranes, and its purity was assessed by biochemical and morphological
      marker analysis. We have already reported that, unlike previous patch-clamp
      studies, nonselective cation channels were incorporated in most cases, a result
      consistent with the higher permeability for cations as compared with Cl- and with
      the low apical membrane potential difference at term revealed by fluorescent
      probe partition studies, and microelectrode techniques. In this paper, we report
      that Cl--selective channels were incorporated in 4% of successful reconstitutions
      (14 out of 353) and that their analysis revealed two types of activity. One of
      them was consistent with a voltage-dependent, 100-pS channel while the other was
      consistent with the lateral association of 47-pS conductive units, giving rise to
      multibarrelled, DIDS-sensitive channels of variable conductance (300 to 650 pS).
      The latter displayed a very complex behavior which included cooperative gating of
      conductive units, long-lived substates, voltage-dependent entry into an apparent
      inactivated state, and flickering activity. The role of the reported Cl- channels
      in transplacental ion transport and/or syncytium homeostasis remains to be
      determined.

PMID- 9141363
TI  - Ulcerating necrobiosis lipoidica resolving in response to cyclosporine-A.
AB  - Necrobiosis lipoidica often fails to respond adequately to therapy with topical
      and intralesional corticosteroids, or to systemic medications like niacinamide
      and pentoxifylline (Trental). On the basis of unpublished work which showed a
      predominance of T helper cells in lesions of necrobiosis lipoidica, and recalling
      the case of a woman whose necrobiosis lipoidica improved after she was started on
      cyclosporine for a renal transplant, systemic cyclosporine was successfully used
      in the cases of two young women who had insulin-dependent diabetes and were
      disfigured by severe, ulcerating necrobiosis lipoidica on the anterior lower
      legs. Response to treatment was monitored with photographs. In both cases the
      ulcers resolved, and remained in remission after cyclosporine was stopped.

PMID- 9141362
TI  - Angiotensin II receptors: localization of type I and type II in rat epididymides
      of different developmental stages.
AB  - Previous studies from our laboratory have provided evidence for the existence of
      a local renin-angiotensin system in the rat epididymis. Evidence has also
      accumulated, indicating that locally formed angiotensin II from the rat
      epididymis may play a paracrine and/or autocrine role in regulating epididymal
      electrolyte and fluid transport. In the present study, specific anti-peptide
      antibodies against the second extracellular loops of angiotensin II type I (AT1)
      and type II (AT2) receptors were used to localize immunocytochemically these
      receptors in the rat cauda epididymides of three developmental stages, namely,
      immature (2-week), early mature (6-week) and fully mature (10-week). The
      immunostaining intensity for AT1 receptors was found to be stronger than that for
      AT2 receptors throughout rat epididymides of all stages. However, the
      immunostaining for both AT1 and AT2 receptors observed in the fully mature rat
      epididymis was much more intense than that observed in the epididymides of the
      two younger stages. While the immunostaining for both AT1 and AT2 receptors in
      the younger rat epididymides appeared to be distributed in both basal and apical
      regions, the immunostaining in the fully mature epididymis was predominantly
      localized in the basal region. The present finding of the differential patterns
      of angiotensin II receptor immunoreactivity in three different stages of the rat
      epididymis may reflect the fine tuning of rat epididymal function by angiotensin
      II, acting as a paracrine or autocrine agent, during the course of development.

PMID- 9141364
TI  - The highly effective use of topical zinc pyrithione in the treatment of
      psoriasis: a case report.
AB  - Psoriasis is a common condition which, at times, can be difficult to treat.
      Patients with psoriasis face many social challenges and can suffer a great deal
      with their disease. As a result, any new topical agent is a welcomed addition to
      our therapeutic armamentarium. We present here a report of a case using a novel
      topical preparation of zinc pyrithione for the treatment of psoriasis. Topical
      zinc pyrithione appears to be a safe and effective treatment for psoriasis.

PMID- 9141365
TI  - Painful leg lesions: a case report.
AB  - We describe a case of Loefgren's syndrome where the characteristic history and
      physical exam allowed for the provisional diagnosis to be made in the emergency
      department. The diagnosis was subsequently confirmed by hilar lymph node biopsy
      demonstrating noncaseating granulomas. The prognosis and treatment are briefly
      reviewed.

PMID- 9141366
TI  - Malignant melanoma simulating a seborrheic keratosis: a case report.
AB  - This is a case report of malignant melanoma presenting with both clinical and
      histopathologic features of a seborrheic keratosis. Not a rare phenomenon, this
      report emphasizes the importance of biopsy to evaluate apparent seborrheic
      keratoses. We believe that this phenomenon is best considered a presentation of
      melanoma. Diminished routine histopathologic evaluation of apparent seborrheic
      keratoses may well increase the number of mistaken diagnoses in such cases.

PMID- 9141367
TI  - What's bugging you now? Tetranychus urticae.

PMID- 9141368
TI  - Deep penetrating nevus.

PMID- 9141369
TI  - The changing format of web-based medical information.

PMID- 9141370
TI  - Mechanical efficiency in hypertrophic cardiomyopathy assessed by positron
      emission tomography with carbon 11 acetate.
AB  - This study was performed to assess the relation between the regional work and
      oxidative metabolism in hypertrophic cardiomyopathy (HCM). By using carbon 11
      acetate as a tracer of myocardial blood flow (%A(0)) and oxygen consumption (k
      value), 12 patients with HCM with asymmetric septal hypertrophy and 10 normal
      subjects were studied. Regional work rate (RWR) of the left ventricle was
      estimated by wall stress and wall thickness. %A(0) in hypertrophied septum was
      similar to that in nonhypertrophied free wall (92.6% +/- 2.8% vs 93.5% +/- 3.8%;
      p = not significant). However, oxygen consumption was significantly lower in
      hypertrophied septum than in nonhypertrophied free wall (0.043 +/- 0.011 vs 0.057
      +/- 0.013 min(-1); p < 0.001). The k value in nonhypertrophied free wall was
      similar to the value observed in normal subjects (0.062 +/- 0.013). Average
      values for RWR in hypertrophied septum, nonhypertrophied free wall, and normal
      subjects were 0.26 +/- 0.07,0.62 +/- 0.02,and 1.98 +/- 0.15 J/cm3/ min,
      respectively. Furthermore, the analysis of covariance, in which the effect of RWR
      was removed as a covariate, revealed that the overall RWR-corrected k value was
      much larger in patients with HCM (0.109 vs 0.062, p < 0.0001) than expected from
      the decreased regional myocardial work, suggesting that there was a diffused
      inefficiency in oxygen consumption. We concluded, therefore, that the relative
      value of oxidative metabolism in patients with HCM is significantly higher than
      that of the normal subjects, suggesting the presence of reduced mechanical
      efficiency.

PMID- 9141371
TI  - Sublingual nitrates during head-up tilt testing for the diagnosis of vasovagal
      syncope.
AB  - Pharmacologic stimulation during head-up tilt test (HUT) is used to increase the
      diagnostic yield of the test to detect vasovagal syncope. Reported lack of
      specificity of stimulation with intravenous isoproterenol has made a
      pharmacologic alternative desirable. Because nitrates are known to cause syncope
      of a vasovagal origin, we administered sublingual nitrates after classic tilt
      test in 32 patients with a history of typical vasovagal syncope and 20 healthy
      volunteers to assess the sensitivity, specificity, and accuracy of this new HUT
      technique. During the classic HUT four (13%) patients had syncope; after
      administration of sublingual nitrates, this number increased to 28 (87%). In the
      control group no subject had syncope during classic HUT, whereas during nitrate
      administration six (30%) had syncope. Sublingual nitrate stimulated HUT revealed
      a maximum accuracy of 83% at a cutoff point of 11 minutes, giving a sensitivity
      of 81% and specificity of 85%. Sublingual nitrate administration increased the
      accuracy of HUT in diagnosing vasovagal syncope in patients with a history of
      typical vasovagal syncope.

PMID- 9141372
TI  - Controlled reperfusion after myocardial ischemia in a canine model monitored by
      two-dimensional phosphorus 31 chemical shift spectroscopic imaging.
AB  - Phosphorus 31 magnetic resonance spectroscopy at 2 T was used to monitor high
      energy phosphate metabolism over a 3-week period in a canine model of myocardial
      infarction and reperfusion. Twenty animals were divided into two groups: group 1
      (n = 11) received intravenous nitroglycerin beginning at the onset of coronary
      occlusion; group 2 (n = 9) received a 105-minute infusion of superoxide dismutase
      (SOD) beginning at the onset of reperfusion. A metabolic protective effect was
      observed (vs controls) with both agents, manifested by a reduction in the degree
      of pH decline from baseline values and preservation of the adenosine
      triphosphate/total phosphate ratio during occlusion and reperfusion. Further,
      both treatments, compared with controls, produced a lower infarct/zone at risk
      ratio: controls, 1.5 +/- 1.2; nitroglycerin, 0.52 +/- 0.50; and SOD, 0.64 +/-
      0.40. The technique of 31P magnetic resonance spectroscopy demonstrated its use
      for the noninvasive assessment of myocardial metabolism in response to
      therapeutic intervention.

PMID- 9141373
TI  - Causes of failed angioplasty for acute myocardial infarction assessed by
      intravascular ultrasound.
AB  - Coronary angioplasty is gaining increased importance as a primary treatment of
      acute myocardial infarction, but the complication rate of the procedure is higher
      than in stable coronary artery disease. In a consecutive series of 110 coronary
      angioplasties in patients with acute myocardial infarction, the cause of
      initially failed procedures was studied by intravascular ultrasound. The balloon
      angioplasty was immediately successful in 66%. In those cases with crossing of
      the lesion but a dissatisfying dilatation result (persistent occlusion,
      reocclusion, or dissection) an intravascular ultrasound probe could be advanced
      to 32 of 34 lesions. The information provided by ultrasound guided the subsequent
      bailout therapy. Persistent occlusions were caused by extensive thrombosis in
      4.5% of all cases, subsequently treated by local thrombolysis for 12 to 16 hours,
      and in 1.8% by a ruptured plaque, which was treated by stenting. In cases with
      Thrombolysis in Myocardial Infarction (TIMI) flow II, angiography suggested a
      thrombus in 9.1%, but intravascular ultrasound could detect dissections instead
      of a thrombus in half the cases. In cases of dissection, stenting was performed.
      Dissections were observed by angiography in 15.5%, and all cases were confirmed
      by ultrasound. In vessels >2.5 mm the dissection was treated by stenting.
      Overall, in 20 of 21 lesions stents were successfully implanted. No stent
      thrombosis was observed. With the assistance of intravascular ultrasound during
      bailout therapy, the success of coronary angioplasty to achieve TIMI flow III
      without residual stenosis in an unselected consecutive patient cohort with acute
      myocardial infarction was 96%. In direct angioplasty for acute myocardial
      infarction the procedure is frequently complicated by events such as plaque
      rupture and extensive vascular thrombosis, which are uncommon in coronary
      angioplasty for stable angina. Intravascular ultrasound provided insight into the
      underlying morphologic characteristics of failed angioplasty that enhanced the
      information provided by coronary angiography and assisted in the selection of the
      bailout therapy.

PMID- 9141374
TI  - Assessment of coronary artery aneurysms with multiplane transesophageal
      echocardiography.
AB  - Coronary artery aneurysms are rare and may be difficult to detect clinically.
      Multiplane transesophageal echocardiography provides numerous imaging planes that
      may improve the assessment of coronary aneurysms and act as an adjunct to
      standard angiography. Five patients with angiographically detected coronary
      aneurysms were studied with multiplane transesophageal echocardiography and
      Doppler flow imaging. Transesophageal echocardiography was successful in
      identifying the size and characteristics of the coronary aneurysms. Doppler
      ultrasound identified markedly increased flow velocity in a patient with a
      coronary arteriovenous fistula and decreased coronary flow velocity in two
      patients with aneurysmal coronary arteries and intracoronary thrombus. Multiplane
      transesophageal echocardiography is a useful, noninvasive method of assessing
      coronary artery aneurysms and may act as an adjunct to angiography in identifying
      fistula anastomosis.

PMID- 9141375
TI  - Correlation between plasma homocyst(e)ine and aortic atherosclerosis.
AB  - Plasma homocyst(e)ine [H(e)] levels correlate with the prevalence of arterial
      occlusive diseases. Recently, transesophageal echocardiography (TEE) has been
      used to evaluate patients with atherosclerotic plaques in the thoracic aorta. The
      purpose of this study was to determine whether H(e) levels correlate with the
      degree of atherosclerotic plaque in the thoracic aorta (ATH) as seen on TEE.
      Maximum plaque areas for three locations in the thoracic aorta (arch, proximal
      descending, and distal descending) were measured with TEE in 156 patients.
      Maximum plaque areas for these locations were added to yield an estimate of ATH.
      ATH and H(e) levels, and levels of folic acid, vitamin B12, and pyridoxal 5'
      phosphate were measured in a double-blind manner. Univariate analysis
      demonstrated a significant correlation of H(e) with ATH (r = 0.3, p< 0.001). On
      multivariate analysis, H(e) was independently predictive of ATH (r for the model
      including H(e) was 0.63, p < 0.0001). Plasma H(e) levels are therefore
      significantly and independently correlated with the degree of atherosclerosis in
      the thoracic aorta.

PMID- 9141376
TI  - Hemodynamic effects of fructose 1,6-diphosphate in patients with normal and
      impaired left ventricular function.
AB  - We compared the short-term hemodynamic effects of intravenous fructose 1,6
      diphosphate (FDP) administration in patients with coronary artery disease.
      Hemodynamic measurements were performed before and after administration of FDP in
      two groups of patients: those with impaired left ventricular (LV) function,
      elevated LV end-diastolic pressures (LVEDP > or =12 mm Hg, n = 30), and those
      with normal LV function (LVEDP <12 mm Hg, n = 17). In those with impaired LV
      function, FDP induced a decrease in LVEDP from 22 +/- 1.31 to 16.73 +/- 1.46 mm
      Hg (p< 0.0001). The cardiac index increased (2.50 +/- 0.11 to 2.81 +/- 0.13 L/m2
      [p < 0.0001]), as did the LV stroke work index (31.7 +/- 2.04 to 40.3 +/- 2.67 gm
      x m x m2 [p < 0.0001]). FDP induced no significant change in heart rate and mean
      aortic pressure. Pulmonary pressure and resistance declined (p<0.002 and p<
      0.0001, respectively). Systemic vascular resistance decreased because of
      increased cardiac output and unchanged arterial pressure (p < 0.001). In those
      patients with normal baseline LVEDP (5.06 +/- 0.27 mm Hg), FDP decreased heart
      rate (p< 0.0001) and systemic and pulmonary resistance (p < 0.03 and p < 0.004,
      respectively), whereas LVEDP and mean aortic and pulmonary pressures remained
      unchanged. FDP moderately increased cardiac output (p < 0.05), stroke volume
      index, and LV stroke work index (p< 0.002 and p< 0.003, respectively). The
      observed improvement in LV function in those patients with elevated LV filling
      pressures is thought to be a result of an increased energy production by the
      Embden-Meyerhoff pathway and to act as a positive inotrope.

PMID- 9141378
TI  - Aortic outflow obstruction in visceral heterotaxy: a study based on twenty
      postmortem cases.
AB  - Aortic outflow tract obstruction can complicate the clinical course and surgical
      management of patients with heterotaxy syndromes, but its anatomic basis has not
      been described in detail. In 20 postmortem cases with asplenia (n = 4) or
      polysplenia (n = 16), the anatomic causes of aortic outflow tract obstruction
      were absence of the subaortic conus in association with (1) narrowing of the
      subaortic outflow tract between the conal septum anteriorly and the common
      atrioventricular (AV) valve posteriorly in six (30%) patients; (2) aortic valvar
      atresia in four (25%), three with asplenia and one with polysplenia; (3)
      redundant AV valve leaflets in four (20%); (4) excessive AV valve fibrous tissue
      in four (20%); (5) marked hypoplasia of the mitral valve and left ventricle in
      two (10%); and (6) aneurysm of membranous septum in one (5%). One patient
      belonged to group (1) and (4). Aortic outflow tract obstruction was much more
      common with polysplenia (28%) than with asplenia (4%) (p < 0.001).

PMID- 9141377
TI  - Association of calcium channel blocker use with increased rate of acute
      myocardial infarction in patients with left ventricular dysfunction.
AB  - The Studies of Left Ventricular Dysfunction (SOLVD) assessed the effect of
      enalapril in patients with systolic left ventricular dysfunction (LVD). We
      performed retrospective analyses of the association between calcium channel
      blocker (CCB) use and fatal and nonfatal myocardial infarction (MI) in these
      patients. MI occurred in 11.5% of 845 patients receiving CCBs versus 7.5% of 2551
      patients not receiving CCBs in the enalapril group and in 14.4% of 874 patients
      receiving CCBs versus 9.3% of 2527 patients not receiving CCBs in the placebo
      group. By multivariate Cox regression analysis, adjusting for comorbidity, cause
      and severity of LVD, heart failure, and concomitant drug use, CCB use was an
      independent predictor of MI (relative risk [RR] 1.37, confidence interval [CI]
      1.14 to 1.63). The increase in MI risk was greater among patients with a higher
      heart rate (RR 1.46, CI 1.14 to 1.86) and lower blood pressure (RR 1.45, CI 1.14
      to 1.86). The adjusted risk ratio for all-cause mortality associated with CCB use
      was 1.14 (CI 1.00 to 1.28; p = 0.0454). In this analysis of patients with LVD,
      CCB use was associated with significantly increased risk of fatal or nonfatal MI.

PMID- 9141379
TI  - Possibility of postnatal left ventricular growth in selected infants with non
      apex-forming left ventricles.
AB  - To evaluate postnatal left ventricular growth potential, we reviewed the
      echocardiograms of seven infants with left ventricles that did not form an apex.
      Prostaglandins were used to maintain patency of the ductus arteriosus in six
      infants. Associated abnormalities included aortic stenosis in five, coarctation
      in three, and left atrial isomerism in one. Initial echocardiographic
      measurements (7 +/- 9 days) were compared with measurements at 1 month (36 +/- 9
      days). Weight (3.0 +/- 0.1 vs 3.0 +/- 0.5 kg) and body surface area (BSA) (0.2 +/
      0.01 vs 0.2 +/- 0.01 m2) did not change. Comparing initial measurements with
      measurements at 1 month, there were significant increases (p < 0.05) in aortic
      annulus diameter (4.5 +/- 0.5 vs 5.6 +/- 0.7 mm), aortic root diameter indexed to
      BSA (2.9 +/- 0.5 vs 3.7 +/- 0.7 cm/m2), ratio of the long axis of the left
      ventricle to the long axis of the heart (0.74 +/- 0.1 vs 0.86 +/- 0.1), left
      ventricular end-diastolic volume indexed to BSA (10 +/- 2 vs 24 +/- 9 ml/m2),
      left ventricular mass indexed to BSA (27 +/- 13 vs 47 +/- 28 gm/m2), mitral valve
      area indexed to BSA (2.3 +/- 0.5 vs 3.2 +/- 0.7 cm2/m2), left ventricular area
      (2.1 +/- 0.5 vs 3.6 +/- 1.1 cm2), and Rhodes score (-2.7 +/- 0.5 vs -1.1 +/-
      0.9). Tricuspid valve area indexed to BSA (5.8 +/- 1.5 vs 6.1 +/- 1.1 cm2/m2) and
      long axis of the heart indexed to BSA (13.0 +/- 2.8 vs 13.6 +/- 2.9 cm/m2) did
      not change. The increase in measurements appeared adequate for biventricular
      physiology in five infants (four are alive [3.9 +/- 2.6 years] and one died after
      not being able to wean from the ventilator). These data suggest that a non-apex
      forming left ventricle may have postnatal growth potential.

PMID- 9141380
TI  - Angiographic deterioration of target coronary artery narrowing as a result of
      percutaneous balloon angioplasty.
AB  - We evaluated the long-term angiographic outcome of balloon angioplasty by
      comparing original and follow-up target coronary narrowing. Rather than using
      restenosis to determine outcome, as in most angioplasty studies, we took an
      unusual approach and analyzed outcome in terms that are commonly used in
      progression and regression studies after medical interventions. Quantitative
      angiographic measurements were undertaken in 315 narrowings with an initial
      diameter stenosis <90% before and after angioplasty and at follow-up.
      Angiographic deterioration (>10% increase in follow-up diameter stenosis) was
      identified in 44 (14%) narrowings. Angiographic deterioration was not influenced
      by age, sex, risk factors, lipid profile, or the indication for angioplasty.
      Deterioration was also not predicted by the severity, length, or the location of
      the narrowing. The deteriorating narrowings had a higher recoil after dilatation
      compared with narrowings with angiographic improvement (21% +/- 31% vs 12% +/-
      17%, p = 0.006); the residual stenosis after angioplasty was therefore higher.
      The late loss was also significantly increased compared with narrowings with
      angiographic improvement (65% +/- 26% vs 8% +/- 24%, p < 0.001). We conclude that
      the incidence of angiographic deterioration of coronary disease as a result of
      restenosis is uncommon but not negligible. Interventional cardiologists should
      resist the temptation to dilate mild, silent coronary narrowings because the
      procedure might have an unfavorable angiographic (and probably clinical) effect.

PMID- 9141381
TI  - Long-term pacemaker dependency after radiofrequency ablation of the
      atrioventricular junction.
AB  - This prospective study was conducted to determine the percentage of patients with
      long-term pacemaker dependency after successful radiofrequency ablation of the
      atrioventricular junction. Abrupt inhibition of the pacemaker was performed 13.5
      +/- 8.1 months after ablation in 59 patients. A > or =5-second asystole was
      considered to indicate pacemaker dependency. Pacemaker dependency was present in
      18 patients. Absence of escape rhythm immediately after ablation was strongly
      associated with a higher incidence of long-term pacemaker dependency. The
      following variables were not associated with pacemaker dependency: age, presence
      of cardiac disease, presence of preablation bundle branch block, number of
      radiofrequency applications, a bilateral approach for ablation, and continuation
      of antiarrhythmic therapy after ablation. We concluded that (1) long-term
      pacemaker dependency is present in 30.5% of the patients after successful
      atrioventricular junction radiofrequency ablation and (2) absence of escape
      rhythm immediately after ablation predicts long-term pacemaker dependency.

PMID- 9141383
TI  - Detection of unsuspected myocardial necrosis by rapid bedside assay for cardiac
      troponin T.

PMID- 9141382
TI  - Decreased low-density lipoprotein oxidation after repeated selective apheresis in
      homozygous familial hypercholesterolemia.
AB  - Familial hypercholesterolemia was the first genetic disorder recognized to cause
      myocardial infarction. Patients with homozygous familial hypercholesterolemia
      have rapidly progressive coronary atherosclerosis with angina pectoris,
      myocardial infarction, or sudden death at a young age. Selective apheresis on
      dextran sulfate cellulose columns reduces mortality and may induce regression of
      coronary lesions. These patients have both increased levels and prolonged
      circulation residence time of low-density lipoprotein (LDL), which is not removed
      by cellular receptor. LDL oxidation may play a pivotal role in atherogenesis. LDL
      undergoes oxidation before being taken up by macrophages and then transformed
      into arterial wall foam cells. The aim of this study was to investigate LDL
      oxidation in eight homozygous patients with familial hypercholesterolemia during
      repeated LDL apheresis. LDL lipid peroxidation, estimated by conjugated-diene
      absorbance at 234 nm, lipid peroxides, and malondialdehyde showed an increased
      resistance against oxidation after repeated LDL apheresis. This phenomenon was
      also observed in the oxidative indexes of protein moiety of LDL (apolipoprotein
      B100 fragmentation, trinitrobenzenesulfonic acid reactivity, and electrophoresis
      agarose mobility). Similarly, cholesteryl esterification was decreased after LDL
      apheresis. Thus selective LDL apheresis not only decreases the pool of LDL, but
      it also induces changes that render LDL less susceptible to oxidation. This
      phenomenon might contribute to reduce coronary atherosclerosis and thus mortality
      of these particular patients.

PMID- 9141384
TI  - Dual left anterior descending coronary artery and anomalous aortic origin of the
      left circumflex coronary artery: a rare and complicated anomaly.

PMID- 9141385
TI  - Balloon occlusion delivery technique for closure of patent ductus arteriosus.

PMID- 9141386
TI  - Pacemaker-related endocarditis inducing tricuspid stenosis.

PMID- 9141387
TI  - Sequential development of fetal aortic valve stenosis and endocardial
      fibroelastosis during the second trimester of pregnancy.

PMID- 9141388
TI  - Max Goldstein and deaf education: a century of progress.

PMID- 9141390
TI  - Pass/fail rates for repeated click-evoked otoacoustic emission and auditory brain
      stem response screenings in newborns.
AB  - The click-evoked otoacoustic emission (EOAE) recording procedure is a simple and
      quick test to perform. Some suggest that the EOAE is a more efficient newborn
      hearing screening procedure than the auditory brain stem response (ABR). However,
      one shortcoming of the EOAE is a high false-positive rate in newborns, which is
      attributed to ear-canal debris. The purposes of this study were to assess the
      initial pass/fail rates of ABR and EOAE measurements and the effectiveness of
      repeated EOAE measurements as a method of reducing the false-positive rate. Fifty
      healthy, low-risk newborns sequentially underwent ABR, repeated EOAE, otoscopy,
      EOAE, and ABR if necessary. The initial ABR passing rate was 98%, whereas the
      EOAE passing rate was 61%. The EOAE passing rate improved with each retest and
      approximated the ABR rate by the fourth test. EOAE failures and the overall level
      of the EOAE were found to be significantly related to the amount of ear-canal
      debris. These results indicate that some newborns will require four or more tests
      before they eventually pass. Further study is needed to determine the overall
      cost-effectiveness of the EOAE as compared with the ABR before specific
      recommendations for a universal hearing screening program are proposed.

PMID- 9141389
TI  - A molecular, clinical, and immunohistochemical study of vestibular schwannoma.
AB  - The molecular pathogenesis of vestibular schwannoma has been investigated by
      determining the extent of chromosome 22 loss of heterozygosity in 77 tumors and
      relating these findings to clinical and immunohistochemical indexes of tumor
      behavior. Loss of heterozygosity was looked for at eight chromosome 22q loci.
      Clinical details were obtained in all 77 cases, and a clinical growth index was
      calculated for each tumor. The proliferative index was estimated in all tumors by
      using a monoclonal antibody to the proliferating cell nuclear antigen and by
      calculating the labeling index. Forty percent (31 of 77) of the tumors showed
      allele loss, and in each case this loss involved the region of the
      neurofibromatosis type 2 gene. No evidence was found that the presence of
      chromosome 22 allele loss was associated with the clinical growth index. On the
      log scale, however, an association was seen between the clinical growth index and
      the proliferating cell nuclear antigen labeling index p = 0.001). These results
      suggest that chromsome 22 allele loss is a frequent event in vestibular
      schwannoma. Tumor behavior, however, appears to be independent of the chromosome
      22 mutation. It is proposed that chromosome 22 allele loss and neurofibromatosis
      type 2 gene inactivation is an early event, possibly involved in the initiation
      of tumorigenesis in vestibular schwannoma. Tumor growth appears to be independent
      of this mutation and is likely to be determined by other as yet undefined
      factors.

PMID- 9141391
TI  - Anomalously coursing facial nerves above and below the oval window: three case
      reports.
AB  - Anomalous coursing of a dehiscent horizontal segment of the facial nerve,
      overlying or running below the oval window, is a rare phenomenon exclusively
      associated with conductive deafness caused by developmental abnormalities of the
      stapes and occasionally coincident with additional types of congenital auricular
      and nonauricular abnormalities. This article describes three new cases of this
      entity, including one previously unreported coincidence of an abnormally
      contracted tympanic ring, which should serve to alert the surgeon to the danger
      of surgical damage to a dehiscent, displaced facial nerve.

PMID- 9141392
TI  - Contemporary management of cerebrospinal fluid rhinorrhea.
AB  - Management of patients with cerebrospinal fluid rhinorrhea (CSF) remains
      controversial. Most studies recommend either an endoscopic or an external
      extracranial approach, depending on the surgeon's preference. Eighteen patients
      with CSF rhinorrhea have been managed at our institution since 1990. The causes
      of the CSF rhinorrhea consisted of functional endoscopic sinus surgery (7),
      lateral rhinotomy with excision of a benign nasal tumor (3), spontaneous
      rhinorrhea (7), and secondary repair after intranasal ethmoidectomy (1). In 11
      patients the CSF leak was recognized at the time of surgery; in 10 of these
      patients it was repaired during the primary surgery, whereas one patient
      underwent secondary repair after failure of conservative management of his CSF
      fistula. Seven patients underwent exploration for spontaneous CSF rhinorrhea.
      Four patients had computer tomography scans that showed the leak, and two
      patients had cisternography to localize the leak. One patient underwent magnetic
      resonance cisternography. Both of these leaks were identified with cisternography
      and were then confirmed intraoperatively. Repair methods included a pedicled
      septal mucosal flap (4), a free mucosal graft from the septum (7), and a middle
      turbinate (5). Two patients had obliteration of the sinus with muscle/fascia and
      fibrin glue. Eight patients were repaired endoscopically. The remainder underwent
      repair through external approaches. Seventeen patients (at a minimum 1 year
      follow-up) remain free from leakage. One patient required a second repair 8
      months after surgery. Iatrogenic trauma remains the most common cause of CSF
      rhinorrhea. Management at the initial setting is the least morbid approach and is
      successful in 95% of cases. Whether an endoscopic or external approach is used
      depends on surgical expertise and experience.

PMID- 9141393
TI  - Efficacy of ototopical ciprofloxacin in pediatric patients with otorrhea.
AB  - OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of
      topical ciprofloxacin in patients with recurrent otorrhea that was unresponsive
      to other antibiotics. METHODS: Pediatric patients with otorrhea and confirmed
      Pseudomonas aeruginosa in the ear fluid were enrolled. Topical ciprofloxacin,
      three drops three times daily for 14 days, was prescribed with aural care.
      Efficacy and safety were evaluated on days 7 and 14. A phone follow-up was
      conducted monthly thereafter for 8.6 months. RESULTS: Twenty-nine pediatric
      patients were enrolled. On day 14, 18 were cured, 8 were improved, 2 were changed
      to an alternate therapy and cured, and 1 showed no improvement, perhaps due to a
      small external ear canal. Two additional patients were cured at day 21. None of
      the patients reported any adverse effects. Twelve patients had no recurrence at 3
      to 15 months after the study. CONCLUSION: The use of topical ciprofloxacin in
      pediatric patients was curative in nearly 70% of patients with otorrhea
      associated with P. aeruginosa who were previously unresponsive to other
      antimicrobials. No adverse reactions were reported in the study population.

PMID- 9141394
TI  - A comparison of the biocompatibility of three absorbable hemostatic agents in the
      rat middle ear.
AB  - Absorbable gelatin sponge (Gelfoam) has been used for many years in middle ear
      surgery. Although the sponge is generally well tolerated, fibrosis occasionally
      forms in the mesotympanum; some studies indicated that the absorbable gelatin
      sponge may be responsible. Many of these studies lack statistical analysis. We
      prospectively studied three absorbable hemostatic agents in the middle ear of
      adult male Sprague-Dawley rats to determine which promotes fibrosis to the
      greatest degree: absorbable gelatin sponge (Gelfoam), absorbable gelatin sheet
      (Gelfilm), or absorbable collagen sheet (Instat). The materials were implanted in
      the middle ear through a post-auricular approach and the temporal bones were
      serially harvested at different time intervals so we could examine histologic
      changes. The nonimplanted ear served as surgical control. Examination of the
      specimens at 6, 8, and 10 weeks by light microscopy revealed that although
      absorbable gelatin film and collagen-absorbable hemostat are well tolerated in
      this animal model, absorbable gelatin sponge promoted the presence of fibrosis to
      a significantly greater degree, (p = 0.0344). We conclude that absorbable gelatin
      sponge promotes fibrosis more frequently than do collagen-absorbable hemostat and
      absorbable gelatin film in this animal model.

PMID- 9141395
TI  - Suppressive factor or factors derived from head and neck squamous cell carcinoma
      induce apoptosis in activated lymphocytes.
AB  - Our laboratory has previously identified a soluble factor derived from head and
      neck squamous cell carcinoma that impairs lymphocyte proliferative responses in
      vitro. This study further investigates the nature of the interaction between
      these factors and T lymphocytes. The proliferative activity of phytohemagglutinin
      stimulated peripheral blood lymphocytes and the Jurkat T-cell line was
      significantly suppressed (>50%) by the supernatants of 13 (41.9%) of 31 recently
      explanted head and neck squamous cell carcinoma samples. A characteristic
      morphologic appearance of these suppressed cells and ladderlike pattern of DNA
      fragmentation on gel electrophoresis indicated that the suppressive supernatants
      were inducing or predisposing T cells to apoptotic death. This apoptosis-inducing
      activity may be similar to that previously described in a suppressive supernatant
      obtained from an esophageal carcinoma cell line. These results shed further light
      on the mechanism behind a soluble immunosuppressive factor or factors produced by
      head and neck squamous cell carcinoma.

PMID- 9141396
TI  - Physiologic motion after laryngeal nerve reinnervation: a new method.
AB  - In this study a new method of reinnervation for unilateral recurrent laryngeal
      nerve paralysis was performed in canines, producing physiologic vocal fold motion
      in each of a small series of animals. During the procedure the left anterior
      division of the recurrent laryngeal nerve was reinnervated with axons from the
      thyroarytenoid branch of the contralateral recurrent laryngeal nerve. The
      posterior branch of the left recurrent laryngeal nerve was divided and sutured to
      the ansa cervicalis to maintain tone in the posterior cricoarytenoid muscle. In
      all four animals, the right distal vocalis stump was reinnervated with an ansa
      cervicalis nerve branch. After 3 months physiologic vocal fold motion and
      electromyographic activity could be demonstrated during mechanical stimulation of
      the supraglottis (adduction) and during tracheostomy obstruction (abduction).
      Acoustic data revealed improvement of jitter, shimmer, signal-to-noise ratio, and
      vocal efficiency in reinnervated animals compared with paralyzed canines before
      treatment, although the results lacked statistical significance. This approach to
      the rehabilitation of unilateral vocal fold paralysis is discussed.

PMID- 9141397
TI  - Factors that predict metastasis of papillary and follicular thyroid cancers in
      Taiwan.
AB  - The purpose of this study is to explore the relationship of postoperative
      thyroglobulin level and other clinical factors with tumor metastasis. Analysis of
      281 pathologic lesions verified patients with papillary and follicular thyroid
      cancer who received their primary treatment at Chang Gung Memorial Hospital.
      Clinical information-including postoperative thyroglobulin levels, age, sex,
      primary tumor size, clinical staging, surgical methods, surgical findings, chest
      x-ray findings, and 131I uptake-were stored in the computer. Actual survival rate
      and univariate and multivariate analyses of these factors with the relationship
      of distant metastases were undertaken. Twenty-three patients in this study died
      of distant metastases from the thyroid cancer. Of these patients, 30.4% were
      older than 60 years. In contrast only 8.5% of patients in the survival group were
      older than 60 years (p < 0.05 in chi2). All of the papillary thyroid cancer
      patients with distant metastases displayed thyroglobulin levels higher than 25
      ng/ml, but only 24% (41 of 173 cases) of those without distant metastases had
      thyroglobulin levels higher than 25 ng/ml. In 12 follicular thyroid cancer
      patients with distant metastases, 11 patients' serum thyroglobulin levels were
      higher than 25 ng/ml. In contrast, only 7 of 33 patients with follicular thyroid
      cancer without distant metastases displayed similar thyroglobulin levels.
      Univariate analysis revealed that age, postoperative thyroglobulin levels, chest
      x-ray findings, pathologic type, and tumor size are associated with distant
      metastases. One-month postoperative serum thyroglobulin level could be used as a
      prognostic factor for papillary and follicular thyroid cancer patients with
      distant metastases.

PMID- 9141399
TI  - Percutaneous endoscopic gastrostomy by head and neck surgeons.
AB  - The endoscopic placement of percutaneous gastrostomy tubes has been an accepted
      technique for several years but has traditionally been performed by
      gastroenterologists and general surgeons. Fluoroscopically guided tube placement
      is now performed by radiologists. Head and neck surgeons have been slow to adopt
      the responsibility for placing percutaneous gastrostomy tubes despite the fact
      that most are proficient in both rigid and flexible esophagoscopy and trained in
      the Seldinger technique. We report on 41 percutaneous endoscopic gastrostomies
      performed in 39 patients by the Head and Neck Service at Stanford Medical Center
      between July 1, 1992, and August 30, 1995. There were 28 (71.8%) male and 11
      (28.2%) female patients. Eleven (28.2%) procedures were performed in patients at
      the time of major head and neck resections. Another seven (17.9%) patients
      underwent percutaneous gastrostomy tube placement at the time of their initial
      staging panendoscopy before receiving chemotherapy and radiation. Fifteen (38.5%)
      procedures were performed for severe postsurgical dysphagia. Six (15.4%) patients
      had neurologic dysfunction, and this procedure was often performed in conjunction
      with tracheostomy. There were no major complications. Two patients had to undergo
      intraoperative tube replacement at 7 months and 18 months for chronic infection
      and tube damage, respectively. The only other complication was local irritation
      at the surgical site, which occurred in 2 (5.1%) patients. Our experience with
      percutaneous gastrostomy tube placement confirms that this is a procedure that
      can be safely performed by head and neck surgeons and should be part of
      otolaryngology-head and neck surgery training. The ability to provide
      comprehensive care of head and neck cancer patients as well as a means of
      supplemental feeding in conjunction with performing tracheostomy in
      neurologically impaired patients will no doubt improve the service that our
      specialty can provide.

PMID- 9141400
TI  - Platysma myocutaneous flap: use for intraoral reconstruction.
AB  - Twenty patients were treated for intraoral epidermoid carcinoma with a single
      stage reconstructive technique using a myocutaneous flap based on the platysma
      muscle. This flap carries on its distal tip a portion of isolated cervical skin
      to be used for intraoral replacement of the resected tissue. The superior
      vascular pedicle, the submental branch of the facial artery, was used. The
      platysma skin flap will survive if the blood supply from at least one region is
      preserved. In addition, it may be beneficial to include the external jugular
      and/or the communicating veins in the flap. Only three minor complications were
      seen and healed spontaneously. The flap has proved to be highly reliable and has
      significant benefits over many other techniques commonly used for head and neck
      reconstruction.

PMID- 9141401
TI  - Use of an Internet-based journal club.
AB  - The on-line journal club is a useful example of the educational advantages
      created by the combination of current Internet technology with traditional
      journal club methods.

PMID- 9141398
TI  - Cartilage viability with interpolated skin flaps: an experimental study.
AB  - Although composite cartilage grafts are often used in conjunction with a midline
      forehead flap to repair full-thickness nasal defects, the timing of pedicle
      division, which optimizes cartilage viability, has yet to be determined. A rabbit
      animal model was designed to investigate this question. The skin flap pedicle was
      divided at 0 days, 4 days, 3 weeks, 6 weeks, and 10 weeks in each of five groups
      of five animals. Although early pedicle division led to partial skin flap
      necrosis, the cartilage grafts tolerated this ischemic period better. Cartilage
      viability was approximately 70% and did not differ significantly between the five
      groups. It is concluded that a larger composite graft and better definition of
      the skin flap's critical period are needed to determine optimum timing for
      pedicle division in this animal model.

PMID- 9141402
TI  - Middle ear and auditory tube: middle ear clearance, gas exchange, and pressure
      regulation.

PMID- 9141403
TI  - Craniofacial manifestations of the amniotic band syndrome.

PMID- 9141404
TI  - Spindle cell variant of embryonal rhabdomyosarcoma.

PMID- 9141405
TI  - Resolution of primary spontaneous cerebrospinal fluid rhinorrhea after computed
      tomographic cisternography.

PMID- 9141406
TI  - Vestibular dysfunction due to cryptococcal meningitis.

PMID- 9141407
TI  - Sudden hearing loss in sickle cell disease: a case report.

PMID- 9141408
TI  - Pleomorphic rhabdomyosarcoma of the submandibular salivary gland.

PMID- 9141409
TI  - Idiopathic midline destructive disease involving the paranasal sinuses and middle
      ear.

PMID- 9141410
TI  - Closed rhinolalia as a symptom of pneumomediastinum after tonsillectomy: a case
      report and literature review.

PMID- 9141411
TI  - Primary atrophic rhinitis: a summary of four cases and review of the literature.

PMID- 9141412
TI  - McCune-Albright syndrome (polyostotic fibrous dysplasia) with intracranial
      frontoethmoid mucocele.

PMID- 9141413
TI  - Small cell carcinoma of the lung metastatic to the palatine tonsil.

PMID- 9141414
TI  - Palate perforation from cocaine abuse.

PMID- 9141415
TI  - Intermediate filament proteins of the liver: emerging disease association and
      functions.

PMID- 9141416
TI  - The Child-Pugh classification as a prognostic indicator for survival in primary
      sclerosing cholangitis.
AB  - Clinical decisions in primary sclerosing cholangitis (PSC) depend upon
      understanding its variable natural history. Several prognostic models for
      survival have been developed. We explored the Child-Pugh Classification (CPC) to
      determine if it predicts survival as well as a disease-specific model (DSM). We
      identified 208 PSC patients who satisfied established criteria. Prognostic
      variables were measured from the first visit. Kaplan-Meier survival estimates
      were obtained for CPC twice, once censoring observations at orthotopic liver
      transplantation and again considering orthotopic liver transplantation as a
      failure. A stepwise Cox proportional hazards-model was used to identify the
      factors associated with mortality. For 208 patients, the mean follow-up was 70
      months (SD + 55). Kaplan-Meier 7-year survivals for CPC A, B, and C were 89.8%,
      68%, and 24.9%, respectively (P < .001). The Cox model identified CPC and age as
      the most significant predictors of mortality. Adding the DSM risk score did not
      significantly improve the fit of the model (P = .75). The following were
      concluded: 1) CPC is a powerful predictor of survival in PSC; 2) DSM does not
      enhance the predictive ability of CPC; and 3) CPC may be used as an alternative
      to the DSM in research studies and clinical decision-making.

PMID- 9141417
TI  - APF/CBP, the small, amphipathic, anionic protein(s) in bile and gallstones,
      consists of lipid-binding and calcium-binding forms.
AB  - Two very similar small anionic, amphipathic proteins, a phospholipid-binding
      apoprotein (anionic polypeptide fraction [APF]) and a calcium-binding polypeptide
      (CBP), are found abundantly in bile and all types of gallstones. The often
      disparate properties among various preparations of APF/CBP could reflect
      different sources and separation procedures, leading to partly degraded and/or
      denatured protein and varied association of bile salts, lipids, bile pigments,
      and detergents. The present study presents new methods for isolation and
      purification of APF/CBP, and characterizes the preparations thus obtained. It was
      found that isolation by selective precipitation of proteins from fresh T-tube
      bile by added calcium chloride, followed by demineralization with
      ethylenediaminetetraacetic acid (EDTA), removal of salts, lipids, and some
      pigment by Sephadex LH-20, and serial ultrafiltration yields the purest
      preparations. Though free of lipids, bile salts, detergents, and most pigments,
      these new preparations all show the same 7-kd and 12-kd bands on sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), the same major peaks on
      hydrophobic high-performance liquid chromatography (HPLC), and retain the self
      associative, lipid- and calcium-binding functions, typical of older preparations
      obtained by potentially denaturative procedures. The varied properties among
      APF/CBP preparations are thus apparently related mainly to their content of
      different proportions of two major components, lipid-binding APF and calcium
      binding CBP. Immunologic cross-reactions indicate common epitopes, and amino acid
      analyses are also similar, suggesting that APF and CBP may have the same
      polypeptide backbone, but differ because of posttranslational modification(s).
      Sufficiently pure APF and CBP have now been obtained to permit possible
      structural identification by sequencing and molecular biological techniques,
      though such attempts have thus far been unsuccessful.

PMID- 9141418
TI  - Histopathologic analysis of transjugular intrahepatic portosystemic shunts.
AB  - This prospective study was undertaken in 17 patients treated with 22 transjugular
      intrahepatic portosystemic shunt (TIPS) procedures and aimed to evaluate the
      nature and causes of short- and long-term shunt abnormalities. Specimens were
      collected after autopsy in 6 patients and after liver transplantation in 11
      patients; the time from shunting ranging from 4 to 385 days. During the first 2
      weeks the shunt surface was covered by poorly organized fibrin platelet clots
      that were mixed with inflammatory and red blood cells. Thereafter, a pseudointima
      developed, initially made of loose granulation tissue that was formed by edema,
      myofibroblasts, neo-capillaries, collagen fibers, and inflammatory cells. This
      pseudo-intima extended with time as the myofibroblasts increased in number, as
      the collagen fibers thickened, and as the inflammatory cells grew more scarce.
      Its thickness ranged from 50 to 3,500 microm, the maximal values being observed
      in the middle of the shunt. The shunt was obstructed by a clot in 4 patients
      (18%). In 7 shunts (31.8%) the pseudo-intima was thicker than 1,000 microm and
      was referred to as hyperplastic pseudo-intima. It showed more dense inflammatory
      infiltrate and anarchic deposition of more scarce collagen fibers. Pseudo-intima
      hyperplasia was associated with previously diagnosed thrombosis, which had been
      treated by dilatation in 2 cases and by biliary deposits in 3 cases, while it
      remained unexplained in 2 cases. Accordingly, this study confirms the following:
      1) that early TIPS obstruction results from thrombosis; 2) that 2 weeks after
      insertion, the stent is covered by a smooth pseudo-intima; 3) that thereafter,
      pseudo-intimal hyperplasia is the main cause of TIPS stenosis or occlusion; and
      4) that biliary secretions and previous thrombosis could be important triggering
      mechanisms for this pseudo-intima overgrowth.

PMID- 9141419
TI  - Clonotypic analysis of T cells in patients with autoimmune and viral hepatitis.
AB  - The immunopathogenesis of autoimmune hepatitis (AIH), and the role of T cells in
      the onset and maintenance of this disease, are still unclear. Since T cells
      expand clonally after stimulation by an antigen, it is important to analyze the
      behavior of T cells at a clonal level. We have established recently a novel
      system, using reverse transcriptase-polymerase chain reaction (RT-PCR) and
      subsequent single-strand conformation polymorphism (SSCP) that allows the
      identification of clonal accumulation of T cells in a lymphocyte population.
      Using this system, we demonstrated that oligoclonal T cells were accumulated in
      the liver of patients with AIH, and that identical T-cell clonotypes were
      detected in two different regions of the liver, although these features were also
      observed in cases with viral hepatitis. Only in cases with AIH, however, nearly
      all identical T cells were found to belong to CD8+ subset and there were very few
      CD4+ T cells in this population. Our results suggest that common antigens
      presented to CD8+ T cells in the context of HLA class I molecule are distributed
      diffusely in the liver of AIH. These findings also suggest that antigens
      recognized by CD4+ T cells may be relatively heterogeneous in the liver with AIH.

PMID- 9141420
TI  - Nuclear DNA fragmentation and expression of Bcl-2 in primary biliary cirrhosis.
AB  - It is uncertain whether or not apoptosis is involved in the pathogenesis of
      primary biliary cirrhosis (PBC). The aims of this study were to assess the
      nuclear DNA fragmentation and expression of Bcl-2 in the biliary epithelial cells
      (BECs) and in the hepatocytes of PBC. Additionally, the effects of
      ursodeoxycholic acid (UDCA) on DNA fragmentation and Bcl-2 expression in PBC were
      evaluated. Liver tissue specimens from 35 PBC patients were examined by in situ
      nick-end labeling to detect any nuclear DNA fragments, and by
      immunohistochemistry for Bcl-2. Ten of these patients underwent a second liver
      biopsy after the treatment with UDCA. Sixteen histologically normal liver tissues
      and 17 chronic viral hepatitis C (CVHC) samples were chosen as controls. DNA
      fragmentation in BECs was more frequently found in PBC than in CVHC and more
      frequently than in the normal controls (both P < .05), and fragmentation in the
      hepatocytes of PBC more frequently than in normal controls (P < .01). Bcl-2
      expression was more frequently found in both the BECs and hepatocytes of PBC than
      in the controls. UDCA significantly decreased the DNA fragmentation in BECs (P <
      .05) and the positivity for Bcl-2 in BECs (P < .01), although no significant
      decrease was found in hepatocytes. In conclusion, de novo Bcl-2 expression in
      hepatocytes of PBC was shown, and the increased nuclear DNA fragmentation and the
      Bcl-2 expression both in BECs and in hepatocytes may reflect apoptotic stress,
      although nuclear DNA fragmentation in BECs did not necessarily represent
      apoptosis. UDCA showed a potential effect of reducing nuclear DNA fragmentation
      in BECs.

PMID- 9141421
TI  - Comparative studies of antimitochondrial autoantibodies in sera and bile in
      primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by
      destruction of intrahepatic bile ducts. Although the pathogenesis of this disease
      is still unknown, high titers of antimitochondrial autoantibodies (AMA) have long
      been recognized in patient sera. However, little is known about the presence of
      AMA in bile. In this study, we investigated bile and sera from patients with PBC
      and healthy controls for the presence of AMA and mitochondrial autoantigens. AMA
      were detected in the bile of 17 of 19 patients (89.4%) with PBC; they were
      specifically directed against the pyruvate dehydrogenase complex (PDC-E2) in 15
      of 19 patients (78.9%), to the branched-chain 2-oxo-acid dehydrogenase complex E2
      (BCOADC-E2) in 6 of 19 patients (31.6%), and to the 2-oxoglutarate dehydrogenase
      complex E2 (OGDC-E2) in 1 of 19 patients (5.3%). In a comparative study of sera
      from the same patients, anti-PDC-E2 antibodies were found in 19 of 19 patients
      (100%), anti-BCOADC in 9 of 19 patients (47.3%), and anti-OGDC-E2 in 4 of 19
      patients (21.1%) patients. AMA in bile were always found together with antibodies
      of corresponding specificities in the serum from the same patient. Immunoglobulin
      (Ig)A AMA were found in the bile of 9 of 19 patients (47.7%) with PBC; they were
      specifically directed against PDC-E2 in 8 of 19 patients (42.1%) and to BCOADC in
      2 of 19 patients (10.5%). Epitope mapping of IgA anti-PDC-E2 antibodies indicated
      that, like serum autoantibodies, the immunodominant epitope is directed against
      the inner lipoyl domain of PDC-E2. The prevalence and antigen reactivity of IgA
      AMA in sera correlated completely with IgA AMA in bile. Autoantibodies against
      nuclear envelope pore proteins (gp210) were found in 1 of 8 (12.5%) sera of
      patients with PBC, but not in bile. Furthermore, and of particular interest, we
      detected the autoantigens, PDC-E2, OGDC-E2, and BCOADC-E2, in the bile of 12 of
      19 patients (63.2%), 9 of 19 patients (47.4%), and 9 of 19 patients (47.4%),
      respectively; PDC-E2 was found in only 1 of 17 (5.9%) disease controls. Although
      the presence of AMA in bile may merely reflect the presence of these antibodies
      in sera, the simultaneous detection of mitochondrial autoantigens in bile
      suggests an increase of mitochondrial autoantigens at inflammatory sites. Such
      autoantigens, coupled with AMA, may augment the local immune response and disease
      progression.

PMID- 9141422
TI  - Comparison of the clinical features and clinical course of antimitochondrial
      antibody-positive and -negative primary biliary cirrhosis.
AB  - Reports from North America and Northern Europe have suggested that
      antimitochondrial antibody (AMA) negative primary biliary cirrhosis (PBC) is a
      distinct chronic cholestatic liver disease with high prevalence of serum non
      organ-specific autoantibodies other than AMA. To evaluate if such a peculiar
      serum immunoreactivity is associated with clinically relevant characteristics, we
      reviewed our experience with 297 Italian patients who have had a clinical and
      histological diagnosis of PBC and were regularly followed-up at our Center from
      June 1974 to June 1994. AMA-negative and AMA-positive patients were compared in
      terms of biochemical and clinical features, and clinical outcome of the disease.
      At presentation, 30 of 297 patients (10%) tested negative for AMA by indirect
      immunofluorescence. Six of them tested positive for antimitochondrial M2
      antibodies (AMA-M2) by immunoblotting analysis, therefore, diagnosis of AMA
      negative PBC was made in 24 patients (8%). At the initial visit, AMA-negative and
      AMA-positive patients were similar in terms of biochemical and clinical features.
      Antinuclear and anti-smooth-muscle antibodies (ANA and ASMA) were more frequently
      positive in the AMA-negative patients (71% vs. 31%, and 37% vs. 9%; both P =
      .0002). Incidence of complications of cirrhosis and development of liver failure
      resulting in death or referral for liver transplantation did not differ
      significantly between the two populations. In conclusion, data from this
      historical cohort study suggest that the distinct serological features of AMA
      negative PBC are not associated with substantial differences in the clinical
      spectrum or course of the disease.

PMID- 9141423
TI  - Decreased natural killer cytotoxic activity in chronic alcoholism is associated
      with alcohol liver disease but not active ethanol consumption.
AB  - Chronic alcohol intake is associated with an increased incidence of certain
      neoplasms. Natural killer (NK) cells have been considered to be involved in
      control tumor development and growth. The goal of the present study was to
      contribute to a better understanding of the effects of ethanol (EtOH) per se on
      the NK-cell population. Both patients with chronic alcoholism without liver
      disease (AWLD) and subjects with alcohol-induced cirrhosis (ALC) were carefully
      selected for this study. Immunophenotypical and functional studies of peripheral
      blood (PB) NK-cells were performed during active EtOH intake and after 3 months
      of a withdrawal period. In the AWLD group a significant increase in number of NK
      cells (CD3-/CD56+) (P < .05) associated with a parallel increase in NK-cell lytic
      activity (P < .01) was observed. In addition, the number of cytotoxic T cells
      displaying the CD3+/CD56+ phenotype as well as CD8-/CD57+ NK-cell subset was also
      increased (P < .01 and P < .001, respectively). By contrast, in ALC patients with
      active EtOH intake (ALCET group), although a significant increase in the number
      of NK PB lymphocytes was observed (P < .05), NK lytic activity was depressed (P <
      .05), suggesting the existence of a decreased lytic activity/NK-cell. After 3
      months of EtOH withdrawal, PB mononuclear cells (PBMC) from the AWLD group
      patients still displayed an increased NK cytolytic activity; in addition, the
      number of PB NK-cells (CD3-/CD56+ and CD8-/CD57+) and CD3+/CD56+ PB T cells
      continued to be increased. Independently of the duration of withdrawal period, in
      ALC patients EtOH withdrawal was followed by a slight decrease in the NK lytic
      activity of PBMC with respect to the values in active alcoholism phase; slight
      differences observed in the NK lytic activity in ALC patients who quit drinking
      could be related to the tendency to decrease of the number of NK-cells toward
      normal values. Furthermore, although an increase in NK cytotoxic activity after
      stimulation of PBMC with interleukin-2 (IL-2) was observed in ALC, it did not
      reach the levels observed in healthy subjects. Overall, our results show that the
      behavior of PB NK-cell population in chronic alcoholism is different according to
      both the moment of EtOH consumption and the existence or not of ALC. Alcohol by
      itself induced an increase in the number and lytic activity of NK-cells. By
      contrast, the NK cytolytic activity is constantly depressed in the stage of
      alcoholic cirrhosis, supporting the notion that immunosurveillance mechanisms may
      be affected in these patients.

PMID- 9141424
TI  - Emergency banding ligation versus sclerotherapy for the control of active
      bleeding from esophageal varices.
AB  - Active bleeding varices are a great challenge to endoscopists. In this study, we
      compared the short-term efficacy and safety of banding ligation with injection
      sclerotherapy in the arresting of active bleeding from esophageal varices.
      Seventy-one cirrhotic patients with active variceal bleeding were randomized to
      receive banding ligation (37 patients) or sclerotherapy (34 patients) immediately
      after endoscopic examinations. Primary success rate (bleeding stopped for 72
      hours) was 97% in the ligation group and 76% in the sclerotherapy group (P =
      .009). The efficacy of ligation was similar to sclerotherapy in the control of
      oozing varices (100% vs. 89%, P = .23), whereas ligation was superior to
      sclerotherapy in the control of spurting varices (94% vs. 62%, P = .012). The
      requirement of vasoconstrictors after emergency endoscopic treatment was lower in
      the ligation group than in the sclerotherapy group (11% vs. 41%, P = .007).
      Treatment failure within 1 month was 8% in the ligation group vs. 30% in the
      sclerotherapy group (P = .02). Blood transfusion requirements were significantly
      lower in the ligation group than in the sclerotherapy group (3.2 +/- 1.2 vs. 4.5
      +/- 1.8 units, P < .01). Rebleeding rate within 1 month was 17% in the ligation
      group and 33% in the sclerotherapy group (P = .19). Significant complications
      were encountered in 5% of the ligation group and 29% of the sclerotherapy group
      (P = .007). Mortality rates within 1 month were 19% in the ligation group and 35%
      in the sclerotherapy group (P = .19). Banding ligation and sclerotherapy were
      comparable in the arresting of oozing varices, whereas ligation was superior to
      sclerotherapy in the control of spurting varices. Patients treated with ligation
      required fewer vasoconstrictors and fewer transfusion units than patients treated
      with sclerotherapy. Furthermore, banding ligation was associated with a lower
      complication rate than sclerotherapy.

PMID- 9141425
TI  - Anti-neutrophil cytoplasmic antibodies in type 1 and 2 autoimmune hepatitis.
AB  - Perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) have been recently
      defined as the most sensitive autoantibody of type 1 autoimmune hepatitis (AIH
      1). Their prevalence in type 2 autoimmune hepatitis (AIH-2) has not yet been
      evaluated. The aim of the present study was to verify the association of pANCA
      with AIH-1 in an Italian series and to investigate the prevalence of the
      antibodies in AIH-2 and in proper control groups represented by cases of chronic
      hepatitis C (CH-C) with similar autoimmune features. pANCA were found in 30 of 46
      (65%) AIH-1 and in 4 of 30 (13%) ANA/smooth muscle antibody (SMA) positive CH-C
      (P = .0000006). Nineteen AIH-2, 29 liver kidney microsomal antibody type 1/liver
      cytosol antibody type 1 (LKM1/LC1) positive CH-C cases and 50 healthy controls
      were all negative. In AIH-1, pANCA were significantly (P = .009) more frequent in
      males (8 of 9, 89%) than in females (22 of 37, 59%). All pANCA positive sera
      showed SMA of the antiactin type. The present data confirm that pANCA, although
      less prevalent in our series than in other reports, do associate with AIH-1 also
      in the Mediterranean area and show that it can identify a small subgroup (13%) of
      ANA/SMA positive chronic hepatitis C, in which autoimmune reactions might play a
      more relevant role than viral infection. They also show the antibodies are absent
      in AIH-2. In conclusion, pANCA appear to be mutually exclusive of LKM1
      positivity, either hepatitis C virus-related or not, thus representing a further
      valuable tool to differentiate the two types of autoimmune hepatitis.

PMID- 9141426
TI  - Expression of costimulatory molecules B7-1 (CD80) and B7-2 (CD86) on human
      hepatocellular carcinoma.
AB  - Costimulation mediated by costimulatory molecules, such as B7-1 and B7-2, which
      are ligands for the CD28/cytolytic T lymphocyte associated antigen (CTLA)-4
      counter-receptor, plays an important role in the induction of T cell-mediated
      antitumor immunity. We investigated the expressions of B7-1, B7-2, and human
      leukocyte antigen (HLA) class I in seven human hepatocellular carcinoma (HCC)
      cell lines by reverse transcription-polymerase chain reaction (RT-PCR) and flow
      cytometric analysis. RT-PCR showed that all these human HCC cell lines were
      positive for B7-1 and B7-2 at the messenger RNA (mRNA) level. Flow cytometric
      analysis revealed that they all expressed B7-1, B7-2, and HLA class I on the cell
      surface. However, the expression levels of B7-1 and B7-2 were very low whereas
      those of HLA class I were high. B7-1 and B7-2 expression could be increased by
      treatment with interferon alpha and interferon gamma in a dose-dependent manner,
      although the expression levels of B7-1 and B7-2 after interferon treatment
      remained low. By transfecting Hep3B cells with a plasmid containing human B7-1
      complementary cDNA (cDNA), we were able to establish Hep3B cell lines strongly
      expressing B7-1. From mixed lymphocytes and tumor cultures analysis, the primary
      cytolytic activity against parental Hep3B cells could be induced effectively by
      B71-transfected Hep3B cells. These findings suggested that B7-1 gene transfer is
      the best way to induce strong expression of this molecule and this might be
      useful for immuno-gene therapy against human HCC.

PMID- 9141427
TI  - Expression of alpha-fetoprotein and stem cell factor/c-kit system in bile duct
      ligated young rats.
AB  - The existence of a facultative hepatic stem cell compartment in bile ductules
      that participates in the renewal process of epithelial cell populations in the
      liver is well documented. The present study was undertaken to determine whether
      the immature bile epithelium responds differently to growth stimulus induced by
      bile stasis to that seen in the adult animal. In addition, the possible
      involvement of the growth factor/receptor systems associated with early
      activation of hepatic stem cells in bile duct proliferation was also examined.
      Bile duct ligation was used to induce the proliferation of bile epithelial cells.
      The expression of full-length alpha-fetoprotein (AFP) was used as an indicator
      for activation of the stem cell compartment. AFP was highly and selectively
      expressed in small bile ducts 7 days after bile duct ligation in immature rats up
      to 5 weeks of age. Although no significant increase in the expression of stem
      cell factor (SCF) c-kit, hepatocyte growth factor (HGF), and transforming growth
      factor-alpha (TGF-alpha) was observed 7 days after bile duct ligation in adult
      rats, the expression of all these growth factors was increased in bile duct
      ligated rats up to 5 weeks of age. These results suggest that the bile ductular
      epithelium in the young rats responds to bile stasis in a fashion that is
      phenotypically similar to that seen during early activation of hepatic stem cells
      in adult liver.

PMID- 9141428
TI  - The effect of changes in hepatocyte membrane potential on immediate-early proto
      oncogene expression following partial hepatectomy in rats.
AB  - The stimulus responsible for inducing hepatocytes to enter the cell cycle
      following partial hepatectomy (PHx) remains to be identified. One suggested
      candidate is the change in hepatocyte membrane potential (PD) that occurs
      immediately following PHx. To test this possibility, we monitored changes in
      hepatocyte PD and immediate-early proto-oncogene expression in rats pretreated
      with saline or gamma aminobutyric acid (GABA), an amino-acid neurotransmitter
      that hyperpolarizes isolated hepatocytes. Intraperitoneal injections of saline or
      GABA (500 microg/g body weight) were administered to adult, male Sprague-Dawley
      rats 1 hour prior to 70% PHx. Rats were sacrificed and the livers excised at
      various times until 180 minutes post-PHx for messenger RNA (mRNA) and protein
      analyses. In additional groups of saline- and GABA-treated rats, PD changes were
      recorded continuously from -260 to 180 minutes post-PHx. Serum GABA
      concentrations were determined by ion-exchange chromatography with
      orthopthaldehyde fluorescence detection. Hepatocyte PD's were recorded in situ by
      intracellular microelectrodes with an Axoprobe-1A amplifier. Steady-state levels
      of c-fos, c-jun, jun-B, and c-myc transcripts and proteins were documented by
      Northern blots of poly(A)-enriched RNA derived from resected livers and Western
      blots of total nuclear protein, respectively. Serum GABA concentrations remained
      unchanged in saline-treated controls but increased 10- to 20-fold above baseline
      values in GABA-treated rats. In saline-treated controls, hepatocyte
      depolarization occurred immediately and was maintained throughout the 180 minutes
      post-PHx period (PD pre-PHx, -36.8 +/- 5.1; 15 minutes post-PHx, -27.5 +/- 5.7;
      and 180 minutes post-PHx, -28.3 +/- 4.4 mV, mean +/- SD); whereas in GABA-treated
      rats, hepatocyte PD remained unchanged (-37.0 +/- 1.1; -36.4 +/- 3.1 and -39.2 +/
      2.7 mV, respectively). Despite abrogation of hepatocyte PD changes, proto
      oncogene mRNA and protein levels in saline- and GABA-treated rats were either
      similar or, in the case of c-fos and c-jun, increased five- to sevenfold in GABA
      treated rats. The results of this study indicate the following: 1) hepatocytes
      depolarize immediately post-PHx and remain depolarized throughout the priming
      phase of the cell cycle; 2) elevated serum GABA concentrations prevent PHx
      induced hepatocyte depolarization; and 3) depolarization is not the stimulus
      responsible for priming hepatocytes into replicative competence.

PMID- 9141429
TI  - Reperfusion after liver transplantation in rats differentially activates the
      mitogen-activated protein kinases.
AB  - The injury resulting from cold ischemia and warm reperfusion during liver
      transplantation is a major clinical problem that limits graft success. Kupffer
      cell activation plays a pivotal role in reperfusion injury, and Kupffer cell
      products, including free radicals and tumor necrosis factor alpha (TNF-alpha),
      are implicated as damaging agents. However, the second messengers and signaling
      pathways that are activated by the stress of hepatic ischemia/reperfusion remain
      unknown. The purpose of this study is to assess the activation of the three known
      vertebrate mitogen activated protein kinase (MAPKs) and the activating protein 1
      (AP-1) transcription factor in response to ischemia and reperfusion in the
      transplanted rat liver. There was a potent, sustained induction of c-jun N
      terminal kinase (JNK), but not of the related MAPKs extracellular signal
      regulated kinases (ERK) or p38, upon reperfusion after transplantation. TNF-alpha
      messenger RNA (mRNA) levels and transcription factors AP-1 and nuclear factor
      kappaB (NF-kappaB) were induced in the liver after 60 minutes of reperfusion.
      Finally, there was an elevation of ceramide, but not diacylglycerol or
      sphingosine, in the transplanted liver. Ceramide is a second messenger generated
      by TNF-alpha treatment and is an activator of JNK. Because JNK activation
      preceded the elevations in ceramide and TNF-alpha mRNA, these results suggest
      that increased hepatic TNF-alpha and ceramide may perpetuate JNK induction, but
      that they are not the initiating signals of JNK activation during reperfusion
      injury in the transplanted liver.

PMID- 9141430
TI  - Pretreatment with activated protein C or active human urinary thrombomodulin
      attenuates the production of cytokine-induced neutrophil chemoattractant
      following ischemia/reperfusion in rat liver.
AB  - We investigated the role of anticoagulant in the ischemia/reperfusion injury of
      the liver, using activated protein C (APC), active human urinary thrombomodulin
      (UTM), and factor Xa blocked at the active site (DEGR-Xa). Liver ischemia was
      induced in male Wistar rats by occlusion of the portal vein with a microvascular
      clip for 30 minutes. Each anticoagulant was injected intravenously 10 minutes
      before clamping the portal vein. Serum concentrations of cytokine-induced
      neutrophil chemoattractant (CINC) were determined by enzyme-linked immunosorbent
      assay. The serum levels of CINC increased significantly following reperfusion,
      reaching a peak in 6 hours, and then decreasing gradually to control levels by 24
      hours. CINC levels in rats pretreated with APC (500 U/kg), UTM (3,000 TMU/kg), or
      DEGR-Xa (10 mg/kg) peaked 3 hours following reperfusion and decreased rapidly to
      baseline level within 6 and 12 hours, respectively. These peak values were
      significantly lower than those observed in untreated rats (P < .01). Expression
      of CINC transcripts in liver tissue of untreated rats was evaluated by Northern
      blot analysis and peaked 3 hours following reperfusion. Pretreatment with these
      anticoagulants significantly decreased the expression of CINC messenger RNA
      transcripts as compared with untreated animals. Myeloperoxidase activity and the
      number of neutrophils accumulated into the liver 24 hours following
      ischemia/reperfusion were also significantly decreased in animals pretreated with
      these anticoagulants. In addition, correlations between the peak values of liver
      enzymes and serum CINC levels were found to be significant (P < .001). The
      inactive derivative of factor Xa, a selective inhibitor of thrombin generation,
      inhibited ischemia/reperfusion-induced increases in the serum concentration and
      messenger RNA transcript quantities of CINC. The inactive factor Xa also reduced
      hepatic accumulation of neutrophils after ischemia/reperfusion. These results
      indicate that the release of CINC is likely related to the hepatic
      microcirculation disturbance induced by microthrombotic occlusion following
      ischemia/reperfusion.

PMID- 9141431
TI  - Urinary transforming growth factor beta1 levels in hepatitis C virus-related
      chronic liver disease: correlation between high levels and severity of disease.
AB  - To assess the clinical relevance of transforming growth factor beta1 (TGF-beta1)
      in chronic liver disease, urinary TGF-beta1 and circulating aminoterminal
      propeptides of type III procollagen (PIIINP) levels were determined by
      radioimmunoassay in 100 cirrhotic patients, 44 patients with chronic hepatitis,
      and 50 healthy controls. TGF-beta1 and PIIINP levels in cirrhotic patients were
      higher than those in patients with chronic hepatitis (each P < .0001) or healthy
      controls (each P < .0001), respectively. There was a correlation between TGF
      beta1 and PIIINP levels in patients (r = .858, P < .0001). The higher the urinary
      TGF-beta1 level, the worse the severity of chronic liver disease (P < .001). TGF
      beta1 levels in cirrhotic patients with antibodies to hepatitis C virus (anti
      HCV) were higher than in those without (P < .0001). Compared with cirrhotic
      patients with hepatitis B surface antigen (HBsAg) alone, those with HBsAg and
      anti-HCV had higher TGF-beta1 levels (P < .001), a higher frequency of raised TGF
      beta1 (P < .005), and a higher frequency of patients with Child-Pugh C (P <
      .005). Multivariate analysis indicated that the TGF-beta1 level was significantly
      correlated with the presence of cirrhosis. In conclusion, urinary TGF-beta1
      levels may be used as a marker for hepatic fibrogenesis. Higher urinary TGF-beta1
      levels correlate with more severe liver disease.

PMID- 9141432
TI  - Heat shock protein induction in murine liver after acute treatment with cocaine.
AB  - The effect of cocaine on heat shock protein (hsp) induction in murine liver was
      examined using Western blotting and immunohistochemistry. A single dose of
      cocaine (50 mg/kg, intraperitoneal [i.p.]) was administered to naive,
      phenobarbital (PB)-induced or beta-naphthoflavone (betaNF)-induced mice, and the
      level of hsps in the liver analyzed 3, 6, and 24 hours after the cocaine dose. As
      measured by Western blotting, hsp70i levels were increased at all time points,
      and hsp25 levels at the 6- and 24-hour time points. Levels of hsp60, hsc70, and
      hsp90 remained unchanged. Pretreatment of mice with the cytochrome P-450
      inhibitor SKF-525A eliminated both cocaine hepatotoxicity and the induced
      accumulation of hsp25 and hsp70i. Immunohistochemical localization of hsp25 and
      hsp70i in the liver showed that concentrations of both hsps were elevated only in
      cells with altered morphology. As has been observed previously, hepatic enzyme
      induction with PB or betaNF shifted the location of the necrotic lesion within
      the lobule from zone 2, as observed in naive mice of this strain, toward zone 1
      (PB) or zone 3 (betaNF), respectively. Localization of induced accumulation of
      hsp25 and hsp70i was found to shift within the lobule in parallel with the
      necrotic lesion in these animals. Immunostaining of cocaine reactive metabolites
      bound to proteins was superimposable on the areas with hsp accumulation and cells
      with altered morphology. Our observations indicate a strong spatial correlation
      within the lobule between cocaine reactive metabolite formation, induced
      accumulation of hsp25 and hsp70i, and cytotoxicity (necrosis).

PMID- 9141433
TI  - Ectopic expression of the calcium-binding protein parvalbumin in mouse liver
      endothelial cells.
AB  - To elucidate the physiological role of the Ca2+ binding protein parvalbumin, we
      have generated transgenic mice carrying the full-length complementary DNA (cDNA)
      of rat parvalbumin under the control of the heavy-metal inducible metallothionein
      IIA promoter. Immunohistochemical and biochemical methods have been used to
      detect the presence of ectopic parvalbumin expression in different tissues. Here
      we show the expression of parvalbumin in endothelial cells lining the liver
      sinusoids in situ and after isolation in vitro. The hemodynamic effects of
      endothelin 1, a peptide hormone mediating potent vasoconstriction via calcium
      signalling, were investigated in the mouse liver perfused in situ.
      Vasoconstriction, thought to be mediated by the Ito cell, was not affected in the
      transgenic animals, whereas microvascular exchange, probed with the multiple
      indicator dilution technique, was markedly decreased in normal mice but virtually
      not affected in the transgenic animals. This suggests that ectopically expressed
      parvalbumin is involved in the regulation of Ca2+ signals in the sinusoidal
      endothelial cells. This animal model could be of interest to those working on the
      physiology of liver circulation.

PMID- 9141434
TI  - Pancreatic secretory trypsin inhibitor as a diagnostic marker for adult-onset
      type II citrullinemia.
AB  - Adult-onset type II citrullinemia is characterized by which deficiency of
      argininosuccinate synthetase (ASS) protein is found specifically in the liver of
      patients. Our recent study using differential messenger RNA (mRNA) display showed
      that the expression of human pancreatic secretory trypsin inhibitor (hPSTI) mRNA
      increases significantly in the liver of all type II patients tested. In the
      present work, we found that the concentration of hPSTI protein was higher in the
      liver of type II patients than controls. Because it is well known that PSTI is a
      secretory protein and because serum PSTI has been proposed as a marker of
      pancreatic and nonpancreatic diseases, we measured the hPSTI level in the blood
      of type II patients and compared it with other serum markers such as elastase 1,
      trypsin, phospholipase A2, alpha-fetoprotein, CA19-9, and C-reactive protein
      (CRP). We found a significant increase in serum hPSTI level with no change in the
      other serum markers. These results suggest that serum hPSTI is useful as a
      diagnostic marker for adult-onset type II citrullinemia.

PMID- 9141435
TI  - Effect of cell density and epidermal growth factor on the inducible expression of
      CYP3A and CYP1A genes in human hepatocytes in primary culture.
AB  - The influence of cell density and epidermal growth factor (EGF) on the expression
      and inducibility of cytochrome P450 (CYP) genes of the CYP3A and CYP1A families
      in adult human hepatocytes in primary culture has been evaluated. Only when
      cultured at subconfluence and in the presence of EGF did hepatocytes exhibit a
      proliferative response, assessed by measuring DNA synthesis and cyclin A
      accumulation. In the absence of EGF, the accumulation of CYP3A4 and CYP1A2
      messenger RNAs (mRNAs) in response to their respective inducers (rifampicin and
      dioxin) was dramatically decreased in subconfluent culture with respect to
      confluent cultures. The presence of EGF only slightly decreased the accumulation
      of these mRNAs in both confluent and subconfluent cultures. The accumulation of
      CYP2D6 and CYP2E1 proteins, which are constitutively expressed in confluent
      cultures, and the production of fibrinogen and apolipoprotein (Apo) B100
      exhibited similar behavior, while nicotinamide adenine dinucleotide phosphate
      cytochrome c reductase activity was affected neither by cell density nor by EGF.
      In contrast, the accumulation of CYP1A1 mRNA in response to dioxin was similar in
      confluent and subconfluent cultures, irrespective of the presence of EGF.
      Interestingly, CYP3A7, a gene that is preferentially expressed in the fetal
      liver, was expressed constitutively neither in confluent nor in subconfluent
      cultures, irrespective of the presence of EGF. It is concluded that the loss of
      cell-cell contacts rather than the proliferative status of cells per se is
      responsible for the dramatic decrease in the expression of CYP genes, normally
      expressed in the adult human liver.

PMID- 9141436
TI  - Hepatic basolateral sodium-dependent-bile acid transporter expression in two
      unusual cases of hypercholanemia and in extrahepatic biliary atresia.
AB  - The recent cloning of a human sodium-dependent bile acid transporter (NTCP)
      permits analysis of its expression in human liver disease and investigation of
      potential primary defects in its expression. NTCP from normal human liver (NHL)
      was first characterized in detail. Northern blotting of RNA from NHL revealed a
      1.8-kb NTCP transcript. Western blotting of crude NHL plasma membranes using a
      carboxyterminal antipeptide antibody showed that NTCP is a 39-kd polypeptide that
      is N-glycosylated to a final molecular weight of 56 kd. Indirect
      immunofluorescent analysis of NHL sections indicated that the NTCP protein is
      expressed on the basolateral surface of hepatocytes. We hypothesized that the
      clinical phenotype of a defect in NTCP might be hypercholanemia in the relative
      absence of liver disease. Accordingly, the coding region of the NTCP gene of two
      children with this phenotype was sequenced after reverse transcription/polymerase
      chain reaction (RT/PCR) amplification. No primary defects in the deduced NTCP
      amino acid sequence were found. Despite the extremely high serum bile salt levels
      (235 and 126 micromol/L) in these two patients, NTCP messenger RNA (mRNA) and
      protein expression were quantitatively normal, in contrast to the published
      observations in a rat model of cholestasis secondary to common bile duct
      ligation. Hepatic steady-state NTCP mRNA levels in a group of 23 pre- and
      postportoenterostomy biliary atresia patients were inversely related to total
      bilirubin, indicating that extrahepatic bile duct obstruction leads to down
      regulation of NTCP mRNA levels, similar to that observed in rat common bile duct
      ligation. Therefore the lack of down-regulation in the two patients with
      hypercholanemia indicates that elevated serum bile salts are not sufficient to
      down-regulate NTCP expression, these two patients have abnormal responses to
      hypercholanemia, or these two patients have a defect in a gene other than NTCP
      that influences hepatic clearance of bile salts.

PMID- 9141438
TI  - Cell lines with heterogeneous phenotypes result from a single isolation of
      albumin-sv40 T-antigen transgenic rat hepatocytes.
AB  - Several immortalized cell lines were established from the livers of two
      transgenic rats expressing the simian virus protein large T antigen under the
      control of the albumin promoter. Hepatocytes from transgenic rats were isolated
      by a two-step perfusion procedure from a normal-appearing liver and from a liver
      that contained a single neoplasm. Cells were also isolated from the dissociated
      liver neoplasm. After 5 weeks in culture, cell colonies were isolated and
      subcloned as individual cell lines. Electron microscopy revealed that all cell
      lines had a high nuclear-to-cytoplasmic ratio compared with normal hepatocytes.
      The cytoplasm contained numerous organelles, including smooth and rough
      endoplasmic reticulum, Golgi, mitochondria, peroxisomes, and annulate lamellae.
      However, the lines exhibited a variety of different cell morphologies. All cell
      lines, including those derived from neoplastic cells, exhibited a similar
      doubling time of 26 hours and the ability to grow in soft agar. Northern blot
      analysis revealed that the cell lines differentially expressed hepatocyte
      markers. Large T antigen was expressed in the cultured cell lines at much higher
      levels than was observed in transgenic hepatocytes in vivo. This suggests that
      the viral protein is required to maintain cell viability in culture. In addition,
      the tumor suppressor proteins, p53 and Rbp105, were detected in all cultured cell
      lines. In contrast, these same proteins were not detected by Western blot in
      transgenic hepatocytes in vivo. All cell lines expressed the oncogene c-myc, yet
      growth factor-dependent and independent growth were observed. The data presented
      show for the first time the establishment and characterization of a number of
      cell lines derived from hepatocytes isolated from an alb-SV40 large T-antigen
      transgenic rat. These cell lines exhibited varied morphological and biochemical
      hepatocellular characteristics in vitro, suggesting that the expression of the
      transgene in hepatocytes leads to considerable phenotypic diversity analogous to
      that seen in hepatocellular carcinomas induced by chemical carcinogenesis.

PMID- 9141437
TI  - Endotoxin impairs biliary glutathione and HCO3- excretion and blocks the
      choleretic effect of nitric oxide in rat liver.
AB  - Cholestasis in patients with sepsis has been attributed to the effects of
      endotoxin (lipopolysaccharides, LPS) and LPS-induced cytokines, which are also
      potent stimulators of systemic and hepatic nitric oxide (NO) synthesis. NO donors
      stimulate bile acid-independent bile flow in normal rat liver, but the effects of
      LPS-induced NO on bile formation remain unclear. To address this question we
      examined the effects of NO and its mediator guanosine 3',5'-cyclic monophosphate
      (cGMP) on bile flow and biliary HCO3- and glutathione excretion in isolated
      perfused rat livers (IPRL) from LPS-treated rats. Portal and systemic NO2- + NO3-
      plasma levels were increased 47-fold in LPS-treated rats and were also elevated
      in perfusate (6-fold) and bile (9-fold) after isolating and perfusing livers from
      these animals. Bile flow, HCO3-, and glutathione output were decreased by 33%,
      25%, and 81% in these IPRL, respectively. Stimulation of NO synthesis with L
      arginine or inhibition of inducible NO synthesis with aminoguanidine did not
      change bile flow, although pretreatment with aminoguanidine inhibited NO
      production by 85%. Moreover, the choleretic effects of infusions of the NO donors
      sodium nitroprusside (SNP) and S-nitroso-acetyl-penicillamine were markedly
      reduced in endotoxemic IPRL compared with normal controls, and SNP-induced HCO3-
      and glutathione excretion were reduced by 61% and 86%, respectively. SNP-induced
      cyclic GMP production was 2.3-fold lower than in normals, but the choleretic
      effect of dibutyryl cGMP was only slightly reduced in endotoxemic livers. These
      findings indicate that LPS reduces bile acid-independent bile flow primarily by
      inhibiting biliary excretion of glutathione and to a lesser extent HCO3-, whereas
      LPS-induced NO does not modulate bile formation in endotoxemia. Thus, impairment
      of the major determinants of bile acid-independent bile flow by LPS may
      contribute significantly to the pathogenesis of the cholestasis of sepsis.

PMID- 9141439
TI  - The expression of endosomal rab proteins correlates with endocytic rate in rat
      liver cells.
AB  - Hepatic endocytosis is characterized by a division of labor between the different
      cell types with respect to endocytosis, which is mediated by receptors expressed
      on their cell surface. We have investigated the expression of GTPases of the rab
      family in rat liver parenchymal and endothelial cells. Small GTPases of the rab
      protein family control distinct steps of intracellular transport both in the
      secretory and the endocytic pathway. As controls have been employed the normal
      rat kidney (NRK) cell line and brain tissue, neuronal cells are known to express
      high levels of components of the endocytic machinery (clathrin, adaptins,
      dynamin, uncoating adenosine triphosphatase, etc.). Endothelial cells were found
      to express four to seven times more rab4, rab5, and rab7 than parenchymal cells.
      A similar relationship was found between the endocytic rates in the two cell
      types; the rate of internalization from the plasma membrane of mannose receptors
      in rat liver endothelial cells was 2.3 pools/min, whereas the corresponding value
      for internalization of the galactose receptor in parenchymal liver cell was 0.27
      pools/min (comparable with the rate of transferrin internalization in NRK cells).
      Both immunofluorescence and subcellular fractionation experiments showed that
      rab5 and rab7 were associated with compartments along the endocytic pathway.
      Brain tissue showed a similar high expression of endocytic components (rab4,
      rab5, and rab7) as liver endothelial cells, whereas lower values were found in
      NRK cells. We also analyzed the following proteins involved in endocytosis:
      clathrin, alpha-adaptin, beta-adaptin, and rabaptin-5. These proteins showed the
      same pattern of expression as the rab proteins. In conclusion, the results
      obtained with liver cells corroborate the data obtained in transfected cells and
      support the notion that rab proteins may be involved in controlling the endocytic
      rate in liver cells.

PMID- 9141440
TI  - Hrp12, a novel heat-responsive, tissue-specific, phosphorylated protein isolated
      from mouse liver.
AB  - Previous studies from this laboratory identified a 28-kd nonreducible protein,
      liver-derived immunoinhibitory factor (LDIF) from the mouse liver. Isolation of
      this protein resulted in the co-purification of another unique protein called
      heat responsive protein 12 kd (Hrp12). In contrast to LDIF, Hrp12 was totally
      reducible to a protein of 12 kd suggesting a dimer. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) purification, followed by
      sequencing of an in situ cyanogen bromide digest of membrane bound Hrp12, yielded
      an internal 20-amino acid polypeptide. Degenerate oligonucleotides made from this
      peptide were used to screen a murine liver complementary DNA (cDNA) library. A
      1240-bp cDNA clone was obtained with an internal 521-bp open reading frame (ORF).
      Sequence analysis of the 173-amino acid ORF of mouse Hrp12 showed a high degree
      of homology with a 99 amino acid rat liver-kidney perchloric acid-soluble protein
      (LKPS) and a 136-amino acid perchloric acid soluble rat protein (PSP).
      Transcripts for Hrp12 were mainly restricted to the liver and kidney in mouse and
      man. The protein was estimated to be approximately 0.8% of the total liver
      soluble cytosolic protein. A zoo-blot probed at moderate stringency with labeled
      cDNA revealed a strong conservation of the gene in all of the mammalian species
      tested. Analysis of the protein structure of Hrp12 revealed motifs predicted to
      be targets for protein kinase C (PKC). More importantly, purified mouse Hrp12
      could be phosphorylated in vitro with PKC. The protein had significant similarity
      to DnaK heat shock protein (Hsp)70 and contained a 54-amino acid stretch with
      sequence similarity to Hsp90. This prompted us to investigate the heat shock
      response of Hrp12. Isolated hepatocytes and hepatoma cells were exposed to
      different heat shock temperatures (39.5 degrees C, 42.5 degrees C, and 44.5
      degrees C); and then total RNA was extracted and Northern analysis carried out.
      The message for this novel protein responded atypically to heat shock. Although
      the steady-state level of the message increased after heat shock, a marked
      oscillatory pattern was superimposed on it. In contrast, the steady-state levels
      of Hsp90 and Hsp70 messenger RNA (mRNA) were found to respond to heat shock in
      the expected manner. Finally, the amount of Hrp12 protein was also found to
      increase after heat shock in a manner that was consistent with heat-responsive
      proteins.

PMID- 9141441
TI  - Alcohol use after liver transplantation in alcoholics: a clinical cohort follow
      up study.
AB  - The purposes of this study were to determine among a cohort of long-term
      alcoholic survivors after liver transplantation (1) the incidence of alcohol use,
      (2) its effect on allograft integrity and extrahepatic health, and (3) the
      validity of the pretransplant alcohol prognosis screening process. Retrospective
      clinical cohort study of all alcoholic patients undergoing orthotopic liver
      transplantation at a single center from February 1987 until January 1991 with
      follow-up through December 1994, giving a median duration of follow-up of 63
      months (range, 6-89 months). Multidisciplinary liver transplantation program at a
      tertiary-care academic medical center. Fifty alcoholic, long-term liver
      transplant recipients. The frequency of alcohol relapse, defined as any alcohol
      use in the period after transplantation, was determined by two questionnaire
      studies and by clinical follow-up. Allograft integrity was assessed by coded
      review of serial percutaneous allograft biopsies. Potential systemic effects of
      alcohol relapse were assessed by chart review. The alcohol prognosis screening
      process was evaluated by retrospectively comparing pretransplant estimates of
      putative indicators of alcoholism prognosis in posttransplant alcohol users and
      abstainers. Thirty-three recipients (66%) consistently denied any alcohol use
      throughout the duration of posttransplant follow-up, whereas 17 (34%) were
      identified as having consumed alcohol at least once since the transplant. There
      were no significant differences at the time of evaluation between abstainers and
      alcohol users in age, sex distribution, severity of liver dysfunction, median
      duration of abstinence, or University of Michigan alcoholism prognosis score. The
      median interval from transplantation to alcohol relapse was 17 months, with a
      range of 3 to 45 months. Recurrent alcohol use was associated with significant
      medical complications sufficient to require admission to the hospital in 6
      patients. One patient died of graft dysfunction, noncompliance with
      immunosuppressant medications, and presumed graft rejection while drinking. Mild
      or progressive hepatitis, which was the most common abnormality in posttransplant
      liver biopsy findings, was equally distributed between both alcohol users and
      abstainers and sometimes occurred in the absence of antibody to hepatitis C virus
      antibodies. There was a similar frequency of biopsy-proven acute cellular
      rejection in alcohol users and abstainers. Typical histological features of
      alcoholic liver injury were present in posttransplant biopsies from 1 alcohol
      user only. Alcohol use by alcoholics is uncommon in the first 5 years after liver
      transplantation, and alcohol-associated liver injury is unusual. Mild nonspecific
      hepatitis is common in both alcohol users and nonusers alike. Among a small
      subset of alcoholic transplant recipients, drinking behavior after liver
      transplantation is associated with considerable morbidity, requiring hospital
      admissions and occasionally leading to graft loss and death.

PMID- 9141442
TI  - Resolution of gas exchange abnormalities and intrapulmonary shunting following
      liver transplantation.
AB  - This prospective study evaluated pulmonary gas exchange in patients with severe
      liver disease, its relationship to intrapulmonary shunting, and its response to
      liver transplantation. Detailed clinical examinations, chest radiographs, and
      arterial blood gas estimations were performed on 74 consecutive patients before
      and after liver transplantation. Fifty percent of the 74 patients had a widened
      alveolar-arterial (A-a) oxygen gradient (> 15 mm Hg) and 45% a reduced PaCO2 (<
      35 mm Hg). Twenty-two percent were hypoxemic (PaO2 < 80 mm Hg). Following
      transplantation mean PaO2 increased (pre-89 +/- 14 vs. post-94 +/- 8 mm Hg; P =
      .014) and A-a oxygen gradient decreased (pre-16 +/- 14 vs. post-8 +/- 9 mm Hg; P
      < .001), despite an increase in PaCO2 (pre-36 +/- 5 vs. post-39 +/- 4; P < .001).
      To examine this improvement in oxygen exchange further, a subgroup of 26
      consecutive patients, with no obvious cardiorespiratory cause for abnormal gas
      exchange underwent, pre- and post-operative spirometry, measurement of carbon
      monoxide diffusion capacity (DLCO), intrapulmonary shunt estimations (100% oxygen
      technique), and echocardiography. In this subgroup, 23% were hypoxemic, 54% had a
      widened A-a oxygen gradient, and 85% had increased intrapulmonary shunting (> 5%)
      before transplantation. There was a significant correlation between the degree of
      pre-transplantation intrapulmonary shunting and A-a oxygen gradient (P < .01).
      Nineteen of the 22 patients with increased shunting improved following
      transplantation and improved A-a oxygen gradient correlated well with the
      reduction in shunting (P < .005). DLCO was reduced in 69% of these patients with
      a mean value of 73% of predicted. However, the post-transplantation mean DLCO did
      not increase despite the improvement in oxygen exchange. In conclusion, gas
      exchange abnormalities are common in patients with severe liver disease but these
      usually resolve post-transplantation. Intrapulmonary shunting is a major
      determinant of abnormal oxygen uptake in transplant candidates without evidence
      of cardiorespiratory disease. Finally, the mechanism for the reduced DLCO is
      unclear but appears different to that responsible for intrapulmonary shunting and
      abnormal oxygen exchange.

PMID- 9141443
TI  - Peripheral blood chimerism following human liver transplantation.
AB  - The aim of this study was to prospectively investigate the peak levels and
      kinetics of donor leucocyte chimerism in human recipients following liver
      transplantation. The peak levels of chimerism were observed within the first 48
      hours following transplantation and ranged from 0.15% to 20% of total peripheral
      blood mononuclear cells. In all but one patient, who developed graft versus host
      disease, there was an early peak level of chimerism that declined over time such
      that donor leukocytes were only intermittently detectable after 3 to 4 weeks. In
      8 patients who had no episodes of graft rejection, the peak level of donor
      leukocyte chimerism ranged from 1.3% to 20% (mean +/- SEM; 5.5% +/- 2.1%). In 3
      patients who were treated for episodes of acute graft rejection during the first
      four postoperative weeks, the peak level of donor leukocyte chimerism ranged from
      0.15% to 0.2% (0.18 +/- 0.02, P = .012). The results demonstrate a marked
      variation in the total number of donor leukocytes detectable in the peripheral
      blood early after liver transplantation and also, that lower levels of chimerism
      may be associated with lower rates of initial graft acceptance and a higher
      incidence of acute rejection.

PMID- 9141444
TI  - Hepatitis C virus-related proteins in kidney tissue from hepatitis C virus
      infected patients with cryoglobulinemic membranoproliferative glomerulonephritis.
AB  - Membranoproliferative glomerulonephritis (MPGN) may be a component of a
      generalized vasculitis as well as a component of the clinical expression of type
      II mixed cryoglobulinemia (MC). Several studies have established a striking
      association between hepatitis C virus (HCV) infection and MC. The potential role
      of HCV in the pathogenesis of MPGN, which occurs in almost half of the cases of
      MC patients, has not been fully investigated, and the demonstration of HCV
      proteins as the antigenic constituent of the glomerular immune deposits has
      remained elusive. Kidney biopsy specimens were obtained from 12 HCV RNA, antibody
      to HCV (anti-HCV)-positive patients with MPGN and type-II MC, and from 8 controls
      (3 HCV RNA, anti-HCV-negative patients with MPGN and MC and 5 with
      noncryoglobulinemic "idiopathic" MPGN). Murine monoclonal antibodies developed
      against c22-3, E2/NS1, c33c, c100-3, and NS5 proteins were used to detect HCV
      related antigens by indirect immunohistochemistry. Acid electroelution of tissue
      sections was performed to enhance the sensitivity of the immunohistochemical
      method. Specific HCV-related proteins were detected in glomerular and tubulo
      interstitial vascular structures in 8 (66.7%) HCV-positive MC patients and in
      none of the HCV RNA, anti-HCV-negative controls. HCV immunoreactive deposits
      displayed the following two major patterns: 1) a linear, homogeneous deposition
      along glomerular capillary walls, including endothelial cells and sub-endothelial
      spaces; and 2) a granular bead-like appearance with distinct deposits in
      mesangial and paramesangial cells. Immunoglobulin G (IgG) and M (IgM) and C3
      fraction deposition in adjacent kidney sections displayed features comparable
      with those found for HCV deposits. Patients with granular deposits showed more
      pronounced renal impairment and severe proteinuria. These findings indicate that
      in MC patients with HCV-associated MPGN, kidney deposits consist of HCV
      containing immune complexes that are likely to play a direct pathogenetic role in
      the renal damage.

PMID- 9141445
TI  - Early antibody response against hypervariable region 1 is associated with acute
      self-limiting infections of hepatitis C virus.
AB  - Antibodies directed to hypervariable region 1 (HVR1) of hepatitis C virus (HCV)
      have recently been shown to neutralize the corresponding HCV isolate in vitro. We
      analyzed the appearance of antibodies directed to HVR1 during the course of
      infection in a large group of patients who have been infected by the same isolate
      of a HCV contaminated anti-D immunoglobulin (HCV-AD78). An enzyme-linked
      immunosorbent assay (ELISA) was established using a synthetic peptide to detect
      antibodies against the main HVR1 variant of HCV-AD78. 207 sera obtained at
      different time points post infection (p.i.) of 51 patients having either acute
      self-limiting (n = 28) or chronic infection (n = 23) were studied. Antibodies
      directed to HVR1 were found at least at one time point during the infection
      course in 15 of 28 patients (53%) having acute self-limiting infections and in 17
      of 23 patients (74%) with chronic disease. The time of appearance of anti-HVR1
      was significantly different between these two patient groups (P < .025) although
      appearance and titers of other HCV-specific antibodies were found to be similar
      at early time points p.i. In acute self-limiting infections 9 of 21 sera (43%) of
      respective patients with sera available within the first 6 months p.i. were anti
      HVR1 positive. The highest prevalence of anti-HVR1 in this group of patients was
      within month 6 to 12 p.i. (64%). None of the sera available after 24 months p.i.
      had such antibodies. In contrast, only 2 of 15 sera (13%) of chronically infected
      patients with respective time points of sera were anti-HVR1 positive within the
      first 6 months p.i. and only 5 of 18 sera (28%) were positive within month 7 to
      12 p.i. Seven patients with chronic HCV infections showed at least two
      consecutive anti-HVR1 negative early time points up to month 18 p.i. Prevalence
      of anti-HVR1 after 24 months p.i. was high (84%) in this group of patients and
      most of the patients maintained high levels of anti-HVR1 for up to 17 years p.i.
      Our findings suggest clearance of virus by respective neutralizing antibodies
      resulting in a self-limiting infection and may have implications for prognosis of
      the disease and also for any future vaccine development.

PMID- 9141446
TI  - Hepatitis C virus genome complexity correlates with response to interferon
      therapy: a study in French patients with chronic hepatitis C.
AB  - Recent studies performed in Japan have suggested that hepatitis C virus (HCV)
      genome heterogeneity might be taken as a predictive virological parameter of
      response to interferon alfa (IFN-alpha) treatment. However, there is presently no
      information on the impact of this virological parameter in patients from Western
      countries infected by different HCV genotypes. We have investigated this issue by
      using amplification of HCV E2 hypervariable region 1, followed by single-strand
      conformation polymorphism assay (PCR-SSCP). We have studied 95 French patients
      infected with various genotypes and treated with IFN-alpha-2b. We analyzed the
      impact of the following parameters by univariate and multivariate analyses: HCV
      heterogeneity, HCV genotype, viral load, and liver histology in response to
      therapy. Age >40 years (P < .01), viral load >35 x 10(5) Eq/mL (P < .01),
      genotype 1 (P < .01), and a number of SSCP bands >3 (P < .001) were significantly
      associated with nonresponse or relapse; cirrhosis was associated with
      nonresponse. In multivariate analysis, three variables were independently
      associated with the absence of long-term response: SSCP bands >3, genotype 1, and
      viral load >35 x 10(5) with odds ratios of 19, 7.5, and 11.8, respectively. Our
      data establish the major importance of HCV genome heterogeneity in patients
      infected with both HCV types associated with low (genotype 1b) or high (genotype
      3a) response to IFN-alpha.

PMID- 9141447
TI  - Association of seropositivity for hepatitis viruses and aplastic anemia in
      Thailand.
AB  - Aplastic anemia is more common in the Orient than in western countries, with an
      incidence in Thailand that is 2- to 3-fold higher than in Europe. Aplastic anemia
      after hepatitis is a well characterized clinical entity, and clinical hepatitis
      is also prevalent in the Far East. We performed a prospective case-control study
      to determine risk factors for aplastic anemia in Bangkok and two rural regions
      during 1989 to 1994. A total of 375 cases were identified, along with 1,174
      hospital controls matched for age and sex. Historical data were collected by
      trained interviewers. Sera from a subset of cases (N = 177) and controls (N =
      183) were tested for antibodies to hepatitis viruses A, B, and C and hepatitis B
      surface antigen. There was no evidence of association of aplastic anemia with
      hepatitis B or hepatitis C. Previous exposure to hepatitis A, as determined by
      immunoglobulin G (IgG) seropositivity, was significantly associated with aplastic
      anemia: the relative risk adjusted for confounding was 2.9 (95% confidence
      interval 1.2-6.7). The same association also existed for persons under age 25
      years, in whom the prevalence of hepatitis A IgG was lower than in the total
      population. However, no patients showed evidence of recent infection with
      hepatitis A (immunoglobulin M [IgM] seropositivity). These results indicate that
      exposure to a hepatitis virus is a risk indicator for aplastic anemia in
      Thailand, and while itself unlikely to be etiologic, hepatitis A may be a
      surrogate marker for another enteric microbial agent.

PMID- 9141448
TI  - Detection of hepatitis GB virus type C RNA in serum and liver from children with
      chronic viral hepatitis B and C.
AB  - The aim of this work was to study the presence of the hepatitis GB virus type C
      (HGBV-C) in liver and serum samples of children with chronic viral hepatitis, the
      time course of changes in viral RNA, and the possible acquisition routes of
      infection. Frozen serum and liver samples from 58 children with chronic hepatitis
      B (n = 33) or C (n = 25) were analyzed using polymerase chain reaction. Twenty
      seven children had been included in different interferon trials. Two additional
      serum samples from the HGBV-C-positive children as well as serum samples from 29
      of their relatives were also analyzed. HGBV-C RNA was detected in serum and liver
      samples from 9 of 58 (15%) of children as well as in serum samples from 3 of 29
      of the relatives of the HGBV-C-infected children: the mother and the brother of
      one child (index case A) and the mother of another child (index case B). The
      homologies of the HGBV-C RNA sequences were 93% between index case A and his
      mother, 88% between index case A and his brother, and 94% between index case B
      and his mother. In the 3 children receiving alpha-interferon, HGBV-C RNA became
      undetectable during treatment although it reappeared in 2 of them after therapy.
      In conclusion, we found that 15% of children with chronic viral hepatitis were
      coinfected with HGBV-C. HGBV-C RNA was simultaneously present in serum and liver
      samples and tended to remain detectable even after alpha-interferon therapy. Our
      results suggest that vertical transmission of HGBV-C may occur.

PMID- 9141449
TI  - Detection of GBV-C RNA in patients with non-A-E fulminant hepatitis by reverse
      transcription polymerase chain reaction.
AB  - GBV-C might be a causative agent of fulminant hepatitis of unknown etiology.
      Fulminant hepatitis is an indication for liver transplantation. However, in
      Japan, because of the legal difficulties associated with cadaveric donation,
      patients with fulminant hepatitis are still treated by plasmapheresis and
      multiple transfusions of fresh frozen plasma. So, the possibility that GBV-C
      might be transmitted by transfusions after the onset of fulminant hepatitis is
      real. Therefore, we have examined the possible role of GBV-C in non-A-E fulminant
      hepatitis. Nine patients with non-A-E fulminant hepatitis and one with non-A-E
      late onset hepatic failure were examined. Sera were obtained from the patients at
      admission before any blood or blood products were given, and again after
      transfusions. GBV-C RNA was detected by nested reverse transcription polymerase
      chain reaction with primers based on the reported sequence. GBV-C RNA was
      negative in all 10 pretransfusion patients with non-A-E fulminant hepatitis or
      late onset hepatic failure. Then, fresh frozen plasma was transfused to these
      patients, and four of them became seropositive. GBV-C is unlikely to be a major
      etiologic agent for non-A-E fulminant hepatitis in Japan.

PMID- 9141450
TI  - Hepatitis G virus in patients with cryptogenic liver disease undergoing liver
      transplantation.
AB  - To examine the prevalence of hepatitis G virus (HGV) in end-stage liver disease
      of unknown cause and the role of HGV infection in posttransplantation hepatitis,
      we studied 46 patients undergoing liver transplantation (mean age, 50 years; M:F,
      18:28) with cryptogenic cirrhosis. HGV RNA was detected by polymerase chain
      reaction (PCR) and was quantified by a branched DNA (bDNA) assay. The prevalence
      of HGV RNA was determined in samples collected before and after liver
      transplantation and was found to be 22% and 67%, respectively. We evaluated the
      prevalence of posttransplantation hepatitis in 25 patients, 16 of whom were HGV
      positive and 9 were HGV-negative. The proportion of patients with hepatitis was
      not significantly different in the two groups (38% in HGV-positive and 22% in HGV
      negative patients). The median histological scores were significantly higher in
      liver biopsies from patients with HGV infection than in those without HGV
      infection (2 [range, 0-14] and 1 [range, 0-3]; P = .01), but the histological
      scores were low overall. The duration of follow-up was similar in the two groups.
      HGV RNA levels were not correlated with the severity of liver disease based on
      histological score (r = -.08). Graft survival and patient survival were not
      significantly different. We concluded that liver disease was frequent (32%) after
      transplantation in patients with a pretransplantation diagnosis of cryptogenic
      cirrhosis, although the disease was generally mild. Although HGV RNA was
      demonstrable in the majority (67%) of patients after transplantation, there was
      no relationship between the presence of HGV RNA and the presence of
      posttransplantation liver disease. The finding of posttransplantation hepatitis
      in the absence of known viruses (A-G), suggests that other, as-yet-unidentified
      viruses may be important.

PMID- 9141451
TI  - Hepatitis G virus co-infection in liver transplantation recipients with chronic
      hepatitis C and nonviral chronic liver disease.
AB  - Hepatitis G virus (HGV) is a newly described RNA virus that is parenterally
      transmitted and has been found frequently in patients with chronic hepatitis C
      infection. To determine the impact of hepatitis G virus co-infection on morbidity
      and mortality following liver transplantation, we measured HGV RNA by polymerase
      chain reaction in pre and posttransplantation sera from a cohort of patients
      transplanted for chronic hepatitis C and a control group of patients transplanted
      for nonviral causes who were negative for hepatitis C virus (HCV) RNA in serum.
      The overall prevalence rate of HGV RNA in transplanted patients with chronic
      hepatitis C was 20.7%. HGV infection was present before transplantation in 13%
      while it appeared to have been acquired at the time of transplantation in 7.4%.
      Mean serum alanine aminotransferase activity, hepatic histological activity, and
      patient and graft survival were similar between HGV-positive and HGV-negative
      patients. The prevalence rate of HGV RNA in transplanted controls was 64% (P <
      .01) with a significantly higher rate of acquisition of HGV infection following
      transplantation (53%, P < .001) when compared with patients with chronic
      hepatitis C. Mean serum alanine aminotransferase activity was significantly lower
      in the control patients with HGV infection alone following transplantation than
      in patients co-infected with hepatitis C (37 +/- 9 vs. 70 +/- 33 U/L, P < .01).
      Thus, HGV is frequently found in transplantation patients co-infected with
      hepatitis C although it appears to have minimal clinical impact. In patients
      transplanted for nonviral causes of end-stage liver disease, a high rate of
      hepatitis G acquisition at the time of transplantation may occur but does not
      appear to predispose to chronic hepatitis.

PMID- 9141452
TI  - Ischemia-reperfusion: the liver under stress.

PMID- 9141453
TI  - Are stress proteins part of a cell's solution to toxicity or are they part of the
      problem?

PMID- 9141454
TI  - Hepatopulmonary syndrome versus portopulmonary hypertension: distinctions and
      dilemmas.

PMID- 9141455
TI  - GB virus C, hepatitis G virus, or human orphan flavivirus?

PMID- 9141456
TI  - The 18th United States-Japan Joint Hepatitis Panel Meeting.

PMID- 9141457
TI  - First pass metabolism of ethanol: gastric or hepatic, mountain or molehill?

PMID- 9141458
TI  - IL-6, a key cytokine in liver regeneration.

PMID- 9141459
TI  - Clinical hepatology: alcoholic liver disease, not viral hepatitis, predominates
      in South Wales.

PMID- 9141460
TI  - Towards a unified model of tumor suppression: lessons learned from the human
      patched gene.

PMID- 9141461
TI  - Cdc25 protein phosphatases in cell proliferation.

PMID- 9141462
TI  - Studies of neoplasia in the Min mouse.

PMID- 9141463
TI  - Everything you have ever wanted to know about Yin Yang 1......

PMID- 9141464
TI  - Whitehead Symposium on cancer.

PMID- 9141465
TI  - Gene therapy 1996.

PMID- 9141466
TI  - Cancer genetics and tumor suppressor genes. Sponsored by Cold Spring Harbor
      Laboratory--August 14-18, 1996.

PMID- 9141467
TI  - Maturation of cancer vaccines. A meeting report on 'Cancer Vaccines 1996,'
      sponsored by the Cancer Research Institute, held October 7-9, 1996.

PMID- 9141468
TI  - DNA replication under the Rigi Kulm. EMBO workshop on 'Molecular Biology of DNA
      replication', Weggis, Switzerland, 8-13 September 1996.

PMID- 9141469
TI  - Mechanism of p53 degradation.

PMID- 9141470
TI  - Autocatalytic processes in cooperative mechanisms of prion diseases.
AB  - According to the leading theory, the agent responsible for prion diseases would
      be the conformational isomer PrP(Sc) of a cellular protein PrP(C), the pathogenic
      form PrP(Sc) multiplying by converting the normal protein into a likeness of
      itself. The pathogenic isoform could catalyze the conformational transition so
      that the process, taken as a whole, is autocatalytic. However, in this simple but
      atypic model, unrealistic values of rate parameters are needed in order to
      account for the kinetics of the propagation of prion diseases. In this paper, I
      show that these limits can be overcome by assuming that catalysis proceeds
      through a multimeric assembly of the pathogenic isoform of the prion protein.
      Such a structure would indeed be able to provide cooperativity both at the
      assembly and conformational change levels, strongly reinforcing the autocatalytic
      character of the activated process. Moreover, such a property is a prerequisite
      to endow the metabolic system with dynamic bistability. Together with a good
      agreement regarding experimental data, this analysis is closely akin to
      Griffith's original idea concerning the thermodynamic conditions required for
      autocatalyzed modifications of any protein.

PMID- 9141471
TI  - Role of Rac GTPase in the nuclear signaling by EGF.
AB  - The role of Rac in epidermal growth factor (EGF)-induced c-fos serum response
      element (SRE) activation was examined in Rat-2 fibroblast cells. By reporter gene
      analysis following transient or stable transfections with pEXV-RacN17 encoding a
      dominant-negative mutant of Rac, EGF-induced activation of c-fos SRE-luciferase
      gene was shown to be selectively inhibited, suggesting that Rac activity is
      necessary for the full activation of SRE by EGF. Our further study to analyze the
      downstream mediator of Rac in EGF-signaling cascade demonstrated that there is a
      functional link between Rac and phospholipase A2 (PLA2) activation and further
      that PLA2 mediates, at least partly, the Rac signaling to SRE. Together, our
      results point to a critical role of Rac and Rac-activated PLA2 in the EGF
      signaling cascade to c-fos SRE. We propose that 'Rac-PLA2' cascade is one of the
      major signaling pathways by which EGF stimulates c-fos SRE.

PMID- 9141472
TI  - Evidence for the formation of an unusual ternary complex of rabbit liver EF
      1alpha with GDP and deacylated tRNA.
AB  - Eukaryotic translation elongation factor 1alpha is known to interact in GTP-bound
      form with aminoacyl-tRNA promoting its binding to the ribosome. In this paper
      another ternary complex [EF-1alpha*GDP*deacylated tRNA], never considered in
      widely accepted elongation schemes, is reported for the first time. The formation
      of this unusual complex, postulated earlier (FEBS Lett. (1996) 382, 18-20), has
      been detected by four independent methods. [EF-1alpha*GDP]-interacting sites are
      located in the acceptor stem, TpsiC stem and TpsiC loop of tRNA(Phe) and
      tRNA(Leu) molecules. Both tRNA and EF-1alpha are found to undergo certain
      conformational changes during their interaction. The ability of EF-1alpha to form
      a complex with deacylated tRNA indicates that the factor may perform an important
      role in tRNA and aminoacyl-tRNA channeling in higher eukaryotic cells.

PMID- 9141473
TI  - High affinity interaction of mouse DNA topoisomerase I with di- and
      trinucleotides corresponding to specific sequences of supercoiled DNA cleaved
      chain.
AB  - Recently mouse DNA topoisomerase I (topo) was shown to possess high affinity for
      a single-stranded AAGACTTAG nonanucleotide (K(i) = 2.0 microM) corresponding to
      the scissile strand of the minimal DNA duplex, which is necessary for cleavage of
      supercoiled DNA. In order to determine the most important part of the above
      sequence for the DNA recognition by topo, the interactions of the enzyme with a
      set of extremely short (2-5 nucleotides in length) oligonucleotides corresponding
      to different parts of the nonanucleotide have been investigated. The affinities
      of different oligonucleotides corresponding to the CTTAG part of the sequence
      (K(i) = 0.13-0.92 mM) were shown to be significantly lower than that for the AAGA
      tetranucleotide (K(i) = 9.0 microM). Topo effectively recognized even short
      oligonucleotides containing only two or three bases (AGA and pAG, K(i) = 20 and
      50 microM). We suppose that oligonucleotides having a high afffinity to the
      enzyme can offer a unique opportunity for the rational design of topoisomerase
      targeting drugs.

PMID- 9141474
TI  - Kinetics of calcium and calmodulin-dependent protein kinase III from embryonic
      chicken leg muscle cells.
AB  - Embryonic chicken muscle cells (CELM) contain the calmodulin-dependent protein
      kinase that specifically phosphorylates eukaryotic elongation factor 2. The
      kinase requires Ca2+ and maximum activity in CELM was observed at 10 microM Ca2+.
      The ATP concentration required for half the maximum activity of CaM PKIII in CELM
      was calculated to be 0.15 mM. In CELM, dephosphorylation of eEF-2 was catalyzed
      by phosphoprotein phosphatase PP2A alone. The activity of PP2A was relatively low
      and the half-life of added phosphorylated eEF-2 was more than 15 min. Due to the
      low phosphoprotein phosphatase activity, inhibition of the PP2A activity by
      addition of okadaic acid had little effect on the eEF-2 phosphorylation kinetics.

PMID- 9141475
TI  - Keratin expression and its significance in five cultured melanoma cell lines
      derived from primary, recurrent and metastasized melanomas.
AB  - With the exception of two cases, keratin is not expressed in cultured human
      melanoma cells. Using 2D-PAGE, immunological and electron microscopic analyses,
      we found keratin subunits in five established cultured cell lines derived from
      primary, recurrent and metastasized melanomas. The keratin subunits were composed
      of K1, K5, K10, K14, K15 and K18 in all cell lines examined, together with
      vimentin. In addition, K8, K16 and K18 expression were demonstrated in recurrent
      and metastasized cell lines. The results of the present and our previous study
      [Katagata Y, et al. J Dermatol Sci 1996;13:219-227] indicate that expression of
      keratin in melanoma cells may be a universal phenomenon. A specific increase in
      the proportion of K5 among the keratin subunits was suggestive of the nature of
      melanoma cells. Moreover, we detected two polypeptides that migrated on 2D-PAGE
      at positions which did not correspond to those of any keratin subunit. The amino
      acid sequences of these two polypeptides were determined; one was the human ATP
      synthase alpha-chain but the other did not match any known polypeptide in our
      homology search.

PMID- 9141476
TI  - Scavengase p20: a novel family of bacterial antioxidant enzymes.
AB  - A novel antioxidant enzyme designated scavengase p20 was identified in various
      pathogenic bacteria through database searching for sequences strikingly
      homologous to a recently discovered Escherichia coli thiol peroxidase p20. The
      direct biochemical evidence for the existence of scavengase p20 in Haemophilus
      influenzae, Streptococcus pneumoniae and Helicobacter pylori was provided by
      protein microsequencing and by in vitro assays for antioxidant activities.
      Overlapping genes encoding scavengase p20 and superoxide dismutase were
      recognized in H. pylori and their functional implications are discussed.

PMID- 9141477
TI  - A structural tree for proteins containing 3beta-corners.
AB  - A structural tree for beta-proteins with predominantly orthogonal beta-sheet
      packing has been constructed. The 3beta-corner, a structural motif that recurs in
      proteins of this class, is taken as a root structure of the tree. The 3beta
      corner can be represented as a triple-stranded beta-sheet folded on to itself so
      that its two beta-beta-hairpins are packed approximately orthogonally in
      different layers and the central strand bends by approximately 90 degrees in a
      right-handed direction when passing from one layer to the other. The larger
      protein structures are obtained by stepwise addition of beta-strands to the root
      3beta-corner taking into account a restricted set of rules inferred from known
      principles of protein structure. The protein structures that can be obtained in
      this way are grouped into one structural class and those found in branches of the
      structural tree into subclasses.

PMID- 9141478
TI  - Comparison of the amide proton exchange behavior of the rapidly formed folding
      intermediate and the native state of an antibody scFv fragment.
AB  - We have investigated the stability of backbone amide protons of the intermediate
      and the native state of the scFv fragment of an antibody. Stopped flow
      experiments analyzed by MS and NMR detected the formation of an exchange
      protected intermediate within the deadtime of the stopped flow apparatus (17 ms).
      H/D exchange rates of the native protein identified a number of very stable
      backbone amide protons in the V(L) and the V(H) domains. In the V(L) domain, this
      slowly exchanging core of the scFv fragment is similar to the folding core of the
      intermediate, while the V(H) domain possesses a great number of very stable amide
      protons which are not stabilized to a significant degree in the folding
      intermediate of the scFv fragment.

PMID- 9141479
TI  - The crystal structure of human cathepsin L complexed with E-64.
AB  - We have determined the three dimensional structure of the complex of human
      cathepsin L and E-64, an irreversible inhibitor of cysteine proteases, at 2.5 A
      resolution. The overall structure was similar to that of other known cysteine
      proteases and apparently identical to the mature region of procathepsin L. The
      electron density for E-64 is clearly visible except for the guanidinobutane
      moiety. From comparison of the active sites of cathepsin L and B, we found the
      following: (1) The S' subsites of cathepsin L and B are totally different because
      of the 'occluding loop' lying on the end of the S' subsites of cathepsin B. (2)
      The S2 pocket of cathepsin L is shallow and narrow compared to that of cathepsin
      B. (3) The S3 subsites of the two enzymes are more similar than the other
      subsites, but cathepsin L may accommodate a more bulky group at this site.
      Knowledge of the active site structure of cathepsin L should be helpful for the
      structure-based design of potent and specific inhibitors which are of therapeutic
      importance.

PMID- 9141480
TI  - Three different GB virus C/hepatitis G virus genotypes. Phylogenetic analysis and
      a genotyping assay based on restriction fragment length polymorphism.
AB  - The 5'-untranslated region (5'-UTR) sequences of 33 GB virus C/hepatitis G virus
      (GBV-C/HGV) obtained from different geographic areas were determined through
      reverse-transcription polymerase chain reaction and dideoxy chain termination
      sequencing, the alignment of sequences, the estimation of the number of
      nucleotide substitution per site, and construction of phylogenetic trees. The 5'
      UTR of GBV-HGV was found to be heterogeneous, with 70.9-99.5% homology. Three
      distinct phylogenetic branches were observed consistently in all phylogenetic
      trees. GBV-C is the prototype for one, HGV for another, and there is a new branch
      which consisted of GBV-C/HGV isolates from Asia. Genotype-specific restriction
      sites for the restriction enzymes, ScrFI and BsmFI, were identified, and a simple
      restriction fragment polymorphism analysis was developed for genotyping. These
      data provide evidence that GBV-C/HGV consists of three different genotypes. Our
      simple genotyping assay will also provide a tool for epidemiological studies of
      GBV-C/HGV infection.

PMID- 9141481
TI  - A novel putative G-protein-coupled receptor expressed in lung, heart and lymphoid
      tissue.
AB  - cDNA encoding a novel putative G-protein-coupled receptor, named LyGPR
      (lymphocyte derived G-protein-coupled receptor) was cloned using a reverse
      transcription-PCR approach. The LyGPR amino acid sequence is 375 residues long
      and shows similarity (about 30-35% identity) both to the angiotensin receptors
      and members of the chemokine receptor family. Northern blot analysis revealed a
      3.1-kb LyGPR transcript expressed predominantly in lung, heart and lymphoid
      tissues. LyGPR expression was also detected in the pre-B acute lymphoblastoid
      leukemia cell lines Reh and Nalm-6, in the Burkitt's lymphoma line Daudi, and in
      hematopoietic progenitor cells from bone marrow, as well as in B cells, T cells
      and monocytes from peripheral blood.

PMID- 9141482
TI  - Construction and expression in the yeast Pichia pastoris of functionally active
      soluble forms of the human costimulatory molecules B7-1 and B7-2 and the B7
      counter-receptor CTLA-4.
AB  - We have generated soluble recombinant forms of the costimulatory molecules B7-1
      and B7-2, and their counter-receptor CTLA-4 using a yeast Pichia pastoris
      expression system. Fragments comprising the extracellular domains of human B7-1,
      B7-2, and CTLA-4 molecules were expressed at high levels and could be purified
      from culture supernatants following a simple one-step purification protocol. The
      recombinant proteins retained their functionality and specific binding to their
      natural counterparts could be demonstrated by FACS analysis. In T cell
      proliferation assays costimulatory activity of immobilized B7-1 and B7-2 proteins
      in the presence of an anti-CD3 antibody was observed with the B7-1 protein being
      more potent than B7-2.

PMID- 9141483
TI  - Characterization of an intradiol dioxygenase involved in the biodegradation of
      the chlorophenoxy herbicides 2,4-D and 2,4,5-T.
AB  - Hydroxyquinol 1,2-dioxygenase, an intradiol dioxygenase, which catalyzes the
      cleaving of the aromatic ring of hydroxyquinol, a key intermediate of 2,4-D and
      2,4,5-T degradation, was purified from Nocardioides simplex 3E cells grown on 2,4
      D as the sole carbon source. This enzyme exhibits a highly restricted substrate
      specificity and is able to cleave hydroxyquinol (K(m) for hydroxyquinol as a
      substrate was 1.2 microM, V(max) 55 U/mg, K(cat) 57 s-1 and K(cat)/K(m) 47.5
      microM s-1), 6-chloro- and 5-chlorohydroxyquinol. Different substituted catechols
      and hydroquinones are not substrates for this enzyme. This enzyme appears to be a
      dimer with two identical 37-kDa subunits. Protein and iron analyses indicate an
      iron stoichiometry of 1 iron/65 kDa homodimer, alpha2 Fe. Both the electronic
      absorption spectrum which shows a broad absorption band with a maximum at 450 nm
      and the electron paramagnetic resonance spectra are consistent with a high-spin
      iron(III) ion in a rhombic environment typical of the active site of intradiol
      cleaving enzymes.

PMID- 9141484
TI  - The effect of neuropeptides kyotorphin and neokyotorphin on proliferation of
      cultured brown preadipocytes.
AB  - Stimulation of DNA and protein synthesis in brown preadipocytes by 1 microM
      neokyotorphin in serum-containing media was comparable with the effect of 1
      microM norepinephrine. In serum-free medium a decrease and a shift of the maximal
      effect to lower concentration of neokyotorphin were observed. Kyotorphin had no
      effect on cell proliferation in either medium; however, 0.01-1 microM kyotorphin
      inhibited the cell proliferation stimulated by 1 microM norepinephrine.
      Norepinephrine and both peptides stimulated comparable Ca2+ rise in freshly
      isolated brown preadipocytes. The effects of neokyotorphin and norepinephrine
      were additive, whereas 0.03-0.3 microM kyotorphin blocked the action of 3 microM
      norepinephrine. The peptides did not affect the cAMP level in non-stimulated or
      norepinephrine-stimulated cultured cells. The effects of the peptides on the
      brown fat cell cultures indicate that peripheral tissue cells contain receptors
      for these neuropeptides.

PMID- 9141485
TI  - The packaging capacity of adeno-associated virus (AAV) and the potential for wild
      type-plus AAV gene therapy vectors.
AB  - Because of its ability to integrate chromosomally and its non-pathogenic nature,
      adeno-associated virus (AAV) has significant potential as a human gene therapy
      vector. Here we investigate the maximum amount of DNA which can be inserted into
      the AAV genome and still allow efficient packaging into an infectious virus
      particle. Altered wild-type AAV genomes were constructed with inserts, which
      increased in size by 100 bp, ligated at map unit 96. These large wild-type-plus
      genomes were able to replicate and produce infectious virus, at levels slightly
      reduced but comparable to normal sized wild type, until the insert size reached 1
      kb. These data indicate that the maximum effective packaging capacity of AAV is
      approximately 900 bp larger than wild type, or 119%. Furthermore, it is
      demonstrated that these large AAV genomes are able to latently infect cells by
      chromosomal integration as does wild-type AAV. These data suggest that therapy
      vectors carrying a foreign gene of 900 bp or less can be generated from AAV, by
      ligation into non-essential locations, and result in a recombinant AAV virus with
      a fully wild-type phenotype. Such wild-type-plus AAV vectors will have both
      advantages and disadvantages over defective recombinant AAV virus - the most
      important advantages being the ease in which high titers of infectious virus can
      be generated and the ability to specifically integrate within chromosome 19. Once
      the concern subsides over the presence of wild-type AAV in clinical applications,
      wild-type AAV vectors may find specific application niches for use in human gene
      therapy.

PMID- 9141486
TI  - Identification of a vitamin K-dependent carboxylase in the venom duct of a Conus
      snail.
AB  - Peptides from the venom ducts of cone snails (genus Conus) contain gamma
      carboxyglutamate residues. The gamma-glutamyl carboxylase responsible for this
      post-translational modification is localized in the microsomal fraction, strictly
      dependent on vitamin K, activated by ammonium sulfate, and is associated with
      endogenous substrate. The K(m) of the enzyme for vitamin K is comparable to that
      for the bovine carboxylase. However, a propeptide containing substrate related to
      the blood coagulation protein factor IX, a highly efficient substrate for the
      bovine enzyme, was poorly carboxylated by the Conus enzyme, suggesting
      differences in gamma-carboxylase recognition signal sequences and/or structural
      requirements at the carboxylation site.

PMID- 9141487
TI  - Laccase is essential for lignin degradation by the white-rot fungus Pycnoporus
      cinnabarinus.
AB  - The white-rot fungus, Pycnoporus cinnabarinus, provides an excellent model
      organism to elucidate the controversial role of laccase in lignin degradation. P.
      cinnabarinus produces laccase in one isoform as the predominant phenoloxidase in
      ligninolytic cultures, and neither LiP nor MnP are secreted. Yet, P. cinnabarinus
      degrades lignin very efficiently. In the present work, we show that laccase-less
      mutants of P. cinnabarinus were greatly reduced in their ability to metabolize
      14C ring-labeled DHP. However, 14CO2 evolution in these mutant cultures could be
      restored to levels comparable to those of the wild-type cultures by addition of
      purified P. cinnabarinus laccase. This clearly indicates that laccase is
      absolutely essential for lignin degradation by P. cinnabarinus.

PMID- 9141488
TI  - Myosin as cofactor and substrate in fibrinolysis.
AB  - Myosin accelerates plasminogen activation by tissue-type plasminogen activator
      (tPA), and is degraded extensively by plasmin. Myosin binds both tPA and
      plasminogen, and enhances activation of des1-77-plasminogen by tPA but not by
      urokinase-type plasminogen activator (uPA). Myosin decreases K(M) and increases
      k(cat) for des1-77-plasminogen activation by tPA, to yield catalytic efficiencies
      in excess of 8000 M-1 s-1. The effect of myosin is attributed to its C-terminal
      portion, the myosin rod. With a K(M) of 3 microM, myosin is a high-affinity
      substrate for plasmin. The findings indicate that myosin is a cofactor for
      plasminogen activation and a substrate for plasmin.

PMID- 9141489
TI  - Sphingosine induces apoptosis in androgen-independent human prostatic carcinoma
      DU-145 cells by suppression of bcl-X(L) gene expression.
AB  - Our recent studies have suggested that sphingosine, an endogenous protein kinase
      C (PKC) inhibitor, may mediate apoptosis induced by a phorbol ester (PMA) in
      human promyelocytic leukemia HL-60 cells [Ohta et al. Cancer Res. 1995;55:691
      697], and that the apoptotic induction by both PMA and sphingosine is accompanied
      by down-regulation of bcl-2, a gene which acts to prevent apoptotic cell death
      [Sakakura et al. FEBS Lett. 1996;397:177-180]. In this study, we examined the
      sphingosine-induced apoptosis of the androgen-independent human prostatic
      carcinoma cell line DU-145, which expresses bcl-X(L) and Bax but not bcl-2, and
      found that treatment of DU-145 cells with sphingosine suppressed bcl-X(L) in both
      mRNA and protein levels but did not change bax expression at all. In contrast, in
      apoptotic cells treated with a PKC inhibitor, staurosporine, no effect on bcl
      X(L) or bax expression was observed. The initial metabolites of sphingosine in
      the cells, ceramide and sphingosine 1-phosphate, failed to induce apoptosis.
      These results indicate that, in DU-145 cells, sphingosine, but not its
      metabolites, induces apoptosis through down-regulation of bcl-X(L), independently
      of PKC inhibition. Our present results, together with previous observations,
      strongly suggest that apoptosis regulatory genes differ according to cell type
      and apoptosis induction through sphingosine is accompanied by inhibition of
      either bcl-2 or bcl-X(L) activity in these cells.

PMID- 9141490
TI  - The S.//.A.IG amino acid motif is present in a replication dependent late H3
      histone variant of P. lividus sea urchin.
AB  - A novel gene encoding a new H3 histone varian (H3L) has been identified in P.
      lividus sea urchin embryo. It encodes a H3 histone protein showing the S.//.A.IG
      amino acid motif typical of the replication independent H3.3 variants but in a
      mRNA showing the 3' terminal stem-loop nucleotide sequence that is typical of the
      replication dependent variants. The gene is intronless, the corresponding short
      transcript is non-polyadenyl ated and its expression is replication dependent
      with a timing of late variant. The new H3 variant is expressed as a minor
      component with respect to a major replication dependent late H3 histone here
      identified by partial cDNA sequence. These results show that classification of
      histones in replication dependent and independent variants only on the basis of
      their amino acid sequences should be reconsidered.

PMID- 9141491
TI  - Partial purification and characterization of a jasmonic acid conjugate cleaving
      amidohydrolase from the fungus Botryodiplodia theobromae.
AB  - A protein preparation from the mycelium of the tropical pathogenic fungus
      Botryodiplodia theobromae revealed a novel peptidase activity. This enzyme was
      capable of cleaving conjugates of jasmonic acid with alpha-amino acids. The
      protein was enriched 108-fold by gel filtration, ion exchange and hydrophobic
      interaction chromatography. The enzyme was found to be a glycoprotein with a
      molecular mass of about 107 kDa. The amidohydrolase seems to be very specific
      with regard to (-)-jasmonic acid and alpha-amino acids with (S)-configuration.

PMID- 9141492
TI  - Activation of the exchange factor Ras-GRF by calcium requires an intact Dbl
      homology domain.
AB  - Ras-GRF is a guanine nucleotide exchange factor that activates Ras proteins. Its
      activity on Ras in cells is enhanced upon calcium influx. Activation follows
      calcium-induced binding of calmodulin to an IQ motif near the N-terminus of Ras
      GRF. Ras-GRF also contains a Dbl homology (DH) domain C-terminal to the IQ motif.
      In many proteins, DH domains act as exchange factors for Rho-GTPase family
      members. However, we failed to detect exchange activity of this domain on well
      characterized Rho family members. Instead, we found that mutations analogous to
      those that block exchange activity of Dbl prevented Ras-GRF activation by
      calcium/ calmodulin in vivo. All DH domains are followed immediately by a
      pleckstrin homology (PH) domain. We found that a mutation at a conserved site
      within the PH domain following the DH domain also prevented Ras-GRF activation by
      calcium in vivo. These results suggest that in addition to playing a role as
      activators of Rho proteins, DH domains can also contribute to the coupling of
      cellular signals to Ras activation.

PMID- 9141493
TI  - Human recombinant tissue-factor pathway inhibitor prevents the proliferation of
      cultured human neonatal aortic smooth muscle cells.
AB  - Tissue-factor pathway inhibitor (TFPI) inhibits the procoagulant activity of the
      tissue-factor/factor VIIa complex. It was recently reported that TFPI prevented
      restenosis following tissue injury in a rabbit atherosclerotic model. In order to
      clarify the mechanism behind this successful prevention of restenosis, we
      investigated the direct effect of human recombinant TFPI (h-rTFPI) on the
      proliferation of cultured human neonatal aortic smooth muscle cells (hSMC). We
      found that h-rTFPI exhibits inhibitory activity toward hSMC proliferation, while
      h-rTFPI-C which lacks the carboxyl (C)-terminal region does not. Furthermore, we
      found that h-rTFPI binds to hSMCs with K(d) = 526 nM but that this binding is
      inhibited by the addition of the synthetic C-terminal peptide, Lys254-Met276, to
      h-rTFPI. Thus, the interaction of h-rTFPI with hSMCs mediated via the C-terminal
      region is responsible for the anti-proliferative action of h-rTFPI. On the basis
      of these results, we presume that the anti-proliferative effect of h-rTFPI in
      addition to its anticoagulant function plays a significant role in preventing
      restenosis following tissue injury.

PMID- 9141494
TI  - Identification of Mel1a melatonin receptors in the human embryonic kidney cell
      line HEK293: evidence of G protein-coupled melatonin receptors which do not
      mediate the inhibition of stimulated cyclic AMP levels.
AB  - Binding assays using 2-[125I]iodomelatonin revealed high-affinity, guanosine 5'-O
      (3-thiotriphosphate) sensitive, melatonin binding sites (B(max) 1.1 fmol/mg
      protein) in the human embryonic kidney cell line HEK293. Competition studies
      using the selective melatonin receptor antagonist luzindole and RT-PCR techniques
      identified these sites as human Mel1a melatonin receptors. Challenge of HEK293
      cells with 1 microM melatonin had no effect on forskolin stimulated cyclic AMP
      levels, whereas in HEK293 cells engineered to stably over-express the human Mel1a
      melatonin receptor (B(max) > 400 fmol/mg protein) melatonin dose-dependently
      inhibited stimulated cyclic AMP levels (IC50 7.7 pM). These data may indicate
      that certain tissues, expressing low levels of G protein-coupled melatonin
      receptors, do not display melatonin mediated inhibition of cAMP.

PMID- 9141495
TI  - Biomedical research: a Louisiana Purchase for the 21st Century.

PMID- 9141496
TI  - Hepatic canalicular membrane 4: expression of the multidrug resistance genes in
      the liver.
AB  - The liver is presented with a diverse set of nutrients, endogenous metabolites,
      and xenobiotics it must process for movement to their correct physiologic
      destinations. These compounds are transported by specific mechanisms that move
      their substrates, often against a concentration gradient. Several hepatic
      transporters have been identified such as the multispecific anion transporter,
      cMOAT, bile acid transporters, ion-motive ATPases, glutathione transporters,
      purine transporters, and the multidrug resistance-related protein, MRP. This
      review focuses on the hepatic regulation of the multidrug resistance genes that
      encode the P-glycoprotein transporters. P-glycoproteins are ATP-dependent
      integral membrane proteins that have diverse functions such as conferring
      resistance toward chemotherapeutic drugs and phospholipid movement. The
      expression of the multidrug resistance genes is regulated in a tissue-specific
      pattern and can be induced by exposure to chemotherapeutic drugs as well as
      cytotoxic xenobiotics. The specific molecular mechanisms that govern expression
      of these genes in normal and neoplastic cells are currently being unraveled.

PMID- 9141497
TI  - Sulfation and sulfotransferases 4: bioactivation of mutagens via sulfation.
AB  - Sulfation is a common final step in the biotransformation of xenobiotics and is
      traditionally associated with inactivation. However, the sulfate group is
      electron-withdrawing and may be cleaved off heterolytically in some molecules,
      leading to an electrophilic cation. The stable heterologous expression of
      sulfotransferases in indicator cells of standard mutagenicity tests has
      substantially improved the accessibility of this activation pathway.
      Sulfotransferase-mediated genotoxic effects have been demonstrated for numerous
      benzylic alcohols derived from polycyclic aromatic hydrocarbons and various
      aromatic hydroxylamines. Also, hycanthone (a benzylic alcohol), alpha
      hydroxytamoxifen (an allylic alcohol), 1'-hydroxysafrole (an allylic/benzylic
      alcohol), and 2-nitropropane are activated to genotoxicants by sulfotransferases.
      Various reactive sulfate conjugates show strong mutagenic effects only when they
      are generated directly within the indicator cell, due to their inefficient
      penetration of cell membranes. In other cases, secondary membrane-penetrating
      reactive species are formed from sulfuric acid esters by displacement reactions
      with medium components, such as chloride or amino acids. Reaction with water
      regenerates the alcohol, which becomes available for a new cycle of activation.
      Different sulfotransferases from the same species as well as related forms from
      rat and human differ in their substrate specificities and tissue distributions.
      These characteristics and reactivities of the sulfate conjugates formed may
      explain organotropic effects of the compounds activated via sulfotransferases.

PMID- 9141498
TI  - Aging processes, DNA damage, and repair.
AB  - The second triennial FASEB Summer Research Conference on "Clonal Senescence and
      Differentiation" (August 17-22, 1996) focused on the interrelationships between
      aging processes and DNA damage and repair. The attendees represented a cross
      section of senior and junior investigators working in fields ranging from classic
      cellular gerontology to yeast and nematode models of aging to basic mechanisms of
      DNA damage and repair. The meeting opened with a keynote address by Dr. Bruce
      Ames that emphasized the documented relationships between oxidative damage,
      cancer, and aging. This was followed by eight platform sessions, one poster
      discussion, one featured presentation, and an after-dinner address. The following
      sections highlight the key points discussed.

PMID- 9141499
TI  - Sequence motifs for calmodulin recognition.
AB  - Calmodulin (CaM) is recognized as a major calcium sensor and orchestrator of
      regulatory events through its interaction with a diverse group of cellular
      proteins. Many investigations have focused on defining the region of interaction
      between CaM and its cellular targets and the action of CaM on target protein
      function. Because CaM can bind with high affinity to a relatively small alpha
      helical region of many proteins, success in clearly defining the essential
      elements of CaM binding motifs seems feasible and should provide a means of
      identifying CaM binding proteins. Three recognition motifs for CaM interaction
      are discussed in the context of experimental investigations of a variety of CaM
      target proteins. A modified version of the IQ motif as a consensus for Ca2+
      independent binding and two related motifs for Ca2+-dependent binding, termed 18
      14 and 1-5-10 based on the position of conserved hydrophobic residues, are
      proposed. Although considerable sequence diversity is observed among the
      different binding regions, these three classes of recognition motifs exist for
      many of the known CaM binding proteins.

PMID- 9141500
TI  - Connectin/titin, giant elastic protein of muscle.
AB  - The structure and function of the giant elastic protein connectin/titin are
      described on the basis of recent investigations. The 3000 kDa protein links the Z
      line to the myosin filament in striated muscle sarcomeres. The NH2-terminal
      region of connectin filament is involved in the Z line binding, and the COOH
      terminal region is bound onto the myosin filament with an overlap between the
      counter-connectin filaments at the M line. The PEVK region in the I band is shown
      to be mainly responsible for passive tension generation. The longitudinal
      continuity of myosin-, actin-free sarcomeres is explained by the linkage of freed
      connectin filaments extending from both sides of the Z lines in a sarcomere. The
      role of connectin in myofibrillar differentiation and the biodiversity of
      connectin-related proteins in the animal kingdom are briefly reviewed.

PMID- 9141501
TI  - G-protein-coupled receptors: molecular mechanisms involved in receptor activation
      and selectivity of G-protein recognition.
AB  - G-protein-coupled receptors (GPCRs) play fundamental roles in regulating the
      activity of virtually every body cell. Upon binding of extracellular ligands,
      GPCRs interact with a specific subset of heterotrimeric G-proteins that can then,
      in their activated forms, inhibit or activate various effector enzymes and/or ion
      channels. Molecular cloning studies have shown that GPCRs form one of the largest
      protein families found in nature, and it is estimated that approximately 1000
      different such receptors exist in mammals. The molecular mechanisms involved in
      GPCR function, particularly the molecular modes of receptor activation and G
      protein recognition and activation, have therefore become the research focus of
      an ever increasing number of laboratories. This review will summarize and attempt
      to integrate recent data derived from structural, molecular genetic, biochemical,
      and biophysical studies that have shed new light on these processes.

PMID- 9141502
TI  - Mammalian membrane metallopeptidases: NEP, ECE, KELL, and PEX.
AB  - Mammalian cell-surface peptidases participate in the postsecretory processing and
      metabolism of neuropeptides and peptide hormones. Neutral endopeptidase-24.11
      (NEP) is the prototype of a family of zinc metallopeptidases that also includes
      the endothelin-converting enzymes (ECE) and which are structurally related to the
      bacterial enzymes thermolysin and lactococcal endopeptidase. Two other mammalian
      gene products exhibit strong homology with NEP: the erythrocyte cell-surface
      antigen, KELL; and the putative product of the PEX gene, which has been
      associated with X-linked hypophosphatemic rickets. No enzymic activity has yet
      been attributed to KELL and PEX proteins, and they remain peptidases in search of
      a substrate. A wide range of biologically active peptide substrates has been
      described for NEP, of which the enkephalins and the atrial natriuretic peptide
      family have assumed greatest significance. Endothelin-converting enzyme catalyses
      the final step in the biosynthesis of the vasoconstrictor peptide, endothelin
      (ET). Like NEP, it is a type II integral membrane protein, but is expressed
      predominantly in endothelial cells. Isoforms of ECE (ECE-1alpha, ECE-1beta, and
      ECE-2) exist that differ in a number of characteristics. In particular, ECE-1,
      through the paracrine effects of ET-1, may contribute to the proliferation of
      smooth muscle after angioplasty and to the development of human atherosclerosis.
      Inhibitors of ECE and NEP may have important therapeutic applications in
      cardiovascular and renal medicine.

PMID- 9141503
TI  - Vascular development: cellular and molecular regulation.
AB  - The vascular system forms through a combination of vasculogenesis and
      angiogenesis. In vasculogenesis, vessels form de novo via the assembly of
      endothelial precursors called angioblasts, whereas in angiogenesis new vessels
      arise by migration and proliferation of endothelial cells from preexisting
      vessels. Although the two processes are distinct in some respects, recent
      evidence suggests that they share a number of regulatory mechanisms. The
      identification of a number of defined growth factors, observations of genetically
      manipulated mice, and the recognition of the importance of cell-cell interactions
      have greatly expanded our understanding of the regulation of vascularization. The
      paracrine actions of a variety of polypeptide growth factors, including platelet
      derived growth factor, vascular endothelial growth factor, transforming growth
      factor-beta, and the angiopoietins, appear to be orchestrated in a complex
      sequence of steps that lead to the development of the adult vascular system.
      Thus, communication between the forming vasculature and the tissue parenchyma, as
      well as interactions among cells of the vascular wall, all appear to influence
      vascular development and growth.

PMID- 9141504
TI  - On the virtual existence of superoxide anions in mitochondria: thoughts regarding
      its role in pathophysiology.

PMID- 9141505
TI  - CD10 plays a specific role in early thymic development.
AB  - Development of T lymphocyte is a complex process that depends on both
      thymocytestromal cell interactions and the production of soluble factors such as
      cytokines, peptides, and hormones. In many tissues, the concentration of active
      biological peptides is regulated locally by a specialized family of enzymes: the
      ectopeptidases. We show here that treatment of fetal thymic organ cultures (FTOC)
      with the specific CD10 (endopeptidase 24.11) inhibitors SCH 32615: (N-[L-(1
      carboxy-2-phenyl)ethyl]-L-phenylalanyl-beta-alanine), RB25: (N-(3
      [(hydroaxyamino)carbonyl]-2-benzylidene-1-oxopropyl]-N-glyci ne), and thymopentin
      (TP5) results in the inhibition of thymocyte differentiation. Each agent induces
      a significant decrease in the number of double positive (CD4+CD8+) cells in favor
      of the TN (TcR alpha beta-CD4-CD8-) population. RB25 also blocks T lymphocyte
      differentiation in FTOC when preinjected into pregnant mice. Finally, RB25 and
      TP5 were also shown to reduce the number of CD44+CD25- and CD44-CD25- thymocytes
      both in vitro and after preinjection in vivo in day 2 FTOC. Thus, agents that
      affect endopeptidase 24.11 activity impair T cell development both in vitro and
      in vivo. Our results show that the CD10 molecule plays a specific role in
      promoting early T cell development.

PMID- 9141506
TI  - Leptin gene is expressed in rat brown adipose tissue at birth.
AB  - The ob gene product leptin is secreted from adipose tissue. Leptin has dramatic
      effects on food intake and energy expenditure in rodents. Brown adipose tissue is
      the first form of adipose tissue to appear during development, and is present at
      birth in most species. The development of a leptin feedback system in early life
      and the relative role of the brown and white adipose tissues have not yet been
      revealed. We have investigated the expression of ob/leptin mRNA in brown adipose
      tissue around birth and with respect to feeding. Northern blotting analysis and
      in situ hybridization experiments demonstrated the presence of leptin mRNA in
      brown adipose tissue at 0, 18, and 24 h after birth. The leptin mRNA level was
      decreased at 8 h postpartum in fed animals and at 18 or 24 h in the absence of
      feeding. In addition, circulating leptin was detected in the plasma of newborn
      rats at 0, 10, or 24 h after birth, whereas it was not detectable in 10 h-old
      animals that did not suckle at their mother. The presence at birth of ob mRNA and
      circulating leptin, as well as the early effect of suckling on ob mRNA levels,
      suggests the precocious involvement of leptin in the control of food intake.

PMID- 9141507
TI  - Aerobic glycolysis by proliferating cells: a protective strategy against reactive
      oxygen species.
AB  - Our laboratory has reported that glucose is essential for glycolytic enzyme
      induction and proliferation of mitogen-activated rat thymocytes (41). Here we
      show that: 1) Resting thymocytes meet their ATP demand mainly by oxidative
      glucose breakdown (88%), whereas proliferating thymocytes produce 86% by
      glycolytic degradation of glucose to lactate and only 14% by oxidation to CO2 and
      water. 2) In contrast to nonstimulated resting thymocytes, production of PMA
      primed reactive oxygen species (ROS) in the proliferating cells is nearly
      abolished. 3) Consistent with this finding, no ROS formation is observed in
      proliferating human promyelocytic HL-60 cells, whereas differentiated,
      nonproliferating HL-60 cells exert a marked response upon priming with PMA. 4)
      The observed reduction of ROS formation by resting thymocytes incubated with
      pyruvate suggests a function of pyruvate as an H(2)O(2) scavenger. 5) The
      respiratory chain is a potential origin for ROS because inhibitors of the
      mitochondrial electron transport strongly reduce H(2)O(2) production by resting
      thymocytes. The results are discussed in the context of aerobic glycolysis by
      proliferating cells being a means to minimize oxidative stress during the phases
      of the cell cycle where maximally enhanced biosynthesis and cell division do
      occur.

PMID- 9141508
TI  - To sleep, perchance to eat.

PMID- 9141510
TI  - Extensive personal experience: adrenocortical tumors.

PMID- 9141509
TI  - Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role
      of sleep disturbance and obesity.
AB  - Excessive daytime sleepiness (EDS) and fatigue are frequent symptoms in the
      general population and the chief complaint of the majority of patients at Sleep
      Disorders Centers. There is evidence that the inflammatory cytokines tumor
      necrosis factor-alpha (TNF alpha), interleukin-1beta (IL-1beta), and IL-6 are
      involved in physiological sleep regulation and that their administration to
      humans is associated with sleepiness and fatigue. To explore whether plasma
      levels of TNF alpha, IL-1beta, and IL-6 are elevated in patients with EDS, we
      measured morning plasma levels of TNF alpha, IL-1beta, and IL-6 in 12 sleep
      apneics, 11 narcoleptics, 8 idiopathic hypersomniacs, and 10 normal controls. TNF
      alpha was significantly elevated in sleep apneics and narcoleptics compared to
      that in normal controls (P < 0.001 and P = 0.001, respectively). Plasma IL-1beta
      concentrations were not different between sleep disorder patients and controls,
      whereas IL-6 was markedly and significantly elevated in sleep apneics compared to
      that in normal controls (P = 0.028). The primary factor influencing TNF alpha
      values was the degree of nocturnal sleep disturbance, whereas the primary
      determinant for IL-6 levels was the body mass index. Our findings suggest that
      TNF alpha and IL-6 might play a significant role in mediating sleepiness and
      fatigue in disorders of EDS in humans.

PMID- 9141511
TI  - Low levels of follicle-stimulating hormone receptor-activation inhibitors in
      serum and follicular fluid from normal controls and anovulatory patients with or
      without polycystic ovary syndrome.
AB  - In patients with normogonadotropic anovulation, either with or without polycystic
      ovary syndrome (PCOS), factors interfering with FSH action may be involved in
      arrested follicle development. The aim of this study is to assess whether factors
      inhibiting FSH receptor activation are elevated in serum or follicular fluid from
      anovulatory patients, as compared with regularly cycling women. For this purpose,
      a Chinese hamster ovary cell line, stably transfected with the human FSH
      receptor, has been applied. FSH-stimulated cAMP secretion in culture medium was
      measured in the presence of serum or follicular fluid. Chinese hamster ovary
      cells were stimulated with a fixed concentration of FSH (3 or 6 mIU/mL) to mimic
      FSH levels in serum or follicular fluid. Samples were added in concentrations
      ranging from 3-90% vol/vol to approach protein concentrations occurring in serum
      or follicular fluid. In the presence of 10% vol/vol serum from regularly cycling
      women (n = 8), FSH-stimulated cAMP production was inhibited to 42 +/- 2% (mean +/
      SEM of 2 experiments, each performed in duplicate) of cAMP production in the
      absence of serum, whereas a similar cAMP level (up to 38 +/- 4% of the serum-free
      level) was observed at higher concentrations of serum (30-90% vol/vol). The
      inhibition of FSH-stimulated cAMP production in the presence of serum samples
      from normogonadotropic anovulatory patients, without (n = 13) or with (n = 16)
      PCOS, was similar to controls. Follicular fluid samples (n = 57) obtained during
      the follicular phase in 25 regularly cycling women and follicular fluid samples
      (n = 25) from 5 PCOS patients were tested in a slightly modified assay system. In
      the presence of 10 or 30% (vol/vol) follicular fluid, FSH-stimulated cAMP levels
      were decreased to 68 +/- 2% and 55 +/- 2% (mean +/- SEM of a single experiment in
      triplicate) of the cAMP levels in the absence of follicular fluid, respectively.
      There was no correlation between the degree of cAMP inhibition and follicle size,
      steroid content (androstenedione or estradiol concentrations), or menstrual cycle
      phase. Furthermore, no differences in inhibition were found, comparing PCOS
      follicles with size- and steroid content-matched follicles obtained during the
      normal follicular phase. It is concluded that inhibition of FSH receptor
      activation by proteins present in serum or follicular fluid is constant (60 and
      40%, respectively) and independent from the developmental stage of the follicle,
      either during the normal follicular phase or in patients with normogonadotropic
      anovulation. Inhibition of FSH receptor activation may be of limited significance
      for normal and arrested follicle development.

PMID- 9141512
TI  - Body composition and endocrine function in women with acquired immunodeficiency
      syndrome wasting.
AB  - The acquired immunodeficiency syndrome (AIDS) wasting syndrome is a devastating
      complication of human immunodeficiency virus (HIV) infection characterized by
      progressive weight loss and severe inanition. In men, the wasting syndrome is
      characterized by a disproportionate decrease in lean body mass and relative fat
      sparing. In contrast, relatively little is known about the gender-specific
      changes in body composition that characterize AIDS wasting in women. Three groups
      of women were studied to determine body composition and hormonal changes with
      respect to stage of wasting [nonwasting (NW; weight >90% ideal body weight;
      weight loss <10% of preillness maximum; n = 12), early wasting (EW; weight >90%
      ideal body weight; weight loss >10% of preillness maximum; n = 10), and late
      wasting (LW; weight <90%; n = 9)] and compared with a control group of 12,
      healthy, age-matched women. Weight loss averaged 6 +/- 6% (NW), 15 +/- 6% (EW),
      and 20 +/- 8% (LW) in the three groups. Lean, fat, and muscle masses were
      determined by dual energy x-ray absorptiometry and urinary creatinine excretion.
      Subjects were 36 +/- 5 yr of age (mean +/- SD) with a CD4 cell count of 379 +/-
      239 cells/mm3. The body mass index was 24.4 +/- 2.6 kg/m2 (NW), 22.2 +/- 1.2
      kg/m2 (EW), 18.2 +/- 2.0 kg/m2 (LW), and 24.3 +/- 2.6 kg/m2 (controls; P < 0.01,
      NW vs. EW; P < 0.0001, NW vs. LW). Lean body mass indexed for height was 15.7 +/-
      2.4 kg/m2 (NW), 14.8 +/- 2.0 kg/m2 (EW), and 13.7 +/- 1.2 kg/m2 (LW) and was
      decreased significantly only in the LW group (P < 0.05 vs. NW). Muscle mass was
      96% (NW), 94% (EW), and 78% (LW) of that predicted for height (P < 0.05, NW vs.
      LW). In contrast, fat mass indexed for height was decreased significantly among
      patients in both the EW and LW groups [8.7 +/- 1.9 kg/m2 (NW), 6.5 +/- 1.9 kg/m2
      (EW), and 3.7 +/- 1.4 kg/m2 (LW); P < 0.05, NW vs. EW; P < 0.001, NW vs. LW).
      Expressed as a percentage of the value in nonwasting HIV-positive controls (NW),
      the relative loss of fat was greater than the loss of lean mass with progressive
      degrees of wasting [EW, 25% vs. 6% (fat vs. lean); LW, 58% vs. 13%]. The
      prevalence of amenorrhea was 20% among study subjects [17% (NW), 10% (EW), and
      38% (LW)]. The percent predicted muscle mass was significantly lower in subjects
      with amenorrhea (74 +/- 8%) compared to that in eumenorrheic HIV-positive
      subjects (94 +/- 4%; P < 0.05). Estradiol levels were lower among subjects with
      amenorrhea (17.6 +/- 21.8 pg/mL) compared to eumenorrheic HIV-positive (48.9 +/-
      33.6 pg/mL) and control (68.3 +/- 47.6 pg/mL) subjects and did not correlate with
      body composition. Mean free testosterone, but not total testosterone, levels were
      decreased in subjects with EW and LW compared to those in age-matched healthy
      controls, but not compared with those in NW [0.9 +/- 0.6 ng/dL (NW), 0.7 +/- 0.4
      ng/dL (EW), 0.6 +/- 0.3 ng/dL (LW), and 2.0 +/- 2.4 ng/dL (controls); P < 0.05,
      EW vs. controls and LW vs. controls] and correlated with muscle mass (r = 0.37; P
      < 0.05). The percentages of women with free testosterone levels below the age
      adjusted normal range were 33% (NW), 50% (EW), and 66% (LW).
      Dehydroepiandrosterone sulfate levels were also low in the subjects with LW
      compared to those in the control group [98 +/- 85 microg/dL (NW), 102 +/- 53
      microg/dL (EW), 55 +/- 46 microg/dL (LW), and 132 +/- 68 microg/dL (controls); P
      < 0.05 LW vs. controls] and were correlated highly with free testosterone levels
      (r = 0.73; P < 0.00001) and also with muscle mass (r = 0.48; P < 0.01). These
      data demonstrate that women lose significant lean body and muscle mass in the
      late stages of wasting. However, in contrast to men, women exhibit a progressive
      and disproportionate decrease in body fat relative to lean body mass at all
      stages of wasting, consistent with gender-specific effects in body composition in
      AIDS wasting. (ABSTRACT TRUNCATED)

PMID- 9141513
TI  - Human saturated steroid 6alpha-hydroxylase.
AB  - This study was conducted to evaluate further the reaction catalyzed by the
      saturated steroid 6alpha-hydroxylase of extrahepatic human tissues. Progesterone
      and 5alpha-dihydroprogesterone (5alpha-DHP) are plasma-borne precursors of 5alpha
      pregnan-3alpha-ol-20-one, an anxiolytic/anesthetic steroid, and 5alpha-pregnan
      3beta-ol-20-one in extrahepatic human tissues. These two steroids are metabolized
      further by a saturated steroid 6alpha-hydroxylase enzyme(s) that is distinct from
      the cytochrome P450 6alpha-hydroxylase that catalyzes the 6alpha-hydroxylation of
      delta4-3-ketosteroids such as progesterone, cortisol, and testosterone. Products
      of this saturated steroid 6alpha-hydroxylase, viz. 3beta/alpha,6alpha-dihydroxy
      5alpha-pregnan-20-ones, are major radiolabeled urinary metabolites (excreted as
      glucuronosides) of i.v. administered tritium-labeled 5alpha-DHP in women and men.
      T47-D human breast cancer cells, which are rich in saturated steroid 6alpha
      hydroxylase activity, were used as the enzyme source in this study. The greatest
      total and the highest specific activity of saturated steroid 6alpha-hydroxylase
      were localized in microsome-enriched preparations; enzyme activity was linear
      with incubation time up to 30 min and with microsome-enriched tissue protein
      concentrations between 0.05-0.5 mg/mL incubation mixture. The velocity of the
      reaction was similar in incubations in which the pH was varied from 6.0-8.0, and
      NADH and NADPH were equally effective in supporting the 6alpha-hydroxylation of
      5alpha-pregnan-3beta-ol-20-one and 5alpha-pregnan-3alpha-ol-20-one. The more
      efficient substrates for this enzyme were 5alpha-pregnan-3beta-ol-20-one and
      5alpha-pregnan-3alpha-ol-20-one, and the apparent Km (approximately 3.5
      micromol/L) and maximum velocity (approximately 150 pmol/min x mg microsome
      enriched protein) for these two substrates were indistinguishable. 5alpha
      Androstane-3beta,17beta-diol was less efficiently 6alpha-hydroxylated, and 5alpha
      androstane-3alpha,17beta-diol was an inefficient substrate. The addition of a
      variety of inhibitors of cytochrome P450 monooxygenases to the incubation
      mixtures did not diminish significantly the 6alpha-hydroxylation of 5alpha
      pregnan-3beta-ol-20-one, findings consistent with those of other investigators
      who suggested that human saturated steroid 6alpha-hydroxylase (of human prostate)
      is not a cytochrome P450.

PMID- 9141514
TI  - Tissue-specific expression of alpha and beta messenger ribonucleic acid isoforms
      of the human mineralocorticoid receptor in normal and pathological states.
AB  - Expression of the mineralocorticoid receptor (MR) is restricted to some sodium
      transporting epithelia and a few nonepithelial target tissues. Determination of
      the genomic structure of the human MR (hMR) revealed two different untranslated
      exons (1alpha and 1beta), which splice alternatively into the common exon 2,
      giving rise to two hMR mRNA isoforms (hMR alpha and hMR beta). We have
      investigated expression of hMR transcripts in renal, cardiac, skin, and colonic
      tissue samples by in situ hybridization with exon 1alpha and 1beta specific
      riboprobes, using an exon 2 probe as internal control. Specific signals for
      either exon 1alpha- and 1beta-containing mRNAs were detected in typically hMR
      expressing cells in all tissues analyzed. hMR alpha and hMR beta were present in
      distal tubules of the kidney, in cardiomyocytes, in enterocytes of the colonic
      mucosa, and in keratinocytes and sweat glands. Interestingly, although both
      isoforms appear to be expressed at approximately the same level, the relative
      abundance of each message compared with that of exon 2-containing mRNA strikingly
      differs among aldosterone target tissues, suggesting the possibility of other
      tissue-specific transcripts originating from alternative splicing. Finally,
      functional hypermineralocorticism was associated with reduced expression of hMR
      beta in sweat glands of two patients affected by Conn's and Liddle's syndrome,
      whereas normal levels of hMR isoforms were found in one case of
      pseudohypoaldosteronism. Altogether, our results indicate a differential, tissue
      specific expression of hMR mRNA isoforms, hMR beta being down-regulated in
      situations of positive sodium balance, independently of aldosterone levels.

PMID- 9141515
TI  - Cytochrome P450 1A2 is a hepatic autoantigen in autoimmune polyglandular syndrome
      type 1.
AB  - Autoantibodies directed against proteins of the adrenal cortex and the liver were
      studied in 88 subjects of Sardinian descent, namely six patients with autoimmune
      polyendocrine syndrome type 1 (APS1), 22 relatives of APS1 patients, 40 controls
      with other autoimmune diseases, and 20 healthy controls. Indirect
      immunofluorescence, using tissue sections of the adrenal cortex, revealed a
      cytoplasmatic staining pattern in 4 of 6 patients with APS1. Western blotting
      with adrenal mitochondria identified autoantigens of 54 kDa and 57 kDa, Western
      blotting with placental mitochondria revealed a 54-kDa autoantigen. The 54-kDa
      protein was recognized by 4 of 6 patients with APS1 both in placental and adrenal
      tissue, whereas the 57-kDa protein was detected only by one serum. Using
      recombinant preparations of cytochrome P450 proteins, the autoantigens were
      identified as P450 scc and P450 c17. One of six APS1 patients suffered from
      chronic hepatitis. In this patient, immunofluorescence revealed a centrolobular
      liver and a proximal renal tubule staining pattern. Western blots using
      microsomal preparations of human liver revealed a protein band of 52 kDa. The
      autoantigen was identified as cytochrome P450 1A2 by use of recombinant protein
      preparations. P450 1A2 represents the first hepatic autoantigen reported in APS1.
      P450 1A2 usually is not detected by sera of patients with isolated autoimmune
      liver disease and might be a hepatic marker autoantigen for patients with APS1.

PMID- 9141516
TI  - Idiopathic hypothalamic diabetes insipidus, pituitary stalk thickening, and the
      occult intracranial germinoma in children and adolescents.
AB  - We report nine consecutive children and adolescents [five females and four males;
      aged 2 yr 8 months (m) to 18 yr 1 m] studied over the last 5 yr with idiopathic
      central diabetes insipidus. In addition to vasopressin deficiency, anterior
      pituitary hormone deficiencies were detected, either on evaluation at
      presentation or during follow-up studies over the following 3 yr. Four patients
      had an increased concentration of plasma PRL. One patient had multiple pituitary
      hormone deficiencies at diagnosis, and two others developed the same by 21 m of
      follow-up. Brain magnestic resonance imaging scans, performed at presentation,
      were originally interpreted as normal in four of nine patients, except for
      absence of the bright posterior pituitary signal; after retrospective review, two
      of nine were considered normal. All of the brain magnetic resonance imaging (MRI)
      scans showed positive findings by 14 m of follow-up. The first abnormal finding
      in all patients was isolated pituitary stalk thickening. Evaluation of
      cerebrospinal fluid (CSF) for hCG was positive in three of eight evaluated
      patients; the three positive CSF values were found at presentation and 3 and 9 m
      after presentation. All eight patients assessed were negative for CSF alpha
      fetoprotein and cytology, and no patient had serum tumor markers. Transsphenoidal
      biopsy of the lesion in seven of nine patients showed a germinoma in six patients
      and inflammatory cells in one. The six patients with documented germinoma
      comprise 31% of the intracranial germinomas diagnosed in this age group at the
      University of California-San Francisco during the last 5 yr. The patient with
      mononuclear inflammatory cells on biopsy along with one other patient have had
      spontaneous resolution of their stalk thickening. So-called "idiopathic" central
      diabetes insipidus warrants close follow-up to determine the etiology, especially
      if anterior pituitary hormone deficiencies are detected. Normal brain MRI scans
      or scans that show isolated pituitary stalk thickening merit follow-up with
      serial contrast enhanced brain MRI for the early detection of an evolving occult
      hypothalamic-stalk lesion. CSF evaluation is recommended at presentation because
      elevated CSF hCG may precede MRI abnormalities.

PMID- 9141517
TI  - Gain in body fat is inversely related to the nocturnal rise in serum leptin level
      in young females.
AB  - Both genetic and environmental factors contribute to adolescent obesity. Evidence
      of a genetic basis for obesity development is substantial, although the exact
      mechanism of action has yet to be identified. The purpose of this study was to
      document the circadian rhythmicity of the serum leptin level in young females and
      to assess the impact of the change in body fat stores during growth on the
      nocturnal rise in the serum leptin level with implications for obesity traits.
      There was a significant rise in serum leptin at midnight and 0400 h, suggesting a
      diurnal variation in serum leptin concentrations (ANOVA F ratio = 6.2; P <
      0.0001). There was also a strong association between relative total body fat and
      the average daytime serum leptin level (r = 0.78; P < 0.0001). The percent
      increase in the nocturnal leptin concentration was inversely related to the
      percent gain in total body fat (r = 0.45; P < 0.024). Forward stepwise regression
      analysis selected the change in total body fat over a 6-month interval as the
      most powerful determinant of the percent increase in the nocturnal leptin
      concentration (partial R2 = 0.203; beta = -0.450; SE of beta = 0.186; t = -2.418;
      P < 0.024). If the lack of a nocturnal rise in serum leptin persists over a
      longer period of time, it may have implications for the development of obesity,
      presumably by inadequate suppression of nighttime appetite.

PMID- 9141518
TI  - MK-386, an inhibitor of 5alpha-reductase type 1, reduces dihydrotestosterone
      concentrations in serum and sebum without affecting dihydrotestosterone
      concentrations in semen.
AB  - Two isozymes (types 1 and 2) of 5alpha-reductase (5alphaR; EC 1.3.99.5), with
      differential tissue distribution, catalyze the reduction of testosterone (T) to
      dihydrotestosterone (DHT) in humans. This study examined sequentially increasing
      oral doses of MK-386 (4,7beta-dimethyl-4-aza-5alpha-cholestan-3-one), an
      azasteroid that specifically inhibits the human 5alphaR1 isozyme in vitro.
      Finasteride, a selective inhibitor of 5alphaR2, was included for comparison. One
      hundred men were evaluated in a double blind, randomized, placebo-controlled,
      sequential, increasing dose, parallel group trial. Ten to 20 subjects received MK
      386, and 2 to 5 received placebo in each of 6 panels. In 1 panel, 10 subjects
      received finasteride (5 mg), and 5 received placebo. Treatments were given once
      daily for 14 days, except in 1 panel in which MK-386 was administered 10 mg twice
      daily for comparison to 20 mg daily. Serum, sebum, and semen DHT concentrations
      and serum and sebum T concentrations were measured before and after treatment.
      The mean changes from baseline on day 14 for serum DHT after placebo and 0.1,
      0.5, 5, 20, and 50 mg MK-386 were 6.9%, 4.6%, -2.7%, -1.2%, -14.1% (P < 0.05 vs.
      placebo), and -22.2% (P < 0.05 vs. placebo), respectively. No significant
      alterations in serum T were observed after any dose of MK-386. Serum DHT fell
      65.8% from the baseline 14 days after finasteride treatment (P < 0.05 vs.
      placebo). The mean changes from baseline on day 14 in sebum DHT were 5.0%, 3.0%, 
      25.4% (P < 0.05 vs. placebo), -30.1% (P < 0.05 vs. placebo), and -49.1% (P < 0.05
      vs. placebo) for the placebo and 0.5, 5, 20, and 50 mg MK-386 groups,
      respectively. Finasteride also reduced sebum DHT, but to a lesser extent (-
      14.9%; P < 0.05 vs. placebo). Reciprocal increases in sebum T concentration were
      noted at doses of 5 mg or more of MK-386, but not with finasteride. The mean
      reduction in semen DHT with 5 mg finasteride was approximately 88% (P < 0.01 vs.
      placebo); no significant change in semen DHT was noted with 20 or 50 mg MK-386.
      Serum 3alpha-androstanediol glucuronide values were also reduced after the 20-
      and 50-mg MK-386 treatments in parallel with the changes in serum DHT. No
      meaningful changes were observed in serum LH after MK-386 treatment. MK-386 was
      generally well tolerated by all subjects; reversible aspartate
      aminotransferase/alanine aminotransferase elevations were observed in two
      subjects at the 50-mg dose. The differential responses in serum, sebum, and semen
      DHT concentrations associated with MK-386 and finasteride treatments are
      consistent with those changes anticipated for selective inhibitors of the human
      5alphaR isozymes. Dose-dependent suppression of sebum DHT by a 5alphaR1 inhibitor
      suggests the potential utility of such compounds in the treatment of acne.

PMID- 9141519
TI  - Increased arterial intima-media thickness in childhood-onset growth hormone
      deficiency.
AB  - Very little is known about the atherosclerotic risk in patients with childhood
      onset growth hormone deficiency (GHD). Such data may be relevant to
      reconstructing the natural course of the cardiovascular abnormalities associated
      with GHD. To this end, the intima-media thickness (IMT) of the carotid arteries
      and the vascular risk factors were evaluated in 14 childhood-onset GHD patients
      (age 25 +/- 1 yr, BMI 22 +/- 0.6 Kg/m2) and in 14 age-, sex-, and BMI-matched
      control subjects. IMT was greater in GHD patients (0.83 +/- 0.06 and 0.81 +/-
      0.06 mmol/L for the right and left carotid artery) than in controls (0.64 +/-
      0.03 and 0.64 +/- 0.04 mmol/L, P < 0.01 and P < 0.02, respectively). Serum total
      and lipoprotein cholesterol, and serum total triglycerides did not differ between
      the two groups. However, a significant increase in low density lipid
      triglycerides was present in GHD patients (0.27 +/- 0.02 mmol/L) compared with
      controls (0.19 +/- 0.01; P = 0.007). No difference was found in plasma fibrinogen
      and serum Lp(a) levels. Plasma glucose and insulin concentrations were similar in
      GHD and control subjects both in the fasted state and after an oral glucose load.
      In conclusion, young patients with childhood-onset GHD show an increased IMT in
      the absence of clear-cut abnormalities of the classic vascular risk factors. This
      suggests a role for GH deficiency per se in increasing the atherosclerotic risk.

PMID- 9141520
TI  - Variability of glutathione levels in normal breast tissue and subcutaneous fat
      during the menstrual cycle: an in vivo study with microdialysis technique.
AB  - A small increase in the risk of breast cancer has been reported after long term
      use of combined estrogen-progestagen treatment. Free oxygen radicals and
      antioxidants such as glutathione are involved in the regulation of proliferation
      and apoptosis and thereby in carcinogenesis. To study whether the glutathione
      levels are sex hormone dependent, we used the microdialysis technique to measure
      the in vivo concentrations of glutathione in breast tissue and sc fat during the
      menstrual cycle. Six healthy women (23-32 yr old) were investigated early in the
      follicular phase and the midluteal phase. Two 60-min fractions each were
      collected by microdialysis of periumbilical fat and breast tissue, respectively.
      The samples were stored at -70 C and analyzed by high performance liquid
      chromatography. Glutathione concentrations increased in the midluteal phase
      compared to those in the follicular phase in both adipose tissue and breast
      tissue (P < 0.05). The variability of glutathione levels during the menstrual
      cycle, with higher levels late in the menstrual cycle, indicates that the
      antioxidant system could be sex hormone dependent. This may be of importance in
      breast cancer development.

PMID- 9141521
TI  - Messenger ribonucleic acid expression of heat shock proteins HSP70 and HSP90 in
      human endometrium and myometrium during the menstrual cycle.
AB  - Heat shock proteins of 72 and 90 kDa (HSP70, HSP90) are thought to be involved in
      the functional modulation of sex steroid receptors. To examine the expression and
      transcriptional regulation of HSP70 and HSP90 in both the endometrium and
      myometrium, messenger ribonucleic acid (mRNA) and protein level expression of
      these HSPs during various phases of the menstrual cycle were analyzed by Northern
      blotting and immunohistochemistry. In the endometrium, HSP70 mRNA levels
      increased during the secretory phase compared with levels during the
      proliferative phase; this is consistent with the stronger immunostaining of HSP70
      in glandular cells in the secretory phase. In the myometrium, however, mRNA and
      protein expression of HSP70 were higher in the proliferative phase than in the
      secretory phase. This indicates that the regulatory mechanism of HSP70 expression
      during the menstrual cycle differs between the endometrial glandular cells and
      myometrial smooth muscle cells and may be correlated with the period of sex
      steroid-related functions of the respective cells. Expression of the HSP90 mRNA
      and protein in the myometrium was higher in the proliferative phase than in the
      secretory phase. In the endometrium, HSP90 immunostaining in the glandular cells
      was also stronger in the proliferative phase, although expression of HSP90 mRNA
      was not significantly different between the tissues of the two phases.

PMID- 9141522
TI  - Insulin-like growth factors augment steroid production and expression of
      steroidogenic enzymes in human fetal adrenal cortical cells: implications for
      adrenal androgen regulation.
AB  - The fetal zone is a unique adrenal cortical compartment that exists only during
      fetal life in humans and higher primates and produces large amounts of the
      adrenal androgen dehydroepiandrosterone sulfate (DHEA-S). Growth of the fetal
      zone is primarily regulated by ACTH, the actions of which are mediated in part by
      locally produced autocrine/paracrine growth factors. We previously demonstrated
      that one of these growth factors, insulin-like growth factor II (IGF-II), is
      mitogenic for cultured fetal zone cells and is produced in high abundance by
      these cells in response to ACTH. In the present study, we determined whether IGF
      II also modulates the differentiated function of fetal zone cells. We examined
      the effects of recombinant human IGF-II and the closely related peptide, IGF-I,
      on 1) basal and agonist-stimulated [ACTH-(1-24), forskolin, or 8-bromo-cAMP]
      cortisol and DHEA-S production, 2) basal and ACTH-stimulated steady state
      abundance of messenger ribonucleic acids (mRNAs) encoding the steroidogenic
      enzymes cytochrome P450 side-chain cleavage (P450scc) and cytochrome P450 17alpha
      hydroxylase/17,20-lyase (P450c17), and 3) basal and ACTH-stimulated steady state
      abundance of mRNA encoding the ACTH receptor. Basal cortisol (23.93 +/- 1.20
      pmol/10(5) cells x 24 h) and DHEA-S (548.87 +/- 43.17 pmol/10(5) cells x 24 h)
      productions were significantly (P < 0.05) increased by IGF-I (2.3- and 1.8-fold,
      respectively) and IGF-II (2.8- and 1.8-fold, respectively). As expected, ACTH,
      forskolin, and cAMP markedly increased the production of cortisol by 26-, 10-,
      and 13-fold, respectively, and that of DHEA-S by 5.4-, 4.6-, and 5.5-fold,
      respectively, compared with basal levels. IGF-II (100 ng/mL) significantly (P <
      0.001) increased ACTH-, forskolin-, and cAMP-stimulated production of cortisol by
      2.4-, 4.3-, and 3.2-fold, respectively, and that of DHEA-S by 1.4, 1.6-, and 1.4
      fold, respectively. IGF-I (100 ng/mL) had similar effects as IGF-II and
      significantly (P < 0.001) increased ACTH-, forskolin-, and cAMP-stimulated
      production of cortisol by 2.8-, 3.9-, and 3.1-fold, respectively, and that of
      DHEA-S by 1.3-, 1.6-, and 1.4-fold, respectively. The similar potencies of IGF-I
      and IGF-II suggest that the actions of these factors were mediated via a common
      receptor, most likely the type I IGF receptor. The effects of IGF-II on ACTH
      stimulated steroid production were dose-dependent (EC50, 0.5-1.0 nmol/L), and IGF
      II markedly increased the steroidogenic responsiveness of fetal zone cells to
      ACTH. With respect to cortisol production, IGF-II shifted the ACTH dose-response
      curve to the left by 1 log10 order of magnitude. IGF-II also increased ACTH
      stimulated abundance of mRNA encoding P450scc (1.9-fold) and P450c17 (2.2-fold).
      Basal expression of P450scc was not affected by IGF-II. In contrast, basal
      expression of P450c17 was increased 2.2-fold by IGF-II and IGF-I in a dose
      responsive fashion. Neither IGF-I nor IGF-II affected basal or ACTH-stimulated
      abundance of mRNA encoding the ACTH receptor, suggesting that the increase in
      ACTH responsiveness was not mediated by an increase in ACTH-binding capacity.
      Taken together, these data indicate that activation of the type I IGF receptor
      increases ACTH responsiveness in fetal zone cells by modulating ACTH signal
      transduction at some point distal to ACTH receptor activation. These data also
      indicate that locally produced IGF-II modulates fetal adrenal cortical cell
      function by increasing responsiveness to ACTH and possibly (based on its direct
      stimulation of P450c17 expression) augmenting the potential for adrenal androgen
      synthesis. Thus, activation of the type I IGF receptor on adrenal cortical cells
      may play a pivotal role in adrenal androgen production, both physiologically in
      utero and at adrenarche, and in pathophysiological conditions
      ofhyperandrogenemia, such as the polycystic ovary syndrome.

PMID- 9141523
TI  - Free luteinizing-hormone beta-subunit in normal subjects and patients with
      pituitary adenomas.
AB  - Most clinically nonfunctioning pituitary adenomas (NFPA) are found to be
      gonadotropinomas when assessed by immunocytochemistry. However, they are rarely
      associated with increased basal plasma levels of FSH, LH and/or alpha-subunit. It
      has been claimed that the paradoxical free LHbeta response to TRH may be a useful
      clinical tool for determining the gonadotropic nature of NFPA. We used a very
      specific and sensitive immunoradiometric assay (IRMA) for free LHbeta measurement
      and another specific IRMA to check the absence of free CGbeta, to study normal
      subjects and 26 patients with NFPA. Basal plasma levels of LHbeta were
      undetectable in normal men and premenopausal women in the early follicular phase.
      In contrast, normal postmenopausal women had increased basal plasma LHbeta,
      parallel to dimeric LH and alpha-subunit levels. In healthy subjects, stimulation
      with GnRH elicited an increase in LHbeta while TRH was ineffective. In patients
      with NFPA, LHbeta hypersecretion was found basally and/or after stimulation with
      TRH in 3 of 16 men, 3 of 5 premenopausal women, and 1 of 5 postmenopausal women,
      i.e. 7 of 26 patients (26%). In 3 of these 7 cases, alpha-subunit and/or FSH
      levels were also increased. The LHbeta measurement was thus truly informative on
      the gonadotropic nature of NFPA in only 4 out of 26 cases (15%). In addition,
      increased LHbeta levels and/or a positive response of free LHbeta to TRH was
      observed in 3 patients with pure prolactinomas but in no patients with GH
      secreting adenomas. Thus, using this very sensitive and specific IRMA, free
      LHbeta measurement is rarely helpful for determining the gonadotropic nature of
      NFPA.

PMID- 9141524
TI  - High loading and low maintenance doses of a gonadotropin-releasing hormone
      antagonist effectively suppress serum luteinizing hormone, follicle-stimulating
      hormone, and testosterone in normal men.
AB  - The GnRH antagonist cetrorelix effectively suppresses serum LH, FSH, and
      testosterone (T) in normal men without major side-effects. However, as with other
      available GnRH antagonists, relatively high doses of 10 mg/day were required for
      sustained reduction of T levels during 1-week administration in normal men.
      Therefore, we investigated whether a suppression of LH, FSH, and T achieved by
      initial high dose cetrorelix can be maintained by continued low dose injections.
      Sixteen young male volunteers were randomly assigned to four study groups (n =
      4/group). Twelve men were injected s.c. with 10 mg cetrorelix at 0800 h for 5
      days, followed by injections of 2 mg/day (group I), 2 x 1 mg/day (group II), and
      1 mg/day (group III) up to the end of the 3-week injection period. For the
      control, group IV was given daily placebo injections for 3 weeks. Morning and
      evening blood samples were obtained daily for 4 weeks and then at increasing time
      intervals up to week 13. Initial injections of 10 mg/day cetrorelix suppressed
      LH, FSH, and T effectively. This initial reduction of serum levels was maintained
      during the following low dose maintenance injections in all groups. In comparison
      to the initial suppression, significantly lower levels of LH, FSH, and T near the
      assay detection limits were measured during study weeks 2 and 3. The results show
      that compared to previous long term studies, much lower daily doses of the GnRH
      antagonist are sufficient for effective suppression of LH, FSH, and T after
      initial high loading dose injections. In addition to competitive receptor
      blockage, other mechanisms of GnRH antagonist action, such as receptor down
      regulation, appear to be involved during long term administration in men.

PMID- 9141525
TI  - Production of endometrial matrix metalloproteinases, but not their tissue
      inhibitors, is modulated by progesterone withdrawal in an in vitro model for
      menstruation.
AB  - Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are
      implicated in normal menstruation, but the mechanism of their regulation is not
      yet clear. Human endometrial stromal cell cultures were established to mimic the
      events of the late luteal phase of the menstrual cycle: after 6 days of culture
      with estradiol 17beta (10 nmol/L) and progestin (P, 100 nmol/L), half the cells
      were subjected to P withdrawal, and medium was harvested on day 10.
      Decidualization of the cells was verified by PRL immunohistochemistry. Latent MMP
      1, -2, -3, and -9 were detected by zymography and quantitated by densitometry,
      and production of all enzymes was increased on withdrawal of P. This increase was
      confirmed by enzyme-linked immunosorbent assay for MMP-1. TIMP-1, -2, and -3 also
      were produced by the cells, with a mean ratio of 3.9:1:1.2, respectively. There
      was no effect of P withdrawal on either the amount of each TIMP or their relative
      concentrations. Expression of the messenger RNA for TIMP-1 or TIMP-2 also was not
      changed by P withdrawal. Thus, withdrawal of P alters the ratio of MMPs to TIMPs
      in this model in favor of MMPs and, hence, of tissue degradation. However, the
      focal nature of menstruation-associated MMP activity suggests that P withdrawal
      is unlikely to be the only factor responsible for in vivo induction of MMPs at
      menstruation.

PMID- 9141526
TI  - Loss of heterozygosity at 11q13: analysis of pituitary tumors, lung carcinoids,
      lipomas, and other uncommon tumors in subjects with familial multiple endocrine
      neoplasia type 1.
AB  - Loss of heterozygosity (LOH) for polymorphic markers flanking the multiple
      endocrine neoplasia type 1 (MEN-1) gene in parathyroid and pancreatic islet
      tumors from subjects with familial MEN-1 (FMEN-1) has been well documented and
      has led to the hypothesis that the MEN-1 gene functions as a tumor suppressor. To
      assess the role of the MEN-1 gene in the pathogenesis of tumors less commonly
      associated with MEN-1, we employed a large number of highly informative
      polymorphic markers closely linked to the MEN-1 gene to study a series of 13 such
      tumors from subjects with FMEN-1 for LOH at 11q13. We were able to identify LOH
      for 1 or more 11q13 markers in 2 of 3 pituitary tumors, 3 lung carcinoids, and 1
      of 2 lipomas. In every case studied, the allele lost represented the normal
      allele inherited from the unaffected parent. No LOH was detected in 3 skin
      angiofibromas, an esophageal leiomyoma, or a renal angiomyolipoma despite the
      presence of at least 2 informative markers for each tumor. Our results suggest
      that, like that for parathyroid and pancreatic islet tumors, the pathogenesis of
      pituitary tumors, lung carcinoids, and lipomas occurring in subjects with FMEN-1
      probably involves loss of the normal tumor suppressor function of the MEN-1 gene.
      Our inability to detect 11q13 LOH in skin angiofibromas, leiomyoma, and
      angiomyolipoma from subjects with FMEN-1 is consistent with the possibility that
      these neoplasms arose independently by a mechanism unrelated to the MEN-1 gene,
      but a role for the MEN-1 gene in the pathogenesis of these tumors cannot be
      definitively excluded until the gene itself is identified and evaluated for small
      intragenic deletions or point mutations in such tumors.

PMID- 9141527
TI  - Cellular insulin resistance in adipocytes from obese polycystic ovary syndrome
      subjects involves adenosine modulation of insulin sensitivity.
AB  - Cellular insulin resistance in polycystic ovary syndrome (PCOS) has been shown to
      involve a novel postbinding defect in insulin signal transduction. To find
      possible mechanisms for this defect, adipocytes were isolated from age- and
      weight-matched obese normal cycling (NC) and PCOS subjects. Insulin sensitivity
      for glucose transport stimulation was impaired in PCOS adipocytes (EC50 = 290 +/-
      42 pmol/L) compared to that in NC cells (93 +/- 14; P < 0.005). The lipolytic
      responses to isoproterenol as well as maximal suppression by insulin were similar
      in NC and PCOS adipocytes. However, PCOS cells were less sensitive to the
      antilipolytic effect of insulin (EC50 = 115 +/- 33 pmol/L) compared to NC cells
      (42 +/- 8; P < 0.01). Treatment of adipocytes from NC subjects with the adenosine
      receptor agonist N6-phenylisopropyl adenosine had no effect on either insulin
      responsiveness or sensitivity for glucose transport stimulation. However, N6
      phenylisopropyl adenosine treatment was able to normalize insulin sensitivity in
      PCOS cells (EC50 = 285 +/- 47 vs. 70 +/- 15 pmol/L, before and after treatment; P
      < 0.05). In conclusion, our results suggest that insulin resistance in PCOS, as
      accessed in the adipocyte, occurs at an early step in insulin signaling that is
      common for glucose transport and lipolysis. In addition, this insulin resistance
      involves an impairment of the system by which adenosine acts to modulate insulin
      signal transduction.

PMID- 9141528
TI  - Human Leydig cells and Sertoli cells are producers of interleukins-1 and -6.
AB  - Interleukins (IL)-1 and -6 have been shown to be produced by several categories
      of cells in the rat testis and involved in the paracrine control of testicular
      function. Evidence of high amounts of IL-1 have been shown in the human testis,
      but nothing is known about its cellular origin. Furthermore, to our knowledge,
      the presence of IL-6 in the human testis has not yet been investigated.
      Therefore, the present study was aimed at identifying IL-1 and -6 expression and
      production within the human testis, using RT-PCR, bioassays, and enzyme linked
      immunosorbent assays. We demonstrated that IL-1 and -6 messenger RNA and proteins
      were produced constitutively in vitro by human Leydig cell- and Sertoli cell
      enriched preparations. FSH only stimulated IL-6 production by Sertoli cell
      enriched preparations, but increased the release of both IL-1 and -6 in germ cell
      depleted Sertoli cell cultures. In addition, lipopolysaccharides and latex beads
      enhanced the production of both cytokines by Sertoli cell cultures, whereas human
      chorionic gonadotropin and lipopolysaccharides enhanced the release of both
      cytokines by Leydig cells. Enzyme linked immunosorbent assays and neutralization
      experiments revealed that human Sertoli cells produce essentially the alpha form
      of IL-1, whereas both forms, alpha and beta, are present in Leydig cells. The
      demonstration that human Leydig and Sertoli cells produce IL-1 and -6 under the
      control of gonadotropin hormones and exogenous factors, opens the possibility to
      study the involvement of these cytokines in the control of testis function, in
      normal and pathological conditions in men.

PMID- 9141529
TI  - Lovastatin-induced apoptosis in prostate stromal cells.
AB  - Benign prostatic hyperplasia (BPH) is a common disease of aging men. Current
      medical treatment for this condition is only partially effective, therefore many
      patients must undergo surgery for symptomatic relief. BPH is caused by an
      increase in prostate epithelial and stromal cells, especially the latter. Since
      BPH stromal cells have a long life span and are not very responsive to androgen
      withdrawal, cultured BPH stromal cells were used to explore the feasibility of
      pharmacologically inducing apoptosis in these cells. We obtained BPH tissue
      during surgery, and stromal cells were isolated and maintained in culture. After
      cells achieved confluence, we induced apoptosis with the HMGCoA reductase
      inhibitor, lovastatin (30 micromol/L). The effects of testosterone (100
      micromol/L), dihydrotestosterone (DHT; 100 micromol/L) and finasteride (100
      micromol/L) on lovastatin-induced apoptosis were studied on cells grown in media
      containing charcoal stripped serum. Similarly, we examined the effect of the
      cholesterol pathway metabolites, mevalonic acid (30 micromol/L), geranyl geraniol
      (30 micromol/L), farnesol (10 micromol/L), squalene (30 micromol/L) and 7
      ketocholesterol (3 micromol/L) on lovastatin-induced apoptosis. We demonstrated
      apoptosis by DNA laddering in agarose gels, by fluorescence microscopy following
      acridine orange staining, and by flow cytometry after end-labeling of DNA strand
      breaks with biotin-16-dUTP using deoxynucleotidyl exotransferase (TdT).
      Lovastatin at 30 micromol/L, but not at lower concentrations, induced apoptosis
      in BPH prostate stromal cells. This was seen (by flow cytometry) in 16.6 +/- 7.3%
      (mean +/- SD) of BPH cells treated with lovastatin at 72 h vs. 2.5 +/- 1.2% of
      cells treated with ethanol. Lovastatin-induced apoptosis was not increased in
      stripped serum or by the addition finasteride, and was not inhibited by
      testosterone or DHT. Only mevalonate and geranyl geraniol, prevented lovastatin
      induced apoptosis whereas farnesol, squalene, or 7-ketocholesterol did not. We
      conclude that lovastatin can induce apoptosis in BPH stromal cells in vitro, and
      this is not affected by androgen withdrawal or stimulation. It is unlikely that
      lovastatin, per se, will be an effective treatment for BPH in vivo, but it does
      provide a means for inducing apoptosis in vitro. Understanding the apoptotic
      process in BPH stromal cells ultimately may lead to new therapeutic strategies
      for BPH.

PMID- 9141530
TI  - Steroid 21-hydroxylase autoantibodies: measurements with a new
      immunoprecipitation assay.
AB  - Autoantibodies (Abs) to steroid 21-hydroxylase (21-OH) are a major component of
      adrenal cortex Abs and are characteristic of autoimmune Addison's disease. We
      have developed a new method for measuring Abs to 21-OH based on 125I-labeled
      recombinant human 21-OH produced in yeast. With this assay, 21-OH Abs were
      detected in 43 of 60 (72%) sera from patients with isolated Addison's disease, 11
      of 12 (92%) autoimmune polyglandular syndrome type I sera, 27 of 27 (100%)
      autoimmune polyglandular syndrome type II sera, and 24 of 30 (80%) sera from
      patients who were positive for adrenal cortex antibodies by immunofluorescence
      but had no overt Addison's disease. 21-OH Abs were found by 125I assay in 4 of
      150 (2.7%) sera from patients with insulin-dependent diabetes mellitus, 1 of 77
      (1.3%) Graves' sera, 1 of 67 (1.5%) Hashimoto's sera, and 6 of 243 (2.5%) sera
      from healthy blood donors. 21-OH Abs were not detected in 9 sera from patients
      with Addison's disease due to tuberculosis, 32 sera from patients with noninsulin
      dependent diabetes mellitus, 35 sera from patients with myasthenia gravis, or 17
      sera from patients with premature ovarian failure. There was good agreement
      between the 125I-labeled 21-OH assay and an assay based on 35S-labeled 21-OH
      produced in an in vitro transcription/translation system (r = 0.86; n = 129; P <
      0.001). In the case of sera from patients with Addison's disease, insulin
      dependent diabetes mellitus, Graves' disease, and Hashimoto's disease and from
      healthy blood donors that were low positive in the 125I assay, neutralization
      studies with unlabeled 21-OH confirmed the presence of specific 21-OH Abs.
      Overall, the 21-OH Ab assay based on 125I-labeled 21-OH showed good sensitivity,
      precision, and disease group specificity. This, combined with a simple assay
      protocol and the convenience of 125I handling and counting, make it attractive
      for routine use. Further investigations with the new assay should allow wider
      assessment of the prevalence and pattern of inheritance of adrenal autoimmunity.
      In addition, studies of the effect of treatment or possible preventative measures
      on 21-OH Ab levels in individuals without overt adrenal failure may suggest ways
      of delaying the onset of autoimmune Addison's disease.

PMID- 9141531
TI  - Effects of spontaneous chronic hypoglycemia on central and peripheral nervous
      system in insulinoma patients before and after surgery: a neurophysiological
      follow-up.
AB  - To investigate the effects of spontaneous chronic hypoglycemia on the peripheral
      and central nervous system, a multimodal neurophysiological evaluation [median
      somatosensory (mSEP), brain stem auditory (BAEP), and visual (VEP) evoked
      potentials recordings] was performed in seven insulinoma patients before and 3
      and 6 months after surgical removal of tumor. Before surgery, mSEP findings
      showed abnormal reduction in peripheral wrist-Erb conduction velocity in three
      patients as well as a pathological increase in Erb-N13, N13-N20, and Erb-N20
      conduction times in five cases. BAEP and VEP recordings gave pathological results
      in two patients. Moreover, during hypoglycemia, the III-V and I-V interpeak
      latencies of BAEPs were significantly prolonged (P < 0.01 and P < 0.005,
      respectively) compared to recordings in euglycemia. After 6 months, a mSEP
      recovery, even if partial was noted in four patients, BAEPs were normalized in
      one case, and VEPs were unmodified. Compared to presurgery data, these recordings
      showed a significant (P < 0.05), but incomplete, shortening of BAEPs (III-V and I
      V interpeak latencies) and mSEPs (Erb-N13 and Erb-N20 conduction times). Our
      findings demonstrate that multiple and selective neurophysiological abnormalities
      are present in insulinoma patients, confirm that hypoglycemia impairs suddenly
      brain stem function, and show that after tumor removal, long recovery times for
      improvement of some neurophysiological anomalies are requested.

PMID- 9141532
TI  - Increased levels of serum fibroblast growth factor-2 in diabetic pregnant women
      with retinopathy.
AB  - Fibroblast growth factor-2 (FGF-2) is a potent mitogen and angiogenic factor
      normally absent from the adult circulation. We have previously shown that it
      appears in normal maternal serum and that circulating FGF-2 levels are elevated
      in pregnancies complicated by diabetes. This study was performed to determine
      whether serum FGF-2 is more abundant in pregnant diabetic women with retinopathy
      than in those without. Serum was collected monthly between 14-30 weeks gestation
      and every 2 weeks from then until delivery (35-38 weeks) from 36 women with type
      1 diabetes. FGF-2 was extracted by heparin-Sepharose affinity chromatography and
      quantified by specific RIA. Patients were divided according to the White
      classification of diabetes. In 17 women without retinopathy (White groups B, C,
      and D0), immunoreactive FGF-2 was detectable at 14 weeks (mean +/- SEM, 154 +/-
      39 pmol/L), was maximal after 26 weeks (306 +/- 38 pmol/L), after which values
      steadily declined to term (212 +/- 48 pmol/L). In 19 women with simplex or
      proliferative retinopathy (White groups D+ and R), circulating levels of FGF-2
      were significantly greater between 22-32 weeks gestation (22 weeks, 480 +/- 102
      vs. 239 +/- 38 pmol/L; P < 0.05). Serum FGF-2 was significantly correlated with
      hemoglobin A1c levels at 22, 30, and 34 weeks gestation. The mean birth weight of
      the infants did not significantly differ between groups. Macroalbuminuria was
      absent in all patients, and creatinine clearance and blood pressure did not
      significantly differ between the two groups. The results suggest that serum FGF-2
      is substantially elevated in pregnant diabetic women with retinopathy in second
      and early third trimesters. It is unlikely that in these patients this was
      primarily due to altered FGF-2 clearance, but may relate to excessive production
      by the utero-placental compartment. The high circulating levels of FGF-2 may be
      causally related to the development of diabetic retinopathy.

PMID- 9141533
TI  - The use of tolbutamide-induced hypoglycemia to examine the intraislet role of
      insulin in mediating glucagon release in normal humans.
AB  - Disruption of intraislet mechanisms could account for the impaired glucagon
      response to hypoglycemia in type 1 diabetes. However, in contrast to animals,
      there is conflicting evidence that such mechanisms operate in humans. We have
      used i.v. tolbutamide (T) (1.7 g bolus + 130 mg/h infusion) to create high portal
      insulin concentrations and compared this with equivalent hypoglycemia using an
      i.v. insulin infusion (I) (30 mU/m2 x min). Ten normal subjects underwent two
      hypoglycemic clamps; mean glucose; I (53 +/- 1 mg/dL); and T (53 +/- 1 mg/dL)
      (2.9 +/- 0.04 mmol/L vs. 2.9 +/- 0.05 mmol/L), held for 30 min. During
      hypoglycemia, mean peripheral insulin levels were greater with I (59 +/- 4 mU/L)
      than T (18 +/- 3 mU/L), P < 0.001. Calculated peak portal insulin concentrations
      were greater during T (282 +/- 28 mU/L) than I (78 +/- 4 mU/L), P < 0.00005. The
      demonstration of a reduced glucagon response during T-induced hypoglycemia (111
      +/- 8 ng/L vs. 135 +/- 12 ng/L, P < 0.05) with higher portal insulin
      concentrations suggests that intraislet mechanisms may contribute to the release
      of glucagon during hypoglycemia in man.

PMID- 9141534
TI  - Elderly patients with adult-onset growth hormone deficiency are not osteopenic.
AB  - The age-related decline in GH secretion has been implicated in the development of
      osteoporosis. GH-deficient adults show a significant reduction in bone mineral
      density (BMD), which is greater in those with childhood-onset GH deficiency than
      in those with GH deficiency occurring in adult life. To determine whether GH
      deficiency in late adult life causes a reduction in BMD beyond the decline
      observed with increasing age, we studied 21 patients over the age of 60 yr with
      GH deficiency caused by organic pituitary disease and 23 controls of similar age
      and sex distribution and BMI. Dual energy x-ray absorptiometry was used to
      determine total bone mass and BMD at the hip and in the lumbar spine. Serum
      osteocalcin was determined in all subjects and urinary
      deoxypyridinoline/creatinine ratio in 19 patients and 21 controls. The median
      (range) known duration of GH deficiency in the patients was 8 yr (range, 4-41
      yr). The median (range) total bone mass was 2774 g (range, 1534-3734) in the
      patients and 2717 g (range, 1235-3549) in the controls (P = 0.42). Specific
      measurements of BMD made at L2-L4, the right femoral neck, the right femoral
      trochanter, and Ward's triangle were 1.234 (range, 0.778-1.507) vs. 1.144 g/cm2
      (range, 0.809-1.466; P = 0.48), 0.921 (range, 0.605-1.372) vs. 0.96 g/cm2 (range,
      0.534-1.315; P = 0.62), 0.92 (range, 0.523-1.229) vs. 0.915 g/cm2 (range, 0.353
      1.313; P = 0.68), and 0.773 (range, 0.408-1.289) vs. 0.806 g/cm2 (range, 0.353
      1.154; P = 0.81) in the patients and controls, respectively. The median (range)
      serum osteocalcin was 11.5 (range, 3.6-23.0) vs. 15.1 ng/mL (range, 0.7-40.5; P =
      0.019) in the patients and controls, respectively. The median (range)
      deoxypyridinoline cross-links/creatinine ratio was 3.5 micromol/mol (range, 0.8
      8.3) in the patients and 4.9 micromol/mol (range, 3.0-9.7) in the controls (P
      0.038). There was a significant correlation between serum insulin-like growth
      factor I and total bone mass in the controls, but not in the patients. These data
      demonstrate that BMD is not significantly altered in GH-deficient adults over the
      age of 60 yr. Markers of bone formation and resorption are decreased, however,
      suggesting that bone turnover is reduced. Further studies are required to
      determine whether the reduction in bone turnover in these patients is of benefit.

PMID- 9141535
TI  - In vivo estrogen regulation of epidermal growth factor receptor in human
      endometrium.
AB  - The effects of estrogen and progesterone on the expression of epidermal growth
      factor receptor (EGFR) in human endometrium were studied in hypogonadal women
      under conditions that simulated a normal menstrual cycle. All women received the
      same regimen of estrogen and progesterone and underwent serial biopsies. In one
      group of women (group I), a biopsy was obtained before receiving estrogen (CD0)
      and after 11 days (CD11) of estrogen replacement. A second group of women was
      biopsied on CD11 and CD21 to assess the combined effects of progesterone and
      estrogen (group II). Immunohistochemistry was used to test for the presence of
      EGFR, and a ribonuclease protection assay was used to assess the amounts of EGFR
      messenger ribonucleic acid (RNA) relative to ribosomal RNA in the tissue. In
      group I, a significant increase in EGFR messenger RNA from CD0 to CD11 was
      observed. A similar increase was observed to occur between CD11 and CD21 in group
      II. Immunostaining for EGFR was absent in all CD0 biopsies, but was present in
      all estrogen-exposed endometrium. No difference in immunostaining was noted
      between CD11 and CD21. We conclude that estrogen stimulates the synthesis of EGFR
      in human endometrium and that progesterone does not appear to modulate this
      effect. The examination of other parameters in hormone-replaced hypogonadal
      subjects will be valuable in understanding the complex physiological regulation
      of the human endometrium.

PMID- 9141536
TI  - Endocrine and metabolic effects of long-term administration of [Nle27]growth
      hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women.
AB  - Attenuation of the GH and insulin-like growth factor I (IGF-I) axis in aging may
      be responsible for changes in body composition and metabolism. This relationship
      has been confirmed by studies of recombinant human GH replacement in aging men
      and women, but the adverse effects encountered limit its clinical utility. The
      use of GHRH or its analogs may be an alternative mode for restoring the GH-IGF-I
      axis in aging individuals. Here we report the endocrine-metabolic changes in
      response to a GHRH analog in age-advanced men and women. A single blind,
      randomized, placebo-controlled trial of 5 months duration was conducted. Ten
      women and 9 men between the ages of 55-71 yr self-injected placebo (saline) s.c.
      nightly for 4 weeks followed by 16 weeks of [Nle27]GHRH-(1-29)-NH2 at a dose of
      10 microg/kg. Subjects underwent 12-h nocturnal (2000-0800 h) frequent blood
      sampling (10-min intervals) and 24-h urine collection at baseline, after 4 weeks
      of placebo injections, and after 16 weeks of GHRH analog administration. GH
      responses to GHRH analog and spontaneous GH pulsatility were assessed. Subjects
      were also monitored 2, 4, 8, and 12 weeks after commencement of GHRH analog
      treatment. Blood pressure, body weight, and fasting insulin and glucose levels
      were recorded at each visit. Serum concentrations of IGF-I, IGF binding protein-1
      (IGFBP-1), IGFBP-3, GH-binding protein (GHBP), lipids, and safety laboratory
      tests (complete blood count and chemistry profile) were measured in fasting
      samples (0800-0900 h). Body composition was determined by dual energy x-ray
      absorptiometry scan, and skin thickness was measured at four sites, including the
      right and left hand and volar forearm, by Harpenden skin calipers. Insulin
      sensitivity was assessed by a frequently sampled i.v. glucose tolerance test.
      Quality of life parameters, including sleep, were evaluated through self
      administered questionnaires. Nightly GHRH analog administration at 2100 h
      induced, within 10 min, an acute release of GH, which lasted for 2 h. The GH
      releasing effect of GHRH analog was sustained during the course of the study.
      Compared with placebo, GHRH analog induced a significant increase in 12-h
      integrated nocturnal GH levels in women (P < 0.01) and men (P < 0.05). This was
      accompanied, within 2 weeks, by increased serum levels of IGF-I (P < 0.05) and
      IGFBP-3 (P < 0.001), but not IGFBP-1, which remained elevated for 12 weeks,
      returning toward baseline by 16 weeks in both genders. Within 4 weeks, GHBP
      concentrations were significantly increased (P < 0.01) in women, but not in men.
      Although blood pressure and body weight were unaffected, GHRH analog treatment
      resulted in a significant increase in skin thickness (P < 0.05) in both genders
      and increased lean body mass in men only (P < 0.05), with no other changes in
      body composition or bone mineral density in either gender. There was a trend for
      a positive nitrogen balance in both genders, which became significant (P = 0.03)
      when the data were combined. Fasting insulin and glucose levels were unaltered,
      but a significant increase in insulin sensitivity occurred in men (P < 0.05), but
      not in women. Assessment of quality of life parameters revealed a significant
      improvement in general well-being (P < 0.05) and libido (P < 0.01) in men, but
      not in women, and sleep quality was unaffected in both genders. The only adverse
      side-effect was transient hyperlipidemia, which resolved by the end of the study.
      We conclude that nightly administration of GHRH analog for 4 months in age
      advanced men and women activated the somatotropic axis. Although an increase in
      skin thickness was found in both genders, increases in lean body mass, insulin
      sensitivity, general well-being, and libido occurred in men but not in women.
      These observations suggest that GHRH analog administration induced anabolic
      effects favoring men more than women. Further studies are needed to define the
      gender differences observed in response to GHRH analog administration.

PMID- 9141537
TI  - Levels of leptin in maternal serum, amniotic fluid, and arterial and venous cord
      blood: relation to neonatal and placental weight.
AB  - The mechanisms by which maternal and fetal weight are regulated during pregnancy
      are poorly understood. The ob protein, termed leptin, is produced by adipocytes.
      It is involved in the regulation of body weight by suppressing appetite and
      stimulating energy expenditure both in humans and rodents. In this study we
      examined whether leptin concentrations in the mother and the newborn correlate
      with birth weight, placental weight, and maternal weight at term. Leptin
      concentrations were measured in amniotic fluid, venous and arterial cord blood,
      and maternal serum at birth (n = 27) using a specific RIA employing human
      recombinant leptin for tracer and standard preparation. Gestational age was 38-42
      weeks, maternal age was 21-42 yr, mean maternal weight at birth was 80.0 +/- 10.8
      kg, and mean body mass index before pregnancy was 23.4 +/- 2.8 kg/m2. The
      newborns' mean weight was 3450 +/- 580 g, and mean placental weight was 616 +/-
      120 g. Serum leptin levels from nonpregnant women ranged between 1.7-18.4 ng/mL,
      median 5.5 ng/ml (n = 30). Mean leptin concentration in maternal serum at birth
      was 20.0 +/- 13.2 ng/mL and was higher (P < 0.002) than in arterial cord blood
      (9.7 +/- 9.4 ng/mL) and venous cord blood (8.9 +/- 8.6 ng/mL). Mean amniotic
      fluid leptin concentration was 3.6 +/- 2.8 ng/mL. Placental weight correlated
      inversely with leptin levels in maternal serum at birth (r = -0.49, P < 0.01). In
      addition, leptin concentrations in venous cord blood correlated significantly
      with the levels in arterial cord blood (r = 0.98, P < 0.0001), and leptin levels
      in cord blood correlated positively with birth weight (r = 0.57, P = 0.03) and
      placental weight (r = 0.50, P < 0.01). In contrast, there was no correlation
      between maternal serum leptin levels and birth weight. Thus, leptin levels are
      high in the fetus and in the mother at term. We hypothesize that high leptin
      levels could represent an important feed-back modulator of substrate supply and
      subsequently for adipose tissue status during late gestation.

PMID- 9141538
TI  - Circulating levels of insulin-like growth factor (IGF) binding protein-1 and -3
      in aging men: relationships to insulin, glucose, IGF, and dehydroepiandrosterone
      sulfate levels and anthropometric measures.
AB  - Reduced secretion of GH and production of insulin-like growth factor I (IGF-I)
      contribute to altered body composition in human aging. IGF-binding proteins
      (IGFBPs) are important modulators of IGF action, yet little is known regarding
      their role and regulation in aging. Accordingly, we measured levels of IGFBP-1,
      an important short term modulator of IGF bioavailability that is suppressed by
      insulin, and levels of IGFBP-3, the major circulating IGF carrier protein, and
      examined their relationships to insulin, glucose, IGF, and dehydroepiandrosterone
      sulfate levels and anthropometric measures in old (63-89 yr) and young (23-39 yr)
      men. Serum levels of IGFBP-1 were increased 3-fold in old vs. young men despite
      high insulin levels in elders. Nevertheless, IGFBP-1 and insulin levels
      correlated in old and young men (r = - 0.49; P < 0.002 and r = -0.42; P < 0.025),
      suggesting that insulin continues to play an important role in the regulation of
      IGFBP-1 in aging. Glucose levels also were significantly inversely related to
      IGFBP-1 in old and young men (r = 0.37; P = 0.02 and r = -0.49; P < 0.01), and
      this relationship was not accounted for by the effect of insulin. IGF-I levels
      were reduced by 33% in elders (P < 0.001) and correlated with IGFBP-1 levels
      among old (r = -0.40; P < 0.01), but not young, men, indicating that low GH
      secretion and/or IGF-I production may contribute to the elevation of IGFBP-1
      levels in aging. IGFBP-3 levels were reduced among elders, but not to the same
      extent as IGF-I, resulting in a relative excess of IGFBP-3 in elders (IGFBP-3/IGF
      I ratio, 20.1 +/- 0.9 vs. 15.4 +/- 1.0; P < 0.001). The IGFBP-3/IGF-I ratio
      correlated with IGF-I levels in young and old men (r = -0.79; P < 0.001 and r = 
      0.82; P < 0.001), indicating that diminished GH secretion also may contribute to
      a relative excess of IGFBP-3 among elders. Dehydroepiandrosterone sulfate levels
      were low in elders, but did not correlate with IGF, IGFBP, insulin, or glucose
      levels in either age group. Serum levels of IGFBP-1 (but not IGF-I or -II or
      IGFBP-3) correlated with body mass index and upper arm fat and muscle areas in
      elders. These relationships were accounted for by the effects of insulin,
      suggesting that regulation of IGFBP-1 by insulin may play a role in determining
      body composition in aging. We conclude that insulin remains an important
      determinant of IGFBP-1 levels in elders, that the fasting glucose level is also a
      significant determinant of IGFBP-1 in both old and young subjects, and that
      reduced secretion of GH may contribute to impaired anabolism in aging through
      multiple mechanisms, including reduced production of IGF-I and alterations in
      circulating levels of both IGFBP-1 and -3. These findings are consistent with the
      concept that alterations in IGFBP levels may contribute to changes in IGF
      bioavailability and body composition in aging.

PMID- 9141539
TI  - Determination of testosterone production rates in men and women using stable
      isotope/dilution and mass spectrometry.
AB  - Production rates of testosterone were determined in healthy men and women during
      the follicular phase of their menstrual cycle using the stable isotope dilution
      technique and analysis by gas chromatography/mass spectrometry. In an initial
      series of experiments, 0.07 mg/h (men) or 0.01 mg/h (women) 1,2-d-testosterone
      was infused for 36 h. After an equilibration period of 12 h, blood samples were
      obtained at 20-min intervals throughout 24 h. In men, no diurnal rhythmicity of
      testosterone production was observed, whereas in women, testosterone production
      rates were largest from 0400-1200 h. In a second series of experiments, the
      infused dose of 1,2-d-testosterone was reduced to 0.015 mg/h (men) and 0.0001
      mg/h (women), respectively. Blood samples were obtained at 20-min intervals
      during the last 12 h (0800-2000 h) of the observation period. In accordance with
      results obtained by others using radioactive tracers, estimated production rates
      were 147 +/- 31 microg/h (3.7 +/- 2.2 mg/day in men) and 1.8 +/- 0.6 microg/h
      (0.04 +/- 0.01 [corrected] mg/day in women). To reduce both the duration of the
      experiment and the number of samples to be processed, we subsequently
      demonstrated that similar production rates may be obtained when the equilibration
      period before blood sampling is reduced to 6 h and the period of blood sampling
      is reduced to 4 h. This protocol is suitable for clinical use in a routine
      setting to obtain analytically correct estimates of testosterone production in
      vivo.

PMID- 9141540
TI  - Bone loss and turnover after cardiac transplantation.
AB  - Cardiac transplantation is associated with increased prevalence and incidence of
      fracture, and rapid bone loss has been reported during the first posttransplant
      year. To define further the pattern and etiology of bone loss after cardiac
      transplantation, we enrolled 70 patients (52 men and 18 women) in a prospective 3
      yr study. Bone densitometry (BMD) and biochemical indexes of mineral metabolism
      were performed before and at defined times after transplantation. Despite
      supplementation with elemental calcium (1000 mg/day) and vitamin D (400 IU/day),
      the mean rate of bone loss during the first year was 7.3 +/- 0.9% (+/- SEM) at
      the lumbar spine and 10.5 +/- 1.1% at the femoral neck. The rate of bone loss
      slowed (P < 0.001 compared to year 1) at both sites (0.9 +/- 0.9% and 0.1 +/-
      1.0%, respectively) during the second year. During the third year, lumbar spine
      BMD increased at a rate of 2.4 +/- 0.8%/yr (P < 0.02 compared to year 2), but
      femoral neck BMD did not change. At the radius, the rate of decline in BMD was
      negligible during the first year (0.9 +/- 0.5%), but was significant during the
      second (2.1 +/- 0.6%; P < 0.01) and third (2.9 +/- 0.8%; P < 0.03) years.
      Evaluation of the pattern of bone loss during the first year demonstrated that
      mean lumbar spine BMD decreased rapidly during the first 6 months, after which
      there was no further decline. In contrast, femoral neck BMD continued to fall at
      an annualized rate of 8.2 +/- 1.3% during the second half of the year. The
      pattern and rates of bone loss were similar in men and women. Biochemistries
      revealed decreases in serum testosterone and osteocalcin and increases in all
      bone resorption markers 1 and 3 months after transplantation, with a return to
      baseline by 6 months. Higher rates of bone loss were associated with greater
      exposure to prednisone, lower serum concentrations of vitamin D metabolites,
      greater suppression of osteocalcin, higher levels of bone resorption markers,
      and, in men, lower serum testosterone concentrations. We conclude that rapid bone
      loss is primarily confined to the initial year after transplantation. During the
      first 6 months, bone loss is accompanied by alterations in markers of bone
      turnover consistent with biochemical uncoupling of bone formation and resorption.
      Greater exposure to glucocorticoids, lower serum concentrations of vitamin D
      metabolites and testosterone, and higher bone turnover were associated with more
      rapid bone loss.

PMID- 9141541
TI  - Impaired potassium-stimulated aldosterone production: a possible explanation for
      normokalemic glucocorticoid-remediable aldosteronism.
AB  - Unlike other forms of primary aldosteronism, recent prospective studies have
      paradoxically revealed that glucocorticoid-remediable aldosteronism (GRA) is
      usually characterized by normal potassium (K+) levels. To evaluate this paradox
      we studied 10 GRA subjects and 14 healthy controls in two protocols: 1) the renal
      K+ excretory response to acute oral administration of 50 mmol K+ chloride and to
      fludrocortisone, 0.2 mg p.o. q12 h x 4 doses; and 2) the aldosterone response to
      administration of 50 mmol K+ chloride. The K+ excretion rate (KER) in GRA
      subjects (n = 6) at baseline (45.6 +/- 8.3 microEq/min), after K+ (134 +/- 34.2
      microEq/min), and after fludrocortisone (100 +/- 35.0 microEq/min) was not
      significantly different than that seen in the control (n = 8) subjects (54.9 +/-
      19.0, 154 +/- 35.5, 112 +/- 45.8 microEq/min, respectively). Thus the renal
      kaliuretic response to K+ ingestion and exogenous mineralocorticoid is normal in
      GRA. Serum aldosterone increased from 5.0 +/- 3.8 at baseline to a maximum of
      13.1 +/- 6.6 ng/dL 60 min after K+ ingestion in control subjects (n = 7), but
      failed to increase in GRA subjects (n = 14), going from 8.7 +/- 3.8 (baseline) to
      8.8 +/- 5.4 ng/dL at 60 min (P = 0.004 vs. control). The blunted aldosterone
      response to K+ in GRA in association with the sharp diurnal decline in
      aldosterone in this ACTH-regulated syndrome probably results in a milder degree
      of hyperaldosteronism compared with other forms of primary aldosteronism, thereby
      producing volume expansion with minimal renal K+ wasting.

PMID- 9141542
TI  - Spontaneous feminization in a 46,XX female patient with congenital lipoid adrenal
      hyperplasia due to a homozygous frameshift mutation in the steroidogenic acute
      regulatory protein.
AB  - The most severe form of congenital adrenal hyperplasia (CAH) is lipoid CAH. It
      was once thought that this disease was due to mutations in the cholesterol side
      chain cleavage enzyme system, thus eliminating the ability to convert cholesterol
      to pregnenolone, causing a complete absence of steroid hormone production. We
      recently showed that lipoid CAH is due to mutations in the steroidogenic acute
      regulatory (StAR) protein, thus preventing acutely stimulated adrenal and gonadal
      responses to tropic stimulation. However, this lesion may permit low levels of
      StAR-independent steroidogenesis to persist until the accumulation of
      intracellular lipid deposits destroys steroidogenic capacity. This model would
      predict that the steroidogenic cells of the ovaries of affected 46,XX females
      should remain undamaged until puberty, at which time low levels of StAR
      independent estrogen biosynthesis should be detectable. We describe a 15.5-yr-old
      46,XX female with a classic history of lipoid CAH who underwent spontaneous
      feminization and cyclical vaginal bleeding beginning at age 13. Genetic analysis
      of the patient and her parents showed that she was homozygous for the novel StAR
      frameshift mutation 261delT. This is the first adolescent female with lipoid CAH
      who has undergone spontaneous feminization and who has been analyzed genetically.
      Finding an inactive StAR gene in this patient confirms our two-hit model of the
      pathogenesis of lipoid CAH, in which loss of StAR activity initially preserves
      StAR-independent steroidogenesis, which is lost only after cells undergo chronic
      tropic stimulation and subsequent damage from accumulation of cholesterol esters.

PMID- 9141543
TI  - Circulating non-22-kilodalton growth hormone isoforms in acromegalic men before
      and after transsphenoidal surgery.
AB  - GH represents several molecular isoforms in addition to the main 22-kDa (22K) GH.
      There have been reports suggesting that circulating non-22K GH isoforms are
      increased in acromegaly, but the possible implications of such observations in
      the management of the disease have not been addressed. The aim of this study was
      to evaluate the proportion of circulating non-22K GH isoforms in acromegaly. In
      addition, the relationships between the amount of non-22K GH and tumor size,
      biochemical measurements, and body composition also were investigated. Samples
      with different GH levels were selected from 24-h GH profiles from 15 acromegalic
      men evaluated before and 1 yr after transsphenoidal surgery and from 13 healthy
      men. The serum non-22K GH levels, expressed as percentage of total GH
      concentration, were determined by the 22K GH exclusion assay, which is based on
      immunomagnetic extraction of 22K GH from serum and quantitation of non-22K GH
      using a polyclonal GH assay. The proportion of non-22K GH isoforms was fairly
      constant in different samples from the same patient, regardless of the GH level.
      However, a wide variation of values was observed among acromegalics, both before
      (14-51%) and after surgery (8-62%). The proportion of non-22K GH isoforms was
      increased in untreated patients, compared with controls (26.6 vs. 17.4%; P <
      0.01), and the values correlated significantly to tumor size, mean 24-h GH
      concentration, serum PRL, and extracellular water. After surgery, patients not
      truly cured, with mean 24-h GH concentration of 1 microg/L or more, had an
      increased proportion of non-22K GH, compared with those with levels less than 1
      microg/L (P < 0.01). In the former group, the median values were similar than
      those in untreated acromegalics (34 vs. 26.6%, respectively), whereas in the
      latter, they were comparable with those in the controls (15.2 vs. 17.4%,
      respectively). We conclude that acromegalics have an increased proportion of
      circulating non-22K GH isoforms. The values are fairly constant in different
      samples from an individual, regardless of GH level, but a large spectrum can be
      observed among patients. This variability suggests that different pituitary
      adenomas secrete GH isoforms in variable amounts. Our observation that a higher
      proportion of non-22K GH isoforms is present in patients not truly cured after
      surgery suggests that the evaluation of non-22K GH isoforms can be useful in the
      follow-up of acromegalic patients.

PMID- 9141544
TI  - Effects of age and estrogen status on serum parathyroid hormone levels and
      biochemical markers of bone turnover in women: a population-based study.
AB  - Although estrogen deficiency is responsible for the increase in bone turnover in
      early postmenopausal women, age-related factors, such as the progressive increase
      in serum PTH levels, are believed to be responsible for the increase in bone
      turnover in elderly women. Whether estrogen deficiency continues to play a role,
      either directly or indirectly, in the pathogenesis of the increased bone turnover
      in elderly women remains unclear. Thus, we measured serum PTH, markers of bone
      turnover, and serum sex steroid levels in a population-based sample of 351 women
      (age range, 21-94 yr), which included 47 postmenopausal women who were receiving
      long term estrogen replacement therapy. Serum PTH increased as a function of age
      when the premenopausal women and the estrogen-deficient postmenopausal women were
      analyzed together (r = 0.35; P < 0.001). By contrast, this age-related increase
      in serum PTH was eliminated in the postmenopausal women receiving long term
      estrogen therapy, which also resulted in a similar suppression of markers of bone
      formation and resorption in both the early (< or = 20 yr) and late (> 20 yr)
      postmenopausal women. By multivariate analysis, serum 25-hydroxyvitamin D levels
      were highly predictive of serum PTH levels regardless of menopausal status,
      whereas serum estrone levels were predictive of markers of bone resorption in the
      postmenopausal women. We conclude that estrogen deficiency may be responsible not
      only for the increase in bone turnover in early postmenopausal women, but also
      indirectly for the secondary hyperparathyroidism and increase in bone turnover
      found in late postmenopausal women. Residual serum estrogen levels are important
      determinants of bone resorption in postmenopausal women.

PMID- 9141545
TI  - Androstane-3alpha,17beta-diol glucuronide as a steroid correlate of visceral
      obesity in men.
AB  - Plasma levels of androstane-3alpha,17beta-diol glucuronide (3alpha-DIOL-G) and
      androsterone glucuronide (ADT-G) as well as testosterone and adrenal C19 steroid
      concentrations were measured in a sample of 80 men in whom visceral adipose
      tissue (AT) accumulation was also determined by computed tomography. Plasma
      3alpha-DIOL-G concentrations showed significant positive correlations with total
      body fat mass (r = 0.31; P < 0.05) and percent body fat (r = 0.28; P < 0.05).
      Furthermore, plasma 3alpha-DIOL-G levels were significantly associated with
      visceral adipose tissue accumulation (r = 0.41; P < 0.0005) as well as fasting
      plasma insulin (r = 0.35; P < 0.005) and glycemic and insulinemic responses to an
      oral glucose load (r = 0.39; P < 0.0005 and r = 0.32; P < 0.005, respectively).
      However, associations between 3alpha-DIOL-G and plasma glucose-insulin
      homeostasis indexes were no longer significant after adjustment for visceral AT
      area. ADT-G levels were not significantly associated with any of the adiposity
      variables. Subjects matched for abdominal sc AT area but with either low or high
      levels of visceral AT area showed significant differences in 3alpha-DIOL-G
      concentrations (P < 0.05), whereas subjects with low or high levels of abdominal
      sc AT but similar levels of visceral AT had similar 3alpha-DIOL-G concentrations.
      Among men with high testosterone levels, subjects with reduced 3alpha-DIOL-G
      concentrations had lower visceral adipose tissue accumulation than subjects with
      increased 3alpha-DIOL-G levels. The present results indicate that plasma 3alpha
      DIOL-G, but not ADT-G, is a steroid correlate of visceral obesity. Excess
      visceral adipose tissue and/or concomitant alterations in insulin levels or in
      vivo insulin action could be responsible for the increased 3alpha-DIOL-G
      formation observed in this condition.

PMID- 9141546
TI  - Elevated 3,5-diiodothyronine concentrations in the sera of patients with
      nonthyroidal illnesses and brain tumors.
AB  - This study reports the development of a highly sensitive and reproducible RIA for
      the measurement of 3,5-diiodothyronine (3,5-T2) in human serum and tissue. The
      RIA employs 3-bromo-5-[125I]iodo-L-thyronine (3-Br-5-[125I]T1) as tracer, which
      was synthesized carrier free by an interhalogen exchange from 3,5-dibromo-L
      thyronine (3,5-Br2T0). The detection limits were 1.0 fmol/g and 0.8 pmol/L in
      human brain tissue and serum, respectively. T3, diiodothyroacetic acid, and 3
      monoiodothyronine cross-reacted with a 3,5-T2 antibody to the extent of 0.06%,
      0.13%, and 0.65%, respectively. Serum concentrations of 3,5-T2 were measured in
      62 healthy controls and 4 groups of patients with nonthyroidal illness, i.e.
      patients with sepsis (n = 24), liver diseases (n = 23), head and/or brain injury
      n = 15), and brain tumors (n = 21). The mean serum level of 3,5-T2 in the healthy
      subjects was 16.2 +/- 6.4 pmol/L. Concentrations of 3,5-T2 were significantly
      elevated in patients with sepsis (46.7 +/- 48.8 pmol/L; P < 0.01), liver diseases
      (24.8 +/- 14.9 pmol/L; P < 0.01), head and/or brain injury (24.1 +/- 11.3 pmol/L;
      P < 0.05), and brain tumors (21.6 +/- 4.8 pmol/L; P < 0.01). In all 4 patient
      groups, serum levels of T3 were significantly reduced, confirming the existence
      of a low T3 syndrome in these diseases. Serum concentrations of 3,5-T2 were
      significantly elevated in patients with hyperthyroidism (n = 9) and were reduced
      in patients with hypothyroidism (n = 8). The levels of T4, T3, and 3,5-T2 were
      measured in normal human tissue samples from the pituitary gland and various
      brain regions and in brain tumors. In normal brain tissue, the concentrations of
      3,5-T2 ranged between 70-150 fmol/g, and the ratio of T3 to 3,5-T2 was
      approximately 20:1. In brain tumors, however, T3 levels were markedly lower,
      resulting in a ratio of T3 to 3,5-T2 of approximately 1:1. Recent findings
      suggest a physiological, thyromimetic role of 3,5-T2, possibly stimulating
      mitochondrial respiratory chain activity. Should this prove to be correct, then
      the increased availability of 3,5-T2 in nonthyroidal illness may be one factor
      involved in maintaining clinical euthyroidism in patients with reduced serum
      levels of T3 during nonthyroidal illness.

PMID- 9141547
TI  - Pulsatile intravenous gonadotropin-releasing hormone administration averts
      fasting-induced hypogonadotropism and hypoandrogenemia in healthy, normal weight
      men.
AB  - Fasting or severe caloric restriction in the human or experimental animal
      suppresses serum LH and sex steroid concentrations. In healthy men undergoing
      prolonged (5-day) nutrient deprivation, the daily LH secretion rate, the mass of
      LH secreted per burst, and the serum testosterone concentration fall markedly,
      with no decrease in responsiveness to a single bolus of GnRH. Here we test the
      hypothesis that the hypogonadotropic hypoandrogenemia accompanying fasting
      reflects decreased endogenous GnRH release. To this end, six healthy young men
      were studied on a fed day and during two 83-h fasting sessions with concurrent
      saline or pulsatile GnRH administration (100 ng/kg, i.v., every 90 min for 24 h)
      followed by a single bolus of 10 microg GnRH, i.v., to evaluate pituitary
      responsiveness. We employed a highly sensitive LH immunoradiometric assay, which
      correlates well with an in vitro Leydig cell bioassay, and deconvolution analysis
      to calculate in vivo LH secretory burst frequency, amplitude, duration, mass, and
      LH half-life. Fasting resulted in 30-50% declines in serum total and free
      testosterone and LH concentrations, and a 3-fold decrease in the calculated 24-h
      LH secretion rate (fed, 42 +/- 12; fasting, 14 +/- 1.9 U/L distribution volume x
      day; mean +/- SEM; P < 0.05, by ANOVA). Reduced LH secretion was accounted for by
      dual mechanisms, viz. a fall in both the apparent number of computer-resolved LH
      secretory bursts per 24 h (fed, 16 +/- 1.1; fasting, 10 +/- 1.2; P < 0.01) and
      the mass of LH secreted per burst (fed, 2.5 +/- 0.5; fasting, 1.5 +/- 0.1 U/L; P
      < 0.05). Fasting also decreased the mean value of the 24-h (nyctohemeral) rhythm
      in serum LH concentrations and reduced the approximate entropy (disorderliness)
      of LH release. Exogenous pulsatile GnRH injections prevented both the reduction
      in the calculated daily LH secretion rate (fed, 42 +/- 12; fasting plus GnRH, 64
      +/- 16 IU/L; P = NS) and the decline in serum testosterone concentrations (fed,
      556 +/- 71 ng/dL; fasting, 391 +/- 41; fasting plus GnRH, 859 +/- 65). Pulsatile
      GnRH treatment also restored the nyctohemeral mesor of serum LH concentrations
      and the approximate entropy value to baseline. Administration of a submaximal
      dose of exogenous GnRH (10 microg, i.v.) at the end of the fasting interval
      revealed statistically identical LH release in the three study groups, suggesting
      that pituitary responsiveness to GnRH was unchanged in this paradigm. In summary,
      a pulsatile iv GnRH infusion in young men averts completely the fasting-induced
      decline in LH secretory burst mass/amplitude and frequency, reinstates serum
      total and free testosterone concentrations, and restores the mesor of LH's
      nyctohemeral rhythmicity and the approximate entropy of LH release. Rescue of
      hypogonadism by pulsatile GnRH stimuli supports the thesis that nutrient
      withdrawal decreases the output of the human hypothalamic GnRH burst generator.

PMID- 9141548
TI  - Effect of postmenopausal hormone therapy on body weight and waist and hip girths.
      Postmenopausal Estrogen-Progestin Interventions Study Investigators.
AB  - Reports from cross-sectional comparisons, nonrandomized prospective studies, and
      relatively small clinical trials indicate that postmenopausal hormone therapy may
      slightly decrease the amount of weight typically gained by women during the
      decade following menopause. Despite this, widespread belief remains that hormone
      therapy may cause weight gain. We use data from the Postmenopausal
      Estrogen/Progestin Interventions trial to characterize the impact of
      postmenopausal hormone therapy on weight and fat distribution and to examine the
      consistency of this impact among subgroups of women defined by lifestyle,
      clinical, and demographic factors. The Postmenopausal Estrogen/Progestin
      Interventions trial was a 3-yr, placebo-controlled, randomized clinical trial of
      875 women assessing the effects on cardiovascular risk factors of four hormone
      regimens: oral conjugated equine estrogen (CEE) therapy (0.625 mg daily alone),
      CEE in combination with medroxyprogesterone acetate (2.5 mg daily), CEE in
      combination with medroxyprogesterone acetate (10 mg daily on days 1-12), and CEE
      in combination with micronized progesterone (200 mg daily on days 1-12). Women
      randomly assigned to CEE with or without a progestational agent averaged 1.0 kg
      less weight gain at the end of 3 yr (P = 0.006) than those assigned to placebo.
      Assignment to CEE was also associated with averages of 1.2 cm less increase in
      waist girth (P = 0.01) and 0.3 cm less increase in hip (P = 0.07) girth. In
      regression models that included weight change as a covariate, none of these
      differences reached statistical significance. There were no significant
      differences in weight or girth changes among any of the four active hormone
      regimens. After accounting for the effects of assignment to active hormone
      therapy and baseline weight, older age (P 0.008) and higher physical activity
      level at baseline (P = 0.002) were also independently predictive of less weight
      gain. The impact of hormone therapy on weight gain was similar among subgroups,
      except for those defined by baseline smoking status (P = 0.04) and physical
      activity level at home (P = 0.02). Factors that were independently associated
      with smaller increases in girths were: for waist, greater overall activity (P =
      0.005) and Hispanic ethnicity (P = 0.02); and for hip, work activity (P = 0.003)
      and greater alcohol consumption (P = 0.03). None of these factors significantly
      affected the observed overall relationships between estrogen and changes in
      girth.

PMID- 9141549
TI  - Inhibin A and activin A in the first trimester of human pregnancy.
AB  - Recent studies show that high concentrations of inhibin A and activin A are
      present in the maternal serum throughout human pregnancy. The aim of this study
      was to determine whether the corpus luteum produces significant quantities of
      inhibin A and activin A during the first trimester of pregnancy. This prospective
      study examined two groups of women who had blood samples taken from 5-12 weeks
      gestation. One group consisted of 14 women with donor egg pregnancies (8
      singletons and 6 multiples) who did not have corpora lutea, and the other group
      consisted 5 women with spontaneous pregnancies who had corpora lutea. Inhibin A
      and activin A were measured at weekly intervals using specific enzyme
      immunoassays. All pregnancies progressed to term, with healthy babies being
      delivered. Maternal serum concentrations of inhibin A significantly increased
      throughout the study period in the donor egg pregnancies (P < 0.001) and the
      control pregnancies (P < 0.001). Circulating concentrations of activin A also
      increased significantly in both the spontaneous and donor egg pregnancies (P <
      0.001) during the study period. However, the concentrations of inhibin A and
      activin A in the first trimester of human pregnancy were not significantly
      different in the women with or without corpora lutea, suggesting a fetoplacental
      origin. Multiple donor egg pregnancies were found to have higher concentrations
      of inhibin A (P < 0.001) and activin A (P < 0.05) compared with singleton donor
      egg pregnancies, which also supports a placental source.

PMID- 9141550
TI  - A novel mechanism for isolated central hypothyroidism: inactivating mutations in
      the thyrotropin-releasing hormone receptor gene.
AB  - Isolated central hypothyroidism, characterized by insufficient TSH secretion
      resulting in low levels of thyroid hormones, is a rare disorder. We report a boy
      in whom isolated central hypothyroidism was diagnosed at 9 yr of age. Complete
      absence of TSH and PRL responses to TRH led us to speculate that he had an
      inactivating mutation of the TRH receptor gene. The patients' genomic DNA was
      isolated, and the entire coding region of the TRH receptor was amplified by the
      PCR and sequenced directly. Confirmation of the mutations and haplotyping of the
      family was performed using restriction enzymes. The biological activity of the
      wild-type and mutated TRH receptors was verified by evaluating the binding of
      labeled TRH and stimulation by TRH of total inositol phosphate accumulation in
      transfected HEK-293 and COS-1 cells. The patient was found to be a compound
      heterozygote, having inherited a different mutated allele from each of the
      parents; both mutations were in the 5'-part of the gene. Mutated receptors were
      unable to bind TRH and to activate total inositol phosphate accumulation. Our
      report is the first description of naturally occurring inactivating mutations of
      a G protein-coupled receptor linked to the phospholipase C second messenger
      pathway. The prevalence and phenotypic spectrum of TRH receptor mutations in
      isolated central hypothyroidism remain to be established.

PMID- 9141551
TI  - Heterogeneity of the human corticotropin-releasing factor-binding protein.
AB  - Human corticotropin-releasing factor (hCRF), secreted by the placenta,
      principally in the third trimester, is specifically bound in the peripheral
      circulation to a 37-kDa binding protein (CRF-BP). This complex is cleared from
      the circulation. We postulate that the protein may be returned to the blood in a
      form that is immunologically altered and not well recognized by the reported
      RIAs. We report that a stable isoform can result from temporary denaturation of
      recombinant CRF-BP by 8 mol/L urea. This isoform, urea-treated binding protein,
      which can bind CRF, has been found to bind to an antibody raised against a
      synthetic peptide comprising the first 24 amino acid residues of CRF-BP, but not
      to a second similar N-terminal antibody, although it was closely matched in
      titer. Urea-treated binding protein also cross-reacts poorly in the RIA with CRF
      BP. It is proposed that as a result of in vivo post-ligand binding events,
      isoforms may be susceptible to cleavage. After affinity purification, which
      involves denaturation, recombinant CRF-BP was often found to be cleaved after
      storage in the presence of protease inhibitors. Here we present evidence for a C
      terminally truncated form of the native binding protein in the plasma of subjects
      suffering from rheumatoid arthritis, which may parallel the in vitro truncation.

PMID- 9141552
TI  - Acute dyslipoproteinemia induced by interleukin-2: lecithin:cholesteryl
      acyltransferase, lipoprotein lipase, and hepatic lipase deficiencies.
AB  - Recombinant human interleukin-2 (rIL-2) is used to treat refractory cancers.
      During such treatment, patients develop severe hypocholesterolemia along with
      striking alterations in the concentration and composition of the circulating
      lipoproteins. The present study was undertaken to gather information about the
      pathogenesis of these abnormalities. Patients were studied before-, during- and
      after a 5-day course of high dose i.v. rIL-2. Whole plasma cholesterol was
      markedly reduced by rIL-2 administration (52%; P < 0.001), whereas the
      triglyceride concentration did not change. Thus, the lipoproteins became
      triglyceride enriched (P = 0.004). Low density lipoprotein cholesterol,
      apolipoprotein B (apoB), high density lipoprotein cholesterol, and apoA-I
      concentrations all decreased. Esterified cholesterol levels were markedly
      reduced. Total plasma apoE increased markedly, and two kinds of abnormal
      particles appeared: 1) beta-migrating, very low density lipoproteins; and 2)
      discoidal, apoE- and phospholipid-containing particles with abnormal density and
      electrophoretic mobility. The activities of two lipoprotein triglyceride
      hydrolases, lipoprotein lipase and hepatic lipase, fell significantly during
      treatment and returned promptly to pretreatment levels after rIL-2 was
      discontinued. Lecithin:cholesteryl acyltransferase (LCAT) activity also decreased
      significantly (64%) during treatment, but in contrast to the lipases, remained
      low for at least 5 days after the last dose of rIL-2 (P < 0.001). High dose i.v.
      rIL-2 induces severe dyslipidemia with deficiencies of both postheparin lipases
      and acute LCAT deficiency. Most, if not all, of the lipoprotein changes observed
      are explained by the LCAT deficiency that follows IL-2-induced hepatocellular
      injury and cholestasis.

PMID- 9141553
TI  - Hypoxia stimulates cytokine production by villous explants from the human
      placenta.
AB  - It has been hypothesized that inadequate placentation in the hypertensive
      disorder of pregnancy known as preeclampsia creates foci of placental
      ischemia/hypoxia leading to the elaboration of factors that compromise systemic
      endothelial function to produce disease sequelae. As tumor necrosis factor-alpha
      (TNF alpha) and interleukin-1 (IL-1) are inflammatory cytokines capable of
      eliciting endothelial cell dysfunction, we investigated whether the production of
      these inflammatory cytokines by cultured villous explants from the human placenta
      was affected by incubation in reduced oxygen (2% O2). The term placenta produced
      TNF alpha, IL-6, and low levels of IL-1alpha and IL-1beta under standard tissue
      culture conditions. Hypoxia significantly increased TNF alpha, IL-1alpha, and IL
      1beta production by 2-, 6-, and 23-fold, respectively, but did not affect IL-6
      production. Further, cytokines were immunolocalized to the syncytiotrophoblast
      layer as well as to some villous core cells. Hypoxic regulation of placental TNF
      alpha and IL-1beta production also appeared to differ based on gestational age.
      Finally, treatment with either cobalt chloride or an iron chelator mimicked the
      hypoxic response, suggesting that stimulation of placental cytokine production
      may involve a heme-containing, O2-sensing protein. These results suggest that
      placental hypoxia can lead to the elaboration of inflammatory cytokines, which
      may contribute to the pathophysiology of preeclampsia.

PMID- 9141554
TI  - Routine measurement of plasma calcitonin in nodular thyroid diseases.
AB  - In a prospective study, plasma concentrations of human calcitonin (hCT) were
      determined in 1062 consecutive patients with thyroid nodular disease. Basal
      plasma hCT was above the normal range (>6 pg/mL) in 55 patients and was elevated
      up to more than 100 pg/mL (range, 127-5459) in 3 of these 55 patients. A
      pentagastrin-induced rise in hCT up to more than 100 pg/mL was observed in only 1
      of 38 patients with a basal concentration of hCT between 5-10 pg/mL, but was
      found in 10 of 31 patients with basal hCT ranging from 10-100 pg/mL.
      Histologically, 7 of the 14 patients with either basal or stimulated plasma
      concentrations of hCT above 100 pg/mL presented C cell hyperplasia, which in one
      case showed histological transition into a small (diameter, 3 mm) medullary
      thyroid carcinoma (MTC). Including this patient, MTC was found in 6 of the 12
      patients. We conclude that the routine determination of hCT in all patients with
      thyroid nodular disease should be supplemented by pentagastrin-stimulation when
      the basal hCT concentration exceeds 10 pg/mL. Patients with basal and/or
      stimulated plasma CT concentrations of more than 100 pg/mL should be operated on
      because they run a substantial risk to suffer either MTC or C cell hyperplasia, a
      potentially precancerous condition. This will increase the chance of a timely
      diagnosis of MTC and provide the chance of curative surgery.

PMID- 9141555
TI  - Expression of corticotropin-releasing hormone and its R1 receptor in human
      endometrial stromal cells.
AB  - Corticotropin-releasing hormone (CRH) is a hypothalamic neuropeptide that has
      been identified also in several peripheral tissues, including organs of the
      reproductive system. In man, CRH is synthesized and released by the gonads, the
      placenta, maternal decidua, and the epithelial endometrium. So far, CRH has been
      demonstrated in endometrial stromal cells only after decidualization. The aim of
      this study was to seek evidence of the production and secretion of CRH by
      endometrial stromal cells in different phases of the menstrual cycle and to look
      for gene expression of the recently identified CRH receptor R1. Total RNA was
      extracted from stromal cells monolayers established from endometrial samples
      collected during both proliferative and secretive phases. After reverse
      transcription, polymerase chain reaction (PCR) amplification was carried out
      using primers specific to CRH and to CRH receptor R1, resulting in the expected
      bands, respectively 233 bp for CRH and 274 bp for CRH-R1. The identity of the
      obtained CRH PCR product was confirmed by restriction enzyme analysis and by
      Southern blotting. Purification by high performance liquid chromatography (HPLC)
      of stromal cell culture medium revealed a major peak of CRH immunoreactivity
      coeluting with the standard CRH(1-41), thus indicating the secretion of the
      mature peptide. Our study demonstrates the synthesis and secretion of CRH by
      endometrial stromal cells at all phases of the menstrual cycle. We also
      demonstrate the expression of the CRH receptor R1 gene. It can be hypothesized
      that CRH contributes via autocrine/paracrine mechanisms to endometrial
      physiology.

PMID- 9141556
TI  - Metabolism of dexamethasone in the human kidney: nicotinamide adenine
      dinucleotide-dependent 11beta-reduction.
AB  - Recently, two distinct isoenzymes of 11beta-hydroxysteroid-dehydrogenase (11beta
      HSD) have been cloned and characterized in several species: The isoenzyme 11beta
      HSD-I is widely distributed, bidirectional, prefers NADP(H) and has a low
      substrate affinity. The isoenzyme 11beta-HSD-II seems to exclusively oxidize
      physiological glucocorticoids, uses NAD as cosubstrate, has high substrate
      affinity, and is only found in mineralocorticoid target tissues and the placenta.
      Synthetic steroids fluorinated in position 9, however, are rapidly reduced by
      human kidney cortex slices. We attempted to find out which isoenzyme is
      responsible for this unexpected reductase activity. We studied the 11beta-HSD
      activity towards cortisol (F)/cortisone (E) and dexamethasone (D)/11-dehydro
      dexamethasone (DH-D) in microsomes prepared from human kidney cortex. For the
      reaction E to F (not for DH-D to D!), glucose-6-phosphate and glucose-6-phosphate
      dehydrogenase had to be added as a NADH/NADPH-regenerating system. Oxidation of F
      to E: NAD was the exclusively used cosubstrate; the affinity [Michael's constant
      (Km) for F = 25.5 nmol/L] and the maximum velocity (Vmax = 22.9 nmol/mg/min) were
      high. Reduction of E to F: Without the NADH/NADPH-regenerating system, this
      reaction was very slow. With this system, the Km value for E was in the nanomolar
      range (80.6 nmol/L) and the Vmax value was very low (0.88 nmol/mg/min). The
      reaction was clearly NADH-preferring. For the steroid pair F/E, the quotient
      Vmax(oxidation)/Vmax(reduction) (=26) demonstrates an equilibrium far on the 11
      keto side. Oxidation of D to DH-D: With NAD as the only used cosubstrate, the
      kinetic analysis is compatible with the existence of two different NAD-dependent
      isoenzymes: Km for D = 327 nmol/L, Vmax = 53.5 nmol/mg/min and Km for D = 81.2
      nmol/L; Vmax = 20.4 nmol/mg/min. Reduction of DH-D to D: The maximum velocity was
      higher than that of all other reactions tested: Vmax = 226.0 nmol/mg/min. The
      reaction was exclusively NADH-dependent; the Km value for DH-D was 68.4 nmol/L.
      For D/DH-D, the ratio Vmax(oxidation)/Vmax(reduction) was 0.24, demonstrating a
      shift to reductase activity with the reaction equilibrium far on the 11-hydroxy
      side. The reaction F to E was inhibited by E, DH-D, and D in a concentration
      dependent manner. In conclusion, the cosubstrate dependence, the Km value of the
      oxidation of F and the product inhibition are in good correspondence with data
      for the cloned human 11beta-HSD-II. The NADH-dependent 11beta-reduction of E and
      especially of DH-D are inconsistent with the dogma of an unidirectional 11beta
      HSD-II. The preference of D for the reductase reaction in human kidney slices is
      probably caused by the fluor atom in position 9, is catalyzed by 11beta-HSD-II,
      and leads to an activation of 11-DH-D to D in the human kidney.

PMID- 9141557
TI  - Differential effect of gender on the sizes of the bones in the axial and
      appendicular skeletons.
AB  - Recent observations suggest that throughout life the size of the vertebral bodies
      in females is smaller than that in males even after accounting for differences in
      body size. To confirm these reports and to determine whether similar differences
      exist in the appendicular skeleton, detailed measurements of the sizes of the
      vertebrae and the femur were obtained using computed tomography in 30 pairs of
      prepubertal boys and girls matched for age, height, and weight. Anthropometric
      parameters as well as gender influenced the cross-sectional area of the
      vertebrae. Heavier children had greater vertebral cross-sectional area than
      slender children regardless of gender, and the vertebral bodies were found to be
      significantly smaller in girls than in matched boys (approximately 11%), both
      using Student's t test (P < 0.0001) and its multivariate analog, the Hotelling's
      T2 test (P < 0.0001). In contrast to these findings in the axial skeleton, gender
      status did not influence the size of the bones in the appendicular skeleton, and
      neither the cross-sectional area (3.28 +/- 0.84 vs. 3.10 +/- 0.56 cm2) nor the
      cortical bone area (1.80 +/- 0.37 vs. 1.85 +/- 0.36 cm2) at the midshaft of the
      femur differed between boys and girls. These values, however, correlated strongly
      with all anthropometric indexes, and multiple regression analyses indicated that
      both measurements were primarily related to weight. The results suggest that
      although increases in mechanical loading associated with growth are the main
      determinant of the cross-sectional properties of the appendicular skeleton in
      children, factors other than body mass and related to gender have a significant
      role in the regulation of the sizes of the bones in the axial skeleton.

PMID- 9141559
TI  - In situ evidence of neoplastic cell phagocytosis by macrophages in papillary
      thyroid cancer.
AB  - We evaluated the occurrence, tissue distribution, and prognostic value of tumor
      associated macrophages in 121 papillary thyroid carcinomas using
      immunohistochemical staining with anti-CD68 antibody in archival paraffin
      embedded sections. Lymphocytic infiltration and dendritic cell presence were also
      evaluated. Three groups were identified according to the presence and
      characteristics of macrophages: 1) tumors without evidence of infiltrating
      macrophages: (n = 35); 2) tumors with infiltrating macrophages but no evidence of
      neoplastic cells phagocytosis (n = 68); and 3) tumors with infiltrating
      macrophages and in situ evidence of active neoplastic cell phagocytosis (n = 18).
      Neoplastic cell phagocytosis by macrophages was positively correlated with both
      lymphocytic infiltration and dendritic cells (P = 0.0000), whereas it was
      negatively correlated with vascular invasion (P = 0.0032). Distant metastases
      developed in none of the 18 tumors with neoplastic cell phagocytosis, but
      occurred in 15 of 103 of the remaining tumors (P = 0.0647) and were significantly
      and negatively associated with lymphocytic infiltration or dendritic cells. The
      present study indicates, therefore, that immune reaction, involving neoplastic
      cell phagocytosis by macrophages and lymphocytic infiltration, plays a role in
      the development of distant metastases in patients with papillary thyroid cancer.

PMID- 9141558
TI  - Resistance to thyroid hormone caused by two mutant thyroid hormone receptors
      beta, R243Q and R243W, with marked impairment of function that cannot be
      explained by altered in vitro 3,5,3'-triiodothyroinine binding affinity.
AB  - Resistance to thyroid hormone (RTH) is a syndrome of reduced responsiveness to
      thyroid hormone caused by mutations in the thyroid hormone receptor beta (TRbeta)
      gene. Mutant TRbetas exhibit variable degrees of impaired T3 binding resulting in
      reduced T3-mediated function. The dominant mode of inheritance is attributed to
      the ability of mutant TRbetas to interfere with the function of the wild-type
      (WT) TR, a phenomenon known as dominant negative effect (DNE). We recently
      identified two families with RTH having mutations in amino acid 243 (R243Q and
      R243W) in whom the mechanism of RTH appears to be distinct from that of other
      natural TRbeta mutations. These mutations, which are located in the hinge domain
      of the TRbeta, do not significantly alter the binding affinity for T3, measured
      in vitro. The present study was undertaken to characterize the properties of
      these mutant TRbetas to understand the molecular basis of the RTH phenotype. Two
      other mutant TRbeta producing RTH with mild (320H) and severe (345R) impairment
      of T3 binding were studied in parallel. The results demonstrate that TRbetas 243Q
      and 243W could be translocated into the nucleus where they exerted normal ligand
      independent repression of positively regulated thyroid hormone response elements.
      Yet, the addition of 10 nmol/L T3 failed to normalize the transactivation (16-13%
      of WT) and revert the DNE exerted by the two TRbeta mutants. In contrast, at this
      T3 concentration, the transactivation function of 320H was significantly higher
      (50% of WT), and the DNE was completely abolished, in keeping with the mild
      clinical form of RTH. Formation of 243Q and 243W homodimers on thyroid hormone
      response elements could not be as readily prevented by T3 as those formed by the
      WT and 320H TRbetas. These results suggest that the substitution of R243 in
      TRbeta produces RTH by increasing the propensity for the formation of tightly
      bound homodimers or by reduction of the receptor affinity for T3 only after it
      binds to DNA.

PMID- 9141560
TI  - Immunolocalization and regulation of the chemokine RANTES in human endometrial
      and endometriosis tissues and cells.
AB  - Retrograde menstruation is postulated as the initiating event in the histogenesis
      of endometriosis; however, subsequent steps in the pathogenesis of this common
      disorder remain poorly characterized. The ip accumulation of activated leukocytes
      and the infiltration of endometriosis lesions by macrophages and T cells are
      cytological markers of the inflammatory nature of this syndrome. The apparent
      recruitment of these leukocytes prompted us to search for chemokine expression by
      endometriosis cells. We reported previously that pelvic fluid RANTES (regulated
      upon activation, normal T cell expressed and secreted) concentrations correlated
      with the stage of endometriosis. In the current study, RANTES messenger
      ribonucleic acid (mRNA) was identified in normal endometrium and endometriosis
      lesions, and techniques were developed to localize RANTES protein within these
      tissues. Using isolated endometrial and endometriosis cell cultures, we
      demonstrated that RANTES mRNA and protein can be induced by the proinflammatory
      cytokines tumor necrosis factor-alpha and interferon-gamma in endometrial
      stromal, but not in epithelial or adenocarcinoma cells. Immunocytochemical
      studies confirmed the biochemical findings. Metabolic labeling experiments
      verified that nascent RANTES secreted by cytokine-stimulated endometriosis
      stromal cells was the mature, 8-kDa protein predicted by the mRNA encoding this
      chemokine. The results indicate that RANTES is a normal constituent of the
      eutopic endometrium. We propose that secretion of RANTES by ectopic endometriosis
      implants provides a mechanism for peritoneal leukocyte recruitment.

PMID- 9141561
TI  - A novel point mutation in the insulin gene giving rise to hyperproinsulinemia.
AB  - A 58-yr-old obese white Caucasian male type 2 diabetic, entered into the UK
      Prospective Diabetes Study, was found to have raised fasting total proinsulin
      levels 708 pmol/L(-1) (normal range, 3-16 pmol/L(-1)) and normal specific plasma
      insulin level 29 pmol/L(-1) (normal range, 21-75 pmol/L(-1)). Immunoreactive
      plasma insulin, measured by RIA, was 503 pmol/L(-1). DNA was extracted, the
      insulin gene amplified by the PCR, and by direct sequencing, a novel point
      mutation, G1552C, was identified, which resulted in the substitution of proline
      (CCT) for arginine (CGT) at position 65. This prevented cleavage of the C-peptide
      A-chain dibasic cleavage site (lys-arg) by the processing protease in the
      pancreatic beta-cells. The plasma proinsulin and insulin levels were in accord
      with expression of both the wild-type and the mutant alleles. The G1552C mutation
      was not linked with diabetes, because it was present in a 37-yr-old nondiabetic
      daughter and not in a 35-yr-old daughter who had had gestational diabetes.

PMID- 9141562
TI  - Influence of thyroid status on serum immunoreactive leptin levels.
AB  - Leptin, the product of the ob gene, is a recently discovered hormone secreted by
      adipocytes. Serum leptin concentrations increase in correlation with the
      percentage of body fat, but besides that, little is known about the physiological
      actions of leptin in humans. The aim of this study was to assess the influence of
      hypo- and hyperthyroidism on serum leptin levels. Thirty-two patients (16 with
      hypothyroidism and 16 with hyperthyroidism) were studied before and after
      treatment with replacement doses of T4 (hypothyroid patients) or methimazole
      (hyperthyroid), when thyroid function was normal. Control serum for each group
      was obtained from healthy age-, sex-, and body mass index-matched subjects.
      Plasma leptin levels were measured by specific RIA. The mean leptin level in the
      hypothyroid patients was lower before treatment (4.7 +/- 0.7 microg/L) than that
      in the controls (8.6 +/- 1.4 microg/L; P < 0.02) and was lower than that during
      treatment with T4 and normalization of thyroid function in the same group of
      patients (6.3 +/- 0.8 microg/L; P < 0.05). Leptin levels in the hyperthyroid
      patients were similar before (7.2 +.0 1.1 microg/L) and after normalization of
      thyroid function following treatment with methimazole (6.2 +/- 1.1 microg/L) and
      were similar to the control value (8.8 +/- 1.4 microg/L). In conclusion, leptin
      levels are decreased in the hypothyroid patients and unchanged in
      hyperthyroidism. Whether decreased leptin levels may contribute to the decreased
      energy expenditure in patients with hypothyroidism merits further investigation.

PMID- 9141563
TI  - Dexamethasone increases leptin expression in humans in vivo.
AB  - The effect of 2 days of oral dexamethasone administration (0.75 mg twice daily)
      on leptin expression in healthy volunteers was tested. Dexamethasone increased
      the relative abundance of leptin messenger RNA in abdominal and gluteal adipose
      tissues by approximately 70% (P < 0.05). Dexamethasone also significantly
      increased serum leptin (+ 80%) and insulin concentration (+ 83%) but did not
      affect serum glucose. We conclude that a hypercortisolemic/hyperinsulinemic state
      up-regulates leptin expression at the messenger RNA level in humans.

PMID- 9141564
TI  - Early diagnosis by genetic analysis of differentiated thyroid cancer metastases
      in small lymph nodes.
AB  - We report a PCR-based technique for detecting thyroid cancer metastases in small
      nodes <1.5 cm diameter by the amplification of thyroid specific transcripts TSH
      receptor and thyroglobulin. A 100% correspondence with the histopathological
      diagnosis was observed in the 41/46 nodes (89%) in which an adequate sample was
      obtained at fine needle aspiration. The genetic analysis resulted more sensitive
      and accurate than both the cytological analysis (28% inadequate samples, 17%
      false negative diagnoses) and the thyroglobulin measurement in the aspirates (39%
      false negatives). The PCR-based genetic analysis may provide a useful tool for
      diagnosis and follow-up of thyroid cancer.

PMID- 9141565
TI  - Serum leptin concentration in cord blood: relationship to birth weight and
      gender.
AB  - To investigate the effect of leptin on fetal growth, serum leptin concentrations
      in venous cord blood were measured in 82 newborns (male = 43, female = 39,
      gestational age 36-42 weeks, birth weight 2,306-4,128 g). Serum leptin
      concentrations in cord blood ranged from 2.0 to 84.5 ng/mL (mean 19.9 +/- 17.4
      ng/mL). Serum leptin concentrations in males (mean 15.3 +/- 15.6 ng/mL, range 2.0
      to 79.3 ng/mL) were significantly (P = 0.011) lower than those in females (mean
      25.0 +/- 18.0 ng/mL, range 2.1 to 84.5 ng/mL). Serum leptin concentrations in
      cord blood were positively correlated with birth weight (r = 0.555, P <0.0001),
      birth weight SD (r = 0.540, P <0.0001), Kaup index (r = 0.505, P <0.0001) and
      body weight/body height (r = 0.560, P <0.0001). The serum concentrations of
      estradiol and testosterone did not differ between males and females and did not
      correlate with the leptin concentration. It is unlikely that the gender
      difference in fetal leptin levels is due either to body fat content or
      distribution or to reproductive hormone status, but may be attributed to genetic
      differences between males and females.

PMID- 9141566
TI  - Mapping of a major susceptibility locus for Graves' disease (GD-1) to chromosome
      14q31.
AB  - The autoimmune thyroid diseases (AITD), encompassing Graves' disease (GD) and
      Hashimoto's thyroiditis (HT), occur in genetically susceptible individuals. In
      order to identify the AITD susceptibility genes, we have studied DNA markers in
      the regions of 8 candidate genes: (1) the HLA region, (2) the TSH receptor, (3)
      thyroid peroxidase, (4) thyroglobulin, (5) IDDM-4, (6) IDDM-5, (7) Immunoglobulin
      heavy chain gene and (8) CTLA-4. One hundred and seven subjects from 19
      informative families were studied, 14 subjects had GD and 32 subjects had HT. LOD
      scores were maximized assuming both dominant and recessive modes of inheritance.
      No linkage was found for any marker in patients with HT. In patients with GD,
      negative LOD scores were obtained for all the candidate genes, except for markers
      in the TSH receptor region on chromosome 14q31. Positive LOD scores were found
      for several markers on 14q31. Marker D14S81 gave the highest score (Z max = 2.05,
      theta = 0.01) assuming a dominant mode of inheritance and a penetrance of 0.8.
      These data confirm our previous observations of a lack of a necessary disease
      locus for AITD in the HLA gene region. Further, the data suggest the presence of
      an important susceptibility gene on 14q31 but at a considerable distance from the
      TSH receptor gene.

PMID- 9141567
TI  - Commentary on article by Hobbs, Jones, and Plymate.

PMID- 9141568
TI  - Massive hypertriglyceridemia complicating estrogen therapy.

PMID- 9141569
TI  - Prevalence, significance, and biological behavior of ret/PTC1 associated
      papillary thyroid carcinoma.

PMID- 9141570
TI  - Evidence-based audit?

PMID- 9141571
TI  - The whole duty of obstetricians.

PMID- 9141572
TI  - Umbilical artery Doppler--more harm than good?

PMID- 9141573
TI  - Midwife-led care.

PMID- 9141574
TI  - Abortion after 24 weeks.

PMID- 9141575
TI  - Adhesion molecules in reproduction.

PMID- 9141576
TI  - The Stockholm birth centre trial: maternal and infant outcome.
AB  - OBJECTIVE: To compare an in-hospital birth centre with standard maternity care
      regarding medical interventions and maternal and infant outcome. BACKGROUND: The
      birth centre care was characterised by comprehensive antenatal, intrapartum and
      postpartum care with the same team of midwives, restricted use of medical
      technology, and discharge within 24 h after birth. METHODS: Of 1860 women meeting
      low risk medical criteria in early pregnancy and interested in birth centre care,
      928 were randomly allotted birth centre care and 932 standard maternity care.
      Data were collected mainly from hospital records, and analysis was by intention
      to-treat. RESULTS: Of the women in the birth centre group, 13% were transferred
      antenatally and 19% intrapartum. No statistical differences were observed in
      maternal morbidity or in perinatal mortality, neonatal morbidity, Apgar score or
      infant admissions to neonatal care. Perinatal mortality, defined as intrauterine
      death after 22 weeks of gestation and infant death within seven days of birth,
      occurred in eight cases (0.9%) in the birth centre group and in two cases (0.2%)
      in the standard care group (OR 4.04, 95% CI 0.80 to 39.17; P = 0.11). Subgroup
      analysis showed that a larger proportion of first-born babies in the birth centre
      group (15.6%) were admitted for neonatal care than in the standard care group
      (9.5%) (P = 0.003), whereas the converse was the case for the newborns of
      multiparous women: 4.7% and 8.4%, respectively (P = 0.04). The overall rates of
      operative delivery (e.g. caesarean section, vacuum extraction and forceps), 11.1%
      in the birth centre group and 13.4% in the standard care group, did not differ
      statistically (P = 0.12), but obstetric analgesia, induction, augmentation of
      labour and electronic fetal monitoring were less frequently used in the birth
      centre group. Labour was 1 h longer in the birth centre group. CONCLUSION: Birth
      centre care was associated with less medical interventions than standard care
      without any statistically significant differences in health outcomes. However,
      the excess of perinatal deaths and of morbidity in primigravidas' infants in the
      birth centre group gives cause for concern and necessitates further studies.

PMID- 9141577
TI  - A randomised controlled trial of Doppler ultrasound velocimetry of the umbilical
      artery in low risk pregnancies. Doppler French Study Group.
AB  - OBJECTIVE: To evaluate the effect on management and outcome of pregnancy of
      routine umbilical Doppler examination in low risk populations. DESIGN: Pragmatic
      randomised controlled trial. SETTING: Twenty centres caring for low risk pregnant
      women. PARTICIPANTS: 4187 women were randomly assigned to umbilical Doppler
      between 28 and 34 weeks of gestation or no routine umbilical Doppler. The women
      included were at low risk at 28 weeks of gestation defined by a normal
      ultrasonographic examination at the time of randomisation and no obstetric or
      medical complications during the first two trimesters of the pregnancy. RESULTS:
      The general characteristics at inclusion were comparable for the two groups.
      Performance of umbilical Doppler led to a significant increase in the number of
      ultrasonographic and Doppler examinations subsequently conducted; there were no
      other effects on the management of the pregnancy. There was no significant
      difference in fetal distress during labour (odds ratio [OR] 0.96; 95% confidence
      interval [CI] 0.70-1.33). There were three times fewer perinatal deaths in the
      Doppler group (three versus nine), but this difference was not significant (OR
      0.33; 95% CI 0.06-1.33). CONCLUSION: Based on this trial routine use of umbilical
      doppler for low risk pregnancy cannot be recommended. More data are needed to
      reach a definite conclusion of the value of routine Doppler.

PMID- 9141578
TI  - Umbilical artery Doppler velocimetry in unselected and low risk pregnancies: a
      review of randomised controlled trials.
AB  - OBJECTIVE: Meta-analysis of data from controlled trials performed in populations
      at high risk have shown that umbilical artery Doppler velocimetry (umbilical
      Doppler) can reduce perinatal mortality. The individual published trials among
      unselected or low risk populations have found no beneficial effect. Our objective
      was to evaluate the effect of routine use of the umbilical Doppler in unselected
      or low risk pregnancies by reviewing all published and unpublished randomised
      controlled trials. STUDY DESIGN: Systematically reviewing published and
      unpublished trials, we selected trials for the overview only if they were
      completed randomised trials of umbilical Doppler in unselected or low risk
      pregnancies. Of the seven trials examined, three were not included in the meta
      analysis because of methodological problems or because they did not meet the
      inclusion criteria. We therefore included four trials: two in unselected and two
      in low risk populations. These four groups were comparable in their degree of
      maternal and perinatal risk. Using the Mantel-Haenzel statistical method and
      pooling the data, we considered 11,375 women in the meta-analysis. RESULTS:
      Systematic use of the Doppler umbilical artery velocimetry had no statistically
      significant effect on perinatal deaths in unselected populations (odds ratio [OR]
      1.28; 95% confidence interval [CI] 0.61-2.67), low risk populations (OR 0.51; 95%
      CI 0.20-1.29) or overall for the four trials (OR 0.90; 95% CI 0.50-1.60); nor was
      there any significant effect on stillbirths (global OR 0.94; 95% CI 0.42-1.98).
      However, the number of participants remain insufficient and further information
      is required to arrive at a definite conclusion on the absence of effect. The meta
      analysis showed no significant difference between the Doppler groups and the
      control groups for antenatal hospitalisation, obstetric outcome or perinatal
      morbidity. CONCLUSION: Based on the results of the published trials, routine use
      of the umbilical Doppler cannot be recommended.

PMID- 9141579
TI  - Randomised controlled trial of cardiotocography versus umbilical artery Doppler
      in the management of small for gestational age fetuses.
AB  - OBJECTIVE: To compare the impact on use of resources in the management of small
      for gestational age babies using Doppler ultrasound versus cardiotocography.
      DESIGN: A randomised controlled trial. SETTING: A large district general hospital
      delivering 5500 to 6000 infants each year, 30% to 35% of which are to women of
      Pakistani origin. POPULATION: One hundred and fifty women delivered of small for
      gestational age infants. MAIN OUTCOME MEASURES: Primary outcome measures were
      length of hospital inpatient stay and induction of labour rates. Secondary
      outcome measures included caesarean section rates and length of stay on neonatal
      unit. RESULTS: The use of Doppler reduced average hospital inpatient stay from
      2.5 days to 1.1 days, compared with cardiotocography (P = 0.036). There was no
      effect on induction of labour rates or caesarean section rates. There was no
      significant difference in length of stay on the neonatal unit (P = 0.33). There
      was a reduction in monitoring frequency and fewer hospital antenatal clinic
      visits. CONCLUSION: The use of Doppler ultrasound to manage small for gestational
      age infants reduces the use of resources, compared with cardiotocography.

PMID- 9141580
TI  - The diagnostic accuracy of cervico-vaginal fetal fibronectin in predicting
      preterm delivery: an overview.
AB  - OBJECTIVE: To determine the accuracy with which cervico-vaginal fetal fibronectin
      predicts preterm delivery using systematic quantitative overview of the available
      literature. DESIGN: Online searching of MEDLINE database (1966 to April 1996),
      scanning of bibliography of known primary and review articles and review of
      recent journal issues. Study selection, assessment of study quality and data
      extraction were performed in duplicate under masked conditions. Likelihood ratios
      were generated in subgroups of symptomatic and asymptomatic pregnant women by
      pooling data from different studies. An LR of > 10 or < 0.1 indicated conclusive
      changes in the pretest probability of preterm delivery while an LR of 5-10 or 0.2
      0.1 indicated only moderate changes. PARTICIPANTS: Seven hundred and twenty-three
      symptomatic women with threatened preterm labour included in nine studies and 847
      asymptomatic women (635 low risk and 212 high risk) included in six studies
      selected for meta-analyses. MAIN OUTCOME MEASURES: Likelihood ratios for positive
      and negative test results using delivery at < 37 and < 34 weeks of gestation, and
      within one week of testing as outcome measures. RESULTS: In symptomatic women a
      positive test predicted delivery < 37 weeks of gestation with a pooled likelihood
      ratio (LR) of 4.6 (95% CI 3.5-6.1) while a negative test had a pooled LR of 0.5
      (95% CI 0.4-0.6). For delivery < 34 weeks of gestation, the pooled LR was 2.6
      (95% CI 1.8-3.7) for a positive test and 0.2 (95% CI 0.1-0.5) for a negative
      test. For delivery within one week of testing, the pooled LR was 5.0 (95% CI 3.8
      6.4) for a positive test and 0.2 (95% CI 0.1-0.4) for a negative test. In
      asymptomatic women at low risk of delivery < 37 weeks of gestation the pooled LR
      was 3.2 (95% CI 2.2-4.8) for a positive test and 0.8 (95% CI 0.7-0.9) for a
      negative test. In high risk asymptomatic women using delivery < 37 weeks of
      gestation as an outcome measure the pooled LR was 2.0 (95% CI 1.5-2.6) for a
      positive test and 0.4 (95% CI 0.2-0.8) for a negative test. For delivery < 34
      weeks of gestation in high risk, asymptomatic women the pooled LR was 2.4 (95% CI
      1.8-3.2) for a positive test and 0.6 (95% CI 0.4-0.9) for a negative test.
      CONCLUSION: The presence of fetal fibronectin in cervico-vaginal mucus has
      limited accuracy in predicting preterm delivery as the likelihood ratios for
      positive and negative test results generated only minimal to moderate changes in
      the pretest probability of preterm birth.

PMID- 9141581
TI  - Fetal size and growth velocity in the prediction of intrapartum caesarean section
      for fetal distress.
AB  - OBJECTIVE: To evaluate and compare third trimester ultrasound measurements of
      fetal size and growth velocity in the prediction of intrapartum operative
      delivery for fetal distress and admission to the special care baby unit in a low
      risk antenatal population undergoing labour at term. DESIGN: Retrospective
      analysis of prospectively collected ultrasound data. SETTING: Ninewells Hospital,
      Dundee, Scotland. POPULATION: Three hundred and ninety-eight women previously
      enrolled in a longitudinal study of intrauterine volume undergoing labour at a
      gestational age of > 37 weeks. METHOD: Fetal abdominal area (FAA) standard
      deviation scores (Z scores) were calculated for size at 32 and 36 weeks of
      gestation together with the growth velocity Z scores between these two
      gestational ages. Receiver-operator characteristics were calculated for fetal
      abdominal area Z scores at 32, 36 weeks and velocity Z scores in the prediction
      of caesarean section for fetal distress and/or admission to the special care baby
      unit. MAIN OUTCOME MEASURES: Intrapartum caesarean section for fetal distress and
      admission to the special care baby unit with a diagnosis of perinatal hypoxia.
      RESULTS: Pregnancies ending in caesarean section for fetal distress or admission
      to the special care baby unit (n = 17) had significantly lower fetal abdominal
      area Z scores at 36 weeks of gestation (mean Z score -0.71 vs -0.18) and lower
      fetal abdominal area growth velocity (mean Z score - 1.31 vs -0.01). Taking a
      cutoff Z score of -1.2 derived from the receiver-operator characteristic curve,
      fetal abdominal area velocity has a sensitivity of 65% and specificity 75% for
      caesarean section for fetal distress and/or admission to the special care baby
      unit. CONCLUSION: Growth velocity of the fetal abdominal area in the third
      trimester is superior to a single measurement of the fetal abdominal area at
      either a mean of 32 or 36 weeks of gestation in the prediction of caesarean
      section for fetal distress and admission to the special care baby unit in low
      risk women labouring at term. These results support the hypothesis that in the
      third trimester at least, growth rate in utero is more relevant to intrapartum
      performance and immediate perinatal outcome than estimates of fetal size alone.

PMID- 9141582
TI  - A meta-analysis of low dose aspirin for the prevention of intrauterine growth
      retardation.
AB  - OBJECTIVE: To determine more precisely the effect of prophylactic low dose
      aspirin on intrauterine growth retardation and perinatal mortality. DESIGN: Meta
      analysis of 13 published randomised clinical trials. METHODS: We searched 18
      medical databases, including MEDLINE since 1964 and EMBASE since 1974, review
      articles and the references from each retrieved report to identify all studies
      evaluating the effect of aspirin in pregnancy and including both intrauterine
      growth retardation and perinatal mortality as outcome measures. RESULTS: Among
      13,234 women from 13 studies between 1985 and 1994, aspirin showed a significant
      reduction in intrauterine growth retardation (IUGR) (OR 0.82; 95% CI 0.72-0.93; P
      = 0.003) and a nonsignificant reduction in perinatal mortality (OR 0.84; 95% CI
      0.66-1.08; P = 0.18). Subgroup analyses revealed that aspirin was effective at
      lower doses between 50 and 80 mg/day (IUGR: OR 0.87; 95% CI 0.76-0.99; mortality:
      OR 0.90, 95% CI 0.70-1.16), but that the preventive effect was greater at higher
      doses between 100 and 150 mg/day (IUGR: OR 0.36, 95% CI 0.22-0.59; mortality: OR
      0.40, 95% CI 0.16-0.97) and among women entered before the 17th week of gestation
      (IUGR: OR 0.35, 95% CI 0.21-0.58; mortality: OR 0.43, 95% CI 0.17-1.06). We did
      not identify any specific subgroup of women most likely to benefit from aspirin
      treatment. CONCLUSION: The results of this meta-analysis showed that early
      aspirin treatment reduced the risk of intrauterine growth retardation. Low dose
      aspirin should not be used routinely in pregnant women until those most likely to
      benefit from aspirin treatment have been clearly identified.

PMID- 9141583
TI  - The effect of carotid sinus denervation on fetal heart rate variation in
      normoxia, hypoxia and post-hypoxia in fetal sheep.
AB  - OBJECTIVE: To investigate whether carotid sinus nerve reflexes are linked to the
      increase in heart rate variation in acute (one hour) hypoxia in late gestation
      fetal sheep DESIGN: Comparison of short term variation between intact and carotid
      sinus denervated fetuses in normoxia, hypoxia and post-hypoxia. SUBJECTS: Sixteen
      chronically catheterised pregnant sheep in late gestation. RESULTS: There was no
      significant difference in short term variation between intact and denervated
      fetuses in normoxia. In intact fetuses short term variation increased
      significantly in hypoxia. In denervated fetuses it tended to increase in hypoxia,
      but this was not statistically significant. During the post-hypoxia period, short
      term variation increased significantly in denervated fetuses, although at this
      time it was decreasing in intact fetuses. When the decrease in pH was small
      intact fetuses showed a significantly greater increase in short term variation
      than denervated fetuses in hypoxia. In contrast, short term variation increased
      similarly in both groups when the pH decrease was greater (> 0.03 in early
      hypoxia and > 0.05 in late hypoxia). CONCLUSIONS: Carotid sinus nerve reflexes
      have an important influence on heart rate variation in hypoxia and post-hypoxia.
      It appears that other mechanisms (e.g. a rise in circulating catecholamines) are
      linked to an increase in heart rate variation when mild acidemia occurs in
      hypoxia.

PMID- 9141584
TI  - Increased levels of intercellular adhesion molecules and vascular cell adhesion
      molecules in pre-eclampsia.
AB  - OBJECTIVE: To investigate the correlation between soluble forms of the
      intercellular adhesion molecule (sICAM-1) and vascular cell adhesion molecule
      (sVCAM-1) and the severity of pre-eclampsia or its possible consequences for
      fetal growth. DESIGN: Prospective observational study. SETTING: Institute of
      Medical Genetics, University of Oslo, Department of Medical Genetics and
      Haematological Research Laboratory, Ulleval University Hospital; and the
      Department of Obstetrics and Gynaecology, The National Hospital, Oslo, Norway.
      PARTICIPANTS: Seventy-six women with normotensive pregnancies and 157 women with
      pre-eclampsia divided into three subgroups: mild, severe and pre-eclampsia with
      fetal growth retardation. METHODS: ELISA-measurements of plasma sICAM-1 and sVCAM
      1 were performed in a group of healthy pregnant normotensive women and three
      groups of women with varying degrees of pre-eclampsia. RESULTS: sICAM-1
      concentrations were higher in the pre-eclampsia group compared with the control
      group, but this difference was not statistically significant. Plasma
      concentrations of sVCAM-1 were significantly greater (P < 0.0001) in all pre
      eclampsia subgroups (835.34, 855.25 and 964.05 ng/mL) compared with the control
      group (667.62 ng/mL). Within the pre-eclampsia group, plasma concentration of
      sVCAM-1 was significantly higher in the subgroup exhibiting fetal growth
      retardation (P = 0.03) compared with mild pre-eclampsia. CONCLUSION: The observed
      increases in plasma concentrations of sVCAM-1 suggest that measurements of this
      adhesion molecule may be useful in monitoring pregnancies with respect to the
      development of pre-eclampsia or fetal growth retardation.

PMID- 9141585
TI  - Effects of SR 49059, an orally active V1a vasopressin receptor antagonist, on
      vasopressin-induced uterine contractions.
AB  - OBJECTIVE: To test the effect of SR 49059, an orally active, nonpeptide,
      selective and specific antagonist of the vasopressin V1a receptors in humans.
      DESIGN: A placebo-controlled, double-blind, cross-over trial. SETTING: The
      Department of Obstetrics and Gynaecology, Lund University Hospital, Sweden.
      PARTICIPANTS: Twelve healthy women, who had previously been sterilised by tubal
      ligation. INTERVENTIONS: The women participated on days 1, 2 or 3 of two
      menstrual cycles, with intrauterine pressure recordings and intravenous bolus
      injections of 10 pmol/kg body weight of lysine vasopressin given 1 h before and
      at 1, 2 and 3 h after oral administration of 300 mg of the study drug or of
      placebo. MAIN OUTCOME MEASURE: The area between the recording curve and zero
      level of pressure. Vital signs, safety parameters and drug plasma concentrations
      were also measured. RESULTS: The spontaneous uterine activity as well as the
      response to lysine vasopressin injections before administration of the test drugs
      were almost identical at the two experiments. Following intake of SR 49059 the
      area under the recording curve (0-10 min) after the second, third, and fourth
      injection of lysine vasopressin were reduced by 57, 42, and 66%, respectively,
      compared with placebo. Trough plasma concentrations of lysine vasopressin were
      markedly higher and systolic blood pressure slightly lower after antagonist
      administration than after placebo, whereas no significant difference between
      treatments was observed in diastolic pressure, heart rate or plasma osmolality.
      CONCLUSIONS: This study demonstrates for the first time a biological effect of an
      orally active vasopressin V1a antagonist in humans in vivo and the results
      support the importance of vasopressin in uterine activation. The differences
      between study drug and placebo treatments in lysine vasopressin levels and
      systolic blood pressure, but lack of difference in osmolality indicate that SR
      49059 antagonises the effect of lysine vasopressin on the vasopressin V1a
      receptor, but not that on the vasopressin V2 one. It is suggested that SR 49059
      be explored therapeutically in dysmenorrhoea.

PMID- 9141586
TI  - Late termination of pregnancy in North Holland.
AB  - OBJECTIVES: To estimate the extent to which late termination of pregnancy
      (gestational period > 24 weeks) is practised, to find out what fetal diseases and
      abnormalities lead to termination and to obtain insight into the clinical
      judgement and decision-making process by gynaecologists with regard to
      termination. DESIGN: A retrospective study. PLACE: Province of North Holland, The
      Netherlands. METHODS: An anonymous printed questionnaire, was sent to all
      associations or departments of gynaecology in the 21 hospitals in North Holland.
      The period of study covered the years 1990 to 1994. RESULTS: Completed
      questionnaires were received from 19 associations or departments in the 21
      hospitals (90% response). In the five-year period under study in 14 of these
      hospitals had terminated 103 pregnancies beyond the 24th week of gestation.
      Antenatal sonography had been performed on all these pregnancies. Anencephaly was
      diagnosed before termination in 21% and severe chromosomal defects in a further
      21%. Other severe abnormalities were neural groove defects, such as hydrocephaly
      and/or spina bifida (16%), no renal function (12%) and skeletal abnormalities
      (11%). In 87% the antenatal diagnosis was verified postnatally; in 78% this was
      done by autopsy. The diagnosis was confirmed in all these cases ('almost
      confirmed' in two cases). In every case the pregnant woman herself had asked for
      her pregnancy to be terminated. In 78% the prognosis was discussed with other
      medical specialists and the professionals concerned with management; there was a
      consultation about the termination in 91% of the cases. A report was always
      compiled for the medical records. CONCLUSION: Late termination of pregnancy is
      practised on a substantial scale in North Holland. The reasons for termination
      were severe structural abnormalities which, in most cases, were not compatible
      with survival. The gynaecologists in North Holland dealt prudently and
      responsibly with late termination of pregnancy, although they did not always
      adhere to the guidelines set out in the 1994 report of the Netherlands
      Association for Obstetrics and Gynaecology.

PMID- 9141587
TI  - Experience of Finnish women with Norplant insertions and removals.
AB  - OBJECTIVE: Norplant and Norplant-2 have been available for use by Finnish women
      since 1984 and 1986, respectively. The objective of this study was to explore
      Norplant users' experiences of insertions, removals and medical treatments.
      DESIGN: A questionnaire was sent to women who had received Norplant or Norplant-2
      implants one to two years earlier (n = 262) in normal clinical settings; the
      response rate was 79%. RESULTS: At insertion, problems were experienced by 9% and
      at least some pain by 23% of women. During the first year 20% of all users (14%
      of Norplant and 33% of Norplant-2 users) had their implants removed. Problems
      were experienced at removal by 33% of women and pain was experienced by 40%;
      nevertheless most users were satisfied with the device. Findings were similar for
      the two types of Norplant. Forty-two percent of the women had received minipills
      containing levonorgestrel before Norplant insertions in an attempt to assess
      Norplant's suitability, and 8% had received drugs for adverse effects caused by
      Norplant. CONCLUSIONS: Studies including perspectives of Norplant users and the
      whole lifespan of Norplant (including removal) should be conducted in all
      clinical settings where Norplant is provided.

PMID- 9141588
TI  - Bradykinin stimulates interleukin-6 and interleukin-8 secretion of human decidua
      derived cells.
AB  - Cytokines are known to participate in the process of parturition within a
      paracrine network in fetal membranes. Bradykinin can also contribute to this
      process, increasing the release of eicosanoids from decidua cells. In this study,
      we present evidence for a cross-link between bradykinin and the cytokines. Short
      and long term cultures of human decidua cells were incubated for 4 h and 24 h
      with and without bradykinin. IL-6 and IL-8 were determined in the supernatants by
      ELISA. Results show a large interindividual variability in the basal secretion of
      IL-6 and IL-8 and a clear increase in the secretion of both ILs in response to
      bradykinin. By this amplifying effect on cytokine secretion, bradykinin can
      initiate local and systemic effects of amniochorionitis.

PMID- 9141589
TI  - Interleukin-8 in urine: a new diagnostic parameter for intra-amniotic infection
      after premature rupture of the membranes.
AB  - Interleukin-8 (IL-8), a 72 amino acid peptide secreted by cells of the immune
      system and of the amnion, chorion and decidua, was measured in women in late
      pregnancy. IL-8 was detected in the urine of 91 of 104 women with premature
      rupture of the fetal membranes, with values exceeding 1000 ng/L in cases of
      severe intra-amniotic infection. Women with urinary tract infections were
      excluded. The routine measurement of IL-8 in urine, together with C-reactive
      protein in serum, thus provides a low risk and technically simple approach to the
      assessment of intra-amniotic infection.

PMID- 9141590
TI  - Prenatally detected reversal of donor-recipient roles in twin-to-twin transfusion
      syndrome following in utero treatment.

PMID- 9141591
TI  - Perineal delivery in Ehlers-Danlos syndrome.

PMID- 9141592
TI  - Medico-legal aspects of ureteric damage during abdominal hysterectomy.

PMID- 9141593
TI  - Medico-legal aspects of ureteric damage during abdominal hysterectomy.

PMID- 9141594
TI  - Correspondence. Choice and instrumental delivery.

PMID- 9141595
TI  - Persistent ectopic pregnancy following conservative surgery for tubal pregnancy.

PMID- 9141596
TI  - Persistent ectopic pregnancy following conservative surgery for tubal pregnancy.

PMID- 9141597
TI  - Persistent ectopic pregnancy following conservative surgery for tubal pregnancy.

PMID- 9141599
TI  - A new method for measuring menstrual blood loss and its use in screening women
      before endometrial ablation.

PMID- 9141598
TI  - Blood pressure measurement in pregnancy.

PMID- 9141600
TI  - Spectrotemporal and spectral turbulence analysis of the signal-averaged P wave in
      paroxysmal atrial fibrillation.
AB  - Patients with paroxysmal atrial fibrillation (AF) have greater overall P wave
      magnitude than control subjects, but the temporal localization of the increased
      energy is unknown. P wave spectral turbulence has not been investigated in such
      patients, and the optimum methodology for studying P wave signals has not been
      defined. This study, therefore, applied both spectrotemporal and spectral
      turbulence analyses to the signal-averaged P waves of patients with paroxysmal AF
      and to representative control subjects. Group A, 58 persons without
      cardiopulmonary disease (24 patients with paroxysmal AF, 34 control subjects),
      and group B, 57 with such disease (31 patients with paroxysmal AF, 26 control
      subjects), were studied. Spectral analysis was performed on a windowed 64-ms data
      segment that was advanced through the P wave in 2-ms steps. Spectral turbulence
      was measured from differentiated 24-ms data segments, by either cross-correlation
      between adjacent spectra, or differentiation of adjacent spectral coefficients
      over time (SV, spectral velocity). Patients had greater maximum P wave energy
      than control subjects, between 80-150 Hz for group A (means, 0.9 vs 0.7 microV2 x
      s), and 20-150 Hz for group B (means, 22.4 vs 16.3 microV2 x s). Spectral
      velocity was greater in patients with paroxysmal AF than in control subjects in
      both groups (group A: Peak SV, 11.6 vs 7.4 microV2 and group B: Peak SV, 12.0 vs
      7.6 microV2). Increased energy and SV were reported in the central P wave.
      Spectrotemporal analysis suggested abnormal atrial activation in the central P
      wave associated with paroxysmal AF. A localized abnormality in atrial
      electrophysiology may cause the electrogenesis of the arrhythmia.

PMID- 9141601
TI  - Juvenile ECG pattern in adult black Arabs.
AB  - A juvenile electrocardiographic (ECG) pattern is compatible with T wave inversion
      in the precordial leads V1 and V2 or in additional precordial leads to the left
      of V2. Electrocardiographic studies were performed in 48 Semitic Arabs, including
      26 men and 22 women, and in 50 black Arabs (negroid Bedouins), including 22 men
      and 28 women. The subjects ranged in age from 20 to 46 years. The juvenile ECG
      pattern was found in 6 of the 28 black Arab women (21%), but it was not detected
      in the 22 black Arab men or in any Semitic Arabs of either sex. The difference
      between the two female groups was significant (P < .05). Careful interpretation
      of ECG recordings in black Arab women is recommended in order to prevent a
      misdiagnosis of myocardial ischemia or a misreading of T wave inversions related
      to a previous coronary event.

PMID- 9141602
TI  - Increased prevalence of large bites in 12-lead vectorcardiograms of diabetic
      patients.
AB  - The vectorcardiographic (VCG) bites in diabetic patients were compared with those
      in nondiabetic control subjects using automated analysis of the conventional
      electrocardiogram (ECG). A 12-lead ECG was recorded from each of the 154 patients
      with non-insulin-dependent diabetes mellitus and 128 control subjects. The
      orthogonal leads X, Y, and Z were derived from the 12-lead ECG, from which a so
      called 12-lead VCG was calculated for each of the 282 participants. A computer
      based method for the detection and quantification of bites was applied to the 12
      lead VCGs. Bite amplitudes in the horizontal loop had an average of 0.062 +/-
      0.089 mV in the diabetic group, and 0.039 +/- 0.045 mV in the control group (P <
      .01). In the sagittal plane, the mean bite amplitude was also greater in the
      diabetic group than in the control group: 0.095 +/- 0.084 versus 0.069 +/- 0.058
      mV, respectively (P < .01). A bite greater than 0.1 mV in the horizontal or
      sagittal planes was found in 56 diabetic patients (36%) and 27 control subjects
      (21%) with (P < .05) considered significant. In conclusion, the results of this
      study suggest that automated analysis of the 12-lead VCG can be valuable in
      diagnosing diabetic cardiomyopathy.

PMID- 9141603
TI  - Transient disappearance of Q waves of previous myocardial infarction due to
      exercise-induced ischemia of the contralateral noninfarcted myocardium.
AB  - The electrocardiogram (ECG) of a 40-year-old woman with an old inferolateral
      myocardial infarction revealed, in the course of an exercise treadmill/thallium
      test, gradual disappearance of infarctional Q waves, which reappeared gradually
      during recovery from exercise. The patient had evidence of exercise-induced
      myocardial ischemia both by the ECG and by thallium-201 perfusion scintigraphy
      involving several myocardial regions. The temporal association of transient
      disappearance of Q waves with the occurrence of reversible ischemia suggested
      that the latter was instrumental in producing this phenomenon, through a
      transient failure of the ischemic anterior wall to shift the initial
      depolarization forces away from the infarcted inferolateral territory. Further
      evidence for this concept was provided by the case of another patient, a 49-year
      old man who also had an old inferolateral myocardial infarction and whose ECG in
      the course of an exercise treadmill/thallium test did not reveal any changes in
      the infarctional Q waves. In this patient, thallium images showed mild,
      reversible inferolateral myocardial ischemia but a well perfused anterior wall,
      which provided for early depolarization forces (thus Q waves) directed opposite
      to the region of infarcted myocardium.

PMID- 9141604
TI  - Giant negative U waves during acute myocardial infarction and ischemia.
AB  - Giant negative U waves transiently appeared in a patient with acute myocardial
      infarction (AMI). During hospitalization, these giant negative U waves (0.3-0.5
      mV) were observed in leads V2 through V4 of the electrocardiogram (ECG). The
      waves disappeared 10 days after hospitalization, but reappeared during a
      treadmill exercise test 3 weeks after the onset of AMI. The same waves were
      detected again when the patient was admitted for angina pectoris 3 months later.
      Since these giant negative U waves appeared concomitant with myocardial ischemia,
      ischemia seems to be their cause. To our knowledge, there are no previous reports
      on reproducible U waves like those seen in this patient.

PMID- 9141605
TI  - Unusual ECG variations in left-sided pneumothorax.
AB  - A patient with spontaneous left-sided pneumothorax and unusual, phasic voltage
      variations in the electrocardiogram (ECG), which fluctuated depending on
      respiration, was observed. After intercostal tube drainage, these variations
      disappeared. The respiratory changes in the thorax seem to be a cause of these
      ECG findings.

PMID- 9141606
TI  - Effects of lidocaine and diltiazem on recovery of electrophysiologic activity
      during partial reperfusion following severe myocardial ischemia in canine hearts.
AB  - The effects of lidocaine and diltiazem on recovery of electrophysiologic activity
      during partial reperfusion following severe myocardial ischemia were investigated
      in 28 dogs. The left anterior descending artery was ligated, and the distal end
      was connected to the carotid artery. Myocardial ischemia was induced by
      retrograde blood flow for 10 minutes, after which flow-limited reperfusion (30
      60% of the coronary flow before ischemia) was performed. The dogs were divided
      according to the agent administered before ischemia into the following three
      groups: saline (group S, n = 11); lidocaine (group L, n = 8, 0.07 mg/kg/min by
      intravenous drip infusion following 2 mg/kg intravenous injection); and diltiazem
      (group D, n = 9, 0.02 mg/kg/min by intravenous drip infusion. There were no
      significant differences among the three groups in the incidence of ventricular
      tachyarrhythmia, which occurred as ventricular tachycardia (VT) or ventricular
      fibrillation (VF). In each group, the occurrence of VT was frequently preceded by
      delayed potential which was initiated after reperfusion, with depressed
      conduction in the epicardium, suggesting reentry (82%, 96%, and 87%, not
      significant). The determining factors for VT with degeneration into VF were long
      duration of VT in groups S and L (VT with degeneration into VF vs VT without, 1.2
      +/- 0.2 seconds vs 0.6 +/- 0.1 seconds, P < .05, in group S and 11.6 +/- 2.5
      seconds vs 2.2 +/- 0.4 seconds, P < .05, in group L), and decrease in average R-R
      interval during VT in groups L and D (195 +/- 8 ms vs 313 +/- 17 ms, P< .01, in
      group L and 201 +/- 11 ms vs 327 +/- 28 ms, P< 0.01, in group D). In addition,
      occurrence of epicardial electrophysiologic activity with reduced time from onset
      of the QRS complex in the surface electrocardiogram to the onset of the activity
      during VT preceded VF in group L (VT with degeneration into VF vs VT without,
      130.0 +/- 15.1 ms vs 185.8 +/- 21.4 ms, P < .05), while that with prolongation of
      the time had this effect in group D (116.0 +/- 15.7 ms vs 69.0 +/- 10.7 ms, P <
      .05). It is concluded that, even when partial reperfusion is applied, neither
      lidocaine nor diltiazem suppresses VT because neither drug decreases delayed
      potential acting as a triggering factor or suppresses VF, since the alteration of
      the epicardial conductivity during VT can change the VT circuit to a smaller one.

PMID- 9141607
TI  - Ambulatory patient-activated arrhythmia monitoring: comparison of a new wrist
      applied monitor with a conventional precordial device.
AB  - A wrist-applied transtelephonic device (WrTTD) and a precordial (PrTTD) patient
      activated transtelephonic electrocardiographic (ECG) recorder were compared
      objectively (quality of ECG traces) and subjectively (device preference) in a
      prospective randomized crossover study of 24 patients. All underwent
      cardioversion for chronic atrial fibrillation and were then randomized to each
      device for 1 month. The ECG traces were sent weekly with additional traces if
      symptomatic. Self-administered questionnaires were completed after 1 month with
      each device, and the first five telemetered ECG traces for each patient were
      blindly assessed by two experienced cardiologists. Although the QRS complexes
      were smaller with the WrTTD (P < .001), the quality of the traces was similar. In
      particular, there was no significant difference in number of nondiagnostic
      traces, ability to detect atrial activity, degree of baseline fluctuation, or
      amount of artifact. Overall, patients preferred the PrTTD (P = .02). Patients
      found the PrTTD easier to use (P = .007) and were able to apply it more rapidly
      (P = .02). The quality of ECG traces obtained from the upper limbs by using a
      wrist-applied transtelephonic device was concluded to be comparable with those
      obtained by direct precordial application. In order to increase patient
      acceptability of the former, further improvements to simplify its operation are
      necessary.

PMID- 9141608
TI  - Discrepant drug action of disopyramide on ECG abnormalities and induction of
      ventricular arrhythmias in a patient with Brugada syndrome.
AB  - An electrophysiologic study was attempted in a patient who experienced cardiac
      arrest. Programmed electrical stimulation from the right ventricle, without the
      use of any drugs, induced ventricular fibrillation (VF) twice. Disopyramide
      prevented the induction of ventricular arrhythmia by rendering VF to a
      nonsustained polymorphic ventricular tachycardia when administered at 300 mg/day,
      and noninducible at 400 mg/day. However, ST-segment elevation and the rSr'
      pattern in leads V(1-3) characteristic of Brugada syndrome became exaggerated by
      disopyramide. Disopyramide exerted discrepant action on the electrocardiographic
      (ECG) abnormalities and induction of VF in this patient, suggesting the efficacy
      of antiarrhythmic drugs assessed by an electrophysiologic study may be unrelated
      to ECG abnormalities in cases of Brugada syndrome.

PMID- 9141609
TI  - Arrhythmogenic and antiarrhythmic actions of substances of abuse: effects on
      triggered activity.
AB  - Substances of abuse exert adrenergic and/or depressant actions on the cellular
      processes responsible for cytosolic calcium overload. This investigation
      attempted to determine whether substances of abuse, through catechol-mediated
      effects or cellular actions, elicit or inhibit the production of arrhythmias
      caused by delayed afterdepolarizations (DADs) and triggered activity (TA). The
      papillary muscles of rats and Purkinje fibers of dogs were superfused in vitro
      with Tyrode's solution at 37 degrees C. Intracellular microelectrodes were used
      to record membrane potentials. Overdrives failed to induce DADs and TA in the
      canine Purkinje fibers exposed to either Tyrode's solution alone, or containing
      ethanol or harmine. Instead, ethanol and harmine inhibited DADs and TA induced by
      overdrives in the presence of strophanthidin. On the contrary, in the presence of
      acetaldehyde and amphetamine, overdrives did produce TA, which was inhibited by
      propranolol. In conclusion, substances of abuse may either elicit or inhibit the
      production of DADs and TA, depending on the balance between adrenergic and
      depressant actions on the cellular mechanisms responsible for the calcium
      overload of the cytosol.

PMID- 9141610
TI  - Pentavalent antimonial-induced torsade de pointes.
AB  - Unexplained sudden deaths following use of pentavalent antimonial drugs have been
      described, presumably owing to ventricular arrhythmias. A patient is reported
      with QT interval prolongation and syncopal episodes related to torsade de pointes
      following treatment of visceral leishmaniasis with meglumine antimoniate. This is
      the first reported case of documented torsade de pointes following treatment with
      pentavalent antimonial drugs.

PMID- 9141611
TI  - Sustained ventricular tachycardia in cardiac hemochromatosis treated with
      amiodarone.
AB  - Cardiac hemochromatosis can cause heart failure and cardiac arrhythmias. Among
      these arrhythmias, ventricular tachycardia may be resistant to treatment. A case
      of cardiac hemochromatosis complicated with ventricular tachycardia that did not
      respond to intravenous lidocaine, procainamide or propafenone, nor to DC
      cardioversion, was successfully treated with amiodarone. Amiodarone, a class III
      antiarrhythmic drug, may be highly effective in similar cases.

PMID- 9141612
TI  - Computer versus manual measurement of ST-segment deviation.
AB  - Total ST scores (sum of absolute deviations in all 12 electrocardiographic [ECG]
      leads) have been used for research purposes to estimate total ischemic burden and
      to predict reperfusion after thrombolytic therapy. Computerized monitoring
      systems are capable of measuring ST deviation to the 10-microV level, whereas
      humans are incapable of such precise resolution. The purpose of this study was to
      compare computer versus manual ST scores in 12-lead ECGs exhibiting ischemia and
      to compare interrater reliability of manual measurements between two experts. A
      total of 58 subjects with 100 microV or more ST deviation in one or more leads
      during percutaneous transluminal coronary angioplasty balloon inflation were
      selected for analysis. ST measurements were made at J + 80 ms, using the
      isoelectric line as a reference, and summed across all 12 leads. Manual
      measurements were made to a minimum of 50 microV by two independent reviewers
      blinded to the computer scores. Total ST scores were compared using paired t
      tests, and Pearson coefficients were used to test the correlations. A high
      correlation was observed between the manual and computer measurements (r = .96, P
      < .00) and between the two reviewers (r = .96, P < .00). A high degree of
      interrater reliability is possible with manual measurements of ST deviation.
      Computer measurements are consistently greater than manual measurements,
      presumably because humans "round down" to the nearest 50 microV. As such,
      computers may detect ischemia that is missed by humans. However, computer and
      manual measurements of ST deviation should not be mixed when used as a variable
      for research.

PMID- 9141613
TI  - Isolated infarctions of the right ventricle.

PMID- 9141614
TI  - Thrombin receptor-dependent prostaglandin E2 synthesis in hamster fibroblasts:
      synergistic interactions with interleukin-1beta.
AB  - Cellular responses to alpha-thrombin are mediated through a G-protein-coupled
      receptor that undergoes proteolytic cleavage, unveiling a tethered peptide ligand
      with the amino-terminal sequence SFLLRN. The synthetic peptide SFLLRN can mimic
      many of thrombin's actions via directly stimulating the thrombin receptor.
      Thrombin has been implicated in several cellular events associated with tissue
      injury, including fibroblast growth, matrix deposition, and inflammatory
      responses. The role of the thrombin receptor in fibroblast-dependent release of
      the inflammatory mediator prostaglandin E2 was evaluated and compared to its well
      characterized effect on cell proliferation. Both thrombin and SFLLRN stimulated
      [3H]thymidine incorporation into DNA but failed to induce prostaglandin E2
      release from CCL39 cells. The inflammatory cytokine interleukin-1beta synergized
      with thrombin and SFLLRN to induce the release of prostaglandin E2, whereas it
      had no effect on thrombin receptor-mediated DNA synthesis. Interleukin-1beta had
      no direct effects on thrombin receptor-mediated phosphoinositide hydrolysis,
      suggesting that its effects were downstream from early signal transduction
      events. Thrombin and interleukin-1beta together significantly increased the
      expression of prostaglandin H synthase-2 in accordance with the prostaglandin E2
      results. These studies indicate that the fibroblast thrombin receptor
      differentially couples to intracellular signaling pathways leading to distinct
      functional responses and that thrombin receptor-effector interactions could be
      modulated by interleukin-1beta.

PMID- 9141615
TI  - Partial homology of stress glycoprotein GP62 with HSP70.
AB  - Thermotolerance and heat resistance are often associated with elevated levels of
      heat shock proteins (HSPs) and a selective increase in protein glycosylation. In
      the present study, we have characterized heat stress-induced protein
      glycosylation in M21 cells, derived from the rat fibroblast line, Rat-1. M21
      cells are characterized by constitutive overexpression of human HSP70 gene and
      show increased heat resistance without loss of its normal capacity for
      thermotolerance development after heat conditioning (Li et al., 1991, Proc. Natl.
      Acad. Sci. USA 88, 1681-1685). The data presented here show that the elevated
      heat resistance in these cells is associated not only with the constitutive
      overexpression of human HSP70, but also with increased glycosylation of a major
      stress glycoprotein, GP62 (Mr of 62,000). We further purified GP62 by sequential
      preparative isoelectric focusing and two-dimensional isoelectric focusing/SDS
      polyacrylamide gel electrophoresis. The purified protein was digested and
      partially characterized by microsequencing of two peptide fragments, comprising
      of 14-15 amino acids each. These fragments had a 100% sequence homology with
      HSP70 and a 71-100% sequence homology with HSC70 from various species. Western
      blotting using both HSP70 and HSC70 antibodies showed positive reactivity of GP62
      with HSP70. Affinity characterizations showed strong binding of GP62 to wheat
      germ agglutinin and concanavalin A, consistent with the presence of both alpha-D
      mannosyl/glucosyl and N-acetyl-beta-D-glucosylaminyl/glucosamine oligomer
      residues in GP62. These data confirm the glycosylated status of GP62 and indicate
      that GP62 is a heat stress-induced glycoprotein with partial homology to HSP70.

PMID- 9141616
TI  - Bcl-X(L) expression and its downregulation by a novel retinoid in breast
      carcinoma cells.
AB  - We have recently found a novel retinoid, 6-[3-(1-adamantyl)-4-hydroxphenyl]-2
      naphthalene carboxylic acid (CD437), which induces G1 cell cycle arrest and
      apoptosis in human breast carcinoma (HBC) cells (Oncogene 11, 493-504, 1995).
      CD437 downregulates the expression of a number of proteins which antagonize
      apoptosis. bcl-X(L), a homologue of bcl-2, antagonizes apoptosis, while bcl-X(S)
      enhances apoptosis. We have found that estrogen receptor (ER)-negative HBCs
      express higher levels of bcl-X(L) and significantly lower levels of bcl-2 than
      their ER-positive counterparts. Neither cell type expresses bcl-X(S). The
      addition of CD437 (1 microM) results in a fourfold downregulation of bcl-X(L)
      mRNA and protein levels followed by apoptosis in MDA-MB-231 and MDA-MB-468 cells.
      CD437 concentrations as low as 10 nM cause a significant reduction in both bcl-X
      mRNA and bcl-X(L) protein expression. CD437-dependent downregulation of bcl-X
      mRNA and bcl-X(L) protein expression occurs within 24 h of CD437 addition to the
      cells. Retinoic acid does not effect bcl-X mRNA or bcl-X(L) protein expression.
      CD437 is a potent inducer of apoptosis in a number of breast carcinoma cells
      lines and downregulates the expression of a number of proteins which antagonize
      apoptosis.

PMID- 9141617
TI  - Activation-induced expression of human programmed death-1 gene in T-lymphocytes.
AB  - The Programmed Death-1 (PD-1) gene is a member of the immunoglobulin superfamily
      of genes. Murine PD-1 mRNA expression has been shown to correlate with activation
      induced apoptosis in a mouse T-cell hybridoma cell line and in murine thymocytes.
      Here we report that expression of the human homolog, hPD-1, seems to correlate
      with activation of T lymphocytes rather than apoptosis. We observed a time
      dependent upregulation of hPD-1 mRNA and protein levels in Jurkat cells during
      phorbol ester (12-O-tetradecanoylphorbol 13-acetate, TPA)-induced
      differentiation. Human PD-1 protein was also induced during lectin-stimulated
      activation of human peripheral blood mononuclear cells. Additionally, TPA
      stimulation of Jurkat cells induces tyrosine phosphorylation of hPD-1, putatively
      on its cytoplasmic tail signal transduction motif. These data suggest a role for
      hPD-1 during activation and differentiation of T-lymphocytes.

PMID- 9141618
TI  - Telomere-telomere interactions and candidate telomere binding protein(s) in
      mammalian sperm cells.
AB  - We have used fluorescent in situ hybridization to localize telomeres within the
      nuclei of sperm from six mammals (human, rat, mouse, stallion, boar, and bull).
      In minimally swollen sperm of mouse and rat, most of the telomeres are clustered
      within a limited area in the posterior part of nuclei. In sperm of other species,
      telomeres associate into tetrameres and dimers. On swelling of sperm cells with
      heparin/dithiotriethol, telomere associations disperse, and hybridization signals
      become smaller in size and their numbers approach or correspond to the number of
      chromosome ends in a haploid genome. Quantitation of telomere loci indicates that
      dimeric associations are prominent features of mammalian sperm nuclear
      architecture. Higher order telomere-telomere interactions and organization
      develop during meiotic stages of human spermatogenesis. At this stage, telomeres
      also become associated with the nuclear membrane. In an attempt to elucidate the
      molecular mechanisms underlying telomere interactions in sperm, we have
      identified a novel protein activity that binds to the double-stranded telomeric
      repeat (TTAGGG)n. Sperm telomere binding protein(s) (STBP) was extracted from
      human and bull sperm by 0.5 M NaCl. STBP does not bind single-stranded telomeric
      DNA and is highly specific for single base substitutions in a duplex DNA
      sequence. Depending on the conditions of binding, we observed the formation of
      several nucleoprotein complexes. We have shown that there is a transition between
      complexes, which indicates that the slower migrating complex is a multimer of the
      higher mobility one. We propose that STBP participates in association between the
      telomere domains which were microscopically observed in mammalian spermatozoa.

PMID- 9141619
TI  - Target cell-induced calcium signals in human natural killer leukemia cells as
      revealed by confocal fluorescence microscopy.
AB  - The target cell-induced calcium response in natural killer (NK) cells was
      examined using indo-1 (a ratiometric fluorochrome), a newly developed video-rate
      ultraviolet laser-scanning confocal microscope system, and a human NK leukemia
      cell line, YTN. Susceptible target cells (JY cells), but not unsusceptible target
      cells (K562 cells), increased the intracellular calcium concentration ([Ca]i) in
      almost all indo-1-loaded YTN cells with a lag time, although the kinetics of
      increase in [Ca]i differed in individual YTN cells. The increase in [Ca]i was
      completely blocked by 2 mM EGTA and partially (around 50%) blocked by 10 microM
      nicardipine, the extents of inhibition of calcium response correlating well with
      those of inhibition of cytotoxic activity. Thus, the calcium response in YTN
      cells observed in this study may constitute a critical step in the manifestation
      of cytotoxic activity.

PMID- 9141620
TI  - Antibodies specific to the plasma membrane of rat lung microvascular endothelium.
AB  - The highly purified, luminal domain of rat lung endothelial plasma membranes was
      used as an immunogen to obtain monoclonal antibodies to the endothelial cell
      surface. The procedure was highly efficient, yielding antibodies which recognize
      three seemingly novel endothelial integral membrane glycoproteins of molecular
      weights of 170, 114, and 95 kDa, respectively. By immunofluorescence, two of
      these antigens (170 and 95 kDa) appeared to be uniquely expressed by the lung
      microvascular endothelium. The third one, the 114-kDa polypeptide, was detected
      in the continuous endothelium of the lung, but also in the fenestrated endothelia
      of pancreas, intestinal villi, and kidney peritubular capillaries. Partition in
      Triton X-100-soluble and -insoluble plasmalemmal components suggests that two of
      these novel endothelial antigens (170 and 114 kDa) are specific for the plasma
      membrane proper only, while that of 95 kDa is present both in the caveolae and on
      the rest of the cell surface.

PMID- 9141621
TI  - Expression analysis of mortalin, a unique member of the Hsp70 family of proteins,
      in rat tissues.
AB  - We have investigated the expression of mortalin in rat tissues by Northern
      analysis, RNA in situ hybridization, and immunohistochemical studies. By Northern
      assay, the highest level of expression was detected in brain, heart, and skeletal
      muscle followed by lung, liver, and kidney, and the least level of expression was
      detected in testis and spleen. RNA in situ and immunohistochemical studies showed
      that mortalin expression is significantly higher in upper nondividing layers than
      in the lower basal layers of skin, in neurons and nerve fibers than in
      surrounding glial cells in brain, in cardiomyocytes than in nonmyocytes in heart,
      and in interstitial secretory tissue than in germinating follicles in ovary. Such
      tissue- and cell-specific expression patterns of mortalin coordinates with its
      earlier reported antiproliferative function in normal cells. However, a
      deregulation of the expression is observed in rat brain tumor along with the
      detection of nonpancytosolic mortalin in rat glioma cell line C6. The study
      suggests that mortalin is involved in pathways that regulate division capacities
      of cells in vivo.

PMID- 9141622
TI  - Variation of heat shock protein 70 through the cell cycle in HL-60 cells and its
      relationship to apoptosis.
AB  - Cells respond to a heat shock by synthesizing heat shock proteins, which help to
      protect the cells from further heating. Recent results indicate that heat shock
      protein 70 (hsp70) may help to protect cells from apoptosis. We have used flow
      cytometry to investigate the relationship between constitutive and inducible
      hsp70 and apoptosis through the cell cycle in HL-60 cells. Specific antibodies
      were used to measure hsp70 in cells costained with propidium iodide. In separate
      samples apoptosis was measured using the TdT assay. The apoptotic cells have a
      subdiploid DNA content, which allows them to be identified also in the bivariate
      histograms of heat shock protein vs DNA content. After HL-60 cells were heated at
      45.0 degrees C for 7.5 min and incubated for various times at 37 degrees C, many
      of them underwent apoptosis. The level of inducible hsp70 (hsp72) was lower in
      the apoptotic cells than in the nonapoptotic population, but constitutive hsp70
      (hsp73) was the same in both populations. Pretreatment with sodium vanadate
      increased the fraction of apoptotic cells twofold, slightly increased the level
      of hsp72 in the nonapoptotic cells, but did not affect hsp73. These results
      suggest that hsp72, but not hsp73, is involved in the development or prevention
      of apoptosis.

PMID- 9141623
TI  - Translocation of cdk2 to the nucleus during G1-phase in PDGF-stimulated human
      fibroblasts.
AB  - We studied the subcellular distribution of cdk2 in synchronized, PDGF-stimulated
      human fibroblasts (FH109). After contact inhibition and serum depletion, more
      than 95% of FH109 cells were arrested in G0/G1-phase. PDGF-AB led to a 16-fold
      increase in proliferation compared with untreated cells. Cell cycle progression
      was studied by flow cytometric analysis, [3H]thymidine incorporation, and
      phosphorylation of the retinoblastoma gene product, pRB. Using Western blot
      analysis after subcellular fractionation, we revealed that after PDGF stimulation
      the phosphorylated (Thr 160), i.e., activated, form of cdk2 (33 kDa) first
      appeared in the nucleus at late G1-phase and persisted throughout until to the
      end of S-phase. Since cdk2 was not synthesized de novo, and the amount of
      inactive cdk2 (35 kDa) remained constant in the nucleus, we suggested a
      translocation from the cytosol to the nucleus in late G1. Using
      immunofluorescence techniques, we detected a diffuse staining in quiescent cells.
      Starting at late G1-phase, cdk2 immunoreactivity was concentrated to the nucleus
      while immunoreactivity in the cytosol disappeared. We therefore draw the
      conclusion that cdk2 is translocated from the cytosol into the nucleus in late G1
      phase. Since protein levels and activity of cdk7, which is the catalytic subunit
      of cdk-activating kinase (CAK) phosphorylating cdk2, remained constant throughout
      the cell cycle, CAK activity might therefore be regulated by the availability of
      its substrate cdk2.

PMID- 9141624
TI  - Regulation of parathyroid hormone-related protein secretion and mRNA expression
      in normal human keratinocytes and a squamous carcinoma cell line.
AB  - Parathyroid hormone-related protein (PTHrP) has been identified as a causative
      factor in the pathogenesis of humoral hypercalcemia of malignancy (HHM). The
      regulation and mechanisms of PTHrP secretion in most normal and malignant cells
      are unknown. PTHrP secretion, mRNA expression, and transcription were measured in
      neoplastic human squamous carcinoma cells (A253) and normal human foreskin
      keratinocytes (NHFK) by radioimmunoassay, RNase protection assay, and transient
      transfections of the 5'-flanking region of human PTHrP in a luciferase expression
      vector. Mechanisms of PTHrP secretion were investigated using chemicals
      (monensin, colchicine, cytochalasin B, guanosine 5'-[gamma-thio]triphosphate
      (GTPgammaS)) that interfere with or facilitate intracellular transport. Monensin
      inhibited PTHrP secretion in both NHFK and A253 cells. Ultrastructurally,
      monensin caused dilatation of rough endoplasmic reticulum and the formation of
      numerous cytoplasmic secretory vacuoles in both cell lines. Colchicine decreased
      PTHrP production in NHFK cells and stimulated PTHrP production and mRNA levels in
      A253 cells. Colchicine also stimulated transcription of the PTHrP-luciferase
      reporter gene. Cytochalasin B stimulated PTHrP secretion and mRNA expression in
      A253 cells, but had no effect in NHFK cells. GTPgammaS had no effect on PTHrP
      secretion in either cell line. It was concluded that PTHrP secretion is dependent
      on the constitutive movement of secretory vesicles to the cytoplasmic membrane
      and regulation of PTHrP secretion and mRNA expression are altered in squamous
      carcinoma cells compared to normal human keratinocytes in vitro.

PMID- 9141625
TI  - Induction of erythroid gene expression by microcell fusion.
AB  - The molecular events which underlie lineage commitment and differentiation in
      hematopoietic cells are still incompletely understood. Microcell fusion is a
      versatile technique which has been utilized in characterizing and mapping genes
      involved in tumor suppression, cell senescence, and certain aspects of
      differentiation. Microcell fusion has the potential to contribute to the
      understanding of hematopoietic differentiation; however, application of this
      technique is limited by the need to use adherent cells as microcell donors, by
      the need to tag candidate chromosomes with a selectable marker, and by the need
      for prolonged selection of fused cells prior to characterization of their
      phenotype. We developed a modified technique of microcell fusion using square
      wave electroporation, which allows higher efficiency fusion than polyethylene
      glycol fusion. By using cross-species fusion and species-specific PCR primers, we
      were able to detect new gene induction events 48 h after microcell fusion. To
      study erythroid gene expression, we fused microcells from human erythroid K562
      cells to murine B-lymphoid SP-2 cells. We found that microcell fusion induced the
      nonerythroid recipient cells to express alpha-globin mRNA in a dose-dependent
      manner. They also expressed RNA for beta-globin, GATA-1, and NF-E2. In contrast,
      there was no expression of heart- or liver-specific genes. We conclude that
      microcells from erythroid cells contain all the information necessary to induce
      expression of multiple erythroid genes. Analysis of the components of the
      microcells responsible for this new gene induction may allow the characterization
      of cellular factors responsible for erythroid-specific gene expression.

PMID- 9141626
TI  - The mature osteoblast phenotype is characterized by extensive plasticity.
AB  - While both morphological and biochemical-molecular attributes demarcate
      differentiation stages in specific cell and tissue types, what constitutes
      necessary and sufficient expression to define particular cell types is not always
      known. For example, mature osteoblasts (OBs) are defined morphologically as the
      cuboidal, biosynthetically active, basophilic cells residing on bone surfaces and
      responsible for the deposition of osteoid matrix. However, several recent
      observations suggest that not all mature OBs are identical. To explore further
      the validity of the hypothesis that heterogeneity of phenotype exists among
      mature OBs, we grew fetal rat calvaria cells in vitro at low density under
      conditions in which bone nodules form and mineralize in isolation of other
      contaminating cell and colony types. Cells resident in mature OB colonies, i.e.,
      those comprising mainly cuboidal cells associated with an osteoid matrix that had
      begun to mineralize, were analyzed in situ for protein expression by
      immunocytochemistry with antibodies against collagen type I, alkaline
      phosphatase, osteopontin, bone sialoprotein, and osteocalcin. Consistent with the
      expected phenotype of mature OBs, many OBs expressed high levels of all of these
      markers, but strikingly even adjacent morphologically indistinguishable cuboidal
      OBs had differences in protein expression, especially in relation to osteopontin,
      bone sialoprotein, and osteocalcin expression. Double-labeling with Hoechst 33258
      and osteocalcin indicated that the variation in antibody labeling
      intensity/protein expression appeared independent of a variation in cell cycle.
      To further ascertain the extent of this heterogeneity, 20 single cells were
      micromanipulated from colonies and subjected to poly(A)-PCR to analyze the
      simultaneous coexpression profiles of the same five markers analyzed by
      immunocytochemistry and two other markers, the OB-osteocyte transition marker E11
      and the parathyroid hormone/parathyroid hormone-related protein receptor.
      Notably, the repertoire of genes expressed and their levels of expression varied
      markedly in individual OBs. The observed heterogeneity suggests that the mature
      OB phenotype is not a single unique phenotype but rather encompasses a flexible
      pattern of expression from the repertoire of OB-associated markers.

PMID- 9141627
TI  - An in vitro force measurement assay to study the early mechanical interaction
      between corneal fibroblasts and collagen matrix.
AB  - An in vitro force measurement assay has been developed to quantify the forces
      exerted by single corneal fibroblasts during the early interaction with a
      collagen matrix. Corneal fibroblasts were sparsely seeded on top of collagen
      matrices whose stiffness was predetermined by micromanipulation with calibrated
      fine glass microneedles. The forces exerted by individual cells were calculated
      from time-lapse videomicroscopic recordings of the 2-D elastic distortion of the
      matrix. In additional experiments, the degree of permanent reorganization of the
      collagen matrices was assessed by lysing the cells with 1% Triton X-100 solution
      at the end of a 2-hour incubation and recording the subsequent relaxation. The
      data suggest that a cell can exert comparable centripetal force during either
      extension of a cell process or partial retraction of an extended pseudopodia. The
      rates of force associated with pseudopodial extension and partial retraction were
      0.180 +/- 0.091 (x 10(-8)) N/min (n = 8 experiments) and 0.213 +/- 0.063 (x 10(
      8)) N/min (n = 8 experiments), respectively. Rupture of pseudopodial adhesion
      associated with cell locomotion causes a release of force on the matrix and a
      complete recoil of the pseudopodia concerned; a simultaneous release of force on
      the matrix was also observed at the opposite end of the cell. Lysis of cells
      resulted in 84 +/- 18% relaxation of the matrix, suggesting that little permanent
      remodeling of matrix is produced by the actions of isolated migrating cells.

PMID- 9141628
TI  - Human fibroblasts bind directly to fibrinogen at RGD sites through integrin
      alpha(v)beta3.
AB  - Fibroblast migration into the blood clot initially filling a wound requires close
      interaction between fibroblasts and the matrix of the fibrin clot. However, very
      little is known about the specific receptor-ligand interactions that mediate
      fibroblast attachment to fibrin. Using an attachment assay developed to measure
      even relatively weak interactions, we demonstrate here that normal human dermal
      fibroblasts can attach to substrates coated with fibrinogen, fibrin, or the
      fibrinogen breakdown product I-9D. Fibroblast attachment to these ligands did not
      require the presence of fibronectin on the cell surface or as a component of the
      substrate. Cells treated with cycloheximide and monensin, to limit the synthesis
      and secretion of endogenous fibronectin, attached as well as untreated cells. The
      synthetic peptide GRGDS inhibited adhesion to fibrinogen, fibrin, and fibrinogen
      I-9D by about 60%, while the control peptide GRGES had no substantial effect. We
      conclude that attachment to these ligands is mediated at least partially by
      direct interactions between the substrates and one specific receptor, the
      integrin alpha(v)beta3. Affinity chromatography demonstrated that alpha(v)beta3
      from detergent lysates of fibroblasts bound to a fibrinogen matrix and was eluted
      with EDTA. Furthermore, antibodies against the alpha(v)beta3 complex or against
      the alpha(v) subunit inhibited fibroblast attachment to fibrinogen and fibrin by
      50-70%. An inhibitory antibody against the integrin beta1 subunit had no effect.
      The observation that integrin antagonists could not produce complete inhibition
      suggests that there may be other fibroblast cell surface proteins that can bind
      directly to fibrinogen.

PMID- 9141629
TI  - Strain reorganizes focal adhesions and cytoskeleton in cultured airway smooth
      muscle cells.
AB  - Abnormal mechanical stress on pulmonary structures is associated with increased
      airway resistance and impaired gas exchange as a result of increased airway
      smooth muscle (ASM) deposition. Using an in vitro system with cultured ASM cells,
      we have demonstrated that cyclic deformational strain increases ASM cellular
      myosin and myosin light chain kinase. To determine if these contractile protein
      increases were accompanied by ultrastructural changes in cells indicating
      phenotypic modulation, cells subjected to strain were compared to cells grown
      under static conditions by transmission electron microscopy (TEM) and fluorescent
      staining. The strained ASM cells oriented perpendicular to the strain direction
      were more elongated and contained more actin stress fibers than identical cells
      grown under physically static conditions. The stress fiber bundles were thicker
      and reorganized parallel to the long axis of the cell. Marked increases in the
      numbers and lengths of focal adhesions between the cell membrane and the
      substratum were found by both TEM and immunostaining for talin. Mechanical strain
      thus increases organization of cytoskeletal elements in cultured ASM cells.
      Similar effects in vivo may serve to promote the expression of the contractile
      phenotype of cultured ASM cells independent of other in vivo factors and alter
      cell contractility. Increased organization of cytoskeletal elements might also
      increase the efficiency of signal transduction from the extracellular matrix into
      the cell interior.

PMID- 9141630
TI  - Glycerol and polylysine synergize in their ability to rupture vesicular
      membranes: a mechanism for increased transferrin-polylysine-mediated gene
      transfer.
AB  - The presence of about 1.2 M glycerol during transfection with DNA/transferrin
      polylysine and DNA/polylysine complexes dramatically increases transgene
      expression in a variety of cell types, provided that the complexes have an excess
      of polylysine. We have characterized this phenomenon using a human melanoma cell
      line (H225). The addition of 1.2 M glycerol to the transfection medium has no
      influence on the internalization of DNA complexes or on the promoter activity
      used to direct reporter gene expression. Neither prenor postincubation of the
      cells with glycerol results in a notable increase in transgene expression.
      Bafilomycin A1 and chloroquine, two drugs affecting the endosomal pathway, both
      influenced transgene expression, indicating that glycerol acts on internal
      vesicles. Glycerol and polylysine synergized in their ability to lyse
      erythrocytes as well as internal vesicles (microsomes) isolated from H225 cells,
      indicating that the glycerol effect is due to a labilization of vesicular
      membranes, which facilitates membrane disruption by polylysine. Our current model
      suggests that the excess of polylysine in the DNA complexes disrupts vesicular
      membranes in the presence of glycerol, thus allowing the release of DNA complexes
      into the cytoplasm.

PMID- 9141631
TI  - Three-dimensional visualization of the route of protein import: the role of
      nuclear pore complex substructures.
AB  - The three-dimensional localization of nucleoplasmin and wheat germ agglutinin
      (WGA) at the nuclear envelope of Xenopus oocytes is demonstrated by
      microinjecting protein coated gold colloids and examining their distribution
      using both stereo transmission electron microscopy and field emission in-lens
      scanning electron microscopy. Localization of many WGA gold particles and
      nucleoplasmin gold particles at the same nuclear pore complex (NPC) following
      coinjection is demonstrated. Binding of the WGA gold in the central region of the
      NPCs appears to form a barrier, preventing the import of nucleoplasmin gold, and
      includes central localization along radial "tracks" which correspond to the
      internal filaments connecting the cytoplasmic ring and the central region of the
      NPC. We suggest that these filaments may in some way be involved in opening and
      closing of the central channel of the NPC for transport. Transport of
      nucleoplasmin through the central region of the NPCs appears to be in "single
      file" regardless of the size of the colloidal gold, and distribution into the
      nucleoplasm appears to be through the basket rings with no association of the
      nucleoplasmin gold with the basket filaments being observed.

PMID- 9141632
TI  - Temporal position of G1 arrest in normal human fibroblasts after exposure to
      gamma-rays.
AB  - G1 phase cell cycle arrest after exposure to ionizing radiation has been
      documented in cells with wild-type p53. The temporal location of this arrest
      within G1 phase, however, has not been determined. We have now used flow
      cytometric analysis of bromodeoxyuridine (BrdUrd)-labeled cells to obtain further
      information about the location of the G1 phase radiation checkpoint. Human
      fibroblasts were irradiated with gamma-rays and treated with colcemid to stop
      unlabeled G2 cells from entering the G1 phase. Analysis of BrdUrd incorporation
      revealed that 73% of G1 phase human lung fibroblasts remain in G1 phase after
      exposure to gamma-rays, thereby placing the G1 radiation checkpoint near the end
      of G1 phase. The location of the radiation checkpoint correlates with the
      reported increased expression of cyclin E, increased cyclin E/cdk2 kinase
      activity, and hyperphosphorylation of pRb in proliferating human fibroblasts.

PMID- 9141633
TI  - Heregulin degradation in the absence of rapid receptor-mediated internalization.
AB  - Heregulin receptors are unable to mediate the rapid internalization of bound
      ligand as demonstrated in cells transfected with chimeric or wild-type ErbB-2, 
      3, or -4 receptors (Baulida et al., 1996, J. Biol. Chem. 271, 5251-5257; Pinkas
      Kramanski et al., 1996, EMBO J. 15, 2452-2467). This observation is now extended
      to include mammary carcinoma cell lines (SK-BR-3 and MDA-543) which express
      endogenous ErbB-2 and ErbB-3 receptors. Also, the fate of receptor-bound
      heregulin is examined. While receptor-bound heregulin is not rapidly
      internalized, the ligand is subject to a slow process of inactivation and
      degradation, which requires heregulin incubation at 37 degrees C with cells that
      express heregulin receptors. The degradation of heregulin is blocked to a
      significant extent by chloroquine, an inhibitor of endosome fusion with
      lysosomes, indicating that heregulin is slowly internalized and degraded.
      However, this process is not sufficiently rapid to produce ligand-dependent down
      regulation of heregulin receptors.

PMID- 9141634
TI  - Peripheral framework of carrot cell nucleus contains a novel protein predicted to
      exhibit a long alpha-helical domain.
AB  - A monoclonal antibody, CML-1, raised against carrot (Daucus carota L.) nuclear
      matrix proteins selectively labeled the nuclear periphery of carrot protoplasts
      when visualized by confocal and electron microscopy. To identify the constituent
      proteins of higher plant cells structurally homologous to the vertebrate nuclear
      lamina, we cloned overlapping cDNAs partially encoding a CML-1-recognized protein
      and determined the entire sequence including the open reading frame. When the
      deduced amino acid sequence was compared with other known protein sequences
      contained in major databases, no protein was found to show high sequence identity
      across the whole region of the protein, while the partial sequence showed strong
      similarities with myosin, tropomyosin, and some intermediate filament proteins.
      The protein, designated NMCP1, had an estimated molecular mass of 133.6 kDa and
      showed three characteristic domains. The central domain contains long alpha
      helices exhibiting heptad repeats of apolar residues, demonstrating structural
      similarity to that of filament-forming proteins. The terminal domains are
      predominantly nonhelical and contain potential sequence motifs for nuclear
      localization signals. NMCP1 has many recognition motifs for different types of
      protein kinases, including cdc2 kinase and PKC. These results suggest that NMCP1
      protein forms coiled-coil filaments and is a constituent of the peripheral
      architecture of the higher plant cell nucleus.

PMID- 9141635
TI  - The nucleoporin CAN/Nup214 binds to both the cytoplasmic and the nucleoplasmic
      sides of the nuclear pore complex in overexpressing cells.
AB  - CAN/Nup214, an essential component of the vertebrate nuclear pore complex (NPC),
      is required for proper cell cycle progression and nucleocytoplasmic transport. It
      is a member of the FG-repeat-containing family of nucleoporins and has been
      localized to the cytoplasmic face of the NPC. Indirect immunofluorescence studies
      with specific antibodies have shown that moderate overexpression of human CAN in
      HeLa cells causes an increase in CAN/Nup214 levels at the nuclear envelope. Here,
      we demonstrate that in such HeLa cells, CAN/Nup214 does not localize exclusively
      to the cytoplasmic side of the NPC. Cryosections, stained with CAN-specific
      antibodies and examined by electron microscopy, showed that about one-third of
      the gold-labeled NPCs were decorated at the cytoplasmic face and the remaining
      two-thirds at the nucleoplasmic face. These data indicate that both the
      cytoplasmic fibrils and the nuclear basket of the vertebrate NPC contain specific
      binding sites for either CAN/Nup214 or for its interacting proteins, Nup88 and
      hCRM1. Thus, it is conceivable that CAN/Nup214 functions in nucleocytoplasmic
      transport at both faces of the NPC.

PMID- 9141637
TI  - The correlates of left-handedness: moderating variables in the epidemiology of
      left-handedness.

PMID- 9141636
TI  - Permeabilization of mammalian cells to proteins: poliovirus 2A(pro) as a probe to
      analyze entry of proteins into cells.
AB  - Two hybrid protein molecules containing the poliovirus protease 2A (MBP-2A(pro))
      (maltose-binding protein-2A(pro) and MBP-Pseudomonas exotoxin A-2A(pro)) have
      been constructed and purified. Both hybrid proteins efficiently cleave the
      translation initiation factor eIF-4G when they are co-internalized into cells
      with adenovirus particles. Almost no intact eIF-4G can be detected in cells
      incubated with these proteins following this method. Reovirus infectious subviral
      particles also promote the delivery of MBP-2A(pro) into cells, although less
      efficiently than adenovirus particles. None of the other methods employed to
      permeabilize cells to MBP-2A(pro) achieves the degree of eIF-4G cleavage observed
      with adenovirus particles. By comparison about 30% of cells electroporated with
      MBP-2A(pro) still contain intact eIF-4G. More drastic electroporation conditions
      lead to a significant decrease of cell survival. Osmotic lysis of pinocytic
      vesicles resulted in 30% of the eIF-4G being cleaved in cells treated in
      suspension. Delivery of MBP-2A(pro) by pH-sensitive liposomes leads to poor
      hydrolysis of eIF-4G. Taken together our results indicate that permeabilization
      of cells with adenovirus particles is the most efficient method for introducing
      MBP-2A(pro) into cells.

PMID- 9141638
TI  - The epidemiology of left-handedness in a hospital population.
AB  - PURPOSE: We evaluated the association between left-handedness (LH) and age,
      education, cigarette smoking, alcohol consumption, and disease status in a case
      control study of 8801 hospitalized patients with cancer and those with other
      conditions. METHODS: Subjects were interviewed in person using a structured
      questionnaire that contained detailed sections of lifestyle behaviors. RESULTS:
      The overall prevalences of LH were 7.6% among men and 6.5% among women. Among
      both sexes LH declined with increasing age (P < 0.05). After adjustment for age,
      the following associations were observed. Men had a higher risk of LH than women.
      The prevalence of LH was lower in ever-married subjects compared with never
      married subjects (odds ratio [OR] for men, 0.7; 95% confidence intervals [CI],
      0.5-0.9; for women, OR, 0.5; 95% CI, 0.3-0.9). Among men, the prevalence of LH
      was not associated with race, years of education, smoking status, or levels of
      alcohol consumption. The risk of LH was elevated in men diagnosed with fractures
      as compared with all other male patients (OR, 2.4; 95% CI, 1.3-6.7). Among women,
      LH was not associated with race, smoking, or hormonal and reproductive factors,
      but LH was more common among female high-school and college graduates and among
      self-reported alcoholics. The odds ratio of LH was significantly lower in women
      with breast cancer (OR, 0.3; 95% CI, 0.1-0.7). CONCLUSIONS: The increased risk of
      serious injuries in LH is not a result of higher alcohol use. Handedness might be
      an important factor in the safe use of industrial equipment.

PMID- 9141639
TI  - Evaluating the relationships among maternal reproductive history, birth
      characteristics, and infant leukemia: a report from the Children's Cancer Group.
AB  - PURPOSE: Specific events in the mother's reproductive history and certain birth
      characteristics have been associated with childhood leukemia. Few studies have
      explored these associations specifically in infants. METHODS: The Children's
      Cancer Group (CCG) conducted three separate case-control studies of childhood
      leukemia that involved similar methodologies and data collection. Data from
      interviews of the mothers of a total of 303 children diagnosed with leukemia at 1
      year of age or younger and their matched controls (n = 468) were available from
      the three studies. These data included maternal reproductive history
      (stillbirths, abortions, and miscarriages) and certain birth characteristics of
      the index child. RESULTS: Compared with controls, cases were significantly more
      likely to be female (P < 0.01) and were more often heavier at birth (particularly
      cases diagnosed after 6 months of age (odds ratio, 4.18; 95% confidence interval,
      1.75-10.02)). Overall, there were no statistically significant differences
      between cases and controls in regard to maternal report of any type of previous
      fetal loss. Finally, being a later-born child was associated with an increased
      risk of acute myeloid leukemia but not of acute lymphoblastic leukemia.
      CONCLUSIONS: The relationships among birthweight, prior fetal loss, and risk of
      infant leukemia appear to be complex. Further studies of infant leukemia that
      incorporate molecular as well as epidemiologic data may help to elucidate these
      differences.

PMID- 9141640
TI  - Intermittent claudication in 8343 men and 21-year specific mortality follow-up.
AB  - PURPOSE: As Western populations live longer, peripheral vascular disease will
      become a greater individual and public health problem. Therefore, the long-term
      natural history of intermittent claudication (IC) needs further delineation. The
      study objective was to describe the 21-year mortality and relative risk for cause
      specific mortality for subjects with incident IC. METHODS: The subjects were 8343
      Israeli male governmental employees aged 40-65 years who were free of coronary
      heart disease and symptomatic peripheral vascular disease in 1963. These men were
      followed for 21 years to measure differences in mortality between those who did
      and did not develop incident IC. Incident IC was diagnosed in 1965 and 1968 by
      the London School of Hygiene IC Questionnaire. All other cardiovascular disease
      risk factors were measured by standardized and validated procedures. Cause
      specific mortality through 1986 was determined through death certificates from
      the Israeli Mortality Register. RESULTS: A total of 360 men with IC and 7983
      symptom-free men were followed for survival from 1965 to 1986; 159 men with IC
      (44%) and 2330 symptom-free men (29%) died. For total mortality, the Kaplan-Meier
      21-year survival probabilities were 56% for IC and 71% for symptom-free men (P <
      0.0001 for the entire 21-year survival difference between the two groups). For
      coronary heart disease (CHD), stroke, and other causes of death, the survival
      probabilities for men with IC and symptom-free men were, respectively: 85% vs.
      90%, 89% vs. 97%, and 79% vs. 83% (P = 0.0004; P < 0.0001; and P = 0.007,
      respectively, for the entire 21-year survival difference between the two groups).
      Cox's proportional hazards model was used to control confounding from incident
      myocardial infarction and angina through 1968, as well as for demographic,
      physiologic, psychosocial, and other cardiovascular disease risk factors. The 21
      year adjusted all-cause mortality relative risk for IC was 1.50 (95% confidence
      interval (CI), 1.28-1.77). For stroke deaths the relative risk was 2.76 (95% CI,
      1.89-4.02). For stroke mortality, IC was the third strongest predictor of death
      after elevated systolic blood pressure and increasing age. Incident IC had a
      relative risk of CHD deaths of 1.31, but it was not statistically significant (P
      = 0.08; 95% CI, 0.97-1.77). IC was not statistically significantly related to
      other causes of death (P = 0.10) after adjustment for covariates. CONCLUSIONS: IC
      is strongly predictive of long-term cerebrovascular disease mortality among men.
      Incident IC is a stronger indicator of cerebrovascular than of CHD death.

PMID- 9141641
TI  - A nested approach to evaluating dose-response and trend.
AB  - PURPOSE: Conventional dose-response and trend analysis fits either a linear or
      categorical logistic model and tests the resulting coefficients. These analyses,
      however, are based on implausible assumptions. METHODS: We present an alternative
      approach that uses likelihood ratio tests to compare nested regression models and
      determine when a model is rich enough to capture the data trends. RESULTS: For
      illustration, we apply this approach to data on diet and colorectal polyps.
      CONCLUSIONS: Comparison of linear and quadratic spline logistic models indicates
      that the conventional approach of using only a linear logistic model would not
      appropriately describe the association between intake of fruits and vegetables
      and colorectal polyps in our data. Graphical checking further supports this
      conclusion.

PMID- 9141642
TI  - The effect of nonresponse on estimation of relative risk in a case-control study.
AB  - PURPOSE: Although it is understood that low response rates can bias a study's
      results and that follow-up can increase response rates, the effect of follow-up
      on the odds ratio estimates in a case-control study is not obvious. METHODS: We
      used the data from a case-control study of renal cell carcinoma conducted in
      Ontario. Information on risk factors was collected with a mailed questionnaire;
      the number of telephone or mail follow-ups attempted was recorded. Sex, age
      group, residence, and follow-up method were known for all cases and controls.
      RESULTS: Cases, women, subjects under age 60, subjects living outside of Toronto,
      and subjects with telephone follow-up were all more likely to be respondents.
      This pattern of response did not bias the odds ratio estimates. Over all
      categories of follow-up intensity, the odds ratio estimates for the risk factors
      varied little. For example, the odds ratio estimate for ever smoking cigarettes
      ranged from 1.94 to 2.01 for males and from 2.27 to 1.80 for females.
      CONCLUSIONS: The data indicate that the substantive conclusions of the study
      would not have changed if response rates had been lower. There is a suggestion,
      however, that the odds ratios for smoking by men may be overestimated.

PMID- 9141643
TI  - Predictors of misclassification of Hispanic ethnicity in a population-based
      cancer registry.
AB  - PURPOSE: Hispanic ethnicity is often used as a category for calculating
      population-based rates or assessing risk of epidemiologic studies. However,
      ethnic misclassification can lead to false conclusions unless the extent of
      misclassification and the characteristics of those misclassified are understood.
      METHODS: This study explored determinants of ethnic misclassification in a sample
      of 1154 cancer cases in the San Francisco-Oakland cancer registry, where ethnic
      classification is based on surname or medical record report. We compared the
      following: correctly classified Hispanics, persons classified as Hispanic who
      self-identified as non-Hispanic, and persons classified as non-Hispanic who self
      identified as Hispanic. RESULTS: Among men classified as Hispanic, those most
      likely to self-identify as non-Hispanic did not speak Spanish, had non-Spanish
      surnames, and were recent immigrants. Women misclassified as Hispanic did not
      speak Spanish or have Spanish maiden names, nor did they have mothers with
      Spanish maiden names. Persons who called themselves Hispanic, but were
      misclassified by the registry, were likely to be non-Spanish speaking college
      education males. CONCLUSIONS: Researchers using ethnicity should be aware of how
      ethnicity was determined and how this classification may bias or confound their
      results.

PMID- 9141644
TI  - Urban and rural traumatic brain injuries in Colorado.
AB  - PURPOSE: The purpose of this study was to compare and contrast the epidemiology
      of traumatic brain injury among urban and rural residents of Colorado. METHODS:
      Cases of traumatic brain injury (ICD 800, 801, 803, 804, 850-854) for 1991 and
      1992 from the Colorado surveillance system of hospitalized and fatal traumatic
      brain injuries were used. Urban cases resided in counties designated by the U.S.
      Census Bureau as metropolitan statistical areas (MSA). Rural cases were divided
      into two groups: "rural, nonremote," if the country of residence was adjacent to
      an MSA county or if it had a population of 2500, and "rural, remote," if not.
      RESULTS: Average annual age-adjusted rates of hospitalized and fatal traumatic
      brain injury varied significantly from 97.8 per 100,000 population for the most
      urban group to 172.1 per 100,000 population for the residents of rural, remote
      counties. Similarly, total mortality ranged from 18.1 per 100,000 population
      among residents of the most urban counties to 33.8 among residents of rural,
      remote counties. Prehospital mortality ranged from 10.0 to 27.7 traumatic brain
      injuries per 100,000 population. CONCLUSIONS: These results provide justification
      for expanding efforts to prevent traumatic brain injury to include the small, but
      high-risk group of residents in rural areas.

PMID- 9141645
TI  - Major depression and all-cause mortality among white adults in the United States.
AB  - PURPOSE: Depression is the most common psychiatric illness affecting adults.
      Despite the importance of a potential link between major depression and
      mortality, research has been surprisingly sparse. METHODS: Information on 57,897
      white adults aged 25 years and older who were included in the mental health
      supplement of the 1989 National Health Interview Survey was linked with the
      National Death Index to examine the relationship of major depression to
      mortality. Death status was obtained through December 1991. Sex-specific hazard
      rate ratios for mortality were calculated by Cox proportional hazards regression
      and Poisson regression to adjust for potential confounders (age, education,
      marital status, body mass index, and whether the target subject or a family
      member completed the survey about the subject). RESULTS: Major depression was
      reported for 223 (0.8%) of 27,345 men and 392 (1.3%) of 30,552 women. During the
      2.5-year follow-up, death certificate data were obtained for 848 (3.1%) men and
      651 (2.1%) women. The adjusted hazard rate ratios for all-cause mortality
      associated with major depression were 3.1 (95% confidence interval; 2.0-4.9) for
      men and 1.7 (95% confidence interval; 0.9-3.1) for women. CONCLUSIONS: These
      results suggest that major depression increases risk of all-cause mortality,
      particularly among men. Further research is needed to explain the mechanism.

PMID- 9141646
TI  - Risk of Alzheimer's disease among elderly patients with anemia: population-based
      investigations in Olmsted County, Minnesota.
AB  - PURPOSE: To evaluate the association, if any, between Alzheimer's disease (AD)
      and anemia among the elderly. METHODS: Both case-control and cohort methodologies
      were used to evaluate this association. The case-control study included all
      incident cases of AD whose onset occurred during 1980-1984 in Rochester, MN (n =
      302). An age- and gender-matched control was selected from among Rochester
      residents seen for care at Mayo Clinic during the year of onset of the case. All
      community medical records for cases and controls were reviewed to identify women
      with hemoglobin levels of < 12 g/dL and men with hemoglobin levels of < 13 g/dL
      during the year of onset and the prior year for cases and during the index year
      and year prior for controls. Logistic regression was used to estimate odds ratios
      (OR). The retrospective cohort study used the 618 residents of Olmsted County,
      MN, who were > or = 65 years of age and whose anemia, as defined above, was newly
      recognized in 1986. Standardized incidence ratios (SIR) for AD were estimated by
      use of the person-years of follow-up in the cohort and the incidence rates of AD
      for this community. RESULTS: In the case-control study, an almost twofold
      increase in occurrence of AD was associated with anemia (OR, 1.88; 95% CI, 1.17
      3.03). For men and women, respectively, the ORs were 1.81 (95% CI, 0.75-4.39) and
      1.96 (95% CI, 1.11-3.47). The cohort study showed no overall increase in risk of
      AD (SIR, 0.98; 95% CI, 0.67-1.37). For men, the SIR was a comparable 1.49 (95%
      CI, 0.79-2.56), whereas for women the SIR was only 0.79 (95% CI, 0.49-1.23).
      CONCLUSIONS: Although anemia may be a risk factor for AD in the elderly, the
      mechanism by which anemia contributes to the pathogenesis of AD or to the
      unmasking of AD symptoms is unknown.

PMID- 9141647
TI  - Appositions made by axons of descending interneurons in the guinea-pig small
      intestine, investigated by confocal microscopy.
AB  - There are four major classes of descending interneurons in the myenteric plexus
      of the guinea-pig small intestine. In this study, the connections made by two of
      these classes of descending interneurons with other interneurons and with
      inhibitory motor neurons have been investigated using confocal, conventional
      fluorescence and electron microscopy. The terminals of descending interneurons
      known to contain both bombesin (BN) and nitric oxide synthase (NOS) were
      identified by BN immunoreactivity (IR). Cholinergic interneurons known to contain
      somatostatin (SOM) were identified by SOM-IR. The connections of these two groups
      of interneurons with the following three classes of nerve cell bodies were
      examined: those with NOS-IR that also contain gamma-aminobutyric acid (GABA)
      (inhibitory motor neurons), those with only NOS-IR (descending interneurons and
      inhibitory motor neurons) and those with only GABA-IR (motor neurons). The BN-IR
      and SOM-IR interneurons were found to form connections with each other, and both
      types of interneurons provided inputs to motor neurons. Most previous analyses of
      interconnections in the enteric plexuses have been by conventional fluorescence
      microscopy and electron microscopy. In the present work these are compared with
      confocal microscopy. BN-IR varicosities formed pericellular baskets around each
      class of nerve cell that were easily identifiable with all techniques. Using
      confocal microscopy, BN-IR varicosities that were in contact with NOS-IR and GABA
      IR nerve cells were quantified. Confocal microscopy demonstrated over twice as
      many contacts as were shown by a previous electron microscopic study. In
      contrast, conventional fluorescence microscopy showed little indication that SOM
      IR varicosities formed inputs to NOS-IR or GABA-IR nerve cells, despite the fact
      that confocal microscopy revealed direct appositions and electron microscopy
      revealed synapses. This study has shown that confocal analysis is a valuable
      adjunct to conventional fluorescence microscopy for determining neuronal
      circuitry. Moreover, it allows a more rapid collection of data than does electron
      microscopy. It is concluded that chains of BN-IR and SOM-IR interneurons from
      descending pathways in the small intestine and that both types of interneuron
      connect with muscle motor neurons.

PMID- 9141648
TI  - Colocalization of parvalbumin and calbindin D-28k in neurons including chandelier
      cells of the human temporal neocortex.
AB  - Chandelier cells are cortical GABAergic interneurons with a unique synaptic
      specificity enabling them to exert a strong inhibitory influence on pyramidal
      cells. By using immunocytochemistry for the calcium-binding protein calbindin D
      28k in the human temporal neocortex, we have found numerous immunoreactive
      processes that were identified as chandelier cell axon terminals. This was a
      striking find since in previous immunocytochemical studies of the primate
      neocortex, chandelier cell axon terminals had been shown to be immunoreactive for
      another calcium-binding protein, parvalbumin, and colocalization studies indicate
      that parvalbumin and calbindin are present in almost completely separate neuronal
      populations. Here, we present double-label immunofluorescence experiments showing
      that parvalbumin and calbindin immunoreactivities are colocalized in certain
      neurons that include a subpopulation of chandelier cells whose cell bodies are
      located mainly in layers V and VI of the human temporal neocortex. The results
      suggest a selective laminar distribution of neurochemical subtypes of chandelier
      cells which is a peculiar feature of the organization of the human neocortex.

PMID- 9141649
TI  - Distribution and pharmacological characterization of somatostatin receptor
      binding sites in the sheep brain.
AB  - Somatostatin binding sites have been localized and quantified in the sheep brain
      using 125I-Tyr0-DTrp8-somatostatin, by quantitative high resolution light
      microscopic autoradiography. Sections were analyzed by densitometry on
      radioautographic film, and subsequently on slides coated with photoemulsion.
      Specific somatostatin binding sites were concentrated in the medial habenula,
      superior colliculus, dorsal motor nucleus of the vagus nerve, inferior olive,
      spinal trigeminal nucleus, and cerebellum. In competition experiments,
      octreotide, a sst2/sst3/sst5 selective agonist only partially displaced 125I-Tyr0
      DTrp8-somatostatin in the three cerebellar layers while it was fully active as
      compared to somatostatin 14 and 28 in the deeper layers of the parietal cortex.
      Moderate to low somatostatin receptor densities were present in the mesencephalic
      periaqueductal gray, dorsal raphe, thalamic paraventricular nucleus,
      interpeduncular nucleus, pineal gland, dorsal tegmental, dorsolateral tegmental
      and parabrachial nuclei, nucleus of the solitary tract. The distribution of
      somatostatin binding sites generally correlates with the data obtained on slides
      dipped in photoemulsion which provided better resolution and more precise
      localization. In most of the labeled areas, 125I-Tyr0-DTrp8-somatostatin receptor
      binding was distributed between both neuropil and perikarya. Perikarya bearing
      125I-Tyr0-DTrp8-somatostatin receptors were observed in areas which did not
      display detectable binding sites on film such as the preoptic-anterior
      hypothalamic complex and arcuate nucleus and in the locus coeruleus. In
      conclusion, the distribution of 125I-Tyr0-DTrp8-somatostatin binding sites in
      sheep brain is very reminiscent of other mammals being closer to the human than
      to rodents.

PMID- 9141650
TI  - Immunocytochemical detection of the neurokinin B receptor (NK3) on melanin
      concentrating hormone (MCH) neurons in rat brain.
AB  - The presence of the neurokinin B receptor (NK3 receptor) in the rat lateral
      hypothalamus and the zona incerta was previously reported. The aim of the present
      study was to define its cellular localization in these areas. Investigations,
      coupling immunocytochemical and in situ hybridization techniques, focussed on two
      neuron populations: the melanin-concentrating hormone (MCH) neurons and a
      population of neurons recognized by an ovine prolactin antiserum (PRL-ir
      neurons). While PRL-ir neurons did not exhibit NK3 immunoreactivity, 57% +/- 6%
      of MCH neurons were strongly stained by the NK3 antiserum. These results suggest
      that neurokinin B is involved in the regulation of MCH neuron activity via the
      NK3 receptor; they provide new bases for further investigations on MCH role in
      the control of food and water intake.

PMID- 9141651
TI  - Distribution of cholecystokinin immunoreactivity in the BALB/c mouse forebrain:
      an immunocytochemical study.
AB  - The present study describes cholecystokinin (CCK) immunoreactivity (CCK-IR)
      distribution in the brains of control and colchicine-treated mice. In the brains
      of control mice, the CCK-IR strongly revealed numerous axons and terminals.
      Perikarya exhibiting a faint to moderate immunoreactivity were also observed in
      areas such as cortices, hippocampus, amygdala, septum, and thalamus. The
      colchicine treatment did not seem to notably affect the brain CCK-IR innervation,
      but resulted in profound changes of the perikaryal staining. Indeed, the regions,
      which contained numerous moderately stained perikarya in the control animals,
      exhibited after colchicine treatment immunoreactive perikarya intensely stained
      but only in moderate number. This feature obviously appeared in the cortex in
      which, in addition to strongly stained perikarya, colchicine induced the
      appearance of numerous CCK-IR hillocks. In the lateral amygdala and thalamus of
      colchicine-treated animals, the somatic immunoreactivity was considerably
      decreased. The regions, such as paraventricular hypothalamic nucleus and bed
      nucleus of the stria terminalis, which in the control animals did not exhibit any
      stained perikaryon, showed a high number of strongly stained cell bodies after
      colchicine treatment. This study, mapping the mouse forebrain CCK-IR,
      demonstrated a wide distribution of this peptide. Moreover, CCK-IR is
      spontaneously visible in neurons of untreated mouse in some brain areas
      previously shown in the rat to exhibit CCK mRNA, but no clear perikaryal CCK-IR
      even after colchicine treatment.

PMID- 9141652
TI  - Peptide localization in the mouse inferior olive.
AB  - The inferior olivary complex is the sole source of climbing fibers to the
      cerebellar cortex. Physiologically these afferents have been shown to have a
      powerful excitatory effect on their target neurons, namely Purkinje cells. Thus,
      any modulation of olivary firing rate or responsiveness will alter Purkinje cell
      firing and ultimately cerebellar function. Neuropeptides have been shown to
      modulate neuronal activity in several systems. The intent of the present study is
      to determine the olivary distribution of five peptides previously shown to be
      present and functional in cerebellar circuitry including cholecystokinin,
      calcitonin gene-related peptide, corticotropin releasing factor, enkephalin and
      substance P. These studies were carried out in the adult C57BL/6J mouse using the
      peroxidase anti-peroxidase immunohistochemical technique. All five peptides
      labeled varicosities of varying sizes. Varicosities labeled for cholecystokinin,
      calcitonin gene-related peptide and corticotropin releasing factor were densely
      distributed throughout the inferior olive. In contrast, varicosities
      immunostained for substance P and enkephalin, were more restricted in their
      distribution. The overlap in the distribution of these peptides suggests that
      they may be colocalized with each other as well as with excitatory or inhibitory
      amino acids known to be present in afferents to the inferior olive. Because of
      the extensive distribution of the peptides, it is likely that they are derived
      from multiple brainstem sources. These findings serve as baseline data for future
      physiological studies designed to address the functional role of peptides in
      olivary circuitry.

PMID- 9141653
TI  - Perspectives on research support: toward a more signal-averaged view.

PMID- 9141654
TI  - Koeppen named physiology teacher of the year.

PMID- 9141655
TI  - Molecular mechanisms of azole resistance in fungi.
AB  - This paper reviews the current status of our understanding of azole antifungal
      resistance mechanisms at the molecular level and explores their implications.
      Extensive biochemical studies have highlighted a significant diversity in
      mechanisms conferring resistance to azoles, which include alterations in sterol
      biosynthesis, target site, uptake and efflux. In stark contrast, few examples
      document the molecular basis of azole resistance. Those that do refer almost
      exclusively to mechanisms in laboratory mutants, with the exception of the role
      of multi-drug resistance proteins in clinical isolates of Candida albicans. It is
      clear that the technologies required to examine and define azole resistance
      mechanisms at the molecular level exist, but research appears distinctly lacking
      in this most important area.

PMID- 9141656
TI  - In vivo production of A-protein, lipopolysaccharide, iron-regulated outer
      membrane proteins and 70-kDa serine protease by Aeromonas salmonicida subsp.
      salmonicida.
AB  - Using specific immunostaining of Western blots, the in vivo expression of several
      putative virulence factors of Aeromonas salmonicida subsp. salmonicida was
      demonstrated in infected muscle tissue of Atlantic salmon and rainbow trout.
      Three virulent isolates of A. salmonicida were used. One isolate was chosen
      because in vitro it was apparently a non-producer of the 70-kDa serine protease.
      Infected furuncle tissue was centrifuged and samples of the pellet and
      supernatant probed for evidence that the components of interest were bacterial
      cell-associated or secreted. The A-protein was detected in pelleted furuncle
      material but not in the supernatant. Lipopolysaccharide, both high and low
      molecular mass, was present in the pellet but only high molecular mass
      lipopolysaccharide was detected in the furuncle supernatant. Iron-regulated outer
      membrane proteins were detected in the furuncle pellet. The 70-kDa serine
      protease was detected in the furuncle supernatant of both protease-producing
      strains. However, whilst the protease-deficient isolate was demonstrated to
      produce low levels of the 70-kDa protease when grown in vitro under iron
      restricted conditions, none could be detected in vivo.

PMID- 9141657
TI  - Cloning and transcriptional analysis of the lipA (lipoic acid synthetase) gene
      from Rhizobium etli.
AB  - We report here the isolation of a Rhizobium etli gene involved in lipoic acid
      metabolism, the lipA gene, which complements a lipA mutant strain of Escherichia
      coli. A promoter region (lipAp) was mapped immediately upstream of lipA and two
      in vivo transcription initiation sites were identified, preceded by sequences
      showing some homology to the -10/-35 promoter consensus sequences. The activity
      of the lipAp was found not to be regulated either by the carbon source or by the
      addition of lipoic acid. Moreover, quantitative analysis of the lipA transcript
      by RNase protection assays indicated its down-regulation during entry into
      stationary phase.

PMID- 9141658
TI  - Induction of flagellation and a novel agar-penetrating flagellar structure in
      Salmonella enterica grown on solid media: possible consequences for serological
      identification.
AB  - Salmonella enterica grown on solid medium containing iron, thiosulfate and 100 mM
      hexoses and amino acids underwent cell surface differentiation involving
      increased flagellation (electrophoretic isotypes 60, 54 and 50 kDa), conversion
      from rough to smooth lipopolysaccharide, and assembly of a matrix that penetrated
      1.4% agar. Flagellation was also induced in the avian pathogen S. enterica var
      Pullorum, which is diagnostically defined as aflagellate. Induction correlated
      closely with a simple colonial color change when Hektoen Enteric agar was used as
      the basal growth medium. Group D1 egg-contaminating Salmonella grown under
      inducing conditions deviated from their expected H-antigen immunoreactivity,
      suggesting possible consequences for the interpretation of the Kauffman-White
      identification scheme.

PMID- 9141659
TI  - Characterization of two Streptomyces ambofaciens recA mutants: identification of
      the RecA protein by immunoblotting.
AB  - The recA gene was isolated from Streptomyces ambofaciens DSM40697. Its nucleotide
      sequence predicted a protein of 372 residues. Two recA mutants, NSAR1001 and
      NSAR57, obtained by gene disruption encoded a RecA protein lacking respectively
      30 and at least 62 amino acids from the C-terminal end. NSAR1001 showed a wild
      type sensitivity to UV light and oxolinic acid. In contrast, NSAR57 was highly
      sensitive to these agents and the loss of the inserted DNA restored the wild-type
      phenotype. Western blot analysis using antiserum to Escherichia coli RecA showed
      that overproduction of RecA was correlated with overtranscription of recA in an
      S. ambofaciens amplified mutant derived from genetic instability.

PMID- 9141660
TI  - Use of an automatic DNA sequencer for S1 mapping: transcriptional analysis of the
      Streptomyces coelicolor A3(2) dnaK operon.
AB  - The transcription start point of the dnaK operon of Streptomyces coelicolor A3(2)
      has been determined by S1 mapping, using the EMBL automated fluorescent DNA
      sequencer. The -35 and -10 hexamers correspond to a sigma 70-type promoter. This
      promoter responds to heat shock and involves an inverted repeat different from
      the CIRCE sequence characteristic of the Gram-positive heat-shock promoters.

PMID- 9141661
TI  - Cloning and molecular analysis of the Aspergillus terreus arg1 gene coding for an
      ornithine carbamoyltransferase.
AB  - An Aspergillus terreus gene (arg1) encoding ornithine carbamoyltransferase
      (OCTase) has been cloned and sequenced. The deduced amino acid sequence contains
      a signal peptide suggestive of a mitochondrial location for the A. terreus
      enzyme. Alignment of the A. terreus OCTase sequence with other OCTases revealed
      the presence of conserved regions. Northern analysis indicates that arg1
      expression is regulated at the level of transcription and that transcription of
      the arg1 gene is not markedly affected by arginine sufficiency. However,
      histidine starvation effected by 3-amino-1,2,4-triazole increased transcription
      of the arg1 gene, indicating cross-pathway regulation of OCTase synthesis in A.
      terreus.

PMID- 9141662
TI  - Dockerin-like sequences in cellulases and xylanases from the rumen cellulolytic
      bacterium Ruminococcus flavefaciens.
AB  - Recent analysis of the endA cellulase gene from Ruminococcus flavefaciens 17 has
      revealed that it encodes a product of 759 amino acids that provides the first
      example of a multidomain cellulase from a Ruminococcus sp. Following the family 5
      catalytic domain in the predicted EndA enzyme is a 282 amino acid domain of
      unknown function for which no close relationship was found to other protein
      sequences. However, the C-terminal sequences of EndA contain a 34 amino acid
      threonine-rich linker connected to an 81 amino acid region, both of which show
      strong similarities to sequences present in two xylanases from R. flavefaciens
      17. A distant relationship is evident between regions of the 80 amino acid
      sequences of EndA, XynD and XynB and the duplicated 23 amino acid dockerin
      sequences found in cellulolytic Clostridium sp., suggesting that as in
      Clostridium sp. these sequences could mediate the binding of enzymatic
      polypeptides to another component in the cell surface enzyme complex of R.
      flavefaciens.

PMID- 9141663
TI  - Regulation of cyclodextrin glucanotransferase synthesis in Bacillus ohbensis.
AB  - The production of cyclodextrin glucanotransferase (CGTase) by Bacillus ohbensis
      is dependent on the presence of starch and inhibited by glucose in the medium.
      Northern blot analysis revealed that the CGTase gene (cgt) was transcribed to
      almost the same level irrespective of the presence or absence of starch, but
      glucose completely repressed the transcription. Furthermore, a relatively high
      amount of CGTase protein was detected on Western blotting only in the medium with
      starch, showing the lack of posttranslational control of the CGTase activity.
      These findings suggest some starch induction mechanism for the cgt gene, possibly
      at the posttranscriptional level, besides negative transcriptional regulation by
      glucose.

PMID- 9141664
TI  - Structural characterization of lipid A obtained from Pantoea agglomerans
      lipopolysaccharide.
AB  - Lipopolysaccharide isolated from Pantoea agglomerans showed higher priming and
      triggering activities for macrophages in terms of tumor necrosis factor
      production than other lipopolysaccharides. To identify the difference in
      biological activities of lipopolysaccharide of Pantoea agglomerans from other
      lipopolysaccharides on the basis of structure, we determined the structure of the
      lipid A part, which is the biological center of lipopolysaccharides, by
      quantitative analysis, nuclear magnetic resonance spectroscopy and mass
      spectrometry. Lipopolysaccharide of Pantoea agglomerans is constructed with at
      least two kinds of lipid A of different levels of acylation. One is of the same
      type as that of Escherichia coli with hexa-acyl lipid A and the other is the
      Salmonella minnesota type with hepta-acyl lipid A.

PMID- 9141665
TI  - Bacillus cereus may produce two or more diarrheal enterotoxins.
AB  - Bacillus cereus strains were tested for production of diarrheal enterotoxin by
      the reverse passive latex agglutination test and for presence of B. cereus
      enterotoxin gene (bceT) by polymerase chain reaction. About 50% of 56 B. cereus
      strains reacted positive in broth culture in the reverse passive latex
      agglutination test, while the bceT gene was detected in 41.1%. Sixteen percent of
      the strains were positive for both diarrheal enterotoxin and bceT gene. A 741 bp
      probe prepared from the polymerase chain reaction product detected bceT gene in
      all strains that were positive with the polymerase chain reaction. This study
      indicates a likelihood of two or more enterotoxins being produced by B. cereus
      which may be involved in causing diarrheal type food poisoning.

PMID- 9141666
TI  - Effect of leader peptide mutations on biosynthesis of the lantibiotic Pep5.
AB  - Lantibiotics are lanthionine-containing antibiotic peptides which are synthesized
      from ribosomal prepeptides by post-translational modification. In order to
      elucidate the function of a conserved motif in the N-terminal leader sequence of
      lantibiotic prepeptides, three amino acids were exchanged in the leader peptide
      sequence of the lantibiotic Pep5. Exchanging Phe-19 for Ser and Glu-16 for Lys in
      the FDLEI-motif, reduced Pep5 production to 35 and 38% of the control whereas,
      after exchanging Asp-6 for Ser and Glu-16 for Lys in the FDLEI-motif, reduced
      Pep5 production to 35 and 38% of the control whereas, after exchanging ASp-6 for
      Lys, the production was decreased only to 82%. Proteolytic fragments of Pep5 or
      incorrectly modified Pep5 molecules, indicative of incorrect modifications, were
      not found in the culture supernatant. Thus, in contrast to the biosynthesis of
      the lantibiotic nisin, the FDLEI-motif is not essential for biosynthesis of Pep5
      and has no influence on correct ring formation or processing, but seems to be
      important for optimal biosynthesis rates.

PMID- 9141667
TI  - Characterization of IS1474, an insertion sequence of the IS21 family isolated
      from Pseudomonas alcaligenes NCIB 9867.
AB  - A new insertion sequence (IS) designated IS1474 was isolated from Pseudomonas
      alcaligenes NCIB 9867 (P25X). IS1474 is a 2632 bp element which showed a
      characteristic IS structure with 12 bp inverted repeats (IRs) flanking a 2608 bp
      central region. IS1474 contained four open reading frames (ORF1-ORF4), two in
      each orientation. Similarities were detected between ORF1 and ORF2 and the
      putative transposases of the IS21 family. Sequences upstream from IS1474 were
      found to display up to 89% homology with IS53 from Pseudomonas syringae
      suggesting that IS1474 had inserted into another related IS element designated
      IS1475. An open reading frame, ORF5, located at the junction of IS1474 and
      IS1475, showed similarities with the IstB protein of IS21 and could possibly be
      the transposase subunit of IS1475. Transposition assays showed that IS1474
      transposed at a relatively low frequency leading to cointegration with target
      plasmids. Hybridization studies showed that IS1474 is present in at least 13
      copies in the chromosome of P25X and one copy on its endogenous plasmid.

PMID- 9141668
TI  - Properties of C-terminal truncated derivatives of the activator, StrR, of the
      streptomycin biosynthesis in Streptomyces griseus.
AB  - The StrR protein is a DNA-binding protein activating the transcription of
      streptomycin biosynthesis of Streptomyces griseus N2-3-11 and Streptomyces
      glaucescens. A putative helix-turn-helix motif located between amino acid
      positions 207 and 227 of the StrR protein was identified as a prerequisite for
      its DNA-binding properties. Although, C-terminal truncated StrR proteins were
      able to interact with StrR-binding sites, they failed to activate transcription
      from the StrR-dependent promotor strB1p. Therefore, the C-terminal domain of StrR
      seemed to be necessary for its function as transcriptional activator.

PMID- 9141669
TI  - On the catalase-peroxidase gene, katG, of Mycobacterium leprae and the
      implications for treatment of leprosy with isoniazid.
AB  - The toxicity of the potent tuberculocidal agent, isoniazid, is mediated by the
      heme-containing enzyme, catalase-peroxidase, encoded by the katG gene. Although
      isoniazid has been used for the treatment of leprosy, it is shown here that the
      katG gene of Mycobacterium leprae is a pseudogene, which has probably been
      inactivated by multiple mutations. Inactive genes were detected by the polymerase
      chain reaction in several isolates of M. leprae, of different geographical
      origins, and attempts to complement an isoniazid-resistant strain of
      Mycobacterium smegmatis with the katG pseudogene were unsuccessful. Isoniazid is
      thus likely to be of no therapeutic benefit to leprosy patients.

PMID- 9141670
TI  - Properties of yeast expressed Aspergillus nidulans chitin synthase B which is
      essential for hyphal growth.
AB  - A complementary DNA of the Aspergillus nidulans chsB gene encoding chitin
      synthase, an essential gene for hyphal growth, was obtained by RT-PCR and
      expressed in Saccharomyces cerevisiae by using the GAL1 promoter in a multicopy
      plasmid. The biochemical characteristics of chitin synthase B (ChsB) expressed in
      S. cerevisiae were examined. The chitin synthase B produced in galactose medium
      showed zymogenicity due to activation by trypsin treatment and required Mg2+ ion
      to exert maximal activity. It was competitively inhibited by polyoxin D. The Ki
      value of the inhibitor was 10 microM, and the K(m) for the substrate was 1.6 mM.
      The activity was enhanced by the addition of N-acetylglucosamine. The optimal pH
      is 7.5 when Mg2+ is used. These characteristics are the same as those of other
      chitin synthases.

PMID- 9141671
TI  - S-layers of Bacillus species.

PMID- 9141672
TI  - Membrane topology analysis of the Bacillus subtilis BofA protein involved in pro
      sigma K processing.
AB  - The Bacillus subtilis BofA protein is involved in regulation of pro-sigma K
      processing in the mother cell during the late stages of sporulation. A computer
      analysis of the BofA amino acid sequence indicates that it is an integral
      membrane protein. To determine the membrane topology of the protein, a series of
      gene fusions of bofA with lacZ or phoA reporter genes in Escherichia coli were
      analysed. A BofA topological model with two membrane-spanning segments, and with
      the N- and the C-terminal domains located in the region between the inner and
      outer membranes surrounding the forespore is presented. The analysis of different
      modifications of the last five amino acid residues of the BofA protein, obtained
      by PCR site-directed mutagenesis, suggests a possible role of the C-terminal
      domain in the regulation of pro-sigma K processing.

PMID- 9141673
TI  - Expression analysis of the ssgA gene product, associated with sporulation and
      cell division in Streptomyces griseus.
AB  - The ssgA gene of Streptomyces griseus B2682, when present in high copy number,
      results in both suppression of sporulation and fragmented growth of mycelia.
      Western analysis with polyclonal antibodies against the gene product (SsgA)
      revealed a close correlation between SsgA accumulation and the onset of
      sporulation in wild-type cells. The protein was only detected in the cytoplasm.
      Certain developmental mutants of S. griseus (afs, reIC and brgA) which are
      defective in aerial mycelium formation in solid culture and submerged spore
      formation in liquid culture failed to accumulate SsgA. The SsgA protein appeared
      shortly (1 h) after nutritional shift-down of strain B2682 cells. afs mutant
      cells sporulated and expressed SsgA only when A-factor was present both before
      and after nutritional shift-down. Introduction of the ssgA gene in a low-copy
      number vector into strain B2682 resulted in fivefold overexpression of SsgA, and
      was accompanied by fragmented growth of mycelia and suppression of submerged
      spore formation (in liquid culture) and aerial mycelium formation (in solid
      culture). Streptomycin production was not inhibited. In a control experiment, a
      nonfunctional ssgA gene possessing a frameshift mutation near its N-terminus had
      no effect on either growth or sporulation. It is proposed that the ssgA gene
      product plays a role in promoting the developmental process of S. griseus.

PMID- 9141674
TI  - Periplasmic cyclic 1,2-beta-glucan in Brucella spp. is not osmoregulated.
AB  - Biosynthesis of periplasmic cyclic 1,2-beta-glucans in Brucella ovis strain
      REO198 and B. abortus strain 519 was found to be carried out by membrane-bound
      enzymes that use UDP-glucose (UDP-Glc) as donor substrate. Contrary to what
      happens in species of the genera Agrobacterium and Rhizobium, the accumulation of
      the reaction products in Brucella appeared not to be osmotically regulated.
      Incubation of permeabilized cells with UDP-[14C]Glc led to the formation of
      soluble neutral cyclic 1,2-beta-glucans and [14C]glucose-labelled glucoproteins.
      PAGE of pulse-chase experiments carried out with permeabilized cells showed that
      the molecular mass of the labelled protein was indistinguishable from
      Agrobacterium tumefaciens A348 and Rhizobium fredii USDA191 glucoproteins known
      to be intermediates in the synthesis of cyclic glucans. Brucella total membrane
      preparations were less efficient than permeabilized cells in the formation of
      cyclic glucan; this was attributed to defective cyclization. Accumulation of
      protein intermediates having oligosaccharides of high molecular mass that were
      not released from the protein was observed after chase with 2 mM UDP-Glc. This
      defect was not observed when permeabilized cells were used as enzyme preparation,
      thus suggesting that in Brucella a factor(s) that was lost or inactivated upon
      the preparation of membranes was required for the effective regulation between
      elongation and cyclization reactions.

PMID- 9141675
TI  - Comparative physiology of salt tolerance in Candida tropicalis and Saccharomyces
      cerevisiae.
AB  - The salt tolerance of the respiratory yeast Candida tropicalis and the
      fermentative yeast Saccharomyces cerevisiae have been compared in glucose media.
      C. tropicalis showed a better adaptation to Na+ and Li+ and maintained higher
      intracellular K+:Na+ and K+:Li+ ratios than S. cerevisiae. However, C. tropicalis
      showed a poorer adaptation to osmotic stress (produced by KCl and sorbitol) and
      exhibited reduced glycerol production as compared to S. cerevisiae. In media with
      the non-repressing sugar galactose as carbon source, S. cerevisiae exhibited
      reduced glycerol production and increased sensitivity to osmotic stress. Under
      these conditions, S. cerevisiae, but not C. tropicalis, utilized trehalose as a
      more important osmolyte than glycerol. These results suggest that the relative
      tolerance of yeast to the osmotic and cation toxicities of NaCl, and the
      underlying relative capabilities for osmolyte synthesis and cation transport, are
      modulated by the general catabolite control exerted by glucose.

PMID- 9141676
TI  - Metabolic flux response to salt-induced stress in the halotolerant yeast
      Debaryomyces hansenii.
AB  - The toxic effect of NaCl and KCl on growth of the marine yeast Debaryomyces
      hansenii on glucose or glycerol was studied. Above a threshold value, both salts
      reduced the specific growth rate, specific glucose and glycerol respiration rates
      and specific glucose fermentation rate, as well as biomass yields. The
      exponential inhibition constant, k, and minimum toxic concentration, Cmin were
      similar for all physiological parameters assayed. The effect of either salt on
      the specific activity of several glycolytic enzymes showed a similar inhibition
      pattern, although at much lower salt concentrations compared with the
      physiological parameters. In agreement with published results on glycerol
      phosphate dehydrogenase stimulation by salt, we present evidence that a general
      glycolytic flux deviation could occur naturally during salt stress, due to the
      intrinsic sensitivity of the glycolytic enzymes to intracellular ion
      concentrations.

PMID- 9141677
TI  - Characterization of genes for the biosynthesis of the compatible solute ectoine
      from Marinococcus halophilus and osmoregulated expression in Escherichia coli.
AB  - The genes of the biosynthetic pathway of ectoine (1,4,5,6-tetrahydro-2-methyl-4
      pyrimidinecarboxylic acid) from the Gram-positive moderate halophile Marinococcus
      halophilus were cloned by functional expression in Escherichia coli. These genes
      were not only expressed, but also osmoregulated in E. coli, as demonstrated by
      increasing cytoplasmic ectoine concentration in response to medium salinity.
      Sequencing of a 4.4 kb fragment revealed four major ORFs, which were designated
      ectA, ectB, ectC and orfA. The significance of three of these genes for ectoine
      synthesis was proved by sequence comparison with known proteins and by
      physiological experiments. Several deletion derivatives of the sequenced fragment
      were introduced into E. coli and the resulting clones were investigated for their
      ability to synthesize ectoine or one of the intermediates in its biosynthetic
      pathway. It was demonstrated that ectA codes for L-2,4-diaminobutyric acid
      acetyltransferase, ectB for L-2,4-diaminobutyric acid transaminase and ectC for L
      ectoine synthase. A DNA region upstream of ectA was shown to be necessary for the
      regulated expression of ectoine synthesis in response to the osmolarity of the
      medium.

PMID- 9141678
TI  - Purification of two Bacillus subtilis proteins which cross-react with antibodies
      directed against eukaryotic protein kinase C, the His HPr kinase and trigger
      factor.
AB  - As in eukaryotes, phosphorylation of Ser residues in proteins appears to be
      common phenomenon in bacteria. Surprisingly, however, very few Ser/Thr protein
      kinases have been identified and in this study antibodies directed against
      mammalian protein kinase C (PKC) have been used in attempts to isolate conserved
      Ser/Thr protein kinases. Using the mAb M7 against rat brain PKC, a single 70 kDa
      band was identified in total cell extracts of Bacillus subtilis by Western
      blotting after SDS-PAGE, whilst using polyclonal antibody alpha-PKC1p against
      Saccharomyces cerevisiae PKC a single 67 kDa band was identified by the same
      procedure. The two proteins were purified independently on the basis of antibody
      recognition employing two-dimensional gel electrophoresis as a final step, which
      allowed subsequent microsequencing. The 70 kDa band was thus identified as the
      phosphoenolpyruvate-dependent His HPr kinase, Enzyme 1 of the phosphotransferase
      system. This identity was confirmed using a mutant deleted for ptsl, encoding
      Enzyme 1. The 67 kDa protein was identified as a previously unknown B. subtilis
      'trigger factor', homologous to an Escherichia coli protein-folding enzyme,
      peptidylprolyl cis-trans-isomerase implicated in cell division.

PMID- 9141679
TI  - Isolation and characterization of the gene encoding single-stranded-DNA-binding
      protein (SSB) from four marine Shewanella strains that differ in their
      temperature and pressure optima for growth.
AB  - The ssb gene, coding for single-stranded-DNA-binding protein (SSB), was cloned
      from four marine Shewanella strains that differed in their temperature and
      pressure optima and ranges of growth. All four Shewanella ssb genes complemented
      Escherichia coli ssb point and deletion mutants, with efficiencies that varied
      with temperature and ssb gene source. The Shewanella SSBs are the largest
      bacterial SSBs identified to date (24.9-26.3 kDa) and may be divided into
      conserved amino- and carboy-terminal regions and a highly variable central
      region. Greater amino acid sequence homology was observed between the Shewanella
      SSBs as a group (72-87%) than with other bacterial SSBs (52-69%). Analysis of the
      amino acid composition of the Shewanella SSBs revealed several features that
      could correlate with pressure or temperature adaptation. SSBs from the three low
      temperature-adapted Shewanella strains were an order of magnitude more
      hydrophilic than that from the mesophilic strain, and differences in the
      distribution of eight amino acids were identified which could contribute to
      either the temperature or pressure adaptation of the proteins. The SSBs from all
      four Shewanella strains were overproduced and partially purified based upon their
      ability to bind single-stranded DNA. The differences found among the Shewanella
      SSBs suggest that these proteins will provide a useful system for exploring the
      adaptation of protein-protein and protein-DNA interactions at low temperature and
      high pressure.

PMID- 9141680
TI  - The ability of Escherichia coli O157:H7 to decrease its intracellular pH and
      resist the toxicity of acetic acid.
AB  - Batch cultures of Escherichia coli K-12 grew well in an anaerobic glucose medium
      at pH 5.9, but even small amounts of acetate (20 mM) inhibited growth and
      fermentation. E. coli O157:H7 was at least fourfold more resistant to acetate
      than K-12. Continuous cultures of E. coli K-12 (pH 5.9, dilution rate 0.085 h-1)
      did not wash out until the sodium acetate concentration in the input medium was
      80 mM, whereas E. coli O157:H7 persisted until the sodium acetate concentration
      was 160 mM. E. coli K-12 cell accumulated as much as 500 mM acetate, but the
      intracellular acetate concentration of O157:H7 was never greater than 300 mM.
      Differences in acetate accumulation could be explained by intracellular pH and
      the transmembrane pH gradient (delta pH). E. coli K-12 maintained a more or less
      constant delta pH (intracellular pH 6.8), but E. coli O157:H7 let its delta pH
      decrease from 0.9 to 0.2 units as sodium acetate was added to the medium. Sodium
      acetate increased the rate of glucose consumption, but there was little evidence
      to support the idea that acetate was creating a futile cycle of protons.
      Increases in glucose consumption rate could be explained by increases in D
      lactate production and decreases in ATP production. Intracellular acetate was
      initially lower than the amount predicted by delta pH, but intracellular acetate
      and delta pH were in equilibrium when the external acetate concentrations were
      high. Based on these results, the acetate tolerance of O157:H7 can be explained
      by fundamental differences in metabolism and intracellular pH regulation. By
      decreasing the intracellular pH and producing large amounts of D-lactate, O157:H7
      is able to decrease delta pH and prevent toxic accumulations of intracellular
      acetate anion.

PMID- 9141681
TI  - Tellurite reductase activity of nitrate reductase is responsible for the basal
      resistance of Escherichia coli to tellurite.
AB  - Tellurite and selenate reductase activities were identified in extracts of
      Escherichia coli. These activities were detected on non-denaturing polyacrylamide
      gels using an in situ methyl viologen activity-staining technique. The activity
      bands produced from membrane-protein extracts had the same RF values as those of
      nitrate reductases (NRs) A and Z. Tellurite and selenate reductase activities
      were absent from membranes obtained from mutants deleted in NRs A and Z. Further
      evidence of the tellurite and selenate reductase activities of NR was
      demonstrated using rocket immunoelectrophoresis analysis, where the tellurite and
      selenate reductase activities corresponded to the precipitation arc of NR.
      Additionally, hypersensitivity to potassium tellurite was observed under aerobic
      growth conditions in nar mutants. The tac promoter expression of NR A resulted in
      elevated tellurite resistance. The data obtained also imply that a minimal
      threshold level of NR A is required to increase resistance. Under anaerobic
      growth conditions additional tellurite reductase activity was identified in the
      soluble fraction on non-denaturing gels. Nitrate reductase mutants were not
      hypersensitive under anaerobic conditions, possibly due to the presence of this
      additional reductase activity.

PMID- 9141682
TI  - Copper-inducible transcriptional regulation at two promoters in the Escherichia
      coli copper resistance determinant pco.
AB  - The pco determinant of Escherichia coli plasmid pRI1004 encodes inducible
      resistance to the trace element copper. The identification of two copper
      dependent transcriptional initiation regions within pco that each contain a
      similar upstream hyphenated dyad motif is described. Deletion constructs showed
      that this 'copper box' motif was essential for copper-inducible activity at both
      pco promoters, PpcoA and PpcoE. The placement of the motif differs in the two
      promoters, and PpcoA contains an extended -10 nonamer typical of promoters for
      which RNA polymerase does not bind specifically to -35 sequences. PpcoE does not
      contain this motif and is the more strongly expressed promoter. The transcript
      from PpcoA contains the pcoABCDRS genes, while PpcoE expresses only pcoE. The
      induction profiles for PpcoA- and PpcoE-IacZ fusions were flattened sigmoidal
      curves with a gradual response to increasing copper concentration. On high-copy
      number plasmids, zinc was found also to induce transcription from both promoters
      in vivo. Both promoters showed inducible activity in the absence of pcoRS, the
      plasmid-borne two-component regulatory system, indicating that a second trans
      acting regulatory system is present on the chromosome. The pcoR product showed
      repressor action in the absence of pcoS, while still allowing induction,
      suggesting the chromosome encoded a similar two-component system to pco. TnphoA
      insertion mutagenesis identified chromosomal genes which affected promoter
      expression, including ptsH, ptsI (sugar phosphotransferase system) and cya
      (adenylate cyclase). The results support that idea that pco-encoded copper
      resistance is an auxiliary mechanism for handling copper, the regulation of which
      is integrated with the chromosomal regulation of cellular copper metabolism.

PMID- 9141683
TI  - Expression of a Butyrivibrio fibrisolvens E14 gene (cinB) encoding an enzyme with
      cinnamoyl ester hydrolase activity is negatively regulated by the product of an
      adjacent gene (cinR).
AB  - A second cinnamoyl ester hydrolase (CEH) encoding gene (cinB) has been
      characterized from the ruminal bacterium Butyrivibrio fibrisolvens E14. CinB is
      more similar to CinA (previously named CinI) (28% amino acid identify), the first
      CEH described from B. fibrisolvens E14, than either of the enzymes are to any
      other member of the family of hydrolases to which they belong. Upstream of cinB,
      and in the opposite orientation, is a gene (cinR) encoding a protein with
      substantial similarity to members of the MarR family of negative regulators of
      bacterial gene expression. By alignment of these sequences, a possible helix-turn
      helix DNA-binding domain has been identified. CinR was expressed at a high level
      in Escherichia coli using the lac promoter. In E. coli CinR repressed the
      expression of CinB, but had no effect on the expression of CinA. In gel mobility
      shift assays, CinR bound specifically to the cinR-cinB intergenic region. Two
      identical 16 nucleotide inverted repeats adjacent to the putative PcinR and PcinB
      promoters are likely binding sites for CinR. The addition of FAXX (O-[5-O-(trans
      feruloyl)-alpha-L-arabinofuranosyl]-(1,3)- O-beta-D-xylopyranosyl-(1,4)-D
      xylopyranose) and Fara [5-O-(trans-feruloyl)-arabinofuranose], but not xylobiose,
      ferulic acid and a number of other soluble components of hemicellulose, inhibited
      the binding of CinR to DNA.

PMID- 9141684
TI  - Characterization and overexpression of the Aspergillus niger gene encoding the
      cAMP-dependent protein kinase catalytic subunit.
AB  - The gene pkaC encoding the catalytic subunit of cAMP-dependent protein kinase has
      been isolated from the industrially important filamentous fungus Aspergillus
      niger. A probe for screening A. niger phage libraries was generated by a
      polymerase chain reaction using degenerate primers. cDNA and genomic DNA clones
      were isolated and sequenced. An open reading frame of 1440 bp, interrupted by
      three short introns, encodes a polypeptide of 480 amino acids with a calculated
      molecular mass of 53813 Da. The cAMP-dependent protein kinase catalytic subunit
      (PKA-C) from A. niger has a 126 amino acid extension at the N-terminus compared
      to the PKA-C of higher eukaryotes that-except for the first 15 amino acids, which
      are homologous to the Magnaporthe grisea PKA-C-shows no significant similarity to
      the N-terminal extension of PKA-C of other lower eukaryotes. The catalytic core
      of PKA-C of A. niger shows extensive homology with the PKA-C isolated from all
      other eukaryotes. Low-stringency hybridization did not reveal any other pkaC
      homologue in A. niger. The cloned pkaC was used for transformation of A. niger,
      leading to increased levels of pkaC mRNA and PKA-C activity. Transformants
      overexpressing pkaC were phenotypically different with respect to growth, showing
      a more compact colony morphology, accompanied by a more dense sporulation,
      especially on media containing trehalose and glycerol. A number of transformants
      also showed a strongly reduced or complete absence of sporulation. This phenotype
      was quickly lost upon propagation of the strains.

PMID- 9141685
TI  - A carboxy-terminal processing protease gene is located immediately upstream of
      the invasion-associated locus from Bartonella bacilliformis.
AB  - A gene with homology to those encoding an unusual class of C-terminal processing
      proteases that flanks the invasion-associated locus ialAB of Bartonella
      bacilliformis has been identified. The 1302 bp gene, termed ctpA, is located
      immediately upstream of the ialA gene and encodes a predicted nascent product of
      434 amino acids, producing a mature protein of 411 amino acid residues. The
      Bartonella CtpA appears to undergo autolysis in vitro, producing multiple
      products of 43-46 kDa, and a second group of products of 36-37 kDa. Production of
      CtpA in vivo gives a single product of 41.8 kDa. In addition to a computer
      predicted N-terminal secretory signal sequence, the molecular mass difference in
      vivo versus in vitro indicates that CtpA is likely to be secreted and post
      translationally modified. The full-length CtpA protein shows 30% identify to the
      CtpA protein of Synechocystis sp. 6803 (69% overall sequence similarity). The
      mature CtpA protein also has significant homology to the tail-specific protease
      (Tsp) of Escherichia coli, with 22% identify and 62% similarity to an internal
      region of the 660 amino acid Tsp. The CtpA protein does not appear to exhibit
      haemolysin, collagenase, or caseinase activity. The ctpA gene is conserved in all
      Bartonella species examined, as determined by hybridization analyses, but it was
      not found in Brucella abortus or E. coli. The ctpA gene does not directly affect
      the erythrocyte-invasion phenotype conferred by ialAB, but its homology to other
      stress-response processing proteases implies an important role in survival of
      this intracellular pathogen.

PMID- 9141686
TI  - Squalene-hopene cyclase from Bradyrhizobium japonicum: cloning, expression,
      sequence analysis and comparison to other triterpenoid cyclases.
AB  - With the help of a PCR-based screening method, the gene encoding squalenehopene
      cyclase (SHC) of Bradyrhizobium japonicum USDA 110 was isolated from a cosmid
      library. The SHC catalyses the cyclization of squalene to hopanoids, a class of
      triterpenoid lipids recently discovered in nitrogen-fixing, root-nodule-forming
      Bradyrhizobium bacteria. Hybridization experiments showed that the gene is
      present in bacteria of all Bradyrhizobium strains tested and in photosynthetic
      bacteria forming stem nodules on tropical legumes of the genus Aeschynomene. The
      Bradyrhizobium shc gene is 1983 bp in length and encodes a protein of 660 amino
      acid residues with a calculated molecular mass of 73671 Da. Comparison of the
      deduced amino acid sequence with the sequences of other SHCs revealed highest
      similarity (70%) to the SHC from the Gram-negative Zymomonas mobilis and lower
      similarity (48%) to the SHCs from the Gram-positive Alicyclobacillus
      acidocaldarius and Alicyclobacillus acidoterrestris. Bradyrhizobium SHC also
      showed similarity (38-43%) to eukaryotic oxidosqualene cyclases. The B. japonicum
      shc gene was expressed in Escherichia coli. The recombinant SHC catalysed the
      cyclization of squalene to the hopanoids hopene and diplopterol in vitro.
      However, the formation of the gammacerane derivative tetrahymanol, which is
      produced in addition to hopanoids in B. japonicum strains in vivo, could not be
      detected in vitro. Therefore, the presence of a second squalene cyclase in B.
      japonicum can be assumed. Sequence analysis of 0.5 kb upstream from the shc gene
      identified a partial ORF with significant similarity to the C-terminus of an ORF
      located immediately upstream from the shc gene in Z. mobilis. Both ORFs also
      showed similarity to phytoene desaturases from cyanobacteria and plants. The 3'
      end of this ORF from B. japonicum overlaps with 13 bp at the 5'-end of shc. The
      close proximity of this ORF to shc suggests that shc and this ORF may be part of
      an operon.

PMID- 9141687
TI  - Amplification of a Streptomyces lividans 4.3 kb DNA element causes overproduction
      of a novel hypha- and vesicle-associated protein.
AB  - The wild-type Streptomyces lividans 66 genome contains a 4.3 kb amplifiable DNA
      unit (AUD), and its four ORFs encode proteins that could not be identified by
      sequence comparison with databases. One of the gene products (encoded by orf-2)
      was purified and determined to be a novel 23 kDa protein. This protein is
      synthesized by the wild-type strain, absent in a variant lacking the AUD and
      overproduced in a variant in which the AUD is amplified (ADS). Immunological
      studies and analyses by confocal laser microscopy showed that the 23 kDa protein
      is associated with the substrate hyphae of the wild-type and the ADS-containing
      variant. Examination by microscopy revealed that the strain carrying the ADS
      forms bulges within the substrate hyphae and apical vesicles. These bulges have
      high levels of associated 23 kDa protein and contain storage-like material.

PMID- 9141688
TI  - Use of an excision reporter plasmid to study the intracellular mobility of the
      conjugative transposon Tn916 in gram-positive bacteria.
AB  - An excision reporter plasmid was constructed to characterize the intracellular
      mobility of Tn916 in various Gram-positive bacteria. The reporter component of
      this plasmid is a chloramphenicol-resistance gene which has been insertionally
      inactivated with the integrative vector pAT112 containing the attachment site of
      Tn916. Tn916-mediated excision of pAT112, to produce clones resistant to
      chloramphenicol, was detected in Enterococcus faecalis BM4110, Listeria
      monocytogenes L028-Str and Streptococcus gordonii BM120, but not in Lactococcus
      lactis MG1363-RF or in Streptococcus pneumoniae BM124, and always depended upon
      the ability of the bacterial host to generate circular forms of the transposon.
      The results suggest that (i) the excision event, although required, is not
      sufficient for conjugal transfer to occur and (ii) there is no linear
      relationship between the donor potential of E. faecalis strains and either the
      excision frequency of pAT112 or the copy number of Tn916 circular intermediates
      per cell in these hosts. Excision of pAT112 occurred mainly during the late
      exponential phase of growth of E. faecalis and L. monocytogenes and this
      recombination event was not stimulated by heat shock, salt and alcohol stresses
      or by the presence of tetracycline in the medium.

PMID- 9141689
TI  - The TBP gene from Aspergillus nidulans-structure and expression in Saccharomyces
      cerevisiae.
AB  - The genomic and cDNA copy of the TATA-binding protein (TBP) gene from the
      filamentous fungus Aspergillus nidulans have been cloned. The gene is interrupted
      by four introns, one of which is in the long 5' untranslated region of 615 bp.
      The transcription initiation site was established and the levels of mRNA were
      analysed under diverse growth conditions and found to vary severalfold. The gene
      encodes a protein of 268 amino acids composed of an N-terminal domain of 88 amino
      acids with no significant homology to other TBPs and a C-terminal domain of 180
      amino acids with about 95% homology to other fungal TBPs. A cDNA clone under the
      yeast ADH1 promoter was able to substitute for the yeast TBP gene in vivo;
      however, the transformants obtained grew poorly at 35 degrees C and on galactose
      and glycerol at 30 degrees C, though they could grow in the presence of copper
      ions or aminotriazole at this temperature. This phenotype may be the result of
      altered function of A. nidulans TBP in certain yeast transcription activation
      pathways.

PMID- 9141690
TI  - Genes encoding the NAD-reducing hydrogenase of Rhodococcus opacus MR11.
AB  - The dissociation of the soluble NAD-reducing hydrogenase of Rhodococcus opacus
      MR11 into two dimeric proteins with different catalytic activities and cofactor
      composition is unique among the NAD-reducing hydrogenases studied so far. The
      genes of the soluble hydrogenase were localized on a 7.4 kbp Asnl fragment of the
      linear plasmid pHG201 via heterologous hybridization. Analysis of the nucleotide
      sequence of this fragment revealed the seven open reading frames ORF1, hoxF, -U, 
      Y, -H, -W and ORF7. The six latter ORFs belong to the gene cluster of the soluble
      hydrogenase. Their gene products are highly homologous to those of the NAD
      reducing enzyme of Alcaligenes eutrophus H16. The genes hoxF, -U, -Y and -H
      encode the subunits alpha, gamma, delta and beta, respectively. The gene hoxW
      encodes a putative protease, which may be essential for C-terminal processing of
      the beta subunit. Finally, ORF7 encodes a protein which has similarities to cAMP-
      and cGMP-binding protein kinases, but its function is not known. ORF1, which lies
      upstream of the hydrogenase gene cluster, encodes a putative transposase found in
      IS elements of other bacteria. Northern hybridizations and primer extensions
      using total RNA of autotrophically and heterotrophically grown cells of R. opacus
      MR11 indicated that the hydrogenase genes are under control of a delta 70-like
      promoter located at the right end of ORF1 and are even transcribed under
      heterotrophic conditions at a low level. Furthermore, this promoter was shown to
      be active in the recombinant Escherichia coli strain LHY1 harbouring the 7.4 kbp
      Asnl fragment, resulting in overexpression of the hydrogenase genes. Although all
      four subunits of the soluble hydrogenase were shown via Western immunoblots to be
      synthesized in E. coli, no active enzyme was detectable.

PMID- 9141691
TI  - Structure and gene-polypeptide relationships of the region encoding glycerol
      diffusion facilitator (glpF) and glycerol kinase (glpK) of Pseudomonas
      aeruginosa.
AB  - The glycerol facilitator is one of the few known examples of bacterial solute
      transport proteins that catalyse facilitated diffusion across the cytoplasmic
      membrane. A second protein, glycerol kinase, is involved in entry of external
      glycerol into cellular metabolism by trapping glycerol in the cytoplasm as sn
      glycerol 3-phosphate. Evidence is presented that glycerol transport in
      Pseudomonas aeruginosa is mediated by a similar transport system. The genes
      encoding the glycerol facilitator, glpF, and glycerol kinase, glpK, were isolated
      on a 4.5 kb EcoRI fragment from a chromosomal mini-library by functional
      complementation of an Escherichia coli glpK mutant after establishing a map of
      the chromosomal glpFK region with the help of a PCR-amplified glpK segment. The
      nucleotide sequence revealed that glpF is the promoter-proximal gene of the glpFK
      operon. The glycerol facilitator and glycerol kinase were identified in a T7
      expression system as proteins with apparent molecular masses of 25 and 56 kDa,
      respectively. The identities of the glycerol facilitator and glycerol kinase
      amino acid sequences with their counterparts from Escherichia coli were 70 and
      81%, respectively; this similarity extended to two homologues in the genome
      sequence of Haemophilus influenzae. A chromosomal delta glpFK mutant was isolated
      by gene replacement. This mutant no longer transported glycerol and could no
      longer utilize it as sole carbon and energy source. Two ORFs, orfX and orfY,
      encoding a putative regulatory protein and a carbohydrate kinase of unknown
      function, were located upstream of the glpFK operon.

PMID- 9141692
TI  - The temperature sensitivity of Bacillus subtilis DB1005 is due to insufficient
      activity, rather than insufficient concentration, of the mutant delta A factor.
AB  - The delta A factor of Bacillus subtilis DB1005 contains two amino acid
      substitutions (I198A and I202A) in the promoter-10 binding region. It has been
      confirmed that this delta factor is responsible for the temperature sensitivity
      of B. subtilis DB1005. An investigation was conducted into how the mutant delta A
      could cause temperature-sensitive (Ts) cell growth by analysing its structural
      stability, cellular concentration and transcriptional activity. The mutant delta
      A was unstable even at the permissive temperature of 37 degrees C (t1/2 59 min),
      whereas the wild-type counterpart was fairly stable under the same conditions
      (t1/2 > 600 min). However, neither wild-type delta A nor mutant delta A was
      stable at 49 degrees C (t1/2 34 min and 23 min, respectively). Analyses of the
      rates of delta A synthesis revealed that B. subtilis DB1005 was able to
      compensate for unstable delta A by elevating the level of delta A at 37 degrees C
      but not at 49 degrees C. Moreover, overexpression of the mutant delta A at 49
      degrees C could not suppress the Ts phenotype of B. subtilis DB1005. This
      indicates that the temperature sensitivity of B. subtilis DB1005 is not due to
      insufficient delta A concentration in the cell. The greater decline of an already
      reduced activity of the mutant delta A at 49 degrees C suggests that the
      temperature sensitivity of B. subtilis DB1005 is instead the result of a very low
      activity of delta A; probably below a critical level necessary for cell growth.

PMID- 9141693
TI  - The Bacillus subtilis clpC operon encodes DNA repair and competence proteins.
AB  - ClpC of Bacillus subtilis, controlling competence gene expression and survival
      under stress conditions, is encoded by the fourth gene of a six-gene operon. The
      product of orf1 contains a potential helix-turn-helix motif, but shows no
      significant similarities with known protein sequences. The second and third genes
      encode proteins with similarities to zinc-finger proteins (orf2) and arginine
      kinases (orf3), respectively. The product of orf5 contains a zinc-finger motif
      and an ATP-binding domain, and is highly similar to the product of the
      Escherichia coli sms gene. A strain bearing a disruption of orf5 showed increased
      sensitivity to the alkylating agent methyl methanesulfonate. Furthermore, this
      mutant strain displayed decreased capacity for genetic recombination as measured
      by transformation experiments. The last open reading frame, orf6, encodes a
      protein with limited similarity in its C-terminal part to the B. subtilis comEA
      gene product and to the UvrC DNA repair excinuclease. Inactivation of orf5
      resulted in strongly diminished transformation with all types of DNA. Mutations
      affecting either orf5 or orf6 resulted in strains with decreased resistance to UV
      irradiation in the stationary phase, indicating that these proteins play a role
      in the development of a non-specific stationary-phase resistance to UV
      irradiation. Moreover, these results suggest an involvement of both proteins in
      transformation and presumably in DNA repair.

PMID- 9141694
TI  - A 23.4 kb segment at the 69 degrees-70 degrees region of the Bacillus subtilis
      genome.
AB  - Within the framework of the international project aimed at the sequencing of the
      Bacillus subtilis genome, a 23.4 kb chromosome segment has been cloned and
      sequenced. This region (23 433 bp; 69 degrees-70 degrees of the genetic map)
      contains 17 complete ORFs and a partial one. A homology search for the products
      deduced from the 18 ORFs revealed that twelve of them had significant similarity
      to known proteins, including the quinolone-resistance protein, ABC transporter,
      aldehyde dehydrogenase, amino acid transporter, fosmidomycin-resistance protein,
      CDP-glucose 4,6-dehydratase, glucose-1-phosphate cytidyltransferase and
      cytochrome P450/NADPH-cytochrome P450 reductase.

PMID- 9141695
TI  - A 23911 bp region of the Bacillus subtilis genome comprising genes located
      upstream and downstream of the lev operon.
AB  - Within the framework of the European project to sequence the whole Bacillus
      subtilis 168 genome, a 23911 bp long chromosomal DNA fragment located around 233
      degrees on the B. subtilis genetic map was cloned and sequenced. From the
      generated sequencing data and the results of the homology search, the primary
      structure of this region was determined. In addition to the whole lev operon, the
      region contains putative genes for an amino acid permease, two different alcohol
      dehydrogenases, a chitosanase, a protein belonging to the LysR family of
      transcriptional regulators, a protein related to the MerR transcriptional
      regulator, up to four proteins related to the product of the spoF gene, and genes
      coding for nine more inferred proteins of unknown function.

PMID- 9141696
TI  - The signal peptidase II (Isp) gene of Bacillus subtilis.
AB  - The gene encoding the type II signal peptidase (SPase II) of Bacillus subtilis
      was isolated by screening a genomic DNA library of this bacterium for the ability
      to increase the levels of globomycin resistance in Escherichia coli, and to
      complement the growth deficiency at the non-permissive temperature of E. coli
      strain Y815 carrying a temperature-sensitive mutation in its Isp gene for SPase
      II. The deduced amino acid sequence of the B. subtilis SPase II showed
      significant similarity with those of other known SPase II enzymes. Activity of
      the B. subtilis SPase II was demonstrated by a pulse-labelling experiment in E.
      coli. In B. subtilis, the Isp gene is flanked by the isoleucyl-tRNA synthetase
      (ileS) gene and the pyrimidine biosynthetic (pyr) gene cluster, which is known to
      map at 139 degrees of the chromosome. In the Gram-positive bacteria studied thus
      far, Isp appears to be the first gene in an operon. The promoter-distal gene
      ("orf4') of this operon specifies a hypothetical protein in bacteria and yeast.

PMID- 9141697
TI  - Analysis of the genetic polymorphism between three Streptococcus thermophilus
      strains by comparing their physical and genetic organization.
AB  - The physical maps of Streptococcus thermophilus CNRZ368 and NST2280 strains were
      constructed by analysing PFGE patterns obtained with the low-frequency-cutting
      enzymes SmaI, BssHII and SfiI. Their chromosomes are 1864 and 1840 kb circular
      molecules, respectively. Comparison of their physical maps with that of the
      reference A054 strain revealed a relatively conserved organization of the
      restriction sites. Three variable regions were detected with the map of CNRZ368
      whereas 15 were found with the map of NST2280. To construct the genetic maps,
      probes corresponding to 10 single-copy genes, the rrn genes and the insertion
      sequences IS1191, IS981 and ISS1 were hybridized to Southern blots of chromosomal
      DNA digested with the different mapping enzymes. Comparison of the genetic maps
      of the three strains showed a conserved location of the mapped single-copy genes.
      However, six rrn loci were present in the chromosome of A054 and CNRZ368 whereas
      five were present in the NST2280 chromosome. A polymorphism was also found in the
      copy number of the insertion sequences between the three strains.

PMID- 9141698
TI  - Directed introduction of DNA cleavage sites to produce a high-resolution genetic
      and physical map of the Acinetobacter sp. strain ADP1 (BD413UE) chromosome.
AB  - The natural transformability of the soil bacterium Acinetobacter sp. ADP1
      (BD413UE), formerly classified as A. calcoaceticus, has facilitated previous
      physiological and biochemical investigations. In the present studies, the natural
      transformation system was exploited to generated a physical and genetic map of
      this strain's 3780 +/- 191 kbp circular chromosome. Previously isolated
      Acinetobacter genes were modified in vitro to incorporate a recognition sequence
      for the restriction endonuclease NotI. Following transformation of the wild-type
      strain by the modified DNA, homologous recombination placed each engineered NotI
      cleavage site at the chromosomal location of the corresponding gene. This allowed
      precise gene localization and orientation of more than 40 genes relative to a
      physical map which was constructed with transverse alternating field
      electrophoresis (TAFE) and Southern hybridization methods. The positions of NotI,
      AscI and I-CeuI recognition sites were determined, and the latter enzyme
      identified the presence of seven ribosomal RNA operons. Multiple chromosomal
      copies of insertion sequence IS1236 were indicated by hybridization. Several of
      these copies were concentrated in one region of the chromosome in which a
      spontaneous deletion of approximately 100 kbp occurred. Moreover, contrary to
      previous reports, ColE1-based plasmids appeared to replicate autonomously in
      Acinetobacter sp. ADP1.

PMID- 9141699
TI  - Molecular characterization of the bet genes encoding glycine betaine synthesis in
      Sinorhizobium meliloti 102F34.
AB  - As a first step towards the elucidation of the molecular mechanisms responsible
      for the utilization of choline and glycine betaine (betaine) either as carbon and
      nitrogen sources or as osmoprotectants in Sinorhizobium meliloti, we selected a
      Tn5 mutant, LTS23-1020, which failed to grow on choline but grew on betaine. The
      mutant was deficient in choline dehydrogenase (CDH) activity, failed to oxidize
      [methyl-14C]choline to [methyl-14C]betaine, and did not use choline, but still
      used betaine, as an osmoprotectant. The Tn5 mutation in LTS23-1020 was
      complemented by plasmid pCHO34, isolated from a genomic bank of S. meliloti
      102F34. Subcloning and DNA sequencing showed that pCHO34 harbours two ORFs which
      showed 60% and 57% identity with the Escherichia coli betB gene encoding betaine
      aldehyde dehydrogenase (BADH) and betA gene encoding CDH, respectively. In
      addition to the homology with E. coli genes, the deduced sequence of the
      sinorhizobial BADH protein displays consensus sequences also found in plant
      BADHs. The deduced sequence of the sinorhizobial CDH protein shares only 21%
      identical residues with choline oxidase from Arthrobacter globiformis. The
      structural organization of the betBA genes in S. meliloti differs from that
      described in E. coli: (i) the two ORFs are separated by a 210 bp sequence
      containing inverted repeats resembling a putative rho-independent transcription
      terminator, and (ii) no sequence homologous to betT (high-affinity choline
      transport system) or betI (regulator) was found in the vicinity of the
      sinorhizobial betBA genes. Evidence is also presented that the S. meliloti betBA
      genes are not located on the megaplasmids.

PMID- 9141700
TI  - The soybean cultivar specificity gene nolX is present, expressed in a nodD
      dependent manner, and of symbiotic significance in cultivar-nonspecific strains
      of Rhizobium (Sinorhizobium) fredii.
AB  - Rhizobium (now Sinorhizobium) fredii is a symbiotic nitrogen-fixing bacterium
      that can nodulate soybean in a cultivar-specific manner. This process is governed
      by a set of negatively acting nodulation genes termed nolXWBTUV. These genes
      prevent R. fredii strain USDA257 from infecting soybean cultivars such as McCall,
      but they do not block nodulation of cultivar Peking. R. fredii strain USDA191
      contains DNA sequences that hybridize to nolXWBTUV, yet it forms normal nitrogen
      fixing nodules on both McCall and Peking soybean. These sequences were isolated
      and their structure and function examined in comparison to nolXWBTUV of strain
      USDA257. Restriction maps of the two loci are identical, as is a 2-4 kb DNA
      sequence that corresponds to nolX and its promoter region. Expression of nolX by
      strain USDA191 is flavonoid-dependent in culture and readily detectable in
      nodules. The gene is not inducible in a mutant of strain USDA191 that lacks the
      regulatory nodD1 gene, and its expression is greatly attenuated in a nodD2
      mutant. nolX is also present and flavonoid-inducible in HH103, a second R. fredii
      strain that nodulates McCall soybean normally. Inactivation of nolX in strain
      HH103, USDA191 or USDA257 leads to retardation of initial nodulation rates on
      soybean cultivars such as Peking and to acquisition of the capacity to form
      nitrogen-fixing nodules on two species of Erythrina. nolX is thus of symbiotic
      significance in all three strains, even though it regulates soybean cultivar
      specificity only in strain USDA257.

PMID- 9141701
TI  - Identification of genes in Rhizobium leguminosarum bv. trifolii whose products
      are homologues to a family of ATP-binding proteins.
AB  - The specific interaction between rhizobia and their hosts requires many genes
      that influence both early and late steps in symbiosis. Three new genes,
      designated prsD, prsE (protein secretion) and orf3, were identified adjacent to
      the exo133 mutation in a cosmid carrying the genomic DNA of Rhizobium
      leguminosarum bv. trifolii TA1. The prsDE genes share significant homology to the
      genes encoding ABC transporter proteins PrtDE from Erwinia chrysanthemi and AprDE
      from Pseudomonas aeruginosa which export the proteases in these bacteria. PrsD
      shows at least five potential transmembrane hydrophobic regions and a large
      hydrophilic domain containing an ATP/GTP binding cassette. PrsE has only one
      potential transmembrane hydrophobic domain in the N-terminal part and is proposed
      to function as an accessory factor in the transport system. ORF3, like PrtF and
      AprF, has a typical N-terminal signal sequence but has no homology to these
      proteins. The insertion of a kanamycin resistance cassette into the prsD gene of
      the R. leguminosarum bv. trifolii TA1 wild-type strain created a mutant which
      produced a normal amount of exopolysaccharide but was not effective in the
      nodulation of clover plants.

PMID- 9141702
TI  - A secreted aspartic proteinase from Glomerella cingulata: purification of the
      enzyme and molecular cloning of the cDNA.
AB  - A secreted aspartic proteinase from Glomerella cingulata (GcSAP) was purified to
      homogeneity by ion exchange chromatography. The enzyme has an M, of 36000 as
      estimated by SDS-PAGE, optimal activity from pH 3.5 to pH 4.0 and is inhibited by
      pepstatin. The N-terminal sequence, 23 residues long, was used to design a gene
      specific primer. This was used in 3' RACE (rapid amplification of cDNA ends) PCR
      to amplify a 1.2 kb fragment of the gcsap cDNA. A second gene-specific primer was
      designed and used in 5' RACE PCR to clone the 5' region. This yielded a 600 bp
      DNA fragment and completed the open reading frame. The gcsap open reading frame
      encodes a protein with a 78 residue prepro-sequence typical of other fungal
      secreted aspartic proteinases. Based on the deduced sequence, the mature enzyme
      contains 329 amino acids and shows approximately 40% identity to other fungal
      aspartic proteinases. Subsequent cloning and sequencing of gcsap fragments
      obtained from PCR with genomic DNA revealed a 73 bp intron beginning at nt 728.
      Southern analyses at medium and high stringency indicated that G. cingulata
      possesses one gene for the secreted aspartic proteinase, and Northern blots
      indicated that gene expression was induced by exogenous protein and repressed by
      ammonium salts. GcSAP is a putative pathogenicity factor of G. cingulata, and it
      will now be possible to create SAP-mutants and assess the role GcSAP plays in
      pathogenicity.

PMID- 9141703
TI  - Homologous regions of the Salmonella enteritidis virulence plasmid and the
      chromosome of Salmonella typhi encode thiol: disulphide oxidoreductases belonging
      to the DsbA thioredoxin family.
AB  - The nucleotide sequence relatedness between the chromosome of Salmonella typhi
      and the virulence plasmid of Salmonella enteritidis was investigated using short
      DNA probes of < 2 kb covering the whole virulence plasmid sequence. Only one
      homologous region was detected. This region was subsequently cloned and partially
      sequenced. Sequences closely related to the pefl gene and the ORFs orf7, orf8 and
      orf9, which are located downstream of the fimbrial pef operon of the Salmonella
      typhimurium virulence plasmid, were detected. Sequencing of the cloned S. typhi
      DNA fragment also revealed identity with genes of the fimbrial sef operon
      characterized in the chromosome of S. enteritidis. These nucleotide sequences
      mapped upstream of the S. typhi chromosomal region homologous to the S.
      enteritidis virulence plasmid. The general organization of the cloned S. typhi
      chromosomal fragment was similar to the fimbriae-encoding region of the S.
      typhimurium virulence plasmid. The deduced product of orf8 in the S. typhimurium
      virulence plasmid, as well as those of the corresponding ORFs in the homologous
      region of the S. typhi chromosome and in the S. enteritidis virulence plasmid
      (designated dlt and dlp, respectively), appeared to be related to the thioredoxin
      family of thiol: disulphide oxidoreductases. The dlp gene was able to complement
      the DTT-sensitive phenotype, the inability to metabolize glucose 1-phosphate and
      the low alkaline phosphatase activity of a dsbA mutant of Escherichia coli. The
      dlt gene partially complemented the lack of alkaline phosphatase activity, but
      not the other mutant phenotypes. The products of both genes could be detected
      using the T7 RNA polymerase promoter expression system. The estimated molecular
      masses of the products of the dlt and dlp genes by SDS-PAGE were 26 and 23 kDa,
      respectively, the first being in agreement with the deduced amino acid sequence
      and the latter, somewhat smaller. The processing of a possible leader peptide in
      the Dlp protein, but not in the Dlt protein, could be responsible for this
      difference. The Dlp protein appeared as a doublet band on SDS-PAGE, which is
      characteristic of the oxidized and reduced states of this kind of protein.

PMID- 9141704
TI  - Variation within serovars of Neisseria gonorrhoeae detected by structural
      analysis of outer-membrane protein PIB and by pulsed-field gel electrophoresis.
AB  - Outer-membrane protein PI is the antigen responsible for serovar specificity of
      Neisseria gonorrhoeae and is a potential vaccine target. In order to investigate
      possible hidden variation within a serovar, the sequence of the por genes
      encoding protein PIB have been obtained from a series of strains, including
      isolates known to be epidemiologically linked. The inferred amino acid sequences
      of the PIB molecules of isolates from known sexual contacts were identical, but
      non-related isolates showed significant heterogeneity in PIB sequence. These
      differences were not confined to the two variable regions (Var1 and Var2) which
      have previously been identified, but were largely, although not exclusively,
      located in regions predicted to form one of eight surface-exposed loops. The
      isolates were subjected to pulsed-field gel electrophoresis of restriction
      digests of chromosomal DNA, which also demonstrated identity between linked
      strains but revealed diversity within a serovar. The deduced amino acid sequences
      of PIB were also used to synthesize peptides for epitope-mapping experiments.
      These revealed that some mAbs, used to define serovar specificity, recognized
      linear epitopes located in loops 5 and 6, while others appeared to recognize
      conformational epitopes elsewhere in the molecule. The occurrence of the sequence
      differences within a serovar, which are not detected by the serotyping reagents,
      reveals that PIB represents a potential source of information which should permit
      considerably more detailed epidemiological studies than are currently possible
      and focuses attention on more conserved regions of the protein as potential
      targets for vaccination.

PMID- 9141705
TI  - Differences in genetic diversity of nonecapsulated Haemophilus influenzae from
      various diseases.
AB  - Genetic relationships among 80 isolates of nonencapsulated Haemophilus influenzae
      recovered from different disease types were determined by multilocus enzyme
      electrophoresis (MEE) at 13 enzyme loci in an attempt to assess the association
      between multilocus genotype and disease. The isolates were obtained from 15
      patients with meningitis, 10 with otitis media, 19 with chronic bronchitis, 20
      with cystic fibrosis, and 16 were obtained from healthy carriers. The 80 isolates
      were assigned to 69 electrophoretic types (ETs) falling into 5 groups. Isolates
      from each disease entity were represented by a variety of genotypes; however,
      cluster analysis from a matrix of genetic distances between ETs revealed that the
      ETs of the otitis media and meningitis isolates were all clustered within a
      genetic distance of 0.55 (group I). In addition, no genotypes were shared between
      H. influenzae carrier isolates and isolates from cases of disease, H. influenzae
      isolates from healthy individuals were distributed significantly differently from
      those from chronic bronchitis meningitis and otitis media patients. The genetic
      diversity (H) of carrier strains was greatest, although not statistically
      different from that of isolates from patients with disease. It was concluded that
      the genetic distribution of acute disease isolates is not random over the five ET
      groups, although the genetic diversity within the groups is not different. The
      effect of bacterial persistence in the host on the genetic diversity of H.
      influenzae is discussed.

PMID- 9141706
TI  - Antigenic polymorphism of the lipopolysaccharides from human and animal isolates
      of Bordetella bronchiseptica.
AB  - Six monoclonal antibodies (mAbs) against lipopolysaccharides (LPS) from
      Bordetella pertussis (P1P3, 60.5), B. parapertussis (PP2, PP6, PPB) and B.
      bronchiseptica (BRg1) were used to examine the presence of antigenic determinants
      of LPS on B. bronchiseptica cells. Forty-eight clinical isolates of this Gram
      negative bacterium (4 canine, 3 equine, 6 porcine, 4 rabbit and 31 human) were
      examined. Significant cross-reactivities with the heterologous anti-pertussis and
      anti-parapertussis mAbs were observed. The isolates also exhibited marked
      antigenic polymorphism. The 48 isolates could be classified in six immunogroups.
      Purified LPS preparations extracted from some isolates were analysed by ELISA,
      thin-layer chromatography, and tricine-SDS-PAGE. The results show that four main
      types of antigenic polymorphism of B. bronchiseptica LPSs exist: (a)
      heterogeneity of the core, (b) presence or absence of O-chains, (c) differences
      in the hinge region between O-chain and core, and (d) differences in interactions
      of LPS with other cell-surface constituents. Smooth-type LPS molecules,
      detectable with mAb PP6, were more frequently observed in animal isolates (94%)
      than in human isolates (52%). Reverse frequencies were found with mAb 60.5 (48%
      of human isolates, 18% of animal isolates), which is unable to react with long
      chain LPSs. This observation could be due to the general absence of some lectin
      like receptor, specific to the O-chain, on human bronchoalveolar tissues.

PMID- 9141707
TI  - Phylogeny of cyanobacterial nifH genes: evolutionary implications and potential
      applications to natural assemblages.
AB  - DNA sequences of a fragment of nifH from diverse cyanobacteria were amplified,
      cloned and sequenced to determine the evolutionary relationship of nitrogenase
      within the cyanobacteria as a group, and to provide a basis for the
      identification of uncultivated strains of cyanobacteria in the environment.
      Analysis of 30 nitrogenase DNA and deduced amino acid sequences from
      cyanobacteria representing five major taxonomic subdivisions showed great
      variation in phylogenetic distances between the sequences. Sequences from
      heterocystous cyanobacteria formed a coherent cluster, in which branching forms
      did not form a clade distinct from the non-branching forms. Nitrogenase sequences
      from the unicellular cyanobacteria Gloeothece and Synechococcus sp. RF-1 formed a
      cluster, as did sequences from the genera Xenococcus and Myxosarcina. The nifH
      sequences of filamentous nonheterocystous cyanobacteria were not closely related
      to each other, forming deep branches with respect to the heterocystous
      cyanobacterial nifH sequences. The phylogeny of nifH based on amino acid
      sequences was consistent with taxonomic relationships among the strains; for
      example, a sequence obtained form a natural assemblage believed to be dominated
      by 'Lyngbya' clustered with nifH from Lyngbya lagerheimii. Results also indicate
      that the phylogeny of nifH among the cyanobacteria is largely consistent with the
      phylogeny of 16S rRNA, and furthermore that the nifH sequence can be used to
      identify uncultivated strains of nitrogen-fixing cyanobacteria.

PMID- 9141708
TI  - Methylosphaera hansonii gen. nov., sp. nov., a psychrophilic, group I
      methanotroph from Antarctic marine-salinity, meromictic lakes.
AB  - Methanotrophic bacteria were enumerated and isolated from the chemocline and
      surface sediments of marine-salinity Antarctic meromictic lakes located in the
      Vestfold Hills, Antarctica (68 degrees S 78 degrees E). Most probable number
      (MPN) analysis indicated that at the chemocline of Ace Lake the methanotroph
      population made up only a small proportion of the total microbial population and
      was sharply stratified, with higher populations detected in the surface sediments
      collected at the edge of Ace Lake and Burton Lake. Methanotrophs were not
      detected in Pendant Lake. Only a single phenotypic group of methanotrophs was
      successfully enriched, enumerated and isolated into pure culture from the lake
      samples. Strains of this group were non-motile, coccoidal in morphology, did not
      form resting cells, reproduced by constriction, and required seawater for growth.
      The strains were also psychrophilic, with optimal growth occurring at 10-13
      degrees C and maximum growth temperatures of 16-21 degrees C. The ribulose
      monophosphate pathway but not the serine pathway for incorporation of C1
      compounds was detectable in the strains. The guanine plus cytosine (G + C)
      content of the genomic DNA was 43-46 mol%. Whole-cell fatty acid analysis
      indicated that 16:1 omega 8c (37-41%), 16:1 omega 6c (17-19%), 16:1 omega 7c (15
      19%) and 16:0 (14-15%) were the major fatty acids in the strains. 16s rDNA
      sequence analysis revealed that the strains form a distinct line of descent in
      the family Methylococcaceae (group I methanotrophs), with the closest relative
      being the Louisiana Slope methanotrophic mytilid endosymbiont (91.8-92.3%
      sequence similarity). On the basis of polyphasic taxonomic characteristics the
      Antarctic lake isolates represent a novel group I methanotrophic genus with the
      proposed name Methylosphaera hansonii (type strain ACAM 549).

PMID- 9141709
TI  - Use of multilocus enzyme electrophoresis to examine genetic relationships amongst
      isolates of Mycobacterium intracellulare and related species.
AB  - As part of a larger study investigating diversity and distribution of
      Mycobacterium spp. in Australia, multilocus enzyme electrophoresis was used to
      assess genetic relationships at 17 enzyme loci amongst a collection of reference
      strains and isolates initially identified on biochemical and other grounds as M.
      intracellulare (70), "X' mycobacteria (10), M. scrofulaceum (7), M. avium (8) and
      M. avium subsp. paratuberculosis (2). Two of the isolates initially identified as
      M. intracellulare were shown to be quite distinct from the others. Both gave
      negative results in a species-specific DNA probe test, whilst one was positive by
      PCR. These results emphasize the uncertainties involved in identifying members of
      this group. The other M. intracellulare isolates formed a cohesive but diverse
      group, being divided into 48 electrophoretic types (ETs), with a mean genetic
      diversity of 0.38. Forty-three of these ETs contained only single isolates. There
      was no clear relationship between the serovar and ET designation. The index of
      association calculated for M. intracellulare was significantly different from
      zero, suggesting that it is a clonal species. PFGE was also applied to selected
      isolates from the ETs containing multiple isolates, and some of these could be
      differentiated further. The strains of M. scrofulaceum and "X' mycobacteria were
      distinct from M. intracellulare, but themselves were highly heterogeneous, with
      mean genetic diversities of 0.66 and 0.65, respectively. Each of these groups may
      represent more than one species. M. avium strains were distinct from the two M.
      avium subsp. paratuberculosis strains, as well as from the other mycobacteria
      studied.

PMID- 9141710
TI  - Genomic relationships between selected phage types of Salmonella enterica subsp.
      enterica serotype typhimurium defined by ribotyping, IS200 typing and PFGE.
AB  - The genomic relationship between isolates representing 17 definitive phage types
      (DTs) of Salmonella enterica subsp. enterica serotype typhimurium (S.
      typhimurium) were analysed using three different typing methods: IS200 typing
      using the restriction enzymes EcoRI and PvuII, ribotyping using SmaI and EcoRI,
      and PFGE using XbaI. These methods were used to study four DTs in greater detail;
      in all 18 (DT 49), 10 (DT 110), five (DT 120) and seven (DT 135) isolates were
      studied. The combined data generated two large clusters, which could be divided
      into five groups. Within the first cluster, a close similarity was indicated
      between isolates of the following phage types: group A-DTs 44, 49, 135 and 204c,
      with DT 9 distantly related; group B-DTs 95 and 99; and group C-DTs 104a, 110 and
      120. The other large cluster contained group D-DTs 10, 20 and 146, with DT 12
      distantly related, and group E-DTs 69, 103 and 153. The same grouping was
      observed by principal component analysis, but a minimum spanning tree linked DT
      12 to group E and not group D in this analysis. Among the typing methods used,
      IS200 gave the best representation of the overall similarity between the S.
      typhimurium isolates. Five different IS200 profiles were obtained among isolates
      belonging to DT 49. Only one profile was observed within each of the phage types
      DT 110, 120 and 135. All isolates within each of these four phage types were of
      one ribotype. Isolates of DT 49 showed four PFGE patterns, while one pattern was
      present within isolates of the three other phage types. Members of these four
      phage types were found to be clonally related as they formed tight subclusters
      separated from isolates of other phage types.

PMID- 9141711
TI  - Seroepidemiology of measles, mumps and rubella virus infections in normal
      children and adults in southern Granada, Spain: response to a vaccination
      programme.
AB  - A seroepidemiological study of measles, mumps and rubella virus infection in
      normal children and adults in southern Granada, Spain, and the response to a
      vaccination programme was carried out. Protection from the mumps and rubella
      virus was reduced in the group of 3 to 7 year-old children vaccinated at age 15
      months indicating the need for revaccination against rubella as well as the mumps
      virus.

PMID- 9141712
TI  - Differentiation of Acinetobacter baumannii biotypes by amplification of 16S-23S
      rRNA intergenic spacer sequences.
AB  - Isolates of Acinetobacter baumannii (32 strains) from blood samples obtained from
      patients in five Chilean hospitals were identified and biotyped according to
      their phenotypic properties. They were also submitted to random amplified
      polymorphic DNA (RAPD) using eight randomly designed 10-mers and the core
      sequence of M13 phage (15-mers) as well as amplification of the spacer regions
      between 16S and 23S genes in the prokaryotic rRNA genetic loci. With some
      primers, RAPD discriminated between biotypes, whereas with others each isolate
      showed a particular profile. When amplification of spacer regions was performed,
      a clear correlation between patterns and biotypes was found. This last technique
      allowed correct biotyping of clinical isolates. Both genetic methods might be
      used for the identification of A. baumannii biotypes.

PMID- 9141713
TI  - Spontaneous binding of Vibrio cholerae to human leucocytes.
AB  - Various lymphocyte subpopulations have the capacity to bind different strains of
      Gram-negative bacteria. The capacity of a strain of Vibrio cholerae, biotype El
      Tor, isolated during an outbreak of cholera, to adhere to mononuclear cells
      isolated from peripheral blood was evaluated. V. cholerae binds to mononuclear
      cells in a dose-dependent manner. The binding was 76.1% at a cells/bacteria ratio
      of 1:200 and significantly decreased to 43.1% at a ratio of 1:1. The value of
      bound bacteria, a marker of the mean number of binding sites on the cell surface,
      decreased at lower cell/bacteria ratios. Studies on isolated cellular populations
      demonstrated that 51, 42 and 38%, respectively, of CD4+, CD8+ and B cells were
      bound by V. cholerae whereas monocytes exhibited a higher binding capacity. The
      data suggest that the percentage binding of V. cholerae to lymphocytes and
      monocytes was higher than the percentage found in previous studies with Gram
      negative bacteria such as Yersinia enterocolitica, and Salmonella, but similar to
      Helicobacter pylori. The findings indicate that V. cholerae possesses multiple
      'adhesins' such as fimbriae, flagella, haemagglutinins, lipopolysaccharides, and
      outer membrane proteins. The capacity to bind to blood lymphocytes may reflect
      the same capacity for the lymphocytes from the gastrointestinal associated
      lymphoid tissue. This cytoadherence may contribute to the uptake of V. cholerae
      from the gut and may contribute to activation of B cells and CD4+ lymphocytes.

PMID- 9141714
TI  - Major origin of mutagenicity of chlorinated drinking water in China: humic acid
      or pollutants.
AB  - Since Loper and Glatz (J. Toxicol. Environ. Health, 4:919-938;1978) discovered
      the presence of the mutagenicity in drinking water after chlorination in 1978,
      humic acid (HA) has been considered as an important source. But our research
      results show that only 1/8 of observed direct frameshift mutagenicity in tap
      water originated from chlorination of HA isolated from raw water. Contamination
      from industrial waste and human settlement (night soil) are important potential
      sources of mutagenicity in chlorinated drinking water. The results show that
      mutagenicity from night soil after chlorination depended upon pH of sample.
      Production of mutagenicity at pH 6 is ten times of that at pH 8, and
      decomposition process is necessary condition for mutagenicity production. Season
      variation of mutagenicity of tap is also presented in the paper.

PMID- 9141715
TI  - The efficiency of removal of lead and other elements from domestic drinking
      waters using a bench-top water filter system.
AB  - The efficiency of removal of lead (Pb) and other elements from natural drinking
      waters using a bench-top water filter system was evaluated in three recently
      built houses in Sydney, Australia, and two from rural centres. In addition, one
      filter system was tested for copper (Cu), Pb and cadmium (Cd) under rigorously
      controlled laboratory conditions using Sydney water. For two Sydney houses, the
      efficiency was evaluated using special filter cartridges concomitant with the
      ordinary filters. Waters after passing through the filter, was sampled when the
      filter had been exposed to '0', 50, 100, 150, 200, and 250 l respectively and
      were analysed for lead isotopes and lead concentrations by high precision isotope
      dilution mass spectrometry. Samples that passed through the filter after '0', 50,
      150 and 250 l collections were analysed for four anions and 39 cations by various
      methods. Sydney water was fairly uniform in its anion and cation composition,
      whereas water from the two rural areas contained higher concentrations of Ca, Mg
      and HCO3. Effects of the filter on the water compositions can be summarised into
      three groups: (1) elements removed during filtration--Ca, Mg, Sr, Ba, Cu, Pb, Zn
      and Ni. With 'age' of the filter, the efficiency of removal for Pb was maintained
      in the two houses with Pb concentrations greater than 10 micrograms/l in the
      first flush water and was maintained for Cu through all concentrations. Ca, Mg,
      Sr and Ba were largely removed in the first 50 1 of usage. (2) Elements added
      during filtration--K, Rb, Ag and P. Except for Ag, which was present throughout
      the testing period, these elements were added only in the first filtration. (3)
      Elements unaffected by filtration--Al, Si, Na, Fe, Cl and F. Efficiency of Pb
      removal from tap water by this system depends generally on the initial Pb content
      in the water. However, it also seems to depend, to some extent, on Pb speciation
      and water composition, as found in earlier studies of natural waters. The control
      in filtering efficiency as a function of Pb speciation and chemical composition
      becomes more important at low initial Pb concentrations in the water. However,
      the Pb concentrations at which speciation and water composition appear to play a
      role in filter efficiency are so low that these factors, though scientifically
      interesting, have no relevance from a practical point of view, especially the
      impact on human health. Acidification of six sets of duplicate water samples, one
      sample immediately after collection and the other acidified after more than 2
      weeks, showed negligible changes in Pb or Cu concentrations between duplicates.

PMID- 9141716
TI  - Epicuticular wax variation in ecotypes of Arabidopsis thaliana.
AB  - Quantification of the epicuticular wax from the stems of 40 ecotypes of
      Arabidopsis thaliana showed a two-fold range in total wax load that was not
      correlated to known abiotic characteristics of the ecotype's origin of
      collection. Chemical analysis of these ecotypes revealed similar epicuticular wax
      profiles for all ecotypes except CT-1. In CT-1 the amount of 22 and 24 carbon
      length primary alcohols was increased by 16- and 8-fold, respectively, over that
      observed in the epicuticular wax averaged over all ecotypes.

PMID- 9141717
TI  - Dihydroisocoumarins from fungi: isolation, structure elucidation, circular
      dichroism and biological activity.
AB  - Five known and three new dihydroisocoumarins were isolated from different fungi.
      The new isocoumarins are 5-chloro-6-hydroxymellein, 5-chloro-4,6-dihydroxymellein
      and 5,6-dihydroxymellein. The absolute configuration of these secondary
      metabolites was confirmed by CD measurements and in two cases by X-ray structure
      analysis.

PMID- 9141718
TI  - Aboriginal drug and alcohol use: recent developments and trends.

PMID- 9141719
TI  - Hepatitis C and policy implementation: ethics as a dialogic process for resource
      allocation.

PMID- 9141720
TI  - 'Must it have been something I ate?'.

PMID- 9141721
TI  - Occupational health and safety: a model for public health?

PMID- 9141722
TI  - Narratives of risk in occupational health and safety: why the 'good' boss blames
      his tradesman and the 'good' tradesman blames his tools.
AB  - Risk and its control are important themes in occupational health and safety. In
      the current regulatory framework, risk is conceptualised as a probabilistic
      expression of hazard potential. However, social meanings of risk in the workplace
      may be different. The social context of work shapes the ways that risk is
      understood in the workplace, yet little research in occupational health and
      safety acknowledges it. A few studies of risk have used qualitative research
      methods to elicit understandings of risk at work; however, little research
      explores the experiences of both employers and employees. This study describes
      the narratives of risk in occupational health and safety of employers and
      employees in the Victorian painting industry. Using ethnographic methods, we
      collected data about the contexts in which risk is experienced and the sources of
      risk that each group identifies. These narratives reveal that risk in the
      painting industry is constructed through the interactions of three factors: the
      social context, the hierarchical structure of the industry and the shared
      assumptions about risk control through the individual skills and
      responsibilities. The narratives explain why occupational health and safety
      strategies focusing solely on individual behaviour change or technical measures
      will be unsuccessful.

PMID- 9141723
TI  - Knowledge of and attitudes to infection control of tattooists at registered
      premises in Victoria, 1994.
AB  - Historically, the relationship between health authorities and tattooists has been
      marked by suspicion and mutual distrust, with tattooists being stereotyped as
      having little concern for hygiene, and considered largely ineducable about
      infection control. In this study, a random sample of tattooists working at one
      third of the 65 registered tattooing premises in Victoria completed a
      questionnaire that recorded demographic information and knowledge and attitudes
      to Standards of practice for tattooing 1990, which specifies guidelines for
      infection control in Victorian tattooing premises. Of these premises, 89 per cent
      participated and 36 of 37 tattooists working therein (22 metropolitan, 14
      country) completed the questionnaire; 81 per cent were male. Reports by the
      tattooists indicated that: 50 per cent had not commenced immunisation for
      hepatitis B; that 78, 42 and 34 per cent either had not been tested or were
      unsure whether they had been tested for hepatitis C, hepatitis B and human
      immunodeficiency virus (HIV); and that no tattooist was a hepatitis B carrier or
      was positive for hepatitis C or HIV. Respondents acknowledged the potential for
      transmission of infectious diseases through tattooing, endorsed formal training
      in tattooing and infection control for new tattooists, and supported continuing
      education in infection control for existing tattooists. Most were critical of
      environmental health officers, particularly for inaction in not closing and
      prosecuting unregistered tattooists. Despite deficiencies in the knowledge and
      training of tattooists in infection control, they recognise its importance and
      are willing to attend appropriate training.

PMID- 9141724
TI  - Evaluation of infection control in registered tattooing premises in Victoria,
      1994.
AB  - Tattooists at a random sample of registered tattooing premises were surveyed for
      self-reported compliance with infection-control practices specified in the
      Victorian Standards of practice for tattooing, and some were observed while
      tattooing. Of 35 respondents, 94 per cent reported that they believed their
      practice fully met the standards, yet 19 per cent of tattooists did not have a
      copy of the standards at their premises. Most believed the standards could be
      improved. There was considerable discrepancy between reported practice and that
      observed. Few tattooists understood or implemented universal precautions, and
      while most wore gloves, there was low level of use of eye and clothing
      protection. Tattooists touched many surfaces that had not been cleaned or
      disinfected between clients. Ultrasonic cleaners were generally operated without
      lids. Because of this, they were a danger both to operators and their clients. At
      no premises was equipment used that had been both cleaned according to the
      standards and sterilised in an autoclave that had passed a sterilisation test.
      The situation in Victoria is similar to that identified in other states. There is
      an urgent need for training of tattooists and the environmental health officers
      who supervise them.

PMID- 9141725
TI  - The occurrence of cancer in a cohort of New South Wales coal miners.
AB  - To describe the incidence of cancer in coal miners in New South Wales (NSW)
      between 1973 and 1992, an inception cohort of all male coal industry employees
      who entered the industry between 1 January 1973 and 31 December 1992 was
      constructed from the medical examination records of the Joint Coal Board. This
      cohort was matched with the NSW State Cancer Registry to determine the occurrence
      and type of cancer. In the cohort of 23,630 men, 297 developed 301 primary
      cancers in the 20-year period of observation. The standardised incidence ratio
      (SIR) for all cancers was 0.82. Stomach cancer has been reported to be common in
      coal miners but the SIR for stomach cancer was not higher than average in this
      cohort. A cluster of non-Hodgkin's lymphoma has been reported in a NSW coal mine
      but an increased risk of this cancer was not evident in the industry as a whole.
      Similarly a cluster of cases of brain tumour has been reported. In this cohort,
      the SIR for brain tumour was 1.05 (95 per cent confidence interval (CI) 0.57 to
      1.76) and a risk for brain tumour remains unconfirmed. The SIR for malignant
      melanoma was 1.13 (CI 0.90 to 1.39) together and 2.02 (CI 1.31 to 2.98) for those
      workers who started in an open-cut mine. Overall, there does not appear to be a
      general risk of cancer in the NSW coal industry. Open-cut miners have an
      increased risk of malignant melanoma, which may be related to their exposure to
      the sun at work.

PMID- 9141726
TI  - Childhood pedestrian injuries: what can changes to the road environment achieve?
AB  - With the lack of any significant reduction in the mortality rates from pedestrian
      injury in Western Australia over the past decade, the need for efficacious
      prevention strategies is paramount. Using data from a case-control study of
      childhood pedestrian injuries, this study considered the effect on public health
      of an environmental initiative for prevention. Population-attributable risk
      proportions were calculated for the variables 'volume of traffic' and 'visual
      obstacles', which were found to predict the likelihood of pedestrian injury. The
      results suggest that 41 per cent (95 per cent confidence interval (CI) 13 to 62)
      of childhood pedestrian injuries can be attributed to volumes of traffic in
      excess of 10,000 vehicles per week, and 20 per cent (CI 11 to 48) of injuries can
      be attributed to visual obstacles on the street verge. It was also estimated that
      childhood pedestrian injuries could be reduced by up to 30 per cent if children's
      exposure to roads with volumes of traffic exceeding 10,000 vehicles per week,
      could be reduced to 15 per cent or less. Similarly, a reduction of up to 8 per
      cent could occur if visual obstacles on the roadside were reduced to 15 per cent.
      Changes to the road environment have potential to prevent injury to children.

PMID- 9141727
TI  - Teacher's questionnaire for vision problems: is it a help or a hindrance for
      school health screening?
AB  - The importance of early detection of vision problems in children is widely
      accepted. Screening by nurses in the first year of school is important in such
      early detection. The feasibility of using a questionnaire for teachers in place
      of the traditional screen was examined. In addition, the effect of prior in
      service training for teachers on the results of the questionnaire survey was
      assessed. The questionnaire had poor sensitivity and specificity. Used as the
      sole screen, it would have resulted in the unnecessary referral of healthy
      children, and more importantly, children with visual defects would have been
      missed. Further, there was no improvement in the outcome when prior in-service
      training on the questionnaire had been given. The questionnaire for teachers, as
      given, was an unsatisfactory alternative to the screening by health professionals
      and was not supported by this study.

PMID- 9141728
TI  - Service provision among adult public dental service patients: baseline data from
      the Commonwealth Dental Health Program..
AB  - Patients using publicly funded dental care have been reported to have frequent
      emergency visits and extractions; however, reports have been based on data from a
      limited number of sites around Australia. The aims of this study were to provide
      baseline data at the beginning of the Commonwealth Dental Health Program to
      describe the service characteristics of patients receiving publicly funded dental
      care, and to analyse factors associated with extraction of teeth. In
      collaboration with state and territory government health departments, data were
      collected on patient characteristics, visit details and services received by a
      cross-sectional sample of adult patients receiving dental care in Queensland in
      October 1993, in New South Wales, Victoria, South Australia, Tasmania, the
      Australian Capital Territory and the Northern Territory from March to April 1994,
      and in Western Australia in October 1994. Data were available for 17,653 dental
      visits (89.4 per cent were dentate, 56.6 per cent were female, 69.1 per cent were
      from capital cities, and 38.0 per cent visited for an emergency). For dentate
      persons, logistic regression showed that factors associated with extractions
      were: age (< 30 years odds ratio (OR) = 1.28, reference 30+ years), sex (male OR
      = 1.37, reference (female), indigenous persons (indigenous OR = 2.56, reference
      nonindigenous), visit type (emergency OR = 4.70, reference nonemergency), and
      location (noncapital OR = 1.29, reference capital city). In publicly funded
      dental care, retention of teeth might be enhanced through changes in visit
      patterns, particularly for younger, male, indigenous and rural patients. Improved
      access for care is needed to achieve more desirable visit patterns, which would
      include: less emergency care and more planned care, shorter waiting times for
      nonemergency care, and fewer extractions.

PMID- 9141729
TI  - Effects of group exercise on cognitive functioning and mood in older women.
AB  - A randomised controlled trial was conducted to determine whether a 12-month
      program of group exercise had beneficial effects on physiological and cognitive
      functioning and mood in 187 older community-dwelling women. The exercisers (n =
      94) and controls (n = 93) were well matched in terms of the test measures and a
      number of health and life-style assessments. The mean number of classes attended
      by the 71 exercise subjects who completed the program was 59.0 (range 26 to 82).
      At the end of the trial, the exercisers showed significant improvements in
      reaction time, strength, memory span and measures of wellbeing when compared with
      the controls. There was also an indication that anxiety had been reduced in the
      exercisers. Within the exercise group, improvements in memory span were
      associated with concomitant improvements in both reaction time and muscle
      strength. Also, within this group, initial mood measures were significantly
      inversely associated with improvements at retest, which suggests that the program
      may have normalised mood states in subjects who had high initial depression,
      anxiety and stress levels, rather than inducing improvements in all subjects.
      These findings suggest that group exercise has beneficial effects on
      physiological and cognitive functioning and wellbeing in older people.

PMID- 9141730
TI  - Demography of assault in a provincial Victorian population.
AB  - The study examined the frequency and patterns of assault within a large regional
      population of Victoria. The records of 860 victims of physical assault who
      presented to the Geelong Hospital emergency department during 1993 and 1994 were
      analysed retrospectively. The policy data on 1427 reported cases of physical
      assault, from the same catchment area and over a similar period of time, were
      also examined. The hospital data revealed that 65 per cent of assault victims
      were males aged from 15 to 34 years, that 58 per cent of presentations were
      within four hours of midnight, and 68 per cent were on Friday, Saturday or
      Sunday. Most assaults occurred on the streets, on footpaths, in open spaces or
      within dwellings, and the highest incidence was during the summer months. The
      police data showed similar patterns but from a different population of victims.
      It also showed an upward trend in the rates of assault in Victorian regional
      areas. The award-winning Geelong 'Local Industry Accord', a police and community
      intervention program, may have contributed to the decline in violence,
      particularly within the Geelong city centre, and has been suggested as a model
      for other community-based intervention programs. For intervention programs to be
      successful, the demography of assault within communities must be established and
      target groups identified. Hospital, police and victim surveys data do not
      identify accurately the population of assault victims. Improved methods of data
      collection and compatibility between databases already in existence may provide
      more accurate statistics upon which intervention programs may be based and their
      success evaluated.

PMID- 9141731
TI  - A profile of Australian family caregivers: diversity of roles and circumstances.
AB  - Research on family caregiving has been based largely on small samples, often
      drawn from support organisations or services, and has tended to focus on
      particular disability groups. Our study was population-based and included all
      ages and disabilities. As the first stage in a longitudinal research and health
      promotion program for informal caregivers, a statewide random survey of over
      26,000 households was conducted by telephone: 78 per cent of self-identified
      carers (N = 976) agreed to participate in a one-hour interview. This paper
      presents a sociodemographic profile of Australian caregivers. Four types of
      relationship between carers and care recipients (adult offspring, spouses,
      parents and other relatives and friends) provide the framework for results. Group
      differences were observed on most characteristics: for example, age, living
      arrangements, work status and duration of care. Care recipient characteristics,
      including difficult behaviours and need for assistance, are also reported, as
      well as use of and need for community services. What the findings reflected most
      was the heterogeneity of both caregivers and care recipients and the diversity of
      caregiving roles and circumstances.

PMID- 9141732
TI  - Effects and sustainability of a cervical screening program in remote Aboriginal
      Australia.
AB  - We assessed the effects of an organised cervical screening program, using a
      population-based cervical cytology register, for Aboriginal women in the Fitzroy
      Valley, a remote part of the Kimberley region of Western Australia. Comparison of
      age-specific screening rates in the area during 1987-88, 1990-92 and 1993-94
      showed that establishing the program in late 1989 was accompanied by dramatic
      increases in cervical screening rates, ranging from two- to over fourfold, with
      the largest increases in women aged 50 years and over. Following the departure of
      the coordinator in early 1993, screening rates decreased to between 76 per cent
      and 29 per cent of their 1990-92 levels, with the largest decreases occurring in
      the 40-49 and 60-69 years age groups. Rates were still above 1987-88 levels for
      most age groups. Of 545 women screened during 1991-92, 65 per cent had undergone
      a second Pap smear within the follow-up period of two to four years. Among women
      recommended for a repeat smear in two years, the probability of having a second
      smear was negatively associated with age (log-rank statistic = 35.58, 4 df, P <
      0.0001). Follow-up of smears recommended for repeat in 12 months or earlier was
      less adequate in 1993-94 (46 per cent) than in 1991-92 (75 per cent). The program
      was successful in recruiting a large proportion of eligible women within a
      relatively short time, but coverage, especially of older women, was not sustained
      after a decline in the functioning of the recall system owing to staffing and
      organisational changes.

PMID- 9141733
TI  - The use of tobacco, alcohol and other drugs by young Aboriginal people in Albany,
      Western Australia.
AB  - This paper describes patterns of tobacco, alcohol and other drug use among
      Aboriginal people aged 8 to 17 years in the town of Albany, Western Australia. Of
      a total of 110 young Aboriginal people residing in the town at the time of the
      study, 105 were interviewed by two trained Aboriginal research assistants using
      interview schedules that included questions based on the national guidelines for
      the comparability of studies of drug use among young people. The most commonly
      used drugs were tobacco, alcohol and cannabis. Use of other substances was
      usually experimental, The majority (57 per cent) of this population had not used
      any drugs, 13 per cent made some use of alcohol and/or tobacco, 15 percent were
      polydrug users, and 15 per cent were frequent polydrug users. Use of drugs
      increased with age: 48 per cent of those aged 15 to 17 were frequent polydrug
      users. Tobacco consumption was greater and alcohol use less than that reported
      among Western Australian secondary school children of comparable age.

PMID- 9141734
TI  - Aboriginal self-determination, education and health: towards a radical change in
      attitudes to education.
AB  - The establishment of community-controlled organisations as part of the Aboriginal
      self-determination movement in Australia has failed to deliver the expected
      social and health gains for the majority of indigenous people. Compared with that
      of indigenous people in New Zealand, The United States and Canada, Aboriginal
      health has shown little improvement over the past two decades. There is strong
      evidence to suggest that universal education is itself a tool for liberation and
      also that educational attainment translates directly into better health.
      Nevertheless, attempts to account for the continuing poor health of indigenous
      Australians has continued to overlook the role of education in explaining health
      status differentials. This is not an attempt to undervalue the significant
      achievements of the Aboriginal self-determination movement. Rather, it is an
      attempt to draw attention to lack of educational attainment as a contradiction in
      the indigenous struggle for self-determination and better health. Based on
      existing data, as well as personal observations and discussions, this preliminary
      investigation seeks to draw attention to the lack of formal education as a
      barrier to Aboriginal social and health improvement. Public health practitioners
      and policy makers are called on to consider working collaboratively with
      Aboriginal communities to ensure that formal education is not only popularised
      but also that governments are made accountable for their constitutional
      responsibilities towards Aboriginal education.

PMID- 9141735
TI  - Effect of gestational age misclassification on the pattern of low birthweight in
      Aborigines.
AB  - Are most births of Aboriginal babies with low birthweight preterm or full term?
      There is no consensus because of the difficulty in obtaining valid measurements
      of gestational age. In Queensland, between 1988 and 1992, there were 519 births
      of Aboriginal babies with low birthweight in excess of the number expected if
      aborigines had the same risk of low birthweight as whites. Most of these were
      preterm (males 76 per cent, females 65 per cent). Sensitivity analyses were used
      to investigate whether this result was robust to gestational age
      misclassification. Implausibly large misclassification proportions were required
      to make preterm low birthweight an insignificant contributor to the low
      birthweight excess in Aborigines. Therefore, efforts to reduce the number of
      preterm births should be given high priority. Unfortunately, significant
      reductions in the number of preterm births will not be achieved by reducing the
      prevalence of traditional risk factors for full-term low birthweight (for
      example, maternal smoking, teenage pregnancy). More work is needed to identify
      potentially modifiable risk factors for preterm birth.

PMID- 9141736
TI  - Towards guidelines for survey research in remote Aboriginal communities.
AB  - Based on our experience in developing and evaluating community-based health
      promotion programs in Aboriginal and Torres Strait Islander communities, we offer
      guidelines to assist nonindigenous health and public policy professionals whose
      information gathering in these communities includes the use of unstructured
      interviewing or survey questionnaires. The guidelines primarily apply to research
      among mainland remote Aboriginal communities, but are placed in a cultural
      context such that those dealing with Torres Strait Islanders and rural or urban
      community Aborigines also may benefit from the guidelines. The major aims of
      these guidelines are to facilitate communication between interviewers and
      indigenous interviewees and to ensure that interviewing is done with maximum
      sensitivity to cultural differences and with minimum discomfort to the
      respondents.

PMID- 9141737
TI  - Commentary: don't forget the plumber: research in remote Aboriginal communities.

PMID- 9141738
TI  - Differential effectiveness of telephone prompts by medical and nonmedical staff
      in increasing survey response rates: a randomised trial.
AB  - We conducted a randomised trial to determine the differential effectiveness of a
      telephone prompt by a medical researcher compared with a nonmedical research
      assistant in improving response rates of general practitioners to a survey and to
      compare personnel costs. A national random sample of Australian general
      practitioners was allocated randomly to two intervention groups. In advance of a
      self-administered questionnaire, Group A (n = 184) received a telephone prompt by
      a medical researcher and Group B (n = 189) a prompt by an experienced nonmedical
      research assistant. Other aspects of survey administration were identical for
      both groups. The five-month cumulative response rate obtained by the medical
      researcher (81 per cent) was not significantly different from that of 72 percent
      obtained by the research assistant (chi 2 = 3.3, 1 df, P = 0.07). For Group A,
      279 telephone calls, consuming 23 hours 15 minutes, were made. Group B required
      more calls (384) and more time (32 hours). Using the relevant award pay scales,
      the estimated personnel costs for each group were $631 and $601 respectively. We
      conclude that an experienced nonmedical research assistant is as effective as a
      medical practitioner in administering telephone prompts to enhance survey
      response rates, although savings are not necessarily made.

PMID- 9141739
TI  - Presentation of early otitis media in 'Top End' Aboriginal infants.
AB  - Otitis media is highly prevalent in Aboriginal Australians. This study found that
      otitis media was universal in 41 Aboriginal infants from the north of the
      Northern Territory, who were examined monthly from birth; more than one-third had
      experienced eardrum perforation. The earliest age at perforation was 44 days and
      the mean duration was 44.3 days. All subjects had acute otitis media or otitis
      media with effusion before perforation and after drum healing. This study,
      therefore, recommends that individual medical treatment should not be postponed
      until drum perforation occurs because otitis media develops first behind an
      intact drum and then may progress to perforation.

PMID- 9141740
TI  - Incidence and prevalence of hepatitis C among clients of a Brisbane methadone
      clinic: factors influencing hepatitis C serostatus.
AB  - The objective of this study was to describe the incidence and prevalence of
      hepatitis C infection among clients of a methadone program in Queensland. The
      clinical notes of clients receiving methadone for treatment of opiate dependence
      who first registered at the clinic after 1989 were perused for information about
      their serological status for hepatitis C and hepatitis B infections during a six
      week period in 1994. We followed hepatitis C negative clients until August
      September 1995. At study entry, 69 per cent of the clients were recorded as being
      hepatitis C positive. Of those who were negative, the seroconversion rate was 11
      per 100 person-years. The high incidence and prevalence of hepatitis C among
      methadone clients emphasises the need for effective early intervention strategies
      to prevent the transmission of hepatitis C among injecting drug users.

PMID- 9141741
TI  - Rooms for rent: injecting and harm reduction in Sydney.

PMID- 9141742
TI  - Antenatal care priorities.

PMID- 9141743
TI  - Attitudes of Sydney Chinese to voluntary euthanasia.

PMID- 9141744
TI  - Implementation of cystic fibrosis services in developing countries: memorandum
      from a Joint WHO/ICF(M)A meeting.
AB  - A Joint WHO/ICF(M)A meeting defined strategies for the implementation and
      development of cystic fibrosis (CF) services in countries where CF is thought to
      be more common than is appreciated by the medical profession or the public and
      where CF services are either non-existent or in the early stages of development.
      The following common problems in such countries were identified: underdiagnosis;
      reduced life expectancy (relative to developed countries) among those diagnosed;
      a clinical profile that may vary from the "classic" description; poor
      availability of necessary drugs; and a lack of CF services or basic research on
      the condition. The following recommendations were made concerning CF: neonatal
      screening projects should be set up to determine its incidence and identify
      affected infants; national and regional laboratories should be encouraged to
      identify the specific mutations responsible for the condition in their
      populations; centres for diagnosis and treatment should be developed, using a
      team approach; a national organization, involving families and friends of
      individuals with CF and other volunteers, should be established; a national
      registry should be set up; awareness about the condition should be improved and
      knowledge about it developed among medical professionals, public health
      authorities, and the general public; and increased collaboration between groups
      and organizations (including pharmaceutical companies) at the national, regional,
      and international levels should be developed in order to exchange information
      about and promote knowledge of CF, and to stimulate the development of CF
      services in developing countries.

PMID- 9141745
TI  - The development of MUAC-for-age reference data recommended by a WHO Expert
      Committee.
AB  - Low mid-upper-arm circumference (MUAC), determined on the basis of a fixed cut
      off value, has commonly been used as a proxy for low weight-for-height (wasting).
      The use of a fixed cut-off value was based on the observation that MUAC showed
      small age- and sex-specific differences. However, in 1993, a WHO Expert Committee
      concluded that age independence is not reflected in the true pattern of mid-upper
      arm growth, recommended the use of MUAC-for-age, and presented age- and sex
      specific MUAC reference data developed with observations obtained from a
      representative sample of children in the USA aged 6-59 months. In this article,
      we explain the methodology for the development of these data, present age- and
      sex-specific growth curves and tables and discuss the applications and
      limitations of MUAC as a nutritional indicator. To develop the reference data,
      estimates were first obtained for the mean and standard deviation of MUAC for
      each month of age using 7-month segmental regression equations; a 5th-degree and
      a 3rd-degree polynomial in age was then used to describe the mean and standard
      deviation, respectively, of MUAC-for age. These curves show important age
      specific differences, and significant sex-specific differences for boys and girls
      < 24 months of age. Correct interpretation of MUAC with regard to nutritional
      status requires the use of MUAC-for-age reference data such as those presented
      here.

PMID- 9141746
TI  - Rapid screening of marketed paracetamol tablets: use of thin-layer chromatography
      and a semiquantitative spot test.
AB  - Evaluated is the use of thin-layer chromatography (TLC) to determine the quality
      of paracetamol tablets marketed in Bangladesh. The procedure was carried out
      using a cheap and rapid TLC method developed by the U.S. Food and Drug
      Administration. Reported also is a semiquantitative specific spot test for
      screening paracetamol tablets. The results obtained indicate that, of the 38
      brands tested, three were spurious, while 11 were of borderline quality. In some
      cases, the results were also verified using the British Pharmacopoeia method. The
      simplified tests described in this article cannot replace the British
      Pharmacopoeia or U.S. Pharmacopoeia methods but can be employed as initial
      screening tests.

PMID- 9141747
TI  - Sustainability of pyrethroid-impregnated bednets for malaria control in Afghan
      communities.
AB  - Between 1992 and 1995 a series of studies was undertaken to assess the long-term
      suitability of pyrethroid-impregnated bednets (PIBs) for malaria control in
      Afghan refugee communities in two villages in North-West Frontier Province,
      Pakistan. During 1992, 86% of bednet owners volunteered to have their bednets re
      impregnated, and a further 15% of families purchased nets at two-thirds of cost
      price. From 1992 onwards, 27% of the villagers returned to Afghanistan, and
      annual house spraying campaigns were introduced to protect those still resident
      but sleeping without bednets. Within 3 years, these campaigns, together with
      PIBs, reduced the annual incidence of malaria by 87%, from 597 to 78 cases per
      1000 population. Nevertheless, 65% of resident families continued to re
      impregnate their nets annually with permethrin. To assess whether PIBs were still
      being used and were still protective, in view of these reduced transmission
      rates, we carried out a case--control study in 1994 on febrile or otherwise
      symptomatic patients presenting at village health centres. Comparison of the
      slide-positivity rates of PIB users and those without bednets showed that regular
      usage reduced the odds of contracting falciparum and vivax malaria to 0.22 (95%
      confidence interval (CI): 0.09-0.55) and 0.31 (95% CI: 0.19-0.51), respectively.
      There was no evidence of a sex- or age-bias in bednet use or in protective
      effect. The results indicate that a community-based PIB programme is an
      appropriate malaria control measure in areas where management or security
      problems make traditional house-spraying campaigns impossible. A relevant finding
      for those involved in the monitoring of bednet distribution projects is that the
      local coverage of bednets and the local impact on malaria, even when introduced
      to remote areas, can be estimated very cheaply by health centre microscopists who
      simply catalogue blood film diagnoses according to patients' bednet use
      practices.

PMID- 9141748
TI  - Urban-rural differences in the prevalence of coronary heart disease and its risk
      factors in Delhi.
AB  - A community-based epidemiological survey of coronary heart disease and its risk
      factors was carried out over the period 1984-87 on a random sample of adults aged
      25-64 years: 13,723 adults living in Delhi and 3375 in adjoining rural areas. ECG
      examination and analysis of fasting blood samples for lipids were performed on
      subjects with the disease and asymptomatic adults free of clinical
      manifestations. The overall prevalence of coronary heart disease among adults
      based on clinical and ECG criteria was estimated at 96.7 per 1000 and 27.1 per
      1000 in the urban and rural populations, respectively. Prevalences of a family
      history of coronary heart disease, hypertension, obesity and diabetes mellitus
      were significantly higher in the urban than in the rural population, and smoking
      was commoner among rural men and women. Mean levels of total serum cholesterol
      and low density lipoprotein cholesterol were higher among urban subjects; the
      mean level of triglycerides was higher in rural subjects. The proportions with
      total cholesterol levels > 190 mg/dl were 44.1% and 23.0% in urban and rural men,
      respectively, and 50.1% and 23.9% among urban and rural women, respectively. High
      density lipoprotein cholesterol levels < 35 mg/dl were found in 2.2% of urban men
      and 8.0% of rural men compared with 1.6% and 3.5% among urban and rural women,
      respectively. An abnormal ECG pattern (Q wave or ST-T changes) in asymptomatic
      individuals is also considered to be a risk factor for coronary heart disease. In
      asymptomatic adults, 1.7% of urban men and 1.2% of urban women showed abnormal Q
      waves compared with 0.3% of rural men and 0.4% of rural women. A higher
      proportion of asymptomatic women showed ST-T changes in both populations. Rural
      men and women had higher total calorie and saturated fat intakes than urban
      subjects. Differences in dietary cholesterol intake were marginal. Sodium intake
      was greater in urban adults. Average daily consumption of alcohol by urban men
      was 12.7 ml ethanol compared with 2.4 ml in rural men.

PMID- 9141749
TI  - Patients' associations and the control of leishmaniasis in Peru.
AB  - American mucocutaneous leishmaniasis is an important health problem in Peru,
      particularly in the mountainous Cuzco Region, where 25% of all new cases reported
      in 1989 were located. Cases have increased considerably since the beginning of
      the 1980s, when large-scale seasonal migration to endemic zones occurred,
      particularly the forest area of Madre de Dios, following the discovery of new
      gold deposits there, and the deterioration in the economic situation in Peru.
      Following the lack of official response from the Peruvian government, hundreds of
      people suffering from leishmaniasis in the Cuzco area formed self-help
      associations with the objective of obtaining the drugs needed to treat their
      disease. The major achievement of this spontaneous movement, which was supported
      by several public and private institutions, was to encourage sick people,
      particularly patients with mucosal lesions, to emerge from isolation. As a
      result, the prevalence and incidence of the disease have now considerably
      decreased in the region.

PMID- 9141750
TI  - A household survey of dysentery in Burundi: implications for the current pandemic
      in sub-Saharan Africa.
AB  - To characterize the epidemiology of dysentery (defined as bloody diarrhoea) in
      Burundi, we reviewed national surveillance data and conducted a household cluster
      survey including two case--control studies: one at the household, the other at
      the individual level. We estimated that community incidences for dysentery (per
      1000 residents) in Kibuye Sector were 15.3 and 27.3, and that dysentery accounted
      for 6% and 12% of all deaths, in 1991 and 1992, respectively. Factors associated
      (P < or = 0.05) with contracting dysentery were being female, using a cloth rag
      after defecation, a history of recent weight loss, and not washing hands before
      preparing food. The attributable risk, at the household level, of not washing
      hands before preparing food was 30%. Secondary household transmission accounted
      for at most 11% of dysentery cases. This study suggests that Shigella dysenteriae
      type 1 may be one of the leading causes of preventable mortality in Burundi and
      other African countries where effective antimicrobial agents are no longer
      affordable. Since hands were the most important mode of transmission of S.
      dysenteriae in this study, community-based interventions aimed at increasing hand
      washing with soap and water, particularly after defecation and before food
      preparation, may be effective for controlling dysentery epidemics caused by S.
      dysenteriae type 1 in Africa.

PMID- 9141751
TI  - Control of rubella and congenital rubella syndrome (CRS) in developing countries,
      Part 1: Burden of disease from CRS.
AB  - Congenital rubella syndrome (CRS) can lead to deafness, heart disease, and
      cataracts, and a variety of other permanent manifestations. In developing
      countries, the burden of CRS has been assessed as follows: by surveillance of
      CRS; by surveillance of acquired rubella; by age-stratified serosurveys; and by
      serosurveys documenting the rubella susceptibility of women of childbearing age.
      During rubella outbreaks, rates of CRS per 1000 live births were at least 1.7 in
      Israel, 1.7 in Jamaica, 0.7 in Oman, 2.2 in Panama, 1.5 in Singapore, 0.9 in Sri
      Lanka, and 0.6 in Trinidad and Tobago. These rates are similar to those reported
      from industrialized countries during the pre-vaccine era. Special studies of CRS
      have been reported from all WHO regions. Rubella surveillance data show that
      epidemics occur every 4-7 years, similar to the situation in Europe during the
      pre-vaccination era. In developing countries, the estimated average age at
      infection varies from 2-3 years to 8 years. For 45 developing countries we
      identified serosurveys of women of childbearing age that had enrolled > or = 100
      individuals. The proportion of women who remained susceptible to rubella (e.g.
      seronegative) was < 10% in 13 countries. 10-24% in 20 countries, and > or = 25%
      in 12 countries. Discussed are methods to improve the surveillance of rubella and
      CRS in developing countries.

PMID- 9141752
TI  - Control of rubella and congenital rubella syndrome (CRS) in developing countries,
      Part 2: Vaccination against rubella.
AB  - In 1995-96 we conducted a review of rubella immunization strategies. Worldwide,
      78 countries (more than one-third) reported a national policy of using rubella
      vaccine. This was closely related to country economic status. Based on the United
      Nations country classification, rubella vaccine is used in 92% of industrialized
      countries, 36% of those with economies-in-transition, and 28% of developing
      countries. Cases of congenital rubella syndrome (CRS) may be prevented as
      follows: by providing direct protection to women and/or schoolgirls (a selective
      vaccination strategy); by vaccinating boys and girls to provide indirect
      protection by reducing the transmission of rubella virus (a childhood vaccination
      strategy); or by a combination of these approaches (a combined strategy). A
      combined strategy was most commonly reported (60% of countries); seven countries
      (9%) reported a selective strategy; and 24 countries (31%) reported only
      childhood immunization. Experience has shown that it is essential to include
      vaccination of women of childbearing age in any rubella control strategy.
      Childhood vaccination alone may pose a risk of an increase in CRS cases. Although
      many countries have introduced rubella vaccine, few report any data on the impact
      of vaccination. Countries using rubella vaccine need to establish surveillance
      for rubella and CRS and monitor coverage in each of the target groups.

PMID- 9141754
TI  - Prevention of coronary heart disease in Sri Lanka.

PMID- 9141753
TI  - Factors affecting the immunogenicity and potency of tetanus toxoid: implications
      for the elimination of neonatal and non-neonatal tetanus as public health
      problems.
AB  - An estimated 400,000 deaths occur annually from neonatal tetanus (NT). In 1989
      WHO adopted the goal of eliminating NT as a public health problem worldwide. To
      achieve this, and to control non-neonatal tetanus (non-NT), WHO recommends that
      newborns be passively protected at birth by the antepartum administration of at
      least two doses of tetanus toxoid (TT) to their mothers and that all children
      subsequently receive at least three doses of diphtheria-tetanus-pertussis (DTP)
      vaccine. For this strategy to be effective, the TT used must be immunogenic.
      Potential factors that may affect TT immunogenicity need to be evaluated if NT is
      to be eliminated and if non-NT is to be controlled. Although data are
      conflicting, concurrent malarial infection may decrease the immune response to
      TT; however, malarial chemoprophylaxis may enhance the immune response.
      Malnutrition does not appear to affect immunogenicity; nevertheless, one study
      suggests that vitamin A deficiency is associated with an impaired immune
      response. Although it has been postulated that placental transfer of tetanus
      antibody is impaired in African women, a survey of the published literature
      suggests that this is not the case. Freezing TT has been shown to decrease its
      potency, but its impact on immunogenicity needs more evaluation.

PMID- 9141755
TI  - Experience with flexible fibreoptic bronchoscopy.
AB  - OBJECTIVE: To evaluate the usefulness of fibreoptic bronchoscopy as an
      investigation in respiratory medicine in Sri Lanka. DESIGN: 823 patients with
      chest opacities subjected to fibreoptic bronchoscopy. SETTING: General Hospital,
      Colombo. RESULTS: A definite diagnosis was made in 212 patients (25.7%).
      Bronchial carcinoma was diagnosed in 162 and pulmonary tuberculosis in 39
      patients. Pulmonary metastases, vocal cord carcinoma, tracheal stenosis,
      carcinoid tumour, Pneumocystis carinii, malignant thymoma with bronchial
      secondaries, polyps in the trachea and post-operative collapse of lung were the
      other diagnoses. CONCLUSION: It is a safe procedure in a Sri Lankan setting to
      diagnose bronchial carcinoma, unsuspected cases of pulmonary tuberculosis and
      other tracheo-bronchial lesions. It has definite advantages over rigid
      bronchoscopy.

PMID- 9141756
TI  - Iron absorption from a traditional Sri Lankan weaning food and the enhancing
      effect of ascorbic acid in adult male volunteers.
AB  - OBJECTIVE: To study absorption of iron from Centella gruel and the enhancing
      effect of ascorbic acid in young adult males. DESIGN: An in vivo absorption
      study. SETTING: Faculty of Medicine, Galle. METHODS: The percentage of iron
      absorbed from the Centella gruel was measured using a double isotope technique
      with 55Fe and 59Fe on 10 healthy male volunteers. OUTCOME MEASURE: Percentage of
      iron absorption from the gruel with and without ascorbic acid. RESULTS: The mean
      iron absorption from each meal of Centella gruel was 2.2% (SEM 0.8). This
      increased to 5% (SEM 1.6) by addition of 50 mg ascorbic acid. When ingested with
      ascorbic acid, the bioavailable nutrient density (BND) of the weaning food was
      increased from 0.23 to 0.53 mg iron/1,000 kcal. To satisfy the daily
      physiological requirements of iron in infants and toddlers, it was calculated
      that apart from ascorbic acid supplementation, the total iron content also needs
      to be increased from 2.05 mg to 4.0 mg/meal. CONCLUSION: Centella gruel cannot
      provide the amount of iron to meet the BND for iron required by infants and
      toddlers, unless supplemented with an enhancer of iron absorption such as
      ascorbic acid and its total iron content is increased.

PMID- 9141757
TI  - Fetal hydronephrosis, a one year follow up.
AB  - OBJECTIVE: To determine the underlying urological anomalies and the outcome
      during the first year, in babies with antenatally diagnosed hydronephrosis.
      DESIGN: A prospective descriptive study. SETTING: Southlands and Worthing
      Hospitals, Worthing, UK. METHOD: From January 1991 to December 1992, in the
      Worthing District Health Region, UK all babies with hydronephrosis persisting
      postnatally (69) were prospectively assessed for renal growth and function,
      general well-being, and complications if any. The diagnoses, treatment and
      complications occurring during the first year were analysed. RESULTS: Of the 69
      babies 4 were lost to follow up. The 65 fetuses assessed had the following
      underlying causes: transient in utero hydronephrosis 34 (52.3%), idiopathic
      hydronephrosis 9 (13.8%), isolated vesico-ureteric reflux 5 (7.6%), vesico
      ureteric reflux with other urological abnormalities 2 (3.1%), pelvi-ureteric
      junction obstruction 2 (3.1%), equivocal pelvi-ureteric junction
      obstruction/idiopathic hydronephrosis 4 (6.2%), multicystic dysplastic kidney 4
      (6.2%), polycystic kidneys 1 (1.5%) and patulous extrarenal pelvis 4 (6.2%).
      During one year of follow up 4 (6%) of babies needed surgical intervention and
      further 6 (9%) needed antibiotic prophylaxis. CONCLUSION: The majority of fetal
      hydronephroses is were self-limiting or benign. Vesico-ureteric reflux was the
      commonest urological abnormality. 23 (33%) apparently normal neonates detected on
      prenatal screening needed aggressive management or close monitoring.

PMID- 9141758
TI  - Comparison of minimum inhibitory concentrations to methicillin in heterogeneous
      and homogeneous methicillin resistant Staphylococcus aureus.
AB  - OBJECTIVE: To determine the minimum inhibitory concentration (MIC) to methicillin
      and compare it with the type of methicillin resistance in methicillin resistant
      Staphylococcus aureus (MRSA) isolated from clinical samples, and to evaluate the
      usefulness of beta-lactamase resistant penicillins such as cloxacillin for
      treatment of minor MRSA infections. DESIGN: Sixty-five strains of MRSA isolated
      from clinical samples were studied. Homogeneous and heterogeneous resistance to
      methicillin of these strains was determined by an efficiency of plating
      technique. The MICs to methicillin of all homogeneously resistant strains and an
      equal number of heterogeneously resistant strains were determined by the 'E'
      test. SETTING: General Hospital, Colombo; De Soysa Maternity Hospital for Women;
      Lady Ridgeway Hospital for Children. RESULTS: 171 strains of S aureus were
      isolated from specimens processed in the laboratory of the Department of
      Microbiology, Faculty of Medicine Colombo, during a 14-month period. Seventy
      (40.9%) were methicillin resistant. Fifty-three MRSA strains (81.5%) were
      heterogeneously resistant to methicillin. Only 12 of 65 strains were
      homogeneously resistant. Nine of 12 of the homogeneously resistant strains were
      from surgical wards. MICs for methicillin in the two groups were compared. Six of
      12 (50%) homogeneously resistant strains had very high levels of resistance to
      methicillin (MIC > 200 micrograms/ml). In contrast the MICs of all the
      heterogeneously resistant strains ranged from 16 micrograms/ml to 96
      micrograms/ml. CONCLUSIONS: The majority of clinical isolates of MRSA from
      hospitals in Colombo, Sri Lanka were heterogeneously resistant to methicillin
      with lower MICs for methicillin than the homogeneously resistant strains. Thus,
      beta-lactamase resistance penicillins such as cloxacillin may have a place in the
      treatment of minor MRSA infections. Surveillance studies to determine if there is
      an increase of homogeneously methicillin resistant MRSA are required.

PMID- 9141759
TI  - Assessment of client satisfaction in a paediatric ward.
AB  - OBJECTIVE: To assess client satisfaction of bystanders regarding (a) outcome of
      the illness and treatment and (b) advice given regarding the illness and
      attitudes of doctors. DESIGN: A descriptive cross-sectional study based on an
      interviewer administered questionnaire. SETTING: A ward at Lady Ridgeway
      Children's Hospital, Colombo. STUDY SAMPLE: The bystanders of children discharged
      in the morning during the defined study period of May to November 1994. RESULTS:
      The majority of bystanders were satisfied with the care of their children, but
      were less satisfied with the advice they had received regarding the illness.

PMID- 9141760
TI  - Home accidents in Sri Lanka--multicentre study.
AB  - OBJECTIVE: To determine the pattern of home accidents treated in four types of
      clinical practice. SETTING: A general practice and four hospital-based practices
      in accident service, general surgery and paediatric surgery. MATERIALS: Data were
      collected on a pre-tested questionnaire from 2672 patients who comprised all the
      home accident patients treated at the 5 centres during a 12 month period.
      RESULTS: Questionnaire was analysed and results presented in regard to several
      variables including age, size of household and peak period, location and type of
      accident. CONCLUSION: The characteristics of the victim, agent, environment,
      circumstances, cause and time of accident as determined by this study may be
      useful to formulate a prevention program.

PMID- 9141761
TI  - The right to die.

PMID- 9141762
TI  - Unresolving pneumonia in a child? Look for an aspirated foreign body.

PMID- 9141763
TI  - Successful surgery after ventricular septal rupture complicating acute myocardial
      infarction.

PMID- 9141764
TI  - Practical aspects of aerosol therapy in asthma (1)

PMID- 9141765
TI  - The feasibility of day case surgery for dilatation and curettage procedures in
      Sri Lanka.

PMID- 9141766
TI  - Use of aspirin in ischaemic heart disease.

PMID- 9141767
TI  - An unusual case of haemorrhagic cystitis.

PMID- 9141768
TI  - Multi-drug resistant malaria in Sri Lanka.

PMID- 9141769
TI  - No-suicide contracts and no-suicide decisions.

PMID- 9141770
TI  - Is psychotherapy helpful for adolescent suicide attempters?

PMID- 9141771
TI  - Suicide in a general hospital: the case of the elderly.

PMID- 9141772
TI  - Letters across the Pacific.

PMID- 9141773
TI  - State standards and suicide prevention: a lone star.

PMID- 9141774
TI  - Preventing teenage suicide in New York.

PMID- 9141775
TI  - Contracting for safety: a concept analysis.
AB  - The concept of contracting for safety, although a popularly accepted method for
      managing suicidal patients, has no scientific evidence to support its
      effectiveness. There are questions regarding the clinical justification. This
      article provides a concept analysis of contracting for safety to evolve and
      clarify exemplary criteria of the concept within psychiatric nursing practice. At
      times in clinical practice, contracting is often the primary factor in clinical
      decision-making, justifying a lower level of intervention. If a patient is
      inebriated or psychotic, he or she cannot enter into a legal contract. There may
      be undue reliance on the patient's apparent willingness to contract for safety.
      There may be little opportunity to establish a therapeutic relationship with the
      concomitant rapport and trust necessary for contracting. If it is used at all,
      contracting for safety should be used judiciously.

PMID- 9141776
TI  - Suicidal behaviors in homosexual and bisexual males.
AB  - A stratified random sample of 750 males in Calgary, Canada, aged 18-27 years,
      were given questions on sexual activity and orientation. Mental health questions
      included a measure of suicidality and of acts of deliberate self-harm. A
      computerized response format, which has been established as a good method for
      eliciting sensitive personal data, ensured anonymity. Almost 13% of the males
      were classified as homosexual or bisexual on the basis of being currently
      homosexually active or by self-identification. Significantly higher rates of
      previous suicidal ideas and actions were reported by homosexually oriented males
      than by heterosexual males. Homosexually oriented males accounted for 62.5% of
      suicide attempters. These findings, which indicate that homosexual and bisexual
      males are 13.9 times more at risk for a serious suicide attempt, are consonant
      with previous findings. The predominant reason for the suicidality of these young
      males may be linked to the process of "coming out," especially for those who
      currently have high levels of depression. These results underscore the need for
      qualified services rarely available to homosexually oriented youth.

PMID- 9141777
TI  - Suicide-related crimes in contemporary European criminal laws.
AB  - This article describes suicide-related penal legislation in contemporary Europe,
      and analyzes and relates the results to cultural attitudes towards suicide and to
      national suicide rates. Data were obtained from 42 legal entities. Of these, 34
      have penal regulations which--according to definition--chiefly and directly deal
      with suicide. There are three main types of act: aiding suicide, abetting
      suicide, and driving to suicide. The laws vary considerably with regard to which
      acts are sanctioned, how severely they are punished, and whether any special
      circumstances such as the motive, the result, or the object can make the crime
      more serious. Various ideologies have inspired legislation: religions, the
      euthanasia movement, and suicide prevention have all left their mark. There are
      some cases in which neighboring legal systems have clearly influenced laws on the
      topic. However, the process seems mostly to have been a national affair,
      resulting in surprisingly large discrepancies between European legal systems. The
      laws seem to reflect public opinions: countries which punish the crimes harder
      have significantly less permissive cultural attitudes towards suicide. Likewise,
      suicide rates were significantly higher in countries with a narrow scope of
      criminalization and milder punishments for suicide-related crimes. The cultural
      and normative elements of society are connected with its suicide mortality.

PMID- 9141779
TI  - "Professional" testimony.

PMID- 9141778
TI  - The effect of suicide prevention centers on suicide in Japan.

PMID- 9141780
TI  - Evaluating mullerian anomalies as a cause of recurrent pregnancy loss.

PMID- 9141781
TI  - Summary of the NIH Consensus on Cervical Cancer. National Institutes of Health
      Office of Medical Applications of Research.

PMID- 9141782
TI  - Threat to medicine's most successful cancer screening test. College of American
      Pathologists.

PMID- 9141783
TI  - Physician responsibility.

PMID- 9141784
TI  - Is health care a right.

PMID- 9141785
TI  - Attitudes towards alcohol use among Bulgarians-Christians and Turks-Muslims.
AB  - The attitude towards drinking in a given culture plays a very important role in
      the use and abuse of alcoholic beverages. The purpose of our study was to examine
      and compare this attitude among the Bulgarians-Christians and Turks-Muslims in
      Bulgaria. The sample comprised 618 subjects--316 Bulgarians-Christians and 302
      Turks-Muslims, selected by means of a randomized cluster design. The sample was
      stratified by ethnic identity, gender, age and place of residence (town vs.
      village). This methodology provided us with a way of controlling these
      confounding variables. The survey was conducted with a standardized questionnaire
      designed specifically for the study. The findings show that a greater percentage
      of Turks-Muslim than of Bulgarians-Christians (including those respondents who
      regularly use alcohol) are in favour of an official prohibition of alcohol in
      society and even moderate use on special occasions is inadmissible to them.
      Women, rural residents, people with lower educational status, senior citizens and
      those to whom religion plays an important part in their lives predominate in the
      social structure of the Turkish sub-sample favouring official prohibition. Their
      cultural readiness to say "No" to alcohol is viewed in the context of the
      abstinent Islamic culture.

PMID- 9141787
TI  - Clinical characteristics of women with endometriosis.
AB  - The author followed prospectively the clinical presentation of endometriosis in
      413 patients with subsequently confirmed endometriosis in 1994 laparotomies
      performed between 1984 and 1988. Age at menarche and at the time of clinical
      presentation of the disease, menstrual cycle abnormalities and the rest of the
      symptoms and signs of the condition, together with the findings on examination
      are presented. The correlations between the signs and symptoms and the clinical
      characteristics are presented by the author expand the previously published
      reports in the literature.

PMID- 9141786
TI  - Postnatal follow-up of the oxygenation index, arterial to alveolar oxygen tension
      ratio and alveolar arterial oxygen tension difference values in neonates with the
      respiratory distress syndrome treated with conventional ventilatory support.
AB  - Recent development of sophisticated intensive care technique for use in newborn
      infants with the respiratory distress syndrome (RDS) has resulted in changes in
      the therapeutic strategies and moved the problem of neonatal survival into the
      realm of new therapeutic realities. At present, the mechanical ventilation
      methods form an integral part of the intensive care strategy of infants with RDS.
      They have come to the forefront of infant care because of their successful use in
      ventilatory support and children survival where other therapeutic modalities have
      failed. The present prospective observational longitudinal study was designed to
      assess the real-time convenience, reliability and accuracy of the changes in the
      oxygenation index (OI), arterial-to-alveolar oxygen tension ratio (a/A PO2) and
      alveolar-arterial oxygen gradient (A-a)DO2 in ventilator-dependent neonates with
      RDS, to analyze their feasibility and potential information yield in oxygen
      inhalation therapy as well as their prognostic implications and predictive value.
      Twenty neonates with RDS, heralded by respiratory failure which necessitated the
      initiation of oxygen inhalation therapy and ventilatory support within 24 hours
      of birth, were enrolled in the study. Ten of the infants survived and the
      remaining ten died. OI, (a/A PO2) and (A-a)DO2 were followed up sequentially and
      thoroughly analyzed as the primary outcome measures of the study. The indices
      were calculated on the basis of the complete monitoring of the ventilatory
      equipment parameters and acid-base status carried out on an hourly basis. Our
      results show that: 1. The combination of three indexes (OI, (a/A)PO2 and (A-a)DO2
      we propose is a useful discriminating predictor of neonatal lung maturity
      reflecting arterial blood gas status in ventilator-dependent neonates with RDS.
      2. The indices detect the efficacy of the modern conventional ventilatory support
      with real-time convenience and reliable accuracy forming the cornerstone of
      clinical decision-making in RDS neonatal intensive care and allowing timely
      corrections of the ventilatory equipment parameters. 3. The prospective follow-up
      of these indices improves the predictive value as compared to any single test of
      neonatal lung maturity and has important prognostic implications in the
      management of neonates with RDS.

PMID- 9141788
TI  - Cyclic adenosine monophosphate (cAMP) levels in predialysis patients with chronic
      renal failure.
AB  - We studied the changes in the urinary cAMP level in fifty-five predialysis
      patients (30 men and 25 women) with chronic renal failure (CRF). The excretion of
      cAMP in 20 patients with first-degree CRF (serum creatinine levels below 356.6
      mmol/I) and 15 patients with second or third degree CRF (serum creatinine below
      800 mmol/I) was compared with that of 20 age-matched controls using the original
      I-125 RIA (radioimmunoassay) kit of Incstar Corporation, USA. The urinary cAMP
      was within normal limits in first-degree CRF patients (mean +/- Sx = 2,617 +/-
      268.2 nmol/l) whose serum calcium level was slightly decreased. When calculated
      per 100 ml of glomerular filtration rate, their urinary cAMP level was
      significantly elevated--101.17 +/- 0.39--as compared with that of the controls-
      2.5 +/- 0.2. The urinary cAMP excretion was significantly higher in second and
      third degree CRF patients--mean 3,755 +/- 435.2 nmol/l, p < 0.05. This increase
      correlated with hypocalcemia whereas the serum alkaline phosphatase levels
      remained normal. 20% of the patients with second or third degree CRF had normal
      urinary cAMP excretion. In our opinion, urinary cAMP levels can reliably be
      employed as a sensitive and specific indicator of the onset of mild secondary
      hyperparathyroidism in predialysis patients with CRF.

PMID- 9141789
TI  - Evaluation of an ion-selective electrolyte analyzer: Microlyte 6.
AB  - Microlyte 6 (Kone, Finland) is an ion-selective analyzer designed to measure
      simultaneously the concentration of six important electrolyte parameters-
      potassium, sodium, chloride, ionized calcium, ionized magnesium and pH in whole
      blood, serum and plasma. Two values are obtained in analyzing the ionized
      fractions of magnesium and calcium--one at the actual pH and another at a
      recalculated measurement for pH = 7.4. Direct determination of ionized calcium
      and ionized magnesium simultaneously with that of the other electrolytes is of
      great clinical significance. It is only recently that ion-selective analysis of
      ionized magnesium has been proposed. The analytical reliability of the results
      and the operational characteristics of the Microlyte 6 ion-selective analyzer
      were evaluated for approximately one year. The coefficient of variation of the
      results in the reference and pathological range was 0.49%-2.23%, and 0.68%-4.42%
      for the within-run and between-run series, respectively. The inaccuracy of the
      results expressed by d% was from -4.23% to +4.06%. The comparative evaluation of
      the results for potassium, sodium, chloride, and ionized calcium between
      Microlyte-6 and the clinical chemistry analyzer Dynamic (Kone) showed a high
      correlation (correlation coefficient in the range 0.9868-0.9970). The correlation
      between the results for the ionized fraction and those obtained for total
      magnesium was consistent with that generally given in the literature.

PMID- 9141790
TI  - Application of soluble dietary fibres in treatment of hyperlipoproteinemias.
AB  - Soluble dietary fibres as ingredients of our meal play an important role in both
      the prevention and treatment of hyperlipoproteinemias. We studied the effect of
      highly esterified sorbitol-granulated apple pectin on lipid metabolism in
      patients with hyperlipoproteinemia. They were all female (aged 40 to 60 years)-24
      with type IIa and 23 with type IIb hyperlipoproteinemia. The levels of the total
      plasma cholesterol, the cholesterol in low- and high-density lipoproteins, plasma
      triglycerides, as well as the lipidogram in these patients were dynamically
      monitored for three months. Favourable changes of the basic parameters of lipid
      metabolism were the most essential being the changes in the plasma cholesterol in
      the first six weeks (P < 0.001). This parameter can adequately be used as a
      working criterion in controlling the therapeutic effect of pectin in
      hyperlipoproteinemias types IIa and IIb.

PMID- 9141791
TI  - Our experience in minimized surgery for retinal detachment: first results.
AB  - This study included the first 35 patients with retinal detachment that underwent
      cryopexy and scleral segmental buckling by silicone sponge with nondrainage and
      without serclage after Lincoff. Precise localization of the retinal lesions and
      proper circumferential cryopexy was achieved intraoperatively under the guidance
      of indirect ophthalmoscope provided with +20/+30d biaspherical lens (Volk, USA).
      Mean age of the patients was 42 +/- 11 years. A single hole/break was visualized
      in 20%, two holes/breaks in 26%, and more than two holes/breaks in 40% of the
      patients; disinsertion of the retina of one quadrant was present in 14%. The
      duration of the disease was less than 3 months in 66% and more than 3 months in
      34% of the patients. On the first postoperative day anatomical reattachment of
      the retina was achieved in 86% of the patients and in 14% of the resorption was
      delayed until day 7. Postoperative haemophthalmus, vitreitis, ischaemia of the
      anterior ocular segment, or elevated intraocular pressure were found in none of
      the patients. All patients were discharged with reattached retinas. Visual acuity
      was more than 0.5 in 60% and from 0.1 to 0.5 in 40% of the patients. At the last
      postoperative examination the visual acuity was 1.0 in 40%, 0.5-0.9 in 40% and
      0.1-0.4 in 20% of the eyes. The retina was reattached in all patients. The method
      of minimized surgery for retinal detachment yields good anatomical and functional
      results. It helps to avoid the postoperative complications of conventional
      scleroplastic surgery with serclage and drainage.

PMID- 9141792
TI  - Application of the a priori methods for genetico-mathematical analysis of the
      inheritance pattern of ulcer disease.
AB  - The a priori methods were used to perform a detailed genetico-mathematical
      analysis of the pattern ulcer disease is inherited. The study included families
      of 351 probands. Of these, 267 were with duodenal ulcer, 57 with gastric ulcer
      type II, and 27 with gastric ulcer type III. The types of gastric ulcer were
      defined according to the classification proposed by H. Johnson. The cases of
      duodenal ulcer were also analyzed depending on the type of familial
      predisposition of the patients. The results from Bernstein's a priori method and
      Li's a priori correction method exclude autosomal recessive pattern of
      inheritance of the three types of peptic ulcer, not even in the families with
      healthy but hereditarily predisposed parents. On the other hand, the difference
      between the numbers of actually observed and theoretically predicted sick
      children in all groups studied, including those in the families with one sick
      parent, found by applying the Hogben modification of Bernstein's a priori method,
      is not consistent with an autosomal dominant pattern of inheritance. Nor is this
      inheritance pattern consistent with the finding that there are no essential
      differences between the quantitative parameters of the families with one or two
      sick parents. It is, therefore, concluded that this disease is not possible to be
      passed down in generations in a monogenic mode.

PMID- 9141793
TI  - Treatment of hemorrhagic periodontitis using neopredin.
AB  - Thirty hemorrhagic periodontitis adult patients completed a 90-day controlled
      clinical study to determine the clinical effects of the antiinflammatory
      preparation neopredin gel containing prednisolone, neomycin sulfate and
      chlorhexidine when used an adjunct to scaling and root planing. The results were
      evaluated using the Quigley-Hein plaque index, the Schour-Massler gingival
      bleeding index, the Svrakov-Pissarev gingival vital staining index, the Muleman
      Son sulcus bleeding index and the percentage of bleeding on probing sites.
      Treatment with neopredin resulted in consistently lower values of the mean plaque
      index score, the gingival bleeding index score, the vital staining index score
      and the sulcus bleeding index score at days 14.30 and 90. A significant reduction
      in the mean pocket probing depth was observed at day 30. The first symptoms of
      recurrent gingival inflammation were noticed at day 90. Our results indicate that
      neopredin is effective in reducing supragingival plaque accumulation, gingival
      inflammation, bleeding on probing and periodontal pocket depth and these
      reductions are highly significant.

PMID- 9141794
TI  - Comparative genetico-mathematic analysis of essential hypertension and coronary
      heart disease mode of inheritance: a study using direct methods testing.
AB  - Essential hypertension (EH) and coronary heart disease (CHD) very often exhibit
      familial recurrence pattern, which are estimated in the Bulgarian population at
      63.11% for EH and at 48.90% for CHD. The author made comparative genetico
      mathematical analysis of the inheritance patterns of the two diseases. Examining
      the pedigrees from a large number of families two data sets were formed and
      analyzed separately: a subgroup of families of probands with phenotypically
      unaffected parents, in which the genealogical pattern was most often consistent
      with a recessive model of inheritance and a subgroup of families of probands with
      one or both parents affected, in which the pedigree analysis resembled that of a
      disease with a monogenic dominant model of inheritance. The segregation
      coefficients obtained in the subgroup of families with two healthy parents most
      often varied from 0.298 to 0.362--results that consistently reject the hypothesis
      of recessive inheritance; the respective coefficients obtained by the same direct
      methods in the subgroup of families with one or both parents affected showed
      values from 0.279 to 0.468--findings rejecting the hypothesis of dominant model
      of inheritance. The author pointed out the identical relationships exhibited by
      genetico-mathematical testing of EH and CHD, a fact demonstrating the significant
      genetic proximity between the two diseases. Conclusions are made about the
      complex and specific relationships between genetic and environmental risk factors
      in the two diseases.

PMID- 9141795
TI  - Sociobiological factors and physical development of newborn infants in Plovdiv.
AB  - On the basis of data from a study, conducted in 1995 in Plovdiv, the correlation
      between newborn infants' physical development characteristics and some biological
      and social factors (maternal age, number of pregnancies, birth order, social
      class and educational level) was analyzed. Four basic anthropometric indices-
      height, body weight, head and chest circumferences were examined. The
      anthropometric indices of newborn infants in Plovdiv are the highest in second or
      third pregnancies. Birth order exerts significant influence on the physical
      development of newborn infants--the highest values are recorded at the second
      birth. The anthropometric indices are clearly dependent on mother's age. They
      increase with maternal age and reach their maximum in age group 30-34 years. The
      anthropometric indices values equalized in newborn infants from mothers--white
      and blue collar workers, while the values are significantly lower in newborns of
      unemployed mothers. Newborn infants' physical development of mothers with primary
      and high-school education is significantly inferior compared to children of
      mothers with higher educational levels.

PMID- 9141796
TI  - Accelerative changes in some anthropometric indices of newborn infants in Plovdiv
      during the period from 1939 to 1995.
AB  - Periodical observation and comparison of newborn infants' physical development
      indices gives an idea of the dynamics of accelerative changes and the efficacy of
      implemented health and social programs for maternity protection in a given
      country. The author performs a longitudinal study of the basic anthropometric-
      birth height and weight of newborn infants in Plovdiv for a 56 year period. Two
      periods are outlined. The first one, 46 years long, is characterized with a
      marked increase of the anthropometric values and lasts till 1975. After that the
      acceleration rate levels off and gradually slows down. In the second 10 year
      period an abrupt decrease of newborn infants' birth height and weight is
      recorded, as their values drop to the levels obtained in the 1946/47 study. The
      author relates this negative trend to the economic crisis in the country, the
      progressive impoverishment of the population, the unemployment and insecurity in
      the future. The existing social and health facilities for maternity protection in
      the country are estimated as inadequate for the present situation.

PMID- 9141797
TI  - Our experience in the diagnostics of liver and spleen hemangiomas.
AB  - We studied the potentials of conventional imaging methods (sonography, computed
      tomography) and invasive imaging methods (digital subtraction angiography, fine
      needle biopsy under sonographic guidance) in diagnosing liver and spleen
      hemangiomas. 384 patients underwent ultrasound investigation for suspected focal
      lesions of liver and spleen. Hemangioma was diagnosed in 83 patients. Computed
      tomography with contrast enhancement was performed on 62 of these 83 patients.
      The diagnosis of hemangioma was confirmed in 38 (61.3%) patients. In 22 patients
      the combination of sonography and computed tomography failed to provide
      indubitable diagnosis. Digital subtraction angiography was performed in 11 of
      them; the remaining 11 patients underwent fine needle biopsy under sonographic
      guidance. The authors achieve precision in the diagnosis of liver and spleen
      hemangiomas by employing combinations of above mentioned imaging methods.

PMID- 9141798
TI  - Adverse drug reaction monitoring in pediatric practice.

PMID- 9141799
TI  - Retinopathy of prematurity: incidence and risk factors.
AB  - OBJECTIVE: To determine the incidence of Retinopathy of Prematurity (ROP) in high
      risk babies admitted to the neonatal unit and to study risk factors for it's
      development. DESIGN: Prospective cohort study. SETTING: Level II Neonatal
      Intensive Care Unit. SUBJECTS: 100 babies admitted to the neonatal unit during a
      4 year period who were below 1500 g or whose gestation was < or = 34 weeks.
      METHODS: Examination of the eye was done in the neonatal unit or in the neonatal
      follow up clinic by an Ophthalmologist by indirect Ophthalmoscopy at 4-6 weeks
      postnatal age. RESULTS: The incidence of ROP was 46%. Of the 100 babies screened,
      21 had stage I, 14 had stage II, 8 had stage III and 3 had stages IV and V. The
      incidence of ROP was 73.3% among < 1000 g babies and 47.3% among < 1500 g babies.
      The incidence of ROP among 28-29 weeks, 30-31 weeks and 32-33 weeks babies was
      83%, 60% and 50%, respectively. The maximum stage of ROP developed between 37-42
      weeks post conceptional age in 69% subjects. On univariate analysis, gestation <
      or = 32 weeks, anemia, Blood transfusions, apnea and exposure to oxygen
      significantly increased the risk of developing ROP. On multivariate logistic
      regression analysis, anemia and duration of oxygen therapy were the significant
      independent predictors of development of ROP. Nine of the 46 babies underwent
      cryotherapy for threshold ROP. CONCLUSION: The incidence of ROP among high risk
      babies is significant and duration of oxygen therapy and anemia are independent
      factors predicting the development of ROP. All high risk babies should be
      screened for ROP. Cryotherapy is a relatively simple procedure which can be done
      in the neonatal unit.

PMID- 9141800
TI  - Hemostatic profile in nephrotic syndrome.
AB  - OBJECTIVE: To evaluate the coagulation profile and its relation to steroid
      therapy, and the frequency of thromboembolic complications and its correlation
      with coagulation parameters in nephrotic syndrome (NS). SETTING: Hospital based.
      SUBJECTS AND METHODS: Forty children with NS were subdivided into four groups,
      namely, fresh cases, steroid dependent, remission after therapy and steroid
      resistant. An equal number of age and sex matched children served as controls. In
      all the study and control subjects, detailed clinical examination, liver function
      tests, renal function tests and detailed coagulation profile were done.
      Evaluation of renal veins and inferior vena cava for the presence of thrombosis
      was also done by abdominal ultrasonography. RESULTS: Thrombocytosis was detected
      in 57.5% and the degree of thrombocytosis was directly related to the amount of
      proteinuria. The mean prothrombin and thrombin times were within normal range in
      the study children. The activated partial thromboplastine time (APTT) was
      prolonged in six cases (15%) and three out of these six children had
      thromboembolic complications. Antithrombin-III level was significantly lower (p <
      0.001) whereas protein C and S were significantly elevated (p < 0.001) as
      compared to controls. The levels became normal with remission of the disease.
      Steroid therapy significantly increased the levels of proteins C, protein S. AT
      III and fibrinogen as compared to controls. Thromboembolic complications were
      seen in 3 cases (7.6%) and were associated with very low levels of AT-III and
      protein C and all three had serum albumin below 2 g/dl. CONCLUSIONS: The
      importance of coagulation profile in nephrotic syndrome is highlighted and a high
      index of suspicion for thromboembolic complications is warranted in patients with
      thrombocytosis, hyper fibrinogenemia, prolonged APTT and in children with low
      levels of AT-III, protein C and protein S.

PMID- 9141801
TI  - Assessment of iodine deficiency disorders using the 30 cluster approach in the
      National Capital Territory of Delhi.
AB  - OBJECTIVE: Iodine Deficiency Disorders (IDD) are a major public health problem in
      India. The National Capital Territory (NCT) of Delhi is a known iodine deficiency
      endemic area. The Delhi Government banned the sale of non-iodised salt since
      1989. The present study was conducted to assess the status of IDD after 7 years
      of salt iodisation programme in the state. DESIGN: Cross sectional. METHODOLOGY:
      The recent indicators recommended by the World Health Organization-United Nations
      Childrens Fund-International Council for the Control of Iodine Deficiency
      Disorders (WHO-UNICEF-ICCIDD) were utilized for the assessment of IDD. A total of
      30 clusters were selected using population proportionate to size cluster sampling
      procedure. In each identified cluster, one primary school was selected using
      random sampling. A total of 6911 school children in the age group of 8-10 years
      were included for the study. RESULTS: The total goiter prevalence rate was 8.6%
      while 2.1, 8.4, 17.6 and 71.9% of the children had urinary iodine excretion
      levels of < 2, 2-4.9, 5-9.9 and 10 and above mcg/dl, respectively. The median
      urinary iodine excretion was 17 mcg/dl. Of the 1854 salt samples analyzed, salt
      with a nil iodine content was consumed only by 1.4% of the beneficiaries. Forty
      one per cent of families consumed salt with an iodine content of less than 15
      ppm. CONCLUSION: IDD continues to be a public-health problem in the NCT of Delhi.
      There is a need of strengthening the existing monitoring system for the quality
      of iodised salt.

PMID- 9141802
TI  - Immune thrombocytopenic purpura.

PMID- 9141803
TI  - HIV and breastfeeding.

PMID- 9141804
TI  - Sources of error in clinical research.

PMID- 9141805
TI  - Clinical efficacy of Cefuroxime axetil in S. typhi.

PMID- 9141806
TI  - Salmonella typhi meningitis in infants.

PMID- 9141808
TI  - Transcatheter embolisation of pulmonary arteriovenous fistula.

PMID- 9141807
TI  - Prevention of subclinical vitamin K deficiency based on PIVKA-II levels: oral
      versus intramuscular route.

PMID- 9141809
TI  - Recovery from pulmonary mucormycosis and candidiasis in diabetic ketoacidosis.

PMID- 9141810
TI  - Mesangial proliferative glomerulonephritis and nephrotic syndrome with hepatitis
      A virus infection.

PMID- 9141811
TI  - Acute-toxicity of vitamin A administered with measles vaccine.

PMID- 9141812
TI  - Comparative study of perinatal mortality and morbidity in the community and at
      Medical College Hospital, Patna.

PMID- 9141813
TI  - Safe bilirubin level for term babies with non-hemolytic jaundice.

PMID- 9141814
TI  - Comprehensive child care.

PMID- 9141815
TI  - Acyclovir in chickenpox.

PMID- 9141816
TI  - Care of adolescents.

PMID- 9141817
TI  - Potential toxicity of vitamin A supplementation in infancy.

PMID- 9141818
TI  - Chemotherapy for cerebral malaria.

PMID- 9141819
TI  - Solar radiation and human health.

PMID- 9141820
TI  - Wild poliomyelitis outbreak in Albania.

PMID- 9141821
TI  - Multivitamin supplementation in newborns.

PMID- 9141822
TI  - Traumatic pharyngeal pseudo diverticulum.

PMID- 9141823
TI  - Helicobacter pylori infection.

PMID- 9141824
TI  - Endoscopic, histologic and microbiologic evaluation of upper abdominal pain with
      special reference to Helicobacter pylori infection.
AB  - OBJECTIVE: To study children with significant upper abdominal pain of
      unidentifiable etiology and evaluate: (a) the relationship of pain to
      inflammatory esophago-gastro-duodenal lesions and Helicobacter pylori (HP)
      infection, and (b) the response to specific therapy. DESIGN: Prospective study.
      SETTING: Pediatric section of a tertiary referral gastroenterology center.
      SUBJECTS: Thirty three consecutive children with significant upper abdominal pain
      [mean age 9.9 +/- 2.7, range 4-15 years; 20 males] were subjected to upper
      gastrointestinal tract endoscopy and antral mucosal biopsies obtained for rapid
      urease test (RUT), Gram's staining of impression/crush smears and culture for HP
      and histologic examination. Patients with HP gastritis were treated with triple
      therapy, colloidal bismuth subcitrate, amoxycillin and metronidazole, for two
      weeks. At 8 weeks from the initiation of therapy, patients were re-evaluated for
      symptoms and HP eradication by repeat endoscopy and antral biopsies. Patients
      with esophagitis, gastritis and duodenitis without HP infection were treated with
      ranitidine for 6 weeks. All the patients were followed up for 6 months. RESULTS:
      Histology revealed antral gastritis in 28/33 (85%) patients. HP infection was
      present in 12/28 (43%) patients with antral gastritis. Symptomatic improvement
      with triple therapy was observed in 10/12 (83%) patients with HP gastritis and
      eradication of HP in 5/7. Improvement on ranitidine therapy was observed in 12/16
      (75%) patients with HP negative gastritis. On follow-up, no patient with initial
      improvement with therapy had relapse of symptoms. CONCLUSION: Symptomatic
      children with HP related gastritis should be treated with triple therapy and HP
      negative gastritis with H2-receptor antagonist.

PMID- 9141826
TI  - Isolation of poliovirus from cases of acute flaccid paralysis.
AB  - OBJECTIVE: To evaluate the frequency of isolation of polio and other viruses from
      fecal samples in subjects with acute flaccid paralysis in northern parts of
      India. SETTING: Rural and Urban Immunization Centers used for Expanded Programme
      on Immunization. METHODS: 219 fecal samples were collected by anal tube in 1992
      from Punjab, Haryana, Himachal Pradesh and Chandigarh and processed for virus
      isolation. RESULTS: Of 219 fecal samples, 103 (47%) were positive for viruses in
      the age group of 3 mo to 5 yr. Amongst the positive samples, the predominant
      isolated was poliovirus type 1 (70.9%) from all the States. Non polio
      enteroviruses were isolated from 20.4% of fecal samples. CONCLUSION: Even though
      poliovirus is still the most common etiologic agent for acute flaccid paralysis
      in northern India, non polio enteroviruses are also emerging as important causal
      pathogens in this condition.

PMID- 9141825
TI  - Ciprofloxacin use: acute arthropathy and long-term follow up.
AB  - OBJECTIVE: To assess whether children treated with ciprofloxacin in 1990 had
      developed any permanent joint damage. DESIGN: Retrospective questionnaire-based
      follow-up study. SETTING: Adverse Drug Reaction (ADR) Monitoring Center in
      Mumbai. SUBJECTS: 3341 children treated with ciprofloxacin in 1990, including 7
      who had developed a ciprofloxacin-related acute arthropathy. METHODS: A
      questionnaire was sent in January 1995 to 147 pediatricians who had reported to
      us children in whom ciprofloxacin was prescribed in 1990. The information sought
      for included the number of children who had followed-up beyond 2 years and
      details of any joint-related complaints noted in them on long-term follow-up.
      RESULTS: Long-term follow-up was reported in 582 of these 3341 children. No joint
      related complaints had developed in 581 children, either as an acute ADR in 1990
      or as a delayed ADR during a minimum follow-up period of 2 years. Long-term
      follow-up was available in only 1 of the 7 children in whom a ciprofloxacin
      related acute arthropathy had developed in 1990, and this child was now
      asymptomatic. New information was received about 13 children treated with
      ciprofloxacin during 1991-1994 who had developed a ciprofloxacin-related acute
      arthropathy. In the total 20 children, aged 2-12 years, reported to us for acute
      ADR, the arthropathy (joint pains, restriction of joint movements and/or swelling
      of joint) had developed on day 1 to 8 of ciprofloxacin therapy, and in 18 the
      acute arthropathy had resolved within 1 day to 4 weeks of either discontinuing or
      completing ciprofloxacin therapy. Outcome in the remaining 2 children was not
      available. CONCLUSIONS: Ciprofloxacin use can cause an acute reversible
      arthropathy, but in this study there is no evidence that its use can cause a
      delayed arthropathy or any permanent joint damage.

PMID- 9141827
TI  - Headaches in children and adolescents.

PMID- 9141828
TI  - Young girl with painful joints and failing kidneys.

PMID- 9141829
TI  - Neonatal ventilation in a public sector hospital.

PMID- 9141830
TI  - Evaluation of sources and trends in pediatric medication including self
      medication.

PMID- 9141831
TI  - Status of growth monitoring activities in selected ICDS projects of Rajasthan.

PMID- 9141832
TI  - Immunoglobulin profile in breastmilk during first six months of lactation.

PMID- 9141833
TI  - Menkes' Kinky Hair disease: new considerations.

PMID- 9141834
TI  - Neonatal outcome in maternal hyperparathyroidism.

PMID- 9141835
TI  - Down's syndrome with transient myeloproliferative disorder.

PMID- 9141836
TI  - Acrodermatitis enteropathica.

PMID- 9141837
TI  - Iron deficiency anemia in pregnancy.

PMID- 9141838
TI  - Amphotericin B in visceral leishmaniasis.

PMID- 9141839
TI  - DIC in vivax malaria.

PMID- 9141840
TI  - Snake envenomation: 5 years experience in a referral hospital.

PMID- 9141841
TI  - Increasing yields from blood cultures.

PMID- 9141842
TI  - Salmonella outbreak from ice cream.

PMID- 9141843
TI  - Dengue strikes Delhi.

PMID- 9141844
TI  - WHO and UNICEF release first ever "State of the World's Vaccines" report.

PMID- 9141845
TI  - Are mosquito repellents safe?

PMID- 9141846
TI  - Role of ketotifen in bronchial asthma.

PMID- 9141847
TI  - Tuberculin test after therapy.

PMID- 9141848
TI  - Medical practice--its grey areas.

PMID- 9141849
TI  - Role of hypo-osmotic sperm swelling test in assisted reproduction.
AB  - Hypo-osmotic sperm swelling (HOS) profile is found to be a better predictor of
      the fertilisability in those husbands possessing subnormal semen parameters. The
      group where husband's HOS gradings were less than 60%, no one could conceive his
      fertile wife even after intra-uterine insemination (IUI) for 8 times. However, in
      the other group where the HOS values were greater than 60%, conception were
      registered in 6 oligospermic and 2 asthenospermic husbands after 2 to 8 IUI
      amongst 22 married couples. No conception occurred in any normal coital cycle.
      All the pregnancies were delivered by elective caesarean section (4 females and 3
      males), their birth weights were 2.705 +/- 0.425 kg. One aborted spontaneously at
      10 weeks' gestation. The emerging fact in this study is where the HOS values are
      below 60% the male fertility is reduced, the chances of conception are trivial
      but fecundity is relatively fair where HOS reading is greater than 60%. It is
      also a no risk and high benefit method to pick and choose subfertile husbands who
      are likely to conceive their fertile wives by assisted reproductive techniques.

PMID- 9141850
TI  - Significance of exercise induced increase in the diastolic pressure as an
      indicator of severe coronary artery disease.
AB  - A total of 100 patients were studied for the diastolic blood pressure response to
      treadmill exercise testing. No change in the diastolic pressure or lowering of
      the pressure was considered normal response. Seventy-four patients had normal and
      26 patients had abnormal diastolic blood pressure response. Forty patients
      underwent coronary angiography. Fifty-five per cent of the patients with normal
      diastolic pressure response had normal coronaries compared to 20% with abnormal
      response. Eleven per cent with normal response and 40% with an abnormal response
      had triple vessel disease whereas 10% with abnormal response had left main
      coronary artery disease. Exercise induced ST segment depression was almost equal
      in both groups. Hence it can be concluded that abnormal diastolic pressure
      response to treadmill exercise testing is a fairly good indicator of coronary
      artery disease irrespective of ST segment changes.

PMID- 9141851
TI  - Psychiatric profile of patients with neurodermatitis.
AB  - Fifty patients of neurodermatitis attending the dermatology clinic of a general
      hospital were screened for psychiatric morbidity. Fifty patients suffering from
      tinea from the same clinic were taken as a control group (age, sex and socio
      economic class matched). A majority of neurodermatitis patients were between 21
      30 years of age-group (52%), males (84%), married (90%), literate up to primary
      (42%) and belonged to socio-economic class V (44%). The common sites of
      neurodermatitis were legs (28%), arms (16%), scrotum (12%) or multiple sites
      (36%). The duration of symptoms ranged from 1 month to 2 years (average duration
      was 6 months). The study group also showed significantly higher occupational and
      psychosexual problems (p < 0.001). The neurodermatitis patients scored
      significantly higher on N-2 scale and Hamilton rating scale for depression.

PMID- 9141852
TI  - Evaluation of a simple technique for rapid access to left main bronchus.
AB  - A suction catheter with dual curvature at its tip was evaluated for its
      successful rapid access to left main bronchus. The catheter with dual curvature
      was passed through endotracheal tube in neutral position of head in 58 adult
      patients of both sexes in need of mechanical ventilation. Bedside x-ray (AP view)
      chest was taken to confirm its location. It is observed that this suction
      catheter had very high success rate of 95% in first attempt and 100% after
      repositioning endothracheal tube. It did not require any position alteration of
      head or body and easily allowed aspiration from left lung.

PMID- 9141853
TI  - Rational drug therapy in children.

PMID- 9141854
TI  - Lorena Bobbit--a case in point.

PMID- 9141855
TI  - Castleman's disease of broad ligament.

PMID- 9141856
TI  - Multiple meningiomas--a case report.

PMID- 9141857
TI  - Verrucous carcinoma of the vulva.

PMID- 9141859
TI  - Eye donation and IMA.

PMID- 9141858
TI  - Tension pneumocephalus complicating lumboperitoneal shunt.

PMID- 9141860
TI  - Health education.

PMID- 9141861
TI  - Disposal of bio-medical wastes.

PMID- 9141862
TI  - Blindness--the Indian scenario and plans to combat.

PMID- 9141863
TI  - Ultrasonography in acute flank pain.
AB  - In 58 patients with acute recurrent or persistent flank pain, straight x-ray
      (kidney, ureter, bladder region) detected stones in the urinary tract in 50 cases
      (86.2%), whereas ultrasonography detected stones in the urinary tract in 55
      patients (94.8%). Ultrasound also detected unilateral hydronephrosis in 20
      patients (34.48%). The presence of calculus was subsequently proved by
      intravenous urography/surgery or spontaneous passage. Ultrasonography is safe,
      quick, reliable and most effective diagnostic tool in such cases in rural areas.
      Intravenous urogram should be reserved for cases which need surgical
      intervention.

PMID- 9141864
TI  - Tumours of eyelid: a clinicopathologic study.
AB  - A retrospective study of 207 cases of eyelid tumours and tumour like lesions,
      diagnosed histopathologically, was carried out for the period 1957 to 1991. There
      was a slight preponderance of males as the male/female ratio was 1.3:1. The age
      of the cases ranged from one to 80 years. Benign tumours were usually seen in the
      first two decades whereas the malignant tumours were common in the age group of
      40 to 60 years. Malignancy was noticed in 85 cases (41.1%). Of these cases of
      malignant tumours, basal cell carcinoma was the commonest (38.8%) followed by
      sebaceous carcinoma (27.1%), squamous cell carcinoma (22.4%), basisquamous cell
      carcinoma (8.2%) and melanoma (3.5%). The ratio of basal cell carcinoma to
      squamous cell carcinoma was 1.74: 1. Of the 122 benign lesions common ones were
      vascular tumours (21.3%), neural tumours (18.0%), dermoid cysts (16.4%), squamous
      cell papilloma (13.1%) and naevi (12.3%).

PMID- 9141865
TI  - Injury to anterior optic pathways.
AB  - Fourteen patients with injury to the anterior optic pathways have been presented
      and analysed. Their clinical profile, radiological data and problems involved
      therein have been discussed. Since an expectant policy has been the rule so far,
      an attempt has been made to define the role of surgery in such cases.

PMID- 9141867
TI  - Dorsalis pedis artery: variations and clinical significance.
AB  - A variation not particularly common in the dorsalis pedis artery was noted in
      routine classroom dissection. The artery was found to be replaced by a large
      perforating branch of the peroneal artery instead of the terminal part of
      anterior tibial artery. This variation has got high clinical significance.

PMID- 9141866
TI  - Clinical significance of glycosylated haemoglobin (HbA1C) over fasting blood
      sugar for monitoring metabolic control in diabetic patients with or without
      complications.
AB  - Glycosylated haemoglobin was studied in 30 cases of mild to severe diabetes in
      the age group 12-60 years. Ten patients were keto-acidotic. Glycosylated
      haemoglobin and fasting blood sugar levels were studied in patients with various
      complications of diabetes like neuropathy, nephropathy, retinopathy, keto
      acidosis, cardiac and respiratory complications. There was a significant
      correlation between fasting blood sugar and glycosylated haemoglobin in normal
      subjects as well as in diabetic patients. There was a significant correlation
      between levels of glycosylated haemoglobin and blood sugar over preceding 4-6
      weeks. Most frequent complication being retinopathy and keto-acidosis was
      associated with maximum glycosylated haemoglobin with poor metabolic control.

PMID- 9141868
TI  - Anorexia nervosa.

PMID- 9141869
TI  - CPA presented as a syndrome.

PMID- 9141870
TI  - Fibrosarcoma of larynx.

PMID- 9141871
TI  - Acute gout in a patient taking pefloxacin--a case report.

PMID- 9141872
TI  - Anti quackery day.

PMID- 9141873
TI  - Revival of Shalya Chikitsa or acupuncture.

PMID- 9141874
TI  - Role of private practitioners in tuberculosis control in India.

PMID- 9141875
TI  - National tuberculosis control programme.

PMID- 9141876
TI  - Sensitivity of EIA in the diagnosis of tuberculosis using 38-kDa antigen.
AB  - Patients, who reported to Government Medical College Hospital, Chandigarh with
      suspected signs and symptoms of pulmonary tuberculosis, were examined. Their
      sputum was investigated for the presence of acid-fast bacilli, using the routine
      Ziehl-Neelsen staining, for 3 consecutive days. The positive cases were referred
      for treatment and the rest were referred for supplementary tests like x-ray,
      Mantoux test, FNAC and the presence of IgG antibodies in their serum against
      recombinant 38-kDa antigen derived from Mycobacterium tuberculosis, using micro
      ELISA plates. It was found that 37.8% of the cases who were negative for acid
      fast bacilli found to be positive for the presence of antimycobacterial IgG
      antibodies with an antibody titre greater than the cut off value in addition to
      one of the above mentioned positive supplementary finding. Hence, EIA for
      tuberculosis is more sensitive as compared to the routine acid-fast bacilli
      staining.

PMID- 9141877
TI  - Demonstration of acid-fast bacilli in buffy coat and bone marrow smear--a
      diagnostic tool in pulmonary tuberculosis.
AB  - Buffy coat smears prepared from peripheral blood and bone marrow aspirate
      obtained from proved 60 untreated cases of pulmonary tuberculosis were stained
      with Ziehl-Neelsen method and thoroughly screened for presence of tubercle
      bacilli. Acid-fast bacilli were detected in 55% cases in buffy coat, 48.3% cases
      in bone marrow, 38.3% cases both in buffy coat and bone marrow and 65% cases
      either in buffy coat or in bone marrow or in both. Considering the fact that
      demonstration of acid-fast bacilli may not be possible in more than 25-50% of the
      suspected cases of tuberculosis, these techniques are recommended for evaluation
      of their utility in establishing diagnosis of tuberculosis, particularly in
      reference to sputum negative cases of pulmonary tuberculosis and tuberculosis of
      inaccessible extrapulmonary sites.

PMID- 9141878
TI  - Current concept in the diagnosis and treatment of childhood pulmonary
      tuberculosis.

PMID- 9141879
TI  - Faulty prescription--an avoidable cause of multidrug resistance tuberculosis.

PMID- 9141880
TI  - Primary adenocarcinoma of the jejunum masquerading as abdominal tuberculosis.

PMID- 9141881
TI  - Tear glucose estimation--an alternative to blood glucose estimation.

PMID- 9141882
TI  - Discrimination against men in medicine.

PMID- 9141883
TI  - Is general surgery going the way of dinosaur?

PMID- 9141884
TI  - Measuring quality in general practice. Pilot study of a needs, process and
      outcome measure.
AB  - 1. As part of the Scottish Shadow Fundholding Evaluation (1990-92), quality of
      care was assessed in 6 practices with 49 general practitioners using a pre
      consultation health needs questionnaire, consultation length as a process measure
      (previously shown to be a proxy measure for quality) and a post-consultation
      satisfaction/outcome measure which contained a subset of six questions assessing
      whether patients felt enabled by their consultation. This report describes
      secondary analysis of the available dataset undertaken to explore whether the
      approach used to evaluate quality of care for patients with specific clinical
      problems could be extended to the generality of general practice consultations.
      2. Chapters 1 and 2 of the report describe earlier work developing both the
      concepts and instruments used in the Shadow Evaluation, and general findings
      already reported. The reliability and the construct validity of the measure of
      enablement are examined and found to be satisfactory. 3. Strong correlations
      between more time at consultations and more enablement for more patients are
      found at population level for patients with psychological problems, with social
      problems and with physical problems. More complex problems require more time to
      achieve equal benefit. 4. Mean consultation length and mean enablement score
      correlate well with each other and can be used as summary statistics of quality.
      Where trends require explanation or exploration, other measures of the use of
      time and the level of benefit gained are more helpful; both sets of analyses can
      be derived from the same datasets (Chapter 3). 5. Analyses at practice level show
      that practices which spend more time at consultations enable patients more
      whatever the nature of problems presented. The rank orders of time spent at
      consultation and of enablement are highly correlated (Chapter 4). 6. Analyses at
      doctor level show that doctors who spend more time at consultations enable
      patients more and that those who spend less time enable patients less. The
      numbers of patients available for study were not sufficient to explore this
      association within subgroups of clinical presentations. As in previous studies,
      we found that doctors who take longer time are likely to be more patient centred,
      and those who take less time are likely to be less patient centred. Case-mix
      varies between doctors, but seems to be independent of whether a doctor is more
      or less patient centred (Chapter 5). 7. The methods developed in this study give
      useful insights into the definition and delivery of quality of care in general
      practice (Chapter 6). The measures now need to be tested in different clinical,
      cultural and organizational settings and results compared with those found using
      routinely available NHS data on prescribing and achievement of other clinical and
      management targets (Chapter 7).

PMID- 9141885
TI  - Application of numerical descriptors to the characterization of wear particles
      obtained from joint replacements.
AB  - The application of image analysis techniques to the characterization of wear
      particles from failed joint replacements has been described. Wear particles were
      extracted from periprosthetic tissues collected during revision surgery. Chemical
      digestive methods were used to separate the wear particles from the biological
      soft material. The particles isolated were examined by optical and scanning
      electron microscopy. Digitized particle images were analysed on a Macintosh
      computer by a specially developed software and by the image analysis program
      'Prism'. The following numerical descriptors were used to characterize the
      particles: particle size, boundary fractal dimension and shape parameters such as
      form factor, roundness, convexity and aspect ratio. Elemental composition of the
      particles was determined by energy dispersive X-ray spectroscopy. Three selected
      types of wear particles were analysed and compared: titanium (Ti)-based and
      calcium (Ca)-based particles from a hip prosthesis and ultra-high molecular
      weight polyethylene (UHMWPE) particles from a knee prosthesis. The particles
      exhibited significantly different sizes and their shape numerical descriptors
      were also different. From the results obtained it appears that computer image
      analysis of wear particle morphology can be employed to determine the wear
      processes occurring in the joints. In some cases, the condition of the joint can
      also be assessed based on this analysis.

PMID- 9141886
TI  - The size and shape of particulate polyethylene wear debris in total joint
      replacements.
AB  - Osteolysis induced by wear particles has been recognized as one of the major
      causes of long-term failure in total joint replacements. However, little is
      currently known about the exact nature of particles, as the particles are too
      small to be characterized by light microscopy. In this study, ultra-high
      molecular weight polyethylene (UHMWPE) particles retrieved from ten cases (six
      cemented and four uncemented) for Freeman type conforming tibiofemoral total knee
      replacements (TKRs), three Charnley total hip replacements (THRs) and five
      Imperial College/London Hospital double cup surface hip replacements for aseptic
      loosening were extracted using a high-performance method with ultracentrifugation
      and characterized by scanning electron microscopy. The equivalent circle diameter
      (ECD) of all 18 cases ranged from 0.40 to 1.15 microns (Mean +/- SE = 0.70 +/-
      0.05 micron, median = 0.67 micron). The aspect ratio was 1.50 to 2.04 (Mean +/-
      SE = 1.75 +/- 0.04, median = 1.73), and roundness was 1.24 to 2.34 (Mean +/- SE =
      1.61 +/- 0.07, median = 1.65). The numbers of particles were 5.2 x 10(8) to 9.17
      x 10(10)/g tissue (Mean +/- SE = 1.42 x 10(10) +/- 5.41 x 10(9)/g tissue, median
      = 7.04 x 10(9)). The number of polyethylene (PE) particles/g tissue in TKRs was
      significantly larger than that in THRs (1.04 x 10(10)/g tissue and 2.16 x 10(9)/g
      tissue respectively, median, p = 0.03, Mann-Whitney U test). Unstable fixation of
      the tibial PE component might account for the accumulation of a large number of
      PE particles in the interface tissue.

PMID- 9141887
TI  - The wear of ultra-high molecular weight polyethylene sliding on metallic and
      ceramic counterfaces representative of current femoral surfaces in joint
      replacement.
AB  - A number of studies have investigated the influence of surface roughness on the
      wear of ultra-high molecular weight polyethylene (UHMWPE) in total joint
      replacement. The results of these studies have shown that the wear factor is
      proportional to the counterface roughness raised to a power greater than one. In
      this laboratory study, the effect of surface finish of several biomaterials on
      the wear of UHMWPE was studied. The study was conducted using reciprocating pin
      on-plate wear tests with bovine serum as a lubricant. The biomaterials
      investigated as the counterface material included stainless steel, cast cobalt
      chrome (CoCr), CoCr (ASTM F799), alumina ceramic and zirconia ceramic. The
      counterface topographies of the wear plates were produced using techniques
      representative of current manufacturing methods. The surface roughness of the
      wear plates was varied in the range Ra = 0.005-0.04 micron; this was
      representative of femoral heads and femoral knee components currently used
      clinically. Metals and ceramics with a similar surface roughness produced a
      similar wear rate of UHMWPE. For the limited range of smooth counterfaces used in
      this study only a moderate correlation was found between the surface roughness
      and the wear factors. For a change in counterface roughness Ra of 0.005 to 0.04
      micron, the wear factor increased from 7.4 +/- 1.6 to 16.5 +/- 2.4 x 10(-9) mm3/N
      m (mean +/- standard error). This variation in counterface roughness had much
      less effect in wear than previously reported for rougher counterfaces. For an
      extended range of counterface roughness, a stronger correlation was found using
      an exponential function for the regression fit. The exponential function shows
      the benefits of decreased wear with decreased surface roughness. Although the
      wear rate decreased less rapidly with decreased counterface roughness for Ra
      values below 0.05 micron, there were significant advantages to be gained from
      improved femoral head roughness to below 0.01 micron Ra.

PMID- 9141888
TI  - Charnley wear model for validation of hip simulators--ball diameter versus
      polytetrafluoroethylene and polyethylene wear.
AB  - Wear rates of polytetrafluoroethylene (PTFE) and polyethylene cups were compared
      in 9-channel and 12-channel simulators, using serum lubrication and gravimetric
      techniques for wear assessment. Cobalt-chromium (CoCr) and alumina ceramic
      femoral heads in 22-42 mm diameter range were used to validate simulator wear
      rates against clinical data. This was also the first study of three femoral head
      sizes evaluated concurrently in a simulator (with three replicate specimens) and
      also the first report in which any wear experiments were repeated. Fluid
      absorption artefacts were within +/-1 per cent of wear magnitude for PTFE and +/
      8 per cent for polyethylene and were corrected for. Wear rates were linear as a
      function of test duration. Precision within each set of three cups was within +/
      6 per cent. The wear rates from experiments repeated over 15 months were
      reproducible to within +/-24 per cent. However, the magnitudes of the simulator
      wear rates were not clinically accurate, the PTFE wear rates (2843 mm3/10(6)
      cycles; 22 mm diameter) were over three times higher than in vivo, the
      polyethylene 30 to 50 per cent on the low side (23 mm3/10(6) cycles; 22 mm
      diameter). Volumetric wear rate increased with respect to size of femoral head
      and a linearly increasing relationship of 7 8 per cent/mm was evident with
      respect to femoral head diameter for both PTFE and polyethylene. These data
      compared well with the clinical data.

PMID- 9141889
TI  - Development of a six station knee wear simulator and preliminary wear results.
AB  - In order to assess the wear performance of different designs of total knee
      replacements (TKR), a six station multi-axis knee simulator has been designed,
      built and commissioned. The most important features of a knee simulator are
      representative angles of flexion-extension synchronized with a dynamically
      applied load, and a combination of rolling and sliding motion. The simulator
      typically applies flexion-extension of 0-65, anterior-posterior translation of up
      to 15 mm, a dynamic load of up to 5.0 kN, and operates at 1.0 Hz. The loads and
      motions are applied using computer controlled servohydraulic actuators and hence
      their profiles are easily modified. A preliminary wear test has been conducted
      using a Kinemax (Howmedica, United Kingdom) TKR. The test was conducted in 30 per
      cent bovine serum which was changed every 150,000 cycles, at which time the
      bearing surfaces were examined and the UHMWPE tibial component was weighed. Over
      eight million cycles, a tibial wear rate of 2.62 mg/10(6) cycles was measured.
      The mild wear observed was characterized by burnishing and slight scratching in
      the anterior posterior direction. These observations are broadly in line with
      both in vitro and ex vivo studies reported in the literature for this type of
      prosthesis. Delamination wear sometimes observed in vivo was not seen.

PMID- 9141890
TI  - Factors contributing to the wear of polyethylene in clinical practice.
AB  - Wear of polyethylene is a major contributor in the failure of total joint
      replacement. A number of different factors may predispose to increased wear of
      polyethylene. These can be broadly categorized as (i) material polymorphism, (ii)
      poor design features and (iii) three-body wear. Many of these factors contribute
      to the wear encountered in clinical practice. These mechanisms are reviewed and
      examples identified in which they have resulted in increased wear.

PMID- 9141891
TI  - The pathogenesis of osteolysis in two different cementless hip replacements.
AB  - Wear of ultra-high molecular weight polyethylene has been incriminated in the
      osteolysis associated with aseptic loosening of hip implants. A variety of
      different factors can contribute to accelerated patterns of polyethylene wear and
      subsequent osteolysis. This paper examines the incidence of osteolysis observed
      in two different well-matched cohorts of cementless total hip arthroplasties. The
      patterns of osteolysis observed, which are ascribed to the generation of
      polyethylene debris, are interpreted with reference to the design of the
      individual prostheses.

PMID- 9141892
TI  - The role of polyethylene wear in joint replacement failure.
AB  - Aseptic loosening is the major cause of failure of joint replacement prostheses.
      Polyethylene implants removed at revision surgery regularly show wear. It is
      proposed that the polyethylene particles released into the tissues as a
      consequence of this wear induce a tissue response that precedes aseptic
      loosening. This paper presents the results of recent in vivo and in vitro studies
      of the biological response to polyethylene wear particles undertaken in the
      authors' laboratories. A clinical perspective is provided by the inclusion of the
      authors' recent observations of retrieval analyses of joint replacement implant
      wear and the tissue response to polyethylene in humans.

PMID- 9141893
TI  - Clinical wear behaviour of ultra-high molecular weight polyethylene cups paired
      with metal and ceramic ball heads in comparison to metal-on-metal pairings of hip
      joint replacements.
AB  - In the course of 30 years of hip endoprosthetics, a number of material
      combinations for the cups and balls of total hip prostheses have proven
      successful under clinical conditions. Favourably priced hip prostheses with
      polyethylene cups and metal balls are available for older patients with a
      moderate range of activity. Polyethylene wear of 100-300 microns/year is to be
      expected with these models. Ceramic balls (aluminium oxide for diameters 32 and
      28 mm and zirconium oxide for 22 mm) paired with polyethylene cups are
      recommended for patients with a life expectancy of 10 to 20 years, because the
      expected polyethylene wear rate with this material combination is only 50-150
      microns/year. In other words, the life cycle of the polyethylene cup is doubled,
      when it is paired with a ceramic ball. A similar polyethylene wear rate is also
      to be expected with oxygen-deep-hardened TiAlNb metal balls, which are currently
      the subject of a clinical field study. Last but not least, CoCrMoC metal-metal
      and Al2O3 ceramic ceramic pairings, which have the lowest wear rate of 2-20
      microns/year, are available for highly active patients with a life expectancy of
      more than 20 years. As far as the cup-ball pairing is concerned and under the
      current pressure of costs, the surgeon should be able to select the optimum hip
      prosthesis model for every patient from these three categories.

PMID- 9141894
TI  - Kinematics of the MATCO hip simulator and issues related to wear testing of metal
      metal implants.
AB  - Metal-metal hip implants have been used clinically in Europe to reduce the risk
      of wear particle induced osteolysis. Joint simulator devices could provide useful
      information for design improvement of the modern generation of metal-metal hip
      implants. Early wear results for metal-metal hip specimens were obtained using a
      MATCO hip simulator. A detailed kinematic analysis was developed for the MATCO
      simulator and applied to two of the wear experiments to predict the starting
      surface motion, contact zone and lubricant film thickness. It was shown that
      points on cup surfaces were not subjected to a reciprocating interaction with the
      head during wear at the beginning of testing but as wear proceeded, it was
      suggested that, in some cases, reciprocating interaction did occur on the cup
      surface. Comparison between simulator and in vivo kinematics suggested a more
      realistic representation for cup than for head wear. In the simulator, the
      Hertzian contact zone moved in a circular path over the cup surface and changed
      in size in correspondence with the applied load. Elastohydrodynamic lubrication
      was considered to be possible in the simulator, with estimated fluid film
      thickness as great as 0.1 micron. However, such thick films were not likely to
      have occurred at the start of the two wear tests which were examined in detail,
      although some mixed film lubrication might have accounted for the relatively low
      wear of one of the specimens. The inclusion of kinematic details, contact
      mechanics and elastohydrodynamic lubrication analysis in simulator testing
      protocols and in design of metal metal hip implants was recommended.

PMID- 9141895
TI  - Frictional heating of bearing materials tested in a hip joint wear simulator.
AB  - In a hip simulator wear test using bovine serum as a lubricant, the heat
      generated by ball-cup friction may cause precipitation of the proteins from the
      lubricant. The resultant accumulation of a solid layer of precipitated protein
      between the ball and cup could artificially protect the bearing surfaces from
      wear, in a manner that does not occur in vivo. Alternatively, the gradual
      depletion of the soluble proteins could interfere with their ability to act as
      boundary lubricants on the bearing surfaces, thereby artificially increasing the
      wear rate. Because the rate of protein precipitation may depend on the maximum
      temperature at the bearing surfaces during sliding, rather than the mean
      temperature of the bulk lubricant, this study determined the transient surface
      temperatures using an array of thermocouples embedded in acetabular cups of GUR
      415 ultra-high molecular weight polyethylene (UHMWPE) and femoral balls of metal
      or ceramic, in conjunction with a finite element model of the temperature
      distribution. The prostheses were tested at one cycle/s under a Paul-type,
      physiological load profile with 2030 N maximum force, with the load cycle
      synchronized to the motion cycle. The steady state temperatures of the bulk
      lubricant were 38 degrees C for the zirconia balls, 36 degrees C for the cobalt
      chromium and 33 degrees C for the alumina. However, the corresponding surface
      temperatures of the polyethylene, calculated with the finite element model, were
      99 degrees C with zirconia ceramic, 60 degrees C with cobalt-chromium alloy, and
      45 degrees C with alumina ceramic. The rank order of the surface temperatures
      corresponded to the relative amounts of protein that were precipitated in the
      test chambers during wear tests with these materials.

PMID- 9141896
TI  - Wear of the high-density polyethylene socket in total hip arthroplasty and its
      role in endosteal cavitation.
AB  - High-density polyethylene (HDP) has been used in clinical practice in total hip
      replacement since its introduction by Charnley in November 1962. Fears are being
      expressed that this may be the weakest link and the ultimate cause of failure of
      the arthroplasty. Long-term clinical experience suggests that loosening may be
      the primary cause while the presence of HDP wear particles is secondary. Healing
      of endosteal cavities can take place in the presence of HDP wear particles.

PMID- 9141897
TI  - Development of standards for orthopaedic implants.
AB  - This article reviews the need for standards for orthopaedic implants and
      illustrates the differences in approach of the European Standard Organization
      compared to National and International Standards. The areas where new work is
      being undertaken are outlined.

PMID- 9141898
TI  - A comparison between two induction regimes for the interferon treatment of
      chronic hepatitis C. Response related factors.
AB  - Treatment of chronic hepatitis C with alfa interferon for 6 months achieves
      sustained responses in 15-25% of the patients. The initial induction with higher
      doses and the prolongation of treatment can improve the results. A randomized,
      prospective study was carried out to compare the efficacy of a short term
      induction schedule of interferon alfa-2b (group A) versus a long term one (group
      B). 106 patients with chronic hepatitis C were included: 54 received 5 megaunits
      tiw for 8 weeks and 52 for 16 weeks; afterwards, interferon was reduced to 3
      megaunits up to 9 months. The percentage of sustained responses, transient
      responses and non responses were 18.5%, 24% and 57.4% in group A and 23.1%, 28.8%
      and 48.1% in group B (NS). The following factors were related to a poor response
      in the univariate analysis: an increase of serum iron levels, ferritin, Gamma-GT
      and bilirubin, anti-nuclear antibody positivity, presumed non-parenteral
      infection, an AST/ALT ratio greater than 0.75, a higher Knodell's index and a
      greater necrosis and fibrosis score. The multivariate analysis revealed that
      elevated serum iron and ferritin and anti-nuclear antibody positivity had an
      independent predictive value related to a non response. Our results appear to
      suggest that an induction with higher doses and the treatment over nine months
      are more efficient than the classic schedule. The prolongation of the induction
      period does not provide additional advantages.

PMID- 9141900
TI  - Natural history of gallbladder carcinoma: clinical and pathologic factors.
AB  - PURPOSE: To identify clinical and pathologic differences between nonadvanced
      (resectable by cholecystectomy) gallbladder adenocarcinomas (GBA) and advanced
      (nonresectable) GBA. PATIENTS AND METHODS: Twenty-nine cases of GBA were divided
      into two groups. Patients in group A (n = 15) underwent complete tumor resection
      by cholecystectomy, and those in group B (n = 14), incomplete or no resection of
      the tumor. Clinical (age, sex, pain, jaundice, weight loss, abdominal mass,
      fever), biological (anemia, hypoalbuminemia, cholestasis-cytolysis), diagnostic
      (ultrasound, intraoperative, postoperative) and pathologic (tumor size and
      differentiation status) aspects were compared in the two groups. RESULTS:
      Clinical and biological factors showed no significant differences between the two
      groups. Overall effectiveness of GC diagnosis before the postoperative pathologic
      examination was 6.7% in group A and 57.1% in group B (p < 0.001). Advanced tumors
      (T3-T4) were found in group B, and nonadvanced tumors in group A (T1-T2, 66.7%).
      In group B well-differentiated tumors (10 cases) predominated, whereas poorly
      differentiated tumors predominated in group A (19 cases, p < 0.01). CONCLUSIONS:
      The preoperative diagnosis of GBA is difficult, except in advanced cases. No
      clinical differences exist between completely resected and nonresectable tumors.
      Resected tumors are usually a postoperative pathologic finding, and are usually
      nonadvanced and well differentiated.

PMID- 9141899
TI  - Spontaneous bacterial peritonitis: clinical study, microbiological findings and
      clinical course.
AB  - One hundred and forty-four episodes of spontaneous bacterial peritonitis (SBP)
      treated in our service between July 1988 and September 1995 were studied
      retrospectively to assess the clinical presentation, microbiological findings,
      possible pathogens, treatment and course. Ascites, abdominal pain and fever were
      the most common symptoms. Only 3.5% of cases were asymptomatic. The outcome was
      fatal in 12 (8.33%). Among the factors analyzed, only a prothrombin time of less
      than 35% correlated significantly with a higher mortality rate (60% and 8.33%,
      respectively; p < 0.01). Ascitic fluid culture was positive in 43.05% of cases;
      significant differences existed between these patients and those with negative
      ascitic fluid culture with respect to clinical findings or course. Gram-negative
      microorganisms were those most frequently isolated (48.38%). Treatment was
      initiated within 12 hours in 77.7% of the patients, between 12 and 72 hours in
      11.8% and later in 10.41%. Intravenous cefotaxime was administered in 86.1% of
      cases and other drugs or drug combinations in only 13.9%; the mortality rate was
      much lower with cefotaxime (2.4% vs 45%; p < 0.01).

PMID- 9141902
TI  - Fibrinogen as a cardiovascular risk factor.

PMID- 9141901
TI  - Gallstone disease in patients over the age of 80. Surgery or long-term medical
      treatment?
AB  - OBJECTIVE: Growth in the geriatric population is increasing the biliary pathology
      of the elderly, thus becoming more frequent in the medical environment. The
      different therapeutic methods that are at present in use, should be applied to
      this group, employing open cholecystectomy as a reference. MATERIAL AND METHODS:
      During a period of 5 years we have attended 209 patients over the age of 80 (13.8
      of the total of gallstones), 76 patients (36.4%) underwent surgery and in 133
      cases (63.6%) another therapeutic method was decided upon. The progression,
      complications and mortality rate are studied closely herein. RESULTS: The
      majority, 156 (74.6%) were not previous admissions and in 108 (51.7%) the
      symptoms had been present for less than one month. Eighty four (40.2%) were
      suffering from jaundice on admission (on average 4 days) and 89 (42.6%) showed
      signs of inflammation. 23 patients (11%) were submitted only to an endoscopic
      sphincterotomy. Of those patients who underwent surgery, 52 (67.5%) had a range
      of inflammatory phenomena. Open cholecystectomy was carried out on 65 patients
      (85.5%). Sixty one patients (29.2%) presented complications, 38 (50%) in the
      group underwent surgery. Twenty eight patients (13.4%) died-9 (11.8%) of the 76
      patients were operated upon. CONCLUSIONS: Elderly patients can undergo surgery in
      selected cases with an acceptable mortality rate and high morbidity. Surgery is
      recommended in those of a lesser age, not always possible as many of them lacked
      prior symptoms.

PMID- 9141903
TI  - Tuberculosis.

PMID- 9141904
TI  - Object segregation in 8-month-old infants.
AB  - Two experiments examined 8-month-old infants' use of configural and physical
      knowledge in segregating three-dimensional adjacent displays. The infants in
      Experiment I saw two identical yellow octagons standing side by side: in the test
      events, a hand grasped the right octagon and pulled it to the side. The infants
      looked reliably longer when the octagons moved apart than when they moved
      together, suggesting that the infants (a) perceived the octagons as a single unit
      and hence (b) expected them to move together and were surprised when they did
      not. The infants in Experiment 2 saw a yellow cylinder and a blue box: a hand
      grasped the cylinder and pulled it to the side. The infants looked reliably
      longer when the box moved with the cylinder than when the box remained in place,
      suggesting that they (a) viewed the cylinder and box as distinct units and thus
      (b) expected the cylinder to move alone and were surprised when it did not. These
      results indicate that, by 8 months of age, infants use configural knowledge when
      organizing adjacent displays: they expect similar parts to belong to the same
      unit and dissimilar parts to belong to distinct units. Additional results
      revealed that 8-month-old infants' interpretation of displays is affected not
      only by configural but also by physical consideration. Thus, infants in
      Experiment 1 who saw a thin blade lowered between the octagons viewed them as two
      rather than as one unit. Similarly, infants in Experiment 2 who saw the cylinder
      lying above instead of on the apparatus floor perceived the cylinder and box as
      one rather than two units. These results indicate that 8-month-old infants bring
      to bear their knowledge of impenetrability and support when parsing adjacent
      displays. Furthermore, when faced with two conflicting interpretations of a
      display, one suggested by their configural and one by their physical knowledge,
      infants allow the latter to supersede the former. Together, these findings
      suggest that, by 8 months of age infants approach to segregation is fundamentally
      similar to that of adults.

PMID- 9141905
TI  - Pronouncing "the" as "thee" to signal problems in speaking.
AB  - In spontaneous speaking, the is normally pronounced as thuh, with the reduced
      vowel schwa (rhyming with the first syllable of about). But it is sometimes
      pronounced as thiy, with a nonreduced vowel (rhyming with see). In a large corpus
      of spontaneous English conversation, speakers were found to use thiy to signal an
      immediate suspension of speech to deal with a problem in production. Fully 81% of
      the instances of thiy in the corpus were followed by a suspension of speech,
      whereas only 7% of a matched sample of thuhs were followed by such suspensions.
      The problems people dealt with after thiy were at many levels of production,
      including articulation. word retrieval, and choice of message, but most were in
      the following nominal.

PMID- 9141906
TI  - A cross-linguistic study of early word meaning: universal ontology and linguistic
      influence.
AB  - This research concerns how children learn the distinction between substance names
      and object names. Quine (1969) proposed that children learn the distinction
      through learning the syntactic distinctions inherent in count/mass grammar.
      However, Soja et al. (1991) found that English-speaking 2-year-olds, who did not
      seem to have acquired count/mass grammar, distinguished objects from substances
      in a word extension task, suggesting a pre-linguistic ontological distinction. To
      test whether the distinction between object names and substance names is
      conceptually or linguistically driven, we repeated Soja et al.'s study with
      English- and Japanese-speaking 2-, 2.5-, and 4-year-olds and adults. Japanese
      does not make a count-mass grammatical distinction: all inanimate nouns are
      treated alike. Thus if young Japanese children made the object-substance
      distinction in word meaning, this would support the early ontology position over
      the linguistic influence position. We used three types of standards: substances
      (e.g., sand in an S-shape), simple objects (e.g., a kidney-shaped piece of
      paraffin) and complex objects (e.g., a wood whisk). The subjects learned novel
      nouns in neutral syntax denoting each standard entity. They were then asked which
      of the two alternatives--one matching in shape but not material and the other
      matching in material but not shape--would also be named by the same label. The
      results suggest the universal use of ontological knowledge in early word
      learning. Children in both languages showed differentiation between (complex)
      objects and substances as early as 2 years of age. However, there were also early
      cross-linguistic differences. American and Japanese children generalized the
      simple object instances and the substance instances differently. We speculate
      that children universally make a distinction between individuals and non
      individuals in word learning but that the nature of the categories and the
      boundary between them is influenced by language.

PMID- 9141907
TI  - Information and viewpoint dependence in face recognition.
AB  - How we recognize faces despite rotations in depth is of great interest to
      psychologists, computer scientists and neurophysiologists because of the accuracy
      of human performance despite the intrinsic difficulty of the task. Three
      experiments are reported here which used three-dimensional facial surface
      representations to investigate the effects of rotations in depth on a face
      recognition task. Experiment 1, using "shape only" representations, showed that
      all the views used (full-face, three-quarter and profile) were equally well
      recognized when all had been learned. Performance was better when the same views
      were presented in an animated sequence rather than at random, suggesting that
      structure-from-motion provides useful information for recognition. When stimuli
      were presented inverted, performance was worse and there were differences in the
      recognizability of views, demonstrating that the familiarity of upright faces
      affects generalization across views. Experiments 2 and 3 investigated
      generalization from single views and found performance to be dependent on learned
      view. In both experiments, generalization from learned full-face fell off with
      increasing angle of rotation. With shape only stimuli, three-quarter views
      generalized well to each other, even when inverted but for profiles
      generalization was equally bad to all unlearned views. This difference may be
      explained because of the particular relationship of the profile to the axis of
      symmetry. In Experiment 3, addition of information about superficial properties
      including color and texture facilitated performance, but patterns of
      generalization remained substantially the same, emphasizing the importance of
      underlying shape information. However, generalization from the three-quarter view
      became viewpoint invariant and there was some evidence for better generalization
      between profiles. The results are interpreted as showing that three-dimensional
      shape information is fundamental for recognition across rotations in depth
      although superficial information may also be used to reduce viewpoint dependence.

PMID- 9141908
TI  - Associative and semantic priming effects occur at very short stimulus-onset
      asynchronies in lexical decision and naming.
AB  - Prior research has found significant associative/semantic priming effects at very
      short stimulus-onset asynchronies (SOAs) in experimental tasks such as lexical
      decision, but not in naming tasks (however, see Lukatela and Turvey, 1994). In
      this paper, the time course of associative priming effects was analyzed a several
      very short SOAs (33, 50, and 67 ms), using the masked priming paradigm (Forster
      and Davis, 1984), both in lexical decision (Experiment 1) and naming (Experiment
      2). The results show small--but significant--associative priming effects in both
      tasks. Additionally, using the masked priming procedure at the 67 ms SOA.
      Experiments 3 and 4, shows facilitatory priming effects for both associatively
      and semantically (unassociated) related pairs in lexical decision and naming
      tasks. That is, automatic priming can be semantic. Taken together our data appear
      to support interactive models of word recognition in which semantic activation
      may influence the early stages of word processing.

PMID- 9141911
TI  - Spatial learning by rats across visually disconnected environments.
AB  - Two spatial tasks were designed to test specific properties of spatial
      representation in rats. In the first task, rats were trained to locate an escape
      hole at a fixed position in a visually homogeneous arena. This arena was
      connected with a periphery where a full view of the room environment existed.
      Therefore, rats were dependent on their memory trace of the previous position in
      the periphery to discriminate a position within the central region. Under these
      experimental conditions, the test animals showed a significant discrimination of
      the training position without a specific local view. In the second task, rats
      were trained in a radial maze consisting of tunnels that were transparent at
      their distal ends only. Because the central part of the maze was non-transparent,
      rats had to plan and execute appropriate trajectories without specific visual
      feedback from the environment. This situation was intended to encourage the
      reliance on prospective memory of the non-visited arms in selecting the following
      move. Our results show that acquisition performance was only slightly decreased
      compared to that shown in a completely transparent maze and considerably higher
      than in a translucent maze or in darkness. These two series of experiments
      indicate (1) that rats can learn about the relative position of different places
      with no common visual panorama, and (2) that they are able to plan and execute a
      sequence of visits to several places without direct visual feed-back about their
      relative position.

PMID- 9141912
TI  - Temporal bisection in humans with longer stimulus durations.
AB  - Normal adults were tested in eight temporal bisection conditions, using 500-Hz
      tones as stimuli. Stimulus lengths matched, or overlapped with, durations
      normally used in bisection experiments with animals, and chronometric counting
      was prevented by using a concurrent digit-shadowing task. Four experimental
      groups were used to investigate any effects of stimulus spacing, and stimuli were
      logarithmically or linearly spaced between standard "short" and "long" durations
      of 1 and 4, or 2 and 8 sec. A slight leftward shift of the psychophysical
      function was found in the logarithmic spacing condition, relative to linear
      spacing. Four other groups tested the conjecture that the ratio of the short and
      long standards might play some role in determining the location of the bisection
      point, and conditions with long/short ratios of 2:1 and 5:1 were used. In all
      cases the bisection point was close to the arithmetic mean of the short and long
      standards, rather than the geometric mean, as in animal studies. Overall,
      however, smaller long/short ratios (which may indicate more difficult temporal
      discriminations) produced more sensitive timing. When the long/short ratio was
      held constant, however, data showed nearly perfect superimposition, indicating
      conformity to scalar timing. In general, results were similar to those from
      experiments with humans that used much shorter durations, indicating the
      animal/human differences in bisection do not depend on the absolute lengths of
      the stimuli used.

PMID- 9141913
TI  - Hemodynamic effects of anesthesia in patients with ischemic heart failure
      chronically treated with angiotensin-converting enzyme inhibitors.
AB  - Anesthesia may induce hemodynamic instability in patients treated with
      angiotensin-converting enzyme inhibitors (ACEIs). To assess the hemodynamic
      effects of anesthesia in patients treated (n = 9) or not treated (n = 9) with
      ACEIs for ischemic left ventricle dysfunction after myocardial infarction, we
      studied 18 patients scheduled for elective coronary artery bypass graft surgery.
      Induction of anesthesia with fentanyl (5 micrograms/kg), flunitrazepam (30
      micrograms/kg), and pancuronium (100 micrograms/kg) was followed by a significant
      decrease in mean arterial blood pressure in both groups (-18.6% +/- 8.1% in
      controls and -25.7% +/- 7.8% in ACEI-treated patients, P = 0.01). In controls,
      cardiac index and systemic vascular resistance were not significantly altered (
      11.2% +/- 9.4% and -16.2% +/- 4.6%, respectively, not significant [NS]). In ACEI
      treated patients, cardiac index decreased significantly (-27.3% +/- 11.6%, P =
      0.01 from baseline and P = 0.03 when compared with controls), and systemic
      vascular resistance was unchanged (1.0% +/- 18.7%, NS from baseline and P = 0.04
      when compared with controls). Two patients from each group experienced a
      transient severe hypotensive episode. ACEI treatment in patients with infarction
      induced myocardial dysfunction does not increase the incidence of severe
      hypotension after induction of anesthesia.

PMID- 9141914
TI  - Effects of dopexamine on creatinine clearance, systemic inflammation, and
      splanchnic oxygenation in patients undergoing coronary artery bypass grafting.
AB  - Impairment of splanchnic and peripheral tissue perfusion during cardiopulmonary
      bypass (CPB) may be responsible for endotoxin-mediated systemic inflammation and
      acute phase responses. We examined the effects of dopexamine on hemodynamic
      parameters, creatinine clearance, systemic and splanchnic oxygenation, gastric
      mucosal pH (pHi), and mixed and hepatic venous plasma levels of endotoxin,
      interleukin-6 (IL-6), serum amyloid A (SAA), and C-reactive protein (CRP) in 44
      patients scheduled for coronary artery bypass grafting. Patients were randomized
      to receive continuous infusions of 0.5, 1.0, or 2 micrograms.kg-1.min-1
      dopexamine (n = 10 per group) or placebo (n = 14) prior to surgery,
      intraoperatively, and postoperatively. Dopexamine infusion increased systemic
      oxygen delivery (P < or = 0.01). Hepatic venous oxygen saturation did not change,
      and pHi decreased during and after CPB in all patients (P < or = 0.01).
      Postoperative increases in IL-6 were smallest in patients who received 2.0
      micrograms.kg-1.min-1 dopexamine (P < or = 0.02). SAA and CRP increases during
      the postoperative period were less pronounced with dopexamine throughout the
      study. Creatinine clearance was elevated in all dopexamine groups (P < or =
      0.025). This elevation was higher with lower dopexamine doses (P < or = 0.025).
      We conclude that dopexamine improves creatinine clearance and reduces systemic
      inflammation without affecting splanchnic oxygenation.

PMID- 9141915
TI  - Arterial pressure-flow relationship in patients undergoing cardiopulmonary
      bypass.
AB  - We determined the arterial pressure-flow relationship experimentally by means of
      step changes of blood flow in 30 adult patients undergoing cardiopulmonary bypass
      (CPB). Anesthesia technique was uniform. CPB was nonpulsatile; hypothermia to 25
      28 degrees C, and hemodilution to 18%-25% hematocrit were used. During stable
      bypass, mean arterial pressure was recorded first with blood flow 2.2 L.min-1.m
      2. Flow was then increased to 2.9 L.min-1.m-2 for 10 s and reverted to baseline
      for 1 min. Then it was decreased to 1.45 L.min-1.m-2 for 10 s, and reverted to
      baseline for 1 min. Subsequently, it was decreased to 0.73 L.min-1.m-2 for 10 s
      and then reverted to baseline. Similar sets of measurements were repeated after
      0.25 mg of phenylephrine and once the patient was rewarmed. The pressure-flow
      function was individually determined by regression, and the critical pressure
      estimated by extrapolation to zero flow. All patients had zero-flow critical
      pressure during hypothermia, with a mean value of 21.8 +/- 6.4 mm Hg (range 8.8
      38.9). It increased after 0.25 mg phenylephrine to 25.4 +/- 7.2 mm Hg (range 12.2
      43.9, P < 0.001). During normothermia, critical pressure was 21.2 +/- 5 mm Hg
      (range 13.4-30.9), not significantly different from hypothermia. During
      hypothermia, the slope of the pressure-flow function (i.e., resistance) was 14.9
      +/- 3.5 mm Hg.L-1.min-1.m-2 (range 7.6-22.1). It increased significantly (P <
      0.001) after phenylephrine, to 19.7 +/- 6.2 mm Hg.L-1.min-1.m-2 (range 11.4
      40.5), and returned to 15.4 +/- 3.4 mm Hg.L-1.min-1.m-2 (range 10.1-24.2) during
      normothermic bypass. Systemic vascular resistance appeared to vary reciprocally
      with blood flow, although this finding may represent a mathematical artifact,
      which can be avoided by using zero-flow critical pressure in the vascular
      resistance equation.

PMID- 9141916
TI  - Age-related propofol effects on electrophysiological properties of isolated
      hearts.
AB  - We compared the direct effects of propofol on the conduction system of neonatal
      (< 7 days) and adult (> 3 mo) rabbit hearts using intracardiac recording/
      stimulation in Langendorff-perfusion and autonomic blockade. At a low
      concentration (3 microM), propofol caused a slight but significant lengthening of
      the atrio-ventricular (AV) conduction interval of the adult hearts, but not of
      neonatal hearts. At a higher concentration (10 microM and above), propofol
      significantly prolonged the AV conduction interval in a frequency-dependent
      manner in both neonates and adults. The AV Wenckebach cycle length was also
      lengthened, with the change more significant in the adults. However, with
      concentrations of propofol up to 100 microM, the neonatal hearts frequently (9 of
      13 experiments) progressed to complete AV block, which was not observed in the
      adults. Conduction through the atrial tissue (SA interval) and the His-Purkinje
      system (HV interval), as well as the spontaneous heart rate, were all slowed by
      propofol at 30 microM or above. However, the lengthening of SA interval was more
      pronounced in the neonates, and only in the neonate was the atrial refractory
      period prolonged by propofol at 10 microM and above. We conclude that 3 microM
      propofol produces no significant direct effects on the neonatal cardiac
      electrophysiological properties, although AV conduction of the adult heart may be
      suppressed at this concentration of propofol. At higher concentrations, age
      related propofol effects were demonstrated in the AV node and the atrial tissue.

PMID- 9141917
TI  - Global ischemia increases the density of voltage-dependent calcium channels in
      porcine cardiac sarcolemma.
AB  - The objective of this work was to determine whether normothermic global cardiac
      ischemia in a porcine model was associated with a change in the density (Bmax) of
      voltage-dependent calcium channels in myocardial sarcolemmal membranes. Pigs were
      anesthetized, a thoracotomy was performed, and samples were taken of the left and
      right ventricles from control and ischemic hearts. Dihydropyridine-binding sites
      were quantified using [3H]isradipine, and 5'-nucleotidase activity was measured
      by the liberation of inorganic phosphate from adenosine monophosphate. Bmax and
      dissociation constants and 5'-nucleotidase activity for control and ischemic
      tissues, respectively, were compared by using Student's t-test for unpaired
      samples. After normothermic global ischemia, the Bmax of [3H]isradipine binding
      increased in the left ventricle by 81% (299% +/- 1.7% to 540% +/- 11% fmoles/mg,
      P < 0.01) and in the right ventricle by 33% (387% +/- 9.9% to 515% +/- 38%
      fmoles/mg, P < 0.01) compared with control. 5'-nucleotidase activity increased by
      48% in the left ventricle and by 96% in the right ventricle (p < 0.05). Fifteen
      minutes of normothermic ischemia in the pig is associated with marked sarcolemmal
      abnormalities, including increases in specific dihydropyridine binding and 5'
      nucleotidase activity, which reflect global changes in membrane function, which
      might contribute to the increase in myoplasmic calcium during ischemia.

PMID- 9141918
TI  - Early hemodynamic effects of left atrial administration of epinephrine after
      cardiac transplantation.
AB  - We studied the hemodynamic effects of left atrial (LA) administration of
      epinephrine in 10 patients after cardiac transplantation, using a prospective,
      randomized, double-blind, cross-over design. After allograft implantation, a LA
      catheter was inserted and epinephrine infusion commenced at 100 ng.kg-1.min-1.
      Each trial period consisted of 20 min, with the LA and right atrial (RA) lines
      switched over between each period; hemodynamic measurements were taken after each
      time period. Whether epinephrine was administered via the RA or LA did not
      significantly alter hemodynamics (RA versus LA): mean (SD) arterial blood
      pressure 67 (7.5) vs 64 (9.5) mm Hg (P = 0.16), mean pulmonary artery pressure 22
      (4.0) vs 21 (9.4) mm Hg (P = 0.67), cardiac index 3.2 (1.1) vs 3.2 (1.1) L.min
      1.m-2 (P = 0.83), pulmonary vascular resistance index 308 (157) vs 345 (157)
      dynes.s.cm-5/m-2 (P = 0.30) or right ventricular ejection fraction 35% (11%) vs
      32% (9.8%) (P = 0.23). Arterial epinephrine plasma levels were similar (P =
      0.16). There was no significant pulmonary extraction of measured catecholamines.
      We observed no hemodynamic benefit of LA epinephrine administration. It may be
      that the cardiac transplantation population reacts differently compared with
      other cardiac surgical patients (possibly because pulmonary extraction of
      catecholamines is reduced). Because we did not observe a hemodynamic advantage in
      patients immediately after cardiac transplantation, we would not recommend the
      use of LA epinephrine at the dose studied.

PMID- 9141919
TI  - A randomized multicenter study of remifentanil compared with alfentanil,
      isoflurane, or propofol in anesthetized pediatric patients undergoing elective
      strabismus surgery.
AB  - Remifentanil hydrochloride is a new, ultrashort-acting opioid metabolized by
      nonspecific plasma and tissue esterases. We conducted this multicenter study to
      examine the hemodynamic response and recovery profile of premedicated children
      undergoing strabismus repair who were randomly assigned to receive one of four
      treatment drugs (remifentanil, alfentanil, isoflurane, or propofol) along with
      nitrous oxide and oxygen for maintenance of anesthesia. Induction of anesthesia
      was by nitrous oxide, oxygen, and halothane or nitrous oxide, oxygen, and
      propofol. Anesthesia was then maintained with remifentanil 1.0 microgram/kg over
      30-60 s, followed by a constant infusion of 1.0 microgram.kg-1.min-1, alfentanil
      100 micrograms/kg bolus followed by a constant infusion of 2.5 micrograms.kg
      1.min-1, propofol 2.5 mg/kg bolus followed by a constant infusion of 200
      micrograms.kg-1.min-1, or isoflurane 1.0 minimum alveolar anesthetic
      concentration. The infusions of the anesthetics and the administration of the
      inhaled gases were adjusted clinically by predetermined protocols. Elapsed time
      intervals from the end of surgery to the time the patients were tracheally
      extubated and displayed purposeful movement, as well as the time the patients met
      the postanesthesia care unit (PACU) and hospital discharge times, were recorded.
      Heart rate and systolic and diastolic blood pressure were measured at fixed
      intervals. In addition, cardiovascular side effects (bradycardia, hypotension,
      and hypertension) as well as vomiting, pruritus, agitation, and postoperative
      hypoxemia were also noted. There were no significant differences in patient
      demographics among the treatment groups. There was no difference in the early
      recovery variables (times to extubation and purposeful movement) or the times to
      PACU and hospital discharge among groups. There were significant differences in
      side effects among the groups. Patients who received remifentanil had higher PACU
      objective pain-discomfort scores than those who received alfentanil and propofol.
      Patients anesthetized with alfentanil had a greater incidence in the use of
      naloxone and a greater incidence of postoperative hypoxemia compared with those
      anesthetized with remifentanil. The incidence of postoperative hypoxemia was the
      same for remifentanil, propofol, and isoflurane groups. There were no significant
      differences in the incidence of emesis among the four groups, and all four groups
      had similar hemodynamic profiles. We conclude that remifentanil appears to be an
      effective drug for anesthesia. Its hemodynamic and recovery profile appear
      similar to other comparable drugs. Based on previous pharmacokinetic studies, the
      1.0 microgram.kg-1.min-1 infusion may be twice the 50% effective dose observed in
      adults. In this study, the relative "overdose" of remifentanil was well tolerated
      and did not prolong recovery.

PMID- 9141920
TI  - The efficacy of tranexamic acid versus placebo in decreasing blood loss in
      pediatric patients undergoing repeat cardiac surgery.
AB  - The antifibrinolytic drug, tranexamic acid, decreases blood loss in adult
      patients undergoing cardiac surgery. However, its efficacy has not been
      extensively studied in children. Using a prospective, randomized, double-blind
      study design, we examined 41 children undergoing repeat sternotomy for repair of
      congenital heart defects. After induction of anesthesia and prior to skin
      incision, patients received either tranexamic acid (100 mg/kg, followed by 10
      mg.kg-1.h-1) or saline placebo. At the onset of cardiopulmonary bypass, a second
      bolus of tranexamic acid (100 mg/kg) or placebo was administered. Total blood
      loss and transfusion requirements during the period from protamine administration
      until 24 h after admission to the intensive care unit were recorded. Children who
      were treated with tranexamic acid had 24% less total blood loss (26 +/- 7 vs 34
      +/- 17 mL/kg) compared with children who received placebo (univariate analysis P
      = 0.03 and multivariate analysis P < 0.01). Additionally, the total transfusion
      requirements, total donor unit exposure, and financial cost of blood components
      were less in the tranexamic acid group. In conclusion, tranexamic acid can reduce
      perioperative blood loss in children undergoing repeat cardiac surgery.

PMID- 9141921
TI  - Modulation of ischemic excitatory neurotransmitter and gamma-aminobutyric acid
      release during global temporary cerebral ischemia by selective neuronal nitric
      oxide synthase inhibition.
AB  - Nitric oxide release during cerebral ischemia is the result of both neuronal and
      endothelial subclasses of nitric oxide synthase (NOS). In this study, we examined
      the role of specific neuronal NOS inhibition (nNOSI) on excitatory
      neurotransmitter and gamma-aminobutyric acid (GABA) release during global
      cerebral ischemia. Microdialysis probes were placed into the striatum of 24 rats.
      After probe stabilization, rats were randomized to receive 7-nitroindazole (7
      NI), a selective nNOSI, in doses of 0, 5, 10, or 20 mg/kg. Temporary global
      forebrain ischemia was induced for 15 min, followed by 60 min of reperfusion.
      nNOSI administration did not produce detectable changes in neurotransmitter
      recovery prior to ischemia. There were significant increases in aspartate (ASP),
      glutamate (GLU), glycine (GLY), and GABA recovery during ischemia in the absence
      of nNOSI. 7-NI resulted in an attenuation in GLU, GLY, and GABA recovery during
      ischemia and reperfusion. No differences in ASP recovery were detected with
      nNOSI. Differences between the present study and other studies that examine the
      role of nonspecific constitutive NOSI during cerebral ischemia demonstrate the
      contribution of neuronal NOS on the modulation of ischemic excitatory
      neurotransmitter and GABA release.

PMID- 9141922
TI  - Modulation of ischemic excitatory neurotransmitter and gamma-aminobutyric acid
      release during global temporary cerebral ischemia by local nitric oxide synthase
      inhibition.
AB  - Systemic nitric oxide synthase inhibition (NOSI) decreases cerebral blood flow,
      which may worsen ischemic insults. To examine the local effects of NOSI without
      this confounding effect, we examined the role of a locally administered NOSI, NG
      nitro-L-arginine-methyl-ester (L-NAME), on neurotransmitter recovery during
      cerebral ischemia. Rats were assigned to one of three groups: locally
      administered L-NAME via a striatal microdialysis probe (n = 11), systemic L-NAME
      (n = 5), or control (n = 11). Temporary global forebrain ischemia was induced for
      15 min, followed by 60 min of reperfusion. L-NAME resulted in decreases of basal
      aspartate (ASP; 74% of basal) and glutamate (GLU; 60% of basal) recovery. While
      systemic L-NAME caused significant increases in ischemic ASP and GLU recovery (by
      224% and 110%, respectively, compared with ischemic controls), local NOSI
      administration resulted in a significant attenuation of peak ASP, GLU, glycine,
      and gamma-aminobutyric acid recovery (43%, 38%, 53%, and 72%, respectively,
      compared with ischemic controls). We conclude that local NOSI attenuated ischemic
      neurotransmitter recovery during ischemia/reperfusion. Our results emphasize the
      importance of the systemic effects of NOSI and suggest both deleterious and
      beneficial effects of NOSI during ischemia/reperfusion.

PMID- 9141924
TI  - Hepatic disposition of alfentanil and sufentanil in patients undergoing
      orthotopic liver transplantation.
AB  - Alfentanil and sufentanil are used in the anesthetic management of patients
      undergoing orthotopic liver transplantation (OLT) and are extensively metabolized
      by the liver. We examined the influence of OLT on the removal of these opioids.
      14 patients undergoing OLT were given either alfentanil (40 micrograms/kg
      intravenous [IV] bolus) or sufentanil (5 micrograms/kg IV bolus) during the
      induction of anesthesia, followed by infusion during surgery (1 microgram.kg
      1.min-1 alfentanil or 0.01 microgram.kg-1.min-1 sufentanil) and the postoperative
      period (0.5 microgram.kg-1.min-1 or 0.005 microgram.kg-1.min-1). A catheter was
      inserted into the hepatic vein to determine the drugs' hepatic extraction
      coefficient and hepatic clearance. The hepatic extraction coefficient was 0.14
      for alfentanil and 0.35 for sufentanil. The total and hepatic clearance of
      alfentanil were similar, while the hepatic clearance of sufentanil was 50% of the
      total clearance (P < 0.05). The total clearance of alfentanil was significantly
      linked to its hepatic clearance (r2 = 0.81, P < 0.001). We conclude that the
      total clearance of sufentanil is greater than its hepatic clearance. This
      difference suggests that there is extrahepatic metabolism of sufentanil in
      patients undergoing OLT.

PMID- 9141923
TI  - Dose-ranging study in younger adult and elderly patients of ORG 9487, a new,
      rapid-onset, short-duration muscle relaxant.
AB  - The purpose of this multicenter, randomized, assessorblind placebo-controlled
      study was to determine which of five doses of the new, rapid-onset neuromuscular
      relaxant, ORG 9487, provided both good to excellent tracheal intubating
      conditions 60 s after administration and a clinical duration of action < 20 min
      in 120 younger (aged 18-64 yr) and 61 elderly (aged 65-85 yr) adult patients.
      Anesthesia was induced with fentanyl (2-5 micrograms/kg) and thiopental (3-6
      mg/kg) and maintained with N2O/O2 and a propofol infusion (50-300 micrograms.kg
      1.min-1). Neuromuscular train-of-four (TOF) monitoring by electromyography (Datex
      Relaxograph) commenced immediately after anesthetic induction and was followed,
      within 30 s, by one of five doses of ORG 9487 (0.5, 1.0, 1.5, 2.0, 2.5 mg/kg) or
      a placebo. Tracheal intubation was attempted at 60 s and again, in the case of
      failure, at 90 s. Conditions were assessed with a 4-point scale. Maximum block,
      clinical duration (time to 25% T1 recovery), and recovery (TOF > or = 0.7) were
      measured. Dose-dependent changes were observed in tracheal intubating conditions
      and neuromuscular block. Good to excellent intubating conditions at 60 s were
      present in most younger adult (52 of 60) and elderly (26 of 31) patients
      administered doses > or = 1.5 mg/kg. Mean clinical durations < 20 min were
      observed in adult patients at doses up to 2.0 mg/kg and in geriatric patients up
      to 1.5 mg/kg. Thus, doses of 1.5-2.0 mg/kg ORG 9487 enabled both rapid tracheal
      intubation and a short clinical duration of action in adult and elderly patients.

PMID- 9141925
TI  - Respiratory mechanics, gastric insufflation pressure, and air leakage of the
      laryngeal mask airway.
AB  - A potential risk of the laryngeal mask airway (LMA) is incomplete mask seal,
      which causes air leakage or insufflation of air into the stomach. The objective
      of the present study was to assess respiratory mechanics, quantify air leakage,
      and measure gastric air insufflation in patients ventilated via the LMA. Thirty
      patients were studied after induction of anesthesia but prior to any surgical
      manipulations. After the insertion of the LMA, patients were ventilated with
      increasing tidal volumes until one of the three following end points were
      reached: 1) gastric air insufflation, 2) airway pressure > 40 cm H2O, or 3)
      limitation of further increase in tidal volume by air leakage. The following
      variables were determined:inspired volume (VI), expired volume (VE), maximum
      inspiratory pressure (Pmax), airway pressure at gastric inflation (Pinfl),
      respiratory time constant (RC), compliance (C), resistance (R), and leakage
      fraction (FL). Respiratory mechanics were in the physiological range. Gastric
      insufflation occurred in 27% of the patients at inspiratory pressures between 19
      and 33 cm H2O. Air leakage of more than 10% was evident at inspiratory pressures
      between 25 and 34 cm H2O. The end point of 40 cm H2O airway pressure was reached
      in only three patients. We conclude that the LMA is not better in preventing
      airway pressure transmission to the esophagus than a conventional face mask.
      However, a high FL is associated with reduced gastric air insufflation.

PMID- 9141926
TI  - The threshold for thermoregulatory vasoconstriction during nitrous
      oxide/sevoflurane anesthesia is reduced in the elderly.
AB  - Elderly patients become more hypothermic during surgery, shiver less
      postoperatively, and take longer to rewarm than younger patients. Similarly, the
      vasoconstriction threshold (triggering core temperature) is reduced approximately
      1 degree C in elderly patients during nitrous oxide/isoflurane anesthesia.
      Accordingly, we tested the hypothesis that the vasoconstriction threshold in the
      elderly is also reduced approximately 1 degree C during nitrous oxide and
      sevoflurane anesthesia. Eleven young patients aged 30-50 yr and 14 elderly
      patients aged 60-80 yr were anesthetized with nitrous oxide (50%) and sevoflurane
      (1%). Mean skin temperature was calculated from four sites. Fingertip blood flow
      was estimated using forearm minus fingertip skin-temperature gradients, with a
      gradient of 0 degree C identifying onset of vasoconstriction. The distal
      esophageal temperature triggering onset of vasoconstriction identified the
      threshold for this thermoregulatory defense. The data from five patients who did
      not vasoconstrict at minimum core temperatures of 33-34 degrees C were
      eliminated, leaving 10 patients in each group. The vasoconstriction threshold was
      significantly less in the elderly (35.0 +/- 0.8 degrees C) than in younger
      patients (35.8 +/- 0.3 degrees C), despite similar mean skin temperatures (mean
      +/- SD, P < 0.01, Student's t-test). Age dependence of thermoregulatory
      vasoconstriction during nitrous oxide/sevoflurane anesthesia is similar to that
      previously observed during nitrous oxide/isoflurane anesthesia.

PMID- 9141927
TI  - Airway pressure changes during one-lung ventilation.
AB  - This investigation analyzed the changes in inspiratory airway pressures during
      transition from two-lung to one-lung ventilation in patients tracheally intubated
      with a double-lumen endotracheal tube (DLT) using a classical method of
      intubation without fiberoptic bronchoscopy. All patients were anesthetized in a
      standardized fashion. Ventilation was accomplished with the Siemens 900 constant
      flow mechanical ventilator (Solna, Sweden). Peak (Ppeak) and plateau (Pplateau)
      inspiratory airway pressures were recorded with an on-line respiratory monitor
      before and after clamping the tracheal limb of the DLT. The position of the DLTs
      was evaluated by fiberoptic bronchoscopy with the patient in supine position. Of
      the 51 intubations, the DLT was malpositioned in 15 cases (29.5%). Ppeak and
      Pplateau increased significantly when switched from two-lung ventilation to one
      lung ventilation in both correctly and incorrectly positioned DLTs. When the DLT
      was in a correct position, Ppeak increased by a mean of 55.1% and Pplateau
      increased by a mean of 41.9%. When the DLT was malpositioned, this increase was
      significantly larger (74.9% and 68.8%, respectively). Three tests commonly used
      as markers of malpositioned DLTs were evaluated based on the data of this study,
      and it was established that, although the pressure differences related to
      position are statistically significant, as a single value, they cannot be used
      for clinical decision making.

PMID- 9141928
TI  - Malignant hyperthermia testing in patients with persistently increased serum
      creatine kinase levels.
AB  - We describe 49 neurologically asymptomatic patients with persistently increased
      serum creatine kinase (CK) levels (idiopathic hyperCKemia or IHCK) who were
      referred to our institution for diagnostic muscle biopsy, including malignant
      hyperthermia (MH) susceptibility testing between 1979 and 1993. Muscle biopsy
      samples of the vastus lateralis were obtained for histologic analysis and MH
      contracture testing with halothane and caffeine. From 1979 to November 1987,
      patients were tested for MH in accordance with a standardized institutional
      protocol. After November 1987, contracture testing was performed according to the
      recently adopted North American MH Group protocol. In both protocols, a patient
      was considered to be MH susceptible (MHS) if one or more muscle strip
      demonstrated an abnormal contracture response after exposure to 3% halothane, 2%
      halothane, or caffeine alone. Twenty-four of the 49 IHCK patients (49%) had
      positive contracture tests. No significant correlation was found between the
      magnitude of CK increase and the incidence of MHS or histologic abnormalities.
      Unexplained persistently increased CK levels in an otherwise healthy patient
      should alert the anesthesiologist to the possibility of MHS and/or myopathy.

PMID- 9141929
TI  - Anesthetic potencies of n-alkanols: results of additivity and solubility studies
      suggest a mechanism of action similar to that for conventional inhaled
      anesthetics.
AB  - The mechanism by which n-alkanols produce anesthesia and the characteristics
      relevant to those mechanisms (e.g., lipid solubilities versus potencies) remain
      unknown. Accordingly, we determined potencies (minimum alveolar anesthetic
      concentration [MAC]) and solubilities of normal methanol, ethanol, butanol,
      hexanol, and octanol. We also determined the additivity of these alkanols with a
      conventional anesthetic (desflurane) and the additivity of methanol with butanol.
      Finally, we determined whether alkanol metabolism influences alkanol potencies.
      MAC for methanol, ethanol, butanol, hexanol, and octanol (0.00200, 0.000989,
      0.000133, 0.0000214, and 0.00000117 atm, respectively) increased with an
      increasing solubility in olive oil (olive oil/gas partition coefficients 48.6,
      108, 1,650, 11,600, and 93,500, respectively) and octanol (octanol/gas partition
      coefficients 163, 1,150, 22,900, 135,000, and 4,140,000) to give a product of MAC
      x solubility for olive oil approximately 10 times less (values of 0.10-0.25) than
      that expected from the Meyer-Overton hypothesis (compared with conventional
      inhaled anesthetics). There was less deviation for octanol, but the results were
      more variable. Inhibition of methanol and butanol metabolism by 4-methylpyrazole
      did not alter MAC. Methanol, ethanol, butanol, hexanol, and octanol had
      approximately additive anesthetic effects with desflurane, with some small but
      statistically significant deviations both above and below additivity. In the
      presence of 0.5 MAC of desflurane, we needed to add 0.4-0.6 MAC of each alkanol
      to inhibit the movement of 50% of the rats in response to noxious stimulation.
      Similarly, the effects of methanol and butanol were additive (with each other).
      The saline/gas partition coefficient for each alkanol was high (3700, 2650, 1400,
      900, and 709 for methanol through octanol), which indicates high polarity. We
      conclude that the potent anesthetic effects of normal alkanols may result from an
      affinity to both polar and nonpolar phases. Our finding of additivity of alkanols
      with each other is consistent with a common mechanism of action. Similarly, the
      finding of additivity or slight deviations from additivity for alkanols with
      desflurane is consistent with mechanisms of action that have much in common.

PMID- 9141930
TI  - Performance of computer-assisted continuous infusion at low concentrations of
      intravenous sedatives.
AB  - We studied the performance of a target-controlled drug infusion device, computer
      assisted continuous infusion (CACI). Forty-one volunteers received one of
      midazolam (n = 11), propofol (n = 10), thiopental (n = 10), or fentanyl (n = 10)
      in sedative concentrations. Concentrations were kept constant for 45-70 min at
      five sequential target concentrations in each subject. Twenty-six subjects had
      arterial sampling and 15 had venous sampling to determine drug concentrations.
      Median performance errors, median absolute performance error (MDAPE), wobble,
      divergence, and median absolute constancy error (MDACE), defined as error around
      mean actual concentration at each target, were calculated. CACI demonstrated
      significant performance errors, which were different among drugs. MDAPE (5%-95%
      confidence interval) ranged from 22.9% (12.1%-39.6%) for propofol to 82.2% (36.0%
      183.0%) for midazolam. Although performance errors could be large, CACI was able
      to maintain a constant serum concentration over time very successfully. The MDACE
      ranged from 5.6% (3.9%-17.3%) for fentanyl to 11.2% (8.9%-20.4%) for propofol.
      Few differences occurred between arterial and venous sampling, although when they
      occurred, arterial samples indicated larger errors. It is concluded that CACI is
      very successful at maintaining constant serum concentrations of these drugs at
      sedative concentrations. Arterial sampling should be used when the performance
      characteristics of an infusion device are being tested. However, venous sampling
      may be adequate to determine serum concentrations when a pseudo-steady state has
      been achieved.

PMID- 9141931
TI  - Comparison between conventional axillary block and a new approach at the
      midhumeral level.
AB  - We undertook this prospective, randomized study to compare the success rate, time
      spent performing the blocks, onset time of surgical anesthesia, presence of
      complete motor blockade, and lidocaine plasma concentrations between conventional
      axillary block and a new approach at the midhumeral level. Both techniques were
      performed using a peripheral nerve stimulator. Two nerves were located at the
      axillary crease, whereas four nerves were located at the midhumeral level. Sixty
      patients undergoing upper limb surgery were assigned to one of the two
      techniques. The sensory block was evaluated before surgery for all of the
      distributions of the four major nerves of the upper extremity. A subset of
      patients had lidocaine plasma concentrations determined. Times to perform the
      blocks, mean maximum plasma lidocaine concentration, and time to peak
      concentration were not different between groups. The success rate of the block,
      as well as the incidence of complete motor blockade, was greater with the
      midhumeral approach compared with the axillary approach. However, the onset time
      to complete anesthesia of the upper extremity was shorter in the axillary
      approach. For brachial plexus anesthesia, we conclude that the midhumeral
      approach provided a greater success rate than the traditional axillary approach.

PMID- 9141933
TI  - Quantitative assessment of differential sensory blockade after lumbar epidural
      lidocaine.
AB  - A cutaneous current perception threshold (CPT) sensory testing device measures
      both large and small diameter sensory nerve fiber function and may be useful in
      evaluating differential neural blockade. Eight subjects received both lumbar
      epidural saline and lumbar epidural lidocaine. Five milliliters of normal saline
      was administered and the CPTs were measured. After the saline, 10 mL of 2% plain
      lidocaine was administered. CPTs, and sensation to touch, pinprick, and cold were
      subsequently measured. Saline had no effect on any measurements. Lidocaine caused
      an increase in all CPTs at the umbilicus and the knee reaching a statistical
      significance at 5 Hz for the umbilicus only. The great toe showed a slight
      increase of the 5 Hz stimulus and no increase of the 2000 or 250 Hz stimulus.
      There was a significant decrease in touch, pinprick, and cold sensation at the
      umbilicus and knee and a significant decrease in the cold sensation at the great
      toe. There was no effect on any measurements made at the mastoid. Epidural
      lidocaine resulted in a differential neural blockade as measured by a CPT monitor
      but not with crude sensory measurements.

PMID- 9141932
TI  - Neurologic complications of 603 consecutive continuous spinal anesthetics using
      macrocatheter and microcatheter techniques. Perioperative Outcomes Group.
AB  - Recent case reports of cauda equina syndrome after continuous spinal anesthesia
      have led to a reevaluation of the indications and applications of this regional
      anesthetic technique. However, few large studies have formally investigated the
      frequency of neurologic complications using macro- and microcatheter (smaller
      than 24 gauge) techniques. This retrospective review examines 603 continuous
      spinal anesthetics, including 127 administered through a 28-gauge microcatheter,
      performed between June 1987 and May 1992. The surgical procedure was orthopedic
      in 397 of 476 (83.4%) macrocatheter patients. All microcatheter patients were
      parturients. Three patients reported pain (persistent paresthesia)
      postoperatively. In two patients, the symptoms resolved in 4 days; the other
      patient was discharged 8 days postoperatively with residual foot pain. There was
      also one patient with aseptic meningitis and one patient with a sensory cauda
      equina syndrome (still present after 15 mo). There were 58 (9.6%) patients with a
      postdural puncture headache (PDPH), including 42 of 127 (33.1%) patients in the
      microcatheter group. An epidural blood patch was performed in 41 (6.8%) patients.
      The frequency of neurologic complications, excluding PDPH, is similar to those in
      published reviews. However, PDPH in microcatheter patients is more frequent than
      previously reported.

PMID- 9141934
TI  - Alteration of renal blood flow during epidural anesthesia in normal subjects.
AB  - The cardiovascular consequences of epidural anesthesia secondary to sympathetic
      blockade are well documented; however, their repercussions on renal hemodynamics
      in humans have not been reported. We investigated the effect of epidural
      anesthesia on renal blood flow (RBF) in 13 healthy volunteers 18-45 yr of age.
      RBF was measured using paraaminohippurate clearance before and after bilateral T6
      epidural sensory block (to ensure adequate sympathetic renal nerve blockade).
      Epidural anesthesia was established using 22 +/- 3 mL of 2% plain lidocaine
      (without epinephrine) via L1-L2 epidural catheter; urine output was measured
      using a three-way Foley catheter. Mean arterial pressure remained > or = 70 mm Hg
      in all subjects without any pharmacologic intervention. Mean RBF before epidural
      anesthesia was 16.1 +/- 6.8 mL.kg-1.min-1 and 14.3 +/- 2.9 mL.kg-1.min-1 after
      bilateral T6 epidural blockade. We conclude that the institution of epidural
      anesthesia in healthy subjects does not result in a significant change in RBF (P
      > 0.25).

PMID- 9141935
TI  - Effect on postoperative analgesia of small-dose lysine acetylsalicylate added to
      prilocaine during intravenous regional anesthesia.
AB  - Nonsteroidal antiinflammatory drugs act largely peripherally by blocking the
      local synthesis of prostaglandins. The aim of this study was to evaluate whether
      the addition of a small dose of lysine acetylsalicylate (LA) to the prilocaine
      used for intravenous regional anesthesia (IVRA) would improve the quality of
      postoperative analgesia. Sixty patients undergoing lower extremity IVRA for foot
      or ankle surgery were randomly assigned to three double-blind groups: LA-IVRA
      where 90 mg of LA was mixed with prilocaine 0.5% for IVRA and 1 mL of 0.9% NaCl
      administered intravenously (IV) through the forearm catheter after tourniquet
      inflation; LA-IV where 1 mL of 0.9% NaCl was mixed with prilocaine and 90 mg of
      LA administered IV; and placebo where 1 mL of 0.9% NaCl was administered both
      with prilocaine for the IVRA and IV. Duration of analgesia (time elapsed between
      tourniquet release and first injection of morphine, expressed as mean +/- SD) was
      significantly longer (P < 0.05) in LA-IVRA (387 +/- 216 min) when compared with
      LA-IV (175 +/- 264 min) and placebo (126 +/- 201 min). Analgesic requirements
      remained significantly lower in LA-IVRA when compared with placebo only during
      the first six postoperative hours, LA-IV being in an intermediate position. Pain
      scores were significantly lower in LA-IVRA during the first postoperative hour
      when compared with LA-IV and during the first 3 postoperative hours when compared
      with placebo. We conclude that 90 mg of LA (corresponding to 50 mg of
      acetylsalicylic acid) added to prilocaine 0.5% during IVRA improves the quality
      of postoperative analgesia in the early postoperative period.

PMID- 9141936
TI  - Preemptive ketamine decreases postoperative narcotic requirements in patients
      undergoing abdominal surgery.
AB  - The aim of this study was to determine if preemptive administration of systemic
      ketamine decreases postoperative pain when compared with postwound closure
      administration of ketamine. Patients undergoing abdominal procedures were
      randomized into a preemptive or postwound closure ketamine administration group.
      Before surgical incision, patients in the preemptive group (n = 20) were given
      0.5 mg/kg ketamine followed by a ketamine infusion of 10 micrograms.kg-1.min-1,
      which was discontinued at abdominal closure. The patients in the postwound
      closure (n = 20) group were given 0.5 mg/kg of ketamine immediately after
      abdominal closure. Postoperatively, all patients received intravenous (IV)
      morphine in the postanesthesia care unit (PACU) and were started on IV morphine
      patient-controlled analgesia after discharge from the PACU. Postoperative pain
      was assessed by measuring morphine consumption and visual analog scale (0-100 mm)
      pain scores at rest. Patients in the preemptive group had significantly lower
      morphine consumption on postoperative Days 1 and 2. No significant intergroup
      differences were seen in the pain scores throughout the study period. Preemptive
      ketamine decreased postoperative opioid requirements, which was observed long
      after the normal expected duration of ketamine.

PMID- 9141937
TI  - The effect of nasal continuous positive airway pressure on plasma endothelin-1
      concentrations in patients with severe cardiogenic pulmonary edema.
AB  - We investigated the effects of nasal continuous positive airway pressure (CPAP)
      on plasma endothelin-1 (ET-1) concentrations in patients with cardiogenic
      pulmonary edema. Thirty patients were randomly assigned to two groups: 15
      patients who received oxygen plus nasal CPAP (CPAP group), and 15 patients who
      received only oxygen by face mask (oxygen group). The heart rate and the mean
      pulmonary artery pressure decreased significantly in the CPAP group. The PaO2/
      fraction of inspired oxygen (FIO2) ratio increased in the CPAP group (163 +/- 70
      to 332 +/- 104, P < 0.01) after 6 h and was significantly higher than that in the
      oxygen group. Arterial plasma ET-1 concentrations decreased from 6.2 +/- 2.0
      pg/mL to 4.8 +/- 1.7 pg/mL (P < 0.05) after 6 h and to 3.3 +/- 0.7 pg/mL (P <
      0.01) after 24 h in the CPAP group. Arterial plasma ET-1 concentrations in the
      CPAP group compared with the oxygen group were significantly lower at 24 h. There
      was a correlation between the arterial plasma ET-1 concentrations and mean
      pulmonary artery pressure (r = 0.62, P < 0.001), and PaO2/FIO2 (r = -0.46, P <
      0.01). Nasal CPAP led to an early decrease in plasma ET-1 concentrations, and
      improvement in oxygenation and hemodynamics.

PMID- 9141938
TI  - ONO-5046, an elastase inhibitor, attenuates endotoxin-induced acute lung injury
      in rabbits.
AB  - Endotoxin causes acute lung injury resembling acute respiratory distress
      syndrome. Elastase, as well as reactive oxygen species released from activated
      neutrophils, are thought to play pivotal roles in the pathogenesis of this lung
      injury. This study investigated whether ONO-5046, a specific elastase inhibitor,
      can attenuate acute lung injury induced by endotoxin in rabbits. Thirty-two male
      anesthetized rabbits were randomly assigned to receive one of four treatments (n
      = 8 for each group): infusion of saline without ONO-5046 treatment (Group S-S),
      infusion of saline with ONO-5046 (Group S-O), infusion of Escherichia coli
      endotoxin (100 micrograms/kg over 60 min) without ONO-5046 (Group E-S), and
      infusion of endotoxin with ONO-5046 (Group E-O). Fifteen minutes before the
      infusion of endotoxin (Groups E-O and E-S) or saline (Groups S-S and S-O), the
      animals received a bolus injection of ONO-5046 (10 mg/kg) followed by continuous
      infusion (10 mg.kg-1.h-1: Groups S-O and E-O) or saline (Groups S-S and E-S). The
      lungs of the rabbits were ventilated with 40% oxygen. Hemodynamics, peripheral
      leukocyte and platelet counts, and PaO2 were recorded during the ventilation
      period (6 h). Lung mechanics, cell fraction of the bronchoalveolar lavage fluid
      (BALF), activated complement, cytokines, and arachidonic acid metabolite
      concentrations in the BALF were measured at 6 h. The wet- to dry (W/D)-weight
      ratio of the lung and albumin concentrations in BALF were analyzed as indices of
      pulmonary edema. Endotoxin decreased lung compliance and PaO2, and increased the
      W/D weight ratio, neutrophil counts, and albumin concentration in the BALF.
      Concentrations of activated complement C5a, interleukin-6, interleukin-8, and
      thromboxane B2 in the BALF were increased by the infusion of endotoxin. ONO-5046
      treatment attenuated these changes. Endotoxin caused extensive morphologic lung
      damage, which was lessened by ONO-5046. In conclusion, intravenous ONO-5046
      pretreatment attenuated endotoxin-induced lung injury in rabbits. This beneficial
      effect of ONO-5046 may be due, in part, to a reduction in the levels of mediators
      that activate neutrophils, in addition to the direct inhibitory effect on
      elastase.

PMID- 9141939
TI  - Thiopental-rocuronium versus ketamine-rocuronium for rapid-sequence intubation in
      parturients undergoing cesarean section.
AB  - We investigated the neuromuscular effects and conditions of tracheal intubation
      after administration of rocuronium in 40 parturients undergoing elective cesarean
      section. After preoxygenation, anesthesia was induced in 20 patients by
      thiopental 4 mg/kg and, in the other 20 patients, by ketamine 1.5 mg/kg.
      Rocuronium 0.6 mg/kg was then administered, and neuromuscular transmission was
      assessed using electromyographic response to train-of-four stimulation of the
      ulnar nerve at the wrist every 10 s. The time to T1/control ratio of 50%
      neuromuscular block (NMB) as well as the time to maximum NMB (onset time) were
      compared in the two groups. The time to 50% block was 45 +/- 10 s in the
      thiopental group and 42 +/- 14 s in the ketamine group, while the onset time was
      105 +/- 35 s in the thiopental group and 101 +/- 35 s in the ketamine group.
      Neither the time to 50% NMB nor the onset time were significantly different
      between the two groups. Tracheal intubation at 50% NMB was easily performed in
      all patients in the ketamine-rocuronium group but was difficult in 75% of the
      thiopental-rocuronium group. We concluded that ketamine 1.5 mg/kg followed by
      rocuronium 0.6 mg/kg may be suitable for rapid-sequence induction of anesthesia
      in parturients undergoing cesarean section.

PMID- 9141940
TI  - Duration of intrathecal labor analgesia: early versus advanced labor.
AB  - Early first-stage labor pain is primarily visceral in origin. Increasing pain
      intensity and transition to somatic nociceptive input characterizes late first-
      and second-stage labor pain. The effect of this change in nociceptive input on
      the duration of intrathecal labor analgesia has not been well studied. This
      prospective cohort observational study compares the duration of intrathecal labor
      analgesia after intrathecal injections made in early labor (3- to 5-cm cervical
      dilation) and those made in more advanced labor (7- to 10-cm cervical dilation).
      Forty-one parturients (18 in early labor and 23 in advanced labor) received
      intrathecal sufentanil (10 micrograms) and bupivacaine (2.5 mg) as part of a
      combined spinal-epidural technique. Patients rated their pain using a 0-10 verbal
      pain scale prior to intrathecal injection and every 20 min thereafter. Duration
      of analgesia was defined as the lesser of time until the pain score exceeded 5 or
      until a request for supplemental epidural analgesia was made. The duration of
      spinal analgesia was significantly less when intrathecal injection was made in
      advanced labor (120 +/- 26 min) compared with early labor (163 +/- 57 min, P <
      0.01). We conclude that cervical dilation and stage of labor significantly impact
      the effective duration of intrathecal sufentanil/ bupivacaine labor analgesia.

PMID- 9141941
TI  - Hemodynamic effects of intravenous isoproterenol versus saline in the parturient.
AB  - The use of epinephrine as a test dose for epidural analgesia in obstetrics
      remains controversial. Isoproterenol as a test dose may be efficacious in the
      parturient. However, the effects of isoproterenol on the uterine blood flow (UBF)
      and umbilical blood flow (UMB) in the parturient are unknown. In a randomized,
      double-blind study, the hemodynamic variables in 60 nonlaboring women at term
      were studied 5 min before and for 10 min after an intravenous injection of either
      5 micrograms isoproterenol or 5 micrograms saline. The UBF was assessed in 35
      women and the UMB in 25 women using a color Doppler technique. The results of 50
      women were used for further analysis. Maternal heart rate (MHR) was measured
      continuously, and maternal mean arterial pressure was measured every minute. MHR
      did not change after saline but increased significantly after injection of
      isoproterenol. UBF also increased significantly after isoproterenol during the
      same time interval. UMB did not change. Other hemodynamic variables did not
      change. We conclude that isoproterenol, 5 micrograms, may be a suitable test dose
      for epidural analgesia in obstetrics.

PMID- 9141942
TI  - Intravenous nitroglycerin to relieve intrapartum fetal distress related to
      uterine hyperactivity: a prospective observational study.
AB  - During a 1-yr period, we evaluated prospectively the use of nitroglycerin (NTG)
      to relieve severe intrapartum fetal distress related to uterine hyperactivity.
      Sixty to ninety micrograms of NTG were injected intravenously (i.v.) within 2-5
      min after onset of severe fetal distress after oxygen administration, left
      lateral decubitus, and discontinuation of any ongoing oxytocin infusion (62%) had
      failed to resolve the fetal heart rate abnormality. A second dose (60 or 90
      micrograms) was used 2-3 min later as required. NTG was completely effective in
      22 cases (fetal distress resolution within 4-5 min with restoration of normal
      uterine activity) and partially but sufficiently effective in the remaining 2
      cases (fetal distress resolution within 4-5 min with residual mild uterine
      hyperactivity). However, a second dose was required for nine parturients (38%).
      Six parturients (25%) developed hypotension 2 min after the first NTG injection,
      with a mean nadir of 93.2 mm Hg (minimum 85 mm Hg). Hypotension was always
      rapidly reversed with a small single dose of ephedrine (4.5-6 mg). In conclusion,
      we found small doses (60-180 micrograms) of IV NTG to be associated with
      resolution of severe fetal distress related to uterine hyperactivity along with
      negligible side effects.

PMID- 9141943
TI  - Prevention of fetal and maternal cyanide toxicity from nitroprusside with
      coinfusion of sodium thiosulfate in gravid ewes.
AB  - Coadministration of sodium thiosulfate with sodium nitroprusside (SNP) to
      children and adults prevents increases in cyanide concentrations during
      anesthesia or long-term SNP infusions. We wondered whether maternally
      administered sodium thiosulfate would prevent increases in fetal red cell cyanide
      concentrations in gravid ewes receiving SNP infusions. Under anesthesia, the
      fetal head was delivered through a lateral hysterotomy for catheterization of the
      jugular vein; the fetus was left in utero. Six control ewes near term received
      SNP at 25 micrograms.kg-1.min-1 for 4 h. Norepinephrine was used to maintain
      maternal mean arterial pressure at 80% baseline values. Six experimental ewes
      received the same treatment except that sodium thiosulfate was infused with SNP
      (1 g sodium thiosulfate per 100 mg SNP). Serial red cell cyanide concentrations
      in ewes and fetuses were followed. One control fetal death resulted from abruptio
      placenta, and this ewe and fetus were excluded from analysis. An additional
      control ewe and fetus died from apparent cyanide poisoning late during the course
      of the experiment. While control ewes and fetuses suffered progressive increases
      in red cell cyanide concentrations into the toxic range, experimental ewes and
      fetuses never developed toxic red cell cyanide levels (ewes P < .003, fetuses P <
      .004). These data, if applicable to humans, suggest that coadministration of
      sodium thiosulfate with SNP to pregnant women at doses currently in use for
      nonpregnant patients will prevent fetal, as well as maternal, cyanide toxicity.

PMID- 9141944
TI  - Propofol is a peroxynitrite scavenger.

PMID- 9141945
TI  - The World Federation of Societies of Anesthesiologists: McMechan's final legacy?

PMID- 9141946
TI  - Spinal epidural hematoma detected by lumbar epidural puncture.

PMID- 9141947
TI  - Epidural fibrin glue injection stops persistent cerebrospinal fluid leak during
      long-term intrathecal catheterization.

PMID- 9141948
TI  - Retrograde fiberoptic intubation.

PMID- 9141949
TI  - The Zavanelli maneuver does not preclude regional anesthesia.

PMID- 9141950
TI  - Severe postadenoidectomy bleeding revealing congenital alpha 2 antiplasmin
      deficiency in a child.

PMID- 9141951
TI  - Anesthetic management of cesarean delivery complicated by ex utero intrapartum
      treatment of the fetus.

PMID- 9141952
TI  - Massive subcutaneous emphysema and severe hypercarbia in a patient during
      endoscopic transcervical parathyroidectomy using carbon dioxide insufflation.

PMID- 9141953
TI  - Massive pulmonary edema in a habitual crack cocaine smoker not chemically
      positive for cocaine at the time of surgery.

PMID- 9141954
TI  - Cardiopulmonary bypass in a patient with moyamoya disease.

PMID- 9141955
TI  - The utility of intravascular ultrasound in evaluating pulmonary artery
      anastomosis in a lung transplantation swine model.

PMID- 9141956
TI  - Effects of ThermH2Osorb carbon dioxide absorber on temperature and humidity in
      the anesthetic circuit.

PMID- 9141957
TI  - Isobaric spinal anesthesia for lumbar disk surgery.

PMID- 9141958
TI  - Usefulness of transesophageal echocardiography in the diagnosis and surgical
      management of a paradoxical embolus extending through a patent foramen ovale.

PMID- 9141959
TI  - A simple system to prevent epidural catheter hub disconnections.

PMID- 9141960
TI  - Anesthesia patient information on the World Wide Web.

PMID- 9141961
TI  - Local analgesia effect of nonsteroidal antiinflammatory drugs.

PMID- 9141962
TI  - Criticism of Hartung's analysis.

PMID- 9141963
TI  - Annual scientific meeting of the British Society for Haematology. Harrogate,
      United Kingdom, 14-17 April 1997. Abstracts.

PMID- 9141964
TI  - Antiplatelet therapy alone is safe and effective after coronary stenting:
      observations of a transition in practice.
AB  - OBJECTIVE: To evaluate the safety and efficacy of transition in practice after
      coronary stenting to antiplatelet therapy alone compared with anticoagulation
      with warfarin. DESIGN: Retrospective analysis of coronary stent management in a
      tertiary Canadian centre. PATIENTS: A total of 136 consecutive patients (146
      lesions) were analyzed who underwent Palmaz-Schatz coronary stenting over a 15
      month period and were treated with anticoagulation with warfarin (56 patients) or
      antiplatelet therapy alone with ticlopidine and acetylsalicylic acid (80
      patients) during the transition in poststenting therapy in the authors' practice.
      Treatment was continued for 30 days in both groups. High pressure stent
      deployment was used in the majority of cases (greater than 90%), and use of
      intravascular ultrasound was infrequent (less than 12%). MAIN RESULTS: At 30
      days, there were no clinical manifestations of stent thrombosis, coronary artery
      bypass surgery or repeat angioplasty in either group. One death occurred in the
      antiplatelet group. Periprocedural non-Q wave myocardial infarction occurred in
      two patients in the antiplatelet group and in one patient in the warfarin group.
      There was a significantly higher incidence of vascular complications in the
      warfarin group than in the antiplatelet group (14.3% versus 2.5%, respectively, P
      = 0.04). The length of hospital stay was significantly shorter in the
      antiplatelet group than in the warfarin group (3.0 +/- 1.8 versus 6.7 +/- 2.6
      days, respectively, P < 0.001). CONCLUSIONS: Reduced anticoagulation with
      antiplatelet therapy alone after coronary stenting, despite infrequent use of
      intravascular ultrasound, is an effective and safe strategy with a low rate of
      vascular complications, a relatively short hospital stay and a low incidence of
      clinical manifestations of stent thrombosis.

PMID- 9141965
TI  - Effects of aortic valve replacement on exercise duration and functional status in
      adults with valvular aortic stenosis.
AB  - OBJECTIVE: To evaluate the effect of aortic valve replacement on left ventricular
      function, functional status and exercise duration in an adult population with
      valvular aortic stenosis. DESIGN: Prospective study of initially asymptomatic
      patients with pre- and postvalve replacement echocardiography, functional status
      score and exercise data. SETTING: University-affiliated, tertiary care teaching
      hospital. PATIENTS: Valvular aortic stenosis patients referred from academic and
      private practice internists and cardiologists (n = 34, 65% men, mean age 68 +/-
      11 years, preoperative aortic valve area 0.9 +/- 0.4 cm2). INTERVENTIONS: Annual
      Doppler echocardiography, functional status questionnaires and, if possible,
      Bruce protocol maximal exercise tolerance tests. MAIN RESULTS: Aortic valve
      replacement resulted in a decrease in maximum jet velocity (pre 4.7 +/- 0.7
      versus post 2.9 +/- 0.7 m/s, P = 0.0001) and left ventricular mass (pre 167 +/-
      37 versus post 134 +/- 32 g, P = 0.0001) and an increase in left ventricular
      ejection fraction (pre 65 +/- 11 versus post 69 +/- 10%, P = 0.05) at rest.
      However, there was no change in the ratio of early to atrial diastolic filling
      velocities (pre 1.2 +/- 0.5 versus post 1.4 +/- 0.8, not significant), exercise
      tolerance as assessed by estimated functional aerobic impairment (pre 26 +/- 32
      versus post 22 +/- 27%, not significant) or functional status score (pre 89 +/-
      13 versus post 91 +/- 11, not significant). CONCLUSIONS: When the aortic valve is
      replaced promptly at symptom onset, despite improvement in resting left
      ventricular systolic performance, there is no evidence of improvement in exercise
      capacity or functional status.

PMID- 9141966
TI  - Towards improved coding of acute myocardial infarction in hospital discharge
      abstracts: a pilot project.
AB  - OBJECTIVE: To pilot-test a simple checklist designed to improve coding of acute
      myocardial infarction (AMI) in hospital discharge abstracts. BACKGROUND: Health
      records technologists review hospital charts to code discharge diagnoses
      according to the International Classification of Diseases, 9th revision (ICD-9).
      Many studies have suggested that there is a high false positive rate in coding
      AMI, ie, ICD-9 410, on hospital discharge abstracts. PATIENTS AND METHODS: The
      checklist required either at least two of suggestive symptoms, diagnostic
      electrocardiographic changes, or diagnostic rise in serum cardiac enzymes; or
      confirmation by autopsy. First case of use was confirmed-typical time to complete
      the checklist was 3 to 4 mins. Then 16 Ontario community hospitals were recruited
      to apply the checklist on a blinded basis to 1000 randomly drawn in-patient
      records-10% were audited for another study to confirm AMI; and 90% were
      originally coded with 'most responsible diagnosis' (MRD) of AMI, other
      cardiovascular diagnoses and various noncardiac conditions. Percentage agreement
      (95% CI) between the checklist and the confirmed or coded diagnosis was analyzed;
      coding of AMI as a secondary diagnosis was examined in further analyses. RESULTS:
      One hospital withdrew for logistical reasons; the final useable sample from 15
      hospitals was 943 records. The checklist correctly identified 100% of AMIs
      independently confirmed for another study; usual coding identified 89.7% of cases
      (70 of 78; 95% CI 80.8 to 95.5). For cases not confirmed, but where the physician
      had nonetheless diagnosed AMI, six of 11 charts were miscoded as AMI in hospital
      records; none were miscoded by the checklist. For records with AMI as MRD, 11.6%
      (44 of 380; 95% CI 8.5 to 15.2) were classified as false positives by the
      checklist. Where an AMI was coded as a secondary diagnosis, 52.9% (36 of 68; 95%
      CI 40.5 to 65.2) met the checklist criteria for AMI. Finally, among records where
      the MRD was other than AMI, 6.8% (38 of 563; 95% CI 4.8 to 9.2) met checklist
      criteria for AMI during admission, but 94.7% had an ICD-9410 code as a secondary
      diagnosis. CONCLUSION: A simple checklist can be very easily applied, has
      extremely high sensitivity for confirming the presence of AMI, and identifies a
      clinically significant proportion of charts with false positive codes for AMI.
      Conversely, these findings support the high sensitivity (low false negative
      rates) of conventional coding practices for AMI in Canadian hospital records, be
      it as a primary or secondary diagnosis (eg, 95% detection rate). Usual coding,
      combined with the checklist for tentative ICD-9 410 diagnoses, would improve the
      accuracy of Canadian hospital records.

PMID- 9141967
TI  - Utility of full electrophysiological study before accessory pathway ablation in
      Wolff-Parkinson-White syndrome.
AB  - BACKGROUND: A single catheter technique has been described for ablation in
      patients with Wolff-Parkinson-White syndrome. It is unknown how often omission of
      a standard electrophysiological study would lead to misdiagnosis based on an
      assumption that the manifest accessory pathway is responsible for clinical
      tachycardia. OBJECTIVES: To examine the contribution of the standard
      electrophysiological study versus an abbreviated, single catheter approach in
      patients with Wolff-Parkinson-White syndrome and an overt delta wave
      electrocardiographically. PATIENTS AND METHODS: One hundred and fifty consecutive
      patients with a delta wave present on electrocardiogram referred for ablation had
      prior full diagnostic electrophysiological study. RESULTS: In 83% (124 of 150) of
      patients, the index accessory pathway was responsible for tachycardia and single
      catheter ablation would suffice. In 11% (17 of 150) of patients, the index
      pathway was not found to be the culprit producing tachycardia and in another 6%
      (nine of 150) additional information was obtained from electrophysiological study
      with possible clinical significance. CONCLUSIONS: Omission of the full diagnostic
      electrophysiological study is acceptable in the majority of patients presenting
      with a delta wave on electrocardiogram. However, important clinical information
      is missed in a sizeable minority of patients.

PMID- 9141969
TI  - Increased oxysterol contents in diabetic rat hearts: their involvement in
      diabetic cardiomyopathy.
AB  - BACKGROUND: Abnormal lipid metabolism associated with diabetes mellitus has been
      proposed to be involved in the pathogenesis of diabetic cardiomyopathy.
      Oxysterols, oxidation derivatives of cholesterol, are known to be highly
      cytotoxic. OBJECTIVE: To monitor changes in myocardial oxysterols and to assess
      the effect of probucol, a lipid lowering agent, on myocardial lipids and
      oxysterols in diabetic rats. METHODS AND RESULTS: Streptozotocin-induced diabetic
      rats were divided into two groups; one group was put on a standard diet, and the
      other a diet containing 1% (weight/weight) probucol for eight weeks. Two
      oxysterols, 7 beta-hydroxycholesterol and 7-ketocholesterol, were identified in
      myocardium by capillary gas chromatography. Both 7 beta-hydroxycholesterol and 7
      ketocholesterol were significantly increased in diabetic rats (49.9 +/- 9.4 ng/mg
      dry weight versus 5.8 +/- 1.2 in controls, P < 0.05; and 5.3 +/- 1.2 ng/mg dry
      weight versus 1.7 +/- 0.1 in controls, P < 0.01, respectively). Probucol reduced
      not only plasma lipids but also myocardial lipids except for cholesterol and
      sphingomyelin fractions. However, probucol did not improve insulin deficiency,
      glucose metabolism or myocardial oxysterol contents. CONCLUSIONS: This study
      demonstrated an increase in oxysterols in the myocardium of diabetic rats,
      suggesting that oxysterols may play a role in the development of diabetic
      cardiomyopathy. Probucol did not decrease the myocardial oxysterol content at the
      dose used in this study, suggesting that the increase in oxysterols may not be
      attributed to high circulating concentrations of lipids, but rather to disturbed
      myocardial metabolism due to insulin deficiency.

PMID- 9141968
TI  - Quantitative relation of electrocardiographic and angiocardiographic measures of
      risk in patients with coronary atherosclerosis. Simvastatin/Enalapril Coronary
      Atherosclerosis Trial (SCAT) Investigators.
AB  - OBJECTIVE: To correlate angiocardiographic and electrocardiographic (ECG)
      measures of risk in coronary artery disease (CAD) patients. SETTING: Baseline
      substudy of the Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT), a 2
      x 2 factorial, randomized, controlled trial of CAD regression. PATIENTS: One
      hundred and twenty-three CAD patients, 113 males and 10 females; average age, 59
      years. METHODS: Bivariate correlations of multiple quantitative measures of
      epicardial coronary angiographic luminal narrowing (quantitative coronary
      angiography [QCA]) and body surface ECG maps of the sum of the decrease in the
      potential time integral of the ST segment (SST decrease) between rest and symptom
      limited exercise and between rest and 1 and 5 mins postexercise recovery.
      RESULTS: The average number of epicardial coronary segments analyzed per patient
      was 12. The mean diameter averaged 2.78 mm; the minimal diameter, 2.01 mm. The
      mean percentage coronary stenosis averaged 29.6% and the most severe averaged
      62.9%. sigma ST decrease averaged -5323 microV.s between rest and peak exercise
      and recovered slowly, averaging -5117 microV.s at 1 min postexercise and -4562
      microV.s at 5 mins. No QCA measure correlated with any ECG variable (range of r,
      0.002 to -0.179; not significant). CONCLUSIONS: Among CAD patients there are no
      close, or causal, relations between angiographic measures of anatomic epicardial
      coronary atherosclerosis and ECG functional measures of exercise-induced
      myocardial ischemia. These data suggest that demonstrated values of stress ECG
      and coronary angiography for the prediction of clinical risk in CAD patients are
      largely independent of each other.

PMID- 9141970
TI  - Torsade de pointes with amiodarone in a patient with previous torsade during beta
      receptor blockade.
AB  - Torsade de pointes is a potentially lethal ventricular arrhythmia that is
      associated with prolonged QT intervals and is often caused by drugs that prolong
      repolarization. Among the most common drugs that may cause torsade de pointes are
      antiarrhythmic drugs including quinidine, procainamide, sotalol and newer class
      III antiarrhythmic agents. The incidence of torsade de pointes associated with
      amiodarone, however, is reported to be much lower. A case is reported of
      amiodarone-induced torsade de pointes following the development of the same
      arrhythmia during beta-blocker use. This case illustrates that although the
      reported incidence of torsade de pointes during amiodarone therapy is low,
      patients with bradycardia-induced torsade de pointes may be a subgroup of
      patients who are at increased risk of this arrhythmia with amiodarone.

PMID- 9141971
TI  - Right outflow tract obstruction by a pedunculated neurofibroma: case report and
      literature review.
AB  - Right outflow tract obstruction due to neurofibroma is rare, with only four cases
      identified in the world literature. Obstruction due to a pedunculated
      neurofibroma has never been reported. A 36-year-old woman with no known heart
      disease presenting with dyspnea, palpitations and chest pain was shown on
      echocardiogram to have a mobile right ventricular mass. Cardiac catheterization
      revealed normal coronary arteries and right ventricular outflow tract obstruction
      by a pedunculated mass, which was surgically removed and histologically proven to
      be a benign neurofibroma. Following surgery the patient's symptoms disappeared,
      with no recurrence three years postoperatively.

PMID- 9141972
TI  - Reversible severe hereditary hemochromatotic cardiomyopathy.
AB  - Two cases of severe hereditary hemochromatotic cardiomyopathy are reported. Both
      patients responded remarkably well to treatment and are leading a normal life
      requiring no cardiac medications, following small volume phlebotomies for two
      years combined, in the first three and six months of treatment, with subcutaneous
      deferoxamine mesylate.

PMID- 9141973
TI  - Right heart pulmonary embolism in transit: a review of therapeutic
      considerations.
AB  - Two patients with pulmonary emboli and right heart masses detected on
      echocardiography are described. One patient underwent successful surgical
      embolectomy and the other was successfully treated with intravenous thrombolysis.
      Both were alive and well at six months' follow-up. The presence of a right heart
      clot in the setting of pulmonary emboli carries a very high mortality rate and
      warrants urgent therapy, which may include anticoagulation, thrombolysis or
      surgical embolectomy. Because limited information is available, therapy must be
      individualized based on patient characteristics, clot location and local
      expertise. The pertinent literature is reviewed and relevant issues in decision
      making are discussed.

PMID- 9141974
TI  - Radiofrequency ablation of bundle branch reentrant tachycardia in a patient with
      atrial septal defect.
AB  - A 22-year-old woman with an atrial septal defect surgically corrected during
      childhood presented with a wide QRS complex tachycardia with left bundle branch
      block morphology. Electrophysiological study was performed and bundle branch
      reentrant tachycardia was induced with morphology identical to clinical
      tachycardia. Radiofrequency catheter ablation of the right bundle branch was
      successful, resulting in complete right bundle branch block and cure of her
      ventricular arrhythmia.

PMID- 9141975
TI  - Informed consent needed before HIV testing of pregnant mothers: CMA.

PMID- 9141976
TI  - Line extension.

PMID- 9141977
TI  - Line extension.

PMID- 9141978
TI  - Touched and troubled by Amy.

PMID- 9141979
TI  - Touched and troubled by Amy.

PMID- 9141980
TI  - The CPP and mental disabilities.

PMID- 9141981
TI  - Radical choices in mastectomy.

PMID- 9141982
TI  - First-line treatment of seasonal (ragweed) rhinoconjunctivitis. A randomized
      management trial comparing a nasal steroid spray and a nonsedating antihistamine.
AB  - OBJECTIVE: To determine whether better health-related quality of life (HRQL) is
      achieved by initiating treatment of seasonal (ragweed) rhinoconjunctivitis (hay
      fever) with a nasal steroid (fluticasone) backed up by a nonsedating
      antihistamine (terfenadine) or whether it is better to start with the
      antihistamine and add the nasal steroid when necessary. DESIGN: Randomized,
      nonblind, parallel-group management study during the 6 weeks of the ragweed
      pollen season in 1995. PATIENTS: Sixty-one adults with ragweed pollen hay fever
      recruited from patients who had participated in previous clinical studies and
      from those who responded to notices in the local media. SETTING: Southern
      Ontario. INTERVENTIONS: Nasal steroid group: 200 micrograms of fluticasone nasal
      spray when needed (up to 400 micrograms/d) starting about 1 week before the
      ragweed pollen season and continued throughout, with 1 to 2 tablets of
      terfenadine daily (maximum 120 mg/d) if needed. Antihistamine group: 1 60-mg
      tablet of terfenadine when needed (maximum 120 mg/d) starting about 1 week before
      the ragweed pollen season and continued throughout, with 200-400 micrograms/d of
      fluticasone nasal spray (maximum 400 micrograms/d) if needed. OUTCOME MEASURES:
      HRQL before, at the height of and toward the end of the ragweed pollen season;
      HRQL was measured using the Rhinoconjunctivitis Quality of Life Questionnaire.
      RESULTS: Overall, HRQL tended to be better in the group of patients whose first
      line treatment was with fluticasone (p = 0.052), but the difference between the 2
      groups was small and not clinically important. Just over half (52% [16/31]) of
      the patients in the fluticasone group did not need additional help with
      terfenadine, whereas only 13% (4/30) of those in the terfenadine group did not
      need additional help with fluticasone (p = 0.002). CONCLUSIONS: There is little
      difference in the therapeutic benefit between the 2 approaches for the treatment
      of ragweed pollen hay fever. Therefore, the approach to treatment should be based
      on patient preference, convenience and cost. Regardless of the treatment, at
      least 50% of patients will need to take both types of medication in combination
      to control symptoms adequately.

PMID- 9141983
TI  - Suicide among Manitoba's aboriginal people, 1988 to 1994.
AB  - OBJECTIVE: To compare and contrast the characteristics of suicides among
      aboriginal and nonaboriginal people in Manitoba. DESIGN: Retrospective review of
      all suicides, based on a confidential analysis of records held by the Office of
      the Chief Medical Examiner. SETTING: Manitoba between 1988 and 1994. OUTCOME
      MEASURES: Standardized suicide rates, age- and sex-specific suicide rates, blood
      alcohol level at time of death, psychiatric help-seeking behaviour before suicide
      and residence on a reserve. RESULTS: Age-standardized suicide rates were 31.8 and
      13.6 per 100,000 population per year among aboriginal and nonaboriginal people,
      respectively. The mean age of aboriginal people who committed suicide was 27.0
      (standard deviation [SD] 10.8) years, compared with a mean age of 44.6 (SD 18.8)
      years for nonaboriginal people who committed suicide (p < 0.001). Blood alcohol
      levels at the time of death were a mean of 28 (SD 23) mmol/L among aboriginal
      people and 12 (SD 20) mmol/L among nonaboriginal people (p < 0.0001). Before
      their death, 21.9% of nonaboriginal suicide victims had sought psychiatric care
      whereas among aboriginal suicide victims 6.6% had sought care (p < 0.0001).
      Although the suicide rate was higher among aboriginal people living on reserve
      than among those living off reserve (52.9 v. 31.3 per 100,000 per year), both of
      these rates were substantially higher than the overall rates among nonaboriginal
      people. There were no significant differences in mean age, sex, blood alcohol
      level and previous psychiatric care among aboriginal people who committed suicide
      living on and off reserve. CONCLUSIONS: There was a high rate of suicide among
      Manitoba's aboriginal people between 1988 and 1994; this rate was comparable to
      earlier estimates of national suicide rates among aboriginal people. The reserve
      environment does not, by itself, account for the high suicide rate among
      Manitoba's aboriginal people. Further study of help-seeking behaviour and the
      association between alcohol abuse and suicide, particularly among aboriginal
      peoples, is indicated.

PMID- 9141984
TI  - First-line treatment of hay fever: what is the best option?

PMID- 9141985
TI  - Bronchiolitis obliterans and wood-burning stoves.

PMID- 9141986
TI  - A sheep named Dolly.

PMID- 9141987
TI  - Bioethics for clinicians: 10. Research ethics.
AB  - Medical research involving human subjects raises complex ethical, legal and
      social issues. Investigators sometimes find that their obligations with respect
      to a research project come into conflict with their obligations to individual
      patients. The ethical conduct of research rests on 3 guiding principles: respect
      for persons, beneficience, and justice. Respect for persons underlies the duty to
      obtain informed consent from study participants. Beneficence demands a favourable
      balance between the potential benefits and harms of participation. Justice
      requires that vulnerable people not be exploited and that eligible candidates who
      may benefit from participation not be excluded without good cause. Studies must
      be designed in a way that ensures the validity of findings and must address
      questions of sufficient importance to justify the risks of participation. In any
      clinical trial there must be genuine uncertainty as to which treatment arm offers
      the most benefit, and placebo controls should not be used if effective standard
      therapies exist. Researchers have a responsibility to inform themselves about the
      ethical, legal and policy standards that govern their activities. When
      difficulties arise, they should consult the existing literature and seek the
      advice of experts in research ethics.

PMID- 9141988
TI  - Teaching medical students how to break bad news.
AB  - PROGRAM OBJECTIVE: To teach medical students to break bad news to patients and
      their families empathically and competently. SETTING: Seven teaching hospitals
      affiliated with the University of Toronto since 1987. PARTICIPANTS: All medical
      students in their third preclinical year. PROGRAM: The course presents a 6-point
      protocol to guide students in breaking bad news and comprises 2 half-day (3-hour)
      teaching sessions. Each session incorporates a video presentation, a discussion
      period and small-group teaching, consisting of exercises followed by 4 different
      role-playing scenarios conducted with the use of standardized patients. The
      course was evaluated through 2 questionnaires, 1 administered before and 1 after
      the course, which measured changes in the students' attitude and strategy.
      Questionnaires were administered during 5 of the years since the course was
      started. A total of 914 precourse and 503 postcourse questionnaires were
      completed, of which 359 matched pairs of precourse and postcourse questionnaires
      were analysed to study any changes due to the course. OUTCOMES: Precourse
      questionnaires showed that 68% of the students had thought about the task of
      breaking bad news often or very often. Of the 56% of students who had seen
      clinicians performing this task, 75% felt that they had seen good examples. The
      proportion of the students who had a plan for how to conduct such an interview
      rose from 49% before the course to 92% after it, and the proportion who felt they
      might be reasonably competent in breaking bad news rose from 23% before the
      course to 74% after it. CONCLUSIONS: The subject of breaking bad news is
      important to medical students, and it is practicable to design a course to teach
      the basic techniques involved. Most students perceive such a course as enjoyable
      and useful and find that it increases their sense of competence and their ability
      to formulate a strategy for such situations.

PMID- 9141989
TI  - Fatal falciparum malaria in Canadian travellers.
AB  - The authors report 2 cases of severe falciparum malaria in Canadians that had
      fatal outcomes. In the first case a man presented to a local hospital shortly
      after returning from Africa, but a diagnosis of malaria was not considered. He
      was transferred to a secondary and then to a tertiary care facility, where he
      subsequently died. Intravenous quinidine therapy, the treatment of choice, was
      unavailable at all 3 hospitals. In the second case, a woman taking chloroquine
      prophylaxis while visiting Nigeria developed cerebral malaria and died. These
      cases illustrate critical management issues: appropriate advice on malaria
      prevention before departure; consideration of malaria in all febrile people
      returning from an endemic area; ready access to parenteral therapy for severe
      malaria in Canadian hospitals; and an increase in awareness of travel medicine
      among family physicians.

PMID- 9141990
TI  - Bronchiolitis obliterans in a man who used his wood-burning stove to burn
      synthetic construction materials.
AB  - Many people heat their homes with wood-burning stoves. However, toxic fire
      effluent can escape from old or improperly operated stoves. The authors describe
      a case in which bronchiolitis obliterans developed in a man within hours after he
      burned synthetic construction materials in his wood-burning stove. Certain
      factors, such as careless or improper use of the stove, the size of the room, the
      lack of open-air ventilation and the composition of the materials burned,
      strongly point to inhalation of the fire effluent as the cause.

PMID- 9141991
TI  - Medical education must make room for student-specific ethical dilemmas.
AB  - Most contemporary undergraduate courses in medical ethics leave a critical gap
      unfilled because they fail to address student-specific issues, says third-year
      student Joye St. Onge. In this article, which won third prize in CMAJs 1996 Dr.
      William Logie Medical Ethics Essay Contest, St. Onge outlines the importance of
      discussing student-specific ethical dilemmas and suggests ways to introduce such
      teaching in medical schools.

PMID- 9141992
TI  - "If you think it hurts now...".

PMID- 9141994
TI  - Negative health care environment weighing on residents, survey reveals.

PMID- 9141993
TI  - Anger over HIV questions cancels blood clinic at Ottawa university.
AB  - Ottawa's Carleton University cancelled a February blood-donor clinic after the
      Red Cross failed to hold sensitivity-training sessions for its volunteers. The
      sessions were requested after students complained that the organization's
      screening procedures are insensitive and offend gay students. The Red Cross
      maintains that rigorous screening, including questions about high-risk sexual
      behaviour, is essential if the blood supply is to be protected. In March a
      compromise was announced: the Red Cross will begin sensitivity training for its
      volunteer workers in April and blood-donor clinics will return to Carleton in the
      fall.

PMID- 9141995
TI  - Storm of protest greets motion to restrict specialty exams.
AB  - A motion by the Royal College of Physicians and Surgeons of Canada to restrict
      specialty examinations to Canadian- and US-trained physicians has met a storm of
      protest from provinces facing acute physician shortages in remote areas. The
      motion was called a "recipe for disaster" for provinces such as Saskatchewan,
      Manitoba and Newfoundland that traditionally have recruited specialists from
      Commonwealth countries to fill positions. The protests prompted the college to
      postpone action on its motion until June.

PMID- 9141996
TI  - Medicare, Medicaid fraud a billion-dollar art form in the US.
AB  - Medicare and Medicaid fraud costs billions of dollars each year in the US.
      Investigators have shown that fraud is found in all segments of the health care
      system. Even though the Canadian system has stricter regulations and tighter
      controls, can regulators here afford to be complacent about believing that such
      abuse would not happen here? One province has established an antifraud unit to
      monitor its health insurance scheme; it already has 1 prosecution under its belt.

PMID- 9141997
TI  - What can the Internet do for me?

PMID- 9141998
TI  - Timing of valve replacement in aortic stenosis. Moving closer to perfection.

PMID- 9141999
TI  - Identifying the predictors of restenosis. Do we need new glasses?

PMID- 9142000
TI  - Correlation between left ventricular hypertrophy and GAA trinucleotide repeat
      length in Friedreich's ataxia.
AB  - BACKGROUND: Friedreich's ataxia (FA), the most common inherited ataxia, is
      associated frequently with cardiac hypertrophy, and death is often cardiac
      related. Recently, the disease has been associated with a mutation that consists
      of an unstable expansion of GAA repeats in the first intron of the gene encoding
      frataxin on chromosome 9. METHODS AND RESULTS: We studied 44 consecutive patients
      with FA, determined the size of GAA expansions in the frataxin gene, and examined
      the relation between the genotype and cardiac phenotype assessed by M-mode and
      two-dimensional echocardiography. All the patients were homozygous for the
      mutation. The size of the GAA expansion on the smaller allele varied from 270 to
      1200. We found a correlation between the size of GAA expansion and the left
      ventricular wall thickness (r = .51, P < .001) and the left ventricular mass
      index (r = .45, P = .002). Left ventricular hypertrophy was observed in 81% of
      patients with a number of GAA repeats above the median value of 770 compared with
      only 14% in the other group (P = .002). CONCLUSIONS: These data demonstrate that
      in FA, the severity of left ventricular hypertrophy is related to the number of
      GAA repeats. These results suggest that abnormalities of the gene encoding
      frataxin, a protein of unknown function highly expressed in the normal heart, may
      play an important role in the modulation of cardiac hypertrophy.

PMID- 9142001
TI  - Influence of inhaled nitric oxide on systemic flow and ventricular filling
      pressure in patients receiving mechanical circulatory assistance.
AB  - BACKGROUND: In patients with left ventricular (LV) dysfunction, inhaled nitric
      oxide (NO) decreases pulmonary vascular resistance (PVR) but causes a potentially
      clinically significant increase in left atrial pressure (LAP). This has led to
      the suggestion that inhaled NO may reach the coronary circulation and have a
      negative inotropic effect. This study tested an alternative hypothesis that LAP
      increases because of volume shifts to the pulmonary venous compartment caused by
      NO-induced selective pulmonary vasodilation. METHODS AND RESULTS: The Thermo
      Cardiosystems Heartmate is an LV assist device (LVAD) that can be set (by
      controlling pump rate) to deliver fixed or variable systemic blood flow. Eight
      patients (between 1 and 11 days after LVAD implantation) were administered
      inhaled NO (20 and 40 ppm for 10 minutes), and LAP, systemic flow, and pulmonary
      arterial pressure were measured in both fixed and variable pump flow modes. In
      both modes, inhaled NO lowered PVR (by 25 +/- 6% in the fixed mode, P < .001, and
      by 21 +/- 5% in the variable mode, P < .003). With fixed pump flow, LAP rose from
      12.5 +/- 1.2 to 15.1 +/- 1.4 mm Hg (P < .008). In the variable flow mode, LAP did
      not increase and the assist device output rose from 5.3 +/- 0.3 to 5.7 +/- 0.3
      L/min (P < .008). CONCLUSIONS: A selective reduction in PVR by inhaled NO can
      increase LAP if systemic flow cannot increase. These data support the hypothesis
      that with LV failure, inhaled NO increases LAP by increasing pulmonary venous
      volume and demonstrate that inhaled NO has beneficial hemodynamic effects in LVAD
      patients.

PMID- 9142002
TI  - Prediction of restenosis after coronary balloon angioplasty. Results of PICTURE
      (Post-IntraCoronary Treatment Ultrasound Result Evaluation), a prospective
      multicenter intracoronary ultrasound imaging study.
AB  - BACKGROUND: Intracoronary ultrasound (ICUS) imaging is potentially suitable to
      identify lesions at high risk of restenosis after percutaneous transluminal
      coronary angioplasty (PTCA), but it has not been studied systematically. METHODS
      AND RESULTS: We recruited 200 patients in whom ICUS studies were performed after
      successful PTCA and related their ICUS parameters to 6-month follow-up
      quantitative coronary angiography. This was performed in 164 patients (82%),
      yielding 170 lesions for analysis. The overall incidence of a > or = 50% diameter
      stenosis at follow-up (categorical restenosis) was 29.4%. Quantitative ICUS
      parameters were weakly but significantly related to follow-up minimal luminal
      diameter on quantitative coronary angiography (lumen area: R2 = .36, P = .0001;
      vessel area: R2 = .29, P = .0002; plaque area: R2 = -.18, P = .021; percent
      obstruction: R2 = -.15, P = .05), but categorical restenosis was not
      significantly related to these parameters (P = .63, .77, .38, and .08,
      respectively). There were no significant predictors of restenosis in ICUS
      parameters of plaque morphology: eccentric versus concentric (P = 1.0), plaque
      type (hard, soft, or calcific, P = .98), or the number of calcified quadrants (P
      = .41). There were no significant predictors of restenosis in two predefined
      types of vessel-wall disruptions: (1) rupture: presence (P = .79), depth (partial
      versus complete, P = .85), or extent in quadrants (P = .6), and (2) dissection:
      presence (P = .31), depth (P = .82), or extent (P = .38). CONCLUSIONS:
      Qualitative ICUS parameters after PTCA did not predict restenosis. A larger lumen
      and vessel area and a smaller plaque area by ICUS were associated with a larger
      angiographic minimal lumen diameter at follow-up, but these parameters were not
      significantly related to categorical restenosis.

PMID- 9142003
TI  - Prospective study of asymptomatic valvular aortic stenosis. Clinical,
      echocardiographic, and exercise predictors of outcome.
AB  - BACKGROUND: Only limited data on the rate of hemodynamic progression and
      predictors of outcome in asymptomatic patients with valvular aortic stenosis (AS)
      are available. METHODS AND RESULTS: In 123 adults (mean age, 63 +/- 16 years)
      with asymptomatic AS, annual clinical, echocardiographic, and exercise data were
      obtained prospectively (mean follow-up of 2.5 +/- 1.4 years). Aortic jet velocity
      increased by 0.32 +/- 0.34 m/s per year and mean gradient by 7 +/- 7 mm Hg per
      year; valve area decreased by 0.12 +/- 0.19 cm2 per year. Kaplan-Meier event-free
      survival, with end points defined as death (n = 8) or aortic valve surgery (n =
      48), was 93 +/- 5% at 1 year, 62 +/- 8% at 3 years, and 26 +/- 10% at 5 years.
      Univariate predictors of outcome included baseline jet velocity, mean gradient,
      valve area, and the rate of increase in jet velocity (all P < or = .001) but not
      age, sex, or cause of AS. Those with an end point had a smaller exercise increase
      in valve area, blood pressure, and cardiac output and a greater exercise decrease
      in stroke volume. Multivariate predictors of outcome were jet velocity at
      baseline (P < .0001), the rate of change in jet velocity (P < .0001), and
      functional status score (P = .002). The likelihood of remaining alive without
      valve replacement at 2 years was only 21 +/- 18% for a jet velocity at entry >
      4.0 m/s, compared with 66 +/- 13% for a velocity of 3.0 to 4.0 m/s and 84 +/- 16%
      for a jet velocity < 3.0 m/s (P < .0001). CONCLUSIONS: In adults with
      asymptomatic AS, the rate of hemodynamic progression and clinical outcome are
      predicted by jet velocity, the rate of change in jet velocity, and functional
      status.

PMID- 9142004
TI  - Cold stress provokes sympathoinhibitory presyncope in healthy subjects and
      hemodialysis patients with low cardiac output.
AB  - BACKGROUND: Sudden hypotension in progressive hypovolemia or during hemodialysis
      is attributed to sudden inhibition of sympathetic activity. Critical ventricular
      underfilling seems responsible for this paradox, but it is unknown why the
      transition from sympathoactivation accompanying hypovolemia to sympathoinhibition
      is so abrupt. We studied whether brief fluctuation of sympathetic activity
      induced by cold pressor test (CPT) evokes sympathoinhibition if applied during
      low cardiac output. METHODS AND RESULTS: Fourteen healthy subjects underwent CPT,
      lower-body negative pressure (LBNP; -45 mm Hg for 60 minutes), or the combination
      thereof. CPT alone caused vasoconstriction and increased muscle sympathetic nerve
      activity, followed by uneventful relaxation. When applied during reduced cardiac
      output, tachycardia, and vasoconstriction induced by prior LBNP for 6 minutes,
      CPT again caused vasoconstriction, now followed by acute hypotension in 10
      subjects, and was associated with vasorelaxation, relative bradycardia, and fall
      in muscle sympathetic nerve activity. Eight subjects also experienced acute LBNP
      induced hypotension in the absence of CPT, but not until 17 +/- 6 minutes of
      LBNP. We also performed CPT before and in the final phase of hemodialysis in 8
      patients. Before dialysis, the patients tolerated CPT uneventfully, but during
      hemodialysis, CPT provoked acute hypotension in 5 cases, showing similar
      withdrawal of vasoconstriction. CONCLUSIONS: This is the first study showing that
      brief cold stress, tolerated well in normal circulatory conditions, can provoke
      sudden sympathoinhibition and hypotension when applied during decreased cardiac
      output induced by LBNP or hemodialysis. We suggest that during conditions of a
      decreased cardiac output, subtle sympathetic relaxation such as follows cold
      stress triggers self-enhancing relaxation that cannot be controlled.

PMID- 9142005
TI  - Idiopathic ventricular fibrillation induced with vagal activity in patients
      without obvious heart disease.
AB  - BACKGROUND: Recently, idiopathic ventricular fibrillation (VF) has gained much
      attention. Although several subgroups have been described, its pathogenesis,
      mechanism, treatment, and prognosis remain unknown. METHODS AND RESULTS: We
      studied six cases of idiopathic VF with transient late r' waves and ST elevation
      (late r'/ST elevation) in leads V1 through V3. Late r'/ST elevation was augmented
      before and after VF episodes. Signal-averaged ECGs showed late potentials even
      when no late r'/ST elevation occurred. During late r', a conduction delay was
      observed by use of body-surface maps at the anterior wall and outflow tract of
      the right ventricle without inhomogeneity of the repolarization phase. There was
      a decrease or total disappearance of late r'/ST elevation with isoproterenol,
      atropine, and exercise stress testing and induction or exacerbation with
      propranolol, edrophonium, and hyperventilation. VF was induced by programmed
      electrical stimulation in all cases but two, in which it was induced only after
      edrophonium injection. In two cases, VF was exacerbated by propranolol, and in
      all cases, it was uninducible with isoproterenol. Heart rate spectral analysis
      just before VF episodes showed a sudden rise in vagal activity in two cases. As
      the VF mechanism, a conduction delay exists at the anterior wall and outflow
      tract of the right ventricle that is possibly exacerbated by an abrupt rise in
      vagal activity, inducing random reentry that results in VF. Class I
      antiarrhythmic agents and beta-blockers were ineffective for this VF. All
      subjects required implantable cardioverter-defibrillators. CONCLUSIONS: We
      propose this VF associated with late r'/ST elevation in the precordial leads and
      influenced by vagal activity as a new possible mechanism of idiopathic VF.

PMID- 9142006
TI  - Differential effects of captopril and nitrates on muscle sympathetic nerve
      activity in volunteers.
AB  - BACKGROUND: The sympathetic nervous system (SNS) is an important regulator of
      cardiovascular function. Activation of SNS plays an important role in the
      pathophysiology and the prognosis of cardiovascular diseases such as heart
      failure, acute coronary syndromes, arrhythmia, and possibly hypertension.
      Vasodilators such as adenosine and sodium nitroprusside are known to activate SNS
      via baroreflex mechanisms. Because vasodilators are widely used in the treatment
      of patients with cardiovascular diseases, the aim of the present study was to
      assess the influence of clinically used dosages of isosorbide dinitrate and
      captopril on sympathetic nerve activity at rest and during stimulatory maneuvers.
      METHODS AND RESULTS: Twenty-eight healthy volunteers were included in this double
      blind placebo-controlled study, and muscle sympathetic nerve activity (MSA; with
      microelectrodes in the peroneal nerve), blood pressure, heart rate, and
      neurohumoral parameters were measured before and 90 minutes after the oral
      administration of 40 mg isosorbide dinitrate or 6.25 mg captopril. Furthermore, a
      3-minute mental stress test and a cold pressor test were performed before and 90
      minutes after drug administration. Resting MSA did not change after captopril and
      decreased compared with placebo (P < .05 versus placebo), whereas isosorbide
      dinitrate led to a marked increase in MSA (P < .05). Systolic blood pressure was
      reduced by isosorbide dinitrate (P < .05), whereas captopril decreased diastolic
      blood pressure (P < .05). The increases in MSA, blood pressure, and heart rate
      during mental stress were comparable before and after drug administration
      regardless of the medication. During cold pressor test, MSA and systolic and
      diastolic blood pressures increased to the same degree independent of treatment,
      but after isosorbide dinitrate, the increase in MSA seemed to be less pronounced.
      Heart rate did not change during cold stimulation. Plasma renin activity
      increased after captopril and isosorbide dinitrate (P < .05), whereas placebo had
      no effect. Endothelin-1 increased after placebo and isosorbide dinitrate (P <
      .05) but not after captopril. CONCLUSIONS: Thus, captopril suppressed MSA despite
      lowering of diastolic blood pressure but allowed normal adaptation of the SNS
      during mental or physical stress. In contrast, the nitrate strongly activated the
      SNS under baseline conditions. These findings demonstrate that vasodilators
      differentially interact with the SNS, which could be of importance in therapeutic
      strategies for the treatment of patients with cardiovascular diseases.

PMID- 9142007
TI  - Effects of inhibition of the L-arginine/nitric oxide pathway on vasodilation
      caused by beta-adrenergic agonists in human forearm.
AB  - BACKGROUND: We examined whether vasodilator responses to beta-agonists in human
      forearm vasculature are mediated in part through the nitric oxide pathway.
      METHODS AND RESULTS: We measured forearm blood flow responses to brachial artery
      infusions of beta-adrenergic agonists in healthy men. Salbutamol was more than
      100 times as potent as dobutamine. Cumulative doses of salbutamol (0.3 to 3.5
      nmol.min-1) did not cause tachyphylaxis to an identical repeated infusion after a
      24-minute recovery period. Vasodilators were infused with this sequence during
      coinfusion of saline and NG-monomethyl-L-arginine (L-NMMA, 4 mumol.min-1), an
      inhibitor of nitric oxide synthase. L-NMMA coinfusion inhibited responses (area
      under the dose-response curve) to isoproterenol (0.01 to 0.1 nmol.min-1) by 59 +/
      7% (n = 5) and inhibited those to salbutamol (0.3 to 3.5 nmol.min-1) by 52 +/-
      6% (n = 8). L-NMMA had no significant effect on vasodilator responses to
      nitroprusside (2.7 to 11.0 nmol.min-1, n = 8), verapamil (20 to 80 nmol.min-1, n
      = 8), or prostacyclin (0.08 to 0.24 nmol.min-1, n = 8). CONCLUSIONS: These
      results suggest that beta-adrenergic vasodilator responses in human forearm
      vasculature are mediated predominantly through beta 2-adrenergic receptors and
      are dependent on nitric oxide synthesis.

PMID- 9142008
TI  - Randomized, double-blind, placebo-controlled study evaluating the efficacy and
      safety of AS-013, a prostaglandin E1 prodrug, in patients with intermittent
      claudication.
AB  - BACKGROUND: Intermittent claudication due to peripheral arterial occlusive
      disease (PAOD) is a common cause of pain and disability in the middle-aged.
      Clinical trials of the potent vasodilator prostaglandin E1 have been
      disappointing. This is the first report of a controlled clinical trial of AS-0:3,
      a novel prodrug of prostaglandin E1 incorporated into lipid microspheres that has
      been developed to improve delivery of the active compound to blood vessel walls.
      METHODS AND RESULTS: Eighty patients with stenosis or occlusion, symptoms of
      intermittent claudication, and maximum walking distance of > or = 30 and < or =
      300 m on a standard treadmill test were randomized to placebo or one of three
      dosage regimens of AS-013. Drug was administered by intravenous injection 5 d/wk
      for 4 weeks. Treadmill tests and other assessments were completed at weeks 0, 4,
      and 8. A statistically significant increase in maximum walking distance was
      observed at 4 weeks (for placebo: median, 4.5 m; interquartile range [IQR], 20;
      for active treatment: median, 28.0 m; IQR, 81; P < .01, Mann-Whitney test). A
      similar response was seen at 8 weeks (for placebo; median, -11.2 m; IQR, 35; for
      active treatment: median, 35 m; IQR, 68; P < .01, Mann-Whitney test). Dose
      related improvements in pain-free walking distance and quality of life were
      observed. No serious safety issues were noted. CONCLUSIONS: These promising
      clinical data indicate that AS-013, a new prodrug of prostaglandin E1, could
      provide an effective and acceptable treatment for patients with intermittent
      claudication. Studies to investigate the optimal dosing regimen, duration of
      clinical benefit, and effects in more severe forms of peripheral arterial disease
      are warranted.

PMID- 9142009
TI  - Effects of the nitric oxide donor sodium nitroprusside on intracellular pH and
      contraction in hypertrophied myocytes.
AB  - BACKGROUND: We compared the effects of the nitric oxide donor sodium
      nitroprusside (SNP) on intracellular pH (pHi), intracellular calcium
      concentration ([Ca2+]i) transients, and cell contraction in hypertrophied adult
      ventricular myocytes from aortic-banded rats and age-matched controls. METHODS
      AND RESULTS: pHi was measured in individual myocytes with SNARF-1, and [Ca2+]i
      transients were measured with indo 1 simultaneously with cell motion. Experiments
      were performed at 37 degrees C in myocytes paced at 0.5 Hz in HEPES-buffered
      solution (extracellular pH = 7.40). At baseline, calibrated pHi, diastolic and
      systolic [Ca2+]i values, and the amplitude of cell contraction were similar in
      hypertrophied and control myocytes. Exposure of the control myocytes to 10(-6)
      mol/L SNP caused a decrease in the amplitude of cell contraction (72 +/- 7% of
      baseline, P < .05) that was associated with a decrease in pHi (-0.10 +/- 0.03 U,
      P < .05) with no change in peak systolic [Ca2+]i. In contrast, in the
      hypertrophied myocytes exposure to SNP did not decrease the amplitude of cell
      contraction or cause intracellular acidification (-0.01 +/- 0.01 U, NS). The cGMP
      analogue 8-bromo-cGMP depressed cell shortening and pHi in the control myocytes
      but failed to modify cell contraction or pHi in the hypertrophied cells. To
      examine the effects of SNP on Na(+)-H+ exchange during recovery from
      intracellular acidosis, cells were exposed to a pulse and washout of NH4Cl. SNP
      significantly depressed the rate of recovery from intracellular acidosis in the
      control cells compared with the rate in hypertrophied cells. CONCLUSIONS: SNP and
      8-bromo-cGMP cause a negative inotropic effect and depress the rate of recovery
      from intracellular acidification that is mediated by Na(+)-H+ exchange in normal
      adult rat myocytes. In contrast, SNP and 8-bromo-cGMP do not modify cell
      contraction or pHi in hypertrophied myocytes.

PMID- 9142010
TI  - Decreased myocyte tension development and calcium responsiveness in rat right
      ventricular pressure overload.
AB  - BACKGROUND: The contractile dysfunction observed in end-stage myocardial
      hypertrophy has at its base an abnormality in myocyte function. However, whether
      depressed contractile function is related to an alteration in contractile protein
      function is presently unknown. METHODS AND RESULTS: Contractile force, tension,
      and calcium responsiveness were measured in single-skinned myocytes isolated from
      rats with right ventricular hypertrophy (RVH) and control rats. RVH was induced
      by pulmonary artery constriction for 36 weeks and was associated with significant
      myocyte hypertrophy. Myocytes were attached to micropipettes that extended from a
      force transducer and motor. Isometric force was measured over a wide range of
      calcium concentrations at two sarcomere lengths (SLs). Maximal force was
      increased in the RVH group: 1.20 +/- 0.10 versus 1.62 +/- 0.13 mg at SL = 2.0
      microns and 1.33 +/- 0.10 versus 1.84 +/- 0.15 mg at SL = 2.3 microns (P < .05).
      Maximal tension, however, was reduced in the RVH group: 24.3 +/- 1.91 versus 37.5
      +/- 2.92 mN/mm2 at SL = 2.0 microns and 27.4 +/- 1.78 versus 41.8 +/- 3.19 mN/mm2
      at SL = 2.3 microns (P < .01). The concentration of calcium ions required for
      half-maximal activation was increased in the RVH group: 2.64 +/- 0.13 versus 3.47
      +/- 0.22 mumol/L at SL = 2.0 microns and 2.23 +/- 0.15 versus 2.86 +/- 0.18
      mumol/L at SL = 2.3 microns (P < .01). The slope of the force-calcium
      relationship (Hill coefficient) was decreased in the RVH group at SL = 2.0
      microns (4.3 +/- 0.4 versus 3.1 +/- 0.2, P = .04) but not at SL = 2.3 microns
      (3.8 +/- 0.2 versus 3.6 +/- 0.2, P = NS). CONCLUSIONS: These results suggest that
      the depressed cardiac function of end-stage myocardial hypertrophy may be due, in
      part, to altered contractile protein function.

PMID- 9142011
TI  - Negative inotropic effect of adrenomedullin in isolated adult rabbit cardiac
      ventricular myocytes.
AB  - BACKGROUND: Adrenomedullin (AM) is a potent vasodilator peptide. AM-induced
      vasodilatation is mediated by an increase of NO as well as cAMP. Both AM and
      binding sites for this peptide have been found in cardiac tissue, indicating the
      possible existence of an autocrine or paracrine system of AM in the heart.
      METHODS AND RESULTS: Myocytes were isolated by use of retrograde coronary
      perfusion with physiological solution containing collagenase and hyaluronidase
      from adult rabbit ventricles. Contraction of cardiac myocytes was traced with a
      video motion detector, and [Ca2+]i was measured with indo 1 at 37 degrees C. The
      Ica was measured with a whole-cell patch clamp at 23 degrees C. AM and calcitonin
      gene-related peptide (CGRP), another member of the same peptide family, showed a
      concentration-dependent negative inotropic effect (10(-7) mol/L AM: contraction
      amplitude, 64 +/- 7% of control; [Ca2+]i, 52 +/- 5% of control; n = 10; 10(-6)
      mol/L CGRP: contraction amplitude, 64 +/- 25%; [Ca2+]i, 70 +/- 3%; n = 5; mean +/
      SD). Ica was decreased to 60 +/- 39% by superfusion with AM after the cessation
      of NG-monomethyl-L-arginine (L-NMMA), an NO synthase inhibitor. Pretreatment with
      L-NMMA (10 mumol/L) abolished the negative inotropic effect of AM, whereas
      switching from AM+L-NMMA to AM+L-arginine (1 mmol/L) restored it. Superfusion
      with 8-bromo-cGMP also showed a negative inotropic effect. AM significantly
      increased the intracellular content of cGMP, a second messenger of NO, but not
      that of cAMP. AM (10 nmol/L) blunted the effect of 1 mumol/L forskolin.
      CONCLUSIONS: AM has a negative inotropic effect and decreased both [Ca2+]i and
      Ica, with these effects being at least party mediated via the L-arginine-NO
      pathway in adult rabbit ventricular myocytes.

PMID- 9142012
TI  - Images in cardiovascular medicine. Hydatid cyst of the interventricular septum.

PMID- 9142013
TI  - Images in cardiovascular medicine. Reversible tachycardia-induced cardiomyopathy.

PMID- 9142014
TI  - Guide to primary prevention of cardiovascular diseases. A statement for
      healthcare professionals from the Task Force on Risk Reduction. American Heart
      Association Science Advisory and Coordinating Committee.

PMID- 9142015
TI  - Nutrition and children. A statement for healthcare professionals from the
      Nutrition Committee, American Heart Association.

PMID- 9142016
TI  - Monitoring of peripheral nerve stimulation versus standard clinical assessment
      for dosing of neuromuscular blocking agents.

PMID- 9142017
TI  - Inhaled nitric oxide in adult respiratory distress syndrome: do we know the risks
      versus benefits?

PMID- 9142018
TI  - Blood volume determination using hydroxyethyl starch.

PMID- 9142019
TI  - A randomized, controlled trial of protocol-directed versus physician-directed
      weaning from mechanical ventilation.
AB  - OBJECTIVE: To compare a practice of protocol-directed weaning from mechanical
      ventilation implemented by nurses and respiratory therapists with traditional
      physician-directed weaning. DESIGN: Randomized, controlled trial. SETTING:
      Medical and surgical intensive care units in two university-affiliated teaching
      hospitals. PATIENTS: Patients requiring mechanical ventilation (n = 357).
      INTERVENTIONS: Patients were randomly assigned to receive either protocol
      directed (n = 179) or physician-directed (n = 178) weaning from mechanical
      ventilation. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was the
      duration of mechanical ventilation from tracheal intubation until discontinuation
      of mechanical ventilation. Other outcome measures included need for reintubation,
      length of hospital stay, hospital mortality rate, and hospital costs. The median
      duration of mechanical ventilation was 35 hrs for the protocol-directed group
      (first quartile 15 hrs; third quartile 114 hrs) compared with 44 hrs for the
      physician-directed group (first quartile 21 hrs; third quartile 209 hrs). Kaplan
      Meier analysis demonstrated that patients randomized to protocol-directed weaning
      had significantly shorter durations of mechanical ventilation compared with
      patients randomized to physician-directed weaning (chi 2 = 3.62, p = .057, log
      rank test; chi 2 = 5.12, p = .024, Wilcoxon test). Cox proportional-hazards
      regression analysis, adjusting for other covariates, showed that the rate of
      successful weaning was significantly greater for patients receiving protocol
      directed weaning compared with patients receiving physician-directed weaning
      (risk ratio 1.31; 95% confidence interval 1.15 to 1.50; p = .039). The hospital
      mortality rates for the two treatment groups were similar (protocol-directed
      22.3% vs. physician-directed 23.6%; p = .779). Hospital cost savings for patients
      in the protocol-directed group were $42,960 compared with hospital costs for
      patients in the physician-directed group. CONCLUSION: Protocol-guided weaning of
      mechanical ventilation, as performed by nurses and respiratory therapists, is
      safe and led to extubation more rapidly than physician-directed weaning.

PMID- 9142020
TI  - A prospective, randomized, controlled evaluation of peripheral nerve stimulation
      versus standard clinical dosing of neuromuscular blocking agents in critically
      ill patients.
AB  - OBJECTIVES: To determine if vecuronium doses individualized by peripheral nerve
      stimulation are lower than those doses chosen by standard clinical techniques;
      and to determine whether patients monitored by peripheral nerve stimulation
      exhibit shorter recovery times and less prolonged neuromuscular blockade after
      discontinuation of vecuronium than control patients. DESIGN: A prospective,
      randomized, controlled, single-blind trial. SETTING: Two ten-bed medical
      intensive care units of a 937-bed tertiary care, not-for-profit, teaching
      hospital and health system. PATIENTS: Mechanically ventilated patients requiring
      continuous neuromuscular blockade as part of their therapy. INTERVENTIONS: After
      obtaining written, informed consent and baseline neurologic examinations,
      patients were randomized to treatment, where dosing was individualized by
      peripheral nerve stimulation or standard clinical assessment. Doses in the
      peripheral nerve stimulation group were adjusted to 90% blockade (Train-of-Four
      of 1/4). The standard clinical dosing group received doses individualized to
      clinical response by the medical team (blinded to Train-of-Four). Differences
      between groups were evaluated by Wilcoxon matched-pairs signed rank test.
      MEASUREMENTS AND MAIN RESULTS: A total of 77 patients (35 standard clinical
      patients vs. 42 peripheral nerve stimulation patients) were enrolled in the
      study. Despite no difference in initial doses and time to reach 90% blockade or
      clinical response between groups, the peripheral nerve stimulation group used
      less drug than the standard clinical group (0.040 +/- 0.028 vs. 0.070 +/- 0.030
      mg/kg/hr, respectively, p = .001). The total cumulative amount of vecuronium for
      the episode of paralysis was greater in the control group (285.8 +/- 246.6 vs.
      137.1 +/- 106.4 mg, p = .001). The peripheral nerve stimulation group recovered
      neuromuscular function (relative risk of 1.85, with 95% confidence interval [CI]
      of 1.02-3.35, p = .039) and spontaneous ventilation (relative risk of 1.86, 95%
      CI 1.00-3.45, p = .047) faster than the control group. In patients, adjusting for
      renal dysfunction, the likelihood of a faster recovery in the peripheral nerve
      stimulation group increased for neuromuscular function (relative risk of 1.89,
      95% CI of 1.07-3.32, p = .018) and spontaneous ventilation (relative risk of
      2.27, 95% CI of 1.23-4.21, p = .019). Patients with combined renal and liver
      failure similarly demonstrated a faster recovery in the peripheral nerve
      stimulation group. The recovery was affected to a lesser extent by adjusting for
      concurrent aminoglycoside and corticosteroid administration. CONCLUSIONS: Use of
      peripheral nerve stimulation for monitoring the degree of blockade and adjusting
      drug doses in continuously paralyzed critically ill medical patients results in
      lower doses of vecuronium to maintain a desired depth of paralysis, and allows a
      faster recovery of neuromuscular function and spontaneous ventilation.

PMID- 9142021
TI  - Pretreatment with inhaled nitric oxide inhibits neutrophil migration and
      oxidative activity resulting in attenuated sepsis-induced acute lung injury.
AB  - OBJECTIVE: To determine if, and by what mechanisms, inhaled nitric oxide
      attenuates acute lung injury in a porcine model of adult respiratory distress
      syndrome induced by Gram-negative sepsis. DESIGN: Nonrandomized, controlled
      study. SETTING: Laboratory at a university medical center. SUBJECTS: Thirty
      pathogen-free Yorkshire swine (15 to 20 kg). INTERVENTIONS: Four groups of swine
      were anesthetized, mechanically ventilated, and studied for 5 hrs. Both control
      nitric oxide and septic-nitric oxide animals received inhaled nitric oxide at 20
      parts per million throughout the study. Control (n = 10) and control-nitric oxide
      (n = 5) animals received a 1-hr infusion of sterile saline. Sepsis was induced in
      septic (n = 10) and septic-nitric oxide (n = 5) animals with a 1-hr intravenous
      infusion of live Pseudomonas aeruginosa. MEASUREMENTS AND MAIN RESULTS: Untreated
      septic animals developed a progressive decrease in Pao2 that was prevented in
      septic-nitric oxide animals (73 +/- 4 vs. 214 +/- 23 torr [9.7 +/- 0.5 vs. 28.5
      +/- 3.1 kPa], respectively, at 5 hrs, p < .05). Untreated septic animals showed a
      significant increase in bronchoalveolar lavage protein and neutrophil count at 5
      hrs, compared with the baseline value, indicating acute lung injury. Septic
      nitric oxide animals showed no significant increase in these parameters.
      Peripheral blood neutrophils from untreated septic animals and septic-nitric
      oxide animals exhibited significant (p < .05) up-regulation of CD18 receptor
      expression and oxidant activity (10.5 +/- 0.9 and 5.0 +/- 0.9 nmol of superoxide
      anion/10(6) neutrophils/10 mins, respectively) compared with both control and
      control-nitric oxide animals (3.0 +/- 0.6 and 2.6 +/- 0.2 nmol of superoxide
      anion/10(6) neutrophils/10 mins, respectively). Also, priming for the oxidant
      burst at 5 hrs was decreased by 50% in septic-nitric oxide animals compared with
      untreated septic animals. Both untreated septic and septic-nitric oxide animals
      showed a significant increase in pulmonary arterial pressure at 30 mins (47.5 +/-
      2.4 and 51.0 +/- 3.0 mm Hg, respectively), followed by a progressive decrease
      (32.8 +/- 2.6 and 31.3 +/- 5.4 mm Hg, respectively, at 5 hrs). Both of these
      changes were significant (p < .05) compared with baseline values and compared
      with the control groups. There was no significant difference in pulmonary
      arterial pressure or systemic arterial pressure at any time between untreated
      septic and septic-nitric oxide animals. CONCLUSIONS: These results demonstrate
      that inhaled nitric oxide attenuates alveolar-capillary membrane injury in this
      porcine model of Gram-negative sepsis but does not adversely affect systemic
      hemodynamics. The data suggest that inhaled nitric oxide preserves alveolar
      capillary membrane integrity by the following means: a) inhibiting
      transendothelial migration of activated, tightly adherent neutrophils; and b)
      possibly by attenuating the neutrophil oxidant burst.

PMID- 9142022
TI  - Decreased plasma gelsolin concentrations in acute liver failure, myocardial
      infarction, septic shock, and myonecrosis.
AB  - OBJECTIVE: To quantitate gelsolin concentrations in serum of patients with a
      variety of conditions involving actin release into the circulation. DESIGN:
      Prospective evaluation of sera on consecutive patients. SETTING: Metropolitan
      county hospital. PATIENTS: Ninety hospital patients with a variety of well
      characterized diseases. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sera
      were studied from patients with acute liver failure (n = 18), chronic hepatitis
      (n = 17), cirrhosis of varying etiology (n = 17), pancreatitis (n = 10), acute
      myocardial infarction (n = 10), myonecrosis due either to polymyositis or crush
      injuries (n = 12), and septic shock (n = 6); results were compared with sera from
      healthy individuals (n = 25). Gelsolin was quantified by Western blotting with
      monoclonal anti-gelsolin and laser densitometry. Significant reductions in mean
      gelsolin concentrations compared with healthy controls were observed in patients
      with acute liver failure (47%), myocardial infarction (69%), sepsis (51%), and
      myonecrosis (66%). An inverse correlation was observed between gelsolin
      concentration and severity of illness, as indicated by the magnitude of serum
      enzyme concentrations. CONCLUSIONS: Gelsolin depletion occurs in a variety of
      tissue injury syndromes. Depletion of actin-scavenger capacity in the presence of
      continued actin release may affect outcome in situations of severe organ damage.

PMID- 9142023
TI  - Blood volume determination using hydroxyethyl starch: a rapid and simple
      intravenous injection method.
AB  - OBJECTIVE: To develop and evaluate a new method for blood volume measurements
      using hydroxyethyl starch as a dilution marker. DESIGN: Laboratory and clinical
      investigation. SETTING: Neurosurgical operating rooms and anesthesiological
      laboratories of a university hospital. PATIENTS: Twelve patients who underwent a
      neurosurgical operation. INTERVENTIONS: Anesthesia and operations were carried
      out by physicians who were not involved in the study. In addition, blood samples
      were drawn from 50 volunteers. MEASUREMENTS AND MAIN RESULTS: Blood volume
      measurements by the hydroxyethyl starch method were validated in vivo by
      comparison with a conventional carbon monoxide technique. Patients were
      intravenously injected with hydroxyethyl starch (100 mL) and received
      simultaneously an injection of carbon monoxide (50 mL) into a closed-circuit
      ventilation system. Blood samples obtained before and 5 mins after injection were
      analyzed for carboxyhemoglobin and glucose plasma concentrations after acidic
      hydrolysis of hydroxyethyl starch. Blood volume was calculated from the
      difference between glucose concentrations measured after hydrolysis in the
      plasma, before and after the addition of hydroxyethyl starch. In vitro, the
      hydroxyethyl starch method had an error and a precision of approximately 2%. In
      vivo, simultaneous measurements of blood volume using hydroxyethyl starch and
      carbon monoxide demonstrated a high correlation (r2 = .96, p < .001) between
      these methods. The mean difference between the two methods relative to their
      average value was 1.0 +/- 3.5%; the bias was 52.3 mL, and the 95% confidence
      interval was -64.0 to +168.7 mL. CONCLUSIONS: Blood volume determination by the
      hydroxyethyl starch method is accurate and rapid and may enhance perioperative
      monitoring of fluid and blood therapy.

PMID- 9142025
TI  - Poor prognosis for existing monitors in the intensive care unit.
AB  - OBJECTIVE: To identify areas requiring the most urgent improvement in the
      intensive care unit (ICU); and to accurately determine the positive predictive
      value of routine critical care patient monitoring alarms, as well as the common
      causes for false-positive alarms. DESIGN: Prospective, observational study.
      SETTING: A multidisciplinary ICU in a university-affiliated children's hospital
      (excluding children with primary heart disease). INTERVENTIONS: The occurrence
      rate, cause, and appropriateness of all alarms from tracked monitors were
      recorded by a trained observer and validated by the bedside nurse over a 10-wk
      period for a single bedspace at a time. MEASUREMENTS AND MAIN RESULTS: After 298
      monitored hrs, 86% of a total 2,942 alarms were found to be false-positive
      alarms, while an additional 6% were classified as clinically irrelevant true
      alarms. Only 8% of all alarms tracked during the study period were determined to
      be true alarms with clinical significance. Alarms were also classified according
      to whether they were clearly associated with a "patient intervention" (18%), were
      clearly not associated with a patient intervention (74%), or had unclear
      association to interventions (8%). While 11% of "nonpatient intervention" alarms
      were clinically significant true alarms, only 2% of "patient intervention" alarms
      were so. Positive predictive values for the various devices ranged from < 1% for
      the pulse oximeter's heart rate signal to 74% for the arterial catheter's mean
      systemic blood pressure signal during periods free from patient interventions.
      The pulse oximeter caused false-positive alarms most frequently, with common
      reasons being bad data format/bad connection and poor contact. CONCLUSION:
      Efforts to develop intelligent monitoring systems have more potential to deliver
      significantly improved patient care by initially targeting especially weak areas
      in ICU monitoring, such as pulse oximetry reliability.

PMID- 9142024
TI  - Cytokines, nitrite/nitrate, soluble tumor necrosis factor receptors, and
      procalcitonin concentrations: comparisons in patients with septic shock,
      cardiogenic shock, and bacterial pneumonia.
AB  - OBJECTIVES: To determine and compare the respective concentrations of tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-6, soluble TNF receptors,
      nitrite/nitrate (NO2-/NO3-), and procalcitonin in the plasma of patients with
      septic shock, cardiogenic shock, and bacterial pneumonia without shock; and to
      assess the predictive value of these mediators in defining patients with septic
      shock. DESIGN: Cohort study, comparing normal volunteers (controls) and patients
      with septic shock, cardiogenic shock, and bacterial pneumonia. SETTING: A
      collaborative study among an intensive care unit, an emergency room, and three
      research laboratories. PATIENTS: Mediators were measured at various times in 15
      patients with septic shock (during the shock phase and during the recovery
      phase), in seven patients with cardiogenic shock during the shock phase, and in
      seven patients with severe bacterial pneumonia on day 1 of admission.
      INTERVENTIONS: Blood samples were collected at various times during the course of
      the disease. MEASUREMENTS AND MAIN RESULTS: TNF-alpha values were highest in the
      acute phase of septic shock (53 to 131 pg/mL during septic shock), while patients
      with bacterial pneumonia had intermediate concentrations (32 pg/mL). TNF-alpha
      concentrations were normal in patients with cardiogenic shock. IL-6
      concentrations were highest in patients with acute septic shock (85 to 385
      pg/mL). However, in contrast to TNF-alpha concentrations, IL-6 concentrations
      were normal in patients with bacterial pneumonia and increased in patients with
      cardiogenic shock (78 pg/mL). Soluble TNF receptors were increased in all three
      groups vs. controls, with the highest increase in patients with septic shock. NO2
      /NO3- concentrations were highest (72 to 140 mM) in patients with septic shock,
      and were < 40 mM in the other groups of patients. Procalcitonin concentrations
      were only markedly increased in patients with septic shock (72 to 135 ng/mL,
      compared with approximately 1 ng/mL in the three other groups). The best
      predictive value for septic shock was found to be the measurements of NO2-/NO3-
      and procalcitonin concentrations. CONCLUSIONS: These observations showed that
      increase of proinflammatory cytokines was a consequence of inflammation, not of
      shock. In this study comparing various shock and infectious states, measurements
      of NO2-/NO3- concentration and procalcitonin concentration represented the most
      suitable tests for defining patients with septic shock.

PMID- 9142027
TI  - Bedside videoscopic placement of feeding tubes: development of fiberoptics
      through the tube.
AB  - OBJECTIVE: Transpyloric small intestine feeding tube placement can be difficult
      and tedious. Currently accepted techniques are associated with disadvantages and
      risk. The purpose of this study is to describe the development of a new
      technique: bedside videoscopic placement using fiberoptics through the tube.
      DESIGN: Prospective, descriptive case study. SETTING: Intensive care unit in a
      teaching hospital. PATIENTS: Subjects were divided into two groups: a) group 1:
      eight healthy volunteers (seven male, one female); b) group 2: nine critically
      ill patients (six male, three female; eight of these patients were intubated).
      INTERVENTIONS: Standard 12-Fr (4.0-mm) feeding tubes (n = 19) were placed. Two
      patients from group 2 had feeding tubes placed on two separate occasions. The
      feeding tubes were inserted by the oral (n = 8) or nasal (n = 11) route under
      direct vision, using a 6.7-Fr (2.2-mm) fiberoptic scope through the feeding tube.
      MEASUREMENTS AND MAIN RESULTS: We visualized enteric structures clearly through
      the feeding tube in all subjects and patients. Based on visual landmarks, we
      advanced the feeding tube through the pylorus and into the duodenum in all
      individuals. Transpyloric tube placement was confirmed videoscopically (n = 19)
      and radiographically (n = 18). In three subjects from group 1, the feeding tube
      entered the first part of the duodenum, while, in the remainder of the subjects,
      the tube passed into or beyond the second portion of the duodenum. In eight (73%)
      of 11 attempts on the nine critically ill patients from group 2, the feeding
      tubes were advanced to the distal duodenum or jejunum. The time required for
      placement in group 2 ranged from 2 to 43 mins (mean 18 +/- 12 [SD]). The feeding
      tubes remained in place 10 +/- 4 days and patients met their estimated caloric
      needs within 24 hrs. Residual volumes of nutrition in the small bowel were < 5
      mL. There were no documented episodes of aspiration. CONCLUSION: This new
      technique has the potential for rapid, accurate, and safe feeding tube placement
      in patients requiring nutritional support.

PMID- 9142026
TI  - Randomized, prospective trial of bilevel versus continuous positive airway
      pressure in acute pulmonary edema.
AB  - OBJECTIVE: To evaluate whether bilevel positive airway pressure, by actively
      assisting inhalation, more rapidly improves ventilation, acidemia, and dyspnea
      than continuous positive airway pressure (CPAP) in patients with acute pulmonary
      edema. DESIGN: Randomized, controlled, double-blind trial. SETTING: Emergency
      department in a university hospital. PATIENTS: Twenty-seven patients, presenting
      with acute pulmonary edema, characterized by dyspnea, tachypnea, tachycardia,
      accessory muscle use, bilateral rales, and typical findings of congestion on a
      chest radiograph. INTERVENTIONS: In addition to standard therapy, 13 patients
      were randomized to receive nasal CPAP (10 cm H2O), and 14 patients were
      randomized to receive nasal bilevel positive airway pressure (inspiratory and
      expiratory positive airway pressures of 15 and 5 cm H2O, respectively) in the
      spontaneous/timed mode that combines patient flow-triggering and backup time
      triggering. MEASUREMENTS AND MAIN RESULTS: After 30 mins, significant reductions
      in breathing frequency (32 +/- 4 to 26 +/- 5 breaths/min), heart rate (110 +/- 21
      to 97 +/- 20 beats/min), blood pressure (mean 117 +/- 28 to 92 +/- 18 mm Hg), and
      Paco2 (56 +/- 15 to 43 +/- 9 torr [7.5 +/- 2 to 5.7 +/- 1.2 kPa]) were observed
      in the bilevel positive airway pressure group, as were significant improvements
      in arterial pH and dyspnea scores (p < .05 for all of these parameters). Only
      breathing frequency improved significantly in the CPAP group (32 +/- 4 to 28 +/-
      5 breaths/min, p < .05). At 30 mins; the bilevel positive airway pressure group
      had greater reductions in Paco2 (p = .057), systolic blood pressure (p = .005),
      and mean arterial pressure (p = .03) than the CPAP group. The myocardial
      infarction rate was higher in the bilevel positive airway pressure group (71%)
      compared with both the CPAP group (31%) and historically matched controls (38%)
      (p = .05). Duration of ventilator use, intensive care unit and hospital stays,
      and intubation and mortality rates were similar between the two groups.
      CONCLUSIONS: Bilevel positive airway pressure improves ventilation and vital
      signs more rapidly than CPAP in patients with acute pulmonary edema. The higher
      rate of myocardial infarctions associated with the use of bilevel positive airway
      pressure highlights the need for further studies to clarify its effects on
      hemodynamics and infarction rates, and to determine optimal pressure settings.

PMID- 9142028
TI  - Central and regional hemodynamics during acute hypovolemia and volume
      substitution in volunteers.
AB  - OBJECTIVES: To study the central and regional hemodynamics and oxygen consumption
      during acute hypovolemia and volume replacement with crystalloid and colloid
      solutions. DESIGN: Prospective, randomized, laboratory investigation. SETTING:
      Clinical physiology department at a university hospital. SUBJECTS: Eighteen
      healthy male volunteers, between 21 and 35 yrs of age (mean 26). INTERVENTIONS:
      Catheters were inserted in the cubital vein, brachial artery, pulmonary artery,
      thoracic aorta, right hepatic vein, and left renal vein for measurements of
      systemic arterial and pulmonary arterial pressures, total and central blood
      volumes, extravascular lung water, and the splanchnic (liver) and renal blood
      flow rates. The exchange of respiratory gases was measured, using the Douglas bag
      technique. Measurements were made before and after a venesection of 900 mL and
      again after the subjects had been randomized and received volume replacement with
      either 900 mL of Ringer's acetate solution 900 mL of albumin 5%, or 900 plus 900
      mL of Ringer's solution. MEASUREMENTS AND MAIN RESULTS: Withdrawal of 900 mL of
      blood decreased cardiac output and the splanchnic and renal blood flow rates by
      between -16% and -20%. The oxygen uptake decreased by 13% in the whole body,
      while it remained unchanged in the liver and kidney. The systemic and pulmonary
      vascular resistances increased, while the extravascular lung water decreased.
      Autotransfusion of fluid from tissue to blood was indicated by hemodilution,
      which was most apparent in subjects showing only a minor change in peripheral
      resistance. Cardiac output, blood volume, and systemic vascular resistance were
      significantly more increased by infusion of 900 mL of albumin 5% than by 900 mL
      of Ringer's solution. However, infusion of 1800 mL of Ringer's solution increased
      the extravascular lung water and the pulmonary arterial pressures to
      significantly above baseline, while no significant difference from baseline was
      found after 900 mL of Ringer's acetate solution. CONCLUSIONS: Withdrawal of 900
      mL of blood induces similar reductions in cardiac output as in the splanchnic and
      renal blood flow rates. A fluid shift from the extravascular to the intravascular
      fluid compartment might restore up to 50% of the blood loss. Optimal volume
      substitution with Ringer's solution can be effectuated by infusing between 100%
      and 200% of the amount of blood lost.

PMID- 9142029
TI  - A new technique for placement of nasoenteral feeding tubes using external
      magnetic guidance.
AB  - OBJECTIVE: To evaluate a new technique in which a hand-held external magnet is
      used to maneuver nasoenteral feeding tubes through the pylorus and into the
      duodenum. DESIGN: Prospective case series. SETTING: Critical care units and
      medical and surgical wards of a university-affiliated community hospital.
      PATIENTS: Thirty-five patients were entered into the study after the attending
      physician requested assistance in tube placement. INTERVENTIONS: A standard 12
      Fr, 114-cm flexible nasoenteral feeding tube was modified by inserting a small
      magnet into the distal tip. The tube was inserted per nares into the stomach,
      using traditional technique. Next, an external magnet was placed over the right
      upper abdominal quadrant, at the midclavicular line to attract the tube tip along
      the lesser curvature of the stomach, through the pyloric sphincter, and into the
      duodenum. Portable abdominal radiography performed immediately after the
      procedure confirmed the anatomic location of the tube tip. MEASUREMENTS AND MAIN
      RESULTS: Forty-two intubations were performed in 35 patients (in seven patients,
      the tube had to be reinserted due to inadvertent removal or surgery). In 37 (88%)
      of 42 intubations, the tube was passed through the pyloric sphincter and into the
      duodenum on the first attempt. The mean procedure time was 15 +/- 9 mins (range
      10 to 45). There were no complications related to the procedure during the study
      period. CONCLUSIONS: This report describes a novel technique of enteral feeding
      tube placement, using external magnetic guidance. Transpyloric placement was
      achieved in 88% of cases. This reliable and convenient bedside method for rapid
      placement of the tube into the duodenum allows prompt and safe initiation of
      enteral nutrition.

PMID- 9142030
TI  - Regulation of beta 2-adrenergic receptors on mononuclear leukocytes in patients
      with acute ischemic heart disease.
AB  - OBJECTIVE: To investigate relationships between acute adrenergic stress, plasma
      catecholamine concentrations, and beta 2-adrenergic receptors. DESIGN:
      Prospective, descriptive study. SETTING: Emergency medical service at a
      university hospital. PATIENTS: Twenty-seven patients with out-of-hospital cardiac
      arrest (n = 11), myocardial infarction (n = 6), and angina pectoris (n = 10), and
      12 control subjects. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Mononuclear leukocyte beta 2-adrenergic receptor density and affinity were
      measured in patients 15 mins after successful cardiopulmonary resuscitation and
      after the diagnosis of myocardial infarction or angina pectoris, respectively,
      and were measured as well in control subjects. Plasma concentrations of
      catecholamines, glucose, and lactate were simultaneously measured with heart rate
      and blood pressure. After cardiac arrest, the density of beta 2-adrenergic
      receptors (1858 +/- 188 sites/cell [p < .01]), plasma epinephrine concentration
      (31,990 +/- 14,526 pg/mL [174.6 +/- 79.3 nmol/L] [p < .01]), heart rate (100 +/-
      6 beats/min [p < .01]), glucose concentration (14.9 +/- 0.8 mmol/L [p < .01]),
      and lactate concentration (10.9 +/- 0.6 mmol/L [p < .01]) were increased in
      patients compared with those values in healthy controls. CONCLUSION: Acute
      maximal stress, such as after cardiac arrest, is associated with an increase in
      the density of beta 2-adrenergic receptors on mononuclear leukocytes derived from
      patients after successful cardiopulmonary resuscitation.

PMID- 9142031
TI  - Reduction of bleomycin-induced acute DNA injury in the rat lung by the 21
      aminosteroid, U-74389G.
AB  - OBJECTIVE: To determine whether pretreatment with a 21-aminosteroid, U-74389G,
      can prevent subsequent DNA injury in bleomycin-exposed lungs. SUBJECTS: Thirty
      six adult male Sprague-Dawley rats. DESIGN: Controlled animal laboratory
      investigation of DNA injury in vivo. INTERVENTIONS: Animals were treated with 21
      aminosteroid (10 mg/kg) or vehicle and subsequently received intratracheal
      instillation of bleomycin (1.75 U) or normal saline. MEASUREMENTS AND MAIN
      RESULTS: Twenty-four hours after bleomycin exposure, the 21-aminosteroid-treated
      animals had decreased evidence of DNA injury, expressed as percentage of DNA
      fragmentation normalized to the control group (113.5 +/- 6 [SEM] vs. 132 +/-
      3.9%, p < or = .05), and activity of the DNA repair enzyme poly ADP-ribose
      synthetase (3.4 +/- 0.2 vs. 5.6 +/- 0.9 pmol nicotinamide adenine
      dinucleotide/min/mg protein, p < or = .05). Only bleomycin-exposed (+ vehicle)
      animals demonstrated significant evidence of increased DNA injury vs. the
      intratracheal saline-exposed control groups. CONCLUSIONS: The 21-aminosteroid
      pretreatment decreases subsequent pulmonary DNA injury induced by bleomycin
      exposure. This finding is likely due to the 21-aminosteroid's iron-chelating and
      cell-permeating abilities, and suggests that these agents may be effective in
      other diseases where iron-dependent free radical reactions occur.

PMID- 9142032
TI  - Myocardial collagen changes and edema in rats with hyperdynamic sepsis.
AB  - OBJECTIVE: To determine if sepsis, which is accompanied by both systolic and
      diastolic myocardial dysfunction, involves changes in myocardial collagen, as
      myocardial collagen changes can affect both myocardial compliance and
      contractility. DESIGN: Prospective, randomized, controlled study. SETTING: Animal
      laboratory at a university-affiliated hospital. SUBJECTS: Male Sprague-Dawley
      rats, weighing 310 to 396 g. INTERVENTIONS: Cecal ligation and perforation (to
      induce sepsis) for 24 (n = 9) or 48 hrs (n = 9); sham laparotomy for 24 (n = 10)
      or 48 hrs (n = 9) with saline fluid resuscitation or normal control (n = 5)
      groups. MEASUREMENTS AND MAIN RESULTS: Collagen content and interstitial space
      were determined, using polarized light microscopy and a computer video
      densitometry system. At 24 and 48 hrs post surgery, heart rate and cardiac index
      were increased, and systemic vascular resistance index was decreased
      significantly in the sepsis vs. the sham rats. Collagen content was decreased
      significantly in the sepsis vs. the sham groups both at 24 and 48 hrs following
      surgery (1.83 +/- 0.79 [SD] % [24 hrs], 1.76 +/- 0.31% [48 hrs] vs. 2.83 +/-
      0.73% [24 hrs], 2.25 +/- 0.72% [48 hrs]; p < .01). Interstitial space was
      increased significantly in the sepsis vs. the sham groups (13.9 +/- 3.5% [24
      hrs], 15.6 +/- 5.2% [48 hrs] vs. 8.6 +/- 4.2% [24 hrs], 9.9 +/- 4.8% [48 hrs]; p
      < .01). CONCLUSIONS: Sepsis is accompanied by changes in myocardial collagen
      content and myocardial edema. These changes may contribute to the systolic and
      diastolic myocardial dysfunction, and particularly to the ventricular dilation,
      observed in sepsis.

PMID- 9142033
TI  - Dopexamine improves liver oxygenation during crystalloid resuscitation from
      experimental hemorrhagic shock.
AB  - OBJECTIVE: To evaluate the effects of dopexamine administration on hemodynamic
      variables and tissue oxygen tensions during crystalloid resuscitation from
      hemorrhagic shock. DESIGN: Randomized, control trial. SETTING: An animal
      laboratory at a university center. SUBJECTS: Twelve piglets, mean weight 22 kg.
      INTERVENTIONS: The animals were anesthetized and bled to a state of hemorrhagic
      shock and resuscitated, using a crystalloid solution infused at a rate of
      approximately 2.6 mL/min/kg (total amount 208 mL/kg). Cardiac output and mean
      arterial pressure (MAP were measured as indicators of volume filling during the
      20- to 30-min resuscitation period and during the follow-up period until 80 mins
      from the start of resuscitation. Dopexamine was administered by infusion at 6
      micrograms/kg-min from the start of volume replacement (dopexamine group, n = 6).
      The rest of the animals (control group, n = 6) were given volume replacement
      only. MEASUREMENTS AND MAIN RESULTS: Systemic oxygen transport variables were
      calculated. Tissue oxygen tensions were continuously recorded from the liver,
      conjunctival layer, and via subcutaneous and transcutaneous electrodes in the
      abdominal region. MAP decreased from 119 +/- 2 (SEM) to 44 +/- 2 mm Hg and
      cardiac output decreased by 77% during the shock period. During resuscitation,
      cardiac output was restored in both groups. MAP increased close to the baseline
      during the early resuscitation period and decreased slowly during follow-up.
      Oxygen delivery remained at 46% of baseline, whereas systemic oxygen consumption
      was restored during resuscitation in both groups. Liver tissue oxygen tension
      increased well above baseline during resuscitation in the dopexamine group, and
      liver tissue oxygen tension was significantly higher than in the control group.
      After 60 mins of resuscitation, the liver oxygen tension decreased to control
      group values. None of the other tissue oxygen tensions showed any differences
      between groups. CONCLUSIONS: Dopexamine administration during crystalloid
      resuscitation from hemorrhagic shock was well tolerated and resulted in
      significant and specific, although transient, improvement in liver oxygenation.

PMID- 9142035
TI  - Partial carbon dioxide rebreathing: a reliable technique for noninvasive
      measurement of nonshunted pulmonary capillary blood flow.
AB  - OBJECTIVE: To determine the validity and clinical utility of the partial CO2
      rebreathing technique for measurement of nonshunted pulmonary capillary blood
      flow and cardiac output. DESIGN: Prospective, controlled animal laboratory
      investigation and clinical trial. SETTINGS: Animal research facility and
      intensive care unit of a university hospital. SUBJECTS: Fifteen adult sheep,
      weighting 58 to 78 kg. PATIENTS: Mechanically ventilated patients with different
      underlying diseases (n = 12) and with adult respiratory distress syndrome (ARDS)
      (n = 8). INTERVENTIONS: CO2 elimination rate (VCO2) was measured breath-by-breath
      with a system developed for the study and also by gas collection (validation
      procedure in patients with different underlying diseases). Partial CO2
      rebreathing maneuvers, cardiac output by thermodilution, and blood gas analysis
      were performed in sheep with lung atelectasis and in patients with ARDS.
      MEASUREMENTS AND MAIN RESULTS: The degree of correlation between VCO2 measured
      with the system developed and gas collection was very good (r2 = .95, p < .0001),
      and bias and precision calculations (1 +/- 9 mL/min) showed close agreement
      between methods. The overall degree of correlation between partial CO2
      rebreathing measurements and cardiac output was moderate (r2 = .54, p < .0001),
      the noninvasive method tending to underestimate cardiac output, as shown by bias
      and precision calculations (-1.69 +/- 1.90 L/min). In contrast, the overall
      degree of correlation between partial CO2 rebreathing measurements and nonshunted
      pulmonary capillary blood flow was good (r2 = .73, p < .0001). Bias and precision
      calculations (0.25 +/- 0.83 L/min) showed a tendency for the partial CO2
      rebreathing technique to slightly overestimate pulmonary capillary blood flow.
      Variance differences between partial CO2 rebreathing measurements and cardiac
      output could be mostly explained by intrapulmonary right-to-left shunt fraction
      (r2 = .51, p < .0001). CONCLUSIONS: Our results support the use of the system
      developed for breath-by-breath VCO2 measurements. The lack of agreement between
      partial CO2 rebreathing measurements and cardiac output was mostly explained by
      intrapulmonary right-to-left shunt, suggesting that this technique may not be
      appropriate for monitoring cardiac output in patients with increased venous
      admixture. In contrast, our results demonstrate that the partial CO2 rebreathing
      technique is reliable for measurement of the effective nonshunted pulmonary
      capillary blood flow. This technique may prove useful to guide ventilatory
      therapy adjustments in an attempt to optimize nonshunted pulmonary capillary
      blood flow.

PMID- 9142034
TI  - Epinephrine and sodium bicarbonate independently and additively increase survival
      in experimental amitriptyline poisoning.
AB  - OBJECTIVES: Cardiac depression is the main adverse effect of severe tricyclic
      antidepressant poisoning. The aim of this study was to investigate whether
      treatment with epinephrine or norepinephrine increases survival as compared with
      standard treatment with sodium bicarbonate in experimental amitriptyline
      poisoning. DESIGN: Nonrandomized, controlled intervention trial. SETTING:
      University laboratory. SUBJECTS: Male, anesthetized, paralyzed, and mechanically
      ventilated Sprague-Dawley rats (n = 91). INTERVENTIONS: Rats subjected to a 60
      min infusion of amitriptyline (2 mg/kg/min) were treated with a continuous
      infusion of either epinephrine, norepinephrine, sodium bicarbonate, epinephrine
      plus sodium bicarbonate, norepinephrine plus sodium bicarbonate, or placebo.
      MEASUREMENTS AND MAIN RESULTS: Inotropic drug treatment was associated with an
      increased survival rate as compared with treatment with sodium bicarbonate and
      treatment with placebo. Epinephrine treatment was superior to norepinephrine.
      Additional treatment with sodium bicarbonate increased survival rate for each
      inotropic drug. Sodium bicarbonate and inotropic drug treatment independently
      increased the survival rate (p < .001 for both effects). No interaction between
      these two treatment effects was observed. CONCLUSIONS: Both epinephrine and
      norepinephrine increased the survival rate in tricyclic antidepressant poisoning
      in rats. Sodium bicarbonate increased the survival rate independent of inotropic
      drug treatment. Furthermore, epinephrine was superior to norepinephrine when used
      both with and without sodium bicarbonate, and the most effective treatment was
      epinephrine plus sodium bicarbonate.

PMID- 9142036
TI  - Nitric oxide does not mediate lipopolysaccharide-induced myocardial depression in
      guinea pigs.
AB  - OBJECTIVE: To determine the role of nitric oxide as a mediator of
      lipopolysaccharide-induced myocardial depression. DESIGN: Prospective, controlled
      study. SETTING: University research laboratory. SUBJECTS: Male and female Hartley
      guinea pigs. INTERVENTIONS: Animals (n = 97) received intraperitoneal injections
      of either saline or Escherichia coli lipopolysaccharide (2 mg/kg). Some (n = 5)
      animals received two injections of dexamethasone before lipopolysaccharide. Left
      atria were harvested 6 hrs (n = 20) or 16 hrs (n = 77) later and placed in a
      tissue bath with Krebs-Henseleit buffer. Contractile tension was measured in the
      presence or absence of two inhibitors of nitric oxide synthase (NG-nitroarginine
      [NNA] or aminoguanidine). Atrial and serum nitrite/ nitrate and atrial cyclic
      guanosine monophosphate (cGMP) concentrations were assayed. MEASUREMENTS AND MAIN
      RESULTS: Lipopolysaccharide caused significant atrial contractile depression at
      16 hrs but not 6 hrs compared with control animals. Neither NNA nor
      aminoguanidine reversed the depression in atrial function. In contrast, exposure
      of control atria to NNA worsened contractile function. There were no significant
      differences between control and lipopolysaccharide-treated animals in atrial and
      serum nitrite/nitrate and atrial cGMP concentrations. CONCLUSIONS: Nitric oxide
      does not mediate lipopolysaccharide-induced myocardial depression in this animal
      model. Basal concentrations of nitric oxide may be important since NNA worsened
      contractile function in control atria.

PMID- 9142037
TI  - Significant reduction in minute ventilation and peak inspiratory pressures with
      arteriovenous CO2 removal during severe respiratory failure.
AB  - OBJECTIVES: To quantify CO2 removal using an extracorporeal low-resistance
      membrane gas exchanger placed in an arteriovenous shunt and evaluate its effects
      on the reduction of ventilatory volumes and airway pressures during severe
      respiratory failure induced by smoke inhalation injury. DESIGN: Prospective
      study. SETTING: Research laboratory. SUBJECTS: Adult female sheep (n = 5).
      INTERVENTIONS: Animals were instrumented with femoral and pulmonary arterial
      catheters and underwent an LD50 cotton smoke inhalation injury via a tracheostomy
      under halothane anesthesia. Twenty-four hours after smoke inhalation injury, the
      animals were reanesthetized and systemically heparinized for cannulation of the
      left carotid and common jugular vein to construct a simple arteriovenous shunt. A
      membrane gas exchanger was interposed within the arteriovenous shunt, and blood
      flow produced by the arteriovenous pressure gradient was unrestricted at the time
      of complete recovery from anesthesia. CO2 removal by the gas exchanger was
      measured as the product of the sweep gas flow (FIO2 of 1.0 at 2.5 to 3.0 L/min)
      and the exhaust CO2 content measured with an inline capnometer. CO2 removed by
      the animal's lungs was determined by the expired gas CO2 content in a Douglas
      bag. We made stepwise, 20% reductions in ventilator support hourly. We first
      reduced the tidal volume to achieve a peak inspiratory pressure of < 30 cm H2O,
      and then we reduced the respiratory rate while maintaining normocapnia. PaO2 was
      maintained by adjusting the FIO2 and the level of positive end-expiratory
      pressure. MEASUREMENTS AND MAIN RESULTS: Mean blood flow through the
      arteriovenous shunt ranged from 1154 +/- 82 mL/min (25% cardiac output) to 1277
      +/- 38 mL/min (29% cardiac output) over the 6-hr study period. The pressure
      gradient across the gas exchanger was always < 10 mm Hg. Maximum arteriovenous
      CO2 removal was 102.0 +/- 9.5 mL/min (96% of total CO2 production), allowing
      minute ventilation to be reduced from 10.3 +/- 1.4 L/min (baseline) to 0.5 +/-
      0.0 L/min at 6 hrs of arteriovenous CO2 removal while maintaining normocapnia.
      Similarly, peak inspiratory pressure decreased from 40.8 +/- 2.1 to 19.7 +/- 7.5
      cm H2O. PaO2 was maintained at > 100 torr (> 13.3 kPa) at maximally reduced
      ventilator support. Mean arterial pressure and cardiac output did not change
      significantly as a result of arteriovenous shunting. CONCLUSIONS: Extracorporeal
      CO2 removal using a low-resistance gas exchanger in a simple arteriovenous shunt
      allows significant reduction in minute ventilation and peak inspiratory pressure
      without hypercapnia or the complex circuitry and monitoring required for
      conventional extracorporeal membrane oxygenation. Arteriovenous CO2 removal can
      be applied as an easy and cost-effective treatment to minimize ventilator-induced
      barotrauma and volutrauma during severe respiratory failure.

PMID- 9142038
TI  - Extracorporeal membrane oxygenation exposes infants to the plasticizer, di(2
      ethylhexyl)phthalate.
AB  - OBJECTIVES: To determine the exposure to, and evaluate the potential toxicity
      from, the plasticizer, di(2-ethylhexyl)phthalate (DEHP) during extracorporeal
      membrane oxygenation (ECMO) therapy. DESIGN: Protocol 1 consisted of a
      prospective comparison of three ECMO circuit designs in vitro. Protocol 2
      consisted of a prospective, comparative clinical study evaluating DEHP plasma
      concentrations in ECMO vs. non-ECMO patients with respiratory failure. SETTING:
      Neonatal intensive care unit at The Children's National Medical Center,
      Washington, DC. PATIENTS: In protocol 2, 28 consecutive term infants were
      referred for ECMO therapy. Eighteen infants required ECMO; ten control patients
      received conventional ventilation and improved without ECMO. INTERVENTIONS: In
      protocol 1, three ECMO circuit designs were primed in vitro with normal saline,
      albumin, and human blood, which was maintained at 37 degrees C and recirculated
      at 400 mL/min for 48 hrs. Plasma samples were obtained at time 0, 1 hr, and every
      6 hrs. In protocol 2, ventilatory and cardiovascular management of the patients
      in the study was conducted by the attending physician. Patients were placed on
      ECMO when they met the institutional criteria for ECMO therapy. Daily plasma
      concentrations for DEHP were collected until 3 days after decannulation from
      bypass in the ECMO group. Control patients were sampled daily until extubation.
      Evidence of cardiac, liver, or lung toxicity was evaluated by Chest Radiographic
      Scores, liver function studies, and echocardiograms obtained on day 1, day 3, and
      the day of decannulation in the ECMO group, or at the time of extubation in the
      control group. Sedation, blood product transfusions as indicated, antibiotics,
      and hyperalimentation were administered to all patients. MEASUREMENTS AND MAIN
      RESULTS: All DEHP plasma concentrations were measured by gas chromatography. In
      protocol 1, three circuits were studied: circuit A (small surface area); circuit
      B (larger surface area); and circuit C (surface area of A but with heparin-bonded
      tubing in the circuit). DEHP leached from circuit A at 0.32 +/- 0.12 microgram/
      mL/hr, compared with 0.57 +/- 0.14 microgram/mL/hr from circuit B (p < .05). This
      amount of DEHP extrapolates in the ECMO patient to a potential exposure of 20 to
      70 times that exposure from other medical devices or procedures, such as
      transfusions, dialysis, or short-term cardiopulmonary bypass. Circuit C showed
      almost no leaching from the circuit; DEHP concentrations decreased at a rate of
      0.2 +/- 0.04 microgram/mL/ hr. In protocol 2, DEHP was undetected in the control
      patients. DEHP concentrations in ECMO patients were greater in the early course
      of ECMO. However, most patients cleared this compound from the plasma before
      decannulation. In contrast to the in vitro results in protocol 1, the average
      highest concentration at any time on bypass was 8.3 +/- 5.7 micrograms/mL or 2
      mg/kg. CONCLUSIONS: DEHP leaches from ECMO circuits, with potential exposure
      concentrations related to the surface area of the tubing in the ECMO circuit.
      Heparin bonding of the tubing eliminates this risk. Although significant
      concentrations of DEHP leach from the nonheparin-bonded circuits over time, our
      in vivo studies showed that the DEHP plasma concentrations were less than the
      previously reported values and do not correlate with any observable short-term
      toxicity. This compound may be either efficiently metabolized by the newborn, or
      redistributed into various tissues. Although signs of toxicity were not found in
      this study, long-term complications from chronic exposure to DEHP have not been
      determined.

PMID- 9142039
TI  - Does pediatric housestaff experience influence tests ordered for infants in the
      neonatal intensive care unit?
AB  - OBJECTIVE: To assess the relationship between the experience of pediatric
      housestaff and tests ordered on infants in the neonatal intensive care unit
      (ICU). DESIGN: Prospective, cohort study over one full academic year. SETTING:
      One academic Level III neonatal intensive care nursery. PATIENTS: Data were
      collected prospectively on all 785 infants admitted to the neonatal ICU from July
      1993 to June 1994. These infants were cared for by 14 different categorical
      pediatric housestaff. MEASUREMENTS AND MAIN RESULTS: Our neonatal ICU has either
      a resident or an intern on-call by himself/herself at night, affording us a
      natural setting to compare intern vs. resident test ordering. The outcomes of
      interest were number of arterial blood gases, radiographs, and electrolytes
      ordered per infant by the on-call pediatric houseofficer, as tabulated the
      morning after the call night. Control variables included the severity-of-illness
      of the individual infant (using the Neonatal Therapeutic Intervention Scoring
      System), the workload of the houseofficer (number of patients, number of
      admissions), and supervision (rounding frequency and on-call attending).
      Controlling for the severity-of-illness of the infant, the workload on the call
      night, and supervision with multiple linear regression, we found that interns
      ordered significantly (p = .02) greater numbers of arterial blood gases per
      infant than residents, amounting to some 0.33 blood gases per infant per call
      night (3.22 vs. 2.89 arterial blood gases per infant per night). This increase of
      0.33 blood gases per infant amounts to interns ordering $169 more arterial blood
      gases per call night at our institution. There was no difference between interns
      and residents in ordering radiographs or electrolytes. CONCLUSION: Interns order
      significantly more arterial blood gases per infant than junior and senior
      residents on-call in the neonatal ICU. Additional study is required to see if the
      experience of housestaff is associated with a broader array of neonatal outcomes,
      such as morbidity and mortality.

PMID- 9142040
TI  - Hillary, Bill, and you: volunteerism in the Society of Critical Care Medicine.
      The presidential address from the 26th Educational and Scientific Symposium of
      the Society of Critical Care Medicine.

PMID- 9142041
TI  - Maximizing oxygen delivery in high-risk surgical patients.

PMID- 9142042
TI  - Performance of the Pediatric Risk of Mortality Score.

PMID- 9142043
TI  - The British Society of Gastroenterology diamond jubilee meeting. Brighton, 18-21
      March 1997. Abstracts.

PMID- 9142044
TI  - Mentoring in biomedicine.

PMID- 9142045
TI  - Beta 2 (CD11/CD18) integrins can serve as signaling partners for other leukocyte
      receptors.
AB  - Fig. 1 depicts our current thinking about the ways in which Mo1 and p150,95 form
      cis interactions with other leukocyte receptors. With respect to the associations
      of Mo1 with Fc gamma RIIIB and uPAR, the inhibitory effect of saccharides such as
      NADG suggests a lectin-carbohydrate interaction that may involve the recognition
      of Mo1's beta-glucan site for N-linked carbohydrates4 that are expressed by both
      Fc gamma RIIIB and uPAR. This hypothesis is supported by the results of Stockl et
      al., who showed that the binding of C-terminal-specific mAb VIM12 to Mo1, which
      enhances the phospholipase C-mediated release of Fc gamma RIIIB, was inhibited by
      NADG. However, unlike the sample lectin-carbohydrate interaction that appears to
      govern the association between Mo1 and Fc gamma RIIIB, effective Mo1-dependent
      uPAR signaling also depends on the binding of intact uPA to uPAR (the receptor
      binding ATF of uPA proving insufficient to prime neutrophils for an enhanced
      burst response to FMLP). We speculate that ATF (residues 6-135) binds to uPAR
      while the carboxyl terminal fragment (residues 136-411), which includes a
      glycosylation site at residue 144, binds to the lectinlike site of Mo1, thus
      fostering the linkage between the two receptors. In support of this model is the
      fact that exposure of neutrophils to ATF reduced the degree of molecular
      proximity between Mo1 and uPAR (the latter probably occupied by endogenous intact
      uPA) and increased the molecular association between Mo1 and Fc gamma RIIIB (both
      as detected by quantitative RET). This hypothesis is analogous to the concept
      proposed by Nykjaer et al in which plasminogen activator inhibitor-1 initially
      binds to uPA to form a complex that secondarily binds to the alpha 2
      macroglobulin receptor, leading to internalization of the complex. Whereas the
      contribution of intact uPA to the interaction between Mo1 and uPAR remains
      speculative (based on the indirect data available), no such ambiguity exists for
      the role of the LPS/LBP ligand in regulating the association between Mo1 and
      CD14. In this circumstance, no physical linkage exists between the two receptors
      without the ligand complex. This observation is consistent with the previously
      described affinity of the beta 2 integrins for LPS, leading to the notion that
      the LPS portion of the LPS/LPB complex binds to Mo1, serving to link it with
      LPS/LBP bound to CD14. The observed reversibility of the interactions between the
      integrin glycoproteins and uPAR or CD14 illustrates the fact that these
      associations can be highly dynamic and tied to cellular processes that include
      directed motility (Mo1-uPAR), adherence to substrates (Mo1-CD14), and energy
      metabolism (p150,95-uPAR). We speculate that the GPI-anchored receptor proteins
      serve as rapidly diffusible, expendable "scouts" for the beta 2 integrins, which
      serve to expand their ligand binding repertoire in a cis-acting fashion.

PMID- 9142046
TI  - Prevalence and clinical significance of IgG isotype anti-beta 2-glycoprotein I
      antibodies in antiphospholipid syndrome: a comparative study with anticardiolipin
      antibodies.
AB  - To investigate the prevalence, significance, and specificity of IgG isotype anti
      beta 2-Glycoprotein I antibodies (a-beta 2-GPI) in antiphospholipid syndrome
      (APS), we developed an enzyme-linked immunosorbent assay (ELISA) for the
      detection of IgG-a-beta 2-GPI and tested sera from 61 patients with autoimmune
      disorders (AID), 39 patients with APS and 22 patients with systemic lupus
      erythematosus without APS, 139 patients with various infectious diseases
      (hepatitis C virus infection, human immunodeficiency virus infection, Q fever,
      Mediterranean spotted fever, syphilis) and 97 healthy control subjects. Using
      irradiated plates coated with human beta 2-GPI, we showed that in the sera of
      patients with AID, optical densities from the coated wells were significantly
      higher than those from the noncoated ones (p = 0.0001). In this assay, intra
      assay and inter-assay variation coefficients ranged between 4% and 10%. Clinical
      evaluation showed that IgG-a-beta 2-GPI were found in 23 of 61 patients with AID
      but in only one patient with an infectious disease. The presence of the IgG-a
      beta 2-GPI in association with APS (p = 0.005) was statistically significant with
      high specificity (98%) and positive predictive value (87.5%) but with low
      sensitivity (54%), and was significantly associated with venous thrombosis (p =
      0.0025). In addition, the IgG-a-beta 2-GPI levels were highly correlated with
      those of anticardiolipin antibodies (aCL) (p < 0.001). In contrast to a-beta 2
      GPI, aCL were found with a high prevalence (40%) in patients with infectious
      diseases. Because of their high specificity, anti-beta 2-GPI antibodies appear to
      be useful tools in the evaluation of the risk of APS. However, because of their
      low sensitivity, their detection needs to be associated with that of aCL.

PMID- 9142047
TI  - Platelet activation and platelet-erythrocyte aggregates in patients with sickle
      cell anemia.
AB  - Vascular occlusion and vasculopathy underlie much of the morbidity in patients
      with sickle cell anemia. Platelets may play a role in this vasculopathy. Samples
      from 12 adults patients with sickle cell anemia were examined for evidence of
      platelet activation and formation of platelet-erythrocyte aggregates (PEA) using
      fluorescent-labeled monoclonal antibodies and flow cytometry. We noted an
      increased expression of activation-dependent antigens on the platelets from
      patients with sickle cell anemia compared with those from both white and black
      control subjects. In addition, patients with sickle cell anemia had increased
      levels of platelet microparticles and PEA. Platelets are activated in patients
      with sickle cell anemia and they adhere to sickle erythrocytes. The significance
      of this activation and adherence are the subject of further investigation.

PMID- 9142048
TI  - A role for Na/K adenosine triphosphatase in the pathogenesis of cyst formation in
      experimental polycystic kidney disease.
AB  - Multiple cyst formation with fluid retention is a characteristic structural
      abnormality in polycystic kidney disease (PKD). Na/K adenosine triphosphatase
      (ATPase) is a major transporting membrane protein that is ubiquitous in the
      epithelial cell, which has been thought to be involved in cystogenesis. We have
      investigated the molecular and histologic basis of Na/K ATPase activity in
      experimental PKD in vivo. Rats were treated with diphenylthiazole (100 mg/100 gm
      body weight), and cyst formation was examined histologically. Na/K ATPase
      activity was measured enzymatically by using a fluorometric method, and reverse
      transcription-competitive polymerase chain reaction (RT-PCR) analysis was used to
      quantitate mRNA levels in the isolated single nephron segment. Kidneys were
      immunostained with subunit-specific antibodies to determine the localization of
      Na/K ATPase in the epithelial cell. The enzyme activity increased in the cortical
      collecting duct from 25.9 +/- 3.5 mmol/Lpmol/mm/min to 72.9 +/- 6.8 pmol/mm/min
      and in the outer medullary collecting duct from 13.0 +/- 3.9 mmol/Lpmol/mm/min to
      58.5 +/- 9.8 pmol/mm/min (n = 6, p < 0.01); however, all other segments showed no
      significant changes. No significant alternation in alpha 1- and beta 1-subunits
      of Na/K ATPase mRNA levels was observed by competitive PCR assay in either
      segment. The enzyme was stained at the basolateral membrane even in the cystic
      tubules. Na/K ATPase activity was up-regulated in the cyst-formed kidney, but
      this was not accompanied with transcriptional up-regulation. Increased Na/K
      ATPase activity at normal locations may play a role in abnormal net fluid
      transport in the development and progression of experimental PKD.

PMID- 9142049
TI  - Surface area and volume changes during maturation of reticulocytes in the
      circulation of the baboon.
AB  - Changes in the surface area and volume of reticulocytes were measured in vivo
      during late stage maturation. Baboons were treated with erythropoietin to produce
      mild reticulocytosis. Reticulocyte-rich cohorts of cells were obtained from whole
      blood by density gradient centrifugation. The cohorts were labeled with biotin,
      reinfused into the animal, and recovered from whole blood samples by panning on
      avidin supports. Changes in the surface area, volume, and membrane deformability
      were measured using micropipettes during the 2 to 6 weeks subsequent to
      reinfusion. For the entire cohort, the membrane area decreased by 10% to 15% and
      the cell volume decreased by approximately 8.5%, mostly within 24 hours after
      reinfusion. Estimates of the cellular dimensions of the reticulocyte
      subpopulation within this cohort indicated larger reductions in the mean cell
      area (12% to 30%) and mean cell volume (approximately 15%) of the reticulocytes
      themselves. Two weeks after reinfusion, the distribution of cell size for the
      cohort was indistinguishable from that of whole blood. There was evidence of
      slightly elevated membrane shear rigidity in some reticulocytes before
      reinfusion, but this slight increase disappeared within 24 hours after
      reinfusion. These are the first direct measurements of changes in the membrane
      physical properties of an identifiable cohort of reticulocytes as they mature in
      vivo.

PMID- 9142050
TI  - Successful brief captopril treatment in experimental radiation nephropathy.
AB  - Experimental renal irradiation is followed by a well-defined sequence of events
      leading to kidney failure. Inhibitors of angiotensin-converting enzyme can
      prevent the structural and functional changes that occur after renal irradiation,
      which suggests that the renin-angiotensin system plays a key role in their
      evolution. We therefore evaluated captopril, used for short intervals, in a total
      body irradiation model of radiation nephropathy. Irradiated 7- to 8-week-old rats
      that were treated with captopril from 3.5 to 9.5 weeks after irradiation had
      better kidney function and survival than irradiated animals treated at earlier or
      later intervals. At 26 weeks after irradiation, kidney function of these animals
      was similar to that of irradiated animals treated continuously with captopril,
      but their subsequent survival was less. Animals irradiated at 7 to 8 weeks of age
      and treated with captopril from 6 to 9 weeks after irradiation had better
      function and survival than animals treated at earlier or later intervals.
      Irradiated 15-week-old animals had significant functional and survival benefit
      from continuous captopril treatment but no protection from a 6-week interval of
      therapy. We conclude that radiation nephropathy may be significantly attenuated
      by the use of captopril from 3.5 to 9.5 weeks after irradiation in young animals.
      Although older animals did not appear to benefit from a short course of
      captopril, these data suggest that the renin-angiotensin system is important in
      the sequential expression of renal radiation injury, particularly between 3.5 and
      9.5 weeks after irradiation.

PMID- 9142051
TI  - Exogenous fatty acids modulate the functional and cytotoxic responses of cultured
      pulmonary artery endothelial cells to oxidant stress.
AB  - We previously reported that supplementation with exogenous fatty acids modulated
      the susceptibility of cultured pulmonary artery endothelial cells (PAEC) to
      oxidant-mediated cytotoxicity. The current study investigates the effects of
      fatty acids with increasing degrees of unsaturation on oxidant-mediated
      dysfunction and cytotoxicity in cultured porcine pulmonary artery and aortic
      endothelial cells (AEC). Monolayers supplemented with 0.1 mmol/L oleic (18:1),
      linoleic (18:2), or gamma-linolenic (18:3) acids were exposed to oxidant stress
      (100 mumol/L hydrogen peroxide (H2O2)) or to control conditions for 30 minutes.
      Gas chromatographic analysis of the PAEC fatty acids confirmed incorporation of
      supplemental fatty acids into PAEC lipids. Cytotoxicity, measured as the release
      of intracellular lactate dehydrogenase (LDH), and PAEC monolayer barrier
      function, assessed by measuring the monolayer clearance of Evans blue dye bound
      to albumin, were determined for 1 to 3 hours after oxidant stress. The PAEC and
      AEC demonstrated comparable responses to H2O2. Hydrogen peroxide caused increases
      in monolayer permeability and detachment of cells from the monolayer that were
      most attenuated by supplementation with 18:2 or 18:3, and to a lesser degree with
      18:1. In contrast, H2O2-mediated LDH release was attenuated by supplementation
      with 18:1, whereas 18:2 and 18:3 potentiated cytotoxicity after exposure to H2O2.
      These results indicate that the relationship between PAEC lipid composition and
      oxidant susceptibility is complex and that the extent of fatty acid unsaturation
      does not predict the functional or cytotoxic responses of PAEC to oxidant stress.
      Furthermore, these results suggest that functional derangements may not correlate
      with traditional assays of cytotoxicity induced by oxidant injury in cultured
      endothelium.

PMID- 9142052
TI  - Role of serotonin in nephrotoxic serum nephritis in WKY rats.
AB  - Our objective was to determine whether serotonin is involved in inducing
      nephrotoxic serum nephritis in WKY rats. After injection of antiglomerular
      basement membrane antiserum, urinary protein excretion was significantly
      decreased in rats treated with the serotonin receptor antagonist, MCI-9042, and
      in rats treated with p-chlorophenylalanine. Similarly, severe necrotizing lesions
      and crescent formation were inhibited in a dose-dependent manner by treatment
      with MCI-9042 and p-chlorophenylalanine. The number of intraglomerular ED-1
      positive cells was increased on day 3 and thereafter in the placebo group. A
      significant increase in the number of crescent lesions was observed in the
      placebo group on day 7 and thereafter. Neither adenosine diphosphate- nor
      collagen-induced platelet aggregations were inhibited in platelet-rich plasma
      from rats treated with MCI-9042. No significant differences were observed in the
      production of circulating antibody and antibody deposition in rat glomeruli among
      the study groups. These results indicate that pathologic changes and urinary
      protein excretion are closely related to the presence of serotonin in nephrotoxic
      serum nephritis of WKY rats. Thus serotonin may play a key role in the glomerular
      injury in this model. Studies on the mode of action of MCI-9042 on platelet
      aggregation in vivo indicate that the antiplatelet effect of this drug did not
      contribute to the inhibition of renal injury in this experimental model. This
      study suggests that serotonin participates in macrophage-mediated immune injury
      in nephrotoxic serum nephritis of WKY rats.

PMID- 9142053
TI  - Stenosis of the tubular neck: a possible mechanism for progressive renal failure.
AB  - Fibrosis in chronic renal failure is closely associated with declining function.
      Its role in affecting function is less well defined. The radiation model of
      chronic renal failure was used to examine the tissue distribution of fibrosis and
      scarring and its role in influencing the loss of function in chronic renal
      disease. A striking and progressive pattern of fibrosis and narrowing of the
      glomerulotubular neck was found in irradiated pig kidneys. These narrowed necks
      increased in prevalence with time after irradiation. At 20 weeks after
      irradiation, the average neck diameter reduction was 60%, as compared with
      nonirradiated controls, a percentage that is consistent with a reduction in flow
      and pressure at this critical point of the nephron. Glomerulotubular neck
      narrowing may thus directly reduce the glomerular filtration rate of an
      individual nephron. Fibrotic neck stenoses may be a factor in progressive chronic
      renal failure.

PMID- 9142054
TI  - From what will we die in 2020?

PMID- 9142055
TI  - Olanzapine: a novel atypical neuroleptic agent.

PMID- 9142056
TI  - Pelvic inflammatory disease in HIV-positive women.

PMID- 9142057
TI  - Activin A, inhibin A, and pre-eclampsia.

PMID- 9142058
TI  - How much to tell parents.

PMID- 9142059
TI  - Dangers of non-sedating antihistamines.

PMID- 9142060
TI  - Mortality by cause for eight regions of the world: Global Burden of Disease
      Study.
AB  - BACKGROUND: Reliable information on causes of death is essential to the
      development of national and international health policies for prevention and
      control of disease and injury. Medically certified information is available for
      less than 30% of the estimated 50.5 million deaths that occur each year
      worldwide. However, other data sources can be used to develop cause-of-death
      estimates for populations. To be useful, estimates must be internally consistent,
      plausible, and reflect epidemiological characteristics suggested by community
      level data. The Global Burden of Disease Study (GBD) used various data sources
      and made corrections for miscoding of important diseases (eg, ischaemic heart
      disease) to estimate worldwide and regional cause-of-death.patterns in 1990 for
      14 age-sex groups in eight regions, for 107 causes. METHODS: Preliminary
      estimates were developed with available vital-registration data, sample
      registration data for India and China, and small-scale population-study data
      sources. Registration data were corrected for miscoding, and Lorenz-curve
      analysis was used to estimate cause-of-death patterns in areas without
      registration. Preliminary estimates were modified to reflect the epidemiology of
      selected diseases and injuries. Final estimates were checked to ensure that
      numbers of deaths in specific age-sex groups did not exceed estimates suggested
      by independent demographic methods. FINDINGS: 98% of all deaths in children
      younger than 15 years are in the developing world. 83% and 59% of deaths at 15-59
      and 70 years, respectively, are in the developing world. The probability of death
      between birth and 15 years ranges from 22.0% in sub-Saharan Africa to 1.1% in the
      established market economies. Probabilities of death between 15 and 60 years
      range from 7.2% for women in established market economies to 39.1% for men in sub
      Saharan Africa. The probability of a man or woman dying from a non-communicable
      disease is higher in sub-Saharan Africa and other developing regions than in
      established market economies. Worldwide in 1990, communicable, maternal,
      perinatal, and nutritional disorders accounted for 17.2 million deaths, non
      communicable diseases for 28.1 million deaths and injuries for 5.1 million
      deaths. The leading causes of death in 1990 were ischaemic heart disease (6.3
      million deaths), cerebrovascular accidents (4.4 million deaths), lower
      respiratory infections (4.3 million), diarrhoeal diseases (2.9 million),
      perinatal disorders (2.4 million), chronic obstructive pulmonary disease (2.2
      million), tuberculosis (2.0 million), measles (1.1 million), road-traffic
      accidents (1.0 million), and lung cancer (0.9 million). INTERPRETATION: Five of
      the ten leading killers are communicable, perinatal, and nutritional disorders
      largely affecting children. Non-communicable diseases are, however, already major
      public health challenges in all regions. Injuries, which account for 10% of
      global mortality, are often ignored as a major cause of death and may require
      innovative strategies to reduce their toll. The estimates by cause have wide Cls,
      but provide a foundation for a more informed debate on public-health priorities.

PMID- 9142061
TI  - Randomised double-blind placebo-controlled study on adverse effects of rubella
      immunisation in seronegative women.
AB  - BACKGROUND: The objective of our study was to investigate the association of
      adverse clinical musculoskeletal and neurological events in healthy postpartum
      women with live attenuated (RA27/3 strain) rubella-virus vaccine, and to assess
      the frequency of acute and recurrent arthralgia and arthritis and associations
      with acute and recurrent muscle pain (myalgia) and neurological manifestations
      (paraesthesias). METHODS: We used a randomised placebo-controlled, double-blind
      design in a community setting. 636 women were enrolled and, after 90 women
      dropped out, 546 healthy women aged 18-41 years, who were rubella seronegative on
      routine screening were immunised parenterally with either monovalent live
      attenuated (RA27/3 strain) rubella vaccine (n = 270) or saline placebo (n = 276)
      in the postpartum period. Outcome measures were the occurrence of acute and
      persistent or recurrent joint manifestations (arthralgia or arthritis) at 1, 3,
      6, 9, and 12 months after immunisation. Occurrence of muscle pain (myalgia), and
      neurological symptoms (paraesthesia) was also assessed at the same times.
      FINDINGS: 543 women completed 1-month follow-up. 456 women completed the 12-month
      assessment. There were no differences at the time of immunisation between rubella
      vaccine and placebo groups in distribution of age, ethnic origin, parity, time
      between delivery and immunisation, breastfeeding history, or histories of earlier
      rubella vaccination or joint complaints. Results indicated a significantly higher
      incidence (p = 0.006; odds ratio = 1.73 [95% CI = 1.17-2.57]) of acute joint
      manifestations in rubella-vaccine recipients (30%) than in placebo recipients
      (20%). Frequency of chronic (recurrent) arthralgia or arthritis was only
      marginally significant (p = 0.042; 1.58 [1.01-2.45]). INTERPRETATION: RA27/3
      rubella vaccine given to seronegative women during the postpartum period was
      significantly associated with development of acute arthralgia or arthritis.
      Although the numbers of women assessed and length of follow-up revealed only
      marginally significant differences in persistent or recurrent joint
      manifestations between rubella vaccine and placebo recipients, it is possible
      that susceptible women who are given rubella vaccination may experience this
      outcome.

PMID- 9142062
TI  - Depression and cognitive decline after coronary artery bypass grafting.
AB  - BACKGROUND: Depression is commonly reported after coronary artery bypass grafting
      (CABG), and after cardiac surgery in general. Many earlier reports relied on non
      standard assessments of depression, which may have overestimated its frequency.
      Cognitive decline has also been reported after CABG. We assessed the frequency of
      depression after CABG by a validated depression measure (Center for
      Epidemiological Study of Depression, CES-D), and examined the relation between
      depression and cognitive decline. METHODS: Patients were tested before CABG and 1
      month and 1 year after surgery with a series of neuropsychological tests that
      assessed a range of cognitive areas. Depressed mood was measured by the CES-D
      scale, and defined as a score above 16. FINDINGS: 90 (73%) of the 124 patients
      were not depressed before surgery, and 34 were depressed at that time. Only 12
      (13%) of patients not depressed before surgery were depressed at 1 month
      afterwards, whereas 18 (53%) of those who were depressed before surgery were
      depressed at 1 month (p < 0.001). 8 (9%) patients not depressed before surgery
      were depressed at 1 year; 16 (47%) of patients who were depressed before CABG
      were depressed at 1 year (p < 0.001). Statistical analysis showed only minimal
      correlation-or none at all-between depression and eight areas of cognitive
      outcome, or between changes in depressed status and cognitive scores.
      INTERPRETATION: Of those patients who were depressed after CABG, the large
      majority were depressed before surgery. There was no correlation, moreover,
      between depressed mood and cognitive decline after CABG, which suggests that
      depression alone cannot account for cognitive decline.

PMID- 9142063
TI  - Activin A and inhibin A as possible endocrine markers for pre-eclampsia.
AB  - BACKGROUND: Inhibin A and activin A are produced by the placenta during human
      pregnancy. This study aimed to measure circulating concentrations of inhibin A,
      pro alpha C-containing inhibins, and activin A in the serum of women with pre
      eclampsia and of healthy matched control pregnant women, and to establish the
      molecular-weight forms of circulating inhibin A and activin A in pre-eclampsia.
      METHODS: In a retrospective cross-sectional study, blood samples were taken from
      20 women in hospital with established pre-eclampsia, and from 20 control pregnant
      women attending antenatal clinics, who were matched for duration of gestation
      (pre-eclampsia mean 29.15 [SD 3.75] weeks; controls 29.30 [3.93] weeks), parity,
      and maternal age. Serum samples were analysed for inhibin A, inhibin B, pro alpha
      C, and activin A. Pooled samples of control (n = 3) and pre-eclampsia serum (n =
      3) subsequently underwent fast protein liquid chromatographic analysis to assess
      the molecular-weight forms of inhibin A and activin A. Results are expressed as
      mean and SD for all variables measured. FINDINGS: Serum concentrations of inhibin
      A, activin A, and pro alpha C were significantly higher in pre-eclampsia than in
      control normal pregnancy (inhibin A 3.05 [1.8] vs 0.36 [0.14] ng/mL, p < 0.001;
      activin A 38.08 [25.88] vs 3.95 [2.32] ng/mL, p < 0.001; pro alpha C-containing
      inhibins 2.2 [0.81] vs 0.71 [0.33] ng/mL, p < 0.001). Inhibin B concentrations in
      maternal serum were not increased. Molecular-weight forms of inhibin A (32 kDa)
      and activin A (> 100 kDa) were similar in pre-eclampsia and normal pregnancy. The
      mean concentrations of hCG were 59.05 [43.98] and 16.3 [8.72] ng/mL,
      respectively. INTERPRETATION: Higher maternal serum concentrations of inhibin A,
      pro alpha C, and total activin A in pre-eclampsia than in control pregnancies
      could be helpful in the diagnosis of pre-eclampsia. These changes are interpreted
      as further evidence for trophoblast dysfunction in pre-eclampsia.

PMID- 9142064
TI  - Preliminary assessment of three-dimensional magnetic resonance imaging for
      various colonic disorders.
AB  - BACKGROUND: Improvements in magnetic resonance imaging (MRI) technology have
      enabled the acquisition of three-dimensional MRI datasets in a single breath
      hold. We adopted this technique to make a three dimensional intraluminal and
      extraluminal assessment of the colon in three patients with various colonic
      disorders. METHODS: One patient was studied after having a double-contrast barium
      enema. Two patients had MRI scans after colonoscopy, which showed three colonic
      tumours in one and multiple polyps in the ascending colon of the other. The
      process of rectal filling with 1.5-2.0 L water mixed with 15-20 mL 0.5 mol/L
      gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) was monitored with MR
      fluoroscopic sequence. Three-dimensional datasets of the contrast-filled colon
      were taken with patients in prone (before and after intravenous administration of
      0.1 mmol/kg bodyweight Gd-DTPA) and supine positions. 64 sections with a voxel
      resolution of 2.0 x 2.0 x 1.25 mm3-were taken during a 28 s breath hold. Three
      dimensional maximum intensity projection, multiplanar reconstruction, and virtual
      colonoscopic images of the colon were created from these. FINDINGS: Analysis of
      the coronal source images in conjunction with multiplanar reconstructions
      revealed all relevant abnormalities, including diverticula, carcinomas, and
      polyps. Three dimensional maximum-intensity projections gave a morphological
      overview of the whole colon. Targeted projections, made up of a limited number of
      coronal source images, showed diverticula and smaller polyps more clearly. After
      patients were given intravenous contrast all colonic mass lesions were enhanced.
      Datasets obtained in prone patients gave the best intraluminal views of the
      colon. Virtual magnetic resonance colonoscopy showed colonic haustra as well as
      the ileocaecal valve, but did not show clearly the diverticula. All intraluminal
      mass lesions, on the other hand, were easy to see. INTERPRETATION: The potential
      of three-dimensional colonic MRI to provide accurate, minimally invasive, cost
      effective polyp screening, as well as comprehensive colonic tumour staging,
      warrants further investigation.

PMID- 9142065
TI  - Angina for 14 years.

PMID- 9142066
TI  - Effect of granisetron on cholera toxin-induced enteric secretion.

PMID- 9142067
TI  - Decline in deaths from AIDS due to new antiretrovirals.

PMID- 9142068
TI  - Urinary stones in HIV-1-positive patients treated with indinavir.

PMID- 9142069
TI  - Improved oxygen delivery by positive pressure ventilation with continuous
      negative external chest pressure.

PMID- 9142070
TI  - Effect on vision of binocular foveal contour interactions.

PMID- 9142071
TI  - Molecular studies of haemoglobin-E in tribal populations of Tripura.

PMID- 9142072
TI  - Heat-related mortality among nursing-home patients.

PMID- 9142073
TI  - Gynaecomastia in onchocerciasis.

PMID- 9142075
TI  - USA accused of funding placebo-controlled AIDS trials.

PMID- 9142076
TI  - The natriuretic-peptide family.

PMID- 9142077
TI  - Asbestosis and silicosis.
AB  - Interstitial fibrosis resulting from workplace exposure to asbestos and
      crystalline silica persists throughout the world despite knowledge of the causes
      and effective means for prevention. Asbestosis and silicosis occurrence is
      predictable among people overexposed to dusts in various industries and
      occupations such as mining, construction, manufacturing, and building
      maintenance. Asbestosis and silicosis are incurable and may be progressive even
      after dust exposure has ceased, therefore early recognition and supportive
      interventions are important. Although current disease is a result of past
      exposures, effective control of current workplace exposures is the only way to
      prevent continued occurrence of these potentially debilitating diseases.
      Physicians can contribute to this effort through accurate diagnosis and disease
      reporting.

PMID- 9142079
TI  - Science in a health service.

PMID- 9142078
TI  - The history of pulp and paper bleaching: respiratory-health effects.

PMID- 9142080
TI  - Risks of non-sedating antihistamines.

PMID- 9142081
TI  - Diagnosis of new variant Creutzfeldt-Jakob disease by tonsil biopsy.

PMID- 9142082
TI  - Diagnosis of new variant Creutzfeldt-Jakob disease by tonsil biopsy.

PMID- 9142083
TI  - Laparoscopic surgery.

PMID- 9142084
TI  - Laparoscopic surgery.

PMID- 9142085
TI  - Laparoscopic surgery.

PMID- 9142086
TI  - Carotid and Vertebral Artery Transluminal Angioplasty Study.

PMID- 9142087
TI  - Randomised controlled trial of hydroquinine in muscle cramps.

PMID- 9142088
TI  - Randomised controlled trial of hydroquinine in muscle cramps.

PMID- 9142089
TI  - Randomised controlled trial of hydroquinine in muscle cramps.

PMID- 9142090
TI  - Digoxin concentrations in Indian patients.

PMID- 9142091
TI  - Blood donations and viruses.

PMID- 9142092
TI  - Blood donations and viruses.

PMID- 9142093
TI  - Severe encephalitis with rapid recovery.

PMID- 9142094
TI  - Cyclosporin in Crohn's disease.

PMID- 9142095
TI  - Support for UK biomedical research from tobacco industry.

PMID- 9142096
TI  - Support for UK biomedical research from tobacco industry.

PMID- 9142097
TI  - Illicit drugs for medical use.

PMID- 9142098
TI  - The rise and rise of evidence-based medicine.

PMID- 9142099
TI  - White-coat hypertension triggered by iatrogenic hypertension.

PMID- 9142101
TI  - Basic science and better medicine.

PMID- 9142100
TI  - Sealing the fate of HIV.

PMID- 9142102
TI  - Progress on blood substitutes.

PMID- 9142103
TI  - Neuronal xenotransplantation in Parkinson's disease.

PMID- 9142104
TI  - Animal models of psoriasis.

PMID- 9142105
TI  - Guilty pleas intensify row over contaminated blood.

PMID- 9142106
TI  - Gene therapy gets the green light in Japan.

PMID- 9142107
TI  - How immune-based interventions can change HIV therapy.

PMID- 9142109
TI  - Human TSE disease--viral or protein only?

PMID- 9142108
TI  - T-cell homeostasis in HIV infection is neither failing nor blind: modified cell
      counts reflect an adaptive response of the host.

PMID- 9142110
TI  - Estrogen receptor beta--getting in on the action?

PMID- 9142111
TI  - A sensitive defense: salt and cystic fibrosis.

PMID- 9142112
TI  - Chromosomal breakpoints hit the spot.

PMID- 9142113
TI  - Neurotrophic factor therapy--keeping score.

PMID- 9142114
TI  - Cleaning up on beta-catenin.

PMID- 9142115
TI  - DNA vaccination for HIV.

PMID- 9142116
TI  - A role for nitric oxide synthase in urinary "urge syndrome".

PMID- 9142117
TI  - Cancer dormancy: opportunities for new therapeutic approaches.

PMID- 9142118
TI  - Sunlight and skin cancer: inhibition of p53 mutations in UV-irradiated mouse skin
      by sunscreens.
AB  - UV-induced mutations in the p53 tumor suppressor gene play an essential role in
      skin cancer development. We report here that such mutations can be detected in UV
      irradiated mouse skin months before the gross appearance of skin tumors.
      Application of SPF-15 sunscreens to mouse skin before each UV irradiation nearly
      abolished the frequency of p53 mutations. These results indicate that p53
      mutation is an early event in UV skin carcinogenesis and that inhibition of this
      event may serve as an early end point for assessing protective measures against
      skin cancer development.

PMID- 9142119
TI  - Targeting gene expression to hypoxic tumor cells.
AB  - Solid tumors with areas of low oxygen tension (hypoxia) have a poor prognosis, as
      cells in this environment often survive radiation and chemotherapy. In this
      report we describe how this hypoxic environment can be used to activate
      heterologous gene expression driven by a hypoxia-responsive element (HRE), which
      interacts with the transcriptional complex hypoxia-inducible factor-1 (HIF-1).
      Our results demonstrate that the HIF-1/HRE system of gene regulation is active in
      hypoxic tumor cells and show the potential of exploiting tumor-specific
      conditions for the targeted expression of diagnostic or therapeutic genes in
      cancer therapy.

PMID- 9142120
TI  - Identification of the prion protein allotypes which accumulate in the brain of
      sporadic and familial Creutzfeldt-Jakob disease patients.
AB  - A characteristic feature of Creutzfeldt-Jakob disease (CJD) is the accumulation
      in the brain of the amyloid protease-resistant protein PrPres. PrPres derives
      from a host-encoded, protease-sensitive isoform, PrPsen. Mutations of this
      protein are linked to familial variants of the disease, and the presence of a
      methionine or valine residue at the polymorphic position 129 may be critical in
      sporadic CJD cases. We found that in the brain of patients heterozygous for the
      mutation in which isoleucine is substituted for valine at codon 210 (Val21Olle),
      the PrPres is formed by both the wild-type and mutant PrPsen. We also found that
      in a sporadic CJD patient, who was heterozygous (Met/Val) at position 129, PrPres
      is also formed by both allotypes. These data associate transmissible spongiform
      encephalopathies with other amyloidosis, although the nature of the transmissible
      agent remains unsettled.

PMID- 9142121
TI  - Protection of chimpanzees from high-dose heterologous HIV-1 challenge by DNA
      vaccination.
AB  - Novel approaches for the generation of more effective vaccines for HIV-1 are of
      significant importance. In this report we analyze the immunogenicity and efficacy
      of an HIV-1 DNA vaccine encoding env, rev and gag/pol in a chimpanzee model
      system. The immunized animals developed specific cellular and humoral immune
      responses. Animals were challenged with a heterologous chimpanzee titered stock
      of HIV-1 SF2 virus and followed for 48 weeks after challenge. Polymerase chain
      reaction coupled with reverse transcription (RT-PCR) results indicated infection
      in the control animal, whereas those animals vaccinated with the DNA constructs
      were protected from the establishment of infection. These studies serve as an
      important benchmark for the use of DNA vaccine technology for the production of
      protective immune responses.

PMID- 9142122
TI  - HIV infection induces changes in CD4+ T-cell phenotype and depletions within the
      CD4+ T-cell repertoire that are not immediately restored by antiviral or immune
      based therapies.
AB  - Changes in CD4+ T-cell surface marker phenotype and antigen receptor (TCR)
      repertoire were examined during the course of HIV infection and following
      therapy. A preferential decline in naive CD4+ T cells was noted as disease
      progressed. Following protease inhibitor therapy, naive CD4+ T cells increased
      only if they were present before initiation of therapy. Disruptions of the CD4+
      TCR repertoire were most prevalent in patients with the lowest CD4+ T-cell
      counts. Antiviral or IL-12 therapy-induced increases in CD4+ T-cell counts led to
      only minor changes in previously disrupted repertoires. Thus, CD4+ T-cell death
      mediated by HIV-1 infection may result in a preferential decline in the number of
      naive CD4+ T cells and disruptions of the CD4+ T-cell repertoire that are not
      immediately corrected by antiviral or immune-based therapies.

PMID- 9142123
TI  - A homologue of Drosophila tissue polarity gene frizzled is expressed in migrating
      myofibroblasts in the infarcted rat heart.
AB  - Myocardial infarction results in the formation of granulation tissue in the
      injured ventricular wall. This tissue contains myofibroblasts in highly organized
      arrays; their contractile properties may help to prevent the infarct area from
      dilatation. The mechanisms that control myofibroblast alignment are unknown. We
      found that myofibroblasts express a homologue of Drosophila tissue polarity gene
      frizzled (fz2) when migrating into the granulation tissue. The expression is
      decreased after the cells have aligned. This suggests that fz2 is involved in the
      spatial control of cardiac wound repair after infarction, possibly through intra-
      and intercellular transmission of polarity signals as in developing Drosophila.
      Mutations in the fz2 gene may impair myofibroblast alignment in the infarct area,
      thereby resulting in ventricular dilatation and aneurism following infarction.

PMID- 9142124
TI  - Estrogen inhibits the vascular injury response in estrogen receptor alpha
      deficient mice.
AB  - The atheroprotective effects of estrogen in women are well recognized, but the
      underlying mechanisms responsible are not well understood. Blood vessel cells
      express the classic estrogen receptor, ER alpha (ref. 2-6), and are directly
      affected by estrogen, which inhibits the development of atherosclerotic and
      injury-induced vascular lesions. We have generated mice in which the ER alpha
      gene is disrupted and have used a mouse model of carotid arterial injury to
      compare the effects of estrogen on wild-type and estrogen receptor-deficient
      mice. Increases in vascular medial area and smooth muscle cell proliferation were
      quantified following vascular injury in ovariectomized mice treated with vehicle
      or with physiologic levels of 17 beta-estradiol. Surprisingly, in both wild-type
      and estrogen receptor-deficient mice, 17 beta-estradiol markedly inhibited to the
      same degree all measures of vascular injury. These data demonstrate that estrogen
      inhibits vascular by a novel mechanism that is independent of the classic
      estrogen receptor, ER alpha.

PMID- 9142125
TI  - Maternal HIV-1 viral load and vertical transmission of infection: the Ariel
      Project for the prevention of HIV transmission from mother to infant.
AB  - Most HIV-1 infections of children result from mother-to-infant transmission,
      which may occur perinatally or postnatally, as a consequence of breast feeding.
      In this study, the influence of maternal viral load on transmission of infection
      to infants from non-breast-feeding mothers was examined using samples of plasma
      and peripheral blood mononuclear cells (PBMCs) collected at several time points
      during pregnancy and the 6-month period after delivery. These samples were
      analyzed by several quantitative methods, including virus cultures of PBMCs and
      polymerase chain reaction (PCR) assays for HIV-1 RNA in plasma and DNA in PBMCs.
      The risk of transmission increased slightly with a higher viral load, but
      transmission and nontransmission occurred over the entire range of values for
      each assay. No threshold value of virus load was identified which discriminated
      between transmitters and nontransmitters. We also noted a significant rise in
      viral load and a decline in CD4+ lymphocytes in the six months after delivery.
      These findings suggest that a high maternal viral load is insufficient to fully
      explain vertical transmission of HIV-1. Additional studies are needed to examine
      the post-partum increase in viremia.

PMID- 9142126
TI  - Empirical evidence for the severe but localized impact of AIDS on population
      structure.
AB  - Despite considerable speculation on the demographic impact of AIDS, there has
      been, until now, little scientific evidence to establish its existence or scale.
      Because of the widespread implications of these predictions, methods to combine
      demography and epidemiology to study empirical situations have been an urgent
      priority. This study derives the extent and mechanisms of demographic impacts of
      AIDS from routine data (the 1991 census) in a severely affected country, Uganda.
      Three characteristics are of particular note: first, the emergence of demographic
      impacts much earlier than previously estimated; second, their localization with
      negative population growth at parish but not at district or national scales;
      third, a greater impact on the number of children than previously predicted, due
      as much to changes in population fertility as mortality. The emergence of
      demographic impacts at this stage highlights original aspects of the
      interdependence of HIV infection and demographic growth not previously recorded
      and the need to target preventive interventions to youth in developing countries.

PMID- 9142127
TI  - Induction of antitumor activity by immunization with fusions of dendritic and
      carcinoma cells.
AB  - Dendritic cells (DCs) are potent antigen-presenting cells that prime naive
      cytotoxic T-cells (CTLs). In this study, we have fused DCs with MC38 carcinoma
      cells. The fusion cells were positive for major histocompatibility (MHC) class I
      and II, costimulating molecules and intercellular cell adhesion molecule-1 (ICAM
      1). The results show that the fusion cells stimulate naive T cells in the primary
      mixed lymphocyte reaction (MLR) and induce MC38 tumor-specific CTLs in vivo.
      Antibody-mediated depletion experiments demonstrate that induction of CD4+ and
      CD8+ CTLs protects against challenge with tumor cells. We also show that
      immunization with the fusion cells induces rejection of established metastases.
      These findings represent the first demonstration that fusions of DCs and tumor
      cells can be used in the treatment of cancer.

PMID- 9142128
TI  - Bioactivation of leukotoxins to their toxic diols by epoxide hydrolase.
AB  - Leukotoxin is a linoleic acic oxide produced by leukocytes and has been
      associated with the multiple organ failure and adult respiratory distress
      syndrome seen in some severe burn patients. Leukotoxin has been reported to be
      toxic when injected into animals intravenously. Herein, we report that this lipid
      is not directly cytotoxic in at least two in vitro systems. Using a baculovirus
      expression system we demonstrate that leukotoxin is only cytotoxic in the
      presence of epoxide hydrolases. In addition, it is the diol metabolite that
      proves toxic to pulmonary alveolar epithelial cells, suggesting a critical role
      for the diol in leukotoxin-associated respiratory disease. In vivo data also
      support the toxicity of leukotoxin diol. For the first time we demonstrate that
      soluble epoxide hydrolase can bioactivate epoxides to diols that are apparently
      cytotoxic. Thus leukotoxin should be regarded as a protoxin corresponding to the
      more toxic diol. This clearly has implications for designing new clinical
      interventions.

PMID- 9142129
TI  - The emb operon, a gene cluster of Mycobacterium tuberculosis involved in
      resistance to ethambutol.
AB  - Ethambutol (EMB), a frontline antituberculous drug, targets the mycobacterial
      cell wall, a unique structure among prokaryotes which consists of an outer layer
      of mycolic acids covalently bound to peptidoglycan via the arabinogalactan. EMB
      inhibits the polymerization of cell wall arabinan, and results in the
      accumulation of the lipid carrier decaprenol phosphoarabinose, which suggests
      that the drug interferes with the transfer of arabinose to the cell wall
      acceptor. Unfortunately, resistance to EMB has been described in up to 4% of
      clinical isolates of Mycobacterium tuberculosis and is prevalent among isolates
      from patients with multidrug-resistant tuberculosis. We used resistance to EMB as
      a tool to identify genes participating in the biosynthesis of the mycobacterial
      cell wall. This approach led to the identification of the embCAB gene cluster,
      recently proposed to encode for mycobacterial arabinosyl transferases. Resistance
      to EMB results from an accumulation of genetic events determining overexpression
      of the Emb protein(s), structural mutation in EmbB, or both. Further
      characterization of these proteins might provide information on targets for new
      chemotherapeutic agents and might help development of diagnostic strategies for
      the detection of resistant M. tuberculosis.

PMID- 9142130
TI  - Urinary bladder-urethral sphincter dysfunction in mice with targeted disruption
      of neuronal nitric oxide synthase models idiopathic voiding disorders in humans.
AB  - Idiopathic voiding disorders affect up to 10-15% of men and women. We describe
      bladder abnormalities in mice with targeted deletion of the gene for neuronal
      nitric oxide synthase which model the clinical disorders. The mice possess
      hypertrophic dilated bladders and dysfunctional urinary outlets which do not
      relax in response to electrical field stimulation or L-arginine. The mice also
      display increased urinary frequency.

PMID- 9142131
TI  - Human leptin levels are pulsatile and inversely related to pituitary-adrenal
      function.
AB  - Leptin communicates nutritional status to regulatory centers in the brain.
      Because peripheral leptin influences the activity of the highly pulsatile adrenal
      and gonadal axes, we sought to determine whether leptin levels in the blood are
      pulsatile. We measured circulating leptin levels every 7 minutes for 24 hours, in
      six healthy men, and found that total circulating leptin levels exhibited a
      pattern indicative of pulsatile release, with 32.0 +/- 1.5 pulses every 24 hours
      and a pulse duration of 32.8 +/- 1.6 minutes. We also show an inverse relation
      between rapid fluctuations in plasma levels of leptin and those of
      adrenocorticotropic hormone (ACTH) and cortisol that could not be accounted for
      on the basis of glucocorticoid suppression of leptin. As leptin levels are
      pulsatile, we propose that a key function of the CNS is regulated by a peripheral
      pulsatile signal. In a separate pilot study we compared leptin pulsatility in 414
      plasma samples collected every 7 minutes for 24 hours from one obese woman and
      one normal-weight woman. We found that high leptin levels in the obese subject
      were due solely to increased leptin pulse height; all concentration-independent
      pulsatility parameters were almost identical in the two women. Leptin pulsatility
      therefore can be preserved in the obese.

PMID- 9142132
TI  - Gel microdrop technology for rapid isolation of rare and high producer cells.
AB  - Secreted proteins are a therapeutic cornerstone of the biotechnology industry,
      and numerous recombinant products, including human growth hormone, human
      erythropoietin and granulocyte-colony stimulating factor, are now widely
      prescribed. In addition to bioprocessing applications, GMD technology should
      benefit the emerging fields of cellular and gene therapy. The ability to assess
      rapidly and precisely the productivity of cells for ex vivo cell screening and
      expansion is a unique approach with numerous research and therapeutic uses.

PMID- 9142133
TI  - Corticotropin-releasing factor (CRF) and endocrine responses to stress: CRF
      receptors, binding protein, and related peptides.
AB  - Corticotropin-releasing factor (CRF) is a 41-amino acid neuropeptide, which is
      recognized as a critical mediator of complimentary, stress-related endocrine,
      autonomic, and behavioral responses in mammalian species. CRF belongs to a family
      of structurally related peptides including frogskin sauvagine and fish urotensin
      I. The effects of CRF and related peptides are mediated by two distinct
      receptors, which differ in their anatomical distribution, as well as in their
      pharmacological characteristics. In addition, CRF is bound with high affinity by
      a CRF binding protein (CRF-BP), which is a putative inhibitor of CRF action. CRF
      is probably not the sole endogenous ligand for CRF receptors or the CRF-BP, since
      a second mammalian member of the CRF family, urocortin, has recently been
      identified. This article describes recent findings with respect to CRF, its
      receptors, binding protein, and CRF-related peptides, which provide further
      insights into the role and mechanisms of CRF action in stress responses.

PMID- 9142134
TI  - Th1 and Th2 CD4+ cells in the pathogenesis of allergic diseases.
AB  - Our understanding of the molecular and genetic etiologies of allergic disorders,
      which affect 20%-30% of the general population, has greatly improved over the
      past several years. Previously, research focused on examination of immediate
      hypersensitivity reactions, initiated by the cross-linking of IgE molecules on
      the surface of mast cells/basophils, resulting in the release of a host of
      mediators, which cause symptoms typified by acute anaphylaxis. Although there has
      been substantial progress in understanding the molecular biology of mast cell and
      basophil activation and of the regulation of IgE synthesis, recent studies have
      shifted attention to the cellular and molecular mechanisms that cause a broader
      allergic inflammatory response and underlie the more chronic and severe symptoms
      of allergy and asthma. In this report, we will review a substantial body of
      recent experimental work that has provided the basis for our new understanding of
      the allergic inflammatory response and the pathogenesis of allergic diseases. We
      will describe the recent progress in defining the immunological basis for
      allergic disease, and how subsets of helper CD4+ T cells secreting a specific
      array of cytokines (Th2 cytokines) regulate/cause allergic inflammation. We will
      review the cell biology of Th2 cells, the role of Th2 cells in allergic disease,
      and biological, genetic, and therapeutic mechanisms that influence the
      differentiation of CD4+ T cells and enhance or suppress cytokine synthesis in Th2
      cells. These mechanisms control the expression of allergic diseases, which occur
      in some but not all individuals following environmental exposure to allergens.

PMID- 9142135
TI  - Ocular actions of endothelins.

PMID- 9142136
TI  - Molecular actions of prolactin in the immune system.
AB  - The immunoregulatory properties of prolactin, a pituitary peptide hormone, have
      received renewed attention. The prolactin receptor, a member of the
      hematopoietin/cytokine receptor superfamily, is ubiquitously expressed by cells
      in the immune system. Certain subpopulations of lymphocytes synthesize and
      secrete biologically active prolactin, which suggests that prolactin can act as
      an autocrine and/or paracrine factor to modulate the activities of cells of the
      immune system. This review focuses on the molecular actions of prolactin in the
      immune system. Emphasis is given to recent information about the molecular
      mechanisms of prolactin receptor signal transduction, and the signaling molecules
      and prolactin-inducible target genes that participate in these responses. In
      particular, the prolactin-inducible interferon regulatory factor-1 gene and its
      roles in mediating diverse immune responses are highlighted.

PMID- 9142137
TI  - Effect of polydextrose on absorption of triglyceride and cholesterol in
      mesenteric lymph-fistula rats.
AB  - In most experimental designs, the inhibitory effect of water-soluble dietary
      fibers on lipid absorption is evaluated by the decrease in plasma lipid
      concentration or the increase in fecal lipid output. The aim of this study was to
      evaluate the acute effect of a water-soluble polysaccharide, polydextrose, on
      lipid transport to the mesenteric lymph using lymph-fistula rats. The mesenteric
      lymph duct of rats was cannulated, and an infusion tube was introduced into the
      duodenum. After recovery, a lipid emulsion containing radioactive triolein and
      cholesteryl oleate was infused into the duodenum for 8 hr. The tested group was
      infused with the lipid emulsion containing 5% or 10% polydextrose as dietary
      fiber. Samples from the lymph-fistula were collected, and the luminal contents
      and mucosa were collected at the end of infusion. Lymph flow in the mesenteric
      lymph decreased in the polydextrose group after the infusion. The amounts of both
      triglyceride and cholesterol remaining in the lumen were greater in the
      polydextrose group, due to decreased transport of lipid into the lymph. These
      effects were dose dependent in the 5% and 10% polydextrose groups. The results of
      this study indicate that polydextrose retarded the transport of triolein and
      cholesterol into the mesenteric lymph.

PMID- 9142138
TI  - Cultured human uterine smooth muscle cells are retinoid responsive.
AB  - Primary cultures of human uterine smooth muscle cells have been widely used as a
      model system to evaluate agents that may play a role in the regulation of both
      normal and abnormal proliferative responses. We have used this in vitro system to
      determine if human uterine smooth muscle cells are responsive to treatment with a
      potent natural derivative of vitamin A, all-trans retinoic acid (ATRA). These
      studies were also designed to determine if there is a difference in retinoid
      responsiveness between normal smooth muscle and adjacent leiomyoma (a benign
      tumor of uterine smooth muscle). When cells were cultured in the presence of
      ATRA, a dose-dependent inhibition in proliferation was observed. This inhibition
      in proliferation was accompanied by an alteration in smooth muscle cell
      morphology. Both the inhibition in proliferation and the altered morphology were
      reversible when ATRA treatment was discontinued. Responsiveness to retinoids is
      determined, in part, by the expression of ligand-specific receptors belonging to
      the steroid/thyroid superfamily (RARs and RXRs); we have therefore identified the
      pattern of retinoid receptor transcript expression in human uterine smooth muscle
      cells. The data indicate that human uterine smooth muscle cells express retinoic
      acid receptors RAR alpha, beta, and gamma, and retinoid X receptors RXR alpha and
      beta. No difference in retinoid responsiveness or in the pattern of retinoid
      receptor expression was observed between normal smooth muscle and adjacent
      leiomyoma. This is the first observation of an antiproliferative effect of ATRA
      in uterine smooth muscle cells and the first report of retinoid receptor
      expression patterns in this cell type. Since retinoids are common pharmacologic
      tools in the treatment of a wide variety of hyperproliferative disorders, these
      observations may have both therapeutic and toxicologic implications.

PMID- 9142139
TI  - Novel activation of gamma-interferon in nonimmune cells during human
      cytomegalovirus replication.
AB  - This is the first study documenting the induction of gamma-interferon (IFN-gamma)
      in human embryonic fibroblasts during human cytomegalovirus (HCMV) replication.
      Infection of cells with HCMV resulted in the consistent production of IFN-gamma
      RNA, as determined by RT-PCR and Northern blot analysis. Western blot analysis of
      cell lysates and immunoprecipitates from the cultural fluids of infected cells
      demonstrated the presence of IFN-gamma at the protein level. Induction of IFN
      gamma required infectious HCMV, since high-dose ultraviolet inactivation of the
      virus stock eliminated IFN-gamma production. Further, IFN-gamma induction appears
      to be a late event in the virus replication cycle, since inhibition of HCMV DNA
      synthesis (e.g., phosphonoacetic acid) blocked the increase in IFN-gamma. Soluble
      factor(s) released from HCMV-infected cells apparently did not contribute to the
      induction of IFN-gamma, since virus stocks from which virus had been removed by
      sedimentation did not induce production of IFN-gamma. The appearance of IFN-gamma
      at late stages of HCMV infection and its elimination in the presence of an
      inhibitor (Actinomycin D) of RNA synthesis indicate a true transcriptional
      induction of this lymphokine at the RNA and protein levels. The significance of
      IFN-gamma production with regard to the replication and pathogenesis of HCMV in
      vitro and in vivo will require further investigation.

PMID- 9142140
TI  - Modulation of the testicular steroidogenic pathway by cyclosporin A in adult rats
      pretreated with diethylstilbestrol.
AB  - Treatment of male Fischer-344 rats with diethylstilbestrol (DES) induces
      hyperprolactinemia and alterations in testicular steroidogenesis. Cyclosporin A
      (CsA), an immunosuppressive drug, is believed to act by opposing the effects of
      prolactin (PRL) and was reported to influence testicular function. We have
      examined the effect of CsA on gonadal function in rats pre-treated with DES. Male
      rats were implanted with DES-containing silastic capsules. After 19 weeks, the
      capsules were removed, and, starting 2.5 weeks later, rats were treated for 1
      week with CsA. At sacrifice, plasma and testes were collected. Testis fragments
      were incubated with or without 12.5 mlU of human chorionic gonadotropin (hCG)/ml
      at 32 degrees C for 4 hr. As expected, plasma PRL levels were increased in DES
      exposed rats, while testicular, seminal vesicle, and prostate weights were
      reduced. Cyclosporin A treatment did not further modify these parameters.
      Treatment with CsA and/or DES decreased circulating levels of testosterone, while
      testosterone content in the testes was not modified. Although CsA did not affect
      in vitro release of testosterone, it reduced the stimulatory influence of DES
      pretreatment on testicular responses to hCG in vitro. Plasma and testicular
      content of progesterone (P) was increased by DES administration but was not
      affected by CsA. Both CsA and DES administration decreased plasma 17-OH
      Progesterone (17-OH-P) levels, but only CsA decreased testicular 17-OH-P
      contents. Combined exposure to CsA and DES enhanced the stimulatory effect of hCG
      on the accumulation of 17-OH-P in the media. Media estradiol levels were not
      affected by treatment with either CsA or DES. The present results indicate that
      CsA may interfere with the enhancement of the conversion of P to testosterone in
      DES-treated rats. As CsA did not change plasma PRL or gonadotropin levels, a
      direct effect of the drug on the testicular function is suspected.

PMID- 9142141
TI  - Dietary carbohydrate and fat do not alter the thyroid response to protein
      deficiency in chicks.
AB  - Consumption of low-protein diets consistently causes elevations in circulating
      levels of triiodothyronine (T3) in several species of animals. In chicks this is
      often accompanied by lower levels of circulating thyroxine (T4). Since low
      protein diets are usually formulated by replacing the detected protein with
      carbohydrate, the question arises as to whether the changes in thyroid hormones
      are a result of the lower protein or higher amounts of carbohydrate in such
      diets. Male broiler chicks, 13-26 days of age, were fed experimental diets that
      contained either an adequate level of protein (24%) or levels that were slightly
      (17%) or moderately (10%) deficient in protein. The deleted protein was replaced,
      isocalorically, with either glucose, soybean oil, or hydrogenated coconut fat.
      Though the level of protein and source of energy differed among diets, all diets
      contained identical amounts of all nutrients and energy, and were of similar
      weight densities. Circulating levels of thyroid hormones were measured from blood
      samples taken at the end of the study. Plasma T3 was elevated to a similar degree
      in all protein-deficient animals compared with control. Plasma T4 decreased in
      all protein-deficient chicks and was lowest with 10% dietary protein. Changes in
      circulating levels of thyroid hormones occurred independently of the source of
      dietary energy. Therefore, it is concluded that alterations in circulating levels
      of thyroid hormones that occur in chicks fed low-protein diets are a specific
      effect of the protein deficit and are not a related to the amounts of
      carbohydrate or fat present in the diet.

PMID- 9142142
TI  - Cocaine inhibits production of murine hepatitis virus by peritoneal macrophages
      in vitro.
AB  - Our previous studies have demonstrated a number of effects of cocaine on
      macrophage (M phi) functions. The present studies were initiated to ascertain the
      effects of cocaine on virus production in vitro. C57BL/6 mice were injected
      intraperitoneally with thioglycollate broth, and the peritoneal M phi collected 4
      days later were cultured in 96-well microtiter plates as continuous monolayers.
      Various concentrations of cocaine were incubated with M phi for up to 5 days.
      Mouse hepatitis virus (MHV) was added to these cultures, which was followed by a
      methyl cellulose overlay. Cocaine caused a dose-dependent inhibition of viral
      plaques after 48 hr of incubation. The inhibitory activity was transferable to
      fresh cultures of M phi, inhibiting both plaque size and number. Specific
      polyclonal antibodies to alpha + beta-interferon but not tumor necrosis factor or
      transforming growth factor-beta partially reversed the inhibition of both plaque
      size and plaque number. It appears that MHV induced interferon in cultured M phi,
      an effect that was enhanced by cocaine. Since cocaine has been reported to
      interfere with calcium mobilization, studies were done using ionomycin, a calcium
      ionophore, in order to reverse possible effects on intracellular calcium that
      could affect virus production. The presence of ionomycin completely reversed the
      inhibition of virus production by cocaine. The antiviral effects of cocaine
      appear to be caused by modulation of intracellular calcium and, to a lesser
      extent, by the enhancement of interferon production.

PMID- 9142143
TI  - Distribution of elastin in hamsters and the turnover rates of different elastin
      pools.
AB  - Desmosine (DES) and isodesmosine (IDES) concentration in the urine can be used as
      a noninvasive method of assessing degradation of mature elastin in normal and
      pathologic states. The present study was undertaken to determine the distribution
      of elastin among organs and tissues of normal hamsters, and to determine the
      turnover rates of two elastin-containing organs (lung, thoracic aorta) as a
      reflection of their contributions to DES and IDES excretion in the urine.
      Hamsters were metabolically labeled at 5 days of age with 14C-lysine and studied
      at 1.5, 4.5, 8, and 12 months of age. The aorta DES + IDES-associated
      radioactivity did not change significantly over the age span of 1.5-12 months.
      Lung DES + IDES-associated radioactivity decreased with a half-life of 420 days.
      Measurement of DES + IDES pools in other tissues, with relatively low
      concentrations of elastin, was carried out by the isotope dilution technique. At
      12 months of age, the head and paws pool, skin, skeletal muscle, gastrointestinal
      tract, heart-liver-kidney-spleen pool, lungs, and thoracic aorta represented 37%,
      28%, 13%, 11%, 6%, 4%, and 1%, respectively, of total body DES + IDES. The organs
      with the highest DES + IDES-specific radioactivity at 12 months were heart-liver
      kidney-spleen, lung, and gastrointestinal tract, with 310, 217, and 217 dpm/nmol,
      respectively. Skin had the lowest specific radioactivity, with 90 dpm/nmol. The
      specific radioactivity of DES + IDES in urine was 62 dpm/nmol at 12 months, down
      from 251 dpm/nmol at 1.5 months. These data clearly indicate that non-lung
      tissues contain a high proportion of the total body DES + IDES and suggest that
      pathology in these other pools of DES + IDES could result in significant
      elevation of urinary DES + IDES. Nevertheless, the relatively high specific
      radioactivity of DES + IDES in lung elastin as compared with urine makes
      monitoring labeled urinary DES + IDES in this animal model a sensitive tool for
      assessing elastin degradation in experimental lung disease.

PMID- 9142144
TI  - Pelvic exenteration for locally advanced rectal carcinoma: factors predicting
      improved survival.
AB  - BACKGROUND: The purpose of this retrospective review was to determine whether a
      number of clinicopathologic factors (age, gender, type of exenteration, tumor
      extent, adjuvant therapy, tumor DNA ploidy, and S-phase fraction) that could be
      determined before operation were useful in predicting survival in patients
      undergoing pelvic exenteration for rectal cancer. METHODS: Between 1983 and 1992,
      40 patients (15 male and 25 female) at our institution underwent pelvic
      exenteration for rectal adenocarcinoma in which tumor-free pathologic margins
      were obtained. Twenty-nine patients presented with primary tumors; 11 had
      recurrent disease. A total exenteration was performed in 20 patients, posterior
      exenteration in 18 patients, and an anterior exenteration in 2 patients. RESULTS:
      By multivariate (Cox proportional hazards regression) analysis, age, preoperative
      chemoradiation therapy, and an S phase of 10% or greater were found to be
      significant predictors of survival. Age older than 55 years was associated with a
      relative risk for cancer-related death (RR) of 0.13 (p = 0.02), and
      chemoradiation had an RR of 0.05 (p = 0.01), indicating their beneficial effect.
      An S-phase fraction of 10% or greater had an RR of 16.97 (p = 0.03), indicating a
      poor survival. The clinicopathologic factors listed above were used to derive a
      prognostic index (PI). A PI of less than 1.37 was associated with a 5-year
      survival rate of 65% (low risk), whereas patients with a PI of 1.37 or greater
      had a 5-year survival rate of 20% (high risk) (p = 0.005). CONCLUSIONS: These
      results indicate that adjuvant chemoradiation may significantly improve survival
      in patients who require pelvic exenteration for resection of locally advanced
      rectal carcinoma. An S-phase fraction of 10% or greater is also predictive of a
      poor outcome. Use of these factors allowed the generation of a PI that identifies
      high- and low-risk patients. Consideration of the ability to deliver
      chemoradiation and the determinates of the tumor S-phase fraction in patients
      requiring pelvic exenteration for rectal cancer may be helpful in predicting
      outcome and planning therapy.

PMID- 9142145
TI  - Late development of bile duct cancer after sphincteroplasty: a ten- to twenty-two
      year follow-up study.
AB  - BACKGROUND: Transduodenal sphincteroplasty is designed to destroy the sphincteric
      muscle fibers, producing a terminal choledochoduodenostomy. In the absence of
      Oddi's sphincter, intestinal contents with both activated pancreatic juice and
      bacterial flora are refluxed into the bile duct and remain there for a prolonged
      time. The long-term effect of producing the reflux has not been evaluated to
      date. METHODS: One hundred nineteen consecutive patients undergoing transduodenal
      sphincteroplasty between February 1973 and July 1984 were included in this study.
      Postoperative clinical courses of 108 patients could be evaluated by means of a
      retrospective review of the hospital records. Median follow-up was 18 years.
      RESULTS: Eight cases (7.4%) of primary bile duct cancer were found among the 108
      cases at intervals of 1 to 20 years after sphincteroplasty. Two patients had
      concurrent hepatolithiasis. The patency of sphincteroplasty was confirmed in all
      cases, and the bile was infected in seven cases. Pathologic specimens obtained
      demonstrated cholangiocarcinomas and various degrees of atypical hyperplastic
      lesions under the background of chronic cholangitis. CONCLUSIONS: Chronic
      cholangitis can be an important causative factor in late development of bile duct
      cancer after sphincteroplasty. Any patients treated with choledochoduodenostomy
      should be closely monitored for late cholangiocarcinoma.

PMID- 9142146
TI  - Unexpected action of platelet activating factor antagonism after fluid
      resuscitation from traumatic shock.
AB  - BACKGROUND: We have shown that therapy directed at polymorphonuclear neutrophil
      (PMN) CD18 receptors attenuates sequelae associated with a post-trauma endotoxin
      (lipopolysaccharide [LPS]) challenge. Platelet activating factor (PAF) stimulates
      PMNs by CD18-independent pathways, and WEB-2086, a PAF receptor antagonist,
      blunts septic symptoms in many experimental models. This study tested the
      hypothesis that the blockade of non-CD18 dependent PMN adherence attenuates
      trauma- and LPS-evoked pulmonary dysfunction. METHODS: We performed three
      experiments. First, anesthetized swine were subjected to hind-limb trauma and 30%
      hemorrhage. After 1 hour animals were resuscitated with shed blood, lactated
      Ringer's solution (LRS), and WEB-2086 (10 mg/kg/hr) or vehicle. After a 72-hour
      recovery period, LPS was administered. LPS was then administered without an
      earlier episode of traumatic shock to animals treated with WEB-2086 or vehicle.
      Finally, PAF was infused before and after trauma and a dose response curve was
      obtained. RESULTS: Surprisingly, PAF blockade increased mortality after trauma (5
      of 11 WEB-2086 animals versus 1 of 9 vehicle animals; p = 0.15) and depressed
      cardiac index and O2 delivery at 72 hours (p < 0.05). After LPS administration
      WEB-2086 treated pigs were unable to manifest the hyperdynamic circulatory
      compensation seen in the vehicle pigs. In the absence of traumatic shock, WEB
      2086 was associated with reduced mortality (four of five WEB-2086 treated pigs
      versus two of five vehicle pigs survived 5 hours; p = 0.07) and improved arterial
      PO2 (p = 0.05) and base excess (p = 0.04) 60 minutes after LPS administration.
      The dose response curve for PAF infusion on the cardiac index was altered after
      trauma compared with the nontraumatized state. CONCLUSIONS: Because WEB-2086 had
      unexpected and fundamentally opposite properties before and after trauma, PAF may
      have a previously undescribed homeostatic role in the compensatory response to
      injury. These results also suggest that blockade of endogenous inflammatory
      mediators can have a positive or negative action, depending on the timing of
      administration and the preexisting condition.

PMID- 9142147
TI  - Total gastrectomy for primary gastric lymphoma at stages IE and IIE: a
      prospective study of fifty cases.
AB  - BACKGROUND: Treatment of primary gastric lymphoma at Ann Arbor stage IE or IIE is
      controversial. Randomized trials to compare various modalities are not feasible
      because of the rarity of this disease. We have prospectively treated patients by
      means of primary surgery to achieve complete local control and accurate staging.
      METHODS: Between 1987 and 1995, 50 patients with stage IE or IIE gastric lymphoma
      were prospectively treated by total gastrectomy with systematic lymphadenectomy.
      When nodal metastases were histologically confirmed or the resection was
      noncurative, chemotherapy was added. Intragastric tumor spread, lymph node
      metastasis, and treatment results were examined. RESULTS: Resection was
      potentially curative in 48 cases. There were no operative deaths. Histologically,
      the middle third of the stomach was most frequently involved. Either the proximal
      two thirds or the entire stomach was involved in 62% of all patients. Lymph node
      metastasis was demonstrated in 25 patients. The deeper the tumor invasion in the
      gastric wall, the more frequent and distant the nodal involvement. The 5-year
      survival rate was 85.6%, excluding one death caused by heart disease.
      CONCLUSIONS: Primary surgery followed by chemotherapy in selected cases is an
      appropriate strategy for primary gastric lymphoma in patients in whom this
      regimen can be safely carried out.

PMID- 9142148
TI  - Randomized trial of three types of gastrojejunostomy in unresectable
      periampullary cancer.
AB  - BACKGROUND: A gastrojejunostomy with duodenal partition was designed to clarify
      whether so-called circulus vomiting exists and, if so, its clinical significance,
      by comparing it with two other types of gastrojejunostomy commonly used for
      gastric bypass in unresectable periampullary cancer. METHODS: Forty-five patients
      with unresectable periampullary cancer complicated by gastric outlet obstruction
      (GOO) were recruited into this study between May 1992 and November 1995. They
      were randomized to receive one of the three types of gastrojejunostomy. The
      anastomosis in type I gastrojejunostomy was performed at the jejunum 20 cm distal
      to the ligament of Treitz. Type II was similar to type I except that in type II a
      duodenum partition was done by linear stapler 1 cm beyond the pylorus. Type III
      gastrojejunostomy was performed at the Roux-limb jejunum 60 cm distal to
      biliojejunostomy. RESULTS: "Food reentry" was noted in three (21%) of the type I
      patients, as determined by upper gastrointestinal (UGI) study. Of the three, one
      patient had severe circulus vomiting, one had anorexia, and one had no major
      symptoms. When patients were evaluated immediately after oral diet intake
      resumed, the incidence (27%) of clinical GOO symptoms and mean value of gastric
      emptying time (GET1/2, 118.1 +/- 39.2 min) were significantly lower in type II
      patients than in types I and III patients. When evaluated I month after
      operation, the incidence (7% and 17%, respectively) of clinical symptoms of GOO
      and mean value of GET1/2 (42.0 +/- 23.0 and 35.6 +/- 5.4 min, respectively) were
      significantly lower in both type II and type III patients than in type I
      patients. The type II patients resumed oral diet after operation 3.5 days earlier
      than type I patients, p < 0.05. CONCLUSIONS: Circulus vomiting induced by food
      reentry does exist if the gastrojejunostomy is performed as the type I
      gastrojejunostomy in this study. The newly designed type II gastrojejunostomy
      with duodenal partition is an easy, safe, and effective gastric bypass and avoids
      the problem of food reentry.

PMID- 9142149
TI  - Diabetes-impaired healing and reduced wound nitric oxide synthesis: a possible
      pathophysiologic correlation.
AB  - BACKGROUND: Nitric oxide (NO) is synthesized in wounds, but its role in the
      healing process is not fully understood. The inhibition of NO production during
      wound healing is accompanied by decreased wound reparative collagen deposition.
      To further define the role of NO in reparative collagen accumulation, we studied
      its production during diabetes-induced wound healing impairment. METHODS: Male
      Sprague-Dawley rats (290 to 310 gm) were rendered diabetic by intraperitoneal
      streptozotocin administration. Seven days after induction of diabetes (blood
      glucose greater than 300 mg/dl), the rats underwent dorsal skin incision and
      subcutaneous implantation of polyvinyl alcohol sponges. Beginning on the day of
      wounding, 21 diabetic animals were treated with 3 units/day insulin via
      intraperitoneally implanted miniosmotic pumps. Ten days after injury, wound
      breaking strength was determined, and wound collagen accumulation and types I and
      III collagen gene expression were measured in subcutaneously implanted polyvinyl
      alcohol sponges. NO-synthesis, as measured by nitrite/nitrate accumulation, was
      determined in wound fluid and in supernatants of wound cell cultures. RESULTS:
      Streptozotocin-induced diabetes markedly impaired wound breaking strength and
      collagen deposition. A parallel decrease occurred in wound NO synthesis as
      reflected by decreased nitrite/nitrate concentration in wound fluid and in
      diminished ex vivo NO production by wound cells. Insulin treatment partially but
      significantly improved wound mechanical strength (p < 0.01) and collagen
      accumulation (p < 0.001). Decreased wound NO accumulation and ex vivo NO
      production by wound cells were also partially restored by insulin treatment.
      CONCLUSIONS: Impaired diabetic wound healing is paralleled by decreased wound NO
      synthesis, supporting the hypothesis that NO plays a significant role in wound
      reparative collagen accumulation.

PMID- 9142150
TI  - Effect of pentoxifylline on hepatic ischemia and reperfusion injury.
AB  - BACKGROUND: Although pentoxifylline has been shown to improve tissue oxygenation
      and restore hepatocellular function after hemorrhagic shock, its effect on
      hepatic ischemia and reperfusion injury has not been fully clarified. The purpose
      of this study was to determine whether pentoxifylline exerted beneficial effects
      on liver histopathologic changes and enzymatic release caused by ischemia and
      reperfusion. METHODS: Warm, reversible hepatic ischemia/reperfusion injury was
      induced in four groups of pigs. Preoperative oral (24 mg/kg or 50 mg/kg) or
      intraoperative intravenous (50 mg/kg) pentoxifylline was administered. Control
      animals received intravenous normal saline solution. RESULTS: Untreated control
      animals exhibited significant liver damage expressed by hepatic histopathologic
      changes and high plasma levels of aminotransferases. Decreased animal survival
      was seen in the untreated group. All treated animals survived. Pentoxifylline
      given orally did not improve histopathologic changes or enzyme release.
      Intravenous administration caused significant amelioration of liver tissue
      damage, marked reduction of aspartate aminotransferase levels, and mild
      attenuation of alanine aminotransferase levels, as compared with control.
      CONCLUSIONS: This study indicates that intraoperative, intravenous pentoxifylline
      reduces hepatic injury after warm ischemia and reperfusion.

PMID- 9142151
TI  - Is reperfusion injury an important cause of mucosal damage after porcine
      intestinal ischemia?
AB  - BACKGROUND: Intestinal ischemic injury is exacerbated by reperfusion in rodent
      and feline models because of xanthine oxidase-initiated reactive oxygen
      metabolite formation and neutrophil infiltration. Studies were conducted to
      determine the relevance of reperfusion injury in the juvenile pig, whose low
      levels of xanthine oxidase are similar to those of the human being. METHODS:
      Ischemia was induced by means of complete mesenteric arterial occlusion,
      volvulus, or hemorrhagic shock. Injury was assessed by means of histologic
      examination and measurement of lipid peroxidation. In addition, myeloperoxidase,
      as a marker of neutrophil infiltration, and xanthine oxidase-xanthine
      dehydrogenase were measured. RESULTS: Significant ischemic injury was evident
      after 0.5 to 3 hours of complete mesenteric occlusion or 2 hours of shock or
      volvulus. In none of these models was the ischemic injury worsened by
      reperfusion. To maximize superoxide production, pigs were ventilated on 100% O2,
      but only limited reperfusion injury (1.2-fold increase in histologic grade) was
      noted. Xanthine oxidase-xanthine dehydrogenase levels were negligible (0.4 +/-
      0.4 mU/gm). CONCLUSIONS: Reperfusion injury may not play an important role in
      intestinal injury under conditions of complete mesenteric ischemia and low-flow
      states in the pig. This may result from low xanthine oxidase-xanthine
      dehydrogenase levels, which are similar to those found in the human being.

PMID- 9142152
TI  - Efficacy of preoperative diagnostic imaging localization of technetium 99m
      sestamibi scintigraphy in hyperparathyroidism.
AB  - BACKGROUND: Until now, preoperative parathyroid imaging has been considered
      unnecessary because currently available techniques do not provide any better
      results than an expert surgeon. We conducted a multicenter prospective study
      evaluating the capability of technetium 99m sestamibi scintigraphy in the
      preoperative identification of pathologic glands. METHODS: Ninety-three patients
      with hyperparathyroidism, seven of them reoperative cases, were studied. In
      addition, 20 age-matched normocalcemic control subjects were also studied.
      RESULTS: Surgical confirmation of scintigraphic images was obtained in 91 of 93
      cases (sensitivity, 97.8%). In all reoperative cases (n = 7), in all cases of
      ectopic glands (whether operated or not; n = 6), and in all patients with a
      single-gland disease (n = 70), topographic identification of the pathologic gland
      was correct in 100%. In multiple-gland disease (n = 23), involvement of more than
      one gland was visualized in only 61% of the patients; however, in 91% of
      patients, at least one gland was localized. Surgical success-defined as
      postoperative normocalcemia-with this approach was 100%. All scans of
      normocalcemic control subjects were negative. Of 31 patients in whom a
      multinodular goiter coexisted, seven presented a significant radionuclide
      background at 120 minutes' scan. False-positive images were found together with
      those corresponding to the pathologic glands in only three cases. CONCLUSIONS:
      99mTc-sestamibi is a highly reliable, sensitive, and specific technique for
      imaging of pathologic glands in hyperparathyroidism, especially in single-gland
      disease. It may be considered as a first line single-procedure when a
      preoperative topographic diagnosis is required.

PMID- 9142153
TI  - Effect of glutamine-enriched total parenteral nutrition on small intestinal gut
      associated lymphoid tissue and upper respiratory tract immunity.
AB  - BACKGROUND: Our prior work shows that total parenteral nutrition (TPN) causes
      small intestinal gut-associated lymphoid tissue (GALT) atrophy, lowers small
      intestinal immunoglobulin A (IgA) levels, and impairs secretory IgA-mediated
      mucosal immunity of the upper respiratory tract. These experiments examine
      whether an isonitrogenous 2% glutamine-enriched TPN solution prevents these
      changes. METHODS: Institute of Cancer Research mice were randomized to chow
      (chow), intravenous feeding of a TPN solution (TPN), or glutamine-enriched TPN
      (glutamine) groups. After mice were fed for 5 days, lymphocytes were isolated
      from Peyer's patches, the intraepithelial layer, and lamina propria to determine
      cell yields and phenotypes. Total small intestinal IgA levels were analyzed by
      means of enzyme-linked immunosorbent assay. In a second series of experiments,
      mice underwent intranasal inoculation with H1N1 virus to establish immunity.
      After 3 weeks mice were randomized to chow, TPN, or glutamine groups. After
      feeding for 5 days, mice were rechallenged with intranasal virus and killed at 40
      hours to determine viral shedding from the upper respiratory tract. RESULTS:
      Total lymphocyte yield in the Peyer's patches, the intraepithelial layer, and
      lamina propria, small intestinal IgA levels, and the CD4+/CD8+ ratio in the
      lamina propria decreased with TPN but remained normal with glutamine. On
      rechallenge, 87% of the mice in the TPN group shed virus in nasal secretions,
      whereas only 38% of the glutamine-treated group (p < 0.05 versus TPN) and 7.1% of
      the chow group (p < 0.002 versus TPN) were virus positive. CONCLUSIONS:
      Isonitrogenous supplementation of TPN with 2% glutamine improves IgA-mediated
      protection in the upper respiratory tract and normalizes GALT populations.

PMID- 9142154
TI  - Laparoscopic colectomy shortens postoperative ileus in a canine model.
AB  - BACKGROUND: Proponents of laparoscopic colectomy claim a more rapid return of
      gastrointestinal function, but objective data supporting this contention are
      lacking. Our aim was to compare the duration of delay in gastrointestinal transit
      after total laparoscopic, laparoscopic-assisted, and open colonic resection.
      METHODS: Thirty-nine female dogs were assigned to three groups: group 1,
      laparoscopic colectomy; group 2, laparoscopic-assisted colectomy; and group 3,
      open colectomy. Transit studies were performed before operation and on days 1, 2,
      3, and 5 after a mid-descending colectomy with end-to-end anastomosis. Gastric
      emptying of liquids and small bowel transit of liquids were determined by means
      of radionuclide techniques. Gastric emptying of solids and colonic transit were
      measured by following transit of radiopaque spheres instilled into the stomach
      and proximal colon, respectively. RESULTS: With each dog as its own control,
      gastric emptying returned to preoperative values by 2 days in group 1, 3 days in
      group 2, and 5 days in group 3. Small bowel transit returned to preoperative
      values on day 3 for groups 1 and 2 and on day 5 for group 3. Gastric emptying of
      solids and colonic transit returned to preoperative values on day 3 for group 1
      and on day 5 for groups 2 and 3. CONCLUSIONS: These observations show that
      laparoscopic resection techniques in this canine model resulted in a more rapid
      return to normal gastrointestinal transit compared with open colectomy.

PMID- 9142155
TI  - Innominate artery occlusive disease: management with central reconstructive
      techniques.
AB  - BACKGROUND: The purpose of this study was to review our experience with central
      vascular reconstruction for innominate artery occlusive disease. Eighteen
      patients underwent central reconstruction for innominate artery (IA) occlusive
      disease during an 8-year period (1986 to 1994). Mean age was 59 years (range, 36
      to 77 years). Women outnumbered men 12 to 6. All patients had symptoms including
      amaurosis fugax 55%, transient ischemic attacks 44%, vertebrobasilar
      insufficiency 44%, and arm claudication 33%. The IA was occluded in three
      patients and stenotic in 15. Three patients underwent previous extrathoracic
      bypass procedures for IA lesions that failed. METHODS: Operations performed
      through a median sternotomy included aortocarotid bypass with reimplantation of
      the subclavian (n = 10) and aortoinnominate bypass (n = 7). Transection and
      oversewing of the IA was performed in all but one patient, in whom ligation of
      the IA was performed. One patient with severe chronic obstructive pulmonary
      disease and previous coronary artery bypass grafting underwent retrograde
      transluminal IA angioplasty with endovascular stent placement via a carotid
      approach. Four patients underwent concomitant carotid endarterectomy). Two
      patients underwent concomitant coronary artery bypass grafting at the time of IA
      reconstruction. RESULTS: There was one operative death from myocardial
      infarction. Perioperative morbidity included dysrrhythmia (three), respiratory
      insufficiency (three), subendocardial myocardial infarction (two),
      cerebrovascular accident with complete recovery (two), hemorrhage (one), and
      acute graft occlusion (one). All grafts remained patient at a mean follow-up of
      21 months (range, 8 to 60 months). The only patient who underwent ligation of the
      IA required a subsequent revision of the IA to transection and oversewing for an
      embolic event at 4 months status-post aortocarotid bypass. The patient who
      underwent angioplasty remained asymptomatic with a patient IA at 12 months.
      Average length of stay for transthoracic repair was 14 days and for transluminal
      angioplasty 2 days. CONCLUSIONS: Innominate artery bypass based on the ascending
      aorta is effective in providing relief of symptoms and has a high patency rate.
      Because of the significant morbidity, these procedures should be reserved for
      patients with symptoms. The IA should be transected and oversewn to prevent
      recurrent embolism. Transcarotid, retrograde angioplasty provides an alternative
      approach to stenotic lesions located in the IA or proximal common carotid artery.
      An aggressive approach directed at defining coronary artery disease is an
      invaluable adjunct to the proper treatment of this patient population.

PMID- 9142157
TI  - Functional perineal colostomy with pudendal nerve anastomosis following anorectal
      resection: a cadaver operation study on a new procedure.
AB  - BACKGROUND: We have previously studied functional perineal colostomy that used
      skeletal muscle with pudendal nerve anastomosis (PNA) following anorectal
      resection in an animal model. In that study the neosphincter reconstructed with
      PNA achieved the proper functions of the external anal sphincter resulting in a
      satisfactory defecatory condition. This study was a preliminary step before
      applying this procedure to human beings. METHODS: We reconstructed a new anal
      sphincter by using the lower part of the gluteus maximus muscle (lower GMM) with
      PNA in a total of six sides of four human cadavers and investigated the anatomic
      problems associated with this procedure. RESULTS: We classified the branching
      patterns of the inferior gluteal nerve into three types. The length of the
      branches of the inferior gluteal nerve to the lower GMM varied from 32 to 76 mm
      (median, 57 mm). The length of the pudendal nerve (PN) passing out below the
      sacrotuberous ligament varied from 21 to 44 mm (median, 29.5 mm). The PN was
      anastomosed to the nerve innervating the lower GMM with the redundancy of 17 to
      36 mm (median, 24.5 mm). In all cases the anal sphincter reconstruction with a
      PNA maneuver was anatomically feasible by using the lower GMM. The length of the
      new anal canal was 65 to 80 mm (median, 67.5 mm). CONCLUSIONS: The PNA maneuver
      was an anatomically applicable method to make a neoanus in human beings.
      Preparation for the application of this method to human beings was accomplished.

PMID- 9142156
TI  - Impact of cytomegalovirus serology on graft survival in living related kidney
      transplantation: implications for donor selection.
AB  - BACKGROUND: The impact of cytomegalovirus in living related kidney
      transplantation remains controversial. This study considers the implications of
      donor and recipient cytomegalovirus (CMV) serology for the selection of living
      related donor. METHODS: Graft survival was estimated by using the bivariate
      Kaplan-Meier method and multivariate Cox proportional hazards analysis for 7659
      living related first transplantations performed in the United States between 1989
      and 1994. The effects of donor CMV serology were estimated with respect to
      recipient CMV serology and compared with human leukocyte antigen (HLA) matching,
      transplantation, donor, and recipient characteristics. The implications of these
      estimates for the selection of living related donors were considered. RESULTS:
      From Kaplan-Meier estimates, donor CMV-seropositive kidneys were associated with
      significantly reduced graft survival for CMV-seronegative recipients (p = 0.0002)
      but not CMV-seropositive recipients (p = 0.1623). These findings were verified by
      use of Cox proportional hazards analysis accounting for covariate factors. The
      impact of donor CMV-seropositive kidneys on CMV-seronegative recipients was
      similar to one HLA-DR match, greater than one HLA-B match, and significantly
      greater than one HLA-A match (p = 0.0331). CONCLUSIONS: Results identify donor
      CMV serology as an important determinant of transplantation outcome for living
      related first kidney transplant recipients who are themselves CMV seronegative.
      Consideration should be given to donor and recipient CMV serology when selecting
      an appropriate donor for living related kidney transplantation.

PMID- 9142158
TI  - An old Yankee surgeon entertains a new idea.

PMID- 9142159
TI  - Modulation of a cardiogenic shock inducible RNA by chemical stress:
      adapt73/PigHep3.
AB  - BACKGROUND: Understanding how mammalian cells respond to stress is important in
      the study, detection, and therapy of stress-related disorders. We have been
      studying cellular stress response in hamster HA-1 cells by using an adaptive
      response model. HA-1 cells respond to a minimally toxic "pretreatment" dose of
      hydrogen peroxide by synthesizing RNAs and proteins that protect them against
      subsequent exposure to a higher cytotoxic concentration of peroxide. The purpose
      of our studies is to identify and partially characterize any mRNA whose steady
      state level is significantly modulated during adaptation. METHODS: HA-1 cells
      were exposed to a pretreatment dose of hydrogen peroxide and RNA extracted. The
      differential display technique was used to identify modulated mRNAs. The effects
      of calcium ionophore A23187 and cis (II)-platinum on the modulation of mRNA from
      HA-1 cells and A23187 on the modulation of mRNAs from human IMR-90 cells were
      also determined. RESULTS: One of the RNAs induced by a pretreatment concentration
      of hydrogen peroxide was designated adapt73. The size of the induced adapt73 RNA
      was determined to be 2.1 kb. Induction of adapt73 was maximal 5 hours after
      peroxide treatment, but elevated levels were still obvious at 10 hours. This
      induction was not specific to oxidative stress, because other stress agents
      including as (II)-platinum and especially calcium ionophore A23187 also induced
      adapt73 mRNA levels. Partial sequencing of adapt73 and a subsequent GenBank
      homology search revealed extensive homology to a novel RNA from pig, designated
      PigHep3, that was identified as a cardiogenic shock response gene from liver in
      pigs that were undergoing resuscitation after circulatory shock. Homology to a
      completely sequenced but uncharacterized human homolog was also found. Using a
      partially sequenced expressed sequence tag (EST) human clone to adapt73, we
      probed Northern blots containing RNA from IMR-90 human fibroblasts treated with
      A23187. A strongly induced human adapt73 mRNA homolog was observed, almost
      identical in size to its hamster homolog. In vitro transcription and translation
      of the human EST clone revealed a translatable Adapt73 protein product.
      CONCLUSIONS: These data indicate that adapt73/PigHep3 RNA can be induced by
      multiple chemical stress, that these inductions occur under protective or
      adaptive response conditions, that there is an inducible human homolog to
      adapt73, and suggest that adapt73 may be an important physiologic mediator of
      organ and cellular shock response in mammals.

PMID- 9142160
TI  - Superior mesenteric artery occlusion and peripheral emboli caused by an aortic
      ulcer in a young patient with antiphospholipid syndrome.

PMID- 9142161
TI  - Unbalanced cross circulation in conjoined twins.

PMID- 9142162
TI  - Acute suppurative thyroiditis and necrosis of the thyroid gland: a rare endocrine
      manifestation of acquired immunodeficiency syndrome.

PMID- 9142163
TI  - Enteric duplication presenting as cystic tumors of the pancreas.

PMID- 9142164
TI  - Sources of variability in mutant frequency determinations in different organs of
      lacZ plasmid-based transgenic mice: experimental features and statistical
      analysis.
AB  - Sources of variability that may affect the measurement of mutant frequencies in
      lacZ plasmid-based transgenic mice, including rescue-to-rescue, animal-to-animal
      (within organ), and organ-to-organ, were studied in the context of some of the
      experimental features that distinguish this model from other currently used
      systems. Statistical analysis of repeated determinations of DNA from kidney,
      spleen, liver, lung, and brain indicated that 350,000 colony-forming units from
      each of three animals should be analyzed per treatment group in order to detect a
      50% difference in mutant frequencies. Consideration is given to some of the
      experimental features of the transgenic assay system, including its positive
      selection system, its rescue efficiency, the ability to detect large deletions in
      the lacZ target genes, the contribution of Escherichia coli-derived mutations to
      the spontaneous mutant frequencies observed in vivo, and cost effectiveness of
      mutant frequency determinations.

PMID- 9142166
TI  - Absence of systemic in vivo genotoxicity after dermal exposure to ethyl acrylate
      and tripropylene glycol diacrylate in Tg.AC (v-Ha-ras) mice.
AB  - Acrylates may be polymerized to stable surface coatings (paints, lacquers, inks,
      etc.) by alkylation via the Michaelis-type addition reaction. Thus, acrylates
      have an inherent potential as electrophiles to be genotoxic, limited in their
      biological activity by their physicochemical properties. To evaluate their
      systemic genotoxicity, ethyl acrylate (EA), tripropylene glycol diacrylate
      (TPGDA), or Lacquer A, an ultraviolet radiation curable lacquer containing TPGDA
      as the active ingredient, were applied dermally to Tg.AC mice (3 times a week for
      20 weeks). Peripheral blood leukocytes were evaluated for DNA damage (single
      strand breaks, alkali labile sites, DNA crosslinking) at weeks 4, 8, 12, 16, and
      20 by using the alkaline (pH: 13) single cell gel (SCG) assay. Peripheral blood
      polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) were
      evaluated for the presence of micronuclei at week 20. The extent of DNA migration
      in leukocytes and the frequency of micronucleated erythrocytes was not
      significantly altered by treatment with TPGDA when administered alone or in
      Lacquer A or with EA, at doses that induced cell proliferation in keratinocytes.
      The absence of genotoxicity in these two cell populations suggests that these
      acrylates are not genotoxic or that they are not absorbed systemically when
      applied dermally. However, a significant, dose-dependent increase in the
      percentage of PCE relative to the vehicle control was present in mice treated
      with TPGDA, while a dose-dependent, but nonsignificant, increase in the
      percentage of PCE was observed in mice treated with Lacquer A. This observed
      increase in the rate of erythropoiesis may reflect bone marrow/blood toxicity, a
      homeostatic mechanism in response to the treatment-induced tumor burden, and/or a
      hematopoietic response to epidermal keratinocyte cytokines induced by tissue
      injury.

PMID- 9142165
TI  - Germ cell mutagenicity of three metabolites of 1,3-butadiene in the rat:
      induction of spermatid micronuclei by butadiene mono-, di-, and diolepoxides in
      vivo.
AB  - Three metabolites of the industrial chemical 1,3-butadiene (BD), namely butadiene
      monoepoxide (BMO, 3,4-epoxy-1-butene), diepoxide (DEB, 1,2;3,4-diepoxybutane),
      and diolepoxide (DE, 3,4- epoxybutane-1,2-diol) were studied for germ cell
      mutagenicity using the rat spermatid micronucleus (MN) test. All three epoxides
      increased slightly, but significantly, the frequency of spermatid MN. The most
      sensitive stage to the action of BMO and DEB was preleptotene (meiotic S phase)
      harvested at 18-day time intervals after treatment. The dose-response for BMO
      followed a second order curve at this time interval, with maximum MN induction at
      the dose of 186 mumol/kg and lower induction of higher doses. Late stages of the
      meiotic prophase (late pachytene-diplotene-diakinesis) also showed some
      sensitivity to the three epoxides. Stem cell spermatogonia were affected by DEB
      as observed by a slight induction of spermatid micronuclei 50 days after
      treatment. No clear cytotoxic effects were observed by measuring testicular
      weight or cell numbers of seminiferous epithelial stage 1 18 days after the
      treatments. DEB at the dose 387 mumol/kg caused a slight inhibition of
      spermatogonial DNA synthesis in stage I and a delay of meiotic DNA replication
      observed in stage XII 72 hr after treatment. Since BMO is able to induce
      spermatid MN in the rat, the present results, together with previous data,
      indicate that rat bone marrow MN results that are negative for both BD and BMO
      cannot directly predict mutagenicity in male germ cells. The results also
      emphasize that tissue; species, and strain-specific differences in metabolism
      have to be taken into account when the genetic risks of human butadiene exposure
      are evaluated. The results support the conclusion that 1,3-butadiene is a germ
      cell mutagen-possibly also in humans.

PMID- 9142167
TI  - Aphidicolin-sensitive specific common fragile sites: a biomarker of exposure to
      pesticides.
AB  - In this work, we analyzed the aphidicolin-sensitive common fragile sites in seven
      females and four males occupationally exposed to pesticides and in ten controls.
      The same males had been monitored one year earlier in a previous study by the
      same authors. Results showed enhanced expression in exposed subjects at eight
      bands, namely, 6q25, 7p22, 7q22, 7q32, 13q14, 14q24, 16q22, and 16q23. Most of
      these bonds were fragile sites and breakpoints involved in chromosome
      rearrangements found in hematopoietic tumors. Moreover, six of these bands were
      already detected, with enhanced expression, in the first monitoring carried out
      on male subjects. These results indicated that fragile sites analysis is a
      reproducible cell response to human exposure to pesticides.

PMID- 9142168
TI  - DNA damage and cytotoxicity induced in mammalian cells by a
      tetramethylfuroquinolinone derivative.
AB  - 1,4,6,8-Tetramethyl-2H-furo[2,3-h]quinolin-2-one [FQ] is an angelicin isoster
      characterized by a strong photosensitizing activity FQ shows a significant
      antiproliferative activity also in the dark, i.e., without UVA activation. The
      cytotoxic activity of FQ in the dark was detected in HeLa cells and in normal
      human lymphocytes; FQ showed notable antiproliferative effects, barely lower in
      comparison with ellipticine, used as a reference Similar results were obtained
      studying the FQ's capacity for forming chromosome aberrations. For both FQ and
      ellipticine, the chromosomal damage correlated closely with cell killing, when
      compared with ellipticine at the same levels of survival, FQ appeared to be much
      less genotoxic. Using alkaline elution we have investigated the ability of FQ to
      damage DNA. The formation of equivalent amounts of single-strand breaks (SSB) and
      DNA-protein cross-links (DPC) was observed; in addition, these lesions appeared
      to be located at the same sites in DNA. Experiments carried out with neutral
      elution demonstrated the formation of double-strand breaks (DSB). All these data
      are consistent with an inhibition of topoisomerase II; this hypothesis was
      confirmed performing an enzymatic test in vitro using topoisomerase II from
      Drosophila melanogaster embryos.

PMID- 9142169
TI  - Lack of effect of long-term fluoride ingestion on blood chemistry and frequency
      of sister chromatid exchange in human lymphocytes.
AB  - Two studies were conducted to assess the potential for adverse physiologic and
      genotoxic effects of long-term fluoride ingestion in adults residing in three
      communities with varying water fluoride levels (0.2 ppm, 1.0 ppm, and 4.0 ppm).
      All were long-time (> or = 30 years) residents of their respective communities.
      Plasma and urine samples were collected for fluoride analyses. Additional plasma
      was collected to determine blood chemistry, and plasma lymphocytes were examined
      to determine the frequency of sister chromatid exchange. Significant differences
      in urine (P = 0.001) and plasma (P = 0.0001) fluoride levels were found in the
      three communities. Seven of the blood parameters were statistically different
      among the communities, although all were within the defined normal range of the
      pathology laboratory. Sister chromatid exchange frequency was statistically
      higher in the 4.0 ppm fluoride community as compared to the other communities.
      Because of the higher SCE frequency in the 4.0 ppm fluoride community, a second
      study was performed to determine if the increased frequency was potentially
      related to the fluoride level of the communal water supply. Of the 58 adults
      recruited; 30 had used city water and 28 had used well water (< or = 0.3 ppm
      fluoride) as their principal water source for 30 years. Data analyses showed that
      the sister chromatid exchange frequency did not differ between the groups,
      indicating that the increased sister chromatid exchange frequency was not related
      to the fluoride level of the communal water. The investigation provided evidence
      that the long-term ingestion of water containing 4.0 ppm fluoride did not have
      any clinically important physiologic or genotoxic effects in healthy adults.

PMID- 9142170
TI  - Genotoxicity of humic acid in cultured human lymphocytes and its interaction with
      the herbicides alachlor and maleic hydrazide.
AB  - The genotoxicity of humic acid and its possible interaction with the herbicides
      alachlor and maleic hydrazide have been evaluated in cultured human lymphocytes
      from two donors. Humic acid and the two herbicides have been tested (alone and
      combined) for sister-chromatid exchange (SCE) induction. In addition, the effect
      of two different preincubation times, 2 and 24 hr, was analyzed. The results
      indicate that humic acid and the herbicides alachlor and maleic hydrazide appear
      to significantly enhance the frequency of SCE, the effect of the herbicides being
      more pronounced. With reference to the possible interaction of humic acid with
      the herbicides, the results do not show a common pattern, although mainly an
      additive effect was obtained. Nevertheless, there is some evidence suggesting
      that antagonism may occur, especially in the combined treatment of humic acid and
      maleic hydrazide.

PMID- 9142171
TI  - Genotoxicity of select herbicides in Rana catesbeiana tadpoles using the alkaline
      single-cell gel DNA electrophoresis (comet) assay.
AB  - Pesticides are broadly used for pest control in agriculture despite possible
      negative impacts they may pose to the environment. Thus, we examined the DNA
      damage caused by five herbicides commonly used in southern Ontario (Canada).
      Erythrocytes from Rana catesbeiana (bullfrog) tadpoles were evaluated for DNA
      damage following exposure to selected herbicides, using the alkaline single-cell
      gel DNA electrophoresis (SCG) or "comet" assay [Singh et al. (1988): Exp Cell Res
      175:184-191; Ralph et al. (1996): Eviron Mol Mutagen 28:112-120]. This approach
      involves detection, under alkaline conditions, of DNA fragments that upon
      electrophoresis migrate from the nuclear care, resulting in a comet formation.
      The herbicides tested, along with their active ingredients, were AAtrex Nine-O
      (atrazine), Dual-960E (metalochlor), Roundup (glyphosate), Sencor-500F
      (metribuzin), and Amsol (2,4-D amine). Tadpoles were exposed in the laboratory
      for a 24-hr period to several concentrations of the herbicides dissolved in
      dechlorinated water. Methyl methanesulphonate was used as a positive control. The
      herbicides AAtrex Nine-O-, Dual-960E-, Roundup-, and Sencor-500F-treated tadpoles
      showed significant DNA damage when compared with unexposed control animals,
      whereas, Amsol-treated tadpoles did not. Unlike the other responding herbicides,
      Sencor-500F did not show a relationship between dosage and DNA damage. In
      summary, the results indicate that at least some of the herbicides currently used
      in southern Ontario are capable of inducing DNA damage in tadpoles.

PMID- 9142172
TI  - No radioadaptive response to micronucleated polychromatic erythrocyte (MN-PCE)
      induction in murine peripheral blood in vivo.
AB  - The effect of conditioning pretreatment with 0.025 Gy of gamma rays on
      micronucleated polychromatic erythrocyte (MN-PCE) induction by 1.0 or 0.1 Gy of
      gamma rays was determined in murine peripheral blood. The adaptive and challenge
      doses as well as the timing of their administration were taken from a previously
      reported experiment [Farooqi and Kesavan (1992). Mutat Res 302:83-89]. The
      response was determined by the strategy of measuring the area below the curve
      (ABC) of MN-PCE induction vs. time. This strategy permits one to determine an
      index of total damage and to establish if conditioning exposure affects the
      timing of MN-PCE appearance in the blood stream, which in turn could cause an
      apparent difference in response between the conditioned and the unconditioned
      groups at specific times. The results indicate that low dose gamma ray
      pretreatment does not protect against MN-PCE induction by the challenge gamma ray
      dose, and that there was no change on the kinetics of MN-PCE appearance in
      peripheral blood.

PMID- 9142173
TI  - Enhancement of the clastogenicity of N-nitrosodialkylamines plus near-ultraviolet
      irradiation by ethanol in Chinese hamster lung fibroblasts.
AB  - Early work from our laboratory showed a synergistic action of N
      nitrosodialkylamines and near-ultraviolet light (UVA, 320-400 nm) to cause
      mutations in bacteria and phages. Recently we reported that N
      nitrosodialkylamines + UVA induces chromosome aberrations in Chinese hamster lung
      cells in culture. We have now found that ethanol can potentiate this clastogenic
      action of N-nitrosodialkylamines + UVA. When the cells were treated with N
      nitrosopyrrolidine (NPYR) or N-nitrosodiethylamine (NDEA) + UVA for 2 hours in
      the presence of 1% ethanol, approximately 2-fold increase in the numbers of cells
      with aberrant chromosomes was observed, compared to those found without the
      ethanol. NPYR/NDEA only ethanol only, or ethanol + UVA did not cause the
      aberrations. The enhancement was dependent on the concentration of ethanol.
      Treatment of cells with ethanol before the NPYR + UVA was ineffective. By
      contrast, treatment of cells with NPYR-UVA and then with ethanol was as effective
      as with the simultaneous treatment. Methanol showed synergistic effects similar
      to those of ethanol, but mannitol did not. Intracellular hydrogen peroxide was
      found to be increased twofold over that in the background by a treatment with
      ethanol + UVA. The alcohol-mediated enhancement of the clastogenic action of N
      nitrosodialkylamines + UVA may be a consequence of an increase in intracellular
      oxidative stress, or simply due to increased membrane permeability.

PMID- 9142174
TI  - Comparative study of DNA adduct formation in mice following inhalation of smoke
      from cigarettes that burn or primarily heat tobacco.
AB  - The genotoxic potential of mainstream smoke from a test cigarette (TOB-HT) that
      primarily heats tobacco and a representative tobacco-burning cigarette (Kentucky
      reference 1R4F) was compared in male B6C3/F1 mice after nose-only inhalation
      exposure. Mice were exposed 1 hr per day, 5 days/ week for a 4 week period to
      mainstream smoke at concentrations of 0, 0.16, 0.32, and 0.64 mg total
      particulate matter/liter of air. Micronuclei formation in bone marrow and
      peripheral blood polychromatic erythrocytes (PCE) of animals exposed to either
      the TOB-HT or 1R4F cigarette was not significantly different compared with
      control animals exposed nose-only to filtered and humidified air (sham controls).
      DNA adduct measurement by the 32P-post-labeling method indicated an exposure
      dependent increase in lung adducts of animals exposed to 1R4F cigarette smoke at
      all three concentrations with the mid and high exposure groups exhibiting
      statistically significant increases (P < 0.05) in adduct formation compared to
      sham-exposed animals. The concentration of DNA adducts in the lungs of animals
      exposed to the TOB-HT cigarette was not significantly increased (P < 0.05) at any
      concentration compared to sham-exposed controls. A statistically significant (P <
      0.05) concentration-dependent formation of DNA adducts was also observed in the
      heart tissues of animals exposed to smoke from the 1R4F cigarette at all three
      concentrations, but no significant increase in adduct formation was observed in
      heart DNA of the animals exposed to the TOB-HT cigarette (P < 0.05). Under the
      conditions of this experiment, the mainstream smoke from the TOB-HT cigarette was
      demonstrated to be less genotoxic in mice than mainstream smoke from the 1R4F
      cigarette, which is representative of cigarettes in the current U.S. market.

PMID- 9142175
TI  - Predicting rodent carcinogenicity from mutagenic potency measured in the Ames
      Salmonella assay.
AB  - Many in vitro tests have been developed to identify chemicals that can damage
      cellular DNA or cause mutations, and secondarily to identify potential
      carcinogens. The test receiving by far the most use and attention has been the
      Salmonella (SAL) mutagenesis test developed by Ames and colleagues [(1973): Proc
      Natl Acad Sci USA 70:2281-2285; (1975): Mutat Res 31:347-364], because of its
      initial promise of high qualitative (YES/NO) predictivity for cancer in rodents
      and, by extension, in humans. In addition to the initial reports of high
      qualitative predictivity, there was also an early report by Meselson and Russell
      [in Hiatt HH et al (1977): "Origins of Human Cancer, Book C: Human Risk
      Assessment," pp 1473-1481] of a quantitative relationship between mutagenic
      potency measured in SAL and carcinogenic potency measured in rodents, for a small
      number of chemicals. However, other reports using larger numbers of chemicals
      have found only very weak correlations. The primary purpose of this study was to
      determine whether mutagenic potency, as measured in a number of different ways,
      could be used to improve predictivity of carcinogenicity, either qualitatively or
      quantitatively. To this end, eight measures of SAL mutagenic potency were used.
      This study firmly establishes that the predictive relationship between mutagenic
      potency in SAL and rodent carcinogenicity is, at best, weak. When predicting
      qualitative carcinogenicity, only qualitative mutagenicity is useful; none of the
      quantitative measures of potency considered improves the carcinogenicity
      prediction. In fact, when qualitative mutagenicity is forced out of the model,
      the quantitative measures are still not predictive of carcinogenicity. When
      predicting quantitative carcinogenicity, several possible methods were considered
      for summarizing potency over all experiments; however, in all cases, the
      relationship between mutagenic potency predictors and quantitative
      carcinogenicity is very weak.

PMID- 9142176
TI  - Synergistic effects of N-ethyl-N-nitrosourea (an alkylating agent with a low
      Swain-Scott substrate constant) and X-rays in the stamen hairs of Tradescantia
      clone BNL 4430.
AB  - The mutagenic interaction between N-ethyl-N-nitrosourea (ENU) and X-rays was
      tested in the stamen hairs of Tradescantia clone BNL 4430, a blue/pink
      heterozygote. ENU, a monofunctional alkylating agent with a low Swain-Scott
      substrate constant (s) of 0.26, exhibited a strong cytotoxicity. ENU-induced
      somatic pink mutation frequency per 10(4) hair-cell divisions increased with
      increasing ENU dose, with a slope of 1.243 on a log-log graph, the slope value
      being similar to that for X-ray-induced mutation frequency. Three out of five
      combined treatments with ENU and X-rays produced mutation frequencies
      significantly higher than those expected from the additive effects of the two
      mutagens. Clear synergistic effects were detected when relatively higher X-ray
      doses were applied, resembling those confirmed earlier between methyl
      methanesulfonate (MMS) and X-rays, although the s value for ENU is very much
      smaller than that (0.88) for MMS. It is therefore concluded that mutagenic
      interactions between alkylating agents and X-rays do not have any clear
      relationship with the s values.

PMID- 9142178
TI  - Genetic toxicity and carcinogenicity studies of Kathon.

PMID- 9142179
TI  - Locoregional techniques in the treatment of hepatic tumors.

PMID- 9142180
TI  - Roles of the transforming growth factor beta 1 and its type I and II receptors in
      the development of a pulmonary adenocarcinoma: results of an immunohistochemical
      study.
AB  - BACKGROUND: In the United States, pulmonary adenocarcinomas have recently
      replaced squamous cell carcinomas as the most frequent type of lung cancer
      encountered. The incidence of pulmonary adenocarcinoma continued to increase
      worldwide. METHOD: To determine the roles of the transforming growth factor-beta
      1 (TGF-beta 1), and TGF-beta type I receptor (T beta R-I), and the TGF-beta type
      II receptor (T beta R-II) in the progression of a pulmonary adenocarcinoma, their
      respective expressions have been immunohistologically studied in specimens from
      120 pulmonary adenocarcinoma patients. RESULT: The overall prognosis was
      significantly poorer for patients showing positive TGF-beta 1, T beta R-I, T beta
      R-II expressions than for patients who were negative to all three immunostainings
      (P < 0.01). Our multivariate analysis also revealed that a positive TGF-beta 1
      response significantly affect prognosis (P < 0.05). CONCLUSIONS: TGF-beta 1, T
      beta R-I, and T beta R-II play important roles in tumor progression, and a
      positive TGF-beta 1 expression can serve as a pulmonary adenocarcinoma marker. T
      beta R-I and T beta R-II expressions are necessary for TGF-beta signal
      transduction.

PMID- 9142181
TI  - Intralesionally implanted cisplatin cures primary brain tumor in rats.
AB  - BACKGROUND AND OBJECTIVES: Chemotherapy has added little to the overall survival
      of the patients with primary malignant brain tumors, primarily due to its
      difficulty penetrating the blood-brain barrier. Use of polymers, releasing high
      doses of chemotherapy locally over time, is a promising new treatment strategy.
      Three experiments were conducted to test the effect of cisplatin, released from
      biodegradable polymer, on rats with 1 week established brain tumor. METHODS: 9L
      gliosarcoma cells and drug-free or cisplatin-loaded polymer were administered
      through a right frontal lobe cannula in male Fischer 344 rats. Tumor cells were
      infused on day 0 and polymer on day 7. Animals were monitored for 60 days.
      RESULTS: In experiment one, 0.5 mg/m2 of cisplatin loaded in polymer resulted in
      a mean survival time (MST) of 51 +/- 14 days with 63% (10/16) rats surviving to
      day 60. MST for the control group was 24 +/- 4 days (p = 2.5 x 10(-9)). Evidence
      of clinical or histologic brain toxicity was minimal. In a second experiment,
      using drug-free polymer (n = 7), MST was 24 +/- 3 days. This was compared against
      an MST of 24 +/- 4 days in the tumor control group (n = 7) and 49 +/- 7 days in a
      cisplatin-polymer treated group (n = 6). In a third experiment, two doses of drug
      free polymer and three doses of cisplatin-loaded polymer were tested in normal
      nontumor-bearing rats and found to be well tolerated. CONCLUSIONS: Intralesional
      sustained release of cisplatin from biodegradable polymer is safe and effective
      for the treatment of brain 9L gliosarcoma in rats.

PMID- 9142182
TI  - Surgical Treatment of sacrococcygeal chordoma.
AB  - BACKGROUND: Sacrococcygeal chordomas are difficult to manage. METHODS: The
      treatment results of 12 patients with sacral chordomas were analyzed. Four
      patients had local relapse before they were referred to our hospital: three
      patients previously underwent two surgeries, and one patient one surgery and
      irradiation (60 Gy). In this institute, 10 patients underwent surgery alone, and
      one had surgery plus postoperative irradiation. One patient underwent
      radiotherapy alone due to an inoperable lesion that reached to the L5 spine. For
      seven surviving patients, the average follow-up period was 50 months. RESULTS:
      One of four patients with a marginal margin and one of two patients with a
      contaminated margin developed local relapse. Of five patients with intralesional
      margins, four patients developed local relapse and two had metastasis to the
      spine and lungs 36 and 15 months after surgery, respectively. One patient with
      irradiation alone had metastasis to the lungs 15 months after initiation of
      treatment. Three patients died due to progression of the disease, one of a heart
      problem and one of apoplexy. One of 10 patients with implantation of gentamycin
      beads after removal of tumor, developed infection. CONCLUSIONS: For local control
      of sacral chordomas, an adequate surgical margin is important. Gentamycin beads
      may be effective to control postoperative infection of the dead space.

PMID- 9142183
TI  - Intratumoral heterogeneity in primary breast carcinoma: study of concurrent
      parameters.
AB  - BACKGROUND AND OBJECTIVE: Intratumoral heterogeneity for prognostic factors
      (ploidy, proliferation, hormone receptor positivity) has been demonstrated in
      primary breast carcinoma by both flow cytometric and image analysis methods.
      Previously, heterogeneity in tumors had been demonstrated for only singular
      parameters. Our objective, using maps of tumors in which discrete regions can be
      analyzed simultaneously for DNA index (DI) and proliferative activity, was to
      demonstrate heterogeneity with respect to two parameters and to determine whether
      any interparametric relationships existed. METHODS: We analyzed 25 cases of
      archived, paraffin-embedded breast carcinoma (ductal) for Feulgen stain DNA
      analysis and MIB-1 immunohistochemistry using the CAS 200 Image Cytometer. For
      each tumor, four discrete regions were analyzed including tumor-host tissue
      interface sectors. RESULTS: Of 25 cases, 19 (76%) were homogeneously diploid or
      near-diploid aneuploid, and 6 (24%) were heterogeneous. Within the heterogeneous
      group, all cases had at least one diploid and one or more aneuploid populations
      from separate discrete regions. Five of six DI heterogeneous tumors displayed
      diploid values for the overall measurements of the respective tumors, based on
      analysis of 200 or more nuclei. Eight of 25 cases (32%) showed significant
      measurable variation for MIB-1 proliferative activity in various sectors of
      tumor. All the MIB-1 heterogeneous tumors, with one exception, were homogeneously
      diploid. CONCLUSIONS: These findings demonstrate that (1) heterogeneity is
      present with respect to DI and proliferative activity in breast carcinoma and is
      relatively common, (2) tumors homogeneous for one parameter may be heterogeneous
      for another, and (3) heterogeneity for proliferative activity is more common in
      homogeneously diploid tumors than in heterogeneous/aneuploid tumors.

PMID- 9142184
TI  - Gene therapy for colon cancer with the herpes simplex thymidine kinase gene.
AB  - BACKGROUND: The suicide gene and prodrug, herpes simplex thymidine kinase (HStk)
      and ganciclovir (GCV), are now in clinical trials for recurrent malignancies.
      METHODS: We evaluated in vitro and in vivo efficacy of HStk gene transfer and GCV
      treatment of colonic adenocarcinoma in a syngeneic murine model. RESULTS: In
      vitro analysis demonstrated that CT-26 adenocarcinoma cells transduced with
      LTKOSN.2 retroviral vector inhibited the proliferation of wild-type CT-26
      (nontransduced) cells after GCV exposure. Cooperative killing with HStk gene
      therapy was shown in vivo, mixtures of HStk CT-26 transduced cells (CT-26 TK),
      and nontransduced (CT-26 NV) cells and tumors containing only 9% CT-26 TK cells
      demonstrated complete regression after GCV (100 mg/kg). CONCLUSIONS: This in
      vitro and in vivo demonstration suggests that metabolic cooperation permits
      destruction of tumors even when gene transfer is effective only to a relatively
      small portion of the tumor. These important results suggest new avenues can be
      developed for the treatment of this lethal malignancy.

PMID- 9142185
TI  - Report of 337 patients with renal cell carcinoma emphasizing 110 with stage IV
      disease and review of the literature.
AB  - BACKGROUND: In the literature, the interdependence of variables, including stage,
      sex, age, tumor size, therapy, and survival, is complex. The size variable has
      heretofore received relatively little emphasis. METHOD: This was a retrospective
      evaluation of 337 patients with kidney cancer treated at the University of
      Illinois Affiliated Hospitals. Data were collected on stage, sex, age, tumor
      size, TNM stage, therapy, and survival. Statistical analyses included Kaplan
      Meier 5-year survivals, as well as multivariate analysis utilizing the Cox
      regression model. A subset of 110 patients with TNM Stage IV disease is further
      evaluated employing a multivariate analysis. The principal form of therapy was
      nephrectomy. RESULT: Five-year survivals by stage varied from 100% for Stage I,
      96% for Stage II, 59% for Stage III, to 16% for Stage IV. In the subset of 110
      patients with TNM Stage IV disease, those with a single metastasis had better
      survivals than those with two or more. Those having nephrectomy had better
      survivals (P < 0.05). Therapy (in addition to nephrectomy) was curative (defined
      as cytotoxic chemotherapy or immunotherapy) in 40 patients and palliative
      (defined as radiation to bone metastases, hormone therapy, or supportive) in 70
      patients. Multivariate analysis of TNM Stage IV variable differences indicated
      that only tumor size differences and nephrectomy significantly affected survival.
      CONCLUSIONS: Of importance is the observation that among these patients. Survival
      is directly correlated with tumor size.

PMID- 9142186
TI  - Long-term survival and DNA ploidy in advanced epithelial ovarian cancer.
AB  - BACKGROUND AND OBJECTIVES: The relationship of the tumor DNA content to survival
      of patients with advanced epithelial cancer has not yet been clarified. A large
      amount of contradictory data exists in the literature. This study analyzes the
      putative relationship between ploidy and advanced ovarian carcinoma. METHODS: A
      retrospective analysis of tumor ploidy, DNA index, and the S-phase fraction from
      35 patients with nonborderline epithelial ovarian carcinomas was determined by
      flow cytometry of paraffin-embedded tissue. All patients had FIGO stage III or IV
      disease. Those patients who survived > 5 years were assigned to Group A (10
      patients). Group B consisted of 25 age-matched subjects who succumbed to their
      disease within 5 years of diagnosis. RESULTS: Group A had not reached a median
      overall survival with a median follow-up of 114 months (range 67-226), whereas
      Group B had a median overall survival of 17 months (range 1-48). Two of the
      patients in Group A and all of the patients in group B had died of the disease.
      The two groups were similar in age, histologic type, and treatment. In Group A,
      three patients had grade 1 tumors, in contrast to group B where all the patients
      had either grade 2 or 3 disease (P = 0.018). However, the distribution of
      aneuploidy was similar in both groups. Also, the DNA indices were similar: 1.40
      +/- 0.42 in Group A, and 1.36 +/- 0.44 in Group B. The median S-phase fraction
      was 14% (range 3-23%) in Group A, and 15% (range 2-23%) in Group B. The grade and
      type of tumor were not related to the ploidy or the DNA index. There was no
      significant correlation between ploidy or the DNA index and survival. CONCLUSION:
      This study suggests that the DNA content of tumor as measured by flow cytometry
      is not a predictor of long-term survival in ovarian cancer patients with advanced
      disease.

PMID- 9142187
TI  - Synchronous multiple colorectal adenocarcinomas.
AB  - BACKGROUND: The object of the present work was to characterize clinical features
      and the quality of preoperative examinations in patients with synchronous
      colorectal carcinomas, and to compare the incidence of associated benign polyps
      with our findings in patients with a single malignant lesion. METHODS: A
      retrospective evaluation of 225 patients with primary colorectal carcinoma
      revealed 9 cases (4.0%) of synchronous colorectal carcinomas. RESULTS: The
      synchronous colorectal carcinomas were located in the same anatomical segment in
      7 patients and were divided into different segments in 2 patients. The accuracy
      of preoperative diagnosis was 55.6% by endoscopy alone and 66.7% by double
      contrast barium enema (DCBE) alone, while the rate was 77.8% when colonoscopy and
      DCBE were combined. There was a higher incidence of associated benign polyps in
      the group with synchronous colorectal carcinomas (55.6%) versus 28.7% for a
      single carcinoma (P < 0.05). The main reason why multiple lesions could not be
      identified preoperatively was that the distal lesions prevented examination of
      the proximal lesions. CONCLUSIONS: At the time of surgical resection, it is
      important to ascertain preoperatively whether or not a second lesion exists. If
      synchronous polyps are present in patients with synchronous colorectal
      carcinomas, they should be ablated to reduce the risk of metachronous colorectal
      carcinoma.

PMID- 9142188
TI  - Malignant pericardial effusion in breast cancer: terminal event or treatable
      complication?
AB  - BACKGROUND: Few data are available on malignant pericardial effusion (MPCE) in
      breast cancer. We identify the patient prone to develop MPCE describe the result
      of surgical management, and try to identify a subgroup of patients who do not
      benefit from surgical management. METHOD: We performed an audit of our policy of
      active search for MPCE in breast cancer patients and its treatment by subxiphoid
      pericardial fenestration. RESULT: Nineteen patients with MPCE had a mean of 3.2
      other sites of recurrence: 17 had pleural recurrence. Six patients had exertional
      dyspnea and 13 had dyspnea at rest; three needed emergency pericardiocentesis. An
      average of 740 ml of fluid was recovered; cytology was diagnostic in 11 cases and
      histopathology in 10 cases. At discharge, six patients had no dyspnea and six had
      exertional dyspnea. Of 10 patients who did not receive systemic treatment, eight
      died within 30 days. Nine patients who received systemic treatment had an average
      survival of 8.3 months. CONCLUSIONS: Patients with pleural recurrence presenting
      with dyspnea should be evaluated for the presence of a MPCE. Subxiphoid
      pericardial fenestration is the treatment of choice. Patients who will not
      receive systemic treatment should be managed conservatively.

PMID- 9142189
TI  - Assessment of rectal tumor infiltration utilizing endorectal MR imaging and
      comparison with endoscopic rectal sonography.
AB  - BACKGROUND: The preoperative assessment of depth of invasion of rectal carcinoma
      is increasingly important as new treatment methodologies are developed. Accuracy
      of preoperative endorectal MR imaging was therefore compared with that of the
      endoscopic rectal sonography in determining depth of invasion of rectal
      carcinomas. METHOD: From March 1993 to April 1994, 10 consecutive patients with
      biopsy-proven rectal carcinomas were imaged with both endorectal MR imaging and
      endoscopic rectal sonography. These two studies were performed an average of 2.7
      days apart in each patient. All 10 patients had surgical resection of the rectal
      carcinoma within days of imaging studies. TNM staging of each malignant lesion
      was correlated with the imaging reports. RESULT: Staging accuracy was 80% for
      endorectal MR imaging and 70% for endoscopic rectal sonography. With MR imaging,
      one T2 lesion was overstaged and one T3 lesion was understaged. With sonography,
      two T2 lesions were overstaged and one T3 lesion was understaged. One MR error
      resulted from misinterpretation. All other staging errors occurred in patients
      with tumor spread into, but not through, the muscularis propria or with
      microscopic spread through this layer. CONCLUSIONS: Endorectal MR imaging and
      endoscopic rectal sonography have similar accuracy for assessing depth of
      invasion of rectal carcinoma.

PMID- 9142191
TI  - Adverse effects of intraportal chemotherapy on natural killer cell activity in
      colorectal cancer patients.
AB  - BACKGROUND: Adjuvant intraportal chemotherapy has been used with a view to
      prevent the development of metachronous hepatic metastases following curative
      resection for colorectal cancer. To evaluate the effects of this therapy on
      systemic antitumor immunological activity, 35 colorectal cancer patients who
      underwent curative resection were investigated. METHOD: Among them. 19 had
      adjuvant intraportal chemotherapy with mitomycin C and 5-fluorouracil (treated
      group) and 16 had no chemotherapy (untreated group). Natural killer (NK) cell
      activity, lymphocyte subpopulations, and immunosuppressive acidic protein (IAP)
      in the peripheral blood were measured serially before and after operation, and
      the values were compared between the two groups. RESULTS: The NK cell activity
      and the percentages of CD16 positive and CD56 positive cells were markedly
      reduced in the treated group postoperatively. Significant difference was also
      observed between the two groups on the 4th postoperative day in regard to NK cell
      activity and CD56 positive cells. CONCLUSIONS: Intraportal chemotherapy in our
      study reduced the NK cell activity and its population in the peripheral blood.

PMID- 9142190
TI  - Phase II study of a modified combination of etoposide, doxorubicin, and cisplatin
      for patients with advanced gastric cancer.
AB  - BACKGROUND: Based on the promising results of EAP (etoposide, doxorubicin, and
      cisplatin) combination, a phase II study of modified EAP combination was
      performed in patients with advanced gastric cancer to evaluate the response,
      toxicity, and survival. METHOD: Fifty-two consecutive patients with measurable or
      evaluable advanced gastric cancer, who had no prior therapy except surgery, were
      treated every 28 days with etoposide 120 mg/m2/day, doxorubicin 25 mg/m2/day, and
      cisplatin 40 mg/m2/day on days 1 and 8, intravenously. Forty-seven patients were
      evaluable for response and toxicity. RESULTS: Overall response rate was 40.5%
      (95% CI = 37-54.7%), including 12.8% complete response. Responses were higher in
      patients with locally advanced disease (57.89%) as compared to those with distant
      metastases (28.57%) (P = 0.044). The median overall survivals of the entire group
      and the responders were 7 months and 11 months, respectively. Complete responders
      had significantly longer response duration and overall survival (31.5 months and
      45.5 months, respectively), as compared to partial responders (6 months and 9
      months, respectively). Six of the responders (31.6%) were alive at 2 years.
      Disease extension and pretreatment performance status had significant effects on
      survival. Grade 3-4 toxicity was observed in 33% of patients. There were no
      deaths related to toxicity. CONCLUSIONS: EAP as used in this trial is an
      effective treatment in advanced gastric cancer. The effect is more pronounced in
      patients with locally advanced disease.

PMID- 9142192
TI  - Cisplatin-based chemotherapy in advanced seminoma: experience of the Northern
      Israel Oncology Center: 1981-1994.
AB  - BACKGROUND: The efficacy of cisplatinum combined chemotherapy modalities was
      investigated in a variety of trials for patients with advanced seminoma. Results
      regarding remission rates and survival are encouraging. METHODS: Between December
      1981 and January 1994, 13 patients with either relapsed (following radiotherapy
      failure) or primarily advanced seminoma were treated with cisplatin-based
      chemotherapy at the Northern Israel Oncology Center. RESULTS: Eleven (84%)
      patients achieved complete clearance of all sites of disease. One patient
      demonstrated clinically and radiographically remarkable shrinkage of an abdominal
      mass, and laparotomy revealed fibrotic/necrotic tissue without viable tumor
      cells. After a mean follow-up of 58 months (range 4-168), 12 patients (92%) are
      alive and well without evidence of malignancy. One patient, in whom a 2-cm
      abdominal mass is stable radiographically, is under observation with no sign of
      tumor activity. Side effects were tolerable; no patient developed chemotherapy
      induced sepsis. One patient developed spontaneous pneumothorax a few days after
      completion of his first chemotherapy cycle, which resolved with treatment.
      CONCLUSIONS: Our results confirm the efficacy and safety of cisplatin-based
      chemotherapy in the treatment of advanced seminoma, even in pre-irradiated
      patients.

PMID- 9142193
TI  - Multiple lymphomatous polyposis.
AB  - Multiple lymphomatous polyposis (MLP) is a distinctive and particularly rare
      clinical type of malignant gastrointestinal lymphoma, which is classified as B
      cell centrocytic non-Hodgkin's lymphoma. this rare entity has been recently
      reclassified as mantle cell lymphoma. We herein report three additional cases of
      MLP involving various segments of the gastrointestinal tract. MLP has an
      aggressive biologic behavior and a relatively poor prognosis and must be treated
      accordingly as a high-grade lymphoma with systemic chemotherapy.

PMID- 9142194
TI  - Primary intrahepatic biliary cystadenomatous tumors.
AB  - BACKGROUND: Biliary cystadenoma and cystadenocarcinoma are rare tumors. The
      clinical features of, and optimal surgical management for these lesions have not
      been defined clearly. In this report, we describe three cases of cystadenomatous
      tumors of the biliary tract: two of a cystadenoma and one of a
      cystadenocarcinoma. The differential diagnosis of the cystic tumors of the liver
      in countries with a high prevalence of liver hydatid disease is very important.
      METHODS: The authors report their institution's experience from 1988 to 1995 in
      treating two cystadenomas and one cystadenocarcinoma and review previously
      reported cases in the literature. RESULTS: Clinical presentation is usually mild
      and atypical. During operation, the mass was resected en bloc with a margin of
      normal liver tissue in the cases of cystadenomas and, in the case of
      cystadenocarcinoma, a left hepatectomy with drainage of the common bile duct was
      performed. The two patients with adenomas remain well at 1 and 7 years after
      operation and our patient with adenocarcinoma is free of disease 8 years later.
      CONCLUSIONS: The treatment of choice is radical excision of the mass, either with
      a wide margin of normal liver or by means of a typical lobectomy, depending on
      the size and location of the lesion. When the lesion can be removed completely,
      the prognosis is excellent.

PMID- 9142195
TI  - Granulocyte colony-stimulating factor and interleukin-6-producing lung cancer
      cell line, LCAM.
AB  - BACKGROUND AND OBJECTIVES: We describe a case of granulocyte colony-stimulating
      factor (GCSF) and interleukin-6 (IL-6)-producing lung cancer. METHODS: A 53-year
      old man underwent left upper lobectomy under diagnosis of lung cancer. The tumor
      obtained by a preoperative biopsy was analyzed. RESULTS: Preoperative data showed
      leukocytosis with left-shift of leukocytic morphology and thrombocytosis and an
      elevated serum GCSF level. Histological examination revealed poorly
      differentiated adenocarcinoma. A cell line, named LCAM, was established from the
      tumor and the cytokines in the culture medium were measured by enzyme
      immunoassay. GCSF and IL-6 were produced in large amounts by LCAM, but
      granulocyte-macrophage colony-stimulating factor (GMCSF) and interleukin-3 (IL-3)
      were not. A proportion of LCAM expressed GCSF receptor on the cell surface, but
      IL-6 receptor could not be detected. LCAM proliferation was inhibited in the
      culture with antihuman GCSF antibody in a dose-dependent manner. CONCLUSIONS: We
      suggest that LCAM proliferation is positively regulated by GCSF.

PMID- 9142196
TI  - Diaphragmatic neurilemmoma: a histopathologic reappraisal.

PMID- 9142197
TI  - Spiral blade plate fixation for pathologic subtrochanteric femur fractures.

PMID- 9142198
TI  - Neuroblastoma screening in infants postponed after the sixth month of age: a
      trial to reduce "overdiagnosis" and to detect cases with "unfavorable" biologic
      features.
AB  - BACKGROUND: Encouraged by Japanese reports of the benefits of screening 6 month
      old infants for neuroblastoma, a neuroblastoma screening program was introduced
      in Austria in 1991. However, because of concerns related to "overdiagnosis" by
      screening at this age, the screening test was performed at a later age. METHODS:
      From March 1991 to February 1995 neuroblastoma screening was performed on filter
      paper urine specimens in 100,043 Austrian infants (median age 8.5 months).
      Primary analysis of urine catecholamines (vanillylmandelic acid and homovanillic
      acid was performed by use of an E1A method. Questionable or positive results were
      confirmed by high performance liquid chromatography (HPLC). A double retest was
      requested following a positive HPLC result. RESULTS: Twenty-one infants were
      admitted to a hospital following repeatedly elevated values of vanillymandelic
      acid (VMA) and/or homovanillic acid (HVA). Eleven infants were found to have
      neuroblastoma (three stage 1, four stage 2B, four stage 3). Treatment consisted
      of surgery alone with total or subtotal resection in eight cases, surgery and
      chemotherapy in two cases, and chemotherapy alone in one case. Biologic features
      were assessed in all tumors excluding ploidy in one case. The majority of the
      tumors analyzed were near-triploid (9/10), however, two tumors revealed N-myc
      amplification. CONCLUSIONS: Our results demonstrate that stage distribution and
      biologic features of neuroblastomas diagnosed by screening at 8.5 months are
      different from the results of screening at 6 months. Furthermore, the detection
      of one neuroblastoma among 9,100 screened infants is significantly lower than the
      incidence of the Japanese screening program. Our results suggest that screening
      at an age of 7 to 10 months reduces overdiagnosis and may be of more benefit than
      earlier screening.

PMID- 9142199
TI  - Chemotherapy-induced expression of alpha B-crystallin in neuroblastoma.
AB  - Since alpha B-crystallin is known to be expressed in glial tissues of human brain
      and neuroectodermal tumors, the alpha B-crystallin content of neuroblastomas, may
      be related to the degree of glial or neuronal differentiation. The alpha B
      crystallin content of 73 neuroblastomas, was determined by enzyme immunoassay.
      The concentration of alpha B-crystallin was examined in light of neuroblastoma
      prognostic factors. Neuroblastomas from patients who received chemotherapy (n =
      23) contained higher concentrations of alpha B-crystallin than those from
      patients who did not receive chemotherapy (n = 50) (P > 0.05). There was a
      statistically significant difference in alpha B-crystallin concentrations in
      advanced stage patients who received preoperative chemotherapy (P < 0.01).
      Immunohistochemistry demonstrated alpha B-crystallin expression in the nerve-like
      fibers and a few ganglion-like cells. Staining was not apparent in the less
      differentiated cells in the tumor cell nest. alpha B-crystallin may play a role
      in the response to cellular stress in neuroblastoma.

PMID- 9142200
TI  - Importance of the day 7 bone marrow biopsy as a prognostic measure of the outcome
      in children with acute lymphoblastic leukemia.
AB  - The presence of > or = 25% blasts in a marrow aspirate obtained on day 7 of
      induction followed by a remission at day 28 has been associated with a poor
      prognosis in children with acute lymphoblastic leukemia (ALL). We evaluated
      whether a day 7 marrow biopsy may be used to more accurately assess therapeutic
      reduction of leukemia tumor burden. Studied were 76 children with ALL enrolled on
      CCG protocols at B.C's Children's Hospital who received both a day 7 aspirate and
      biopsy and were in remission by day 28. Evaluation for the correlation of the
      percentage aspirate blasts on day 7 with the biopsy demonstrated a moderate
      correlation with the percentage biopsy blasts (R = 61), but not correlation with
      the biopsy cellularity. We saw a similar prediction of outcome by the percentage
      blasts on day 7 marrow aspirate in the study as reported previously although it
      was not significant. Outcome analysis was done using leukemia burden as measured
      by the day 7 absolute blast index-aspirate (ABI-aspirate) calculated as the
      product of the biopsy cellularity with the percentage blasts on the aspirate. The
      ABI-aspirate significantly predicted patient outcome with 83% survival in those
      with an ABI-aspirate of < .06 compared to 51% in those > or = .06 (P = .01) and
      was highly significant when analyzed as a continuous predictor (P = .004). This
      is the first study to demonstrate that information gained from the day 7 marrow
      biopsy can improve prediction of outcome in children with ALL. Based on this
      preliminary study, we recommend that large population ALL therapy trials evaluate
      the role of the day 7 marrow biopsy for outcome prediction in children with ALL.

PMID- 9142201
TI  - Treatment of Hodgkin's disease in children with alternating mechlorethamine,
      vincristine, procarbazine, and prednisone (MOPP) and adriamycin, bleomycin,
      vinblastine, and dacarbazine (ABVD) courses without radiotherapy.
AB  - Since the introduction of mechlorethamine, vincristine, procarbazine, and
      prednisone (MOPP) chemotherapy, children with Hodgkin's disease (HD) have been
      treated with chemotherapy alone. The occurrence of side effects related to
      irradiation (especially secondary solid tumors) is less likely to occur.
      Alkylating agents in the MOPP chemotherapy combinations are, however, known for
      their late effects, i.e., gonadal dysfunction and secondary malignancies.
      Combination with non-alkylating and non-cross-resistant drugs (as in the
      adriamycin, bleomycin, vinblastine, and dacarbazine [ABVD] combination: may give
      superior treatment results and possibly a decrease in the occurrence of side
      effects. From 1988 to 1993 all children presenting with HD were treated with
      alternating MOPP and ABVD courses (3 x MOPP, 3 x ABVD). Twenty-one children (7
      females, 14 males), ages 5-18 years (median 14 years) were included; their
      clinical stages were 1, 7 patients; II, 8 patients; III, 5 patients; IV, 1
      patient. Their pathology revealed 2 lymphocytic predominance, 17 nodular
      sclerosis, 1 mixed cellularity. In 1 patient only cytology was done and thus
      histopathologic subclassification was not possible. Two children have relapsed;
      disease-free survival is 90%. Analysis of toxicity revealed no decrease in
      cardiac function by ultrasound examination and no pulmonary effects noted by
      carbon monoxide diffusion. In 1 of the 10 children tested, mild hypogonadism was
      noted. No secondary tumors occurred. From this small population of children with
      HD we conclude that treatment with MOPP/ABVD for 6 cycles without radiotherapy
      may be adequate. The occurrence of gonadal dysfunction may be less frequent than
      with 6 cycles of MOPP. However, more patients and further follow-up are needed.

PMID- 9142202
TI  - Phase II study of daily oral etoposide in children with recurrent brain tumors
      and other solid tumors.
AB  - Pre-clinical data and adult experience suggests that topoisomerase targeted anti
      cancer agents may be highly schedule dependent, and efficacy may improve with
      prolonged exposure. To investigate this hypothesis, 28 children with recurrent
      brain and solid tumors were enrolled in a phase II study of oral etoposide (ETP).
      Patients were prescribed ETP at 50 mg/m2/ day for 21 consecutive days. Courses
      were repeated every 28 days pending bone marrow recovery. Evaluation of response
      was initially performed after 8 weeks and then every 12 weeks either by CT or
      MRI. Three of 4 patients with PNET (primitive neuroectodermal
      tumor)/medulloblastora achieved a partial response (PR). Two of 5 with ependymoma
      responded, one with a complete response and one with a PR. Toxicity was
      manageable with only 1 admission for fever and neutropenia in 120 cycles of
      therapy. Five patients had grade 3 or 4 neutropenia. One had grade 4
      thrombocytopenia and one grade 2 mucositis and withdrew as a result. One patient
      had grade 2 diarrhea. Two patients who achieved a PR had received ETP as part of
      prior combination chemotherapy regimens. Daily oral etoposide is active in
      recurrent PNET/medulloblastoma and ependymoma. Toxicity is manageable and rarely
      requires intervention. Daily oral etoposide in combination with crosslinking
      agents should be considered in future phase III trials. Determination of activity
      in glioma and solid tumors is not complete.

PMID- 9142203
TI  - Optic chiasm glioma, electrolyte abnormalities, nonobstructive hydrocephalus and
      ascites.
AB  - A 4-year-old girl with optic chiasm glioma (OCG), nonobstructive hydrocephalus
      and ventriculoperitoneal shunt is described, in whom marked ascites developed.
      The ascitic fluid was protein-rich and its amount correlated with cerebrospinal
      fluid (CSF) protein. The CSF protein level and the amount of ascitic fluid were
      influenced by chemotherapy. Very unusual hypernatremia, up to 190 mEq/l with no
      associated alteration in mental status, was also found. It is suggested that
      altered absorption ability owing to the high protein content was the cause of
      both the nonobstructive hydrocephalus and the ascites. The unusual well being
      with very high sodium concentrations may have resulted from osmoreceptor
      dysfunction, presumably caused by hypothalamic involvement as well as by the high
      CSF protein. This combination of findings may point toward specific
      characteristics of OCG. In an effort to reduce the amount of the ascitic fluid, a
      further chemotherapeutic trial may be done, before converting the shunt to the
      vetriculoatrial system.

PMID- 9142204
TI  - Diabetes insipidus secondary to Langerhans' cell histiocytosis: is radiation
      therapy indicated?
AB  - Langerhans' cell histiocytosis (LCH) is a proliferative disease of Langerhans'
      cells that has multiple clinical manifestations including diabetes insipidus
      (DI). This study reviews the effectiveness of hypothalamic-pituitary radiation
      therapy (HPRT) as a treatment of LCH-induced DI in the modern era. A
      retrospective review was done of 116 pediatric patients with LCH seen from 1975
      to 1992. Seventeen of the 116 patients (15%) were diagnosed with complete or
      partial diabetes insipidus. Diagnosis was made either by water deprivation test
      or on clinical grounds. Fourteen patients received hypothalamic-pituitary
      irradiation as treatment for DI. The median interval from the onset of DI
      symptoms (polyuria and polydipsia) to treatment was 30 days. The median interval
      from the onset of diagnosis to treatment was 4 days. With a mean follow-up of 7.3
      years (range, 2.4-14.3), only two patients had a complete response to therapy, as
      defined as no need for antidiuretic hormone (ADH) replacement therapy. No patient
      had a partial response, defined as a decrease in the dose of ADH replacement. Of
      the two responders, neither had a complete ADH deficiency, suggesting "early"
      disease. In addition, both received RT within 3 days. We feel that the standard
      treatment of RT to all patients with LCH-induced DI is no longer justified. Our
      series has shown no benefit in treating patients with a long history of DI.
      Rather, an improved rationale would be rapid initiation of hypothalamic-pituitary
      irradiation in patients with new symptoms of DI and an abnormal water deprivation
      test.

PMID- 9142205
TI  - Relapse of intracranial germinoma 23 years postirradiation in a patient given
      growth hormone replacement.
AB  - There is no clear evidence that growth hormone replacement therapy for treatment
      related growth hormone deficiency in patients with childhood intracranial
      malignancies has a role in tumour relapse or second malignancy. A 16-year-old
      girl with an intracranial germinoma was treated with local radiotherapy and
      subsequently received growth hormone replacement therapy as an adult. Three years
      after starting growth hormone therapy, 23 years after her radiotherapy treatment,
      the patient's tumour recurred. Surveillance requirements for patients receiving
      growth hormone in this setting are discussed.

PMID- 9142206
TI  - Delayed-accelerated hyperfractionated radiation therapy for advanced-stage or
      high-risk rhabdomyosarcoma.
AB  - The treatment of six patients with advanced-stage or high-risk rhabdomyosarcoma
      (RMS) is described. These patients were treated with a delayed-accelerated
      hyperfractionated radiation therapy (DAHFRT) regimen which delivers 5200 cGy over
      20 treatment days. Acceptable early toxicity was noted when radiation therapy was
      given after a full course of chemotherapy and major attempts at resection of the
      primary tumor. The DAHFRT regimen has inherent biological and time-intensity
      advantages compared to other fractionation schemes which may be exploited to
      improve local control. The DAHFRT regimen should be considered as an alternate
      fractionation scheme for RMS patients and a possible foundation from which dose
      escalation of radiation therapy may be attempted using advanced treatment
      planning technology. Late effects of high-dose radiation therapy, although a
      major concern, should assume less priority given the high local failure rates of
      advanced-stage patients and the advent of conformed radiation therapy treatment
      planning and delivery which can be used to reduce treatment-related toxicity.

PMID- 9142207
TI  - Orbital rhabdomyosarcomas and related tumors in childhood: relationship of
      morphology to prognosis--an Intergroup Rhabdomyosarcoma study.
AB  - Children and adolescents who develop rhabdomyosarcoma (RMS) and related sarcomas
      in the orbit and treated on Intergroup Rhabdomyosarcoma protocols have had an
      extremely high cure rate. This study evaluates the possible relationship between
      their tumor morphologic subtypes and this high cure rate. The histology of tumors
      was re-reviewed from 229 of the 264 patients with tumors of the orbit,
      conjunctiva, and eyelids treated on Intergroup Rhabdomyosarcoma Studies (IRS I,
      II, III, and IV pilot protocols, and followed through July, 1992.
      Immunohistochemistry was applied in selected cases. Clinical correlations were
      done on all 264 cases including both the re-reviewed cases and those reviewed
      only by the IRS Pathology committee. The 5-year survival rate of 24 children with
      alveolar RMS was 74% (p < .001). All five infants diagnosed to have an alveolar
      RMS died before the age of one. Two hundred and twenty-one patients (84%) had
      embryonal RMS. About three-fourths of the re-reviewed embryonal RMS tumors showed
      only minimal rhabdomyoblastic differentiation. Thirty-one had a spindle cell RMS,
      two were anaplastic variants. The 5-year survival rate for patients with
      embryonal RMS subtypes combined was 94%, and 97% for the 144 patients with poorly
      differentiated embryonal RMS. In contrast, 90 of 432 IRS II patients treated for
      poorly differentiated embryonal RMS located in extraocular sites had a 66%
      survival estimate.

PMID- 9142208
TI  - Case of extra pulmonary, pleuro-pulmonary blastoma in a child: pathological and
      cytogenetic findings.
AB  - We report the cytogenetic findings in a case of Pleuro-Pulmonary Blastoma of
      Childhood Type II. This is a rare intrathoracic tumour that can occur in the
      lungs with up to 25% of cases being extra pulmonary.

PMID- 9142209
TI  - DNA-analysis is mandatory in case of an uncommon malignancy.
AB  - In a child a diagnosis of sweat gland carcinoma was made on basis of a surgical
      specimen presumed to be taken from an occipital lymph node. DNA analysis
      confirmed mixing of specimens in the referring hospital.

PMID- 9142210
TI  - Late recurrence of a brain tumor.

PMID- 9142211
TI  - Re: SIOP Working Committee on Psychosocial Issues--guidelines for care of long
      term survivors.

PMID- 9142212
TI  - Aging and cancer: the role of stromal interactions with epithelial cells.

PMID- 9142213
TI  - Altered transcriptional regulation of the insulin-like growth factor 2 gene in
      human hepatocellular carcinoma.
AB  - The insulin-like growth factor 2 (IGF2) gene is regulated in a complex manner,
      involving developmentally regulated use of four different promoters as well as
      transcriptional repression of the maternal allele due to genomic imprinting. It
      has been well documented that liver is an exceptional organ in which overall
      transcription from the four IGF2 promoters is markedly imbalanced towards
      preferential paternal expression only in fetal life, this being relaxed during
      the postnatal period, resulting in biallelic expression thereafter. We previously
      reported a marked allelic-expression imbalance in the overall transcription of
      IGF2 in hepatocellular carcinoma (HCC), leading to preferential expression
      nonrandomly from the paternal allele. The study presented here, using 18 HCC
      specimens taken directly from patients, showed that this molecular change often
      reflects promoters switching from the adult P1 promoter to the fetal P2, P3, and
      P4 promoters. Interestingly, however, we found that restoration of allele
      specific expression of the P1 promoter nonrandomly from the paternal allele was
      also frequent in HCC suggesting retention of an imprint for paternal expression
      from the P1 promoter of IGF2 in adult normal liver and altered availability of
      its modifying factor or factors in HCC. Further studies of the molecular
      mechanisms involved in the fluctuation of promoter usage and genomic imprinting
      of IGF2 are warranted to gain an insight into the biology of the liver in terms
      of development and oncogenesis.

PMID- 9142214
TI  - Frequency of Ha-ras-1 gene mutations inversely correlated with furan dose in
      mouse liver tumors.
AB  - Liver tumors were induced in infant male B6C3F1 mice by preweaning administration
      of furan, either as a single dose of 400 mg/kg body weight or six doses of 200
      mg/kg body weight. Six doses of 200 mg/kg furan resulted in an increased
      incidence and multiplicity of liver tumors relative to the multiple-dose vehicle
      control group and the single-dose furan group. In the single-dose group, there
      was an increase in overall tumor multiplicity but not prevalence of liver tumors.
      After polymerase chain reaction amplification of isolated DNA, slot-blot
      oligonucleotide hybridization was used to screen for mutations at known
      mutational hot-spots in the first three exons of Ha-ras-1 (Hras1). The relative
      frequency of Hras1 activation was 82% in the 28 tumors analyzed from the single
      dose group and 32% in the 28 tumors analyzed from the multiple-dose group. The
      lack of histomorphologic evidence of chronic cytotoxicity in the livers and the
      pattern of Hras1 activation suggest that a genotoxic mode of action is
      responsible for at least part of the hepatocarcinogenicity of furan in B6C3F1
      mice. These findings confirm previously documented hepatocarcinogenicity of furan
      in B6C3F1 mice and provide evidence that carcinogen dose may influence the
      frequency of Hras1 activation in mouse liver tumors.

PMID- 9142215
TI  - Loss of heterozygosity at the N-ras locus in 7,12-dimethylbenz[a] anthracene
      induced rat leukemia.
AB  - The 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat leukemia model enables
      scientists to analyze cells altered by carcinogens at various stages of
      leukemogenesis. We have reported that a consistent type of point mutation. A-->T
      transversion at the second base in codon 61 of the N-ras gene, was present in
      this leukemia and that this mutation appeared in bone marrow cells as early as 48
      h after a single dose of DMBA. In addition, two leukemia cell lines with the N
      ras mutation had no wild-type N-ras allele. Therefore, we examined whether these
      alterations were essential to the DMBA-induced leukemias. In the study reported
      here, we confirmed the occurrence of this N-ras mutation in 18 (86%) of 21
      primary leukemias and loss of the N-ras wild-type allele in 12 (67%) of 18
      leukemias with the mutated N-ras. By using microsatellite markers on chromosome
      2, loss of heterozygosity (LOH) at the N-ras locus was observed in eight
      leukemias, all of which were shown to have lost the wild-type N-ras allele by
      mutant-allele-specific amplification. These results suggest that LOH related to
      loss of the wild-type N-ras allele reproducibly occurs in leukemias with the N
      ras mutation. Considering the timing of the N-ras mutation and LOH, it is likely
      that the N-ras mutation is induced early, and cells that have lost the wild-type
      N-ras allele seem to develop into leukemia. We believe that this system provides
      a suitable model for studying a series of genetic alterations from the earliest
      stage of carcinogenesis that cannot be approached in human malignancies.

PMID- 9142216
TI  - Downregulation of Waf1, C2, C3, and major histocompatibility complex class I loci
      within an 18-cM region of chromosome 17 in adenovirus-transformed mouse cells.
AB  - In this study, the expression of the p53 tumor suppressor gene and the p53
      regulated Mdm2 and Waf1 genes was evaluated in adenovirus (Ad)-transformed mouse
      cells. The expected levels of p53 mRNA and protein and Mdm2 mRNA were detected in
      all transformed cells. However, the level of Waf1 mRNA was markedly reduced in
      Ad12-transformed cells and in some Ad5-transformed cells. Waf1 expression was not
      reduced in untransformed mouse cells infected with Ad12 or Ad5. Expression of the
      class I major histocompatibility complex (MHC) locus was downregulated in 13 Ad
      transformed cell lines (derived from four different strains of mice) that
      exhibited reduced expression of Waf1. Waf1 is located on mouse chromosome 17
      proximal to the MHC class I locus. To determine whether other chromosome 17 genes
      were downregulated, the cells were examined for expression of other genetic loci.
      Of those tested, only the C2 and C3 complement loci were expressed in mouse
      fibroblasts. Expression of C2 (which is within the MHC) and expression of C3
      (which is 15 cM distal to the MHC) were downregulated in those transformed cells
      in which Waf1 and MHC class I were downregulated. The Ad12- and Ad5-transformed
      cells that expressed low levels of Waf1, MHC class I, C2, and C3 formed tumors in
      syngeneic adult mice. These data suggest that the downregulation of multiple
      genes within the 32 Mb of mouse chromosome 17 that includes the Waf1 locus to the
      C3 locus occurs in Ad mouse-cell transformation and may contribute to the
      tumorigenicity of transformed cells.

PMID- 9142217
TI  - Resistance to apoptosis induced by alkylating agents in v-Ha-ras-transformed
      cells due to defect in p53 function.
AB  - In this study, we examined the susceptibility of various oncogene-transformed
      NIH/3T3 cells to apoptosis induced by alkylating agents. Only v-Ha-ras
      transformed cells showed marked resistance to apoptotic death induced by these
      drugs. Upon treatment with methylmethane sulfonate (MMS), NIH/3T3 cells exhibited
      normal G1 checkpoint function accompanied by the accumulation of p53 and
      p21CIP1/WAF1 protein. However, no such effects were observed in v-Ha-ras
      transformed cells. To further examine the functional status of p53 in ras
      transformed cells, we determined the DNA sequence, protein half-life, protein
      complexing activity, and specific DNA-binding activity of p53. The results showed
      that ras transformants and parental NIH/3T3 cells had the same p53 protein half
      life of 40 min or less, the same normal wild-type p53 cDNA sequence, and the same
      coimmunoprecipitable cellular proteins complexed with p53. In electrophoretic
      mobility gel-shift assays, however, nuclear extracts of cells treated with MMS,
      ras-transformed cells, and normal cells displayed distinct patterns of binding
      between p53 and its consensus binding site. Furthermore, western blot analysis
      showed that the bcl-2 and bax proteins were constitutively elevated in ras
      transformed cells but not in parental NIH/ 3T3 cells. Heat-shock protein 70
      (hsp70), which has been found to be negatively regulated by wild-type p53, was
      also dramatically induced in ras-transformed cells but not in NIH/3T3 cells in
      response to MMS. Thus, our data suggest that an activated ras oncogene can
      suppress alkylating agent-induced apoptotic cell death by means of a defect in
      the signal transduction pathway regulating p53 function and alteration in the
      expression of apoptotic (bax) or anti-apoptotic proteins (bcl-2 and hsp70).

PMID- 9142218
TI  - Genetic alterations and oxidative metabolism in sporadic colorectal tumors from a
      Spanish community.
AB  - Deletions of loci on chromosomes 5q, 17p, 18q, and 22q, together with the
      incidence of p53 mutations and amplification of the double minute-2 gene were
      investigated in the sporadic colorectal tumors of 44 patients from a Spanish
      community. Chromosome deletions were analyzed by means of loss of heterozygosity
      analysis using a restriction fragment length polymorphism assay. Allelic losses
      were also detected by polymerase chain reaction (PCR)-single-stranded
      conformation polymorphism (SSCP) analysis of a polymorphic site in intron 2 of
      the p53 gene. The percentages of genetic deletions on the screened chromosomes
      were 39.3% (5q), 58.3% (17p), 40.9% (18q), and 40% (22q). Mutations in p53 exons
      2-9 were examined by PCR-SSCP analysis and direct sequencing of the mutated
      region. Twenty of 44 tumor samples (45.45%) showed mutations at various exons
      except for exons 2, 3, and 9, the most frequent changes being G-->T transversion
      and C-->T transition. Because oxygen-free radicals play a role in the
      carcinogenesis process, we evaluated the oxidative status of the colorectal
      tumors. Antioxidant activities, lipid peroxidation, and DNA-damaged product
      concentrations in colon tumors and normal mucosa were compared. In tumor tissues,
      superoxide dismutase and catalase decreased fourfold and twofold, respectively,
      whereas glutathione peroxidase and reduced glutathione increased threefold.
      Malondialdehyde and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were twofold
      higher in colorectal tumors than in normal mucosa. Seven of 10 DNA tumor samples
      (70%) showing higher values of 8-OHdG also had genetic alterations at different
      chromosomal loci. In these samples, the p53 gene was deleted or mutated in 71.4%
      of cases. We concluded that the observed changes in the oxidative metabolism of
      the tumor cells and the consecutive increase in DNA damage may potentiate the
      genomic instability of different chromosomal regions, leading to further cell
      malignancy and tumor expansion.

PMID- 9142219
TI  - Modifications of the hepatocyte growth factor/c-met pathway by constitutive
      expression of transforming growth factor-alpha in rat liver epithelial cells.
AB  - We have previously shown that rat liver epithelial cells (RLEC) transfected with
      and constitutively expressing transforming growth factor-alpha (TGF-alpha) have
      an enhanced mitogenic response to hepatocyte growth factor (HGF). In the study
      reported here, we examined tumor clones derived from the TGF-alpha transfectants
      with respect to mitogenic response to HGF. Tumor cell lines that expressed TGF
      alpha responded to HGF with a greater increase in DNA synthesis than did the
      nontransfected parental RLEC (pRLEC). The tumor clones had also acquired a lower
      threshold for HGF response, which enabled them to undergo significant DNA
      synthesis at a low concentration of HGF that did not evoke a response in the
      pRLEC or TGF-alpha transfectants. We investigated the mechanisms by which TGF
      alpha expression may influence the HGF/c-met pathway. We showed that most TGF
      alpha transfectants and tumor cells displayed increases in c-met mRNA and
      protein, indicating that the enhanced HGF response may be due in part to an
      increase in the amount of receptor present. However, in all transfectants and
      tumor clones that constitutively expressed TGF-alpha, c-met was tyrosine
      phosphorylated in the absence of ligand (HGF) or other exogenous growth factors.
      These data suggest that induction of c-met mRNA and transactivation of c-met may
      be a sequela of the constitutive expression of TGF-alpha and that constitutive
      activation of the epidermal growth factor receptor pathway leads to
      phosphorylation and activation of c-met. These studies provide evidence for a
      novel mechanism of communication between epidermal growth factor receptor and c
      met pathways that may partially explain the synergistic effects reported between
      TGF-alpha and HGF.

PMID- 9142220
TI  - Current status of the genetic and physical maps of the major histocompatibility
      complex in the rat.

PMID- 9142221
TI  - Clonal contigs of the class I regions of the rat major histocompatibility
      complex.

PMID- 9142222
TI  - Nucleotide sequences of rat cDNA clones coding heavy chain class I major
      histocompatibility complex proteins.

PMID- 9142223
TI  - Localization of tolerogenic epitopes in the alpha 1 helical region of the rat
      class I major histocompatibility complex molecule.

PMID- 9142226
TI  - Organization of RT1-DOa and RT1-DOb loci.

PMID- 9142225
TI  - Identification and differentiation of transcribed major histocompatibility
      complex class II RT1B alpha and RT1B beta alleles from laboratory rats.

PMID- 9142224
TI  - Markers for interspecies relationship in the RT1 complex.

PMID- 9142227
TI  - Heterogeneous V beta gene usage in mercury-induced immune disorders in rats.

PMID- 9142228
TI  - HgCl2 and IL4 differentially modify expression of major histocompatibility
      complex class II molecules RT1.B and RT1.D in B lymphocytes from brown Norway and
      Lewis rats.

PMID- 9142229
TI  - Congenic spontaneously diabetic hypertensive BB.SHR rats.

PMID- 9142230
TI  - Elevated intracellular glutathione levels in CD4+ T cells of BB rats.

PMID- 9142231
TI  - In vitro survival and RT6 expression kinetics in peripheral T cells of diabetes
      prone BB and Lewis rats.

PMID- 9142232
TI  - Induction of insulin-dependent diabetes mellitus in PVG.RT1u rats.

PMID- 9142233
TI  - Major histocompatibility complex haplotype RT1av1 is associated with
      relapsing/remitting experimental autoimmune encephalomyelitis.

PMID- 9142234
TI  - Separation of major histocompatibility complex (MHC) and non-MHC gene effects in
      the development of T cell subsets in relation to susceptibility to cyclosporine A
      induced autoimmunity.

PMID- 9142235
TI  - Comparative susceptibility of DA, LEW, and LEW.1AV1 rats to arthritis induced
      with different arthritogens: mineral oil, mycobacteria, muramyl dipeptide,
      avridine and rat collagen type II.

PMID- 9142236
TI  - Expression profiles of RT6 and other T lymphocyte surface markers in the black
      rat (Rattus rattus).

PMID- 9142237
TI  - Rat T cell differentiation alloantigens RT6.1 and RT6.2 are NAD(+)-metabolizing
      ecto-enzymes that differ in their enzymatic activities.

PMID- 9142238
TI  - Transcription of the gene for the rat T cell differentiation marker RT6 is mainly
      mediated by a promoter 5' of exon 2.

PMID- 9142239
TI  - Polymorphic microsatellite within the main promoter of the rat T cell
      differentiation antigen RT6 on chromosome 1.

PMID- 9142240
TI  - Rat CD1 antigen: structure, expression and function.

PMID- 9142241
TI  - Retinoic acid teratogenicity in rat congenic and recombinant inbred strains with
      malformation syndrome.

PMID- 9142242
TI  - Genetic quality testing of cell lines derived from laboratory rats by polymerase
      chain reaction.

PMID- 9142243
TI  - The time pattern of organ infiltration and distribution of natural killer cells
      and macrophages in the course of acute graft rejection after allogeneic heart
      transplantation in the rat.

PMID- 9142244
TI  - An in vitro model for studying the role of graft endothelial cells in rat heart
      allograft rejection: a study of the regulation and function of heart endothelial
      histocompatibility antigens and cell adhesion molecules.

PMID- 9142245
TI  - Effect of variable doses of antilymphocyte serum on T cell depletion and cardiac
      allograft survival.

PMID- 9142246
TI  - The role of alloantigen-independent factors in transplant arteriosclerosis.

PMID- 9142247
TI  - Acute rejection of rat renal allografts is influenced by the presence of a native
      kidney.

PMID- 9142248
TI  - Study of hepatocyte growth factor in cyclosporine-induced nephropathy.

PMID- 9142249
TI  - Primary nonfunction of islet xenografts in rat recipients results from non-T-cell
      mediated immune responses.

PMID- 9142250
TI  - Increased DNA fragmentation in isolated rat islets following 24 hour co-culture
      with cytokine transgene-bearing adenovirus is dose dependent, but does not reduce
      glucose-stimulated insulin secretion.

PMID- 9142251
TI  - Impact of RT1.C-encoded MHC antigens on host-versus-graft and graft versus-host
      reactions in a model of small bowel transplantation in the rat.

PMID- 9142252
TI  - Vascularized bone marrow allotransplantation in rats prolongs a simultaneous skin
      allograft.

PMID- 9142253
TI  - Genetic analysis of graft-versus-host disease using rat recombinant inbred
      strains.

PMID- 9142254
TI  - Inhibition of acute graft-versus-host disease in (LEW.1W x LEW.1A)F1 rats using 9
      (2-phosphonomethoxyethyl)-2,6-diaminopurine.

PMID- 9142255
TI  - Evidence that the adenoviral vector containing the CTLA4-Ig gene improves
      transgene expression and graft survival.

PMID- 9142256
TI  - Differential effects of cyclosporin-A and rapamycin on in vivo thymocyte
      maturation.

PMID- 9142257
TI  - Migratory properties of skin dendritic cells of the rat.

PMID- 9142258
TI  - In vivo activated rat monocytes up-regulate NKR-P1A and down-modulate CD4 and
      CD43.

PMID- 9142259
TI  - In vitro and in vivo gene transfer in the rat: characterization of recombinant
      adenoviral vectors for rat interleukin-4 or interleukin-10 cDNA.

PMID- 9142260
TI  - Identification of a novel rat B cell subset in the peritoneal cavity of
      xenogeneic rat to mouse SCID chimeras.

PMID- 9142261
TI  - Biological characteristics of spontaneous transplantable T-cell lymphomas in
      inbred Sprague-Dawley/cub rats.

PMID- 9142262
TI  - Recent advances in rat genomics.

PMID- 9142264
TI  - Application of mouse microsatellite markers to rat genome mapping.

PMID- 9142263
TI  - Rat embryonic stem cells: a progress report.

PMID- 9142265
TI  - Rat genome mapping using recombinant inbred strains.

PMID- 9142266
TI  - Map of the differential segment of rat chromosome 8 in the SHR-Lx congenic
      strain.

PMID- 9142267
TI  - Production of transgenic rats for human regulators of complement activation.

PMID- 9142268
TI  - Chromosome 13 of the rat (Rattus norvegicus).

PMID- 9142269
TI  - How heterozygous are wild rats (Rattus norvegicus)?

PMID- 9142270
TI  - Report of the second meeting of the International Rat Genetic Nomenclature
      Committee (RGNC) held on August 20, 1996 in Toulouse, France.

PMID- 9142271
TI  - Intestinal transplantation in pediatric patients: the European experience.

PMID- 9142272
TI  - Clinical intestinal transplantation: experience in Miami.

PMID- 9142273
TI  - Clinical intestinal transplantation: European experience in adults.

PMID- 9142274
TI  - The Italian need for intestinal transplantation.

PMID- 9142275
TI  - Experimental basis for intestinal transplantation.

PMID- 9142276
TI  - Cyclosporine causes an increase of contractile activity in rat small bowel.

PMID- 9142277
TI  - Cytokines are involved in the rejection of small intestine allografts.

PMID- 9142278
TI  - 21-Aminosteroid U-74389G (lazaroid) inhibits bacterial translocation after small
      bowel transplantation in rats.

PMID- 9142279
TI  - Allograft survival prolongation after microsurgical lymphatic reconstruction in a
      short-term immunosuppressed rat small bowel transplantation model.

PMID- 9142280
TI  - Postoperative enteral feeding improves mucosal morphometry and absorption of D
      xylose by intestinal allografts in pigs.

PMID- 9142281
TI  - Small bowel myoelectrical activity after transplantation in pigs: motility versus
      ACR score.

PMID- 9142283
TI  - Protective effect of pyruvate during acute rejection of intestinal allografts:
      accompanied by up-regulation of inducible nitric oxide synthase mRNA.

PMID- 9142282
TI  - Complement activation during rejection in experimental intestinal
      transplantation.

PMID- 9142284
TI  - Interaction between ischemia/reperfusion-induced leukocyte emigration and
      translocating bacterial enterotoxins on enteric muscle function.

PMID- 9142285
TI  - Small bowel transplantation under oral immunosuppression: experimental study in
      the pig.

PMID- 9142286
TI  - Tacrolimus and mycophenolate mofetil in pig small bowel transplantation:
      different protocols and their outcome.

PMID- 9142288
TI  - Small bowel transplant combined with a reduced auxiliary liver graft.

PMID- 9142287
TI  - Transplantation of small bowel alone or with the liver in pigs: use of peripheral
      blood lymphocytes in monitoring rejection.

PMID- 9142289
TI  - Influence of different protocols of antibiotic prophylaxis on endoluminal
      bacterial overgrowth and translocation following small-bowel or combined liver
      small-bowel transplantation in a large-animal model.

PMID- 9142290
TI  - Genetic control of host-vs-graft reactivity after small bowel transplantation
      with heterotopic and orthotopic placement.

PMID- 9142291
TI  - Serotonin (5-HT): an enteroendocrine marker of rejection after small bowel
      allotransplantation in the pig.

PMID- 9142292
TI  - Serotonin (5-HT): an enteroendocrine marker of reperfusion injury after liver
      small bowel allotransplantation in the pig.

PMID- 9142293
TI  - Intestinal damage evaluation in swine allograft small bowel through hyaluronic
      acid quantification.

PMID- 9142294
TI  - An easy high-performance liquid chromatography quantification of monosaccharides
      from ileal mucosal tissue glycoproteins in pigs.

PMID- 9142295
TI  - Combined orthotopic liver-small bowel transplantation or small bowel
      transplantation in pigs: relations between survival, rejection, and mucosal
      morphometry.

PMID- 9142296
TI  - Altered pacemaker frequency gradient of a human small bowel allograft.

PMID- 9142297
TI  - Dopexamine and microcirculatory flow in transplanted small bowel: the Leeds
      experience.

PMID- 9142298
TI  - Alternative techniques for arterialization in multivisceral grafting.

PMID- 9142299
TI  - Living-related small bowel transplantation in adults: a report of two patients.

PMID- 9142301
TI  - Enteral feeding after intestinal transplantation: the Birmingham experience.

PMID- 9142300
TI  - The use of clonidine for the treatment of high intestinal output following small
      bowel transplantation.

PMID- 9142302
TI  - Pharmacokinetics of FK506 and mycophenolic acid in experimental and clinical
      intestinal transplantation.

PMID- 9142303
TI  - Early pharmacokinetic profiles of enteral tacrolimus after multivisceral
      transplantation.

PMID- 9142304
TI  - Intestinal adaptation in short bowel syndrome.

PMID- 9142305
TI  - 100 PT/YR pediatric home parenteral nutrition experience.

PMID- 9142306
TI  - Glucose-galactose malabsorption: is it an indication to bowel transplantation in
      childhood?

PMID- 9142307
TI  - Intestinal microvillous atrophy and transient neuronal dysplasia.

PMID- 9142308
TI  - Complications during home parenteral nutrition in children affected by congenital
      microvillous atrophy.

PMID- 9142309
TI  - Clinical heterogeneity of chronic intestinal pseudo-obstruction.

PMID- 9142310
TI  - The plasminogen-plasmin fibrinolytic system accelerates degradation of alginate
      poly-L-lysine-alginate microcapsules in vitro.

PMID- 9142311
TI  - Value of circulating immune parameters in renal transplantation.

PMID- 9142312
TI  - Effects of cyclosporine A on the regenerating endothelium following direct
      arterial injury.

PMID- 9142313
TI  - Preferential production of IgG2 antibodies by parenchymal lung B-lymphocytes
      during lung allograft rejection.

PMID- 9142314
TI  - Parental consent for pediatric cadaveric organ donation.

PMID- 9142316
TI  - CD4-targeted therapy induces "infectious" tolerance to cardiac allografts in
      sensitized rat recipients.

PMID- 9142315
TI  - Autologous lymphokine-activated killer cell therapy of lymphoproliferative
      disorders arising in organ transplant recipients.

PMID- 9142317
TI  - Transforming growth factor B1 decreases uptake of glutathione precursor amino
      acids in bovine pulmonary artery endothelial cells.
AB  - We have previously observed that transforming growth factor beta 1 (TGF beta 1)
      produces a pro-oxidant effect and decreases cellular glutathione (GSH) levels of
      cultured bovine pulmonary artery endothelial cells (BPAEC) (White A. C., S. K.
      Das, and B. L. Fanburg. Am. J. Respir. Cell Mol. Biol. 6:364-368, 1992). In the
      present studies we demonstrate that 2 ng/ml TGF beta 1 reduces the uptake of two
      GSH precursor amino acids (cystine and glutamate) by 50% (cystine; control 359.35
      +/- 100, TGF beta 1 187.7 +/- 26 pmol/10 min/10(6) cells, p < 0.05; glutamate;
      control 215.15 +/- 18, TGF beta 1 110.2 +/- 16 pmol/10 min/10(6) cells, p <
      0.001). The inhibitory effect of TGF beta 1 on the uptake of GSH precursor amino
      acids persisted in the presence of buthionine sulfoximine (inhibits gamma
      glutamyl cysteine synthetase, the rate limiting step in GSH synthesis) or
      acivicin (inhibits gamma-glutamyl transpeptidase). The uptake of leucine, an
      amino acid that does not serve as a precursor for GSH, was unaffected by TGF beta
      1. In additional experiments TGF beta 1 decreased the levels of cellular and
      medium GSH-indicating that TGF beta 1 did not increase efflux of GSH from BPAEC.
      We propose from these observations that TGF beta 1 decreases cellular
      glutathione, at least in part, through down regulation of precursor amino acid
      transport and, thereby, its rate of synthesis.

PMID- 9142318
TI  - 17 beta-Estradiol increases intracellular free calcium concentrations of human
      vascular endothelial cells and modulates its responses to acetylcholine.
AB  - In this study, we have investigated the effect of 17 beta-estradiol (E2) on
      intracellular free calcium concentrations ([Ca2+]i) in human umbilical vein
      endothelial cells (HUVEC) using fura-2 fluorescence. E2 at concentrations of 1nM 
      1 microM was added subsequently to HUVEC cultures which were either deprived of
      estrogens or preincubated with E2 (100 nM) for 24 hours. In both groups of
      cultures, E2 stimulated significant increases in [Ca2+]i in a dose-dependent
      manner. The effects were more prominent in E2-deprived cells. Preincubation of
      cells with tamoxifen or the presence of it in the buffer during the experiments
      did not inhibit the response of the cells to E2. Experiments performed in Ca2+
      free/EGTA buffer yielded transient increases in [Ca2+]i suggesting release of
      Ca2+ from intracellular stores was responsible for the initial peak, while
      sustained elevations were supported by Ca2+ influx from the extracellular space.
      Addition of La3+ abolished the sustained [Ca2+]i elevations. Carbachol (CCh)
      (1nM, 100 nM) did not induce changes in [Ca2+]i of estrogen-deprived cells but
      produced significant increases in [Ca2+]i of the same cells after incubation with
      E2 for 30 minutes. The cultures which were preincubated with E2 for 24 hours
      responded to carbachol directly. The results of our study indicate that E2 may
      modulate the functions of endothelial cells after only a brief exposure and also
      may be necessary for the response to acetylcholine especially at low
      concentrations.

PMID- 9142319
TI  - Optimization of transfection of human endothelial cells.
AB  - Recently developed transfection methods for mammalian cells provide a powerful
      means for the study of gene function. Unfortunately, human endothelial cells were
      relative refractory to the classic transfection techniques. In this study we
      compared the usability of calcium phosphate, DEAE-dextran transfection,
      transferrinfection, lipofection, and electroporation for the transfection of
      early passage HUVECs and for the human endothelial cell lines ECV 304 and EA.hy
      926. The classic transfection methods resulted in no or only marginal expression
      of the reporter gene E. coli beta-galactosidase. For lipofection experiments we
      compared the commercially available liposome formulations DOTAP and Transfectam
      with liposomes prepared of dimethyldioctadecylammoniumbromide (DDAB) or 1,2
      dimyristyloxypropyl-3-dimethylhydroxyethyl ammonium bromide (DMRIE) as the
      cationic lipid compound and dioleylphosphatidylethanolamine (DOPE) or Azolectin
      (a crude fraction of soybean lipids, commercially available as
      phosphatidylcholine II) as neutral co-lipid. Because the protocol for the
      chemical synthesis of DMRIE has not been published yet, we developed a protocol
      for the chemical synthesis of this cationic lipid. With transfection protocols
      optimized for each cell line, we could achieve transfection efficiencies up to
      2%. Compared to the other methods used, the lipofection proved to be a reliable
      technique for the efficient transfection of the human endothelial cell lines ECV
      304 and EA.hy 926. Although we achieved a maximum transfection efficiency of
      0.45% for the lipofection of HUVEC, the electroporation seemed to be the better
      choice for these cells.

PMID- 9142320
TI  - HPE cells: a clonal endothelial cell line established from human parathyroid
      tissue (human parathyroid cell line).
AB  - We report the culture and cloning of human endothelial cells derived from
      parathyroid tissue surgically removed from a patient affected by Multiple
      Endocrine Neoplasia Type 1 syndrome. These cells, known as HPE, have been
      isolated and maintained in culture by serial passages for more than 15 months.
      The clonal cell line grows in a medium containing serum substitutes which favour
      endothelial cell growth. HPE cells replicate with a mean doubling time of 120 h,
      showing typical functional and morphological features of endothelial cells, such
      as uptake of acetylated low density lipoprotein and positive reaction for Factor
      VIII-Related Antigen. Basic fibroblast growth factor, vascular endothelial growth
      factor, insulin-like growth factor type I and ascorbic acid stimulate cell
      proliferation, whereas transforming growth factor beta and heparin act as
      inhibitory factors. Prostaglandin E2, secretin and epinephrine increased cAMP
      production, while human parathyroid hormone, histamine and glucagon were inert.
      Cells were found to express pro-collagen alpha 1 (type I) mRNA. In HPE cells
      Restriction Fragments Length Polymorphism and PCR analysis did not show allelic
      loss at chromosome 11q12-13, known to be a typical feature of MEN 1 parathyroid
      tumors. These cells are the first example of an established normal human clonal
      cell line with an endothelial phenotype.

PMID- 9142321
TI  - Gem, a GTP-binding protein from mitogen-stimulated T cells, is induced in
      endothelial cells upon activation by inflammatory cytokines.
AB  - Using differential screening of cytokine-activated versus resting porcine aortic
      endothelial cells (PAEC), we have isolated a member of the family of Ras/GTP
      binding proteins. The cDNA encodes a 34-kilodalton protein showing 97% homology
      to Gem, a gene recently isolated from activated T cells, likely representing its
      porcine homologue. The amino acid sequence differs from the Ras consensus by the
      absence of a C-terminal isoprenylation site and a glycine to glutamic acid
      substitution in the third GTP-binding domain. We report here, that pigGem mRNA is
      strongly inducible in PAEC upon activation by either IL-1 alpha, TNF alpha or
      lipopolysaccharide (LPS). Low constitutive expression is found in several organs.
      Epitope-tagged pigGem transfected into endothelial cells (EC) localizes to the
      cytoplasm and to the inner side of the plasma membrane. Structural features of
      Gem and its inducibility apparently restricted to T cells and endothelial cells,
      together with Rad, a GTPase overexpressed in skeletal muscle cells of type II
      diabetic individuals, define a new branch within the superfamily of GTP-binding
      proteins.

PMID- 9142322
TI  - Sex-related differences in the response of spontaneously hypertensive rats to
      angiotensin-converting enzyme inhibitor.
AB  - We have compared the endothelium-dependent responses of thoracic aortic rings
      obtained from age-matched male and female SHR in order to explore gender
      differences in the effectiveness of antihypertensive drug therapy in correcting
      the endothelial dysfunction found in these animals. For this, concentration
      effect curves to acetylcholine and sodium nitroprusside were obtained using
      aortic rings with and without endothelium isolated from male and female rats
      which had or had not been pre-treated with enalapril for 72 h (acute) or 15 d
      (chronic). The maximal responses achieved and the EC50s were determined. The
      blood pressure of male and female spontaneously hypertensive rats (SHR) decreased
      to normal levels within 72 h of initiating treatment with enalapril and remained
      normal during the remainder of the treatment period (15 d). However, enalapril
      was not effective in restoring a normal blood pressure in all of the male and
      female SHR. Female SHR were more responsive to enalapril after both acute and
      chronic treatment (70% of the females and 45% of the males became normotensive).
      Enalapril corrected the decreased response to acetylcholine in male but not in
      female SHR. An increased sensitivity to sodium nitroprusside, an endothelium
      independent vasodilator, was observed after acute or chronic treatment with
      enalapril in aortic rings with endothelium from male SHR. Indomethacin restored
      the decreased response to acetylcholine in aortic rings from enalapril-treated
      females and potentiated the response to acetylcholine in aortic rings from
      treated male SHR. We conclude that: a) there are significant differences in the
      responses of male and female SHR to enalapril, b) the imbalance in endothelium
      dependent relaxing and contracting factors in SHR is corrected by enalapril in
      male but not in female SHR, c) correction of the endothelial dysfunction probably
      occurs independently of the normalization of blood pressure levels and appears to
      be gender-dependent.

PMID- 9142323
TI  - Vascular origin determines angiotensin I-converting enzyme expression in
      endothelial cells.
AB  - Previous observations on the heterogeneous distribution of von Willebrand factor
      in the vascular endothelium led us to examine the expression of angiotensin I
      converting enzyme (ACE) in function of the vascular origin of endothelial cells
      (EC). EC from pig thoracic aorta, pulmonary artery, inferior vena cava and brain
      capillaries were cultured and assayed for ACE by enzymatic radiochemical
      determination and by western-blot and immunofluorescence using an antiACE
      polyclonal antibody. EC from the various vascular levels secreted ACE in the
      culture medium; western-blot analysis showed its presence at cellular level and
      immunofluorescence confirmed its location on the plasma membrane. But
      quantification revealed that EC from pulmonary artery contain more ACE than EC
      from the other vessels, especially from brain capillaries; immunofluorescence
      correlated well with the functional data. In contrast, secretion of ACE by brain
      capillaries EC was faster than that of arteries and of vena cava, the latter
      being the less effective. This differential ACE expression along the vascular
      tree could have a pharmacological implication since ACE inhibitors, used in the
      treatment of arterial hypertension, may act more at the vascular level than on
      the plasma renin-angiotensin system. On the other hand, endothelial distribution
      of ACE was different from that of von Willebrand factor; in particular we showed
      that EC cultured from vessels of pigs homozygous for the von Willebrand disease,
      in which von Willebrand factor synthesis was completely abolished, normally
      express ACE.

PMID- 9142324
TI  - Proceedings of the 3rd International Symposium on Bone Marrow Transplantation in
      Thalassemia. Pesaro, Italy, 28-29 September 1996.

PMID- 9142325
TI  - 23rd Annual meeting of the European Group for Blood and Marrow Transplantation
      and 13th meeting of the Nurses Group. Aix-les-Bains, France, March 23-27, 1997.
      Abstracts.

PMID- 9142326
TI  - [French Language Association for the Study of Diabetes and Metabolic Diseases.
      Amiens, France, 19-23 March 1997. Abstracts].

PMID- 9142327
TI  - The Physiological Society of Japan 73rd annual meeting. Fukui, April 3-5, 1996.
      Abstracts.

PMID- 9142329
TI  - Society of General Internal Medicine 20th annual meeting. Washington, D.C., May 1
      3, 1997. Abstracts.

PMID- 9142328
TI  - [Proceedings of the 1st-5th meetings of the Japanese Society of
      Echocardiography].

PMID- 9142330
TI  - North American Society of Pacing and Electrophysiology 18th annual scientific
      sessions. New Orleans, Louisiana, May 7-10, 1997. Abstracts.

PMID- 9142331
TI  - [The 70th annual meeting of the Japan Society for Occupational Health. Toyama,
      Japan. April 9-11, 1997. Abstracts].

PMID- 9142332
TI  - E-cadherin transforms embryonic corneal fibroblasts to stratified epithelium with
      desmosomes.
AB  - Important and precisely regulated transitions in tissue phenotype from epithelium
      to mesenchyme and from mesenchyme to epithelium occur in the developing embryo.
      The gene for E-cadherin has been shown to cause fibroblastic cell lines to become
      epithelioid in culture. We asked whether or not the activities of the E-cadherin
      gene could cause a definitive embryonic mesenchyme to transdifferentiate into an
      epithelial phenotype. Primary corneal fibroblasts from 6- to 7-day-old chick
      embryos were contransfected by impact loading with plasmids containing E-cadherin
      and Neo genes and selected in G418. The fibroblasts expressing E-cadherin
      aggregate, localize E-cadherin to lateral surfaces, and form stratified epithelia
      that develop zonulae occludentes and adherentes, connexin 43, cytokeratin,
      desmoplakin, and desmosomes. Vimentin intermediate filaments persist and no
      basement membranes appear, even though the cells synthesize laminin and type IV
      collagen. Our study is the first to demonstrate the ability of E-cadherin to
      induce fibroblasts to form desmosomes and stratified epithelia. The primary
      embryonic fibroblasts apparently have more developmental potential to
      transdifferentiate into epithelia than do the fibroblastic cell lines previously
      studied. We conclude that E-cadherin is likely to play an important role in
      transformation of mesenchyme to epithelium in the embryo.

PMID- 9142333
TI  - Migration of enteric neural crest cells in relation to growth of the gut in avian
      embryos.
AB  - Neural crest cell migration in the gut and the growth of the mid- and hindgut of
      avian embryos was investigated by a combination of whole-mount immunofluorescence
      of the HNK-1 neural crest marker epitope, chorioallantoic membrane grafting and
      morphometry. HNK-1-labelled cells advanced rostrocaudally in the gut of quail
      embryos (to the duodenum by stage HH 21, to the umbilicus by HH 25, to the ceca
      by HH 27, to the cloaca by HH 33). The timetable in chick embryos appeared to be
      slightly slower, but neural cells were obscured by background fluorescence in
      this species. More rostral regions of the gut commenced rapid growth earlier than
      more caudal regions (preumbilical small intestine after HH 26, postumbilical
      small intestine after HH 27 and colorectum after HH 28), and the small intestine
      and ceca grew most rapidly in length while the colorectum grew most rapidly in
      diameter. The rates of growth of the gut were low prior to the stage when HNK-1
      labelled cells normally arrive in the small intestine, ceca and rostral
      colorectum, but increased dramatically after arrival. In the caudal colorectum
      rapid growth had commenced at the time of arrival of these cells. These data are
      consistent with the idea that a delay in arrival of vagal neural crest cells at
      any point in the intestine could jeopardize the ability of the cells to fully
      populate the remainder of the gut, due to the normal growth spurt causing the
      migration end-point to recede faster than the rate of neural crest cell
      migration. Thus, a mismatch in timing of neural crest cell migration and gut
      growth could play a role in the etiology of some forms of Hirschsprung's disease.

PMID- 9142334
TI  - Three-dimensional imaging of rhodamine 123 fluorescence distribution in human
      melanoma cells by means of confocal laser scanning microscopy.
AB  - Three-dimensional (3D) imaging of intracellular rhodamine 123 fluorescence
      distribution was performed by means of confocal laser scanning microscopy (CLSM).
      Human IGR melanoma cells grown in monolayer or multicellular spheroid culture
      were studied for elucidating mitochondrial membrane potential characteristics,
      and cell and nucleus volume dimensions. Microspheres 6 microns in diameter loaded
      with rhodamine B were used to calibrate our instruments for performing 3D imaging
      of optical sections as obtained by CLSM. Accurate optical slicing is only
      possible taking into consideration the physical characteristics of the objectives
      used like chromatic and spherical aberrations, depth discrimination or cover slip
      correction and the temperature dependence of the immersion medium. While 3D
      imaging of optical slices can be carried out showing the original shape of the
      object being tested without physical distortion, 3D images of microspheres show
      well-reproducible structures of rhodamine B fluorescence. These can be explained
      by a superposition of two effects, namely scattering of the fluorescence light
      and a gradient of the electromagnetic field strength of the laser beam due to the
      shape of the object. 3D imaging of optical slices of IGR cells in monolayer or
      multicellular spheroid culture, which have been loaded with rhodamine 123, show
      the location of the dye predominantly within the cytoplasm of the cells with a
      remarkable heterogeneity of fluorescence intensity within and between single
      cells, indicating differences in the mitochondrial membrane potential and thus in
      the metabolic activity. Due to the heterogeneity of the cell shape the cell
      nucleus occupies between 4 and 14% of the total cell volume. These data reveal
      calibrated 3D imaging as a valuable noninvasive tool to visualize the
      heterogeneity of cell parameters under different cell culture conditions.

PMID- 9142335
TI  - Immunoelectron microscopy of corticotropes and melanotropes in the pituitary
      gland of the European ferret, Mustela putorius furo.
AB  - The superimposition technique and protein A-gold method of immunoelectron
      microscopy were employed to study the ultrastructure of corticotropes as well as
      melanotropes in the ferret pituitary gland. This is the first study ever
      elucidating the ultrastructural heterogeneity of melanotropes in mammalian pars
      intermedia on an immunocytochemical basis. Morphological heterogeneity of pars
      distalis corticotropes has also been elucidated. It is suggested that the
      different subtypes may represent stages of development (histogenesis), or
      functional phases of a single cell type. In addition, the occurrence and
      distribution of both corticotropes and melanotropes in different hypophyseal
      components have been studied by light-microscopic immunocytochemistry.

PMID- 9142336
TI  - Mast cells in the laryngeal mucosa of the rat. Effect of compound 48/80 and
      dexamethasone: a quantitative and immunohistochemical study at the light- and
      electron-microscopic levels.
AB  - Mucosal mast cells (MMCs) and connective tissue mast cells (CTMCs) in the
      epiglottic and subglottic regions in the rat larynx were characterized and
      quantified by immunohistochemistry and by light and electron microscopy, in
      control rats and rats injected intraperitoneally with dexamethasone and compound
      48/80. Considerable regional differences were observed in the distribution of
      mast cells, especially in the epiglottis, where most cells were located on the
      laryngeal side. In the epithelium of the subglottic region the MMCs showed
      immunoreactivity for 5-hydroxytryptamine, in contrast to the epithelial MMCs in
      the epiglottis. In ultrathin sections, the subglottic MMCs contained larger but
      fewer granules compared with the epiglottic MMCs. After treatment with
      dexamethasone, the MMCs in the epithelium disappeared, while after treatment with
      compound 48/80 a large number of the CTMCs in the lamina propria became
      degranulated, though still present. This study shows that MMCs in the epiglottic
      and subglottic regions may be of two subtypes, differing in number and size of
      the granules as well as in chemical content.

PMID- 9142337
TI  - Differential cell replication within the periosteum of the pig mandibular ramus.
AB  - The periosteum is anatomically and functionally divided into two layers. The
      inner osteoblastic layer contributes to local appositional bone growth. The outer
      fibroblastic layer receives the attachments of muscles and responds to bone
      growth by a more global enlargement. Coordinated growth of the layers could
      theoretically be produced by parallel replication rates in the layers followed by
      migration of fibroblastic layer cells. Alternatively, replication rates in the
      layers could differ, those in the osteoblastic layer reflecting local apposition
      and those in the fibroblastic layer responding to total bone growth. To test
      these alternatives, we compared two regions of the pig mandible, one appositional
      and one resorptive, equidistant from the major growth sites of the bone. Four 2
      week-old pigs were injected i.p. with 5-bromo-2'-deoxyuridine (BrdU) to label
      replicating cells. Three hours subsequent to BrdU injection, animals were
      sacrificed. The mandibles were sectioned and processed immunocytochemically for
      BrdU. Periosteal cell mitotic activity was analyzed selectively at the level of
      the mandibular foramen on the medial and lateral ramal surfaces. The proportion
      of labeled cells was determined by grid-point analysis. Individual differences
      were minor but regional differences were striking. As expected, the osteoblastic
      layer of the lateral surface exhibited a greater proportion of mitotic cells than
      did the medial surface (p = 0.037). However, no such difference was seen in the
      fibroblastic layer, where medial and lateral sides exhibited identical
      replication activity. These results strongly support the second alternative, that
      cell division is differentially controlled in the two periosteal layers.

PMID- 9142338
TI  - The valva portalis renalis in the duck (Anas platyrhynchos).
AB  - The morphology of the valva portalis renalis of the duck was investigated, using
      histological, SEM and TEM techniques. The wall thickness of the vena iliaca
      externa, the vena portalis renalis caudalis, the vena iliaca communis and the
      vena renalis caudalis was morphometrically evaluated. The blood pressure in these
      veins was measured using a three-way H2O manometer. The valva portalis renalis
      was composed primarily of epithelioid cells and lined with endothelium.
      Throughout the entire valva there was a dense complex of nerve structures made up
      of fibers and fiber bundles which also extended beneath the endothelium of the
      valva and around the subendothelial epithelioid cells. The wall thicknesses of
      the veins supplying the renal portal system (vena iliaca externa and vena
      portalis renalis caudalis) were greater than those of the vessels collecting the
      renal refluent venous blood (vena iliaca communis and vena renalis caudalis). In
      addition, the blood pressure values taken in the vena iliaca externa and the vena
      portalis renalis caudalis were much higher than those in the vena iliaca communis
      and the vena renalis caudalis. The above observations suggest that the renal
      portal system works at higher blood pressure levels than the general venous
      system and that the valva portalis renalis regulates its aperture in order to
      maintain a constant blood pressure and a continuous blood flow in the renal
      portal system vessels, hence avoiding damage to the renal parenchyma caused by
      pressure overloads.

PMID- 9142339
TI  - Circular arterial supply of the pisiform bone.
AB  - The arterial vascularization of the pisiform bone was studied from 15 cadavers to
      assess the possibility of pedicled pisiform transfer in Kienbock's disease. The
      arterial vascularization of the pisiform bone comes from three pedicles: an upper
      pedicle arising from the dorsal carpal artery, a lateral pedicle arising from the
      ulnar artery, and a lower pedicle arising from the deep palmar branch of the
      ulnar artery. The pisiform bone is well vascularized and, whatever the
      distribution of the pedicles within the bone itself, we always found an arterial
      circle around it. The lengths of the upper and lower pedicles expressed as ratios
      of the length or width of the pisiform bone were variable, as indicated by the
      coefficient of variation that was greater than 36%. There was no significant
      correlation between the length of the upper or lower pedicle and the length or
      width of the pisiform bone. The length of the upper pedicle, which was greater
      than the distance between the origin of the dorsal carpal artery and the center
      of the lunate, allows a pedicled pisiform transfer in Kienbock's disease.
      Nevertheless, it is difficult to assert definitively that the upper pedicle is
      sufficient to avoid a partial necrosis of the pedicled pisiform bone.

PMID- 9142340
TI  - Duplicated hepatic artery: radiologic and surgical implications.
AB  - Preoperative angiography of the coeliac trunk and superior mesenteric artery is
      routinely performed before liver resections and transplantations. For this
      purpose, it is usual to inject each branch of the coeliac trunk separately.
      Selective angiographic studies, however, may lead to overlooking surgically
      essential anatomic variations of the hepatic blood supply, as demonstrated by the
      present report. A case of a duplicated hepatic artery is presented, its
      radiologic and surgical implications discussed, and the relevant literature
      reviewed. This uncommon and particularly evocative feature illustrates the
      clinical importance of a sound knowledge of anatomical variants.

PMID- 9142341
TI  - A 55-kDa endonuclease of mammalian mitochondria: comparison of its subcellular
      localization and endonucleolytic properties with those of endonuclease G.
AB  - A novel endonuclease of 55-kDa was found in rat liver mitochondria by a
      zymographic assay, in addition to the 29 kDa enzyme that is well-known as
      endonuclease G (Endo G). Subcellular localization of these enzymes in rat liver
      cells was examined by biochemical fractionation. Endo G was located in both
      nuclei and mitochondria as has been previously reported, while the 55-kDa enzyme
      was only detected in the mitochondrial fraction. The levels of the endonucleases
      in the mitochondria varied greatly among the rat organs, and the activity in the
      heart was about 30 times higher than that in the liver. The 55-kDa enzyme and
      Endo G were extracted from bovine heart mitochondria with 0.4 M NaCl. During
      purification the 55-kDa enzyme and Endo G were copurified because of their
      similar chromatographic behavior, so they were separated by gel filtration or
      electrophoresis in the presence of SDS and the proteins were then renatured. The
      nucleolytic properties of the 55-kDa enzyme resembled those of Endo G and other
      known mitochondrial nucleases. The enzyme degraded single-stranded DNA more
      rapidly than duplex DNA at a weak alkaline pH1 requiring Mg2+ or Mn2+ but not
      Ca2+ or Zn2+. Nicks generated by the enzyme had 5'-P and 3'-OH ends. The 55-kDa
      enzyme, like Endo G, displayed an unusually strong preference to nick within a
      (dG)n.(dC)n tract.

PMID- 9142343
TI  - Intrathecal oxygen concentration as a new indicator of spinal cord ischemia.
AB  - A number of approaches have been put forward to monitor spinal cord ischemia
      during thoracic and thoracoabdominal aortic occlusion. However, none of these can
      ultimately prevent devastating complications which result from ischemic spinal
      cord injury. A direct measurement of the oxygen content of the spinal cord may
      accurately indicate the perfusion state, but in practice it is impractical. We
      surmised that intrathecal and/ or epidural oxygen concentration(I-pO2 and E-pO2,
      respectively) accurately reflect oxygen content in the spinal cord. So, we
      examined whether or not I-pO2 and/or E-pO2 correlated with the spinal cord pO2 (S
      pO2) in dogs. In nine mongrel dogs, a model of graded spinal cord ischemia was
      developed by stepwise alternation of the level of aortic occlusion with an
      intraaortic balloon catheter. I-pO2, E-pO2 and S-pO2 were measured with a mass
      spectrometer. Our results show that, both I-pO2 and E-pO2 significantly
      correlated with S-pO2. I-pO2 correlated with S-pO2 better than E-pO2 did.
      Therefore, I-pO2 can be used as a new indicator for spinal cord ischemia, and I
      pO2 monitoring would be useful to prevent paraplegia associated with thoracic
      aortic surgery.

PMID- 9142342
TI  - Histopathology and clinical results of carpal tunnel syndrome in idiopathic cases
      and hemodialysis patients.
AB  - The results of the histological examinations of specimens of the tenosynovium of
      the flexor tendon, the epineurium and the transverse carpal ligament from two
      groups of Japanese patients with carpal tunnel syndrome (idiopathic and
      hemodialysis) were compared. Amyloid deposits, positively identified as beta 2
      microglobulin, appeared in all patients in the long-term hemodialysis group, but
      in no patients in the idiopathic group. Although the pathogenesis differed
      between the two groups, both resulted in nerve compression in the carpal tunnel.
      Therefore, surgical release is considered beneficial for both groups.

PMID- 9142344
TI  - Increased serum levels of the carrier molecules of the carbohydrate antigen
      sialyl Lewis X in liver diseases.
AB  - The serum levels of the carbohydrate antigen sialyl Lewis X (SLEX) increase in
      liver diseases (Sunayama T, Okada Y, Tsuji T., J Hepatol 1994; 19: 451-458).
      However, it is not known whether the increased serum SLEX levels are associated
      with the increased levels of its carrier molecules and/or the increased density
      of SLEX per carrier molecule. By using of rabbit antibody against an SLEX
      positive fraction from HepG2 culture supernatant, we developed an enzyme-linked
      immunosorbent assay to determine the serum levels of the carrier molecules of
      SLEX (CMSLEX). The CMSLEX-levels in patients with hepatocellular carcinoma were
      significantly higher than those of normal controls (P < 0.001) and benign chronic
      liver diseases, i.e., chronic active hepatitis, mild and severe form, and liver
      cirrhosis (P < 0.05). Patients with chronic persistent hepatitis and chronic
      active hepatitis, mild form, had higher CMSLEX-levels than normal controls (P <
      0.05). The serum CMSLEX-levels did not differ significantly among benign liver
      diseases. We concluded that serum CMSLEX-levels increase nonspecifically in liver
      diseases. This is a possible molecular mechanism for the increased serum SLEX
      levels in liver diseases.

PMID- 9142345
TI  - A clinical analysis of malignant schwannoma.
AB  - In this study, we reviewed the clinical features of 11 patients with malignant
      schwannoma who were treated in our institute. Five patients had coexistent von
      Recklinghausen's disease and one of them showed multifocal occurrence. Patients
      with the centrally located tumors had a poorer prognosis than those with the
      others. The overall 3-year survival rate was 36%; 40% in patients with von
      Recklinghausen's disease and 33% in the others. At the time of the last follow
      up, 9 patients had died of the tumor, one continued to be tumor free, and one was
      alive with tumor. Postoperative local recurrence developed in 5 patients (45%); 4
      out of 6 patients (67%) who underwent a marginal excision and one out of 3 (33%)
      who underwent primary amputation. There was no local recurrence in patients after
      a wide excision with at least 3 cm of normal tissue removed surrounding the tumor
      in all directions. Nine patients (82%) developed pulmonary metastasis. The effect
      of adjuvant chemotherapy was not clear in this study. The high risk of pulmonary
      metastasis in this disease indicates the necessity of more effective adjuvant
      chemotherapy.

PMID- 9142346
TI  - Preoperative multidisciplinary treatment with hyperthermia for soft tissue
      sarcoma.
AB  - We report the results of phase I/II studies of preoperative multidisciplinary
      treatment of 14 patients with soft tissue sarcoma using hyperthermia from
      November 1990 to April 1995. The preoperative treatment was conducted with thermo
      radio-chemotherapy in 11 cases of stage III, and with thermo-radiotherapy as well
      as thermo-chemotherapy in three cases of stages I and II. Hyperthermia was
      carried out twice a week with totals ranging from 4 to 14 times (average: 8.4
      times); each session lasted 60 min. Radiotherapy was administered four or five
      times per week, and the dose was 1.8 2Gy/fraction, with a total of 30-40 Gy in a
      four week period. Chemotherapy was mainly in the form of MAID regimen (2
      mercaptoethanesulphonic acid (mesna), adriamycin, ifosfamide and dacarbazine).
      The tumors were surgically resected in all patients after completing the
      preoperative treatment. The efficacy rate, as expressed by the percentage of
      either tumors in which reduction rate was 50% or more, or tumors for which post
      treatment contrast enhanced CT image revealed low density volumes occupying 50%
      or more of the total mass, was 71% (ten of the 14 tumors). The mean tumor
      necrosis rate in the resected specimens was 78%. The tumor necrosis rate was
      significantly high (P < 0.05) in patients whose Time > or = 42 degrees C was of
      long duration. Postoperative complications were observed in six patients; among
      these, two patients developed wound infection that required surgical treatment as
      a complication of surgery performed in the early stage following the preoperative
      treatment. After a mean postoperative follow-up of 27 months, distant metastasis
      occurred in four patients resulting in three fatalities. The three-year
      cumulative survival rate was 64.3%. No local recurrence was observed in any
      patient during the follow-up, thus confirming our hypothesis that preoperative
      multidisciplinary treatment has an excellent local efficacy. We think that it
      would be valuable to conduct, at many facilities, phase III studies on the
      treatment of soft tissue sarcoma by a combination of surgery and preoperative
      multidisciplinary treatment using hyperthermia, paying close attention to the
      interval between these two modalities.

PMID- 9142347
TI  - New evaluation method for postoperative scar redness.
AB  - Even after successful operations, ugly postoperative skin scars are often
      distressing to patients and their parents. To judge the success of surgical
      methods and postoperative treatment, postoperative scars should be evaluated
      using a quantitative system. Height and width are easily measured, but scar
      redness is not. We have developed a simple and effective method for evaluating
      scar redness. According to the color definitions employed in computer graphics,
      each color can be expressed as RGB (red, green or blue) coordinates (r, g, b): 0
      < or = r, g, b < or = 10. The degree of scar redness is defined by the following
      formula: redness score (RS) = (r1 - r0)2 + (g1 - g0)2 + (b1 - b0)2. Here, (r1,
      g1, b1) = coordinates of the scar color and (r0, g0, b0) = coordinates of the
      surrounding skin color. RS was evaluated in 59 children (35 males, 24 females;
      ages 1 month to 12 years old) who had scar redness after congenital cardiac
      surgery. For each patient, scar color and surrounding skin color was identified
      on the color sample table. Scar redness was also evaluated by the conventional
      grading method: 1 = mild, 2 = moderate and 3 = severe. The RS of the colored
      scars ranged from 4 to 100 (38 +/- 27). By the conventional grading method, 44
      scars were grade 1, 15 grade 2 and none grade 3. RS was significantly higher
      among grade 2 than grade 1 patients, 52 +/- 25 and 33 +/- 27, respectively (P <
      0.05). Given its subjectivity, the conventional grading method yields variable
      data surrounding skin color, moreover, is not considered. Our new evaluation
      method using RS effectively and accurately defines scar and skin colors, and
      allows quantitative studies of these factors.

PMID- 9142348
TI  - Endoscopic carpal tunnel pressure measurement: a reliable technique for complete
      release.
AB  - Carpal tunnel syndrome is diagnosed by clinical symptoms, Tinel's sign, Phalen's
      test and electromyography. Carpal tunnel pressure measurement can also aid in the
      precise identification of excessive pressure sites that indicate locations for
      release. In this study, pressure measurements made during endoscopic carpal
      tunnel release at 5 points were significantly higher anywhere in the carpal
      tunnel than outside the tunnel and decreased markedly after release. We concluded
      that our measurement technique can improve the reliability of endoscopic carpal
      tunnel release by decreasing the likelihood of missing any nerve entrapment
      sites.

PMID- 9142349
TI  - Cerebral blood flow velocity in handicapped children.
AB  - Using a transcranial Doppler blood flowmeter, the blood flow velocity (BFV) ratio
      of the middle cerebral artery (MCA) to the basilar artery (BA) was investigated
      in 12 patients with severe motor and intellectual disability syndrome. The BFV of
      the MCA was also investigated in 58 handicapped children, classified according to
      the severity of their motor and intellectual disability. The ratio of the MCA to
      the BA was lower by 2 SD from the mean of our previously reported standard value
      in 8 out of the 12 cases with severe motor and intellectual disability syndrome,
      suggesting a more profound decrease in the level of brain activity in the MCA
      area than that of the BA area. The BFV of the MCA mainly decreased in cases
      belonging to the category of the most severe motor disability (bed-ridden).
      Hence, it is suggested that motor disability is the main factor related to the
      decrease in the BFV of the MCA.

PMID- 9142350
TI  - Families of adults with severe mental illness--the next generation of research:
      introduction.

PMID- 9142351
TI  - Effectiveness of two models of brief family education: retention of gains by
      family members of adults with serious mental illness.
AB  - The retention of benefits from two models of family education was compared with
      maturational effects in an untreated control group. The three-month interventions
      showed an initial effect for self-efficacy regarding a mentally ill relative that
      did not significantly diminish during the following six months. However, no
      significant differences on this measure were found between the treated groups and
      the untreated controls. Ways of refining the interventions and measures so as to
      improve gains and retain them over time are discussed.

PMID- 9142352
TI  - Benefits of support groups for families of adults with severe mental illness.
AB  - Predictors of benefits derived from participating in support groups for families
      of persons with mental illness were examined. A survey of 131 families indicated
      that social support resources outside the group, as well as support received from
      and provided by the group, were associated with information acquired by the
      participant. Improved relationships with family and the ill relative were
      predicted by the participant's health and provision of support in the group.

PMID- 9142353
TI  - Perceived burden among caregivers of adults with serious mental illness:
      comparison of black, Hispanic, and white families.
AB  - Differences in perceived burden were investigated among black, Hispanic, and
      white groups of caregivers of adults with serious mental illness. Controlling for
      sociodemographic characteristics and caregiving-related stressors, black
      caregivers tended to report less burden than whites, a result not explained by
      protective mechanisms (social support, religious involvement, illness
      attributions). No statistically significant differences were found in perceived
      burden between Hispanic and white caregivers.

PMID- 9142354
TI  - The consumer recovery vision: will it alleviate family burden?
AB  - Research on families of people with severe mental illness has identified
      significant caregiving burden. Although professional interventions generally
      assume that families have a major role in the client's progress, the focus of the
      consumer movement on recovery through empowerment, peer supports, and consumer
      run services may have important, as yet unquantified, effects. Keeping in mind
      the functional heterogeneity of individuals with mental illness, it is suggested
      that consumer emphasis on autonomy may provide the major relief for family
      burden.

PMID- 9142355
TI  - Positive parent/adult child relationships: impact of severe mental illness and
      caregiving burden.
AB  - Comparison of 222 parents of an adult child who had a psychiatric disability and
      434 parents with a nondisabled adult child revealed that parents' positive
      appraisals of their relationship with the target child was significantly
      predicted by their perceived caregiving burden, but not by their child's
      psychiatric status. Implications for interventions that enhance parent/adult
      child relationships are discussed.

PMID- 9142356
TI  - Factors associated with subjective burden in siblings of adults with severe
      mental illness.
AB  - Experiences of subjective burden were analyzed in a sample of 164 siblings of
      persons with serious mental illness. Findings indicated that the well sibling's
      experience of burden was consistently related to the symptomatology of the ill
      sibling. In addition, those who viewed the ill sibling's behavior as outside his
      or control exhibited lower levels of subjective burden than did those who viewed
      the behavior as within the sibling's control. Implications for research and
      clinical intervention are discussed.

PMID- 9142357
TI  - The next generation of research: views of a sibling-psychiatrist-researcher.
AB  - A sibling of a person with severe mental illness who is also a psychiatrist and a
      researcher responds to the next generation of research proposed in the articles
      in this special section. Four issues are emphasized: benefit vs. burden;
      association, causation, and statistical modeling; strengths and limitations of
      study samples; and interventions.

PMID- 9142358
TI  - A consumer perspective on the family agenda.
AB  - The point of view of a mental health researcher who was diagnosed with bipolar
      disorder when her four children were young is applied to several of the other
      articles in this section. She comments on various aspects of work with families
      in which one member has a serious mental illness, raising and discussing issues
      relevant to consumers, as well as to family members.

PMID- 9142359
TI  - Families of adults with severe mental illness: new directions in research.
AB  - Challenges to the next generation of family researchers are enormous as they move
      beyond the more global concept of family and begin to address the great diversity
      among families with mentally ill relatives. Since most mental illnesses are
      chronic conditions, families must also be understood from the long-term
      perspective of the family life cycle.

PMID- 9142360
TI  - Intimate violence in the lives of homeless and poor housed women: prevalence and
      patterns in an ethnically diverse sample.
AB  - In a study of 436 homeless and poor housed mothers, nearly two-thirds reported
      severe physical violence by a childhood caretaker, 42% reported childhood sexual
      molestation, and 61% reported severe violence by a male partner. Comparisons of
      homeless and housed women are presented, and implications for prevention and
      intervention are discussed in light of recent welfare reform legislation.

PMID- 9142361
TI  - Exploring the social construction of bereavement: perceptions of adjustment and
      recovery in bereaved men.
AB  - The general public's view of bereavement in Israel was studied by means of a
      series of vignettes describing various reactions of a man at mid-life alternately
      to the death of an adult son and then to the death of a spouse. Respondents
      believed that the bereaved were particularly affected when the deceased was an
      adult child; functioning was impaired; and the relationship to the deceased was
      conflictual. A continuing relationship to the deceased was considered normative
      five years after death. Implications for theory and clinical practice are
      offered.

PMID- 9142363
TI  - Multicultural identity and gay men in the era of AIDS.
AB  - In establishing integrated identities, gay men face psychosocial challenges that
      differ from those of most heterosexuals, although heterosexual males of minority
      cultures may confront similar developmental tasks. In the 1990s, the need for gay
      men to integrate bicultural identity and the "coming-out" process is further
      complicated by the stigma of AIDS. This paper aims to enhance clinicians'
      understanding of the multiple influences of culture and subculture, the AIDS
      epidemic, and racial and ethnic factors on the healthy development of gay males.

PMID- 9142362
TI  - Foster care's youngest: a preliminary report.
AB  - The impact of welfare reform on foster care is examined in relation to children's
      mental health. Initial assessment of 125 young foster children randomly assigned
      to a special program found that half rated below normal on mental and psychomotor
      development, with two-thirds below normal on emotional regulation and motor
      quality. Implications for social policy and program planning, and the need for
      ongoing research, are discussed.

PMID- 9142364
TI  - Prodromal symptoms of recurrent major depressive episodes: a qualitative
      analysis.
AB  - In four focus groups, 16 people with major depressive or bipolar disorder were
      asked to describe the onset of an acute depressive episode. Findings indicate
      that those entering a major depressive episode often have difficulty identifying
      prodromal symptoms, although they experience early warning phases. These phases
      and described, and implications for clinical intervention are outlined.

PMID- 9142365
TI  - Risky sexual behavior among substance-abusing adolescents: psychosocial and
      contextual factors.
AB  - Of 120 substance-abusing adolescents and young adults undergoing treatment, the
      majority reported engaging in several types of risky sexual behavior, both with
      and without concurrent substance use. Data analysis revealed that AIDS knowledge,
      decision-making style, drinking motives, and perceived vulnerability to HIV were
      significant predictors of such behavior. Findings are discussed with a view to
      enhancing prevention efforts among high-risk adolescents.

PMID- 9142366
TI  - Parents of adults with mental retardation living in-home and out-of-home:
      caregiving burdens and gratifications.
AB  - Interviews with parents of adult children with mental retardation were conducted
      to identify differences in caregiver burdens and gratifications, based on in-home
      and out-of-home placement. Parental responses indicate that caretakers of adult
      children with mental retardation are worried and feel responsibility for their
      care regardless of residential placement of the adult child.

PMID- 9142367
TI  - Parental overprotection and its relation to perceived child vulnerability.
AB  - A study of 280 parents with a child age 5-10 years examined the relation between
      and correlates of parental overprotection (less education, younger child age,
      being an only child) and parental perception of increased child vulnerability
      (history of life-threatening illness, child medical condition, first child). One
      third of parents who considered their child vulnerable were also considered
      overprotective.

PMID- 9142368
TI  - An overview of the risk assessment of hazardous materials and the role of
      toxicology.
AB  - The chemical risk assessment process and the need for health-based approaches to
      identify and characterize potential hazardous substances will be discussed. The
      risk assessment process can be applied to both workplace and environmental
      settings. Toxicology will be defined and related to the risk assessment process.
      A brief overview of toxicity screens and tests will be presented in order to help
      make toxicity data more meaningful. Toxicity data for Halon 1301 replacements and
      trichloroethylene (TCE) will be presented as examples. The paper will conclude
      with a description of tri-service toxicology; what it is and what this laboratory
      provides to the Department of Defense (DOD), industry, and academia.

PMID- 9142369
TI  - The adequacy of capillary specimens for determining whole blood lead.
AB  - In response to demands for reliable alternatives to collection of venous
      specimens for determination of whole blood lead levels in children, the Centers
      for Disease Control has called for increased research into capillary
      methodologies. In this study, a three tiered approach was developed to assess the
      adequacy of capillary specimens for determining whole blood lead. Patient blood
      lead results from capillary and venous specimens were compared for obvious
      differences. Next, follow-up specimens for patients with elevated lead levels
      were compared with the initial results. In addition, experiments were conducted
      to determine whether or not handwashing eliminates gross contamination. Although
      the differences are not clinically important, the mean, 3.83 micrograms/dL for
      5,100 venous specimens, was significantly lower (p < 0.005) then the mean of 4.6
      micrograms/dL for 1,100 capillary specimens. Gross contamination was rare. Lead
      levels in follow-up specimens on patients whose initial screens were elevated
      were generally low. Handwashing greatly reduced the amount of external lead
      contamination. It is concluded that capillary specimens are an acceptable
      alternative to venous specimens for whole blood screening programs provided the
      patient and collector meticulously follow the prescribed collection protocol.
      Nevertheless, all elevated whole blood lead screening results, venous or
      capillary, should be confirmed with a venous collection before follow-up action
      is taken.

PMID- 9142370
TI  - Relationship between bilirubin, apolipoprotein B, and coronary artery disease.
AB  - Lipoprotein lipids and apo B from 254 male patients were compared with bilirubin
      as a risk factor for coronary artery disease (CAD). Patients were classified as:
      1, Normal, all vessels < 20% stenosis, n = 83; or 2, CAD, at least one vessel >
      70%, n = 171. Diagnostic accuracy was assessed by receiver operator
      characteristic curves (ROC). Corrections were made for possible confounding
      variables in the multivariate analysis. Upon ROC analysis, bilirubin showed an
      inverse relationship with risk of CAD, with areas under the ROC curve comparable
      to lipoprotein: however, bilirubin showed no discrimination below false positive
      frequencies of approximately 0.3. Logistic regression indicated that bilirubin
      was a weaker global marker than the lipoproteins and interacted with apo B. A
      highly significant correlation was found between bilirubin and apo B (p =
      0.0025), but not with cholesterol, triglycerides, or high density lipoprotein
      cholesterol. Compared to lipoprotein markers, bilirubin provides little practical
      power of discrimination for CAD. Further studies of the affect of bilirubin on
      CAD must take its interaction with apo B into consideration.

PMID- 9142371
TI  - Exchange transfusion with red blood cells preserved in adenine clears a child of
      severe falciparum malaria.
AB  - Falciparum malaria may be associated with significant morbidity and mortality.
      The degree of mortality and morbidity usually corresponds to the degree of
      parasitemia. Quinine and other antimalarial drugs are relatively slow acting and
      not always effective owing to the presence of drug resistance falciparum. Rapid
      reduction of the number of circulating parasites may be required. Exchange
      transfusion has been used as a safe and quick approach to decreasing the
      parasitemia and antimalaria drugs used to eradicate the rest of the Plasmodium.
      In the present report, a case is described of a child with severe falciparum
      malaria who was successfully treated with exchange transfusion using the new
      adenine and mannitol enriched preservative media, Adsol.

PMID- 9142372
TI  - Role of oxidative stress in the mechanism of dieldrin's hepatotoxicity.
AB  - The production of reactive oxygen species (ROS) by toxic chemicals has been
      implicated in acute and chronic disease states, including cancer. This increase
      in cellular ROS can lead to a state of oxidative stress. Many compounds
      selectively induce hepatic tumors in mice but not rats. The mechanism for the
      induction of hepatic cancer by these compounds and the observed species
      selectivity of this effect are not known but may be related to the induction of
      oxidative stress. Dieldrin is one such compound and is used in the present study
      to characterize the relationship between oxidative stress and the observed
      selective hepatotoxicity of dieldrin in mice. It was found that dieldrin induced
      oxidative stress in the mouse but not the rat, and the observed oxidative stress
      correlated with the induction of DNA S-phase synthesis. This evidence suggests
      that the induction of oxidative stress may be a mechanism by which dieldrin and
      other mouse specific compounds selectively induce their hepatic toxic effects in
      mice.

PMID- 9142373
TI  - Effects of iron complexes on brain calcium homeostasis.
AB  - The effects of two physiological low molecular weight iron complexes, ferric
      lactate and ferric adenosine triphosphate (ATP) on brain Ca2+ homeostasis
      modification, have been studied in vitro and in vivo. In vitro ferric ATP complex
      shows a higher efficiency as modifier of Ca2+ homeostasis. This higher reactivity
      and the in vivo observed effect of increased brain uptake of iron from ferric
      lactate provoked by the presence of ATP, corroborate in vitro results showing an
      iron transfer from ferric lactate to ATP, as well as the mediator role of ATP in
      the iron-induced cellular Ca2+ homeostasis modification process. The possible
      role of this process in Parkinson's disease is discussed.

PMID- 9142374
TI  - Rabies in New Hampshire and Vermont: an update.
AB  - New Hampshire and Vermont currently have two rabies epizootics occurring in
      raccoon and fox populations. These are continuations of the established raccoon
      strain which has been migrating northward from the mid-Atlantic and the fox
      strain which is migrating south and eastward from Canada and New York. These
      started in the early 1990s, and the wild animal cases have increased from 0 to 1
      case per year in Vermont in the late 1980s to 179 in 1995, and from 0 to 4 cases
      in New Hampshire to 152 in 1995. Since 1992 there has been a slight increase in
      domestic animal cases, but no human cases have been reported. The cost of
      prophylaxis and animal testing has greatly increased, including one episode where
      665 persons were exposed to a rabid kitten and underwent postexposure prophylaxis
      at an estimated cost of $1.5 million. This paper gives epidemiologic data for the
      two states and reviews the current literature to discuss history, clinical
      features, testing, postexposure prophylaxis, and treatment of rabies.

PMID- 9142375
TI  - Fluorescent in situ hybridization analysis of cervical smears. A pilot study of
      20 cases.
AB  - The Papanicolaou smear has been established as a useful cytological screening
      tool that has greatly contributed to the reduction of cervical cancer related
      mortalities. This test, however, cannot reveal underlying genetic damage, i.e.,
      numerical and structural chromosomal abnormalities that may predispose an
      individual to a future potentially life-threatening cervical neoplasm. An assay
      that has the ability to detect genetic abnormalities in interphase cervical
      mucosal cells will be a useful complement to the Papanicolaou smear on
      cytological preparations. The present project explores such a possibility using
      the technique of fluorescent in situ hybridization (FISH). The chromosome 8
      specific alpha-satellite probe is initially used because of our past experience
      in the validation of this probe in various cancers. The applicability of this
      assay, however, is not restricted to the use of this particular probe. Data on
      our initial pilot study of 20 cases revealed that such an interphase FISH assay
      is indeed feasible as a potential future screening tool for cervical cancer.

PMID- 9142376
TI  - An immunoassay for anti-neuronal antibodies associated with involuntary
      repetitive movement disorders.
AB  - Tourette's syndrome (TS) is a complex neurobehavioral disorder emerging in
      childhood and is characterized by motor and vocal tics of at least one year in
      duration. In a portion of patients with TS, environmental (non-genetic) factors
      may either have an etiologic role or act to modulate the phenotype. One possible
      environmental factor may be antibodies to central nervous system cells, as sera
      from several children diagnosed with either TS or Sydenham's chorea contained
      anti-neuronal antibodies. Using enriched membrane preparations isolated from HTB
      10 neuroblastoma cells, a sensitive and specific assay was developed for the
      determination of human anti-neuronal antibodies associated with involuntary
      repetitive movement disorders. This assay exhibited between-run and within-run
      precision of 11.3 percent and 5.9 percent, respectively. The sensitivity,
      specificity, positive predictive value, and negative predictive value of this
      assay for the diagnosis of TS and TS or chorea are 79.1 percent, 61.2 percent,
      61.6 percent, 78.8 percent, and 71.1 percent, 60.9 percent, 68.6 percent, and
      63.6 percent, respectively. In addition, there was a significant difference (p <
      0.0001) between the mean optical density in the patients with TS and children
      determined to be clinically "normal".

PMID- 9142377
TI  - Effects of reactive oxygen and nitrogen species induced by ammonium dinitramide
      decomposition in aqueous solutions of deoxyribose nucleic acid.
AB  - Ammonium dinitramide (ADN), a potential rocket fuel, decomposes in water forming
      NO2. The chemistry of this ADN-released NO2 in oxygenated biological systems is
      complex both in the number of potential chemical species and in the number of
      parallel and consecutive reactions that can theoretically occur. High-pressure
      liquid chromatography (HPLC) studies revealed ADN fragmented deoxyribose nucleic
      acid (DNA). Damage to DNA standard solutions was caused by at least two major
      pathways, one arising from reactions of NO2 with oxygen and one arising from a
      reaction with superoxide (O2-.). The radical species generated when ADN is
      incubated with standard solutions of DNA, pH 7.5, in the presence of the spin
      trap agent n-tert-butyl-alpha-nitrone (PBN) was compared with the PBN-radical
      adducts generated in the presence of ADN and O2-. or of ADN and hydrogen peroxide
      (H2O2). The ADN-induced PBN radical adducts increased linearly over the 90-minute
      study period. The values of peak intensity in the presence of O2-. and in the
      presence of H2O2, were 828% and 7.08%, respectively, of the ADN-induced radicals
      alone. The synergistic effect of ADN with O2- may provide an understanding of the
      sensitivity of the rat blastocyst to aDN at the preimplantation stage of
      development and the lack of toxicity in in vivo studies in tissues high in
      catalase.

PMID- 9142378
TI  - Risk of recurrence after treatment of early breast cancer with skin-sparing
      mastectomy.
AB  - BACKGROUND: Skin-sparing mastectomy, combined with immediate breast
      reconstruction, has become increasingly popular. However, there are no published
      long-term data to support its oncologic safety. Our purpose was to evaluate the
      long-term oncologic risk of skin-sparing mastectomy. METHODS: The records of all
      patients who had undergone treatment of T1 or T2 breast cancer by mastectomy and
      immediate breast reconstruction, and who were followed for at least 5 years or
      developed recurrence of disease before that time were reviewed. Local and distant
      recurrence rates observed in patients treated by skin-sparing mastectomy were
      compared with those in patients treated by conventional, non-skin-sparing
      mastectomy. RESULTS: A total of 104 patients were treated with skin-sparing
      mastectomies. In that group, 6.7% developed local recurrences, 12.5% developed
      distant metastases, 88.5% remained free of disease, and 7.7% died of their
      disease. Among the 27 patients who did not have skin-sparing mastectomies. 7.4%
      had local recurrences, 25.9% had distant metastases, 74.1% remained free of
      disease, and 18.5% died of disease. These recurrence rates are similar to those
      reported elsewhere after treatment with conventional mastectomy and without
      reconstruction. CONCLUSIONS: Our findings suggest that skin-sparing mastectomy
      does not significantly increase the risk of local or systemic disease recurrence
      in patients with early breast cancer.

PMID- 9142379
TI  - Bilaterality and recurrence rates for lobular breast cancer: considerations for
      treatment.
AB  - BACKGROUND: The purpose of this study was to evaluate the tumor biology with
      respect to bilaterality and recurrence rates for bilateral infiltrating lobular
      (IL) breast carcinoma in comparison with other histological types. METHODS: A
      prospectively accrued data base containing 1,548 breast cancer cases as well as
      H. Lee Moffitt Cancer Center's cancer registry compiled during the same period
      were queried for specific features relating to bilaterality and recurrence. The
      116 patients in this study had been treated at the Comprehensive Breast Cancer
      Clinic and had documented bilateral breast cancer (invasive on situ). RESULTS:
      Eighty-two of the patients (70.7%) had metachronous breast cancer, and 34 (29.3%)
      had synchronous cancer. Although median follow-up times were short, the risk of
      developing breast cancer in the contralateral breast after the diagnosis of
      cancer in the ipsilateral breast was estimated to be 0.7% per patient-year of
      follow-up. Recurrence rates for IL cancers were compared with those for invasive
      ductal (ID) and for ID + IL cancers. IL cancers recurred 8.1% of the time,
      whereas ID cancers recurred at a rate of 7.8%. Recurrences were equally divided
      between local and distant sites. CONCLUSIONS: Although IL cancers have
      demonstrated insidious behavior, their incidence of bilaterality is only slightly
      higher than other histologies and their rates of recurrence are low when properly
      evaluated and treated. The risk to the opposite breast also appears to be low.
      These data do not support the routine use of blind contralateral biopsy or
      prophylactic mastectomy.

PMID- 9142380
TI  - Combined intensive chemotherapy and radical surgery for incurable gastric cancer.
AB  - BACKGROUND: To improve the poor prognosis of patients with advanced incurable
      gastric cancer, intensive chemotherapy combined with radical surgery was used.
      PATIENTS AND METHODS: Thirty patients with incurable gastric cancer were treated
      with a combination of 5-fluorouracil (370 mg/m2) and leucovorin (30 mg/person),
      given intravenously for five consecutive days, followed by cisplatinum (70 mg/m2)
      and etoposide (70 mg/m2) on days 6 and 20, delivered through a catheter placed
      either in the aorta with its tip at the level of the ninth thoracic vertebra or
      in the celiac artery. This treatment (FLEP therapy) was repeated twice every 5
      weeks. Radical or palliative surgery followed chemotherapy. RESULTS: The overall
      response rate to the chemotherapy was 50.0% (15 of 30 patients, 95% confidence
      limit 0.305-0.671). Nineteen patients (15 with a partial response, three showing
      no change, and one with progressive disease) underwent surgery. Of these, nine
      underwent curative surgery and 10 palliative surgery. The median survival time
      was 6.5 months overall, 12.7 months for responders, and 4.7 months for
      nonresponders. Long-term survivors were exclusively found among patients with
      distant lymph node metastasis treated by curative surgery (55.6% at 5 years).
      CONCLUSIONS: Favorable results of this small phase II study justify a phase III
      trial.

PMID- 9142381
TI  - Extended surgery--left upper abdominal exenteration plus Appleby's method--for
      type 4 gastric carcinoma.
AB  - BACKGROUND: The prognosis after surgical treatment for type 4 gastric cancer,
      including linitis plastica, remains poor. The most frequent recurrence mode is
      retroperitoneal involvement. To remove the tumor and microinvasion surrounding
      the stomach, extended surgery, left upper abdominal exenteration plus the
      Appleby's method (LUAE + Apl), has been performed for type 4 cancers since 1983.
      PATIENTS AND METHODS: A total of 54 patients with type 4 cancer underwent
      extended surgery (LUAE + Apl) over the past 11 years. In the LUAE + Apl surgical
      procedure, the whole stomach, pancreas body and tail, spleen, gallbladder,
      transverse colon, and left adrenal were removed en bloc. The results of this
      treatment are reported and the most beneficial application of this procedure
      (group A) is evaluated and compared with findings in similar patients who
      underwent common surgery between 1973 and 1983 (group B). RESULTS: As
      postoperative complications, pancreatic fistula (30%; control 19%), liver
      dysfunction (15%; 14%), anastomosis failure (6%; 9%), and infection (4%; 1%) were
      observed (NS). In group A, one patient died of liver dysfunction and another of
      multiple organ failure due to major pancreatic fistula. In stage III, the 5-year
      survival rate of group A (40%) was better than that of group B (20%; p < 0.05).
      In stage IV, the 5-year survival rate of group A (5%; 3% in group B) was not
      improved. CONCLUSION: LUAE + Apl improved the survival of patients with scirrhous
      cancer in stage III, but it was not effective for those in stage IV. To improve
      the survival of patients in stage IV, a new concept of treatment and supportive
      therapy needs to be used.

PMID- 9142382
TI  - Surgically debulked malignant pleural mesothelioma: results and prognostic
      factors.
AB  - BACKGROUND: We analyzed morbidity and mortality, sites of recurrence, and
      possible prognostic factors in 95 (78 male, 17 female) patients with MPM on phase
      I-III trials since 1990. A debulking resection to a requisite, residual tumor
      thickness of < or = 5 mm was required for inclusion. METHODS: Preoperative tumor
      volumes were determined by three-dimensional reconstruction of chest computerized
      tomograms. Pleurectomy (n = 39) or extrapleural pneumonectomy (EPP; n = 39) was
      performed. Seventeen patients could not be debulked. Preoperative EPP platelet
      counts (404,000) and mean tumor volume (491 cm3) were greater than that seen for
      pleurectomy (344,000, 114 cm3). RESULTS: Median survival for all patients was
      11.2 months, with that for pleurectomy 14.5 months, that for EPP 9.4 months, and
      that for unresectable patients 5.0 months. Arrhythmia (n = 14; 15%) was the most
      common complication, and there were two deaths related to surgery (2.0%). Tumor
      volume of > 100 ml, biphasic histology, male sex, and elevated platelet count
      were associated with decreased survival (p < 0.05). Both EPP and pleurectomy had
      equivalent recurrence rates (27 of 39 [69%] and 31 of 39 [79%], respectively);
      however, 17 of 27 EPP recurrences as opposed to 28 of 31 pleurectomy recurrences
      were locoregional (p2 = 0.013). CONCLUSIONS: Debulking resections for MPM can be
      performed with low operative mortality. Size and platelet count are important
      preoperative prognostic parameters for MPM. Patients with poor prognostic
      indicators should probably enter nonsurgical, innovative trials where toxicity or
      response to therapy can be evaluated.

PMID- 9142383
TI  - Leiomyosarcoma in childhood and adolescence.
AB  - BACKGROUND: Few series of leiomyosarcoma in patients < 21 years of age have been
      reported. We reviewed our institutional experience with this neoplasm to learn
      disease characteristics, patterns of relapse, and outcome. METHODS: The records
      of 21 patients with leiomyosarcoma admitted to our institution were reviewed
      retrospectively; 18 of these were diagnosed after 1970. Overall survival was
      estimated using the Kaplan-Meier method. RESULTS: Ninety-five percent (20 of 21)
      were initially treated with a wide local excision that was complete with a
      negative microscopic margin in 10 (48%). There also was a strong correlation
      between grade and surgical margins. High-grade tumors were associated with a
      lower rate of complete resection. The majority underwent additional therapy.
      Radiation was used to treat both initial and recurrent disease in nine patients,
      with four of these undergoing brachytherapy. Thirteen patients were treated with
      adjuvant chemotherapy, most commonly doxorubicin (seven patients) and cisplatin
      (six patients). The median length of survival was 9.3 years, and there were nine
      disease-related deaths (43%). Of interest was the progressive decrease in
      survival with time. The 5-year overall survival rate was 79%; the 10-year rate
      was 49%. Three patients died of progressive disease > 10 years after initial
      diagnosis. CONCLUSIONS: We conclude that leiomyosarcomas arising in childhood and
      adolescence are associated with a good initial chance of survival that decreases
      progressively over time. Known prognostic factors from larger adult series are
      consistent with the present data, but they are not provable because of the small
      number of patients. In particular, the grade was correlated with surgical
      margins.

PMID- 9142384
TI  - Needle tract recurrences after closed biopsy for sarcoma: three cases and review
      of the literature.
AB  - BACKGROUND: Percutaneous closed needle biopsy of musculoskeletal neoplasms has
      gained in popularity. However, it remains controversial whether or not to resect
      the needle tract for fear of a local recurrence. A single published case report
      exists, noting the lone tract recurrence of an extremity skeletal osteosarcoma.
      METHODS: We report on three additional individuals who demonstrated that tract
      local recurrences may occur after a closed needle biopsy for nonosteosarcoma,
      nonextremity sarcomas. For perspective, the world literature is reviewed to
      identify tract recurrences for other malignancies and the results of needle
      biopsy in musculoskeletal neoplasms. RESULTS: Eighty-nine percent of needle tract
      local recurrences occur when carcinomas are subjected to biopsy, as reported in
      the literature. Forty-seven cases since 1950 are described representing
      essentially all tumor types. The nature of musculoskeletal neoplasms makes closed
      biopsy more difficult than for softer, more homogeneous, and easier to access
      neoplasms. CONCLUSIONS: Local recurrences of sarcoma may occur in closed needle
      biopsy tracts. Strong consideration should be given to open biopsy and tract
      resection.

PMID- 9142386
TI  - Lymphoscintigraphy as a predictor of lymphatic drainage from cutaneous melanoma.
AB  - BACKGROUND: If cutaneous lymphoscintigraphy (CL) is accurate in predicting the
      draining lymph node basins at risk from primary axial melanomas, then regional
      metastases should only occur in those lymph node basins identified by CL.
      METHODS: This study is a retrospective review of patients undergoing CL for
      primary axial melanomas from June 1, 1985, until June 31, 1992. Data retrieved
      included age, gender, number of basins identified, location of basins identified,
      management of basins, recurrence in lymphatics, development of distant disease,
      and long-term follow-up. RESULTS: A total of 181 patients underwent elective LND,
      and 48 patients (27%) had melanoma in the nodes within the dissected basin. Of
      these 181 patients, seven developed nodal metastases as their site of first
      recurrence. All seven recurrences were seen at sites dissected or at sites
      indicated by CL, which the primary surgeon elected not to treat initially. Of the
      116 patients observed, 16 (14%) developed lymph node metastases as their first
      site of recurrence. Fifteen of these 16 patients had their site of lymph node
      metastases predicted by CL. In this study, CL predicted 98.6% of all lymph node
      metastases. CONCLUSIONS: The high overall reliability of CL as demonstrated by
      long-term follow-up indicates that the information obtained by CL can be reliably
      used to guide intervention. Initial evaluation of patients with high-risk
      cutaneous melanomas at sites with ambiguous lymphatic drainage must include CL in
      order to determine the draining lymph node basins and to plan therapy.

PMID- 9142385
TI  - Distal upper extremity function following proximal humeral resection and
      reconstruction for tumors: contralateral comparison.
AB  - BACKGROUND: Most functional analyses after limb salvage operations about the
      shoulder have focused on proximal function with the assumption that distal
      function is largely unaffected. This analysis examines distal function
      objectively. METHODS: Objective laboratory data regarding distal upper extremity
      strength after reconstructive procedures for tumors near the shoulder joint was
      collected over a 16-year period. Thirty-two patients were able to participate
      fully in the data collection at an average most recent follow-up duration of >
      3.5 years. RESULTS: Statistically significant reductions on the involved side
      compared with the uninvolved side in grip, forearm pronation, forearm supination,
      elbow flexion, and elbow extension strength were documented (p < 0.05). The
      magnitude of reduction in strength diminishes distally, with the greatest effect
      in this group of patients being observed in elbow extension, followed by elbow
      flexion, forearm supination, and forearm pronation. Grip strength consistently
      showed the least amount of strength reduction compared with the uninvolved side,
      even within resection and reconstruction groups. Subjective patient rating of
      dexterity was no less than 3 of 5. Ninety percent of patients rated their
      dexterity 4 of 5 (52%) or 5 of 5 (38%). CONCLUSIONS: Despite the insistence of
      "normal" function in the distal upper extremity after limb salvage procedures,
      complete normality is not maintained. However, the degree of maintenance of
      distal function appears to be high, especially for grip strength and forearm
      pronation strength, and patient satisfaction is acceptable.

PMID- 9142387
TI  - Computed tomography in evaluation of patients with stage III melanoma.
AB  - BACKGROUND: Metastatic disease is detected infrequently by computed tomography
      (CT) in early stage melanoma. The diagnostic yield of routine CT for stage III
      melanoma is less established, despite extensive use in clinical practice.
      METHODS: Charts from 347 asymptomatic patients with stage III melanoma were
      reviewed. Findings suggestive of metastatic melanoma identified by head or body
      CT, chest radiography, bone scan, or liver function studies were confirmed
      histologically or by progression of disease. RESULTS: Individual CT scans
      identified 33/788 (4.2%) instances of metastatic melanoma, with 66/788 (8.4%)
      false positive studies. No metastases were identified among 104 head CT scans.
      Chest CT had the highest yield in patients with cervical adenopathy (7/35, 20%),
      and the lowest yield with groin adenopathy (1/50, 2%). Pelvic CT diagnosed
      metastases in 7/94 (7.4%) patients with groin adenopathy, but no patients with
      palpable axillary (n = 76) or cervical (n = 21) nodes. Metastatic melanoma was
      diagnosed in 11/136 (8.1%) patients having complete body CT imaging (chest,
      abdomen, and pelvis), including six patients (4.4%) identified by CT alone.
      CONCLUSIONS: Routine CT in patients with clinical stage III melanoma infrequently
      identifies metastatic disease. Head CT in the asymptomatic patient, chest CT in
      patients with groin adenopathy, and pelvic CT in the presence of axillary or
      cervical adenopathy are not indicated. Selective use of chest CT in patients with
      cervical adenopathy or pelvic CT in the presence of groin disease may be useful.

PMID- 9142388
TI  - Predictors of breast-conserving surgery in Connecticut, 1990-1992.
AB  - BACKGROUND: Breast-conserving surgery (BCS) has been recommended for most early
      stage primary breast cancers, but predictors may vary by time and geographic
      area. METHODS: Among 5,266 early-stage female breast cancers (diagnosed in 1990
      1992) in the population-based Connecticut Tumor Registry, the poverty rate of
      census tract of residence (an ecologic indicator of socioeconomic status), age at
      diagnosis, race, marital status, extent of disease, year of diagnosis, and town
      of residence were analyzed in relation to BCS use. RESULTS: The poverty rate of
      census tract was not a statistically significant variable in logistic regression
      analyses of BCS use; however, age, year of diagnosis, and stage at diagnosis were
      predictors. Residence in a town with a hospital having radiotherapy facilities or
      near a university hospital were not predictors of BCS use. High BCS rates (69-94%
      vs. 49% statewide) were found for residents of a cluster of seven contiguous
      towns associated with a single (nonuniversity) hospital. CONCLUSIONS: BCS was not
      associated with poverty level of area of residence but continued to be lower for
      larger or node-positive cancers. Attitudes and practices of local physicians were
      hypothesized as being important in explaining variation in BCS use by town of
      residence.

PMID- 9142389
TI  - Overexpression of focal adhesion kinase (p125FAK) in human colorectal carcinoma
      liver metastases: independence from c-src or c-yes activation.
AB  - BACKGROUND: p125FAK, pp60C-src, and pp62c-yes are protein tyrosine kinases that
      function in signaling pathways regulating cell adhesion, migration, and growth.
      The expression and tyrosine kinase activities of pp60c-src and pp62c-yes, and the
      expression of p125FAK are increased in colorectal tumor metastases relative to
      normal mucosa. This study investigates whether differences in the activation of
      pp60c-src and pp62c-yes in colorectal liver metastases correlated with
      differences in p125FAK expression and whether prognostic significance could be
      demonstrated from the extent of expression of p125FAK in metastases. METHODS:
      Activities of pp60c-src and pp62c-yes were measured in the immune complex kinase
      assay. Relative levels of p125FAK, pp60c-src, and pp62c-yes were determined by
      immunoblotting. RESULTS: p125FAK was overexpressed in 29 of 30 colorectal cancer
      liver metastases (range of two-to 195-fold increase compared with normal mucosa).
      The degree of overexpression of p125FAK was not a significant prognostic factor
      in survival. A differential activation of pp60c-src and pp62c-yes in colorectal
      carcinoma liver metastases was observed. However, overexpression of p125FAK was
      observed in metastases with either pp60c-src or pp62c-yes activated in colorectal
      carcinoma liver metastases. CONCLUSIONS: p125FAK overexpression appears to be a
      marker present in colorectal cancer cells with a metastatic phenotype.
      Furthermore, p125FAK overexpression is independent of pp60c-src or pp62c-yes
      activation in human colorectal carcinoma liver metastases.

PMID- 9142390
TI  - Topographic genotyping of colorectal carcinoma: from a molecular carcinogenesis
      model to clinical relevance.
AB  - BACKGROUND: In recent years, as a result of refinement in molecular biology
      techniques, significant progress has been made in the understanding of colorectal
      carcinogenesis. Particular attention has been drawn to identification of genetic
      mutation that may predispose to colorectal carcinoma (familial syndromes) and may
      affect tumor behavior and prognosis (sporadic cases). CONCLUSIONS: Our method of
      topographic genotyping of human colonic carcinomas has shown a correlation
      between K-ras-2 and p53 mutations and stage at diagnosis as well as long-term
      survival. Data from other investigators in this field confirm the importance of
      genetic analysis of human colorectal tumors. These findings are likely to impact
      management by allowing a more individualized therapeutic approach.

PMID- 9142391
TI  - Complications of mastectomy.

PMID- 9142392
TI  - Variation in cutaneous lymphatic flow rates.

PMID- 9142394
TI  - pA, a new scale for the measurement of drug antagonism. 1947.

PMID- 9142393
TI  - Observations on the isolated phrenic nerve diaphragm preparation of the rat.
      1946.

PMID- 9142395
TI  - Curare-like action of polymethylene bis-quaternary ammonium salts. 1948.

PMID- 9142396
TI  - The pharmacological actions of polymethylene bistrimethylammonium salts. 1949.

PMID- 9142397
TI  - The technique of superfusion. 1953.

PMID- 9142398
TI  - A pharmacological analysis of the mode of action of serotonin (5
      hydroxytryptamine) upon the guinea-pig ileum. 1952.

PMID- 9142399
TI  - A modification of receptor theory. 1956.

PMID- 9142400
TI  - The action of morphine and related substances on contraction and on acetylcholine
      output of coaxially stimulated guinea-pig ileum. 1956.

PMID- 9142401
TI  - Two kinds of tryptamine receptor. 1957.

PMID- 9142402
TI  - A sensitive method for the assay of 5-hydroxytryptamine. 1957.

PMID- 9142403
TI  - Some quantitative uses of drug antagonists. 1958.

PMID- 9142404
TI  - The actions of bretylium: adrenergic neurone blocking and other effects. 1959.

PMID- 9142406
TI  - Responses of the isolated sympathetic nerve-ductus deferens preparation of the
      guinea-pig. 1961.

PMID- 9142405
TI  - Sympathetic postganglionic cholinergic fibres. 1959.

PMID- 9142407
TI  - Actions of amino-acids on the isolated hemisected spinal cord of the toad. 1961.

PMID- 9142408
TI  - Actions of triethylcholine on neuromuscular transmission. 1961.

PMID- 9142409
TI  - The use of isolated organs for detecting active substances in the circulating
      blood. 1964.

PMID- 9142410
TI  - The uptake of catechol amines at high perfusion concentrations in the rat
      isolated heart: a novel catechol amine uptake process. 1964.

PMID- 9142412
TI  - Receptors mediating some actions of histamine. 1966.

PMID- 9142411
TI  - Comparison of some properties of pronethalol and propranolol. 1965.

PMID- 9142413
TI  - The action of acetylcholine and other drugs on the efflux of potassium and
      rubidium from smooth muscle of the guinea-pig intestine. 1968.

PMID- 9142414
TI  - Evidence that adenosine triphosphate or a related nucleotide is the transmitter
      substance released by non-adrenergic inhibitory nerves in the gut. 1970.

PMID- 9142416
TI  - The rat anococcygeus muscle and its response to nerve stimulation and to some
      drugs. 1973.

PMID- 9142415
TI  - Role of the alpha-adrenoceptor in regulating noradrenaline overflow by nerve
      stimulation. 1971.

PMID- 9142417
TI  - A new example of a morphine-sensitive neuro-effector junction: adrenergic
      transmission in the mouse vas deferens. 1972.

PMID- 9142419
TI  - Kinetics of agonist conductance changes during hyperpolarization at frog
      endplates. 1974.

PMID- 9142418
TI  - Prostaglandins and the mechanism of analgesia produced by aspirin-like drugs.
      1973.

PMID- 9142420
TI  - An analysis of the depressor responses to histamine in the cat and dog:
      involvement of both H1- and H2-receptors. 1975.

PMID- 9142421
TI  - The distribution of methionine-enkephalin and leucine-enkephalin in the brain and
      peripheral tissues. 1977.

PMID- 9142422
TI  - Prostacyclin (PGI2) inhibits the formation of platelet thrombi in arterioles and
      venules of the hamster cheek pouch. 1977.

PMID- 9142423
TI  - Antagonist discrimination between ganglionic and ileal muscarinic receptors.
      1980.

PMID- 9142424
TI  - Characteristics of GABAB receptor binding sites on rat whole brain synaptic
      membranes. 1983.

PMID- 9142427
TI  - Dale and the development of pharmacology. 1975.

PMID- 9142425
TI  - The channel-blocking action of methonium compounds on rat submandibular ganglion
      cells. 1983.

PMID- 9142428
TI  - Recent changes in the treatment of congestive heart failure. Introduction.

PMID- 9142426
TI  - Bioassay of prostacyclin and endothelium-derived relaxing factor (EDRF) from
      porcine aortic endothelial cells. 1985.

PMID- 9142429
TI  - Current concepts in the treatment of congestive heart failure.
AB  - Heart failure is a complex syndrome; therapy should be aimed at the independent
      goals of prolonging life and of improving symptoms and quality of life. Some
      therapies are effective in achieving one goal but not the other. Short-term
      symptomatic relief may relate to alleviation of haemodynamic abnormalities and of
      congestion, whereas slowing progression of the disease and reducing mortality
      involve neurohormonal mechanisms, left ventricular remodelling and arrhythmia
      generation. Current therapy is moderately effective on these end-points, but
      newer approaches to management are necessary to produce more profound
      improvements in morbidity and mortality.

PMID- 9142430
TI  - The effect of positive inotropes on the failing human myocardium.
AB  - Heart failure is associated with pathobiochemical changes that can reduce the
      responsiveness of the myocardium to positive inotropic agents. We studied the
      contractile effects of a range of inotropic agents on papillary muscle strips
      from healthy and failing human hearts. Specimens were obtained from patients with
      different grades of heart failure. These included individuals undergoing mitral
      valve replacement (New York Heart Association Class II-III) or receiving heart
      transplantation (New York Heart Association Class IV). Heart failure was
      associated with attenuation of myocardial contractile responses to dobutamine,
      histamine, 3-isobutyl-1-methylxanthine, and the phosphodiesterase inhibitors,
      milrinone and pimobendan. However, pretreatment of the papillary muscle with
      isoprenaline augmented the positive inotropic effect observed with the
      phosphodiesterase inhibitors. The contractile response to ouabain was not
      influenced by the presence of heart failure. We conclude that, unlike beta
      adrenoceptors, cardiac glycoside receptors in the myocardium are not down
      regulated in the presence of heart failure.

PMID- 9142431
TI  - New inotropic concepts: rationale for and differences between calcium sensitizers
      and phosphodiesterase inhibitors.
AB  - Positive inotropic compounds may be harmful in the long-term treatment of chronic
      congestive heart failure because they may induce a calcium overload, unwanted
      changes in cross-bridge kinetics and an acceleration in heart rate. As a result
      of all three alterations, energy consumption would be increased. Different
      pharmacological modes of action may have different effects on the molecular
      mechanisms underlying the positive inotropic effect, and hence on myocardial
      energy consumption. Therefore, we studied the effects of a variety of cardiotonic
      agents on the heat released from small guinea pig papillary muscles contracting
      isometrically at an experimental temperature of 21 degrees C and a stimulation
      frequency of 12 per minute using rapid antimony-bismuth thermopiles. We were able
      to define the economy of muscle contraction, which was lowest with
      phosphodiesterase inhibitors and highest with calcium sensitizers. Compared with
      an increase in extracellular calcium concentration, beta 1-adrenoceptor
      stimulators and phosphodiesterase inhibitors profoundly decrease the economy of
      myocardial contraction, and calcium-sensitizers (pimobendan and EMD-53998)
      slightly increase myocardial economy, whereas ouabain and the calcium channel
      agonist BAY K 8644 have no effect on this parameter. In addition, we provide
      evidence that acceleration of heart rate may be harmful not only from an
      energetic point of view: an increase in heart rate may also decrease the
      contractility of the failing human myocardium (inverse force-frequency
      relationship). Taking these observations into consideration, an "optimal'
      positive inotropic compound should have no, or even negative, chronotropic
      effects, should not be mediated by increases in calcium transients, and should
      decelerate, rather than accelerate, cross-bridge kinetics.

PMID- 9142432
TI  - Effects of pimobendan on exercise tolerance and quality of life in patients with
      heart failure.
AB  - There has been an intensive search for safe and clinically effective inotropic
      agents for use as adjunctive therapy in patients with advanced heart failure.
      Pimobendan is a benzimidazole-pyridazinone derivative with calcium-sensitizing
      properties that increases myocardial contractile force without increasing
      intracellular calcium. This review summarizes the data from five controlled,
      randomized prospective trials of pimobendan that demonstrate significant
      improvements in exercise capacity and quality of life in patients with heart
      failure. The clinical benefits of pimobendan found in these trials contrast with
      the adverse experience noted previously with milrinone and enoximone. This may be
      related to the different mechanism of action of pimobendan or to a study design
      that permitted examination of a lower dosage. These cumulative data suggest that
      pimobendan may have a useful adjunctive role in heart failure and that further
      assessment of its effects on overall mortality is needed.

PMID- 9142433
TI  - Clinical efficacy and safety of pimobendan in treatment of heart failure-
      experience in Japan.
AB  - The results of Japanese studies on the clinical efficacy and safety of pimobendan
      in the treatment of heart failure are summarized in this paper. In patients with
      acute heart failure, a single oral 2.5 mg dose of pimobendan produced a
      significant increase in cardiac index (27.9%) and stroke volume index (24.4%), as
      well as a significant decrease in pulmonary capillary wedge pressure (-21.3%). A
      single oral 5.0 mg dose of pimobendan increased anaerobic threshold during
      exercise (7.3%). In a multicentre, placebo-controlled, double-blind trial, 8
      weeks of treatment with pimobendan 2.5 mg b.i.d., which was suggested to be the
      optimal dose in a preceding dose-finding study, definitely improved symptoms and
      signs of heart failure in 52.6% of patients, and New York Heart Association
      function class in 64.1% of patients. This regimen was also associated with a
      significantly greater increase in physical activity than placebo. Furthermore,
      another double-blind, placebo-controlled study suggested that pimobendan 1.25 mg
      and 2.5 mg b.i.d. may have long-term beneficial effects on morbidity and quality
      of life in patients with chronic heart failure. Adverse reactions developed in 26
      of 241 (10.8%) patients receiving multiple doses of pimobendan, but none of the
      reactions were serious. It is concluded that pimobendan may be useful in the
      treatment of patients with heart failure.

PMID- 9142434
TI  - Traction fibre: toward a "tensegral" model of the spindle.
AB  - Most current hypotheses of mitotic mechanisms are based on the "PAC-MAN" paradigm
      in which chromosome movement is generated and powered by disassembly of
      kinetochore microtubules (k-MTs) by the kinetochore. Recent experiments
      demonstrate that this model cannot explain force generation for anaphase
      chromosome movement [Pickett-Heaps et al., 1996: Protoplasma 192:1-10]. Another
      such experiment is described here: a UV-microbeam cut several kinetochore fibres
      (k-fibres) in newt epithelial cells at metaphase and the half-spindle immediately
      shortened: in several cells, the remaining intact spindle fibres bowed outwards
      as they came under increased compression. Thus, severing of k-MTs can lead to
      increased tension between chromosomes and poles. This observation cannot be
      explained by models in which force is produced by motor molecules at the
      kinetochore actively disassembling k-MTs. Rather, we argue that tensile forces
      act along the whole k-fibre, which, therefore, can be considered as a classic
      "traction fibre." We suggest that anaphase polewards force is generated by MTs
      interacting with the spindle matrix and when k-MTs are severed, polewards force
      continues to act on the remaining kMT-stub; spindle MTs act as rigid struts
      concurrently resisting and being controlled by these forces. We suggest that the
      principles of "cellular tensegrity" [Ingber, 1993: J. Cell Sci. 104:613-627]
      derived from the behaviour and organization of the interphase cell apply to the
      spindle. In an evolutionary context, this argument further suggests that the
      spindle might originally have evolved as the mechanism by which a single
      tensegral unit (cytoplast) is divided into two cytoplasts; use of the spindle for
      segregating chromosomes might represent a secondary, more recent development of
      this primary function. If valid, this concept has implications for the way the
      spindle functions and for the spindle's relationship to cytokinesis.

PMID- 9142435
TI  - Two populations of beta-spectrin in rat skeletal muscle.
AB  - We use immunoblotting, immunoprecipitation, and centrifugation in sucrose density
      gradients to show that the product of the erythrocyte beta-spectrin gene in rat
      skeletal muscle (muscle beta-spectrin) is present in two states, one associated
      with fodrin, and another that is not associated with any identifiable spectrin or
      fodrin subunit. Immunofluorescence studies indicate that a significant amount of
      beta-spectrin without alpha-fodrin is present in the myoplasm of some muscle
      fibers, and, more strikingly, at distinct regions of the sarcolemma. These
      results suggest that alpha-fodrin and muscle beta-spectrin associate in muscle in
      situ, but that some muscle beta-spectrin without a paired alpha-subunit forms
      distinct domains at the sarcolemma.

PMID- 9142436
TI  - Effects of nanomolar taxol on crane-fly spermatocyte spindles indicate that
      acetylation of kinetochore microtubules can be used as a marker of poleward
      tubulin flux.
AB  - Kinetochore microtubules (kMTs) in meiosis-I crane-fly spermatocytes label
      strongly with antibodies to acetylated alpha-tubulin, except near the
      kinetochore, where there is a "gap" in labelling [Wilson and Forer, 1989: Cell
      Motil. Cytoskeleton 14:237-250]. Previously we measured the length of gaps in
      metaphase and anaphase cells, and from these data deduced that during anaphase
      kMTs disassemble primarily at the pole [Wilson et al., 1994: J. Cell Sci.
      107:3015-3027]. However, the study rested on our assumption that the gap is due
      to a time lag between polymerisation at the kinetochore and acetylation of the
      polymerised MTs: the subunits enter kMTs at the kinetochore and do not become
      acetylated until they have moved poleward. In the present study we tested our
      interpretation of the gap by treating spermatocytes with paclitaxel (taxol) to
      reduce microtubule dynamics [e.g. Jordan et al., 1993: Proc. Natl. Acad. Sci.
      U.S.A. 90:9552-9556]. We expected that if our assumptions were correct, taxol
      would slow tubulin addition at the kinetochore but acetylation would continue,
      and the gap in acetylation would get smaller. We found that 5 to 50 nM taxol
      results in increased acetylation of kMTs at the kinetochore, supporting our
      interpretation of the gap. Nanomolar taxol also increases the level of
      acetylation in other microtubule populations and causes changes in spindle
      morphology.

PMID- 9142437
TI  - Cell migration and proliferation during the in vitro wound repair of the
      respiratory epithelium.
AB  - The respiratory epithelium is frequently injured by inhaled toxic agents or by
      micro-organisms. The epithelial wound repair represents a crucial process by
      which surface respiratory cells maintain the epithelial barrier integrity. The
      repair process involves both cell migration and proliferation, but as yet, the
      kinetic of these two mechanisms has not been extensively studied. Using an in
      vitro model of human respiratory epithelium wound repair, proliferative cell
      immunofluorescent staining and a computer-assisted technique allowing the
      tracking of living cells, we studied the cell proliferation and migration during
      the wound repair process. Respiratory epithelial cells were dissociated from
      human nasal polyps and cultured on a collagen I matrix. At confluency, a chemical
      wound was made on the culture. We observed that the cell mitotic activity peaked
      at 48 h after wounding (23% of the cells) and mainly concerned the cells located
      160 to 400 microns from the wound edge. The migration speed was highest (35 to 45
      microns/h) for the spreading cells at the wound edge and progressively decreased
      for the cells more and more distant from the wound edge. The temporal analysis of
      the cell migration speed during the wound repair showed that it was almost
      constant during the first 3 days of the repair mechanism and thereafter dropped
      down until the wound closure was completed (after 4 days). We also observed that
      over a 1-hour period, the intra-individual and interindividual variation of the
      cell migration speed was 43% and 37%, respectively. These results demonstrate
      that cell proliferation and cell migration during respiratory epithelial wound
      repair are differently expressed with regard to the cell location within the
      repairing area.

PMID- 9142438
TI  - Shigella actin-based motility in the absence of vinculin.
AB  - Reports on the role of vasodilator-stimulated phosphoprotein (VASP) and proline
      rich sequences in actin-based motility of Listeria and potentially of Shigella
      flexneri have led to the suggestion that vinculin might be an essential docking
      protein on the surface O2 motile Shigella. Therefore, whether vinculin had a
      functional role in Shigella actin-based motility was tested by examining Shigella
      infection of the vinculin-deficient F9 cell line variant 5.51. Shigella are able
      to form actin tails and surface protrusions in 5.51 cells that are
      indistinguishable from those they produce in F9 cells, and Shigella rates of
      intracellular movement and protrusion formation are similar in the two cell
      lines. These data disprove the model of Shigella actin-based motility in which
      vinculin is an essential docking protein for either the formation of actin tails
      or the acceleration of motile bacteria.

PMID- 9142439
TI  - Actin dynamics and organization during growth cone morphogenesis in Helisoma
      neurons.
AB  - Growth cone formation at the terminal region of severed axons is a fundamental
      step in neuronal regeneration. To understand the cytoskeletal events underlying
      this process, we have followed actin organization and dynamics as the severed,
      axonal stumps of Helisoma neurons transformed into mature growth cones. We
      identified three stages in growth cone morphogenesis: (1) formation, (2)
      expansion, and (3) maturation. The formation stage involved cytochalasin B
      insensitive terminal swelling formation, followed by cytochalasin B-inhibited
      filopodial and lamellipodial formation. Time-lapse images of neurons injected
      with labeled actin showed actin ribs in nascent growth cones formed both by
      incorporation of filopodial actin bundles and de novo assembly at the leading
      edge. Phallacidin-stained growth cones revealed F-actin to be organized into
      bundles (ribs) and a meshwork throughout morphogenesis. Actin ribs represented
      the dominant F-actin population during the expansion stage and the early phase of
      maturation, whereas a meshwork organization dominated the late phase of
      maturation. During the expansion stage, growth cones exhibited a rapid retrograde
      flow (4.8 microns/min), as assessed with flow-coupled latex beads, and
      comparatively slow lamellipodial protrusion (0.3 micron/min). During the
      maturation stage, no net lamellipodial advancement occurred; however, the rate of
      retrograde flow was significantly faster in the early phase (5.0 microns/min)
      than the late phase (2.3 microns/min). This decrease in retrograde flow
      corresponded with a change in actin organization. Lateral movements of actin ribs
      (2.1 microns/min) also occurred throughout growth cone morphogenesis, but were
      most prominent during the expansion stage. These experiments provide evidence for
      de novo actin assembly during growth cone formation and demonstrate that temporal
      changes in actin organization and dynamics accompany growth cone morphogenesis.

PMID- 9142440
TI  - Purification and characterization of basal apparatuses from a flagellate green
      alga.
AB  - Basal apparatuses consisting of two basal bodies and several attached fibers were
      isolated from the naked green flagellate Spermatozopsis similis by detergent
      extraction and mechanical disintegration. Sucrose density centrifugation yielded
      highly enriched basal apparatuses as shown by electron microscopy. SDS-PAGE
      revealed the absence of histones, indicating the removal of nuclear
      contaminations from the isolated basal apparatuses. A mass spectrometric analysis
      of the carboxyterminal peptides of alpha tubulin documented detyrosination and
      glutamylation as posttranslational modifications and showed that some 5% of the
      alpha tubulin carries a polyglutamyl side chain which can reach at least 17
      residues in length. Monoclonal antibodies raised against the purified basal
      apparatuses were used to characterize novel components in the basal apparatus. A
      210-kD component identified by mAB BAS (basal apparatus of Spermatozopsis) 1.4
      was localized in the flagellar transitional region by immunogold electron
      microscopy. Antibody BAS 16.4 reacted with two high molecular weight bands
      (approximately 265 and 240 kD) in Western blotting and decorated a fiber attached
      to the proximal end of the basal bodies. Immunofluorescence staining of isolated
      cytoskeletons with these mABs demonstrated that the antigens are also present in
      the basal apparatuses of Chlamydomonas reinhardtii and Dunahella bioculata. These
      antibodies are useful tools for the molecular cloning of components from the
      basal apparatus.

PMID- 9142441
TI  - Control of inflammatory damage by anti-LFA-1: increase success of myoblast
      transplantation.
AB  - Myoblast transplantation is a potential treatment for Duchenne Muscular
      Dystrophy. This article confirms by experiments in mice that one problem that has
      limited the success of clinical trials of this procedure is a rapid (within 3
      days) inflammatory reaction which kills most of the injected myoblasts. The death
      of the transplanted myoblasts can be prevented by treating the host with a mAb
      against LFA-1. This led to a 27-fold increase in the number of muscle fibers
      expressing a reporter gene present in the donor myoblasts when the host is also
      adequately immunosuppressed with FK506. Therefore, both the nonspecific
      inflammatory reaction and the specific immune response should be adequately
      controlled following myoblast transplantation.

PMID- 9142442
TI  - Hybrid muscular tissues: preparation of skeletal muscle cell-incorporated
      collagen gels.
AB  - We prepared three different types of hybrid muscular tissues in which C2C12 cells
      (skeletal muscle myoblast cell line) were incorporated in type I collagen gels
      and then differentiated to myotubes upon culture: a disc-type, a polyester mesh
      reinforced sheet-type, and a tubular type. A cold mixed solution of the cells and
      type I collagen was poured into three different types of molds and was kept at 37
      degrees C in an incubator to form C2C12 cell-incorporated gels. A polyester mesh
      was incorporated into a gel to form the sheet-type tissue. The tubular hybrid
      tissue was prepared by pouring a mixed solution into the interstitial space of a
      tubular mold consisting of an outer sheath and a mandrel and subsequently
      culturing after removal of the outer sheath. Hybrid tissues were incubated in a
      growth medium (20% fetal bovine serum medium) for the first 4 days and then in a
      differentiation medium (2% horse serum medium) to induce formation of myotubes.
      Transparent fragile gels shrank with time to form opaque gels, irrespective of
      type, resulting in the formation of quite dense hybrid tissues. On day 14 of
      incubation, myoblasts fused and differentiated to form multinucleated myotubes.
      For a tubular type hybrid tissue, both cells and collagen fiber bundles became
      circumferentially oriented with incubation time. Periodic mechanical stress
      loading to a mesh-reinforced hybrid tissue accelerated the cellular orientation
      along the axis of the stretch. The potential applications for use as living
      tissue substitutes in damaged and diseased skeletal and cardiac muscle and as
      vascular grafts are discussed.

PMID- 9142443
TI  - Immunological response against allogeneic chondrocytes transplanted into joint
      surface defects in rats.
AB  - Rat chondrocytes isolated from the articular-epiphyseal cartilage complex were
      transplanted into defects prepared in articular cartilage and subchondral bone.
      Transplants were taken for examination after 3 and 8 wk. Cartilage formed by
      syngeneic chondrocytes did not evoke formation of infiltrations. Contrary to
      that, in the vicinity of cartilage produced by allogeneic chondrocytes numerous
      infiltrating cells were present and cartilage resorption could be observed.
      Cyclosporine-A (CsA) treatment of recipients of allogeneic chondrocytes only
      partially suppressed accumulation of infiltrating cells and matrix resorption.
      Antichondrocyte immune response of chondrocyte graft recipients was studied by
      evaluation of spleen mononuclear cells (SMC) stimulation in mixed splenocyte
      chondrocyte cultures and by evaluation of antichondrocyte cytotoxic antibodies.
      No difference in stimulation of SMC from intact rats by syngeneic and allogeneic
      chondrocytes was observed. Stimulation by allogeneic chondrocytes was slightly
      but significantly higher in recipients of syngeneic grafts. SMC of allogenic
      chondrocyte recipients were strongly stimulated by allogeneic chondrocytes. This
      response was absent in recipients treated with CsA. Spontaneous antichondrocyte
      cytotoxic antibody activity was detected in intact rats and in recipients of
      syngeneic grafts. In recipients of allogeneic chondrocytes the antibody response
      against allogeneic chondrocytes was raised but was statistically not significant
      owing to the considerable variation in the level of spontaneously occurring
      antichondrocyte antibodies.

PMID- 9142444
TI  - Culture expanded canine mesenchymal stem cells possess osteochondrogenic
      potential in vivo and in vitro.
AB  - Mesenchymal Stem Cells (MSCs) possessing the capacity to differentiate into
      various cell types such as osteoblasts, chondrocytes, myoblasts, and adipocytes
      have been previously isolated from the marrow and periosteum of human, murine,
      lapine, and avian species. This study documents the existence of similar
      multipotential stem cells in canine marrow. The cells were isolated from marrow
      aspirates using a modification of techniques previously established for human
      MSCs (hMSCs), and found to possess similar growth and morphological
      characteristics, as well as osteochondrogenic potential in vivo and in vitro. On
      the basis of these results, the multipotential cells that were isolated and
      culture expanded are considered to be canine MSCs (cMSCs). The occurrence of
      cMSCs in the marrow was determined to be one per 2.5 x 10(4) nucleated cells.
      After enrichment of the cMSCs by centrifugation on a Percoll cushion, the cells
      were cultivated in selected lots of serum. Like the hMSCs, cMSCs grew as colonies
      in primary culture and on replating, grew as a monolayer culture with very
      uniform spindle morphology. The population doubling time for these cMSCs was
      approximately 2 days. The morphology and the growth kinetics of the cMSCs were
      retained following repeated passaging. The osteogenic phenotype could be induced
      in the cMSC cultures by the addition of a synthetic glucocorticoid,
      dexamethasone. In these osteogenic cultures, alkaline phosphatase activity was
      elevated up to 10-fold, and mineralized matrix production was evident. When cMSCs
      were loaded onto porous ceramics and implanted in autologous canine or athymic
      murine hosts, copious amounts of bone and cartilage were formed in the pores of
      the implants. The MSC-mediated osteogenesis obtained by the implantation of the
      various MSC-loaded matrix combinations is the first evidence of osteogenesis in a
      canine model by implantation of culture expanded autologous stem cells. The
      identification and isolation of cMSCs now makes it feasible to pursue preclinical
      models of bone and cartilage regeneration in canine hosts.

PMID- 9142446
TI  - Cell proliferation in retinal transplants.
AB  - The MIB-1 antibody against a nuclear protein Ki-67 was used to study the
      proliferation of cells in the rabbit retinal transplants. Fragmented pieces of
      embryonic day 15 rabbit retinas were transplanted into the subretinal space of
      adult rabbits and allowed to survive for different times. Fragmented donor tissue
      starts organizing in rosettes 1 day after transplantation. The transplanted cells
      continue to proliferate in the host eye and their pattern of proliferation
      resembles that of normal developing retina, suggesting that the factors
      responsible for the proliferation pattern are preserved after transplantation.
      The dividing cells in metaphase line up in the luminal layers of the rosettes.
      Certain cells become postmitotic in the regions corresponding to the inner retina
      first, followed by the cells in the luminal layers of rosettes. Cells in the
      regions between the rosettes, corresponding to the inner nuclear layer,
      presumably the Muller cells, proliferate significantly for the equivalent age of
      postnatal day 2. Few cells in these regions proliferate for at least the
      equivalent age of postnatal day 11 in transplants. There is a layer of
      nonproliferating, degenerating cells in the transplant situated close to the host
      retina. However, some cells in this layer, situated at the host-graft interface,
      proliferate. These cells proliferate for a long time possibly indicating gliosis.

PMID- 9142445
TI  - Metabolic energy capacity of dopaminergic grafts and the implanted striatum in
      parkinsonian nonhuman primates as visualized with cytochrome oxidase
      histochemistry.
AB  - Histochemistry for visualization of the mitochondrial enzyme cytochrome oxidase
      has been detect cellular and regional differences in brain metabolism. We have
      examined the pattern of cytochrome oxidase (CO) staining in grafts of embryonic
      ventral mesencephalic tissue, and in the implanted striatum, of MPTP-treated
      monkeys as one index of the functional activity of grafted tissue and its
      influence on the host brain. Four monkeys were selected for study based on
      interesting variations in dopamine (DA) neuron content of their bilateral grafts
      as demonstrated with tyrosine-hydroxylase (TH) immunocytochemistry. The results
      suggest that grafts rich in DA neurons increase the metabolic activity of the
      implanted striatum of DA-depleted monkeys, and that this improvement of local
      energy metabolism is greater in the vicinity of grafts containing greater numbers
      of DA neurons. In addition, the pattern of CO staining within tissue transplants
      indicates that DA neurons exhibit the highest rate of metabolic activity among
      all cell types contained in the ventral mesencephalic grafts, and that the
      transplants receive metabolically active innervation from outside or within the
      grafted tissue.

PMID- 9142447
TI  - Transplantation of retinal pigment epithelium using viable cryopreserved cells.
AB  - Transplantation of retinal pigment epithelium (RPE) may have potential clinical
      application for the surgical treatment of RPE-specific retinal degeneration,
      including age-related macular degeneration. The feasibility of an RPE storage
      bank has been investigated by experimenting with transplantation using viable,
      cryopreserved RPE cells. Fresh and cultured fetal human and bovine RPE cells were
      cryopreserved in 90% fetal bovine serum containing 10% dimethyl sulfoxide. The
      viability of the cells before and after cryopreservation was evaluated by trypan
      blue dye exclusion test, microculture tetrazolium assay (MTA), tissue culture,
      and transplantation after cryopreservation. The origin of RPE cells before and
      after cryopreservation was assessed by immunocytochemistry, immunoblotting, and
      indirect ELISA of RPE-marker protein using cytokeratin for cultured fetal human
      RPE cells and by immunocytochemistry of cellular retinaldehyde-binding protein
      (CR-ALBP) for cultured bovine RPE cells. Freshly isolated and cryopreserved
      uncultured bovine RPE cells were transplanted by posterior transscleral approach
      into the subretinal spaces of adult albino rabbits and 23-day-old Royal College
      of Surgeons (RCS) rats with a 33 gauge Hamilton syringe. Following surgery,
      artificial retinal blebs were confirmed by fundus examination. Morphologic
      examination was performed postoperatively by light and electron microscopy in
      albino rabbits and by light microscopy in RCS rats up to 3 mo. Control subretinal
      injections using vehicle solution also were performed in RCS rats. Cultured fetal
      human and bovine RPE cells after cryopreservation were found to be viable, based
      on the results of trypan blue dye exclusion test, MTA, tissue culture, and
      transplantation. Expression and reexpression of cytokeratin intermediate
      filaments in cultured fetal human RPE were demonstrated by immunocytochemistry,
      immunoblotting, and indirect ELISA before and after cryopreservation.
      Immunocytochemistry of CRALBP before and after cryopreservation in uncultured
      bovine RPE cells disclosed expression and reexpression of RPE cell marker
      protein. No uncultured fetal human RPE cells showed proliferation in tissue
      culture after cryopreservation. In rabbits, light and electron microscopy
      disclosed xenografted RPE cells residing on Bruch's membrane of the host retina.
      No sign of graft vs. host reaction was observed. No morphologic difference was
      noted between the fresh and 10-day-old cryopreserved RPE cells in situ following
      transplantation at day 25. In RCS rats, subretinal injection of 3-wk-old
      cryopreserved bovine RPE cells partially rescued photoreceptor cells locally at
      the transplanted area observed at 3 mo postoperatively. The retinal
      photoreceptors at the inferior hemisphere of the transplanted eye and the eye
      injected with vehicle solution showed no rescue effect. We found that
      cryopreserved cultured fetal human RPE cells and uncultured and cultured bovine
      RPE cells can be used for RPE transplantation studies. The ability to create an
      RPE storage bank as a source of donor cells may result in several clinical
      advantages.

PMID- 9142448
TI  - Comparison of methods used for the removal of DMSO following cryopreservation and
      the development of an automated protocol.
AB  - Current methods of islet isolation are limited, thus requiring islets to be
      pooled from multiple donors to provide sufficient islet mass to permit insulin
      independence following islet transplantation. Low temperature banking is one
      approach used to pool islet preparations. Recently, we developed a method for
      bulk cryopreservation of islets in a single freezer bag system that is less labor
      intensive and more readily kept sterile. As a further improvement to this bulk
      cryopreservation protocol we examined islet survival following slow-step dilution
      or our standard sucrose dilution protocol. Known numbers of canine islets were
      cryopreserved in DMSO by slow cooling to -40 degrees C, storing at -196 degrees
      C, and rapid thawing. When islets were frozen and thawed in glass tubes the
      recovery of islets after 48 h of tissue culture was significantly higher when the
      DMSO was removed using either a slow step (71.7 +/- 2.7%) or a modified slow step
      (75.7 +/- 3.9%) protocol as compared with the standard sucrose dilution protocol
      (65.7 +/- 3.0%) (p < 0.05, unpaired t-test). Insulin secretion in vitro and in
      vivo graft function was similar between the experimental groups. Similarly, when
      islets were frozen then thawed in freezer bags, islet recovery following 48 h
      postcryopreservation tissue culture at 37 degrees C was 74.8 +/- 2.4% for slow
      step dilution compared with 66.2 +/- 2.7% for the standard sucrose dilution group
      (p < 0.05, unpaired t-test). Islets thawed in the freezer bag using the modified
      slow-step dilution protocol showed equivalent functional viability during static
      incubation to nonfrozen controls. Bulk cryopreservation of isolated islets in
      single blood freezer bags is a practical alternative to cryopreservation in glass
      tubes. Development of an automated protocol for the slow stepwise removal of the
      cryoprotectant from islets in freezer bags will facilitate low temperature tissue
      banking of islets.

PMID- 9142449
TI  - Freezing characteristics of isolated pig and human hepatocytes.
AB  - The cellular response of isolated hepatocytes from pigs, humans, and human
      hepatoblastoma cells to freezing was characterized using cryomicroscopy and
      analyzed using a thermodynamic model for water transport and Intracellular Ice
      Formation (IIF). The value for the reference permeability, Lpg, was found to be
      5.8(10)-13, 1.62(10)-13, and 2.7(10)-14 m/Ns for pig, human, and Hep G2/C3A
      cells, respectively. The activation energy, Elp, was found to be 480 kJ/mol for
      pig hepatocytes, 216 kJ/mol for human, and 121 kJ/mol for Hep G2/C3A cells. The
      average temperature at which IIF (T(avg)IIF) occurs was calculated to be -7.24 +/
      2.3 degrees C for pig hepatocytes, -8.5 +/- 2.6 degrees C for human hepatocytes,
      and -9.6 +/- 4.5 degrees C for Hep G2/C3A cells. These results indicate that the
      freezing characteristics of pig and human cells are distinct and that the
      specific freezing characteristics need to be understood for the development of
      appropriate freezing protocols.

PMID- 9142450
TI  - Post-thaw viability and functionality of cryopreserved rat fetal brain cells
      cocultured with Sertoli cells.
AB  - Testis-derived Sertoli cells have been used to create an immune "privileged" site
      outside of the testis to facilitate cell transplantation protocols for diabetes
      and neurodegenerative diseases. In addition to secreting immunoprotective
      factors, Sertoli cells also secrete growth and trophic factors that appear to
      enhance the posttransplantation viability of isolated cells and, likewise, the
      postthaw viability of isolated, cryopreserved cells. It would be beneficial if
      Sertoli cells could be cryopreserved with the transplantable cell type without
      deleterious effects on the cells. This report describes a protocol for the
      cocryopreservation of rat Sertoli cells with rat ventral mesencephalic neurons,
      neurons from the lateral and medial ganglionic eminences and the hNT neuron cell
      line, and reports on the effects of Sertoli cells on the the postthaw viability
      of these neurons. Results of trypan blue exclusion analysis indicated that the
      presence of Sertoli cells did not deleteriously effect cryopreserved neurons and
      may improve their postthaw recoverability and viability in general. Specifically,
      results of the tyrosine hydroxylase immunostaining showed that Sertoli cells
      significantly enhance the postthaw viability of ventral mesencephalic
      dopaminergic cells in vitro.

PMID- 9142451
TI  - The testis-derived cultured Sertoli cell as a natural Fas-L secreting cell for
      immunosuppressive cellular therapy.

PMID- 9142453
TI  - Collagenase and human islet isolation.

PMID- 9142452
TI  - Meeting of the Cell Transplantation Society in Miami.

PMID- 9142454
TI  - Antibacterial activities of tosufloxacin against anaerobic bacteria and the
      electron micrograph of its bactericidal effects.
AB  - Tosufloxacin, a quinolone, showed a broad antibacterial spectrum against gram
      positive and gram-negative bacteria including anaerobic bacteria. Tosufloxacin
      was 4- to 8-fold more active than levofloxacin and ciprofloxacin. The MIC90 of
      tosufloxacin for clinical isolates of Bacteroides fragilis, Bacteroides vulgatus,
      Bacteroides thetaiotaomicron and Peptostreptococcus asaccharolyticus were 0.78,
      0.39, 1.56 and 0.39 micrograms/ml, respectively. Morphological observation with
      the scanning and transmission electron microscope revealed that exposure of B.
      fragilis ATCC 25285 to tosufloxacin resulted in the formation of filamentous
      cells with mesosome-like structures. Tosufloxacin also induced the mini-cell
      resulting from the unusual cell division system and a number of holes in the
      outer membrane. Tosufloxacin at 4 MIC caused some change in cell wall
      organization and cell lysis. After exposure of P. asaccharolyticus ATCC 14953 to
      tosufloxacin, the cells increased considerably in size and the cell wall and
      cross wall thickening was observed.

PMID- 9142455
TI  - Susceptibility of Moraxella catarrhalis to 21 antimicrobial drugs: validity of
      current NCCLS criteria for the interpretation of agar disk diffusion
      antibiograms.
AB  - Ninety-four clinical isolates of Moraxella catarrhalis were examined for
      susceptibility to 21 antimicrobial drugs; 67 isolates (= 71.3%) produced beta
      lactamase(s). In terms of antibiotic resistance, the number of isolates resistant
      to penicillin G, ampicillin, and cotrimoxazole were 56, 32, and 1, respectively.
      The number of isolates with intermediate susceptibility to penicillin G,
      ampicillin, ciprofloxacin, ofloxacin, cotrimoxazole, and fosfomycin were 11, 34,
      1, 2, 2, and 47, respectively. All 94 isolates proved susceptible to ampicillin +
      10 micrograms/ml of sulbactam, amoxicillin + 4 micrograms/ml of clavulanic acid,
      cefuroxime, cefotaxime, cefepime, cefepime, cefixime, imipenem, meropenem,
      chloramphenicol, doxycycline, tetracycline, fusidic acid, erythromycin,
      clarithromycin, and rifampin, as based on currently valid NCCLS criteria, where
      applicable. There were no very major or major discrepancies between agar dilution
      and agar disk diffusion test results. There were only a few minor discrepancies
      between test results, specifically: penicillin G (category IV = 4, category VI =
      1); ampicillin (category IV = 4, category V = 1, category VI = 7), amoxicillin +
      clavulanic acid (category III = 11), cotrimoxazole (category IV = 1, category V =
      1, category VI = 1), ciprofloxacin (category V = 1), and ofloxacin (category VI =
      2). The sole exception was fosfomycin, with a total of 25 minor discrepancies
      encountered (category III = 14, category V = 9, category VI = 2). Wilkins
      Chalgren agar compared favorably with Mueller-Hinton agar following examination
      with 11 selected antimicrobial drugs against 31 representative isolates of M.
      catarrhalis.

PMID- 9142456
TI  - Susceptibilities of 55 strains of Neisseria meningitidis isolated in Spain in
      1993 and 1994.
AB  - The in vitro susceptibility of 55 strains of Neisseria meningitidis isolated in
      1993 and 1994 at the Valme and Macarena Hospitals, Sevilla, Spain to penicillin,
      ampicillin, cefotaxime, cefpodoxime, imipenem, rifampin, ciprofloxacin,
      chloramphenicol, tetracycline, erythromycin and trimethoprim-sulfamethoxazole
      were determined by a microdilution method in Mueller-Hinton broth. Among our N.
      meningitidis isolates, 36.4% were found to be moderately resistant to penicillin,
      43.6% were resistant to trimethoprim/sulfamethoxazole. All the strains were
      susceptible to tetracycline, ciprofloxacin, cefotaxime and rifampin.

PMID- 9142457
TI  - Superior effect of tazobactam/piperacillin compared to piperacillin on beta
      lactamase-producing Pseudomonas aeruginosa.
AB  - To evaluate the synergistic antimicrobial effects of tazobactam (TAZ), a beta
      lactamase inhibitor, and piperacillin (PIPC) on Pseudomonas aeruginosa, we
      compared the antimicrobial effects of TAZ/PIPC with those of PIPC alone on
      bacteria inducibly or constitutively producing beta-lactamase. TAZ/PIPC had more
      potent antimicrobial effects compared with PIPC on clinical isolates producing
      beta-lactamase. In the treatment of mouse systemic infection, the therapeutic
      effect of PIPC was markedly decreased by beta-lactamase, but that of TAZ/PIPC was
      only slightly decreased. In the treatment of local infections in mice, the
      therapeutic effects of PIPC were decreased due to the induction of beta-lactamase
      and the emergence of bacterial strains constitutively producing beta-lactamase,
      while those of TAZ/ PIPC were not affected.

PMID- 9142458
TI  - Increase in high resistance to penicillin of clinical isolates of Streptococcus
      pneumoniae in Cadiz, Spain.
AB  - The aim was to determine the increase and present standing of penicillin
      resistant Streptococcus pneumoniae in Cadiz, Spain. We have studied
      retrospectively a total of 385 strains of S. pneumoniae obtained during the years
      1991, 1993 and 1995. Strains tested were isolated from clinical samples of
      patients attended at the University Hospital Puerta del Mar of Cadiz, Spain. The
      resistance rate to penicillin was 71.2% (47.0% in 1991, 72.8% in 1993 and 89.3%
      in 1995). The percentage of strains with high resistance was 51.4%. The increase
      was from 29.4% in 1991 to 75.2% in 1995. The incidence of penicillin-resistant
      pneumococci was more marked in nasopharyngeal carrier children (75.8%) than in
      invasive strains (30.2%). The increase in high resistance to penicillin in
      clinical isolates of S. pneumoniae is very pronounced in Cadiz, Spain.

PMID- 9142459
TI  - In vitro antitumor and antimicrobial activities of N-substituents of maleimide by
      adamantane and diamantane.
AB  - New N-1-adamantylcitraconimide (compound 1) and N-1-diamantylcitraconimide
      (compound 2) were synthesized by reaction of citraconic anhydride with 1
      aminoadamantane, and 1-aminodiamantane, respectively, followed by imidization
      with acetic anhydride and sodium acetate. Compound 1, N-1-adamantylmaleimide
      (compound 3) and N-1-diamantylmaleimide (compound 4) exhibited strong growth
      inhibitory activity against four cancer cell lines (Colo 205, Hep G2, SK-BR-3 and
      Molt-4). Moreover, compound 1 showed relatively specific cytotoxicity against the
      test tumor cell lines. Compound 2 exhibited growth inhibitory activity against
      Colo 205, and SK-BR-3 cells, similar to 5-fluorouracil. It was noted that
      compound 2 showed relatively low cytotoxicity against Molt-4 cells, approximately
      42 times lower than 5-fluorouracil. The N-substituents of imides with adamantly
      substituents have a more potent antitumor activity than the imides with diamantyl
      substituents. The imides with methyl substituents (compounds 1 and 2) showed
      relatively higher selectivity against the tested cancer cell lines than the
      imides without methyl substituents (compounds 3 and 4). Compounds 3 and 4 show
      good in vitro activities against Staphylococcus aureus and Trichophyton
      mentagrophytes. Compound 1 had weak antimicrobial activity against T.
      mentagrophytes.

PMID- 9142460
TI  - Effects of rokitamycin on phagocytosis and release of oxidant radicals of human
      polymorphonuclear leukocytes.
AB  - A rational choice of an antimicrobial agent must take into account not only the
      activity against the specific pathogen but also any possible negative or positive
      effects on the host defense system. Rokitamycin (RKM) is an orally active 16
      membered-ring macrolide; there are no reports of specific investigations of these
      activities in the literature. Polymorphonuclear neutrophils (PMNs) from healthy
      adult donors were incubated in medium alone or in medium containing increasing
      concentrations (1, 10, 50, 100 micrograms/ml) of RKM. In unwashed PMNs
      phagocytosis was unaffected by RKM, while luminol-amplified chemiluminescence
      (LACL) was significantly reduced by 50 and 100 micrograms/ml. When PMNs were
      washed after incubation phagocytosis was not modified but LACL was significantly
      restored. These characteristics of RKM were similar to those of roxithromycin and
      can be put in correlation with the cellular/extracellular ratio (30.5 for PMNs
      and 120 for macrophages) that was similar to that of roxithromycin but higher
      than of other macrolides. The molecular mechanisms by which high concentrations
      of these two macrolides produce such an impairment of LACL are still unclear. RKM
      has no unwanted effects on PMNs because the serum concentrations that can be
      obtained with the highest doses administered to man are lower than the
      concentrations which did not affect PMN functions in our study.

PMID- 9142461
TI  - Antifungal and immunoadjuvant properties of fluconazole in mice immunosuppressed
      with morphine.
AB  - We investigated the efficacy of fluconazole on experimental disseminated
      candidiasis in mice immunocompromised by chronic morphine treatment. CD1 mice
      were severely immunosuppressed by repeated morphine administrations, i.e.,
      subcutaneous (s.c.) injections of 75 mg/kg/day, 3 days before and 5 days after a
      systemic Candida albicans infection induced by intravenous administration of 1 x
      10(6) fungal cells/mouse. Fluconazole (2.5 mg/kg, s.c., at 6, 24 and 48 h
      postinfection) was very effective in prolonging survival time of morphine-treated
      mice. Fluconazole treatment also promotes a recovery of killing activity of
      polymorphonuclear leukocyte cells suppressed by morphine administrations.

PMID- 9142462
TI  - Protective effect of liposomal gentamicin against systemic acute murine
      brucellosis.
AB  - Liposomes of the stable multilamellar type, which previously demonstrated great
      efficiency in antibiotic transport [Vitas et al: Antimicrob Agents Chemother
      1996;40:146-151] were used in this study as carriers of gentamicin for treatment
      of mice lethally infected with Brucella abortus. Treatment with gentamicin in
      positively charged liposomes produced a protective effect when it was
      administered 1 day after lethal challenge (70% of protection). On the other hand,
      the use of free gentamicin or in liposomes with a negative net charge did not
      produce a protective effect. Moreover, the results reported here also indicated
      that cationic liposomes themselves had a therapeutic effect on the course of the
      infection (up to 50% of protection). In conclusion, we observed that cationic
      liposomal encapsulation of gentamicin resulted in an enhancement of the
      therapeutic activity of free gentamicin in this mouse model of acute infection.

PMID- 9142463
TI  - In vitro effect of natural and semi-synthetic carbohydrate polymers on Chlamydia
      trachomatis infection.
AB  - The effect of different natural and semi-synthetic polysaccharides on Chlamydia
      trachomatis multiplication in Hela 229 cells was evaluated. Some neutral,
      negatively and positively charged carbohydrates were able, in a dose-dependent
      fashion, to inhibit chlamydial infection by interfering mainly with the
      adsorption process. The inhibiting compounds, whose effect was shown within the
      concentration range of 8-200 micrograms/ml, were in order of action: dextran
      sulphate > glyloid sulphate 4327 > glycogen sulphate 4427 > arabic gum = glyloid
      > chitosan > glycogen. Data obtained suggested that antichlamydial activity was
      not only related to the electric charge of these molecules but could also be
      attributed to other features of their polymeric backbone. Since carbohydrate
      polymers have also been shown to inhibit the early stages of infection by viral
      agents causing sexually transmitted diseases, the employment of these molecules
      for prevention or treatment of mixed viral-C. trachomatis infections can be
      hypothesized.

PMID- 9142464
TI  - Clinical pharmacokinetics and therapeutic efficacy of ceftriaxone in Chinese
      adults.
AB  - The pharmacokinetics of ceftriaxone were studied in 5 healthy Chinese volunteers
      who received single doses of 1 or 2 g by intravenous infusion at 2-weekly
      intervals. Only 50 microliters of plasma was required for the determination of
      plasma ceftriaxone concentrations using an improved high-performance liquid
      chromatography method. The interday variation was less than 5% and the
      relationship between peak height ratio and concentration was linear over the
      range 1-500 micrograms/ml. The distribution of ceftriaxone best fitted a two
      compartment pharmacokinetic model, and the pharmacokinetic parameters were
      similar for the two doses. Furthermore, these pharmacokinetic parameters were
      similar in 20 adult Chinese patients who had received ceftriaxone, 1 g twice
      daily or 2 g once daily, for various severe bacterial infections. These
      parameters were, however, dependent on renal function. The rate of elimination
      and clearance of ceftriaxone were similar to the values reported for other
      nationalities. The therapeutic outcomes for patients receiving 1 g twice daily
      were two cures, three improvements and one failure, and for those receiving 2 g
      once daily, seven cures, four improvements and one failure. Once daily infusion
      of ceftriaxone therefore seems to be effective in the treatment of severe
      bacterial infections in Chinese patients.

PMID- 9142465
TI  - Rejuvenation of the upper face. A logical gamut of surgical options.
AB  - The prime objective of forehead rejuvenation is to correct the factors that
      accentuate the impression of aging, namely, eyebrow ptosis, glabella frown lines,
      forehead wrinkles, and asymmetry. Options for forehead rejuvenation are
      undergoing a renaissance. With the wide variety of choices currently available,
      accurate analysis of the presenting problem is mandatory so that the appropriate
      surgical technique can be chosen. The less invasive endoscopic procedures have a
      low morbidity rate and great patient satisfaction. Not all patients are
      candidates for these procedures, however. A thorough knowledge of alternative
      methods, including botulinum injection, fat injection, fat grafting, and
      subcutaneous approaches to the brow, are necessary if optimal aesthetic results
      are to be accomplished. Having an armamentarium of forehead rejuvenation
      techniques is, therefore, the key to individualizing treatment for each patient.

PMID- 9142466
TI  - Endoscopic facial rejuvenation.
AB  - The use of an endoscope is a reliable way to perform facial rejuvenation, to
      correct eyebrow imbalance, periorbital and malar soft-tissue sagginess, and soft
      tissue displacement in the lower face and neck. It allows great magnification and
      tissue dissection control while observing in situ tissue modification and the
      immediate results. In mild cases of brow ptosis without muscle hyperactivity,
      wide undermining and fixation can be a simple way to achieve a good result. When
      hyperactivity of the muscles is present with or without brow ptosis, a more
      complex procedure can be done, which requires the treatment of the appropriate
      musculatures. The result are comparable to those achieved with the open approach
      with the advantage of a shorter scar, minimal permanent numbness, and much better
      patient acceptability.

PMID- 9142467
TI  - The extended browlift.
AB  - The endoscopic extended browlift adds to the armamentarium against aging, serving
      as an excellent stand alone procedure in the younger patient in whom the lower
      face and neck are minimally affected. It accomplishes a repositioning of the
      orbital portion of the orbicularis oculi muscle thereby minimizing resection of
      eyelid skin, muscle, and fat. Its lift of the malar pad causes a pleasing
      transition onto the upper face blending nicely into the lower face. In more
      advanced aging, the extended browlift serves as a powerful adjunct to procedures
      on the eyelids, lower face, and neck. It corrects troublesome orbital festoons
      and malar bags and reduces the upper third of the nasolabial fold. Its transition
      effect in the lower face has allowed an alternative procedure with more limited
      SMAS-skin undermining to be performed in smokers. The primary disadvantage of the
      procedure is the necessity of thoroughly understanding and familiarizing oneself
      with the somewhat confusing temporal anatomy, the location of the retaining
      ligaments of the cheek, and the relationship of the facial nerve to the deep
      plane. A failure to recognize and release the retaining structures will limit
      significantly the outcome of the procedure. Careless or misdirected dissection
      over the zygomaticus major muscle may directly injure the muscle or the nerve
      branches to the orbicularis oculi muscle. Forty-two patients who underwent an
      endoscopic extended browlift now have been followed from 6 to 18 months. The
      patient representing the first endoscopic attempt had unilateral weakness of the
      forehead and bitemporal fat atrophy. The forehead weakness resolved at 4 weeks
      postoperatively. The temporal fat atrophy was corrected at 1 year postoperatively
      with micro fat grafts. A second patient done as a demonstration at another
      institute had forehead weakness and excessive tension on one side. The weakness
      and tension reportedly resolved at 3 months. No patients have had permanent
      weakness. The most frequent occurrence following the procedure was the return of
      brow asymmetry that was present before surgery. Attempts at correcting this
      preoperative finding were generally unsuccessful.

PMID- 9142468
TI  - A 15-year follow-up study of the non-SMAS skin-tightening facelift with midface
      defatting. Equal or better than deeper plane procedures in result, duration,
      safety, and patient satisfaction.
AB  - This article outlines the author's philosophy on facial aging that he uses in a
      surgical technique that is unique because it requires no SMAS tightening,
      incision above the auricle, deep-plane dissection, subperiosteal dissection, or
      stitches in the face above the mandibular border. The fatty nasolabial and
      labiomandibular prominences are excised using sharp dissection or curette to
      flatten these areas. Various case studies with extensive follow-up are provided.
      In the author's experience, this surgical technique has shorter recovery time,
      higher patient satisfaction, fewer complications, excellent longevity, and a more
      natural aesthetic result than deeper and more extensive techniques.

PMID- 9142469
TI  - Facelift. Planning and technique.
AB  - Experience has shown that a superior facelift result is not possible without
      modification of the SMAS, platysma, and other deep facial structures. Although
      techniques vary and a consensus of opinion is unlikely to emerge, any surgeon
      able to identify the anatomic basis of his or her patients' problems can, through
      the application of logic and careful planning, select appropriate methods that
      are safe, effective, and rational. Presented here is the author's technique,
      which has delivered satisfaction to many patients.

PMID- 9142470
TI  - The endo-facelift. Basics and options.
AB  - This article presents our approach to performing an endoscopically assisted
      facelift. The advantages of the subperiosteal dissection are discussed. The
      procedure is expoused considering different approaches and variations depending
      on each particular case. Surgical procedures for the forehead, cheeks, and neck
      are discussed separately. Each procedure considers key maneuvers to liberate and
      relocate the deep soft tissues; for example, the transpalpebral approach to the
      forehead, the transpalpebral approach to the centrofacial area, and the
      subperiosteal mandibular dissection. Indications, limitations, and some advice to
      avoid complications also were presented.

PMID- 9142471
TI  - Direct fixation of the malar pad.
AB  - In most patients, the upper portion of the subcutaneous fatty mass--the malar pad
      -is modest in size and only moderately displaced inferiorly. Mobilization of the
      malar pad together with the ovelying skin flap achieves a pleasing result in
      these cases. Occasionally a patient will present with very prominent and ptotic
      malar fat pads and deep nasolabial folds that cannot be adequately addressed by
      existing methods. This article describes a technique of malar pad suspension by
      direct suturing that preserves the blood supply to the pad while placing it in a
      higher, more aesthetic position.

PMID- 9142472
TI  - Composite rhytidectomy. Finesse and refinements in technique.
AB  - These points of refinement in flap dissection and closure may be helpful to
      surgeons who perform composite rhytidectomy. My experience in the past 6 years of
      doing exclusively composite facelifts is that there is consistent improvement in
      results with shorter and shorter convalescent times after using these
      refinements. When a primary rhytidectomy is performed, repositioning of all the
      deep elements of the aging face is necessary to maintain harmony in facial
      rejuvenation (Fig. 9). Composite rhytidectomy is of enormous benefit in secondary
      rhytidectomy (Fig. 10) when the surgeon's goal must be to regain harmony, which
      frequently is lost following conventional rejuvenative procedures.

PMID- 9142473
TI  - Facial recontouring with lipostructure.
AB  - Lipostructure is a natural, long-lasting method of filling and supporting the
      face using intricate layering of infiltrated autologous tissue. This method
      allows the tissues to be sculpted to enact three-dimensional augmentation of
      facial elements. Because the grafted fat becomes integrated into the host
      tissues, it is almost undetectable after transplantation, except by photography.
      To successfully use fatty tissue as such a graft, attention must be paid to the
      nature of fatty tissue; to the methods of harvesting, transfer, and placement;
      and to the preparation of the patient. Fatty tissue is a complex, delicate
      structure that is easily damaged by mechanical and chemical insults. Successful
      fat transplantation demands that every step be practiced with attention to this
      fragile nature of fatty tissue. Precision is an important consideration in the
      augmentation of millimeters of facial elements. The true volume of infiltration
      is difficult to judge if too much blood, lidocaine, or oil is present in the
      tissue being placed. Fat is living tissue that must be in close proximity to a
      nutritional and respiratory source to survive. Therefore, placement of small
      amounts of fatty tissue in multiple tunnels assumes the utmost importance in the
      quest for both survival of fatty tissue and an aesthetically appropriate
      correction. Successful, three-dimensional sculpting requires attention to patient
      preparation, meticulous planning, and fastidious photographic evaluation. The
      potential applications in aesthetic and reconstructive surgeries of this new tool
      are profound. Lipostructure represents an important advance in plastic surgery: a
      safe, long-lasting method of recontouring the face with autologous tissue.

PMID- 9142474
TI  - Therapeutic skin care in the mature patient.
AB  - New understanding regarding the pathophysiology of intrinsically and
      extrinsically aged skin has allowed the development of topical medications
      designed to optimize skin appearance. Further research undoubtedly will yield
      more biologically active substances of value in the mature patient.

PMID- 9142475
TI  - Aesthetic skin resurfacing with the high-energy ultrapulsed CO2 laser.
AB  - CO2 laser resurfacing, using the new generation high-energy output pulsed lasers,
      provides a highly accurate method of resurfacing and rejuvenating facial skin.
      Its applications are widespread and well accepted by the general population
      (Color Figs. 3 to 8). Complications may occur, which may be minimized through
      adequate laser training and appreciation of the mechanisms of skin healing.

PMID- 9142476
TI  - A peeler's thoughts on skin improvement with chemical peels and laser
      resurfacing.
AB  - The new pulsed CO2 lasers are an exciting modality. They have the ability to do
      what no other procedure can do with the same safety profile. The drawbacks of
      cost, pain and prolonged healing, however, serve to limit the lasers use to a
      niche, rather than replacing all other means of skin resurfacing. Skin problems
      of the epidermis and superficial papillary dermis are more easily and less
      expensively treated with chemical peeling. This includes most types of
      hyperpigmentation as well as actinic keratoses and poorly textured skin. This is
      especially true of postinflammatory hyperpigmentation, in which any procedure
      that creates prolonged erythema dramatically increases the risk of increased
      pigmentation. In these patients, the use of CO2 laser resurfacing is risky, if
      not even contraindicated. Skin problems of the deeper papillary dermis and
      reticular dermis, such as rhytides and scars, however, respond as well to laser
      resurfacing as they do to deep chemical peels, but with a better safety profile
      and a more natural clinical appearance of the healed skin. In many cases, the
      patient would be better served with a medium depth chemical peel of the entire
      face and laser resurfacing of the rhytides in the perioral or periorbital areas.
      This would give the patient the best clinical result with the fastest recovery.
      The major drawback to this type of therapy has been that the postoperative care
      of the two treatment regions is different. This may cause some logistical
      difficulties for the patient, as well as some confusion. Certainly, another
      option is to treat the patient on two separate occasions; that is, first peel the
      entire face and then later go back and laser resurface the areas of the remaining
      rhytides. Although this approach creates more healing time for the patient, it
      minimizes the areas of prolonged erythema, thereby allowing the patient a faster
      return to normal. As laser technology continues to advance, we can expect faster
      healing times and less expensive machinery. Presumably, with our current
      understanding of the wound healing process, we should expect better post laser
      treatment regimens, with associated faster healing. Therefore, it is distinctly
      possible that the current niche for pulsed CO2 lasers will be expanded greatly in
      the next year or two.

PMID- 9142477
TI  - History and examination of the orofacial pain patient.
AB  - The clinician should recognize the importance of screening examinations for all
      patients seen in the dental office. The elements of a brief screening history and
      examination have been reviewed. In addition, the indications and elements of a
      comprehensive history and examination have been described. A discussion of
      current opinion on available diagnostic testing was also presented.

PMID- 9142478
TI  - Orofacial pain mechanisms and their clinical application.
AB  - This article has discussed the peripheral and central mechanisms of the various
      orofacial pain conditions, including musculoskeletal disorders, neurogenic
      inflammation, and neuropathic pain. To make an accurate diagnosis of orofacial
      pain and render treatment, all organ systems need to be considered and evaluated.
      Central sensitization was discussed as it relates to musculoskeletal disorders
      and neuropathic pain. It has been suggested that treatment of these disorders be
      problem oriented, addressing both peripheral and central mechanisms if present.
      Musculoskeletal disorders are characterized by pain that is provokable with
      function and manipulation. Neurovascular pain is episodic with pain-free periods
      between attacks. The pain is not related to or provoked by jaw function.
      Neuropathic pain is more continuous and may be aggravated by light touch.
      Neuropathy with peripheral involvement responds variably to local anesthetics but
      may need to be treated with topical or local agents as well as centrally acting
      agents. Neuropathic pain that does not respond to topical or local agents is more
      profoundly centralized. These conditions need to be treated with centrally acting
      agents. In addition, if there is no response to medications, sympathetic
      involvement needs to be ruled out with sympathetic ganglion blockade.

PMID- 9142479
TI  - Sleep disorders. Overview and relationship to orofacial pain.
AB  - Pain problems associated with the orofacial region need to be evaluated
      thoroughly. This article discusses the multiple approaches that may be necessary
      to gain the best result.

PMID- 9142480
TI  - Influences of dysfunctional respiratory mechanics on orofacial pain.
AB  - This article reviewed the anatomic issues of respiration and the active and
      passive mechanics of the thorax as related to dysfunctional breathing. Influences
      from respiratory dysfunction on forward head posture and temporomandibular
      dysfunction were offered. Discussion of inspiratory and expiratory muscle
      responsibilities, effects of diaphragmatic dystonia and abdominal weakness, and
      results of improper coordination and timing of respiratory muscle should all give
      the dentist and physical therapist an appreciation of the need for careful
      observation and appropriate treatment with the patient experiencing TMD and
      dysfunctional respiratory mechanics. Summaries of hyperinflation relationships
      and treatment considerations should help in the management of TMD.

PMID- 9142481
TI  - An overview of bruxism and its management.
AB  - Bruxism is a mandibular parafunction and it can be regarded as a forcible
      clenching or grinding of the dentition or a combination of both. Because bruxist
      behavior can be exhibited during both waking and sleeping hours, neither aspect
      should be ignored by the practitioner as a potential contributing factor of
      disturbances of the masticatory system. This article provides a general overview
      of bruxism relative to epidemiology, etiology, characteristics, diagnosis, and
      management.

PMID- 9142482
TI  - Differentiation of orofacial pain related to Lyme disease from other dental and
      facial pain disorders.
AB  - The diagnostic process for the orofacial pain patient is often perplexing.
      Compounding the process of solving a diagnostic mystery is the multiplicity of
      etiologic factors. The propensity for Lyme disease to present with symptoms
      mimicking dental and temporomandibular disorders makes the task even more
      complex. It is hoped that the reader is cognizant of the fact that a pathologic
      process of dental structures--the teeth and their attachments to the mandible and
      maxilla, the temporomandibular joints, masticatory musculature, and vascular
      supply and sensory innervation of the oromandibular anatomy--may also be the
      source of facial pain. Although unique, similar complaints may also be
      manifestations of other causes, including pain associated with Lyme disease. The
      informed and fastidious clinician does not overlook these possibilities when
      evaluating the headache and facial pain patient. The clinician should be equipped
      with the knowledge and minimal armamentarium to evaluate the patient
      appropriately. To paraphrase from Sherlock Holmes, we must first eliminate the
      impossible, whatever is left is the truth, no matter how unlikely. A differential
      diagnosis must be achieved based on clinical experience, unbiased observations,
      and probability.

PMID- 9142483
TI  - Pharmacotherapeutics in the management of orofacial pain.
AB  - Pharmacotherapy is a cornerstone in the treatment of pain. Medications are often
      used to assist in diagnosis of the pain problem because positive or negative
      responses may delineate the cause of a particular pain. Through rational drug
      prescribing habits and education of both patients and physicians, effective
      regimens can be designed to increase pain control while decreasing untoward drug
      side effects.

PMID- 9142484
TI  - Psychoneuroimmunology and its relationship to the differential diagnosis of
      temporomandibular disorders.
AB  - Psychoneuroimmunology (PNI) is a field of medicine which joins immunology and
      neurobiology. It focuses on the relationship of stress upon the hypothalamic
      adrenal-pituitary (HPA) axis. Depletion of hormones and neurotransmitters within
      the HPA-axis, as a result of stress, can lead to a multitude of diseases and
      disorders. Therefore, it is necessary for the dentist to be familiar with PNI and
      the HPA-axis in order to make an accurate diagnosis of TMD.

PMID- 9142485
TI  - Managed health care and orofacial pain.
AB  - Dental and insurance communities must find common ground to manage orofacial pain
      effectively. By screening patients with orofacial pain for earlier referral, the
      incidence of improper medical utilization and the potential for chronic pain may
      be reduced.

PMID- 9142486
TI  - Intraoral orthotic therapy.
AB  - Despite the unanswered questions on the physiologic mechanisms that explain the
      effectiveness of intraoral orthotics on reducing symptoms of TMD, there is still
      a plethora of documentation that intraoral orthotics, when appropriately used in
      the management plan, can contribute to the relief of TMD symptoms. The clinician
      is encouraged to evaluate fully each particular patient case in an effort to
      develop a differential diagnosis that leads to an effective management plan,
      which, in turn, addresses the cause(s) as best as possible. Before commencing any
      intraoral orthotic therapy for a TMD, the clinician should be confident that the
      patient will benefit from the therapeutic approach to be employed or, at least,
      that the resultant effect, or lack thereof, on the symptoms will provide
      additional diagnostic information. The clinician also needs to take into account
      that approximately 40% of patients suffering from TMD demonstrate a favorable
      response to intraoral orthotic therapy just from a placebo effect. As with any
      treatment, a good patient-dentist relationship concomitant with patient education
      can allay patient concerns and anxieties, which, in and of themselves, can
      contribute to a positive and favorable response to intraoral orthotic therapy.

PMID- 9142487
TI  - Special considerations in orofacial pain and headache.
AB  - The dental profession faces educational, scientific, and ethical challenges in
      orofacial pain and headache. Past educational deficiencies are being addressed
      with guidance and recommendations from the AADS, the ADA, and the AAOP. With
      education and further research, many dental ethical questions in TMD will be
      resolved. The educational process must continue with a solid foundation in
      scientific basis provided in university settings. The appropriate use of TMD
      diagnostic machines, treatment modalities, and management of perpetuating factors
      such as sleep will evolve with the new knowledge of scientific discovery. These
      are some of the many challenges of orofacial pain and headache disorders that
      warrant special consideration.

PMID- 9142488
TI  - Evaluation and management of maladaptive behaviors and psychological issues in
      temporomandibular disorder patients.
AB  - This article presents an overview of some of the behavioral and psychosocial
      issues involved in the care of TMJ and orofacial pain patients. The importance of
      a thorough pretreatment assessment is emphasized. Treatment options for oral
      habits, stress management, and other psychosocial challenges are briefly
      discussed.

PMID- 9142489
TI  - Cancer in the differential diagnosis of orofacial pain.
AB  - The clinician must maintain an awareness that at some time a patient may present
      in their busy dental practice with a chief concern of dental, sinus, or TMD-like
      pain that, in fact, is of cancer origin. The question remains if an earlier
      diagnosis can be established in cases similar to those illustrated. It is
      mandatory that a thorough medical and dental history be taken by all health care
      practitioners along with a systematic and comprehensive examination when
      addressing head and neck pain. This includes careful examination, including
      inspection and palpation, of the oral and extraoral structures and the cervical
      lymph nodes at regular intervals in all patients but especially in those who are
      at high risk. History of smoking and alcohol use is of particular concern. Early
      head and neck cancer is usually symptomatic. Persistence in applying this
      practice philosophy is imperative.

PMID- 9142490
TI  - Nonodontogenic toothache.
AB  - Toothache is a common complaint in the dental office. Most toothaches have their
      origin in the pulpal tissues or periodontal structures. These odontogenic pains
      are managed well and predictably by dental therapies. Nonodontogenic toothaches
      are often difficult to identify and can challenge the diagnostic ability of the
      clinician. The most important step toward proper management of toothache is to
      consider that the pain may not be of dental origin. Signs and symptoms suggestive
      of nonodontogenic toothache are as follows: 1. Inadequate local dental cause for
      the pain. 2. Stimulating, burning, nonpulsatile toothaches. 3. Constant,
      unremitting, nonvariable toothaches. 4. Persistent, recurrent toothaches over
      months or years. 5. Spontaneous multiple toothaches. 6. Local anesthetic blocking
      of the suspected tooth does not eliminate the pain. 7. Failure to respond to
      reasonable dental therapy of the tooth.

PMID- 9142491
TI  - Expression of the pair-rule gene odd Oz (odz) in imaginal tissues.
AB  - odd Oz (odz), the only pair-rule gene that does not encode a transcription
      factor, is expressed in every imaginal disc and imaginal tissue of Drosophila
      melanogaster, as assessed by immunocytochemical staining for the protein and by
      odz-enhancer trap line staining. The eye imaginal disc expresses odz at the
      morphogenetic furrow, in R7 photoreceptor cells, and in adepithelial cells.
      Genetic evidence indicates that odz is involved in furrow progression, and in R7
      cell RTK receptor tyrosine kinase signalling. Expression in the wing pouch
      appears in a complex pattern that displays a symmetry axis at the dorsal-ventral
      boundary. In other dorsal thoracic disc sites, Odz appears at specific points of
      prospective thoracic integument and prospective proximal structures of the wing
      and haltere. Expression in the leg and antennal discs is strongest in prospective
      proximal segments at sites homologous between these discs. In addition, odz
      appears in sensory mother cells (SMCs) in all of the above-mentioned discs. This
      recurrence indicates the general importance of odz in the development of the
      peripheral nervous system (PNS), which complements the finding that it is
      expressed in the CNS, with striking optic lobe staining. odz must be involved in
      cellular signalling in pleiotropic roles in varied pathway contexts.

PMID- 9142492
TI  - Neural crest-like cells originate from the spinal cord during tail regeneration
      in adult amphibian urodeles.
AB  - Using in vitro cell-marking experiments and transplantation in tail regenerates,
      we have recently shown (Benraiss et al., 1996) that clonal cells derived from
      adult newt spinal cord (SC) cultures could find suitable cues in blastemal
      mesenchyme to enable them to differentiate into melanocytes or Schwann cells.
      This led to the question of whether neural crest-like cell derivatives might
      emerge from the ependymal tube as tail regeneration proceeded. To address this
      question we used the biolistic method for in situ transfection of caudal SC
      cells. These cells were transfected with an alkaline phosphatase marker gene. The
      potentialities of transfected cell derivatives in tail regenerates were analyzed
      using histochemistry or immunohistochemistry. As early as eight days after
      transfection, labeled cells were detected in the regenerating SC and around its
      "terminal vesicle" (TV). Two to four weeks following transfection, most of the
      labeled cell derivatives could be identified either by dark granules as
      melanocytes or by galactocerebroside staining as Schwann cells. Electron
      microscopic investigations revealed the incompletely organized cytoarchitecture
      of the TV, suggesting that an exit of cells was possible at this level, at least
      from its "open" dorsal part. Furthermore, the localization of ciliated cells in
      the blastemal mesenchyme, especially around the TV, supported this view by
      suggesting that they might be ependymal cells detached from it. Our findings
      therefore led us to believe that in the newt, during tail regeneration, neural
      crest-like cells emerging from the TV could participate in the formation of the
      peripheral nervous system, especially by providing Schwann cells and melanocytes.

PMID- 9142493
TI  - The mouse Nkx2-3 homeodomain gene is expressed in gut mesenchyme during pre- and
      postnatal mouse development.
AB  - The Nkx homeodomain proteins are members of a growing family of known vertebrate
      transcription factors that are believed to play a role in cell type specification
      and/or maintenance of the differentiated phenotype. In this article we report on
      the identification and developmental expression pattern of the mouse Nkx2-3 gene.
      The gene is expressed primarily in gut mesoderm, dinstinct regions of the
      branchial arches, the tongue epithelium, and limited domains in the developing
      jaws, possibly including tooth anlagen. In contrast to the chicken and Xenopus
      genes, Nkx2-3 expression in the mouse was not observed in the developing heart or
      neural tube. Thus, although structurally related to chicken and Xenopus Nkx2-3,
      the mouse gene exhibits an overlapping but distinct expression pattern that may
      suggest the existence of additional family members, as yet unidentified, in
      vertebrate organisms.

PMID- 9142494
TI  - Differential expression of troponin C genes during tongue myogenesis.
AB  - Determination of muscle fiber type is related to the developmental stage of the
      tissue. Ordinarily the final distribution of fast and slow fibers in a muscle is
      determined postnatally. Tongue muscle, however, is composed solely of fast-twitch
      fibers that express only troponin C fast mRNA and fast (type II) myosin heavy
      chain (MHC) proteins in both the adult and the one-day-old mouse. The fiber-type
      determination of this muscle was examined during fetal development. Both troponin
      C fast and slow mRNAs were expressed at initial stages of tongue development at
      embryonic day 18. However, by embryonic day 16 the troponin C fast transcripts
      predominated. AT 17 days of embryonic development, TnC fast mRNA was 10 times
      more abundant than TnC slow, and at 18 days of development the TnC slow mRNA was
      barely detectable. The tongue muscle myotubes expressed fast, slow, and embryonic
      MHC isoforms during early embryonic development. At 18 days of gestation, the MHC
      isoform expressed by the majority of the myotubes was the fast isoform, whereas
      the slow isoform was present in very few fibers. RT-PCR analysis of the MHC
      transcripts present throughout tongue development demonstrated expression of the
      mdms or type IIx MHC in both late fetal and postnatal stages of development. In
      contrast, the type I/beta slow MHC mRNA was undetectable in the postnatal and
      adult tongue. The absence of TnC and MHC slow-isoform mRNAs in the newborn mouse
      tongue suggests that slow isoform genes become dominantly repressed with the TnC
      F and MHC type IIx genes remaining transcriptionally active, giving rise to an
      unusually homogeneous fast-twitch phenotype. The tongue muscle fibers acquire
      their specific adult-type fiber characteristics during fetal development rather
      than postnatally.

PMID- 9142495
TI  - Vertical induction of engrailed-2 and other region-specific markers in the early
      chick embryo.
AB  - We investigated the role of vertical signals in the regulation of Engrailed-2, a
      regionally restricted (mesencephalon/metencephalon) neuroectodermal marker, using
      epiblast grafted from prospective neuroectoderm or prospective trunk mesoderm at
      mid-stage 3 in the gastrulating chick embryo. Grafts that were isolated from the
      rostral (prospective neuroectodermal) epiblast and placed rostral to or at the
      future mesencephalon/metencephalon level, between the endoderm and epiblast of
      stage 3d to stage 8 host embryos, expressed Engrailed-2 after 24 hr in culture,
      whereas these same grafts failed to express this marker when placed at a more
      caudal level. Grafts from caudal = (prospective trunk mesodermal) epiblast, which
      would ordinarily not express Engrailed-2, also expressed this marker when placed
      at the mesencephalon/metencephalon level, and failed to express it when grafted
      more caudally. The expression of four other markers, L5, Fgf8, Wnt-1, and
      paraxis, were also evaluated. Collectively, our results show that regionally
      restricted vertical signals are capable of inducing neuroectoderm from naive
      tissue, and of patterning epiblast to express some but not all
      mesencephalon/metencephalon isthmus markers. Experiments using grafts taken from
      older embryos indicated that the competence of prospective neuroectoderm to
      become regionally patterned by vertical signals is gradually lost between stage
      3c and stage 7. Similarly, prospective mesoderm from the caudal epiblast becomes
      unable to respond to vertical, neural-inductive signals at these stages. These
      observations support a role for vertical signals in the induction and patterning
      of the neuroectoderm at gastrula and early neurula stages.

PMID- 9142496
TI  - The CRABP I gene contains two separable, redundant regulatory regions active in
      neural tissues in transgenic mouse embryos.
AB  - The CRABP I gene is expressed in a spatiotemporal pattern in neural and
      mesenchymal tissues at the onset of organogenesis. The neural pattern of CRABP I
      expression includes specific rhombomeres of the hindbrain, neural crest cells and
      their derivatives the optic stalk, and the central area of the neural retina. We
      have created transgenic mouse lines with CRABP I 5' and transcribed regions fused
      to the lacZ structural gene that recapitulate much of this neural pattern of
      expression. Sequences 5' of the transcription initiation site between -7.8 and 
      3.2 kb confer beta-galactosidase expression to specific rhombomeres, migrating
      neural crest cells, trigeminal ganglion, the optic stalk, and the neural retina.
      We have also defined a region located between exon 1 and exon 8 that confers a
      portion of this expression pattern, including the mesencephalic projections of
      the trigeminal ganglion, the inner layer of the neural retina, and the peripheral
      layer of the posterior hindbrain. CRABP I expression in mesenchyme appears to
      require sequences in addition to or outside of those examined here.

PMID- 9142497
TI  - Disruption of Msx-1 and Msx-2 reveals roles for these genes in craniofacial, eye,
      and axial development.
AB  - In mouse embryos, the muscle segment homeobox genes, Msx-1 and Msx-2 are
      expressed during critical stages of neural tube, neural crest, and craniofacial
      development, suggesting that these genes play important roles in organogenesis
      and cell differentiation. Although the patterns of expression are intriguing,
      little is known about the function of these genes in vertebrate embryonic
      development. Therefore, the expression of both genes, separately and together,
      was disrupted using antisense oligodeoxynucleotides and whole embryo culture
      techniques. Antisense attenuation of Msx-1 during early stages of neurulation
      produced hypoplasia of the maxillary, mandibular, and frontonasal prominences,
      eye anomalies, and somite and neural tube abnormalities. Eye defects consisted of
      enlarged optic vesicles, which may ultimately result in micropthalmia similar to
      that observed in Small eye mice homozygous for mutations in the Pax-6 gene.
      Histological sections and SEM analysis revealed a thinning of the neuroepithelium
      in the diencephalon and optic vesicle and mesenchymal deficiencies in the
      craniofacial region. Injections of Msx-2 antisense oligodeoxynucleotides produced
      similar malformations as those targeting Msx-1, with the exception that there was
      an increase in number and severity of neural tube and somite defects. Embryos
      injected with the combination of Msx-1 + Msx-2 antisense oligodeoxynucleotides
      showed no novel abnormalities, suggesting that the genes do not operate in a
      redundant manner.

PMID- 9142498
TI  - Trisomy eight in ES cells is a common potential problem in gene targeting and
      interferes with germ line transmission.
AB  - The ability to contribute to the germ line is the most important experimental
      feature of embryonic stem (ES) cells. Using ES cells, it is possible to introduce
      targeted mutations into any gene and to derive the corresponding mutant mice. A
      common problem with this technology is that the ES cells often lack or have only
      a low efficiency of germ line transmission. To address this issue, we examined
      the relationship between the growth rate and karyotype of ES cells, and their
      ability to contribute to the germ line. We found that chromosomal abnormalities
      occurred rather frequently in ES cells. Cells having an abnormal number of
      chromosomes, in particular trisomy 8, were found in three independently derived
      ES cell lines, and this abnormality conferred a selective growth advantage on
      these cells. Selection of abnormal cells led to depletion and eventual loss of
      normal ES cells during consecutive passages. In comparison with parental ES
      cells, ES cells with trisomy 8 contributed rarely to the germ line. This
      realization allowed us to select, based upon ES cell clone morphology, those
      clones with the highest probability of contributing to the germ line. This
      insight is of practical value for any given gene targeting experiment as it
      permits optimization of the rate of success without having to rely on more
      elaborate tests such as karyotyping individual clones prior to blastocyst
      injection.

PMID- 9142499
TI  - Contribution of retinoic acid receptor gamma to retinoid-induced craniofacial and
      axial defects.
AB  - Exogenous retinoic acid (RA) administered during mouse embryogenesis can alter
      the pattern of the axial skeleton during two developmental periods: an early
      window (7 to 8.5 days post-coitum; dpc) and a late window (9.5 to 11.5 dpc).
      Treatment during the early window results in vertebral homeotic transformations
      (predominantly posteriorizations) concomitant with rostral shifts in Hox gene
      expression, while treatment at the later window results in similar
      transformations without detectable alterations in Hox gene expression patterns.
      Mice null for retinoic acid receptor gamma (RAR gamma) exhibit axial defects,
      including homeosis of several vertebrae, therefore establishing a role for this
      receptor in normal axial specification RAR gamma null mutants are also completely
      resistant to RA-induced spina bifida, which occurs in wildtype embryos treated at
      8.5-9.0 dpc, suggesting that this receptor specifically transduces at least a
      subset of the teratogenic effects of retinoids. To further investigate the role
      of RAR gamma in RA-induced defects during the early and late windows of retinoid
      sensitive vertebral patterning, RAR gamma heterozygotes were intercrossed,
      pregnant females treated with vehicle or RA at 7.3, 10.5 or 11.5 dpc and full
      term fetuses assessed for skeletal defects. Relative to wildtype littermates, RAR
      gamma null mutants treated at 7.3 dpc were markedly resistant to RA-induced
      embryolethality, craniofacial malformations, and neural tube defects.
      Furthermore, while RAR gamma null mutants were modestly resistant to certain
      vertebral malformations elicited by RA treatment at 7.3, they exhibited more
      pronounced resistance following treatment at 10.5 and 11.5 dpc. Moreover, several
      of the vertebral defects inherent to the RAR gamma null phenotype were abolished
      by RA treatment specifically at 10.5 dpc, suggesting that RAR alpha and/or RAR
      beta isoforms may substitute for certain RAR gamma functions, and that RAR gamma
      may elicit its normal effects on vertebral morphogenesis at this developmental
      stage.

PMID- 9142500
TI  - Spina bifida occulta in homozygous Patch mouse embryos.
AB  - In normal embryos, mRNA encoding platelet-derived growth factor A (PDGF A) and
      the platelet-derived growth factor receptor alpha (PDGFR alpha) are found within
      and adjacent to the site of vertebral development, the sclerotome. These patterns
      of expression are consistent with PDGF action on the developing sclerotome and
      dermis. Homozygous Patch (Ph) mutant mouse embryos lack the receptor gene
      (Pdgfra) due to an extensive deletion at that locus. Consistent with the spatial
      pattern of Pdgfra expression, striking deformities are found in the spine and
      ribcage of Ph/Ph embryos. In particular, we show that late-gestation Ph/Ph
      embryos have occult spina bifida involving the entire spinal column. We have
      analyzed the progression of the axial defects in homozygous Patch embryos in
      detail. By late gestation it appears that the components of the vertebrae are
      present, yet the neural arches of the spine are misshapen. We propose that PDGF A
      is required for proper positioning of the neural arch condensation at all axial
      levels. Furthermore, since the neural tube appears to close normally, we suggest
      that spina bifida in the Ph homozygote is caused primarily by a somitic mesoderm
      abnormality rather than a neural tube defect.

PMID- 9142501
TI  - Expression and regulation of steroid 5 alpha-reductase in the genital tubercle of
      the fetal rat.
AB  - The genital tubercle is a bipotential anlage that can develop into a penis or a
      clitoris. Formation of the penis requires synthesis within the tubercle of the
      androgen dihydrotestosterone by steroid 5 alpha-reductase isozymes. Isozyme 1
      mRNA and protein were present in epithelial cells, whereas isozyme 2 transcripts
      were present in mesenchymal cells of developing genital tubercles from day 17,
      19, and 21 rat embryos. These expression patterns were observed in both
      uncommitted anlagen and in committed male or female structures. Androgens did not
      significantly influence levels of 5 alpha-reductase mRNAs or affect their
      cellular distributions. Together with genetic data, the results implicate the
      mesenchyme as the crucial cell type in formation of the male external genitalia.

PMID- 9142502
TI  - Tissue-specific expression of murine Nkx3.1 in the male urogenital system.
AB  - The molecular mechanisms involved in growth and morphogenesis of the mammalian
      urogenital system are largely undefined. In this study, we describe the cloning
      and characterization of a novel murine homeobox gene, Nkx3.1, which is expressed
      in the male urogenital system during late embryogenesis and adulthood. We show
      that Nkx3.1 encodes a 38 kDa homeoprotein that has DNA binding properties similar
      to those of other Nkx family members. By RNAse protection analysis, we
      demonstrate that Nkx3.1 is expressed in late-gestation embryos and adults by
      tissues of the male urogenital system, including the testis, seminal vesicle, and
      the prostate. In adult males, expression of Nkx3.1 in the prostate increases
      during sexual maturation, and is significantly reduced following castration,
      suggesting that androgens are required for maintenance of Nkx3.1 expression. In
      situ hybridization analysis of mid- and late-gestation male embryos shows that
      Nkx3.1 is expressed in the developing urogenital sinus, testis, and prostatic
      buds. In addition to its expression in the urogenital system, we also find that
      Nkx3.1 is expressed in the dorsal aorta and kidney. These results implicate
      Nkx3.1 in the growth and development of the prostate and/or other tissues of the
      male urogenital system, and suggest that Nkx3.1 may play a role in sexually
      dimorphic as well as non-sexually dimorphic organogenesis.

PMID- 9142503
TI  - Sensitizing properties of spectral lights in 4-month-old human infants.
AB  - Previous studies of infant attention, learning, and memory have revealed that
      certain stimulus properties may increase an infant's arousal or excitation level,
      thereby increasing responsiveness and facilitating the encoding and processing of
      information. In a series of experiments aimed at identifying stimulus
      determinants of sensitization, we examined visual responses from 4-month-old
      infants to spectral lights. Habituation data were obtained from 92 full-term
      infants separated into one of five groups. Each group viewed either a broadband
      white light (correlated color temperature approximately 2800 K) or one of four
      different spectral lights (lambda d = 470, 510, 570, or 650 nm) approximately
      corresponding to the elemental hues blue, green, yellow and red, respectively,
      for adults with normal trichromatic vision. Stimuli were equated in luminous
      efficiency for a standard infant observer. Stimulus fixation was recorded for
      twelve 10-s presentations, each separated by 10-s interstimulus intervals (ISIs).
      The results show that mean fixation times to the red and green lights were
      significantly greater than those for the blue and white light. Mean fixation time
      for the yellow light was also reduced (significantly) compared to the red but not
      the green light. These results suggest that the chromatic properties of red and
      green spectral lights may be more sensitizing to infants than those of the blue,
      yellow, or white lights.

PMID- 9142504
TI  - The ontogeny of antipredator behavior in paradise fish larvae (Macropodus
      opercularis) IV. The effect of exposure to siblings.
AB  - Twenty-five-day-old larval paradise fish show less avoidance behavior toward a
      model predator than 20-day-old fish larvae. Laboratory experiments tested two
      possible hypotheses: The decrease of avoidance behavior is the result of (a)
      change in the size ratio of larvae/model, or (b) experience with larval siblings.
      Larval paradise fish did not show greater avoidance of larger models or models
      with larger eyespots. However, if isolated for 3 days, the antipredator behavior
      of 25-day-old larvae became similar to younger ones. In further experiments, we
      raised the larvae in a larger holding tank in order to decrease the rate of
      encounters among conspecifics. In line with our assumptions, these larvae also
      showed enhanced avoidance toward a model predator. In sum, our experiments
      revealed that the continuous exposure to conspecific larvae was the main cause
      for the reduced antipredator behavior toward models. To account for our results,
      we suggest that larvae of nonschooling paradise fish habituate to the continuous
      presence of larval conspecifics and, as a result, they show decreased avoidance
      to the model predator. We hypothesize that this habituation process might not
      work in other fish species that show early schooling behavior in their
      development. In other words, they would not generalize the experience of
      conspecifics to potential predators.

PMID- 9142505
TI  - Sensitivity to the motoric effects of a dopamine receptor antagonist differs as a
      function of age at the time of dopamine depletion.
AB  - The ability of the mixed D1/D2 dopamine (DA) receptor antagonist cis-flupentixol
      to impair locomotor behavior in adult rats depleted of DA as weanlings was
      determined. Rats received lateral ventricular injections of 6-hydroxydopamine
      (100-200 micrograms/hemisphere) or its vehicle solution on postnatal Day 20, 27,
      or 35. We compared the ability of cis-flupentixol (.06, .25, and 1.0 mg/kg. i.p.)
      to impair the initiation of voluntary locomotion (i.e., akinesia) in control and
      DA-depleted subjects. Despite the fact that analyses of tissue homogenates
      revealed comparably large (93-96%) depletions of striatal DA across the three
      ages, the lesioned animals differed markedly in their sensitivity to the
      behavioral effects of the receptor antagonist. Surprisingly, rats depleted of DA
      on Day 20 or 27 were no more sensitive than vehicle-treated controls to the
      akinesia-inducing effects of each dose of flupentixol. In contrast, rats depleted
      of DA on Day 35 were supersensitive to the effects of the drug as they exhibited
      akinesia after a low dose of flupentixol that had no effect in any controls or
      animals depleted of DA at younger ages. These results suggest clear age-dependent
      differences in the plasticity of residual striatal DA neurons following subtotal
      damage.

PMID- 9142506
TI  - Mother-infant interactions in two strains of rats: implications for dissociating
      mechanism and function of a maternal pattern.
AB  - Mother-infant interaction was observed in Long-Evans and Fischer 344 rats after
      fostering within or across strains. Interactions immediately following
      introduction of foster pups to the cage as well as undisturbed interactions with
      resident litters were examined. Some differences were related to alien status,
      some to strain of pups, and others to strain of dams. Greater responsiveness to
      pups of the maternal strain was exhibited in retrieval and body licking. Long
      Evans pups received more crouching from dams of both strains 3-12 days
      postpartum, perhaps because they are significantly larger. Regardless of pup
      strain, Long-Evans dams engaged in more maternal licking than did F344 dams, and
      this was more likely directed to the anogenital region. Dams of both strains were
      more likely to lick male than female pups, regardless of pup strain. The strain
      difference in maternal licking is consistent with adult strain differences in
      water and salt appetite and may contribute developmentally to the superior
      copulatory performance of Long-Evans males.

PMID- 9142508
TI  - Ontogenetic differences in retention of spatial learning tested with the Morris
      water maze.
AB  - Two experiments examined retention of spatial learning in rats using a Morris
      water maze. Retention was scored in terms of probe trial performance when the
      platform was removed. Latency to reach the platform location, percent of time in
      the quadrant that had contained the platform, and relative frequency of visits to
      the platform location were analyzed. Results of the first experiment showed that
      preweanlings and juveniles exhibited substantial forgetting at 3- and 7-day
      retention intervals. Forgetting in adults was much lower than that found in the
      younger animals, and no differences in amount of forgetting appeared between the
      3- and 7-day retention intervals at any age. The second experiment showed that
      forgetting in juveniles was alleviated by a single training trial administered
      just prior to the probe trial. These results are discussed in terms of
      ontogenetic differences in memory processing and measurement issues pertinent to
      the Morris water maze test procedure.

PMID- 9142507
TI  - A kinematic comparison of L-DOPA-induced air-stepping and swimming in developing
      rats.
AB  - In Experiment 1, rats of 5, 10, 15, and 20 days of age were injected with L-DOPA
      to elicit stepping and videotaped while suspended in air and in warm water. Inter
      and intralimb coordination were similar for L-DOPA-induced air-stepping and
      swimming at all ages. Other parameters of locomotion, such as step length and
      step rate, varied by substrate. In Experiment 2, pups of 5 to 20 days of age
      received an injection of L-DOPA or the vehicle and were videotaped while freely
      swimming. L-DOPA-induced free swimming was more stereotyped and "automatonlike"
      than that of vehicle-injected animals. Through 15 days of age, all pups swam
      using all four limbs, but L-DOPA induced stricter synchrony of movement in
      diagonal limbs than was used by pups injected with the vehicle. At postnatal Day
      20, vehicle-injected pups adopted the adult swimming pattern in which only the
      hindlimbs were used, whereas L-DOPA-injected pups continued to use the immature
      pattern, diagonal progression with all four limbs. These results suggest that L
      DOPA-induced air-stepping and swimming are manifestations of the same central
      mechanisms and that parameters of L-DOPA-induced stepping are modified by the
      sensory and/or biomechanical effects of the substrate. Although the free swimming
      of L-DOPA-injected pups was kinematically similar to vehicle-treated pups, L-DOPA
      retarded transition to the adult swimming pattern.

PMID- 9142509
TI  - Management of urinary incontinence in the elderly.
AB  - Urinary incontinence is common in the elderly, affecting 6-8% of people over 64
      years in the community and up to 31% in hospital and long-term care. It is
      possible to establish the diagnosis clinically in most incontinent patients with
      the likelihood of improving symptoms in the majority. Treatment of patients with
      urinary incontinence requires attention to general and specific measures. General
      measures include moderation of fluid intake to about 1.5 litres/day, reduced
      intake of caffeine-rich drinks, treatment of aggravating conditions such as
      urinary infection, oestrogen deficiency, increased solute load as in diabetes
      mellitus and uraemia, and drugs like diuretics, sedatives and antidepressants.
      Specific measures include pelvic floor exercises, vaginal cones, interferential
      therapy and oestrogens for patients with stress incontinence. Bladder retraining
      and anticholinergic drugs are for patients with urge incontinence, and alpha
      blockers and 5-alpha reductase inhibitors for patients with overflow incontinence
      due to prostatic hyperplasia.

PMID- 9142510
TI  - Overactivity of tumor necrosis factor-alpha but not interleukin 6 is associated
      with low natural killer cytotoxic activity in the elderly.
AB  - In this paper we asked whether the increased production of two proinflammatory
      cytokines-tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL6) in the
      absence of the inflammatory stimulus, a phenomenon frequently occurring in the
      elderly, may contribute to the decrease of natural killer (NK) cytotoxic
      activity. NK cell activity is a part of a nonspecific immunity directed against
      infected and transformed cells. We measured the levels of bioactive TNF alpha and
      IL6 during cytotoxic NK reactions and analyzed the effect of neutralizing
      monoclonal antibodies anti-TNF alpha and anti-IL6 on the outcome of cytotoxic
      reaction. Bioactive TNF alpha was produced in higher amounts during cytotoxic
      reactions of the elderly with low NK activity in comparison with its production
      by the elderly with high NK activity. Anti-TNF alpha decreased already low
      cytotoxic responses of the elderly while not having an effect on the cytotoxic
      potential of high responders. More of the bioactive IL6 was released during
      cytotoxic reactions of the elderly as compared with young people. There was,
      however, no relation between the height of NK cytotoxic activity and the amount
      of IL6. Our results suggest that the increased level of TNF alpha seen in the
      elderly low NK responders may pose a compensatory mechanism, necessary to keep
      the highest possible level of NK responses. The increased bioactivity of IL6
      during NK reaction of the elderly does not seem to participate in the regulation
      of the level of NK cytotoxic activity.

PMID- 9142511
TI  - Dementia-free life expectancy among elderly Japanese.
AB  - A 3-year prospective cohort study was conducted to estimate the life expectancy
      free of dementia (dementia-free life expectancy) in a representative sample of
      older persons living in an urban Japanese community. For the persons aged 65
      years and older, who were not demented at the baseline survey in 1988, mortality
      and incidence rates of dementia were calculated. At the age of 65 years, males
      showed a total life expectancy of 18 years, including 16 years free of dementia,
      and females showed a total life expectancy of 23 years, including 18 years
      without dementia. At 65 years, the dementia-free life expectancy represented 89%
      of the total life expectancy for males and 79% for females. Total life expectancy
      and dementia-free life expectancy were longer among females than among males.
      However, the life-years with dementia were longer among females. This result
      would be attributable to a higher incidence of dementia and a lower mortality
      among females.

PMID- 9142512
TI  - HLA phenotypes in healthy aged subjects.
AB  - One hundred and seventy-one unrelated elderly healthy subjects selected according
      to the Senieur protocol (57 men and 114 women), aged 75-104 years, and 405
      healthy individuals (238 men and 167 women), aged 18-65 years, were typed for HLA
      A, HLA-B, and HLA-DR antigens. The purpose of the study was to investigate a
      possible association between HLA antigens and longevity. In the total group of
      elderly, an increased frequency of HLA-B16 (11.11 vs. 5.43%) and HLA-DR7 (38.33
      vs. 15.67%) and a decreased frequency of HLA-B15 (1.75 vs. 5.18%) and HLA-DR4
      (11.66 vs. 24.15%) were observed. The HLA-B15DR4 haplotype was not represented
      (vs. 2.1%), HLA-A1B8 was found with a low frequency (2.9 vs. 4.4%), and HLA-B8DR3
      was very rarely found (1.6 vs. 10.1%), whereas the HLA-B13DR7 haplotype was
      observed with an increased frequency (6.6 vs. 3.3%). These results are in
      agreement with other published data and suggest that longevity in humans may be
      influenced by the genetic background.

PMID- 9142513
TI  - Insulin exposure and aging theory.
AB  - The underlying mechanism of calorie restriction (CR) extension of mammalian life
      spans operates by altering the rate of decline in reserve capacity (with time) as
      well as the exposure to growth stimulus, two mechanisms that seem to be related
      to the central genetically determined mechanism that controls mammalian life span
      over a 50-fold range. While genetic control is principally exerted at the level
      of metabolic rate and entrained protective defenses, CR appears to alter the rate
      of decline in reserve capacity and the exposure to growth stimulus without
      appreciable alteration of metabolic rate. CR accomplishes this by lowering the
      nutritionally driven level of insulin exposure, which in turn lowers overall
      growth factor exposure, improves age-declining maintenance of mitochondrial
      maximal function, and maintains a longer-term favorable balance of the
      insulin:growth hormone antagonism. Obtaining the 'halved' insulin exposure in
      calorie-restricted animals (relative to ad libitum fed) can be specifically
      targeted in non-obese ad libitum fed humans by multiple techniques, a situation
      that may confer most of the life span extension of CR without restricting
      calories. The prospect for even further extension of the human life span is
      considered.

PMID- 9142514
TI  - Detailed quality of life assessment in patients treated with primary radiotherapy
      for squamous cell cancer of the base of the tongue.
AB  - BACKGROUND: This study was conducted to evaluate quality of life in patients
      treated with primary radiotherapy (RT) for cancer of the base of tongue. METHODS:
      From 1981 to 1990, 36 patients with primary squamous cell cancer of the base of
      tongue were managed with primary radiotherapy. Ages ranged from 35 to 71 years
      (median, 58 years), T Stage was: T1, n = 11; T2, n = 14; T3, n = 10; T4, n = 1.
      Thirty-one patients (86%) had palpable cervical lymph node metastases at initial
      examination (N1, n = 16; N2, n = 11; N3, n = 4). Patients received external beam
      RT to their primary site and necks, followed by a brachytherapy boost to the
      tongue. Those with neck nodes also had a neck dissection. The median follow-up is
      5 years (minimum, 3 years). Actuarial 5-year local control was 85%; regional
      control was 96%; distant metastases-free survival was 87.5%; and overall
      survival, 85%. Twenty-nine of the 30 long-term survivors completed (1) Memorial
      Symptom Assessment Scale (MSAS), (2) Functional Assessment of Cancer Therapy
      (FACT), (3) Performance Status Scale for Head and Neck Cancer (PSS), and (4) a
      sociodemographic and economic questionnaire. At the time of cancer diagnosis, 62%
      were employed full-time, and 21% were employed part-time; 83% were earning >
      $20,000/year, and 59% were earning > $60,000/year. RESULTS: At follow-up, annual
      incomes were similar to those at initial examination. Of those who had been
      working full-time, 72% were still in full-time work, and of those who had been
      working part-time, 83% were still in part-time work. Average PSS scores were 90
      for eating in public, 96 for understandability of speech, and 68 for normalcy of
      diet. On the MSAS, the following symptoms had prevalence: > 30% xerostomia,
      difficulty swallowing, decreased energy, pain, worrying, insomnia, cough, drowsy,
      change in taste, and irritability. Scores on the FACT exceeded published values
      collected for a mixed cancer population. CONCLUSIONS: The overwhelming majority
      of patients achieved excellent functional status and quality of life and could
      maintain their prediagnosis earning potential and employment status after primary
      radiation for advanced base of tongue cancer.

PMID- 9142515
TI  - Retropharyngeal lymphadenopathy in nasopharyngeal carcinoma.
AB  - BACKGROUND: This study was done to investigate the size of normal retropharyngeal
      lymph nodes (RLN) and the incidence of retropharyngeal lymph node involvement in
      patients with nasopharyngeal carcinoma (NPC). METHODS: Forty-four NPC patients
      who had not yet received treatment and 20 control subjects underwent MRI
      scanning. The number and the maximum diameter of the short axis of the cervical
      lymph nodes were measured. The number of nasopharyngeal walls involved and the
      maximum diameter of the tumor were recorded. RESULTS: In 5 of 20 control subjects
      lateral RLN were identified; none of these nodes was greater than 2.5 mm. In the
      NPC patients, taking 4 mm as the upper limit of normal RLN, 89% of the patients
      had enlarged RLN. The number of nasopharyngeal walls involved and the maximum
      diameter of the primary tumor showed no statistical relationship with the
      involvement of RLN. There was a statistical association between RLN and level II
      node involvement, but not with other groups of neck nodes. CONCLUSION: Of all
      patients with NPC, 89% showed enlarged RLN. Its involvement was related to level
      II nodes but not to the number of nasopharyngeal sites involved nor with the
      maximum diameter of the tumor.

PMID- 9142516
TI  - Cutaneous nasal malignancies: is primary reconstruction safe?
AB  - BACKGROUND: The nose is particularly vulnerable to cutaneous malignancies, making
      it the most common location for presentation. Recurrence of these cutaneous
      lesions is not uncommon, often compromising the timing of nasal restoration. It
      is the purpose of this report to reexamine the safety of primary nasal
      reconstruction in selected patients. METHODS: Seventy-one patients who underwent
      nasal reconstruction at The University of Texas M. D. Anderson Cancer Center
      between 1987 and 1995 were retrospectively reviewed. There were 35 men and 36
      women with an average age of 60 years. All nasal reconstructions were performed
      for defects secondary to malignancies. Basal cell carcinoma was the most common
      lesion (n = 49), followed by squamous cell carcinoma (n = 10) and melanoma (n =
      7), with five additional variable malignancies. The most common location of the
      cutaneous lesions was the nasal dorsum, and the forehead flap was the most common
      adjacent tissue used for reconstruction. Immediate reconstruction was performed
      for 42 of the basal cell carcinomas, 6 of the squamous cell carcinomas, 6
      melanomas, and 3 other lesions. Delayed restoration was performed for 7 basal
      cell carcinomas, 4 squamous cell carcinomas, 1 melanoma, and 2 additional
      lesions. The average time between surgical extirpation and the start of nasal
      reconstruction was 8.2 months for basal cell carcinoma, 29 months for squamous
      cell carcinoma, and 10 months for melanoma. RESULTS: Twenty-six recurrent lesions
      were identified at an average of 36 months after extirpation. Despite these
      numbers, only three recurred after nasal reconstruction at our institution.
      Follow-up averaged 41 months, with none less than 1 year. Seventy patients are
      still alive with no evidence of disease. CONCLUSION: Primary reconstruction is
      safe in selected patients. Surgical delay in reconstruction should be considered
      if margins are questionable, the pathology is determined to be aggressive, if
      there is perineural or deep bony invasion, or if postoperative radiotherapy is to
      be initiated. Nasal reconstruction ultimately is based upon a complex series of
      issues but can be performed with few complications in an effort to restore self
      image.

PMID- 9142517
TI  - Comparison of three prophylactic antibiotic regimens in clean-contaminated head
      and neck surgery.
AB  - BACKGROUND: Although appropriate perioperative antibiotic prophylaxis has
      significantly reduced wound infection rates in clean-contaminated head and neck
      surgical procedures, controversy still remains regarding the optimal antibiotic
      regimen. METHODS: In this prospective, double-blind clinical trial, 159 patients
      were randomized to receive amoxicillin-clavulanate, clindamycin plus gentamicin,
      or cefazolin intravenously up to 1/2 hour before surgery and at 6-hour intervals
      for an additional three doses. RESULTS: An overall wound infection rate of 23%
      was observed. Thirteen (22.8%) infections occurred in the amoxicillin-clavulanate
      treated group, 11 (21.2%) in the clindamycin plus gentamicin-treated group, and
      13 (26%) in the cefazolin-treated group, which was not statistically significant.
      Only prior medical illnesses, such as chronic obstructive pulmonary disease and
      diabetes mellitus, correlated with an increased wound infection rate (p = 0.018).
      CONCLUSIONS: Amoxicillin-clavulanate, clindamycin plus gentamicin, and cefazolin
      seem to have similar efficacy when administered prophylactically in clean
      contaminated head and neck surgical procedures.

PMID- 9142518
TI  - Postoperative radiation of open head and neck wounds--updated.
AB  - BACKGROUND: Postoperative radiotherapy is commonly used in treating head and neck
      cancer. A concern is the possibility of an unhealed surgical wound delaying or
      disrupting the treatment schedule. Our institution previously reported our
      experience on the outcome of radiotherapy on unhealed wounds from 1977 to 1984.
      METHODS: In an effort to update and enlarge this series, we reviewed the charts
      of patients receiving postoperative radiotherapy from 1985 to 1990. Of 267
      patients, 20 had unhealed wounds or fistulas at the beginning of treatment. The
      wounds healed spontaneously in 17 of these patients, 1 required surgical closure,
      and 2 never healed. Combining our current and previous series, 452 patients had
      onset of postoperative radiation therapy at our institution from 1977 through
      1990, of whom 33 had unhealed wounds at the onset of irradiation. RESULTS: In 22
      of 33 (67%) patients, the wounds healed spontaneously (mean: 98 days, range: 36
      to 304 days). Five additional patients achieved successful wound healing
      following surgical closure (mean: 281 days, range; 112 to 608 days). The
      remaining 6 patients died before healing was complete (4 patients) or were lost
      to follow-up (2 patients) at 16 and 27 months before wound healing occurred. Nine
      patients in this study are alive with no evidence of disease, 19 died of cancer,
      and 5 died of other causes. CONCLUSIONS: When there are indications to deliver
      irradiation in the postoperative setting, it is desirable to initiate treatment
      within 6 weeks of the data of surgery. Although it is preferable to have
      completely closed operative wounds prior to irradiation, some consideration must
      be given to initiating irradiation in the face of incompletely closed wounds when
      it is anticipated that healing time will be prolonged. In some patients, the
      wounds continue to heal during the course of irradiation, or will stabilize, and
      can be surgically managed after irradiation is completed or may spontaneously
      heal after treatment. Excessive delays in initiating appropriate cancer therapy
      may lead to recurrence prior to irradiation; such recurrences are rarely
      successfully salvaged.

PMID- 9142519
TI  - Laryngeal carcinoma in patients without a history of tobacco and alcohol use.
AB  - BACKGROUND: The medical literature on laryngeal carcinomas in patients without a
      history of tobacco and alcohol use is sparse. METHODS: A retrospective review of
      933 laryngeal carcinomas treated in our center between January 1984 and December
      1993 was made. Characteristics and results of patients with history of tobacco
      and alcohol use were compared with those who used neither. RESULTS: Of all
      patients with laryngeal carcinomas, 31 (3.3%) had no history of tobacco and
      alcohol use. In this group of patients, distribution between sexes was similar,
      and the mean age of patients was 70 years, compared with 63 years in the group
      with a history of tobacco and alcohol use. The survival rate was better in the
      former group. CONCLUSIONS: Patients without a history of tobacco and alcohol use
      who developed laryngeal cancer showed different characteristics compared with
      smokers or drinkers; they were an average of 10 years older, they showed no male
      predominance, and their lesions were mainly located in the glottis, which
      permitted early diagnosis and a higher survival rate.

PMID- 9142520
TI  - Depth of invasion as a predictive factor for cervical lymph node metastasis in
      tongue carcinoma.
AB  - BACKGROUND: Many histopathologic parameters in head and neck squamous cell
      carcinoma have been identified as predictive factors for cervical metastasis.
      Several studies focused on tumor thickness, and the depth of invasion was
      suggested to have a relationship to the occurrence of cervical metastasis.
      Nonetheless, the criterium for elective neck therapy in terms of tumor depth is
      still inconclusive. Therefore, a retrospective study was undertaken to
      substantiate the differing results in the literature with our own findings
      concerning the interrelationship between tumor thickness and clinically
      suspicious neck, as well as occult neck disease. In addition, the study attempted
      to identify further predictive factors for cervical metastasis in squamous cell
      carcinoma of the tongue. METHODS: The medical records of 34 primary tongue
      carcinomas operated without any preoperative therapy between 1980 and 1991 were
      reviewed. Each patient's tumor type, tumor location, tumor size, invasion mode,
      depth of invasion, intralymphatic tumor emboli, and perineural invasion were
      evaluated. Chi-square contingency tables were used to correlate clinical or
      histopathologic parameters with metastasis in the neck. RESULTS: The overall
      cervical metastatic rate was 35.3% (n = 12/34). In univariate analysis, invasion
      mode and depth of invasion were statistically significant predictors of regional
      metastasis at p = 0.0019 and p = 0.0003, respectively. In the group in which
      tumor depth exceeded 5 mm, the metastatic rate was 64.7% (11/17). In contrast,
      when the depth of invasion was less than 5 mm, the incidence of cervical
      metastasis was 5.9% (1/17). Clinically negative necks turned out pathologically
      positive in 30.0% (n = 9/30). The tumor depth exceeded 5 mm in 43.4% (13/30) of
      the N0 necks. In the conversion (N0-->N1) group, tumor depth exceeding 5 mm was
      noted in 88.9% (n = 8/9). CONCLUSIONS: We suggest that there is a discerning
      point at 5 mm of tumor depth at which cervical metastasis is probable. Electric
      neck therapy (surgery or irradiation) is strongly indicated for tumors exceeding
      5 mm invasion. Tumor invasion mode and tumor size also bear an impact on the
      indication for therapy.

PMID- 9142521
TI  - Tracheal advancement flap for postlaryngectomy stomal stenosis.
AB  - BACKGROUND: Tracheal stenosis can be a troubling consequence of laryngectomy.
      Some revision techniques disturb the posterior stoma site of a current or planned
      tracheoesophageal puncture (TEP). METHODS: A revision technique which advances
      the trachea out of the stoma, divides the anterior tracheal wall, and leaves the
      posterior tracheal wall undisturbed was designed. The paper describes the
      technique in detail. "Success" was defined as producing a stable, trouble-free
      stoma requiring no stenting; "partial success" as an improved stoma requiring
      some stenting; and "failure" as no improvement and continuous stenting. RESULTS:
      Fifteen patients underwent the procedure. Median time from laryngectomy to
      revision was 10 months. Preoperative to postoperative median stoma size increased
      from 63 mm2 to 135 mm2. Seven patients were classified as successful, six
      patients were partially successful, and two patients had no improvement.
      CONCLUSION: The tracheal advancement flap is a safe technique for the
      laryngectomy patient who has undergone or might undergo voice restoration.

PMID- 9142522
TI  - Lack of serologic evidence for Helicobacter pylori infection in head and neck
      cancer.
AB  - BACKGROUND: Several epidemiologic investigations have established a link between
      Helicobacter pylori infection and gastric malignancies. Because the stomach is in
      continuity with the oral cavity and the bacterium has been isolated from dental
      plaque and saliva, we hypothesized that H. pylori infection of the upper
      aerodigestive tract might result in mucosal disruption, allowing for subsequent
      transformation by known carcinogens such as tobacco and alcohol. METHODS: To test
      this hypothesis, we assayed for the presence of IgG antibodies to H. pylori in
      the serum of 21 patients with squamous cell carcinoma of the head and neck
      (SCCHN) and 21 matched controls without a history of head and neck cancer.
      RESULTS: The incidence of seropositivity in the SCCHN patients was 57% and in the
      controls, 62% (p > 0.05). CONCLUSIONS: These data do not support an etiologic
      role for H. pylori infection in head and neck cancer.

PMID- 9142523
TI  - The impact of temporary iodine-125 interstitial implant boost in the primary
      management of squamous cell carcinoma of the oropharynx.
AB  - BACKGROUND: To define the impact of interstitial boost of the oropharynx on local
      control and complications using iodine-125 (I-125) brachytherapy. METHODS:
      Between October 1986 and September 1991, 19 patients with cancer of the
      oropharynx received treatment at William Beaumont Hospital. Primary tumors
      consisted of 13 base of tongue, 4 tonsillar, and 2 pharyngeal wall lesions. All
      patients received 45-66 Gy (median, 54 Gy) external beam irradiation to the
      primary and regional nodes, followed by an interstitial implant of 22-32 Gy
      (median, 25 Gy) with I-125. RESULTS: Median follow-up was 58 months (range, 12-89
      months). Three patients failed within the tumor bed, for a 5-year actuarial rate
      of local control of 83% (T1/T2, 82%; T3/T4, 86%). Two of the three local failures
      were salvaged surgically, for an overall 5-year actuarial local control rate of
      94%. The 5-year actuarial overall survival rate was 64%. Complications included
      one case of soft tissue ulceration and two cases of osteoradionecrosis, all
      managed conservatively. CONCLUSIONS: Patients with cancer of the oropharynx
      judged to be candidates for boosts with interstitial implants can be effectively
      treated with I-125. Local control was excellent, and complications were minimal.

PMID- 9142524
TI  - Glandular odontogenic cyst: a case report and clinicopathologic analysis of the
      relationship to central mucoepidermoid carcinoma.
AB  - Glandular odontogenic cyst (GOC), an unusual multilocular cystic lesion of jaws
      exhibiting the features of both botryoid odontogenic cyst and mucoepidermoid
      tumor has been reported recently as a new entity with uncertain histogenesis. The
      World Health Organization named GOC as an independent pathologic entity and
      classified it as a developmental odontogenic epithelial cyst. We report an
      additional case, describe its clinicopathologic features, and discuss the
      similarity to the central mucoepidermoid carcinoma.

PMID- 9142525
TI  - Supracricoid hemilaryngopharyngectomy conversion to Pearson's near-total
      laryngectomy: a case report.
AB  - BACKGROUND: Pearson's near-total laryngectomy was initially advocated in patients
      with extended glottic carcinoma and hypopharyngeal carcinoma. More recently, the
      utility of near-total laryngectomy for supraglottic pharyngeal, base of tongue,
      and other cancers such as thyroid cancer with anterior tracheal wall invasion has
      also been reported. METHODS: The purpose of this case report was to demonstrate
      the feasibility of this procedure in the setting of severe aspiration after
      supracricoid hemilaryngopharyngectomy. RESULTS: The first case of successful
      conversion from supracricoid hemilaryngopharyngectomy to Pearson's near-total
      laryngectomy in a patient with severe and recurrent aspiration is presented.
      CONCLUSIONS: This case report suggests that when partial laryngopharyngectomy
      results in severe and recurrent aspiration, rather than having to convert the
      patient to a total laryngectomy with tracheoesophageal puncture, a near-total
      laryngectomy is a reasonable option with acceptable functional results.

PMID- 9142526
TI  - Impaired vocal cord mobility in the setting of acute suppurative thyroiditis.
AB  - BACKGROUND: Acute suppurative thyroiditis is an increasingly rare entity,
      accounting for less than 0.1% of thyroid surgery. This is the first report in the
      literature of acute thyroiditis causing a unilateral reversible vocal cord
      paralysis. METHODS: A 41-year-old woman was initially seen with a unilateral
      vocal cord paralysis resulting from acute suppurative thyroiditis. RESULTS: The
      vocal cord paralysis resolved following surgical drainage of the thyroid abscess
      and treatment with intravenous antibiotics. CONCLUSIONS: We present this case to
      emphasize the need for a complete and thorough head and neck exam including
      preoperative documentation of vocal cord mobility.

PMID- 9142527
TI  - Bridging the gap between public expectations and public willingness to pay.

PMID- 9142528
TI  - National health accounts in developing countries: appropriate methods and recent
      applications.
AB  - Better information on the financing of the health sector is an essential basis
      for wise policy change in the area of health sector reform. Analysis of health
      care financing should begin with sound estimates of national health expenditure-
      total spending, the contributions to spending from different sources and the
      claims on spending by different uses of the funds. The member countries of the
      OECD have successfully established such comparative health expenditure accounts
      in terms of standardized definitions of the uses of funds and breakdowns by
      public and private sector sources. This has resulted in important research on
      health system differences which could explain variations in the level and
      composition of financing. The United States has developed a more detailed
      approach called National Health Accounts, which expands the OECD method into a
      more disaggregated 'sources and uses' matrix. In the developing countries,
      analysis of health expenditures has been much less systematic, despite several
      decades of calls by international researchers for more attention. This paper
      reviews previous work done in developing countries and proposes renewed attention
      to national health expenditures, adapting the recent experience of the United
      States. Because most developing countries have more pluralistic health financing
      structures than are found in most industrialized countries, an enhanced and
      adapted version of the 'sources and uses' matrix method is proposed. This method
      should be modified to address the relevant categories of expenditures prevalent
      in the developing countries. Examples of recent applications of such 'national
      health accounts' from the Philippines, Egypt, India, Mexico, Colombia and Zambia
      are presented. Experience to date suggests that development of sound estimates
      using this method in low and middle income countries is feasible and affordable.
      National health accounts estimates can significantly influence policy. They
      provide decision makers with a holistic picture of the health sector, showing the
      actual emphasis of spending and the roles of different payers. They also provide
      a consistent framework for modelling reforms and for monitoring the effects of
      changes in financing and provision. An easy to use software tool has been
      developed for training and data management. Regional networks of collaborating
      national groups are proposed as a first step in expanding use of the method and
      to gain both national and cross-national comparative benefits.

PMID- 9142529
TI  - Health insurance and the homeless.
AB  - There is very little known about health care utilization among the homeless or
      about the role of health insurance on utilization patterns. Many health care
      reform proposals advocate expanding health insurance coverage for various
      segments of society, including the homeless. Although homeless people who lack
      health insurance face strong financial barriers to health services, providing
      them with health insurance may not appreciably increase their demand for health
      care if they also face important non-financial barriers. We investigate the
      relationship between insurance and utilization for this group based on estimates
      from an empirical model of medical care use and insurance coverage. Using our
      estimates, we simulate potential effects of policy changes on various types of
      utilization, including use of mental health services and treatment for alcohol or
      other drug abuse.

PMID- 9142530
TI  - Market concentration in secondary health services under a purchaser-provider
      split: the New Zealand experience.
AB  - The separation of purchaser and provider in government-funded health systems
      enables competition to develop between providers. Competition is seen as a means
      to drive technical efficiencies by providers. While it is difficult to assess
      comprehensively the level of competition in a market taking into account
      contestability and substitutability effects, it is possible to measure the degree
      of market concentration. This paper employs the Hirschman-Herfindahl index to
      provide measures of market concentration in selected secondary health care
      markets in New Zealand immediately prior to (1992) and following (1994)
      implementation of a purchaser-provider split. The results show that, generally,
      the selected markets are highly concentrated and that there has been little
      change in the degree of concentration over the 2 year period under investigation.
      The paper also discusses some of the methodological problems associated with the
      measurement of market concentration and acknowledges the limitations of such
      measures as indicators of competition.

PMID- 9142531
TI  - The impact of health care policy initiatives on productivity.
AB  - This paper analyses productivity growth in health care delivery in Sweden and the
      impact of health care policy initiatives on productivity. In particular we
      consider the maximum waiting time guarantee introduced in Sweden 1992. The
      intention of the maximum waiting time guarantee was to shorten the waiting lists,
      partly through increased productivity. We measure productivity growth by
      estimating Malmquist productivity indices using non-parametric linear programming
      models. The productivity models are applied to data from a sample of public
      ophthalmology departments from 1988 to 1993. Positive productivity changes are
      found in several years, although no significant differences between the periods
      are found.

PMID- 9142532
TI  - Is the person trade-off a valid method for allocating health care resources?
AB  - The Person Trade-Off (PTO) is a methodology aimed at measuring the social value
      of health states. It is claimed that other methods measure individual utility and
      are less appropriate for taking resource allocation decisions. However, few
      studies have been conducted to test the apparent superiority of the method for
      this particular kind of decision. We present a pilot study to this end. The study
      is based on the results of interviewing 30 undergraduate students in economics.
      We compare two well known techniques, the Standard Gamble and the Visual Analogue
      Scale, with the PTO. The criterion against which the performance of the methods
      is assessed is the directly obtained preference about how to establish priorities
      among hypothetical patients waiting for treatment. Apparently the PTO performed
      better than the others. We also compare three different frames for the PTO. One
      of them seems to predict people's preferences.

PMID- 9142533
TI  - The adjustment of cost measurement to account for learning.
AB  - This note discusses the adjustment of cost measurement to account for learning.
      By learning is meant improvements in productive efficiency resulting from use of
      a (health) technology in routine practice. A recently proposed method is shown to
      be potentially misleading. Alternatively, it is suggested that the total cost is
      decomposed in treatment cost and learning cost. Furthermore, if there is
      uncertainty about the long-run unit cost, learning will reveal the true cost. A
      method to adjust the learning cost for the value of this information is
      illustrated.

PMID- 9142534
TI  - Clinical trials and economic evaluations? No, there are only evaluations.

PMID- 9142536
TI  - Health economics e-mail discussion lists.

PMID- 9142535
TI  - The nature of individual preferences: a prologue to Johannesson, Jonsson and
      Karlsson.

PMID- 9142537
TI  - Re-ablement of hand in leprosy.

PMID- 9142538
TI  - The metacarpophalangeal stabilization test: its surgical interest.
AB  - If the fingers of the claw hand are stabilized in order to prevent over-extension
      of the metacarpophalangeal joints, the long extensors will fully extend both
      interphalangeal joints. Based on the proximal interphalangeal stiffness assessed
      by this test, a simple therapeutic plan is proposed for the choice of the
      appropriate techniques for palliative claw hand surgery.

PMID- 9142539
TI  - Two objective "archivable" tests for voluntary muscle testing in ulnar and median
      nerve paralysis.
AB  - Two tests are proposed for assessment of ulnar and median nerve function for use
      under field conditions: (i) "flap flexion" of fingers for ulnar nerve, and, (ii)
      tip-to-tip thumb opposition to the fourth finger for median nerve. These tests,
      which are a part of a series of simple clinical tests proposed for rapid
      neurological evaluation of the function of the nerves involved in leprosy, are
      simple, objective and easy to do. Because these tests depend on the strength of
      muscles tested, they might spare its direct assessment. In fact, it is difficult
      to assess and grade the strength of the little muscles of the hand and that is
      very much dependent on the examiner's own experience. Therefore, it is rather
      subjective. The tests described here may also be used for evaluating the results
      of corrective surgery of the hand. Whenever possible, making photographic records
      of these two tests, to be archived in the forms where everyone can see and
      compare them, seems to be easier and more objective than the subjective
      transcription of the feelings of an examiner assessing the strength of the small
      muscles of the hand. These two tests seem to be most objective for a scientific
      prospective study with a long term follow up. So, they could be used in assessing
      the results of leprosy neuritis by medical treatment, or, by medical treatment
      completed (when necessary only and not routinely) by surgical decompression of
      nerves and also of corrective surgery of claw hand, or, loss of opposition of the
      thumb.

PMID- 9142540
TI  - Surgical correction of claw fingers in leprosy using flexor superficialis direct
      lasso procedure.
AB  - One tendon of Flexor digitorum superficialis split into two or four tails and
      each tail looped around the A1 pulley of one affected finger, was used for
      correcting intrinsic minus deformity of fingers in 144 patients. This operation
      has the advantage of retaining superficialis tendons of the other fingers for
      better power grip and avoiding swan-neck deformity. Satisfactory results were
      noticed in 81 of the 99 patients (82%) followed up. The remaining 18 patients
      showed a variety of problems such as swan neck/check rein deformity in the donor
      finger, skin contracture and recurrence of clawing.

PMID- 9142541
TI  - Prevention of post-operative "sublimis minus" deformity by modified surgical
      procedure at the donor finger.
AB  - "Sublimis minus" deformity occurs quite often as a post-operative deformity in
      the donor finger after transfer of the flexor superficialis tendon e.g., for
      paralytic claw finger correction. Our experience with a new procedure to avoid
      this outcome is described here. Long term results in 35 cases are very
      encouraging and the new procedure promises to be useful to prevent sublimis minus
      deformity. It also opens out a wider range of discretion given to hand surgeons
      to use the sublimis tendon more freely for transfers.

PMID- 9142542
TI  - Unfavourable results after surgical correction of claw fingers in leprosy.

PMID- 9142543
TI  - A double synergistic approach to correction of the intrinsic minus hand.
AB  - In the search of a method for the correction of the intrinsic minus hand with
      simplified post-operative physiotherapy training, preferably dynamic methods
      acting in a synergistic way, two methods were identified, one correcting clawing
      in extension, the other correcting clawing in flexion under strain. Forty-three
      patients (53 hands) were operated upon using a combination of the methods. The
      immediate post-operative results showed that 50 of the hands had satisfactory
      result. Twenty patients (26 hands) were traced and reviewed after 0.5-5.5 years
      (average 2.75 years) and 14 of these hands showed good, 11 fair, and one poor
      result. All patients reported that their hand function had improved after
      correction. Post-operatively, the physiotherapy staff were only required to
      exercise active extension and flexion of the fingers. The advantages and
      disadvantages of the approach are discussed. The method requires an experienced
      surgeon but the post-operative training is simple and there is no need for re
      education of transferred tendons. I have found the method useful for patients
      with difficulties in re-education and for patients in programmes where the
      physiotherapy back up is less developed.

PMID- 9142545
TI  - Comparative study of some procedures for correction of claw fingers in leprosy.

PMID- 9142544
TI  - Application of "measured tension" technique in correction of claw fingers by
      tendon transfer in leprosy.

PMID- 9142546
TI  - The need for controlled studies in tendon transfer surgery of the hand.

PMID- 9142547
TI  - Restoration of abduction-opposition in paralysed thumb in leprosy.

PMID- 9142548
TI  - The distally based posterior interosseous fasciocutaneous island flap in
      reconstruction of the hand in leprosy.
AB  - In leprosy a functionally useless hand can be the sequelae of resorption of the
      sensation-impaired thumb and fingers resulting from repeated trauma and
      infection. When this process shortens the thumb to the level of the proximal
      phalanx or metacarpal, the effect is to produce a relatively shallow first web
      space which together with the shortening, can prevent the most basic hand
      manoeuvre of a pincer or pinch grip. The reconstructive procedure commonly used
      in this situation is to widen and deepen the web space with a z-plasty combined
      with excision of the second metacarpal but the result can be inadequate. We have
      used the posterior interosseous fasciocutaneous island flap, both as a simple and
      a compound flap, to solve this challenging problem and we report here our
      experience with four patients.

PMID- 9142549
TI  - Flexor aponeurotic release for resistant adaptive shortening of long flexors in
      claw hands in leprosy.
AB  - Adaptive shortening of long flexors (ASLF) is a consequence of long-standing
      neglected claw finger deformity. While adaptive shortening of muscle fibres is
      correctable by physiotherapy, concurrent shortening of
      fascia/aponeurosis/intermuscular septum, composed of inelastic collagen fibres is
      not. Surgical excision of these structures has been advised in ASLF in cerebral
      palsy. This procedure in which a 3-4 cm wide band of deep fascia of the forearm,
      about 6 cm distal to the medial epicondyle, along with the intermuscular septum
      is excised was tried in seven patients having severe or moderately severe ASLF
      with good results. This procedure is worth a more extensive trial.

PMID- 9142550
TI  - Sensory re-ablement of the hand in leprosy: the next surgical frontier.

PMID- 9142551
TI  - Nutrition and cardiovascular disease.

PMID- 9142552
TI  - Hormonal requirement for blastocyst implantation and a new approach for anti
      implantation strategy.
AB  - There is a growing awareness of a need for developing novel methods of
      contraceptive technology which should not only be effective in providing
      protection against conception but also take into consideration the reproductive
      health issues confronting men and women. This paper considers the process of
      embryo implantation as one such potential target. The hormonal basis of embryo
      implantation in primates has been discussed to indicate that progesterone, and
      not estrogen, from ovarian source is the primary determinant of embryo
      endometrial maturation and their synchronization for implantation. Thus, low dose
      administration of the anti-progesterone, mifepristone, during early luteal phase
      has been shown to be an effective anti-implantation approach to for fertility
      control. Furthermore, the dissociation of endometrial-hormonal synchrony at the
      time of blastocyst implantation following the post-ovulatory mifepristone
      administration has been shown to be the physiological basis of its anti
      implantation effect with undisturbed circulatory hormone profiles and ovarian
      functions. Further studies are required to appreciate the full potential and to
      mollify the limitations of this approach.

PMID- 9142553
TI  - Insights into the mechanism of action of benzoyl peroxide as a tumor promoter.
AB  - A comparison of the mechanism of action of benzoyl peroxide, a tumor promoter was
      studied in three different cell lines i.e. NIH 3T3, HDCS and A431. Benzoyl
      peroxide was found to mediate its effect by inducing poly ADP-ribosylation in all
      the three cell types studied but to different extents, with histone H1 serving as
      a common acceptor for poly ADP-ribose. It also stimulated the activities of the
      antioxidant enzymes CuZn superoxide dismutase and catalase in NIH 3T3 and HDCS
      cells, but not in A431. Alterations in the expression of c-jun and c-fos were
      observed in NIH 3T3 and A431 cells. Benzoyl Peroxide appeared to mediate its
      effect via genetic and epigenetic mechanisms.

PMID- 9142554
TI  - Role of midbrain ventro-lateral tegmental area (VTA) enkephalinergic mechanisms
      in the facilitation of hypothalamically-induced predatory attack behaviour.
AB  - Bipolar concentric electrodes were implanted in five cats in extreme lateral
      regions of hypothalamus. These sites were electrically stimulated using biphasic
      square wave pulses at a current strength ranging from 300-800 microA to evoke
      predatory attack on an anaesthetized but live rat. At lower current strength (300
      microA) only alertness with pupillary dilatation was produced. Gradual increase
      in the current strength led to the recruitment of somatic and affective
      components and a predatory attack was exhibited at a mean current strength of 700
      microA. A scoring system allowed the construction of stimulus response curves,
      which remained fairly constant when repeated over a period of 3-4 weeks.
      Bilateral microinjections of delta-alanine methoinine enkephaline (DAME) (500 ng
      in 0.5 microliter saline) in ventrolateral tegmental area (VTA) elevated the mean
      threshold current strength for affective components while somatomotor components
      were totally inhibited. The blocking effect of DAME persisted for 1 hour.
      Microinjections of naloxone (1 microgram) in similar volumes facilitated the
      response as indicated by a reduction in threshold current strength for
      somatomotor and affective components. Microinjections of naloxone (1 microgram)
      in similar volumes facilitated the response as indicated by a reduction in
      threshold current strength for somatomotor and affective components.
      Microinjections of naloxone (1 microgram) also reversed the blocking effect of
      DAME and the thresholds returned to the control level within 10 min while
      microinjection of normal saline as control had no effect. The excitatory effects
      of naloxone and inhibitory effects of DAME were statistically significant at P <
      0.01 and P < 0.05 respectively with Wilcoxon's signed rank test. The present
      study indicates that enkephalinergic as well as opioidergic mechanisms operating
      at the midbrain (VTA) level are involved in the inhibition of predatory attack as
      elicited from lateral hypothalamus.

PMID- 9142555
TI  - Effect of aspartate and glutamate on nociception, catalepsy and core temperature
      in rats.
AB  - Effects of excitatory aminoacids (EAAs) aspartate (ASP) and glutamate (GLU) in a
      low (50 ng, i.c.) and high dose (20 micrograms, i.c.), were studied on
      nociception, catalepsy and rectal temperature in albino rats. Both ASP and GLU
      altered the tail flick reaction time to thermal stimulation in a dose dependent
      manner, increasing it with low doses and reduced with high doses. Naloxone (10
      micrograms, ic) antagonized the anti-nociceptive effect of EAAs while ketamine
      (10 micrograms, ic)-a NMDA receptor antagonist antagonized the hyperalgesic
      effect. These EAAs also antagonized catalepsy induced by haloperidol,
      chlorpromazine, trifluoperazine and morphine. Both ASP and GLU produced a
      hyperthermic response in all animals, including those in which hypothermia was
      induced by reserpine. These EAAs produced a comparable central modulatory effects
      on nociception, catalepsy and core temperature.

PMID- 9142556
TI  - Pranayama increases grip strength without lateralized effects.
AB  - The present study was conducted to determine whether breathing through a
      particular nostril has a lateralized effect on hand grip strength. 130 right hand
      dominant, school children between 11 and 18 yrs of age were randomly assigned to
      5 groups. Each group had a specific yoga practice in addition to the regular
      program for a 10 day yoga camp. The practices were: (1) right-, (2) left-, (3)
      alternate- nostril breathing (4), breath awareness and (5) practice of mudras.
      Hand grip strength of both hands was assessed initially and at the end of 10 days
      for all 5 groups. The right-, left- and alternate-nostril breathing groups had a
      significant increase in grip strength of both hands, ranging from 4.1% to 6.5%,
      at the end of the camp though without any lateralization effect. The breath
      awareness and mudra groups showed no change. Hence the present results suggest
      that yoga breathing through a particular nostril, or through alternate nostrils
      increases hand grip strength of both hands without lateralization.

PMID- 9142557
TI  - Investigations of anti-inflammatory activity of Jigrine.
AB  - Jigrine, a polypharmaceutical herbal formulation containing 14 medicinal plants
      is used in the Unani system of medicine for the treatment of liver ailments. The
      antiinflammatory activity of Jigrine (0.5 ml and 1.0 ml/kg, po), was evaluated
      against acute inflammation caused by carrageenin (injecting 0.1 ml of 1%
      carrageenin in 0.9% NaCl solution into plantar surface of the hind paw of the
      rat) and the effect of Jigrine (1 ml/kg/day, po for 7 days) was also studied on
      the sub-acute inflammation induced by cotton pellet granuloma. The paw volume,
      biochemical parameters like tissue AST, ALT, gamma-GTP and lipid peroxides and
      dry wt. of granuloma were measured to assess the anti-inflammatory activity. It
      showed a significant anti-inflammatory activity as evidenced by lowering the
      elevated levels of paw volume and biochemical parameters. But it could not reduce
      the sub-acute inflammation caused by cotton pellet granuloma. The study suggests
      that Jigrine has significant effect only on acute phase of inflammation caused by
      carrageenin. Antioxidant and membrane stabilizing action of Jigrine might be
      responsible for its anti-inflammatory effect.

PMID- 9142558
TI  - Effect of Ocimum sanctum Linn on noise induced changes in plasma corticosterone
      level.
AB  - Ethanol extract of leaves of ocimum sanctum was screened for its antistressor
      actions against acute and chronic noise stress in albino rats by investigating
      the plasma corticosterone level in these animals. There was a significant
      elevation of the corticosterone level in plasma of rats subjected to 30 min noise
      (100 dB) stress. Chromic exposure (4 hr daily for 30 days) to noise with same
      intensity reduced the hormonal level significantly. Treatment of animals with
      ethanol extract of Ocimum sanctum prevented the changes in plasma level of
      corticosterone induced by exposure to both acute and chronic noise stress,
      indicating the antistressor property of the plant against noise.

PMID- 9142559
TI  - Antinociceptive activity of chromophoric chain substituted hemicyaninocolourants.
AB  - Some of the chromophoric chain substituted hemicyaninocolourants (CCHCs) were
      synthesized and confirmed on the basis of nitrogen analysis. These were tested
      for their antinociceptive activity in albino rats against tail flick technique
      and sodium chloride induced writhing test. Test compounds were given in graded
      doses (10, 20 and 50 mg/kg, intraperitoneally) and compared with morphine and
      aspirin as standard controls. Two compounds CCHC-1 and CCHC-2 showed
      antinociceptive activity in a dose-dependent manner in both the experimental
      models. The compound CCHC-3 did not exhibit antinociceptive activity to any
      significant extent.

PMID- 9142560
TI  - A study of structure of phenomenology of consciousness in meditative and non
      meditative states.
AB  - Twelve senior Kundalini (Chakra) meditators were assessed during meditation
      session and non-meditation or control session using Phenomenology of
      Consciousness Inventory. The data has been analyzed using structural analysis to
      measure the altered state of consciousness and the identity state by comparing
      meditative state with non-meditative state. The structural analysis of pattern of
      consciousness during the meditative state revealed altered experience in
      perception (percentile rank PR = 90), meaning (PR = 82) and time sense (PR = 87),
      while positive affect dimension showed increased joy (PR = 73) and love (PR =
      67). The imagery vividness (PR = 72), self-awareness (PR = 77), rationality (PR =
      73) and arousal (PR = 69) were found to be structurally different from the
      ordinary state. With regards to identity state meditative experience was found to
      produce statistically significant changes in terms of intensity in meaning (P <
      0.05), time sense (P < 0.05), joy (P < 0.05), love (P < 0.05) and state of
      awareness (P < 0.01). Our results indicate that long term practice of meditation
      appears to produce structural as well as intensity changes in phenomenological
      experiences of consciousness.

PMID- 9142561
TI  - Visual evoked potentials in primary hypertension.
AB  - Functional integrity of sensory pathways in the brain has not been well
      documented in hypertension. It is suggested that vascular endothelial changes
      including hyalinisation during hypertension may lead to demyelination in the
      vulnerable areas of the brain. Since optic nerve is considered to be part of
      brain hence the present study was done to find out if visual pathways are
      involved in hypertension. Transient pattern reversal visual evoked potentials
      (VEPs) from 01, 02 scalp regions were recorded in 23 primary hypertensive
      patients and compared with 14 normotensive control. Of these, six patients showed
      delayed P1 latencies beyond 99% tolerance limit i.e. Mean + 3 SD of normal. The
      remaining 17 had latencies of all positive (P1-P3) and negative (N1-N3) waves
      comparable to those of the control group. Correlation Coefficient worked out,
      showed significant correlation between systolic BP and P1 latency in the control
      group only. No other parameter showed any correlation with P1 latency & amplitude
      in both the groups. These findings show that fluctuations of BP in normotensive
      subjects have correlation with P1 latency. This correlation ceased to exist in
      hypertensive patients and abnormality in P1 latency of VEP was detected in 26%
      cases.

PMID- 9142562
TI  - Respiratory function during warm-up exercise in athletes.
AB  - The theme of the present study is to stress the importance of duration of warm-up
      exercise on respiratory functions in athletes. Significant improvements in
      athletic performance was achieved due to warm-up exercise owing to increase in
      blood flow, muscle and core temperature. The optimum intensity and duration are
      required to bring about the desired warm-up. A close examination on respiratory
      functions and its relationship with exercise has not been studied extensively.
      The present investigation is to explore the various respiratory functions in
      relation to the intensity and duration in preadolescent athletes before and after
      warm-up exercise. The results show a significant increase in vital capacity after
      25 min and a significant reduction in FEV0.5, FEF75% and FEF25-75% after 45 min
      of warm-up exercise. The results suggest that a warm-up exercise of short
      duration (25 min) and mild intensity was beneficial than long duration (45 min)
      and intense exercise. Although the performance of athletes was not directly
      measured during exercise, these data demonstrate the benefit of warm-up.

PMID- 9142563
TI  - Interaction of ciprofloxacin with diclofenac and paracetamol in relation to it's
      epileptogenic effect.
AB  - A number of fluoroquinolones have shown convulsive potential. The effect of
      Ciprofloxacin was studied in electroconvulsive seizures in mice using the tonic
      extensor phase as end point and seizure threshold as observational parameter. Its
      interaction with diclofenac and paracetamol was also studied. It was found that
      Ciprofloxacin produced a significant epileptogenic effect. This was potentiated
      by diclofenac but paracetamol had no such effect. Though the exact mechanisms
      involved in this effect are conjectural, role of GABA inhibitory mechanisms is a
      possibility.

PMID- 9142564
TI  - Total serum levels of triiodothyronine (T3) thyroxine (T4) and thyrotropine (TSH)
      in school going children of Dibrugarh district: an endemic goitre region of
      Assam.
AB  - The Thyroid Status was studied by estimating the total serum levels of T3 and T4
      by radioimmunoassay (RIA) and TSH by radioimmunometric Assay (IRMA) from 635
      school children (8-20 years; male 129, female 506) of the Dibrugarh district: a
      chronic endemic goitrous region of India. The results were compared with the
      control group of 147 (male 48, female 99) of healthy medical students of the same
      geographical area. The average values of T3 and TSH of school children were found
      higher and T4 lower than the control; the difference were only significant for T3
      and TSH. T3/T4 ratio is more in school children than the control. The findings of
      low T4 and high TSH indicate that the school children (Pubertal stage) from
      chronic iodine deficients areas suffer from poor thyroid status; the male seemed
      to have been affected more than the female. As age advances the thyroid status
      improves in female.

PMID- 9142565
TI  - Reduced toxicity and enhanced antitumor efficacy of betacyclodextrin plumbagin
      inclusion complex in mice bearing Ehrlich ascites carcinoma.
AB  - Inclusion complex of plumbagin was prepared with betacyclodextrin employing
      neutralization method. The toxicity of the drug was reduced and the antitumor
      efficacy was enhanced on complexation with betacyclodextrin.

PMID- 9142566
TI  - Intravenous glucose tolerance test in Macaca radiata radiata.
AB  - A reliable method for performing sensitive intravenous glucose tolerance tests in
      monkeys has been standardized. This helps in assessment of beta cell function. A
      normal curve for glucose disposal is constructed. A high variability in insulin
      levels is also documented.

PMID- 9142567
TI  - A combination of focusing and defocusing through yoga reduces optical illusion
      more than focusing alone.
AB  - The degree of optical illusion was assessed using standard Muller-Lyer lines in
      two groups (yoga and control) of thirty subjects each. All subjects were between
      eighteen and forty two years of age. The difference between the reading at which
      the lines were actually equal and the reading at which the subject felt them to
      be equal, was noted as the degree of illusion ("di"). Each subject was assessed
      at the beginning and end of a month. During the month the yoga group received
      training in yoga, while the control group carried on with their usual routine. At
      the end of the month the yoga group showed a significant (two factor ANOVA, Tukey
      test, P < .001) decrease in the "di" (86%), whereas the control group showed no
      change. The improvement following yoga could be attributed to the combination of
      focusing and defocusing involved in yoga practice, as these factors are known to
      influence the "di". Previous results which mentioned a 79% decrease in "di" with
      focusing alone, provided a comparison.

PMID- 9142569
TI  - Association of haptoglobin types with arterial blood pressure.

PMID- 9142568
TI  - Effects of oxyphenonium bromide and some antihistaminics (H1) on salivary flow in
      human volunteers.

PMID- 9142570
TI  - Dicrotic wave and anthropometry.

PMID- 9142571
TI  - Need for antidote for aluminium phosphide poisoning.

PMID- 9142572
TI  - Risk prediction: judging the judges.

PMID- 9142573
TI  - Platelet-neutrophil interactions in sepsis--platelet guilt by association?

PMID- 9142574
TI  - Growth hormone and insulin-like growth factors in critical illness.

PMID- 9142575
TI  - Platelet function in septic multiple organ dysfunction syndrome.
AB  - OBJECTIVE: Altered platelet function plays a role in the pathophysiology of
      multiple organ failure in sepsis. The purpose of the present study was to
      evaluate various aspects of platelet adhesive function in septic patients and its
      putative relevance for prognosis. DESIGN: Prospective clinical study. SETTING:
      Intensive Care Unit of the University Hospital. PATIENTS AND METHODS: A total of
      41 patients admitted to the medical Intensive Care Unit were studied. On the day
      of admission, patients were evaluated by intensive care scoring systems (Elebute,
      APACHE II) to assess the severity of sepsis and multiple organ dysfunction
      syndrome (MODS), and platelet function tests were performed. All patients were
      observed for 28 days to assess their clinical outcomes. Eleven patients revealed
      septicemia without MODS (Elebute > or = 12, APACHE II < 20) and 20 septic
      patients suffered from MODS (Elebute > or = 12, APACHE II > or = 20). Ten non
      septic patients without MODS served as a control group (Elebute < 12, APACHE II <
      20). Flow cytometric determination of the activated fibrinogen (fg) receptor
      GPIIb-IIIa and as well as thrombospondin (TSP) on platelets and platelet
      neutrophil adhesion (CD 41 immunofluorescence) ex vivo was performed using
      monoclonal antibodies. The effect of plasma obtained from patients on normal
      platelet aggregation in vitro, and adhesion to cultured endothelial cells was
      evaluated. RESULTS: The surface expression of TSP on platelets was increased in
      septic patients with MODS compared to controls (p < 0.03). Platelet-neutrophil
      adhesion was not significantly altered in septicemia (p < 0.09) but decreased
      significantly in the presence of MODS (p < 0.05) when compared to controls.
      Logistic regression analysis showed that platelet-neutrophil adhesion was an
      independent predictor for poor clinical outcome (p < 0.01). Plasma from septic
      patients sensitized normal platelets to hyperaggregate and to adhere to cultured
      endothelium (p < 0.01). CONCLUSION: In septic patients platelets become activated
      and are hyperadhesive to other vascular cells including neutrophils and
      endothelium. This may induce sequestration of platelets and microcirculatory
      arrest, thus the development of MODS.

PMID- 9142576
TI  - A non-derivative, non-surgical tracheostomy: the translaryngeal method.
AB  - OBJECTIVE: To present a new technique for non-surgical tracheostomy. DESIGN: An
      open, clinical trial on patients requiring elective tracheostomy. SETTING:
      Intensive care unit of a community hospital. PATIENTS: 95 adults, mean age 60
      years, and 14 infants and children, mean age 26 months (2 months-7 years) with
      common indications for tracheostomy. INTERVENTION: Through a needle inserted in
      the trachea, a guidewire is pushed out of the mouth against the usual direction
      and attached to a special device formed by a flexible plastic cone with a pointed
      metal tip joined to an armoured tracheal cannula. This device is then pulled back
      through the oral cavity, larynx and trachea and outwards across the neck wall by
      the operator applying traction on the wire with one hand and counterpressure on
      the neck wall with the fingers of the other hand. When the cone and a part of the
      cannula have emerged, the cannula is cut off from the cone, straightened
      perpendicular to the skin, rotated and advanced caudally to its final position.
      RESULTS: The cone-cannula passed smoothly through the vocal cords. The metallic
      point perforated the neck easily. The dilation did not present any risk of
      tracheal wall damage because the direction of the manoeuvre was from the inside
      to the outside of the neck. The tissues tightly adhered to the cannula, thus
      avoiding infection and bleeding. The use of ventilation systems permitted
      utilization of translaryngeal tracheostomy (TLT) even in patients for whom apnoea
      might have carried some risk, because there is no interruption of respiratory
      assistance during the procedure. Follow-up showed no late obstructive
      complication at the level of the tracheostoma. CONCLUSIONS: By virtue of its
      greater safety and less trauma to tissues than percutaneous techniques, TLT can
      also be carried out in infants and children (an important benchmark for any
      tracheostomy technique) and in very difficult patients from whom other techniques
      have serious drawbacks.

PMID- 9142577
TI  - Ultrasonographic bedside evaluation of maxillary sinus disease in mechanically
      ventilated patients.
AB  - OBJECTIVE: Evaluate A-mode ultrasonographic examination of maxillary sinus
      disease in mechanically ventilated, critically ill patients using sinoscopy as
      criterion standard. DESIGN: Prospective case series. SETTING: The intensive care
      units of a tertiary care hospital. PATIENTS: 25 mechanically ventilated,
      critically ill patients with nasotracheal intubation or a tracheotomy were
      followed up by ultrasonographic examination of the maxillary sinuses in supine
      and semirecumbent positions. Infectious sinusitis was suspected in 15 patients,
      who were bilaterally sinoscoped combined with sampling for bacterial culture.
      RESULTS: The frequency of oedema and/or secretions was high: 29 antra of 30
      examined. Only 2 of 30 antra showed bacterial infection. Ultrasonographic
      examinations were sensitive to general pathological changes but less accurate in
      specific diagnostics such as the presence of secretions (sensitivity for fluid
      75%, oedema 81%). The sensitivity of ultrasonographic diagnosis improved when the
      examination was made in the semirecumbent position (sensitivity for fluid 91%,
      oedema 81%). CONCLUSIONS: A-mode ultrasonography is a useful method for daily
      use, being easy to perform and without discomfort to the patient. It is fast and
      gives an immediate diagnosis. In intensive care unit patients, it should be the
      method of choice for day-to-day studies of effects and changes in the upper
      airways. For the differential diagnosis of oedema and/or secretions, it is not
      reliable enough to be used as the sole diagnostic method. A complementary
      investigation, such as computed tomography or sinoscopy, which also provides the
      opportunity to take samples, is needed for diagnostic confidence.

PMID- 9142578
TI  - Unfavorable mechanical effects of heat and moisture exchangers in ventilated
      patients.
AB  - OBJECTIVE: To investigate the mechanical effects of artificial noses. SETTING: A
      general intensive care unit of a university hospital. PATIENTS: 10 patients in
      pressure support ventilation for acute respiratory failure. INTERVENTIONS: The
      following three conditions were randomly tested on each patient: the use of a
      heated humidifier (control condition), the use of a heat and moisture exchanger
      without filtering function (HME), and the use of a combined heat and moisture
      exchanger and mechanical filter (HMEF). The pressure support level was
      automatically adapted by means of a closed-loop control in order to obtain
      constancy, throughout the study, of patient inspiratory effort as evaluated from
      airway occlusion pressure at 0.1 s (P0.1). Patient's ventilatory pattern, P0.1,
      work of breathing, and blood gases were recorded. MEASUREMENTS AND MAIN RESULTS:
      The artificial noses increased different components of the inspiratory load:
      inspiratory resistance, ventilation requirements (due to increased dead space
      ventilation), and dynamic intrinsic positive end-expiratory pressure (PEEP). The
      additional load imposed by the artificial noses was entirely undertaken by the
      ventilator, being the closed-loop control of P0.1 effective to maintain constancy
      of patient inspiratory work by means of adequate increases in pressure support
      level. CONCLUSIONS: The artificial noses cause unfavorable mechanical effects by
      increasing inspiratory resistance, ventilation requirements, and dynamic
      intrinsic PEEP. Clinicians should consider these effects when setting mechanical
      ventilation and when assessing patients' ability to breathe spontaneously.

PMID- 9142579
TI  - Radiographic detection of intrabronchial malpositions of nasogastric tubes and
      subsequent complications in intensive care unit patients.
AB  - OBJECTIVE: The aim of our study was to illustrate the radiographic spectrum of
      the intrabronchial malposition of nasogastric tubes and subsequent complications,
      and to discuss the role of radiography in the detection of such malpositions.
      DESIGN: Retrospective clinical investigation. SETTING: Tertiary care university
      teaching hospital. PATIENTS AND METHODS: We reviewed chest radiographs of 14
      intensive care patients with nasogastric tubes malpositioned in the
      tracheobronchial tree. The site and anatomic location of the malposition were
      recorded. Complications due to tube malpositioning were monitored on follow-up
      radiographs and on computed tomographic examinations, which were available in 4
      patients. RESULTS: Nine of 14 nasogastric tubes were inserted in the right and 5
      in the left tracheobronchial tree. Tube tips were malpositioned in the lower lobe
      bronchi (50%), the intermediate bronchus (36%), and the main bronchi (14%). There
      was perforation of the bronchial system with subsequent pneumothorax in 4
      patients. In 4 other patients, pneumonia developed at the former site of the
      malpositioned tube tip. Radiographic detection of nasogastric tube malpositioning
      was prompt in 9 patients and delayed in 5 patients. CONCLUSIONS: Whereas clinical
      signs of nasogastric tube malpositioning in intensive care patients may be absent
      or misleading, chest radiography can accurately detect nasogastric tube
      malpositions in the tracheobronchial tree, may prevent complications, and avoid
      the use of further costly or invasive diagnostic techniques.

PMID- 9142580
TI  - Relation of echocardiographic preload indices to stroke volume in critically ill
      patients with normal and low cardiac index.
AB  - OBJECTIVE: To examine the usefulness of preload indices obtained by
      transoesophageal echocardiography (TOE) for estimating stroke volume at various
      levels of cardiac index. DESIGN: Prospective clinical study. SETTING: Intensive
      care unit with surgical patients. PATIENTS: 16 ventilated patients monitored via
      Swan-Ganz catheterization and TOE. INTERVENTIONS: Echocardiographic images of
      left ventricular cross-sectional short-axis areas were analysed for the preload
      indices end-diastolic area (EDA), stroke area and end-diastolic wall stress. The
      relation between these indices and stroke volume, calculated from thermodilution
      cardiac output, was analysed in all patients and in nine patient groups
      discriminated by various ranges in heart rate (< or = 70 to > 110 beats/min),
      pulmonary artery occlusion pressure (< or = 8 to > 12 mmHg) and cardiac index (<
      or = 3.0 to > 4.2 l/min per m2). MEASUREMENTS AND RESULTS: Overall stroke volume
      (n = 155) correlated significantly (p < 0.0001) with EDA (r = 0.89) and stroke
      area (r = 0.80). The correlation with end-diastolic wall stress was non
      significant (r = 0.51). Linearity in the relation between stroke volume and EDA
      or stroke area was independent of variations in heart rate and pulmonary artery
      occlusion pressure. Stroke volume correlated well with EDA and stroke area, when
      cardiac index was normal or high, but the relation slightly deteriorated (r =
      0.63 to < or = 0.72) when the cardiac index was low. Changes in EDA and stroke
      area by more than 1, 2 or 3 cm2 were weak predictors for changes in stroke volume
      greater than 20%. CONCLUSIONS: Stability of the relation between
      echocardiographic preload indices and stroke volume emphasize the potential of
      TOE for continuous preload monitoring in the critically ill.

PMID- 9142581
TI  - Reliability of anion gap as an indicator of blood lactate in critically ill
      patients.
AB  - OBJECTIVE: To evaluate the sensitivity, specificity, and predictive values of an
      elevated anion gap as an indicator of hyperlactatemia and to assess the
      contribution of blood lactate to the serum anion gap in critically ill patients.
      DESIGN: Prospective study. SETTING: General intensive care unit of a university
      hospital. PATIENTS: 498 patients, none with ketonuria, severe renal failure or
      aspirin, glycol, or methanol intoxication. MEASUREMENTS AND RESULTS: The anion
      gap was calculated as [Na+]-[Cl-]-[TCO2]. Hyperlactatemia was defined as a blood
      lactate concentration above 2.5 mmol/l. The mean blood lactate concentration was
      3.7 +/- 3.2 mmol/l and the mean serum anion gap was 14.3 +/- 4.2 mEq/l. The
      sensitivity of an elevated anion gap to reveal hyperlactatemia was only 44% [95%
      confidence interval (CI) 38 to 50], whereas specificity was 91% (CI 87 to 94 and
      the positive predictive value was 86% (CI 79 to 90). As expected, the poor
      sensitivity of the anion gap increased with the lactate threshold value, whereas
      the specificity decreased [for a blood lactate cut-off of 5 mmol/l: sensitivity =
      67% (CI 58 to 75) and specificity = 83% (CI 79 to 87)]. The correlation between
      the serum anion gap and blood lactate was broad (r2 = 0.41, p < 0.001) and the
      slope of this relationship (0.48 +/- 0.026) was less than 1 (p < 0.001). The
      serum chloride concentration in patients with a normal anion gap (99.1 +/- 6.9
      mmol/l) was comparable to that in patients with an elevated anion gap (98.8 +/-
      7.1 mmol/l). CONCLUSIONS: An elevated anion gap is not a sensitive indicator of
      moderate hyperlactatemia, but it is quite specific, provided the other main
      causes of the elevated anion gap have been eliminated. Changes in blood lactate
      only account for about half of the changes in anion gap, and serum chloride does
      not seem to be an important factor in the determination of the serum anion gap.

PMID- 9142582
TI  - Advantage of buffered solutions or automated capnometry in air-filled balloons
      for use in gastric tonometry.
AB  - OBJECTIVE: To test accuracy, reproducibility and time constants of pCO2
      measurement with the tonometric technique, using different media for filling the
      silastic balloon (saline, phosphate buffer, citrate buffer, air) and employing
      different analyzer devices (ABL3, ABL330, Nova Stat 5, automated capnometry).
      DESIGN: Comparative laboratory study of different tonometric techniques,
      measuring test solutions with known pCO2 values due to pre-equilibration with
      three different pCO2 concentrations. SETTING: Clinical laboratory of a university
      hospital intensive care unit. MEASUREMENTS AND RESULTS: The use of saline, as
      suggested for routine tonometry, led to negative bias values throughout, i.e.
      underestimation of pCO2 values, the extent of which depended on the blood gas
      analyzer device employed. Registration of the equilibration kinetics showed that
      full equilibration demanded 90 min regardless of the environmental pCO2 level.
      Replacing saline by buffered electrolyte solutions resulted in a significant
      improvement of bias, but did not change the kinetics of pCO2 equilibration. The
      employment of air-filled balloons, combined with automated capnometry, led to
      very low bias values, approaching zero, for all pCO2 levels, along with excellent
      precision. Time constants of equilibration were dramatically reduced, with full
      equilibration being achieved within 12.5 min. CONCLUSIONS: Buffered electrolyte
      solutions are preferable to saline for achieving reliable pCO2 measurements in
      gastric tonometry. Air-filled balloons, combined with automated capnometry,
      present excellent accuracy and reproducibility together with short equilibration
      times, thus offering "on-line" monitoring of even rapid changes in environmental
      pCO2.

PMID- 9142583
TI  - Use of 2% propofol to produce diurnal sedation in critically ill patients.
AB  - OBJECTIVE: The assessment of propofol to produce diurnal sedation in critically
      ill patients. DESIGN: Prospective clinical study. SETTING: Intensive Care Unit,
      University Hospital. PATIENTS AND PARTICIPANTS: Thirty consecutive patients
      admitted to the Intensive Care Unit older than 18 years who were expected to be
      sedated for more than 50 h. INTERVENTIONS: The patients were randomised into two
      groups. All received sedation with a constant background infusion of morphine and
      a variable infusion rate of propofol, which was altered hourly to maintain the
      intended sedation score. The first group received constant light sedation (CLS)
      over 50 h aiming for a Ramsay score of 2-3. The second group received CLS between
      0600 h and 2200 h and additional night sedation (ANS) with propofol between 2200
      h and 0600 h, aiming for a sedation score of 4-5. MEASUREMENTS AND RESULTS:
      Patients were studied for 50 h from 1800 h on the first day of admission.
      Recordings of heart rate, blood pressure, sedation scores and propofol and
      morphine infusion rates were made hourly. An APACHE II score was recorded for
      each patient. Sedation scores were analysed by blind visual assessment and
      cosinor analysis, which is used in chronobiology to examine the correlation of
      data with a cosine curve. Patients in the ANS group had significantly better
      rhythmicity of sedation levels using cosinor analysis (r = 26% v 8%) p < 0.01.
      There was no difference between the CLS and ANS groups with respect to age, sex
      or APACHE II scores. Nine out of 15 patients in the ANS group achieved diurnal
      sedation. Three patients in the CLS group showed diurnal rhythmicity of sedation,
      which can be attributed to natural sleep, and had a median APACHE II score of 12.
      Five patients in the CLS group and three in the ANS group showed a deep constant
      sedation pattern. They had high APACHE II scores (median 21.5) and an obtunded
      conscious level on admission due to severe sepsis. CONCLUSION: Propofol can
      safely provide diurnal sedation in the critically ill when titrated against the
      Ramsay score. Sedation levels cannot be manipulated in some severely ill
      patients.

PMID- 9142584
TI  - Informed consent for research purposes in intensive care patients in Europe--part
      II. An official statement of the European Society of Intensive Care Medicine.
      Working Group on Ethics.

PMID- 9142585
TI  - Pneumothorax following nasogastric feeding tube insertion in a tracheostomized
      patient after bilateral lung transplantation.
AB  - We report the case of a pneumothorax caused by the improper placement of a
      nasogastric feeding tube in a tracheostomized patient after bilateral lung
      transplantation. We discuss the contribution of low-pressure cuffed tracheostomy
      tubes to the inadvertent respiratory tract misplacement of a nasogastric feeding
      tube, as well as the problems of nasogastric feeding tube insertion in the
      sedated patient, why the previously installed closed-tube thoracostomy did not
      prevent the pneumothorax and possible pitfalls in confirming the proper position
      of the nasogastric feeding tube. In conclusions, we stress that in high risk
      patients a nasogastric feeding tube should only be inserted under direct vision
      and that a subsequent routine X-ray is mandatory for confirming proper
      positioning.

PMID- 9142586
TI  - Major cellulitis following percutaneous tracheostomy.
AB  - Percutaneous tracheostomy, a technique that can be performed at the bedside in
      the intensive care unit (ICU), is increasingly used for critically ill ventilator
      dependent patients. Based on many clinical studies, this procedure appears to be
      simple, rapid and safer than conventional surgical tracheostomy. This technique
      produces a stoma tissue tract that fits snugly around the cannula, and this could
      explain the low incidence of infective complications. However, we report two
      cases of life-threatening cellulitis, a serious complication that has rarely been
      reported previously.

PMID- 9142587
TI  - Endoscopic placement of a tracheal oxygen catheter: a new technique.
AB  - OBJECTIVE: In patients with chronic obstructive pulmonary disease (COPD),
      intratracheal oxygen insufflation (ITO) is an established therapeutic approach.
      We developed a new endoscopic technique of intratracheal catheter placement. The
      aim of this pilot study was to demonstrate its short-term feasibility in acutely
      extubated patients with moderate to severe COPD who require oxygen therapy.
      DESIGN: A guide wire was inserted through a nasally passed bronchoscope and was
      positioned such that its tip was placed intratracheally. Using a "Seldinger
      technique", the tracheal catheter was then inserted over the wire to a point 2-3
      cm proximal to the carina and positioned under direct vision from the
      bronchoscope inserted through the contralateral nose. After catheter insertion,
      the guide wire was removed. The patients scored catheter-associated local
      discomfort using a visual analogue scale. In a randomly assigned, crossover
      design, the effectiveness of the endoscopically (e) inserted ITO catheter was
      assessed by measuring the capillary blood gases, respiratory rate (RR), tidal
      volume (Vt) and minute ventilation (MV) after 1 h breathing room air without eITO
      and 1 h after eITO (flow: 3 l/min). MEASUREMENTS AND RESULTS: The eITO catheter
      was placed in all patients without complications and with only minimal discomfort
      in two patients (spontaneously reversible cough). Compared to breathing room air,
      capillary O2 pressure increased (from 54.7 +/- 9.4 to 82.8 +/- 21.8 mmHg) whereas
      Vt (from 458.7 +/- 86.8 to 358.3 +/- 75.1 ml) and MV (from 7.7 +/- 1.5 to 5.5 +/-
      1.1 l/ min) decreased significantly (each p < 0.0001) with eITO in all patients.
      The capillary CO2 pressure and RR did not change. CONCLUSIONS: Acutely extubated
      patients in whom oxygen therapy is indicated may profit from eITO. This new
      technique works immediately and is thus an effective short-term intervention of
      potential value in the intensive care unit.

PMID- 9142588
TI  - Generation of nitrogen dioxide during nitric oxide therapy and mechanical
      ventilation of children with a Servo 900C ventilator.
AB  - OBJECTIVE: To determine the combinations of nitric oxide (NO), oxygen (O2),
      minute ventilation (MV) and total gas flow (TGF) which generate toxic
      concentrations of nitrogen dioxide (NO2) during mechanical ventilation with a
      Servo 900C ventilator. DESIGN: The measurement of NO2 generated with NO (20, 40,
      60, 80, 100 ppm) and O2 [fractional inspired oxygen (FIO2) 0.21, 0.4, 0.6, 0.9]
      during mechanical ventilation with MVs of 2.5, 5.0 and 7.5 l/min and TGFs from 2
      to 14 l/min. SETTING: Laboratory of intensive care unit in paediatric tertiary
      hospital. RESULTS: Toxic concentrations of NO2 (> 5 ppm) were generated in the
      ventilator circuit when NO was 80 ppm or 100 ppm in FIO2 of 0.6 or 0.9 with MVs
      of 2.5, 5.0 and 7.5 l/ min; and with 80 ppm NO in FIO2 of 0.6 at all TGFs from
      2.0 to 13.6 l/min and MVs of 2.5, 5.0 and 7.5 l/min (TGF/MV 0.3-5.4). NO2 1.5-2.6
      ppm was generated with 40 ppm NO in FIO2 of 0.6, TGFs 2.1-13.7 l/ min, and MVs
      2.5, 5.0 and 7.5 l/min (TGF/MV 0.3-5.5). NO2 0.9-0.6 ppm was generated with 20
      ppm NO in FIO2 of 0.6, TGFs 2.5-13.8 and MVs 2.5, 5.0 and 7.5 (TGF/MV 0.3-5.5).
      NO2 generation was not affected significantly by the TGF/MV ratio. CONCLUSIONS:
      The generation of NO2 in the ventilator circuit is directly proportional to
      concentration of NO and O2 and inversely proportional to the TGF and MV but
      uninfluenced by the TGF/MV ratio. NO 80 ppm, but neither 20 nor 40 ppm in FIO2 of
      0.6, generates toxic NO2 irrespective of TGF, MV or the TGF/MV ratio.

PMID- 9142589
TI  - Surfactant nebulisation: safety, efficiency and influence on surface lowering
      properties and biochemical composition.
AB  - OBJECTIVE: The objectives of this study were, to select a nebuliser first, that
      operates safely in a neonatal ventilator setting and, second, that is most
      efficient. Thirdly, we studied the particle sizes of the surfactant aerosol.
      Fourthly, we studied where the nebulised surfactant is deposited in the tubing
      system of the ventilator. Finally, we studied whether nebulisation influences the
      composition and biophysical properties of surfactant. MEASUREMENTS AND RESULTS:
      Safety was assessed by measuring "mean airway pressures" in a test lung before,
      during and after surfactant nebulisation, for three jet nebulisers. The MiniNEB
      did not alter these pressures, and is thus safe, whereas the other two nebulisers
      (Intersurgical and Flo-Thru) increased these pressures. The efficiency of
      nebulisation was assessed by measuring the amount of phospholipid deposited in
      the test lung. The MiniNEB showed the highest efficiency: 10% versus 1-3% of the
      other two nebulisers. The particle sizes of surfactant aerosol were assessed by
      the laser diffraction method. Seventy percent of the particles were 1-5 microns.
      The deposition of surfactant aerosol in the tubing system was assessed by
      nebulising surfactant that was labelled with 99mTc Nanocoll. Afterwards the
      tubing system was imaged using a gamma camera. The majority of surfactant was
      deposited in the expiratory hose (28%), nebuliser (20%), Y-piece (16%) and
      expiratory filter (12%). Finally the phospholipid composition, spreading
      velocity, static and dynamic surface tensions were assessed for the nebulised
      surfactant and compared to the stock surfactant. In addition, nebulised
      surfactant was instilled in premature rabbits and tidal volumes were measured to
      assess the dose-response relation. We found that neither the composition nor
      biophysical properties had been altered by nebulisation. CONCLUSIONS: The MiniNEB
      nebulised surfactant safely in a neonatal ventilator setting with respect to
      airway pressures. The efficiency of nebulisation is low: the majority of the
      surfactant aerosol is deposited in the expiratory tubing. The surfactant
      composition and function is not altered by nebulisation. Therefore the
      nebulisation of surfactant is feasible, but efforts should be made to improve the
      efficiency of this procedure.

PMID- 9142590
TI  - Lower respiratory rates without decreases in oxygen consumption during neonatal
      synchronized intermittent mandatory ventilation.
AB  - OBJECTIVE: We tested the hypothesis that synchronization to patient effort during
      intermittent mandatory ventilation (SIMV), when compared to conventional
      unsynchronized intermittent mandatory ventilation (IMV), will decrease energy
      expenditure, as reflected by decreased oxygen consumption (VO2). DESIGN: We used
      a four-period crossover design. Each patient was studied over four 30-min
      continuous time intervals. Patients were randomized to receive initially IMV or
      SIMV, then crossed over such that each patient was treated twice with each
      modality. Data were analyzed using an analysis of variance technique. SETTING:
      Patients were receiving treatment in the newborn intensive care unit of
      Children's Hospital, St. Paul. PATIENTS: We studied 17 patients, who ranged from
      23 to 37 weeks gestation, were < or = 14 days old, and had study weights from 623
      to 3015 g. All were mechanically ventilated for hyaline membrane disease.
      MEASUREMENTS AND RESULTS: We measured and compared VO2, carbon dioxide
      consumption (VCO2), minute ventilation (VE), total respiratory rate, heart rate,
      arterial blood pressure, and arterial oxygen saturation (SaO2) values during IMV
      and SIMV. Total respiratory rate fell significantly during SIMV (73 +/- 26 during
      IMV, 57 +/- 17 during SIMV, p < 0.01) in spite of no significant change in VO2
      (0.6 +/- 0.16% fall in VO2 during SIMV) or VCO2 (4.2 +/- 0.19% increase in VCO2
      during SIMV) values. Moreover, there were no significant differences in heart
      rate, blood pressure, VE, or SaO2 values with either form of therapy.
      CONCLUSIONS: Though total respiratory rate fell, these data do not support the
      hypothesis that SIMV significantly reduces respiratory rate by decreasing oxygen
      consumption and carbon dioxide production during infant mechanical ventilation.
      Rather, the marked fall in respiratory rate may be due to a more efficient
      respiratory pattern.

PMID- 9142592
TI  - Summary of round table conference: gut dysfunction in critical illness.
AB  - There is recent evidence that intestinal function is an important determinant in
      the outcome of critically ill patients. The barrier function is an important
      characteristic of the gut. Its workings are complex and it consists of
      epithelial, molecular, and immune components. The pathogenesis of gut dysfunction
      among critically ill patients is multifactorial, consisting of the quality and
      quantity of microorganisms, the permeability of the epithelium, and the extent of
      the vascular perfusion. A practical bedside measure of gut dysfunction is
      intolerance to enteral feedings. Potential therapies for gut dysfunction include
      the use of vasoactive drugs to enhance perfusion, selective decontamination to
      decrease bacteria and endotoxin, and the early and frequent administration of
      enteral nutrients.

PMID- 9142591
TI  - Quantitative estimation of errors in the indicator dilution measurement of
      extravascular lung water.
AB  - OBJECTIVE: To assess the accuracy of the diffusible indicators heavy water and
      thermal indicator in the measurement of extravascular lung water (EVLW). DESIGN:
      Cardiac output (CO), mean transit time and EVLW for the two diffusible indicators
      were measured. CO for indocyanine green, gravimetric EVLW and the calculated mean
      transit time for a diffusible indicator were used as independent reference
      variables. CO, mean transit time and EVLW for the two diffusible indicators were
      compared to the reference variables and the percentage error for each measured
      variable was calculated for each bolus injection. SETTING: 6 sheep with healthy
      lungs and 6 with pulmonary oedema in a research laboratory. INTERVENTIONS: CO was
      altered with positive end-expiratory pressure and dobutamine. MEASUREMENTS: All
      indicators were given together in a bolus through a central venous line.
      Indicators were detected simultaneously in the aorta, and CO, mean transit time
      and EVLW were measured. EVLW was measured gravimetrically (EVLWgrav) postmortem.
      RESULTS: In the combination of a low CO and a large distribution volume, heavy
      water and thermal indicator produced a large number of slow wash-out curves.
      These curves were abolished from further analysis. The mean errors in CO and mean
      transit time for heavy water were close to zero and independent of the
      distribution volume; the product EVLW was close to EVLWgrav. The mean error in
      thermodilution CO measured in the aorta was close to zero but dependent on the
      distribution volume. The mean error in mean transit time for the thermal
      indicator was 36% and dependent on the distribution volume. Their product EVLW
      overestimated EVLWgrav by 70%. CONCLUSIONS: The results obtained for heavy water
      confirmed the theoretical basis of the indicator dilution method. The mean
      transit time for the thermal indicator was not proportionate to its distribution
      volume. The magnitude of this error prevents the calculation of an anatomically
      defined EVLW using a catheter-mounted thermistor in the aorta.

PMID- 9142593
TI  - Hyponatraemic coma after ecstasy ingestion.

PMID- 9142594
TI  - Neuroleptic malignant syndrome following tricyclic antidepressant overdose.

PMID- 9142595
TI  - Relationship between pulmonary oxygen consumption, lung inflammation, and
      calculated venous admixture in patients with acute lung injury.

PMID- 9142596
TI  - Cisapride in reducing postoperative gastrocaecal transit time after cardiac
      surgery in children.

PMID- 9142597
TI  - Validation of a quality of life questionnaire for critically ill patients.

PMID- 9142598
TI  - In pursuit of "growth with equity": the limits of Chile's free-market social
      reforms.
AB  - The economic and social strategy developed by the democratic governments in Chile
      since 1990 has been based on the premise that free-market policies promoting
      growth and economic stability must continue, but should be combined with social
      policies designed to promote greater equality. This new set of policies produced
      quick and positive results in the context of strong economic growth. The
      reduction of poverty was its crowning achievement. However, not all the
      Concertacion's redistributive efforts have enjoyed the same level of success.
      Inequalities in income distribution are again increasing. Significant segments of
      society, such as subsistence farmers, rural migrants to cities, women and youth
      who lack vocational training--as well as an important segment of the middle class
      that had been impoverished during the military regime--are being systematically
      marginalized from the benefits of economic growth and social policy. The
      fundamental problems of current Chilean social policy are rooted in the
      privatization of social sectors under the military government and the resulting
      dual model of social welfare.

PMID- 9142599
TI  - World Bank education policy: market liberalism meets ideological conservatism.
AB  - Neoliberalism does not consider education a strategic investment. World Bank
      discourse for Latin America lacks a medium- and long-term view and is based on a
      short-term cost-benefit analysis. The Bank's education policy is determined by
      "adjustment" of countries economies so that they can go on paying their external
      debts. The goal is to eliminate educational expenses for the states by keeping
      education for elites, breaking up and privatizing the large public education
      systems, and nullifying teachers' contracts. To justify its policy, the Bank
      argues that governments should stop financing secondary and higher education and
      instead focus on primary education, where investments would be more efficient.
      But at the same time, governments should shift the financing of primary education
      to the private sector. Teachers' unions are now at the forefront of opposition to
      the World Bank's education reforms.

PMID- 9142600
TI  - Unhealthy cities: corporate medicine, community economic underdevelopment, and
      public health.
AB  - The growing corporate dominance in U.S. medical care has been a major factor in
      the increasingly inequitable distribution of health care resources and the
      declining public health conditions in poor and minority urban communities.
      Alongside this trend has been a parallel phenomenon of economic disinvestment and
      political neglect in these same at-risk neighborhoods. This article analyzes
      these trends as related components of austerity, retrenchment, and capital
      consolidation policies that have characterized the U.S. political economy for
      several decades. Emphasized are the relationships among corporatization, capital
      consolidation, deindustrialization of the workforce, and medical indigence; the
      resulting economic stress placed upon community hospitals and other caregivers in
      poor and minority communities; and the marked discrepancy between conditions of
      development and underdevelopment in American cities. It is argued that the
      effects of these policies are pathogenic in nature: they place populations at
      risk for disease and social dysfunction, they reduce access to necessary
      preventive and curative services, and they weaken coping mechanisms. Community
      economic development, empowerment, and a direct challenge to the growing
      concentration of wealth and power in the corporate class are proposed as
      essential elements of public health policy.

PMID- 9142601
TI  - The roast beef of old England.
AB  - The author examines the origins of the "mad cow" crisis in Britain, identifying
      the responsibility of the Conservative government with its policy of
      deregulation, and details government attempts to "cover up" the problem and to
      prevent discussion of the question of responsibility by conducting a campaign of
      anti-Europeanism. The possible public health consequences are considered.

PMID- 9142602
TI  - Preventive services in occupational health and safety in Europe: developments and
      trends in the 1990s.
AB  - This article outlines the legislative requirements for preventive services in
      health and safety in 13 European countries and considers the implementation and
      coverage of such services. The author identifies the predominant models of
      preventive services operating in the European Union, then assesses the influence
      of the E.U. Framework Directive 89/391 on the development and integration of
      preventive services and the role of workers in their organization and
      accountability. Significant differences exist in the extent and functions of
      preventive services in European countries, including differences in coverage
      between southern and northern European countries, different degrees to which
      employees in small enterprises and large enterprises are covered by preventive
      services, and overall differences in legislative approach.

PMID- 9142603
TI  - Agricultural pesticide use in developing countries: health effects and research
      needs.
AB  - Large worker populations in the Third World are exposed to increasing amounts of
      pesticides, including pesticides severely restricted and banned in industrialized
      countries. Studies on knowledge, attitudes, and practices indicate that unsafe
      use of pesticides is the rule in Third World countries. Surveys of acute
      poisonings show high rates in these countries, despite underregistration. The
      scarce studies on chronic health outcomes demonstrate neurotoxic, reproductive,
      and dermatologic effects. Exposure assessment consists mainly of cholinesterase
      testing, and few studies have quantified dermal and respiratory exposure. The few
      intervention studies demonstrate the need for evaluation of the impact of
      preventive measures and policies. There is no evidence that widespread "safe-use"
      programs have greatly affected exposure and morbidity. It was concluded that
      research should focus on simple methods for surveillance of exposure and on
      surveillance of acute illness and its causes in order to develop and evaluate
      rapid local interventions. Studies on chronic effects should be carried out in
      selected countries, aiming at long-term and broader interventions. Policies that
      promote the use of pesticides should be critically evaluated. North-South and
      South-South research collaborations must be encouraged to address this global
      health problem.

PMID- 9142605
TI  - Subjects and accomplices: regulation and the ethics of cigarette advertising.
AB  - In debates on the regulation of cigarette advertising, opposition to regulation
      is based on a perceived threat to individual autonomy and choice. Advocates of
      regulation have sought to combat such arguments by focusing on the unique
      characteristics of tobacco: the absence of a "safe" level of consumption; that
      the habit is often acquired by children or young persons; that smokers are
      unaware of the extent of the risks involved; and that smoking is "addictive." The
      authors discuss the implications of these characteristics for regulation and the
      difficulties with such arguments. The focus on characteristics of the product
      means that little attention is given to the implications of the content and
      techniques of advertising. The dominant forms of cigarette advertising involve
      the communication of little product information and the use of persuasive
      mechanisms of which the consumer is either unaware or not fully aware. The
      authors explore the implications of such advertising strategies for regulation
      and public policy.

PMID- 9142604
TI  - Does licensing of drugs in industrialized countries guarantee drug quality and
      safety for Third World countries? The case of norplant licensing in Finland.
AB  - Norplant implantable contraceptives were developed mainly for use in Third World
      countries, but first were approved for marketing in Finland in 1983 and in Sweden
      in 1985. Since then Norplant has been approved in more than 40 countries, most of
      them in the Third World. The authors analyzed the clinical documentation
      submitted to the Finnish and Swedish drug control authorities, and the
      assessments made of the data. The Finnish review process lasted for three years,
      and the number of data increased substantially during that time. The authors have
      not been allowed to publish the clinical data submitted in Finland, but a
      reconstruction from the Swedish data showed that the clinical data were of poor
      quality and were mainly focused on assessing efficacy. Side effects,
      acceptability, and requirements of the health care system for proper use of
      Norplant were poorly studied. This example of Norplant licensing in Finland shows
      that licensing of drugs in industrialized countries is insufficient for
      guaranteeing their safety in Third World countries.

PMID- 9142606
TI  - State-level clustering of safety measures and its relationship to injury
      mortality.
AB  - This article proposes a social model of investigating injury mortality. The
      authors hypothesize that (1) state-level laws and regulations on safety cluster
      together in one or more groupings; (2) groupings of safety measures play a
      significant role in injury mortality; and (3) injury mortality is very highly
      associated with social structural variables. There is a clustering of safety
      policies, with five factors explaining 67 percent of variance, although no
      "master factor" was discovered. The strongest factor, explaining 21 percent of
      variance, includes three gun laws and low speed limits before the 1973 federal
      law. One factor is the most global in that it taps three distinct areas,
      including helmet laws, minor blood alcohol levels, and smoke detectors, though it
      only explains 7.5 percent of variance. The only factor that remains in a
      regression for injury mortality is one that includes strong seat belt laws and
      strong enforcement of those laws, though in the direction opposite to that
      hypothesized. This factor, along with percentage rural and environmental spending
      per capita, is significant for both motor vehicle and non-motor vehicle
      mortality. For motor vehicle mortality alone, deaths are higher in states with
      higher percentages of Hispanics and fewer people receiving food stamps and AFDC.
      Many factors that usually predict individual injury mortality do not hold at the
      state level, suggesting the usefulness of looking at social factors for new
      insights into injury mortality and prevention.

PMID- 9142607
TI  - User fee policies to promote health service access for the poor: a wolf in
      sheep's clothing?
AB  - An international survey of health service user fee and exemption policies in 26
      low- and middle-income countries assessed whether user fee policies were
      supported by measures that protect the poor. In particular, it explored whether
      governments were introducing a package of supportive measures to promote service
      improvements that benefit disadvantaged groups and tackle differential ability to
      pay through an effective series of exemptions. The results show that many
      countries lack policies that promote access for disadvantaged groups within user
      fee systems and quality improvements such as revenue retention at the health care
      facility and expenditure guidelines for local managers. More significant policy
      failures were identified for exemptions: 27 percent of countries had no policy to
      exempt the poor; in contrast, health workers were exempted in 50 percent of
      countries. Even when an official policy to exempt the poor existed, there were
      numerous informational, administrative, economic, and political constraints to
      effective implementation of these exemptions. The authors argue that user fee
      policy should be developed more cautiously and in a more informed environment.
      Fees are likely to exacerbate existing inequities in health care financing unless
      exemptions policy can effectively reach those unable to pay.

PMID- 9142608
TI  - The class analysis of poverty: is the underclass living off the socially
      available surplus?
AB  - In a recent article Erik Olin Wright argues that the U.S. underclass is a drain
      on the socially available surplus and thus a hindrance to capital accumulation.
      Wright's argument is not supported by available evidence from the United States,
      Canada, and the United Kingdom on the state's distributive activities. This
      evidence suggests that the social welfare necessary to sustain the underclass is
      provided by transfers from wage and salary earners rather than from profit.

PMID- 9142609
TI  - Who pays for the state? A reply to Robert Chernomas and Ardeshir Sepehri.
AB  - Robert Chernomas and Ardeshir Sepehri indicate that various state-supported
      transfers that go to the "underclass" are largely paid for by taxation of
      workers' compensation. Such expenses therefore cannot be considered drains on the
      social surplus which would otherwise be available to dominant classes in the form
      of "exploitation." These arguments are criticized on two grounds. First,
      Chernomas and Sepehri greatly underestimate the total social costs of the
      existence of an underclass, and this broader array of costs almost certainly
      impinges on the social surplus even if direct transfer payments do not. Second,
      they incorrectly identify the empirical target with the relationship of taxation
      to the social surplus. Even if state revenues take the form of an income tax on
      ordinary workers, at least some of this taxation should be considered a deduction
      from social surplus rather than from workers' standard of living (since, in the
      absence of the taxation, workers' equilibrium wages would not increase by the
      equivalent of the taxes).

PMID- 9142610
TI  - Objective measurement of psychiatric symptoms: a quality improvement process for
      inpatient care.
AB  - BACKGROUND: The objective measurement of patient improvement and outcome in
      mental health is a welcome, if challenging, goal. A continuous quality
      improvement (CQI) project was undertaken at an extended care facility in
      northeastern Ohio. The objectives of the CQI project, as delineated in May 1994,
      were to improve the administration of the Brief Psychiatric Rating Scale (BPRS)
      and the presentation and use of findings. EVALUATION STANDARDIZATION: A cross
      functional team, meeting between April and September 1994, made a series of
      recommendations. After a training program was initiated in fall 1994, interrater
      reliability of the BPRS increased. A schedule for BPRS evaluations resulted in
      more even distribution of evaluations within a quarter. DATABASE DEVELOPMENT: A
      new work group, formed in late 1994, reviewed previous system improvements and
      identified future directions. For example, it decided to refine the BPRS
      evaluation form itself to facilitate data entry of the evaluation information and
      to consider possible formats for clinically useful presentation of the serial
      evaluation data. CLINICAL OUTCOME MEASUREMENT: Actual clinical performance
      improvement indicators (as opposed to the administrative compliance indicators)
      were instituted to notify staff of significant patient improvement or
      deterioration, which in turn would prompt refinement of treatment. CURRENT WORK:
      The interrelationships and implications of BPRS-driven clinical outcome(s),
      length of hospital stay, and cost of services are being considered to determine
      the effects of new medications and other treatments. CONCLUDING REMARKS: As the
      complexity and demands of mental health care continue to rapidly evolve, symptom
      measurement and patient outcome are set to become critical determinants in the
      ultimate allocation of increasingly limited resources.

PMID- 9142611
TI  - A peer review feedback method of promoting compliance with preventive care
      guidelines in a resident ambulatory care clinic.
AB  - BACKGROUND: Simple distribution of clinical practice guidelines to physicians
      does not change practice behavior. A low-cost, continuous peer review feedback
      method was used to promote resident physicians' compliance with nine preventive
      care guidelines at the ambulatory care clinic at the Marshall University School
      of Medicine (Huntington, West Virginia). METHODS: Preventive care guidelines were
      distributed and a peer review feedback program was instituted in the resident
      physician primary care practice. The frequency of resident physician use of nine
      preventive care services was assessed and compared during three periods:
      preguideline (September 1, 1993, to March 1, 1994; 148 patients), guideline
      (September 1, 1994, to March 1, 1995; 148 patients), and one-year follow-up
      (September 1, 1995, to March 1, 1996; 150 patients). The patients in the three
      periods were similar in age, gender, and risk for influenza and pneumococcal
      infection. RESULTS: During the guideline period, resident physicians offered
      patients four preventive care services-tetanus toxoid immunization, clinical
      breast examination, Papanicolaou smear testing, and hemoccult testing
      significantly more often than during the preguideline period. All services were
      offered significantly more often during the one-year follow-up period compared
      with the preguideline period and as often as in the guideline period. CONCLUSION:
      A low-cost, continuous peer review feedback program significantly and durably
      improves resident physician compliance with clinical practice guidelines on
      preventive care services. However, the effectiveness of the poor review feedback
      method may not generalize to private practice or other settings. Research on
      other methods to promote compliance with clinical practice guidelines and to
      influence physician behavior in general should continue.

PMID- 9142612
TI  - Reengineering a cardiovascular surgery service.
AB  - BACKGROUND: Reengineering, involving the radical redesign of business processes,
      has been used successfully in a variety of health care settings. In 1994 New York
      University (NYU) Medical Center (MC) launched its first reengineering team, whose
      purpose was to redesign the entire process of caring for patients-from referral
      to discharge-on the cardiovascular (CV) surgery service. REENIGINEERING TEAM: The
      multidisciplinary CV Surgery Reengineering Team was charged with two goals:
      improving customer (patient, family, and referring physician) satisfaction and
      improving profitability. The methodology to be used was based on a reengineering
      philosophy-discarding basic assumptions and designing the patient care process
      from the ground up. THE TRANSFER-IN INITIATIVE: A survey of NYU cardiologists,
      distributed in April 1994, suggested that the organization was considered a
      difficult place to transfer patients. The team's recommendations led to a new,
      streamlined transfer-in policy. The average waiting time from when a referring
      physician requested a patient transfer and the time when an NYUMC physician
      accepted the transfer decreased from an average of 9 hours under the old system
      to immediate acceptance. OTHER INITIATIVES: Three customer satisfaction task
      forces implemented multiple programs to make the service more user friendly. In
      addition, referrals increased and length of stay decreased, without an adverse
      impact on the mortality rate. CONCLUSION: For the first time at NYUMC, a
      multidisciplinary team was given the mandate to achieve major changes in an
      entire patient care process. Similar projects are now underway.

PMID- 9142613
TI  - Accelerating the pace of improvement: an interview with Thomas Nolan. Interview
      by Steven Berman.

PMID- 9142614
TI  - Three-dimensional ultrasound: display modalities in obstetrics.
AB  - Three-dimensional ultrasound (3DUS) has recently been introduced into clinical
      practice. Various techniques are available for display of the volume data. We
      review the importance of selecting the proper display option and rendering mode
      depending on the specific diagnostic question. Current display options include
      (1) arbitrary planar images similar to conventional two-dimensional US images,
      (2) surface rendering with emphasis on soft tissues or skeletal detail, (3)
      stereo viewing using liquid crystal glasses or red/blue glasses, and (4) cine
      review of gated studies. Rotation of volume data also is important in
      understanding/comprehending patient anatomy. The range of rotation angles varies
      depending on the clinical setting. Also data storage requirements increase as the
      number of views increases.

PMID- 9142615
TI  - Prenatal pseudocysts of the germinal matrix in preterm infants.
AB  - Sonographic characteristics of germinal-matrix (PGM) pseudocysts of prenatal
      origin detected on cranial ultrasound in preterm newborns were correlated with
      their outcomes. PGM cysts were classified as typical or atypical, according to
      their location. Typical PGM cysts were present at the head of the caudate nucleus
      or slightly medially, adjacent to the foramen of Monro. Cysts were defined as
      atypical when they were located subependymally elsewhere. Only one infant of 16
      with a typical PGM cyst presented with psychomotor retardation. His cerebral scan
      also showed subependymal calcifications due to cytomegalovirus infection. Three
      babies had cysts in the frontal periventricular zones (atypical PGM cyst). They
      had negative cranial MRI (12-15 months of age) and normal neurological follow-up
      (24 months). In conclusion, isolated prenatal PGM cysts in preterm infants
      correlate with a normal outcome.

PMID- 9142616
TI  - Variations of the middle and inferior right hepatic vein: application in
      hepatectomy.
AB  - We evaluated the anatomic variations of the middle right hepatic vein (MRHV) and
      inferior right hepatic vein (IRHV) and their clinical application to the
      possibility of right subtotal hepatectomy. In 400 of normal livers studied with
      ultrasound, the IRHV was found to drain segment 6 of the liver and flow into the
      inferior vena cava (IVC) in 72 (18%) cases. In 22 (5.5%) cases, the MRHV was
      found to drain segment 5 of the liver and flow into the IVC. The size of the IRHV
      ranged from 0.1 cm to 0.8 cm with an average of 0.46 cm. For the MRHV, the sizes
      ranged from 0.1 cm to 0.9 cm with an average of 0.34 cm. In 10/79 (12.6%) cases
      the IRHV and in 4/ 22 (18.1%) cases the MRHV were bigger than the right hepatic
      vein (RHV). The distance between the RHV and IRHV ranged from 3 cm to 5 cm with
      an average of 3.7 cm. The distance between the RHV and MRHV ranged from 3 cm to
      3.3 cm with an average of 3.1 cm. A hyperechoic edge, similar to that of the
      portal vein, was observed at the wall of the hypertrophic IRHV and was 0.3 cm or
      larger in size. Preoperative delineation of this complex venous anatomy is very
      important. It provides vital information in the preoperative evaluation needed
      before performing a right subtotal hepatectomy with preservation of segment 6 or
      segment 5 of the liver, and with RHV resection. Prior to undertaking a right
      hepatectomy, clamping the hypertrophic MRHV and IRHV electively may minimize
      intra-operative blood loss and extrahepatic spread of the malignancy.

PMID- 9142618
TI  - Applicability of perineal sonography in anatomical evaluation of bladder neck in
      women with and without genuine stress incontinence.
AB  - Thirty-seven patients with proven genuine stress incontinence (GSI) underwent
      ultrasound study to evaluate the bladder neck position relative to the symphysis
      pubis. Sixty-five continent women including 40 parous and 25 nulliparous women
      were recruited as a control group. Several parameters were found to be
      statistically different between incontinent and control groups (P < 0.01). If 28
      degrees or 13 mm were used as the cut-off point for rotational angle (RA) and
      descent of bladder neck (DBN), the sensitivity, specificity, and positive and
      negative predictive values were 78.0%, 76.9%, 64.3%, and 33.3%, respectively. The
      specificity and positive predictive value for GSI increased to 83.1% and 67.6% if
      these two parameters were used together. Perineal sonography is valuable in
      assessing anatomic change of the bladder neck, but it is not a sensitive tool for
      predicting GSI.

PMID- 9142617
TI  - New color Doppler technique for detecting turbulent tumor blood flow: a possible
      aid to hepatocellular carcinoma diagnosis.
AB  - We created a new imaging technique that detects and emphasizes turbulence, which
      is a characteristic of blood flow in hepatocellular carcinoma. We devised two
      indices that determine a characteristic tumor flow, the bi-directional and low
      peak indices. In the phantom study, both indices of turbulence caused by a
      stenosis were much higher. In the clinical study, both indices were significantly
      higher in tumors than in the portal vein or hepatic vein. A turbulent blood flow
      was detected in 77% of tumors, whereas such detection seldom occurred in the
      portal or hepatic vein. This technique has the potential to distinguish
      turbulence in hepatocellular carcinoma.

PMID- 9142619
TI  - Use of ultrasonography in the detection of ureteric reflux in children suspected
      of having urinary infection.
AB  - The present study investigated whether ultrasonography was effective in detecting
      ureteric reflux in children suspected of having urinary infection. Seventeen
      children with febrile episodes and pyuria were enrolled. The ultrasound
      examination revealed ballooning of the renal pelvis during bladder contraction in
      4 children, dilatation of the distal ureters in 6, and small kidney in 2.
      Cystography was performed on the 6 children with these ultrasound abnormalities
      and 1 child with two episodes of suspected urinary infection. Four children
      showed reflux. All of the 4 children had been found to have renal pelvic
      ballooning on ultrasound. None of the 10 children who did not undergo cystography
      had recurrence of urinary infection or significant bacteriuria during a median
      follow-up period of 12 months. Thus, scanning during bladder contraction was
      effective in detecting significant ureteric reflux.

PMID- 9142620
TI  - Color Doppler ultrasound for evaluation of collagen implants after endoscopic
      injection treatment of refluxing ureters in children.
AB  - To determine whether color Doppler ultrasonography (CDUS) would add to the
      understanding of the bladder wall after endoscopic subureteral collagen injection
      (SCIN), 25 patients were studied with CDUS. The kidney length and echogenicity,
      the volume of the collagen, the mean length of the urinary jet, the longitudinal
      and transverse angles, and the distance between the origin of the jet and the
      midline of the bladder were measured 1 day, 1 month, and 3 months after SCIN and
      compared to the results of micturating cystourethrograms (MCUs) performed 3
      months after SCIN. The collagen was hyperechogenic compared to the bladder wall
      at the time of injection, and was isoechogenic 1 and 3 months after SCIN. CDUS
      showed the relationship between the injected collagen and the position of the
      ureteral orifice. The measurements of jet length, angle, and distance of the
      ureteral orifice from the midline did not correlate with vesicoureteral reflux
      assessed by MCU. Although CDUS may demonstrate the location, the size of the
      injected collagen implant, and its relationship to the ureteral orifice, it is as
      yet unable to predict vesicoureteral reflux after SCIN.

PMID- 9142621
TI  - Diffuse xanthogranulomatous pyelonephritis in childhood.

PMID- 9142622
TI  - Testicular ultrasound in Carney complex: report of three cases.

PMID- 9142623
TI  - Nonpalpable lymph nodes of the neck: assessment with US and US-guided fine-needle
      aspiration biopsy.
AB  - Ultrasound (US) and US-guided fine-needle aspiration biopsy (FNA) were performed
      in 91 nonpalpable neck nodes of 70 patients, 98% of which had known malignancy.
      Various sonographic findings were evaluated for predicting malignancy. The
      accuracy of US-guided FNA for detecting malignancy was 88%, with 96% sensitivity
      and 94% specificity. The ratio of minimal to maximal axial diameters of a node
      was most valid for predicting malignancy with US. A ratio of more than 0.55
      yielded the highest accuracy (80%) (92% sensitivity, 63% specificity). Addition
      of any other factors to this criterion did not improve its accuracy. US and US
      guided FNA are accurate for the assessment of nonpalpable neck nodes. Lymph nodes
      with a round configuration should be biopsied in patients with known malignancy.

PMID- 9142624
TI  - Transperineal versus transvaginal color Doppler imaging of the uterine
      circulation.
AB  - Transperineal sonography has been described as being useful in assessing patients
      in special clinical situations such as posterior placenta previa, preterm labor,
      stress incontinence, and vaginal atresia. We explored the feasibility of this
      approach in assessing the uterine circulation in 54 subjects, of whom 36 were
      postmenopausal. We found that visualization of the uterine artery by the
      transperineal approach was satisfactory in most patients. The uterine arterial
      Doppler indices obtained from this approach were compared with those obtained by
      the transvaginal route. Highly significant correlations were found (correlation
      coefficient tau for pulsatility index = 0.74, p < 0.0001). No significant
      differences in results between the two approaches were detected using the
      Wilcoxon Matched-Pairs Signed-Rank test. We conclude that transperineal Doppler
      studies of the uterine circulation are possible and may be useful in certain
      patient groups.

PMID- 9142625
TI  - Appearance of the uterus by ultrasound immediately after placental delivery with
      pathologic correlation.
AB  - The purpose of this study was to compare the ultrasound appearance of the uterus
      immediately after the placenta was delivered with the gross and histologic
      findings obtained by manual exploration and sponge curettage. One hundred thirty
      one patients underwent a sonographic assessment of the uterus within 5 minutes of
      placental delivery. A manual exploration and sponge curettage were performed with
      2 minutes of the ultrasound examination, and the specimens were assessed for
      gross and histologic evidence of retained products of conception. Twenty-four
      (18.8%) of the patients had documented evidence of retained products of
      conception either by gross inspection or histologic assessment. Nineteen (15%) of
      the patients had what appeared to be retained products on ultrasound examination.
      Using our sonographic description of retained products of conception, the
      sensitivity, specificity, positive predictive value, and negative predictive
      value of ultrasound in detecting retained products was 44%, 92%, 58%, and 87%,
      respectively. The ultrasound findings in patients with retained products of
      conception were: a normal endometrial cavity in 9 (37.5%), echogenic mass in 6
      (25%), heterogenous mixed density mass in 5 (21%), and fluid only in 4 (16.6%).
      Of the 6 cases with an echogenic mass, all were associated with retained products
      of conception. The ultrasound appearance of retained products of conception in
      the immediate time period after placental delivery is highly variable.

PMID- 9142626
TI  - Preoperative evaluation of cystic teratoma: what does color Doppler add?
AB  - The aim of this prospective study lasting 4 years was to develop a scoring system
      using clinical parameters, sonographic findings, and transvaginal color and
      pulsed Doppler impedance values for the preoperative recognition of cystic
      teratoma. A total of 887 benign and malignant adnexal masses, among which 102
      were histologically proved to be cystic teratomas, were evaluated. Using
      morphological criteria, cystic teratoma was successfully predicted in 95
      patients. The sensitivity and specificity of a morphological scoring system were
      93.1% and 99.4%, respectively, while positive and negative predictive values were
      95.0% and 99.1%. A scoring system using both morphology and vascular assessment
      demonstrated higher sensitivity and specificity (99.02%, 99.75%). The application
      of a scoring system combining morphology and vascularity improves the accuracy of
      diagnosing cystic teratoma and of separating this entity preoperatively from
      other benign and malignant ovarian conditions.

PMID- 9142627
TI  - Assessment of right hepatic artery involvement in patients with biliary tract
      cancer using color Doppler ultrasonography.
AB  - The accuracy of color Doppler ultrasonography (CDUS) in diagnosing right hepatic
      artery (RHA) involvement was preoperatively evaluated in 28 patients with biliary
      tract cancer. When a tumor partially or completely surrounded the RHA, the
      circumferential involvement was diagnosed as positive. With B-mode
      ultrasonography imaging alone in the 10 nonsurgical patients, the correspondence
      rates with angiography for the presence of invasion, absence of invasion, and
      overall were 33%, 0%, and 10%, respectively. However, CDUS allowed clearer
      visualization of the RHA than did B-mode imaging, and the correspondence rates of
      CDUS with angiography were 100%, 43%, and 60%, respectively. In the 13 surgical
      patients, the accuracy levels of B-mode imaging, CDUS, computed tomography, and
      angiography for the detection of RHA involvement were 46%, 77%, 58%, and 92%,
      respectively, when compared with surgical and histopathologic findings. Although
      the accuracy of CDUS was lower than that of angiography, it can be performed
      repeatedly and noninvasively. CDUS is expected to be useful for the initial
      assessment of RHA involvement.

PMID- 9142628
TI  - Color Doppler ultrasonographic findings in intratesticular varicocele.

PMID- 9142629
TI  - Prenatal ultrasonographic findings of intra-abdominal cystic lymphangioma: a case
      report.

PMID- 9142630
TI  - Endoscopic ultrasonographic diagnosis of gastric lymphangioma.

PMID- 9142631
TI  - Prenatal diagnosis of fetal bifid great toe.

PMID- 9142632
TI  - Condyloma acuminatum of the bladder in a patient with AIDS: radiological
      findings.

PMID- 9142633
TI  - Clinical update: management of acute pancreatitis.
AB  - The management of acute pancreatitis commences with confirming the diagnosis and
      establishing the aetiology. Improved methods of assessing the biliary tree may
      reduce the number of patients regarded as having idiopathic pancreatitis.
      Detailed clinical and laboratory protocols, designed to assess severity, have no
      major advantage over clinical assessment. The contrast-enhanced computed
      tomography scan is important to assess the degree of pancreatic necrosis and to
      detect local complications. The treatment of pancreatitis continues to be largely
      supportive. However, controlled studies support the use of antibiotics in severe
      acute pancreatitis and indicate a possible role for the use of octreotide and
      antioxidants. The place of endoscopic and surgical intervention is becoming
      better defined. Once an attack has passed, further investigation is often
      required in a bid to prevent further episodes of inflammation.

PMID- 9142634
TI  - Colonic retinoblastoma protein and proliferation in cancer and non-cancer
      patients.
AB  - Both suppressor oncogene and proliferative activity are believed to indicate
      colon cancer risk. The retinoblastoma (Rb) gene is a suppressor oncogene
      affecting cell differentiation. Retinoblastoma gene inactivation is associated
      with tumour development. However, the relation of the Rb protein to cell
      proliferation and colon tumour formation is unknown. Retinoblastoma protein
      quantity was correlated with proliferative activity in flat, unaffected mucosa
      specimens from 36 cancer patients, 21 non-cancer control subjects and in 29
      tumour tissue samples from cancer patients. Nuclear Rb protein was measured by
      using automated CAS-200 image analysis of monoclonal antibody labelled frozen
      sections from fresh, surgically removed tissue. All colon cells within 15 whole
      crypts were imaged. Proliferative activity was also measured by using analysis
      with Ki-67 monoclonal antibody. Retinoblastoma protein content correlated
      directly with proliferative activity in flat mucosa of non-cancer control
      subjects (r = 0.63; P < 0.001; n = 21). A significant correlation was also found
      in flat mucosa specimens of non-metastatic (Duke's stages A and B) cancer
      patients (r = 0.52; P < 0.01; n = 22). However, Rb protein did not correlate with
      proliferation in flat mucosa from metastatic (Duke's stages C and D) cancer
      patients (r = 0.03; NS; n = 14) or in cancer tissue (r = 0.068; NS; n = 29).
      Mucosal Rb protein in the colon normally increases as proliferation increases.
      Dissociation between Rb protein and colon proliferation may occur in flat mucosa
      in patients with a higher risk of metastatic tumour growth. Future studies
      comparing Rb protein quantity and proliferative activity may help identify high
      risk colon cancer patients.

PMID- 9142635
TI  - Case report: eosinophilic colitis with high antibody titre against Ascaris suum.
AB  - Eosinophilic gastroenteritis (EGE) is an inflammatory disease characterized by
      eosinophilic infiltration of the gastrointestinal tract accompanied by varying
      abdominal symptoms and usually by peripheral blood eosinophilia. Although the
      precise aetiology of EGE remains to be determined, contribution of allergic
      process to certain allergens, such as foods, drugs and parasites, has been
      repeatedly proposed as the pathogenesis of the disease. Here we report on a rare
      case of a woman who had extensive eosinophilic infiltration in the descending and
      rectal colon with a high titre of IgG antibody against Ascaris suum. The patient
      was successfully treated with prednisolone.

PMID- 9142636
TI  - Case report: endoscopic ultrasonographic findings of mucosal prolapse syndrome.
AB  - A 41-year-old man with mucosal prolapse syndrome received endoscopic
      ultrasonography. The lesion was mildly hypoechoic and irregular, with extension
      into the muscularis propria and disappearance of the normal mucosal and
      submucosal layers. In addition, an enlargement of the muscularis propria,
      bridging towards the mucosal layer with merging of the two layers, was observed.
      These findings suggest the usefulness of endoscopic ultrasonography in the
      diagnosis of mucosal prolapse syndrome.

PMID- 9142637
TI  - Review: intrahepatic cholestasis. A puzzling disorder of pregnancy.
AB  - Intrahepatic cholestasis of pregnancy is characterized by skin pruritus and a
      biochemical cholestasis of mild to moderate severity appearing during pregnancy
      (mainly in the third trimester) and disappearing after delivery. It recurs in 40
      60% of future pregnancies. The intensity of pruritus and the laboratory
      alterations (increased serum bile salts and transaminases in almost all patients,
      hyperbilirubinaemia in 20% of patients) fluctuate during one pregnancy and also
      vary in subsequent affected pregnancies. This disease has no meaningful
      consequences for the mother; in contrast, it is associated with an increased risk
      of foetal distress, causing premature deliveries and stillbirths. Cholestasis of
      pregnancy has been recognized in most countries and ethnic groups but its
      prevalence is higher in Chile (14% of deliveries in 1975 and approximately 4% in
      1995) and in Sweden than in other countries. The cause in unknown. Sex hormones,
      mainly oestrogens and progesterone, appear to be involved in its pathogenesis. An
      interplay between a genetic metabolic predisposition and some environmental
      factor(s) is apparently relevant. Clinical and experimental studies suggest that
      a marginal selenium deficiency could be a dietary pathogenic factor. Some drugs
      attenuate pruritus and improve maternal cholestasis, but not the foetal
      prognosis. Ursodeoxycholic acid (UDCA) administration provides a significant
      improvement in maternal pruritus and in the biochemical abnormalities, with no
      adverse effects in the mother or child. Recent clinical and experimental studies
      show that UDCA administration improves maternal disease and foetal prognosis
      without any detectable adverse effects.

PMID- 9142638
TI  - Review: hepatitis B and liver transplantation.
AB  - Liver transplantation in hepatitis B virus (HBV)-infected patients is very
      commonly followed by recurrence of infection in the transplanted liver. Most
      recipients with HBV recurrence will develop chronic hepatitis that follows a more
      aggressive course than is seen in non-immuno-compromized subjects and this
      frequently results in graft failure. The presence of hepatitis B e antigen or
      significant levels of HBV-DNA in the serum is highly predictive of recurrence and
      this has led to the view that patients, whose serum is positive for these
      conventional markers of replication, should be excluded from transplantation. The
      key to improving the results of transplantation in patients with HBV infection
      lies in the development of effective strategies to prevent reinfection. High dose
      anti-HBs immunoglobulin is effective in patients who are coinfected with
      hepatitis D, those transplanted for fulminant hepatitis and cirrhotic patients
      who have very low levels of viral replication prior to transplantation.
      Unfortunately, immunoprophylaxis does not seem to influence the outcome in those
      patients with higher levels of replication. There are several new orally active
      nucleoside analogues that and potent inhibitors of hepatitis B replication that
      may be effective for both the prevention and treatment of recurrent disease. The
      most promising are lamivudine (2',3',dideoxy,3',thiacytidine) and famciclovir (a
      guanosine analogue). Both agents have been extensively evaluated in animal models
      of HBV and have been shown to rapidly suppress viral replication. The initial
      experience with these agents in liver transplant recipients has been promising
      and a number of studies are currently underway to determine whether these drugs,
      used alone or in combination with immunoprophylaxis, are able to prevent
      recurrence in those patients at highest risk of post-transplant HBV recurrence.

PMID- 9142639
TI  - Immunohistochemical evidence of insulin-like growth factor II in human small
      hepatocellular carcinoma with hepatitis C virus infection: relationship to fatty
      change in carcinoma cells.
AB  - It has recently been reported that insulin-like growth factor II (IGF-II) may
      play a role in the pathogenesis of hepatocellular carcinoma (HCC). We studied the
      relationship between the expression of IGF-II and fatty change in human small HCC
      using immunohistochemical staining techniques. Liver biopsy specimens were
      obtained from 35 patients with HCC (consisting of 15 patients with fatty change
      and 20 patients without fatty change). All patients had serum markers for the
      hepatitis C virus (HCV) and histological findings obtained from non-tumourous
      lesions showed liver cirrhosis or chronic active hepatitis. Immunohistochemical
      staining was performed using a monoclonal antibody against rat IGF-II. A positive
      immunoreaction was found in 69% (24/35) of HCC. Insulin-like growth factor II was
      immunodetected in 80% (12/15) of HCC with fatty change but only in 60% (12/20) of
      those without fatty change. In most cases, IGF-II was not found in hepatocytes
      from non-tumourous lesions. We believe this to be the first time that IGF-II has
      been detected immunohistochemically in small HCC derived from HCV infection. This
      growth factor was more frequently immunodetected in HCC with fatty change than
      without. As insulin is an essential factor for the metabolism of fatty acids, IGF
      II may play an important role in both fatty degeneration and in the proliferation
      of HCC cells. Furthermore, immunohistochemical IGF-II staining may contribute to
      the diagnosis of HCC, particularly in early stages accompanied by fatty change.

PMID- 9142640
TI  - Case report: primary cystic keratinizing squamous cell carcinoma of the liver in
      a patient with treated nasopharyngeal carcinoma.
AB  - Primary squamous cell carcinoma of the liver is very rare; only 18 cases have
      been recorded. In the present report we document an additional case who had a
      unique history of stage III non-keratinizing nasopharyngeal carcinoma treated
      with a full course of radiotherapy in July 1993. Two small hypoechoic cyst-like
      lesions in the left hepatic lobe were identified at the same time. In July 1995
      the 50-year-old patient reported to be suffering from abdominal fullness and
      tenderness. A large hypodense tumour was demonstrated in the left hepatic lobe by
      abdominal echography. The patient was diagnosed as having metastatic carcinoma
      and received two courses of pre-operative chemotherapy followed by left lobectomy
      of the liver and resection of adherent tissues on 9 August 1995. Pathological
      study demonstrated a larger hepatic cystic keratinizing squamous cell carcinoma,
      which most likely arose from a solitary hepatic cyst. Tumour seedings, probably
      secondary to tumour rupture, were also revealed on the omentum, peritoneum and
      diaphragm. However, regional lymph nodes were fee of tumour. Systemic work-up
      failed to demonstrate evidence of local recurrence of nasopharyngeal carcinoma,
      metastatic lesion or any second primary tumour site.

PMID- 9142641
TI  - Plasma concentrations of cyclic 3', 5'-guanosine monophosphate in patients with
      cirrhosis: relationship with atrial natriuretic peptide and haemodynamics.
AB  - Little is known about the plasma concentrations of cyclic 3',5'-guanosine
      monophosphate (cGMP) in patients with cirrhosis. However, plasma cGMP
      concentrations provide information on cellular cGMP production by particulate
      guanylyl cyclases (which are stimulated by natriuretic peptides, such as atrial
      natriuretic peptide; ANP). In contrast, because intracellular cGMP elicits
      vasorelaxant mechanisms, plasma cGMP concentrations may be related to
      haemodynamic alterations in patients with cirrhosis. The aim of the present study
      was to measure plasma cGMP concentrations in patients with cirrhosis and controls
      and to examine the relationship between cGMP levels and plasma ANP concentrations
      and haemodynamic values. Plasma concentrations of cGMP and ANP and splanchnic and
      systemic haemodynamics were measured in 23 subjects; 13 subjects had cirrhosis
      and 10 were controls. All subjects had normal glomerular filtration. Plasma cGMP
      concentrations were significantly higher in patients (6.5 +/- 0.8 pmol/mL) than
      in controls (2.7 +/- 0.4 pmol/mL), while plasma ANP concentrations did not
      significantly differ between the two groups (127 +/- 22 and 123 +/- 27 pg/mL,
      respectively). In patients with cirrhosis, no significant correlation was found
      between plasma cGMP concentrations and plasma ANP concentrations, hepatic venous
      pressure gradient, cardiac output or systemic vascular resistance. In conclusion,
      in patients with cirrhosis, increased plasma cGMP concentrations may be due to an
      activation of particulate guanylyl cyclases by natriuretic peptides other than
      ANP. The present study suggest that plasma cGMP concentrations are not related to
      cirrhosis-induced haemodynamic alterations.

PMID- 9142642
TI  - Case report: primary hepatic lymphoma associated with chronic liver disease.
AB  - We report on a case of primary hepatic lymphoma that developed in a patient with
      chronic hepatitis C. Given that Japan is an area endemic for both hepatitis B and
      C viruses, we reviewed 51 Japanese cases of primary hepatic lymphoma, addressing
      the question as to whether the Japanese cases have unique characteristics and
      whether there is a causal relationship to the presence of chronic liver disease.
      Primary hepatic lymphoma most commonly affected middle-aged males. Presenting
      symptoms and physical findings were non-specific. Aminotransferases tended to
      stay in the low range compared with marked increases in lactate dehydrogenase.
      Sixteen patients (31%) had chronic liver disease, eight had liver cirrhosis and
      eight had chronic hepatitis, suggesting that there is a possible aetiological
      link between chronic liver disease and primary hepatic lymphoma.

PMID- 9142643
TI  - Effects of glycyrrhizin on immune-mediated cytotoxicity.
AB  - Intravenous administration of glycyrrhizin is known to decrease elevated plasma
      transaminase levels in patients with chronic viral hepatitis, in which immune
      mediated cytotoxicity by cytotoxic T lymphocytes and tumour necrosis factor (TNF)
      alpha is considered to play an important pathogenic role. However, the
      immunological interpretation of the transaminase-lowering action of glycyrrhizin
      is not known. Studies were performed to elucidate this action immunologically by
      assessing the effects of glycyrrhizin on immune-mediated cytotoxicity using an
      antigen-specific murine CD4+ T hybridoma line, which exhibits cytotoxicity
      against antigen-presenting cells after stimulation with specific antigen, and a
      murine TNF-alpha-sensitive fibroblast line. Glycyrrhizin inhibited the cytotoxic
      activity of the T cells against antigen-presenting cells and also suppressed TNF
      alpha-induced cytotoxicity in the TNF-alpha-sensitive cell line in vitro. These
      results suggest that the decrease of elevated transaminase levels by glycyrrhizin
      in patients with chronic viral hepatitis is mediated in part by inhibition of
      immune-mediated cytotoxicity against hepatocytes.

PMID- 9142644
TI  - Relationship between cellular ATP content and cellular functions of primary
      cultured rat hepatocytes in hypoxia.
AB  - The importance of oxygen in maintaining the functional integrity of hepatocytes
      has been well established in a variety of experimental models, such as in vivo,
      perfused liver and isolated hepatocytes. However, one of the shortcomings of
      these systems is their short life span. Therefore, we have examined the effects
      of long-term hypoxia on cellular adenine nucleotide content and cellular
      functions, such as albumin production, urea production and DNA synthesis, in
      adult rat hepatocytes in primary culture. Hepatocytes were cultured at a density
      of 11 x 10(4) and 5 x 10(4) cells/0.18 mL per cm2 for the study of albumin and
      urea production and DNA synthesis, respectively, at various oxygen tensions (20,
      12, 8 and 5%) for 24 h. Cellular ATP content in cultured hepatocytes in hypoxia
      gradually declined, corresponding to the decrease in oxygen tension, and the
      cellular ATP level at 5% oxygen was approximately 20% of that at 20% oxygen.
      Albumin production also decreased in parallel with the decrease in cellular ATP
      content in cultured hepatocytes in hypoxia. However, even when cellular ATP
      content gradually declined corresponding with the decrease in oxygen tension in
      cultured hepatocytes in hypoxia, such as at 8 or 5% oxygen, urea production
      remained at a high level; in contrast, DNA synthesis was completely suppressed.
      These results suggest that the cellular ATP content decreases in cultured
      hepatocytes during long-term hypoxia in relation to oxygen tension and that the
      relationship between decreased ATP levels and liver function in cultured
      hepatocytes during hypoxia differs for albumin production, urea production and
      DNA synthesis.

PMID- 9142645
TI  - Nitric oxide synthase in neurons of the human gall-bladder and its colocalization
      with neuropeptides.
AB  - The distributions of nerve cells and fibres that are immunoreactive for nitric
      oxide synthase (NOS) have been investigated in the human gall-bladder. In
      addition, the colocalization of NOS immunoreactivity (IR) with neuropeptide Y
      (NPY), pituitary adenylyl cyclase activating peptide (PACAP), somatostatin (SOM),
      substance P (SP), tyrosine hydroxylase (TH) and vasoactive intestinal peptide
      (VIP)-IR was determined. Nitric oxide synthase-IR nerve cell bodies comprised 13
      and 30% of nerve cells in ganglia of the fibromuscular and subepithelial layers,
      respectively. To determine these percentages, neuron-specific enolase-IR was used
      as a marker for all nerve cells. Although SOM- and VIP-IR nerve cell bodies were
      found in both ganglia, they rarely contained NOS-IR. In the fibromuscular layer,
      NOS-IR nerve fibres were abundant and most PACAP-, SOM- and VIP-IR fibres and
      many NPY-IR fibres were also NOS positive. No colocalization was observed between
      NOS- and SP- or TH-IR. In the mucosal layer, moderate numbers of NOS-IR fibres
      were found and the degree of colocalization of NOS-IR with each of NPY-, PACAP-,
      SOM-, SP- and VIP-IR were as follows: PACAP and NPY > VIP > SOM and SP. Nitric
      oxide synthase and TH were not colocalized in mucosal fibres. These results
      suggest that nerve fibres in the fibromuscular layer in the human gall-bladder
      with the chemical coding NOS/NPY/PACAP/SOM/VIP are axons of inhibitory motor
      neurons. Nitric oxide synthase-IR fibres in the mucosal layer that contained NPY,
      PACAP, SOM, SP and VIP with various degrees of colocalization probably contribute
      to the control of epithelial secretion or absorption.

PMID- 9142646
TI  - Reflections on the years in interferon research.
AB  - This review presents a personal overview of my interferon research. I relate the
      interests of my laboratory to the overall progress in the interferon field during
      the past 25 years. On behalf of the interferon community, I thank the Milstein
      family for their generosity and wisdom to recognize and honor basic research. The
      role of basic research has been downplayed periodically, but I hope it will
      become obvious from my recollections that it has been basic research that has
      made the field as exciting as it is today and that that basic research provided a
      rational basis for new types of approaches for the clinical use of interferon and
      other cytokines. My recollections also reveal that research, especially as
      practiced today, reflects a team effort, even when a honor like the Milstein
      Award is made to an individual, and that interactions among the members of a
      research group, as well as their colleagues in the field, stand as one of the
      most enjoyable features in the life of a scientist.

PMID- 9142648
TI  - Early induction of proinflammatory cytokine and type I interferon mRNAs following
      Newcastle disease virus, poly [rI:rC], or low-dose LPS challenge of the mouse.
AB  - Numerous cytokines induce symptoms characteristic of the flu syndrome common to
      acute viral infections. To better characterize the cytokine mRNA profile
      associated with the early phase of this syndrome, we examined the induction of
      cytokine mRNAs in spleens of mice 1, 2, and 4 h following intraperitoneal
      inoculation of Newcastle disease virus (NDV). The reverse transcriptase
      polymerase chain reaction was used to detect mRNAs for mouse proinflammatory
      cytokines [interleukin (IL)-1 alpha, IL-1 beta, IL-6, tumor necrosis factor-alpha
      (TNF-alpha), macrophage colony-stimulating factor (M-CSF), and interferon (IFN)
      gamma] and type I IFNs (IFN-alpha 4 and IFN-beta). We observed a rapid (within 2
      h) induction of most of these cytokine mRNAs in the mouse spleen following
      challenge with live NDV or the viral stimulant poly[rI:rC]. IL-1 beta, M-CSF, and
      IFN-gamma mRNAs were also induced by heat-inactivated NDV, suggesting the
      possibility of endotoxin contamination of the virus (confirmed by Limulus lysate
      assay). Examination of cytokine induction by comparable doses of
      lipopolysaccharide indicated that endotoxin contamination could account for the
      cytokine mRNA-inducing activity of the heat-inactivated virus. These studies
      point to a critical control (heat-inactivated virus) for viral cytokine studies.
      In addition, they indicate that certain cytokine mRNAs (IL-1 alpha, IL-6, M-CSF,
      IFN-gamma, IFN-alpha, and IFN-beta) are rapidly induced in the spleen when live
      virus is inoculated intraperitoneally, independently of contaminating endotoxin.

PMID- 9142647
TI  - Tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta 1
      (TGF-beta 1) inhibit the expression and activity of Na+/K(+)-ATPase in FRTL-5 rat
      thyroid cells.
AB  - We recently reported that tumor necrosis factor-alpha (TNF-alpha) induction of
      the synthesis and secretion of transforming growth factor (TGF)-beta 1 by FRTL-5
      cells is a thyroid-stimulating hormone (TSH)-dependent and age-dependent process.
      TNF-alpha is only cytotoxic to aged (> 40 passages) FRTL-5 cells grown in TSH
      containing medium, whereas TGF-beta induces programmed cell death (apoptosis) in
      epithelial cells but not in FRTL-5 cells, which otherwise retain many properties
      of normal thyroid follicular cells. This cell line is, therefore, a convenient
      model for studies on the TSH-dependent and age-dependent inhibitory effects of
      these cytokines on epithelial cell growth, viability, and function. One prominent
      effect of TNF-alpha (and TGF-beta 1) on FRTL-5 cell function is suppression of
      iodide uptake, which is markedly stimulated by TSH. In aged FRTL-5 cells, iodide
      uptake is only about 10% that of young control cells. Na+/K(+)-ATPase activity,
      which drives iodide uptake by thyroid cells, is inhibited by TNF-alpha and TGF
      beta. The following experiments quantitate the effects of TSH, aging, TNF-alpha,
      and TGF-beta 1 on the expression and activity of Na+/K(+)-ATPase activity in FRTL
      5 cells. Young (< 20 passages) and aged (> 40 passages) FRTL-5 cells were treated
      with various doses (0-100 ng/ml) of recombinant human TNF-alpha or TGF-beta 1 for
      various times (0-3 days) with and without 2 U/liter TSH. These treatments reduced
      the rate-limiting Na+/K(+)-ATPase beta 1 mRNA level and Na+/K(+)-ATPase activity
      in parallel in a dose-dependent and time-dependent fashion. Aged FRTL-5 cells
      were more sensitive to the inhibitory effects of TNF-alpha, whereas young cells
      were more sensitive to the suppressive effects of TGF-beta 1 on the expression
      and activity of Na+/K(+)-ATPase. We conclude that inhibition of Na+/K(+)-ATPase
      activity by TNF-alpha and TGF-beta in FRTL-5 cells is differentially affected by
      aging and that this inhibitory effect can be dissociated from effects on cell
      viability.

PMID- 9142649
TI  - 4-Hydroxynonenal inhibits interleukin-1 beta converting enzyme.
AB  - Lipid peroxidation results from the interaction of reactive oxygen species and
      polyunsaturated fatty acids. Metabolites generated from oxidative stress play an
      important role in the pathogenesis of a variety of diseases and biologic
      processes. One such product generated from lipid peroxidation in 4-hydroxynonenal
      (HNE). HNE is thiol reactive and exhibits numerous cellular effects. In this
      study, the inhibition of the cysteine protease, interleukin-1 beta (IL-1 beta)
      converting enzyme (ICE), by HNE in human blood mononuclear cells was
      investigated. HNE blocked the release of lipopolysaccharide (LPS)-stimulated IL-1
      beta (EC50 5 microM) and IL-10 (EC50 2 microM) in a dose-dependent manner and, to
      a lesser extent, tumor necrosis factor-alpha (TNF-alpha) (EC50 15 microM)
      release. However, LPS-stimulated elevation of intracellular proIL-1 beta levels
      was not affected by HNE treatment. HNE inhibited ICE activity in lysed cells in a
      similar dose-dependent manner, measured by hydrolysis of the fluorogenic
      substrate YVAD-AMC and recombinant proIL-1 beta. To confirm that the inhibition
      of ICE activity by HNE was not an indirect effect, ICE activity was examined
      using purified recombinant human ICE (rHu-ICE). HNE inhibited rHu-ICE activity in
      a dose-dependent manner. Thus, low levels of HNE can suppress mononuclear cell
      release of IL-1 beta, probably by interacting with the active site cysteine of
      ICE. These results have implications for modulating mononuclear cell function
      during oxidative stress conditions.

PMID- 9142650
TI  - Relationship among circulating interferon, tumor necrosis factor-alpha, and
      interleukin-6 and serologic reaction against parasitic antigen in human
      hydatidosis.
AB  - Human hydatidosis is a parasitic disease vectored by the larval stage cestode
      Echinoccocus granulosus. It constitutes a major health problem in North Africa.
      We investigated the production of circulating interferon (IFN), tumor necrosis
      factor-alpha (TNF-alpha), and interleukin-6 (IL-6) in Algerian patients with
      liver, lung, or ocular hydatidosis. In all, 101 serum samples from these patients
      with analyzed. Immunoreactivity and cytokine activities were undetectable in sera
      from ocular hydatidosis patients. However, we observed the presence of IFN (a
      mixture of IFN-alpha, IFN-beta, and IFN-gamma, range 32-500 U/ml), TNF-alpha
      (range 32-100 U/ml), and IL-6 (range 32-500 U/ml) in all patients who had liver
      or lung cysts or both and displayed immunoreactivity against parasitic antigen
      (antigen 5). After surgical removal of the cysts, serum cytokine levels declined
      rapidly and were undetectable at 30 days. IFN and IL-6 activity was undetectable
      in sera from two liver hydatidosis patients who relapsed and did not display any
      immune response against parasitic antigen. These results suggest that in liver
      and lung hydatidosis, cytokine production contributes to the host defense
      mechanism against the extracellular parasite.

PMID- 9142651
TI  - Cloning of chicken interferon regulatory factor-2 (IRF-2) cDNA: expression and
      mapping of the IRF-2 gene.
AB  - A cDNA clone encoding a member of the avian interferon regulatory factor (IRF)
      family homologous to mammalian IRF-2 was isolated from cDNA library from
      poly[rI:rC]-induced chicken embryo fibroblasts (CEF). The deduced amino acid
      sequence shows a characteristic DNA binding domain of 124 amino acids at the
      amino-terminal end with 96.8% identity to human and 96% to mouse IRF-2.
      Identities in the C-terminal part are 77.5% and 77%, respectively. Identity to
      all other known members of the chicken IRF (Ch-IRF) family is distinctly lower.
      In C32 cells, an IRF-2 mRNA of 2.4 kb is constitutively expressed in very low
      amounts but is inducible by Ch-IFN in the absence or presence of cycloheximide.
      The Ch-IRF-2 gene is a single copy gene and was mapped by fluorescence in situ
      hybridization to the long arm of chromosome 4.

PMID- 9142653
TI  - Prion; the unconventional slow infectious agent.

PMID- 9142652
TI  - One-way synergistic effect of low superantigen concentrations on
      lipopolysaccharide-induced cytokine production.
AB  - Lipopolysaccharides (LPS) of gram-negative bacteria and superantigens of gram
      positive bacteria are among the main causes of sepsis and septic shock. Symptoms
      are initiated primarily by the release of endogenous mediators, especially
      cytokines. In the last few years, increasing evidence for the clinical relevance
      of mixed sepsis caused by coinfections with both types of bacteria has been
      found. Therefore, we developed an in vitro mixed sepsis model investigating the
      effect of different superantigen doses, in combination with different LPS
      concentrations, on cytokine production in human PBMCs using ELISA and RT-PCR.
      Low, in vivo relevant concentrations of the superantigen toxic shock syndrome
      toxin-1 (TSST-1) synergistically enhance LPS-induced production of interferon
      gamma (IFN-gamma) interleukin-1 beta (IL-1 beta), IL-6, and IL-10, but low LPS
      has no comparable effect. Signal transduction studies with different inhibitors
      suggest that this one-way synergism is caused by an interaction between the cAMP
      and the PIP2 signaling pathway. Furthermore, our findings support the idea that
      this interaction is one important crossover point of signal transduction pathways
      by LPS and superantigens, which seems to be predominantly regulated by IFN-gamma
      and PGE-2. The identification of additional crossover points in the genesis of a
      mixed sepsis and their selective influence could lead to identical treatment of
      both gram-negative and gram-positive sepsis.

PMID- 9142654
TI  - Standard bone-age of infants and children in Korea.
AB  - To evaluate the developmental status of children and adolescents, a bone-age
      chart based on the radiograph of hand and wrist has been used in many countries.
      Bone-age reflects not only the functional status of various hormones but also the
      influence of chronic disease and it has been used more widely than other indices
      such as the height-weight-age table. As a standard bone-age chart has not been
      established in Korea, a foreign bone-age chart has been used in clinics. To make
      a Korean standard bone-age chart, we took the radiographs of the left hand of
      about 5,400 children covering the whole country, and 3,407 radiographs of 1,830
      boys and 1,577 girls ranging from two months to 16 years of age were selected and
      analyzed for bone maturity scores by the TW2-20 method. The range of ages were
      divided into 27 groups, and the radiographs of 50th percentile score were chosen
      as the standard bone-ages for the median age of each group. The youngest and
      oldest chronological age which had the same TW2-20 score of the standard bone-age
      were decided as the range of variation from the median age. We hope that a Korean
      standard bone-age chart can be used as the radiological index in the evaluation
      of the developmental status in Korean children and adolescents.

PMID- 9142655
TI  - National cholesterol treatment guidelines in Korean population--setting-up the
      cutpoints for high blood cholesterol.
AB  - National Cholesterol Treatment Guidelines are different according to race and
      country, and change year by year, because the distribution of lipid and
      lipoprotein levels are different by genetic background, dietary habit and life
      style. So it is mandatory to set-up the national cholesterol treatment guidelines
      based on the epidemiologic results. To establish the cutpoints for
      hypercholesterolemia specific to the Korean population, we selected the
      laboratories, whose inaccuracies of cholesterol measurement were less than 5%, in
      the external laboratory quality assessment survey, and performed epidemiological
      survey on the distribution of cholesterol levels, and other risk factors of
      coronary heart disease (CHD). As a result, prevalence of CHD risk factors was
      very high in hypertension (28.0%) and relatively low in diabetes (2.8%). Smokers
      were 42.6% of total subjects. Thirteen percent of subjects had a family member(s)
      who was suffering from or had of hypertension, stroke, and heart diseases. The
      average cholesterol level of a Korean was 187 mg/dL, which was about 25 mg/dL
      lower than that of United States. The 75th percentile to total cholesterol was
      210 mg/dL and 90th percentile 235 mg/dL. The cutpoint for borderline-high
      cholesterol levels provide a major guideline for initiation of dietary and
      exercise therapy. We propose the cutpoint for borderline-high cholesterol levels
      as 200 instead of 210 mg/dL to initiate more active dietary and exercise therapy,
      and we also propose the temporary cutpoint for high blood cholesterol levels as
      240 mg/dL instead of 235 mg/dL, which is a reasonable cutpoint considering
      medical insurance policy of the country. In conclusion, we suggest the cutpoints
      for borderline-high and high serum cholesterol levels as 200 and 240 mg/dL,
      respectively.

PMID- 9142656
TI  - Increased expression of urokinase type plasminogen activator(u-PA), plasminogen
      activator inhibitor-1(PAI-1), and collagenases in Caco-2 cells infected by
      Salmonella typhimurium.
AB  - Salmonella penetrates the basement membrane of intestinal epithelial cells into
      deeper tissues, in which process extracellular matrix proteases should be
      required. Hypothesizing that the proteases might be provided by host cells, we
      investigated the changes of expression of urokinase type plasminogen activator(u
      PA), plasminogen activator inhibitor-1(PAI-1), and collagenases in epithelial
      cells(Caco-2) infected with Salmonella typhimurium. The change of mRNA levels,
      amount of the enzyme secretion and functional activity were analyzed by Northern
      blot, ELISA, and Zymography. The mRNA level of u-PA was elevated by Salmonella
      infection itself without any exogenous transcription regulators. u-PA was
      actively secreted into the medium and was enzymatically active. The synthesis and
      secretion of PAI-1 was increased over time from 2 hrs post infection(pi) to 8 hrs
      pi. Zymographic assay revealed that the secretion of collagenases (type IV, type
      V and interstitial collagenase) were also increased. Taken together, S.
      typhimurium infection might induce accumulation of pericellular proteolytic
      activity and consequently degrade the extracellular matrix surrounding the
      infected cells. These in turn might enable Salmonella to invade into deeper
      tissues.

PMID- 9142657
TI  - Serum insulin-like growth factors (IGFs) and IGF binding protein (IGFBP)-3 in
      patients with gastric cancer: IGFBP-3 protease activity induced by surgery.
AB  - Recent findings have indicated that insulin-like growth factors (IGF-I and IGF
      II) may play a role in neoplasia. Alteration of serum IGFs or IGF Binding
      Proteins (IGFBPs) have been reported in some tumors. In this study, we measured
      serum IGF-I, IGF-II and IGFBPs profile in gastric cancer by radioimmunoassay and
      Western ligand blots. The serum IGF-I level in gastric cancer was significantly
      lower than in control subjects (65.2 +/- 26.5 vs 148.4 +/- 55.2 ng/ml, p < 0.01)
      and was further decreased to 45.5 +/- 20.9 ng/ml after surgery. The serum IGF-II
      level was slightly higher than that in control subjects (826.3 +/- 360.2 vs 735.7
      +/- 154.6 ng/ml) but it was significantly decreased after surgery (525.7 +/-
      220.1 ng/ml, p < 0.05). The serum IGFBP-3 level was not significantly different
      from those in control subjects. However, we observed a decreased level of serum
      IGFBP-3 after surgery, and incubation of postoperative serum with control serum
      resulted in a significant reduction of IGFBP-3 level. The reduction of IGFBP-3 in
      postoperative serum was mainly due to surgery associated IGFBP-3 protease
      activity. This protease activity was totally inhibited by aprotinin, EDTA and
      PMSF but not by pepstatin and leupeptin. This inhibition pattern is consistant
      with cation dependent serine protease. We speculate that proteolysis of IGFBP-3
      may contribute to increase the bioavailability of IGFs.

PMID- 9142658
TI  - Management of urinary calculi in pregnant women.
AB  - The incidence and predisposing factors of urinary calculi are generally the same
      in both pregnant and non pregnant women, but anatomic changes during pregnancy
      make diagnosis and treatment a more challenging issue. We reviewed 16 patients
      (22 stones) of urinary stone during pregnancy between 1986 and 1996 at Kyung Hee
      Medical Center. The most common symptom was flank pain, seen in 81.3% of
      patients, while 68.8% of patients were displayed microscopic hematuria. In all
      cases, diagnosis was made by abdominal ultrasound, there was no need for other
      harmful investigate procedures. Forty point nine percent of the total stones
      (9/22) were passed spontaneously, double J stenting was carried out in three
      cases because of persistent pain or urinary tract infection (UTI), ureteroscopic
      stone removal was performed in one case. Based on our experience and a review of
      the literature, abdominal ultrasound should be performed first and in all cases
      appears sufficient for the diagnosis of a stone. In case of persistent pain or
      urinary tract infection, a double J stent is more effective than percutaneous
      nephrostomy.

PMID- 9142659
TI  - Head-up tilt test in complicated neurocardiogenic syncope in children.
AB  - To confirm the usefulness of head-up tilt test (HUT) in neurocardiogenic syncope
      (NCS) with complicating clinical features, retrospective analysis were done on 12
      selected children. The age at onset was 12.7 +/- 1.9 (mean +/- SD) years.
      Associated clinical features were postoperative congenital heart disease (PO CHD)
      in 3, coexistent arrhythmia in 8 (persistent ventricular arrhythmia during
      exercise in 3, premature ventricular contractions in 2, ventricular couplets in
      1, sinoatrial exit block in 1 and resting sinus bradycardia in 1) and ST segment
      depression during exercise in 1. Four of them had a history of exercise-related
      syncope. All 3 patients with PO CHD had arrhythmia (ventricular tachycardia in 1,
      sinus bradycardia in 1 and atrioventricular block in 1). HUT provoked NCS in 8 (2
      during baseline tilt, 6 during isoproterenol infusion). In one each, ventricular
      tachycardia and loss of consciousness without hypotension and bradycardia were
      induced. Atenolol was tried in 5 with improvement of NCS in 4 and aggravation of
      dizziness in 1. During follow-up, 7 became asymptomatic (2 with atenolol) and 5
      were stationary. In conclusion, HUT was valuable in diagnosing NCS even in
      children with complicating clinical features such as arrhythmias or PO CHD. HUT
      could be done as apart of initial diagnostic tests if the past history suggests
      NCS, regardless of associated clinical features. In some cases, the unexpected
      results of the test turned out useful in managing children with syncope or
      dizziness.

PMID- 9142660
TI  - Abnormal morphological patterns of the left ventricular myocardium in the
      critical stenosis of the aortic valve and the intact ventricular septum.
AB  - The evaluation of prognostic factors in infants with critical stenosis of the
      aortic valve and intact ventricular septum is often misleading due to a complex
      interaction among lesions in the mitral and aortic valves, and the left
      ventricular myocardium. The clinical parameters on the left ventricular function,
      such as ejection fraction and left ventricular end-diastolic volume, are of
      particular interest as their effects on survival are very controversial. We
      performed a clinicopathologic analysis of two autopsied cases of this disease.
      Besides the morphological hallmarks of the aortic and mitral valves, these two
      cases showed two extreme types of pathology in the left ventricular myocardium,
      which might have significant impacts on the clinical evaluation of the left
      ventricular function. Case 1 showed endocardial fibroelastosis associated with
      abnormal intertrabecular spaces (so-called spongy myocardium), obscuring accurate
      estimation of the left ventricular end-diastolic volume. Case 2 showed ischemic
      necrosis of the apical part of the left ventricular myocardium. This infarct was
      associated with acute and chronic subendocardial ischemia and mild endocardial
      fibroelastosis. Aggravation of the left ventricular failure could be caused by
      the recent ischemic insult. The evaluation of the left ventricular function,
      therefore, should include the evaluation of the morphologic status of the
      myocardium as regards to whether there is ischemia, endocardial fibroelastosis or
      hypertrophied trabeculae in addition to stenotic lesions in the aortic and mitral
      valves.

PMID- 9142661
TI  - Congenital aglossia with situs inversus totalis--a case report.
AB  - Hypoglassia or aglossia is an uncommon anomaly, either of which may occur as an
      isolated finding or in association with other deformations, especially limb
      anomalies. Their genetic background is uncertain, and drug induced teratogen has
      not been clearly identified. We experienced a case of congenital aglossia with
      situs inversus in a female infant aged twelve days. Her initial complaints at
      admission were feeding difficulty and weight loss. In a review of literature, the
      association with situs inversus is very rare and only three cases have been
      reported until now.

PMID- 9142662
TI  - Calcifying fibrous pseudotumor of mediastinum--a case report.
AB  - This report presents a case of calcifying fibrous pseudotumor arising in the
      posterior mediastinum of a 54-year-old woman. The histopathologic features of
      this case were identical to that of calcifying fibrous pseudotumor first
      designated in 1993. It is a distinctive benign fibrous lesion characterized by
      the presence of characteristics psammomatous or dystrophic calcification,
      abundant hyalinized collagen and lymphoplasmacytic cell infiltrate.
      Immunohistochemically most of the scattered fibroblasts were positive for
      vimentin, but not for CD-34 and cytokeratins, distinguishing it from solitary
      fibrous tumor of pleura and desmoplastic mesothelioma. The unusual site of the
      posterior mediastinum and the old age characterize this case.

PMID- 9142663
TI  - Carcinoma ex pleomorphic adenoma of the palate--a case report.
AB  - A case of squamous cell carcinoma ex pleomorphic adenoma in a palate is presented
      and comments on diagnostic criterias are described. The patient was 36-year-old
      male presenting with an ovoid elevated palate mass for 6 months. The tumor
      located in the junctional area of soft and hard palate. The mucosa was diffusely
      ulcerated and the mass focally tightly adherent to adjacent tissue. The initial
      cytologic and pathological diagnosis by fine needle aspiration biopsy and open
      biopsy was benign pleomorphic adenoma. After total removal, histologic
      examination revealed that tumor was composed partly of benign pleomorphic adenoma
      and partly of an squamous cell carcinoma component with areas of necrosis and
      capsular invasion. Immunohistochemical staining in the carcinoma area revealed
      positive reaction for low and high molecular weight cytokeratin, and epithelial
      membrane antigen, but negative for desmin, actin, GFAP and S-100 protein. In situ
      hybridization using biotinylated Epstein-Barr virus probe was done and the
      neoplastic cells were negative. Our case in an unusual partially encapsulated
      carcinoma ex pleomorphic adenoma in the palate and is not related in EBV
      infection.

PMID- 9142664
TI  - Secondary penile carcinoma originated from pancreas.
AB  - Secondary penile cancers are rarely seen and most of them are originated from
      genitourinary and gastrointestinal tract. But metastatic penile cancer originated
      from pancreas are extremely rare and two cases have been reported in the
      literature, only one of them was pathological proven in autopsy. We report a case
      of secondary penile carcinoma originated from the pancreas as the primary site
      which was pathologically proven.

PMID- 9142665
TI  - Poorly differentiated ("insular") carcinoma of the thyroid gland--two cases
      report.
AB  - Poorly differentiated ("insular") carcinoma of the thyroid shares insular,
      trabecular, and solid histological patterns that are different from those of
      papillary, follicular, medullary, and anaplastic varieties. This tumor is
      situated morphologically and biologically in the intermediate position between
      the well differentiated (papillary and follicular) and the totally
      undifferentiated (anaplastic) thyroid tumors. We report two cases of insular
      carcinoma of the thyroid, occurring in 39-year-old and 52-year-old women.
      Grossly, these cases showed a lobulated mass with fibrous septa. The histologic
      finding showed characteristic "insular" growth pattern with focal follicular or
      papillary areas. Thyroglobulin was demonstrated within cytoplasmic paranuclear
      vacuoles of the neoplastic cells. Calcitonin and amyloid were not demonstrated.
      The aspiration cytology showed high cellularity, low grade of atypia, presence of
      clusters, nests, and trabeculae of cells with poorly outlined cytoplasm. The
      ultrastructural finding showed primordial cells having cytoplasmic organelles
      such as rough endoplasmic reticulum, mitochondria, and free ribosomes. We believe
      that its separation from other types of thyroid carcinoma will lead to a more
      accurate estimate of its biologic behavior and a more appropriate therapeutic
      approach.

PMID- 9142666
TI  - Cardiac tamponade as an initial manifestation of systemic lupus erythematosus-
      single case report.
AB  - We describe a case of pericardial tamponade as an initial manifestation of
      systemic lupus erythematosus (SLE). Although pericarditis or pericardial effusion
      is the common cardiac complication of SLE, tamponade is unusual. Treatment
      consists of pericardiocentesis, administration of high dose glucocorticoid an
      antimalarial drug.

PMID- 9142667
TI  - Purely epithelioid malignant peripheral nerve sheath tumor of the vulva.
AB  - Primary malignant peripheral nerve sheath tumors(MPNST) of the vulva are
      extremely rare and most of them are composed of a spindle cell component. A few
      cases of MPNST containing partially or purely epithelioid cells have been
      reported. Purely epithelioid MPNST differ from the ordinary epithelioid MPNST due
      to the absence of a spindle cell component. We present the first case of purely
      epithelioid MPNST arising in the vulva reviewing in the world literature without
      definite evidence of von Recklinghausen's disease or nerve involvement. The
      patient was a 63-year-old woman with a palpable vulvar mass, 6 x 4 x 1.5 cm in
      dimension, was not encapsulated but well-demarcated, ovoid and rubbery and showed
      pale yellow, homogeneous, fish-flesh appearance with focal cystic changes on cut
      surface. The histologic features consisted of solely epithelioid cells which were
      arranged in tight clusters or cords with solid growing pattern and focally
      scattered rosette-like structures. According to the immunohistochemical results,
      most of tumor cells were strongly positive for neuron specific enolase, and some
      of them were weakly positive for S-100 protein and vimentin. We considered that
      purely epithelioid MPNST would represent a certain degree of differentiation
      toward nerve or neuronal cells rather than Schwann cells.

PMID- 9142668
TI  - Impact of HIV risk and infection and the role of prevention services.
AB  - Blood-borne infection associated with injection drug use is a significant cause
      of morbidity and mortality. Over the last decade, HIV infection and its clinical
      sequelae have had a significant impact on research and interventions involving
      injecting drug users (IDUs) in the United States and elsewhere. Discussed are
      some of the major intervention options for reducing blood-borne infections in
      general and HIV in particular. The use of multiple interventions is considered
      within the community context in which both IDUs and service providers operate.
      Intervention options discussed include treatment for drug dependence; voluntary
      and confidential HIV testing and counseling; community health outreach; bleach
      distribution; and easy, legal access to needles and syringes through pharmacy
      sales and needle exchange programs. Many surveillance and evaluative studies have
      examined multiple intervention efforts that include all or some of these program
      components and suggest positive outcomes. However, these studies tend to be
      limited by experimental designs that restrict attribution of causal inference.
      Examples of such programs in the United States and abroad are examined in terms
      of their potential for reducing HIV risk behaviors and averting new infections.
      The article concludes that diversity among AIDS prevention programs, rapid
      deployment (at earlier stages of epidemics), and effective coordination
      (minimization of interagency conflicts) are important factors in successful AIDS
      prevention programming and attaining disease prevention objectives.

PMID- 9142669
TI  - Impact of HIV risk and infection on delivery of psychosocial treatment services
      in outpatient programs.
AB  - HIV risk and HIV infection have profoundly affected the delivery of psychosocial
      treatment services in outpatient drug treatment settings. First, HIV has changed
      the programmatic emphasis of outpatient treatment, from the intake process
      through the goals of care, and treatment program staff are being altered
      significantly. Second, HIV brings with it a pull to extend the reach of drug
      abuse treatment to the sexual partners and families of patients. Finally, for
      community and statewide planners, a debate is emerging between the idea that
      programs should provide high-quality services to a few targeted "high risk" or
      "vital category" patients versus providing minimal services to as many drug
      abusers as possible. There is a vital need for research studies that will add
      data to the decision-making process, at both the policy and programmatic levels.

PMID- 9142670
TI  - The impact of HIV infection on medical services in drug abuse treatment programs.
AB  - The HIV/AIDS epidemic has had a profound impact on the organization and delivery
      of clinical services in drug abuse treatment programs. The need for emphasis on
      HIV prevention vs. treatment services has varied with the geographic distribution
      of HIV infection among drug injectors. On-site primary medical care services have
      been developed in some treatment programs, whereas other programs have had to
      formalize arrangements for referral or contractual care with outside medical
      providers. No single model of care is necessarily appropriate for all drug
      treatment programs, and, along with the potential benefit, each may pose
      structural challenges that need to be addressed. The advent of the AIDS epidemic
      may have served, in an inadvertently positive way, to draw attention to the
      increasingly illogical separation between drug abuse treatment and the larger
      medical care system. This review will examine the epidemiologic, clinical,
      organizational, and policy issues generated by the increased medical needs of
      drug users with HIV infection in treatment program settings.

PMID- 9142671
TI  - Therapeutic communities: AIDS/HIV risk and harm reduction.
AB  - The limited survey data available suggest that therapeutic communities have
      increasingly organized themselves to develop HIV prevention programs and to
      integrate HIV-infected and AIDS clients into the treatment community while
      providing specialized program as necessary. Nonetheless, there remains a need for
      a comprehensive survey of the response of therapeutic communities to AIDS and the
      risk of HIV infection. There is need as well for studies that can build on
      findings linking retention in the therapeutic community to strategies that focus
      on clients' motivation or readiness for treatment. In addition, therapeutic
      community programs can ally with outreach programs both to provide priority
      admission to seropositive clients, women with children, adolescents, and criminal
      justice clients, and to provide harm reduction services to those unwilling to
      enter treatment while also taking incremental steps to engage those clients in
      ever increasing behavior change initiatives.

PMID- 9142672
TI  - HIV risk reduction and service delivery strategies in criminal justice settings.
AB  - Because of the HIV risk behaviors of substance abusers, particularly injection
      drug users and those who exchange sex for drugs, and the large numbers who are
      already infected with HIV or showing symptoms of AIDS, significant service
      delivery issues are associated with their criminal justice processing. Many
      strategies have been implemented in correctional settings in an effort to prevent
      and control the transmission of HIV. A number of these are for the purpose of
      lowering transmission risk in institutions, whereas others have been structured
      for the sake of offering prevention/intervention to inmates before they return to
      the free community. As such, prisons and jails represent opportune settings for
      HIV prevention and education. The most common HIV control/prevention/education
      strategies include mandatory testing of inmates for HIV, segregating infected
      inmates from the general prison population, establishing special health care
      units for HIV positive and AIDS symptomatic inmates, offering HIV prevention and
      risk reduction programs, and granting medical parole for the terminally ill.
      Because drug abuse treatment results in substantial declines in the use of
      heroin, cocaine, and other drugs, treatment per se can play a significant role in
      reducing the spread of HIV and AIDS among those coming to the attention of the
      criminal justice system. Most promising are continuous and integrated treatment
      services that are tied to the stages of correctional supervision: primary
      treatment while incarcerated; secondary treatment while on work release, halfway
      house or community supervision; and, tertiary treatment in ongoing aftercare.

PMID- 9142674
TI  - Consensus statements from conference on AIDS/HIV infection and drug abuse
      treatment.

PMID- 9142673
TI  - Substance abuse treatment and HIV services: Massachusetts' policies and programs.
AB  - States and communities use many strategies and policies to facilitate the
      integration of HIV and AIDS services with alcoholism and drug abuse treatment and
      prevention programs. Massachusetts' policy initiatives that promoted
      collaboration between substance abuse programs and AIDS services are outlined.
      The review begins with an overview of the HIV epidemic in Massachusetts and
      reflects on the initial challenges of building system capacity so that HIV and
      substance abuse services could become more closely integrated. The discussion
      summarizes specific policy strategies implemented to encourage system development
      and to develop program and staff skills for working with men and women with
      HIV/AIDS and at risk of infection. The initiatives included integration of
      alcoholism and drug abuse treatment programs, expansion of Medicaid reimbursement
      for substance abuse treatment, training and skills development for counselors,
      and coordinated service development and advocacy for substance abuse and
      development for counselors, and coordinated service development and advocacy for
      substance abuse and AIDS/HIV services.

PMID- 9142675
TI  - Neointimal hyperplasia following argon ion laser carotid endarterectomy: with and
      without endothelial cell seeding.
AB  - BACKGROUND AND OBJECTIVE: This study compares the development of neointimal
      hyperplasia following conventional and argon ion laser carotid endarterectomy and
      assesses the potential advantage of endothelial cell seeding. STUDY
      DESIGN/MATERIALS AND METHODS: Eight dogs underwent conventional endarterectomy in
      one carotid artery and an argon ion laser endarterectomy in the other. After 42
      days, these arteries were harvested and the intimal thickness were compared. Six
      additional dogs underwent bilateral argon ion laser carotid endarterectomy with
      endothelial cell seeding on the one side only. These arteries were harvested
      after 65 days and their mean intimal thickness were compared. RESULTS: At 42
      days, the mean intimal thickness in the conventional endarterectomy group was
      0.070 +/- 0.007 mm; in the argon ion laser endarterectomy group it was 0.058 +/-
      0.001 mm (P = 0.76, NS). At 65 days, the mean intimal thickness in the group
      without endothelial cell seeding was 0.125 +/- 0.003 mm vs. 0.061 +/- 0.001 mm on
      the seeded side (P = 0.043). CONCLUSION: Argon ion laser carotid endarterectomy
      results in no more neointimal hyperplasia than conventional endarterectomy. The
      neointimal hyperplasia is reduced by endothelial cell seeding.

PMID- 9142676
TI  - In vivo intravascular laser photodynamic therapy in rabbit atherosclerotic
      lesions using a lateral direction fiber.
AB  - BACKGROUND AND OBJECTIVE: This study was performed to evaluate the possibility of
      inducing regression of atherosclerotic foci by photodynamic therapy (PDT) using
      hematoporphyrin derivative (HpD). STUDY DESIGN/MATERIALS AND METHODS:
      Atherosclerotic rabbits were divided into four groups: A (n = 6) and C (n = 6)
      were given 5 mg/kg of HpD intravenously; Groups B (n = 4) and D (n = 4) were not.
      Twenty-four hours after HpD administration, the aortae of groups A and B were
      exposed to 200 mw output argon dye laser beam at 630 nm for 10 minutes; groups C
      and D were exposed to 400 mw for 5 minutes. Three rabbits from groups A and C and
      two rabbits from groups B and D were sacrificed immediately after laser
      photoradiation, being named groups A 0, C 0 and groups B 0, D 0, respectively.
      Groups A 7, C 7, and Groups B 7, D 7 were sacrificed 7 days after the
      photoradiation. RESULTS: In groups A 7 and C 7, most intimal cells and
      endothelial cells had become necrotic and disappeared, and a loss of intima was
      observed. No such changes were found in groups B 7, D 7. CONCLUSION: The above
      data suggest that PDT caused effective regression of the atherosclerotic lesions.

PMID- 9142677
TI  - Single-laser approach for fluorescence guidance of excimer laser angioplasty at
      308 nm: evaluation in vitro and during coronary angioplasty.
AB  - BACKGROUND AND OBJECTIVE: Spectroscopic guidance of laser angioplasty has been
      attempted using a diagnostic He-Cd laser in addition to the therapeutic laser
      system. This study evaluated a single-laser approach for simultaneous ablation
      and fluorescence excitation. STUDY DESIGN/MATERIALS AND METHODS: A spectroscopy
      system was coupled to a clinical XeCl excimer laser. Ablation of 162 human aortic
      samples in saline and blood with 45 mJ/mm2 per pulse yielded 676 fluorescence
      spectra validated histologically. The same equipment was used in 16 patients for
      angioplasty of 18 coronary stenoses applying 500 to 1,725 pulses with 45 to 60
      mJ/mm2 under saline flushing. A total of 783 spectra were recorded and validated
      by intracoronary ultrasound (categories: atheroma, fibrous plaque, calcified
      lesion). RESULTS: In vitro, 5 types of spectra could be differentiated: (1)
      atheroma, (2) fibrous plaque, (3) calcified lesion in saline, (4) media, and (5)
      calcified lesion in blood. Discriminant analysis prospectively classified 576
      validation spectra with the following sensitivity and specificity for each type:
      (1) 83.5 and 97.1%, (2) 85.7 and 96.8% (3) 100 and 98.5%, (4) 98.1 and 99.3%, (5)
      98.9 and 100%, respectively. In vivo type 1, 2, 3, and 5 spectra were also
      observed, but not the media spectrum. The predominant sonographic category also
      prevailed in spectroscopy. Calcified lesions yielded type 3 and 5 as well as
      mixed spectra. CONCLUSIONS: Using an excimer laser for angioplasty allows
      combining ablation and fluorescence excitation without a diagnostic laser.
      Principal types of atherosclerotic lesions and the media can be differentiated
      spectroscopically with this approach.

PMID- 9142678
TI  - Microendoscopic treatment of the hypopharyngeal diverticulum with the CO2 laser.
AB  - BACKGROUND AND OBJECTIVE: The hypopharyngeal (Zenker's) diverticulum is a
      herniation of mucosa and submucosa on the posterior wall of the pharynx. The only
      treatment is surgical. STUDY DESIGN/MATERIAL AND METHODS: Between 1976 and 1993,
      109 patients with a hypopharyngeal diverticulum were operated on at the
      Department of Otorhinolaryngology, Head and Neck Surgery, University of Kiel,
      either transcutaneously combined with a cricopharyngeal myotomy (n = 76), or
      microendoscopically (n = 37) using the CO2 laser. Results and complications of
      both techniques were evaluated and compared. RESULTS: With both surgical
      procedures, > 90% of the patients were treated successfully. The rate of
      postoperative complications was generally low. In comparison to the
      microendoscopic procedure, serious complications were found to be more frequent
      in patients treated with the conventional transcutaneous diverticulectomy.
      CONCLUSION: The laser surgical tissue bridge dissection is a less invasive,
      quick, relatively safe, and effective procedure requiring only short
      hospitalisation. Therefore, the laser surgical tissue bridge dissection can be
      considered as the method of choice for the treatment of the hypopharyngeal
      diverticulum.

PMID- 9142679
TI  - Clinical evaluation of a method for detecting superficial surgical transitional
      cell carcinoma of the bladder by light-induced fluorescence of protoporphyrin IX
      following the topical application of 5-aminolevulinic acid: preliminary results.
AB  - BACKGROUND AND OBJECTIVE: In bladder cancer, conventional white light endoscopic
      examination of the bladder does not provide adequate information about the
      presence of "flat" urothelial lesions such as carcinoma in situ. In the present
      investigation, we examine a new technique for the photodetection of such lesions
      by the imaging of protoporphyrin IX (PpIX) fluorescence following topical
      application of 5-aminolevulinic acid (ALA). STUDY DESIGN/MATERIALS AND METHODS:
      Several hours after bladder instillation of an aqueous solution of ALA in 34
      patients, a Krypton ion laser or a filtered Xenon arc-lamp was used to excite
      PpIX fluorescence. Tissue samples for histological analysis were taken while
      observing the bladder wall either by means of a video camera, or by direct
      endoscopic observation. RESULTS: A good correlation was found between the PpIX
      fluorescence and the histopathological diagnosis. On a total of 215 biopsies, 143
      in fluorescent and 72 in nonfluorescent areas, all visible tumors on white light
      cytoscopy appeared in a bright red fluorescence with the photodetection
      technique. In addition, this method permitted to discover 47 unsuspected
      carcinomatous lesions on white light observation, among which 40% were carcinoma
      in situ. CONCLUSION: PpIX fluorescence induced by instillation into the bladder
      of 5-ALA is an efficient method of mapping the mucosa in bladder carcinoma.

PMID- 9142680
TI  - Thermal modelling of micropulsed diode laser retinal photocoagulation.
AB  - BACKGROUND AND OBJECTIVE: Recent studies have sought to utilize diode laser
      "micropulsing" in order to preserve therapeutic efficacy of retinal
      photocoagulation while minimizing pain and subjacent tissue injury. A model for
      the transient thermal tissue response to continuous and micropulsed diode laser
      output is presented in order to understand the laser-tissue interactions and to
      generate optimum parameters for exploiting potential advantages of micropulsed
      application. STUDY DESIGN/MATERIALS AND METHODS: The tissue thermal response was
      calculated by convolving the analytical solution to the three-dimensional,
      isotropic heat conduction equation with a source term corresponding to the spot
      size of the laser incident on the absorbing retinal pigment epithelium (RPE) and
      choroid layers of the ocular fundus. Thermal localization is quantitated by
      comparing the temperature rise in the RPE (T(RPE) and deep choroid (T(Ch). A 1
      watt (average power), 20-microns diameter, 100 ms pulse (continuous or
      micropulsed) of 810 nm radiation was modelled to be incident on a geometric
      idealization of the human retina and choroid. RESULTS: A temperature gradient is
      rapidly established with only modest temperature augmentation between 10 and 100
      ms. At 100 ms T(RPE) and T(Ch) are 32 and 23 C, respectively, for continuous
      application, and 41 and 27 C for 2 ms on/off micropulsed application. For a duty
      factor (total laser "on" time divided by pulse length) of 50%, T(RPE)/T(Ch) is
      maximal for a micropulse on/off duration of 2 ms; however, the variation over
      micropulse durations from 200 microseconds to 50 ms is small. In addition,
      whereas end-pulse T(RPE)/T(Ch) is greater for 2 ms on/off application when
      compared with continuous delivery (1.53 vs. 1.39), thermal relaxation during
      pulse quiescence in the micropulsed mode allows for an early increase in deep
      choroidal temperature with respect to T(RPE). For ten 200 microseconds pulses
      equally separated over 100 ms (duty factor = 2%), T(RPE)/T(Ch) = 3.2. With more
      numerous, lower power micropulses, T(RPE)/T(Ch) decreases monotonically to 1.39
      as the duty factor is increased to 100%. CONCLUSION: These modelling studies
      provide the first quantitative predictions of thermal localization achieved with
      diode laser micropulsing and demonstrate that short pulse lengths and low duty
      factors allow for maximum thermal localization. These studies will potentiate
      pulse-shape optimization strategies for diode laser retinal photocoagulation
      applications.

PMID- 9142681
TI  - Intraocular measurements of pressure transients induced by excimer laser ablation
      of the cornea.
AB  - BACKGROUND AND OBJECTIVE: The evolution of pressure waves induced by argon
      fluoride laser ablation of the cornea in the typical operative conditions of
      clinical laser keratectomy has been studied experimentally and analyzed.
      MATERIALS AND METHODS: Freshly enucleated porcine eyes were irradiated at a laser
      fluence of 180 mJ/cm2 with various spot diameters in the range 1-6.5 mm. Pressure
      transients were detected by a fast rise time needle hydrophone inserted into the
      eyeball from the posterior pole and moved along the eye optical axis toward the
      cornea. RESULTS: Pressure peaks as high as 90 bar and 50 ns pulse duration (FWHM)
      were measured in the anterior chamber. Observation of the pulse shape evolution
      during propagation put in evidence the onset of a marked rarefaction phase
      following the compressional spike, with intense negative peaks (up to -40 bar)
      located at increasing distances from the corneal surface for increasing spot
      diameters. CONCLUSIONS: This behavior was explained by means of simplified models
      describing pressure pulse generation and diffraction effects occurring during its
      propagation. Implications to clinical procedures, as possible damages due to
      tissue stretching and cavitation formation, are also discussed.

PMID- 9142682
TI  - Effects of low-energy gallium-aluminum-arsenide laser irradiation on cultured
      fibroblasts and keratinocytes.
AB  - BACKGROUND AND OBJECTIVE: To assess whether the gallium-aluminum-arsenide low
      energy laser will increase cell proliferation, cell attachment, or cell migration
      in cultured fibroblasts and keratinocyte models. STUDY DESIGN/MATERIALS AND
      METHODS: Monolayer cultures of fibroblasts and keratinocytes were subjected to
      gallium-aluminum-arsenide laser irradiation at varying power densities for
      varying time intervals. Cell proliferation was assessed by absorbent
      spectrophotometry while cell adhesion was assessed by a microcolorimetric assay
      for cells attached to bovine dermis collagen. Cell migration was assessed through
      a filter utilizing high power microscopic fields. RESULTS: There were no
      differences in cell proliferation, adhesion, or migration in either the
      fibroblasts or keratinocyte culture treated with the gallium-aluminum-arsenide
      laser at any power density or time compared with nontreated controls. CONCLUSION:
      The gallium-aluminum-arsenide laser, when utilized at powers 5-100 milliwatts and
      times of between 10-120 seconds has no biostimulatory effects on fibroblasts or
      keratinocyte cultures as assessed by cell proliferation, adhesion, or migration.

PMID- 9142683
TI  - Intracorporeal lithotripsy with the Alexandrite laser.
AB  - BACKGROUND AND OBJECTIVE: The objective of this study was to evaluate clinical
      use of an Alexandrite laser lithotripter for intracorporeal lithotripsy of
      urinary calculi. STUDY DESIGN/MATERIALS AND METHODS: We prospectively evaluated a
      flash lamp pumped, Q-switched Alexandrite solid-state laser for use in
      conjunction with ureteroscopy (30 cases) or percutaneous nephrolithotripsy (2
      cases). The laser operates at a wavelength of 755 nm in a pulsed mode with pulses
      of 150-800 ns duration at energy settings of 30-80 mJ. RESULTS: The fragmentation
      rate with the Alexandrite laser alone was 50% (16/32). Failure of the laser was
      due to equipment malfunction or technical problems in 11 cases and inability to
      fragment the stone in 5. All cases of failed Alexandrite laser lithotripsy were
      successfully salvaged with alternative modalities of endoscopic stone destruction
      and removal. One intraoperative complication, a ureteral perforation, occurred;
      however, no long-term sequelae related to laser use was documented. CONCLUSION:
      Clinical results with the Alexandrite laser appear to be inferior to those
      reported with Alternative laser systems and other forms of intracorporeal
      lithotripsy. Whereas some of the inadequacies we have noted may be addressed in
      the future by modifications in the unit and delivery systems, we would not
      recommend this device for intracorporeal lithotripsy of urinary calculi in its
      current form.

PMID- 9142684
TI  - Comparative biodistribution of meta-Tetra(Hydroxyphenyl) chlorin in multiple
      species: clinical implications for photodynamic therapy.
AB  - BACKGROUND AND OBJECTIVE: To optimize photodynamic therapy, it is necessary to
      know the distribution of photosensitizer in normal tissue as well as tumors and
      to know how well animal models match human. This study measured the
      biodistribution of meta-Tetra(Hydroxyphenyl) Chlorin (mTHPC) in three species of
      animals and in humans. STUDY DESIGN/MATERIALS AND METHODS: mTHPC was injected
      intravenously into dogs, rabbits, and humans, and drug levels in various tissues
      were determined 6 days later. One dog was perfused with 3 L of saline to remove
      blood trapped within organs. RESULTS: Absolute and relative concentrations of
      drug in specific tissues varied between species and between individuals. There
      was a general pattern of distribution. Highly vascularized tissues had the
      highest levels of mTHPC, not simply due to trapping of blood. mTHPC did not
      localize in bone and did not cross the blood-brain barrier. Humans had much
      higher levels of drug in their plasma and tissues than did animals. CONCLUSIONS:
      First, drug retention varies from one tissue to another. Second, there is
      significant variability from one individual to another, whether animal or human.
      Third, current models cannot accurately predict from animal studies the optimum
      dose for humans. Measurement of photosensitizer level in plasma at time of
      treatment would allow optimal photodynamic dosing.

PMID- 9142685
TI  - In vitro effects and localisation of the photosensitizers m-THPC and m-THPC MD on
      carcinoma cells of the human breast (MCF-7) and Chinese hamster fibroblasts (V
      79).
AB  - BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) is the combination of a
      photosensitizer with laser light to induce preferential destruction of malignant
      cells. In this study two new photosensitizers--5,10,15,20-meta
      tetra(hydroxyphenyl) chlorin (m-THPC) and m-THPC MethoxyPEG2000 derivative (m
      THPC MD)--were tested, both for their dark toxicity, i.e., cytotoxicity in the
      absence of light, and for their light-induced cytotoxicity in mammalian cell
      cultures. STUDY DESIGN/MATERIALS AND METHODS: Cell lines used were MCF-7 (human
      breast carcinoma) and V-79 (Chinese hamster lung fibroblast). After cultivation
      under standard conditions, cells were administered the photosensitizers and 24 hr
      later exposed to various energy levels of laser light at a wavelength of 652 nm.
      Cell survival was monitored using a clonogenic assay and was expressed as the
      surviving fraction of the untreated control. RESULTS: Up to an m-THPC
      concentration of 1 microgram/ml, no dark toxicity was observed; at higher
      concentrations a rapid fall in survival occurred. m-THPC MD showed no dark
      toxicity up to 100 micrograms/ml. In vitro m-THPC was approximately 10 times more
      cytotoxic than m-THPC MD. The MCF-7 and V-79 cell lines displayed similar
      responses to PDT. CONCLUSIONS: Both m-THPC and m-THPC MD are very efficient
      photosensitizers in vitro. Up to the therapeutic dose, neither exhibited dark
      toxicity. There is clinical relevance of the photosensitizers by a large
      therapeutic index.

PMID- 9142687
TI  - Long-term follow-up of cervical intraepithelial neoplasia treated with minimal
      conization by carbon dioxide laser.
AB  - BACKGROUND AND OBJECTIVE: Minimal conization with carbon dioxide laser (CO2) for
      safe diagnosis and treatment of cervical intraepithelial neoplasia (CIN) 1-3 has
      been utilized for 15 years. To evaluate the results of 15 years' follow-up. STUDY
      DESIGN/MATERIALS AND METHODS: Clinical prospective study: 2,903 non-pregnant
      women whose cervicovaginal smear revealed CIN 1-3, confirmed by colposcopy, were
      referred for minimal conization treatment (LMC). This outpatient free-hand
      excision is performed under local anesthesia with a 60-W continuous laser beam
      focused to a 0.1-mm spot size, giving a power density of 165,000 W/cm2. Adjuvant
      cervical curettage is done routinely. RESULTS: Complications after the procedure
      were insignificant. Histopathological investigations revealed invasive carcinoma
      in 1.2% of the minicones. The primary cure rate was 96.1%. In the life table
      analysis of the patients the cumulative risk of recurrence for all forms of CIN
      was 0.89% at year 5, 1.36% at year 10, and 3.02% at year 15. There was no sudden
      onset carcinoma during the follow-up period. CONCLUSION: Minimal conization is a
      safe, effective treatment for CIN and early forms of microinvasive carcinoma.
      Invasive carcinoma can be detected early and should be treated without delay. The
      cumulative risk of developing new CIN is 3.02% at year 15 and there is no risk of
      sudden-onset invasive carcinoma following this procedure.

PMID- 9142686
TI  - Helium-neon laser irradiation is not a stressful treatment: a study on heat-shock
      protein (HSP70) level.
AB  - BACKGROUND AND OBJECTIVE: Helium-neon (He-Ne) laser irradiation has been
      clinically used to reduce chemotherapy-induced mucositis. This work was designed
      to find out if this treatment is stressful at the cellular level by studying its
      effects on the level of the stress-inducible heat shock proteins. STUDY
      DESIGN/MATERIALS AND METHODS: Human desmodontal and mouse L929 fibroblasts were
      irradiated using a 60 mW laser by a single application of 1.5 and 3J/cm2 in
      continuous mode. Heat shock protein level was studied by gel electrophoresis and
      Western blotting using monoclonal antibodies. RESULTS: He-Ne treatment does not
      induce heat shock protein synthesis in human desmodontal nor in mouse fibroblasts
      at the energy densities used in this study. CONCLUSIONS: These results indicate
      that the treatment is not stressful at the cellular level.

PMID- 9142688
TI  - Response of associated oral soft tissues when exposed to Argon laser during
      polymerization of dental resins.
AB  - BACKGROUND AND OBJECTIVE: Polymerization of dental resins with Argon laser
      produces restorations with improved physical properties when compared to
      conventional visible-light polymerization techniques. However, the possibility of
      damaging adjacent soft tissues has not been addressed. STUDY DESIGN/MATERIALS AND
      METHODS: In this study, Argon laser (488/514 nm) was used for the polymerization
      of composite resins to determine effects on the parakeratinized gingiva adjacent
      to both restored and unrestored teeth in six dogs, using 10-, 20-, and 30-second
      polymerization exposures. RESULTS: Gingival tissues removed at 24 hours, 72
      hours, or 5 days revealed desiccated, disrupted, hyalinized connective tissue.
      Tissues exposed for 10 seconds showed minimal change. This minimal degree of
      change was most evident at 72 hours and returned to normal limits at 5 days. The
      20-second exposure produced alterations evident through all time periods. Tissues
      exposed for 30 seconds exhibited necrosis, severe disruption, and vessiculation,
      which was still unresolved at 5 days. CONCLUSION: This study demonstrates that
      clinically relevant Argon laser exposure (10 seconds) of parakeratinized gingiva
      adjacent to teeth undergoing restoration does not cause lasting damage.

PMID- 9142689
TI  - Laser Doppler perfusion imaging: new technique for determination of perfusion and
      reperfusion of splanchnic organs and tumor tissue.
AB  - BACKGROUND AND OBJECTIVE: Several investigations indicated that laser Doppler
      flowmetry on the liver surface reflects relative changes of the total liver blood
      flow. In this study, Laser Doppler Perfusion Imaging (LDI), monitoring the
      surface only, was used for measurements of tissue perfusion of normal and/or
      impaired liver, pancreas, spleen, stomach and intestines, and the blood flow of
      hepatic tumors in rats. STUDY DESIGN/MATERIALS AND METHODS: Eighty Wistar/Furth
      rats were divided into five groups. Group I served as controls. Groups II and III
      underwent ischemic injury of the liver and intestine with or without the
      administration of WEB2170, a platelet-activating factor receptor antagonist.
      Laser-induced photodynamic therapy (PDT) utilizing delta-amino levulinic acid
      sensitization was performed in Groups IV and V. RESULTS: Normal pancreas and
      intestine had a high LDI perfusion value and the liver and stomach exhibited a
      medium perfusion value whereas the perfusion value from the spleen was low.
      WEB2170 improved the reperfusion of the postischemic liver and intestine. An
      immediate decrease in surface blood flow of hepatic tissue treated by laser
      induced PDT and a decreased blood flow in large tumors were observed. CONCLUSION:
      LDI is a useful technique for the measurement of tissue perfusion of various
      splanchnic organs or tumor tissues.

PMID- 9142690
TI  - Laser-assisted removal of a foreign body impacted in the esophagus.
AB  - BACKGROUND AND OBJECTIVE: We reported the use of Holmium-YAG laser in the
      management of a foreign body impacted in the esophagus. STUDY DESIGN/PATIENTS AND
      METHODS: Esophagoscopy was performed on a man with a denture impacted in the
      esophagus. The denture was disimpacted into the stomach and fractured with
      Holmium-YAG laser before removal. RESULTS: The denture was successfully removed
      in three pieces without complications. CONCLUSION: Holmium-YAG laser can be used
      to fragment foreign bodies to aid in their removal.

PMID- 9142691
TI  - Light and electron microscopic immunohistochemistry of the localization of
      adrenal steroidogenic enzymes.
AB  - Recent immunohistochemical studies have revealed the precise localization of the
      enzymes involved in adrenal steroidogenesis. Light microscopical investigations
      showed that cytochromes P450 of cholesterol side-chain cleavage enzyme (P450scc)
      and of 11 beta-hydroxylase (P45011 beta), 3 beta-hydroxysteroid dehydrogenase/
      delta 5-4 isomerase (3 beta HSD), and 21-hydroxylase (P450C21) are localized in
      all the adrenocortical cells, especially in those of the zona fasciculata
      reticularis. 17 alpha-Hydroxylase/C17-C20 lyase (P45017 alpha,lyase) is present
      in the zona fasciculata-reticularis cells of human, bovine, pig, and guinea-pig
      adrenals, but absent in the adrenals of some rodents such as rat, hamster, and
      mouse. Aldosterone synthase (P450aldo) is contained only in the zona glomerulosa
      cells. In the rat adrenal, P45011 beta, which catalyzes the conversion of
      deoxycorticosterone to corticosterone, is localized in the zona fasciculata
      reticularis cells. Electron microscopic investigations demonstrated that P450scc
      and P45011 beta are colocalized in the matrix side of inner mitochondrial
      membrane including cristae, while 3 beta HSD, P450C21, and P45017 alpha, lyase
      are present in the membranes of smooth endoplasmic reticulum (SER). These results
      clearly indicate that aldosterone, the most potent mineralocorticoid, is
      synthesized in the zona glomerulosa cells, and glucocorticoids, such as
      corticosterone and cortisol, are produced in the zona fasciculata-reticularis
      cells. The conversion of cholesterol to pregnenolone and the final steps of
      corticosteroid synthesis occur in the mitochondria, while the intermediate steps,
      leading to the synthesis of deoxycorticosterone or deoxycortisol from
      pregnenolone, take place in the SER membranes.

PMID- 9142692
TI  - Analytical color fluorescence electron microscopy of adrenal cortex.
AB  - The analytical color fluorescence electron microscope (ACFEM) was employed to
      study rat adrenal gland. The lipid droplets of adrenocortical cells emitted
      cathodoluminescence (CL) and this spectrum had two peak wavelengths at 320 and
      430 nm. Administration of hypocholesterolemic drugs, 17 alpha-ethinyl estradiol
      and 4-aminopyrazolo pyrimidine, significantly decreased the CL of 320 nm in all
      three zones of the adrenal cortex. Conversely, in hypophysectomized-rat adrenal
      cortices, the CL of 320 nm significantly increased and that of 430 nm diminished.
      In the ACTH-treated group, CL of 320 nm in the zonae fasciculata and reticularis
      faded up to 2 hours after injection, while that in the zona glomerulosa remained.
      These results suggest that the CL of 320 nm in adrenocortical cells is derived
      from cholesterol ester. The CL analysis by the ACFEM in combination with the cryo
      scanning electron microscopy method can be an alternative to conventional
      histochemical technique in simplicity, specificity, and preservation of the
      ultrastructure.

PMID- 9142694
TI  - Lipoproteins, lipid droplets, lysosomes, and adrenocortical steroid hormone
      synthesis: morphological studies.
AB  - Recent studies concerning cellular cholesterol homeostasis suggest that there is
      a relationship between the serum lipoproteins (low density and high density
      lipoproteins: LDL and HDL), the intracellular storage of cholesterol (lipid
      droplets), lysosomes, and the steroidogenic activity of adrenocortical cells.
      This review surveys the current knowledge on cholesterol import from LDL/HDL by
      adrenocortical cells, its regulation, and the participation of lipid droplets and
      lysosomes in this process. The possible role of adrenocortical cell microvilli in
      the uptake of LDL/HDL is discussed. Under certain physiological, experimental,
      and pathological circumstances lysosomes accumulate unesterified and/or
      esterified cholesterol in the form of lipid-lysosome complexes. As suggested by
      the data presented in this review, lipid-lysosome complexes appear to be involved
      in cholesterol homeostasis, via altering lipid compartmentalization. Since
      previous reports do not clearly demonstrate a positive correlation between the
      volume of lipid- and lysosome-compartments and the rate of steroid hormone
      synthesis [for review, see Nussdorfer (1986) Int. Rev. Cytol., 98:1-405], the
      objective of this review is to provide a better understanding of the interactions
      of plasma lipoproteins, lipid droplets, lysosomes, and steroidogenesis.

PMID- 9142693
TI  - Roles of microfilaments and intermediate filaments in adrenal steroidogenesis.
AB  - The problem for the steroidogenic cell if it is to accelerate steroid synthesis
      in response to trophic stimulation, consists in moving cholesterol from the sites
      of synthesis and storage to mitochondria at an accelerated rate. The most
      intensely studied situation is that in which the sterol is stored as ester in
      lipid droplets. Cholesterol ester must be de-esterified and transported to
      mitochondria where steroid synthesis begins. Since droplets and mitochondria are
      now known to be attached to intermediate filaments and since these structures are
      not contractile, it appears to be necessary to invoke the actions of other
      cytoskeletal elements. Actin microfilaments are involved in cholesterol transport
      so that it is tempting to propose that the contractile properties of actomyosin
      are used in this process. It is known that an energy-dependent contractile
      process involving actin is capable of disrupting intermediate filaments. Since
      the intermediate filaments appear to act by keeping lipid droplets and
      mitochondria apart, disruption of the filaments accompanied by a contractile
      process would be expected to allow these two structures to come together. This
      would open the way for the transfer of cholesterol to the steroidogenic pathway.
      This should be regarded as a first step. The events necessary for entry of
      cholesterol from droplets into the mitochondria remain to be clarified. In
      addition, the transport process for newly synthesized cholesterol that is not
      stored in droplets, is still not understood. At least four protein kinase enzymes
      have been identified in the cytoskeletons of adrenal cells, namely,
      Ca2+/calmodulin-dependent kinase, protein kinase (Ca2+ and phospholipid
      dependent), myosin light chain kinase, and protein kinase A (cyclic AMP
      dependent). The Ca2+/calmodulin kinase promotes transport of cholesterol to
      mitochondria and does so under conditions in which phosphorylation of vimentin
      and myosin light chain occurs. Phosphorylation of vimentin results in disruption
      of intermediate filaments while phosphorylation of light chain promotes
      contraction of the actomyosin ring. It now appears that intermediate filaments
      are cross-linked by actin filaments so that such contraction would be expected to
      produce significant structural changes in the cytoskeleton and the attached
      organelles. Although the details of the changes taking place in the organ in vivo
      are not known, the potential for interaction between droplets and mitochondria as
      the result of these changes in intermediate filaments and actomyosin, is clear.
      Protein kinase C is activated by ACTH and cyclic AMP, although this activation
      does not appear to be directly involved in the regulation of steroid synthesis.
      Nevertheless, vimentin is a substrate for this enzyme, and changes in the
      organisation of vimentin filaments and the attached organelles under the
      influence of protein kinase C have been reported in other cells. Presumably these
      changes represent part of the response to ACTH because when protein kinase C is
      activated by phorbol ester, the cytoskeletal changes necessary for rounding up
      take place but such changes are not accompanied by increased steroid synthesis.
      Protein kinase A causes rounding of adrenal cells. and cytoskeletons. This kinase
      also causes increased cholesterol transport and, hence, stimulation of steroid
      synthesis. The enzyme also causes phosphorylation of vimentin but with a
      different cytoskeletal reorganisation from that seen with the other three kinase
      enzymes. Clearly phosphorylation plays a major role in these responses.
      Phosphorylation alters the morphology and the functions of the cytoskeleton and
      this, in turn, is associated with accelerated cholesterol transport. It is now
      necessary to define the details of the specific phosphorylation reactions that
      occur during the response to ACTH, that is, which amino acids are phosphorylated
      and to what extent by each of the kinase enzymes.

PMID- 9142695
TI  - Peroxisomes in adrenal steroidogenesis.
AB  - Peroxisomes, cytoplasmic organelles limited by a single membrane and with a
      matrix of moderate electron density, are present in a great number of cells,
      namely in adrenal cortex and other steroid-secreting organs. Presently
      peroxisomes are considered to be involved in important metabolic processes. They
      intervene in: (1) the production and degradation of H2O2; (2) biosynthesis of
      ether-phospholipids, cholesterol, dolichol, and bile acids; (3) oxidation of very
      long chain fatty acids, purines, polyamines, and prostaglandins; (4) catabolism
      of pipecolic, phythanic and glyoxylic acids; and (5) gluconeogenesis. Recent
      studies demonstrated that the experimental alterations in the normal
      steroidogenesis, produce significant morphological and biochemical changes in
      peroxisomes. Besides this, the presence of 3-hydroxy-3-methylglutaryl-coenzyme A
      reductase (the key enzyme in the de novo cholesterol synthesis from acetate) and
      of sterol carrier protein-2 (SCP2), which is involved in the cholesterol
      metabolism and steroid metabolic pathways, are located in peroxisomes of steroid
      secreting cells. In addition, patients with peroxisome diseases present
      deficiency in steroidogenesis, as well as reduced levels of SCP2. These data
      pointed out the important role of peroxisomes in steroid biosynthesis.

PMID- 9142696
TI  - Role of the Golgi complex in adrenocortical steroidogenesis.

PMID- 9142697
TI  - Comparison of gap junction expression in the adrenal gland.
AB  - The presence of alpha 1 (Cx43) gap junction protein was demonstrated in rat,
      mouse, guinea pig, and bovine adrenal glands with immunocytochemical techniques.
      The presence of six other connexin species was not detected in the adrenal glands
      studied. The gap junction stain within the adrenal cortex was punctate and
      located at sites of cell-cell contact. While little gap junction, alpha 1,
      staining was detected at sites of cell contact in the zona glomerulosa (ZG), the
      zona fasciculata (ZF) and zona reticularis (ZR) had intense staining at cell
      contacts in all rodent species studies. In the bovine adrenal, ZG cells were
      connected by large gap junctions as were the cells of the ZF and ZR. The
      variations in alpha 1 distribution within the adrenal cortex may correspond with
      the different division rates and hormone functions within the adrenal gland as
      well as species differences between rodent and bovine adrenal gland.

PMID- 9142698
TI  - Morphological and functional studies of the paracrine interaction between cortex
      and medulla in the adrenal gland.
AB  - Within the last years it has become evident that besides the hypothalamo
      pituitary-adrenal axis, extrapituitary mechanisms exist that regulate the
      activity of the adrenal cortex. In this context, intra-adrenal regulatory
      mechanisms play an important role. Several secretory products from
      adrenomedullary cells are able to influence adrenocortical steroidogenesis. Since
      the main blood flow within the adrenal is directed centripetally from the cortex
      to the medulla, chromatin cells should act on cortical cells in a paracrine
      manner. The morphological prerequisite for this regulatory pathway is seen in the
      close apposition of the two tissues. Within the mammalian adrenal, the two
      endocrine tissues are interwoven to an astonishing degree with cortical cells
      located within the medulla and vice versa. It is concluded from morphological and
      functional studies that paracrine interactions between cortex and medulla play an
      important role in the regulation of adrenocortical steroidogenesis.

PMID- 9142699
TI  - Innervation of the adrenal cortex, its physiological relevance, with primary
      focus on the noradrenergic transmission.
AB  - The current knowledge of the catecholaminergic innervation of the mammalian
      adrenal cortex is summarized, and macro- and microscopic neuromorphology,
      including the central nervous system connections of the adrenal cortex, is
      briefly discussed. Morphological and functional data on the catecholaminergic
      (i.e., noradrenergic) innervation of the adrenal cortex are reviewed.
      Experimental data suggest that in addition to the regulation of adrenal blood
      flow, the noradrenergic innervation has a primary influence on zona glomerulosa
      cells possibly via beta 1 adrenergic and dopaminergic receptors (DA2 subtype via
      inhibiting T-type Ca2+ channels) It is concluded that the local, modulatory
      effect of noradrenergic nerve fibres, terminating in the close vicinity of the
      zona glomerulosa cells, on the systemic renin-angiotensin-aldosterone and other
      peptide cascade may be influenced by neuropeptides, particularly neuropeptide Y
      and vasoactive intestinal peptide.

PMID- 9142700
TI  - Vascularization of the adrenal cortex: its possible involvement in the regulation
      of steroid hormone release.
AB  - This review examines the morphology of the adrenal gland with particular
      reference to the adrenal vasculature. It examines the possibility that
      variability in adrenal gland responsiveness may be attributable to neural or
      hormonal modulation of adrenal blood flow. Changes in the rate of blood flow
      through the adrenal cortex would be expected to play an important role in the
      regulation of steroid hormone release. It would affect both the delivery of the
      major stimulant (ACTH) and the removal of the end product from the steroidogenic
      cells (the glucocorticoids). In the past, interest in this area has concentrated
      on the regulation of arterial blood flow, rather than the regulation of venous
      drainage. The current review examines the concept of vascular damming, and
      attempts to link the morphological features of the gland with experimental data
      associated with glucocorticoid release. It is postulated that regulation of
      venous drainage, via the vascular dam, plays an important role in the storage of
      the secretory product during the animals' inactive phase, and in the initial
      rapid rise in plasma levels of the glucocorticoids seen in response to stress or
      injection of ACTH.

PMID- 9142701
TI  - Peptide growth factors and the adrenal cortex.
AB  - Increasing evidence suggests that the actions of classical stimulants of
      adrenocortical growth and function, such as ACTH or dietary sodium restriction,
      may partially be mediated via locally produced regulators. Several peptide growth
      factors, such as basic fibroblast growth factor, insulin-like growth factors, and
      transforming growth factor-beta 1, have emerged in recent years as
      multifunctional molecules that typically play such regulatory roles.
      Adrenocortical cells are highly responsive to these growth factors, in particular
      in the regulation of cell growth and differentiated functions, such as
      steroidogenesis. In addition, growth factor expression in the adrenal cortex has
      been shown to be regulated by physiological stimulants. The spatial expression,
      release, and activation of these growth factors may, therefore, locally mediate
      or amplify the actions of the hypothalamo-pituitary axis and the renin
      angiotensin system on adrenocortical proliferation, differentiation, and
      steroidogenesis.

PMID- 9142702
TI  - The pharmacological armament of pediatric cardiology.

PMID- 9142703
TI  - The pediatric cardiology pharmacopoeia.
AB  - Keeping up with a rapidly growing list of medications has always been a
      breathtaking and, at times, impossible task to master. Contrary to common belief,
      the enormity of keeping abreast with the more recently developed medications is
      not a modern phenomenon resulting from the great technological advances of the
      past few years, but an ongoing struggle spanning the latter half of this century.
      It appears that there are more drugs to use than to know how, when, or what to do
      with them. This sentiment was expressed in 1973 by the editors of Martindale's
      The Extra Pharmacopoeia, twenty-sixth edition [3]: "The unprecedented rate at
      which our knowledge of medicine and pharmacy is advancing makes it a formidable
      challenge to provide within a single volume an up-to-date source of basic
      information on the properties and uses of the many drugs in current use." In this
      article, a review of the medications currently used in the management of children
      with heart diseases is presented. The medications have been collected in groups
      based upon their pharmacological actions: Antiarrhythmic, antihypertensive,
      diuretics, sedatives and miscellaneous agents. Within each group the agents are
      listed alphabetically using chemical names. We attempted to include as many drugs
      as thought to be of relevance to the team of health practitioners involved in the
      care of children with cardiac problems. Various routes of administration are
      presented, some of which have been infrequently described in the pediatric
      literature, such as continuous infusion of diuretic agents [22]. The dosing
      ranges were adopted from many sources [1, 5, 8, 9, 17-19, 22, 23, 26], and we
      sought to include the widest ranges of dosages published. All dosages listed in
      Table 1 are quantitated per dose and not per day. This approach was adopted as it
      reduces calculations and the potential for medication errors.

PMID- 9142704
TI  - Dynamic three-dimensional echocardiographic reconstruction of congenital cardiac
      septation defects.
AB  - Dynamic three-dimensional echocardiographic reconstructions of 27 cardiac
      septation defects were performed in 19 sedated infants and children. Using a
      subxiphoid rotational scanning approach, complete visualization of the entire
      shape and breadth of the defect was attained in 11 of 16 ventricular septal
      defects and 9 of 11 atrial septal defects. This technique enabled the operator to
      cut slices from the three-dimensional block of echocardiographic data in order to
      present septation defects in a region- or lesion-oriented fashion. Poor baseline
      two-dimensional image quality and certain small septation defects that were
      readily obscured by nearby structures led to inadequate three-dimensional
      reconstructions. The application of dynamic three-dimensional echocardiography
      for assessment of cardiac septation defects uniquely provided (1) the ability to
      present en face views of atrial and ventricular septal defects; and (2) a means
      by which intracardiac anatomy can be displayed in a region- and lesion-oriented
      fashion for interventional and surgical planning purposes.

PMID- 9142705
TI  - Lung perfusion patterns after bidirectional cavopulmonary anastomosis (Hemi
      Fontan procedure).
AB  - Perfusion lung scans were performed immediately prior to Fontan procedure in 45
      patients with a functional single ventricle who underwent the hemi-Fontan
      procedure as an intermediate stage between the initial palliative shunt procedure
      and the final complete Fontan anastomosis. Symmetric pulmonary blood flow (PBF)
      distribution was found in 27% of patients, whereas moderately to severely
      abnormal PBF distribution was found in 35% of patients. The achieved systemic
      aortic saturation following the hemi-Fontan procedure was not affected by these
      abnormalities.

PMID- 9142706
TI  - Pharmacologic agents inducing electrocardiac conduction delays.

PMID- 9142707
TI  - Balloon atrial septostomy under two-dimensional echocardiographic control: a new
      outlook.
AB  - Between January 1989 and February 1995 a group of 47 consecutive infants aged 31
      180 days (mean 83.5 +/- 48.8 days) with various cyanotic heart diseases and poor
      intracardiac mixing underwent balloon atrial septostomy (BAS) under two
      dimensional (2D) echocardiographic control in the procedure room or intensive
      care unit. Diagnoses were 27 cases of transposition of the great arteries (TGA),
      1 mitral atresia, 9 tricuspid atresia, 7 critical pulmonary stenosis with
      hypoplastic right ventricle, 3 pulmonary atresia with intact interventricular
      septum, and 1 total anomalous pulmonary venous return. A standard subcostal view
      was used mainly to delineate the interatrial septum and to guide the balloon
      catheter. The creating (tearing) of the atrial septal defect was seen clearly
      during the procedure, and the 2D echocardiographic imaging was helpful for
      assessing the adequacy of the BAS at the end of the procedure. The results were
      good (5-9 mm in diameter) with no significant complications. The 2D
      echocardiographic scans showed no significant changes in the created atrial hole
      sizes during the follow-up of 1-6 months. We conclude that BAS under 2D
      echocardiographic control can be performed successfully and safely in infants
      with cyanotic congenital heart disease up to 6 months of age. This method should
      be considered for palliation, avoidance of surgery, or allowing the patient to
      survive until an appropriate time for corrective surgery.

PMID- 9142709
TI  - Association of fetal junctional rhythm and respiratory arrhythmia detected by
      magnetocardiography.
AB  - Magnetocardiographic recordings from a fetus at 34 weeks' gestation with a
      complex heart malformation revealed an unusual fetal arrhythmia, where the rhythm
      was observed to alternate between extended periods of sinus and junctional
      rhythms. Fetal heart rate measurement showed that the junctional rhythm was
      strongly associated with respiratory arrhythmia. We hypothesize that changes in
      autonomic balance due to the onset and cessation of fetal breathing movements
      were largely responsible for the rhythm alternations. To our knowledge this is
      the first report of a fetal junction rhythm and the first observation of fetal
      respiratory arrhythmia during nonsinus rhythm.

PMID- 9142710
TI  - Incidence of femoral vein occlusion after catheter ablation in children:
      evaluation with magnetic resonance angiography.
AB  - Catheter ablation in children requires placement of multiple large femoral venous
      sheaths and catheters. Magnetic resonance angiography (MRA) was used to evaluate
      the effect of indwelling lines on femoral venous blood flow. Between October 1993
      and February 1994 a total of 17 patients scheduled for catheter ablation
      underwent venous MRA. Two-dimensional time-of-flight MRA was performed 12-70
      hours after catheterization on all patients. All patients received intravenous
      heparin during the procedure and had aspirin therapy instituted after ablation.
      Eighteen catheter ablations and MRA studies were performed on the 17 patients
      (one patient underwent repeat ablation). There were 7 females and 10 males, with
      a mean age of 14.8 +/- 4.2 years (range 8-21 years). Patients had three venous
      sheaths inserted in the left femoral vein (5F, 6F, and 7F with external diameters
      measuring 1.7, 2.0, and 2.3 mm, respectively) and one sheath in the right femoral
      vein (7F). Four patients (22%) had altered venous flow (two complete obstructions
      and two partial obstructions) following catheterization. None of these patients
      experienced symptoms or complications. It was concluded that there is an
      increased incidence (22%) of venous obstruction following catheter ablation, but
      there are no related complications. Venous MRA provides a rapid, noninvasive
      method for evaluating venous flow abnormalities and possibly detects patients at
      risk for complications.

PMID- 9142711
TI  - Angiographic determination of ventricular morphology: correlation with pathology
      in 36 hearts with single functional ventricles.
AB  - Among 36 patients with univentricular atrioventricular connections, 27 had left
      ventricular and 9 right ventricular morphology. None had a common or
      indeterminate ventricle on autopsy review. Angiographic analysis correctly
      determined ventricular morphology in 34 (94%) of 36 patients. All 9 patients with
      right ventricular morphology of the dominant ventricular chamber were correctly
      identified angiographically. Altogether 25 of 27 patients (93%) with left
      ventricular morphology of the dominate ventricular chamber were correctly
      identified angiographically. Two patients with left ventricular morphology and
      severely dilated ventricles were incorrectly classified as having right
      ventricular morphology by angiographic assessment. For patients with a single
      functional ventricle, we conclude that angiographic assessment is an excellent
      method for determining ventricular morphology.

PMID- 9142712
TI  - Circulatory system in children with localized scleroderma.
AB  - The circulatory system was studied in 43 children (ages 3-18 years, mean 10.6
      years; 32 girls, 11 boys) suffering from localized cutaneous forms of
      scleroderma. The following studies were undertaken: general pediatric
      examination, cardiologic examination including routine electrocardiogram (ECG),
      24-h Holter ECG monitoring, echocardiography plus Doppler study, and a treadmill
      exercise test. Three children found to have congenital heart malformations were
      excluded from the study. Children with localized scleroderma were often lighter
      and shorter than their appropriate controls. The most common ECG abnormality was
      incomplete right bundle branch block, but other ECG and Holter abnormalities were
      found as well. Abnormal echocardiographic results were obtained in 16 cases. The
      abnormalities concerned valvar function (in all heart valves but predominantly in
      the mitral valve). It was found that the children suffering from scleroderma had
      different indices than controls for left ventricular mass index, mitral valve
      function and left ventricular filling. During the exercise test (conducted
      according to Bruce's protocol) we found no difference between patients and
      controls.

PMID- 9142713
TI  - Fenestrated fontan procedure: evolution of technique and occurrence of
      paradoxical embolism.
AB  - The Fenestrated Fontan procedure (FFP) has improved outcome in high risk
      patients. The technique is evolving, however, and complications are not fully
      known. Over a 3-year period 13 patients (mean age 35 +/- 29 months) underwent an
      FFP in our institution. In the first two patients the fenestration had to be
      created because of high right atrial pressure and low cardiac output; in 11
      patients the FFP was planned. In three patients the sutures for the adjustable
      fenestration were crossing the defect. In 10 patients, purse-string sutures were
      placed around but not across the defect. Because large fenestrations were created
      in 11 patients (8-12 mm) Glenn shunts were performed to improve arterial
      saturation. The postoperative course was relatively uneventful, with chest tubes
      being removed 1-8 days (mean 4 +/- 3 days) postoperatively and the hospital stay
      ranging from 7 to 27 days (mean 14 +/- 6 days). One patient had bleeding and
      another had a mediastinal abscess. The first patient died (7.6%) because of
      hemodynamic instability due to prolonged cardiopulmonary bypass from the creation
      and enlargement of the fenestration. One patient had a paradoxical cerebral
      embolism from clots that formed on the sutures crossing the fenestration. Because
      of this problem the remaining patients were placed on salicylates while awaiting
      closure of their fenestration. All 12 patients had their fenestrations closed,
      performed under local anesthesia in 9, at mediastinal abscess drainage in 1, and
      spontaneously in 2. We conclude that creation of large fenestrations in
      combination with Glenn shunts and the use of adjustable fenestrations are viable
      modifications of the FFP. The use of purse-string sutures around the fenestration
      and antiplatelet drugs can probably minimize the occurrence of paradoxical
      embolism.

PMID- 9142715
TI  - Dissection of the descending aorta after balloon angioplasty of native
      coarctation.
AB  - A 12-year-old girl underwent successful balloon angioplasty for a waist-like
      native coarctation. The balloon size/coarctation diameter ratio was 3.3.
      Postdilatation angiography showed a small aneurysm at the coarctation site. On
      frequent review the patient remained symptom-free and normotensive.
      Recatheterization was performed 14 months after balloon aortoplasty, when
      angiography revealed a massive aortic dissection extending from the origin of the
      left subclavian artery to both iliac arteries. She underwent partial replacement
      of the thoracic aorta. Balloon angioplasty of a narrow waist-like native
      coarctation may lead to extensive wall dissection and should be considered
      critically.

PMID- 9142718
TI  - Persistent left fifth aortic arch associated with tetralogy of Fallot.
AB  - A case of persistent left fifth aortic arch, forming a congenital "double-lumen"
      aortic arch, has been diagnosed on angiocardiography during life. It appeared as
      an unusual vascular structure running inferiorly and parallel to the "real"
      aortic arch from the innominate artery to the left subclavian artery superior to
      the pulmonary artery. This anomaly was found in the setting of tetralogy of
      Fallot, an association never described before, with patent ductus arteriosus
      (previously reported in most cases). The left aortic arch in this case was not a
      source of pulmonary circulation, as described in previous cases with pulmonary
      atresia and ventricular septal defect, but was a systemic-to-systemic connection
      without functional relevance.

PMID- 9142717
TI  - Cardiac hydatid cyst in a child.
AB  - Cardiac hydatid cyst is a rare disease, especially in children. An 11-year-old
      boy with a previous anaphylactic reaction and episodes of abdominal pain was
      admitted for workup of an acquired long systolic murmur. Echocardiographic
      investigation disclosed a tumor of the right ventricular anterior wall, with
      multiple loculations. Magnetic resonance imaging characterized it as a
      multilobular tumor with cyst formation and disclosed another cyst in the right
      pulmonary artery. With a positive ELISA reaction the child was admitted for
      surgery with the diagnosis of cardiac and pulmonary hydatid cysts. Cardiac
      surgery was performed with good results, followed by medical treatment with
      albendazole.

PMID- 9142719
TI  - Middle aortic syndrome in a boy with arteriohepatic dysplasia (Alagille
      syndrome).
AB  - Middle aortic syndrome is increasingly recognized as a cause of hypertension in
      adolescents and young adults. Alagille syndrome is a genetic disorder
      characterized by hepatic, eye, and bony abnormalities. Cardiovascular lesions
      occur in most of the patients, but narrowing of the abdominal aorta has not been
      previously recorded. We present an unusual association between middle aortic
      syndrome and Alagille syndrome, with a similar vascular lesion seen in two
      generations.

PMID- 9142721
TI  - Radiofrequency catheter ablation of a verapamil-sensitive ventricular
      tachycardia.
AB  - A 14-year-old girl with palpitations was found to have idiopathic ventricular
      tachycardia of right bundle block morphology and superior axis. She was converted
      by intravenous verapamil but was not responsive to oral verapamil therapy. She
      was successfully treated by radiofrequency catheter ablation.

PMID- 9142722
TI  - Tetralogy of Fallot with absent pulmonary valve and bronchial compression:
      treatment with endobronchial stents.
AB  - Absent pulmonary valve syndrome (APVS) is a rare congenital cardiac lesion. The
      lesion includes ventricular septal defect, overriding aorta, and absence of the
      pulmonary valve, with resultant pulmonary incompetence. It has been suggested
      that the pulmonary incompetence induces intrauterine dilatation of the pulmonary
      artery, which leads to tracheobronchial compression. One of the presenting
      features in infants with APVS is severe airway obstruction, which may be
      difficult to manage. We report an infant who benefited from bilateral
      endobronchial endoscopic stent placement.

PMID- 9142723
TI  - Intrapericardial left atrial aneurysm: noninvasive diagnosis.
AB  - Intrapericardial aneurysm of the left atrium is a rare cardiac anomaly. We
      present a 10-year-old girl in whom the diagnosis was made following referral for
      an abnormal configuration of the left heart border seen on chest radiography.
      Diagnosis was made by echocardiography, but magnetic resonance imaging defined
      the exact morphology and the relation to adjacent structures. Surgical removal of
      this aneurysm is recommended because of potentially serious complications.

PMID- 9142724
TI  - Aortic stiffness with the Williams-Beuren syndrome.

PMID- 9142725
TI  - Open heart surgery in the pediatric Jehovah's Witness population: no longer
      "Russian roulette".

PMID- 9142726
TI  - Positron emission tomographic investigations of central muscarinic cholinergic
      receptors with three isomers of [76Br]BrQNP.
AB  - We studied the potential of three radiobrominated isomers of BrQNP, (Z(-,-)
      [76Br]BrQNP, E(-,-)-[76Br]BrQNP and E(-,+)-[76Br]BrQNP), as suitable radioligands
      for imaging of central muscarinic cholinergic receptors in the human brain. These
      radioligands were stereospecifically prepared by electrophilic
      radiobromodestannylation of the respective tributylstannyl precursors using no
      carrier-added [76Br]BrNH4 and peracetic acid. Preliminary pharmacological
      characterizations were determined by biodistribution, autoradiography,
      competition, displacement and metabolite studies in rats. The (-,-)-configuration
      presented important specific uptakes in brain muscarinic cholinergic receptor
      (mAChR)-rich structures and in heart, low metabolization rates and an apparent M2
      selectivity. The (-,+)-configuration revealed more rapid clearance, lower uptake,
      a higher metabolization rate and an apparent M1 selectivity. Reversibility of the
      binding was confirmed for the three radiotracers. Positron emission tomography in
      the living baboon brain revealed high and rapid uptake in the brain and
      accumulation in the mAChR-rich structures studied. At 30 min p.i., the E(-,-)
      radiotracer reached a plateau in cortex, pons and thalamus with concentrations of
      29%, 24% and 19% ID/l, respectively. Z(-,-)-[76Br]BrQNP also accumulated in these
      structures, reaching a maximal uptake (27% ID/l) in the cortex 2 h p.i. At 5 min
      p.i. a plateau (17% ID/l) was only observed in the cortex for the E(-, +)
      [76Br]BrQNP; by contrast, the other structures showed slow washout. After 3
      weeks, the (-,-)-radiotracers were studied in the same baboon pretreated with
      dexetimide (1 mg/kg), a well-known muscarinic antagonist. In all the mAChR
      structures, the highly reduced uptake observed after this preloading step
      indicates that these radiotracers specifically bind to muscarinic receptors. Z(-,
      -)-[76Br]BrQNP, which is displaced in higher amounts from M2 mAChR-enriched
      structures, reveals an M2 affinity. The two isomers having the (-,-)
      configuration are potential probes for investigating central muscarinic
      receptors. The absolute configuration on the acetate chiral centre influences
      their muscarinic subtype selectivity and the cis-trans isomerism of the vinyl
      moiety affects their specific fixation.

PMID- 9142727
TI  - Striatal and extrastriatal imaging of dopamine D2 receptors in the living human
      brain with [123I]epidepride single-photon emission tomography.
AB  - The iodine-123 labelled ligand benzamide epidepride was evaluated as a probe for
      in vivo imaging of striatal and extrastriatal dopamine D2 receptor sites in the
      human brain. Four healthy males were imaged with a high-resolution single-photon
      emission tomography scanner. Striatal radioactivity peaked at 3 h after
      injection. The specific binding in the striatum was 0.91+/-0.03 at 3 h and this
      ratio steadily increased with time. Extrastriatal radioactivity was highest in
      the thalamus, in the midbrain and in the temporal cortex, and peaked at 45-60 min
      after injection of tracer. A smaller amount of radioactivity was found in the
      parietal, frontal and occipital cortices. Two radioactive metabolites were
      observed, of which one was more lipophilic than the parent compound. The
      radiation burden to the patient was 0.035 mSv/MBq (effective dose equivalent).
      The preliminary results showed that [123I]epidepride can be used for imaging
      striatal and extrastriatal dopamine D2 receptor sites in the living human brain.

PMID- 9142728
TI  - Indium-111 labelled lymphocytes: isotope distribution and cell division.
AB  - Since lymphocytes continue to proliferate and divide in vivo, it is important to
      determine the fate of a radionulide following lymphocyte labelling. Using the
      mixed lymphocyte reaction (MLR), we induced indium-111 labelled lymphocytes from
      a specific in-bred rat strain (AS) to divide and then observed the subsequent
      111In distribution between cells and supernatant. L10 and L12.4 cells, which are
      allospecific CD4+ T lymphocytes from the AS rat, were stimulated in the MLR by
      antigen-presenting cells from the August rat, a different strain. We labelled L10
      or L12.4 lymphocytes on day 0, the first day of the stimulation cycle, and
      continued to culture the lymphocytes in vitro. The proliferation of the cells was
      estimated according to their increase in number. The distribution of 111In
      between cell and supernatant fractions and between viable and dead (but intact)
      cells was measured in the cell suspension each day after labelling. The metabolic
      activity of 111In-labelled lymphocytes was compared with control cells by
      measuring their uptake of fluorine-18 fluorodeoxyglucose ([18F]FDG). 111In
      labelled lymphocytes showed a poor proliferative response compared with control
      cells 24-48 h after labelling but increased in number after this time. From 24 to
      72 h, about 70% of 111In was in the supernatant but only about 5%-10% was
      associated with intact dead cells. These dead cells tended to retain their 111In,
      losing less than 30% per day, suggesting that 111In in the supernatant was the
      result of active elimination from viable cells. Moreover, 24 h after culture,
      considerably more 111In was associated with viable than with dead lymphocytes,
      although over the next few days this distribution reversed. 111In-labelled
      lymphocytes took up more [18F]FDG than control cells at 24 h but not at 0 or 72
      96 h; the maximum [18F]FDG uptake coincided with the greatest reduction in cell
      number. Furthermore, [18F]FDG uptake correlated with the initial 111In burden in
      lymphocytes labelled with 111In 24 h previously. The results are consistent with
      active elimination of 111In by 111In-labelled lymphocytes. The energy
      requirements for this are diverted away from cell division, thereby increasing
      the probability of cell death. As lymphocytes become 111In deplete, they recover
      their capacity to proliferate and their risk of death decreases. These findings
      have important implications for 111In-labelled lymphocyte scintigraphy,
      suggesting that cells remaining viable immediately after labelling will either
      subsequently die or alternatively eliminate the label.

PMID- 9142729
TI  - Comparison of three different methods for radiolabelling human activated T
      lymphocytes.
AB  - One approach in the treatment of ovarian cancer patients involves the infusion of
      autologous T lymphocytes coupled with a bispecific monoclonal antibody MOv18/anti
      CD3 (biMAb OC/TR), which recognizes a 38-kDa glycoprotein expressed on ovarian
      carcinomas and the CD3 T cell receptor. However, little is known about the in
      vivo biodistribution of injected activated lymphocytes, information that could be
      obtained by scintigraphic imaging of radiolabelled T cells in order to visualize
      the migratory pattern. We compared the efficiency, stability and toxicity of
      technetium-99m hexamethylpropylene amine oxime (HMPAO), indium-111 oxine and
      fluorine-18 2-fluoro-2-deoxy-d-glucose (FDG) in radiolabelling activated
      lymphocytes targeted with biMAb OC/TR. The mean labelling efficiencies of 111In
      oxine and 18F-FDG using 2.5x10(8) lymphocytes (68% and 64%, respectively) were
      more than twice that of 99mTc-HMPAO (31%). Retention of the radionuclide in the
      cell was highest in the case of 111In-oxine labelling (less than 25% of the
      initial cell-bound activity released after 240 min, as compared with 44% of the
      99mTc label in the same period and 45% of 18F radionuclide released after 150
      min). None of the three radiolabelling reagents induced any significant
      alteration in cell viability or immunophenotype. However, both 111In-oxine and
      18F-FDG induced a loss of cytotoxic activity of lymphocytes against the ovarian
      carcinoma cell line IGROV1, and all three radiolabelling reagents caused a
      significant reduction in the proliferative ability of labelled lymphocytes
      compared to controls, with cell death occurring after 8-9 days. Radiolabelling
      with the more stable 111In-oxine reagent using a higher number of lymphocytes
      (1.4x10(9)) but the same total activity (around 55.5 MBq) resulted in improved
      labelled T cell viability and proliferative ability, although the mean labelling
      efficiency decreased (35.8%). Together the data suggest that 111In-oxine at low
      activity per cell is the most appropriate reagent for radiolabelling activated
      retargeted T lymphocytes useful for in vivo biodistribution studies.

PMID- 9142730
TI  - Flow characteristics of soft-tissue vascular anomalies evaluated by direct
      puncture scintigraphy.
AB  - Soft-tissue vascular anomalies such as haemangioma and vascular malformation are
      treated by surgical resection, arterial embolization or sclerotherapy. Because
      the effect of sclerotherapy, i.e. the percutaneous injection of sclerosing
      agents, depends on intralesional haemodynamics, estimation of flow
      characteristics of soft-tissue vascular anomalies is essential when determining
      appropriate patient management. However, lesions are at present divided into only
      two groups: high flow and low flow. We have developed a new method, direct
      puncture scintigraphy, to evaluate in detail the haemodynamics of vascular
      anomalies under conditions simulating sclerotherapy. Twenty-six soft-tissue
      vascular anomalies in 21 patients were studied. After 30 MBq of technetium-99m Sn
      colloid was injected percutaneously into the intravascular space of the lesion,
      dynamic imaging was performed for 5 min. A time-activity curve for the lesion was
      generated, with the infiltrated activity on injection subtracted. A
      monoexponential curve was fitted to the declining phase of the time-activity
      curve, and mean vascular transit time (MTT) was obtained. The lesions were
      classified into high-flow and low-flow lesions based on radionuclide angiography
      with intravenous injection of 99mTc-labelled red blood cells, and estimates of
      MTT in the two groups were compared. The imaging procedures were carried out with
      no major complications, and broad intralesional diffusion of 99mTc-Sn colloid was
      achieved in most lesions. The high-flow lesions (six lesions) had a short MTT,
      ranging from 1.6 to 3.4 s, while the low-flow lesions (20 lesions) had a longer
      MTT, with no overlap between the groups. MTT showed a wide range in low-flow
      lesions: it was less than 30 s in six lesions and more than 10 min in five other
      lesions. Direct puncture scintigraphy provides a quantitative indicator of the
      flow characteristics of soft-tissue vascular anomalies, and may aid in
      determining treatment strategies for patients with vascular anomalies.

PMID- 9142731
TI  - Use of 99mTc-MIBI scintigraphy in the evaluation of the response of osteosarcoma
      to chemotherapy.
AB  - The use of gamma camera scintigraphy with technetium-99m hexakis-2
      methoxyisobutylisonitrile (99mTc-MIBI) for assessment of the response of high
      grade osteosarcoma to preoperative chemotherapy was evaluated. Twelve patients
      with osteosarcoma of the extremities underwent planar examination with 99mTc-MIBI
      before and after preoperative chemotherapy according to the recommendations of
      the Scandinavian Sarcoma Group. After calculating a quotient for the tumour and
      the average activity of both extremities and correcting for background activity,
      the change in uptake between the two examinations was assessed. This was compared
      with histological examination of the ultimately resected specimen in 11 patients
      and progressive clinical disease in one. All the 11 tumours undergoing
      histological examination showed cellular necrosis of between 50% and 100% as well
      as a reduced uptake of 99mTc-MIBI, while the single progressive tumour showed an
      increased uptake. There was a correlation between the reduction of
      radiopharmaceutical uptake and the histological response in the entire series,
      while the variation was too large to allow conclusions in individual patients.
      This variation may have biological reasons or may be due to the planar imaging
      technique, which only allows semiquantitative evaluation. The technique reflects
      response to therapy but is not yet clinically applicable for the identification
      of poor responders, which would serve as a basis for alteration of the
      chemotherapy regimen. In order to evaluate whether such a role could be
      fulfilled, further studies using single-photon emission tomography with
      correction for attenuation and scattering of photons are necessary.

PMID- 9142732
TI  - Comparison between 360 degrees and 180 degrees data sampling in thallium-201 rest
      redistribution single-photon emission tomography to predict functional recovery
      after revascularization.
AB  - Whether 360 degrees or 180 degrees imaging should be used in cardiac thallium-201
      single-photon emission tomography (SPET) studies to detect coronary artery
      disease remains controversial. Moreover, the relative diagnostic accuracy of 360
      degrees and 180 degrees 201Tl SPET for the assessment of myocardial viability has
      never previously been studied. The aim of this study was to perform a direct
      comparison between 180 degrees and 360 degrees data sampling to detect viable
      myocardium in patients undergoing revascularization; in order to allow optimal
      detection of viability a rest-redistribution protocol was used. The 201Tl results
      were compared with improvement of regional wall motion abnormalities after the
      revascularization, which was considered as the "gold standard" for myocardial
      viability. Thirty-two patients, scheduled for revascularization, underwent rest
      redistribution 201Tl SPET, using a 360 degrees arc. Raw data along a 180 degrees
      arc (45 degrees RAO to LPO) were selected from the original 360 degrees data sets
      (both early an late 201Tl images). All SPET data were analysed semiquantitatively
      using circumferential profiles of the short-axis images; the data were displayed
      in polar maps. Criteria for viability included percentage 201Tl redistribution
      and percentage 201Tl activity on the late image. Regional wall motion was
      assessed with two-dimensional echocardiography before and 3 months after
      revascularization. The sensitivities of 360 degrees and 180 degrees imaging for
      the prediction of functional recovery were 82% and 89%, respectively, whereas the
      specificities were 51% and 55%, respectively. The diagnostic accuracy of 360
      degrees imaging was 62% and that of 180 degrees imaging 67%. This study shows
      that 360 degrees and 180 degrees imaging have comparable diagnostic accuracy in
      the prediction of functional recovery after revascularization. With the newer
      dual-head gamma camera systems with each detector opposing each other, 360
      degrees imaging may be preferred.

PMID- 9142733
TI  - Use of iodine-123 metaiodobenzylguanidine myocardial imaging to predict the
      effectiveness of beta-blocker therapy in patients with dilated cardiomyopathy.
AB  - It is crucial to predict drug effectiveness in chronic disease, such as dilated
      cardiomyopathy (DCM), in which the left ventricular (LV) function might be
      improved by beta-blocker therapy. As the functional improvement effected by beta
      blocker therapy takes more than 2 months, we investigated whether iodine-123
      metaiodobenzylguanidine (123I-MIBG) imaging could be used to predict drug
      effectiveness. We studied 13 patients (11 men and two women; mean age, 43+/-13
      years) with DCM and seven normal subjects (six men and one woman; mean age, 48+/
      16 years). We obtained myocardial single-photon emission tomography (SPET) images
      15 min and 4 h after administration of 123I-MIBG (111 MBq). Studies were
      performed in the patients with DCM before and 1 and 3 months after the
      administration of metoprolol and in the normal subjects. We calculated the
      regional 123I-MIBG washout rate (r-WR) in the SPET image, and the global 123I
      MIBG washout rate (g-WR) and heart-mediastinum activity ratio (H/M) using the
      anterior planar image. We classified patients into those showing a >/=5% increase
      in LV ejection fraction (LVEF) at 3 months compared with LVEF values before the
      treatment (group I, n=7) and those showing a <5% increase in LVEF (group II,
      n=6). In group I, the r-WR values at pretreatment and at 1 month and 3 months of
      treatment, respectively, were 36%+/-19%, 29%+/-14%* and 25%+/-13%* in the
      anterior segment, 39%+/-17%, 33%+/- 17%** and 28%+/-17%* in the lateral segment,
      36%+/- 16%, 31%+/-14%* and 22%+/-12%** in the septal segment and 40%+/-11%, 37%+/
      19% and 31%+/-18%* in the inferior segment; the g-WR was 45%+/-11%, 43%+/-10% and
      34%+/-9%*, respectively (* P<0.05, ** P<0.01 vs pretreatment). In group II, there
      were no significant changes in regional or global parameters during the 3-month
      period. In normal subjects, the r-WR values in each of the anterior, lateral,
      septal and inferior segments were significantly lower than those in groups I and
      II. These values were 18%+/-9%, 18%+/-15%, 20%+/-12% and 21%+/-15%, respectively.
      This study demonstrated that with regional assessment 123I-MIBG SPET imaging can
      be used to predict the functional improvement of LVEF at 1 month of beta-blocker
      therapy in patients with DCM.

PMID- 9142735
TI  - Effect of adrenergic receptor ligands on metaiodobenzylguanidine uptake and
      storage in neuroblastoma cells.
AB  - The effects of adrenergic receptor ligands on uptake and storage of the
      radiopharmaceutical [125I]metaiodobenzylguanidine (MIBG) were studied in the
      human neuroblastoma cell line SK-N-SH. For uptake studies, cells were incubated
      for 15 min with varying concentrations of alpha-agonist (clonidine, methoxamine,
      and xylazine), alpha-antagonist (phentolamine, tolazoline, phenoxybenzamine,
      yohimbine, and prazosin), beta-antagonist (propranolol, atenolol), beta-agonist
      (isoprenaline and salbutamol), mixed alpha/beta antagonist (labetalol), or the
      neuronal blocking agent guanethidine, prior to the addition of [125I]MIBG (0.1
      microM). The incubation was continued for 2 h and specific cell-associated
      radioactivity was measured. For the storage studies, cells were incubated with
      [125I]MIBG for 2 h, followed by replacement with fresh medium with or without
      drug (MIBG, clonidine, or yohimbine). Cell-associated radioactivity was measured
      at various times over the next 20 h. Propanolol reduced [125I]MIBG uptake by
      approximately 30% (P<0.01) at all concentrations tested, most likely due to
      nonspecific membrane changes. However, incubation with the other beta-agonists or
      antagonists failed to elicit significant reductions in uptake. In contrast, all
      of the alpha-agonists significantly inhibited uptake (P<0.05); guanethidine
      >xylazine >clonidine=methoxamine. The alpha-antagonists demonstrated a broad
      range of inhibition (phenoxybenzamine >>phentolamine >prazosin
      >>yohimbine=tolazoline)(P< 0.05). The mixed ligand, labetolol, inhibited MIBG
      uptake in a dose-dependent manner with an apparent IC50 of 0.65 microM. The
      retention studies demonstrated that unlabeled MIBG caused profound self
      inhibition (P<0.01). Clonidine produced a modest inhibition of retention and
      yohimbine had no effect. Labetalol, phenoxybenzamine, guanethidine, and
      propranolol reduced uptake of [125I]MIBG by neuroblastoma cells in culture.
      Although only labetalol has been reported to cause false-negative MIBG scans, our
      results suggest that these other drugs have the potential to interfere with MIBG
      imaging and therapy, particularly at high doses. Adrenergic drugs did not alter
      cytoplasmic retention of [125I]MIBG in neuroblastoma cells but may have potential
      in tumors such as phenochromocytoma, where granular storage of MIBG has been
      observed. Inhibition of [125I]MIBG retention by unlabeled MIBG supports the use
      of high specific activity radioiodinated MIBG for both diagnosis and therapy.

PMID- 9142734
TI  - Coronary vasomotion in patients with syndrome X: evaluation with positron
      emission tomography and parametric myocardial perfusion imaging.
AB  - The aim of this study was to elucidate further the causative mechanism of
      abnormal coronary vasomotion in patients with syndrome X. In patients with
      syndrome X, defined as angina pectoris and documented myocardial ischaemia during
      stress testing with normal findings at coronary angiography, abnormal coronary
      vasomotion of either the micro- or the macrocirculation has been suggested as the
      causative mechanism. Accordingly, we evaluated endothelial function, vasodilator
      reserve, and perfusion heterogeneity in these patients. Twenty-five patients with
      syndrome X (definitely normal coronary arteriogram, group A), 15 patients with
      minimal coronary artery disease (group B) and 21 healthy volunteers underwent
      [13N]ammonia positron emission tomography at rest, during cold pressor
      stimulation (endothelial function) and during dipyridamole stress testing
      (vasodilator reserve). Heterogeneity of myocardial perfusion was analysed by
      parametric polar mapping using a 480-segment model. In both patient groups,
      resting perfusion was increased compared to the normal subjects: group A, 127+/
      31 ml.min-1.100 g-1; group B, 124+/-30 ml.min-1.100 g-1 normal subjects, 105+/-21
      ml.min-1.100 g-1 (groups A and B vs normals, P<0.05). These differences were
      abolished after correction for rate-pressure product. During cold pressor
      stimulation, the perfusion responses (ratio of cold pressor perfusion to resting
      perfusion) were similar among the patients and the control subjects (group A,
      1.20+/-0.23; group B, 1.24+/-0.22; normal subjects, 1.23+/-0.14). Likewise,
      during dipyridamole stress testing, perfusion responses were similar among the
      three groups (group A, 2.71+/-0.67; group B, 2.77+/-1.29; normal subjects, 2.
      91+/-1.04). In group A the heterogeneity of resting perfusion, expressed as
      coefficient of variation, was significantly different from the volunteers (20.1+/
      4.5 vs 17.0+/-3.0, P<0.05). In group B (coefficient of variation 19.4+/-3.9) the
      difference from normal volunteers was not significant. In this study, patients
      with syndrome X and patients with minimal coronary artery disease showed normal
      perfusion responses during cold pressor stimulation and dipyridamole stress
      testing. Our findings therefore suggest that endothelial dysfunction and impaired
      vasodilator reserve are of no major pathophysiological relevance in patients with
      syndrome X. Rather, other mechanisms such as increased sympathetic tone and focal
      release of vasoactive substances may play a role in the pathogenesis of syndrome
      X.

PMID- 9142736
TI  - Renal excretion of iodine-131 labelled meta-iodobenzylguanidine and metabolites
      after therapeutic doses in patients suffering from different neural crest-derived
      tumours.
AB  - Iodine-131 labelled meta-iodobenzylguanidine ([131I]MIBG) is used for diagnostic
      scintigraphy and radionuclide therapy of neural crest-derived tumours. After
      administration of therapeutic doses of [131I]MIBG (3.1-7.5 GBq) to 17 patients
      (n=32 courses), aged 2-73 years, 56%+/-10%, 73%+/-11%, 80%+/-10% and 83%+/-10% of
      the dose was cumulatively excreted as total radioactivity in urine at t=24 h, 48
      h, 72 h and 96 h, respectively. Except for two adult patients, who showed
      excretion of 14%-18% of [131I]meta-iodohippuric acid ([131I]MIHA), the
      cumulatively excreted radioactivity consisted of >85% [131I]MIBG, with 6% of the
      dose excreted as free [131I]iodide, 4% as [131I]MIHA and 2.5% as an unknown
      iodine-131 labelled metabolite. Cumulative renal excretion rates of total
      radioactivity and of [131I]MIBG appeared to be higher in neuroblastoma and
      phaeochromocytoma patients than in carcinoid patients. Based on the excretion of
      small amounts of [131I]meta-iodobenzoic acid in two patients, a possible
      metabolic pathway for [131I]MIBG is suggested. The degree of metabolism was not
      related to the extent of liver uptake of radioactivity.

PMID- 9142737
TI  - Clinical evaluation of technetium-99m infecton for the localisation of bacterial
      infection.
AB  - The aim of the study was to distinguish infection from inflammation in patients
      with suspected infection using technetium-99m Infecton. Ninety-nine patients (102
      studies) referred for infection evaluation underwent imaging with 400 MBq 99mTc
      Infecton at 1 and 4 h. Most patients had appropriate microbiological tests and
      about half (56) had radiolabelled white cell scans as well. No adverse effects
      were noted in any patient. The clinical efficacy of 99mTc-Infecton depended in
      part on whether imaging was undertaken during antibiotic therapy for infection or
      not. In consultation with the microbiologist, 5-14 days of appropriate and
      successful antibiotic therapy was considered adequate to classify some results as
      true-negatives. The figures for sensitivity and specificity of 99mTc-Infecton for
      active or unsuccessfully treated infection were 83% and 91% respectively. It is
      concluded that 99mTc-Infecton imaging contributed to the differential diagnosis
      of inflammation. It is being used as the first imaging modality when bacterial
      infection is suspected.

PMID- 9142738
TI  - The true clinical significance of renography in nephro-urology.
AB  - Isotopic renography is a non-invasive technique used routinely by the clinician
      to provide information about kidney structure and function. Whilst there is no
      doubt of its value in the accurate measurement of glomerular filtration rate and
      in the detection of parenchymal abnormalities, its role in the diagnosis of
      renovascular disease (especially in patients with renal insufficiency), the
      exclusion of obstruction and the evaluation of the patient with either acute
      renal failure or renal transplant dysfunction remains unproven. In part, this
      reflects a failure to standardise protocols and rigorously evaluate diagnostic
      techniques. Recent developments in ultrasound, computerised X-ray tomography and
      nuclear magnetic resonance now present the clinician with rival techniques and
      emphasise the need for the clinical development of isotopic renography.

PMID- 9142739
TI  - Genome sizes of Desulfovibrio desulfuricans, Desulfovibrio vulgaris, and
      Desulfobulbus propionicus estimated by pulsed-field gel electrophoresis of
      linearized chromosomal DNA.
AB  - Pulsed-field gel electrophoresis (PFGE) of linearized, full-length chromosomal
      DNA was used to estimate the genome sizes of three species of sulfate-reducing
      bacteria. Genome sizes of Desulfovibrio desulfuricans, Desulfovibrio vulgaris,
      and Desulfobulbus propionicus were estimated to be 3.1, 3.6, and 3.7 Mb,
      respectively. These values are double the genome sizes previously determined for
      two Desulfovibrio species by two-dimensional agarose gel electrophoresis of DNA
      cut with restriction enzymes. PFGE of full-length chromosomal DNA could provide a
      generally applicable method to rapidly determine bacterial genome size and
      organization.

PMID- 9142741
TI  - Distribution of the insertion element IS240 among Bacillus thuringiensis strains.
AB  - The presence of IS240 was investigated in 69 Bacillus thuringiensis (Bt) strains
      including strains from serotype H1 to H45 and additional strains with known
      Dipteran larvae toxicity. Restriction digests of total DNA and PCR products
      obtained with a single 16-bases primer corresponding to the IS240 inverted
      repeated sequence were hybridized with the IS240A element. The results indicate
      that 67% of the Bt strains tested, including all known mosquitocidal strains,
      possess at least one IS240-related element. PCR experiments indicate that IS240
      represents a family of insertion sequences with several variants.

PMID- 9142740
TI  - The osmotic-1 locus of Neurospora crassa encodes a putative histidine kinase
      similar to osmosensors of bacteria and yeast.
AB  - Osmotically sensitive mutants of Neurospora crassa are unable to grow on medium
      supplemented with 4% NaCl, have altered morphologies and cell-wall compositions,
      and are resistant to dicarboximide fungicides. Osmotic-1 (os-1) mutants have a
      unique characteristic of forming protoplasts that grow and divide in specialized
      liquid medium, suggesting that the os-1+ gene product is important for cell-wall
      assembly. A cosmid containing the os-1+ locus of N. crassa, isolated from a
      genomic cosmid library by chromosomal walk from a closely linked gene, was used
      to subclone the os-1+ gene by functional complementation of an os-1 mutant.
      Analysis of the sequence of complementing DNA predicts that os-1+ encodes a
      predicted protein similar to sensor-histidine kinases of bacteria and a yeast
      osmosensor-histidine kinase. Importantly, the predicted os-1+ protein is
      identical to the N. crassa nik-1 predicted protein that was identified by using
      polymerase chain reaction primers directed against histidine kinase consensus DNA
      sequences. Our results indicate that nik-1 and os-1 encode the same osmosensing
      histidine kinase that plays an important role in the regulation of cell-wall
      assembly and, probably, other cell responses to changes in external osmolarity.

PMID- 9142742
TI  - Isolation and characterization of autolysin-defective mutants of Staphylococcus
      aureus that form cell packets.
AB  - Staphylococcus aureus produces multiple bacteriolytic enzymes (autolysins) and
      grows usually as a mixture of single cells, pairs, short chains, and irregular
      clusters. Autolysin-defective mutants that form cubic cell packets (Pa4A and
      PaH13) or grape-like clusters (Cu9S and CuD10) were isolated from S. aureus FDA
      209P after mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. The Pa4A mutant
      grown in nutrient broth formed cell packets consisting of 8-64 cells that
      appeared regularly arranged in three dimensions. Thin-section electron
      micrographs revealed that the packet cells were encased in an orderly manner
      within a thick peripheral wall and that their septa failed to split. Zymographic
      analysis of enzyme extracts from mutant Pa4A showed that it lacked the 33-kDa
      autolytic enzyme band present in the parent strain. Another mutant, Cu9S, formed
      grape-like clusters and showed a single autolytic enzyme band (33-kDa). The
      possibility that the 33-kDa autolytic enzyme is involved in splitting of the
      septum prior to cell separation inS. aureus is discussed.

PMID- 9142743
TI  - Cloning of an outer membrane protein gene from Campylobacter jejuni.
AB  - An antigen in the outer membrane protein (OMP) fraction of Campylobacter jejuni
      was identified and characterized. Western blot analysis demonstrated antigenic
      differences in this protein between two congenic C. jejuni strains. Strain A74/C,
      which colonizes chickens, expressed the antigen at 34 kDa, while strain A74/O,
      which poorly colonizes chickens, expressed the antigen at 32 and 34 kDa. A
      genomic library was constructed in lambdagt11 with DNA from A74/O and screened
      with antibody raised against C. jejuni OMPs. A clone that possessed a 1.3-kb
      insert and expressed an immunoreactive protein fused to beta-galactosidase was
      isolated and purified. DNA sequence analysis revealed the insert contained one
      open reading frame 864 bases long. The deduced amino acid sequence demonstrated
      56.3% similarity with Bacillus steorothermophilus glnH, a glutamine-binding
      protein, and 54.0% similarity with C. jejuni PEB1, a putative colonization
      adhesin. Southern hybridization, Northern hybridization, and DNA sequence
      analyses of the congenic colonizing and noncolonizing strains of C. jejuni failed
      to distinguish the two strains and revealed only one copy of the gene. Post
      translational modification may be an alternate explanation for the antigenic
      differences seen between the two strains.

PMID- 9142744
TI  - Cloning, sequence, and expression of the L-(+) lactate dehydrogenase of
      Streptococcus bovis.
AB  - The ldh gene encoding the fructose-1,6-diphosphate-dependent L-(+) lactate
      dehydrogenase from the ruminal bacterium Streptococcus bovis was cloned and
      sequenced. A genomic library of S. bovis JB1 DNA was constructed in lambda ZAP II
      and screened by use of a heterologous probe derived from the cloned Streptococcus
      mutans ldh gene. Several clones were isolated that contained a common 2.9-kb
      fragment as determined by restriction analysis. Nucleotide sequence analysis
      revealed a 987-bp open reading frame with extensive homology to Streptococcus
      thermophilus and S. mutans ldh nucleic acid and amino acid sequences. Expression
      of the cloned S. bovis ldh gene in Escherichia coli was confirmed by the ability
      to complement the ldh mutation of E. coli FMJ39, by using an in-gel activity
      screen and by enzymatic assay. Increased LDH activity was observed in S. bovis
      JB1 containing the cloned ldh genes on a multicopy plasmid.

PMID- 9142745
TI  - Purification and properties of alcohol oxidase from Candida methanosorbosa M
      2003.
AB  - Alcohol oxidase from Candida methanosorbosa was purified about sixfold with a
      yield of 37.6% from the culture broth of Candida methanosorbosa M-2003. The
      enzyme preparation was homogeneous on slab gel electrophoresis. The purified
      enzyme had an optimal pH from 6.0 to 9.0 and was stable in the range 6.0-8.5. Its
      optimal temperature of reaction was 50 degrees C, and it was stable below 50
      degrees C. In the presence of NaN3, the enzyme retained its initial activity at
      30 degrees C for 35 days, indicating stability for a long term, so far. The
      isoelectric point was pH 4.3. Its molecular weight was 620, 000 by gel filtration
      chromatography and 80,000 by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. These results indicate that the enzyme consists of 8 subunits.

PMID- 9142746
TI  - Plasmid-encoded sequestration of copper by Pseudomonas pickettii strain US321.
AB  - Pseudomonas pickettii strain US321 appeared to elicit a copper resistance
      mechanism upon exposure to copper. The bacterial colonies turned blue in the
      presence of this metal in a chemically defined medium, suggesting accumulation of
      copper. Prolonged exposure to copper resulted in the characteristic "copper sink"
      morphology of the colonies. Atomic absorption spectrophotometric analysis
      confirmed that this organism can accumulate copper. The strain US321 exhibited a
      high-molecular-weight plasmid, pUS321. The plasmid-cured strain, PC25, is highly
      sensitive to copper owing to a poor copper management. A plasmid-encoded
      sequestration mechanism operating in the strain US321 is suggested.

PMID- 9142747
TI  - Correlation of resistance to the alkaloid lycorine with the degree of
      suppressiveness in petite mutants of Saccharomyces cerevisiae.
AB  - In previous papers (Del Giudice et al. Curr Genet 8:493-497, 1984; Massardo et
      al. Curr Genet 17:455-457, 1985) we have shown that strains of Saccharomyces
      cerevisiae that are devoid of mitochondrial DNA (rhoo) are resistant to the
      alkaloid lycorine isolated from Amaryllis plants, whereas strains containing
      mitochondrial DNA (rho-, mit-, or rho+) are sensitive to this drug. In addition,
      we were able to show that the so-called hypersuppressive petites, whose
      mitochondrial genomes consist of short regions of DNA containing an ori
      sequence,show intermediate resistance. In this paper, we demonstrate that the
      degree of suppressiveness of a rho- mutant correlates with the degree of
      resistance to lycorine.

PMID- 9142748
TI  - Competitive brain activity in visual attention.
AB  - Visual attention can be considered from the perspective of distributed brain
      activity engendered by visual input. We propose that visual objects compete for
      representation in multiple brain systems, sensory and motor, cortical and
      subcortical. Competition is integrated, however, such that multiple systems
      converge, working on the different properties and action implications of a
      selected object. Top-down priming biases competition towards objects relevant to
      current behaviour. Recent single-unit studies have shown widespread suppression
      of ignored-object representations in extrastriate cortex, and patterns of spatial
      and nonspatial priming by task relevance. Human and monkey lesion studies have
      demonstrated the strong integration tendency of different spatial and nonspatial
      systems, also revealed in recent studies of normal behaviour. In many cases, no
      unitary brain system may be responsible for unitary cognitive events such as
      attention. Such events may emerge as distinct systems converge to work on common
      cognitive problems.

PMID- 9142749
TI  - Genetic analyses of emotionality.
AB  - Quantitative genetic research on emotionality in animals and humans consistently
      points to genetic influence. Molecular genetic research is beginning to identify
      quantitative trait loci that are associated with the genetically related
      emotional domains of neuroticism, anxiety and depression.

PMID- 9142750
TI  - Hippocampal lesions and path integration.
AB  - Research on spatial problem-solving over the past two years has linked the
      hippocampus to path integration, that is, the use of movement-related cues to
      guide spatial behavior. Path integration may underlie the forms of place learning
      that are impaired by hippocampal damage. It remains a challenge to determine
      whether path integration is the central function of the hippocampus or but one of
      many.

PMID- 9142751
TI  - LTP, NMDA, genes and learning.
AB  - In the past year, several tests of the hypothesis that NMDA-dependent hippocampal
      long-term potentiation (LTP) underlies learning have been reported. Data from
      mutant mice point to a potential role for NMDA-dependent LTP in hippocampal place
      cell function and spatial learning, but evidence for a causal relation is not yet
      available. Other studies have shown that robust spatial learning is possible
      without NMDA-dependent hippocampal LTP. Although the current evidence for the
      role of LTP in learning is mixed, LTP remains the most promising neural mechanism
      for associative learning. Several new experimental approaches are now available
      for future research.

PMID- 9142752
TI  - Memory consolidation, retrograde amnesia and the hippocampal complex.
AB  - Results from recent studies of retrograde amnesia following damage to the
      hippocampal complex of human and non-human subjects have shown that retrograde
      amnesia is extensive and can encompass much of a subject's lifetime; the degree
      of loss may depend upon the type of memory assessed. These and other findings
      suggest that the hippocampal formation and related structures are involved in
      certain forms of memory (e.g. autobiographical episodic and spatial memory) for
      as long as they exist and contribute to the transformation and stabilization of
      other forms of memory stored elsewhere in the brain.

PMID- 9142753
TI  - Memory beyond the hippocampus.
AB  - Improved neuroanatomical knowledge, technical and methodological innovations
      (such as PET), and more refined conceptualizations of memory have inspired a
      reappraisal of theoretical beliefs regarding the role of the hippocampus in
      memory. In the past few years, it has become apparent that the influence of the
      medial temporal lobe regions extends beyond memory and that memory processes
      (such as encoding, consolidation and retrieval) involve not only the hippocampus
      and the medial temporal and diencephalic regions, but also widely distributed
      neocortical and perhaps even cerebellar regions.

PMID- 9142755
TI  - Neural basis of utility estimation.
AB  - The allocation of behavior among competing activities and goal objects depends on
      the payoffs they provide. Payoff is evaluated among multiple dimensions,
      including intensity, rate, delay, and kind. Recent findings suggest that by
      triggering a stream of action potentials in myelinated, medial forebrain bundle
      axons, rewarding electrical brain stimulation delivers a meaningful intensity
      signal to the process that computes payoff.

PMID- 9142754
TI  - Dopamine neurons and their role in reward mechanisms.
AB  - Information related to rewards is processed by a limited number of brain
      structures. Recent studies have demonstrated that dopamine neurons respond to
      appetitive events, such as primary rewards and reward-predicting stimuli. Rather
      than responding unconditionally, these neurons signal deviations from the
      prediction of future appetitive events. These reward-related responses correspond
      formally to concepts of behavioral and computational learning theories and may
      thus constitute teaching signals for appetitive learning.

PMID- 9142757
TI  - The neural system of language: structure and development.
AB  - Recent neuroimaging and neuropsychological research in adults and infants
      suggests that the neural system for language is widely distributed and shares
      organizational principles with other cognitive systems in the brain.
      Connectionist modelling has clarified that networks operating with associative
      mechanisms can display properties typically associated with genetically
      predetermined and dedicated symbolic functions.

PMID- 9142756
TI  - Serotonin receptors in cognitive behaviors.
AB  - The serotonergic system appears to play a role in behaviors that involve a high
      cognitive demand and in memory improvement or recovery from impaired cognitive
      performance, as made evident after administration of serotonin 5-HT2A/5-HT2C or 5
      HT4 receptor agonists or 5-HT1A or 5-HT3 receptor antagonists. These serotonin
      receptor subtypes are localized on 'cognitive' pathways, with the hippocampus and
      frontal cortex as the main target structures. A better understanding of the role
      played by these and other serotonin receptor subtypes in cognition is likely to
      result from the recent availability of new specific ligands and new molecular
      tools, such as gene knock-out and transgenic mice.

PMID- 9142758
TI  - Sensory and cognitive functions of the basal ganglia.
AB  - Recent studies have found that the basal ganglia are involved in diverse
      behavioral activities and suggest that they have executive functions. Highlights
      from the past year include anatomical and clinical studies that have used
      sophisticated, novel methods to confirm a role for the basal ganglia in
      somatosensory discrimination, visual perception, spatial working memory and habit
      learning.

PMID- 9142759
TI  - Network models of the basal ganglia.
AB  - Over the past year, a number of conceptual and mathematical models of the basal
      ganglia and their interactions with other areas of the brain have appeared in the
      literature. Even though the models each differ in significant ways, several
      computational principles, such as convergence, recurrence and competition, appear
      to have emerged as common themes of information processing in the basal ganglia.
      Simulation studies of these models have provoked new types of questions at the
      many levels of inquiry linking biophysics to behavior.

PMID- 9142760
TI  - Brainstem, cerebellar and limbic neuroanatomical abnormalities in autism.
AB  - Recent autopsy and/or quantitative magnetic resonance imaging studies of autistic
      patients have identified agenesis of the superior olive, dysgenesis of the facial
      nucleus, reduced numbers of Purkinje neurons, hypoplasia of the brainstem and
      posterior cerebellum, and increased neuron-packing density of the medial,
      cortical and central nuclei of the amygdala and the medial septum. As
      neurogenesis occurs for these different neuron types during approximately the
      fifth week of gestation, the possibility is raised that this may be a 'window of
      vulnerability' for autism; the likely etiologic heterogeneity of autism suggests
      that other windows of vulnerability are also possible.

PMID- 9142761
TI  - Mnemonic functions of the basal ganglia.
AB  - A synthesis of older and recent work on mnemonic functions of the basal ganglia
      in rats, monkeys and humans emphasizes a reciprocal relationship of the caudate
      nucleus and putamen with the cerebral cortex, which mediates the memory of
      consistent relationships between stimuli and responses (sometimes called habits)
      that often involve relationships between the individual and its environment
      (egocentric memory). Evidence at several levels of analysis (including
      neuroplastic synaptic changes, activity of single neurons, and behavioral changes
      caused by lesions or neurochemical manipulations) implicate dopamine release from
      nigro-striatal neurons in the reinforcement, or strengthening, of neural
      representations in the basal ganglia.

PMID- 9142762
TI  - Toward a neurobiology of temporal cognition: advances and challenges.
AB  - A rich tradition of normative psychophysics has identified two ubiquitous
      properties of interval timing: the scalar property, a strong form of Weber's law,
      and ratio comparison mechanisms. Finding the neural substrate of these properties
      is a major challenge for neurobiology. Recently, advances have been made in our
      understanding of the brain structures important for timing, especially the basal
      ganglia and the cerebellum. Surgical intervention or diseases of the cerebellum
      generally result in increased variability in temporal processing, whereas both
      clock and memory effects are seen for neurotransmitter interventions, lesions and
      diseases of the basal ganglia. We propose that cerebellar dysfunction may induce
      deregulation of tonic thalamic tuning, which disrupts gating of the mnemonic
      temporal information generated in the basal ganglia through striato-thalamo
      cortical loops.

PMID- 9142763
TI  - Schizophrenia: a disorder of neurodevelopment?
AB  - For the first time, there is a pathogenic hypothesis of schizophrenia based upon
      reasonable empirical data. The hypothesis is that schizophrenia is a disorder
      arising from aberrant brain development. The neurodevelopmental view of
      schizophrenia is supported by neuropathological, epidemiological and clinical
      findings. Here, the evidence in favour of the model is summarized, together with
      a consideration of its weaknesses.

PMID- 9142764
TI  - Cognitive neuroscience.

PMID- 9142765
TI  - Web alert. Cognitive neuroscience.

PMID- 9142766
TI  - Varicella-zoster virus vaccine.

PMID- 9142767
TI  - An approach to the validation of markers for use in AIDS clinical trials.
AB  - Dr. Mildvan and coauthors have thoroughly reviewed and documented what is known
      about the validation of surrogate markers for use in clinical trials. They have
      proposed a classification system based on the usefulness of available immunologic
      and virological assays as measures of prognosis, drug activity, and therapeutic
      efficacy. The latter, a type II marker in the proposed classification, should
      estimate the proportion of treatment effect explained by change in the marker
      induced by therapy and, if complete, can substitute for clinical endpoints. HIV
      clinical trialists have had a long-standing interest in using surrogates for
      clinical endpoints to facilitate conduct of experimental protocols and to
      decrease the time and effort required to develop new treatment strategies. The
      approach outlined in this review by experienced clinicians, biostatisticians, and
      immunologists provides a framework to evaluate currently available and potential
      surrogate markers.

PMID- 9142768
TI  - Introduction. Issues concerning antifungal susceptibility testing.

PMID- 9142769
TI  - Antifungal susceptibility testing: technical advances and potential clinical
      applications.
AB  - The clinical application of in vitro antifungal susceptibility testing has been
      limited by a lack of reproducibility and uncertain clinical relevance. As a
      result of several collaborative studies, the National Committee for Clinical
      Laboratory Standards (NCCLS) has proposed a standardized antifungal
      susceptibility test method, NCCLS M27-T. More convenient, user-friendly methods
      (microdilution broth and stable gradient technology) have been evaluated, and the
      potential for a similar process with a disk diffusion method is apparent.
      Adaptation of the standard method for susceptibility testing of filamentous fungi
      appears promising. The existence of a standardized method facilitates meaningful
      analysis of studies addressing the issue of clinical relevance of antifungal
      susceptibility testing. Correlation of MICs with clinical response to therapy is
      beginning to emerge, most notably in relation to fluconazole and itraconazole
      therapy for oropharyngeal candidiasis associated with infection with the human
      immunodeficiency virus. This accumulated experience with antifungal
      susceptibility testing allows us to provide several specific recommendations for
      antifungal susceptibility testing in the clinical laboratory. Application of this
      developing technology to new antifungal agents and other disease states will
      enhance our ability to effectively deal with the emerging problem of fungal
      infection.

PMID- 9142770
TI  - Mycotic thoracic aneurysm due to Clostridium septicum and occult adenocarcinoma
      of the cecum.

PMID- 9142771
TI  - A meta-analysis of extended-interval dosing versus multiple daily dosing of
      aminoglycosides.
AB  - We conducted a meta-analysis of 22 randomized, controlled trials in which
      extended-interval dosing of aminoglycosides was compared with multiple daily
      dosing. When we classified intermediate outcomes as successes, we found that
      patients receiving extended-interval dosing were at significantly reduced risk of
      clinical treatment failure (risk difference, -3.4%; 95% confidence interval [CI],
      -6.7% to -0.2%; P = .039) and that there was a trend toward reduced risk of
      bacteriologic failure (risk difference, -1.7%; 95% CI, -5.4% to +2.1%; P = .38).
      Reclassification of intermediate outcomes as failures yielded similar results.
      There was significant heterogeneity among the trials, necessitating cautious
      interpretation of these outcomes. There were negligible differences in the risk
      of nephrotoxicity (risk difference, -0.6%; 95% CI, -2.4% to +1.1%; P = .46) and
      ototoxicity (risk difference, +0.3%; 95% CI, -1.2% to +1.8%; P = .71). We
      conclude that for many indications, extended-interval dosing of aminoglycosides
      appears to be as effective as conventional dosing, with similar rates of
      toxicity. The added convenience of extended-interval dosing makes it an
      attractive alternative to conventional dosing.

PMID- 9142772
TI  - A meta-analysis of the relative efficacy and toxicity of single daily dosing
      versus multiple daily dosing of aminoglycosides.
AB  - We performed a meta-analysis of the efficacy and toxicity of single daily dosing
      (SDD) vs. multiple daily dosing of aminoglycosides and summarized the results of
      the four previously published meta-analyses on this subject. Our analysis showed
      that the overall clinical response rate favored SDD therapy (mean difference,
      +3.06%; 95% confidence limit [CL], +0.17% to +5.95%; P = .04). However, we found
      no significant difference in the overall microbiological response rates (mean
      difference, +1.25%; 95% CL, -0.40% to +2.89%) or in the clinical response rates
      (mean difference, +0.62%; 95% CL, -2.48% to +3.71%) when patients who received
      adjunctive antimicrobial therapy were excluded from the analysis. No significant
      differences were found in the incidences of nephrotoxicity, ototoxicity, or
      vestibular toxicity; the summary differences in the rates of these toxicities
      were -0.18% (95% CL, -2.17% to +1.81%), +1.38% (95% CL, -0.99% to +3.75%), and 
      3.05% (95% CL, -10.69% to +4.59%), respectively. These results are similar to
      those of the previously published meta-analyses.

PMID- 9142773
TI  - Single daily dosing of aminoglycosides in immunocompromised adults: a systematic
      review.
AB  - We examined the efficacy and toxicity of single daily dosing (SDD) of
      aminoglycosides for febrile, immunocompromised adults by systematically reviewing
      four randomized, controlled trials of SDD vs. standard dosing regimens. We
      assessed the methodological quality of each study and extracted data pertaining
      to efficacy and toxicity outcomes. Pooled risk ratios for the efficacy outcomes
      were bacteriologic cure, 1.00 (95% confidence interval [CI], 0.86-1.16); clinical
      cure, 0.97 (95% CI, 0.91-1.05); and mortality, 0.93 (95% CI, 0.62-1.41). The
      pooled nephrotoxicity risk ratio was 0.78 (95% CI, 0.31-1.94). Only one study
      assessed ototoxicity. Although our study was limited by the small number of
      trials available for review, the results suggest that SDD of aminoglycosides may
      be efficacious for febrile, immunocompromised patients. Additional studies are
      necessary for more precise quantification of the mortality and toxicity risk
      ratios.

PMID- 9142774
TI  - Meta-analyses are no longer required for determining the efficacy of single daily
      dosing of aminoglycosides.

PMID- 9142775
TI  - Single daily dose of aminoglycosides--a concept whose time has not yet come.

PMID- 9142776
TI  - Surveillance cultures of blood, urine, and throat specimens are not valuable for
      predicting cytomegalovirus disease in liver transplant recipients. Boston Center
      for Liver Transplantation Cytomegalovirus Immune Globulin Study Group.
AB  - The role of markers of cytomegalovirus (CMV) infection, such as the isolation of
      CMV, the presence of CMV antigenemia, or detection of viral DNA by polymerase
      chain reaction (PCR) assay, as predictors of subsequent CMV disease has been
      examined in recent studies. We studied the value of performing surveillance
      cultures of blood, urine, and throat specimens in a cohort of 156 liver
      transplant recipients who had participated in clinical trials and had received
      ganciclovir only for documented CMV disease. Cultures of urine and throat
      specimens for detection of CMV were performed every week, and cultures of blood
      specimens were performed every other week for the first 2 months after
      transplantation, then monthly for 6 months. Eighty-nine (57%) of 156 patients
      developed CMV infection, 41 (46%) of whom developed clinical CMV disease (36 had
      organ involvement and five had CMV syndrome). Fifty (32%) of 156 patients had
      positive blood cultures, 35 (22%) had positive urine cultures, and 41 (26%) had
      positive throat cultures. The positive and negative predictive values of
      surveillance cultures for predicting CMV disease were as follows: blood cultures,
      46% and 83%, respectively; urine cultures, 26% and 74%, respectively; and throat
      cultures, 32% and 76%, respectively. These data indicate that such cultures are
      not useful in predicting CMV disease in liver transplant recipients. Future
      studies should examine the value of alternative markers, such as CMV antigenemia
      or the detection of viral DNA by PCR, for predicting CMV disease in this setting.

PMID- 9142777
TI  - Cytomegalovirus disease occurring before engraftment in marrow transplant
      recipients.
AB  - Little information is available regarding the incidence, clinical course, and
      response to treatment of cytomegalovirus (CMV) disease that occurs before
      engraftment in marrow transplant recipients. We identified 25 patients over a
      12.5 year period who developed CMV disease before achieving engraftment. Twelve
      cases were diagnosed during life, and 13 cases were diagnosed at autopsy. The
      lung was the site most commonly involved (92% of patients), and most of the
      patients (92%) were CMV seropositive. Significant copathogens were identified in
      45% of the patients. All nine patients with CMV pneumonia died within 6 weeks
      after the diagnosis was made, and one of two patients with gastrointestinal
      disease also died 6 weeks after the diagnosis was made despite the administration
      of antiviral therapy. Surveillance cultures were not helpful in identifying
      patients at risk for disease. Histopathological examination of the lungs of
      patients with early CMV pneumonia only infrequently showed typical CMV lesions.
      In conclusion, CMV disease occurring before engraftment in CMV-seropositive
      recipients was uncommon, was frequently associated with the presence of other
      opportunistic pathogens, and was associated with a high fatality rate. Better
      diagnostic methods to identify patients at risk are required in the
      preengraftment period.

PMID- 9142779
TI  - Laboratory monitoring of cytomegalovirus disease--is polymerase chain reaction
      the answer?

PMID- 9142778
TI  - Cytomegalovirus (CMV) viremia and the CD4+ lymphocyte count as predictors of CMV
      disease in patients infected with human immunodeficiency virus.
AB  - We screened 192 patients infected with human immunodeficiency virus (HIV) to
      examine the relation between CD4+ lymphocyte counts and cytomegalovirus (CMV)
      viremia and the occurrence of CMV disease and subsequent duration of survival.
      When we stratified the viremic patients by CD4+ lymphocyte counts, the
      proportions were as follows: <50/mm3, 20 (25%) of 80 patients; 50-100/mm3, 2
      (5.5%) of 36; 101-150/mm3, none of 14; and >150/mm3, 1 (1.5%) of 62. After a mean
      follow-up period of 8.5 months, 21 (11%) of 192 patients developed CMV disease.
      The probability of developing CMV disease at 6 months was 13% when the CD4+
      lymphocyte count was <50/mm3, 3% when the CD4+ lymphocyte count was 50-100/mm3,
      and 0 when the CD4+ lymphocyte count was >100/mm3; this probability was 46% for
      viremic patients and 1% for nonviremic patients. In a multivariate analysis, CMV
      viremia was independently prognostic of CMV disease (relative risk, 22.03; 95%
      confidence interval, 6.49-78.97; P < .001), whereas a CD4+ lymphocyte count of
      <50/mm3 was not (P = .26). These results support the value of CMV viremia for
      predicting which HIV-infected patients are at risk of developing CMV disease and
      should therefore receive primary prophylaxis.

PMID- 9142780
TI  - Immunization of healthy adult subjects in the United States with inactivated
      Mycobacterium vaccae administered in a three-dose series.
AB  - Heat-killed Mycobacterium vaccae vaccine was administered in a three-dose
      intradermal schedule to 10 healthy adult volunteers at 0, 2, and 10 months. Local
      and systemic side effects were monitored and vaccine site reactions were measured
      and photographed at visits 2 days, 14 days, and 2 months after each dose.
      Reactions to skin tests with purified protein derivative (PPD) and Mycobacterium
      avium sensitin (MAS) and titers of antibody to arabinose lipoarabinomannin were
      determined at baseline and after each dose of vaccine. Lymphocyte proliferation
      responses to MAS were determined after the final dose of vaccine. Immunization
      was safe and well tolerated, with maximal induration (range, 6-25 mm) at 2 days.
      PPD skin test conversions did not occur. Seven subjects completed the three-dose
      schedule; preexisting immunologic responses to mycobacteria were boosted in
      three, and a new response was elicited in one. M. vaccae vaccine is safe and
      induces measurable immunologic responses to mycobacterial antigens in some
      healthy adults.

PMID- 9142781
TI  - Early detection of sequela-prone osteomyelitis in children with use of simple
      clinical and laboratory criteria.
AB  - To determine which clinical or laboratory criteria best reflected the prognosis
      for 83 children with acute hematogenous osteomyelitis (AHO), they were compared
      with outcomes after a follow-up of at least 2 months (for 78%, > or = 6 months).
      Twenty-eight children (34%) developed sequelae. They had higher serum C-reactive
      protein (CRP) concentrations (days 1-6 of treatment; P = .0004 to .0001) and
      higher clinical scores (P = .0001) than did patients who had an uneventful
      recovery. The frequency of sequelae increased from 3% to 73% (P = .0001) when CRP
      concentrations exceeded the defined cutoff limits and the clinical scores were >
      or = 1. Age, the duration of symptoms at diagnosis, and the type and duration of
      intravenous antimicrobial therapy or surgical management did not differ (P > .05)
      between children with and without sequelae. Both CRP determinations and clinical
      evaluations with use of a scoring system enable early detection of sequela-prone
      AHO in children and are most accurate when used together.

PMID- 9142783
TI  - Kingella kingae: an emerging cause of invasive infections in young children.
AB  - Kingella kingae, a fastidious hemolytic gram-negative bacillus once considered to
      be an exceptional cause of disease, has emerged in recent years as an important
      invasive pathogen in children. When synovial fluid and other exudates were
      inoculated into blood culture bottles, enhanced recovery of the organism was
      observed, and an annual incidence of invasive K. kingae infections of 27.4 per
      100,000 children younger than age 24 months was demonstrated in southern Israel.
      Skeletal infections are the most common clinical presentation of K. kingae, and
      studies conducted in that region have shown that this organism is the most common
      etiology of septic arthritis in children below the age of 24 months. Other
      invasive diseases caused by K. kingae include bacteremia, endocarditis, and
      infections involving the lower respiratory tract, the eyes, or the central
      nervous system. Recent studies have demonstrated that K. kingae is part of the
      normal oropharyngeal flora of young children. Clinical data suggest that the
      organism may gain access to the bloodstream in the course of an upper respiratory
      infection or stomatitis. The organism is susceptible to a wide range of
      antimicrobial drugs, and with the exception of some cases of endocarditis, K.
      kingae infections in children usually run a benign clinical course.

PMID- 9142782
TI  - A 5-year retrospective review of adverse drug reactions and their risk factors in
      human immunodeficiency virus-infected patients who were receiving intravenous
      pentamidine therapy for Pneumocystis carinii pneumonia.
AB  - The incidence and severity of adverse drug reactions (ADRs) in human
      immunodeficiency virus-infected persons receiving intravenous pentamidine for
      Pneumocystis carinii pneumonia during a 5-year period were reviewed
      retrospectively. Predisposing risk factors for ADRs were identified. ADRs were
      included if they occurred during or within 1 week following the discontinuation
      of pentamidine treatment. Nephrotoxicity, dysglycemia, hepatotoxicity,
      hyperkalemia, and hyperamylasemia accounted for 80% of ADRs (n = 174) that
      occurred in 76 (71.7%) of 106 patients during 84 treatment courses of
      pentamidine. A significant relationship between hypoglycemia and nephrotoxicity
      was observed (P = .002). Four factors were significantly associated with
      occurrence of an ADR: number of concomitant medications (odds ratio [OR] = 1.36,
      P = .005), nonwhite ethnicity (OR = 5.00, P = .017), cumulative dosage of
      pentamidine (OR = 1.03, P = .030), and concurrent use of other nephrotoxic drugs
      (OR = 2.34, P = .047). Two factors, daily dosage and history of intravenous drug
      use, approached significance. Knowledge of and avoidance of potential risk
      factors might allow safer use of pentamidine and reduce the prevalence of ADRs.

PMID- 9142784
TI  - Flavimonas oryzihabitans bacteremia: clinical features and microbiological
      characteristics of isolates.
AB  - Flavimonas oryzihabitans is rarely reported as a pathogen in humans. Twelve cases
      of F. oryzihabitans bacteremia were diagnosed at National Taiwan University
      Hospital over a 3-year period. The clinical features of these patients were
      analyzed, and antimicrobial susceptibilities and random amplified polymorphic DNA
      (RAPD) patterns of the 12 isolates were studied. Among these 12 patients, eight
      (67%) had underlying neoplastic diseases and all acquired F. oryzihabitans
      bacteremia while hospitalized. The clinical syndromes included primary bacteremia
      in 5 patients (42%), biliary tract infection in 3 (25%), and peritonitis,
      subdural empyema, infusion-related bacteremia, and pneumonia in 1 each.
      Polymicrobial bacteremia or concomitant fungemia was seen in three patients
      (25%). All the patients survived after antibiotic treatment. All isolates were
      susceptible to piperacillin, third-generation cephalosporins, aminoglycosides,
      and quinolones but resistant to cephalothin, cefuroxime, and trimethoprim.
      Susceptibility to aztreonam was variable (25%). The RAPD patterns differed among
      the isolates, indicating the epidemiological unrelatedness of these infections.
      F. oryzihabitans should be included as an etiology of severe nosocomial infection
      in patients with underlying debilitating diseases.

PMID- 9142785
TI  - Clindamycin resistance in the Bacteroides fragilis group: association with
      hospital-acquired infections.
AB  - A retrospective study was conducted to assess the relationships between
      clindamycin resistance in members of the Bacteroides fragilis group, previous
      antimicrobial therapy, and the context for the development of infection, whether
      in the community or during hospitalization. Eighty-five clindamycin-resistant
      clinical strains (one isolate per patient) isolated from January 1988 to October
      1994 were matched (one to one) with clindamycin-susceptible isolates recovered
      during the same period, and the charts of the patients from whom the isolates
      were recovered were reviewed retrospectively. Of the clindamycin-resistant
      strains, 65% were recovered from patients with hospital-acquired infections
      compared with 40% of the clindamycin-susceptible strains (odds ratio [OR], 2.75;
      95% confidence interval [CI], 1.41-5.38; P = .002). Prior antimicrobial therapy
      for > or = 48 hours was also associated with clindamycin resistance (OR, 2.33;
      95% CI, 1.16-4.70; P = .02). However, clindamycin resistance remained associated
      with hospital-acquired infections independent of prior antimicrobial therapy
      (Mantel-Haenszel weighted average OR, 2.22; 95% CI, 1.03-4.89; P = .04).
      Clinicians should consider the risks for clindamycin resistance when treating
      hospital-acquired infections caused by members of the B. fragilis group.

PMID- 9142786
TI  - Rapid detection of cytomegalovirus in bronchoalveolar lavage fluid and serum
      samples by polymerase chain reaction: correlation of virus isolation and clinical
      outcome for patients with human immunodeficiency virus infection.
AB  - Bronchoalveolar lavage (BAL) fluids and serum samples from 153 patients with
      pulmonary symptoms who were infected with human immunodeficiency virus (HIV) and
      underwent BAL were examined for the presence of cytomegalovirus (CMV) by
      conventional culture and by polymerase chain reaction (PCR) for detection of CMV
      DNA. PCR detected CMV more frequently than did cultures of BAL fluid (PCR of BAL
      fluid, 53%; PCR of serum, 40%; and culture, 30%). In a multivariate model,
      development of extrapulmonary CMV disease was predicted by the finding of CMV in
      BAL fluid by culture (relative risk [RR], 8.0; confidence interval [CI], 3.8
      16.8) or the finding of CMV DNA in serum (RR, 7.4; CI, 3.2-17.3) or BAL fluid
      (RR, 8.0; CI, 3.1-20.7) by PCR. Mortality was found to be similar for patients
      who did or did not have CMV detected by either culture or PCR. Detection of CMV
      DNA by PCR was a more rapid and sensitive technique than conventional culture.
      Detection of CMV DNA in BAL fluid or serum predicted subsequent development of
      extrapulmonary CMV disease but not death for HIV-infected patients with pulmonary
      symptoms.

PMID- 9142787
TI  - Microbiological cultures of heart valves and valve tags are not valuable for
      patients without infective endocarditis who are undergoing valve replacement.
AB  - We evaluated the significance of the results of microbiological cultures of heart
      valves and identification tags from newly inserted prosthetic valves that were
      removed from patients with valvular heart disease; none of these patients had a
      preoperative diagnosis of endocarditis. We reviewed the charts of patients with
      positive cultures for evidence of infections before or after surgery. Cultures
      were positive for 11.9% of 219 valves (206 native valves and 13 prosthetic or
      bioprosthetic valves) and 11.6% of 224 tags. The most common isolates were
      coagulase-negative staphylococci. Typical agents of endocarditis--viridans
      streptococcus, Enterococcus faecalis, and Staphylococcus aureus--were cultured
      from five specimens, and Mycobacterium avium complex was identified in six
      valves. None of the patients with positive valve or tag cultures developed
      postsurgical endocarditis or wound infection. Findings on histopathologic
      examination of the valves were not consistent with endocarditis. We conclude that
      the results of cultures of valves from patients without preoperative diagnoses of
      endocarditis lack clinical significance, and positive tag cultures are not
      predictive of postsurgical infection. Positive cultures are most likely a result
      of contamination during surgery or thereafter.

PMID- 9142788
TI  - Isolation of various genotypes of Clostridium difficile from patients and the
      environment in an oncology ward.
AB  - The epidemiology of Clostridium difficile-associated diarrhea (CDAD) is not well
      defined in nonepidemic situations because precise biotyping techniques have only
      recently become available. Arbitrarily primed polymerase chain reaction (AP-PCR)
      was used to determine strain identity of C. difficile isolates recovered on our
      oncology ward, at an incidence rate of 0.84%. Twenty-one strains of C. difficile,
      which were grouped into 18 different AP-PCR types, were isolated from patients'
      specimens. Forty-two C. difficile isolates recovered from the environment (33
      toxigenic and 9 nontoxigenic) represented 9 different AP-PCR types. The most
      commonly found type, a toxigenic strain accounting for 29% of the environmental
      isolates, was widespread throughout the ward. None of the environmental types
      were found among the isolates from patients. Three patients' isolates were of the
      same AP-PCR type, and two of these patients had occupied neighboring rooms at the
      same time. The diversity of C. difficile isotypes suggests that endemic
      nosocomial CDAD is not necessarily clonally spread.

PMID- 9142789
TI  - Detection of resistance to isoniazid, rifampin, and streptomycin in clinical
      isolates of Mycobacterium tuberculosis by molecular methods.
AB  - Molecular techniques can detect drug resistance in Mycobacterium tuberculosis,
      but whether these methods are practical for clinical laboratory use and the
      management of tuberculosis is unclear. We evaluated several available molecular
      methods (restriction fragment length polymorphism [RFLP], heteroduplex, and
      direct DNA sequence analyses) for detecting resistance to isoniazid, rifampin,
      and streptomycin and compared these methods with conventional methods for
      susceptibility testing. RFLP analysis detected the mutation at position S315T in
      katG in 12 (44.4%) of 27 isoniazid-resistant strains. Heteroduplex analysis of
      rpoB, detected 16 (76.2%) of 21 rifampin-resistant strains, whereas direct DNA
      sequencing detected all rifampin-resistant strains. RFLP analysis of the rpsL
      gene detected only nine (28.1%) of 32 streptomycin-resistant strains, while
      direct DNA sequencing detected nearly 68% of streptomycin-resistant strains. The
      specificity of all of the above-mentioned methods was excellent. RFLP analysis
      for katG and direct DNA sequencing of rpoB and rpsL may be practical methods for
      routine use in clinical microbiology laboratories or molecular pathology
      laboratories with good molecular capabilities and autosequencers. Despite the
      less than optimal sensitivity for some assays, resistance can be detected
      rapidly. However, molecular methods are not yet capable of replacing more
      traditional methods of susceptibility testing for M. tuberculosis.

PMID- 9142790
TI  - A risk-adapted approach with a short course of ganciclovir to prevent
      cytomegalovirus (CMV) pneumonia in CMV-seropositive recipients of allogeneic bone
      marrow transplants.
AB  - We studied the efficacy and safety of a risk-adapted approach with ganciclovir to
      prevent cytomegalovirus (CMV) pneumonia in 41 CMV-seropositive recipients of
      genotypically human leukocyte antigen-identical bone marrow transplants.
      Prophylaxis with ganciclovir, at a dosage of 2.5 mg/kg twice a day for 14 days,
      was started when patients were treated with high-dose steroids for acute graft
      versus-host disease (i.e., they were considered at high risk for CMV pneumonia),
      or the drug was given as preemptive therapy when CMV antigenemia developed (i.e.,
      the patients were considered at intermediate risk for CMV pneumonia). Twelve
      patients (29%) were treated prophylactically and seven patients (17%)
      preemptively. Only five patients (26%) received a second course of ganciclovir
      (given preemptively to four patients). Twenty-two patients (54%) never received
      ganciclovir because they did not fall within these risk groups. None of the 41
      patients developed CMV pneumonia. Ganciclovir-related granulocytopenia did not
      occur (course 1) or was very mild (course 2). We conclude that this approach
      appears to prevent the development of CMV pneumonia after bone marrow
      transplantation.

PMID- 9142791
TI  - Etiology of solitary pulmonary nodules in patients with human immunodeficiency
      virus infection.
AB  - We assessed 10 patients with human immunodeficiency virus (HIV) infection (nine
      of whom had AIDS) and solitary pulmonary nodules (SPNs) that were detected on
      roentgenograms. Five of the patients presented with respiratory symptoms. The
      etiology of the SPN was determined for eight of these patients: six had
      infections (hydatidosis, mucormycosis, or infection with Nocardia asteroides,
      Cryptococcus neoformans, cytomegalovirus, or Pneumocystis carinii), one had non
      Hodgkin's lymphoma, and the remaining patient had round atelectasis. Sputum
      studies were of no diagnostic value in any of these cases. Fiberoptic
      bronchoscopy with bronchoalveolar lavage and transbronchial biopsy was diagnostic
      in two of seven cases, and percutaneous transthoracic needle biopsy (PTNB) was
      diagnostic in one of four cases. Several microorganisms that were not the cause
      of the SPNs were observed in samples of sputum, bronchoscopic specimens, and PTNB
      specimens. Thoracotomy was diagnostic in the three cases in which it was
      performed. We conclude that the management of SPNs in HIV-infected patients is
      complicated by the low sensitivity and specificity of the diagnostic tests used.

PMID- 9142792
TI  - Staphylococcus aureus prosthetic joint infection treated with debridement and
      prosthesis retention.
AB  - Debridement and retention of the prosthesis was the initial treatment modality in
      30 patients with 33 Staphylococcus aureus prosthetic joint infections (PJIs) who
      presented to the Mayo Clinic between 1980 and 1991. Treatment failure, defined as
      relapse of S. aureus PJI or occurrence of culture-negative PJI during continuous
      antistaphylococcal therapy, occurred in 21 of 33 prosthetic joints. The 1-year
      and 2-year cumulative probabilities of treatment failure were 54% (95% confidence
      interval [CI], 36%-71%) and 69% (95% CI, 52%-86%), respectively. A median of 4
      additional surgical procedures (range, 1-9) were required to control the
      infection in the 21 prosthetic joints for which treatment failed. Prostheses that
      were debrided >2 days after onset of symptoms were associated with a higher
      probability of treatment failure than were those debrided within 2 days of onset
      (relative risk, 4.2; 95% CI, 1.6-10.3). These data suggest that debridement and
      retention of the prosthesis as the initial therapy for PJI due to S. aureus is
      associated with a high cumulative probability of treatment failure and that the
      probability of treatment failure may be related to the duration of symptoms.

PMID- 9142793
TI  - Prevalence of and risk factors for Clostridium difficile colonization at
      admission to an infectious diseases ward.
AB  - A study of 240 consecutive admissions to a single hospital ward over a 6-month
      period was conducted to determine the prevalence of and risk factors for
      Clostridium difficile colonization at admission. The prevalence rate of C.
      difficile colonization at admission was 13.3%. Seventy-four percent of the
      patients admitted to the ward were infected with human immunodeficiency virus
      (HIV). Multivariate analysis identified three risk factors for C. difficile
      colonization: clindamycin use (adjusted odds ratio [OR], 9.4; P < .001),
      penicillin use (adjusted OR, 3.9; P = .018), and a history of cytomegalovirus
      infection (adjusted OR, 4.2; P = .02). C. difficile colonization at admission to
      our infectious diseases ward was common. Antibiotic treatments received before
      admission were the main risk factors for C. difficile colonization. HIV infection
      per se was not associated with C. difficile colonization. It is interesting that
      there was an association between C. difficile colonization and a history of
      cytomegalovirus infection.

PMID- 9142795
TI  - Treatment of multidrug-resistant Acinetobacter baumannii meningitis with
      ampicillin/sulbactam.
AB  - The clinical features and the outcomes of eight cases of nosocomial Acinetobacter
      baumannii meningitis treated with ampicillin/sulbactam are reported. All the
      patients had fever, neck stiffness or meningeal signs, and a low consciousness
      level, and in their cerebrospinal fluid (CSF), pleocytosis, a low glucose level,
      and an elevated protein level were noted. For all CSF isolates of A. baumannii,
      the MIC of ampicillin/sulbactam was < or = 8/4 microg/mL. The MICs of sulbactam
      by microdilution in two cases were 4 microg/mL. All isolates were resistant to
      cefotaxime, ceftriaxone, ceftazidime, ureidopenicillins, ciprofloxacin, and
      gentamicin. Seven isolates were resistant to imipenem. A. baumannii was isolated
      from other samples in seven episodes. All patients were treated with
      ampicillin/sulbactam (seven with 2 g/l g every 6 hours and one with 2 g/l g every
      8 hours). Six patients were cured and two patients died of meningitis. There were
      no side effects with the ampicillin/sulbactam treatment. In conclusion,
      ampicillin/sulbactam may be effective as therapy for meningitis caused by A.
      baumanii resistant to imipenem and other beta-lactam drugs.

PMID- 9142794
TI  - Measles, mumps, rubella, and varicella combination vaccine: safety and
      immunogenicity alone and in combination with other vaccines given to children.
      Measles, Mumps, Rubella, Varicella Vaccine Study Group.
AB  - Eight hundred and twelve children, 12 months to 3.5 years of age, were enrolled
      in two clinical studies to evaluate the safety and immunogenicity of a live,
      attenuated combination vaccine for measles, mumps, rubella, and varicella (MMRV).
      Children were enrolled in one of two randomized, multicenter studies, involving
      administration of (1) MMRV and placebo vs. measles, mumps, and rubella vaccine (M
      M-R(II)) and varicella-zoster virus vaccine (VARIVAX), given at separate anatomic
      sites at the same office visit; or (2) MMRV, DTaP (diphtheria, tetanus, and
      acellular pertussis vaccine) and OPV (oral polio vaccine) vs. M-M-R(II), DTaP,
      and OPV, with VARIVAX given 6 weeks later. All vaccine regimens were generally
      well tolerated. More than 95% of vaccinees seroconverted for measles, mumps,
      rubella, and varicella, regardless of the vaccine or regimen used. In each study,
      the level of antibody titer to varicella virus was significantly lower in
      vaccinees receiving MMRV than in those who received VARIVAX in a separate
      syringe.

PMID- 9142796
TI  - Rapid disease progression in human immunodeficiency virus type 1-infected
      individuals with adverse reactions to trimethoprim-sulfamethoxazole prophylaxis.
AB  - We studied the relation between the occurrence of adverse reactions to
      trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis and the subsequent course of
      human immunodeficiency virus (HIV) infection in a cohort of homosexual men.
      Adverse reactions to TMP-SMZ were associated with a more rapid progression to
      AIDS (P < .001) and death (P < .001) and with a more rapid decline in CD4+ cell
      counts (P = .001). The median time to progression to AIDS was 14.9 months in
      subjects with adverse reactions to TMP-SMZ and 32.5 months in those without
      adverse reactions. After exclusion of Pneumocystis carinii pneumonia (PCP) and
      toxoplasmosis from the case definition of AIDS, the differences in the rate of
      progression to AIDS between subjects with and without adverse reactions to TMP
      SMZ were still highly significant (P = .004). A low CD4+ cell count at baseline
      and the use of antiretroviral agents before the start of prophylaxis were
      predictors of adverse reactions to TMP-SMZ but did not account for the difference
      in progression to AIDS between subjects with and without adverse reactions to TMP
      SMZ. In a univariate analysis, the relative hazard of adverse reactions to TMP
      SMZ for progression to AIDS was 2.54 (95% confidence interval [CI], 1.50-4.28);
      in a multivariate analysis, it was 2.21 (95% CI, 1.29-3.81). The relative hazards
      of adverse reactions to TMP-SMZ for progression to AIDS with the exclusion of PCP
      and toxoplasmosis, CD4+ cell counts of <50/mm3, and death were 2.16 (95% CI, 1.25
      3.72), 2.37 (95% CI, 1.36-4.12), and 3.21 (95% CI, 1.80-5.72), respectively. It
      is unclear whether adverse reactions to TMP-SMZ induce or merely predict
      progression of HIV disease.

PMID- 9142797
TI  - Markedly elevated serum lactate dehydrogenase levels are a clue to the diagnosis
      of disseminated histoplasmosis in patients with AIDS.
AB  - Disseminated histoplasmosis is a common late manifestation of AIDS, but the
      diagnosis may be unsuspected in some patients because the clinical presentation
      of histoplasmosis may mimic other opportunistic infections. High serum lactate
      dehydrogenase (LDH) levels have been associated with disseminated histoplasmosis.
      We therefore evaluated whether markedly increased LDH levels were useful for
      making a diagnosis of disseminated histoplasmosis by comparing admission LDH
      levels for 15 patients with culture-proven disseminated histoplasmosis with those
      for 30 patients with advanced AIDS who were admitted to the hospital for
      evaluation of pulmonary infiltrates and fever. The mean admission LDH level in
      patients with disseminated histoplasmosis was 1,356 IU/L (range, 145-5,410 IU)
      whereas it was 332 (range, 77-832 IU) in the patients with other pulmonary
      processes. Admission LDH levels were >600 IU in 11 (73%) of the 15 patients with
      disseminated histoplasmosis vs. 3 (10%) of controls (P < .001). We conclude that
      markedly elevated admission LDH levels may be a clinical clue to the diagnosis of
      disseminated histoplasmosis in patients with AIDS.

PMID- 9142798
TI  - Prospective analysis of genital ulcer disease in Brooklyn, New York.
AB  - We prospectively studied 82 men and women with first episodes of genital
      ulceration. By using newer diagnostic techniques, a definite microbial etiology
      of 84 infections in 65 of the 82 patients evaluated was found. There were 33
      cases of definite primary syphilis, 27 of definite chancroid, and 24 of definite
      genital herpes simplex. Conclusive evidence of more than one microbial etiology
      was found for 19 (23%) of the patients. Simultaneous primary syphilis and
      chancroid was the third most common ulcer infection. This finding underscores the
      need for both clinical suspicion of multiple infections in patients with genital
      ulcers and comprehensive testing for all suspicious etiologies.

PMID- 9142799
TI  - Temporal association between serum gelsolin levels and clinical events in a
      patient with severe falciparum malaria.
AB  - Actin is present in high concentrations in most eukaryotic cells and can
      polymerize into filaments under physiological buffer conditions. As a result of
      tissue injury and cell lysis, large quantities of actin are released locally and
      may obstruct the downstream microvasculature, causing further damage to already
      injured organs. It has been postulated that this mechanism contributes to the
      development of the adult respiratory distress syndrome and to the diverse
      complications of falciparum malaria. Actin scavenging proteins--e.g., gelsolin-
      counteract the effects of extracellular actin, but the capacity of these plasma
      proteins can be overwhelmed by massive tissue injury. We examined the temporal
      relationship between serum levels of gelsolin (and tumor necrosis factor-alpha)
      and the clinical findings for a patient with severe falciparum malaria. The level
      of gelsolin decreased and then increased as the patient's status first worsened
      and then improved. We could not determine whether gelsolin served a biologically
      important function in this patient's recovery or was simply an epiphenomenon of
      disease activity. Gelsolin levels may be an early prognostic indicator in
      patients with a systemic inflammatory response syndrome. Moreover, the potential
      therapeutic role of recombinant human plasma gelsolin in patients with delayed
      organ dysfunction that commonly follows a self-limited initial insult merits
      investigation.

PMID- 9142800
TI  - Failure to cure Mycobacterium gordonae peritonitis associated with continuous
      ambulatory peritoneal dialysis.
AB  - Nontuberculous mycobacteria are increasingly recognized as important pathogens in
      peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD).
      Mycobacterium gordonae rarely causes human infection and is the least likely
      mycobacterium to produce clinical infection in CAPD patients. We describe a
      patient with persistent M. gordonae peritonitis acquired while undergoing CAPD.
      During 18 months of treatment, clinical improvement occurred but a
      microbiological cure could not be achieved. Principles of therapy for
      mycobacterial peritonitis developing during CAPD are reviewed, and potential
      explanations for our patient's failure to respond to therapy are discussed.

PMID- 9142801
TI  - Relationship of adverse events to serum drug levels in patients receiving high
      dose azithromycin for mycobacterial lung disease.
AB  - We treated 39 elderly human immunodeficiency virus-noninfected patients with
      Mycobacterium avium complex and/or Mycobacterium abscessus lung disease with
      azithromycin (600 mg daily), given initially as monotherapy. Adverse events
      occurred in 33 of 39 patients (85%) receiving azithromycin alone, most commonly
      gastrointestinal (GI) symptoms (32 of 39, or 82%) and hearing impairment (10 of
      39, or 26%). Twenty-four of 39 patients (62%) required a lower dose or withdrawal
      of the drug. The mean serum level in patients who required a dose reduction
      because of hearing impairment was 0.8 +/- 0.4 microg/mL, and that in patients
      whose reduction was necessitated by GI symptoms was 0.7 +/- 0.4 microg/mL; in
      comparison, the mean serum level was 0.3 +/- 0.16 microg/mL in patients with no
      adverse events (P = .004 and .003, respectively). Decreasing the daily dose to
      300 mg resulted in resolution of most adverse events. Serum levels with
      monotherapy were comparable to levels after the addition of other antituberculous
      drugs that included rifampin or rifabutin. Thus, a 300-mg rather than 600-mg
      daily dose of azithromycin is better tolerated by elderly patients, and serum
      levels appear unaffected by other antituberculous agents, including rifampin.

PMID- 9142802
TI  - Acute human immunodeficiency virus type 1 disease as a mononucleosis-like
      illness: is the diagnosis too restrictive?
AB  - The purpose of this study was to describe the frequency and duration of clinical
      features at the time of acute human immunodeficiency virus type 1 (HIV-1) disease
      in 218 patients with documented symptomatic primary HIV-1 infection. The mean
      duration of acute HIV-1 disease was 25.1 days (median, 20.0 days) and did not
      differ by gender, age, and risk factor. The frequency and mean duration of
      clinical features occurring in >50% of patients were as follows: fever, 77.1% and
      16.9 days; lethargy, 65.6% and 23.7 days; cutaneous rash, 56.4% and 15 days;
      myalgia, 54.6% and 17.7 days; and headache, 50.9% and 25.8 days. Only 15.6% of
      patients presented with a typical mononucleosis-like illness (MLI) defined as
      fever, pharyngitis or sore throat, and cervical adenopathy, and 10% had no
      features of an MLI. A meningitis-like syndrome occurred in 20 patients (9.2%).
      Acute HIV-1 disease is more diverse than previously reported, and the absence of
      fever or other MLI features does not rule out acute HIV-1 disease.

PMID- 9142803
TI  - The clinical course of human immunodeficiency virus infection in genetically
      identical children.
AB  - Human immunodeficiency virus (HIV) infection in children is associated with
      diverse clinical manifestations and highly variable rates of progression. There
      is little information concerning the clinical course of HIV infection in
      genetically identical children. We review the cases of identical triplets who
      were infected with HIV at 1 day of age via a blood transfusion from a common unit
      of contaminated blood. The subsequent clinical manifestations of HIV infection in
      the triplets were remarkably uniform. Moreover, the patients' CD4 cell counts
      declined at similar rates. These patients enhance our understanding of the role
      of viral and host factors in determining the clinical progression of HIV
      infection.

PMID- 9142804
TI  - Progression of human immunodeficiency virus infection in children is related to
      the interaction of the virus, the immune system, and then some.

PMID- 9142805
TI  - Epidemiology and treatment of Cyclospora cayetanensis infection in Peruvian
      children.
AB  - Cyclospora cayetanensis was detected in fecal specimens from 63 (1.1%) of 5,836
      Peruvian children studied over 2 years; the protozoan was detected by modified
      acid-fast staining and autofluorescence under ultraviolet light. The highest
      prevalence occurred among children between 2 and 4 years of age. Thirty-two
      percent (20) of the 63 C. cayetanensis-infected children were symptomatic.
      Nineteen infected children were enrolled in a double-blind, placebo-controlled
      trial of a 3-day course of trimethoprim-sulfamethoxazole (TMP-SMZ; 5/25 mg/[kg x
      d]). Children were followed up with daily stool examinations (mean number of
      samples examined per child +/- SE, 19 +/- 4). The mean duration of oocyst
      excretion +/- SE was 4.8 +/- 1.2 days for TMP-SMZ recipients compared with 12.1
      +/- 6.1 days for placebo recipients (P < .02). The prevalence of C. cayetanensis
      infection decreases during winter months and as children age; it decreases
      precipitously by adulthood. In children in areas of endemicity, C. cayetanensis
      usually causes mild disease that is often asymptomatic. TMP-SMZ therapy
      significantly decreases the duration of oocyst excretion.

PMID- 9142806
TI  - Fatal disseminated Mycobacterium smegmatis infection in a child with inherited
      interferon gamma receptor deficiency.
AB  - Mycobacterium smegmatis is a common environmental mycobacterium that was first
      identified in 1884, yet is a rare pathogen in humans. The few M. smegmatis
      infections reported to date have been localized and have occurred in association
      with a primary lesion in otherwise immunocompetent individuals. To our knowledge,
      no case of disseminated M. smegmatis infection has ever been reported, even in
      patients with severe immune deficiencies. We report a case of disseminated
      mycobacterial infection that was diagnosed in a 3-year-old girl. The pathogen was
      not identified as M. smegmatis until the patient was 6 years old. Her condition
      gradually worsened, and she died when she was 8 years old despite appropriate
      antimycobacterial therapy. No other opportunistic infections were documented.
      Immunological investigations revealed an inherited interferon gamma receptor 1
      deficiency. This report identifies M. smegmatis as a new opportunistic agent that
      may be responsible for disseminated disease in immunocompromised individuals.

PMID- 9142807
TI  - Polymerase chain reaction analysis of distal vaginal specimens: a less invasive
      strategy for detection of Trichomonas vaginalis.
AB  - We compared polymerase chain reaction (PCR) analysis of specimens obtained from
      the distal vagina with wet mount microscopy and culture of specimens from the
      posterior vaginal fornix. One or all three techniques revealed that 61 (20.3%) of
      300 women tested were positive for Trichomonas vaginalis. PCR analysis of distal
      vaginal specimens detected 56 (91.8%) of 61 infections, while wet mount
      microscopy and culture detected 49 (80.3%) of 61 infections. Results of this
      study may impact the approach to testing for T. vaginalis by eliminating the
      requirement of a vaginal speculum examination. The distal vagina is an
      appropriate testing site for T. vaginalis by PCR analysis.

PMID- 9142808
TI  - CD4 cell counts in human immunodeficiency virus-negative patients with
      tuberculosis.
AB  - We evaluated 85 human immunodeficiency virus (HIV)-negative patients with
      tuberculosis for clinical features and CD4 cell counts. Thirty-seven patients had
      low CD4 cell counts (mean +/- SD, 341 +/- 116 cells/microL), and 48 patients had
      normal CD4 cell counts (mean +/- SD, 830 +/- 254 cells/microL). CD4 cell counts
      were most strongly correlated with total lymphocyte counts (r = 0.84). If total
      lymphocyte count was excluded, depressed CD4 cell counts were significantly
      associated with low serum albumin levels, extensive pulmonary disease, low body
      mass index, and low hematocrit. Of these four variables, multivariate linear
      discriminant analysis revealed that the serum albumin level was the best single
      predictor of low CD4 cell counts and that the other three variables did not
      improve predictive value. Because these four variables are markers of severe
      tuberculosis, these findings suggest that disease severity is associated with
      greater depression of the total lymphocyte and CD4 cell counts. The CD4 cell
      counts returned to normal levels in most patients after 1 month of therapy.

PMID- 9142809
TI  - Early therapy with interferon for acute hepatitis C acquired through a
      needlestick.
AB  - Because there is no effective neutralizing antibody or vaccine for preventing
      hepatitis C virus (HCV) transmission, HCV can be transmitted to health care
      workers through accidental needlesticks. Recently, two of our health care workers
      acquired HCV infection through needlestick accidents and developed acute
      hepatitis C. The route of transmission was confirmed by molecular evolutionary
      analysis with use of the E2 region of the HCV genome. After the clinical onset of
      acute hepatitis, the health care workers were treated with interferon (IFN)
      (total dose, approximately 300 megaunits). Neither individual developed chronic
      hepatitis. This finding raises the possibility that treatment with low-dose IFN
      following an accidental needlestick may be beneficial, even when it is started
      after the clinical onset of hepatitis.

PMID- 9142810
TI  - Osteomyelitis due to Mycobacterium haemophilum in a cardiac transplant patient:
      case report and analysis of interactions among clarithromycin, rifampin, and
      cyclosporine.
AB  - We describe a case of osteomyelitis due to Mycobacterium haemophilum in a cardiac
      transplant recipient and review the two other reported cases of M. haemophilum
      infection in cardiac transplant patients. Our patient had an excellent response
      to a prolonged course of therapy with clarithromycin and rifampin. We examine in
      detail the interactions between these two antibiotics and cyclosporine, including
      the apparently offsetting effects of clarithromycin/rifampin combination therapy
      on blood levels of cyclosporine.

PMID- 9142811
TI  - Characteristics of typhoid fever in children and adolescents in a major
      metropolitan area in the United States.
AB  - To examine the epidemiology of typhoid fever in children in an area that was not
      endemic, we analyzed 55 cases of typhoid fever in children and adolescents who
      were < or = 18 years and whose cases were reported to the Chicago and suburban
      Cook County Health Departments over 7 years. Cases had positive blood and/or
      stool cultures for Salmonella typhi. The ethnic distribution of the patients was
      as follows: 25% Asian, 22% Hispanic, 15% African American, 9% Caucasian, 18%
      other, and 11% unknown. Of the 55 cases, 35% were aged 0-5 years, 25% were aged 6
      10 years, 31% were aged 11-15 years, and 9% were aged 16-18 years. Twelve
      patients did not have a history of travel. All patients recovered; none became
      carriers. Symptoms in 41 patients whose charts were available for review included
      fever (100%), diarrhea (77%), vomiting (50%), and dehydration (30%). Bacteremia
      was documented in 27 (66%) of 41 cases. In 17 of 41 cases, the household contacts
      were food handlers or health care workers. Eight (31%) of 26 isolates were
      resistant to both ampicillin and trimethoprim-sulfamethoxazole. The findings in
      our study were as follows: typhoid fever occurred frequently in children aged 0-5
      years (in contrast with reports from areas of endemicity), approximately 20% of
      patients did not have a history of travel, and multidrug-resistant strains were
      prevalent.

PMID- 9142812
TI  - Infectious complications of hepatic cryosurgery.
AB  - Hepatic cryosurgery is a novel procedure for patients with metastatic liver
      disease. To date, no reviews of the infectious complications of this procedure
      have been published. One hundred and fifty patients underwent 158 hepatic
      cryosurgical procedures at Allegheny General Hospital (Pittsburgh) from November
      1987 through July 1995. Gastrointestinal malignancies accounted for 93% of the
      underlying diagnoses. The following 12 infections were directly related to the
      cryosurgical procedure: hepatic abscess (six), intraperitoneal abscess (three),
      ascending cholangitis (two), and an intrahepatic device (Infusaid;
      Strato/Infusoid, Norwood, MA) infection (one). Enterococcus was the most commonly
      isolated organism. Seven of the 12 infections were polymicrobial. The patients
      who developed infections had longer hospital stays (26 days vs. 13 days) and had
      more days of fever (6.5 days vs. 2.3 days). than those who did not develop
      infections. If perioperative manipulation of the biliary tree is avoided, the
      infection rate in patients who undergo hepatic cryosurgery may be decreased even
      further. Overall, cryoablation of the liver is not related to an increased risk
      of infection.

PMID- 9142813
TI  - Use of random amplification of polymorphic DNA in a case of Pasteurella multocida
      meningitis that occurred following a cat scratch on the head.
AB  - We cultured Pasteurella multocida from the cerebrospinal fluid (CSF) of a 4-month
      old infant who presented with meningitis. The patient had been scratched on the
      head by a cat. Culture of the cat's claws also yielded P. multocida. The isolates
      had identical biochemical patterns. Analysis of both strains by random
      amplification of polymorphic DNA and comparison of these strains with P.
      multocida strains isolated from other cats showed that the two strains were
      identical and completely different from the unrelated isolates. Our patient's
      meningitis most likely resulted from direct inoculation of P. multocida into the
      CSF.

PMID- 9142814
TI  - Methylobacterium mesophilicum synovitis in an alcoholic.

PMID- 9142815
TI  - Salmonella parotitis with abscess formation in a patient with human
      immunodeficiency virus infection.

PMID- 9142816
TI  - Role of aerobic and anaerobic bacteria in pacemaker infections.

PMID- 9142817
TI  - Brucella melitensis osteitis following craniotomy in a patient with AIDS.

PMID- 9142818
TI  - Prosthetic valve endocarditis due to Veillonella dispar: successful medical
      treatment following penicillin desensitization.

PMID- 9142819
TI  - Pacemaker infection caused by Staphylococcus schleiferi, a member of the human
      preaxillary flora: four case reports.

PMID- 9142820
TI  - Sterile, caseous mitral valve "abscess" mimicking infective endocarditis.

PMID- 9142821
TI  - Spontaneous pyomyositis due to Staphylococcus epidermidis.

PMID- 9142822
TI  - Tuberculosis of the rib.

PMID- 9142823
TI  - Campylobacter fetus-associated aneurysms: report of a case involving the
      popliteal artery and review of the literature.

PMID- 9142824
TI  - Isolated septic arthritis due to Streptococcus bovis.

PMID- 9142825
TI  - Symptomatic primary infection with human herpesvirus 6 variant A.

PMID- 9142826
TI  - Resolution of intractable molluscum contagiosum in a human immunodeficiency virus
      infected patient after institution of antiretroviral therapy with ritonavir.

PMID- 9142827
TI  - Tuberculosis and human T-cell lymphotropic virus type 1 infection.

PMID- 9142828
TI  - Penicillium marneffei infection associated with AIDS.

PMID- 9142829
TI  - Human immunodeficiency virus as an infectious cause of pharyngitis.

PMID- 9142830
TI  - Leukopenia, thrombocytopenia, and Lyme borreliosis: is there an association?

PMID- 9142831
TI  - Bowditch lecture. Integrated regulation of intestinal epithelial transport:
      intercellular and intracellular pathways.
AB  - The intestinal epithelium is an important site of active solute transport
      processes. Such processes include the secretion of electrolytes into the lumen,
      predominantly chloride and bicarbonate. These secretory mechanisms subserve a
      variety of functions, both physiological and pathophysiological, including
      maintenance of the fluidity of intestinal contents and mucosal defense. Both
      chloride and bicarbonate secretion are the subject of integrated regulatory
      mechanisms at both the intercellular and intracellular levels. The goal of this
      article is to discuss data that exemplify these two levels of regulation, which
      have been the subject of research in my laboratory. It is likely that some of
      these principles are also broadly applicable to secretory epithelial cells
      outside of the intestinal tract, such as those in the airway. I also discuss the
      ways in which we believe these regulatory mechanisms are involved not only in
      intestinal physiology but also perhaps in the pathogenesis of specific disease
      states.

PMID- 9142832
TI  - Role of actin in regulation of epithelial sodium channels by CFTR.
AB  - Cystic fibrosis (CF) airway epithelia exhibit enhanced Na+ reabsorption in
      parallel with diminished Cl- secretion. We tested the hypothesis that actin plays
      a role in the regulation of a cloned epithelial Na+ channel (ENaC) by the cystic
      fibrosis transmembrane conductance regulator (CFTR). We found that immunopurified
      bovine tracheal CFTR coreconstituted into a planar lipid bilayer with
      alpha,beta,gamma-rat ENaC (rENaC) decreased single-channel open probability (Po)
      of rENaC in the presence of actin by over 60%, a significantly greater effect
      than was observed in the absence of actin (approximately 20%). In the presence of
      actin, protein kinase A plus ATP activated both CFTR and rENaC, but CFTR was
      activated in a sustained manner, whereas the activation of rENaC was transitory.
      ATP alone could also activate ENaC transiently in the presence ofactin but had no
      effect on CFTR. Stabilizing short actin filaments at a fixed length with gelsolin
      (at a ratio to actin of 2:1) produced a sustained activation of alpha,beta,gamma
      rENaC in both the presence or absence of CFTR. Gelsolin alone (i.e., in the
      absence of actin) had no effect on the conductance or Po of either CFTR or rENaC.
      We have also found that short actin filaments produced their modulatory action on
      alpha-rENaC independent of the presence of the beta- or gamma-rENaC subunits. In
      contrast, CFTR did not affect any properties of the channel formed by alpha-rENaC
      alone, i.e., in the absence of beta- or gamma-rENaC. These results indicate that
      CFTR can directly downregulate single Na+ channel activity, which may account for
      the observed differences between Na+ transport in normal and CF-affected airway
      epithelia. Moreover, the presence of actin confers an enhanced modulatory ability
      of CFTR on Na+ channels.

PMID- 9142833
TI  - Calcium removal kinetics of the sarcoplasmic reticulum ATPase in skeletal muscle.
AB  - The models of the sarcoplasmic reticulum (SR) Ca pump used to simulate Ca
      kinetics in muscle fibers are simple but inconsistent with data on Ca binding or
      steady-state uptake. We develop a model of the SR pump that is consistent with
      data on transient and steady-state Ca removal and has rate constants identified
      under near-physiological conditions. We also develop models of the other main Ca
      binding proteins in skeletal muscle: troponin C and parvalbumin. These models are
      used to simulate Ca transients in cut fibers during and after depolarizing
      pulses. Simulations using the full SR pump model are contrasted with simulations
      using a Michaelis-Menten (MM) approximation to SR pump kinetics. The MM pump
      underestimates the amount of Ca released during depolarization, underestimates
      the initial rate of Ca binding by the pump, and overestimates the later rate of
      Ca pumping. These errors are due to fast initial binding by the SR pump, which is
      neglected in the MM approximation.

PMID- 9142834
TI  - Defining the volume dependence of multiple K flux pathways of trout red blood
      cells.
AB  - The volume sensitivity of different K flux pathways has been determined in trout
      red blood cells subjected to volume perturbation. Gentle hyposmotic swelling
      induced a K influx in a Cl-containing saline but not in NO3- or methanesulfonate
      (MeSF)-containing salines, consistent with the activation of a Cl-dependent flux.
      Extreme hyposmotic swelling led to larger K fluxes in all salines but with
      reduced anion discrimination of the Cl-dependent flux. In contrast to these
      graded responses, isosmotic swelling using ammonium chloride or beta-adrenergic
      stimulation activated only Cl-dependent fluxes in an all-or-none fashion. The
      relationship between the hyposmotically and isosmotically induced pathways was
      studied by coactivation using either ammonium chloride or isoproterenol with
      anisosmotic treatment. Cells in ammonium chloride-containing hyposmotic salines
      showed no additive K flux over that induced by hyposmotic treatment alone,
      indicating that the isosmotically induced Cl-dependent flux was identical to the
      hyposmotically induced Cl-dependent flux. However, cells coactivated by
      hyposmotic and beta-adrenergic treatment showed a small Cl-dependent flux in
      addition to that induced by hyposmotic treatment alone. This small third
      component was unaffected by anisosmotic treatment. We conclude that the major Cl
      dependent and Cl-independent K flux pathways are distinct and separate and that
      the former has an anion dependence that varies with cell volume and a volume
      sensitivity that varies with ionic strength.

PMID- 9142835
TI  - Thrombin modulates vectorial secretion of extracellular matrix proteins in
      cultured endothelial cells.
AB  - We have identified a novel cellular action of thrombin on cultured rat adrenal
      medullary endothelial cells (RAMEC). Five-minute incubation of RAMEC with
      physiological concentrations of thrombin (<1 U/ml) caused within 3 h an increase
      in the basolateral deposition of the extracellular matrix (ECM) proteins
      fibronectin, laminin, and collagens IV and I, concomitant with a corresponding
      decrease in the apical release of these proteins into the medium. This shift in
      vectorial secretion of ECM proteins, quantitated with enzyme-linked immunoassays,
      was time dependent. Maximal stimulation of ECM protein deposition was observed
      after incubation of cells with thrombin for 5-15 min. Prolonged exposure (>1 h)
      to thrombin resulted in loss of proteins from the ECM. Thrombin-stimulated ECM
      protein deposition exhibited a bell-shaped dose dependence, peaking for all
      proteins at 0.25 U/ml of thrombin, and was independent of de novo mRNA or protein
      synthesis. Maximal amounts of deposited proteins increased between 2.5-fold
      (fibronectin) and 4-fold (collagen I) over baseline values. Similar results were
      obtained with thrombin receptor agonist peptide (TRAP), proteolytically active
      gamma-thrombin, and, to a lesser extent, other serine proteases such as trypsin
      and plasmin. A scrambled TRAP, proteolytically inactive PPACK-thrombin, DIP
      thrombin, and type IV collagenase were ineffective. Together, these results
      suggest that the thrombin effects are mediated by proteolytic activation of the
      thrombin receptor. Possible involvement of the phospholipase C-signaling pathway
      in thrombin-mediated ECM protein deposition was also investigated. Inhibition or
      downregulation of protein kinase C (PKC) and chelation of intracellular or
      extracellular Ca2+ did not suppress, but rather enhanced, basal and thrombin
      stimulated ECM protein deposition. Quantitative differences in augmentation of
      basolateral deposition by these treatments suggest differential regulatory
      pathways for individual ECM proteins. Our data indicate that, in cultured RAMEC,
      short-term activation of the thrombin receptor causes an increase in amounts of
      deposited ECM protein by a cellular signaling pathway that is independent of PKC
      activation and/or elevation of intracellular Ca2+.

PMID- 9142836
TI  - Cholera and pertussis toxins increase acidification of endocytic vesicles without
      altering ion conductances.
AB  - Acidification of endocytic vesicles, driven by the vacuolar H+ pump, is affected
      by parallel ion transporters. Because adenosine 3',5'-cyclic monophosphate (cAMP)
      and heterotrimeric G proteins may alter ion transporters, I tested whether
      cholera and pertussis toxins affected acidification of rat liver endosomes.
      Fluorescein-labeled dextran-loaded "10-min" endosomes from cholera toxin-treated
      rats exhibited ATP-dependent rates of acidification in the presence and absence
      of Cl- or K+ that were approximately 60-120% (P < 0.05) faster than rates from
      control endosomes. This increase was greater for "older" "20-min" endosomes and
      less for 'early" "2-min" endosomes. Ion transport functions of 10-min and 20-min
      toxin-exposed endosomes were similar to those of 2-min control endosomes. Cholera
      toxin also increased ATP-dependent steady-state intravesicular H+ concentration
      by 38-218% (P < 0.05). Pertussis toxin increased endosome acidification rates by
      20-54% (P < 0.05). Both toxins increased liver cAMP content, and endosomes
      prepared from perfused livers exposed to 0.75 mM dibutyryl cAMP exhibited similar
      increases in acidification rates. These studies indicate that both cholera and
      pertussis toxins markedly alter the function of rat liver endosomes. The
      mechanism is unlikely to reflect major changes in vesicle ion transporters but
      rather may indicate either an increase in the number of H+ pumps per endosome
      and/or changes in fusion, remodeling, and maturation of early endocytic vesicles
      in response to cAMP.

PMID- 9142837
TI  - Chondrocytes in the endochondral growth cartilage are not hypoxic.
AB  - From an anatomic viewpoint, the blood supply to chondrocytes in the growth
      cartilage is limited. As a result, it has been suggested that these cells are
      hypoxic and that this condition regulates chondrocyte maturation and cartilage
      mineralization. We examined the state of chondrocyte oxygenation in the chick
      growth plate using a hypoxia-sensing drug, EF5. EF5 is a pentafluorinated
      derivative of the 2-nitroimidazole, etanidazole, that is metabolically reduced by
      oxygen-inhibitable nitroreductase(s). Reduced EF5 covalently forms adducts with
      cellular macromolecules that can be visualized with a highly specific
      fluorochrome-conjugated monoclonal antibody. When EF5 was injected into chicks
      and tissues were subsequently examined by immunohistochemical techniques,
      chondrocytes in articular, proliferating, and hypertrophic cartilage exhibited a
      low level of fluorescence-detectable binding, suggesting the absence of
      significant hypoxia. We confirmed that the results were not confounded by tissue
      specific factors related to low-chondrocyte nitroreductase activity or problems
      from drug diffusion into cartilage. Using in vitro systems, we showed that, under
      conditions of imposed hypoxia, EF5 diffused into the tissue and was bound to
      chondrocytes. With the use of an in vivo model in which hypoxia was artificially
      induced by death, chick chondrocytes were found to bind the drug. Although the
      EF5-binding method is not optimally suited for determining the precise oxygen
      partial pressure in heterogeneous tissues, such as the growth plate, we concluded
      that chick chondrocytes are not oxygen deficient in vivo.

PMID- 9142838
TI  - Myosin isoform expression and force generation in cultured resistance arteries.
AB  - Organ culture of mesenteric resistance arteries results in a loss of force
      generating ability, which is prevented by 1alpha,25-dihydroxyvitamin D3
      [1,25(OH)2D3]. We have tested the hypothesis that the culture-induced decrease in
      active stress is associated with altered myosin isoform expression. Rat
      mesenteric resistance arteries were studied immediately (fresh) or after
      incubation at 37 degrees C for 48 h in culture medium (control), with 300 pg/ml
      1,25(OH)2D3, or with 5 microg/ml insulin. Isometric force was measured by
      myography; myosin heavy chain (MHC) and regulatory myosin light chain isoform
      (MLC) contents were determined using sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. Maximal active stress to 100 mM K+ (mN/mm2) was greater for
      fresh (147.8 +/- 4.9) than control (109.2 +/- 4.6, P = 0.001) or insulin (79.6 +/
      8.6, P < 0.001) but not 1,25(OH)2D3 (137.4 +/- 9.5, P = 0.197). Organ culture
      did not alter MLC or MHC smooth muscle (SM)-1 isoform content. MHC SM-2 content
      (nmol/mg protein) was greater in fresh (0.038 +/- 0.003) than control (0.026 +/-
      0.003, P = 0.012) and insulin (0.027 +/- 0.002, P = 0.018) but not 1,25(OH)2D3
      (0.036 +/- 0.003, P = 0.693); nonmuscle MHC (NMM) was observed in insulin. The
      maximal active stress response to K+ significantly correlated with SM-2 MHC
      isoform content (r2 = 0.483, P < 0.001). We conclude that 1) arterial organ
      culture alters MHC isoform content, 2) SM-2 MHC isoform content positively
      correlates with active stress generation, 3) 1,25(OH)2D3 maintains force
      generating capacity by preventing the shift of MHC isoform expression, and 4)
      insulin impairs force-generating ability by lowering MHC SM-2 content and
      stimulating NMM expression.

PMID- 9142839
TI  - Modulation of maxi-K+ channels by voltage-dependent Ca2+ channels and
      methacholine in single airway myocytes.
AB  - The role of Ca2+ influx through voltage-dependent Ca2+ channels and the
      inhibitory effects of methacholine on large-conductance Ca2+-activated K+ (K(Ca))
      channels (maxi-K+ channels) were studied in voltage-clamped (nystatin), fura 2
      loaded airway smooth muscle cells. Spontaneous transient outward currents (STOCs)
      were strongly coupled to voltage-dependent Ca2+ channel activity; activity was
      suppressed by nisoldipine and Cd2+ and increased by BAY K 8644 within seconds.
      Moreover, release of intracellular Ca2+ by caffeine or cyclopiazonic acid only
      partially suppressed STOCs, and the remainder were almost completely blocked by
      nisoldipine. Methacholine suppressed STOCs but also significantly decreased the
      mean outward current. Whole cell current inhibition was observed in the presence
      of 4-aminopyridine but not in the presence of charybdotoxin. Caffeine inhibited
      STOCs but macroscopic outward currents were not altered. In the continued
      presence of caffeine, methacholine abolished the remaining STOCs and decreased
      the mean K+ current. We conclude that STOCs are activated by influx of Ca2+
      through plasmalemmal voltage-dependent Ca2+ channels, as well as by release of
      Ca2+ from intracellular stores, and muscarinic stimulation depresses the mean
      K(Ca) current via a pathway independent of the depletion of intracellular Ca2+
      stores.

PMID- 9142840
TI  - Ins(3,4,5,6)P4 specifically inhibits a receptor-mediated Ca2+-dependent Cl-
      current in CFPAC-1 cells.
AB  - We have examined the role of inositol 3,4,5,6-tetrakisphosphate [Ins(3,4,5,6)P4]
      in the control of Cl- current in CFPAC-1 cells. Intracellular Ins(3,4,5,6)P4 had
      no effect on basal current, but it produced a five- to sevenfold reduction in the
      Cl- current stimulated by either 2 microM extracellular ATP or by 1 microM
      extracellular thapsigargin. The half-maximally effective dose of Ins(3,4,5,6)P4
      was 2.9 microM, and 4 microM blocked >80% of the ATP-activated current. In
      contrast, 10 microM Ins(1,4,5,6)P4, Ins(1,3,4,5)P4, or Ins(1,3,4,6)P4 enhanced
      rather than inhibited the ATP-activated Cl- current, although Ins(1,4,5,6)P4 only
      acted transiently. These stimulatory effects were Ca2+ dependent and largely
      inhibited by coapplication of equimolar Ins(3,4,5,6)P4. Inositol 1,3,4,5,6
      pentakisphosphate, the precursor of Ins(3,4,5,6)P4, did not affect Cl- current.
      These data consolidate and extend the hypothesis that Ins(3,4,5,6)P4 is an
      important intracellular regulator of Cl- current in epithelial cells.

PMID- 9142841
TI  - Purinergic-mediated inhibition of Na+-K+-ATPase in proximal tubule cells:
      elevated cytosolic Ca2+ is not required.
AB  - The involvement of cytosolic Ca2+ concentration ([Ca2+]i) as messenger for the
      regulation of Na+-K+-ATPase activity was investigated in a renal cell line
      recently developed by immortalization of early proximal tubule primary cultures
      from the Wistar-Kyoto rat strain. Na+-K+-ATPase was measured as short-circuit
      current (Isc) in intact monolayers after permeabilization of the apical plasma
      membrane with amphotericin B. With symmetrical solutions, Isc quantitatively
      reflects Na+-K+-ATPase activity as judged by ouabain inhibition and dependence on
      Na+ and K+. Extracellular ATP (50% effective concentration = 0.32 mM) on the
      apical side produced acute inhibition of Na+-K+-ATPase-generated Isc of up to
      50%. The inhibition peaked within 1 min and lasted approximately 5 min. The
      potency order was ATP > ADP >> beta,gamma-methyleneadenosine 5'-triphosphate =
      UTP, consistent with a P2y receptor. Extracellular ATP also stimulated a
      transient increase in [Ca2+]i. This increase had a similar time course as the
      inhibition of ATPase and reached a peak change of approximately 120 nM. However,
      the elevation of [Ca2+]i is not required in the purinergic inhibition of the Na+
      K+-ATPase, since, first, increases in [Ca2+]i produced with a Ca2+ ionophore
      (ionomycin) failed to mimic the purinergic inhibition and, second, 1,2-bis(2
      aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid, which abolished the [Ca2+]i
      elevation, failed to block the purinergic inhibition.

PMID- 9142842
TI  - Modulation of voltage-dependent Ca2+ conductance by changing Cl- concentration in
      rat lactotrophs.
AB  - In pituitary cells, voltage-dependent Ca2+ channels play an important role in
      such physiological processes as exocytosis, secretion, the cell cycle, and
      proliferation. Thus mechanisms that modulate voltage-dependent Ca2+ channel
      activity participate indirectly in regulating intracellular Ca2+ concentration.
      We have shown a new modulating mechanism for voltage-dependent Ca2+ channels by
      demonstrating that Ca2+ influx is influenced by Cl-. To evaluate the role of Cl-
      on Ca2+ conductance coupling, we first measured the intracellular Cl-
      concentration of rat lactotrophs using the Cl(-)-sensitive fluorescence probe
      sulfopropylquinolinium by simple microspectrofluorometry or combined with
      electrophysiology. We found an average intracellular Cl- concentration of rat
      lactotrophs of approximately 60 mM (n = 39). Using the whole cell tight-seal
      recording technique, we showed that a reduction in external Cl- concentration
      ([Cl-]o) and a decrease in Cl- conductances affected Ca2+ conductance as measured
      by Ba2+ movement through the Ca2+ channels (I(Ba)). Low [Cl-]o (39 mM) induced a
      decrease in Ca2+ entry via voltage-gated Ca2+ channels (-27.75 +/- 4% of
      normalized I(Ba)). Similarly, blockade of the Cl- conductance by 1 mM 9
      anthracene carboxylic acid induced a decrease in I(Ba) (-26 +/- 6% of normalized
      I(Ba)). This modulation of I(Ba) was inhibited by 24-h pretreatment of the cells
      with pertussis toxin (1 microg/ml), suggesting that changes in Cl- concentration
      induced by low [Cl-]o and 9-anthracene carboxylic acid interfered with the
      phosphorylation of G proteins involved in Ca2+ channel activation. These results
      suggest a feedback mechanism based on constant interaction between Ca2+ and Cl-.
      Finally, they also emphasize the physiological role of Cl- in rat lactotrophs.

PMID- 9142843
TI  - Electrogenic Li+/Li+ exchange mediated by the Na+-K+ pump in rabbit cardiac
      myocytes.
AB  - The membrane Na+-K+ pump can be activated at extracellular sites by several
      different monovalent cations, including Li+, while being highly selective for the
      physiological activator Na+ at intracellular sites. We examined whether Li+ can
      replace Na+ as an activator of the Na+-K+ pump at intracellular sites. Single
      cardiac myocytes were voltage clamped at 0 mV with wide-tipped patch pipettes
      filled with a K+- and Na+-free solution containing 160 mM Li+. Ouabain induced an
      inward shift of membrane current when the myocytes were superfused with Na+
      Tyrode solution containing 5.6 mM K+. The shift was dependent on the presence of
      intracellular Li+ (LiCl in pipette filling solution replaced with
      tetramethylammonium chloride) and extracellular K+. When we replaced Na+ and K+
      in the superfusate with Li+ and voltage clamped myocytes using Li+-containing
      filling solutions in patch pipettes, ouabain induced an inward shift in membrane
      current similar to that recorded when myocytes were superfused with K+-containing
      Na+-Tyrode solution. These findings indicate that the Na+-K+ pump can mediate
      electrogenic exchange of intracellular Li+ for extracellular K+ or Li+.

PMID- 9142844
TI  - Expression of functional mitochondrial creatine kinase in liver of transgenic
      mice.
AB  - The mitochondrial isoform of creatine kinase (MiCK) is localized to the
      mitochondrial intermembrane space, and its precise role in vivo is still actively
      being investigated. Here, we report a transgenic mouse model in which MiCK is
      expressed in liver, a tissue that does not normally express significant levels of
      CK. Expression of the genomic clone for human, ubiquitous MiCK was controlled by
      the promoter/enhancer region of the transthyretin gene. Three of seven founder
      mice were chosen to establish lines and had MiCK activity values ranging from 13
      to 269 micromol x min(-1) x g wet wt(-1). Differential centrifugation and
      histochemical staining demonstrated that >90% of the CK activity is localized to
      the mitochondrial intermembrane space. An unusual mitochondrial morphology
      characterized by an angular nature to the membranes was detected using electron
      microscopy in the transgenic line expressing the highest levels of MiCK.
      Increasing hepatic total creatine levels led to a return to normal mitochondrial
      morphology. 31P-nuclear magnetic resonance spectroscopy demonstrated that the
      expressed MiCK is capable of producing and utilizing phosphocreatine. These mice
      will be useful for investigating gain of function effects of MiCK in cellular
      energetics.

PMID- 9142845
TI  - Fatty acid modulation of K+ channels in taste receptor cells: gustatory cues for
      dietary fat.
AB  - In an attempt to determine the chemosensory cues, if any, provided by fats in the
      oral cavity, we have performed patch-clamp recordings on isolated rat taste
      receptor cells during application of free fatty acids. Cis-polyunsaturated fatty
      acids, when applied extracellularly, inhibit delayed-rectifying K+ channels. In a
      subset of cells, these fatty acids also enhance inwardly rectifying K+ currents.
      Saturated, monounsaturated, and trans-polyunsaturated fatty acids have no
      significant effect on K+ currents. These effects do not involve activation of G
      protein-mediated pathways, including protein kinase C and protein kinase A,
      lipoxygenase pathways, cyclooxygenase pathways, or cytochrome P-450 pathways,
      consistent with direct effects on these ion channels or closely associated
      proteins. The net effect of fatty acids is to prolong stimulus-induced
      depolarizations of taste receptor cells, and we propose the effects on K+
      channels represent the mechanism by which fats are detected by receptor cells in
      the oral cavity.

PMID- 9142846
TI  - A caffeine-sensitive Ca2+ store modulates K+-evoked secretion in chromaffin
      cells.
AB  - Catecholamine release from bovine adrenal medulla chromaffin cells superfused
      with a Krebs-N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid solution was
      monitored on-line with an electrochemical detector. Caffeine (10 mM)
      progressively depressed the magnitude of secretory responses to depolarizing
      pulses of 70 mM K+ and 2 mM Ca2+ (70 K+/2 Ca2+) in cells superfused with a Krebs
      N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid solution containing 0 mM Ca2+
      + 0.5 mM EGTA; blockade reached 80% at the third 70 K+/2 Ca2+ challenge given in
      the presence of caffeine. A similar effect was obtained when, instead of
      continuous superfusion, prepulses of caffeine were applied (10 mM for 60 s). The
      blocking effects of caffeine on K+-induced secretion depended on the time of
      exposure to the drug: the longer the exposure time the greater the blockade. The
      recovery of the K+ secretory responses previously impaired by caffeine was always
      gradual and followed a staircase mode. This contrasts with the effects of
      caffeine on various parameters measuring Ca2+ entry through Ca2+ channels, which
      did not parallel its effects on K+-evoked secretion. The secretion data, however,
      are compatible with the disappearance and recovery of an intracellular Ca2+
      concentration signal triggered by K+ in single chromaffin cells loaded with fura
      2 and treated with 10 mM caffeine. Thus, contrary to previous views, the
      depression of secretion by caffeine does not seem to be associated with
      inhibition of extracellular Ca2+ entry through Ca2+ channels. These functional
      data are, rather, compatible with the view that the degree of filling of a
      caffeine-sensitive intracellular Ca2+ store might regulate the extent of
      exocytosis. When emptied, such a store might act as a sink for the external Ca2+
      entering through Ca2+ channels during cell depolarization, thus decreasing the
      intracellular Ca2+ concentration available for exocytosis.

PMID- 9142847
TI  - G proteins activate ionic conductances at multiple sites in T84 cells.
AB  - We examined the role of G proteins in activation of ionic conductances in
      isolated T84 cells during cholinergic stimulation. When cells were whole cell
      voltage clamped to the K+ equilibrium potential (E(K)) or Cl- equilibrium
      potential (E(Cl)) under standard conditions, the cholinergic agonist, carbachol,
      induced a large oscillating K+ current but only a small inward current. Addition
      of the GDP analogue, guanosine 5'-O-(2-thiodiphosphate), to pipettes blocked the
      ability of carbachol to activate the K+ current. Addition of the nonhydrolyzable
      GTP analogue, guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS), to pipettes
      stimulated large oscillating K+ and inward currents. This occurred even when Ca2+
      was absent from the bath but not when the Ca2+ chelator, ethylene glycol-bis(beta
      aminoethyl ether)-N,N,N',N'-tetraacetic acid, was added to pipettes. When all
      pipette and bath K+ was replaced with Na+ and cells were voltage clamped between
      E(Na) and E(Cl), GTPgammaS activated oscillating Na+ and Cl- currents. Finally,
      addition of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] to pipettes activated
      large oscillating K+ currents but only small inward currents. These results
      suggest that a carbachol-induced release of Ca2+ from intracellular stores is
      activated by a G protein through the phospholipase C-Ins(1,4,5)P3 signaling
      pathway. In addition, this or another G protein activates Cl- current by directly
      gating Cl- channels to increase their sensitivity to Ca2+.

PMID- 9142848
TI  - NH4Cl activates AE2 anion exchanger in Xenopus oocytes at acidic pHi.
AB  - In the course of experiments to define regulation by intracellular pH (pHi) of
      the AE2 anion exchanger expressed in Xenopus oocytes, we discovered an unexpected
      regulation of AE2 by NH4+. Intracellular acidification produced by extracellular
      acidification or produced by equimolar substitution of NaCl with sodium acetate
      each inhibited AE2 activity. In contrast, intracellular acidification by
      equimolar substitution of NaCl with NH4Cl activated AE2-associated, trans-anion
      dependent, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid-sensitive 36Cl-
      influx and efflux. Regulation by NH4+ was isoform specific, since neither
      erythroid nor kidney AE1 was activated. AE2 activation was maximal at <5 mM
      NH4Cl; was not mimicked by extracellular KCl, chloroquine, or polyamines; and was
      insensitive to amiloride, bumetanide, barium, and gadolinium. Whether NH4Cl acts
      directly on AE2 or on another target remains to be determined. Activation of AE2
      by NH4+ may serve to sustain Cl-/HCO3- exchange activity in the presence of
      acidic pH in renal medulla, colon, abscesses, and other AE2-expressing acidic
      locales exposed to elevated NH4+ concentration.

PMID- 9142849
TI  - Roles of cytoplasmic Ca2+ and intracellular Ca2+ stores in induction and
      suppression of apoptosis in S49 cells.
AB  - The Ca2+-ATPase inhibitors, thapsigargin and cyclopiazonic acid, depleted
      intracellular Ca2+ stores, induced large increases in intracellular Ca2+
      concentration, and caused apoptosis in S49 cells. Removal of extracellular Ca2+
      augmented apoptosis due to thapsigargin, indicating that depletion of Ca2+ from
      intracellular stores is responsible for apoptosis with this agent. Overexpression
      of the apoptosis suppressor, Bcl-2, inhibited apoptosis due to thapsigargin but
      did not affect thapsigargin-induced Ca2+ signaling. Dexamethasone induced
      apoptosis, diminished the size of the endoplasmic reticulum Ca2+ pool, and caused
      a small elevation of intracellular Ca2+. However, this elevation was not due to
      Ca2+ influx because the increase was similar in the presence or absence of Ca2+
      in the medium. Furthermore, in contrast to the results with thapsigargin,
      apoptosis due to dexamethasone was unchanged in a Ca2+-free medium. These results
      indicate that depletion of Ca2+ stores initiates a pathway leading to apoptosis.
      Elevations in cytoplasmic Ca2+ appears to play a lesser role than previously
      thought in the actions of Bcl-2 and glucocorticoids.

PMID- 9142850
TI  - Tissue specificity and alternative splicing of the Na+/Ca2+ exchanger isoforms
      NCX1, NCX2, and NCX3 in rat.
AB  - The gene coding for the Na+/Ca2+ exchanger NCX1 is characterized by a cluster of
      six exons (A, B, C, D, E, and F) coding for a variable region in the COOH
      terminus of the large intracellular loop of the protein. Alternative splicing of
      these exons generates multiple tissue-specific variants of NCX1. Using reverse
      transcriptase-polymerase chain reaction, we analyzed eight previously described
      and four new splicing isoforms of NCX1 in a wide variety of tissues and cells.
      Exons A and B are mutually exclusive, as shown in earlier studies, and splicing
      isoforms containing exon A are preferentially expressed in heart, brain, and
      skeletal muscle, whereas splicing variants with exon B are found in all rat
      tissues except heart. The second and third isoforms of the Na+/Ca2+ exchanger,
      NCX2 and NCX3, show a deletion of 37 amino acids in the intracellular loop
      corresponding to parts of the variable region of NCX1. We identified three
      splicing isoforms of NCX3 in brain and skeletal muscle by reverse transcriptase
      polymerase chain reaction. These splice variants are generated by including
      either of two alternative exons equivalent to the NCX1 exon A or B and by
      including or excluding a sequence equivalent to the NCX1 exon C. We did not
      detect any alternative splicing of NCX2. We examined selected tissues from
      neonatal and adult rats and found developmental regulation for NCX1 and NCX3
      splicing isoforms in skeletal muscle. Specific isoform patterns were also
      detected for NCX1 and NCX3 in cultured cortical neurons, astrocytes, and
      oligodendrocytes. We suggest a new terminology to distinguish the different
      splice variants of individual NCX isoforms.

PMID- 9142851
TI  - Protein kinase A phosphorylation and G protein regulation of type II pneumocyte
      Na+ channels in lipid bilayers.
AB  - Protein kinase A (PKA)- and G protein-mediated regulation of immunopurified adult
      rabbit alveolar epithelial type II (ATII) cell proteins that exhibit amiloride
      sensitive Na+ channel activity was studied in planar lipid bilayers and freshly
      isolated ATII cells. Addition of the catalytic subunit of PKA + ATP increased
      single channel open probability from 0.42 +/- 0.05 to 0.82 +/- 0.07 in a voltage
      independent manner, without affecting unitary conductance. This increase in open
      probability of the channels was mainly due to a decrease in the time spent by the
      channel in its closed state. The apparent inhibition constant for amiloride
      increased from 8.0 +/- 1.8 microM under control conditions to 15 +/- 3 microM
      after PKA-induced phosphorylation; that for ethylisopropylamiloride increased
      from 1.0 +/- 0.4 to 2.0 +/- 0.5 microM. Neither pertussis toxin (PTX) nor
      guanosine 5'-O-(3-thiotriphosphate) affected ATII Na+ channel activity in
      bilayers. Moreover, PTX failed to affect amiloride-inhibitable 22Na+ uptake in
      freshly isolated ATII cells. In vitro, ADP ribosylation induced by PTX revealed
      the presence of a specifically ribosylated band at 40-45 kDa in the total
      solubilized ATII cell protein fraction, but not in the immunopurified fraction.
      Moreover, the immunopurified channel was downregulated in response to guanosine
      5'-O-(3-thiotriphosphate)-mediated activation of the exogenous G alpha(i-2), but
      not G(oA), G alpha(i-1), or G alpha(i-3), protein added to the channel. This
      effect occurred only in the presence of actin. These results suggest that
      amiloride-sensitive Na+ channels in adult alveolar epithelia regulated by PKA
      mediated phosphorylation also retain the ability to be regulated by G alpha([i
      2), but not G alpha([i-1) or G alpha(i-3), protein.

PMID- 9142852
TI  - Effect of chronic hypoxia on K+ channels: regulation in human pulmonary vascular
      smooth muscle cells.
AB  - We investigated the effects of chronic hypoxia on the major outward K+ currents
      in early cultured human main pulmonary arterial smooth muscle cells (HPSMC).
      Unitary currents were measured from inside-out, outside-out, and cell-attached
      patches of HPSMC. Chronic hypoxia depolarized resting membrane potential (Em) and
      reduced the activity of a charybdotoxin (CTX)- and iberiotoxin-sensitive, Ca2+
      dependent K+ channel (KCa). The 4-aminopyridine-sensitive and CTX-insensitive
      channel or the delayed rectifier K+ channel was unaffected by chronic hypoxia.
      Chronic hypoxia caused a +33- to +53-mV right shift in voltage-dependent
      activation of K(Ca) and a decrease in K(Ca) activity at all cytosolic Ca2+
      concentrations ([Ca2+]i) in the range of 0.1-10 microM. Thus the hypoxia-induced
      decrease in K(Ca) activity was most likely due to a decrease in K(Ca) sensitivity
      to Em and [Ca2+]i. Chronic hypoxia reduced the ability of nitric oxide (NO.) and
      guanosine 3',5'-cyclic monophosphate (cGMP) to activate K(Ca). The cGMP-dependent
      protein kinase-induced activation of K(Ca) was also significantly inhibited by
      chronic hypoxia. In addition, inhibiting channel dephosphorylation with calyculin
      A caused significantly less increase in K(Ca) activity in membrane patches
      excised from chronically hypoxic HPSMC compared with normoxic controls. This
      suggests that the mechanism by which hypoxia modulates NO.-induced K(Ca)
      activation is by decreasing the NO./cGMP-mediated phosphorylation of the channel.

PMID- 9142853
TI  - Phospholipase D activity facilitates Ca2+-induced aggregation and fusion of
      complex liposomes.
AB  - Phospholipase D (PLD) activation in stimulated neutrophils results in the
      conversion of membrane phosphatidylcholine (PC) to phosphatidic acid (PA). This
      change in membrane phospholipid composition has two potentially positive effects
      on degranulation. It 1) replaces a nonfusogenic phospholipid with a fusogenic one
      and 2) increases the potential for interactions between membranes and the
      annexins. Modeling neutrophil degranulation, we examined the effect of PLD
      (Streptomyces chromofuscus) hydrolysis on the aggregation and fusion of liposomes
      in the presence and absence of annexin I. We found that PLD-mediated conversion
      of PC to PA lowered the [Ca2+] required for fusion. Annexin I increased the rate
      of fusion in the presence of PA, although it did not lower threshold [Ca2+],
      which remained above the physiological range. However, after hydrolysis by PLD,
      annexin I lowered the [Ca2+] required for aggregation by almost three orders of
      magnitude, to near physiological concentrations. These studies indicate that the
      activation of PLD and the production of PA may play a role in annexin-mediated
      membrane-membrane apposition.

PMID- 9142854
TI  - Mitochondrial permeability transition in hepatocytes induced by t-BuOOH: NAD(P)H
      and reactive oxygen species.
AB  - Tert-butyl hydroperoxide (t-BuOOH) induces the mitochondrial permeability
      transition (MPT) in hepatocytes, leading to cell death. Using confocal
      microscopy, we visualized pyridine nucleotide oxidation and reactive oxygen
      species (ROS) formation induced by t-BuOOH. Reduced mitochondrial pyridine
      nucleotides (NADH and NADPH) were imaged by autofluorescence. Mitochondrial
      membrane potential, ROS, onset of MPT, and cell death were monitored with
      tetramethylrhodamine methyl ester (TMRM), dichlorofluorescin, calcein, and
      propidium iodide, respectively. t-BuOOH rapidly oxidized mitochondrial NAD(P)H.
      Oxidation was biphasic, and the second slower phase occurred during mitochondrial
      ROS generation. Subsequently, MPT took place, mitochondria depolarized, and cells
      died. beta-Hydroxybutyrate, which reduces mitochondrial NAD+, delayed cell
      killing, but lactate, which reduces cytosolic NAD+, did not. Trifluoperazine,
      which inhibits MPT, did not block the initial oxidation of NAD(P)H but prevented
      the second phase of oxidation, partially blocked ROS formation, and preserved
      cell viability. The antioxidants, deferoxamine and diphenylphenylenediamine, also
      prevented the second phase of NAD(P)H oxidation. They also blocked ROS formation
      nearly completely and stopped cell killing. Both antioxidants also prevented the
      mitochondrial permeability transition and subsequent mitochondrial
      depolarization. In conclusion, NAD(P)H oxidation and ROS formation are critical
      events promoting MPT in oxidative injury and death of hepatocytes.

PMID- 9142855
TI  - Localization of amiloride-sensitive sodium channels in A6 cells by atomic force
      microscopy.
AB  - Atomic force microscopy (AFM) was used for high-resolution imaging of the apical
      distribution of epithelial Na+ channels in A6 renal epithelial cells. A6 cells
      grown on coverslips were labeled with antibodies generated against an amiloride
      sensitive epithelial Na+ channel complex purified from bovine renal medulla that
      had been conjugated to 8-nm colloidal gold particles before preparation for AFM.
      AFM revealed that there was a marked increase in the height of the microvilli in
      cells labeled with the anti-epithelial Na+ channel antibodies compared with
      unlabeled cells or cells labeled with rabbit nonimmune immunoglobulin G
      conjugated to colloidal gold particles. We interpret this apparent increase in
      microvillar height to be due to anti-epithelial Na+ channel antibody binding to
      the apical microvilli. These data demonstrate that epithelial Na+ channels are
      restricted to the apical microvilli in Na+-transporting renal epithelial cells.
      Furthermore, they demonstrate the applicability of using AFM for high-resolution
      imaging of the cell surface distribution of epithelial ion channels.

PMID- 9142856
TI  - Expression of CFTR in human and bovine thyroid epithelium.
AB  - The expression of cystic fibrosis transmembrane conductance regulator (CFTR) in
      the thyroid has not been documented to date, although a role for CFTR in the
      thyroid follicular epithelium is suggested both clinically, by the occurrence of
      subclinical hypothyroidism in patients with cystic fibrosis (CF), and
      physiologically, by the presence of low-conductance, adenosine 3',5'-cyclic
      monophosphate-activated Cl channels in the follicular cells. Using reverse
      transcriptase-polymerase chain reaction with nested primers derived from exons 13
      and 14 of the human CF gene, we have now documented the presence of CFTR mRNA in
      the human thyroid. Western blot analyses using six antibodies directed against
      different domains of human CFTR showed that a 165-kDa band was present in
      membrane extracts from bovine and human thyroid. This protein has the predicted
      size of mature CFTR and was not detected with preimmune serum or preadsorbed
      antiserum. By immunofluorescence and immunoperoxidase, CFTR was located in the
      follicular cells, with a diffuse, intracellular labeling pattern. Quantitative
      analysis revealed that 64% of the follicles were CFTR positive, but only 16% of
      the follicular cells were stained per follicle. The number of CFTR-positive cells
      was inversely proportional to the size of the follicle. These results 1)
      demonstrate the expression of CFTR at the mRNA and protein levels in human and
      bovine thyroid follicular cells and 2) suggest that CFTR expression could be
      instrumental in follicular enlargement.

PMID- 9142857
TI  - Cellular mechanism of aminoglycoside tolerance in long-term gentamicin treatment.
AB  - In the rat, nephrotoxicity results from uptake of gentamicin at the apical
      membrane of proximal tubule (PT) cells. However, during continuous gentamicin
      treatment, the PT epithelium has been shown to recover. The mechanism(s) of
      cellular recovery and development of tolerance remains unknown. Therefore, we
      undertook studies designed to characterize cellular adaptations that occur during
      long-term gentamicin (LTG) treatment. After 19 days of gentamicin treatment,
      electron microscopy morphological evaluation revealed cellular recovery with an
      apparent mild decrease in height and number of microvilli. Enzymatic analysis of
      LTG PT membranes showed that apical and basolateral membranes had essentially
      returned to normal. Analysis of apical membrane lipid content revealed persistent
      statistically significant (P < 0.01) elevations in phosphatidylinositol (PI). In
      vivo immunogold morphological studies and biochemical studies in LTG rats
      revealed that endocytosis of gentamicin was selectively reduced, whereas the
      markers of fluid-phase (horseradish peroxidase) and receptor-mediated (beta2
      microglobulin) endocytoses were unaffected or increased. Biochemical analysis
      showed that, although gentamicin binding to apical membranes isolated from LTG
      rats increased greater than twofold (P < 0.05) over membranes from untreated
      rats, in vivo cellular uptake, quantified with [3H]gentamicin, was reduced.
      Western blot analysis of LTG apical membranes and immunofluorescent staining of
      perfusion-fixed LTG kidneys showed no change in megalin levels or its apical
      membrane localization. These data imply that recovery of PT cells from and
      tolerance to LTG treatment involve a selective inhibition of gentamicin uptake
      across the apical membrane. They indicate that the mediators of gentamicin
      endocytosis were affected differently: PI levels increased, whereas megalin
      levels did not change. We conclude that selective inhibition of gentamicin uptake
      during LTG treatment is not affected by a reduction in PI or megalin levels. We
      postulate that trafficking of gentamicin and/or gentamicin-containing endocytic
      structures is reduced in LTG rats, allowing cells to develop tolerance to
      gentamicin.

PMID- 9142858
TI  - Loss of cytoskeletal support is not sufficient for anoxic plasma membrane
      disruption in renal cells.
AB  - The goal of this study was to determine whether anoxic membrane disruption is
      initiated by loss of cytoskeletal support in rabbit renal proximal tubules (PT).
      We specifically tested 1) whether cytoskeletal perturbation affects membrane
      integrity under normoxia, 2) whether cytoskeletal perturbation potentiates anoxic
      membrane damage, and 3) whether the membrane protection by glycine depends on
      cytoskeletal integrity. Cytoskeletal perturbation was achieved with 10 microM
      cytochalasin D (CD) because it selectively disturbs F-actin organization and has
      similar effects as anoxia on the cytoskeleton of PT. During normoxia, CD caused
      decreased basal F-actin content, microvillar breakdown, and membrane-cytoskeleton
      dissociation, as revealed by the use of laser tweezers. However, membrane
      integrity was not altered by CD, as monitored by lactate dehydrogenase release.
      CD pretreatment of PT did not potentiate anoxic membrane damage. Finally, plasma
      membrane protection by glycine during anoxia remained in CD-pretreated PT despite
      loss of cytoskeletal support. These results demonstrate that loss of cytoskeletal
      support is not sufficient for anoxic plasma membrane disruption.

PMID- 9142859
TI  - Leukotriene B4 costimulates 5-lipoxygenase activity in neutrophils via increased
      5-lipoxygenase translocation.
AB  - The goal of this investigation was to assess the effect of leukotriene B4 (LTB4)
      on 5-lipoxygenase activity and to examine the possible mechanisms of this effect.
      Exogenous LTB4 significantly increased the release of endogenous LTB4 from A
      23187-stimulated neutrophils. The 5-lipoxygenase product release from A-23187
      stimulated neutrophils decreased in the presence of an LTB4 receptor antagonist,
      suggesting that LTB4 has a receptor-mediated, autocrine effect on 5-lipoxygenase
      activity. Neutrophil 5-lipoxygenase activity increased significantly as cell
      density increased. In the presence of exogenous LTB4, no significant change in
      [14C]arachidonic acid release from neutrophils was observed. Exogenous LTB4
      increased the amount of immunoreactive 5-lipoxygenase protein detected in the
      nuclear fraction of disrupted cells. LTB4 receptor antagonism decreased the
      amount of immunoreactive 5-lipoxygenase detected in the nuclear fraction. Thus
      LTB4 exerts an autocrine, receptor-mediated, costimulatory effect on 5
      lipoxygenase activity. This feedback appears to have biological significance and
      involves enhanced 5-lipoxygenase translocation to the nuclear membrane.

PMID- 9142860
TI  - Cloning and widespread distribution of the rat rod-type cyclic nucleotide-gated
      cation channel.
AB  - We used Northern blot analysis, ribonuclease protection assay (RPA), reverse
      transcriptase-polymerase chain reaction, and in situ hybridization to investigate
      the hypothesis that the CNG1 isoform of the cyclic nucleotide-gated nonselective
      cation channel may be widely distributed in tissues of the rat. A cDNA encoding
      the CNG1 isoform was isolated from rat eye and human retina, and partial
      sequences were isolated from rat pineal gland and human kidney. Northern blot
      analysis revealed a 3.1-kilobase (kb) CNG1 transcript in rat eye, pineal gland,
      pituitary, adrenal gland, and spleen, and a larger transcript of 3.5 kb was found
      in testis. RPA confirmed the identity of CNG1 mRNA in rat eye, lung, spleen, and
      brain. Polymerase chain reaction-based detection of the mRNA for CNG1 indicates
      that the channel is expressed in lower abundance in many other tissues, including
      thymus, skeletal muscle, heart, and parathyroid gland. The cellular distribution
      of CNG1 was further studied by in situ hybridization, which demonstrated
      expression of mRNA in lung, thymus, pineal gland, hippocampus, cerebellum, and
      cerebral cortex but not in heart or kidney.

PMID- 9142861
TI  - Mitochondrial biogenesis during cellular differentiation.
AB  - Mitochondrial biogenesis was studied during differentiation of two immortalized
      cell lines (C2C12, 3T3) with enzyme measurements, Northern blots, and
      quantitative ultrastructure. Citrate synthase, isocitrate dehydrogenase, and 3
      hydroxyacyl-CoA dehydrogenase (nuclear encoded, mitochondrial matrix location)
      showed linear, four- to sixfold increases in enzymatic activity in C2C12 cells
      but increased exponentially in 3T3 cells. Cytochrome oxidase and NADH
      dehydrogenase (nuclear and mitochondrial encoded, cristae location) increased to
      a lesser extent and with a pattern dissimilar to the first group. Northern blots
      and activity of succinate dehydrogenase (cristae location but entirely nuclear
      encoded) suggested the groupings were based on location of the genes rather than
      the mature enzyme. However, quantitative electron microscopy and comparisons with
      adult tissue suggested that mitochondrial ultrastructure can influence the change
      in cristae enzymes. Cristae surface area per unit mitochondrial volume and per
      unit cell volume increased much less than did cristae enzymes. Available space on
      the inner membrane may become limiting and account for some aspects of the
      pattern of change in electron transport enzymes during differentiation.

PMID- 9142862
TI  - Cytokine control of PMN phagocytosis: regulatory effects of hypoxemia and
      hypoxemia-reoxygenation.
AB  - We investigated the effects of hypoxemia and hypoxemia-reoxygenation (H/R) on
      interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), or IL-1beta
      stimulation of whole blood polymorphonuclear leukocyte (PMN) phagocytosis and
      bactericidal activity. Whole blood PMN were rendered hypoxemic (venous PO2 < 15
      mmHg), normoxic (venous PO2 60-80 mmHg), or reoxygenated after hypoxemia (H/ R =
      venous PO2 150-200 mmHg) and were incubated with IL-8, TNF-alpha, or IL-1beta
      before sequential addition of serum-opsonized fluorescent microspheres and
      fluorescein isothiocyanate-conjugated mouse anti-human CD64, CD32w, CD16, CD35,
      or CD11b/CD18. Concomitant two-color flow cytometric analyses were then performed
      measuring mean channel fluorescence and the percentage of PMN positive for
      phagocytosis, with simultaneous subset receptor analysis on populations of PMN
      that exceeded control levels of phagocytosis. During hypoxemia, whole blood PMN
      phagocytosis in the presence of IL-8, TNF-alpha, or IL-1beta was increased
      compared with normoxia. Northern blot analyses revealed an increase in steady
      state mRNA levels for CD32w during hypoxemia + IL-8 and CD64 during hypoxemia +
      IL-1beta. During reoxygenation, both whole blood PMN phagocytosis and
      bactericidal activity were reduced in the presence of IL-8, TNF-alpha, or IL
      1beta, and in subsets of PMN with reduced phagocytosis H/R reduced CD64, CD32w,
      CD16, CD35, and CD11b/CD18 expression in the presence of each cytokine. Northern
      blot analyses revealed that H/R reduced mRNA levels for opsonic receptors
      primarily for IL-1beta-stimulated PMN. These results demonstrate a direct
      regulatory effect of hypoxemia and H/R on whole blood PMN phagocytosis, receptor
      expression, and steady-state mRNA levels of both Fc(gamma) and complement
      receptors.

PMID- 9142863
TI  - Evidence for a calmodulin-dependent phospholipase A2 that inhibits Na-K-ATPase.
AB  - We tested whether calnaktin, a proposed Ca/calmodulin (CaM)-dependent protein
      that inhibits the Na-K-ATPase, was a kinase, a phosphatase, a phospholipase A2
      (PLA2), or a Ca-dependent protease. Human red blood cell membranes were extracted
      to remove associated calmodulin but to retain the proposed endogenous calnaktin.
      Exclusively cytoplasmic proteins and cofactors were presumably absent. In these
      membranes, free Ca inhibited the Na-K-ATPase with an inhibition constant (K[i])
      of > or = 9 microM at a Na concentration of 18 mM. Addition of 100 nM CaM
      decreased the Ki to < 2 microM and increased the percent inhibition at 2 microM
      free Ca from 18 +/- 1 to 68 +/- 2%. The inhibitory effect of Ca/CaM was
      reversible, indicating that calnaktin is not a protease. Neither staurosporine
      (500 nM), 1-(N,O-bis[5-isoquinolinesulfonyl]-N-methyl-L-tyrosyl)-4-phenylpipera
      zin e (5 microM), nor genistein (100 microM) diminished Ca/CaM inhibition of the
      Na-K-ATPase. Thus there is no evidence that this protein is a kinase. Likewise,
      the phosphatase inhibitors microcystin (1 microM) and okadaic acid (10 microM)
      had no effect. PLA2 inhibitors arachidonyl trifluoromethyl ketone (AACOCF3),
      parabromophenacyl bromide (pBPB), and quinacrine all abolished Ca/CaM inhibition
      of the Na-K-ATPase. Ca/CaM also increased PLA2 activity, as reflected by an
      increase in the slope of fluorescence signal of 10-pyrene phosphatidylcholine, a
      substrate for PLA2. This Ca/CaM-induced change in slope was inhibited by both
      pBPB and AACOCF3. These data suggest that human red cell membranes contain a form
      of PLA2 that is activated by Ca/CaM and that this enzyme may mediate Ca/CaM
      inhibition of the Na-K-ATPase.

PMID- 9142864
TI  - Modes of operation of an electroneutral Na+/Li+ countertransport in human skin
      fibroblasts.
AB  - An elevated activity of erythrocyte Na+/Li+ countertransport (SLC) is an
      intermediate phenotype of human essential hypertension, but cells other than
      erythrocytes have not been studied. Therefore, we have examined several transport
      modes of Na+/Li+ exchange in human skin fibroblasts. External Na+-stimulated Li+
      efflux was 152 +/- 31 (SE) nmol x mg protein(-1) x min(-1) (n = 8). At
      intracellular pH 7.3, intracellular Na+-stimulated Li+ influx, intracellular Li+
      stimulated Na+ influx, and external Li+-stimulated Na+ efflux were very similar,
      indicating the presence of a tightly coupled 1:1 SLC. This pathway was not
      affected by 5-(N,N-dimethyl)-amiloride and changes in the membrane potential, but
      phloretin and intracellular acidification (intracellular pH 6.8) were markedly
      inhibitory. Kinetic analyses of the external Na+ site also compared with SLC,
      although the internal site appeared to show a low affinity for Li+. We conclude
      that an SLC pathway similar to that in human erythrocytes is expressed in human
      skin fibroblasts.

PMID- 9142865
TI  - Role of extracellular signal-regulated kinase and PKC alpha in cytosolic PLA2
      activation by bradykinin in MDCK-D1 cells.
AB  - The actions of bradykinin (BK) in Madin-Darby canine kidney (MDCK) and other cell
      types involve formation of arachidonic acid (AA) and AA products by as-yet
      undefined mechanisms. We found that BK promoted AA release and an increase in
      phospholipase A2 (PLA2) activity in subsequently prepared MDCK-D1 cell lysates,
      both of which were Ca2+ dependent and were inhibited by the 85-kDa cytosolic PLA2
      (cPLA2) inhibitor arachidonyl trifluoromethyl ketone. In addition, BK treatment
      of cells led to increased PLA2 activity of cPLA2 immunoprecipitated from lysates.
      Thus BK receptors mediate AA release via cPLA2 in MDCK-D1 cells. The BK-promoted
      increase of cPLA2 activity was reversed by treatment of cell lysates with potato
      acid phosphatase, implying that phosphorylation underlies the activation of
      cPLA2. However, extracellular signal-regulated kinase (ERK) appeared not to be
      responsible for this phosphorylation, because treatment of cells with BK (in
      contrast with the results obtained with epinephrine and phorbol ester) caused
      neither enzyme activation nor phosphorylation (as judged by molecular mass shift)
      of this kinase. Although the alpha isoform of protein kinase C (PKC alpha) is
      responsible for AA release promoted by phorbol ester treatment of MDCK-D1 cells
      (C. Godson, K.S. Bell, and P.A. Insel. [corrected] J. Biol. Chem. 268: 11946
      11950, 1993), neither treatment of cells with the PKC alpha-selective inhibitor
      GF109203X nor transfection of cells with PKC alpha antisense cDNA altered BK
      mediated AA release. We conclude that PKC alpha is unlikely to play an important
      role in the regulation of cPLA2 by BK receptors in MDCK-D1 cells. The tyrosine
      kinase inhibitor herbimycin A, on the other hand, inhibited both BK-promoted AA
      release in intact cells and cPLA2 activation in cell lysates, suggesting the
      involvement of tyrosine kinase in the regulation of this lipase by BK receptors.
      Taken together, these data suggest that BK receptors in MDCK-D1 cells regulate
      cPLA2 via phosphorylation mediated by kinases other than ERK and PKC alpha.

PMID- 9142866
TI  - Changes in P2Y1 nucleotide receptor activity during the development of rat
      salivary glands.
AB  - Experiments that used dispersed salivary gland cells from 1-day-old rats
      indicated the presence of the P2Y nucleotide receptor subtype, P2Y1, based on the
      agonist potency profile for mobilization of intracellular free Ca2+ [2-methylthio
      ATP > ADP > adenosine 5'-O-(2-thiodiphosphate) > ATP, with UTP ineffective] and
      sequence analysis of reverse transcription-polymerase chain reaction (RT-PCR)
      products obtained with P2Y1 receptor-specific primers. P2Y1 receptor activity
      appears to be developmentally regulated, since Ca2+ mobilization in response to
      the P2Y1-selective agonist, 2-methylthio-ATP, decreased as animal age increased,
      with the maximal response of 129 +/- 23 nM obtained in 1-day-old animals,
      decreasing to 30 +/- 3 nM in 4-wk-old animals. However, the abundance of P2Y1
      receptor mRNA, assessed by semiquantitative RT-PCR, did not change over this time
      period, suggesting that receptor activity is regulated by some mechanism other
      than changes in steady-state levels of P2Y1 receptor mRNA. These findings
      indicate that functional P2Y1 nucleotide receptors are expressed in immature
      salivary glands and that receptor activity decreases as the glands mature,
      suggesting that P2Y1 receptors may have an important role during salivary gland
      development.

PMID- 9142867
TI  - Telokin expression in A10 smooth muscle cells requires serum response factor.
AB  - Telokin transcription is initiated from a smooth muscle-specific promoter located
      in an intron of the smooth muscle myosin light chain kinase gene. We have
      previously identified a 310-base pair fragment of the promoter that mediates A10
      smooth muscle cell-specific expression of telokin. In the current study, telokin
      luciferase reporter gene assays in A10 cells and REF52 nonmuscle cells revealed
      that the promoter region between -81 and +80 contains the regulatory elements
      required to mediate the in vitro cell specificity of the promoter. Several
      positive-acting elements, including an E box, myocyte enhancer factor 2 (MEF2)
      TATA box, and CArG-serum response element, were identified within this region.
      Telokin transcription in A10 smooth muscle cells requires all three transcription
      initiation sites and an AT-rich sequence between -71 and -62 that includes a TATA
      box. MEF2 interacts with the AT-rich region with low affinity; however, MEF2
      binding is not required for transcriptional activity in A10 cells. Binding of
      serum response factor (SRF) to a CArG element proximal to the TATA sequence is
      also critical for high levels of transcription in A10 cells. Together these data
      suggest that an AT-rich motif, acting in concert with SRF and an unusual
      transcription initiation mechanism, is required for the cell-specific expression
      of the telokin promoter in A10 smooth muscle cells.

PMID- 9142868
TI  - Measurement of changes in cell volume based on fluorescence quenching.
AB  - The intracellular fluorescence of 6-methoxy-N-(3-sulfopropyl)-quinolinium (SPQ),
      a Cl(-) -sensitive fluorescent dye, is quenched by intracellular organic anions
      and proteins of unknown identity. The concentration of these intracellular
      quenchers (ICQs), however, is dependent on cell volume. In the absence of Cl-,
      changes in the observed SPQ fluorescence may therefore reflect changes in cell
      volume. This concept has been applied to determine relative changes in cell
      volume of cultured corneal endothelium in response to anisosmotic shocks, using
      NO3- as the Cl- substituent. SPQ fluorescence increased with decreasing
      osmolarity and vice versa. A 20 mosM hypertonic shock was needed to detect a
      change in SPQ fluorescence with a signal-to-noise ratio of >25. Assuming dynamic
      quenching by ICQs, we applied an extension of the Stern-Volmer equation to
      develop a simple relationship between the measured SPQ fluorescence and relative
      changes in cell volume. For large hyposmotic shocks, regulatory volume decrease
      (RVD) was observed. The rate of RVD could be enhanced by exposure to 0.5 microM
      gramicidin in low-Na+ Ringer solution (i.e., K+-NO3- efflux), indicating that K+
      conductance is rate limiting for RVD. These results demonstrate the principle of
      using fluorescence quenching to measure changes in cell volume in real time.
      Because SPQ is sensitive to Cl-, its usefulness as a quenching probe is limited.
      However, a structure-activity study can be expected to yield useful Cl(-)
      insensitive analogs.

PMID- 9142869
TI  - Central opioid receptors mediate glucoprivic inhibition of pituitary LH
      secretion.
AB  - The present studies investigated the significance of glucoprivic metabolic
      signals, particularly those of central origin, to the regulation of pituitary
      luteinizing hormone (LH). Groups of gonadectomized (GDX) adult male rats were
      treated with 2-deoxy-D-glucose (2-DG), an inhibitor of glycolysis, by either
      intravenous (50, 100, or 200 mg/kg) or intracerebroventricular (5, 20, or 100
      microg/rat) administration. Systemic drug treatment caused a significant decrease
      in mean plasma LH levels compared with saline-treated controls.
      Intracerebroventricular administration of 2-DG was also efficacious in
      suppressing circulating LH; animals treated with either of the two highest doses
      of the drug exhibited a significant reduction in plasma LH. In vitro studies
      examined direct effects of 2-DG on pituitary gonadotrope secretory activity.
      Exposure of anterior pituitary tissue to 2-DG during short-term perfusion had no
      significant impact upon either basal or gonadotropin-releasing hormone-stimulated
      LH release. Finally, groups of GDX rats were pretreated by
      intracerebroventricular administration of either the nonselective opioid receptor
      antagonist, naltrexone, or the selective mu-opioid receptor antagonist, beta
      funaltrexamine (beta-FNA), before intravenous injection of 2-DG. Both receptor
      antagonists were observed to attenuate the suppressive effects of 2-DG on
      circulating LH in these animals. In summary, treatment of GDX rats with the
      glucose antimetabolite, 2-DG, decreased plasma LH, suggesting that metabolic
      signaling of cellular glucose oxidation is of physiological importance to the
      regulation of pituitary hormone secretion. Findings that plasma LH was diminished
      in animals treated intracerebroventricularly with 2-DG implicate central
      glucoprivic receptors in neuroendocrine mechanisms governing the reproductive
      endocrine axis. Attenuation of 2-DG-induced decreases in circulating LH by opioid
      receptor antagonists suggests that these receptors, particularly the mu-subtype,
      mediate central effects of glucoprivation on circulating LH.

PMID- 9142870
TI  - Glucose-fatty acid interactions in prepubertal and pubertal children: effects of
      lipid infusion.
AB  - This investigation examined whether puberty differs from prepuberty in regard to
      the effects of increased free fatty acid (FFA) on in vivo glucose metabolism.
      Nine prepubertal and 13 pubertal healthy children were studied. Each subject was
      studied twice, once with 0.9% sodium chloride solution (control study) and once
      with 20% Intralipid infusion in the basal state and during a 3-h hyperinsulinemic
      euglycemic clamp, with [6,6-2H2]glucose tracer. During control studies,
      prepubertal children had lower basal fat oxidation and higher insulin-mediated
      glucose disposal than pubertal adolescents. During Intralipid infusion, basal
      glucose uptake increased in prepubertal children but did not change in pubertal
      adolescents. Insulin-stimulated whole body glucose disposal did not change in
      prepubertal children (control 77.6 +/- 8.9, Intralipid 84.5 +/- 13.3 micromol x
      kg(-1) x min(-1)) but decreased in pubertal adolescents (control 55.0 +/- 3.6,
      Intralipid 46.7 +/- 3.4 micromol x kg(-1) x min(-1), P = 0.01) despite comparable
      decrements in glucose oxidaion. We conclude that in prepubertal children lipids
      exert effects in the basal state by stimulating hepatic glucose production and
      glucose disposal, whereas in pubertal adolescents they induce peripheral tissue
      insulin resistance by decreasing insulin-stimulated glucose uptake. This
      differential response could be due to developmental-maturational changes in
      tissue sensitivity and/or specificity to the glucose-FFA interaction.

PMID- 9142871
TI  - Interaction of exercise, insulin, and hypoglycemia studied using euglycemic and
      hypoglycemic insulin clamps.
AB  - Hyperinsulinemic euglycemic and hypoglycemic clamps were used to study the
      interaction of exercise, insulin, and hypoglycemia at rest and during exercise in
      the dog. Sampling (artery and portal, hepatic, and iliac veins) and infusion
      (vena cava) catheters and a flow probe (external iliac artery) were implanted
      surgically >16 days before study. After an 18-h fast and an 80-min tracer
      equilibration period, dogs were studied in the basal state (t = -40 to 0 min) and
      during a moderate treadmill exercise (t = 0-150 min) period or an equivalent
      duration sedentary period. Insulin was infused at 1 mU x kg(-1) x min(-1) from t
      = 0-150 min. In one group of sedentary (n = 7) and one group of exercised (n = 6)
      dogs, glucose was clamped at basal during the insulin infusion. In another group
      of sedentary (n = 6) and another group of exercised (n = 6) dogs, arterial
      glucose was clamped at hypoglycemic levels (approximately 65 mg/dl) during the
      insulin infusion. Arteriovenous difference and isotopic ([3-(3)H]glucose, [U
      (14)C]glucose) techniques were used to assess glucose metabolism. Insulin levels
      were approximately 40 microU/ml in all groups. Data show that 1)
      counterregulatory hormone (glucagon, catecholamines, and cortisol) responses to
      exercise and hypoglycemia combined are synergistically higher than the response
      to either stimulus alone; 2) exercise-induced increases in insulin action are
      negated during hypoglycemia by the counterregulatory response; 3) decreased need
      for exogenous glucose during hypoglycemic compared with euglycemic exercise is
      due to stimulation of endogenous glucose production, which accounts for
      approximately 30% of the decrease, and reduction of glucose utilization, which
      accounts for approximately 70%; and 4) insulin-stimulated nonoxidative glucose
      metabolism is unaffected by exercise or hypoglycemia, whereas insulin-stimulated
      oxidative glucose metabolism is selectively increased by exercise and decreased
      by hypoglycemia. In conclusion, the marked rise in insulin action during exercise
      is matched, under insulin-induced hypoglycemic conditions, by an equally profound
      increase in counterregulation. The effectiveness of the potent insulin
      counterregulatory response may be important in decreasing the magnitude and
      frequency of exercise-induced hypoglycemia.

PMID- 9142872
TI  - Glucose regulation of islet amyloid polypeptide gene expression in rat pancreatic
      islets.
AB  - Intracellular pathways by which glucose regulates islet amyloid polypeptide
      (IAPP) gene expression in pancreatic islets were studied. IAPP mRNA levels were
      threefold higher in islets cultured with 16.7 mM glucose compared with control
      (5.5 mM glucose). Mannose and amino acids but not 2-deoxyglucose or 6
      deoxyglucose mimicked the effect of glucose. Mannoheptulose (a glycolysis
      inhibitor) and verapamil and diazoxide (which affect calcium signaling pathway)
      abolished the difference in islet IAPP mRNA content between high and low glucose.
      At low glucose, IAPP mRNA levels were increased 1.9-fold in islets treated with
      forskolin or dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) but not with
      12-O-tetradecanoylphorbol 13-acetate. Insulin mRNA levels were 1.6-fold higher in
      islets cultured at high glucose than controls; glucose metabolism was required,
      whereas no effects of cAMP or diazoxide were observed. IAPP and insulin were
      cosecreted into the media. We conclude that glucose regulation of IAPP mRNA
      abundance requires intracellular metabolism of the hexose and that calcium may
      serve as a mediator of this effect; cAMP but not protein kinase C possibly
      participates in this regulation.

PMID- 9142873
TI  - Long- and medium-chain triglycerides during parenteral nutrition in critically
      ill patients.
AB  - Due to their special metabolic pathway, medium-chain triglycerides (MCT) have
      been claimed to be oxidized more extensively, compared with long-chain
      triglycerides (LCT), when administered as a parenteral nutritional support. This
      enhanced lipid oxidation rate of MCT emulsions could be particularly disclosed in
      hyperglycemic and hyperinsulinemic conditions. In an attempt to further elucidate
      this question, we measured substrate oxidation rates in critically ill patients
      liable to experience such metabolic conditions, that is to say postoperative
      patients after esophageal resection receiving 1.5 times their measured energy
      expenditure (n = 12) or after liver transplantation (n = 8). These patients
      received either LCT or MCT-LCT emulsions. The metabolic measurements were
      performed simultaneously by two methods, namely indirect calorimetry and isotopic
      methods based on natural abundance of nutrients. Although both groups of patients
      were hyperglycemic and hyperinsulinemic, the measured carbohydrate and lipid
      oxidation rates were not different with whatever type of lipid was administered.
      The MCT-LCT emulsions did not offer clear-cut advantages over LCT emulsions in
      critically ill patients when lipid energetic fate was considered.

PMID- 9142874
TI  - Glucoregulation during progressive starvation in late pregnancy in the rat.
AB  - The response of glucose utilization (transport and phosphorylation) by individual
      skeletal muscles to progressive starvation in late pregnancy in the rat was
      investigated in relation to changes in whole body glucose turnover. Compared with
      insulin-stimulated values, the decline in muscle glucose utilization evoked by
      short-term (6-h) starvation was about twofold greater in pregnancy. Suppression
      of glucose utilization by slow-twitch muscles was observed as the starvation
      period was extended from 6 to 24 h only in unmated rats. Extending starvation to
      24 h did not further reduce glucose utilization by fast-twitch skeletal muscles
      in either group. Suppression of whole body glucose disposal was observed between
      6 and 24 h of starvation in unmated, but not pregnant, rats. The results
      demonstrate that metabolic adaptation of almost complete suppression of glucose
      utilization by slow-twitch muscle, normally elicited only by prolonged (24-h)
      starvation, is already established after acute (6-h) starvation in late
      pregnancy. The present study supports the concept of "accelerated starvation" in
      late pregnancy with respect to muscle glucose utilization after short-term food
      withdrawal but demonstrates that further glucose conservation cannot be achieved
      after more prolonged starvation.

PMID- 9142875
TI  - Gender-dependent effects of exercise training on serum leptin levels in humans.
AB  - Leptin, the product of the ob gene, is elevated in obese humans and appears to be
      closely related to body fat content. The purpose of the present investigation was
      to determine the effect of aerobic exercise training on systemic leptin levels in
      humans. Eighteen sedentary middle-aged men (n = 9) and women (n = 9) who did not
      differ in aerobic capacity (29.4 +/- 1.2 vs. 27.5 +/- 1.2 ml x kg(-1) x min(-1))
      or insulin sensitivity index (3.41 +/- 1.12 vs. 4.88 +/- 0.55) were studied. Fat
      mass was significantly lower in females vs. males (21.83 +/- 2.25 vs. 26.99 +/-
      2.37 kg, P < 0.05). Despite this, fasting serum leptin was significantly higher
      in the females vs. males (18.27 +/- 2.55 vs. 9.88 +/- 1.26 ng/ml, P < 0.05).
      Serum leptin concentration decreased 17.5% in females (P < 0.05) after 12 wk of
      aerobic exercise training (4 day/wk, 30-45 min/day) but was not significantly
      reduced in males. Fat mass was not altered after training in either group. In
      contrast, both aerobic capacity (+13% males, +9.1% females) and insulin
      sensitivity (+35% males, +82% females) were significantly improved subsequent to
      training. These data suggest that 1) women have higher circulating leptin
      concentrations despite lower fat mass and 2) exercise training appears to have a
      greater effect on systemic leptin levels in females than in males.

PMID- 9142876
TI  - Brain of the conscious dog is sensitive to physiological changes in circulating
      insulin.
AB  - The aim of this study was to determine whether a selective, physiologically
      relevant increase in blood-borne insulin perfusing the brain has an impact on the
      counterregulatory response to hypoglycemia. Experiments were carried out on 12
      conscious 18-h-fasted dogs. Insulin was infused (1 mU x kg(-1) x min(-1)) in
      separate, randomized studies into a peripheral vein (n = 6) or both carotid and
      vertebral arteries (n = 6). This resulted in equivalent systemic insulinemia (38
      +/- 2 vs. 35 +/- 5 microU/ml) but differing head insulin levels (38 +/- 2
      microU/ml during peripheral infusion and an estimated 90 microU/ml during head
      insulin infusion). Glucose was infused during peripheral insulin infusion to
      equate the level of hypoglycemia (58 +/- 2 mg/dl) to that obtained during head
      insulin infusion (57 +/- 2 mg/dl). Despite equivalent peripheral insulin levels
      and hypoglycemia, incremental area under the curve responses for epinephrine,
      glucagon and cortisol were increased during head insulin infusion (P < 0.05). Net
      hepatic glucose output, gluconeogenesis, and lipolysis were increased 50-100% (P
      < 0.05) during head compared with peripheral insulin infusion. We conclude that
      during hypoglycemia in the conscious dog 1) physiologically relevant increases of
      blood-borne insulin to the head can amplify neuroendocrine and metabolic
      counterregulatory responses and 2) glucagon secretion can be regulated, in part,
      by neural efferent activity.

PMID- 9142877
TI  - Insulin stimulation of human adipocytes activates the kinase of only a fraction
      of the insulin receptors.
AB  - The degree of insulin receptor kinase activation by in situ stimulation was
      studied in isolated human adipocytes. Although maximal in situ stimulation
      increased the kinase activity approximately 10-fold, this activity could again be
      doubled by subsequent activation in a cell-free system. To investigate how in
      situ stimulation resulted in incomplete activation, receptors binding or not
      binding to anti-phosphotyrosine antibody (alpha-PY) were studied separately. Even
      after maximal insulin stimulation of the cells, approximately 50% of the
      receptors did not bind to alpha-PY and had low kinase activity. In the cell-free
      system, however, these receptors reached activity levels similar to the other
      receptors, suggesting that they were intact and that factors in their cellular
      environment had prevented their activation. The activity of the alpha-PY-binding
      receptors could only be slightly increased in the cell-free system, suggesting
      that almost complete activation had been attained in situ. In situ stimulation
      with increasing insulin concentrations increased the number of activated
      receptors rather than their individual activity. We conclude that factors in the
      in situ environment prevent insulin activation of approximately 50% of the
      insulin receptors in human adipocytes and might therefore be important regulators
      of insulin signaling.

PMID- 9142878
TI  - Influence of protein intake on whole body and splanchnic leucine kinetics in
      humans.
AB  - The influence of the protein content of the meal on protein turnover was
      investigated in the splanchnic bed and in the remaining parts of the body in
      humans. Two groups of five subjects consumed every 20 min a liquid formula
      providing either 1.5 g protein x kg(-1) x day(-1) (P) or no protein (PF). L-[1
      (13)C]leucine and L-[5,5,5-(2)H3]leucine were administered by vein and gut,
      respectively. An open two-pool model was developed to calculate leucine kinetics
      in both compartments, with the assumption that the enrichment of the tracers
      incorporated into very low density lipoprotein apolipoprotein B100 at isotopic
      steady state could reflect the leucine labeling in the splanchnic region.
      Nonsplanchnic uptake and release of leucine were not significantly different in
      the two groups. Within the splanchnic area, leucine uptake was 2.1 times higher
      in the P than in the PF group (P < 0.01), whereas leucine release was reduced but
      not significantly (-19%) in the P group compared with the PF group. Moreover,
      data derived from this model showed that protein intake induced an increase in
      whole body protein synthesis and no change in whole body protein breakdown.
      Albumin synthesis, as well as its contribution to whole body protein synthesis,
      was significantly enhanced by protein intake.

PMID- 9142879
TI  - Amino acids suppress proteolysis independent of insulin throughout the neonatal
      period.
AB  - To determine how increased amino acid availability alters rates of whole body
      proteolysis and the irreversible catabolism of the essential amino acids leucine
      and phenylalanine throughout the neonatal period, leucine and phenylalanine
      kinetics were measured under basal conditions and in response to intravenous
      amino acids in two separate groups of healthy, full-term newborns (at 3 days and
      3 wk of age). The endogenous rates of appearance of leucine and phenylalanine
      (reflecting proteolysis) were suppressed equally in both groups and in a dose
      dependent fashion (by approximately 10% with 1.2 g x kg(-1) x day(-1) and by
      approximately 20% with 2.4 g x kg(-1) x day(-1)) in response to intravenous amino
      acid delivery. Insulin concentrations remained unchanged from basal values during
      amino acid administration. The irreversible catabolism of leucine and
      phenylalanine increased in a stepwise fashion in response to intravenous amino
      acids; again, no differences were observed between the two groups. This study
      clearly demonstrates that the capacity to acutely increase rates of leucine
      oxidation and phenylalanine hydroxylation is fully present early in the neonatal
      period in normal newborns. Furthermore, these data suggest that amino acid
      availability is a primary regulator of proteolysis in normal newborns throughout
      the neonatal period.

PMID- 9142880
TI  - Insulin stimulates cell surface aminopeptidase activity toward vasopressin in
      adipocytes.
AB  - We previously discovered that insulin stimulates the marked translocation of a
      novel membrane aminopeptidase, designated vp165 for vesicle protein of 165 kDa,
      to the cell surface in adipocytes. To examine the hypothesis that this enzyme
      acts on peptide hormones, we assessed the relative affinity of the enzyme for 22
      peptide hormones by measuring the inhibitory effect of each on the hydrolysis of
      a fluorogenic substrate, and we directly assayed the cleavage of four of these.
      Angiotensin III, angiotensin IV, and Lys-bradykinin bound to the enzyme with half
      saturation constants between 20 and 600 nM and were cleaved by vp165. Vasopressin
      bound with lower affinity but at saturation was cleaved more rapidly.
      Subsequently, the effect of insulin on the rates of cleavage of 125I-labeled
      vasopressin by intact 3T3-L1 and rat adipocytes was determined. With both cell
      types, vasopressin cleavage was stimulated approximately threefold. These
      findings indicate that a physiological role for vp165 may be the processing of
      peptide hormones and that insulin could enhance the cleavage of extracellular
      substrates by eliciting the translocation of vp165 to the cell surface.

PMID- 9142881
TI  - Insulin receptor mRNA splicing and altered metabolic control in aged and mildly
      insulin-deficient rats.
AB  - Using reverse transcription-competitive polymerase chain reaction, we measured
      the abundance of the mRNAs encoding the two spliced isoforms of insulin receptor
      in aged and mildly insulin-deficient rats. Twelve-month-old rats were
      characterized by peripheral insulin resistance and decreased glucose tolerance.
      Mild insulin deficiency, obtained by neonatal streptozotocin treatment, was
      associated with glucose intolerance due to reduced glucose-stimulated insulin
      response. Both models were associated with a decrease in the relative abundance
      of the mRNA with exon 11 in liver, heart, adipose tissue, and tibialis muscle,
      whereas a slight increase was seen in the extensor digitorum longus and no change
      in the soleus muscle. In the three muscles, the expression of the form without
      exon 11 largely predominated (>90%). In heart and adipose tissue, the two
      isoforms were expressed at a similar level in control rats. In both tissues, the
      form without exon 11 increased in streptozotocin-treated rats, whereas the
      absolute level of the form with exon 11 decreased in old rats. Although a
      decreased level of the variant with exon 11 correlated with insulin resistance of
      whole body glucose uptake, our results indicated that changes in the expression
      of the insulin receptor variants were secondary events and thus not the cause of
      the insulin resistance in old and mildly insulin-deficient rats.

PMID- 9142882
TI  - Nongenomic effects of aldosterone on intracellular calcium in porcine endothelial
      cells.
AB  - Rapid in vitro effects of aldosterone on intracellular electrolytes, cell volume,
      and the sodium-proton antiport have been described in human mononuclear
      leukocytes and vascular smooth muscle cells. In the present study, we demonstrate
      rapid aldosterone effects on free intracellular calcium as determined by fura 2
      fluorometry in single porcine endothelial cells. After addition of 100 nmol/l
      aldosterone, cells respond with a sustained rise in free intracellular calcium by
      approximately 50% of initial levels within 1-5 min. Elevations are predominantly
      seen in the subplasmalemmal space. Effective half-maximal concentration values
      for aldosterone are approximately 1 pmol/l and for cortisol approximately 1
      nmol/l. These effects are blunted in calcium-free medium and absent after
      pretreatment by thapsigargine. They remain unchanged by a >1,000-fold excess of
      spironolactone. These findings indicate the existence of a nongenomic pathway for
      aldosterone action in porcine endothelial cells and may be related to known rapid
      cardiovascular effects of aldosterone in vivo mediated through the baroreceptor
      reflex.

PMID- 9142883
TI  - Steady-state and non-steady-state measurements of plasma glutamine turnover in
      humans.
AB  - To compare steady-state glutamine turnover using nitrogen, carbon, and hydrogen
      tracers and to test the validity of monocompartmental equations to determine
      plasma glutamine turnover under non-steady-state conditions, we infused 10 normal
      postabsorptive volunteers simultaneously with [3,4-3H]glutamine, [2
      15N]glutamine, and [U-14C]glutamine for 4 h to isotopic steady state. Eight of
      the ten subjects were subsequently infused in a stepwise fashion with exogenous
      glutamine. Plasma glutamine enrichment and specific activities fit a
      monoexponential model well (r = 0.89, 0.92, and 0.92 for [2-15N]-, [U-14C]-, and
      [3,4-3H]glutamine, respectively). Volumes of distribution for each tracer (362 +/
      58, 433 +/- 51, and 446 +/- 63 ml/kg) and the transfer rate constants (0.0224 +/
      0.0020, 0.0222 +/- 0.0020, and 0.0240 +/- 0.0023 min(-1)) for [2-15N]-, [U-14C]
      , and [3,4-3H]glutamine, respectively, were not significantly different from one
      another. However, turnover of glutamine determined with [3,4-3H]glutamine (6.14
      +/- 0.54 micromol x kg(-1) x min(-1)) exceeded that determined with [U
      14C]glutamine (5.72 +/- 0.541 micromol x kg(-1) x min(-1); P < 0.03), which in
      turn exceeded that determined with [2-15N]glutamine (4.67 +/- 0.39 micromol x kg(
      1) x min(-1), P < 0.01). The monocompartmental non-steady-state equations of both
      DeBodo et al. (DeBodo, R., R. Steele, A. Dunn, and J. Bishop. Rec. Prog. Horm.
      Res. 19: 445-448, 1963) and Finegood et al. (Finegood, D., R. Bergman, and M.
      Vranic. Diabetes 36: 914-924, 1987) yielded acceptable approximations of
      predicted rates of glutamine plasma appearance with deviations from predicted
      rates from 0.2 to 1.6% (Finegood et al.) and from 0.1 to 8.2% (DeBodo et al.).
      Use of a 0.75 pool fraction most closely approximated predicted rates.

PMID- 9142884
TI  - rhIGF-I administration in humans: differential metabolic effects of bolus vs.
      continuous subcutaneous delivery.
AB  - The metabolic effects of recombinant human insulin-like growth factor I (rhIGF-I)
      were compared using bolus vs. continuous subcutaneous infusions. Subjects (n = 5,
      29 +/- 3 yr) received rhIGF-I as subcutaneous infusions by a Minimed pump (200
      microg x kg(-1) x day(-1) over 16 h/day), and their data were compared with those
      of subjects (n = 6, 24 +/- 2 yr) who received subcutaneous 200 microg x kg(-1) x
      day(-1) injections twice a day. L-[1-14C]leucine and [6,6-2H2]glucose infusion
      studies and indirect calorimetry were performed, and total and free IGF-I,
      insulin, and glucose concentrations were measured before and after 5-7 days of
      rhIGF-I. Estimates of protein breakdown, oxidation, and synthesis did not change
      after pump therapy; in contrast, after bolus doses, protein oxidation decreased
      (P = 0.001) and whole body protein synthesis increased (P = 0.04). There was no
      change in lipid oxidation after pump treatment, whereas the bolus group had lower
      lipid oxidation (P = 0.035). Both treatment modalities increased glucose
      oxidation (P < 0.02) and glucose production rates (P < 0.03). Overnight fasting
      insulin concentrations decreased in both groups, whereas plasma glucose remained
      invariant in the bolus group and decreased modestly in the pump group. Total IGF
      I concentrations increased comparably in both groups, but the increase in free
      IGF-I was greater in the bolus-treated group (P = 0.001). We conclude that, in GH
      sufficient postabsorptive individuals, the metabolic effects of rhIGF-I are in
      part dependent on the mode of administration, with a robust protein-anabolic
      effect when rhIGF-I is given as twice daily bolus injections but no detectable
      effect on protein turnover after a continuous mode of delivery. There were higher
      free IGF-I levels in the bolus-treated subjects, suggesting that this form of the
      molecule may be important for mediating IGF-I's protein-anabolic effects at the
      tissue level. The data also suggest that carbohydrate metabolism is more
      responsive than protein metabolism to the continuous subcutaneous modality of
      rhIGF-I administration. Even though the mechanism of these differences in
      metabolic effects is not entirely clear, it should be taken into account when
      patients are given rhIGF-I as prolonged treatment.

PMID- 9142885
TI  - Insulin secretion in adult rats that had experienced different underfeeding
      patterns during their development.
AB  - Four populations of 70-day-old undernourished rats were studied. All rats were
      submitted to a 65% restriction of food intake as follows: 1) undernutrition of
      the mother from day 14 of gestation until birth only (fetal period, group F), 2)
      undernourished during fetal and suckling periods only (group FS), 3)
      undernourished from day 14 of gestation until day 70 of life (group FSA), and 4)
      undernourished from day 28 of life until day 70 (group A). Body weight, plasma
      glucose, glucose tolerance, basal plasma insulin, in vivo glucose-induced insulin
      secretion, pancreatic insulin content, and in vitro response of isolated islets
      to glucose and amino acids were investigated. Islet insulin content decreased in
      all four groups studied, and islet mass was found reduced in group FSA. Glucose
      tolerance was decreased in group A, and in vitro response of islets decreased in
      both groups FSA and A. We conclude that two different adaptive processes should
      be considered: the possible long-term consequences of impaired pancreas
      development due to inadequate perinatal nutrition and the functional alteration
      of insulin secretion to undernutrition in adulthood.

PMID- 9142887
TI  - Role of glycogen concentration and epinephrine on glucose uptake in rat
      epitrochlearis muscle.
AB  - The effects of diet-manipulated variations in muscle glycogen concentration and
      epinephrine on glucose uptake were studied in epitrochlearis muscles from Wistar
      rats. Both basal and insulin-stimulated glucose uptake [measured with a tracer
      amount of 2-[1,2-3H(N)]deoxy-D-glucose] inversely correlated with initial
      glycogen concentration (glycogen concentration vs. basal glucose uptake:
      Spearman's rho = -0.76, n = 84, P < 0.000001; glycogen concentration vs. insulin
      stimulated glucose uptake: Spearman's rho = -0.67, n = 44, P < 0.00001). Two
      fasting-refeeding procedures were used that resulted in differences in muscle
      glycogen concentrations, although with similar treatment for the last 48 h before
      the experiment. In the rats with the lower glycogen concentration, basal as well
      as insulin-stimulated glucose uptake was elevated. The muscle glycogen
      concentration had no effect on epinephrine-stimulated glycogenolysis.
      Epinephrine, however, was found to reduce basal glucose uptake in all groups.
      These results suggest that 1) the glycogen concentration participates in the
      regulation of both basal and insulin-stimulated glucose uptake in skeletal
      muscle, 2) the magnitude of epinephrine-stimulated glycogen breakdown is
      independent of the glycogen concentration, and 3) epinephrine inhibits basal
      glucose uptake at all glycogen concentrations.

PMID- 9142886
TI  - Malonyl-CoA regulation in skeletal muscle: its link to cell citrate and the
      glucose-fatty acid cycle.
AB  - Malonyl-CoA is an inhibitor of carnitine palmitoyltransferase I, the enzyme that
      controls the oxidation of fatty acids by regulating their transfer into the
      mitochondria. Despite this, knowledge of how malonyl-CoA levels are regulated in
      skeletal muscle, the major site of fatty acid oxidation, is limited. Two- to
      fivefold increases in malonyl-CoA occur in rat soleus muscles incubated with
      glucose or glucose plus insulin for 20 min [Saha, A. K., T. G. Kurowski, and N.
      B. Ruderman. Am. J. Physiol. 269 (Endocrinol. Metab. 32): E283-E289, 1995]. In
      addition, as reported here, acetoacetate in the presence of glucose increases
      malonyl-CoA levels in the incubated soleus. The increases in malonyl-CoA in all
      of these situations correlated closely with increases in the concentration of
      citrate (r2 = 0.64) and to an even greater extent the sum of citrate plus malate
      (r2 = 0.90), an antiporter for citrate efflux from the mitochondria. Where
      measured, no increase in the activity of acetyl-CoA carboxylase (ACC) was found.
      Inhibition of ATP citrate lyase with hydroxycitrate markedly diminished the
      increases in malonyl-CoA in these muscles, indicating that citrate was the major
      substrate for the malonyl-CoA precursor, cytosolic acetyl-CoA. Studies with
      enzyme purified by immunoprecipitation indicated that the observed increases in
      citrate could have also allosterically activated ACC. The results suggest that in
      the presence of glucose, insulin and acetoacetate acutely increase malonyl-CoA
      levels in the incubated soleus by increasing the cytosolic concentration of
      citrate. This novel mechanism could complement the glucose-fatty acid cycle in
      determining how muscle chooses its fuels. It could also provide a means by which
      glucose acutely modulates signal transduction in muscle and other cells (e.g.,
      the pancreatic beta-cell) in which its metabolism is determined by substrate
      availability.

PMID- 9142888
TI  - Anti-TNF treatment does not reverse the abnormalities in lipid metabolism of the
      obese Zucker rat.
AB  - Because obesity, insulin resistance, and hyperlipidemia are often associated, and
      recent evidence suggests that the cytokine tumor necrosis factor-alpha (TNF) may
      influence the activity of insulin in various target tissues, the present study
      was designed to see whether TNF was also associated with the changes in lipid
      metabolism that lead to hyperlipidemia in the obese model of the Zucker rat. A
      polyclonal goat anti-rat TNF antibody was subcutaneously administered to Zucker
      rats for 4 days to block TNF actions. The results indicate that none of the
      alterations in lipid metabolism seen in the obese animals were reversed by the
      anti-TNF treatment. This was the case for the lipogenic rate in liver and adipose
      tissue, the disposal of an exogenous [14C]triolein load, adipose tissue
      lipoprotein lipase activity, and the hypertriglyceridemia. Measurements of
      lipolysis in adipose tissue slices from the anti-TNF-treated animals also did not
      show any significant effect of the treatment. In conclusion, TNF does not seem to
      be involved in the abnormalities of lipid metabolism observed in the obese Zucker
      rat.

PMID- 9142889
TI  - Phosphatidylinositol 3-kinase and dynamics of insulin resistance in denervated
      slow and fast muscles in vivo.
AB  - Regulation of glucose uptake by 1- and 3-day denervated soleus (slow-twitch) and
      plantaris (fast-twitch) muscles in vivo was investigated. One day after
      denervation, soleus and plantaris muscles exhibited 62 and 65% decreases in
      insulin-stimulated 2-deoxyglucose uptake, respectively, compared with
      corresponding control muscles. At this interval, denervated muscles showed no
      alterations in insulin receptor binding and activity, amount and activity of
      phosphatidylinositol 3-kinase, and amounts of GLUT-1 and GLUT-4. Three days after
      denervation, there was no increase in 2-deoxyglucose uptake in response to
      insulin in soleus muscle, whereas plantaris muscle exhibited a 158% increase in
      basal and an almost normal absolute increment in insulin-stimulated uptake.
      Despite these differences, denervated soleus and plantaris muscles exhibited
      comparable decreases in insulin-stimulated activities of the insulin receptor
      (approximately 40%) and phosphatidylinositol 3-kinase (approximately 50%) and a
      pronounced decrease in GLUT-4. An increase in GLUT-1 in plantaris, but not
      soleus, muscle 3 days after denervation is consistent with augmented basal 2
      deoxyglucose uptake in plantaris muscle at this interval. These results
      demonstrate that, in denervated muscles, there is a clear dissociation between
      insulin-stimulated 2-deoxyglucose uptake and upstream events involved in insulin
      stimulated glucose uptake.

PMID- 9142891
TI  - Whole body and splanchnic metabolic and circulatory effects of glucose during
      beta-adrenergic receptor inhibition.
AB  - The aim of the study was to assess the possible contribution of adrenergic
      mechanisms to the thermogenic and circulatory effects of glucose ingestion. With
      the use of indirect calorimetry and arterial, pulmonary arterial, and hepatic
      venous catheterization, whole body and splanchnic oxygen uptake and blood flow
      were examined in nine propranolol-treated healthy male volunteers before and
      during 2 h after oral ingestion of 75 g of glucose. The glucose effects were
      compared with those in nine untreated controls. After propranolol, the glucose
      induced rise in splanchnic blood flow was reduced by approximately 60%, and the
      hepatic venous glucose release to the systemic circulation was significantly
      delayed. Glucose-induced increments in pulmonary and splanchnic oxygen uptake and
      cardiac output were similar in the two groups. It is concluded that adrenergic
      mechanisms contribute to the glucose-induced rise in splanchnic blood flow and
      thereby probably to the time course for intestinal absorption of nutrients. It is
      suggested that the magnitude of glucose-induced thermogenesis is independent of
      adrenergic stimulation.

PMID- 9142890
TI  - Regulation of insulin secretion via ATP-sensitive K+ channel independent
      mechanisms: role of phospholipase C.
AB  - Groups of rat or mouse islets were isolated and perifused with 20 mM glucose plus
      200 microM diazoxide. The further addition of 30 mM K+ resulted in a rapid and
      sustained biphasic insulin secretory response. The onset of secretion in response
      to the addition of K+ was comparable in both species, but the magnitude of the
      response was significantly greater from rat islets. After the labeling of islet
      phosphoinositide pools with 2-[3H]inositol, the accumulation of labeled inositol
      phosphates (IP) in response to 30 mM K+ addition in the simultaneous presence of
      20 mM glucose plus diazoxide was assessed. The addition of 30 mM K+ significantly
      increased IP accumulation approximately 300% in rat islets, whereas only an
      insignificant 25-30% increase was observed in mouse islets. The protein kinase C
      inhibitor staurosporine (50 nM) dramatically reduced the sustained secretory
      response from rat islets in the presence of 30 mM K+, 20 mM glucose, and
      diazoxide. Its effect was minimal on mouse islets and a significant inhibitory
      effect on insulin secretion was observed only during the final 5 min of the
      perifusion. The further addition of carbachol, an agonist that activates an
      isozyme of phospholipase C distinct from that activated by glucose, together with
      K+, 20 mM glucose, plus diazoxide resulted in a sustained amplification of
      insulin secretion from mouse but not rat islets. K+ (30 mM)-induced insulin
      secretion in the presence of 3 mM glucose was similar from perifused rat or mouse
      islets, a finding that would seem to preclude the activation of voltage-regulated
      Ca2+ channels as the pertinent difference. These results confirm previous
      observations with these species and document another anomaly that exists between
      the responses of rat islets compared with mouse islets. The inability to activate
      a nutrient- and calcium-regulated phospholipase C isozyme in mouse islets to the
      same extent as in rat islets appears to account, at least in part, for these
      different insulin secretory responses under these unique conditions.

PMID- 9142892
TI  - Human skeletal muscle protein breakdown during spaceflight.
AB  - Human spaceflight is associated with a loss of body protein. Excretion of 3
      methylhistidine (3-MH) in the urine is a useful measurement of myofibrillar
      protein breakdown. Bed rest, particularly with 6 degrees head-down tilt, is an
      accepted ground-based model for human spaceflight. The objectives of this report
      were to compare 3-MH excretion from two Life Sciences shuttle missions (duration
      9.5 and 15 days, n = 9) and from 17 days of bed rest (n = 7) with 6 degrees head
      down tilt. The bed rest study was designed to mimic an actual Life Sciences
      spaceflight and so incorporated an extensive battery of physiological tests
      focused on the musculoskeletal system. Results showed that nitrogen retention,
      based on excretion of nitrogen in the urine, was reduced during both bed rest
      [from 22 +/- 1 to 1 +/- 5 mg N x kg(-1) x day(-1) (n = 7; P < 0.05)] and
      spaceflight [from 57 +/- 9 to 19 +/- 3 mg N x kg(-1) x day(-1) (n = 9; P <
      0.05)]. 3-MH excretion was unchanged with either bed rest [pre-bed rest 5.30 +/-
      0.29 vs. bed rest 5.71 +/- 0.30 micromol 3-MH x kg(-1) x day(-1), n = 7; P = not
      significant (NS)] or spaceflight [preflight 4.98 +/- 0.37 vs. 4.59 +/- 0.39
      micromol 3-MH x kg(-1) x day(-1) in-flight, n = 9; P = NS]. We conclude that 1) 3
      MH excretion was unaffected by spaceflight on the shuttle or with bed rest plus
      exercise, and 2) because protein breakdown (elevated 3-MH) was increased on
      Skylab but not on the shuttle, it follows that muscle protein breakdown is not an
      inevitable consequence of spaceflight.

PMID- 9142893
TI  - Measurement and modeling of glucose-6-phosphatase in pancreatic islets.
AB  - In the beta-cells of the pancreas, glucose phosphorylation carried out by
      glucokinase is the rate-controlling step in glycolysis, and the kinetic
      characteristics of glucokinase govern to a high degree the dose-response
      relationship between glucose and insulin release. Because glucose-6-phosphatase
      (G-6-Pase) opposes the action of glucokinase, it may have a regulatory role in
      the release of insulin in response to glucose if the enzyme is present in the
      beta-cells. A number of researchers have reported finding high levels of G-6-Pase
      in islets, but quantitation of its activity remains controversial, mainly because
      of difficulties in solubilizing a particulate enzyme. Therefore a method
      developed to measure functional glucose phosphorylation activity in intact brain
      was applied (Chi, M. M.-Y., M. E. Pusateri, J. G. Carter, B. J. Norris, D. B.
      McDougal, Jr., and O. H. Lowry. Anal. Biochem. 161: 508-513, 1987), and the rates
      of accumulation and disappearance of 2-deoxyglucose 6-phosphate (DG-6-P) in
      freshly harvested islets were determined as a measure of glucose cycling. Islets
      were incubated in the presence of 30 mM 2-deoxyglucose (DG) for 60 min, and
      subsequently the incubation medium was replaced with medium containing no DG, but
      instead high levels of mannoheptulose as a blocker of phosphorylation. The
      content of DG-6-P in the islets was measured at strategic times during the
      protocol. As predicted by a mathematical model, DG-6-P accumulated in the
      presence of DG and decayed after its washout. Both of these results are
      consistent with islets containing dephosphorylation activity for this substrate.
      The kinetic curves were fit using a mathematical model, and the maximal G-6-Pase
      activity was estimated to be 0.13 +/- 0.005 micromol x g(-1) x min(-1). However,
      when the physiological effect of this amount of G-6-Pase activity was assessed by
      use of a model of glycolysis, it was found that the impact on glucose cycling and
      usage was insignificant. It was concluded that normal islets do contain
      measurable activity for dephosphorylating glucose 6-phosphate but that this
      enzymatic reaction does not play a role in glucose metabolism and sensing by the
      normal beta-cell.

PMID- 9142894
TI  - Clenbuterol, a beta2-adrenoceptor agonist, reduces scoliosis due to partial
      transection of rat spinal cord.
AB  - Injury to the spinal cord often results in abnormal lateral curvature of the
      spine, or scoliosis, that is associated with neuromuscular weakness. The lateral
      curvature of the spine is thought to be a consequence of insufficient or
      asymmetrical loading of the vertebrae. To study neuromuscular scoliosis, an
      animal model of spinal cord injury was used in which the spinal cord was
      partially (3/4) transected, with the left lateral columns left intact. Partial
      transection of the spinal cord in the rat caused scoliosis that was maximal four
      to five vertebrae distal to the lesion site. As in previous experiments involving
      unilateral spinal cord lesions, the scoliotic curves were convex on the weakened
      side. Subtotal transection at T5 or T11 resulted in lateral displacement of
      vertebrae T9-T12 or L2-L5, respectively, of up to 11 mm. Interestingly, this
      vertebral displacement is greatly reduced by clenbuterol, a beta2-adrenoceptor
      agonist that has been found to retard loss of muscle contractility and bone
      mineralization due to denervation. Together these results suggest that
      stimulation of beta2-receptors opposes vertebral unloading due to neuromuscular
      weakness and thereby acts as a countermeasure to scoliosis.

PMID- 9142895
TI  - Chronic insulin hypoglycemia induces GLUT-3 protein in rat brain neurons.
AB  - Near-normalization of glycemia reduces the risks of chronic diabetic
      complications but increases the risk of serious hypoglycemia. Hypoglycemia can
      impair neuronal function in the brain and diminish awareness of subsequent
      hypoglycemic episodes, yet little is known about how neurons adapt to
      hypoglycemia. This study tests the hypothesis that isoform-specific alterations
      in brain glucose transport proteins occur in response to chronic hypoglycemia. To
      study this, groups of rats were injected with approximately 25 U/kg ultralente
      insulin daily at 1700 for 8 days to maintain hypoglycemia. Vascular-free and
      microvessel membrane fractions from brain were prepared for immunoblot analysis
      of GLUT-1 and GLUT-3 by use of isoform-specific antisera. Insulin treatment
      reduced blood glucose levels from 4.0 +/- 0.1 (vehicle-injected controls) to 1.7
      +/- 0.1 mmol/l on day 8 (P < 0.001) and increased GLUT-3 protein expression
      (175.6% of control; P < 0.05). Microvascular GLUT-1 (55 kDa) tended to increase
      (195.6% of controls; P = 0.08) variably, whereas nonvascular GLUT-1 (45 kDa) was
      unchanged. We conclude that neuronal glucose transport protein (GLUT-3)
      expression adapts to chronic hypoglycemia. This adaptation may spare neuronal
      energy metabolism but could dampen neuronal signaling of glucose deprivation.

PMID- 9142896
TI  - Speed of glucagon's glycogenolytic effect.

PMID- 9142897
TI  - Colonic smooth muscle cells possess a different subtype of somatostatin receptor
      from gastric smooth muscle cells.
AB  - Somatostatin (SS) alters colonic motility. To investigate whether SS has a direct
      effect on colonic smooth muscle cells, we prepared isolated muscle cells from the
      descending guinea pig colon and compared the effects of SS with those on isolated
      gastric smooth muscle cells. In gastric cells, SS had no effect on carbachol
      induced contraction, whereas in colonic cells it caused inhibition. In colonic
      muscle cells, SS-28 caused >85% inhibition of contraction by cholecystokinin
      octapeptide (CCK-8), bombesin, 12-O-tetradecanoylphorbol-13-acetate, and
      ionomycin, whereas it had no effect on contraction by these agents in gastric
      cells. In gastric cells, SS inhibited relaxation. Three synthetic SS analogs had
      different relative affinities for causing effects in gastric and colonic cells.
      Pertussis toxin inhibited the action of SS-28 in each muscle cell type by 50-75%.
      SS-28 alone had a small contractile effect on cells from the circular layer of
      the colon. SS-28 inhibited carbachol-induced contraction in colonic cells from
      both the longitudinal and circular layers. These results demonstrate that the
      action of SS differs in colonic and gastric smooth muscle cells. SS inhibits
      contractants in colonic cells and relaxants in gastric cells. In colonic cells,
      SS has a weak contractile effect due to an effect on circular muscle cells and an
      inhibitory effect on cells from both longitudinal and circular layers. A
      different SS receptor subtype mediates the actions of SS in colonic and gastric
      muscle cells. In both cell types, the actions of SS are mediated by pertussis
      toxin-sensitive and -insensitive G proteins.

PMID- 9142898
TI  - A unique myosin isoform transition in cat striated external anal sphincter muscle
      induced by denervation.
AB  - Denervation of limb and trunk muscles leads to characteristic changes in their
      biochemical properties. However, the effects of denervation of the striated
      external anal sphincter (EAS) muscle have not been studied, even though
      denervation is a common etiology for fecal incontinence. The present study
      reports effects ofdenervation of the cat EAS and compares them with changes in a
      denervated limb muscle [cat extensor digitorum longus (EDL)]. Nerves supplying
      the EAS and the EDL were sectioned in anesthetized cats, which were allowed to
      recover and live for 10, 30, or 60 days. Their muscles were then excised, and
      myofibrillar proteins were isolated. Myosin heavy chain (MHC) isoform composition
      was measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The
      EDL and EAS showed progressive increases in MHC type IIA and progressive
      decreases in MHC type IIB at 10, 30, and 60 days. MHC type I progressively
      increased in the EDL but showed no change in the EAS. We hypothesize that this
      distinctive transition is related to the unique embryological origin and function
      of the EAS.

PMID- 9142899
TI  - Effect of short-chain fatty acids on paracellular permeability in Caco-2
      intestinal epithelium model.
AB  - Control of paracellular permeability in the colonic epithelium is fundamental to
      its functional competence. This study examines the relationship between
      physiologically relevant short-chain fatty acids (SCFAs) and paracellular
      permeability using the Caco-2 cell line model. Butyrate induced a concentration
      dependent, reversible increase in transepithelial resistance (TER) that was
      maximal after 72 h. Butyrate (2 mM) increased TER by 299 +/- 69% (mean +/- SE; n
      = 5; P < 0.05; t-test) and reduced mannitol flux to 52 +/- 11% (P < 0.05) of
      control. The effect of butyrate was dependent on protein synthesis and gene
      transcription but not dependent on its oxidation or activation of adenosine 3',5'
      cyclic monophosphate. The other SCFAs, propionate and acetate, also induced a
      concentration-dependent increase in TER. The effect of butyrate paralleled
      changes in cellular differentiation, because alkaline phosphatase activity,
      carcinoembryonic antigen expression, and dome formation were increased.
      Furthermore, other differentiating agents (dimethyl sulfoxide and retinoic acid)
      also increased TER. Thus SCFAs reduce paracellular permeability in the Caco-2
      cell line, possibly by promotion of a more differentiated phenotype. If such an
      effect occurs in vivo, it may have ramifications for the biology and pathobiology
      of colonic mucosa.

PMID- 9142900
TI  - Polyamines are necessary for normal expression of the transforming growth factor
      beta gene during cell migration.
AB  - The current study tests the hypothesis that intracellular polyamines are involved
      in the regulation of gene expression of transforming growth factor-beta (TGF
      beta) during epithelial cell migration after wounding. Administration of alpha
      difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase
      (the first rate-limiting enzyme for polyamine synthesis), depleted cellular
      polyamines putrescine, spermidine, and spermine in IEC-6 cells. DFMO also
      significantly reduced basal levels of TGF-beta mRNA in unwounded cells. Gene
      expression of TGF-beta was dramatically stimulated after wounding of a monolayer
      of cells not treated with DFMO. TGF-beta mRNA levels significantly increased from
      4 to 12 h after wounding, peaking at 6 h at a level eight times the prewounding
      control. Increased levels of TGF-beta mRNA in IEC-6 cells after wounding were
      paralleled by an increase in TGF-beta content. Depletion of intracellular
      polyamines in DFMO-treated cells significantly inhibited increased expression of
      the TGF-beta gene in response to wounding. Cell migration also significantly
      decreased in DFMO-treated cells. In the presence of DFMO, exogenous TGF-beta
      restored cell migration to normal. These results indicate that 1) polyamine
      depletion induced by DFMO is associated with decreases in the expression of the
      TGF-beta gene and cell migration in IEC-6 cells and 2) exogenous TGF-beta
      reverses the inhibitory effect of polyamine depletion on cell migration. These
      findings suggest that polyamines are required for epithelial cell migration in
      association with their ability to regulate TGF-beta gene expression.

PMID- 9142902
TI  - Interleukin-2-induced hepatic injury involves temporal patterns of cell adhesion
      in the microcirculation.
AB  - The treatment of metastatic cancer with interleukin-2 (IL-2) is limited by
      systemic toxicities, including hepatic dysfunction. The objective of this study
      was to determine the cellular mechanisms of IL-2-induced hepatic injury.
      Intravital microscopy was used for the direct observation of the murine hepatic
      microcirculation after 2 h, 2 days, and 4 days of IL-2 treatment. At each
      interval, leukocyte- and platelet-endothelial adherence were observed and
      quantitated. Simultaneously, sinusoidal perfusion, serum levels of glutamate
      pyruvate transaminase, and edema were measured as indexes of hepatic toxicity. IL
      2 increased neutrophil adhesion acutely in association with decreased sinusoidal
      perfusion. Leukocyte adhesion subsided at 2 days, but platelet-endothelial
      interactions were enhanced and 40% of mice receiving IL-2 had microvascular
      thrombi. These effects occurred in conjunction with decreased sinusoidal
      perfusion and the development of hepatic edema. After 4 days of IL-2, maximal
      hepatic edema, hypoperfusion, and increased serum levels of glutamate pyruvate
      transaminase were associated with increased lymphocyte adhesion and microvascular
      thrombosis. These data suggest coordinated, temporal roles of leukocytes and
      platelets in the generation of IL-2-induced hepatic injury.

PMID- 9142903
TI  - Effect of chronic inflammation on electrolyte transport in rabbit ileal villus
      and crypt cells.
AB  - The effect of chronic inflammation on electrolyte transport in rabbit ileal
      villus and crypt cells was determined with the use of a rabbit model of chronic
      ileitis. In both cells, Na+/H+ exchange was monitored by following recovery from
      an acid load, and Cl-/HCO3- exchange was monitored by following recovery from an
      alkaline load. In villus cells, recovery from an acid load was not affected;
      however, recovery from an alkaline load was slowed. These data suggest that
      chronic inflammation inhibits Cl-/HCO3- exchange in villus cells. In contrast, in
      crypt cells, recovery from an alkaline load was unaffected, whereas recovery from
      an acid load was accelerated. These data suggest that chronic inflammation
      stimulates Na+/H+ exchange in crypt cells. Inhibition of Cl-/HCO3- exchange in
      villus cells would be expected to inhibit coupled NaCl absorption, which occurs
      by the coupling of brush-border membrane (BBM) Na+/H+ and Cl-/HCO3- exchange.
      Stimulation of Na+/H+ exchange in crypt cells, known to be present only on the
      basolateral membrane, alkalinizes the cell. This alkalinization may stimulate BBM
      Cl-/HCO3- exchange, resulting in HCO3- secretion. Thus these unique alterations
      in transporter activity suggest that different endogenous immune-inflammatory
      mediators may have differing effects on specific transporters in villus and crypt
      cells in the chronically inflamed ileum.

PMID- 9142901
TI  - Molecular mechanisms for somatostatin inhibition of c-fos gene expression.
AB  - We reported previously that somatostatin inhibits the expression of the immediate
      early gene c-fos. Accordingly, we characterized the molecular mechanisms by which
      somatostatin inhibits c-fos gene expression. Because growth factors activate c
      fos through a region of its promoter known as the serum response element [SRE;
      base pairs (bp) -357 to -276] we transfected rat pituitary adenoma cells (GH3)
      with plasmids containing the SRE or the SRE core fragment (bp -320 to -298)
      upstream of the luciferase reporter gene. Epidermal growth factor (EGF)
      stimulated SRE-luciferase activity, and this effect was inhibited by somatostatin
      and by the analog MK-678. Identical results were obtained with the SRE core
      plasmid, demonstrating that the sequence between bp -320 and -298 of the c-fos
      promoter is a somatostatin response element. Because the extracellular signal
      regulated protein kinases (ERKs) induce the SRE via phosphorylation of
      transcription factors such as Elk-1, we examined the effect of somatostatin on
      ERK phosphorylation and activation. EGF stimulated tyrosine phosphorylation of
      ERK2, and MK-678 attenuated this effect. In experiments using in-gel kinase
      assays, MK-678 also inhibited EGF-stimulated ERK activity via a pertussis toxin
      sensitive pathway, and this effect resulted in inhibition of Elk-1
      transcriptional activity. Our data suggest that one mechanism of somatostatin
      action involves inhibition of ERK activity, Elk-1 phosphorylation and
      transcriptional activation, and ultimately c-fos gene transcription.

PMID- 9142904
TI  - Electrophysiological characterization of cultured hepatic stellate cells in rats.
AB  - This study aimed to examine electrophysiological properties of cultured rat
      hepatic stellate cells (HSCs) using the whole cell configuration of patch-clamp
      technique. At least three different current components were identified. First,
      when the membrane was depolarized to voltages more positive than -40 mV, a
      transient outward K+ current was evoked. Second, membrane hyperpolarization below
      -60 mV evoked a sustained and inward-rectifying K+ current. The third component
      was a current flowing outward, which was activated when the cell was depolarized
      more positively than 0 mV. The channel for this current allowed Na+, K+, and Cl-
      to pass nonspecifically, suggesting the presence of hemi gap-junctional channel.
      Furthermore, a laser photobleaching technique revealed the presence of gap
      junctions between adjacent HSCs. A voltage-gated Ca2+ current, which is known to
      occur in smooth muscle cells, was searched for but was not detectable. These
      results suggest that membrane potential of HSCs is determined specifically by the
      two distinct K+ channels and by an intercellular mechanism involving gap
      junctional communication.

PMID- 9142905
TI  - Immunohistochemical localization of cysteine-rich intestinal protein in rat small
      intestine.
AB  - Cysteine-rich intestinal protein (CRIP) is a LIM (cysteine-rich motif of leu-11,
      isl-1, and mec-3 genes) domain protein with a double zinc finger motif. The
      protein is abundantly expressed in the intestine, peritoneal macrophages, and
      peripheral blood mononuclear cells. The function of CRIP is not known. The
      purpose of this study was to determine the cellular distribution of CRIP in rat
      intestine, as an initial step toward eventual determination of a function.
      Immunohistochemical and immunogold labeling electron microscopy using a purified
      polyclonal rabbit antibody to a synthetic peptide representing a zinc finger
      domain of rat CRIP were carried out on sections of rat duodenum. Western blotting
      was used to detect signal specificity of the antibodies. These
      immunohistochemical and electron microscopy studies showed particularly high
      abundance of CRIP in the cytoplasmic granules of Paneth cells of the intestine.
      Some evidence of CRIP expression was also found in cells of the villus tip, but
      abundance was less than that found in the Paneth cells. The localization of CRIP
      in Paneth cells and its presence in mononuclear cells suggests that CRIP may be
      involved in host defense mechanisms and/or tissue differentiation/remodeling
      processes common to these cell types.

PMID- 9142906
TI  - Role of nitric oxide in hypoxia-induced colonic dysfunction in the neonatal rat.
AB  - In addition to being an important mediator in the regulation of intestinal
      integrity, nitric oxide (NO), when produced in large quantities by the inducible
      isoform of NO synthase, can also be cytotoxic. The aim of this study was to
      examine the role of NO in hypoxia-induced colonic injury in neonatal rats. Rats
      (10-12 days old) were exposed to a hypoxic environment of 14% O2-86% N2 for 30
      min. NO synthase activity in colonic tissue was measured via the conversion of L
      [14C]arginine to L-[14C]citrulline. Epithelial permeability was assessed by
      measuring the plasma-to-lumen flux of [3H]mannitol or the luminal protein content
      of colonic lavage. The role of neutrophils was assessed by pretreatment with
      antineutrophil serum (200 microl/kg ip) and measurement of tissue myeloperoxidase
      activity. Hypoxia resulted in an elevation in the activity of the inducible Ca2+
      independent isoform of NO synthase in colonic tissue, which was maximal between 4
      and 6 h posthypoxia and was associated with an increase in myeloperoxidase
      activity, [3H]mannitol flux, luminal protein content, and histological damage.
      These effects were attenuated by pretreatment with dexamethasone or the NO
      synthase inhibitors aminoguanidine and N(G)-nitro-L-arginine methyl ester,
      whereas the inactive stereoisomer N(G)-nitro-D-arginine methyl ester was without
      effect. Pretreatment with antineutrophil serum significantly reduced circulating
      neutrophils, myeloperoxidase activity, and Ca2+-independent NO synthase activity.
      These findings demonstrate that hypoxia-induced colonic injury in neonatal rats
      is associated with elevated NO synthase activity, which is related to an increase
      in neutrophil infiltration.

PMID- 9142907
TI  - Nitric oxide and gallbladder motility in prairie dogs.
AB  - In this study we evaluated the role of nitric oxide (NO) on gallbladder motility
      in the normal prairie dog by 1) immunohistochemistry, 2) an enzymatic assay for
      NO synthase (NOS), and 3) an in vivo model to measure whole gallbladder tone and
      contractility. NOS was localized to gallbladder mucosal cells by NADPH-diaphorase
      and polyclonal antibodies to a constitutive brain NOS. Gallbladder mucosal
      homogenates demonstrated total NOS activity in the range of 578 +/- 115 pmol x mg
      protein(-1) x 30 min(-1). Blockade of NOS activity in vivo using N(omega)-nitro-L
      arginine methyl ester resulted in an up to 80% increase in gallbladder tone from
      basal. A 40% increase in tone was seen with methylene blue, suggesting that tone
      was maintained by both NO activation of guanylate cyclase and possibly direct
      effects on Ca2+ channels. An exogenous nitrosothiol, S-nitroso-N-acetyl-cysteine,
      abolished cholecystokinin (CCK) octapeptide and bethanechol-stimulated
      gallbladder contraction. We conclude that the prairie dog gallbladder contains
      constitutive NOS and synthesizes NO, which is important for the maintenance of
      basal gallbladder tone and is an inhibitor of the contractile response of the
      gallbladder to agonists such as CCK and bethanechol.

PMID- 9142908
TI  - Common bile duct ligation in the rat: a model of intrapulmonary vasodilatation
      and hepatopulmonary syndrome.
AB  - Hepatopulmonary syndrome (HPS) causes impaired oxygenation due to intrapulmonary
      vasodilatation in patients with cirrhosis. Chronic common bile duct ligation
      (CBDL) in the rat results in gas-exchange abnormalities similar to HPS, but
      intrapulmonary vasodilatation has not been evaluated. We assess intrapulmonary
      vasodilatation, measured in vivo, after CBDL. Sham, 2- and 5-wk CBDL, and 3-wk
      partial portal vein ligated (PVL) rats had hepatic and lung injury, portal
      pressure, and arterial blood gases assessed. The pulmonary microcirculation was
      evaluated by injecting microspheres (size range 5.5-10 microm) intravenously and
      measuring the size and number of microspheres bypassing the lungs in arterial
      blood. CBDL animals developed progressive hepatic injury and portal hypertension
      accompanied by gas-exchange abnormalities and intrapulmonary vasodilatation. PVL
      animals, with a similar degree of portal hypertension, did not develop
      intrapulmonary vasodilatation or abnormal gas exchange. No lung injury was
      observed. CBDL, but not PVL, causes progressive intrapulmonary vasodilatation,
      which accompanies worsening arterial gas exchange. These findings validate CBDL
      as a model to study HPS.

PMID- 9142909
TI  - Substance P and bradykinin stimulate plasma extravasation in the mouse
      gastrointestinal tract and pancreas.
AB  - Neurogenic inflammation is mediated by release of tachykinins from sensory
      nerves, which stimulate plasma extravasation from postcapillary venules. Because
      there are conflicting results regarding the importance of neurogenic inflammation
      in the gastrointestinal tract, we quantified plasma extravasation using Evans
      blue and identified sites of the leak using Monastral blue in the mouse.
      Substance P and bradykinin stimulated extravasation from postcapillary venules in
      the stomach, small and large intestine, pancreas, urinary bladder, trachea, and
      skin by two- to sevenfold by interacting with NK1 and B2 receptors, respectively.
      Stimulation of sensory nerves with capsaicin also induced extravasation.
      Capsaicin- and bradykinin-stimulated extravasation was attenuated by an NK1
      receptor antagonist and is thus mediated by release of tachykinins and activation
      of the NK1 receptor. We conclude that 1) substance P stimulates extravasation in
      the gastrointestinal tract and pancreas of mice by interacting with the NK1
      receptors, and 2) capsaicin and bradykinin induce plasma extravasation by
      stimulating tachykinin release from sensory nerves. Thus neurogenic mechanisms
      mediate inflammation in the gastrointestinal tract and pancreas of the mouse.

PMID- 9142910
TI  - Mechanisms of CCK regulation of monitor peptide mRNA expression in pancreatic
      acinar AR42J cells.
AB  - We explored the mechanism(s) by which cholecystokinin (CCK) stimulation of AR42J
      rat pancreatoma cells results in increased mRNA expression of a CCK-releasing
      peptide [monitor peptide (MP)]. With the use of a newly established reverse
      transcription-polymerase chain reaction assay system, CCK was shown to increase
      the level of MP mRNA by about ninefold. When protein synthesis was blocked by
      addition of cycloheximide, the MP mRNA level remained unchanged in the presence
      of CCK. Inhibition of transcription with actinomycin D resulted in a half-life
      for MP mRNA of approximately 17 h, and this rate remained unchanged after CCK
      treatment, suggesting that CCK may regulate the MP mRNA level by influencing gene
      transcription. A-23187, bombesin, substance P, and carbachol increased the MP
      mRNA level. CoCl(2) abolished actions of both CCK and A-23187 on MP mRNA
      expression. Dibutyryl-adenosine 3',5'-cyclic monophosphate, forskolin, secretin,
      and vasoactive intestinal polypeptide had no effect on MP mRNA expression. 12-O
      tetradecanoylphorbol-13-acetate and phorbol 12,13-dibutyrate also failed to
      increase MP mRNA. It was therefore proposed that CCK stimulates MP mRNA
      expression of AR42J cells in a Ca2+-dependent and protein kinase C-independent
      manner.

PMID- 9142911
TI  - Cranial nerve modulation of human cortical swallowing motor pathways.
AB  - Animal data indicate that cortical swallowing pathways can be modulated by
      cranial nerve afferent stimulation. We therefore studied the effects of human
      trigeminal and vagal nerve excitation on the corticofugal pathways to the
      oropharynx and esophagus, using electromagnetic stimulation. Unilateral
      stimulation of either the trigeminal or vagus nerve evoked two distinct reflex
      electromyographic responses in the pharynx and esophagus, an early response
      (latency range 19-30 ms) and a late response (latency range 42-72 ms). In the
      mylohyoid muscles, however, only a single response was seen (latency range 36-64
      ms). Cortical stimulation also evoked electromyographic responses in the
      mylohyoid muscles, pharynx, and esophagus, with latencies of 8.5 +/- 0.3, 9.3 +/-
      0.3, and 10.1 +/- 0.4 ms, respectively. When either trigeminal or vagus nerve
      stimulation preceded cortical stimulation, the cortically evoked responses were
      facilitated, with maximal effects at interstimulation intervals of 30-200 ms for
      pharynx and esophagus (P < 0.02) and at interstimulation intervals of 50-100 ms
      for mylohyoid muscles (P < 0.05). Our results demonstrate that stimulation of
      human cranial nerve afferent fibers facilitates cortical swallowing motor
      pathways.

PMID- 9142912
TI  - TNF-alpha contributes to the pathogenesis of ethanol-induced gastric damage in
      cirrhotic rats.
AB  - Cirrhotic rats exhibit increased susceptibility to ethanol-induced gastric
      damage, but the underlying mechanism for this phenomenon remains unclear.
      Abnormalities of the gastric microcirculation have been reported that may
      contribute to the increased susceptibility to damage. Decreased gastric synthesis
      of prostaglandins also likely contributes to impaired mucosal defense in
      cirrhotic rats. Tumor necrosis factor-alpha (TNF-alpha) has been implicated in
      mucosal injury, and its synthesis can be inhibited by prostaglandins. Therefore,
      we hypothesized that TNF-alpha synthesis/ release is altered in cirrhotic rats
      and plays a role in the pathogenesis of ethanol-induced gastric damage. Cirrhosis
      was induced by bile duct ligation, whereas controls had sham operations. Topical
      application of 40% ethanol caused four times as much damage in cirrhotic rats
      than in controls. Basal plasma TNF-alpha levels did not differ between control
      and cirrhotic rats, although cirrhotic rats exhibited significantly higher levels
      of gastric TNF-alpha mRNA. Plasma TNF-alpha increased significantly in control
      and cirrhotic rats after ethanol administration. Inhibition of TNF-alpha
      synthesis/release with pentoxifylline, thalidomide, dexamethasone, or
      immunoneutralization of TNF-alpha (with anti-TNF-alpha) was found to
      significantly reduce the severity of ethanol-induced gastric mucosal damage in
      cirrhotic rats. We conclude that TNF-alpha contributes to the pathogenesis of
      ethanol-induced gastric damage in cirrhotic rats.

PMID- 9142913
TI  - Acute and neonatal capsaicin treatment inhibit jejunal amino acid absorption
      through a Na+-dependent mechanism.
AB  - It has recently been shown that capsaicin inhibits alanine absorption in rat
      jejunum via mechanisms that involve intestinal capsaicin-sensitive primary
      afferent (CSPA) fibers. This study provides further evidence that the effect of
      capsaicin is neurally mediated and demonstrates that CSPA fibers regulate Na+
      dependent amino acid absorption. In vivo, basal alanine absorption in rats
      neonatally treated with capsaicin was reduced by 35% below control. Furthermore,
      intraluminal perfusion of 400 microM capsaicin reduced jejunal alanine absorption
      by 31% in sham rats but had no significant effect in rats neonatally treated with
      capsaicin. In vitro, capsaicin significantly reduced uptake of alanine and
      proline by jejunal strips but had no effect on uptake of lysine. Tetrodotoxin
      (0.2 microM) partially blocked the effects of capsaicin but did not itself affect
      alanine absorption. Capsaicin reduced unidirectional mucosal-to-serosal alanine
      (1 mM) influx by 33%, an effect that becomes significant after 5 min of
      preincubation with capsaicin. Neonatal capsaicin treatment reduced basal alanine
      influx in jejunal strips by 37%; however, preincubation of these strips with
      capsaicin had no significant effect. Kinetic analysis of alanine steady-state
      uptake and influx by jejunal strips incubated with capsaicin revealed that
      capsaicin reduced the Na+-dependent component of alanine influx into intestinal
      epithelial cells. Long-term sensory denervation by capsaicin also decreased the
      Na+-dependent component of alanine absorption. These data suggest that intestinal
      capsaicin-sensitive primary afferent fibers regulate Na+-dependent amino acid
      absorption.

PMID- 9142914
TI  - Gastrin regulates the human histidine decarboxylase promoter through an AP-1
      dependent mechanism.
AB  - The histidine decarboxylase (HDC) gene is regulated transcriptionally by gastrin
      and phorbol 12-myristate 13-acetate (PMA) through a protein kinase C (PKC)
      related pathway. To determine the role of AP-1 (fos/jun) in the regulation of the
      HDC promoter, gastric cancer (AGS-B) cells stably expressing the cholecystokinin
      B/ gastrin receptor and the 1.8-kb human (h) HDC-luciferase (luc) construct were
      cotransfected with constructs expressing c-fos and c-jun. Overexpression of c-fos
      and c-jun activated the HDC promoter in a dose-dependent fashion in 1.8-kb hHDC
      luc/AGS-B cells as well as in transfected F9 embryonal carcinoma cells, which
      lack endogenous AP-1 activity. PMA was unable to activate the HDC promoter in F9
      cells, which were not transfected with c-fos and c-jun. Gastrin stimulation
      increased c-fos and c-jun mRNA abundance and AP-1-dependent transcriptional
      activity, as assessed by a reporter construct in which the CAT reporter gene is
      under the control of a 12-O-tetradecanoylphorbol-13-acetate response element
      multimer. Gastrin-stimulated HDC promoter activity was blocked by transfection of
      c-fos antisense and dominant negative c-jun expression constructs. Finally,
      overexpression of c-fos and c-jun activated the hHDC promoter through a
      downstream cis-acting element (gastrin response element), which does not bind AP
      1. In conclusion, activation of AP-1 is essential for gastrin-stimulated HDC
      transcription, but the mechanism appears to be indirect.

PMID- 9142915
TI  - Altered vascular norepinephrine responses in portal hypertensive intestine: role
      of PKA and guanylate cyclase.
AB  - The purpose of the present study was to determine whether selective blockade of
      adenosine 3',5'-cyclic monophosphate (cAMP)- or guanosine 3',5'-cyclic
      monophosphate (cGMP)-mediated events modulated norepinephrine responses in
      intestinal microvessels of normal and portal hypertensive rats. Vascular
      norepinephrine responses were evaluated before and after inhibition of cAMP
      dependent protein kinase [protein kinase A(PKA)] with Rp-adenosine 3',5'-cyclic
      monophosphothioate (Rp-cAMPS) or guanylate cyclase with LY-83583. Male Sprague
      Dawley rats were divided into two groups: those with portal hypertension by
      portal vein stenosis and normal controls. The small intestine was prepared for
      microcirculatory studies. Arteriolar diameter and erythrocyte velocity were
      monitored, and microvascular flow was calculated from velocity and diameter data.
      The preparation was challenged with incremental concentrations of norepinephrine
      before and after addition of Rp-cAMPS (50 microM) or LY-83583 (30 microM).
      Arteriolar diameter and blood flow were significantly elevated in portal
      hypertensive rats; norepinephrine responses were significantly depressed. LY
      83583 did not alter arteriolar diameter, blood flow, or norepinephrine
      responsiveness in normal or portal hypertensive rats. Rp-cAMPS did not affect
      arteriolar diameter, blood flow, or norepinephrine responsiveness in normal rats.
      However, in portal hypertensive rats, Rp-cAMPS reduced blood flow by
      approximately 20% (P < 0.05) and completely restored vascular norepinephrine
      responses to normal. The results indicate that cAMP- but not cGMP-dependent
      events are primarily responsible for the loss of microvascular norepinephrine
      responsiveness in portal hypertensive intestine.

PMID- 9142916
TI  - Different pathways mediate cholecystokinin actions in cholelithiasis.
AB  - Smooth muscle from gallbladders with cholesterol stones exhibits impaired
      response to cholecystokinin (CCK). This study investigated whether the impaired
      response is mediated by different signal-transduction pathways responsible for
      CCK-induced contraction in prairie dog and human gallbladders with cholesterol
      stones. Gallbladder muscle cells were isolated enzymatically to study
      contraction. Protein kinase C (PKC) activity was measured by examining the
      phosphorylation of a specific substrate peptide from myelin basic protein Ac-MBP
      (4-14). Gallbladder muscle cells from high-cholesterol-fed prairie dogs
      contracted less in response to CCK octapeptide (CCK-8) than those from the
      control group. However, inositol-1,4,5-trisphosphate (IP3), diacylglycerol, and
      guanosine 5'-O-(3-thiotriphosphate) induced the same magnitudes of contraction in
      these two groups. In control prairie dog and human gallbladders, the maximal
      contraction caused by 10(-8) M CCK-8 was blocked by the calmodulin antagonist
      CGS9343B but not by the PKC inhibitor H-7. Conversely, in gallbladders with
      cholesterol stones from prairie dogs or human patients, the maximal contraction
      induced by 10(-8) M CCK-8 was blocked by H-7 and chelerythrine but not by
      CGS9343B. In these gallbladders CCK-8 caused a significant PKC translocation from
      the cytosol to the membrane. High CCK concentrations may activate the calmodulin
      dependent pathway in functionally normal gallbladder muscle and the PKC-dependent
      pathway in muscle from gallbladders with cholesterol stones. The defect of
      gallbladder muscle after cholesterol feeding and stones might reside in the steps
      before G protein activation.

PMID- 9142917
TI  - Nitric oxide attenuates and xanthine oxidase exaggerates lung damage-induced gut
      injury.
AB  - Aspirated gastric contents can evoke multiorgan failure. We hypothesized that
      secondary intestinal epithelial dysfunction after lung damage would be mediated
      by xanthine oxidase (XO) and antagonized by endogenous gut nitric oxide (NO).
      Isosmotic saline or HCl solutions were instilled intratracheally in anesthetized
      rats, and intestinal injury was assessed 190 min later by measuring the blood-to
      lumen clearance of 51Cr-labeled EDTA (51Cr-EDTA clearance) and gut wall
      neutrophil population density. Intratracheal HCl increased 51Cr-EDTA clearance,
      and this transepithelial leak was attenuated by either systemic L-arginine or
      intraluminal NO and by chronic dietary pretreatment with allopurinol or sodium
      tungstate. Conversely, lung damage-induced gut leak was exaggerated by NO
      synthase inhibition or intravenous XO administration. Intratracheal HCl also
      increased intestinal wall neutrophil density and myeloperoxide activity. We
      conclude that two enzymatic systems involved in remote gut barrier dysfunction
      after endobronchial acidification are XO as mediator and NO synthase as
      antagonist.

PMID- 9142918
TI  - Role of plasma vasopressin as a mediator of nausea and gastric slow wave
      dysrhythmias in motion sickness.
AB  - The possible role of vasopressin in nausea and gastric dysrhythmias in motion
      sickness was tested by electrogastrography in 14 subjects during circular vection
      (60 degrees/s) and vasopressin infusion. Tachygastria was expressed as the signal
      percent >4.5 cycles/min. Vection evoked nausea scores of 2.6 +/- 0.2 (0 = none to
      3 = severe) in 10 subjects with increases in tachygastric activity (15 +/- 2 to
      45 +/- 3%) and plasma vasopressin (4.5 +/- 1.5 to 8.4 +/- 2.5 pg/ml) that were
      blocked by atropine but not indomethacin. Four asymptomatic subjects had no
      tachygastria or vasopressin release. Vasopressin at 0.2 U/min (plasma level =
      322.1 +/- 10.3 pg/ml) evoked nausea (2.6 +/- 0.4) and increases in
      tachyarrhythmic activity (41 +/- 5%) that were blunted by atropine but not
      indomethacin. There were no differences in nausea or dysrhythmias with
      vasopressin infusion in subjects who noted nausea during vection versus those who
      did not. To conclude, vection evokes nausea, dysrhythmias, and vasopressin
      release in motion sickness-susceptible humans via cholinergic prostaglandin
      independent pathways. Supraphysiological vasopressin infusions evoke nausea and
      dysrhythmias by similar pathways to equal degrees in motion sickness-susceptible
      and -resistant subjects. Thus central but not peripheral actions of vasopressin
      may contribute to nausea and slow wave disruption with vection. Blunting of both
      the release and action of vasopressin by atropine may explain its beneficial
      action in motion sickness.

PMID- 9142919
TI  - PSP expression in murine lacrimal glands and function as a bacteria binding
      protein in exocrine secretions.
AB  - Nonobese diabetic (NOD) mice, an animal model for type I autoimmune diabetes and
      autoimmune sialoadenitis, abnormally express parotid secretory protein (PSP) in
      the submandibular glands (Robinson, C. P., H. Yamamoto, A. B. Peck, and M. G.
      Humphreys-Beher. Clin. Immunol. Immunopathol. 79: 50-59, 1996). To evaluate
      possible PSP gene dysregulation in the NOD mouse, we have examined a number of
      organs and tissues for PSP mRNA transcripts and protein expression. Results
      indicate that PSP is produced in the lacrimal glands of NOD mice as well as most
      laboratory mouse strains. Although purified salivary PSP from C3H/HeJ or BALB/c
      mice fails to affect amylase enzyme activity in in vitro assays, PSP bound to
      whole bacteria in a Zn2+-dependent manner. Additionally, radiolabeled protein
      bound to specific bacterial membrane proteins using a ligand binding assay. PSP
      gene transcription, but not protein production, was observed in the heart and
      pancreas from NOD mice, indicating abnormal transcription of the PSP gene.
      Sequence analysis of PSP cDNA from NOD mice revealed numerous base differences
      (compared with the published PSP sequence) capable of leading to significant
      amino acid substitutions, suggestive of strain-specific differences for the
      protein in mice. Together these results suggest that there exists in the NOD
      mouse a dysregulation of PSP transcription in various tissues. However, except
      for C3H/HeJ mice, PSP appears as a normal product of the lacrimal glands where,
      as in saliva, it may function as a nonimmune antimicrobial agent in the
      protection of tissue surfaces exposed to the external environment.

PMID- 9142920
TI  - CFTR mediates cAMP- and Ca2+-activated duodenal epithelial HCO3- secretion.
AB  - The role of the cystic fibrosis transmembrane conductance regulator (CFTR) in
      duodenal alkaline secretion has not been directly examined. The aims of this
      series of experiments were to determine if CFTR mediates basal and stimulated
      duodenal epithelial HCO3- secretion. Utilizing the cystic fibrosis murine model
      (cftr(m1UNC)), we compared normal [CFTR(+/+)] littermates (34-46 days old) with
      CFTR(-/-) animals (34-39 days old). Anesthesia was induced and maintained with
      intraperitoneal Hypnorm-midazolam. The proximal duodenum (4-7 mm) was cannulated
      and perfused with 154 mM NaCl. Either forskolin (10(-6)-10(-4) M) or carbachol
      (10(-6)-10(-3) M) was perfused intraluminally to activate adenosine 3',5'-cyclic
      monophosphate (cAMP)- and Ca2+-mediated HCO3- secretion, respectively. Effluent
      volumes were weighed and HCO3- quantitated by back titration. Basal HCO3-
      secretion was diminished significantly (P < 0.01) in CFTR(-/-)vs. normal
      CFTR(+/+) mice (2.8 +/- 0.5 vs. 5.3 +/- 0.4 micromol x cm(-1) x h(-1)). Moreover,
      in CFTR(-/-) mice, both forskolin- and carbachol-stimulated peak HCO3- secretions
      were fourfold less compared with those in CFTR(+/+) littermates (3.7 +/- 0.2 vs.
      15.6 +/- 2.1 and 4.7 +/- 0.3 vs. 14.2 +/- 2.5 micromol x cm(-1) x h(-1),
      respectively; P < 0.01). In conclusion, CFTR plays a significant role in
      mediating basal, cAMP-, and Ca2+-activated duodenal epithelial HCO3- secretion.

PMID- 9142921
TI  - Glutamine protects intestinal epithelial cells: role of inducible HSP70.
AB  - Glutamine (Gln) protects gut mucosa against injury and promotes mucosal healing.
      Because the induction of heat shock proteins (HSP) protects cells under
      conditions of stress, we determined whether Gln conferred protection against
      stress in an intestinal epithelial cell line through HSP induction. Gln added to
      IEC-18 cells induces an increase in HSP70, a concentration-dependent effect also
      seen with mRNA. Two forms of injury, lethal heat (49 degrees C) and oxidant, were
      used, and viability was determined by 51Cr release. Gln-treated cells were
      significantly more resistant to injury. Treatment with 6-diazo-5-oxo-L-norleucine
      (DON), a nonmetabolizable analog of Gln, induced HSP70 and protected cells from
      injury, but less than Gln. These findings suggest that the effects of Gln on
      HSP70 induction and cellular protection are mediated by metabolic and
      nonmetabolic mechanisms. To determine whether HSP induction was central to the
      action of Gln and DON, quercetin, which blocks HSP induction, was used. Quercetin
      blocked HSP70 induction and the protective effect of Gln and DON. We conclude
      that the protective effects of Gln in intestinal epithelial cells are in part
      mediated by HSP70 induction.

PMID- 9142923
TI  - Constitutive NOS isoforms account for gastric mucosal NO overproduction in uremic
      rats.
AB  - To study whether renal failure enhances gastric mucosal nitric oxide (NO)
      formation in the rat, we measured 1) in vivo NO concentration and 2) NO synthase
      (NOS) activity, content, and mRNA expression in gastric mucosal homogenates of
      uremic and sham-operated anesthetized rats. Gastric mucosal NO release was
      measured by an electrochemical technique. NOS content was analyzed by Western
      immunoblots, using specific monoclonal antibodies. Constitutive (Ca2+ dependent;
      cNOS) and inducible (Ca2+ independent; iNOS) NOS activities were assayed by
      following the conversion of L-[U-14C]arginine to [U-14C]citrulline. mRNA
      expression for the constitutive neuronal (ncNOS), endothelial (ecNOS), and iNOS
      isoforms was determined by reverse transcription-polymerase chain reaction. Under
      basal conditions, gastric mucosal NO concentration was significantly greater in
      uremic compared with control rats. This was accompanied by significantly greater
      gastric mucosal cNOS activity in uremic rats than in control rats, whereas no
      differences were observed in iNOS activity between both groups of animals.
      Moreover, total enzyme content and the levels of gastric mucosal mRNA expression
      for ncNOS, ecNOS, and iNOS showed no significant differences between uremic and
      sham-operated rats. These data confirm that, in uremic rats, enhanced Ca2+
      dependent NOS activity is responsible for gastric mucosal NO overproduction and
      suggest that the main regulatory mechanism is not transcriptional but
      translational and/or posttranslational in nature.

PMID- 9142922
TI  - Cytokine regulation of fibroblast growth factor receptor 3 IIIb in intestinal
      epithelial cells.
AB  - Proliferation and function of the intestinal epithelium is modulated by a range
      of regulatory peptides, including cytokines and peptide growth factors. To define
      mechanisms integrating these regulatory systems, the effects of growth factors
      and cytokines on the expression of the fibroblast growth factor (FGF) receptor 3
      (FGFR3) IIIb expressed on intestinal epithelial cells were examined in Caco-2
      cells. Regulated expression of FGFR3 IIIb was associated with acquisition of the
      differentiated state. Keratinocyte growth factor (KGF), a ligand of another
      member of the FGF receptor family, enhanced expression of FGFR3 IIIb, but acidic
      FGF, the ligand for FGFR3 IIIb itself, had no effect. Epidermal growth factor and
      transforming growth factor-beta also markedly enhanced FGFR3 IIIb expression in a
      different temporal pattern. In addition, FGFR3 IIIb expression was increased 10
      fold by the cytokine interleukin-2. These studies demonstrate integration between
      cytokines and growth factor ligand-receptor systems in intestinal epithelial
      cells.

PMID- 9142924
TI  - Sumatriptan, a selective 5-HT1 receptor agonist, induces a lag phase for gastric
      emptying of liquids in humans.
AB  - Sumatriptan, a 5-hydroxytryptamine1 (5-HT1) receptor agonist at enteric neuronal
      5-HT receptors, causes a relaxation of the gastric fundus and inhibition of
      antral contractile activity. The present study examined the effect of sumatriptan
      on gastric emptying of solids and liquids in humans. In eight healthy subjects
      the gastric emptying rate for liquids and solids was measured using the carbon
      labeled glycine and octanoic acid breath test after subcutaneous administration
      of placebo or sumatriptan. Sumatriptan increased the gastric half-emptying time
      of liquids (P < 0.0005) and induced a prolonged lag phase for liquids (P <
      0.0005) in all subjects. Sumatriptan increased gastric half-emptying time (P <
      0.005) and the lag phase of solids (P < 0.05) in all subjects. In two healthy
      subjects gastric emptying of liquids and solids after subcutaneous administration
      of sumatriptan was studied by radioscintigraphy. Radioscintigraphy confirmed the
      delayed emptying and the prolonged lag phases after sumatriptan. In conclusion,
      sumatriptan delays gastric emptying of solids and liquids in healthy subjects.
      Moreover, sumatriptan induces a lag phase for liquids. The mechanism by which
      sumatriptan alters gastric emptying remains to be studied.

PMID- 9142925
TI  - A new method to measure gastric emptying in conscious dogs: a validity study and
      effects of EM523 and L-NNA.
AB  - A new method for measurement of gastric emptying without the use of radioisotope
      markers has been developed in dogs. A test meal was given after measurement of
      its freeze-dried weight, and 1-ml duodenal samples were collected through an
      indwelling tube at 15-min intervals, and their absolute weight was measured. The
      duodenum was continuously perfused with phenolsulfonphthalein to determine the
      recovery of each sample. Three different calorie or fat-enriched meals were
      administered with 100 ml saline containing polyethylene glycol as a liquid
      marker. The results showed that increasing the calorie load of, and adding fat
      to, the test meal proportionally delayed gastric emptying of the solid phase.
      Utilizing this method, it was found that EM523, an erythromycin derivative,
      accelerated the gastric emptying of solids, whereas N(omega)-nitro-L-arginine (L
      NNA) markedly delayed the gastric emptying of both solids and liquids. In
      conclusion, this freeze-drying method is a reliable technique for measuring the
      gastric emptying of the solid phase in dogs.

PMID- 9142926
TI  - Rhythmic oscillating complexes in gastrointestinal tract of chickens: a role for
      motilin.
AB  - Rhythmic oscillating complex (ROC) is a highly organized gastrointestinal
      motility pattern recently described in fasted avian species. ROCs show several
      high-speed aborad-propagated contractions that progressively change into others
      of orad direction. In addition, chickens show migrating motor complexes (MMC) in
      both fed and fasting states. Recently, motilin was isolated and characterized
      from chicken small intestine. Accordingly, the aim of this study was to learn
      whether chicken motilin might be involved in either ROC or MMC induction.
      Electromyographic recordings were obtained from different areas of the
      gastrointestinal tract of chickens while motilin was infused. The response to
      chicken motilin was dose dependent in both fed and fasted animals; a bolus of 4 x
      10(-11) mol/kg (n = 5) did not modify the intestinal motor pattern, whereas 4 x
      10(-10) and 4 x 10(-9) mol/kg (n = 5 each) induced a complete ROC pattern of 5.2
      +/- 0.6 and 10.8 +/- 0.9 min, respectively. ROCs induced by chicken motilin
      presented exactly the same pattern as that described during a spontaneous ROC.
      Furthermore, motilin concentration in plasma, measured by radioimmunoassay,
      increased during a spontaneous ROC. This study suggests that chicken motilin
      triggers an ROC in chickens. The fact that plasma motilin levels increased during
      spontaneous ROC strongly suggests that motilin is involved in the induction of
      the ROC pattern. Motilin seems to play a different role in avian and mammalian
      species, because a phase III of the MMC was never induced by motilin infusion.

PMID- 9142927
TI  - Effects of phospholipase A2, 12-lipoxygenase, and cyclooxygenase inhibitors in
      the feline pulmonary bed.
AB  - The effects of phosphonofluoridic acid, methyl-5,8,11,14-eicosatetraenyl ester
      (MAFP), a phospholipase A2 inhibitor, on pressor responses to angiotensin II (ANG
      II), norepinephrine (NE), serotonin (5-HT), the calcium channel opener BAY K
      8644, and the thromboxane A2 mimic U-46619 were studied in the pulmonary vascular
      bed of the intact-chest cat. Under conditions of constant lobar blood flow,
      injections of ANG II, NE, 5-HT, U-46619, and BAY K 8644 into the lobar arterial
      perfusion circuit caused dose-related increases in lobar arterial pressure that
      were reproducible with respect to time. Infusion of MAFP into the perfused lobar
      artery at doses of 100 to 300 microg/kg for 10 min significantly reduced
      vasoconstrictor responses to ANG II; however, the phospholipase A2 inhibitor did
      not alter vasoconstrictor responses to BAY K 8644, 5-HT, NE, or U-46619. The
      combination of the higher dose of the phospholipase A2 inhibitor MAFP with the
      phospholipase C inhibitor U-73122 significantly affected vasoconstrictor
      responses to ANG II, NE, and 5-HT but not to BAY K 8644. In a separate series of
      animals, the effects of a lipoxygenase inhibitor, baicalein, were investigated.
      Infusion of baicalein into the perfused lobar artery at doses of 100 microg/kg
      for 10 min significantly reduced vasoconstrictor responses to ANG II but not the
      vasoconstrictor responses to BAY K 8644, 5-HT, NE, or U-46619. In a final series
      of experiments, the effects of a cyclooxygenase inhibitor, meclofenamate, were
      investigated, and intravenous injection of the meclofenamate at a dose of 2.5
      mg/kg did not significantly affect vasoconstrictor responses to ANG II, 5-HT, BAY
      K 8644, NE, or U-46619. These data provide support for the hypothesis that
      pulmonary vasopressor responses to ANG II are mediated, in part, by the
      activation of phospholipase A2, phospholipase C, and the lipoxygenase pathway in
      the pulmonary vascular bed of the cat.

PMID- 9142928
TI  - Increased cAMP levels in stimulated neutrophils inhibit their adhesion to human
      bronchial epithelial cells.
AB  - Bronchial epithelial cells express the intercellular adhesion molecule-1 that
      mediates binding of activated neutrophils via interaction with Mac-1 and/or
      leukocyte function-associated antigen-1. In this study, we examined whether
      increased intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP)
      affected neutrophil adhesion to the human bronchial epithelial cells. It was
      found that the N-formylmethionyl-leucyl-phenylalanine (fMLP)-stimulated
      neutrophil adhesion was concentration dependently inhibited when the cAMP analogs
      dibutyryl adenosine 3',5'-cyclic monophosphate or 8-bromoadenosine 3',5'-cyclic
      monophosphate were present. The beta-adrenergic receptor agonists isoprenaline
      and salmeterol, in the presence of the phosphodiesterase inhibitor 3-isobutyl-1
      methylxanthine (IBMX), were also able to inhibit the fMLP-stimulated adhesion of
      neutrophils to bronchial epithelial cells. These agonists in combination with
      IBMX significantly increased the intracellular cAMP level in both neutrophils and
      epithelial cells. Preincubation of neutrophils with the long-acting beta2
      adrenergic receptor agonist salmeterol (in the presence of IBMX) inhibited their
      fMLP-stimulated adhesion to epithelial cells, whereas pretreatment of epithelial
      cells did not influence the adhesion process. When ethanol-fixed epithelium was
      used, salmeterol pretreatment also diminished the adhesion of stimulated
      neutrophils. Moreover, combinations of salmeterol or isoprenaline with IBMX
      inhibited fMLP-upregulated Mac-1 expression. Therefore, we conclude from these
      data that elevation of intracellular cAMP in the neutrophil inhibits stimulated
      neutrophil adhesion to bronchial epithelial cells via Mac-1.

PMID- 9142929
TI  - Nitric oxide inhibits ACh-induced intracellular calcium oscillations in porcine
      tracheal smooth muscle.
AB  - With real-time confocal microscopy, the effect of three nitric oxide (NO) donors,
      S-nitroso-N-acetylpenicillamine, S-nitrosoglutathione, and diethylamine NO
      adduct, on the dynamic intracellular Ca2+ concentration ([Ca2+]i) response of
      porcine tracheal smooth muscle (TSM) cells to acetylcholine (ACh) was examined.
      ACh initiated propagating [Ca2+]i oscillations in TSM cells, which were inhibited
      by NO donors. 8-Bromoguanosine 3',5'-cyclic monophosphate slowed the frequency of
      [Ca2+]i oscillations but did not completely inhibit oscillations, suggesting that
      the effects of NO donors are only partially mediated via guanosine 3',5'-cyclic
      monophosphate-dependent mechanisms. After preexposure to NO donors, ACh induced a
      small biphasic [Ca2+]i response that was blocked by nifedipine, suggesting a lack
      of effect on Ca2+ influx through voltage-gated channels. In addition, NO donors
      did not inhibit Ca2+ influx induced by BAY K 8644. The [Ca2+]i response to
      caffeine was inhibited by NO donors, indicating inhibition of sarcoplasmic
      reticulum (SR) Ca2+ release. When Ca2+ influx and SR Ca2+ reuptake were blocked,
      basal [Ca2+]i increased, and this was inhibited by NO donors, suggesting enhanced
      Ca2+ efflux. These results indicate that NO donors inhibit [Ca2+]i oscillations
      by blocking SR Ca2+ release and enhancing Ca2+ extrusion.

PMID- 9142930
TI  - Sickle erythrocytes induce prostacyclin and thromboxane synthesis by isolated
      perfused rat lungs.
AB  - The role of eicosanoids in the pathogenesis of acute or chronic lung syndrome in
      sickle cell disease is unknown. We investigated the synthesis of prostacyclin
      (PGI2), thromboxane (Tx) A2, and prostaglandin (PG) E2 by three groups of
      isolated rat lungs perfused with buffer (GPBS), normal (HbAA), and sickle (HbSS)
      erythrocyte suspensions. Isolated lungs were perfused at a constant pressure and
      flow rate (Q) of 40 ml x kg(-1) x min(-1) with GPBS or 7% erythrocyte suspensions
      for 15 min. Autologous platelet-rich plasma (PRP) was added, and perfusion was
      continued for 15 min and then at two times Q for another 15 min. Perfusate
      samples were assayed for the specific eicosanoids. Perfusate level of PGI2 in
      GPBS lungs was the least among the three groups. However, the PGI2 level in HbSS
      lungs was 90% higher than from HbAA lungs after 15 min of perfusion and was 180%
      higher on perfusion with PRP. Additionally, coperfusion of erythrocytes and PRP
      augmented perfusate levels of TxA2 and PGE2 over 1,000% more in HbSS than
      HbAAlungs. These data show that HbSS erythrocytes increased perfusate levels of
      the eicosanoids, suggesting increased synthesis, perhaps due to aberrant
      erythrocyte-endothelium interactions.

PMID- 9142931
TI  - Qualitative immunoblot analysis of PKC isoforms expressed in airway smooth
      muscle.
AB  - Protein kinase C (PKC) was originally identified as a single serine/ threonine
      protein kinase with calcium- and phospholipid-dependent activity, but more
      recently PKC has been found to consist of a family of multiple isoenzymes with
      different biochemical characteristics, substrates, and cofactor requirements. PKC
      is particularly important in regulating airway smooth muscle (ASM) tone. Although
      a previous investigation has demonstrated PKC-beta, -delta, -epsilon, -theta and 
      zeta in canine trachealis muscle, additional PKC isoforms have not been
      characterized in ASM. Therefore, immunoblot analysis using nine isotype-specific
      antibodies was used to further characterize the expression of PKC isoforms in
      porcine ASM. In addition to the previously described beta-, delta-, epsilon-, and
      zeta-isoforms in ASM, the calcium-dependent alpha-isoform, and the calcium- and
      diacylglycerol-independent isoforms iota/lambda and mu were identified. This
      study demonstrates multiple PKC isoforms in porcine ASM that can participate in
      intracellular signaling pathways in this tissue.

PMID- 9142933
TI  - Endothelin-A receptor antagonist BQ-610 blocks cigarette smoke-induced
      mitogenesis in rat airways and vessels.
AB  - To ascertain whether endothelin may play a role in cigarette smoke-induced cell
      proliferation in the airways and arterial vasculature of the lung, we exposed
      groups of seven Sprague-Dawley rats to either room air (control) plus saline
      infusion, an intravenous infusion of the selective endothelin A antagonist BQ-610
      (control BQ-610), the smoke of 10 cigarettes (smoke only), or the smoke of 10
      cigarettes after intravenous BQ-610 infusion (smoke + BQ-610). Cell proliferation
      was quantified by determining the percentage of cell nuclei labeled by 5-bromo-2'
      deoxyuridine. We separately evaluated the cells in the epithelium and wall
      components of the bronchioles, and endothelium and wall components of the
      peribronchiolar and perialveolar ductular arteries. We found that cigarette smoke
      produced significant cell proliferation in the airway epithelium and wall, in the
      peribronchiolar arterial endothelial compartment, and in both the endothelial and
      wall compartments of the perialveolar ductular arteries. Pretreatment with BQ-610
      reduced the peribronchiolar arterial endothelial and the perialveolar ductular
      arterial wall proliferation to control lev- els and reduced but did not totally
      abrogate the smoke-in- duced proliferation of the airway epithelial, airway wall,
      and perialveolar ductular arterial endothelial compartments. We conclude that
      cigarette smoke-induced cell proliferation of the airways and pulmonary arterial
      vessels is at least partially mediated through stimulation of the endothelin-A
      receptors.

PMID- 9142932
TI  - Activation of endothelial cell phospholipase D by polycations.
AB  - Naturally occurring polycations and cationic proteins are implicated in vascular
      disorders. It is known that activated leukocytes and platelets release
      polycations, such as polylysine (PLys), of varying molecular sizes into the
      vasculature, and some of these have been described to be bactericidal.
      Polycations interact with endothelial cells (ECs) and cause alterations in
      permeability and cellular functions. The precise mechanism(s) by which
      polycations bring about cellular changes is unknown. Here, we report that the
      polycations PLys and polyarginine (PArg) induce phospholipase D (PLD) activation
      in ECs. Polycation-mediated PLD activation was both time and concentration
      dependent, and activation of PLD was not due to cytotoxicity. PArg was more
      potent compared with PLys of the same molecular weight in stimulation of PLD.
      Treatment with bisindolylmaleimide, a specific protein kinase C (PKC) inhibitor,
      and heparin attenuated polycation-mediated PLD activation. Furthermore,
      downregulation of PKC by 12-O-tetradecanoylphorbol-13-acetate (100 nM, 18 h) also
      blocked polycation-mediated PLD stimulation. These data suggest that polycation
      mediated PLD stimulation probably involves PKC and may represent an important
      cellular response to leukocyte/platelet activation in the vascular endothelium.

PMID- 9142934
TI  - Regulated stimulation of epithelial cell DNA synthesis by fibroblast-derived
      mediators.
AB  - Interactions of interstitial fibroblasts with nearby epithelial cells are thought
      to play a role in lung growth and development. The present studies support this
      premise. Medium conditioned by second-passage lung fibroblasts (FCM) stimulated
      both DNA synthesis and accumulation in low-density (2 x 10(4)/cm2) cultures of
      type II alveolar epithelial cells. FCM effects did not require serum; they were
      time- and dose dependent, with half-maximal FCM activity at 1:8 dilution. A
      maximal response to FCM required 30 h of exposure. FCM activity was reduced in
      medium from fibroblasts treated with dexamethasone, suggesting physiological
      regulation. Type II cells subjected to cyclic mechanical stress demonstrated an
      increased response to FCM compared with static cultures. FCM activity did not
      appear to be accounted for by hepatocyte growth factor, keratinocyte growth
      factor, acidic fibroblast growth factor, or fibronectin. These results suggest
      that early passage lung fibroblasts release, by regulated pathways, one or more
      factors that stimulate DNA synthesis by type II cells. Sensitivity to FCM appears
      to be elevated in type II cell cultures subjected to cyclic mechanical stress.

PMID- 9142935
TI  - Nitric oxide attenuates lung endothelial injury caused by sublethal hyperoxia in
      rats.
AB  - Inhaled nitric oxide (NO) has been shown to prevent oxidant-induced lung injury
      in isolated-perfused lung models, whereas NO-derived oxidants may contribute to
      acute lung injury secondary to hyperoxia. Whether inhaled NO improves or
      contributes to oxidant-mediated lung injury may depend on the timing of NO
      administration or how lung injury is assessed. The objective of these studies was
      to determine whether inhaled NO (20 ppm) was protective or harmful to the
      different lung barriers when it was administered with 95% O2 for 60 h in Sprague
      Dawley rats by measuring fluid transport and permeability to protein across the
      lung endothelium and the alveolar epithelium. Inhaled NO significantly attenuated
      the O2-mediated lung endothelial injury and abolished the increase in the
      bronchoalveolar lavage fluid content of rTI40, a specific and sensitive marker of
      alveolar epithelial type I cell injury, that occurs secondary to hyperoxia. In
      conclusion, inhaled NO administered with high concentrations of O2 may protect
      the lung endothelium and the alveolar epithelium against O2-mediated injury.

PMID- 9142936
TI  - Contribution of PKC to beta-hexosaminidase-induced airway smooth muscle
      proliferation.
AB  - beta-Hexosaminidases (Hex) A and B promote mitogenesis via airway smooth muscle
      (ASM) mannose receptor. The objective of this study was to elucidate the
      contribution of protein kinase C (PKC) in Hex-induced mitogenesis in ASM cells
      (ASMC). Exposure of ASMC to Hex caused increases in both the calcium-dependent
      and the calcium-independent PKC activities. Both downregulation of PKC and PKC
      inhibitors staurosporine and calphostin C diminished Hex-induced DNA synthesis
      and cell number. Hex-induced DNA synthesis was enhanced by a diacylglycerol
      kinase inhibitor, R-59022, which was blocked by calphostin C. These data suggest
      that activation of PKC in part mediates Hex-induced mitogenesis in ASMC.

PMID- 9142937
TI  - TNF-alpha inhibits isoproterenol-stimulated adenylyl cyclase activity in cultured
      airway smooth muscle cells.
AB  - Inflammation, increased cytokine production, and decreased responsiveness of
      airway smooth muscle (ASM) to beta-adrenergic agonists are characteristics of
      asthma. We questioned whether the cytokine tumor necrosis factor-alpha (TNF
      alpha) directly impaired beta-adrenergic signal transduction in cultured canine
      ASM cells. Confluent ASM cells exposed to TNF-alpha (0.1-10 ng/ml) for 72 h
      showed lower maximal levels of adenylyl cyclase activity in response to
      isoproterenol (10 ng/ml; 14 +/- 4.3 vs. 7.5 +/- 1.3 pmol adenosine 3',5'-cyclic
      monophosphate x well(-1) x 20 min(-1), control vs. treated, respectively),
      despite no changes in beta-adrenergic receptor numbers (maximum number of binding
      sites = 4.8 +/- 0.72 vs. 4.5 +/- 0.81 fmol/mg protein, control vs. treated,
      respectively). Adenylyl cyclase activities in response to prostaglandin E1, NaF,
      or forskolin were not different in treated and untreated cells. These results
      demonstrate that a cytokine known to be increased during exacerbation of
      asthmatic symptoms directly impairs beta-adrenergic function in ASM cells and
      suggests a mechanism by which inflammation impairs beta-adrenergic receptor
      signal transduction in asthma.

PMID- 9142938
TI  - Nitric oxide as an inflammatory mediator of radiation pneumonitis in rats.
AB  - Radiation pneumonitis is a major complication of radiation therapy. To elucidate
      the mechanisms of radiation-induced pneumonitis, we studied nitric oxide (NO)
      produced from lung tissues using a model of unilaterally irradiated rats. Our
      results demonstrated that alveolar macrophages (AM) produced NO after
      irradiation, and the expression of inducible NO synthase (NOS) in both AM and
      alveolar epithelial cells was increased. Furthermore, the progression of
      radiation pneumonitis was reduced with the in vivo treatment of the NOS inhibitor
      N(G)-nitro-L-arginine methyl ester (L-NAME). The effect of L-NAME was further
      confirmed by the inhibition of mRNA expression for procollagen-alpha1 type III of
      the lung. With these results, NO produced from AM and alveolar epithelial cells
      after irradiation may be an important mediator in the progression of radiation
      pneumonitis.

PMID- 9142939
TI  - Role of ryanodine receptor channels in Ca2+ oscillations of porcine tracheal
      smooth muscle.
AB  - Acetylcholine (ACh) induces repetitive, propagating intracellular Ca2+
      concentration ([Ca2+]i) oscillations in porcine tracheal smooth muscle (TSM)
      cells. Using real-time confocal microscopy, we examined the role of sarcoplasmic
      reticulum (SR) Ca2+ release through inositol 1,4,5-trisphosphate (IP3) receptor
      and ryanodine receptor (RyR) channels in ACh-induced [Ca2+]i oscillations. In
      beta-escin permeabilized TSM cells, exposure to ACh in the presence of GTP also
      resulted in [Ca2+]i oscillations. [Ca2+]i oscillations could not be initiated by
      IP3 alone; however, an elevation of [Ca2+]i was observed. During ongoing [Ca2+]i
      oscillations, exposure to heparin, an IP3 receptor antagonist, caused a slowing
      of oscillation frequency but not complete inhibition. In contrast, ruthenium red,
      a RyR antagonist, completely abolished ACh-induced [Ca2+]i oscillations. Reverse
      transcriptase-polymerase chain reaction of TSM mRNA demonstrated the expression
      of RyR-2 and RyR-3 isoforms of the RyR. These results indicate that SR Ca2+
      release through RyR channels is critical for ACh-induced [Ca2+]i oscillations in
      porcine TSM cells.

PMID- 9142940
TI  - Developmental changes of fetal rat lung Na-K-ATPase after maternal treatment with
      dexamethasone.
AB  - Late in gestation, the prenatal fetal alveolar epithelium switches from fluid
      secretion to resorption of salt and water via apical sodium channels and basal Na
      K-ATPase. The amounts of lung sodium pump activity protein and mRNA increase in
      the lung just before birth. Because maternal glucocorticoids (GC) may promote
      maturation of the alveolar epithelium and augment fetal surfactant apoprotein
      levels, we hypothesized that GC increase the fetal lung Na-K-ATPase alpha- and
      beta-subunit gene expression in development. Timed-pregnant Sprague-Dawley rats
      were injected daily with intraperitoneal dexamethasone (1 mg/kg) or saline for 1,
      3, or 5 days before death at fetal day (FD) 17 or 19. Maternal GC treatment
      altered the fetal lung wet to dry weight, decreasing it at FD17 and increasing it
      at FD19. Northern analysis of total lung RNA for the alpha1- and beta1-pump
      subunits demonstrated differential regulation of the mRNA in response to GC. At
      FD17, beta1-mRNA increased after 1 (FD16) or 3 days (FD14-FD16) of GC treatment,
      whereas alpha1-mRNA was not altered. There were accompanying increases in beta1-,
      but not alpha1-, protein. At FD19, GC treatment for 5 days (FD14-FD18) increased
      beta1- and decreased alpha1-mRNA levels, but treatment for 1 (FD18) or 3 days
      (FD16-FD18) had no effect. In all groups, the alpha1-Na-K-ATPase protein was
      predominantly on the basolateral surface of airspace epithelium by
      immunofluorescence. In summary, maternal dexamethasone differentially affected
      the fetal lung mRNA levels of the two sodium pump subunits in a complex manner,
      with increased beta1-mRNA levels dependent on duration of treatment and fetal
      age.

PMID- 9142941
TI  - Pulmonary endothelial thiazine uptake: separation of cell surface reduction from
      intracellular reoxidation.
AB  - The objective of this study was to further evaluate the hypothesis that the
      accumulation of thiazine dyes, such as methylene blue, by cultured bovine
      pulmonary arterial endothelial cells involves reduction on the cell surface,
      followed by diffusion of the lipophilic reduced form of the dye into the cells
      and intracellular reoxidation to the relatively membrane-impermeant hydrophilic
      form. The specific question addressed was whether inhibition of methylene blue
      uptake by cyanide and azide is via inhibition of extracellular reduction or
      inhibition of intracellular reoxidation. We used the cell membrane-impermeant
      ferricyanide ion as a secondary electron acceptor to measure the extracellular
      reduction of methylene blue independently from its uptake by the cells. In
      addition, toluidine blue O, incorporated into an acrylamide polymer so that it
      could not permeate the cells in either its reduced or oxidized forms, was used to
      examine the effects of cyanide and azide on the extracellular reduction.
      Microscopic observations of the effect of the inhibitors on the intracellular
      accumulation of methylene blue were also made. The results indicate that the
      reduction and intracellular sequestration are separate processes and that, in
      doses that inhibited intracellular reoxidation, and therefore uptake and
      sequestration, neither cyanide nor azide had an inhibitory effect on
      extracellular reduction. The intracellular distribution of the observable
      oxidized form of the dye was consistent with oxidation of the reduced dye within
      subcellular organelles. The demonstration that extracellular reduction and
      intracellular sequestration are separate events is consistent with the
      hypothesized sequence of events.

PMID- 9142942
TI  - KGF prevents hydrogen peroxide-induced increases in airway epithelial cell
      permeability.
AB  - Keratinocyte growth factor (KGF) has recently been shown to protect rats from
      hyperoxia-induced lung injury. However, the mechanism of the protective effect of
      KGF remains unclear. To elucidate the mechanism of action of KGF, we determined
      the effect of KGF on the barrier function of epithelial monolayers exposed to
      H(2)O(2). Calu-3 (human airway epithelial cells) were grown on Transwell
      membranes, and the permeability to fluorescein isothiocyanate-albumin was
      measured. Exposure to 0.5 mM H(2)O(2) significantly increased permeability from
      1.50 +/- 0.09 to 24.8 +/- 1.5 (mean +/- SE x 10(-6) cm/s; P < 0.001). Incubation
      of monolayers with 50 ng/ml KGF for 24 h significantly reduced basal albumin flux
      (0.85 +/- 0.09; P < 0.001), and pretreatment with KGF completely abolished the
      H(2)O(2)-induced permeability increase (1.08 +/- 0.09). The protective effect of
      KGF was dose dependent and was observed at concentrations as low as 1 ng/ml.
      Partial amelioration of the H(2)O(2)-induced permeability increase occurred after
      1 h of exposure to KGF. Treatment of cells with calphostin C, an inhibitor of
      protein kinase C (PKC), had no effect on the permeability of control or H(2)O(2)
      treated cells. Calphostin C abolished both the KGF-mediated decrease in basal
      albumin flux and the protective effect of KGF against H(2)O(2)-induced increases
      in permeability. KGF pretreatment also prevented H(2)O(2)-induced disruption of F
      actin staining patterns, suggesting stabilization of the cytoskeleton. These
      studies demonstrate that KGF decreases albumin flux across airway epithelial
      monolayers and prevents H(2)O(2)-induced increases in permeability by a PKC
      dependent process that may involve stabilization of the cytoskeleton.

PMID- 9142943
TI  - Most basal I(SC) in Calu-3 human airway cells is bicarbonate-dependent Cl-
      secretion.
AB  - Serous cells secrete antibiotic-rich fluid, but secretion is impaired in cystic
      fibrosis. We are investigating Calu-3 cells as a serous cell model. Basal short
      circuit current (I[SC]) in Calu-3 cells grown at air interface had a basal I(SC)
      approximately six times larger than submerged cultures (69 +/- 22 vs. 11 +/- 10
      microA/cm2). Basal I(SC) in either condition was reduced only 7 +/- 5% by
      bumetanide and was unaffected by apical amiloride, 4,4'-diisothiocyanostilbene
      2,2'-disulfonic acid, 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS), or
      calixarene but was reduced 77 +/- 18% by N-phenylanthranilic acid. Three
      transport mechanisms accounted for almost all basal I(SC). The largest component
      is HCO3(-)-dependent Cl- secretion. Replacement of Krebs-Henseleit solution with
      N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-buffered solution and
      changing gassing from 95% O2-5% CO2 to air reduced the basal I(SC) by 61 +/- 10%.
      Acetazolamide decreased basal I(SC) by 33 +/- 6%, whereas acetazolamide +
      basolateral DNDS eliminated 42-58% of the bumetanide-insensitive basal I(SC).
      Neither DNDS nor acetazolamide had any effect when applied in HCO3(-)-free
      solution. Apical phlorizin, a blocker of Na+-glucose cotransport, eliminated one
      half of the remaining I(SC). Cl- replacement with gluconate eliminated all I(SC)
      except the phlorizin-sensitive component. Unlike basal I(SC), 80 +/- 24% of
      stimulated I(SC) was inhibited by bumetanide. Thus basal and stimulated
      secretions are mediated by different mechanisms.

PMID- 9142944
TI  - Pulmonary mechanical and immunologic dysfunction in a murine model of AIDS.
AB  - Human immunodeficiency virus-infected patients occasionally exhibit alveolar
      septal wall thickening and decreases in gas diffusion capacity, but the mechanism
      underlying these abnormalities is unknown. The present study evaluated septal
      wall thickness and gas exchange properties in a murine model of the acquired
      immunodeficiency syndrome and determined whether there were alterations in lung
      lymphocyte deposition and activation that could contribute to changes in
      respiratory structure and function. Although alveolar septal wall thickness did
      not differ from control at 1, 2, and 4 wk postimmunosuppressive virus infection,
      at 8 wk after infection, septal wall thickness was substantially increased.
      Immunohistochemical evaluation at this time revealed marked increases in the
      septal wall deposition of fibronectin and collagen type IV. Pulmonary function
      tests on anesthetized mice with virus-induced septal wall thickening demonstrated
      that, although total lung capacity, compliance, and functional residual capacity
      were unaltered, diffusion capacity for carbon monoxide was significantly
      impaired. A diffuse nonspecific interstitial pneumonitis was present in lungs of
      immunodeficient mice, and flow cytometry indicated that both lymphocytes and
      macrophages were activated. Reverse transcriptase-polymerase chain reaction
      analysis of lung lymphocytes demonstrated enhanced mRNA expression for several
      cytokines known to affect lung structure. These results show that impaired gas
      exchange occurs in a murine model of acquired immunodeficiency syndrome and
      suggest that such alterations may be mediated by elaboration of cytokines from
      activated lung lymphocytes and macrophages.

PMID- 9142946
TI  - RNA in polysomes is an inhibitor of manganese superoxide dismutase RNA-binding
      protein activity.
AB  - A redox-sensitive protein in rat lung binds to the 3'-untranslated region (3'
      UTR) of manganese superoxide dismutase (Mn-SOD) mRNA; the activity of this Mn-SOD
      RNA-binding protein (Mn-SOD-BP) is greater in 12,000-g supernatant fractions
      (S12) from neonates than in S12 from adults (H. Fazzone, A. Wangner, and L. B.
      Clerch. J. Clin. Invest. 92: 1278-1281, 1993). To determine the mechanism
      underlying this developmental difference, lung subcellular fractions were tested
      for their effect on Mn-SOD-BP activity. Protein in the 130,000-g supernatant
      (S130) of lung extracts bound the 3'-UTR. However, the developmental difference
      in binding was not present in S130. The 130,000-g pellet (P130) did not bind the
      3'-UTR; rather, it contained an inhibitor of Mn-SOD-BP activity. Addition of P130
      to S130 decreased RNA binding in a dose-dependent manner. Furthermore, adult P130
      was a more potent inhibitor of RNA-binding activity than neonatal P130. These
      data indicate that the developmental difference in Mn-SOD-BP activity is due, in
      part, to an inhibitor in P130. Biochemical characterization revealed that the
      inhibitor is an RNA that may participate in the posttranscriptional control of Mn
      SOD gene expression.

PMID- 9142945
TI  - Endogenous nitric oxide limits cytokine-induced damage of murine lung epithelial
      cells.
AB  - This study investigated whether endogenous nitric oxide (NO) limits cytokine
      induced damage to the murine lung epithelial cell line LA-4. NO production was
      assessed as nitrite using the Griess reaction, and cell damage was assessed using
      ethidium homodimer-1. Cytotoxicity was first detected after a 24-h incubation
      with a combination of tumor necrosis factor-alpha, interleukin-1beta, and
      interferon-gamma (cytomix). Nitrite production increased to 78.0 +/- 0.5
      nmol/10(6) cells at 24 h. Coincubation of LA-4 with cytomix and NO synthase
      inhibitors, aminoguanidine (3-1,000 microM) and N(G)-monomethyl-L-arginine (10
      1,000 microM), but not N(G)-monomethyl-D-arginine, or a soluble guanylate cyclase
      inhibitor, 1H-[1,2,4] oxadiazole [4,3-a] quinoxalin-1-one, reduced cytomix
      induced nitrite production and increased cytotoxicity up to twofold (24 h).
      Removal of L-arginine from the medium increased damage; reintroduction of 1,000
      microM L-arginine, but not D-arginine, reversed this. In aminoguanidine-treated
      cells, replacement of NO with an NO donor, S-nitrosoglutathione (30 microM),
      reversed, in part, the cell damage observed in aminoguanidine/cytomix-treated
      cells. These results suggest that endogenous NO limits cytokine-induced lung
      epithelial damage.

PMID- 9142947
TI  - Changes in surfactant protein gene expression in a neonatal rabbit model of
      hyperoxia-induced fibrosis.
AB  - Lung injuries, including bronchopulmonary dysplasia, alter the surfactant system.
      We developed a newborn rabbit model of acute, followed by chronic, hyperoxic
      injury to study surfactant protein (SP) gene expression. Initial litters were
      exposed to >95% O2 until 50% died (LD50; 7-11 days old). Subsequent litters were
      exposed to >95% O2 for 8 days, followed by 60% O2 until 22-36 days. Controls were
      exposed to room air. LD50 animals displayed acute pulmonary inflammation, edema,
      protein leak, and surfactant dysfunction. These changes resolved, and fibrosis
      developed by 22 days. Whole lung SP-A mRNA expression (measured by membrane
      hybridization) was twice control levels at 4 days of >95% O2, with specific
      elevations in terminal bronchioles and type II cells at 4 days and the LD50 by in
      situ hybridization. Whole lung SP-B and SP-C mRNA were unchanged from control
      throughout exposure. However, in situ hybridization showed elevations in SP-B and
      SP-C mRNA in type II cells in inflamed areas at the LD50. SP mRNA alterations
      resolved by 22-36 days. The surfactant system recovers from acute hyperoxic
      injury, despite continued 60% O2 exposure.

PMID- 9142948
TI  - Localization of cholinergic nerves in lower airways of guinea pigs using antisera
      to choline acetyltransferase.
AB  - Primary antiserum to choline acetyltransferase (ChAT), a specific marker for
      cholinergic nerves, was used to characterize the distribution of cholinergic
      nerve fibers and nerve cell bodies in guinea pig airways. ChAT immunoreactive
      nerve fibers were localized to the smooth muscle throughout the conducting
      airways and in the lamina propria of the trachea and large bronchi. Likewise, all
      nerve cell bodies in the ganglia intrinsic to the trachea and bronchi displayed a
      cholinergic phenotype. By contrast, ChAT immunoreactive nerve fibers were
      infrequently seen in the lamina propria of the peripheral airways and were absent
      in the airway epithelium. No evidence for colocalization of ChAT and the enzyme
      synthesizing the putative relaxant neurotransmitter nitric oxide was observed.
      These results provide further evidence for the key role played by cholinergic
      nerves in regulating airway smooth muscle tone and bronchial blood flow and
      provide further evidence that acetylcholine is not coreleased with the
      neurotransmitter(s) mediating relaxations of airway smooth muscle.

PMID- 9142949
TI  - Ontogeny of gamma-glutamyltransferase in the rat lung.
AB  - gamma-Glutamyltransferase (gamma-GT) is a key enzyme in the metabolism of
      glutathione and glutathione-substituted molecules. The gamma-GT gene is expressed
      in two epithelial cells of the adult lung, the bronchiolar Clara cell and the
      alveolar type II cell. Because pulmonary glutathione metabolism may be important
      in the perinatal period, we studied gamma-GT ontogeny in the developing rat lung.
      In the late fetal and early postnatal lung, gamma-GT mRNA was below detectable
      limits on Northern blots. Pulmonary gamma-GT protein and enzyme activity were
      present at low levels after fetal day 18. gamma-GT protein appeared as a high
      molecular-mass band (>95 kDa), with small amounts of enzymatically active gamma
      GT heterodimer. Between the 2nd and 3rd postnatal wk, pulmonary gamma-GT mRNA
      expression increased in association with an increase in gamma-GT protein and
      enzyme activity that reached adult lung levels. At this time, gamma-GT protein
      appeared predominantly in the heterodimeric form with small amounts of the >95
      kDa protein. Immunocytochemistry revealed that, in the fetal and early postnatal
      lung, gamma-GT was expressed only in the alveolar type II cell, whereas the Clara
      cell became the major site of gamma-GT mRNA and protein expression by 2-3 wk and
      in the adult. Type II cells isolated from the fetal lung express gamma-GT mRNA
      and synthesize the >95-kDa form of gamma-GT in excess of the heterodimer. These
      studies demonstrate that the alveolar type II cell is the only cell producing
      gamma-GT in the newborn lung and that it synthesizes a form of gamma-GT that
      appears to differ from that produced at a later time point by the Clara cell.

PMID- 9142950
TI  - Glucocorticoid treatment decreases muscarinic receptor expression in canine
      airway smooth muscle.
AB  - Corticosteroids upregulate the beta-adrenergic pathway, but little is known about
      corticosteroid regulation of muscarinic pathways. Basenji-greyhound (BG) dogs
      treated for 3 days with methylprednisolone (MPS) but not deoxycorticosterone
      (DOC) had decreased numbers of muscarinic receptors in airway smooth muscle
      homogenates as determined by radioligand binding with 1-[3H]quinuclidinyl
      benzilate (vehicle control, 578 +/- 53 fmol/mg protein; MPS, 290 +/- 22 fmol/mg
      protein; DOC, 565 +/- 141 fmol/mg protein). Competition radioligand binding with
      the M2-selective antagonist tripitramine showed a decrease in both the M2 and M3
      muscarinic receptors with no changes in receptor affinities (M2: vehicle control,
      478 +/- 41 fmol/mg protein; MPS, 265 +/- 20 fmol/mg protein, M3: vehicle control,
      89 +/- 13 fmol/mg protein; MPS, 25 +/- 16 fmol/mg protein). In vitro treatment of
      airway smooth muscle from control BG dogs with MPS had no effect on muscarinic
      receptor number, despite increased expression of beta-adrenergic receptors. Thus
      glucocorticoids indirectly decrease the expression of M2 and M3 muscarinic
      receptors in airway smooth muscle, which, in part, may account for their
      beneficial effects in the treatment of asthma.

PMID- 9142951
TI  - cAMP and genistein stimulate HCO3- conductance through CFTR in human airway
      epithelia.
AB  - We studied the role of the cystic fibrosis transmembrane conductance regulator
      (CFTR) Cl- channel as an HCO3- conductor during adenosine 3',5'-cyclic
      monophosphate (cAMP)-dependent regulation in human airway epithelial cell lines.
      HCO3- or Cl- currents across the apical membrane were measured in the presence of
      an HCO3- or Cl- gradient under short-circuit conditions in intact and alpha-toxin
      permeabilized monolayers, which allowed manipulation of the intracellular
      regulators cAMP and ATP. CFTR as the current carrier for HCO3- was identified by
      1) stimulation by cAMP, 2) ATP dependence, 3) blocker sensitivity, 4) stimulation
      by genistein, and 5) lack of stimulation in CF epithelia bearing mutated delta
      F508 CFTR. In pulmonary alpha-toxin-permeabilized Calu-3 monolayers, cytosolic
      addition of 100 microM cAMP stimulated apical HCO3- currents from -9.4 +/- 1.6 to
      -31.1 +/- 3.9 microA/cm2 (n = 18), and apical Cl- currents increased from -54.1
      +/- 7.1 to -203.2 +/- 15.4 microA/cm2 (n = 27). Average relative permselectivity
      for HCO3- vs. Cl- was approximately 15%. Absence of cytosolic ATP resulted in
      loss of cAMP stimulation of HCO3- and Cl- currents. Genistein (50 microM), which
      has been proposed to inhibit phosphatases controlling apical CFTR, as well as the
      alkaline phosphatase inhibitor (-)-p-bromotetramisole (1 mM) further activated
      cAMP-stimulated HCO3- and Cl- currents. Activated currents remained stimulated on
      removal of cAMP, suggesting inhibition of a protein phosphatase by genistein and
      bromotetramisole. The Cl- channel blockers glibenclamide (300 microM) and N
      phenylanthranilic acid (5 mM), but not 4,4'-dinitro-2,2'-stilbenedisulfonic acid
      (100 microM), inhibited cAMP- and genistein-stimulated HCO3- and Cl- currents.
      Blocker effects were absent in human CF tracheal cells homozygous for the delta
      F508 mutation of CFTR (CFT1); Cl- and HCO3- currents were rescued in CFT1 cells
      recombinantly expressing wild-type CFTR. Thus CFTR functions as a HCO3- and Cl-
      conductor, and genistein and bromotetramisole maximize CFTR activity in airway
      epithelial cells.

PMID- 9142952
TI  - Differential effects of polycationic protein on Cl- secretory and Na+ absorptive
      airways.
AB  - Effects of cationic proteins on electrolyte transport depend on the specific
      channels and electrochemical driving forces expressed by epithelia. The
      bioelectric responses of canine tracheal and bronchial epithelia (CTE and CBE,
      respectively) to a polycationic protein, protamine, were therefore compared. CTE
      exhibited a brief transient inhibition of shortcircuit current (I(SC)) followed
      by a prolonged increase of 18 microA/cm2. The apical membrane transiently
      hyperpolarized and then depolarized by 11 mV. The increase in I(SC) was inhibited
      by bumetanide. Adenosine 3',5'-cyclic monophosphate, ionomycin, and thapsigargin
      attenuated the response whereas indomethacin or hypotonic solution had no effect,
      indicating that latent cystic fibrosis transmembrane regulator Cl- channels were
      activated. CBE preparations exhibited a 4-microA/cm2 decrease in I(SC), 2 mV
      hyperpolarization of the apical membrane, and an increase in fractional
      resistance of the apical membrane on exposure to protamine. These results were
      consistent with inhibition of the Na+ conductance in the apical membrane of CBE
      and confirmed that polycationic proteins exert differential effects on Cl-
      secretory and Na+ absorptive airways.

PMID- 9142953
TI  - Nuclear magnetic resonance study of lung water compartments in the rat.
AB  - Nuclear magnetic resonance transverse relaxation time (T2) was previously
      measured in studies of lung water. The T2 decay curves for peripheral lung tissue
      were found to be multiexponential with two T2 components: T2 fast (T2f) and T2
      slow (T2s). This behavior was explained by the compartmentalization of water, in
      which the protons of water are restricted and do not undergo rapid exchange
      between the compartments. We investigated the origin of the water for these T2
      components using excised rat lungs. The effect of magnetic field inhomogeneity
      due to air-tissue interfaces was examined by degassing some lungs. The
      contribution of intravascular water was examined by perfusing the lungs with oil
      or NaCl solutions. Degassing produced a greater increase in the T2f than the T2s
      component, indicating that the water in the alveolar walls exposed to air spaces
      contributed to the T2f. Perfusion with oil decreased the T2s, indicating that
      intravascular water contributed to the T2s component. The effects of
      intravascular osmotic pressure on the T2f and T2s components suggest that
      intracellular water is related to the T2f component.

PMID- 9142954
TI  - Involvement of NF-kappaB in silica-induced cyclooxygenase II gene expression in
      rat alveolar macrophages.
AB  - The role of nuclear factor (NF)-kappaB transcription factor in silica-induced
      cyclooxygenase (COX) II gene expression was examined in the rat alveolar
      macrophage cell line NR8383. Our results indicate that NF-kappaB can be activated
      in this cell line by silica exposure. Suppression of NF-kappaB activation in
      these cells leads to an attenuation of COX II mRNA accumulation induced by
      silica. Using an electrophoretic mobility shift assay and a reporter gene assay,
      we provide evidence that at least two kappaB sites in the 5'-flanking region of
      the rat COX II gene are involved for silica-induced transcriptional control of
      the COX II gene. The first motif, -404 GGGGATTCCC -395, is absolutely conserved
      in sequence and is localized in a similar position among the COX II genes found
      in humans, rats, and mice. The second motif, -91 GGGGAAAGCC -82, was conserved
      only in the mouse and rat COX II genes in sequence and in location. Aspirin, a
      COX inhibitor, was shown to suppress silica-induced NF-kappaB activation.
      However, prostaglandin E2, one of the important downstream reaction products
      catalyzed by the COX enzyme, was also shown to attenuate silica-induced NF-kappaB
      activation by retarding the degradation of silica-induced inhibitor NF-kappaB.
      These results suggest that an interdependent regulation may exist between NF
      kappaB activation and COX or its products.

PMID- 9142955
TI  - Effects of charybdotoxin on responses to nitrosovasodilators and hypoxia in the
      rat lung.
AB  - This study investigated the effects of the Ca2+-sensitive K+ channel antagonist
      charybdotoxin on responses to the nitrosovasodilators nitroglycerin and sodium
      nitroprusside and on pulmonary pressor responses to ventilatory hypoxia in the
      isolated blood-perfused rat lung. Injections of nitroglycerin and sodium
      nitroprusside induced dose-related decreases in pulmonary arterial perfusion
      pressure when tone was increased with U-46619, whereas ventilatory hypoxia (3% O2
      5% CO2-balance N2) increased pulmonary arterial perfusion pressure in a
      reproducible manner. After administration of charybdotoxin, the pressor response
      to ventilatory hypoxia was significantly increased, whereas charybdotoxin
      significantly decreased vasodilator responses to nitroglycerin and sodium
      nitroprusside but had no effect on the vasodilator responses to albuterol or to
      isoproterenol when tone was increased with U-46619. The results of the present
      study show that charybdotoxin enhances the pressor response to ventilatory
      hypoxia and significantly decreases responses to nitric oxide-donating
      vasodilator agonists in a selective manner. These data suggest that the response
      to ventilatory hypoxia is modulated by alterations in Ca2+-sensitive K+ channel
      activity and suggest that vasodilator responses to the nitric oxide donors
      nitroglycerin and sodium nitroprusside are dependent on the opening of large
      conductance Ca2+-sensitive K+ channels in the pulmonary vascular bed of the rat.

PMID- 9142956
TI  - On increasing the number of pulmonary alveoli in rats by postnatal treatment with
      retinoic acid.

PMID- 9142957
TI  - Primary systemic treatment with weekly doxorubicin monotherapy in women with
      locally advanced breast cancer; clinical experience and parameters predicting
      outcome.
AB  - Sixty-three patients (median age 64 years) with locally advanced breast cancer
      (T3, T4 and/or N2) were treated with primary 'neoadjuvant' chemotherapy given as
      weekly doxorubicin monotherapy (14 mg/m2 per dose). Seven patients had solitary
      distant metastasis at the time of diagnosis. Twenty-eight patients (45%) achieved
      'partial response' to primary chemotherapy. Twenty-nine patients (46%) had
      'stable disease', and 6 patients (9%) had 'progressive disease' during treatment.
      Following chemotherapy, 52 patients were subjected to surgery and another 4
      patients had surgery performed after radiotherapy. Surgery was considered
      impossible in only three patients. After a median observation time of 23 months,
      local recurrences were observed in 2 patients, one with progressive disease and
      one with stable disease during chemotherapy. Univariate analyses revealed that
      large tumour size, high histological grade and high mitotic frequency were
      associated with poor primary response to chemotherapy. Recent studies have
      demonstrated a correlation between p53-mutations and chemotherapy response.

PMID- 9142958
TI  - Mechanisms of tamoxifen resistance in the treatment of advanced breast cancer.
AB  - Multiple mechanisms may render breast cancer cells resistant to treatment with
      the antiestrogen tamoxifen. This review describes changes in the estrogen
      receptor (ER) signaling pathway which may lead to tamoxifen resistance: change in
      uptake or metabolism of tamoxifen, loss of expression of ER, decreased expression
      of ER, expression of mutant or variant forms of ER, intact ER but loss of
      cofactors, ligand-independent ER activation, modification of the estrogen
      response element, altered post-receptor events. Non-ER related alterations are
      also mentioned.

PMID- 9142959
TI  - Letrozole (CGS 20267), a new oral aromatase inhibitor for the treatment of
      advanced breast cancer in postmenopausal patients.
AB  - Letrozole is a new orally, active, potent, and highly specific non-steroidal
      aromatase inhibitor. Letrozole is about 200 and 10000 times as potent as
      aminoglutethimide (AG) in vitro and in vivo, respectively. Letrozole was tested
      in healthy men and postmenopausal women and in postmenopausal patients with
      advanced breast cancer (ABC). Levels of circulating estrogens decreased by more
      than 75 to 95% from pre-treatment levels have been observed in patients treated
      with daily doses of 0.1 to 5 mg letrozole. No clinically relevant changes in
      other hormones of the endocrine system were found. In four phase Ib/IIa trials,
      letrozole has shown anti-tumor activity in postmenopausal patients with ABC
      previously treated with hormonotherapy and/or chemotherapy. Letrozole was well
      tolerated. Phase IIb/III studies are on going to compare two doses of letrozole
      with megestrol acetate or AG in order to confirm the anti-tumor efficacy of
      letrozole in the treatment of ABC in postmenopausal patients who
      progressed/relapsed following treatment with anti-estrogens.

PMID- 9142960
TI  - Insulin-like growth factors in breast cancer.
AB  - Insulin-like growth factor (IGF)-I is one of the most potent mitogens to many
      breast cancer cell lines in vitro. Effective growth inhibition in vitro may be
      achieved by antibodies to the type I IGF receptor (IGF-IR) or by using antisense
      strategies. Most human breast cancers express IGF-IR in vivo. Thus, different
      therapeutic strategies aimed at inhibiting ligand stimulation of the IGF-IR may
      be an attractive treatment option against breast cancer. Several drugs commonly
      used in breast cancer influence the IGF system both in vitro and in vivo. While
      antioestrogens such as tamoxifen and droloxifene reduce the expression of IGF-IR
      in vitro and suppress plasma levels of IGF-I but elevate IGF-binding protein-1 in
      vivo, megestrol acetate may reduce the delivery of IGFs to the tissues by
      inhibition of IGFBP-3 protease activity.

PMID- 9142961
TI  - The future of bisphosphonates in cancer.
AB  - Bisphosphonates, in conjunction with rehydration, are now the treatment of choice
      for hypercalcaemia of malignancy. They can also relieve bone pain and improve
      quality of life as single agent therapy and, in conjunction with systemic
      anticancer treatments, can prevent skeletal complications and slow down the
      metastatic process. The clinical effects are greatest and most clearly defined in
      breast cancer and multiple myeloma, but, theoretically, clinical benefit should
      be achievable across the entire spectrum of metastatic bone disease. The new
      biochemical markers for measuring bone resorption are for the first time
      providing a direct assessment of the effects of treatment on bone. It is hoped
      that they will enable a more scientific selection of the type, dose and schedule
      of bisphosphonate required for the best compromise between efficacy, convenience
      and patient acceptability. We can expect to see a rapid increase in the use of
      bisphosphonates in malignancy (especially breast cancer and myeloma). Careful
      assessment of the health-care economics of this new treatment modality is
      urgently needed.

PMID- 9142962
TI  - Novel endocrine therapies in breast cancer.
AB  - Endocrine therapy of breast cancer consists of a variety of both medical and
      surgical ablative treatment modalities, but ablative therapy is increasingly
      replaced by medical treatment. Most endocrine therapies have more than one
      endocrine effect, frequently together with direct growth inhibitory actions via
      receptors. Endocrine therapy can be effective in all phases of the disease, but
      curative only in early disease while in advanced cancer it can only prolong
      survival. In the past decade the number of available endocrine agents has been
      drastically increased. Novel approaches in the endocrine therapy of breast cancer
      are application of new antiestrogens, antiprogestins, new potent aromatase
      inhibitors, analogues of luteinizing hormone-releasing hormone (LHRH-A) and
      somatostatin, inhibitors of prolactin secretion, vitamin A and D analogues,
      bisphosphonates, growth factor antagonists, tyrosine protein kinase inhibitors,
      protease inhibitors, inhibitors of angiogenesis, radiolabeled hormones and
      monoclonal antibodies. New cell biological factors such as oncogenes and
      suppressorgenes, secretory proteins and membrane receptors can be used not only
      as prognostic factors but also for prediction of type of response to endocrine
      and chemotherapy. Thus, these cell biological parameters can be used to select
      high and low risk patients, type of systemic treatment, and can also be used as
      targets for new treatment modalities. Future studies on treatment of all stages
      of disease will increasingly focus on promising combined treatment modalities.

PMID- 9142963
TI  - Aromatase inhibition for breast cancer treatment.
AB  - While the first generation aromatase inhibitor aminoglutethimide and second- and
      third generation inhibitors like formestane and fadrozole all have been found to
      inhibit in vivo aromatization by 85-93%, the novel aromatase inhibitors letrozole
      and arimidex inhibit in vivo aromatization by 97-99%. However, we do not know
      whether these drugs cause a higher response rate or a longer duration of
      remission compared with less potent aromatase inhibitors. Lack of cross
      resistance to steroidal and non-steroidal aromatase inhibitors suggests that
      these drugs may have partially different mechanisms of action, probably by
      influencing the intratumour aromatase enzyme. Recent studies have shown that
      breast cancer cells may adapt to alterations in oestrogen concentration in vitro
      by increasing their sensitivity. The observation that patients suffering relapse
      following castration, hypophysectomy or adrenalectomy may respond to treatment
      with aromatase inhibitors suggests that similar mechanisms could be responsible
      for acquired resistance to oestrogen deprivation.

PMID- 9142964
TI  - Proper sequence of endocrine therapies in advanced breast cancer.
AB  - Tamoxifen (TAM) is widely used as therapy in early breast cancer and first-line
      endocrine therapy in metastatic disease. Despite this therapy, many patients
      relapse and an important question is: What is the preferred sequence of endocrine
      therapies in metastatic breast cancer (MBC). While treatment with oophorectomy,
      aminoglutethimide or progestins have been a logical choice after failure to
      Tamoxifen recent research has extended the options for endocrine therapy of MBC.
      New selective aromatase inhibitors (AI) are now in clinical use. The first
      commercially available of these inhibitors is LENTARON. The active ingredient of
      LENTARON is a steroidal compound 4-OH-androstenedione: Formestane. It is
      presented as a depot formulation and applied as an i.m. injection of 250 mg every
      second week. Previous findings from phase II trials have indicated similar
      activity as other endocrine treatment modalities. Clinical investigations in
      properly conducted phase III trials have revealed that the efficacy of LENTARON
      matches the results which can be obtained with TAM and Megace in trials of first
      and second-line endocrine therapy. Fifty-four and 51% of MBC patients,
      respectively, did benefit from therapy with LENTARON in these phase III trials by
      achieving objective responses or stable disease. Moreover, similar overall
      survival was seen. The systemic tolerability of LENTARON is comparable to that of
      TAM, and LENTARON seems less systemically toxic than Megace. Local side effects
      occured in approximately 7% of the patients giving rise mainly to pain or
      inflammation at the injection site. In elderly patients, LENTARON therapy assures
      compliance and no interference with other oral medications has been observed. In
      conclusion, since the endocrine treatment modalities are comparable in terms of
      efficacy the optimal sequence of these treatments is based upon differences in
      tolerability. Patients previously treated with Tamoxifen and with a high
      probability of a further endocrine response could preferably be treated with a
      selective AI like LENTARON as second-line endocrine therapy followed by a
      progestin upon progression in responders.

PMID- 9142965
TI  - Analgesic effect of bisphosphonates on bone pain in breast cancer patients: a
      review article.
AB  - Bisphosphonates exert their analgesic effect by several mechanisms. The long-term
      effects are probably due to osteoclast inhibition. The acute pain-relieving
      effect, which occurs within days or a week, is likely to be associated with the
      reduction of various potentially pain-producing substances. As regards
      pamidronate, several open, controlled studies have shown a significant effect on
      bone pain in 30-70% of breast cancer patients. The effects have been dose
      dependent: a mean dose of 15 mg i.v./week is obviously suboptimal, whereas higher
      doses yield markedly better effects. The dose response is most evident at doses
      between 15 and 30 mg/week. Furthermore, the total dose per infusion is of
      interest: 30 mg every 2 weeks is an ineffective treatment, whereas 60 mg every 4
      weeks is more effective. Thus, both the dose per week and the total dose per
      infusion are of importance in order to achieve optimal treatment. Patients with
      rapid progression of their disease require higher doses than patients with slow
      progression. Parenteral therapy is more effective than oral treatment. Both oral
      and parenteral clodronate exert a significant, positive effect on total skeletal
      morbidity and thus probably also on bone pain. Unfortunately, pain measurements
      have not been performed and evidence for pain reduction is indirect. Specific
      pain studies and studies of quality of life, with few exceptions, are, however,
      still lacking.

PMID- 9142966
TI  - Bisphosphonate therapy in multiple myeloma.
AB  - Lytic bone lesions, pathological fractures, hypercalcaemia and osteoporosis are
      common features in patients with multiple myeloma. Adjunctive therapeutic
      modalities in addition to antimyeloma therapy have been sought to ameliorate
      these clinical consequences of bone disease. Bisphosphonates appear to be useful
      in this respect. In addition to correcting hypercalcaemia, they reduce the amount
      of new bone lesions and pathological fractures in myeloma patients.
      Bisphosphonates also relieve bone pain. In placebo-controlled studies clodronate
      (1600-2400 mg/d orally) and pamidronate (90 mg intravenously once every month)
      have produced clinically significant effects in myeloma patients. Bisphosphonates
      are a useful adjunct therapy in patients with multiple myeloma.

PMID- 9142967
TI  - Concurrent tamoxifen (TAM) + cyclophosphamide, epirubicin, and fluorouracil (CEF)
      versus TAM + delayed CEF after six months of endocrine therapy in metastatic
      breast cancer--a randomized trial from the Danish Breast Cancer Cooperative Group
      (DBCG).

PMID- 9142968
TI  - Palliative treatment of bone metastases.
AB  - Bone metastases are frequently one of the first signs of disseminated disease in
      cancer patients and are especially seen in patients with breast, prostate and
      lung cancer. The prognosis of these patients is generally poor and the treatment
      is primarily palliative: the intention is to relieve pain, prevent fractures,
      maintain activity and, if possible, to prolong survival. Besides analgesics the
      therapeutic options include local treatment with radiotherapy and/or surgery, and
      systemic treatment using chemotherapy, endocrine therapy, radioisotopes as well
      as bisphosphonates. Social and psychological supportive care is also very
      important. Radiotherapy plays an important role, but the other modalities such as
      bisphosphonates may also offer the same level of palliation, but their definite
      role has not been as clearly defined. There have been few randomized trials
      comparing the therapeutic options, and the criteria for assessing response to
      therapy have, in general, been poorly defined. There is a need for rigorous
      clinical investigations which assess the efficacy of the various therapeutic
      possibilities by using well-defined and validated response criteria such as pain
      and quality of life.

PMID- 9142969
TI  - Rationale for the use of bisphosphonates in breast cancer.
AB  - The variability of different breast cancers in the susceptibility to metastatic
      bone disease is poorly understood. Factors that determine the viability of
      metastatic cells are also poorly understood, but may depend in part upon gene
      expression of PTHrP and the vitamin D receptor. In contrast, much more is known
      of the manner in which metastatic breast disease affects bone remodelling to
      induce osteolytic bone disease. Mechanisms include a generalized increase in
      activation frequency at sites close to metastatic tissue, an imbalance between
      the amount of bone formed and that resorbed within resorption cavities, and
      uncoupling of bone formation from bone resorption. The greatest morbidity from
      metastatic bone disease arises from osteolytic disease and gives rise to
      hypercalcaemia, bone pain and fractures. Since osteolysis is primarily mediated
      by the activation of osteoclasts, there has been a great deal of interest in the
      use of agents which primarily affect bone metabolism to alter the natural history
      of metastatic bone disease. Non-steroidal anti-inflammatory agents and cytotoxic
      agents are capable of inducing responses in bone, but are limited by their
      toxicity when effective doses are utilized. The use of calcitonin in the long
      term suppression of osteolysis has also been disappointing. The bisphosphonates
      are, however, capable of inducing sustained decreases in osteoclast activity and
      numbers in patients with osteolytic bone disease. There are now several studies
      which have examined the effects of the bisphosphonates on skeletal morbidity in
      breast cancer. Both clodronate and pamidronate decrease the incidence of
      hypercalcaemia, bone pain and pathological fractures, but do not significantly
      alter mortality. Given, however, the unchanging survival in patients with
      metastatic bone disease, significant improvements in the quality of remaining
      life is an important therapeutic effect.

PMID- 9142970
TI  - Endocrine treatment of advanced breast cancer.
AB  - Endocrine treatment is the preferred first-line therapy for advanced breast
      cancer because of its good tolerability. There are several groups of agents which
      differ in their mode of action but almost all in some way reduce stimulation by
      oestrogen. Over recent years, there has been a substantial increase in the number
      of medical agents in clinical trial. New antioestrogens with reduced or no
      agonist activity, and potent, more specific, aromatase inhibitors are now
      reaching the clinic. In most cases, the clinical effectiveness of these agents
      remains to be fully established and their optimal therapeutic application is yet
      to be determined.

PMID- 9142972
TI  - Second-line endocrine treatment of advanced breast cancer--a randomized cross
      over study of medroxy-progesterone acetate and aminoglutethimide.

PMID- 9142971
TI  - Efficacy of pamidronate in breast cancer with bone metastases: a randomized
      double-blind placebo controlled multicenter study.

PMID- 9142973
TI  - Chemotherapy resistance mechanisms.

PMID- 9142974
TI  - Bisphosphonate therapy in metastatic breast cancer.
AB  - Five long-term controlled studies on the effect of supportive bisphosphonate
      treatment in metastatic breast cancer with bone metastases have been published.
      In two of the studies pamidronate was used and in three clodronate. According to
      these trials supportive bisphosphonate treatment in metastatic breast cancer
      diminishes the risk of malignant, pathological fractures and bone pain. In
      several of these trials a retarding effect on the progression of previous and new
      bone metastases could also be documented. One further large trial, hitherto
      published only in abstract form, indicates that the development of bone invasion
      can also be retarded by bisphosphonate treatment in patients with metastatic
      breast cancer without bone metastases.

PMID- 9142975
TI  - Predictive factors for response to cytotoxic treatment in advanced breast cancer:
      a review.

PMID- 9142976
TI  - Endocrine resistance in advanced breast cancer.
AB  - Although about half of patients with advanced breast cancer show either an
      objective response or disease stabilization on first line endocrine therapy,
      virtually all eventually relapse. Few of those patients that fail to respond to
      first-line treatment, respond to challenge with a second agent. In most cases,
      the cause of this de novo resistance appears to be the presence of only very low
      levels of oestrogen receptor (ER) and presumed growth dependence on other
      pathways. Patients who develop acquired resistance after an initial response,
      have approximately a 50% chance of responding to a further agent. The most
      frequently used first-line agent is tamoxifen, and the understanding of acquired
      endocrine resistance mainly relates to this agent. Selection of ER-ve clones of
      cells does not appear to occur frequently, and there is little clinical evidence
      to support the role of ER variants or mutants. There is evidence, however, that
      in some patients the intratumoural concentration of tamoxifen is substantially
      reduced at relapse, despite no change in plasma levels.

PMID- 9142977
TI  - Overview on human breast cancer with focus on prognostic and predictive factors
      with special attention on the tumour suppressor gene p53.
AB  - A long list of potential prognostic markers has been analysed for breast cancer,
      some of them will be reviewed in this article. The lymph node status is still the
      best prognostic marker. The lymph node status combined with information on tumour
      size, receptor- and proliferation status of the tumour should be analysed as
      standard for all breast cancer patients. Prognostic information for breast cancer
      patients has also been described for the membrane protein c-erbB2, the protease
      cathepsin D, plasminogen activators and inhibitors, certain oncogenes and tumour
      suppressor genes. Some of these factors also give potential additional
      information on the response to different oncological therapies, and are better
      denoted predictive factors. In this overview we shortly describe the above
      mentioned prognostic factors with major focus on the tumour suppressor gene p53
      and its prognostic value and potential predictive value.

PMID- 9142978
TI  - Spatial regulation of neuronal gene expression in response to nerve growth
      factor.
AB  - To examine the cellular mechanisms whereby distally derived growth factors
      regulate nuclear responses in neurons, we have utilized compartmented cultures of
      sympathetic neurons to examine the regulation of two nerve growth factor (NGF)
      inducible genes, tyrosine hydroxylase (TH) and p75 neurotrophin receptor
      (p75NTR). These studies demonstrate that NGF can signal retrogradely to mediate
      the induction of TH and p75NTR mRNAs. However, quantitative differences occurred
      as a function of the spatial localization of NGF exposure; application of NGF to
      cell bodies and proximal axons elicited peak levels of neuronal gene expression
      that were two- to threefold higher than when NGF was applied to distal axons
      alone. Furthermore, neurons responding maximally to NGF on distal axons were
      still able to respond to NGF administered to cell bodies and proximal axons.
      Biochemical analysis indicated that this difference in responsiveness was not due
      to differences in the number of TrkA/NGF receptors in the two compartments. Thus,
      although NGF signals retrogradely to mediate nuclear responses, the magnitude of
      these responses differs as a function of the spatial location of the activated
      NGF receptor:ligand complex. Moreover, these data suggest that neurons may be
      able to respond to a second cellular source of neurotrophins, even when target
      derived neurotrophins are not limiting.

PMID- 9142979
TI  - Surface localization of the sea urchin egg receptor for sperm.
AB  - The sea urchin egg receptor for sperm is thought to be involved in species
      specific sperm-egg interactions at the egg surface. Recent revisions in the
      deduced amino acid sequence of the cloned cDNAs indicate that the protein encoded
      does not possess the common structural hallmarks of a membrane protein. Thus,
      investigation of the localization and association of the protein with the egg
      surface is crucial. We describe and characterize a new monoclonal antibody raised
      against recombinant sperm receptor protein. This antibody, in conjunction with
      several polyclonal antibodies, was used to study the receptor protein in eggs.
      Immunoprecipitation studies indicated that the antibodies recognize the high Mr
      (ca. 350 K) sperm receptor protein which copurified with egg plasma membrane
      vitelline layer complexes. The sperm receptor protein was solubilized only by
      detergents and not by treatments designed to solubilize peripherally associated
      or lipid-anchored membrane proteins, suggesting a tight association with the
      membrane fraction. Confocal immunofluorescence microscopy of live eggs indicated
      surface staining. Finally, lysylendoproteinase C treatment of live eggs resulted
      in a loss of the high Mr receptor protein epitopes, and the concomitant release
      of a 70-kDa proteolytic fragment, which correlated with a reduced ability of the
      eggs to be fertilized. Taken together, these data indicate that at least some
      fraction of the sperm receptor protein is present on the egg surface, a requisite
      locale for a sperm binding protein.

PMID- 9142980
TI  - Reexamination of the sequence of the sea urchin egg receptor for sperm:
      implications with respect to its properties.
AB  - A reexamination of the cDNA clones of the Strongylocentrotus purpuratus sea
      urchin egg receptor for sperm resulted in several important changes to the
      sequence. By using both rapid amplification of cDNA ends (RACE) and Northern blot
      analysis for confirmation, the corrected deduced amino acid sequence was shown to
      lack a classical signal peptide. In addition, a frame shift resulted in a stop
      codon terminating the deduced sequence prior to a putative transmembrane domain,
      thereby truncating the protein to 889 amino acids. The deduced amino acid
      sequence of the receptor has high sequence similarity to the hsp 110 subfamily of
      proteins. These findings on the primary structure of the egg receptor for sperm
      raise important questions concerning the mechanism by which the heavily
      glycosylated receptor is localized to the extracellular surface of the egg and to
      the cortical granules.

PMID- 9142981
TI  - Identification of a 97-kDa heat shock protein from S. franciscanus ovaries with
      94% amino acid identity to the S. purpuratus egg surface receptor for sperm.
AB  - To identify species-specific regions of the sea urchin egg surface receptor for
      sperm, we cloned and sequenced the cDNA from S. franciscanus (Sf) ovary mRNA that
      is homologous to the S. purpuratus (Sp) sperm receptor sequence. The Sf cDNA
      contains an 886-amino-acid open reading frame (ORF) that is 96% identical at the
      nucleotide level to the Sp sperm receptor sequence over 2.9 kb. In contrast to
      the published Sp sequence, the Sf sequence does not encode a signal peptide or
      transmembrane domain. However, like the Sp sperm receptor sequence, the Sf
      protein has substantial similarity to the 70-kDa heat shock family of proteins
      and appears to encode a member of a newly identified subfamily of hsp70-related
      proteins designated hsp110/SSE. A BLAST search using the 5' end of the published
      Sp cDNA sequence as a query indicates that a segment of approximately 400 bp,
      which encodes the putative signal sequence, is 95% identical to Sp mitochondrial
      DNA. Resequencing of the Sp cDNA clone failed to confirm the presence of the
      published transmembrane and cytoplasmic domains. These results suggest that the
      published sequence of the Sp egg receptor for sperm may contain errors in the
      critical regions that were believed to encode an amino-terminal signal sequence,
      transmembrane domain, and cytoplasmic tail and that the protein products encoded
      by these cDNAs are highly related to mammalian cytoplasmic hsp110s.

PMID- 9142982
TI  - Expression of heparan sulfate proteoglycan (perlecan) in the mouse blastocyst is
      regulated during normal and delayed implantation.
AB  - Previous studies have shown that expression of the heparan sulfate proteoglycan,
      perlecan, on the external trophectodermal cell surfaces of mouse blastocysts
      increases during acquisition of attachment competence. However, it is not clear
      if this change in perlecan protein expression also is reflected at the level of
      perlecan mRNA expression. In the present investigation, the spatial and temporal
      patterns of perlecan mRNA expression in the mouse embryo during the
      periimplantation period were examined by in situ hybridization and reverse
      transcriptase-polymerase chain reaction. In addition, a delayed implantation
      model was used to determine the expression of perlecan mRNA and protein in
      dormant and estrogen-activated hatched blastocysts. The results demonstrate that
      perlecan mRNA expression is low in morulae, but increases in Day 4 blastocysts,
      attaining maximal expression in Day 4.5 attachment-competent blastocysts. In
      contrast, perlecan mRNA is detected in both the dormant and estrogen-activated
      delayed blastocysts; however, within 12 hr of blastocyst activation by estrogen,
      both perlecan protein and heparan sulfate chain expression markedly increase.
      Taken together, these results suggest that during normal development perlecan
      mRNA expression increases with the acquisition of attachment competence.
      Moreover, perlecan protein expression also is attenuated during delayed
      implantation and appears to increase in response to nidatory estrogen, perhaps
      via the increased translation of preexisting perlecan mRNA.

PMID- 9142983
TI  - Neural activity affects distribution of glutamate receptors during neuromuscular
      junction formation in Drosophila embryos.
AB  - Changes in the distribution and density of transmitter receptors in the
      postsynaptic cell are required steps for functional synapse formation. We raised
      antibodies against Drosophila glutamate receptors (DGluR-II) and visualized the
      distribution of receptors during neuromuscular junction formation in embryos. In
      wild-type embryos, embryonic development is complete within 22 hr after egg lying
      (AEL) and neuromuscular junction (NMJ) formation begins at 13 hr AEL. At the time
      of initial synapse formation, DGluR-IIs appeared as clusters closely associated
      with some muscle nuclei. Subsequently, these nonjunctional clusters dispersed
      while DGluR-IIs accumulated at the junctional region. In a paralytic temperature
      sensitive mutant, para(ts1), neural activity decreases drastically at restrictive
      temperatures. When neural activity was blocked throughout synaptogenesis by
      rearing embryos at a restrictive temperature prior to the beginning of
      synaptogenesis, 12 hr AEL, the dispersal of extrajunctional clusters was
      significantly suppressed and no accumulation of receptors at the junction was
      observed at 22 hr AEL. However, when neural activity was blocked later, by
      rearing embryos at a restrictive temperature from 13 hr AEL, DGluR-IIs did not
      accumulate at the NMJ, although extrajunctional clusters dispersed normally.
      These findings suggest that the neural activity differentially regulates
      dissipation of receptor clusters in the nonjunctional region and accumulation of
      receptors at the junctional region.

PMID- 9142984
TI  - Autocrine regulation of neural crest cell development by steel factor.
AB  - Steel factor (SLF) and its cognate receptor, c-kit, have been implicated in the
      generation of melanocytes from migrating neural crest (NC) cells during early
      vertebrate embryogenesis. However, the source of SLF in the early avian embryo
      and its precise role in melanogenesis are unclear. We report here that NC cells
      themselves express and release SLF protein, which in turn acts as an autocrine
      factor to induce melanogenesis in nearby NC cells. These results indicate that NC
      cell subpopulations play an active role in the determination of their cell fate
      and suggest a different developmental role for the embryonic microenvironment
      than what has been previously proposed.

PMID- 9142985
TI  - Pattern formation in janus-mutant zebrafish embryos.
AB  - Mechanisms that underlie the formation of the vertebrate body appear to be highly
      conserved between amphibia and teleosts. For teleosts, however, mesoderm
      induction and the establishment of dorsoventral polarity are poorly understood.
      In this study, we present an analysis of early pattern formation in the zebrafish
      maternal-effect mutation janus. This mutation frequently results in a separation
      of the cleavage stage blastoderm into two halves that undergo separate
      development until fusion occurs at the end of gastrulation. Here, we employ janus
      mutant embryos to analyze the mechanisms of mesoderm formation and ventral
      specification in a teleost. Analysis of the expression of the panmesodermal
      marker no tail in janus-mutant embryos indicates that mesoderm induction depends
      on a marginal position. In an analysis of ventral specification, we show that the
      early expression of the ventral marker GATA-2 is confined to the area on both
      blastodermal halves opposite the dorsal shield region. Since, in janus-mutant
      embryos, the dorsal position is random with respect to the division plane
      bisecting the two blastodermal halves, a variety of dorsoventral asymmetries
      arise within individual embryos. In one constellation, the dorsal position is
      localized to the plane of bisection and two ventral positions develop at opposite
      ends of the blastodermal halves. Hence, ventral fates can be specified at any
      position around the blastodermal margins and are excluded from the dorsal
      position. The diblastodermic system of the janus-mutant embryo allows for the
      study of the interactions of dorsal and ventral determinants in varying spatial
      arrangements. We have studied pattern formation in dorsal half-blastoderms that
      contain the entire shield region but only a reduced ventrolateral marginal zone.
      As assessed by the presence of the most ventral cell type, blood, ventral
      specification within a dorsal half-blastoderm is not suppressed.

PMID- 9142986
TI  - The function of silberblick in the positioning of the eye anlage in the zebrafish
      embryo.
AB  - In zebrafish, as in other vertebrates, an initially singular eye field within the
      neural plate has to split during morphogenesis to allow the development of two
      separated eyes. It has been suggested that anterior progression of midline tissue
      within the neural plate is involved in the bilateralization of the eye field.
      Mutations in the recently identified silberblick (slb) gene cause an incomplete
      separation of the eyes. During gastrulation and early somitogenesis, the ventral
      midline of the central nervous system (CNS) together with the underlying axial
      mesendoderm is shortened and broadened in slb embryos. While in wild-type embryos
      the ventral CNS midline extends to the anterior limit of the neural plate at the
      end of gastrulation, there is a gap between the anterior tip of the ventral CNS
      midline and the anterior edge of the neural plate in slb. To investigate the
      cause for the shortening of the ventral CNS midline in slb we determined the fate
      of labeled ventral CNS midline cells in wild-type and slb embryos at different
      stages of development. In slb, anterior migration of ventral CNS midline cells is
      impaired, which indicates that migration of these cells is needed for elongation
      of the ventral CNS midline. The anterior shortening of the ventral CNS midline in
      slb leads to medial instead of bilateral induction of optic stalks followed by a
      partial fusion of the eyes at later developmental stages. The analysis of the slb
      phenotype indicates that anterior migration of midline cells within the neural
      plate is required for proper induction and subsequent bilateralization of an
      initially singular eye field. These findings may therefore provide a starting
      point in elucidating the role of neural plate morphogenesis in positioning of the
      eyes.

PMID- 9142987
TI  - The organization and animal-vegetal asymmetry of cytokeratin filaments in stage
      VI Xenopus oocytes is dependent upon F-actin and microtubules.
AB  - Confocal immunofluorescence microscopy with anti-cytokeratin antibodies revealed
      a continuous and polarized network of cytokeratin (CK) filaments in the cortex of
      stage VI Xenopus oocytes. In the animal cortex, CK filaments formed a dense
      meshwork that both was thicker and exhibited a finer mesh than the network of CK
      filaments previously observed in the vegetal cortex (Klymkowsky et al., 1987). CK
      filaments first appeared in association with germinal vesicle (GV) and
      mitochondrial mass (MM) of oocytes in early mid stage I, indicating that CK
      filaments are the last of the three cytoskeletal networks to be assembled. By
      late stage I, CK filaments formed complex networks surrounding the GV,
      surrounding and penetrating the MM, and linking these networks to a meshwork of
      CK filaments in the oocyte cortex. During stage III-early IV, CK filaments formed
      a highly interconnected, apparently unpolarized, radial array linking the
      perinuclear and cortical CK filament networks. Polarization of the CK filament
      network was observed during mid stage IV-stage V, as first the animal, then the
      vegetal CK filament networks adopted the organization characteristic of stage VI
      oocytes. Treatment of stage VI oocytes with cytochalasin B disrupted the
      organization of both cortical and cytoplasmic CK filaments, releasing CK
      filaments from the oocyte cortex and inducing formation of numerous cytoplasmic
      CK filament aggregates. CB also disrupted the organization of cytoplasmic
      microtubules (MTs) in stage VI oocytes. Disassembly of oocyte MTs with nocodazole
      resulted in loss of the characteristic A-V polarity of the cortical CK filament
      network. In contrast, disruption of cytoplasmic CK filaments by microinjection of
      anti-CK antibodies had no apparent effect on cytoplasmic or MT organization. We
      propose a model in which the organization and polarization of the cortical
      network of CK filaments in stage VI Xenopus oocytes are dependent upon a
      hierarchy of interactions with actin filaments and microtubules.

PMID- 9142988
TI  - Mouse vaginal opening is an apoptosis-dependent process which can be prevented by
      the overexpression of Bcl2.
AB  - In the mouse, opening of the vaginal cavity to the skin is a late event,
      occurring around the fifth week of life; it can be induced in sexually immature
      mice by beta-estradiol injections. We have generated two lines of transgenic mice
      expressing the human Bcl2 protein in a variety of tissues. The vaginal cavity of
      the transgenic females remained permanently closed, a condition completely
      resistant to beta-estradiol injections; this was accompanied by a considerable
      distension of the genital tract. Histologic studies of vaginal sections at the
      time of opening to the skin in normal mice showed, by the TUNEL method which
      detects nuclei with fragmented DNA characteristic of apoptosis, that this event
      coincides with extensive apoptosis in the lower part of the vaginal mucosa, a
      process prevented in the bcl2 transgenic mice, which express Bcl2 in suprabasal
      epithelial cells and in subepithelial cells of the vaginal mucosa. In contrast,
      two lines of mice bearing a Bcl2 transgene placed under the control of a K10
      keratin promoter, whose expression is restricted to the suprabasal layers of the
      epidermis, had a normal phenotype. Eyelids' formation and opening of the external
      ear canals, which also occur after birth in the mouse, were not altered in any of
      these transgenic lines; histological study of eye and ear sections at the time of
      these events failed to detect apoptosis. In conclusion, the tissue remodeling
      required to complete maturation of the mouse female genital tract at the time of
      puberty is an hormonally triggered apoptosis-dependent process.

PMID- 9142989
TI  - Stepwise requirement of c-kit tyrosine kinase in mouse ovarian follicle
      development.
AB  - Ovarian follicle development is controlled by the cycling variation of
      gonadotrophins derived from the central nervous system. Intragonadal signals are
      also required, especially in the autonomous development of small follicles.
      Receptor tyrosine kinase c-kit and its ligand SLF (Steel factor) are expressed on
      the surface of specific populations of follicle-forming cells in a contiguous
      manner and are thought to have important roles in follicular development. We
      blocked the interaction of c-kit and its ligand by administering the function
      blocking antibody ACK2 to developing mice at various times after birth and
      monitored ovarian follicle development. A blockade of c-kit function disturbed
      the onset of primordial follicle development, primary follicle growth, follicular
      fluid formation of preantral follicles, and penultimate-stage ovarian follicle
      maturation before ovulation. Ovarian follicle growth was dependent on c-kit
      during the first 5 days after birth when the functional FSH receptor is not yet
      expressed in mouse ovary. In contrast, primordial follicle formation and
      survival, small preantral or antral follicle development, ovulation, and
      luteinization of the ovulated follicle were not affected by this antibody. These
      findings indicate the stepwise requirement of c-kit and its ligand interaction
      system in the developing ovarian follicle and that c-kit with its ligand supports
      the autonomous development of ovarian follicle independent of gonadotrophins.

PMID- 9142990
TI  - Developmental testis-specific regulation of mRNA levels and mRNA translational
      efficiencies for TATA-binding protein mRNA isoforms.
AB  - Early spermatids contain roughly 1000-fold more TATA-binding protein (TBP) mRNA
      than do somatic cells. The appearance of TBP-overexpressing spermatids in the
      developing testis is accompanied by a large increase in whole-organ levels of
      total RNA and of poly(A)+ RNA per cell. Whereas somatic cells initiate
      transcription of TBP mRNA at a single promoter/first exon (exon 1C), in adult
      testis, two additional major promoter/first exons (1D and 1E) are used. We have
      examined the expression of the somatic and testis-specific TBP mRNA isoforms
      during rodent testis development. In juvenile testes TBP mRNAs containing either
      exon 1C or exon 1D, but none containing exon 1E, are detected. At 21 days of age,
      all TBP mRNA isoforms begin to overaccumulate. The onset of TBP mRNA
      overaccumulation is marked first by an increase in levels of polysomal TBP mRNA,
      and later by accumulation of mRNP-associated TBP mRNA. In adult testes, only 30%
      of the total TBP mRNA is engaged by polysomes; the remainder is sequestered as
      mRNP particles. All of the TBP mRNA isoforms in adults exist both as free mRNP
      particles and as polysomes; however, the fraction in polysomes varies from 60%
      (exon 1C) to 10% (exon 1E). This suggests that sequences within the first exons
      alter the probability that the mRNA will either assemble into polysomes or into
      translationally inactive mRNP particles.

PMID- 9142991
TI  - C. elegans cell migration gene mig-10 shares similarities with a family of SH2
      domain proteins and acts cell nonautonomously in excretory canal development.
AB  - The mig-10 gene of Caenorhabditis elegans is required for the long-range
      anteroposterior migration of embryonic neurons CAN, ALM, and HSN and proper
      development of the excretory canals. Here, we report the cloning and initial
      molecular characterization of mig-10. The predicted MIG-10 proteins share a large
      region of similarity with a recently identified family of mammalian SH2 domain
      proteins, Grb7 and Grb10. We call this region of similarity the GM region (for
      Grb and Mig). MIG-10 proteins do not contain an SH2 domain, but share with the
      Grbs a pleckstrin homology (PH) domain and proline-rich regions, features
      commonly found in signal transduction proteins. The functions of Grb7 and Grb10
      are unknown, but Grb7 is overexpressed in certain breast cancers, where it is
      bound to the growth factor receptor HER2, while Grb10 has been implicated in
      insulin signaling. We also report the isolation of a new mig-10(e2527) allele, as
      well as the molecular characterization of e2527 (splice acceptor mutation) and
      the canonical ct41 (amber) allele. Finally, we report the results of a genetic
      mosaic analysis which reveal that mig-10 acts cell nonautonomously in the
      development of the excretory canals and suggest a possible focus for mig-10
      activity within descendants of the AB cell lineage. Elucidation of the role of
      mig-10 in C. elegans development should lead to a better understanding of cell
      migration and may shed light on the function of a family of SH2 domain proteins
      apparently involved in signal transduction and cancer.

PMID- 9142992
TI  - Stage-specific signals in germ line differentiation: control of Sertoli cell
      phagocytic activity by spermatogenic cells.
AB  - Differentiation of male germ cells requires a continuous cross-talk with their
      somatic support, the Sertoli cell. An in vitro model of Sertoli cells was
      recently provided by established cell lines which maintain Sertoli-specific
      characteristics, among which is a regulated phagocytic capacity. In vivo, Sertoli
      cells take up the residual cytoplasm expelled from the maturing sperm, a process
      restricted to a limited period of germinal maturation, and they also eliminate
      abnormally differentiated germ cells in case of hormonal deficiency. Cells of the
      Sertoli line efficiently take up latex beads, as well as dead cells in the
      cultures. A semiquantitative assay of phagocytosis was developed, based on the
      uptake of fluorescent latex beads. 15P-1 cultures were found to contain a minor
      fraction of active phagocytes. After addition of a defined fraction of germ
      cells, however, all the cells internalized beads as efficiently as macrophages.
      The inducing cell was identified as the pachytene spermatocyte, a cell type
      which, in vivo, is associated with Sertoli cells when they express their
      phagocytic potential. These inducing meiotic cells were not internalized
      themselves. Rather, they interacted with Sertoli cells via a surface signal that
      was resistant to formaldehyde fixation. The whole induction process does not
      involve changes in Sertoli gene expression, since it occurs even in the presence
      of high doses of cycloheximide. After the required initial contact, further
      maintenance of the activity was dependent on factor(s) secreted in the medium of
      the activated culture. Phagocytosis was, on the other hand, abrogated in the
      presence of factor(s) secreted by a distinct fraction of germ cells, enriched in
      the late stages (second division) of meiosis.

PMID- 9142993
TI  - Retinoic acid disturbs mouse middle ear development in a stage-dependent fashion.
AB  - The mammalian middle ear contains a chain of three ossicles, the malleus, incus,
      and stapes, that transmit into the inner ear the vibrations produced in the
      tympanic membrane by aerial sound. I show here that retinoic acid interferes with
      the formation of the middle ear in a stage-specific fashion. The malformations
      produced are derived from a retinoic acid-induced inhibition of the formation
      and/or migration of the cranial neural crest that generates the middle ear
      skeletal elements and not from a respecification of neural crest identity to more
      posterior fates. I have used these effects of retinoic acid to analyze the
      temporal sequence of events involved in the morphogenesis of the middle ear. I
      show that the middle ear bones develop from several primordia that originate in a
      typical temporal sequence from Day 8 plus 4.5 hr to Day 8 plus 7.5 hr of
      pregnancy. Moreover, interactions between adjacent bones are not required for
      their proper formation. My results also suggest a Hoxa-2-mediated patterning of
      the otic capsule in the region where the oval window is located.

PMID- 9142994
TI  - Differential distribution of a potassium current in immunocytochemically
      identified supraoptic magnocellular neurones of the rat.
AB  - Magnocellular hypothalamo-neurohypophysial neurones display characteristic firing
      patterns, related to the hormone they release. To identify the membrane currents
      that may underlie these firing patterns, we performed whole-cell recording of
      freshly dissociated magnocellular neurones from the supraoptic nucleus. After
      recording, cells were immunocytochemically identified by using highly selective
      monoclonal antibodies raised respectively against vasopressin (AVP) and oxytocin
      (OT) neurophysin. In 64 out of 131 neurones (48.8%), we detected the presence of
      a transient potassium current whose kinetic properties were characteristic of an
      A-current. The A-current was activated by depolarisation over -40 mV, and
      inactivated rapidly with a monoexponential decay (tau = 28 +/- 2.7 ms; n = 33 at
      0 mV). Using conditioning prepulses of 50 ms, the voltage dependence of the
      inactivation was determined, and the data were adequately fit with a Boltzman
      equation (half-maximal inactivation: -42.5 mV). The steady-state time-dependent
      inactivation curve was determined using a prepulse potential at -40 mV, and data
      were best described with a mono-exponential equation (tau = 89.7 ms). The
      sensitivity to 1 mM 4-amino-pyridine (63 +/- 9% inhibition, n = 6), and a
      reversal potential close to the theoretical Nernst equilibrium for potassium (
      56.3 +/- 1 mV, n = 6, vs. -58 mV) confirmed that the transient current studied
      was indeed an A-type potassium current. Immunocytochemical identification
      revealed that the A-current was selectively expressed in OT-neurophysin-positive
      cells. As previous work in hypothalamic slice preparations suggests that the A
      current is expressed by both AVP cells and OT cells, the present data suggest
      that whereas the A-current is expressed in the soma of OT cells, it may be
      expressed only on the dendritic tree of AVP cells, which is truncated in the
      dispersed cell preparation used here. This distribution may play a role in the
      specific firing characteristics of magnocellular neurones.

PMID- 9142996
TI  - Differential effects of three acute stressors on the serotonin 5-HT1A receptor
      system in rat brain.
AB  - The effects of different acute stressors on circulating corticosterone levels, 5
      HT1A receptors and 5-HT1A mRNA levels were measured in male Sprague-Dawley rats.
      Two hours restraint stress, short swim stress (15 min) and long swim stress (30
      min) increased circulating corticosterone levels 10-, 13- and 18-fold,
      respectively, when measured immediately after termination of the stress. Each
      stressor produced a unique profile of changes in 5-HT1A receptors measured in
      coronal sections 24 h after the termination of stress with the antagonist [125I]
      4-(2'-methoxyphenyl)-1-[2'-(n-2"-pyridinyl)-p-iodobenzamido ] ethylpiperazine and
      the agonist [3H]-8-hydroxy-2-(di-n-propylamino)tetralin. Restraint stress
      produced decreases in antagonist binding in the CA3 region and dentate gyrus:
      agonist binding was decreased only in the dentate gyrus. Despite the larger
      elevation in circulating corticosterone level measured after short swim stress,
      no changes in agonist or antagonist binding were detected after this stressor. In
      contrast, the long swim stress increased antagonist binding in the CA2 region and
      in layers IV-VI of the cortex: agonist binding was also increased in all regions
      of the hippocampus and in layers I-VI of the cortex. Thus, restraint and long
      swim stress produce opposite effects on 5-HT1A receptor expression in different
      subregions of the hippocampus. Analysis of presynaptic 5-HT1A receptors in the
      raphe nuclei revealed an increase in antagonist binding in the dorsal raphe
      following long swim stress. No change in the level of 5-HT1A mRNA measured in
      adjacent sections was detected following any of the stressors. The role of
      corticosteroid receptors in these stress-induced alterations of 5-HT1A receptors
      and the potential significance of these alterations in the context of affective
      disorders are discussed.

PMID- 9142995
TI  - Baroreceptor input regulates osmotic control of central vasopressin secretion.
AB  - Sinoaortic baroreceptor denervation (SAD) results in increased osmotically
      induced secretion of vasopressin (VP) and oxytocin (OT) and increased
      cardiovascular responses to many centrally acting pressor agents. Studies were
      conducted to determine whether SAD increases the cardiovascular and endocrine
      responses to direct and peripheral osmotic stimulation of the supraoptic nucleus
      (SON). SON microdialysis was performed in urethane-anesthetized male rats with
      measurement of dialysate peptides, mean arterial pressure (MAP) and heart rate.
      Experiment 1 tested the effect of direct stimulation of the SON with hypertonic
      NaCl in SAD, sham-operated (control) and intake-matched (matched) rats.
      Osmotically induced VP release into the SON was significantly greater in SAD than
      in control or matched groups. VP release peaked at 36 +/- 13 and 15 +/- 7 pg in
      SAD and controls, respectively, with no increase observed in the matched group.
      Plasma VP was significantly elevated after SON osmotic stimulation with no
      differences observed among the groups. The pressor response to osmotic
      stimulation was greater in SAD (29 +/- 4 mm Hg) than in control (20 +/- 3 mm Hg)
      and matched animals (15 +/- 3 mm Hg). Experiment 2 tested the effect of
      intraperitoneal injection of hypertonic NaCl on SON VP and OT release. SAD rats
      showed an increased central VP response to peripheral osmotic stimulation, a 64
      fold increase in SAD as compared to a 4-fold one in controls. Central OT release
      was not significantly altered (peak of 22 +/- 6 vs. 11 +/- 4 pg, SAD vs.
      control). A direct SON osmotic challenge given 3.5 h after the intraperitoneal
      test confirmed an increased VP responsiveness in the SAD group. Plasma VP and OT
      were significantly increased after intraperitoneal hypertonic saline with no
      difference observed between groups. The MAP response to intraperitoneal
      hypertonic saline was greater in the SAD group with an elevation of 37 +/- 4
      versus 18 +/- 3 mm Hg observed in SAD versus control subjects. These results
      demonstrate that baroreceptor denervation produces a state of heightened osmotic
      sensitivity for VP neurons, with evidence for increased central VP release to
      both direct and peripheral hypertonic NaCl stimulation.

PMID- 9142997
TI  - Effect of naltrexone on feeding, neuropeptide Y and uncoupling protein gene
      expression during lactation.
AB  - Neuropeptide Y increases feeding and decreases measures of brown adipose tissue
      thermogenesis. In lactating rats, increased feeding, increased hypothalamic
      neuropeptide Y neuroactivity and decreased thermogenesis occur. Naltrexone is an
      opioid receptor antagonist which decreases neuropeptide Y-induced feeding and
      reverse neuropeptide Y-induced decreases in brown adipose tissue thermogenesis.
      We hypothesized that opioid receptors are involved in neuropeptide Y
      neuroactivity during lactation. To see if naltrexone would alter feeding
      neuropeptide Y gene expression in the arcuate nucleus, neuropeptide Y levels in
      the paraventricular nucleus, and uncoupling protein gene expression in brown
      adipose tissue of lactating rats, osmotic minipumps pre-filled with either 0.9%
      saline or naltrexone (70 micrograms/h) were implanted subcutaneously in 47 female
      Sprague-Dawley rats weighing 309 +/- 5 g. Half these rats were studied on days 10
      16 of lactation, and the other half were studied 7 days after lactation. After 48
      h, neuropeptide Y mRNA levels and uncoupling protein mRNA levels were determined
      using specific cDNA probes. Neuropeptide Y peptide levels in the paraventricular
      nucleus were measured by radioimmunoassay. Naltrexone decreased food intake by
      26% in the postlactating rats, but had no effect on feeding in the lactating
      animals. Lactation resulted in significantly increased arcuate neuropeptide Y
      mRNA, decreased neuropeptide Y levels in the paraventricular nucleus and
      decreased brown adipose tissue uncoupling protein mRNA levels. Naltrexone did not
      influence any of these parameters. Thus, the alterations in neuropeptide Y
      neuroactivity and brown fat thermogenesis which occur in lactation is not altered
      by generalized opioid receptor blockade.

PMID- 9142998
TI  - Hypothalamic galanin gene expression and peptide levels in relation to
      circulating insulin: possible role in energy balance.
AB  - The peptide galanin (GAL) exists in dense concentrations within the medial
      hypothalamus and is synthesized in a population of neurons within the
      paraventricular nucleus (PVN). This peptide has been linked to energy homeostasis
      through its behavioral, metabolic and endocrine actions, including pancreatic
      insulin secretion. This investigation examined whether circulating insulin, in
      turn, has impact on hypothalamic GAL production, GAL mRNA and peptide
      concentrations in the hypothalamus. Streptozotocin (STZ)-induced diabetic rats,
      compared to control subjects, were tested with or without insulin replacement.
      After STZ treatment, the rats exhibited hyperglycemia, increased food and water
      intake, and decreased weight gain compared to controls. These changes were
      reversed by daily, subcutaneous injections of insulin. Measurements of GAL mRNA,
      via solution hybridization/nuclease protection assay, revealed a 6-fold elevation
      after STZ treatment compared to controls, accompanied by a similar rise in GAL
      peptide levels. This increase in GAL message and peptide was reversible by
      insulin and was detected in a mediodorsal hypothalamic (MDH) dissection which
      contains the PVN. It was not seen in a dissection of the mediobasal hypothalamus
      that includes the GAL-synthesizing neurons of the arcuate nucleus. Measurements
      of GAL in discrete hypothalamic nuclei of STZ diabetic rats showed a 100%
      increase in peptide concentrations (p < 0.05) in the PVN that was insulin
      responsive. Other hypothalamic areas examined failed to exhibit any change in
      peptide. These findings are consistent with other evidence indicating an inverse
      association, between circulating insulin and GAL message or peptide in the PVN,
      that may have physiological relevance in the control of energy balance.

PMID- 9142999
TI  - Inhibitory effect of melatonin on gonadotropin-releasing hormone-induced Ca2+
      oscillations in pituitary cells of newborn rats.
AB  - The effect of melatonin on the gonadotropin-releasing-hormone (GnRH)-induced
      oscillatory rises in intracellular calcium concentration, [Ca2+]i, was studied in
      cultured cells from the anterior pituitary gland of 6- to 8-day-old rats. GnRH
      induced [Ca2+]i oscillations were recorded indirectly by monitoring the activity
      of apamin-sensitive Ca(2+)-activated K+ channels using the perforated patch-clamp
      technique and fast microperfusion system. Melatonin (1 nM) inhibited the
      initiation or attenuated the amplitude of oscillatory current responses induced
      by 10 nM GnRH in 72% of GnRH-sensitive cells. Analysis of the melatonin dose
      inhibition relationship showed that melatonin inhibited the initiation of [Ca2+]i
      oscillations with IC50 = 0.35 nM. In partially inhibited cells, melatonin reduced
      the GnRH-induced current amplitude by 55% on the average, prolonged the delay in
      onset of response to GnRH and decreased the frequency of oscillations. Once
      initiated by GnRH, the amplitude and frequency of oscillatory currents was
      inhibited by melatonin after a latency of 10-30 s. These effects of melatonin
      were fully reversible. After pretreatment of neonatal gonadotropes with pertussis
      toxin, no inhibition by melatonin was observed. The inhibitory effect of
      melatonin on initiation, amplitude and frequency of GnRH-induced oscillatory
      current persisted in the absence of external Ca2+. Melatonin alone did not induce
      any transmembrane current or membrane potential changes. These observations
      suggest that melatonin reduces GnRH-induced calcium mobilization from
      intracellular stores.

PMID- 9143000
TI  - Corticotropin-releasing hormone inhibits melatonin secretion in healthy
      volunteers--a potential link to low-melatonin syndrome in depression?
AB  - Interactions between the hypothalamic-pituitary-adrenocortical (HPA) system and
      melatonin secretion have been demonstrated, but only the effects of melatonin on
      the activity of the HPA system have been studied in man. Alterations of melatonin
      secretion described as low-melatonin syndrome have been demonstrated in patients
      suffering from a major depressive episode, and an inhibitory factor on melatonin
      secretion has been postulated. We investigated whether corticotropin-releasing
      hormone (CRH), which is thought to be involved in HPA abnormalities in depressed
      patients, can also suppress melatonin secretion in healthy volunteers. Ten
      healthy male human volunteers in a double-blind study design received randomized
      hourly intravenous injections from 08.00 to 18.00 h that contained 10 micrograms
      human CRH, 1 microgram adrenocorticotropic hormone (ACTH), or placebo to simulate
      pulsatile hormone secretion. Plasma melatonin and cortisol responses during the
      treatment and nocturnal sleep electroencephalograms after the treatment were
      recorded. Administration of CRH reduced melatonin secretion significantly below
      values obtained after administration of placebo and ACTH. Cortisol secretion was
      significantly enhanced by ACTH in comparison to both placebo and CRH.
      Electroencephalographic sleep parameters revealed no treatment effects. Our
      findings suggest that CRH has an inhibitory effect on the pineal secretion of
      melatonin in normal man. A mechanism via a release of cortisol was not supported
      by our results. Secondary hormonal effects from changes in nocturnal sleep
      architecture were excluded. Further investigation of the action of CRH on
      melatonin secretion as well as the mutual feedback between the HPA system and the
      pineal gland may extend our knowledge of neuroendocrine alterations mediating the
      adaptive response to stress and the eventual involvement in the pathogenesis of
      depression.

PMID- 9143001
TI  - Evidence for central nervous effects of corticotropin-releasing hormone on
      gastric acid secretion in humans.
AB  - In animals, corticotropin-releasing hormone (CRH) has been shown to decrease
      gastric acid secretion after intracerebral administration. Evidence exists that
      in man peptides have a direct access to the brain upon intranasal administration.
      This study aimed at assessing brain-mediated effects of CRH on gastric pH after
      intranasal administration in humans. Eleven healthy men were tested on 2
      occasions in a double-blind within-subject cross-over comparison during treatment
      with CRH (versus placebo) administered intranasally at a dose of 20 micrograms
      every 10 min. Gastric pH values were measured continuously by a gastral pH tube.
      After 2 h of intranasal treatment, 6 micrograms/kg pentagastrin was injected
      subcutaneously. The subject's mood was assessed by an adjective list (EWL-N) at
      the end of each experimental condition. Intranasal CRH increased pH baseline
      values from (mean +/- SE) 1.70 +/- 0.31 to 2.62 +/- 0.53 (corresponding to 54%),
      whereas during intranasal treatment with placebo pH values remained unchanged (p
      < 0.05). After injection of pentagastrin, pH values decreased to 0.73 +/- 0.04
      during placebo and to 0.93 +/- 0.14 during CRH treatment (n.s.). During treatment
      with CRH, subjects felt less tired (p < 0.05) and deactivated (p < 0.05). Plasma
      cortisol and CRH levels were not affected by intranasal CRH, excluding mediation
      of the CRH effects via resorption into the bloodstream, and TSH levels were
      slightly decreased by the end of the treatment. Results confirm the notion of a
      pathway for CRH from the nose to the brain, initiating, via central nervous
      mechanisms, inhibition of gastric acid secretion and a change of mood in humans.

PMID- 9143002
TI  - Immunohistochemical expression of retinoid X receptor isoforms in human
      pituitaries and pituitary adenomas.
AB  - Retinoid X receptors (RXRs) are transcriptional factors that belong to the
      steroid/thyroid hormone receptor superfamily. There are 3 RXR isoforms-alpha,
      beta, gamma-known to bind 9-cis-retinoic acid as their ligand. The expression of
      RXRs in human pituitary glands and pituitary adenomas has not been extensively
      investigated. To determine whether specific RXR isoforms may play roles in the
      state of differentiation of pituitary adenomas, we have investigated the
      immunohistochemical expression of RXR alpha and RXR gamma in 6 nontumorous
      pituitaries and in 60 different pituitary adenomas using isoform-specific
      antibodies. In the nontumorous pituitaries. RXR alpha was expressed in the nuclei
      of almost all cells, while RXR gamma was only expressed in thyrotropin (TSH)
      cells and in some cells positive for growth hormone (GH) and glycoprotein alpha
      subunit (alpha SU) but not in luteinizing hormone (LH) beta-subunit, follicle
      stimulating hormone (FSH) beta-subunit, prolactin (PRL) or adrenocorticotropin
      (ACTH) cells by double immunostaining. All 60 adenomas were RXR alpha positive,
      and 39 of 60 adenomas (65%) were positive for RXR gamma. The incidence of RXR
      gamma immunoreactivity in the different adenoma types was: 13 of 16 GH-producing
      adenomas (81.3%), 9 of 14 PRL-secreting adenomas (64.3%), 6 of 6 TSH-secreting
      adenomas (100%), 2 of 5 ACTH-secreting adenomas (40%) and 9 of 19 nonfunctioning
      adenomas (47.4%) including immunohistochemically gonadotropin-subunit-positive
      adenomas. The colocalization of RXR gamma with the TSH beta subunit, GH and alpha
      SU in the same adenoma cells was frequently observed, and sometimes RXR gamma was
      colocalized with PRL, ACTH, FSH beta or LH beta as shown by double
      immunostaining. We conclude that RXR alpha is expressed in both human pituitaries
      and pituitary adenomas. In contrast, RXR gamma is expressed more broadly in
      pituitary adenomas than in normal pituitaries and thus may play a role in the
      differentiation-specific cell types in the human pituitary both under
      physiological and pathological conditions.

PMID- 9143003
TI  - Metabolism of endothelin-1 by neuroblastoma x glioma hybrid (NG108-15) cells.
AB  - The endothelin (ET) peptides, ET-1, ET-2, and ET-3, as well as the ETA and ETB
      receptor subtypes, are known to occur in brain, but there is a dearth of
      information on the metabolism of these peptides by the central nervous system
      (CNS). In this study we have investigated the kinetics of ET-1 binding to and
      dissociation from the hybrid neuroblastoma x glioma cell line, NG108-15, which is
      known to contain functional ET receptors, and metabolism of bound ET-1. [125I]ET
      1 was incubated with cells for various periods of time up to 6 h, and the nature
      of the radioactivity in the cell medium and lysate was analyzed by reverse phase
      high performance liquid chromatography (HPLC). It was found that NG108-15 cells
      are capable of degrading [125I]ET-1 to [125I]Tyr and several fragments of
      intermediate hydrophobicity; however, a portion of the cell-associated [125I]ET-1
      was protected from degradation for several hours.

PMID- 9143004
TI  - The amplitude of quantal currents is reduced during short-term depression at
      neuromuscular synapses in Drosophila.
AB  - Focal extracellular excitatory postsynaptic currents were recorded to investigate
      short-term depression at glutamatergic Drosophila neuromuscular synapses. The
      amplitudes of quantal excitatory postsynaptic currents (qEPSCs) elicited before
      and after depolarizations eliciting large release were compared. Depression
      reduced the amplitude of the qEPSCs to 0.65 +/- 0.14 of control. Recovery from
      depression and of the receptor channels from desensitization follow a similar
      time course. Thus receptor desensitization seems to be involved in short-term
      depression at Drosophila neuromuscular junctions.

PMID- 9143005
TI  - Strychnine eliminates reciprocation and augmentation of respiratory bursts of the
      in vitro frog brainstem.
AB  - We have recorded rhythmic bursts of efferent action potentials from nerves of
      respiratory muscles in the frog (Rana pipiens), using a modified in vitro
      preparation, in which the brainstem lies in situ in the ventral half of the
      skull. The burst in the sternohyoid branch of the hypoglossal nerve (Hsh) was
      augmenting, and alternated with a relatively brief augmenting burst in the main
      branch of the hypoglossal nerve (Hm). The laryngeal branch of the vagus nerve
      (XI) displayed a biphasic burst, beginning before peak activity of Hsh and
      spanning the Hm burst. The spatio-temporal patterns of these bursts closely
      resemble those recorded from the same nerves in intact and in decerebrate frogs,
      indicating that the bursting rhythm of this in situ preparation constitutes
      fictive breathing. The nature of neurotransmission responsible for burst
      reciprocity and augmentation was investigated by applying the glycine receptor
      blocker, strychnine. Low levels of strychnine (1 and 5 M) increased the frequency
      of fictive breathing without changing the shape or timing of Hsh, Hm and XI
      bursts; at higher doses (10 and 20 M) the bursts in all nerves abruptly changed
      shape and timing to become synchronous and decrementing. The strychnine-induced
      changes were associated with the appearance of a prominent peak (10-20 Hz) on the
      spectral analysis of the nerve discharge, possibly indicating a fundamental
      change in neurogenesis of the respiratory pattern. We conclude that the burst
      augmentation and reciprocation discharge characteristics of fictive breathing in
      the frog require strychnine-sensitive inhibitory networks.

PMID- 9143006
TI  - Subretinal electrical stimulation of the rabbit retina.
AB  - A number of disorders results in photoreceptor degeneration, yet spare the inner
      retinal layers. We are investigating the possibility that retinal function may be
      restored in such a situation by electric current applied from the subretinal
      space. In the present study, bipolar strip electrodes receiving electric current
      from external photodiodes were implanted into the subretinal space of adult
      rabbits. Recordings were made from the scalp overlying the visual cortex in
      response to photic flash stimulation of one eye before surgery. This was compared
      to the visual cortex response caused by subretinal electrical stimulation of the
      same eye from an implanted strip electrode. Electric current to the strip
      electrode was provided by an externally connected photodiode that was stimulated
      at a remote location with a photoflash. The electrical stimulus was recordable as
      a brief electrical implant spike during stimulation. In addition, after the
      implant spike, cortical responses were obtained in response to subretinal
      electrical stimulation that resembled closely the normal light induced visual
      evoked potential produced by the pre-implanted eye. These results indicate that
      the visual system can be activated by electrical stimulation from the subretinal
      space and indicate that this approach may provide a means to restore vision to
      eyes blinded by outer retinal disease.

PMID- 9143007
TI  - Estrogen-excitable forebrain projections to the ventral premammillary nucleus of
      the female rat.
AB  - Retrograde labels by Nuclear Yellow from the female rat ventral premammillary
      nucleus (PMv) were most numerous in the lateral septum (LS) and the preoptic area
      (POA) and spread laterally into the substantia innominata. Other labels were in
      the diagonal band nucleus, the substantia innominata and the bed nucleus of the
      stria terminalis. Constant-current, single-pulse electrical stimulation of the
      PMv in urethane-anesthetized ovariectomized rats elicited antidromic action
      potentials in the cingulate cortex, in addition to the structures that contained
      labeled neurons. In the LS or cingulate cortex, but not in the POA, estrogen
      decreased antidromic activation thresholds and shortened refractory periods. The
      PMv is a way station that relays estrogen-excitable septal, but not preoptic,
      effects. The PMv also contains fibers of passage that originate in estrogen
      excitable cingulate neurons.

PMID- 9143008
TI  - Collateral projections from single neurons in the dorsal column nuclei to the
      inferior colliculus and the ventrobasal thalamus: a retrograde double-labeling
      study in the rat.
AB  - A number of single neurons in the dorsal column nuclei (DCN) and the sensory
      trigeminal nuclear complex were found to project to the thalamus and the inferior
      colliculus (IC). In the rats which were injected unilaterally with
      tetramethylrhodamine-dextran amine (TMR-DA) and Fluoro-Gold (FG) respectively
      into the posterolateral ventral thalamic nucleus and the external nucleus of IC,
      a number of neuronal cell bodies labeled retrogradely with both TMR-DA and FG
      were found throughout DCN contralateral to the injections. A few double-labeled
      neurons were also seen in the caudomedial part of the gracile nucleus ipsilateral
      to the injections. The double-labeled DCN neurons had relatively small cell
      bodies which are oval or fusiform in shape. When the injection sites in the
      thalamus extend into the posteromedial ventral thalamic nucleus, a few double
      labeled neuronal cell bodies were seen contralaterally in the trigeminal sensory
      nuclear complex, mainly in the caudal part of the interpolar spinal trigeminal
      nucleus.

PMID- 9143009
TI  - Oral administration of KW-5092, a novel gastroprokinetic agent with
      acetylcholinesterase inhibitory and acetylcholine release enhancing activities,
      causes a dose-dependent increase in the blood acetylcholine content of beagle
      dogs.
AB  - Acetylcholine (ACh) was detected in the blood and plasma of beagle dogs using a
      specific, sensitive radioimmunoassay. The mean basal ACh contents in the blood
      and plasma of beagle dogs were 451 +/- 65 and 83.5 +/- 12.3 pg/ml (+/- SEM, n =
      7), respectively, and were lower than the contents in humans reported previously
      by our laboratory. Oral administration of KW-5092 (10-30 mg/kg), a
      gastroprokinetic agent with acetylcholinesterase (AChE) inhibitory and ACh
      release enhancing activities, caused a dose-dependent increase in the ACh content
      of both the blood and plasma, as well as several behavioral side effects due to
      peripheral cholinergic stimulation. The size of the increase in the plasma ACh
      content at each dose of KW-5092 was greater than that in the blood, indicating
      that KW-5092 caused the increase in the blood ACh content through elevation of
      the plasma ACh content, by inhibition of AChE and facilitation of ACh release.
      These results demonstrate that the blood ACh of beagle dogs is present mainly in
      the blood cells and to a lesser degree in the plasma, and that KW-5092 increased
      the blood ACh content mainly by increasing the plasma ACh concentration.

PMID- 9143010
TI  - Influence of extracellular pH on inhibition by ifenprodil at N-methyl-D-aspartate
      receptors in Xenopus oocytes.
AB  - Ifenprodil is an atypical N-methyl-D-aspartate (NMDA) receptor antagonist that
      selectively blocks receptors containing the NR2B subunit. It has been proposed
      that ifenprodil may act at a stimulatory polyamine site on NMDA receptors,
      although interactions between ifenprodil and polyamines are non-competitive. NMDA
      receptors are also inhibited by extracellular protons, and an interaction between
      protons and polyamine stimulation has been described. Using voltage-clamp
      recording of recombinant NR1/NR2B receptors expressed in oocytes, ifenprodil
      inhibition was found to be pH sensitive with a smaller inhibition at alkaline pH.
      Similar effects of pH were seen on inhibition by nylidrin, eliprodil, and
      haloperidol, which are thought to act at the ifenprodil binding site. The pH
      sensitivity of ifenprodil block occurs at NR1B/NR2B as well as NR1A/NR2B
      receptors, suggesting that it is not influenced by the exon-5 insert that is
      present in NR1B but absent in NR1A. Protons may directly affect the ifenprodil
      binding site or may alter the coupling of ifenprodil binding to inhibition of
      channel gating.

PMID- 9143011
TI  - Protective effect of the antioxidant N-acetyl-L-cysteine in pneumococcal
      meningitis in the rat.
AB  - We investigated whether the antioxidant N-acetyl-L-cysteine or S
      methylisothiourea, an inhibitor of the inducible nitric oxide (NO) synthase, can
      modulate pathophysiological alterations in an advanced phase of experimental
      pneumococcal meningitis in the rat. N-acetyl-L-cysteine significantly attenuated
      the increase in brain water content, intracranial pressure and cerebrospinal
      fluid white blood cell count 24 h after infection as compared to untreated,
      infected rats. However, it had no effect on meningitis-associated disturbances in
      cerebrovascular autoregulation and CO2 reactivity of cerebral vessels. Treatment
      with S-methylisothiourea had no effect on the pathophysiological parameters
      measured in this model. These data suggest that reactive oxygen species, but not
      NO generated by the inducible NO synthase pathway, are key mediators of changes
      in brain water content, intracranial pressure and meningeal inflammation in an
      advanced stage of pneumococcal meningitis in the rat.

PMID- 9143012
TI  - Density ratio of dopaminergic versus serotonergic cells correlates with cone-to
      rod ratio in teleost retinas.
AB  - Dopaminergic and serotonergic cells were visualised immunohistochemically with
      antibodies against tyrosine hydroxylase and serotonin in retinal wholemounts of
      eight teleosts from different habitats and with different rod-to-cone ratios. The
      cell densities were calculated, and the density ratio of dopaminergic cells
      versus serotonergic cells was compared among these fish species. The density
      ratio was high (1.9-2.7) in three out of the four species of cichlid fish studied
      with cone densities roughly equalling rod densities, medium in roach (0.8) where
      rods dominate cone numbers, and low in deep-sea fish (0.2-0.4) with pure rod
      retinas. These observations confirm earlier findings on the species-specificity
      of the ratio of dopaminergic versus serotonergic cells in the retina and further
      demonstrate a close correlation between the rod-to-cone ratio, and the density
      ratio of dopaminergic versus serotonergic cells in the inner retina. The possible
      significance for the processing of photopic and scotopic information in the inner
      retina is discussed.

PMID- 9143013
TI  - Social stress induces high intensity sleep in rats.
AB  - We studied the effect of social stress on sleep electroencephalogram (EEG) in
      rats. Animals were subjected to a single social defeat by introducing them in the
      cage of an aggressive male conspecific for 1 h. The animals responded to the
      social conflict by a sharp increase in EEG slow-wave activity (SWA) during non
      rapid eye movement sleep (NREM) afterwards. Since SWA has been identified as an
      indicator of sleep intensity, the results suggest that acute stressors may
      accelerate the build up of sleep debt. Sleep intensity may, thus, not only depend
      on the duration of prior wakefulness but also on the nature of the waking
      experience. The strong increase in SWA after social defeat indicates that sleep
      may function to offset the mental loads imposed on the nervous system during
      wakefulness.

PMID- 9143014
TI  - Clinical presentation and patterns of regional cerebral atrophy related to the
      length of trinucleotide repeat expansion in patients with adult onset
      Huntington's disease.
AB  - We correlated trinucleotide CAG repeat numbers in the huntingtin gene with the
      regional brain atrophy and clinical phenotype in 23 adult autopsy cases of
      Huntington's disease (HD). CAG repeat number (39-56, mean 45.4 +/- 4.6)
      correlated inversely (P < 0.0001) with age at onset and death, but not with
      disease duration or initial symptoms. Cross-sectional areas of the striatum,
      pallidum, thalamus, amygdala, hippocampus, and the cortical grey and white matter
      within the frontal, temporal and parietal lobes at four levels (genu of the
      corpus callosum, amygdala, accumbens, hippocampus) were measured morphometrically
      from the coronal brain slices using image analysis. None of these morphometric
      variables correlated with number of CAG repeats. Thus, tissue atrophy in advanced
      HD is unrelated to the underlying genetic defect.

PMID- 9143015
TI  - NPY Y1 receptor like immunoreactivity exists in a subpopulation of beta-endorphin
      immunoreactive nerve cells in the arcuate nucleus: a double immunolabelling
      analysis in the rat.
AB  - Double immunolabelling immunohistochemistry in the arcuate nucleus of the rat
      demonstrates that neuropeptide Y (NPY) Y1 receptor like immunoreactivity is
      strongly present in a subpopulation of beta-endorphin immunoreactive nerve cell
      bodies, while the small NPY immunoreactive nerve cell bodies located medially
      lack NPY Y1 receptor like immunoreactivity. The NPY Y1 like immunoreactive nerve
      cell bodies lie in an arcuate area rich in NPY immunoreactive nerve terminals
      forming an uniform plexus. It is postulated that NPY Y1 receptors in beta
      endorphin neurons may mediate some actions of NPY on motivational processes and
      pain control as well as on hypophyseal hormone secretion, involving at the least
      in part a regulation of the tubero-infundibular DA neurons.

PMID- 9143016
TI  - Expression of dentatorubral-pallidoluysian atrophy (DRPLA) proteins in patients.
AB  - The genetic defect dentatorubral-pallidoluysian atrophy (DRPLA) is caused by
      expansion of a CAG trinucleotide repeat. The mutant gene is translated into
      protein whose electrophoretic mobility correlates to the number of expanded CAG
      trinucleotide repeats, indicating that the protein carries an expanded glutamine
      repeat. Using two polyclonal antibodies raised against the DRPLA gene product in
      immunoblotting, we determined the untruncated DRPLA proteins, and showed that the
      amounts of mutant and wild-type DRPLA proteins were similar in DRPLA brain
      tissues and lymphoblastoid cells, suggesting that regulation of the level of
      translation of the DRPLA gene is not central to the development of the disease.

PMID- 9143018
TI  - Age-related changes in the regulation of transcription factor NF-kappa B in rat
      brain.
AB  - Aging process involves an increase in stress at cellular level. We studied
      whether aging affects the regulation of stress responsive transcription factor NF
      kappa B in brain samples of Wistar rats. Hippocampus, cerebellum, and temporal
      and frontal lobes of cortex were studied. We observed a significant up-regulation
      in the constitutive, nucleus-located NF-kappa B binding activity in 30-month-old
      Wistar rats compared to young and 18-month-old rats. The increase was most
      prominent in cerebellum and in frontal cortex, but age-related changes did not
      occur in hippocampus. Inducible, cytoplasmic NF-kappa B binding activity was not
      affected by aging in any of the samples studied. Western blot assays did not show
      any age-related changes in the nuclear level of p50, p52, and p65 protein
      components of NF-kappa B complex. Cytoplasmic level of inhibitory I kappa B-alpha
      was also unaffected. The increase in nuclear constitutive NF-kappa B binding
      activity during aging may be related to the NF-kappa B driven cellular response
      to adapt neurons against apoptotic pressure, as observed recently in several
      apoptotic conditions.

PMID- 9143017
TI  - Influence of 5-HT1B/1D receptors on dopamine release in the guinea pig nucleus
      accumbens: a microdialysis study.
AB  - To clarify whether serotonin (5-HT) 5-HT1B/1D receptors are involved in dopamine
      (DA) release, extracellular levels of DA were monitored by in vivo microdialysis
      during various conditions. 5-HT (10 microM) alone, and together with the 5
      HT1B/1D receptor antagonist. GR127935 (10 microM), or the 5-HT1B/1D agonist,
      sumatriptan (1 microM), were perfused into the nucleus accumbens of freely moving
      guinea pigs. A 10-fold increase in the extracellular concentration of DA was
      obtained during administration of 5-HT alone. The 5-HT-induced DA elevation was
      not significantly affected by co-administration of sumatriptan (MANOVA; P > 0.05)
      but markedly attenuated by coperfusion of GR127935 (MANOVA; P = 0.02). Neither
      GR127935 nor sumatriptan, when administered alone, significantly affected
      extracellular DA levels. These results suggest that, in the DA-rich nucleus
      accumbens, 5-HT1B/1D receptors are not involved in the modulation of DA release
      during normal tonic or basal conditions but may take part in the regulation of DA
      release when synaptic 5-HT levels are very high.

PMID- 9143019
TI  - Distribution of the GABAA receptor complex beta 2/3 subunits in the brain of the
      frog Rana pipiens.
AB  - This report describes the distribution of labeling of the monoclonal antibody bd
      17 against the beta 2/3 subunits of the mammalian GABAA receptor complex
      throughout the brain of the frog Rana pipiens. The distribution matches quite
      closely those in homologous brain regions as previously described for this
      antibody in fishes, birds, and mammals, indicating that this antibody also labels
      beta 2/3 subunits of frog. A semiquantitative analysis of the distribution of
      labeling throughout the brain is based upon relative optical densities with
      respect to the structure showing maximal optical density in each brain, using
      standard illumination conditions. Comparison with distributions in birds and
      mammals suggests that these GABAA receptor complex subunits are strongly
      conserved in vertebrate evolution and play an important role in the visual,
      auditory, olfactory and motor systems.

PMID- 9143020
TI  - Zinc transport in the rat olfactory system.
AB  - To study zinc (Zn) mobility in the rat olfactory tract, brain distribution of
      65Zn after injection into the olfactory bulb or amygdaloid nuclei was analyzed by
      autoradiography. Twenty-four hours after 65Zn injection into the olfactory bulb,
      65Zn was distributed in the ipsilateral piriform cortex, amygdaloid nuclei and
      the anterior commissure. Moreover, in the case of injection of a higher level of
      65Zn into the olfactory bulb, 65Zn was distributed in the ipsilateral entorhinal
      cortex in addition to the above regions. Twenty-four hours after 65Zn injection
      into the amygdaloid nuclei, 65Zn was distributed in the ipsilateral piriform and
      entorhinal cortex. These results suggest that Zn is intraneuronally transported
      along the olfactory tract. Zn may be taken up by the piriform neurons after
      release from the secondary olfactory neuron terminals and transported to the
      entorhinal area.

PMID- 9143021
TI  - Monoclonal antibodies against mouse splenic stromal cells.
AB  - A panel of rat monoclonal antibodies directed against mouse splenic stromal cells
      were isolated. These monoclonal antibodies were immunohistochemically divided
      into four groups which reacted with non-lymphoid cells of the murine spleen; (I)
      in the white pulp, (II) at the marginal zone, (III) in the red pulp, and (IV) on
      the endothelium of splenic blood vessels. These monoclonal antibodies were
      studied immunohistochemically in lymphoid organs by means of light and electron
      microscopy. Monoclonal antibodies SS-4 (group I) reacted with fibroblastic
      reticulum cells that were distributed only in the white pulp of the spleen and in
      the follicular areas of lymph nodes. The SS-4 staining cell, in clustered splenic
      stromal cells, formed colonies which included a small number of Thy-1 positive
      lymphocytes. Therefore, we concluded that SS-4 staining stromal cells comprise
      the lymphoid compartment. In contrast, monoclonal antibodies SS-1, SS-3 and SS-5
      (group II) reacted with dendritic shaped cells in the marginal zone of the
      spleen. Examination of splenic extramedullary hematopoiesis in mice rescued by
      bone marrow transplantation after lethal irradiation revealed that SS-3 and SS-5
      reacted with dendritic shaped stromal cells in clonal nodules of engrafted marrow
      in the red pulp. SS-3 and SS-5 staining cells could not be observed in
      physiologic hematopoiesis of non-transplanted mice. It was suggested that SS-3
      and SS-5 staining stromal cells are involved in primitive hematopoiesis.
      Monoclonal antibodies SS-2, SS-6 and SS-7 (group III) mainly reacted with
      dendritic cells and macrophages in the red pulp. Monoclonal antibodies SS-B and
      SS-9 (group IV) reacted with endothelial cells of blood vessels and sinuses.
      These findings of heterogeneity in mouse splenic stromal cells are further
      evidence that specific micro-environments are composed by specialized stromal
      cells.

PMID- 9143022
TI  - Contribution of cell proliferative activity to malignancy potential in testicular
      seminoma.
AB  - Testicular anaplastic seminoma, which has a high mitotic activity, is regarded as
      more malignant than typical seminoma, although its prognosis is still unclear. To
      determine whether seminoma with relatively greater malignancy potential can be
      identified based on the cell proliferative activity, the mitotic rate (MR;
      mitotic count per high-power field), mitotic index (MI; mitotic count per 1000
      cells), Ki-67 labeling index (Ki-67 LI; the percentage of positive cells) and
      proliferating cell nuclear antigen LI (PCNA LI; the percentage of positive cells)
      were histologically examined in 44 patients. The MI, Ki-67 LI and PCNA LI in
      patients with metastatic disease were significantly higher than those in patients
      without metastatic disease, and the MI in patients with fatal disease was
      significantly higher than those in patients cured of the disease. However, these
      distributions of the MI, Ki-67 LI and PCNA LI values overlapped for both pairs of
      groups. There were no significant differences in the MR. These results suggest
      that the cell proliferative activity makes a small contribution to the malignancy
      potential in testicular seminoma, with the activity being not necessarily
      indicative of metastasis and prognosis.

PMID- 9143023
TI  - Immunohistochemical analysis of the nm23 gene products in testicular seminoma.
AB  - The nm23 gene has been identified as a metastasis suppressor gene. To clarify the
      role of nm23 as a metastasis suppressor gene in testicular seminoma, the
      expression of the nm23-H1 and -H2 proteins (human nucleoside-diphosphate kinase-A
      and -B) was immunohistochemically examined in 43 patients. Thirty-six (84%) and
      21 (49%) of the 43 primary tumors were positive for the nm23-H1 and -H2 proteins,
      respectively. There was no significant difference in either nm23-H1 or -H2
      expression between the 24 primary non-invasive tumors and the 19 primary invasive
      tumors, or between the 31 primary tumors without metastasis and the 12 primary
      tumors with metastasis. In all, and 5 of 6 metastatic tumors, the expression of
      nm23-H1 and -H2 proteins was observed, respectively, and the expression was not
      decreased in the metastatic tumors, compared to the primary tumors. In
      conclusion, the immunohistochemical expression of both the nm23-H1 and -H2 gene
      products is not associated with the metastatic status or the invasive status of
      testicular seminoma, and it is unlikely to be a useful non-metastatic indicator
      for testicular seminoma. Further studies are needed to elucidate the biological
      role of nm23.

PMID- 9143024
TI  - Clinicopathological analysis on cancers of autopsy cases in a geriatric hospital.
AB  - It is generally accepted that cancers in the elderly are of low grade malignancy.
      In order to clarify this point, autopsy cases from a medical center for the
      elderly between 1982 and 1994 were pathologically analyzed. Three hundred and
      fifty (160 males, 190 females) out of a total of 871 (361 males, 510 females)
      autopsy cases were examined. The incidence of cancer in various age groups were
      found to be as follows: < or = 69 years, 24/67 (36%); 70-74 years, 40/102 (39%);
      75-79 years, 54/136 (39%); 80-84 years, 79/180 (44%); 85-89 years, 66/172 (38%);
      90-94 years, 59/137 (43%); 95-99 years, 17/56 (30%); and > or = 100 years, 12/21
      (57%). The incidences did not significantly differ among the groups, that is,
      there was no age-dependency in the incidence of cancer. Furthermore, the
      incidences of multiple cancers (two or more different malignancies in one
      patient) also did not differ. However, deaths due to the cancers showed a
      tendency to decrease with age. The survival periods of clinical cancer cases
      without a surgical operation history (time period between the date of diagnosis
      and death), were age-related for female cases. However, the rate of distant
      metastasis was not age-related. The incidence of latent cancers in individuals
      over 85 years of age was 79/174 (45.4%) and significantly higher than the value
      of 69/234 (29.5%) for those under 85. The number of malignant tumors in various
      organs for the different age groups was also counted and the total numbers of
      clinical cancers and latent cancers in each organ were, 50 and 23 in the lung, 46
      and 20 in the stomach, 41 and 31 in the colon, 0 and 39 in the prostate, and 14
      and 0 in the mammary glands, respectively. All prostate cancers were latent
      cancers, and all mammary cancers were clinical cancers. These findings provide
      strong evidence that cancers in individuals of advanced age have less malignancy
      potential.

PMID- 9143025
TI  - Comparative morphometric study of immunohistochemical versus conventional
      staining for the evaluation of megakaryocytopoiesis in normal and pathological
      bone marrow biopsies.
AB  - Identification of megakaryocytes by immunohistochemistry may be superior to
      hematoxylin-eosin (HE) stain method for assessing megakaryocyte size and number
      in clinical specimens; however, a side-by-side comparison of the two methods has
      not been reported. In the present study, comparative morphometry using both
      methods was performed on marrow biopsies of normal individuals, and of patients
      with myelodysplastic syndrome, chronic myeloid leukemia and immune
      thrombocytopenia. Morphometric results in the present study showed that precise
      megakaryocyte size can be calculated in normal and pathologic bone marrow
      sections by using HE stain if one employs stereological corrections. In contrast,
      megakaryocyte numbers can be more precisely detected by immunohistochemistry than
      by HE stain, particularly in myelodysplastic syndrome and chronic myeloid
      leukemia. Differentiation disturbances and ineffective megakaryocytopoiesis in
      myelodysplastic syndrome were demonstrated by immunomorphometric analyses.

PMID- 9143026
TI  - Gastrointestinal autonomic nerve tumors: immunohistochemical and ultrastructural
      studies in cases of gastrointestinal stromal tumor.
AB  - The gastrointestinal autonomic nerve tumor (GAN tumor) is an uncommon stromal
      tumor with a morphological feature resembling the cell processes of the enteric
      plexus, and was originally termed a plexoma or plexosarcoma. Light microscopic
      studies show the GAN tumor most often consists of spindle-shaped cells
      indistinguishable from a smooth muscle tumor or Schwann cell tumor.
      Immunohistochemical and ultrastructural examinations of 18 cases of
      gastrointestinal stromal tumor (GIST) were performed. During ultrastructural
      examination, all of the 12 cases which were immunohistochemically positive for S
      100 protein or neuron-specific enolase (NSE) showed synapse-like structures
      containing dense core neurosecretory granules measuring 100-200 nm, and 40-60 nm
      endocytoplasmic vesicles. These results suggest that most GIST of neurogenic
      origin are tumors derived from the myenteric nerve plexus.

PMID- 9143027
TI  - Pigmented variant of benign oncocytic lesion of the pharynx.
AB  - A case of pigmented variant of benign oncocytic lesions is reported. The lesion
      was incidentally found in the pharynx of a 69-year-old man, and the gross
      appearances were multiple, small, flat elevations with black discoloration.
      Microscopically, ducts of seromucinous glands were replaced by melanin-containing
      oncocytes and adjacent dendritic melanocytes. To date, such a pigmented variant
      of benign oncocytic lesion has not been reported before.

PMID- 9143028
TI  - Sarcomatoid hepatocellular carcinoma with osteoclast-like giant cells: case
      report and immunohistochemical observations.
AB  - Hepatocellular carcinoma (HCC) with osteoclast-like giant cells (OGC) developed
      in the cirrhotic liver of a 42-year-old male. Serum protein induced by vitamin K
      absence or antagonist II was elevated preoperatively. The patient died of the
      disease on the 28th postoperative day. Histologically, the tumor consisted of OGC
      and mononuclear cells (MC). The OGC were characterized by benign-appearing
      nuclei, whereas the MC had atypical nuclei with a considerable number of mitoses.
      A vaguely trabecular pattern was observed in the focal area of the tumor, but no
      evidence of overt HCC was found. Immunohistochemical analysis revealed that both
      OGC and MC were diffusely positive for histiocytic and mesenchymal markers. Some
      MC were focally positive for cytokeratins 7, 8 and 19, and for albumin. Our
      clinical, histological and immunohistochemical findings suggest that the MC were
      derived from hepatocytes, with some mesenchymal features, but the OGC were non
      neoplastic and reactive histiocytes.

PMID- 9143030
TI  - Recommendations for the reporting of urinary bladder specimens containing bladder
      neoplasms. Association of Directors of Anatomic and Surgical Pathology.
AB  - The Association of Directors of Anatomic and Surgical Pathology have developed
      recommendations for the surgical pathology reporting of common malignant tumors.
      The recommendations for carcinomas of the urinary bladder are reported herein.

PMID- 9143029
TI  - Juvenile granulosa cell tumor discovered during pregnancy: case report with
      immunohistochemical study of steroidogenesis.
AB  - A multilobular cystic juvenile granulosa cell tumor in a 33-year-old pregnant
      woman was examined. Pathological examination of the specimen at Cesarean section
      at 38 weeks of gestation revealed three different histological patterns; diffuse
      proliferation, trabecular or cord-like proliferation, and characteristic
      microfollicular patterns, as well as the presence of numerous luteinized stromal
      cells. These histological patterns were intermingled and transference among these
      patterns was detected. Immunoreactivity of steroidogenic enzymes including
      cholesterol side-chain cleavage, 3 beta-hydroxysteroid dehydrogenase and 17 alpha
      hydroxylase was detected only in luteinized stromal cells. However, that of
      adrenal 4 binding protein, a transcription factor of steroidogenesis, was present
      in almost all the tumor cells as well as luteinized stromal cells, suggesting
      that tumor cells acquired the potential of metabolizing and synthesizing steroid
      hormones. The hormonal environment associated with pregnancy altered the
      histological and biological features of this juvenile granulosa cell factor.

PMID- 9143031
TI  - Comments regarding the American Association of Directors of Anatomic and Surgical
      Pathology (ADASP) recommendations for the reporting of urinary bladder specimens
      containing bladder neoplasms: comparison with the Japanese General Rule for
      Clinical and Pathological Studies on Bladder Cancer.

PMID- 9143032
TI  - Origin of intraepithelial apoptotic cells in human colorectal adenomas.
AB  - The origin of intraepithelial apoptotic cells in human colorectal adenomas was
      examined using immunohistochemistry. Tissue sections of human colorectal adenomas
      obtained during surgery or endoscopy were stained by the streptavidinbiotin
      method using antibodies against carcinoembryonic antigen (CEA) and leukocyte
      common antigen (LCA). Approximately 15.7% of apoptotic bodies stained positive
      for CEA with immunoreactivity on the cytoplasm, whereas all cells stained
      negative for LCA. These findings suggest that intraepithelial apoptosis in human
      colorectal adenomas originates from adenoma cells rather than infiltrating
      lymphocytes as previously proposed, and that apoptotic cells maintained their
      cytoplasmic antigenicity in the early stages of apoptosis.

PMID- 9143033
TI  - Subcellular organelle analysis applying confocal laser scanning microscopy to the
      steroid-producing epithelial ovarian tumor: a technical note.
AB  - An epithelial ovarian tumor with steroid production was examined in a 70-year-old
      postmenopausal female. The stromal cells of this tumor were rather dense and
      occasionally characterized by luteinization or hyperthecosis, which has been
      associated with steroidogenesis. Subcellular visualization using confocal laser
      scanning microscopy (CLSM) successfully led to the identification of 3 beta
      hydroxysteroid dehydrogenase (HSD) in both mitochondria-like small particles and
      endoplasmic reticulum-like linear profiles, and P450-aromatase also in
      endoplasmic reticulum-like linear profiles, on the three-dimensional images.

PMID- 9143034
TI  - Subretinal hemorrhages in proliferative diabetic retinopathy.
AB  - PURPOSE: To describe the clinical features of patients with advanced
      proliferative diabetic retinopathy who underwent vitrectomy and were found to
      have subretinal hemorrhages. METHODS: The authors conducted a retrospective study
      of 49 patients with complications of proliferative diabetic retinopathy requiring
      pars plana vitrectomy and demonstrating the presence of subretinal hemorrhage.
      Preoperative, intraoperative, and postoperative clinical characteristics were
      evaluated. Patients were observed for a minimum of 6 months. RESULTS: The
      location, size, and clearance of subretinal hemorrhages revealed wide variation.
      Forty-two patients had focal subretinal hemorrhages, and 14 patients within this
      group had submacular hemorrhages. A retinal break was observed in 15 patients
      (31%). Only one patient required drainage of the subretinal hemorrhage to achieve
      retinal reattachment. Vitreous surgery resulted in 59% of patients achieving a
      visual acuity > or = 5/200. Seventy-nine percent had stable or improved vision,
      whereas 20% had worse vision after surgery. CONCLUSION: Subretinal hemorrhages
      appear to be an uncommon feature associated with long-term, advanced
      proliferative diabetic retinopathy and portend a guarded visual prognosis. These
      hemorrhages may occur spontaneously in previously untreated eyes and are often
      unsuspected until observed at the time of vitreous surgery. In general, removal
      of subretinal hemorrhages was not necessary to achieve macular anatomic
      attachment, and most patients experienced improved visual function after surgery.
      Diabetic subretinal hemorrhages may indicate a retinal break, and, therefore,
      careful ophthalmic inspection should be performed in these patients.

PMID- 9143035
TI  - Surgical removal of subfoveal neovascularization in idiopathic juxtafoveolar
      retinal telangiectasis.
AB  - PURPOSE: To investigate the efficacy of the surgical removal of subfoveal
      choroidal neovascularization in patients with type 2A idiopathic juxtafoveolar
      retinal telangiectasis. METHODS: Two patients with bilateral acquired idiopathic
      juxtafoveolar retinal telangiectasis and a subfoveal choroidal neovascular
      membrane underwent surgical excision of the membrane using standard subretinal
      surgical techniques. RESULTS: In both cases, surgical removal of the neovascular
      membrane was complicated by an intimate adherence of the membrane with the
      overlying neurosensory retina in an area of retinochoroidal anastomosis. A
      retinal dehiscence occurred in both instances at the time of surgery.
      Postoperative visual outcome was poor. CONCLUSION: The retinochoroidal
      anastomoses often visualized in cases of subretinal neovascularization
      complicating bilateral acquired IJFRT could indicate that there is a fairly
      marked adherence of the neovascular membrane to the neurosensory retina. Attempts
      at surgical removal of subretinal membranes in this disease entity with current
      techniques may be contraindicated.

PMID- 9143036
TI  - Postoperative posterior retinal holes after pars plana vitrectomy for primary
      retinal detachment.
AB  - BACKGROUND: Although retinal breaks occur frequently during vitrectomy, the
      postoperative occurrence of new retinal holes close to the vascular arcade after
      vitrectomy for rhegmatogenous retinal detachment rarely has been reported.
      METHODS: Three patients with rhegmatogenous, retinal detachment were treated by
      vitrectomy. More than 49 days after vitrectomy, posterior retinal holes with no
      retinal detachment occurred halfway between the vascular arcade and the
      chorioretinal scar around the extrusion hole or the primary retinal tear.
      RESULTS: These new holes were effectively managed with photocoagulation.
      CONCLUSION: New hole formation could be caused by the technique of the internal
      drainage, the contraction of the photocoagulation scar, or epiretinal membrane
      contraction. Another possibility is that new holes occur through two opposite
      tangential traction contractile forces: one induced by the contraction of the
      photocoagulation scar, the other caused by the contraction of the premacular
      cortical vitreous attached to the vascular arcade.

PMID- 9143037
TI  - Ocular siderosis. Diagnosis and management.
AB  - PURPOSE: To assist clinicians in the diagnosis and management of ocular
      siderosis. METHODS: The diagnosis and management of three cases of ocular
      siderosis secondary to a retained iron-containing intraocular foreign body are
      described. RESULTS: Noteworthy features included: 1) the characteristic features
      of a tonic or Adies pupil (one case) and 2) the failure of high-resolution
      computed tomography scanning and plain film radiography to detect the intraocular
      foreign body (two of three cases). In contrast, ultrasonography demonstrated the
      intraocular foreign bodies in all cases and accurately localized them to the
      inferior retinal quadrants. A third noteworthy finding was that a preoperative
      electroretinogram reduction in amplitudes of as much as 40% compared with that of
      the uninvolved eye was compatible with excellent vision, and that the
      electroretinogram returned to normal after the intraocular foreign body was
      removed. CONCLUSIONS: Ocular siderosis should be considered in the differential
      diagnosis of a tonic or Adies pupil. To detect an occult intraocular foreign
      body, clinicians should not rely exclusively on computed tomography scanning or
      plain film radiography, but should also use B-mode echography with careful study
      of the inferior quadrants. In ocular siderosis a preoperative electroretinogram
      reduction in amplitudes of as much as 40% may be reversible after intraocular
      foreign body removal.

PMID- 9143038
TI  - Ultrasonically induced hyperthermia for adjunctive treatment of intraocular
      malignant melanoma.
AB  - PURPOSE: This report describes results of a prospective pilot trial to evaluate
      the safety and efficacy of hyperthermia as an adjunct to enucleation or
      brachytherapy in the treatment of patients with intraocular malignant melanoma.
      METHODS: Twenty-five patients with intraocular malignant melanomas were treated
      with ultrasonically induced hyperthermia. In 14 patients, hyperthermia was
      administered before enucleation (median follow-up period, 44 months), and in 11
      patients, hyperthermia was used as an adjunct to brachytherapy (median follow-up
      period, 79 months). RESULTS: Patient survival in each group was compared with
      that of a control group treated with enucleation or brachytherapy alone, using
      Kaplan-Meier and Cox analysis. Taking into account the simultaneous effects of
      tumor size and location, the relative risk ratios and 95% confidence bounds
      associated with adjunctive hyperthermia were 1.68 (range, 0.60-4.72) and 0.68
      (range, 0.16-2.89) for the enucleation and brachytherapy groups, respectively.
      CONCLUSIONS: Patients receiving adjunctive hyperthermia with brachytherapy showed
      increased survival, whereas those receiving hyperthermia before enucleation
      showed decreased survival. Neither trend was statistically significant in this
      small series. The synergism of hyperthermia with radiation may offer the
      possibility of improved tumor management.

PMID- 9143039
TI  - Ophthalmic, ultrasonographic findings in primary central nervous system lymphoma
      with ocular involvement.
AB  - PURPOSE: To describe and classify ophthalmic, ultrasonographic findings in
      patients with primary central nervous system lymphoma with ocular involvement.
      METHODS: B- and A-scan ultrasonography was performed on the eyes of 13 patients
      with primary central nervous system lymphoma with ocular involvement. RESULTS: In
      seven patients, the eyes were the site of initial involvement. In the other six
      patients, both ocular and central nervous system disease were present at the
      initial evaluation. All patients had abnormal ultrasonographic findings. The most
      common were vitreous debris (n = 10), choroidal-scleral thickening (n = 6), and
      widening of the optic nerve (n = 4). Elevated chorioretinal lesions (n = 3) and
      retinal detachment (n = 2) were also found. CONCLUSION: Ophthalmic
      ultrasonography is a useful adjunctive diagnostic technique for characterizing
      ocular involvement in lymphoma. Ocular lymphoma may present as chorioretinitis,
      vitreitis and nonspecific uveitis; it produces characteristic, but nonspecific
      findings on ultrasonography. The diagnosis of ocular involvement is an important
      factor in determining treatment.

PMID- 9143040
TI  - Morphologic studies of the peripheral vitreoretinal interface in humans reveal
      structures implicated in the pathogenesis of retinal tears.
AB  - PURPOSE: The ultrastructural nature of the preequatorial vitreoretinal interface
      was studied to elucidate the predisposing role for peripheral retinal tear
      formation. METHODS: Fourteen enucleated globes from seven decreased patients were
      examined. The patients ranged in age from 16-88 years, with an average age of 40
      years. None of the patients had a history of ocular or systemic disease that
      could have affected the eyes. Globes were examined by stereomicroscopy and by
      light and electron microscopy using the celloidin embedding method. RESULTS: On
      examination we found several structures in addition to tufts and rosettes. In the
      vitreous cortex, fibrillar structures with no vitreoretinal attachment to the
      retina frequently were found. We propose that these structures be called "tubuli"
      because of their spiral appearance. Mushroom-like structures, which we propose be
      referred to as "spiculae," were found to arise from the intact internal limiting
      lamina of the retina and to insert into the vitreous cortex, constituting foci of
      vitreoretinal adhesion. Other structures, which we propose be called "verrucae,"
      arose from the disrupted internal limiting lamina of the retina and inserted into
      disrupted areas of vitreous cortex. CONCLUSIONS: Tubuli appear to be remnants of
      the embryonic vasculature with no clinical or pathologic significance. Because of
      their pattern of inserting into the internal limiting lamina of the retina and
      the peripheral vitreous cortex, spiculae and verrucae may play an important role
      in the formation of retinal breaks.

PMID- 9143041
TI  - Clinical and ultrasound study of peripheral vitreoretinal adhesions.
AB  - PURPOSE: To evaluate the frequency of peripheral vitreoretinal adhesions in the
      region of the vitreous base by ultrasound examination in relation to axial length
      of the eye and the age of the patient. Patient gender and the presence of visual
      symptoms also were considered. METHODS: A total of 228 consecutive patients (445
      eyes) underwent biometry, ultrasound examination, and biomicroscopic fundus
      examination. Their medical history also was taken. The patients were divided into
      three groups according to axial length of the eye (< 24 mm, 24-26.5 mm, and >
      26.5 mm) and into three age groups (20-40 years, 41-60 years, and > 60 years).
      RESULTS: No correlations was found between peripheral vitreoretinal adhesions and
      gender or between peripheral vitreoretinal adhesions and axial length of the eye.
      A significant correlation was found between peripheral vitreoretinal adhesions
      and age (P < 0.001). The proportion of adhesions increased with age (P < 0.001).
      The association between adhesions and presence of symptoms also was significant
      (P < 0.001). Multivariate analysis showed that only the presence of symptoms
      independently correlated with adhesions (relative risk, 1.71, 95%; confidence
      interval, 1.19, 2.46). CONCLUSION: Our study shows that peripheral vitreoretinal
      adhesions, detected by ultrasound, were always associated with the presence of
      symptoms.

PMID- 9143042
TI  - Morphometric analysis of pars plana development in humans.
AB  - BACKGROUND: Quantitative features of pars plana development in humans are not
      well characterized. Knowledge of the dimensions of this region is important for
      our understanding of the anatomy of infant eyes for the purposes of surgery. The
      purpose of this study was to provide a morphometric description of pars plana
      growth in relation to 1) postconceptional age and 2) axial length. METHODS: We
      reviewed histologic specimens from 204 human eyes of postconceptional ages
      ranging from 10 weeks to 5 years. Axial length and temporal pars plana width were
      measured directly with a reticule system. The relationships among pars plana
      width, axial length, and postconceptional age were examined. RESULTS: The most
      rapid phase of pars plana growth occurred between 26 weeks and 35 weeks
      gestation. A linear relationship between pars plana width and axial length
      existed once the axial length reached 12 mm (correlation coefficient = 0.918; P =
      0.0001). In infants of 38-42 weeks postconceptional age, mean pars plana width
      was 1.87 mm (range, 0.9-2.8 mm; standard direction = 0.48 mm), and mean axial
      length was 17.7 mm (range, 15-23 mm; standard direction = 1.9 mm). After the age
      of 62 weeks postconception, all eyes had a temporal pars plana width > or = 3 mm
      and an axial length > or = 19 mm. The estimated age at which there was a 95%
      chance of the pars plana width being > or = 3 mm was 64.4 weeks (95% fiducial
      confidence limits, 60.8-86.2 weeks). CONCLUSIONS: The pars plana first develops
      during the second trimester of gestation. A rapid growth phase occurs between 26
      weeks and 35 weeks postconception. The dimensions of the pars plana are
      correlated closely with axial length and postconceptional age. Assuming that a
      pars plana width of 3 mm is required for surgery to be performed via a pars plana
      approach, we estimate that pars plana vitreous surgery can be performed when the
      patient is at least 62 weeks old (postconception), which is a 6-month-old full
      term infant.

PMID- 9143043
TI  - Experimental pseudomonal posttraumatic endophthalmitis in a swine model.
      Treatment with ceftazidime, amikacin, and imipenem.
AB  - PURPOSE: To compare the intravitreal efficacy of three separately administered
      antibiotics (imipenem, ceftazidime, and amikacin) in limiting the intraocular
      inflammation and tissue destruction caused by posttraumatic pseudomonal
      endophthalmitis. METHODS: Thirty-three Yorkshire pigs each received a surgically
      induced scleral injury to the right eye. After repair, each eye was injected with
      22,000 colony-forming units of live Pseudomonas aeruginosa. Pigs then were
      randomly grouped into a natural-history-of-infection group in which no treatment
      was given (n = 9) or into groups treated with the following: intravitreal
      imipenem (n = 6), ceftazidime (n = 6), amikacin (n = 6), or normal saline (n =
      6). Pigs then were observed clinically for 18-24 hours after surgery and
      enucleated for histopathologic examination. RESULTS: Clinical examinations
      revealed significantly less posterior segment inflammation in pigs treated with
      amikacin and imipenem than in pigs in the natural history or saline control
      groups, based on the Wilcoxon rank sum test (P < .05). Histopathologic
      examinations showed similar results, with less intraocular inflammation and
      retinal destruction in pigs treated with amikacin and imipenem, whereas the
      inflammation in pigs treated with ceftazidime did not differ significantly from
      that in control pigs. CONCLUSION: Intravitreal antibiotic treatment with imipenem
      or amikacin appears to limit intraocular inflammation and retinal tissue damage
      when given early in the course of posttraumatic pseudomonal endopthalmitis.
      Results with ceftazidime are less conclusive.

PMID- 9143044
TI  - Experimental vitreous and aqueous replacement with perfluorophenanthrene.
      Clinical, histologic, and electrophysiologic results.
AB  - PURPOSE: Anterior and posterior segment changes of experimental vitreous and
      aqueous substitution with Perfluorophenanthrene were evaluated. METHODS: In 28
      rabbit eyes that underwent vitrectomy, tamponades of 1.2 cc Perfluorophenanthrene
      remained as long as 8 weeks under clinical and electrophysiologic control.
      Histologic examinations of the eyes were done 1, 2, 4, and 8 weeks after
      insertion of the tamponade. In an additional 15 rabbit eyes,
      Perfluorophenanthrene was injected into the anterior chamber, and in some cases
      it was removed after 2 and 4 weeks, respectively. Follow-up examinations, which
      were done no later than 12 weeks after injection, included clinical appearance,
      endothelial cell counts, corneal pachymetry, tonometry, and histopathology.
      RESULTS: Histologically we found narrowing of the outer plexiform layer and
      single macrophages in the inferior retina after 2 weeks. Cell loss in the outer
      nuclear layer and wrinkling of the outer retinal layers were observed after 4
      weeks, which lead to the development of irregularities of all layers inferiorly
      after 8 weeks. Electroretinograms showed unchanged b-wave amplitudes after
      maximal light stimulation at each examination, but separate interpretation of low
      light intensity responses showed a significant decrease in b-wave amplitudes 4
      weeks after surgery. Anterior segment intolerance started with stromal edema on
      the second day after surgery; corneal vascularization and scar formation occurred
      subsequently. Inferior endothelial cell density decreased to about 50%.
      Histologically inflammatory reactions, vacuolization of the inferior trabecular
      meshwork, and closure of the chamber angle between 5 and 7 o'clock were observed.
      CONCLUSIONS: Perfluorophenanthrene is only suitable for very short-term vitreous
      replacement unless prolapsing into the anterior chamber. Damages to the retina
      were observed 2 weeks after surgery.

PMID- 9143045
TI  - Diagnostic and therapeutic challenges.

PMID- 9143046
TI  - Combined hamartoma of the retina and retinal pigment epithelium associated with
      epiretinal membrane and macular hole.

PMID- 9143047
TI  - Noninfectious branch retinal vein occlusion in HIV-positive patients.

PMID- 9143048
TI  - Accidental ocular perforation from self-inflicted facial palsy.

PMID- 9143049
TI  - Prepapillary vascular loop and a recurrent vitreous hemorrhage.

PMID- 9143050
TI  - Major blinding complication of acquired immune deficiency syndrome (AIDS)

PMID- 9143051
TI  - Examination and treatment of patients with pediatric retinal disease.

PMID- 9143052
TI  - Patients undergoing vitreous surgery under local anesthesia.

PMID- 9143053
TI  - Interstitial brachytherapy procedures for brain tumors.
AB  - Promising results have been obtained using brachytherapy in the treatment of
      brain tumors. Very low-dose rate brachytherapy (60-100 Gy given at 0.05-0.10
      Gy/h) has been used for low-grade gliomas, resulting in 5- and 10-year survival
      probabilities of 85% and 83% for pilocytic astrocytomas and 61% and 51% for grade
      II astrocytomas. Only 2.6% of patients had symptomatic radiation necrosis. For
      faster-growing high-grade gliomas, temporary implants delivering about 60 Gy at
      0.40-0.60 Gy/h are generally used. The largest series have reported median
      survival times of 12-13 months after brachytherapy for recurrent malignant
      gliomas and 18-19 months after diagnosis of primary glioblastomas treated with
      external beam radiotherapy and brachytherapy boost. A recent prospective,
      randomized trial demonstrated significantly improved survival for high-grade
      glioma patients who had brachytherapy boost. However, over 50% of patients who
      undergo brachytherapy for malignant gliomas require reoperation for tumor
      progression and/or radiation necrosis. Strategies are under development to
      improve local control without increasing radiation toxicity.

PMID- 9143054
TI  - Brachytherapy in primary ocular tumors.
AB  - Patients with primary ocular tumors are seen infrequently in the medical
      profession, and most of these patients are referred to specialty centers which
      has resulted in a good study population. In the past, ocular tumors were treated
      with enucleation, but the current emphasis is now on organ preservation with
      sparing of all or partial visual acuity. In the management of these tumors,
      plaque brachytherapy and particle beam therapy have been used more frequently as
      an alternative to enucleation. A multi-institutional study, the Collaborative
      Ocular Melanoma Study (COMS), is currently underway, organized by the National
      Eye Institute. The COMS isotope of choice is Iodine-125 (I-125). Recurrence after
      plaque therapy is approximately 15%, although it may be as high as 37% at 15
      years for metastatic disease. In one study, nondiffuse iris melanoma has been
      controlled in 93% of patients by custom plaques utilizing I-125. Plaque
      brachytherapy also utilizes I-125 for the treatment of retinoblastoma tumors
      either as primary therapy or following external beam radiation. Currently,
      through the utilization of plaque radiation therapy, enucleation may be avoided
      in the majority of patients, and many patients may retrieve some visual acuity.
      We will review plaque brachytherapy techniques, diagnosis, staging, and some of
      the pertinent literature of the two most frequently encountered primary ocular
      tumors: choroidal melanoma, sometimes referred to as uveal melanoma, with an
      incidence of approximately 1,500 new cases per year in the adult population; and
      retinoblastoma, the most common intraocular primary malignancy found in
      childhood, with a frequency of approximately 250 [corrected] new cases per year.

PMID- 9143055
TI  - Applications of brachytherapy in head and neck cancer.
AB  - Brachytherapy offers the radiation oncologist the opportunity to deliver high
      doses of radiation to the tumor, with minimal doses to the surrounding normal
      tissue. This combination enhances the therapeutic ratio. It allows for enhanced
      tumor control, with minimal toxicity. When utilized, it often allows for tumor
      control without the need for resection. This is especially important in the head
      and neck. Resection of organs such as the lip, oral tongue, base-of-tongue, and
      other sites can cause significant functional and cosmetic morbidity. The ability
      to save these structures, using radiation therapy instead of surgery, can provide
      excellent tumor control and optimal quality-of-life outcome. In situations of
      recurrent disease, especially when prior radiation has been given, brachytherapy
      is often the only way to re-irradiate certain areas. This can be done alone, or
      in combination with surgery. Therefore, brachytherapy becomes an important
      component of the treatment of recurrent disease. This broad overview of the use
      of brachytherapy in head and neck cancer will include applications in the primary
      as well as the recurrent disease setting.

PMID- 9143056
TI  - Intracavitary brachytherapy for carcinoma of the esophagus.
AB  - Local control of unresectable esophageal carcinomas remains a significant problem
      in spite of aggressive treatments. External beam radiation therapy, chemotherapy,
      and combined modality treatment have all been employed with limited success. Here
      we review the existing literature and our own experience with external beam
      radiation followed by low-dose-rate or high-dose-rate intracavitary radiation for
      carcinoma of esophagus. The addition of intracavitary brachytherapy to external
      beam irradiation is well tolerated, causes no significant toxicity, and improves
      local control. Low-dose-rate intracavitary boost compared to high-dose-rate
      intracavitary boost has the advantage of a greater margin of safety, requires a
      single application, does not require highly sophisticated computerized
      technology, and is accompanied with fewer high-grade toxicities. Combined
      modality therapy consisting of concomitant infusional chemotherapy, external beam
      irradiation, and low-dose-rate intracavitary boost needs to be investigated.

PMID- 9143057
TI  - Brachytherapy and breast cancer.
AB  - Brachytherapy has been an important component of radiation therapy for breast
      cancer. It played a historical role in the development of breast-conserving
      techniques for early-stage breast cancer. The primary use for brachytherapy in
      this setting has been to deliver a localized boost dose of radiation to the
      lumpectomy bed after whole breast radiation therapy. In recent years, there has
      been less utilization of brachytherapy as a boost technique. This is
      predominantly related to wider availability of electrons for delivering a boost
      dose. Another significant factor for the decline is the controversy of whether
      routine boosting of the tumor bed is necessary for all early-stage breast cancer
      patients after conservative surgery and whole breast radiation therapy. Despite
      this, brachytherapy is still the preferred boost technique in certain subsets of
      patients. Newer applications of brachytherapy for the treatment of breast cancer
      have emerged and have shown promise. For early-stage breast cancer, these include
      brachytherapy as the sole radiation modality after lumpectomy and in combination
      with local excision as an alternative to mastectomy for treatment of local
      recurrences after conservative surgery and radiation therapy. In selected locally
      advanced cases of breast cancer, brachytherapy has been used as part of a
      technique that attempts breast conservation. At this time, these newer uses of
      brachytherapy for the treatment of breast cancer remain investigational.

PMID- 9143058
TI  - Role of brachytherapy in adult soft tissue sarcomas.
AB  - The use of brachytherapy in the management of adult soft tissue sarcomas of the
      extremities has been applied in combination with conservative surgery in an
      attempt to avoid amputation. Retrospective studies and a single prospective trial
      currently underway suggest that this combination is highly effective in improving
      local control for high-grade tumors, independent of size, location in the
      extremity, and depth. However, no effect has been shown in preventing distant
      metastases, or in prolonging survival in high-grade tumors. Likewise, no effect
      has been documented on low-grade tumors. Whether adjuvant chemotherapy can
      improve overall and disease-free survival remains debatable. New innovative
      brachytherapy approaches are being investigated to eliminate radiation exposure
      associated with the use of low-dose-rate Iridium-192 (Ir-192), and to further
      improve the treatment results in all tumor grades.

PMID- 9143059
TI  - Brachytherapy and pancreatic cancer.
AB  - Advances in diagnostic and therapeutic technology have not appreciably changed
      the outlook of patients with pancreatic cancer. While those patients presenting
      with localized resectable disease have the best prognosis, local control and
      intra-abdominal metastases remain significant obstacles to survival. Localized
      chemoradiation has modestly improved median survival in localized and locally
      advanced disease. Patients presenting with locally advanced disease at diagnosis
      benefit from surgical palliation which includes biliary and gastric bypass.
      Intraoperative interstitial brachytherapy has been effective when utilized at
      laparotomy to improve local control in locally advanced disease. Advances in
      laparoscopic techniques have provided the ability to more accurately stage
      patients prior to laparotomy and perform palliative procedures without the need
      for laparotomy. The utilization of high-dose-rate brachytherapy has proven
      effective in palliating obstructive symptoms with minimal morbidity on an
      outpatient basis. Recent efforts have focused on preoperative chemoradiation to
      improve resectability in selected patients and prophylactic hepatic irradiation
      to reduce metastases for patients with locally advanced disease.

PMID- 9143060
TI  - Brachytherapy for cancer of the female urethra.
AB  - Carcinoma of the female urethra is uncommon. The review of literature and our own
      experience indicates that early distal urethral cancers (squamous and
      adenocarcinoma) can be treated either with surgery (70-80% 5-year survival) or
      with radiotherapy (brachytherapy) with excellent results (75% 5-year survival).
      Early proximal or entire urethral cancers (squamous and adenocarcinoma), if
      treated surgically, will require exenterative procedures. Alternatively, these
      cancers can be treated with a combination of external beam and brachytherapy with
      or without chemotherapy with good results and preservation of organs. Surgery can
      be used for failures or persistent tumors. Advanced cancers require a
      multimodality approach, and a combination of radiation and chemotherapy appears
      to be the optimal way to treat these patients-with surgery to be used for biopsy
      proven persistent tumors or recurrences.

PMID- 9143061
TI  - Clinical experience with sonographic contrast agents.
AB  - Early generations of sonographic contrast agents are beginning to reach the
      attention of the clinician. Research and development of ultrasound contrast
      agents is progressing at a rapid pace with several new agents approaching US Food
      and Drug Administration approval. Cardiac imaging has been affected by even the
      limited availability of contrast agents on the market today both with regard to
      diagnosis of shunts and chamber opacification, and most recently actual
      enhancement of the myocardium. Later generations of contrast are capable of
      providing consistent opacification of both peripheral veins and arteries, and
      should prove useful in a variety clinical applications. Thus far, it appears that
      longer vessel segments may be seen with contrast rather than without contrast,
      and that flow may be demonstrated in vessels which were not seen or thought to be
      occluded with conventional color imaging. Improved detection of arterial and
      venous collaterals and enhanced identification of run-off vessels is demonstrated
      with sonographic contrast agents. An improved ability to evaluate renal artery
      stenosis and subtotal occlusion of the carotid artery are specific advantages of
      using contrast as well. Several compounds are currently being tested that may
      allow routine parenchymal opacification. Ultrasound is the most commonly
      performed diagnostic imaging procedure; therefore, contrast agents have the
      potential to dramatically alter the practice of clinical medicine. This article
      reviews the current status of ultrasound contrast agents and speculates regarding
      the future applications of these agents.

PMID- 9143062
TI  - Power Doppler: it's a good thing.
AB  - Power Doppler is a new method of ultrasound flow imaging the utility of which is
      currently under investigation. This technique creates a flow map based on the
      integrated power of the Doppler spectrum, rather than mean Doppler frequency.
      Power Doppler imaging is inherently more sensitive in terms of flow detection
      than standard color Doppler imaging; therefore, power Doppler can display flow
      for situations in which color Doppler is ineffective and can even display tissue
      perfusion in highly vascular organs such as the kidneys. Furthermore, power
      Doppler is not effected by aliasing, nor is it effected by blooming in the same
      way as color Doppler, which has deleterious effects on color Doppler flow images.
      The control of blooming with power Doppler may be of great importance in the
      clinical application of echo-enhancing agents. This review article discusses in
      detail the technological advantages and disadvantages of power Doppler flow
      imaging. In addition, it provides a synopsis of the preliminary research studies
      that have been conducted to date with respect to the clinical applications of
      power Doppler.

PMID- 9143063
TI  - Doppler ultrasound of the kidney.
AB  - Conventional ultrasound of the kidney is used commonly to depict structural
      abnormalities. It is limited, however, by a lack of functional and vascular
      information. Doppler sonography can reduce this limitation of standard sonography
      quickly and noninvasively. Doppler examinations, although not difficult, must be
      done property to obtain useful data. Information regarding the presence and
      direction of flow in renal vessels can be obtained. Vascular stenosis can be
      identified by several Doppler criteria, although the role of Doppler as a
      screening measure remains controversial. Assessment of vascular resistance is
      possible from Doppler waveform analysis, using parameters such as the resistive
      index. These data may provide hemodynamic and predictive information regarding a
      dilated collecting system identified by conventional ultrasound. Analysis of the
      resistive index also may provide helpful clinical information in nonobstructive
      renal disease. In certain clinical settings, such analysis provides diagnostic
      data not readily available with other clinical and laboratory assessment methods.
      Pharmacologically stimulated renal Doppler examinations may lead to even greater
      benefits in the future. This article reviews renal Doppler ultrasound, including
      the physiological basis for Doppler examination, the technical principles of
      renal Doppler sonography, and the clinical applications of Doppler findings.

PMID- 9143064
TI  - Controversies in venous ultrasound.
AB  - Ultrasound is the principal method used for diagnosing deep venous thrombosis in
      the United States, and its accuracy and limitations are well known. As venous
      ultrasound examination has matured, several controversial issues, primarily
      clinical, have arisen concerning the application of this diagnostic method. This
      article addresses some of the more noteworthy and vexing issues, including, but
      not limited to (a) the need to examine both legs in patients with unilateral
      symptoms; (b) the role of venous ultrasound in patients with bilateral leg
      swelling; (c) the necessary extent of the venous ultrasound examination; (d) the
      importance of calf vein thrombosis; (e) the significance of negative leg veins in
      a patient with possible pulmonary embolus; and (f) deep venous thrombosis in
      patients with occult malignancy. Technical aspects of the venous ultrasound
      examination, and diagnostic accuracy are not described.

PMID- 9143065
TI  - Duplex sonography of lower extremity arteries.
AB  - Although indirect noninvasive tests continue to play a role in the evaluation of
      patients with lower extremity arterial disease, the direct approach of duplex
      scanning provides both anatomic and physiological information directly from the
      involved arterial sites. Experience has shown that the results of duplex scanning
      are comparable with those of arteriography. The addition of color Doppler imaging
      to standard duplex scanning expedites the examination by helping to identify
      vessels and localize flow disturbances. However, precise classification of
      disease severity still requires spectral waveform analysis. Initial screening of
      patients with duplex scanning can determine the severity of arterial occlusive
      disease, the location of the lesions, and which interventional techniques are
      most appropriate. Arteriography can then be reserved for those patients who are
      being considered for therapeutic interventions. Duplex scanning has become the
      primary diagnostic test for follow-up of patients after radiological or surgical
      procedures and should be considered as an essential component of care for
      patients with infrainguinal bypass grafts. It has also proven to be valuable for
      intraoperative assessment and the initial evaluation of suspected vascular trauma
      in the extremities. Finally, new applications such as compression therapy for
      pseudoaneurysms continue to evolve and expand the role of duplex scanning in the
      management of patients with vascular problems.

PMID- 9143067
TI  - New Doppler parameters for carotid stenosis.
AB  - The recently published clinical trials of carotid endarterectomy marked a turning
      point in carotid sonography, because they provided justification for seeking
      carotid stenosis with ultrasound in both symptomatic and asymptomatic patients.
      These trials also were a turning point because they set a new standard for
      measuring carotid stenosis from arteriograms, based on the comparison of the
      least diameter of the residual internal carotid artery (ICA) lumen and the
      diameter of the normal, distal ICA. The adoption of this new standard for
      arteriographic measurement has necessitated the redefinition of velocity criteria
      for duplex Doppler diagnosis of ICA stenosis. This article discusses the methods
      for establishing Doppler velocity criteria for the identification of clinically
      significant carotid ICA stenosis, based on the new standard for arteriographic
      measurement.

PMID- 9143066
TI  - Evaluation and characterization of carotid plaque.
AB  - Doppler sonography, combining high-resolution imaging and Doppler spectrum
      analysis, has proven to be the best choice for safe, noninvasive, low-cost
      screening for the etiology of stroke. With high-resolution imaging, plaque can be
      characterized relative to the risk for intraplaque hemorrhage, thought by many to
      be the precursor of plaque ulceration. Using high-resolution ultrasound,
      heterogeneous plaque has been shown to be associated with intraplaque hemorrhage.
      Criteria for distinguishing heterogeneous from homogeneous plaque are discussed,
      as are techniques for characterizing plaque. Several published articles strongly
      suggest that, when heterogeneous plaques are identified, the incidence of
      neurological symptoms and stroke on follow-up increases, relative to patients
      with homogeneous plaques. Additional long-term follow-up studies of heterogeneous
      plaque are needed. Most recently, carotid wall thickness has been evaluated as a
      physiological marker for atherosclerotic disease and as a gauge of the
      effectiveness of medical therapies. It is likely that carotid wall thickness will
      become important in the diagnosis and management of atherosclerosis. Radiologist
      are encouraged to learn this new form of ultrasound examination, which is
      reviewed briefly in this article.

PMID- 9143068
TI  - A randomized controlled trial of the effect of exercise on sleep.
AB  - We tested the hypothesis that exercise would improve subjective sleep quality and
      activity in depressed elders. A 10-week randomized controlled trial was utilized.
      Participants consisted of a volunteer sample, aged > 60 with a diagnosis of major
      or minor depression or dysthymia. A total of 32 subjects aged 60-84 years with a
      mean age of 71.3 +/- 1.2 years was used. Intervention consisted of a supervised
      weight-training program three times a week or an attention-control group. Main
      outcome measures were Pittsburgh Subjective Sleep Quality Index (PSQI), Likert
      Scale of Subjective Sleep Quality and Quantity. Paffenbarger Activity Index.
      Geriatric Depression Scale (GDS). Beck Depression Inventory (BDI), Hamilton
      Rating Scale of Depression (HRSD), and the Medical Outcomes Survey Short Form 36
      (SF-36). Results showed that exercise significantly improved all subjective sleep
      quality and depression measures. Depression measures were reduced by
      approximately twice that of controls. Habitual activity was not significantly
      increased by exercise. Quality of life subscales significantly improved. In a
      forward stepwise multiple regression, percent improvement in GDS and percent
      increase in strength remained significant predictors of the improvement in total
      PSQI score (r = 0.71, p = 0.0002). In conclusion, weight lifting exercise was
      effective in improving subjective sleep quality, depression, strength, and
      quality of life without significantly changing habitual activity.

PMID- 9143069
TI  - Electrophysiological correlates of higher states of consciousness during sleep in
      long-term practitioners of the Transcendental Meditation program.
AB  - Standard ambulatory night sleep electroencephalograph (EEG) of 11 long-term
      practitioners of the Transcendental Meditation (TM) program reporting "higher
      states of consciousness" during sleep (the experimental group) was compared to
      that of nine short-term practitioners and 11 non-practitioners. EEG tracings
      during stages 3 and 4 sleep showed the experimental group to have: 1) theta-alpha
      activity simultaneously with delta activity and 2) decreased chin electromyograph
      (EMG) during deep sleep (p = 0.002) compared to short-term practitioners.
      Spectral analysis fast Fourier transform (FFT) data of the first three cycles
      showed that: 3) the experimental subjects had significantly greater theta 2 (6-8
      Hz)-alpha 1 (8-10 Hz) relative power during stages 3 and 4 than the combined
      control groups [t(30) = 5.5, p = 0.0000008] with no difference in time in delta;
      4) there was a graded difference across groups during stages 3 and 4 in theta 2
      alpha 1 power, with experimentals having greater power than short-term
      practitioners, who in turn had greater power than non-practitioners [t(30) =
      5.08, p = 0.00002]; and 5) experimentals also had increased rapid eye movement
      (REM) density during REM periods compared to short-term practitioners (p = 0.04).
      Previous studies have found increased theta-alpha EEG activity during reported
      periods of "transcendental consciousness" during the TM technique. In the Vedic
      tradition, as described by Maharishi Mahesh Yogi, transcendental consciousness is
      the first of a sequence of higher states. The maintenance of transcendental
      consciousness along with deep sleep is said to be a distinctive criterion of
      further, stabilized higher states of consciousness. The findings of this study
      are interpreted as physiological support for this model.

PMID- 9143070
TI  - A factor replication of the Sleep-Wake Activity Inventory (SWAI) in a Mexican
      population.
AB  - The purpose of this study was to describe the factor structure of the Sleep-Wake
      Activity Inventory (SWAI) in a Mexican population. In a sample of 722 Mexican
      college students, we replicated five of the six factors originally described in
      the SWAI. Retained factors included: excessive daytime sleepiness (similarity
      coefficient of 0.735), psychic distress (0.609), social desirability (0.638),
      individual's ability to relax (0.864), and nocturnal sleep (0.660). These results
      confirm the factor structure and extend the possible utility of the SWAI in a
      siesta culture.

PMID- 9143071
TI  - Decreased attentional responsivity during sleep deprivation: orienting response
      latency, amplitude, and habituation.
AB  - Ever increasing societal demands for uninterrupted work are causing unparalleled
      amounts of sleep deprivation among workers. Sleep deprivation has been linked to
      safety problems ranging from medical misdiagnosis to industrial and vehicular
      accidents. Microsleeps (very brief intrusions of sleep into wakefulness) are
      usually cited as the cause of the performance decrements during sleep
      deprivation. Changes in a more basic physiological phenomenon, attentional shift,
      were hypothesized to be additional factors in performance declines. The current
      study examined the effects of 36 hours of sleep deprivation on the electrodermal
      orienting response (OR), a measure of attentional shift or capture. Subjects were
      71 male undergraduate students, who were divided into sleep deprivation and
      control (non-sleep deprivation) groups. The expected negative effects of sleep
      deprivation on performance were noted in increased reaction times and increased
      variability in the sleep-deprived group on attention-demanding cognitive tasks.
      OR latency was found to be significantly delayed after sleep deprivation, OR
      amplitude was significantly decreased, and habituation of the OR was
      significantly faster during sleep deprivation. These findings indicate impaired
      attention, the first revealing slowed shift of attention to novel stimuli, the
      second indicating decreased attentional allocation to stimuli, and the third
      revealing more rapid loss of attention to repeated stimuli. These phenomena may
      be factors in the impaired cognitive performance seen during sleep deprivation.

PMID- 9143072
TI  - Sleep-promoting and hypothermic effects of daytime melatonin administration in
      humans.
AB  - Sleep-promoting and hypothermic effects of orally administered melatonin during
      the daytime were assessed using a placebo-controlled, double-blind, cross-over
      design. Following a 7-hour nighttime sleep opportunity, healthy young male
      subjects (n = 8) were given either a placebo or one of three doses of melatonin
      (1 mg, 10 mg, and 40 mg) at 1000 hours. Sleep was polygraphically assessed in a 4
      hour sleep opportunity from 1200 to 1600 hours. All doses of melatonin
      significantly shortened the latency to sleep onset. Melatonin also significantly
      increased total sleep time and decreased wake after sleep onset (WASO). Sleep
      following melatonin administration contained significantly more stage 2 and less
      stage 3-4, while stage 1 and rapid eye movement (REM) sleep were unaffected. In
      addition to the sleep-promoting effects, melatonin completely suppressed the
      normal diurnal rise of core body temperature. These data suggest that melatonin
      may be an effective method of promoting sleep for individuals attempting to sleep
      during their subjective day, such as shiftworkers and individuals rapidly
      traveling across multiple time zones.

PMID- 9143073
TI  - Computer classification of state in healthy preterm neonates.
AB  - Nineteen electroencephalographic (EEG) sleep measures describing four physiologic
      aspects of sleep behavior (i.e. sleep continuity, EEG spectra, body and eye
      movements, and autonomic measures) were derived from visual and computer analyses
      of 71 24-channel, 3-hour EEG sleep recordings on 52 healthy preterm neonates from
      28-36.5 weeks postconceptional age (PCA). Forty-eight subjects were
      neurodevelopmentally normal up to 2 years of age. Four electrographic states that
      comprise trace discontinu of the preterm neonate were defined in terms of
      increasing seconds of EEG quiescence per minute. A regression analysis was
      performed after transformations of nonlinear data sets representing the 19 EEG
      sleep measures, with the four sleep states as outcome variables. Postconceptional
      age was also included in these analyses as the 20th explanatory variable. Four
      measures best defined the EEG sleep states, explaining 75% of the variance:
      decreasing rapid eye movements per minute, decreasing numbers of spontaneous
      arousals per minute, increasing spectral theta energies, and decreasing facial
      movements per minute. Other cerebral and noncerebral measures, including total
      spectral EEG energies, spectral EEG energies in three bandwidths (i.e. delta,
      alpha, beta), cardiac and respiratory measures, and body movements, did not
      contribute as significantly to the prediction. Inclusion of PCA into the
      regression equation with the four EEG measures, selected by the analysis
      procedure, indicated that its contribution to state prediction was also small;
      the effect of PCA on state was found to be explained by the four EEG sleep
      measures.

PMID- 9143074
TI  - Maternal sleep and arousals during bedsharing with infants.
AB  - Contrary to popular perception, studies show that parent-infant bedsharing is not
      uncommon in American society. A belief that bedsharing with infants negatively
      impacts the quality of adult sleep also appears wide-spread. This has not been
      substantiated, however, because the few studies that have measured the impact of
      bedsharing on adult sleep examined only bedsharing with another adult. In the
      present study, laboratory polysomnography was performed in 20 routinely
      bedsharing and 15 routinely solitary-sleeping, breastfeeding, Latino mother
      infant pairs comparing the mothers' sleep when bedsharing to solitary-sleeping
      nights. Infants were 11-15 weeks old at the time. Irrespective of routine
      sleeping arrangement, mothers' total sleep time was not decreased on the
      bedsharing night compared to the solitary night. Across the two groups, percent
      Stage 3-4 sleep (of total sleep time) was significantly reduced on the bedsharing
      night but only by 3.9%, while Stage 1-2 sleep was increased 3.7%. Episodes of
      both Stages 3-4 and 1-2 were significantly shorter. The amount of rapid eye
      movement (REM) sleep was unaffected. Overall, arousal frequency was significantly
      increased by 3.6 hour-1. As the increase in arousal frequency was stage specific,
      it could account for the pattern of stage changes. Nocturnal wakefulness was not
      increased, however, because awakenings were of shorter duration. these effects of
      bedsharing did not habituate with routine bedsharing because they were not
      diminished in the routinely bedsharing mothers compared to the routinely solitary
      sleeping mothers. We find that the impact of bedsharing on maternal sleep is
      modest and somewhat different from the reported impact of sleeping with another
      adult. From the infant's standpoint, the effects on maternal sleep are adaptive
      to the extent that opportunities to monitor the infant's status are enhanced. The
      mother's caregiver role is likely germane to differential effects on sleep of
      bedsharing with an infant versus another adult.

PMID- 9143075
TI  - Heart rate variability in children with obstructive sleep apnea.
AB  - Adults with obstructive sleep apnea syndrome (OSAS) display substantial heart
      rate changes associated with obstructive events, and recent reports suggest
      similar heart rate changes in children with OSAS. These rate changes could assist
      screening of young patients for OSAS. Six-hour polysomnographic recordings were
      obtained from seven children with OSAS (mean age: 4.5 years; apnea index: 19.5 +/
      5.1) and from seven primary snorers without OSAS who served as controls (mean
      age: 4.7; apnea index: 0). Scatterplots of each cardiac R-R interval against the
      preceding interval (Poincare plots) were used to assess beat-to-beat cardiac
      variability at different heart rates. Beat-to-beat variation at slow rates was
      significantly increased in children with OSAS relative to controls, while
      variation at fast and intermediate heart rates was significantly reduced in these
      children. We conclude that OSAS alters beat-to-beat variation in characteristic
      fashions in children, that the variability changes occur at all heart rates but
      are most significant at slow heart rates, and that these heart rate patterns
      could assist in screening of suspected cases of OSAS.

PMID- 9143076
TI  - Long-term effects of a dental appliance therapy: a case of obstructive sleep
      apnea syndrome with enuresis.

PMID- 9143077
TI  - Neuropsychological function in mild sleep-disordered breathing.
AB  - Although a broad range of neuropsychological deficits has been reported in
      patients with severe sleep disordered breathing (SDB), little is known about the
      impact of mild SDB on neuropsychological performance. In this study, we compared
      neuropsychological test performance in two groups of carefully screened
      volunteers who differed clearly according to the respiratory disturbance index
      (RDI). Controls (n = 20) were identified on the basis of an RDI < 5; cases (n =
      32) had an RDI in the range of 10-30. Cases and controls were well matched with
      regard to IQ, age, and sex. Cases had significantly more self-reported snorting
      and apneas and a higher body mass index than controls but did not differ
      according to sleepiness as measured by either the multiple sleep latency test or
      the Epworth sleepiness scale. An extensive battery of neuropsychological and
      performance tests was administered after an overnight sleep study. Cases
      performed significantly more poorly on a visual vigilance task (perceptual
      sensitivity, d': 2.24 +/- 0.64 vs. 2.70 +/- 0.53, p = 0.01, for cases and
      controls, respectively) and a test of working memory, the Wechsler adult
      intelligence scale-revised digits backwards test (6.12 +/- 2.20 vs. 7.55 +/-
      2.22, p = 0.02), than controls. The groups did not differ in their performance on
      other tests of memory, information processing, and executive functioning. In
      summary, subjects with mild SDB may manifest a vigilance deficit in the absence
      of substantial sleepiness. Subjects with a mildly elevated RDI (10-30) without
      sleepiness do not appear to suffer appreciable deficits in more complex
      neuropsychological processes (e.g. executive functions).

PMID- 9143079
TI  - Bibliography of recent literature in sleep research.

PMID- 9143078
TI  - Assessment of respiratory effort by means of strain gauges and esophageal
      pressure swings: a comparative study.
AB  - We characterized apneas by a quantitative method (esophageal pressure
      measurements) and by a qualitative method (strain gauges) at the same time in 22
      patients with sleep-related breathing disorders. Detection of respiratory effort
      by strain gauges significantly overestimated the total number of central apneas
      in each patient. Despite this overestimation, none of the patients was wrongly
      diagnosed as having pure central sleep apnea syndrome. Strain gauges are
      sufficiently reliable for the characterization of apneas in most patients. When
      strain gauges reveal that most apneas are central in origin, verification by
      esophageal pressure measurements is recommended.

PMID- 9143080
TI  - Prevention of urinary tract infection in patients with spinal cord injury--a
      microbiological review.
AB  - The importance of urinary tract infection (UTI) in patients with spinal cord
      injury cannot be understated. Many patients with significant bacteriuria are
      considered to be colonised rather than infected, and treatment should be reserved
      for those with clinical symptoms or other signs of infection. Published research
      on the prevention and management of UTI in patients with spinal cord injury often
      has limitations due to differences in definitions of UTI, studies on groups using
      different urinary drainage appliances, the mixture of newly injured and
      longstanding injured patients and studies being carried out predominantly on male
      patients. The complications due to UTI and the difficulties in treating
      established infection mean that prevention is essential. Close urological follow
      up is crucial in ensuring that adequate bladder drainage is achieved avoiding the
      use of long term indwelling urinary catheters if at all possible. For those
      patients who require long term urinary appliances patient education and strict
      attention to hygiene and catheter care policies is important. The role of
      antiseptic/ antibiotics is strictly limited in preventing UTI in patients with
      spinal cord injury and may even be harmful. Further study into which groups of
      patients may benefit from the use of antiseptics or antibiotics is urgently
      required. Continued research into different methods of prevention eg by
      vaccination, immunotherapy, the use of receptor analogues and bladder
      interference should also be encouraged.

PMID- 9143081
TI  - Motor cortical mapping of proximal upper extremity muscles following spinal cord
      injury.
AB  - Focal transcranial magnetic stimulation was used to map the motor cortical
      representations of the relaxed and gently contracted biceps brachii, deltoid and
      triceps muscles in 22 subjects comprised of 12 controls, five subjects with
      complete and five with incomplete cervical spinal cord lesions (SCI). Motor
      evoked potentials (MEPs) were rarely observed during the resting condition (3/30
      muscles tested; SCI group) which precluded detailed analysis of these data. With
      background facilitation, the mean number of scalp stimulation sites producing
      MEPs varied according to muscle (P < 0.001); biceps yielded the largest maps and
      triceps the smallest. The cortical representations of proximal upper extremity
      muscles were largest for the control group and smallest for the incomplete SCI
      group although differences were not significant (P > 0.09). The optimal site of
      stimulation (that which produced the largest MEP) was always surrounded by an
      area producing submaximal MEPs, but was variable across subjects and groups.
      There was extensive overlap in the motor cortical representation areas
      corresponding to the three muscles of interest. Following maximal intensity
      stimulation at the optimal site, the mean MEP amplitudes (normalized) were
      largest for the biceps muscle and smallest or absent in triceps (P < 0.02). No
      differences were detected between groups (P > 0.50). The threshold stimulus
      intensity was highest for those with incomplete SCI and lowest amongst control
      subjects (P < 0.05), with biceps then deltoid muscles generally having lower
      thresholds than triceps (P < 0.001). The findings suggest that cortical map areas
      and MEP characteristics are not significantly altered in gently contracting
      muscles innervated by nerve roots rostral to the lesion. Only activation
      thresholds are higher following SCI, particularly incomplete lesions, although
      there is no apparent association with sensorimotor function. The inability to
      elicit MEPs in the relaxed muscles of patients with SCI fail to support previous
      reports of expanded motor cortical representations associated with muscles
      innervated by roots rostral to the lesion.

PMID- 9143082
TI  - Correlation between clinical neurological data and urodynamic function in spinal
      cord injured patients.
AB  - In 92 patients with spinal cord lesion, out of spinal shock, the data from a
      clinical neurological examination of the lumbosacral area are compared with the
      data from a full urodynamic investigation, including evaluation of sensation in
      the lower urinary tract. A significant correlation can be found between different
      levels of spinal cord lesion, the function of bladder neck and sphincter and the
      anal bulbocavernosus reflexes. Higher lesions correspond more with a reflexic
      lower urinary tract and somatic motor activity, lower lesions more with
      areflexia. With a lesion between thoracic 10 and lumbar 2 as many reflexic as
      areflexic lower urinary tract dysfunctions were found. The presence or absence of
      perineal sensation of light touch corresponded significantly with the presence or
      absence of sensation in the lower urinary tract. Detrusor and striated sphincter
      reflexia/areflexia corresponded significantly with the presence/absence of
      bulbocavernosus and anal reflexes. Clinical neurological examination gives useful
      information which acceptably corresponds with the LUT function. However to decide
      on a detailed individual diagnosis, clinical examination is in our opinion
      insufficient. Urodynamic tests are needed for a profound evaluation of the
      function of different parts of the lower urinary tract and their interaction.

PMID- 9143083
TI  - Assisted reach and transfers in individuals with tetraplegia: towards a solution.
AB  - The purpose of this study was to investigate the influence of a prototype trunk
      orthosis to assist an individual with tetraplegia. A single case study (26 year
      old male, C5 motor complete) using an interrupted time series analysis was
      conducted to investigate the individual's ability to reach, forward and
      laterally, and transfer with and without the orthosis. All tasks were performed
      on an AMTI force platform in the long sitting position, with landmarks of the
      trunk and limbs recorded using Peak Performances Technologies motion analysis
      system. After a familiarisation period ten trials were attempted for each phase
      of the analysis. With the orthosis the subject altered the sitting posture and
      significantly (F = 9.55, P = 0.003) increased the distance the subject was able
      to reach. The median frequency of the centre of pressure (COP) displacement
      during the reaching task was not significantly altered. The ability to displace
      the COP when attempting to transfer increased from 16.0 (+/-3.4 cm) to 19.6 (+/
      2.5 cm), however, this was not statistically significant. The likely user
      population, the overall functional benefits, the compliance of the users and
      possible modifications to the device to facilitate use with functional electrical
      stimulation are all possible directions for future research.

PMID- 9143084
TI  - Demineralization in tetraplegic and paraplegic man over time.
AB  - The aim of the present study was to compare bone mineral density (BMD in g/cm2)
      in the lumbar spine and three hip regions of male spinal cord injured subjects at
      various times post injury to age-matched able-bodied controls and to correlate
      their BMDs to their age and level of their spinal cord lesion. Patients and
      controls were stratified into three 20 years age groups (20-39, 40-59, and 60+
      years of age). BMD measurements were obtained using dual energy X-ray
      absorptiometry (DEXA, Lunar Model DPX). BMD levels taken within the first year of
      injury were not significantly lower than the age-matched able-bodies controls.
      The 20-39 year old patients injured longer than 1 year had significantly lower (P
      < or = 0.01) BMDs in their femoral region than both their age matched controls
      and the 20-39 year old acutely injured (injured for less than 1 year) patients.
      Although femoral BMDs of both paraplegic and quadriplegic patients 40-59 and 60+
      years of age decreased over time, none showed significant bone loss in this
      regions until 10 years after their injury. These results indicate that spinal
      cord injury associated bone loss occurs most dramatically in the femoral region
      of young men. These results also indicate that initial bone mass loss does not
      occur prior to 1 year post-injury to the extent that it is detectable by
      densitometry, or at least it did not occur in our patients.

PMID- 9143085
TI  - The importance of osmolality in hydrophilic urethral catheters: a crossover
      study.
AB  - The longterm use of clean intermittent self catheterisation as an option for
      bladder management in the care of spinal cord injury patients has shown the
      possible risk of urethral trauma and chronic infections being developed over
      time. The basic properties of the catheters being used need to be evaluated. In
      this crossover study of 14 male spinal cord injury patients, two commercial
      hydrophilic catheters were compared, as to the maximum friction force during the
      removal of the catheters after bladder emptying. The friction force, measured by
      a dynamometer twice daily, showed significant lower values for LoFric (0.87/0.84
      N) than for EsiCath/Conveen (1.38/1.27 N). Sticking to the urethral epithelium
      was reported three times (two patients) with the LoFric catheter, and 42 times
      (nine patients) with the EasiCath catheter. Osmolality of the outer layer of the
      catheters was measured using a freezing-point reduction technique. The greater
      than 10 times higher osmolality (approximately 900 mOsm/kg) of the Lofric
      catheter may explain the results.

PMID- 9143086
TI  - Muscle damage occurring in wheelchair sports people.
AB  - Seven college-age healthy men exercised on a wheelchair treadmill to evaluate
      muscle damage that may occur from wheelchair propulsion. An experimental model in
      which a participant performs up-hill running in a wheelchair was prepared. Plasma
      creatinekinase (CK), myoglobin (Mb) and lactatedehydrogenase (LDH) were measured
      as parameters. Blood samples were taken pre-, immediately after-, 24 h after- and
      72 h after the exercise. All of these parameters significantly increased after
      the exercise, but their time-courses were apparently varied. It is concluded that
      wheelchair propulsion causes muscle damage in certain situations such as up-hill
      running.

PMID- 9143087
TI  - Labour force participation and employment among a sample of Australian patients
      with a spinal cord injury.
AB  - This study examined the employment achievements of 219 spinal cord injured people
      and attempted to identify predictors which, individually and in combination, (a)
      discriminated between those who were in the labour force or not, and (b)
      correlated with the amount of time in employment post injury. Results indicated
      that at the time of the survey 26% were in full-time work, 11% were in part-time
      work, 4% were unemployed and 59% were not actively seeking work. Multivariate
      analyses identified three variables (impairment type, study since injury, level
      of pre-injury secondary schooling) which were related to both labour force
      participation and the amount of work undertaken post-injury. These results are
      discussed with reference to post-injury services that could be offered to spinal
      cord injury people who wish to return to work or gain employment.

PMID- 9143088
TI  - Obesity and spinal cord injury: an observational study.
AB  - Obesity as an independent factor influencing the eventual rehabilitation outcome
      of spinal cord injured individuals has not been examined. This paper is an
      observational study of two patients with complete tetraplegia secondary to spinal
      cord injury. Both patients encountered several problems specifically related to
      their obesity which with the rehabilitation process, and both were far below the
      expected functional outcome level for a C7 tetraplegic individual at the time of
      their discharge. Both patients were discharged to facilities providing the
      highest level of care available in the province.

PMID- 9143089
TI  - Correlation between K complex, periodic leg movements (PLM), and myoclonus during
      sleep in paraplegic adults before and after an acute physical activity.
AB  - K complex is the characteristic wave of stage II of sleep. The relationship
      between periodic limb movements (PLM) and the restless legs syndrome (RLS), and
      the incidence of K complexes and alpha activity has been previously described.
      The aim of the present study was to evaluate the effect of an acute physical
      activity upon K complex, PLM, and myoclonus during sleep in individuals who were
      paraplegic. We evaluated 84 polysomnograms from 28 volunteers with a spinal cord
      injury at the level of T7-T12, obtained during three consecutive nights. On day
      3, the volunteers were submitted to a test of maximum effort (manual
      cycloergometer, with the equipment Cybex Met 300, with a progressive load
      increase of 12.5 w, every 2 min). The analysis of the polysomnographic recordings
      showed a positive correlation between the incidence of K complex and limb
      movements on nights 1, 2 and 3. Similarly, a correlation between the incidence of
      K complex and myoclonus was observed on nights 1, 2 and 3. An increased incidence
      of the total K complex was seen on night 3, 36 h after the test maximum effort.
      Both total K complex and K complex/h were reduced on night 2, compared to basal
      recording (night 1). There was a reduction of sleep latency on night 2, whereas
      total sleeping time increased progressively on night 3, as well as REM phase on
      nights 2 and 3. These findings indicate that physical activity can effect or
      modulate the incidence of K complex and suggest that a positive correlation
      between PLM and K complex may occur in those who are paraplegic from a spinal
      cord injury. In conclusion, sleep can be consolidated after physical activity.

PMID- 9143090
TI  - Traumatic spinal cord injuries in Jordan--an epidemiological study.
AB  - To survey the situation of traumatic spinal cord injuries (SCI) in Jordan and for
      a future nationwide epidemiological survey, a retrospective study was conducted
      at the Royal Jordanian Rehabilitation Centre (RJRC) King Hussein Medical Centre
      (KHMC) Amman-Jordan, where all traumatic cases within this centre in addition to
      a few nontraumatic spinal injury patients are referred to the spinal unit which
      has a capacity of 30 beds. 151 traumatic SCI patients who were admitted to the
      spinal unit at RJRC during the period January 1988 to December 1993 were
      reviewed. The estimated annual incidence was 18 per million population. The
      majority were predominantly males (85.4%) the male/female ratio was 5.8:1. The
      mean age at the time of injury was 33 being 30.9 years for males and 34.8 years
      for females. There were 68% (n = 103) with paraplegia and 32% (n = 48) with
      tetraplegia (Frankel A-D). The commonest aetiology was motor vehicle accidents
      (44.4% n = 67), next came bullet injuries (25.8% n = 39), followed by accidental
      falls (21.2% n = 32). Other causes of SCI, and also the importance of preventive
      measures are discussed.

PMID- 9143091
TI  - Autonomic hyperreflexia associated with recurrent cardiac arrest: case report.
AB  - Autonomic hyperreflexia is a condition which may occur in individuals with spinal
      cord injuries above the splanchnic sympathetic outflow. Noxious stimuli can
      produce profound alterations in sympathetic pilomotor, sudomotor, and vasomotor
      activity, as well as disturbances in cardiac rhythm. A case of autonomic
      hyperreflexia in a patient with C6 tetraplegia with recurrent ventricular
      fibrillation and cardiac arrest illustrates the profound effects of massive
      paroxysmal sympathetic activity associated with this condition.

PMID- 9143092
TI  - Effects of finasteride, a type 2 5-alpha reductase inhibitor, on fetal
      development in the rhesus monkey (Macaca mulatta).
AB  - In genetic male fetuses, dihydrotestosterone (DHT) plays an important role in
      normal prostatic and external genital differentiation. The enzyme steroid 5-alpha
      reductase (5 alpha R) catalyzes the conversion of testosterone (T) to DHT. The
      importance of 5 alpha R in sexual differentiation is evident from the study of
      human genetic males who congenitally lack this enzyme and consequently develop
      ambiguous genitalia. These individuals are specifically deficient in the type 2
      isozyme, whereas the normal type 1 isozyme activity has been found. The purpose
      of this study was to determine 1) the suitability of the rhesus monkey for
      testing the safety of 5 alpha R inhibitors when administered during pregnancy and
      2) the potential risk of administering a known type 2 5 alpha R inhibitor,
      finasteride, during the critical period of internal and external genital
      differentiation in rhesus monkeys. In vitro studies were also performed on
      selected rhesus monkey tissues to determine the distribution of the 5 alpha R
      isozymes. Gravid monkeys were treated once daily from gestational days (GD) 20 to
      100. Sonographic monitoring was performed during the course of gestation to
      monitor viability, growth, and organ system development. Detailed fetal
      evaluations for developmental abnormalities were performed at term (GD 152 +/-
      2). A group of 13 pregnant monkeys ("positive control") were given a high oral
      dose (2 mg/kg/day) of finasteride to demonstrate that inhibiting type 2 5 alpha R
      results in specific external genital abnormalities in male fetuses. Thirty-two
      pregnant monkeys were administered an intravenous (i.v.) formulation of
      finasteride at doses of 8, 80, or 800 ng/day. The highest i.v. dose selected was
      at least 60-750 times the semen levels of finasteride in man given orally 5 or 1
      mg/day, respectively. Seventeen vehicle-control pregnant monkeys were also
      included. Administration of a high oral dose (2 mg/kg/day) of finasteride
      resulted in external genital abnormalities characterized by hypospadias,
      preputial adhesions to the glans, a small underdeveloped scrotum, a small penis,
      and a prominent midline raphe in male fetuses; however, no developmental
      abnormalities were seen in female fetuses. Similarly, no abnormalities were
      observed in either male or female fetuses of mothers given iv doses (8, 80, or
      800 ng/day) of finasteride during pregnancy. The in utero sonographic findings in
      fetuses correlated with the gross findings at term. These studies have shown that
      external genital abnormalities can be produced in male monkey fetuses when
      exposed to a high oral dose (2 mg/kg/day) of finasteride, whereas no
      abnormalities were observed in fetuses exposed to the i.v. formulation of
      finasteride. Detailed in vitro studies demonstrated that the rhesus monkey also
      has two 5 alpha R isozymes (types 1 and 2) with a tissue distribution similar to
      that seen in man and, furthermore, that finasteride is a potent, mechanism-based
      inhibitor with selectivity for both human and rhesus type 2 5 alpha R. These
      studies have demonstrated that the monkey is a suitable model for assessing the
      safety of 5 alpha R inhibitors administered during pregnancy.

PMID- 9143093
TI  - Periconceptional intake of vitamin A among women and risk of neural tube defect
      affected pregnancies.

PMID- 9143094
TI  - Comparison of national policies on periconceptional use of folic acid to prevent
      spina bifida and anencephaly (SBA).

PMID- 9143095
TI  - Methanol causes posteriorization of cervical vertebrae in mice.
AB  - Inhalation of methanol by pregnant mice before gestation day nine (gd 9) produces
      fetal skeletal alterations, principally in the cervical region. The appearance of
      these defects suggests homeotic shifts in segment identity, patterning, or both.
      To explore this possibility, detailed morphological analyses of the effects of
      methanol on fetal skeletal development were done. Pregnant mice were gavaged with
      0, 4.0, or 5.0 g/kg methanol (MeOH) split in two doses on gd 7, the most
      sensitive day for induction of skeletal alterations with methanol. Dams were
      killed on gd 18 and the fetuses were counted, weighed, and examined externally.
      Fetuses were double stained with alcian blue and alizarin red for examination of
      cartilaginous and ossified vertebral and rib characteristics, and in selected
      fetuses cervical vertebrae were disarticulated for more detailed analysis.
      Observations indicative of methanol-induced homeotic transformations were as
      follows: [tabular data: see abstract volume] Examination of disarticulated
      vertebrae revealed foramina and other distinguishing characteristics on vertebrae
      anterior to those on which they normally appear. These results demonstrate that
      maternal methanol exposure can alter segment patterning in the developing mouse
      embryo, producing posteriorization of cervical vertebrae.

PMID- 9143096
TI  - Teratogen update: toluene.
AB  - Extrapolating from animal data, at the level at which well-controlled
      occupational exposure to toluene vapor is encountered, in utero exposure does not
      pose a significant fetal risk. However, following chronic and excessive
      industrial accidents or intentional abuse, toluene exposure several orders of
      magnitude greater exists, and at these levels in utero exposures in both animals
      and humans have been shown to produce significant delays in fetal growth. At
      these greater exposure levels, both dose and gestational timing relationships can
      be demonstrated in animal models. Of note, in both animals and humans, postnatal
      persistence of growth deficiency has been observed. A pattern of teratogenicity
      similar to that of the fetal alcohol syndrome is prevalent in all human studies
      of excessive in utero exposure to toluene. In humans, the effects of in utero
      toluene exposure among intentional abusers is confounded by such variables as
      general health and exposure to other teratogens. Chronic toluene abuse produces a
      renal tubular acidosis with maternal hypokalemia and profoundly lowered serum pH.
      Further evaluation of greater numbers of infants with respect to maternal renal
      tubular acidosis will be needed to fully assess the contribution of chronic
      acidosis. The contribution of maternal acidosis to fetal teratogenicity remains
      speculative. Coabuse of additional agents, in particular alcohol, may increase
      the teratogenic risks. The overlap of features following in utero toluene abuse
      with those of fetal alcohol syndrome suggests a possible common pathway of
      craniofacial teratogenesis. Lastly, genetic variations that result in deficiency
      of ALDH2, an enzyme involved in toluene metabolism, may increase the risks of
      toluene teratogenicity in at-risk individuals at lower levels of exposure.
      Prospective studies of toluene-exposed pregnancies would provide more information
      on the fetal effects at these levels.

PMID- 9143097
TI  - Immunomagnetic detection of Bacillus stearothermophilus spores in food and
      environmental samples.
AB  - There are currently no methods for the rapid and sensitive detection of bacterial
      spores that could be used to direct raw materials containing high spore loads
      away from products that pose a food safety risk. Existing methods require an
      overnight incubation, cannot detect spores below 10(5) CFU/ml, or are not
      specific to particular species. This work describes a method to specifically
      detect < 10(4) CFU of bacterial spores per ml within 2 h. Polyclonal antibodies
      to Bacillus stearothermophilus spores were attached to 2.8-micron-diameter
      magnetic polystyrene beads by using a polythreonine cross-linker via the antibody
      carbohydrate moiety. A biotin-avidin-amplified sandwich enzyme-linked
      immunosorbent assay coupled to a fluorescent substrate was used to quantitate
      captured spores. The concentration of B. stearothermophilus spores in samples was
      linearly correlated to fluorescent activity (r2 = 0.99) with a lower detection
      limit of 8 x 10(3) CFU/ml and an upper detection limit of 8 x 10(5) CFU/ml. The
      detection limits are not fixed and can be changed by varying the immunomagnetic
      bead concentration. Several food and environmental samples were tested to
      demonstrate the versatility of the assay.

PMID- 9143098
TI  - Use of a single procedure for selective enrichment, isolation, and identification
      of plasmid-bearing virulent Yersinia enterocolitica of various serotypes from
      pork samples.
AB  - Many selective enrichment methods for the isolation of Yersinia enterocolitica
      from foods have been described. However, no single isolation procedure has been
      described for the recovery and identification of various plasmid-bearing
      serotypes. A single improved procedure for selective enrichment, isolation,
      identification, and maintenance of plasmid-bearing virulent serotypes of Y.
      enterocolitica from pork samples was developed. Enrichment at 12 degrees C in
      Trypticase soy broth containing yeast extract, bile salts, and Irgasan was found
      to be an efficient medium for the recovery of plasmid-bearing virulent strains of
      Y. enterocolitica representing O:3; O:8; O:TACOMA; O:5, O:27; and O:13 serotypes.
      MacConkey agar proved to be a reliable medium for the isolation of presumptive
      colonies, which were subsequently confirmed as plasmid-bearing virulent strains
      by Congo red binding and low calcium response. Further confirmation by multiplex
      PCR employed primers directed at the chromosomal ail and plasmid-borne virF
      genes, which are present only in pathogenic strains. The method was applied to
      pig slaughterhouse samples and was effective in isolating plasmid-bearing
      virulent strains of Y. enterocolitica from naturally contaminated porcine
      tongues. Strains isolated from ground pork and tongue expressed plasmid
      associated phenotypes and mouse pathogenicity.

PMID- 9143099
TI  - ord1, an oxidoreductase gene responsible for conversion of O
      methylsterigmatocystin to aflatoxin in Aspergillus flavus.
AB  - Among the enzymatic steps in the aflatoxin biosynthetic pathway, the conversion
      of O-methylsterigmatocystin to aflatoxin has been proposed to be catalyzed by an
      oxidoreductase. Transformants of Aspergillus flavus 649WAF2 containing a 3.3-kb
      genomic DNA fragment and the aflatoxin biosynthesis regulatory gene aflR
      converted exogenously supplied O-methylsterigmatocystin to aflatoxin B1. A gene,
      ord1, corresponding to a transcript of about 2 kb was identified within the 3.3
      kb DNA fragment. The promoter region presented a putative AFLR binding site and a
      TATA sequence. The nucleotide sequence of the gene revealed an open reading frame
      encoding a protein of 528 amino acids with a deduced molecular mass of 60.2 kDa.
      The gene contained six introns and seven exons. Heterologous expression of the
      ord1 open reading frame under the transcriptional control of the Saccharomyces
      cerevisiae galactose-inducible gal1 promoter results in the ability to convert O
      methylsterigmatocystin to aflatoxin B1. The data indicate that ord1 is sufficient
      to accomplish the last step of the aflatoxin biosynthetic pathway. A search of
      various databases for similarity indicated that ord1 encodes a cytochrome P-450
      type monooxygenase, and the gene has been assigned to a new P-450 gene family
      named CYP64.

PMID- 9143100
TI  - Deletions in the carboxyl-terminal region of Streptococcus gordonii
      glucosyltransferase affect cell-associated enzyme activity and sucrose-associated
      accumulation of growing cells.
AB  - The single glucosyltransferase (GTF) of Streptococcus gordonii Challis CH1 makes
      alpha 1,3- and alpha 1,6-linked glucans from sucrose. The GTF carboxyl-terminal
      region has six direct repeats thought to be involved in glucan binding. Strains
      with defined mutations in this region have been described recently (M. M.
      Vickerman, M. C. Sulavik, P. E. Minick, and D. B. Clewell, Infect. Immun. 64:5117
      5128, 1996). Strain CH107 GTF has three internal direct repeats deleted; the 59
      carboxyl-terminal amino acids are identical to those of the parental strain. This
      deletion resulted in decreased enzyme activity but did not affect the amount of
      cell-associated GTF protein. The GTFs of strains CH2RPE and CH4RPE have six and
      eight direct repeats, respectively, but are both missing the 14 carboxyl-terminal
      amino acids. Strain CH2RPE had significantly decreased levels of cell-associated
      GTF; this decrease was not obviated by the increased number of direct repeats in
      strain CH4RPE. Thus, the carboxyl-terminal amino acids appeared to influence the
      amount of cell-associated GTF more than the direct repeats. The qualitative and
      quantitative differences in the GTFs did not affect the abilities of these
      strains to accumulate on hydroxyapatite beads in the absence of sucrose. However,
      when sucrose was added as a substrate for GTF, the mutant strains were unable to
      accumulate on these surfaces to the same extent as the parent. These differences
      in sucrose-associated accumulation may be due to changes in the nature of the
      glucans produced by the different enzymes and/or cohesive interactions between
      these glucans and the GTF on the surfaces of the growing streptococci.

PMID- 9143101
TI  - Comparison of ribotyping and randomly amplified polymorphic DNA PCR for
      characterization of Vibrio vulnificus.
AB  - A total of 85 isolates of Vibrio vulnificus were characterized by ribotyping with
      a probe complementary to 16S and 23S rRNA of Escherichia coli and by randomly
      amplified polymorphic DNA-PCR (RAPD-PCR) with a 10-mer oligonucleotide primer.
      The RAPD-PCR results were scanned, and the images were analyzed with a computer
      program. Ribotype membranes were evaluated visually. Both the ribotyping and the
      RAPD-PCR results showed that the collection of strains was genetically very
      heterogeneous. Ribotyping enabled us to differentiate U.S. and Danish strains and
      V. vulnificus biotypes 1 and 2, while the RAPD-PCR technique was not able to
      correlate isolates with sources or to differentiate the two biotypes, suggesting
      that ribotyping is useful for typing V. vulnificus strains whereas RAPD-PCR
      profiles may subdivide ribotypes. Two Danish clinical biotype 2 strains isolated
      from fishermen who contracted the infection cleaning eels belonged to the same
      ribotype as three eel strains (biotype 2), providing further evidence that V.
      vulnificus biotype 2 is an opportunistic pathogen for humans. One isolate
      (biotype 2) from Danish coastal waters also showed the same ribotype as the eel
      strains. This is, to our knowledge, the first time the isolation of V. vulnificus
      biotype 2 from coastal waters has been described.

PMID- 9143102
TI  - Effect of Bacillus thuringiensis toxins on the membrane potential of lepidopteran
      insect midgut cells.
AB  - To test whether the ability of Bacillus thuringiensis toxins to form pores in the
      midgut epithelial cell membrane of susceptible insects correlates with their in
      vivo toxicity, we measured the effects of different toxins on the electrical
      potential of the apical membrane of freshly isolated midguts from gypsy moth
      (Lymantria dispar) and silkworm (Bombyx mori) larvae. In the absence of toxin,
      the membrane potential, measured with a conventional glass microelectrode, was
      stable for up to 30 min. It was sensitive to the K+ concentration and the
      oxygenation of the external medium. Addition of toxins to which L. dispar is
      highly [CryIA(a) and CryIA(b)] or only slightly [CryIA(c) and CryIC] sensitive
      caused a rapid, irreversible, and dose-dependent depolarization of the membrane.
      CryIF, whose toxicity towards L. dispar is unknown, and CryIE, which is at best
      poorly active in vivo, were also active in vitro. In contrast, CryIB and CryIIIA,
      a coleopteran-specific toxin, had no significant effect. The basolateral-membrane
      potential was unaffected by CryIA(a) or CryIC when the toxin was applied to the
      basal side of the epithelium. In B. mori midguts, the apical-membrane potential
      was abolished by CryIA(a), to which silkworm larvae are susceptible, but CryIA(b)
      and CryIA(c); to which they are resistant, had no detectable effect. Although the
      technique discriminated between active and inactive toxins, the concentration
      required to produce a given effect varied much less extensively than the
      sensitivity of gypsy moth larvae, suggesting that additional factors influence
      the toxins' level of toxicity in vivo.

PMID- 9143103
TI  - Manipulation of independent synthesis and degradation of polyphosphate in
      Escherichia coli for investigation of phosphate secretion from the cell.
AB  - The genes involved in polyphosphate metabolism in Escherichia coli were cloned
      behind different inducible promoters on separate plasmids. The gene coding for
      polyphosphate kinase (PPK), the enzyme responsible for polyphosphate synthesis,
      was placed behind the Ptac promoter. Polyphosphatase, a polyphosphate
      depolymerase, was similarly expressed by using the arabinose-inducible PBAD
      promoter. The ability of cells containing these constructs to produce active
      enzymes only when induced was confirmed by polyphosphate extraction, enzyme
      assays, and RNA analysis. The inducer concentrations giving optimal expression of
      each enzyme were determined. Experiments were performed in which ppk was induced
      early in growth, overproducing PPK and allowing large amounts of polyphosphate to
      accumulate (80 mumol in phosphate monomer units per g of dry cell weight). The
      ppx gene was subsequently induced, and polyphosphate was degraded to inorganic
      phosphate. Approximately half of this polyphosphate was depleted in 210 min. The
      phosphate released from polyphosphate allowed the growth of phosphate-starved
      cells and was secreted into the medium, leading to a down-regulation of the
      phosphate-starvation response. In addition, the steady-state polyphosphate level
      was precisely controlled by manipulating the degree of ppx induction. The
      polyphosphate content varied from 98 to 12 mumol in phosphate monomer units per g
      of dry cell weight as the arabinose concentration was increased from 0 to 0.02%
      by weight.

PMID- 9143104
TI  - Gene cloning, purification, and characterization of a heat-stable phytase from
      the fungus Aspergillus fumigatus.
AB  - The finding of heat-stable enzymes or the engineering of moderately thermostable
      enzymes into more stable ones by random or site-directed mutagenesis has become a
      main priority of modern biotechnology. We report here for the first time a heat
      stable phytase able to withstand temperatures up to 100 degrees C over a period
      of 20 min, with a loss of only 10% of the initial enzymatic activity. The gene
      (phyA) encoding this heat-stable enzyme has been cloned from Aspergillus
      fumigatus and overexpressed in Aspergillus niger. The enzyme showed high activity
      with 4-nitrophenyl phosphate at a pH range of 3 to 5 and with phytic acid at a pH
      range of 2.5 to 7.5.

PMID- 9143106
TI  - Biodegradation of glyceryl trinitrate by Penicillium corylophilum Dierckx.
AB  - Penicillium corylophilum Dierckx, isolated from a contaminated water wet, double
      base propellant, was able to completely degrade glyceryl trinitrate (GTN) in a
      buffered medium (pH 7.0) containing glucose and ammonium nitrate. In the presence
      of 12 mg of initial fungal inoculum, GTN (48.5 to 61.6 mumol) was quantitatively
      transformed in a stepwise process to glyceryl dinitrate (GDN) and glyceryl
      mononitrate (GMN) within 48 h followed by a decrease in the GDN content with a
      concomitant increase in the GMN level. GDN was totally transformed to GMN within
      168 h, and the complete degradation of GMN was achieved within 336 h. The
      presence of glucose and ammonium nitrate in the growth medium was essential for
      completion of the degradation of GTN and its metabolites. Complete degradation of
      GTN by a fungal culture has not been previously reported in the literature.

PMID- 9143105
TI  - Sequence analysis and characterization of pOM1, a small cryptic plasmid from
      Butyrivibrio fibrisolvens, and its use in construction of a new family of cloning
      vectors for Butyrivibrios.
AB  - As a preliminary step in the development of vector systems, we have isolated and
      begun to characterize small, cryptic plasmids from several strains of the rumen
      bacterium Butyrivibrio fibrisolvens. We present here the complete nucleotide
      sequence of Butyrivibrio plasmid pOM1, which was isolated from B. fibrisolvens
      Bu49. While it is very similar in size to the previously characterized
      Butyrivibrio plasmids pRJF1 and pRJF2, pOM1 exhibits a restriction pattern which
      is quite distinct. Analysis of sequence data reveals that pOM1 contains only two
      open reading frames of significant length (ORF1 and ORF2), both of which are
      required for self-replication and maintenance. The protein encoded in ORF1 shows
      homologies with Pre (plasmid recombination enzyme) proteins encoded in plasmids
      from gram-positive organisms such as Staphylococcus aureus, Streptococcus
      agalactiae, Lactobacillus plantarum, and Bacillus thuringiensis. The putative
      translation product of ORF2, on the other hand, resembles Rep (replication)
      proteins of a different group of gram-positive plasmids, for which the
      Staphylococcus plasmid pSN2 is a prototype. Unlike the other characterized
      Butyrivibrio plasmids, pOM1 appears to replicate via a rolling-circle mechanism.
      Experimental evidence showing the presence of a single-stranded replication
      intermediate consistent with this mechanism is presented. pOM1 has been used in
      the construction of a new Escherichia coli-B. fibrisolvens shuttle vector,
      pSMerm1, which has been successfully used to introduce a cloned gene into B.
      fibrisolvens harboring the pRJF1 plasmid.

PMID- 9143107
TI  - Purification and properties of methyl formate synthase, a mitochondrial alcohol
      dehydrogenase, participating in formaldehyde oxidation in methylotrophic yeasts.
AB  - Methyl formate synthase, which catalyzes methyl formate formation during the
      growth of methylotrophic yeasts, was purified to homogeneity from methanol-grown
      Candida boidinii and Pichia methanolica cells. Both purified enzymes were
      tetrameric, with identical subunits with molecular masses of 42 to 45 kDa,
      containing two atoms of zinc per subunit. The enzymes catalyze NAD(+)-linked
      dehydrogenation of the hydroxyl group of the hemiacetal adduct [CH2(OH)OCH3] of
      methanol and formaldehyde, leading to the formation of a stoichiometric amount of
      methyl formate. Although neither methanol nor formaldehyde alone acted as a
      substrate for the enzymes, they showed simple NAD(+)-linked alcohol dehydrogenase
      activity toward aliphatic long-chain alcohols such as octanol, showing that they
      belong to the class III alcohol dehydrogenase family. The methyl formate synthase
      activity of C. boidinii was found in the mitochondrial fraction in subcellular
      fractionation experiments, suggesting that methyl formate synthase is a homolog
      of Saccharomyces cerevisiae Adh3p. These results indicate that formaldehyde could
      be oxidized in a glutathione-independent manner by methyl formate synthase in
      methylotrophic yeasts. The significance of methyl formate synthase in both
      formaldehyde resistance and energy metabolism is also discussed.

PMID- 9143108
TI  - Subcuticular bacteria from the brittle star Ophiactis balli (Echinodermata:
      Ophiuroidea) represent a new lineage of extracellular marine symbionts in the
      alpha subdivision of the class Proteobacteria.
AB  - Many species of echinoderms, in all five extant classes, contain subcuticular
      bacterial symbionts (SCB). The role of these extracellular symbionts and the
      nature of the relationship remain unclear. We have sequenced 16S rRNA genes from
      symbionts to determine their phylogenetic affinities. Symbionts of an ophiuroid,
      Ophiactis balli, appear closely related to bacteria within the alpha group of the
      class Proteobacteria, including intracellular endosymbionts and pathogens. SCB
      are clearly of separate origin from other documented major groups of marine
      symbiotic bacteria.

PMID- 9143109
TI  - Cell surface characteristics of Lactobacillus casei subsp. casei, Lactobacillus
      paracasei subsp. paracasei, and Lactobacillus rhamnosus strains.
AB  - Hydrophilic and electrostatic cell surface properties of eight Lactobacillus
      strains were characterized by using the microbial adhesion to solvents method and
      microelectrophoresis, respectively. All strains appeared relatively hydrophilic.
      The strong microbial adhesion to chloroform, an acidic solvent, in comparison
      with microbial adhesion to hexadecane, an apolar n-alkane, demonstrated the
      particularity of lactobacilli to have an important electron donor and basic
      character and consequently their potential ability to generate Lewis acid-base
      interactions with a support. Regardless of their electrophoretic mobility (EM),
      strains were in general slightly negatively charged at alkaline pH. A pH
      dependent behavior concerning cell surface charges was observed. The EM decreased
      progressively with more acidic pHs for the L. casei subsp. casei and L. paracasei
      subsp. paracasei strains until the isoelectric point (IEP), i.e., the pH value
      for which the EM is zero. On the other hand, the EM for the L. rhamnosus strains
      was stable from pH 8 to pH 3 to 4, at which point there was a shift near the IEP.
      Both L. casei subsp. casei and L. paracasei subsp. paracasei strains were
      characterized by an IEP of around 4, whereas L. rhamnosus strains possessed a
      markedly lower IEP of 2. The present study showed that the cell surface
      physicochemical properties of lactobacilli seem to be, at least in part and under
      certain experimental conditions, particular to the bacterial species. Such
      differences detected between species are likely to be accompanied by some
      particular changes in cell wall chemical composition.

PMID- 9143111
TI  - Cyclosporin C is the main antifungal compound produced by Acremonium luzulae.
AB  - A strain of Acremonium luzulae (Fuckel) W. Gams was selected in screening new
      microorganisms for biological control of fruit postharvest diseases, especially
      gray and blue mold diseases on apples and strawberries. This strain manifests a
      very strong activity against a large number of phytopathogenic fungi. In this
      work, the product responsible for this antifungal activity was isolated from
      modified Sabouraud dextrose broth cultures of A. luzulae. It was purified to
      homogeneity by reverse-phase column chromatography. On the basis of UV, infrared,
      and 1H and 13C nuclear magnetic resonance spectra, mass spectral analysis, and
      the amino acid composition of the acid hydrolysates, the antibiotic was
      determined to be cyclosporin C. Cyclosporin C showed a broad-spectrum activity
      against filamentous phytopathogenic fungi but no activity against bacteria or
      yeasts. Its antifungal activity is only fungistatic. In contrast to Tolypocladium
      inflatum, another cyclosporin-producing strain, A. luzulae, did not produce
      additional cyclosporins. This was confirmed by in vivo-directed biosynthesis.

PMID- 9143110
TI  - Isolation and characterization of two new homoacetogenic hydrogen-utilizing
      bacteria from the human intestinal tract that are closely related to Clostridium
      coccoides.
AB  - Two gram-positive, strictly anoxic, coccoid- to rod-shaped strains of bacteria,
      Clostridium coccoides 1410 and C. coccoides 3110, were isolated from human feces
      on the typical homoacetogenic substrates formate plus H2 plus CO2 (strain 1410)
      and vanillate plus H2 plus CO2 (strain 3110) in the presence of 2
      bromoethanesulfonate to inhibit methanogenesis. On the basis of 16S rRNA
      sequencing, DNA-DNA hybridization, and physiological and morphological
      parameters, both isolates are closely related to C. coccoides DSM 935T. The G+C
      contents of the DNA were 46.1 and 46.2 mol% for C. coccoides 1410 and C.
      coccoides 3110, respectively. Cytochromes could not be detected. Formate was
      degraded exclusively to acetate, whereas vanillate was O-demethylated, resulting
      in acetate and 3,4-dihydroxybenzoate, the latter being further decarboxylated to
      catechol. In the presence of organic substrates, H2 was cometabolized to acetate,
      but both strains failed to grow autotrophically. Lactose, lactulose, sorbitol,
      glucose, and various other carbohydrates supported growth as well. Untypical of
      homoacetogens, glucose and sorbitol were fermented not exclusively to acetate;
      instead, considerable amounts of succinate and D-lactate were produced. H2 was
      evolved from carbohydrates only in negligible traces. Acetogenesis from formate
      plus H2 plus CO2 or vanillate plus H2 plus CO2 was constitutive, whereas
      utilization of carbohydrates was inducible. Hydrogenase, CO dehydrogenase,
      formate dehydrogenase, and all of the tetrahydrofolic acid-dependent, C1 compound
      converting enzymes of the acetyl-coenzyme A pathway of homoacetogenesis were
      present in cell extracts.

PMID- 9143112
TI  - Cloning, nucleotide sequence, and regulatory analysis of the Nitrosomonas
      europaea dnaK gene.
AB  - The dnaK gene of an ammonia-oxidizing bacterium, Nitrosomonas europaea, was
      cloned and sequenced. It was found that the dnaK gene product was highly
      homologous to previously analyzed dnaK gene products from other organisms at the
      amino acid level. Two partial open reading frames located upstream and downstream
      of the dnaK gene were also found and identified as grpE and dnaJ genes,
      respectively, by the predicted amino acid homology of their gene products to
      other bacterial GrpE and DnaJ proteins. Transcription of the dnaK gene was
      strongly induced by a heat shock from 30 to 37 degrees C. An analysis of the
      expression of the dnaK gene fused to the lacZ translational reporter gene also
      showed eightfold increase in beta-galactosidase activity after the heat shock
      induction. Heat-inducible transcription start sites of the dnaK gene, revealed by
      primer extension analysis, were located 16 and 17 nucleotides upstream from the
      translational start codon of the dnaK gene, and the predicted promoter sequence
      showed a homology to the consensus sequence of sigma 32-dependent heat shock
      promoters of gram-negative bacteria. The upstream region of the dnaK gene did not
      contain the inverted repeat structure that was involved in the regulation of the
      heat shock gene of several gram-negative and gram-positive bacteria. Therefore,
      we conclude that the heat shock regulatory mechanism of the N. europaea dnaK gene
      may be similar to the sigma 32-dependent mechanism observed in other gram
      negative bacteria.

PMID- 9143113
TI  - Molecular epidemiological survey of rotaviruses in sewage by reverse
      transcriptase seminested PCR and restriction fragment length polymorphism assay.
AB  - Rotavirus double-stranded RNA was detected directly in sewage treatment plant
      samples over a 1-year period by reverse transcription followed by PCR
      amplification of the VP7 gene and Southern blot hybridization. The presence of
      naturally occurring rotaviruses was demonstrated in 42% of raw sewage samples and
      in 67% of treated effluent samples. Amplified viral sequences were analyzed by
      restriction enzymes. Ten different restriction profiles were characterized, most
      of which were found in treated effluent samples. A mixture of restriction
      profiles was observed in 75% of contaminated effluent samples. The profiles were
      compared with those obtained from human rotavirus isolates involved in infections
      in children from the same area (six different profiles were detected). Five
      identical viral sequences were detected in both environmental and clinical
      samples. Restriction profiles were also compared to profiles from known genomic
      sequences of human and animal viruses. Both human and animal origins of rotavirus
      contamination of water seemed likely.

PMID- 9143115
TI  - Induction of heat shock proteins DnaK, GroEL, and GroES by salt stress in
      Lactococcus lactis.
AB  - The bacterium Lactococcus lactis has become a model organism in studies of growth
      physiology and membrane transport, as a result of its simple fermentative
      metabolism. It is also used as a model for studying the importance of specific
      genes and functions during life in excess nutrients, by comparison of
      prototrophic wild-type strains and auxotrophic domesticated (dairy) strains. In a
      study of the capacity of domesticated strains to perform directed responses
      toward various stress conditions, we have analyzed the heat and salt stress
      response in the established L. lactis subsp. cremoris laboratory strain MG1363,
      which was originally derived from a dairy strain. After two-dimensional
      separation of proteins, the DnaK, GroEL, and GroES heat shock proteins, the HrcA
      (Orf1) heat shock repressor, and the glycolytic enzymes pyruvate kinase, glyceral
      dehyde-3-phosphate dehydrogenase, and phosphoglycerate kinase were identified by
      a combination of Western blotting and direct N-terminal amino acid sequencing of
      proteins from the gels. Of 400 to 500 visible proteins, 17 were induced more than
      twofold during heat stress. Two classes of heat stress proteins were identified
      from their temporal induction pattern. The fast-induced proteins (including DnaK)
      showed an abruptly increased rate of synthesis during the first 10 min, declining
      to intermediate levels after 15 min. GroEL and GroES, which also belong to this
      group, maintained a high rate of synthesis after 15 min. The class of slowly
      induced proteins exhibited a gradual increase in the rate of synthesis after the
      onset of stress. Unlike other organisms, all salt stress-induced proteins in L.
      lactis were also subjected to heat stress induction. DnaK, GroEL, and GroES
      showed similar temporal patterns of induction during salt stress, resembling the
      timing during heat stress although at a lower induction level. These data
      indicate an overlap between the heat shock and salt stress responses in L.
      lactis.

PMID- 9143114
TI  - Evaluation of a novel subtilisin inhibitor gene and mutant derivatives for the
      expression and secretion of mouse tumor necrosis factor alpha by Streptomyces
      lividans.
AB  - In order to evaluate the expression and secretion signals of the highly secreted
      subtilisin inhibitor of Streptomyces venezuelae CBS762.70 (VSI) for the
      production of heterologous proteins by Streptomyces lividans, mouse tumor
      necrosis factor alpha (mTNF) was chosen as a model protein. The mTNF cDNA was
      fused to the vsi signal sequence. The analysis of secretion by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and biological activity measurements
      revealed an efficient translocation of mTNF. Up to 300 mg of secreted
      biologically active mTNF per liter could be obtained in shaken-flask cultures. By
      analyzing the effects of mutations in the N region of the VSI signal peptide on
      secretion, we found that decreasing the +3 charge of the wild-type protein to +2
      resulted in a 3- to 10-fold increase in secretion.

PMID- 9143116
TI  - Clustering of trichothecene-producing Fusarium strains determined from 28S
      ribosomal DNA sequences.
AB  - The genus Fusarium includes several species that produce trichothecenes. We
      analyzed DNA sequences from a variable region at the 5' end of the large nuclear
      ribosomal DNA (rDNA) (28S) to determine the genetic relatedness of trichothecene
      producing Fusarium species. All trichothecene-producing strains clustered
      together, and two monophyletic groups were resolved. The first clade included
      strains of F. acuminatum, F. sambucinum, F. tumidum, F. compactum, F. camptoceras
      (red pigment), F. sporotrichioides, and F. venenatum, which produced type A
      trichothecenes (T-2 toxin, HT-2 toxin, neosolaniol, and diacetoxyscirpenol). The
      second clade consisted of strains of F. crookwellense, F. culmorum, and F.
      graminearum, which produced type B trichothecenes (fusarenone-X, nivalenol, and
      deoxynivalenol). The phylogenetic placement of the species based on rDNA
      correlated better with toxic secondary metabolite data rather than with the
      current classification system based on morphology.

PMID- 9143117
TI  - Glucose transport by mixed ruminal bacteria from a cow.
AB  - The glucose transport of mixed ruminal bacteria harvested from a holstein cow fed
      5.0 kg of Italian ryegrass and 1.5 kg of flaked corn a day was investigated. The
      Eadie-Hofstee plot characterized two transport systems: a high-affinity, low
      velocity system and a low-affinity, high-velocity system. The former system (K(m)
      = 16 microM; Vmax = 2.2 nmol/min/mg of protein) is considered dominant under this
      feeding condition based on the glucose concentration in the rumen (< 1 mM). In
      light of the facts that the protonophore SF6847 and the lipophilic
      triphenylmethyl phosphonium ion had no effect on the high-affinity system and an
      artificially generated proton gradient and electrical potential across the cell
      membrane did not increase glucose transport, a proton motive force is not be
      involved in the system. On the other hand, from the facts that chlorhexidine
      inhibited about 90% of the high-affinity system while iodoacetate showed no
      significant effect, and a high phosphoenolpyruvate-dependent phosphorylation of
      glucose was actually shown, the phosphoenolpyruvate-dependent phosphotransferase
      system is considered the main system in the high-affinity system. Moreover, as
      shown by the facts that harmaline inhibited about 30% of the high-affinity system
      and the artificially generated sodium gradient across the cell membrane
      significantly stimulated glucose transport, this system also includes sodium
      symport to some degree. The high-affinity system was sensitive to a decrease in
      pH (< 6.5) and was inhibited by the presence of sucrose, mannose, and fructose.

PMID- 9143118
TI  - Preparation of GM1 ganglioside with sialidase-producing marine bacteria as a
      microbial biocatalyst.
AB  - This paper describes the preparation of monosialoganglioside GM1 with sialidase
      producing marine bacteria as a microbial biocatalyst. A new sialidase-producing
      bacterium, identified tentatively as Pseudomonas sp. strain YF-2, was isolated
      from seawater by enrichment culture with ganglioside as the sole source of
      carbon. When YF-2 was cultured in a synthetic medium containing crude bovine
      brain gangliosides at 25 degrees C for 3 days, 80 to 90% of the gangliosides were
      converted to GM1. GM1 was then purified from the supernatant of YF-2 culture by
      C18 reverse-phased chromatography, followed by DEAE-Sephadex A25 anion-exchange
      chromatography. In a typical experiment, 178 mg of highly purified GM1 was
      obtained from 500 mg of the crude ganglioside fraction. The GM1 induced neurite
      outgrowth of neuroblastoma Neuro2a cells at a concentration of 33 to 100 microM
      in the presence of fetal calf serum. Sialidase was purified 33-fold with 13.3%
      recovery from the culture supernatant of YF-2. The purified enzyme hydrolyzed
      polysialogangliosides to produce GM1 but did not act on GM1. It was therefore
      concluded that polysialogangliosides in the culture of strain YF-2 were converted
      to GM1 by this sialidase.

PMID- 9143119
TI  - In vivo levels of chlorinated hydroquinones in a pentachlorophenol-degrading
      bacterium.
AB  - Sphingomonas chlorophenolica RA-2 is a soil microorganism that can grow on
      pentachlorophenol (PCP) as a sole carbon source. In this microorganism, PCP is
      converted to tetrachlorohydroquinone (TCHQ), trichlorohydroquinone, and 2,6
      dichlorohydroquinone. The remainder of the pathway has not yet been defined. The
      ability to grow on PCP as a sole carbon source is remarkable because of the
      toxicity of PCP and its chlorinated hydroquinone metabolites. Experiments in
      which the levels of PCP and chlorinated hydroquinones were measured in cells
      metabolizing [U-14C]PCP revealed that the levels of chlorinated hydroquinones in
      the cytoplasm are in the low micromolar range. The toxicity of chlorinated
      hydroquinones was evaluated by exposure of Escherichia coli cells that had been
      treated with EDTA (to remove the outer membrane) to TCHQ. Significant toxicity
      due to TCHQ was not apparent until concentrations of 500 microM and higher. Thus,
      an important part of the explanation for why S. chlorophenolica RA-2 is able to
      grow on PCP as a sole carbon source is undoubtedly that it can process sufficient
      carbon for growth without accumulating high levels of toxic intermediates.

PMID- 9143120
TI  - Characterization of an NaCl-sensitive Staphylococcus aureus mutant and rescue of
      the NaCl-sensitive phenotype by glycine betaine but not by other compatible
      solutes.
AB  - To further study mechanisms of coping with osmotic stress-low water activity,
      mutants of Staphylococcus aureus with transposon Tn917-lacZ-induced NaCl
      sensitivity were selected for impaired ability to grow on solid defined medium
      containing 2 M NaCl. Southern hybridization experiments showed that NaCl
      sensitive mutants had a single copy of the transposon inserted into a DNA
      fragment of the same size in each mutant. These NaCl-sensitive mutants had an
      extremely long lag phase (60 to 70 h) in defined medium containing 2.5 M NaCl.
      The osmoprotectants glycine betaine and choline (which is oxidized to glycine
      betaine) dramatically shortened the lag phase, whereas L-proline and proline
      betaine, which are effective osmoprotectants for the wild type, were ineffective.
      Electron microscopic observations of the NaCl-sensitive mutant under NaCl stress
      conditions revealed large, pseudomulticellular cells similar to those observed
      previously in the wild type under the same conditions. Glycine betaine, but not L
      proline, corrected the morphological abnormalities. Studies of the uptake of L
      [14C]proline and [14C]glycine betaine upon osmotic upshock revealed that the
      mutant was not defective in the uptake of either osmoprotectant. Comparison of
      pool K+, amino acid, and glycine betaine levels under NaCl stress conditions in
      the mutant and the wild type revealed no striking differences. Glycine betaine
      appears to have additional beneficial effects on NaCl-stressed cells beyond those
      of other osmoprotectants. The NaCl stress protein responses of the wild type and
      the NaCl-sensitive mutant were characterized and compared by labeling with L-[35
      S]methionine and two-dimensional gel electrophoresis. The synthesis of 10
      proteins increased in the wild type in response to NaCl stress, whereas the
      synthesis of these 10 proteins plus 2 others increased in response to NaCl stress
      in the NaCl-sensitive mutant. Five proteins, three of which were NaCl stress
      proteins, were produced in elevated amounts in the NaCl-sensitive mutant under
      unstressed conditions compared to the wild type. The presence of glycine betaine
      during NaCl stress decreased the production of three NaCl stress proteins in the
      mutant versus one in the wild type.

PMID- 9143122
TI  - Thiocarbamate herbicide-inducible nonheme haloperoxidase of Rhodococcus
      erythropolis NI86/21.
AB  - During biodegradation of thiocarbamate herbicides by Rhodococcus erythropolis
      NI86/21, a protein with an M(r) of 30,000 is induced (I. Nagy, G. Schoofs, F.
      Compernolle, P. Proost, J. Vanderleyden, and R.De Mot, J. Bacteriol. 177:676-687,
      1995). Based on N-terminal sequence data for the protein purified by two
      dimensional electrophoresis, the corresponding structural gene, thcF, was cloned
      and sequenced. The deduced protein sequence of ThcF is homologous to those of
      nonheme haloperoxidases. A particularly high level of sequence identity (72.6%)
      was observed for the chloroperoxidase from Pseudomonas pyrrocinia. A polyclonal
      antibody against the latter enzyme cross-reacted with ThcF either produced by the
      original Rhodococcus cells or overexpressed heterologously in Escherichia coli.
      In both thiocarbamate-grown Rhodococcus cells and E. coli cells expressing thcF,
      the haloperoxidase activity of ThcF was demonstrated. The thiocarbamate-inducible
      R. erythropolis ThcF protein represents the first (nonheme) haloperoxidase to be
      identified in a nocardioform actinomycete.

PMID- 9143121
TI  - The soluble methane monooxygenase gene cluster of the trichloroethylene-degrading
      methanotroph Methylocystis sp. strain M.
AB  - In methanotrophic bacteria, methane is oxidized to methanol by the enzyme methane
      monooxygenase (MMO). The soluble MMO enzyme complex from Methylocystis sp. strain
      M also oxidizes a wide range of aliphatic and aromatic compounds, including
      trichloroethylene. In this study, heterologous DNA probes from the type II
      methanotroph Methylosinus trichosporium OB3b were used to isolate souble MMO
      (sMMO) genes from the type II methanotroph Methylocystis sp. strain M. sMMO genes
      from strain M are clustered on the chromosome and show a high degree of identity
      with the corresponding genes from Methylosinus trichosporium OB3b. Sequencing and
      phylogenetic analysis of the 16S rRNA gene from Methylocystis sp. strain M have
      confirmed that it is most closely related to the type II methanotroph
      Methylocystis parvus OBBP, which, unlike Methylocystis sp. strain M, does not
      possess an sMMO. A similar phylogenetic analysis using the pmoA gene, which
      encodes the 27-kDa polypeptide of the particulate MMO, also places Methylocystis
      sp. strain M firmly in the genus Methylocystis. This is the first report of
      isolation and characterization of methane oxidation genes from methanotrophs of
      the genus Methylocystis.

PMID- 9143123
TI  - Combining the hok/sok, parDE, and pnd postsegregational killer loci to enhance
      plasmid stability.
AB  - To enhance plasmid segregational stability in bacterial cells, two pairs of
      independent postsegregational killing loci (genes which induce host killing upon
      plasmid loss) isolated from plasmids R1, R483, or RP4 (hok+/sok+ pnd+ or
      hok+/sok+ parDE+) were cloned into a common site of the beta-galactosidase
      expression vector pMJR1750 (ptac::lacZ+) to form a series of plasmids in which
      the effect of one or two stability loci on segregational plasmid stability could
      be discerned. Adding two antisense killer loci (hok+/sok+ pnd+) decreased the
      specific growth rate by 50% though they were more effective at reducing
      segregational instability than hok+/sok+ alone. With the ptac promoter induced
      fully (2.0 mM isopropyl-beta-D-thiogalactopyranoside) and no antibiotic selection
      pressure, the combination of a proteic killer locus (parDE+) with antisense
      killer loci (hok+/sok+) had a negligible impact on specific growth rate,
      maintained high beta-galactosidase expression, and led to a 30 and 190% increase
      in segregational stability (based on stable generations) as compared to plasmids
      containing either hok+/sok+ or parDE+ alone, respectively. Use of hok+/sok+ or
      parDE+ alone with high cloned-gene expression led to ninefold and fourfold
      increases in the number of stable generations, respectively. Two convenient
      cloning cassettes have been constructed to facilitate cloning the dual hok+/sok+
      parDE+ and hok+/sok+ pnd+ killer systems.

PMID- 9143124
TI  - Plant compounds that induce polychlorinated biphenyl biodegradation by
      Arthrobacter sp. strain B1B.
AB  - Plant compounds that induced Arthrobacter sp. strain B1B to cometabolize
      polychlorinated biphenyls (PCBs) were identified by a screening assay based on
      the formation of a 4,4'-dichlorobiphenyl ring fission product. A chemical
      component of spearmint (Mentha spicata), l-carvone, induced Arthrobacter sp.
      strain B1B to cometabolize Aroclor 1242, resulting in significant degradation of
      26 peaks in the mixture, including selected tetra- and pentachlorobiphenyls.
      Evidence for PCB biodegradation included peak disappearance, formation of a
      phenylhexdienoate ring fission product, and chlorobenzoate accumulation in the
      culture supernatant. Carvone was not utilized as a growth substrate and was toxic
      at concentrations of greater than 500 mg liter-1. Several compounds structurally
      related to l-carvone, including limonene, p-cymene, and isoprene, also induced
      cometabolism of PCBs by Arthrobacter sp. strain B1B. A structure-activity
      analysis showed that chemicals with an unsaturated p-menthane structural motif
      promoted the strongest cometabolism activity. These data suggest that certain
      plant-derived terpenoids may be useful for promoting enhanced rates of PCB
      biodegradation by soil bacteria.

PMID- 9143125
TI  - Molecular characterization of an inducible p-coumaric acid decarboxylase from
      Lactobacillus plantarum: gene cloning, transcriptional analysis, overexpression
      in Escherichia coli, purification, and characterization.
AB  - By using degenerate primers designed from the first 19 N-terminal amino acids of
      Lactobacillus plantarum p-coumaric acid decarboxylase (PDC), a 56-bp fragment was
      amplified from L. plantarum in PCRs and used as a probe for screening an L.
      plantarum genomic bank. Of the 2,880 clones in the genomic bank, one was isolated
      by colony hybridization and contained a 519-bp open reading frame (pdc gene)
      followed by a putative terminator structure. The pdc gene is expressed on a
      monocistronic transcriptional unit, which is transcribed from promoter sequences
      homologous to Lactococcus promoter sequences. No mRNA from pdc and no PDC
      activity were detected in uninduced cell extracts, indicating that the expression
      is transcriptionally regulated by p-coumaric acid, which corresponds to an
      activation factor up to 6,000. The pdc gene was overexpressed constitutively in
      Escherichia coli, and the recombinant enzyme was purified and characterized.

PMID- 9143126
TI  - Natural transformation and availability of transforming DNA to Acinetobacter
      calcoaceticus in soil microcosms.
AB  - A small microcosm, based on optimized in vitro transformation conditions, was
      used to study the ecological factors affecting the transformation of
      Acinetobacter calcoaceticus BD413 in soil. The transforming DNA used was A.
      calcoaceticus homologous chromosomal DNA with an inserted gene cassette
      containing a kanamycin resistance gene, nptII. The effects of soil type (silt
      loam or loamy sand), bacterial cell density, time of residence of A.
      calcoaceticus or of DNA in soil before transformation, transformation period, and
      nutrient input were investigated. There were clear inhibitory effects of the soil
      matrix on transformation and DNA availability. A. calcoaceticus cells reached
      stationary phase and lost the ability to be transformed shortly after
      introduction into sterile soil. The use of an initially small number of A.
      calcoaceticus cells and nutrients, resulting in bacterial growth, enhanced
      transformation frequencies within a limited period. The availability of
      introduced DNA for transformation of A. calcoaceticus cells disappeared within a
      few hours in soil. Differences in transformation frequencies between soils were
      found; A. calcoaceticus cells were transformed at a higher rate and for a longer
      period in a silt loam than in a loamy sand. Physical separation of DNA and A.
      calcoaceticus cells had a negative effect on transformation. Transformation was
      also detected in nonsterile soil microcosms, albeit only in the presence of added
      nutrients and at a reduced frequency. These results suggest that chromosomal DNA
      released into soil rapidly becomes unavailable for transformation of A.
      calcoaceticus. In addition, strain BD413 quickly loses the ability to receive,
      stabilize, and/or express exogenous DNA after introduction into soil.

PMID- 9143127
TI  - Effects of nisin and temperature on survival, growth, and enterotoxin production
      characteristics of psychrotrophic Bacillus cereus in beef gravy.
AB  - The presence of psychrotrophic enterotoxigenic Bacillus cereus in ready-to-serve
      meats and meat products that have not been subjected to sterilization treatment
      is a public health concern. A study was undertaken to determine the survival,
      growth, and diarrheal enterotoxin production characteristics of four strains of
      psychrotrophic B. cereus in brain heart infusion (BHI) broth and beef gravy as
      affected by temperature and supplementation with nisin. A portion of unheated
      vegetative cells from 24-h BHI broth cultures was sensitive to nisin as evidenced
      by an inability to form colonies on BHI agar containing 10 micrograms of
      nisin/ml. Heat-stressed cells exhibited increased sensitivity to nisin. At
      concentrations as low as 1 microgram/ml, nisin was lethal to B. cereus, the
      effect being more pronounced in BHI broth than in beef gravy. The inhibitory
      effect of nisin (1 microgram/ml) was greater on vegetative cells than on spores
      inoculated into beef gravy and was more pronounced at 8 degrees C than at 15
      degrees C. Nisin, at a concentration of 5 or 50 micrograms/ml, inhibited growth
      in gravy inoculated with vegetative cells and stored at 8 or 15 degrees C,
      respectively, for 14 days. Growth of vegetative cells and spores of B. cereus
      after an initial period of inhibition is attributed to loss of activity of nisin.
      One of two test strains produced diarrheal enterotoxin in gravy stored at 8 or 15
      degrees C within 9 or 3 days, respectively. Enterotoxin production was inhibited
      in gravy supplemented with 1 microgram of nisin/ml and stored at 8 degrees C for
      14 days; 5 micrograms of nisin/ml was required for inhibition at 15 degrees C.
      Enterotoxin was not detected in gravy in which less than 5.85 log10 CFU of B.
      cereus/ml had grown. Results indicate that as little as 1 microgram of nisin/ml
      may be effective in inhibiting or retarding growth of and diarrheal enterotoxin
      production by vegetative cells and spores of psychrotrophic B. cereus in beef
      gravy at 8 degrees C, a temperature exceeding that recommended for storage or for
      most unpasteurized, ready-to-serve meat products.

PMID- 9143128
TI  - Influence of cosubstrate concentration on xylose conversion by recombinant, XYL1
      expressing Saccharomyces cerevisiae: a comparison of different sugars and ethanol
      as cosubstrates.
AB  - Conversion of xylose to xylitol by recombinant Saccharomyces cerevisiae
      expressing the XYL1 gene, encoding xylose reductase, was investigated by using
      different cosubstrates as generators of reduced cofactors. The effect of a pulse
      addition of the cosubstrate on xylose conversion in cosubstrate-limited fed-batch
      cultivation was studied. Glucose, mannose, and fructose, which are transported
      with high affinity by the same transport system as is xylose, inhibited xylose
      conversion by 99, 77, and 78%, respectively, reflecting competitive inhibition of
      xylose transport. Pulse addition of maltose, which is transported by a specific
      transport system, did not inhibit xylose conversion. Pulse addition of galactose,
      which is also transported by a specific transporter, inhibited xylose conversion
      by 51%, in accordance with noncompetitive inhibition between the galactose and
      glucose/ xylose transport systems. Pulse addition of ethanol inhibited xylose
      conversion by 15%, explained by inhibition of xylose transport through
      interference with the hydrophobic regions of the cell membrane. The xylitol
      yields on the different cosubstrates varied widely. Galactose gave the highest
      xylitol yield, 5.6 times higher than that for glucose. The difference in redox
      metabolism of glucose and galactose was suggested to enhance the availability of
      reduced cofactors for xylose reduction with galactose. The differences in xylitol
      yield observed between some of the other sugars may also reflect differences in
      redox metabolism. With all cosubstrates, the xylitol yield was higher under
      cosubstrate limitation than with cosubstrate excess.

PMID- 9143129
TI  - Stimulation of aryl metabolite production in the basidiomycete Bjerkandera sp.
      strain BOS55 with biosynthetic precursors and lignin degradation products.
AB  - Aryl metabolites are known to have an important role in the ligninolytic system
      of white rot fungi. The addition of known precursors and aromatic acids
      representing lignin degradation products stimulated the production of aryl
      metabolites (veratryl alcohol, veratraldehyde, p-anisaldehyde, and 3-chloro-p
      anisaldehyde) in the white rot fungus Bjerkandera sp. strain BOS55. The presence
      of manganese (Mn) is known to inhibit the biosynthesis of veratryl alcohol (T.
      Mester, E. de Jong, and J.A. Field, Appl. Environ. Microbiol. 61:1881-1887,
      1995). A new finding of this study was that the production of the other aryl
      metabolites, p-anisaldehyde and 3-chloro-p-anisaldehyde, was also inhibited by
      Mn. We attempted to bypass the Mn-inhibited step in the biosynthesis of aryl
      metabolites by the addition of known and suspected precursors. Most of these
      compounds were not able to bypass the inhibiting effect of Mn. Only the fully
      methylated precursors (veratrate, p-anisate, and 3-chloro-p-anisate) provided
      similar concentrations of aryl metabolites in the presence and absence of Mn,
      indicating that Mn does not influence the reduction of the benzylic acid group.
      The addition of deuterated benzoate and 4-hydroxybenzoate resulted in the
      formation of deuterated aryl metabolites, indicating that these aromatic acids
      entered into the biosynthetic pathway and were common intermediates to all aryl
      metabolites. Only deuterated chlorinated anisyl metabolites were produced when
      the cultures were supplemented with deuterated 3-chloro-4-hydroxybenzoate. This
      observation combined with the fact that 3-chloro-4-hydroxybenzoate is a natural
      product of Bjerkandera spp. (H. J. Swarts, F. J. M. Verhagen, J. A. Field, and J.
      B. P. A. Wijnberg, Phytochemistry 42:1699-1701, 1996) suggest that it is a
      possible intermediate in chlorinated anisyl metabolite biosynthesis.

PMID- 9143130
TI  - An improved enzyme-linked immunosorbent assay for whole-cell determination of
      methanogens in samples from anaerobic reactors.
AB  - An enzyme-linked immunosorbent assay was developed for the detection of whole
      cells of methanogens in samples from anaerobic continuously stirred tank
      digesters treating slurries of solid waste. The assay was found to allow for
      quantitative analysis of the most important groups of methanogens in samples from
      anaerobic digesters in a reproducible manner. Polyclonal antisera against eight
      strains of methanogens were employed in the test. The specificities of the
      antisera were increased by adsorption with cross-reacting cells. The
      reproducibility of the assay depended on the use of high-quality microtiter
      plates and the addition of dilute hydrochloric acid to the samples. In an
      experiment on different digester samples, the test demonstrated a unique pattern
      of different methanogenic strains present in each sample. The limited preparatory
      work required for the assay and the simple assay design make the test well suited
      for routine analysis of large numbers of samples and thus for process
      surveillance during operation of biogas digesters.

PMID- 9143131
TI  - Taurine reduction in anaerobic respiration of Bilophila wadsworthia RZATAU.
AB  - Organosulfonates are important natural and man-made compounds, but until recently
      (T. J. Lie, T. Pitta, E. R. Leadbetter, W. Godchaux III, and J. R. Leadbetter.
      Arch. Microbiol. 166:204-210, 1996), they were not believed to be dissimilated
      under anoxic conditions. We also chose to test whether alkane- and
      arenesulfonates could serve as electron sinks in respiratory metabolism. We
      generated 60 anoxic enrichment cultures in mineral salts medium which included
      several potential electron donors and a single organic sulfonate as an electron
      sink, and we used material from anaerobic digestors in communal sewage works as
      inocula. None of the four aromatic sulfonates, the three unsubstituted
      alkanesulfonates, or the N-sulfonate tested gave positive enrichment cultures
      requiring both the electron donor and electron sink for growth. Nine cultures
      utilizing the natural products taurine, cysteate, or isethionate were considered
      positive for growth, and all formed sulfide. Two clearly different pure cultures
      were examined. Putative Desulfovibrio sp. strain RZACYSA, with lactate as the
      electron donor, utilized sulfate, aminomethanesulfonate, taurine, isethionate,
      and cysteate, converting the latter to ammonia, acetate, and sulfide. Strain
      RZATAU was identified by 16S rDNA analysis as Bilophila wadsworthia. In the
      presence of, e.g., formate as the electron donor, it utilized, e.g., cysteate and
      isethionate and converted taurine quantitatively to cell material and products
      identified as ammonia, acetate, and sulfide. Sulfite and thiosulfate, but not
      sulfate, were utilized as electron sinks, as was nitrate, when lactate was
      provided as the electron donor and carbon source. A growth requirement for 1,4
      naphthoquinone indicates a menaquinone electron carrier, and the presence of
      cytochrome c supports the presence of an electron transport chain. Pyruvate
      dependent disappearance of taurine from cell extracts, as well as formation of
      alanine and release of ammonia and acetate, was detected. We suspected that
      sulfite is an intermediate, and we detected desulfoviridin (sulfite reductase).
      We thus believe that sulfonate reduction is one aspect of a respiratory system
      transferring electrons from, e.g., formate to sulfite reductase via an electron
      transport system which presumably generates a proton gradient across the cell
      membrane.

PMID- 9143132
TI  - An assay combining cell culture with reverse transcriptase PCR to detect and
      determine the infectivity of waterborne Cryptosporidium parvum.
AB  - The presence of Cryptosporidium in drinking water supplies is a significant
      problem faced by the water industry. Although a variety of methods exist for the
      detection of waterborne oocysts, water utilities currently have no way of
      assessing the infectivity of detected oocysts and consequently are unable to
      accurately determine the risks posed to public health by waterborne
      Cryptosporidium. In this paper, the development of an infectivity assay for
      waterborne Cryptosporidium parvum is described. Oocysts were inoculated onto
      monolayers of Caco-2 cells and grown on microscope slides, and infections were
      detected by C. parvum specific reverse transcriptase PCR of extracted mRNA,
      targeting the heat shock protein 70 (hsp70) gene. A single infectious oocyst was
      detected by this experimental procedure. The use of concentrated samples obtained
      from 250 liters of finished water had no observable effect on the integrity of
      cell monolayers or on the infectivity of oocysts seeded into the concentrate.
      Intracellular developmental stages of the parasite were also detected by using
      fluorescently labeled antibodies. One pair of PCR primers targeting the hsp70
      gene was specific for C. parvum, while a second pair recognized all species of
      Cryptosporidium tested. The C. parvum-specific primers amplified DNA from 1 to 10
      oocysts used to seed 65 to 100 liters of concentrated environmental water samples
      and were compatible with multiplex PCR for the simultaneous detection of C.
      parvum and Giardia lambia. This paper confirms the utility of PCR for the
      detection of waterborne C. parvum and, most importantly, demonstrates the
      potential of an in vitro infectivity assay.

PMID- 9143133
TI  - Root colonization of different plants by plant-growth-promoting Rhizobium
      leguminosarum bv. trifolii R39 studied with monospecific polyclonal antisera.
AB  - Monospecific polyclonal antisera raised against Rhizobium leguminosarum bv.
      trifolii R39, a bacterium which was isolated originally from red clover nodules,
      were used to study the colonization of roots of leguminous and nonleguminous
      plants (Pisum sativum, Lupinus albus, Triticum aestivum, and Zea mays) after
      inoculation. Eight weeks after inoculation of soil-grown plants, between 0.1 and
      1% of the total bacterial population in the rhizospheres of all inoculated plants
      were identified as R. leguminosarum bv. trifolii R39. To characterize the
      associative colonization of the nonleguminous plants by R.leguminosarum bv.
      trifolii R39 in more detail, a time course study was performed with inoculated
      roots of Z. mays. R. leguminosarum bv. trifolii R39 was found almost exclusively
      in the rhizosphere soil and on the rhizoplane 4 weeks after inoculation.
      Colonization of inner root tissues was detected only occasionally at this time.
      During the process of attachment of R. leguminosarum bv. trifolii R39 to the
      rhizoplane, bacterial lipopolysaccharides were overexpressed, and this may be
      important for plant-microbe interaction. Fourteen weeks after inoculation,
      microcolonies of R. leguminosarum bv. trifolii R39 were detected in lysed cells
      of the root cortex as well as in intracellular space of central root cylinder
      cells. At the beginning of flowering (18 weeks after inoculation), the number of
      R. leguminosarum bv. trifolii R39 organisms decreased in the rhizosphere soil,
      rhizoplane, and inner root tissue.

PMID- 9143134
TI  - Resuscitation of viable but nonculturable Legionella pneumophila Philadelphia
      JR32 by Acanthamoeba castellanii.
AB  - Legionella pneumophila is an aquatic bacterium and is responsible for
      Legionnaires' disease in humans. Free-living amoebae are parasitized by
      legionellae and provide the intracellular environment required for the
      replication of this bacterium. In low-nutrient environments, however, L.
      pneumophila is able to enter a non-replicative viable but nonculturable (VBNC)
      state. In this study, L. pneumophila Philadelphia I JR 32 was suspended in
      sterilized tap water at 10(4) cells/ml. The decreasing number of bacteria was
      monitored by CFU measurements, acridine orange direct count (AODC), and
      hybridization with 16S rRNA-targeted oligonucleotide probes. After 125 days of
      incubation in water, the cells were no longer culturable on routine plating
      media; however, they were still detectable by AODC and by in situ hybridization.
      The addition of Acanthamoeba castellanii to the dormant bacteria resulted in the
      resuscitation of L. pneumophila JR 32 to a culturable state. A comparison of
      plate-grown legionellae and reactivated cells showed that the capacity for
      intracellular survival in human monocytes and intraperitoneally infected guinea
      pigs, which is considered a parameter for virulence, was not reduced in the
      reactivated cells. However, reactivation of dormant legionellae was not observed
      in the animal model.

PMID- 9143135
TI  - Molecular analysis of the Rhodococcus sp. strain H1 her gene and characterization
      of its product, a heroin esterase, expressed in Escherichia coli.
AB  - The structural gene for heroin esterase was cloned from Rhodococcus sp. strain H1
      and expressed in Escherichia coli BL21(DE3). The purified enzyme was found to be
      a tetramer with an M(r) of 137,000 and an apparent K(m) of 0.88 mM for 6
      acetylmorphine. The G-x-S-x-G motif was observed in the deduced amino acid
      sequence, suggesting that the enzyme is a serin esterase.

PMID- 9143136
TI  - Stereospecific oxidation of (R)- and (S)-1-indanol by naphthalene dioxygenase
      from Pseudomonas sp. strain NCIB 9816-4.
AB  - A recombinant Escherichia coli strain which expresses naphthalene dioxygenase
      (NDO) from Pseudomonas sp. strain NCIB 9816-4 oxidized (S)-1-indanol to trans
      (1S,3S)-indan-1,3-diol (95.5%) and (R)-3-hydroxy-1-indanone (4.5%). The same
      cells oxidized (R)-1-indanol to cis-1,3-indandiol (71%), (R)-3-hydroxy-1-indanone
      (18.2%), and cis-1,2,3-indantriol (10.8%). Purified NDO oxidized (S)-1-indenol to
      both syn- and anti-2,3-dihydroxy-1-indanol.

PMID- 9143137
TI  - Identification of Salmonella abortusovis by PCR amplification of a serovar
      specific IS200 element.
AB  - Field and collection isolates of Salmonella abortusovis carry one IS200 element
      in a distinct chromosome location. IS200 is not found in the corresponding region
      of the chromosome of other Salmonella serovars. Sequencing of the boundaries of
      the S. abortusovis-specific IS200 insertion permitted the design of primers for
      the amplification of this IS200 element by PCR. Isolates of S. abortusovis are
      identified by the amplification of a DNA fragment of about 900 bp or larger. PCR
      amplification of DNA from salmonellae other than S. abortusovis yields either a
      fragment of about 200 bp or no product. The high specificity of the assay is
      confirmed by the absence of cross-reactivity with the following templates: (i)
      sheep DNA, (ii) DNAs from abortion-causing agents other than S. abortusovis, and
      (iii) DNAs from microorganisms that do not cause abortion but are common in
      flocks.

PMID- 9143139
TI  - Molecular characterization of four members of the alpha-tubulin gene family of
      the Bermuda land crab Gecarcinus lateralis.
AB  - Four alpha-tubulin isoforms recovered from a cDNA library from regenerating limb
      buds of the Bermuda land crab Gecarcinus lateralis have been characterized. Two
      clones (alpha 1 and alpha 2) contained complete coding sequences with start and
      stop codons; the other two clones were partial, lacking 5' ends. The four
      isoforms showed high homology in their coding sequences but rather low homology
      in their non-coding regions. Identity between the nucleotide sequences of alpha 1
      and alpha 2 was 83.4%; between their predicted amino acid sequences it was 88.9%.
      The inferred number of amino acid residues for both alpha 1 and alpha 2 was 451,
      and their calculated molecular weights were 58.29 and 58.45 kDa, respectively.
      The greatest divergence in the predicted crab alpha-tubulin proteins occurred
      near the carboxy terminus, as in alpha-tubulins of other organisms. When compared
      with other species; nucleotide sequences of all four clones showed highest
      homology to alpha-tubulin genes of an insect (Drosophila melanogaster), while
      their predicted amino acid sequences were most highly homologous to an alpha
      tubulin of a mammal (Rattus norvegicus). Southern blots revealed a total of five
      to seven alpha-tubulin genes encoded in the G. lateralis genome. Northern blots
      showed single bands of approximately 2.2 kb with an alpha 1-tubulin probe and 1.9
      kb with an alpha 2-tubulin probe. mRNA levels of both tubulin isoforms appeared
      to be independently regulated at different stages of the intermolt cycle in both
      epidermis and limb buds. Western blots of 1D gels of proteins from epidermis,
      limb buds, or claw muscle showed tissue- and stage-specific changes in tubulin
      content; similar analyses on blots of 2D gels revealed differences in the number
      of alpha-tubulin isoforms that were expressed.

PMID- 9143138
TI  - Transformation of Escherichia coli with a large plasmid of Acidiphilium
      multivorum AIU 301 encoding arsenic resistance.
AB  - Acidiphilium multivorum AIU 301 isolated from acid mineral water had strong
      arsenic resistance. This bacterium harbored a number of plasmids with different
      molecular sizes. A plasmid of 56 kbp, named pKW301, was isolated from A.
      multivorum AIU 301. When pKW301 was transferred into Escherichia coli JM109 by
      electroporation, an E. coli transformant carrying pKW301 exhibited resistance to
      sodium arsenite, sodium arsenate, and mercuric (II) chloride.

PMID- 9143140
TI  - Immunolocalization of proton-ATPase in the gills of the elasmobranch, Squalus
      acanthias.
AB  - Proton-ATPase was localized to mitochondria-rich cells in the interlamellar
      region of the gills of the elasmobranch, Squalus acanthias. Localization was
      accomplished using a polyclonal antibody specific for the 70 kDa subunit of the
      (V-type) proton-ATPase as confirmed by Western blot analysis. In addition,
      significant levels of N-ethymaleimide sensitive ATPase activity (0.116 +/- 0.026
      mumol Pi.mg-1 protein.h-1) were also measured in crude gill membrane
      preparations. These data provide, for the first time, direct evidence of the
      localization of elements possibly involved in branchial acid-base (or ionic)
      regulation in elasmobranchs.

PMID- 9143141
TI  - 17 beta-estradiol effects on mast cell number and spermatogonial mitotic index in
      the testis of the frog, Rana esculenta.
AB  - Estrogen affects mast cell activity and cellular proliferation in several
      vertebrate tissues. Due to the presence of mast cells in the interstitial tissue
      of the testis and due to the annual changes of spermatogonial proliferation and
      estradiol level in the frog, Rana esculenta, we have studied the possible
      regulation of mast cell number (MCN) and primary spermatogonial mitosis exerted
      by 17 beta-estradiol (E2). MCN changed in the testis during the annual
      reproductive cycle, showing peaks in December and in May. Administration of E2
      elicited an increase of MCN both in intact and hypophysectomized frogs, and this
      effect was counteracted by tamoxifen. In vitro experiments indicated that E2
      induced an increase of both MCN and the primary spermatogonial mitotic index.
      Moreover, a significant decrease of intratesticular androgen content was measured
      in E2-treated testes. All the in vitro effects induced by E2 were counteracted by
      tamoxifen. In conclusion, our data indicate that in Rana esculenta testis E2
      increase MCN and primary spermatogonial mitotic index via intratesticular
      mechanisms. A possible involvement of the decrease of androgen levels exerted by
      E2 in the mechanism underlying the increase of MCN is also considered.

PMID- 9143142
TI  - Length of delay to birth of a second litter in dwarf hamsters (Phodopus):
      evidence for post-implantation embryonic diapause.
AB  - In Phodopus, all first litters are born after an 18 (or 19) day gestation. Birth
      of subsequent litters conceived during a postpartum estrus is routinely, but not
      always, delayed beyond 18 days. With an interval from first mating to birth of a
      second litter of as little as 36 days, Phodopus have the most compressed
      reproductive cycle of any eutherian mammal. Although pups of the Siberian hamster
      P. sungorus gain thermal independence from maternal care faster than pups of the
      Djungarian hamster P. campbelli, no species difference in the extent of delay to
      second litters was found. However, poor growth of first litter pups as a result
      of unintentional limitation of water bottle access increased delays before birth
      of a second litter in P. sungorus. Weight of pups in the first litter was a good
      predictor of the length of delay. In P. campbelli, females with large pups early
      in lactation were the only ones to deliver a second litter without delay, and
      short delays enhanced weaning weights for pups in the first litter. Patterns in
      P. sungorus were similar. The timing of the delay in second litters was
      investigated in P. campbelli. Delayed implantation during second pregnancies was
      common. Postimplantation embryonic diapause occurred in 43% of females following
      unilateral ovariohysterectomy on day 8 of a first pregnancy. As pup growth curves
      also implicated a postimplantation embryonic diapause, Phodopus may be the only
      known mammalian genus outside the order Chiroptera in which postimplantation
      diapause can occur.

PMID- 9143143
TI  - This I have learned from over 40 years of personality research.
AB  - During the over 40 years in which I have conducted personality research, I have
      had a number of insights about the research process that I thought would be worth
      sharing: an awareness of the human side of science; lessons from the person
      situation debate; lessons from comparing research on highly ego-involving natural
      events, such as sport parachuting, with laboratory analogues; the realization of
      what is wrong with the concept of the Freudian unconscious and what should be
      done to replace it and awareness of pervasive biases in the journal-reviewing
      process. Perhaps the one most general lesson I have learned is that the
      advancement of psychology as a cumulative, integrative science is hampered not so
      much by its conceptual complexity as by the difficulty of humankind to view
      itself objectively, with honesty, courage, and a willingness to surrender
      illusions.

PMID- 9143144
TI  - Vulnerability to stress: self-criticism and stress-induced changes in
      biochemistry.
AB  - It has been hypothesized that individuals who are high on the attribute of self
      criticism are particularly vulnerable to failure stress. To test this hypothesis,
      we examined the relationship between self-criticism and changes in plasma
      homovanillic acid (HVA; the metabolite of dopamine) and emotion during exposure
      to an induced-failure task. Participants consisted of 21 women. Plasma HVA and
      emotion were assessed at three time points: baseline (T1), during stress exposure
      (T2), and 40 minutes after cessation of the stressor (T3). We found that self
      criticism was significantly and positively related to changes in plasma HVA
      during stress exposure. In addition, the personality attribute was significantly
      and positively related to subjective ratings of stress and changes in scores on
      the Confusion-Bewilderment scale of the Profile of Mood States during the task.
      To our knowledge, this is the first study to report that self-criticism is
      related to stress-induced changes in biochemistry.

PMID- 9143145
TI  - Wishes, gender, personality, and well-being.
AB  - Study participants (175 men, 230 women) made three wishes and completed measures
      of the five-factor model of personality, optimism, life satisfaction, and
      depression. Common wishes were for achievement, affiliation, intimacy, and power
      as well as for happiness and money. T tests showed women were more likely to wish
      for improved appearance, happiness, and health; men were more likely to make
      power wishes and wishes for sex. Among participants who were highly involved in
      the wishing process, Extraversion was related to making more interpersonal wishes
      and wishes for positive affect. Neuroticism was related to wishes for emotional
      stability. Agreeableness and Openness to Experience related to wishes reflective
      of these traits. Conscientiousness was related to low impulsivity. Depression was
      related to making highly idiosyncratic, specific wishes, suggesting the use of
      wishful thinking as a coping mechanism. In addition, happy participants were more
      likely to rate their wishes as likely to come true. Results indicate that the
      relatively commonplace process of wishing relates to traits, gender, and well
      being.

PMID- 9143146
TI  - Personality and mate preferences: five factors in mate selection and marital
      satisfaction.
AB  - Although personality characteristics figure prominently in what people want in a
      mate, little is known about precisely which personality characteristics are most
      important, whether men and women differ in their personality preferences, whether
      individual women or men differ in what they want, and whether individuals
      actually get what they want. To explore these issues, two parallel studies were
      conducted, one using a sample of dating couples (N = 118) and one using a sample
      of married couples (N = 216). The five-factor model, operationalized in
      adjectival form, was used to assess personality characteristics via three data
      sources-self--report, partner report, and independent interviewer reports.
      Participants evaluated on a parallel 40-item instrument their preferences for the
      ideal personality characteristics of their mates. Results were consistent across
      both studies. Women expressed a greater preference than men for a wide array of
      socially desirable personality traits. Individuals differed in which
      characteristics they desired, preferring mates who were similar to themselves and
      actually obtaining mates who embodied what they desired. Finally, the personality
      characteristics of one's partner significantly predicted marital and sexual
      dissatisfaction, most notably when the partner was lower on Agreeableness,
      Emotional Stability, and Intellect-Openness than desired.

PMID- 9143147
TI  - Representations of self and other: a semantic space model.
AB  - This article describes a semantic space model of personality. According to the
      model, representations of facets of the self (e.g., actual self, ideal self) and
      of others are arrayed in a semantic space, with proximities among representations
      predicted to be associated with mood, self-evaluation, and broad personality
      dimensions. The relation of proximities among pairs of representations to
      personality and mood measures was found to be mediated by the spatial proximity
      of other representations, indicating that the representations constitute dynamic
      systems. Proximities among representations were shown to predict self-esteem and
      self-evaluative moods even after controlling for the contribution of the
      personality dimensions of Neuroticism, Extraversion, and Agreeableness.
      Generally, the semantic space model led to better predictions than did several
      related models concerning representations of self and other.

PMID- 9143148
TI  - The display of masculinity, femininity, and gender diagnosticity in self
      descriptive photo essays.
AB  - Thirty-seven college men and 57 college women assessed on Gender Diagnosticity
      (GD), Masculinity (M), and Femininity (F) created self-descriptive photo essays,
      which were then rated by six judges on 38 personality characteristics, including
      masculinity and femininity. Lay judges reliably rated men and women's masculinity
      and femininity from photo essay information. Men's GD strongly correlated with
      their judged masculinity and femininity, M with judged extraversion, and F with
      judged warmth and nurturance. However, women's GD correlated most strongly with
      their judged maladjustment and athleticism, M with dominance and extraversion,
      and F with adjustment and physical attractiveness. Naive judgments of men and
      women's masculinity-femininity were strongly linked to other judged personality
      characteristics, and physical attractiveness was correlated with judgments of
      women's but not men's masculinity and femininity. The results show that
      masculinity and femininity make sense to laypeople, are readily judged from
      multidimensional information, and that for men, GD predicts lay judgments of
      masculinity and femininity better than M and F do.

PMID- 9143149
TI  - [9th spring meeting of the Japanese Society of Allergology. Chiba, Japan. May 1
      3, 1997. Abstracts].

PMID- 9143150
TI  - [71st annual meeting of the Japanese Association for Infections Diseases.
      Sapporo, Japan. April 3-4, 1997. Abstracts].

PMID- 9143151
TI  - [The 70th general meeting of the Japanese Leprosy Association, Hirosaki, Japan.
      May 21-22, 1997. Abstracts].

PMID- 9143152
TI  - [The 101st annual meeting of the Japanese Ophthalmological Society. Kyoto, Japan,
      May 14-17, 1997. Abstracts].

PMID- 9143154
TI  - [43rd meeting of the Japanese Society of Clinical Pathology. Hamamatsu, Japan.
      November 14-16, 1997. Abstracts].

PMID- 9143155
TI  - The University Diabetes Outreach Project and the American Diabetes Association in
      collaboration with the Caribbean Food and Nutrition Institute 3rd annual
      postgraduate course and international conference. Ocho Rios, Jamaica, February 27
      March 2, 1997. Abstracts.

PMID- 9143156
TI  - Just an ACT.

PMID- 9143157
TI  - The practice of medicine is a privilege.

PMID- 9143158
TI  - Medicaid: a comparison of Oklahoma and surrounding states, 1990-1994.
AB  - Medicaid has been the "safety net" for certain low-income people. In recent
      years, many states, including Oklahoma, have determined to enroll beneficiaries
      in managed care plans in an attempt to hold down the costs. Oklahoma began
      enrolling people in 1995, and the issue will be: was the managed care approach
      successful at least in controlling costs? To prepare, expenditures for the four
      years prior to the managed care approach have been analyzed. Comparison with
      surrounding states indicates that Oklahoma was already successful with negative
      average annual growth rates for the period 1992-1994, and that Oklahoma was more
      successful than surrounding states.

PMID- 9143159
TI  - Fraud and abuse provisions in the Health Insurance Portability and Accountability
      Act: a guide to the new act for physicians.
AB  - The Health Insurance Portability and Accountability Act, many provisions of which
      became effective on January 1, 1997, will have a significant impact in the area
      of health care fraud and abuse. This article examines the fraud and abuse
      provisions of the new act from the point of view of the practicing physician. The
      greatest impact on the health care provider will come from the increased
      enforcement resources which will be available as a result of the act. The act
      also contains some particular substantive additions to health care fraud and
      abuse law which will be applicable to physicians, including provisions penalizing
      health care fraud, wrongful disclosure of individually identifiable health
      information, false certification for home care, and false statement to a health
      benefit program.

PMID- 9143160
TI  - Change offers children the best of both polio vaccines. Oklahoma State Department
      of Health and the Centers for Disease Control and Prevention.

PMID- 9143161
TI  - The State of the State's Health--a report from the Oklahoma State Board of
      Health.

PMID- 9143162
TI  - Managed care and Florida's physicians.

PMID- 9143163
TI  - "Times are changing".

PMID- 9143164
TI  - The adjuvant treatment of malignant melanoma.
AB  - Interferon alfa-2b has recently been approved by the FDA as the first effective
      adjuvant therapy for the treatment of the "high risk for recurrence" melanoma
      patient. In a landmark study (ECOG 1684), the use of high dose Interferon alfa-2b
      for one year in melanoma patients with either deep primary melanomas or resected
      nodal metastases resulted in significant increases in overall survival (p = 0.04)
      and disease-free survival (p < 0.01) compared to the control, observation arm. If
      one considers only those patients with nodal metastases (89% of the study
      population) the survival benefit associated with adjuvant Interferon alfa-2b had
      a p value of 0.008. This survival benefit is on par with the survival benefit
      experienced with the adjuvant therapy of either breast or colon cancer. Because
      of the survival benefit associated with the adjuvant therapy, one could argue
      that any melanoma patient with a significant risk of nodal metastases (tumor
      thickness greater than 1.0 mm) should have a nodal staging procedure. Lymphatic
      mapping and sentinel node biopsy techniques are the least morbid and costly
      method to obtain this information. By performing nodal staging on patients with
      melanomas greater than 1.0 mm in thickness, effective adjuvant therapy can be
      applied in a selective fashion, exposing only those patients who have the most to
      benefit to the toxicities of the therapy.

PMID- 9143165
TI  - Pathologic examination of the sentinel lymph node.
AB  - One of the most important prognostic indicators in patients with malignant
      melanoma is lymph node status. While the five-year survival of stage I and II
      patients (without clinical adenopathy) is approximately 80 percent, this drops to
      36-50 percent in patients with clinical or microscopic lymph node involvement.
      Other factors within lymph node specimens which affect disease-free and overall
      survival are the number of positive nodes (1 vs. 1-3 vs. 4 or greater) and the
      presence of extracapsular extension. Recently, the technique of sentinel
      lymphadenectomy has been developed to facilitate detection of metastatic disease
      in regional lymph nodes. Successful completion of this procedure requires a
      specialized but multidisciplinary approach, utilizing the surgeon, oncologist,
      nuclear radiologist, and pathologist. The pathologist's role is pivotal in this
      process, because identification of melanoma metastasis in the sentinel lymph
      node(s) is not only an important prognostic indicator but also dictates whether
      the patient will receive further surgery and adjuvant chemotherapy. Therefore,
      the goal of the pathologist in examining the sentinel lymph node is to maximize
      identification of nodal metastases of malignant melanoma. This is accomplished by
      following a standard protocol which fully utilizes all tissue submitted in
      concert with commonly available immunohistochemical techniques.

PMID- 9143166
TI  - The clinical relevance of sentinel lymph nodes identified with
      radiolymphoscintigraphy.
AB  - BACKGROUND: The purpose of this case report is to illustrate the utility of radio
      guided mapping of sentinel lymph nodes (SLN's) as demonstrated by the technique's
      successful identification of nodes containing metastatic disease that would have
      been left behind if only the visual-oriented vital blue dye mapping technique had
      been used. METHOD: The patient underwent preoperative lymphoscintigraphy and
      intra-operative lymphatic mapping using vital blue dye and
      radiolymphoscintigraphy using the Neoprobe (handheld gamma probe). Nodes which
      were blue and/or "hot" (i.e., radioactive counts were three times the background
      count) were considered SLN's. RESULTS: Four SLN's were harvested, all of which
      were "hot" but only one of which was both "hot" and blue. Pathology revealed that
      the two SLN's positive for metastatic disease were not blue. CONCLUSION: While
      the blue dye lymphatic mapping technique provides the surgeon with a visual road
      map in the identification of SLN's, the Neoprobe increases the success rate of
      localization when compared to vital blue dye mapping due to the reliable
      migration of radiocolloid to the SLN's in the regional basin.
      Radiolymphoscintigraphy also increases the accuracy and efficiency of the SLN
      harvest by providing a directed dissection to the level of the nodes in the
      basin. The Neoprobe increases the yield of SLN's, some of which are clinically
      relevant since they contain metastatic disease.

PMID- 9143167
TI  - Florida's undeclared epidemic: malignant melanoma.
AB  - Contrary to the trend of early diagnosis observed in other parts of the world, in
      Florida melanoma is still being discovered in the more advanced stages. This is
      characterized by thicker lesions at diagnosis, which are hallmarked by bleeding,
      itching, ulceration, and increased vertical growth. In a study of 1,626 cutaneous
      melanoma patients at the H. Lee Moffitt Cancer Center in Florida, three
      prognostic factors, tumor thickness, Clark level, and presence of ulceration in
      the primary tumor, have remained relatively constant over an eight-year period
      (1987-1994). Despite the lack of change in tumor thickness in the last four
      years, mortality rate is decreasing, possibly due to more effective treatments.
      Regardless of these apparent improvements in mortality rates, definite progress
      must be made in the early detection of malignant melanoma through the initiation
      of statewide programs of lay public and professional education. In addition, it
      is proposed that the establishment of statewide screening programs of the
      Caucasian population with skin phenotypes 1 and 2 will also facilitate the early
      diagnosis of melanoma in the future, improve the outlook for these patients, and
      begin to address a major public health problem in the state of Florida.

PMID- 9143168
TI  - Malignant melanoma: differential diagnosis of pigmented lesions.
AB  - The incidence of melanoma is rising globally despite increased awareness.
      Familiarity with the clinical signs and certain risk factors for melanoma can
      result in early recognition, and potentially influence outcome. Unfortunately,
      there are several other cutaneous tumors, both malignant and benign, that
      resemble melanoma, and may confuse and possibly delay the diagnosis. This paper
      discusses the clinical characteristics of melanoma and its most common pigmented
      simulators.

PMID- 9143169
TI  - Investment in new technology research can save future health care dollars.
AB  - OBJECTIVE: To perform a cost analysis of the emerging technology of lymphatic
      mapping for patients with malignant melanoma. DESIGN: A retrospective, computer
      aided chart and financial cost and charge review of consecutive patients with the
      diagnosis of melanoma registered at a cancer center from December, 1995 to March,
      1996. PARTICIPANTS: 73 consecutive patients with the diagnosis of Stage 1 and 2
      melanoma (cutaneous disease only) had nodal staging of their disease with either
      a sentinel node (SLN) biopsy or an elective complete node dissection (ELND). This
      was determined largely by patient choice and the protocol in operation at the
      time of the presentation of the patient to the clinic. OUTCOMES MEASURED: There
      were no deaths in the series. Patient morbidity endpoints included rates of
      infection, incidence of extremity lymphedema, development of a seroma in the
      regional nodal basin wound and wound healing. Clinical outcome was measured by
      the ability to obtain complete nodal staging information with the new lymphatic
      mapping technology, and recurrence rates in the nodal basin after a negative SLN
      biopsy. Total charges, direct costs and total costs were calculated from all
      hospital, OR, pathology and lab charges. Professional fees were included in the
      analysis. RESULTS: Group 1 patients (50) had melanomas greater than 0.76 mm in
      thickness treated with a wide local excision (WLE), lymphatic mapping and SLN
      biopsy under general anesthesia. Five patients (Group 2) had their procedure
      performed under a straight local anesthesia. Group 3 patients (18) had nodal
      staging performed with an elective node dissection. In Groups 1 and 2, if the SLN
      was positive for micrometastases, the patients were taken back to the OR for a
      complete node dissection. The total charges per patient were $13,835, $6,853 and
      $19,285, respectively. Significant dollar savings were achieved if the nodal
      staging could be accomplished with the lymphatic mapping technology (p = 0.001).
      Morbidity was significantly less in Groups 1 and 2 compared to Group 3. After a
      mean follow-up of three years, only one patient has recurred in a SLN negative
      basin. CONCLUSIONS: With 38,300 new cases of melanoma diagnosed each year in the
      United States, a projected savings of $172 million per year (general anesthesia)
      and $350 million per year (local anesthesia) could be realized if this new
      mapping technology could be incorporated into the care of the melanoma patient.
      Patient morbidity is minimized, nodal staging is complete and patients return to
      work sooner. Recently approved adjuvant therapy can be applied in a selective
      fashion, treating only those patients in which a documented benefit has been
      obtained, saving the health care system more dollars. Initial investment in
      defining the technology was minimal.

PMID- 9143170
TI  - Redefining cutaneous lymphatic flow: the necessity of preoperative
      lymphoscintigraphy in the management of malignant melanoma.
AB  - OBJECTIVE: The purpose of this study is to emphasize the instrumental role of
      preoperative lymphoscintigraphy in the surgical treatment of patients with
      malignant melanoma. SUMMARY BACKGROUND DATA: The efficacy of lymphoscintigraphy
      is reflected in its ability to reveal cutaneous lymphatic drainage to regional
      nodal basins that are at risk for melanoma metastases but not necessarily
      discernable to be at risk through standard historical anatomical guidelines or
      clinical experience. This preoperative lymphatic mapping technique has
      contributed greatly to the accuracy and efficiency of staging procedures
      including sentinel node biopsy and elective lymph node dissection. PATIENTS AND
      METHODS: After informed consent, a selected series of four patients with primary
      melanomas located in watershed areas of the body (left neck, right mid-abdomen,
      right scapula, left back) and two patients with extremity melanomas (right distal
      forearm and left ankle) underwent pre-operative lymphoscintigraphy to identify
      all basins for metastases. RESULTS: In all of the cases, lymphatic drainage
      occurred in an unusual and unexpected basin that could not have been predicted
      clinically and in three of the cases the resected basins contained positive
      sentinel nodes. If not for the preoperative lymphoscintigraphy, these nodal
      basins would not have been resected and metastatic disease would have been left
      behind. In addition, the staging of the melanoma patient would have been
      inaccurate. CONCLUSION: If the sentinel node biopsy of elective lymph node
      dissection (ELND) were based on clinical predictions only, nodes equally at risk
      for metastatic disease would not have been resected and in some cases, nodal
      basins not at risk for metastases would have been resected unnecessarily. Without
      lymphoscintigraphy, the validity and efficacy of the ELND or the sentinel node
      biopsy for nodal staging is greatly compromised. These six case studies
      illustrate the difficulty of predicating lymphatic drainage from primary sites
      located on the head and neck, truck and even the extremities and demonstrate the
      indispensability of preoperative lymphoscintigraphy in the management of
      malignant melanoma.

PMID- 9143171
TI  - Lymphatic mapping and sentinel node biopsy in patients with malignant melanoma.
AB  - Intra-operative sentinel lymph node (SLN) mapping and biopsy is a procedure that
      accurately stages the regional lymph node basin. Defined patterns of lymphatic
      drainage allow intra-operative determination of the first (sentinel) lymph node
      in the regional basin, and the absence of metastatic disease in the SLN
      accurately reflects the absence of melanoma in the remaining regional nodes. The
      use of a radiocolloid and a handheld gamma probe together with a vital blue dye
      provides optimal results, and allows for the successful identification of the
      SLN(s) in over 98 percent of the procedures. Close collaboration between
      surgeons, nuclear radiologists and pathologists is required to ensure optimal
      results. Surgical excision of the SLN allows for a more thorough and focused
      pathological examination of one or two nodes. Examination of serially sectioned
      SLNs by H&E staining, immunohistochemical staining and perhaps RT-PCR should
      reduce the number of patients with missed microscopic melanoma in the regional
      lymph nodes. Recently reported survival data from the Intergroup Melanoma Trial
      suggest that patients may benefit from identification and removal of regional
      lymph nodes that contain metastatic melanoma. Furthermore, the survival benefit
      recently reported in patients with melanoma metastatic to regional nodes
      prospectively randomized to receive high dose Interferon alfa-2b signals that the
      surgeons should aggressively examine patients for the presence of occult regional
      melanoma metastases. Intra-operative SLN mapping and SLN biopsy is a cost
      effective procedure that allows accurate identification of regional lymph nodes
      that contain metastatic melanoma.

PMID- 9143172
TI  - The new antimalarials.

PMID- 9143173
TI  - Neonatal sepsis in Karachi: factors determining outcome and mortality.
AB  - Neonatal sepsis is a major cause of morbidity and mortality among newborns in the
      developing world. In a consecutive cohort of 292 infants with culture proven
      neonatal sepsis, the mortality was 68 (22 per cent). We analysed the association
      of predisposing factors, clinical, and laboratory characteristics of the infected
      newborns with mortality by univariate methods and logistic regression analysis.
      Comparatively higher rates of mortality were seen among home-delivered newborn
      infants and those referred from other maternity facilities. The mortality was
      significantly higher among infants weighing < 1500 g and those with birth
      asphyxia (P < 0.05). The overall mortality was higher for gram negative
      infections and the highest case fatality rates were seen in infections with
      Pseudomonas species (52 per cent) and Streptococcus pneumoniae (100 per cent).
      Several clinical features suggestive of septicaemic shock and metabolic
      derangement were associated with significantly increase risk of death. Of these,
      the logistic regression model identified hypotensive shock (odds ratio 3.6) and
      acute renal failure (odds ratio 11.2) as significant factors associated with risk
      of death. Our data suggest that delayed presentation and recognition of neonatal
      sepsis is associated with rapid development of multiorgan dysfunction and
      increased risk of mortality.

PMID- 9143174
TI  - Sickle cell and G-6-PD deficiency gene in cord blood samples: experience at King
      Khalid University Hospital, Riyadh.
AB  - Cord blood samples (1039) collected at King Khalid University Hospital were
      analysed for abnormal haemoglobins using electrophoresis at alkaline and acid pH,
      for glucose-6-phosphate dehydrogenase (G-6-PD) deficiency using
      spectrophotometric method and for G-6-PD phenotypes using electrophoresis and
      specific staining. Only two samples showed the presence of Hb AS and no case of
      sickle cell anaemia was identified. The Hb S gene frequency was 0.00096. This was
      the lowest frequency identified so far in different regions of Saudi Arabia. The
      frequency of G-6-PD deficiency was calculated separately in the males and
      females, and was found to be 3.605 per cent in the males and 0.195 per cent in
      the females. Phenotyping showed the presence of G-6-PD-B+ as the normal enzyme at
      a frequency of 0.943 in both males and females and G-6-PD-A+ at a frequency of
      0.0208 in males and 0.0059 in females. The deficient variant was mainly G-6-PD
      Mediterranean which occurred at a frequency of 0.0341 and 0.0019 in males and
      females, respectively. Only one case of G-6-PD-A- was identified in the males
      giving a frequency of 0.0019. This is the first report of Hb S and G-6-PD
      deficiency genes in cord blood samples in Riyadh. Comparison of the results in
      Riyadh with values reported elsewhere showed that Riyadh had the lowest frequency
      of both Hb S and G-6-PD deficiency gene.

PMID- 9143175
TI  - The relationship between maternal-infant antibody levels and vertical
      transmission of HIV-1 infection.
AB  - This study assesses the predictive value of the ratio of HIV-1 antibodies in the
      newborn at birth to that in the mother for perinatally transmitted infection
      confirmed subsequently by age 18 months. The ratio of HIV-1 (EIA) antibody levels
      in the baby at birth to that in the seropositive mother after the first trimester
      (sequenstration index SI) was available in 114 of a perinatal cohort of 137
      infants. We related this ratio to the HIV infection status of the children by 18
      months, HIV-1 DNA PCR and HIV-specific IgA antibody detection at birth, between 3
      and 6 months, and morbidity and mortality. Thirty-five of the 137 (26 per cent)
      children were diagnosed as infected by 18 months. The mean (SD) HIV SI was 1.57
      (0.88) in 29 infected and 0.83 (0.42) in 85 uninfected infants (P < 0.0001).
      Sensitivity and specificity of a threshold SI of 1.27 (mean +/- 2 SD of
      uninfected group) for the prediction of perinatal HIV-1 infection were 41 and 98
      per cent, respectively. The reason for the higher SI in the infected babies is
      the combination of lower antibody titres in the transmitting mothers with raised
      levels in the infected babies. A similar analysis of antibody ratios showed no
      statistical differences for measles and tetanus (P > 0.1) between HIV infected
      and uninfected groups. There was a tendency to increased morbidity (Pearson's
      correlation coefficient r = 0.31) and more severe disease in those with higher
      HIV-1 SI. Three of 17 (18 per cent) peripheral blood samples from infected
      children at birth were PCR positive; all had SI's above the threshold. Overall
      sensitivity and specificity of PCR were 85 per cent each. Eleven of the 29
      infected children were HIV-1 specific IgA positive at birth; six (64 per cent) of
      these had an SI > 1.27. This simple SI of HIV-1 EIA antibodies at birth is
      comparable to elaborate techniques in its power to predict perinatally acquired
      infection. It may be a cheap, reliable and rapid screening test for vertically
      transmitted HIV-1 infection.

PMID- 9143176
TI  - HIV-1 specific immunoglobulin A antibodies as an effective marker of perinatal
      infection in developing countries.
AB  - HIV-1 specific IgA antibody testing using commercially available reagents was
      evaluated at birth to 15 months in a group of infants born to HIV-seropositive
      South African women. Following IgG depletion of serum samples, 33/35 (94 per
      cent) of the infected infants and 3/99 (3 per cent) of the uninfected infants
      showed positive IgA reactivity. Sensitivity at birth was 24 per cent and improved
      with age; 82 per cent at 3 months, 87 per cent at 6 months and 94 per cent at 12
      months. The overall positive and negative predictive values were 92 and 98 per
      cent, respectively. An evaluation of IgA and PCR in a subsample of infants
      indicated a better sensitivity of PCR within 3 months of birth, but IgA detection
      offered a higher overall sensitivity (87 v. 83 per cent) and specificity (91 v.
      85 per cent). No significant difference in IgA level was observed between
      transmitting mothers and non-transmitting mothers. A moderate correlation existed
      between IgA level in the infant and the cumulative morbidity score, however a
      stronger association was observed between high IgA levels in the infected infant
      and rapid disease progression. The viral specific IgA assay is a simple, reliable
      and cost-effective diagnostic and prognostic test for perinatal HIV infection in
      developing countries.

PMID- 9143177
TI  - A case control study of neonatal sepsis: experience from Saudi Arabia.
AB  - Sixty-one cases of neonatal septicaemia (NNS) identified by positive blood
      cultures during surveillance of infection at King Fahd Hospital of the University
      in Khobar, Saudi Arabia from September 1983-September 1988 were studied to
      evaluate the local pattern of pathogens and the risk factors for sepsis using a
      case control analysis. The incidence of NNS was 4.9 per 1000 live births (LB).
      Among inborn infants, birth weight specific sepsis rate ranged from 2 per 1000
      liveborns among infants with birth weight > or = 2500 g to 150 per 1000 liveborns
      in those weighing < or = 1500 g. Factors significantly associated with
      septicaemia were foetal distress, low Apgar score at 5 min, and requirement for
      mechanical ventilation and umbilical catheterization. Similar findings were
      obtained with infants whose mothers had pre-eclampsia. Staphylococci were the
      major Gram-positive isolate occurring in both 'early' (< or = 48 h) and 'late'
      (448 h) onset septicaemia. The study highlights the importance of knowledge of
      local epidemiology of NNS to formulate antibiotic policy. It also suggests the
      need for reporting birth weight specific rates and for a larger case control
      study of risk factors for NNS.

PMID- 9143178
TI  - Fetal growth in maternal anaemia.
AB  - The effect of maternal iron deficiency anemia on fetal growth was studied in 54
      anaemic (haemoglobin < 11.0 g/dl) mothers. Twenty-two mothers served as controls
      (haemoglobin > or = 11.0 g/dl). All the women had singleton live births at term
      gestation. The maternal iron status was assessed by serum ferritin estimation.
      The birth weight, head circumference, chest circumference, mid-arm circumference,
      and crown heel length were significantly low in infants born to women with
      moderate (haemoglobin 6.1 +/- 8.5 g/dl) and severe anaemia (haemoglobin < or =
      6.0 g/dl), in comparison to infants born to non-anaemic women. Similarly, birth
      weight, mid-arm circumference, and crown-heel length were significantly low in
      infants of women with depleted iron stores (serum ferritin < 10 micrograms/l)
      than in infants of women with serum ferritin levels of 20 micrograms/l or more.
      All indices of fetal growth showed linear relationships with maternal
      haemoglobin, as well as with serum ferritin. The growth retarding effect of
      maternal anaemia was more on fetal birth weight and mid-arm circumference than on
      other anthropometric indices of the newborn.

PMID- 9143179
TI  - Immunoglobulins and circulating immune complexes in nephrotic syndrome.
AB  - Serum immunoglobulin (IgG, IgA and IgM) levels were measured in 40 children with
      idiopathic nephrotic syndrome and 20 healthy controls. Significantly decreased
      IgG (P < 0.001), normal IgA and increased IgM (P < 0.05), averaging 92 per cent,
      99 per cent and 104 per cent of normal mean, respectively, were observed in
      active nephrotic syndrome (ANS). The mean immunoglobulin levels did not differ
      significantly among different subgroups of ANS cases. In remission, a significant
      increase in IgG (P < 0.01), a decrease in IgA (P < 0.05) and in IgM (P < 0.01)
      levels were found in comparison to their corresponding ANS values. Their
      concentrations were significantly abnormal also when compared with controls. The
      circulating immune complexes (CIC), detected by polyethylene glycol (PEG) per
      cent index, demonstrated that overall mean serum level was significantly higher
      (P < 0.01, 168 per cent of normal) in ANS patients. Among different subgroups,
      the mean level was significantly elevated (P < 0.001, 205 per cent of normal)
      only in relapsing nephrotic syndrome cases. Thus, the abnormal levels of
      immunoglobulins were found both in active as well as in remission stage of the
      disease, while elevated levels of CIC were seen only in patients with relapse.

PMID- 9143180
TI  - Rickets and protein malnutrition in northern Nigeria.
AB  - The aim of the study was to explore the relationship between protein nutritional
      status and the development of rickets in children living in northern Nigeria. The
      diagnosis of rickets in 16 children between the ages of 10 months and 7 years was
      confirmed using established, and recently developed clinical and biochemical
      parameters. Twenty-seven children devoid of skeletal stigmata were age- and sex
      matched to the rachitic patients. A battery of clinical laboratory and
      anthropometric measurements designed to assess calcium homeostasis, skeletal
      growth, the extent of bone remodeling or resorption, and protein nutritional
      status were performed on all subjects. Our central finding was that although the
      rachitic children were moderately malnourished, their protein nutritional status
      was significantly better as measured by the serum prealbumin concentration (15.4
      v. 12.5 mg/dl, P = 0.0012) when compared with the severely malnourished children
      who were devoid of any indication of rickets. This may be due, in part, to the
      fact that actively growing children are more likely to develop rickets than are
      children whose linear growth is impeded. Unexpectedly, we found that the mean
      concentrations of serum 1,25-dihydroxyvitamin D in both the rachitic and control
      group were higher than any values for the active vitamin D metabolite previously
      reported in the literature.

PMID- 9143181
TI  - Epidemiological aspects of liver abscesses in children in the Western Cape
      Province of South Africa.
AB  - A high incidence (28 per 100,000 admissions) of liver abscesses is reported in
      children from the Western Cape Province of South Africa. Of a total of 84
      childhood hepatic abscesses over a 10-year period, 51 per cent (43 patients) were
      primary pyogenic, 30 per cent (25 patients) amoebic, 2 per cent (two patients)
      Ascaris, and 17 per cent (14 patients) were culture negative. Protein calorie
      malnutrition was evident in 56 per cent of cases. Amoebic abscesses originated in
      patients from rural areas, whereas pyogenic abscesses occurred in patients from
      urban and periurban environments. Staphylococcus aureus was cultured in 85 per
      cent of pyogenic liver abscesses. Gram negative organisms were identified in four
      cases of amoebic hepatic abscess where secondary infection occurred. Co-existing
      parasites of Ascaris lumbricoides and Trichuris trichiura were identified in the
      stools of 31 per cent of patients. A low (4.8 per cent) mortality is reported for
      this series.

PMID- 9143182
TI  - Nursery outbreak of neonatal fungal arthritis treated with fluconazole.
AB  - Eight preterm infants with mean gestational age of 31.6 +/- 1.16 weeks and a mean
      birth weight of 1310 +/- 201.7 g presented at a mean postnatal age of 26 +/- 11.4
      days with knee joint swellings and pedal oedema. There was no other clinical,
      haematological or microbiological evidence of bacterial sepsis. Fungal cultures
      yielded growth of Candida spp. from blood in five, from urine in four, from
      cerebrospinal fluid in one, and from all the three babies in whom the joints were
      aspirated. Radiographic changes of metaphysitis of the involved joints were noted
      in all. All infants had received prior antibiotic therapy. No infant had received
      total parenteral nutrition or had central lines inserted. All infants were
      treated with fluconazole in doses of 7.5 mg/kg/day for 6 weeks. Six of eight were
      thriving well at 3 months of age without any evidence of residual joint disease.
      One infant succumbed to disseminated disease and one was lost to follow-up.
      Candidial arthritis is an uncommon presentation of neonatal candidiasis.
      Fluconazole therapy proved effective.

PMID- 9143183
TI  - Simplified assessment of asphyxia at birth.
AB  - A simplified clinical method of assessment of the baby soon after birth was
      evaluated and compared with the cord blood pH and 1 min Apgar score. The
      assessment recorded cry, respiration, colour, activity, reflex response, and cord
      pulsation. Sixty-two neonates born at term by normal vaginal delivery with 1 min
      Apgar score of 0-6 (n = 31) and 7-10 (n = 31) were studied. Linear correlation
      coefficient (r) and Goodman's correlation coefficient (gamma) were used for
      statistical comparison. A combination of cry, colour and activity showed the best
      correlation with cord blood pH (r = 0.3842, P < 0.01: gamma = 0.7138) and 1 min
      Apgar score (r = 0.7768, P < 0.01, gamma = 0.9393) and was as useful as the
      combination of all the six clinical parameters. Illiterate traditional birth
      attendants can be safely taught to use cry, colour, and activity for assessing
      baby's condition at birth.

PMID- 9143184
TI  - Epidemiological considerations of the age distribution of measles in India: a
      review.
AB  - This paper reviews the Indian data on age distribution of measles prior to large
      scale immunization. In metropolitan areas, the median age was about 24 months and
      virtually all the cases were recorded in children under 5, whereas median age in
      most of rural studies was < 4-< 5 years and all the persons were not affected
      until 10 years of age. The situation was in between in other areas. Since less
      than 10 per cent of the cases occurred before 9 months of age, this age is
      appropriate for routine measles immunization. The results also suggested the
      choice of age groups to be immunized during measles mass campaigns; the upper age
      may be 3 years in metropolitan city, 10 years in rural areas, and 5 years in the
      rest of the population.

PMID- 9143185
TI  - Probable transmission of acute toxoplasmosis through breast feeding.

PMID- 9143186
TI  - A prospective study of peripheral lymphadenopathy in childhood.

PMID- 9143187
TI  - The use of mid-upper-arm circumference to monitor nutritional rehabilitation
      programmes in rural Bangladesh.

PMID- 9143188
TI  - Interrater agreement in the assessment of dehydration in infants.

PMID- 9143189
TI  - Weight gain in children with asymptomatic giardiasis and iron-deficiency anaemia
      during oral iron therapy.

PMID- 9143190
TI  - Vitamin K deficiency bleeding in infancy.

PMID- 9143191
TI  - Factors related to child care increase the risk of pneumonia among children
      living in a poor community in northeast Brazil.

PMID- 9143192
TI  - Basic demographic and professional characteristics of US women physicians.
AB  - Women physicians are a rapidly growing percentage of the physician population in
      the United States; yet, their fundamental characteristics and largely unknown.
      The Women Physicians' Health Study is the first large, national study of US women
      physicians, comprising a random sample (n = 4,501 respondents) of women
      physicians aged 30 to 70. Data from the Women Physicians' Health Study showed
      that African-American and Latina or Hispanic physicians were underrepresented,
      and Asian-American and foreign-born physicians were overrepresented in proportion
      to their prevalence in the US female population. Women physicians were more
      likely to be married and less likely to have never married and less likely to
      have never married or to be divorced or widowed than other US women. Younger
      physicians were more likely to be residency trained and board-certified and to
      work more hours per week than older physicians. Younger physicians were also less
      likely to be in solo practice, government work, or inactive; they tended to be
      concentrated in group or hospital-based practices. We found that although US
      women physicians have some common characteristics that differentiate them from
      other US women, their practice and other characteristics vary substantially by
      age and specialty in ways that have not previously been reported.

PMID- 9143193
TI  - Secular trends in ischemic heart disease mortality in California versus the
      United States, 1980 to 1991.
AB  - We compare the recent trends in ischemic heart disease mortality in California
      and the United States. Because California was among the first states to have
      declines in ischemic heart disease mortality, an examination of these recent
      trends may provide important clues for upcoming national trends. Age-adjusted and
      -specific ischemic heart disease mortality rates were calculated by sex for
      persons aged 35 and older during the years 1980 to 1991. Log-linear regression
      modeling was used to estimate the average annual percentage change in mortality.
      Between 1980 and 1991, the annual age-adjusted ischemic heart disease mortality
      declined less in California than in the United States for both women (1.9% versus
      3.1%) and men (3.1% versus 3.5%). In California, it increased slightly between
      1986 and 1990 for the oldest women and men. The slower rates of decline in
      mortality of this disease in California compared with the United States and the
      rising rates among the most elderly Californians suggest that careful attention
      should be paid to these trends in death rates of and risk factors for this
      disease in California.

PMID- 9143195
TI  - Therapies for sepsis. Emerging therapies for sepsis and septic shock.

PMID- 9143194
TI  - African-American smokers and cancers of the lung and of the upper respiratory and
      digestive tracts. Is menthol part of the puzzle?
AB  - The prevalence of cigarette smoking is higher among African Americans than among
      whites. African Americans have higher rates of lung cancer than whites, although
      they smoke fewer cigarettes. To explore this black-white difference in lung
      cancer rates, I examine various aspects of tobacco use in African-American
      smokers, including the age of initiation of smoking, quantity of cigarettes
      smoked, quit rates, level of nicotine dependence, biochemical differences, and
      brand preferences, specifically menthol brand cigarettes. I also review briefly
      the sequelae of patterns of tobacco use, including rates of lung and other
      tobacco-related cancers. A preference for mentholated cigarettes by African
      Americans is well documented and is one of the most striking differences between
      African-American and white smokers. Menthol brand preference has been
      investigated in an attempt to explain the black-white differences in rates of
      cancers of the lungs and the upper respiratory and digestive tracts. Also,
      studies have evaluated smoking behavior both with and without menthol and have
      explicitly examined the question of whether menthol use helps explain the black
      white difference in lung cancer rates. The results of these studies are so far
      inconclusive with regard to the use of menthol and the risk of lung cancer
      developing. I provide practical suggestions for clinicians in counseling African
      American smokers to quit smoking and to maintain a nonsmoking status.

PMID- 9143196
TI  - Laryngeal mask airway.

PMID- 9143197
TI  - Remifentanil: an esterase-metabolized opioid.

PMID- 9143198
TI  - Advances in spinal cord stimulation.

PMID- 9143199
TI  - Use of beta-blockade to prevent death after noncardiac surgery.

PMID- 9143200
TI  - 'Practice guidelines for blood component therapy' summarized.

PMID- 9143201
TI  - Acute onset of painful ophthalmoplegia following chiropractic manipulation of the
      neck. Initial sign of intracranial aneurysm.

PMID- 9143203
TI  - Disposable needles should be the only instrument used to test sensation in
      neurologic examinations.

PMID- 9143202
TI  - Management of herpes simplex and varicella-zoster virus infections.
AB  - Herpes simplex virus and varicella-zoster virus are common infections and are
      seen frequently in clinical practice. Infection with these viruses results in
      cutaneous lesions that may be diagnosed clinically, but widely available
      laboratory testing is useful for confirmation. Asymptomatic herpes simplex virus
      shedding, or "subclinical reactivation," likely occurs in all persons infected
      with herpes simplex virus and results in the transmission of virus despite the
      absence of signs or symptoms that suggest active infection. Oral and intravenous
      acyclovir are effective in treating initial and recurrent herpes simplex and
      varicella-zoster virus infections. The daily administration of oral acyclovir as
      suppressive therapy is effective in patients with frequently recurring genital
      infection with herpes simplex virus by reducing the number of symptomatic
      recurrences and the frequency of asymptomatic virus shedding. Two new antiviral
      agents, famciclovir and valacyclovir hydrochloride, have been approved for the
      short-term treatment of recurrent genital herpes simplex virus and recurrent
      zoster in nonimmunocompromised hosts. Famciclovir and valacyclovir demonstrate
      superior pharmacokinetics compared with acyclovir and allow for less frequent
      daily dosing with higher achievable serum drug concentrations. The attenuated
      live varicella virus vaccine is now available in the United States and prevents
      primary varicella-zoster virus infection in susceptible children and adults.

PMID- 9143204
TI  - Voices of war in medical care.

PMID- 9143205
TI  - Immigrating unaccompanied minors--a neglected minority?

PMID- 9143206
TI  - Variability in systolic blood pressure--a risk factor for coronary heart disease?
AB  - Among 1,433 men of Japanese ancestry living in Hawaii with blood pressure
      measured at four different physical examinations over a 10-year period, 110
      events of definite coronary heart disease (CHD) occurred during 11.6 years of
      subsequent follow-up. Each subject's mean blood pressure, the slope of the
      regression of his blood pressure on age, and the variance of blood pressure about
      this regression line were tested for association with subsequent incident
      definite CHD. Adjusted for mean systolic blood pressure (SBP), the variance of
      SBP was significantly associated with CHD (p < 0.001); however, the slope was not
      significantly associated with CHD. Variation in body weight was an independent
      risk factor for CHD. The effect of variation in SBP was significantly higher
      among men not taking antihypertensive medication; among men taking
      antihypertension medication, the standardized relative risk was 1.00. Comparing
      men in the highest quintile of SBP variation with those in the lowest quintile,
      the relative risk of CHD was 2.0 among all subjects and 5.3 among the 1,007 men
      not taking antihypertensive medication (95% confidence interval 1.8-15.4). Some
      of the beneficial effect of taking antihypertensive medication may have been due
      to reducing the effect of SBP variance rather than simply lowering the average
      SBP.

PMID- 9143207
TI  - Families and natural history of lipids in childhood: an 18-year follow-up study.
AB  - The natural history of total cholesterol and lipoprotein cholesterol in offspring
      was studied in relation to total cholesterol levels in their parents in the
      Epidemiological Prevention Study of Zoetermeer (EPOZ). All residents of 5 or more
      years who were living in two districts in the Dutch town of Zoetermeer were
      invited to participate in a study on indicators for chronic diseases between 1975
      and 1978. In a random sample of 483 youngsters who were 5-19 years old, yearly
      measurements of cardiovascular risk factors were performed during a follow-up
      period of 18 years (average follow-up, 13.8 years). Total and subfraction
      cholesterol levels in offspring during follow-up were studied by tertiles of age
      adjusted total cholesterol in their parents. Total and low density lipoprotein
      (LDL) cholesterol levels measured from childhood into young adulthood differed
      significantly between offspring whose fathers were in the highest total
      cholesterol tertile compared with those whose fathers were in the lowest tertile,
      amounting to 0.4 mmol/liter for total cholesterol and 0.5 mmol/liter for LDL
      cholesterol. Offspring differences by maternal tertiles amounted to 0.5
      mmol/liter for total cholesterol and 0.6 mmol/liter for LDL cholesterol.
      Offspring (n = 53) with both parents in the upper cholesterol tertile had almost
      1 mmol/liter higher cholesterol levels compared with offspring (n = 51) with both
      parents in the lowest tertile, whereas offspring (n = 48) with both parents in
      the middle tertile had intermediate levels. Differences remained after adjustment
      for sex, Quetelet index, systolic and diastolic blood pressure, and use of
      alcohol, cigarettes, and oral contraceptives. Offspring group differences in
      total and LDL cholesterol were already present in childhood and persisted into
      young adulthood. There was no clear relation between offspring change in
      cholesterol levels and parental total cholesterol levels. For high density
      lipoprotein cholesterol and its subfractions, no relations with parental total
      cholesterol levels were found. Based on the evidence of a strong positive
      relation between total cholesterol levels in parents and offspring levels of
      total and LDL cholesterol measured from childhood into young adulthood, the
      authors conclude that total and LDL cholesterol levels in offspring may already
      be characterized from young age and beyond through cholesterol levels in their
      parents.

PMID- 9143208
TI  - Risk factors for hip fracture in men. Hip Fracture Study Group.
AB  - To identify risk factors for hip fracture in men, the authors conducted a case
      control study involving 20 hospitals in Philadelphia, Pennsylvania, and 14
      hospitals in Kaiser Permanente Medical Care Program of northern California. The
      356 enrolled men had been admitted with a radiologically confirmed first hip
      fracture. The 402 control men either were from the Philadelphia area or were
      members of Kaiser Permanente and were frequency matched to the cases by age and
      ZIP code or telephone exchange. Information on potential risk factors was
      obtained through personal interviews. Men in the lowest quintile of body mass had
      a greatly increased risk of hip fracture compared with men in the heaviest
      quintile (odds ratio (OR) 3.8, 95% confidence interval (CI) 2.3-6.4). Premorbid
      lower limb dysfunction was associated with increased risks for hip fracture (OR
      3.4, 95% CI 2.1-5.4). Increased risks were also observed with the use of
      cimetidine (OR 2.5, 95% CI 1.4-4.6) and psychotropic drugs (OR 2.2, 95% CI 1.4
      3.3). Smoking cigarettes or a pipe increased the risk of hip fracture, and this
      association was independent of body mass. Finally, previous physical activity was
      markedly protective. Factors thought to affect bone density as well as factors
      identified as risk factors for falls appear to be important determinants of the
      risk of hip fracture in men. Physical activity may be a particularly promising
      preventive measure for men. Additional studies of the use of cimetidine on
      osteoporosis and osteoporotic fractures are indicated.

PMID- 9143209
TI  - Gender gap in cystic fibrosis mortality.
AB  - The authors conducted the largest study to date of survival in cystic fibrosis.
      The study cohort consisted of all patients with cystic fibrosis seen at Cystic
      Fibrosis Foundation-accredited care centers in the United States between 1988 and
      1992 (n = 21,047), or approximately 85% of all US patients diagnosed with cystic
      fibrosis. Cox proportional hazards regression analysis was used to compare the
      age-specific mortality rates of males and females and to identify risk factors
      serving as potential explanatory variables for the gender-related difference in
      survival. Among the subjects 1-20 years of age, females were 60% more likely to
      die than males (relative risk = 1.6, 95% confidence interval 1.4-1.8). Outside
      this age range, male and female survival rates were not significantly different.
      The median survival for females was 25.3 years and for males was 28.4 years.
      Nutritional status, pulmonary function, and airway microbiology at a given age
      were strong predictors of mortality at subsequent ages. Nonetheless, differences
      between the genders in these parameters, as well as pancreatic insufficiency, age
      at diagnosis, mode of presentation, and race, could not account for the poorer
      survival among females. Even after adjustment for all these potential risk
      factors, females in the age range 1-20 years remained at greater risk for death
      (relative risk = 1.6, 95% confidence interval 1.2-2.1). The authors concluded
      that in 1- to 20-year-old individuals with cystic fibrosis, survival in females
      was poorer than in males. This "gender gap" was not explained by a wide variety
      of potential risk factors.

PMID- 9143210
TI  - Long-term effects of reproductive-age menstrual cycle patterns on peri- and
      postmenopausal fracture risk.
AB  - The authors examined the association between age at menarche, menstrual cycle
      characteristics between ages 28 and 32 years, and peri- and postmenopausal
      fracture risk in a cohort of 874 women who prospectively recorded menstrual cycle
      data for at least 5 years from their early 20s through their menopause. Fracture
      history was obtained with a self-administered questionnaire. The mean age of
      respondents at the time the questionnaire was completed was 73 years. Wrist
      fracture (n = 62) risk increased with increasing age at menarche (odds ratio 3.3,
      95% confidence interval 1.7-6.2) for menarche age > or = 14 years compared with
      12-13 years) and increasing mean cycle length at age 28-32 (odds ratio 2.2, 95%
      confidence interval 1.0-4.9) for > 30.5 days compared with 26.6-30.5 days).
      Similar results were seen in analyses of the combined wrist, hip, or vertebral
      fracture group (n = 92). These prospectively recorded menstrual diary data
      indicate that age at menarche and menstrual cycle patterns may have a long-term
      association with fracture risk, with effects lasting into the postmenopausal
      years.

PMID- 9143211
TI  - Comparison of two question sequences for assessing pregnancy intentions.
AB  - Unintended pregnancies can have serious health, social, and economic
      consequences. Such pregnancies may be unwanted (a baby is not wanted at any time)
      or mistimed, yet wanted (a baby is wanted eventually). Intended pregnancies are
      those conceived when desired. Reproductive health survey respondents'
      understanding of these concepts and validity of survey results may be affected by
      question order and wording. Using a randomized crossover design, National Survey
      of Family Growth (NSFG) and Demographic and Health Survey (DHS) intendedness
      questions were asked in a 1993 survey of Arizona women aged 18-44 years. Of 2,352
      ever-pregnant respondents, 25% gave discordant responses to DHS and NSFG
      questions about the most recent pregnancy. Age, marital status, household income,
      education, parity, time since pregnancy, and outcome of pregnancy were
      significantly predictive of discordant responses. DHS and NSFG questions yielded
      similar prevalence estimates of intendedness and wantedness; but young, unmarried
      respondents gave more "mistimed" responses on whichever question was asked later.
      Classifying pregnancies as intended, mistimed, or unwanted may be a problem for
      women who have not decided on lifetime reproductive preferences. Approaches to
      improving survey validity include addressing ambivalence, clarifying the
      definition of "unwanted," and, for young, unmarried women, not attempting to
      classify unintended pregnancies as mistimed or unwanted.

PMID- 9143212
TI  - Environmental factors, reproductive history, and selective fertility in farmers'
      sibships.
AB  - In a national study of births to farmers in Norway, grain farming was associated
      with short gestational age (21-24 weeks). An impact of selective fertility and
      maternal heterogeneity on the association was suspected but could not be assessed
      further in a traditional birth-based design. Thus, analyses based on the mother
      as the observational unit were performed. A total of 45,969 farmers with a first
      birth in 1967-1981 were followed for subsequent births and perinatal mortality. A
      perinatal loss increased farmers' likelihood to continue to another pregnancy,
      but this selective fertility was less dominant than in the general population due
      to a higher baseline fertility. The effect of the mother's reproductive history
      on the grain farming-midpregnancy delivery association was analyzed in 59,338
      farmers with more than one single birth in 1967-1991. A history of preterm birth
      (< 37 weeks) in previous or subsequent pregnancies both was an independent
      determinant of midpregnancy delivery and also increased the effect of grain
      exposure. Nongrain farmers with a history of only term births had 1.3
      midpregnancy deliveries per 1,000 births; grain farmers with a history of only
      term births had 1.8 cases per 1,000 (odds ratio (OR) 1.4, 95% confidence interval
      (CI) 1.0-1.9); nongrain farmers with a history of preterm birth had 6.8 cases per
      1,000 (OR 5.5, 95% CI 4.0-7.6), whereas grain farmers with a history of preterm
      birth had 13.7 cases per 1,000 (OR 11.0, 95% CI 7.7-15.9). Selective fertility
      had only a marginal impact on the association. The study demonstrates that a
      maternally based design can contribute in the assessment of joint effects of
      environmental and maternal factors.

PMID- 9143213
TI  - Measurement methods of drug consumption as a secondary judgment criterion for
      clinical trials in chronic rheumatic diseases.
AB  - Drug consumption is sometimes used as a secondary judgment criterion for clinical
      trials. Many measurement methods are available to quantify drug consumption.
      Several methods were applied in a rheumatic disease trial involving 121 patients
      with chronic low back pain who lived around Saint-Nectaire, France, and who
      participated in the trial from April to November 1993 to determine an easily used
      and practical measurement method to detect a significant drug consumption change
      over time. Analgesic and nonsteroidal antiinflammatory drugs (NSAIDs) were
      classified according to the anatomical therapeutic chemical classification.
      Consumption was quantified on a weekly basis in number of tablets (method 1),
      unit of defined daily dose (method 2), milligrams of active principle (method 3),
      and NSAID equivalence score (method 4). These methods were applied in a
      randomized clinical trial of spa therapy on sufferers of chronic low back pain.
      An analysis of variance with repeated measures showed a significant difference in
      drug consumption between treatment and control groups detected by all methods,
      except for the NSAID consumption measured with method 3. The comparison of each
      method by the relative efficiency index indicated that method 1 had a greater
      sensitivity for detecting changes of drug consumption. Tablet count appears to be
      a more sensitive and more practical method for detecting a drug consumption
      change in clinical trials.

PMID- 9143214
TI  - Reliability and validity of proxy respondent information about childhood injury:
      an assessment of a Canadian surveillance system.
AB  - The reliability and validity of proxy respondent information in the Canadian
      Hospitals Injury Reporting and Prevention Program surveillance system was
      assessed. A standardized form was used to collect data on injury date, location,
      context (activity at the time), breakdown factor (what went wrong), mechanism,
      product involvement, safety precaution use, and motor vehicle involvement. The
      test-retest method determined reliability, with the kappa coefficient quantifying
      agreement between respondent information provided in the emergency department and
      later during a telephone interview. Of 421 eligible respondents, 325 (77%)
      completed the telephone interview, with a median time to interview of 33 hours
      (range 24-70 hours). Agreement was high for all items; kappa coefficients ranged
      from 0.79 (substantial agreement) to 1.00 (perfect agreement). Reliability was
      not significantly modified by respondent view of the injury event, age of the
      child, language of the form, or level of respondent education. Validity was
      determined by measuring the agreement between respondent information and that
      provided by an independent witness. Witness information was considered to
      represent the truth. Of the 140 injury events selected, 92 (66%) had the form
      completed by both the original respondent and an independent witness. Kappa
      coefficients were greater than 0.65 for all but one item (safety precaution use),
      and the positive predictive value of respondent information for item categories
      whose prevalence was > or = 0.25 ranged from 0.82 to 0.95. The authors conclude
      that proxy respondent data on childhood injury are both reliable and valid.

PMID- 9143215
TI  - Association of Sauropus androgynus and bronchiolitis obliterans syndrome: a
      hospital-based case-control study.
AB  - In late April 1995, an outbreak of a poorly defined respiratory illness related
      to the ingestion of leaves of Sauropus androgynus was observed in southern
      Taiwan. To further evaluate the association between S. androgynus and
      bronchiolitis obliterans syndrome, a hospital-based case-control study was
      conducted with one case group and three different control groups at Veterans
      General Hospital-Kaohsiung between April and September 1995. A total of 54 cases
      (50 females, 4 males), 54 age- and sex-matched neighborhood controls, 54 matched
      routine physical check-up controls, and 54 matched self-referred patron controls
      (who had ingested S. androgynus yet without obstructive physiology) were
      interviewed for clinical symptoms, history of S. androgynus consumption, and
      potential confounding factors. All 54 cases (100%) ingested S. androgynus
      compared with only five (9%) neighborhood controls (matched odds ratio (OR)
      incalculable, p < 0.001) and two (4%) physical check-up controls (matched OR
      incalculable, p < 0.001). In the univariate analysis of 54 cases and 54 self
      referred patron controls, factors associated with an increased risk of
      bronchiolitis obliterans syndrome were methods of food preparation (uncooked
      juice vs. stir fried or boiled dishes, matched OR 10.3 (95% confidence interval
      (CI) 1.3-84.4)); preparer of the S. androgynus-containing food (vendor only vs.
      patient only or patient plus vendor, matched OR 2.8 (95% CI 1.1-7.1)); total S.
      androgynus consumption quantity (> 4,500 vs. 413-2,063 g, matched OR 10.0 (95% CI
      1.9-53.0)); duration of consumption (> 45 vs. 6-24 days, matched OR 2.1 (95% CI
      1.2-3.8)); and midterm interruption (< 2 vs. 2-5 days per week, matched OR 2.6
      (95% CI 1.1-6.1)). Additionally, multiple conditional logistic regression
      analysis of cases and self-referred patron controls revealed that a larger total
      amount of S. androgynus consumption, preparation of S. androgynus food without
      cooking, and ingesting S. androgynus food prepared by a vendor were the
      significant risk factors associated with bronchiolitis obliterans syndrome.

PMID- 9143216
TI  - Seasonality and malaria in a west African village: does high parasite density
      predict fever incidence?
AB  - In this cohort study, the authors studied the effect of blood malaria parasite
      density on fever incidence in children in an endemic area with 9 days' follow-up
      of 1- to 12-year-old children during two time periods: the end of the dry season
      (May 1993: n = 783) and the end of the rainy season (October 1993: n = 841) in
      Bougoula, West Africa (region of Sikasso, Mali). The cumulative incidence of
      fever (temperature > 38.0 degrees C) was 2.0% in the dry season and 8.2% in the
      rainy season (p < 0.0001). In the rainy season, the risk of fever was increased
      in children of ages 1-3 years (relative risk (RR) = 2.5, 95% confidence interval
      (CI) 1.6-4.1); in those with an initial parasitemia > 15,000/microliter (RR =
      2.7, 95% CI 1.4-5.4); in children with an enlarged spleen (RR = 2.0, 95% CI 1.2
      3.3); or in those with anemia (hematocrit < 30%: RR = 1.8, 95% CI 1.1-2.9). In
      the dry season, anemia was the only predictor of fever incidence. In the rainy
      season, the best predictors of fever were, in order, age (< 4 years), enlarged
      spleen, and high parasite density. Even in the higher risk groups, the cumulative
      incidence was < 20%. The authors conclude that most children with high parasite
      density do not develop fever subsequently. The association between parasite
      density and fever varies according to age and season. Since even high levels of
      parasite density do not reliably predict fever incidence, parasite density should
      be considered as just one of a group of indicators that increase the probability
      of a fever of malarial origin.

PMID- 9143217
TI  - Some questions about "Epidemiologic association between dietary calcium intake
      and blood pressure: a meta-analysis of published data".

PMID- 9143218
TI  - Noninvasive measurements of human brain temperature using volume-localized proton
      magnetic resonance spectroscopy.
AB  - Elucidation of the role of cerebral hyperthermia as a secondary factor that
      worsens outcome after brain injury, and the therapeutic application of modest
      brain hypothermia would benefit from noninvasive measurements of absolute brain
      temperature. The present study was performed to evaluate the feasibility of using
      1H magnetic resonance (MR) spectroscopy to measure absolute brain temperature in
      human subjects on a clinical imaging spectroscopy system operating at a field
      strength of 1.5 T. In vivo calibration results were obtained from swine brain
      during whole-body heating and cooling, with concurrent measurements of brain
      temperature via implanted probes. Plots of the frequency differences between the
      in vivo MR peaks of water and N-acetyl-aspartate and related compounds (NAX), or
      water and choline and other trimethylamines versus brain temperature were linear
      over the temperature range studied (28-40 degrees C). These relationships were
      used to estimate brain temperature from 1H MR spectra obtained from 10 adult
      human volunteers from 4 cm3-volumes selected from the frontal lobe and thalamus.
      Oral and forehead temperatures were monitored concurrently with MR data
      collection to verify normothermia in all the subjects studied. Temperatures
      determined using N-acetyl-aspartate or choline as the chemical shift reference
      did not differ significantly, and therefore results from these estimates were
      averaged. The brain temperature (mean +/- SD) measured from the frontal lobe
      (37.2 +/- 0.6 degrees C) and thalamus (37.7 +/- 0.6 degrees C) were significantly
      different from each other (paired t-test, p = 0.035). We conclude that 1H MR
      spectroscopy provides a viable noninvasive means of measuring regional brain
      temperatures in normal subjects and is a promising approach for measuring
      temperatures in brain-injured subjects.

PMID- 9143219
TI  - Attenuation of transient focal cerebral ischemic injury in transgenic mice
      expressing a mutant ICE inhibitory protein.
AB  - We used transgenic mice expressing a dominant negative mutation of interleukin-1
      beta converting enzyme (ICE) (C285G) in a model of transient focal ischemia in
      order to investigate the role of ICE in ischemic brain damage. Transgenic mutant
      ICE mice (n = 11) and wild-type littermates (n = 9) were subjected to 3 h of
      middle cerebral artery occlusion followed by 24 h of reperfusion. Cerebral
      infarcts and brain swelling were reduced by 44% and 46%, respectively.
      Neurological deficits were also significantly reduced. Regional CBF, blood
      pressure, core temperature, and heart rate did not differ between groups when
      measured for up to 1 h after reperfusion. Increases in immunoreactive IL-1 beta
      levels, observed in ischemic wild-type brain at 30 min after reperfusion, were
      77% lower in the mutant strain, indicating that proIL-1 beta cleavage is
      inhibited in the mutants. DNA fragmentation was reduced in the mutants 6 and 24 h
      after reperfusion. Hence, endogenous expression of an ICE inhibitor confers
      resistance to cerebral ischemia and brain swelling. Our results indicate that
      downregulation of ICE expression might provide a useful therapeutic target in
      cerebral ischemia.

PMID- 9143220
TI  - Detection of higher-order 50- and 10-kbp DNA fragments before apoptotic
      internucleosomal cleavage after transient cerebral ischemia.
AB  - DNA fragments of 50 and 10 kbp were found in ischemic brain in adult rats
      following two-vessel occlusion or in neonates following hypoxia-ischemia. These
      higher-order fragments were detected before any laddered oligonucleosomal DNA
      fragmentation characteristic of apoptosis. Both the 50- and 10-kbp fragments were
      also detected during necrosis produced by decapitation, but these led to smeared
      smaller fragments, not laddered patterns. End-group analysis showed the presence
      of both 3'-OH and 5'-OH ends in both the 50- and 10-kbp fragments but the
      predominance of 3'-OH ends in the laddered fragments. A higher proportion of 5'
      OH to 3'-OH ends was found in the 10-kbp fragment compared to the larger 50-kbp
      fragment, suggesting a selective degradation of the 50-kbp DNA fragment to the
      laddered oligonucleosomal patterns. Overall, the mode of DNA fragmentation
      appeared different from that described in classic apoptosis of thymocytes.

PMID- 9143221
TI  - Repeat positron emission tomographic studies in transient middle cerebral artery
      occlusion in cats: residual perfusion and efficacy of postischemic reperfusion.
AB  - The wider clinical acceptance of thrombolytic therapy for ischemic stroke has
      focused more attention on experimental models of reversible focal ischemia. Such
      models enable the study of the effect of ischemia of various durations and of
      reperfusion on the development of infarctions. We used high-resolution positron
      emission tomography (PET) to assess cerebral blood flow (CBF), cerebral metabolic
      rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral metabolic
      rate of glucose (CMRglc) before, during, and up to 24 h after middle cerebral
      artery occlusion (MCAO) in cats. After determination of resting values, the MCA
      was occluded by a transorbital device. The MCA was reopened after 30 min in five,
      after 60 min in 11, and after 120 min in two cats. Whereas all cats survived 30
      min MCAO, six died after 60-min and one after 120-min MCAO during 6-20 h of
      reperfusion. In those cats surviving the first day, infarct size was determined
      on serial histologic sections. The arterial occlusion immediately reduced CBF in
      the MCA territory to < 40% of control, while CMRO2 was less affected, causing an
      increase in OEF. Whereas in the cats surviving 24 h of reperfusion after 60- and
      120-min MCAO, OEF remained elevated throughout the ischemic episode, the initial
      OEF increase had already disappeared during the later period of ischemia in those
      cats that died during the reperfusion period. After 30-min MCAO, the reperfusion
      period was characterized by a transient reactive hyperemia and fast normalization
      of CBF, CMRO2, and CMRglc, and no or only small infarcts in the deep nuclei were
      found in histology. After 60- and 120-min MCAO, the extent of hyperperfusion was
      related to the severity of ischemia, decreased CMRO2 and CMRglc persisted, and
      cortical/subcortical infarcts of varying sizes developed. A clear difference was
      found in the flow/metabolic pattern between surviving and dying cats: In cats
      dying during the observation period, extended postischemic hyperperfusion
      accompanied large defects in CMRO2 and CMRglc, large infarcts developed, and
      intracranial pressure increased fatally. In those surviving the day after MCAO,
      increased OEF persisted over the ischemic episode, postischemic hyperperfusion
      was less severe and shorter, and the perfusional and metabolic defects as well as
      the final infarcts were smaller. These results stress the importance of the
      severity of ischemia for the further course after reperfusion and help to explain
      the diverging outcome after thrombolysis, where a relation between the residual
      flow and the effectiveness of reperfusion was also observed.

PMID- 9143222
TI  - Improved perfusion with rt-PA and hirulog in a rabbit model of embolic stroke.
AB  - We conducted a study using diffusion-weighted (DWI) and perfusion-weighted (PWI)
      magnetic resonance imaging (MRI) to evaluate the efficacy of thrombolysis in an
      embolic stroke model with recombinant tissue plasminogen activator (rt-PA) and
      hirulog, a novel direct-acting antithrombin. DWI can identify areas of ischemia
      minutes from stroke onset, while PWI identifies regions of impaired blood flow.
      Right internal carotid arteries of 36 rabbits were embolized using aged
      heterologous thrombi. Baseline DWI and PWI scans were obtained to confirm
      successful embolization. Four animals with no observable DWI lesion on the
      initial scan were excluded; therefore, a total of 32 animals were randomized to
      one of three treatment groups: rt-PA (n = 11), rt-PA plus hirulog (n = 11), or
      placebo (n = 10). Treatment was begun 1 h after stroke induction. Intravenous
      doses were as follows: rt-PA, 5 mg/kg over 0.5 h with 20% of the total dose given
      as a bolus; hirulog, 1 mg/kg bolus followed by 5 mg/kg over 1 h. MRI was
      performed at 2, 3, and 5 h following embolization. Six hours after embolization,
      brains were harvested, examined for hemorrhage, then prepared for histologic
      analysis. The rt-PA decreased fibrinogen levels by 73%, and hirulog prolonged the
      aPTT to four times the control value. Posttreatment areas of diffusion
      abnormality and perfusion delay were expressed as a ratio of baseline values.
      Significantly improved perfusion was seen in the rt-PA plus hirulog group
      compared with placebo (normalized ratios of the perfusion delay areas were as
      follows: placebo, 1.58, 0.47-3.59; rt-PA, 1.12, 0.04-3.95; rt-PA and hirulog,
      0.40, 0.02-1.08; p < 0.05). Comparison of diffusion abnormality ratios measured
      at 5 h showed trends favoring reduced lesion size in both groups given rt-PA
      (normalized ratios of diffusion abnormality areas were as follows: placebo, 3.69,
      0.39-15.71; rt-PA, 2.57, 0.74-5.00; rt-PA and hirulog, 1.95, 0.33-6.80; p =
      0.32). Significant cerebral hemorrhage was observed in one placebo, two rt-PA,
      and three rt-PA plus hirulog treated animals. One fatal systemic hemorrhage was
      observed in each of the rt-PA groups. We conclude that rt-PA plus hirulog
      improves cerebral perfusion but does not necessarily reduce cerebral injury. DWI
      and PWI are useful methods for monitoring thrombolysis.

PMID- 9143223
TI  - Calcineurin inhibitor, FK506, prevents reduction in the binding capacity of
      cyclic AMP-dependent protein kinase in ischemic gerbil brain.
AB  - We examined the effects of FK506, a specific inhibitor of calcineurin, on the
      binding capacity of cyclic AMP-dependent protein kinase (cAMP-DPK) in gerbils
      subjected to 2-h cerebral hemispheric ischemia. FK506 (0.1 mg/kg) was infused
      intravenously at 15 min prior to the induction of ischemia by common carotid
      artery occlusion. The binding capacity of cAMP-DPK was evaluated by
      autoradiographic analysis of the cAMP binding, and cerebral blood flow (CBF) was
      measured by the [14C] iodoantipyrine method. In the sham-operated gerbils. FK506
      significantly increased mean arterial blood pressure and tended to decrease CBF,
      suggesting that FK506 may constrict systemic blood vessels as well as cerebral
      blood vessels. On the other hand, cAMP binding was not altered by FK506 in the
      sham-operated gerbils. In the ischemia group of gerbils, FK506 prevented any
      significant reduction of cAMP binding in the hippocampus CA1 and cerebral
      cortices on the ischemic side, whereas it exerted no significant influence on the
      cAMP binding of the nonischemic side. The values of CBF were comparable between
      the vehicle-treated gerbils and FK506-treated gerbils in the ischemic regions.
      Preservation of cAMP binding indicates that intracellular signal transduction via
      cAMP-DPK can be maintained by FK506 despite ischemia, suggesting that this agent
      may be beneficial for reducing ischemic tissue damage.

PMID- 9143224
TI  - The effects of SB 206284A, a novel neuronal calcium-channel antagonist, in models
      of cerebral ischemia.
AB  - The effects of SB 206284A, 1-[7-(4-benzyloxyphenoxy)heptyl] piperidine
      hydrochloride, have been investigated in vitro on calcium and sodium currents in
      rat-cultured dorsal root ganglion (DRG) neurones and potassium-mediated calcium
      influx in rat synaptosomes. Cardiovascular hemodynamic effects in both
      anesthetized and conscious rats, and neuroprotective activity in in vivo cerebral
      ischemia models were also investigated. In the rat DRG cells, SB 206284A caused
      almost complete block of the sustained inward Ca2+ current (IC50 = 2.4 microM),
      suggesting that the compound is an effective blocker of slowly inactivating, high
      voltage calcium current. SB 206284A reduced locomotor hyperactivity in the gerbil
      bilateral carotid artery occlusion model without affecting ischemia-induced
      damage in the hippocampal CA1 region. In the rat middle cerebral artery occlusion
      model, SB 206284A reduced lesion volume in the posterior forebrain, and in the
      rat photochemical cortical lesion model, lesion volume was reduced even when
      treatment was delayed until 4 hours after occlusion. At neuroprotective doses, SB
      206284A had no cardiovascular effects. These findings show that SB 206284A is a
      novel calcium channel antagonist that shows neuroprotective properties.

PMID- 9143225
TI  - Blood glucose concentration after cardiopulmonary resuscitation influences
      functional neurological recovery in human cardiac arrest survivors.
AB  - Experimental data suggest that postischemic blood glucose concentration plays an
      important role in modulating both ischemic cerebral infarction and selective
      neuronal necrosis. This study investigated the association between functional
      neurological recovery and blood glucose concentrations in human cardiac arrest
      survivors. A group of 145 nondiabetic patients were evaluated after witnessed
      ventricular fibrillation cardiac arrest. Data regarding cardiac arrest were
      collected according to an internationally accepted protocol immediately after
      arrival. Blood glucose was measured on admission and 6, 12, and 24 h thereafter.
      To control for duration of cardiac arrest and cardiogenic shock, both known to
      influence outcome as well as blood glucose, levels, Spearman rank partial
      correlation was used. In this multivariate analysis, a high admission blood
      glucose level tended to be associated with poor neurological outcome (rs = -0.16,
      n = 142, p = 0.06). The association between high median blood glucose levels over
      24 h and poor neurological outcome was strong and statistically significant (rs =
      -0.2, n = 145, p = 0.015). High blood glucose concentrations occurring over the
      first 24 h after cardiac arrest have deleterious effects on functional
      neurological recovery. Whether cardiac arrest survivors might benefit from
      reduction of blood glucose levels needs further investigation.

PMID- 9143226
TI  - Quantification of amphetamine-induced changes in [11C]raclopride binding with
      continuous infusion.
AB  - Positron emission tomography and single-photon emission computer tomography
      receptor-binding ligands can be used to measure changes in neurotransmitter
      levels. In particular, amphetamine-induced dopamine release has been assessed
      with [11C]raclopride by paired bolus injections and with [123I]iodobenzamide by
      using a single bolus plus infusion (B/I) study. Here, we measured the change in
      [11C]raclopride-specific binding in rhesus monkeys after i.v. administration of
      0.4 mg/kg amphetamine by using both the bolus and B/I paradigms. Paired bolus
      studies (control and postamphetamine) were analyzed using compartment modeling
      and graphical analysis with a new plasma metabolite model to measure the total
      distribution volume (VT). Specific binding, calculated with three measures
      linearly proportional to the binding potential, demonstrated a 22-42% reduction
      in the postamphetamine study. VT values from B/I studies were determined by the
      tissue-to-plasma ratio at equilibrium, in addition to the bolus methods. There
      was good agreement between the control VT values between bolus and B/I studies.
      The amphetamine-induced change in specific binding in B/I studies was 19 +/- 16%,
      measured directly from tissue radioactivity levels. This study demonstrates that
      stimulus-induced changes in specific binding can be measured with a single
      [11C]raclopride study using the B/I method.

PMID- 9143227
TI  - 99mTc-HMPAO as a tracer of cerebral blood flow in newborn infants.
AB  - Studies on the kinetics of 99mTc-D,L-hexamethylpropylene amine oxime (99mTc
      HMPAO) in adults have shown that it is not an ideal tracer of CBF because it
      underestimates high-flow areas. Knowledge of the kinetics of the tracer is
      important in evaluating the studies. The kinetics of 99mTc-HMPAO in infants may
      be different from that in adults, therefore, we examined the cerebral uptake and
      retention of 99mTc-HMPAO in neonates and estimated the degree of brain-to-blood
      back diffusion by comparing corresponding 133Xe flow images and 99mTc-HMPAO
      distribution images. In addition, we measured the urinary excretion of 99mTc
      HMPAO. Regional CBF was measured using a mobile brain-dedicated, fast-rotating,
      four-head multidetector system specially designed for neonatal studies. Tracers
      were 99mTc-HMPAO (4 MBq/kg) and 133Xe (500 MBq/kg). Cerebral uptake and leak-out
      of 99mTc-HMPAO were measured by a single scintillation crystal placed over the
      frontoparietal part of the infant's head. The cerebral retention of 99mTc-HMPAO
      was analyzed in 50 infants. The mean gestational age and birth weight (95%
      confidence interval) were 34.4 weeks (32.2-35.7) and 2,326 g (1,954-2,995),
      respectively. The cerebral uptake of 99mTc-HMPAO was examined in 16 of the 50
      infants, and activity during 24 h was monitored in five. In 11 infants,
      corresponding 133Xe studies were performed. Urinary excretion was studied in 12
      infants. The maximal activity in the brain was reached 90s after i.v. injection
      and was 104% (98-111) of the stable level, which was reached approximately 3 min
      after the injection. The decay corrected leakout of the tracer during the
      following 24 h was 1.0% (0.4-1.5) per hour. The cerebral retention was calculated
      at 6.8% (6.1-7.6), highest in the group of ictal studies and lowest in premature
      infants with intracranial hemorrhage. The mean value of the fixation/clearance
      ratio alpha was estimated at 3.4 (2.8-4.4). The mean urinary excretion over 24 h
      was 19.5% (11.4-27.7) and was significantly related to renal function as
      indicated by serum urea (p = 0.02 r2 = 0.55). A four-compartment model describing
      the kinetics of 99mTc-HMPAO is shown to be valid in neonates. The cerebral
      retention of the tracer is higher in neonates because of higher extraction and
      lower initial back diffusion from brain to blood. In linearizing 99mTc-HMPAO
      distribution images, a smaller correction is necessary, and we propose a value of
      the correction factor of 3.4. In this way, 99mTc-HMPAO is a more reliable tracer
      of the distribution of CBF in neonates compared with adults. The urinary
      excretion is significantly reduced compared with adults, and the radiation dose
      to the bladder wall is reduced. The effective dose is 0.3 mSv/MBq/kg.

PMID- 9143228
TI  - Determination of the time course and extent of neurotoxicity at defined
      temperatures in cultured neurons using a modified multiwell plate fluorescence
      scanner.
AB  - The cellular and molecular mechanisms of hypoxic/ischemic neurodegeneration are
      sensitive to numerous factors that modulate the time course and degree of
      neuronal death. Among such factors is hypothermia, which can dramatically protect
      neurons from injury. To examine and control for temperature-dependent effects, we
      developed a technique that provides for a high-throughput, accurate, and
      reproducible determination of the time course and degree of neurotoxicity in
      cultured cortical neurons at precisely defined temperatures. We used a
      fluorescence multiwell plate scanner, modified by us to permit the control of
      temperature, to perform serial quantitative measurements of propidium iodide (PI)
      fluorescence in cortical neuronal cultures exposed to excitotoxic insults. In
      validating this approach, we show that these time course measurements correlate
      highly with manual counts of PI-stained cells in the same cultures (r = 0.958, p
      < 0.0001) and with lactate dehydrogenase release (r = 0.964, p < 0.0001). This
      method represents an efficient approach to mechanistic and quantitative studies
      of cell death as well as a high-throughput technique for screening new
      neuroprotective therapies in vitro.

PMID- 9143229
TI  - Endothelin-1 as a mediator of endothelial cell-pericyte interactions in bovine
      brain capillaries.
AB  - Endothelial cells and pericytes are closely associated in brain capillaries.
      Together with astrocytic foot processes, they form the blood-brain barrier.
      Capillaries were isolated from bovine brain cortex. Pure populations of
      endothelial cells and pericytes were isolated and cultured in vitro. Polarized
      monolayers of endothelial cells preferentially secreted immunoreactive endothelin
      1 (Et-1) at their abluminal (brain-facing) membrane. They did not express
      receptors for Et-1. Pericytes expressed BQ-123-sensitive ETA receptors for
      endothelins as evidenced by 125I-Et-1 binding experiments. These receptors were
      coupled to phospholipase C as demonstrated by intracellular calcium measurements
      using indo-1-loaded cells. Addition of Et-1 to pericytes induced marked changes
      in the cell morphology that were associated with a reorganization of F-actin and
      intermediate filaments. It is concluded that Et-1 is a paracrine mediator at the
      bovine blood-brain barrier and that capillary pericytes are target cells for
      endothelium-derived Et-1.

PMID- 9143230
TI  - Nitric oxide and effects of cationic polypeptides in canine cerebral arteries.
AB  - Cationic polypeptides are released by activated leukocytes and may play an
      important role in the regulation of vascular tone. Effects of cationic
      polypeptides on cerebral vascular tone have not been studied. The present
      experiments were designed to determine if synthetic cationic polypeptides, poly-L
      arginine and poly-L-lysine, affect the function of cerebral arteries. Rings of
      canine basilar arteries with and without endothelium were suspended for isometric
      force recording. Poly-L-arginine (10(-8)-10(-7) M) and poly-L-lysine (10(-8)-10(
      7).M) caused endothelium-dependent relaxations. A nitric oxide synthase
      inhibitor, NG-nitro-L-arginine methyl ester (10(-4) M), and a nitric oxide
      scavenger, oxyhemoglobin (3 x 10(-6) M), inhibited relaxations in response to
      cationic polypeptides. Negatively charged molecules, heparin (1 U/ml) and dextran
      sulfate (10 mg/ml), also inhibited relaxations to poly-L-arginine or poly-L
      lysine. Higher concentrations of poly-L-arginine (10(-6)-10(-5) M) and poly-L
      lysine (10(-6)-10(-5) M) induced endothelium-independent contractions. A protein
      kinase C inhibitor, staurosporine (10(-8) M), abolished these contractions.
      Heparin (10 U/ml) and dextran sulfate (100 mg/ml) inhibited the contractile
      effect of cationic polypeptides but did not affect contractions to phorbol 12,13
      dibutyrate. Poly-L-arginine (10(-6) M) and poly-L-lysine (10(-6) M) abolished
      endothelium-dependent relaxations in response to bradykinin (10(-10)-10(-6) M) or
      calcium ionophore A23187 (10(-9)-10(-6) M). Heparin (50 U/ml) and dextran sulfate
      (200 mg/ml) restored endothelium-dependent relaxations to bradykinin (10(-10)-10(
      6) M) in arteries exposed to poly-L-arginine (10(-6) M) or poly-L-lysine (10(-6)
      M). These studies demonstrate that in the lower concentration range (10(-8)-10(
      7) M), poly-L-arginine and poly-L-lysine induce endothelium-dependent relaxations
      by production of nitric oxide via charge-dependent activation of endothelial
      nitric oxide synthase. In the higher concentration range (10(-6)-10(-5) M),
      cationic polypeptides cause endothelium-independent contractions as well as
      impairment of endothelium-dependent relaxations in response to bradykinin and
      A23187. These contractions and inhibition of endothelium-dependent relaxations
      are also mediated by a charge-dependent mechanism and may involve activation of
      protein kinase C.

PMID- 9143231
TI  - Inhibitory effect of pregnancy on stress-induced immunosuppression through
      corticotropin releasing hormone (CRH) and dopaminergic systems.
AB  - To clarify the involvement of pregnancy in the response of the neuroendocrine
      immune system to stress, we examined splenic natural killer-cell-activity-(NKCA)
      and its relevant central and blood parameters in female virgin and pregnant rats
      (10 to 11 days gestation) exposed to forced water-immersion stress with durations
      of 90 min and 180 min. Decreases in splenic NKCA, corticotropin releasing hormone
      (CRH) in the hypothalamus, and increases in progesterone (P), beta-endorphin
      (beta EP), and dopamine (DA) metabolic ratios in the frontal cortex and nucleus
      accumbens produced by stress were recognized in the virgin rats, but not in the
      pregnant rats. Pregnancy reduced splenic NKCA in rats without stress, but
      elevated it in the rats exposed to stress with a duration of 180 min. These
      findings suggest inhibitory effects of pregnancy on stress-induced
      immunosuppression and neuroendocrine changes, thereby promoting homeostasis in
      the neuroendocrine-immune system against stress. Such enhanced homeostasis
      associated with pregnancy seemed to be mediated by the activation of placental P
      and placental or pituitary beta EP in cooperation with mesocortical and
      mesolimbic DA systems and hypothalamic CRH.

PMID- 9143232
TI  - Inhibitory effect of neuraminidase on SP-induced histamine release and TNF-alpha
      mRNA in rat mast cells: evidence of a receptor-independent mechanism.
AB  - The neuropeptide substance P (SP) is a mediator of neuro-inflammation and can
      play a role by induction of histamine release (HR) and TNF-alpha. However, its
      effect on the heterogeneous response of mast cells (MC) has not been completely
      studied. We have established that the SR can induce 25% of HR in highly purified
      rat uterine MC at diestrous but not at proestrous phases of the reproductive
      cycle and 88% of HR in peritoneal mast cells (PMC). We also found 2.2 fold
      increase in TNF-alpha mRNA at diestrous, in SP stimulated uterine MC versus
      control and 2.7 fold increase in PMC; RT and competitive PCR were used to amplify
      the TNF-alpha mRNA. We have thereafter investigated the mechanism whereby the
      binding of SP to sialic acid on the MC membrane, could trigger secretion of
      histamine and induction of TNF-alpha mRNA. The neuraminidase pretreatment (0.1
      U/ml) inhibited SP-stimulated HR from either uterine MC and PMC (98% and 50%,
      respectively) and totally inhibited SP-stimulated TNF-alpha mRNA levels. The
      neuraminidase effect was not toxic, since it was not observed in IgE mediated HR
      and TNF-alpha mRNA levels. In conclusion, the inhibitory effect of the
      neuraminidase on the SP-mediated increase of histamine and TNF-alpha mRNA,
      suggests that the SP-sialic acid interaction could have a role in the MC
      heterogeneous response.

PMID- 9143233
TI  - Innervation of the thymus in normal and bone marrow reconstituted severe combined
      immunodeficient (SCID) mice.
AB  - The innervation of the thymus was studied in SCID mice: There was a relatively
      more dense innervation pattern in SCID mice as compared to normal BALB/c mice
      (from which SCID mice are derived), including nerve fibres immunoreactive for
      protein gene product 9.5 (PGP 9.5), tyrosine hydroxylase (TH), neuropeptide
      tyrosine (NPY) and vasoactive intestinal peptide (VIP), although there was no
      reactivity to substance P (SP) or leucine enkephalin (ENK). Only a few
      acetylcholinesterase (AChE)-positive nerve fibres were observed in the SCID
      thymus. Ten weeks after the transfer of bone marrow from normal BALB/c mice into
      SCID mice no immunoreactivity to the above markers was found, nor was there any
      AChE reaction, although histologically the thymus appeared normal and dot-blot
      assays demonstrated the presence of immunoglobulin indicating a return to normal
      bone marrow function in SCID mice. Both innervation and morphology were restored
      6 months after bone marrow transfer. In conclusion, the thymus of SCID mice
      lacking thymocytes has visible neurotransmitter levels in the nerves, but after
      thymocyte repopulation by bone marrow transplantation the transmitters are
      generally not demonstrable. This indicates that the innervation may be more
      important for the establishment of the microenvironment rather than the
      maintenance of thymocyte differentiation.

PMID- 9143234
TI  - 2',3'-cyclic nucleotide 3'-phosphodiesterase: a novel candidate autoantigen in
      demyelinating diseases.
AB  - Autoaggressive T-cells specific for myelin proteins like proteolipid protein
      (PLP) and myelin basic protein (MBP) are thought to play a major role in the
      pathogenesis of demyelinating diseases of the central nervous system (CNS). 2',3'
      cyclic nucleotide 3'-phosphodiesterase (CNPase) is the third most abundant myelin
      protein in the CNS. Due to lack of supply with enough CNPase of sufficient purity
      its immunologic properties have not been studied yet. We subcloned a human CNPase
      cDNA and expressed human recombinant CNPase (rh-CNPase) in E. coli. Purification
      of the protein was achieved by Ni(2+)-chelating chromatography. Furthermore we
      describe for the first time several rh-CNPase specific T-cell lines from a
      multiple sclerosis patient and a healthy control.

PMID- 9143235
TI  - CD4 T suppressor cells mediate interferon tau protection against experimental
      allergic encephalomyelitis.
AB  - Interferon tau is a type I IFN that was originally identified as a pregnancy
      recognition hormone produced by trophoblast cells. It is as potent an antiviral
      agent as IFN alpha and IFN beta, but lacks the toxicity associated with high
      concentrations of these IFNs in tissue culture and in animal studies. We recently
      showed that IFN tau, like IFN beta, can prevent the development of experimental
      allergic encephalomyelitis (EAE). We report here that IFN tau prevents EAE in
      mice by induction of suppressor cells and suppressor factors. Suppressor cells
      can be induced by IFN tau in tissue culture, and in vivo by either
      intraperitoneal injection or by oral administration to mice. Incubation of
      suppressor cells with myelin basic protein (MBP)-sensitized T cells blocked or
      delayed the MBP-induced proliferation. Further intraperitoneal injection of
      suppressor cells into mice blocked induction of EAE by MBP. Suppressor cells
      possessed the CD4 T cell phenotype, and produced soluble suppressor factors that
      inhibited MBP activation of T cells from EAE mice. The suppressor factors were
      found to be IL-10 and TGF beta, which acted synergistically to inhibit the MBP
      activation of T cells from EAE mice. These findings are important for
      understanding the mechanism(s) by which type I IFNs protect against autoimmune
      disease.

PMID- 9143236
TI  - Oral feeding of interferon tau can prevent the acute and chronic relapsing forms
      of experimental allergic encephalomyelitis.
AB  - IFN tau is a member of the type I IFN family but unlike IFN alpha and IFN beta,
      IFN tau lacks toxicity at high concentrations. Recently, ovine IFN tau was shown
      to prevent acute induction and superantigen reactivation of experimental allergic
      encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). In this
      report, we examined the ability of IFN tau when administered by oral feeding to
      block development of EAE. Oral feeding of INF tau prevented paralysis in the
      acute form of EAE in NZW mice and chronic-relapsing EAE in SJL/J mice. In
      addition, oral feeding of IFN tau at 10(5) U/dose was as effective as
      intraperitoneal (i.p.) injection in preventing chronic-relapsing EAE, and both
      forms of IFN tau administration resulted in IL10 production. Histological
      examination revealed no inflammatory lymphocytic infiltration to the CNS in IFN
      tau treated animals as compared to controls. Prolonged treatment of IFN tau was
      shown to be necessary for chronic-relapsing EAE since removal of IFN tau
      treatment by either oral feeding or i.p. injection resulted in onset of disease.
      Lastly, sera from SJL/J mice which received prolonged IFN tau treatment by oral
      feeding exhibited little to no development of anti-IFN tau antibodies. Thus, oral
      feeding of ovine IFN tau may be a successful form of IFN tau administration for
      treatment of autoimmune diseases such as MS and may circumvent potentially
      debilitative antibody responses.

PMID- 9143237
TI  - Immune effector cell (IEC)-mediated protection from HSV-1 retinitis occurs in the
      brain.
AB  - Following uniocular anterior chamber inoculation of the KOS strain of HSV-1 into
      euthymic BALB/c mice, virus spreads from the injected eye to the brain and from
      the brain to the optic nerve and retina of the uninjected eye resulting in
      retinitis. Adoptive transfer of HSV-1-specific immune effector cells (IEC) within
      24 h of anterior chamber inoculation of virus prevents retinitis. To determine
      where protection occurs, mice were injected with HSV-1 via the anterior chamber
      route, and fluorescently-labeled HSV-1-specific-IEC or ovalbumin-specific-lymph
      node cells were adoptively transferred intravenously. The eyes and brains of
      these mice were sectioned and examined for virus-infected cells and for
      fluorescently-labeled adoptively transferred cells. None of the mice in the group
      receiving an adoptive transfer of virus-specific IEC had evidence of virus
      infection of the ipsilateral suprachiasmatic nucleus (SCN), whereas the
      ipsilateral SCN of all of the mice in the control groups were virus-positive by
      day 5 P.I. Since virus spreads from the ipsilateral SCN to the contralateral
      optic nerve and retina to cause retinitis in the uninoculated eye, the results of
      these studies suggest IEC-mediated protection from HSV-1 retinitis occurs
      proximal to the ipsilateral SCN. Furthermore, since only HSV-1-specific IEC
      conferred protection and only these cells were observed in the brain, protection
      and trafficking of cells after adoptive transfer was virus-specific.

PMID- 9143238
TI  - Increased expression of B7-1 costimulatory molecule on cerebrospinal fluid cells
      of patients with multiple sclerosis and infectious central nervous system
      disease.
AB  - The expression of the costimulatory molecule B7-1 (BB-1; CD80) and its ligand
      CD28 was investigated on peripheral blood (PB) and cerebrospinal fluid (CSF) T
      and B lymphocytes and monocytes in 11 patients with relapsing-remitting multiple
      sclerosis (MS) 21 age-matched healthy controls and 10 patients with central
      nervous system (CNS) infectious disease (CID). Three channel flow cytometry was
      used with a novel gating technique in order to unambiguously identify the low
      numbers of B lymphocytes present in normal CSF. There was a significantly higher
      fraction of B7-1+ B lymphocytes in the CSF of patients with MS (72%) and CID
      (69%) when compared with healthy individuals (53%; p < 0.0001 and p < 0.002,
      respectively). Furthermore, two patients with a clinical picture of encephalitis
      showed a profoundly increased B7-1 expression on CSF monocytes. Comparison of
      absolute numbers of B7-1+ B lymphocytes/mL CSF between MS patients and healthy
      controls revealed a highly increased frequency of these cells among MS patients
      (235 cells/mL in MS patients versus 3.9 cells/mL in controls; p < 0.0001) with no
      overlap between the groups, which was otherwise seen for all other analyzed cell
      populations. We therefore hypothesize that activated B lymphocytes expressing
      high levels of B7-1 may be of pathogenetic importance in the development and
      maintenance of the MS disease.

PMID- 9143239
TI  - Diurnal variations of interleukin-1 beta mRNA and beta-actin mRNA in rat brain.
AB  - Interleukin-1 beta (IL-1 beta) is posited to play an important physiological role
      in brain functions in addition to its better defined role in pathology. The
      experiments described herein were performed to determine if IL-1 beta mRNA and
      beta-actin display diurnal rhythms in various areas of brain. Rats were
      sacrificed at 4 h intervals across a 12:12 h light/dark cycle. Hypothalamic,
      hippocampal and cortical IL-1 beta mRNA peaked just after lights were turned on,
      declined slightly during the remaining light period and stayed low in the dark.
      There were no significant changes in IL-1 beta mRNA in brain stem or cerebellum
      samples. beta-actin mRNA levels were relatively constant across the day in the
      hypothalamus, brain stem and cerebellum. However, beta-actin mRNA levels were
      lower during the day than during the night in the hippocampus and cortex.

PMID- 9143240
TI  - Enhancement of EAE and induction of autoantibodies to T-cell epitopes in mice
      infected with a recombinant vaccinia virus encoding myelin proteolipid protein.
AB  - SJL/J mice were infected with a recombinant vaccinia virus encoding myelin
      proteolipid protein (PLP) (VVplp). Antibody responses to whole PLP and to
      encephalitogenic peptides, p139-151, p178-191 or p104-117 were measured after
      vaccination and following challenge with these three PLP peptides. Competitive
      ELISAs showed that antibodies to p139-151 and p178-191 represented the majority
      of antibodies in the anti-PLP antibody response following VVplp vaccination,
      since the antibodies to intact PLP could be inhibited 56, 35 and 1%,
      respectively, by p139-151, p178-191 and p104-117. After peptide challenge,
      epitope specific anti-peptide antibodies were enhanced. These anti-peptide
      antibodies also reacted with the intact PLP molecule. Interestingly, the mean
      titer of anti-p139-151 antibody in p139-151 challenged mice was significantly
      higher than that observed for anti-p178-191 in p178-191 and for anti-p104-117 in
      p104-117 challenged mice. Following peptide challenge, the anti-PLP IgG response
      shifted from an IgG1 to an IgG2a and 2b phenotype. In these mice, both the
      clinical disease and histological pattern of experimental allergic
      encephalomyelitis (EAE) were enhanced. The enhancement was most pronounced in the
      pathologic scores in the p139-151 challenged group followed by p104-117
      challenged mice. Thus, humoral immune responses to PLP encephalitogenic peptides
      can be generated with virus encoding a self central nervous system (CNS) protein.

PMID- 9143241
TI  - Factors controlling T-cell migration across rat cerebral endothelium in vitro.
AB  - The migration of lymphocytes through primary cultures of rat brain microvascular
      endothelial cell monolayers was examined in vitro by time-lapse videomicroscopy.
      Antigen-specific T cell line migration was dependent on the duration of culture
      (post-antigen stimulation) with exogenous interleukin-2 (IL-2). Peak migration
      (approximately 50% of T-cells during the 4 h migration assay) occurred after 4
      days of culture with IL-2 but did not coincide with maximal expression of LFA-1,
      VLA-4 or the IL-2 receptor. On unstimulated endothelia antibody blockade of LFA-1
      or ICAM-1 inhibited T-cell line migration to 8.0% and 6.8% of control values,
      respectively, whereas blocking VLA-4 and VCAM-1 had no effect. On IL-beta
      activated endothelium blocking LFA-1 and ICAM-1 was less effective (24.9% and
      27.3% of control values, respectively) and blockade of VLA-4 and VCAM-1 brought
      about a reduction to 63.0% and 68.3% of controls respectively. Inhibition of IL-2
      dependent proliferation with an IL-2 receptor blocking antibody also
      significantly inhibited T-cell migration to 22.2% of controls. Peripheral lymph
      node (PLN) lymphocytes could also be induced to migrate through untreated
      cerebral endothelial cell monolayers by cross-linking CD3 which was also time and
      IL-2-dependent with maximal migration (22.7%) occurring after three days in the
      presence of exogenous IL-2. Blocking LFA-or ICAM-1 resulted in a significant
      reduction in migration across IL-1 beta-activated endothelial cells to 17.4% and
      20.9% of control values respectively although blocking the VLA-4/VCAM-1
      interaction had no significant effect. Activation of PLN lymphocytes with
      concanavalin A for up to 5 days did not induce migration but when left in contact
      with the endothelial monolayer for 24 h migration reached 31.0%. These studies
      indicate that T-cells require a combination of signals to trigger the migratory
      phenotype which is necessary to enable them to penetrate the blood-brain barrier.

PMID- 9143242
TI  - HPRT mutant T-cell lines from multiple sclerosis patients recognize myelin
      proteolipid protein peptides.
AB  - Mutation of the hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene in a
      T-cell is believed to be an indication that the T-cell has been activated and has
      proliferated in vivo. HPRT mutant T-cell lines were generated from peripheral
      blood mononuclear cells from patients with MS and control subjects. More lines
      were isolated from the MS patients than from the control subjects. Using
      stringent criteria for recognition, none of the lines from MS-affected or control
      subjects recognized intact myelin basic protein (MBP) or myelin proteolipid
      protein (PLP) molecules. Using stringent criteria, two of the 10 MS patients
      harbored mutant lines each recognizing distinct PLP peptides (PLP peptide 40-60
      recognized by 3 lines from one patient and PLP peptide 178-191 recognized by 2
      lines from the other patient). A single line recognizing PLP peptide 89-106 was
      derived from 1 of 7 normal controls. HPRT mutant lines recognizing multiple
      epitopes of PLP which spanned much of the molecule could be isolated from MS
      patients, and to a lesser extent, normal subjects.

PMID- 9143243
TI  - Differential expression, cytokine modulation, and specific functions of type-1
      and type-2 tumor necrosis factor receptors in rat glia.
AB  - Tumor necrosis factor alpha (TNF alpha) and lymphotoxin alpha (LT alpha) induce
      pleiotropic cellular effects through low-affinity 55 kDa type-1 receptors (TNFR1,
      CD120a) and high-affinity 75 kDa type-2 receptors (TNFR2, CD120b). Both cytokines
      have potent biological effects on glial cells and are strongly implicated in the
      pathology of central nervous system (CNS) demyelinating diseases. However, to
      date, neither constitutive nor cytokine-induced TNFR expression by glial cells
      have been definitively characterized. We therefore characterized TNF receptors at
      the molecular, protein, and functional levels in rat astrocytes, microglia, and
      oligodendrocytes. Northern blotting demonstrated that all three types of glia
      constitutively transcribed a single TNFR1 mRNA. IFN gamma increased transcript
      levels in all three types of glia, but TNF alpha increased levels only in
      oligodendrocytes Microglia constitutively transcribed three distinct TNFR2 mRNAs,
      levels of which were increased by either IFN gamma or TNF alpha. In contrast,
      astrocytes and oligodendrocytes constitutively transcribed nearly undetectable
      levels of TNFR2 mRNAs, and levels were not affected by IFN gamma, TNF alpha, or
      oligodendrocyte maturation. Immunocytochemical staining of glial cells
      corroborated Northern data by demonstrating that glia express a parallel pattern
      of TNFR proteins on their cell surfaces. In co-cultures of microglia plated atop
      irradiated astrocytes, human TNF alpha (which, on mouse cells, binds TNFR1
      exclusively) induced microglial cell proliferation, whereas murine TNF alpha
      (which binds both TNFRs) did not. Collectively, the data show that microglia, a
      primary source of TNF alpha at CNS inflammatory sites, express both TNFR1 and
      TNFR2, whereas astrocytes and oligodendrocytes, whose embryological origin
      differs from that of microglia, predominantly express TNFR1. TNF alpha increases
      expression of TNFR1 by oligodendrocytes whereas it increases expression of TNFR2
      by microglia. Microglia proliferation data suggest that signals transduced
      through TNFR2 directly or indirectly inhibit signals transduced through TNFR1.
      Different patterns of TNFR expression by glia at sites of CNS inflammation may be
      critical in determining whether TNF has activational, proliferative, or cytotoxic
      effects on these cells.

PMID- 9143244
TI  - Phosphatidylserine suppresses Theiler's murine encephalomyelitis virus-induced
      demyelinating disease.
AB  - Intracerebral inoculation of susceptible strains of mice with Theiler's murine
      encephalomyelitis virus (TMEV) results in immune-mediated demyelinating disease.
      Various cytokines may play an important role in the pathogenesis of this disease.
      Tumor necrosis factor (TNF)-alpha contributes to the further development of
      perivascular cellular infiltration and demyelination in the central nervous
      system (CNS). Phosphatidylserine (PS), a major anionic phospholipid of mammalian
      cells, has been proposed to function as a regulator of immune and inflammatory
      responses, especially reducing TNF-alpha production and release in mice. We
      studied the effect of PS on TMEV-induced demyelinating disease (TMEV-IDD). We
      injected TMEV intracerebrally into susceptible SJL/J mice and induced TMEV-IDD.
      PS were injected intraperitonealy, and clinical course and various immunological
      indicators were closely studied. The results show that when PS were administered
      in the effector phase. TMEV-IDD was significantly (P < 0.01) suppressed both
      clinically and histologically. In an ELISPOT assay, the number of TNF-alpha
      producing spleen cells was low in PS treated mice compared with saline treated
      control mice. mRNA of TNF-alpha was not detected in spleen cells of mice PS
      treated in the effector phase. These data suggest that administration of PS
      suppresses TMEV-IDD by suppressing TNF-alpha production in the effector phase.

PMID- 9143245
TI  - Neuromuscular regulation of T-cell activation.
AB  - Recent investigations in our laboratory have shown that murine intestinal smooth
      muscle cells (ISMCs) can exert an immunomodulatory effect on T-cells. Therefore,
      we examined the effects of substance P, calcitonin gene-related peptide (CGRP)
      and vasoactive intestinal peptide (VIP) on the ability of ISMCs to modulate T
      cell proliferation and lymphokine generation. T-cell proliferation was observed
      when these cells were co-cultured with IFN-pretreated C57/BL6 ISMCs which
      expressed major histocompatibility complex II (MHC II), but not during T-cell co
      culture with C2D (MHC II -/-) ISMCs pretreated in the same manner. T-cell
      proliferation during co-culture with C57/BL6 ISMCs was also associated with
      significantly enhanced T-cell synthesis of IFN. When CGRP (at 10(-9) M), but not
      substance P or VIP, was added to C57/BL6 ISMCs during the IFN-pretreatment
      period. T-cell proliferation was significantly increased. However, increased T
      cell proliferation was not observed if the concentration of CGRP was increased to
      10(-6) M. At the higher concentration, addition of substance P or VIP during the
      pretreatment period significantly inhibited the subsequent T-cell proliferation.
      Pretreatment of C57/BL6 ISMCs with any of the three neuropeptides and IFN
      resulted in the diminished production of IL-4 and IFN by co-cultured T-cells. A
      similar pattern of cytokine secretion was observed during T-cell co-culture with
      IFN- and neuropeptide-pretreated C2D ISMCs except when 10(-6) M substance P was
      added; IFN secretion by co-cultured T-cells was increased 4-fold under these
      conditions. Taken together, these data show a direct modulatory role for
      neuropeptides in the interaction between ISMCs and T-cells and suggest that, in
      general, neuropeptides may dampen immune responses in the neuromuscular layers of
      the inflamed intestine.

PMID- 9143246
TI  - An antisense oligodeoxynucleotide complementary to corticotropin-releasing
      hormone mRNA inhibits rat splenocyte proliferation in vitro.
AB  - Expression of neuropeptides in immune tissues has been implicated in the
      paracrine control of immune functions. The effects of the endogenous splenic
      neuropeptide corticotropin-releasing hormone (CRH) on immune cell proliferation
      were investigated by incubating splenocytes from adult male Wistar rats in vitro
      with a specific antisense oligodeoxynucleotide probe complementary to CRH mRNA.
      Incubation of cells with 1 microgram/ml phosphodiester antisense probe for 24 h
      prior to stimulation with concanavalin A (Con A) resulted in a 30-65% decrease in
      3H-thymidine uptake compared to controls. In spleen cells incubated with a random
      base sequence (nonsense) probe the uptake of 3H-thymidine was not different to
      that in control cells. Incubation of cells with either antisense or nonsense
      phosphorothioate-protected probes resulted in variable uptake of 3H-thymidine,
      demonstrating that these probes, unlike the phosphodiester probes, have non
      specific effects on cells. Addition of synthetic CRH to the cells incubated with
      the antisense phosphodiester probe partially restored the proliferative response
      of splenocytes to Con A. Immunoreactive (ir) CRH measured by radioimmunoassay in
      splenocytes incubated with the antisense probe was significantly less than ir-CRH
      in splenocytes incubated with the nonsense probe or without probe, indicating
      that the expression of splenic CRH mRNA was specifically impaired. This
      attenuation of the cell proliferative response following reduced expression of
      splenic ir-CRH provides functional evidence for the involvement of endogenously
      synthesised immune ir-CRH in splenocyte activation.

PMID- 9143247
TI  - Detection of the soluble form of the Fas molecule in patients with multiple
      sclerosis and human T-lymphotropic virus type I-associated myelopathy.
AB  - We evaluated the presence of soluble Fas molecule (sFas) in the cerebrospinal
      fluids (CSF) and the sera of patients with multiple sclerosis (MS) or human T
      lymphotropic virus type I (HTLV-I) associated myelopathy (HAM) using an enzyme
      linked immunosorbent assay (ELISA). Patients with multiple sclerosis in the
      active phase had higher sFas serum levels than control (p < 0.005). In addition,
      significantly increased serum levels of sFas were found in patients with HAM (p <
      0.005). We found a significantly increased CSF levels of sFas in patients with
      HAM and patients with MS in the active stage (p < 0.005). These results suggest
      that serum sFas may be related to clinical activity in patients with MS and that
      Fas may play an important role in the pathogenesis of HAM.

PMID- 9143248
TI  - Macrophage infiltration at the neuromuscular junction does not contribute to AChR
      loss and age-related resistance to EAMG.
AB  - Aged rats resistant to acetylcholine receptor loss in passive transfer
      experimental autoimmune myasthenia gravis (EAMG) do not reveal infiltrating
      macrophages at the neuromuscular junction (NMJ) as observed in susceptible rats.
      It was investigated whether this age-related resistance is due to impaired
      macrophage function in these aged rats. Reconstitution of aged rats with bone
      marrow from young donors did not lead to macrophage infiltration, nor did it
      abolish resistance to EAMG. Subsequently, it was investigated whether macrophages
      are a primary cause of acetylcholine receptor (AChR) loss in EAMG or are
      attracted to the NMJ secondary to tissue damage. In lethally irradiated young
      susceptible rats infiltrating macrophages were absent from the NMJ. However,
      similar AChR losses were observed in irradiated and non-irradiated rats. These
      results suggest that macrophages do not contribute to acetylcholine receptor loss
      in the effector phase of passive transfer EAMG and that age related resistance to
      passive transfer EAMG is not primarily determined by the absence of infiltrating
      macrophages.

PMID- 9143249
TI  - Degenerate antigen recognition by CD4+ effector T cells in experimental
      autoimmune encephalomyelitis.
AB  - Peptide-specific tolerance with PLP139-151 peptide analogs was used to compare
      the fine antigen-specificity requirements at both the inductive and effector
      phases of relapsing EAE (R-EAE). A PLP139-151 analog peptide containing a single
      substitution at the primary T cell receptor (TcR) contact residue (A144) did not
      induce proliferation in PLP139-151-primed CD4+ T cells. In addition, tolerance
      induced with ECDI-treated. A144-coupled splenocytes failed to prevent the
      inductive phase of PLP139-151-induced R-EAE or to inhibit the induction of
      peptide-specific DTH indicating that naive PLP139-151-specific T cells do not
      react with the A144 peptide analog. In contrast, A144-coupled splenocytes did
      prevent the expression of the effector phase of R-EAE and inhibited the
      elicitation of peptide-specific DTH responses upon administration to mice seven
      days after immunization with PLP139-151. The results provide in vivo evidence
      that "antigen-experienced' T cells recognize a broader repertoire of antigens
      than do naive T cells and have important implications for the regulation of
      immune responses and for advancing our understanding of the pathogenesis and
      treatment of autoimmune disease.

PMID- 9143250
TI  - Inhibition of T cell superantigen responses following treatment with the kappa
      opioid agonist U50,488H.
AB  - Previous work in our laboratory has shown that cytokine production by primary
      murine macrophages, and macrophage cell lines, is inhibited following treatment
      with the kappa-opioid agonist U50,488H. Furthermore, we have found that the
      participation of both accessory cells and T cells in an antibody response is
      suppressed by this compound. We have utilized the superantigen staphylococcal
      enterotoxin B (SEB) to further examine the effects of U50,488H on accessory and T
      cell function. The results showed that the proliferative response of lymph node T
      cells to SEB presented by activated macrophages was significantly inhibited by
      the kappa-opioid agonist at concentrations as low as 100 nM. However, suppression
      of the T cell response to SEB presented by resting macrophages required 100 times
      the concentration of U50,488H. On the other hand, the production of IL-2 in
      response to lymph node T cell stimulation with SEB was not altered by the opioid
      treatment. Additional experiments utilizing the opiate antagonist naloxone and
      the kappa-selective antagonist nor-binaltorphimine (norBNI) were performed in
      order to further characterize the opioid receptor involved in the suppressive
      activity of U50,488H. Results showed that both naloxone and norBNI were able to
      block the inhibitory activity of U50,488H. Further analysis showed that the
      proliferative response of thymic T cells was more sensitive to the effects of
      U50,488H, and the response with both activated and resting macrophages was
      suppressed. In addition, the production of IL-2 by the thymic T cells was also
      inhibited by the opioid treatment. The mechanism of suppression of superantigen
      induced T cell responses is discussed.

PMID- 9143251
TI  - Induction of EAE in mice with recombinant human MOG, and treatment of EAE with a
      MOG peptide.
AB  - Myelin oligodendrocyte glycoprotein (MOG) is a transmembrane glycoprotein
      expressed on the surface of central nervous system (CNS) myelin membranes, which
      has been shown to induce experimental autoimmune encephalomyelitis (EAE) in
      rodents. Here we describe the induction of EAE in SJL and (PLJ X SJL)F1 mice with
      truncated human recombinant MOG (thr-MOG, amino acids 1-120) which has been
      expressed in insect cells in soluble form. We show that in SJL mice, immunization
      with thr-MOG produces an immune response to the 1-30 and the 81-110 regions of
      the MOG molecule. We also demonstrate effective treatment of thr-MOG-induced EAE
      in SJL mice with intravenous injections of a single peptide, MOG 91-110. These
      results support the possibility of treating MS using an antigen dependent
      approach.

PMID- 9143252
TI  - Human leukocyte antigens and cytokine expression in cerebral inflammatory
      demyelinative lesions of X-linked adrenoleukodystrophy and multiple sclerosis.
AB  - The two most common forms of X-linked adrenoleukodystrophy (X-ALD) are the
      cerebral forms (CER) with an inflammatory demyelinating reaction that resembles
      multiple sclerosis, and adrenomyeloneuropathy (AMN) which involves primarily the
      spinal cord and in which the inflammatory reaction is mild or absent. We found no
      significant association between the childhood cerebral form (CCER) or AMN and the
      human leukocyte (HLA) class I and Class II antigens including the class II DR2
      haplotypes associated with multiple sclerosis. Inflammatory cytokine (tumor
      necrosis factor-alpha, interleukin-1 beta, interleukin-4, interleukin-6 and
      interferon-gamma) gene expression was increased in multiple sclerosis brain
      lesions, as has been reported previously, but much less so in CER brain lesions.
      These findings suggest that the pathogenesis of the inflammatory response in X
      ALD differs from that in multiple sclerosis.

PMID- 9143253
TI  - Consequences of live poliovirus vaccine administration in chronic fatigue
      syndrome.
AB  - The effect of live oral polio virus vaccination on chronic fatigue syndrome (CFS)
      patients was examined in a double-blind study. CFS patients were allocated
      randomly to placebo (N = 7) or vaccine (N = 7) conditions. All controls subjects
      received the vaccine (9). Vaccine administration was not associated with clinical
      exacerbation of CFS. However, objective responses to the vaccine revealed
      differences between patients and controls: increased poliovirus isolation,
      earlier peak proliferative responses, lower T-cell subsets on certain days post
      vaccination and a trend for reduced gamma-interferon in the CFS-vaccine group.
      Polio vaccination was not found to be clinically contraindicated in CFS patients,
      however, there was evidence of altered immune reactivity and virus clearance.

PMID- 9143254
TI  - Cholinergic neuron-specific ganglioside GQ1b alpha a possible target molecule for
      serum IgM antibodies in some patients with sensory ataxia.
AB  - In neurological diseases the presence of certain anti-glycosphingolipid antibody
      species is associated with the clinical features. We recently isolated the novel
      cholinergic neuron-specific gangliosides GQ1b alpha and GT1a alpha from bovine
      brain. A monoclonal antibody specific for GQ1b alpha and GT1a alpha reacted
      strongly with the dorsal born of human spinal cord but not with human motor
      neurons. We investigated the serum antibodies to these minor gangliosides in a
      number of neurologic diseases and found that 4 patients with sensory ataxic
      neuropathy had a remarkably high IgM anti-GQ1b alpha antibody titer. GQ1b alpha
      may be a target molecule for serum IgM antibodies in some patients with sensory
      ataxic neuropathy.

PMID- 9143255
TI  - Evidence that natural autoantibodies against the nerve growth factor (NGF) may be
      potential carriers of NGF.
AB  - Nerve growth factor (NGF) was detected by enzyme-linked immunosorbent assay using
      the monoclonal anti-NGF antibody 27/21 in natural NGF autoantibodies (NGF NA)
      purified from sera of control human subjects as well as from sera of patients
      with rheumatoid arthritis, autoimmune thyroiditis and to a lesser degree in
      patients with systemic lupus erythematosus as well as in NGF NA from the synovial
      fluid of patients with spondylarthropathies. Our results suggest that NGF NA may
      be potential carriers of NGF in the circulation.

PMID- 9143256
TI  - Successful treatment of established relapsing experimental autoimmune
      encephalomyelitis in mice with a monoclonal natural autoantibody.
AB  - We postulated that humoral autoimmunity can play a beneficial role in CNS
      demyelinating diseases such as multiple sclerosis. We previously demonstrated
      that monoclonal natural autoantibody SCH94.03 suppresses CNS inflammation and
      promotes remyelination in a virus-induced model of chronic progressive multiple
      sclerosis. To further investigate the relationship between natural autoimmunity
      and CNS demyelination, we examined the effect of SCH94.03 treatment on clinical
      relapses and pathological disease in SJL/J mice with established adoptive
      transfer relapsing experimental autoimmune encephalomyelitis. Treatment with
      SCH94.03 after recovery from the initial episode of clinical disease reduced
      relapse rates by half, prolonged relapse onset by 6 days and reduced spinal cord
      demyelination and meningeal inflammation by 40%. These results are consistent
      with the hypothesized immunomodulatory function of natural autoantibodies, and
      are the first direct demonstration that natural humoral autoimmunity can be
      beneficial in an autoimmune T-cell-mediated CNS demyelinating disease.

PMID- 9143257
TI  - VII Congress of the Italian Neuroimmunology Group.

PMID- 9143258
TI  - Transforming growth factor alpha expression as a response of murine motor neurons
      to axonal injury and mutation-induced degeneration.
AB  - We previously showed that degenerating adult motor neurons of the murine mutant
      wobbler, a model of spinal muscular atrophy, express Transforming Growth Factor
      alpha (TGF alpha), a growth factor endowed with glio- and neurotrophic
      activities. Here, we evaluated whether TGF alpha expression is a general response
      of adult motor neurons to injury. Synthesis of its precursor (pro-TGF alpha) was
      investigated in another model of motoneuronal degeneration, the murine mutant
      muscle deficient, and in hypoglossal motor neurons following axonal crush and
      cut. In control conditions, motor neurons were devoid of pro-TGF alpha
      immunoreactivity. In the mutant lumbar spinal cord, pro-TGF alpha immunoreactive
      motor neurons appeared as soon as the disease developed and pro-TGF alpha
      expression persisted until the latest stages of degeneration. Motor neurons and
      astrocytes of the white matter weakly immunoreactive for the TGF alpha receptor
      were also present in both control and mutant lumbar spinal cords. Following
      hypoglossal nerve crush and cut, motoneuronal pro-TGF alpha expression was
      precocious and transient, visible at one day post-injury and lasting for only 3
      days, during which time astrocyte-like cells immunoreactive for both TGF alpha
      and its receptor appeared within the injured nucleus. Enhanced TGF alpha mRNA
      levels following nerve crush showed that activation occurred at the
      transcriptional level. These results show that upregulation of TGF alpha is an
      early and common response of adult murine motor neurons to injury, regardless of
      its experimental or genetic origin.

PMID- 9143259
TI  - Frequency of neuropathological abnormalities in very low birth weight infants.
AB  - The occurrences of histologic changes in the central nervous system of very low
      birth weight infants (500 to 1500 grams) according to gestational age and
      postnatal age are incompletely reported. In order to better understand the
      abnormalities present in this patient population, the brains of 67 very low birth
      weight infants who died after having had at least one cranial ultrasound scan
      were studied. More than half the infants were born at gestational ages of 24 to
      26 weeks, and only 28% died within 24 hours (h) of birth. The slides of the
      brains of all 67 infants were reviewed simultaneously by 3 neuropathologists who
      had to agree on the presence and/or absence of each histologic characteristic.
      Among infants who died within 24 h of birth, fully one quarter had parenchymal
      hemorrhage, 42% had petechial hemorrhages in the white matter, and more than 20%
      had hypertrophic astrocytes. These data indicate that in utero, prepartum, injury
      to the nervous system was common. Compared with infants who died before the sixth
      day, those who survived at least 6 days were twice as likely to have
      moderate/severe ventriculomegaly, rarefaction, amphophilic globules, hypertrophic
      astrocytes, macrophage foci, coagulative necrosis, and hemorrhagic necrosis than
      those who died before the 7th postnatal day. Parenchymal hemorrhage and
      moderate/severe ventriculomegaly decreased in frequency with increasing
      gestational age. On the other hand, the older the gestational age, the higher the
      likelihood of finding amphophilic globules, hypertrophic astrocytes, macrophage
      foci, and zones of coagulative necrosis upon neuropathologic examination. Our
      data indicate that several central nervous system abnormalities appear to
      increase with both older gestational age and older postnatal age for infants born
      weighing less than 1500 grams. We were unable, however, to determine the relative
      contribution of gestational age and postnatal age to the specific neuropathologic
      findings in this study.

PMID- 9143260
TI  - Transforming growth factor-beta 1 in polymyositis and dermatomyositis correlates
      with fibrosis but not with mononuclear cell infiltrate.
AB  - The idiopathic inflammatory myopathies are diseases of unknown etiology
      characterized by T cell-mediated myocytotoxicity in polymyositis and complement
      mediated angiopathy of muscle fibers in dermatomyositis. A variable degree of
      fibrosis is present in muscles in these conditions both perimysially and
      endomysially. We evaluated the expression of TGF-beta 1, a pleiotropic cytokine
      with fibrogenic and immunomodulating activity, by means of quantitative
      polymerase chain reaction and immunocytochemistry in DM and PM muscle biopsies.
      TGF-beta 1 mRNA was significantly higher in DM compared with controls, whereas in
      PM the values were not significantly different when compared with controls and
      DM. TGF-beta 1 was localized in connective tissue but did not correspond with
      mononuclear cell infiltrates. These findings suggest a correlation between TGF
      beta 1 and connective tissue proliferation in inflammatory myopathy, while its
      immunomodulatory role remains to be elucidated.

PMID- 9143261
TI  - Meningioangiomatosis is associated with neurofibromatosis 2 but not with somatic
      alterations of the NF2 gene.
AB  - Meningioangiomatosis occurs sporadically and in patients with neurofibromatosis.
      The literature, however, is unclear concerning the type of neurofibromatosis
      associated with meningioangiomatosis. Because determining which form of
      neurofibromatosis predisposes to meningioangiomatosis would clarify the genetic
      alterations of this lesion, we reviewed all reported cases of
      meningioangiomatosis associated with neurofibromatosis in light of current
      diagnostic criteria for neurofibromatosis 1 (NF1) and neurofibromatosis 2 (NF2).
      All well-documented cases of meningioangiomatosis occurred in the setting of NF2,
      implying that germline alterations of the NF2 gene predispose to
      meningioangiomatosis. To determine whether sporadic (non-NF) cases of
      meningioangiomatosis arise from somatic alterations of the same gene, we screened
      the NF2 gene for mutations in 12 sporadic cases of meningioangiomatosis and in
      constitutional DNA from 6 of these 12 patients. No mutations were found in either
      the lesional or constitutional DNA, which suggests that sporadic
      meningioangiomatosis is not a forme fruste of NF2 and that somatic alterations of
      the NF2 gene do not play a major role in sporadic meningioangiomatosis. For some
      tumor suppressor genes, germline mutations may predispose to specific tumors,
      while similar sporadic lesions only rarely suffer somatic mutations in these
      genes. The present findings suggest a similar dichotomy for the NF2 gene in
      meningioangiomatosis.

PMID- 9143262
TI  - Xenogeneic adrenal medulla graft rejection rather than survival leads to
      increased rat striatal tyrosine hydroxylase immunoreactivity.
AB  - Adrenal medulla has often been used as a donor tissue for transplantation into
      damaged central nervous system, with functional effects ranging from very good to
      nonexistent. The grafts have often been associated with morphological evidence of
      stimulated recipient dopaminergic fiber plasticity. The interpretation of these
      results has been difficult due to variable but mostly poor graft survival. The
      present study combines two experiments which evaluated the effects of
      intrastriatal xenogeneic adrenal medullary cell suspension grafts on rat
      recipients. First, bovine adrenal medulla cell suspension grafts of various
      compositions were tested for their functional and morphologic effects on
      immunosuppressed hemiparkinsonian rats. In the second experiment, graft rejection
      was allowed to occur in half of the rats in order to determine a possible
      contribution of the inflammatory/immune response to increased dopaminergic fiber
      plasticity of the recipient. At 28 days, grafts of all cell types survived well
      in immunosuppressed rats, but none of the grafted cell types was associated with
      either an amelioration of amphetamine-induced rotation or an increase in striatal
      tyrosine hydroxylase immunoreactivity around the graft site. The latter
      phenomenon was observed only in the nonimmunosuppressed rats with rejected
      grafts. Our findings strongly support the role of inflammatory/immune response to
      grafting in stimulating dopaminergic fiber plasticity and in the appearance of
      sprouting.

PMID- 9143263
TI  - Dementia with Lewy bodies versus pure Alzheimer disease: differences in
      cognition, neuropathology, cholinergic dysfunction, and synapse density.
AB  - Dementia with Lewy bodies (DLB) is the second leading cause of cognitive
      impairment among the elderly. While it is usually accompanied by the neocortical
      neuritic plaques (NP) and entorhinal neurofibrillary tangles (NFT) characteristic
      of Alzheimer disease (AD), and so can be construed as a Lewy body variant of AD
      (LBV), it also occurs in pure form as diffuse Lewy body disease (DLBD). We
      assessed cognitive status in 17 DLB patients (12 with LBV and 5 with DLBD) and
      compared the results with 12 AD subjects and 5 controls. We then sought to
      determine which neuropathologic abnormalities correlated with cognitive
      impairment. Among DLB cases, neocortical Lewy body (LB) counts, modified Braak
      stages of NFT burden in the entorhinal cortex, neocortical NP counts, and loss of
      choline acetyltransferase (ChAT) activity all correlated with dementia severity.
      Unlike AD, neocortical NFT and anti-synaptophysin reactivity were uncorrelated
      with DLB dementia. Despite comparable LB counts and ChAT losses, the DLBD were
      significantly less demented than the LBV patients. We conclude that neocortical
      LB and ChAT depletion contribute to cognitive impairment in DLB and that
      concomitant AD pathology in LBV, represented by higher Braak stages and NP,
      promotes increased dementia severity compared with that encountered in DLBD.

PMID- 9143264
TI  - Anatomic relationships of the human arcuate nucleus of the medulla: a DiI
      labeling study.
AB  - The arcuate nucleus (ARC) at the ventral surface of the human medulla has been
      historically considered a precerebellar nucleus. More recently, it has been
      implicated in central chemoreception, cardiopulmonary coupling and blood pressure
      responses. A deficiency of the ARC has been reported in a subset of putative
      human developmental disorders of ventilatory function. To investigate anatomic
      relationships of the ARC with brainstem regions involved in cardiorespiratory
      control, we applied crystals of DiI, a lipophilic dye which labels cells and cell
      processes by lateral diffusion along cell membranes, to 23 paraformaldehyde-fixed
      human fetal brainstems at 19 to 22 weeks postconceptional age. After 7 to 15.5
      months diffusion, serial frozen sections were examined by florescence microscopy.
      DiI diffusion from the ARC labeled fibers and cell bodies in the medullary raphe,
      and the external arcuate fibers. Diffusion from the medullary raphe [corrected]
      labeled the reticular formation, medullary raphe, and the ARC. Diffusion from the
      pyramid and the basis pontis (negative control) labeled the corticospinal tract,
      with no labeling of the medullary raphe or ARC. The results suggest the existence
      of cellular connections between the ARC and the caudal raphe, a region implicated
      in cardiorespiratory control.

PMID- 9143265
TI  - Aggregation of mutant Cu/Zn superoxide dismutase proteins in a culture model of
      ALS.
AB  - Mutations in the Cu/Zn-superoxide dismutase (SOD-1) gene underlie some familial
      cases of amyotrophic lateral sclerosis (FALS), a neurodegenerative disorder
      characterized by loss of cortical, brainstem, and spinal motor neurons. To
      investigate the mechanisms responsible for the toxicity of mutant enzyme, SOD-1
      cDNAs bearing mutations found in FALS patients (mSOD) were expressed in cultured
      spinal motor neurons, dorsal root ganglion (DRG) and hippocampal neurons. Many
      features of motor neuron disease seen in humans with FALS and in transgenic mouse
      models were reproduced, including preferential susceptibility of motor neurons to
      toxicity of mSOD. Abnormal cytoplasmic aggregation of mSOD protein was observed
      in mSOD-expressing motor neurons, but never in neurons expressing SODwt enzyme,
      and was followed by evidence of apoptotic cell death. Such aggregates were not
      observed in nonvulnerable neuronal populations expressing mSOD (DRG or
      hippocampal neurons). Aggregation of SOD-1 may contribute significantly to the
      death of motor neurons expressing mutations associated with FALS-1 and the
      mechanisms leading to aggregation may pertain to the specific vulnerability of
      motor neurons in this disease.

PMID- 9143266
TI  - The mean A beta load in the hippocampus correlates with duration and severity of
      dementia in subgroups of Alzheimer disease.
AB  - Using image analysis techniques to quantify the percentage area covered by the
      immunopositive marker for amyloid beta-peptide (A beta), we examined subjects
      with combinations of either early-onset or late-onset Alzheimer disease (AD) and
      either familial Alzheimer disease (FAD) or sporadic Alzheimer disease (SAD). We
      measured the mean and maximum A beta loads, in the hippocampus of each subject.
      There were no statistically significant differences in the mean A beta load
      between familial and sporadic AD subjects. Although sample sizes were too small
      for statistical testing, subjects with the epsilon 4/epsilon 4 allele of the
      apolipoprotein E (ApoE) gene had higher mean A beta loads than those with the
      epsilon 3/epsilon 3 or epsilon 3/epsilon 4 alleles. Members of the Volga German
      families (recently linked to chromosome 1) all had high mean A beta loads, and
      one of the chromosome 14-linked subjects had the highest mean A beta load while
      the other had a relatively small load, but the sample was too small for
      statistical comparisons. The duration of dementia and neuropsychological test
      scores showed a statistically significant correlation with the mean A beta load
      in the hippocampus, but not with the maximum A beta load. This difference
      indicates that the mean A beta load may be a more useful feature than the maximum
      A beta load as an objective neuropathological measure for cognitive status. This
      finding may help to improve the established methods for quantitative assessment
      of the neuropathological changes in AD.

PMID- 9143267
TI  - Soluble TNF-alpha receptors are constitutively shed and downregulate adhesion
      molecule expression in malignant gliomas.
AB  - The regulation of adhesion molecule expression in malignant gliomas by tumor
      necrosis factor-alpha (TNF) and soluble TNF receptors (TNFR) was examined in the
      malignant glioma cell line A-172 and in 2 primary glioblastoma cell cultures (LA
      492 and LA-567). A-172 cells expressed only the p55 TNF receptor transcripts and
      protein. The 2 primary cell cultures expressed both the p55 and p75 TNF
      receptors. In A-172 cells and in 1 of 2 primary glioma cell cultures, TNF
      upregulated the expression of ICAM-1 and VCAM-1, A-172 and both primary glioma
      cultures also shed their TNF receptors in the absence of activation by
      stimulating agents. Soluble p55 (sp55) receptors, but not soluble p75 (sp75)
      receptors, were found to reduce the TNF induced VCAM-1 and ICAM-1 expression in
      both the glioma cell line and the primary cell culture. Immunostaining of
      malignant glioma sections confirmed the presence of soluble TNFR and adhesion
      molecule expression in glioma cells in situ. These data suggest that soluble TNF
      receptors may play a role in the mechanism by which malignant gliomas
      downregulate the effects of infiltrating immune-competent cells.

PMID- 9143268
TI  - Atypical central neurocytoma.
AB  - The proliferative potential of central neurocytomas was determined in a biopsy
      series of 36 cases and compared with clinical outcome. The mean size of the
      growth fraction, as determined by MIB-1 labeling index (MIB-1 LI) at first
      biopsy, was 2.8 +/- 2.5 with a range of 0.1 to 8.6%. Neurocytomas with an MIB-1
      LI > 2% comprised 39% of cases and showed a close correlation with the presence
      of vascular proliferation (p = 0.0006). The Kaplan-Meier analysis showed a highly
      significant difference in disease-free survival between the 2 groups (p =
      0.0068). Over an observation time of 150 months, there was a 22% relapse among
      patients with an MIB-1 LI less than 2% and a 63% chance of relapse among those
      with an MIB-1 LI greater than 2%. We propose the term "atypical central
      neurocytoma" for the latter subset, corresponding to WHO grade II.

PMID- 9143269
TI  - Binding of malignant lymphoid cells to the white matter of the human central
      nervous system: role of different CD44 isoforms, beta 1, beta 2 and beta 7
      integrins, and L-selectin.
AB  - Spreading of reactive and malignant lymphoid cells into the brain parenchyma
      requires regulated adhesion of the lymphoid cells to the parenchymal cells and/or
      extracellular matrix of the central nervous system. A multifunctional adhesion
      molecule CD44 partially mediates binding of lymphocytes to the white matter by
      interacting with hyaluronate. To analyze which forms of CD44 and what other
      adhesion molecules mediate this binding. Namalwa cells were transfected to
      express either standard (CD44st) or variant isoforms of CD44 containing exons v6
      v10, v7-v10, and v8-v10. The binding of CD44st and CD44v6-v10 transfectants to
      human cerebellar white matter was tested and it was about 1.7- and 2-fold greater
      without and with PMA activation, respectively, compared with vector-transfected
      control cells. Hyaluronidase digestion of tissue sections decreased binding of
      CD44 expressing cells to the level of vector-transfected cells. Hermes-1, a
      monoclonal antibody recognizing the hyaluronate binding site of CD44, inhibited
      white matter adhesion of CD44v6-v10 and activated CD44st cells and binding of
      soluble hyaluronate to the CD44 transfectants. Transfectants also expressed beta
      1, beta 2 and beta 7 integrins and L-selectin, but antibodies against these
      molecules did not inhibit adhesion to the white matter. These results suggest:
      (a) Addition of exons v6-v10 to the membrane proximal region of CD44 does not
      affect lymphoid cell adhesion to the white matter. (b) The only ligand of CD44 in
      the central nervous system (CNS) white matter is hyaluronate. (c) Additional
      adhesion mechanisms other than the ones analyzed above must exist.

PMID- 9143270
TI  - Viral persistent infection affects both transcriptional and posttranscriptional
      regulation of neuron-specific molecule GAP43.
AB  - Recently, we reported that in vitro and in vivo persistent infection of neurons
      by lymphocytic choriomeningitis virus (LCMV) downregulated GAP43 expression, a
      protein involved in neuronal plasticity associated with learning and memory.
      Here, we investigated the transcriptional and posttranscriptional events
      involved. Persistent LCMV infection of PC12 cells (PC12Pi) caused reduced levels
      of GAP43 steady-state mRNA when compared to uninfected PC12 cells. In addition,
      an increase in the steady-state levels of GAP43 mRNA observed in PC12 cells in
      response to nerve growth factor (NGF) was abrogated in PC12Pi cells. Nuclear run
      on analysis revealed that the rate of GAP43 transcription was reduced threefold
      in PC12Pi cells compared to uninfected PC12 cells. Moreover, analysis of the half
      life of GAP43 mRNA indicated that NGF-mediated stabilization of GAP43 transcripts
      was significantly diminished in PC12Pi cells. Treatment of PC12Pi cells with
      basic fibroblast growth factor, dibutyryl cyclic AMP, and 12-o-tetradecanoyl
      phorbol-13-acetate, a potent activator of protein kinase C, did not increase the
      GAP43 mRNA steady-state level, suggesting that LCMV infection interferes with a
      step downstream from protein kinases A and C in the NGF signal transduction
      pathway.

PMID- 9143271
TI  - Induction of protective immunity in rodents by vaccination with a prokaryotically
      expressed recombinant fusion protein containing a respiratory syncytial virus G
      protein fragment.
AB  - A subunit approach to the development of a respiratory syncytial virus (RSV)
      vaccine was investigated. It involved the production, in Escherichia coli, of an
      RSV (Long) G protein fragment (G2Na) as a C-terminal fusion partner to an albumin
      binding region (BB) of streptococcal protein G. G2Na incorporated amino acid
      residues 130-230 and was specifically recognized by murine anti-RSV-A polyclonal
      serum. In mice, intraperitoneal immunization with BBG2Na induced high anti-RSV-A
      serum ELISA titers and low to moderate neutralization activity. The immune
      response induced by BBG2Na demonstrated a potent protective efficacy against
      upper and lower respiratory tract RSV-A infection. The immunogenicity and
      protective efficacy of BBG2Na was maintained for at least 47 and 48 weeks,
      respectively, and was as potent and durable as live RSV-A administered in a
      similar fashion. Intramuscular immunization of cotton rats with BBG2Na protected
      lungs from both homologous and heterologous virus challenge. In contrast to mice,
      however, cotton rat nasal tracts were not protected after BBG2Na immunization.
      Consistent with antibody-mediated protection, virus was cleared within 24 hr from
      the lungs of BBG2Na-immunized mice. The anti-RSV-A antibodies induced in mice
      were exclusively of the IgG1 isotype and were detected in the serum, lungs, and
      nasal tracts. Passive transfer of these antibodies prevented acute, and
      eliminated chronic, RSV-A lung infection in normal and immunodeficient mice,
      respectively, confirming that such antibodies are important and sufficient for
      BBG2Na-induced pulmonary protection. Our results clearly demonstrate that BBG2Na
      contains an important immunogenic domain of the RSV G protein. The prokaryotic
      origin of this protein indicates that glycosylation of the RSV G protein is not
      necessary for protective efficacy. Thus, BBG2Na has potential as an RSV subunit
      vaccine.

PMID- 9143272
TI  - Long terminal repeat U3 length polymorphism of human foamy virus.
AB  - Size determination of the long terminal repeat (LTR) of an early (1985) and a
      more recent (1993) passage of wild-type human foamy virus (HFV) revealed that the
      virus has undergone substantial deletions in the U3 region upon replication in
      tissue culture. Two LTR deletion variants (HSRV1 and 2) have been characterized
      in the past and used to construct molecular clones which are replication
      competent in cell culture. We now report the molecular cloning, sequencing, and
      biological characterization of an HFV genome with full-length LTR (pHFV2).
      Sequence analysis revealed that the deletions in HSRV1 and 2 are nonrandom and
      probably occurred by misalignment during reverse transcription. The comparative
      analysis of HFV2 and the variant with the largest U3 deletion, HSRV2, revealed a
      differential ability to replicate in human cell cultures. While HSRV2 replicated
      faster in diploid human fibroblasts, cells which have been used extensively for
      amplification of HFV in the past, replication of HFV2 was faster in a
      lymphoblastoid cell line. Reporter gene assays indicated that the cell-type
      specific ability of the LTRs to respond to the viral transcriptional
      transactivator may be a likely, reason for the different growth properties of
      both viruses and for the occurrence of the HFV U3 deletions. In foamy virus
      infected chimpanzees only the full-length type of LTR was observed; however, the
      HSRV1 deletion variant was detected as the dominating virus in an accidentally
      HFV-infected human.

PMID- 9143273
TI  - Analyses of disulfides present in the rubella virus E1 glycoprotein.
AB  - The surface of Rubella virus contains the glycoproteins E1 and E2. The E1 protein
      induces neutralizing antibodies and has been implicated in the process of
      recognition of cellular receptors. To gain information on the structural
      organization of the E1 protein we have analyzed the disulfide bonds present
      within this molecule. The reactivity of the protein with radioactively labeled
      iodoacetic acid indicates that all 20 cysteine residues present in the ectodomain
      of the E1 protein are involved in disulfide formation. E1 protein was purified by
      preparative SDS-PAGE under nonreducing conditions from virus particles grown in
      tissue culture in the presence of [35S]cysteine. The purified protein was
      digested with a number of proteases followed by reversed phase high-performance
      liquid chromatography (HPLC). [35S]cysteine-containing peptides were identified
      and characterized by N-terminal amino acid sequence determination. These analyses
      identified the following eight disulfide bridges: C(1)-C(2); C(3)-C(15); C(6)
      C(7); C(9)-C(10); C(11)-C(12); C(13)-C(14); C(17)-C(18); and C(19)-C(20). The two
      disulfide bridges formed by the residues C(4), C(5), C(8), and C(16) have not
      been identified with certainty, but a likely organization can be derived. The
      data obtained are discussed in the context of a possible structural and
      functional organization of the E1 protein.

PMID- 9143274
TI  - Alphavirus budding is dependent on the interaction between the nucleocapsid and
      hydrophobic amino acids on the cytoplasmic domain of the E2 envelope
      glycoprotein.
AB  - The interaction between the nucleocapsid core and the glycoprotein spikes is a
      critical component in the budding process of alphaviruses. A molecular model was
      previously proposed which suggested that this interaction was mediated by the
      binding of the cytoplasmic domain of glycoprotein E2 into a hydrophobic pocket
      found on the surface of the nucleocapsid protein [S. Lee, K. E. Owen, H.-K. Choi,
      H. Lee, G. Lu, G. Wengler, D. T. Brown, M. G. Rossmann, and R. J. Kuhn (1996)
      Structure 4, 531-541; U. Skoging, M. Vihinen, L. Nilsson, and P. Liljestrom
      (1996) Structure 4, 519-529]. Two hydrophobic amino acids in the cytoplasmic
      domain of E2 were predicted to be important in the contact between the proteins.
      One of the residues, Y400 (Sindbis virus numbering), had previously been shown by
      mutational studies to be important in the budding of Semliki Forest virus [H.
      Zhao, B. Lindqvist, H. Garoff, C. H. von Bonsdorf, and P. Liljestrom (1994) EMBO
      J. 13, 4204-4211]. The role of the second residue, L402, had not been examined.
      By creating a panel of amino acid substitutions at this residue, followed by
      phenotypic analysis of rescued mutant viruses, we now show that L402 is critical
      for the production of Sindbis virus. Substitutions at this amino acid inhibit
      budding, and the data suggest the L402 plays an important role in the
      interaction, between the glycoprotein and the nucleocapsid core. These data
      support the model and suggest that the proposed molecular interactions are
      important for the budding of alphaviruses from the cell.

PMID- 9143275
TI  - Characterization of a DNA topoisomerase encoded by Amsacta moore entomopoxvirus.
AB  - We have identified an Amsacta moorei entomopoxvirus (AmEPV) gene encoding a DNA
      topoisomerase. The 333-amino acid AmEPV topoisomerase displays instructive
      sequence similarities to the previously identified topoisomerases encoded by five
      genera of vertebrate poxviruses. One hundred nine amino acids are identical or
      conserved among the six proteins. The gene encoding AmEPV topoisomerase was
      expressed in bacteria and the recombinant enzyme was partially purified. AmEPV
      topoisomerase is a monomeric enzyme that catalyzes the relaxation of supercoiled
      DNA. Like the vaccinia, Shope fibroma virus, and Orf virus enzymes, the AmEPV
      topoisomerase forms a covalent adduct with duplex DNA at the target sequence
      CCCTT decreases. The kinetic and equilibrium parameters of the DNA cleavage
      reaction of AmEPV topoisomerase (Kobs = 0.08 sec-1; Kcl = 0.22) are similar to
      those of the vaccinia virus enzyme.

PMID- 9143276
TI  - The complete DNA sequence of lymphocystis disease virus.
AB  - Lymphocystis disease virus (LCDV) is the causative agent of lymphocystis disease,
      which has been reported to occur in over 100 different fish species worldwide.
      LCDV is a member of the family Iridoviridae and the type species of the genus
      Lymphocystivirus. The virions contain a single linear double-stranded DNA
      molecule, which is circularly permuted, terminally redundant, and heavily
      methylated at cytosines in CpG sequences. The complete nucleotide sequence of
      LCDV-1 (flounder isolate) was determined by automated cycle sequencing and primer
      walking. The genome of LCDV-1 is 102.653 bp in length and contains 195 open
      reading frames with coding capacities ranging from 40 to 1199 amino acids.
      Computer-assisted analyses of the deduced amino acid sequences led to the
      identification of several putative gene products with significant homologies to
      entries in protein data banks, such as the two major subunits of the viral DNA
      dependent RNA polymerase, DNA polymerase, several protein kinases, two subunits
      of the ribonucleoside diphosphate reductase, DNA methyltransferase, the viral
      major capsid protein, insulin-like growth factor, and tumor necrosis factor
      receptor homolog.

PMID- 9143278
TI  - Down-regulation of groundnut rosette virus replication by a variant satellite
      RNA.
AB  - Symptom production in groundnut plants infected with groundnut rosette virus
      (GRV) depends on the presence of satellite RNA (sat-RNA) in the GRV culture, and
      sat-RNA variants that induce only mild symptoms are known. One such variant
      drastically diminished the replication of GRV genomic RNA in infected Nicotiana
      benthamiana plants. This down-regulating ability did not involve either of the
      two open reading frames in the sat-RNA but was controlled by a region near its 5'
      end, which is required for sat-RNA replication. When N. benthamiana plants were
      inoculated with GRV and the mild satellite and challenged by inoculation with a
      GRV isolate (YB) containing a sat-RNA that induces yellow blotch symptoms, no
      symptoms appeared and little GRV genomic RNA or sat-RNA was detected in the
      plants, provided the two inoculations were no more than 2 days apart. A GRV
      isolate containing a sat-RNA that neither induces symptoms in N. benthamiana nor
      affects genomic RNA accumulation also provided protection against yellow blotch
      symptom production if inoculated before or up to 2 days after isolate YB.
      However, in this case protection ws incomplete and both GRV RNA and sat-RNA
      accumulated to normal levels. It is suggested that sequences from the mild sat
      RNA may provide a novel source of resistance against rosette disease.

PMID- 9143277
TI  - Evidence that hepatitis C virus resistance to interferon is mediated through
      repression of the PKR protein kinase by the nonstructural 5A protein.
AB  - Hepatitis C virus (HCV) is the major cause of non-A non-B hepatitis and a leading
      cause of liver dysfunction worldwide. While the current therapy for chronic HCV
      infection is parenteral administration of type 1 interferon (IFN), only a
      fraction of HCV-infected individuals completely respond to treatment. Previous
      studies have correlated the IFN sensitivity of strain HCV-1b with mutations
      within a discrete region of the viral nonstructural 5A protein (NS5A), termed the
      interferon sensitivity determining region (ISDR), suggesting that NS5A may
      contribute to the IFN-resistant phenotype of HCV. To determine the importance of
      HCV NS5A and the NS5A ISDR in mediating HCV IFN resistance, we tested whether the
      NS5A protein could regulate the IFN-induced protein kinase, PKR, a mediator of
      IFN-induced antiviral resistance and a target of viral and cellular inhibitors.
      Using multiple approaches, including biochemical, transfection, and yeast
      genetics analyses, we can now report that NS5A represses PKR through a direct
      interaction with the protein kinase catalytic domain and that both PKR repression
      and interaction requires the ISDR. Thus, inactivation of PKR may be one mechanism
      by which HCV avoids the antiviral effects of IFN. Finally the inhibition of the
      PKR protein kinase, by NS5A is the first described function for this HCV protein.

PMID- 9143279
TI  - Infection and replication of herpes simplex virus type 1 in an organotypic
      epithelial culture system.
AB  - We have used the organotypic culture system as a model to study the initial
      infectious process and spread of herpes simplex virus type 1 (HSV-1) in fully
      stratified and differentiated human epithelial tissue. The growth kinetics of HSV
      1 were determined in organotypic tissues of human epidermal or ectocervical
      origin. Concurrently, we followed the spread of HSV-1 by immunostaining thin
      sections of infected organotypic tissue. After HSV-1 was applied to the top
      cornified epithelial layer, virus penetrated to the basal layer of replicating
      epithelium and grew to high titers. The virus was limited in its spread in that
      not all cells within the tissue had demonstrable infection. A ribonucleotide
      reductase mutant, ICP6 delta, could infect and replicate in basal layers of the
      organotypic tissues. However, we found that spread was limited in, and to, the
      basal cell layer. Peak ICP6 delta titers were 100-fold less than in cultures
      infected with wild-type HSV-1. Studies of HSV mutants should allow us to further
      define the role of specific viral genes which are associated with infection and
      spread in a tissue culture system that mimics the initial portal of entry for
      certain HSV infections.

PMID- 9143280
TI  - Origins of dengue type 2 viruses associated with increased pathogenicity in the
      Americas.
AB  - The recent emergence and spread of dengue hemorrhagic fever in the Americas have
      been a major source of concern. Efforts to control this disease are dependent on
      understanding the pathogenicity of dengue viruses and their transmission
      dynamics. Pathogenicity studies have been hampered by the lack of in vitro or in
      vivo models of severe dengue disease. Alternatively, molecular epidemiologic
      studies which associate certain dengue virus genetic types with severe dengue
      outbreaks may point to strains with increased pathogenicity. The comparison of
      nucleotide sequences (240 bp) from the E/NS1 gene region of the dengue virus
      genome has been shown to reflect evolutionary relationships and geographic
      origins of dengue virus strains. This approach was used to demonstrate an
      association between the introduction of two distinct genotypes of dengue type 2
      virus and the appearance of dengue hemorrhagic fever in the Americas.
      Phylogenetic analyses suggest that these genotypes originated in Southeast Asia
      and that they displaced the native, American genotype in at least four countries.
      Vaccination and other control efforts should therefore be directed at decreasing
      the transmission of these "virulent" genotypes.

PMID- 9143281
TI  - A BIR motif containing gene of African swine fever virus, 4CL, is nonessential
      for growth in vitro and viral virulence.
AB  - An African swine fever virus (ASFV) gene with similarity to viral and cellular
      inhibitor of apoptosis genes (iap) has been described in the African isolate
      Malawi Lil-20/1 (ORF 4CL) and a cell-culture-adapted European virus, BA71V (ORF
      A224L). The similarity of the ASFV gene to genes involved in inhibiting cellular
      apoptosis suggested the gene may regulate apoptosis in ASFV-infected cells and
      thus may function in ASFV virulence and/or host range. Sequence analysis of
      additional African and European pathogenic isolates demonstrates that this gene
      is highly conserved among both pig and tick ASFV isolates and that its similarity
      to iap genes is limited to the presence of a single IAP repeat motif (BIR motif)
      in the ASFV gene. To study gene function, a 4CL gene deletion mutant, delta 4CL,
      was constructed from the pathogenic Malawi Lil-20/1 isolate. Growth
      characteristics of delta 4CL in swine macrophage cell cultures were
      indistinguishable from those of parental virus. Infected macrophage survival time
      and the induction and magnitude of apoptosis in virus-infected macrophages were
      comparable for cells infected with either delta 4CL or parental virus. In
      infected swine, delta 4CL exhibited an unaltered Malawi Lil-20/1 virulence
      phenotype. These data indicate that, although highly conserved among ASFV
      isolates, the 4CL gene is nonessential for growth in macrophage cell cultures in
      vitro and for pig virulence. Additionally, despite its limited similarity to JAP
      genes, 4CL exhibits no anti-apoptotic function in infected macrophage cell
      cultures. The high degree of gene conservation among ASFV isolates, together with
      the apparent lack of function in the swine host, suggests 4CL may be a host range
      gene involved in aspects of infection in the arthropod host, ticks of the genus
      Ornithodoros.

PMID- 9143282
TI  - Screening of HIV-1 Env glycoproteins for the ability to raise neutralizing
      antibody using DNA immunization and recombinant vaccinia virus boosting.
AB  - HIV-1 envelopes from two series of primary isolates (from Swedish patients 5 and
      6), from JR-FL and BaL (prototypic monocyte/macrophage tropic viruses) and from
      HXB-2 (a prototypic T-cell-line-adapted virus), have been screened for their
      ability to elicit neutralizing antibody to HIV-1. Rabbits were primed by gene gun
      inoculation with plasmids expressing secreted monomeric (gp120) and oligomeric
      (gp140) forms of each Env. After four to six DNA immunizations administered over
      a 1-year period, rabbits were boosted with 10(8) plaque-forming units of a
      mixture of seven recombinant vaccinia viruses which express chimeric gp140 Envs
      (primary clade B sequences in a IIIb-related BH10 backbone). Neutralizing
      antibodies were assayed against two T-cell-line-adapted viruses (MN and IIIb),
      two non-syncytium-inducing (NSI) and two syncytium-inducing (SI) primary
      isolates, and two HIV-1-NL4-3-recombinants with patients 5 or 6 Envs (NL4-3/5A,
      NL4-3/6C). The DNA priming and recombinant vaccinia virus boosting raised low
      titers of neutralizing antibody in 10 of 19 rabbits. The highest titers of
      neutralizing activity (approximately 1:150 for MN) were raised in rabbits DNA
      primed with Envs from Swedish patients 5. These sera cross neutralized IIIb and
      MN but did not neutralize the primary isolates or the NL4-3 recombinant with the
      homologous 5A Env. Sera from rabbits primed with the HXB-2 Env DNA were, for the
      most part, type-specific for neutralization of IIIb. In one of three assays, sera
      from rabbits primed with plasmids expressing the JR-FL and BaL had possible low
      titer neutralizing activity for two NSI, but not two SI, primary isolates. Our
      results highlight the low immunogenic potential of the HIV-1 Env and demonstrate
      that different Envs have different potentials to raise low titer neutralizing
      antibody.

PMID- 9143283
TI  - Control of equine infectious anemia virus is not dependent on ADCC mediating
      antibodies.
AB  - Horses infected with equine infectious anemia virus (EIAV) have recurrent
      episodes of viremia which are eventually controlled, but the immune mechanisms
      have not been identified. Antibodies were detected to the surface of EIAV
      infected cells within 1 month postinfection and remained for at least 3.5 years
      postinfection. These antibodies recognized cell surface-exposed envelope (Env)
      glycoproteins, but could not mediate antibody dependent cellular cytotoxicity
      (ADCC) using EIAV-WSU5-infected equine kidney (EK) cells as targets and
      peripheral blood mononuclear cells (PBMC) or polymorphonuclear cells (PMN) as
      effector cells. Furthermore, purified IgG antibodies from horses infected with
      either EIAV-WSU5 or EIAV-Wyo did not mediate ADCC of infected target cells. Armed
      effector cells could not be detected in infected horse blood nor could effector
      cells be prearmed by incubation with serum antibodies to cell surface antigens.
      The use of EIAV-WSU5-infected equine macrophages as target cells did not result
      in ADCC. In contrast, serum antibody from EHV-1 vaccinated horses and PBMC or PMN
      as effector cells caused ADCC of EHV-1-infected EK cells. These results indicate
      that ADCC is not involved in the control of EIAV in carrier horses.

PMID- 9143284
TI  - Spontaneous occurrence of early region 1A reiteration mutants of type 5
      adenovirus in persistently infected human T-lymphocytes.
AB  - Mutants of type 5 adenovirus (Ad5) with reiterated DNA sequences in the E1a
      region appeared in a human T-lymphocyte cell line, Molt-4, persistently infected
      with H5sub304, a deletion/substitution mutant that has a wild-type phenotype in
      viral replication. Endonuclease analyses and DNA sequencing revealed DNA
      reiteration in each mutant. In the four representative mutants investigated, the
      DNA reiterations all started within a six-base-pair consensus sequence, G(or
      C)CTGTG, located in the second exon of the E1a region (at nt 1333, 1367, or
      1419). There was not any DNA homology between the breakpoints in the second exon
      and the inserting sequences (starting at nt 532, 710, or 792). Northern analyses
      suggested that the reiterated splicing sites of the representative mutants were
      all used in RNA splicing, and the closest donor and recipient joints were used
      most frequently. These observations imply that during persistent infection Ad5
      underwent spontaneous mutations by sequence-specific breakage and nonhomologous
      end-end joining recombination events. These E1a reiteration mutants could be
      propagated in HeLa, A549, and KB cells; they were genetically stable; and they
      killed CREF cells at a strikingly high frequency. Preliminary observations tend
      to correlate this CREF cell killing with the accumulation of the early viral
      proteins and/or viral DNA in the infected cells. This degree of cell damage was
      not observed in Ad5wt or H5sub304 infection of CREF cells. The observed E1a
      reiterations provide a model to gain insight into understanding the evolutionary
      events of some, if not all, adenovirus types during many years of symbiotic,
      persistent relationship in human tonsils and adenoids and possibly other lymphoid
      organs.

PMID- 9143285
TI  - The two P2 Ogr-like domains of the delta protein from bacteriophage P4 are
      required for activity.
AB  - The satellite P4 phage Delta protein positively regulates the late genes of its
      helper bacteriophage P2, as well as its own late genes. Delta is a member of a
      class of activators associated with P2-or P4-like phages and is the largest
      member of this family. It resembles a covalently joined head-to-tail dimer of the
      other members of this family of activators. We have analyzed the requirement for
      both standard domains of Delta through the isolation of amber mutants and the
      insertion of amber linkers. We show that both domains of Delta are required for
      DNA binding in vivo and for transcriptional activity. Proper spacing between the
      two domains is important for activity at two of the four P2 promoters. Expression
      of both domains from different plasmids causes activation of late gene
      transcription in vivo of all six late promoters of P2 and P4. A monomric Delta
      from another satellite phage, phi R73, can function efficiently as a covalent
      dimer but when this Delta is made dimeric with the second half of P4 delta, it
      activates less efficiently.

PMID- 9143286
TI  - Construction of infectious cDNA clones for dengue 2 virus: strain 16681 and its
      attenuated vaccine derivative, strain PDK-53.
AB  - We identified nine nucleotide differences between the genomes of dengue-2 (DEN-2)
      16681 virus and its vaccine derivative, strain PDK-53. These included a C-to-T
      (16681-to-PDK-53) mutation at nucleotide position 57 of the 5'-untranslated
      region, three silent mutations, and substitutions prM-29 Asp to Val, NS1-53 Gly
      to Asp, NS2A-181 Leu to Phe, NS3-250 Glu to Val, and NS4A-75 Gly to Ala.
      Unpassaged PDK-53 vaccine contained two genetic variants as a result of partial
      mutation at NS3-250. We constructed infectious cDNA clones for 16681 virus and
      each of the two PDK-53 variants. DEN-2 16681 clone-derived viruses were identical
      to the 16681 virus in plaque size and replication in LLC-MK2 cells, replication
      in C6/36 cells, E and prM epitopes, and neurovirulence for suckling mice. PDK-53
      virus and both clone-derived PDK-53 variants were attenuated in mice. However,
      the variant containing NS3-250-Glu was less temperature sensitive and replicated
      better in C6/36 cells than did PDK-53 virus. The variant containing NS3-250-Val
      had smaller, more diffuse plaques, decreased replication, and increased
      temperature sensitivity in LLC-MK2 cells relative to PDK-53 virus. Both PDK-53
      virus and the NS3-250-Val variant replicated poorly in C6/36 cells relative to
      16681 virus. Unpassaged PDK-53 vaccine virus and the virus passaged once in LLC
      MK2 cells had genomes of identical sequence, including the mixed NS3-250-Glu/Val
      locus. Although the NS3-250-Val mutation clearly affected virus replication in
      vitro, it was not a major determinant of attenuation for PDK-53 virus in suckling
      mice.

PMID- 9143287
TI  - Efficient autoproteolytic processing of the MHV-A59 3C-like proteinase from the
      flanking hydrophobic domains requires membranes.
AB  - The replicase gene of the coronavirus MHV-A59 encodes a serine-like proteinase
      similar to the 3C proteinases of picornaviruses. This proteinase domain is
      flanked on both sides by hydrophobic, potentially membrane-spanning, regions.
      Cell-free expression of a plasmid encoding only the 3C-like proteinase (3CLpro)
      resulted in the synthesis of a 29-kDa protein that was specifically recognized by
      an antibody directed against the carboxy-terminal region of the proteinase. A
      protein of identical mobility was detected in MHV-A59-infected cell lysates. In
      vitro expression of a plasmid encoding the 3CLpro and portions of the two
      flanking hydrophobic regions resulted in inefficient processing of the 29-kDa
      protein. However, the efficiency of this processing event was enhanced by the
      addition of canine pancreatic microsomes to the translation reaction, or removal
      of one of the flanking hydrophobic domains. Proteolysis was inhibited in the
      presence of N-ethylmaleimide (NEM) or by mutagenesis of the catalytic cysteine
      residue of the proteinase, indicating that the 3CLpro is responsible for its
      autoproteolytic cleavage from the flanking domains. Microsomal membranes were
      unable to enhance the trans processing of a precursor containing the inactive
      proteinase domain and both hydrophobic regions by a recombinant 3CLpro expressed
      from Escherichia coli. Membrane association assays demonstrated that the 29-kDa
      3CLpro was present in the soluble fraction of the reticulocyte lysates, while
      polypeptides containing the hydrophobic domains associated with the membrane
      pelletes. With the help of a viral epitope tag, we identified a 22-kDa membrane
      associated polypeptide as the proteolytic product containing the amino-terminal
      hydrophobic domain.

PMID- 9143288
TI  - Effects of mutations in the beet western yellows virus readthrough protein on its
      expression and packaging and on virus accumulation, symptoms, and aphid
      transmission.
AB  - Virions of beet western yellows luteovirus contain a major capsid protein (P22.5)
      and a minor readthrough protein (P74), produced by translational readthrough of
      the major capsid protein sequence into the neighboring open reading frame, which
      encodes the readthrough domain (RTD). The RTD contains determinants required for
      efficient virus accumulation in agroinfected plants and for aphid transmission.
      The C-terminal halves of the RTD are not well conserved among luteoviruses but
      the N-terminal halves contain many conserved sequence motifs, including a proline
      rich sequence separating the rest of the RTD from the sequence corresponding to
      the major coat protein. To map different biological functions to these regions,
      short in-frame deletions were introduced at different sites in the RTD and the
      mutant genomes were transmitted to protoplasts as transcripts and to Nicotiana
      clevelandii by agroinfection. Deletions in the nonconserved portion of the RTD
      did not block aphid transmission but had a moderate inhibitory effect on virus
      accumulation in plants and abolished symptoms. Deletion of the proline tract and
      the junction between the conserved and nonconserved regions inhibited readthrough
      protein accumulation in protoplasts by at least 10-fold. The mutants accumulated
      small amounts of virus in plants, did not induce symptoms, and were
      nontransmissible by aphids using agroinfected plants, extracts of infected
      protoplasts, or purified virus as a source of inoculum. Other deletions in the
      conserved portion of the RTD did not markedly diminish readthrough protein
      accumulation but abolished its incorporation into virions. These mutants
      accumulated to low levels in agroinfected plants and elicited symptoms, but could
      not be aphid-transmitted. A preliminary map has been produced mapping these
      functions to different parts of the RTD.

PMID- 9143289
TI  - Determinants of mouse hepatitis virus 3C-like proteinase activity.
AB  - The coronavirus, mouse hepatitis virus strain A59 (MHV), expresses a chymotrypsin
      like cysteine proteinase (3CLpro) within the gene 1 polyprotein. The MHV 3CLpro
      is similar to the picornavirus 3C proteinases in the relative location of
      confirmed catalytic histidine and cysteine residues and in the predicted use of
      Q/(S, A, G) dipeptide cleavage sites. However, less is known concerning the
      participation of aspartic acid or glutamic acid residues in catalysis by the
      coronavirus 3C-like proteinases or of the precise coding sequence of 3CLpro
      within the gene 1 polyprotein. In this study, aspartic acid residues in MHV
      3CLpro were mutated and the mutant proteinases were tested for activity in an in
      vitro trans cleavage assay. MHV 3CLpro was not inactivated by substitutions at
      Asp3386 (D53) or Asp3398 (D65), demonstrating that they were not catalytic
      residues. MHV 3CLpro was able to cleave at a glutamine-glycine (QG3607-8)
      dipeptide within the 3CLpro domain upstream from the predicted carboxy-terminal
      QS3636-6 cleavage site of 3CLpro. The predicted full-length 3CLpro (S3334 to
      Q3635) had an apparent mass of 27 kDa, identical to the p27 3CLpro in cells,
      whereas the truncated proteinase (S3334 to Q3607) had an apparent mass of 24 kDa.
      This 28-amino-acid carboxy-terminal truncation of 3CLpro rendered it inactive in
      a trans cleavage assay. Thus, MHV 3CLpro was able to cleave at a site within the
      putative full-length proteinase, but the entire predicted 3CLpro domain was
      required for activity. These studies suggest that the coronavirus 3CL-proteinases
      may have a substantially different structure and catalytic mechanism that other
      3C-like proteinases.

PMID- 9143290
TI  - Characterization of cucumber mosaic virus. III. Localization of sequences in the
      movement protein controlling systemic infection in cucurbits.
AB  - Cucumber mosaic virus (CMV), generated from biologically active cDNA clones of
      Fny-CMV RNA 1 plus 2 and Sny-CMV RNA 3, derived from the Fny- and Sny-strains of
      CMV, was able to infect tobacco but not squash plants systemically. In squash,
      viral RNA, movement protein, and coat protein all accumulated in the inoculated
      cotyledons. The lack of systemic infection was associated with a reduced rate of
      cell-to-cell movement within the cotyledons. The restricted movement mapped to
      two sequence changes in the codons of amino acids 51 and 240 of the Sny-CMV 3a
      gene. These same sequence changes previously were shown to be associated with
      high levels of 3a protein accumulation and chronic vs acute, cyclic infection
      typical of Sny-CMV vs Fny-CMV [Gal-on et al. (1996). Virology 226, 354-361]. Fny
      CMV, mutated in the codons of 3a gene amino acids 51 and 240, was still able to
      infect several solanaceous hosts (tobacco, tomato, and pepper) systemically, but
      did not elicit a typical CMV systemic infection on any of several cucurbit hosts
      (cucumber, melon, or squash). The significance of the location of amino acid
      positions 51 and 240 in the 3a movement protein is discussed.

PMID- 9143291
TI  - The location and sequence composition of the murine cytomegalovirus replicator
      (oriLyt).
AB  - DNA replication during human or simian cytomegalovirus (CMV) infection has been
      shown to be under control of a replicator region referred to as oriLyt. The
      murine CMV oriLyt has been mapped to a region of the genome located upstream of
      the gene encoding the herpesvirus-conserved single-stranded DNA binding protein,
      analogous to human and simian CMV oriLyts. A minimal oriLyt of approximately 1.7
      kbp has been identified using a transient replication system. Like occurs with
      human and simian CMV counterparts, addition of flanking sequences to this minimal
      origin-stimulated replication efficiency. Analysis of the DNA sequence in this
      region shows that murine CMV oriLyt is complex and exhibits an asymmetric
      distribution of nucleotides as well as many repeat sequence elements, including
      distinct AT- and GC-rich regions and region with arrays of closely spaced direct
      repeats. Despite similarities in organization of all three CMV oriLyts, no
      sequence identity and only limited DNA sequence similarity was detectable.
      Consistent with this sequence divergence, the human and murine CMV oriLyts were
      unable to substitute for one another in transient replication assays.

PMID- 9143292
TI  - Alternative expression of a chitosanase gene produces two different proteins in
      cells infected with Chlorella virus CVK2.
AB  - Several Chlorella virus CVK2 proteins had chitosanase and/or chitinase
      activities. A gene coding for an ORF of 328 amino acids (aa) with a predicted
      molecular mass of 36,769 Da was cloned from the viral genome. The predicted amino
      acid sequence of an N'-portion (174 aa) of this gene product (vChta-1) showed 22
      to 25% identity with various bacterial chitosanases. A glutathione S-transferase
      (GST)-vChta-1 fusion protein had strong chitosanase activity. Western blot
      analysis with antisera raised against the vChta-1 protein identified two proteins
      of 37 and 65 kDa in virus-infected Chlorella cells beginning at 240 min
      postinfection and continuing until cell lysis. The larger protein was packaged in
      the virion, while the smaller one remained in the cell lysate. Both chitosanase
      proteins were produced from the single gene, vChta-1, by a mechanism of
      alternative gene expression.

PMID- 9143293
TI  - Structural and antigenic identification of the ORF12 protein (alpha TIF) of
      equine herpesvirus 1.
AB  - The equine herpesvirus 1 (EHV-1) homolog of the herpes simplex virus type 1 (HSV
      1) tegument phosphoprotein, alpha TIF (Vmw65; VP16), was identified previously as
      the product of open reading frame 12 (ORF12) and shown to transactivate immediate
      early (IE) gene promoters. However, a specific virion protein corresponding to
      the ORF12 product has not been identified definitively. In the present study the
      ORF12 protein, designated ETIF, was identified as a 60-kDa virion component on
      the basis of protein fingerprint analyses in which the limited proteolysis
      profiles of the major 60-kDa in vitro transcription/ translation product of an
      ORF12 expression vector (pT7-12) were compared to those of purified virion
      proteins of similar size. ETIF was localized to the viral tegument in Western
      blot assays of EHV-1 virions and subvirion fractions using polyclonal antiserum
      and monoclonal antibodies generated against a glutathione-S-transferase-ETIF
      fusion protein. Northern and Western blot analyses of EHV-1-infected cell lysates
      prepared under various metabolic blocks indicated that ORF12 is expressed as a
      late gene, and cross reaction of polyclonal anti-GST-ETIF with a 63.5-kDa HSV-1
      protein species suggested that ETIF and HSV-1 alpha TIF are antigenically
      related. Last, DNA band shift assays used to assess ETIF-specific complex
      formation indicated that ETIF participates in an infected cell protein complex
      with the EHV-1 IE promoter TAATGARAT motif.

PMID- 9143294
TI  - Antigenic variants of yellow fever virus with an altered neurovirulence phenotype
      in mice.
AB  - The live-attenuated yellow fever (YF) vaccine virus, strain 17D-204, has long
      been known to consist of a heterologous population of virions. Gould et al. (J.
      Gen. Virol. 70, 1889-1894 (1989)) previously demonstrated that variant viruses
      exhibiting a YF wild-type-specific envelope (E) protein epitope are present at
      low frequency in the vaccine pool and were able to isolate representative virus
      variants with and without this epitope, designated 17D(+wt) and 17D(-wt),
      respectively. These variants were employed here in an investigation of YF virus
      pathogenesis in the mouse model. Both the 17D-204 parent and the 17D(+wt) variant
      viruses were lethal for adult outbred mice by the intracerebral route of
      inoculation. However, the 17D(-wt) variant was significantly attenuated (18%
      mortality rate) and replicated to much lower titer in the brains of infected
      mice. A single amino acid substitution in the envelope (E) protein at E-240 (Ala-
      >Val) was identified as responsible for the restricted replication of the 17D(
      wt) variant in vivo. The 17D(+wt) variant has an additional second-site mutation,
      believed to encode a reversion to the neurovirulence phenotype of the 17D-204
      parent virus. The amino acid substitution in the E protein at E-173 (Thr-->Ile)
      of the 17D(+wt) variant which results in the appearance of the wild-type-specific
      epitope or nucleotide changes in the 5' and 3' noncoding regions of the virus are
      proposed as a candidates.

PMID- 9143295
TI  - Upstream stimulatory factor family binds to the herpes simplex virus type 1
      latency-associated transcript promoter.
AB  - The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT)
      promoter 1 (LP1) is the only viral promoter that exhibits detectable
      transcriptional activity during a latent HSV infection. The LAT promoter-binding
      factor (LPBF) regulatory sequence (nucleotides -65 to -72 relative to the
      transcriptional start site of the 8.3-kb primary transcript) closely resembles
      the core recognition sequence required for binding members of the upstream
      stimulatory factor (USF)/major late transcription factor (MLTF) family. In this
      analysis, we demonstrate that oligonucleotides containing either the LPBF
      recognition sequence or the USF/MLTF recognition sequences from previously
      described promoters bind cellular factors which exhibit very similar mobilities
      in electrophoretic mobility shift (EMS) analyses. We also observe a high degree
      of similarity in competition profiles obtained in competition EMS analyses
      utilizing oligonucleotides containing recognition sequences for either LPBF or
      USF/MLTF. Furthermore, antibody supershift EMS analyses have demonstrated that
      the factors binding the LPBF or USF/MLTF recognition sites in these
      oligonucleotides are antigenically related, if not identical, and that greater
      than 90% of the LPBF-binding activity is antigenically related to USF. In
      addition, we demonstrate that both forms of in vitro translated USF proteins (43
      and 44 kDa) bind to the LPBF recognition sequence within HSV-1 LP1. Taken
      together, these data indicate that USF is capable of binding to the HSV-1 LPBF
      recognition sequence and that USF is a major LPBF-binding activity in cells of
      neuronal and nonneuronal lineage. These data further support the hypothesis that
      USF may indeed play a significant role in the transcriptional activity of HSV-1
      LP1.

PMID- 9143296
TI  - Human immunodeficiency virus type 1 (HIV-1) infection of herpesvirus saimiri
      immortalized human CD4-positive T lymphoblastoid cells: evidence of enhanced HIV
      1 replication and cytopathic effects caused by endogenous interferon-gamma.
AB  - Herpesvirus saimiri (HVS) is a nonhuman primate gamma herpesvirus which can
      immortalize human T lymphocytes similar to Epstein-Barr virus immortalization of
      B cells. The HVS-immortalized T cell lines can be cloned and they remain
      functional, including susceptibility of CD4 expressing T cells to infection with
      human immunodeficiency virus type 1 (HIV-1). In this report, we have used five
      such HVS-transformed CD4-positive T cell clones to reevaluate the role of
      endogenous interferon gamma (IFN gamma) in HIV-1 replication in T cells. All five
      clones had similar phenotypes; and four clones constitutively produced IFN gamma
      and one clone did not. All five clones could be efficiently infected with HIV-1.
      HIV-1 infection of the IFN gamma-positive cells also upregulated IFN gamma mRNA
      production and IFN gamma secretion but not production of IL-2 or IL-4. In
      contrast, infection of IFN gamma-negative cells did not induce IFN gamma, IL-2,
      or IL-4. Exposure to anti-IFN gamma antibodies after HIV-1 infection
      significantly reduced virus production and inhibited virus-induced death of IFN
      gamma-positive cells but had no effect on IFN gamma-negative cells. We conclude
      that in CD4-positive T lymphocytes immortalized by HVS endogenous IFN gamma does
      not inhibit HIV-1 but enhances HIV-1 replication and cytolysis. The potential
      augmenting effects of IFN gamma on HIV-1 replication in CD4-positive T cells
      recommend caution in a therapeutic use of this cytokine in AIDS.

PMID- 9143297
TI  - Enhancement of HIV-1-induced syncytium formation in T cells by the tyrosyl kinase
      p56lck.
AB  - The CD4 glycoprotein is the primary cellular receptor for human immunodeficiency
      virus type 1 (HIV-1) and has also been reported to be physically associated with
      p56lck, a tyrosyl protein kinase p56lck is a member of the src family of
      nonreceptor protein-tyrosine kinases and is expressed predominantly in T
      lymphocytes. Our objective was to study the effect of p56lck on the biology of
      HIV-1. For this purpose, we have stably transfected two human p56lck negative T
      cell lines (C8166-45 and MT-2) with plasmids encoding for this cellular protein.
      Following coculture with HIV-1-infected cells or infection with cell-free virus,
      p56lck-expressing cell lines showed a greater propensity for virus-mediated
      syncytium formation than parental p56lck-negative cells. The enhancement of HIV-1
      induced syncytium formation was not associated with the kinase activity of
      p56lck, as demonstrated by experiments using a kinase-deficient mutant. However,
      the physical interaction between CD4 and p56lck was shown to be necessary to
      obtain the enhancement of syncytium formation since a mutated version of p56lck,
      which is deficient in its capacity to associate with CD4, did not lead to an
      increase in virus-mediated cell-to-cell fusion events. Finally, we determined
      that cells transfected with wild-type and kinase-negative mutant p56lck showed a
      reduced rate of CD4 endocytosis compared to parental p56lck-negative cells.
      Together, these results suggest that p56lck can be seen as an accessory molecule
      facilitating HIV-1-mediated syncytium formation in T cells by a mechanism
      involving the stabilization of the CD4 molecule at the cell surface.

PMID- 9143298
TI  - An equine herpesvirus-1 gene 71 deletant is attenuated and elicits a protective
      immune response in mice.
AB  - The pathogenesis of pulmonary infection and the immune response following
      intranasal inoculation of mice with two equine herpesvirus type 1 (EHV-1)
      deletion mutants have been assessed. The mutants, ED71 and ED75, have deletions
      in genes 71 (EUS4) and 75 (10K), respectively. Deletions were replaced by the
      Escherichia coli lacZ gene driven by the simian virus 40 (SV40) early promoter.
      It has previously been shown that the protein products of genes 71 and 75 are
      dispensable in vitro but that removal of gene 71 results in a defect in virus
      maturation and capsid envelopment which impairs the ability of mutant virus to
      spread via release and readsorption. This study demonstrated that the 192-kDa
      gene 71 product is required for full expression of virulence in mice, whereas the
      putative 10-kDa product of gene 75 has minimal effect. Both mutants exhibited the
      same tissue and cytotropism as wild-type EHV-1 and induced both humoral and cell
      mediated immune responses indistinguishable from those induced by the parental
      strain. Irrespective of the reduced pathogenicity of the gene 71 mutant, infected
      mice were protected against a challenge with wild-type EHV-1. These findings
      highlight the potential of ED71 as a vaccine candidate.

PMID- 9143299
TI  - The virion host shutoff function of herpes simplex virus type 1 plays a role in
      corneal invasion and functions independently of the cell cycle.
AB  - A significant restriction was demonstrated in the ability of herpes simplex virus
      type 1 virion host shutoff (vhs) mutant viruses to invade the corneal epithelium.
      Viral replication and invasion was confined to the areas of the cornea which were
      scarified prior to infection. Differences between wild-type and vhs mutant
      replication in corneas in vivo were 100- to 1000-fold at all timepoints
      postinfection. Smaller but still significant growth restrictions were observed in
      cultured corneal cells. This difference between in vitro and in vivo is not
      likely to be due to differences in cell cycle status since vhs-induced RNA
      degradation can occur in both cycling and noncycling cells in vitro. The vhs
      function is therefore important for invasion of the cornea and secondarily the
      nervous system and is thereby required for efficient establishment of latency.

PMID- 9143300
TI  - Mutations in the region encoding the central domain of helper component
      proteinase (HC-Pro) eliminate potato virus X/potyviral synergism.
AB  - Coinfection of tobacco plants with potato virus X (PVX) and any of several
      members of the potyvirus group causes a synergistic disease characterized by a
      dramatic increase in symptom severity correlated with a 3- to 10-fold increase in
      the accumulation of PVX in the first systemically infected leaves. We have
      recently shown that PVX/potyviral synergistic disease is mediated by expression
      of potyviral 5'-proximal sequences encoding P1, helper component-proteinase (HC
      Pro), and a fraction of P3 (termed P1/HC-Pro sequence). Here we report the effect
      of mutations in this potyviral sequence on the induction of synergistic disease.
      Three transgenic tobacco lines expressing the tobacco etch potyvirus (TEV) P1/HC
      Pro sequence with mutations within the P1 coding region were not impaired in
      their ability to mediate synergism when infected with PVX. In contrast, two of
      three transgenic lines with mutations in the HC-Pro coding region were unable to
      induce the synergistic increases in either symptom severity or PVX accumulation.
      Loss of synergistic function was associated with mutations within the region
      encoding the central domain of HC-Pro, while the ability to induce synergism was
      retained in a transgenic line expressing HC-Pro with an alteration in the amino
      terminal "zinc-finger domain." In coinoculation experiments, a TEV mutant lacking
      the sequence encoding the zinc-linger domain of HC-Pro induced a typical
      synergistic response in interaction with PVX. The results indicate that the zinc
      finger domain comprising the first 66 amino acid residues of HC-Pro is
      dispensable for induction of synergistic disease and transactivation of PVX
      multiplication, while regions within the central domain of HC-Pro are essential
      for both of these responses.

PMID- 9143301
TI  - Sequence analysis of HIV-1 group O from Norwegian patients infected in the 1960s.
AB  - Three Norwegians, a couple and their daughter, died from AIDS in 1976 after up to
      10 years of clinical manifestations of HIV infection (Lindboe et al., 1986, Acta
      Pathol. Microbiol, Immunol. Scand. 94, 117-123; Froland et al., 1988, Lancet i,
      1344-1345). We here demonstrate the presence of HIV DNA in autopsy materials from
      the father and the daughter. In phylogenetic analysis, the obtained sequences of
      the HIV pol and vif genes clustered with the HIV-1 group O clade. The genotyping
      was confirmed by detection of antibodies against HIV-1 group O in blood samples
      from the father and the mother. That these and other early isolates of HIV-1 are
      very similar to the presently circulating viruses and not intermediates between
      the present subtypes, verifies that the latest common ancestor of HIV-1 existed
      long before the emergence of the present epidemic. The presence of HIV-1 group O
      30 years ago suggests that the limited spread of these viruses, compared to HIV-1
      group M viruses, is not due to a later emergence of the group O viruses.

PMID- 9143302
TI  - Antigenically distinct G glycoproteins of BRSV strains share a high degree of
      genetic homogeneity.
AB  - Bovine respiratory syncytial (BRS) virus can be divided into antigenic subgroups
      based on the reactivity of monoclonal antibodies (mAbs) to the attachment
      glycoprotein, G. Further, the polyclonal antibody response of calves vaccinated
      with recombinant vaccinia viruses expressing the G protein of a particular
      subgroup is also subgroup-specific. To investigate the genetic basis for the
      antigenic heterogeneity of the BRS virus G protein, the genes for the G protein
      from 6 BRS virus strains representative of the antigenic subgroups were cloned,
      sequenced, and compared with the prototype subgroup A strain, 391-2. There was
      only 10% nucleic acid difference and 15% amino acid difference between strains
      from different subgroups. These findings are in sharp contrast to the situation
      with human RS virus, where there is a 45% difference in amino acid identity
      between subgroups. In fact, the extent of amino acid difference between BRS virus
      subgroups is similar to the level of heterogeneity observed within human
      subgroups. Analysis of the reactivity of mAbs with peptides from the cysteine
      rich region (174-188) of the G protein representing each antigenic subgroup
      indicated that amino acids at positions 180, 183, and possibly 184 are important
      in subgroup distinction. Taken together, these data suggest that although the
      genetic variation responsible for the antigenic differences determining subgroups
      among BRS viruses is more limited than that observed among human RS virus
      subgroups, the amino acid differences that exist have a profound effect upon
      antibody recognition.

PMID- 9143303
TI  - Multiple mechanisms for the inhibition of entry and uncoating of superinfecting
      Semliki Forest virus.
AB  - Recombinant Semliki Forest viruses (SFV) that express one or none of the viral
      structural proteins were used to infect cells and to analyze the fate of incoming
      superinfecting wild-type viruses. It was found that in addition to the previously
      described block in replication that superinfecting viruses encounter within 15
      min of infection, other mechanisms of superinfection inhibition occurred at later
      times. Over a 6-hr infection period, inhibition was seen in binding of virus to
      the cell surface, in acid-activated penetration into the cytoplasm, and in
      uncoating of nucleocapsids. For each of these processes, the inhibitory mechanism
      was investigated. In summary, we found that infection evoked several independent
      mechanisms for blocking the entry and uncoating of superinfecting viruses. The
      results also offered new insights into the normal processes of penetration and
      uncoating of SFV.

PMID- 9143304
TI  - The human cytomegalovirus UL97 protein is phosphorylated and a component of
      virions.
AB  - The expression of the human cytomegalovirus (HCMV) UL97 open reading frame in
      infected or transfected cells in the presence of the antiherpes compound
      ganciclovir (GCV) results in the intracellular phosphorylation of GCV. There are
      conventional kinase domains within the UL97-encoded protein (pUL97). However, the
      role of pUL97 in the HCMV replication cycle, and the mechanism by which it causes
      phosphorylation of GCV, are currently unknown. Herein, the biosynthesis and
      biogenesis of pUL97 was studied in HCMV-infected cells. pUL97 is expressed with
      early-late kinetics and is posttranslationally modified by phosphorylation. This
      phosphorylation occurs within 1 hr after synthesis, affects the electrophoretic
      mobility of pUL97, and is independent of the presence of other HCMV proteins.
      pUL97 was localized to the nucleus of infected cells and found in the HCMV
      virions. Thus, pUL97 is a virion phosphoprotein, and a likely tegument component.

PMID- 9143305
TI  - The apoptosis pathway triggered by the interferon-induced protein kinase PKR
      requires the third basic domain, initiates upstream of Bcl-2, and involves ICE
      like proteases.
AB  - The interferon-induced double-stranded RNA-dependent protein kinase (PKR) is a
      serine/threonine kinase which exerts antiviral and anticellular functions. The
      antiviral effect of PKR is mediated by the phosphorylation of the alpha subunit
      of the translational initiation factor elF-2 alpha, while it is not known whether
      the anticellular effect is due to phosphorylation of elF-2 alpha, l kappa B, or
      other unknown substrates. We have previously shown that activation of PKR during
      infection of cells with a vaccinia virus recombinant expressing the wild-type
      kinase resulted in a complete inhibition of viral and cellular protein synthesis
      and in the induction of apoptosis. Here, we report that expression of the human
      proto-oncogene bcl-2 blocks PKR-induced apoptosis but not PKR-induced inhibition
      of translation. In addition, PKR-induced apoptosis resulted in a cleavage of the
      death substrate poly(ADP-ribose) polymerase (PARP). Moreover, induction of
      apoptosis by PKR was not observed with a mutant lacking the third basic region
      (aa 234-272). Taken together, these results suggest that the third basic region
      of PKR is required for PKR-induced apoptosis, the process is initiated upstream
      of bcl-2 and involves activation of a cellular protease, CPP32, or its family
      members that cleave PARP.

PMID- 9143306
TI  - Recombinant HIV envelope expressed in an alpha-glucosidase I-deficient CHO cell
      line and its parental cell line in the presence of 1-deoxynojirimycin is
      functional.
AB  - alpha-Glucosidase inhibitors-e.g., 1-deoxynojirimycin (DNM)-interfere with HIV
      infectivity in CD4+ cell cultures but have proven unsuccessful in clinical
      trials. In vitro, several HIV Env properties, including the cleavage of the Env
      precursor gp 160, the immunoreactivity of the third variable domain (V3) of Env,
      the binding to the CD4 receptor, and the induction of the membrane fusion between
      the virus and the host cell, have been reported to be altered by such inhibitors.
      We have studied these properties for Env expressed via a recombinant vaccinia
      virus in two Chinese hamster ovary cell lines, an alpha-glucosidase I-deficient
      cell line and its parental cell line, treated with DNM under conditions that have
      been reported to alter Env properties. The glycosylation of Env, but not the
      quantity produced, varied in accordance with the experimental conditions.
      However, irrespective of these conditions, Env cleavage, V3 immunoreactivity, CD4
      binding, membrane expression, and ability to induce syncytium formation were
      similar. Thus, neither the alpha-glucosidase I deficiency nor DNM treatment had a
      significant effect on the properties of Env produced here. Cellular mechanisms
      that may allow the normal expression of Env are discussed and may offer an
      explanation for the many discrepant results obtained to date on the effects of
      DNM on HIV Env.

PMID- 9143307
TI  - The tax gene sequences form two divergent monophyletic lineages corresponding to
      types I and II of simian and human T-cell leukemia/lymphotropic viruses.
AB  - Evolutionary associations of human and simian T-cell leukemia/lymphotropic
      viruses I and II (HTLV-I/II and STLV-I/II) are inferred from phylogenetic
      analysis of tax gene sequences. Samples studied consisted of a geographically
      diverse assemblage of viral strains obtained from 10 human subjects and 20
      individuals representing 12 species of nonhuman primates. Sequence analyses
      identified distinct substitutions, which distinguished between viral types I and
      II, irrespective of host species. Phylogenetic reconstruction of nucleotide
      sequences strongly supported two major evolutionary groups corresponding to viral
      types I and II. With the type I lineage, clusters were composed of strains from
      multiple host species. A genetically diverse, monophyletic lineage consisting of
      eight new viral strains from several species of Asian macaques was identified.
      The second lineage consisted of a monophyletic assemblage of HTLV-II/STLV-II
      strains from Africa and the New World, including an isolate from a pygmy chimp
      (Pan paniscus) as an early divergence within the lineage. High levels of genetic
      variation among strains from Asian STLV-I macaque suggest the virus arose in
      Asia. Evidence of the origin of the type II virus is less clear, but diversity
      among HTLV-II variants from a single isolated population of Mbati villagers is
      suggestive but not proof of an African origin.

PMID- 9143308
TI  - Role of the amino-terminal extracellular domain of CXCR-4 in human
      immunodeficiency virus type 1 entry.
AB  - We have studied the role of the N-terminal extracellular domain of the human
      immunodeficiency virus type 1 (HIV-1) coreceptor, CXCR-4, in the entry and fusion
      of syncytium-inducing strains of HIV-1. Progressive deletions were introduced in
      the N-terminal extracellular domain of CXCR-4 and the effect on infection by
      different isolates was tested. Infection of cells expressing the different CXCR-4
      deletion mutants by HIV-1 LAI and 89.6 was reduced only about twofold. In
      contrast, the HIV-1 GUN-1 and RF isolates were substantially more impaired in
      their ability to mediate cell-free infection and cell-cell fusion. Since LAI and
      RF are T-cell line-tropic viruses while 89.6 and GUN-1 are dual tropic, no clear
      correlation between tropism and requirements for CXCR-4 N-terminal sequences
      emerged. We also introduced point mutations at the two N-linked glycosylation
      sites. The isolates tested (LAI, RF, GUN-1, and 89.6) were not affected by the
      removal of predicted N-linked glycosylation sites in CXCR-4. We conclude that
      distinct virus strains interact differently with the CXCR-4 coreceptor and that
      the N-terminal extracellular domain is not the sole functional domain important
      for HIV-1 entry.

PMID- 9143309
TI  - In vitro selection for different mutational patterns in the HIV-1 reverse
      transcriptase using high and low selective pressure of the nonnucleoside reverse
      transcriptase inhibitor HBY 097.
AB  - In vitro resistance of HIV-1 against high levels of HBY 097 ((S)-4
      isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3, 4-dihydro-quinoxaline-2(1H)
      thione) and other quinoxaline nonnucleoside reverse transcriptase inhibitors
      (NNRTIs) is characterized by a specific amino acid substitution in the reverse
      transcriptase (RT), Gly 190Glu. This change results in decreased RT polymerase
      activity and in reduced growth properties of the corresponding viral variant.
      Here we show that the appearance of the crippling mutation at codon 190 can be
      prevented by lowering the selective pressure exerted by HBY 097. Under low
      selective pressure an accumulation of other NNRTI-specific mutations is observed.
      Up to five NNRTI-specific substitutions were detected in some of these virus
      lineages. In addition, we report novel RT amino acid changes which were not
      observed previously, including Val106lle, Val106Leu, and Gly190Thr. HBY 097
      selects for different mutational patterns under high and low selective pressure
      conditions, respectively. Thus, the type of mutations which appear in HIV
      infected patients undergoing therapy may be determined by the levels of the
      selecting drug.

PMID- 9143310
TI  - Delineation of regions important for heteromeric association of hepatitis C virus
      E1 and E2.
AB  - Hepatitis C virus (HCV) is the major causative agent of blood-borne non-A non-B
      hepatitis. The persistence of HCV infection is believed to reflect escape from
      the host immunosurveillance system by mutations in hypervariable region 1 (HVR1)
      of the envelope protein 2 (E2). Two envelope proteins of HCV, E1 and E2, have
      been reported to form a heteromeric complex but the exact organization of the
      viral envelope proteins remains uncertain. We examined the interaction of E1 and
      E2 by far- Western blotting using the bacterial recombinant proteins and also by
      pull-down assay using mammalian expressed proteins. The major E1-interacting site
      of E2 was mapped within the N-terminal part of E2 (NCD1) (aa 415 to 500 of the
      polyprotein). Both HVR1 and HVR2, located at the N-terminal part of E2, were
      dispensable for the interaction. Although several discontinuous regions within
      NCD1 seemed to contribute to the strong binding to E1, the highly conserved amino
      acid sequences flanking HVR2 had the most significant effect. The amino acid
      residues "WHY" from 489 to 491 of E2 played an especially crucial role since the
      constructs with the internal deletion or substitution of the residues showed
      severely impaired E1-binding. The N-terminal part of E1 is important for the E2
      binding as determined by far-Western blotting using the mammalian- and bacterial
      expressed E2 proteins as probes. The mammalian-expressed, glycosylated forms of
      the E1 and E2 proteins exhibited E1-E2 binding activities similar to those of the
      bacterial-expressed, nonglycosylated forms in pull-down assays, suggesting that
      glycosylation is not prerequisite for the heteromeric complex formation of E1 and
      E2.

PMID- 9143312
TI  - Repression of bax gene expression by the HTLV-1 Tax protein: implications for
      suppression of apoptosis in virally infected cells.
AB  - The human T-cell leukemia virus-encoded oncoprotein Tax is a potent deregulator
      of cellular gene expression. Here we report that Tax represses transcription of
      the human bax gene, a gene whose protein product accelerates apoptosis. This
      repression is mediated through a 27-bp sequence in the bax promoter that contains
      a putative basic helix-loop-helix binding site. Deletion of this sequence
      abolishes Tax-mediated repression of bax. Repression of the bax gene may be
      biologically significant, as we also show that HTLV-I-infected cell lines are
      resistant to a variety of physical, chemical, and biological stimuli which induce
      apoptosis in uninfected T-cells. The repression of genes involved in promoting
      apoptosis, including the bax gene, may contribute to retroviral survival, and
      initiate a pathway toward malignant transformation.

PMID- 9143311
TI  - CD4-independent infection by HIV-2 (ROD/B): use of the 7-transmembrane receptors
      CXCR-4, CCR-3, and V28 for entry.
AB  - We have assayed a variety of 7tm chemokine receptors (CCR-2b, CCR-3, CCR-4, CCR
      5, CXCR-1, CXCR-4) and two orphan 7tm receptors (V28 and EBI.1) for their ability
      to allow infection of CD4-negative feline kidney CCC cells by the HIV-2 strains
      ROD/A and ROD/B. We found that ROD/B was able to use CXCR-4 transiently expressed
      in CCC cells, and infection by ROD/A was enhanced 15-fold in the presence of
      sCD4. Feline CCC cells also became permissive to ROD/B and ROD/A entry when
      transiently transfected with the chemokine receptor CCR-3 or the orphan 7tm
      receptor V2B, when cultured in the presence of sCD4. Entry of ROD/A into CCC
      cells expressing CCR-3 could be blocked by 800 ng/ml eotaxin, the natural ligand
      for CCR-3.

PMID- 9143313
TI  - A specific interaction between coat protein and helper component correlates with
      aphid transmission of a potyvirus.
AB  - Specific binding between the coat protein (CP) and the helper component (HC) of
      the tobacco vein mottling potyvirus (TVMV) was characterized using a protein
      blotting-overlay protocol. In this in vitro assay, HC interacted with either
      virions or CP monomers originating from the aphid-transmissible TVMV-AT but not
      from the non-aphid-transmissible TVMV-NAT. There was a strong correlation between
      the aphid transmissibility of a series of TVMV variants having mutations in the
      DAG motif of the CP and their ability to bind HC. Expression of TVMV CP
      derivatives in bacteria allowed a precise determination of the minimum domain
      mediating HC binding. This domain is composed of seven amino acids, including the
      DAG motif (DTVDAGK), located in the N-terminus of the TVMV CP at amino acid
      positions 2 to 8.

PMID- 9143314
TI  - Immunosenescence in HIV pathogenesis.
AB  - Telomeres are complex protein-DNA structures located at the ends of eukaryotic
      chromosomes. In a normal cell, telomere DNA shortens with cell divisions. Such a
      telomere loss may act as a mitotic clock to eventually signal cell cycling exit
      and cellular senescence. In a transversal study, we found a marked decrease in
      telomere length of peripheral blood mononuclear cells in HIV-infected patients
      with advanced immunodeficiency. This telomere reduction concerns T4, T8, and B
      lymphocytes, providing evidence of high turnover of these cells in the course of
      HIV infection. These data suggest that replicative senescence could be involved
      in the final immunosuppression and may have important therapeutical implications.

PMID- 9143315
TI  - E7 oncoprotein of human papillomavirus type 16 expressed constitutively in the
      epidermis has no effect on E7-specific B- or Th-repertoires or on the immune
      response induced or sustained after immunization with E7 protein.
AB  - A line of FVB (H-2q) mice transgenic for the E6/E7 open reading frames of Human
      Papillomavirus type 16 driven from the alpha-A crystallin promoter expresses E7
      mRNA in lens and skin epithelium. E7 protein is detectable in adult skin,
      coinciding with the development of inflammatory skin disease, which progresses to
      papillomata and squamous carcinomata in some mice. By examining the outcome of
      parenteral immunization with E7 protein, we sought to determine whether
      endogenous expression of E7 in skin had induced a preexisting immune outcome,
      i.e., specific immunity or tolerance, or whether the mice remain naive
      ("ignorant") to E7. Our data show that the antibody response to defined E7 B
      epitopes, the proliferative response to Th epitopes, and the delayed-type
      hypersensitivity (DTH) response to whole E7 did not differ between groups of
      young and old E6/E7 transgenic mice (likely having different degrees of lifetime
      exposure to E7 protein) or between E6/E7-transgenic and nontransgenic parental
      strain control mice. Although an E7-specific CTL response could not be induced in
      the H-2q background of these mice, incorporation of a Db allele into the genome
      allowed comparison of Db-restricted CTL responses in E6/E7 transgenic and
      nontransgenic mice. Experiments indicated that the E7-immunization-induced CTL
      response did not differ significantly between E6/E7 transgenic and nontransgenic
      mice. We interpret these results to indicate that in spite of expression of E7
      protein in adult skin, E6/E7 transgenic mice remain immunologically naive
      (ignorant) of E7 epitopes presented by immunization.

PMID- 9143316
TI  - Effect of screening for cancer in the Nordic countries on deaths, cost and
      quality of life up to the year 2017.
AB  - The aim of this study was to evaluate the effects of screening for cancer in the
      Nordic countries. There is sufficient scientific evidence to conclude that
      screening for cervical cancer, breast cancer and colorectal cancer will result in
      a reduction in mortality. The effects on mortality were predicted for the future
      up to the year 2017 assuming that the Nordic countries are covered by screening
      as a nation-wide population-based public health policy and comparing the
      predicted mortality trends with those assuming no screening programmes. For
      cervical cancer the programme as practised in Finland was used as a point of
      reference. For breast cancer and for colorectal cancer the results of randomized
      preventive trials were assumed in the absence of detailed results based on any
      public health policy, i.e., a reduction of 30% in mortality from breast cancer
      and 20% in mortality from colorectal cancer. The assumed ages and frequencies of
      screening ranged from 25 to 59 years at 5-year intervals for cervical cancer,
      from 50 to 69 at 2-year intervals for breast cancer and annual screening from 50
      to 74 years for colorectal cancer. Data on incidence and incidence predicted up
      to the year 2012, mortality, survival and size of the general population were
      employed in the estimation. Age-cohort and age-period-cohort log-linear models
      were applied in predicting future mortality rates with and without screening. The
      choice of the models depended on the age distribution of deaths from each
      particular site of cancer, on changes in public health policy, such as
      establishment of mass-screening, and on the goodness of fit of the model. The
      screening policy assumed would result in 1600 annual deaths prevented out of the
      potential 13,600 deaths in the Nordic countries in 1995, corresponding to 11% of
      the deaths from the three primary sites. Only after the year 2010 will the
      ultimate effect of such a screening policy have as full an effect and in 2013
      2017 the annual number of cancer deaths prevented will be 3900 out of 15,000
      potential deaths, i.e., a 26% reduction. This is equal to 5.7% of all cancer
      deaths in the Nordic countries in 2013-2017 (2.0% for males and 9.7% for
      females). The predicted numbers of annual deaths prevented in 2013-2017 are 1500
      for cervical cancer, 1000 for breast cancer and 1500 for colorectal cancer. Most
      (91%) of the cervical cancers can be prevented, whereas the proportion of breast
      cancer deaths (18%) and colorectal cancer deaths (18%) prevented will be much
      smaller. Costs of the screening programmes were estimated taking into
      consideration the direct costs of screening and savings from advanced disease
      treatment and terminal care. The total cost of screening for cervical, breast and
      colorectal cancer in the Nordic countries in the year 2010 is estimated to be
      $111 m. Cervical cancer screening is estimated to save $17 m yearly in the period
      2008-2012. Screening for cervical cancer is approaching a phase when both the
      effect and costs are relatively stable and it was estimated to be cost-saving.
      The effect of screening for breast and colorectal cancers is expected to become
      apparent gradually during the predicted period due to the increasing number (and
      percentage) of patients diagnosed by screening. When the screening programmes are
      assumed to achieve the optimal effect, the reduction in mortality will increase
      and treatment costs fall, resulting in a substantial decrease in the cost
      effectiveness ratio. In the last considered period (2008-2012) the costs per life
      year gained (breast cancer $15,400, colorectal cancer $5700) are approximately
      one half of those at the onset of screening. The differences in the costs per LYG
      were relatively small between the Nordic countries and mainly dependent on the
      differences in baseline risk of cancer. The total cost of the three screening
      programmes was estimated at $4400 per life years gained in the year
      2010.(ABSTRACT TRUNCATED)

PMID- 9143317
TI  - Cell type and spatial location dependence of cytoplasmic viscosity measured by
      time-resolved fluorescence microscopy.
AB  - Information on the cell type and spatial location dependence of cytoplasmic
      viscosity would be very useful in understanding some of the processes occurring
      in the cell. For this purpose, fluorescent dye kiton red (sulforhodamine B) was
      loaded into a variety of cells such as Swiss 3T3 fibroblasts, human mononuclear
      cells, Sarcoma-180 tumor cells, Chinese hamster ovary cells, plant cells from
      Digitalis lanata, stamen hair cells of Tradescantia, and guard mother cells of
      Allium cepa. Space-resolved measurements of cytoplasmic viscosity were carried
      out by using an experimental set-up wherein a picosecond laser system was coupled
      with an epifluorescence microscope. The spatial resolution of this set-up was
      approximately 1.0 micron, and reliable dynamic fluorescence measurements could be
      obtained from 10(2) to 10(3) fluorescent molecules. Fluorescence lifetime
      measurements showed that a large fraction (approximately 70%) of kiton red was in
      the free form. Fluorescence anisotropy decay of kiton red in cells was analyzed
      by a two population (free and bound) model. The microviscosity of cytoplasm was
      estimated from the anisotropy decay kinetics of the free probe. It was found that
      the cytoplasmic viscosity is dependent on both the cell type and spatial location
      within a cell. Furthermore, both the average value of viscosity and spatial
      variation within a cell were larger in the plant cells when compared to the
      animal cells. Model studies in various simpler systems have shown that the higher
      viscosity observed in some part of the cell could be due to either physical
      restriction and/or the presence of high concentrations of small solutes and
      macromolecules.

PMID- 9143318
TI  - Catalytic properties of lipoamide dehydrogenase from Mycobacterium smegmatis.
AB  - Lipoamide dehydrogenase from Mycobacterium smegmatis was purified to homogeneity
      over 60-fold. Of 20 amino acid residues identified at the amino terminus of the
      enzyme, 18 and 17 were identical to the sequences of Mycobacterium leprae and
      Pseudomonas fluorescens lipoamide dehydrogenases, respectively. The visible
      spectrum of the isolated enzyme was characteristic of a flavin in apolar
      environment. Reduction of the enzyme with dithionite results in the appearance of
      an absorbance shoulder at 530-550 nm, suggesting that reducing equivalents of the
      two-electron reduced enzyme reside predominantly on the redox-active
      disulfidedithiol. The kinetic mechanism of the forward (NAD+ reducing) and
      reverse (NADH oxidizing) reactions proved difficult to study due to severe
      substrate inhibition by NAD+ and NADH. The rate of lipoamide reduction was found
      to depend upon the NAD+/NADH ratio, with the reaction being activated at low
      ratios and inhibited at high ratios. The use of 3-acetylpyridine adenine
      dinucleotide allowed initial velocity kinetics to be performed and revealed that
      the kinetic mechanism is ping pong. In addition to catalyzing the reversible
      oxidation of dihydrolipoamide, the enzyme displayed high oxidase activity (30% of
      the lipoamide reduction rate), hydrogen and t-butyl peroxide reductase activity
      (10% of the lipoamide reduction rate), and both naphthoquinone and benzoquinone
      reduction (approximately 200% of the lipoamide reduction rate). The enzyme failed
      to catalyze the redox cycling of nitrocompounds, but could anaerobically reduce
      nitrofurazone. The lipoamide-reducing reaction was reversibly inactivated by
      sodium arsenite, but no decrease in diaphorase activity was observed under these
      conditions.

PMID- 9143319
TI  - Protein phosphatase-1 alpha, gamma 1, and delta: changes in phosphorylation and
      activity in mitotic HeLa cells and in cells released from the mitotic block.
AB  - Protein phosphatase-1 is phosphorylated "in vitro" by cdc2-cyclin B (E. Villa
      Moruzzi, FEBS Lett. 304, 211-215, 1992). In the present study the phosphatase-1
      isoforms alpha, gamma 1, and delta were analyzed in mitotic (nocodazole-blocked)
      HeLa cells. Phosphorylation on threonine increased in gamma 1 and delta at
      mitosis. alpha was phosphorylated only in mitotic cells and mainly on serine.
      Exposure of permeabilized mitotic cells to a peptide that inhibits cdc2 decreased
      the phosphorylation of the isoforms. Cell fractionation indicated that
      phosphatase-1 was over 90% inactivated and phosphorylated in the soluble, but not
      in the chromosomal fraction of mitotic cells. Immunoprecipitation from the
      mitotic soluble fraction indicated that only gamma 1 and delta, but not alpha,
      were inactivated. Altogether the data pointed to a correlation between
      phosphatase-1 inactivation and phosphorylation in mitotic cells. cdc2-cyclin B
      might be the kinase (or one of the kinases) that phosphorylates phosphatase-1. In
      cells released from the mitotic block, the phosphatase-1 activity in the soluble,
      but not in the nuclear fraction, increased progressively, reaching control values
      by 16 h. Immunoprecipitation indicated that the increase in activity was due to
      alpha and delta only. On the other hand, the activity of gamma 1 remained low,
      and this was also the only isoform that remained phosphorylated, though less than
      in mitotic cells. Also in the case of the cells released from mitosis, a
      correlation may exist between phosphorylation and inactivation of phosphatase-1.
      However, the regulation of phosphatase-1 is complex and may involve also
      regulatory subunits that are still unknown. Altogether, the results indicated the
      differential regulation of the phosphatase-1 isoforms both at mitosis and in G1
      cells.

PMID- 9143320
TI  - Isolation, cDNA cloning, biological properties, and carbohydrate binding
      specificity of sieboldin-b, a type II ribosome-inactivating protein from the bark
      of Japanese elderberry (Sambucus sieboldiana).
AB  - A type II ribosome-inactivating protein (RIP) was isolated from the bark tissue
      of Japanese elderberry (Sambucus sieboldiana) and named sieboldin-b. Sieboldin-b
      is a heterodimeric protein consisting of 27- and 33-kDa subunits and showed
      strong ribosome-inactivating activity in vitro but did not show in vivo toxicity.
      The amino acid sequence of sieboldin-b deduced from the structure of the cDNA
      showed that both subunits of sieboldin-b are encoded on a single precursor
      polypeptide. Sieboldin-b has a structure homologous with the Neu5Ac(alpha 2
      6)Gal/GalNAc-specific bark lectin from S. sieboldiana (SSA) and also typical type
      II RIPs such as ricin and abrin. Detailed analyses of carbohydrate binding
      properties of sieboldin-b revealed that sieboldin-b binds to Gal/GalNAc, similar
      to ricin/abrin, in spite of its highly homologous structure with SSA. The
      biological properties of these toxins/lectins are compared, and the possible
      explanation for such diversity is discussed.

PMID- 9143321
TI  - Saccharomyces cerevisiae expresses two genes encoding isozymes of 5
      aminoimidazole-4-carboxamide ribonucleotide transformylase.
AB  - We have isolated and cloned two Saccharomyces cerevisiae genes which encode
      isozymes of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase,
      the ninth step of the de novo purine biosynthesis pathway. This reaction involves
      the formylation of AICAR using 10-formyltetrahydrofolate as the formyl donor.
      ADE16 is located on chromosome XII and encodes an open reading frame of 591 amino
      acids. ADE17 is located on chromosome XIII and encodes an open reading frame of
      592 amino acids. The deduced amino acid sequences of the two genes are 84%
      identical to each other and are 60-63% identical to the chicken and human
      bifunctional AICAR transformylase/IMP cyclohydrolase amino acid sequences.
      Disruption of the two chromosomal yeast genes resulted in adenine auxotrophy,
      while the expression of either gene alone was sufficient to support growth
      without adenine. In vitro assays of AICAR transformylase activity demonstrated
      the lack of IMP production in the double disruptant strain. S. cerevisiae is the
      only organism known thus far to possess isozymes of this protein. Because it is
      likely that the proteins encoded by ADE16 and ADE17 also contain IMP
      cyclohydrolase activity, these two genes complete the set of clones and mutants
      for the entire de novo purine biosynthesis pathway in yeast.

PMID- 9143322
TI  - Molecular cloning and characterization of a novel putative STE20-like kinase in
      guinea pigs.
AB  - Protein kinases play a key role in cell growth and differentiation. We have
      isolated the cDNA of a novel protein serine/threonine kinase (referred to as
      STE20-like kinase (SLK) from a guinea pig liver cDNA library with a probe
      generated by a cloning approach based on the polymerase chain reaction. The
      encoded polypeptide (1231 amino acids, M(r) 141,079) contains all conserved
      subdomains characteristic of the protein serine threonine kinase family. A
      hemagglutinin-tagged SLK expressed artificially in COS7 cells was
      hyperphosphorylated by anisomycin. By Northern blot analysis, SLK mRNA was
      detected in all organs examined: brain, lung heart, liver, kidney, spleen,
      testis, and eosinophils. Sequence comparisons of its catalytic domain related SLK
      to p21-activated kinase family of protein serine/threonine kinases. Its
      noncatalytic domain comprises several intriguing structural features, including
      the acidic region and the nuclear targeting sequence. This noncatalytic domain
      exhibited no extended similarity with other proteins. Thus, SLK is a protein
      serine/threonine kinase which contains an unknown regulatory domain(s).

PMID- 9143323
TI  - cDNA cloning, heterologous expression, and characterization of mouse CYP2G1, an
      olfactory-specific steroid hydroxylase.
AB  - CYP2G1 is expressed specifically in the olfactory mucosa in rabbits and rats. In
      the present study, a full-length cDNA for mouse CYP2G1 was obtained using a PCR
      approach with RNA preparations from the olfactory mucosa of C57BL/6 mice.
      Sequence comparisons indicated that mouse CYP2G1 is highly homologous in deduced
      amino acid sequence to rabbit (82.4% identity) and rat CYP2G1 (94.9% identity).
      RNA blot and immunoblot analyses indicated that mouse CYP2G1 is expressed only in
      the olfactory mucosa. The coding region of the mouse CYP2G1 cDNA was cloned into
      a baculoviral expression vector for heterologous production of the enzyme in
      cultured insect cells. Heterologously expressed mouse CYP2G1 was active in a
      reconstituted system toward testosterone and progesterone, producing all the
      major metabolites detected in olfactory microsomal reactions, including 15 alpha
      , 15 beta-, and 2 beta-hydroxytestosterone from testosterone and two unidentified
      metabolites from progesterone. Kinetic analysis indicated that mouse CYP2G1 has
      relatively high affinities toward the steroid substrates, with K(m) values in the
      micromolar range for both testosterone and progesterone. At a substrate
      concentration of 10 microM, microsomes of olfactory mucosa had much higher
      turnover numbers toward testosterone and progesterone than hepatic microsomes,
      consistent with the olfactory-specific expression of a high-affinity sex steroid
      hydroxylase. These findings will facilitate further molecular genetics studies on
      the biological function of CYP2G1 in a mouse model.

PMID- 9143324
TI  - Mouse cytochrome P450 (Cyp3a11): predominant expression in liver and capacity to
      activate aflatoxin B1.
AB  - S1 mapping analysis for the expression of Cyp3a11 and Cyp3a13 indicated that
      Cyp3a11 mRNA is predominantly expressed in mouse liver, compared with that of
      Cyp3a13. In addition, all of six inducers, such as dexamethasone, 3
      methylcholanthrene, phenobarbital, polychlorinated biphenyl, pregnenolone 16
      alpha-carbonitrile, and rifampicin, increased the expression of the Cyp3a11 mRNA
      more extensively than that of Cyp3a13. The level of mRNAs corresponding to
      Cyp3a11 and Cyp3a13 reached the maximum level between 4 and 8 weeks after birth.
      Cyp3a11 enzyme was expressed into CR119 cells which had been established as a
      cell line stably expressing NADPH-cytochrome P450 reductase cDNA of guinea pigs.
      These transformants showed aflatoxin B1-dependent cytotoxicity in proportion to
      the amounts of Cyp3a11 mRNA. This cytotoxicity was enhanced by 7,8-benzoflavone,
      a known activator of CYP3A protein. Based on these results, we confirm that CYP3A
      in the mouse, which is an animal species known to be relatively insensitive to
      aflatoxin B1 genotoxicity, can activate this mycotoxin efficiently.

PMID- 9143325
TI  - Accumulation of sulfoquinovosyl-1-O-dihydroxyacetone in a sulfolipid-deficient
      mutant of Rhodobacter sphaeroides inactivated in sqdC.
AB  - The biosynthesis of the sulfolipid sulfoquinovosyl diacylglycerol in the purple
      bacterium Rhodobacter sphaeroides requires at least four genes:sqdA, sqdB, sqdC,
      and sqdD. As part of our strategy aimed at the elucidation of the function of the
      different sqd gene products, we insertionally inactivated sqdC of R. sphaeroides.
      The resulting sqdC null mutant showed only a 90% reduction in sulfolipid content.
      Apparently, the sqdC gene product is required for optimal sulfolipid
      biosynthesis, but either catalyzes no essential reaction in the pathway or can be
      functionally replaced to a certain extent by a different protein. The mutant
      accumulated a 35S-labeled compound that was purified to homogeneity from cell
      extracts. Matrix-assisted laser desorption mass spectrometry and nuclear magnetic
      resonance spectroscopy provided conclusive structural evidence to identify the
      compound as alpha-D-sulfoquinovosyl-1-O-dihydroxyacetone that exists in two
      interconvertible, keto and hemiacetal forms. Incubation of wild-type protein
      extracts with the labeled compound did not result in the incorporation into
      sulfolipid as would be expected for an intermediate of the pathway. Based on our
      results we propose that the sqdC gene product mediates the substrate specificity
      of the UDP-sulfoquinovose:diacylglycerol sulfoquinovosyltransferase that is
      encoded by sqdD and that catalyzes the final reaction of sulfolipid biosynthesis.

PMID- 9143326
TI  - Reconstitution of the fatty acid hydroxylase activity of cytochrome P450BM-3
      utilizing its functional domains.
AB  - Cytochrome P450BM-3, a catalytically self-sufficient fatty acid monooxygenase
      from Bacillus megaterium, is a multidomain protein containing heme, FAD, and FMN.
      Previous attempts to reconstitute the fatty acid monooxygenase activity of intact
      P450BM-3 utilizing equimolar concentrations of the separate heme (BMP) and
      reductase (BMR) domains, have been unsuccessful because two-electron reduced FMN,
      which rapidly accumulates, is incapable of electron transfer to the heme iron.
      The present study of the reconstitution of the monooxygenase activity of P450BM-3
      utilized combinations of the different functional domains of P450BM-3. For this
      purpose, the FAD/NADPH- and FMN-binding domains of P450BM-3 as well as the
      combination of the heme- and FMN-binding domains (BMP/FMN) have been expressed
      and purified. The reconstitution systems, consisting of either BMP/FMN and FAD
      domains or BMP, FMN, and FAD domains, were still less effective than the
      holoenzyme, P450BM-3, but were much more effective than a system consisting of
      BMP and BMR. The maximal rate of oxidation of palmitic acid by the newly
      developed reconstitution systems is still only approximately 5% of the activity
      of the holoenzyme. The reconstitution systems produced omega-1, omega-2, and
      omega-3 monohydroxy palmitic acid, but not the secondary products of palmitic
      acid hydroxylation observed with the holoenzyme. The physical cause of the
      inability to reconstitute fully the maximal activity of the holoenzyme as well as
      the lack of secondary product formation is not presently understood.

PMID- 9143327
TI  - Oxalate oxidase from barley roots: purification to homogeneity and study of some
      molecular, catalytic, and binding properties.
AB  - Oxalate oxidase (OXO) was purified to homogeneity in three steps from roots of
      barley seedlings. The purification method comprised: (i) thermal treatment (60
      degrees C, 10 min), (ii) affinity chromatography on immobilized either Procion
      turquoise MX-G dye or biomimetic aminoethyl oxamic blue dye, and (iii) affinity
      chromatography on immobilized lectin concanavalin A (overall performance: 1096
      fold purification, 42% recovery). The purified enzyme has a specific activity of
      34 U mg-1 (25 degrees C), and is a homopentamer of M(r) approximately 125,000
      (HPLC analysis) showing a single band on SDS-polyacryl-amide gel electrophoresis
      (M(r) approximately 26,000) after staining with silver nitrate. The kinetic
      constants of the purified enzyme for oxalate are K(m) 0.27 mM and kcat 22 s-1 (37
      degrees C), whereas at [oxalate] > or = 4 mM the enzyme exhibited substrate
      inhibition. Barley root OXO contains no prosthetic group absorbing at 370 or 450
      nm, and riboflavin and FAD have no effect on its activity. The enzyme is
      activated by 1 mM each of Ca2+ (1.7-fold) and Pb2+ (2.6-fold). Irreversible
      inactivation studies with denatured (70 degrees C) and native (37 degrees C)
      enzyme using the sulfhydryl-attacking reagent 5,5-dithiobis(2-nitrobenzoic) acid
      (1.4 mM), in the presence and absence of SDS, respectively, have shown that
      denatured OXO (4% SDS, 10 min, 100 degrees C) exhibited 10 HS groups per
      molecule, whereas native OXO displayed one accessible HS group per molecule after
      approximately 15 min incubation and, over the same period, maintained its
      catalytic activity to 90%. Furthermore, native OXO treated with beta
      mercaptoethanol (1 mM) lost 83% of its catalytic activity within 5 min. These
      findings indicate that some cysteines may preserve the catalytic activity of OXO
      by maintaining the integrity of its tertiary structure via disulfide bond
      formation.

PMID- 9143328
TI  - Unusual usage of noncomplementary dinucleotide primers by the yeast mitochondrial
      RNA polymerase.
AB  - The mitochondrial RNase P RNA gene in yeast Saccharomyces cerevisiae is
      transcribed from a variant mitochondrial promoter (SP). The sequence of this SP
      promoter [TATAAGAAG (+2)] differs from the conserved mitochondrial promoter
      sequence [TATAAGTAA (+2)] by-1T-->A and +2A-->G nucleotide substitutions. To
      determine the effect of these nucleotide alterations in mitochondrial promoter
      function, an in vitro transcription analysis was carried out. In the presence of
      high concentrations of rNTPs (i.e., 125 microM), transcription initiation on the
      wild-type or variant promoter occurred at the conventional 3' adenine nucleotide.
      However, at low rNTP concentrations (i.e., 5 microM) and in the presence of a
      complementary dinucleotide primer corresponding to positions -1 + 1, the
      mitochondrial RNA polymerase started transcription one nucleotide upstream of the
      conventional start site. Surprisingly, in the presence of some noncomplementary
      dinucleotides (i.e., GpA or CpA), which do not have perfect Watson-Crick base
      pairing with the initiator sequence, transcriptional initiation also occurred
      with the SP promoter but not with the conserved promoter sequence. This finding
      is the first example of utilization of noncomplementary dinucleotide primer by an
      RNA polymerase. Further analysis of mitochondrial promoter function by site
      directed mutagenesis determined that the guanine nucleotide at position +2 is
      mainly responsible for this unusual function of the SP promoter.

PMID- 9143329
TI  - Competition between polyanions in glomerular binding and renal clearance.
AB  - This study tests the hypothesis that exogenous polyanions may accumulate in the
      glomerular capillary wall and thereby provide fixed negative charges that will be
      effective, through electrostatic interactions, in governing the transcapillary
      transport of charged molecules. We have tested the effects of high concentrations
      of dextran sulfate, heparin, and orosomucoid on the fractional clearance of
      albumin and dextran sulfate using the isolated perfused kidney technique. We
      demonstrate that all these exogenous polyanions are without effect on the
      fractional clearance of albumin. Augmentation of glomerular charge through the
      binding of dextran sulfate or orosomucoid is very small compared to the charge
      augmentation by albumin. These results agree with previous studies which
      demonstrate that electrostatic interactions governing glomerular transcapillary
      wall transport are negligible. This study also demonstrates that there is no
      plausible correlation between the fixed negative charge contributed by endogenous
      metabolically labeled glomerular heparan sulfate and the manifestation of
      apparent charge selectivity as determined with dextran sulfate. The results are
      also consistent with previous studies that the renal processing of both dextran
      sulfate and albumin is associated with specific cellular uptake.

PMID- 9143330
TI  - Differential inhibition of fungal amd mammalian squalene epoxidases by the
      benzylamine SDZ SBA 586 in comparison with the allylamine terbinafine.
AB  - The allylamine class of antifungal compounds are specific inhibitors of squalene
      epoxidase (SE). However, depending on their chemical structure, allylamine
      derivatives can be highly selective for either fungal or mammalian SEs. All
      allylamines tested previously, irrespective of their selectivity, inhibit fungal
      SEs in a noncompetitive manner and mammalian SEs in a competitive manner. Here we
      have analyzed the inhibitory properties of the benzylamine SDZ SBA 586 toward
      fungal and mammalian SEs in comparison to the systemic antimycotic terbinafine,
      SDZ SBA 586 was, like terbinafine a selective inhibitor of fungal SE. Microsomal
      SE from the pathogenic yeast candida albicans was sixfold more sensitive to SDZ
      SBA 586 than to terbinafine, C50: 8 nM versus 44 nM, while the enzyme from the
      dermatophyte fungus Trichophyton rubrum was slightly less sensitive to SDZ SBA
      586 than to terbinafine, IC50: 39 and 18 nM, respectively. Similarly to
      terbinafine, SDZ SBA 586 inhibited the yeast enzyme in non competitive manner,
      SDZ SBA 586 also inhibited mammalian microsomal SEs, but only at micromolar
      concentrations. It was more active than terbinafine toward both guinea pig SE,
      IC50: 2 microM versus 4 microM, and rat SE, IC50: 11 microM versus 87 microM.
      However, in contrast to terbinafine as well as allylamines selective for
      mammalian SE, SDZ SBA 586 was a noncompetitive inhibitor of rat microsomal SE.
      Interestingly, depending on the source of microsomal SE, binding of terbinafine
      and SDZ SBA 586 exhibited a positive, indifferent, or negative cooperativity,
      suggesting that SE is an oligomeric enzyme.

PMID- 9143331
TI  - CDNA cloning, heterologous expression, and characterization of rat intestinal
      CYP2J4.
AB  - The small intestine is the major portal of entry of ingested xenobiotics.
      Previous studies from this and other laboratories indicated that at least 6 of
      the 33 xenobiotic metabolizing forms of P450 currently identified are expressed
      in rat small intestinal epithelial cells. In the present study, a previously
      unidentified rat P450, designated CYP2J4, was identified in rat small intestine
      using PCR. The full-length CYP2J4 cDNA contains an open reading frame for a
      protein of 501 residues and is 72.5 and 75.8% identical to rabbit CYP2J1 and
      human CYP2J2, respectively, in deduced amino acid sequences. The coding region of
      CYP2J4 cDNA has been cloned into a baculoviral expression vector (pVL1392) and
      expressed in cultured Spodoptera frugiperta (SF9) cells. The heterologously
      expressed CYP2J4 protein displayed a typical p450 CO-difference spectrum, with
      maximum absorbance at 449 nm. When purified to near electrophoretic homogeneity,
      it was active toward arachidonic acid in a reconstituted system with NADPH-P450
      reductase and phospholipid, producing both hydroxyeicosatetraenoic and
      epoxyeicosatrienoic acids. RNA blot analysis with CYP2J4 cDNA as a probe detected
      two mRNA species, about 2.0 and 2.4 kb, respectively, in RNA preparations from
      liver, intestine, olfactory mucosa, kidney, heart, and lung. The 2.0-kb mRNA
      species was abundant in liver, small intestine, and olfactory mucosa, whereas the
      2.4-kb mRNA species was predominant only in the olfactory mucosa. Immunoblot
      analysis of microsomal fractions from different rat tissues with a polyclonal
      anti-peptide antibody to CYP2J4 detected a protein with the same electrophoretic
      mobility as purified CYP2J4 most abundantly in small intestine and to a lesser
      extent in liver and other immunoreactive proteins with slightly higher
      electrophoretic mobility than purified CYP2J4 in a number of tissues, including
      small intestine, liver, kidney, lung, and olfactory mucosa. The predominant
      distribution of CYP2J4, which has activity toward arachidonic acid, is
      provocative, but its physiological function is as yet unknown.

PMID- 9143332
TI  - Glutathione S-transferases of female A/J mouse lung and their induction by
      anticarcinogenic organosulfides from garlic.
AB  - Glutathione S-transferases (GSTs) of female A/J mouse lung have been purified and
      characterized for their (a) structural interrelationships, (b) substrate
      specificities toward the ultimate carcinogenic metabolite of benzo(a)pyrene (BP),
      (+)-anti-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-oxy-7,8,9,10
      tetrahydrobenzo(a)pyrene [(+)-anti-BPDE], and (c) induction by three naturally
      occurring organosulfides (OSCs)-from garlic [diallyl sulfide (DAS), diallyl
      trisulfide (DATS) and dipropyl sulfide (DPS)], which significantly differ in
      their efficacy against BP-induced lung cancer in mice. The GST activity in the
      lung was due to two alpha class (pI 9.4 and 6.0), two mu class (pI 8.7 and 8.6),
      and one pi class (pI 8.9) isoenzyme. The GST isoenzyme profile of the lung was
      different from that of the A/J mouse forestomach, which also is a target organ
      for BP-induced cancer in mice. Noticeably, an alpha class heterodimeric isoenzyme
      (pI 9.5) present in the forestomach of A/J mouse, which is exceptionally
      efficient in the glutathione (GSH) conjugation of (+)-anti-BPDE [X. Hu, S.K.
      Srivastava, H. Xia, Y. C. Awasthi, and S. V. Singh (1996) J. Biol. Chem. 271,
      32684-32688], could not be detected in the lung. The specific activities of the
      lung GSTs in the GSH conjugation of (+)-anti-BPDE were in the order of GST 8.9 >
      GST 8.7 > GST 9.4 > GST 6.0. While DPS treatment did not increase the levels of
      any pulmonary GST isoenzyme, the expression of pi class GST 8.9 was significantly
      increased in response to both DAS and DATS administrations. Interestingly, DATS,
      an OSC which lacks activity against BP-induced lung cancer in mice, was a
      relatively more potent inducer of pi class GST isoenzyme than DAS, which is a
      potent inhibitor of BP-induced lung tumorigenesis. The results of the present
      study suggest that a mechanism(s) other than GST induction is likely to be
      responsible for the differential effects of DAS and DATS on BP-induced lung
      cancer in mice. Our results also suggest that relatively lower efficacies of the
      OSCs against BP-induced lung cancer than against forestomach neoplasia may be
      attributed to (a) a lack of expression in the lung of an isoenzyme corresponding
      to forestomach GST 9.5 and (b) a comparatively lower level of induction of pi
      type GST in the lung than in the forestomach by these OSCs.

PMID- 9143333
TI  - The effect of fasting/refeeding and insulin treatment on the expression of the
      regulatory genes of ketogenesis in intestine and liver of suckling rats.
AB  - The influence of fasting/refeeding and insulin treatment on ketogenesis in 12-day
      old suckling rats was studied in intestine and liver by determining mRNA levels
      and enzyme activity of the two genes responsible for regulation of ketogenesis:
      carnitine palmitoyl transferase I (CPT I) and mitochondrial HMG-CoA synthase.
      Fasting produced hardly any change in mRNA or activity of CPT 1 in intestine, but
      led to a decrease in mitochondrial (mit.) HMG-CoA synthase. In liver, while mRNA
      levels and activity for CPT I increased, neither parameter was changed in HMG-CoA
      synthase. The comparison of these values with the ketogenic rate of both tissues
      under the fasting/refeeding treatment shows that HMG-CoA synthase could be the
      main gene responsible for regulation of ketogenesis in suckling rats. The small
      changes produced in serum ketone bodies in fasting/refeeding, with a profile
      similar to the ketogenic rate of the liver, indicate that liver contributes most
      to ketone body synthesis in suckling rats under these experimental conditions.
      Short-term insulin treatment produced increases in mRNA levels and activity in
      CPT I in intestine, but it also decreased both parameters in mit. HMG-CoA
      synthase. In liver, graphs of mRNA and activity were nearly identical in both
      genes. There was a marked decrease in mRNA levels and activity, resembling those
      values observed in adult rats. As in fasting/refeeding, the ketogenic rate
      correlated better to mit. HMG-CoA synthase than CPT I, and liver was the main
      organ regulating ketogenesis after insulin treatment. Serum ketone body
      concentrations were decreased by insulin but recovered after the second hour.
      Long-term insulin treatment had little effect on the mRNA levels for CPT I or
      mit. HMG-CoA synthase, but both the expressed and total activities of mit. HMG
      CoA synthase were reduced by half in both intestine and liver. The ketogenic rate
      of both organs was decreased to 40% by long-term insulin treatment. The different
      effects of refeeding and insulin treatment on the expression of both genes, on
      the ketogenic rate, and on ketone body concentrations are discussed.

PMID- 9143334
TI  - Purification and subunit structure of extracellular superoxide dismutase from
      mouse lung tissue.
AB  - The first purification of mouse extracellular superoxide dismutase (EC-SOD) and
      the analysis of the native enzyme are described. Mouse EC-SOD was purified from
      lung tissues with a high recovery (41%) and a specific polyclonal antibody
      against the purified enzyme was obtained. The purified enzyme had a strong
      affinity for, heparin and a molecular mass of 150 kDa (estimated by a gel
      filtration chromatography). The native mouse EC-SOD was composed of two different
      sizes of subunits, a M(r) of 33 and 35 kDa (determined by SDS-PAGE). The 35-kDa
      subunit had an interchain disulfide bond at the C-terminus and existed as a
      covalent dimer in the molecule, whereas the 33-kDa subunit resulted from the 35
      kDa subunit by truncating its C-terminus as a posttranslational modification,
      with resultant loss of the interchain disulfide bond. These results suggest that
      the native mouse EC-SOD is a heterotetramer composed of two different dimers,
      with or without a covalent bond.

PMID- 9143335
TI  - The copper- and zinc-containing superoxide dismutase from Escherichia coli:
      molecular weight and stability.
AB  - The periplasmic Cu,Zn superoxide dismutase (Cu,ZnSOD) from Escherichia coli has
      been shown by sedimentation equilibrium to be a monomer with a molecular weight
      of approximately 17,000. The enzyme suffered a reversible inactivation when
      heated to 70 degrees C. This was minimized by added Cu(II) or Zn(II). Heat
      lability was greater in phosphate than in Tris buffer. The enzyme exhibited a
      time-dependent inactivation by Hg(II) and this too was greater in phosphate than
      in Tris. This behavior can be explained by a modest affinity of the enzyme for
      Cu(II) and Zn(II) which results in a dissociation/association equilibrium.
      Elevation of the temperature shifts this equilibrium toward dissociation and
      phosphate sequesters the released metals making them less available for
      reinsertion at the active site. Hg(II) competes for occupancy of the active site
      and there were more unoccupied sites in phosphate than in Tris. A parallel was
      drawn between the E. coli Cu,ZnSOD and FALS varients of human Cu,ZnSOD, which are
      also relatively unstable and exhibit low affinity for Cu(II).

PMID- 9143336
TI  - Ceramide glucosylation in bean hypocotyl microsomes: evidence that steryl
      glucoside serves as glucose donor.
AB  - The formation of glucosylceramide, the predominant sphingolipid in plant tissues,
      was examined in microsomes from wax bean hypocotyls. Membranes were incubated
      with UDP-[14C]glucose in an assay mixture. The lipid extracts obtained from the
      assays were separated by thin-layer chromatography, and the radioactivity
      incorporated into glucosylceramide, steryl glucoside, and acylated steryl
      glucoside was determined. Although the formation of glucosylceramide was detected
      and characterized, several lines of evidence contradicted the assumption that UDP
      glucose is the immediate glucose donor for glucosylceramide formation in plants:
      PDMP (DL-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol), an inhibitor of
      ceramide glucosyltransferase in animal tissues, did not inhibit glucosylceramide
      formation in bean microsomes. Addition of UDP-glucose pyrophosphorylase during
      the assay to degrade UDP-[14C]glucose blocked the further production of labeled
      steryl glucoside, but did not prevent the continued formation of labeled
      glucosylceramide. Omitting UDP-[14C]glucose and including steryl [14C]glucoside
      in the assay resulted in the formation of labeled glucosylceramide. Collectively,
      these results suggest that glucosylceramide formation in plants does not utilize
      UDP-glucose as the immediate glucose donor, as has been demonstrated for the
      reaction in animal tissues, and that steryl glucoside serves as glucose donor for
      ceramide formation. This study, the first to examine glucosylceramide formation
      in plants, provides evidence for a novel enzymatic reaction in sphingolipid
      synthesis as well as a new, metabolic role for steryl glucoside in plant tissues.

PMID- 9143337
TI  - Identification of novel metabolites of prostaglandin E2 formed by isolated rat
      hepatocytes.
AB  - The metabolism of prostaglandin E2 (PGE2) in isolated rat hepatocytes led to the
      formation of four major as well as several minor products which were structurally
      characterized using electrospray tandem mass spectrometry. The major metabolites
      identified included dinor-PGE1, dinor-PGE2, and tetranor-PGE1 and the taurine
      conjugates of dinor-PGE1 and dinor-PGE2. Several minor metabolites including the
      taurine conjugates of PGE2 and tetranor PGE1 along with a glucuronide conjugate
      of PGE2 were also identified. These taurine conjugates had not been previously
      identified in studies of PGE2 metabolism, yet comprised nearly 50% of the mixture
      of metabolites after 40-min incubations. Experiments carried out with deuterium
      labeled PGE2 ([3,3,4,4-D4]PGE2) resulted in the complete loss of all deuterium
      atoms in dinor-PGE1, dinor-PGE2, and tetranor metabolites during incubation with
      hepatocytes. Metabolism via classic beta-oxidation pathways would predict one
      deuterium atom retained by dinor-PGE1 and two deuterium atoms retained by dinor
      PGE2. When PGE2 was incubated with isolated rat hepatocytes in buffer containing
      30% D2O, substantial incorporation (30%) of one deuterium atom could be observed
      in the dinor metabolites along with 10% incorporation into the tetranor and
      residual PGE2. Deuterium-labeled PGE1 ([3,3,4,4-D4]PGE1) was metabolized to D2
      dinor-PGE1, tetranor-PGE1, and the taurine conjugate of D2-dinor-PGE1 by isolated
      rat hepatocytes. The loss of deuterium during metabolism of the deuterated
      substrates of PGE2, but not PGE1, as well as the incorporation of deuterium atoms
      from the aqueous solvent into PGE2 metabolites suggested that the delta 5 double
      bond and sequential isomerization reactions lead to eventual exchange of the
      protons from carbon atom 4 of PGE2 with water.

PMID- 9143338
TI  - Diminished susceptibility to proteolysis after protein modification by the lipid
      peroxidation product malondialdehyde: inhibitory role for crosslinked and
      noncrosslinked adducted proteins.
AB  - The lipid peroxidation product malondialdehyde forms adducts with proteins that
      are detected during routine assays for protein carbonylation. To test whether
      this damage alters the susceptibility of a protein to proteolysis, we treated
      bovine serum albumin with various concentrations of malondialdehyde and examined
      its susceptibility to digestion by alpha-chymotrypsin. In keeping with findings
      concerning the consequences of protein damage by other carbonyl products of lipid
      peroxidation, we found that malondialdehyde-modified protein was resistant to
      proteolysis. Since significant protein crosslinking occurred during modification
      with malondialdehyde, we investigated the possibility that crosslinked proteins
      were acting as proteolytic inhibitors. Malondialdehyde-modified proteins were
      resolved into crosslinked and noncrosslinked forms and the effectiveness of both
      species as proteolytic antagonists was examined. While both forms of
      malondialdehyde-adducted proteins were more potent proteolytic inhibitors than
      unmodified albumin, there were no significant differences in inhibitory potency
      between crosslinked and noncrosslinked proteins. Our findings suggest that
      malondialdehyde-modification produces protease-resistant proteins without an
      obligatory role for crosslinking.

PMID- 9143339
TI  - N-acetylglucosamine-6-phosphate deacetylase from Escherichia coli: purification
      and molecular and kinetic characterization.
AB  - N-Acetylglucosamine-6-phosphate deacetylase (E.C. 3.5.1.25), an enzyme of the
      amino sugar utilization pathway, has been purified from an overproducing strain
      of Escherichia coli. The enzyme is a tetramer of identical 41-kDa subunits. The
      sedimentation coefficient of the oligomer is 6.5 s(20),w and it has a pI of 4.9.
      The circular dichroism spectrum of the enzyme in the far uv range suggests that
      it is a protein belonging to the alpha/beta structural family. In the native
      enzyme, two thiols per chain are titrated with 5-5'-dithio-bis(2-nitrobenzoate)
      (NbS2); one reacts rapidly, the other more slowly. The reaction of the more
      reactive sulfhydryl completely inhibits the activity of the enzyme. Three thiols,
      of the total of eight per subunit of the native enzyme, are modified by methyl
      iodide without significantly changing the kinetic parameters; the methylated
      enzyme becomes insensitive to NbS2 inhibition. One of the enzyme reaction
      products, glucosamine 6-phosphate, completely protects this thiol from NbS2
      reaction. The kinetics of the deacetylase reaction have been studied both in the
      forward direction and in the backward direction. The reverse reaction is strongly
      unfavored and is probably physiologically insignificant, but it was useful for
      obtaining a better kinetic description of the enzyme. A sequential mechanism,
      with ordered release of products and a slow isomerization of the enzyme-acetate
      complex, is proposed. This model is supported by data from substrate and product
      inhibition patterns in both directions of the reaction.

PMID- 9143340
TI  - Purification and characterization of protein kinase CK2 from Candida albicans:
      evidence for the presence of two distinct regulatory subunits beta and beta'.
AB  - Protein kinase CK2 of Candida albicans has been purified to near homogeneity by a
      procedure which involves chromatography on DEAE-cellulose, phosphocellulose, Q
      Sepharose, and heparin-agarose. The purified enzyme has the characteristic
      properties of animal and yeast CK2, i.e., it utilizes ATP as well as GTP as
      phosphate donor, phosphorylates serine and threonine residues on casein, is
      inhibited by low concentrations of heparin, and is stimulated by NaCl and
      polycationic compounds such as polylysine, spermine, and spermidine. The native
      form of the enzyme exhibits a molecular mass of 159 kDa, and SDS-PAGE analysis
      indicates that it is composed of four polypeptides with relative molecular masses
      of 44, 39, 37 and 36 kDa. The 39- and 37-kDa polypeptides were identified as
      distinct catalytic subunits alpha and alpha' on the basis of in situ
      phosphorylation assays and immunological recognition with heterologous
      antibodies. The purified kinase undergoes autophosphorylation on the 44- and 36
      kDa polypeptides, a characteristic of the beta subunits from other species.
      Antibodies raised against the beta subunit of Drosophila melanogaster and human
      CK2 crossreact only with the 36-kDa polypeptide. The 44-kDa polypeptide was
      identified as an unusually large beta' subunit by Western blotting with an
      antibody raised against the beta' subunit of Saccharomyces cerevisiae. All these
      data suggest that C. albicans CK2 has an alpha alpha' beta beta' heterotetrameric
      composition similar to that found in S. cerevisiae.

PMID- 9143341
TI  - Engineered porcine pepsinogen exhibits dominant unimolecular activation.
AB  - An engineered pepsinogen, which was a fusion protein of thioredoxin and
      pepsinogen, exhibited dominant self-activation (unimolecular reaction;
      intramolecular activation) in contrast to recombinant pepsinogen which exhibited
      both unimolecular and bimolecular reactions (intermolecular activation mediated
      by pepsin released during activation). At pH values of 1.1, 2.0, and 3.0,
      activation curves for the engineered pepsinogen were hyperbolic rather than
      sigmoidal, indicating that self-activation was the dominant activation mechanism
      in comparison to the slower bimolecular activation. To confirm which activation
      mechanism was dominant, an equal mole of pepsin was added to accelerate the
      bimolecular reaction during activation. The addition of exogenous pepsin did not
      affect the activation rate of the engineered pepsinogen but accelerated
      pepsinogen activation through the bimolecular reaction. The above results
      indicated that the engineered pepsinogen exhibited, primarily, a self-activation
      mechanism and that bimolecular activation was negligible.

PMID- 9143342
TI  - Characterization of rainbow trout (Oncorhynchus mykiss) growth hormone 1 gene and
      the promoter region of growth hormone 2 gene.
AB  - Studies by Agellon et al. (Mol. Reprod. Dev. 1, 11-17) showed the presence of two
      growth hormone (rtGH1 and rtGH2) mRNA species in pituitary glands of adult
      rainbow trout (Oncorhynchus mykiss). In this study, we have detected rtGH1 and
      rtGH2 mRNAs in pituitary glands of rainbow trout from fry to 2 years of age. The
      level of rtGH1 mRNA is notably higher than that of rtGH2 mRNA in 10-day-old fry
      and 2-year-old females. These results suggest differential expression of rtGH1
      and rtGH2 genes in different sexes and developmental stages. As a step toward
      elucidating the mechanism of differential expression of both GH genes, DNA
      fragments encoding rtGH1 gene and the promoter/regulatory region of rtGH2 gene
      were isolated and characterized. Rainbow trout GH genes span approximately 4.5 kb
      and are composed of six exons and five introns. The 5'-flanking region of both
      genes contain consensus sequences for TATA boxes and several Pit-1 binding
      sequences. Consensus sequences related to the cAMP response element, thyroid
      hormone response element, retinoic acid response element, estrogen response
      element (ERE), and glucocorticoid response element are present not only in the 5'
      flanking region, but also in introns and exons in rtGH1 gene. These hormone
      response elements, except ERE, are also present in rtGH2 gene.

PMID- 9143343
TI  - Induction of ferritin synthesis in human lung epithelial cells treated with
      crocidolite asbestos.
AB  - Crocidolite asbestos is a known human carcinogen containing 27% iron by weight.
      It has previously been shown that iron was mobilized intracellularly from
      crocidolite after treatment of human lung epithelial cells (A549) and that the
      toxicity of the fibers was directly related to how much mobilized iron was in the
      < 10,000 MW (low-molecular-weight, LMW) fraction [C. C. Chao, L.G. Lund, K. R.
      Zinn, and A. E. Aust (1994) Arch. Biochem. Biophys. 314, 384-391]. The data here
      show that iron mobilization from crocidolite began immediately after treatment of
      the A549 cells and increased linearly with time. However, the synthesis of
      ferritin, an iron storage protein, did not begin until after 4 h of treatment,
      reaching a sustained maximum after 12 h. Mobilized iron was preferentially
      incorporated into the nonferritin-protein fraction up to 7 h after treatment,
      when the amount of iron mobilized was low and before significant accumulation of
      newly synthesized ferritin had occurred. This suggested that these cultured cells
      needed additional iron for synthesis of iron-requiring proteins and that iron
      mobilized from crocidolite could be utilized directly for this purpose.
      Subsequent to this, additional mobilized iron was incorporated into newly
      synthesized ferritin. Even though iron from crocidolite was incorporated into
      newly synthesized ferritin or into other proteins, the amount of iron from
      crocidolite in the LMW fraction remained constant during the 24 h. Thus, it
      appeared that synthesis of ferritin may not have fully protected the cells from
      the toxic effects of iron mobilized from crocidolite.

PMID- 9143344
TI  - Palmitoylation of muscarinic acetylcholine receptor m2 subtypes: reduction in
      their ability to activate G proteins by mutation of a putative palmitoylation
      site, cysteine 457, in the carboxyl-terminal tail.
AB  - A putative palmitoylation site, Cys457, of muscarinic acetylcholine receptor m2
      subtype (m2 receptor) was eliminated by conversion to alanine or stop codon by
      site-directed mutagenesis. The mutant m2 receptor C457A was not metabolically
      labeled with [3H] palmitic acid when expressed in Sf9 cells, whereas the wild
      type m2 receptor was labeled under the same conditions. These results confirm
      that the Cys457 is the palmitoylation site. The rate of palmitoylation was
      markedly accelerated by addition of agonist, indicating that the palmitoylation
      reaction is affected by conformational changes of the receptor induced by agonist
      binding. The m2 receptor mutants without palmitoylation were purified and
      reconstituted with G proteins into phospholipid vesicles. Both mutants were good
      substrates of G protein-coupled receptor kinase 2 and the phosphorylation was
      stimulated by agonist and G protein beta gamma subunits, as was the case for wild
      type receptors. The mutant receptors interacted with and activate Gi2 and G(o).
      However, the rate of [35S] GTP gamma S binding to Gi2 was half as much for the
      mutants as that for the wild type, and the proportion of guanine nucleotide
      sensitive high-affinity agonist binding sites was significantly less for mutants
      (42-42%) compared to wild type (62%). These results indicate that the
      palmitoylation of m2 receptors is not an absolute requirement for their
      interaction with G proteins but enhances the ability of the receptors to interact
      with G proteins.

PMID- 9143345
TI  - Sorbitol dehydrogenase from bovine lens: purification and properties.
AB  - Bovine lens sorbitol dehydrogenase (L-iditol:NAD+ 2-oxidoreductase, EC 1.1.1.14)
      (SDH) was purified to electrophoretic homogeneity (51 U/mg of protein) and
      characterized for both kinetic and some structural properties. The enzyme proves
      to be a homotetramer of 156 kDa containing one equivalent of zinc ion per
      subunit. Metal chelators such as EDTA and 1,10-phenanthroline determine a loss of
      enzyme activity which can be specifically recovered by addition of either zinc or
      manganese ions. Inactivation induced not only by metal chelators but also by
      thiol reagents is effectively prevented by the pyridine cofactor. Bovine lens SDH
      is active on polyalcohols and keto-sugars with more than three carbon atoms, and
      also requires special steric constraints for substrate recognition. Of the
      polyols, xylitol is the most effective substrate (kcat/KM of 8.1 s-1 mM-1),
      followed by sorbitol (kcat/KM of 1.59 s-1 mM-1); fructose, the most effective
      carbonyl substrate, displays a kcat/KM of only 0.9 s-1 mM-1. Analysis at the
      steady state of initial velocities as a function of the concentration of
      different substrates and cofactors and studies of product inhibition indicate for
      both fructose reduction and sorbitol oxidation a Theorell and Chance-type kinetic
      mechanism of action.

PMID- 9143346
TI  - Exendin-4 agonist and exendin(9-39)amide antagonist of the GLP-1(7-36)amide
      effects in liver and muscle.
AB  - The GLP-1 structurally related peptides exendin-4 and exendin(9-39)amide were
      found to act, in rat liver and skeletal muscle, as agonist and antagonist,
      respectively, of the GLP-1(7-36)amide effects on glucose metabolism. Thus, like
      GLP-1(7-36)amide, exendin-4 increased glycogen synthase a activity and glucose
      incorporation into glycogen in both tissues and also stimulated exogenous D
      glucose utilization and oxidation in muscle. These effects of GLP-1(7-36)amide
      and exendin-4 were inhibited by exendin(9-39)amide. Our findings provide further
      support to the proposed use of GLP-1, or exendin-4, as a tool in the treatment of
      diabetes mellitus. Thus, in addition to the well-known insulinotropic action of
      the peptides, they act both in liver and in muscle in a manner most suitable for
      restoration of glucose homeostasis, with emphasis on their positive effects upon
      glycogen synthesis in the two tissues and on the stimulation of exogenous glucose
      catabolism in muscle.

PMID- 9143347
TI  - Characterization of monoclonal antibodies recognizing different fragments of
      cartilage oligomeric matrix protein in human body fluids.
AB  - Cartilage oligomeric matrix protein (COMP) is a high-molecular-weight
      glycoprotein found at a high concentration in articular cartilage. Recent studies
      have shown that the joint fluid and serum levels of antigenic COMP, measured by
      an enzyme-linked immunosorbent assay (ELISA) which uses a polyclonal antiserum
      raised against bovine COMP, provide important information about metabolic changes
      occurring in the cartilage matrix in joint disease. In this report, we describe
      the specificity of three monoclonal antibodies (mAbs) to human COMP and their
      usefulness in quantifying antigenic COMP fragments in body fluids. Two of the
      mAbs (16-F12 and 18-G3) recognized both oligomeric and monomeric forms of COMP,
      but the third (17-C10) reacted positively only with the former. Immunoblots of
      human COMP, predigested with trypsin for up to 6 h, showed that the three mAbs
      are directed against different epitopes identified on small tryptic fragments of
      30 kDa (16-F12), 25 kDa (17-C10), and 40 kDa as well as 30 kDa (18-G3),
      respectively. The antibodies also recognized a different pattern of fragments in
      human pathological synovial fluids. This was particularly striking in the case of
      the medium size fragments (16-F12: 90 and 110 kDa; 17-C10: 70 and 90 kDa; 18-G3:
      up to five bands from 70 to 130 kDa). Competitive indirect inhibition ELISAs
      developed with mAbs 16-F12 and 17-C10 revealed further differences in the
      specificities of these antibodies. Thus, while mAb 16-F12 can be used only to
      quantify antigenic COMP in human synovial fluid and serum, mAb 17-C10 is useful
      in addition when analyzing canine and horse synovial fluid as well as canine
      serum. The results of analyses of synovial fluid samples from patients with
      osteoarthritis and rheumatoid arthritis provided preliminary evidence in support
      of the contention that measurement of the different COMP epitopes recognized by
      these mAbs in body fluids could prove useful in the clinical assessment of
      patients with joint disease.

PMID- 9143348
TI  - Lysosomal proteolysis of prosaposin, the precursor of saposins (sphingolipid
      activator proteins): its mechanism and inhibition by ganglioside.
AB  - Saposins A, B, C, and D, which are required for the enzymatic hydrolysis of
      sphingolipids by specific lysosomal hydrolases, are produced by proteolytic
      processing of their common precursor protein, prosaposin. Our previous
      observation suggested that lysosomal cathepsin D may be involved in the
      proteolysis of prosaposin. Herein we report the involvement of cathepsin D in the
      proteolytic processing of prosaposin. An antibody against human placental
      cathepsin D blocked the proteolytic activity toward prosaposin in a human
      testicular lysosomal protease mixture (glycoprotein fraction). On immunoblot
      analysis using a monoclonal antibody against human saposin C, cathepsin D showed
      a similar proteolytic pattern as that of a human testicular glycoprotein fraction
      and hydrolyzed prosaposin into products of 48 and 29 kDa. The Km and Vmax values
      were 0.9 microM and 167 nmol/h/mg, respectively. N-Terminal sequence analysis
      indicated that the 48-kDa band was a mixture of two trisaposins, including
      domains for saposins A, B, and C and saposins B, C, and D, respectively. A
      similar study also showed that the 29-kDa band contained two disaposins,
      including domains for saposins A and B and saposins C and D, respectively. By
      longer treatment with cathepsin D, disaposins were further processed into mature
      saposin A and small fragments (14.5-17.5 kDa) containing individual saposins and
      portions of interdomain sequences. These small fragments were no longer processed
      by cathepsin D, but trimmed to fragments having similar molecular sizes (10.5
      11.5 kDa) to those of mature saposins by a rat lysosome preparation. These
      findings indicated that cathepsin D is involved in the maturation of saposins but
      that, in addition to cathepsin D, other proteases appear to be involved in the
      maturation of saposin B, C, and D in lysosomes. Gangliosides, which specifically
      form complexes with prosaposin and saposins, inhibit proteolysis of prosaposin by
      cathepsin D. This finding indicates that prosaposin may be protected from
      lysosomal proteolysis by forming a complex with gangliosides in vivo.

PMID- 9143349
TI  - Characterization of cytochrome P4502E1 turnover in transfected HepG2 cells
      expressing human CYP2E1.
AB  - The aim of the present study was to characterize human CYP2E1 turnover and
      examine the possible proteolytic pathways responsible for the rapid degradation
      of CYP2E1 in a transfected HepG2 cell line expressing human CYP2E1. Two methods
      were used to study the CYP2E1 turnover; after addition of cycloheximide, the half
      life of the CYP2E1 in the intact cells was about 6 h as detected by PNP catalytic
      activity assay and immunoblot analysis of apoprotein content. CYP2E1 substrates
      or ligands such as 4-methylpyrazole, ethanol, glycerol, and dimethyl sulfoxide
      protected CYP2E1 against this rapid degradation, whereas CCl4 accelerated this
      process. The second procedure involved pulse-chase experiments after labeling
      CYP2E1 with [35S]methionine and immunoprecipitation with anti-human CYP2E1 IgG.
      The half-life of CYP2E1 was about 2.5 h, and the various substrates or ligands
      modified the turnover process within intact cells as described for the
      cycloheximide experiments. More than 20 different reagents including
      antioxidants, physiological metabolites, lysosomal inhibitors, and protease
      inhibitors were screened for possible effects on CYP2E1 proteolytic degradation.
      Dibutyryl cAMP had no effect on CYP2E1 activity or turnover. Among those reagents
      tested so far, the serine protease inhibitor 1-chloro-3-tosylamido-7-amino-2
      heptanone hydrochloride exhibited some protection against CYP2E1 degradation. To
      demonstrate whether the proteasome complex is involved in this process, Czb-Ile
      Glu(OtBu)-Ala-leucinal (PSI) as a cell penetrating aldehydic proteasome inhibitor
      and Czb-Leu-norleucinal (calpeptin inhibitor) as an aldehydic nonproteosomal
      protease inhibitor were used to examine their effect on both the normal and the
      CCl4-stimulated CYP2E1 proteolytic degradation pathways. Treatment with PSI at
      concentrations ranging from 5 to 80 microM resulted in a dose-dependent
      protection against the loss of both the normal CYP2E1 and the CCl4-modified
      CYP2E1. The maximum protection by PSI at a concentration of 80 microM after a 12
      h chase period was about 60% in cells treated with 2 mM CCl4 or 75% in cells
      without CCl4 treatment. Calpeptin inhibitor afforded little or no protection
      against CYP2E1 degradation in the absence or presence of CCl4. PSI did not
      inhibit CYP2E1 catalytic activity, suggesting that it was not a ligand for
      CYP2E1. These results indicate that human CYP2E1 has a short half-life span and
      that substrates can significantly modify its turnover rate in intact HepG2 cells.
      The proteasome proteolytic pathway may be involved in the degradation process of
      both the normal and the CCl4-modified human CYP2E1 in this model.

PMID- 9143350
TI  - Membrane fluidity and oxygen diffusion in cholesterol-enriched erythrocyte
      membrane.
AB  - This work studied the effect of cholesteryl hemisuccinate incorporation on
      membrane fluidity and on the kinetics of oxygen diffusion at different depths in
      the erythrocyte membrane. Cholesterol concentration in the membrane was expressed
      as the cholesterol-protein ratio (C/Pt). The membrane fluidity, as assessed by a
      fluorescence polarization method with diphenyl-hexatriene and 1-(4
      trimethylamino)-6-phenylhexa-1,3,5-triene, decreased as the C/Pt ratio increased.
      Time-resolved fluorescence spectroscopy of pyrene dodecanoic acid (PDA) under an
      increasing C/Pt ratio in the erythrocyte membrane revealed enhanced oxygen
      diffusion in the middle of the membrane bilayer (in which PDA was incorporated),
      which was not the case with pyrene butyric acid (PBA) incorporated in the
      internal part of the membrane surface. It has generally been accepted that
      increased membrane fluidity reduces the physical barrier to oxygen permeation.
      Such conflicting observations on oxygen permeation in the rigidified erythrocyte
      membrane could be due to variations in oxygen solubility (preferential
      partitioning) in different polarity microdomains (cholesterol and phospholipid
      partitions).

PMID- 9143351
TI  - Mg-dependent ecto-ATPase activity in Leishmania tropica.
AB  - ATPase activity has been located on the external surface of Leishmania tropica.
      Since Leishmania is known to have an ecto-acid phosphatase, in order to discard
      the possibility that the ATP hydrolysis observed was due to the acid phosphatase
      activity, the effect of pH in both activities was examined. In the pH range from
      6.8 to 8.4, in which the cells were viable, the phosphatase activity decreased,
      while the ecto-ATPase activity increased. To confirm that the observed ATP
      hydrolysis was promoted by neither phosphatase nor 5'-nucleotidase activities, a
      few inhibitors for these enzymes were tested. Vanadate and NaF strongly inhibited
      the phosphatase activity; however, no effect was observed on ATPase activity.
      Neither levamizole nor tetramizole, two specific inhibitors of alkaline
      phosphatases, inhibited this activity. The lack of response to ammonium molybdate
      indicated that 5'-nucleotidase did not contribute to the ATP hydrolysis. Also,
      the lack of inhibition of the ATP hydrolysis by high concentrations of ADP at
      nonsaturating concentrations of ATP discarded the possibility of any ATP
      diphosphohydrolase activity. The ATPase here described was stimulated by MgCl2
      but not by CaCl2. In the absence of divalent metal, a low level of ATP hydrolysis
      was observed, and CaCl2 varying from 0.1 to 10 mM did not increase the ATPase
      activity. At 5 mM ATP, half-maximal stimulation of ATP hydrolysis was obtained
      with 0.29 +/- 0.02 mM MgCl2. The apparent K(m) for Mg-ATP2- was 0.13 +/- 0.01 mM
      and free Mg2+ did not increase the ATPase activity. ATP was the best substrate
      for this enzyme. Other nucleotides such as ITP, CTP, GTP, UTP, and ADP produced
      lower reaction rates. To confirm that this Mg-dependent ATPase was an ecto
      ATPase, an impermeant inhibitor, 4,4'-diisothiocyanostylbene-2,2'-disulfonic acid
      was used. This amino/sulfhydryl-reactive reagent did inhibit the Mg-ecto-ATPase
      activity in a dose-dependent manner (I0.5 = 27.5 +/- 1.8 microM).

PMID- 9143352
TI  - Inhibition of coumarin 7-hydroxylase activity in human liver microsomes.
AB  - Nine organic solvents and 47 commonly used P450 substrates and inhibitors were
      examined for their effects on coumarin 7-hydroxylase (CYP2A6) activity in human
      liver microsomes. Of the nine organic solvents examined (final concentration 1%,
      v/v), only methanol did not inhibit the 7-hydroxylation of coumarin (0.5 to 50
      microM) by human liver microsomes. Dioxane and tetra-hydrofuran, which are
      structurally related to coumarin, were the most inhibitory solvents examined.
      Although the rates of coumarin 7-hydroxylation varied enormously among nine
      samples of human liver microsomes and cDNA-expressed CYP2A6 (Vmax = 179 to 2470
      pmol/ mg protein/min), the Km for coumarin 7-hydroxylation was fairly constant
      (ranging from 0.50 to 0.70 microM). The following chemicals caused little or no
      inhibition of CYP2A6 as defined by a Ki > 200 microM: caffeine, chlorzoxazone,
      cimetidine, dextromethorphan, diazepam, diclofenac, erythromycin,
      ethinylestradiol, ethynyltestosterone, fluconazole, furafylline, furfural,
      hexobarbital, itraconazole, mephenytoin, methimazole, metronidazole, naringenin,
      naringin, nifedipine, norfloxacin, norgestrel, orphenadrine, quinidine,
      papaverine, phenacetin, pyrimethamine, ranitidine, spironolactone,
      sulfaphenazole, sulfinpyrazone, testosterone, tolbutamide, troleandomycin, and
      warfarin. In other words, these chemicals, at a final concentration of 100
      microM, failed to inhibit CYP2A6 when the concentration of coumarin was equal to
      Km (0.50 microM). The following chemicals were classified as strong inhibitors of
      CYP2A6 (defined by Ki < 200 microM): clotrimazole, diethyldithiocarbamate,
      ellipticine, ketoconazole, 8-methoxypsoralen, 4-methylpyrazole, metyrapone,
      miconazole, alpha-naphthoflavone, nicotine, p-nitrophenol, and tranylcypromine.
      The potency with which each chemical inhibited the 7-hydroxylation of coumarin
      was independent of which sample of human liver microsomes was studied. One of the
      most potent inhibitors of coumarin 7-hydroxylase was 8-methoxypsoralen
      (methoxsalen), which was determined to be a mechanism-based inhibitor (suicide
      substrate) of CYP2A6 (k(inactivation) 0.5 min-1). With the exception of 8
      methoxypsoralen, preincubation of human liver microsomes and NADPH with the
      aforementioned inhibitors did not increase their ability to inhibit CYP2A6. The
      most potent competitive inhibitor of CYP2A6 was tranylcypromine (Ki = 0.04
      microM). Several of the chemicals that strongly inhibited CYP2A6, such as
      ketoconazole and tranylcypromine, are often used with the intention of
      selectively inhibiting human P450 enzymes other than CYP2A6. The results of this
      study underscore the need for a systematic evaluation of the specificity of
      commonly used P450 inhibitors.

PMID- 9143353
TI  - Potency comparison of peptidomimetic inhibitors against HIV-1 and HIV-2
      proteinases: design of equipotent lead compounds.
AB  - HIV-1 and HIV-2 proteinases (PR) are responsible for the processing of viral
      polyproteins, a step that is crucial for the formation of infectious virus
      particles. PR represents one of the most important targets for antiviral
      chemotherapy. Inhibitors of HIV-1 PR usually exhibit a 10- to 100-fold weaker
      affinity for HIV-2 PR. In order to design subnanomolar inhibitors for both HIV-1
      and HIV-2 PRs, we prepared a series of compounds varying in the type of scissile
      bond replacement as well as in the P1, P1', and P2' side chains. While inhibitors
      containing reduced amide, hydroxyethylamine and statine isosteres had Ki values
      in the range of 10(-10)-10(-9) M against HIV-1 PR; their activities against HIV-2
      PR were several orders of magnitude lower. Glutamic acid was identified to be the
      optimal P2' residue for both PRs. HIV-2 PR was shown to be more sensitive to P2'
      Glu-->Gln replacement. Using this data set we were able to design and prepare
      hydroxyethylene isostere containing inhibitors that were equipotent against both
      PRs.

PMID- 9143354
TI  - Structure of a cell wall mannan from the pathogenic yeast, Candida catenulata:
      assignment of 1H nuclear magnetic resonance chemical shifts of the inner alpha
      1,6-linked mannose residues substituted by a side chain.
AB  - We performed an enzyme-linked immunosorbent assay of the cell wall mannan
      purified from the pathogenic yeast, Candida catenulata, using antisera to factors
      of the genus Candida. The results suggest that mannan possesses a linear backbone
      consisting of alpha-1, 6-linked mannose residues and side chains possessing
      nonreducing terminal alpha-1,2- and alpha-1,3-linked mannose residues. The
      chemical structure of the mannan was analyzed by two-dimensional homonuclear
      Hartmann-Hahn and two-dimensional nuclear Overhauser enhancement and exchange
      spectroscopy. The sequential assignments of the cross-peaks caused by J-coupling
      and the nuclear Overhauser effect from these terminal mannose residues
      demonstrate that the H1 signal of an inner alpha-1,6-linked mannose residue
      substituted by an alpha-oligomannosyl side chain or a single mannose through the
      C-2 position in an alpha-anomer configuration undergoes a significant downfield
      shift (delta delta = 0.16 or 0.19 ppm, respectively) compared with that of
      unsubstituted residues. We therefore propose the exact overall structure of the
      antigenic mannan obtained from C. catenulata. The assignment data in the present
      study are useful for the determination of the exact overall structure of various
      yeast mannans using the two-dimensional nuclear magnetic resonance analysis
      without the need for harsh procedures.

PMID- 9143355
TI  - Salt concentration determines 1,25-dihydroxyvitamin D3 dependency of vitamin D
      receptor-retinoid X receptor--vitamin D-responsive element complex formation.
AB  - The electrophoretic mobility shift assay was used to determine in vitro formation
      of the vitamin D receptor-retinoid X receptor beta (VDR-RXR beta) heterodimer
      complex on vitamin D-response elements (VDREs) from rat osteocalcin, mouse
      osteopontin, rat 25-hydroxyvitamin D3 24-hydroxylase, and human parathyroid
      hormone (PTH) genes. Baculovirus-expressed rat VDR was used as VDR and the
      binding reactions were performed at salt concentrations ranging from 50 to 170 mM
      KCI. Without ligand, optimum complex formation was observed at 50 mM KCI and
      markedly decreased with increasing KCI for all VDREs. In the presence of 1,25
      dihydroxyvitamin D3, optimum complex formation occurred between 110 and 130 mM
      KCI for positive (enhancer) VDREs. At low salt concentrations (50-70 mM KCI),
      1,25-dihydroxyvitamin D3 did not increase complex formation and actually caused a
      slight decrease. However, above 90 mM KCI, 1,25-dihydroxy-vitamin D3 markedly
      increased complex formation and at 150-170 mM KCI, a concentration that
      presumably mimics physiologic nuclear levels, 1,25-dihydroxy-vitamin D3 appeared
      to be required for complex formation. With the suppressive cis-acting sequence,
      i.e., PTH-VDRE, optimum detection of VDR complexes in the presence of 1,25
      dihydroxyvitamin D3 occurred at a lower salt concentration (90-110 mM KCI).
      Moreover, no specific complexes were formed at high salt concentrations, even
      when 1,25-dihydroxyvitamin D3 was added. Thus, when analyzing an effect of ligand
      on VDR-RXR-VDRE complex formation, it is essential that the reaction be carried
      out with a range of salt concentrations. Further, 1,25-dihydroxyvitamin D3
      appears to be required for formation of the VDR-RXR beta-VDRE complex at salt
      concentrations approaching physiological.

PMID- 9143356
TI  - Purification, characterization and partial primary structure of morphine 6
      dehydrogenase from rabbit liver cytosol.
AB  - Morphinone, a toxic metabolite, was formed from morphine by NAD(P)-dependent
      morphine 6-dehydrogenase(s) in both the cytosol and microsomal fractions of the
      rabbit liver at pH 7.4. The enzyme activity in the cytosol fraction was about
      twice that in the microsomal fraction and NAD served as the preferred cofactor in
      both fractions. The enzyme in the cytosol fraction was purified to a homogeneous
      protein by the use of various chromatographic techniques. The enzyme is a
      monomeric protein with a molecular weight of 36,000 and an isoelectric point of
      6.4. The enzyme had a dual cofactor specificity but NAD was more efficiently
      utilized than NADP. With NAD, the enzyme showed an optimal pH of 9.4, and the Km
      and Vmax values toward morphine were 0.72 mM and 0.59 unit/mg protein,
      respectively. The enzyme also exhibited a significant activity for morphine
      analogs having an unsaturated bond at C-7,8 (codeine, ethylmorphine, and
      normorphine), alicyclic alcohols (3-hydroxyhexobarbital, 1-indanol, and
      cyclohexene-2-ol) and benzenedihydrodiol. In the reverse reaction, the enzyme
      exhibited highly restricted specificity for o-quinones. Sulfhydryl re-agents and
      quercetin inhibited the enzyme but pyrazole, barbital, and indomethacin had
      little effect on the enzyme activity. Androstanes, lithocholic acid, and
      estradiol potently inhibited the enzyme in a competitive manner toward morphine
      binding. The partial amino acid sequence of the random peptides obtained by the
      proteolytic digestion of the enzyme, which comprised about 40% of the whole
      protein, revealed a significant homology to the corresponding regions in the
      members of the aldo-keto reductase family. These results therefore indicate that
      the present enzyme is a new and unique member of the aldo-keto reductase family.

PMID- 9143357
TI  - A differential scanning calorimetric study of Newcastle disease virus:
      identification of proteins involved in thermal transitions.
AB  - The irreversible thermal denaturation of Newcastle disease virus was investigated
      using different techniques including high-sensitivity differential scanning
      calorimetry, thermal gel analysis intrinsic fluorescence, and neuraminidase
      activity assays. Application of a successive annealing procedure to the scanning
      calorimetric endotherm of Newcastle disease virus furnished four elementary
      thermal transitions below the overall endotherm; these were further identified as
      coming from the denaturation of each viral protein. The shape of these
      transitions, as well as their scanrate dependence, was explained by assuming that
      thermal denaturation takes place according to the kinetic scheme N-->(k)D, where
      k is a first-order kinetic constant that changes with temperature, as given by
      the Arrhenius equation; N is the native state; and D is the denatured state. On
      the basis of this model, activation energy values were calculated. The data
      obtained with the other methods used in this work support the proposed two-state
      kinetic model.

PMID- 9143358
TI  - The human glycinamide ribonucleotide transformylase domain: purification,
      characterization, and kinetic mechanism.
AB  - Glycinamide ribonucleotide transformylase catalyzes the third reaction of de novo
      purine biosynthesis, namely, the conversion of glycinamide ribonucleotide to N
      formylglycinamide ribonucleotide, with concomitant conversion of 10
      formyltetrahydrofolate to tetrahydrofolate. This activity has been shown to be a
      target for cancer chemotherapy, which has generated renewed interest in both the
      enzyme and the pathway. Moreover, in higher eukaryotes this activity constitutes
      the C-terminal domain of a monomeric protein which also catalyzes two additional
      reactions of de novo purine biosynthesis. In this study, the human glycinamide
      ribonucleotide transformylase domain has been expressed to high levels in
      Escherichia coli and purified to homogeneity. Our improved expression
      purification system produces the desired activity exclusively in a soluble form
      and in higher abundance than previously achieved. The kinetic constants have been
      determined and the kinetic mechanism has been established as ordered-sequential,
      with the folate substrate binding first. The correspondence of these data to
      those obtained for the glycinamide ribonucleotide transformylase activity of the
      mammalian trifunctional enzyme indicates that the recombinant enzyme is fully
      functional.

PMID- 9143359
TI  - Expression of CYP71B7, a cytochrome P450 expressed sequence Tag from Arabidopsis
      thaliana.
AB  - The systematic sequencing of anonymous cDNA clones (expressed sequence tags or
      ESTs) from the plant Arabidopsis thaliana has identified a number of cDNAs with
      similarity to known cytochrome P450 sequences. The partial sequence of one of
      these cDNAs, 5G6, indicated that it was likely to encode a full-length cytochrome
      P450 monooxygenase (cyt P450) sequence. In this paper we describe the complete
      sequence of this clone, which has been designated CYP71B7 in accordance with the
      nomenclature for the cyt P450 gene superfamily. The cDNA was used to determine
      the pattern of expression of the corresponding gene in A. thaliana. Northern
      hybridization analysis indicated that maximal expression of CYP71B7 occurred in
      rosette leaves. Weaker hybridizing bands were also detected by Northern analysis
      of RNA from roots, leaves, flowers, and siliques. No expression could be detected
      in stem tissue. Southern analysis indicated that the CYP71B7 gene was likely to
      exist as a single copy in the genome of A. thaliana. CYP71B7 was expressed
      episomally in yeast, and microsomes prepared from transgenic yeast exhibited a
      carbon monoxide difference spectrum characteristic of cyt P450. Microsomes from
      yeast expressing CYP71B7 were assayed for enzymatic activity with synthetic model
      cyt P450 substrates. Microsomes from yeast cells expressing CYP71B7 or those from
      control cells exhibited no detectable NADPH-supported 7-ethoxycoumarin or 7
      ethoxyresorufin deethylase activities. However, in the presence of cumene
      hydroperoxide, activity was observed with microsomes from cells expressing
      CYP71B7 with 7-ethoxycoumarin as substrate. Organic hydroperoxides are well known
      to support cyt P450 catalysis in the absence of electrons from NADPH. The yeast
      microsomes contained high levels of endogenous NADPH-ferricytochrome P450
      reductase (CPR) activity. The data suggest that this A. thaliana cyt P450,
      although expressed in an active form, is incapable of accepting electrons from
      the endogenous yeast CPR protein.

PMID- 9143360
TI  - Fatty acid binding protein: stimulation of microsomal phosphatidic acid
      formation.
AB  - The effect of fatty acid binding proteins (FABPs) on two key steps of microsomal
      phosphatidic acid formation was examined. Rat liver microsomes were purified by
      size-exclusion chromatography to remove endogenous cytosolic fatty acid and fatty
      acyl-CoA binding proteins while recombinant FABPs were used to avoid cross
      contamination with such proteins from native tissue. Neither rat liver (L-FABP)
      nor rat intestinal fatty acid binding protein (I-FABP) stimulated liver
      microsomal fatty acyl-CoA synthase. In contrast, L-FABP and I-FABP enhanced
      microsomal conversion of [14C]oleoyl-CoA and glycerol 3-phosphate to
      [14C]phosphatidic acid by 18- and 7-fold, respectively. The mechanism for this
      stimulation, especially by I-FABP, is not known. However, several observations
      presented here suggest that, like L-FABP, I-FABP may interact with fatty acyl-CoA
      and thereby stimulate enzyme activity. First, I-FABP decreased microsomal
      membrane-bound oleoyl-CoA. Second, oleoyl-CoA displaced I-FABP bound fluorescent
      fatty acid, cis-parinaric acid, with Ki of 5.3 microM and 1.1 sites. Third,
      oleoyl-CoA decreased I-FABP tryptophan fluorescence with a Kd of 4.2 microM.
      Fourth, oleoyl-CoA red shifted emission spectra of acrylodated I-FABP, a
      sensitive marker of I-FABP interactions with ligands. In summary, the results
      demonstrate for the first time that both L-FABP and I-FABP stimulate liver
      microsomal phosphatidic acid formation by enhancing synthesis of phosphatidate
      from fatty acyl-CoA and glycerol 3-phosphate.

PMID- 9143361
TI  - The effects of the ergosteroid 7-oxo-dehydroepiandrosterone on mitochondrial
      membrane potential: possible relationship to thermogenesis.
AB  - Administered 3 beta-hydroxyandrost-5-ene-7,17-dione (7-oxo-DHEA) is more
      effective than 3 beta-hydroxyandrost-5-en-7-one (DHEA) as an inducer of liver
      mitochondrial sn-glycerol-3-phosphate dehydrogenase and cytosolic malic enzyme in
      rats. Like DHEA, the 7-oxo metabolite enhances liver catalase, fatty acylCoA
      oxidase, cytosolic sn-glycerol-3-phosphate dehydrogenase, mitochondrial substrate
      oxidation rate, and the reconstructed sn-glycerol 3-phosphate shuttle. The
      mitochondrial adenine nucleotide carrier is diminished by thyroidectomy and is
      restored to normal activity by administering 7-oxo-DHEA. The relationship between
      respiratory rate and proton motive force across the mitochondrial membrane was
      measured in the nonphosphorylating state. When treated with increasing
      concentrations of respiratory inhibitors liver mitochondria from rats treated
      with 7-oxo-DHEA or thyroid hormones show a more rapid decline of membrane
      potential than do normal liver mitochondria. Thus 7-oxo-DHEA induces an increased
      proton leak or slip as has been reported for the thyroid hormone by M.D. Brand
      [(1990) Biochem. Biophys. Acta 1018, 128-133]. This process may contribute to the
      enhanced thermogenesis caused by ergosteroids as well as by thyroid hormones.

PMID- 9143362
TI  - Inhibition of GTP gamma S-dependent phospholipase D and Rho membrane association
      by calphostin is independent of protein kinase C catalytic activity.
AB  - We studied the relationships between the activation of phospholipase D (PLD) by
      guanine nucleotides and phorbol esters in permeabilized U937 promonocytes and in
      solubilized extracts prepared from U937 cell membranes. Treatment of
      permeabilized cells with phorbol myristate acetate (PMA) strongly potentiated GTP
      gamma S-dependent PLD activity at free Ca2+ < 100 nM. In the absence of GTP gamma
      S, PMA stimulated only minor PLD activity. This suggested synergistic interaction
      between regulatory G-proteins and a protein kinase C (PKC) family kinase. The
      potential role of PKC was evaluated by testing two mechanistically distinct PKC
      inhibitors, bisindolylmaleimide (BIM) and calphostin. BIM inhibits PKC enzymes
      via competition with ATP for binding to the catalytic domain, while calphostin
      competes with PMA or diglyceride for binding to the regulatory domain. The
      ability of PMA to potentiate the GTP gamma S-dependent PLD was not inhibited by
      BIM. In contrast, calphostin strongly inhibited the GTP gamma S-dependent PLD
      activity, both in the presence and absence of PMA as a potentiating agent.
      Calphostin also produced complete inhibition of a GTP gamma S-dependent PLD
      activity, present in solubilized membrane extracts, which was assayed using
      phospholipid vesicles of defined composition. Treatment of reconstituted
      membrane/cytosol mixtures with calphostin also produced complete inhibition of
      the GTP gamma S-induced translocation of Rho A from cytosol to membrane. In
      contrast to its effects on the U937 cell PLD, calphostin did not inhibit the
      activity of purified PLD from cabbage. These results suggest that the assembly of
      active RhoA/PLD signaling complexes on membranes involves a phorbol
      ester/calphostin-binding protein, but is not dependent on PKC-type catalytic
      activity.

PMID- 9143363
TI  - Effect of acetaldehyde on Sp1 binding and activation of the mouse alpha 2(I)
      collagen promoter.
AB  - Acetaldehyde activates the mouse alpha 2(I) collagen promoter and this effect is
      mediated in part by increased binding of nuclear factor I (NF-I). Additional
      mechanisms may exist since deletions in the promoter upstream to the NF-I binding
      site prevented enhancement by acetaldehyde. Three adjacent areas of binding by
      nuclear proteins from activated hepatic stellate cells were identified at -568 to
      -554 (region 1), -542 to -518 (region 2), and -473 to -453 (region 3) of the
      promoter using DNase I protection analyses. Multiple DNA-protein complexes were
      formed in electrophoretic mobility shift assays with oligonucleotide probes
      specifying the three regions. Sp1 and NF-1 bound to all three regions, while Sp3
      bound to region 2. Acetaldehyde decreased nuclear protein binding to all three
      regions. Mutations of regions 1, 2, and 3 reduced basal activity of the promoter
      and inhibited acetaldehyde stimulation in transfected stellate cells.
      Acetaldehyde inhibited the stimulatory effect of the Sp1 vector pPacSp1 on the
      promoter in transfected Drosophila cells. In conclusion, three regions of Sp1
      binding were identified and are required for optimal activity of the alpha 2(I)
      collagen promoter. Sp1 is required for basal activity of the alpha 2(I) collagen
      promoter; however, the enhancing effect of acetaldehyde on the promoter is not
      mediated by Sp1.

PMID- 9143364
TI  - Purification and characterization of hepatic inorganic pyrophosphatase
      hydrolyzing imidodiphosphate.
AB  - A 56-kDa inorganic pyrophosphatase consisting of 33-kDa subunits was purified
      from bovine liver almost to homogeneity. This hydrolase required divalent cations
      such as MgCl2, CoCl2, and MnCl2 to hydrolyze PPi and was insensitive to 2 mM
      sodium fluoride. The purified hydrolase released 2.1 mumol Pi from PPi per minute
      per milligram of protein in the presence of 1 mM MgCl2, and the Km for PPi was
      0.14 mM. It also hydrolyzed imidodiphosphate to yield Pi and ammonia even in the
      absence of a divalent cation. The purified hydrolase liberated 2.2 mumol Pi from
      imidodiphosphate per minute per milligram of protein and the Km for
      imidodiphosphate was 0.12 mM. Addition of 80 microM MgCl2, CoCl2, or MnCl2 to the
      reaction mixture increased the hydrolysis rate of imidodiphosphate by 1.5-, 2.0-,
      and 3.4-fold, respectively. In the absence of divalent cations, the enzymatic
      hydrolysis of imidodiphosphate was inhibited competitively by PPi (Ki = 0.13 mM).
      Moreover, one-half of the maximal hydrolysis of imidodiphosphate was inhibited by
      10 microM trans-1,2-diaminocyclohexane N,N,N',N'-tetraacetic acid or 45 microM p
      chloromercuriphenyl sulfonate. When the hydrolase was treated with heat or SDS,
      two activities capable of hydrolyzing PPi and imidodiphosphate gave similar
      inactivation profiles, indicating that one hydrolase participated in the
      hydrolysis of both substrates.

PMID- 9143365
TI  - Inhibition of P-glycoprotein ATPase activity by procedures involving trapping of
      nucleotide in catalytic sites.
AB  - Fluoroaluminate in combination with nucleotide inhibited ATPase activity of P
      glycoprotein (Pgp) in plasma membranes and in pure reconstituted form. Low
      nucleotide concentrations were effective, e.g., half-maximal inhibition was
      obtained with 10 microM MgATP. With MgATP or MgADP, reactivation occurred with
      t1/2 = 7 min at 37 degrees C. With 8-azido-ATP, UV irradiation of inhibited Pgp
      gave specific photolabeling of both nucleotide sites. Fluoroaluminate therefore
      provides a valuable tool for functional and structural characterization of P
      glycoprotein and probably of other ABC transporters. 2-Azido-ATP, in combination
      with vanadate, fluoroaluminate, or beryllium fluoride, inhibited Pgp ATPase
      activity. Low concentrations of 2-azido-ATP were effective. However, after UV
      irradiation of the inhibited Pgp species, in no case was there evidence of
      covalent labeling of nucleotide sites. Therefore in the Pgp catalytic sites,
      under conditions of nucleotide trapping, there is no suitable amino acid side
      chain adjacent to the photoactivated 2-position of bound 2-azido-nucleotide, and
      8-azido-ATP is the preferred photolabeling analog.

PMID- 9143366
TI  - Lamprey fructose-1,6-bisphosphate aldolase: characterization of the muscle-type
      and non-muscle-type isozymes.
AB  - To study evolutionary aspects of fructose-1,6-bisphosphate (Fru-1,6-P2) aldolase
      during deuterostomian evolution, we have purified and characterized aldolases
      from the muscle and liver of lamprey (Entosphenus japonicus). Aldolase from the
      skeletal muscle and liver was identified to be the muscle-type isozyme and the
      non-muscle-type isozyme that was encoded by cDNAs M8 and L3, respectively, as
      described previously (Zhang, R., Yatsuki, H., Kusakabe, T., Iwabe, Miyata, T.,
      Imai, T., Yoshida, M., and Hori, K., J. Biochem. 117, 545-553, 1995). The muscle
      type isozyme has properties similar to vertebrate aldolase A, while the non
      muscle-type isozyme shows a similarity to bacterial class I aldolase and
      vertebrate aldolase C but not to aldolase B, the liver-type aldolase, in terms of
      kinetic parameters: the Kcat values toward Fru-1,6-P2 and Fru-1-P, the Fru-1,6
      P2/Fru-1-P activity ratio, and the Km values toward these substrates. The two
      enzymes have tetrameric forms with a molecular mass of approximately 160,000 and
      have similar pH optimum. The muscle-type and non-muscle-type isozymes from the
      tissues show different electrophoretic mobility; the muscle-type isozyme moves
      much faster than the non-muscle-type isozyme toward anodic side. The recombinant
      muscle-type and non-muscle-type aldolases gave similar characteristics as those
      from the tissues. The results presented in this paper, together with the data
      presented in the previous paper, strongly suggest that in lamprey it is possible
      to have two types of aldolase isozymes rather than one or three isozymes.

PMID- 9143367
TI  - Presence of glycerol masks the effects of phosphorylation on the catalytic
      efficiency of cytosolic phospholipase A2.
AB  - Cytosolic phospholipase A2 catalyzes the selective release of arachidonic acid
      from the sn-2 position of phospholipids and is believed to play a key cellular
      role in the generation of arachidonic acid. The enzymatic activity of cPLA2 is
      affected by several mechanisms, including substrate presentation and the
      phosphorylation state of the enzyme. Using covesicles of 1-palmitoy1-2
      arachidonoyl-[arachidonoyl-1-14C]-8n-glycero-3 -phosphocholine and 1,2
      dimyristoyl-phosphatidylmethanol as substrate, the effects of phosphorylation on
      the interfacial binding and catalytic constants were investigated. Phosphorylated
      and dephosphorylated enzyme forms were shown to have identical values of 2.6
      microM for KMapp, an equilibrium dissociation constant which consists of the
      intrinsic dissociation constant from the lipid/water interface (Ks) and the
      dissociation constant for phospholipid from the active site (KM*). Moreover, the
      values of KM* for phosphorylated and dephosphorylated enzyme did not differ
      significantly (0.4 +/- 0.1 and 0.2 +/- 0.1, respectively). However,
      dephosphorylation of the enzyme reduced the value of kcat by 39%. The
      phosphorylation state of the enzyme had no effect on either the cooperativity
      shown by this enzyme or the thermal stability of the enzyme. Surprisingly, the
      presence of glycerol (4 M) masks the effect of phosphorylation on kcat. Instead,
      glycerol increased the value of kcat by 440% for the phosphorylated enzyme and by
      760% for the dephosphorylated form. Moreover, addition of glycerol had only small
      effects on KMapp. the increase in the kcat upon addition of glycerol results from
      a substantial decrease in the activation energy from 29.4 to 14.8 kcal. mol-1. To
      determine whether the effects of phosphorylation of the enzyme or addition of
      glycerol are unique to this artificial substrate, membranes from U937 cells were
      isolated and used as substrate. With these membranes, the dephosphorylated enzyme
      was only 21% less active than the phosphorylated enzyme. In the presence of
      glycerol, there was no detectable difference the two enzyme forms, and the rate
      of hydrolysis was increased by 300-390% over that measured in the absence of
      glycerol. These results suggest that the catalytic efficiency of the
      phosphorylated enzyme is not particularly relevant to its activation in vivo.
      Moreover, it may be that glycerol is mimicking the effect of some unidentified
      factor which greatly enhances the catalytic efficiency of the enzyme.

PMID- 9143368
TI  - Effect of thiol status on nitric oxide metabolism in the circulation.
AB  - To elucidate the dynamics of nitric oxide (NO) metabolism in the circulation and
      its relationship with glutathione metabolism, formation of nitrosylhemoglobin (NO
      Hb), S-nitrosothiols (RSNO), and nitrite+nitrate (NOx) was determined in blood
      samples from normal rats and animals that were treated with a loading dose of GSH
      or L-buthionine-[S,R]-sulfoximine (BSO), a specific inhibitor of GSH synthesis.
      When incubated in vitro with 0.2 mM NOC7, an NO donor, NO-Hb levels increased
      rapidly, peaked at 10 min, and decreased thereafter with a half-life of 35 min in
      blood samples from control, BSO-treated, or GSH-loaded animals. Levels of low
      molecular-weight RSNO in plasma samples from the three animal groups also
      increased transiently, peaked at 10 min, and decreased thereafter. However, the
      amount of RSNO formed in GSH-loaded rat plasma was significantly greater than in
      control and BSO-treated animals. Plasma levels of NOx rapidly and similarly
      increased in all animal groups. Intravenously injected NOC7 also generated NO-Hb
      in circulating erythrocytes. In control animals, blood levels of NO-Hb increased
      maximally at 30 min and decreased thereafter with a half-life of 100 min. NO-Hb
      formed in the GSH-loaded group was significantly lower than in the control group.
      In contrast, the rate of NO-Hb formation was significantly higher with the BSO
      treated group than with the control group. Although NOC7 did not affect the
      plasma levels of low-molecular-weight RSNO in plasma of both control and BSO
      treated groups, it significantly increased RSNO in the GSH-loaded group. Thirty
      minutes after administration of NOC7, about 20% of the dose was recovered as
      plasma NOx in all animal groups. These results suggested that GSH status in
      animals might affect the metabolism of NO.

PMID- 9143369
TI  - The canine sodium/myo-inositol cotransporter gene: structural organization and
      characterization of the promoter.
AB  - The sodium/myo-inositol cotransporter (SMIT) is a plasma membrane protein
      catalyzing transfer of myo-inositol into cells against a considerable
      concentration gradient using the electrochemical potential of sodium across the
      cell membrane. Transcription of the SMIT gene is markedly stimulated when cells
      are exposed to a hypertonic environment resulting in increased abundance of SMIT
      mRNA and increased SMIT activity. The increased accumulation of myo-inositol
      protects cells from the deleterious effects of hypertonicity. In an effort toward
      understanding transcriptional regulation, we cloned canine genomic DNA fragments
      containing the SMIT gene. The gene is 37 kb in size consisting of 2 exons and a
      large intron of 25 kb. The entire open reading frame is in the second exon. The
      promoter of the gene is highly active due to a GC-rich sequence. Ribonuclease
      protection assay using a riboprobe complementary to the 5' end of the gene
      confirmed that the promoter of the gene is stimulated by hypertonicity. The
      promoters and regulatory sequences of the SMIT gene and the betaine transporter
      gene, another gene regulated by hypertonicity, appear to be different.

PMID- 9143370
TI  - Autoimmunity in myocarditis: relevance of animal models.
AB  - Infections (viruses, bacteria, protozoa, fungi) are major etiological factors
      causing clinical myocarditis and dilated cardiomyopathy. In many patients and
      symptom-free relatives antibodies and T cells reactive to heart antigens are
      detected, which implies that autoimmunity is probably a major pathogenic
      mechanism of cardiac injury. Animal models have been established to elucidate how
      infections initiate autoimmunity and how autoimmune mediators cause death or
      transient dysfunction of myocytes. Two major types of experimental models are
      discussed: adjuvant-induced myocarditis, in which animals are given multiple
      immunizations of heart proteins (myosin, adenine nucleotide translocator); and
      virus-induced myocarditis, in which animals are infected with the viruses
      predominantly associated with the human disease.

PMID- 9143371
TI  - New insights into the pathogenesis and treatment of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic multisystemic inflammatory disease with
      autoimmune features, and of unknown cause, associated with characteristic joint
      deformities and increased mortality rate. The pathogenesis of this serious
      disease seems to be multifactorial, where several cytokines, particularly
      interleukin-1 and tumor necrosis factor-alpha, are strongly involved in the
      induction and perpetuation of the chronic inflammatory process of the joints in
      RA and in the systemic manifestations of the disease. Other factors, such as
      reactive oxygen species and metalloproteinases, may also participate in the
      destruction of the rheumatoid joint. Current treatments of RA are inadequate in
      that they only partially control established RA, and despite optimal use of
      current antirheumatic agents, the outcome of many patients with RA consists of
      pain, severe functional decline, and premature death. The gloomy recent data
      regarding the prognosis of RA with the use of the current treatments stress the
      need for new therapeutic regimens with the ability to effectively control the
      inflammatory process in the rheumatoid joint and to induce long-term remission or
      even cure. Controlling the production and the activity of the factors involved in
      the pathogenesis of the disease represents the major therapeutic goal. Since
      several factors are involved in the pathogenesis of RA, neutralizing one or some
      of these factors may be of only limited benefit. In this regard, interleukin-4
      may be a very promising agent for an effective treatment of RA, because this
      cytokine is not limited by its inhibitory effects to a single factor, but rather
      it inhibits most of the main factors involved in the pathogenesis of the disease.
      Although recent data strongly support this approach with interleukin-4,
      controlled long-term clinical trails should be undertaken in order to prove the
      validity and the effectiveness of this promising approach.

PMID- 9143372
TI  - IL-10 suppresses experimental autoimmune neuritis and down-regulates TH1-type
      immune responses.
AB  - Experimental autoimmune neuritis (EAN) is a CD4+ T cell-mediated monophasic
      inflammatory disorder of the peripheral nervous system (PNS). Cellular
      mechanisms, including macrophage and T cell infiltration, and cytokines like IFN
      gamma and TNF-alpha are intimately involved in the pathogenesis of EAN.
      Interleukin 10 (IL-10) is a TH2-type cytokine that suppresses monocyte and TH1
      cell functions. We examined the effect of recombinant human IL-10 (rHuIL-10) in
      EAN. When administered from the start of immunization with bovine peripheral
      myelin emulsified in Freund's complete adjuvant, IL-10 effectively suppressed and
      shortened clinical EAN. Even when given after Day 12 post immunization (pi) after
      clinical EAN had been established, IL-10 also effectively suppressed the severity
      of EAN. Pheripheral nerve myelin antigen-reactive IFN-gamma-secreting TH1-like
      cells were decreased in lymph nodes from IL-10-treated compared to control EAN
      rats. PNS autoantigen-induced T cell proliferation and B cell responses were not
      affected. P2 protein-reactive IFN-gamma, TNF-alpha, IL-1 beta, and IL-6 mRNA
      expressing lymph node cells were also downregulated in IL-10-treated compared to
      control EAN rats at Day 14 and 26 pi, while P2-reactive IL-4 mRNA-expressing
      cells were upregulated throughout treatment. Also, in IL-10-treated EAN rats,
      upregulated anti-P2 IgG1 and downregulated IgG2a were observed. Our results
      clearly show that rHuIL-10 can suppress clinical EAN, and this suppression is
      associated with downregulation of TH1 responses and macrophage function and
      upregulated TH2 responses.

PMID- 9143373
TI  - Murine strain differences in response to mercuric chloride: antinucleolar
      antibodies production does not correlate with renal immune complex deposition.
AB  - Mercuric chloride (HgCl2) induces the production of antinucleolar antibodies
      (ANucA) in susceptible strains of mice. Responder strains bearing the H-2(5)
      haplotype as well as several ANucA resistant strains have been shown to develop
      renal immune complex deposits after HgCl2 treatment. Sera obtained throughout 12
      to 16 weeks of HgCl2 treatment from mice of four ANucA responder strains
      (A.SW/SnJ, A.CA/SnJ, DBA/1J, and P/J) and one ANucA-resistant strain
      (C57BL/10SnJ) were examined for ANucA production. Terminal sera were also tested
      for the presence of anti-glomerular basement membrane antibodies, and the kidneys
      were examined for the deposition of IgG and C3. Only one strain, A.SW, developed
      significant deposits of IgG in the renal glomeruli, although all four responder
      strains exhibited similar ANucA induction/production profiles. The differences
      seen by direct immunofluorescence assay (IFA) in renal immune complex deposition
      between the A.SW and histocompatibility congenic A.CA mice were corroborated by
      individually eluting and then quantitating the deposited IgG from renal tissues
      of Hg-treated A.SW and A.CA mice as well as control A.SW mice. The average amount
      of IgG eluted from A.SW renal tissue was significantly greater than that eluted
      from either A.CA or control A.SW renal tissues. All eluates from Hg-treated
      animals gave only a nucleolar fluorescence pattern when assayed by indirect IFA
      against a panel of rat organ tissues. In summary, no correlation was found
      between ANucA production and renal IgG deposition in response to treatment with
      HgCl2.

PMID- 9143374
TI  - Antibody-directed natural cytotoxicity results in enhanced killing of HIV gp120
      coated CEMNKR cells.
AB  - Cellular cytotoxicity may be an important defense in the control of HIV
      progression. In the present study antibodies were attached to peripheral blood
      mononuclear cells (PBMC) by exposing them to polyethylene glycol and phthalate
      oil in the presence of HIV human hyperimmune IVIG (HIVIG). The attachment
      procedure is known as "franking" and the resultant cytotoxicity is termed
      "antibody-directed." The majority of the cells that are franked with attached
      HIVIG are CD16+ (Fc gamma RIII), placing them in the natural killer cell
      population. Franking increased the cytotoxicity of PBMC from both healthy
      controls and HIV-seropositive patients approximately fourfold compared to
      conventional antibody-dependent cellular cytotoxicity using CEM cells coated with
      HIV gp120 antigen as targets. Use of anti-HIV monoclonal antibodies for franking
      was less efficient than polyclonal HIVIG. The HIVIG-franked PBMC suppressed p24
      production of in vitro HIV IIIb-infected human PBMC. The ability of HIVIG to
      enhance and direct cytotoxicity to HIV targets may suggest a new therapeutic
      approach to HIV control.

PMID- 9143375
TI  - Inhibition of Fc gamma R-dependent functions by N
      formylmethionylleucylphenylalanine in human neutrophils.
AB  - Human polymorphonuclear neutrophils (PMN) participate in different cellular
      functions, including phagocytosis, antibody-dependent cell-mediated cytotoxicity
      (ADCC), and release of reactive oxygen intermediates. Each of these functions can
      be triggered by receptors for the Fc portion of IgG molecules (Fc gamma R).
      Normal resting neutrophils possess Fc gamma RII and Fc gamma RIIIB receptors.
      They also have specific membrane receptors for formylated peptides such as the
      prototype N-formylmethionylleucylphenylalanine (FMLP). In this report, we present
      evidence that preincubation of PMN with FMLP inhibits different PMN Fc gamma R
      dependent functions such as phagocytosis, ADCC, and immune complex-dependent
      cytotoxicity. These inhibitory effects can be explained, at least in part, by
      downregulation of both Fc gamma RII and Fc gamma RIII. Unexpectedly,
      preincubation of FMLP with PMN was not necessary for ADCC inhibition. Taking into
      account that the FMLP-dependent Fc gamma R downregulation is not observed before
      30 min of incubation, and the onset of ADCC occurs rapidly (seconds), it is
      possible that FMLP can modify this function by altering early intracellular
      events.

PMID- 9143377
TI  - An in situ quantitative immunohistochemical study of cytokines and IL-2R+ in
      chronic human chagasic myocarditis: correlation with the presence of myocardial
      Trypanosoma cruzi antigens.
AB  - Inflammatory cells positive for the cytokines IL-2, IL-4, IL-6, TNF-alpha, and
      IFN-gamma and for IL-2R, as well as CD8+ and CD4+ T cells and B cells were
      quantified using an immunoperoxidase technique in 25 fresh myocardial fragments
      from patients presenting with chronic chagasic cardiomyopathy. The presence of
      Trypanosoma cruzi antigens (Ags) in the myocardium was also investigated. The
      cases were grouped into group A (no Ag), group B (scarce extramyocardial fiber
      Ags), and group C (intramyocardial pseudocysts and extramyocardial fiber Ags). IL
      2 was detected in very few cells (0.30 +/- 0.40 positive cells/hpf), suggesting
      immunological imbalance in chronic chagasic patients. IFN-gamma+ was the cytokine
      most frequently demonstrated (7.52 +/- 5.87 positive cells/hpf) and there was a
      good correlation between the number of IFN-gamma+ cells and CD8+ T cells in group
      A. IL-4+ cells were present in higher numbers in group C (2.78 +/- 1.49 positive
      cells/hpf). TNF-alpha+ (1.59 +/- 1.68 positive cells/hpf) and IL-6+ (2.76 +/-
      2.32 positive cells/hpf) cells were present in moderate numbers. Fewer B cells
      were present, not related with the intensity of T. cruzi Ags. These results
      suggest that cytokines, as they occur in other infectious diseases, play a
      fundamental role in the control of T. cruzi in chronic human chagasic disease. A
      fatal outcome seems to be associated with the increased production of cytokines
      derived from the Th2 subpopulation of the CD4+ T cells.

PMID- 9143376
TI  - Modulation of bovine leukemia virus-associated spontaneous lymphocyte
      proliferation by monoclonal antibodies to lymphocyte surface molecules.
AB  - Both human T lymphotropic virus (HTLV) and bovine leukemia virus (BLV) infections
      are characterized by in vitro proliferation of peripheral blood lymphocytes in
      the absence of exogenous antigens or mitogens. Differential expression of
      lymphocyte surface molecules in HTLV and BLV infection suggests that lymphocyte
      dysregulation may involve signaling through surface molecules involved in immune
      regulation. We examined the expression of adhesion and major histocompatibility
      (MHC) molecules on circulating lymphocytes from BLV-infected cows with persistent
      lymphocytosis and the ability of monoclonal antibodies to these molecules to
      modulate spontaneous lymphocyte proliferation. The integrin molecule, CD11c, and
      both MHC class I and MHC class II molecules were upregulated on B and T
      lymphocytes from PL cows. Anti-CD11c antibody was stimulatory to lymphocyte
      proliferation regardless of BLV status and had a greater stimulatory effect on
      spontaneously proliferating lymphocytes from persistently lymphocytotic cows than
      on normal bovine lymphocytes. Antibodies to bovine class I and class II inhibited
      spontaneous lymphocyte proliferation. Results suggest that lymphocyte
      dysregulation in BLV-induced persistent lymphocytosis involves upregulation of
      and signaling through lymphocyte surface molecules which are involved in immune
      activation of lymphocytes.

PMID- 9143378
TI  - The effect of dexamethasone on the expression of activated NF-kappa B in adjuvant
      arthritis.
AB  - The transcription factor NF-kappa B plays a significant role in inflammatory
      diseases. In this study we have investigated the expression of activated NF-kappa
      B p65 subunit in the rat adjuvant arthritis model in a 28-day time-course
      experiment using immunohistochemistry. The expression of p65 was detected in the
      synovial lining layer and around the blood vessels in the inflamed synovium as
      early as Day 3 post-adjuvant injection. The cells that expressed p65 in the
      synovial lining were thought to be macrophage-like synoviocytes. The expression
      was stronger in the injected hindpaw than that in the noninjected hindpaw.
      Dexamethasone treatment at 1 mg/kg p.o. (Days 0-20) suppressed both the hindpaw
      edema and increase in p65 expression. Withdrawal of the treatment caused
      increases in both p65 expression and paw volume. Together these suggest that
      activated NF-kappa B was specifically expressed in the arthritic synovium and may
      play a significant role in the development of arthritis.

PMID- 9143379
TI  - Strong augment effect of IL-12 expression plasmid on the induction of HIV
      specific cytotoxic T lymphocyte activity by a peptide vaccine candidate.
AB  - We previously reported that repeated inoculation of VC1, a macromolecular
      multicomponent peptide vaccine emulsified with Freund's adjuvant (VC1-F), induced
      high cytotoxic T lymphocyte (CTL) levels and a substantial level of multivalent
      antibodies which neutralized various human immunodeficiency virus type 1 (HIV-1)
      isolates. In the present study, we report that inoculation of VC1-F plus
      interleukin (IL)-12 expression plasmid can induce a higher antigen-specific CTL
      response compared to that with VC1-F alone. VC1-F plus IL-12 expression plasmid
      or VC1-F alone were inoculated to BALB/c mice twice at interval of 2 weeks. Two
      weeks after the second inoculation, spleen effector cells from these mice were
      examined. Stronger CTL responses against target cells were observed from the
      inoculation of VC1-F plus IL-12 plasmid than from that with VC-1F alone, but
      there was no difference in antibody induction. The inoculation of VC1 plus IL-12
      plasmid also produced higher CTL activity than the inoculation of VC1 alone.
      These augmented CTL activities were not observed using target cells pulsed with
      non-HIV-specific peptides and different class I haplotype cells. These data
      demonstrate that co-inoculation of cell-mediated immune potent antigen and IL-12
      plasmids can enhance the antigen-specific CTL response. This may be a potential
      approach for the induction of cellular immunization against HIV-1 and other
      diseases.

PMID- 9143380
TI  - Effect of melarsoprol treatment on circulating IL-10 and TNF-alpha levels in
      human African trypanosomiasis.
AB  - The pathogenesis of human African trypanosomiasis (HAT) has been the object of
      considerable research interest but has remained incompletely understood. The
      importance of cytokines in the pathophysiology of this protozoan infection is now
      widely recognized, but the full spectrum of cytokines involved has yet to be
      determined. In the present investigation we compared the plasma concentrations of
      TNF-alpha and IL-10 in normal African controls and patients suffering from
      advanced meningocephalic (late-stage) Trypanosomiasis brucei (T.b.) gambiense
      infections, before and after treatment with the arsenical trypanocide
      melarsoprol. We found that patients with late-stage T. b. gambiense exhibit
      chronically elevated circulating levels of both of these cytokines, and that
      these levels quickly decline following melarsoprol treatment. These findings
      confirm that TNF-alpha is involved in the immunopathogenesis of late-stage
      African trypanosomiasis and suggest that IL-10 may also play an important
      regulatory role in this disease.

PMID- 9143381
TI  - The effects of general anesthesia on human peripheral immune cell distribution
      and cytokine production.
AB  - Anesthetic agents are believed to have an adverse effect on human immune defense
      mechanisms. We investigated changes in peripheral immune cell numbers such as
      natural killer (NK) cells, B cells, and T lymphocyte subpopulations (CD4+ and
      CD8+ cells) and differences in cytokine production after stimulation with
      different mitogens before and during narcosis. We studied 30 patients undergoing
      elective orthopedic surgery. Stimulatory experiments were performed with the
      mitogens lipopolysaccharide, phytohemagglutinin A, and inactivated Newcastle
      disease virus. During general anesthesia with fentanyl, thiopental, and
      isoflurane, there was a significant decrease of circulating NK cells in the
      peripheral blood accompanied by a significant increase of B cells and CD8+ T
      lymphocytes. We detected a significant anesthesia-associated increase of
      interferon (IFN)-gamma, IFN-alpha, tumor necrosis factor-alpha, and soluble
      interleukin-2 receptor (sIL-2R) synthesis after stimulation with different
      mitogens while interleukin (IL)-1 beta and IL-6 protein did not change
      significantly. After the beginning of surgery, CD8-positive cells showed a return
      to control values and NK cell number increased slightly. These findings suggest
      that general anesthesia interferes with immune cell number and immune cell
      response. This may explain the clinically well-recognized disturbance of human
      immunity after surgery and general anesthesia.

PMID- 9143382
TI  - CNS late effects after ALL therapy in childhood. Part I: Neuroradiological
      findings in long-term survivors of childhood ALL--an evaluation of the
      interferences between morphology and neuropsychological performance. The German
      Late Effects Working Group.
AB  - The effect of cranial irradiation on possible therapy-induced morphological
      central nervous system (CNS) side effects of children cured from acute
      lymphoblastic leukemia (ALL) is controversially discussed. In a retrospective
      multicenter study, 118 former ALL patients in first continuous remission were
      investigated using cranial computerised tomography (CCT) or magnetic resonance
      imaging (MRI) scans to evaluate CNS related impairments. Corresponding to the
      different kinds of CNS prophylaxis, the patient sample was divided: group A (n =
      39) receiving intrathecal methotrexate (ITMTX) and systemical medium-high-dose
      methotrexate (SMHDMTX), group B (n = 41) cranial irradiated (in mean 16.8 Gy) and
      administering ITMTX and SMHDMTX, group C (n = 38) irradiated (in mean 17.1 Gy)
      and getting ITMTX. Pathologic scans showed atrophy, leukoencephalopathy,
      calcifications or grey matter changes. These findings were compared with the
      neuropsychological test results. Abnormal MRI or CCI scans were found in 61/118
      patients (51.7%). Fifteen belonged to group A (38.5%), 23 to B (56.1%) and 23 to
      C (60.5%). Patients with definite CNS changes show reduced neuropsychological
      test results. The prevalence of brain alterations seems to appear twice increased
      after lengthening the posttherapeutic interval in irradiated patients as in
      nonirradiated patients. Irradiated patients as an age younger than 2 years at
      diagnosis may show a lower prevalence for developing CNS alterations. CNS
      alterations are not sex-related. Children treated with cranial irradiation in
      combination with SMHDMTX and/or ITMTX were at greater risk of developing
      morphological brain alterations than patients with chemotherapy alone. These
      alterations are partly correlated with reduced neuropsychological performances
      and seem to stay with a longer posttherapeutic interval.

PMID- 9143383
TI  - Long-term survival data and prognostic factors of a complete response to
      chemotherapy in patients with head and neck cancer treated with platinum-based
      induction chemotherapy: a Hellenic Co-operative oncology Group study.
AB  - A group of 154 patients with locally advanced head and neck cancer, treated with
      platinum-based induction chemotherapy, were followed up for 5 years and several
      pretreatment characteristics were analyzed for possible correlation to a complete
      response (CR) to chemotherapy, time to progression (TTP) and overall survival
      (OS). Clinical stage (p = 0.0024) and a history of smoking (p = 0.0125) were
      selected as important prognostic factors for CR by step wise logistic regression.
      We also identified response to chemotherapy (p = 0.0120), age (p = 0.0066),
      clinical stage (p = 0.0363), N stage (p = 0.0028), and tumor grade (p = 0.0101)
      as significant prognostic variables for TTP. Response to chemotherapy (p <
      0.0001) and age (p = 0.0017) were found also significant for OS. These long-term
      prognostic factors which retain their prognostic significance after several years
      of follow-up could be helpful in the design of future trials in this patient
      population.

PMID- 9143384
TI  - The Beckwith-Wiedemann syndrome phenotype and the risk of cancer.
AB  - Beckwith-Wiedemann syndrome (BWS) comprises of a number of childhood
      abnormalities, often associated with one or more tumors. Thirty-eight patients
      were investigated to determine clinical and/or biological signs associated with a
      tumor presence. Our patients exhibited a higher incidence of tumor development
      (21%) than that previously reported, underlying the care with which such patients
      should be followed, when particular clinical features are observed: visceromegaly
      affecting three organs (liver, kidney, spleen), and also family history with sign
      of BWS such as macroglossia, omphalocele, hemihypertrophy, embryonic tumor), high
      body weight at birth (> or = +2 standard deviations and diastasis recti.

PMID- 9143385
TI  - Partial nephrectomy in a cystic partially differentiated nephroblastoma.
AB  - Cystic partially differentiated nephroblastoma (CPDN) is a rare neoplastic
      disorder consisting of a well-demarcated cystic lesion of the kidney where
      blastemal or other embryonic cells are present in the septa of the cysts.
      Magnetic resonance imaging can detect the cystic character of the lesion and will
      produce imaging features that are highly suggestive of either CPDN or cystic
      nephroma (CN) (synonym: multilocular cyst of the kidney), a benign entity.
      Although malignant potential exists in CPDN, all cases reported to date have had
      a favorable prognosis after surgery alone. Partial nephrectomy is considered
      safe, and the treatment of choice in the newborn period. We report a case of CPDN
      in a newborn that was successfully treated with partial nephrectomy. More than
      five years after nephron sparing surgery, the involved kidney shows normal
      anatomical structure except for a diminished upper pole, no evidence of tumor
      recurrence and good renal function.

PMID- 9143386
TI  - Bilaterally multicentric synchronous Wilms' tumor: successful conservative
      treatment despite persistence of nephrogenic rests.
AB  - We report a case of synchronous bilateral Wilms' tumor in a girl with incomplete
      Beck-with-Wiedemann syndrome and hemihypertrophy. Multiple small tumors were
      present in both kidneys. The initial diagnostic biopsy showed stage I monophasic
      blastematous Wilms' tumor of favorable histology, with multiple perilobar
      nephrogenic rests (nephroblastomatosis). By flow cytometry, tumor was diploid,
      with an S-phase fraction of 13.9%. Dactinomycin and vincristine were begun as per
      the National Wilms' Tumor Study IV (18 week course). After 1 month, only a single
      small lesion was evident, which persisted unchanged. Excisional biopsy 5 months
      after beginning chemotherapy showed entirely necrotic tumor but apparently
      unaltered nephrogenic rests. After completing chemotherapy, the child has done
      well, with normal renal function and no evidence of disease 3 years after
      diagnosis. Management of stage V Wilms' tumor is tailored to the individual case,
      being as conservative as possible to spare renal parenchyma. Given the high
      incidence of coexisting nephrogenic rests in bilateral Wilms' tumor, careful
      follow-up is required, as these potentially premalignant rests may resist
      chemotherapy.

PMID- 9143387
TI  - Intra-operative radiation therapy in pediatric neuroblastoma.
AB  - External beam irradiation (EBRT) has been shown to improve response rates and
      event-free survival in children with neuroblastoma and regional lymph node
      metastases. Irradiation during surgical exposure (intra-operative radiotherapy,
      IORT) with displacement of adjacent radiosensitive organs out of the treatment
      field allows for more precise delineation of the target volume and significantly
      reduces the amount of normal tissue exposed to irradiation. We have incorporated
      IORT into the treatment regimen of 24 children with neuroblastoma between the
      years of 1983-1991. IORT was directed to any residual tumor or the tumor bed; the
      median dose of radiation was 1,000 cGY, equivalent to 3,000 cGY of conventional
      EBRT. There were 11 males and 13 females. Two patients had stage II, 12 patients
      had stage III, and 10 patients had stage IV disease. Ten children received IORT
      for suspected recurrent or persistent neuroblastoma. Twelve patients were disease
      free survivors following IORT with a median follow-up of 54 months. For those
      patients with stage III disease, seven children were disease-free survivors,
      while only three of 10 patients with stage IV disease survived (median follow-up
      30 months). Disease-free Survival (DFS) correlated with the achievement of local
      tumor control in children with both stage III and IV neuroblastoma. There was
      limited morbidity and no episodes of obstructive uropathy were encountered. We
      conclude that IORT appears to be well tolerated and may have therapeutic benefit
      for a select group of patients with neuroblastoma. IORT merits future exploration
      by prospective study.

PMID- 9143388
TI  - Lung involvement in neuroblastoma: incidence and characteristics.
AB  - The presence of lung metastases in neuroblastoma often leads to doubt about the
      diagnosis due to rarity of disease at this site. To determine more precisely the
      incidence and nature of pulmonary disease in neuroblastoma the data base of the
      European Neuroblastoma Study Group (ENSG) was examined. Information was obtained
      about 35/746 stage IV patients (and 1 patient who was registered as having stage
      II disease) documented to have pulmonary disease at presentation. Of these 5 were
      registered with pleural effusions, 18 pleural infiltrations, and 13
      intrapulmonary lesions. Review of these cases, however, suggested that only 9
      patients (1.2%; 95% exact confidence interval 0.42-1.99%, binomial distribution)
      had disease consistent with secondary neuroblastoma in lung or pleura. There was
      no correlation with clinical features, age, sex, or other disease sites, and
      outcome was uniformly poor.

PMID- 9143389
TI  - Papillary thyroid carcinoma: demographics, treatment, and outcome in eleven
      pediatric patients treated at a single institution.
AB  - We describe 11 cases (8 females, 3 males) of papillary thyroid carcinoma in
      children treated at St. Jude Children's Research Hospital over a 33-year period,
      and review the literature. Ages ranged from 7-25 years (median, 16 years). Six
      patients had primary papillary thyroid carcinoma. Five patients had secondary
      papillary thyroid carcinoma after treatment of Hodgkin's disease (n = 2), acute
      lymphoblastic leukemia (n = 2), and neuroblastoma (n = 1) with chemotherapy and
      cervical radiation. The typical presentation was either cervical lymphadenopathy
      or a thyroid mass of short duration. Treatment consisted of thyroidectomy,
      cervical lymph node dissection, and postoperative thyroid hormone replacement (n
      = 1), parathyroid reimplantation (n = 1), 131I ablation (n = 4), external-beam
      irradiation (n = 1), and chemotherapy with doxorubicin (n = 1) or carboplatin and
      topotecan (n = 1). Nine patients are alive without evidence of disease 3.0-22.4
      years from diagnosis. One patient has persistent but stable disease 17.3 years
      after diagnosis. One patient relapsed with metastatic lung disease 0.3 years
      after the initial diagnosis. He continues to do well after a brief but
      unsustained complete radiographic remission of disease to combination
      chemotherapy with carboplatin and topotecan. Our review supports excellent long
      term outcome for primary or secondary papillary thyroid carcinoma in pediatric
      patients although complications may require close follow-up in a
      multidisciplinary setting.

PMID- 9143390
TI  - Gastrointestinal smooth muscle tumors and iron deficiency anemia in children.
AB  - Smooth muscle tumors are rarely seen in the pediatric population. We present a
      child with smooth muscle tumor of low malignant potential in the ileocecal valve
      region in whom iron deficiency anemia was the only presenting sign. Abdominal
      computed tomographic (CT) scan, barium enema, and colonoscopy revealed the mass.
      Following resection of the tumor the anemia was corrected and the child feels
      well.

PMID- 9143391
TI  - Phase I trial of subcutaneous interleukin-1 alpha in children with malignant
      solid tumors.
AB  - Interleukin-1 alpha (IL-1 alpha) is myeloprotective in a variety of animal models
      of cancer chemotherapy and is similarly beneficial in adults treated with
      carboplatin, 5-fluorouracil, and after autologous bone marrow transplantation.
      There are no trials of this agent in children. Our purpose was to determine the
      toxicity and maximum tolerated dose (MTD) of recombinant human interleukin-1
      alpha (rhuIL-1 alpha) in children with solid tumors receiving intensive cancer
      chemotherapy and to evaluate its myelo-protective effects. Cohorts of patients
      received rhuIL-1 alpha in doses of 0.1-10 micrograms/m2 for 4 days by
      subcutaneous injection prior to ICF chemotherapy (ifosfamide, 2 g/m2/day x 3,
      carboplatin targeted to an area under the curve of 8 mg/ml x min on day 1, and
      etoposide, 100 mg/m2 daily for 3 days). Patients were randomized to receive rhuIL
      1 alpha before either the first or second course of therapy. After the MTD of
      rhuIL-1 alpha was determined an additional group of patients received rhuIL-1
      alpha at the dose immediately following ICE chemotherapy. The dose-limiting
      toxicities of rhuIL-1 alpha in the 27 children tested comprised systemic symptoms
      of fever, chills, headache, and hypotension. The MTD was 3 micrograms/m2/day.
      There were no differences in chemotherapy-induced hematologic toxicity with
      increasing doses of rhuIL-1 alpha or in comparisons before or after ICE
      chemotherapy. Although rhuIL-1 alpha can be given safely to children receiving
      myelosuppressive chemotherapy, clinical usefulness would mandate a significant
      hematopoietic benefit in view of the trouble some side effects identified. We saw
      no evidence of a hematoprotective effect.

PMID- 9143392
TI  - Validity of the Rotterdam Symptom Checklist in paediatric oncology.
AB  - In order to determine the validity of the Rotterdam Symptom Checklist (RSC) for
      use with paediatric patients, a sample of 47 mothers with a child with acute
      lymphoblastic leukaemia (ALL) was asked to complete the RSC, the Play Performance
      Scale for Children PPSC and a measure of daily activity (HDI: Questionnaires were
      completed during routine outpatient visits. There were no effects of child age on
      number of symptoms reported. The physical symptom subscale of the RSC
      distinguished between children in terms of treatment status and number of
      hospitalisations. However, the psychological symptom subscale did not distinguish
      between these groups. Limitations of the scale for work with children are
      considered. These include difficulties experienced by patents in reporting
      psychological symptoms for their children, and the inappropriateness of a scale
      developed for adults to assess children. In the absence of other measures, the
      RSC can be used for children, but a more developmentally appropriate measures is
      needed.

PMID- 9143394
TI  - Improvement of Langerhans' cell histiocytosis and pancreatitis by alpha
      interferon.

PMID- 9143393
TI  - Arteriovenous fistula: a complication following renal biopsy of suspected
      bilateral Wilms' tumor.

PMID- 9143395
TI  - Successful treatment of orbital rhabdomyosarcoma in two infants using
      chemotherapy alone.

PMID- 9143396
TI  - Angiogenesis as a target for tumor treatment.
AB  - Angiogenesis is a key step in tumor growth, invasion and metastasis. Thus,
      antiangiogenic therapy was postulated to be an attractive approach for antitumor
      treatment. Based on today's knowledge, at least three strategies for inhibition
      of angiogenesis are feasible: (1) inhibition of release of angiogenic factors
      from tumor cells and/or neutralization of angiogenic molecules that have already
      been released: (2) inhibition of vascular endothelial cell proliferation and
      migration, and (3) inhibition of the synthesis and turnover of vessel basement
      membrane. To date, a number of antiangiogenic agents have been identified. In
      animal models, treatment with angiogenesis inhibitors has proven antitumor
      effects. Early clinical experience with angiogenic inhibitors indicates that
      optimal antiangiogenic therapy in the future is likely to be based on the long
      term administration to cancer patients in adjunct to surgery, radiotherapy and
      conventional chemotherapy.

PMID- 9143397
TI  - Haplotypes of human leukocyte antigens among patients with nasopharyngeal cancer
      in Greece.
AB  - The concept that the major histocompatibility complex (MHC) plays an important
      role in the pathogenesis of nasopharyngeal cancer (NPC) in several ethnic groups
      has gained increased attention during the last 15 years. Earlier studies have
      suggested that an increased risk of NPC is associated with specific phenotypes of
      human leukocyte antigens (HLA). The present study was performed to examine the
      association of HLA specificities and haplotypes with NPC in a Greek population.
      In a genotypical study of 53 patients, a significant association between the
      haplotype HLA-B5DR11 and NPC was found, mainly in patients > 45 years. Also, the
      above haplotype was significantly associated with longer disease-free interval.
      HLA-B5 and HLA-B5DR11 were more often seen among patients with squamous cell
      histology than among those with the undifferentiated type. These results suggest
      that MHC loci are probably implicated in the pathogenesis and outcome of NPC in
      Greek patients.

PMID- 9143398
TI  - Angioimmunoblastic lymphadenopathy with dysproteinemia--lack of a prognostic
      value of clear cell morphology.
AB  - It has been suggested that angioimmunoblastic lymphadenopathy with dysproteinemia
      (AILD) is closely related to peripheral T cell lymphoma (PTCL). However, the
      clinical course of AILD-like PTCL is notoriously unpredictable. A minor portion
      of patients enjoyed prolonged remission with steroid-only treatments (indolent
      AILD) while most others died rapidly despite the use of intensive chemotherapy
      (aggressive AILD). Recently, it has been suggested that histological features
      such as the presence or absence of clear cells and convoluted cells are of high
      prognostic value. The validity of this observation was addressed in this study.
      Eighteen patients who presented between 1977 and 1994 at the National Taiwan
      University Hospital were retrospectively studied. There were 11 men and 7 women,
      with a median age of 47 years. Twelve patients had received various regimens of
      systemic chemotherapy, and the other 3 patients had been treated with steroids
      alone. Eight patients had indolent AILD and 6 aggressive AILD. The follow-up
      period in 4 patients was too short to be analyzed. The histopathology of these
      cases was divided, according to the criteria of Aozasa et al., into group I
      (neither cells), 4 patients; group II (only convoluted cells), 1 patient, and
      group III (clear cells with or without convoluted cells), 13 patients. Contrary
      to others, our data revealed that group III patients were doing better than group
      I patients. Univariate analysis of other pertinent clinical features, including
      sex, age, lymphadenopathy, B symptoms, hepatosplenomegaly,
      hypergammaglobulinemia, elevated serum lactate dehydrogenase, and treatment
      regimens, revealed none of them to be prognostically relevant. However, patients
      who had achieved complete remission by steroids or other systemic chemotherapy
      had a significantly better prognosis than those who had not. Together, these
      preliminary data suggested that (1) the presence or absence of clear cells and
      convoluted cells failed to predict the clinical behavior, and (2) induction of
      complete remission by steroids or other chemotherapeutic agents is an important
      prognostic index.

PMID- 9143399
TI  - A phase II study of flutamide in ovarian cancer.
AB  - A phase II study of flutamide was conducted in 24 patients with stage III and IV
      ovarian cancer who failed chemotherapy and who had measurable disease. Flutamide
      was administered at a dose of 100 mg three times daily continuously until
      evidence of progression. Partial response observed in 1 of the 23 evaluable
      patients (4.3%) lasted 3 months. Two patients had stable disease (8.7%) for 7 and
      8 months. The remaining 20 patients had progression of disease within 3 months.
      Toxicity was mild.

PMID- 9143400
TI  - A phase II study of carboplatin in nasopharyngeal carcinoma.
AB  - This is a phase II study to evaluate the efficacy and toxicity of short-course
      carboplatin in advanced-stage nasopharyngeal carcinoma (NPC). Thirty-three
      previously untreated stage III-IV NPC patients were studied. Carboplatin was
      given as a rapid intravenous injection every 3 weeks. The dose of carboplatin was
      calculated according to the individual patient's creatinine clearance and desired
      platelet nadir of 75,000/microliter according to the Egorin formula. Response and
      toxicity were evaluated. Thirty-two patients were evaluated for response. The
      median age was 54 years, range 30-70 years. Twenty-four patients had local
      regional disease and 8 patients had metastatic disease. The median dose of
      carboplatin given was 415 mg/m2 (range 91-791 mg/m2). Fourteen (44%) patients had
      a partial response with a 95% confidence interval of 26-62%. Fifteen (47%)
      patients had stable disease and 3 (9%) progressive disease. The overall median
      survival rate was not reached at 43 months. Overall toxicity was tolerable. Grade
      III-IV myelosuppression occurred in 4 (12%) patients. There were no other major
      toxicity- or treatment-related deaths. We conclude that carboplatin has a
      significant anticancer effect in advanced NPC. Thus carboplatin combination
      chemotherapy for the treatment of NPC is worthy of future clinical
      investigations.

PMID- 9143401
TI  - Intra-operative radiotherapy--5 years of experience in the palliative treatment
      of recurrent and advanced head and neck cancers.
AB  - Recurrent and advanced cancer in the head and neck region is usually associated
      with limited therapeutic concepts and a dismal prognosis. Efforts mainly focus on
      palliative treatment in order to improve the patient's quality of life. From May
      1989 to December 1994, a total of 120 intra-operative radiotherapy (IORT)
      procedures with high-energy electron beams (mean energy: 7 MeV: mean dose: 20 Gy)
      were performed in 95 patients. Therapy was usually performed under endotracheal
      anaesthesia (84%). There were 91 cases (75.8%) of recurrence in the lymph nodes
      of the neck and 14 cases (11.7%) of local recurrence. 15 patients (12.5%)
      received IORT as part of the initial treatment. Considering the palliative nature
      of IORT in these patients, only an R2 resection (gross residual tumour) was
      achieved in 71.7%. Local tumour control was nonetheless possible in 17% (R2
      resection) to 64% (complete R0 resection), with a mean 11-month follow-up period
      for survivors (mean for deceased patients: 8 months). Regarding palliative
      criteria, IORT proved to be feasible since patients profited from short
      hospitalisation (median: 10 days), a low complication rate (27 instances; e.g.
      tracheostomy: 11; necrosis: 8, or fistula: 3) and, in part, a substantial
      reduction of pain (73.8%). Most of them regained physical and psychic integrity
      for weeks to months and were able to take part in social life during the final
      stage of their disease.

PMID- 9143402
TI  - Lack of loss of heterozygosity at the c-erbA beta locus in gastrointestinal
      tumors.
AB  - The cellular homologues of the viral oncogene c-erbA encode for the nuclear
      thyroid hormone receptor c-erbA (TR). The gene for the human TR beta subtype is
      located on chromosome 3p24, and a loss of heterozygosity around this region has
      been reported in breast and small cell lung cancers, suggesting that TR beta
      might act as a tumor suppressor gene. In the present study, we used PCR-based
      restriction fragment length polymorphisms to examine the 3p24 region of 19
      patients with gastrointestinal tumors for loss of heterozygosity (LOH).
      Interestingly, only 1 of the patients had an LOH at this locus, while 4 patients
      had a microdeletion of both alleles in the 3p24 region. These results suggest
      that, in contrast to previous reports on lung and breast cancers, a loss of
      heterozygosity of the TR locus at 3p24 is a rare event. A critical review of the
      literature, however, suggests, that some of the earlier studies have used markers
      whose location is only imprecisely mapped and may hence point to a tumor
      suppressor gene candidate other than TR beta. However, a selective microdeletion
      of both alleles was detected in the tumors of 4 of the 19 patients, indicating
      that this region on chromosome 3p may be genetically unstable in gastrointestinal
      tumors.

PMID- 9143403
TI  - Studies of the expression of epidermal growth factor receptor in human renal cell
      carcinoma: a comparison of immunohistochemical method versus ligand binding
      assay.
AB  - We evaluated the expression of epidermal growth factor receptor (EGFR) in 21
      patients with renal cell carcinoma (RCC) by immunohistochemical staining of
      frozen tumor sections using a monoclonal antibody for EGFR and by a ligand
      binding method using radiolabeled epidermal growth factor. EGFR was detected in
      16 of the 21 cases by ligand binding, while 11 of the 21 cases were detected by
      immunohistochemical staining. A significant correlation was observed between the
      two methods in detecting EGFR (p < 0.0001). EGFR was detected by the ligand
      binding method in all patients who died of RCC. Four cases that were graded as
      EGFR-negative on immunohistochemistry died of RCC. Observations suggest the
      ligand binding method was more sensitive than the immunohistochemical method in
      detecting EGFR and forecasting patient survival.

PMID- 9143404
TI  - Soluble CD44 variants in the serum of patients with urological malignancies.
AB  - In patients with malignant diseases, characteristic alterations in the expression
      of CD44 protein and their variants were found. For the present study, the serum
      concentrations of the standard isoform CD44 std and the two variant isoforms CD44
      v5 amd CD44 v6 were measured by ELISA in patients with prostate cancer (n = 49),
      benign prostatic hyperplasia (n = 30), renal cell carcinoma (n = 31) and bladder
      cancer (n = 29). The data were compared with the results of 30 healthy men and 30
      healthy women. The sCD44 v5 concentrations in patients with prostate cancer (p <
      0.01), benign prostatic hyperplasia (p < 0.01) and men with renal cell cancer (p
      < 0.01) were significantly lower than those measured in the male control group.
      The sCD44 v5 concentrations observed in male patients with bladder cancer were
      lower than in the male control group (p < 0.05). Only in one group the
      concentration of sCD44 std differed significantly from the others. The sCD44 std
      concentration in male patients with renal cell cancer was significantly lower
      than in the male control group (p < 0.01). Other significant differences were not
      found. In contrast to results observed in other carcinomas, the determination of
      soluble CD44 proteins in serum cannot be recommended as a marker for urological
      malignancies.

PMID- 9143405
TI  - Inverse relationship between P-glycoprotein expression and its proliferative
      activity in hepatocellular carcinoma.
AB  - Hepatocellular carcinomas (HCCs) from 31 patients, cirrhotic livers from 7
      patients and normal liver from 8 patients were immunohistochemically assessed in
      frozen sections using anti-P-glycoprotein (Pgp) monoclonal antibody C219.
      Immunohistochemical staining with anti-Ki-67 monoclonal antibody MIB-1 was
      performed for 22 HCCs to assess proliferative activity. Tumor tissues expressed
      Pgp on the biliary surface and on the luminal surface of cancer cells, which was
      less extensive than in normal and cirrhotic liver hepatocytes. Expression of Pgp
      was closely associated with the degree of histological differentiation and the
      histological type of HCC. Labeling indices (LI) of Pgp expression were 0.68 +/-
      0.06 (mean +/- SD) in well, 0.51 +/- 0.14 in moderately and 0.04 +/- 0.06 in
      poorly differentiated HCC (significant differences among the three groups). LI of
      Pgp expression in the trabecular (0.55 +/- 0.15) and in the pseudoglandular types
      (0.44 +/- 0.10) were remarkably higher than in the compact type (0.04 +/- 0.06).
      The extent of Pgp expression in HCC was significantly inversely related to the
      extent of Ki-67 expression, in which Pgp expression decreased in highly
      proliferating tumors. In conclusion, Pgp expression in HCC was clearly related to
      its proliferative activity.

PMID- 9143406
TI  - Immunohistochemical detection of bcl-2 and p53 proteins and apoptosis in soft
      tissue sarcoma: their correlations with prognosis.
AB  - Information on prognostic factors is essential to establish appropriate
      therapeutic modalities for soft tissue sarcoma (STS). To evaluate the biological
      nature and prognostic factors of STS, p53 and bcl-2 expression was
      immunohistochemically studied on paraffin-embedded sections from 70 patients with
      STS in the extremities and trunk. In addition, the degree of apoptosis was
      examined by in situ end-labeling. Histologic diagnoses in these cases were
      malignant fibrous histiocytoma in 29 cases, liposarcoma in 11, synovial sarcoma
      in 11, leiomyosarcoma in 5, malignant neurogenic tumor in 5, and others in 9.
      Tumor cells in 31 of 70 cases (44%) showed positive nuclear staining for p53
      protein. There was no correlation between p53 expression and tumor size,
      histologic grade, argyrophilic nucleolar organizer region (AgNOR) count,
      cellularity and extent of neerosis. Expression of p53 did not correlate with
      survival of patients. Tumor cells in 24 of 56 cases (43%) were positive for bcl-2
      protein expression. The frequency of bcl-2 expression in the tumor cells showed a
      direct proportion to tumor size (> or = 10 vs. < 10 cm) but inverse proportion to
      AgNOR counts and cellularity. The 5-year survival rate in patients with bcl-2
      positive tumors (87%) was more favorable than in those with bcl-2-negative tumors
      (53%; p < 0.05). The frequency of apoptosis in low-grade STS was significantly
      higher than that in the intermediate and high-grade STS (p < 0.001). Extent of
      necrosis, a well-known prognostic indicator in STS, was not correlated with the
      frequency of apoptosis. Multivariate analysis showed that cellularity, bcl-2 and
      AgNOR counts were independent prognostic factors in patients with STS. The
      current study revealed that STS with a higher expression of bcl-2 had lower
      proliferative activity and larger size than those without. Immunohistochemical
      detection of bcl-2 is useful for predicting prognosis in patients with STS.

PMID- 9143407
TI  - Growth kinetic study of human hepatocellular carcinoma using proliferating cell
      nuclear antigen and Lewis Y antigen: their correlation with transforming growth
      factor-alpha and beta 1.
AB  - The factors which control the balance between proliferation and cell death in
      hepatocellular carcinoma (HCC) remain unclear. The kinetic state of the tumor
      growth was investigated in the present study with references to transforming
      growth factor (TGF)-alpha and -beta 1 in 50 resected HCCs without preceding
      therapies. three-micrometer sections were cut from formalin-fixed, paraffin
      embedded tumors. Proliferating cell nuclear antigen (PCNA), Lewis Y antigen
      (LeY). TGF-alpha, and -beta 1 were immunohistochemically stained and
      quantitatively assessed with an image analyzer. By means of immunohistochemical
      staining, a reciprocal correlation was observed between PCNA and LeY. A similar
      pattern was found between TGF-alpha and -beta 1, although not so strikingly as in
      the case of PCNA and LeY. The expression of LeY and PCNA labeling index (LI)
      ranged from 0 to 56.1% and from 0 to 52.8%, respectively. A correlation was
      observed between LeY and tumor size (r = 0.302, p < 0.04), while there was no
      significant relationship between PCNA LI and tumor size (r = -0.048, p > 0.05).
      The positive area ranged from 0 to 61.6% for TGF-alpha, and from 0.6 to 71.5% for
      TGF-beta 1. Analysis of these data showed a significant correlation between TGF
      beta 1 and tumor size (r = -0.327, p < 0.03). Among HCCs < 5 cm, PCNA LI
      positively correlated with tumor size (r = 0.399, p < 0.04), but negatively with
      TGF-beta 1 (r = -0.431, p < 0.03). In conclusion, the present investigation
      indicates that the simultaneous analyses of proliferating and apoptotic
      activities by means of PCNA and LeY could yield more accurate data to determine
      the kinetic state of the tumor growth compared with either alone. In addition,
      TGF-beta 1 might act as a suppressive factor in the growth of HCC < 5 cm.

PMID- 9143408
TI  - Mutational state of von Hippel-Lindau and adenomatous polyposis coli genes in
      renal tumors.
AB  - Genetic alterations of the von Hippel-Lindau (VHL) tumor suppressor gene and the
      adenomatous polyposis coli (APC) gene in renal tumors were examined by PCR-SSCP
      analysis and direct sequencing. Tissues from 58 primary sporadic human renal cell
      tumors (49 clear-cell carcinomas, 6 non-clear-cell carcinomas and 3 oncocytomas)
      from Japanese patients were used in this study. Somatic VHL mutations were
      detected in 26 (53%) of the clear-cell carcinomas, although no mutations in this
      gene were observed in any non-clear-cell carcinomas or oncocytomas. The frequency
      of mutations did not correlate with histological grade, clinical stage or any of
      several other clinical factors examined. No differences in the frequency of VHL
      mutations or in the exons where mutations occurred within the gene were evident
      when we compared our results with those reported for American patients. However,
      frameshifts were more common in our Japanese panel of tumors than in American
      cases, where single-point mutations appear to be more frequent. No APC gene
      mutation was detected in any of our samples. These results indicate that VHL gene
      mutations are related to the carcinogenesis of the clear-cell type of primary
      renal cell carcinomas, whereas alteration of the APC gene is not involved in the
      pathogenesis of this cancer.

PMID- 9143409
TI  - Ultrastructural criteria that prove the similarities between amphibian and human
      tumors.
AB  - Toads fed with 0.5 mg 7,12-dimethylbenz(a)anthracene twice a week for 12 weeks
      displayed liver tumors in 27 out of 100 cases. Electron micrographs of liver
      tumors showed some criteria of malignancy, such as the presence of nuclear
      pockets, pseudoinclusions, dilatation of the cisternae of rough endoplasmic
      reticulum and loss of cell junctions. These features are closely similar to those
      of true malignancy described in humans and other mammals.

PMID- 9143410
TI  - Interactions of lymphokine-activated killer cells and A549 lung carcinoma nodules
      maintained in three-dimensional culture.
AB  - Lymphokine-activated killer (LAK) cells were cocultured in the presence of
      interleukin-2 (IL-2), with pulmonary surfactant secreting A549 lung carcinoma
      nodules and maintained in continuous three-dimensional culture for 2-6 days in an
      attempt to test the response of tumor cells which produce LAK cell inhibitory
      substances. The A549 nodules secrete mucus which envelops them. This mucus is
      also secreted inside pseudoalveolar structures characteristic of these nodules.
      The mucus contains the pulmonary surfactant and sialomucins, both LAK cell
      inhibitory substances. The spontaneous infiltration into the neoplastic tissue
      and the membrane contacts established between the two cell types were studied by
      means of histological, immunohistochemical and electron-microscopic methods. Free
      floating LAK cells were allowed to sediment and adhere freely to the nodule
      surface. The cytostatic and cytolytic effects of LAK cells were tested using
      thymidine incorporation into DNA and flow cytometry. Despite the presence of a
      mucus envelope, LAK cells adhered to the A549 nodule surface and penetrated
      spontaneously into them in the presence of IL-2; they settled mainly in the
      pseudoalveolar structures where they became apoptotic. According to electron
      microscopic observations performed on the second day of coculture, the LAK cells,
      which remained between the cancer cells, established mostly pinpoint contacts
      with the carcinoma cells, forming cytoplasmic fusions. These fusions indicate the
      induction of pores in both the cancer cell and the LAK cell membranes. Electron
      microscopic observation also displayed LAK-cell-associated apoptotic and necrotic
      carcinoma cells. However, at this stage of the coculture (day 2), the DNA
      synthesis rate of the A549 nodules still remained unchanged; it diminished by
      approximately 3 times on day 4 and almost stopped on day 6: nodule disintegration
      was then complete. In the free-floating LAK cell component of the cocultures, DNA
      synthesis was already strongly inhibited (26x) by the second day. Nevertheless,
      their cytolytic effect remained unaltered, as was tested on A549 monolayer cells.
      The presence of tumor necrosis factor (TNF) in the coculture supernatant has been
      demonstrated, and when coculturing took place in the presence of monoclonal TNF
      antibody, nodule proliferation was significantly enhanced (up to 145%). Our
      results indicate that, despite the presence of pulmonary surfactant and
      sialomucins containing mucus, LAK cells were capable of killing lung carcinoma
      cells in three-dimensional culture at an early stage of coculture (day 2) by
      direct cell-to-cell contact. Total nodule disintegration, however, was complete
      much later (on day 6), and taking into account the low amount of LAK cells in the
      cancer tissue, this seemed to be the result of an indirect effect implying, in
      particular, the presence of soluble TNF.

PMID- 9143411
TI  - Pathological and genetic correlates of apoptosis in the progression of colorectal
      neoplasia.
AB  - PURPOSE: Apoptosis is commonly observed in a variety of human tumors, and some of
      the genetic events which control this process have been identified in vitro. The
      aim of this study was to determine the frequency of apoptosis in colorectal
      neoplasms and to examine its relationship to a number of pathological parameters,
      to the presence of mutations in the p53 tumor suppressor gene, and to
      overexpression of the bcl-2 oncoprotein. METHODS: A total of 109 colorectal
      neoplasms (26 adenomas 83 carcinomas) were examined. An in situ end-labelling
      assay was used to detect apoptosis in paraffin-embedded tumor sections, and
      scores were determined by light microscopy. The p53 and bcl-2 status were
      determined by immunohistochemistry. RESULTS: Apoptotic frequency increased with
      tumor progression. Normal mucosa contained significantly fewer apoptotic cells
      than adenomas or carcinomas. Similarly adenomas showed less apoptosis than
      carcinomas, and the frequency of apoptosis increased with Dukes' stage. Overall,
      changes in apoptotic frequency were inversely related to the level of bcl-2
      expression, but were not related to the p53 status of the tumors. CONCLUSIONS:
      The frequency of apoptosis in colorectal neoplasia appears to increase in the
      course of tumor progression in association with a decline in bcl-2 expression,
      but is not influenced by p53 gene mutations.

PMID- 9143412
TI  - Microsatellite instability and loss of heterozygosity in primary breast tumours.
AB  - Allelic imbalance or loss of heterozygosity (LOH) studies have been used
      extensively to identify regions on chromosomes that may contain putative tumour
      suppressor genes. We looked for evidence of microsatellite instability (MI) and
      LOH on chromosome 7q, 10q, 11p and 17q using seven polymorphic microsatellite
      markers. In 42 paired breast cancer-peripheral blood DNA samples we identified 24
      tumours (57%) exhibiting genetic alterations. Twenty-one specimens exhibited LOH
      (50%), while 11 specimens exhibited MI (26%) in at least one microsatellite
      marker. The most frequent incidence of LOH was found for the marker THRA1 (8/33,
      24%) indicating that thra I gene becomes a strong candidate tumour suppressor
      gene, whereas of MI it was D10S109 (3/26, 12%). These MI and LOH data were
      analysed using a range of clinicopathological parameters. Tumours displaying MI
      with no evidence of LOH and tumours exhibiting MI and LOH belonging to stage II
      or III were found, however none were at stage I. These data suggest that MI may
      be an early event in mammary tumorigenesis whereas LOH occurs at a late stage. A
      significant association between the absence of oestrogen receptors (p < 0.01) and
      the absence of both oestrogen and progesterone receptors (p < 0.001) at 17q21
      were observed, indicating a possible relationship between specific genetic
      changes at this region and hormonal deregulation in the progression of breast
      cancer.

PMID- 9143413
TI  - Discordance in p53 mutations when comparing ascites and solid tumors from
      patients with serous ovarian cancer.
AB  - We performed a mutational analysis of the p53 gene in matched samples of solid
      tumors and ascites from patients with ovarian cancer using the single-strand
      conformation polymorphism technique on exons 5-9 of the p53 gene on fresh and
      cultured material. We observed a discordance in the pattern of p53 mutations
      between the ascites and their solid tumor counterpart. In two cases, cancer cells
      from ascites carried a p53 mutation and the corresponding solid tumor cells
      retained the wild-type allele, while the opposite pattern was observed in two
      other patients samples. These results suggest that ovarian tumor cells within the
      ascites may not simply represent cells shed from the ovarian solid tumor and bear
      directly on gene therapy strategies in ovarian cancer.

PMID- 9143414
TI  - Comparison of sialyl-Lewis a-carrying CD43 and MUC1 mucins secreted from a colon
      carcinoma cell line for E-selectin binding and inhibition of leukocyte adhesion.
AB  - The colon carcinoma cell line COLO 205 has earlier been shown to express and
      secrete two mucin-type glycoproteins, the leukocyte-associated sialoglycoprotein
      CD43 or leukosialin (named L-CanAg) and the MUC1 mucin (named H-CanAg). Both
      glycoproteins carry sialyl-Lewis a epitopes and could bind transfected COS cells
      expressing E-selectin in a Ca(2+)- and E-selectin-dependent way. Using the
      monoclonal antibodies C50, C241 (both against sialyl-Lewis a), and CSLEX1
      (against sialyl-Lewis x), the MUC1 mucin was shown to express both sialyl-Lewis a
      and sialyl-Lewis x epitopes, while the CD43 mucin expressed sialyl-Lewis a and
      almost no sialyl-Lewis x epitopes. These two secreted glycoproteins could inhibit
      human polymorphonuclear leukocyte or HL-60 cell adhesion to E-selectin
      transfected COS cells or IL-1 beta-stimulated human endothelial cells in vitro.
      The inhibitory efficiency of the MUC1 mucin was 5-10 times larger than that of
      the CD43 mucin, when studied on endothelial cells and comparable amounts of
      sample were used. Removing the sialic acids from the MUC1 or CD43 mucins by
      sialidase treatment abolished the inhibitory effect. Monoclonal antibodies
      against sialyl-Lewis a greatly and equally inhibited the binding of the MUC1 or
      CD43 mucins, whereas an antibody against sialyl-Lewis x (CSLEX1) showed almost no
      inhibitory effect. The result proposes that the sialyl-Lewis a epitope on at
      least some mucin-type molecules bind E-selectin better than sialyl-Lewis x and
      that the potency of tumor-secreted mucins to interfere with leukocyte attachment
      to E-selectin could be dependent on the apoprotein size or its presentation of
      the carbohydrate epitopes.

PMID- 9143415
TI  - Serum levels of C-erbB-2 (HER-2/neu) in patients with malignant and non-malignant
      diseases.
AB  - The diagnostic value of a new tumor marker, c-erbB-2, was studied in the sera of
      50 controls, 112 patients with benign diseases and 534 patients with
      malignancies. Using 15 U/ml as the cutoff, no healthy subjects, patients with
      benign diseases (excluding liver cirrhosis) or patients with no evidence of
      disease (45 patients) had serum levels higher than this limit. Abnormal c-erbB-2
      levels were found in 38.5% (10 of 26) of the patients with liver cirrhosis and in
      26.7% (8 of 30) of those patients with primary liver cancer. No differences were
      found between the c-erbB-2 serum concentrations in liver cirrhosis or primary
      liver cancer, suggesting the possible catabolism of this antigen in the liver.
      Abnormal levels of this antigen were found in 20% (56 of 278) of the patients
      with breast carcinoma (locoregional 7%, metastases 41.5%), in 21% (6 of 28) of
      ovarian carcinomas (stage I-II 0%, stage III-IV 42.8%), in 21% (3 of 14) of the
      colorectal tumors (locoregional 0%, metastases 30%), and in 13.3% (11 of 83) of
      the patients with lung cancer (locoregional 11.5%, metastases 16%). C-erbB-2
      sensitivity in other patients with advanced disease was: 25% (9 of 36) in
      prostatic cancer, 22% (2 of 9) in gastric cancer, and 11% (1 of 9) in vesical
      tumors. When patients with liver metastases were excluded abnormal c-erbB-2 serum
      levels were only found in breast, lung, prostatic and ovarian carcinomas. C-erbB
      2 sensitivity in patients with lung cancer was related to tumor histology with
      significantly higher value in non-small cell lung cancer (mainly adenocarcinomas)
      than in patients with small cell lung cancer (p < 0.013). C-erbB-2 concentrations
      in patients with breast cancer were significantly higher in patients with
      recurrence (mainly bone and liver metastases) and in patients with progesterone
      receptor-negative (< 15 fmol/mg) tumors (p < 0.01). In conclusion, c-erbB-2 is
      not a specific tumor marker and abnormal serum levels may be found in patients
      with liver pathologies. Its sensitivity suggests its possible application as a
      tumor marker in breast, ovarian, lung (mainly adenocarcinomas) and prostatic
      tumors.

PMID- 9143417
TI  - Endermologie (LPG): does it work?

PMID- 9143416
TI  - Noninvasive mechanical body contouring: a preliminary clinical outcome study.
AB  - L.P.G.'s Endermologie is a massage method consisting of positive pressure
      rolling, in conjunction with applied negative pressure to both the, skin and
      subcutaneous tissues (L.P.G. Endermologie U.S.A., 3101 North Federal Highway,
      Suite 301 Fort Lauderdale, Florida 33306, U.S.A., (800) 222-3911). Devised in
      France during the 1970s, L.P.G.'s original purpose was to soften scars and
      standardize physical therapy; however, patients treated with the L.P.G. machine
      also showed an improvement in body contour and skin texture. Since then, several
      thousand machines have been in use in France as an alternative method for
      altering fat distribution in the subcutaneous plane. The authors began a study to
      determine the safety and efficacy of this machine. This study is composed of 22
      women between the ages of 24 and 48. All 22 women completed at least seven
      sessions of treatments. Six of these 22 women completed all 14 sessions of the
      prescribed treatments. The study group exhibited a wide range of body habitus,
      initial weights, and final results. Of the 22 women who completed seven sessions
      of treatment, three had an increase in body weight and a mean index (see
      Materials and Methods) reduction in body diameter of 1.38 cm (0.5 in). Three of
      the six patients who completed all 14 treatment sessions had an increase in body
      weight and a mean index reduction in body diameter of 2.85 cm (1.12 in). All but
      one of the patients had a decrease in their mean body diameter index, regardless
      of their loss or gain in weight.

PMID- 9143418
TI  - Anatomical study on the temporal fascial layers and their relationships with the
      facial nerve.
AB  - The recent application of endoscopic techniques in facial rejuvenation has
      stimulated a new interest in the anatomy of this region. In endoscopic face lift,
      as in open techniques, one of the main steps is the conjunction of dissections of
      the upper and midface without damage to the frontal branch of the facial nerve.
      This article provides an accurate account of the organization of the temporal
      fascial layers and their relationship with the facial nerve. The authors'
      dissections confirm that the frontal branch, despite the variations in branching
      patterns, has an anatomical relationship with the surrounding fasciae that can be
      deemed constant and predictable: The frontal branch lies in the deep layer of the
      fatty tissue interposed between the suprazygomatic extension of the superficial
      musculoaponeurotic system (SMAS) and the superficial leaflet of the temporal
      aponeurosis. The arrangement of the temporal fasciae on the zygomatic arch is
      also discussed.

PMID- 9143419
TI  - Anatomical variations analysis of the external jugular vein, great auricular
      nerve, and posterosuperior border of the platysma muscle.
AB  - This article describes the observations collected from the dissection of 10
      nonformalinized cadavers analyzed in respect to the anatomical relation
      variations between the external jugular vein, the great auricular nerve, and the
      posterosuperior border of the platysma muscle.

PMID- 9143420
TI  - Cephalometric analysis and postoperative results in aesthetic rhinoplasty.
AB  - The current tendency to perform corrective rhinoplasty with the help of
      computerized images or cephalometric evaluations is justified by the need to
      adapt the amount of correction to all of the cephalometric relationships and draw
      on indications on the exact quantity of tissue to add or remove. We propose a
      very simple standard of surgical planning, which permits obtaining immediate data
      on the position of the jaw, the maxilla, and the correct nose proportion, and we
      confront the results of surgical planning with the postoperative.

PMID- 9143421
TI  - Evaluation of the median forehead flap and the nasolabial flap in nasal
      reconstruction.
AB  - Basal cell carcinoma, which accounts for 70%-80% of all cutaneous malignancies in
      the United States, has increased recently in Japan. We compared methods for
      reconstruction after surgery for basal cell carcinoma, which is expected to
      increase further in the future. Thus patients who underwent reconstruction after
      surgery for basal cell carcinoma of the nose using medial forehead flaps and
      nasolabial flaps were selected, and the effectiveness of these flaps was compared
      by taking the size and location of the tissue defect into consideration. As a
      result, possibly because of anatomical and histological differences of the face
      between Caucasians and Asians, better results were obtained with nasolabial flaps
      than with median forehead flaps.

PMID- 9143422
TI  - Donor site morbidity post-conchal cartilage grafting.
AB  - Morbidity of the conchal cartilage donor site is evaluated in this article. Forty
      two patients (from 1984-1994) with 44 donor sites were reviewed retrospectively.
      In 27 cases an anterior approach was used and in 17 cases a posterior approach
      was used. Four complications were observed: two cases of delayed healing in the
      post auricular approach, one case of flattening of the ear after an anterior
      approach, and one case with an anterior hypertrophic scar was seen. Only one case
      needed further surgical intervention. The anterior approach is technically easy,
      safe, and quick to perform but should be avoided in patients with a history or
      genetic predisposition to keloid or hypertrophic scars.

PMID- 9143423
TI  - Textured surface silicone breast implants: histology in the human.
AB  - Previous studies on the interaction of textured silicone breast implants has
      analyzed tissue expanders or used animal models. To date, the data on long-term
      results of the textured silicone breast implants have not examined permanent
      implants or in vivo effects in the human. A prospective study was designed to
      examine the interaction of textured silicone breast implants in a human over
      several years. A single surgeon, standard surgical technique, and single-type
      implant design were included. The results revealed 78% had silicone particles in
      the tissue immediately adjacent to the implant interface. No distant migration,
      metaplasia, or adverse effects were noted. Our results indicate that silicone
      fragmentation is common but appears to be confined to the local environment.

PMID- 9143424
TI  - Evolution of the vertical reduction mammaplasty: the S approach.
AB  - The vertical reduction mammaplasty has been popularized over recent years. It
      always produces marked puckering of the excess skin and requires revision surgery
      for the persistent dog-ears that develop. Minor complications are often common.
      As a result, the evolution with S approach is developed. A series of 36
      consecutive patients who underwent the S approach reduction mammaplasty is
      presented. The S approach can be described as having 1) superior dermoglandular
      pedicle, 2) simple and safe S-shaped skin marking, 3) suspension of the residual
      glandular tissues transversely to the periosteum of the 5th rib, and 4) short
      scar closure. The surgical techniques are described in a step-by-step fashion. An
      analysis is made of the results obtained from these patients. The mean follow-up
      period of this study is 21 months. As a result of surgical operation, the
      symptoms of breast hypertrophy were markedly improved. According to patient
      assessment, neck, back, or chest pain decreased from 64% to 25%, shoulder
      grooving improved from 56% to 25%, stooped posture decreased from 42% to 14%,
      intetrigo improved from 36% to 8%, psychological embarrassment decreased from 33%
      to 8%. The postoperative complications included minimal areolar epidermolysis
      (11%), hypertrophic scar (8%), etc. All mammograms revealed hypertrophic patterns
      of the breast. The glandular tissues removed had a mean of 480 g from each
      breast. Two breasts (3%) had fibroadenomas. The sternal notch-nipple distance
      changed from a mean of 30.5 cm preoperatively to 20.5 cm, the length of
      infraareolar scar was 9 cm in average. Eighty-one percent of patients had minimal
      postoperative ptosis, and the sensitivity of nipple-areola complex was unchanged
      in 75% of patients. Nine patients (24%) retained the ability to lactate for more
      than 1 month postoperatively. Twenty-two patients (61%) were very satisfied with
      their operation, and eight (22%) were adequately satisfied. The technique
      presented is a simple and safe procedure that provides satisfactory results for
      patients with breast hypertrophy.

PMID- 9143425
TI  - Breast implantation and the incidence of upper extremity somatic complaints.
AB  - Attention has been drawn to elevated laboratory tests of inflammation as
      indicators of a possible reaction to silicone breast implants. These patients
      have complaints of joint pain, pain, and myalgia that were possibly caused by a
      reaction to silicone. This study is a retrospective review of 100 consecutive
      patients (79 female, 21 male) who were evaluated because of a purported
      industrial injury to the upper extremity. Patients were examined by a single
      examiner and all had laboratory screening for indicators of inflammation
      (sedimentation rate, anti-nuclear antibody levels, C-reactive protein, anti
      streptolysin, rheumatic factor), endocrine abnormalities (thyroid panel), and
      serum glucose. None of the patients had any history of breast augmentation with
      any implant. Of the 79 female patients, 50 had an identifiable clinical diagnosis
      and 18 of them had elevation of at least one of the indicators of inflammation.
      The remaining 29 did not have an identifiable diagnosis and 21 of them had
      elevation of at least one indicator of inflammation (P < 0.01). There were 74 out
      of 79 females with subjective complaints of upper extremity pain, joint pain, and
      aching. Forty-five of these patients had an identifiable diagnosis and 17 of them
      had elevation of at least one inflammatory indicator. Of the 74 female patients,
      29 had no identifiable diagnosis and 21 of them had elevation of at least one
      inflammatory indicator (P < 0.01). In summary, there were a high number of female
      patients with complaints of upper extremity symptoms with no prior exposure to
      silicone from breast implantation. There was a statistically significant
      correlation in these patients who had no identifiable diagnosis and elevated
      indicators in inflammation. This study suggests these markers of inflammation
      should not be used as indicators of a reaction to silicone from breast
      implantation in patients with upper extremity subjective complaints.

PMID- 9143427
TI  - Skin resurfacing with laser in Asians.
AB  - The carbon dioxide laser has been a popular dermatological tool, but for the
      cosmetic surgeon. The laser's usefulness has been limited due to the risk
      associated with hyperpigmentation and scarring, when attempting superficial
      aesthetic surgery. The new Tru-Pulse CO2 Laser (Tissue Technology, Inc.)
      overcomes this limitation by providing a unique pulse duration of 60 microseconds
      designed to reduce thermal damage and designed to promote rapid healing. Laser
      resurfacing with the Tru-Pulse Laser provides many potential benefits.

PMID- 9143426
TI  - Inflammatory reaction and capsular contracture around smooth silicone implants.
AB  - Histologic studies were performed on capsular tissue resected from 21 patients
      who were implanted with smooth silicone prostheses filled with gel. The results
      disclosed a nonuniform response to the implants. The granulomatous reaction to
      the silicone showed important variations along the same surface of the implants,
      between the plane and the concave surfaces, between equivalent points at the
      right and left sides, and among the patients. Also, a significant difference was
      observed between reactions and capsules in early and late stages. The author
      believes these variations of the capsular inflammatory reaction promote different
      sites of contraction between cell-to-cell, or cell-to-collagen-to-cell. These
      adding forces result in vectors of different intensities and directions around
      the implants which explains the various clinical grades of capsular contracture.

PMID- 9143428
TI  - Treatment of nevus of Ota by Q-switched ruby laser.
AB  - The effectiveness of the Q-switched ruby laser was investigated in 38 patients
      with nevus of Ota at more than 10 months after the first irradiation. In 14
      patients who were followed-up for a mean of 25.2 months after the first
      treatment, the effectiveness was evaluated as "excellent" in eight patients
      (57%), "good" in four patients (28%), and "fair" in two patients (14%). The mean
      number of irradiation treatments was 7.3 in the "excellent" group, 4.2 in the
      "good" group, and 3.0 in the "fair" group. In 24 patients who were followed-up
      for a mean of 13.6 months after the first treatment, the effectiveness was
      evaluated as "excellent" in eight patients (33%), "good" in 12 patients (50%),
      and "fair" in four patients (16%). The mean number of irradiation treatment was
      5.7 in the "excellent" group, 5.2 in the "good" group, and 2.5 in the "fair"
      group. Even after repetitive irradiations, good results without scarring were
      noted in all cases except one where a slight inverted scar was developed. The
      effective rate tended to be higher in patients who underwent more irradiation
      treatments and were observed for a longer period of time. Satisfactory cosmetic
      results were achieved after Q-switched ruby laser therapy for nevus of Ota.

PMID- 9143429
TI  - Frontal exostose resection during an endoscopic subperiosteal lifting: case
      report.
AB  - Ever slowly, plastic surgery has adopted minimally invasive procedures in order
      to avoid extensive incisions, large scars, and to obtain better results.
      Endoscopy was introduced into cosmetic surgery of the face in 1992 and it is
      getting more and more widespread as are its indications, often replacing open
      surgical approach. Sometimes, a patient seeking a solution to the stigma attached
      to the aging face may present other problems that are surgically treatable. The
      authors describe a case of surgical endoscopic resection of a frontal osteoma
      during endoscopically assisted brow-lift rhytidoplasty.

PMID- 9143430
TI  - Improving the care of elderly diabetic patients: the final report of the St
      Vincent Joint Task Force for Diabetes.

PMID- 9143431
TI  - Evaluation of treatment for congestive heart failure in patients aged 60 years
      and older using generic measures of health status (SF-36 and COOP charts).
AB  - OBJECTIVES: to assess the functioning and well-being of older patients presenting
      with congestive heart failure (CHF) using established generic health status
      measures-the short form 36 health survey (SF-36) and Dartmouth COOP charts.
      METHODS: patients aged 60 or older with CHF were asked if they would take part.
      They were requested to complete interviewer-administered questionnaires before
      angiotensin converting enzyme (ACE) inhibitor treatment and at follow-up 4 weeks
      later. The interviewer administered the SF-36, COOP charts, the oxygen cost
      diagram and also asked patients to assess their health state overall and, after
      treatment, to assess changes, if any, in overall health. RESULTS: multi
      dimensional health status measures indicate that patient's functioning and well
      being is substantially compromised by CHF, especially in areas relating to
      physical functioning, and that treatment with ACE inhibitors has only limited
      effect in improving health-related quality of life. However, on simple single
      item global assessments of health, patients report that their overall health
      related quality of life is good and many report improvements in overall health
      status at follow-up. CONCLUSIONS: ACE inhibitor treatment, whilst lengthening
      life, has a relatively limited impact on its quality. While multidimensional
      health status measures indicate CHF to be associated with poor health as measured
      by the SF-36 and COOP charts. However, when patients are asked simple single-item
      questions relating to their overall health state and the extent of change
      experienced after treatment, they report relatively good health and positive
      improvements as a consequence of therapy. Since elderly patients' expectations of
      improvement may be modest and their expectations of physical ability relatively
      limited, relatively small improvements, which may not appear large when reported
      in effect size statistics, may be important. Standardized questionnaires, and
      standardized statistical methods of assessing change, may not be appropriate for
      this patient group. A fuller understanding of their expectations and assessment
      of treatment outcomes is necessary.

PMID- 9143432
TI  - Comfortable and maximum walking speed of adults aged 20-79 years: reference
      values and determinants.
AB  - OBJECTIVES: to establish reference values for both comfortable and maximum gait
      speed and to describe the reliability of the gait speed measures and the
      correlation of selected variables with them. DESIGN: descriptive and cross
      sectional. METHODS: subjects were 230 healthy volunteers. Gait was timed over a
      7.62 m expanse of floor. Actual and height normalized speed were determined.
      Lower extremity muscle strength was measured with a hand-held dynamometer.
      RESULTS: mean comfortable gait speed ranged from 127.2 cm/s for women in their
      seventies to 146.2 cm/s for men in their forties. Mean maximum gait speed ranged
      from 174.9 cm/s for women in their seventies to 253.3 cm/s for men in their
      twenties. Both gait speed measures were reliable (coefficients > or = 0.903) and
      correlated significantly with age (r > or = -0.210), height (r > or = 0.220) and
      the strengths of four measured lower extremity muscle actions (r = 0.190-0.500).
      The muscle action strengths most strongly correlated with gait speed were
      nondominant hip abduction (comfortable speed) and knee extension (maximum speed).
      CONCLUSIONS: these normative values should give clinicians a reference against
      which patient performance can be compared in a variety of settings. Gait speed
      can be expected to be reduced in individuals of greater age and of lesser height
      and lower extremity muscle strength.

PMID- 9143433
TI  - Injuries sustained by caregivers of disabled elderly people.
AB  - OBJECTIVE: to investigate the occurrence of physical injury experienced by
      informal caregivers whilst moving and lifting their disabled elderly dependents
      at home. DESIGN: a descriptive study using in-depth interviews. SETTING:
      departments of elderly medicine at two teaching hospitals and one district
      general hospital. SUBJECTS: 46 informal caregivers of elderly patients admitted
      under a regular hospital respite care scheme, 41 of whom were interviewed.
      RESULTS: most caregivers were elderly (median age 70 years), 21 having a medical
      condition which restricted their physical activity. Thirty one caregivers had
      injured themselves whilst lifting and handling their dependents. Most sustained
      back injuries. Eight caregivers were temporarily unable to continue caring as a
      result of the injuries they sustained. Sixteen patients had been injured whilst
      being moved by their caregivers. Only 19 caregivers had received instruction in
      manual handling. CONCLUSION: informal caregivers are often poorly trained and
      equipped and at risk of injury. To enable them to continue providing optimal care
      at home, their physical health should be assessed and they should be trained in
      safe lifting and handling techniques.

PMID- 9143434
TI  - The presence of leuko-araiosis in patients with Alzheimer's disease predicts poor
      tolerance to tacrine, but does not discriminate responders from non-responders.
AB  - BACKGROUND: approximately one-third of patients with Alzheimer's disease (AD)
      respond favourably to the anticholinesterase tacrine, but the drug's usefulness
      is marred by a high incidence of side-effects. OBJECTIVE: to discover if AD
      patients with white matter low attenuation (WMLA) represents a subgroup that
      responds differently to tacrine from those with no WMLA. DESIGN: the results come
      from a combination of double-blind and open studies. Seventy-two AD patients
      prescribed tacrine in our centre were divided into two groups according to the
      presence or absence of WMLA on brain CT scans. We compared the rate of response
      to and withdrawal from tacrine between the groups. Response was defined as an
      improvement in the Mini-Mental State Examination score of three or more points at
      3 months. RESULTS: 18 of the 72 patients were found to have WMLA. There was no
      significant difference in the proportion of patients responding to tacrine in
      each group (28.5% in those with WMLA and 31% in those without), but the rate of
      withdrawal from tacrine did differ: 11 patients with WMLA (61%) had to be
      withdrawn prematurely, compared with 14 patients (26%) in the group without
      evidence of WMLA (P = 0.015). CONCLUSION: AD patients with WMLA can still respond
      to tacrine, although the rate of withdrawal from treatment is much higher in such
      patients.

PMID- 9143435
TI  - Cognitive impairment in medical inpatients. I: Screening for dementia--is history
      better than mental state?
AB  - BACKGROUND: evaluation of the short version of the Informant Questionnaire on
      Cognitive Decline in the Elderly (IQCODE) and the Abbreviated Mental Test (AMT)
      as screening tools for dementia in medical inpatients. METHODS: 201 patients over
      65 were assessed. Assessment included administration of the AMT, a delirium
      screening instrument and a brief psychiatric interview. Relatives were
      interviewed and the IQCODE administered. Diagnostic and Statistical Manual (DSM)
      IIIR diagnoses of various causes of cognitive impairment were made. Sensitivity
      and specificity values of the screening tests for a DSM IIIR diagnosis of
      dementia were calculated. RESULTS: our study suggests that the IQCODE is more
      accurate than the AMT as a screening instrument for dementia. Using a cut-off
      point of > 3.44, sensitivity and specificity of the IQCODE for diagnosing
      dementia were 100 and 86% respectively. Equivalent values for the AMT (cut-off
      point < 8) were 96 and 73%. It was possible to use the IQCODE in eight of the 10
      patients unable to complete the AMT. CONCLUSION: using both the IQCODE and a
      brief cognitive function test when screening for dementia in medical inpatients
      will maximize the number of patients who can be screened.

PMID- 9143437
TI  - Influence of written information on patients' knowledge of their diagnosis.

PMID- 9143436
TI  - Cognitive impairment in medical inpatients. II: Do physicians miss cognitive
      impairment?
AB  - AIM: to study the recognition of cognitive impairment in elderly medical
      inpatients by medical staff. METHODS: 201 patients over 65 were assessed by
      administration of standard cognitive screening tests and an interview with
      relatives. We made Diagnostic and Statistical Manual (DSM) IIIR diagnoses of
      various causes of cognitive impairment and clinical diagnoses for those patients
      not fulfilling DSM IIIR criteria. Medical notes were scrutinized for any mention
      of cognitive impairment. RESULTS: 46% of the patients found to be cognitively
      impaired by the researcher had no record of cognitive impairment in the medical
      notes. However, 14 out of 15 of the patients with DSM IIIR delirium, and 22 out
      of the 26 patients with DSM IIIR dementia, were identified as cognitively
      impaired by the physicians. This suggests that the physicians were detecting the
      vast majority of patients with clinically significant cognitive impairment.

PMID- 9143438
TI  - REM sleep behaviour disorder: a treatable cause of falls in elderly people.

PMID- 9143439
TI  - Dispersion measures in biomedical research on ageing: nuances in the meaning of
      variability.

PMID- 9143440
TI  - Cognitive therapy with elderly people.

PMID- 9143441
TI  - Top-down modulation of early sensory cortex.
AB  - Data from nine previous studies of human visual information processing using
      positron emission tomography were reanalyzed to contrast blood flow responses
      during passive viewing and active discriminations of the same stimulus array. The
      analysis examined whether active visual processing (i) increases blood flow in
      medial visual regions early in the visual hierarchy and (ii) decreases blood flow
      in auditory and somatosensory cortex. Significant modulation of medial visual
      regions was observed in six of nine studies, indicating that top-down processes
      can affect early visual cortex. Modulations showed several task dependencies,
      suggesting that in some cases the underlying mechanism was selective (e.g.
      analysis-or feature-specific) rather than non-selective. Replicable decreases at
      or near auditory Brodmann area (BA) left 41/42 were observed in two of five
      studies, but in different locations. Analyses that combined data across studies
      yielded modest but significant decreases. Replicable decreases were not found in
      primary somatosensory cortex but were observed in an insular region that may be a
      somatosensory association area. Decreases were also noted in the parietal
      operculum (perhaps SII) and BA 40. These results are inconsistent with a model in
      which the precortical input to task-irrelevant sensory cortical areas is broadly
      suppressed.

PMID- 9143442
TI  - Neural dynamics in a model of the thalamocortical system. I. Layers, loops and
      the emergence of fast synchronous rhythms.
AB  - A large-scale computer model was constructed to gain insight into the structural
      basis for the generation of fast synchronous rhythms (20-60 Hz) in the
      thalamocortical system. The model consisted of 65,000 spiking neurons organized
      topographically to represent sectors of a primary and secondary area of mammalian
      visual cortex, and two associated regions of the dorsal thalamus and the thalamic
      reticular nucleus. Cortical neurons, both excitatory and inhibitory, were
      organized in supragranular layers, infraganular layers and layer IV. Reciprocal
      intra- and interlaminar, interareal, thalamocortical, corticothalamic and
      thalamoreticular connections were set up based on known anatomical constraints.
      Simulations of neuronal responses to visual input revealed sporadic epochs of
      synchronous oscillations involving all levels of the model, similar to the fast
      rhythms recorded in vivo. By systematically modifying physiological and
      structural parameters in the model, specific network properties were found to
      play a major role in the generation of this rhythmic activity. For example, fast
      synchronous rhythms could be sustained autonomously by lateral and interlaminar
      interactions within and among local cortical circuits. In addition, these
      oscillations were propagated to the thalamus and amplified by
      corticothalamocortical loops, including the thalamic reticular complex. Finally,
      synchronous oscillations were differentially affected by lesioning forward and
      backward interareal connections.

PMID- 9143443
TI  - Neural dynamics in a model of the thalamocortical system. II. The role of neural
      synchrony tested through perturbations of spike timing.
AB  - Activity in the mammalian thalamocortical system is often accompanied by a
      synchronous discharge of cortical and thalamic neurons. Although many functions
      have been attributed to such synchronous firing, it is not known whether or how
      synchrony of firing per se affects thalamocortical operations. Direct
      experimental tests of the consequences of neuronal synchronization in vivo are
      hard to carry out, whereas theoretical studies based on single-neuron models
      cannot reveal the effects of synchrony at the system level. To overcome these
      limitations, we have used a perturbational approach to test the causal efficacy
      of synchrony per se in large-scale simulations of the thalamocortical system. The
      test consists of selectively disrupting firing synchrony by 'jittering' the
      timing of action potentials in the simulations and determining whether firing
      rates are modified by this perturbation. The simulations are based in detail on
      the known anatomy and physiology of the thalamocortical-visual system of the cat,
      and have been shown in a companion paper to produce episodes of fast synchronous
      activity at multiple levels. By carrying out the perturbation analysis, we
      established that neurons can have long membrane time constants (8-16 ms) and
      balanced synaptic activations, and yet function collectively in such a way that
      synchrony within a time window of 4 ms significantly affects the rates and
      selectivity of the responses to visual stimuli. The simulations also revealed a
      complex interplay, at the network level, between synchrony of firing and rate of
      firing. The dynamic consequences of firing synchrony were most evident when spike
      jittering was applied to specific polysynaptic loops involving corticocortical
      and corticothalamic connections. These results support the view that firing
      synchrony within thalamocortical and corticocortical loops plays a causal role in
      the cooperative and competitive neural interactions that produce pattern
      selective responses in the cortex.

PMID- 9143444
TI  - Model of global spontaneous activity and local structured activity during delay
      periods in the cerebral cortex.
AB  - We investigate self-sustaining stable states (attractors) in networks of
      integrate-and-fire neurons. First, we study the stability of spontaneous activity
      in an unstructured network. It is shown that the stochastic background activity,
      of 1-5 spikes/s, is unstable if all neurons are excitatory. On the other hand,
      spontaneous activity becomes self-stabilizing in presence of local inhibition,
      given reasonable values of the parameters of the network. Second, in a network
      sustaining physiological spontaneous rates, we study the effect of learning in a
      local module, expressed in synaptic modifications in specific populations of
      synapses. We find that if the average synaptic potentiation (LTP) is too low, no
      stimulus specific activity manifests itself in the delay period. Instead,
      following the presentation and removal of any stimulus there is, in the local
      module, a delay activity in which all neurons selective (responding visually) to
      any of the stimuli presented for learning have rates which gradually increase
      with the amplitude of synaptic potentiation. When the average LTP increases
      beyond a critical value, specific local attractors (stable states) appear
      abruptly against the background of the global uniform spontaneous attractor. In
      this case the local module has two available types of collective delay activity:
      if the stimulus is unfamiliar, the activity is spontaneous; if it is similar to a
      learned stimulus, delay activity is selective. These new attractors reflect the
      synaptic structure developed during learning. In each of them a small population
      of neurons have elevated rates, which depend on the strength of LTP. The
      remaining neurons of the module have their activity at spontaneous rates. The
      predictions made in this paper could be checked by single unit recordings in
      delayed response experiments.

PMID- 9143445
TI  - Visual discrimination and short-term memory for random patterns in patients with
      a focal cortical lesion.
AB  - Visual discrimination and short-term recognition memory for computer-generated
      random patterns were explored in 23 patients with a postsurgical lesion in one of
      the cortical hemispheres. Their results are compared with those of 23 age-matched
      volunteers. In a same-different forced-choice discrimination task, d' and log
      beta (measures of sensitivity and bias), as well as reaction time (RT) were
      determined. All participants viewed patterns defined either by luminance contrast
      or isoluminant red-green color contrast, the amplitude of which was adjusted to
      be 10 times the respective detection threshold level. Block patterns consisting
      of a 6 x 6 matrix of light and dark (red and green) checks were randomly
      configured on each presentation. They were presented in pairs, randomly in two
      visual quadrants for a duration of 200 msec. Three presentation conditions were
      used: simultaneous presentation of reference and test stimulus, sequential
      presentation with a short delay (interstimulus interval, ISI = 3 s), and
      sequential presentation with a long delay (ISI = 6 s). The results indicate that
      patients with a lesion in the occipitotemporal cortex, the superior temporal
      cortex and the frontal cortex were significantly impaired on both luminance
      contrast and color-contrast pattern discrimination. Patients with damage in the
      anterior inferotemporal cortex showed no overall impairment. The results suggest
      that performance in visual discrimination and recognition memory tasks rely on
      distributed neural processes with more than one neocortical location.

PMID- 9143446
TI  - Selective aging of the human cerebral cortex observed in vivo: differential
      vulnerability of the prefrontal gray matter.
AB  - In a prospective cross-sectional study, we used computerized volumetry of
      magnetic resonance images to examine the patterns of brain aging in 148 healthy
      volunteers. The most substantial age-related decline was found in the volume of
      the prefrontal gray matter. Smaller age-related differences were observed in the
      volume of the fusiform, inferior temporal and superior parietal cortices. The
      effects of age on the hippocampal formation, the postcentral gyrus, prefrontal
      white matter and superior parietal white matter were even weaker. No significant
      age-related differences were observed in the parahippocampal and anterior
      cingulate gyri, inferior parietal lobule, pericalcarine gray matter, the
      precentral gray and white matter, postcentral white matter and inferior parietal
      white matter. The volume of the total brain volume and the hippocampal formation
      was larger in men than in women even after adjustment for height. Inferior
      temporal cortex showed steeper aging trend in men. Small but consistent rightward
      asymmetry was found in the whole cerebral hemispheres, superior parietal,
      fusiform and orbito-frontal cortices, postcentral and prefrontal white matter.
      The left side was larger than the right in the dorsolateral prefrontal,
      parahippocampal, inferior parietal and pericalcarine cortices, and in the
      parietal white matter. However, there were no significant differences in age
      trends between the hemispheres.

PMID- 9143448
TI  - Chlorofluorocarbon CFCs, potential alternative HCFCs and HFCs, and related
      chlorinated compounds: mass spectral study, Part II.
AB  - In a previous publication, mass spectrometry was applied to the study of several
      ions formed by dissociative ionization of ethanes, partially substituted with
      fluorine and chlorine, and to the determination of the fragmentation pattern of
      each related compound. The aim of the present investigation was to extend this
      mass spectral study (70 eV and low ionization energy) to a group of closely
      related analogs, hydrofluorocarbons (HCFCs), HFCs, chlorinated fluorocarbons, and
      chlorinated hydrocarbons--halogenated methane, ethane, and propane molecules--to
      make an attempt to predict the relative bond strength and then the behavior-
      metabolic pathway and tropospheric degradation--of new HCFCs and HFCs.

PMID- 9143447
TI  - The kinetic occipital region in human visual cortex.
AB  - In the present study we showed that the kinetic occipital (KO) region, located
      laterally in occipital cortex approximately 20 mm behind human MT/V5, can be
      strongly and bilaterally activated under passive viewing conditions. We used
      continuous, randomly changing visual stimulation to compare kinetic gratings to
      uniform motion and kinetic gratings to luminance defined gratings. The KO
      activations under these passive conditions are stronger than those observed when
      the two types of gratings are compared under active conditions, i.e. while
      subjects perform a task (counting gratings of a given orientation). Region KO was
      shown to process both shape and motion information, the conjunction of which is
      typically present in kinetic contours. Area MT/V5 also processes these two
      aspects of visual stimulation but favors motion signals. Clear segregation of
      shape and motion processing was observed only in occipitotemporal and parietal
      regions respectively. Although neurons with properties similar to those derived
      from the conditions activating the KO region have been documented in the macaque
      monkey, their location seems inappropriate for them to correspond to the KO
      activation observed in humans.

PMID- 9143449
TI  - Role of temperature on isoproturon bioaccumulation and effects on two freshwater
      rooted macrophytes: Elodea densa and Ludwigia natans.
AB  - The effects of temperature on the bioaccumulation of the phenylurea herbicide
      isoproturon (IPU) and on the growth inhibition induced on two freshwater rooted
      macrophytes--Elodea densa and Ludwigia natans--were investigated using indoor
      microcosms. The experimental protocol was based on five temperatures (12, 16, 20,
      24, and 28 degrees C) and two contamination levels of the water column (30 and 60
      micrograms IPU.liter-1), plus a control condition. Variations in temperature had
      little effect on the decrease in [IPU] in the water column during the 21-day
      experiment. The IPU concentration in the two macrophyte species was not
      significantly modified by the large range of temperatures when results were
      expressed using the concentration criterion. IPU burdens in the E. densa
      cuttings, on the other hand, increased significantly when the temperature rose
      from 12 to 28 degrees C; small differences were observed between the two exposure
      conditions, in relation to the antagonistic effects of IPU and temperature on the
      growth of the cuttings. Bioconcentration factors in the plants (stems + leaves)
      were close to 10 and 13 after exposure to 30 and 60 micrograms IPU.liter-1,
      respectively.

PMID- 9143450
TI  - Considerations on genetic and environmental factors that contribute to resistance
      or sensitivity of mammals including humans to toxicity of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. Part 1: Genetic factors
      affecting the toxicity of TCDD.
AB  - The marked species differences in short-term toxicity (30-day LD50) of ca. 10,000
      (LD50: guinea pigs ca. 1 microgram/kg body wt and Han/Wistar Kuopio rats more
      than 9600 micrograms/kg body wt) of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is
      one of the central issues of the controversies that have developed on the
      validity of risk assessment strategies for TCDD and related compounds. One of the
      most challenging issues that toxicologists face today is the identification of
      genes that contribute to or are responsible for increased resistance or
      sensitivity to TCDD and related compounds. It is assumed that most, if not all,
      toxic effects of TCDD are mediated more or less through the binding affinity to
      the Ah receptor. This hypothesis was extended and tries to explain the
      differences in sensitivity/resistance of animals including humans to TCDD by
      their total fat (lipid) content. In this respect the gene or genes which is or
      are responsible for obesity of mammals including humans are of great interest. An
      obvious linear positive logarithmic relationship between the oral 30-day LD50
      (microgram/kg) of TCDD in different species and strains of mammals and their
      total body fat content (TBF%) was found: log LD50 = 5.30 x log (TBF)-3.22, or
      LD50 = 0.000603 x (TBF)5.30. By means of this regression the toxicity of TCDD in
      mammals including humans of different age and/or body weight can be predicted if
      their total body fat content is known. Examples of single-gene and polygenic
      disease models in different mammals, such as nonobese diabetic, diabetic, viable
      yellow, obese, and fat mice, as well as transgenic mice, and other suitable
      animal models, such as fatty Zucker rats, Han/Wistar (Kuopio) rats, and minipigs,
      are discussed, and predicted LD50 values of TCDD in these animals and humans are
      presented.

PMID- 9143451
TI  - Effect of dimethoate on photosynthesis and pigment fluorescence of Synechocystis
      sp. PCC 6803.
AB  - The organophosphorus (OP) insecticides are powerful inhibitors of esterases, and
      their toxic actions are commonly explained in terms of acetylcholinesterase (EC
      3.1.1.7) inhibition but their phytotoxic effects remain unexplained. In this
      study the effects of an OP insecticide, dimethoate, on cyanobacterial
      photosynthesis and respiration were measured using the cyanobacterium
      Synechocystis sp. PCC 6803 as test organism. The insecticide caused enhancement
      of respiratory O2 consumption at all tested concentrations (10-300 microM) while
      photosynthesis was found to be significantly affected at concentrations > or = 50
      microM. From fluorescence emission analysis, oxygen exchange measurement, and
      determination of 14CO2 incorporation, it was found that dimethoate caused
      inhibition of photosynthetic electron transport, resulting in increase of PS II
      fluorescence and reduction in photosynthetic carbon fixation. An increase of
      nonphotochemical quenching was caused by the insecticide through the increase in
      acidity of the thylakoid lumen. Furthermore, detachment of phycobilisomes (PBS)
      from the PS II reaction centers was observed in terms of increase in PBS
      fluorescence in treated cultures. This detachment is expected to be caused by
      membrane fluidity changes. The fluorescence enhancement of PS II was more than
      that of the PBS.

PMID- 9143452
TI  - Design and construction of wetlands for aqueous transfers and transformations of
      selected metals.
AB  - Two pilot-scale wetland cells (6.1 x 30.5 m) were integratively designed and
      constructed to emphasize and enhance transfers and transformations of selected
      metals (Cu, Pb, and Zn) in an aqueous matrix. A series of preliminary experiments
      and analyses were conducted to select macrofeatures (hydroperiod, hydrosoil, and
      vegetation) of the constructed wetland system. These wetland cells were designed
      to operate in series or parallel with nominal hydraulic retention times of 24-48
      hr, respectively. With water at a depth of 30 cm, both wetland cells had
      hydrosoil (45 cm) planted with Scirpus californicus. After 250 days of wetland
      operation, average hydrosoil redox potentials in each wetland cell decreased from
      +90 mV to -165 mV, and average plant height increased from 0.3 to 2.7 m. Aqueous
      samples were collected over a 4.5-month period at the inflow and outflow sites of
      the wetland cells. Average inflow concentrations of total recoverable Cu, Pb, and
      Zn were 22.4, 10.5, and 565.9 micrograms/L, respectively. After a 46-hr HRT,
      average outflow concentrations of total recoverable Cu, Pb, and Zn were 15, 2.2,
      and 85.9 micrograms/L, resulting in removals of 33, 79, and 85%, respectively.
      Initial results suggest that these constructed wetlands can be designed to remove
      targeted metals in wastewater.

PMID- 9143453
TI  - Soil ingestion in adults--results of a second pilot study.
AB  - Soil ingestion was evaluated in 10 adults as part of a larger study to evaluate
      soil ingestion in children. Each adult was followed for 4 weeks in a mass-balance
      study that was designed to evaluate the detection limit for soil ingestion in a
      similarly designed, concurrent children's study. After a baseline week, during
      Weeks 2 through 4, adults received daily soil capsules containing 20, 100, and
      500 mg of soil, respectively. A 1-week period separated each study week. Based on
      the first 3 weeks of observation after subtracting the capsule ingestion amounts,
      the median, 75th percentile, and 95th percentile soil ingestion estimates were 1,
      49, and 331 mg/day, with estimates calculated as the median of the three trace
      elements Al, Si, and Y. The average estimate of soil ingestion was 10 mg/day (SD
      = 94 mg/day). These findings augment sparse empirical data on adult soil
      ingestion, and suggest lower levels of soil ingestion in adults than previous
      studies.

PMID- 9143454
TI  - Soil ingestion estimates for children residing on a superfund site.
AB  - Soil ingestion estimates were obtained from a stratified, simple random sample of
      64 children aged 1-4 years residing on a superfund site in Montana. The study was
      conducted during the month of September for 7 consecutive days. The study
      utilized a mass-balance methodology in which eight naturally occurring soil
      tracers (Al, Si, Ti, Ce, Nd, La, Y, and Zr) believed to be poorly absorbed by the
      gastrointestinal tract were employed to provide soil ingestion estimates. Food
      and fecal samples were analyzed on a daily basis. Soil/dust samples
      representative of where the children played during the study period were
      obtained. Very high compliance among the participants was maintained throughout
      the study. The identical methodology employed in the childrens' study was used in
      an adult study of tracer recovery in 10 subjects over 28 days of observation to
      provide validation that soil ingestion over the range of 20 to 500 mg/day could
      be detected. Soil ingestion was estimated by each soil tracer via traditional
      methods as well as by an improved approach using five trace elements (Al, Si, Ti,
      Y, and Zr), called the Best Tracer Method (BTM), which substantially corrects for
      error due to misalignment of tracer input and output as well as error occurring
      from ingestion of tracers from nonfood, nonsoil sources, while being insensitive
      to the particle size of the soil/dust ingested. According to the BTM, the median
      soil ingestion was less than 1 mg/day while the upper 95% was 160 mg/day. No
      significant age (1 year vs 2, vs 3) or sex-related differences in soil ingestion
      were observed. These estimates are lower than estimates observed in another study
      in Massachusetts during September and October. Significant methodological
      improvements in this study as compared to previously conducted soil ingestion
      studies include the selection of a representative sample of children, longer
      study duration, inclusion of dietary recommendations to reduce food tracer input
      and variability, use of the BTM, and a stronger adult validation study with
      respect to number of subjects, and duration and range of possible soil ingestion
      rates. Despite these methodological improvements, evidence exists that this study
      displays a net residual negative error, suggesting that the above estimates are
      below the true soil ingestion. The magnitude of this residual negative error
      cannot be quantified with the BTM but is likely to not affect the median by more
      than 40 mg/day, while the impact of such an error on the upper end of the
      distribution is more uncertain.

PMID- 9143455
TI  - The toxicity of substituted phenolic compounds to a detoxifying and an acetic
      acid bacterium.
AB  - In the detoxifying bacterium Acinetobacter calcoaceticus 69-V and in the acetic
      acid bacterium Acetobacter methanolicus MB 58, glucose and xylose are oxidized,
      respectively, via PQQ-dependent membrane-bound dehydrogenases, which are linked
      to the respiratory chain in a manner enabling energy conservation via electron
      transport phosphorylation (ETP) in the cytoplasmic membrane. Neither the glucose
      and gluconic acid nor the xylose and xylonic acid are metabolized. Therefore,
      measurements of sugar oxidation-driven ATP syntheses ought not to be disturbed by
      ATP drainage caused by anabolic processes. Studying the effect of substituted
      phenolic compounds on these energization processes reveals that their toxicity
      increases with an increasing degree of chlorination and that A. calcoaceticus 69
      V is more stable than A. methanolicus MB 58 against chlorinated phenols. On the
      other hand, A. methanolicus MB 58 is more stable against 2,4-dinitrophenol (2,4
      DNP) and 2,4-dichlorophenoxyacetic acid (2,4-D), especially in the acidic pH
      range, in which the sensitivity of ATP synthesis to the uncouplers is higher than
      that of respiration. The toxicity caused by protonophoric activities ought to be
      barely detectable by respiratory and dehydrogenase tests. The luminescence system
      of Photobacterium phosphoreum tested in the luminescent bacteria test was much
      more sensitive. This test system should be used as a screening tool and the
      effects measured must be confirmed by toxicity tests evaluating the stability of
      bacteria themselves involved in processes of detoxification as well as the
      production of toxic metabolites, monitored with respect to their velocity and
      efficiency.

PMID- 9143456
TI  - Ecosystem recovery following selenium contamination in a freshwater reservoir.
AB  - Belews Lake, North Carolina, was contaminated by selenium in wastewater released
      from a coal-fired electric generating facility during 1974-1985. Selenium
      bioaccumulated in aquatic food chains and caused severe reproductive failure and
      teratogenic deformities in fish. Beginning in 1986, the electric utility company
      changed its ash disposal practices and selenium-laden wastewater no longer
      entered the lake. A survey of selenium present in the water, sediments, benthic
      invertebrates, fish, and aquatic birds was conducted in 1996. Concentrations were
      compared to pre-1986 levels to determine how much change occurred during the
      decade since selenium inputs stopped. The data were also examined using a hazard
      assessment protocol to determine if ecosystem-level hazards to fish and aquatic
      birds had changed as well. Results reveal that waterborne selenium fell from a
      peak of 20 micrograms/liter before 1986, to < 1 microgram/liter in 1996;
      concentrations in biota were 85-95% lower in 1996. Hazard ratings indicate that
      high hazard existed prior to 1986 and that moderate hazard is still present,
      primarily due to selenium in the sediment-detrital food pathway. Concentrations
      of selenium in sediments have fallen by about 65-75%, but remain sufficiently
      elevated (1-4 micrograms/g) to contaminate benthic food organisms of fish and
      aquatic birds. Field evidence confirmed the validity of the hazard ratings.
      Developmental abnormalities in young fish indicate that selenium-induced
      teratogenesis and reproductive impairment are occurring. Moreover, the
      concentrations of selenium in benthic food organisms are sufficient to cause
      mortality in young bluegill and other centrarchids because of Winter Stress
      Syndrome. At the ecosystem level, recovery has been slow. Toxic effects are still
      evident 10 years after selenium inputs were stopped. The sediment-associated
      selenium will likely continue to be a significant hazard to fish and aquatic
      birds for years.

PMID- 9143457
TI  - Selenium-induced growth reduction in Brassica land races considered for
      phytoremediation.
AB  - Brassica species considered for use in selenium (Se) phytoremediation need to
      accumulate large amounts of Se to be successful. Retarded plant growth and
      impaired protein synthesis are common symptoms for plants grown under
      seleniferous soils. Selenium accumulation by different land races of Brassica
      juncea (L.) Czern and Coss and one land race of Brassica carinata was
      investigated in Se-enriched water and soil cultures containing 2 mg Se kg-1.
      Effects of Se concentration in the root environment on the assimilation of Se,
      leaf surface area, dry matter yield, total leaf protein concentration, and free
      seleno-amino acid concentrations were analyzed for plants grown in Se-laden
      media. In water culture, shoot Se concentrations among the land races ranged from
      501 to 1017 mg Se kg-1 dry matter (DM), and in plants grown in Se-laden soil,
      concentrations ranged from 407 to 769 mg Se kg-1 DM. Land races grown with Se
      exhibited decreases in dry matter yields from 12 to 23% and in leaf surface area
      from 5 to 26% compared to the same land races grown without Se. Protein content
      was significantly correlated both with shoot Se concentrations (r = 0.746, P <
      0.001) and with leaf surface area (r = 0.446, P < 0.01) for all land races grown
      in Se-enriched water culture. There was also a significant correlation (r =
      0.767, P < 0.001) between total Se assimilation and shoot protein for all land
      races. Free selenomethionine was detected for plants grown with Se and ranged
      from 92 to 958 ng g-1 DM. Other seleno-amino acids, Se-methyl-selenocysteine and
      selenocysteine, were not consistently detected as free amino acids in the
      different land races. Although visual symptoms of Se toxicity were not observed
      in the Brassica species, dry matter yield, leaf surface, and total shoot protein
      decreased, depending on the land races tested.

PMID- 9143458
TI  - Stream periphytic biodegradation of the anionic surfactant C12-alkyl sulfate at
      environmentally relevant concentrations.
AB  - The effects of continuous exposure to C12-alkyl sulfate on a periphytic microbial
      community were determined in an 8-week stream mesocosm study. C12-alkyl sulfate
      concentrations ranged from environmentally relevant (< 10-20 micrograms/liter) to
      unrealistically high concentrations (> 1500 micrograms/liter). Endpoints
      evaluated included turnover rates, bacterial cell density, heterotrophic mixed
      amino acid uptake, and fatty acid profile evaluations. Predosed periphyton
      demonstrated a mean turnover rate for C12-alkyl sulfate of 0.08/hr. During the 8
      week dosing period, a significant increase in mean turnover rates was observed in
      streams dosed with > or = 61 micrograms C12-alkyl sulfate/liter, despite a 10
      degrees C drop in stream temperature. A significant correlation between turnover
      rate and C12-alkyl sulfate concentration was also observed. While bacterial cell
      density increased during the study, it was determined that the biodegradation
      acclimation to C12-alkyl sulfate was not biomass-specific. Likewise, bacterial
      activity generally increased over the study, but it did not correlate with either
      biodegradation or bacterial cell density. Lastly, phospholipid fatty acid
      profiles indicate that a shift in the microbial community occurred in the high
      dose stream as opposed to the control stream. This study demonstrates that C12
      alkyl sulfate is rapidly degraded and induces a biodegradative acclimation
      response at environmentally relevant concentrations.

PMID- 9143459
TI  - Parathyroid imaging with technetium-99m labelled cationic complexes: which tracer
      and which technique should be used?

PMID- 9143460
TI  - Intraoperative nuclear guidance in benign hyperparathyroidism and parathyroid
      cancer.
AB  - The success of parathyroid surgery is determined by the identification and
      removal of all hyperactive parathyroid tissue. Ectopic location of parathyroid
      tumours and fibrosis due to previous operations can cause failure of
      parathyroidectomy. Parathyroid tumours accumulate and retain 2
      methoxyisobutylisonitrile (MIBI) labelled with technetium-99m. This study
      assesses the value of intra-operative localization of parathyroid tumours using a
      hand-held gamma detector in patients with hyperparathyroidism and parathyroid
      cancer. Twenty patients undergoing their first operations for
      hyperparathyroidism, 15 patients undergoing reoperations for either persistent or
      recurrent hyperparathyroidism and two patients with parathyroid cancer were
      studied. Radioactivity in the neck and the mediastinum was recorded by a gamma
      detector after administration of 370 MBq 99m Tc-MIBI. Surgical findings and
      postoperative serum levels of calcium were documented. The sensitivity of the
      gamma detector in identifying parathyroid tumours was 90.5% in first
      parathyroidectomies, 88.9% in reoperations for either persistent or recurrent
      hyperparathyroidism and 100% in parathyroid cancer. One false-positive result was
      due to a thyroid nodule. Hypercalcaemia ceased in all but one patient
      postoperatively. It is concluded that employment of the gamma detector is to be
      advocated in first parathyroidectomies when a parathyroid tumour cannot be
      discovered, in reoperations for either persistent or recurrent
      hyperparathyroidism and in surgery for parathyroid cancer.

PMID- 9143461
TI  - Clinical significance of thallium-201 and gallium-67 scintigraphy in pulmonary
      tuberculosis.
AB  - One hundred and thirty-nine patients with pulmonary tuberculosis were evaluated
      by means of gallium-67 and thallium-201 scintigraphy. The disease was clinically
      active in 83 and inactive in 56. The uptake ratio between the lesion and the
      contralateral normal lung field was calculated. The ratio determined by 67Ga
      scintigraphy was expressed as GR, and that determined by 201T1 scintigraphy
      (early or delayed) as ER or DR. The 201T1 retention index (RI) was calculated
      using the following equation: RI = DR - ER/ER x 100. The sensitivity, specificity
      and accuracy of 201T1 scintigraphy with respect to the activity of pulmonary
      tuberculosis were better than those of 67Ga scintigraphy (the figures for 201T1
      scintigraphy were 88.0%, 82.1% and 85.6%, respectively, and those for 67Ga
      scintigraphy, 83.1%, 60.7% and 74.1%). We found a significant correlation between
      GR and ER, but there was no significant correlation between RI and ER. When the
      relationships between ER, C-reactive protein and 1-h erythrocyte sedimentation
      rate were examined among patients with abnormal uptake, no significant
      relationships were noted. In the 27 patients who could be followed up, GR and ER
      decreased with duration of the therapy, indicating a decrease in disease activity
      which was consistent with clinical findings. The RI was significantly higher in
      the early stages of therapy than in the later stages (P < 0.01), suggesting a
      temporary delay in 201T1 washout in the early stages. The washout seemed to be
      promoted by the effects of the therapy. Overall, it is concluded that 201T1
      scintigraphy is more useful and more suitable than 67Ga scintigraphy for the
      evaluation of disease activity and therapeutic effects in patients with pulmonary
      tuberculosis.

PMID- 9143462
TI  - Bayesian image reconstruction for emission tomography based on median root prior.
AB  - The aim of the present study was to investigate a new type of Bayesian one-step
      late reconstruction method which utilizes a median root prior (MRP). The method
      favours images which have locally monotonous radioactivity concentrations. The
      new reconstruction algorithm was applied to ideal simulated data, phantom data
      and some patient examinations with PET. The same projection data were
      reconstructed with filtered back-projection (FBP) and maximum likelihood
      expectation maximization (ML-EM) methods for comparison. The MRP method provided
      good-quality images with a similar resolution to the FBP method with a ramp
      filter, and at the same time the noise properties were as good as with Hann
      filtered FBP images. The typical artefacts seen in FBP reconstructed images
      outside of the object were completely removed, as was the grainy noise inside the
      object. Quantitatively, the resulting average regional radioactivity
      concentrations in a large region of interest in images produced by the MRP method
      corresponded to the FBP and ML-EM results but at the pixel by pixel level the MRP
      method proved to be the most accurate of the tested methods. In contrast to other
      iterative reconstruction methods, e.g. ML-EM, the MRP method was not sensitive to
      the number of iterations nor to the adjustment of reconstruction parameters. Only
      the Bayesian parameter beta had to be set. The proposed MRP method is much more
      simple to calculate than the methods described previously, both with regard to
      the parameter settings and in terms of general use. The new MRP reconstruction
      method was shown to produce high-quality quantitative emission images with only
      one parameter setting in addition to the number of iterations.

PMID- 9143463
TI  - Effect of attenuation correction on myocardial thallium-201 distribution in
      patients with a low likelihood of coronary artery disease.
AB  - Regional variation of tracer distribution is seen in uncorrected thallium-201
      images of normal hearts. This study evaluates the effect of attenuation
      correction on myocardial 201T1 distribution in patients with low risk of coronary
      artery disease. An L-shaped dual-detector single-photon emission tomographic
      system equipped with a pair gadolinium-153 scanning line sources was used for
      sequential emission/transmission imaging in 36 patients (14 men and 22 women)
      with less than 5% risk for coronary artery disease. Uncorrected emission images
      were reconstructed using filtered back-projection (FBP) whereas the attenuation
      corrected (AC) images were iteratively reconstructed using the attenuation map
      computed from the transmission data. Both sets of images were reorientated into
      short axis, vertical long axis and horizontal long axis images. For
      quantification data were reconstructed into polar plots and count density
      estimated in 17 myocardial segments. The population % standard deviation for each
      segment of AC data was significantly smaller than that for FBP data, indicating
      improved homogeneity of tracer distribution. In men the anterior-basal inferior
      activity ratio improved from 1.20 for FBP to 0.96 for AC (stress) and from 1.23
      for FBP to 0.98 for AC (delay) (P < 0.0001). In women the anterior-basal inferior
      activity ratio changed from 1.08 for FBP to 0.94 for AC (stress) and from 1.08
      for FBP to 0.93 for AC (delay) (P < 0.001). These ratios reflect appropriate
      compensation for basal attenuation but a lack of scatter correction. The lateral
      septal activity ratio in men changed from 1.05 for FBP to 0.99 for AC (stress)
      and from 1.02 for FBP to 0.96 for AC (delay), while in women it changed from 1.05
      for FBP to 0.98 for AC (stress) and from 1.04 for FBP to 0.98 for AC (delay) (P <
      0.005 in all cases). The apex of AC images showed a decrease in activity
      consistent with wall thining at this site. It is concluded that the use of
      attenuation correction yields improved homogeneity of myocardial tracer
      distribution in patients with low risk of coronary artery disease. The diagnostic
      benefits of attenuation correction are yet to be fully assessed.

PMID- 9143464
TI  - Cardiac phase-synchronized myocardial thallium-201 single-photon emission
      tomography using list mode data acquisition and iterative tomographic
      reconstruction.
AB  - The purpose of this study was to determine whether data acquisition in the list
      mode and iterative tomographic reconstruction would render feasible cardiac phase
      synchronized thallium-201 single-photon emission tomography (SPET) of the
      myocardium under routine conditions without modifications in tracer dose,
      acquisition time, or number of steps of the a gamma camera. Seventy non-selected
      patients underwent 201T1 SPET imaging according to a routine protocol (74 MBq/2
      mCi 201T1, 180 degrees rotation of the gamma camera, 32 steps, 30 min). Gamma
      camera data, ECG, and a time signal were recorded in list mode. The cardiac cycle
      was divided into eight phases, the end-diastolic phase encompassing the QRS
      complex, and the end-systolic phase the T wave. Both phase- and non-phase
      synchronized tomograms based on the same list mode data were reconstructed
      iteratively. Phase-synchronized and non-synchronized images were compared.
      Patients were divided into two groups depending on whether or not coronary artery
      disease had been definitely diagnosed prior to SPET imaging. The numbers of
      patients in both groups demonstrating defects visible on the phase-synchronized
      but not on the non-synchronized images were compared. It was found that both
      postexercise and redistribution phase tomograms were suited for interpretation.
      The changes from end-diastolic to end-systolic images allowed a comparative
      assessment of regional wall motility and tracer uptake. End-diastolic tomograms
      provided the best definition of defects. Additional defects not apparent on non
      synchronized images were visible in 40 patients, six of whom did not show any
      defect on the non-synchronized images. Of 42 patients in whom coronary artery
      disease had been definitely diagnosed, 19 had additional defects not visible on
      the non-synchronized images, in comparison to 21 of 28 in whom coronary artery
      disease was suspected (P < 0.02; chi 2). It is concluded that cardiac phase
      synchronized 201T1 SPET of the myocardium was made feasible by list mode data
      acquisition and iterative reconstruction. The additional findings on the phase
      synchronized tomograms, not visible on the non-synchronized ones, represented
      genuine defects. Cardiac phase-synchronized 201T1 SPET is advantageous in
      allowing simultaneous assessment of regional wall motion and tracer uptake, and
      in visualizing smaller defects.

PMID- 9143465
TI  - Feasibility of simultaneous dual-isotope myocardial perfusion acquisition using a
      lower dose of sestamibi.
AB  - The feasibility of simultaneous dual-isotope myocardial perfusion imaging was
      assessed using a ca. 12 mCi dose of technetium-99m sestamibi (MIBI) and ca. 3 mCi
      thallium-201. Planar and single-photon emission tomographic (SPET) data from 40
      patients (41 studies) imaged with both a single- and a dual-isotope protocol were
      analyzed. Rest injected 201T1 (pure-T1) images were acquired using 20% windows at
      70 and 166 keV about 15 min after the 201T1 injection. Patients were then
      stressed, and at peak stress 99mTc-sestamibi was injected. About 30 min later
      99mTc data were recorded with a 20% window center at 140 keV, and simultaneous
      201T1 (dual-T1) data were recorded with a single 20% window centered at 80 keV.
      Total myocardial counts based on SPET data in the dual-T1 images were increased
      by 18.61% +/- 2.91% (SEM) (range: -12.8% to 84.1%) compared to pure-T1 images.
      Region of interest analysis revealed the greater increase in counts in the apical
      region and the least in the lateral wall. Pure T1 and dual-T1 images were
      visually evaluated for image quality (IQ) on a five-point scale (0 = unacceptable
      to 4 = excellent). Dual-T1 IQ was lower than that of pure-T1 in 61% of cases, and
      similar in 37% (12% of the pure-T1 and 41% of the dual-T1 images fell into the 0
      and 1 categories). Thallium perfusion abnormalities were of similar extent in 70%
      of segments, less severe in 18%, and more severe in 12%. There was an inverse
      correlation with patient weight, such that patients weighing more than 180 lbs
      had substantially worse images than those below this cutoff value. While dual
      tracer images are of lower quality, they are interpretable if the patient is not
      severely overweight.

PMID- 9143466
TI  - Detection of radiation-induced myocardial damage by technetium-99m sestamibi
      scintigraphy.
AB  - A prospective study was initiated to assess the side-effects of postoperative
      adjuvant radiotherapy in patients with left-sided early breast cancer. Twelve
      patients with early breast cancer were examined before and a year after
      radiotherapy. Echocardiography, ECG and bicycle ergometry stress test with
      technetium-99m sestamibi myocardial perfusion scintigraphic were carried out to
      assess changes in regional myocardial blood flow. Six of the 12 patients had new
      fixed scintigraphic defects after radiotherapy (as compared with the preradiation
      examination). The localization of the defects corresponded well with the
      irradiated volume of the left ventricle. These defects were probably due to
      microvascular damage to the myocardium. Neither ECG changes nor left ventricular
      segmental wall motion abnormalities could be detected by echocardiography. To our
      knowledge this study is the first to show that radiation-induced micro-vascular
      damage to the myocardium may be detected by perfusion scintigraphy. This may
      limit the use of scintigraphy in diagnosing coronary artery disease in patients
      treated with thoracic radiotherapy. Long-term follow-up is necessary to assess
      whether the presence of microvascular damage is a prognostic sign for the
      development of radiation-induced coronary artery disease.

PMID- 9143467
TI  - Clinical evaluation of the partition model for estimating radiation doses from
      yttrium-90 microspheres in the treatment of hepatic cancer.
AB  - Radiation doses to the tumour and non-tumorous liver compartments from yttrium-90
      microspheres in the treatment of hepatic cancer, as estimated by a partition
      model, have been verified by correlation with the actual doses measured with a
      beta probe at open surgery. The validity of the doses to the lungs, the tumour
      and non-tumorous liver compartment as estimated by the partition model was
      further evaluated in clinical settings. On the basis of the observation that one
      of three patients who received more than 30 Gy from a single treatment and one of
      two patients who received more than 50 Gy from multiple treatments developed
      radiation pneumonitis, it was deduced that an estimated lung dose < 30 Gy from a
      single treatment and a cumulative lung dose < 50 Gy from multiple treatments were
      probably the tolerance limits of the lungs. Three of five patients who received
      lung doses > 30 Gy as estimated by the partition model and were predicted to
      develop radiation pneumonitis, did so despite the use of partial hepatic
      embolization to reduce the degree of lung shunting. Furthermore, a higher
      radiological response rate and prolonged survival were found in the group of
      patients who received higher tumour doses, as estimated by the partition model,
      than in the group with lower estimated tumour doses. Thus the radiation doses
      estimated by the partition model can be used to predict (a) complication rate,
      (b) response rate and (c) duration of survival in the same manner as the actual
      radiation doses measured with a beta probe at open surgery. The partition model
      has made selective internal radiation therapy using 90Y microspheres safe and
      repeatable without laparotomy.

PMID- 9143468
TI  - Evaluation of two population-based input functions for quantitative neurological
      FDG PET studies.
AB  - The conventional measurement of the regional cerebral metabolic rate of glucose
      (rCMRGlc) with fluorodeoxyglucose (FDG) and positron emission tomography (PET)
      requires arterial or arterialised-venous (a-v) blood sampling at frequent
      intervals to obtain the plasma input function (IF). We evaluated the accuracy of
      rCMR-Glc measurements using population-based IFs that were calibrated with two a
      v blood samples. Population-based IFs were derived from: (1) the average of a-v
      IFs from 26 patients (Standard IF) and (2) a published model of FDG plasma
      concentration (Feng IF). Values for rCMRGlc calculated from the population-based
      IFs were compared with values obtained with IFs derived from frequent a-v blood
      sampling in 20 non-diabetic and six diabetic patients. Values for rCMRGlc
      calculated with the different IFs were highly correlated for both patient groups
      (r > or = 0.992) and root mean square residuals about the regression line were
      less than 0.24 mg/min/100 g. The Feng IF tended to underestimate high rCMRGlc.
      Both population-based IFs simplify the measurement of rCMRGlc with minimal loss
      in accuracy and require only two a-v blood samples for calibration. The reduced
      blood sampling requirements markedly reduce radiation exposure to the blood
      sampler.

PMID- 9143469
TI  - Thallium-201 single-photon emission tomography in the treatment follow-up of
      nasopharyngeal carcinoma.
AB  - In order to assess the usefulness of thallium-201 single-photon emission
      tomography (SPET) in the treatment follow-up of nasopharyngeal carcinoma (NPC), a
      total of 75 201T1 SPET studies were performed in 18 patients with histologically
      proven NPC. The findings were compared with those of magnetic resonance imaging
      (MRI) before and after therapy. Four patients received radiotherapy alone while
      the other 14 received concurrent chemo-radiotherapy. Treatment response was
      classified as complete (CR) or partial (PR) based on the findings of MRI and
      201T1 SPET. Intense 201T1 uptake by the tumour was seen in all 18 patients before
      treatment. After treatment, MRI showed seven CRs and 11 PRs, whereas 201T1 SPET
      showed 13 CRs and five PRs. In 12 patients, the results of 201T1 SPET were in
      agreement with those of MRI. In six patients MRI showed PR but 201T1 showed CR.
      Follow-up (mean 10.6 months) MRI and 201T1 SPET studies of these six patients
      revealed that tumour gradually decreased and finally vanished in three patients.
      This preliminary study indicates that 201T1 SPET has potential in the assessment
      of early response to treatment of patients with NPC when compared with MRI.

PMID- 9143470
TI  - Comparison of indium-111 octreotide and thallium-201 scintigraphy in patients
      mammographically suspected of having breast cancer: preliminary results.
AB  - Indium-111 octreotide and thallium-201 scintigraphic studies were compared in 21
      patients (16 with palpable and five with non-palpable lesions) suspected of
      having breast malignancies on the basis of mammography. Early (15 min) and late
      (3 h) 201Tl (111 MBq) and 4-h and 24-h 111In-octreotide (111-148 MBq) static
      planar anterior images (matrix 256 x 256) were obtained on separate days. Images
      were evaluated both visually and quantitatively. Biopsy was performed following
      the imaging studies. Histopathology revealed 17 breast carcinomas (15 cases of
      invasive ductal carcinoma, one mucinous adenocarcinoma and one intraductal
      carcinoma) and four benign breast lesions (two fibroadenomas, one abscess and one
      case of fat necrosis). The means histopathological tumour size (mean largest
      diameter) was 3.38 +/- 1.9 cm. 111In-octreotide detected 16 of the 17 breast
      cancers (94%) while 201Tl detected 13 of them (76%). Both 111In-octreotide and
      201Tl missed one non-palpable carcinoma showing only an isolated cluster of
      microcalcifications on mammography. The smallest tumour size detected by both
      agents 1.5 x 1.5 cm. Of the four benign lesions, only the breast abscess revealed
      both 201Tl and 111In-octreotide uptake. 111In-octreotide scan also showed tracer
      uptake in five of the six patients with histologically proven axillary
      metastases, while four of these six patients showed 201Tl uptake. The
      tumour/background (T/B) ratios of late 111In-octreotide and 201Tl images were
      1.71 +/- 0.38 and 1.46 +/- 0.30 respectively (P = 0.039). In this preliminary
      study, 111In-octreotide yielded more favourable results than 201Tl in the
      detection of breast carcinomas. However, the diagnostic efficacy of 111In
      octreotide imaging needs to be investigated in larger patient series.

PMID- 9143471
TI  - Structural modification of receptor-binding technetium-99m complexes in order to
      improve brain uptake.
AB  - Low brain uptake is a generally accepted problem in developing technetium-99m
      brain receptor imaging agents. For a class of potential 5-HT2A receptor-binding
      agents we tried to improve the original low brain uptake of 0.4% injected dose
      (ID) in rats 5 min p.i. by modifying the lipophilic properties of the molecules.
      Because of the presence of a protonable nitrogen, which according to the pKa
      value leads to ionization of the molecule at blood pH, the pKa value was
      considered to be the parameter most suitable for adjustment of lipophilicity.
      Insertion of ether-oxygen in the molecule of five candidates lowers the apparent
      pKa value from 10.0 to 8.3 and dramatically increases the brain uptake to 1.3% ID
      at 5 min. The direct relationship between brain uptake and apparent pKa cannot be
      simply explained by the increase in the pKa-governed proportion of the neutral
      species.

PMID- 9143472
TI  - Brain perfusion scintigraphy with 99mTc-HMPAO or 99mTc-ECD and 123I-beta-CIT
      single-photon emission tomography in dementia of the Alzheimer-type and diffuse
      Lewy body disease.
AB  - Dementia of the Alzheimer-type (DAT) is characterized by progressive cognitive
      decline, variably combined with frontal lobe release signs, parkinsonian symptoms
      and myoclonus. The features of diffuse Lewy body disease (DLBD), the second most
      common cause of degenerative dementia, include progressive cognitive
      deterioration, often associated with levodopa-responsive parkinsonism,
      fluctuations of cognitive and motor functions, psychotic symptoms (visual and
      auditory hallucinations, depression), hypersensitivity to neuroleptics and
      orthostatic hypotension. A recent report suggests that positron emission
      tomography studies in patients with degenerative dementia may be useful in the
      differential diagnosis of DAT and DLBD. However, the diagnostic role of single
      photon emission tomography (SPET) studies remains to be established. The aim of
      this study was therefore to evaluate regional cerebral perfusion [with either
      technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) or 99mTc-ethyl
      cysteinate dimer (99mTc-ECD) SPET] and striatal dopamine transporter density
      [using iodine-123 2 beta-carboxymethoxy-3 beta-[4-iodophenyl]tropane (123I-beta
      CIT) SPET] in patients with DAT and DLBD. Six patients with probable DAT and
      seven patients with probable DLBD were studied. Blinded qualitative assessment by
      four independent raters of 99mTc-HMPAO or 99mTc-ECD SPET studies revealed
      bilateral temporal and/or parietal hypoperfusion in all DAT patients. There was
      additional frontal hypoperfusion in two patients and occipital hypoperfusion in
      one patient. In the DLBD group, regional cerebral perfusion had a different
      pattern. In addition to temporoparietal hypoperfusion there was occipital
      hypoperfusion resembling a horseshoe defect in six of seven patients. In the DAT
      group, the mean 3-h striatal/cerebellar ratio of 123I-beta-CIT binding was 2.5 +/
      0.4, with an increase to 5.5 +/- 1.1 18 h after tracer injection. In comparison,
      in the DLBD patients the mean 3-h striatal/cerebellar ratio of 123I-beta-CIT
      binding was significantly reduced to 1.7 +/- 0.3, with a modest increase to 2.1
      +/- 0.4 18 h after tracer injection (P < 0.05, Scheffe test, ANOVA). These
      results suggest that 99mTc-HMPAO or 99mTc-ECD and 123I-beta-CIT SPET may
      contribute to the differential diagnosis between DAT and DLBD, showing different
      perfusion patterns and more severe impairment of dopamine transporter function in
      DLBD than in DAT.

PMID- 9143473
TI  - Parathyroid scintigraphy: first experiences with technetium (III)-99m-Q12.
AB  - We report the preliminary results of a prospective study demonstrating
      technetium(III)-99m furifosmin (Q12) uptake in histologically proven parathyroid
      adenomas. Scintigraphy was performed in 12 patients with hyperparathyroidism. Q12
      correctly identified the parathyroid adenomas by focal prolonged tracer retention
      in ten of the 12 patients. In the two patients without localized tracer
      retention, no parathyroid adenoma could be identified surgically, either. The
      retention half-times ranged from 0.5 to 1.8 h (mean 1.27) in the parathyroid
      adenomas and from 0.3 to 1.2 h (mean 1.05) in the thyroid gland. Our preliminary
      results show that Q12 is a feasible, sensitive tracer for parathyroid
      scintigraphy. In comparison to sestamibi (MIBI) and tetrofosmin, Q12 displays
      short retention in the thyroid gland, which would seem rather advantageous.
      Further evaluation is needed to determine which among Q12, tetrofosmin and MIBI
      is most sensitive for the detection especially of small parathyroid adenomas, and
      which tracer properties will best reflect the degree of endocrine activity.

PMID- 9143474
TI  - Iodine-123 labelled radiopharmaceuticals and single-photon emission tomography: a
      natural liaison.
AB  - Most nuclear medicine departments possess one or more imaging apparatuses for
      single-photon emission tomography (SPET). Molecules of biological interest to
      assess metabolism and receptor function are often labelled with 123I, which
      allows proper SPET imaging. The various methods for radiolabelling are reviewed.
      As the biological integrity of these agents has been demonstrated for numerous
      radiopharmaceuticals, the purpose of this review is to summarize the efficacy in
      various fields of medicine, including the imaging of tumours, infection,
      myocardium and cerebrum.

PMID- 9143475
TI  - Estimation of age-dependent effective dose coefficients for nitrogen-13 L
      glutamate.

PMID- 9143476
TI  - Differences between technetium-99m tetrofosmin and technetium-99m sestamibi in
      parathyroid scintigraphy.

PMID- 9143477
TI  - Comparison of PET, SPET, neuropsychological and morphological findings in
      vascular dementia.

PMID- 9143478
TI  - The three-step pretargeting approach reduces the human anti-mouse antibody
      response in patients submitted to radioimmunoscintigraphy and radioimmunotherapy.

PMID- 9143479
TI  - Isopropanol vapor inhalation oncogenicity study in Fischer 344 rats and CD-1
      mice.
AB  - The potential oncogenic effects of isopropanol, a widely used solvent, were
      investigated. Four groups of animals, each consisting of 75 CD-1 mice/sex and 75
      Fischer 344 rats/sex, were exposed to isopropanol vapor (CAS No. 67-63-0) at
      target concentrations of 0 (filtered air control), 500, 2500, or 5000 ppm.
      Animals assigned to the core group (55 mice/sex/group and 65 rats/sex/group) were
      exposed for 6 hr/day, 5 consecutive days/week for at least 78 weeks for the mice
      or 104 weeks for the rats. Ten mice/sex/group and 10 rats/sex/group were assigned
      to an interim euthanasia group and were terminated during Weeks 54 and 73,
      respectively. In addition, 10 mice/sex/group were assigned to a recovery group
      and did not receive any further exposure following Week 53 but were retained
      until the core group of animals was euthanized. Transient signs of narcosis were
      observed for both mice and rats during exposure to 2500 and 5000 ppm and
      following exposure for mice from the 5000-ppm group. Increased mortality (100%
      versus 82% for controls) and a decreased mean survival time (577 days versus 631
      days for controls) were noted for male rats from the 5000-ppm group. Increases in
      body weight and/or body weight gain were typically observed for both sexes of
      mice and rats from the 2500- and 5000-ppm groups throughout the study. Urinalysis
      and urine chemistry changes indicative of impaired kidney function (i.e.,
      decreased osmolality and increased total protein, volume, and glucose) were noted
      for male rats from the 2500-ppm group as well as for male and female rats from
      the 5000-ppm group. At the interim euthanasia, a concentration-related increase
      in testes weight (absolute and relative as a percentage of body and brain weight)
      was observed for male rats. Concentration-related increases in absolute and
      relative liver weight (as a percentage of body weight) were observed for male and
      female mice. In addition, increased absolute and/or relative (as a percentage of
      body and brain weight) liver and kidney weights were observed for male and/or
      female rats from the 2500- and 5000-ppm groups. At necropsy, an increased
      incidence of seminal vesicle enlargement was observed grossly for male mice from
      the 2500- and 5000-ppm groups. Microscopically, some of the nonneoplastic lesions
      noted for mice included an increased incidence of ectasia of the seminal vesicles
      for male mice from the 2500- and 5000-ppm groups, minimal renal tubular
      proteinosis for male and female mice from all isopropanol groups, and renal
      tubular dilation for female mice from the 5000-ppm group. A number of
      nonneoplastic lesions were observed for male and female rats from the 2500- and
      5000-ppm groups, with the most significant lesions being observed in the kidney
      and associated with chronic renal disease. The lesions noted with increased
      severity and/or frequency included mineralization, tubular dilation,
      glomerulosclerosis, interstitial nephritis, interstitial fibrosis,
      hydronephrosis, and transitional cell hyperplasia. The only tumor type increased
      in incidence during the study was interstitial cell adenomas of the testes in
      male rats. However, the increase in these adenomas was not believed to be
      exposure-related due to an unusually low incidence observed for the control
      group. There were no increased frequencies of neoplastic lesions noted for male
      or female mice or for female rats from any isopropanol exposure group. Chronic
      renal disease was attributed to be the main cause of death for male and female
      rats from the 5000-ppm group and was also considered to account for much of the
      mortality observed for male rats from the 2500-ppm group. In conclusion, the no
      observed-effect level (NOEL) for toxic effects for both rats and mice was 500
      ppm. The NOEL for oncogenicity effects for both mice and rats was determined to
      be greater than 5000 ppm.

PMID- 9143480
TI  - Effects of lifetime lead exposure in monkeys on detection of pure tones.
AB  - Increased detection thresholds for pure tones were observed in a large cohort of
      children exposed to lead environmentally while smaller studies in lead-exposed
      workers have reported conflicting results on assessments of auditory function.
      Pure tone detection thresholds were determined in a group of monkeys (Macaca
      fascicularis) dosed with 2 mg/kg/day of lead from birth through testing at 13
      years of age. Blood lead concentrations were stable at about 30 micrograms/dl
      until monkeys were 10-11 years of age at which time they increased to between 50
      and 70 micrograms/dl. Five age- and rearing-matched monkeys served as controls.
      Detection thresholds were determined at six frequencies between 0.125 and 31.5
      kHz. Ear phones were fit over both ears, and thresholds were determined for each
      ear separately. The monkey signaled detection of the tone by breaking contact
      with a stainless steel bar. Three lead-exposed monkeys exhibited normal pure tone
      detection functions. Three monkeys had thresholds outside of the control range at
      some frequencies; there was a tendency for higher frequencies to be
      differentially more affected. These findings are consistent with reports of
      elevated pure tone thresholds in humans exposed to lead developmentally, although
      the effect is smaller than might have been predicted given the concurrent blood
      lead concentrations of these monkeys.

PMID- 9143481
TI  - Benzene-induced hematotoxicity and bone marrow compensation in B6C3F1 mice.
AB  - Long-term inhalation exposure of benzene has been shown to cause hematotoxicity
      and an increased incidence of acute myelogenous leukemia in humans. The
      progression of benzene-induced hematotoxicity and the features of the toxicity
      that may play a major role in the leukemogenesis are not known. We report the
      hematological consequences of benzene inhalation in B6C3F1 mice exposed to 1, 5,
      10, 100, and 200 ppm benzene for 6 hr/day, 5 days/week for 1, 2, 4, or 8 weeks
      and a recovery group. There were no significant effects on hematopoietic
      parameters from exposure to 10 ppm benzene or less. Exposure of mice to 100 and
      200 ppm benzene reduced the number of total bone marrow cells, progenitor cells,
      differentiating hematopoietic cells, and most blood parameters. Replication of
      primitive progenitor cells in the bone marrow was increased during the exposure
      period as a compensation for the cytotoxicity induced by 100 and 200 ppm benzene.
      In mice exposed to 200 ppm benzene, the primitive progenitor cells maintained an
      increased percentage of cells in S-phase through 25 days of recovery compared
      with controls. The increased replication of primitive progenitor cells in concert
      with the reported genotoxicity induced by benzene provides the components
      necessary for producing an increased incidence of lymphoma in mice. Furthermore,
      we propose this mode of action as a biologically plausible mechanism for benzene
      induced leukemia in humans exposed to high concentrations of benzene.

PMID- 9143482
TI  - Evaluation of a human corneal epithelial cell line as an in vitro model for
      assessing ocular irritation.
AB  - A human corneal epithelial cell line, 10.014 pRSV-T (HCR-T cells), has been used
      to develop a three-dimensional in vitro model of the human corneal epithelium
      (HCE-T model). HCE-T cells form a stratified culture when grown at the air-liquid
      interface on a collagen membrane in serum-free medium. This model served as the
      basis for assays which supported the ocular irritancy assessment of water-soluble
      test substances. Cellular alterations in the HCE-T model were measured following
      5-min topical exposures to 20 chemicals [listed in the European Center for
      Ecotoxicology and Toxicology of Chemicals (ECETOC) Reference Chemicals Data Bank]
      and 25 surfactant-based product formulations [utilized in the Cosmetic, Toiletry,
      and Fragrance Association (CTFA) Alternatives Program Phase III]. In vitro assays
      used were transepithelial permeability to sodium fluorescein (TEP) and
      transepithelial electrical resistance (TER). These measured alterations in the
      barrier function of this corneal epithelial equivalent. Barrier function is a
      well-developed property in the HCE-T model that supports the mechanistic
      relevance of these assays. In vitro data, averaged from replicate assays, were
      compared to respective Draize rabbit eye irritation data from the publicly
      available ECETOC and CTFA databases using linear regression with Pearson's
      correlation analysis. For chemicals, Pearson's correlation coefficients, r, from
      comparisons of Draize maximum average scores (MAS) to TEP and TER data were 0.71
      and 0.55, respectively. For product formulations, Pearson's correlation
      coefficients from comparisons of Draize MAS to TEP and TER data were 0.86 and
      0.80, respectively. Data indicated that barrier function alterations in the HCE-T
      model correlated with ocular irritancy and corneal toxicity. While the irritancy
      of the chemicals tested was effectively assessed only by the TEP assay, that for
      the surfactant-based product formulations was effectively assessed by both the
      TEP and TER assays. Results also suggested that the HCE-T TEP and TER assays vary
      in their effectiveness for evaluating specific classes of test materials.

PMID- 9143483
TI  - Biological markers of acute acrylonitrile intoxication in rats as a function of
      dose and time.
AB  - Three markers of acute acrylonitrile (AN) intoxication, namely, tissue
      glutathione (GSH), tissue cyanide (CN), and covalent binding to tissue protein,
      were studied as a function of dose and time. Doses administered and responses
      expected were 20 mg/kg (LD0), 50 mg/kg (LD10), 80 mg/kg (LD50), and 115 mg/kg
      (LD90). Liver GSH was the most sensitive marker of AN exposure. At 80 mg/kg AN,
      virtually complete depletion of liver GSH was observed within 30 min with no
      recovery through 120 min. Kidney GSH showed a similar, but less intense
      depletion; while blood and brain GSH were more refractory to AN. Whole blood and
      brain CN rose progressively during the first 60 min in a dose-dependent fashion.
      At the lowest dose, CN levels decreased thereafter, whereas, at the three higher
      doses, CN levels were maintained or continued to increase through 120 min. At the
      highest dose, blood and brain CN remained at acutely toxic levels through 240
      min. Covalent binding increased rapidly in all tissues during the first 30 min at
      all doses. At the lowest dose, little additional covalent binding was observed
      beyond 30 min, while at the three higher doses, covalent binding increased,
      although at a slower rate. The data indicate that these three biologic markers of
      acute AN intoxication respond dramatically in a time-dependent manner in the
      toxic dosage range. Furthermore, the data provide evidence that AN toxicity is
      gated by GSH depletion in liver with the resultant termination of AN
      detoxification.

PMID- 9143484
TI  - Dose dependence of covalent binding of acrylonitrile to tissue protein and globin
      in rats.
AB  - The dose dependence of acrylonitrile (AN) covalent binding to tissue protein,
      following a single acute exposure over a 100-fold range in dose, was measured.
      Covalent binding was a linear function of AN dose in the lower dose range (0.02
      0.95 mmol AN/kg). The slopes of the dose-response curves indicated that tissues
      varied by nearly 10-fold in their reactivity with AN. The relative order of
      covalent binding was as follows: blood > > kidney = liver > forestomach = brain >
      glandular stomach > > muscle. Similar dose-response behavior was observed for
      globin total covalent binding and for globin N-(2-cyanoethyl) valine (CEValine)
      adduct formation. The latter adduct was found to represent only 0.2% of the total
      AN adduction to globin. Regression of tissue protein binding versus globin total
      covalent binding or globin CEValine adduct indicated that both globin biomarkers
      could be used as surrogates to estimate the amount of AN bound to tissue protein.
      At higher AN doses, above approximately 1 mmol/kg, a sharp break in the covalent
      binding dose-response curve was observed. This knot value is explained by the
      nearly complete depletion of liver glutathione and the resultant termination of
      AN detoxification. The toxicity of AN is known to increase sharply above this
      dose. The data suggest that a comparison of specific tissue proteins labeled by
      AN above and below this threshold dose may provide some insight into the
      mechanism of AN-induced toxicity.

PMID- 9143485
TI  - Stimulation of prostaglandin production by quinolone phototoxicity in Balb/c 3T3
      mouse fibroblast cells in vitro.
AB  - Sparfloxacin (SPFX) and levofloxacin (LVFX) with ultraviolet-A (UVA) irradiation
      have been reported to induce skin inflammation due to phototoxicity in Balb/c
      mice. We examined the production of arachidonic acid metabolites induced by
      quinolone phototoxicity in Balb/c 3T3 mouse fibroblast cells in vitro. The cells
      were simultaneously treated with SPFX or LVFX at 1, 10, or 100 microM and UVA
      irradiation for 5 min (0.5 J/cm2). They were then cultured in quinolone-free
      medium for 24 hr, and the concentrations of prostaglandin E2 (PGE2), 6
      ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), and leukotriene B4 (LTB4) in the
      incubation medium were measured. Furthermore, the effect of quinolone
      photoproducts on the production of the inflammatory mediators and that of
      indomethacin on PGE2 level were also examined. Treatment with SPFX at 100 microM
      plus UVA irradiation markedly increased levels of PGE2 and 6-keto-PGF1 alpha, but
      not that of LTB4. SPFX or LVFX alone at up to 100 microM, 10 microM SPFX, or 100
      microM LVFX, or less plus UVA irradiation, or UVA-preirradiated quinolone up to
      100 microM had no effect. Indomethacin even at 0.1 microM completely inhibited
      the PGE2 elevation induced by 100 microM SPFX with UVA. These results suggest
      that PGs released from dermal fibroblasts in the simultaneous presence of
      quinolone and UVA could contribute in part to the development of skin
      inflammation in vivo.

PMID- 9143486
TI  - Perinatal methanol exposure in the rat. II. Behavioral effects in neonates and
      adults.
AB  - The use of methanol as a component of automobile fuel will increase perinatal
      exposures in the general population. Few studies have addressed questions
      concerning neurotoxicity stemming from such exposures. In the current study, four
      cohorts of pregnant Long-Evans rats, each cohort consisting of an exposure and a
      control group, were exposed to 4500 ppm methanol vapor in Rochester-type
      inhalation chambers for 6 hr daily beginning on Gestation Day 6. Exposure
      continued for both dams and pups through Postnatal Day 21 (PND 21) to model
      gestational and neonatal toxicity in humans. Several behavioral procedures were
      used to assess exposure effects in the offspring. Male-female littermates were
      studied whenever possible to examine sex differences, with one pair from a litter
      for each procedure. Exposure to methanol did not affect suckling latency and
      nipple attachment on PND 5 or performance on an aversive olfactory conditioning
      procedure on PND 10. Exposure to methanol did alter performances in a motor
      activity procedure. Methanol-exposed neonates were less active on PND 18, but
      more active on PND 25 than the equivalent control group pups. Two operant
      conditioning procedures, not used previously in this context, assayed other
      littermates as adults. A fixed ratio schedule required the rat to rotate a
      running wheel a specified number of revolutions to obtain food-pellet
      reinforcers. When the fixed ratio requirement changed, number of responses
      (revolutions) per 1-hr session displayed a complex interaction with treatment.
      Changes in performance over the course of training differed between males and
      females depending on exposure to methanol. Compared to initial baseline
      performances, methanol-exposed males showed decreases, and methanol-exposed
      females increases, in the rate of running. A stochastic spatial discrimination
      procedure permitted subjects to respond on any three levers, with the
      probabilities of food-pellet delivery determined by the location of the preceding
      response. A reinforcement matrix defined the response sequence required to
      maximize reinforcements. When the matrix was changed, the methanol-exposed
      subjects responded less efficiently at asymptotic levels of performance than
      controls. Across procedures, developmental exposure to 4500 ppm methanol vapor
      was associated with subtle behavioral changes in both neonates and adults.

PMID- 9143487
TI  - Bioavailability of lead to juvenile swine dosed with soil from the Smuggler
      Mountain NPL Site of Aspen, Colorado.
AB  - Bioavailability of lead (Pb) has become an issue in quantifying exposure of
      sensitive populations and, where necessary, establishing cleanup levels for
      contaminated soil. Immature swine were used as a model for young children to
      estimate the degree to which Pb from two fully characterized composite samples
      from the Smuggler Mountain Superfund Site in Aspen, Colorado may be bioavailable
      to resident children. The composite soils contained 14,200 and 3870 micrograms
      Pb/g of soil. Relative and absolute enteric bioavailabilities of Pb in soil (oral
      dose groups of 75,225, and 675 micrograms Pb/kg body wt/day) were estimated by
      comparison with an orally administered soluble Pb salt (lead acetate =
      PbAc2.3H2O) (dose groups of 0, 75, and 225 micrograms Pb/kg body wt/day) and an
      intravenously administered aqueous solution of Pb (100 micrograms Pb/kg/ day)
      from the same trihydrate salt administered daily for 15 days to 50 juvenile
      swine. The biological responses (area under the blood Pb concentration-time
      curve, and the terminal liver-, kidney-, and bone-lead concentrations) produced
      by Pb from PbAc2.3H2O and lead-contaminated soils were determined. This study
      revealed Pb from soil containing 14,200 micrograms Pb/g of soil had a
      bioavailability relative to Pb from PbAc (RBA), ranging from 56% based on the
      area under the blood lead concentration-time curve (AUC) versus dose, to 86%
      based on calculations from liver-Pb loading versus dose. Similarly, Pb from soil
      containing 3870 micrograms Pb/g of soil had an RBA ranging from 58% based on the
      AUC versus dose, to 74% based on calculations from liver- and kidney-Pb loading
      versus dose. Bioavailability of Pb in soils may be more or less than EPA's
      default RBA of 60%, therefore, measuring site-specific RBAs provides a basis for
      improved exposure and risk assessment.

PMID- 9143488
TI  - Binning clones by hybridization with complex probes: statistical refinement of an
      inner product mapping method.
AB  - Molecular methods that use long-range information to solve genomics problems
      (i.e., top-down strategies) efficiently have become increasingly prominent in the
      genomics literature. One such method, an implementation of inner product mapping
      (IPM), uses noisy, long-range radiation hybrid (RH)/YAC overlap data and
      relatively noise-free RH/STS overlap data to localize clones to specific
      chromosomal regions. Because the molecular data are rarely noise-free,
      statistical models tailored to the top-down molecular methods make the methods
      far more effective. We develop two statistical models for IPM (or any other top
      down strategy of similar form), a parametric logit model and a nonparametric
      order-restricted model, and show how these models can be implemented within a
      hierarchical Bayes framework. Using these models, we refine the chromosome 11 map
      reported in M. Perlin et al. (1995, Genomics 28: 315-327). Our analyses improve
      the IPM map, both in terms of successful localization of clones and in terms of
      the confidence with which they are localized.

PMID- 9143489
TI  - Genomic organization and chromosomal mapping of the murine alpha 1,2-mannosidase
      IB involved in N-glycan maturation.
AB  - alpha 1,2-Mannosidases are a family of enzymes with similar amino acid sequences
      that are required for the formation of complex and hybrid N-linked
      oligosaccharides in mammalian cells. We are reporting the first genomic structure
      of a member of this enzyme family, the murine alpha 1,2-mannosidase IB gene. Two
      BALB/c cosmid genomic clones (Cos.31.1 and Cos.25.1) and three overlapping 129/su
      P1 genomic clones were isolated. Analysis of Cos.31.1 and the P1 clones showed
      that the alpha 1,2-mannosidase IB gene spans > or = 80 kb of the genome and
      consists of 13 exons representing the complete open reading frame of the enzyme.
      Fluorescence in situ hybridization with alpha 1,2-mannosidase IB genomic DNA
      (Cos.31.1) localized the gene to mouse chromosome 3F2. Sequence analysis of the
      Cos.25.1 cosmid clone provided evidence for the existence of another related gene
      or pseudogene. Fluorescence in situ hybridization with Cos.25.1 localized this
      sequence to mouse chromosome 4A13.

PMID- 9143490
TI  - Chromosomal mapping of five highly conserved murine homologues of the Drosophila
      RING finger gene seven-in-absentia.
AB  - Seven-in-absentia (sina) is epistatic to all other known genes in the sevenless
      ras signaling pathway, which mediates R7 photoreceptor formation in the
      Drosophila eye. The murine genome contains several closely related sina
      homologues (Siah1A-D, Siah2) that are also likely to participate in ras
      signaling. As part of a genetic and biochemical analysis of the mammalian Siah
      genes, we have used gene-specific probes to map the chromosomal positions of each
      family member. Here we report their chromosomal positions in relation to a number
      of known mouse mutations and also describe an analysis of the human Siah genes.
      By comparing the complexity of the Siah genes in these two mammalian species we
      have gained further insight into which members of this murine multigene family
      are likely to be functional.

PMID- 9143491
TI  - Genomic organization and chromosome localization of the human cathepsin K gene
      (CTSK).
AB  - Human cathepsin K is a recently described cysteine protease with high sequence
      homology to cathepsins S and L, members of the papain superfamily of cysteine
      proteases. Cathepsin K is abundantly and selectively expressed in osteoclasts and
      may perform a specialized role in osteoclast-mediated bone resorption. In the
      present study, the genomic organization and chromosomal localization of human
      cathepsin K (HGMW-approved symbol CTSK) were determined. Intron-exon boundaries
      were identified by PCR on human genomic DNA, and subsequently a P1 genomic clone
      containing the full-length gene was isolated. Cathepsin K spans approximately
      12.1 kb of genomic DNA and is composed of eight exons and seven introns. The
      genomic organization of cathepsin K is similar to that of cathepsins S and L. The
      gene was mapped to chromosome 1q21 by fluorescence in situ hybridization. Primer
      walking on the P1 genomic clone identified 1108 bp of 5' flanking sequence and
      459 bp of 3' flanking sequence. Ribonuclease protection assay and 5' RACE
      indicated a single transcriptional start site 49 bp upstream of the initiator Met
      codon. Analysis of the 5' flanking region indicates that this gene lacks
      canonical TATA and CAAT boxes and contains multiple potential transcription
      regulatory sites. The characterization of the cathepsin K gene and its promoter
      may provide valuable insights not only into its osteoclast-selective expression,
      but also into the molecular mechanisms responsible for osteoclast activation.

PMID- 9143492
TI  - Tetraodon fluviatilis, a new puffer fish model for genome studies.
AB  - The puffer fish Fugu rubripes rubripes was recently introduced by S. Brenner et
      al. (1993, Nature 366: 265-268) as a new model for genomic studies. Due to
      difficulties in obtaining material from this Japanese marine puffer, we have
      started work on Tetraodon fluviatilis, a small, freshwater puffer fish that can
      be kept and bred in an aquarium. It was originally described by E. Hinegardner
      (1968, Am. Nat. 102(928) 517-523) as the teleost with the smallest amount of DNA
      per cell (0.4 pg, 380 Mb). To estimate the extent of divergence between T.
      fluviatilis and F. r. rubripes, part of the mitochondrial cytochrome b (cyt b)
      gene from both fishes was cloned and sequenced. A comparison of these two
      sequences indicated that F.r. rubripes and T. fluviatilis diverged approximately
      18-30 million years ago, and phylogenetic analysis placed both fishes at the base
      of the Perciformes lineage. To facilitate and extend further the use of the
      puffer fish as a model for genome studies, we have constructed and characterized
      a T. fluviatilis cDNA library.

PMID- 9143493
TI  - A sequence-ready high-resolution physical map of the best macular dystrophy gene
      region in 11q12-q13.
AB  - Best disease, an autosomal dominant inherited macular degenerative disorder, was
      previously localized between D11S1765 and UGB (uteroglobin) in 11q13 by genetic
      linkage analysis. Since this region was found to be refractory to cloning in YAC
      (yeast artificial chromosome)-based vectors, a P1 artificial chromosome (PAC)
      contig was assembled. Gridded PAC libraries representing a 16-fold genome
      equivalent were screened by hybridization using PCR products representing STSs
      derived from YAC end sequences, markers binned to 11q13, and PAC-derived insert
      ends. A highly marker dense approximately 1.7-Mb PAC contig that encompassed the
      disease gene region was constructed, allowing us to order accurately the markers
      throughout the region and to provide the most precise estimate of its physical
      size. Using this contig, thus far we have mapped seven anonymous ESTs and five
      known genes into this region. This high-resolution physical map will facilitate
      the isolation of polymorphic markers for refinement of the disease gene region,
      as well as the identification of candidate genes by exon trapping, cDNA
      selection, and gene prediction from PAC-derived genomic sequence.

PMID- 9143494
TI  - Cloning of a novel homeobox-containing gene, PKNOX1, and mapping to human
      chromosome 21q22.3.
AB  - To contribute to the development of the transcript map of human chromosome 21 and
      to the understanding of the pathogenesis of Down syndrome, we have used exon
      trapping to identify portions of genes from pools of HC21-specific cosmids. More
      than 550 potential exons have been isolated to date. One such trapped exon,
      hmc37a09 (GenBank Accession No. X88106), was identical to a region of a human
      EST, L12425 (GenBank Accession No. D31072). Its predicted amino acid sequence was
      homologous to the homeodomain region of homeobox-containing genes. Using the
      trapped sequence and the EST as probes to screen human fetal brain and kidney
      cDNA libraries, we have cloned the corresponding full-length cDNA. This novel
      gene encodes a homeodomain-containing polypeptide of 436 amino acids. The most
      closely related sequence is that of the mouse Meis1, a PBX-like homeobox gene.
      The homeodomain of the novel gene is closely related to those of the mammalian
      PBX family and the plant Knotted1 family (involved in plant development). This
      gene is named PKNOX1 by the Human Nomenclature Committee. By PCR amplification,
      hybridization, and genetic linkage analysis using a (GT)n polymorphism in the
      3'UTR, we have precisely localized PKNOX1 to chromosome 21q22.3 between markers
      D21S212 and D21S25 on YAC350F7. PKNOX1 is expressed in many human tissues tested
      by Northern blot analysis. The involvement of the PKNOX1 gene in Down syndrome
      and/or monogenic disorders associated with dysfunction of this gene is presently
      unknown. Targeted disruption of the PKNOX1 homolog in mice will enhance our
      understanding of its biological function in normal mammalian development.

PMID- 9143495
TI  - Cloning and characterization of a mouse sensory neuron tetrodotoxin-resistant
      voltage-gated sodium channel gene, Scn10a.
AB  - Small-diameter sensory neurons associated with unmyelinated axons express a
      tetrodotoxin-insensitive (TTXi) voltage-gated sodium channel (VGSC) that may play
      an important role in the transmission of nociceptive information to the spinal
      cord. A TTXi VGSC, named SNS, that accounts for the tetrodotoxin-resistant sodium
      current described in sensory neurons has been cloned from rat dorsal root
      ganglia. Using recombinant lambda phage clones encoding a mouse 129/SV genomic
      library, we have determined the detailed structure of the mouse SNS gene
      (Scn10a), including the location of exon-intron boundaries and the nucleotide
      sequence of the exons. The gene consists of 27 exons spanning approximately 90 kb
      on chromosome 9. Mouse SNS shows 95.3% overall amino acid identity to rat SNS and
      98.5% identity throughout the putative transmembrane segments and the
      intracellular loop linking domains 3 and 4. The sizes of the exons and the exon
      intron junction positions of the mouse SNS and the human skeletal muscle VGSC
      genes are remarkably conserved. These results provide the basis for an
      evolutionary comparison of sodium channels, the construction and analysis of a
      mouse SNS null mutant as a direct approach to understanding the biological
      function of SNS, and the identification of regulatory elements that are
      responsible for the tissue- and cell-specific expression of SNS.

PMID- 9143496
TI  - Cloning of a human RNA editing deaminase (ADARB1) of glutamate receptors that
      maps to chromosome 21q22.3.
AB  - RED1 is a double-stranded RNA-specific editase characterized in the rat and is
      implicated in the editing of glutamate receptor subunit pre-mRNAs, particularly
      in the brain. Starting from human ESTs homologous to the rat RED1 sequence, we
      have characterized two forms of human RED1 cDNAs, one form coding for a putative
      peptide of 701 amino acids (similar to the shorter of two rat mRNAs) and a long
      form coding for a putative protein of 741 amino acids, the extra 120 bp of which
      are homologous to an AluJ sequence. Both forms were observed at approximately
      equal levels in cDNA clones and in seven different human tissues tested by RT
      PCR. The human and rat short isoforms have 95 and 85% sequence identity at the
      amino acid and nucleotide levels, respectively. The human sequence (designated
      ADARB1 by the HGMW Nomenclature Committee) contains two double-stranded RNA
      binding domains and a deaminase domain implicated in its editing action. Northern
      blot analysis detected two transcripts of 8.8 and 4.2 kb strongly expressed in
      brain and in many human adult and fetal tissues. ADARB1 maps to human chromosome
      21q22.3, a region to which several genetic disorders map, including one form of
      bipolar affective disorder. Recently it was shown that heterozygous mice
      harboring an editing-incompetent glutamate receptor B allele have early onset
      fatal epilepsy. Since glutamate receptor channels are essential elements in
      synaptic function and plasticity and mediate pathology in many neurological
      disorders, and since RED1 is central in glutamate receptor channel control,
      ADARB1 is a candidate gene for diseases with neurological symptoms, such as
      bipolar affective disorder and epilepsy.

PMID- 9143497
TI  - BAC and PAC contigs covering 3.5 Mb of the Down syndrome congenital heart disease
      region between D21S55 and MX1 on chromosome 21.
AB  - Chromosome 21 is a model for the study of human chromosomal aneuploidy, and the
      construction of its physical and transcriptional maps is a necessary step in
      understanding the molecular basis of aneuploidy-dependent phenotypes. To identify
      the gene(s) responsible for Down syndrome congenital heart disease (DS-CHD), we
      constructed a physical map of the D21S55 to MX1 region. A bacterial artificial
      chromosome (BAC) library was screened using several YACs spanning the interval,
      and a P1-derived artificial chromosome (PAC) library was screened using
      radiolabeled STS PCR products and whole BACs in gap-filling initiatives. FISH
      confirmed the location of all BAC and PAC clones to 21q22.2-q22.3. Overlaps were
      established using clone-to-clone Southerns and 24 new STSs, generated from the
      direct sequencing of BAC and PAC ends, along with 35 preexisting STSs.
      Approximately 3.5 Mb of the 4- to 5-Mb D21S55 to MX1 interval is covered in 85
      BACs and 24 PACs, representing fourfold coverage within the contigs. These BAC
      and PAC contigs are valuable reagents for isolating the genes for DS-CHD.

PMID- 9143498
TI  - Gene sequence, localization, and evolutionary conservation of DAZLA, a candidate
      male sterility gene.
AB  - We have isolated the human homologue of the mouse germ cell-specific transcript
      Tpx2, which we had previously mapped to mouse chromosome 17. Sequence analysis
      shows that the human gene is part of the DAZ (Deleted in Azoospermia) family,
      represents the human homologue of the mouse Dazla and Drosophila boule genes, and
      is termed DAZLA. Like Dazla and boule, DAZLA is single copy and maps to 3p25.
      This defines a new region of synteny between mouse chromosome 17 and human
      chromosome 3. Unlike DAZ, which has multiple DAZ repeats, DAZLA encodes a
      putative RNA-binding protein with a single RNA-binding motif and a single DAZ
      repeat. DAZLA is more closely related to Dazla in the mouse than to the Y-linked
      homologue DAZ (88% identity overall with mouse Dazla compared to 76% identity
      with the human DAZ protein sequence). Southern blot analysis showed that DAZLA is
      autosomal in all mammals tested and that DAZ has been recently translocated to
      the Y chromosome, sometime after the divergence of Old World and New World
      primates. To investigate the evolutionary relatedness of DAZLA and DAZ further,
      their partial genomic structures were obtained and compared. This revealed that
      the genomic organization of both genes in the 5' region is highly conserved.
      DAZLA is a new member of the DAZ family of genes, which is associated with
      spermatogenesis and male sterility. Familial cases of male infertility in humans
      show an autosomal recessive mode of inheritance. It is possible that some of
      these families may carry mutations in the DAZLA gene.

PMID- 9143499
TI  - Complete primary structure of two splice variants of collagen XII, and assignment
      of alpha 1(XII) collagen (COL12A1), alpha 1(IX) collagen (COL9A1), and alpha
      1(XIX) collagen (COL19A1) to human chromosome 6q12-q13.
AB  - Overlapping cDNA clones that encode the full-length human alpha 1(XII) collagen
      polypeptides were isolated. The long variant molecule cDNA of 9750 nucleotides
      (nt) contains a 9189-nt open reading frame encoding 3063 amino acid residues. The
      short variant molecule cDNA of 6258 nt contains a 5697-nt open reading frame
      encoding 1899 amino acid residues. At the amino terminus of each variant is a 24
      residue signal peptide that is followed by the mature polypeptides of 3039 amino
      acid residues with a calculated molecular mass of 330,759 Da for the long variant
      and 1875 amino acid residues with a calculated molecular mass of 203,163 Da for
      the short variant polypeptide. The human collagen XII chains are predicted to
      have all the structural domains described for the molecules in chicken and mouse,
      including, fibronectin type III repeats, von Willebrand factor A domains, and two
      triple-helical domains similar to those of all the other collagen family members.
      The amino acid residue sequence of human alpha 1(XII) collagen showed 92%
      identity to the mouse chain and 78% identity to the chicken chain. The sequence
      of three peptide fragments of collagen XII isolated from human placenta was
      identical to the sequence predicted from the deduced cDNA sequence and confirms
      that the cDNA encodes human alpha 1(XII) collagen. An isolated genomic clone was
      used to map the locus of the COL12A1 gene to chromosome 6q12-q13, very close to
      the locus of the FACIT collagen genes COL9A1 and COL19A1. RT-PCR on a variety of
      cDNAs demonstrates that both variant transcripts appear in human amnion, chorion,
      skeletal muscle, small intestine, and in cell cultures of human dermal
      fibroblasts, keratinocytes, and endothelial cells. Only the small variant
      transcript is apparent in human lung, placenta, kidney, and a squamous cell
      carcinoma cell line. These results confirm the previous observations showing that
      collagen XII is found in collagen I-containing tissues.

PMID- 9143500
TI  - Structure, organization, and chromosomal mapping of the human neurogranin gene
      (NRGN).
AB  - In this report the identification, structure, and chromosomal localization of the
      human neurogranin gene (NRGN) are described. NRGN is the human homolog of the rat
      Ng/RC3 gene, which encodes a brain-specific protein expressed in telencephalic
      neurons. The human NRGN gene spans approximately 12 kb and contains four exons
      and three introns. All splice acceptor and donor sites conform to the canonical
      AG/GT rule. Human neurogranin sequence predicts a 78-amino-acid protein with 5
      amino acids encoded by exon 1 and the remaining 73 amino acids encoded by exon 2.
      The third and fourth exons contain untranslated sequences. The overall degree of
      homology between the human and the rat coding sequences is 90% for the nucleic
      acid sequence, with 96% identity and 97.5% similarity at the protein level. The
      NRGN gene is expressed exclusively in brain as a single 1.3-kb mature mRNA. The
      promoter lacks both TATA and CAAT boxes, but shows a consensus sequence for an
      initiator element located 234 bases upstream from the AUG initiation codon. The
      5'-flanking region contains multiple putative binding sites for transcription
      factors such as Sp1, GCF, AP2, and PEA3. Analysis of a panel of radiation hybrids
      has led to localization of the NRGN gene in YAC 763A2 (CEPH), previously mapped
      at 11q24. This locus is contained in a region of conserved synteny with mouse
      chromosome 9.

PMID- 9143501
TI  - Organization, sequence, chromosomal localization, and promoter identification of
      the mouse orphan nuclear receptor Nurr1 gene.
AB  - We have cloned and characterized the organization of the mouse orphan nuclear
      receptor Nurr1 gene. The Nurr1 gene is approximately 7 kb long, contains eight
      exons and seven introns, and mapped to mouse chromosome 2. Although the
      exon/intron structure of Nurr1 is nearly identical to that of Nur77, Nurr1
      possesses an additional untranslated exon. Primer extension was used to identify
      two major transcription initiation sites mapped 37 nucleotides apart in the first
      untranslated exon. Functional studies of chimeric Nurr1-luciferase reporter genes
      delineated the promoter region and underscored the importance of the +1
      transcription start site. Sequence analysis of the 5' flanking region surrounding
      +1 revealed several possible response elements such as a hexanucleotide
      glucocorticoid binding site, a cAMP-response element, a CArG box, and two c-Jun
      binding sites. These data help to explain the different response characteristics
      of two closely related early response genes, Nurr1 and Nur77.

PMID- 9143503
TI  - The human E6-AP gene (UBE3A) encodes three potential protein isoforms generated
      by differential splicing.
AB  - The E6-AP gene (UBE3A) encodes an E3 ubiquitin-protein ligase that binds the
      human papillomavirus E6 oncoprotein and catalyzes the ubiquitination of p53.
      Recent studies have also established that mutations in E6-AP are the genetic
      basis of the Angelman syndrome in humans. In this study we present the genomic
      structure of the coding region of E6-AP and an analysis of a set of five E6-AP
      mRNAs with the potential to encode three protein isoforms of the E6-AP protein
      (isoforms I, II, and III) that differ at their extreme amino-termini. These
      transcripts were expressed in a variety of different cell lines examined.

PMID- 9143502
TI  - Structure and chromosomal assignment of the human cathepsin K gene.
AB  - Cathepsin K is a recently identified lysosomal cysteine proteinase that is the
      major protease responsible for bone resorption and remodeling. Mutations in this
      gene cause the sclerosing osteochondrodysplasia pycnodysostosis. To assess its
      evolutionary relatedness to other cysteine proteases and to facilitate mutation
      identification in patients with pycnodysostosis, a genomic clone, 74e16,
      containing the cathepsin K gene was isolated from a human PAC library, and the
      cathepsin K genomic structure was determined. The cathepsin K gene contained
      eight exons and spanned approximately 9 kb. The transcription initiation site,
      determined by primer extension analysis, was 169 nucleotides upstream from the
      translation initiation site. The 5'-flanking region lacked a TATA box but
      contained two AP1 sites. Comparison of genomic and cDNA sequences suggested that
      this flanking sequence may be the major promoter in osteoclasts and macrophages.
      Cathepsin K was mapped to chromosome 1q21 by fluorescence in situ hybridization
      and found to reside within 150 kb of an evolutionarily related cysteine protease,
      cathepsin S. These findings expand our understanding of the papain family
      lysosomal cysteine proteases and should facilitate mutation analysis in
      pycnodysostosis.

PMID- 9143505
TI  - Deletions of distal 9p associated with 46,XY male to female sex reversal:
      definition of the breakpoints at 9p23.3-p24.1.
AB  - Monosomy of distal 9p is associated in rare cases with abnormalities of
      testicular determination, which can lead to male to female sex reversal in a
      46,XY genetic background. We present two 46,XY individuals partially monosomic
      for 9p who were raised as females. Definition of the breakpoints using somatic
      cell hybrids containing only the rearranged chromosome 9 indicated that in the
      first patient the breakpoint was located between markers D9S256 and D9S144 and in
      the second patient, the breakpoint was distal to the marker D9S144. In both cases
      this corresponds to the cytogenetic position 9p23.3-p24.1. Analysis of highly
      polymorphic microsatellite markers demonstrated a paternal origin of the
      rearranged chromosome 9 in both patients. These studies define the minimum region
      associated with male to female sex reversal as 9p24.1-pter.

PMID- 9143504
TI  - Cloning and chromosomal localization of mouse aquaporin 4: exclusion of a
      candidate mutant phenotype, ataxia.
AB  - Aquaporin-4 is a mammalian water channel protein that is predominately expressed
      in brain, where it is believed to mediate water homeostasis. Here we report the
      isolation and characterization of the cDNA for mouse Aqp4 and map the gene to the
      proximal region of mouse chromosome 18. This region contains the neurological
      mutation ataxia, but further analysis reveals that Aqp4 is not responsible for
      the ataxia phenotype.

PMID- 9143506
TI  - Isolation and chromosomal mapping of a novel ATP-binding cassette transporter
      conserved in mouse and human.
AB  - We report here on the identification and genomic mapping of a novel member of the
      family of the ATP-binding cassette (ABC) transporters, ABC7, conserved in mouse
      and in humans. The ABC7 gene encodes a protein with the typical features of half
      transporters, such as those involved in translocation of antigenic peptides or in
      peroxisomal disorders. ABC7 shows a ubiquitous expression pattern and maps to the
      X chromosome both in mouse and in humans. The high sequence similarity to those
      of two yeast half-transporters supports once again the extreme evolutionary
      conservation of this family of proteins.

PMID- 9143507
TI  - The NTN2L gene encoding a novel human netrin maps to the autosomal dominant
      polycystic kidney disease region on chromosome 16p13.3.
AB  - The netrins define a family of chemotropic factors that have been shown to play a
      central role in axon guidance. We identified two exon traps encoding netrin-like
      sequences during the assembly of a transcriptional map for the genomic interval
      surrounding the polycystic kidney disease type 1 and tuberous sclerosis type 2
      genes. We describe the characterization of a novel human netrin-2-like gene,
      designated NTN2L, and its transcript. The genomic interval containing the NTN2L
      gene was sequenced, and the coding region was predicted based on computer
      analysis. The structure of the NTN2L gene has been confirmed utilizing nested RT
      PCR. The NTN2L gene is predicted to encode a 580-amino-acid protein having
      homology to the chicken and Drosophila netrins and to Caenorhabditis elegans UNC
      6. The NTN2L gene has a restricted pattern of expression; its transcript is
      undetectable by Northern analysis in all tissues examined, but can be recovered
      from spinal cord RNA by RT-PCR. This report represents the first description and
      characterization of a human netrin.

PMID- 9143508
TI  - Localization of the human Ror1 gene (NTRKR1) to chromosome 1p31-p32 by
      fluorescence in situ hybridization and somatic cell hybrid analysis.
AB  - Ror1 is an orphan cell surface receptor with strong homology to the tyrosine
      kinase domain of growth factor receptors, in particular the Trk family. Southern
      blot analysis of genomic DNA from somatic cell hybrids revealed that Ror1 is
      located on chromosome 1. We have mapped the Ror1 gene to chromosome 1p12-p32
      using PCR on a somatic cell hybrid panel that subdivides chromosome 1p. We have
      further localized the gene to chromosome 1p31-p32 by fluorescence in situ
      hybridization using a PAC clone that contains the Ror1 gene.

PMID- 9143509
TI  - Assignment of the dynamin-1 gene (DNM1) to human chromosome 9q34 by fluorescence
      in situ hybridization and somatic cell hybrid analysis.
AB  - The dynamins are recently discovered GTP-binding proteins postulated to mediate
      the scission of clathrin-coated vesicles at the plasma membrane. Of the three
      known mammalian dynamins, dynamin-1 (DNM1) appears to be particularly important
      for the formation of synaptic vesicles at presynaptic nerve termini. To
      investigate the possibility that mutations in the DNM1 gene cause a human
      disease, we determined the chromosomal localization of human DNM1. We conclude
      from fluorescence in situ hybridization and from the analysis of somatic cell
      hybrids that the map position in 9q34. This region has syntenic homology with
      mouse chromosome 2p, in agreement with the map position of the mouse DNM1 gene
      [see accompanying article by Klocke et al. (1997, Genomics 41:290-292)]. We
      discuss the potential relevance of the human DNM1 localization to diseases that
      were mapped genetically to the same chromosomal region.

PMID- 9143510
TI  - Dynamin genes Dnm1 and Dnm2 are located on proximal mouse chromosomes 2 and 9,
      respectively.
AB  - Dynamins, microtubule-binding GTPases, are encoded by at least three genes in
      mammals. Two distinct gene-specific cDNAs were used to analyze the segregation of
      dynamin genes Dnm1 and Dnm2 in a mouse interspecies backcross. The nervous system
      expressed gene Dnm1 was localized to Chr 2 between the genes for vimentin and
      nebulin, within a chromosomal region of conserved synteny to human chromosome 9q,
      consistent with the localization of the human dynamin-1 gene by FISH (see
      accompanying paper by Newman-Smith et al., 1997, Genomics 41:286-289). The
      ubiquitously expressed Dnm2 gene was found to be closely linked to the
      intercellular adhesion molecule-1 gene, Icam1, in a region with homologies to
      human chromosomes 19p, 8q, and 11q. Potential relations of both loci to disease
      genes are discussed.

PMID- 9143511
TI  - Mapping of the gene for the mouse telomerase RNA component, Terc, to chromosome 3
      by fluorescence in situ hybridization and mouse chromosome painting.

PMID- 9143512
TI  - The beta-chemokine receptor genes CCR1 (CMKBR1), CCR2 (CMKBR2), and CCR3 (CMKBR3)
      cluster within 285 kb on human chromosome 3p21.

PMID- 9143513
TI  - Localization of the novel serine/threonine protein phosphatase 6 gene (PPP6C) to
      human chromosome Xq22.3.

PMID- 9143514
TI  - The gene encoding the Schwann cell protein periaxin localizes on mouse chromosome
      7 (Prx).

PMID- 9143515
TI  - Cloning of a mouse homologue of the human Werner syndrome gene and assignment to
      8A4 by fluorescence in situ hybridization.

PMID- 9143516
TI  - Clone sheds light on research, ethical questions.

PMID- 9143518
TI  - VFD simplified.

PMID- 9143517
TI  - Stricter infectious substance regulations to be proposed.

PMID- 9143519
TI  - Another consideration for radiographic diagnosis.

PMID- 9143520
TI  - In favor of the metric system.

PMID- 9143521
TI  - Additional opinions on the morality of animal research.

PMID- 9143522
TI  - Additional opinions on the mortality of animal research.

PMID- 9143523
TI  - Additional opinions on the mortality of animal research.

PMID- 9143525
TI  - Additional opinions on the morality of animal research.

PMID- 9143526
TI  - Additional opinions on the mortality of animal research.

PMID- 9143524
TI  - Additional opinions on the mortality of animal research.

PMID- 9143527
TI  - Reshaping the veterinary medical profession for the next century.

PMID- 9143528
TI  - What is your diagnosis? Avulsion fracture of the calcaneus at the attachment of
      the long lateral collateral ligament of the tarsus.

PMID- 9143529
TI  - Arterial blood pressure monitoring in anesthetized animals.

PMID- 9143530
TI  - Some equine malpractice and liability cases.

PMID- 9143531
TI  - Residue avoidance after topical application of veterinary drugs and
      parasiticides.
AB  - Deriving adequate withdrawal intervals for extralabel use of veterinary topical
      products is difficult because there are limited published data, and data for
      approved drugs and pesticides are usually proprietary. Where possible, approved
      products and doses labeled for the specific indication at hand should be used and
      label withdrawal times should be adhered to. When determining whether topical
      application of these chemicals may violate tolerance levels in meat and milk, the
      veterinarian often is limited to empirical data. In the decision-making process,
      factors, such as type of drug and pesticide formulations used, method of topical
      application, presence of hair or wool, environmental conditions, and animal
      species treated, should be considered. In many cases a conservative estimate for
      the slaughter withdrawal interval can be derived, despite the data gaps. Such
      recommendations should not be used for routine extralabel use, but are meant to
      apply to situations in which the drug or pesticide has been used, and human food
      safety concerns must be addressed.

PMID- 9143532
TI  - Synovial fluid cavitation during distraction radiography of the coxofemoral joint
      in dogs.
AB  - OBJECTIVE: To determine risk factors for, and prevalence and short- and long-term
      effects of synovial fluid cavitation during distraction radiography. DESIGN:
      Multicenter prevalence survey. ANIMALS: 6,649 purebred dogs comprising 129
      breeds. PROCEDURE: Radiographs from the PennHIP (University of Pennsylvania Hip
      Improvement Program) Laboratory were subjectively evaluated for evidence of
      cavitation. Multiple logistic regression was used to determine whether sex,
      breed, age, weight, distraction index (DI), or examining veterinarian was
      associated with cavitation. Short-term effects of cavitation were assessed by
      comparing DI for the hip with cavitation with DI for the contralateral hip in
      dogs with unilateral cavitation. Long-term effects of cavitation were assessed by
      comparing DI before and after cavitation was detected. RESULTS: Cavitation was
      detected in 279 (4.2%) of the radiographs analyzed. Male dogs, Golden Retrievers,
      and heavier dogs were at a decreased risk for cavitation. Irish Wolfhounds, Irish
      Setters, Rhodesian Ridgebacks, and Weimaraners had an increased risk for
      cavitation. Age and DI were not risk factors for cavitation. Mean DI was 0.08
      greater in hips with cavitation than in paired hips without cavitation.
      Significant differences were not detected between DI before and after cavitation,
      but only 7 dogs were included in this analysis. CLINICAL IMPLICATIONS: Cavitation
      is rare during distraction radiography and can increase measured DI. Radiographs
      should be routinely examined to ensure accurate reporting of DI.

PMID- 9143533
TI  - Nimodipine for treatment of idiopathic epilepsy in dogs.
AB  - OBJECTIVE: To evaluate efficacy and safety of the calcium channel antagonist
      nimodipine in dogs with idiopathic epilepsy. DESIGN: Prospective clinical trial.
      ANIMALS: 10 dogs with idiopathic epilepsy. Dogs were included if seizures were
      inadequately controlled despite treatment with barbiturates and serum
      phenobarbital concentrations were > 25 micrograms/ml, if dogs had intolerable
      adverse effects when treated with barbiturates, or if dogs had mild, inadequately
      treated seizures. PROCEDURES: Dogs were treated with nimodipine (2.5 mg/kg [1.1
      mg/lb] of body weight, PO, q 12 h), and other medications were slowly withdrawn.
      Dogs were monitored for seizure frequency and severity as well as any adverse
      effects to the medication. RESULTS: Few adverse effects were reported. Seizure
      control, however, was generally inadequate. All but 2 dogs were withdrawn from
      the study because of poor seizure control. Plasma nimodipine concentrations were
      low, with a mean peak concentration of 105.3 ng/ml. CLINICAL IMPLICATIONS:
      Nimodipine was not successful in controlling seizures in dogs used in this study.

PMID- 9143534
TI  - Epidemiologic evaluation of postoperative wound infections in dogs and cats.
AB  - OBJECTIVE: To determine postoperative wound infection rates in dogs and cats for
      various wound contamination categories and to identify factors that influence
      postoperative wound infection rates. DESIGN: Epidemiologic study. SAMPLE
      POPULATION: 1,574 wounds in 1,255 dogs and cats. PROCEDURE: Information recorded
      included signalment, nutritional status, surgery duration, surgical procedures,
      wound contamination classification, interval from clipping until surgery, blood
      pressure values, active infection at a distant site, endocrinopathy, and
      administration of immunosuppressive medications or antibiotics. Relative risk,
      95% confidence intervals, and multiple regression analyses were performed.
      RESULTS: Postoperative infection was evident in 86 of 1,574 (5.5%) wounds,
      including 54 of 1,146(4.7%) and 13 of 259 (5.0%) animals with clean and clean
      contaminated wounds respectively, and 12 of 100 (12.0%) and 7 of 69 (10.1%)
      animals with contaminated and dirty wounds, respectively. Animals with clean
      wounds that received antibiotics other than as prescribed in our perioperative
      protocol had a higher infection rate than animals that did not receive
      antibiotics. Surgical sites clipped before anesthetic induction were 3 times more
      likely to become infected than sites clipped after induction. Risk of wound
      infection increased with increasing duration of surgery. CLINICAL IMPLICATIONS:
      Wound contamination categories had too much variation to make them useful for
      predicting animals that would develop wound infections. Surgical sites should be
      clipped immediately prior to surgery, and intraoperative time should be kept to a
      minimum. Unless indicated for other current active infection, prolonged use of
      antibiotics after surgery should be avoided in animals with clean wounds.

PMID- 9143535
TI  - Patterns of feline coronavirus infection and fecal shedding from cats in multiple
      cat environments.
AB  - OBJECTIVE: To determine, by use of a reverse transcriptase-polymerase chain
      reaction (RT-PCR) test, patterns of fecal shedding of feline coronavirus among
      cats. DESIGN: Prospective observational study. ANIMALS: 275 purebred cats from 6
      private catteries and 40 specific-pathogen-free (SPF) laboratory-reared cats.
      PROCEDURE: 40 SPF cats were experimentally inoculated with crude fecal extract
      containing feline enteric coronavirus (FECV). Fecal and plasma samples were
      collected every 4 days and evaluated by use of RT-PCR and indirect
      immunofluorescence assays, respectively, to correlate RT-PCR results with fecal
      infectivity and to determine patterns of FECV shedding and anti-FECV IgG
      production in acutely infected cats. The 275 cats in private catteries were
      monitored for 1 year. Fecal and blood samples were collected every 1 to 3 months
      and assayed by use of RT-PCR and serologic tests to determine patterns of
      coronavirus shedding and cofactors for high frequency shedding. RESULTS: Results
      of the RT-PCR test in SPF cats were directly correlated with fecal extract
      infectivity. Overall, 370 of 894 (41%) fecal samples collected from cattery and
      shelter cats contained infectious levels of coronavirus. Of 121 cats from which
      multiple samples were collected, 11 never shed virus and 35, 65, and 10,
      respectively, shed virus with low, moderate, and high frequency. High frequency
      shedding was associated with age and cattery of origin, but not with sex or
      concurrent disease. Stress associated with parturition and lactation did not
      induce shedding in queens. Kittens did not shed coronavirus before they were 10
      weeks old, even when nursed by shedding mothers. CLINICAL IMPLICATIONS: A large
      proportion of cats in multiple-cat environments shed coronavirus at any given
      time, but most undergo cycles of infection and shedding, recovery, and
      reinfection. Infection is acquired from chronically shedding cats and from
      infectious cats undergoing transient primary infection. Chronically shedding cats
      cannot be identified on the basis of antibody titer or signalment, but must be
      identified on the basis of the results of serial fecal RT-PCR tests.

PMID- 9143536
TI  - Risk factors for feline infectious peritonitis among cats in multiple-cat
      environments with endemic feline enteric coronavirus.
AB  - OBJECTIVE: To determine what risk factors, other than genetic predisposition,
      contribute to the incidence of feline infectious peritonitis (FIP) in private
      breeding catteries and animal shelters. DESIGN: Cats from 7 catteries and a
      shelter were observed monthly for 1 year. At each visit, cats were examined,
      fecal samples were collected for determination of feline coronavirus shedding,
      and blood samples were collected for determination of coronavirus antibody
      titers. Diagnostic tests were performed on all cats that died of FIP. ANIMALS:
      275 purebred or random-bred cats that were kept by private breeder-owners in
      homes. RESULTS: 24 cats died of FIP during the study. Development of FIP was not
      associated with cattery, mean cat number, mean age, sex, cattery median
      coronavirus antibody titer, husbandry and quarantine practices, caging and
      breeding practices, or prevalence of concurrent diseases. However, risk factors
      for FIP included individual cat age individual cat coronavirus titer, overall
      frequency of fecal coronarvirus shedding, and the proportion of cats in the
      cattery that were chronic coronavirus shedders. Deaths from FIP were more
      frequent in fall and winter, and on the basis of analysis of cattery records, the
      number of deaths varied yearly. Epidemics (> 10% mortality rate) were reported at
      least once in 5 years in 4 catteries. CLINICAL IMPLICATIONS: Elimination of FIP
      from a cattery is only possible by total elimination of endemic feline enteric
      coronavirus (FECV) infection. The most important procedure to reduce FECV from
      catteries is elimination of chronic FECV shedders.

PMID- 9143538
TI  - Hypertrophic osteopathy associated with an intrathoracic neoplasm in a rabbit.
AB  - Hypertrophic osteopathy associated with an intrathoracic neoplasm was diagnosed
      in a 7.5-year-old spayed female White New Zealand rabbit. The rabbit was examined
      because it had a swollen foot and was anorectic. An intrapulmonary mass as well
      as periosteal proliferation in the tarsometatarsal region were observed on
      radiography. Histologic examination of necropsy specimens was used to confirm the
      diagnosis of hypertrophic osteopathy secondary to metastatic adenocarcinoma of
      the lungs. To the author's knowledge, hypertrophic osteopathy has not been
      reported in lagomorphs, but should be considered as a differential diagnosis in
      lame rabbits.

PMID- 9143537
TI  - Repair of a facial defect with an interpolation skin flap in a cat.
AB  - A 9-year-old domestic shorthair cat was referred for removal of a rostrally
      located fibrosarcoma on the face, which had previously recurred twice following
      excision. A wide excision was performed, using a neodymium:yttrium-aluminumgarnet
      (Nd:YAG) laser, resulting in a facial defect that could not be closed by primary
      suture. An interpolation skin flap was elevated, using skin from the side of the
      cat's face, and sutured in place over the defect. Recurrence of the tumor at the
      medial canthus of the left eye, which was observed 4 months after surgery, was
      treated by laser excision and cryotherapy. Other recurrences of the fibrosarcoma
      were not noticed for 2.5 years after referral, at which time the cat was
      euthanatized for other reasons. Necropsy revealed that the fibrosarcoma had not
      recurred. In this cat, an interpolation skin flap was useful in repairing a large
      rostral facial defect. Care should be taken when elevating this flap to preserve
      the palpebral nerve.

PMID- 9143539
TI  - Severe nasal hemorrhage in an anesthetized horse.
AB  - An 8-year-old Thoroughbred gelding with colic was anesthetized for surgical
      correction of right dorsal displacement of the ascending colon. Removal of the
      nasogastric tube at the end of surgery resulted in hemorrhage from the nares and
      loss of 24 L of blood. Treatment included administration of acetated Ringer's
      solution, hypertonic saline solution, and dobutamine. A blood transfusion was
      started after hemorrhage was controlled, and arterial pressure was restored to
      the prehemorrhage value, but was stopped after infusion of 2.7 L of blood because
      of a suspected adverse reaction. This case indicates that infusion of balanced
      electrolyte solution, hypertonic saline solution, and dobutamine may maintain
      adequate arterial pressure after severe blood loss, and also supports the
      suggestion that administration of hypertonic saline solution potentiates blood
      loss in the absence of hemostasis.

PMID- 9143540
TI  - Lameness and pleural effusion associated with an aggressive fibrosarcoma in a
      horse.
AB  - An 8-year-old Thoroughbred gelding was admitted for evaluation of chronic
      lameness of the left scapulohumeral joint of 3 months' duration. Radiography
      revealed a radiolucent lesion with the proximal portion of the humerus in the
      area of the metaphysis. Scintigraphy confirmed radiographic findings, with an
      increased uptake of technetium Tc 99m medronate in the proximal portion of the
      left humerus. A preliminary diagnosis of humeral fracture was made. Two weeks
      later, the horse was readmitted for clinical signs of respiratory distress.
      Radiographic and ultrasonographic evaluation revealed masses within the thoracic
      and abdominal cavities. The diagnosis was changed to neoplasm with multiple
      metastases. Because of the unfavorable prognosis, the horse was euthanatized.
      Necropsy findings confirmed an aggressive neoplasm. Special histochemical stains,
      immunohistochemistry, and electron microscopy were required to characterize the
      neoplasm as an anaplastic fibrosarcoma. Findings in this horse illustrate the
      importance of considering neoplasia, resulting in bone lesions, as a possible
      cause of chronic lameness in horses.

PMID- 9143541
TI  - Effects of aminoguanidine on structural alterations of microvessels in peripheral
      nerve of streptozotocin diabetic rats.
AB  - This study was designed to explore the effect of aminoguanidine (AG) on the
      structural abnormalities of microvessels in the sural nerve of streptozotocin
      induced diabetic rats. Diabetic rats were treated with AG (25 mg/ kg, sc) for 16
      weeks, a dose high enough to prevent glycation but also inhibit inducible nitric
      oxide synthase. Non-treated diabetic rats and normal Wistar rats were used for
      comparison. Morphometric analysis disclosed an expansion of vascular and luminal
      areas of endoneurial microvessels in diabetic rats, particularly of large size,
      compared to control rats. These changes were partially but significantly
      corrected by AG treatment. There was no closure of microvessels in diabetic rats.
      The mean ratio of basement membrane area to vascular area was significantly
      smaller in diabetic rats than that in normal control rats and basement membrane
      was not thickened in diabetic rats. The mean ratio of endothelial cell area to
      vascular area was smaller in diabetic rats than that in nondiabetic control rats,
      and it was not influenced by AG treatment. Numbers of microvessels per unit
      endoneurial area in diabetic rats were not different from those of control rats.
      These findings in conjunction with previous reports suggest that alterations of
      nerve blood flow detected in diabetic peripheral nerve may be relevant to
      structural alterations of endoneurial microvessels, which may be an early sign of
      endoneurial microangiopathy. We also consider that AG treatment is beneficial for
      experimental diabetic neuropathy, partially through the correction of endoneurial
      microcirculation.

PMID- 9143542
TI  - Morphology favors an endothelial cell pathway for longitudinal conduction within
      arterioles.
AB  - We examined the morphological parameters of arteriolar endothelial and smooth
      muscle cell dimensions and gap junctional surface areas to obtain an indication
      of the coupling capacity of each cell type. Silver nitrate staining was utilized
      to define cell borders of endothelial and smooth muscle cells in arterioles of
      several vascular beds from two species. From video images of silver-stained
      arterioles, the mean endothelial cell length of hamster cheek pouch arterioles
      (diameter 20 to 110 microns) was found to be 141 +/- 2 microns. Mean endothelial
      cell width was 7 +/- 0.2 microns in the same arterioles. Mean smooth muscle cell
      length in hamster cheek pouch arterioles of diameter 80 to 150 microns was 66 +/-
      3 microns, with an average cell width of 8 +/- 0.2 microns. Dimensions of both
      endothelial and smooth muscle cells varied moderately with arteriole size and
      tissue type, but no general trends were seen. Based on the measured dimensions
      and the specific orientation of cell types within the arteriole, it was
      calculated that in hamster cheek pouch arterioles (60 microns diameter), 6 or 7
      endothelial cell lengths would constitute a 1-mm segment of vessel, whereas
      approximately 140 smooth muscle cell widths would be required to span the same
      length. Estimates of connexin43 gap junctional plaque surface areas in each cell
      type suggest that endothelial cell junctional surface area is approximately eight
      times that of smooth muscle cells. Thus, combined measurement of cell dimensions
      and orientation with estimates of junctional plaque density leads to the
      conclusion that the endothelial cell layer forms a more permissive pathway for
      longitudinal conduction of signals through the blood vessel.

PMID- 9143543
TI  - Use of dynamic capillaroscopy for studying cutaneous microcirculation in patients
      with diabetes mellitus.
AB  - To investigate the relationship between cutaneous microcirculation and
      retinopathy in diabetes mellitus, we studied by dynamic capillaroscopy 35
      diabetes mellitus patients, including 10 patients without retinopathy, 10
      patients with background retinopathy, and 15 patients with proliferative
      retinopathy. We found that (1) cutaneous and retinal microcirculation in diabetes
      mellitus in long-term diabetes mellitus, regressional rather than proliferational
      changes occurred in skin vasculature as compared to that in retina; (2)
      functional impairments of cutaneous microcirculation, that is, decreased resting
      capillary blood cell velocity, peak blood cell velocity, and prolonged time to
      peak capillary blood cell velocity by dynamic capillaroscopy, could be detected
      in diabetes mellitus patients without retinopathy; (3) the degree of tortouosity
      of capillaries, impairment in peak capillary blood cell velocity, and time to
      peak capillary blood cell velocity of cutaneous microcirculation were
      significantly correlated with the gravity of retinopathy in diabetes mellitus
      patients; (4) abnormal leakage of fluorescence in cutaneous microcirculation
      appeared in diabetes mellitus patients with or without abnormal fluorescein
      angiography in retina. In conclusion, dynamic capillaroscopy used in concert with
      ophthalmoscopy and fluorescein angiography can facilitate a comprehensive
      examination of vasculopathy in diabetes mellitus.

PMID- 9143544
TI  - Transmural coupling of fluid flow in microcirculatory network and interstitium in
      tumors.
AB  - The growth of tumors and their response to treatment are determined by delivery
      of diffusible substances to cancer cells and hence by their blood supply.
      Relative to most normal tissues, tumor blood flow is highly heterogeneous.
      Several hypotheses have been postulated to explain this anomalous behavior of
      tumor microcirculation, but the underlying mechanisms for these heterogeneities
      are not fully understood. In this study we consider a potential source of
      nonuniformity in the blood flow: the enhanced fluid exchange between the vascular
      and interstitial space mediated by the high leakiness of tumor vessels which
      could lead to a coupling between vascular, transvascular, and interstitial fluid
      flow. A simple network model is presented to describe the basic features of flow
      through a network of permeable and compliant vessels embedded in an isotropic
      porous medium. Two vascular geometries are considered: a regular mesh of
      identical vessels and a pair of countercurrent vessels of equal diameter. In each
      case, the flow through each vessel of the network is described by Poiseuille's
      law; the transmural flow between the vessels and the external porous medium is
      governed by Starling's law; the fluid movement through the porous medium is
      described by Darcy's law; and the vessel wall is assumed to be elastic. Our
      results show that the behavior of microcirculation may be strongly modified as a
      result of vascular compliance and enhanced vascular leakiness of tumor vessels.
      We found not only that the vascular pressure generates the well-known, high
      central interstitial fluid pressure, but also that the elevated interstitial
      pressure in turn alters the vascular pressure distribution. These changes in
      vascular pressure distribution result in a modification of the blood flow
      pattern. As the leakiness and compliance of the vessels increase, the blood is
      diverted away from the center of the tumor to a more peripheral path. The
      clinical significance of these results is that drug delivery for chemotherapy and
      oxygenation needed for radiotherapy may well be hampered in the central region of
      the tumor, despite the presence of highly permeable vessels in these regions.

PMID- 9143545
TI  - Identification of lymphatic vessels by using a monoclonal antibody specific for
      the human thoracic duct.
AB  - Light microscopic identification of lymphatic vessels of the human small
      intestine was studied immuno-histochemically with a monoclonal antibody specific
      for human thoracic duct (mAb-D) and rabbit anti-human laminin antibody (anti-L).
      Two types of vessels were observed with anti-L; one strongly reacted with
      regularly outlined vessels and the other weakly reacted with irregularly outlined
      vessels and thin walls. Immunoreactivity to mAb-D was strong in the weakly
      reacting vessels, and the strongly reacting vessels did not react to mAb-D.
      Immunoreactivity of lymphatic vessels to anti-L has been reported to be weaker
      than that of the blood vessels; only irregularly outlined vessels which were
      weakly immunostained with anti-L reacted to mAb-D and no cross-reaction to mAb-D
      was observed in the regularly outlined vessels. This indicates that the vessels
      strongly reacting with anti-L are blood vessels and the vessels immunostained
      with mAb-D must be lymphatics. The study shows that it is possible to identify
      lymphatic vessels light microscopically by mAb-D. This method will be useful in
      studying the fine distribution of lymphatic vessels in normal tissue and also in
      pathological tissue such as metastasis of malignant tumors.

PMID- 9143546
TI  - Permselectivity of angiogenic microvessels following alteration of the
      endothelial fiber matrix by oligosaccharides.
AB  - The endothelial glycocalyx, which is composed of integral and peripheral
      glycoconjugates, forms a fibrous matrix that confers macromolecular sieving
      properties on the microvascular wall. Changes in pore size within the matrix may
      regulate macromolecular access to the paracellular and/or vesicular
      transendothelial pathways. We tested the hypothesis that modifications of the
      endothelial glycocalyx might play a role in the ontogeny of endothelial
      permselectivity in proliferating microvessels of the chick chorioallantoic
      membrane (CAM). Accordingly, we evaluated the effects of Dolichos biflorus
      agglutinin (DBA) or Arachis hypogaea agglutinin (PNA) lectin binding, and
      N'N'diacetylchitobiose or hydroxyethyl starch polysaccharide (HES) incorporation
      on CAM endothelial restriction of FITC-dextrans 40 or 150 at Days 4.5 and 5.0 of
      development. Extravasation of FITC-dextrans was determined by recording their
      perivascular interstitial intensities. Following DBA, PNA, and
      N'N'diacetylchitobiose administration, interstitial accumulation of the tracers
      near first-order pre- and postcapillaries, and surrounding the capillaries, was
      similar to that of controls at both Days 4.5 and 5.0. At Day 4.5, pretreatment
      with HES significantly decreased extravasation of FITC-dextran 40. Thus,
      retention of HES molecules within the glycocalyx might tighten the matrix, and
      reduce access of dextran 40 to transendothelial pathways across the angiogenic
      microvessels.

PMID- 9143547
TI  - Laser Doppler flux characteristics at the skin of the dorsum of the foot in young
      and in elderly healthy human subjects.
AB  - In aged human subjects the cutaneous circulation has shown reduced vasoreactive
      capacity when stimulated by heat or ischemia, and autonomic dysfunction
      developing in the elderly was suggested. Should this autonomic dysfunction affect
      the arteriolar vasomotional activity, it might be demonstrated by laser Doppler
      fluxmetry (LDF) at rest. LDF flow motion characteristics at the dorsal foot skin
      were investigated under resting conditions in two subject groups differing in
      age. The younger group (n = 27, aged 25-29 years) showed a resting flux of 3.0 +/
      1.0 Arbitrary Units (AU) and a flux amplitude of 0.34 +/- 0.13 AU. In the
      elderly group (n = 22, aged 60-92 years) both these values were significantly (P
      < 0.05) lower (2.4 +/- 0.5 and 0.18 +/- 0.05 AU, respectively). The flux
      frequency, on the contrary, was similar in both age groups: 4.9 cycles min-1. We
      conclude that the mean resting flux and the mean flow motion amplitude under
      resting conditions at the skin of the dorsum of the foot are significantly
      reduced in an old-age group. The latter finding might be an aging phenomenon
      affecting the microvascular tone and reactivity, and might be one of the elements
      responsible for the attenuated cutaneous vasoreactivity described in elderly
      humans in response to heat and ischemic stress.

PMID- 9143548
TI  - In vivo incorporation from plasma of radiolabeled palmitate and arachidonate into
      rat brain microvessels.

PMID- 9143549
TI  - Novel neuropeptide Y receptor antagonists block vasoconstriction in the hamster
      cheek pouch microcirculation.
AB  - We investigated the efficacy of novel neuropeptide Y (NPY) antagonists to inhibit
      the microcirculatory dynamics of NPY in the hamster cheek pouch microcirculation
      using intravital microscopy and computer-assisted image analysis. Changes in
      arteriolar diameter served as an index of vasomotor alterations. Fluorescein
      isothiocyanate-labeled Dextran 150 served as a tracer for measurements of
      macromolecular transport. GW 383 and GW 1229, two novel NPY receptor antagonists,
      were applied topically in separate experiments. Pretreatment with 10(-5), 10(-6)
      and 10(-7) M GW 383 and with 10(-6) and 10(-8) M GW 1229 attenuated the
      vasoconstriction induced by 10(-7) M NPY in a dose-dependent manner. Furthermore,
      pretreatment with 10(-7) and 10(-8) M GW 1229 significantly inhibited the 10(-9)
      M NPY-induced vasoconstriction. At these doses, the NPY antagonists did not alter
      microvascular permeability. Our results demonstrate that the novel NPY
      antagonists inhibit the vasoconstriction induced by NPY in the hamster check
      pouch microcirculation. We suggest that the inhibition is due to binding of
      antagonists to Y1-type NPY receptors.

PMID- 9143550
TI  - High glucose reduces generation of plasmin activity by mesangial cells.
AB  - Mesangium enlargement is a central feature of diabetic nephropathy and almost
      certainly plays a pathogenic role in this condition. Previous studies have shown
      that mesangium degradation is reduced in a high glucose mileau. Plasmin has been
      shown to play an important role in extracellular matrix degradation, both
      directly and through its ability to activate the matrix metalloproteinases. We
      therefore investigated how high glucose concentration may affect the various
      components of the plasminogen cascade on mesangial cells and whether it impairs
      the ability of the mesangial cell to generate plasmin activity. Result showed
      decreased binding of plasminogen and the urokinase type plasminogen activator to
      the mesangial cell surface while the tissue type plasminogen activator and the
      plasminogen activator-1 associated with mesangial cells were increased. The net
      effect of these changes was a reduced capacity of mesangial cell layers to
      generate plasmin activity in a high glucose environment. We postulate that this
      may be of importance in the reduced mesangium degradation which occurs in
      diabetes.

PMID- 9143551
TI  - Antioxidants attenuate postischemic endothelial cell swelling and luminal
      membrane blebbing in cardiac capillaries.

PMID- 9143552
TI  - Basic fibroblast growth factor-induced angiogenesis in the chick embryo
      chorioallantoic membrane: an electron microscopy study.

PMID- 9143553
TI  - Histamine sustains fMLP-stimulated leukocyte adhesion in rat mesenteric venules
      in vivo.

PMID- 9143554
TI  - Visualization of small vessels in the fingertip of man using color-coded Doppler
      sonography: a new noninvasive tool reducing the diagnostic gap between macro- and
      microcirculation.

PMID- 9143555
TI  - Microvessel mural cell secretions modulate endothelial monolayer permeability.

PMID- 9143556
TI  - Target contact regulates expression of synaptotagmin genes in spinal motor
      neurons in vivo.
AB  - During neuromuscular development, neuronal contact with peripheral targets is
      associated with an increase in synaptic vesicle protein (SVP) gene expression,
      suggesting that target contact and upregulation of SVP genes are causally
      related. To test this idea, we analyzed the developmental expression pattern of
      synaptotagmin (syt) mRNAs in the chick lateral motor column (LMC) using in situ
      hybridization. Syt I mRNA in the LMC is upregulated from Embryonic Day 4.5 (E4.5)
      to E5.5, coincident with the time these neurons begin to make contact with their
      muscle targets. In contrast, levels of mRNA for neurofilament do not change
      during this time. Extirpation of the limb bud prior to motor axon outgrowth
      eliminates the increase in syt I mRNA ipsilaterally. Later in development, there
      is a switch in syt isoform abundance in the LMC, with syt II mRNA being
      upregulated between E15 and E20 and syt I mRNA being downregulated. Our results
      suggest that contact with targets upregulates syt I gene expression during
      neuromuscular synapse formation in vivo, and that a later stage of synaptic
      maturation involves changes in SVP isoform abundance.

PMID- 9143557
TI  - The adult rat hippocampus contains primordial neural stem cells.
AB  - Adult-derived hippocampal progenitors generate neurons, astrocytes, and
      oligodendrocytes in vitro and following grafting into the adult brain. Although
      these progenitors have a considerable capacity for in vitro self renewal, it is
      not known if each lineage is generated by separate committed precursors or by
      multipotent stem cells. By genetic marking, we have followed individual cells
      through the process of proliferative expansion, commitment, and differentiation.
      All three lineages are generated by single marked cells and the relative
      proportions of each lineage can be strongly influenced by environmental cues.
      Differentiation is accompanied by a characteristic progression of lineage
      specific markers and can be potentiated by retinoic acid, elevated cyclic AMP, or
      neurotrophic factors. The ability to genetically mark and clone normal diploid
      hippocampal progenitors provides the first definitive evidence that multipotent
      neural stem cells exist outside of the adult striatal subventricular zone and
      supports the hypothesis that FGF-2-responsive neural stem cells may be broadly
      distributed in the adult brain.

PMID- 9143558
TI  - A transgenic mouse model for human hereditary neuropathy with liability to
      pressure palsies.
AB  - Mutations in the gene encoding peripheral myelin protein 22 (PMP22) account for
      several inherited peripheral neuropathies in humans. We now show that transgenic
      mice expressing antisense PMP22 RNA exhibit modestly reduced levels of PMP22
      together with a phenotype that is reminiscent of hereditary neuropathy with
      liability to pressure palsies (HNPP), a human disease caused by a 1.5-Mb deletion
      of a chromosome 17 region that contains the PMP22 gene. Transgenic antisense
      homozygotes display a striking movement disorder and a slowing of nerve
      conduction that worsens with age. Morphological analysis of peripheral nerves
      demonstrates that a subset of axons have thickened myelin sheaths and tomacula in
      young adults, with significant myelin degeneration detected in older animals.
      Together with other recent work, these data suggest that dosage of the PMP22 gene
      alone underlies the pathophysiology observed in HNPP and related disorders.

PMID- 9143559
TI  - Netrin and netrin receptor expression in the embryonic mammalian nervous system
      suggests roles in retinal, striatal, nigral, and cerebellar development.
AB  - The netrins are laminin-like axon guidance molecules that are conserved among
      Caenorhabditis elegans, Drosophila, and vertebrates and that have chemoattractive
      and chemorepellant properties. To study the possible actions of this gene family
      in the developing and adult mammalian nervous systems, we have cloned a partial
      cDNA which corresponds to a region conserved among chick netrin-1, netrin-2, and
      unc-6 and studied its expression and that of a netrin receptor, dcc, the deleted
      in colorectal cancer gene, in the developing and adult rat CNS. The localization
      of cells expressing netrin or dcc suggests that these genes, in addition to their
      actions in defining the ventral midline, may act in controlling retinal ganglion
      cell axon guidance in the optic nerve, cell migration in the developing
      cerebellum and olfactory epithelium, and development and maintenance of
      connections to the substantia nigra and corpus striatum.

PMID- 9143560
TI  - Clustering of GABAA receptors by rapsyn/43kD protein in vitro.
AB  - Rapsyn, a 43-kDa protein on the cytoplasmic face of the postsynaptic membrane, is
      essential for clustering acetylcholine receptors (AChR) at the neuromuscular
      junction. When transfected into nonmuscle cells (QT-6), rapsyn forms discrete
      membrane domains and can cluster AChR into these same domains. Here we examined
      whether rapsyn can cluster other ion channels as well. When expressed in QT-6
      cells, the GABAA receptor (human alpha 1, beta 1, and gamma 2 subunits) and the
      skeletal muscle sodium channel were each diffusely scattered across the cell
      surface. Rapsyn, when co-expressed, clustered the GABAA receptor as effectively
      as it clustered AChR in previous studies. Rapsyn did not cluster co-transfected
      sodium channel, confirming that it does not cluster ion channels
      indiscriminately. Rapsyn mRNA was detected at low levels in the brain by
      polymerase chain reaction amplification of reverse-transcribed RNA, raising the
      possibility of a broader role for rapsyn.

PMID- 9143561
TI  - Tropomyosin localization reveals distinct populations of microfilaments in
      neurites and growth cones.
AB  - The functional and structural differences between neurites and growth cones
      suggests the possibility that distinct microfilament populations may exist in
      each domain. Tropomyosins are integral components of the actin-based
      microfilament system. Using antibodies which detect three different sets of
      tropomyosin isoforms, we found that the vast majority of tropomyosin was found in
      a microfilament-enriched fraction of cultured cortical neurons, therefore
      enabling us to use the antisera to evaluate compositional differences in neuritic
      and growth cone microfilaments. An antibody which reacts with all known nonmuscle
      isoforms of the alpha Tms gene (Tm5NM1-4) stains both neurites and growth cones,
      whereas a second antibody against the isoform subset, Tm5NM1-2, reacts only with
      the neurite. A third antibody which reacts with the Tm5a/5b isoforms encoded by a
      separate gene from alpha Tms was strongly reactive with both neurites and growth
      cones in 16-h cultures but only with the neurite shaft in 40-h cultures.
      Treatment of neurons with cytochalasin B allowed neuritic Tm5NM1-2 to spread into
      growth cones. Removal of the drug resulted in the disappearance of Tm5NM1-2 from
      the growth cone, indicating that isoform segregation is an active process
      dependent on intact microfilaments. Treatment of 40-h cultures with nocodazole
      resulted in the removal of Tm5NM1-2 from the neurite whereas Tm5a/5b now spread
      back into the growth cone. We conclude that the organization of Tm5NM1-2 and
      Tm5a/5b in the neurite is at least partially dependent on microtubule integrity.
      These results indicate that tropomyosin isoforms Tm5NM1-2, Tm5NM3-4, and Tm5a/5b
      mark three distinct populations of actin filaments in neurites and growth cones.
      Further, the composition of microfilaments differs between neurites and growth
      cones and is subject to temporal regulation.

PMID- 9143562
TI  - Possible benefit of preoperative blood deposit for abdominal surgery.
AB  - Predictors for the need of blood transfusion were analyzed using multiple
      regression analysis in 1689 patients undergoing elective major abdominal surgery
      before the age of 80 years and with a preoperative blood hemoglobin concentration
      above 110 g/L. Rectal surgery for malignant disease and pancreatic surgery (for
      malignant or benign disease) were associated with higher transfusion requirements
      (mean 2.4 units) than other operations (0.6 units). If two autologous units had
      been available in-these patients, the fraction needing allogeneic transfusion
      could have been reduced from 59% to 31%. It would not be effective to predonate
      more than 2 units. For other types of surgery the rate of allogeneic transfusion
      would not have been much reduced, and most autologous blood would have been
      wasted.

PMID- 9143563
TI  - Influence of CO2 pneumoperitoneum on systemic and peritoneal cell-mediated
      immunity.
AB  - Port site metastases could be due to mechanical reasons or impairment of host
      defenses. As it is known that carbon dioxide is toxic for lymphocytes in vitro we
      decided to investigate lymphocyte stress during laparoscopy. Blood samples and
      peritoneal fluids were obtained before and after pneumoperitoneum from 16
      patients undergoing laparoscopic cholecystectomy. Lymphocyte subsets were
      determined by flow cytometry. Propidium iodide was used as a lymphocyte vitality
      test. Cytokines were measured by an ELISA system. Significant falls in the
      absolute lymphocyte count and T3 and T4 lymphocytes occurred on postoperative day
      1 with a quick return to the preoperative value on day 2. T8, natural killer
      cells, T4/T8, and T4+/T8+ counts were stable. Interleukins 1 beta and 6 and tumor
      necrosis factor-alpha were depressed during the two postoperative days.
      Peritoneal lymphocytes were not destroyed by pneumoperitoneum as demonstrated by
      the propidium test, nor were they locally impaired by carbon dioxide. The
      circulating lymphocyte subpopulation decrease favors moderate, brief
      immunodepression. The origin of port site metastases is not immunologic
      depression but, rather, facilitated implantation of malignant cells by
      hyperpressure into raw tissues.

PMID- 9143564
TI  - Technique of video-assisted thoracoscopic surgery for the spine: new approach.
AB  - Although video-assisted thoracoscopy has only recently been applied to treat a
      variety of thoracic spine lesions, many problems and difficulties are encountered
      with this technique owing to limited trocar space and lack of suitable endoscopic
      instruments. Between November 1995 and March 1996, we practiced a new approach
      for video-assisted thoracoscopic surgery, the "extended manipulating channel
      method," for treating 18 patients with thoracic spinal lesions endoscopically.
      The thoracoscopic portals were made larger (usually 3-4 cm) and placed slightly
      more posterior than usual, which allows use of a combination of conventional
      spinal instruments and video-assisted thoracoscopy to enter the chest cavity and
      be manipulated similar to that with techniques used for standard open surgical
      procedures. In our series the endoscopic spinal procedures included biopsy only
      (n = 1), thoracic discectomy (n = 1), multilevel anterior discectomy and fusion
      (n = 1), corpectomy for decompression (n = 4), decompressions and interbody
      fusions (n = 10), and internal instrumentations (n = 4). Throughout the operation
      only one trocar was used for introducing the thoracoscope. There were no
      intraoperative deaths, and no patients showed neurologic deterioration due to the
      procedures. We conclude that such a technique makes thoracoscopy-assisted spinal
      surgery simpler and easier and has proved to be an effective, promising
      procedure. It does not appear to compromise the therapeutic goals set for the
      patients. The intraoperative vessel bleeding can be easily controlled, and the
      number of portals for the procedures can be reduced (on average, three portals
      are enough). Few endoscopic materials were used with our patients, and thus the
      total economic cost to the patients was reduced.

PMID- 9143565
TI  - Economic considerations for the diagnosis and therapy of meniscal lesions: can
      magnetic resonance imaging help reduce the expense?
AB  - With magnetic resonance imaging (MRI) the surgeon has such an effective
      diagnostic tool in the diagnosis of a meniscal lesion that the times of
      diagnostic arthroscopy should be in the past. A total of 823 patients with
      clinically diagnosed meniscal lesions were divided into two groups: group A, 143
      patients underwent MRI and 75 of those arthroscopy; group B, 680 patients, 201
      (30%) of whom were operated after being only clinically examined. MRI was done on
      a Siemens Medical System Magnetom 1.5 Tesla with a 256 x 256 matrix. Spinal echo
      and gradient echo images were performed with slices of 2 to 4 mm thickness. All
      meniscal tears were graded according to Reicher and Crues, respectively. Grades
      III and IV were judged to be positive for a meniscal lesion. Arthroscopy was
      carried out under general anesthesia and the usual technique. The MRI revealed
      the following results: Medial meniscus: accuracy 95%, positive predictive value
      (PPV) 92%, negative predictive value (NPV) 95%, sensitivity 98%, and specificity
      82%, lateral meniscus: accuracy 97%, PPV 92%, NPV 98%, sensitivity 94%, and
      specificity 98%. The overall values for MRI of the medial and lateral menisci
      combined were: accuracy 96%, PPV 93%, NPV 98%, sensitivity 96%, and specificity
      90%. The clinical examination often failed to diagnose a meniscal lesion:
      accuracy 64%, PPV 59%, NPV 89%, sensitivity 96%, and specificity 33% for the
      medial meniscus. For the lateral meniscus the accuracy was 91%, PPV 61%, NPV 98%,
      sensitivity 89%, and specificity 91%. The overall values for the clinical
      investigation of the medial and lateral menisci combined were: accuracy 78%, PPV
      60%, NPV 94%, sensitivity 93%, and specificity 62%. Investigation of all 201
      patients operated from group B with MRI would have cost $160,800. The cost of 30%
      fewer arthroscopies would have been $562,800--in total $723,600. The operation of
      all 201 patients cost $804,000. Hence about $80,000 could have been saved by
      scanning all 201 patients and therefore reduce the rate of diagnostic
      arthroscopies.

PMID- 9143566
TI  - Antibiotic prophylaxis for pit viper envenomation: prospective, controlled trial.
AB  - The efficacy of prophylactic antibiotics for preventing infectious complications
      at the site of pit viper envenomation has not been well studied. We undertook a
      prospective, controlled trial of antibiotic treatment versus no antibiotic
      treatment among 114 victims of crotalid envenomation in Ecuador's Amazon rain
      forest. A group of 59 patients received intravenous gentamicin and
      chloramphenicol, and 55 patients did not. All other aspects of care were
      identical. There were no statistically significant differences between antibiotic
      treated and untreated patients with regard to demographics, delay in treatment,
      clinical and laboratory evidence of severity of envenomation, or use of
      antivenin. Nine abscesses occurred, six in the antibiotic-treated group and three
      in the untreated group. The results of this study did not show any statistically
      significant differences in outcome in terms of the number of abscesses that
      occurred between antibiotic-treated and untreated patients. Based on this lack of
      differences, routine use of prophylactic antibiotics for prevention of infectious
      complications of crotalid envenomation cannot be recommended.

PMID- 9143567
TI  - Surgical treatment for splenic hydatidosis.
AB  - Splenic involvement is rare in patients with hydatid disease even in endemic
      countries. The spleen is the third most commonly involved organ after the liver
      and the lung. In our series splenic echinococcosis represents 5.8% of abdominal
      hydatid disease. During the last 22 years, 14 patients were operated on for
      splenic hydatid cysts in our department. In 10 patients the spleen was the only
      location of hydatid disease; in 2 patients there was concomitant liver hydatid
      disease; one patient had disseminated intraabdominal disease; and one patient had
      a coexisting hydatid cyst in the quadriceps femoris muscle. Plain abdominal
      films, ultrasonography, and computed tomography scans were most useful for
      establishing the diagnosis. All patients underwent splenectomy alone or combined
      with management of cysts at other sites, except for two patients who underwent
      omentoplasty and one patient who underwent external drainage. One patient died
      during the early postoperative period (mortality rate 7%), and three patients had
      minor complications. Splenic hydatid disease should be included in the
      differential diagnosis when a splenic cyst is identified, especially in patients
      with a history of hydatid disease. Surgery remains the treatment of choice to
      avoid serious complications.

PMID- 9143568
TI  - Clinicopathologic study for the assessment of resection for ampullary carcinoma.
AB  - In a prospective observational study including 34 patients with carcinoma of the
      ampulla of Vater, postoperative morbidity, mortality, and long-term survival were
      analyzed to determine the surgical procedure of choice. Surgically related
      postoperative complications were observed in 35.4% of patients after pancreatic
      resection. No patient died within the first 30 days postoperatively, and in
      hospital mortality was 3%. Lymph node metastases were associated only with
      moderate or undifferentiated tumors larger than 0.6 cm in diameter that
      infiltrated beyond the ampulla of Vater. The median follow-up time was 4.3 years.
      The 5-year survival rate for the 31 patients undergoing radical resection was
      62.7%. Multivariate analysis (including the covariates depth of tumor
      infiltration, lymph node metastases, and the ratio of metastatic to dissected
      lymph nodes) demonstrated that only this ratio exerted an independent influence
      on the prognosis (p = 0.001). The present series demonstrates that radical
      resection of ampullary cancer is the procedure of choice even in elderly
      patients. The most important factor influencing the survival rate is the extent
      of the lymph node dissection. The histopathologic investigation of our
      pancreatoduodenectomy specimens demonstrates clearly that local excision of
      ampullary cancer may be indicated only in high risk patients with a pT1, well
      differentiated tumor smaller than 0.6 cm in diameter.

PMID- 9143569
TI  - Single and multiple pyogenic liver abscesses: clinical course, etiology, and
      results of treatment.
AB  - A total of 483 patients with pyogenic liver abscess during the years 1986 to June
      1995 were studied at Chang Gung Memorial Hospital in Kaohsiung: 343 were a single
      abscess and 140 were multiple abscesses. Males were predominantly affected by
      this disease. Abdominal pain was more frequent with the single abscess than with
      multiple abscesses, and jaundice was more frequent with multiple abscesses. Blood
      levels of alkaline phosphatase, bilirubin, and creatinine and the white blood
      cell count were significantly higher in patients with multiple abscesses than in
      those with a single abscess; and the hemoglobin level was higher with single
      abscesses. The single abscess was usually larger than 5 cm, and the multiple
      abscesses were usually smaller than 5 cm. The single abscess was always located
      on the right side (72%) and the multiple abscesses always on the right or both
      sides. Single abscesses mainly had a cryptogenic origin (58.9%) and multiple
      abscesses a biliary origin (45.0%). Liver aspirates revealed Klebsiella
      pneumoniae, Escherichia coli, Streptococcus, Bacteroides, Enterococcus, among
      others. K. pneumoniae was more often found in a single abscess and E. coli more
      often in multiple abscesses. Percutaneous catheter drainage and aspiration
      comprised the main treatment initially, and the failure rate with multiple
      abscesses was higher than that with single abscesses. Surgical intervention
      should be considered for multiple abscesses because of the underlying disease.
      The overall mortality with multiple abscesses (22.1%) was higher than that with a
      single abscess (12.8%). Partial hepatectomy produced a low mortality rate for
      both single and multiple abscesses and should be considered in the presence of
      severe hepatic destruction by an abscess or a stone.

PMID- 9143570
TI  - High preoperative serum alanine transferase levels: effect on the risk of liver
      resection in Child grade A cirrhotic patients.
AB  - Despite careful selection of cirrhotic patients with hepatocellular carcinoma
      (HCC), liver resection remains associated with a greater risk than in patients
      without underlying liver disease. In this study we assessed by multivariate
      analysis parameters associated with in-hospital mortality and morbidity in a
      selected group of 108 Child-Pugh A cirrhotic patients undergoing liver resection
      of HCC. The overall incidences of in-hospital deaths and postoperative
      complications were 8.3% and 48.1%, respectively. By univariate analysis, the
      preoperative serum alanine transferase (ALT) level (p = 0.001) and intraoperative
      transfusions (p = 0.01) were significantly associated with in-hospital death;
      however, only the serum ALT concentration was an independent risk factor. In
      hospital mortality rates in patients whose serum ALT was below 2N (twofold the
      upper limit of the normal value), between 2N and 4N, and more than 4N were 3.9%,
      13.0%, and 37.5%, respectively. An ALT level greater than 2N was predominantly
      observed in patients with a hepatitis C virus infection and significantly
      associated with histologic features of superimposed active hepatitis. Patients
      with an ALT level greater than 2N experienced an increased incidence of
      postoperative ascites (58% versus 32%, p = 0.01), kidney failure (16% versus 0%,
      p = 0.0003), and upper gastrointestinal bleeding (6.4% versus 0%, p = 0.02).
      These results indicate that the preoperative ALT level is a reliable predictor of
      in-hospital mortality and morbidity following liver resection in Child-Pugh A
      cirrhotic patients. Cirrhotic patients with ALT > 2N should undergo only a
      limited resection; if a larger resection is required, those patients should be
      considered for nonsurgical therapy or liver transplantation.

PMID- 9143571
TI  - Preoperative risk assessment of hepatic resection for malignant disease.
AB  - Clinical, laboratory, functional, and volumetric data of 340 consecutive patients
      undergoing hepatic resection for malignant disease between November 1990 and June
      1995 were analyzed. The operative mortality was 3.3% (8/244 patients). Among 178
      patients with liver metastases and 66 with primary hepatobiliary tumors the
      hospital mortality was 4.1% (10/244 patients) and morbidity 22.0% (54/244
      patients). Survival after hepatectomy was strongly influenced by the extent of
      resection quantified by the parenchymal hepatic resection rate. The prediction of
      fatal postoperative complications can be improved for patients with hepatic
      metastases by calculating the liver resection index (sensitivity 75%, specificity
      83%).

PMID- 9143572
TI  - Pathologic and clinical aspects of repair of large incisional hernias after
      implant of a polytetrafluoroethylene prosthesis.
AB  - One of the alternatives for the repair of large incisional hernias is the use of
      a prosthetic material. The present retrospective study relates the experience
      acquired for treatment of large incisional hernias (hernial orifice > 10 cm) with
      ePTFE prostheses. Thirty-eight massive incisional hernias were repaired using
      ePTFE 1 mm thick Soft Tissue Patches. Twenty-four patients received a prosthetic
      patch of 10 x 15 cm, 13 a patch of 15 x 20 cm, and 1 a patch of 20 x 30 cm. In 30
      cases the ePTFE was sutured to the recipient tissues with a double row of
      polypropylene stitches. For the first eight interventions the ePTFE was secured
      using a single row of polypropylene sutures. Pathologic studies of biopsies from
      patients who had undergone surgical reintervention at 40 days, 12 months, and 48
      months, respectively, were done using light microscopy, scanning electron
      microscopy, and immunohistochemistry with human antimacrophage antibodies KP-1.
      The follow-up period for all patients was between 18 and 72 months. There was no
      perioperative mortality. No infection or rejection of prostheses was recorded.
      Seroma was present in four patients. Computed tomography was performed for
      evaluation purposes on 10 randomly selected patients (mean postoperative delay 1
      4 years) and showed the ePTFE encapsulated by newly formed tissue. One of the
      patients suffered from mechanical intestinal obstruction 40 days after implant
      and suffered a recurrence a year later. Three recurrences at the patch-recipient
      tissue interface where the ePTFE had been secured with a single row of
      polypropylene stitches were recorded after 8, 12, and 28 months. At 40 days good
      integration of the biomaterial was observed in the newly formed tissue. On both
      sides of the implant an accumulation of four to six strata of cells was
      appreciable. Some of them were labeled with KP-1. Cell infiltration of the
      prosthesis was restricted to the most exterior third of the patch. There was no
      colonization at the patch-recipient tissue interface. At 12 and 28 months the
      cell barrier had almost disappeared. KP-1-labeled macrophages were scarce.
      Scanning electron microscopy revealed a well defined peritoneum. It may be
      concluded that: (1) a double suture row is recommended to secure the prosthesis;
      (2) ePTFE provides an adequate substrate for the formation of scar tissue; and
      (3) the macrophage response induced by the ePTFE decreases with time.

PMID- 9143573
TI  - Efficacy of fine-needle aspiration biopsy of thyroid nodules: experience of a
      Mexican institution.
AB  - In most centers only selected patients with high risk thyroid nodules undergo
      thyroid surgery, and fine needle aspiration biopsy (FNA) is used to select
      patients for surgical treatment. The aim of the present study was to evaluate the
      impact of FNA on the management of thyroid nodules at our institution. A total of
      872 patients who underwent FNA over a period of 7 years were retrospectively
      analyzed. There were 66 men and 806 women with a mean age of 40 +/- 15 years.
      Altogether 549 patients presented with a thyroid nodule and 323 with multinodular
      disease. The sensitivity and specificity of FNA were 90.0% and 99.8%,
      respectively. The positive and negative predictive values were 98% and 99%,
      respectively, and the accuracy was 99%. Our results are in agreement with those
      of other reports establishing that FNA of the thyroid is safe, reliable, and
      effective for differentiating benign from malignant nodules.

PMID- 9143574
TI  - Perforated peptic ulcer: long-term results after simple closure in the elderly.
AB  - The relative incidence of peptic ulcer perforation in the elderly is rising, and
      the optimal surgical treatment has yet to be defined. To evaluate the long-term
      result after simple closure a follow-up study was initiated at a Swedish
      community hospital. During 1983-1992 a total of 151 patients were admitted with
      perforated peptic ulcer; 92 were elderly (i.e., 70 years or older), 63 of whom
      were operated with simple closure. Mortality at 30 days was 27% (17/63) and the
      total in-hospital mortality 30% (19/63). After a mean follow-up of 79 months, 14
      of the 44 survivors are still alive. So far only three of the survivors have
      required additional hospitalization for complications of peptic ulcer disease.
      Because the rate of serious recurrences is low (14%, 6/44), it is concluded that
      simple closure is an adequate surgical treatment for peptic ulcer perforation in
      the elderly.

PMID- 9143575
TI  - Changes in body composition after gastrectomy: results of a controlled,
      prospective clinical trial.
AB  - To elucidate mechanisms involved in weight development after gastrectomy we have
      prospectively determined changes in body composition during the first year after
      similar operations. A total of 75 patients were enrolled who had a "curative
      operation" for gastric carcinoma; 42 were randomized to have a total gastrectomy,
      23 total gastrectomy with a gastric substitute, and 10 subtotal gastrectomy. All
      reconstructions were done with a Roux-en-Y loop of the jejunum. Body composition
      was assessed preoperatively and at 6 and 12 months after gastrectomy by
      determining total body potassium and total body water. From these estimates, body
      cell mass, extracellular water, fat-free extracellular solids, and body fat were
      calculated with knowledge of the actual body weight and length. Triceps skinfold,
      arm muscle circumference, and grip strength were also measured. Weight loss (10%
      of preoperative weight) occurred early after the operations, after which body
      weight stabilized. Body cell mass remained essentially unchanged over the entire
      study period in contrast to body fat, which decreased by 40% during the first 6
      months after gastrectomy. In accordance with the selective loss of body fat, we
      recorded a significant decrease in triceps skinfold figures and only a minor
      decrease of arm muscle circumference without obvious deterioration in hand grip
      strength. Weight loss after gastrectomy seems to be characterized by selective
      loss of body fat in contrast to other known clinical situations associated with
      impaired nutritional intake. Our observations form a basis for future clinical
      research aimed at preventing weight loss after these operations.

PMID- 9143576
TI  - Quality of life after gastrectomy for gastric carcinoma: controlled study of
      reconstructive procedures.
AB  - The choice of reconstruction after gastrectomy and the significance of remaining
      reservoir function is a matter of controversy. To broaden the criteria for choice
      of treatment, we conducted a prospective randomized clinical trial to determine
      the impact of various gastrectomy procedures on quality of life. Consecutive
      patients (n = 64) eligible for curative gastric cancer surgery were randomized to
      have either a total (n = 31) or subtotal (n = 13) gastrectomy or a jejunal S
      shaped pouch (n = 20) implanted as a gastric substitute. The quality-of-life
      evaluation was based on a battery of questionnaires covering both general and
      specific aspects of life. The patients were rated by one of two psychiatrists who
      were blinded to the patients' group affiliation. Assessments were made on three
      occasions: during the week prior to surgery and 3 and 12 months after the
      surgical intervention. The postoperative complication and mortality rates were
      similar in all treatment groups, with few serious complications recorded.
      Irrespective of type of treatment, the patients suffered from alimentary symptoms
      and functional limitations in everyday life, whereas their mental well-being
      improved after surgery. Patients who underwent subtotal gastrectomy had the best
      outcome, especially with respect to complaints of diarrhea. Patients given a
      gastric substitute after gastrectomy showed no difference from those who had only
      a total gastrectomy. We conclude that despite significant unfavorable
      consequences that follow gastrectomy, patients recover with an improved mental
      status. A pouch reconstruction after total gastrectomy does not improve quality
      of life, but a subtotal gastrectomy has advantages that must be considered when
      the procedure is clinically feasible.

PMID- 9143577
TI  - Causes of death and recurrence after surgery for early gastric cancer.
AB  - The postoperative course of 172 patients with early gastric cancer (EGC) was
      followed for a median 7 years to evaluate the causes of death, incidence and
      patterns of recurrence, and characteristic findings in the recurrent cases. The
      cumulative 10-year mortality rate (+/- SE) was 22 +/- 3.7%. Seven patients (4.1%)
      died of operative mortality, 11 (6.4%) died of a recurrence of the gastric cancer
      and 13 (7.6%) died of unrelated causes. Unrelated causes of death were
      metachronous primary cancer (n = 6), cardiovascular disease (n = 2), pneumonia (n
      = 3), sepsis (n = 1), and car accident (n = 1). Four patients died from gastric
      stump recurrence, three from liver metastases, two from lymph node metastases,
      and two from peritoneal dissemination. Using Cox multivariate analysis,
      histologic type had the most significant effect on recurrence. Although
      influenced by the tumor nature, the EGC prognosis is relatively good. Based on
      the results of this study, particularly in Western institutions, histologic
      examination of resection margins and lymphadenectomy should be improved.
      Moreover, patients must be carefully followed for late recurrence and
      metachronous cancer.

PMID- 9143578
TI  - Surgical management of gastric leiomyosarcoma: evaluation of the propriety of
      laparoscopic wedge resection.
AB  - Laparoscopic surgery has been applied to malignant gastric tumors. To evaluate
      the propriety of laparoscopic wedge resection for gastric leiomyosarcoma it is
      necessary to question whether lymph node dissection is necessary for the surgical
      management of gastric leiomyosarcoma. A retrospective study on open surgery cases
      of gastric leiomyosarcoma was performed to address this issue. The clinical
      records of 28 patients with gastric leiomyosarcoma who had had surgery were
      examined. The patients who underwent open surgery were divided into a systematic
      lymph node dissection (SLND) group (n = 9) and a nondissection (non-D) group (n =
      19). No patient had lymph node metastasis at the time of operation or recurrence,
      and statistical analysis showed no difference between the SLND and non-D groups
      in terms of survival rates. These data suggest that SLND might not be necessary
      for the surgical management of gastric leiomyosarcoma and that laparoscopic wedge
      resection of the stomach can be considered a first-line treatment for gastric
      leiomyosarcoma.

PMID- 9143579
TI  - History of endoscopic and laparoscopic surgery.

PMID- 9143580
TI  - Early postoperative MRI findings following surgery for herniated lumbar disc.
AB  - MRI is routinely used in the evaluation and management of patients with failed
      back surgery syndrome (FBSS). However, its value is unclear in the early
      detection of signs that can negatively affect that later course of surgical
      cases. The purpose of the present study is to describe the MR images of early
      postoperative MRI at 3 days in 30 unselected patients who underwent lumbar
      microdiscectomy, and to correlate the findings with follow up MRI at 8 weeks and
      with final outcome. The findings are correlated with literature data. Early
      postoperative MRI findings were consisting of pseudohernia in 24 patients (80%),
      annular rent in 23 patients (80%), and other non-specific postoperative findings.
      On the late MRI the pseudohernia persisted in 12 patients (50%), the annular rent
      in 4 patients (15%) and asymptomatic pseudo-spondylodiscitis was apparent in 3
      patients (10%) as was a case of true spondylodiscitis. Therefore, early
      postoperative findings have limited value in the management of patients after
      surgery for lumbar disc herniation, since the images were not correlated with the
      immediate clinical course after surgery nor with the late radiological and
      clinical outcome. The evident imaging changes in the early postoperative period
      after lumbar disc surgery limit the accuracy of the interpretation of MRI
      examinations.

PMID- 9143581
TI  - Synovial cysts: clinical and neuroradiological aspects.
AB  - Lumbar and intraneural synovial cysts are uncommon lesions, although their
      incidence has increased since the introduction of MRI. The authors describe the
      results of a study comprising 23 patients with synovial cyst (5 lumbar, 19
      intraneural). Neuroradiological investigations included CT scan and MRI; however,
      it was not always possible to diagnose the nature of the lesion. In 18 cases the
      lesion was removed totally including its capsule; in the other 5 cases it was
      removed subtotally. Seven of the 23 patients presented a total remission of
      symptoms/signs, 11 improved and 5 remained unchanged. The importance of treating
      synovial cysts as radically as possible is discussed together with their most
      significant clinical and neuroradiological aspects.

PMID- 9143582
TI  - Cerebral metastases in childhood malignancies.
AB  - Between January 1982 to June 1994, 154 children with non-CNS malignant tumours
      excluding leukaemias and lymphomas were admitted and treated at the UKMC.
      Symptomatic (10 cases; 6.5%) and non-symptomatic (2 cases; 1.2%) cranial
      metastases (calvarial, dural and/or parenchymal) were seen in 12 (7.8%) cases.
      Among these 12 cases, 7 had intracranial parenchymal metastases (4.5%). Three
      cases had multiple intracranial parenchymal metastases. Only one case had
      infratentorial (cerebellar) metastasis. The patients' ages ranged from 1 to 18
      years (mean age was 7.3 years). The male:female ratio was 5:2. While six
      patients' brain metastases diagnosed during subsequent relapses, one patient
      first presented with brain metastasis. Time elapsed between the diagnosis of the
      primary disease and intracranial metastasis ranged from 0 to 755 days (mean 327
      days). Histopathological diagnoses were confirmed in 4 cases who had craniotomy
      and tumour removal. Mean survival following the diagnosis of intracranial lesion
      was 157 days (ranged from 0 to 412 days). Despite the aggressive treatment,
      including surgery, chemotherapy and radiotherapy, 6 cases died with progression
      or relapse of the intracranial disease. In conclusion, the incidence of
      paediatric intracranial parenchymal metastasis is 4.5%. Prognosis is poor and
      intracranial disease is the primary cause of death.

PMID- 9143583
TI  - Hormone receptors in vestibular schwannomas.
AB  - The possibility that steroid hormones play a role in vestibular schwannoma
      proliferation has been suggested by a number of investigators. There is
      conflicting information about the presence of steroid hormone receptors in these
      tumors. The aim of this study was to examine the expression of androgen,
      progesterone, glucocorticoid and estrogen receptor messenger ribonucleic acid
      levels (mRNA) in twenty-one vestibular schwannomas by either Northern blot
      analysis or the polymerase chain reaction (PCR). Glucocorticoid receptor mRNA was
      expressed in all twenty-one tumors examined. Only two male specimens were
      positive for androgen receptor mRNA expression by PCR-Southern blot analysis.
      Thirty-three percent of the schwannomas (7/21) showed a strong band for
      progesterone receptor mRNA by PCR-Southern blot analysis; there were an equal
      number of males and females in this group. Estrogen receptor mRNA levels were
      undetectable in all tumors examined by PCR-Southern blot analysis. These studies
      suggest that the pattern of steroid receptor expression is different in
      schwannomas than in meningiomas. Individual vestibular schwannomas need to be
      examined for their steroid receptor mRNA expression mRNA expression to know
      whether they will be responsive.

PMID- 9143584
TI  - Multiple intracranial tuberculomas with atypical response to tuberculostatic
      chemotherapy: literature review and a case report.
AB  - Approximately 34 cases of intracranial tuberculomas with paradoxical response to
      antituberculous chemotherapy have been documented worldwide. In most of the
      previously reported cases of this entity an associated tuberculous meningitis has
      been reported. The majority of these patients were children or young adults, who
      had inoperably located intracranial tuberculomas in high risk regions developing
      a few weeks or months after the start of appropriate chemotherapy. 53% of them
      recovered completely, 37% improved with mild neurological deficits and 10% died.
      It is interesting that these intracranial tuberculomas developed or enlarged at a
      stage when systemic tuberculosis was being treated successfully. We report our
      recent experience with these potentially curable tumours of the central nervous
      system. The literature is reviewed and diagnostic and therapeutic considerations
      are discussed. The possible immunological mechanisms of this phenomenon are
      analysed. In conclusion, patients, who are suspected to be suffering from CNS
      tuberculosis should receive a prolonged (12-30 months) course of effective
      antituberculous therapy. Evidence of new intracranial tuberculomas or the
      expansion of older existing lesions require no change in the antituberculous drug
      programme. In such cases systemic dexamethasone as adjuvant therapy for 4 to 8
      weeks is worthwhile and effective. Surgical intervention may be necessary in
      situations with acute complications of CNS tuberculosis such as shunting
      procedures for the treatment of hydrocephalus. When the diagnosis is not firm and
      there is no response to therapy within 8 weeks, a stereotactic biopsy of a
      suspected tuberculoma should be performed. If the largest lesion is not located
      in high risk deep regions of the brain, it should be total removed surgically.
      With this combined management, a satisfactory outcome can be obtained in the
      majority of cases.

PMID- 9143585
TI  - Conservative management of extradural haematomas: effects of skull fractures on
      resorption rate.
AB  - In conservative management of extradural haematomas (EDH), several mechanisms
      were described to explain the resorption of the haematoma. One of these was the
      transfer of the clot into the epicranial space through the skull fracture. In
      this study, the effects of skull fracture and associated intracranial lesions in
      the conservative management of EDH were investigated. Skull fracture and
      associated intracranial lesions were found in 71.11% and 51.1% of the patients,
      respectively. Resorption rate was calculated using an original formula and it was
      0.548 +/- 0.227 in patients with skull fracture and 0.507 +/- 0.170 in patients
      with both skull fractures and additional intracranial lesions. These rates were
      found to be significantly higher than in the patients without fracture. In
      conclusion, in the patients with EDH planned to be managed conservatively, skull
      fracture and additional intracranial lesions must not be thought as risk factors,
      on the contrary, resorption of the clot might be earlier than in the others.

PMID- 9143586
TI  - The relationship between cortical injury and brain tumour. Report of two cases
      and review of the literature.
AB  - We report on two cases of brain tumour and discuss the possible relationship to
      previous cortical trauma. The first patient, a 67-year-old male patient developed
      a glioblastoma at the same site of an open shell-splinter injury of the brain
      after a latency of 48 years. The second patient, a 55-year-old male, had a
      malignant anaplastic astrocytoma in the right frontal lobe 10 years after
      clipping of an aneurysm of the anterior communicating artery. Both cases fulfill
      the criteria of Zulch [52] for the correlation between cortical trauma and
      tumour. We believe that the development of a brain tumour following a cortical
      injury is very rare, although possible. Probably the brain must display some form
      of predisposing genetic alteration for a tumour to develop following a cortical
      injury.

PMID- 9143587
TI  - Ultrastructural study of brain microvessels in patients with traumatic cerebral
      contusions.
AB  - Brain tissue from 11 patients with traumatic cerebral contusions submitted to
      surgery was studied. Control biopsy specimens were obtained from 5 patients
      undergoing ventriculo-peritoneal shunts for "communicating" hydrocephalus. After
      collection, the small fragments were fixed by immersion in glutaraldehyde-osmium
      and embedded in Epon. Semi-thin sections stained with toluidine blue were
      observed with the light microscope. Thin sections stained with lead citrate and
      uranyl acetate were observed using a Jeol electron microscope. In tissues from
      patients with head trauma a clear space most probably corresponding to fluid
      accumulation was systematically observed around microvessels. Ultrastructurally
      endothelial cells from these specimens exhibited signs of marked intracellular
      oedema, tight junctions being intact. Pinocytotic activity was increased, mainly
      at the abluminal surface. Swelling of astrocytic perivascular processes and the
      appearance of macrophagic cells with voluminous lysosomes were also observed. The
      authors conclude that the oedema of endothelial cells probably represent a
      central fact in the pathophysiology of traumatic brain oedema and speculate on
      the putative involvement of stretch-activated receptors in this condition.

PMID- 9143588
TI  - Sudden unilateral blindness after intracranial aneurysm surgery.
AB  - The incidence of unilateral blindness and ophthalmoplegia after aneurysm surgery
      is very rare, but if it occurs, it is mainly caused by intra-operative nerve
      injury. We experienced 6 cases of unilateral blindness immediately after surgery
      for 3 recent years. These patients were classified into Hunt-Hess grade I to II
      except for one patient with III. All patients complained of visual loss with
      varying degree of lid oedema and ophthalmoplegia ipsilateral to the site of
      surgery. Angiographic examination of these patients revealed that the aneurysm
      was located at the internal carotid artery bifurcation in one case and the middle
      cerebral artery bifurcation in five cases. All of them were relatively far from
      the optic nerve. The aneurysm was clipped easily with minimal brain retraction
      via standard pterional craniotomy since the brain was slack in all cases. In all
      cases, injuring the optic nerve during surgery was remote. All patients showed
      evidence of retinal ischaemia on fundoscopy with or without fluorescein
      angiography. The pathophysiology of this ischaemic event is unknown. In our
      patients, we could exclude possible aetiological factors such as abnormal
      systemic and ocular conditions, causing ischaemia in intra-orbital structures,
      increased intracranial pressure, intra-operative hypotension, carotid
      atherosclerosis, and ocular vasospasm etc. Accordingly we speculate that the
      complications seen in our cases were most likely related to intra-orbital
      ischaemia initiated by a collapse of the arterial and venous channels in the
      orbit and/or to direct or indirect contusion on the intra-orbital structures.
      These situations could be produced by inadvertent pressure placed on the eyeball
      with a bulky retracted frontal skin flap. Visual acuity in these patients ranged
      from no light perception to the ability to see objects and detect colour. Their
      conditions were irreversible. The degree of visual recovery seems to be dependent
      on the duration and severity of retinal ischaemia by orbital compression.
      Unfortunately there is no satisfactory treatment. We recommend the use of an eye
      shield to protect ipsilateral eyeball just before aneurysm surgery.

PMID- 9143589
TI  - The effect of endovascular therapy for cerebral arterial spasm, its limitation
      and pitfalls.
AB  - PURPOSE: The effect of endovascular treatment for vasospasm was investigated by
      analysing the results of patients treated in Wakayama City in 1994. MATERIALS AND
      METHODS: Ninety nine patients with ruptured cerebral aneurysms, who survived more
      than one week and were treated in Wakayama City in 1994, were studied. Twenty
      five patients caused symptomatic vasospasm and 25 were treated by endovascular
      therapy, percutaneous transluminal angioplasty (PTA) and/or intra-arterial
      papaverine infusion (IAP). PTA was performed for proximal vasospasm which located
      in the main arterial trunk, such as ICA, M1, BA (n = 3). IAP was chosen for
      distal vasospasm which located mainly in the M2, A1, A2 (n = 12). PTA and/or IAP
      was performed for diffuse vasospasm which located in proximal and distal arteries
      (n = 10). RESULTS: In the proximal vasospasm group, all patients were good to
      moderately disabled on the Glasgow outcome scale (GOS). In the distal vasospasm
      group, 8 patients were good to moderately disabled, and 4 patients were severely
      disabled. The overall results were as follows: 17 (68%), good to moderately
      disabled, 4 (16%), severely disabled, 4 (16%), dead. The morbidity and mortality
      rate was 8/25 (32%) in symptomatic spasm group. CONCLUSION: PTA was very
      effective especially for proximal vasospasm, but IAP was not always effective for
      distal or diffuse vasospasm. Diffuse vasospasm revealed a high mortality rate in
      spite of the endovascular therapy.

PMID- 9143590
TI  - A new table-fixed soft tissue retractor for the anterior cervical spinal surgery.
AB  - Since surgeons sometimes encounter difficulty in keeping self- retaining soft
      tissue retractors in the proper position for anterior cervical spinal surgery, we
      have developed a new, simple soft tissue retractor system, which is fixed to the
      side rails of the operating table via retractor stands. All three joints of the
      retractor can be tightened simultaneously with a single handle. Each of two
      retractor blades can keep its position independent of the other thereby
      maintaining a well-exposed operative field for a long period of time. Fine
      adjustments of the blade position, after fixation of the retractors, is possible
      by sliding the head of the blade assembly along the axis of a ratchet mechanism.
      We have used these retractors in 43 surgical exposures, including 35 for anterior
      cervical fusion, 2 for posterior thoraco-lumbar decompression, and 6 for carotid
      endarterectomy. There have been no complications related to tissue damage.

PMID- 9143591
TI  - Intra-operative electrophysiological diagnosis of spinal root avulsion during
      surgical repair of brachial plexus stretch injuries.

PMID- 9143592
TI  - Inhibition of nitric oxide generation and lipid peroxidation attenuates
      hemolysate-induced injury to cerebrovascular endothelium.
AB  - The mechanisms of hemolysate-induced cerebral injury following subarachnoid
      hemorrhage are just beginning to be clarified. This study examined the injurious
      effects of hemolysate on endothelial cells derived from bovine middle cerebral
      arteries, and evaluated the roles of lipid peroxidation and nitric oxide
      production in this type of damage. Cultured endothelial cells were grown to
      confluency on gelatin-coated plates. The cells were characterized as endothelial
      cells on the basis of morphology. Factor VIII-related antigen staining, and low
      density lipoprotein (LDL) uptake. Additional cells were grown to confluency on
      collagen-coated well inserts, and were treated with hemolysate for 24 hours.
      Prior to hemolysate exposure, cells were treated with: a) an inhibitor of iron
      dependent lipid peroxidation (tirilazad mesylate 100 microM), or b) an inhibitor
      of nitric oxide synthase (either N-nitro-L-arginine: NLA 300 microM, or
      aminoguanidine: AG at 1.5, 7.5, 15 or 150 microM). Permeability of the tracer, U
      14C-sucrose, across the layer of endothelial cells was examined over a 24 hour
      period. Hemolysate induced a significant increase in the permeability across the
      endothelial cell layer. Pretreatment with tirilazad mesylate, NLA, or AG
      attenuated significantly hemolysate-induced changes in the endothelial cell
      barrier. These findings indicate that free radical generation and lipid
      peroxidation are critical participants in hemolysate-induced injury to the
      barrier function of the cerebrovascular endothelium. In addition, the results
      indicate that endothelial cells provide an adequate source of nitric oxide to
      damage their own cellular function. Finally, these findings strongly implicate
      free radical mechanisms in endothelial damage associated with subarachnoid
      hemorrhage.

PMID- 9143593
TI  - In vivo estimation of water content in cerebral white matter of brain tumour
      patients and normal individuals: towards a quantitative brain oedema definition.

PMID- 9143594
TI  - Haemodynamic ischaemia in paediatric moyamoya disease associated with
      renovascular hypertension.

PMID- 9143595
TI  - A paediatric patient with meningioma arising from the cavernous sinus wall.

PMID- 9143596
TI  - Intracranial hypertension syndrome as an unusual form of presentation of spinal
      subarachnoid haemorrhage and subdural haematoma.

PMID- 9143597
TI  - Isolated dural tuberculoma.

PMID- 9143598
TI  - Usefulness of three-dimensional CT for bow hunter stroke.

PMID- 9143599
TI  - Classification of pituitary adenomas.

PMID- 9143601
TI  - The puzzle of HIV-1 subtypes in Africa.

PMID- 9143600
TI  - Simple monitoring of antiretroviral therapy with a signal-amplification-boosted
      HIV-1 p24 antigen assay with heat-denatured plasma.
AB  - OBJECTIVE: Virus load determination has become indispensable for the management
      of HIV patients, but depends on expensive assays of a low throughput. We
      evaluated whether a highly improved HIV-1 p24 antigen detection procedure which
      involves heat-mediated immune complex dissociation and signal-amplification
      boosted enzyme-linked immunosorbent assay (ELISA) was suitable for antiretroviral
      treatment monitoring. DESIGN AND METHODS: Virus load in plasma was determined for
      127 plasma samples taken at 0, 2, 6, 12, 18, 24, 30 and 36 weeks from 23 patients
      with CD4+ T cells < 50 x 10(6)/l who received indinavir 800 mg three times daily
      in addition to prior antiretroviral treatment. Tests included polymerase chain
      reaction (PCR) for viral RNA, measured prospectively with the Roche Amplicor kit,
      and retrospective batch testing of heat-denatured samples for p24 antigen by the
      DuPont HIV-1 p24 Core Profile ELISA linked with a tyramide signal amplification
      step. Particle-associated reverse transcriptase (RT) by the product-enhanced RT
      (PERT) assay was determined as an independent third-opinion viral load marker.
      RESULTS: p24 antigen was detected as sensitively as viral RNA. Overall detection
      during a median observation time of 25 weeks (range, 0-39) amounted to 75.6% for
      antigen and 73.6% for RNA. The antigen detection limit was 0.2 pg/ml. Antigen was
      detectable in all 23 baseline samples, whereas RNA was undetectable in one.
      Antigen and RNA levels in 79 samples positive for both markers correlated with r
      = 0.714 (P < 0.0001). Average changes in levels of p24 antigen and RNA at eight
      timepoints correlated with r = 0.982 (P < 0.0001). In individual patients, the
      two parameters behaved similarly, and in certain cases virtually identically. RT
      activity was measurable in all samples. CONCLUSIONS: The performance of this
      antigen detection procedure is comparable to RNA PCR, thus providing a simple,
      high throughput alternative in monitoring the efficacy of antiretroviral
      treatment.

PMID- 9143603
TI  - Diagnosis of infections caused by Enterocytozoon bieneusi and Encephalitozoon
      intestinalis using polymerase chain reaction in stool specimens.
AB  - OBJECTIVE: To study the usefulness of polymerase chain reaction (PCR) for the
      species identification of microsporidia in stool specimens obtained from HIV
      infected patients with Enterocytozoon bieneusi or Encephalitozoon intestinalis
      infections. SETTING: Infectious disease clinic in a university hospital.
      PATIENTS: Thirty-seven stool specimens from 29 HIV-infected patients with
      microsporidiosis were tested. The diagnosis of microsporidian infection was made
      by light microscopy of stool specimens and species identification was made by
      transmission electron microscopy of duodenal biopsies. Sixty-one stool specimens
      from 45 HIV-infected patients without microsporidiosis served as controls.
      METHODS: PCR was performed using DNA extracted from stools with two primers sets,
      one specific for E. bieneusi and one specific for E. intestinalis. RESULTS: A
      1265 base-pair fragment of the small subunit ribosomal RNA (rrs) gene could be
      amplified from all 31 stool specimens infected with E. bieneusi. In addition, a
      930 base-pair fragment of the rrs gene could be amplified from all six stool
      specimens infected with E. intestinalis. The 61 control stools were negative with
      both primers. CONCLUSIONS: These results suggest that a PCR based assay using
      species-specific primers sets can be used successfully for microsporidian species
      differentiation from stool specimens, thus obviating the need for invasive biopsy
      procedures.

PMID- 9143602
TI  - The beta-core fragment of human chorionic gonadotrophin inhibits growth of
      Kaposi's sarcoma-derived cells and a new immortalized Kaposi's sarcoma cell line.
AB  - OBJECTIVE: Kaposi's sarcoma (KS), a condition often associated with HIV
      infection, is more common in men than in women; pregnancy and sex hormones could
      be involved. Urinary human chorionic gonadotrophin (hCG) has been reported to
      inhibit the growth of KS cell lines, with great variability among preparations.
      Urinary hCG often contains free forms of the hCG subunits and a fragment of the
      free beta-subunit, the beta-core, which may have biological activity. We compared
      the effect of the beta-core fragment, the beta-subunit, recombinant and urinary
      hCG on KS immortal and spindle cells. DESIGN AND METHODS: A new immortal KS cell
      line was phenotypically and karyotypically characterized. The effects on growth
      of this cell line and of primary KS spindle cells by hCG and its purified
      derivatives were tested. Induction of apoptosis was demonstrated using acridine
      orange/ethidium bromide staining. RESULTS: The beta-core fragment harboured the
      most potent growth inhibitory activity on a molar basis. After 72 h of treatment
      with the beta-core, 60-70% of KS cells show apoptotic nuclei. No effects were
      observed on endothelial cells. CONCLUSIONS: The beta-core fragment of hCG proved
      to be the most effective part of the hCG molecule, inducing growth inhibition and
      apoptosis of KS cells. Thus, the beta-core could be the most appropriate hCG
      derivative for the therapy of KS.

PMID- 9143604
TI  - Upregulation of urokinase-type plasminogen activator by endogenous and exogenous
      HIV-1 Tat protein in tumour cell lines derived from BK virus/tat-transgenic mice.
AB  - OBJECTIVE: To demonstrate that Tat modulates the plasminogen-dependent
      proteolytic activity of tumour cell lines derived from BK virus (BKV)/tat
      transgenic mice by affecting the production of plasminogen activators (PA) and
      the PA inhibitor (PAI)-1 and to demonstrate that this occurs through mechanism(s)
      that are distinct from those responsible for transactivating activity of
      extracellular Tat. DESIGN AND METHODS: To assess whether endogenous Tat is
      responsible for PA activity in T53 adenocarcinoma cells, cell cultures were
      transfected with antisense Tat cDNA and evaluated for cell-associated PA activity
      by a plasmin chromogenic assay. The assay was also used to evaluate PA activity
      in T53 cells and T111 leiomyosarcoma cells stimulated by extracellular Tat. The
      type(s) of PA produced were identified by sodium dodecyl sulphate-polyacrylamide
      gel electrophoresis zymography. The levels of PAI-1 were evaluated by Western
      blotting. Tat transactivating activity was measured by a chloramphenicol
      acetyltransferase (CAT) enzyme-linked immunosorbent assay in HL3T1 cells
      containing integrated copies of an HIV-1 long terminal repeat (LTR)-CAT plasmid.
      RESULTS: Transfection of T53 cells with antisense Tat cDNA results in the
      decrease of Tat production and PA activity. Exogenously added Tat increases PA
      levels in T53 and in T111 cells. PA activity was identified as urokinase-type PA
      (uPA). Tat also increases the production of PAI-1 in T111 but not in T53 cells.
      Chloroquine and heparin have different affects on the LTR-CAT-transactivating and
      the PA-inducing activities of Tat. The fusion protein glutathione-S-transferase
      Tat and the mutant Tat-1e, lacking the second Tat exon, cause LTR-CAT
      transactivation without stimulating uPA upregulation. CONCLUSIONS: Tat affects
      the fibrinolytic activity of tumour cell lines derived from BKV/tat-transgenic
      mice by modulating the production of both uPA and PAI-1 via autocrine and
      paracrine mechanisms of action. The capacity of Tat to modulate the plasminogen
      dependent proteolytic activity of these tumour cell lines may contribute to their
      metastatic potential. The uPA-inducing activity of Tat depends upon specific
      biological and structural features of the Tat protein that are distinct from
      those responsible for its LTR-CAT-transactivating activity, suggesting distinct
      mechanisms of induction for the two biological responses.

PMID- 9143605
TI  - CD8+ cells from HIV-2-infected baboons control HIV replication.
AB  - OBJECTIVE: To analyze the CD8+ cell antiviral immune response in HIV-2-infected
      baboons. DESIGN: Baboons were infected with clinical isolates of HIV-2, CD8+
      cells were isolated from phytohemagglutinin (PHA)-stimulated baboon peripheral
      blood mononuclear cells (PBMC). These cells were cultured with PHA-stimulated
      CD4+ cells acutely infected with HIV-2 at several CD8+:CD4+ cell ratios. Control
      of HIV-2 replication was determined by comparing peak levels of HIV-2 replication
      in fluids from CD8+:CD4+ cell cocultures with those in fluids from infected CD4+
      cells cultured alone. RESULTS: CD8+ cells from HIV-2-infected baboons inhibited
      HIV-2 replication in acutely infected autologous CD4+ cells to a significantly
      greater extent than did CD8+ cells from uninfected baboons (P = 0.0001). At the
      beginning of the acute phase of HIV-2 infection, CD8+ cells showed either a
      transient reduction or loss in the antiviral activity. In some cases the CD8+
      cell response enhanced HIV-2 replication. Subsequently, the strength of the CD8+
      cell antiviral activity increased concomitant with a decrease in the HIV-2 load
      in the PBMC. Suppression of HIV replication could be demonstrated with filtered
      fluid from CD8+ cells. Other studies indicated that infected CD4+ cells are lost
      during coculture of CD8+ cells with infected CD4+ cells. CONCLUSIONS: CD8+ cells
      of HIV-2-infected baboons develop substantial anti-HIV-2 activity following HIV-2
      infection, which may account in part for the low frequency of pathogenesis in HIV
      2-infected baboons. Studies to elucidate the mechanism of this CD8+ cell
      antiviral activity suggest that it is mediated in part by a soluble antiviral
      factor, but primarily in association with the loss of infected CD4+ cells.

PMID- 9143606
TI  - The effect of immunization with inactivated hepatitis A vaccine on the clinical
      course of HIV-1 infection: 1-year follow-up.
AB  - OBJECTIVE: To determine the long-term safety of inactivated hepatitis A virus
      (HAV) vaccine in men infected with HIV-1. DESIGN: A 1-year prospective case
      control study. SETTING: Targeted primary care and sexually transmitted diseases
      clinics. PATIENTS: Ninety HIV-1-positive patients who participated in an earlier
      efficacy study of HAV vaccination. CONTROLS: Ninety HIV-1-positive men, matched
      for CD4+ lymphocyte percentage at baseline, who did not receive HAV vaccine.
      INTERVENTION: All cases were assigned to receive two intramuscular doses of 1440
      enzyme-linked immunosorbent assay units of inactivated HAV vaccine (Havrix)
      either 1 or 6 months apart. MAIN OUTCOME MEASURES: Development of AIDS, survival,
      and T-cell subsets after 1 year of follow-up. RESULTS: No significant differences
      were seen between cases and control for the development of AIDS (10.1 versus
      10.7%), deaths (7.3 versus 7.6%) nor for mean decline in circulating CD4+
      lymphocyte count (125 versus 123 x 10(6)/1) after 1 year. CONCLUSIONS:
      Vaccination against HAV appears to be safe in the longer term for HIV-1-infected
      men.

PMID- 9143607
TI  - Characterization and natural course of cardiac autonomic nervous dysfunction in
      HIV-infected patients.
AB  - OBJECTIVE: To examine the degree, pattern, and natural history of cardiac
      autonomic nervous dysfunction in patients infected with HIV. DESIGN: Cross
      sectional and prospective longitudinal cohort study. SETTING: Primary care and
      tertiary referral university centre. PARTICIPANTS: Thirty-five consecutive HIV
      infected patients who had either not yet developed AIDS (15 pre-AIDS patients) or
      who were at the Centers for Disease Control and Prevention (CDC) AIDS stage (n =
      20), and 29 healthy age- and sex-matched HIV-negative controls. METHODS: Computer
      aided power spectral analysis of 15 standardized parameters of heart-rate
      variability (HRV). RESULTS: Pre-AIDS patients as a group did not exhibit any HRV
      parameters to be significantly different from healthy controls (P > 0.017),
      whereas AIDS patients demonstrated reduced HRV in 14 parameters (93.3%) compared
      with healthy subjects (p > 0.017). Median proportion of abnormal HRV parameters
      (< 10th percentile of controls) per individual was 9.1% in pre-AIDS patients and
      61.3% in AIDS patients (P = 0.0347). Progressive CDC stages inversely correlated
      to 10 HRV parameters (66.7%; -0.50 < or = r < or = -0.36; P < 0.05). Follow-up
      testing in 10 pre-AIDS and six AIDS patients after 6-16 months (median, 12.5
      months) did not reveal deterioration of HRV (P < 0.05). A dysautonomia symptom
      score correlated to 10 HRV parameters (66.7%; -0.14 < r < -0.55; P < 0.05).
      CONCLUSIONS: Cardiac autonomic nervous dysfunction is severe in AIDS patients,
      although not significant in pre-AIDS patients. Cardiac autonomic nervous
      dysfunction proceeds with HIV disease progression, although its individual course
      is slow.

PMID- 9143608
TI  - A dose comparison study of a new triazole antifungal (D0870) in HIV-positive
      patients with oral candidiasis.
AB  - OBJECTIVE: This multicentre study evaluated the clinical efficacy and
      tolerability of D0870 in treating oropharyngeal candidiasis in HIV-positive
      patients who had no history of clinical resistance to fluconazole. METHODS: Three
      regimens were evaluated in two phases. In phase I a 50 mg initial dose was
      followed by 10 mg for 4 days (Group 1). In phase II a 100 mg initial dose was
      followed by 25 mg for 4 days (Group 2), or 10 mg for 5 days (Group 3). RESULTS:
      Clinical cure was obtained in 27 patients of a total of 35 (77%) and six other
      patients improved (17%). Two patients at the lowest dose failed and both had very
      low plasma concentration of D0870. No association was found between clinical
      outcome; minimum inhibitory concentration of D0870 pre-therapy for Candida
      albicans, maximum recorded plasma D0870 concentration, cfu of culture or CD4 cell
      count at entry. Overall, 37% of the patients experienced relapse during the 2
      weeks post therapy. Tolerance was excellent. Mild adverse events possibly related
      to the study drug were recorded in five patients. CONCLUSION: D0870 demonstrates
      excellent efficacy at low doses in the treatment of HIV-related OPC and exhibits
      a favourable safety profile.

PMID- 9143610
TI  - Repeat HIV testers at a London same-day testing clinic.
AB  - OBJECTIVE: To compare the characteristics of repeat HIV testers with first-time
      testers in a National Health Service HIV testing clinic in London. SUBJECTS AND
      METHODS: A self-administered questionnaire was distributed to clinic attenders
      between September 1995 and January 1996. The sample was stratified by gender and
      sexual orientation. Repeat and first-time testers were compared with respect to
      recent sexual risk behaviour, reasons for taking the HIV test, condom use,
      knowledge of sex partner's HIV status, and sociodemographic and psychosocial
      variables. RESULTS: Of 965 clinic attenders surveyed, 404 (41.9%) reported at
      least one previous HIV test outside the window period and were classified as
      repeat testers: homosexual men, 62.5% (178 out of 285); heterosexual men, 35.1%
      (126 out of 359); heterosexual women, 31.2% (100 out of 321). Among homosexual
      men, repeat testers were more likely to report the following: two or more
      partners in the previous 6 months for both unprotected anal sex (25.8 versus
      9.3%; P < 0.01) and unprotected oral sex (53.9 versus 37.4%; P < 0.01); ever
      having had a sexually transmitted disease (STD) other than HIV (49.4 versus
      29.0%; P < 0.01); taking the present test "as part of a regular health check'
      (48.9 versus 28.0%; P < 0.01); and knowing others who had tested for or been
      infected with HIV. Repeat testing heterosexual men were more likely to report the
      following: two or more partners in the previous 6 months for unprotected vaginal
      sex (42.9 versus 30.9%; P < 0.05) and unprotected oral sex (41.3 versus 25.3%; P
      < 0.01); ever having had an STD other than HIV (31.7 versus 20.6%; P < 0.05);
      taking the present test "as part of a regular health check' (36.5 versus 26.2%; P
      < 0.05); and knowing others who had tested for or been infected with HIV. For
      heterosexual women, repeat testers were more likely to report ever having had an
      STD other than HIV (25.0 versus 14.5%; P < 0.05), and knowing others who had
      tested for or been infected with HIV. CONCLUSIONS: Repeat testing was associated
      with high-risk sexual behaviour, a previous STD, knowledge of others who have
      tested for or been infected with HIV, and seeking the test as part of a regular
      health check. Factors contributing to repeat testing are multi-faceted and vary
      between groups of different sexual orientation. Use of the impact of knowledge of
      others infected by HIV and the experience of contracting an STD other than HIV
      may guide the development of HIV counselling interventions aimed at reducing
      sexual risk behaviour.

PMID- 9143609
TI  - Functionally relevant changes occur in HIV-infected individuals' alveolar
      macrophages prior to the onset of respiratory disease.
AB  - OBJECTIVE: We have compared the phenotypic and functional changes found in
      alveolar macrophages recovered from the lungs of 39 HIV-positive individuals with
      no respiratory disease with those from 33 HIV-positive individuals with
      pneumonitis and 31 healthy controls. METHODS: Bronchoalveolar lavage (BAL) cell
      cytospin preparations were stained using monoclonal antibody immunoperoxidase and
      double immunofluorescence techniques. Cytokine levels within supernatant BAL were
      determined using enzyme immunoassay. RESULTS: There were marked differences in
      alveolar macrophage phenotype between the three groups. In particular, the
      relative proportion of cells staining RFD1+RFD7- (inducer cells) was reduced in
      the HIV-positive individuals without respiratory disease. This was correlated
      with measures of declining systemic immunity. Patients with pneumonitis had the
      highest levels of measured cytokines [interleukin-1 beta, tumour necrosis factor
      alpha and transforming growth factor (TGF)-beta 2], followed by the HIV-positive
      individuals without respiratory disease. In this latter population a negative
      correlation was found between active (non acid dissociated) TGF-beta 2 and blood
      CD4 cell count. CONCLUSIONS: The differences between the three groups suggest
      that alterations of potential relevance to the pulmonary immune response are
      occurring in alveolar macrophages prior to the onset of respiratory disease. This
      study confirms the importance of investigating asymptomatic HIV-positive
      individuals.

PMID- 9143611
TI  - Assessing participation bias in a sexual behaviour survey: implications for
      measuring HIV risk.
AB  - OBJECTIVES: To assess the likelihood of participation bias in a large population
      based sex survey, and its possible effect on estimates of HIV risk behaviours.
      DESIGN: Construction of general hypotheses about non-participants through
      comparisons of willing and unwilling participants. METHODS: British adults aged
      16-59 years were surveyed in 1990-1991. Interviews consisted of a face-to-face
      section combined with a self-completion booklet (n = 18876). Interviewers
      recorded interviewee embarrassment. Homosexual experience and number of lifetime
      heterosexual partners (grouped 0, 1, 2 or more) were recorded prior to booklet
      offer. Logistic regression was performed, with embarrassment and booklet refusal
      as outcome variables, assessing their association with sexual behaviour after
      controlling for demographic variables. Assuming that, in sexual behaviour, non
      participants are closer to the embarrased and the booklet refusers ('unwilling'
      participants) than to others, these analyses provide an indication of the nature
      of participation bias. RESULTS: Higher refusal an embarrassment rates were
      associated with both reporting no homosexual experience and fewer heterosexual
      partners. CONCLUSIONS: Under our untestable assumption, these results are
      consistent with non-participants being generally at lower risk of HIV infection.
      Methods need to be developed both to reduce participation bias in sex surveys,
      and to incorporate it in analysis.

PMID- 9143612
TI  - Adolescents, sexual behaviour and HIV-1 in rural Rakai district, Uganda.
AB  - OBJECTIVES: To describe the epidemiology of HIV-1 infection among adolescents
      aged 13-19 years, in rural Rakai district, Uganda. STUDY DESIGN: Baseline survey
      and 2-year follow-up (1990-1992) of adolescents in a population-based, open rural
      cohort. METHODS: Annual enumeration and behavioral/serological survey of all
      consenting adolescents aged 13-19 years at recruitment, residing in 31 randomly
      selected community clusters. RESULTS: At baseline, of 909 adolescents present in
      study clusters, 824 (90.6%) provided interview data and serological samples. No
      adolescents aged 13-14 years were HIV-infected. Among those aged 15-19 years,
      1.8% of men and 19.0% of women were HIV-positive. Among young women aged 15-19
      years in marital/consensual union, 21.3% were HIV-positive; this rate did not
      differ significantly from the 29.1% prevalence in those reporting non-permanent
      relationships; prevalence was significantly lower in women reporting no current
      relationship (4.3%). After multivariate adjustment, female sex, age 17-19 years,
      residence in trading centers/trading villages and a history of sexually
      transmitted disease symptoms remained significantly associated with HIV
      infection. Seventy-nine per cent of adolescents provided a follow-up serological
      sample. No young men aged 13-14 years seroconverted during the study; in young
      women aged 13-14 years, HIV seroincidence was 0.6 per 100 person-years (PY) of
      observation. Among young men aged 15-19 years, there were 1.1 +/- 0.6
      seroconversions per 100 PY of observation prior to age 21 years; among women 15
      19 years, the incidence rate was 3.9 +/- 1.0 per 100 PY of observation prior to
      age 21 years. The mortality rate among HIV-positive adolescents aged 15-19 years,
      at 3.9 per 100 PY of observation, was 13-fold higher than that among the HIV
      uninfected. By 1992, knowledge of sexual transmission was almost universal, the
      proportions reporting multiple partners had decreased and condom use had
      increased over baseline. CONCLUSIONS: Adolescents, and young women in particular,
      are vulnerable to HIV infection. Despite reported behavioral changes, HIV
      incidence rates remain substantial, and there is a need for innovative HIV
      preventive measures.

PMID- 9143613
TI  - HIV-associated adult mortality in a rural Tanzanian population.
AB  - OBJECTIVE: To measure HIV-associated adult mortality in a rural population in
      Tanzania. To record the signs and symptoms associated with deaths of HIV-positive
      adults. DESIGN: Prospective cohort study conducted in the context of a randomized
      controlled trial to evaluate the impact of a sexually transmitted disease
      treatment programme. METHODS: A cohort consisting of a random sample of 12501
      adults aged 15-54 years was recruited from 12 rural communities in Mwanza region,
      Tanzania in 1991/1992. Baseline HIV prevalence was 4.0%. The cohort was followed
      up after 2 years to record mortality according to baseline HIV status. A verbal
      autopsy questionnaire was administered for each of the deaths reported. RESULTS:
      A total of 196 deaths were recorded, of which 73 (37%) occurred in HIV-positive
      individuals. Mortality rates per 1000 person-years were 6.0 in HIV-negatives and
      93.5 in HIV-positives. The age-adjusted mortality rate ratio was 15.68 (95%
      confidence interval, 11.18-21.03). The proportion of adult deaths attributed to
      HIV infection was 35% overall and 53% in those aged 20-29 years. Verbal autopsies
      showed that HIV-positive deaths were significantly associated with fever, rash,
      weight loss, anaemia, cough, chest pain, abdominal pain and headache, but the
      specificity of individual symptoms was low. The World Health Organization
      clinical case definition of AIDS was satisfied for only 13 deaths, of which seven
      were HIV-positive at baseline. Only seven respondents reported that the death was
      associated with HIV or AIDS. CONCLUSIONS: This study confirms the strong
      association of HIV infection and mortality in rural Africa, with an annual death
      rate in adult seropositives of over 9%. In this rural population with a
      relatively low HIV prevalence of 4%, HIV has increased overall adult mortality by
      more than 50%. Signs and symptoms associated with HIV deaths were non-specific,
      and the population seemed largely unaware of the contribution of HIV to
      mortality, an important obstacle to prevention efforts.

PMID- 9143614
TI  - Efficiency and rationality in the planning of health care for people with AIDS:
      an application of the balance of care approach. North-East Italian Group for
      Planning of AIDS Health Care.
AB  - OBJECTIVE: To demonstrate the application of an approach for assessing efficiency
      and rationality in the use of resources for the care of patients with AIDS (PWA),
      using data for north-east Italy. DESIGN: An economic methodology, the balance of
      care (BoC) approach, enabled identification of scenarios for the current, planned
      and recommended provision of care in the study region. METHODS: Data on the
      supply and utilization of care by PWA across four locations (inpatient care, day
      care, home care and sheltered accommodation) was collected for a 6-month period
      during 1994. The current BoC measured in care contacts across the locations was
      compared with a planned BoC scenario, derived from the Italian AIDS Health Plan,
      and a recommended BoC scenario based on a delphi expert panel judgement of the
      appropriate care location according to sets of hypothetical clinical and social
      characteristics of PWA. The cost consequences of reallocating patient contacts
      between the current BoC to the recommended BoC was assessed for inpatient and day
      care contacts. RESULTS: There is an overprovision of home care in the planned BoC
      scenario if applied to the study region. The cost consequences of a shift of care
      contacts according to the recommended scenario results in a potential cost
      reduction of 9.2% compared with the current scenario, and hence an expected
      efficiency improvement. CONCLUSION: The BoC approach can be applied to improve
      the efficiency and rationality of resource use in planning care provision for
      PWA.

PMID- 9143615
TI  - Polymerase chain reaction of stool: a powerful tool for specific diagnosis and
      epidemiologic investigation of enteric microsporidia infections.

PMID- 9143616
TI  - Vaccine therapy in early HIV-1 infection using a recombinant canarypox virus
      expressing gp160MN (ALVAC-HIV): a double-blind controlled randomized study of
      safety and immunogenicity.

PMID- 9143617
TI  - Completeness of reporting of AIDS associated with invasive cervical carcinoma.

PMID- 9143618
TI  - HIV exposure category and invasive cervical carcinoma in Italy.

PMID- 9143619
TI  - Nitric oxide production and disease evolution in HIV-infected hemophilic
      patients.

PMID- 9143620
TI  - High prevalence of cutaneous viral infections in AIDS patients with Kaposi's
      sarcoma: insight into the role of human herpesvirus 8?

PMID- 9143621
TI  - A partial explanation for the low number of vertically acquired AIDS cases in
      Amsterdam, The Netherlands.

PMID- 9143622
TI  - Laboratory diagnosis of antibiotic resistant Mycobacterium bovis within 48 h: a
      qualitative change in the approach to mycobacterial diseases in AIDS patients.

PMID- 9143623
TI  - Survival of AIDS patients in an academic unit in Athens, Greece.

PMID- 9143624
TI  - Looking for men in all the wrong places...: HIV prevention small-group programs
      do not reach high risk gay men.

PMID- 9143625
TI  - Genotypic variants of HIV-1 from peripheral blood and lungs of AIDS patients.

PMID- 9143626
TI  - Reducing the incidence of Pneumocystis carinii pneumonia: a persisting challenge.

PMID- 9143627
TI  - Modelling the AIDS incubation time: evaluation of three right censoring
      strategies.

PMID- 9143628
TI  - Mutations associated with zidovudine resistance in HIV-1 among recent
      seroconvertors.

PMID- 9143629
TI  - Side-effects of ritonavir and its combination with saquinavir with special regard
      to renal function.

PMID- 9143630
TI  - Enhanced expression of activation antigens HLA-DR and CD69 on gamma delta T cells
      but impaired interleukin-2-induced upregulation in HIV-1 infection.

PMID- 9143631
TI  - Absence of detectable maternal DNA and identification of proviral HIV in the cord
      blood of two infants who became HIV-infected.

PMID- 9143632
TI  - Motivation and readiness for therapeutic community treatment among cocaine and
      other drug abusers.
AB  - There is currently little empirical research on the effect of motivation and
      readiness on the treatment of different groups of substance abusers. In the
      present study, the CMRS scales are used to assess motivation and readiness for
      treatment of a large sample of primary alcohol, marijuana, heroin, cocaine, and
      crack cocaine abusers admitted to a long-term residential therapeutic community.
      Findings show few significant differences in overall retention or initial
      motivation and readiness. Initial motivation and readiness scores persist as
      significant predictors of short-term retention in treatment across most groups.
      Findings support the TC perspective that the substance abuse problem is the
      person, not the drug of choice, and are consistent with prior research
      emphasizing the importance of dynamic rather than fixed variables as determinants
      of retention.

PMID- 9143633
TI  - Sources of motivation in a couples outpatient alcoholism treatment program.
AB  - This study examines sources of motivation to seek treatment. Participants were
      105 male alcoholics and their non-alcoholic female partners who participated in a
      study of three different approaches to the conjoint treatment of alcoholism.
      Participants' sources of motivation were coded from responses to questions at the
      initial clinical screening interview. Sources of motivation were classified as
      "internal" or "external." More participants had internal sources of motivation
      (74%) than external sources. Participants with internal sources of motivation
      scored higher on the Michigan Alcoholism Screening Test than participants with
      external sources of motivation, but did not differ on other measures of
      pretreatment severity of alcohol problems. About half of the participants (53%)
      cited their partner as a primary source of motivation to seek treatment. Other
      sources of motivation cited were: increasing problems with alcohol, mental health
      problems, and physical health problems. There was greater variability among
      internal sources of motivation than among external sources of motivation.
      Participants' partners but not the male participants themselves, experienced an
      increase in marital satisfaction from pre- to within-treatment when the
      participant was motivated to come to treatment by his partner.

PMID- 9143634
TI  - The Drug Use Screening Inventory for adults: psychometric structure and
      discriminative sensitivity.
AB  - The psychometric structure and characteristics of the adult version of the Drug
      Use Screening Inventory were examined in alcohol and drug abusers (n = 119) and
      normal controls (n = 119). It was found that each of the 10 DUSI domains is
      unidimensional. Inter-item, split half and internal reliability ranged from good
      to excellent. A score of 4 or higher on the Substance Use Domain correctly
      classified 80% of the substance abusers whereas a score of 3 or less accurately
      detected 100% of the normal control subjects. These results demonstrate that the
      DUSI is a practical and psychometrically sound screening instrument.

PMID- 9143635
TI  - Poverty and fatal accidental drug overdoses of cocaine and opiates in New York
      City: an ecological study.
AB  - This ecological study examines the association of the poverty status of urban
      communities in New York City with their mortality rates of accidental drug
      overdoses. Mean annual age-adjusted rates of drug overdoses involving cocaine,
      opiates, or both (n = 1,684) were calculated for each of 59 residential community
      districts in New York City for 1990-1992. A linear regression analysis was
      performed to test the association of the mortality rate with the poverty status
      of the district as measured by the proportion of the district living below the
      1989 U.S. poverty line. Poverty status accounted for 69% of the variance in the
      drug overdose mortality rates of communities (p < .001). This study suggests that
      mortality rates of overdoses involving cocaine and optiates are significantly
      associated with the poverty status of communities in New York City.

PMID- 9143636
TI  - Test-retest reliability of psychoactive substance abuse and dependence diagnoses
      in telephone interviews using a modified Diagnostic Interview Schedule-Substance
      Abuse Module.
AB  - The test-retest reliability of lifetime substance abuse and dependence diagnoses
      obtained by telephone interviewers was investigated. Trained personnel
      administered two identical interviews based on a modified Diagnostic Interview
      Schedule-Substance Abuse Module (DISSAM) approximately a week apart for 100
      respondents, of whom 55 were receiving alcohol or other drug treatment and 45 and
      randomly selected from residential households in one Michigan county. The
      uncorrected agreement for all lifetime dependence diagnoses exceeded 93% for all
      six categories assessed and the more conservative chance corrected agreement
      (Cohen's Kappa coefficient kappa) was .92 (alcohol),.76 (marijuana),.87
      (cocaine), and .71 (other opiates). Kappa coefficients for hallucinogens and
      heroin dependence could not be calculated due to low (i.e., 5% or less) base
      rates. Likewise, kappa was calculated only for a single abuse diagnosis, alcohol,
      with kappa = .42 and 95% agreement. In the interpretation of kappa, the standard
      applied was: kappa ranging from .41 to .60 represented moderate agreement, kappa
      ranging from .61 to .80 represented substantial agreement, and kappa ranging from
      .81 to 1.00 represented excellent agreement. Thus, test-retest reliability was
      excellent for lifetime alcohol and cocaine dependence and was substantial for
      lifetime marijuana and other opiates dependence. These results indicate that
      lifetime psychoactive substance abuse diagnoses can be obtained fairly reliably
      over the telephone using trained lay interviewers.

PMID- 9143637
TI  - A comparison of alcohol, drugs, and aggressive crime among Mexican-American,
      black, and white male arrestees in Texas.
AB  - Few comparative studies exist examining the relationship between substance abuse
      and aggressive behavior under different social conditions. We studied the
      relationship between aggressive crime and substance abuse among Mexican-American,
      black and white male arrestees in Dallas, Houston, and San Antonio, Texas using
      existing 1992 Drug Use Forecasting (DUF) data. The aim of the analysis was to
      predict the outcome of aggressive crime from drug and alcohol-related and ethnic
      group variables within the total male sample (n = 2,364). Results indicated that
      ethnicity was significantly related to aggressive crime. Mexican-American
      arrestees were more likely to be arrested for aggressive crimes than either
      blacks or whites. Drug and alcohol use effects were found across all ethnic
      groups. In general, the subgroup which drank frequently and tested positive for
      drug use was less likely to be charged with aggressive crimes than the other
      subgroups. The psychopharmacological influence of alcohol as a disinhibitor and
      drugs as a inhibitor provides one explantation of the results. Specific ethnic
      subcultural and ecological influences also affect the outcome. Our study strongly
      indicates the heterogeneous character of the drug using population in relation to
      aggression. The variability between subculturally defined subgroups requires
      detained ethnographic field studies in the future to describe the contexts of
      substance use and aggressive behavior.

PMID- 9143638
TI  - Cocaine use immediately prior to entry in an inpatient heroin detoxification unit
      as a predictor of discharges against medical advice.
AB  - Detection of benzyolecgonine, the major metabolite of cocaine, in the urinalysis
      conducted on the first day of an inpatient heroin detoxification treatment
      program was studied as a predictor of discharge against medical advice (AMA).
      With this aim, we conducted a chart-review procedure of 275 heroin dependents
      (DSM-III-R) who received methadone or dextropropoxyphene chlorhydrate to treat
      Opioid Withdrawal Syndrome. Data were analyzed following a case-control design.
      The 49 (17.8%) patients who did not complete the treatment due to discharged AMA
      were characterized by having achieved total heroin abstinence during fewer months
      from the time they began consumption of this substance to the time of
      hospitalization (p = .001). Moreover, those patients who requested discharge AMA
      were characterized by more frequent detection of benzoylecgonine in their urine
      on the day of admission (p = .004). The value of the odds ratio of this
      association was 3.81 (95% CI; 1.30 to 11.04). Lastly, noncompleters due to
      discharge AMA were more likely to be single than ever married (p = .037). The
      logistic regression model confirmed that there is a significant relationship
      between an AMA event and the presence of benzoylecgonine in urine upon beginning
      detoxification and to a shorter duration of the period of total heroin
      abstinence. In the discussion, the influence that recent interruption of cocaine
      consumption has on the decision to drop out of a detoxification program AMA is
      considered.

PMID- 9143639
TI  - Predictors of increases in alcohol-related problems among black and white adults:
      results from the 1984 and 1992 National Alcohol Surveys.
AB  - We examined increases in self-reported alcohol-related problems among black and
      white adult drinkers using data from the 1984 and 1992 National Alcohol Surveys.
      The objectives of the study were to determine whether alcohol consumption,
      drinking norm, or socioeconomic status were related to increases in alcohol
      related problems. Two types of self-reported alcohol-related problems were
      analyzed using regression methods: drinking consequences and alcohol dependence
      symptoms. Results indicated that increases in alcohol consumption were associated
      with increased drinking consequences for white men, but increased consumption had
      little affect for black men. Changes in drinking norms regarding non-social
      drinking were associated with increased in drinking consequences among black men,
      such norms showed little affect on drinking consequences for white men. Despite
      substantial increases in alcohol consumption among black women from 1984 to 1992,
      there were no significant racial/ethnic differences in drinking consequences or
      alcohol dependence symptoms among women. Changes in socioeconomic status were
      however related to increases in drinking consequences and alcohol dependence
      symptoms in women, but not in men. Findings suggest that liberal drinking norms
      may have greater long term consequences for black than white men. Socioeconomic
      status, on the other hand, may have greater explanatory power in predicting
      increases in alcohol-related problems in women than in men.

PMID- 9143640
TI  - Substance abuse and bone marrow transplant.
AB  - The purpose of this retrospective study is to test the hypothesis that lifetime
      substance abuse has an adverse impact on survival after bone marrow transplant
      (BMT). This study included 17 of 468 patients admitted to the Bone Marrow
      Transplant Unit at the Brigham and Women's Hospital in Boston, Massachusetts who
      were identified to have lifetime substance abuse (SA). Seventeen comparison
      subjects were selected from the admissions roster if they matched for disease and
      stage, type of transplant, pretransplant conditioning regimen, and age, but did
      not have SA. The medical records of all 34 patients were then reviewed by expert
      substance abuse clinicians for confirmation of SA and course of transplant.
      Survival time was calculated from the date of BMT admission to the date of last
      contact. Survival data were analyzed through Kaplan Meier survival curves and log
      rank tests for association of survival time with lifetime SA, both before and
      after stratification for history of cigarette smoking and type of transplant. The
      patients with and without SA were well matched for all clinical factors.
      Substance abuse or dependence was confirmed in all 17 patients, with alcohol
      (71%), marijuana (30%), and opiates (30%) identified as the principal substances
      of abuse. Survival analysis demonstrated reduced survival times for patients with
      SA, p = .0022. This difference persisted after stratifying for type of transplant
      and cigarette smoking. Trends in different survival times by type of transplant
      (p = .054) and by history of cigarette smoking (p = .07) were also identified.
      Lifetime substance abuse or dependence appears to have an adverse association
      with survival after bone marrow transplant when other clinical factors are equal.

PMID- 9143641
TI  - Characteristics of dual diagnosis patients admitted to an urban, public
      psychiatric hospital: an examination of individual, social, and community
      domains.
AB  - The study provides descriptive data on a large, diverse sample of dually
      diagnosed patients from an urban psychiatric inpatient setting, utilizing a
      comprehensive array of clinical, social and community functioning measures. The
      intent is to provide more useful and reliable information, particularly
      concerning African-Americans with a dual diagnosis in the public sector. Over a
      one year period, all persons admitted to a public psychiatric hospital with a DSM
      III-R psychiatric diagnosis and a positive screen for substance abuse problems
      using clinical and structured measures (n = 486) were interviewed on the
      Addiction Severity Index (ASI) and other measures to assess community and social
      functioning, alcohol and drug use, psychiatric problems, and service histories.
      The majority of participants were found to have serious economic and employment
      problems, undesirable living arrangements, limited or conflictive family or
      social relationships, and some record of arrest. The ASI problem areas most to
      least in need of treatment were: psychiatric, alcohol and drug abuse, employment,
      family/social, legal, and medical. Substances most often currently abused were
      alcohol, cocaine, and cannabis; there was a high rate of polydrug abuse.
      Participants had experienced a median of 3.0 previous psychiatric
      hospitalizations, fewer outpatient substance abuse treatments, and limited
      community mental health contact. Some subgroup differences based on gender, age,
      and race were found which have implications for community treatment planning. The
      study results document the extreme heterogeneity in the dually diagnosed as well
      as their multiple treatment needs. To better inform treatment planning, future
      research on dual diagnosis should attempt to establish meaningful subgroups
      relevant to service needs and should utilize diverse clinical and functioning
      measures.

PMID- 9143642
TI  - Dose dependent effects of yohimbine on methadone maintained patients.
AB  - Twelve methadone-maintained patients were randomized into a controlled crossover
      study with active and placebo yohimbine 20 mg once a day (n = 4), 5mg three times
      a day (n = 4) or 10 mg three times a day (n = 4) for seven days to evaluate the
      effect of yohimbine on naloxone precipitated opiate withdrawal. The yohimbine
      dose of 10 mg TID was well tolerated and was associated with an average decrease
      of 30% in precipitated withdrawal symptoms.

PMID- 9143643
TI  - Justice system clients of a Toronto youth addiction treatment program.

PMID- 9143644
TI  - BPS, others ponder high failure rate on pharmacotherapy exam.

PMID- 9143645
TI  - Low infant infection rate halts study of perinatal HIV transmission.

PMID- 9143646
TI  - FDA proposes plan for phasing out CFC-containing drug products.

PMID- 9143647
TI  - CDC guidelines focus on prevention of nosocomial pneumonia.

PMID- 9143648
TI  - New guidelines proposed for use of RSV immune globulin.

PMID- 9143649
TI  - APhA house of delegates considers issues from assisted suicide to collaborative
      practice.

PMID- 9143650
TI  - Ethical issues for pharmacists in managed care.

PMID- 9143651
TI  - Standardizing regimens for sliding-scale insulin.

PMID- 9143652
TI  - Managed care backlash.

PMID- 9143653
TI  - Doping control in sports--a perspective from the 1996 Olympic Games.
AB  - Doping-control (DC) procedures, particularly as used at the 1996 Olympic Games,
      are described, and the role of pharmacists in DC is discussed. DC procedures must
      be strict and precisely followed to avoid contamination of samples, the
      appearance of bias, and breaches in security and confidentiality. The process of
      selecting athletes for testing can be random, nonrandom, or a combination of the
      two. Escorts are used to notify athletes of their selection, verify their
      identity, and accompany them to the DC station. When urine specimens are obtained
      for DC, the voiding process must be directly observed. The specimen is checked
      for pH and specific gravity and then processed for shipping to a laboratory to be
      analyzed for banned substances. Medication histories are also obtained, giving
      athletes the opportunity to declare any substance that has been taken for
      legitimate medical purposes. Laboratory analysis involves screening and
      confirmation phases. During the Atlanta Games, roughly 50 pharmacists
      participated in the DC program as escorts or technical officers. It is logical to
      involve pharmacists in DC programs because they can develop and conduct drug
      testing protocols; educate athletes, coaches, and trainers about drug use and
      abuse; and help ensure the safe and effective use of medications. Sophisticated
      doping-control procedures have been developed for athletic competitions, and
      pharmacists have much to offer DC programs.

PMID- 9143654
TI  - Comparison of two brands of test strips for self-monitoring of blood glucose.

PMID- 9143655
TI  - Relationship between home glucose testing and hemoglobin Alc in type II diabetes
      patients.

PMID- 9143656
TI  - Stability of ondansetron hydrochloride and dexamethasone sodium phosphate in 0.9%
      sodium chloride injection and in 5% dextrose injection.

PMID- 9143657
TI  - Stability of nafcillin sodium, oxacillin sodium, penicillin G potassium,
      penicillin G sodium, and tobramycin sulfate in polyvinyl chloride drug
      reservoirs.

PMID- 9143658
TI  - Latex allergy.
AB  - An overview of latex allergy, including methods for preventing reactions and
      reducing exposure to latex, is provided. Latex allergy is a serious medical
      problem for an increasing number of patients and health care workers. From an
      institutional perspective, several precautionary procedures need to be followed
      to ensure safe care for patients and to protect employees from unnecessary latex
      exposure. These include establishing a multidisciplinary committee to develop
      policies and procedures; identifying products containing latex; identifying latex
      sensitive patients and employees as well as those at high risk of developing the
      sensitivity; implementing precautions against allergic reactions to latex;
      educating personnel and patients on latex allergy; and reviewing quality
      assurance data to continually improve precautionary procedures. Pharmacists
      should be involved in developing and implementing these procedures. In
      particular, they can play a major role in the education of health professionals
      and patients. There is a strong need for more information on latex sensitivity,
      especially in the areas of epidemiology, product development, and effectiveness
      of procedures. Each institution, including its pharmacists, must evaluate the
      available information about latex sensitivity and determine appropriate actions.

PMID- 9143659
TI  - Consolidation of pharmacy departments in a regional health system.

PMID- 9143660
TI  - Stability of caffeine citrate injection in polypropylene syringes at room
      temperature.

PMID- 9143661
TI  - Pharmacist's role in rescue efforts after plane crash in Indian Ocean.

PMID- 9143662
TI  - Quantitative analysis of trabecular morphogenesis in the human costochondral
      junction during the postnatal period in normal subjects.
AB  - BACKGROUND: Quantitative histomorphometric features of the bone growth plate in
      the human rib have been investigated in infants, ranging in age from 3-36 weeks
      (mean 18.6 weeks) to provide data currently not available. METHODS: Measurements
      were taken in each histological zone of the growth plate. Data from 20 cases were
      pooled and parameters describing the characteristic features of trabecular bone
      calculated using morphometric formulae. The measurements were made from the
      resting zone of the cartilage to the secondary spongiosa, 3.78 mm from the
      starting point. RESULTS: Cartilage volume fraction decreased from 78% in the
      resting zone to a bone volume fraction of between 20% and 30% in the secondary
      cancellous bone. Cartilage matrix surface increased rapidly in the cartilage and
      bone mineral surface declined in correspondence with the development of primary
      bone. The distance between chondrocyte lacunae was observed to decrease
      throughout the cartilage to a transverse septa thickness of 18 microns in the
      hypertrophic zone. A rapid increase in trabecular thickness to 128 microns was
      observed in the primary spongiosa, the secondary spongiosa ranging between 137
      microns and 168 microns. Spacing, chondrocyte profile transverse diameter,
      increased to 30 microns in the hypertrophic zone, following which an increase in
      trabecular separation to 347 microns was observed in the primary spongiosa. The
      number of transverse intervals between individual chondrocyte lacunae was
      observed to increase in the cartilage to a maximum of 21.3 cartilaginous or
      mineralised septa per mm of growth plate length in the hypertrophic zone.
      Trabeculae in the metaphysis then decreased in number to approximately 1.5
      trabeculae per mm in the secondary spongiosa. CONCLUSIONS: These data thus
      provide new insight into the development of trabecular structure during growth
      and normal values for the comparison of tissue from skeletal dysplasias and
      growth disorders.

PMID- 9143663
TI  - Megamitochondria in the serous acinar cells of the submandibular gland of the
      neotropical fruit bat, Artibeus obscurus.
AB  - BACKGROUND: As part of a continuing investigation of the comparative
      ultrastructure of chiropteran salivary glands, we examined the submandibular
      glands of eight species of neotropical fruit bats in the genus Artibeus. We
      previously described secretory granules of unusual substructure in the seromucous
      demilunar cells of this organ in some species in this genus. In the present
      study, we turned our attention to the serous acinar cells in the same glands.
      METHODS: Specimens of eight species of Artibeus were collected in neotropical
      localities. Salivary glands were extirpated in the field and thin slices were
      fixed by immersion in triple aldehyde-DMSO or in modified half-strength
      Karnovsky's fixative. Tissues were further processed for electron microscopy by
      conventional means. RESULTS: In contrast to seromucous cells, which exhibit
      species-specific diversification in bats of this genus, the secretory apparatus
      and secretory granules in the serous acinar cells are highly conserved across all
      seven species. The single exception involves the mitochondria in one species. In
      this instance, some of the serous cell mitochondria in Artibeus obscurus are
      modified into megamitochondria. Such organelles usually have short, peripheral
      cristae; a laminar inclusion is present in the matrix compartment of every
      outsized organelle. Inclusions of this nature never are present in normal-size
      mitochondria in the serous cells. None of the megamitochondria were observed in
      the process of degeneration. CONCLUSIONS: The giant mitochondria in A. obscurus
      have a matrical structure that is radically different from that of the only other
      megamitochondria reported to occur in bat salivary glands. The factors that lead
      to variation in megamitochondrial substructure in different species, as well as
      the functional capacities of such giant organelles, are unknown.

PMID- 9143664
TI  - Frequency and distribution of articular tissue features in adult human mandibular
      condyles: a semiquantitative light microscopic study.
AB  - BACKGROUND: The adult mandibular condyle is reported to be covered by
      fibrocartilage that develops from growth cartilage present earlier in life.
      Available data on the organization of condylar fibrocartilage are entirely
      descriptive or have been derived from young adult individuals. In order to
      examine the variability in normal appearance, condyles from a representative
      sample of adult humans were analyzed semiquantitatively. METHODS: With a light
      microscope, features of the superficial, intermediate, and deep tissue zones
      subjacent to small contiguous sectors of the articular surface were recorded. The
      distribution of each feature relative to the total surface was then calculated
      and respective data obtained from nine predetermined condylar regions and from
      males and females were compared using analysis of variance. RESULTS: The
      organization of the articular tissue varied significantly in the anteroposterior
      direction only. Unlike during growth, the superficial and deep zones in anterior
      and superior regions mostly contained fibrocartilage, although of markedly
      different appearance. Furthermore, the intermediate zone along about half of its
      anteroposterior extension lacked a distinctly visible layer, because the cell
      density was low and there was dense fibrous tissue or fibrocartilage similar to
      that of the superficial or deep zone, respectively. In these situations, zonation
      of the articular tissue was revealed only by the arrangement of collagen fibers.
      CONCLUSIONS: The appearance of adult condylar articular tissue, in addition to
      varying considerably within and between putative load-bearing and nonload-bearing
      regions, bears only a vague resemblance to the layered organization of the
      growing condyle. Current terminology that refers to that organization, therefore,
      is inappropriate. It is proposed to designate impartially the three articular
      tissue zones of the adult condyle as "superficial," "intermediate," and "deep."

PMID- 9143665
TI  - Morphological and immunohistochemical examination of nerves in normal and injured
      collateral ligaments of rat, rabbit, and human knee joints.
AB  - BACKGROUND: Knee joints possess an abundant nerve supply that relays sensory and
      motor information on such aspects as proprioception, nociception, and
      vasoregulation. Although synovial innervation has been well documented, little is
      known of the nerves that supply the collateral ligaments. METHODS: The morphology
      of rabbit and human collateral ligament nerves was examined by silver
      impregnation. Immunohistochemistry was performed on rabbit and rat collateral
      ligaments to determine the presence of peptidergic nerves in these tissues. A 6
      week gap injury was performed on three rabbit medial collateral ligaments, and
      the localisation of peptidergic nerves in these tissues was determined. RESULTS:
      Irrespective of species or type of ligament examined, the greatest density of
      nerve fibres was found in the epiligament. Nerve fibres commonly accompanied
      blood vessels along the long axis of the ligament and then entered the substance
      of the tissue before ramifying in the deeper layers. Substance P and calcitonin
      gene-related peptide-immunoreactive nerve fibres were found in the collateral
      ligaments of the rat and rabbit. Injured ligaments showed a higher than normal
      level of immunoreactivity in and around the healing zone; however, the nerve
      fibres appeared tangled and truncated. CONCLUSIONS: Like other structures in knee
      joints, collateral ligaments possess a complex nerve supply. The presence of
      peptidergic nerves suggests that ligaments may be susceptible to neurogenic
      inflammation and may be centres of articular nociception.

PMID- 9143666
TI  - Limitations of nls beta-galactosidase as a marker for studying myogenic lineage
      or the efficacy of myoblast transfer.
AB  - BACKGROUND: Nuclear localizing beta-galactosidase (nls beta-gal) is used as a
      marker for studying myoblast cell lineage and for evaluating myoblast survival
      after myoblast transfer, a procedure with potential use for gene complementation
      for muscular dystrophy. Usefulness of this construct depends on the establishment
      of the extent to which nls beta-gal or its mRNA may be translocated from the
      nucleus that encodes it to other non-coding myonuclei in hybrid myofibers and the
      ease with which the encoding and non-coding myonuclei can be distinguished.
      Previous in vitro studies (Ralston and Hall 1989. Science, 244:1066-1068) have
      suggested limited translocation of the fusion protein. We re-examined the extent
      to which nls beta-gal is translocated in hybrid myofibers, both in vitro and in
      vivo, and evaluated the extent to which one can rely on histochemistry to
      distinguish encoding from non-coding nuclei in these myofibers. METHODS: Myotubes
      formed in co-cultures of a myoblast line (MM14 cells), stably transfected with a
      construct consisting of a nls beta-gal under the control of the myosin light
      chain 3F promoter and 3' enhancer (3FlacZ10 cells), and [3H]-thymidine-labeled
      parental MM14 cells (plated at ratios of 1:6 or 1:20, respectively) were reacted
      with X-gal. After autoradiography, the distance over which nls beta-gal was
      translocated in hybrid myotubes was determined. In vivo translocation of nls beta
      gal was evaluated by injecting [3H]-thymidine-labeled 3FlacZ10 myoblasts into the
      regenerating extensor digitorum longus muscle of immunosuppressed normal and mdx
      (dystrophin deficient) mice. Sections stained with X-gal and subjected to
      autoradiography permitted determination of the extent of nls beta-gal
      translocation in hybrid myofibers. RESULTS: In vitro: All nuclei in > 92% of
      hybrid myotubes showed evidence of nls beta-gal after exposure to X-gal,
      suggesting extensive translocation. Within hybrid myotubes, MM14-derived
      myonuclei approximately 350 microns from a 3FlacZ10-derived myonucleus showed
      evidence of nls beta-gal. In vivo: Similar translocation of nls beta-gal was
      observed in vivo. One week after myoblast transfer, donor-derived myonuclei were
      distinguishable from host-derived myonuclei containing nls beta-gal by the
      greater accumulation of reaction product in donor myonuclei after X-gal staining.
      However, 2 weeks after injection, host myonuclei often contained a significant
      amount of nls beta-gal, and accumulation of reaction product could not be used as
      the criterion for identification of donor myonuclei. CONCLUSIONS: Translocation
      of nls beta-gal (or its mRNA) is significantly greater than previously reported
      (Ralston and Hall 1989), resulting in large numbers of nls beta-gal positive non
      coding myonuclei in hybrid myofibers. One week after myoblast transfer,
      distinguishing between nls beta-gal encoding and non-coding myonuclei in hybrid
      myofibers after X-gal staining of sectioned muscle is feasible; however, by 2
      weeks, nls beta-gal increases in host myonuclei, making identification of donor
      derived myonuclei problematic. Translocation of nls beta-gal to non-coding
      myonuclei in hybrid myofibers must be considered when nls beta-gal is used for
      studies of myogenic lineage or the efficacy of myoblast transfer therapy,
      particularly if long-term survival of hybrid myotubes is required.

PMID- 9143667
TI  - Immunocytochemistry of extracellular matrix components in the rat seminiferous
      tubule: electron microscopic localization with improved methodology.
AB  - BACKGROUND: Cell-cell interactions between Sertoli, myoid, Leydig, and germ cells
      are thought to be essential for spermatogenesis. These cells interact with each
      other through the extracellular matrices (ECMs) of the testicular lamina propria,
      which thus may have an important function in spermatogenesis. For an
      understanding of the role of ECMs in spermatogenesis, it is important to
      investigate the molecular constitution of the testicular ECM. We examined the
      distribution of type IV, V, and VI collagens (Cols), laminin (LM), fibronectin
      (FN), and heparan sulfate proteoglycan (HSPG) in the rat testicular lamina
      propria. METHODS: Adult rat testes were fixed with 4% paraformaldehyde and 0.2%
      glutaraldehyde. Ultrathin frozen sections were made and immunolabeling was
      performed according to the method of Tokuyasu (1986 J. Microsc., 143:139-149).
      Alternatively, for preembedding immunocytochemistry, we used labeling with
      nanogold, followed by silver enhancement and gold toning. The tissues were then
      fixed with osmium and embedded in Epon (Sawada and Esaki 1994 J. Electron
      Microsc., 43:361-366). These specimens were examined in a JEOL JEM-100C
      transmission electron microscope operated at 80 kV. RESULTS: Col IV, LM, and HSPG
      were localized in the basement membranes of the seminiferous tubule (ST-BM) and
      in the BM of myoid cells. Cols V and VI, and FN were localized both in the
      connective tissue between the seminiferous tubule and the myoid cells (tubule
      myoid connective tissue) and in the connective tissue between the myoid cells and
      the lymphatic endothelial cells (myoid-endothelium connective tissue).
      Furthermore, statistical analysis of the micrographs of immunogold labeling for
      Col IV, LM, and FN around the ST-BM suggested that the Col IV molecule is located
      uniformly in the ST-BM, whereas the LM molecule is distributed mainly in the
      lamina rara of ST-BM, and the FN molecule appears to be present predominantly in
      the tubule-myoid connective tissue. CONCLUSIONS: Distinct distribution patterns
      were observed for each antigen within the testicular lamina propria at the
      ultrastructural level. However, localization of some components was not
      consistent with localizations reported by others.

PMID- 9143668
TI  - Architecture, elastic fiber, and collagen in the distal air portion of the lung
      of the 18-month-old rat.
AB  - BACKGROUND: The increase in the distal air spaces which takes place with age is
      the only sufficiently documented datum for differentiation between the senile and
      the adult lung. There are other pulmonary components which may be modified as the
      lung enters the phase of old age, but they have not as yet been sufficiently
      studied. The purpose of this study is to make a morphometric comparison between
      the wall thickness of the distal air spaces, elastic fiber, and collagen in lungs
      of rats of between 5 and 18 months of age. METHODS: The left lung of each rat was
      histologically processed for light microscopy. The sections were contrasted using
      methylene blue, resorcinfuchsin and Sirius red. Systematic randomized sampling
      was used for the selection of the histological fields studied. Morphometric
      variables were studied, and were systematized into three groups, namely:
      variables related with the alveolar architecture, variables which quantify
      elastic fiber, and those which quantify collagen. RESULTS: The old animals
      exhibited significant differences (p < 0.05) in the following variables: 1. In
      relation with the alveolar architecture, mean linear intercept, alveolar chord
      and wall thickness increased, whereas internal alveolar perimeter and tissue
      density decreased. 2. The relation elastic fiber density/lung tissue density
      increased. None of the variables which quantify collagen displayed significant
      differences. CONCLUSION: Our data lead us to consider that the lungs of the old
      animals displayed, not only an enlargement of the distal air spaces, but also a
      thickening of the alveolar wall and an increase in elastic fiber in relation to
      the rest of the lung tissue.

PMID- 9143669
TI  - Ultra-high-resolution scanning electron microscopy of the sarcoplasmic reticulum
      of the rat atrial myocardial cells.
AB  - BACKGROUND: The sarcoplasmic reticulum (SR) of mammalian ventricular and atrial
      muscles share common features but also differ because T-tubules are rare and
      extended junctional SR is exclusively seen in the atrium. This scanning electron
      microscope (SEM) study was undertaken to clarify the three-dimensional
      organization of the rat atrial SR system. Specific preparations were examined
      with an ultra-high-resolution SEM. METHODS: Fixed right rat atria were frozen,
      fractured, and macerated by the aldehyde-osmium-DMSO-osmium method to remove
      myofibrils and cytoplasmic matrix. Left exposed were mitochondria, SR, and
      sarcolemma. Dried specimens were then impregnated by osmium-hydrazine and
      examined without metal coating. RESULTS: In place of conventional T-tubules, a
      prominent type of sarcotubules, Z-tubules, were found at the Z-line level.
      Branches from these tubules joined the cisternal SR, which was 100-300 nm in
      diameter and localized near the Z-line, and formed extensive SR meshworks and
      polygonal patches. Bulbous swellings, the corbular SR, were also evident.
      Sarcotubular reticulum completely surrounded each myofibril. The
      intermyofibrillar SR, especially Z-tubules, joined the peripheral subsarcolemmal
      SR, which was also arranged as a meshwork and was closely apposed to the
      sarcolemma. CONCLUSIONS: These SEM observations confirm the organization of the
      rat atrial SR system and present new, detailed, three-dimensional images of Z
      tubules, cisternal SR, extended junctional SR, and peripheral SR, which provide
      further structural insight.

PMID- 9143670
TI  - Apoptotic cell death during the estrous cycle in the rat uterus and vagina.
AB  - BACKGROUND: Rodent uterus and vagina show marked histological changes during the
      estrous cycle. Apoptotic cell death has been demonstrated in hamster and rat
      uterine epithelium during the estrous cycle by electron microscopy: numerous
      epithelial cells undergo apoptosis at estrus. We examined cell death and cell
      proliferation in rat uterus and vagina during estrous cycle. METHODS: To examine
      the rate of proliferation in uterine and vaginal cells at each estrous stage, the
      numbers of cells at metaphase were counted separately in epithelial and stromal
      cells. We identified the apoptotic cells in uterus and vagina at each estrous
      stage by using DNA fragmentation, in situ DNA 3'-end labeling, and electron
      microscopy. RESULTS: Mitotic rates in uterine luminal and glandular epithelial
      cells were low at metestrus and estrus, respectively. Intense fragmentation was
      found in the uterus at metestrus and in the vagina at proestrus and metestrus. In
      uterine luminal and glandular epithelial cells, apoptotic index showed peaks at
      metestrus and estrus, respectively. In vaginal epithelial cells, many apoptotic
      cells were encountered in the superficial layer at proestrus, which may
      contribute to keratinization. In the middle and basal layer of vaginal epithelial
      cells, apoptotic index was high at metestrus, when mitotic rate was low. Electron
      microscopy confirmed the results of the labeling studies. CONCLUSIONS: Apoptotic
      cell death was encountered in the uterus and vagina during estrous cycle in rats.
      There is an inverse correlation between cell death and cell proliferation in rat
      uterine and vaginal epithelial cells during the estrous cycle.

PMID- 9143671
TI  - Temporal and spatial asymmetries in the initial distribution of mesenchyme cells
      in the atrioventricular canal cushions of the developing chick heart.
AB  - BACKGROUND: We investigated potential early asymmetries in the distribution of
      mesenchymal cells within the inferior and superior AV cushions in the developing
      chick heart. METHODS: Chick embryos stages 16-20 HH were fixed, embedded in
      polyacrylamide, and the cell nuclei stained with propidium iodide. Cells counts
      were determined within the cardiac jelly of the atrioventricular canal (AV) by
      laser confocal microscopy in coronal planes spanning its entire length. RESULTS:
      Our data show at the different stages studied, 16-20 HH, that the inferior AV
      cushion invariably contains more cells than the superior AV cushion. In the
      inferior cushion, the cell distribution is bimodal, i.e., the proximal and distal
      regions have more mesenchymal cells than the middle part of the AV canal. In the
      superior cushion, there is a increasing gradient of mesenchymal cells along the
      longitudinal axis from the atrium to the ventricle. CONCLUSIONS: Our findings
      reveal that the temporal and spatial characteristics of mesenchyme formation in
      the inferior vs. superior AV cushion are different. This asymmetry suggests
      several potential hypotheses: (1) the distribution of the inducer molecule or its
      receptor has a distribution similar to that of mesenchymal cells, (2) the
      extracellular matrix has a differential composition or regionally-specific
      physical associations, (3) the endocardium is heterogeneous with respect to
      transformation capacity, or (4) these patterns result from an earlier inductive
      event. The potential importance of the observed asymmetries in the distribution
      of AV mesenchyme is discussed relative to localization patterns of molecules
      critical to successful cardiac morphogenesis and remodeling.

PMID- 9143672
TI  - Factors influencing fetal macrophage development: III. Immunocytochemical
      localization of cytokines and time-resolved expression of differentiation markers
      in organ-cultured rat lungs.
AB  - BACKGROUND: Exogenous TNF alpha, IL-1 beta, M-CSF, and GM-CSF all stimulate
      growth of macrophages arising in explanted fetal rat lungs. The present study
      examines the intrinsic availability of these factors in intact and organ-cultured
      lungs and utilizes expression of cytokines and marker proteins to explore the
      differentiation pathway followed by phagocytes in vitro. METHODS: Factors and
      markers were localized immunocytochemically in paraffin sections of 14- and 15
      day fetal rat lungs and lungs organ-cultured up to 7 days on serum-containing
      medium solidified with agar. Western analyses for the cytokines were performed on
      lysates of whole 15-day lungs, and in situ hybridization of M-CSF receptor mRNA
      was carried out in sections of 14 + 2 day cultured lung. RESULTS: IL-1 beta, M
      CSF, and GM-CSF were demonstrated in the stroma of intact and cultured lungs by
      immunostaining, results confirmed by Western blotting. TNF alpha appeared to be
      absent. A few precursors (angular cells) expressed the macrophage lineage marker
      RM-1 as early as day 14, and immunostaining became stronger and more widespread
      as the population matured and expanded in cultures. The OX-6 antibody to Ia
      antigen first reacted with macrophages in 14 + 1 day explants, and within a week
      50% of cells were positive. M-CSF and mRNA for its receptor were present at 14 +
      2 days, as was PDGF, which had been demonstrated in the stroma and epithelium
      prior to explantation. Definite reactivity for IL-1 beta and GM-CSF followed at
      14 + 4 and 14 + 5 days. CONCLUSIONS: M-CSF, GM-CSF, and IL-1 beta, but not TNF
      alpha, are available to replicating angular cells before and during their
      conversion to phagocytes. Fetal lungs thus qualify as a hematopoietic tissue
      supportive of macrophages. The path of differentiation pursued in organ cultures
      involves early expression of structural elements (RM-1, Ia antigen) followed by
      synthesis of cytokines of the TNF alpha cascade. Immunostaining for both RM-1 and
      OX-6 suggests that fetal lung macrophages share a common heritage with antigen
      presenting pulmonary dendritic cells.

PMID- 9143673
TI  - Morphological changes during hepatocellular maturity in neonatal rats.
AB  - BACKGROUND: Hepatocellular maturation is characterised by the progressive
      transition from an architecture in which hepatocyte plates are at least two cells
      thick to the familiar adult pattern in which liver cell plates are predominantly
      single-cell in thickness. A similar process also has been noted during
      compensatory hyperplasia following damage, or destruction to the hepatic
      parenchyma. The pathological events that underlie these processes remain
      inadequately explained. A new morphological approach has been developed to study
      the maturity of rat neonatal livers in order to identify the factors which govern
      the structured morphogenesis of the liver in greater detail. METHODS: Sections of
      hepatic tissue obtained from the left lateral and right posterior lobes from
      neonatal rats were studied at 8, 10, 11, 13, 14, 18, 23, and 28 days postpartum.
      These were mounted, fixed, and stained with haematoxylin and eosin and analysed
      using a modified point-counting technique. Following validation of the technique,
      the proportion of single-cell plates to double-cell plates was then calculated at
      each time point. RESULTS: Liver sections from 8-day neonatal rats had the lowest
      percentage of single-cell thick plates of 16.9 +/- 4.6% and the lowest standard
      deviation (mean +/- SD). The hepatic architecture had fully matured by 28 days
      and was characterised by predominantly single-cell plates (84.6 +/- 4.6%) lining
      the hepatic sinusoids. During the intervening time, the standard deviations
      increased significantly, peaking between 18-23 days, and reflected the rapidly
      changing morphology of the liver during this maturation process of the conversion
      of double-cell plates to single-cell plates. CONCLUSIONS: It is concluded that
      the process of hepatocellular maturity in the neonatal Sprague-Dawley rat is
      reproducibly complete by 28 days and that further studies may now be conducted to
      determine the anatomical and pathophysiological changes that govern this
      important transition.

PMID- 9143674
TI  - Expression of the cholinergic signal-transduction pathway components during
      embryonic rat heart development.
AB  - BACKGROUND: Previous studies showed that acetylcholinesterase (AChE) activity is
      present in the downstream (arterial) part of the embryonic chick and rat heart,
      but its functional significance was unclear. To establish whether other
      components of a cholinergic signal-transduction pathway are present in the
      embryonic heart, we localised the mRNAs encoding choline acetyltransferase
      (ChAT), acetylcholinesterase (AChE), and the muscarinic receptor isoforms
      (mAChRs; m1-m5). METHODS: Messenger RNA detection and localisation by in situ
      hybridisation and reverse transcriptase-polymerase chain reaction were employed.
      RESULTS: Expression of ChAT and AChE mRNAs was observed from 15 embryonic days
      onward in the neural tissue covering the dorsocranial wall of the atria.
      Muscarinic receptors (m1, m2, m4) were observed at the same localisation as AChE
      and ChAT mRNAs, both during embryogenesis and after birth. In addition, m1 and m4
      mAChRs showed a low level of expression in the atrial myocardium during the fetal
      period. No expression of the m3 or the m5 mAChRs was observed in or near the
      embryonic hearts. ChAT, AChE, and mAChRs (m1, m2, m4) mRNAs always colocalised in
      the cardiac ganglia. However, none of these mRNAs was found at a detectable level
      in the outflow tract and/or the ventricular trabeculations. CONCLUSIONS: The AChE
      activity in the arterial part of the embryonic heart is probably synthesised
      elsewhere and subserves a function different from the hydrolysis of locally
      produced acetylcholine.

PMID- 9143676
TI  - Ultrastructural changes in the nerve fiber population of anastomosed vagal and
      spinal accessory nerves in the sheep.
AB  - BACKGROUND: The ultrastructure of the vagal and spinal accessory nerves was
      studied 1) in normal sheep and 2) in sheep in which an experimental crossed-nerve
      anastomosis had been made by sectioning the supranodose vagal and spinal
      accessory nerves, then suturing the distal end of the vagal nerve to the distal
      end of the spinal accessory nerve, and allowing time for regeneration to occur.
      This study was carried out in order to analyze the modifications liable to occur
      when this technique is used and to specify the origin and the nature of the
      fibers that colonize the spinal accessory nerve. METHODS: The study was performed
      in 4- to 5-month-old-sheep. After the surgical procedure, the animals were housed
      indoors during 1 year until their sacrifice by fixative perfusion. Then, nerve
      samples were dissected out, processed for electron microscopy, examined, and
      systematically photographed. After printing, the diameters of the nerve fibers
      were determined. RESULTS: In sheep, the ratios of nonmyelinated to myelinated
      fibers (NF/MF) in the infranodose and supranodose vagal nerve and accessory
      spinal nerve were 1.21, 1.67, and 3.21, respectively. In both parts of the vagal
      nerve, the myelinated fibers had a unimodal diameter distribution around a peak
      of 4 microns; whereas, in the spinal accessory nerve, they were distributed
      bimodally, and 53% had values of 15-18 microns. After making the above
      anastomosis, the centrifugal vagal fibers degenerated, and the NF/MF ratios
      increased in the centripetal infranodose vagal nerve, in the reinnervating
      supranodose vagal nerve, and in the reinnervated spinal accessory nerve
      (approximately 1.87, 1.72, and 6.04, respectively). In all of these nerves, the
      myelinated fibers had a unimodal distribution with a peak at 4 microns, as in the
      vagal nerve of normal sheep. CONCLUSIONS: These results reveal the large part
      taken by the nonmyelinated fibers in the nerve fiber population of the vagal
      nerve and support the vagal origin of the fibers reinnervating the spinal
      accessory nerve.

PMID- 9143675
TI  - Peritoneal lymphatic stomata of the diaphragm in the mouse: process of their
      formation.
AB  - BACKGROUND: Lymphatic stomata are channels connecting the peritoneal cavity with
      the lymphatics in the diaphragm. The process of sequential formation of the
      stomata has not been studied. The objective of this study was to examine the
      morphogenesis of the lymphatic stomata in mice. METHODS: Ultrathin sections of
      diaphragms from ddY mice obtained on embryonic day 18 and postnatal days 0, 4,
      and 10 were observed with a transmission electron microscope. RESULTS: By
      embryonic day 18 and postnatal day 0, lymphatics were already observed in the
      submesothelial connective tissue on the peritoneal side of the fetal diaphragm.
      The lymphatic endothelial cells, but not the mesothelial cells covering the
      diaphragm, protruded short cytoplasmic processes into the submesothelial
      connective tissue, and these almost reached the basal surfaces of individual
      mesothelial cells. By postnatal days 4 and 10, the lymphatic endothelial cells
      frequently protruded cytoplasmic processes into the submesothelial connective
      tissue, and the endothelial cell processes broke the continuity of both the basal
      lamina beneath the mesothelial cells and the submesothelial connective tissue.
      Neighboring endothelial processes formed a pair of U-shaped folds that were
      connected with each other via intercellular junctions at the apexes of the U
      shaped folds. The disassembly of the intercellular junctions between the U-shaped
      folds was observed, and the basal surface of the mesothelial cell faced the
      lymphatic lumen. Dehiscence of the intercellular junctions between the
      mesothelial cells overlaying the lymphatics was observed, and lymphatic stomata
      were present. On the pleural side of the diaphragm, lymphatics were already
      present on embryonic day 18, but it was not observed that the endothelial process
      spanned the submesothelial connective tissue to the basal surface of the
      mesothelial cell. CONCLUSIONS: These results suggest the following process of the
      formation of the lymphatic stomata. (1) Neighboring lymphatic endothelial cells
      span the submesothelial connective tissue to the basal surfaces of mesothelial
      cells. (2) The lymphatic stomata are formed by the disassembly of the
      intercellular junctions between the neighboring endothelial cells and between the
      mesothelial cells overlying the endothelial cells.

PMID- 9143678
TI  - Anatomical study of the abdominal arterial system in soricids (Insectivora,
      Mammalia): functional and phylogenetic implications.
AB  - BACKGROUND: Information on the anatomy of the abdominal arterial system in
      Insectivora is scarce. We described the origin, distribution, and variations of
      the visceral abdominal arteries in some Soricidae in order to provide the first
      comprehensive data on this subject in Insectivora. Results were interpreted from
      a functional and phylogenetic viewpoint. METHODS: The sample examined consisted
      of 46 shrews (25 Crocidura russula, 12 Sorex araneus, 5 S. coronatus, 4 S.
      minutus) captured in the field. Animals were analyzed by injection of coloured
      latex solution through the left ventricle of the heart and subsequent dissection.
      RESULTS: The coeliacomesenteric trunk was the first visceral branch of the
      abdominal aorta. The cranial mesenteric artery supplied those parts of the
      digestive tract attached to the cranial mesentery and usually gave rise to the
      colic, the caudal pancreaticoduodenal, and the jejunum-ileumcolic arteries. The
      coeliac artery mainly vascularized the stomach, the liver and the first portion
      of the duodenum, and the spleen by means of several branches of the left gastric,
      the "common" hepatic, and the lienal arteries, respectively. The lienal arteries
      were double. The renal, gonadal, and median sacral arteries were also branches of
      the abdominal aorta. The caudal mesenteric artery emerged either from the
      abdominal aorta or from one of the common iliac arteries. CONCLUSIONS:
      Differences in the abdominal blood supply between soricids and more advanced
      mammals are basically focused on the irrigation of the digestive tract. The
      presence of double lienal arteries and the absence of right gastric artery and
      left and right gastroepiploic arteries are related to the primitive type of gut
      presented in the order and are thought to be the plesiomorphic condition in
      Eutheria.

PMID- 9143677
TI  - Quantitative morphological changes in neurons from the dorsal lateral geniculate
      nucleus of young and old rats.
AB  - BACKGROUND: We studied the morphological changes occurring in neurons from the
      dorsal lateral geniculate nucleus (dLGN) during aging by analysing the size and
      shape of cell bodies and nuclei. METHODS: Male albino Wistar rats, aged 3, 18,
      24, and 30 months, were used. After appropriate tissue preparation and following
      the usual histological procedure, the profiles of 1,920 neuronal bodies and
      nuclei were drawn using a camera lucida. Data was later recorded and processed
      with a semiautomatic image analyser. RESULTS AND CONCLUSIONS: We observed that
      dLGN neurons do not change in size from the age of 3-24 months. Between 24 and 30
      months, the soma and nucleus of the cell undergo hypertrophy, 32.8% and 35.6%,
      respectively, when compared to those from 3-month-old animals (P < 0.01).
      Furthermore, we found a high correlation between cell body size/nucleus size,
      which does not disappear with age. The r values (correlation coefficient) were
      0.7998, 0.8662, 0.8433 and 0.7304, and R2 (determination coefficient) was equal
      to 0.6397, 0.7504, 0.7112, and 0.5335. These latter values show that in 63.97%,
      75.04%, 71.12%, and 53.35% of cases, respectively, modifications in somata size
      were accompanied by similar changes in nucleus size, and vice-versa. The study of
      the shape of the soma and nucleus of the cell revealed that both structures have
      a rounded-oval configuration that does not change in a significant way from
      adulthood to old age.

PMID- 9143679
TI  - The immune system as a supersystem.
AB  - I coined a term "supersystem" to designate highly integrated life systems such as
      the immune system, nervous system, and embryogenesis. While the mechanistic
      system is defined as a set of diverse elements so connected and related as to
      form an organic whole for a particular purpose, the "supersystem" engenders its
      own elements from a single progenitor. The diverse elements thus generated form
      relationship by mutual adaptation and coadaptation, and thus they create a
      dynamic self-regulating system through self-organization. It is a closed self
      satisfied system, yet open to the environment, receiving outside signals to
      transduce them into internal messages for self-regulation and expansion. Unlike a
      mechanistic system, the "supersystem" has no defined purpose and determines its
      own fate by referring to its self-established behavioral pattern. Both the immune
      and nervous systems develop and function as a typical "supersystem." The
      prototype of the supersystem can be seen in embryogenesis and evolution. The
      concept of the supersystem can also be applied to the development of language, or
      a city, or other cultural phenomena that human beings have created as a result of
      their vital activities.

PMID- 9143680
TI  - Human T cell leukemia virus type I (HTLV-I) and human diseases.
AB  - HTLV-I infection is causally associated with a variety of human diseases
      including leukemia/lymphoma, myelopathy, uveitis, and arthropathy. Tax protein of
      HTLV-I, which is considered oncogenic, binds to transcription factors or other
      cytoplasmic cellular molecules involved in the fundamental cell function and
      thereby induces cellular changes. The interaction between HTLV-I-infected cells
      with dysregulated function and different kinds of cells in the host, such as
      lymphocytes and vascular endothelial cells through viral peptides, antigen
      receptors cell adhesion molecules, and cytokines, appears to be one of the basic
      mechanisms underlying the development of HTLV-I-associated diseases. This
      interaction may play a major role in determining tumorigenicity and in forming
      clinical features of the diseases. The in vivo cell proliferation model of HTLV-I
      infected cells using severe combined immunodeficient (SCID) mice can
      differentiate tumorigenicity from cell immortalization in vitro. The OX40 and its
      ligand gp34, which are induced by HTLV-I infection and directly mediate the
      adhesion between HTLV-I-infected T cells and vascular endothelial cells, may be
      critically involved in the localization and proliferation of HTLV-I-infected
      cells in vivo.

PMID- 9143681
TI  - The male-specific histocompatibility antigen, H-Y: a history of transplantation,
      immune response genes, sex determination and expression cloning.
AB  - H-Y was originally discovered as a transplantation antigen. In vivo primary skin
      graft responses to H-Y are controlled by immune response (Ir) genes mapping to
      the MHC. In vitro T cell responses to H-Y are controlled by MHC class I and II Ir
      genes, which-respectively, restrict CD8 and CD4 T cells: These can be isolated as
      T cell clones in vitro. T cell receptor (TCR) transgenic mice have been made from
      the rearranged TCR genes of several of these, of which that specific for H-Y/Db
      is the best studied. Non-MHC Ir genes also contribute to the control of in vitro
      CTL responses to H-Y. The Hya/HYA gene(s) encoding H-Y antigen have been mapped
      using translocations, mutations, and deletions to Yq in humans and to the short
      arm of the Y chromosome in mice, where they lie in the deletion defined by the
      Sxrb mutation between Zfy-1 and Zfy-2. Hya/HYA has been separated from the testis
      determining gene, Sry/SRY, in both humans and mice and in humans the azoospermia
      factor AZF has been separated from HYA. In mice transfection of cosmids and cDNAs
      mapping to the Sxrb deletion has identified two genes encoding H-Y peptide
      epitopes. Two such epitopes, H-Y/K(k) and H-Y/D(k), are encoded within different
      exons of Smcy and a third, H-Y/D(b), by a novel gene, Uty. Peptide elution
      approaches have isolated a human H-Y epitope, H-Y/HLA-B7, and identified it as a
      product of SMCY. Each of the Hya genes in mice is ubiquitously expressed but of
      unknown function. Their X chromosome homologues do not undergo X inactivation.

PMID- 9143682
TI  - Lyme disease: a review of aspects of its immunology and immunopathogenesis.
AB  - Lyme disease, caused by Borrelia burgdorferi, causes a multisystem inflammatory
      ailment, although the precise means of tissue damage are not well understood. It
      is clear that the organism is present at the site of inflammation in many organs
      and that many of the features of the illness are relieved by antibiotic therapy.
      A complex interaction between spirochete and immune systems of a number of
      mammalian hosts, in human disease and animal models, has been described. It is
      clear that T cells and macrophages are intimately associated with the
      pathogenesis of arthritis and that immune mechanisms are involved in other
      aspects of disease. Inflammation directed at persistence of Borrelial antigens is
      a plausible explanation for persisting arthritis. Autoimmunity based on molecular
      mimicry may play a role in the pathogenesis of Lyme disease. Humoral immunity
      plays a protective role, prompting interest in vaccine development. Significant
      variation in certain of the outer surface proteins suggests that multiple
      proteins, peptides, or chimeric vaccines may be needed to provide a sufficiently
      broad humoral protective response.

PMID- 9143683
TI  - Naturally occurring primary deficiencies of the immune system.
AB  - Naturally occurring genetic disorders of the immune system provide many models
      for the study of its development and function. In a way, their analysis
      complements the information provided by the generation of genetic defects in mice
      created using homologous recombination techniques. In this review, the recent
      findings made in three areas are focused upon deficiencies in T cell
      differentiation and in T lymphocyte activation, and on the control process of
      peripheral immune response.

PMID- 9143684
TI  - Differential signaling by lymphocyte antigen receptors.
AB  - Studies performed during the past several years make plain that ligand occupancy
      of antigen receptors need not necessarily provoke identical responses in all
      instances. For example, ligation of antigen receptors may stimulate a
      proliferative response, induce a state of unresponsiveness to subsequent
      stimulation (anergy), or induce apoptosis. How does a single type of
      transmembrane receptor induce these very heterogeneous cellular responses? In the
      following pages, we outline evidence supporting the view that the nature of the
      ligand/receptor interaction directs the physical recruitment of signaling
      pathways differentially inside the lymphocyte and hence defines the nature of the
      subsequent immune response. We begin by providing a functional categorization of
      antigen receptor components, considering the ways in which these components
      interact with the known set of signal transduction pathways, and then review the
      evidence suggesting that differential signaling through the TCR is achieved by
      qualitative differences in the effector pathways recruited by TCR, perhaps
      reflecting the time required to bring complicated signal transduction elements
      into proximity within the cell. The time-constant of the interaction between
      antigen and receptor in this way determines, at least in part, the nature of the
      resulting response. Finally, although our review focuses substantially on T cell
      receptor signaling, we have included a less detailed description of B cell
      receptor signaling as well, simply to emphasize the parallels that exist in these
      two closely related systems.

PMID- 9143685
TI  - The role of the Ikaros gene in lymphocyte development and homeostasis.
AB  - The Ikaros gene, which encodes a family of hemopoietic-specific zinc finger
      proteins, is described as a central regulator of lymphocyte differentiation.
      During fetal development, it is required at the earliest stage of T cell and B
      cell specification. In the adult, however, lymphoid lineages rely on Ikaros at
      distinct phases of their development. Its activity is essential for the
      generation of B cell but not of T cell precursors, although the differentiation
      of the latter is not normal. A significant increase in CD4 thymocytes and their
      immediate precursors is detected, and because these cells lack markers that
      correlate with positive selection, a deregulation in their maturation process is
      suggested. Furthermore, Ikaros-null thymocytes hyperproliferate in response to T
      cell receptor (TCR) signaling; within days after their appearance in the thymus,
      clonally expanding populations are detected. Deregulated TCR-mediated responses
      and the fast kinetics of tumor development in these mutant thymocytes implicate
      Ikaros as a central tumor suppressor gene for the T cell lineage. In addition,
      lack of natural killer cells and selective defects in gamma delta T cells and
      dendritic antigen-presenting cells point to Ikaros as an essential factor for the
      establishment of early branchpoints of the T cell pathway. The dominant
      interference activity of Ikaros isoforms unable to bind DNA and their effects in
      lymphocyte development suggest that Ikaros works in concert with other factors.
      The role of Aiolos, a lymphoid-restricted and structurally related gene, in
      lymphoid differentiation is discussed. A model is proposed that defines Ikaros as
      the backbone of a complex regulatory protein network that controls cell fate
      decisions and regulates homeostasis in the hemo-lymphoid system. Changes in this
      regulatory network may reflect differentiation and proliferation adjustments made
      in hemo-lymphoid progenitors and precursors as they give rise to the cells of our
      immune system.

PMID- 9143686
TI  - The genetic defect in ataxia-telangiectasia.
AB  - The autosomal recessive human disorder ataxia-telangiectasia (A-T) was first
      described as a separate disease entity 40 years ago. It is a multisystem disease
      characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia,
      radiosensitivity, predisposition to lymphoid malignancies and immunodeficiency,
      with defects in both cellular and humoral immunity. The pleiotropic nature of the
      clinical and cellular phenotype suggests that the gene product involved is
      important in maintaining stability of the genome but also plays a more general
      role in signal transduction. The chromosomal instability and radiosensitivity so
      characteristic of this disease appear to be related to defective activation of
      cell cycle checkpoints. Greater insight into the nature of the defect in A-T has
      been provided by the recent identification, by positional cloning, of the
      responsible gene, ATM. The ATM gene is related to a family of genes involved in
      cellular responses to DNA damage and/or cell cycle control. These genes encode
      large proteins containing a phosphatidylinositol 3-kinase domain, some of which
      have protein kinase activity. The mutations causing A-T completely inactivate or
      eliminate the ATM protein. This protein has been detected and localized to
      different subcellular compartments.

PMID- 9143687
TI  - Fc receptor biology.
AB  - This review deals with membrane Fc receptors (FcR) of the immunoglobulin
      superfamily. It is focused on the mechanisms by which FcR trigger and regulate
      biological responses of cells on which they are expressed. FcR deliver signals
      when they are aggregated at the cell surface. The aggregation of FcR having
      immunoreceptor tyrosine-based activation motifs (ITAMs) activates sequentially
      src family tyrosine kinases and syk family tyrosine kinases that connect
      transduced signals to common activation pathways shared with other receptors. FcR
      with ITAMs elicit cell activation, endocytosis, and phagocytosis. The nature of
      responses depends primarily on the cell type. The aggregation of FcR without ITAM
      does not trigger cell activation. Most of these FcR internalize their ligands,
      which can be endocytosed, phagocytosed, or transcytosed. The fate of internalized
      receptor-ligand complexes depends on defined sequences in the intracytoplasmic
      domain of the receptors. The coaggregation of different FcR results in positive
      or negative cooperation. Some FcR without ITAM use FcR with ITAM as signal
      transduction subunits. The coaggregation of antigen receptors or of FcR having
      ITAMs with FcR having immunoreceptor tyrosine-based inhibition motifs (ITIMs)
      negatively regulates cell activation. FcR therefore appear as the subunits of
      multichain receptors whose constitution is not predetermined and which deliver
      adaptative messages as a function of the environment.

PMID- 9143688
TI  - Neutralizing antiviral B cell responses.
AB  - Neutralizing antiviral B cell responses differ in various aspects from the many
      usually measured B cell responses specific for protein in adjuvants. In
      particular, such neutralizing antiviral B cell responses are more rapidly
      induced, reach higher titers, are longer lived, and are efficiently generated
      without adjuvants. Evidence is summarized here that the repetitiveness of many
      viral antigens is a key factor responsible for the efficiency of these B cell
      responses, amplifying B cells early and rapidly for potent IgM responses and also
      for efficient switching to IgG. The data reviewed indicate that B cells
      discriminate antigen patterns via the degree of surface Ig-cross-linking and use
      antigen repetitiveness as a self/nonself discriminator.

PMID- 9143689
TI  - Escape of human immunodeficiency virus from immune control.
AB  - Cytotoxic T lymphocytes (CTL) play a crucial role in the attempt to control
      infection with human immunodeficiency virus (HIV). Variation in epitopes
      recognized by CTL is common and frequently offers potential escape routes for
      mutant virus. Proof of escape, however, requires demonstration of increased
      frequency of virus particles or provirus that carry the escape sequence. There
      are now several recorded examples of virus variants that escape from CTL and are
      then selected. Most dramatic are those in which the CTL response has been
      dominated by CTL recognizing a single epitope that has suddenly changed,
      resulting in escape to fixation. This has been seen both early and late in the
      infection, leaving no doubt that escape occurs. Such escape is likely to be
      favored when the antiviral CTL response is oligoclonal and focused on a small
      number of immunodominant epitopes. The heterogeneous CTL response seen in many
      HIV-infected patients may result from successive waves of virus escape followed
      by new CTL responses specific for subdominant epitopes. Mutant virus can escape
      by several different routes, including failure of the mutated peptide to bind to
      the presenting HLA molecule and altered interactions with T cell receptors (TCR),
      including antagonism.

PMID- 9143690
TI  - Induction of Th1 and Th2 CD4+ T cell responses: the alternative approaches.
AB  - T helper lymphocytes can be divided into two distinct subsets of effector cells
      based on their functional capabilities and the profile of cytokines they produce.
      The Th1 subset of CD4+ T cells secretes cytokines usually associated with
      inflammation, such as IFN-gamma and TNF and induces cell-mediated immune
      responses. The Th2 subset produces cytokines such as IL-4 and IL-5 that help B
      cells to proliferate and differentiate and is associated with humoral-type immune
      responses. The selective differentiation of either subset is established during
      priming and can be significantly influenced by a variety of factors. One of these
      factors, the cytokine environment, has been put forward as the major variable
      influencing Th development and is already well reviewed by others. Instead, in
      the current review, we focus on some of the alternative approaches for skewing
      Th1/Th2 responses. Specifically, we discuss the effects on Th priming of (a)
      using altered peptide ligands as antigens, (b) varying the dose of antigen, and
      (c) altering costimulatory signals. The potential importance of each of these
      variables to influence immune responses to pathogens in vivo is discussed
      throughout.

PMID- 9143691
TI  - Nitric oxide and macrophage function.
AB  - At the interface between the innate and adaptive immune systems lies the high
      output isoform of nitric oxide synthase (NOS2 or iNOS). This remarkable molecular
      machine requires at least 17 binding reactions to assemble a functional dimer.
      Sustained catalysis results from the ability of NOS2 to attach calmodulin without
      dependence on elevated Ca2+. Expression of NOS2 in macrophages is controlled by
      cytokines and microbial products, primarily by transcriptional induction. NOS2
      has been documented in macrophages from human, horse, cow, goat, sheep, rat,
      mouse, and chicken. Human NOS2 is most readily observed in monocytes or
      macrophages from patients with infectious or inflammatory diseases. Sustained
      production of NO endows macrophages with cytostatic or cytotoxic activity against
      viruses, bacteria, fungi, protozoa, helminths, and tumor cells. The antimicrobial
      and cytotoxic actions of NO are enhanced by other macrophage products such as
      acid, glutathione, cysteine, hydrogen peroxide, or superoxide. Although the high
      output NO pathway probably evolved to protect the host from infection,
      suppressive effects on lymphocyte proliferation and damage to other normal host
      cells confer upon NOS2 the same protective/destructive duality inherent in every
      other major component of the immune response.

PMID- 9143692
TI  - Redox regulation of cellular activation.
AB  - Growing evidence has indicated that cellular reduction/oxidation (redox) status
      regulates various aspects of cellular function. Oxidative stress can elicit
      positive responses such as cellular proliferation or activation, as well as
      negative responses such as growth inhibition or cell death. Cellular redox status
      is maintained by intracellular redox-regulating molecules, including thioredoxin
      (TRX). TRX is a small multifunctional protein that has a redox-active
      disulfide/dithiol within the conserved active site sequence: Cys-Gly-Pro-Cys.
      Adult T cell leukemia-derived factor (ADF), which we originally defined as an IL
      2 receptor alpha-chain/Tac inducer produced by human T cell lymphotrophic virus-I
      (HTLV-I)-transformed T cells, has been identified as human TRX. TRX/ADF is a
      stress-inducible protein secreted from cells. TRX/ADF has both intracellular and
      extracellular functions as one of the key regulators of signaling in the cellular
      responses against various stresses. Extracellularly, TRX/ADF shows a
      cytoprotective activity against oxidative stress-induced apoptosis and a growth
      promoting effect as an autocrine growth factor. Intracellularly, TRX/ADF is
      involved in the regulation of protein-protein or protein-nucleic acid
      interactions through the reduction/oxidation of protein cysteine residues. For
      example, TRX/ADF translocates from the cytosol into the nucleus by a variety of
      cellular stresses, to regulate the expression of various genes through the redox
      factor-1 (Ref-1)/APEX. Further studies to clarify the regulatory roles of TRX/ADF
      and its target molecules may elucidate the intracellular signaling pathways in
      the responses against various stresses. The concept of "redox regulation" is
      emerging as an understanding of the novel mechanisms in the pathogenesis of
      several disorders, including viral infections, immunodeficiency, malignant
      transformation, and degenerative disease.

PMID- 9143693
TI  - Leukocyte protein tyrosine kinases: potential targets for drug discovery.
AB  - Intracellular signal transduction following the extracellular ligation of a wide
      variety of different types of surface molecules on leukocytes involves the
      activation of protein tyrosine kinases. The dependence of successful
      intracellular signaling on the functions of the nontransmembrane class of protein
      tyrosine kinases coupled with the cell type-specific expression patterns for
      several of these enzymes makes them appealing targets for therapeutic
      intervention. Development of drugs that can interfere with the catalytic
      functions of the nontransmembrane protein tyrosine kinases or that can disrupt
      critical interactions with regulatory molecules and/or substrates should find
      clinical applications in the treatment of allergic diseases, autoimmunity,
      transplantation rejection, and cancer.

PMID- 9143694
TI  - Human cytotoxic T lymphocyte responses to Epstein-Barr virus infection.
AB  - Epstein-Barr virus (EBV) provides one of the most informative systems with which
      to study cytotoxic T lymphocyte (CTL) responses in humans. The virus establishes
      a highly immunogenic growth-transforming infection of B lymphocytes, associated
      with the coordinate expression of six virus-coded nuclear antigens (EBNAs 1, 2,
      3A, 3B, 3C, -LP) and two latent membrane proteins (LMPs 1 and 2). This elicits
      both primary and memory CT8+ CTL responses that are markedly skewed toward HLA
      allele-specific epitopes drawn from the EBNA3A, 3B, 3C subset of latent proteins,
      with reactivities to other antigens being generally much less frequent. This
      hierarchy of immunodominance among the different latent proteins may at least
      partly reflect their differential accessibility to the HLA class I-processing
      pathway. Furthermore, CTLs to some of the immunodominant epitopes involve highly
      conserved T cell receptor (TCR) usage, a level of focusing which evidence
      suggests could have immunopathological consequences from cross-reactive
      recognition of other target structures. EBV is associated with a range of human
      tumors, and there is increasing interest in the possibility of targeting such
      malignancies using virus-specific CTLs. The dramatic reversal of EBV-driven
      lymphoproliferations in bone marrow transplant patients following CTL infusion
      demonstrates the potential of this approach, and here we discuss prospects for
      its extension to other EBV-positive tumors in which the immunodominant EBNA3A,
      3B, 3C proteins are not expressed.

PMID- 9143696
TI  - Initiation and processing of signals from the B cell antigen receptor.
AB  - Current models of signal transduction from the antigen receptors on B and T cells
      still resemble equations with several unknown elements. Data from recent knockout
      experiments in cell lines and mice contradict the assumption that Src-family
      kinase and tyrosine kinases of the Syk/Zap-70 family are the transducer elements
      that set signaling from these receptors in motion. Using a functional definition
      of signaling elements, we discuss the current knowledge of signaling events from
      the BCR and suggest the existence of an as-yet-unknown BCR transducer complex.

PMID- 9143695
TI  - Structure and function of the pre-T cell receptor.
AB  - The pre-T cell receptor (pre-TCR) that minimally consists of the TCR beta chain
      and the disulfide-linked pre-T cell receptor alpha (pT alpha) chain in
      association with signal-transducing CD3 molecules rescues from programmed cell
      death cells with productive TCR beta rearrangements. The pre-TCR induces
      expansion and differentiation of these cells such that they become TCR alpha beta
      bearing CD4+8+ thymocytes, which express only a single TCR beta chain and then
      either die of neglect or--upon TCR-ligand interaction--undergo either positive or
      negative selection. The newly discovered pT alpha gene encodes a transmembrane
      protein that belongs to the Ig superfamily and contains a cytoplasmic tail that,
      however, has no essential function in signal transduction, which is mediated by
      CD3 molecules and most likely p56lck. Experiments in pT alpha gene-deficient mice
      show that the pre-TCR has a crucial role in maturation as well as allelic
      exclusion of alpha beta T cells but is not required for the development of gamma
      delta-expressing cells. The function of the pre-TCR cannot be fully assumed by an
      alpha beta TCR that is expressed abnormally early in T cell development.

PMID- 9143697
TI  - CD22, a B lymphocyte-specific adhesion molecule that regulates antigen receptor
      signaling.
AB  - The development of B lymphocytes is a highly regulated process that depends in
      part on lineage-specific cell surface molecules. In addition, transmembrane
      signals generated through the B cell antigen receptor and other surface molecules
      regulate B cell responses to foreign antigens. Recent studies reveal CD22 to be a
      functionally significant receptor during these processes. CD22 is first expressed
      in the cytoplasm of pro-B and pre-B cells, and on the surface as B cells mature
      to become IgD+. CD22 is a member of the Ig superfamily that serves as an adhesion
      receptor for sialic acid-bearing ligands expressed on erythrocytes and all
      leukocyte classes. In addition to its potential role as a mediator of
      intercellular interactions, signal transduction through CD22 can activate B cells
      and modulate antigen receptor signaling in vitro. CD22 signaling is mediated via
      interactions with a number of kinases and phosphatases that bind the cytoplasmic
      domain through phosphorylated tyrosine residues located within consensus TAM and
      TIM motifs. The phenotype of CD22-deficient mice suggests that CD22 is primarily
      involved in the generation of mature B cells within the bone marrow, blood, and
      marginal zones of lymphoid tissues. Most notable in CD22-deficient mice is a
      significant diminution of surface Ig levels in these B cell subpopulations, which
      suggests that CD22 functions in vivo to adjust the signaling threshold of cell
      surface antigen receptors. A further understanding of CD22 function is required
      and may reveal roles for CD22 in disease susceptibility or the development of
      autoimmunity.

PMID- 9143698
TI  - Cytokine regulation of host defense against parasitic gastrointestinal nematodes:
      lessons from studies with rodent models.
AB  - Studies with rodents infected with Trichinella spiralis, Heligmosomoides
      polygyrus, Nippostronglyus brasiliensis, and Trichuris muris have provided
      considerable information about immune mechanisms that protect against parasitic
      gastrointestinal nematodes. Four generalizations can be made: 1. CD4+ T cells are
      critical for host protection; 2. IL-12 and IFN-gamma inhibit protective immunity;
      3. IL-4 can: (a) be required for host protection, (b) limit severity of
      infection, or (c) induce redundant protective mechanisms; and 4. Some cytokines
      that are stereotypically produced in response to gastrointestinal nematode
      infections fail to enhance host protection against some of the parasites that
      elicit their production. Host protection is redundant at two levels: 1. IL-4 has
      multiple effects on the immune system and on gut physiology (discussed in this
      review), more than one of which may protect against a particular parasite; and 2.
      IL-4 is often only one of multiple stimuli that can induce protection. Hosts may
      have evolved the ability to recognize features that characterize parasitic
      gastrointestinal nematodes as a class as triggers for a stereotypic cytokine
      response, but not the ability to distinguish features of individual parasites as
      stimuli for more specific protective cytokine responses. As a result, hosts
      deploy a set of defense mechanisms against these parasites that together control
      infection by most members of that class, even though a specific defense mechanism
      may not be required to defend against a particular parasite and may even damage a
      host infected with that parasite.

PMID- 9143699
TI  - Mouse CD1-specific NK1 T cells: development, specificity, and function.
AB  - NK1 T cells are a specialized population of alpha/beta T cells that coexpress
      receptors of the NK lineage and have the unique potential to very rapidly secrete
      large amounts of cytokines, providing early help for effector cells and
      regulating the Th1 or Th2 differentiation of some immune responses. NK1 T cells
      express a restricted TCR repertoire made of an invariant TCR alpha chain, V alpha
      14-J alpha 281, associated with polyclonal V beta 8, V beta 7, and V beta 2 TCR
      beta chains. NK1 T cells recognize the products of the conserved family of MHC
      class I-like CD1 genes, apparently in the absence of foreign antigens. Thus, this
      novel regulatory pathway, which straddles the innate and the adaptive immune
      systems, is unique in that its activation may not require associative recognition
      of antigen. Here, we review the specificity and function of mouse NK1 T cells,
      and we discuss the relationship of this lineage to mainstream T cells and NK
      cells.

PMID- 9143700
TI  - The IFN gamma receptor: a paradigm for cytokine receptor signaling.
AB  - During the last several years, the mechanism of IFN gamma-dependent signal
      transduction has been the focus of intense investigation. This research has
      recently culminated in the elucidation of a comprehensive molecular understanding
      of the events that underlie IFN gamma-induced cellular responses. The structure
      and function of the IFN gamma receptor have been defined. The mechanism of IFN
      gamma signal transduction has been largely elucidated, and the physiologic
      relevance of this process validated. Most recently, the molecular events that
      link receptor ligation to signal transduction have been established. Together
      these insights have produced a model of IFN gamma signaling that is nearly
      complete and that serves as a paradigm for signaling by other members of the
      cytokine receptor superfamily.

PMID- 9143701
TI  - Bone marrow-derived dendritic cells, infection with human immunodeficiency virus,
      and immunopathology.
AB  - Dendritic cells (DC) exposed to HIV-1 show nonproductive infection that may
      become productive as they mature. The distribution of DC within genital mucosa
      and their susceptibility to infection particularly with clade E viruses could be
      reflected in the ease of heterosexual transmission. Carriage of virus and viral
      antigen by DC into lymph nodes may allow clustering and activation of T cells and
      production of protective immune responses. However, secondary infection of
      activated T cells from infected DC could cause dissemination of virus and loss of
      infected DC and T cells. In asymptomatic infection, fewer dendritic cells with
      reduced capacity to stimulate CD4 T cell proliferation are found before evidence
      of T cell abnormalities, and these early changes in antigen-presenting cells may
      result in a decline in the production of CD4 memory T cells. However, DC fuel
      ongoing production of antibody to HIV-1. Signaling by DC to T cells may thus
      underlie two major features of early HIV infection--loss in CD4+ memory T cells
      and persistence of antibody production. In AIDS, infected dendritic and
      epithelial cells within the thymus may affect maturation and contribute to loss
      of the "naive" T cell population. Further loss of memory T cells may occur
      through syncytium formation with infected DC. Finally, in AIDS patients, there is
      a failure in the development and the function of DC from CD34+ stem cells. In
      conclusion, the infection of dendritic cells, loss in their numbers, and changed
      signaling to T cells may shape the pattern of immunity during infection with HIV
      1. Conversely, treatments that reverse the defect in antigen presentation by DC
      may improve cell-mediated immunity.

PMID- 9143702
TI  - DNA vaccines.
AB  - Observations in the early 1990s that plasmid DNA could directly transfect animal
      cells in vivo sparked exploration of the use of DNA plasmids to induce immune
      responses by direct injection into animals of DNA encoding antigenic proteins.
      This method, termed DNA immunization, now has been used to elicit protective
      antibody and cell-mediated immune responses in a wide variety of preclinical
      animal models for viral, bacterial, and parasitic diseases. DNA vaccination is
      particularly useful for the induction of cytotoxic T cells. This review
      summarizes current knowledge on the vectors, immune responses, immunological
      mechanisms, safety considerations, and potential for further application of this
      novel method of immunization.

PMID- 9143703
TI  - Role of complement in HIV infection.
AB  - In human plasma, HIV activates the complement system, even in the absence of
      specific antibodies. Complement activation would, however, be harmful to the
      virus if the reactions were allowed to go to completion, since their final
      outcome would be virolysis. This is avoided by complement regulatory molecules,
      which either are included in the virus membrane upon budding from the infected
      cells (e.g. DAF/CD55) or are secondarily attached to HIV envelope glycoproteins
      as in the case of factor H. By using this strategy of interaction with complement
      components, HIV takes advantage of human complement activation for enhancement of
      infectivity, for follicular localization, and for broadening its target cell
      range at the same time that it displays an intrinsic resistance against the lytic
      action of human complement. This intrinsic resistance to complement-mediated
      virolysis can be overcome by monoclonal antibodies inhibiting recruitment of
      human factor H to the virus surface, suggesting a new therapeutic principle.

PMID- 9143704
TI  - Human chemokines: an update.
AB  - Interleukin 8, the first chemokine to be characterized, was discovered nearly ten
      years ago. Today, more than 30 human chemokines are known. They are often
      upregulated in inflammation and act mainly on leukocytes inducing migration and
      release responses. The present review deals largely with the new developments of
      the last three years. Several structural studies have shown that most chemokines
      form dimers. The dimers, however, dissociate upon dilution, and the monomers
      constitute the biologically active form. Chemokine activities are mediated by
      seven-transmembrane-domain, G protein coupled receptors, five of which were
      discovered in the past three years. The primary receptor-binding domain of all
      chemokines is near the NH2 terminus, and antagonists can be obtained by
      truncation or substitutions in this region. Major progress has been made in the
      understanding of chemokine actions on T lymphocytes that respond to several CC
      chemokines but also to IP10 and Mig, two CXC chemokines that selectively attract
      T cells via a novel receptor. Effects of chemokines on angiogenesis and tumor
      growth have been reported, but the data are still contradictory and the
      mechanisms unknown. Of considerable interest is the recent discovery that some
      chemokines function as HIV-suppressive factors by interacting with chemokine
      receptors which, together with CD4, were recognized as the binding sites for HIV
      1.

PMID- 9143705
TI  - Transcription factors of the NFAT family: regulation and function.
AB  - As targets for the immunosuppressive drugs cyclosporin A and FK506, transcription
      factors of the NFAT (nuclear factor of activated T cells) family have been the
      focus of much attention. NFAT proteins, which are expressed in most immune-system
      cells, play a pivotal role in the transcription of cytokine genes and other genes
      critical for the immune response. The activity of NFAT proteins is tightly
      regulated by the calcium/calmodulin-dependent phosphatase calcineurin, a primary
      target for inhibition by cyclosporin A and FK506. Calcineurin controls the
      translocation of NFAT proteins from the cytoplasm to the nucleus of activated
      cells by interacting with an N-terminal regulatory domain conserved in the NFAT
      family. The DNA-binding domains of NFAT proteins resemble those of Rel-family
      proteins, and Rel and NFAT proteins show some overlap in their ability to bind to
      certain regulatory elements in cytokine genes. NFAT is also notable for its
      ability to bind cooperatively with transcription factors of the AP-1 (Fos/Jun)
      family to composite NFAT:AP-1 sites, found in the regulatory regions of many
      genes that are inducibly transcribed by immune-system cells. This review
      discusses recent data on the diversity of the NFAT family of transcription
      factors, the regulation of NFAT proteins within cells, and the cooperation of
      NFAT proteins with other transcription factors to regulate the expression of
      inducible genes.

PMID- 9143706
TI  - Cellular responses to interferon-gamma.
AB  - Interferons are cytokines that play a complex and central role in the resistance
      of mammalian hosts to pathogens. Type I interferon (IFN-alpha and IFN-beta) is
      secreted by virus-infected cells. Immune, type II, or gamma-interferon (IFN
      gamma) is secreted by thymus-derived (T) cells under certain conditions of
      activation and by natural killer (NK) cells. Although originally defined as an
      agent with direct antiviral activity, the properties of IFN-gamma include
      regulation of several aspects of the immune response, stimulation of bactericidal
      activity of phagocytes, stimulation of antigen presentation through class I and
      class II major histocompatibility complex (MHC) molecules, orchestration of
      leukocyte-endothelium interactions, effects on cell proliferation and apoptosis,
      as well as the stimulation and repression of a variety of genes whose functional
      significance remains obscure. The implementation of such a variety of effects by
      a single cytokine is achieved by complex patterns of cell-specific gene
      regulation: Several IFN-gamma-regulated genes are themselves components of
      transcription factors. The IFN-gamma response is itself regulated by interaction
      with responses to other cytokines including IFN-alpha/beta, TNF-alpha, and IL-4.
      Over 200 genes are now known to be regulated by IFN-gamma and they are listed in
      a World Wide Web document that accompanies this review. However, much of the
      cellular response to IFN-gamma can be described in terms of a set of integrated
      molecular programs underlying well-defined physiological systems, for example the
      induction of efficient antigen processing for MHC-mediated antigen presentation,
      which play clearly defined roles in pathogen resistance. A promising approach to
      the complexity of the IFN-gamma response is to extend the analysis of the less
      understood IFN-gamma-regulated genes in terms of molecular programs functional in
      pathogen resistance.

PMID- 9143707
TI  - Gp130 and the interleukin-6 family of cytokines.
AB  - Receptors for most interleukins and cytokines that regulate immune and
      hematopoietic systems belong to the class I cytokine receptor family. These
      molecules form multichain receptor complexes in order to exhibit high-affinity
      binding to, and mediate biological functions of, their respective cytokines. In
      most cases, these functional receptor complexes share common signal transducing
      receptor components that are also in the class I cytokine receptor family, i.e.
      gp130, common beta, and common gamma molecules. Interleukin-6 and related
      cytokines, interleukin-11, leukemia inhibitory factor, oncostatin M, ciliary
      neurotrophic factor, and cardiotrophin-1 are all pleiotropic and exhibit
      overlapping biological functions. Functional receptor complexes for this
      interleukin-6 family of cytokines share gp130 as a component critical for signal
      transduction. Unlike cytokines sharing common beta and common gamma chains that
      mainly function in hematopoietic and lymphoid cell systems, the interleukin-6
      family of cytokines function extensively outside these systems as well, e.g. from
      the cardiovascular to the nervous system, owing to ubiquitously expressed gp130.
      Stimulation of cells with the interleukin-6 family of cytokines triggers homo- or
      hetero-dimerization of gp130. Although gp130 and its dimer partners possess no
      intrinsic tyrosine kinase domain, the dimerization of gp130 leads to activation
      of associated cytoplasmic tyrosine kinases and subsequent modification of
      transcription factors. This paper reviews recent progress in the study of the
      interleukin-6 family of cytokines and gp130.

PMID- 9143708
TI  - Capture and processing of exogenous antigens for presentation on MHC molecules.
AB  - Class I and class II MHC molecules bind peptides during their biosynthetic
      maturation and provide a continuously updated display of intracellular and
      environmental protein composition, respectively, for scrutiny by T cells.
      Receptor-mediated endocytosis, phagocytosis, and macropinocytosis all contribute
      to antigen uptake by class II MHC-positive antigen-presenting cells. Capture of
      antigenic peptides by class II MHC molecules is facilitated because antigen
      catabolism and class II MHC maturation take place in the same compartments or in
      communicating compartments of the endosome/lysosome system. These class II MHC
      rich, multivesicular endosomes receive incoming antigen and can support not only
      antigen processing and class II MHC peptide loading but also the export of
      peptide/class II MHC complexes to the cell surface. A balance between production
      and destruction of antigenic peptides is achieved by the activity of local
      proteases and may be influenced by binding of antigen to other proteins both
      prior to the onset of processing (e.g. antibodies) and during antigen unfolding
      (e.g. MHC molecules). T cell determinants that can be released for MHC binding
      without a substantial processing requirement may be able to utilize a distinct
      minor population of cell surface class II MHC molecules that become available
      during peripheral recycling. Although peptides derived from exogenous protein
      sources are usually excluded from presentation on class I MHC molecules, recent
      evidence shows that this embargo may be lifted in certain professional antigen
      presenting cells to increase the spectrum of antigens that may be displayed on
      class I MHC.

PMID- 9143710
TI  - Reinventing public health.
AB  - This chapter is a review of the current state of public health in light of the
      social, political, economic, scientific, and technological changes buffeting the
      United States. As an assessment of progress in current public health efforts, we
      address the five major issues in public health for the 1990s raised by Breslow
      (8): reconstruction of public health; setting objectives for public health; from
      disease control to health promotion; determinants of health and health policy;
      continuing social inequities and their impacts on health; and the health
      implications of accelerating developments in technology. Finally, we look to the
      twenty-first century and provide five clear paths necessary to strengthen the
      capacity of public health agencies to protect and improve the health status of
      the population.

PMID- 9143709
TI  - H2-M3, a full-service class Ib histocompatibility antigen.
AB  - H2-M3 is an MHC class Ib molecule of the mouse with a unique preference for N
      formylated peptides, which may come from the N-termini of endogenous,
      mitochondrial proteins or foreign, bacterial proteins. The crystal structure of
      M3 revealed a hydrophobic peptide-binding groove with an occluded A pocket and
      the peptide shifted one residue relative to class Ia structures. The formyl group
      is held by a novel hydrogen bonding network, involving His9 on the bottom of the
      groove, and the side chain of the P1 methionine is lodged in the B pocket. M3 is
      a full-service histocompatibility (H) antigen, i.e. self-M3 can present
      endogenous peptides as minor H antigens and foreign, bacterial antigens in a
      defensive immune response to infection; and foreign M3 complexed with endogenous
      self-peptides.

PMID- 9143711
TI  - Aspirin in the treatment and prevention of cardiovascular disease.
AB  - Aspirin irreversibly inhibits cyclooxygenase in platelets for their entire
      lifespan, raising the possibility of clinical benefits by decreasing risks of
      occlusive vascular events. In secondary prevention among patients with a wide
      range of prior occlusive vascular events, including myocardial infarction (MI),
      stroke, transient ischemic attacks (TIAs), as well as unstable and chronic stable
      angina, aspirin therapy is associated with a reduction in risks of subsequent MI,
      stroke, and vascular deaths. In acute MI, aspirin also confers clear benefits on
      subsequent MI, stroke, and vascular deaths. In primary prevention, the available
      randomized trial data, which to date are limited to men, indicate a clear
      reduction in risk of a first MI; the current data are inconclusive concerning
      aspirin's effect on stroke and total vascular mortality. A currently ongoing
      trial among 40,000 apparently healthy women will provide reliable data concerning
      the balance of benefits and risks of aspirin in primary prevention.

PMID- 9143712
TI  - Categorical data analysis in public health.
AB  - A greater variety of categorical data methods are used today than 15 years ago.
      This article surveys categorical data methods widely applied in public health
      research. Whereas large sample chi-square methods, logistic regression analysis,
      and weighted least squares modeling of repeated measures once comprised the
      primary analytic tools for categorical data problems, today's methodology is
      comprised of a much broader range of tools made available by increasing
      computational efficiency. These include computational algorithms for exact
      inference of small samples and sparsely distributed data, conditional logistic
      regression for modeling highly stratified data, and generalized estimating
      equations for cluster samples. The latter, in particular, has found wide use in
      modeling the marginal probabilities of correlated counted, binary, and
      multinomial outcomes. The various methods are illustrated with examples including
      a study of the prevalence of cerebral palsy in very low birthweight infants and a
      study of cancer screening in primary care settings.

PMID- 9143713
TI  - Censoring issues in survival analysis.
AB  - A key characteristic that distinguishes survival analysis from other areas in
      statistics is that survival data are usually censored. Censoring occurs when
      incomplete information is available about the survival time of some individuals.
      We define censoring through some practical examples extracted from the literature
      in various fields of public health. With few exceptions, the censoring mechanisms
      in most observational studies are unknown and hence it is necessary to make
      assumptions about censoring when the common statistical methods are used to
      analyze censored data. In addition, we present situations in which censoring
      mechanisms can be ignored. The effects of the censoring assumptions are
      demonstrated through actual studies.

PMID- 9143714
TI  - Survival analysis in public health research.
AB  - This paper reviews the common statistical techniques employed to analyze survival
      data in public health research. Due to the presence of censoring, the data are
      not amenable to the usual method of analysis. The improvement in statistical
      computing and wide accessibility of personal computers led to the rapid
      development and popularity of nonparametric over parametric procedures. The
      former required less stringent conditions. But, if the assumptions for parametric
      methods hold, the resulting estimates have smaller standard errors and are easier
      to interpret. Nonparametric techniques include the Kaplan-Meier method for
      estimating the survival function and the Cox proportional hazards model to
      identify risk factors and to obtain adjusted risk ratios. In cases where the
      assumption of proportional hazards is not tenable, the data can be stratified and
      a model fitted with different baseline functions in each stratum. Parametric
      modeling such as the accelerated failure time model also may be used. Hazard
      functions for the exponential, Weibull, gamma, Gompertz, lognormal, and log
      logistic distributions are described. Examples from published literature are
      given to illustrate the various methods. The paper is intended for public health
      professionals who are interested in survival data analysis.

PMID- 9143715
TI  - Environmental ecology of Cryptosporidium and public health implications.
AB  - Cryptosporidium has become the most important contaminant found in drinking water
      and is associated with a high risk of waterborne disease particularly for the
      immunocompromised. There have been 12 documented waterborne outbreaks in North
      America since 1985; in two of these (Milwaukee and Las Vegas) mortality rates in
      the immunocompromised ranged from 52% to 68%. The immunofluorescence antibody
      assay (IFA) using epifluorescence microscopy has been used to examine the
      occurrence of Cryptosporidium in sewage (1 to 120 oocysts/liter), filtered
      secondary treated wastewater (0.01 to 0.13 oocysts/liter), surface waters (0.001
      to 107 oocysts/liter), groundwater (0.004 to 0.922 oocysts/liter) and treated
      drinking water (0.001 to 0.72 oocysts/liter). New rules are being developed
      (Information Collection Rule and Enhanced Surface Water Treatment Rule) to obtain
      more occurrence data for drinking water systems for use with new risk assessment
      models. Public health officials should consider a communication program to
      physicians treating the immunocompromised, nursing homes, develop a plan to
      evaluate cases of cryptosporidiosis in the community, and contribute to the
      development of public policies that limit contamination of source waters, improve
      water treatment, and protect public health.

PMID- 9143716
TI  - Environmental tobacco smoke: health effects and policies to reduce exposure.
AB  - The health hazards due to exposure to environmental tobacco smoke (ETS) are
      increasingly established. ETS contains thousands of chemicals including 43 known
      carcinogens. Known health effects of ETS exposure are lung cancer in nonsmokers,
      childhood disorders such as bronchitis, and perhaps, heart disease. Workplace
      exposure to ETS is widespread and is influenced strongly by the type of smoking
      policy in the workplace. To decrease ETS exposure, efforts to restrict public
      smoking have proliferated over the past decade. These restrictions have emanated
      from government as well as voluntary measures by various private industries. Bans
      on public smoking are effective in reducing nonsmokers' exposure to ETS.
      Workplace smoking bans also influence the intensity of smoking among employees
      and may increase quit smoking rates. In addition to the health benefits from
      smoke-free workplaces, there are likely cost savings to employers who implement
      such policies.

PMID- 9143717
TI  - Preventing lead poisoning in children.
AB  - Lead poisoning is the most significant and prevalent disease of environmental
      origin among US children. Despite over 100 years' knowledge of the special
      hazards of lead exposure for young children, it has taken over a century for
      effective primary prevention to be adopted. Obstacles to primary prevention have
      included deliberate campaigns by industry to prevent restrictions upon such uses
      on lead as plumbing, paints, and gasoline additives; influence of industrial
      support of biomedical research at major US medical schools: lack of appropriate
      policy mechanisms to identify and control lead exposures; and opposition to
      investing resources in lead poisoning prevention. The removal of lead from
      gasoline, which began in the United States in 1972 and was completed in 1995, has
      resulted in almost fourfold reductions in median blood lead levels in US children
      from 1976 to 1991. Increased screening and interventions to identify and abate
      lead sources, such as lead in housing, also contributed to this major public
      health success. Nevertheless, lead exposures remain prevalent, although
      increasingly less generally distributed. Perhaps because of the renewed
      "ghettoization" of lead, support for lead poisoning prevention has waned.
      Objections to investing public and private resources in screening and source
      abatement have challenged the continuing commitment of public health officials to
      prevention. The demonstrable success and social benefits of preventing lead
      toxicity are cited in support of continued preventive health policies.

PMID- 9143718
TI  - The human health effects of DDT (dichlorodiphenyltrichloroethane) and PCBS
      (polychlorinated biphenyls) and an overview of organochlorines in public health.
AB  - Organochlorines are a diverse group of persistent synthetic compounds, some of
      which are detectable in nearly everyone. Many organochlorines are endocrine
      disruptors or carcinogens in experimental assays. p,p'-DDE (dichlorodiphenyl
      dichloroethene) and PCBs (polychlorinated biphenyls) comprise the bulk of
      organochlorine residues in human tissues. We reviewed relevant human data cited
      in the 1991-1995 Medline database and elsewhere. High-level exposure to selected
      organochlorines appears to cause abnormalities of liver function, skin
      (chloracne), and the nervous system. Of more general interest, however, is
      evidence suggesting insidious effects of background exposure. Of particular
      concern is the finding of neonatal hypotonia or hyporeflexia in relation to PCB
      exposure. The epidemiologic data reviewed, considered in isolation, provide no
      convincing evidence that organochlorines cause a large excess number of cancers.
      A recent risk assessment that considered animal data, however, gives a cancer
      risk estimate for background exposure to dioxin and dioxin-like compounds (e.g.
      some PCBs) with an upper bound in the range of 10(-4) per year.

PMID- 9143719
TI  - Perspectives on the place of environmental health and protection in public health
      and public health agencies.
AB  - The field of environmental health and protection and the entire field of public
      health have repeatedly found themselves isolated from one another, unable to
      articulate the definition, mission, and goals of public health and the essential
      role for environmental health and protection in the provision of a healthy
      ecological and human environment. Environmental agencies often forget that they,
      too, are public health agencies; public health agencies that have had
      environmental health functions have divided and abdicated their environmental
      responsibilities, considering these to be "regulatory" rather than public health.
      This article reviews the history of environmental health and protection, its
      involvement within the field of public health, its eventual separation from other
      public health programs with resulting benefits and consequences, and what the
      future may hold for environmental health and protection activities as well as for
      the broader scope of public health of which these activities are a part.

PMID- 9143720
TI  - From measuring to improving public health practice.
AB  - Efforts to measure public health practice have taken on various forms and focused
      on different aspects of the system of public health practice over the past
      century. Before 1990, measurement was primarily based on a series of self
      assessment instruments initiated under the auspices of the Committee on
      Administrative Practice of the American Public Health Association. These
      instruments emphasized measurement of immediate results of local public health
      services although they also provided information on local resources and capacity
      to perform. Following the Institute of Medicine's report in 1988, efforts began
      to focus on performance related to public health's core functions. These more
      recent assessments suggest that the system of public health practice must be
      improved to achieve the targets of effectiveness established for the year 2000.
      Ultimately, a comprehensive national surveillance system for public health
      practice will need to both measure and examine the relationships among inputs
      (resources, capacity, etc), core function-related processes, outputs (services)
      as well as outcomes.

PMID- 9143721
TI  - The public health aspects of complex emergencies and refugee situations.
AB  - Populations affected by armed conflict have experienced severe public health
      consequences mediated by population displacement, food scarcity, and the collapse
      of basic health services, giving rise to the term complex humanitarian
      emergencies. These public health effects have been most severe in underdeveloped
      countries in Africa, Asia, and Latin America. Refugees and internally displaced
      persons have experienced high mortality rates during the period immediately
      following their migration. In Africa, crude mortality rates have been as high as
      80 times baseline rates. The most common causes of death have been diarrheal
      diseases, measles, acute respiratory infections, and malaria. High prevalences of
      acute malnutrition have contributed to high case fatality rates. In conflict
      affected European countries, such as the former Yugoslavia, Georgia, Azerbaijan,
      and Chechnya, war-related injuries have been the most common cause of death among
      civilian populations; however, increased incidence of communicable diseases,
      neonatal health problems, and nutritional deficiencies (especially among the
      elderly) have been documented. The most effective measures to prevent mortality
      and morbidity in complex emergencies include protection from violence; the
      provision of adequate food rations, clean water and sanitation; diarrheal disease
      control; measles immunization; maternal and child health care, including the case
      management of common endemic communicable diseases; and selective feeding
      programs, when indicated.

PMID- 9143722
TI  - Food safety regulation: reforming the Delaney Clause.
AB  - The safety of food has been an age-old concern. Early civilizations adopted laws
      that punished sellers of tainted food. In this country, before food safety became
      a responsibility of the federal government every state had enacted laws
      prohibiting the sale of food that contained poisonous substances. The modern
      scientific and legal instruments available to the US Food and Drug Administration
      and allied agencies have improved regulation and advances in food preparation,
      preservation, and storage have contributed to a safer food supply. Even so, some
      observers believe that contemporary threats to food safety have grown more
      serious, and they surely excite intense public concern. For nearly two decades
      Congress has been debating the adequacy of current laws governing food safety. In
      the closing months of the 104th Congress, both parties finally agreed on the
      first significant legislative change in over a generation. This chapter examines
      the origins of the issues that were the focus of this extended debate and
      analyzes the implications of their resolution.

PMID- 9143723
TI  - Measuring social class in US public health research: concepts, methodologies, and
      guidelines.
AB  - Increasing social inequalities in health in the United States and elsewhere,
      coupled with growing inequalities in income and wealth, have refocused attention
      on social class as a key determinant of population health. Routine analysis using
      conceptually coherent and consistent measures of socioeconomic position in US
      public health research and surveillance, however, remains rare. This review
      discusses concepts and methodologies concerning, and guidelines for measuring,
      social class and other aspects of socioeconomic position (e.g. income, poverty,
      deprivation, wealth, education). These data should be collected at the
      individual, household, and neighborhood level, to characterize both childhood and
      adult socioeconomic position; fluctuations in economic resources during these
      time periods also merit consideration. Guidelines for linking census-based
      socioeconomic measures and health data are presented, as are recommendations for
      analyses involving social class, race/ethnicity, and gender. Suggestions for
      research on socioeconomic measures are provided, to aid monitoring steps toward
      social equity in health.

PMID- 9143724
TI  - Moral and policy issues in long-acting contraception.
AB  - The advent of reversible long-acting contraceptives-IUDs, injectables and
      implants-has provided women throughout the world with valuable new fertility
      regulation options. These highly effective methods, together with male and female
      sterilization, have proven to be enormously popular and are now used by the
      majority of women and men who are currently contracepting worldwide. Despite
      their remarkable popularity, long-acting contraceptives have engendered
      considerable controversy. Political, ethical, and safety questions have emerged,
      stemming from the ways in which these contraceptives have been developed and used
      over the course of this century. At the heart of the concern is the issue of
      reproductive rights and freedom. This paper reviews the history of the
      development of long-acting contraceptives, including the prospect of new methods
      that will likely emerge from ongoing research and development. It also examines
      the history, in the United States and in developing countries, of the use and
      abuse of long-acting methods, including sterilization, in the context of eugenics
      and population control policies. It then describes a new paradigm of reproductive
      health and rights that has emerged from the International Conference on
      Population Development in Cairo, and which offers an enlightened approach to
      future policies and programs. In light of the wide variety of ways in which long
      acting contraceptives have been provided, the paper examines the rights and
      responsibilities of governments, family planning providers, and individuals. An
      ethical framework for the use of long-acting methods is discussed, and public
      policies for the future are proposed.

PMID- 9143725
TI  - Reframing women's risk: social inequalities and HIV infection.
AB  - Social inequalities lie at the heart of risk of HIV infection among women in the
      United States. As of December, 1995, 71,818 US women had developed AIDS-defining
      diagnoses. These women have been disproportionately poor, African-American, and
      Latina. Their neighborhoods have been burdened by poverty, racism, crack cocaine,
      heroin, and violence. To explain which women are at risk and why, this article
      reviews the epidemiology of HIV and AIDS among women in light of four conceptual
      frameworks linking health and social justice: feminism, social production of
      disease/political economy of health, ecosocial, and human rights. The article
      applies these alternative theories to describe sociopolitical contexts for AIDS'
      emergence and spread in the United States, and reviews evidence linking
      inequalities of class, race/ethnicity, gender, and sexuality, as well as
      strategies of resistance to these inequalities, to the distribution of HIV among
      women.

PMID- 9143726
TI  - Searching for the biological pathways between stress and health.
AB  - Population-based, person-specific health surveys, with concomitant biological
      measures, should provide important information about the processes by which
      socioeconomic and psychosocial factors embed themselves in human health.
      Questionnaire responses allow for assessment of the perceived psychosocial
      environment, but biological measurements will measure the status of the
      psychoneuroimmunology/ psychoneuroendocrinology (PNI/PNE) pathways and may allow
      us to identify people who have "adapted" to their stress because of experience,
      expectations, stoicism, etc. This review sets criteria to evaluate potential
      physiological markers of chronic stress. Because population health surveys
      involve a massive number of samples, special consideration must be given to the
      laboratory analysis method and transportation time of the markers chosen. We
      reviewed five areas: glycosylated proteins, the immune system, hemostasis
      peripheral benzodiazepine receptors, and the waist-hip ratio.

PMID- 9143727
TI  - The effects of poverty on child health and development.
AB  - Poverty has been shown to negatively influence child health and development along
      a number of dimensions. For example, poverty-net of a variety of potentially
      confounding factors-is associated with increased neonatal and postneonatal
      mortality rates, greater risk of injuries resulting from accidents or physical
      abuse/neglect, higher risk for asthma, and lower developmental scores in a range
      of tests at multiple ages. Despite the extensive literature available that
      addresses the relationship between poverty and child health and development, as
      yet there is no consensus on how poverty should be operationalized to reflect its
      dynamic nature. Perhaps more important is the lack of agreement on the set of
      controls that should be included in the modeling of this relationship in order to
      determine the "true" or net effect of poverty, independent of its cofactors. In
      this paper, we suggest a general model that should be adhered to when
      investigating the effects of poverty on children. We propose a standard set of
      controls and various measures of poverty that should be incorporated in any
      study, when possible.

PMID- 9143728
TI  - A national strategy for research and development: lessons from England.
AB  - Increasing concern about the state of basic and clinical research in England
      during the 1980s led to an influential parliamentary review. Surprisingly, the
      review recommended the strengthening of public health and health services
      research through the establishment of a research and development (R&D) program
      for the National Health Service (NHS). The program that started in 1991 was
      unique in that it was fully integrated into the management structure of the NHS.
      No country had ever attempted such an ambitious approach. While a review of the
      first five years of the program reveals many achievements, it also raises several
      concerns: Debate about the philosophy and aims of the program continues; the need
      to maintain political support requires constant attention; policy changes in
      other areas need to be accommodated; central control of a national, coordinated
      R&D program has to be guarded; methods of priority setting need to be enhanced;
      insufficient human resources to run the program have to be contended with; and
      the program needs to be rigorously evaluated. Other countries with a unified
      health system could learn much from the English experience. Countries with
      pluralist systems might benefit from specific parts of the experience.

PMID- 9143729
TI  - Consumer health plan choice: current knowledge and future directions.
AB  - A keystone of the competitive strategy in health insurance markets is the
      assumption that "consumers" can make informed choices based on the costs and
      quality of competing health plans, and that selection effects are not large.
      However, little is known about how individuals use information other than price
      in the decision making process. This review summarizes the state of knowledge
      about how individuals make choices among health plans and outlines an agenda for
      future research. We find that the existing literature on health plan choice is no
      longer sufficient given the widespread growth and acceptance of managed care, and
      the increased proportion of consumers' income now going toward the purchase of
      health plans. Instead, today's environment of health plan choice requires better
      understanding of how plan attributes other than price influence plan choice, how
      other variables such as health status interact with plan attributes in the
      decision making process, and how specific populations differ from one another in
      terms of the sensitivity of their health plan choices to these different types of
      variables.

PMID- 9143730
TI  - Pharmacoeconomics: state of the art in 1997.
AB  - Economic evaluation of pharmaceutical products, or pharmacoeconomics, is a
      rapidly growing area of research. Pharmacoeconomic evaluation is important in
      helping clinicians and managers make choices about new pharmaceutical products
      and in helping patients obtain access to new medications. Over the last few
      years, the scientific rigor of this field has increased greatly. At the same
      time, new types of analysis, based on prospective data collection, have been
      developed. This article reviews the basic concept of pharmacoeconomics, the types
      of data available for economic evaluation, and the "state of the art" in
      pharmacoeconomics as reported in the medical literature.

PMID- 9143731
TI  - Physician payment policies: impacts and implications.
AB  - This paper reviews recent changes in physician payment policies, examines
      evidence on their impacts, and discusses their implications for researchers and
      policy makers. It first develops a conceptual framework to help explore the
      economic incentives inherent in different physician payment schemes. It then
      reviews evidence on the impacts of recent changes in physician payment methods;
      first, for free-for-service, and then for capitated systems like HMOs. It
      concludes that much more research needs to be conducted on HMOs to determine the
      impact of different physician payment incentives on utilization, expenditures,
      clinical outcomes, and patient satisfaction.

PMID- 9143732
TI  - School-based health clinics: remaining viable in a changing health care delivery
      system.
AB  - Adolescents are often vulnerable to particular health risks and face multiple
      barriers to accessing health care. School-based clinics and school-linked
      services represent an alternative model of care that has responded to the unique
      health issues of adolescents by offering preventive, comprehensive services,
      including mental health and other sensitive services. The current restructuring
      of the American health care delivery system presents a serious challenge to the
      continued existence of these services, which must link successfully with managed
      care organizations and adapt to significant changes in federal and state funding
      streams to remain viable. The continued success of school-based health services
      in improving adolescent health will largely depend on how well they can
      capitalize on their strategic position to reach adolescents, respond to their
      health needs, and reduce barriers to care, and how effectively they can integrate
      themselves into a rapidly evolving US health care delivery system.

PMID- 9143733
TI  - Analysis of microsatellite instability and loss of heterozygosity in
      keratoacanthoma.
AB  - We analyzed microsatellite instability (MSI) and loss of heterozygosity (LOH) at
      17 microsatellite markers located on chromosomes 2p, 3p, 5q, 6q, 9p, 9q, 17p and
      18q in 19 randomly selected keratoacantomas (KAS), in one cutaneous lesion that
      histologically could not unequivocally be differentiated from squamous cell
      carcinoma, and in one patient with multiple KAs of longstanding duration. The
      goals of our study were to determine whether, in a similar manner to some
      visceral carcinomas, genomic instability could be detected in KAs and to clarify
      whether molecular analysis might be useful to further characterize KA. MSI was
      observed in 2 of 21 cases (9.5%) at 5 of 17 loci examined. In one patient with a
      solitary KA, the presence of MSI and a family history of visceral malignant
      tumours suggested that the patient might have belonged to a family with Muir
      Torre syndrome. In one other MSI+ KA, a definite differential diagnosis in
      relation to squamous cell carcinoma could not be established. In addition, one
      sample displayed LOH at 2 of 17 loci analysed whereas in the patient with
      multiple KAs, LOH at one locus was the only alteration found. In conclusion, the
      low frequency of MSI and LOH detected in our study suggests that these genetic
      events are uncommon in KA unless it is associated with a familial disease (e.g.
      Muir-Torre syndrome) or it has more aggressive histological features.

PMID- 9143734
TI  - Pentoxifylline inhibits human T-cell adhesion to dermal endothelial cells.
AB  - Pentoxifylline (PTX), a methyl xanthine derivative with phosphodiesterase
      inhibitory activity, has been shown to have antiinflammatory effects. Previous
      studies have demonstrated that PTX can suppress TNF alpha production and
      function, and can inhibit the adhesion of neutrophils and monocytes to
      endothelial cells. In the present study, we sought to determine whether PTX also
      interferes with the adhesion of human peripheral blood T lymphocytes to cells of
      the human dermal endothelial cell line HMEC-1. Using a cell adhesion immunoassay,
      the effect of different doses of PTX (10(-5)-10(-2) M) on the binding of
      unactivated or PMA-activated T cells to unstimulated or TNF alpha-stimulated
      endothelial cells was investigated. In addition, blocking experiments with
      monoclonal antibodies against pairs of adhesion molecules known to be involved in
      endothelial cell/T-cell adhesion were performed. Unactivated T cells showed
      minimal adhesion to unstimulated endothelial cells. PMA-activated T cells showed
      an eightfold increased binding to TNF alpha-stimulated endothelial cells, which
      was found to be mediated largely by LFA-1/ICAM-1. PTX inhibited the binding of
      PMA-activated T cells to TNF alpha-stimulated endothelial cells in a dose
      dependent manner. This inhibition was only found when PTX was present during the
      adhesion assay. A similar inhibition was found when PTX was replaced by
      isobutylmethylxanthine, another methyl xanthine derivative, or by a combination
      of two cAMP analogues. The results suggest that interference with T
      cell/endothelial cell adhesion, which forms an essential step in the migration of
      T cells from the peripheral blood into sites of inflammation, may be another
      explanation for the beneficial effect of PTX in several inflammatory dermatoses.

PMID- 9143735
TI  - Heterotypic cell-cell adhesion of human mast cells to fibroblasts.
AB  - Skin mast cells are typically located in the perivascular or perineural
      connective tissue. We observed that HMC-1 mast cells growing in suspension
      adhered efficiently to (> 90% of cells) and spread on top of fibroblast
      monolayers and to a lesser degree on purified extracellular matrix proteins.
      Since adhesive interactions determine cell migration and tissue localization we
      studied the mechanism. It was found that HMC-1 cells attach to collagen I and
      fibronectin, laminin, collagen IV and vitronectin, but not to collagens III and
      VI or hyaluronic acid. Adhesion to fibronectin, collagen I and laminin was
      completely inhibited by mAbs blocking beta 1-integrins, whereas adhesion of HMC-1
      cells to vitronectin was inhibited by anti-alpha v-chain mAbs. However,
      attachment of HMC-1 cells to fibroblasts was not influenced by mAbs blocking beta
      1- or alpha v-chain function, by RGD peptides or by mAbs interfering with other
      receptors, most notably c-kit. Identical results were obtained with normal mast
      cells isolated from human foreskin. These results indicate that human mast cells
      attach to fibroblasts independently of beta 1- or alpha v-integrins as well as of
      c-kit receptor-mediated mechanisms. The functional characteristics observed (i.e.
      only partial sensitivity to trypsin and EDTA, no increase in trypsin sensitivity
      by pretreatment with EDTA) suggest that cadherin receptors were not involved, and
      it is likely that the adhesion process observed involved not-yet-defined
      heterotypic cell-cell adhesion receptors.

PMID- 9143736
TI  - Role of melanoma growth stimulatory activity (MGSA/gro) on keratinocyte function
      in wound healing.
AB  - Melanoma growth stimulatory activity/gro alpha (MGSA), a member of the alpha
      chemokine family, is produced by a variety of dermal and epidermal cells and can
      act in a paracrine and autocrine fashion. However, little is known about the
      importance of MGSA in wound healing. In this study, we quantified the levels of
      MGSA protein in burn blister and donor site wound fluids. We studied the effects
      of MGSA on proliferation and migration of primary human keratinocytes and
      modulation of their integrin expression. Blister fluids contained 0.79 ng/ml
      (range 0.018 to 4.86 ng/ml) MGSA. Substantial increasing amounts of MGSA were
      found in donor site fluids from day 1 through day 5 with mean levels ranging from
      1.77 to 103 ng/ml at postoperative day 5, which correlated with increasing
      amounts of tumor necrosis factor alpha (r = 0.86), a known stimulus for MGSA
      production. In vitro proliferation experiments revealed a maximum stimulation
      (2.6-fold) with 10 ng/ ml MGSA for 7 days over unstimulated keratinocyte
      controls; the ED50 was 0.2 ng/ml. DNA content analysis revealed an increase in S
      phase with 10 ng/ml MGSA stimulation. In cultured keratinocytes, MGSA enhanced
      the mean fluorescence intensity for alpha 6, while no significant change was seen
      for beta 1, alpha 2 and alpha 5. We also studied the effect of topically applied
      MGSA (50 ng/cm2) on the healing of meshed split-thickness human skin grafts on
      athymic mice. In these wounds, MGSA stimulated the rate of epithelialization (P <
      0.05) at day 7, and an increased proportion of mitotic keratinocytes was
      observed. Wound contraction was significantly (P < 0.05) reduced on days 7 and 14
      in the MGSA-treated group. These results suggest that MGSA participates in wound
      healing by stimulating keratinocyte proliferation.

PMID- 9143737
TI  - New immunodeficient (nude-scid, beige-scid) mice as excellent recipients of human
      skin grafts containing intraepidermal neoplasms.
AB  - Engraftment of normal or lesional human skin onto nude or SCID (severe combined
      immunodeficiency) mice has been used as an in vivo experimental model. However,
      this model has some limitations, such as shrinkage and loss of the grafted skin
      over time. To improve the experimental model, we have produced two new SCID
      lineage mouse strains, BALB/cA-nude-scid (nu/nu, scid/scid) and BALB/cA-beige
      scid (bg/bg, scid/scid) mice, by the method of cross intercross. Intraepidermal
      neoplastic lesions such as Bowen's disease were grafted onto the back of the mice
      of these strains. The rate of reduction in the size of the grafts was lower on
      nude-scid and beige-scid mice than on SCID mice. Rates of survival of neoplastic
      cells in the grafts were higher in nude-scid mice than in SCID and beige-scid
      mice (SCID mice 38%, nude-scid mice 55%, beige-scid mice 38%). Neoplastic cells
      of Bowen's disease grafted onto a beige-scid mouse proliferated and invaded the
      dermis during 233 days of observation, confirming the progression to invasive
      squamous cell carcinoma from carcinoma in situ. The present study revealed that
      nude-scid and beige-scide mice newly produced by us provide a very useful in vivo
      experimental model for the investigation of carcinogenesis and tumor progression
      in human skin.

PMID- 9143738
TI  - The effects of interleukin-1 and prostaglandin E2 on accumulation of collagen and
      steady-state levels of pro alpha 1(I) collagen messenger RNA in experimental
      granulation tissue in rats.
AB  - The effects of human interleukin 1 beta (IL-1 beta) and prostaglandin E2 (PGE2)
      on experimental granulation tissue in rats and on granulation tissue cells in
      culture were studied. IL-1 beta and PGE2 were injected into subcutaneously
      implanted sponges during the first 3 days after implantation. The rate of
      collagen synthesis in fibroblasts was measured as synthesis of protein-bound 3H
      hydroxyproline. The steady-state levels of pro alpha 1(I) and pro alpha 1(III)
      collagen chain mRNAs were estimated by Northern transfer analyses. By 7 days
      postoperatively IL-1 beta had decreased the hydroxyproline content of granulation
      tissue. PGE2 decreased non-significantly the amounts of hydroxyproline, but the
      steady-state levels of pro alpha 1(I) and pro alpha 1(III) collagen chain mRNAs
      were slightly elevated. In IL-1 beta-treated fibroblast cultures collagen
      production decreased by 15% and following PGE2 treatment by 34% compared with the
      controls. The latter effect could be abolished by indomethacin. Indomethacin
      alone stimulated collagen production by 40%. In vivo IL-1 decreases the formation
      of normal granulation tissue. This effect may be partly due to stimulation of
      secretion of PGE2.

PMID- 9143739
TI  - Establishment and characterization of an epithelioid sarcoma cell line with an
      autocrine response to interleukin-6.
AB  - A novel epithelioid sarcoma (ES) cell line, designated as ES-OMC-MN, was
      established from a 44-year-old woman with recurrence and metastasis of ES. The
      cells were spindle-shaped or polygonal and were positive for cytokeratin and
      vimentin on immunohistochemical staining. Electron microscopy revealed desmosome
      like structures between the cells. These characteristics were also noted in the
      original tumor. Southern blot analysis of HindIII digests showed an additional
      8.0 kb band and an 8.8 kb band in DNA from the cultured cells and the original
      tumor as well as the peripheral blood cells of the patient, while only an 8.8 kb
      band was observed in control human placental DNA. There were no point mutations
      of N-ras codons 12, 13, and 61, suggesting that the abnormality of N-ras was not
      due to mutation but to polymorphism. Interleukin-6 (IL-6) was secreted into the
      culture medium at high levels. Recombinant IL-6 augmented the proliferation of
      these cells, while cell growth was inhibited by incubation with an anti-IL-6
      antibody. The cells also expressed surface IL-6 receptors, indicating that IL-6
      acted on this cell line in an autocrine manner. IL-6 and IL-6 receptors were also
      found in the original tumor. These results demonstrate that ES-OMC-MN cells
      retained all the morphological and biochemical characteristics of the original
      tumor and suggest that an autocrine effect of IL-6 may be involved in the
      development of ES.

PMID- 9143741
TI  - Atopic dermatitis, non-immunologic factors in this frequent skin disease.

PMID- 9143740
TI  - Suppressive effect of monosaccharides on ICAM-1/CD54 expression in human
      keratinocytes.

PMID- 9143742
TI  - Expression of vimentin in human keratinocytes.

PMID- 9143743
TI  - First, do no harm: the role of defibrillators and advanced medical care in
      commercial aviation.
AB  - Primum non nocere-First, do no harm. How often have we as physicians and health
      care providers heard those words? We at American Airlines did not wish to put
      even one person in harm's way by not having care available to save a life in a
      remote commercial aviation environment. The decision was purely a business
      decision of the AMR corporation, who always keeps the welfare of the customer at
      the fore. It may not be the right choice for the entire commercial aviation
      industry under an FAA mandate. We know that we will save lives of persons
      traveling on American Airlines with this program. If the 'ripple' that we have
      started expands to affect the practices of other commercial air carriers in the
      domestic United States, American's reward will be a great one-to know that the
      lives of many people will be saved because one air carrier has taken the first
      step.

PMID- 9143744
TI  - The psychophysiological assessment method for pilot's professional reliability.
AB  - BACKGROUND: Previous research has shown that a pilot's professional reliability
      depends on two relative factors: the pilot's functional state and the demands of
      task workload. The Psychophysiological Reserve Capacity (PRC) is defined as a
      pilot's ability to accomplish additive tasks without reducing the performance of
      the primary task (flight task). HYPOTHESIS: We hypothesized that the PRC was a
      mirror of the pilot's functional state. The purpose of this study was to probe
      the psychophysiological method for evaluating a pilot's professional reliability
      on a simulator. METHODS: The PRC Comprehensive Evaluating System (PRCCES) which
      was used in the experiment included four subsystems: a) quantitative evaluation
      system for pilot's performance on simulator; b) secondary task display and
      quantitative estimating system; c) multiphysiological data monitoring and
      statistical system; and d) comprehensive evaluation system for pilot PRC. Two
      studies were performed. In study one, 63 healthy and 13 hospitalized pilots
      participated. Each pilot performed a double 180 degrees circuit flight program
      with and without secondary task (three digit operation). The operator
      performance, score of secondary task and cost of physiological effort were
      measured and compared by PRCCES in the two conditions. Then, each pilot's flight
      skill in training was subjectively scored by instructor pilot ratings. In study
      two, 7 healthy pilots volunteered to take part in the experiment on the effects
      of sleep deprivation on pilot's PRC. Each participant had PRC tested pre- and
      post-8 h sleep deprivation. RESULTS: The results show that the PRC values of a
      healthy pilot was positively correlated with abilities of flexibility, operating
      and correcting deviation, attention distribution, and accuracy of instrument
      flight in the air (r = 0.27-0.40, p < 0.05), and negatively correlated with
      emotional anxiety in flight (r = -0.40, p < 0.05). The values of PRC in healthy
      pilots (0.61 +/- 0.17) were significantly higher than that of hospitalized pilots
      (0.43 +/- 0.15) (p < 0.05). The PRC value after 8 h sleep loss (0.50 +/- 0.17)
      was significantly lower than those before sleep loss (0.70 +/- 0.15) (p < 0.05).
      CONCLUSION: We conclude that a pilot's PRC, which was closely related to flight
      ability and functional state, could partly represent the pilot's professional
      reliability. It is worthwhile to further research using a pilot's PRC as a
      predictor of mental workload in aircraft design.

PMID- 9143745
TI  - Number of chronic conditions and professional longevity of aviators.
AB  - METHODS: The number of chronic medical conditions (NCMC) experienced by an
      individual may be a measure of health and predictor of the disqualification of
      aviators. Subjects were 727 medically disqualified and 807 current pilots and
      navigators in the Russian Air Forces. All chronic conditions reported in medical
      files were extracted. RESULTS: Disqualification was earlier for subjects who had
      diagnoses of chronic conditions at age 29 (chi 2 = 82.24, p < 0.0001).
      Disqualification was proportionate to the NCMC at age 32 (chi 2 = 98.32, p <
      0.0001) and at 37 (chi 2 = 105.41, p < 0.0001). For 37-yr-old aviators age at
      disqualification was influenced more by the NCMC than by military rank.
      DISCUSSION: The NCMC influenced subsequent disqualification for many years after
      health assessment. This influence was significant and independent from the
      aviator's speciality, final military rank, position, age at entering flying
      school, or town or country of origin. CONCLUSION: NCMC is a good measure of
      health and predictor of disqualification of aviators.

PMID- 9143746
TI  - Human subject research at Armstrong Laboratory, 1973-93: medical and
      musculoskeletal disqualifications.
AB  - The reasons for disqualification of human subjects from 1973-93 at Armstrong
      Laboratory, formerly the Harry G. Armstrong Aeromedical Research Laboratory
      (AAMRL), are presented for both sustained and impact acceleration panels.
      Evaluations for both medical and spinal anomalies were accomplished. The
      rationale for each disqualification is discussed, demonstrating the variability
      in each panel physician's clinical judgment in the context of personal bias, the
      ethical framework surrounding the use of human volunteers, and the existing
      research milieu.

PMID- 9143747
TI  - Carbohydrate-electrolyte solution effects on physical performance of military
      tasks.
AB  - BACKGROUND: Physical performance of military tasks can deteriorate during field
      training. HYPOTHESIS: Drinking a carbohydrate-electrolyte (CHO-E) beverage during
      military relevant training would improve fluid and caloric intake, and better
      sustain physical performance. METHODS: Some 27 volunteers restricted to
      approximately 2600 kcal.d-1 were randomly assigned to one of three groups: CHO-E,
      placebo, or water. Fluid intake was ad libitum. The volunteers completed 3 d of
      field training in hot humid conditions (30 degrees C, 60% rh). Training days 1
      and 2 each included a 16-21 km march over hilly terrain, marksmanship training,
      and 2 h of rock climbing. Day 3 included a 14.5 km march followed by marksmanship
      tests, a timed rock climb and a 0.7 km uphill (21% grade) run. RESULTS: The CHO-E
      beverage provided an additional approximately 2800 kcal (p < 0.05) for the 3 d of
      training. There were no differences (ANOVA, p > 0.05) between the groups absolute
      or changes from pre-training values for fluid intake, body weight, climb time,
      run time, marksmanship, or mood. Those drinking CHO-E were, however, more likely
      to maintain uphill run performance after training (chi 2 = 7.2; p < 0.05) and
      more likely to maintain both uphill run and marksmanship ability (chi 2 = 17.2; p
      < 0.05). There was also an inverse relationship between caloric intake and
      deterioration of uphill run performance (r = -0.75; p < 0.05). CONCLUSIONS:
      Persons drinking CHO-E or practicing good food discipline are more likely to
      sustain physical performance than those eating only a portion of their food. CHO
      E provides an accessible source of calories which can be advantageous when
      limited food is available or inadaquate food consumption is likely.

PMID- 9143749
TI  - Frequency effect of 0.35-1.0 Hz horizontal translational oscillation on motion
      sickness and the somatogravic illusion.
AB  - BACKGROUND: Low frequency translational oscillation can provoke motion sickness
      in land vehicles, ships and aircraft. HYPOTHESIS: Nauseogenicity should decrease
      towards the higher frequencies. METHODS: Some 12 subjects were exposed to
      horizontal sinusoidal motion (3.6 m.s-2 peak) at four different frequencies 0.35,
      0.50, 0.70, and 1.00 Hz, at 1-week intervals, latin square order. Subjects were
      seated in the upright position; motion was through the head-body X-axis. Motion
      was stopped (motion endpoint) at moderate nausea or after 30 min. RESULTS: The
      proportion of subjects experiencing moderate nausea decreased towards the higher
      frequency: 9/12 at 0.35 Hz, 3/12 at 0.50 Hz, 0/12 at 0.70 Hz, and 2/12 at 1.00
      Hz. The mean time to motion endpoint increased significantly (p < 0.001) towards
      the higher frequency: 17.4 min 0.35 Hz; 26.0 min 0.50 Hz; 30 min 0.70 Hz; 28.3
      min 1.00 Hz. Differences between frequencies were significant (0.001 < p < 0.05)
      except for 0.70 Hz to 1.00 Hz. At all frequencies tested, horizontal stimuli were
      more nauseogenic than predicted by mathematical models based on the frequency and
      intensity of vertical oscillation. Somatogravic illusion (SGI) was reported by
      9/12 subjects (mean illusory tilt angles 15.6 degrees forward, 14.1 degrees
      back). SGI tended to diminish at the higher frequencies, but there was no
      relationship between SGI and motion sickness. CONCLUSIONS: These results confirm
      previous findings (9), and furthermore indicate that horizontal X-axis
      translational oscillation has greatly reduced nauseogenic potential at
      frequencies greater than 0.5 Hz. A mathematical model is proposed to predict
      motion sickness intensity and incidence due to this stimulus, which may also be
      applicable to equivalent Y-axis motion.

PMID- 9143748
TI  - Effects of exercise during head-down bed rest on postural control.
AB  - BACKGROUND: The effects of exercise on postural control during walking were
      evaluated following exposure to head-down bed rest (BR). METHODS: Two groups of
      male subjects (N = 18, mean age = 21.4 yr +/- SE 1.0) were exposed to 5 d of 6
      degrees head-down bed rest. The experimental group (E) exercised 90 min.d-1 (n =
      12 subjects) during the BR while the control group received no intervention (n =
      6). The exercise treatment consisted of a combination of isotonic and isokinetic
      lower extremity exercise training. Electromyographic (EMG) activity in the
      tibialis anterior, gastrocnemius, vastus lateralis, and biceps femoris was
      measured during walking before and after BR. RESULTS: Following BR, EMG activity
      increased in both test subject groups for all muscles (p < 0.05). However, there
      were no significant differences in EMG activity between the C and E groups either
      before or after BR. CONCLUSIONS: These data suggest that the ability of the
      postural control system to adjust to the gravitational environment was
      compromised as a result of BR. In addition, we conclude that the exercise
      protocol used was not an effective countermeasure to the alterations in the
      postural control system.

PMID- 9143750
TI  - Influence of a reduced G-suit pressure schedule on G-duration tolerance using
      enhanced G-protection ensembles.
AB  - BACKGROUND: Reducing pressure to enhanced G-protection ensembles may diminish
      potential undesirable physiologic effects, as well as improve wear comfort and
      garment durability. HYPOTHESIS: G-duration tolerance will not be affected by
      reducing pressure to the Swedish tactical flight combat suit (TFCS). A second
      objective tested the similarity in G-duration tolerance between the TFCS and
      Combined Advanced Technology Enhanced Design G-Ensemble (COMBAT EDGE) combined
      with a prototype enhanced coverage G-suit. METHODS: There were 12 Swedish pilots
      (mean = 30 yr) who experienced gradual onset (+0.1 G.s-1) runs (GOR) to +9 Gz,
      rapid (+6 G.s-1) onset runs (ROR) and simulated aerial combat maneuvers (SACM)
      with +5 to +9 Gz cycles. The GOR and ROR profiles had a sustained times of 60 s
      after reaching +9 Gz. RESULTS: GOR duration tolerance was statistically decreased
      (p < 0.01) by the lower pressure (1.1 psig.G-1) when compared to standard
      pressure (1.5 psig.G-1). No statistical difference between TFCS and COMBAT EDGE
      was observed during the GOR trials. For all conditions, during the RORs, 90% of
      the subjects completed at least 30 s at +9 Gz. Many technical or medical
      difficulties during SACM trials limited statistical treatment of these data.
      However, no obvious among-condition differences were observed. Noteworthy among
      SACM trials were those of 3 subjects enduring more than 9 min before stopping;
      one completing 12.5 min (35 cycles). Neither heart rate, blood pressure, nor
      perceived exertion data revealed a condition-effect difference. CONCLUSION:
      Moderately reduced pressure to the extended coverage anti-G suit, combined with
      positive pressure breathing, may yield decreased G-tolerance results during
      laboratory evaluation; however, observed differences are sufficiently small they
      are likely operationally insignificant.

PMID- 9143751
TI  - Hypoxic syncope.
AB  - INTRODUCTION: Syncope at altitude of otherwise healthy individuals is a well
      known phenomenon (22). We report on the cardiovascular effects observed in
      subjects exposed to hypoxia to illustrate the role of the sympathetic-adrenergic
      system in hypoxic syncope. This study describes unexpected episodes of (near)
      syncope during two crossover trials at simulated altitude in a low pressure
      chamber. METHODS: In study A, 30 healthy male volunteers underwent 4 exposures to
      short-term (20 min) acute severe hypoxia (20,000 ft or 6096 m) to assess
      psychological performance. In study B, five volunteers were studied during
      prolonged exposure (1 h) to moderate hypoxia (13,500 ft or 4115 m) with and
      without concomitant low dose infusion with atrial natriuretic peptide to
      investigate the effects on pulmonary gas exchange. RESULTS: In study A (acute
      severe hypoxia), 6 out of 120 exposures (5%), in 5 subjects, were accompanied by
      lightheadedness, pallor, sweating, and bradycardia. Two subjects (2%) had syncope
      with cardiac asystole. In study B during moderate hypoxia without atrial
      natriuretic peptide, adverse reactions were absent and the (nor)epinephrine
      levels remained unchanged. Concomitant infusion with atrial natriuretic peptide
      resulted in near syncope (recumbent in 3, standing in 2) at an oxygen saturation
      of 82%. While the epinephrine level had eightfold increased, mean arterial
      pressure fell from 94 to 40 mm Hg and heart rate from 79 to 44 bpm. The
      norepinephrine level remained unchanged illustrating a dissociated sympathetic
      adrenergic response. All subjects with syncope recovered spontaneously within few
      minutes in Trendelenburg's position with oxygen supplied. None suffered from
      prolonged side effects. CONCLUSION: It is concluded that exposure to acute severe
      hypoxia is a sufficient cause for syncope in healthy individuals. Enhanced
      vasodilatation to epinephrine may contribute to the withdrawal of sympathetic and
      enhancement of parasympatic activity, leading to vascular collapse, bradycardia
      or asystole (Bezold-Jarisch reflex). Patients fully recover in Trendelenburg's
      position with supplemental oxygen and further clinical examinations are not
      necessary.

PMID- 9143752
TI  - Hyperthermia-induced cardiac arrest in monkeys: limited efficacy of standard CPR.
AB  - BACKGROUND: Successful resuscitation from heatstroke cardiopulmonary arrest has
      been only partially explored and the data covering the post resuscitation
      pathophysiology leading to secondary arrest is, in most cases, insufficient.
      HYPOTHESIS: Following heatstroke-cardiopulmonary arrest, successful resuscitation
      may be achieved by standard CPR with surface cooling and administration of
      glucose. We ponder the sequence of early circulatory responses and the
      pathophysiological changes following successful resuscitation. METHODS: We
      exposed 12 pigtail monkeys to total-body hyperthermia (cerebral T 42 degrees C)
      until cardiac arrest ensued. Standard external CPR with surface cooling and
      glucose 5% IV were administered for up to 30 min. Control group A (n = 6) was
      compared with experimental group B (n = 6), which received additional steroid,
      glucagon and hypertonic glucose during CPR attempts. RESULTS: No significant
      differences were found between the outcome of the two groups. The 30-min CPR
      attempt succeeded in restoration of spontaneous circulation (ROSC) in 8/12
      monkeys-5 animals from group A and 3 in group B. The animals in whom
      resuscitation was unsuccessful had significantly prolonged periods of rectal
      temperature exceeding 42.5 degrees C (p < 0.05), and significantly higher rectal
      temperatures at the end of 30 min of CPR and cooling (p < 0.05). All the
      resuscitated animals later rearrested at 158 +/- 68 (95-228) min after ROSC;
      pulmonary edema occurred in 6/8 animals. CONCLUSIONS: We conclude that
      experimentally-induced heatstroke can be transiently reversed by standard
      resuscitative procedures, but is followed by a delayed, irreversible, secondary
      shock state, which could not be prevented by the treatment we employed. We were,
      however, able to document in detail the pathophysiologic processes involved in
      the resuscitation, and the irreversible shock one sees after "successful" CPR.

PMID- 9143753
TI  - Influence of two weeks of non-weight bearing on rat soleus motoneurons and muscle
      fibers.
AB  - BACKGROUND: Chronic unloading of the hindlimbs of rats results in atrophy and a
      shift in the metabolic and mechanical properties of the soleus muscle a
      predominantly slow postural muscle, towards those observed in faster muscles.
      HYPOTHESIS: We hypothesized that the spinal motoneurons innervating the soleus
      muscle would also atrophy and show adaptations in their metabolic properties
      following a period of unloading. METHODS: For 2 weeks, 10-week-old male Wistar
      rats were hindlimb suspended and the mean soma size and succinate dehydrogenase
      activity of motoneurons innervating the soleus muscle were examined. Retrograde
      labeling with nuclear yellow injected in the soleus muscle was used to identify
      the soleus motor pool. The mean fiber size and fiber type distribution from a
      central region of each soleus muscle was determined. RESULTS: The soma size
      distribution, mean soma cross-sectional area and mean succinate dehydrogenase
      activity of motoneurons in the soleus motor pool were similar in control and
      hindlimb suspended rats. In contrast, compared to control the mean fiber size of
      each fiber type and the percentages of Type I fibers decreased and of Type IIa
      fibers increased in the soleus muscle following hindlimb suspension. CONCLUSIONS:
      The results indicate that significant alterations in the phenotype and size of
      muscle fibers can occur without concomitant adaptations in the innervating
      motoneurons usually associated with motor unit types (i.e., soma size and
      oxidative capacity).

PMID- 9143754
TI  - Comparison of acceleration subjects to other populations: spinal anomaly
      distribution.
AB  - Two Armstrong Laboratory (AL) human volunteer subject panels (sustained and
      impact acceleration) at Wright Patterson AFB, OH, were compared to each other and
      to other samples of different populations in terms of spinal anomalies. These
      sample populations were obtained from the scientific literature: French,
      Norwegian, Netherlands, and U.S. pilots; U.S. Air Force (AF) and Navy subjects,
      and from representative "normal" civilian populations, and then compared using
      the proportion parameters for various spinal anomalies. There were only a few
      common parameters between the two panels and between each panel compared with the
      foreign military, human subjects, and "normal" population. However, there were
      two to six times as many similar spinal anomaly incidence rates between the AL
      panels and the U.S. pilot sample. It was reassuring that the AL subject panels
      used in AF acceleration research have more in common with AF pilots than other
      populations in regards to spinal anomalies, even though the pilot sample may not
      be representative of the true pilot population. Recommendations are to establish
      a common reference point in nomenclature and description of spinal anomalies
      (modeled after the French) and to start collecting spinal radiographs on all U.S.
      pilots. These radiographs would not be for screening but for establishing a
      database following the occupational pathology of flying. This data would also
      facilitate comparisons with research acceleration panels, as well as with foreign
      air forces. Informed decisions can then be made regarding screening criteria for
      the future as aircraft and ejection seat performance envelopes continue to
      expand.

PMID- 9143755
TI  - Passenger safety, health, and comfort: a review.
AB  - Since the birth of aviation medicine approximately 80 yrs ago, practitioners and
      scientists have given their attention primarily to flight deck crew, cabin crew,
      and ground support personnel. However, in more recent years we have broadened our
      horizons to include the safety, health, and comfort of passengers flying
      commercial aircraft. This will be even more compelling as more passengers take to
      the air in larger aircraft and flying longer hours to more distant destinations.
      Further, we can expect to see more older passengers because people in many
      countries are living longer, healthier lives. The author first discusses the
      stresses imposed by ordinary commercial flight upon travelers such as airport
      tumult, barometric pressure changes, immobility, jet lag, noise/ vibration, and
      radiation. Medical considerations are next addressed describing inflight illness
      and medical care capability aboard U.S. air carriers. Passenger safety, cabin air
      quality, and the preventive medicine aspects of air travel are next reviewed in
      the context of passenger safety, health, and comfort. Recommendations are
      addressed to regulator agencies, airlines aircraft manufacturers, and the
      aerospace medicine community.

PMID- 9143756
TI  - Prediction of survival time at sea based on observed body cooling rates.
AB  - The prediction of survival time (ST) of individuals stranded at sea is
      particularly difficult since reliable controlled data are unavailable. An
      individual's rate of body cooling is governed by the difference between heat loss
      and heat production. It has been suggested that the rate of deep body cooling can
      be extrapolated to estimate ST. The observed linearity of this cooling rate
      against water temperature is consistent with the predictions of an independently
      developed mathematical model of ST. This model has been extended to simulate
      conditions of partial immersion and wet clothing, and subsequently calibrated
      against observed human cooling rates. The resultant modification allows a much
      broader range of ST predictions involving calm and rough seas, and non-immersion
      wet conditions. Predictions are presented for lean vs. fat individuals, a "worst"
      case scenario where shivering is absent, and partial immersion. While these
      predictions must be considered speculative and subject to change as better
      information becomes available, the model can be useful as a decision aid. It
      would be prudent, however, to consider the predictions in a relative vs. absolute
      sense; i.e., for comparative purposes.

PMID- 9143757
TI  - Stent recoil: comparison of the Wiktor-GX coil and the Palmaz-Schatz tubular
      coronary stent.
AB  - Wiktor-GX coil stents and Palmaz-Schatz 154A tubular stents were implanted in a
      consecutive series of 40 patients and 45 arteries undergoing successful primary
      stent placement in de novo lesions treated with single stents in order to compare
      the acute recoil of a coil stent to a tubular stent in native coronary arteries.
      Acute stent recoil was determined by measuring the difference between the maximum
      inflated diameter of the stent deployment balloon and the minimum lumen diameter
      after stent deployment. There was no difference between the two groups for
      reference vessel diameter, nominal balloon diameter, maximum inflated balloon
      diameter, maximum inflation pressure, or poststent vessel minimum lumen diameter.
      Acute recoil averaged 0.15 +/- 0.2 mm for the Wiktor-GX and 0.13 +/- 0.1 for the
      Palmaz-Schatz (P = 0.58). In this series of patients, there was no significant
      difference between the acute recoil of the coil stent compared to the tubular
      stent.

PMID- 9143758
TI  - Comparison of clinical complications, angiographic results, and device usage of
      coronary angioplasty using low- and high-compliance balloons.
AB  - We randomized 800 patients in a prospective study comparing the angiographic
      results, device usage and in-hospital outcome of balloon angioplasty of primary
      stenoses of native coronary vessels with low-compliant and highly compliant
      balloons. The cumulative incidence of prespecified clinical endpoints was 8.0% in
      both treatment groups. The primary angiographic success rates were 83.9% and
      78.9% in the high- and low-compliance group, respectively (P = 0.05). For the
      lesions dilated with one study balloon only, the quantitative angiographic
      findings were virtually identical in the two treatment groups. The total number
      of dissections was slightly but not significantly higher in the lesions treated
      with a highly compliant balloon. The global usage of angioplasty balloons was
      similar in both treatment groups. We conclude that, in general, there is no
      objective reason to prefer one balloon material to another on the basis of its
      compliance characteristics.

PMID- 9143759
TI  - Conquering compliance.

PMID- 9143760
TI  - Bailout coronary stenting without anticoagulation or intravascular ultrasound
      guidance: acute and six-month angiographic results in a series of 120 consecutive
      patients.
AB  - The purpose of this study was to evaluate the feasibility, safety, and efficacy
      of bailout coronary stenting without anticoagulation or intravascular ultrasound
      guidance in patients with acute or unequivocal threatened closure after
      conventional angioplasty. One hundred twenty consecutive patients were
      prospectively enrolled according to the following criteria: 1) acute or
      threatened closure after balloon angioplasty; 2) reference vessel diameter > or =
      2.5 mm. All patients after stent implantation were on antiplatelet treatment with
      aspirin and ticlopidine. Four types of stents were used: Palmaz-Schatz (J&J),
      Gianturco-Roubin (Cook), Freedom (Global Therapeutics), and Microstent (AVE).
      Procedural results: a total of 206 stents were implanted in 134 target lesions
      with a stent deployment success rate of 100%; 44 target lesions were treated with
      multiple stent implantation; the mean luminal diameter after stenting was 3.14 +/
      0.34 mm, and the mean final percent diameter stenosis was -2 +/- 10%; the mean
      balloon to vessel ratio was 1.11 +/- 0.15; the mean final pressure inflation was
      13.9 +/- 2.4 atm; an optimal angiographic result was achieved in 128 lesions
      (96%). In-hospital results: in-hospital recurrent ischemia occurred in 4 patients
      (3%); recurrent ischemia resulted directly in death in 1 patient, in nonfatal Q
      waves infarction in 2 patients, and in emergency coronary artery surgery in 1
      patient. Six-month clinical follow-up results: event free survival rate was 77%;
      1 patient had non fatal infarction; the incidence of repeat revascularization
      procedures was 19%; there were no cardiac deaths. Angiographic follow-up results
      (follow-up rate 93%): the restenosis or reocclusion rate was 28%. Bailout
      coronary stenting without chronic anticoagulation treatment or intravascular
      ultrasound guidance may be considered a highly feasible and safe treatment for
      acute or threatened closure after failed angioplasty.

PMID- 9143761
TI  - Friction-free stenting.

PMID- 9143762
TI  - Left main intervention revisited: early and late outcome of PTCA and stenting.
AB  - We reviewed our experience with 28 unselected, consecutive patients undergoing
      left main coronary artery (LMCA) angioplasty who had been considered unsuitable
      for coronary artery bypass graft surgery (CABG). Fourteen patients (50%) had a
      protected LMCA circulation. Balloon angioplasty was performed in 11 patients
      (39.3%), and stents were implanted in 17 patients (60.7%). The procedure was
      elective in 22 patients (78.6%) and acute in the setting of myocardial
      infarction/cardiogenic shock in 6 (21.4%). The mean follow-up duration was 15.9
      +/- 12 months. There were 5 early (before hospital discharge) and 4 late deaths
      (total 32.1%), 1 myocardial infarction (3.6%), 6 repeat angioplasties (21.4%),
      and 3 subsequent CABG (10.7%). All 5 early deaths occurred in patients with
      cardiogenic shock and unprotected circulation. The results of our study suggest
      that when patients have prohibitive surgical risks, elective LMCA angioplasty
      and/or stenting may be undertaken with a high procedural success rate. However,
      our data do not support intervention in the presence of acute myocardial
      infarction/cardiogenic shock.

PMID- 9143763
TI  - Left main coronary angioplasty: is the Bastille of bypass surgery about to go
      down?

PMID- 9143764
TI  - Exaggerated luminal loss a few minutes after successful percutaneous transluminal
      coronary angioplasty in patients with recent myocardial infarction compared with
      stable angina: an intracoronary ultrasound study.
AB  - This study investigates the mechanisms of exaggerated acute luminal loss after
      successful coronary angioplasty in patients with recent myocardial infarction
      compared with stable angina by angiography and intracoronary ultrasound (ICUS).
      We studied 15 consecutive patients (group 1) who, after a successful thrombolysis
      for myocardial infarction, underwent delayed (8 +/- 2 days after the myocardial
      infarction) successful balloon coronary angioplasty. Group 1 patients were
      individually matched with 15 stable angina patients (group 2). The percentage of
      stenosis and acute luminal loss were measured by quantitative coronary analysis.
      The ultrasound characteristics of lumen pathology were described as soft, hard,
      calcified, eccentric, concentric, thrombotic, and dissection lesions. Matching by
      stenosis location, reference diameter, sex, and age resulted in 2 comparable
      groups of 15 lesions with identical baseline characteristics. Immediately after
      percutaneous transluminal coronary angioplasty (PTCA), the minimal luminal
      diameter increased from 0.5 +/- 0.3 mm to 2.4 +/- 0.3 mm and from 0.5 +/- 0.2 mm
      to 2.4 +/- 0.3 mm in groups 1 and 2, respectively. Similar balloon sizes were
      used in both groups. The acute luminal loss (the difference between the maximal
      dilated balloon diameter and the minimal luminal diameter) immediately after PTCA
      was 0.4 +/- 0.2 mm and 0.3 +/- 0.3 mm (14 +/- 8% and 10 +/- 11% of balloon size)
      (P = not significant [NS]) in groups 1 and 2, respectively. After ICUS (mean 24
      min after the last balloon deflation), the acute luminal loss was 0.9 +/- 0.3 mm
      and 0.5 +/- 0.4 mm (29 +/- 11% and 17 +/- 8% of balloon size) (P = 0.01) in
      groups 1 and 2, respectively. There was a significantly higher prevalence of
      intracoronary thrombus formation as detected by ICUS in group 1 compared with
      group 2 (80% vs. 20%; P < 0.001). In matched groups of successfully treated
      coronary angioplasty, patients with recent myocardial infarction had a similar
      magnitude of acute gained luminal loss immediately after the procedure. However,
      an exaggerated luminal loss a few minutes after the last balloon deflation in
      patients with recent myocardial infarction was noted because of mural thrombus
      formation compared with patients with stable angina.

PMID- 9143765
TI  - Comparison of bailout versus elective stenting: time to reassess our benchmarks
      of outcome.
AB  - The aim of this study was to compare the clinical outcome of elective and bailout
      stenting in an era of improved stent deployment techniques and antithrombotic
      therapy. We retrospectively analysed 136 consecutive patients undergoing stent
      implantation over a 15 mo period. There was no significant difference in the
      follow-up duration, length of hospital stay, or the total incidence of major
      complications between the two groups. Bailout stenting, as compared to elective
      stenting, was not associated with an increased incidence of in-hospital (no death
      vs. 1.4%, 4.6% non-Q myocardial infarction vs. 0%, 7.7% vascular complications
      vs. 7.0%) or late complications (no death vs. 1.4%, no non-Q myocardial
      infarction vs. 2.8%, 3.1% repeat angioplasty vs. 5.6%, 1.5% coronary artery
      bypass surgery vs. 1.4%). Stents can be implanted in cases of failed angioplasty
      with a success rate similar to that of elective stent implantation with a low
      incidence of complications and equivalent clinical outcome.

PMID- 9143766
TI  - Plaque rupture as a cause of apparent coronary aneurysm formation following
      directional coronary atherectomy.
AB  - Late coronary aneurysm formation was observed following treatment by directional
      coronary atherectomy. Intravascular ultrasound disclosed that the mechanism
      involved was plaque rupture. The cause of coronary aneurysm may be multifactorial
      after coronary interventions. Intravascular ultrasound imaging is useful for
      understanding the pathologic mechanism of coronary aneurysm production.

PMID- 9143767
TI  - Obliteration of a coronary artery aneurysm with percutaneous transluminal
      coronary angioplasty and stent placement.

PMID- 9143768
TI  - Greenfield filter caval perforation causing an aortic mural thrombus and femoral
      artery occlusion.
AB  - A 32-year-old woman suffered a right femoral artery embolic occlusion from an
      abdominal aortic mural thrombus associated with caval perforation by a stainless
      steel Greenfield Filter. The complication required thrombolytic therapy, surgical
      revascularization, and long-term anticoagulation.

PMID- 9143769
TI  - Transcatheter alcohol ablation of the septum in a patient of hypertrophic
      obstructive cardiomyopathy.
AB  - We performed transcatheter alcohol ablation of the septum in a case of
      hypertrophic obstructive cardiomyopathy. The patient showed marked reduction in
      LVOT gradient; however, he developed complete atrioventricular (AV) dissociation
      following the procedure, requiring AV sequential pacing. This important
      complication of this novel technique is highlighted.

PMID- 9143770
TI  - Coronary artery perforation with subepicardial hematoma.
AB  - Coronary artery perforation is a relatively rare complication in coronary
      angioplasty. We report the case of a 71-year-old male, who was salvaged by
      emergency surgery, for cardiogenic shock due to subepicardial hematoma associated
      with balloon angioplasty. Such a case has not yet previously been reported.

PMID- 9143771
TI  - New technique using temporary balloon occlusion for transcatheter closure of
      patent ductus arteriosus with Gianturco coils.
AB  - We describe our early experience with a new technique involving temporary balloon
      occlusion for transcatheter closure of patent ductus arteriosus (PDA) using
      single or multiple Gianturco coils. Coil occlusion was attempted in 21 patients
      of median age 3 (range 1-11) years, and angiographic PDA diameter 3.0 mm +/- 0.87
      mm. The inflated balloon of a pulmonary wedge pressure catheter over a
      transductal wire was used to mechanically hold the first extruded loop of the
      coil at the pulmonary end of the duct. If a residual shunt persisted after the
      delivery of the first coil, additional coils were delivered with or without the
      balloon support. One to nine coils (median 2) of different sizes varying between
      3-12 mm diameter and 4-15 cm length were used. Immediate angiographic occlusion
      rate was 47.6%. However color Doppler (CD) at 24 hours and at 6 weeks revealed
      complete closure in 66.6% and 80.9%, respectively. Blood transfusion was required
      in 2 (9.5%) patients. Three out of 56 coils (5.4%) embolized during deployment.
      The use of balloon occlusion is effective and safe in the treatment of ducti up
      to 4.7 mm. Residual shunts lend to occlude with time.

PMID- 9143772
TI  - Coronary implantation of silicone-carbide-coated Palmaz-Schatz stents in patients
      with high risk of stent thrombosis without oral anticoagulation.
AB  - Coronary stenting in bail-out situations is effective but associated with
      increased stent thrombosis and bleeding rates. Silicone-carbide coating reduces
      fibrinogen activation on alloplastic surfaces and thus may also reduce stent
      thromboses. A total of 44 patients received 58 silicone-carbide-coated stents for
      threatened (80%) or abrupt (20%) closure. In addition to heparin, patients were
      treated with aspirin and ticlopidine (75%) or aspirin (25%) only. Two patients
      (4.5%) died in the hospital. The combined in-hospital complication rate including
      death, emergency revascularization, stent-related myocardial infarction, and
      stent thrombosis was 9% (4 of 44 patients). Major bleeding occurred in 4 patients
      (9%). Six-month follow-up angiography was obtained in all eligible patients (42
      of 44), revealing a restenosis rate of 21% (9 of 42). Thus, coronary implantation
      of silicone-carbide-coated stents is feasible in bail-out situations without oral
      anticoagulation and with a low complication rate. Further studies are required to
      optimize the anticoagulation regimen with this type of coating.

PMID- 9143773
TI  - Reduction of femoral artery bleeding post catheterization using a collagen
      enhanced fibrin sealant.
AB  - As the number of cardiac catheterization procedures increases, so do associated
      complications and costs. This study suggests that the application of a new
      collagen enhanced fibrin sealant, Collaseal, may be used effectively to achieve
      rapid hemostasis at the arterial puncture site following femoral artery
      catheterization. Results in nine dogs anticoagulated with heparin (activated
      clotting time 396 +/- 107, mean +/- S.D.) revealed a statistically significant
      reduction in signs of gross bleeding in the sealant-treated groins as compared to
      control (2 versus 9, P = .0156). These results indicate that this commercially
      produced sealant might be used in human patients undergoing cardiac
      catheterization to decrease complications, lengths of stay, and costs.

PMID- 9143774
TI  - Temporary arterial stenting: comparison to permanent stenting and conventional
      balloon injury in a rabbit carotid artery model.
AB  - The objective was to assess the arterial wall response to temporary stenting with
      a removable nitinol stent in comparison with permanent stenting and balloon
      injury at 28 days in the rabbit carotid artery. Restenosis remains an important
      limiting factor after the implantation of permanent metallic stents and balloon
      angioplasty. We have developed a temporary nitinol stent that uses a bolus
      injection of warmed saline to collapse the stent for percutaneous removal.
      Vascular changes related to the thermal saline bolus injection required to remove
      a nitinol implanted stent were assessed in 12 rabbit carotid arteries at 7 and 28
      days postinjection. Nitinol stents, inflated to 3.0 mm diameter, were implanted
      for 3 days (n = 6) and histology and quantitative histomorphometry examined at 28
      days. Results were compared with permanently implanted stents (n = 5) and balloon
      injury (n = 9). Dual bolus injection of 10 ml at 70 degrees C created an acute
      necrotizing injury and chronic neointimal proliferation, whereas injections of 5
      ml at 63 degrees C were minimally injurious. Temporary stenting resulted in the
      least neointimal proliferation measured by the intima to media ratio (0.22 +/-
      0.10 vs. 1.59 +/- 0.31 for permanent stenting and; 0.49 +/- 0.14 for balloon
      injury; P < 0.001). Temporary stenting maintained a significantly larger lumen
      than balloon (1.53 +/- 0.72 mm2 vs. 0.64 +/- 0.14 mm2; P < 0.001), which could
      not be explained by absolute changes in intimal cross sectional area (0.14 +/-
      0.07 mm2 vs. 0.21 +/- 0.06 mm2 respectively; P = 0.33). Temporary stenting
      resulted in a relatively larger vessel area within the external elastic lamina
      than with balloon (2.28 +/- 1.06 mm2 vs. 1.30 +/- 0.18 mm2; P = 0.007). The
      thermal stent recovery process can create necrotizing vascular injury and
      neointimal proliferation at higher temperatures and injectate volumes. Stent
      removal after 3 days using 63 degrees C saline bolus injection results in less
      neointimal proliferation than with permanent stents or balloon injury. In
      comparison to balloon injury, temporary stenting also may have a long-lasting
      beneficial effect on vessel recoil and remodeling, resulting in larger lumen size
      after stent removal.

PMID- 9143775
TI  - Stent--who started it?

PMID- 9143776
TI  - Pullback atherectomy for the treatment of intrastent restenosis.

PMID- 9143777
TI  - New insights into vascular reactivity: from altered structure to neural control.
AB  - 1. The present review covers two aspects of the author's research into the
      pharmacology of vascular reactivity of isolated vessels and in the intact
      circulation. First, how 'normal' reactivity is altered by injury or disease and,
      second, how novel drugs have allowed insight into the role of the cotransmitter
      neuropeptide Y and 'N' type calcium channels in neurotransmitter release. 2.
      Acute endothelium removal in the femoral artery of the anaesthetized dog
      confirmed the obligatory role of these cells in the dilatation response to intra
      arterial acetylcholine (ACh). After 4 weeks, conduit arteries respond with a
      thickened neointima following acute endothelial injury but, provided macrophage
      derived foam cells are absent, the artery relaxes normally to ACh. 3. In the dog
      coronary vasculature, stable collateral arteries have a marked neointima of non
      contractile smooth muscle cells that are lined with endothelium. Reactivity to
      vasodilator stimuli is normal while that to vasoconstrictor stimuli is impaired.
      4. In the conscious rabbit, superficial femoral artery (SFA) occlusion stimulates
      profound angiogenesis but, despite these changes to the hindlimb vasculature,
      reactivity to vasodilator and vasoconstrictor agents from day 1 to 6 months
      following SFA is unaltered. 5. Endothelial dysfunction is discussed in relation
      to hypertension, hypercholesterolaemia and congestive heart failure. 6. The novel
      "N' type calcium channel antagonist omega-conotoxin GVIA, was used to explore the
      role of "N' type channels in cardiac and vascular neurotransmitter release in
      conscious rabbits. 7. The novel putative Y 1-selective neuropeptide Y antagonist
      1229U91 was shown to inhibit nerve-mediated contractions of isolated mesenteric,
      but not femoral, artery segments in the rat. This regional difference in a
      possible cotransmitter role of the peptide is discussed.

PMID- 9143778
TI  - Effect of genotype on the angiotensin-converting enzyme mRNA level in human
      atria.
AB  - 1. To clarify the mechanism of the association between I/D polymorphism of the
      angiotensin-converting enzyme (ACE) gene and various cardiovascular disease, ACE
      mRNA levels in human atrial appendages were assessed in relation to the genotype
      of the ACE gene. 2. Angiotensin-converting enzyme mRNA levels were positively
      correlated with age and tended to show a positive correlation with mean pulmonary
      pressure (mPA). Multiple regression analysis indicated that age and mPA, but not
      the genotype of the ACE gene, were predictors of ACE mRNA levels in human atrial
      appendages. 3. The present study indicates that I/D polymorphism of the ACE gene
      is not simply reflected in ACE mRNA levels and that further study is needed to
      determine the mechanism of the association between this polymorphism and various
      cardiovascular diseases.

PMID- 9143779
TI  - Angiotensin II receptors and renin in the porcine uterus: myometrial AT2 and
      endometrial AT1 receptors are down-regulated during gestation.
AB  - 1. The aim of the present study was to characterize the angiotensin II (AngII)
      receptor subtypes in the porcine uterus and the variation of receptor densities
      and renin concentrations during gestation. 2. In myometrium from non-pregnant
      sows, the AngII receptors were almost exclusively AT2 receptors. During
      gestation, the AngII receptor density was decreased and the AT1 receptor became
      predominant in the last part of gestation as a result of a down-regulation of the
      AT2 receptor. 3. In the endometrium, the AT1 receptor was predominant both in non
      pregnant sows and throughout gestation. The AngII receptor density was decreased
      during gestation as a consequence of down-regulation of the AT1 receptor. 4. The
      renin concentrations in the myometrium and endometrium of pregnant sows did not
      differ from those in non-pregnant animals. 5. The finding of enzymatically active
      renin and high densities of AngII receptors in the porcine uterus is in
      accordance with a functional renin-angiotensin system (RAS), which may be
      important for an increased vascular permeability and stimulated angiogenesis in
      early pregnancy and for contraction of the myometrial smooth muscle cells during
      parturition. The predominance of AT1 receptors in the endometrium of non-pregnant
      sows differs from an earlier finding in non-pregnant women, where AT2 receptors
      were predominant in the endometrium. This is in accordance with earlier studies,
      indicating species differences in the expression and possibly also the
      physiological roles of the RAS in reproductive tissues.

PMID- 9143780
TI  - Effect of exercise on plasma adrenomedullin and natriuretic peptide levels in
      myocardial infarction.
AB  - 1. We investigated the effect of exercise on plasma adrenomedullin, atrial
      natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations and
      studied the relationship between these peptides and haemodynamic parameters in
      nine patients with old myocardial infarction (MI) and in eight normal subjects.
      2. The exercise protocol consisted of two fixed work loads (40 and 80 W) for 4
      min each and venous blood samples were taken at rest, during each exercise stage
      and after exercise while monitoring the mean arterial pressure (MAP) and heart
      rate (HR). In MI, pulmonary arterial pressure (PAP), pulmonary capillary wedge
      pressure (PCWP), left ventricular end-diastolic pressure (LVEDP) and cardiac
      output (CO) were measured throughout exercise. 3. Adrenomedullin levels did not
      significantly increase with exercise. Adrenomedullin levels correlated with PAP
      and PCWP at rest (P < 0.05). Atrial natriuretic peptide levels correlated with
      PAP, PCWP and LVEDP throughout exercise (P < 0.05) but, on multiple regression
      analysis, PCWP correlated only with ANP (P < 0.01). Brain natriuretic peptide
      levels correlated with LVEDP throughout exercise (P < 0.01) and its increment
      correlated closely with basal BNP levels at rest (P < 0.01). 4. These results
      suggest that adrenomedullin does not respond to the acute haemodynamic changes of
      exercise, whereas ANP responds to it and PCWP is the major stimulus factor. Brain
      natriuretic peptide responds to exercise in proportion to the basal synthesis of
      BNP in patients with left ventricular dysfunction and LVEDP may play a role in
      increasing BNP during exercise.

PMID- 9143781
TI  - Improving effect of carteolol on bodyweight and carbohydrate and lipid metabolic
      responses in the OLETF rat.
AB  - 1. Carteolol, a non-selective beta-blocker with intrinsic sympathomimetic
      activity, admixed in a pellet diet was administered to Otsuka Long-Evans
      Tokushima Fatty (OLETF) rats, an animal model of spontaneous non-insulin
      dependent diabetes mellitus with mild obesity. A high dose of carteolol (0.02%)
      suppressed bodyweight gain without affecting food and water consumption until the
      appearance of glycosuria. Carteolol tended to reduce the cumulative incidence of
      glycosuria at 26 weeks after the beginning of administration (55, 17 and 25% in
      control rats, and in rats fed a low (0.002%) and high dose of carteolol,
      respectively). 2. At the 26th week of administration, the high dose of carteolol
      decreased visceral fat weight, such as that of retroperitoneal and epididymal
      adipose tissue, whereas the liver and the kidney were not affected. 3. Although
      plasma glucose and triglyceride levels in non-fasted rats were elevated with age,
      carteolol tended to delay the increases in those parameters. Carteolol suppressed
      the increase in plasma glucose levels, which indicate the diabetic pattern, in a
      25th week oral glucose tolerance test. 4. These findings indicate that carteolol
      induces improvements in bodyweight and carbohydrate and lipid metabolism in an
      obese condition. Consequently, carteolol may be useful for the treatment of
      hypertension with obesity in order to prevent cardiovascular events.

PMID- 9143782
TI  - Effects of endurance training on superoxide dismutase activity, content and mRNA
      expression in rat muscle.
AB  - 1. The purpose of the present study was to investigate the changes in superoxide
      dismutase (SOD) isoenzyme (Mn(2+)-SOD and Cu2+, Zn(2+)-SOD) activities, contents
      and mRNA expressions in rat skeletal muscle during endurance training and a
      single bout of exercise. 2. Thirty-eight male Wistar rats were divided into
      untrained (U) and trained (T) groups. The T group rats were treadmill-trained for
      9 weeks. The activity, content and mRNA expression of Mn(2+)-SOD and Cu2+, Zn(2+)
      SOD were determined in the soleus muscle of each rat. 3. Mn(2+)-SOD activity and
      content in the T group were significantly higher than in the U group, both at
      rest (22 and 21%, respectively) and after exercise (24 and 46%, respectively),
      while a single bout of exercise affected neither the activity nor content of
      Mn(2+)-SOD in either group. 4. The content of Cu2+,Zn(2+)-SOD in both groups was
      not different at rest and after exercise, although its activity at rest was
      significantly higher in the T group than in the U group (by 29%). 5. After
      exercise, the expression of Mn(2+)-SOD mRNA was markedly attenuated only in the U
      group (49%); the expression of Cu2+,Zn(2+)-SOD mRNA was not influenced by
      exercise. 6. Our results suggest that adequate endurance training increases both
      the activity and content of Mn(2+)-SOD and that untrained rats are rather
      susceptible to oxidative stress during physical exercise. It thus appears that
      Mn(2+)-SOD provides a reliable index of physical training. 7. The results
      obtained in the present study also suggest that muscle has the capacity of
      responding to training in such a manner as to reduce the potential harm arising
      from the accumulation of oxygen free radicals resulting from enhanced metabolic
      activity.

PMID- 9143783
TI  - Acute effects of oral glibenclamide on blood pressure and forearm vascular
      resistance in diabetics.
AB  - 1. To determine the effects of an acute oral dose of glibenclamide on blood
      pressure (BP), basal forearm vascular resistance (FVR) and FVR responses to the
      K+ATP channel activating vasodilator diazoxide, a placebo-controlled, double
      blind cross-over study was performed in eight male volunteers with non-insulin
      dependent diabetes mellitus. 2. Changes in vascular responses to progressively
      increasing concentrations of diazoxide (3.75-30 mg/kg per min) and noradrenaline
      (25-100 ng/kg per min) were measured by venous occlusion plethysmography. 3.
      Glibenclamide significantly lowered plasma glucose levels compared with placebo
      (P < 0.02) and attenuated the decrease in FVR (P < 0.05) and the decrease in
      systolic BP (P < 0.05) that followed a meal. However, vasodilator responses to
      diazoxide were potentiated by the administration of oral glibenclamide (P <
      0.01). 4. Acute administration of oral glibenclamide attenuates the normal
      decrease in FVR and systolic BP that follows a meal and potentiates rather than
      inhibits forearm vasodilator responses to intra-arterial diazoxide, probably via
      indirect humoral effects. These results suggest that glibenclamide has direct or
      indirect vasoconstrictor effects that antagonize the normal increase in forearm
      blood flow that follows a meal and that the inhibition of vascular K+ATP channels
      following acute oral glibenclamide administration is clinically insignificant
      compared with other indirect vascular effects of the drug.

PMID- 9143784
TI  - Effects of one-clip, one-kidney hypertension in chronically catheterized pregnant
      ewes.
AB  - 1. Hypertension secondary to renal disease was studied in non-pregnant and
      pregnant ewes to determine whether there were any changes in arterial pressure
      and the distribution of cardiac output and, in particular, whether uteroplacental
      blood flow was affected. 2. In six non-pregnant, chronically catheterized,
      uninephrectomized ewes, a reduction in renal blood flow (RBF) to 40-50% of
      control caused hypertension within 3 h. This was maintained for as long as RBF
      was reduced (72 h) and returned to control 24 h after the occluder around the
      renal artery was released. When this experiment was repeated in 16
      uninephrectomized pregnant ewes (118-134 days gestation) hypertension occurred
      within 3 h and was sustained for as long as RBF was reduced (between 24 and 72
      h). Arterial pressure returned to control within 24-72 h of restoring RBF. 3.
      Compared with non-pregnant ewes, pregnant ewes had similar arterial pressures,
      higher cardiac outputs (CO; P < 0.001) and heart rates (HR; P < 0.001), lower
      total peripheral resistances (TPR; P < 0.001) and similar blood flows to brain,
      ovary, pancreas, kidney and spleen. Splenic vascular resistance (VR) was greater
      (P = 0.006), gut blood flow was greater (P < 0.05) and gut VR was less (P <
      0.05). Myoendometrial blood flow/g was greater (P < 0.005) and myoendometrial VR
      was less (P = 0.006). 4. In pregnant sheep with renal clip hypertension, there
      was no change in CO and HR, but TPR increased (P < 0.01), as did plasma renin
      activity. Gut, brain, pancreatic and myoendometrial VR were increased as long as
      RBF was reduced; in addition, myoendometrial VR remained high for the rest of the
      experiment. Placental blood flow was unchanged at 3 h; 24-72 h later it was
      reduced (P < 0.05) and remained low. Placental VR was increased 24-72 h after RBF
      was restored when ewes were again normotensive. 5. Thus, one-clip, one-kidney
      renal hypertension in the pregnant ewe was due to increased TPR associated with a
      fall in uteroplacental blood flow that persisted even when RBF was restored and
      ewes were normotensive. This reduction in uteroplacental blood flow could account
      for the high foetal morbidity and mortality that occurs in pregnant women with
      renovascular hypertension.

PMID- 9143785
TI  - Nitric oxide deficiency induces myocardial infarction in hypercholesterolaemic
      stroke-prone spontaneously hypertensive rats.
AB  - 1. To observe the effect of nitric oxide (NO) on the myocardium, the NO synthesis
      inhibitor NG-nitro-L-arginine (L-NNA) was administered to hypercholesterolaemic
      stroke-prone spontaneously hypertensive (SHRSP) rats. 2. Hypercholesterolaemic
      SHRSP were produced by feeding SHRSP a high fat and high cholesterol diet (HFC)
      for 2 weeks. The rats were then divided into three groups: (i) the N group, which
      were fed the HFC diet containing 0.023% L-NNA and 1% NaCl in their drinking water
      (n = 10); (ii) the NH group, which were fed the HFC diet containing 0.023% L-NNA
      and 1% NaCl in their drinking water which also contained 80 mg/L hydralazine (n =
      10); and (iii) the C group, which were fed the HFC diet and 1% NaCl in their
      drinking water (n = 10). 3. All rats in the N and NH groups died within 35 days
      of the initiation of L-NNA administration. Rats in the N and NH groups had
      significantly increased serum creatine phosphokinase, lactate dehydrogenase,
      glutamic oxaloacetic transaminase and serum total cholesterol levels compared
      with rats in the C group. 4. Fibrosis in response to necrosis was
      histopathologically observed in the hearts of all rats in the N and NH groups
      without exception. Occlusion or intimal thickening in the arteries adjacent to
      the necrotic regions was also observed. 5. These results suggest that nitric
      oxide deficiency induces myocardial infarction in hypercholesterolaemic SHRSP.
      These NO-deficient hypercholesterolaemic SHRSP offer a new model of myocardial
      infarction in rats.

PMID- 9143786
TI  - Non-specific inhibitors of nitric oxide synthase cause myocardial necrosis in the
      rat.
AB  - 1. To study the effect of acute nitric oxide (NO) inhibition on the rat heart
      both in vitro and in vivo, male Wistar rats received a single bolus injection of
      saline, N omega-nitro-L-arginine methyl ester (L-NAME; 0.5, 1.5, 5.0, 15.0 and
      45.0 mg/kg) and D-NAME (45.0 mg/kg). 2. Animals were killed 72 h after the bolus
      injection of L-NAME and the hearts were removed and studied under light
      microscopy. In other groups of animals; saline, L-NAME and D-NAME were
      administered as above and the mean arterial blood pressure (MABP/carotid) was
      recorded. Furthermore, L-NAME was also administered in the drinking water (20
      mg/kg per day) for 72 h and animals were then killed and their hearts evaluated
      as described above. Hearts of control animals were perfused in vitro and coronary
      flow was measured following saline, L-NAME (45 micrograms/heart) and D-NAME (45
      micrograms/heart). 3. Areas of necrosis were observed in the left ventricle of
      animals that had received L-NAME at 5.0, 15.0 and 45.0 mg/kg. Also, only doses
      higher than 1.5 mg/kg caused an important increase in MABP. The frequency and
      extent of the lesions paralleled the dose of L-NAME administered and no lesions
      were observed in D-NAME- and saline-treated animals. 4. The oral administration
      of L-NAME also caused myocardial lesions similar to those described above, but
      the frequency and extent of these lesions were more discrete compared with those
      observed following 5.0 mg/kg, i.v., L-NAME. 5. Bolus injection of L-NAME into
      control rat hearts in vitro resulted in a small and transient fall in coronary
      flow (17.2 +/- 1.4 and 12.2 +/- 1.2 mL/min before and after L-NAME
      administration, respectively) within 30 s and this was followed 4.5 min later by
      a further (11.5 +/- 1.6 mL/min) decrease. The administration of D-NAME to control
      hearts caused no change in coronary flow. 6. In conclusion, the acute inhibition
      of NO biosynthesis by L-NAME causes myocardial necrosis. Both high levels of MABP
      and a small but significant reduction in coronary flow (associated or not) can be
      responsible for the lesions we found.

PMID- 9143787
TI  - Renal regulation of phosphate excretion in endotoxaemic rats.
AB  - 1. Maintenance of phosphate homeostasis is essential for energy producing and
      oxygen delivery systems, particularly, when the energy requirements are increased
      in certain conditions, such as septicaemia. We investigated the phosphaturic
      response to parathyroid hormone (PTH) in endotoxin (ETx)-treated rats in order to
      clarify the renal regulation of phosphate excretion during endotoxaemia. 2.
      Wistar rats that had undergone thyroparathyroidectomy were challenged with either
      Escherichia coli ETx (n = 8) or saline vehicle (n = 9). Thirty-minute renal
      clearance tests were done before and after PTH infusion. Rats infused with saline
      instead of PTH served as time controls for the ETx- (n = 7) and saline-treated (n
      = 8) rats. 3. In time control rats, ETx administration enhanced phosphate
      excretion progressively and this was associated with an obvious increase in the
      level of kidney adenosine 3', 5'-cyclic mono-phosphate (P < 0.005) compared with
      levels following saline vehicle administration. However, this phosphaturia in
      late-phase endotoxaemia was not observed in rats infused with PTH; ETx, but not
      saline vehicle, blunted the PTH-mediated increase in phosphate excretion (P <
      0.005). Increased urinary noradrenaline and constant dopamine excretion were
      observed in endotoxaemic rats. Endotoxin administration produced marked metabolic
      acidosis and hypocapnia in comparison with the administration of the saline
      vehicle. 4. To test whether renal tubular sensitivity to parathyroid hormone
      related-protein (PTHrP) was enhanced during endotoxaemia, phosphaturic response
      to PTHrP in ETx- (n = 7) and saline-treated rats (n = 7) was examined.
      Parathyroid hormone related-protein infusion produced phosphaturia in both
      groups. However, the severity of the phosphaturia after PTHrP infusion was less
      in ETx-than in saline-treated rats. 5. In summary, although ETx administration
      causes a progressive increase in phosphate excretion in the absence of PTH, this
      is overcome by the antiphosphaturic effect of ETx, attenuating PTH-mediated
      phosphaturia after PTH infusion.

PMID- 9143788
TI  - Concentration-effect relationships of morphine and morphine-6 beta-glucuronide in
      the rat.
AB  - 1. The aims of the present study were to determine the relationship between the
      antinociceptive effect and concentrations of morphine and morphine-6 beta
      glucuronide (M6G) in plasma and in the brain. 2. Morphine (14.0 and 28.0
      mumol/kg) or M6G (8.67 and 17.3 mumol/kg) were administered s.c. to male Hooded
      Wistar rats. The antinociceptive effect was measured by the thermal tail-flick
      method at various times up to 2 h and concentrations of morphine, morphine-3 beta
      glucuronide (M3G) and M6G in plasma and in the brain were determined. 3. With a
      two-fold increment in morphine dose, the areas under the antinociceptive effect-,
      plasma morphine concentration- and brain morphine concentration-time curves
      increased by 1.9-, 2.3- and 2.3-fold, respectively. The area under the plasma M3G
      concentration-time curve increased 2.7-fold. Morphine-6 beta-glucuronide was not
      detected in any sample. For M6G, doubling of the dose led to a 1.7-fold increase
      in the area under the curve for plasma-time M6G concentrations but an 8.7-fold
      increase in the area under the curve for the antinociception-time effect.
      Concentrations of M6G in the brain were below the limit of quantification. The
      relationship between antinociceptive effect and plasma morphine or M6G were
      characterized by counter-clockwise hysteresis loops, probably reflecting a delay
      in crossing the blood-brain barrier. 4. Morphine-6 beta-glucuronide was
      approximately equipotent to morphine on the basis of dose, but substantially more
      potent on the basis of brain concentration.

PMID- 9143789
TI  - Beneficial effects of pentoxifylline on cyclosporine-induced nephrotoxicity.
AB  - 1. Hypertension and renal failure are the two most common and severe
      complications due to cyclosporine A (CsA) therapy after transplantation. To
      determine whether an in vivo treatment with pentoxifylline (PTX) can prevent the
      toxic effects of CsA, three groups of rats were studied. 2. The first group of
      rats (n = 11) received daily injections of CsA (15 mg/kg, i.m.) and PTX (45
      mg/kg, i.p., b.i.d.), the second group of rats (n = 11) was treated with CsA only
      and the third group of rats (n = 11) served as the control group (vehicle
      treatment). 3. Whole blood CsA levels were similar in CsA + PTX and CsA alone
      groups. Although CsA treatment significantly increased mean arterial blood
      pressure (110.00 +/- 2.48 mmHg; P < 0.01), there was no significant increase in
      the PTX co-treated group (104.09 +/- 2.96 mmHg) compared with initial values. In
      both the CsA alone and CsA + PTX groups the heart rate (365.45 +/- 6.65 and
      357.27 +/- 7.23 b.p.m., respectively; P < 0.05) were found to be significantly
      higher than initial values. Serum creatinine levels increased significantly in
      the CsA alone group (1.40 +/- 0.11 mg/dL; P < 0.01) compared with control values
      (0.81 +/- 0.04 mg/dL). This increase was prevented by co-treatment with PTX
      (serum creatinine 1.11 +/- 0.01 mg/dL; P < 0.05). Total [99mTc]-DTPA percentage
      renal uptake, as an index of glomerular filtration rate (GFR), was markedly and
      significantly lower in the CsA alone group (10.01 +/- 0.79%; P < 0.01) than in
      the control group (18.19 +/- 1.32%). Pentoxifylline co-treatment attenuated this
      decrease compared with GFR in the CsA alone group (13.00 +/- 0.75%; P < 0.01). 4.
      These results suggest that the co-administration of PTX with CsA may prevent the
      dose-limiting toxic effects of CsA therapy.

PMID- 9143790
TI  - Feasibility of conducting cardiovascular outcome research in Australian general
      practice: results from the ANBP2 pilot study. Australian National Blood Pressure
      Study.
AB  - 1. The present study aimed to determine the feasibility of conducting a 5 year
      cardiovascular outcome trial of the treatment of 6000 elderly hypertensive
      patients in Australian general practices. 2. General practitioners (GPs) were
      invited to participate by mail and personal follow-up. Patient records were
      reviewed to identify subjects for a blood pressure (BP) screening programme.
      Blood pressure was measured on three occasions and eligible subjects were
      included if the average BP was > or = 160 mmHg systolic or > or = 90 mmHg
      diastolic if systolic BP was > or = 140 mmHg. 3. Seven hundred and forty-one GPs
      were approached and 89 were enrolled in the study (12% of mail invites and 75% of
      those receiving a personal contact). In 16 practices where screening was
      completed, 82,000 records were reviewed to identify 4% patients eligible for
      screening. Twenty-two per cent of eligible subjects attended screening. Of 1938
      subjects screened, 180 (9%) had BP > or = 160/90 mmHg. Forty-seven per cent of
      subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were
      withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP
      return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81
      previously treated subjects were randomized (7% of the screened population). 4.
      Based on the high participation rate of GPs, the response rate of patients to
      attend a BP screening programme and the 7% randomization to screening ratio for
      entry into the study, the ANBP2 pilot study has demonstrated that it is feasible
      to recruit subjects from Australian general practices to a cardiovascular outcome
      trial.

PMID- 9143791
TI  - Urodilatin (INN:ularitide) as a new drug for the therapy of acute renal failure
      following cardiac surgery.
AB  - 1. Acute renal failure is a severe complication following major cardiac surgery.
      2. The effects of urodilatin were evaluated in a randomized, double-blind trial
      in patients suffering from incipient acute renal failure following cardiac
      surgery. 3. In the urodilatin group (n = 7) acute renal failure was reverted,
      whereas in the placebo group (n = 7) six patients had to be haemofiltered or
      haemodialysed (P < 0.005). 4. Urodilatin induced a rapid onset of diuresis in
      contrast to placebo-treated patients, who remained oliguric. 5. In the placebo
      group four of seven patients died while still on haemodialysis (mortality rate
      57.1%) during a postoperative follow-up period of 60 days, while all patients
      treated with urodilatin survived. 6. On the basis of these results it would
      appear that urodilatin is an effective drug for the treatment of incipient
      oliguric acute renal failure following cardiac surgery and for avoiding
      haemodialysis/haemofiltration.

PMID- 9143792
TI  - Response to dietary fat and cholesterol and genetic polymorphisms.
AB  - 1. We examined common polymorphisms in the genes encoding the LDL receptor,
      lipoprotein lipase, apoAI, apoB, apoAIV and cholesteryl ester transfer protein
      and related them to changes in LDL and HDL cholesterol after high fat/high
      cholesterol diets. 2. The only significant association was seen with the apoIV
      polymorphism, which leads to a structural change in the protein. The response to
      fat and cholesterol in subjects with at least one apoAIV 2 allele was only 30% of
      that seen in subjects with the common apoIV 1 allele (P < 0.01), accounting for 6
      7% of the variance in response. This confirms the results of two previous studies
      in which dietary cholesterol intake was changed. 3. No association were seen with
      polymorphisms of the other five genes examined.

PMID- 9143793
TI  - Lipid modifying agents: mechanisms of action and reduction of cardiovascular
      disease.
AB  - 1. Recent studies (4S, CARE, WOSCOPS) with the HMG CoA reductase inhibitors have
      shown that reductions of total cholesterol and LDL cholesterol reduce the risk
      for a new fatal or non-fatal cardiac event by approximately 30-35%, providing LDL
      is decreased by 25-35%. 2. Preliminary data also suggest that achieved LDL levels
      around 3.2 mmol/L results in no greater reduction in new events than when LDL is
      lowered even further. 3. There is considerable debate, nonetheless, as to whether
      these reduction in cardiovascular events are entirely a consequence of LDL
      reduction or whether the lipid-modifying agents have effects on lipoprotein
      structure, endothelial cell function, clotting and haemorrheological pathways. 4.
      The study results achieved with statins have obscured the role of fibrates as
      useful agents for reducing cardiovascular disease. Fibrates have a different mode
      of action to stains by reducing triglyceride-rich lipoprotein precursors and
      favourably altering LDL and HDL composition. 5. The practising clinician needs to
      consider the lipoprotein phenotype and to choose whether the ideal treatment is
      stain alone, fibrate alone or perhaps a combination.

PMID- 9143794
TI  - Role of lipid synthesis, chaperone proteins and proteasomes in the assembly and
      secretion of apoprotein B-containing lipoproteins from cultured liver cells.
AB  - 1. Apolipoprotein B (apoB) is necessary for the assembly and secretion of both
      chylomicrons from the small intestine and very low-density lipoproteins (VLDL)
      from the liver. ApoB is also the major protein in low-density lipoproteins (LDL)
      and is the ligand for the LDL receptor. Studies in humans suggest that increased
      production of apoB-containing lipoproteins, particularly VLDL, is a common
      abnormality in dyslipidaemias. 2. Studies in primary and long-term cultures of
      hepatocytes and hepatoma cells indicate that a significant proportion of newly
      synthesized apoB is rapidly degraded and that this is the major mechanism for
      regulation of apoB secretion. The availability of newly synthesized lipids,
      particularly triglyceride and cholesteryl ester, appears to be a critical factor
      in targeting apoB for secretion rather than degradation. 3. ApoB is an atypical
      secretory protein in that cotranslational translocation across the endoplasmic
      reticulum membrane, a feature of all secretory proteins, seems to slow or stop in
      the absence of adequate lipid availability (or in the absence of microsomal
      triglyceride transfer protein), allowing for rapid degradation of apoB. 4. The
      degradation of apoB seems to be facilitated by the association of nascent apoB
      with the major cytosolic chaperone protein, heat shock protein 70. Additionally,
      degradation of nascent apoB appears to occur, to a large degree, via the
      proteasomal pathway for degradation of cytosolic proteins.

PMID- 9143795
TI  - Regulation of leucocyte-endothelial interactions of special relevance to
      atherogenesis.
AB  - 1. The cellular events underlying atherosclerosis include the accumulation of
      lipid-laden monocytes in the neointima. This process is associated with the
      expression of adhesion proteins and chemokines by the endothelium, in a manner
      similar to that seen after the administration of pro-inflammatory cytokines to
      endothelial cells. 2. The processes that limit endothelial responses to
      proinflammatory cytokines are, therefore, the subject of this paper. Evidence is
      presented that the cytokine TGF-beta exerts a tonic inhibitory influence on
      endothelial responses. Furthermore, the smooth muscle cells adjacent to
      endothelial cells have a similar effect to exogenous TGF-beta and this suggests
      that these two cells form a functional interactive unit. Finally, the
      atheroprotective lipid fraction, high-density lipoproteins (HDL), also inhibits
      endothelial activation. The mechanism of effect of HDL that appears separate from
      its traditional role in cholesterol transport may yield novel insights into
      atheroprotection.

PMID- 9143796
TI  - Contact lens-related microbial keratitis: Part II: Pathophysiology.
AB  - The literature is reviewed concerning the pathophysiologic effects of contact
      lens wear, the microbiology of contact-lens wear, the change in microflora with
      contact-lens wear, the contamination of contact lenses and contact-lens products,
      patient compliance, and corneal interaction with the contact lens. Hypoxia and
      hypercapnia are the most significant changes in the cornea as a result of contact
      lens wear. Changes take place in the conjunctival flora in patients with contact
      lenses. Compliance of patients and contamination of contact lenses and contact
      lens products are significant risk factors. The corneal interaction with the
      contact lens can overwhelm the protective mechanisms of the cornea, increasing
      the ability of microbes to adhere to the cornea and progress to microbial
      keratitis. Some of the factors associated with microbial keratitis are modifiable
      and should stimulate the contact-lens industry to develop better contact lenses
      and contact lens products and also permit ophthalmologists to obtain better
      informed consent from their patients.

PMID- 9143797
TI  - Prospective trial of daily and extended wear disposable contact lenses.
AB  - PURPOSE: The current study prospectively evaluates the response to daily and
      extended wear of disposable lenses with each patient acting as his/her own
      control. This paradigm allowed for elimination of individual variation as a
      confounding factor, as well as determining whether an intrinsic factor, other
      than lens wear, predisposed patients to complications. METHODS: One hundred
      thirty-four patients were randomly assigned to contralateral daily wear (DW) or
      extended wear (EW) with Acuvue lenses for 1 year. All lenses were disposed of on
      a weekly basis. Bilateral bacteriology of lids, conjunctivae, lenses, and fingers
      was carried out on those patients presenting with complications. RESULTS: The
      results after 1 year indicate a higher incidence of complications in the EW eye
      (peripheral infiltrative keratopathy, 12%; corneal striae, 3%). No significant
      clinical complications occurred in the DW eye. Microbiological cultures did not
      reveal any significant difference between those eyes with keratopathy and those
      of controls. The most common pathogen was Staphyloccocus epidermidis. No gram
      negative organisms grew from any of the culture sites. CONCLUSIONS: The results
      of this study indicate that extended wearing schedules, and not the lens entity,
      predispose the patient to a higher risk of keratopathy with disposable contact
      lenses. No microbiological association with the adverse events could be
      determined, and no intrinsic patient factor could be demonstrated that would
      predict the likelihood of complications.

PMID- 9143798
TI  - The role of topical corticosteroids in the management of Acanthamoeba keratitis.
AB  - PURPOSE: To clarify the role of topical corticosteroids in the management of
      Acanthamoeba keratitis. METHODS: The records of 38 patients diagnosed with
      Acanthamoeba keratitis at three institutions were retrospectively reviewed.
      RESULTS: After medical therapy alone, patients diagnosed within 1 month of
      symptom onset had an increased likelihood of being cured (p = 0.02) and attaining
      visual acuity of 20/60 or better (p < 0.01). Fourteen (73.7%) of 19 patients
      treated with topical corticosteroids at any time were cured after antiamoebal
      therapy alone, whereas five (26.3%) patients required penetrating keratoplasty
      for either persistent infection (n = 3) or perforation (n = 2). The mean
      antiamoebal therapy duration, excluding duration after keratoplasty if
      applicable, was 38.5 weeks. Thirteen (76.5%) of 17 patients treated with
      antiamoebal therapy without topical corticosteroids were medically cured, whereas
      four (23.5%) required penetrating keratoplasty for either persistent infection (n
      = 2) or perforation (n = 2). The mean antiamoebal therapy duration was 20 weeks.
      Although the mean antiamoebal therapy duration in the steroid-treated group was
      significantly longer than that in the non-steroid-treated group (p = 0.02),
      outcome after medical therapy between the groups was not significantly different.
      CONCLUSIONS: Topical corticosteroids were not associated with a higher rate of
      medical treatment failure in patients with Acanthamoeba keratitis. Rather, poor
      outcome was significantly related to diagnostic delays. Therefore prudent use of
      corticosteroids in selected patients with severe pain not responsive to
      analgesics or severe corneal or anterior chamber inflammation appears justified.

PMID- 9143799
TI  - Topical cyclosporin A in the management of postkeratoplasty glaucoma.
AB  - PURPOSE: To evaluate the effect of substituting topical cyclosporin A 0.5% for
      topical corticosteroids in patients with postkeratoplasty glaucoma. METHODS:
      Topical cyclosporin A 0.5% was prospectively substituted for topical
      corticosteroids to treat 25 patients with postkeratoplasty glaucoma. RESULTS:
      Twenty-one (84%) of 25 patients showed a reduction in intraocular pressure (IOP)
      (range, 1-22 mm Hg; mean, 8.7 mm Hg). Follow-up ranged from 3 to 12 months (mean,
      5.8). Graft clarity was maintained in all patients, with one allograft rejection
      episode. Thirteen patients were able to discontinue one or more glaucoma
      medication(s). CONCLUSION: Topical cyclosporin A 0.5% may be substituted for
      topical corticosteroids to aid in the management of postkeratoplasty patients
      with glaucoma. However, the resultant decrease in IOP may be associated with an
      increased risk for immune rejections.

PMID- 9143800
TI  - Conjunctival impression cytology in patients wearing contact lenses.
AB  - PURPOSE: Evaluation of contact lens-induced cytologic changes on the conjunctival
      surface. METHODS: Fifty eyes of 25 patients wearing soft or rigid gas-permeable
      contact lenses, and 50 healthy eyes of 25 control subjects were examined with
      conjunctival impression cytology. Of the patients wearing contact lenses, 40% did
      not have any contact lens-related complaints, whereas 60% had some minor
      complaints related to contact lens intolerance. The material obtained by
      impression cytology was examined with regard to epithelial cell morphology,
      goblet cell density, and snake-like nuclear chromatin changes. RESULTS: When
      epithelial cell morphology was graded according to the system described by
      Nelson, specimens from the control group revealed 90% of the eyes to be grade 0
      and 10% to be grade 1, whereas of the eyes wearing contact lenses, 8% were grade
      0, 36% grade 1, 32% grade 2, and 24% grade 3. Thus statistically significant
      differences were observed between the control group and the contact lens group
      with regard to each grade (p < 0.05) as well as to the goblet cell densities (p <
      0.05). Snake-like chromatin changes, on the other hand, were observed in 30 and
      27% of the eyes wearing soft and rigid gas-permeable contact lenses,
      respectively, whereas these were not encountered in any eye in the control group.
      CONCLUSION: Epithelial changes were noted to be more frequent and more severe in
      symptomatic patients than in those without any complaints. No correlation was
      found between average duration of contact lens wear and the risk of contact lens
      intolerance or development of squamous metaplasia.

PMID- 9143801
TI  - Mycotic keratitis in children: epidemiologic and microbiologic evaluation.
AB  - PURPOSE: To evaluate the demographic features, clinical profile, and laboratory
      diagnosis in cases of mycotic keratitis in children. METHODS: We retrospectively
      analyzed 211 cases of mycotic keratitis in children younger than 16 years over a
      5-year period in a tertiary eye center. Culture-proven cases of fungal keratitis
      were reviewed. RESULTS: Trauma was the most common predisposing factor (55.3%),
      followed by associated systemic illness (11.2%), previous ocular surgery (9.8%),
      and others. Corneal injury contaminated with vegetable matter was responsible for
      60.5% of traumatic cases. Aspergillus species were the most frequent isolates
      (39.5%). Others included Fusarium (10.7%), Alternaria (10.2%), Curvularia (7.4%),
      and Penicillium (7%). A seasonal variation in the incidence of mycotic keratitis
      revealed a peak incidence in the months of September and October. One hundred
      sixty-two children (76.7%) cooperated for examination and scraping under topical
      anesthesia with or without sedation. General anesthesia for scraping was required
      in 49 (23%) of 211 children for corneal scraping. Gram stains of corneal scraping
      were positive for hyphal elements in 54.5% of cases, and potassium hydroxide wet
      mount preparation was positive in 90.2% of cases. CONCLUSIONS: This study
      highlights important risk factors and organisms responsible for mycotic keratitis
      in children.

PMID- 9143802
TI  - Epithelial growth within the lamellar interface after laser in situ
      keratomileusis (LASIK)
AB  - PURPOSE: To report the occurrence and follow-up of ectopic, interface, epithelial
      growth after laser in situ keratomileusis (LASIK) in four eyes (three patients)
      and provide suggestions for management. METHODS: Each eye was examined by slit
      lamp biomicroscopy, and corneal topography was obtained with the Tomey TMS-1
      instrument. RESULTS: Each eye with epithelium within the interface after LASIK
      developed interface opacities and surface irregularity. One eye had an early
      surgical intervention, and three eyes were observed. Each eye lost at least one
      line of best spectacle-corrected visual acuity and had visual disturbance at the
      last follow-up visit. CONCLUSIONS: The presence of epithelium within the lamellar
      interface is a significant complication after LASIK. In some cases, interface
      epithelium may be associated with early postoperative inflammation. When
      reoperation is required to treat this complication, we suggest scraping of both
      sides of the interface with a metal blade. In some cases, light excimer laser
      treatment can be used to facilitate epithelial removal.

PMID- 9143803
TI  - Keratometric results of penetrating keratoplasty with the Hessburg-Barron and
      Hanna trephine systems using a standard double-running suture technique.
AB  - PURPOSE: To compare final, sutures-out, keratometric results of penetrating
      keratoplasty using two different suction trephine systems and a standard double
      running suture technique. METHODS: Keratometric data after final suture removal
      were compared retrospectively for three groups of transplants: Group 1, 7.50-mm
      Hessburg-Barron recipient trephine and 7.70-mm modified Lieberman donor punch (n
      = 70); Group 2, 7.50-mm Hessburg-Barron recipient trephine and 8.00-mm modified
      Lieberman donor punch (n = 18); Group 3, 7.50-mm Hanna recipient trephine and
      7.75-mm Hanna donor punch (n = 68). RESULTS: Final average keratometry was 46.7
      +/- 2.4 D (mean +/- SD, diopters), and final median keratometric astigmatism was
      4.6 D (2.6-7.4 D, interquartile range), with no significant difference between
      groups. Final average keratometry values increased from preoperative values by
      3.3 +/- 2.7 D. The correlation between preoperative average keratometry values
      and final values was low (rs = 0.2; p = 0.07). Average keratometry values
      increased by 2.3 D (median) after 10/ 0 suture removal (p < 0.0001) and by 0.2 D
      (median) after 11/0 suture removal (p = 0.09), with no significant difference
      between groups. There was a negative correlation between donor age and overall
      change in average keratometry (rs = -0.3; p = 0.002). Visual acuity improved by a
      median of 5 lines, with no significant difference between trephine systems.
      CONCLUSIONS: There was no statistically significant difference in keratometric
      results using these two suction trephines with a standard suture technique. Final
      graft curvature was greater with both suction trephines compared with previously
      published results of transplants using hand-held trephines with the same suture
      technique.

PMID- 9143804
TI  - Corneal endothelial cell density in glaucoma.
AB  - PURPOSE: We studied corneal endothelial cell density in patients with glaucoma.
      METHODS: One hundred two patients with glaucoma were compared with 52 patients
      without glaucoma of the same age group. Exclusion criteria included history of
      either corneal disease, ocular inflammation, trauma, or surgery other than
      peripheral iridectomy. The following data were extracted from the patient files:
      glaucoma type and duration, laser treatments, glaucoma medications, and
      documented intraocular pressure (IOP) measurements. Specular microscopies were
      performed on central corneas, endothelial images were analyzed by computerized
      planimetry, and cell counts were calculated. RESULTS: Corneal endothelial cell
      counts were significantly lower in patients with glaucoma (2,154 +/- 419
      cells/mm2) than in controls (2,560 +/- 360 cells/mm2; t test, p < 0.0001). In the
      glaucoma group, cell counts were inversely proportional to the means of IOPs.
      Patients receiving three or four glaucoma medications had lower cell counts than
      those receiving one or two medications. Cell counts were significantly lower both
      in primary angle-closure glaucoma and in primary open-angle glaucoma. CONCLUSION:
      This study suggests that patients with glaucoma may have lower corneal
      endothelial cell density than those without glaucoma of the same age group. The
      proposed mechanisms are direct damage from IOP, congenital alteration of the
      corneal endothelium in patients with glaucoma, glaucoma medication toxicity, or a
      combination of these.

PMID- 9143805
TI  - Comparison between the refractive results of combined penetrating
      keratoplasty/transsclerally sutured posterior chamber lens implantation and the
      triple procedure.
AB  - PURPOSE: We determined how accurately we could predict the intraocular lens (IOL)
      power for a combined penetrating keratoplasty and transsclerally sutured
      posterior chamber lens implantation procedure (PK/TS-SPCL) compared with the
      Triple procedure (penetrating keratoplasty, extra-capsular cataract extraction,
      and IOL insertion). METHODS: We retrospectively evaluated the postoperative
      refractive results of 27 patients who had undergone PK/TS-SPCL and compared them
      with those of 46 patients who had undergone a Triple procedure. All patients with
      a final visual acuity > 20/50 who had surgery at the University of Minnesota
      between January 1988 and December 1993 were included in this study. RESULTS: The
      mean postoperative deviation from the predicted refractive error was 1.79 D for
      the Triple group and 1.81 D for the PK/TS-SPCL group (p = 0.95). Sixty-three
      percent of the Triple patients and 67% of the PK/TS-SPCL patients were within 
      2.00 D and +2.00 D of their predicted refractive error. As a group, the Triple
      patients had a mean postoperative keratometry reading of 44.64 compared with
      45.58 for the PK/TS-SPCL patients (p = 0.12). CONCLUSION: These results indicate
      that our accuracy in predicting the IOL implant power in PK/ TS-SPCL is quite
      comparable with that obtained for the Triple procedure, and our refractive
      results for each group are quite similar.

PMID- 9143806
TI  - Proteoglycans contain a 4.6-A repeat in corneas with macular dystrophy: II.
      Histochemical evidence.
AB  - PURPOSE: Synchrotron x-ray diffraction experiments indicate that corneas with
      macular corneal dystrophy (MCD) contain unusual 4.6-A periodic repeats thought to
      reside in proteoglycans or glycosaminoglycans. Recently the 4.6-A x-ray
      reflection was found to be significantly diminished after incubation of MCD
      specimens in buffer containing chondroitinase ABC or N-glycanase. We examined the
      sulfated proteoglycans in these glycosidase-digested MCD corneas. METHODS:
      Transmission electron microscopy was used in conjunction with cuprolinic blue
      staining for sulfated proteoglycans. RESULTS: Incubation of an MCD specimen in
      enzyme buffer left both small and large proteoglycan filaments in the stromal
      matrix, whereas incubation in the presence of chondroitinase ABC removed these
      molecules from the tissue. Incubation in buffer containing N-glycanase, on the
      other hand, removed the large proteoglycan filaments from the MCD stroma but left
      unaffected the small collagen-associated proteoglycans. CONCLUSION: These results
      are consistent with the interpretation that 4.6-A periodic repeats in MCD corneas
      reside in large sulfated proteoglycan filaments (or aggregates thereof) that may
      contain chondroitin/dermatan sulfate and keratan sulfate or keratan components.

PMID- 9143807
TI  - Histopathology of the ocular surface after eye rubbing.
AB  - PURPOSE: This study demonstrates the effects of eye rubbing on ocular surface
      tissue. METHODS: Rabbits (3-4 kg; n = 24) were killed at 0, 4-h, 8-h, and 12-h
      intervals after a 5-min period of eye rubbing. Ocular surface tissues were
      studied by light and scanning electron microscopy. Contralateral eyes served as
      controls. Eye rubbing was accomplished by using digital pressure over the closed
      eyelid with a force sufficient to appreciate by palpation the orbital rim.
      Biomicroscopic examination revealed marked vascular injection of the conjunctiva.
      Ocular surface tissues studied included the lid margins, the upper and lower
      tarsal conjunctivae, the bulbar conjunctiva, and the cornea. RESULTS: Changes in
      the ocular surface included dramatic alteration in the upper tarsal conjunctiva
      when compared with controls. The cornea and bulbar and lower tarsal conjunctiva
      were not altered when compared with control tissues, except for some increase in
      exfoliating cells in the cornea. The surface epithelial cells of the upper tarsal
      conjunctiva had a spheroidal structure and were markedly elevated, the
      microprojections were altered, and there was evidence of increased cellular
      exfoliation. These changes were most pronounced at the 0 and 4-h time points,
      less noticeable at 8 h, and no appreciable changes were observed when compared
      with control tissues at 12 h. CONCLUSION: This study demonstrates that eye
      rubbing causes surface alterations in the stratified cuboidal to columnar
      epithelial surface of the upper tarsal conjunctiva while sparing the stratified
      squamous epithelial surface of the distal lid margins and cornea.

PMID- 9143808
TI  - A comparative study of human corneal keratocyte and endothelial cell density
      during aging.
AB  - PURPOSE: To investigate whether the human corneal keratocyte density changes
      during aging. METHODS: Comparative data on keratocyte and endothelial cell
      density (ECD) were obtained from 178 normal corneas (89 persons ranging in age
      from 30 weeks of gestation to 90 years). Keratocyte density was quantified by
      using biochemical measurements of the stromal DNA/ mass content within the
      central 7-mm diameter zone (sDNA) (1 U equals 1 microgram DNA per milligram of
      dry tissue weight), whereas central ECD was assessed after alizarin red staining.
      RESULTS: In the first decade of life, there was a mean sDNA of 1.64 +/- 0.29 U,
      corresponding to 6.22 +/- 1.1 x 10(4) keratocytes per mm3. A direct correlation
      between keratocyte density and donor age was found (r = -0.49; p < 0.0001) with a
      physiologic decline of 0.3% per year throughout life (density = 6.30 x 10(4)
      keratocytes per mm3-190 x age). A similar decrease of 0.3% per year was observed
      in the ECD during adulthood, whereas the annual decline was 2.9% during infancy
      and childhood. The interindividual variation in keratocyte density was of the
      same magnitude as that seen in ECD. Moreover, keratocyte density was positively
      correlated with ECD (r = 0.23; p < 0.001); however, after correcting for age by
      multiple regression analysis, this correlation disappeared, indicating that
      keratocytes and endothelial cells form distinct cell populations. CONCLUSIONS:
      The study demonstrates a linear loss of human corneal keratocytes as a function
      of age, a loss that parallels the well established decline in ECD.

PMID- 9143809
TI  - Soluble interleukin-2 receptors and serum autoantibodies in dry eye patients:
      correlation with lacrimal gland function.
AB  - PURPOSE: Sjogren's syndrome (SS) is a systemic autoimmune disease characterized
      by decreased lacrimal and salivary gland function causing dry eye and dry mouth.
      We examined several parameters as measures of lacrimal function and compared the
      serum soluble interleukin-2 receptor (sIL-2R) and serum autoantibodies as
      measures of systemic autoimmune condition. METHODS: Serum levels of sIL-2R,
      antinuclear antibody (ANA), and rheumatoid factor (RF) in 128 patients (16 men,
      112 women; average age, 54.3 +/- 12.5 years) were measured. The lacrimal function
      was evaluated clinically. RESULTS. There was no correlation between systemic
      condition and the cotton-thread test, Schirmer test with or without anesthesia,
      tear-clearance test, tear-function index, or the BUT. However, the Schirmer test
      with nasal stimulation and rose bengal and fluorescein staining was positively
      correlated with systemic parameters. CONCLUSION: We show the correlation of serum
      sIL-2R, ANA, and RF to lacrimal function, which is good evidence that systemic
      immune conditions directly affect local lacrimal gland function.

PMID- 9143810
TI  - Abnormalities of the extracellular matrix in keratoconus corneas.
AB  - PURPOSE: To study alterations of the extracellular matrix (ECM) and basement
      membrane (BM) components in human keratoconus corneas. METHODS: Fifteen normal
      and 13 keratoconus corneas were characterized by immunofluorescence with
      antibodies to 23 ECM and BM components. RESULTS: Keratoconus staining patterns
      for posterior nonscarred regions and Descemet's membrane were normal. We focused
      on three areas of keratoconus corneas: (a) nonscarred anterior corneal regions,
      (b) scarred anterior and posterior corneal regions, and (c) gaps in Bowman's
      layer. In each of these areas, consistent ECM and BM changes could be found.
      Nonscarred regions showed decreased staining of the epithelial BM for
      entactin/nidogen, fibronectin, alpha 3-alpha 5 chains of type IV collagen, and
      chains of laminin-1. In contrast, scarred regions had greater than normal
      staining of the epithelial BM for these same components and also for laminin-5,
      perlecan, and type VII collagen. In the Bowman's layer gaps/breaks, focal
      fibrotic deposits containing type VIII collagen, fibrillin-1, tenascin-C, alpha 1
      alpha 2 type IV collagen, and normal stromal ECM and epithelial BM components
      were seen. Fibrotic regions were largely restricted to areas where, because of
      the lack of Bowman's layer, the epithelium was in contact with the stroma.
      CONCLUSIONS: In a single keratoconus cornea, abnormalities in the ECM/BM patterns
      were not uniform. This may reflect locally increased protease activity (where few
      if any BM components are found) and ongoing wound healing (where more BM or ECM
      components or both are found).

PMID- 9143811
TI  - Histologic evaluation during healing of hydrogel core-and-skirt keratoprostheses
      in the rabbit eye.
AB  - PURPOSE: We developed two models that are modifications of our original poly(2
      hydroxyethyl methacrylate) (PHEMA) core-and-skirt keratoprosthesis. In these
      keratoprostheses, the mechanical strength of the skirt has been considerably
      increased with divinyl glycol (DVG) as a cross-linking agent during
      polymerization. In one (KPro I), methyl methacrylate (MMA) was added as comonomer
      to increase cell adhesion, and in the other (KPro II), HEMA was polymerized with
      DVG without comonomer. The aim of this study was to evaluate the process of
      healing and biocolonization and to ascertain whether KPro I demonstrates better
      ingrowth than the mechanically stronger KPro II, after implantation in rabbit
      eyes. METHODS: Ten rabbits were used for each model and studied at five
      predetermined end points up to 26 weeks. The device was implanted as a full
      thickness keratoprosthesis covered with a conjunctival flap. RESULTS: Neither
      prosthesis demonstrated extrusion or retroprosthetic membrane formation. There
      was no significant difference between the two types of prosthesis with respect to
      tissue ingrowth and surrounding tissue melting. Histologically, inflammation was
      not severe, but calcification was seen in most specimens. Evidence of
      biodegradation of the prosthesis also was seen. CONCLUSION: In our original
      keratoprosthesis, fibrovascular invasion had occurred into the prosthetic skirt,
      but wound dehiscence and low mechanical strength resulted in an unfavorable
      outcome. In this series, the mechanical properties were improved, and KPro II was
      stronger than KPro I. Therefore KPro II would be the preferred polymer
      combination for surgical manipulation. However, biodegradation and calcification
      require further investigation into the degree and significance of these adverse
      reactions.

PMID- 9143812
TI  - Herpes simplex blepharoconjunctivitis presenting as complete acquired
      ankyloblepharon.
AB  - PURPOSE: A 90-year-old woman was referred to us with a 1-month history of
      progressively worsening blepharoconjunctivitis. She had a complete acquired
      ankyloblepharon of the right lids, which resulted in the appearance of a right
      upper lid abscess on computed tomography. METHODS: Blepharotomy with separation
      and debridement of the lid margins was performed. RESULTS: Cultures were positive
      only for herpes simplex virus, type II. CONCLUSIONS: Herpes simplex
      blepharoconjunctivitis may take many clinical forms. Our patient's severe
      manifestations led to the clinical and radiologic appearance of preseptal
      cellulitis with a right upper lid abscess.

PMID- 9143813
TI  - Colletotrichum graminicola: a new corneal pathogen.
AB  - PURPOSE: We report the first case of an ocular infection with the fungus
      Colletotrichum graminicola causing keratitis in a 27-year-old man. METHODS:
      Twenty-four months after a postoperative course complicated by recurrent fungal
      keratitis requiring two penetrating keratoplasties, two anterior chamber
      washouts, a conjunctival flap, and medical treatment with topical natamycin,
      intracameral amphotericin B, and oral fluconazole. RESULTS: The patient has shown
      no signs of fungal recurrence despite a failed corneal graft. CONCLUSIONS: C.
      graminicola is a new corneal pathogen and should be included in the differential
      diagnosis of mycotic keratitis.

PMID- 9143814
TI  - The surgical management of an advanced pterygium involving the entire cornea.
AB  - PURPOSE: Conjunctival autografting is a well-established surgical procedure to
      prevent recurrence after pterygium excision. We described a modified technique of
      harvesting an annular autograft to cover a large conjunctival defect after
      excision of an extensive primary pterygium that involved three quadrants of the
      limbus. METHODS: A 73-year-old Chinese farmer underwent an excision of an
      advanced right pterygium involving the entire cornea. A free donor graft was then
      harvested from the remaining superior bulbar conjunctiva to cover the
      conjunctival defect, which involved approximately-three quadrants of limbus. The
      undersized graft was split down the center to create an annular graft to cover
      the defect. RESULTS: Postoperatively, there has been no recurrence over a total
      follow-up period of 11 months. Six months after the initial pterygium surgery, he
      underwent a successful penetrating keratoplasty for residual deep stromal
      scarring. Visual acuity 5 months after the penetrating keratoplasty remained
      stable at 6/18. CONCLUSIONS: This case report shows that a modified technique of
      conjunctival autografting can be successful in preventing recurrence in an
      advanced pterygium after excision. Successful visual rehabilitation with a
      penetrating keratoplasty also was demonstrated in this patient.

PMID- 9143815
TI  - X-ray diffraction and transmission electron microscopy of Morquio syndrome type A
      cornea: a structural analysis.
AB  - PURPOSE: This case report describes the structural characterization of the
      corneal stroma from a patient with Morquio syndrome type A. METHODS: A left
      penetrating keratoplasty was performed, and the cornea was examined using
      transmission electron microscopy and synchrotron x-ray diffraction. The
      interfibrillar proteoglycans were visualized in the electron microscope by using
      cuprolinic blue. RESULTS: Stromal collagen fibrils showed a bimodal distribution
      of diameters: 70% had a distribution comparable to that in normal tissue (20-30
      nm) and 30% contained larger fibrils (30-42 nm) as seen by electron microscopy.
      Both electron microscopy and x-ray diffraction showed that the bulk numeric
      density of fibrils per unit area in cross-section (number density) was higher
      than normal in the Morquio syndrome cornea. The arrangement of proteoglycans
      throughout most of the Morquio syndrome cornea appeared normal, but many of the
      filaments were twice their normal length. In the anterior stroma, very large
      proteoglycan filaments (< or = 400 nm long) were found. Other ultrastructural
      differences also were noted, including abnormal keratocytes and long spacing
      collagen. CONCLUSION: The variation in fibril diameter and number density were
      modeled to account for only a 5% decrease in light scattering compared with the
      normal cornea. The extensive corneal clouding seen in the Morquio syndrome cornea
      cannot therefore be attributed to the variation in fibril diameters; collagen
      free areas and expanded cells seem to be the most likely cause.

PMID- 9143816
TI  - Silicone punctal plug migration resulting in dacryocystitis and canaliculitis.
AB  - PURPOSE: One of the modalities of treating dry eyes is punctal plugs. They are
      usually used for temporary occlusion of the lacrimal drainage system. Among the
      complications associated with silicone punctal plugs are extrusion, downward
      migration, irritation, and epiphora. To our knowledge, this is the first report
      of dacryocystitis and canaliculitis as a result of spontaneous migration of
      punctal plugs into the lacrimal drainage system. METHODS: We describe the
      sequelae of spontaneous migration of silicone punctal plugs into the lacrimal
      drainage system in two patients with dry eyes. RESULTS: In two patients,
      spontaneous migration of silicone punctal plugs into the canaliculus or the
      lacrimal sac, respectively, resulted in canaliculitis or dacryocystitis.
      CONCLUSION: Smaller sized newer generation punctal plugs were designed to
      facilitate insertion; however, this design also increases the likelihood of
      proximal migration within the lacrimal drainage system. The importance of
      monitoring patients after punctal-plug placement cannot be over-emphasized.

PMID- 9143817
TI  - Biochemical tests in diseases of the intestinal tract: their contributions to
      diagnosis, management, and understanding the pathophysiology of specific disease
      states.
AB  - Biochemical testing plays a major role in the complete evaluation of patients
      with suspected or established intestinal disease. We have classified these tests
      according to the medium in which they are performed: breath tests, including
      isotopic and nonisotopic tests, fecal tests, urine tests, serum tests, tissue
      tests, and other tests. The principles of various tests are outlined, and the
      role of each test in the evaluation of particular gastrointestinal disorders is
      discussed.

PMID- 9143818
TI  - Selenium in health and disease: a review.
AB  - Selenium (Se) was discovered 180 years ago. The toxicological properties of Se in
      livestock were recognized first; its essential nutritional role for animals was
      discovered in the 1950s and for humans in 1973. Only one reductive metabolic
      pathway of Se is well characterized in biological systems, although several
      naturally occurring inorganic and organic forms of the element exist. The amount
      of Se available for assimilation by the tissues is dependent on the form and
      concentration of the element. Se is incorporated into a number of functionally
      active selenoproteins, including the enzyme glutathione peroxidase, which acts as
      a cellular protector against free radical oxidative damage and type 1
      iodothyronine 5'-deiodinase which interacts with iodine to prevent abnormal
      hormone metabolism. Se deficiency has been linked with numerous diseases,
      including endemic cardiomyopathy in Se-deficient regions of China; cancer,
      muscular dystrophy, malaria, and cardiovascular disease have also been
      implicated, but evidence for the association is often tenuous. Information on Se
      levels in foods and dietary intake is limited, and an average requirement for Se
      in the U.K. has no been established. Available data suggest that intake in the
      U.K. is adequate for all, except for a few risk groups such as patients on total
      parenteral nutrition or restrictive diets.

PMID- 9143819
TI  - Food control systems in Canada.
AB  - This paper provides an overview of the responsibilities and jurisdictional
      boundaries of Health Canada (HC) and Agriculture and Agri-Food Canada (AAFC) with
      regard to food regulation in Canada. It examines their interagency coordination
      within the federal structure and with other levels of government, industry, and
      the consumer. The international developments are considered with the North
      American Free Trade Agreement (NAFTA) and the Canada, United States Trade
      Agreement (CUSTA) being regarded as likely to have a significant future impact.
      The federal food safety and quality system is complex and fragmented. Federal
      food regulation comes under the jurisdiction of four federal departments: HC,
      AAFC, Industry Canada (IC), and Fisheries and Oceans Canada (FOC). All four
      departments are involved with inspection, surveillance, and the analysis of food
      sold in Canada. In addition, Canada's ten provincial and two territorial
      governments have provincial-, regional-, municipal-, and local-level governments
      that also have jurisdiction over food safety and quality. Consideration is first
      given to the main legislative provision covering food--the Federal Food and Drugs
      Act. This Act is administered by several of the Federal Government departments.
      The role of these departments is examined individually along with additional,
      more specific legal provisions for which responsibility is not divided (in
      particular, the Canada Agricultural Products [CAP] Act administered by AAFC, and
      the Consumer Packaging and Labeling Act [CPLA] administered by IC). The various
      reviews that have taken place in the recent past and those still in progress are
      considered, and the final part of this paper looks at the international
      developments that are likely to have a major impact on the future development of
      the Canadian food control system.

PMID- 9143820
TI  - Heat transfer and lethality considerations in aseptic processing of
      liquid/particle mixtures: a review.
AB  - Consumer awareness and demand for nutritious yet inexpensive food products call
      for innovative processing techniques that have both safety and quality as primary
      objectives. These challenges appear to have been met by aseptic processing
      techniques, especially for liquid and high-acid foods. However, the extension of
      aseptic processing principles to low-acid foods containing discrete particles in
      viscous sauces has not been approved by regulatory agencies, particularly in
      North America. This apparent limitation is due primarily to the lack of adequate
      temperature monitoring devices to keep track of particles in dynamic motion, as
      well as to the residence time distribution of particles flowing in the continuous
      heat-hold-cool sections of the aseptic processing system. These problems have
      prompted active research to describe the phenomenal behavior of particulates
      through sound mathematical modeling and computer simulators. The accuracy of
      mathematical models depends heavily on how accurate input parametric values are.
      These parameters include the thermophysical properties of the carrier fluid and
      particles, as well as the aseptic processing system characteristics in relation
      to residence time distribution and the fluid-to-particle interfacial heat
      transfer coefficient. Apparently, several contradictory findings have been
      reported in the literature with respect to the effect of various processing
      parameters on the above-mentioned input parametric values. The need therefore
      arises for more collaborative studies involving the industry and academia. This
      review brings to perspective, the current status on the aseptic processing of
      particulate foods with respect to the critical processing parameters which affect
      the fluid-to-particle convective heat transfer coefficient associated with
      particulate laden products.

PMID- 9143821
TI  - Preservation of biological materials under desiccation.
AB  - A number of life forms, including seeds, certain nematodes, bacterial and fungal
      spores, and cysts of certain crustaceans, show an ability to survive desiccation.
      The present article reviews the literature available on this subject and
      critically evaluates the evidence for various mechanisms that may be responsible
      for these phenomena. Specific mechanisms considered include vitrification (glass
      formation) by sugars and other polyhydroxy compounds that are accumulated by the
      desiccated structures, specific effects of polyhydroxy compounds on membranes,
      effect of "compatible solutes" on conformation of key proteins, as well as other
      biochemical mechanisms. The article presents potential applications relevant to
      food technology and to biotechnology and reviews the research required to
      materialize more effective use of desiccation in food and biopreservation.

PMID- 9143822
TI  - The uniform approach to breast fine-needle aspiration biopsy. National Cancer
      Institute Fine-Needle Aspiration of Breast Workshop Subcommittees.

PMID- 9143823
TI  - Use of fine-needle aspiration biopsy in the evaluation of splenic lesions in a
      cancer center.
AB  - Fine-needle aspiration biopsy (FNAB) of the spleen was performed on 50 patients,
      of whom 40 had had a previous diagnosis of malignancy (23 lymphoproliferative
      disorders, 13 carcinomas, 3 melanomas, and 1 sarcoma). The cytologic diagnoses
      included 22 cases positive for malignancy (10 lymphomas, 9 metastatic carcinomas,
      2 metastatic melanomas, and 1 sarcoma), 18 cases negative for malignancy, 4 cases
      suspicious for malignancy, and 6 nondiagnostic specimens. No major complications
      were associated with the FNAB procedure, however, one patient did develop a
      pneumothorax that resolved spontaneously. Subsequent splenectomy was performed in
      10 of the 50 cases. There were no false-positive diagnoses, and only one false
      negative diagnosis, which was attributed to sampling error. The aspirate, showing
      only benign splenic parenchyma, was from a patient with splenomegaly and no
      previous diagnosis; subsequent splenectomy showed acute myelogenous leukemia. In
      our study, FNAB proved to be a safe and valuable diagnostic tool for evaluating
      splenic lesions in oncologic patients.

PMID- 9143824
TI  - Cytologic findings in tenosynovial giant cell tumors investigated by fine-needle
      aspiration cytology.
AB  - Tenosynovial giant cell tumor is a relatively common benign proliferation
      affecting the articular and periarticular soft tissues. Cytologic findings on
      smears obtained by fine-needle aspiration are rather characteristic and include a
      mixture of oval or polygonal mononuclear cells showing vacuolation and/or pigment
      deposition along with a population of multinucleated giant cells. Separation from
      other giant cell lesions including true giant cell tumor of bone,
      chondroblastoma, aneurysmal bone cyst, and granulomatous inflammation must be
      made. Careful attention to the cytologic findings and correlation with clinical
      and radiographic data should result in the appropriate diagnosis of tenosynovial
      giant cell tumor in most cases.

PMID- 9143825
TI  - Role of fine-needle aspiration cytology in the preoperative evaluation of smooth
      muscle tumors.
AB  - A preliminary study was undertaken to assess the feasibility and the diagnostic
      role of fine-needle aspiration cytology (FNAC) in the preoperative evaluation of
      eight uterine smooth muscle tumors manifesting as single large masses with signs
      of growth. Percutaneous FNAC was performed under echographic control with a 22
      gauge needle and the material was stained according to conventional techniques.
      Histology of surgically resected specimens was available for final diagnosis and
      comparative analysis in all the cases, including five leiomyomas (LM), one smooth
      muscle tumor of uncertain malignant potential (TUMP), and two low-grade
      leiomyosarcomas (LMS). Cellularity, as indicated by the density (crowding) of
      nuclei reflecting the amount of cytoplasmic volume, and the cohesiveness of the
      tissue fragments in the smears appeared to be the most important diagnostic
      parameters in the distinction between LM and LMS. LM usually showed few scattered
      poorly cellular fragments of highly cohesive tapering cells without nuclear
      crowding and with abundant cytoplasm. LMS usually showed a large number of single
      cells and fragments of loosely arranged tapering cells with nuclear enlargement
      and crowding and ill-defined scanty cytoplasm. Borderline forms such as TUMP were
      hardly distinguishable from LMS and LM. FNAC appears to be a feasible
      preoperative procedure in uterine smooth muscle tumors and may play a diagnostic
      role, especially in distinguishing frankly benign from overtly malignant forms.

PMID- 9143826
TI  - Modified interphase cytogenetics technique as an adjunct in the analysis of
      atypical cells in body fluids.
AB  - Our objective was to determine the value of a modified interphase cytogenetics
      technique (MICT) by fluorescence in situ hybridization (FISH) in the study of
      atypical cells in body fluids in previously stained slides, allowing a direct
      morphologic-cytogenetic correlation. Thirty-five cases (29 bladder washes, four
      pleural fluids, two ascitic fluids) initially diagnosed as "atypical" with
      subsequent histologic confirmation were included. Histologically, there were 25
      malignant four dysplastic, and six benign lesions. Previously Papanicolaou or
      Diff-Quick-stained slides were marked to determine the location of the cells of
      interest prior to FISH analysis. A pretreatment modification using pepsin
      digestion was utilized. Chromosome-specific probe 8 (Vysis) was used to detect
      numerical chromosomal abnormalities (NCA) involving chromosome 8. Various NCA
      (aneuploid) were detected in the atypical cells of histologically proven
      malignant cases but not in the benign cases. Using histology as a "gold
      standard," FISH has a sensitivity of 83% and a specificity of 100%. In conclusion
      this study shows that a MICT by FISH on previously stained slides can serve as an
      adjunct in the study of atypical cells in body fluids. This technique allows a
      direct morphologic-cytogenetic correlation which in the future may aid in the
      better understanding of carcinogenesis.

PMID- 9143827
TI  - Fine-needle aspiration cytology of pleuropulmonary blastoma: case report and
      review of the literature.
AB  - This report describes the fine-needle aspiration (FNA) cytology of a case of
      pleuropulmonary blastoma in a 3-yr-9-mo-old male. Pleuropulmonary blastoma is
      considered by most authors to be distinct from pulmonary blastoma and is a rare
      malignant tumor of the intrathoracic cavity. FNA smears were cellular with
      numerous small ovoid to spindled cells with oval to elliptical nuclei exhibiting
      finely granular chromatin and inconspicuous nucleoli. The cytoplasm was scant and
      eosinophilic with indistinct borders. Focal chondroid material and blastema-like
      cells were noted. The differential diagnosis suggested by the cytologic findings
      included rhabdomysosarcoma, teratoma, neuroblastoma, malignant mesenchymoma,
      pleuropulmonary blastoma, and metastatic tumor. To our knowledge, this is the
      first report of the cytology of this tumor.

PMID- 9143828
TI  - Cytologic features of pulmonary metastasis from a granulosa cell tumor diagnosed
      by fine-needle aspiration: a case report.
AB  - We report on a case of a granulosa cell tumor of the ovary metastatic to the lung
      and diagnosed by fine-needle aspiration. The patient was a 70-yr-old woman who
      was diagnosed with a granulosa cell tumor of the ovary 17 yr previously. She
      subsequently developed abdominal metastases and received several cycles of
      chemotherapy. A 0.5-cm right upper lobe pulmonary nodule was found on a routine
      chest radiograph and subsequent computerized tomography scan. Aspiration cytology
      of this pulmonary nodule demonstrated small, relatively uniform neoplastic cells
      with nuclear grooves and indentations consistent with a granulosa cell tumor. The
      differential diagnosis of granulosa cell tumors from other metastatic and
      pulmonary lesions is reviewed.

PMID- 9143829
TI  - Low-grade lymphoma of mucosa-associated tissue in the parotid gland: a case
      report of fine-needle aspiration cytology diagnosis using flow cytometric
      immunophenotyping.
AB  - A 66-year-old woman with Sjogren's syndrome for 7 years presented with an
      enlarged right parotid gland. The left parotid gland, which showed myoepithelial
      sialadenitis (MESA), had been resected 4 years earlier. A fine-needle aspiration
      (FNA) biopsy of the right parotid gland was performed. Examination of the smears
      revealed cells of intermediate size with a round-to-irregular nuclear outline and
      distinct pale cytoplasm intermixed with small mature round lymphocytes. The
      chromatin was slightly paler and less clumped than in small mature lymphocytes. A
      small inconspicuous nucleolus was seen in most of the cells. Flow cytometry
      immunophenotyping performed on the FNA biopsy material showed a monoclonal
      population of B cells with kappa light chain restriction. The cytomorphology
      coupled with the immunophenotyping study in this clinical context suggested the
      diagnosis of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue
      (MALT). Extensive staging work-up revealed no evidence of disseminated disease.
      The right parotid gland was surgically excised. Histology and gene rearrangement
      studies confirmed the cytologic diagnosis. To our knowledge, this is the first
      description of a low-grade lymphoma of MALT in a salivary gland to be diagnosed
      by FNA.

PMID- 9143830
TI  - Bronchioloalveolar lavage in the diagnosis of CMV pneumonitis in lung transplant
      recipients: an immunocytochemical study.
AB  - Cytomegalovirus (CMV) pneumonitis is a common opportunistic infection in lung
      transplant recipients. Its diagnosis usually rests on the identification of viral
      inclusions in lung parenchyma obtained by transbronchial biopsy, or by
      examination of the cytologic material obtained by bronchioloalveolar lavage
      (BAL). To determine whether the use of immunocytochemistry (ICC) increases the
      sensitivity of cytology in the diagnosis of CMV pneumonitis, we retrospectively
      selected 17 cases in which transbronchial biopsy and BAL were performed
      simultaneously, and had positive histology with negative cytology. Five negative
      controls were selected. The 22 slides were decolorized and restained with ICC for
      CMV. Of the 17 slides, nine (53%) showed cells with positive nuclear staining.
      All controls were negative. These results were then correlated with the number of
      infected cells present in the biopsy tissue, and the location of the cells
      (interstitial vs. intraalveolar). A good correlation was found between positive
      cytology and intraalveolar location of infected cells, and no correlation was
      seen between number of infected cells in the biopsy and the positive cytology. In
      summary, although histologic evaluation of lung parenchyma obtained by
      transbronchial biopsy is more sensitive for diagnosis of CMV pneumonitis, the
      sensitivity of the cytologic evaluation of BAL material can be increased by the
      use of ICC. The likelihood of positive ICC seems to be related to the presence of
      infected cells in the alveolar space rather than to the number of infected cells.

PMID- 9143831
TI  - Pulmonary sequestration--a diagnostic pitfall: a case report.
AB  - Pulmonary sequestration is defined as a congenital malformation of abnormal lung
      tissue that does not communicate with the airway system and that receives blood
      supply from anomalous arteries. The majority of these sequestrations are
      encountered in the pediatric population. Surgical excision is the treatment of
      choice, with excellent prognosis. We studied a case of an extralobar pulmonary
      sequestration in a young adult, presenting as an intrathoracic mass; it was
      aspirated twice, final diagnosis being rendered after surgical resection. The
      cytologic findings and the accompanying diagnostic difficulties to our knowledge
      have never been reported.

PMID- 9143832
TI  - Bile duct brushings cytology: potential pitfalls in diagnosis.
AB  - Bile duct brushings (BDB) are the method of choice for pathological diagnosis of
      malignancy of the hepatobiliary system in our institution. We examined results of
      the cytological assessment of 267 BDB and compared them with biopsies, which were
      available in 131 cases. Sensitivity of BDB for diagnosis of malignancy was 44%
      and specificity 100%, in keeping with the experience of others. The review of
      "false-negative cases" reveals four main reasons for the relatively modest
      sensitivity of BDB in diagnosis of malignancy: poor sampling, lack of diagnostic
      criteria for dysplasia-carcinoma in situ, difficulties in recognition of special
      tumor types, and underestimating the significance of the smear background. After
      a critical review and with regard to these issues, the sensitivity of BDB in our
      series could have been improved to 78%. We conclude that BDB can give a confident
      and definitive diagnosis of malignancy, which can be relied upon without a tissue
      biopsy. A negative result does not exclude malignancy.

PMID- 9143833
TI  - Guidelines for seeking and offering consultations in cytopathology.

PMID- 9143834
TI  - Comparison of ThinPrep and conventional preparations: nongynecologic cytology
      evaluation.
AB  - ThinPrep processing, an automated cytopreparatory method, has been reported to
      show good correlation with conventional preparations and to reduce the rate of
      false-negative diagnoses. In a retrospective review of 230 consecutive
      nongynecologic cytology cases, we compare the ThinPrep (TP) method with
      conventional preparations (CP). There were 129 fine-needle aspiration (FNA)
      specimens from various sites, including 51 breasts, 40 thyroids, 14 lungs, 8
      livers, and 16 miscellaneous sites. The sources of 101 body cavity fluids
      included 68 pleural/peritoneal effusions, 25 peritoneal/pelvic washings, and 8
      miscellaneous sites. Each case was evaluated for cellularity, morphologic,
      details, and obscuring background material. Diagnoses of the TP slides were
      classified as insufficient, normal, benign, suspicious, or malignant. Each case
      was then correlated with the tissue diagnosis when available. In TP slides,
      cellular arrangements, nuclear details, and nuclear cytoplasmic ratio were
      preserved, while blood and diathesis were eliminated. There was no statistically
      significant difference between TP and CP in the diagnostic categories. However,
      in six cases of "insufficient for diagnosis" on FNA by CP, TP yielded sufficient
      cells and tissue fragments for diagnosis. One case each of FNA and body fluid
      with a diagnosis of "suspicious for malignancy" by CP was considered "positive"
      on TP slides. The overall sensitivity of TP was 97.6%, and the specificity was
      92.9%. The positive predictive value was 93.0%. We conclude that the ThinPrep
      method shows good correlation with conventional preparations in both FNA and body
      fluids.

PMID- 9143835
TI  - Epithelioid hemangioendothelioma in pleural fluid.

PMID- 9143836
TI  - Detection of aneuploidy in mesothelioma cell lines by fluorescence in situ
      hybridization (FISH)

PMID- 9143837
TI  - Guidelines and standards: help or hindrance?

PMID- 9143838
TI  - Histocytologic diagnosis of neuroendocrine tumors in the liver: a retrospective
      study of 23 cases.
AB  - A series of 23 needle biopsies of neuroendocrine tumors occurring in the liver is
      described. Aspirate smears, core biopsies, and touch preparations were examined.
      Eighteen of the 23 patients had been previously diagnosed: 9 patients had been
      correctly identified as having a neuroendocrine tumor, and 9 patients had been
      originally misdiagnosed. Five of the patients in this series had no previously
      identified neoplasia. Immunohistochemical staining confirmed the neuroendocrine
      nature of the tumors in each of the cases. On the basis of cytomorphology, these
      cases were subtyped as either round cell type, spindle cell type, or polygonal
      cell type. The polygonal cell type of neuroendocrine tumor, as well as rare
      examples of the round cell type, demonstrated features similar to well
      differentiated hepatocellular carcinoma and adenocarcinomas, and may present a
      diagnostic dilemma. Characteristic cytologic attributes of the polygonal cell
      type of neuroendocrine tumor which aid in its distinction from well
      differentiated hepatocellular carcinoma include eccentrically located
      "plasmacytoid" nuclei and cellular discohesion. Findings on core needle biopsy
      which further identify the neuroendocrine tumors are thick fibrous stroma or
      small "nests" of tumor cells. The additional use of immunohistochemical staining
      provides reliable evidence of the cell of origin in confusing cases. Attention to
      these considerations will aid in the cytologic diagnosis of neuroendocrine
      tumors.

PMID- 9143839
TI  - Posttransplant lymphoproliferative disorders: a fine-needle aspiration biopsy
      study.
AB  - Fine-needle aspiration biopsy (FNAB) has been used with high sensitivity and
      specificity in the diagnosis of both Hodgkin's and non-Hodgkin's lymphoma.
      However, studies of FNAB of posttransplant lymphoproliferative disorders (PTLDs)
      are rare. The clinical course of 593 allograft recipients (cardiac, 288; renal,
      250; lung, 50; and heart/lung, 5) was reviewed. Twenty-six patients developed
      PTLD with an overall incidence of 4.4%. Of these patients, 12 underwent FNAB.
      Their age ranged from 33-67 yr (mean, 55 yr). The interval between
      transplantation and FNAB ranged between 2-14 mo (average, 8.4 mo). The lungs were
      the most common site aspirated (7 cases), followed by lymph nodes (3 cases) and
      other extranodal sites (2 cases, liver and paraspinal mass). The cytologic
      features of these aspirates could be classified into two categories: a
      polymorphous smear composed of a spectrum of mature and immature lymphocytes with
      scattered plasma cells and histiocytes; and a monotonous population of large
      lymphoid cells consistent with malignant lymphoma, large-cell type. Surgical
      biopsies were available in 10 (83.3%) cases and confirmed the FNAB diagnosis. In
      summary, FNAB appears to be a highly sensitive and specific diagnostic tool in
      patients with PTLD.

PMID- 9143840
TI  - Distinction between bronchioloalveolar carcinoma and hyperplastic pulmonary
      proliferations: a cytologic and morphometric analysis.
AB  - The objectives of this study were to identify key cytologic features for the
      morphologic differentiation of bronchioloalveolar carcinoma from reactive
      pulmonary proliferations, and to determine if morphometry of the cytologic
      specimens could provide additional data to distinguish the two processes. We
      analyzed 15 morphologic criteria in pulmonary cytologic specimens from 17
      histologically proven cases of bronchioloalveolar carcinoma and 13 cases with
      reactive cellular changes and compared the findings using univariate analysis.
      This revealed four statistically significant features more commonly associated
      with bronchioloalveolar carcinoma: (i) predominance of two- and three-dimensional
      tissue fragments, (ii) tenacious intercytoplasmic connections between cells,
      (iii) intranuclear cytoplasmic inclusions, and (iv) paucity of multinucleated
      cellular forms. Morphometric measurement revealed significant differences between
      the mean of the nuclear area of benign reactive cells and that of the malignant
      cells. The utilization of these criteria is helpful to diagnose
      bronchioloalveolar carcinoma and to distinguish it from reactive pulmonary
      processes.

PMID- 9143841
TI  - Cytologic diagnosis of acinic-cell carcinoma of salivary glands.
AB  - The cytologic findings in fine-needle aspiration (FNA) biopsies obtained from 40
      primary and 18 recurrent acinic-cell carcinomas (ACC) were retrospectively
      analyzed. Cytomorphologically, ACC is characterized by acinar differentiated
      tumor cells. In addition to these diagnostic clue cells, other types of
      neoplastic cells including vacuolated cells, cells resembling oncocytes, and
      nonspecific glandular cells are encountered. A pronounced lymphocytic reaction is
      a hallmark in 10% of ACC aspirates. Both the variety of tumor cell
      differentiation and the pronounced lymphocytic reaction observed in ACC aspirates
      may result in confusion with other salivary gland lesions. The differential
      diagnosis of ACC encompasses adenocarcinoma, mucoepidermoid carcinoma,
      pleomorphic adenoma, Warthin tumor, sebaceous lymphadenoma, benign
      lymphoepithelial lesion, sialoadenosis, sialadenitis caused by radiotherapy, and
      lymphadenitis. Primary ACCs were correctly diagnosed in 68%; additionally, ACC
      was suspected or included in the differential diagnosis in 15%. Increased
      familiarity with the spectrum of cytomorphologic findings and the potential
      diagnostic pitfalls in ACC will improve the cytodiagnosis of this neoplasm.

PMID- 9143842
TI  - Improving the diagnostic accuracy of cytologic cerebrospinal fluid examinations
      in acute lymphoblastic leukemia using high-power microscopy and terminal
      deoxynucleotidyl transferase determinations.
AB  - In patients with acute lymphoblastic leukemia (ALL), cytologic examination of
      cerebrospinal fluid (CSF) is becoming increasingly important for clinical
      management. In order to enhance the diagnostic accuracy of CSF cytology results,
      the value of using terminal deoxynucleotidyl transferase (Tdt) and high-power
      (1,000x) light microscopy, together with conventional cytologic examination was
      assessed. In 33 CSF samples from ten multiply examined Tdt-positive ALL patients,
      original cytologic interpretations were compared to Tdt results. Cytology samples
      were reviewed by two pathologists (one with hematopathologic expertise). The
      cases in which cytologic interpretation did not correlate with Tdt result were
      first reviewed via 1,000x microscopy without knowledge of Tdt result, then re
      reviewed with knowledge of Tdt result. Conventional cytology alone diagnosed 64%
      of cases accurately (Tdt representing the comparative standard). High-power
      microscopy increased the correlation to 82%. Use of high-power microscopy and
      knowledge of Tdt result together produced a total of 85% of cases with
      correlation of results. High-power microscopic examination therefore contributes
      significantly to the accurate diagnosis of ALL, and knowledge of the Tdt result
      at the time of cytologic examination produces an additional advantage in
      providing an objective measure for CSF involvement by leukemia. Using all three
      methods in conjunction is recommended in order to increase the overall accuracy
      of CSF examination for the detection of leukemic involvement in ALL patients.

PMID- 9143843
TI  - In situ hybridization of chromosome 6 on fine-needle aspirates from breast
      carcinomas: comparison of numerical abnormalities and ER/PgR status and staining
      pattern.
AB  - The estrogen receptor (ER) gene is located on chromosome 6. The aim of our study
      was to investigate whether numerical chromosomal aberrations were reflected in
      estrogen/progesterone receptor (PgR) status and staining pattern. Fine-needle
      aspirates from 51 breast carcinomas were investigated immunocytochemically for
      ER/PgR and by in situ hybridization technique using digoxigenin-labeled alpha
      satellite probe for chromosome 6. Cases with > or = 70% two-signal nuclei were
      regarded as disome; the remaining tumors showed aneusomy with a variable number
      of signals. Aneusomy was found in 32 tumors (63%), whereas 19 (37%) had a normal
      number of chromosome 6. Chromosomal gain occurred in all aneusome cases except
      one. ER- and/or PgR-positive tumors had an equal distribution of disomy and
      aneusomy. Variable ER staining pattern or ER and/or PgR negativity was associated
      with numerical aberrations in chromosome 6 in 76% of the tumors. Cancers with
      uniform ER staining pattern all had normal chromosome number.

PMID- 9143844
TI  - Fine-needle aspiration cytology findings in a case of aggressive angiomyxoma: a
      case report and review of the literature.
AB  - Aggressive angiomyxomas are uncommon but distinct soft-tissue neoplasms occurring
      predominantly in the pelvis and peritoneum of females, but they have occasionally
      been reported in association with inguinal hernias in males. Histologically,
      these neoplasms are characterized by a proliferation of spindle- or stellate
      shaped cells widely separated by loose myxoid stroma in which is dispersed a
      prominent vascular component. The vascular component is comprised of large, thick
      walled vessels that generally to not show an arborizing pattern. Mitotic activity
      has been exceedingly low in the cases reported. Because of their occurrence
      within the groin, these lesions may undergo fine-needle aspiration (FNA).
      Cytologic examination of this material will reveal hypocellular smears containing
      scattered spindle cells with bipolar cytoplasmic processes, as well as bland
      stellate cells. The nuclei are fusiform to oval with a bland chromatin pattern.
      The stromal cells lie in a background of watery myxoid material. While specific
      diagnosis by FNA is not possible, the recognition of this cytologic appearance
      should exclude lymphoproliferative processes as well as metastatic disease from
      the differential diagnosis. Careful attention to cytologic detail should also
      help exclude certain other myxoid neoplasms, especially myxoid liposarcoma. Once
      the myxoid stromal nature of the proliferation is recognized, a differential
      diagnosis of myxoid lesions can be considered along with a recommendation for
      open biopsy to establish the definitive diagnosis.

PMID- 9143845
TI  - Microinvasive adenocarcinoma of the cervix: a cytohistopathologic study of 40
      cases.
AB  - Cervical smears obtained from 40 women with a histologic diagnosis of
      microinvasive adenocarcinoma (MIA) were reexamined for features of invasion. In
      our study MIA was defined as stromal invasion by adenocarcinoma cells to 5 mm or
      less beyond a surface epithelium and without lymphovascular involvement. In 24
      cervices, squamous carcinoma in situ was a coincidental histologic finding. All
      40 smears contained atypical glandular cells (AGC) forming pseudosyncytial
      clusters, and 12 showed additional features suggestive of invasion; pleomorphic
      nuclei, coarse irregular chromatin, karyorrhectic nuclei, and cell detritus. The
      invasive features tended to occur together and were found more than twice as
      frequently in this group than in the remaining 28 smears. There was little
      difference between the two groups in the frequency of super-crowded cell
      clusters, acini, cell strips, isolated cells, nuclear hyperchromasia,
      macronucleoli, or normal cervical glandular cells. Fourteen smears from the 24
      cervices with squamous carcinoma in situ contained cells from a high-grade
      squamous intraepithelial lesion. It is concluded that cervical cytologic
      examination has a sensitivity of 30% (12/40) for the identification of stromal
      microinvasion in adenocarcinoma in situ. Cell detritus, present in 5/12 smears,
      is considered highly specific for invasion but lacks sensitivity. Due to the more
      proximal location and ease of sampling, cytologic examination has a sensitivity
      of 58% (14/24) for histologically confirmed coexisting squamous lesions.

PMID- 9143846
TI  - Needle aspiration cytology of low-grade transitional cell carcinoma of the renal
      pelvis.
AB  - Five cases of histologically confirmed grade 1 papillary transitional cell
      carcinoma of the renal pelvis investigated by needle aspiration biopsy cytology
      were reviewed. In all cases the needle aspirates were hypercellular. Abundant
      benign-appearing urothelial cells in thick clusters, in small aggregates, and
      singly were seen in two cases. Numerous single and loosely aggregated urothelial
      cells with cytoplasmic extensions and slightly pleomorphic nuclei were noted in
      one case. In two patients numerous urothelial fragments of variable sizes showing
      defined cytoplasm and mildly nuclear pleomorphism were the main cellular
      findings.

PMID- 9143847
TI  - Adenoid cystic carcinoma of the breast: utility of immunocytochemical study with
      collagen IV on fine-needle aspiration.
AB  - A case of adenoid cystic carcinoma (ACC) of the breast in a 71-year-old woman is
      reported. This neoplasm accounts for about 0.1% of all breast cancers. The
      mammography showed a well-delineated mass without calcifications. Cytologic
      examination of percutaneous fine-needle aspiration (FNA) material gave the
      diagnostic of ACC, which was confirmed by histologic examination. This report
      emphasizes the utility of immunocytochemical study with collagen IV antibody on
      FNA material of this uncommon tumor.

PMID- 9143848
TI  - Cytopathology of renal collecting duct carcinoma in urine sediment.
AB  - Two cases of histologically, immunohistochemically, and ultrastructurally
      confirmed collecting duct carcinoma of the kidney (CDCK) with positive urine
      cytology are reported. The patients' urine sediments showed malignant glandular
      cells in sheets with defined, variable, granular cytoplasm and oval,
      hyperchromatic nuclei containing micro- or macronucleoli. The cytologic
      differential diagnosis of CDCK is briefly discussed.

PMID- 9143849
TI  - Fine-needle aspiration diagnosis of enterogenous cyst of the orbit: a case
      report.
AB  - Enterogenous cyst is a benign lesion derived from misplaced endodermal
      epithelium. We report the aspiration cytology findings of an orbital cyst from a
      32-year-old woman. The smears contain benign-appearing cuboidal glandular cells
      with focal mucinous features. Carcinoembryonic antigen level in the cyst fluid
      was markedly elevated. These findings are consistent with recurrence of the
      enterogenous cyst initially diagnosed 7 years earlier.

PMID- 9143850
TI  - Papillary tissue fragments as a diagnostic pitfall in fine-needle aspirations of
      thyroid nodules.
AB  - Fine-needle aspirates of three thyroid nodules displayed hypercellularity and
      papillary tissue fragments that suggested neoplasms. Neither microfollicles
      (either empty or with inspissated colloid) nor the characteristic nuclei of
      papillary carcinoma were evident. Surgical specimens contained adenomatoid
      nodules with focal papillary hyperplasia. These cases demonstrate that no single
      cytologic feature should be used independently in the cytologic diagnosis of
      thyroid lesions. Tumor cellularity and papillary tissue fragments should not be
      equated with neoplasia per se; all cytomorphologic features should be evaluated.

PMID- 9143851
TI  - Thymic epithelial cells as a diagnostic pitfall in the fine-needle aspiration
      diagnosis of primary mediastinal lymphoma.
AB  - The cytologic diagnosis of primary mediastinal lesions is challenging due to the
      large number of lesions which may arise (i.e., lymphoma, thymoma, germ cell
      tumor), often with overlapping cytomorphologic features. We present an
      instructive case of primary mediastinal non-Hodgkin's large-cell lymphoma with
      sclerosis, entrapping thymic epithelium. Preoperative fine-needle aspiration
      yielded predominantly epithelial fragments and few lymphoid cells leading to the
      cytologic misdiagnosis of thymoma. The entity of primary mediastinal large-cell
      lymphoma (LCL) is discussed and correlated with the cytologic features seen. In
      addition, histologic sections from 15 additional cases of primary mediastinal LCL
      were evaluated to determine the frequency with which significant numbers of
      epithelial fragments may be observed.

PMID- 9143852
TI  - Appearance of "collagen balls" in ascitic fluid cytology with abdominal cocoon
      (encapsulating peritonitis)

PMID- 9143853
TI  - Oral antihyperglycaemics. Considerations in older patients with non-insulin
      dependent diabetes mellitus.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) is increasing in incidence as the
      population in most countries ages. Multiple pathology is common in the elderly,
      and cardiovascular disease is usually present at diagnosis. Patients who develop
      NIDDM at age 65 years may live long enough to develop microvascular
      complications. Others who are frail and have multiple pathologies may require
      treatment to prevent both symptomatic hyperglycaemia and dehydration, whilst
      avoiding hypoglycaemia. The goals in the management of NIDDM in elderly people
      are the prevention of complications and the relief of symptoms. Treatment must be
      tailored to the individual's expectations and should be reviewed regularly with
      the changing circumstances of aging. If dietary measures fail to control glucose
      levels, antihyperglycaemic sulphonylureas are the most frequently prescribed form
      of treatment. However, concern over the potential of these drugs to cause
      hypoglycaemia limits the choice to second generation sulphonylureas, agents that
      preserve the first phase of insulin release and have non-biologically active
      metabolites that are promptly eliminated. The biguanide agent metformin is also
      appropriate in elderly obese patients with NIDDM who do not have renal, liver or
      cardiac failure. The combination of a sulphonylurea and metformin can be
      effective in patients in whom insulin would otherwise be required. Novel
      compounds such as acarbose and the thiazolinediones may also be useful in the
      treatment of older diabetic patients.

PMID- 9143854
TI  - Using liquid levodopa in the treatment of Parkinson's disease. A practical guide.
AB  - Many patients with Parkinson's disease develop both involuntary movements from
      and a critical dependency on, levodopa therapy as their disease progresses. This
      results in a narrow therapeutic window in which blood concentrations of levodopa
      can achieve optimal control of parkinsonian symptoms. The short half-life of
      levodopa, combined with loss of intraneuronal storage capacity for levodopa as
      the disease progresses, results in patients experiencing marked motor
      fluctuations complicated by medication-induced dyskinesias. When given in tablet
      form, the dosage of levodopa (which is usually combined with a decarboxylase
      inhibitor such as carbidopa or benserazide) often cannot be titrated adequately,
      and the drug may become unpredictable in its ability to relieve parkinsonian
      symptoms. A solution of levodopa and carbidopa, stabilised using ascorbic acid,
      offers a means of delivering a titrated amount of levodopa at regular intervals.
      Solutions pass through the stomach faster than solids, affording more rapid
      symptomatic relief in some patients with Parkinson's disease.

PMID- 9143855
TI  - Optimal management of chronic leg ulcers in the elderly.
AB  - Chronic leg ulceration is a very common clinical problem in the elderly. Good
      management depends entirely on making an accurate diagnosis, and planning
      treatment after considering all aspects of patient well-being. All elderly
      patients with leg ulcers benefit from an assessment of their vascular status,
      since the effects of gravity influence treatment and healing irrespective of the
      diagnosis. The most common causes of ulceration are venous and arterial disease.
      Diabetes mellitus, pressure, vasculitis, metabolic abnormalities and skin cancer
      are all unusual causes of leg ulceration, but must be considered in the
      differential diagnosis. Almost all patients with ulcerated legs benefit from the
      use of compression bandaging at a level appropriate to their vascular status. In
      patients with venous ulcers, this can be achieved with a number of bandaging
      techniques; however, multilayer bandaging appears to be the most cost-effective
      means available, particularly when combined with community-based leg ulcer
      clinics. The effects of oral drug therapy for venous and arterial disease have
      been disappointing. Local dressings are important in ulcers that are not suitable
      for compression therapy. The choice of dressing depends on the nature of the
      ulcer and the tolerability of the dressing for the patient.

PMID- 9143856
TI  - Benign prostatic hyperplasia. Practical treatment guidelines.
AB  - Symptomatic benign prostatic hyperplasia (BPH) is a common condition in older men
      and has a significant impact on their daily lives. Transurethral resection of the
      prostate (TURP) or open prostatectomy are currently the most effective therapies
      for BPH. TURP is, however, associated with clinically significant adverse events
      in 20% of patients. Therefore, patients who need treatment for BPH based on the
      presence of symptoms should also be offered other therapy options. Transurethral
      incision of the prostate is an effective therapy with minimal adverse effects in
      patients with a prostate not larger than 30 g. Minimally invasive procedures,
      such as electrovaporisation, laser prostatectomy, transurethral needle ablation,
      high intensity focused ultrasound, transurethral microwave therapy and insertion
      of prostatic stents, can be performed instead of the standard surgical
      procedures. They are either performed as outpatient procedures or are associated
      with shorter durations of hospitalisation than TURP; in addition, they can also
      be performed in high risk patients. The efficacy of these procedures lies between
      that of TURP and medical therapy. Medical therapy is becoming increasingly
      important in the treatment of patients with moderate symptoms of BPH. Both
      androgen-suppressing therapy and alpha-adrenoceptor blockade are well tolerated
      and effective modalities. Compared with placebo, both types of therapy produce
      improvements in maximum urinary flat rate and reductions in symptom scores of 15
      to 20%. Finasteride, a potent 5 alpha-reductase inhibitor, must be given for 6
      months before it effectiveness in a given patient can be assessed, and for at
      least 12 months to achieve maximum prostate shrinkage and the full extent of its
      other beneficial effects. This may be perceived as a disadvantage when compared
      with the rapid relief afforded by surgery or alpha-blockade. The efficacy of
      finasteride is also dependent on prostate size; it should not be tried in
      patients with a prostate volume of < 40 ml. On the other hand, finasteride may
      reverse the progression of the disease process. Of the alpha 1-adrenoceptor
      antagonists, terazosin, doxazosin and tamsulosin can be administered once daily.
      In contrast, prazosin, alfuzosin and indoramin must be administered twice daily,
      which may have a negative impact on patient compliance. Because of its
      specificity for alpha 1A-receptors, no dosage titration is needed when tamsulosin
      is used; in addition, in contrast with the other alpha-blockers used in BPH,
      tamsulosin lacks significant effects on blood pressure. On the other hand,
      nonselective alpha-blockers are preferable in hypertensive patients with BPH. The
      final decision about the best treatment for a particular patient must take into
      account the patient's preference after he has been informed of the different
      options.

PMID- 9143858
TI  - Dorzolamide. A review of its pharmacology and therapeutic potential in the
      management of glaucoma and ocular hypertension.
AB  - Dorzolamide (dorzolamide hydrochloride), the first topical carbonic anhydrase
      (CA) inhibitor to become available for clinical use, lowers intraocular pressure
      (IOP) by reducing aqueous humour formation. It is formulated as a 2% eyedrop for
      use in the management of glaucoma and ocular hypertension. When administered 3
      times daily, dorzolamide is effective in lowering IOP in patients with open-angle
      glaucoma or ocular hypertension. Mean IOP was reduced by approximately 4 to 6 mm
      Hg at peak (2 hours postdose) and 3 to 4.5 mm Hg at trough (8 hours postdose) in
      clinical trails. A 1-year comparative study showed that the ocular hypotensive
      efficacy of dorzolamine 2% 3 times daily was similar to that of betaxolol 0.5%
      twice daily, but slightly inferior to that of timolol 0.5% twice daily.
      Dorzolamide has additive ocular hypotensive effects when used in conjunction with
      topical beta-adrenergic antagonists and was as effective as pilocarpine 2% 4
      times daily as adjunctive therapy in patients receiving timolol. Dorzolamide does
      not appear to produce the acid-base or electrolyte disturbances and severe
      systemic adverse events associated with oral CA inhibitors, and unlike beta
      adrenergic antagonists, it is not contraindicated in patients with asthma,
      reactive airways disease or heart disease. Furthermore, as CA inhibitors do not
      cause miosis, they may cause less interference with vision than pilocarpine or
      epinephrine (adrenaline). The most common adverse effects associated with
      dorzolamide are bitter taste and transient local burning or stinging.
      Conjunctivitis was the most common reason for discontinuation of dorzolamide in
      one large study. Thus, available data suggest that dorzolamide has potential as
      an alternative therapy option in patients with glaucoma or ocular hypertension
      who are intolerant of, or unable to receive, ophthalmic beta-adrenergic
      antagonists and as adjunctive therapy in patients already receiving these agents.
      Further efficacy and tolerability data are needed to determine the place of
      dorzolamide in therapy.

PMID- 9143857
TI  - Neuropsychiatric adverse effects of antiparkinsonian drugs. Characteristics,
      evaluation and treatment.
AB  - Parkinson's disease (PD) is a progressive neurological condition that causes
      considerable disability in the elderly. Drugs used to treat PD, such as levodopa,
      offer symptomatic relief but often have neuropsychiatric adverse effects, most
      prominently psychosis and delirium. Aged patients and those with dementia are
      particularly vulnerable to these adverse effects. Evaluating PD patients with
      drug-induced neuropsychiatric adverse effects is made difficult by their complex
      clinical presentations. The treatment of drug-induced psychosis and delirium
      begins with manipulating the antiparkinsonian drug regimen, but this frequently
      worsens motor function. Atypical antipsychotics such as clozapine have been
      successfully employed to treat the psychosis without worsening the motor
      disability. Patient intolerance of clozapine therapy has prompted open-label
      studies with newer agents such as risperidone, remoxipride, zotepine, mianserin
      and ondansetron.

PMID- 9143859
TI  - Neuro-psychiatric effects of antimalarials.
AB  - OBJECTIVE: To study the neuro-psychiatric adverse effects of antimalarial drugs.
      SETTING: Persons who visited a Travel Clinic in Rotterdam over a period of 3
      months. DESIGN: Prospective cohort study on 394 persons taking mefloquine, 493
      persons taking proguanil and 340 persons not taking antimalarial drugs who
      visited Africa, South America, Asia, or the Middle East. METHODS: All persons
      received a structured questionnaire within 14 days of their return to the
      Netherlands. The questionnaire consisted of questions regarding use of alcohol,
      smoking, general health, medical history, tropical diseases during the trip, and
      other medicines, and contained an extensive list of general complaints regarding
      all body systems at four levels of severity. A modified and validated version of
      the Profile of Mood States was included. RESULTS: In the study period, 2541
      persons visited the Travel Clinic, of whom 1791 (70%) were both eligible and
      willing to co-operate. Of these 1791, data were obtained from 1501 (84%).
      Insomnia was most frequently encountered in users of mefloquine and mouth ulcers
      in proguanil users. After adjustment for gender, age, destination, and alcohol
      use, the relative risk for insomnia to mefloquine versus non-users of
      antimalarials was 1.6, and the excess risk was 6 per 100 users over an average
      period of 2 months. There were no significant differences between groups in
      depression, anxiety, agitation, and confusion. Stratification by gender
      demonstrated that insomnia was more common in women on mefloquine, but not in
      men. Also, women more frequently mentioned palpitations as an adverse event.
      After adjustment for age, destination, and alcohol use in women, the relative
      risks for insomnia and palpitations to mefloquine versus non-use of antimalarials
      were 2.4, and 22.5, respectively. When travellers were specifically asked for the
      adverse reactions they had experienced, anxiety, vertigo, agitation, and
      nightmares were significantly more frequently mentioned by mefloquine users.
      CONCLUSION: Insomnia was more commonly encountered during use of mefloquine than
      proguanil or during non-use of antimalarials.

PMID- 9143860
TI  - The acute effects of intravenously administered mibefradil, a new calcium
      antagonist, on the electrophysiologic characteristics of the human heart.
AB  - OBJECTIVE: This multicenter, double-blind, placebo-controlled, parallel-group
      study was designed to assess the acute effects of intravenous mibefradil on the
      electrophysiologic characteristics of the human heart. METHODS: Seventy-one
      patients referred for routine electrophysiologic testing were randomized to
      receive one of three intravenous treatments: placebo n = 23, 15 mg mibefradil in
      15 min followed by 25 mg in 60 min (group 1, n = 24), or 35 mg mibefradil in 15
      min followed by 45 mg in 60 min (group 2, n = 24). Electrophysiologic evaluations
      were performed prior to study drug administration and 30 min after the start of
      the infusion. Plasma samples were obtained at the start of the infusion and after
      15, 75, and 105 min. RESULTS: Sinus node recovery time decreased significantly in
      Group 1 patients (-103 ms). Corrected sinus node recovery time in group 2
      patients was 68.7 ms (P = 0.053). Compared to placebo, mibefradil produced mild
      but significant slowing of conduction in group 2 patients as manifested by an
      increase in the AH interval of 6.7 ms. Atrioventricular (AV) nodal refractoriness
      was increased, as indicated by a prolongation of the Wenckebach point in patients
      in both group 1 (32.1 ms) and group 2 (32.5 ms), compared to placebo. All adverse
      events were classified as mild to moderate and only one event (vasovagal attack)
      was considered to be treatment related. CONCLUSIONS: At plasma levels close to
      those found after chronic oral administration of 50 and 100 mg mibefradil, the
      higher dose produced an increase in corrected sinus node recovery time.
      Mibefradil also produced small but significant effects on AV nodal conduction and
      increased AV nodal refractoriness. Mibefradil had no effect on any other
      electrophysiologic parameter and was well tolerated.

PMID- 9143861
TI  - Metabolic effects of carvedilol in hypertensive patients.
AB  - OBJECTIVE: Fifty-six patients with essential hypertension were recruited to study
      the metabolic effects of carvedilol, a non-selective beta-adrenoceptor-blocker
      with alpha 1-adrenoceptor blocking properties. METHODS: The study started with a
      single-blind, 4-6-week placebo-treatment period followed by an open 6-month
      active treatment period. There was an option to increase the dose from 25 mg
      carvedilol to 50 mg daily after 6 weeks. Metabolic investigations were carried
      out at the end of the placebo period and at the end of the active treatment
      period. RESULTS: The results show that during carvedilol treatment blood pressure
      was efficiently lowered. The increase in very low density lipoprotein
      triglyceride concentration was 13%. Despite this modest increase high density
      lipoprotein cholesterol was reduced by 11%. The metabolic clearance rate of
      glucose at the hyper-insulinemic clamp test (adjusted for the prevailing insulin
      and glucose concentrations) decreased by 17%. At the i.v. glucose tolerance test
      the insulin area under the curve was increased by 18% and the glucose area by
      10%. CONCLUSION: The alpha 1-adrenoceptor-blocking characteristics of carvedilol
      probably explain the moderate changes of lipoprotein concentrations and insulin
      sensitivity gained compared with what is usually obtained with a non-selective
      beta-adrenoceptor-blocker.

PMID- 9143862
TI  - Acute effects of celiprolol on muscle blood flow and insulin sensitivity: studies
      using [15O]-water, [18F]-fluorodeoxyglucose and positron emission tomography.
AB  - OBJECTIVE: Recently the role of peripheral vasoconstriction in the aetiology of
      insulin resistance has been proposed. Celiprolol is a beta 1-selective
      adrenoceptor antagonist with partial agonist activity at the beta 2-receptor as
      well as vasodilator properties. The acute effects of celiprolol on skeletal
      muscle blood flow and insulin sensitivity were measured in this study. METHODS:
      Celiprolol (2 times 0.5 mg.kg-1) or saline was given intravenously to five
      healthy males in random order. Muscle blood flow was measured in femoral regions
      using [15O]-labelled water and positron emission tomography (PET) during
      euglycaemic hyperinsulinaemia (serum insulin approximately 65 mU.1(-1)) after an
      overnight fast. Thereafter, skeletal and heart muscle glucose uptake were
      determined using [18F]-2-deoxy-D-glucose. RESULTS: Celiprolol increased muscle
      blood flow by 74%, from 3.4 to 5.9 ml.min-1.100 g-1 muscle in the basal state. It
      decreased peripheral resistance by 40%, from 32.0 to 19.2 mmHg.ml-1.min-1.100 g
      1. Celiprolol significantly decreased diastolic blood pressure from 82 to 73 mmHg
      and increased heart rate from 61 to 68 beats.min-1, which suggests sympathetic
      activation. Insulin-stimulated glucose uptake was reduced by 46% in the whole
      body, from 39 to 21 mumol.kg-1.min-1 and by 59% in the femoral muscles, from 99
      to 41 mumol.kg-1.min-1, with celiprolol as compared to saline. The effect on
      heart glucose uptake did not statistically differ between the treatments.
      CONCLUSION: Celiprolol given intravenously increased muscle blood flow and
      decreased peripheral resistance at rest. It also acutely increased heart rate
      probably via sympathetic activation, and decreased insulin sensitivity in the
      muscles of healthy male volunteers. The enhanced muscle perfusion when celiprolol
      is given intravenously does not explain the improved insulin sensitivity seen in
      the long-term oral use in dyslipidaemic hypertensive patients.

PMID- 9143864
TI  - Age-dependent differences in the anticoagulant effect of phenprocoumon in
      patients after heart valve surgery.
AB  - OBJECTIVE: An enhanced response to warfarin and an increased risk of major
      bleeding has been observed in older patients. The reason for this increase in
      sensitivity remains unknown. It could be due to pharmacodynamic reasons,
      pharmacokinetic reasons, or both. METHODS: We therefore followed an anticoagulant
      regimen with phenprocoumon in 19 older (76 years) and 19 younger patients (50
      years) following heart valve replacement. INR values were determined frequently.
      At the 4th and around the 24th day after starting treatment with phenprocoumon,
      we also measured the total and unbound plasma concentration of phenprocoumon.
      RESULTS: The dose requirement to obtain the desired anticoagulant effect was
      significantly lower in the older patients than in the younger patients (26.3 vs.
      37.3 micrograms.kg-1.day-1). The total plasma concentration (2.19 vs. 2.43
      micrograms.ml-1), the percentage unbound drug in the plasma (0.61 vs. 0.64%) and
      the unbound plasma concentration (13.8 vs. 15.1 ng.ml-1) did not differ
      significantly between older and younger patients. The dose-adjusted INR
      (INR/dose) was higher in the older patients (110 vs. 67) but the INR adjusted for
      the unbound plasma concentration (INR/Cuss) which reflects the intrinsic
      sensitivity to the drug, was not significantly different (192 vs. 173). However,
      the older patients had an about 30% significantly lower metabolic clearance based
      on unbound drug (84 vs. 115 ml.kg-1.h-1). CONCLUSIONS: Older patients (> 70
      years) require a dose approximately 30% lower than younger patients (< 160
      years). Pharmacokinetic reasons (reduced metabolic clearance) are mainly
      responsible for the lower dose requirement of the older patients after heart
      valve surgery.

PMID- 9143863
TI  - Chronic colchicine treatment does not impair glucose tolerance in familial
      Mediterranean fever patients.
AB  - OBJECTIVE: To investigate a long-term colchicine treatment in inhibiting normal
      release of insulin, in response to a glucose load. SETTING: The Heller Institute
      of Medical Research, Sheba Medical Center, Tel-Hashomer. PATIENTS: Thirty-one
      familial Mediterranean fever (FMF) patients, treated continuously with colchicine
      (1.0-2.0 mg.day-1) for 2-13 years. METHODS: A standard oral glucose tolerance
      test (OGTT) was performed to study the effect of long-term colchicine treatment
      on glucose-induced insulin response. An intravenous glucose tolerance test
      (IVGTT) was then performed on randomly chosen FMF patients (n = 9) and age
      matched controls (n = 5). Glucose was administered 30 min after intravenous
      colchicine (2 mg) infusion. The sum of 1st- and 3rd-min insulin levels served as
      an index of early-phase insulin release. RESULTS: Based on the Office Guide to
      Diagnosis of Glucose Intolerance [13], one subject exhibited impaired glucose
      tolerance and two others had abnormal dynamics of glucose during the test but
      normal values at 120 min. Insulin values were normal in all participants. No
      significant differences were found in maximal glucose and insulin concentration,
      nor in the insulin release index between FMF colchicine-treated and healthy
      controls. CONCLUSIONS: Based on these findings, no impairment in glucose dynamics
      could be demonstrated in chronically colchicine treated patients, compared to
      untreated controls.

PMID- 9143865
TI  - Falsified or forged medical prescriptions as an indicator of pharmacodependence:
      a pilot study. Community pharmacists of the Midi-Pyrenees.
AB  - OBJECTIVE: While data on drug abuse liability have been determined for selected
      drugs in experimental studies, there is limited information available about drug
      abuse in real life. This study presents the results of a simple experimental
      epidemiologic survey of prescription forgeries in community pharmacies in the
      Midi-Pyrenees area (southwest France). During four periods (September-October
      1991, January-June 1992, September-October 1992 and January-June 1993), resident
      pharmacy students in several volunteer pharmacies were asked to complete a
      specific report form for each suspect prescription request. The main criteria
      used to identify forgeries were: inadequate dosage, multiple use of the
      prescription form, drafting not in accordance with the rules of prescription or
      false prescription forms (stolen prescription forms, photocopies). RESULTS: A
      total of 165 falsified prescriptions were collected. The 305 drugs involved in
      these forged prescriptions were opiate analgesics, benzodiazepines, amphetamines
      and minor opiate analgesics. Medications were essentially buprenorphine,
      flunitrazepam (in 2 mg dosage), phenobarbitone+amphetamine and chlorazepate.
      CONCLUSION: These results suggest that forged prescriptions can be used as an
      indicator of potential abuse liability of marketed psychoactive drugs. Although
      this survey cannot describe the real prevalence of the misuse or abuse of drugs,
      it constitutes a useful warning epidemiologic system to elicit early observations
      regarding new misuses of drugs as they are requested at the pharmacy.

PMID- 9143866
TI  - Different effects of inhibitors on the O- and N-demethylation of codeine in human
      liver microsomes.
AB  - OBJECTIVE: The O- and N-demethylation of codeine is catalysed by CYP2D6 and
      CYP3A4 respectively. The formation rates of morphine by O-demethylation and
      norcodeine by N-demethylation were studied in two sets of human liver microsomes.
      RESULTS: Relatively high K(m) values were found for both O- and N-demethylations,
      suggesting a low affinity to the corresponding enzymes. The inhibitory effects of
      various drugs were found to be different for O- and N-demethylations. The
      substrates of CYP2D6 such as thioridazine, amitriptyline and metoprolol inhibited
      the O-demethylation of codeine preferentially, while the substrates of CYP3A4
      such as cyclosporine A, midazolam and erythromycin were all strong inhibitors of
      the N-demethylation of codeine. Quinidine and lignocaine, although they are
      substrates of CYP3A, showed preferential inhibition over the O-demethylation of
      codeine, suggesting a low affinity to the CYP3A. Methadone and dextropropoxyphene
      showed a preferential inhibition of CYP2D6 over CYP3A, while theophylline did not
      inhibit the O- or N-demethylation to a greater extent. CONCLUSION: It seems that
      there was a good correspondence between the capacity of drugs to inhibit the O-
      and N-demethylation of codeine in human liver microsomes and their apparent
      metabolism by CYP2D6 or CYP3A4, respectively in vivo in man, suggesting that this
      in vitro inhibition test may be a useful screen for drugs which interact with
      these two important drug-metabolising enzymes.

PMID- 9143867
TI  - The pharmacokinetic and pharmacodynamic interaction between zileuton and
      terfenadine.
AB  - OBJECTIVES: The effects of zileuton on terfenadine pharmacokinetics, and the
      effects of terfenadine alone and the combination on the duration of the QTc
      interval and the morphology of the TU complex were examined. METHODS: The study
      was double-blind, randomized, placebo-controlled, two period cross-over in 16
      healthy volunteers. During each period, subjects received 60 mg of terfenadine
      every 12 h on days 1 to 7 and 600 mg of either zileuton or placebo for zileuton
      every 6 h on days 1 to 10. Blood samples were obtained on days 7 to 10 and serial
      ECGs were performed on days -1 and 7 in both periods. RESULTS: The combination of
      zileuton and terfenadine was well tolerated. Coadministration of zileuton with
      terfenadine resulted in a significant increase in the mean AUC and Cmax of
      terfenadine by approximately 35% and the mean AUC and Cmax of carboxyterfenadine
      by approximately 15%. The maximum concentration of terfenadine observed in the
      study was 9.6 ng.ml-1. The addition of zileuton to terfenadine did not result in
      significant changes in the evaluated ECG-recordings (QTc interval and morphology
      of TU complex). The difference in means for both maximum and average QTc interval
      was very small (< or = 2.3 ms), and there were no clinically significant changes
      in individual values. CONCLUSIONS: The relatively small pharmacokinetic effect of
      zileuton on terfenadine metabolism, with no change in the QTc interval, is
      unlikely to be of clinical significance. The interaction is minimal in comparison
      to the background variability of the population.

PMID- 9143868
TI  - Formulation of diltiazem affects cyclosporin-sparing activity.
AB  - OBJECTIVE: To consider the effect of changing from a conventional release
      formulation of diltiazem to the controlled diffusion diltiazem formulation on the
      cyclosporin-sparing effect in kidney transplant recipients. METHODS: Seven stable
      renal transplant recipients were studied on two separate occasions following at
      least 2 weeks stabilisation on either formulation. The order of administration of
      the two formulations was not randomised as all patients were already prescribed
      lower dosages of diltiazem before entering this phase of a larger study. The
      doses of diltiazem used were 90 mg (conventional release diltiazem) taken twice
      daily and 180 mg controlled diffusion diltiazem taken in the morning. RESULTS:
      Whilst there were no overall significant differences between the two
      formulations, the study demonstrated considerable interpatient variability when
      changing to the controlled diffusion formulation, particularly following the
      morning cyclosporin dose, with three patients showing a reduced cyclosporin AUC
      (30-60%) and one an increased cyclosporin AUC of 36%. CONCLUSION: A change in
      formulation of the cyclosporin-sparing agent may result in unpredictable
      alterations in cyclosporin concentrations and resultant clinical sequelae.

PMID- 9143869
TI  - Comparative study of four different pharmacokinetic computer programs: case study
      of a factor VIII preparation.
AB  - OBJECTIVE: To compare the pharmacokinetic parameters after a single dose of a
      monoclonally purified factor VIII concentrate in four different computer programs
      for pharmacokinetic analysis. SETTING: Haemophilia unit of a tertiary care
      university hospital. METHODS: Ten patients with severe haemophilia A were
      administered a single dose of 30-50 IU kg-1 body weight. Blood samples were drawn
      at different times during the first 48 h after infusion of factor VIII. Plasma
      factor VIII activity was measured by standard one-stage clotting assay and
      experimental data were analysed using four computer programs: JANA, PKCALC, F8SD
      and PCNONLIN. The pharmacokinetic models of analysis employed in the study were
      both compartmental and non-compartmental. The parameters compared were half-lives
      (t1/2) and mean residence time (MRT), volumes of distribution (V) and clearance
      (CL). Values obtained for each pharmacokinetic parameter in each program for the
      same model were tested for differences with a multiple analysis of variance
      (MANOVA). Linear correlation with the equivalent parameters for each program was
      also performed. RESULTS: Pharmacokinetic parameters differed depending on the
      computer program used to analyse the same data set. There were differences of
      statistical significance in t1/2 and V for one-compartment and two-compartment
      models derived by some of the programs, but none with the non-compartmental one.
      CL, considered model independent, showed differences between the programs
      evaluated. Correlations for each parameter generated were in general good (P <
      0.05). CONCLUSION: Pharmacokinetic parameters differed depending on the computer
      program used to analyse the same data set. The same patient data used in
      different computer programs will result in significantly different parameter
      estimations, although the non-compartmental approach is less affected by
      variation, and this should be taken into consideration for comparative purposes,
      for the development of new preparations and for the implications in patient care
      and therapy monitoring.

PMID- 9143870
TI  - Disopyramide concentrations in human plasma and saliva: comparison of
      disopyramide concentrations in saliva and plasma unbound concentrations.
AB  - OBJECTIVE: This study was performed to investigate whether it is possible to use
      saliva instead of blood usually used for therapeutic drug monitoring (TDM) of
      disopyramide. METHODS: Six healthy male volunteers ingested 200 mg of
      disopyramide base, and the disopyramide concentrations in saliva and plasma
      (total and unbound) were determined by the HPLC. RESULTS: Disopyramide
      concentration-time profiles for the saliva were nearly equal to those for the
      plasma unbound concentrations. A large variation for absorption time of the drug
      was observed among the subjects. Disopyramide concentrations (Cs) in saliva did
      not correlated well with plasma total concentrations (Cp), r = 0.799, but did
      well with unbound concentrations (Cpu), r = 0.969, for the 3-12 h period on the
      elimination phase. The mean ratio of disopyramide concentrations in the saliva
      against the plasma unbound concentrations was almost constant (1.02(0.10), CV =
      9.7%) for the period. The pharmacokinetic parameters (tmax, t1/2, AUC, AUMC and
      MRT values) for disopyramide calculated from the saliva data were nearly equal to
      those from the unbound data. CONCLUSION: Disopyramide concentrations in saliva
      correlated well with plasma unbound concentrations on the elimination phase.

PMID- 9143871
TI  - Simulation of the onset of neuromuscular block based on the early oscillations in
      the arterial plasma concentrations.
AB  - OBJECTIVE: The aim of the study was to describe by simulation the true plasma
      concentrations of non-depolarizing muscle relaxants (NDMRs) as a continuous
      function of time. In contrast to standard pharmacokinetic analysis of the time
      course of action via extrapolated plasma concentrations, the derived curve was to
      reflect zero plasma concentration initially and one or more cycles of peaks and
      troughs subsequently. We desired to study the influence of the initial delay and
      the early oscillations in the plasma concentrations on the time to onset of peak
      but submaximal neuromuscular block (NMB). Hypothetical NDMRs were postulated to
      display in humans a pattern of early arterial plasma concentrations similar to
      the reported pattern of indocyanine green plasma concentrations in dogs (an
      initial delay period and subsequent peaks and troughs). METHODS: Two hypothetical
      NDMRs with either a very rapid or a slow decay in plasma concentrations were used
      for the simulations. A delay and oscillations were imposed on a multiexponential
      function for the plasma concentrations of the NDMRs by an additional,
      biexponentially dampened sinusoid function. The time between intravenous bolus
      administration of the NDMRs and the first rise in plasma concentrations was fixed
      at 0.2 min. As experimentally observed with indocyanine green in dogs, the
      oscillations were limited to the first minute after injection. The NDMRs were
      simulated to diffuse from plasma into and out of the interstitial space of
      muscles according to a rate constant and the concentration gradient. The NDMRs
      were postulated to have free access from the interstitial space to the receptors,
      and the neuromuscular block was calculated using the Hill equation. RESULTS: The
      delay and the peak and trough plasma concentrations during the first minute after
      bolus injection of the NDMRs were simulated well by the postulated dampened
      sinusoidal function. The times to peak submaximal NMB and the equieffective doses
      were similar whether calculated on the basis of oscillatory or extrapolated
      multiexponential functions. Both simulations demonstrated that a rapid initial
      decay of the plasma concentrations is associated with a slightly faster onset of
      peak NMB and a slightly higher equieffective dose. CONCLUSION: Consideration of
      early oscillations in the plasma concentrations of a NDMR barely alters the
      simulated time course of action from that simulated by an extrapolated
      multiexponential function.

PMID- 9143872
TI  - Pharmacokinetics of an antifibrotic agent, pirfenidone, in haemodialysis
      patients.

PMID- 9143873
TI  - Interaction between cyclosporine A and midecamycin.

PMID- 9143874
TI  - Myelinogenesis in the optic nerve of (C57BL x CBA) F1 hybrid mice: a morphometric
      analysis.
AB  - Myelinogenesis in the optic nerve of the mouse begins by the end of the first
      week of postnatal life and proceeds well into adulthood. The optic nerve from
      different postnatal age groups of (C57BL x CBA) F1 hybrid mice was analysed
      ultrastructurally and morphometrically. Features examined were the myelinated and
      unmyelinated nerve fibres, mean myelinated nerve fibre diameter, myelinated nerve
      fibre diameter spectrum, number of myelin sheath lamellae in relation to fibre
      diameter and age. Results obtained showed that the optic nerve of the mouse is
      populated entirely by unmyelinated nerve fibres at birth. Myelinogenesis begins
      at about the fifth postnatal day (pnd), with clearer evidence by the 6th pnd. It
      starts selectively with the largest fibres and then progresses to involve other
      fibres of decreasing diameter. After the onset, myelinogenesis progresses with
      increasing rapidity, becoming most intense from the second week up to the fifth
      week, so that by the end of the fifth week about 73% of fibres have become
      myelinated. From then onward, the process proceeds at a progressively diminishing
      rate until, by the 16th week, virtually all the remaining 27% fibres are
      myelinated. At onset, the myelin sheath is loosely wrapped around the axons, but
      with increasing age the myelin lamellae become more compact around the axons. The
      population of unmyelinated fibres continued to diminish so that at the completion
      of the process (16th week), they were only very rarely encountered.
      Myelinogenesis in the optic nerve of the mouse appears to follow a similar course
      to that seen in other central tracts having a similar fibre diameter spectrum.

PMID- 9143875
TI  - The plasma membrane transformation does not last: microvilli return to the apical
      plasma membrane of uterine epithelial cells after the period of uterine
      receptivity.
AB  - Transmission electron microscopy was used to investigate morphological changes in
      surface ultrastructure of rat uterine luminal epithelial cells and to determine
      how quickly and to what extent microvilli return to the apical surface after the
      period of uterine receptivity for blastocyst attachment. Major, observable,
      differences in the surface morphology of uterine epithelial cells from six groups
      of pregnant rats were found. On the afternoon of day 6 of pregnancy, the apical
      surface is typically flattened and consists mostly of irregular projections, but
      by the morning of day 7, short, irregular microvilli are already evident among
      the remaining irregular projections giving the cell surface a 'taller' profile.
      By the afternoon of day 7, the microvilli have increased in height and frequency.
      This trend continues until by day 9 of pregnancy, the apical surface bears
      microvilli that are long, thin, and comparatively regularly distributed. These
      ultrastructural alterations demonstrate that the plasma membrane transformation
      of early pregnancy which is essential for uterine receptivity for blastocyst
      attachment, is transient and is followed by the return of regular microvilli.

PMID- 9143876
TI  - On the development of Cetacean extremities: I. Hind limb rudimentation in the
      Spotted dolphin (Stenella attenuata).
AB  - The Cetacea are group of animals which have completely lost their hind limbs
      during the course of evolution as a result of their entirely aquatic mode of
      life. It is known, however, that during their embryonal period, the hind limb
      buds are temporarily present. The control mechanisms of this regression are not
      yet understood, and vestigial limbs can sometimes be found in adults. The aim of
      the present study is to describe the course of hind limb rudimentation during
      prenatal development of Stenella attenuata (Spotted dolphin) at tissue and cell
      levels and compare the results with other natural or experimentally induced
      amelias. Hind limb buds of dolphin embryos, CRL 10-30 mm, were examined
      histologically. Before total disappearance, they show histodifferentiation
      comparable with other mammals. Initially, they form the apical ectodermal ridge,
      which soon regresses. The mesenchyme undergoes the process of condensation to
      form anlagens of prospective skeletal elements. These condensations are
      surrounded by vascular plexuses. During the course of rudimentation, some
      mesenchymal cells die, while the others are incorporated into the body wall.
      Nerve ingrowth into rudimentary limb buds was also detected. The temporary
      presence of hind limb rudiments in cetacean embryos can be regarded as a good
      example of recapitulation of phylogenesis in ontogenesis.

PMID- 9143877
TI  - Analysis of partial 16S rRNA nucleotide sequences of Chlamydia pecorum and C.
      psittaci.
AB  - Partial 16S nucleotide sequences of Chlamydia psittaci isolates S26/3 (abortion),
      P94/1 (pigeon) and Chlamydia pecorum isolates W73 (enteric) and E58
      (encephalomyelitis) were determined. Analysis of these data indicates very high
      levels of interspecies sequence conservation, with C. psittaci being more closely
      related to C. pecorum than to C. pneumoniae or C. trachomatis. Restriction enzyme
      analysis of nucleotide sequences indicated that BslI can be used to clearly
      distinguish C. psittaci and C. pecorum isolates. Psittacine and non-psittacine
      (pigeon) avian isolates of C. psittaci were distinguished using MaeI.

PMID- 9143878
TI  - DNA-based immunization induces anti-CD4 antibodies directed primarily to native
      epitopes.
AB  - DNA-based immunization is one of the most promising strategies to induce
      protective immunity against a variety of pathogens, presenting clear advantages
      as compared to the use of recombinant antigens. One of these advantages might be
      the ability to induce antibodies directed primarily against conformational
      determinants, as compared to immunization with recombinant proteins. To test this
      possibility, we have analyzed the antibody responses induced in mice by
      immunization with either recombinant soluble CD4 (rCD4) or by immunization with
      plasmid DNA-encoding CD4 (CD4-DNA). Mice immunized with CD4-DNA had lower titers
      of antibodies able to recognize rCD4 than mice immunized with rCD4. However,
      immunization with CD4-DNA induced antibodies reactive with the native cell
      surface CD4 molecule in all mice, whereas only two out of five mice immunized
      with rCD4 produced antibodies reactive with cell surface CD4, thus demonstrating
      that the genetic immunization approach may lead to an antibody response more
      consistent and superior at a qualitative level as compared to immunization with
      the corresponding recombinant protein. In addition, differences in the kinetics
      of appearance of antibodies directed against the native CD4 molecule were
      observed between mice immunized with CD4-DNA or rCD4. In the first case,
      antibodies reacting with cell surface CD4 were present 28 days after the first
      immunization, whereas mice immunized with rCD4 produced antibodies directed
      against the native molecule only following a booster injection. Finally, the two
      groups of mice produced antibodies with a different isotype distribution. No
      clear predominance of a specific IgG subclass was detected in the antibody
      population produced in response to DNA immunization. Conversely, mice immunized
      with rCD4 produced predominantly antibodies of the IgG1 isotype, indicating
      generation of a TH2 response. Together, results from this study indicate that the
      CD4 molecule endogenously produced following DNA immunization is expressed, at
      least partially, in a native conformation. This feature confers a major advantage
      to the DNA immunization approach as compared to immunization with the
      corresponding recombinant protein, which seems to elicit antibodies predominantly
      directed to epitopes uniquely expressed on the recombinant molecule.

PMID- 9143879
TI  - Plasmids and Aeromonas virulence.
AB  - Most putative virulence determinants of Aeromonas species are chromosomally
      encoded. However, several recent reports have indicated that some may be carried
      on or regulated by plasmids. Therefore, we examined the plasmid carriage rate of
      a total of 140 clinical and environmental Aeromonas isolates. Plasmid carriage
      was compared with the ability of an isolate to produce toxins and adhere to HEp-2
      cells. Overall, plasmid incidence in Aeromonas species was low (23/140, 16%) and
      independent of the source of the isolate. Plasmids were, however, more common in
      environmental isolates of A. veronii biovar sobria than in clinical isolates of
      this species (P < 0.05). We could find no evidence to support the recent
      literature findings that plasmids may have a role in Aeromonas virulence.

PMID- 9143880
TI  - Induction of an epitope-specific humoral immune response by lipopeptide-hapten
      conjugates: enhancement of the anti-melittin response by a synthetic T helper
      (Th)-cell epitope.
AB  - Lipopeptides of bacterial origin constitute potent immunoadjuvants when combined
      with antigens. After the immunization with lipopeptides covalently coupled to non
      immunogenic low-molecular-mass antigens or haptens, a hapten-specific humoral
      immune response can often be obtained. The response against synthetically
      prepared melittin fragments was further enhanced by the additional introduction
      of a T helper (Th)-cell epitope into the lipopeptide-hapten conjugate. The Th
      cell epitope applied, which is presented by the MHC class II molecule of the
      BALB/c (H-2d) haplotype, consisted of a synthetic 16-amino-acid oligopeptide
      derived from sperm whale myoglobin. The immune-enhancing effect was most
      pronounced for the melittin-derived peptide fragments [Mel(1-16)] and [Mel(17-26)
      CONH2]. Antibodies obtained after 3 immunizations with the conjugates recognized
      the synthetic as well as the native melittin molecule. Our results show that it
      is possible to markedly enhance a weak hapten-specific immune response by
      coupling the haptens to a lipopeptide conjugated to a haplotype-specific T helper
      cell epitope. The novel conjugates are well suited for the optimization of
      immunization procedures, and for the development of novel synthetic vaccines.

PMID- 9143881
TI  - Distribution, cloning, characterisation and mutagenesis of sodC, the gene
      encoding copper/zinc superoxide dismutase, a potential determinant of virulence,
      in Haemophilus ducreyi.
AB  - The sodC gene encoding the periplasmic enzyme copper/zinc superoxide dismutase
      (CuZnSOD) has been cloned from Haemophilus ducreyi, the causative agent of the
      genital ulcer disease, chancroid. Examination of a collection of diverse strains
      indicates that it is present throughout the species. Cloned sodC has been
      expressed in E. coli and shown to encode active enzyme. Insertional mutagenesis
      was used to construct a non-functional version of the gene. This has been
      transferred into the chromosome of the parent H. ducreyi strain by
      electroporation and homologous recombination, in preparation for studies of the
      role of this enzyme in the interactive biology of the organism with its host,
      perhaps in protecting bacteria from superoxide radicals and their reactive
      progeny generated by neutrophils in the context of host defence.

PMID- 9143882
TI  - Enteropathogenicity of Aeromonas jandaei and A. trota.
AB  - An experimental study of five isolates of Aeromonas jandaei and 12 of A. trota
      was carried out to examine if they produced an enterotoxic substance, and if so,
      to characterise that factor and to see if it caused any mucosal damage. Only two
      of the A. trota strains caused fluid accumulation in the initial rabbit ileal
      loop (RIL) tests. The remaining strains did so only after one to five sequential
      passages through RILs and once they caused a secretory response they showed a
      gradual enhancement of fluid outpouring after each subsequent passage. Inocula of
      approximately 1 x 10(5) viable cells and 0.25 ml of culture filtrate caused fluid
      accumulations comparable to those of toxigenic V. cholerae 569B. The enterotoxic
      factors of both organisms were inactivated when held at 56 degrees C for 20 min
      or 65 degrees C for 10 min and showed biological activity over a wide range of
      pH. The only histopathological change observed in the ileal loop was depletion of
      mucus from the goblet cells. These data thus indicate that strains of A. jandaei
      and A. trota may produce a heat-labile and pH-stable diarrhoeagenic substance
      that causes little or no damage to the intestinal mucosa, like that of other
      known heat-labile enterotoxins.

PMID- 9143883
TI  - Virulent and avirulent Rhodococcus equi infection in T-cell deficient athymic
      nude mice: pathologic, bacteriologic and immunologic responses.
AB  - We investigated the pathologic, bacteriologic and immunologic responses of BALB/c
      nu/nu mice (nude mice) and BALB/c mice (euthymic mice) infected intravenously
      with virulent and avirulent Rhodococcus equi ATCC 33701, and its plasmid-cured
      derivative ATCC 33701P-, to evaluate the role of T lymphocytes. Adaptive transfer
      of immune and normal spleen cells into nude mice was also investigated. Nude and
      euthymic mice were inoculated with 10(6) ATCC 33701 or 10(6) ATCC 33701P-
      intravenously (i.v.) and killed at 0, 7, 14, 21, 28 and 35 days post-inoculation,
      except dead cases. In athymic nude mice infected with ATCC 33701, deteriorating
      systemic inflammatory responses developed during the experimental period and
      multiplication of the bacteria continued until the end of the experiment. Nude
      mice developed splenomegaly and multifocal gross hepatic necrosis with some
      mortality. Splenomegaly was caused by diffuse proliferation of bacteria-laden
      macrophages and epithelioid cells, and gross hepatic necrosis was caused by the
      formation of thromboses and granulomatous lesions. Infection of euthymic mice
      with a sublethal dose of ATCC 33701 resulted in transient granuloma formation in
      the liver and spleen, production of specific antibodies against the virulent
      bacteria and gradual elimination thereof. In contrast, infection with ATCC 33701P
      produced few lesions after rapid elimination and no antibody production against
      bacteria in either normal or athymic nude mice. In nude mice given normal and
      immune spleen cells, histopathological lesions and granulomas formed only in the
      liver and spleen, in addition to specific antibodies against 15- to 17-kDa
      antigens. The pathological lesions observed in the nude mice given immune spleen
      cells were similar to those seen in the mice given normal spleen cells, but they
      were less severe than those in mice given normal spleen cells. Mice given immune
      spleen cells showed a significantly higher elevation of antibody production than
      mice given normal spleen cells. These results suggested that protection against
      virulent R. equi in mice depends mainly on cell-mediated immune responses,
      whereas avirulent R. equi in mice are cleared by innate immune responses.

PMID- 9143884
TI  - Genotypic and phenotypic determination of five virulence markers in clinical
      isolates of Escherichia coli.
AB  - The presence of the virulence markers K1 capsule, serum resistance, aerobactin, S
      and P/PR fimbriae were examined in a total of 395 E. coli strains from different
      extraintestinal infections and in 81 faecal isolates of healthy volunteers using
      specific DNA probes and classical phenotypic methods. All markers were more
      frequently detected when genotypic assays were applied. The simultaneous
      occurrence of 3-4 virulence determinants was typical for isolates derived from
      patients with septicaemia or meningitis. Isolates from blood cultures and
      cerebrospinal fluid were expressing the virulence phenotypes to a greater extent
      than isolates from urine or faeces. The use of colony hybridization with specific
      oligonucleotide and polynucleotide probes for the detection of virulence
      determinants has been proven to be more specific and reliable than phenotypic
      approaches.

PMID- 9143885
TI  - Comparison of two botulinum-toxin preparations in the treatment of essential
      blepharospasm.
AB  - A double-blind study was performed on 212 consecutive patients (58 men, 154
      women) with essential blepharospasm, who received one injection of Botox and one
      injection of Dysport in two separate treatment sessions (at the first session the
      patients randomly received one of the drugs, at the second the other drug was
      given. The patients' mean age was 66.4 years +/- 8.14 (range 39-86 years). The
      average dose of Botox per treatment was 45.4 IU +/- 13.3 (range 25-85 IU) and of
      Dysport 182.1 IU +/- 55.1 (range 100-340 IU). We used an empirical ratio
      Botox:Dysport of 1:4 (IU) in order to ensure equal doses. All patients had
      received botulinum toxin injections prior to the present study (mean 15.3
      injections +/- 9.4; range 1-43 injections). The effect of Botox lasted 7.98 weeks
      +/- 3.8 (range 0-16 weeks), while the effect of Dysport lasted 8.03 weeks +/- 4.6
      (range 0-22 weeks). Side effects (ptosis, tearing, blurred vision, double vision,
      hematoma, foreign body sensation) were observed with Botox in 36 of 212 (17.0%)
      of the treatment sessions and with Dysport in 51 of 212 sessions (24.1%). Ptosis
      was observed with Botox in 3 cases (1.4%) and with Dysport in 14 cases (6.6%).
      There was no statistically significant difference in the duration of the
      treatment effect between the two preparations (P = 0.42). The total number of
      side effects was lower with Botox than with Dysport; the significance of the
      difference was moderate (P < 0.05). However, the rate of occurrence of ptosis was
      significantly lower with Botox (P < 0.01). The bioequivalence, which varies
      between 1:3 and 1:6 (Botox:Dysport) in the literature, was found to be 1:4 in
      this study.

PMID- 9143886
TI  - Increased intraocular pressure during treatment for chronic uveitis.
AB  - OBJECTIVES: (1) To prospectively evaluate the incidence of increased intraocular
      pressure (IOP) in patients suffering from chronic uveitis. (2) To identify the
      main factors responsible for an increase in the IOP among these patients.
      METHODS: Two hundred and one patients suffering from chronic uveitis were
      included. Enrolled patients had an initial IOP of 8-18 mmHg. The patients were
      treated and clinically monitored during a period of 4 years. The IOP was measured
      at each visit and its changes followed prospectively. All patients were followed
      up for at least 12 months after enrollment. RESULTS: Twenty-four (12%) of the 201
      patients had IOP higher than 24 mmHg at two or more consecutive visits. Of these
      24 patients, 19 suffered from bilateral uveitis and 5 had unilateral disease.
      Four of the 19 patients with bilateral uveitis developed a constant IOP higher
      than 24 mmHg in both eyes, while in 15 patients an IOP higher than 24 mmHg
      persisted only in one eye. A close association between the increased IOP and the
      use of corticosteroids was found in 18 of the 24 cases (75%). This association
      was ascertained in 16 of these patients by the decrease in IOP levels on
      discontinuation of the corticosteroid regimen and the renewed increase IOP was
      due to pupillary block in three cases (12.5%), to iris and angle
      neovascularization in two (8.3%), and to the inflammatory process per se in one
      case only (4.2%). CONCLUSIONS: This study demonstrates that a persistent
      elevation of the IOP in patients suffering from chronic uveitis is, in the
      majority of cases, associated with the use of corticosteroids.

PMID- 9143887
TI  - Double contour of the lens capsule edges after continuous curvilinear
      capsulorhexis.
AB  - BACKGROUND: After curvilinear capsulorhexis in cataract surgery often a double
      ring shape of the remaining capsular margins can be observed. In order to better
      understand this phenomenon we performed a histological study of excised capsules
      after continuous curvilinear capsulorhexis. METHODS: Ten anterior capsular
      specimens from cases with double-ring structure of the capsular margins after
      continuous curvilinear capsulorhexis (D-group) were examined light
      microscopically and compared with 10 normal cases (N-group) and 10 cases with
      pseudoexfoliation (P-group). Three cases from each group were also examined
      electron microscopically. RESULTS: A characteristic step formation in the
      capsular edges and in addition horizontal capsular splits in the border zone
      between the zonular lamella of the anterior capsule and the capsule proper could
      be demonstrated histologically in the D-group. CONCLUSIONS: There seems to be a
      weak point of the capsular tissue in the border zone between zonular lamella of
      the lens and the capsule proper. The superficial splits that we found
      histologically in this region might be a precursor or forme fruste of true
      exfoliation. The outward-directed traction force exerted by the zonular fibers
      seems to lead to further disruption in this weakened layer of the lens capsule
      during capsulorhexis, producing a double-ring contour of the capsular margins.

PMID- 9143888
TI  - Indirect scatter laser photocoagulation to subfoveal choroidal neovascularization
      in age-related macular degeneration.
AB  - BACKGROUND: Occult choroidal neovascularization (CNV), poorly defined on
      fluorescein angiography, is present in the majority of patients with exudative
      complications of age-related macular degeneration. For patients who present with
      this type of subfoveal CNV but who have useful visual acuity, no form of
      treatment is of proven benefit. Accordingly, a pilot randomized trial of indirect
      laser treatment was performed. The rationale of this treatment was to inhibit the
      CNV through laser-induced effects on the retinal pigment epithelium. METHODS:
      Patients with occult subfoveal CNV without retinal pigment epithelial detachment
      and with visual acuity of 20/200 or better were randomized to treatment or
      control groups. A grid of laser burns was applied to the macula beyond the area
      of serous retinal detachment and of angiographically defined occult CNV. RESULTS:
      After an average follow-up of 38 months, there was no difference in mean final
      visual acuity (0.12 treated, 0.14 control) or clinical outcome between treated
      and untreated groups. Fluorescein angiography showed gradual enlargement in the
      occult CNV in 58% of eyes in both groups. A decrease in visual acuity to worse
      than 20/200 (54% of treated, 50% of control eyes) was associated with ingrowth of
      well-delineated CNV (6 treated, 7 control eyes) or progression to a fibroglial or
      atrophic scar (11 treated, 8 control eyes). CONCLUSIONS: No benefit was
      demonstrated for scatter photocoagulation of the macula in patients with age
      related macular degeneration and occult subfoveal CNV with initially good visual
      acuity. There were, however, no complications related to treatment.

PMID- 9143889
TI  - Ascorbic acid and amino acid values in the aqueous humor of a patient with Lowe's
      syndrome.
AB  - BACKGROUND: Aminoaciduria is found in Lowe's syndrome. No studies of
      concentrations of ascorbic acid and amino acids in the aqueous humor of the
      syndrome have been performed. We examined these concentrations in a patient with
      Lowe's syndrome. METHODS: Ascorbic acid and amino acid levels in the aqueous
      humor and plasma of a male infant were measured by means of high-performance
      liquid chromatography. The patient, who had congenital cataract, miotic pupils,
      opaque corneas, glaucoma, aminoaciduria, normal levels of ascorbic acid and amino
      acid in the plasma, and renal tubular acidosis, underwent trabeculotomy,
      lensectomy, and anterior vitrectomy in both eyes. RESULTS: Intraocular pressure
      in both eyes decreased to within the normal range, but both corneas remained
      opaque. The amino acid levels in the aqueous humor were similar to those in the
      plasma, but intracameral ascorbic acid levels were decreased. After topical
      instillation of ascorbic acid, the corneas became transparent. The proband's
      mother had good visual acuity but paracentral lens opacities in both eyes. His
      maternal grandmother had scattered cortical opacities in both lenses. CONCLUSION:
      In this infant with Lowe's syndrome, we found intracameral levels of amino acids
      similar to those in the plasma. Levels of ascorbic acid in the aqueous humor were
      decreased.

PMID- 9143890
TI  - The expression of tenascin and fibronectin in keratoconus, scarred and normal
      human cornea.
AB  - BACKGROUND: The etiology and pathogenesis of keratoconus remain unclear, and
      therefore we decided to study the distribution of different isoforms of tenascin
      (Tn) and fibronectin (Fn) in normal human corneas and in those obtained from
      penetrating keratoplasty for keratoconus and corneal scarring. METHODS: Frozen
      sections of human cornea and conjunctiva were stained by immunohistochemical
      methods with a panel of monoclonal antibodies (MAbs) against different isoforms
      of Tn and Fn. RESULTS: In the normal human eye, Tn was found in the limbal and
      conjunctival basement membrane region, in the conjunctival blood vessels and at
      the junction of the cornea and sclera, but no immunoreaction was seen in the
      normal cornea. In the corneas from the keratoconus patients, a clear
      immunoreaction for Tn was seen in the defects of Bowman's membrane as well as in
      the distorted stroma beneath the defects. In some of the keratoconus corneas,
      basement membrane adjacent to the defects also showed reactivity for Tn, and in
      clinically and histologically scarred keratoconus corneas the scars expressed Tn.
      In the scarred corneas, only blood vessels in the posterior portion of the cornea
      showed immunoreactivity for Tn, while no Tn was noted in the scar area or in
      Bowman's membrane. No major differences were noticed in the reactivity of
      different MAbs against Tn isoforms. Fn, extradomain A Fn (EDA-Fn) and oncofetal
      Fn (onc-Fn) were found in the basement membrane of the central cornea of the
      normal eye. In keratoconus corneas, the defects and clinical and histological
      scars bound MAbs against Fn, EDA-Fn and onc-Fn, but in the scarred corneas no
      enhancement in the expression of Fns was noted. Extradomain B cellular Fn (EDB
      Fn) was not expressed in any of the eyes studied. CONCLUSIONS: The results
      suggest that the anterior portion of the cornea is involved in the pathogenesis
      of keratoconus. Furthermore, it seems that the expression of Tn and Fns in the
      clinically scarred keratoconus corneas is due to a process in which both
      repairing and scar-forming mechanisms operate at the same time. However, the
      origin of the defects in Bowman's membrane seen in keratoconus still remains
      unclear. They may be minor scars due to the disease or primary defects in the
      process leading to keratoconus.

PMID- 9143891
TI  - Endothelial cell death in organ-cultured donor corneae: the influence of
      traumatic versus nontraumatic cause of death.
AB  - BACKGROUND: Donors who have suffered a traumatic death are, on average, younger
      than those who have died from other causes, and the time from death to
      enucleation (DET) also tends to be shorter. Corneae obtained from such donors are
      therefore considered particularly suitable for grafting. One of the reasons for
      excluding a donor cornea from transplantation is the occurrence of endothelial
      cell necrosis during organ culture, and we investigated whether the incidence of
      this phenomenon bears a relationship to death by traumatic or nontraumatic means.
      METHODS: Data from 2125 donor corneae were collected using standardized
      evaluation protocols between January 1991 and December 1995 and included
      information on cause of death, age and DET, as well as endothelial cell loss and
      necrosis. Traumatic deaths were recorded in 346 cases, nontraumatic deaths in the
      other 1779 cases. Since differences in age (P = 0.006) but not in DET occurred
      within each of these groups, a more refined comparison, with matched data (< 35
      years), was also undertaken. RESULTS: Forty (11.6%) of the 346 corneae derived
      from traumatic death donors manifested total or partial endothelial cell death in
      organ culture. The corresponding figure in the nontraumatic death group was only
      105/1779 (5.8%; P = 0.0002). After matching for age, endothelial cell death
      during culturing was revealed in 18 (13.5%) of the 133 of the traumatic death
      corneae and in 3 (2.6%) of the 115 nontraumatic death ones (P = 0.004); the
      overall incidence of endothelial cell death (total or partial) during organ
      culture was 6.8% (145/2125). Endothelial cell loss during culturing of the 227
      age-matched donor corneae which still had an intact endothelial monolayer at the
      end of the incubation period was 340 +/- 388 cells/mm2 in traumatic death corneae
      (n = 115) and 255 +/- 318 cells/mm2 in nontraumatic death ones (n = 112; P =
      0.051). CONCLUSION: Corneae obtained from traumatic death donors were more liable
      to undergo total or partial endothelial cell death during organ culture than were
      those procured from nontraumatic death ones. However, in corneae which survived
      the period of culture, there was no significant difference in endothelial cell
      loss between the two groups. Whilst the mechanism underlying this increased
      susceptibility of traumatic death corneae to cell death remains elusive, the data
      gleaned from this investigation nonetheless emphasize the potential importance of
      being able to perform meaningful in vitro viability tests on donor corneae; this
      is possible only under organ culture conditions.

PMID- 9143892
TI  - Effects of mitomycin C on the expression of proliferating cell nuclear antigen
      after filtering surgery in rabbits.
AB  - BACKGROUND: The aim of the study was to evaluate the effects of mitomycin C on
      the cell replication activity in wound healing following experimental filtration
      surgery. METHODS: Trabeculectomy with or without application of mitomycin C was
      performed on albino rabbit eyes. At 1, 4, 7, 14, and 28 days after surgery, the
      expression of proliferating cell nuclear antigen, a marker of cell proliferation,
      in the filtering site was examined immunohistochemically using a streptavidin
      biotin complex method. RESULTS: In control eyes that underwent trabeculectomy but
      did not receive mitomycin C, the number of immunoreactive cells increased 4-7
      days after operation and decreased markedly at around 14 days. The filtering site
      was obstructed histologically at 4-7 days after operation. In the mitomycin C
      treated eyes, immunoreactive cells appeared 4 days after surgery but disappeared
      by 7 days at the surgical site. The number of immunoreactive cells in the treated
      eyes was much lower than that in control eyes. CONCLUSION: The cell replication
      activity was markedly inhibited by administration of mitomycin C. The filtering
      site remained open for 28 days after surgery, whereas it was completely
      obstructed within 7 days in control eyes. Immunocytochemistry for proliferating
      cell nuclear antigen, as used in this study, is a simple and reliable method for
      detection of cell replication activity.

PMID- 9143893
TI  - Deposition of extracellular matrix on intraocular lenses in rabbits: an
      immunohistochemical and transmission electron microscopic study.
AB  - BACKGROUND: We examined by transmission electron microscopy the accumulation of
      extracellular matrix on intraocular lenses (IOLs) implanted experimentally into
      rabbit eyes, and evaluated the immunolocalization of such extracellular matrix
      components as collagen types I, III, and IV, and cellular fibronectin on these
      IOLs. METHODS: Phacoemulsification and aspiration of the crystalline lens were
      performed and an IOL was implanted into the capsular bag of each eye of each of
      16 adult albino rabbits under general anesthesia. After up to 12 weeks, the
      animals were killed and the IOLs were removed. Specimens were processed for
      transmission electron microscopy or for immunohistochemical detection collagen
      types I, III, and IV, and cellular fibronectin. RESULTS: Transmission electron
      microscopy revealed an accumulation of extracellular matrix between the residual
      anterior lens capsule and the surface of an IOL explanted 4 weeks after surgery.
      Collagen types I and III and cellular fibronectin were detected
      immunohistochemically on each IOL in association with cellular deposits. Type IV
      collagen-immunoreactive matrix was not seen on the optic portion, but was
      detected on the haptic portion of one of six IOLs examined. CONCLUSION: Each
      component of the extracellular matrix that is deposited on the IOL supplies
      scaffolding for the adhesion and proliferation of cells. These components are
      considered to be produced by cells such as lens epithelial cells and macrophages
      that adhere to the IOL surface.

PMID- 9143894
TI  - Immunolocalization of ubiquitin and related enzymes in human retina and retinal
      pigment epithelium.
AB  - PURPOSE: To examine the localization of ubiquitin (Ub) and related enzymes in
      human retina with emphasis on the retinal pigment epithelium (RPE)-Bruch's
      membrane complex. METHODS: Thirty human eyes enucleated for various disease
      processes were examined. Immunohistochemistry was performed on paraffin sections
      using antibodies against Ub, Ub-conjugating enzyme (E2), Ub carboxyl-terminal
      hydrolase (PGP 9.5), and, for comparison, arrestin (Arr). Immunoreactivity (IR)
      was tested using the avidin-biotin method. RESULTS: Ub was present throughout
      retina but was particularly prominent in ganglion cells and RPE. Most intriguing
      was the presence of Ub IR in age-related, sub-RPE deposits such as drusen and
      basal laminar deposits (BLD). RPE immunolabeling was more intense in older
      tissue, but otherwise no pattern of Ub IR could be linked to specific diseases.
      E2 IR colocalized with Ub, with one exception; E2 IR was not found in drusen or
      BLD. PGP 9.5 IR was intense in nerve fibers, ganglion cells, and the inner
      nuclear and plexiform layers. RPE staining was faint and patchy; sub-RPE deposits
      were not labeled. Arr IR was present in photoreceptors but not within or beneath
      RPE cells. CONCLUSION: The ubiquitination process is important in human retina
      and particularly in ganglion cells. Ub-related processes are also active in RPE
      and may be involved in the degradation and disposal of proteins from these cells.
      The presence of Ub in sub-RPE deposits--without related Ub-processing enzymes-
      raises the possibility that certain proteins become ubiquitinated within RPE but
      that further degradation of the Ub-protein complexes does not occur.

PMID- 9143895
TI  - Pars plana vitrectomy for retinal detachment due to internal posterior
      ophthalmomyiasis after cataract extraction.
AB  - BACKGROUND: The authors report a case of posterior internal ophthalmomyiasis
      causing vitreous haemorrhage and retinal detachment after uncomplicated cataract
      extraction. CASE REPORT: The patient suffered an abrupt vitreous haemorrhage 9
      days after ECCE and posterior chamber IOL implantation. After 2 months the
      haemorrhage did not clear up and a retinal detachment arose. The patient
      underwent encircling scleral buckle, pars plana vitrectomy and fluid-gas
      exchange. In course of intervention the surgeon removed from the vitreous chamber
      a 14-mm-long round worm subsequently identified as a dipterous larva of the
      Sarcophagidae family. DISCUSSION: The patient showed no sign of subretinal
      tracking or retinal breaks or holes. The sclerocorneal surgical wound seems the
      most likely site of entrance of the parasite, and this would then be the first
      reported case of myiasis with no RPE tracking.

PMID- 9143897
TI  - Variables that influence consumers' inferences about physician ability and
      accountability.
AB  - Previous research has shown that the quality of interpersonal care provided by
      physicians is correlated with the initiation of malpractice litigation.
      Unfortunately, this research has not controlled for the effects of actual
      treatment quality or of health outcomes. The research on which this article is
      based experimentally manipulates three variables: (1) patient involvement with
      treatment decisions, (2) financial incentives by third party payers to encourage
      costeffective medicine, and (3) use of new treatment practices that have not been
      widely adopted by other physicians.

PMID- 9143898
TI  - Toward effective regional trauma networks: management auditing initiatives in
      Ontario.
AB  - Trauma is a significant multidimensional health problem in North America. An
      important organizational response to this problem has been the creation of
      regional trauma care systems. This article focuses on the need to assess the
      effectiveness of such systems from a regional management perspective.

PMID- 9143896
TI  - Endophthalmitis after Lasiodiplodia theobromae corneal abscess.
AB  - BACKGROUND: Lasiodiplodia theobromae is an exceptional cause of human
      keratomycosis. PATIENT: We treated a 53-year-old man with fungal keratitis, which
      had been treated with topical betamethasone and gentamicin for 1 month, and
      endophthalmitis due to Lasiodiplodia theobromae. Despite intensive systemic,
      topical and intravitreal fungicidal treatment, enucleation had to be performed.
      RESULTS: The vitreous aspirate cultures were negative as of the second
      amphotericin intravitreal injection. However, histology revealed that the fungus
      was present in the cornea, ciliary body, iris and retina. CONCLUSION: The use of
      topical steroids may worsen the outcome of the infection.

PMID- 9143899
TI  - Elderly patients' satisfaction with the outcome of their health care complaints.
AB  - This article profiles the determinants of elderly patients' satisfaction with the
      outcome of their health care complaints. Type of provider response, severity of
      complaint, and the individual characteristics of age and cognitive age were found
      to be significant in effecting satisfaction. Related strategies for managing
      elderly health care complaints are discussed.

PMID- 9143900
TI  - Integrated networks and health care provider cooperatives: new models for rural
      health care delivery and financing.
AB  - Minnesota's 1994 health care reform legislation authorized the establishment of
      community integrated service networks (CISNs) and health care provider
      cooperatives, which were envisioned as new health care delivery models that could
      be successfully implemented in rural areas of the state. Four CISNs are licensed,
      and three organizations are incorporated as health care provider cooperatives.
      Many of the policy issues Minnesota has faced regarding the development of CISNs
      and health care provider cooperatives in rural areas are similar to those raised
      by current Medicare reform proposals.

PMID- 9143901
TI  - Management retention contracts in health care affiliations.
AB  - This article traces the history and development of management retention contracts
      in health care, outlines the principal provisions contained in a management
      retention contract, and provides answers to frequently asked questions. The key
      advantage of management retention agreements is that they allow executives to be
      more dispassionate in their business decisions and remove psychological barriers
      to accepting a new arrangement, because their career concerns are addressed. At a
      time when hospitals are exploring significant affiliation, merger, or sale
      possibilities, these arrangements establish a method of ensuring that senior
      executives do not seek other employment or leave the hospital during the critical
      phases of corporate negotiation and preclosing.

PMID- 9143902
TI  - The valuation of health care intangible assets.
AB  - Health care entities (and especially medical practices) are valued for a number
      of reasons: sale transaction pricing and structuring, merger formation and
      dissolution, taxation and regulatory compliance, and litigation support and
      dispute resolution. The identification and quantification of the entity's
      intangible assets are often the most important aspects of the valuation. This
      article illustrates the generally accepted methods for valuing health care
      related intangible assets.

PMID- 9143903
TI  - Organizational tenure and the perceived importance of retention factors in
      nursing homes.
AB  - Health care organizations can avoid substantial turnover costs through retention
      strategies geared to the varying needs of employees. The study on which this
      article is based examined retention needs of registered nurses in nursing homes
      and found that they varied by tenure. Low tenure nurses preferred learning
      opportunities and advancement potential while high tenure nurses favored work
      flexibility. Implications for retention policy in nursing homes are discussed.

PMID- 9143904
TI  - Methods of measuring patient satisfaction in health care organizations.
AB  - Patient perceptions of the quality of services provided is a key factor (along
      with cost effectiveness) in determining a health care organization's competitive
      advantage and survival. This article examines the advantages, disadvantages, and
      problems associated with nine different methods of measuring patient satisfaction
      with service quality. The appropriateness of each of these techniques under
      different organizational conditions is also discussed. The article concludes with
      guidelines for measurement of patient satisfaction and implementation of
      managerial follow-up.

PMID- 9143905
TI  - The physician executive: role in the adaptation of American medicine.
AB  - In the arena of managed care and large delivery systems, professional
      associations find it increasingly difficult to influence the environments in
      which their members practice. Physician executives appear likely to play key
      roles in the response of medicine to change. This article discusses how an
      analysis of the work of physicians involved in management fails to yield a clear
      analytic distinction between physicians engaged in management and the behavior of
      others who have managerial responsibility.

PMID- 9143906
TI  - Progress in transcriptionally targeted and regulatable vectors for genetic
      therapy.
AB  - Safety is an important consideration in the development of genetic therapy
      protocols; for example, proteins that are therapeutic in the context of one
      tissue may be harmful in another. This is particularly relevant to suicide gene
      strategies for cancer, which require in vivo delivery of DNA and which, in
      general, demand that the therapeutic product be limited as far as possible to
      malignant cells. This has led to a requirement for "transcriptionally targeted"
      vectors that can restrict the expression of the therapeutic sequence to
      appropriate cells. Furthermore, there may be a therapeutic window for certain
      proteins such that levels of expression below and above certain thresholds may be
      ineffective or toxic, respectively. Therefore, it would also be desirable to
      create vectors that allow exogenous control of expression, so that levels of the
      therapeutic protein can be raised or lowered according to therapeutic need. In
      the context of transcriptional targeting, one may sometimes use cis-acting
      sequences to limit transgene expression to the target cell type. In genetic
      therapy for cancer, for example, it may be possible to identify and use
      transcriptional control elements that drive expression of proteins unique to, or
      over-expressed in, malignant cells. These controls would greatly reduce
      collateral expression of the transgene, and hence reduce toxicity to healthy
      cells. With regard to exogenous control of expression subsequent to transduction,
      several synthetic gene regulation systems have now been produced. In these
      systems, an inducer or repressor acts on a synthetic transcription factor that
      recognizes motifs unique to the promoter of the transgene; this allows regulated
      expression of the therapeutic protein without nonspecific effects on cellular
      promoters. It is likely that a vector will soon be produced in which tissue
      restricted expression of the synthetic transcription factor is combined with
      regulatable transgene expression thereby allowing precise control of therapeutic
      protein production in specific tissues via administration of an inducing or
      repressing agent.

PMID- 9143907
TI  - Surfactant inhibits cationic liposome-mediated gene transfer.
AB  - We have demonstrated that tracheal insufflation of recombinant plasmid DNA
      results in transfection of rat lungs to the same extent as insufflation of
      plasmid-cationic liposome complex. To understand this observation better, we
      investigated the in vitro gene transfer of plasmid DNA in the presence and
      absence of cationic liposome and the effect of surfactant on gene transfer. The
      chloramphenicol acetyltransferase (CAT) expression plasmids pBL-CAT and pSV-CAT
      were studied in three cell types: rat fetal lung fibroblast (RFL-6), calf
      pulmonary artery endothelial cell (CPAE), and rat type II alveolar epithelial
      cell (type II AE). Three cationic liposomes were tested: DDAB (dimethyl
      dioctadecyl ammonium bromide)-liposome, DOTAP (dioleoyltrimethyl ammonium
      propane)-liposome, and lipofectin. The results revealed that (i) plasmid DNA
      alone caused a dose-dependent, low-level transfection, most efficiently in RFL-6
      followed by CPAE and type II AE, (ii) DDAB-liposome markedly enhanced gene
      transfer, most efficiently in RFL-6 followed by CPAE and type II AE, (iii)
      Survanta, a naturally derived surfactant preparation, and Exosurf, a synthetic
      surfactant, while having no effect on in vitro gene transfer by plasmid DNA
      alone, markedly inhibited cationic liposome-mediated gene transfer, (iv)
      dipalmitoyl phosphatidylcholine was responsible for the inhibitory effect of
      Exosurf, and (v) inhibition of cationic liposome-mediated gene transfer by
      Exosurf was not due to inhibition of plasmid DNA-cationic liposome complex uptake
      or interference with the promoter and enhancer. The observed inhibition of
      cationic liposome-mediated gene transfer by surfactant may in part explain our
      previous observation that tracheal insufflation of plasmid DNA and plasmid
      cationic liposome complex results in equal lung gene transfer.

PMID- 9143908
TI  - Induction of the suicide HSV-TK gene by activation of the Egr-1 promoter with
      radioisotopes.
AB  - In investigating new methods for the treatment of pancreatic cancer, we have
      explored the possibility of using a combination of radiation and gene therapies.
      We demonstrate herein that the early growth response gene 1 promoter (Egr-1) is
      sufficient to confer selective expression of the luciferase gene (Luc) in a human
      pancreatic tumor cell line (AsPc-1) when exposed to ionizing radiation. The Egr-1
      promoter directed the radioinducible expression of luciferase, and yielded higher
      levels of Luc activity than that in nonirradiated lines. The radioisotopes Tc
      99m, I-131, and Ga-67-citrate were selected as Egr-1 activators for their
      potential to accumulate in tumors. We studied Ga-67-citrate, a radioisotope
      employed in tumor scintigraphy, for its suitability for selective gene induction.
      The plasmid vector pEgr-1-Luc was transfected into AsPc-1 cells and then exposed
      to radioisotopes. Luciferase activity increased by 100-300 times over control. We
      also inserted the herpes thymidine kinase gene (TK) downstream of Egr-1 and
      transfected this construct into AsPc-1 cells. Ga-67-citrate and ganciclovir were
      added to the cells and cell survival was assessed by MTT assay. The growth of
      AsPc-1 cells transfected with the pEgr-TK construct was suppressed 2 days after
      exposure of the cells to Ga-67-citrate. The results indicate that Ga-67-citrate
      may be useful in combining radiation and gene therapies.

PMID- 9143909
TI  - Use of amphotropic retroviral vectors for gene transfer in human colon carcinoma
      cells.
AB  - Previous studies in rodent models have demonstrated the feasibility of gene
      transfer to the stem cells of the intestinal epithelium using ecotropic
      retroviral vectors delivered luminally. This report represents a next step toward
      targeting the human intestine as a site for somatic gene therapy. The first
      experiment assessed the viability of amphotropic retroviral vectors in the
      luminal environment. It was found that after 4 hr at 37 degrees C in luminal
      effluent, the loss of titer was no greater than when incubated in control media.
      Likewise, neither the vector nor the target cells were adversely affected by N
      acetylcysteine, which is likely to be used as a preparatory agent for mucus
      removal. To determine whether human intestinal cells are transducible by these
      vectors, three colon carcinoma cell lines were studied: HT-29, T84, and Caco-2.
      All were transduced; however, the expression of the reporter gene was highest in
      the HT-29 cells. Subsequent studies using these cells showed that with regular
      stocks of vector, gene transfer peaked at a stock dilution of 1/10 and declined
      at full strength. This problem could be partially overcome by centrifugal
      concentration of the retroviral stocks. With this approach, gene transfer
      increased with increasing particles up to 10x regular stock titers but was
      inefficient at 100x. Overall, these findings provide encouraging evidence that
      amphotropic retroviral vectors may eventually be used for in vivo gene transfer
      into human intestinal epithelium. However, they also point to the need for
      improved methods of concentrating retroviral vectors.

PMID- 9143910
TI  - In vitro assembly of SV40 virions and pseudovirions: vector development for gene
      therapy.
AB  - SV40 is an attractive potential vector with high-efficiency gene transfer into a
      wide variety of human tissues, including the bone marrow, a critical target organ
      for the cure of many diseases. In the present study, the three SV40 capsid
      proteins, VP1, VP2, and VP3, were produced in Spodoptera frugiperda (Sf9) insect
      cells. Their co-production led to spontaneous assembly of SV40-like particles.
      Nuclear extracts containing the three proteins were allowed to interact with
      purified SV40 DNA, or with plasmid DNA produced and purified from Escherichia
      coli. The experiments demonstrated a physical association between the DNA and
      capsid proteins, protection from DNase I digestion, and the formation of
      infectious particles. The results indicate that intact, supercoiled DNA is being
      packaged and transmitted into the target cells. The transmitted DNA is
      biologically functional in gene expression and replication. The process, which
      utilizes naked DNA, is not dependent on the SV40 packaging signal ses. The
      procedure allows packaging of plasmids significantly larger than SV40 and permits
      the inclusion of potent regulatory signals, such as beta-globin locus control
      region (LCR) elements. These studies are the first step in the development of
      purified, in vitro-constructed pseudovirions for experimental and medical use.

PMID- 9143911
TI  - Construction and characterization of a recombinant vaccinia virus expressing
      murine intercellular adhesion molecule-1: induction and potentiation of antitumor
      responses.
AB  - The intercellular adhesion molecule-1 (ICAM-1) has been associated with cellular
      migration into inflammatory sites and with facilitating interactions between
      lymphocytes and tumor targets in the pathway of cell-mediated cytotoxicity. More
      recently, ICAM-1 has become increasingly implicated in the costimulation of T
      cell functions, such as antigen-dependent T cell proliferation. Previous murine
      studies have shown that the introduction of the ICAM-1 gene into tumor cells
      using retroviral vectors led to enhanced antitumor responses. In this study, we
      report the construction, characterization, and immunological consequences of a
      recombinant vaccinia virus expressing murine ICAM-1. Vaccinia virus represents an
      attractive vector for the delivery of molecules such as ICAM-1 due to its wide
      host range, rapid infection, and functional expression of inserted gene products.
      The infection of tumor cells with this recombinant virus resulted in the
      expression of functional ICAM-1. Infected tumors provide accessory or secondary
      signals to lymphoblasts in vitro, resulting in enhanced cytokine production or
      alloreactive cytotoxic T lymphocyte (CTL) activity. In vivo, we demonstrated that
      weakly immunogenic syngeneic tumors, infected with and expressing rV-ICAM-1, were
      rejected by immunocompetent hosts. Furthermore, immunization with rV-ICAM-1
      infected tumors resulted in the rejection of subsequent tumor challenge,
      providing evidence for recall response and immunological memory. These studies
      demonstrated the utility of a recombinant vaccinia virus to deliver and
      efficiently express ICAM-1 molecules on tumor cells for potential gene therapy
      and recombinant approaches to cancer immunotherapy.

PMID- 9143912
TI  - Protection of primary human T cells from HIV infection by Trev: a transdominant
      fusion gene.
AB  - Gene therapy is one of several approaches that are being tested in the search for
      an effective anti-human immunodeficiency virus (HIV) treatment. In this strategy,
      a "protective" gene would be introduced into target cells, rendering them
      relatively resistance to the virus-induced cytopathicity. Tat and Rev are viral
      proteins essential for HIV gene expression. Tat increases viral gene
      transcription and Rev is responsible for the nuclear export of mRNA encoding
      structural viral proteins. A fusion protein (Trev) was constructed, joining Tat
      and Rev transdominant mutant gene sequences. Previously, we showed that Trev
      inhibits both Tat and Rev activities in Jurkat T cells. To determine whether Trev
      could inhibit HIV replication in primary cells, we transferred the trev gene to
      peripheral blood lymphocytes and challenged them with different HIV strains.
      Levels of HIV p24 antigen (Ag) were reduced 4- to 15-fold in cultures of Trev
      CD4+ T cells infected with two HIV primary clinical isolates and were not
      detectable in cultures infected with HIV strains NL4-3 and SF2. In contrast,
      cultures of nontransduced CD4+ T cells infected with the same viruses had levels
      of HIV p24 Ag up to 10 ng/ml. Trev-transduced CD4+ T cells demonstrated increased
      survival following HIV challenge for the length of the experiments (30 days). We
      did not observe rapid emergence of Trev-resistant HIV in our cultures. Following
      HIV challenge, cell-associated Trev protein was increased, supporting the
      hypothesis that cells surviving Trev expression provided a cell survival
      advantage. This work showed that Trev was able to inhibit HIV replication in
      primary CD4+ T cells, and, therefore the trev gene could be a candidate for gene
      therapy against HIV.

PMID- 9143913
TI  - Evaluation of recommendations for replication-competent retrovirus testing
      associated with use of retroviral vectors.
AB  - With input from the gene therapy community, CBER is actively examining the
      recommendations for RCR testing during retroviral vector production, production
      of ex vivo-transduced cells, and in patients who receive such material. Our
      initial recommendations were made at a time when our experience with RCR
      detection assays and clinical use of retroviral vectors was limited. As the gene
      therapy field has matured, there is an increasing amount of data available on RCR
      detection assays and from monitoring of patients in clinical trials. The
      cumulative data give assurance that RCR detection assays in use are of sufficient
      sensitivity to provide a margin of safety to patients: no patients to date have
      evidence of RCR infection. However, CBER encourages members of the gene therapy
      community to continue to submit data to the FDA or to publish data that will
      enhance the cumulative data base on RCR testing assays, experience with different
      VPC, and patient monitoring. Based on the analysis of data accumulated to data,
      and ongoing discussions with members of the gene therapy community, CBER is
      proposing to discuss changes to the current RCR testing recommendations, as
      summarized below. RCR testing during production of retroviral vector and ex vivo
      transduced cells. Development of characterized standards for RCR testing of
      supernatant and cells should allow comparison of assay sensitivity. One proposal
      under consideration is to apply statistical methods to determine how much
      material needs to be tested independent of the size of the production lot. Data
      and discussion are still needed to define a limit concentration and a value for
      probability of detection for RCR testing, while maintaining an appropriate margin
      of safety. These modifications of RCR testing strategies could lead to
      improvements in assay sensitivity. Additional discussion and data are also needed
      to evaluate the current recommendations of the testing for ex vivo-transduced
      cells: should both cells and supernatant be tested in all cases? RCR testing
      during patient follow-up. The time points required for RCR testing during patient
      follow-up need examination. One proposal under consideration is to sample and
      assay at three time points during the first year of treatment (e.g., 4-6 weeks, 3
      months, and 1 year post-treatment). Further discussion is needed to define
      appropriate additional follow-up. Choice of assays to detect surrogate markers
      for RCR infection (i.e., serologic or PCR-based assays) should consider mode of
      vector administration and the patient population. Positive results with such
      assays should be pursued by direct culture assay to obtain and characterize the
      infectious viral isolate. These proposals will be the focal point for the
      discussion at the Retroviral Vector Breakout Session at the 1997 FDA/NIH Gene
      Therapy Conference. After the 1997 FDA/NIH Gene Therapy Conference, CBR plans to
      propose revised recommendations for RCR testing for public comment.

PMID- 9143914
TI  - Phase I/IB study of immunization with autologous tumor cells transfected with the
      GM-CSF gene by particle-mediated transfer in patients with melanoma or sarcoma.
AB  - The objective of this Phase I study is to assess the acute and long-term
      toxicities of intradermal vaccination of cancer patients with lethally-irradiated
      tumor cells that have been transfected by particle-mediated gene transfer (PMGT)
      with gold particles coated with human granulocyte-macrophage colony stimulating
      factor (GM-CSF) DNA in a plasmid expression vector. The GM-CSF DNA-coated gold
      particles are delivered to tumor cells using helium pressure with a hand held
      gene delivery device. Preclinical studies have demonstrated that vaccination of
      mice with irradiated, GM-CSF-transfected melanoma cells provided protection from
      subsequent challenges with non-irradiated, non-transfected tumor cells. Ongoing
      human tumor immunotherapy studies use patients' melanoma or renal carcinoma cells
      transfected with a retroviral vector containing GM-CSF cDNA as a vaccine to
      elicit anti-tumor immune responses. PMGT transfection, unlike retroviral
      transfection, does not require tumor cells to proliferate in vitro to undergo
      gene transfer. Instead, tumor tissue can be dissociated into small tissue clumps
      or cell aggregates and then immediately transfected using the gene gun. PMGT
      physically inserts the DNA without the need for cell surface interaction with
      viral components or exposure of the patient to viral antigens. As described in
      this protocol, fresh human sarcoma and melanoma specimens can be transfected with
      the GM-CSF DNA-coated gold particles with subsequent production of biologically
      active GM-CSF protein. In this study tumor tissue will be obtained from patients
      with melanoma or sarcoma. Tumor tissue will be dissociated, irradiated, and
      transfected with GM-CSF DNA by PMGT. In this ascending dosage study, two dose
      levels of GM-CSF DNA will be studied in 2 groups of 6 patients each. Patients
      will receive two intradermal injections of the irradiated, transfected tumor in a
      single extremity. On days 3 and 14 post-vaccination, patients will undergo
      surgical excision of the vaccination sites to assess GM-CSF production and
      infiltration of immune effector cells. On Day 25, patients will undergo DTH
      testing with intradermal injection in their opposite extremity of 5 x 10(6)
      irradiated non-transfected autologous tumor cells cryopreserved at the time of
      vaccine preparation. This injection site will be assessed on day 28 post
      vaccination and surgical excision of the DTH testing site will be performed on
      day 28 if a positive reaction is noted. The patients will be observed for local
      and systemic toxicity on days 2, 3, 5, 8, 14, 25, and 28 after the vaccination.
      Restaging of the patients' disease and long term toxicity evaluation will be
      performed at 3, 6, and 12 months and then yearly.

PMID- 9143915
TI  - Seven novel mutations in carbonic anhydrase II deficiency syndrome identified by
      SSCP and direct sequencing analysis.

PMID- 9143916
TI  - Mutations in SRY and SOX9: testis-determining genes.

PMID- 9143917
TI  - Identification of novel missense mutations in the Norrie disease gene associated
      with one X-linked and four sporadic cases of familial exudative
      vitreoretinopathy.
AB  - X-linked Familial Exudative Vitreoretinopathy (XLFEVR) is a hereditary eye
      disorder that affects both the retina and the vitreous body. It is characterized
      by an abnormal vascularization of the peripheral retina. It has been previously
      shown by linkage and candidate gene analysis that XLFEVR and Norrie disease are
      allelic. In this report we describe four novel mutations (R41K, H42R, K58N, and
      Y120C) in the Norrie disease gene associated with one X-linked and four sporadic
      cases of FEVR. One mutation (H42R) was found to be segregating with the disease
      in three generations (X-linked family), and the others are sporadic. These
      sequence alterations changed the encoded amino acids in the Norrie disease
      protein and were not found in 17 unaffected family members or in 36 randomly
      selected normal individuals. This study provides additional evidence that
      mutations in the same gene can result in FEVR and Norrie disease. It also
      demonstrates that it may be beneficial for clinical diagnosis to screen for
      mutations in the Norrie disease gene in sporadic FEVR cases.

PMID- 9143918
TI  - Norrie disease gene mutation in a large Costa Rican kindred with a novel
      phenotype including venous insufficiency.
AB  - A large Costa Rican kindred has been identified with 15 males affected with
      congenital blindness, progressive bearing loss, and venous insufficiency. Due to
      ophthalmological and audio-otological findings, including bilateral retinal
      dysplasia and detachment, progressive bilateral sensorineural hearing loss, and
      an X-linked pattern of inheritance, a tentative diagnosis of Norrie disease was
      considered. However, venous insufficiency is a clinical finding not reportedly
      associated with Norrie disease. Genetic linkage analysis using microsatellite
      repeat markers demonstrated linkage to Xp11.23-11.4 (z = 2.723 at theta = 0.0). A
      candidate gene approach using the Norrie disease gene (NDP), which maps to
      Xp11.3, revealed a point mutation in the third exon resulting in substitution of
      phenylalanine for leucine at position 61. The precise function of the gene
      product, norrin, has yet to be elucidated; however, it has been postulated to be
      involved in the regulation of neural cell differentiation and proliferation,
      although hypotheses have been considered for its role in vascular development in
      the eye. The finding of a mutation in NDP in association with peripheral vascular
      disease may provide valuable insight into the potential role of this gene in
      cellular processes.

PMID- 9143919
TI  - Ornithine transcarbamylase deficiency: ten new mutations and high proportion of
      de novo mutations in heterozygous females.

PMID- 9143920
TI  - Tissue distribution of the ND4/11778 mutation in heteroplasmic lineages with
      Leber hereditary optic neuropathy.
AB  - Leber hereditary optic neuropathy (LHON) is a maternally inherited eye disease
      most commonly caused by mitochondrial DNA (mtDNA) point mutation at position
      11778, 3460, or 14484. Approximately 14% of families show heteroplasmy for the
      pathogenic mutations but little is known about the mutational burden in different
      tissues of these heteroplasmic individuals. Consequently, estimating the risks of
      visual loss is difficult. This study presents quantitative mutation analyses of
      tissues representing all embryonal layers in two families heteroplasmic for the
      11778 mutation. These analyses show that a high amount of mutated mtDNA in
      leukocytes is correlated with a high proportion of mutated mtDNA in other
      tissues.

PMID- 9143921
TI  - Mutation pattern in the Bruton's tyrosine kinase gene in 26 unrelated patients
      with X-linked agammaglobulinemia.
AB  - Mutation pattern was characterized in the Bruton's tyrosine kinase gene (BTK) in
      26 patients with X-linked agammaglobulinemia, the first described immunoglobulin
      deficiency, and was related to BTK expression. A total of 24 different mutations
      were identified. Most BTK mutations were found to result in premature termination
      of the translation product. Mutations were detected in most BTK exons with a
      predominance of frameshift and nonsense mutations in the 5' end of the gene and
      missense mutations in its 3' part, corresponding to the catalytic domain of the
      enzyme. Nonsense and frameshift mutations were associated with diminished levels
      of BTK mRNA expression, except for a frameshift mutation in exon 17 and two
      nonsense mutations in exon 2, indicating that these cases are not confined to
      penultimate exons. One amino acid substitution (R28H) was found in the pleckstrin
      homology domain's residue, which is mutated in mice bearing the X-linked
      immunodeficiency phenotype; another substitution (R307G) was identified in the
      src homology domain 2. All remaining amino acid substitutions were found in the
      catalytic domain of Btk.

PMID- 9143922
TI  - Analysis of the myoglobin gene in heart disease.
AB  - Analysis of the myoglobin gene from a large number of patients with cardiac
      disease disclosed a single substantive mutation. However, no evidence of
      biochemical or physiological dysfunction due to this mutation was detected. We
      conclude that, within the limits of presently available techniques, myoglobin
      mutations are unlikely to contribute substantially to the genotypic background of
      cardiac disease in the general population.

PMID- 9143923
TI  - (G586V) substitutions in the alpha 1 and alpha 2 chains of collagen I: effect of
      alpha-chain stoichiometry on the phenotype of osteogenesis imperfecta?
AB  - Osteogenesis imperfecta (OI) is a congenital disease of connective tissue, most
      often caused by single amino acid substitutions of glycine residues within the
      triple helical region of collagen I. Collagen I consists of two alpha 1 chains
      and one alpha 2 chain. Thus, a substitution in the alpha 1(I) chain is thought to
      affect the function of the collagen molecule more than would a similar
      substitution in the alpha 2(I) chain, thereby causing more severe OI.
      Theoretically this hypothesis may be tested by comparing patients with identical
      substitutions in different alpha-chains. We present a Gly586Val substitution in
      the alpha 1(I) chain, and compare our findings to those resulting from Gly586Val
      substitutions in the alpha 2(I) chain (Forlino et al., 1994; Bateman et al.,
      1991). Our proband had lethal OI type II. Most alpha-chains of collagen I
      produced by his cultured fibroblasts were overmodified. The denaturation
      temperature of the abnormal collagen was 1.5 degrees C below normal. Cyanogen
      bromide cleavage and subsequent sequencing revealed a G-to-T base substitution at
      nucleotide 2420 of COL1A1, resulting in a Gly586Val substitution. The collagen
      findings were almost identical to those reported by Bateman et al. (1991) and
      Forlino et al. (1994), but the clinical phenotypes were different: the patients
      with the alpha 2(I) substitutions had OI type IV and III and not the lethal OI
      type II of our proband. It is known that identical biochemical aberrations in the
      same chain may have different phenotypic effects, both within families and
      between non-related patients. This must be taken into account in our cautious
      proposal that substitutions in the alpha 1(I) chain may have more serious
      consequences than similar substitutions in the alpha 2(I) chain.

PMID- 9143924
TI  - Two mutations in the same low-density lipoprotein receptor allele act in synergy
      to reduce receptor function in heterozygous familial hypercholesterolemia.
AB  - Mutations in genes are not necessarily pathogenic. Expression of mutant genes in
      cells can therefore be required to demonstrate that mutations in fact disturb
      protein function. This applies especially to missense mutations, which cause an
      amino acid to be replaced by another amino acid. In the present study of two
      families with familial hypercholesterolemia in the heterozygous form, we found
      two mutations in the same allele of the low-density lipoprotein (LDL) receptor
      gene: a missense Asn543. His mutation (N543H) in exon 11, and an in-frame 9-bp
      deletion (2393del9) in exon 17. The two mutations were identified in heterozygous
      FH index patients in whom no other pathogenic mutations were detected by SSCP
      analysis of the remaining 16 exons and the promoter region. Both mutations
      cosegregated with hypercholesterolemia within the families. Each of these
      mutations had little or no effect on receptor function in transfected COS cells,
      but when both mutations were present simultaneously, receptor function, as
      assessed by flow cytometric measurement of fluorescent LDL uptake in cells, was
      reduced by 75%. Immunostainable receptors on the cell surface were decreased by
      80% as measured by flow cytometry. The two mutations therefore acted in synergy
      to affect receptor function, possibly during intracellular receptor transport,
      since Northern blot analysis suggested that mRNA levels were unaffected. Without
      screening of the entire coding regions of the gene, the synergistic action of
      these two LDL receptor mutations would not have been detected.

PMID- 9143925
TI  - Similar mutant frequencies observed between pairs of monozygotic twins.
AB  - The relative contribution of both genetic and environmental factors to
      spontaneous mutation frequency in humans is unknown. We have investigated the
      contribution of genetic factors to this phenomenon by determining the in vivo
      mutant frequency at the hypoxanthine-guanine phosphoribosyltransferase (hprt)
      locus in circulating T-lymphocytes obtained from pairs of monozygotic twins. hprt
      mutant frequencies were determined three times over fourteen days in six sets of
      monozygotic male twins (mean age 30) taking part in a Russian Space Program
      inclined bed rest experiment. Blood samples were obtained prior to, during, and
      immediately following the experiment. Mononuclear cells were separated, frozen,
      and flown to Canada for analysis using the hprt T-lymphocyte clonal assay. There
      is no evidence within this data set to demonstrate that the period of inclined
      bed rest to simulate the effects of weightlessness had any effect on the observed
      mutant frequency. However, the average mutant frequency for the six sets of
      Russian twins was found to be three times higher than that of Western
      counterparts. More surprisingly, the spontaneous mutant frequency of monozygotic
      twins was found to be much more similar within pairs than between pairs of twins.
      These data suggest that the contribution of genetics in the determination of
      mutation frequency is substantial. However, whether high concordance within twin
      pairs reflects shared environmental experience as well as common genetic factors
      is not entirely clear. More data will be required to distinguish genetic from
      environmental factors and to determine the degree to which mutant frequency is
      genetically determined.

PMID- 9143926
TI  - Example of somatic mosaicism in a series of de novo neurofibromatosis type 1
      cases due to a maternally derived deletion.
AB  - Neurofibromatosis type 1 (NF1), affecting primarily the growth of neural crest
      derived tissues, is one of the most common autosomal dominant genetic disorders
      with an unusually high spontaneous mutation rate. In four cases of sporadic NF1,
      demonstrated by hemizygosity to have a deletion involving the NF1 gene, we were
      able to assign the deletion event to the maternally derived chromosome. One of
      these individuals was determined to be a somatic mosaic for NF1, as a trace of
      the maternally derived haplotype was detected at the NF1 locus. This indicated a
      postzygotic, as opposed to gametic, deletion event. It may be that somatic
      mosaicism is more common in NF1 than has hitherto been appreciated and may be
      responsible in part for the high mutation rate in this disorder. In addition, it
      is suggested that the mechanism(s) of gene deletion is subject to a parent of
      origin effect, being more frequent on the maternally derived chromosome. This is
      in contrast to the other types of mutations which, in sporadic NF1, have been
      found to occur preferentially on the paternally derived chromosome.

PMID- 9143927
TI  - Deletions spanning the neurofibromatosis type 1 gene: implications for genotype
      phenotype correlations in neurofibromatosis type 1?
AB  - Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder characterized by
      abnormalities of tissues predominantly derived from the neural crest. Symptoms
      are highly variable and severity cannot be predicted, even within families. DNA
      of 84 unrelated patients with NF1, unselected for clinical features or severity,
      were screened with intragenic polymorphic repeat markers and by Southern analysis
      with cDNA probes. Deletions of the entire gene were detected in five patients
      from four unrelated families. Their phenotype resembled that of five previously
      reported patients with deletions, including intellectual impairment and
      dysmorphic features, but without an excessive number of dermal neurofibromas.
      This report supports the hypothesis that large deletions spanning the entire NF1
      gene may lead to a specific phenotype.

PMID- 9143928
TI  - Scanning method to identify the molecular heterogeneity of delta-globin gene
      especially in delta-thalassemias: detection of three novel substitutions in the
      promoter region of the gene.
AB  - A scanning strategy for the detection of delta-globin gene mutations and
      polymorphisms is presented. This procedure is based on the denaturing gradient
      gel electrophoresis (DGGE) of four different artificially amplified DNA fragments
      which cover the promoter, the exons, as well as IVS I of the reported gene. To
      estimate the efficiency and sensitivity of the proposed procedure, we analysed
      the appropriate controls of delta-thalassemic carriers, uncharacterised delta
      thalassemias and cases with normal hematological phenotype, but slightly
      increased (up to 3.5%) HbA2. DGGE results permitted the identification of delta
      globin gene mutations and the polymorphism -199 (T-->C). Three novel base
      substitutions inside the promoter region of the gene [-65 (A-->G), -55 (T-->C), 
      36 (C-->A)], were also revealed. These changes are either linked in cis with
      other mutations or are responsible for thalassemias or for positive regulatory
      effect in delta-globin gene expression. The proposed experimental strategy
      consists of an accurate, rapid, safe and inexpensive screening procedure for
      establishing the molecular basis of delta-globin gene defects, suitable for the
      application for both research and diagnostics.

PMID- 9143929
TI  - A five-basepair deletion (7118 delTTTTA) identified within neurofibromatosis
      (NF1) exon 39.

PMID- 9143930
TI  - Three novel point mutations in the dystrophin gene in DMD patients.

PMID- 9143931
TI  - New nonsense mutation in the breast cancer-1 gene in a French site-specific
      breast cancer family.

PMID- 9143932
TI  - Recurrent COL3A1 mutation results in EDS IV or familial aneurysms.

PMID- 9143933
TI  - A new missense mutation in exon 6 of the proteolipid protein gene in a patient
      with Pelizaeus-Merzbacher disease.

PMID- 9143934
TI  - Identification of a novel somatic mutation in the RET proto-oncogene in a patient
      with sporadic medullary thyroid carcinoma.

PMID- 9143935
TI  - Class II MHC expression on rat intestinal intraepithelial lymphocytes.
AB  - The expression of class II major histocompatibility complex (MHC) on rat
      intestinal intraepithelial lymphocytes (IELs) and mesenteric lymph node cells
      (MLNCs) were examined by immunofluorescence and flow cytometry. As expected,
      MLNCs contain eight small populations of CD4+ class II MHC+ T-cells in addition
      to classical antigen presenting cells. In contrast, rat IELs include a
      significant population of class II MHC+ T-cells, predominantly in the CD8+ CD4
      alpha beta TCR+ subset. IEL samples with a relatively high percentage of class II
      MHC+ cells also include some CD4+ class II MHC+ cells; IEL samples with a low
      percentage of class II MHC+ cells also include some CD4- CD8- class II MHC+
      cells. The role of lymphocyte subpopulations in the intestinal epithelium may
      need to be revisited in consideration of these findings.

PMID- 9143936
TI  - Extracellular adenosine 5' triphosphate involvement in the death of LAK-engaged
      human tumor cells via P2X-receptor activation.
AB  - This study reports that extracellular ATP is a critical factor involved in LAK
      cell-mediated cytotoxicity. Human colon carcinoma LoVo cells were resistant to
      LAK cells as well as to ATP, while their multidrug resistant (MDR-1+) derivative,
      LoVo-Dx cells, were sensitive to both LAK and ATP. LoVo-Dx cells, became
      resistant to LAK cells and ATP after 48 h pretreatment with Phorbol 12-Myristate
      13-Acetate (PMA), while 48 h pretreatment with verapamil in parallel sensitized
      LoVo cells to LAK cells and to ATP as well. The sensitivity to ATP and LAK cells
      was not related to the expression of extracellular ecto-ATPase activity on cell
      targets membranes. Conversely, apyrase, an enzyme with powerful ecto-ATPase
      activity, abolished the LAK- and ATP-mediated cytotoxicity. Furthermore, ADP-beta
      S, an antagonist of ATP, abolished both LAK and ATP-mediated cell killing. Purine
      binding sites have been detected by radioreceptor assays with ADP-beta[35S] on
      the cell surface of ATP and LAK-sensitive LoVo-Dx cells. By contrast, no
      nucleotide receptor was found on the ATP and LAK-resistant cells. Such a putative
      cytotoxic purinoreceptor has been categorized as P2x purinergic receptor by a
      panel of synthetic nucleotides. These results demonstrate that extracellular ATP
      is needed for an efficient LAK cell-mediated killing of tumor cells. We propose
      that ATP acts as a natural amplifier of physical, or immune cytotoxic damages
      since it may be released in large amounts from target cells injured by several
      cytotoxic mediators secreted by LAK effectors.

PMID- 9143937
TI  - Clinically insignificant (natural) autoantibodies against acetyl cholinesterase
      in the sera of patients with a variety of neurologic, muscular and autoimmune
      diseases.
AB  - Acetyl cholinesterase (AChE) antibodies were shown to be associated with
      myasthenia-like neuromuscular disease. However, it is not clear whether they
      cause the disease, or their presence is secondary to the disease or an unrelated
      epiphenomenon. Therefore, AChE antibodies were studied in the sera of 135
      patients with neurologic, muscular and autoimmune diseases, using enzyme linked
      immunosorbent assay (ELISA), immunoblotting and enzyme inhibition assay. In 12
      sera the AChE binding by ELISA was greater than 2 standard deviations (SDs) above
      the mean value of the 20 healthy controls. However, this increased binding was
      not disease-specific, had no clinical correlates and could not be demonstrated
      using Western blotting and AChE enzyme inhibition assay, suggesting that these
      antibodies are naturally occurring, pathogenically unimportant autoantibodies.
      The finding also supports a possible pathogenic role for the previously reported,
      high titer, high affinity, inhibitory AChE antibodies in the neuromuscular
      disease.

PMID- 9143938
TI  - V beta 8+CD4-CD8- subpopulation induced by staphylococcal enterotoxin B.
AB  - Injection of staphylococcal enterotoxin B (SEB) into BALB/c mice induced the
      depletion of V beta 8+ T-cells which were either V beta 8+CD4+ or V beta 8+CD8+
      cells. The CD8 molecule on V beta 8+CD8+ cells was found to decrease at 72 h
      after SEB treatment while the V beta 8 molecule on V beta 8+ cells or CD4
      molecule on V beta 8+CD4+ cells was not affected. Furthermore, a subpopulation of
      V beta 8+CD4-CD8- T-cells was also induced after SEB-priming. This subpopulation
      can be found in spleen or lymph nodes. It was small in size and constituted the
      major part of V beta 8+ cells in lymph nodes at 72 h after SEB-priming. Some of
      the V beta 8+CD4-CD8- T-cells might be autoreactive because they could be
      stimulated to proliferative by syngenic mitomycin C-treated splenocytes.

PMID- 9143939
TI  - A polypeptide encoded within the murine AIDS defective virus stimulates primary
      proliferation of CD8+ T-cells.
AB  - The murine AIDS (MAIDS) is a retrovirus-induced disease that shows severe
      immunodeficiency with abnormal lymphoproliferation in susceptible strains of
      mice. To clarify the antigenicity of gag gene products of the LP-BM5 defective
      virus, which is known as the causative virus of MAIDS, we expressed and purified
      the gag p12 gene product (P12) by using a baculovirus expression vector system.
      The P12 protein strongly stimulated the proliferation of normal C57BL/6 (B6)
      lymph node T-cells in vitro. Furthermore, a 25-mer synthetic polypeptide within
      the P12 sequence gave rise to the similar or even higher activation of T-cells.
      The phenotype of responding T-cells was found to be CD8+ CD44low, indicating that
      naive CD8+ T-cells respond against a peptide encoded within a MAIDS defective
      virus gag p12 gene. Finally, the expression of T-cell receptor (TcR) V beta on
      the responding CD8+ T-cells was analyzed. Although CD8+ T-cells with the
      particular V beta chains were expanded in response to the 25-mer peptide, this
      polypeptide does not seem to be a superantigen, since this response is MHC class
      I-restricted and the V beta preference is not striking. The presentation pathway
      of this highly antigenic polypeptide will be discussed.

PMID- 9143940
TI  - CD70 expression on T-cell subpopulations: study of normal individuals and
      patients with chronic immune activation.
AB  - CD70, the ligand of CD27, is a member of the TNF family, which includes molecules
      essential in the regulation of lymphocyte growth and survival. It is absent on
      resting lymphocytes but can be induced in vitro with activating stimuli. To
      extend information about its expression by different T-cell subpopulations, and
      its regulation in normal and pathologic conditions, highly purified T-cell
      subpopulations were studied: CD70 expression depended both on the activating
      stimulus and on the T-cell subset analyzed. PMA + Ionomycin induced CD70 on the
      large majority of CD8+ cells, but only on a minority of CD4+ cells (P < 0.002),
      and among these, preferentially on the CD45R0+ subset compared with the CD45RA+.
      The presence of CD4+ lymphocytes in cell cultures containing mixtures of T-cell
      subsets inhibited CD70 expression on CD8+ cells. On the contrary, stimulation
      with allogeneic cells induced CD70 expression also on CD4+ cells. Moreover, CD70
      was found to be expressed by chronically in vivo activated T-cells, in conditions
      characterized by allogeneic and autoimmune reactions. These data suggest a
      possible role of CD70 in the pathogenesis of immune dysregulation; interestingly,
      this role may not be simply restricted to bind to, and signal through, CD27,
      since cross-linking of CD70 enhances the proliferative response induced by the
      stimuli used to elicit its expression.

PMID- 9143941
TI  - Expression of NRAMP1 molecule in human peripheral blood leukocytes.
AB  - Natural resistance or susceptibility of host to infection with several
      intracellular pathogens, such as Mycobacterium, Salmonella and Leishmania, is
      controlled in mice by the expression of a single dominant gene locus designated
      Lsh/Ity/Bcg. Natural resistance-associated macrophage protein gene 1 (Nramp1) was
      isolated as a candidate gene. Nramp1 gene encodes a 60 kDa polypeptide with 10-12
      potential transmembrane domains and an evolutionary conserved consensus transport
      motif. The present study shows that the human NRAMP1 gene is expressed in all
      established hematopoietic cell lines examined, including monocytes/macrophages
      and B- and T-lymphocytes. In contrast, cell type-specific expressions are
      observed in human peripheral blood leukocytes. NRAMP1 expression is very low
      level in granulocytes. B- and T-lymphocytes are equivalent in the level of NRAMP1
      expression. Notable expression of NRAMP1 gene can be detected in the monocyte
      population. These results have important implications for the host defence
      mechanisms and the pathogenesis of intracellular pathogens which are recognized
      and ingested by the mononuclear phagocyte system including monocytes/macrophages.

PMID- 9143943
TI  - Effects of crude antigenic fractions of Leishmania major on natural killer cell
      cytotoxicity, interferon-gamma and interleukin-4 secretion from peripheric blood
      lymphocytes of unexposed individuals.
AB  - The crude antigenic fraction (CAF) isolated from Leishmania major was
      fractionated into three subfractions by sodium dodecyl sulphate-polyacrylamide
      gel (SDS-PAGE). The effects of CAF and its subfractions on NK cell cytotoxicity
      is investigated by chromium release assay. These subfractions designated as
      fractions 1, 2 and 3 correspond to 97.4-66 kD, 66-45 kD and 29 kD and below
      respectively. Although both CAF and its subfractions have inhibited the
      cytotoxicity of natural killer (NK) cells, the effects of fractions 2 and 3 were
      more pronounced. The effect of the fractions on the Interferon-gamma (IFN-gamma)
      and Interleukin-4 (IL-4) secretion by peripheric blood lymphocytes was also
      analyzed. It was found that CAF and fraction 1 induce IFN-gamma secretion while
      on the other hand IL-4 secretion was mostly suppressed by fraction 2. Therefore,
      further research is being executed which focuses on the effects of CAF, fractions
      1 and 2 on macrophage effector functions.

PMID- 9143942
TI  - HIV-1 recombinant gp41 induces IL-10 expression and production in peripheral
      blood monocytes but not in T-lymphocytes.
AB  - The effects of recombinant gp41 (rgp41) protein of the human immunodeficiency
      virus type 1 (HIV-1) on interleukin 10 (IL-10) expression and production using
      human peripheral blood mononuclear cells was investigated. Expression of IL-10
      mRNA was demonstrated within 3 h of cell exposure to endotoxin-free rgp41 by RT
      PCR and Northern blot analyses in a time- and dose-dependent manner. IL-10
      protein was detected in the supernatants of peripheral blood mononuclear cells
      following stimulation with rgp41 also in a dose dependent manner. Fractionation
      of peripheral blood mononuclear cells showed that purified monocytes but not
      purified T-lymphocytes induced expression of IL-10 mRNA by rgp41. Recombinant HIV
      1 gp120 exhibits similar influences on the induction of IL-10. These results
      indicate that both of these components of envelope proteins may play an important
      role in HIV related immunomodulation by influencing regulatory functions of
      monocytes and macrophages.

PMID- 9143944
TI  - Structural constraints of HIV-1 Nef may curtail escape from HLA-B7-restricted CTL
      recognition.

PMID- 9143945
TI  - Baseline HIV type 1 load predicts the long-term clinical outcome of infected
      patients. The 'positive feedback theory'.

PMID- 9143946
TI  - Pathophysiologic alterations in shoulder injury.

PMID- 9143947
TI  - Proximal humeral replacement for complex fractures: indications and surgical
      technique.

PMID- 9143948
TI  - Complications of humeral head replacement for proximal humeral fractures.
AB  - The indications for humeral head replacement in acute fractures and in chronic
      fracture problems have been studied over many decades and are reasonably well
      defined. Complications have probably been understudied. Many different
      complications occur, and their frequency and the need for reoperation is quite
      high. Because of the variety of complications that occur, familiarity with
      preventive measures and treatment options is important, not only to deal with
      complications arising from endoprostheses, but also to treat musculoskeletal
      infections, nerve injuries, fractures, instability, nonunion of tuberosities,
      malunion, and rotator cuff or capsule contracture or tearing. Physicians also
      must be able to integrate reparative/reconstructive surgery with a program of
      postoperative rehabilitation. The challenges are many. Treatment often provides
      considerable improvement for the patient, but often the extent of the improvement
      is somewhat less than optimal.

PMID- 9143949
TI  - Complications of internal fixation of proximal humeral fractures.

PMID- 9143950
TI  - Normal shoulder mechanics and function.

PMID- 9143951
TI  - Shoulder rehabilitation: clinical application, evaluation, and rehabilitation
      protocols.
AB  - This chapter has discussed and illustrated a shoulder rehabilitation protocol
      based on restoration of the anatomy, biomechanics, physiology, and motor firing
      organization that is responsible for normal shoulder function. Many protocols
      exist in the literature, most of which appear to achieve good results. There are
      no outcomes data to suggest the most efficacious protocols. Adherence to the
      basic principles outlined in these chapters appears to allow the best framework
      for constructing a good program.

PMID- 9143952
TI  - Current research on muscle activity about the shoulder.

PMID- 9143953
TI  - Simulators of hand infections.

PMID- 9143954
TI  - Longitudinal failure of upper-limb formation.

PMID- 9143955
TI  - The management of acute spinal trauma: prehospital and in-hospital emergency
      care.

PMID- 9143956
TI  - Minimally invasive approaches to the spine.

PMID- 9143957
TI  - Minimally invasive arthroscopic spinal surgery.

PMID- 9143958
TI  - Wound complications in total knee arthroplasty.
AB  - Wound problems are a dreaded complication following TKA and the ideal is to avoid
      them. Preventive measures include proper choice of the skin incision, gentle
      handling of the soft tissues, meticulous hemostasis, and wound closure without
      excessive tension. Should persistent wound drainage or soft-tissue necrosis
      occur, early intervention is imperative, because delay risks deep infection and
      failure of the TKA. Cases associated with full-thickness soft-tissue necrosis
      often require transfer of well-vascularized tissue, such as a medial
      gastrocnemius myocutaneous flap reconstruction.

PMID- 9143959
TI  - Extensor mechanism problems in total knee arthroplasty.

PMID- 9143960
TI  - Neurovascular complications following total knee replacement: causes, treatment,
      and prevention.

PMID- 9143961
TI  - Thromboembolic disease.

PMID- 9143962
TI  - The stiff total knee replacement: causes, treatment, and prevention.

PMID- 9143963
TI  - Supracondylar fracture of the distal femur proximal to a total knee replacement.

PMID- 9143964
TI  - Polyethylene wear and osteolysis following total knee replacement.

PMID- 9143965
TI  - Management of the patient with an infected knee arthroplasty.

PMID- 9143966
TI  - Surgical exposure in revision total knee arthroplasty.
AB  - Extensile exposure is one of the crucial skills for managing the challenges
      presented by revision total knee arthroplasty. Full exposure is necessary to
      perform the intricate bone and ligament work, and short incisions combined with a
      timid approach to the quadriceps mechanism will result in inadequate
      reconstruction of the knee. Repair and reconstruction of the facial,
      subcutaneous, and cutaneous tissues to achieve closure are separate and equally
      important skills.

PMID- 9143967
TI  - The management of bone defects in revision total knee arthroplasty.
AB  - The number of failed total knees with large bone defects is increasing. This is
      related to the large number of total knee arthroplasty procedures that are being
      performed in an increasingly active patient population. Long-term results are
      needed to compare clinical outcome and survivorship of allograft reconstruction
      versus custom prosthetic components. A benefit to using allograft reconstruction
      is that the bone deficiency is not increased as occurs with custom devices, and
      may be decreased with incorporation of the graft. In our current economic climate
      there are advantages to using allografts, despite costs as high as $1,600 for
      processing of a proximal or distal femur. In comparison, custom prostheses are
      not as cost effective. A material that can unite and gradually incorporate with
      host bone increases the potential for long-term success. Allograft may be used as
      part of a reconstructive armamentarium for total knee arthroplasty. Allografts
      are not implants and must be used as physiologic material. The early results are
      comparable or superior to traditional methods of reconstruction. The augmented
      bone stock in allograft knees remains a theoretical advantage and may facilitate
      subsequent revisions.

PMID- 9143968
TI  - Cost effectiveness of revision total knee replacement.

PMID- 9143970
TI  - Reflex sympathetic dystrophy, patella infera contracture syndrome, and loss of
      motion following anterior cruciate ligament surgery.

PMID- 9143969
TI  - Patella infera syndrome: an analysis of the patellar tendon pathology.

PMID- 9143971
TI  - Reflex sympathetic dystrophy and pain dysfunction in the lower extremity.

PMID- 9143972
TI  - Technical considerations in the surgical management of tibial fractures.
AB  - The surgical treatment of tibial shaft fractures is generally successful.
      However, significant controversy exists regarding the indications for specific
      types of fixation and the techniques used to apply them. Advances to meet the
      technical challenges of tibial fracture fixation continue to be made, and
      orthopaedic surgeons should have these new techniques at their disposal for
      application to each individual patient's injury.

PMID- 9143973
TI  - Delayed union and nonunion of tibial shaft fractures.

PMID- 9143974
TI  - Open fractures of the tibial shaft.

PMID- 9143975
TI  - Compartment syndrome associated with tibial fracture.

PMID- 9143976
TI  - Fractures of the ankle and the distal part of the tibia.

PMID- 9143977
TI  - Complex fractures of the talus.
AB  - Injuries of the talus make up a significant proportion of complex foot and ankle
      injuries. The severity of these injuries is increasing because the availability
      and use of better safety equipment has allowed more people to survive serious
      accidents. Early rigid and accurate anatomic fixation lead to the best possible
      outcome for each category of talar injury. If osteonecrosis is suspected,
      titanium screws should be used for fixation to allow better postoperative follow
      up. Treatment of osteonecrosis of the talus still depends mainly on clinical
      judgment, with the MRI providing more clinical data. The outcome of the
      osteonecrotic talus has not been established at this point. The approach to the
      talus depends on the judgment and skill of the surgeon; two approaches usually
      are indicated for more severe injuries. A CT scan is quite helpful for fractures
      of the talar body; preoperative planning and the judicious use of malleolar
      osteotomy with preservation of the deltoid artery are advocated. Tibiotalar and
      talocalcaneal motion have been altered as a result of talar fractures. Arthrosis
      of the subtalar joint depends on the degree of injury.

PMID- 9143978
TI  - Salvage procedures for calcaneus fractures.
AB  - Salvage procedures reverse the anatomic factors that cause widening and
      mechanical misalignment of the hindfoot. Posttraumatic arthrosis of the subtalar
      joint is treated by arthrodesis, using techniques that improve alignment. The
      easily measured goal is to restore the normal plantar alignment of the talus
      (Meary's line) and return the calcaneal tuberosity to the weightbearing line
      beneath the talus. The subtalar joint is the joint most often treated by
      arthrodesis, although a triple arthrodesis is sometimes required when Chopart's
      joint is involved.

PMID- 9143979
TI  - Technical factors in hindfoot arthrodesis.

PMID- 9143980
TI  - Hallux valgus.

PMID- 9143981
TI  - Adult acquired flatfoot deformity: treatment of dysfunction of the posterior
      tibial tendon.

PMID- 9143982
TI  - Geriatrics for orthopaedists.
AB  - The care of older patients is challenging and fraught with pitfalls, but the
      orthopaedic surgeon has the opportunity to give the elderly patient a gift that
      is of the highest value at that time of life, the chance to function better and
      more independently. By avoiding hospital-induced problems detecting and managing
      risk factors, and optimizing physical functioning, orthopaedists make major
      contributions to elders' lives.

PMID- 9143983
TI  - Orthopaedic challenges in an aging population.

PMID- 9143984
TI  - Orthopaedic challenges in the aging population: trauma treatment and related
      clinical issues.

PMID- 9143985
TI  - Biomechanical considerations of hip and spine fractures in osteoporotic bone.
AB  - Falls and fall-related hip fractures are among the most serious, common, and
      costly medical problems facing the elderly. Recently, we and others have shown
      that falls to the side, particularly those that end with impact on the hip, raise
      the risk of hip fracture from six- to thirty-fold, compared to about threefold
      increases in risk associated with one SD reduction in BMD at the hip. And yet,
      despite the apparently crucial importance of sideways falls, little is known
      about the mechanics of falling to the side. In addition, while previous studies
      have helped identify those factors that place the elderly at high risk for
      falling and provided assessment procedures that can be used to identify those at
      risk for falls, as far as we are aware no previous work has successfully
      identified subjects at increased risk of falling to the side. Moreover, while
      rigorous, multifactorial fall prevention efforts have demonstrated moderate
      reductions in fall incidence, such programs are expensive and potentially
      inefficient in that they have not consistently demonstrated reductions in the
      numbers of injurious falls. While trochanteric padding systems show considerable
      promise for hip fracture prevention by reducing impact force, they involve
      difficult acceptance and compliance issues and will require large and rigorous
      clinical trials to demonstrate effectiveness. Finally, while it also appears that
      osteodynamic agents can be used to increase BMD at the hip and spine, little is
      known about the local structural consequences of these changes and, in
      particular, if they are sufficient to prevent hip fracture from a severe fall.
      The findings reviewed here thus emphasize the continuing need for combined
      intervention strategies that focus on fall prevention, on reductions in fall
      severity, and on maintaining or increasing bone mass and strength, either through
      targeted exercise programs or the use of osteodynamic agents. By developing and
      refining the factor of risk phi, a property that captures both the contributions
      of bone density and the confounding influences of body habitus and fall severity,
      we believe these intervention strategies can be targeted more appropriately.
      Based on such approaches and an improved understanding of the complex interplay
      between fall biomechanics and bone fragility in the etiology of hip fracture,
      there is hope that the growing worldwide epidemic of hip fractures among the
      elderly can be substantially abated.

PMID- 9143986
TI  - Outcome assessment after fracture in the elderly.

PMID- 9143987
TI  - Osteoporosis: diagnosis and treatment.

PMID- 9143988
TI  - Maintaining and restoring mobility in middle and old age: the importance of the
      soft tissues.
AB  - For many older individuals, impairment of musculoskeletal function, especially
      weakness, stiffness, and pain, cause progressive disability, thereby limiting
      mobility and decreasing the quality of life. With advancing age, musculoskeletal
      soft tissue function declines, susceptibility to degenerative diseases and
      injuries increases, and the ability to recover from disease or injury declines;
      these changes increase the probability of impairment (Fig. 1). However, the
      function of individual cells, tissues, or organ systems may remain stable or even
      improve temporarily with age, and a number of interventions have the potential to
      maintain or improve musculoskeletal function. Age-related changes in cells,
      tissues, and musculoskeletal function are not necessarily unidirectional or
      uniform among individuals, organ systems, tissues, or cells, nor are they
      necessarily irreversible. Surgical procedures can restore mobility for many
      patients with age-related musculoskeletal injuries or degenerative diseases.
      Regular resistance and range-of-motion exercises can decrease the age-related
      loss of strength and help maintain or restore flexibility. However, exercise
      programs can also cause injury. Older individuals should have a careful medical
      evaluation before starting an exercise program, and the program should be
      selected based on this evaluation. This is especially important for individuals
      with systemic illness and for individuals at greater risk of musculoskeletal
      injury, including people with previous joint injuries, obesity, osteoarthritis,
      joint deformity, weakness, or restricted joint motion. Trophic hormone
      replacement or supplementation may also modify age-related changes in the soft
      tissues, including loss of strength, but these hormones have adverse effects.
      Systemic or local use of growth factors and cell transplantation after expanding
      the population of mesenchymal stem cells in culture could improve healing in
      older people. Other potential methods of slowing or reversing age-related
      deterioration of the soft tissues include inhibition of posttranslational
      modification of matrix proteins and alteration of the activity of selected
      transcription factors. In particular, better understanding of the role of
      transcription factors in cell sequence may make it possible to devise methods of
      delaying or reversing age-related loss of cell proliferative and synthetic
      capacity.

PMID- 9143989
TI  - Growth factors as therapeutic agents.

PMID- 9143990
TI  - Growth factor treatment of disorders of skeletal growth.

PMID- 9143991
TI  - Growth factor treatment of fractures.

PMID- 9143992
TI  - Effects of growth factors on cartilage repair.

PMID- 9143993
TI  - Growth factors as potential therapeutic agents in osteoporosis.

PMID- 9143994
TI  - Current concepts: amputation surgery in peripheral vascular disease.

PMID- 9143995
TI  - Amputation versus limb salvage.
AB  - The decision to attempt salvage or to amputate a severely injured leg in among
      the most difficult that the orthopaedist must face. Even surgeons with tremendous
      trauma experience cannot agree on standard course of action. In the face of such
      injuries, physician consultation regarding the treatment decision, including all
      of those members of the team that are needed for a successful salvage, is
      necessary. In the best circumstances, the trauma surgeon, vascular surgeon,
      orthopaedist, and a soft-tissue specialist are all involved. From a psychological
      perspective, the timing of an amputation is important. Although each patient's
      case is unique, immediate amputation is often viewed by the patient and family as
      a result of the injury. Conversely, a delayed amputation may be viewed as a
      failure of treatment. It is imperative that the surgeon have a detailed
      discussion with the patient and the family whenever possible before making the
      decisions. Scoring systems are of some help in estimating the chances of a
      successful salvage. However, the ultimate decision to amputate or attempt salvage
      is based on such patient factors as preinjury function and social situation, and
      of associated injuries, surgeon experience, available resources, projected
      physical abilities, and the patient's projected physical requirements. These
      decisions are difficult and tax the judgment and emotions of the patient, family,
      and physician.

PMID- 9143996
TI  - Advanced imaging in orthopaedics: current pitfalls and new applications.

PMID- 9143997
TI  - Bioresorbable implants: applications in orthopaedic surgery.
AB  - There are several new and potential uses for absorbable implants. Some will
      provide exciting options in the future. Ongoing animal and clinical studies will
      help focus future areas of development.

PMID- 9143998
TI  - Patient management during limb lengthening.

PMID- 9143999
TI  - Prevention of deep periprosthetic joint infection.

PMID- 9144000
TI  - Tendon problems in athletic individuals.

PMID- 9144001
TI  - Clinicians teaching orthopaedics: effective strategies.

PMID- 9144003
TI  - The role of medical professionals in smoking control in Japan.

PMID- 9144002
TI  - The use of computer technology to improve the effectiveness of orthopaedic
      presentations.

PMID- 9144004
TI  - Neurologic manifestations in human immunodeficiency virus infection/acquired
      immunodeficiency syndrome.

PMID- 9144005
TI  - Relation between smoking status of physicians and their enthusiasm to offer
      smoking cessation advice.
AB  - Are nonsmoking physicians more likely to give smoking cessation advice to their
      patients? To determine this, we sent a questionnaire individually to physicians
      in Tokyo. The average age of the 323 respondents was 59.8 +/- 12.9 (mean +/- SD);
      84.8% of them were male and 21.1% were smokers. Among the respondents, 88.8%
      asked their patients about their smoking status, 79.9% advised smoking patients
      to stop, and 93.5% believed smoking cessation interventions to be necessary.
      Nonsmoking physicians were more likely to advise patients to stop smoking (85.6%)
      than smoking physicians (70.1%); the smoking physicians who themselves wished to
      reduce cigarette consumption or stop smoking were more likely to do so (85.0%)
      than those who did not wish to reduce or stop (43.5%). Moreover, more nonsmoking
      physicians seriously felt that smoking cessation interventions are necessary
      (31.2%) than did smoking physicians (6.5%). In conclusion, the smoking status and
      attitude towards smoking of physicians influences their enthusiasm to give advice
      to their patients against smoking.

PMID- 9144006
TI  - Serum levels of soluble Fas/APO-1 receptor in human retroviral infection and
      associated diseases.
AB  - Fas/APO-1 mediates apoptosis via Fas and Fas ligand transduction. Recently, a
      soluble form of Fas (sFas) was described which seems to be functionally
      implicated in the Fas signal system, suggesting a relationship between some
      disorders and sFas function. We measured sFas-levels in sera from normal controls
      and patients with disorders linked to human retroviral infection of human
      immunodeficiency virus (HIV) and human T-cell leukemia virus type-1 (HTLV-1). The
      sFas level of normal controls. HTLV-1 carriers seronegative for HIV, and patients
      with HTLV-1 associated myelopathy/tropical paraparesis (HAM/TSP), adult T-cell
      leukemia (ATL), and AIDS was 1.62 +/- 0.49, 1.90 +/- 0.49, 2.00 +/- 0.59, 3.32 +/
      2.05, and 3.06 +/- 0.92 ng/ml, respectively. Although the level of sFas in
      patient groups with HAM/TSP, ATL, and AIDS was significantly high in comparison
      to that of normal controls (p < 0.01), the individual values were highly variable
      within the groups. The sFas level was statistically correlated to the soluble
      interleukin-2 receptor (sIL-2R) level, as well as to cells expressing membrane
      Fas (mFas), indicating the same cellular origin. In some ATL cases, however,
      serum sFas levels and mFas expression density on leukemic T-cells were
      discrepant, with especially high levels of the soluble form and a lack of
      expression of the membrane form observed in 2 cases, sFas detection could serve
      as a putative marker for active diseases in patients with ATL and AIDS.

PMID- 9144007
TI  - Aeromonas bacteremia in patients with hematologic diseases.
AB  - Over a 23-year period, 17 patients with hematologic diseases developed Aeromonas
      bacteremia while in our hematology ward. Male predominance (14 patients, 82%) was
      seen, with a predilection for the elderly. Hematologic malignancies, especially
      acute leukemia, accounted for 15 (88%) of all patients. Cancer chemotherapy and
      neutropenia (15 patients each) were the most common preceding host conditions.
      Aeromonas bacteremia generally occurred in the second half of the year (July
      December), with no exposure to water or fish. Seven recent isolates comprised
      Aeromonas sobria (five isolates) and Aeromonas hydrophila (two isolates). Twelve
      patients (71%) showed a clinical picture ranging from mild gastroenteritis to
      severe enterocolitis. Anorectal and hepatobiliary infections were also noted in a
      few patients. The overall mortality rate was 35%. Ten (77%) of the 13 patients
      who were treated with aminoglycoside plus cephalosporin or carbapenem survived in
      association with marrow recovery.

PMID- 9144008
TI  - Nationwide survey of neurologic manifestations of acquired immunodeficiency
      syndrome in Japan.
AB  - To study the epidemiology of the neurologic manifestations of human
      immunodeficiency virus (HIV)-1 infection in Japan, we conducted two nationwide
      surveys. Of 1854 HIV-1 carriers, 578 had acquired immunodeficiency syndrome
      (AIDS) and 166 (28.7% of AIDS patients) had neurologic manifestations including
      HIV dementia (11.8%), myelopathy (3.6%) and peripheral neuropathy (2.6%). The
      incidence of neurologic manifestations in patients with HIV-1 infection through
      blood products was about 60% of that in patients with HIV-1 infection through sex
      or unknown routes. This nationwide survey showed that the incidence of neurologic
      manifestations in AIDS patients in Japan was consistent with that in other
      countries.

PMID- 9144009
TI  - Interleukin-13 but not interleukin-4 prolongs eosinophil survival and induces
      eosinophil chemotaxis.
AB  - The effects of recombinant human (rh) interleukin (IL)-4 or rhIL-13 on survival,
      and chemotactic activity of human eosinophils were examined. Only rhIL-13
      prolonged eosinophil survival in a dose-dependent manner above 3 ng/ml.
      Eosinophil survival induced by rhIL-13 was inhibited by monoclonal antibodies
      (mAbs) against IL-3 (p < 0.01) and granulocyte-macrophage colony-stimulating
      factor (GM-CSF) (p < 0.05), suggesting that rhIL-13 induced IL-3 and GM-CSF
      production from eosinophils and an autocrine mechanism is responsible for the
      eosinophil survival. The effects of rhIL-13 on eosinophil chemotactic activity
      were also examined. rhIL-13 showed chemotactic activity for eosinophils in a dose
      dependent manner. Checkerboard analysis revealed that eosinophil migration was
      dependent on the concentration gradient, confirming that rhIL-13 is a chemotactic
      factor. rhIL-4 showed no effects. IL-13 may play an important role in the
      survival and recruitment of eosinophils in allergic diseases.

PMID- 9144010
TI  - Giant hepatic angiomyolipoma associated with disseminated intravascular
      coagulation.
AB  - We report a case of giant hepatic angiomyolipoma in a 68-year-old woman who had
      an increase in the fibrinolytic activity concomitant with disseminated
      intravascular coagulation (DIC). The presence of the tumor was confirmed by
      ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) of
      the abdomen and the selective arteriography of the liver via the superior
      mesenteric artery. Following treatment with heparin and gabexate mesilate,
      abnormal hemostatic values were corrected. Furthermore, the surgical removal of
      the huge hepatic angiomyolipoma completely normalized the alternations of the
      clotting system. These findings suggest that giant hepatic angiomyolipoma was
      profoundly associated with DIC.

PMID- 9144011
TI  - Angiosarcoma of the heart presenting as fatal pulmonary hemorrhage.
AB  - A 47-year-old man died from fatal pulmonary hemorrhage. Cardiac angiosarcoma with
      lung metastases was found at postmortem examination. His chest radiograph showed
      bilateral, diffuse nodular infiltrates without cardiomegaly. No cardiac signs and
      symptoms were observed. The clinical outcome was rapidly fatal. Angiosarcoma of
      the heart should be suspected in patients with hemoptysis and nodular chest
      radiograph abnormalities, even in the absence of cardiac signs and symptoms.

PMID- 9144012
TI  - Reversibly increased lymphocyte response to mitogens in a young man with isolated
      adrenocorticotropic hormone deficiency.
AB  - A 21-year-old man with isolated adrenocorticotropic hormone (ACTH) deficiency
      complained of loss of consciousness in association with hypoglycemia. Both plasma
      ACTH and cortisol levels were low and failed to respond to corticotropin
      releasing hormone (CRH) stimulation. The patient also showed abnormal findings in
      hematological examination, such as neutropenia and anemia with lymphocytosis,
      activity of coagulation factors, and electroencephalography (EEG). Furthermore,
      mitogen-induced lymphocyte proliferation was increased. After successful
      replacement therapy with hydrocortisone 15 mg/day, most of these abnormalities
      including the lymphocyte proliferation were fully restored.

PMID- 9144013
TI  - Histamine poisoning after ingestion of spoiled raw tuna in a patient taking
      isoniazid.
AB  - An 83-year-old woman taking isoniazid (INH) suddenly developed a headache,
      palpitations, and skin eruptions with itching while eating raw tuna. The symptoms
      were compatible with those of histamine intoxication. When given fresh raw tuna
      to eat, no such reactions were evoked in this patient. The episode was speculated
      to be due to two conditions; eating spoiled raw tuna and at the same time being
      on a course of INH, a potent histaminase inhibitor. We should therefore be aware
      of the possible adverse effects due to the interactions between drugs and foods.

PMID- 9144014
TI  - Two cases of renal hypouricemia with nephrolithiasis.
AB  - We treated two cases of renal hypouricemia with nephrolithiasis. The serum uric
      acid level of the first patient was 1.5 mg/dl, and the ratio of uric acid
      clearance to creatinine clearance (CUA/Ccr) was 75.7%. In the benzbromarone (BZB)
      suppression test, CUA/Ccr was increased from 60.4% to 130.0%, but was not
      decreased in response to the pyrazinamide (PZA) suppression test. This patient
      was considered to have a presecretory reabsorptive urate transportation defect.
      His condition was also associated with IgA nephropathy. The serum uric acid level
      in the second patient was 1.0 mg/dl and CUA/Ccr was 56.0%. Neither PZA nor BZB
      had a significant effect on CUA/Ccr. He was considered to have a subtotal uric
      acid transportation defect. Both patients were incidentally found to have
      nephrolithiasis. The second patient had abnormal maximum tubular secretory
      capacity for para-aminohippurate (PAH) (TmPAH), and was found to have two kinds
      of proximal tubular abnormalities related to uric acid and PAH.

PMID- 9144015
TI  - Three cases of renal angiomyolipoma.
AB  - We report three non-typical cases of renal angiomyolipoma including clinical
      features, imaging examinations (with ultrasonography, computed tomography (CT),
      magnetic resonance imaging (MRI) and angiography) and histological findings.
      Microaneurysms observed by angiography were common to the three cases and were
      considered to be an important finding in the diagnosis of renal angiomyolipoma.
      Moreover, the short tau inversion recovery (STIR) method of MRI, which suppresses
      photon signals of fat, was considered to be useful for the diagnosis. Case 1 was
      accompanied by spontaneous rupture, Case 2 was difficult to diagnose because of
      little fat tissue and Case 3 revealed a very small tumor.

PMID- 9144016
TI  - Cervical tuberculous lymphadenitis in a frequent traveler to endemic areas of
      tuberculosis.
AB  - Scrofula or cervical tuberculous lymphadenitis (CTBL) should be suspected in
      patients with a history of potential exposure to tuberculosis present with
      cervical lymphadenopathy. A 55 year-old frequent traveler to Philippine and
      Thailand developed swelling of the bilateral cervical lymph nodes, and positive
      conversion of purified protein derivative of tuberculin (PPD) without pulmonary
      manifestations. The excisional biopsy of the cervical lymph nodes was useful for
      prompt diagnosis of CTBL, and the patient was successfully treated with isoniazid
      (INH) and rifampicin (RFP).

PMID- 9144017
TI  - Pneumonitis caused by saikokeisikankyou-tou, an herbal drug.
AB  - A 57-year-old man was admitted to our hospital because of dyspnea and abnormal
      shadow on chest roentgenogram. He had received two herbal drugs:
      Saikokeisikankyou-tou (SKT) for one month and Licium Halimifolium Mil (LHM) for
      two weeks. After admission, all medication was stopped and his symptoms were
      gradually diminished. Transbronchial lung biopsy specimens showed interstitial
      pneumonia. Lymphocyte stimulation test, skin test and challenge test were
      positive to these herbal drugs. We diagnosed him as drug-induced pneumonitis.
      This is the first report on pneumonitis caused by Saikokeisikankyou-tou diagnosed
      by lymphocyte stimulation test, skin test and challenge test.

PMID- 9144018
TI  - Disseminated intravascular coagulation associated with pulmonary tuberculosis.
AB  - Disseminated intravascular coagulation (DIC) is a very rare complication of
      pulmonary tuberculosis. We herein describe a case of cavitary tuberculosis
      complicated with DIC. Rifampin was considered to deteriorate the clinical course
      of DIC in this case.

PMID- 9144019
TI  - Fulminant septicemic syndrome of Bacillus cereus in a leukemic patient.
AB  - We report a rapidly fatal Bacillus cereus septicemia in a leukemic patient
      receiving remission-induction therapy. Symptoms resembling food poisoning and
      fever preceded coma accompanied by neurologic abnormalities. Autopsy revealed
      necrotizing leptomeningitis with subarachnoid hemorrhage and coagulation necrosis
      of the liver with bacterial infiltration. These clinicopathologic findings were
      closely similar to those of reported cases. Because of a rapidly fatal clinical
      course, suspicion of this syndrome early in the course is important to determine
      an appropriate treatment. Therefore, we propose that this type of septicemia
      should be termed as fulminant septicemic syndrome of Bacillus cereus.

PMID- 9144020
TI  - Co-existence of non-Hodgkin's lymphoma in the leukemic phase and polyarthritis
      simulating rheumatoid arthritis.
AB  - The patient, a 64-year-old male, complained of morning stiffness, polyarthralgia
      and bilateral knee joint swelling with leukocytosis (24,200/microliter) in
      peripheral blood. The leukocyte differentiation revealed 54% medium-size immature
      lymphocytes. The majority of lymphocytes showed the B-cell characteristics of
      IgGk monoclonality, and CD19+ and CD20+ in cell surface phenotype, suggesting a B
      cell malignancy, non-Hodgkin lymphoma in the leukemic phase. Arthropathy
      associated with lymphoid malignancy was suspected. However, the infiltrated
      leukocytes in the synovial fluid of the left knee joint were dominantly
      neutrophils and CD3+ T-cells, and compatible with the findings in rheumatoid
      arthritis (RA). The association of B-cell malignancy and RA is not frequently
      reported. We discuss the common underlying immunological abnormalities in both B
      cell malignancy and RA.

PMID- 9144021
TI  - Postoperative aggravation of hypercalcemia-leukocytosis syndrome in a case of
      squamous cell type cholangiocarcinoma.

PMID- 9144022
TI  - The genetic basis of atherosclerosis.
AB  - Atherogenesis is a complex process that involves the contributions of several
      pathophysiological sub-systems. The dissection of the genetic component of
      atherosclerosis has become possible using current molecular technologies and
      analytical methods. Genetic factors are considered to determine the limits under
      which atherosclerosis develops and environmental factors are considered to
      position an individual's risk within these limits. Atherosclerosis proceeds
      through a well-characterized series of pathological stages that involve key cell
      types and the expression of particular gene products. Reductionist experimental
      models have helped to produce a list of several hundred candidate genes for the
      study of the genetic component of atherosclerosis. Within certain families and
      isolated communities the effect of a single candidate gene upon atherosclerosis
      susceptibility may be profound, as in the case of mutations in the gene encoding
      the low-density lipoprotein receptor, which produce familial hypercholesterolemia
      and premature atherosclerosis. However, particular candidate genes have small
      effects on atherosclerosis or to one of its intermediate phenotypes, in whole
      populations. In addition, pleiotropy and epistasis can confound the
      identification of the genetic component of atherosclerosis. Despite these
      limitations, it might still be possible to use genetic information clinically in
      order to classify individuals who are susceptible to atherosclerosis, especially
      if as yet undiscovered candidate genes are found to be important determinants of
      disease. However, it will be impossible to predict the onset of a clinical
      manifestation of atherosclerosis in a particular person. This is due to the
      confounding influence of other forces, such as variations in interindividual
      environmental landscape, non-linear interactions between genes and environment,
      and even the possible influence of biological chaos.

PMID- 9144023
TI  - Lipoprotein(a): structural implications for pathophysiology.
AB  - The assembly between a low-density lipoprotein particle and apolipoprotein(a), a
      highly carbohydrate-rich protein, gives origin to a peculiar class of
      lipoproteins, only found in the hedgehog, primates, and humans, termed
      lipoprotein(a). Apolipoprotein(a), which shares a high degree of sequence
      homology with the fibrinolytic proenzyme plasminogen, is linked to the
      apolipoprotein B-100 component of low-density lipoprotein via a disulfide bond
      and confers distinct biochemical and metabolic properties to lipoprotein(a).
      Because of its peculiar structural features and the observed correlation between
      high lipoprotein(a) levels and the development of a variety of atherosclerotic
      disorders, this lipoprotein has become the focus of an intense research effort.
      Although accumulation of lipoprotein(a) in the vessel wall at sites of vascular
      injury has been clearly evidenced, the mechanism(s) by which lipoprotein(a)
      exerts its pathogenic effect in this milieu remain largely unknown. It has been
      hypothesized that the pathological effect of lipoprotein(a) is related either to
      its similarity to low-density lipoprotein (i.e., a pro-atherogenic effect) or to
      the apolipoprotein(a) similarity to plasminogen (i.e., a pro-thrombotic/anti
      fibrinolytic effect). However, it is probable that both components contribute to
      the pathogenicity of lipoprotein(a). The fact that lipoprotein(a) levels are
      largely genetically determined, varying widely among individuals and racial
      groups, adds additional elements to the scientific interest that surrounds this
      lipoprotein. Both clinical and biochemical studies of lipoprotein(a) have been
      complicated by the high degree of structural heterogeneity of apolipoprotein(a),
      which is considered the most polymorphic protein in human plasma. Our aim in this
      paper is to provide an overview of the most salient structural features of
      lipoprotein(a) and their possible pathophysiological implications.

PMID- 9144025
TI  - Gene therapy for atherosclerosis.
AB  - Although considerable progress has been made in the prevention and treatment of
      atherosclerotic cardiovascular disease, new therapeutic strategies are still
      needed. Atherosclerosis is a systemic disease and represents an attractive target
      for the development of somatic gene transfer intended to modulate systemic
      factors with the goal of inhibiting disease progression. This approach should be
      differentiated from localized vascular gene delivery to isolated atherosclerotic
      lesions such as that intended to prevent restenosis. Systemic gene therapy for
      atherosclerosis can involve either: 1) gene replacement therapy in patients with
      defined genetic disorder causing premature atherosclerosis, or 2) overexpression
      of proteins which directly or indirectly inhibit atherosclerosis or stabilize
      vulnerable lesions. The former is conceptually straightforward, and a pilot
      clinical gene therapy trial for one of these diseases, homozygous familial
      hypercholesterolemia, has already been reported. The latter has significant
      potential for eventual application to a large number of patients at risk for
      progressive atherosclerosis, independent of the specific cause. However,
      substantial progress in vector development and the demonstration of efficacy in
      relevant animal models will be required before gene therapy for atherosclerosis
      becomes a clinical reality.

PMID- 9144024
TI  - Lipoprotein lipase gene variants and risk of coronary disease: a quantitative
      analysis of population-based studies.
AB  - The purpose of this study is to quantify the magnitude of the association between
      common variants in the lipoprotein lipase gene and coronary disease, based on
      published population-based studies. Fourteen studies, representing 15,708
      subjects, report allelic distribution for lipoprotein lipase gene variants among
      coronary disease patients and control subjects. Patient outcomes included
      clinical coronary disease events and documented coronary disease based on
      angiography. Allele frequencies are estimated for disease and non-disease groups
      within each study. A 2 x 2 contingency table is used to compute individual study
      odds ratios and 95% confidence intervals, relating the presence of the rare
      allele to disease status. Mantel-Haenszel-stratified analysis of each allelic
      variant results in a summary odds ratio and 95% confidence interval for the
      association between each rare allele in the lipoprotein lipase gene and coronary
      disease. The lipoprotein lipase D9N allele has a summary odds ratio of 1.59 (95%
      confidence interval 1.03-2.55), indicating a 59% increase in risk of coronary
      disease for carriers with this allelic variant. The lipoprotein lipase N291S
      allele showed no association with coronary disease (summary odds ratio 0.93, 95%
      confidence interval 0.73-1.19). The summary odds ratio for lipoprotein lipase
      S447Ter allele is 0.81 (95% confidence interval 0.65-1.0), indicating a marginal
      negative association between this variant and coronary disease. The common
      lipoprotein lipase Pvu II polymorphism shows no relation to coronary disease
      (summary odds ratio 0.90, 95% confidence interval 0.80-1.01). The rare allele of
      the lipoprotein lipase HindIII polymorphism is negatively associated with
      coronary disease (summary odds ratio 0.84, 95% confidence interval 0.73-0.96).
      The lipoprotein lipase D9N allele is associated with high levels of triglyceride
      and low levels of high-density lipoprotein. Similar atherogenic lipid levels are
      observed in subjects with structural mutations lipoprotein lipase C188E and
      P207L. Carriers of the S447Ter allele have low levels of triglyceride. The
      lipoprotein, lipase gene variants which decrease lipoprotein lipase catalytic
      activity are associated with familial combined hyperlipidemia, but not the
      elevation of apolipoprotein B seen in this disorder. In conclusion, allelic
      variants in the lipoprotein lipase gene are associated with altered lipid levels
      and differential coronary disease risk.

PMID- 9144026
TI  - Glutathione protects a human insulinoma cell line from tumor necrosis factor
      alpha-mediated cytotoxicity.
AB  - It is postulated that glutathione acting as a free oxygen radical scavenger may
      protect beta-cells from cytokine-mediated cytotoxicity in insulin-dependent
      diabetes. In this study the effect of glutathione in preventing the cytotoxic
      damage mediated by tumor necrosis factor-a in vitro towards a human beta-cell
      line (CM insulinoma) was investigated. CM cells were exposed in vitro to tumor
      necrosis factor-alpha, tumor necrosis factor-alpha plus glutathione or
      glutathione alone at different concentrations. The resulting cytotoxicity was
      measured using a colorimetric assay. Glutathione significantly reduced the
      cytotoxicity mediated by tumor necrosis factor-alpha in a dose-dependent fashion
      (P < 0.001). These results suggest a protective effect of glutathione on beta
      cell cytotoxicity induced by tumor necrosis factor-alpha and encourage the use of
      glutathione in trials aimed at reducing the beta-cell damage occurring in insulin
      dependent diabetes.

PMID- 9144027
TI  - IgG M-components in active myeloma patients induce a down-regulation of natural
      killer cell activity.
AB  - Natural killer cell activity and related cell surface markers of peripheral blood
      lymphocytes were studied in 73 patients with multiple myeloma, 25 with monoclonal
      gammopathy of undetermined significance and 20 normal controls. Natural killer
      cell number was significantly higher in both multiple myeloma and monoclonal
      gammopathy patients than in controls, whereas the natural killer activity of
      multiple myeloma patients was inversely related to their disease status.
      Incubation of peripheral blood lymphocytes or natural killer cells with IgG
      myeloma proteins purified from several patients induced a down-modulation of
      basic natural killer activity. This inhibitory effect of monoclonal IgG was dose
      dependent and significantly stronger in patients with active (at diagnosis and at
      relapse) than stable multiple myeloma or in normal controls. Addition of
      exogenous recombinant interleukin-2 restored natural killer cell activity against
      K562 target cells, indicating that natural killer cells were able to recover
      their functions. However, recombinant interleukin-2-stimulated natural killer
      cells were responsive to down-modulation of monoclonal IgG. These data suggest
      that impaired natural killer cell function in active multiple myeloma is caused
      by the inhibitory effect of M-component.

PMID- 9144028
TI  - Increased resistance to oxidative stress in normal and glucose-6-phosphate
      dehydrogenase-deficient hemolysates in the presence of enzyme substrates.
AB  - Erythrocytes and hemolysates from 10 normal and 10 glucose-6-phosphate
      dehydrogenase-deficient individuals were incubated with cumene hydroperoxide, and
      free radical-induced lipid peroxidation was monitored by chemiluminescence.
      Chemiluminescence intensities in erythrocytes of normal and deficient subjects
      were similar in the presence or absence of glucose-6-phosphate dehydrogenase
      substrates. Hemolysates of normal and deficient subjects also showed similar
      chemiluminescence in the absence of substrates. However, with the addition of
      substrates to the incubation medium, deficient hemolysates reached maximum
      chemiluminescence intensity within a shorter period, and maximum values were
      higher than in normal hemolysates. We believe this offers a new means of
      detection of glucose-6-phosphate dehydrogenase-deficient patients.

PMID- 9144029
TI  - Rapid and specific immunoassay for cardiac troponin I in the diagnosis of
      myocardial damage.
AB  - We evaluated a new immunometric assay for the quantitation of cardiac troponin I
      with the Behring Opus analyzer. All assay steps are performed automatically by
      the analyzer, the complete procedure requiring 20 min for the first test result.
      Total precision (coefficient of variation) varied between 5.6% and 13.0%.
      Comparison with the Pasteur immunoenzymometric assay showed good correlation (r =
      0.959), but the Opus assay gave approximately tenfold higher values. Cardiac
      troponin I was undetectable (< 0.5 microgram/l) in sera from healthy subjects (n
      = 46), patients with severe skeletal muscle damage (n = 8), and all but 1 patient
      with chronic renal failure (n = 39). In patients with myocardial infarction (n =
      21), investigated for 4 days after onset by frequent sampling, cardiac troponin I
      peaked at 20.8 +/- 8.1 h after onset with a mean concentration of 164.8 +/- 361.3
      micrograms/l, remaining elevated in 89% of patients on the 4th day. In patients
      with unstable angina (n = 15), cardiac troponin I measurement was valuable in
      predicting the type of lesion morphology on coronary angiography and the short
      term outcome.

PMID- 9144030
TI  - D-dimer plasma levels during normal pregnancy measured by specific ELISA.
AB  - A progressive increase in D-dimer plasma levels together with an increase in
      fibrinogen has been previously reported during normal pregnancy. However,
      significantly different D-dimer levels have been observed in different assays,
      due to different specificity of the antibodies employed. The aim of this study
      was to verify the increase in fibrin degradation product levels during normal
      pregnancy, using a recently introduced specific D-dimer ELISA. We determined D
      dimer (ELISA) and fibrinogen (clotting method) plasma levels in 63 normal
      pregnant women, during three different periods of pregnancy (A, 7-20 weeks; B, 21
      30 weeks; C, > 30 weeks). During period A, D-dimer plasma levels (range 2-103
      ng/ml) showed an insignificant increase compared with a control group of non
      pregnant women (range 2-73 ng/ml). During periods B and C, we observed an
      increase in D-dimer level (P < 0.0001) compared with period A, with a significant
      correlation between D-dimer levels and gestational age (P < 0.0001). Period A
      fibrinogen levels (range 3.24-6.43 g/l) were significantly higher (P < 0.0001)
      than in controls (range 2.31-4.71 g/l), with a further increase in periods B and
      C. In conclusion, we confirmed a progressive increase in plasma concentrations of
      fibrin degradation product during normal pregnancy, but D-dimer levels were
      significantly lower than those reported in the literature for other ELISAs.

PMID- 9144031
TI  - Coagulation factor XIII in pregnant smokers and non-smokers.
AB  - Human blood coagulation factor XIII is a transglutaminase zymogen. Two forms
      exist, an extracellular or plasma factor XIII and an intracellular form. Factor
      XIII occurs in platelets, blood, monocytes, megakaryocytes, the liver, the
      placenta, and the uterus. In obstetrics, factor XIII deficiency has been
      associated with fetal wastage. The interaction of smoking and the quantity of
      coagulation factor XIII during normal pregnancy was examined in 75 non-smoking
      and 118 smoking (> or = 20 cigarettes/day) women. A group of subjectively
      healthy, non-smoking, age-matched females served as a control group (n = 30).
      Smokers had a higher plasma concentration of factor XIII than non-smokers. Factor
      XIII declined during normal gestation. During the second half of gestation the
      plasma concentration of factor XIII was significantly higher in smokers than in
      non-smokers. In smokers the decline of factor XIII was less, possibly due to
      platelet activation and a relative polycythemia. The later decline of factor XIII
      in pregnant smokers remains unexplained. More extensive research with larger
      patient numbers is needed to address this matter.

PMID- 9144032
TI  - Increased thrombin generation in patients with chronic renal failure.
AB  - The plasma concentration of prothrombin fragment 1 + 2 (F1 + 2) is considered a
      very sensitive parameter for specific detection of latent hypercoagulability. To
      evaluate the degree of hypercoagulation associated with chronic uremia, we
      measured F1 + 2 by ELISA in the plasma of 51 patients with severe or end-stage
      chronic renal failure (35 males, 16 females, aged 22-81 years): 24 on dietary
      treatment 15 on combined dietary and once a week hemodialysis, and 12 on regular
      maintenance hemodialysis; 33 healthy subjects served as a control group. Plasma
      F1 + 2 showed a significant elevation in the group on dietary treatment; it was
      further increased in the group on once a week hemodialysis, and even more
      markedly increased in the group on maintenance hemodialysis. In patients on
      dietary treatment a positive correlation was found between plasma F1 + 2 and
      serum creatinine. In patients on maintenance hemodialysis, no increase in the F1
      + 2 plasma level was found during the course of a single hemodialysis session.
      Low molecular weight heparin, administered to 7 patients on dietary treatment,
      caused a marked drop in the F1 + 2 plasma level, providing evidence that the
      elevation in F1 + 2 indicates an accelerated in vivo thrombin generation rather
      than impaired renal catabolism. The enhanced coagulation activation appears to be
      related to the reduction of residual renal function, i.e., to the severity of
      renal failure, and may contribute to the increased risk of vascular events in
      uremic patients.

PMID- 9144033
TI  - Are prothrombin fragment 1 + 2 and thrombin-antithrombin complexes useful in the
      management of oral anticoagulant therapy?
AB  - We investigated the behavior of prothrombin fragment F1 + 2 and thrombin
      antithrombin complexes in 70 patients treated with chronic anticoagulant therapy.
      Moreover, in a longitudinal study 37 patients were evaluated twice and 16
      patients three times. Twenty-eight age- and sex-matched healthy subjects were
      also studied as a control group. Prothrombin fragment F1 + 2 or thrombin
      antithrombin values among patients with different International Normalized
      Ratios, nor in the same patients studied two or three times. Our results confirm
      that oral anticoagulant treatment can effectively reduce thrombin activity.
      However, strong anticoagulation does not induce a further significant decrease in
      fragment F1 + 2 values. Therefore, we feel measurement of fragment F1 + 2 might
      be less useful than thought in optimizing oral anticoagulant therapy.

PMID- 9144034
TI  - Successful treatment of common variable immunodeficiency and related disorders
      with cimetidine and zinc sulfate.

PMID- 9144035
TI  - Supportive and negative responses in the partner relationship: their association
      with psychological adjustment among individuals with cancer.
AB  - This study examined the association between positive and negative aspects of
      spouse responses and psychological adjustment among 158 individuals with cancer.
      Two contextual variables, gender and disease-related functional impairment, were
      taken into account when examining the association between spouse responses and
      patient psychological distress and well-being. Results indicated that negative
      aspects of close relationships played a comparatively stronger role than positive
      aspects in their associations with both psychological distress and well-being.
      For negative spouse responses, patient gender did not moderate the effects of
      these responses upon psychological outcomes. For positive aspects of spouse
      support, both gender and functional disability moderated the association between
      spouse support and psychological outcomes. These findings are integrated with the
      general literature on positive and negative aspects of close relationships.
      Implications for clinical interventions are also discussed.

PMID- 9144036
TI  - Predictors of childbirth pain and maternal satisfaction.
AB  - There is little multivariate, multiphasic research on childbirth pain and
      satisfaction. We explored the relationship of demographic, medical,
      psychological, and environmental variables at different times to multiple indices
      of pain and satisfaction in 70 primiparae and multiparae. Induced labor,
      desirability of pregnancy, and coach's helpfulness predicted sensory pain.
      Duration of labor, depression, and outcome expectancy that childbirth education
      would facilitate medication-free childbirth predicted affective pain. Physician
      anticipated complications, induced labor, and motivation to be medication-free
      predicted pain intensity. Grade level predicted-satisfaction. The results also
      demonstrated differences between primiparae and multiparae in the pattern of
      variables that explained pain and satisfaction as well as the temporal
      sensitivity of pain predictors. We discuss the implications of our findings for
      research and practice.

PMID- 9144037
TI  - Take Heart II: replication of a worksite health promotion trial.
AB  - The purpose of this study was to evaluate the effects of a revised worksite
      health promotion program that featured an employee steering committee/menu
      approach to intervention. The "Take Heart II" program was evaluated using a quasi
      experimental matched-pair design with worksite as the unit of analysis.
      Experimental and control worksites did not differ on baseline organizational or
      employee demographic variables or on baseline levels of dependent variables.
      Outcome and process results revealed consistent, but modest effects favoring
      intervention worksites on most measures. Cross-sectional analyses generally
      failed to produce statistically significant intervention effects, but cohort
      analyses revealed significant beneficial effects of the Take Heart II
      intervention on eating patterns, behavior change attempts, and perceived social
      support. Neither analysis detected a beneficial effect of intervention on
      cholesterol levels.

PMID- 9144038
TI  - Hostility, social support, and ambulatory cardiovascular activity.
AB  - The present study compared ambulatory blood pressure in male and female subjects
      preselected for high and low hostility levels and investigated interpersonal
      daily stress as a possible mediational mechanism. Ambulatory blood pressure and
      heart rate were measured in 48 male and female students previously classified as
      high or low on the Cook-Medley Hostility (Ho) Scale. Subjects wore an ambulatory
      monitor for a working day and also completed measures of perceived social
      support, daily interpersonal stress, and health behavior information. Results
      indicated that subjects scoring high on the Ho scale had higher mean levels of
      ambulatory systolic blood pressure than low Ho subjects, even when controlling
      for traditional risk factors, such as cigarette smoking. High Ho subjects also
      reported greater daily interpersonal stress and less social support than low Ho
      subjects. Perceived interpersonal stress partially accounted for the relationship
      between hostility and blood pressure. Subjects high in hostility showed greater
      mean ambulatory systolic blood pressure levels. Consistent with the transactional
      model of hostility and health, the relationship between hostility and blood
      pressure appears to be partially accounted for by the daily experience of
      interpersonal stress.

PMID- 9144040
TI  - Validating the MPI-DLV using experience sampling data.
AB  - The present study investigates the relationship between scale scores on the Dutch
      version of the Multidimensional Pain Inventory (MPI-DLV) and data derived from
      comparable items from an experience sampling procedure. Fifty-seven chronic pain
      patients participated in the study, which lasted 6 consecutive days. Special
      attention was given to the relationship between the MPI-DLV pain intensity score
      and the mean experience sampling pain intensity score. Significant correlations
      were found between the MPI-DLV scales Pain Severity, Interference, Solicitous,
      Punishing and Distracting Responses, and Household Chores and their experience
      sampling analogues. A marginally significant correlation was found with regard to
      the MPI-DLV Life Control scale. The General Activity and Affective Distress
      scales had no relationship with the analogous experience sampling items. The
      significant correlations were regarded as further validation of the MPI-DLV. A
      regression analysis revealed that 58% of the variance of the experience sampling
      pain intensity score could be explained by the MPI-DLV present pain intensity
      item score.

PMID- 9144039
TI  - The relationship between daily life stress and gastrointestinal symptoms in women
      with irritable bowel syndrome.
AB  - Research on irritable bowel syndrome (IBS), a functional disorder of the
      gastrointestinal (GI) system, has linked GI symptoms to stress. This study
      examined the relationship between daily stress and GI symptoms across women and
      within woman in IBS patients (n = 26), IBS nonpatients (IBS-NP; n = 23), and
      controls (n = 26), controlling for menstrual cycle phase. Women (ages 20-45)
      completed daily health diaries for two cycles in which they monitored daily GI
      symptoms and stress levels. The Life Event Survey (LES) was used as a
      retrospective measure of self-reported stress. The across-women analyses showed
      higher mean GI symptoms and stress in the IBS and IBS-NP groups relative to
      controls but no group differences in LES scores. The within-woman analyses found
      a significant and positive relationship between daily stress and daily symptoms
      in both the IBS-NP and the IBS groups. Controlling for menstrual cycle had no
      substantial impact on the results.

PMID- 9144041
TI  - Skin type and optimistic bias in relation to the sun protection and suntanning
      behaviors of young adults.
AB  - The study examined the roles of general and personal beliefs and skin type in
      relation to suntanning and sun protection, by assessing various perceptions of
      risk of skin cancer both for the self and for the average person. A sample of 355
      people aged 16 to 25 years was selected randomly from the telephone directory of
      a coastal provincial city. Highly structured interviews were conducted over the
      telephone. The findings were presented in relation to three research questions.
      First, skin type, classified as burn only, burn then tan, or tan without burning,
      influenced both general and personal beliefs. Compared to the tan-only group, the
      burn-only group perceived earlier age at onset, greater number of years of life
      lost, and greater severity of skin cancer, for both the average person and the
      self, and greater susceptibility to skin cancer for the average person. Second,
      differences were found between personally relevant and population-relevant
      beliefs on susceptibility to skin cancer, time of onset, and years of life lost
      due to skin cancer but not for perceptions of severity and curability. Finally,
      skin cancer beliefs were poor correlates of tanning and protecting behaviors. The
      factor explaining the greatest proportion of variance in both behaviors was skin
      type.

PMID- 9144042
TI  - Dentine hypersensitivity and the placebo response. A comparison of the effect of
      strontium acetate, potassium nitrate and fluoride toothpastes.
AB  - A considerable number of varied agents are apparently effective in the treatment
      of dentine hypersensitivity. In particular, the literature supports the efficacy
      of strontium, potassium and fluoride containing toothpastes. This study was a
      double-blind, randomised, parallel group comparison of three products, namely
      strontium- and potassium-based desensitising toothpastes both containing
      fluoride, and a conventional fluoride toothpaste. A total of 131 subjects entered
      a 4-week wash-in phase using the conventional fluoride toothpaste, of whom 120
      entered a 6-week treatment phase. Sensitive teeth were evaluated at wash-in
      baseline, treatment baseline and after 2 and 6 weeks use of the treatment pastes.
      Dentine hypersensitivity was assessed with tactile and cold air stimuli together
      with an overall subjective assessment. Analysis of the findings was performed
      using non-parametric statistical methods. Of the original 120 subjects, 112
      completed the trial. All 3 toothpaste groups showed reductions in sensitivity
      over the 6 weeks; however, no significant differences were found between the
      three products at any given time. Interestingly, there was no significant change
      in sensitivity between wash-in baseline and treatment baseline for the cold air
      stimulus with the fluoride-only-based paste. However, for the group using the
      same fluoride toothpaste, there was significant improvement between wash-in
      baseline and week 6, and treatment baseline and week 6 for this stimulus,
      suggesting a substantial placebo effect occurred. There is a need for further
      investigation of a wash-in period and examination of the placebo effect when
      evaluating dentine hypersensitivity trials.

PMID- 9144043
TI  - Inhibition of experimental gingivitis in beagle dogs with topical salivary
      histatins.
AB  - Histatins, histidine-rich proteins found within parotid and submandibular
      secretions, are a novel class of endogenous peptides with antimicrobial
      properties. This masked, randomized, placebo-controlled preclinical investigation
      examined the effect of 3 topical histatins on the development of plaque and
      gingivitis in beagle dogs. 16, female, 1-year-old beagles were brought to optimal
      gingival health by mechanical scaling and polishing followed by rigorous daily
      tooth brushing. At the conclusion of this pretreatment period, dogs were randomly
      divided into 4 groups for the application of test formulations, and were placed
      on a plaque-promoting diet. Test agents included 3 synthetic salivary histatins
      (histatin 5, P-113 and P-113D) which were incorporated in hydroxypropyl
      methylcellulose gel at a concentration of 0.125%, and a placebo, or negative
      control, which was the gel vehicle alone. Throughout the 10-week treatment
      period, test formulations (2.0 ml) were applied 2 x daily to all premolar teeth
      using a Monojet syringe. Plaque formation and gingival inflammation were assessed
      using the plaque (PI) and gingival (GI) indices on days 0, 7, 14, 21, 28, 42, 56
      and 70. Furthermore, bleeding to probing was recorded as a percent of sites
      (%BOP) and according to the modified sulcus bleeding index (mSBI). Comparisons
      among groups and between group pairs (active versus placebo) were made with
      Kruskal-Wallis tests with the average of data over the interval, days 14-42,
      being the primary focus of the analysis. From baseline to day 7, all groups
      expressed similar indices. Thereafter, overall significant differences among the
      groups were noted at day 42 for PI, at days 21, 28, 42 and 70 for GI, and at days
      14 and 28 for %BOP (p < 0.05). In particular, beagles treated with P-113
      demonstrated significantly lower PI scores at day 42 (p < 0.05), significantly
      lower GI scores from days 21 through 42 (p < 0.05), and significantly lower %BOP
      scores at days 14 and 28 (p < 0.05) compared to beagles treated with placebo.
      Beagles treated with P-113D exhibited significantly lower GI at day 42 compared
      to the placebo (p < 0.05). For the primary analysis conducted over the
      midtreatment interval (days 14-42), significant differences were detected for all
      parameters except mSBI (p < 0.05). Accordingly, significantly lower PI scores
      were found for P-113, lower GI scores for P-113 and P-113D, and lower %BOP for P
      113 and P-113D compared to placebo (p < 0.05). These data indicate that in the
      beagle model, salivary histatins, P-113 and P-113D, topically applied, can
      significantly reduce clinical signs of plaque formation and gingival
      inflammation.

PMID- 9144044
TI  - Behavioral risk indicators of attachment loss in adult Floridians.
AB  - This study investigated behavioral and sociodemographic risk indicators of
      attachment loss (AL) at baseline in subjects of the Florida Dental Care Study:
      873 subjects with at least 1 tooth, and who were 45+ years or older, participated
      for an in-person interview and dental examination; 761 subjects were probed for
      AL. Calibrated examiners used a modified NIDR protocol from the 1985-86 Survey of
      US Employed Adults and Seniors. Results were weighted to reflect actual
      population proportions. 92% of subjects had at least 1 site of 4+ mm AL, and 35%
      had at least 1 severe site (7+ mm AL). In a single multivariate regression, not
      having a recent dental check-up, not using dental floss, being a current smoker,
      and being diabetic were significantly associated with a higher probability of
      having 1 or more severe sites. Blacks were less likely than whites to be regular
      users of dental care, use dental floss, and be non-smokers. Similar findings were
      found for low income adults and rural residents. Risk groups (low income, blacks,
      rural residents) were more likely to present with modifiable risk indicators for
      AL, suggesting the need for targeted interventions.

PMID- 9144045
TI  - A combined surgical and orthodontic treatment of Class III furcations. Report of
      a case.
AB  - Oral hygiene in furcation defects of upper molars is difficult to achieve. In
      this case report, a combined surgical and orthodontic treatment procedure is
      presented to facilitate access and plaque control in furcation areas of upper
      molars with class-III furcation defects. After endodontic treatment and root
      resection in an upper 1st molar, the remaining mesiobuccal and palatal roots were
      separated and aligned orthodontically within the dental arch, as one-rooted
      teeth. The new morphological position of the roots greatly facilitated oral
      hygiene and may offer a better long-term prognosis.

PMID- 9144046
TI  - Release and activation of human neutrophil matrix metallo- and serine proteinases
      during phagocytosis of Fusobacterium nucleatum, Porphyromonas gingivalis and
      Treponema denticola.
AB  - The phagocytic ingestion of reference strains and clinical isolates of
      Fusobacterium nucleatum, Porphyromonas gingivalis, and Treponema denticola by
      polymorphonuclear leukocytes (PMNs) and the concomitant release of PMN granule
      proteinases were studied by specific functional and immunological assays. PMNs
      were incubated with the microorganisms anaerobically at 37 degrees C for
      indicated time periods. The suspensions and pellets were used for phagocytic
      ingestion assay and electron microscopic study, respectively. The supernatants
      were used for the measurements of the amounts and activities of the released PMN
      enzymes including PMN gelatinase (MMP-9), collagenase (MMP-8), serine proteases
      (elastase and cathepsin G), and lactate dehydrogenase (LDH). Both fluorescence
      microscopy and transmission electron microscopy showed that F. nucleatum, P.
      gingivalis and T. denticola were ingested by the PMNs in comparable numbers.
      However, measurements of the enzymes released from the triggered PMNs revealed
      major differences among the three species. High amount of elastase was released
      from the PMNs triggered by F. nucleatum, but not by P. gingivalis or T.
      denticola. The treatment of PMNs with P. gingivalis whole cells resulted in the
      release of gelatinase partly in the 82 kD active form, suggesting proteolytic
      activation of the degranulated 92 kD proMMP-9. The 82 kD active form of
      gelatinase was not detected upon triggering the PMNs with F. nucleatum and T.
      denticola. The PMN-bacteria interaction did not result in release of LDH from
      triggered PMNs indicating the proteinase release was not due to the PMN cell
      death. The results show that the susceptibilities of the 3 potentially
      periodontopathogenic microorganisms, F. nucleatum, P. gingivalis and T. denticola
      to phagocytic ingestion are not directly related to the amounts and activities of
      PMN enzymes released during the bacteria-PMN interactions. As PMN degranulation
      is considered as one of the major pathogenic mechanisms in periodontitis, the
      observed differences among the microorganisms may be important virulence
      characteristics of these species.

PMID- 9144047
TI  - A randomized controlled trial of a 2% minocycline gel as an adjunct to non
      surgical periodontal treatment, using a design with multiple matching criteria.
AB  - Topical locally delivered minocycline is an adjunctive to non-surgical
      periodontal treatment, but there are few reported trials. Previous trials have
      reported differences between changes in probing depth in treatment and control
      groups, but no differences in probing attachment level. In the present study, 30
      subjects were paired according to gender, age, ethnic group, smoking habits, and
      probing depths. Both groups received intensive oral hygiene education and root
      planing with local anaesthesia. Active or placebo gel was placed subgingivally at
      planed sites in each subject according to a double-blind protocol, immediately
      after instrumentation, and 2 and 4 weeks later. A periodontal examination was
      made with a constant force probe before instrumentation, and 6 and 12 weeks
      later, 2 subjects failed to complete the study, and their pairs were therefore
      not included in the analysis. Results were tested with analysis of covariance.
      Differences between groups in mean probing depth did not reach statistical
      significance at any visit (baseline: test (T) = 5.93 mm, control (C) = 5.74 mm; 6
      weeks: T = 3.53 mm, C = 3.63 mm; 12 weeks: T = 3.29 mm, C = 3.44 mm), but mean
      probing attachment levels were different (p < 0.05) at both reassessments
      (baseline: T = 6.86 mm, C = 6.83 mm; 6 weeks: T = 4.93 mm, C = 5.30 mm; 12 weeks
      T = 4.91 mm, C = 5.27 mm). There was also a difference in the number of sites
      with bleeding on deep probing at 12 weeks (p < 0.05). This trial showed that
      adjunctive minocycline gel provided a more advantageous outcome for nonsurgical
      periodontal treatment in terms of probing attachment level and bleeding on deep
      probing. This trial was a good example of experimental, as opposed to community,
      design, and used limited resources to show a clear result.

PMID- 9144048
TI  - Development of resistance to metronidazole and minocycline in vitro.
AB  - By local delivery of antibiotics to periodontal pockets, very high initial
      concentrations are often quickly succeeded by subinhibitory concentrations, which
      may facilitate development of bacterial resistance. The purpose of the present
      study was to investigate possible development of resistance in suspected
      periodontal pathogens after exposure to subinhibitory concentrations of
      metronidazole and minocycline. The minimal inhibitory concentration (MIC) of 18
      reference strains and 12 clinical isolates was determined by a broth dilution
      method. Subsequently, all strains with MIC < 8 micrograms/ml were exposed to
      serial passage on plates containing subinhibitory and gradually increasing
      concentrations of antibiotics, until growth was inhibited. Initially, most
      strains were inhibited at < or = 0.250 microgram/ml of minocycline and < or = 0.5
      microgram/ml of metronidazole, though A. actinomycetemcomitans was resistant to
      metronidazole. After growth at subinhibitory concentrations, 8 strains survived 1
      2 x and 11 stains survived 8-32 x their initial MIC of metronidazole, growing at
      up to 8 micrograms/ml. All A. actinomycetemcomitans survived 8-64 x their initial
      MIC of minocycline, growing at > or = 2 micrograms/ml, while all other strains
      were inhibited at < or = 0.250 microgram/ml, corresponding to a 1-8 x increase in
      their initial MIC. Thus, development of resistance was observed for periodontal
      bacteria growing at up to 64 x their initial MIC, but the final level of
      resistance was moderate.

PMID- 9144049
TI  - A clinical comparison of 2 electric toothbrush designs.
AB  - A single blind 30 day study compared the reduction of plaque and gingivitis for
      the Hapika Powerbrush to the Interplak ultra 10 tuft. A longitudinal parallel
      group design was utilized and screening evaluation was performed to determine
      patient eligibility prior to study enrollment, 66 subjects were entered into the
      study and assigned to 1 of 2 groups, each using one of the toothbrushes. At
      baseline, subjects received an oral soft tissue exam, a dental hard tissue exam,
      and were scored by the Lobene modification of the Loe and Silness gingival index
      (GI). Plaque was then disclosed and scored both pre and post brushing using the
      modified Turesky plaque/debris examination and an interproximal bleeding
      examination was performed post-brushing. On days 15 and 30, after an oral soft
      tissue and GI examination, plaque was graded by the Modified Turesky
      plaque/debris exam. Subjects then brushed and were graded by the Modified Turesky
      plaque/debris examination and an interproximal bleeding index examination. The
      results showed that both brushes provided a similar change in clinical indices.
      All produced a statistically significant reduction from baseline to day 30 for
      the gingival index (26.5-29.1%), the bleeding index (13.8-24.1%), and the plaque
      index (16.9-19.4%). A comparison of pre and post brushing scores for the plaque
      index at 30 showed that both brushes reduced plaque similarly with a
      statistically significant reduction (P < 0.05) from their pre-brushing plaque
      index scores at all time periods.

PMID- 9144050
TI  - Citric acid demineralization of cementum and dentin: the effect of the storage
      medium.
AB  - The purpose of this study was to see if the root surface topography of teeth,
      stored in saline and subsequently treated with citric acid, differred from the
      root surface topography of teeth that were treated immediately upon extraction,
      12 freshly extracted adult human permanent teeth, with proximal surfaces free of
      caries and periodontal disease, were treated in succession. The crowns were
      removed at the level of periodontal attachment, the teeth sectioned buccal
      lingually and a treatment area deligniated on each proximal section. The
      treatment area of 6 teeth was root planed to expose dentin (D) and scaled to
      remove adherent tissue and leave a cementum surfaces (C) on the other 6 teeth. A
      coronal-apical groove down the middle of the treatment area divided it into
      approximately equal parts or experimental regions. One proximal section of each
      tooth was placed in physiologic saline (S) and treated after 6 weeks of storage
      while the other proximal section was freshly treated (F). Treatment consisted of
      applying a 30% citric acid (CA) solution (pH = 1.60) for 5 min. Cotton pellets
      soaked in the citric acid solution were placed (P) on one half of the
      experimental area and heavily burnished (B) on the other half. Treatment areas
      were subsequently prepared for scanning electron microscopy analysis. Assessment
      was made of (i) the % of surface area tufted, (ii) fibril tufting depth (0.3) and
      (iii) fibril tufting density (1.3). Similarities were found in the data for both
      storage methods (F and S) across each application technique (P or B) and each
      tooth surface (D or C) with respect to the (i) % area tufted and (ii) frequency
      distribution of tufting depth scores. As for the application techniques, the data
      for burnishing was greater than placed across each storage method (F or S) and
      each tooth surface (D or C) for the same two parameters. The results of the study
      indicated that 6-week physiologic saline storage does not affect root surface
      demineralization by citric acid, as assessed by SEM.

PMID- 9144051
TI  - Factors related to Periotest values in endosseal implants: a 9-year follow-up.
AB  - Periotest values (PTV) of successful endosseal implants of 2 one-stage implant
      systems. TPS and ITI, were followed from 3 months to 9 years in order to
      determine the factors that contribute to the values. 128 TPS screw implants were
      inserted in the lower jaw of 34 subjects, (mean age 55 years), for retaining
      overdentures. 108 ITI implants were inserted in the upper and lower jaws in 50
      subjects (mean age 42 years), for retaining overdentures, crowns and bridges.
      PTVs were first measured after the osseointegration period and thereafter
      annually. First of all there was a difference between the 2 implant systems. Mean
      PTVs of TPS bicortical screws were significantly lower (P < 0.05) than those of
      ITI implants (screws, hollow-screws, hollow-cylinders). Factors which
      significantly contributed to PTVs of ITI implants were jaw (upper/lower), implant
      length and region of the jaw in which the implant was inserted. PTVs of ITI
      implants in the lower jaw were lower than in the upper jaw (P < 0.05). The length
      of implant had no effect on PTVs in the lower jaw, but in the upper jaw, PTVs of
      ITI 8-10-mm implants were lower than 12-mm implants (P < 0.05). PTVs of implants
      inserted in the anterior region of the upper jaw were higher than those in the
      posterior region (P < 0.05). In conclusion, bone quality and implant length had a
      statistically significant effect on implant mobility in long-term follow-up. PTVs
      of various implant systems, however, differ, a fact that must be taken into
      account in evaluating the success of implants.

PMID- 9144052
TI  - Blind nasotracheal intubation in the presence of facial trauma.
AB  - Blind nasotracheal intubation (BNTI) is an effective procedure for the intubation
      of trauma patients. The presence of major facial trauma has been considered a
      relative contraindication due to the perceived risk of intracranial placement.
      The purpose of the present study was to assess the risk of intracranial placement
      in patients with facial fractures who undergo BNTI. The records of 311 patients
      with facial fractures were reviewed for methods of intubation and complications.
      Eighty-two patients underwent BNTI. There were no cases of intracranial
      placement, significant epistaxis requiring nasal packing, esophageal intubation,
      or osteomyelitis. Three patients (4%) developed sinusitis and eight (10%)
      developed aspiration pneumonia. We conclude that the presence of facial trauma
      does not appear to be a contraindication to BNTI.

PMID- 9144053
TI  - The pathophysiology of tension pneumothorax in ventilated swine.
AB  - It remains unclear as to whether the cardiovascular collapse observed in tension
      pneumothorax (TP) is strictly a mechanical pressure-related phenomenon or
      secondary to hypoxemia. This study describes the pathophysiologic changes
      associated with a surgically induced progressive TP in a ventilated swine model.
      With a balloon occlusion catheter surgically placed into the pleural space,
      progressive volumes of pneumothorax were created in six anesthetized pigs on
      positive-pressure ventilation. Air was introduced into the right hemithorax in
      100-mL increments every 4-5 min, with measurements of heart rate (HR), mean
      arterial pressure (MAP), central venous pressure (CVP), mean intrapleural
      pressure (MIP), oxygen saturation (O2%), arterial blood gas (ABG), and cardiac
      output (C.O.). With the induced progressive TP, results showed that O2% measures
      decreased immediately and continued to decline throughout the experiment to
      levels below 50% prior to cardiovascular collapse. The MAP and HR remained
      relatively stable until approximately 57% total lung capacity progressive TP (600
      mL) was reached. At this point, a significant decline in MAP and increase in HR
      was noted, indicating tension physiology. The C.O. showed a small but significant
      decrease after 200 mL of air was injected, with a progressive decline after this
      point. At > 97% total lung capacity TP, lethal cardiovascular collapse occurred
      in all animals and was associated with an abrupt drop in C.O., HR, and MAP. There
      was a concurrent equalization of MIP with CVP at the point of collapse. Arterial
      blood gas measures correlated with O2% trends during the trials. We conclude that
      the findings of this study support the alternative hypothesis that significant
      hypoxemia occurs early and precedes hypotension in ventilated animals with TP.
      Occlusive mechanical compression, suggested by equalization of MIP and CVP, is
      probably a late event.

PMID- 9144054
TI  - Case reports of two patients with pneumothorax following acupuncture.
AB  - We report two patients who presented to the emergency department with
      pneumothorax related to acupuncture. The first patient developed pleuritic chest
      pain and shortness of breath while undergoing acupuncture therapy, and the second
      patient developed similar symptoms 10 min after acupuncture therapy. Neither
      patient had a previous history of pneumothorax, and both were undergoing
      acupuncture along the spine, paraspinal region, and shoulders. A review of the
      literature follows.

PMID- 9144055
TI  - Emergencies in the air: problems, management, and prevention.
AB  - Medical emergencies may arise on board commercial airlines. Although infrequent,
      such events annually affect a substantial number of air travelers. Physicians
      should be aware of the options available to them should they find themselves in
      an emergency situation on an aircraft. This article examines the incidence of in
      flight emergencies, surveys the onboard medical kit, and explores various in
      flight medical problems and treatments. It concludes with a discussion of various
      methods of prevention.

PMID- 9144056
TI  - Hematoma of the rectus abdominis muscle: case report and review of the
      literature.
AB  - Hematoma of the rectus abdominis muscle, although a well-described clinical
      entity, is commonly misdiagnosed. A case of abdominal pain associated with the
      subjective perception of a "lump," which proved to be a rectus abdominis
      hematoma, is presented. The pathoanatomy, presenting symptoms, investigation, and
      treatment options for the condition are reviewed.

PMID- 9144057
TI  - Trauma management in solid organ transplant recipients.
AB  - With trauma being common in this country and over 110,000 recent organ
      transplants performed, transplant recipients may become trauma victims. At
      present, only a few older small series of traumatized transplant patients exist.
      At the University of Arkansas, over the past 40 months, 12 patients with
      significant trauma were retrospectively identified (seven with kidney and five
      with combined kidney and pancreas transplants). The most common causes of trauma
      were car accidents and falls. All patients suffered closed skeletal fractures,
      and no transplanted organs were directly injured or lost. Complications included
      death, deep vein thrombosis, renal failure, sepsis, and pneumonia. In spite of
      immunosuppression and preexisting renal osteodystrophy, fractures in the
      surviving patients healed, with a mean follow-up of 15 months. A large series of
      traumatized transplant patients is presented with a review of the management of
      traumatic injuries for each type of organ transplant. A trauma transplant
      registry is needed to formulate appropriate management and follow-up.

PMID- 9144058
TI  - Medical management of ectopic pregnancy--the role of methotrexate.
AB  - Ectopic pregnancy is an increasing health risk for women throughout the world.
      Recent advances in measurements of serum quantitative beta human chorionic
      gonadotropin and transvaginal ultrasonography have made it possible to diagnose
      ectopic pregnancy without laparoscopy. These developments have provided the
      atmosphere for trials using methotrexate as a nonsurgical treatment for ectopic
      pregnancy. This article briefly reviews the epidemiology and diagnosis of ectopic
      pregnancy. The medical management of ectopic pregnancy with methotrexate is then
      reviewed in more detail.

PMID- 9144059
TI  - Sodium bicarbonate to correct widened QRS in a case of flecainide overdose.
AB  - A 16-yr-old male attempted suicide by ingesting approximately 4000 mg of
      flecainide. He developed coma, hypotension, and ventricular tachycardia. In
      addition to supportive care and antidysrhythmics, he received intravenous sodium
      bicarbonate for the wide complex dysrhythmia. Animal studies and anecdotal human
      experience have suggested that increasing the extracellular sodium improves
      cardiac conduction in flecainide toxicity. The patient's QRS narrowed immediately
      following sodium bicarbonate infusion. Sodium bicarbonate may be useful in the
      treatment of widened QRS and ventricular ectopy resulting from flecainide
      toxicity.

PMID- 9144061
TI  - Ulnar collateral ligament rupture of the first metacarpophalangeal joint: a
      frequently missed injury in the emergency department.
AB  - Between July 1991 and December 1995, 28 patients elected to consult one of the
      senior authors for a second opinion or were referred to him by their family
      physician after being reassured and discharged from our emergency department with
      the simple diagnosis of "soft tissue contusion" to the thumb. Physical
      examination and stress radiographs of these patients revealed a missed injury to
      the ulnar collateral ligament (UCL) of the first metacarpophalangeal joint in 18
      patients (64.3%), 12 of whom required surgical repair. Apparently, UCL injuries
      are frequently underestimated in our emergency department, although the real
      number is unknown because some patients may have decided to seek further
      treatment elsewhere. In addition to the numerous trivial injuries that are
      frequently seen in any emergency department, emergency physicians have the added
      responsibility of detecting those injuries that require referral to a specialist.

PMID- 9144060
TI  - Intracranial placement of a nasotracheal tube after facial fracture: a rare
      complication.
AB  - Extensive facial trauma is often associated with fractures to the skull base,
      cribriform plate, and sphenoid sinus. Attempted intubation of patients with
      facial trauma may result in intracranial penetration and placement of nasogastric
      or nasotracheal tubes into the brain. Such a complication carries significant
      morbidity and mortality. Intracranial placement of nasogastric tubes has been
      reported multiple times in the literature. Intracranial placement of a
      nasotracheal tube, however, has been reported only twice. Such a case is
      presented, along with a review of the literature and a discussion.

PMID- 9144062
TI  - Transverse bayonet dislocation of the distal interphalangeal joint--a case
      report.
AB  - Transverse bayonet dislocation of an interphalangeal joint is an unstable injury
      caused by the disruption of both collateral ligaments. This injury pattern in
      proximal interphalangeal joint was first described by Patel et al. (Clin Orthop
      Rel Res. 1978;133:219), who coined the term "bayonet dislocation" to describe
      this particular type of injury. The case of a distal interphalangeal transverse
      dislocation is presented. This dislocation was successfully treated by closed
      reduction and immobilization with an aluminum splint and buddy taping to the
      adjacent finger.

PMID- 9144063
TI  - Avulsion fracture of tendon of extensor carpi radialis longus: unknown mechanism.
AB  - Fractures of the base of the second metacarpal are infrequent events compared
      with those of the first or fifth metacarpal. Furthermore, these fractures are
      often difficult to visualize on standard radiographs. There is controversy
      regarding the management of such fractures. Two case reports and a discussion of
      this entity are presented.

PMID- 9144064
TI  - Surgical glove lubricants: from toxicity to opportunity.
AB  - In most emergency departments, surgical gloves are coated with surface powders
      that act as lubricants to facilitate donning. Cornstarch powder is an absorbable
      powder employed as a donning agent on most powdered gloves. Talcum powder, a
      nonabsorbable powder, is used as a mold release agent in glove manufacture and is
      still commonly found on the surfaces of modern surgical gloves. These powders are
      foreign bodies that elicit inflammatory responses, leading to a wide number of
      symptoms and complications. The best method of preventing clinical complications
      from glove powder is to use powder-free gloves.

PMID- 9144065
TI  - A review of etomidate for rapid sequence intubation in the emergency department.
AB  - Currently, there is no one drug that is the agent of choice for induction in
      rapid sequence intubation in the emergency department (ED). All agents currently
      used as induction agents in the ED offer distinct advantages for various clinical
      conditions, but each has a significant side effect profile and specific
      contraindications that limit its use in many common clinical settings. A review
      of the data available from the anesthesia literature suggests that etomidate
      possesses many properties that may make it the agent of choice for rapid sequence
      intubations in the ED. These advantages include excellent pharmacodynamics,
      protection from myocardial and cerebral ischemia, minimal histamine release, and
      a hemodynamic profile that is uniquely stable. Disadvantages include a lack of
      blunting of sympathetic response to intubation, a high incidence of myoclonus,
      prominent nausea and vomiting, potential activation of seizures in patients with
      epileptogenic foci, and impaired glucocorticoid response to stress. Further
      studies are needed to evaluate the advantages and disadvantages of the use of
      etomidate for rapid sequence intubation in the ED.

PMID- 9144066
TI  - A 4-yr-old girl with cardiac arrest after a week of flulike symptoms.

PMID- 9144067
TI  - Wangensteen's transformation of the treatment of intestinal obstruction from
      empiric craft to scientific discipline.
AB  - Dr. Owen Wangensteen, who is considered by many to be the greatest surgical
      educator of the 20th century, is recognized for his revolutionary studies of
      intestinal obstruction. He defined the criteria for the early diagnosis of
      intestinal obstruction with the aid of a stethoscope and X-ray examination.
      Moreover, be discovered that suction through a nasal catheter extended to the
      stomach could relieve the distention by gas as effectively as enterostomy. In his
      innovative studies, Dr. Wangensteen reduced the mortality from intestinal
      obstruction from more than 60% to 5%.

PMID- 9144068
TI  - Blind nasotracheal intubation in the presence of facial trauma--is it safe?

PMID- 9144069
TI  - Emergency department management of pain.

PMID- 9144070
TI  - IV ketorolac for the treatment of ureteral and biliary colic.

PMID- 9144071
TI  - Comment on "Diagnosis and treatment of rotator cuff tears in the emergency
      department".

PMID- 9144072
TI  - International Health Fellowship: a proposed curriculum for emergency physicians.
AB  - There are a growing number of emergency physicians (EPs) working in health care
      abroad. There are, however, no formal training programs for EPs in international
      health. An International Health Fellowship has been developed to provide training
      for EPs in public health and international medicine. The fundamental competencies
      of a fellow completing the International Health Fellowship include assessment of
      medical need, program development, integration of programs into the existing
      health care framework, and evaluation of projects. This article outlines the
      philosophy of a training program in international health, provides an overview of
      the goals and objectives for such a program, and describes the development of an
      existing fellowship. The International Health Fellowship will develop leaders in
      the field of global health by combining clinical expertise, practical field
      experience, formal public health training, and research and education in
      international health. Physicians completing a fellowship will be prepared to work
      within foreign health systems to develop, integrate, and evaluate health care
      programs on an international scale.

PMID- 9144073
TI  - Reactivity of murine and human recombinant LPS-binding protein (LBP) within LPS
      and gram negative bacteria.
AB  - The serum lipopolysaccharide (LPS) binding protein, LBP, has been shown to
      greatly enhance cellular responses to low concentrations of LPS. Purified LBP
      facilitates the transfer of LPS to membrane-bound or soluble CD14; the CD14/LPS
      complex then triggers a signal in responsive cells. We have cloned and sequenced
      a cDNA encoding murine LBP, and produced recombinant murine LBP using a
      baculovirus expression system. Using either a solid-phase or a cytofluorometric
      assay, recombinant murine and human LBP were found to bind avidly to free LPS,
      but only weakly to live bacteria from most LPS-containing Gram negative strains.
      Binding correlated loosely with the length and composition of the polysaccharide
      O chains. However, recombinant LBP did bind well to all heat-killed bacterial
      preparations. These findings suggest that LBP could be implicated in the response
      to killed but not live Gram negative bacteria.

PMID- 9144074
TI  - Contribution of TNF/TNF receptor and of Fas ligand to toxicity in murine models
      of endotoxemia and bacterial peritonitis.
AB  - Fas/Fas ligand and TNF/TNF receptors are involved in apoptosis. Whether both
      systems are involved in septic shock has not been determined so far. We
      investigated the role of TNF/TNFR and Fas/Fas ligand in models of endotoxemia and
      of speticemia in mice. Upon LPS challenge, TNF and TNFR p55 were involved in the
      process inducing lethality. FasL did not contribute to enhance lethality, as
      evidenced in gld mice, lacing FasL. Following an intraperitoneal injection of
      live E. coli, TNF and TNFR p55 were necessary to combat infection. Disruption of
      either gene was associated with enhanced lethality and failure to clear the
      bacteria. No effect observed in gld mice in this peritonitis model. Thus, these
      observations confirmed the pathogenic role of TNF/TNFR in endotoxemia and its
      beneficial role in local bacterial infections. In addition the data ruled out a
      major role for Fas/FasL in septic shock in mice.

PMID- 9144075
TI  - Tumor necrosis factor (TNF)-induced cutaneous necrosis is mediated by TNF
      receptor 1.
AB  - Tumor necrosis factor (TNF) is a central mediator of immune and inflammatory
      responses. Its activities have been shown to be mediated by two distinct
      receptors, TNFR1 (p55) and TNFR2 (p75). The cytoplasmic domains of both TNF
      receptors are unrelated, suggesting that they link to different intracellular
      signaling pathways. To determine their role in vivo in lipopolysaccharide (LPS)-
      and TNF-induced skin inflammatory necrosis, TNFR1-, TNFR2-, and TNF lymphotoxin
      alpha (LT alpha)-deficient mice were used. Skin abscesses were experimentally
      induced with local application of TNF or LPS. Large macroscopic ulcerations were
      observed in TNF-injected wild-type animals and to a slightly lesser extent in
      TNFR2-deficient mice with tissue destruction in both cases extending deep into
      the dermis. Tissue destruction was accompanied by an intense immune infiltrate
      composed mainly of neutrophils, lymphocytes, and macrophages. TNFR1-deficient and
      TNFR1/TNFR2-double-deficient mice, however, did not exhibit any ulceration and
      showed only a very mild inflammatory infiltrate. In TNF/LT alpha-double ligand0
      deficient animals, a moderate epidermal necrosis was observed with a reduced
      inflammatory infiltrate compared to wild-type animals. As with TNF injections,
      subcutaneous injection of LPS induced a comparable pattern of skin necrosis in
      wild-type and TNF receptor mutant mice, yet a slightly more acute inflammatory
      level was observed regardless of the type of animal tested. As found for TNF
      induced skin necrosis, the extent of LPS-induced skin necrosis was reduced in
      TNF/LT alpha-deficient mice compared to wild-type animals. The present data
      strongly suggest that TNFR1, rather than TNFR2, is engaged in LPS- and TNF
      induced skin necrosis and highlight the predominant role played by TNF in LPS
      induced inflammatory diseases.

PMID- 9144076
TI  - Expression of nitric oxide synthase in human peripheral blood mononuclear cells
      and neutrophils.
AB  - It has been clearly demonstrated in rodents that nitric oxide (NO) plays an
      important role in host defense and immunity. However, evidence that human
      leukocytes express inducible nitric oxide synthase (iNOS) or its products has
      been inconclusive and a source of controversy. We report that iNOS could not be
      detected in human monocytes, HL-60 cells, neutrophils, and T cells by Western
      blotting analysis (< or = 10 pg) or by radiolabeled L-arginine-to-L-citrulline
      conversion (< or = 20 pmol L-citrulline) under conditions sufficient to induce
      iNOS in the rodent system and in human hepatocytes, which include activation with
      cytokines, endotoxins, and/or chemoattractants. However, sensitive methods such
      as RT-PCR and Northern blot analysis show "constitutively expressed" iNOS mRNA
      from human monocytes, neutrophils, Jurkat cells, and HL-60 cells. This iNOS mRNA
      is 4.4 kb and is similar to that seen in human hepatocytes and rodent
      macrophages. In spite of the constitutive expression of mRNA in neutrophils and
      the lack of detectable NOS activity (based on Western blotting and L-arginine-to
      L-citrulline conversion assay), stimulation of human neutrophils unit FMLP in
      vitro induced the ADP-ribosylation of an intracellular NO target, glyceraldehyde
      3-PO4 dehydrogenase (GAPDH), in a NO-dependent manner. These studies indicate
      that low levels of NOS protein are expressed in neutrophils (and perhaps T cells
      and monocytes) and produce NO following stimulation. The data indicate that, in
      addition to its phagocytic and tumoricidal activity. NO may also function as an
      autacoid signaling molecule within the cells.

PMID- 9144077
TI  - Crescentic glomerulonephritis in interferon-gamma receptor deficient mice.
AB  - Activation of macrophages by T cells is considered an initiating event in
      glomerular crescent formation. Since interferon-gamma (INF gamma) is a key
      mediator in T-cell-mediated activation of macrophages, we decided to test its
      role in a model of crescentic glomerulonephritis. An anti-glomerular basement
      membrane (GBM) serum was injected intravenously in presensitized wild-type or IFN
      gamma receptor deficient (IFN gamma(R)-/-) mice. Glomerulonephritis with
      glomerular crescents and tubulointerstitial inflammation developed in both
      strains, even though most evaluated morphological parameters and proteinuria
      indicated a less severe pathology in the mutant mice compared to the wild type.
      Thus, IFN gamma is not essential either for glomerular crescent formation or for
      tubulointerstitial involvement in anti-GBM glomerulonephritis in mice. In
      conclusion, the role of macrophages in this model might have been overestimated,
      or other cytokines may compensate for deficient IFN gamma signaling in the
      activation of macrophages.

PMID- 9144078
TI  - Transcellular metabolism of leukotriene A4 by rabbit blood cells: lack of
      relevant LTC4-synthase activity in rabbit platelets.
AB  - The objective of this study was to determine the transcellular metabolism of
      leukotriene A4 by rabbit blood cells. mixed peripheral blood leukocyte
      preparations with and without platelets in a ratio of 1:40 were challenged with
      the Ca(2+)-ionophore A23187. 5-Lipoxygenase metabolites production was assessed
      by RP-HPLC coupled with diode-array UV detection. In light of the observation
      that leukotriene C4 production in leukocyte-platelet coincubation was the same as
      with leukocytes alone, mixed coincubation of human and rabbit blood cells was
      tested. Rabbit leukocytes with human platelets resulted in a significant increase
      of leukotriene C4 production, while no changes were observed in human leukocytes
      with or without rabbit platelets. In agreement with these results, intact rabbit
      platelets or rabbit platelet lysates, unlike human platelets, were not able to
      convert synthetic leukotriene A4 free acid to leukotriene C4. These data provide
      evidence that rabbit leukocytes are able to make a significant amount of
      leukotriene A4 available for transcellular metabolism, while rabbit platelets,
      unlike human platelets, lack leukotriene C4-synthase activity.

PMID- 9144079
TI  - Evolution of mammalian apolipoprotein A-I and conservation of antigenicity:
      correlation with primary and secondary structure.
AB  - We have evaluated the immunoreactivity of 20 monoclonal antibodies (mAbs)
      directed against human apolipoprotein (apo)A-I with a panel of high density
      lipoproteins (HDL) from 13 mammalian species. The pattern of cross-reactivity
      showed that 20 mAbs had different specificity. While not all mAbs recognized apoA
      I from all of the different species, the antigenicity of some sequences was well
      conserved. Thus, mAb A05 cross-reacted with all species except guinea pig and
      rat. In contrast, the mAb 4H1, which recognized residues 2-8, required a specific
      proline in position 3, as no immunoreactivity was found in the species missing
      this amino acid. Furthermore, the presence of a threonine residue in place of
      serine (in position 6) in the cynomolgus monkey was associated with a 20-fold
      loss of immunoreactivity in radioimmunometric assay with 4H1. As most of the
      epitopes were found in CNBr fragments 2 and 3, we sequenced these regions in four
      species (horse, goat, sheep, and cat) and analyzed the alignment of most known
      sequences to evaluate their consensus. Except for the rat and the chicken,
      considerable identity was observed. This permitted us to deduce the involvement
      of the residues in some antigenic epitopes. In the middle of apoA-I, a
      conservative mutation Asp103-->Glu was found sufficient to eliminate all
      reactivity of this epitope for A11 (residues 99-105 ... 12l6-132) in five species
      (rabbit, cow, goat, sheep, and rat). The residues essential to the expression of
      two other epitopes overlapping with A11 were also characterized. Edmundson-wheel
      representation of 18-residue repeated sequences of the different apoA-I species
      (for the eight amphipatic helices of residues 46-63, 68-85, 101-118, 123-140, 143
      160, 167-184, 189-206, and 222-239) showed that secondary structure of apoA-I was
      more conserved than the antigenic epitopes. The N-terminal region, residues 1 to
      about 98, is rich in both strictly preserved sequences and epitope expression in
      most of the species surveyed. This evolutionary conservation of the N-terminal
      domain suggests an important yet unknown function.

PMID- 9144080
TI  - Storage of vitamin A in extrahepatic stellate cells in normal rats.
AB  - In mammals, vitamin A is primarily stored as retinyl esters in hepatic stellate
      cells under normal dietary intake of the vitamin. Previously, extrahepatic
      vitamin A-storing stellate cells have only been identified in animals maintained
      on a vitamin A-rich diet, and it has not been known whether these cells play a
      role in normal vitamin A metabolism. The purpose of this study was, to quantify
      the stellate cell lipid droplet area in hepatic and extrahepatic stellate cells
      in control rats and in rats fed excess vitamin A. The stellate cells were
      identified by the gold chloride staining technique, specific autofluorescence of
      retinyl ester, and by electron microscopy. The stellate cell lipid droplet area
      was then quantitated by the use of morphometric quantitation. We demonstrated
      that lipid droplet-containing stellate cells were identified in liver, lung,
      kidney, and intestine, in normal as well as vitamin A-fed rats. The area of lipid
      droplets in liver, lung, and intestine stellate cells of normal rats was 0.2,
      0.3, and 0.04 mm2 per cm2 tissue, respectively. When the rats were administered
      excess vitamin A, the hepatic, lung, and intestinal stellate cell lipid droplet
      area increased about 10-fold, 2-fold, and 40-fold, respectively. Thus the present
      study shows that extrahepatic stellate cells in lung and intestine of normal rats
      contain lipid droplets, and that these lipid droplets increase in area when high
      doses of vitamin A are fed to the animals. These data suggest that not only liver
      stellate cells but also extrahepatic stellate cells play an important role in
      vitamin A storage in normal as well as vitamin A-fed animals.

PMID- 9144081
TI  - Cryo-electron microscopy of low density lipoprotein and reconstituted discoidal
      high density lipoprotein: imaging of the apolipoprotein moiety.
AB  - Cryo-electron microscopy was used to analyze the structure of low density
      lipoprotein from normolipidemic subjects (N-LDL), phospholipid-depleted N-LDL (PD
      LDL), small dense LDL from hypertriglyceridemic subjects (SD-LDL), and
      reconstituted discoidal high density lipoproteins (rHDL). In different
      projections of N-LDL, a high density component of the particle was visible as two
      parallel bands or as a single ring. Projections of PD-LDL were very similar to
      those of N-LDL, indicating that the contribution of phospholipid headgroups to
      the observed high density structure is minor. In preparations of SD-LDL,
      projections with two high density bands or a single high density ring were rare.
      Instead, triangular and diamond-shaped projections were recognized. In different
      projections of discoidal rHDL, a high density component was visible as a single
      band or as a single ring. The present results indicate that cryo-electron
      microscopy reveals the distribution of apolipoproteins within lipoprotein
      particles. Thus, apolipoprotein B-100 (apoB) in N-LDL appears to be organized as
      a double ring around the particle, while apoB in SD-LDL is indicated to have a
      different conformation. Cryo-electron micrographs of rHDL are consistent with the
      presence of apolipoprotein A-I on the periphery of the lipoprotein disc.

PMID- 9144082
TI  - Biosynthesis of plasmenylethanolamine (1-O-alk-1'-enyl-2-acyl-sn-glycero-3
      phosphoethanolamine) in the guinea pig heart.
AB  - In this study, the isolated guinea pig heart was pulse-labeled with a precursor
      of ethanolamine glycerophospholipid, and then chased with the non-radioactive
      compound for 0-8 h. Labeling with hexadecanol revealed that plasmanylethanolamine
      was the immediate precursor of plasmenylethanolamine, but a substantial portion
      of the label was also found in phosphatidylethanolamine. When ethanolamine was
      used as the precursor, the labeling of plasmenylethanolamine was between 50-65%
      of the labeling of phosphatidylethanolamine, and this ratio was maintained
      throughout the perfusion. The ratio of labeling is similar to the ratio of pool
      sizes of these ethanolamine glycerophospholipid in the heart, which implies that
      the CDP-ethanolamine pathway is also important for plasmenylethanolamine
      biosynthesis. The role of diradylglycerol in the synthesis of each ethanolamine
      glycerophospholipid was also investigated. The ratio of 1-alkenyl-2-acyl glycerol
      to total diradylglycerol content was 7% in the homogenate and 32% in the
      microsomes. However, ethanolamine phosphotransferase displayed a distinct
      selectivity towards 1-alkenyl-2-acyl glycerol. Kinetic studies revealed that the
      synthesis of phosphatidylethanolamine was inhibited by 1-alkenyl-2-acyl glycerol,
      but the formation of plasmenylethanolamine was not affected by 1,2
      diacylglycerol. In addition, the inhibition of ethanolamine phosphotransferase by
      1-alkyl-2-acyl glycerol appears to be an important mechanism for the coordination
      of plasmenylethanolamine biosynthesis via the desaturase reaction and the CDP
      ethanolamine pathway.

PMID- 9144083
TI  - Age-related changes in phospholipid fatty acid composition and monoaminergic
      neurotransmission in the hippocampus of rats fed a balanced or an n-3
      polyunsaturated fatty acid-deficient diet.
AB  - The influence of aging (2, 6, 12, and 24 months) on hippocampal lipid composition
      and neurochemical markers (endogenous noradrenaline, serotonin levels, monoamine
      oxidase (MOA) activities) was studied in rats fed a control or an n-3
      polyunsaturated fatty acid (PUFA)-deficient diet. The n-3 PUFA deficiency reduced
      the 22:6 (n-3) level, compensated by the increase in 22:5 (n-6). However, the
      difference in 22:6 (n-3) content between control and deficient rats was less
      between 2 and 12 months and then became stable. There was an overall age-induced
      decrease in the major phospholipid classes phosphatidylethanolamine (PE), and
      phosphatidylcholine (PC) whereas the minor classes, phosphatidylinositol (PI),
      phosphatidylserine (PS), and sphingomyelin (SM), were greatly increased,
      regardless of diet. The n-3 PUFA deficiency induced a reduction in the PS level,
      concomitant with a higher level in MAO-B activity as compared to control rats at
      the age of 24 months. The age-related evolution of the MAO-B activity was
      parallel with that of noradrenaline levels in both dietary groups. The
      noradrenaline and serotonin levels were modified according to age but without
      effect of the n-3 PUFA deficiency. Results showed that the hippocampus sustained
      specific age-induced modifications in lipid composition and neurotransmission
      factors, often with a transition period between 6 and 12 months.

PMID- 9144084
TI  - Charge properties of low density lipoprotein subclasses.
AB  - Measurements of electrophoretic mobility and particle size of low density
      lipoproteins (LDL) allowed use of standard electrokinetic theory to quantitate
      LDL charge characteristics from subjects with predominance of large LDL (pattern
      A, n = 9) or small LDL (pattern B, n = 8). Pattern A LDL was found to have
      significantly lower (P < or = 0.001) mobility (-0.22 +/- 0.01 micron s-1 cm V-1),
      surface potential (-4.2 +/- 0.3 mV) and charge density (-500 +/- 34 esu/cm2) than
      pattern B LDL (-0.25 +/- 0.01 micron s-1 cm V-1, -4.9 +/- 0.3 mV, and -580 +/- 30
      esu/cm2), but no significant difference in particle valence (-22.0 +/- 1.4 for
      pattern A vs. -21.8 +/- 1.9 for pattern B). Thus, the greater mobility of pattern
      B LDL is due to similar net charge residing on a smaller particle. Comparison of
      subfractions in pattern B relative to pattern A LDL revealed greater surface
      potential in all pattern B subfractions and greater charge density in fractions
      of d > or = 1.032 g/ml. In a subset of subjects incubation with neuraminidase
      produced significant reductions in all LDL charge parameters for all
      subfractions, but did not abolish the differences between pattern A and B. Thus
      increased surface potential and charge density of unfractionated pattern B LDL is
      due both to charge properties of particles across the size and density spectrum
      as well as enrichment of pattern B LDL with smaller, denser particles that have
      higher surface charge density.

PMID- 9144085
TI  - Sepsis-induced regulation of lipoprotein lipase expression in rat adipose tissue
      and soleus muscle.
AB  - Hypertriglyceridemia of sepsis is associated with suppressed tissue lipoprotein
      lipase (LPL) activities. We investigated the effect of sepsis on lipoprotein
      lipase gene expression in epididymal fat and soleus muscle from control and
      septic rats in the fasted and fed state. After 24 h of sepsis, LPL activity
      decreased significantly in epididymal fat from fasted rats by 45% along with a
      57% reduction in LPL mRNA levels and LPL mass. Transcription rate, measured by
      nuclear run-on assay, decreased by 70% in epididymal fat from fasted septic rats
      compared to fasted control rats. The synthesis rate of LPL in epididymal fat
      decreased by 31% while the LPL relative synthesis declined by 50% during sepsis.
      The turnover rate was not altered. Sepsis in fed rats did not lead to a
      significant decrease in LPL mRNA in epididymal fat but did lower LPL activity and
      LPL mass by 45%. The sepsis-induced suppression in soleus LPL activity, LPL mRNA
      levels, and LPL mass in the fasted state also was observed when septic rats were
      fed. The results indicate that during fasting sepsis, LPL expression in
      epididymal fat and possibly soleus muscle involves transcriptional regulation.
      During sepsis in the fed state, the regulation of LPL in adipose tissue may
      involve posttranslational mechanisms.

PMID- 9144086
TI  - Decreased phosphatidylcholine biosynthesis and abnormal distribution of
      CTP:phosphocholine cytidylyltransferase in cholesterol auxotrophic Chinese
      hamster ovary cells.
AB  - Phosphatidylcholine (PtdCho) biosynthesis was examined in the sterol regulatory
      defective (SRD) Chinese hamster ovary (CHO) cell line SRD 6. SRD 6 cells do not
      display transcriptional activation of sterol-regulated genes and are cholesterol
      auxotrophs. Compared to CHO 7 cells (parental line from which the SRD cells were
      derived), incorporation of [3H]choline during a 2-h pulse into PtdCho and
      sphingomyelin was reduced 3- and 4.5-fold, respectively, in SRD 6 cells grown
      with or without cholesterol. SRD 6 cells grown in cholesterol-free medium for 24
      h had 8% less phosphatidylcholine (PtdCho) mass compared to CHO 7 cells.
      Consistent with impaired CTP:phosphocholine cytidylyltransferase activity,
      [3H]choline-labeled SRD 6 cells had elevated [3H]phosphocholine and delayed
      conversion to [3H]PtdCho during a 2-h chase period. Compared to CHO 7 cells,
      cytosolic cytidylyltransferase activity was elevated 2- to 3-fold in SRD 6 cells
      grown in the absence of cholesterol, but activity in the total membrane fraction
      was normal. Immunoblot analysis confirmed that cytidylyltransferase mass was
      increased 2-fold in SRD 6 total cell extracts and cytosol, but not membranes. The
      amount of [32P]phosphate-labeled cytidylyltransferase in cytosol and membranes of
      SRD 6 cells were similar to controls. Likewise, cytidylyltransferase mRNA levels
      were not significantly different between SRD 6 and CHO 7. The defect in PtdCho
      synthesis in SRD 6 cells could be overcome by treatment with 150 microns oleate,
      such that after 5 h [3H] choline incorporation into PtdCho and phosphocholine in
      SRD 6 and CHO 7 cells was similar. Cholesterol auxotrophic SRD 6 cells display
      reduced PtdCho mass and synthesis and elevated levels of cytosolic
      cytidylyltransferase, defects that were only partially corrected by growth in
      exogenous cholesterol. These results indicate a requirement for normal
      cholesterol regulation and synthesis in the maintenance PtdCho levels and
      activity of cytidylyltransferase.

PMID- 9144087
TI  - Sources of cholesterol during development of the rat fetus and fetal organs.
AB  - Female rats at various stages of pregnancy were injected intraperitoneally with
      [3H]water; 4 h later, they were killed, the uterus was removed, and the fetuses
      were dissected. Lipids were isolated and fractionated by HPLC and the total
      amount of cholesterol in each organ, as well as radioactivity incorporated into
      cholesterol and cholesterol precursors, were determined. From the data for
      cholesterol content at each age we calculated the rate of accumulation of
      cholesterol during fetal development. As incorporation of label from [3H]water
      takes place with a stoichiometry defined by a known biosynthetic pathway, we were
      also able to determine the fraction of cholesterol accumulating in each organ
      that had been newly synthesized. For the fetus as a whole, more than 93% of the
      cholesterol accumulating during development was newly synthesized. As the
      specific radioactivity of cholesterol in the maternal circulation was negligible
      (because synthesis of cholesterol by maternal liver was suppressed by inclusion
      of cholesterol in the diet), we conclude that the fetus synthesizes nearly all of
      its own cholesterol; neither the maternal circulation nor the placenta/yolk sac
      contribute significant amounts of cholesterol to the fetus. We were also able to
      quantitate trafficking of cholesterol between fetal organs. Fetal brain is
      responsible for the synthesis of all of its own cholesterol. In contrast, fetal
      liver exports cholesterol into the fetal circulation and supplies about half of
      the cholesterol for development of heart, lung, and kidney.

PMID- 9144088
TI  - Modification of the cholesterol efflux properties of human serum by enrichment
      with phospholipid.
AB  - To investigate the importance of phospholipid in promoting cholesterol efflux
      from cells, phospholipid multilamellar vesicles were incubated with normal human
      serum and the efflux ability of these lipid-modified sera was tested. When
      incubated under appropriate conditions, both dimyristoylphosphatidylcholine
      (DMPC) and bovine brain sphingomyelin (BBSM) were shown to combine with
      components of human serum to form new protein:lipid complexes and to markedly
      enhance the ability of serum to promote efflux of cholesterol from Fu5AH cells.
      In particular, the high density lipoprotein (HDL) particles were altered in their
      composition and electrophoretic properties and the alpha-migrating species, which
      were reactive with antibodies to apo-A-I, were converted to larger, pre-beta
      migrating particles, similar in electrophoretic properties to pre beta(2)-HDL.
      DMPC, but not BBSM, also generated particles with mobility similar to pre beta(2)
      HDL; These species were demonstrably different from the discoidal complexes
      formed by reaction of DMPC with purified apoA-I. However, no change in
      cholesterol efflux potential was observed when serum was mixed with phospholipids
      that failed to interact or when cells were incubated with phospholipid
      multilamellar vesicles alone. To further identify the components of serum that
      become altered in their efflux potential after reaction with phospholipid,
      isolated lipoprotein fractions were incubated with DMPC or BBSM and it was found
      that only interaction with HDL caused enhancement of cholesterol efflux. In
      summary, cholesterol removal from the Fu5AH cells by serum can be promoted by
      adding phospholipid under conditions where new HDL-like complexes can be formed
      between the phospholipid and serum components, most notably apolipoprotein A-I.

PMID- 9144089
TI  - Uptake and metabolism of palmitate by isolated cardiac myocytes from adult rats:
      involvement of sarcolemmal proteins.
AB  - The precise mechanism of uptake of long-chain fatty acids (FA) by cardiac
      myocytes is incompletely understood. We examined the involvement of sarcolemmal
      proteins in the initial uptake of FA by isolated rat cardiac myocytes, and the
      relation between initial uptake and metabolism. Cardiac myocytes were incubated
      in the presence of 90 microns [1-14C]palmitate complexed to 300 microns bovine
      serum albumin (BSA), presenting a physiologically relevant condition. During
      initial palmitate uptake (3 min), 56% of the intracellularly sequestered
      palmitate was esterified, and an additional 21% converted into oxidation
      intermediates. Varying the palmitate/BSA molar ratio revealed saturation kinetics
      with the apparent Km for cellular palmitate uptake (435 micro M) to be comparable
      to those for esterification (465 micro M) and oxidation (222 micro M). Varying
      the BSA concentration at a fixed palmitate/BSA molar ratio also showed saturation
      of uptake at increasing concentrations, with an apparent Km for BSA of 23 micro
      M. Changes in palmitate metabolism induced by changes in glucose utilization were
      accompanied by identical effects on palmitate uptake. Addition of lactate also
      inhibited both oxidation and uptake of palmitate, but had no effect on
      esterification. Virtually complete inhibition of palmitate oxidation by etomoxir
      inhibited palmitate uptake for 50%, while decreasing esterification by 33%. In
      the presence of phloretin and trypsin, palmitate uptake and metabolism were
      inhibited 76-88%, and in the presence of sulfo-N-succinimidyloleate by 53%. It is
      concluded that a) the bulk of sarcolemmal palmitate translocation occurs by
      membrane-associated FA-binding proteins, most likely assisted by albumin binding
      proteins without regulatory function, and b) palmitate uptake is most likely
      driven by its rapid intracellular metabolic conversion.

PMID- 9144090
TI  - Apoprotein E phenotype determines serum cholesterol in infants during both high
      cholesterol breast feeding and low-cholesterol formula feeding.
AB  - Our objective was to establish the role of the apoprotein (apo) E phenotype in
      determining serum cholesterol levels in infants fed exclusively on high-fat, high
      cholesterol human milk and in those fed a low-cholesterol, high-unsaturated fat
      formula. The total and lipoprotein cholesterol, apoB, and triglyceride
      concentrations in serum were quantified and related to the apoE phenotype in 151
      infants at birth and at 2, 6, 9, and 12 months of age. Forty-four had the E3/4 or
      4/4 phenotype (E4 group), 94 had the E3/3 phenotype (E3 group), and 13 had the
      E2/3 or 2/4 phenotype (E2 group). In cord blood, cholesterol concentrations
      tended to be higher in the E4 than in the E2 group. With exclusive breast
      feeding, the concentrations rose significantly faster and higher in the E4 group
      than in the E3 group or, especially, the E2 group. The values (mmol/L, mean +/-
      SEM) were 1.6 +/- 0.15, 1.5 +/- 0.05, 1.4 +/- 0.1 (P = n.s.) at birth; 4.2 +/-
      0.1, 3.8 +/- 0.08, 3.4 +/- 0.2 (P < 0.001) at 2 months; 4.4 +/- 0.15, 3.9 +/-
      0.1, 3.4 +/- 0.15 (P < 0.001) at 4 months; 4.3 +/- 0.17, 4.0 +/- 0.13, 3.7 +/-
      0.26 (P < 0.001) at 6 months; 4.8 +/- 0.28, 4.4 +/- 0.11, 3.8 +/- 0.05 (P <
      0.001) at 9 months; and 4.7 +/- 0.11, 4.4 +/- 0.08, 4.1 +/- 0.19 (P < 0.001) at
      12 months, for the E4, E3, and E2 groups, respectively. Increases in LDL
      cholesterol and LDL apoB behaved similarly. The total triglyceride, and total
      HDL, HDL2, and HDL3 cholesterol concentrations did not depend on the apoE
      phenotype. Among infants fed high-fat, high-cholesterol human milk, the total and
      LDL-cholesterol concentrations and the LDL apoB concentration of those with the
      apoE phenotype 4/4 or 3/4 rose faster and to higher levels than in other infants.
      Among formula-fed infants, receiving a low-cholesterol, high-unsaturated fat
      diet, the differences between the apoE groups were smaller.

PMID- 9144092
TI  - 13C-NMR and mass spectral data of steroids with a 17,17-dialkyl-18-nor-13(14)-ene
      substructure.
AB  - We present carbon-13 nuclear magnetic resonance (13C-NMR) and mass spectral data
      for several androstanes and estranes having a 17,17-dialkyl-18-nor-13(14)-ene
      substructure. These compounds are formed by a Wagner-Meerwein rearrangement of
      steroids bearing a tertiary 17-hydroxy group during the derivatization reaction
      with heptafluorobutyric anhydride. The 13C-NMR assignments are compared with
      those of natural products having a similar substructure. The mass spectra show
      characteristic fragment ions for which a fragmentation mechanism is proposed.

PMID- 9144091
TI  - Heparan sulfate proteoglycans mediate internalization and degradation of beta
      VLDL and promote cholesterol accumulation by pigeon macrophages.
AB  - Pigeon and rabbit beta-migrating very low density lipoprotein (beta-VLDL) are
      similar in size and composition, yet rabbit beta-VLDL consistently stimulates
      greater cholesteryl ester accumulation in pigeon peritoneal macrophages than does
      pigeon beta-VLDL. The purpose of this study was to determine the mechanism of
      this difference. Pigeon beta-VLDL bound to both a high and low affinity site
      while rabbit beta-VLDL bound primarily to a low affinity site. The high affinity
      site had the characteristics of the LDL receptor. Most rabbit beta-VLDL and some
      pigeon beta-VLDL bound to the low affinity site that was not down-regulated by
      cholesterol loading. beta-VLDL binding to the low affinity site and subsequent
      internalization and degradation were mediated by cell surface heparan sulfate
      proteoglycans (HSPG). Evidence for this includes inhibition of binding and uptake
      by chlorate, which prevents sulfation of proteoglycans, and by treatment with
      heparinase but not chondroitinase ABC. beta-VLDL uptake was stimulated by
      lipoprotein lipase (LpL) and apolipoprotein E (apoE), both known to bind HSPGs.
      Uptake and degradation of beta-VLDL were not mediated by the LDL receptor or the
      alpha(2)MR/LRP. Thus, binding of beta-VLDL to low affinity, high capacity HSPG
      binding sites on pigeon macrophages appears to directly promote internalization
      and degradation and is largely responsible for the greater ability of rabbit beta
      VLDL to stimulate cholesterol accumulation.

PMID- 9144093
TI  - Membrane phospholipids in temperature adaptation of Candida utilis: alterations
      in fatty acid chain length and unsaturation.
AB  - The effect of decreasing environmental temperature on membrane phospholipids
      (PL), the neutral lipid (NL) composition, and their fatty acid profiles was
      studied in exponentially growing Candida utilis from 40 to 10 degrees C, at
      intervals of 5-9 centigrade degrees. According to the results, fatty acid
      unsaturation increased with decreasing growth temperature from 40 to 26-20
      degrees C, due to the increase in PL containing the most unsaturated fatty acid,
      linolenic acid (mp. -11.3 to -12.8 degrees C). Concomitantly, an equal
      (phosphatidylcholine, PC; phosphatidylethanolamine, PE) or more pronounced
      (phosphatidylinositol and phosphatidylserine, PI + PS) decrease occurred in fatty
      acids with lower unsaturation and, consequently, the cellular fatty acid content
      decreased as the temperature was reduced from 40 to 26-20 degrees C. In addition,
      when the temperature decreased within the lower growth temperature range from 26
      20 to 10 degrees C, the fatty acid chain length also shortened in PL, due to the
      increase in palmitoleic acid (mp. 0 degrees C), and equal (PC and PE) or more
      pronounced (PI + PS) decrease in other acids. Concomitantly, triacylglycerols
      accumulated as the temperature decreased from 26-20 to 10 degrees C. Thus, the
      results showed that C. utilis can adapt cellular membranes to decreases in the
      environmental temperature so that fatty acid unsaturation increases down to 26-20
      degrees C, and t temperatures below that the fatty acid chain length also
      shortens.

PMID- 9144094
TI  - Variation in adrenergic regulation of lipolysis between omental and subcutaneous
      adipocytes from obese and non-obese men.
AB  - Regional variations in adipocyte lipolysis between subcutaneous and visceral fat
      may be important for obesity complications. In the present study, we compared
      adrenergic regulation of lipolysis in omental and subcutaneous adipocytes from
      obese (n = 15) and non-obese (n = 14) male subjects. Waist-to-hip ratio, blood
      pressure, plasma insulin, and plasma triglycerides were increased in obesity. No
      regional differences in adrenoceptor lipolytic function were observed in non
      obese subjects with the exception of a slight increase in noradrenaline
      sensitivity in omental adipocytes (P < 0.05), because of increased beta(1)
      adrenoceptor sensitivity (P < 0.05). In the obese subjects, the rate of
      noradrenaline-induced glycerol release was 2-fold higher (P < 0.005) and the
      noradrenaline sensitivity was 3-fold higher (P < 0.05) in omental versus
      subcutaneous adipocytes. These findings were mainly due to a 50-fold increase in
      omental beta(3)-adrenoceptor sensitivity (P < 0.002) and to a smaller 6-fold
      increase in omental beta(1)-adrenoceptor sensitivity (P < 0.02), accompanied by
      increased beta(3)- as well as beta(1)-adrenoceptor lipolytic rates at
      approximately 50% receptor subtype occupancy by the agonist (P < 0.05). In
      conclusion, minor regional differences in adipocyte lipolytic response to
      catecholamines are present in non-obese males. In contrast, catecholamine-induced
      lipolysis is markedly increased in omental as compared to subcutaneous adipocytes
      in obese males, mainly due to an increase in beta(3)-adrenoceptor function of
      visceral fat cells, in combination with a smaller increase in beta(1)
      adrenoceptor function.

PMID- 9144095
TI  - Pure linoleate deficiency in the rat: influence on growth, accumulation of n-6
      polyunsaturates, and [1-14C]linoleate oxidation.
AB  - Essential fatty acid deficiency has been widely studied but the extent to which
      its effects are attributable specifically to deficiency of linoleate as opposed
      to deficiency of all unsaturated fatty acids is unknown. Our objective was to
      evaluate the effect of pure linoleate deficiency on growth as well as changes in
      the metabolism and oxidation of n-6 polyunsaturates. The diets contained 20
      energy % fat blended from 3 energy % pure oleate, 2 energy % linoleate (0.01
      energy % in the linoleate-deficient group), 0.3 energy % pure alpha-linolenate,
      and the balance as palmitate and stearate from fully hydrogenated soybean oil.
      Thirty-five-day-old rats consumed the two diets for 84 days, after which the
      linoleate-deficient rats weighed 15% less than the controls (P < 0.05), had mild
      scaling on the paws, and visible hair loss (in a few rats). Compared with the
      controls, the ratio of eicosatrienoate to arachidonate after 84 days was elevated
      in liver (170-fold) and serum (520-fold) phospholipids of the linoleate-deficient
      group. In total, linoleate-deficient rats consumed 122 mg of linoleate and had a
      net whole body loss of 479 mg n-6 polyunsaturates compared with an intake of
      24,130 mg and a net whole body gain of 7206 mg n-6 polyunsaturates in the control
      group. Linoleate-deficient rats oxidized 1% of an oral bolus of [1-14C]linoleate
      over 8 h compared with 34% in the control rats (P < 0.05). We conclude that pure
      linoleate deficiency has marked effects on accumulation of n-6 polyunsaturates
      but induces milder gross symptoms, particularly growth retardation, than
      classical essential fatty acid deficiency. alpha-Linolenate and possibly oleate
      may have a sparing effect on linoleate oxidation from body stores during
      linoleate deficiency.

PMID- 9144096
TI  - Expression of human lecithin:cholesterol acyltransferase in transgenic mice:
      effects on cholesterol efflux, esterification, and transport.
AB  - Human lecithin:cholesterol acyltransferase (LCAT) is a key enzyme in the plasma
      metabolism of cholesterol and is postulated to participate in a physiologic
      process called reverse cholesterol transport. We have used transgenic mice
      expressing the human LCAT transgene to study the effect of increased plasma
      levels of LCAT in each of the proposed steps involved in the reverse cholesterol
      transport pathway. High density lipoprotein (HDL) from LCAT transgenic mice was
      44% more efficient than control mouse HDL in the efflux of cholesterol from human
      skin fibroblasts. Esterification of cell-derived cholesterol was also markedly
      increased in mice expressing the human LCAT transgene. The rate of plasma
      clearance of HDL cholesteryl ester was virtually the same in both types of
      animals whereas the HDL cholesteryl ester transport rate was significantly
      increased in mice expressing the human LCAT transgene (152.3 +/- 16.9
      micrograms/h vs. 203.1 +/- 30.9 micrograms/h in control and transgenic mice,
      respectively). Liver cholesteryl ester uptake was significantly increased in mice
      expressing human LCAT (58.0 +/- 1.4 micrograms/h/g liver vs. 77.9 +/- 1.7
      micrograms/h/g liver in control and transgenic mice, respectively). These studies
      indicate that LCAT modulates the rate by which cholesterol is effluxed from cell
      membranes onto HDL, esterified, and transported to the liver.

PMID- 9144097
TI  - Spectrophotometric assay for total peroxyl radical-trapping antioxidant potential
      in human serum.
AB  - Antioxidants prevent modification of low density lipoprotein (LDL) by free
      radicals and possibly also atheroma formation. The capacity of human serum to
      resist attacks by free radicals is measured by the total peroxyl radical-trapping
      potential (TRAP). Its measurement has thus far required equipment not available
      in many clinical laboratories such as a thermostated oxygen electrode cell or a
      luminometer. To develop a simpler method we used a free radical probe,
      dichlorofluorescin-diacetate (DCFH-DA), described before in studies of
      respiratory burst in inflammatory cells. Its oxidation by radicals from thermal
      decomposition of 2,2'-diazobis(2-amidinopropane)dihydrochloride (AAPH) converts
      this compound to highly fluorescent dichlorofluorescein (DCF). The DCF also has
      absorbance at 504 nm thus enabling the determination of TRAP either
      fluorometrically or spectrophotometrically. Increasing the concentration of AAPH
      enables the measurement of DCF formation and its inhibition by serum samples at
      room temperature. The intra- and interassay coefficients of variation of this
      assay are 3.4% and 4.6%, respectively. The mean value for serum TRAP of healthy
      subjects is 1155 mumol/l (n = 38). The TRAP in human serum can be increased by
      adding various antioxidant substances to the assay in vitro or by dietary
      supplementation of healthy subjects with vitamin E in vivo (P < 0.025). An
      increase was also found in serum vitamin E levels (P < 0.0001) and in the length
      of the time human LDL is able to resist oxidation (P < 0.05). Thus the
      determination of TRAP by this method, which requires only commercially available
      chemicals, can be used for the evaluation of phenomena associated with lipid
      accumulation in human artery wall.

PMID- 9144098
TI  - Cognitive screening instruments in neuropsychiatry: a report of the Committee on
      Research of the American Neuropsychiatric Association.
AB  - A 1994 survey by the Research Committee of the American Neuropsychiatric
      Association revealed that 58% of respondents employed formal assessment of
      cognitive status; the Mini-Mental State Examination (MMSE) and neuropsychological
      testing were the commonest techniques. Literature review on common cognitive
      screening instruments found that the MMSE has widespread popularity, ease of use,
      and a large body of research demonstrating its sensitivity to common
      neuropsychiatric disorders. The Committee recommends that clinicians who employ
      the MMSE 1) use it as a minimum screening for cognitive dysfunction; 2) employ
      age- and education-normative corrections; and 3) supplement it with specific
      measures of spatial functions, delayed memory, and executive abilities. The
      Modified MMSE and the Neurobehavioral Cognitive Status Examination also show
      promise as screening tools.

PMID- 9144099
TI  - The neuroanatomy of 5-HT dysregulation and panic disorder.
AB  - The advent of highly effective antipanic medications with specific serotonin
      reuptake inhibition as a mechanism of action has prompted the need for new
      pathophysiological models of panic disorder. The authors attempt an integration
      of the emerging basic science literature regarding the neuro-anatomy and
      physiology of the mammalian central serotonin nervous system, its influence on
      neural substrates that underlie fear and defense responses, and the clinical
      literature pertaining to serotonin-related abnormalities in panic disorder. A
      neuro-anatomical model for the potential sites of action of the specific
      serotonin reuptake inhibitors in panic disorder is proposed.

PMID- 9144100
TI  - Recurrence and relapse in geriatric depression: a review of risk factors and
      prophylactic treatment strategies.
AB  - An emerging body of epidemiologic data has substantiated that in younger and
      middle-aged populations, major depression may be characterized by early relapse,
      recurrence, and chronicity. Information regarding the prognosis of geriatric
      depression is less extensive. This article reviews the literature on the
      longitudinal outcome of major depression in older adults, with particular
      emphasis on the limited data on strategies for the pharmacologic and
      electroconvulsive prophylaxis of recurrent unipolar geriatric depression.
      Possible biological markers for relapse risk, derived from sleep
      electroencephalography, neuroendocrine tests, and neuroradiographic findings, are
      also discussed. Recommendations for the treatment and long-term follow-up of
      geriatric depression are presented.

PMID- 9144101
TI  - Effect of amantadine hydrochloride on symptoms of frontal lobe dysfunction in
      brain injury: case studies and review.
AB  - Symptoms consistent with dysfunction of the frontal lobes can occur following
      traumatic brain injury (TBI) or other types of acquired brain injury (stroke,
      aneurysm). These symptoms can include problems with short-term memory, attention,
      planning, problem solving, impulsivity, disinhibition, poor motivation, and other
      behavioral and cognitive deficits ("frontal lobe syndrome"). These symptoms may
      respond to certain drugs, such as dopaminergic agents. This case series describes
      results of using amantadine in 7 patients with this type of symptom profile (6
      with TBI, 1 with meningitis following sinus surgery). Patients received
      neuropsychiatric examinations and serial neuropsychological testing. All patients
      showed some degree of positive response. One had side effects that resolved upon
      discontinuation of drug. The rationale for using dopaminergics is discussed, and
      pertinent literature is reviewed.

PMID- 9144102
TI  - Methylphenidate treatment of negative symptoms in patients with dementia.
AB  - This pilot study evaluated response of negative symptoms (NS) to methylphenidate
      in patients with dementia and relationships between NS, depression, and cognitive
      deficits in these patients. Consecutively admitted patients with NS and dementia-
      12 with dementia of Alzheimer's type and 15 with vascular dementia--were rated on
      severity of NS (SANS and PANSS-N scales), depressive symptoms (Ham-D), and
      cognitive impairment (MMSE) before and after treatment with methylphenidate. NS
      decreased significantly, and cognitive scores increased. A decrease in depression
      scores was nonsignificant after all variance attributable to NS was removed. NS,
      depression, and cognitive scores were not significantly intercorrelated. Results
      were similar for Alzheimer's and vascular dementia patients. Negative symptoms in
      dementia patients appear responsive to methylphenidate treatment. This effect may
      underlie putative changes in symptoms of depression observed by other
      researchers.

PMID- 9144103
TI  - The effects of clozapine on cognitive functioning in treatment-resistant
      schizophrenic patients.
AB  - This study examined the cognitive functioning of 10 treatment-resistant
      schizophrenic patients after a minimum of a 1-year trial on clozapine. Results
      indicated significant improvements on prorated Wechsler Adult Intelligence Scale
      Revised (WAIS-R) Full Scale, Verbal, and Performance IQs and on the WAIS-R
      Similarities and Digit Symbol subtests. A trend was also found for improvement on
      the Wisconsin Card Sorting Test. It was concluded that clozapine treatment is
      associated with global cognitive improvements in patients with treatment
      resistant schizophrenia. Clozapine treatment may also improve performance on the
      Wisconsin Card Sorting Test in a subset of patients. Improvement did not appear
      to be related to the reduction of any cognitive effects of the typical
      neuroleptics upon their discontinuation.

PMID- 9144104
TI  - Psychiatric correlates of MR deep white matter lesions in probable Alzheimer's
      disease.
AB  - The authors examined the relationship between psychiatric symptoms and the
      presence of of MR deep white matter lesions (DWMLs) in 28 probable Alzheimer's
      disease (AD) patients with mild to moderate dementia. The difference in frequency
      of psychiatric symptoms between patients with and without DWMLs was not
      statistically significant. However, MR global scores of severity correlated with
      the presence of ideational disturbances (such as low self-esteem and suicidal
      ideation). Analysis of specific cerebral regions indicated that the highest
      correlation occurred in the frontal white matter. Thus, DWMLs are correlated with
      specific symptoms of depression in AD. Whether DWMLs are etiologically related to
      these symptoms remains to be determined.

PMID- 9144105
TI  - Lack of clinically significant gross structural abnormalities in MRIs of older
      patients with schizophrenia and related psychoses.
AB  - The authors examined the reports of MRI brain studies of 69 patients with DSM-III
      R-diagnosed psychotic disorders (30 early-onset and 24 late-onset schizophrenia
      patients and 15 with other psychoses) and 41 normal comparison subjects.
      Participants' ages ranged from 45 to 87 years. A qualitative rating scheme
      determined type and severity of clinically detectable abnormalities, including
      volume loss, infarcts, lacunae, and white matter hyperintensities. In this
      clinically well-characterized sample, the vast majority of the MRIs were within
      normal limits. There were no significant differences between psychosis patients
      and normal comparison subjects or between early-onset and late-onset
      schizophrenia patients in frequency, type, or severity of gross structural
      abnormalities. The results indicate that late-onset schizophrenia and related
      disorders can exist without clinically significant gross structural abnormalities
      in the brain.

PMID- 9144106
TI  - Clinical, motor, and biological correlates of depressive disorders after focal
      subcortical lesions.
AB  - The authors studied depression after focal subcortical lesions (SCLs) in 45
      highly selected subjects. Secondary major depression (secondary MD) occurred in
      20.0%, depressive disorder NOS (secondary  DDNOS) in 4.4%, and secondary
      dysthymia in 0.0%. secondary MD after SCLs was associated with pallidal lesions
      (88.9%) and dystonia without geste antagonistique; subjects with secondary DDNOS
      had nigrotegmental lesions and parkinsonism. Depressive severity after SCLs
      correlated positively with severity of parkinsonism and dystonia. Pallidal
      lesions disrupting neurotransmitter systems and pallidothalamic and parietal
      input to the frontal lobe may lead to secondary MD, whereas nigrotegmental
      lesions may predispose to secondary MD forme fruste (secondary DDNOS) through
      disruption of mesocortical frontal or nigrostriatal dopamine tracts. Patients
      should be closely followed over several years for depression after such lesions,
      especially when accompanied by parkinsonism or dystonia without geste
      antagonistique.

PMID- 9144107
TI  - Impaired neuropsychological functioning in Tourette's syndrome subjects with co
      occurring obsessive-compulsive and attention deficit symptoms.
AB  - This study examined neuropsychological performance by 92 children with Tourette's
      syndrome (TS) grouped by the presence or absence of obsessive-compulsive and/or
      attention deficit symptoms. The identified groups did not differ with respect to
      age, education, age at onset of TS symptoms, or medication use. After statistical
      control for complex motor symptoms, impaired performance on measures of
      achievement and executive functioning was correlated with obsessive and
      obsessive/attention symptoms, but not with attention symptoms alone. The presence
      of both obsessive and attention symptoms identified children with impairment
      across several tasks. Clinical and functional implications are discussed.

PMID- 9144108
TI  - Manic episodes in two patients treated with interferon alpha.
AB  - The authors report the assessment of 2 patients on interferon alpha (IFN-alpha)
      therapy for chronic myelogenous leukemia who developed manic symptoms long after
      IFN-alpha therapy had been initiated. These cases suggest that chronic IFN-alpha
      therapy may be associated with vulnerability for developing overt psychiatric
      symptoms, particularly in cases where the patient is experiencing psychosocial
      stress, and that the current definition of persistent adverse effects of IFN
      alpha should be broadened to include the occurrence of manic episodes.

PMID- 9144109
TI  - AIDS mania.
AB  - Twenty patients with HIV infection and mania were grouped according to whether
      their first manic episode occurred when CD4 count was < 200 (late onset) or > or
      = 200 (early onset). The late-onset patients were less likely to have personal or
      family histories of mood disorder and more likely to have dementia or cognitive
      slowing. They also exhibited a different manic symptom profile. The different
      sociodemographic and symptom profiles associated with early-onset and late-onset
      mania may reflect differences in pathophysiology.

PMID- 9144110
TI  - Frontal cortical atrophy and negative symptoms in patients with chronic alcohol
      dependence.
AB  - It has been suggested that frontal lobe pathology is associated with negative
      symptoms in patients with chronic alcoholism. In his exploratory study, the
      authors examined 19 chronic alcoholic inpatients on an alcohol treatment unit and
      found a significant relationship between severity of frontal atrophy (as measured
      by CT) and negative symptoms (as measured by the Scale for the Assessment of
      Negative Symptoms).

PMID- 9144111
TI  - Neuropsychiatric considerations in the use of electroconvulsive therapy.
AB  - ECT is an effective and rapidly acting treatment for certain major psychiatric
      disorders, even in patients with neurologic illness. Further, in some cases the
      neurologic illness itself also responds to ECT. Patients with some types of
      neurologic illness may be at increased risk of neurologic or cognitive side
      effects from ECT, but these risks can be lowered by careful pre-ECT evaluation
      and optimal ECT technique.

PMID- 9144112
TI  - Ictal and non-ictal psychiatric disorders in temporal lobe epilepsy. 1951.

PMID- 9144113
TI  - Gabapentin in bipolar disorder.

PMID- 9144114
TI  - Selegiline for the delivery of small doses of amphetamine.

PMID- 9144115
TI  - Corticospinal function in conversion disorder.

PMID- 9144116
TI  - Catatonia due to mixed sedative withdrawal.

PMID- 9144117
TI  - The Shwachman Award of the North American Society for Pediatric Gastroenterology
      and Nutrition. Presentation.

PMID- 9144118
TI  - Comparison of two regimens of feeding and oral electrolyte solutions in infants
      with diarrhea.
AB  - BACKGROUND: Glucose-based oral rehydration solutions (ORS) available in the
      United States do not appear to reduce the severity or duration of diarrhea. The
      use of cereal-derived ORS and cereal-based feedings appears to diminish the
      severity of illness in studies conducted in the developing world. To our
      knowledge, no controlled trials of cereal-derived ORS or cereal-based feedings
      have been performed in the United States. METHODS: We performed a randomized,
      double-blind trial of two ORS feeding regimens in outpatients with diarrhea.
      Patients aged 2-13 months with acute watery diarrhea were enrolled. Subjects
      received standard glucose-based ORS in alternation with soy-based, lactose-free
      infant formula (Group 1) or rice syrup solid containing ORS in alternation with
      rice-based, lactose-free infant formula (Group 2). Subjects were visited at home
      daily to determine the severity of illness and characteristics of the stool.
      RESULTS: After the first 2 days, significantly more Group 1 subjects continued to
      have diarrhea than did Group 2 subjects (median duration of diarrhea 3 vs. 2
      days) as demonstrated by Kaplan-Meier survival curves (p = 0.04). CONCLUSION: We
      conclude that infants fed a regimen consisting of rice syrup solid containing ORS
      and rice formula resolved their diarrhea sooner than did infants fed a regimen of
      standard glucose-based ORS and formula. The relative contributions of ORS and
      formula to this more rapid recovery can be elucidated by further studies.

PMID- 9144119
TI  - Five-year follow-up of high-risk infants with family history of allergy who were
      exclusively breast-fed or fed partial whey hydrolysate, soy, and conventional
      cow's milk formulas.
AB  - BACKGROUND: Allergy is a common cause of illness. The effect of feeding different
      infant formulas on the incidence of atopic disease and food allergy was assessed
      in a prospective randomized double-blind study of high-risk infants with a family
      history of atopy. METHODS: 216 high-risk infants whose mothers had elected not to
      breast-feed were randomized to receive exclusively a partial whey hydrolysate
      formula or a conventional cow's milk formula or a soy formula until 6 months of
      age. Seventy-two high risk infants breast-fed for > or = 4 months were also
      studied. RESULTS: Follow-up until 5 years of age showed a significant lowering in
      the cumulative incidence of atopic disease in the breast-fed (odds ratio 0.422
      [0.200-0.891]) and the whey hydrolysate (odds ratio 0.322 [0.159-0.653) groups,
      compared with the conventional cow's milk group. Soy formula was not effective
      (odds ratio 0.759 [0.384-1.501]). The occurrence of both eczema and asthma was
      lowest in the breast-fed and whey hydrolysate groups and was comparable in the
      cow's milk and soy groups. Similar significant differences were noted in the 18
      60 month period prevalence of eczema and asthma. Eczema was less severe in the
      whey hydrolysate group compared with the other groups. Double-blind placebo
      controlled food challenges showed a lower prevalence of food allergy in the whey
      hydrolysate group compared with the other formula groups. CONCLUSIONS: Exclusive
      breast-feeding or feeding with a partial whey hydrolysate formula is associated
      with lower incidence of atopic disease and food allergy. This is a cost-effective
      approach to the prevention of allergic disease in children.

PMID- 9144120
TI  - Fasting gastric fluid and fecal polyamine concentrations in premature infants.
AB  - BACKGROUND: The role of milk polyamines in the development of the
      gastrointestinal tract of human infants is presently unknown. Polyamine
      concentrations are higher in human milk than in infant formulas. The aim of the
      present study was to gather data on luminal polyamines by measuring gastric fluid
      and fecal polyamine concentrations in premature infants during the postnatal
      period. We further compared gastric fluid polyamine concentrations with those
      reported for milk and looked for possible relationships between luminal polyamine
      concentrations, age, and growth rate. METHODS: High-performance liquid
      chromatography was used for the measurement of polyamine concentrations in both
      fecal and gastric fluid samples. RESULTS: Ninetieth centiles for gastric
      polyamines during the first week were 62, 28, 82, and 14 microM for putrescine,
      spermidine, spermine, and cadaverine, respectively. These values are higher than
      those reported for human milk and infant formulas. Polyamine concentrations were
      unrelated to either age or growth rate. Ninetieth centiles for fecal polyamines
      during the first week were 7668, 5176, 53, and 75 microM for cadaverine,
      putrescine, spermidine, and spermine, respectively. CONCLUSIONS: Fasting gastric
      fluid polyamine concentrations in premature infants are higher than those
      reported for either human milk or infant formulas. The high fecal cadaverine and
      putrescine concentrations are probably of bacterial origin.

PMID- 9144121
TI  - Effects of exogenous neurotensin on intestinal postresectional growth in the
      suckling rat.
AB  - BACKGROUND: In the suckling rat, massive bowel resection provokes intestinal
      malabsorption that leads to diminished growth. The object of this report was to
      test whether neurotensin, intestinal trophic peptide, enhances postresection
      intestinal adaptation, improving absorption and reducing the adverse effects of
      resection on growth. METHODS: Fifty-seven 15-day-old suckling. Wistar rats were
      divided into four groups: 41 rats were subjected to resection of 90% of their
      small bowel, while the rest (n = 16) underwent laparotomy. Half of the animals,
      resected and laparotomized, were treated with neurotensin for 30 days. The body
      weight was monitored, and samples of bone and intestinal mucosa were obtained at
      the end of the study period for analysis. Blood was tested to determine iron,
      ferritin, folic acid, and vitamin B12 levels. RESULTS: The resected animals lost
      body weight regardless of neurotensin administration. In the resected animals,
      femur weight increased significantly when they received neurotensin. Bowel
      resection provokes significant increases in the intestinal mucosa (crypts and
      villi), but after neurotensin administration, significant increases were detected
      only in the jejunum of the resected animals but not in the ileum of laparotomized
      rats. In the resected animals, significant decreases in iron, ferritin, folic
      acid, and vitamin B12 levels were observed. The postresection administration of
      neurotensin only produced a significant rise in the ferritin concentration.
      CONCLUSIONS: In the suckling rat, neurotensin enhances the intestinal
      proliferative phenomenon but does not improve the course of medium-term
      postresection growth.

PMID- 9144122
TI  - Lactobacillus reuteri as a therapeutic agent in acute diarrhea in young children.
AB  - BACKGROUND: Certain strains of lactobacilli may promote recovery from acute
      diarrhea. Lactobacillus reuteri is of human origin and is a natural colonizer of
      gastrointestinal tract. In this trial, exogenously administered L. reuteri was
      studied as a therapeutic agent in acute diarrhea. METHODS: Forty patients between
      6 and 36 months of age hospitalized with acute diarrhea (75% rotavirus) were
      studied. After parental consent, the patients were randomized to one of two
      treatment groups to receive either 10(10) to 10(11) colony-forming units of L.
      reuteri or a matching placebo daily for the length of hospitalization or up to 5
      days. The clinical outcome of diarrhea and colonization of L. reuteri were
      evaluated. RESULTS: The mean (SD) duration of watery diarrhea after treatment was
      1.7 (1.6) days in the L. reuteri group and 2.9 (2.3) days in the placebo group (p
      = 0.07). On the second day of treatment only 26% of patients receiving L. reuteri
      had watery diarrhea, compared with 81% of those receiving placebo (p = 0.0005).
      Cultures of lactobacilli from stool samples demonstrated that administration of
      L. reuteri resulted in colonization of the gastrointestinal tract. Lactobacillus
      reuteri accounted for > 75% of the total lactobacilli found in children fed with
      this product. CONCLUSIONS: Lactobacillus reuteri is effective as a therapeutic
      agent in acute rotavirus diarrhea in children. Further studies are warranted to
      confirm the present finding and to explore the full therapeutic potential of L.
      reuteri in acute viral diarrhea.

PMID- 9144123
TI  - A critical analysis of total sialic acid and sialoglycoconjugate contents of
      bovine milk-based infant formulas.
AB  - BACKGROUND: Several infant formulas were bovine milk-based products. Mature
      bovine milk has a very low sialoglycoconjugate content compared with human milk
      from the first phases of lactation. METHODS: The present study was undertaken to
      determine total sialic acid and oligosaccharide, glycoprotein, and ganglioside
      sialic acid contents of bovine milk-based formulas. RESULTS: Starter formulas,
      designed for the first days/weeks after birth, have very similar sialic acid
      contents (233-266 mg/L fresh milk). We found more oligosaccharide-bound sialic
      acids (167-174 mg/L fresh milk) than those bound to proteins (53-84 mg/L fresh
      milk) in these formulas. The ganglioside sialic acid contents of starter formulas
      (952-1135 micrograms/L fresh milk) vary slightly from formula to formula.
      However, all the above-mentioned contents are lower than in human colostrum or
      transitional milk. CONCLUSIONS: Infants fed starter formulas have total sialic
      acid and oligosaccharide, glycoprotein, and ganglioside sialic acid intakes of
      36, 28, 50, and 20%, respectively, of those fed human colostrum or transitional
      milk. By contrast, follow-on formulas, used from 4 to 5 months of age, provide
      total sialic acid and oligosaccharide, glycoprotein, and ganglioside sialic acid
      contents similar to those furnished by mature human milk. Since the reference
      standard for optimal nutrition in the early months of infancy is human milk, a
      supplementation with sialic acid-containing glycoconjugates of infant formulas
      recommended for the first days after delivery could be advisable when breast
      feeding is not possible.

PMID- 9144124
TI  - Antroduodenal motor effects of intravenous erythromycin in children with
      abnormalities of gastrointestinal motility.
AB  - BACKGROUND: The macrolide antibiotic erythromycin (EM) affects gastrointestinal
      motor activity by acting as agonist of motilin receptors located on the smooth
      muscle cells of the gastroduodenal tract. We studied the effect of intravenous EM
      on fasting antroduodenal motility in controls and children with gastrointestinal
      dysmotility. METHODS: EM lactobionate (rate, 3.0 mg/kg/h) was infused
      intravenously while antroduodenal manometry was recorded in 10 controls, in 7
      patients with functional dyspepsia and in 6 patients with gut pseudo-obstruction.
      The mean (SD) age (years) was 5.7 (1.4), 6.5 (2.4), and 6.7 (3.2), respectively.
      Manometry was performed by means of a four- or six-lumen catheter introduced
      through the nose and perfused with a low compliance pneumohydraulic system. Five
      controls received EM and five received saline. RESULTS: EM, infused 5 minutes
      after passage of an activity front (AF), induced in controls a premature
      antroduodenal AF occurring 15.4 +/- 3.2 minutes after starting infusion; no motor
      changes were seen after saline; duration and propagation velocity of EM-induced
      AFs did not differ from spontaneous AFs. In patients with functional dyspepsia EM
      induced various patterns such as premature antroduodenal AFs, antral phase III
      like pattern with short duodenal bursts or prolonged phasic antral waves and no
      duodenal activity. In patients with neurogenic pseudo-obstruction rare or absent
      antral activity with incoordinated or absent duodenal activity was induced; no
      contractions were elicited in two patients with myogenic pseudo-obstruction.
      CONCLUSIONS: It is confirmed that EM, given at subtherapeutic doses, is a
      powerful prokinetic agent that can have clinical applications in patients with
      gastrointestinal dysmotility; however, the effect of the drug seems to be
      influenced by the nature of the underlying disorder.

PMID- 9144125
TI  - Importance of milk and diet on the ontogeny and adaptation of the intestine.

PMID- 9144126
TI  - Clostridium difficile-related necrotizing pseudomembranous enteritis in
      association with Henoch-Schonlein purpura.

PMID- 9144127
TI  - Intrahepatic cholestasis related to vanishing bile duct syndrome in Hodgkin's
      disease.

PMID- 9144128
TI  - Nonspecific duodenitis: an unusual presentation.

PMID- 9144129
TI  - Intrasphincteric injection of Botulinum toxin for treating achalasia in children.

PMID- 9144130
TI  - Use of infant formulas in preventing or postponing atopic manifestations.

PMID- 9144132
TI  - Technique of small-bowel biopsy.

PMID- 9144131
TI  - Botulinum toxin for achalasia: are we witnessing the birth of a new era?

PMID- 9144133
TI  - H2-breath tests--importance of adequate storage of breath samples.

PMID- 9144134
TI  - Free split iliac-bone flap transfer based on the superior gluteal vessels:
      anatomy and case reports.
AB  - Large bone flaps for free transfer can be successfully and safely harvested based
      on the deep branch of the superior gluteal artery. The anatomy is consistent, the
      vessels are large, and the complications of this technique are minimal.

PMID- 9144135
TI  - Neurologic deficit and recovery in the donor limb following cross-C7 transfer in
      brachial-plexus injury.
AB  - Two adult patients with post-traumatic complete brachial plexus injury were
      treated with cross-C7 nerve-root transfer from the contralateral side. A detailed
      documentation of the motor and sensory functional status of the donor upper limb
      was carried out before and after division of the C7 nerve root. Gross motor
      deficits were observed immediately after surgery in shoulder extension and
      adduction, elbow extension, forearm pronation, wrist flexion, and hand movement.
      Sensory deficit involving the hand was maximal immediately after division of the
      C7 root. Functional recovery was rapid starting within 10 days following the root
      division. In both patients, the motor and sensory deficits were temporary. Full
      functional recovery was documented at 6 months. However, objective qualitative
      and quantitative differences in the motor and sensory deficits in the donor limbs
      were still present by 1.5 to 2 years, although these did not affect the
      functional status of the donor limbs. The presence of multiple segmental root
      innervation of the muscles and skin, other than the C7 root in the upper limb,
      provides for a compensatory mechanism that allows for this rapid and full
      functional recovery following the single nerve-root loss. The absence of any long
      term functional deficit makes cross C7 transfer a viable option in the surgical
      management of complete unilateral brachial-plexus injury.

PMID- 9144136
TI  - Vascular cryopreservation in microsurgery.
AB  - Cyropreservation of blood vessels has been carried out for some decades with
      variable results. A rabbit model was used to compare cryopreserved femoral artery
      allografts (n = 12 arteries), fresh autografts (n = 15 arteries), and fresh
      allografts (n = 16 arteries) at 1 and 3 months postoperatively. Patency rates
      were highest in the fresh autografts (86.7 percent), followed by the
      cryopreserved allografts (66.7 percent at 1 month and 83.3 percent at 3 months)
      and fresh allografts (62.5 percent at 1 month and 75 percent at 3 months). The
      fresh allografts showed the greatest alterations in endothelial cells and intima
      and muscle layer, followed by cryopreserved allografts, and then fresh
      autografts. Changes observed included pseudoendothelium formation, thickened
      intima, and thinner muscle layer. Cellular infiltrate appeared on the vessel
      walls only in the cryopreserved allografts (25 percent), but this did not have an
      effect on vascular patency. Fresh autografts remain the graft of choice for
      vascular defects, but cryopreserved allografts serve as the most appropriate
      option when the former are unavailable.

PMID- 9144137
TI  - A new experimental model of a true myocutaneous flap in the rat: the gluteus
      maximus myocutaneous flap.
AB  - Rat myocutaneous flap models are relatively rare. The authors describe the
      development of a new myocutaneous flap model using the gluteus muscle in rats. A
      description of the anatomy of the gluteus maximus is included, along with a
      method of producing skin-island gluteus maximus myocutaneous flaps that can be
      pedicled or free. This flap model may serve as a useful tool in laboratory
      studies of the physiologic or pathologic changes in myocutaneous flaps, and may
      help to narrow the gap between experimental and clinical applications.

PMID- 9144138
TI  - Venous microanastomosis with the Unilink system, sleeve, and suture techniques: a
      comparative study in the rat.
AB  - Multiple microvascular anastomotic techniques have been described with varying
      rates of success. This experimental study presents the results of a comparison of
      three types of venous microanastomotic techniques: the Unilink system, the sleeve
      technique, and the suture technique. Twenty male Sprague-Dawley rats, 40 femoral
      veins, were used for this study. In vivo observation and microvasculography
      demonstrated that patency rates between the Unilink system and suture techniques
      were comparable (p > 0.05) and were significantly superior to the sleeve
      anastomosis (p < 0.05). The anastomotic time for the sleeve technique was
      significantly shorter than for the suture technique (p < 0.001). Compared with
      suture and sleeve anastomoses, the anastomotic time employing the Unilink system
      was significantly the shortest (p < 0.001). The Unilink system proved to be the
      fastest method with the highest patency rate. These results suggest that the use
      of the Unilink system is superior with regard to anastomotic time and patency
      rate, when compared to suture and sleeve techniques for venous microanastomosis.

PMID- 9144139
TI  - Upper-limb-to-lower-limb nerve transfer.

PMID- 9144140
TI  - The arterialized antebrachial skin flap for hand reconstruction.
AB  - The authors present 20 microvascular flaps based on arteriovenous perfusion,
      harvested from the distal anterior forearm, and configured in three different
      designs. Indications were small palmar, dorsal, and commissural defects, when
      other conventional procedures were not available; problematic cases of open
      reduction internal fixation with skin defect; and when aggressive rehabilitation
      was needed. The follow-up varied between 6 and 28 months. Some degree of vascular
      congestion was observed in 100 percent of the flaps, and those changes were
      classified in a progressive form. Coverage was judged as stable, thin, and
      pliable in 75 percent of the cases in the series; aggressive rehabilitation was
      started promptly in all cases where this was possible. On average, an additional
      2.4 hr were required for the original procedure. This flap demands little
      technical expertise for any microsurgical surgeon, and does not sacrifice any
      important donor vessel. The flap should not be followed-up by conventional
      monitoring methods instead, simple palpation of the pulse, Doppler auscultation,
      or PPG are required.

PMID- 9144141
TI  - Coverage of knee-tumor-resection prostheses with free flaps.
AB  - Free latissimus dorsi free flaps were used for the treatment of three patients
      with malignant tumors localized at the distal end of the femur. In all cases, a
      knee prosthesis was used after tumor resection. In two patients, the prosthesis
      was covered with a free latissimus dorsi flap immediately after insertion. In one
      patient, the exposed prosthesis that was inserted 9 months previously was also
      covered with a free latissimus dorsi flap. Histopathologic diagnosis of the
      tumors was osteosarcoma in two cases and fusiform cell sarcoma in one case. Free
      tissue transfers were successful in spite of preoperative chemotherapy and/or
      radiotherapy. Chemotherapy was started 3 weeks postoperatively in all cases.
      Patients ambulated 6 weeks after surgery and knee functions were satisfactory
      during a 1 year follow-up.

PMID- 9144142
TI  - Surgical salvage of failed esophageal reconstruction attempted with gastric
      pedicle.
AB  - Use of the gastric pedicle is an established method for esophageal
      reconstruction. However, fistula or necrosis of the pedicle occasionally occur
      due to vascular insufficiency or the severity of the surgery. During the past 4
      years, the authors encountered six patients with necrosis of the gastric pedicle,
      who required reconstruction of circumferential defects of the cervical and
      thoracic esophagus. In such secondary reconstructive cases, primary closure of
      the wound is very difficult because the surrounding soft tissue becomes fibrous
      from infectious and fistulous complications of the first operation. Free jejunal
      transfers were utilized for restoring continuity of the alimentary tract, a
      platysma myocutaneous and pectoral fasciocutaneous flap for covering the
      intestinal anastomoses, and a mesenteric flap connected with the jejunal graft
      for covering the remaining skin defects in these cases. In follow-up periods from
      3 to 21 months, satisfactory results were obtained in all but one patient. Five
      patients could eat a normal diet without difficulty. This reconstructive method
      is advocated as safe and well-tolerated physiologically in the salvage of
      necrosis of the gastric pedicle.

PMID- 9144143
TI  - Salvage of an avascular thumb by arteriovenous flow reversal and a microvascular
      "kite" flap: case report.
AB  - This case report describes the salvage of an avascular thumb by retrograde venous
      arterialization. The thumb survived with a 30 percent tissue loss at the radial
      aspect. Soft-tissue reconstruction and contour correction were achieved with a
      new microvascular free flap--the free "kite" flap--from the contralateral index
      finger. Aesthetic and functional results were excellent, and the patient returned
      to his original occupation. It can be concluded that retrograde arterialization
      can provide successful salvage in replantation and revascularization under
      favorable circumstances.

PMID- 9144144
TI  - Quantitative morphology of Auerbach's plexus in rat intestinal wall undergoing
      ischemia.
AB  - To clarify the causes of abnormal peristalsis after free jejunum transplantation,
      the authors focused on Auerbach's plexus inducing peristalsis, and conducted an
      experimental study to investigate the relationship between the morphologic
      changes and intestinal ischemic time. Results showed that the sectional area per
      one ganglion cell was reduced statistically significantly at 2 and 4 hr of
      ischemic time, and subsequently remained almost constant. Therefore, it was
      assumed that atrophy of the ganglion cells might occur and might effect abnormal
      peristalsis.

PMID- 9144145
TI  - Iloprost in alginate decreases the thrombogenicity of expanded
      polytetrafluoroethylene.
AB  - Vascular prostheses of small diameter perform poorly in vivo, in part because of
      the high thrombogenicity of available biomaterials. This study examined the
      thrombogenicity of expanded polytetrafluoroethylene (ePTFE) vascular graft
      segments (10 mm long x 4 mm i.d.) in vitro before and after impregnation with
      saline, alginate, or alginate containing the stable prostacyclin analog,
      iloprost. Each segment was immersed in activated whole blood and the weight of
      the adherent thrombus was measured at specified intervals. At 6 and 7 min the
      saline-denucleated group accumulated significantly less thrombus than control (p
      < .05). Alginate alone was not significantly different from controls. The graft
      segments treated with alginate + iloprost accumulated significantly less thrombus
      (p < .05) than all other groups after 6 min. These data demonstrate that
      denucleation of ePTFE with iloprost in alginate dramatically decreases its in
      vitro thrombogenicity.

PMID- 9144146
TI  - Rappaport rules: cleavage furrow induction in animal cells.

PMID- 9144147
TI  - Eubacterial signal transduction by ligands of the mammalian peripheral
      benzodiazepine receptor complex.

PMID- 9144148
TI  - Serotonin, sex, and psychiatric illness.

PMID- 9144149
TI  - A massage for the journey: keeping leukocytes soft and silent.

PMID- 9144155
TI  - Ribozyme-mediated high resistance against potato spindle tuber viroid in
      transgenic potatoes.
AB  - A hammerhead ribozyme [R(-)] targeting the minus strand RNA of potato spindle
      tuber viroid (PSTVd) and a mutated nonfunctional ribozyme [mR(-)] were designed,
      cloned, and transcribed. As predicted, both monomer and dimer transcripts of the
      active R(-) ribozyme gene could cleave the PSTVd minus strand dimer RNA into
      three fragments of 77, 338, and 359 bases in vitro at 25 and 50 degrees C. The
      tandem dimer genes of R(-) and mR(-) were subcloned separately into the plant
      expression vector pROK2. Transgenic potato plants (cultivar Desiree) were
      generated by Agrobacterium tumefaciens-mediated transformation. Twenty-three of
      34 independent transgenic plant lines expressing the active ribozyme R(-)
      resulted in having high levels of resistance to PSTVd, being free of PSTVd
      accumulation after challenge inoculation with PSTVd, but the remaining lines
      showed weaker levels of resistance to PSTVd with low levels of PSTVd
      accumulation. In contrast, 59 of 60 independent transgenic lines expressing the
      mutated ribozyme mR(-) were susceptible to PSTVd inoculation and had levels of
      PSTVd accumulation similar to that of the control plants transformed with the
      empty vector. The resistance against PSTVd replication was stably inherited to
      the vegetative progenies.

PMID- 9144154
TI  - Optical trapping and manipulation of neutral particles using lasers.
AB  - The techniques of optical trapping and manipulation of neutral particles by
      lasers provide unique means to control the dynamics of small particles. These new
      experimental methods have played a revolutionary role in areas of the physical
      and biological sciences. This paper reviews the early developments in the field
      leading to the demonstration of cooling and trapping of neutral atoms in atomic
      physics and to the first use of optical tweezers traps in biology. Some further
      major achievements of these rapidly developing methods also are considered.

PMID- 9144156
TI  - Crystal structure of glutamate-1-semialdehyde aminomutase: an alpha2-dimeric
      vitamin B6-dependent enzyme with asymmetry in structure and active site
      reactivity.
AB  - The three-dimensional structure of glutamate-1-semialdehyde aminomutase (EC
      5.4.3.8), an alpha2-dimeric enzyme from Synechococcus, has been determined by x
      ray crystallography using heavy atom derivative phasing. The structure, refined
      at 2.4-A resolution to an R-factor of 18.7% and good stereochemistry, explains
      many of the enzyme's unusual specificity and functional properties. The overall
      fold is that of aspartate aminotransferase and related B6 enzymes, but it also
      has specific features. The structure of the complex with gabaculine, a substrate
      analogue, shows unexpectedly that the substrate binding site involves residues
      from the N-terminal domain of the molecule, notably Arg-32. Glu-406 is suitably
      positioned to repel alpha-carboxylic acids, thereby suggesting a basis for the
      enzyme's reaction specificity. The subunits show asymmetry in cofactor binding
      and in the mobilities of the residues 153-181. In the unliganded enzyme, one
      subunit has the cofactor bound as an aldimine of pyridoxal phosphate with Lys-273
      and, in this subunit, residues 153-181 are disordered. In the other subunit in
      which the cofactor is not covalently bound, residues 153-181 are well defined.
      Consistent with the crystallographically demonstrated asymmetry, a form of the
      enzyme in which both subunits have pyridoxal phosphate bound to Lys-273 through a
      Schiff base showed biphasic reduction by borohydride in solution. Analysis of
      absorption spectra during reduction provided evidence of communication between
      the subunits. The crystal structure of the reduced form of the enzyme shows that,
      despite identical cofactor binding in each monomer, the structural asymmetry at
      residues 153-181 remains.

PMID- 9144157
TI  - Redesign of soluble fatty acid desaturases from plants for altered substrate
      specificity and double bond position.
AB  - Acyl-acyl carrier protein (ACP) desaturases introduce double bonds at specific
      positions in fatty acids of defined chain lengths and are one of the major
      determinants of the monounsaturated fatty acid composition of vegetable oils.
      Mutagenesis studies were conducted to determine the structural basis for the
      substrate and double bond positional specificities displayed by acyl-ACP
      desaturases. By replacement of specific amino acid residues in a Delta6-palmitoyl
      (16:0)-ACP desaturase with their equivalents from a Delta9-stearoyl (18:0)-ACP
      desaturase, mutant enzymes were identified that have altered fatty acid chain
      length specificities or that can insert double bonds into either the Delta6 or
      Delta9 positions of 16:0- and 18:0-ACP. Most notably, by replacement of five
      amino acids (A181T/A200F/S205N/L206T/G207A), the Delta6-16:0-ACP desaturase was
      converted into an enzyme that functions principally as a Delta9-18:0-ACP
      desaturase. Many of the determinants of fatty acid chain-length specificity in
      these mutants are found in residues that line the substrate binding channel as
      revealed by x-ray crystallography of the Delta9-18:0-ACP desaturase. The
      crystallographic model of the active site is also consistent with the diverged
      activities associated with naturally occurring variant acyl-ACP desaturases. In
      addition, on the basis of the active-site model, a Delta9-18:0-ACP desaturase was
      converted into an enzyme with substrate preference for 16:0-ACP by replacement of
      two residues (L118F/P179I). These results demonstrate the ability to rationally
      modify acyl-ACP desaturase activities through site-directed mutagenesis and
      represent a first step toward the design of acyl-ACP desaturases for the
      production of novel monounsaturated fatty acids in transgenic oilseed crops.

PMID- 9144158
TI  - Investigation of the mechanisms of DNA binding of the human G/T glycosylase using
      designed inhibitors.
AB  - Deamination of 5-methylcytosine residues in DNA gives rise to the G/T mismatched
      base pair. In humans this lesion is repaired by a mismatch-specific thymine DNA
      glycosylase (TDG or G/T glycosylase), which catalyzes specific excision of the
      thymine base through N-glycosidic bond hydrolysis. Unlike other DNA glycosylases,
      TDG recognizes an aberrant pairing of two normal bases rather than a damaged base
      per se. An important structural issue is thus to understand how the enzyme
      specifically targets the T (or U) residue of the mismatched base pair. Our
      approach toward the study of substrate recognition and processing by catalytic
      DNA binding proteins has been to modify the substrate so as to preserve
      recognition of the base but to prevent its excision. Here we report that
      replacement of 2'-hydrogen atoms with fluorine in the substrate 2'-deoxyguridine
      (dU) residue abrogates glycosidic bond cleavage, thereby leading to the formation
      of a tight, specific glycosylase-DNA complex. Biochemical characterization of
      these complexes reveals that the enzyme protects an approximately 20-bp stretch
      of the substrate from DNase I cleavage, and directly contacts a G residue on the
      3' side of the mismatched U derivative. These studies provide a mechanistic
      rationale for the preferential repair of deaminated CpG sites and pave the way
      for future high-resolution studies of TDG bound to DNA.

PMID- 9144160
TI  - Parkinson disease: a new link between monoamine oxidase and mitochondrial
      electron flow.
AB  - Two factors that contribute to the progression of Parkinson disease are a brain
      defect in mitochondrial respiration and the generation of hydrogen peroxide
      (H2O2) by monoamine oxidase (MAO). Here we show that the two are linked.
      Metabolism of the neurotransmitter dopamine, or other monoamines (benzylamine,
      tyramine), by intact rat brain mitochondria suppresses pyruvate- and succinate
      dependent electron transport. MAO inhibitors prevent this action. Mitochondrial
      damage is also reversed during electron flow. A probable explanation is that MAO
      generated H2O2 oxidizes glutathione to glutathione disulfide (GSSG), which
      undergoes thiol-disulfide interchange to form protein mixed disulfides, thereby
      interfering reversibly with thiol-dependent enzymatic function. In agreement with
      this premise, direct addition of GSSG to mitochondria resulted in similar
      reversible inhibition of electron transport. In addition, the monoamines induced
      an elevation in protein mixed disulfides within mitochondria. These observations
      imply that (i) heightened activity and metabolism of neurotransmitter by
      monoamine neurons may affect neuronal function, and (ii) apparent defects in
      mitochondrial respiration associated with Parkinson disease may reflect, in part,
      an established increase in dopamine turnover. The experimental results also
      target mitochondrial repair mechanisms for further investigation and may, in
      time, lead to newer forms of therapy.

PMID- 9144159
TI  - Identification of a new class of protein kinases represented by eukaryotic
      elongation factor-2 kinase.
AB  - The several hundred members of the eukaryotic protein kinase superfamily
      characterized to date share a similar catalytic domain structure, consisting of
      12 conserved subdomains. Here we report the existence and wide occurrence in
      eukaryotes of a protein kinase with a completely different structure. We cloned
      and sequenced the human, mouse, rat, and Caenorhabditis elegans eukaryotic
      elongation factor-2 kinase (eEF-2 kinase) and found that with the exception of
      the ATP-binding site, they do not contain any sequence motifs characteristic of
      the eukaryotic protein kinase superfamily. Comparison of different eEF-2 kinase
      sequences reveals a highly conserved region of approximately 200 amino acids
      which was found to be homologous to the catalytic domain of the recently
      described myosin heavy chain kinase A (MHCK A) from Dictyostelium. This suggests
      that eEF-2 kinase and MHCK A are members of a new class of protein kinases with a
      novel catalytic domain structure.

PMID- 9144162
TI  - Mechanism of protein remodeling by ClpA chaperone.
AB  - ClpA, a newly discovered ATP-dependent molecular chaperone, remodels
      bacteriophage P1 RepA dimers into monomers, thereby activating the latent
      specific DNA binding activity of RepA. We investigated the mechanism of the
      chaperone activity of ClpA by dissociating the reaction into several steps and
      determining the role of nucleotide in each step. In the presence of ATP or a
      nonhydrolyzable ATP analog, the initial step is the self-assembly of ClpA and its
      association with inactive RepA dimers. ClpA-RepA complexes form rapidly and at 0
      degrees C but are relatively unstable. The next step is the conversion of
      unstable ClpA-RepA complexes into stable complexes in a time- and temperature
      dependent reaction. The transition to stable ClpA-RepA complexes requires binding
      of ATP, but not ATP hydrolysis, because nonhydrolyzable ATP analogs satisfy the
      nucleotide requirement. The stable complexes contain approximately 1 mol of RepA
      dimer per mol of ClpA hexamer and are committed to activating RepA. In the last
      step of the reaction, active RepA is released upon exchange of ATP with the
      nonhydrolyzable ATP analog and ATP hydrolysis. Importantly, we discovered that
      one cycle of RepA binding to ClpA followed by ATP-dependent release is sufficient
      to convert inactive RepA to its active form.

PMID- 9144161
TI  - Activation of the orphan nuclear receptor steroidogenic factor 1 by oxysterols.
AB  - Steroidogenic factor 1 (SF-1), an orphan member of the intracellular receptor
      superfamily, plays an essential role in the development and function of multiple
      endocrine organs. It is expressed in all steroidogenic tissues where it regulates
      the P450 steroidogenic genes to generate physiologically active steroids.
      Although many of the functions of SF-1 in vivo have been defined, an unresolved
      question is whether a ligand modulates its transcriptional activity. Here, we
      show that 25-, 26-, or 27-hydroxycholesterol, known suppressors of cholesterol
      biosynthesis, enhance SF-1-dependent transcriptional activity. This activation is
      dependent upon the SF-1 activation function domain, and, is specific for SF-1 as
      several other receptors do not respond to these molecules. The oxysterols
      activate at concentrations comparable to those previously shown to inhibit
      cholesterol biosynthesis, and, can be derived from cholesterol by P450c27, an
      enzyme expressed within steroidogenic tissues. Recent studies have shown that the
      nuclear receptor LXR also is activated by oxysterols. We demonstrate that
      different oxysterols differ in their rank order potency for these two receptors,
      with 25-hydroxycholesterol preferentially activating SF-1 and 22(R)
      hydroxycholesterol preferentially activating LXR. These results suggest that
      specific oxysterols may mediate transcriptional activation via different
      intracellular receptors. Finally, ligand-dependent transactivation of SF-1 by
      oxysterols may play an important role in enhancing steroidogenesis in vivo.

PMID- 9144163
TI  - A sigma32 mutant with a single amino acid change in the highly conserved region
      2.2 exhibits reduced core RNA polymerase affinity.
AB  - sigma32, the product of the rpoH gene in Escherichia coli, provides promoter
      specificity by interacting with core RNAP. Amino acid sequence alignment of
      sigma32 with other sigma factors in the sigma70 family has revealed regions of
      sequence homology. We have investigated the function of the most highly conserved
      region, 2.2, using purified products of various rpoH alleles. Core RNAP binding
      analysis by glycerol gradient sedimentation has revealed reduced core RNAP
      affinity for one of the mutant sigma32 proteins, Q80R. This reduced core
      interaction is exacerbated in the presence of sigma70, which competes with
      sigma32 for binding of core RNAP. When a different but more conserved amino acid
      was introduced at this position by site-directed mutagenesis (Q80N), this mutant
      sigma factor still displayed a significant reduction in its core RNAP affinity.
      Based on these results, we conclude that at least one specific amino acid in
      region 2.2 is involved in core RNAP interaction.

PMID- 9144164
TI  - Structural basis of DNA bending and oriented heterodimer binding by the basic
      leucine zipper domains of Fos and Jun.
AB  - Interactions among transcription factors that bind to separate sequence elements
      require bending of the intervening DNA and juxtaposition of interacting molecular
      surfaces in an appropriate orientation. Here, we examine the effects of single
      amino acid substitutions adjacent to the basic regions of Fos and Jun as well as
      changes in sequences flanking the AP-1 site on DNA bending. Substitution of
      charged amino acid residues at positions adjacent to the basic DNA-binding
      domains of Fos and Jun altered DNA bending. The change in DNA bending was
      directly proportional to the change in net charge for all heterodimeric
      combinations between these proteins. Fos and Jun induced distinct DNA bends at
      different binding sites. Exchange of a single base pair outside of the region
      contacted in the x-ray crystal structure altered DNA bending. Substitution of
      base pairs flanking the AP-1 site had converse effects on the opposite directions
      of DNA bending induced by homodimers and heterodimers. These results suggest that
      Fos and Jun induce DNA bending in part through electrostatic interactions between
      amino acid residues adjacent to the basic region and base pairs flanking the AP-1
      site. DNA bending by Fos and Jun at inverted binding sites indicated that
      heterodimers bind to the AP-1 site in a preferred orientation. Mutation of a
      conserved arginine within the basic regions of Fos and transversion of the
      central C:G base pair in the AP-1 site to G:C had complementary effects on the
      orientation of heterodimer binding and DNA bending. The conformational
      variability of the Fos-Jun-AP-1 complex may contribute to its functional
      versatility at different promoters.

PMID- 9144165
TI  - Dual role of the nuclear factor of activated T cells insert region in DNA
      recognition and cooperative contacts to activator protein 1.
AB  - The transcription factors nuclear factor of activated T cells (NFAT) and
      activator protein 1 (AP-1) coordinately regulate cytokine gene expression in
      activated T-cells by binding to closely juxtaposed sites in cytokine promoters.
      The structural basis for cooperative binding of NFAT and AP-1 to these sites, and
      indeed for the cooperative binding of transcription factors to composite
      regulatory elements in general, is not well understood. Mutagenesis studies have
      identified a segment of AP-1, which lies at the junction of its DNA-binding and
      dimerization domains (basic region and leucine zipper, respectively), as being
      essential for protein-protein interactions with NFAT in the ternary NFAT/AP-1/DNA
      complex. In a model of the ternary complex, the segment of NFAT nearest AP-1 is
      the Rel insert region (RIR), a feature that is notable for its hypervariability
      in size and in sequence amongst members of the Rel transcription factor family.
      Here we have used mutational analysis to study the role of the NFAT RIR in
      binding to DNA and AP-1. Parallel yeast one-hybrid screening assays in
      combination with alanine-scanning mutagenesis led to the identification of four
      amino acid residues in the RIR of NFAT2 (also known as NFATC1 or NFATc) that are
      essential for cooperativity with AP-1 (Ile-544, Glu-545, Thr-551, and Ile-553),
      and three residues that are involved in interactions with DNA (Lys-538, Arg-540,
      and Asn-541). These results were confirmed and extended through in vitro binding
      assays. We thus conclude that the NFAT RIR plays an essential dual role in DNA
      recognition and cooperative binding to AP-1 family transcription factors.

PMID- 9144166
TI  - Cyp7b, a novel brain cytochrome P450, catalyzes the synthesis of neurosteroids
      7alpha-hydroxy dehydroepiandrosterone and 7alpha-hydroxy pregnenolone.
AB  - Steroids produced locally in brain (neurosteroids), including
      dehydroepiandrosterone (DHEA), influence cognition and behavior. We previously
      described a novel cytochrome P450, Cyp7b, strongly expressed in rat and mouse
      brain, particularly in hippocampus. Cyp7b is most similar to steroidogenic P450s
      and potentially could play a role in neurosteroid metabolism. To examine the
      catalytic activity of the enzyme mouse Cyp7b cDNA was introduced into a vaccinia
      virus vector. Extracts from cells infected with the recombinant showed NADPH
      dependent conversion of DHEA (Km, 13.6 microM) and pregnenolone (Km, 4.0 microM)
      to slower migrating forms on thin layer chromatography. The expressed enzyme was
      less active against 25-hydroxycholesterol, 17beta-estradiol and 5alpha-androstane
      3beta,17beta-diol, with low to undetectable activity against progesterone,
      corticosterone, and testosterone. On gas chromatography and mass spectrometry of
      the Cyp7b metabolite of DHEA the retention time and fragmentation patterns were
      identical to those obtained with authentic 7alpha-hydroxy DHEA. The reaction
      product also comigrated on thin layer chromatography with 7alpha-hydroxy DHEA but
      not with 7beta-hydroxy DHEA; when [7alpha-3H]pregnenolone was incubated with
      Cyp7b extracts the extent of release of radioactivity into the medium suggested
      that hydroxylation was preferentially at the 7alpha position. Brain extracts also
      efficiently liberated tritium from [7alpha-3H]pregnenolone and converted DHEA to
      a product with a chromatographic mobility indistinguishable from 7alpha-hydroxy
      DHEA. We conclude that Cyp7b is a 7alpha-hydroxylase participating in the
      synthesis, in brain, of neurosteroids 7alpha-hydroxy DHEA, and 7alpha-hydroxy
      pregnenolone.

PMID- 9144167
TI  - Scrapie susceptibility-linked polymorphisms modulate the in vitro conversion of
      sheep prion protein to protease-resistant forms.
AB  - Prion diseases are natural transmissible neurodegenerative disorders in humans
      and animals. They are characterized by the accumulation of a protease-resistant
      scrapie-associated prion protein (PrPSc) of the host-encoded cellular prion
      protein (PrPC) mainly in the central nervous system. Polymorphisms in the PrP
      gene are linked to differences in susceptibility for prion diseases. The
      mechanisms underlying these effects are still unknown. Here we describe studies
      of the influence of sheep PrP polymorphisms on the conversion of PrPC into
      protease-resistant forms. In a cell-free system, sheep PrPSc induced the
      conversion of sheep PrPC into protease-resistant PrP (PrP-res) similar or
      identical to PrPSc. Polymorphisms present in either PrPC or PrPSc had dramatic
      effects on the cell-free conversion efficiencies. The PrP variant associated with
      a high susceptibility to scrapie and short survival times of scrapie-affected
      sheep was efficiently converted into PrP-res. The wild-type PrP variant
      associated with a neutral effect on susceptibility and intermediate survival
      times was converted with intermediate efficiency. The PrP variant associated with
      scrapie resistance and long survival times was poorly converted. Thus the in
      vitro conversion characteristics of the sheep PrP variants reflect their linkage
      with scrapie susceptibility and survival times of scrapie-affected sheep. The
      modulating effect of the polymorphisms in PrPC and PrPSc on the cell-free
      conversion characteristics suggests that, besides the species barrier,
      polymorphism barriers play a significant role in the transmissibility of prion
      diseases.

PMID- 9144168
TI  - In vitro selection and evolution of functional proteins by using ribosome
      display.
AB  - We report here a system with which a correctly folded complete protein and its
      encoding mRNA both remain attached to the ribosome and can be enriched for the
      ligand-binding properties of the native protein. We have selected a single-chain
      fragment (scFv) of an antibody 10(8)-fold by five cycles of transcription,
      translation, antigen-affinity selection, and PCR. The selected scFv fragments all
      mutated in vitro by acquiring up to four unrelated amino acid exchanges over the
      five generations, but they remained fully compatible with antigen binding.
      Libraries of native folded proteins can now be screened and made to evolve in a
      cell-free system without any transformation or constraints imposed by the host
      cell.

PMID- 9144169
TI  - Characterization and tissue-specific expression of the rat basic fibroblast
      growth factor antisense mRNA and protein.
AB  - An RNA transcribed from the antisense strand of the FGF-2 gene has been
      implicated in the regulation of FGF-2 mRNA stability in amphibian oocytes. We
      have now cloned and characterized a novel 1. 1-kb mRNA (fgf-as) from neonatal rat
      liver. In non-central nervous system (CNS) tissues the fgf-as RNA is abundantly
      expressed in a developmentally regulated manner. The FGF-AS cDNA contains a
      consensus polyadenylylation signal and a long open reading frame (ORF) whose
      deduced amino acid sequence predicts a 35-kDa protein with homology to the MutT
      family of nucleotide hydrolases. Western blot analysis with antibodies against
      the deduced peptide sequence demonstrates that the FGF-AS protein is expressed in
      a broad range of non-CNS tissue in the postnatal period. In the developing brain,
      the abundance of sense and antisense transcripts are inversely related,
      suggesting a role for the antisense RNA in posttranscriptional regulation of FGF
      2 expression in this tissue. The FGF-AS is complementary to two widely separated
      regions in the long 3' untranslated region of the FGF-2 mRNA, in the vicinity of
      the proximal and distal polyadenylylation sites. These findings demonstrate that
      the FGF-2 and fgf-as RNAs are coordinately transcribed on a tissue-specific and
      developmentally regulated basis and suggest that interaction of the sense and
      antisense RNAs may result in posttranscriptional regulation of FGF-2 in some
      tissues.

PMID- 9144170
TI  - E2F4-RB and E2F4-p107 complexes suppress gene expression by transforming growth
      factor beta through E2F binding sites.
AB  - Transforming growth factor beta (TGF-beta) causes growth arrest in most cell
      types. TGF-beta induces hypophosphorylation of retinoblastoma susceptibility gene
      1 product (RB), which sequesters E2F factors needed for progression into S phase
      of the cell cycle, thereby leading to cell cycle arrest at G1. It is possible,
      however, that the E2F-RB complex induced by TGF-beta may bind to E2F sites and
      suppress expression of specific genes whose promoters contain E2F binding sites.
      We show here that TGF-beta treatment of HaCaT cells induced the formation of E2F4
      RB and E2F4-p107 complexes, which are capable of binding to E2F sites. Disruption
      of their binding to DNA with mutation in the E2F sites did not change the
      expression from promoters of E2F1, B-myb, or HsORC1 genes in cycling HaCaT cells.
      However, the same mutation stimulated 5- to 6-fold higher expression from all
      three promoters in cells treated with TGF-beta. These results suggest that E2F
      binding sites play an essential role in the transcription repression of these
      genes under TGF-beta treatment. Consistent with their repression of TGF-beta
      induced gene expression, introduction of E2F sites into the promoter of cyclin
      dependent kinase inhibitor p15(INK4B) gene effectively inhibited its induction by
      TGF-beta. Experiments utilizing Gal4-RB and Gal4-p107 chimeric constructs
      demonstrated that either RB or p107 could directly repress TGF-beta induction of
      p15(INK4B) gene when tethered to p15(INK4B) promoter through Gal4 DNA binding
      sites. Therefore, E2F functions to bring RB and p107 to E2F sites and represses
      gene expression by TGF-beta. These results define a specific function for E2F4-RB
      and E2F4-p107 complexes in gene repression under TGF-beta treatment, which may
      constitute an integral part of the TGF-beta-induced growth arrest program.

PMID- 9144171
TI  - Protein binding and signaling properties of RIN1 suggest a unique effector
      function.
AB  - Human RIN1 was first characterized as a RAS binding protein based on the
      properties of its carboxyl-terminal domain. We now show that full-length RIN1
      interacts with activated RAS in mammalian cells and defines a minimum region of
      434 aa required for efficient RAS binding. RIN1 interacts with the "effector
      domain" of RAS and employs some RAS determinants that are common to, and others
      that are distinct from, those required for the binding of RAF1, a known RAS
      effector. The same domain of RIN1 that binds RAS also interacts with 14-3-3
      proteins, extending the similarity between RIN1 and other RAS effectors. When
      expressed in mammalian cells, the RAS binding domain of RIN1 can act as a
      dominant negative signal transduction blocker. The amino-terminal domain of RIN1
      contains a proline-rich sequence similar to consensus Src homology 3 (SH3)
      binding regions. This RIN1 sequence shows preferential binding to the ABL-SH3
      domain in vitro. Moreover, the amino-terminal domain of RIN1 directly associates
      with, and is tyrosine phosphorylated by, c-ABL. In addition, RIN1 encodes a
      functional SH2 domain that has the potential to activate downstream signals.
      These data suggest that RIN1 is able to mediate multiple signals. A differential
      pattern of expression and alternate splicing indicate several levels of RIN1
      regulation.

PMID- 9144172
TI  - Constitutive signaling by the phototaxis receptor sensory rhodopsin II from
      disruption of its protonated Schiff base-Asp-73 interhelical salt bridge.
AB  - Sensory rhodopsin II (SRII) is a repellent phototaxis receptor in the archaeon
      Halobacterium salinarum, similar to visual pigments in its seven-helix structure
      and linkage of retinal to the protein by a protonated Schiff base in helix G. Asp
      73 in helix C is shown by spectroscopic analysis to be a counterion to the
      protonated Schiff base in the unphotolyzed SRII and to be the proton acceptor
      from the Schiff base during photoconversion to the receptor signaling state.
      Coexpression of the genes encoding mutated SRII with Asn substituted for Asp-73
      (D73N) and the SRII transducer HtrII in H. salinarum cells results in a 3-fold
      higher swimming reversal frequency accompanied by demethylation of HtrII in the
      dark, showing that D73N SRII produces repellent signals in its unphotostimulated
      state. Analogous constitutive signaling has been shown to be produced by the
      similar neutral residue substitution of the Schiff base counterion and proton
      acceptor Glu-113 in human rod rhodopsin. The interpretation for both seven-helix
      receptors is that light activation of the wild-type protein is caused primarily
      by photoisomerization-induced transfer of the Schiff base proton on helix G to
      its primary carboxylate counterion on helix C. Therefore receptor activation by
      helix C-G salt-bridge disruption in the photoactive site is a general mechanism
      in retinylidene proteins spanning the vast evolutionary distance between archaea
      and humans.

PMID- 9144174
TI  - Three small nucleolar RNAs that are involved in ribosomal RNA precursor
      processing.
AB  - Three small nucleolar RNAs (snoRNAs), E1, E2 and E3, have been described that
      have unique sequences and interact directly with unique segments of pre-rRNA in
      vivo. In this report, injection of antisense oligodeoxynucleotides into Xenopus
      laevis oocytes was used to target the specific degradation of these snoRNAs.
      Specific disruptions of pre-rRNA processing were then observed, which were
      reversed by injection of the corresponding in vitro-synthesized snoRNA.
      Degradation of each of these three snoRNAs produced a unique rRNA maturation
      phenotype. E1 RNA depletion shut down 18 rRNA formation, without overaccumulation
      of 20S pre-rRNA. After E2 RNA degradation, production of 18S rRNA and 36S pre
      rRNA stopped, and 38S pre-rRNA accumulated, without overaccumulation of 20S pre
      rRNA. E3 RNA depletion induced the accumulation of 36S pre-rRNA. This suggests
      that each of these snoRNAs plays a different role in pre-rRNA processing and
      indicates that E1 and E2 RNAs are essential for 18S rRNA formation. The available
      data support the proposal that these snoRNAs are at least involved in pre-rRNA
      processing at the following pre-rRNA cleavage sites: E1 at the 5' end and E2 at
      the 3' end of 18S rRNA, and E3 at or near the 5' end of 5.8S rRNA.

PMID- 9144175
TI  - Trigger factor is induced upon cold shock and enhances viability of Escherichia
      coli at low temperatures.
AB  - Trigger factor (TF) in Escherichia coli is a molecular chaperone with remarkable
      properties: it has prolyl-isomerase activity, associates with nascent
      polypeptides on ribosomes, binds to GroEL, enhances GroEL's affinity for unfolded
      proteins, and promotes degradation of certain polypeptides. Because the latter
      effects appeared larger at 20 degrees C, we studied the influence of temperature
      on TF expression. Unlike most chaperones (e.g., GroEL), which are heat-shock
      proteins (hsps), TF levels increased progressively as growth temperature
      decreased from 42 degrees C to 16 degrees C and even rose in cells stored at 4
      degrees C. Upon temperature downshift from 37 degrees C to 10 degrees C or
      exposure to chloramphenicol, TF synthesis was induced, like that of many cold
      shock proteins. We therefore tested if TF expression might be important for
      viability at low temperatures. When stored at 4 degrees C, E. coli lose viability
      at exponential rates. Cells with reduced TF content die faster, while cells
      overexpressing TF showed greater viability. Although TF overproduction protected
      against cold, it reduced viability at 50 degrees C, while TF deficiency enhanced
      viability at this temperature. By contrast, overproduction of GroEL/ES, or hsps
      generally, while protective against high temperatures, reduced viability at 4
      degrees C, which may explain why expression of hsps is suppressed in the cold.
      Thus, TF represents an example of an E. coli protein which protects cells against
      low temperatures. Moreover, the differential induction of TF at low temperatures
      and hsps at high temperatures appears to provide selective protection against
      these opposite thermal extremes.

PMID- 9144173
TI  - Expression, stability, and membrane integration of truncation mutants of bovine
      rhodopsin.
AB  - Premature termination of protein synthesis by nonsense mutations is at the
      molecular origin of a number of inherited disorders in the family of G protein
      coupled seven-helix receptor proteins. To understand how such truncated
      polypeptides are processed by the cell, we have carried out COS-1 cell expression
      studies of mutants of bovine rhodopsin truncated at the first 1, 1.5, 2, 3, or 5
      transmembrane segments (TMS) of the seven present in wild-type opsin. Our
      experiments show that successful completion of different stages in the cellular
      processing of the protein [membrane insertion, N-linked glycosylation, stability
      to proteolytic degradation, and transport from the endoplasmic reticulum (ER)
      membrane] requires progressively longer lengths of the polypeptide chain. Thus,
      none of the truncations affected the ability of the polypeptides to be integral
      membrane proteins. C-terminal truncations that generated polypeptides with fewer
      than two TMS resulted in misorientation and prevented glycosylation at the N
      terminus, whereas truncations that generated polypeptides with fewer than five
      TMS greatly destabilized the protein. However, all of the truncations prevented
      exit of the polypeptide from the ER. We conclude that during the biogenesis of
      rhodopsin, proper integration into the ER membrane occurs only after the
      synthesis of at least two TMS is completed. Synthesis of the next three TMS
      confers a gradual increase in stability, whereas the presence of more than five
      TMS is necessary for exit from the ER.

PMID- 9144176
TI  - RNA polymerase sigma factor determines start-site selection but is not required
      for upstream promoter element activation on heteroduplex (bubble) templates.
AB  - Sequence-selective transcription by bacterial RNA polymerase (RNAP) requires
      sigma factor that participates in both promoter recognition and DNA melting. RNAP
      lacking sigma (core enzyme) will initiate RNA synthesis from duplex ends, nicks,
      gaps, and single-stranded regions. We have used DNA templates containing short
      regions of heteroduplex (bubbles) to compare initiation in the presence and
      absence of various sigma factors. Using bubble templates containing the sigmaD
      dependent flagellin promoter, with or without its associated upstream promoter
      (UP) element, we demonstrate that UP element stimulation occurs efficiently even
      in the absence of sigma. This supports a model in which the UP element acts
      primarily through the alpha subunit of core enzyme to increase the initial
      association of RNAP with the promoter. Core and holoenzyme do differ
      substantially in the template positions chosen for initiation: sigmaD restricts
      initiation to sites 8-9 nucleotides downstream of the conserved -10 element.
      Remarkably, sigmaA also has a dramatic effect on start-site selection even though
      the sigmaA holoenzyme is inactive on the corresponding homoduplexes. The start
      sites chosen by the sigmaA holoenzyme are located 8 nucleotides downstream of
      sequences on the nontemplate strand that resemble the conserved -10 hexamer
      recognized by sigmaA. Thus, sigmaA appears to recognize the -10 region even in a
      single-stranded state. We propose that in addition to its described roles in
      promoter recognition and start-site melting, sigma also localizes the
      transcription start site.

PMID- 9144178
TI  - DAD1, the defender against apoptotic cell death, is a subunit of the mammalian
      oligosaccharyltransferase.
AB  - DAD1, the defender against apoptotic cell death, was initially identified as a
      negative regulator of programmed cell death in the BHK21-derived tsBN7 cell line.
      Of interest, the 12.5-kDa DAD1 protein is 40% identical in sequence to Ost2p, the
      16-kDa subunit of the yeast oligosaccharyltransferase (OST). Although the latter
      observation suggests that DAD1 may be a mammalian OST subunit, biochemical
      evidence to support this hypothesis has not been reported. Previously, we showed
      that canine OST activity is associated with an oligomeric complex of ribophorin
      I, ribophorin II, and OST48. Here, we demonstrate that DAD1 is a tightly
      associated subunit of the OST both in the intact membrane and in the purified
      enzyme. Sedimentation velocity analyses of detergent-solubilized WI38 cells and
      canine rough microsomes show that DAD1 cosediments precisely with OST activity
      and with the ribophorins and OST48. Radioiodination of the purified OST reveals
      that DAD1 is present in roughly equimolar amounts relative to the other subunits.
      DAD1 can be crosslinked to OST48 in intact microsomes with
      dithiobis(succinimidylpropionate). Crosslinked ribophorin II-OST48 heterodimers,
      DAD1-ribophorin II-OST48 heterotrimers and DAD1-ribophorin I-ribophorin II-OST48
      heterotetramers also were detected. The demonstration that DAD1 is a subunit of
      the OST suggests that induction of a cell death pathway upon loss of DAD1 in the
      tsBN7 cell line reflects the essential nature of N-linked glycosylation in
      eukaryotes.

PMID- 9144177
TI  - Cloning and characterization of TDD5, an androgen target gene that is
      differentially repressed by testosterone and dihydrotestosterone.
AB  - By using mRNA polymerase chain reaction differential display technique (DDPCR),
      we have identified one early responsive cDNA fragment, TDD5, from a 5alpha
      reductase-deficient T cell hybridoma. The DDPCR profiles of TDD5 suggest that its
      expression can be repressed by testosterone (T) within 2 hr. More importantly,
      both DDPCR and Northern blot analysis further demonstrated that the expression of
      TDD5 was differentially repressed by T and dihydrotestosterone (DHT) at the mRNA
      level. To our knowledge, this is the first androgen target gene to show a
      preference in response to T over DHT in cell culture. TDD5 is expressed in
      several tissues with particular abundance in kidney. Full-length TDD5 cDNA (2,916
      bp) encodes a protein with a calculated molecular weight of 42,000. Finally, our
      animal studies further confirm that TDD5 mRNA levels can be repressed to the
      basal level 8 hr after DHT administration. The isolation and characterization of
      the early-responsive androgen target gene TDD5 and the fact that TDD5 mRNA level
      can be differentially regulated by T and DHT may provide a useful tool to study
      the molecular mechanism of androgen preference on target gene regulation.

PMID- 9144179
TI  - The active oligomeric state of the minimalistic influenza virus M2 ion channel is
      a tetramer.
AB  - The influenza A virus M2 integral membrane protein is an ion channel that permits
      protons to enter virus particles during uncoating of virions in endosomes and
      also modulates the pH of the trans-Golgi network in virus-infected cells. The M2
      protein is a homo-oligomer of 97 residues, and analysis by chemical cross-linking
      and SDS/PAGE indicates M2 forms a tetramer. However, a higher order molecular
      form is sometimes observed and, thus, it is necessary to determine the active
      form of the molecule. This was done by studying the currents of oocytes that
      expressed mixtures of the wild-type M2 protein (epitope tagged) and the mutant
      protein M2-V27S, which is resistant to the inhibitor amantadine. The composition
      of mixed oligomers of the two proteins expressed at the plasma membrane of
      individual oocytes was quantified after antibody capture of the cell surface
      expressed molecules and it was found that the subunits mixed freely. When the
      ratio of wild-type to mutant protein subunits was 0. 85:0.15, the amantadine
      sensitivity was reduced to 50% and for a ratio of 0.71:0.29 to 20%. These results
      are consistent with the amantadine-resistant mutant being dominant and the
      oligomeric state being a tetramer.

PMID- 9144180
TI  - Two domains within sigmaN (sigma54) cooperate for DNA binding.
AB  - The sigma-N (sigmaN) subunit of the bacterial RNA polymerase is a sequence
      specific DNA-binding protein. The RNA polymerase holoenzyme formed with sigmaN
      binds to promoters in an inactive form and only initiates transcription when
      activated by enhancer-binding positive control proteins. We now provide evidence
      to show that the DNA-binding activity of sigmaN involves two distinct domains: a
      C-terminal DNA-binding domain that directly contacts DNA and an adjacent domain
      that enhances DNA-binding activity. The sequences required for the enhancement of
      DNA binding can be separated from the sequences required for core RNA polymerase
      binding. These results provide strong evidence for communication between domains
      within a transcription factor, likely to be important for the function of sigmaN
      in enhancer-dependent transcription.

PMID- 9144181
TI  - The dTTPase mechanism of T7 DNA helicase resembles the binding change mechanism
      of the F1-ATPase.
AB  - Bacteriophage T7 DNA helicase is a ring-shaped hexamer that catalyzes duplex DNA
      unwinding using dTTP hydrolysis as an energy source. Of the six potential
      nucleotide binding sites on the hexamer, we have found that three are
      noncatalytic sites and three are catalytic sites. The noncatalytic sites bind
      nucleotides with a high affinity, but dTTPs bound to these sites do not
      dissociate or hydrolyze through many dTTPase turnovers at the catalytic sites.
      The catalytic sites show strong cooperativity which leads to sequential binding
      and hydrolysis of dTTP. The elucidated dTTPase mechanism of the catalytic sites
      of T7 helicase is remarkably similar to the binding change mechanism of the ATP
      synthase. Based on the similarity, a general mechanism for hexameric helicases is
      proposed. In this mechanism, an F1-ATPase-like rotational movement around the
      single-stranded DNA, which is bound through the central hole of the hexamer, is
      proposed to lead to unidirectional translocation along single-stranded DNA and
      duplex DNA unwinding.

PMID- 9144182
TI  - Cross-validated maximum likelihood enhances crystallographic simulated annealing
      refinement.
AB  - Recently, the target function for crystallographic refinement has been improved
      through a maximum likelihood analysis, which makes proper allowance for the
      effects of data quality, model errors, and incompleteness. The maximum likelihood
      target reduces the significance of false local minima during the refinement
      process, but it does not completely eliminate them, necessitating the use of
      stochastic optimization methods such as simulated annealing for poor initial
      models. It is shown that the combination of maximum likelihood with cross
      validation, which reduces overfitting, and simulated annealing by torsion angle
      molecular dynamics, which simplifies the conformational search problem, results
      in a major improvement of the radius of convergence of refinement and the
      accuracy of the refined structure. Torsion angle molecular dynamics and the
      maximum likelihood target function interact synergistically, the combination of
      both methods being significantly more powerful than each method individually.
      This is demonstrated in realistic test cases at two typical minimum Bragg
      spacings (dmin = 2.0 and 2.8 A, respectively), illustrating the broad
      applicability of the combined method. In an application to the refinement of a
      new crystal structure, the combined method automatically corrected a mistraced
      loop in a poor initial model, moving the backbone by 4 A.

PMID- 9144183
TI  - The emergence of form by replication.
AB  - It is shown with a simple mathematical model that if a system exhibits a given
      form (a spatial structure) and is put in contact with another system of the same
      type but in a state of spatial disorder, then under certain conditions their
      mutual interaction as they evolve in time allows replication of form in the
      disordered system with a controllable degree of faithfulness.

PMID- 9144184
TI  - Reducing the flexibility of retinal restores a wild-type-like photocycle in
      bacteriorhodopsin mutants defective in protein-retinal coupling.
AB  - The thermal re-isomerization of retinal from the 13-cis to the all-trans state is
      a key step in the final stages of the photocycle of the light-driven proton pump,
      bacteriorhodopsin. This step is greatly slowed upon replacement of Leu-93, a
      residue in van der Waals contact with retinal. The most likely role of this key
      interaction is that it restricts the flexibility of retinal. To test this
      hypothesis, we have exchanged native retinal in Leu-93 mutants with bridged
      retinal analogs that render retinal less flexible by restricting free rotation
      around either the C10-C11 (9,11-bridged retinal) or C12-C13 (11,13-bridged
      retinal) single bonds. The effect of the analogs on the photocycle was then
      determined spectroscopically by taking advantage of the previous finding that the
      decay of the O intermediate in the Leu-93 mutants provides a convenient marker
      for retinal re-isomerization. Time-resolved spectroscopic studies showed that
      both retinal analogs resulted in a dramatic acceleration of the photocycling time
      by increasing the rate of decay of the O intermediate. In particular, exchange of
      native retinal in the Leu-93 --> Ala mutant with the 9,11-bridged retinal
      resulted in an acceleration of the decay of the O intermediate to a rate similar
      to that seen in wild-type bacteriorhodopsin. We conclude that the protein-induced
      restriction of conformational flexibility in retinal is a key structural
      requirement for efficient protein-retinal coupling in the bacteriorhodopsin
      photocycle.

PMID- 9144185
TI  - Signal changes in the spinal cord of the rat after injection of formalin into the
      hindpaw: characterization using functional magnetic resonance imaging.
AB  - Changes in metabolism and local circulation occur in the spinal cord during
      peripheral noxious stimulation. Evidence is presented that this stimulation also
      causes signal intensity alterations in functional magnetic resonance images of
      the spinal cord during formalin-induced pain. These results indicate the
      potential of functional magnetic resonance imaging in assessing noninvasively the
      extent and intensity of spinal cord excitation in this well characterized pain
      model. Therefore, the aim of this study was to establish functional magnetic
      resonance imaging as a noninvasive method to characterize temporal changes in the
      spinal cord after a single injection of 50 microl of formalin subcutaneously into
      the hindpaw of the anesthetized rat. This challenge produced a biphasic licking
      activity in the freely moving conscious animal. Images of the spinal cord were
      acquired within 2 min, enabling monitoring of the site and the temporal evolution
      of the signal changes during the development of formalin-induced hyperalgesia
      without the need of any surgical procedure. The time course of changes in the
      spinal cord functional image in the isoflurane-anesthetized animal was similar to
      that obtained from behavioral experiments. Also, comparable physiological data,
      control experiments, and the inhibition of a response through application of the
      local anesthetic agent lidocaine indicate that the signal changes observed after
      formalin injection were specifically related to excitability changes in the
      relevant segments of the lumbar spinal cord. This approach could be useful to
      characterize different models of pain and hyperalgesia and, more importantly, to
      evaluate effects of analgesic drugs.

PMID- 9144187
TI  - Cell membrane fluctuations are regulated by medium macroviscosity: evidence for a
      metabolic driving force.
AB  - Extracellular fluid macroviscosity (EFM), modified by macromolecular cosolvents
      as occurs in body fluids, has been shown to affect cell membrane protein
      activities but not isolated proteins. In search for the mechanism of this
      phenomenon, we examined the effect of EFM on mechanical fluctuations of the cell
      membrane of human erythrocytes. The macroviscosity of the external medium was
      varied by adding to it various macromolecules [dextrans (70, 500, and 2,000 kDa),
      polyethylene glycol (20 kDa), and carboxymethyl-cellulose (100 kDa)], which
      differ in size, chemical nature, and in their capacity to increase fluid
      viscosity. The parameters of cell membrane fluctuations (maximal amplitude and
      half-width of amplitude distribution) were diminished with the elevation of
      solvent macroviscosity, regardless of the cosolvent used to increase EFM. Because
      thermally driven membrane fluctuations cannot be damped by elevation of EFM, the
      existence of a metabolic driving force is suggested. This is supported by the
      finding that in ATP-depleted red blood cells elevation of EMF did not affect cell
      membrane fluctuations. This study demonstrates that (i) EFM is a regulator of
      membrane dynamics, providing a possible mechanism by which EFM affects cell
      membrane activities; and (ii) cell membrane fluctuations are driven by a
      metabolic driving force in addition to the thermal one.

PMID- 9144186
TI  - A local electrostatic change is the cause of the large-scale protein conformation
      shift in bacteriorhodopsin.
AB  - During light-driven proton transport bacteriorhodopsin shuttles between two
      protein conformations. A large-scale structural change similar to that in the
      photochemical cycle is produced in the D85N mutant upon raising the pH, even
      without illumination. We report here that (i) the pKa values for the change in
      crystallographic parameters and for deprotonation of the retinal Schiff base are
      the same, (ii) the retinal isomeric configuration is nearly unaffected by the
      protein conformation, and (iii) preventing rotation of the C13-C14 double bond by
      replacing the retinal with an all-trans locked analogue makes little difference
      to the Schiff base pKa. We conclude that the direct cause of the conformational
      shift is destabilization of the structure upon loss of interaction of the
      positively charged Schiff base with anionic residues that form its counter-ion.

PMID- 9144189
TI  - Karyopherin beta2 mediates nuclear import of a mRNA binding protein.
AB  - We have cloned and sequenced cDNA for human karyopherin beta2, also known as
      transportin. In a solution binding assay, recombinant beta2 bound directly to
      recombinant nuclear mRNA-binding protein A1. Binding was inhibited by a peptide
      representing A1's previously characterized M9 nuclear localization sequence
      (NLS), but not by a peptide representing a classical NLS. As previously shown for
      karyopherin beta1, karyopherin beta2 bound to several nucleoporins containing
      characteristic peptide repeat motifs. In a solution binding assay, both beta1 and
      beta2 competed with each other for binding to immobilized repeat nucleoporin
      Nup98. In digitonin-permeabilized cells, beta2 was able to dock A1 at the nuclear
      rim and to import it into the nucleoplasm. At low concentrations of beta2, there
      was no stimulation of import by the exogenous addition of the GTPase Ran.
      However, at higher concentrations of beta2 there was marked stimulation of import
      by Ran. Import was inhibited by the nonhydrolyzable GTP analog guanylyl
      imidodiphosphate by a Ran mutant that is unable to hydrolyze GTP and also by
      wheat germ agglutinin. Consistent with the solution binding results, karyopherin
      beta2 inhibited karyopherin alpha/beta1-mediated import of a classical NLS
      containing substrate and, vice versa, beta1 inhibited beta2-mediated import of A1
      substrate, suggesting that the two import pathways merge at the level of docking
      of beta1 and beta2 to repeat nucleoporins.

PMID- 9144190
TI  - Molecular uncoupling of C-C chemokine receptor 5-induced chemotaxis and signal
      transduction from HIV-1 coreceptor activity.
AB  - The C-C chemokine receptor 5 (CCR5) plays a crucial role in facilitating the
      entry of macrophage-tropic strains of the HIV-1 into cells, but the mechanism of
      this phenomenon is completely unknown. To explore the role of CCR5-derived signal
      transduction in viral entry, we introduced mutations into two cytoplasmic domains
      of CCR5 involved in receptor-mediated function. Truncation of the terminal
      carboxyl-tail to eight amino acids or mutation of the highly conserved aspartate
      arginine-tyrosine, or DRY, sequence in the second cytoplasmic loop of CCR5
      effectively blocked chemokine-dependent activation of classic second messengers,
      intracellular calcium fluxes, and the cellular response of chemotaxis. In
      contrast, none of the mutations altered the ability of CCR5 to act as an HIV-1
      coreceptor. We conclude that the initiation of signal transduction, the
      prototypic function of G protein coupled receptors, is not required for CCR5 to
      act as a coreceptor for HIV-1 entry into cells.

PMID- 9144191
TI  - Regulation of Bcl-xL expression in human keratinocytes by cell-substratum
      adhesion and the epidermal growth factor receptor.
AB  - Cell-substratum adhesion is an essential requirement for survival of human
      neonatal keratinocytes in vitro. Similarly, activation of the epidermal growth
      factor receptor (EGF-R) has recently been implicated not only in cell cycle
      progression but also in survival of normal keratinocytes. The mechanisms by which
      either cell-substratum adhesion or EGF-R activation protect keratinocytes from
      programmed cell death are poorly understood. Here we describe that blockade of
      the EGF-R and inhibition of substratum adhesion share a common downstream event,
      the down-regulation of the cell death protector Bcl-xL. Expression of Bcl-xL
      protein was down-regulated during forced suspension culture of keratinocytes,
      concurrent with large-scale apoptosis. Similarly, EGF-R blockade was accompanied
      by down-regulation of Bcl-xL steady-state mRNA and protein levels to an extent
      comparable to that observed in forced suspension culture. However, down
      regulation of Bcl-xL expression by EGF-R blockade was not accompanied by
      apoptosis; in this case, a second signal, generated by passaging, was required to
      induce rapid and large-scale apoptosis. These findings are consistent with the
      conclusions that (i) Bcl-xL represents a shared molecular target for signaling
      through cell-substrate adhesion receptors and the EGF-R, and (ii) reduced levels
      of Bcl-xL expression through EGF-R blockade lower the tolerance of keratinocytes
      for cell death signals generated by cellular stress.

PMID- 9144193
TI  - Microtubule release from the centrosome.
AB  - Although microtubules (MTs) are generally thought to originate at the centrosome,
      a number of cell types have significant populations of MTs with no apparent
      centrosomal connection. The origin of these noncentrosomal MTs has been unclear.
      We applied kinetic analysis of MT formation in vivo to establish their mode of
      origin. Time-lapse fluorescence microscopy demonstrated that noncentrosomal MTs
      in cultured epithelial cells arise primarily by constitutive nucleation at, and
      release from, the centrosome. After release, MTs moved away from the centrosome
      and tended to depolymerize. Laser-marking experiments demonstrated that released
      MTs moved individually with their plus ends leading, suggesting that they were
      transported by minus end-directed motors. Released MTs were dynamic. The laser
      marking experiments demonstrated that plus ends of released MTs grew, paused, or
      shortened while the minus ends were stable or shortened. Microtubule release may
      serve two kinds of cellular function. Release and transport could generate the
      noncentrosomal MT arrays observed in epithelial cells, neurons, and other
      asymmetric, differentiated cells. Release would also contribute to polymer
      turnover by exposing MT minus ends, thereby providing additional sites for loss
      of subunits. The noncentrosomal population of MTs may reflect a steady-state of
      centrosomal nucleation, release, and dynamics.

PMID- 9144192
TI  - Involvement of caspase-dependent activation of cytosolic phospholipase A2 in
      tumor necrosis factor-induced apoptosis.
AB  - Tumor necrosis factor (TNF)-induced apoptosis is mediated by caspases, which are
      cysteine proteases related to interleukin 1beta-converting enzyme. We report here
      that TNF-induced activation of caspases results in the cleavage and activation of
      cytosolic phospholipase A2 (cPLA2) and that activated cPLA2 contributes to
      apoptosis. Inhibition of caspases by expression of a cowpox virus-derived
      inhibitor, CrmA, or by a specific tetrapeptide inhibitor of CPP32/caspase-3,
      acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO), inhibited TNF-induced activation
      of cPLA2 and apoptosis. TNF-induced activation of cPLA2 was accompanied by a
      cleavage of the 100-kDa cPLA2 to a 70-kDa proteolytic fragment. This cleavage was
      inhibited by Ac-DEVD-CHO in a similar manner as that of poly(ADP)ribose
      polymerase, a known substrate of CPP32/caspase-3. Interestingly, specific
      inhibition of cPLA2 enzyme activity by arachidonyl trifluoromethylketone
      (AACOCF3) partially inhibited TNF-induced apoptosis without inhibition of caspase
      activity. Thus, our results suggest a novel caspase-dependent activation pathway
      for cPLA2 during apoptosis and identify cPLA2 as a mediator of TNF-induced cell
      death acting downstream of caspases.

PMID- 9144194
TI  - Mapmodulin: a possible modulator of the interaction of microtubule-associated
      proteins with microtubules.
AB  - We have purified and characterized a 31-kDa protein named mapmodulin that binds
      to the microtubule-associated proteins (MAPs) MAP2, MAP4, and tau. Mapmodulin
      binds free MAPs in strong preference to microtubule-associated MAPs, and appears
      to do so via the MAP's tubulin-binding domain. Mapmodulin inhibits the initial
      rate of MAP2 binding to microtubules, a property that may allow mapmodulin to
      displace MAPs from the path of organelles translocating along microtubules. In
      support of this possibility, mapmodulin stimulates the microtubule- and dynein
      dependent localization of Golgi complexes in semi-intact CHO cells. To our
      knowledge, mapmodulin represents the first example of a protein that can bind and
      potentially regulate multiple MAP proteins.

PMID- 9144195
TI  - Evidence for phosphorylation and oligomeric assembly of presenilin 1.
AB  - Pathogenic mutations in presenilin 1 (PS1) are associated with approximately 50%
      of early-onset familial Alzheimer disease. PS1 is endoproteolytically cleaved to
      yield a 30-kDa N-terminal fragment (NTF) and an 18-kDa C-terminal fragment (CTF).
      Using COS7 cells transfected with human PS1, we have found that phorbol 12, 13
      dibutyrate and forskolin increase the state of phosphorylation of serine residues
      of the human CTF. Phosphorylation of the human CTF resulted in a shift in
      electrophoretic mobility from a single major species of 18 kDa to a doublet of 20
      23 kDa. This mobility shift was also observed with human PS1 that had been
      transfected into mouse neuroblastoma (N2a) cells. Treatment of the phosphorylated
      CTF doublet with phage lambda protein phosphatase eliminated the 20- to 23-kDa
      doublet while enhancing the 18-kDa species, consistent with the interpretation
      that the electrophoretic mobility shift was due to the addition of phosphate to
      the 18-kDa species. The NTF and CTF eluted from a gel filtration column at an
      estimated mass of over 100 kDa, suggesting that these fragments exist as an
      oligomerized species. Upon phosphorylation of the PS1 CTF, the apparent mass of
      the NTF- or CTF-containing oligomers was unchanged. Thus, the association of PS1
      fragments may be maintained during cycles of phosphorylation/dephosphorylation of
      the PS1 CTF.

PMID- 9144196
TI  - The subcellular localization of E2F-4 is cell-cycle dependent.
AB  - The E2F family of transcription factors plays a crucial role in cell cycle
      progression. E2F activity is tightly regulated by a number of mechanisms, which
      include the timely synthesis and degradation of E2F, interaction with
      retinoblastoma protein family members ("pocket proteins"), association with DP
      heterodimeric partner proteins, and phosphorylation of the E2F/DP complex. Here
      we report that another mechanism, subcellular localization, is important for the
      regulation of E2F activity. Unlike E2F-1, -2, or -3, which are constitutively
      nuclear, ectopic E2F-4 and -5 were predominantly cytoplasmic. Cotransfection of
      expression vectors encoding p107, p130, or DP-2, but not DP-1, resulted in the
      nuclear localization of E2F-4 and -5. Moreover, the transcriptional activity of
      E2F-4 was markedly enhanced when it was invariably nuclear. Conversely, it was
      reduced when the protein was excluded from the nucleus, implying that E2F-4
      transcription function depends upon its cytological location. In keeping with
      this, the nuclear/cytoplasmic ratios of endogenous E2F-4 changed as cells exited
      G0, with high ratios in G0 and early G1 and a progressive increase in cytoplasmic
      E2F-4 as cells approached S phase. Thus, the subcellular location of E2F-4 is
      regulated in a cell cycle-dependent manner, providing another potential mechanism
      for its functional regulation.

PMID- 9144197
TI  - A mammalian mitochondrial drug receptor functions as a bacterial "oxygen" sensor.
AB  - The rat mitochondrial outer membrane-localized benzodiazepine receptor (MBR) was
      expressed in wild-type and TspO- (tryptophan-rich sensory protein) strains of the
      facultative photoheterotroph, Rhodobacter sphaeroides 2.4.1, and was shown to
      retain its structure within the bacterial outer membrane as assayed by its
      binding properties with a variety of MBR ligands. Functionally, it was able to
      substitute for TspO by negatively regulating the expression of photosynthesis
      genes in response to oxygen. This effect was reversed pharmacologically with the
      MBR ligand PK11195. These results suggest a close evolutionary and functional
      relationship between the bacterial TspO and the MBR. This relationship provides
      further support for the origin of the mammalian mitochondrion from a
      "photosynthetic" precursor. Finally, these findings provide novel insights into
      the physiological role that has been obscure for the MBR in situ.

PMID- 9144198
TI  - Mitosis in vertebrate somatic cells with two spindles: implications for the
      metaphase/anaphase transition checkpoint and cleavage.
AB  - During mitosis an inhibitory activity associated with unattached kinetochores
      prevents PtK1 cells from entering anaphase until all kinetochores become attached
      to the spindle. To gain a better understanding of how unattached kinetochores
      block the metaphase/anaphase transition we followed mitosis in PtK1 cells
      containing two independent spindles in a common cytoplasm. We found that
      unattached kinetochores on one spindle did not block anaphase onset in a
      neighboring mature metaphase spindle 20 microm away that lacked unattached
      kinetochores. As in cells containing a single spindle, anaphase onset occurred in
      the mature spindles x = 24 min after the last kinetochore attached regardless of
      whether the adjacent immature spindle contained one or more unattached
      kinetochores. These findings reveal that the inhibitory activity associated with
      an unattached kinetochore is functionally limited to the vicinity of the spindle
      containing the unattached kinetochore. We also found that once a mature spindle
      entered anaphase the neighboring spindle also entered anaphase x = 9 min later
      regardless of whether it contained monooriented chromosomes. Thus, anaphase onset
      in the mature spindle catalyzes a "start anaphase" reaction that spreads globally
      throughout the cytoplasm and overrides the inhibitory signal produced by
      unattached kinetochores in an adjacent spindle. Finally, we found that cleavage
      furrows often formed between the two independent spindles. This reveals that the
      presence of chromosomes and/or a spindle between two centrosomes is not a
      prerequisite for cleavage in vertebrate somatic cells.

PMID- 9144199
TI  - Channel formation by antiapoptotic protein Bcl-2.
AB  - Bcl-2 is the prototypical member of a large family of apoptosis-regulating
      proteins, consisting of blockers and promoters of cell death. The three
      dimensional structure of a Bcl-2 homologue, Bcl-XL, suggests striking similarity
      to the pore-forming domains of diphtheria toxin and the bacterial colicins,
      prompting exploration of whether Bcl-2 is capable of forming pores in lipid
      membranes. Using chloride efflux from KCl-loaded unilamellar lipid vesicles as an
      assay, purified recombinant Bcl-2 protein exhibited pore-forming activity with
      properties similar to those of the bacterial toxins, diphtheria toxin, and
      colicins, i.e., dependence on low pH and acidic lipid membranes. In contrast, a
      mutant of Bcl-2 lacking the two core hydrophobic alpha-helices (helices 5 and 6),
      predicted to be required for membrane insertion and channel formation, produced
      only nonspecific effects. In planar lipid bilayers, where detection of single
      channels is possible, Bcl-2 formed discrete ion-conducting, cation-selective
      channels, whereas the Bcl-2 (Deltah5, 6) mutant did not. The most frequent
      conductance observed (18 +/- 2 pS in 0.5 M KCl at pH 7.4) is consistent with a
      four-helix bundle structure arising from Bcl-2 dimers. However, larger channel
      conductances (41 +/- 2 pS and 90 +/- 10 pS) also were detected with progressively
      lower occurrence, implying the step-wise formation of larger oligomers of Bcl-2
      in membranes. These findings thus provide biophysical evidence that Bcl-2 forms
      channels in lipid membranes, suggesting a novel function for this antiapoptotic
      protein.

PMID- 9144200
TI  - Jun NH2-terminal kinase is constitutively activated in T cells transformed by the
      intracellular parasite Theileria parva.
AB  - When T cells become infected by the parasite Theileria parva, they acquire a
      transformed phenotype and no longer require antigen-specific stimulation or
      exogenous growth factors. This is accompanied by constitutive interleukin 2 (IL
      2) and IL-2 receptor expression. Transformation can be reversed entirely by
      elimination of the parasites using the specific drug BW720c. Extracellular signal
      regulated kinase and jun NH2-terminal kinase (JNK) are members of the mitogen
      activated protein kinase family, which play a central role in the regulation of
      cellular differentiation and proliferation and also participate in the regulation
      of IL-2 and IL-2 receptor gene expression. T. parva was found to induce an
      unorthodox pattern of mitogen-activated protein kinase expression in infected T
      cells. JNK-1 and JNK-2 are constitutively active in a parasite-dependent manner,
      but have altered properties. In contrast, extracellular signal-regulated kinase-2
      is not activated even though its activation pathway is functionally intact.
      Different components of the T cell receptor (TCR)-dependent signal transduction
      pathways also were examined. The TCRzeta or CD3epsilon chains were found not to
      be phosphorylated and T. parva-transformed T cells were resistant to inhibitors
      that block the early steps of T cell activation. Compounds that inhibit the
      progression of T cells to proliferation, however, were inhibitory. Our data
      provide the first example, to our knowledge, for parasite-mediated JNK
      activation, and our findings strongly suggest that T. parva not only lifts the
      requirement for antigenic stimulation but also entirely bypasses early TCR
      dependent signal transduction pathways to induce continuous proliferation.

PMID- 9144201
TI  - Functional growth hormone (GH) receptors and GH are expressed by preimplantation
      mouse embryos: a role for GH in early embryogenesis?
AB  - The results of this study challenge the widely held view that growth hormone (GH)
      acts only during the postnatal period. RNA phenotyping shows transcripts for the
      GH receptor and GH-binding protein in mouse preimplantation embryos of all stages
      from fertilized eggs (day 1) to blastocysts (day 4). An antibody specific to the
      cytoplasmic region of the GH receptor revealed receptor protein expression, first
      in two-cell embryos, the stage of activation of the embryonic genome (day 2), and
      in all subsequent stages. In cleavage-stage embryos this immunoreactivity was
      localized mainly to the nucleus, but clear evidence of membrane labeling was
      apparent in blastocysts. GH receptor immunoreactivity was also observed in
      cumulus cells associated with unfertilized oocytes but not in the unfertilized
      oocytes. The blastocyst receptor was demonstrated to be functional, exhibiting
      the classic bell-shaped dose-response curves for GH stimulation of both 3-O
      methyl glucose transport and protein synthesis. Maximal stimulation of 40-50% was
      seen for both responses at less than 1 ng/ml recombinant GH, suggesting a role
      for maternal GH. However mRNA transcripts for GH were also detected from the
      morula stage (day 3) by using reverse transcription-PCR, and GH immunoreactivity
      was seen in blastocysts. These observations raise the possibility of a
      paracrine/autocrine GH loop regulating embryonic development in its earliest
      stages.

PMID- 9144202
TI  - Cooperative functions of the reaper and head involution defective genes in the
      programmed cell death of Drosophila central nervous system midline cells.
AB  - In Drosophila, the chromosomal region 75C1-2 contains at least three genes,
      reaper (rpr), head involution defective (hid), and grim, that have important
      functions in the activation of programmed cell death. To better understand how
      cells are killed by these genes, we have utilized a well defined set of embryonic
      central nervous system midline cells that normally exhibit a specific pattern of
      glial cell death. In this study we show that both rpr and hid are expressed in
      dying midline cells and that the normal pattern of midline cell death requires
      the function of multiple genes in the 75C1-2 interval. We also utilized the
      P[UAS]/P[Gal4] system to target expression of rpr and hid to midline cells.
      Targeted expression of rpr or hid alone was not sufficient to induce ectopic
      midline cell death. However, expression of both rpr and hid together rapidly
      induced ectopic midline cell death that resulted in axon scaffold defects
      characteristic of mutants with abnormal midline cell development. Midline
      targeted expression of the baculovirus p35 protein, a caspase inhibitor, blocked
      both normal and ectopic rpr- and hid-induced cell death. Taken together, our
      results suggest that rpr and hid are expressed together and cooperate to induce
      programmed cell death during development of the central nervous system midline.

PMID- 9144203
TI  - Phenotypic alterations in insulin-deficient mutant mice.
AB  - Two mouse insulin genes, Ins1 and Ins2, were disrupted and lacZ was inserted at
      the Ins2 locus by gene targeting. Double nullizygous insulin-deficient pups were
      growth-retarded. They did not show any glycosuria at birth but soon after
      suckling developed diabetes mellitus with ketoacidosis and liver steatosis and
      died within 48 h. Interestingly, insulin deficiency did not preclude pancreas
      organogenesis and the appearance of the various cell types of the endocrine
      pancreas. The presence of lacZ expressing beta cells and glucagon-positive alpha
      cells was demonstrated by cytochemistry and immunocytochemistry. Reverse
      transcription-coupled PCR analysis showed that somatostatin and pancreatic
      polypeptide mRNAs were present, although at reduced levels, accounting for the
      presence also of delta and pancreatic polypeptide cells, respectively.
      Morphometric analysis revealed enlarged islets of Langherans in the pancreas from
      insulin-deficient pups, suggesting that insulin might function as a negative
      regulator of islet cell growth. Whether insulin controls the growth of specific
      islet cell types and the molecular basis for this action remain to be elucidated.

PMID- 9144205
TI  - Population regulation in snowshoe hare and Canadian lynx: asymmetric food web
      configurations between hare and lynx.
AB  - The snowshoe hare and the Canadian lynx in the boreal forests of North America
      show 9- to 11-year density cycles. These are generally assumed to be linked to
      each other because lynx are specialist predators on hares. Based on time series
      data for hare and lynx, we show that the dominant dimensional structure of the
      hare series appears to be three whereas that of the lynx is two. The three
      dimensional structure of the hare time series is hypothesized to be due to a
      three-trophic level model in which the hare may be seen as simultaneously
      regulated from below and above. The plant species in the hare diet appear
      compensatory to one another, and the predator species may, likewise, be seen as
      an internally compensatory guild. The lynx time series are, in contrast,
      consistent with a model of donor control in which their populations are regulated
      from below by prey availability. Thus our analysis suggests that the classic view
      of a symmetric hare-lynx interaction is too simplistic. Specifically, we argue
      that the classic food chain structure is inappropriate: the hare is influenced by
      many predators other than the lynx, and the lynx is primarily influenced by the
      snowshoe hare.

PMID- 9144204
TI  - Ligand-dependent development of the endothelial and hemopoietic lineages from
      embryonic mesodermal cells expressing vascular endothelial growth factor receptor
      2.
AB  - The existence of a common precursor for endothelial and hemopoietic cells, termed
      the hemangioblast, has been postulated since the beginning of the century.
      Recently, deletion of the endothelial-specific vascular endothelial growth factor
      receptor 2 (VEGFR2) by gene targeting has shown that both endothelial and
      hemopoietic cells are absent in homozygous null mice. This observation suggested
      that VEGFR2 could be expressed by the hemangioblast and essential for its further
      differentiation along both lineages. However, it was not possible to exclude the
      hypothesis that hemopoietic failure was a secondary effect resulting from the
      absence of an endothelial cell microenvironment. To distinguish between these two
      hypotheses, we have produced a mAb directed against the extracellular domain of
      avian VEGFR2 and isolated VEGFR2+ cells from the mesoderm of chicken embryos at
      the gastrulation stage. We have found that in clonal cultures, a VEGFR2+ cell
      gives rise to either a hemopoietic or an endothelial cell colony. The
      developmental decision appears to be regulated by the binding of two different
      VEGFR2 ligands. Thus, endothelial differentiation requires VEGF, whereas
      hemopoietic differentiation occurs in the absence of VEGF and is significantly
      reduced by soluble VEGFR2, showing that this process could be mediated by a
      second, yet unidentified, VEGFR2 ligand. These observations thus suggest strongly
      that in the absence of the VEGFR2 gene product, the precursors of both
      hemopoietic and vascular endothelial lineages cannot survive. These cells
      therefore might be the initial targets of the VEGFR2 null mutation.

PMID- 9144207
TI  - Evolution of paired domains: isolation and sequencing of jellyfish and hydra Pax
      genes related to Pax-5 and Pax-6.
AB  - Pax proteins are a family of transcription factors with a highly conserved paired
      domain; many members also contain a paired-type homeodomain and/or an
      octapeptide. Nine mammalian Pax genes are known and classified into four
      subgroups: Pax-1/9, Pax-2/5/8, Pax-3/7, and Pax-4/6. Most of these genes are
      involved in nervous system development. In particular, Pax-6 is a key regulator
      that controls eye development in vertebrates and Drosophila. Although the Pax-4/6
      subgroup seems to be more closely related to Pax-2/5/8 than to Pax-3/7 or Pax
      1/9, its evolutionary origin is unknown. We therefore searched for a Pax-6
      homolog and related genes in Cnidaria, which is the lowest phylum of animals that
      possess a nervous system and eyes. A sea nettle (a jellyfish) genomic library was
      constructed and two pax genes (Pax-A and -B) were isolated and partially
      sequenced. Surprisingly, unlike most known Pax genes, the paired box in these two
      genes contains no intron. In addition, the complete cDNA sequences of hydra Pax-A
      and -B were obtained. Hydra Pax-B contains both the homeodomain and the
      octapeptide, whereas hydra Pax-A contains neither. DNA binding assays showed that
      sea nettle Pax-A and -B and hydra Pax-A paired domains bound to a Pax-5/6 site
      and a Pax-5 site, although hydra Pax-B paired domain bound neither. An alignment
      of all available paired domain sequences revealed two highly conserved regions,
      which cover the DNA binding contact positions. Phylogenetic analysis showed that
      Pax-A and especially Pax-B were more closely related to Pax-2/5/8 and Pax-4/6
      than to Pax-1/9 or Pax-3/7 and that the Pax genes can be classified into two
      supergroups: Pax-A/Pax-B/Pax-2/5/8/4/6 and Pax-1/9/3/7. From this analysis and
      the gene structure, we propose that modern Pax-4/6 and Pax-2/5/8 genes evolved
      from an ancestral gene similar to cnidarian Pax-B, having both the homeodomain
      and the octapeptide.

PMID- 9144208
TI  - The origin and evolution of animal appendages.
AB  - Animals have evolved diverse appendages adapted for locomotion, feeding and other
      functions. The genetics underlying appendage formation are best understood in
      insects and vertebrates. The expression of the Distal-less (Dll) homeoprotein
      during arthropod limb outgrowth and of Dll orthologs (Dlx) in fish fin and
      tetrapod limb buds led us to examine whether expression of this regulatory gene
      may be a general feature of appendage formation in protostomes and deuterostomes.
      We find that Dll is expressed along the proximodistal axis of developing
      polychaete annelid parapodia, onychophoran lobopodia, ascidian ampullae, and even
      echinoderm tube feet. Dll/Dlx expression in such diverse appendages in these six
      coelomate phyla could be convergent, but this would have required the independent
      co-option of Dll/Dlx several times in evolution. It appears more likely that
      ectodermal Dll/Dlx expression along proximodistal axes originated once in a
      common ancestor and has been used subsequently to pattern body wall outgrowths in
      a variety of organisms. We suggest that this pre-Cambrian ancestor of most
      protostomes and the deuterostomes possessed elements of the genetic machinery for
      and may have even borne appendages.

PMID- 9144209
TI  - Population dynamics, demographic stochasticity, and the evolution of cooperation.
AB  - A basic evolutionary problem posed by the Iterated Prisoner's Dilemma game is to
      understand when the paradigmatic cooperative strategy Tit-for-Tat can invade a
      population of pure defectors. Deterministically, this is impossible. We consider
      the role of demographic stochasticity by embedding the Iterated Prisoner's
      Dilemma into a population dynamic framework. Tit-for-Tat can invade a population
      of defectors when their dynamics exhibit short episodes of high population
      densities with subsequent crashes and long low density periods with strong
      genetic drift. Such dynamics tend to have reddened power spectra and temporal
      distributions of population size that are asymmetric and skewed toward low
      densities. The results indicate that ecological dynamics are important for
      evolutionary shifts between adaptive peaks.

PMID- 9144210
TI  - A natural classification of the basic helix-loop-helix class of transcription
      factors.
AB  - A natural (evolutionary) classification is provided for 242 basic helix-loop
      helix (bHLH) motif-containing proteins. Phylogenetic analyses of amino acid
      sequences describe the patterns of evolutionary change within the motif and
      delimit evolutionary lineages. These evolutionary lineages represent well known
      functional groups of proteins and can be further arranged into five groups based
      on binding to DNA at the hexanucleotide E-box, the amino acid patterns in other
      components of the motif, and the presence/absence of a leucine zipper. The
      hypothesized ancestral amino acid sequence for the bHLH transcription factor
      family is given together with the ancestral sequences of the subgroups. It is
      suggested that bHLH proteins containing a leucine zipper are not a natural,
      monophyletic group.

PMID- 9144211
TI  - Molecular origin of the mosaic sequence arrangements of higher primate alpha
      globin duplication units.
AB  - The human adult alpha-globin locus consists of three pairs of homology blocks (X,
      Y, and Z) interspersed with three nonhomology blocks (I, II, and III), and three
      Alu family repeats, Alu1, Alu2, and Alu3. It has been suggested that an ancient
      primate alpha-globin-containing unit was ancestral to the X, Y, and Z and the
      Alu1/Alu2 repeats. However, the evolutionary origin of the three nonhomologous
      blocks has remained obscure. We have now analyzed the sequence organization of
      the entire adult alpha-globin locus of gibbon (Hylobates lar). DNA segments
      homologous to human block I occur in both duplication units of the gibbon alpha
      globin locus. Detailed interspecies sequence comparisons suggest that
      nonhomologous blocks I and II, as well as another sequence, IV, were all part of
      the ancestral alpha-globin-containing unit prior to its tandem duplication.
      However, sometime thereafter, block I was deleted from the human alpha1-globin
      containing unit, and block II was also deleted from the alpha2-globin-containing
      unit in both human and gibbon. These were probably independent events both
      mediated by independent illegitimate recombination processes. Interestingly, the
      end points of these deletions coincide with potential insertion sites of Alu
      family repeats. These results suggest that the shaping of DNA segments in
      eukaryotic genomes involved the retroposition of repetitive DNA elements in
      conjunction with simple DNA recombination processes.

PMID- 9144212
TI  - Four primordial modes of tRNA-synthetase recognition, determined by the (G,C)
      operational code.
AB  - In distinction to single-stranded anticodons built of G, C, A, and U bases, their
      presumable double-stranded precursors at the first three positions of the
      acceptor stem are composed almost invariably of G-C and C-G base pairs. Thus, the
      "second" operational RNA code responsible for correct aminoacylation seems to be
      a (G,C) code preceding the classic genetic code. Although historically rooted,
      the two codes were destined to diverge quite early. However, closer inspection
      revealed that two complementary catalytic domains of class I and class II
      aminoacyl-tRNA synthetases (aaRSs) multiplied by two, also complementary, G2-C71
      and C2-G71 targets in tRNA acceptors, yield four (2 x 2) different modes of
      recognition. It appears therefore that the core four-column organization of the
      genetic code, associated with the most conservative central base of anticodons
      and codons, was in essence predetermined by these four recognition modes of the
      (G,C) operational code. The general conclusion follows that the genetic code per
      se looks like a "frozen accident" but only beyond the "2 x 2 = 4" scope. The four
      primordial modes of tRNA-aaRS recognition are amenable to direct experimental
      verification.

PMID- 9144213
TI  - An essential cell division gene of Drosophila, absent from Saccharomyces, encodes
      an unusual protein with tubulin-like and myosin-like peptide motifs.
AB  - Null mutations at the misato locus of Drosophila melanogaster are associated with
      irregular chromosomal segregation at cell division. The consequences for
      morphogenesis are that mutant larvae are almost devoid of imaginal disk tissue,
      have a reduction in brain size, and die before the late third-instar larval
      stage. To analyze these findings, we isolated cDNAs in and around the misato
      locus, mapped the breakpoints of chromosomal deficiencies, determined which
      transcript corresponded to the misato gene, rescued the cell division defects in
      transgenic organisms, and sequenced the genomic DNA. Database searches revealed
      that misato codes for a novel protein, the N-terminal half of which contains a
      mixture of peptide motifs found in alpha-, beta-, and gamma-tubulins, as well as
      a motif related to part of the myosin heavy chain proteins. The sequence
      characteristics of misato indicate either that it arose from an ancestral tubulin
      like gene, different parts of which underwent convergent evolution to resemble
      motifs in the conventional tubulins, or that it arose by the capture of motifs
      from different tubulin genes. The Saccharomyces cerevisiae genome lacks a true
      homolog of the misato gene, and this finding highlights the emerging problem of
      assigning functional attributes to orphan genes that occur only in some
      evolutionary lineages.

PMID- 9144214
TI  - P element insertion-dependent gene activation in the Drosophila eye.
AB  - Insights into the function of a gene can be gained in multiple ways, including
      loss-of-function phenotype, sequence similarity, expression pattern, and by the
      consequences of its misexpression. Analysis of the phenotypes produced by
      expression of a gene at an abnormal time, place, or level may provide clues to a
      gene's function when other approaches are not illuminating. Here we report that
      an eye-specific, enhancer-promoter present in the P element expression vector
      pGMR is able to drive high level expression in the eye of genes near the site of
      P element insertion. Cell fate determination, differentiation, proliferation, and
      death are essential for normal eye development. Thus the ability to carry out eye
      specific misexpression of a significant fraction of genes in the genome, given
      the dispensability of the eye for viability and fertility of the adult, should
      provide a powerful approach for identifying regulators of these processes. To
      test this idea we carried out two overexpression screens for genes that function
      to regulate cell death. We screened for insertion-dependent dominant phenotypes
      in a wild-type background, and for dominant modifiers of a reaper overexpression
      induced small eye phenotype. Multiple chromosomal loci were identified, including
      an insertion 5' to hid, a potent inducer of apoptosis, and insertions 5' to
      DIAP1, a cell death suppressor. To facilitate the cloning of genes near the P
      element insertion new misexpression vectors were created. A screen with one of
      these vectors identified eagle as a suppressor of a rough eye phenotype
      associated with overexpression of an activated Ras1 gene.

PMID- 9144215
TI  - The p20 and Ded1 proteins have antagonistic roles in eIF4E-dependent translation
      in Saccharomyces cerevisiae.
AB  - The translation initiation factor eIF4E mediates the binding of the small
      ribosomal subunit to the cap structure at the 5' end of the mRNA. In
      Saccharomyces cerevisiae, the cap-binding protein eIF4E is mainly associated with
      eIF4G, forming the cap-binding complex eIF4F. Other proteins are detected upon
      purification of the complex on cap-affinity columns. Among them is p20, a protein
      of unknown function encoded by the CAF20 gene. Here, we show a negative
      regulatory role for the p20 protein in translation initiation. Deletion of CAF20
      partially suppresses mutations in translation initiation factors. Overexpression
      of the p20 protein results in a synthetic enhancement of translation mutation
      phenotypes. Similar effects are observed for mutations in the DED1 gene, which we
      have isolated as a multicopy suppressor of a temperature-sensitive eIF4E
      mutation. The DED1 gene encodes a putative RNA helicase of the DEAD-box family.
      The analyses of its suppressor activity, of polysome profiles of ded1 mutant
      strains, and of synthetic lethal interactions with different translation mutants
      indicate that the Ded1 protein has a role in translation initiation in S.
      cerevisiae.

PMID- 9144216
TI  - Functional domains are specified to single-cell resolution in a Drosophila
      epithelium.
AB  - Specification of pattern is fundamental to the development of a multicellular
      organism. The Malpighian (renal) tubule of Drosophila melanogaster is a simple
      epithelium that proliferates under the direction of a single tip cell into three
      morphologically distinct domains. However, systematic analysis of a panel of over
      700 P[GAL4] enhancer trap lines reveals unexpected richness for such an
      apparently simple tissue. Using numerical analysis, it was possible formally to
      reconcile apparently similar or complementary expression domains and thus to
      define at least five genetically defined domains and multiple cell types.
      Remarkably, the positions of domain boundaries and the numbers of both principal
      and secondary ("stellate") cell types within each domain are reproducible to near
      single-cell precision between individual animals. Domains of physiological
      function were also mapped using transport or expression assays. Invariably, they
      respect the boundaries defined by enhancer activity. These genetic domains can
      also be visualized in vivo, both in transgenic and wild-type flies, providing an
      "identified cell" system for epithelial physiology. Building upon recent advances
      in Drosophila Malpighian tubule physiology, the present study confirms this
      tissue as a singular model for integrative physiology.

PMID- 9144217
TI  - Clustering of meiotic double-strand breaks on yeast chromosome III.
AB  - In the yeast Saccharomyces cerevisiae, meiotic recombination is initiated by
      transient DNA double-strand breaks (DSBs) that are repaired by interaction of the
      broken chromosome with its homologue. To identify a large number of DSB sites and
      gain insight into the control of DSB formation at both the local and the whole
      chromosomal levels, we have determined at high resolution the distribution of
      meiotic DSBs along the 340 kb of chromosome III. We have found 76 DSB regions,
      mostly located in intergenic promoter-containing intervals. The frequency of DSBs
      varies at least 50-fold from one region to another. The global distribution of
      DSB regions along chromosome III is nonrandom, defining large (39-105 kb)
      chromosomal domains, both hot and cold. The distribution of these localized DSBs
      indicates that they are likely to initiate most crossovers along chromosome III,
      but some discrepancies remain to be explained.

PMID- 9144218
TI  - An enhancer-blocking element between alpha and delta gene segments within the
      human T cell receptor alpha/delta locus.
AB  - T cell receptor (TCR) alpha and delta gene segments are organized within a single
      genetic locus but are differentially regulated during T cell development. An
      enhancer-blocking element (BEAD-1, for blocking element alpha/delta 1) was
      localized to a 2.0-kb region 3' of TCR delta gene segments and 5' of TCR alpha
      joining gene segments within this locus. BEAD-1 blocked the ability of the TCR
      delta enhancer (Edelta) to activate a promoter when located between the two in a
      chromatin-integrated construct. We propose that BEAD-1 functions as a boundary
      that separates the TCR alpha/delta locus into distinct regulatory domains
      controlled by Edelta and the TCR alpha enhancer, and that it prevents Edelta from
      opening the chromatin of the TCR alpha joining gene segments for VDJ
      recombination at an early stage of T cell development.

PMID- 9144219
TI  - Multiple-complete-digest restriction fragment mapping: generating sequence-ready
      maps for large-scale DNA sequencing.
AB  - Multiple-complete-digest mapping is a DNA mapping technique based on complete
      restriction-digest fingerprints of a set of clones that provides highly redundant
      coverage of the mapping target. The maps assembled from these fingerprints order
      both the clones and the restriction fragments. Maps are coordinated across three
      enzymes in the examples presented. Starting with yeast artificial chromosome
      contigs from the 7q31.3 and 7p14 regions of the human genome, we have produced
      cosmid-based maps spanning more than one million base pairs. Each yeast
      artificial chromosome is first subcloned into cosmids at a redundancy of x15-30.
      Complete-digest fragments are electrophoresed on agarose gels, poststained, and
      imaged on a fluorescent scanner. Aberrant clones that are not representative of
      the underlying genome are rejected in the map construction process. Almost every
      restriction fragment is ordered, allowing selection of minimal tiling paths with
      clone-to-clone overlaps of only a few thousand base pairs. These maps demonstrate
      the practicality of applying the experimental and software-based steps in
      multiple-complete-digest mapping to a target of significant size and complexity.
      We present evidence that the maps are sufficiently accurate to validate both the
      clones selected for sequencing and the sequence assemblies obtained once these
      clones have been sequenced by a "shotgun" method.

PMID- 9144220
TI  - Genome scan for teratogen-induced clefting susceptibility loci in the mouse:
      evidence of both allelic and locus heterogeneity distinguishing cleft lip and
      cleft palate.
AB  - Nonsyndromic clefting of the lip and palate in humans has a highly complex
      etiology, with both multiple genetic loci and exposure to teratogens influencing
      susceptibility. Previous studies using mouse models have examined only very small
      portions of the genome. Here we report the findings of a genome-wide search for
      susceptibility genes for teratogen-induced clefting in the AXB and BXA set of
      recombinant inbred mouse strains. We compare results obtained using phenytoin
      (which induces cleft lip) and 6-aminonicotinamide (which induces cleft palate).
      We use a new statistical approach based on logistic regression suitable for these
      categorical data to identify several chromosomal regions as possible locations of
      clefting susceptibility loci, and we review candidate genes located within each
      region. Because cleft lip and cleft palate do not frequently co-aggregate in
      human families and because these structures arise semi-independently during
      development, these disorders are usually considered to be distinct in etiology.
      Our data, however, implicate several of the same chromosomal regions for both
      forms of clefting when teratogen-induced. Furthermore, different parental strain
      alleles are usually associated with clefting of the lip versus that of the palate
      (i.e., allelic heterogeneity). Because several other chromosomal regions are
      associated with only one form of clefting, locus heterogeneity also appears to be
      involved. Our findings in this mouse model suggest several priority areas for
      evaluation in human epidemiological studies.

PMID- 9144221
TI  - Characteristic enrichment of DNA repeats in different genomes.
AB  - Using computer programs developed for this purpose, we searched for various
      repeated sequences including inverted, direct tandem, and homopurine
      homopyrimidine mirror repeats in various prokaryotes, eukaryotes, and an
      archaebacterium. Comparison of observed frequencies with expectations revealed
      that in bacterial genomes and organelles the frequency of different repeats is
      either random or enriched for inverted and/or direct tandem repeats. By contrast,
      in all eukaryotic genomes studied, we observed an overrepresentation of all
      repeats, especially homopurine-homopyrimidine mirror repeats. Analysis of the
      genomic distribution of all abundant repeats showed that they are virtually
      excluded from coding sequences. Unexpectedly, the frequencies of abundant repeats
      normalized for their expectations were almost perfect exponential functions of
      their size, and for a given repeat this function was indistinguishable between
      different genomes.

PMID- 9144222
TI  - Identification of nitric oxide synthase as a protective locus against
      tuberculosis.
AB  - Mutagenesis of the host immune system has helped identify response pathways
      necessary to combat tuberculosis. Several such pathways may function as
      activators of a common protective gene: inducible nitric oxide synthase (NOS2).
      Here we provide direct evidence for this gene controlling primary Mycobacterium
      tuberculosis infection using mice homozygous for a disrupted NOS2 allele. NOS2(-/
      ) mice proved highly susceptible, resembling wild-type littermates
      immunosuppressed by high-dose glucocorticoids, and allowed Mycobacterium
      tuberculosis to replicate faster in the lungs than reported for other gene
      deficient hosts. Susceptibility appeared to be independent of the only known
      naturally inherited antimicrobial locus, NRAMP1. Progression of chronic
      tuberculosis in wild-type mice was accelerated by specifically inhibiting NOS2
      via administration of N6-(1-iminoethyl)-L-lysine. Together these findings
      identify NOS2 as a critical host gene for tuberculostasis.

PMID- 9144223
TI  - The alpha1 domain of HLA-G1 and HLA-G2 inhibits cytotoxicity induced by natural
      killer cells: is HLA-G the public ligand for natural killer cell inhibitory
      receptors?
AB  - We have investigated the protective role of the membrane-bound HLA-G1 and HLA-G2
      isoforms against natural killer (NK) cell cytotoxicity. For this purpose, HLA-G1
      and HLA-G2 cDNAs were transfected into the HLA class I-negative human K562 cell
      line, a known reference target for NK lysis. The HLA-G1 protein, encoded by a
      full-length mRNA, presents a structure similar to that of classical HLA class I
      antigens. The HLA-G2 protein, deduced from an alternatively spliced transcript,
      consists of the alpha1 domain linked to the alpha3 domain. In this study we
      demonstrate that (i) HLA-G2 is present at the cell surface as a truncated class I
      molecule associated with beta2-microglobulin; (ii) NK cytolysis, observed in
      peripheral blood mononuclear cells and in polyclonal CD3(-) CD16(+) CD56(+) NK
      cells obtained from 20 donors, is inhibited by both HLA-G1 and HLA-G2; this HLA-G
      mediated inhibition is reversed by blocking HLA-G with a specific mAb; this led
      us to the conjecture that HLA-G is the public ligand for NK inhibitory receptors
      (NKIR) present in all individuals; (iii) the alpha1 domain common to HLA-G1 and
      HLA-G2 could mediate this protection from NK lysis; and (iv) when transfected
      into the K562 cell line, both HLA-G1 and HLA-G2 abolish lysis by the T cell
      leukemia NK-like YT2C2 clone due to interaction between the HLA-G isoform on the
      target cell surface and a membrane receptor on YT2C2. Because NKIR1 and NKIR2,
      known to interact with HLA-G, were undetectable on YT2C2, we conclude that a yet
      unknown specific receptor for HLA-G1 and HLA-G2 is present on these cells.

PMID- 9144224
TI  - The inhibition of antigen-presenting activity of dendritic cells resulting from
      UV irradiation of murine skin is restored by in vitro photorepair of cyclobutane
      pyrimidine dimers.
AB  - Exposing skin to UVB (280-320 nm) radiation suppresses contact hypersensitivity
      by a mechanism that involves an alteration in the activity of cutaneous antigen
      presenting cells (APC). UV-induced DNA damage appears to be an important
      molecular trigger for this effect. The specific target cells in the skin that
      sustain DNA damage relevant to the immunosuppressive effect have yet to be
      identified. We tested the hypothesis that UV-induced DNA damage in the cutaneous
      APC was responsible for their impaired ability to present antigen after in vivo
      UV irradiation. Cutaneous APC were collected from the draining lymph nodes of UVB
      irradiated, hapten-sensitized mice and incubated in vitro with liposomes
      containing a photolyase (Photosomes; Applied Genetics, Freeport, NY), which, upon
      absorption of photoreactivating light, splits UV-induced cyclobutane pyrimidine
      dimers. Photosome treatment followed by photoreactivating light reduced the
      number of dimer-containing APC, restored the in vivo antigen-presenting activity
      of the draining lymph node cells, and blocked the induction of suppressor T
      cells. Neither Photosomes nor photoreactivating light alone, nor
      photoreactivating light given before Photosomes, restored APC activity, and
      Photosome treatment did not reverse the impairment of APC function when
      isopsoralen plus UVA (320-400 nm) radiation was used instead of UVB. These
      controls indicate that the restoration of APC function matched the requirements
      of Photosome-mediated DNA repair for dimers and post-treatment photoreactivating
      light. These results provide compelling evidence that it is UV-induced DNA damage
      in cutaneous APC that leads to reduced immune function.

PMID- 9144225
TI  - A novel pair of immunoglobulin-like receptors expressed by B cells and myeloid
      cells.
AB  - An Fcalpha receptor probe of human origin was used to identify novel members of
      the Ig gene superfamily in mice. Paired Ig-like receptors, named PIR-A and PIR-B,
      are predicted from sequence analysis of the cDNAs isolated from a mouse splenic
      library. Both type I transmembrane proteins possess similar ectodomains with six
      Ig-like loops, but have different transmembrane and cytoplasmic regions. The
      predicted PIR-A protein has a short cytoplasmic tail and a charged Arg residue in
      the transmembrane region that, by analogy with the FcalphaR relative, suggests
      the potential for association with an additional transmembrane protein to form a
      signal transducing unit. In contrast, the PIR-B protein has an uncharged
      transmembrane region and a long cytoplasmic tail containing four potential
      immunoreceptor tyrosine-based inhibitory motifs. These features are shared by the
      related killer inhibitory receptors. PIR-A proteins appear to be highly variable,
      in that predicted peptide sequences differ for seven randomly selected PIR-A
      clones, whereas PIR-B cDNA clones are invariant. Southern blot analysis with PIR
      B and PIR-A-specific probes suggests only one PIR-B gene and multiple PIR-A
      genes. The PIR-A and PIR-B genes are expressed in B lymphocytes and myeloid
      lineage cells, wherein both are expressed simultaneously. The characteristics of
      the highly-conserved PIR-A and PIR-B genes and their coordinate cellular
      expression suggest a potential regulatory role in humoral, inflammatory, and
      allergic responses.

PMID- 9144226
TI  - A nontoxic mutant of cholera toxin elicits Th2-type responses for enhanced
      mucosal immunity.
AB  - We have characterized a nontoxic mutant of cholera toxin (CT) as a mucosal
      adjuvant in mice. The mutant CT was made by substitution of serine with
      phenylalanine at position 61 of the A subunit (S61F), which resulted in loss of
      ADP ribosyltransferase activity and toxicity. Mice were intranasally immunized
      with ovalbumin, tetanus toxoid, or influenza virus either alone or together with
      mutant CT S61F, native CT, or recombinant CT-B. Mice immunized with these
      proteins plus S61F showed high serum titers of protein-specific IgG and IgA
      antibodies that were comparable to those induced by native CT. Further, high
      protein-specific IgA antibody responses were observed in nasal and vaginal
      washes, saliva, and fecal extracts as well as increased numbers of IgG and IgA
      antibody forming cells in cervical lymph nodes and lung tissues of mice
      intranasally immunized with these proteins and S61F or native CT, but not with
      recombinant CT-B or protein alone. Both S61F and native CT enhanced the induction
      of ovalbumin-specific CD4(+) T cells in lung and splenic tissues, and these T
      cells produced a Th2-type cytokine pattern of interleukin 4 (IL-4), IL-5, IL-6,
      and IL-10 as determined by analysis of secreted proteins and by quantitation of
      cytokine-specific mRNA. These results have shown that mutant CT S61F is an
      effective mucosal adjuvant when administrated intranasally and induces mucosal
      and systemic antibody responses which are mediated by CD4(+) Th2-type cells.

PMID- 9144227
TI  - Molecular cloning, sequence, expression, and processing of the interleukin 16
      precursor.
AB  - Interleukin 16 (IL-16) has been shown to function as chemoattractant factor, as a
      modulator of T-cell activation, and as an inhibitor of immunodeficiency virus
      replication. The recent identification of inconsistencies in published IL-16 cDNA
      nucleotide sequences led to the proposal that IL-16 is synthesized in the form of
      a large precursor protein (pro-IL-16). To identify the true transcriptional start
      of the IL-16 mRNA rapid amplification of cDNA ends methods were applied. The
      complete pro-IL-16 cDNA was subsequently molecularly cloned, sequenced, and
      expressed in COS-7 cells. We report here that pro-IL-16 is most likely
      synthesized as a 67-kDa protein and is encoded from a major 2.6-kb transcript.
      Recombinant pro-IL-16 polypeptides are specifically cleaved in lysates of CD8(+)
      cells, suggesting that the naturally secreted bioactive form of IL-16 is smaller
      than the originally published 130 amino acids fragment. Moreover, in contrast to
      other interleukins such as IL-15, IL-16 mRNA expression is almost exclusively
      limited to lymphatic tissues underlining the potential of IL-16 as an immune
      regulatory molecule.

PMID- 9144228
TI  - High-affinity binding of bioactive glycosylation-inhibiting factor to antigen
      primed T cells and natural killer cells.
AB  - High-affinity binding was demonstrated between suppressor-T-cell-derived
      bioactive glycosylation-inhibiting factor (GIF) and helper T hybridomas and
      natural killer cell line cells. Inactive GIF present in cytosol of suppressor T
      cells and Escherichia coli-derived recombinant human GIF (rhGIF) failed to bind
      to these cells. However, affinity of rhGIF for the target cells was generated by
      replacement of Cys-57 in the sequence with Ala or of Asn-106 with Ser or binding
      of 5-thio-2-nitrobenzoic acid to Cys-60 in the molecule. Such mutations and the
      chemical modification of rhGIF synergistically increased the affinity of GIF
      molecules for the target cells. The results indicated that receptors on the
      target cells recognize conformational structures of bioactive GIF. Equilibrium
      dissociation constant (Kd) of the specific binding between bioactive rGIF
      derivatives and high-affinity receptors was 10-100 pM. Receptors for bioactive
      GIF derivatives were detected on Th1 and Th2 T helper clones and natural killer
      NK1.1(+) cells in normal spleen but not on naive T or B cells. Neither the
      inactive rGIF nor bioactive rGIF derivatives bound to macrophage and monocyte
      lines or induced macrophages for tumor necrosis factor alpha production.

PMID- 9144229
TI  - Sequence dependent hypermutation of the immunoglobulin heavy chain in cultured B
      cells.
AB  - The variable (V) regions of immunoglobulin heavy and light chains undergo high
      rates of somatic mutation during the immune response. Although point mutations
      accumulate throughout the V regions and their immediate flanking sequences,
      analysis of large numbers of mutations that have arisen in vivo reveal that the
      triplet AGC appears to be most susceptible to mutation. We have stably
      transfected B cell lines with gamma2a heavy chain constructs containing TAG
      nonsense codons in their V regions that are part of either a putative (T)AGC hot
      spot or a (T)AGA non-hot spot motif. Using an ELISA spot assay to detect
      revertants and fluctuation analysis to determine rates of mutation, the rate of
      reversion of the TAG nonsense codon has been determined for different motifs in
      different parts of the V region. In the NSO plasma cell line, the (T)AGC hot spot
      motif mutates at rates of approximately 6 x 10(-4)/bp per generation and
      approximately 3 x 10(-5)/bp per generation at residues 38 and 94 in the V region.
      At each of these locations, the (T)AGC hot spot motif is 20-30 times more likely
      to undergo mutation than the (T)AGA non-hot spot motif. Moreover, the AGA non-hot
      spot motif mutates at as high a rate as the hot spot motif when it is located
      adjacent to hot spot motifs, suggesting that more extended sequences influence
      susceptibility to mutation.

PMID- 9144230
TI  - Prevention of autoimmune disease due to lymphocyte modulation by the B-subunit of
      Escherichia coli heat-labile enterotoxin.
AB  - We demonstrate that the receptor binding moiety of Escherichia coli heat-labile
      enterotoxin (EtxB) can completely prevent autoimmune disease in a murine model of
      arthritis. Injection of male DBA/1 mice at the base of the tail with type II
      collagen in the presence of complete Freund's adjuvant normally leads to
      arthritis, as evidenced by inflammatory infiltration and swelling of the joints.
      A separate injection of EtxB at the same time as collagen challenge prevented
      leukocyte infiltration, synovial hyperplasia, and degeneration of the articular
      cartilage and reduced clinical symptoms of disease by 82%. The principle
      biological property of EtxB is its ability to bind to the ubiquitous cell surface
      receptor GM1 ganglioside, and to other galactose-containing glycolipids and
      galactoproteins. The importance of receptor interaction in mediating protection
      from arthritis was demonstrated by the failure of a non-receptor-binding mutant
      of EtxB to elicit any protective effect. Analysis of T cell responses to
      collagen, in cultures of draining lymph node cells, revealed that protection was
      associated with a marked increase in interleukin 4 production concomitant with a
      reduction in interferon gamma levels. Furthermore, in protected mice there was a
      significant reduction in anti-collagen antibody levels as well as an increase in
      the IgG1/IgG2a ratio. These observations show that protection is associated with
      a shift in the Th1/Th2 balance as well as a general reduction in the extent of
      the anti-type II collagen immune response. This suggests that EtxB-receptor
      mediated modulation of lymphocyte responses provides a means of preventing
      autoimmune disease.

PMID- 9144231
TI  - Amyloid-beta peptide-receptor for advanced glycation endproduct interaction
      elicits neuronal expression of macrophage-colony stimulating factor: a
      proinflammatory pathway in Alzheimer disease.
AB  - In Alzheimer disease (AD), neurons are thought to be subjected to the deleterious
      cytotoxic effects of activated microglia. We demonstrate that binding of amyloid
      beta peptide (Abeta) to neuronal Receptor for Advanced Glycation Endproduct
      (RAGE), a cell surface receptor for Abeta, induces macrophage-colony stimulating
      factor (M-CSF) by an oxidant sensitive, nuclear factor kappaB-dependent pathway.
      AD brain shows increased neuronal expression of M-CSF in proximity to Abeta
      deposits, and in cerebrospinal fluid from AD patients there was approximately 5
      fold increased M-CSF antigen (P < 0.01), compared with age-matched controls. M
      CSF released by Abeta-stimulated neurons interacts with its cognate receptor, c
      fms, on microglia, thereby triggering chemotaxis, cell proliferation, increased
      expression of the macrophage scavenger receptor and apolipoprotein E, and
      enhanced survival of microglia exposed to Abeta, consistent with pathologic
      findings in AD. These data delineate an inflammatory pathway triggered by
      engagement of Abeta on neuronal RAGE. We suggest that M-CSF, thus generated,
      contributes to the pathogenesis of AD, and that M-CSF in cerebrospinal fluid
      might provide a means for monitoring neuronal perturbation at an early stage in
      AD.

PMID- 9144232
TI  - Acute leukemia with promyelocytic features in PML/RARalpha transgenic mice.
AB  - Acute promyelocytic leukemia (APL) is associated with reciprocal chromosomal
      translocations involving the retinoic acid receptor alpha (RARalpha) locus on
      chromosome 17. In the majority of cases, RARalpha translocates and fuses with the
      promyelocytic leukemia (PML) gene located on chromosome 15. The resulting fusion
      genes encode the two structurally unique PML/RARalpha and RARalpha/PML fusion
      proteins as well as aberrant PML gene products, the respective pathogenetic roles
      of which have not been elucidated. We have generated transgenic mice in which the
      PML/RARalpha fusion protein is specifically expressed in the myeloid
      promyelocytic lineage. During their first year of life, all the PML/RARalpha
      transgenic mice have an abnormal hematopoiesis that can best be described as a
      myeloproliferative disorder. Between 12 and 14 months of age, 10% of them develop
      a form of acute leukemia with a differentiation block at the promyelocytic stage
      that closely mimics human APL even in its response to retinoic acid. Our results
      are conclusive in vivo evidence that PML/RARalpha plays a crucial role in the
      pathogenesis of APL.

PMID- 9144233
TI  - Differences between males and females in rates of serotonin synthesis in human
      brain.
AB  - Rates of serotonin synthesis were measured in the human brain using positron
      emission tomography. The sensitivity of the method is indicated by the fact that
      measurements are possible even after a substantial lowering of synthesis induced
      by acute tryptophan depletion. Unlike serotonin levels in human brain, which vary
      greatly in different brain areas, rates of synthesis of the indolamine are rather
      uniform throughout the brain. The mean rate of synthesis in normal males was
      found to be 52% higher than in normal females; this marked difference may be a
      factor relevant to the lower incidence of major unipolar depression in males.

PMID- 9144234
TI  - Intracellular misrouting and abnormal secretion of adrenocorticotropin and growth
      hormone in cpefat mice associated with a carboxypeptidase E mutation.
AB  - Cpefat mice carry a mutation in the carboxypeptidase E/H gene which encodes an
      exopeptidase that removes C-terminal basic residues from endoproteolytically
      cleaved hormone intermediates. These mice have endocrine disorders including
      obesity, infertility, and hyperproinsulinemia-diabetes syndrome, but the etiology
      remains an enigma. Because studies have identified membrane carboxypeptidase E as
      a sorting receptor for targeting prohormones to the regulated secretory pathway
      for processing and secretion, the intracellular routing and secretion of pro
      opiomelanocortin/adrenocorticotropin and growth hormone from anterior pituitary
      cells were investigated in Cpefat mice. In Cpefat mice, pro-opiomelanocortin was
      accumulated 24-fold above normal animals in the pituitary and it was poorly
      processed to adrenocorticotropin. Furthermore, pro-opiomelanocortin was secreted
      constitutively at high levels, showing no response to stimulation by
      corticotropin-releasing hormone. Similarly, growth hormone release was
      constitutive and did not respond to high K+ stimulation. Both pro
      opiomelanocortin and growth hormone levels were elevated in the circulation of
      Cpefat mice versus normal mice. These data provide evidence that the lack of
      carboxypeptidase E, the sorting receptor, results in the intracellular misrouting
      and secretion of pro-opiomelanocortin and growth hormone via the constitutive
      pathway in the pituitary of Cpefat mice.

PMID- 9144235
TI  - Purification of primitive human hematopoietic cells capable of repopulating
      immune-deficient mice.
AB  - The purification of primitive human hematopoietic stem cells has been impaired by
      the absence of repopulation assays. By using a stringent two-step strategy
      involving depletion of lineage-positive cells followed by fluorescence-activated
      cell sorting, we have purified a cell population that is highly enriched for
      cells capable of multilineage repopulation in nonobese diabetic/severe combined
      immunodeficient (NOD/SCID) recipients. These SCID-repopulating cells (SRCs) were
      exclusively found in a cell fraction that expressed high levels of CD34 and no
      CD38. Through limiting dilution analysis using Poisson statistics, we calculated
      a frequency of 1 SRC in 617 CD34(+) CD38(-) cells. The highly purified SRC were
      capable of extensive proliferation in NOD/SCID mice. Mice transplanted with 1 SRC
      (at limiting cell doses) were able to produce approximately 400, 000 progeny 6
      weeks after the transplant. Detailed flow cytometric analysis of the marrow of
      highly engrafted mice demonstrated both lymphoid and myeloid differentiation, as
      well as the retention of a significant fraction of CD34(+) CD38(-) cells. These
      highly purified fractions should be useful for identification of the cellular and
      molecular mechanisms that regulate primitive human hematopoietic cells. Moreover,
      the ability to detect and purify primitive cells provides a means to develop
      conditions for maintaining and/or expanding these cells during in vitro culture.

PMID- 9144236
TI  - Induction of maturation of human blood dendritic cell precursors by measles virus
      is associated with immunosuppression.
AB  - As well as inducing a protective immune response against reinfection, acute
      measles is associated with a marked suppression of immune functions against
      superinfecting agents and recall antigens, and this association is the major
      cause of the current high morbidity and mortality rate associated with measles
      virus (MV) infections. Dendritic cells (DCs) are antigen-presenting cells
      crucially involved in the initiation of primary and secondary immune responses,
      so we set out to define the interaction of MV with these cells. We found that
      both mature and precursor human DCs generated from peripheral blood monocytic
      cells express the major MV protein receptor CD46 and are highly susceptible to
      infection with both MV vaccine (ED) and wild-type (WTF) strains, albeit with
      different kinetics. Except for the down-regulation of CD46, the expression
      pattern of functionally important surface antigens on mature DCs was not markedly
      altered after MV infection. However, precursor DCs up-regulated HLA-DR, CD83, and
      CD86 within 24 h of WTF infection and 72 h after ED infection, indicating their
      functional maturation. In addition, interleukin 12 synthesis was markedly
      enhanced after both ED and WTF infection in DCs. On the other hand, MV-infected
      DCs strongly interfered with mitogen-dependent proliferation of freshly isolated
      peripheral blood lymphocytes in vitro. These data indicate that the
      differentiation of effector functions of DCs is not impaired but rather is
      stimulated by MV infection. Yet, mature, activated DCs expressing MV surface
      antigens do give a negative signal to inhibit lymphocyte proliferation and thus
      contribute to MV-induced immunosuppression.

PMID- 9144237
TI  - Selective increase in specific alternative splice variants of tyrosinase in
      murine melanomas: a projected basis for immunotherapy.
AB  - Melanomas tend to become less pigmented in the course of malignant progression.
      Thus, as proliferation increases, the tumors are decreasingly characterized by
      the tissue-specific phenotype of normally differentiated melanocytes. To learn
      whether the decline in melanization is associated with a shift from constitutive
      to alternative splicing of some pigment gene pre-mRNAs, melanomas were collected
      from Tyr-SV40E transgenic mice of the standard C57BL/6 strain. The mRNAs of the
      tyrosinase gene, which has a key role in melanogenesis, were analyzed by
      quantitative reverse transcriptase-PCR in 34 samples from 16 cutaneous tumors and
      9 metastases. The cutaneous tumors included some cases with distinct melanotic
      and amelanotic zones, which were separately analyzed. All tyrosinase transcripts
      found in the melanomas were also found in normal skin melanocytes. However, the
      Delta1b and Delta1d alternatively spliced transcripts, due to deletions within
      the first exon, were specifically augmented in most of the tumors over their very
      low levels in skin; the exceptions were some all-amelanotic tumors in which no
      tyrosinase transcripts were detected. The level of Delta1b rose as high as 11.3%
      of total tyrosinase mRNAs as compared with 0.6% in skin; Delta1d reached 4.0% as
      compared with 0. 8% in skin. Expression of these splice variants was highest in
      the melanotic components of zonal primary tumors, relatively lower in their
      amelanotic components, and still lower in all-amelanotic primary tumors and
      amelanotic metastases. The increase in Delta1b and Delta1d transcripts may be
      predicted to increase the levels of unusual peptides, which could have antigenic
      potential in the tumors, especially in the relatively early phases of malignancy.
      Analyses of the alternative transcripts of other pigment genes may identify
      additional candidate antigens, ultimately enabling melanoma cells in all phases
      of the disease to be represented as a basis for immune intervention.

PMID- 9144239
TI  - Comparison of parametric and nonparametric methods to map oligogenes by linkage.
AB  - A sample of 95 sib pairs affected with insulin-dependent diabetes and typed with
      their normal parents for 28 markers on chromosome 6 has been analyzed by several
      methods. When appropriate parameters are efficiently estimated, a parametric
      model is equivalent to the beta model, which is superior to nonparametric
      alternatives both in single point tests (as found previously) and in multipoint
      tests. Theory is given for meta-analysis combined with allelic association, and
      problems that may be associated with errors of map location and/or marker typing
      are identified. Reducing by multipoint analysis the number of association tests
      in a dense map can give a 3-fold reduction in the critical lod, and therefore in
      the cost of positional cloning.

PMID- 9144238
TI  - The leukocyte response to fluid stress.
AB  - Leukocyte migration from a hemopoietic pool across marrow endothelium requires
      active pseudopod formation and adhesion. Leukocytes rarely show pseudopod
      formation while in circulation. At question then is the mechanism that serves to
      minimize leukocyte pseudopod formation in the circulation. We tested the
      hypothesis that fluid shear stress acts to prevent pseudopod formation. When
      individual human leukocytes (neutrophils, monocytes) spreading on glass surfaces
      in vitro were subjected to fluid shear stress ( approximately 1 dyn/cm2), an
      instantaneous retraction of pseudopods was observed. Removal of the fluid shear
      stress in turn led to the return of pseudopod projection and cell spreading. When
      steady shear stress was prolonged over several minutes, leukocyte swelling occurs
      together with an enhanced random motion of cytoplasmic granules and a reduction
      of cytoplasmic stiffness. The response to shear stress could be suppressed by K+
      channel blockers and chelation of external Ca2+. In rat mesentery microvessels
      after occlusion, circulating leukocytes project pseudopods in free suspension or
      when attached to the endothelium, even though immediately after occlusion only
      few pseudopods were present. When flow was restored, pseudopods on adhering
      leukocytes were retracted and then the cells began to roll and detach from the
      endothelium. In conclusion, plasma shear stress in the circulation serves to
      reduce pseudopod projection and adhesion of circulating leukocytes and vice versa
      reduction of shear stress leads to pseudopod projection and spreading of
      leukocytes on the endothelium.

PMID- 9144240
TI  - Proteolytic processing of the Alzheimer disease-associated presenilin-1 generates
      an in vivo substrate for protein kinase C.
AB  - The majority of familial Alzheimer disease mutations are linked to the recently
      cloned presenilin (PS) genes, which encode two highly homologous proteins (PS-1
      and PS-2). It was shown that the full-length PS-2 protein is phosphorylated
      constitutively within its N-terminal domain by casein kinases, whereas the PS-1
      protein is not. Full-length PS proteins undergo endoproteolytic cleavage within
      their hydrophilic loop domain resulting in the formation of approximately 20-kDa
      C-terminal fragments (CTF) and approximately 30-kDa N-terminal fragments
      [Thinakaran, G., et al. (1996) Neuron 17, 181-190]. Here we describe the
      surprising finding that the CTF of PS-1 is phosphorylated by protein kinase C
      (PKC). Stimulation of PKC causes a 4- to 5-fold increase of the phosphorylation
      of the approximately 20-kDa CTF of PS-1 resulting in reduced mobility in SDS
      gels. PKC-stimulated phosphorylation occurs predominantly on serine residues and
      can be induced either by direct stimulation of PKC with phorbol-12,13-dibutyrate
      or by activation of the m1 acetylcholine receptor-signaling pathway with the
      muscarinic agonist carbachol. However, phosphorylation of full-length PS-1 and PS
      2 is not altered upon PKC stimulation. In addition, a mutant form of PS-1 lacking
      exon 10, which does not undergo endoproteolytic cleavage [Thinakaran, G., et al.
      (1996) Neuron 17, 181-190] is not phosphorylated by PKC, although it still
      contains all PKC phosphorylation sites conserved between different species. These
      results show that PKC phosphorylates the PS-1 CTF. Therefore, endoproteolytic
      cleavage of full-length PS-1 results in the generation of an in vivo substrate
      for PKC. The selective phosphorylation of the PS-1 CTF indicates that the
      physiological and/or pathological properties of the CTF are regulated by PKC
      activity.

PMID- 9144241
TI  - Conservation of the Drosophila lateral inhibition pathway in human lung cancer: a
      hairy-related protein (HES-1) directly represses achaete-scute homolog-1
      expression.
AB  - The achaete-scute genes encode essential transcription factors in normal
      Drosophila and vertebrate nervous system development. Human achaete-scute homolog
      1 (hASH1) is constitutively expressed in a human lung cancer with neuroendocrine
      (NE) features, small cell lung cancer (SCLC), and is essential for development of
      the normal pulmonary NE cells that most resemble this neoplasm. Mechanisms
      regulating achaete-scute homolog expression outside of Drosophila are presently
      unclear, either in the context of the developing nervous system or in normal or
      neoplastic cells with NE features. We now provide evidence that the protein hairy
      enhancer-of-split-1 (HES-1) acts in a similar manner as its Drosophila homolog,
      hairy, to transcriptionally repress achaete-scute expression. HES-1 protein is
      detected at abundant levels in most non-NE human lung cancer cell lines which
      lack hASH1 but is virtually absent in hASH1-expressing lung cancer cells.
      Moreover, induction of HES-1 in a SCLC cell line down-regulates endogenous hASH1
      gene expression. The repressive effect of HES-1 is directly mediated by binding
      of the protein to a class C site in the hASH1 promoter. Thus, a key part of the
      process that determines neural fate in Drosophila is conserved in human lung
      cancer cells. Furthermore, modulation of this pathway may underlie the
      constitutive hASH1 expression seen in NE tumors such as SCLC, the most virulent
      human lung cancer.

PMID- 9144242
TI  - Functional antioxidant responsive elements.
AB  - Exposure of human and rodent cells to a wide variety of chemoprotective compounds
      confers resistance against a broad set of carcinogens. For a subset of the
      chemoprotective compounds, protection is generated by an increase in the
      abundance of protective enzymes like glutathione S-transferases (GST).
      Antioxidant responsive elements (AREs) mediate the transcriptional induction of a
      battery of genes which comprise much of this chemoprotective response system.
      Past studies identified a necessary ARE "core" sequence of RTGACnnnGC, but this
      sequence alone is insufficient to mediate induction. In this study, the
      additional sequences necessary to define a sufficient, functional ARE are
      identified through systematic mutational analysis of the murine GST Ya ARE.
      Introduction of the newly identified necessary nucleotides into the regions
      flanking a nonresponsive, ARE-like, GST-Mu promoter sequence produced an
      inducible element. A screen of the GenBank database with the newly identified ARE
      consensus identified 16 genes which contained the functional ARE consensus
      sequence in their promoters. Included within this group was an ARE sequence from
      the murine ferritin-L promoter that mediated induction when tested. In an
      electrophoretic mobility-shift assay, the ferritin-L ARE was bound by ARE-binding
      protein 1, a protein previously identified as the likely mediator of the
      chemoprotective response. A three-level ARE classification system is presented to
      account for the distinct induction strengths observed in our mutagenesis studies.
      A model of the ARE as a composite regulatory site, where multiple transcription
      factors interact, is presented to account for the complex characteristics of ARE
      mediated chemoprotective gene expression.

PMID- 9144243
TI  - Epigenetic changes at the insulin-like growth factor II/H19 locus in developing
      kidney is an early event in Wilms tumorigenesis.
AB  - Relaxation of imprinting at the insulin-like growth factor II (IFG-II)/H19 locus
      is a major mechanism involved in the onset of sporadic Wilms tumor and several
      other embryonal tumors. The high prevalence of histologically abnormal foci in
      kidney adjacent to Wilms tumors suggests that tumor-predisposing
      genetic/epigenetic lesion might also be found at high frequency in Wilms tumor
      bearing kidneys. Focusing on Wilms tumors with relaxation of IFG-II imprinting,
      we determined the frequency of epigenetic change at the IFG-II/H19 locus in
      adjacent kidney. In all kidneys adjacent to these Wilms tumors, we detected
      substantial mosaicism for a population of cells with relaxation of IFG-II
      imprinting and biallelic H19 methylation, regardless of whether the patient had a
      tumor-predisposing syndrome or not. The high proportion of epigenetically
      modified cells among "normal" tissue indicates that the epigenetic error occurred
      very early in development, before the onset of Wilms tumor. Not only does this
      suggest that the major Wilms tumor-predisposing event occurs within the first few
      days of development, but it also suggests that sporadic Wilms tumor may represent
      one end of a spectrum of overgrowth disorders characterized by mosaic epigenetic
      change at the IFG-II/H19 locus.

PMID- 9144244
TI  - Thioredoxin-linked mitigation of allergic responses to wheat.
AB  - Thioredoxin, a ubiquitous 12-kDa regulatory disulfide protein, was found to
      reduce disulfide bonds of allergens (convert S-S to 2 SH) and thereby mitigate
      the allergenicity of commercial wheat preparations. Allergenic strength was
      determined by skin tests with a canine model for food allergy. Statistically
      significant mitigation was observed with 15 of 16 wheat-sensitive animals. The
      allergenicity of the protein fractions extracted from wheat flour with the
      indicated solvent was also assessed: the gliadins (ethanol) were the strongest
      allergens, followed by glutenins (acetic acid), albumins (water), and globulins
      (salt water). Of the gliadins, the alpha and beta fractions were most potent,
      followed by the gamma and omega types. Thioredoxin mitigated the allergenicity
      associated with the major protein fractions-i.e, the gliadins (including the
      alpha, beta, and gamma types) and the glutenins-but gave less consistent results
      with the minor fractions, the albumins and globulins. In all cases, mitigation
      was specific to thioredoxin that had been reduced either enzymically by NADPH and
      NADP-thioredoxin reductase or chemically by dithiothreitol; reduced glutathione
      was without significant effect. As in previous studies, thioredoxin was
      particularly effective in the reduction of intramolecular (intrachain) disulfide
      bonds. The present results demonstrate that the reduction of these disulfide
      bonds is accompanied by a statistically significant decrease in allergenicity of
      the active proteins. This decrease occurs alongside the changes identified
      previously-i.e., increased susceptibility to proteolysis and heat, and altered
      biochemical activity. The findings open the door to the testing of the
      thioredoxin system in the production of hypoallergenic, more-digestible foods.

PMID- 9144245
TI  - Experimental surgery to create subgenomes of Bacillus subtilis 168.
AB  - The 4,188-kb circular genome of Bacillus subtilis 168 was artificially dissected
      into two stable circular chromosomes in vivo, one being the 3,878-kb main genome
      and the other the 310-kb subgenome that was recovered as covalently closed
      circular DNA in CsCl-ethidium bromide ultracentrifugation. The minimal
      requirements to physically separate the 310-kb DNA segment out of the genome were
      two interrepeat homologous sequences and an origin of DNA replication between
      them. The subgenome originated from the 1,255-1, 551-kb region of the B. subtilis
      genome was essential for the cell to survive because the subgenome was not lost
      from the cell. The finding that the B. subtilis genome has a potential to be
      divided and the resulting two replicons stably maintained may shed light on
      origins and formation mechanisms of giant plasmids or second chromosomes present
      in many bacteria. Similar excision or its reversal process, i.e., integration of
      large sized covalently closed circular DNA pieces into the main genome, implies
      significant roles of subgenomes in the exchange of genetic information and size
      variation of bacterial genomes in bacterial evolution.

PMID- 9144246
TI  - Chaperonin filaments: the archaeal cytoskeleton?
AB  - Chaperonins are high molecular mass double-ring structures composed of 60-kDa
      protein subunits. In the hyperthermophilic archaeon Sulfolobus shibatae the two
      chaperonin proteins represent approximately 4% of its total protein and have a
      combined intracellular concentration of >30 mg/ml. At concentrations >/= 0.5
      mg/ml purified chaperonins form filaments in the presence of Mg2+ and
      nucleotides. Filament formation requires nucleotide binding (not hydrolysis), and
      occurs at physiological temperatures in biologically relevant buffers, including
      a buffer made from cell extracts. These observations suggest that chaperonin
      filaments may exist in vivo and the estimated 4600 chaperonins per cell suggest
      that such filaments could form an extensive cytostructure. We observed
      filamentous structures in unfixed, uranyl-acetate-stained S. shibatae cells,
      which resemble the chaperonin filaments in size and appearance. ImmunoGold
      (Janssen) labeling using chaperonin antibodies indicated that many chaperonins
      are associated with insoluble cellular structures and these structures appear to
      be filamentous in some areas, although they could not be uranyl-acetate-stained.
      The existence of chaperonin filaments in vivo suggests a mechanism whereby their
      protein-folding activities can be regulated. More generally, the filaments
      themselves may play a cytoskeletal role in Archaea.

PMID- 9144247
TI  - Rotavirus contains integrin ligand sequences and a disintegrin-like domain that
      are implicated in virus entry into cells.
AB  - Rotavirus contains two outer capsid viral proteins, the spike protein VP4 and
      major capsid component VP7, both of which are implicated in cell entry. We show
      that VP4 and VP7 contain tripeptide sequences previously shown to act as
      recognition sites for integrins in extracellular matrix proteins. VP4 contains
      the alpha2beta1 integrin ligand site DGE. In VP7, the alphaxbeta2 integrin ligand
      site GPR and the alpha4beta1 integrin ligand site LDV are embedded in a novel
      disintegrin-like domain that also shows sequence similarity to fibronectin and
      the tie receptor tyrosine kinase. Microorganism sequence homology to these ligand
      motifs and to disintegrins has not been reported previously. In our experiments,
      peptides including these rotaviral tripeptides and mAbs directed to these
      integrins specifically blocked rotavirus infection of cells shown to express
      alpha2beta1 and beta2 integrins. Rotavirus VP4-mediated cell entry may involve
      the alpha2beta1 integrin, whereas VP7 appears to interact with alphaxbeta2 and
      alpha4beta1 integrins.

PMID- 9144249
TI  - Abnormal dendritic spines in fragile X knockout mice: maturation and pruning
      deficits.
AB  - Fragile X syndrome arises from blocked expression of the fragile X mental
      retardation protein (FMRP). Golgi-impregnated mature cerebral cortex from fragile
      X patients exhibits long, thin, tortuous postsynaptic spines resembling spines
      observed during normal early neocortical development. Here we describe dendritic
      spines in Golgi-impregnated cerebral cortex of transgenic fragile X gene (Fmr1)
      knockout mice that lack expression of the protein. Dendritic spines on apical
      dendrites of layer V pyramidal cells in occipital cortex of fragile X knockout
      mice were longer than those in wild-type mice and were often thin and tortuous,
      paralleling the human syndrome and suggesting that FMRP expression is required
      for normal spine morphological development. Moreover, spine density along the
      apical dendrite was greater in the knockout mice, which may reflect impaired
      developmental organizational processes of synapse stabilization and elimination
      or pruning.

PMID- 9144248
TI  - Fragile X mental retardation protein is translated near synapses in response to
      neurotransmitter activation.
AB  - Local translation of proteins in distal dendrites is thought to support synaptic
      structural plasticity. We have previously shown that metabotropic glutamate
      receptor (mGluR1) stimulation initiates a phosphorylation cascade, triggering
      rapid association of some mRNAs with translation machinery near synapses, and
      leading to protein synthesis. To determine the identity of these mRNAs, a cDNA
      library produced from distal nerve processes was used to screen synaptic
      polyribosome-associated mRNA. We identified mRNA for the fragile X mental
      retardation protein (FMRP) in these processes by use of synaptic subcellular
      fractions, termed synaptoneurosomes. We found that this mRNA associates with
      translational complexes in synaptoneurosomes within 1-2 min after mGluR1
      stimulation of this preparation, and we observed increased expression of FMRP
      after mGluR1 stimulation. In addition, we found that FMRP is associated with
      polyribosomal complexes in these fractions. In vivo, we observed FMRP
      immunoreactivity in spines, dendrites, and somata of the developing rat brain,
      but not in nuclei or axons. We suggest that rapid production of FMRP near
      synapses in response to activation may be important for normal maturation of
      synaptic connections.

PMID- 9144250
TI  - Interaction of the synprint site of N-type Ca2+ channels with the C2B domain of
      synaptotagmin I.
AB  - N-type Ca2+ channels mediate Ca2+ influx, which initiates fast exocytosis of
      neurotransmitters at synapses, and they interact directly with the SNARE proteins
      syntaxin and SNAP-25 (synaptosome-associated protein of 25 kDa) through a
      synaptic protein interaction (synprint) site in the intracellular loop connecting
      domains II and III of their alpha1B subunits. Introduction of peptides containing
      the synprint site into presynaptic neurons reversibly inhibits synaptic
      transmission, confirming the importance of interactions with this site in
      synaptic transmission. Here we report a direct interaction of the synprint
      peptide from N-type Ca2+ channels with synaptotagmin I, an important Ca2+ sensor
      for exocytosis, as measured by an affinity-chromatography binding assay and a
      solid-phase immunoassay. This interaction is mediated by the second C2 domain
      (C2B) of synaptotagmin I, but is not regulated by Ca2+. Using both immobilized
      recombinant proteins and native presynaptic membrane proteins, we found that the
      synprint peptide and synaptotagmin competitively interact with syntaxin. This
      interaction is Ca2+-dependent because of the Ca2+ dependence of the interactions
      between syntaxin and these two proteins. These results provide a molecular basis
      for a physical link between Ca2+ channels and synaptotagmin, and suggest that N
      type Ca2+ channels may undergo a complex series of Ca2+-dependent interactions
      with multiple presynaptic proteins during neurotransmission.

PMID- 9144251
TI  - The structure and precision of retinal spike trains.
AB  - Assessing the reliability of neuronal spike trains is fundamental to an
      understanding of the neural code. We measured the reproducibility of retinal
      responses to repeated visual stimuli. In both tiger salamander and rabbit, the
      retinal ganglion cells responded to random flicker with discrete, brief periods
      of firing. For any given cell, these firing events covered only a small fraction
      of the total stimulus time, often less than 5%. Firing events were very
      reproducible from trial to trial: the timing jitter of individual spikes was as
      low as 1 msec, and the standard deviation in spike count was often less than 0.5
      spikes. Comparing the precision of spike timing to that of the spike count showed
      that the timing of a firing event conveyed several times more visual information
      than its spike count. This sparseness and precision were general characteristics
      of ganglion cell responses, maintained over the broad ensemble of stimulus
      waveforms produced by random flicker, and over a range of contrasts. Thus, the
      responses of retinal ganglion cells are not properly described by a firing
      probability that varies continuously with the stimulus. Instead, these neurons
      elicit discrete firing events that may be the fundamental coding symbols in
      retinal spike trains.

PMID- 9144252
TI  - Novel form of crosstalk between G protein and tyrosine kinase pathways.
AB  - Neuronal Ca2+ channels are inhibited by a variety of transmitter receptors
      coupled to Go-type GTP-binding proteins. Go has been postulated to work via a
      direct interaction between an activated G protein subunit and the Ca2+ channel
      complex. Here we show that the inhibition of sensory neuron N-type Ca2+ channels
      produced by gamma-aminobutyric acid involves a novel, rapidly activating tyrosine
      kinase signaling pathway that is mediated by Galphao and a src-like kinase. In
      contrast to other recently described G protein-coupled tyrosine kinase pathways,
      the Galphao-mediated modulation requires neither protein kinase C nor
      intracellular Ca2+. The results suggest that this pathway mediates rapid receptor
      G protein signaling in the nervous system and support the existence of a
      previously unrecognized form of crosstalk between G protein and tyrosine kinase
      pathways.

PMID- 9144253
TI  - Stimulation of amyloid precursor protein synthesis by adrenergic receptors
      coupled to cAMP formation.
AB  - Amyloid plaques in Alzheimer disease are primarily aggregates of Abeta peptides
      that are derived from the amyloid precursor protein (APP). Neurotransmitter
      agonists that activate phosphatidylinositol hydrolysis and protein kinase C
      stimulate APP processing and generate soluble, non-amyloidogenic APP (APPs).
      Elevations in cAMP oppose this stimulatory effect and lead to the accumulation of
      cell-associated APP holoprotein containing amyloidogenic Abeta peptides. We now
      report that cAMP signaling can also increase cellular levels of APP holoprotein
      by stimulating APP gene expression in astrocytes. Treatment of astrocytes with
      norepinephrine or isoproterenol for 24 h increased both APP mRNA and holoprotein
      levels, and these increases were blocked by the beta-adrenergic antagonist
      propranolol. Treatment with 8-bromo-adenosine 3',5'-cyclic monophosphate or
      forskolin for 24 h similarly increased APP holoprotein levels; astrocytes were
      also transformed into process-bearing cells expressing increased amounts of glial
      fibrillary acidic protein, suggesting that these cells resemble reactive
      astrocytes. The increases in APP mRNA and holoprotein in astrocytes caused by
      cAMP stimulation were inhibited by the immunosuppressant cyclosporin A. Our study
      suggests that APP overexpression by reactive astrocytes during neuronal injury
      may contribute to Alzheimer disease neuropathology, and that immunosuppressants
      can inhibit cAMP activation of APP gene transcription.

PMID- 9144254
TI  - Voltage-controlled gating in a large conductance Ca2+-sensitive K+channel (hslo).
AB  - Large conductance calcium- and voltage-sensitive K+ (MaxiK) channels share
      properties of voltage- and ligand-gated ion channels. In voltage-gated channels,
      membrane depolarization promotes the displacement of charged residues contained
      in the voltage sensor (S4 region) inducing gating currents and pore opening. In
      MaxiK channels, both voltage and micromolar internal Ca2+ favor pore opening. We
      demonstrate the presence of voltage sensor rearrangements with voltage (gating
      currents) whose movement and associated pore opening is triggered by voltage and
      facilitated by micromolar internal Ca2+ concentration. In contrast to other
      voltage-gated channels, in MaxiK channels there is charge movement at potentials
      where the pore is open and the total charge per channel is 4-5 elementary
      charges.

PMID- 9144255
TI  - Peptidyl prolyl cis-trans isomerase activity of cyclophilin A in functional homo
      oligomeric receptor expression.
AB  - The functional expression of homo-oligomeric alpha7 neuronal nicotinic and type 3
      serotonin receptors is dependent on the activity of a cyclophilin. In this paper
      we demonstrate that the mechanism of cyclophilin action during functional homo
      oligomeric receptor expression in Xenopus oocytes is distinct from the
      calcineurin-dependent immunosuppressive mechanism by showing that a
      nonimmunosuppressive analog of cyclosporin A (CsA), SDZ 211-811, reduces
      functional receptor expression to the same extent as CsA. The cytoplasmic subtype
      of cyclophilin, cyclophilin A (CyPA), appears to be required for functional
      receptor expression. This is because overexpression of CyPA and a CyPA mutant
      that is deficient in CsA binding activity reverses CsA-induced reduction in
      functional receptor expression. The mechanism of action of CyPA is likely to
      involve its prolyl isomerase activity because a mutant CyPA with a single amino
      acid substitution (arginine 55 to alanine) that is predicted to produce a 1000
      fold attenuation in isomerase activity fails to reverse the cyclosporin A effect.
      Our data also suggest that CyPA does not form a stable complex with receptor
      subunits.

PMID- 9144256
TI  - Neural mechanisms underlying binocular fusion and stereopsis: position vs. phase.
AB  - The visual system utilizes binocular disparity to discriminate the relative depth
      of objects in space. Since the striate cortex is the first site along the central
      visual pathways at which signals from the left and right eyes converge onto a
      single neuron, encoding of binocular disparity is thought to begin in this
      region. There are two possible mechanisms for encoding binocular disparity
      through simple cells in the striate cortex: a difference in receptive field (RF)
      position between the two eyes (RF position disparity) and a difference in RF
      profile between the two eyes (RF phase disparity). Although there have been
      studies supporting each of the two encoding mechanisms, both mechanisms have not
      been examined in a single study. Therefore, the relative roles of the two
      mechanisms have not been determined. To address this issue, we have mapped left
      and right eye RFs of simple cells in the cat's striate cortex using binary m
      sequence noise, and then we have estimated RF position and phase disparities. We
      find that RF position disparities are generally limited to small values that are
      not sufficient to encode large binocular disparities. In contrast, RF phase
      disparities cover a wide range of binocular disparities and exhibit dependencies
      on orientation and spatial frequency in a manner expected for a mechanism that
      encodes binocular disparity. These results indicate that binocular disparity is
      mainly encoded through RF phase disparity. However, RF position disparity may
      play a significant role for cells with high spatial frequency selectivity, which
      are constrained to small RF phase disparities.

PMID- 9144257
TI  - Slow skeletal troponin I gene transfer, expression, and myofilament incorporation
      enhances adult cardiac myocyte contractile function.
AB  - The functional significance of the developmental transition from slow skeletal
      troponin I (ssTnI) to cardiac TnI (cTnI) isoform expression in cardiac myocytes
      remains unclear. We show here the effects of adenovirus-mediated ssTnI gene
      transfer on myofilament structure and function in adult cardiac myocytes in
      primary culture. Gene transfer resulted in the rapid, uniform, and nearly
      complete replacement of endogenous cTnI with the ssTnI isoform with no detected
      changes in sarcomeric ultrastructure, or in the isoforms and stoichiometry of
      other myofilament proteins compared with control myocytes over 7 days in primary
      culture. In functional studies on permeabilized single cardiac myocytes, the
      threshold for Ca2+-activated contraction was significantly lowered in adult
      cardiac myocytes expressing ssTnI relative to control values. The tension-Ca2+
      relationship was unchanged from controls in primary cultures of cardiac myocytes
      treated with adenovirus containing the adult cardiac troponin T (TnT) or cTnI
      cDNAs. These results indicate that changes in Ca2+ activation of tension in ssTnI
      expressing cardiac myocytes were isoform-specific, and not due to nonspecific
      functional changes resulting from overexpression of a myofilament protein.
      Further, Ca2+-activated tension development was enhanced in cardiac myocytes
      expressing ssTnI compared with control values under conditions mimicking the
      acidosis found during myocardial ischemia. These results show that ssTnI enhances
      contractile sensitivity to Ca2+ activation under physiological and acidic pH
      conditions in adult rat cardiac myocytes, and demonstrate the utility of
      adenovirus vectors for rapid and efficient genetic modification of the cardiac
      myofilament for structure/function studies in cardiac myocytes.

PMID- 9144258
TI  - Congestive heart failure in rats is associated with increased expression and
      targeting of aquaporin-2 water channel in collecting duct.
AB  - We tested whether severe congestive heart failure (CHF), a condition associated
      with excess free-water retention, is accompanied by altered regulation of the
      vasopressin-regulated water channel, aquaporin-2 (AQP2), in the renal collecting
      duct. CHF was induced by left coronary artery ligation. Compared with sham
      operated animals, rats with CHF had severe heart failure with elevated left
      ventricular end-diastolic pressures (LVEDP): 26.9 +/- 3.4 vs. 4.1 +/- 0.3 mmHg,
      and reduced plasma sodium concentrations (142.2 +/- 1. 6 vs. 149.1 +/- 1.1
      mEq/liter). Quantitative immunoblotting of total kidney membrane fractions
      revealed a significant increase in AQP2 expression in animals with CHF (267 +/-
      53%, n = 12) relative to sham-operated controls (100 +/- 13%, n = 14). In
      contrast, immunoblotting demonstrated a lack of an increase in expression of AQP1
      and AQP3 water channel expression, indicating that the effect on AQP2 was
      selective. Furthermore, postinfarction animals without LVEDP elevation or plasma
      Na reduction showed no increase in AQP2 expression (121 +/- 28% of sham levels, n
      = 6). Immunocytochemistry and immunoelectron microscopy demonstrated very
      abundant labeling of the apical plasma membrane and relatively little labeling of
      intracellular vesicles in collecting duct cells from rats with severe CHF,
      consistent with enhanced trafficking of AQP2 to the apical plasma membrane. The
      selective increase in AQP2 expression and enhanced plasma membrane targeting
      provide an explanation for the development of water retention and hyponatremia in
      severe CHF.

PMID- 9144259
TI  - Scanning mutagenesis of the putative transmembrane segments of Kir2.1, an inward
      rectifier potassium channel.
AB  - Structural models of inward rectifier K+ channels incorporate four identical or
      homologous subunits, each of which has two hydrophobic segments (M1 and M2) which
      are predicted to span the membrane as alpha helices. Since hydrophobic
      interactions between proteins and membrane lipids are thought to be generally of
      a nonspecific nature, we attempted to identify lipid-contacting residues in
      Kir2.1 as those which tolerate mutation to tryptophan, which has a large
      hydrophobic side chain. Tolerated mutations were defined as those which produced
      measurable inwardly rectifying currents in Xenopus oocytes. To distinguish
      between water-accessible positions and positions adjacent to membrane lipids or
      within the protein interior we also mutated residues in M1 and M2 individually to
      aspartate, since an amino acid with a charged side chain should not be tolerated
      at lipid-facing or interior positions, due to the energy cost of burying a charge
      in a hydrophobic environment. Surprisingly, 17 out of 20 and 17 out of 22 non
      tryptophan residues in M1 and M2, respectively, tolerated being mutated to
      tryptophan. Moreover, aspartate was tolerated at 15 out of 22 and 15 out of 21
      non-aspartate M1 and M2 positions respectively. Periodicity in the pattern of
      tolerated vs. nontolerated mutations consistent with alpha helices or beta
      strands did not emerge convincingly from these data. We consider the possibility
      that parts of M1 and M2 may be in contact with water.

PMID- 9144260
TI  - A novel multifunctional O-methyltransferase implicated in a dual methylation
      pathway associated with lignin biosynthesis in loblolly pine.
AB  - S-adenosyl-L-methionine (SAM)-dependent O-methyltransferases (OMTs) catalyze the
      methylation of hydroxycinnamic acid derivatives for the synthesis of methylated
      plant polyphenolics, including lignin. The distinction in the extent of
      methylation of lignins in angiosperms and gymnosperms, mediated by substrate
      specific OMTs, represents one of the fundamental differences in lignin
      biosynthesis between these two classes of plants. In angiosperms, two types of
      structurally and functionally distinct lignin pathway OMTs, caffeic acid 3-O
      methyltransferases (CAOMTs) and caffeoyl CoA 3-O-methyltransferases (CCoAOMTs),
      have been reported and extensively studied. However, little is known about lignin
      pathway OMTs in gymnosperms. We report here the first cloning of a loblolly pine
      (Pinus taeda) xylem cDNA encoding a multifunctional enzyme, SAM:hydroxycinnamic
      Acids/hydroxycinnamoyl CoA Esters OMT (AEOMT). The deduced protein sequence of
      AEOMT is partially similar to, but clearly distinguishable from, that of CAOMTs
      and does not exhibit any significant similarity with CCoAOMT protein sequences.
      However, functionally, yeast-expressed AEOMT enzyme catalyzed the methylation of
      CAOMT substrates, caffeic and 5-hydroxyferulic acids, as well as CCoAOMT
      substrates, caffeoyl CoA and 5-hydroxyferuloyl CoA esters, with similar specific
      activities and was completely inactive with substrates associated with flavonoid
      synthesis. The lignin-related substrates were also efficiently methylated in
      crude extracts of loblolly pine secondary xylem. Our results support the notion
      that, in the context of amino acid sequence and biochemical function, AEOMT
      represents a novel SAM-dependent OMT, with both CAOMT and CCoAOMT activities and
      thus the potential to mediate a dual methylation pathway in lignin biosynthesis
      in loblolly pine xylem.

PMID- 9144263
TI  - Concordance of gene genealogies reveals reproductive isolation in the pathogenic
      fungus Coccidioides immitis.
AB  - Simple cladogenetic theory suggests that gene genealogies can be used to detect
      mixis in a population and delineate reproductively isolated groups within sexual
      taxa. We have taken this approach in a study of Coccidioides immitis, an
      ascomycete fungus responsible for a recent epidemic of coccidioidomycosis (Valley
      fever) in California. To test whether this fungus represents a single sexual
      species throughout its entire geographic range, we have compared genealogies from
      fragments of five nuclear genes. The five genealogies show multiple
      incompatibilities indicative of sex, but also share a branch that partitions the
      isolates into two reproductively isolated taxa, one centered in California and
      the other outside California. We conclude that coccidioidomycosis can be caused
      by two distinct noninterbreeding taxa. This result should aid the future study of
      the disease and illustrates the utility of the genealogical approach in
      population genetics.

PMID- 9144264
TI  - Rhizobium gone native: unexpected plasmid stability of indigenous Rhizobium
      leguminosarum.
AB  - Lateral transfer of bacterial plasmids is thought to play an important role in
      microbial evolution and population dynamics. However, this assumption is based
      primarily on investigations of medically or agriculturally important bacterial
      species. To explore the role of lateral transfer in the evolution of bacterial
      systems not under intensive, human-mediated selection, we examined the
      association of genotypes at plasmid-encoded and chromosomal loci of native
      Rhizobium, the nitrogen-fixing symbiont of legumes. To this end, Rhizobium
      leguminosarum strains nodulating sympatric species of native Trifolium were
      characterized genetically at plasmid-encoded symbiotic (sym) regions (nodulation
      AB and nodulation CIJT loci) and a repeated chromosomal locus not involved in the
      symbiosis with legumes. Restriction fragment length polymorphism analysis was
      used to distinguish genetic groups at plasmid and chromosomal loci. The
      correlation between major sym and chromosomal genotypes and the distribution of
      genotypes across host plant species and sampling location were determined using
      chi2 analysis. In contrast to findings of previous studies, a strict association
      existed between major sym plasmid and chromosomal genetic groups, suggesting a
      lack of successful sym plasmid transfer between major Rhizobium chromosomal
      types. These data indicate that previous observations of sym plasmid transfer in
      agricultural settings may seriously overestimate the rates of successful
      conjugation in systems not impacted by human activities. In addition, a nonrandom
      distribution of Rhizobium genotypes across host plant species and sampling site
      demonstrates the importance of both factors in shaping Rhizobium population
      dynamics.

PMID- 9144265
TI  - Cultural universals: measuring the semantic structure of emotion terms in English
      and Japanese.
AB  - Research is presented on the semantic structure of 15 emotion terms as measured
      by judged-similarity tasks for monolingual English-speaking and monolingual and
      bilingual Japanese subjects. A major question is the relative explanatory power
      of a single shared model for English and Japanese versus culture-specific models
      for each language. The data support a shared model for the semantic structure of
      emotion terms even though some robust and significant differences are found
      between English and Japanese structures. The Japanese bilingual subjects use a
      model more like English when performing tasks in English than when performing the
      same task in Japanese.

PMID- 9144266
TI  - Quantification of maximum-entropy spectrum reconstructions.
AB  - Maximum-entropy spectrum reconstruction derives much of its power from its
      nonlinearity. This nonlinearity causes difficulties in several contexts, however,
      including computation of multidimensional spectra and quantification of
      reconstructed spectra. We describe two methods for avoiding these difficulties: a
      "Constant-lambda" algorithm for performing row-wise reconstructions, which uses a
      fixed weighting of the entropy and the experimental constraint in the objective
      function, and in situ error analysis, for calibrating the nonlinearity. These
      methods are applied to data from quantitative J-correlation and relaxation
      experiments.

PMID- 9144267
TI  - RF gradient BIRD/TANGO sequence to eliminate uncoupled magnetization.
AB  - A modification of the BIRD and TANGO sequences is presented which employs
      radiofrequency field gradients to eliminate the net magnetization from uncoupled
      spins, while completely preserving coupled magnetization. The standard BIRD and
      TANGO sequences cause selective nutation of protons directly bound to a coupling
      partner, while returning uncoupled magnetization to +z. These sequences lend
      themselves naturally to modification using RF gradients, which require no
      increase in pulse-sequence complexity while providing substantial suppression of
      uncoupled resonances and elimination of typical antiphase and multiple-quantum
      error terms that arise from improperly set pulse lengths or delays. In the RF
      gradient BIRD/TANGO sequence, the uncoupled magnetization is dephased in a plane
      orthogonal to the RF axis, while the desired signal components are refocused,
      effectively in a rotary echo. The sequence has applications to solvent
      suppression and selective isotopomer excitation. It is demonstrated for selective
      excitation of the satellites in a sample of chloroform, yielding suppression of
      the uncoupled magnetization by factor of approximately 800.

PMID- 9144268
TI  - Germany gets warning on access to sequence data.

PMID- 9144269
TI  - Ruttgers and Chirac seek cloning ban.

PMID- 9144270
TI  - Mining waste poisons river basin.

PMID- 9144271
TI  - The dog did nothing in the night-time.

PMID- 9144272
TI  - The dog did nothing in the night-time.

PMID- 9144273
TI  - Cloning humans.

PMID- 9144274
TI  - Cloning humans.

PMID- 9144275
TI  - Down or out in blood and lymph?

PMID- 9144276
TI  - Palaeoanthropology. They might be giants.

PMID- 9144277
TI  - Language impairment. Listening out for subtle deficits.

PMID- 9144278
TI  - Protein transport. A fusion of new ideas.

PMID- 9144279
TI  - Evolutionary genetics. The muddle about mutations.

PMID- 9144280
TI  - Neutrality or selection?

PMID- 9144282
TI  - How good a model is the Fugu genome?

PMID- 9144281
TI  - DNA answers the call of pipistrelle bat species.

PMID- 9144283
TI  - How good a model is the Fugu genome?

PMID- 9144284
TI  - Altered cell differentiation and proliferation in mice lacking p57KIP2 indicates
      a role in Beckwith-Wiedemann syndrome.
AB  - Mice lacking the imprinted Cdk inhibitor p57(KIP2) have altered cell
      proliferation and differentiation, leading to abdominal muscle defects; cleft
      palate; endochondral bone ossification defects with incomplete differentiation of
      hypertrophic chondrocytes; renal medullary dysplasia; adrenal cortical
      hyperplasia and cytomegaly; and lens cell hyperproliferation and apoptosis. Many
      of these phenotypes are also seen in patients with Beckwith-Wiedemann syndrome, a
      pleiotropic hereditary disorder characterized by overgrowth and predisposition to
      cancer, suggesting that loss of p57(KIP2) expression may play a role in the
      condition.

PMID- 9144285
TI  - Total synthesis of the potential anticancer vaccine KH-1 adenocarcinoma antigen.
AB  - Human tumours are often marked by the expression of unusual carbohydrate
      structural motifs. These carbohydrate domains are manifested as cell-surface
      bound glycolipids or glycoproteins. This raises the possibility of using cell
      free equivalents of these domain compounds, obtained by total synthesis with a
      view towards triggering some level of immune response. In fact, the serum of mice
      immunized with fully synthetic compounds that mimic cell-surface tumour antigens
      has already been shown to recognize pertinent human cancer cell lines. Further
      advances in this field depend critically on the availability of these tumour
      associated carbohydrate antigens which cannot be readily isolated from natural
      sources in sufficient quantities. Here we present the successful total synthesis
      of an adenocarcinoma antigen, KH-1, and of a bioconjugatable analogue which can
      bind to a carrier protein. These results illustrate the capabilities of
      oligosaccharide synthesis for reconstructing the challenging structural motifs
      characteristic of carbohydrate antigens, and thereby open up new possibilities
      for the development of anticancer vaccines.

PMID- 9144286
TI  - Body mass and encephalization in Pleistocene Homo.
AB  - Many dramatic changes in morphology within the genus Homo have occurred over the
      past 2 million years or more, including large increases in absolute brain size
      and decreases in postcanine dental size and skeletal robusticity. Body mass, as
      the 'size' variable against which other morphological features are usually
      judged, has been important for assessing these changes. Yet past body mass
      estimates for Pleistocene Homo have varied greatly, sometimes by as much as 50%
      for the same individuals. Here we show that two independent methods of body-mass
      estimation yield concordant results when applied to Pleistocene Homo specimens.
      On the basis of an analysis of 163 individuals, body mass in Pleistocene Homo
      averaged significantly (about 10%) larger than a representative sample of living
      humans. Relative to body mass, brain mass in late archaic H. sapiens
      (Neanderthals) was slightly smaller than in early 'anatomically modern' humans,
      but the major increase in encephalization within Homo occurred earlier during the
      Middle Pleistocene (600-150 thousand years before present (kyr BP)), preceded by
      a long period of stasis extending through the Early Pleistocene (1,800 kyr BP).

PMID- 9144287
TI  - Deficits in auditory temporal and spectral resolution in language-impaired
      children.
AB  - Between 3 and 6 per cent of children who are otherwise unimpaired have extreme
      difficulties producing and understanding spoken language. This disorder is
      typically labelled specific language impairment. Children diagnosed with specific
      language impairment often have accompanying reading difficulties (dyslexia), but
      not all children with reading difficulties have specific language impairment.
      Some researchers claim that language impairment arises from failures specific to
      language or cognitive processing. Others hold that language impairment results
      from a more elemental problem that makes affected children unable to hear the
      acoustic distinctions among successive brief sounds in speech. Here we report the
      results of psychophysical tests employing simple tones and noises showing that
      children with specific language impairment have severe auditory perceptual
      deficits for brief but not long tones in particular sound contexts. Our data
      support the view that language difficulties result from problems in auditory
      perception, and provide further information about the nature of these perceptual
      problems that should contribute to improving the diagnosis and treatment of
      language impairment and related disorders.

PMID- 9144288
TI  - Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the
      sulphonylurea receptor.
AB  - ATP-sensitive potassium channels (K-ATP channels) couple cell metabolism to
      electrical activity and are important in the physiology and pathophysiology of
      many tissues. In pancreatic beta-cells, K-ATP channels link changes in blood
      glucose concentration to insulin secretion. They are also the target for
      clinically important drugs such as sulphonylureas, which stimulate secretion, and
      the K+ channel opener diazoxide, which inhibits insulin release. Metabolic
      regulation of K-ATP channels is mediated by changes in intracellular ATP and Mg
      ADP levels, which inhibit and activate the channel, respectively. The beta-cell K
      ATP channel is a complex of two proteins: an inward-rectifier K+ channel subunit,
      Kir6.2, and the sulphonylurea receptor, SUR1. We show here that the primary site
      at which ATP acts to mediate K-ATP channel inhibition is located on Kir6.2, and
      that SUR1 is required for sensitivity to sulphonylureas and diazoxide and for
      activation by Mg-ADP.

PMID- 9144289
TI  - Quantification of latent tissue reservoirs and total body viral load in HIV-1
      infection.
AB  - The capacity of HIV-1 to establish latent infection of CD4+ T cells may allow
      viral persistence despite immune responses and antiretroviral therapy.
      Measurements of infectious virus and viral RNA in plasma and of infectious virus,
      viral DNA and viral messenger RNA species in infected cells all suggest that HIV
      1 replication continues throughout the course of infection. Uncertainty remains
      over what fraction of CD4+ T cells are infected and whether there are latent
      reservoirs for the virus. We show here that during the asymptomatic phase of
      infection there is an extremely low total body load of latently infected resting
      CD4+ T cells with replication-competent integrated provirus (<10(7) cells). The
      most prevalent form of HIV-1 DNA in resting and activated CD4+ T cells is a full
      length, linear, unintegrated form that is not replication competent. The
      infection progresses even though at any given time in the lymphoid tissues
      integrated HIV-1 DNA is present in only a minute fraction of the susceptible
      populations, including resting and activated CD4+ T cells and macrophages.

PMID- 9144290
TI  - Decay characteristics of HIV-1-infected compartments during combination therapy.
AB  - Analysis of changes in viral load after initiation of treatment with potent
      antiretroviral agents has provided substantial insight into the dynamics of human
      immunodeficiency virus type 1 (HIV-1). The concentration of HIV-1 in plasma drops
      by approximately 99% in the first two weeks of treatment owing to the rapid
      elimination of free virus with a half-life (t1/2) of < or =6 hours and loss of
      productively infected cells with a t1/2 of 1.6 days. Here we show that with
      combination therapy this initial decrease is followed by a slower second-phase
      decay of plasma viraemia. Detailed mathematical analysis shows that the loss of
      long-lived infected cells (t1/2 of 1-4 weeks) is a major contributor to the
      second phase, whereas the activation of latently infected lymphocytes (t1/2 of
      0.5-2 weeks) is only a minor source. Based on these decay characteristics, we
      estimate that 2.3-3.1 years of a completely inhibitory treatment would be
      required to eliminate HIV-1 from these compartments. To eradicate HIV-1
      completely, even longer treatment may be needed because of the possible existence
      of undetected viral compartments or sanctuary sites.

PMID- 9144291
TI  - Segmental regulation of Hoxb-3 by kreisler.
AB  - Hox genes control regional identity during segmentation of the vertebrate
      hindbrain into rhombomeres. Here we use transgenic analysis to investigate the
      upstream mechanisms for regulation of Hoxb-3 in rhombomere(r)5. We identified
      enhancers from the mouse and chick genes sufficient for r5-restricted expression.
      Sequence comparisons revealed two blocks of similarity (of 19 and 45 base pairs),
      which each contain in vitro binding sites for the kreisler protein (Kmrl1), a
      Maf/b-Zip protein expressed in r5 and r6 (ref. 4). Both sites are required for r5
      activity, suggesting that Hoxb-3 is a direct target of kreisler. Multimers of the
      19-base-pair (bp) block recreate a Krml1-like pattern in r5/r6, but the 45-bp
      block mediates expression only in r5. Therefore elements within the 45-bp block
      restrict the response to Krml1. We identified additional sequences that contain
      an Ets-related activation site, required for both the activation and restriction
      to r5. These studies demonstrate that Krml1 directly activates expression of Hoxb
      3 in r5 in combination with an Ets-related activation site, and suggest that
      kreisler plays a primary role in regulating segmental identity through Hox genes.

PMID- 9144292
TI  - Sex lethal controls dosage compensation in Drosophila by a non-splicing
      mechanism.
AB  - Dosage compensation in Drosophila requires the male-specific lethal (msl)
      proteins (MSL) to make gene expression from the single male X chromosome
      equivalent to that from both female X chromosomes. Expression of ms12 is
      repressed post-transcriptionally by Sex lethal (SXL), a female-specific RNA
      binding protein that regulates alternative splicing in the sex-determination
      hierarchy. Although msl2 RNA is alternatively spliced in males and females, this
      does not alter its coding potential and splicing is not required for male
      specific expression of MSL2 protein. Instead, our results suggest that the
      association of SXL protein with multiple sites in the 5' and 3' untranslated
      regions of the mx12 transcript represses its translation in females. Thus, this
      well characterized alternative splicing factor regulates at least one target
      transcript by a distinct mechanism.

PMID- 9144293
TI  - Homotypic vacuolar fusion mediated by t- and v-SNAREs.
AB  - Membrane fusion is necessary both in the eukaryotic secretory pathway and for the
      inheritance of organelles during the cell cycle. In the secretory pathway,
      heterotypic fusion takes place between small transport vesicles and organelles.
      It requires N-ethylmaleimide-sensitive fusion protein (NSF/Sec18p), soluble NSF
      attachment proteins (SNAPs/Sec17p) and SNAP receptors (SNAREs). SNAREs are
      integral membrane proteins (v-SNAREs on vesicles, t-SNAREs on the target
      organelles) and are thought to provide specificity to the fusion process. It has
      been suggested that Sec17p and Sec18p bind to v-SNARE/t-SNARE complexes and
      mediate the membrane fusion event. Homotypic fusion of yeast vacuoles also
      requires Sec17p and Sec18p (ref. 6), but in vitro they are needed only to 'prime'
      the vacuoles, not for subsequent docking or fusion. It has been unclear whether
      these reactions involve SNAREs that are similar to those previously identified in
      heterotypic fusion systems and, hence, whether the actions of Sec18p/NSF and
      Sec17p/alpha SNAP in these systems can be compared. Here we identify typical v-
      and t-SNAREs on the yeast vacuolar membrane. Although both are normally present,
      vacuoles containing only the v-SNARE can fuse with those containing only the t
      SNARE. Vacuoles containing neither SNARE cannot fuse with those containing both,
      demonstrating that docking is mediated by cognate SNAREs on the two organelle
      membranes. Even when t- and v-SNAREs are on separate membranes, Sec17p and Sec18p
      act at the priming stage. Their action is not required at the point of assembly
      of the SNARE complex, nor for the fusion event itself.

PMID- 9144294
TI  - Regulation of gene expression by small molecules.
AB  - Small molecules that target specific DNA sequences have the potential to control
      gene expression. Ligands designed for therapeutic application must bind any
      predetermined DNA sequence with high affinity and permeate living cells.
      Synthetic polyamides containing N-methylimidazole and N-methylpyrrole amino acids
      have an affinity and specificity for DNA comparable to naturally occurring DNA
      binding proteins. We report here that an eight-ring polyamide targeted to a
      specific region of the transcription factor TFIIIA binding site interferes with
      5S RNA gene expression in Xenopus kidney cells. Our results indicate that pyrrole
      imidazole polyamides are cell-permeable and can inhibit the transcription of
      specific genes.

PMID- 9144295
TI  - Crystal structure of the obese protein leptin-E100.
AB  - Mutations in the obese gene (OB) or in the gene encoding the OB receptor(OB-R)
      result in obesity, infertility and diabetes in a variety of mouse phenotypes. The
      demonstration that OB protein (also known as leptin) can normalize body weight in
      ob/ob mice has generated enormous interest. Most human obesity does not appear to
      result from a mutant form of leptin: rather, serum leptin concentrations are
      increased and there is an apparent inability to transport it to the central
      nervous system (CNS). Injection of leptin into the CNS of overfed rodents
      resistant to peripheral administration was found to induce biological activity.
      Consequently, for the leptin to act as a weight-lowering hormone in human
      obesity, it appears that appropriate concentrations must be present in the CNS.
      This places a premium on understanding the structure of the hormone in order to
      design more potent and selective agonists. Here we report the crystal structure
      at 2.4A resolution of a human mutant OB protein (leptin-E100) that has comparable
      biological activity to wild type but which crystallizes more readily. The
      structure reveals a four-helix bundle similar to that of the long-chain helical
      cytokine family.

PMID- 9144296
TI  - Gene therapy: basic concepts and applications in gastrointestinal diseases.
AB  - Molecular analyses have become an integral part of biomedical research as well as
      clinical medicine. The definition of the molecular and genetic basis of many
      human diseases has led not only to a better understanding of their pathogenesis,
      but has in addition offered new perspectives for their diagnosis, therapy, and
      prevention. Genetically, human diseases can be classified as monogenetic, complex
      genetic, and acquired genetic diseases. Based on this genetic classification,
      gene therapy involves four concepts: gene substitution, gene augmentation, block
      of gene expression or function as well as somatic transgene vaccination. Despite
      exciting recent developments, various delivery, targeting, and safety aspects
      need to be addressed before gene therapy will enter clinical practice. Clearly,
      molecular diagnosis and gene therapy of gastrointestinal diseases will be
      increasingly part of our patient management, complementing existing diagnostic,
      therapeutic, and preventive strategies.

PMID- 9144297
TI  - Pancreatitis-associated protein in patients with celiac disease: serum levels and
      immunocytochemical localization in small intestine.
AB  - Since PAP is a stress protein expressed in human pancreas during pancreatitis but
      also constitutively synthesized in the small intestine, we looked whether its
      expression would be altered in patients with celiac disease. Serum PAP
      concentrations were determined consecutively in 54 patients with celiac disease
      on a free diet (group A), in 47 patients with celiac disease on a gluten-free
      diet (group B), in 22 patients with other intestinal pathologies but with normal
      intestinal mucosa (group C), in 14 patients with retarded growth, no
      gastrointestinal disease and normal intestinal mucosa (group D), and in 17
      controls (group E). Serum PAP levels (ng/ml) were significantly higher in group A
      (127.3 +/- 56.8) than in the other groups (B: 47.2 +/- 20.5; C: 51.5 +/- 32.2; D:
      47 +/- 22.8; E: 27.6 +/- 9.0), which were not different from each other. In group
      A, a positive correlation was observed between serum PAP values and antigluten
      antibody levels (vs. AGA IgG r = 0.58, p < 0.001; vs. AGA IgA r = 0.66, p <
      0.001). Furthermore, 12 patients from group A were evaluated after 10-12 months
      of gluten-free diet and in all of them PAP serum concentration had decreased
      (mean +/- SE before the diet 122.5 +/- 36.4, after the diet 48.7 +/- 13.7, p <
      0.0001). In addition, we performed an immunocytochemical study to localize PAP in
      the intestinal mucosa of patients from all groups except E. PAP was localized to
      the Paneth cells and to some globet cells, in patients with mucosal atrophy as
      well as in those with normal mucosa with no obvious quantitative difference. We
      concluded that in patients with celiac disease the active phase of the disease
      was accompanied by an increased serum concentration of PAP. Further studies are
      necessary to understand the mechanism leading to PAP elevation in the serum of
      patients with celiac disease.

PMID- 9144298
TI  - Regulation of cholecystokinin release and transcription in a rat without gene
      expression of cholecystokinin-A receptor.
AB  - An Otsuka Long-Evans Tokushima Fatty (OLETF) rat does not possess cholecystokinin
      (CKK)-A receptor gene expression because of a genetic abnormality. We examined
      the CCK release and its transcription in OLETF rats in comparison with control
      (Long-Evans-Tokushima-LETO) rats. Animals at 5-6 and 24-25 weeks of age were
      used. The level of CCK mRNA and CCK concentration in the small intestinal mucosa,
      and the level of CCK-A receptor mRNA in the pancreas were examined. To examine
      CCK release, rats were prepared with external bile and pancreatic fistulae. The
      basal plasma levels of CCK and those at 2 h after bile-pancreatic juice diversion
      were measured by radioimmunoassay. The levels of CCK mRNA, and tissue CCK
      concentration increased significantly with age in both strains, but the values in
      OLETF rats were significantly lower than those in LETO rats. The CCK-A receptor
      mRNA level also increased with age in LETO rats. The plasma CCK concentration was
      significantly increased by bile-pancreatic juice diversion regardless of age and
      strain; however, the level of plasma CCK in OLETF rats at 24-25 weeks of age was
      significantly lower than that of LETO rats. It is suggested that the long-term
      defect of CCK-A receptor may decrease CCK release and transcription.

PMID- 9144299
TI  - Oesophageal acid and salivary secretion: is chewing gum a treatment option for
      gastro-oesophageal reflux?
AB  - The presence of acid in the oesophagus has been shown to stimulate salivary
      secretion, but the relevance of this oesophago-salivary reflex for acid clearance
      in physiological and pathological gastro-oesophageal reflux (GOR) is unknown.
      This study was designed to investigate the interrelation between oesophageal acid
      and both resting and stimulated salivary secretion. In 10 healthy volunteers, the
      acid clearance times after bolus infusion of 20 ml of 0.1 N hydrochloric acid
      were measured by means of ambulatory oesophageal pH monitoring. With a constant
      swallowing rate and resting salivary flow, the acid clearance time was
      significantly longer with dry as opposed to wet swallows (12.6 +/- 2.6 vs. 6.9 +/
      1.9 min; p = 0.01). When the salivary flow was doubled by chewing a gum base
      (26.0 +/- 3.4 vs. 13.2 +/- 2.0 ml/15 min; p = 0.005), the acid clearance time was
      markedly shortened (6.9 +/- 1.9 vs. 2.3 +/- 0.2 min; p = 0.02). As compared with
      water control, salivary flow, pH, and protein content were not affected by a
      bolus infusion of hydrochloric acid. This was true both for resting and gum
      stimulated salivary secretion. Our study suggests that an oesophago-salivary
      reflex becomes effective only in prolonged episodes of GOR. This may explain why
      the water brash phenomenon is not regularly experienced by all reflux patients.
      Our study also suggests that chewing gum might be a non-pharmacological treatment
      option for some patients with symptomatic GOR.

PMID- 9144300
TI  - Proximal gastric motility functions are normal in severe obesity.
AB  - The role of altered gastric motor functions for the development of obesity is
      still unclear. In this study, we investigated whether severe obesity is related
      to gastric dysfunctions or to abnormal perception in response to distension. 31
      obese patients and 20 healthy volunteers were studied using an electronic
      barostat. Basal gastric tone, gastric accommodation, and perception in response
      to distension were not altered in obese patients. The median minimal distending
      pressure, reflecting the intra-abdominal pressure, was significantly elevated in
      obese patients, being 12 versus 7 mm Hg, respectively (p < 0.0001). We conclude
      that the proximal gastric motility, including perception and accommodation in
      response to intragastric distension, is not impaired in severe obesity. Whether
      disturbances of gastric reflex relaxation in response to a meal are involved in
      the pathogenesis of obesity remains to be established.

PMID- 9144301
TI  - Rapid expression and specific localization of tenascin in gastric ulcer healing
      in rats.
AB  - This study was done to investigate the gene expression and localization of
      tenascin in ulcerated gastric tissues during the healing process with Northern
      blot analysis and immunohistochemical technique. Gastric ulcers in rats were
      produced by acetic acid. Tenascin mRNA levels in the ulcerated tissue were
      significantly increased in a biphasic manner (12 h and day 5), preceding the
      increase in collagen type IV and laminin mRNA levels, and returned to control
      levels on day 11. In intact tissues, tenascin was mainly localized in the
      basement membrane above the proliferative zone, in contrast to the predominant
      localization of collagen type IV and laminin below the proliferative zone. On the
      ulcer margin from 12 h to day 5, tenascin was abundantly observed in the lamina
      propria around nonproliferating new epithelial cells, but collagen type IV and
      laminin were not seen in this lamina propria. On day 7, tenascin, expressed in
      the lamina propria, was replaced by collagen type IV and laminin. Thus, the rapid
      expression and unique localization of tenascin suggest the important role of
      tenascin in gastric ulcer healing.

PMID- 9144302
TI  - Effect of quinacrine, a phospholipase A2 inhibitor on stress and chemically
      induced gastroduodenal ulcers.
AB  - Quinacrine, a phospholipase A2 inhibitor, has been studied for its ability to
      inhibit gastric secretion and to protect the gastric and duodenal mucosa against
      chemically and stress-induced ulcers. Acid secretion studies were undertaken in
      pylorus-ligated rats with and without quinacrine treatment. Experimental gastric
      lesions were induced by water-immersion restraint stress, indomethacin and 80%
      ethanol in rats; whereas duodenal ulcers were produced by treatment of rats with
      cysteamine. The level of nonprotein sulfhydryl compounds and gastric wall mucus
      were also measured in the glandular stomach of the rats following ethanol-induced
      gastric lesions. The results of this study demonstrate that quinacrine produces a
      dose-dependent inhibition of gastric acid secretion in rats. Pretreatment with
      quinacrine significantly attenuated the formation of stress-, indomethacin- and
      ethanol-induced gastric lesions. Quinacrine also protected intestinal mucosa
      against cysteamine-induced duodenal ulcers. The antiulcer activity of quinacrine
      was associated with appreciable inhibition of ethanol-induced depletion of
      nonprotein sulfhydryls and gastric wall mucus. These findings point towards the
      mediation of sulfhydryls in quinacrine-induced gastrointestinal cytoprotection.
      In conclusion, this study demonstrates that quinacrine possesses significant
      antiulcer and cytoprotective activity against various experimentally induced
      gastroduodenal lesions. Although the mechanism of action of quinacrine requires
      further evaluation, the experimental observations derived from this study may
      have future clinical relevance and therefore deserve to be investigated
      thoroughly.

PMID- 9144303
TI  - Alterations in porcine gastric mucin during the development of experimental
      ulceration.
AB  - Bile duct ligation in the pig results in ulceration of the pars oesophagea
      (oesophagogastric junction) within 48 h with 100% reproducibility. This work
      describes novel observations made during development of such ulcers using an
      endoscope introduced at intervals postoperatively via a Thomas gastric cannula.
      Macroscopic and histological changes were recorded and compared with quantitative
      and qualitative changes in crude mucus scrapings and purified mucins. Crude mucus
      scrapings of the cardiac gland region had a higher protein content in the
      ulcerated states than in the normals. After bile duct ligation, the (degraded)
      mucin glycopeptide/total protein ratio was higher in partially purified mucus
      from pre-ulcerated and ulcerated stomachs as compared with normal samples. The
      quantity of purified mucin was less in samples from ulcerated stomachs, and the N
      acetylgalactosamine and fucose contents were also decreased. It is possible that
      these changes resulted in the failure of the mucus barrier and the development of
      oesophagogastric junction ulceration.

PMID- 9144304
TI  - Flavonoid-induced gastroprotection in rats: role of blood flow and leukocyte
      adherence.
AB  - To elucidate the mechanisms of flavonoid-induced protection against nonsteroidal
      anti-inflammatory drug (indomethacin)-induced acute gastric damage, the effects
      of 5-methoxyflavone and 5-methoxyflavanone on the gastric vasculature were
      compared both in vivo (using laser Doppler flowmetry in anesthetized rats) and in
      vitro on rat superior mesenteric arteries. The effects of the compounds on
      indomethacin-induced leukocyte adherence to mesenteric venules were investigated
      by intravital videomicroscopy. Oral 5-methoxyflavone reduced indomethacin-induced
      macroscopic damage by 38 to 99% (ED50 = 5.5 mg/kg). Damage was not significantly
      reduced by 5-methoxyflavanone. Light microscopy studies also demonstrated a
      reduction in damage severity. 5-Methoxyflavone, but not 5-methoxyflavanone,
      increased the gastric conductance significantly. The effects on isolated
      mesenteric arteries correlated with the effects on in vivo conductance. Finally,
      indomethacin-induced leukocyte adherence was inhibited to a greater extent by 5
      methoxyflavone than by 5-methoxyflavanone. In conclusion, the flavonoid 5
      methoxyflavone provides gastroprotection against nonsteroidal anti-inflammatory
      drug-induced gastric damage. A structurally similar compound, 5-methoxyflavanone,
      demonstrated minimal gastroprotective activity, suggesting that the double bond
      of 5-methoxyflavone is required for biological activity. The finding that 5
      methoxyflavone (but not 5-methoxyflavanone) significantly increased gastric
      vascular perfusion and reduced leukocyte adherence to mesenteric venules suggests
      that these mechanisms may contribute to the flavonoid's gastroprotective
      activity.

PMID- 9144305
TI  - Comparative analysis of adult and fetal human small intestinal microvilli.
AB  - The aim was to study the development of human small intestinal microvillus
      membranes. We compared the protein patterns of human fetal and adult small
      intestinal microvillus membranes using the high-resolution technique of sodium
      dodecyl sulphate-polyacrylamide gel electrophoresis. We also examined the
      synthesis of brush border membrane proteins from the adult small intestine using
      small intestinal biopsy organ culture 35S-methionine uptake and subsequent gel
      electrophoresis. We observed that the fetal and colonic microvillus membranes
      were similar, but differed in certain respects from adult small intestinal
      microvillus membranes. The jejunal biopsy organ culture revealed that synthesised
      brush border membrane proteins could be recognized by gel electrophoresis.

PMID- 9144306
TI  - Phospholipid profile and fatty acid composition of rat cecal mucosa in relation
      to intestinal resection.
AB  - In this study we examined the effect of distal small bowel resection (DSBR) on
      the phospholipid composition of rat cecal mucosa. Three groups of animals were
      used: sham-operated, and 50% and 75% DSBR. The fatty acid composition of
      phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylinositol
      (PI), lysophosphatidylcholine (LPC) and sphingomyelin (SM) was also determined.
      PE was the predominant phospholipid, together with PC, in the 3 groups of
      animals. Both phospholipids accounted for more than 60% of the total
      phospholipids. DSBR affected the phospholipid profile of the cecal mucosa. Thus
      the ratio PC/PE was increased in the 75% resected animals. A decrease in the
      proportion of LPC and LPE was observed after DSBR, and the PI proportion was not
      changed in the resected rats. The phospholipid/cholesterol molar ratio was not
      modified as a consequence of DSBR. Different fatty acid composition changes in
      the cecal phospholipid subclasses were observed after DSBR. The PC fraction
      contained the highest amounts of saturated fatty acids in all the animal groups.
      Linoleic and arachidonic acids were found in all phospholipid fractions in the 3
      groups of animals except in the SM of sham rats and in the LPC of resected rats,
      in which values of arachidonic acid were not found. All these changes might be
      involved in physicochemical, biochemical and/or functional adaptations observed
      in the cecum after DSBR.

PMID- 9144307
TI  - Colonic mucin discharge by a cholinergic agonist, prostaglandins, and peptide YY
      in the isolated vascularly perfused rat colon.
AB  - The model of the isolated, vascularly perfused rat colon was assessed in the
      present study to investigate the nervous, hormonal, and local/paracrine pathways
      involved in colonic mucin secretion. A colonic loop was perfused via the superior
      mesenteric artery with a Krebs-Henseleit buffer containing 25% washed bovine
      erythrocytes at a rate of 2.5 ml/min. After a 10-min control period, each
      compound to be tested was infused intra-arterially for 30 min. Tissue samples
      from the proximal and midsegments of the perfused rat colon were then fixed and
      stained for mucus cell count. Intra-arterial administration of bethanechol evoked
      a concentration-dependent decrease in the number of stained mucus cells per crypt
      section over the range 2 x 10(-6) to 2 x 10(-4) M: 16.6 +/- 1.4 stained mucus
      cells per crypt in the midportion of the perfused rat colon (n = 5) with
      bethanechol 2 x 10(-4) M versus 28.8 +/- 1.5 for controls (n = 6). After infusion
      of 1.25 and 2.5 microM 16,16-dimethyl prostaglandin E2 (dmPGE2), the number of
      stained mucus cells per crypt section was significantly reduced: 21.6 +/- 0.6 (n
      = 6) and 20.6 +/- 1.4 (n = 7), respectively. An increase in the number of
      cavitated mucus cells was also observed (22.1 +/- 6.7 and 38.5 +/- 4.1% of
      cavitated mucus cells in the midsegment of the perfused rat colon with 1.25 and
      2.5 microM dmPGE2, respectively, vs. 12.3 +/- 4.1% for controls). In contrast,
      prostaglandin F2alpha did not significantly affect mucus discharge from colonic
      cells. Peptide YY (10(-10), 10(-9) and 10(-8) M) induced a dose-dependent
      increase in the percentage of cavitated mucus cells (16.7 +/- 2.8, 23.1 +/- 4.2,
      and 31.2 +/- 3.4% of cavitated mucus cells in the midsegment, respectively). The
      proximal and midsegments of the perfused rat colon were equally sensitive to each
      secretagogue. CONCLUSION: In the isolated, vascularly perfused rat colon, mucus
      cells strongly respond to the well-known mucin secretagogues, bethanechol and
      dmPGE2. This approach has already led to the identification of a novel stimulant
      of mucin secretion: peptide YY. Our ex vivo model, in which goblet cells are
      submitted to well-defined luminal and blood-borne stimuli is, therefore, reliable
      to investigate the nervous, hormonal, and local/paracrine pathways involved in
      the colonic mucin secretion.

PMID- 9144308
TI  - Assessment of disease activity in ulcerative colitis by faecal calprotectin, a
      novel granulocyte marker protein.
AB  - This study comprised 62 outpatients with ulcerative colitis who underwent 64
      colonoscopies. The disease activity was evaluated according to endoscopic and
      histological criteria. The results revealed a significant correlation between
      both the endoscopic as well as the histological gradings of disease activity and
      faecal calprotectin. The median faecal calprotectin levels in the control group
      (6 mg/l) and in the patients with no or low disease activity (11.5 mg/l) were
      significantly different (p < 0.0001). The median calprotectin level among
      patients with active disease was 68 mg/l which was significantly different from
      the latter group (p < 0.0001). Furthermore, we suggest that the degree of
      inflammation rather than the extent of the disease determined the faecal
      calprotectin levels. In conclusion, assessment of faecal calprotectin seems to be
      a marker of disease activity in patients with ulcerative colitis.

PMID- 9144309
TI  - Microheterogeneity of rat serum alkaline phosphatase in fasting state:
      characterization of two duodenal alkaline phosphatase glycoforms.
AB  - Using concanavalin A-Sepharose affinity chromatography (Con A) we found that the
      serum of normal fasted adult rats contains two alkaline phosphatase (APase)
      glycoforms, one weakly bound (II) and the other strongly (III) bound to the
      column. Both serum APase glycoforms had an apparent molecular mass of 163 kD on
      Sepharose CL-6B and 118 kD on SDS-PAGE under nondenaturing conditions. We
      consider the molecular forms as dimeric, since monomers of 60.3 and 58.5 kD for
      the Con A weakly and strongly bound glycoform, respectively, were obtained.
      However, these two dimeric glycoforms were different in their pH optimum,
      affinity to p-nitrophenyl phosphate as substrate, the degree of L-phenylalanine
      inhibition and relative thermostability. Judging by the relative thermostability
      and by L-phenylalanine inhibition, it seems that both serum APase glycoforms in
      fasted rats are mainly of duodenal mucosal cell origin. The Con A weakly bound
      (II) glycoform could be derived from the cytosol, and the Con A strongly bound
      (III) one from both the cytosolic and membranous fractions of duodenal mucosal
      cells. However, in addition to the heat-stable component, the Con A strongly
      bound serum APase glycoform also contains a minor heat-labile and L-phenylalanine
      resistant component which could be of nonspecific tissue origin since such a
      fraction was not discovered by us in rat duodenal mucosal cells.

PMID- 9144310
TI  - Acute hepatic failure following transcatheter arterial embolization for the
      treatment of hepatocellular carcinoma.
AB  - We conducted a retrospective analysis to evaluate the risk factors associated
      with the occurrence of acute hepatic failure following transcatheter arterial
      embolization (TAE) for hepatocellular carcinoma. From 1984 to 1993 we performed a
      total of 623 embolization procedures in 369 patients with both hepatocellular
      carcinoma and chronic liver disease. Within 2 weeks after TAE, 13 patients (2.1%)
      experienced hepatic failure as characterized by a rapid increase in serum
      bilirubin levels and the development of hepatic encephalopathy of grade 2 or
      higher. These results indicated that the following are risk factors for acute
      hepatic failure after TAE: poor hepatic functional reserve; high-dose infusion of
      chemotherapeutic agents, and a history of multiple embolization procedures.

PMID- 9144311
TI  - Motility in irritable-bowel syndrome.

PMID- 9144312
TI  - Modulation of cytosolic and nuclear Ca2+ and Na+ transport by taurine in heart
      cells.
AB  - The effect of taurine on the different types of ionic currents appears to depend
      on [Ca]o and [Ca]i and may also vary accordingly to tissue or cell type studied.
      Using microfluorometry and Ca2+ imaging techniques, short-term exposure (5-10
      min) of single heart cells to taurine was found to increase total intracellular
      free Ca2+ in a concentration-dependent manner. However, long-term exposure of
      heart myocytes to taurine was found to decrease both nuclear and cytosolic Ca2+
      without significantly changing either nuclear or cytosolic Na+ levels, as
      measured by 3-dimensional Ca2+ and Na+ confocal imaging techniques. Long-term
      exposure to taurine was found to prevent cytosolic and nuclear increases of Ca2+
      induced by permanent depolarization of heart cells with high [K]o. This
      preventive effect of taurine on nuclear Ca2+ overload was associated with an
      increase of both cytosolic and nuclear free Na+. Thus, the effect of long-term
      exposure to taurine on intranuclear Ca2+ overload in heart cells seems to be
      mediated via stimulation of sarcolemmal and nuclear Ca2+ outflow through the Na+
      Ca2+ exchanger.

PMID- 9144313
TI  - The association of tubulin carboxypeptidase activity with microtubules in brain
      extracts is modulated by phosphorylation/dephosphorylation processes.
AB  - Tubulin carboxypeptidase, the enzyme which releases the COOH terminal tyrosine
      from the alpha-chain of tubulin, remains associated with microtubules through
      several cycles of assembly/disassembly (Arce CA, Barra HS: FEBS Lett 157: 75-78,
      1983). Here, we present evidence indicating that in rat brain extract the
      carboxypeptidase/microtubules association is regulated by the relative activities
      of endogenous protein kinase(s) and phosphatase(s) which seem to determine the
      phosphorylation state of the enzyme (or another entity) and in some way the
      affinity of the enzyme for microtubules. The presence of 2.5 mM ATP during the in
      vitro microtubule formation resulted in a low recovery of carboxypeptidase
      activity in the microtubule fraction. This ATP-induced effect was not due to
      alteration of the enzyme activity or to inhibition of microtubule assembly but to
      a decrease of the association of the enzyme with microtubules. We found that the
      ATP-induced effect was not mediated by modifications on the microtubules but,
      presumably, on the enzyme molecule. The non-hydrolyzable ATP analogue, AMP-PCP,
      did not reproduce the effect of ATP. The inclusion of phosphatase inhibitors in
      the homogenization buffer also led to a decrease in the amount of tubulin
      carboxypeptidase associated with microtubules. Finally, we found that, in
      concordance with the mechanism hypothesized, the magnitude of the
      carboxypeptidase/microtubule association correlated well with the different
      incubation conditions created to favor maximal, minimal or intermediate protein
      phosphorylation states.

PMID- 9144314
TI  - Alterations in Ca2+-ATPase activity and calcium-binding protein regucalcin mRNA
      expression in the kidney cortex of rats with saline ingestion.
AB  - The alteration in calcium metabolism in rats ingested with saline was
      investigated. Rats were freely given saline as drinking water for 2 and 7 days.
      Calcium concentration in the serum was significantly elevated by saline ingestion
      for 2 and 7 days, while serum inorganic phosphorus concentration was not altered.
      Serum urea nitrogen concentration was significantly increased by saline ingestion
      for 7 days. Calcium content in the femoral-diaphyseal and metaphyseal tissues was
      not altered by saline ingestion for 7 days. Calcium content in the kidney cortex
      was significantly elevated by saline ingestion for 7 days. Ca2+-ATPase activity
      in the basolsateral membranes of kidney cortex was clearly increased by saline
      ingestion for 2 and 7 days. The enzyme activity was not altered by the addition
      of sodium chloride (10(-3) and 10(-2) M), parathyroid hormone (10(-7) and 10(-6)
      M), and calcitonin (3 x 10(-8) and 3 x 10(-7) M) in the enzyme reaction mixture.
      A calcium-binding protein regucalcin mRNA expression in the kidney cortex was
      markedly suppressed by saline ingestion for 7 days, although such a suppression
      was not seen for 2 days. These results suggest that saline ingestion causes the
      disturbance of calcium transport system in the kidney cortex of rats, and that
      the renal disorder may induce hypercalcemia.

PMID- 9144316
TI  - Examination of the molecular basis for the lack of alphaB-crystallin expression
      in L929 cells.
AB  - We have previously shown that murine L929 cells do not express the small heat
      shock protein alphaB-crystallin upon exposure to thermal stress (Mol Cell Biochem
      155: 51-60, 1996). In these studies, we demonstrate that L929 cells also fail to
      express alphaB-crystallin upon exposure dexamethasone, whereas NIH 3T3 and Swiss
      3T3 murine cells exhibit alphaB-crystallin expression under identical conditions.
      Mobility shift assays demonstrated heat-inducible binding, presumably by heat
      shock factor(s), to an alphaB-crystallin heat shock element (HSE) oligomeric
      sequence in total cellular extracts from L929 cells. Transient transfection of a
      plasmid containing the alphaB-crystallin promoter linked to a CAT reporter gene
      exhibited heat-inducible expression in L929 cells. In addition, L929 cells stably
      transfected with a plasmid containing the complete alphaB-crystallin gene showed
      expression of this gene following heat shock. The presence of the endogenous
      alphaB-crystallin gene was detected by Southern blot hybridization of genomic
      L929 DNA, and sequence analysis revealed identical nucleotide structure to
      published murine sequences throughout the entire promoter. Treatment of L929
      cells with 5-azacytidine enabled heat-inducible expression of alphaB-crystallin
      from the endogenous gene, however, methylation of the putative heat shock element
      (HSE) and flanking promoter sequences of L929 cell genomic DNA was not detected.
      In vivo genomic footprinting demonstrated constitutive binding to the endogenous
      HSE of the alphaB-crystallin promoter in L929, L929/alphaB-crystallin
      transfectant cells, and Swiss 3T3 cells during unstressed and heat stressed
      conditions. Therefore, the genomic alphaB-crystallin HSE region in L929 cells
      appears to be available for binding of putative transcription factors, but
      methylation in other regions of the gene or genome repress the expression of
      alphaB-crystallin in L929 cells. In vitro culture of L929 cells appears to have
      rendered the alphaB-crystallin gene loci inactive through methylation, thus
      providing a unique system by which to study the function of transfected small
      heat shock proteins.

PMID- 9144315
TI  - Differential effect of glucose deprivation on MAPK activation in drug sensitive
      human breast carcinoma MCF-7 and multidrug resistant MCF-7/ADR cells.
AB  - We have investigated the effect of glucose deprivation treatment on the
      activation of mitogen activated protein kinases (MAPKs) in the drug-sensitive
      human breast carcinoma cells (MCF-7) and its drug resistant variant (MCF-7/ADR)
      cells. Western blots and in-gel kinase assays showed that glucose free medium was
      a strong stimulus for the activation of MAPK in MCF-7/ADR cells. No activation
      was seen in MCF-7 cells. MAPK was activated within 3 min of being in glucose free
      medium and it remained activated for over 1 h in MCF-7/ADR cells. After being
      returned to complete medium, 1 h was required for the MAPK to become deactivated.
      To investigate whether alternative sources of ATP could inhibit glucose
      deprivation induced MAPK activation, we added glutamine and glutamate to glucose
      deprived medium. The addition of glutamine did not reverse glucose deprivation
      induced MAPK activation in MCF-7/ADR cells. The addition of glutamate, however,
      decreased the MAPK activation and the length of time of activation. We observed
      an increase greater than three fold in MEK, Raf, Ras, and PKC activity with
      glucose deprivation in MCF-7/ADR cells. This suggests that glucose deprivation
      induced MAPK activation is mediated through this signal transduction pathway.

PMID- 9144317
TI  - Effects of advanced glycation end-products on the proliferation and
      differentiation of osteoblast-like cells.
AB  - Two different lines of osteoblast-like cells were used to investigate the effect
      of advanced glycation end-products of bovine serum albumin on cell proliferation
      and differentiation. These parameters were found to be both dose- and time
      dependent. Cell proliferation remained unchanged after a 24 h incubation period,
      it increased after intermediate periods of incubation with advanced glycation end
      products, but was found to be depressed after several days incubation. Cellular
      alkaline phosphatase activity followed a similar pattern: an initial increase
      induced by advanced glycation end-products was generally followed, after
      relatively long incubation periods, by a slight but significant decrease in this
      parameter. 45Ca2+ uptake was only significantly inhibited by advanced glycation
      end-products after 24 h incubation. These results suggest that advanced glycation
      end-products directly regulate osteoblast proliferation and differentiation in a
      dose and time dependent manner.

PMID- 9144318
TI  - Influence of vanadate on glycolysis, intracellular sodium, and pH in perfused rat
      hearts.
AB  - Vanadium compounds have been shown to cause a variety of biological and metabolic
      effects including inhibition of certain enzymes, alteration of contractile
      function, and as an insulin like regulator of glucose metabolism. However, the
      influence of vanadium on metabolic and ionic changes in hearts remains to be
      understood. In this study we have examined the influence of vanadate on glucose
      metabolism and sodium transport in isolated perfused rat hearts. Hearts were
      perfused with 10 mM glucose and varying vanadate concentrations (0.7-100 microM)
      while changes in high energy phosphates (ATP and phosphocreatine (PCr)),
      intracellular pH, and intracellular sodium were monitored using 31P and 23Na NMR
      spectroscopy. Tissue lactate, glycogen, and (Na+, K+)-ATPase activity were also
      measured using biochemical assays. Under baseline conditions, vanadate increased
      tissue glycogen levels two fold and reduced (Na+, K+)-ATPase activity.
      Significant decreases in ATP and PCr were observed in the presence of vanadate,
      with little change in intracellular pH. These changes under baseline conditions
      were less severe when the hearts were perfused with glucose, palmitate and beta
      hydroxybutyrate. During ischemia vanadate did not limit the rise in intracellular
      sodium, but slowed sodium recovery on reperfusion. The presence of vanadate
      during ischemia resulted in attenuation of acidosis, and reduced lactate
      accumulation. Reperfusion in the presence of vanadate resulted in a slower ATP
      recovery, while intracellular pH and PCr recovery was not affected. These results
      indicate that vanadate alters glucose utilization and (Na+, K+)-ATPase activity
      and thereby influences the response of the myocardium to an ischemic insult.

PMID- 9144319
TI  - Deprivation of Na+, Ca2+ and Mg2+ from the extracellular solution increases
      cytosolic Ca2+ and stimulates catecholamine secretion from cultured bovine
      adrenal chromaffin cells.
AB  - We report here that exposing cultured chromaffin cells to a low ionic strength
      medium (with sucrose in place of NaCl to maintain osmolarity) can induce a marked
      elevation in cytosolic Ca2+ concentration ([Ca2+]i) and catecholamine (CA)
      release. To determine the underlying mechanism, we first studied the effects of
      low [Na+]o on single cell [Ca2+]i (using fluo-3 as Ca2+ indicator) and CA release
      from many cells. In a Mg2+ and Ca2+-deficient medium, lowering the external
      concentration of Na2+ ([Na+]o) evoked CA secretion preceded by a transitory
      [Ca2+]i rise, the amplitude of which was inversely related to [Na+]o. By
      contrast, in the presence of either [Ca2+]o (2 mM) and [Mg2+]o (1.4 mM) or
      [Mg2+]o alone (3.4 mM), lowering the ionic strength was without effect.
      Furthermore, in a physiologic [Na+]o, [Ca2+]o and [Mg2+]o medium, two or three
      consecutive applications of the cholinergic agonist oxotremorine-M (oxo-M)
      consistently evoked a substantial [Ca2+]i, rise. By contrast, consecutive
      applications of oxo-M in a Ca2+-deficient medium failed to evoke a rise in
      [Ca2+]i after the first exposure to the agonist. To clarify the underlying
      mechanism, we measured and compared the effects of low [Na+]o and the cholinergic
      agonists nicotine and oxo-M on changes in [Ca2+]i; we studied the effects of
      these agonists on both membrane potential, Vm (under current clamp conditions),
      and [Ca2+]i by single cell microfluorimetry (indo-1 as Ca2+ indicator). We
      observed that, in the presence of [Ca2+]o and [Mg2+]o, lowering [Na+]o had no
      effect on Vm. In a Ca2+-deficient medium, lowering [Na+]o depolarized the
      membrane from ca. -60 to -10 mV. As expected, we found that nicotine (10 microM)
      depolarized the membrane (from ca. -60 to -20 mV) and simultaneously evoked a
      substantial [Ca2+]i rise that was [Ca2+]o-dependent. However, contrary to our
      expectations, we found that the muscarinic agonist oxo-M (50 microM) also
      depolarized the membrane and induced an elevation in [Ca2+]i. Furthermore, both
      signals were blocked by D-tubocurarine, insinuating the nicotinic character of
      oxo-M in adrenal chromaffin cells from bovine. These results suggest that both
      nicotine and oxo-M stimulate Ca2+ entry, probably through voltage-gated Ca2+
      channels. We also show here that oxo-M (and not low [Na+]o) stimulates
      phosphoinositide turnover.

PMID- 9144320
TI  - A low molecular weight substance purified from human placenta inhibits cAMP
      dependent protein kinase and activates protein kinase C.
AB  - We have purified from human placenta a low molecular mass substance that inhibits
      cAMP-dependent protein kinase and activates protein kinase C. This protein kinase
      regulator was purified in three steps: (1) homogenizing placentas in
      chloroform/methanol and extracting the regulator into water; (2) eluting a strong
      anion exchange high performance liquid chromatography (HPLC) column with a
      quaternary gradient; and (3) eluting a reversed-phase HPLC column with a binary
      gradient. The regulator was found to be highly purified by HPLC, thin-layer
      chromatography (TLC) and laser desorption ionization mass spectrometry with a
      molecular mass of 703 Daltons by the latter procedure. The physical and
      biochemical properties of this protein kinase regulator suggest that it is a
      phospholipid but it did not co-elute by HPLC or by TLC with any of the known
      phospholipid activators of protein kinase C.

PMID- 9144321
TI  - Minimally modified low density lipoproteins induce aortic smooth muscle cell
      proliferation via the activation of mitogen activated protein kinase.
AB  - We have investigated the effects of modifying LDL by Cu++ and various hemoglobin
      preparations on aortic smooth muscle cell proliferation and on the activation of
      mitogen activated protein kinase. We found that at very low concentrations (10
      microg/ml), LDL modified by all of the above agonists markedly stimulated cell
      proliferation (5-10 fold). This was accompanied by a 2-3 fold stimulation in
      mitogen activated protein kinase (MAPK) activity. We conclude that modification
      of LDL under situations that are closer to those found in vivo (i.e. hypoxic
      conditions), may involve the activation of MAPK as a common biochemical mechanism
      of action. This in turn, contributes to aortic smooth muscle cell proliferation.

PMID- 9144322
TI  - Conversion of hydrophilic tubulin into a hydrophobic compound. Evidence for the
      involvement of membrane proteins.
AB  - Brain membranes contain tubulin that can be isolated as a hydrophobic compound by
      partitioning into Triton X-114. We have previously postulated: (a) that this kind
      of tubulin is a peripheral membrane protein that arises from microtubules that in
      vivo interact with membranes and (b) that the hydrophobic behaviour is due to the
      interaction of tubulin with a membrane component. Here we report the in vitro
      conversion of hydrophilic into hydrophobic tubulin by incubating microtubule
      associated proteins (MAPs) free taxol-stabilized microtubules with Triton X-100
      solubilized membranes. After incubation, the microtubules were sedimented,
      depolymerized and subjected to partition into Triton X-114. Part of the tubulin
      was isolated in the detergent phase and contained, as observed in native
      membranes, a high proportion of the acetylated isotype. Because of the high
      proportion of acetylated tubulin the 'in vitro' conversion resembles the 'in
      vivo' interaction. Electrophoretic analysis of the detergent phase shows, besides
      tubulin, two major protein bands of 29 and 100 kDa molecular mass. The ability of
      the solubilized membranes to convert hydrophilic into hydrophobic tubulin is
      greatly diminished if the solubilized membrane preparation is preincubated in the
      presence of trypsin or heated at 90 degrees C for 5 min, indicating that the
      membrane component that confers the hydrophobic behaviour to tubulin is of
      proteinaceous nature.

PMID- 9144323
TI  - Expression and regulation of mutant forms of cardiac TnI in a reconstituted
      actomyosin system: role of kinase dependent phosphorylation.
AB  - When phosphorylated, the inhibitory subunit of troponin (TnI) causes a loss in
      calcium sensitivity and a decrease in actomyosin ATPase. To examine this process,
      we bacterially expressed wild type TnI and TnI mutants in which serine 22 and 23,
      a putative protein kinase A (PKA) site, and threonine 143, a putative protein
      kinase C (PKC) site, were replaced by alanine S22A/23A and TI43A. PKA dependent
      phosphorylation was approximately 90% reduced in the S22A/23A mutant and
      unaffected in T143A. PKC dependent phosphorylation was markedly reduced in T 143A
      relative both to a wild type construct and to S22A/23A, although some residual
      phosphorylation (likely at sites other than T143) was seen. The calcium
      sensitivity (i.e. inhibition of actomyosin ATPase in the presence of EGTA) and
      regulation of the reconstituted actomyosin system was preserved in the absence of
      phosphorylation using wild type TnI or either mutant. Calcium sensitivity was
      decreased by both PKA and PKC with the wild type TnI but was unaffected by PKA
      when the S22A/23A mutant was employed and by PKC when the T143A mutant was
      reconstituted. The calcium dependency of the ATPase curve was substantially right
      shifted when PKC phosphorylated wild type TnI was employed for regulation, and
      this was markedly attenuated when T143 A was reassociated (although a slight
      rightward shift and a reduction in maximal ATPase activity was still seen). These
      data confirm that phosphorylation of TnI by regulatory kinases plays a major role
      in the regulation of myofibrillar ATPase. The N-terminal serines (22 and 23)
      appear to be uniquely important for the PKA response whereas threonine 143 is
      involved in the PKC response although other residues may also have functional
      significance.

PMID- 9144324
TI  - Modulation of glutathione level during butyrate-induced differentiation in human
      colon derived HT-29 cells.
AB  - Glutathione plays an important role in various cellular functions including cell
      growth and differentiation. In the present study, cell differentiation was
      induced by butyrate in human colon cell line HT-29 and cellular thiol status was
      assessed. It was observed that butyrate-induced differentiation was associated
      with decrease in cellular GSH level and this was prominent at early stages of
      differentiation. Buthionine sulfoximine (BSO), a specific cellular GSH depleting
      agent, did not induce differentiation in cells but potentiated the
      differentiation induced by butyrate. Both BSO and butyrate individually and
      together inhibited cell growth. These studies suggest that cellular GSH level is
      modulated in butyrate-induced differentiation and decrease of GSH at the initial
      stage might facilitate cellular differentiation.

PMID- 9144325
TI  - Characterization and localization of an ATP diphosphohydrolase activity (EC
      3.6.1.5) in sarcolemmal membrane from rat heart.
AB  - In the present report we describe an ATP diphosphohydrolase (apyrase EC 3.6.1.5)
      in rat cardiac sarcolemma. It is Ca2+ dependent and is insensitive to ouabain,
      orthovanadate, N-ethylmaleimide (NEM), lanthanum, and oligomycin that are
      classical ATPase inhibitors. Sodium azide that is a mitochondrial inhibitor at
      low concentrations, did not affect the enzyme activity at 5.0 mM or below. In
      contrast, at high concentrations (> 10 mM) sodium azide inhibited the enzyme.
      Levamisole, a specific inhibitor of alkaline phosphatase and P1, P5-di(adenosine
      5'-)pentaphosphate (Ap5A), a specific inhibitor of adenylate kinase did not
      inhibit the enzyme. Mercury chloride showed a parallel inhibition of the
      hydrolysis of both substrates of apyrase. Similar inhibition profiles are
      powerful evidence for a common catalytic site for the hydrolysis of both
      substrates. The enzyme has an optimum pH range of 7.5-8.0 and catalyzes the
      hydrolysis of triphospho- and diphosphonucleosides other than ATP or ADP. The
      apparent Km (Michaelis constant) and Vmax (maximal velocity) are 62.1 +/- 5.2
      microM and 1255.7 +/- 178 micromol inorganic phosphate liberated/min/mg with ATP
      and 59.4 +/- 4.3 microM and 269.2 +/- 39 micromol inorganic phosphate
      liberated/min/mg with ADP. Enzyme markers indicated that this apyrase is
      associated with the plasma membrane. A deposition of lead phosphate granules on
      the outer surface of the sarcolemmal vesicles was observed by electron microscopy
      in the presence of either ATP or ADP as substrate. It is suggested that the ATP
      diphosphohydrolase could regulate the concentration of extracellular adenosine,
      and thus is important in the control of vascular tone and coronary flow.

PMID- 9144326
TI  - Modifications induced by plasma of gestational hypertensive women on the Na+/K+
      ATPase obtained from human placenta.
AB  - In order to investigate the molecular mechanisms of the inhibition of Na+/K+
      ATPase in Gestational Hypertension (GH), we incubated Na+/K+-ATPase purified from
      human placenta of 6 healthy normotensive women with plasma from 6 GH women and 6
      healthy controls. We determined the enzyme activity by the method of Esman, and
      the anthroyl-ouabain-binding capacity, dissociation constant (Kd) and average
      lifetime values (tau) by the static and dynamic fluorescence of anthroyl-ouabain.
      The lipid annulus of the enzyme was studied by static and dynamic fluorescence of
      1-(4-trimethylaminophenyl)-6-phenyl-1,3,5- hexatriene (TMA-DPH). The addition of
      total and protein-free GH plasma to normal Na+/K+-ATPase significantly inhibited
      the enzymatic activity even at the lowest concentration studied (1:100), as well
      as the ouabain-binding capacity, Kd and tau. GH plasma significantly decreased
      the fluorescence polarization and lifetime values of TMA-DPH. These observations
      indicate that the inhibition caused by GH plasma on Na+/K+-ATPase might be due to
      a reduction of the number of active molecules or a modification of the ouabain
      binding site suggesting the existence of digitalis-like factor. A link between
      the modification of the lipid moiety of the enzyme and the Na+/K+-ATPase
      inhibition might be hypothesized.

PMID- 9144327
TI  - Tocotrienols from palm oil as effective inhibitors of protein oxidation and lipid
      peroxidation in rat liver microsomes.
AB  - Tocotrienols from palm oil showed significant ability to inhibit oxidative damage
      induced by ascorbate-Fe2+ and photosensitization, involving different mechanisms,
      in rat liver microsomes. The tocotrienol-rich fraction from palm oil (TRF), being
      tried as a more economical and efficient substitute for alpha-tocopherol, showed
      time- and concentration-dependent inhibition of protein oxidation as well as
      lipid peroxidation. It was more effective against protein oxidation. The extent
      of inhibition by TRF varied with different peroxidation products such as
      conjugated dienes, lipid hydroperoxides and thiobarbituric acid reactive
      substances (TBARS). Among the constituents of TRF, gamma-tocotrienol was the most
      effective followed by its alpha- and delta-isomers. In general, at a low
      concentration of 5 microM, TRF was able to prevent oxidative damage to
      significant extent (37% inhibition of protein oxidation and 27-30% of lipid
      peroxidation at 1 h of incubation). The protective ability of TRF (30.1% at 5
      microM with TBARS formation) was significantly higher than that of the dominant
      form of vitamin E, alpha-tocopherol (16.5% under same conditions). Hence our
      studies indicate that this fraction from palm oil can be considered as an
      effective natural antioxidant supplement capable of protecting cellular membranes
      against oxidative damage.

PMID- 9144328
TI  - A brain protein (P30) that immunoreacts with a polyclonal anti-pancreatic
      carboxypeptidase A antibody shows properties that are shared with tubulin
      carboxypeptidase.
AB  - A preparation of tubulin carboxypeptidase partially purified from bovine brain
      was found to contain a protein of molecular mass 30 kDa (P30) as determined by
      SDS-PAGE, that is recognized by a polyclonal anti-bovine pancreatic
      carboxypeptidase A. However, this protein is different from pancreatic
      carboxypeptidase A as judged by the isoelectric point and the pattern of peptides
      produced by trypsin digestion. The isoelectric point of P30 was similar to that
      found for tubulin carboxypeptidase (9 +/- 0.2). When the tubulin carboxypeptidase
      preparation was subjected to gel filtration chromatography under low salt
      concentration, P30 behaved as a protein of molecular mass 38 kDa whereas tubulin
      carboxypeptidase eluted at a position of 75 kDa molecular mass. However, when the
      chromatography was performed at relatively high salt concentration they behaved
      as proteins of 49 and 56 kDa, respectively. We considered that P30 may be an
      inactive monomeric form of the dimeric tubulin carboxypeptidase. However we can
      not rule out the possibility that it represents another carboxypeptidase not yet
      described.

PMID- 9144329
TI  - RAGE mRNA expression in the diabetic mouse kidney.
AB  - Receptors for advanced glycation end products (RAGE), which bind and internalize
      AGE-modified proteins formed from oxidation and other products of the
      nonenzymatic glycation reaction, have been mechanistically implicated in the
      development of the chronic complications of diabetes. In the present experiments,
      we sought evidence for the participation of RAGE in diabetic nephropathy by
      analysis of steady state levels of mRNA encoding RAGE in the renal cortex of a
      well-defined animal model (the db/db mouse) that develops renal pathology similar
      to that found in human diabetes. In these animals, increased AGE-product
      formation was confirmed by measurement of fluorescence in serum and renal cortex
      proteins. Renal involvement was confirmed by demonstration of increased urine
      albumin excretion and elevated serum creatinine concentrations relative to
      nondiabetic (db/m) littermate controls. Despite elevated concentrations of
      circulating and tissue AGE-modified proteins, the level of RAGE mRNA expression
      in renal cortex of diabetic mice did not significantly differ from that in
      nondiabetic littermate controls. The findings militate against changes in RAGE
      expression in the pathogenesis of renal abnormalities in this animal model.

PMID- 9144330
TI  - Ehrlich ascites tumor cells produce a transforming growth factor-beta (TGFbeta)
      like activity but lack receptors with TGFbeta-binding capacity.
AB  - Ehrlich ascites tumor cells incorporate [methyl-3H]thymidine into DNA
      independently of exogenous growth factors or fetal calf serum. Using an
      acid/ethanol extraction procedure we have obtained from these tumor cells a
      fraction that induces both the proliferation and the formation of cell foci by
      Swiss 3T3 mouse fibroblasts in the presence of insulin; inhibits the
      proliferation of Mv1Lu mink lung epithelial cells; and stimulates the growth of
      NRK rat kidney fibroblasts in soft-agar in the presence of epidermal growth
      factor. An antibody against transforming growth factor-beta (TGFbeta) prevents
      both the tumor extract-induced proliferation of Swiss 3T3 fibroblasts and the
      tumor extract-induced proliferative arrest of Mv1Lu cells. The tumor cells
      secrete a TGF beta-like activity to the extracellular medium in a partially
      activated form. However, authentic TGFbeta does not affect their proliferation,
      and no TGFbeta receptors were detected using [125I]TGFbeta as a ligand.
      Therefore, the absence of TGFbeta receptors with ligand-binding capacity in these
      tumor cells may bypass the negative control that this factor exerts on the
      proliferation of their normal cell counterparts.

PMID- 9144331
TI  - Differentiation of Y79 cells induced by prolonged exposure to insulin.
AB  - Y79 human retinoblastoma cells are known to contain receptors for both insulin
      and insulin-like growth factors (IGFs), to produce these cytokines and release
      them in the culture medium. Previously we have demonstrated that IGFs and insulin
      stimulate Y79 cell proliferation through the involvement of type I IGF receptor
      and Insulin Receptor Substrate 1 (IRS-1). This paper studies the effect of
      prolonged exposure to insulin on Y79 cells. Cells grown for 10 days in the
      presence of insulin were reseeded and incubated once more with insulin. In the
      reseeded cells proliferation lowered and morphological changes appeared. After 10
      days of reseeding, cells stopped proliferating and showed long ramifying neurite
      processes and varicosities consistent with neuronal differentiation.
      Morphological differentiation was accompanied by a marked increase in the content
      of total protein and in that of tubulin, the major protein constituent of
      microtubules, a marked increase in the content of specialized protein markers of
      dopaminergic and cholinergic differentiation (dopamine beta-hydroxylase and
      choline acetyltransferase activities, respectively); a contemporaneous decrease
      in the content of glial fibrillary acidic protein (GFAP), a specific marker of
      glial cells, was also observed. Our results demonstrate that prolonged exposure
      to insulin induces Y79 cells to differentiate into a neuronal-like phenotype. At
      this moment it is not possible to establish the mechanism by which insulin
      induces this differentiative effect.

PMID- 9144332
TI  - Angiotensin II stimulates rapid serine phosphorylation of transcription factor
      Stat3.
AB  - In rat neonatal cardiac fibroblasts and CHO-K1 cells expressing angiotensin type
      1 receptors, angiotensin II (AII) rapidly caused a time dependent reduction in
      the SDS-polyacrylamide gel electrophoretic mobility of Stat3 (Signal Transducer
      and Activator of Transcription). This was concentration dependent and detected at
      a low/physiological concentration of AII (1 nM), with initial effect observed as
      early as 2 min; and maximal at 5 min. The rapid stimulation of Stat3 mobility
      retardation by AII, paralleled the rapid activation of MAP kinases (mitogen
      activated protein kinases), and both were sensitive to the MAP kinase kinase 1
      inhibitor, PD98059. Immunoprecipitation of Stat3 from [32P] labeled cells
      demonstrated a 4-fold increase in Stat3 phosphorylation in response to AII, and
      phosphoamino acid analysis indicated that phosphorylation occurred on serine
      residues. Angiotensin II-induced rapid phosphorylation of Stat3 was also
      sensitive to the MAP kinase kinase 1 inhibitor, PD98059. Treatment of
      immunoprecipitated Stat3 from AII-treated cells with protein phosphatase- PP-2A,
      reversed the AII-induced retardation of Stat3 mobility. These results demonstrate
      that AII rapidly induces Stat3 serine phosphorylation through a MAP kinase kinase
      1 dependent pathway. Rapid stimulation of Stat3 serine phosphorylation by AII may
      have implications in the modulation of its transcriptional activity and gene
      expression.

PMID- 9144333
TI  - Antioxidant systems and anoxia tolerance in a freshwater turtle Trachemys scripta
      elegans.
AB  - The effects of anoxic submergence (20 h at 5 degrees C) and subsequent 24 h
      aerobic recovery on the antioxidant systems of six organs were examined in
      freshwater turtles, Trachemys scripta elegans. Both xanthine oxidase and xanthine
      dehydrogenase were detected in turtle tissues with xanthine oxidase composing 36
      75% of the total activity. Turtle organs displayed high constitutive activities
      of catalase (CAT), superoxide dismutase (SOD), and alkyl hydroperoxide reductase
      (AHR). Measurements of lipid peroxidation damage products (conjugated dienes,
      lipid hydroperoxides, thiobarbituric acid reactive substances) showed minimal
      changes during anoxia or recovery suggesting that natural anoxic-aerobic
      transitions occur without the free radical damage that is seen during ischemia
      reperfusion in mammals. Anoxia exposure led to selected decreases in enzyme
      activities in organs, consistent with a reduced potential for oxidative damage
      during anoxia: SOD decreased in liver by 30%, CAT decreased in heart by 31%, CAT
      and total glutathione peroxidase (GPOX) decreased in kidney (by 68 and 41%), and
      CAT and SOD decreased in brain (by 80 and 15%). AHR, however, increased 2 and 3.5
      fold during anoxia in heart and kidney respectively. Most anoxia-induced changes
      were reversed during aerobic recovery although brain enzyme activities remained
      suppressed. Some specific changes occurred during the recovery period: SOD
      increased from controls in heart by 45%, AHR increased to 200 and 168% of control
      values in red and white muscle respectively, and total GPOX decreased from
      controls in heart and white muscle by 75 and 77% respectively. The results show
      that biochemical adaptation for natural anoxia tolerance in turtles includes well
      developed antioxidant defenses that minimize or prevent damage by reactive oxygen
      species during the reoxygenation of organs after anoxic submergence.

PMID- 9144334
TI  - High D-glucose does not affect binding of alpha-tocopherol to human erythrocytes.
AB  - The role of alpha-tocopherol uptake system in human erythrocyte in the uptake of
      plasma alpha-tocopherol has been suggested. However no information is available
      on alpha-tocopherol uptake activity of human erythrocytes in the presence of high
      levels of D-glucose which is known to lead to pathological alterations in
      different cells including human erythrocytes. Therefore, in order to examine the
      effect of D-glucose on the binding of alpha-tocopherol to human erythrocytes, the
      binding characteristics of alpha-tocopherol to these cells were established
      first. Binding of [3H]alpha-tocopherol to human erythrocytes was both saturable
      and specific. Scatchard analysis of alpha-tocopherol binding to these cells
      showed the presence of two independent classes of binding sites with widely
      different affinities. The high affinity binding sites had a dissociation constant
      (Kd1) of 90 nM with a binding capacity (n1) of 900 sites per cell, whereas the
      low affinity binding sites had a dissociation constant (Kd2) of 5.2 microM and a
      binding capacity (n2) of 105,400 sites per cell. Trypsin treatment abolished all
      the alpha-tocopherol binding activity. Competition for the binding of alpha
      tocopherol to human erythrocytes was effective with other homologues of alpha
      tocopherol (beta-tocopherol, gamma-tocopherol and delta-tocopherol) and their
      potency was almost equal to alpha-tocopherol itself. The order of preference was
      alpha-tocopherol > beta-tocopherol > or = gamma-tocopherol > or = delta
      tocopherol. Incubation of human erythrocytes with various concentrations of D
      glucose did not affect alpha-tocopherol uptake activity. Our data demonstrate the
      presence of an alpha-tocopherol uptake system in human erythrocytes and that the
      alpha-tocopherol uptake activity is not modulated by the presence of D-glucose.

PMID- 9144336
TI  - Which bone density measurement?

PMID- 9144335
TI  - Comparisons of noninvasive bone mineral measurements in assessing age-related
      loss, fracture discrimination, and diagnostic classification.
AB  - The purpose of this study was to examine the commonly available methods of
      noninvasively assessing bone mineral status across three defined female
      populations to examine their interrelationships, compare their respective
      abilities to reflect age- and menopause-related bone loss, discriminate
      osteoporotic fractures, and classify patients diagnostically. A total of 47
      healthy premenopausal (age 33 +/- 7 years), 41 healthy postmenopausal (age 64 +/-
      9 years), and 36 osteoporotic postmenopausal (age 70 +/- 6 years) women were
      examined with the following techniques: (1) quantitative computed tomography of
      the L1-L4 lumbar spine for trabecular (QCT TRAB BMD) and integral (QCT INTG BMD)
      bone mineral density (BMD); (2) dual X-ray absorptiometry of the L1-L4 posterior
      anterior (DXA PA BMD) and L2-L4 lateral (DXA LAT BMD) lumbar spine, of the
      femoral neck (DXA NECK BMD) and trochanter (DXA TROC BMD), and of the ultradistal
      radius (DXA UD BMD) for integral BMD; (3) peripheral QCT of the distal radius for
      trabecular BMD (pQCT TRAB BMD) and cortical bone mineral content (BMC) (pQCT CORT
      BMC); (4) two radiographic absorptiometric techniques of the metacarpal (RA METC
      BMD) and phalanges (RA PHAL BMD) for integral BMD; and (5) two quantitative
      ultrasound devices (QUS) of the calcaneus for speed of sound (SOS CALC) and
      broadband ultrasound attenuation (BUA CALC). In general, correlations ranged from
      (r = 0.10-0.93) among different sites and techniques. We found that pQCT TRAB BMD
      correlated poorly (r < or = 0.46) with all other measurements except DXA UD BMD
      (r = 0.62,p < or = 0.0001) and RA PHAL BMD (r = 0.52, p < or = 0.0001). The
      strongest correlation across techniques was between QCT INT BMD and DXA LAT BMD
      (r = 0.87, p < or = 0.0001), and the weakest correlation within a technique was
      between pQCT TRAB BMD and pQCT CORT BMC (r = 0.25,p < or = 0.05). Techniques
      showing the highest correlations with age in the healthy groups also showed the
      greatest differences among groups. They also showed the best discrimination (as
      measured by the odds ratios) for the distinction between healthy postmenopausal
      and osteoporotic postmenopausal groups based on age-adjusted logistic regression
      analysis. For each anatomic site, the techniques providing the best results were:
      (1) spine, QCT TRAB BMD (annual loss, -1.2% [healthy premenopausal and healthy
      postmenopausal]); Student's t-value [not the T score], 5.4 [healthy
      postmenopausal vs. osteoporotic postmenopausal]; odds ratio, 43 [age-adjusted
      logistic regression for healthy postmenopausal vs. osteoporotic postmenopausal]);
      (2) hip, DXA TROC BMD (-0.46; 3.5; 2.2); (3) radius, DXA UD BMD (-0.44; 3.3; 1.9)
      and pQCT, CORT BMC (-0.72; 2.9; 1.7); (4) hand, RA PHAL (-0.51; 3.6; 2.0); and
      (5) calcaneus, SOS (-0.09; 3.4; 2.1) and BUA (-0.52; 2.6; 1.7). Despite these
      performance trends, the differences among sites and techniques were statistically
      insignificant (p > 0.05) using age-adjusted receiver operating characteristic
      (ROC) curve analysis. Nevertheless, kappa score analysis (using -2.0 T score as
      the cut-off value for osteopenia and -2.5 T score for osteoporosis) showed that
      in general the diagnostic agreement among these measurements in classifying women
      as osteopenic or osteoporotic was poor, with kappa scores averaging about 0.4
      (exceptions were QCT TRAB/INTG BMD, DXA LAT BMD, and RA PHAL BMD, with kappa
      scores ranging from 0.63 to 0.89). Often different patients were estimated at
      risk by using different measurement sites or techniques.

PMID- 9144337
TI  - The Ca2+-sensing receptor (CaR) activates phospholipases C, A2, and D in bovine
      parathyroid and CaR-transfected, human embryonic kidney (HEK293) cells.
AB  - The extracellular Ca2+ (Ca2+(o))-sensing receptor (CaR) is a G protein-coupled
      receptor that activates phospholipase C (PLC). In the present studies, we
      assessed Ca2+(o)-dependent changes in the generation of inositol phosphates (IP),
      free arachidonic acid (AA), and phosphatidylbutanol (PtdBtOH) by PLC,
      phospholipase A2 (PLA2), and phospholipase D (PLD), respectively, in bovine
      parathyroid cells as well as in wild-type or CaR-transfected human embryonic
      kidney (HEK293) cells (HEK-WT and HEK-CaR, respectively). Elevated Ca2+(o)
      increased the formation of IPs in parathyroid cells as well in HEK-CaR but not in
      HEK-WT cells. High Ca2+(o) also elicited time- and dose-dependent increases in
      PtdBtOH in parathyroid cells and HEK-CaR but not in HEK-WT cells. Brief treatment
      of parathyroid and HEK-CaR cells with an activator of protein kinase C (PKC),
      phorbol 12-myristate,13-acetate (PMA), stimulated PLD activity at both low and
      high Ca2+(o). Moreover, high Ca2+(o)-stimulated PLD activity was abolished
      following down-regulation of PKC by overnight phorbol myristate acetate (PMA)
      pretreatment, suggesting that CaR-mediated activation of PLD depends largely upon
      stimulation of PKC. High Ca2+(o) likewise increased the release of free AA in
      parathyroid and HEK-CaR but not in HEK-WT cells. Mepacrine, a general PLA2
      inhibitor, and AACOCF3, an inhibitor of cytosolic PLA2, reduced AA release in
      parathyroid cells at high Ca2+(o), suggesting a major role for PLA2 in high
      Ca2+(o)-elicited AA release. Pretreatment of parathyroid cells with PMA
      stimulated release of AA at low and high Ca2+(o), while a PKC inhibitor,
      chelerythrine, reduced AA release at high Ca2+(o) to the level observed with low
      Ca2+(o) alone. Thus, PKC contributes importantly to the high Ca2+(o)-evoked, CaR
      mediated activation of not only PLD but also PLA2. Finally, high Ca2+(o)
      stimulated production of IP, PtdBtOH, and AA all decreased substantially in
      parathyroid cells cultured for 4 days, in which expression of the CaR decreases
      by 80% or more, consistent with mediation of these effects by the receptor. Thus,
      the CaR activates, directly or indirectly, at least three phospholipases in
      bovine parathyroid and CaR-transfected HEK293 cells, providing for coordinate,
      receptor-mediated regulation of multiple signal transduction pathways in
      parathyroid and presumably other CaR-expressing cells.

PMID- 9144339
TI  - Dexamethasone stimulates osteoclast-like cell formation by directly acting on
      hemopoietic blast cells and enhances osteoclast-like cell formation stimulated by
      parathyroid hormone and prostaglandin E2.
AB  - Although an excess of glucocorticoid induces secondary osteoporosis, the
      mechanism still remains unclear, particularly in regard to glucocorticoid
      stimulated bone resorption. We examined the effects of dexamethasone (Dex) on
      osteoclast-like cell formation and bone-resorbing activity by employing mouse
      bone and spleen cell cultures and further investigated whether Dex would modulate
      osteoclast-like cell formation stimulated by several bone-resorbing factors. Dex
      stimulated osteoclast-like cell formation in stromal cell-containing mouse bone
      cell cultures in a concentration-dependent manner. Also, Dex significantly
      stimulated osteoclast-like cell formation from hemopoietic blast cells in spleen
      cell cultures derived from 5-fluorouracil-pretreated mice. In contrast, Dex (10(
      8) M) did not affect the bone-resorbing activity of mature osteoclasts.
      Pretreatment with 10(-8) M Dex significantly enhanced osteoclast-like cell
      formation in unfractionated mouse bone cell cultures stimulated by 10(-8) M human
      (h) parathyroid hormone (PTH) (1-34), 10(-8) M hPTH-related protein (1-34) and
      10(-6) M prostaglandin E2, but not by 10(-8) M 1,25-dihydroxyvitamin D3
      (1,25(OH)2D3). Moreover, pretreatment with 10(-8) M Dex significantly enhanced
      osteoclast-like cell formation stimulated by both forskolin and dbcAMP. In
      contrast, pretreatment with 10(-8) M Dex significantly inhibited osteoclast-like
      cell formation in mouse spleen cell cultures stimulated by both 10(-8) M hPTH(1
      34) and 10(-8) M 1,25(OH)2D3. These findings suggest that Dex stimulates
      osteoclast-like cell formation, at least in part by directly acting on
      hemopoietic blast cells. They further suggest that Dex enhances osteoclast-like
      cell formation stimulated by PTH and prostaglandin E2 through an indirect pathway
      via cells other than hemopoietic blast cells.

PMID- 9144338
TI  - Quantification of vitamin D receptor mRNA by competitive polymerase chain
      reaction in PBMC: lack of correspondence with common allelic variants.
AB  - It has been recently claimed that polymorphism for the vitamin D receptor (VDR)
      influences several aspects of calcium and bone metabolism. To evaluate the
      physiologic plausibility of these claims, we compared the abundance of the VDR
      mRNA in peripheral blood mononuclear cells (PBMCs) between different VDR
      genotypes using a quantitative reverse transcribed polymerase chain reaction
      based method. The method is based on the coamplification of VDR cDNA and an
      internal standard consisting of known concentrations of a human VDR CDNA mutated
      at a BglII restriction site; the interassay coefficient of variation is 11%. To
      validate the method, we made use of earlier receptor binding studies indicating
      that normal human monocytes and activated, but not resting, lymphocytes expressed
      the VDR. The concentration of the VDR mRNA was 10(-8) to 10(-7) g/g of total RNA
      in cell-sorted monocytes and in in vitro activated lymphocytes, but only 10(-12)
      g/g of total mRNA in resting lymphocytes, establishing that the VDR mRNA
      determined by our method in PBMCs is due to constitutive expression in monocytes.
      Following an initial genotype screening of 85 normal volunteers by polymerase
      chain reaction or restriction fragment length polymorphism analysis, 14
      individuals with the Bb genotype, 12 with the bb genotype, and 12 with the BB
      genotype were selected. The concentration of the VDR mRNA, corrected for the
      number of monocytes, was similar among the three genotype groups, as were the
      other variables examined: serum calcitriol, serum osteocalcin, and vertebral and
      hip bone density. We conclude that VDR polymorphism does not affect the abundance
      of the VDR mRNA.

PMID- 9144340
TI  - Evidence of a correlation of estrogen receptor level and avian osteoclast
      estrogen responsiveness.
AB  - Isolated osteoclasts from 5-week-old chickens respond to estradiol treatment in
      vitro with decreased resorption activity, increased nuclear proto-oncogene
      expression, and decreased lysosomal enzyme secretion. This study examines
      osteoclasts from embryonic chickens and egg-laying hens for evidence of estrogen
      responsiveness. Although osteoclasts from both of these sources express estrogen
      receptor mRNA and protein, estradiol treatment had no effect on resorption
      activity. In contrast to the lack of effect on resorption, estradiol treatment
      for 30 minutes resulted in steady-state mRNA levels of c-fos and c-jun increasing
      in osteoclasts from embryonic chickens and decreasing in osteoclasts from egg
      laying hens. These data suggest that a nuclear proto-oncogene response may not be
      involved in estradiol-mediated decreased osteoclast resorption activity. To
      examine the influence of circulating estrogen on osteoclast estrogen
      responsiveness, 5-week-old chickens were injected with estrogen for 4 days prior
      to sacrifice. Estradiol treatment of osteoclasts from these chickens did not
      decrease resorption activity in vitro. Transfection of an estrogen receptor
      expression vector into osteoclasts from the estradiol-injected chickens and egg
      laying hens restored estrogen responsiveness. Osteoclasts from 5-week-old
      chickens and estradiol treated 5-week-old chickens transfected with the estrogen
      receptor expression vector contained significantly higher levels of estrogen
      receptor protein and responded to estradiol treatment by decreasing secretion of
      cathepsins B and L and tartrate-resistant acid phosphatase. In contrast,
      osteoclasts from embryonic chickens, egg-laying hens, and estradiol-treated 5
      week-old chickens either untransfected or transfected with an empty expression
      vector did not respond similarly. These data suggest that modulation of
      osteoclast estrogen responsiveness may be controlled by changes in the osteoclast
      estrogen receptor levels.

PMID- 9144341
TI  - Characterization and cellular distribution of the osteoclast ruffled membrane
      vacuolar H+-ATPase B-subunit using isoform-specific antibodies.
AB  - Acidification of the bone surface, leading to bone resorption, is accomplished by
      a vacuolar-type H+-ATPase present in a specialized domain of the plasma membrane
      of the osteoclast known as the ruffled membrane. Structure and function appears
      to be highly conserved within this class of multisubunit enzymes. However,
      cloning and sequencing of complementary DNA has shown that one of the subunits in
      the catalytic domain, the B-subunit, exists in at least two forms, B1 and B2. B1
      messenger RNA has been found almost exclusively in the kidney, whereas messenger
      RNA for B2 has been found in all tissues studied, including the kidney. It has
      been speculated that the B1 isoform might be involved in targeting to the plasma
      membrane. In the present study, we have characterized the B-subunit of the
      chicken osteoclast H+-ATPase using antibodies directed against peptides with
      isoform-specific or conserved sequences of the B-subunit. Western analysis was
      performed on chicken osteoclast membrane vesicles and on partially purified
      chicken osteoclast H+-ATPase and was compared with similar analysis of H+-ATPase
      isolated from bovine kidney and brain. The B1-specific antibody reacted with a
      polypeptide of approximately 56 kD on immunoblots of the renal H+-ATPase, whereas
      no reaction could be detected against the osteoclast H+-ATPase or the osteoclast
      membrane vesicle preparation. In contrast, the antibody against a B2-specific
      sequence reacted with a peptide of approximately 56 kD on immunoblots of the
      osteoclast H+-ATPase, the renal H+-ATPase, and the clathrin-coated vesicle H+
      ATPase. The antibody against a conserved region of the B-subunit did not generate
      any evidence for the presence of isoforms other than B2 in the osteoclast.
      Immunocytochemistry of rat osteoclasts on bovine bone slices using the B2
      antibody showed intense polarized staining along the plasma membrane facing the
      bone surface in actively resorbing osteoclasts whereas nonresorbing osteoclasts
      were diffusely stained throughout the cytoplasm. By confocal microscopy, the B2
      staining was located to the level of the ruffled membrane and appeared to be
      concentrated to the peripheral areas of the membrane adjacent to the sealing
      zone. We conclude that the osteoclast vacuolar H+-ATPase contains the B2 isoform
      and suggest that upon initiation of resorption the pump is translocated from the
      cell interior to a special domain of the ruffled membrane close to the sealing
      zone.

PMID- 9144342
TI  - Plasminogen activator system in osteoclasts.
AB  - To determine which genes of the plasminogen activator (PA) system were expressed
      in osteoclasts, RNA extracted from microisolated mouse osteoclasts was used as
      template for reverse transcribed polymerase chain reaction (RT-PCR) with gene
      specific primer pairs. Using this approach, the expression of RNAs for tissue
      type plasminogen activator, urokinase-type plasminogen activator, plasminogen
      activator inhibitor-1, plasminogen activator inhibitor-2, protease nexin, and
      urokinase receptor isoform 1 (uPAR1) were detected in mouse osteoclasts. The
      expression of uPAR RNA in osteoclasts was confirmed by in situ hybridization with
      a uPAR1 probe. RNA encoding the uPAR isoform 2 was not detected in mouse
      osteoclasts, but a novel unspliced uPAR RNA variant was detected in these cells.
      The novel uPAR variant and uPAR1 RNA were also detected in mouse calvarial
      osteoblasts, kidney, muscle, and the mouse macrophage cell line J774A.1 by RT
      PCR. The presence of RNAs for most of the components of the PA system in
      osteoclasts suggests that it may have a functional role in this cell type.

PMID- 9144343
TI  - Early responses to dynamic strain change and prostaglandins in bone-derived cells
      in culture.
AB  - Mechanical loading of bone explants stimulates prostaglandin E2 (PGE2) and
      prostacyclin (PGI2) release and increases glucose 6-phosphate dehydrogenase
      (G6PD) activity. This response is blocked by indomethacin and imitated by
      exogenous PGs. In the experiments reported here, primary cultures of rat long
      bone-derived osteoblast-like cells were exposed to a dynamic strain and exogenous
      PGs in the culture dish. Strain (3400 mu epsilon, 600 cycles, 1 Hz) caused an
      immediate release of PGI2 into the culture medium but had no effect on PGE2.
      Strain also caused an increase in G6PD activity per cell and an increase in the
      smallest transcript of insulin-like growth factor II (IGF-II) (IGF-II T3) but had
      no effect on the expression of transforming growth factor-beta1 (TGF-beta1).
      Indomethacin inhibited strain-induced release of PGI2 and suppressed strain
      induced stimulation of IGF-II T3 transcript. PGI2 (1 microM) increased G6PD
      activity and mRNA levels of all three transcripts of IGF-II but had no effect on
      the mRNA levels of IGF-I or TGF-beta1. PGE2 (1 microM) stimulated G6PD activity
      and caused a marked increase in IGF-I and the largest transcript of IGF-II (IGF
      II T1) but had no effect on the IGF-II transcripts T2 and T3 or on TGF-beta1 mRNA
      levels. These findings show similarities in response between osteoblast-like
      cells strained in monolayer culture and bone cells in loaded bone explants in
      situ. They provide support for a role for IGF-II and PGI2 in the early strain
      related response of osteoblasts in loading-related bone modeling/remodeling.

PMID- 9144344
TI  - C-terminal parathyroid hormone-related protein inhibits proliferation and
      differentiation of human osteoblast-like cells.
AB  - Parathyroid hormone-related protein (PTHrP) is synthesized by osteoblasts,
      although its local role in bone is not completely understood. The C-terminal (107
      111) region of PTHrP seems to be a potent inhibitor of osteoblastic bone
      resorption. We studied the effect of this PTHrP domain on the proliferation and
      synthesis of osteoblastic markers in osteoblast-like cells from adult human bone.
      We found that the human (h)PTHrP(107-139) fragment, between 10 fM and 10 nM,
      inhibited 3H-thymidine incorporation into these cells. The antiproliferative
      effect of the latter fragment, or that of hPTHrP(107-111), was similar to that
      induced by [Tyr34] hPTHrP(1-34) amide, bovine PTH(1-34), and hPTHrP(1-141), while
      hPTHrP(38-64) amide was ineffective. Human PTHrP(7-34) amide, at 10 nM, and 1
      microM phorbol-12-myristate-13-acetate also significantly decreased DNA synthesis
      in human osteoblast-like cells. Neither hPTHrP(7-34) amide nor hPTHrP(107-139),
      at 10 nM, stimulated protein kinase A (PKA) activity in these cells. Moreover,
      100 nM H-89, a PKA inhibitor, did not eliminate the inhibitory effect of
      hPTHrP(107-139) on these cells' growth. However 100 nM calphostin C, a PKC
      inhibitor, blunted this effect of PTHrP(107-139). In addition to their
      antimitogenic effect, hPTHrP(107-139) and hPTHrP(107-111) inhibited basal and
      1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-stimulated alkaline phosphatase activity
      in these cells. Both fragments, like 1,25(OH)2D3, decreased C-terminal type I
      procollagen secretion into the cell-conditioned medium, but osteocalcin secretion
      by these cells was unaffected by the C-terminal PTHrP fragments. These findings
      suggest that PTHrP may act as a local regulator of bone formation.

PMID- 9144345
TI  - Microgravity reduces the differentiation of human osteoblastic MG-63 cells.
AB  - Spaceflight leads to osteopenia in both humans and animals, principally as a
      result of decreased bone formation, which might be the consequence of impaired
      osteoblast differentiation. The effect of microgravity on osteoblast
      differentiation in vitro was investigated using the human osteosarcoma cell line
      MG-63. Genes related to matrix formation and maturation were quantified both at
      the protein and mRNA level in untreated and hormone-treated (dihydroxyvitamin D3
      [1,25(OH)2D3], 10(-7) M; transforming growth factor beta2 (TGF-beta2), 10 ng/ml)
      cells cultured for 9 days under microgravity conditions aboard the Foton 10
      satellite and compared with ground and inflight unit-gravity cultures. The
      expression of alkaline phosphatase (ALP) activity following treatment at
      microgravity increased only by a factor of 1.8 compared with the 3.8-fold
      increase at unit-gravity (p < 0.01), whereas no alteration was detected in the
      production of collagen type I between unit- and microgravity. In addition, gene
      expression for collagen Ialpha1, ALP, and osteocalcin following treatment at
      microgravity was reduced to 51, 62, and 19%, respectively, of unit-gravity levels
      (p < 0.02). The lack of correlation between collagen type I gene and protein
      expression induced by microgravity is most likely related to the different
      kinetics of gene and protein expression observed at unit-gravity: following
      treatment with 1,25(OH)2D3 and TGF-beta2, collagen Ialpha1 mRNA increased
      gradually during 72 h, but collagen type I production was already maximal after
      treatment for 48 h. In conclusion, microgravity decreases the activity of
      osteoblasts in vitro; in particular the differentiation of osteoblasts in
      response to systemic hormones and growth factors is reduced by microgravity.

PMID- 9144346
TI  - New aspects of endochondral ossification in the chick: chondrocyte apoptosis,
      bone formation by former chondrocytes, and acid phosphatase activity in the
      endochondral bone matrix.
AB  - A detailed histological study of the growth plates from 9- to 20-day-old
      embryonic chick long bones was carried out with the aim of clarifying the long
      debated question of the fate of the hypertrophic chondrocytes. Since resorption
      in chick bones does not occur synchronously across the plate as it does in
      mammals, specialized regions develop and the fate of the chondrocyte depends on
      its location within the growth plate. Where resorption took place, as at the
      sites of primary vascular invasion or at the main cartilage/marrow interface,
      chondrocytes underwent apoptosis before the lacunae were opened. In addition,
      spontaneous apoptosis of chondrocytes occurred at apparently random sites
      throughout all stages of chondrocyte differentiation. In older chick bones, a
      thick layer of endochondral bone matrix covered the cartilage edge. This
      consisted of type I collagen and the typical noncollagenous bone proteins but, in
      addition, contained tartrate-resistant acid phosphatase in the mineralized
      matrix. Where such matrix temporarily protected the subjacent cartilage from
      resorption, chondrocytes differentiated to bone-forming cells and deposited bone
      matrix inside their lacunae. At sites of first endochondral bone formation, some
      chondrocytes underwent an asymmetric cell division resulting in one daughter cell
      which underwent apoptosis, while the other cell remained viable and re-entered
      the cell cycle. This provided further support for the notion that chondrocytes as
      well as marrow stromal cells give rise to endochondral osteoblasts.

PMID- 9144347
TI  - Prevention of postmenopausal bone loss using tibolone or conventional peroral or
      transdermal hormone replacement therapy with 17beta-estradiol and dydrogesterone.
AB  - Postmenopausal bone loss can be prevented by continuous or intermittent estradiol
      (E2) administration. Concomitant progestogen therapy is mandatory in
      nonhysterectomized women to curtail the risk of endometrial hyperplasia or
      cancer. However, the recurrence of vaginal bleeding induced by sequential
      progestogen therapy in addition to continuous estrogen administration is one of
      the reasons for noncompliance to hormone replacement therapy (HRT). Tibolone, a
      synthetic steroid with simultaneous weak estrogenic, androgenic, and
      progestational activity, which does not stimulate endometrial proliferation, has
      recently been proposed for the treatment of climacteric symptoms. To compare the
      efficacy of conventional oral and transdermal HRT with that of tibolone in the
      prevention of postmenopausal bone loss, 140 postmenopausal women (age, 52 +/- 0.6
      years; median duration of menopause, 3 years) were enrolled in an open 2-year
      study. Volunteers had been offered a choice between HRT and no therapy (control
      group, CO). Patients selecting HRT were randomly allocated to one of the
      following three treatment groups: TIB, tibolone, 2.5 mg/day continuously, orally;
      PO, peroral E2, 2 mg/day continuously, plus sequential oral dydrogesterone (DYD),
      10 mg/day, for 14 days of a 28-day cycle; TTS, transdermal E2 by patch releasing
      50 microg/day, plus DYD as above. Bone densitometry of the lumbar spine, upper
      femur, and whole body was performed using dual-energy X-ray absorptiometry at
      baseline, and then 6, 12, 18, and 24 months after initiation of therapy. One
      hundred and fifteen women (82%) completed the 2 years of the study. The dropout
      rate was similar in each group. Over 2 years, bone preservation was observed in
      all three treatment groups as compared with controls, without significant
      differences among treatment regimens. In conclusion, tibolone can be regarded as
      an alternative to conventional HRT to prevent postmenopausal bone loss.

PMID- 9144348
TI  - Influence of physical activity on vertebral deformity in men and women: results
      from the European Vertebral Osteoporosis Study.
AB  - Physical activity is associated with an increased bone mass and a reduced risk of
      hip fracture. There are, however, no data from population samples of men and
      women concerning the effect of regular levels of physical activity on the risk of
      vertebral deformity. The aim of this study was to determine the relationship
      between regular physical activity and vertebral deformity in European men and
      women. A population survey method was used. Thirty-six centers from 19 European
      countries participated. Each center recruited a population sample of men and
      women aged 50 years and over. Those who took part received an interviewer
      administered questionnaire and lateral thoracolumbar radiographs. Subjects were
      asked about two dimensions of physical activity: (1) the level of physical
      activity undertaken either at work or at home on a daily basis at three different
      age periods: 15-25 years, 25-50 years, and 50+ years; and (2) the amount of time
      spent walking or cycling out of doors each day. Spinal radiographs were evaluated
      morphometrically and the presence of vertebral deformity was defined according to
      the McCloskey method. In total, 14,261 subjects, aged 50-79 years, from 30
      centers were studied, of whom 809 (12.0%) men and 884 (11.7%) women had one or
      more deformities. After adjusting for age, center, smoking, and body mass index,
      very heavy levels of activity in all three age groups were associated with an
      increased risk of vertebral deformity in men (odds ratios, age adjusted [OR], 1.5
      1.7; with all 95% confidence intervals [CI] excluding unity). No increased risk
      was observed in women. Current walking or cycling more than 1/2 h/day was
      associated with a reduced risk of vertebral deformity in women (OR 0.8; 95% CI
      0.7-1.0). We conclude that regular walking in middle-aged and elderly women is
      associated with a reduced risk of vertebral deformity. By contrast, heavy levels
      of physical activity in early and middle adult life are associated with an
      increased risk in men. These differences are of relevance in understanding the
      epidemiology of vertebral deformity and planning programs of prevention.

PMID- 9144349
TI  - Long-term changes in bone mineral and biomechanical properties of vertebrae and
      femur in aging, dietary calcium restricted, and/or estrogen-deprived/-replaced
      rats.
AB  - To study the long-term effect of aging, low calcium diet (LCD) and/or ovariectomy
      (OVX), and estrogen replacement therapy (+E) on rat bone quality of both
      trabecular and cortical bone, 150 female Wistar rats of 4.5 months were divided
      into baseline, sham-operation (sham), sham + LCD, OVX, OVX + E, OVX + LCD, OVX +
      LCD + E, and were observed for 3, 6, and 9 months postsurgery. The bone mineral
      density (BMD) of the lumbar spine L1-L4, the femoral neck, the midshaft, and the
      distal metaphysis were determined using dual-energy X-ray absorptiometry (DXA) in
      vitro. Biomechanical tests of the L1 vertebral body and the left femur were
      performed. The right femoral midshaft and neck were processed undecalcified for
      determining cross-sectional moments of inertia (CSMIs). BMD in all groups
      increased rapidly with aging in the femoral midshaft composed only of cortical
      bone at 3 months post-OVX and stabilized or decreased thereafter, but decreased
      at all observation periods in the distal femoral metaphysis, consisting mostly of
      trabecular bone. L1 maximum compressive strength and stiffness increased as a
      function of aging in sham and sham + LCD but not in OVX and OVX + LCD. The order
      of loss in BMD at all sites and in L1 strength and stiffness was: OVX + LCD > OVX
      > LCD. LCD reduced while OVX improved the total femoral area, CSMIs in the
      femoral midshaft, and the torsional strength. Estrogen treatment preserved BMD
      and prevented OVX-induced loss in L1 strength. The BMD and biomechanical
      properties were greater in OVX + E than in OVX + LCD + E. Loss in BMD and CSMIs
      was greater in the femoral neck than in the midshaft. The data suggest that rat
      cortical bone might not be matured until 7.5 months of age. It would be more
      appropriate to consider rats at peak bone mass as a model of mature rat and to
      perform OVX at that time. LCD and OVX have a great potential for weakening the
      bone quality of cortical bone and trabecular bone, respectively, and have an
      additive effect when combined. Estrogen prevents only OVX-induced bone loss.

PMID- 9144351
TI  - Quantitative ultrasound of the calcaneus reflects the mechanical properties of
      calcaneal trabecular bone.
AB  - To provide new information about the potential role of quantitative ultrasound
      (QUS) in fracture risk prediction, we assessed whether QUS and densitometric
      variables derived from measurements of intact cadaveric feet were associated with
      the mechanical properties of calcaneal trabecular bone. We obtained 31 intact
      cadaveric feet from the local anatomic gifts program, including 13 men and 18
      women, with a mean age of 77 years (range 50-91 years). Broadband ultrasound
      attenuation (BUA) and ultrasound transit velocity (SOS) were assessed in the
      intact cadaveric feet using a water-based ultrasound system. In addition, we
      measured the bone mineral density (BMD) of the posterior calcaneus using dual
      energy X-ray absorptiometry. Cubes of trabecular bone were then removed from the
      calcaneus at approximately the same location as the QUS measurements were
      obtained, and the elastic modulus and ultimate strength of the trabecular bone
      specimens were measured by compressing them in the mediolateral direction. We
      found that QUS variables were moderately to strongly correlated with the
      mechanical properties of calcaneal trabecular bone (r2 = 0.48-0.63, p < 0.001 for
      all). However, the strongest associations with the mechanical properties
      trabecular bone were provided by calcaneus BMD and trabecular bone apparent
      density (r2 = 0.66-0.88). BUA and densitometric measurements were independently
      associated with elastic modulus, but not with ultimate strength. Our results
      indicate that QUS measurements of the intact heel are associated with the
      mechanical properties of calcaneal trabecular bone and, in some cases, provide
      information in addition to that provided by BMD or density measurements.

PMID- 9144350
TI  - A new trabecular region of interest for femoral dual X-ray absorptiometry: short
      term precision, age-related bone loss, and fracture discrimination compared with
      current femoral regions of interest.
AB  - We defined a new region of interest (ROI) for femoral Ward's triangle, centered
      on the femoral neck axis including comparatively trabecular-rich bone. Forty
      seven premenopausal, 39 healthy postmenopausal, and 35 osteoporotic
      postmenopausal women with vertebral fractures were evaluated comparing the new
      with the standard femoral ROIs, using a Hologic QDR-2000. Additionally, spinal
      dual X-ray absorptiometry (DXA) was performed. The short-term precision error of
      the new ROI expressed as the root mean square of the coefficient of variations
      was 1.34% for premenopausal women, 1.69% for healthy postmenopausal women, and
      2.46% for osteoporotic postmenopausal women. Bone mineral density (BMD) values of
      the new ROI correlated highly with those of the standard femoral ROIs (r = 0.91 -
      0.96) and the spinal BMD (r = 0.74). Age-related bone loss of the new ROI was
      0.75% per year (r = 0.66) in healthy women, which was approximately 1.5 times
      higher than the bone loss of the standard femoral ROIs, except for Ward's
      triangle. Regarding the intergroup discrimination, the t-value of the new ROI was
      similar to the t-value of Ward's triangle, and the intergroup percent decrements
      in BMD of the new ROI approximated those of Ward's triangle. For discriminating
      women with vertebral fractures, the new ROI demonstrated odds ratios of 1.6
      similar to most ROIs but lower than that of the trochanteric region. The new,
      substantially trabecular ROI appears to be an alternative to the Ward's ROI
      traditionally used in femoral DXA having improved short-term precision and
      comparable sensitivity.

PMID- 9144352
TI  - Synovial fluids from patients with osteoarthritis and rheumatoid arthritis
      contain high levels of parathyroid hormone-related peptide.
AB  - High levels of immunoreactive and biologically active parathyroid hormone-related
      peptide (PTHrP) were detected in synovial fluids from patients with
      osteoarthritis (OA) and rheumatoid arthritis (RA). The levels of PTHrP
      immunoreactivity in synovial fluids, measured by a two-site immunoradiometric
      assay (IRMA) which detects hPTHrP(1-72) or longer peptides and a radioimmunoassay
      (RIA) specific to the carboxy-terminal portion of hPTHrP, were 3.2 +/- 0.3 pmol
      of hPTHrP(1-86)/l and 61 +/- 7.0 pmol of hPTHrP(109-141)/l in OA patients (mean
      +/- SE, n = 23), and 4.8 +/- 0.8 pmol of hPTHrP(1-86)/l and 164 +/- 30 pmol of
      hPTHrP(109-141)/l in RA patients (n = 26). Synovial fluid PTHrP levels
      distributed above the normal plasma reference ranges in each assay (0.7-2.6 pmol
      of hPTHrP(1-86)/l; 16-60.6 pmol of hPTHrP(109-141)/l). After concentration using
      sequential cation-exchange and reverse-phase chromatography, synovial fluid
      exhibited the activity that stimulated cyclic adenosine monophosphate (cAMP)
      accumulation in osteoblastic ROS 17/2.8 cells expressing PTH/PTHrP receptors. The
      cAMP accumulation activity in synovial fluid was sensitive to coincubation with
      excess hPTHrP(3-40), a PTH/PTHrP receptor antagonist, and was completely
      neutralized by preincubation with a monoclonal antibody specific to hPTHrP but
      not PTH. Immunohistochemical analysis of RA synovium revealed that PTHrP was
      localized in fibroblast-like cells in the synovial pannus invading articular
      cartilage. Our data show that PTHrP is produced locally by the diseased synovial
      tissue and released into synovial fluid at high concentrations, allowing us to
      hypothesize that PTHrP plays a novel role as a paracrine/autocrine factor in the
      pathology of OA and RA.

PMID- 9144353
TI  - Fibrodysplasia ossificans progressiva (FOP).

PMID- 9144354
TI  - Primary hyperparathyroidism: still evolving?

PMID- 9144355
TI  - Does Paget's disease really have a viral aetiology?

PMID- 9144356
TI  - Clinical use of the measurement of soluble cell adhesion molecules in patients
      with autoimmune rheumatic diseases.

PMID- 9144357
TI  - Value of detecting immunoglobulin E antibodies for the serological diagnosis of
      Toxoplasma gondii infection.
AB  - The presence of immunoglobulin E (IgE) antibodies was determined by using the
      immunosorbent-agglutination assay (ISAGA) with 611 serum samples from patients
      with different clinical conditions to evaluate its value for the serodiagnosis of
      acute Toxoplasma gondii infection. By analyzing 43 consecutively drawn serum
      samples from 10 pregnant women who seroconverted, we could show that specific IgE
      antibodies seem to appear early after infection and are usually present for less
      than 3 to 5 months. Therefore, we assumed that IgE antibodies seem to be
      detectable only during the acute or reactivated stage of infection. According to
      our studies, the IgE ISAGA has an overall sensitivity of only 79.5%, but a
      specificity of 98.0%, with positive and negative predictive values of 95.5 and
      89.8%, respectively. Detection of IgE antibodies in immunosuppressed patients
      with reactivation of latent T. gondii infection correlates with disease activity.
      Despite these encouraging results, one must note that IgE antibodies were not
      detectable in 4 of 14 patients with very recent infection proven by
      seroconversion. Therefore, detection of IgE antibodies seems to correlate with
      early acute or reactivated toxoplasmosis, whereas negative IgE results do not
      exclude the possibility of the acute stage of toxoplasmosis.

PMID- 9144358
TI  - Detection of HLA class I-specific antibodies by the QuikScreen enzyme-linked
      immunosorbent assay.
AB  - The GTI QuikScreen test is an enzyme-linked immunosorbent assay (ELISA) that uses
      soluble HLA class I antigens as targets. In tests of 5,893 human serum specimens,
      we evaluated the reliability, sensitivity, and utility of the GTI QuikScreen test
      for detecting HLA class I-specific antibody. We found that the test could
      reliably detect HLA-specific antibodies of the immunoglobulin G (IgG) but not the
      IgM class. The degree of correlation with lymphocytotoxicity testing varied among
      the different serum sources, with the best correlation achieved with sera from
      renal transplant candidates (r > 0.7) and the poorest with sera from patients
      with end-stage liver disease (r = 0.26), possibly because of elevated alkaline
      phosphatase levels in the liver patients. Test reproducibility was high (96%),
      and test failure rate was low (1.7%). The test sensitivity is comparable to that
      of the antiglobulin cytotoxicity and, possibly, even flow cytometric tests. There
      was a highly significant (P < 0.001) correlation between the optical densities
      obtained in the ELISA and the percent panel reactive antibody determined by
      cytotoxicity testing. Therefore, although designed only to determine the presence
      or absence of HLA-specific antibody, GTI QuikScreen test results also provided an
      indication of the extent of sensitization. The test is one of the most effective
      and efficient ways to determine if antibodies producing a positive result in
      crossmatch tests are specific for HLA class I antigens. As an adjunct to serum
      screening by cytotoxicity testing, the GTI QuikScreen test can produce a
      substantial savings of time and effort that reduces the cost to the laboratory
      and to the patient.

PMID- 9144359
TI  - Increased frequency of HLA-DR11 in pediatric human immunodeficiency virus
      associated parotid gland enlargement.
AB  - We sought to determine whether an increased frequency of the HLA-DR11 (formerly
      DR5) phenotype is found in human immunodeficiency virus (HIV)-infected children
      with parotid gland enlargement. In HIV-infected adults, parotid gland enlargement
      may be part of the diffuse infiltrative CD8 lymphocytosis syndrome. An increased
      frequency of expression of HLA-DR11 has been described in association with
      diffuse infiltrative CD8 lymphocytosis syndrome. We conducted a case-control
      study with 26 HIV-infected children, 13 of whom had parotid gland enlargement and
      13 of whom did not but who were matched for age, race, and sex with those with
      parotid gland enlargement. Clinical and laboratory parameters (including HLA-DR11
      phenotype) were compared between the two groups. HIV-positive children with
      parotid gland enlargement showed an increased frequency of HLA-DR11, similar to
      their adult counterparts with diffuse infiltrative CD8 lymphocytosis syndrome.
      The HLA-DR11 phenotype may be associated with the development of parotid gland
      enlargement in HIV-infected children and may be a marker for a more benign
      outcome of HIV infection.

PMID- 9144360
TI  - Diagnosis of human immunodeficiency virus infection using citrated whole blood.
AB  - Standard isolation of human immunodeficiency virus type 1 (HIV-1) from peripheral
      blood mononuclear cells (PBMC) requires 5 to 20 ml of blood, and the centrifugal
      separation of PBMC is expensive and time-consuming. Whole-blood coculture
      techniques use small sample volumes, do not require centrifugation, and allow
      measurement of the total viral burden in peripheral circulation. We compared the
      results of citrated whole-blood coculture with those obtained by the standard
      AIDS Clinical Trials Group PBMC semiquantitative culture method and reverse
      transcription-PCR quantitation of plasma HIV-1 RNA levels. PBMC cocultures were
      also set up with added erythrocytes (RBCs) to determine if the presence of RBCs
      affects the replication of HIV-1 in vitro. The mean number of cells required for
      a p24-positive PBMC coculture was approximately seven times greater than that
      required for a positive citrated whole-blood coculture (P < 0.01). At volumes of
      100, 50, and 25 microl, the sensitivities of the whole-blood coculture were 94.5,
      93.6, and 87.3%, respectively. The PBMC culture in the presence of added RBCs was
      more sensitive than PBMC coculture alone. The citrated whole-blood coculture was
      simple to perform, produced a reliable diagnosis of HIV infection in adult
      volunteers, was more sensitive than previously reported techniques even in half
      the culture time, and showed less variability than the PBMC coculture. Citrated
      whole-blood coculture may be a useful and efficient tool for diagnosing infection
      with HIV-1.

PMID- 9144361
TI  - Vibriocidal antibody responses in North American volunteers exposed to wild-type
      or vaccine Vibrio cholerae O139: specificity and relevance to immunity.
AB  - The emergence of a new agent of cholera, Vibrio cholerae O139, has prompted a
      reevaluation of the vibriocidal antibody assay. This assay, primarily directed to
      lipopolysaccharide, is an important correlate of O1 immunity. V. cholerae O139
      strains are encapsulated, rendering them relatively resistant to killing by
      serum. Recent reports suggest that there is strain-to-strain variability in the
      sensitivity of the vibriocidal assay to fully encapsulated O139 strains. We have
      assessed a modified vibriocidal assay for fully encapsulated O139 strain AI-1837
      and its unencapsulated mutant 2L in sera from 53 volunteers given wild-type AI
      1837 or its attenuated derivative CVD 112 and from 48 controls challenged with V.
      cholerae O1 or strains of the family Enterobacteriaceae. Vibriocidal responses to
      the AI-1837 and 2L strains were seen in 67 and 89% of volunteers, respectively,
      following a single exposure to the wild-type strain. However, >50% of all
      controls had low-level vibriocidal responses to both strains. These nonspecific
      responses were transient and of the immunoglobulin G isotype. No binding activity
      against purified O139 lipopolysaccharide (LPS) by immunoblotting was seen in
      control sera. In contrast, vibriocidal assay and strain 2L LPS responses by
      immunoblotting were detectable in 91% of tested volunteers following a single
      exposure to O139. The presence of vibriocidal antibody to AI-1837 or 2L was not
      associated with protection in rechallenge studies with O139 strain AI-1837. The
      vibriocidal assay with unencapsulated strain 2L may be used to detect exposure to
      O139 strain AI-1837 in controlled research trials. However, its lack of
      specificity does not make it useful for determining exposure to V. cholerae O139
      in the field.

PMID- 9144362
TI  - Serological response over time to recombinant Neospora caninum antigens in cattle
      after a neosporosis-induced abortion.
AB  - Recombinant Neospora caninum tachyzoite antigens were evaluated in an enzyme
      linked immunosorbent assay (ELISA) for recognition by serum antibodies (Ab) from
      Neospora-infected cattle. Serum samples were obtained every 2 to 3 weeks for 8 to
      15 months from 10 cows with histories of Neospora-associated abortion. Serum
      samples were also obtained from offspring of these animals and from a large
      number of cows that had aborted a fetus, due to infection by Neospora or other
      organisms, at various times during gestation. All 10 cows had positive ELISA Ab
      titers to both recombinant N. caninum tachyzoite antigens after abortion, during
      subsequent gestation, and after parturition. In three cows, there was a
      noticeable peak in Ab titers early in gestation. Calves born to Neospora-infected
      cows also had positive titers of Ab to the recombinant tachyzoite antigens, and
      these titers remained elevated for at least 4 months after birth. A portion of
      the serum immunoglobulin in calves may have been derived from colostrum of
      infected cows. A calf born from a seronegative mother had a positive ELISA titer
      only after being fed colostrum from a seropositive cow. However, precolostral
      titers in calves born from Neospora-infected cows were high at birth, suggesting
      that the parasite was transmitted to the fetus via the placenta and induced a
      humoral immune response therein. The recombinant tachyzoite antigens were also
      useful for corroborating clinical diagnoses of Neospora-induced abortion. A
      significant difference (P < 0.05) between anti-recombinant antigen Ab titers in
      cows that aborted due to Neospora and those in cows that aborted from other
      causes was found.

PMID- 9144363
TI  - Heterogeneity of cell-associated CP5 expression on Staphylococcus aureus strains
      demonstrated by flow cytometry.
AB  - It was reported previously that two capsular polysaccharides, types 5 and 8 (CP5
      and CP8), account for 70 to 80% of Staphylococcus aureus strains isolated from
      human and animal sources. The capsular material has been shown to play a part in
      virulence and in resistance to phagocytosis. With a view to investigating the
      role that CP plays in pathogenicity or protection, relative measurement of cell
      associated CP is desirable. Flow cytometry, which permits the analysis of
      individual bacteria, was used to that end. Thirty isolates expressing CP5, of
      human (n = 7) and animal (cow, n = 11; goat, n = 3; swine, n = 3; hen, n = 3; and
      rabbit, n = 3) origin, were cultivated on either brain heart infusion agar (BHI)
      or modified medium 110 (mod 110) agar. Staphylococci were incubated with a mouse
      anti-CP5 monoclonal antibody (an immunoglobulin M, which does not react with
      staphylococcal protein A) and then stained with a fluorescein-labeled anti-murine
      antibody. The bacteria were washed, sonicated, and analyzed by flow cytometry.
      Except for three isolates, the expression of cell-bound CP5 was higher when
      bacteria were cultivated on mod 110 than when they were cultivated on BHI. We
      found a wide intraisolate phenotypic heterogeneity in surface-exposed CP5 in many
      strains, which appeared as mixtures of stained and unstained bacteria. Four main
      patterns could be distinguished on the basis of the distribution of the
      fluorescence of individual bacteria within the strain population as a function of
      growth medium. Great variations in both percentages of stained bacteria and
      fluorescence intensity were recorded among strains regardless of their origin.
      Flow cytometry analysis provided information on both the relative amounts and the
      distribution patterns of the surface expression of CP. This information is
      potentially useful for the evaluation of the part played by the capsule in the
      interaction of bacteria with host cells or for the study of the activities of
      antibodies to this target antigen, such as opsonization or prevention of
      adherence.

PMID- 9144364
TI  - Antibody and delayed-type hypersensitivity responses to Ochrobactrum anthropi
      cytosolic and outer membrane antigens in infections by smooth and rough Brucella
      spp.
AB  - Immunological cross-reactions between Brucella spp. and Ochrobactrum anthropi
      were investigated in animals and humans naturally infected by Brucella spp. and
      in experimentally infected rams (Brucella ovis infected), rabbits (Brucella
      melitensis infected), and mice (B. melitensis and Brucella abortus infected). In
      the animals tested, O. anthropi cytosolic proteins evoked a delayed-type
      hypersensitivity reaction of a frequency and intensity similar to that observed
      with B. melitensis brucellin. O. anthropi cytosolic proteins also reacted in gel
      precipitation tests with antibodies in sera from Brucella natural hosts with a
      frequency similar to that observed with B. melitensis proteins, and absorption
      experiments and immunoblotting showed antibodies to both Brucella-specific
      proteins and proteins common to Brucella and O. anthropi. No antibodies to O.
      anthropi cytosolic proteins were detected in the sera of Brucella-free hosts.
      Immunoblotting with sera of Brucella-infected sheep and goats showed
      immunoglobulin G (IgG) to Brucella group 3 outer membrane proteins and to O.
      anthropi proteins of similar molecular weight. No IgG to the O-specific
      polysaccharide of O. anthropi lipopolysaccharide was detected in the sera of
      Brucella-infected hosts. The sera of sheep, goats, and rabbits infected with B.
      melitensis contained IgG to O. anthropi rough lipopolysaccharide and lipid A, and
      B. ovis and O. anthropi rough lipopolysaccharides showed equal reactivities with
      IgG in the sera of B. ovis-infected rams. The findings show that the
      immunoresponse of Brucella-infected hosts to protein antigens is not necessarily
      specific for brucellae and suggest that the presence of O. anthropi or some
      related bacteria explains the previously described reactivities to Brucella rough
      lipopolysaccharide and outer membrane proteins in healthy animals.

PMID- 9144365
TI  - Comparison of the nucleic acids of helical and coccoid forms of Helicobacter
      pylori.
AB  - The nucleic acids of the helical and coccoid forms of Helicobacter pylori were
      studied to determine if the coccoid forms are "viable (capable of growing) but
      nonculturable." Using a reference strain (NCTC 11638) and five clinical strains,
      the nucleic acid contents, DNA integrity, and results of PCR and reverse
      transcription-PCR (RT-PCR) were compared for helical H. pylori and coccoid forms
      induced using glycochenodeoxycholic acid or bismuth citrate. The DNA and RNA
      contents of the coccoid forms were respectively 6.8- and 8.1-fold lower than
      those of helical H. pylori after 3 days of induction and 11.5- and 14.7-fold
      lower after 7 days. Agarose gel electrophoresis of DNA extracted from the coccoid
      forms after 3 days of induction showed a smear pattern indicating DNA cleavage,
      whereas DNA from helical H. pylori showed a single band with a high molecular
      mass. After 12 days of induction, all RNA samples from 100% coccoid cultures were
      negative for the mRNA of urease A or the 26-kDa species-specific protein by RT
      PCR. However, most RNA samples obtained after 3 or 7 days of induction were
      positive at low levels despite the lack of recovery from these cultures. These
      results suggest that the coccoid form of H. pylori has impaired genomic DNA and
      is in the process of cellular degeneration, thus being still alive but
      nonincreasable.

PMID- 9144366
TI  - Antigenic characterization of fimbria preparations from Streptococcus mutans
      isolates from caries-free and caries-susceptible subjects.
AB  - The adhesion of pathogenic bacteria to the host surface is an essential step in
      the development of numerous infections, including dental caries. Attachment of
      Streptococcus mutans, the main etiological agent of human dental caries, to the
      tooth surface may be mediated by glucan synthesized by glucosyltransferase (GTF)
      and by cell surface proteins, such as P1, which bind to salivary receptors.
      Fimbriae on the surfaces of many microorganisms are known to function in
      bacterial adhesion. Previous studies in this laboratory have initially
      characterized the fibrillar surface of S. mutans. The purpose of this
      investigation was the comparison of the antigenic properties of fimbria
      preparations of S. mutans isolates from five caries-resistant (CR) and six caries
      susceptible (CS) subjects. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis analysis of S. mutans fimbrial preparations revealed five major
      protein bands at 200, 175, 157, 86, and 66 kDa in preparations from CR and CS
      subjects. Immunoblot analysis indicated the presence of the same major bands
      recognized by anti-S. mutans fimbria antisera. Furthermore, the 175- and 157-kDa
      bands were recognized by antibodies to P1 and GTF, respectively. Immunoblot
      analysis with antisera to the fimbria preparation, to P1, or to GTF indicated
      that the levels of fimbria-reactive components and P1 and GTF antigens were
      higher in S. mutans fimbria preparations from CS subjects than in those from CR
      individuals. For example, four of six fimbria preparations from CS patients had
      demonstrable P1, and all had GTF. In contrast, only two of five CR fimbrial
      preparations exhibited P1 and GTF. Enzyme-linked immunosorbent assay demonstrated
      similar results for levels of GTF antigen in the fimbrial preparations from CR
      and CS subjects. The results suggest that differences between the compositions of
      S. mutans fimbriae in CR and CS individuals may play an important role in the
      virulence of this microorganism in dental caries.

PMID- 9144367
TI  - Baculovirus-expressed nonstructural protein NS2 of bluetongue virus induces a
      cytotoxic T-cell response in mice which affords partial protection.
AB  - Virus-specific cytotoxic T lymphocytes were generated in two strains of mice
      (BALB/c and CBA/Ca) against baculovirus recombinant proteins (minor and
      nonstructural) derived from bluetongue virus serotype 10. Immunization of mice
      with recombinant baculovirus insect cell extracts expressing the nonstructural
      protein NS2 (Bac-NS2) conferred partial protection against infection with
      vaccinia virus expressing the NS2 protein. This protective immunity was mediated
      by CD8+ cells. In contrast, no protection was observed when mice were immunized
      with similarly expressed Bac-NS1 or -NS3 or the virion minor structural proteins
      (Bac-VP1, -VP4, or -VP6). Furthermore, the in vitro cytotoxicity activity of T
      cells derived from immunized animals did not correlate to the protective efficacy
      of baculovirus recombinant proteins. The implications of this work with regard to
      the design of noninfectious subunit vaccines are discussed.

PMID- 9144369
TI  - Evaluation of a method for counting absolute numbers of cells with a flow
      cytometer.
AB  - We evaluated a method for performing absolute cell counts of lymphocyte
      populations with a flow cytometer. In this method, TruCount, test tubes that
      contain a known number of brightly fluorescent polystyrene beads are provided by
      the manufacturer. Whole anticoagulated blood is accurately pipetted into the
      tubes and mixed with fluorochrome-labeled monoclonal antibodies, the erythrocytes
      are lysed, and this mixture is analyzed on the flow cytometer. Absolute counts of
      lymphocyte subsets are calculated by determining the ratio of beads to the cell
      population of interest and then multiplying this ratio by the number of beads in
      the tube. We found this method to be reproducible. The values we obtained by the
      TruCount method were 5 to 10% higher than those obtained by conventional methods
      (flow cytometry and automated hematology) used to determine absolute numbers of
      cells. We believe that these differences are due to the methods of determining
      absolute cell counts and not to faulty identification of lymphocyte subsets.

PMID- 9144368
TI  - Antibody to human immunodeficiency virus type 1 (HIV-1) gp160 in mucosal
      specimens of asymptomatic HIV-1-infected volunteers parenterally immunized with
      an experimental recombinant HIV-1 IIIB gp160 vaccine. The National Institute of
      Allergy and Infectious Diseases-sponsored AIDS Vaccine Evaluation Group.
AB  - Twenty-two human immunodeficiency virus type 1 (HIV-1)-infected, asymptomatic
      volunteers with CD4 cell counts of >600 cells/mm3 who were enrolled in a phase I
      immunotherapy trial comparing two schedules of immunization of an HIV-1 IIIB
      based recombinant gp160 (rgp160) experimental vaccine were evaluated for rgp160
      specific antibodies in parotid saliva, genital secretions, and serum. When the
      study was unblinded, it was determined that five volunteers had received rgp160
      on a month 0, 1, 2, 3, 4, and 5 immunization schedule, seven volunteers had
      received rgp160 on a month 0, 1, 2, and 5 schedule, five had received
      alum/deoxycholate placebo, and seven had received a licensed hepatitis B virus
      vaccine. Five volunteers consented to the donation of parotid saliva but not
      genital secretions. Prior to immunization, parotid saliva specimens were
      available for 11 of 22 volunteers, seminal plasma (SP) specimens were available
      for 7 of 22 volunteers, cervicovaginal lavage (CVL) specimens were available for
      5 of 22 volunteers, and serum was available for 22 of 22 volunteers. These
      baseline specimens and specimens collected at 1 and 7 months after the final
      immunizations were assessed by enzyme-linked immunosorbent assay for
      immunoglobulin G (IgG) and IgA antibodies specific for HIV-1 LAI rgp160 or HIV-1
      MN rgp160. No augmentation in HIV rgp160-specific IgG or IgA antibody production
      in either parotid saliva or serum specimens of vaccinees compared to that in
      controls was observed after immunization. There were insufficient numbers of SP
      or CVL specimens available for statistical comparisons between vaccinees and
      controls. Overall, anti-LAI rgp160 IgG antibodies were detected in the parotid
      saliva specimens of 20 of 22 volunteers, the seminal plasma specimens of 11 of 11
      volunteers, and the CVL specimens of 6 of 6 volunteers and in 21 of 22 serum
      specimens. Fewer volunteers expressed anti-LAI rgp160 IgA antibodies in mucosal
      or serum specimens: 11 of 22 parotid saliva specimens, 3 of 11 SP specimens, 3 of
      5 CVL samples, and 12 of 22 sera.

PMID- 9144370
TI  - Modulatory effect of mycobacterium cell wall extract (Regressin) on lymphocyte
      blastogenic activity and macrophage cytokine gene transcription in swine.
AB  - Mycobacterium cell wall extract (MCWE) (Regressin) contains trehalose dimycolate
      and muramyl dipeptide, both of which have immunomodulatory properties. The goal
      of this study was to evaluate the effect of MCWE on the in vitro peripheral blood
      lymphocyte blastogenic activities to mitogens phytohemagglutinin (PHA) and
      concanavalin A (ConA) in 6- to 8-week-old piglets. The effect of MCWE on alveolar
      macrophage tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL
      1beta) gene transcription, as determined by a reverse transcription-PCR assay
      standardized with the endogenous glyceraldehyde-3-phosphate dehydrogenase gene,
      was also investigated. The results show enhanced blastogenic lymphocyte
      activities to mitogens PHA and ConA in MCWE-exposed cell cultures compared to
      those of control cell cultures. The enhanced blastogenic activity effect of MCWE
      was dose dependent. The cell background activity (spontaneous [3H]thymidine
      incorporation) of lymphocyte cultures was also significantly increased in the
      presence of MCWE, thereby demonstrating a lymphocyte mitogenic effect of MCWE.
      Cytokine gene transcription analysis showed that the TNF-alpha transcript levels
      in alveolar macrophage cell cultures stimulated with MCWE for 6 or 16 h were
      enhanced compared with those in control cell cultures. An enhancement of IL-1beta
      mRNA levels in cell cultures stimulated for 16 h with MCWE, compared with those
      in control cell cultures, was also observed. The overall results demonstrate that
      MCWE can stimulate lymphocyte functional activity and cytokine mRNA expression in
      swine, thereby indicating its potential use as a clinical immunotherapeutic
      agent.

PMID- 9144371
TI  - Protection of rats against Mycoplasma arthritidis-induced arthritis by active and
      passive immunizations with two surface antigens.
AB  - We previously identified two surface-exposed Mycoplasma arthritidis protein
      antigens, designated MAA1 and MAA2, that may be involved in cytadherence. Since
      adherence to host tissues is an important first step in most bacterial
      infections, we suggest that MAA1 and MAA2 may be virulence factors for M.
      arthritidis. In order to provide evidence for such a role, we conducted a series
      of experiments in which rats were actively immunized with each of these proteins
      purified from sodium dodecyl sulfate-polyacrylamide gels or passively immunized
      with poly- or monoclonal antibodies against MAA1 and MAA2. In each case, immunity
      against MAA1 and MAA2 conferred at least partial protection against M.
      arthritidis-induced disease. The greatest protection was achieved by passive
      immunization with monoclonal antibody A9a, directed against a surface-exposed
      epitope of putative adhesin MAA1. Because protective immunity in most bacterial
      infections is directed against major virulence factors, these results suggest
      that MAA1 and MAA2 may play a role in the pathogenesis of M. arthritidis-induced
      arthritis of rats, possibly by mediating initial colonization of joint tissues.

PMID- 9144372
TI  - Differential humoral response against alpha- and beta-linked mannose residues
      associated with tissue invasion by Candida albicans.
AB  - Candida albicans mannan is the major cell wall antigen that elicits antibodies
      considered to be of little diagnostic value. It comprises epitopes corresponding
      to sequences of alpha- and beta-1,2-linked mannose residues. Both types of
      oligomannosidic epitopes may also be present on the glycosidic portions of other
      C. albicans molecules, i.e., mannoproteins (MP) (either structural or enzymatic)
      and glycolipids. The human humoral responses against beta-1,2- and alpha-linked
      oligomannosides were investigated by C. albicans Western blotting by considering
      the elective distribution of beta-1,2-oligomannosidic epitopes over a 14- to 18
      kDa phospholipomannan (PLM) and the presence of alpha-mannosidic epitopes over
      heavily glycosylated MP. Western blotting of 51 control sera confirmed the
      presence of antibodies against C. albicans as a commensal member of the
      indigenous microflora; an immunoglobulin G (IgG) reactivity linked to enzyme
      linked immunosorbent assay mannan signals was found for both PLM (beta-1,2-Man
      residues) and MP (alpha-Man residues). Despite strong reactivities against mannan
      and MP, IgG from 21 hospitalized patients with mycological evidence of deep
      tissue invasion by C. albicans very significantly failed to react or reacted only
      faintly with PLM. This downregulation of anti-beta-1,2-oligomannosidic epitopes,
      associated with tissue invasion by C. albicans, was confirmed in 3 of 4 AIDS
      patients with extended oroesophageal candidosis. The application of a
      dissociation procedure proved that the absence of PLM reactivity was not due to
      the presence of immune complexes. These data provide the first evidence for a
      qualitative modification of the human antimannan antibody response associated
      with the C. albicans commensal-pathogenic transition.

PMID- 9144373
TI  - Immunoblot analysis for serodiagnosis of tuberculosis using a 45/47-kilodalton
      antigen complex of Mycobacterium tuberculosis.
AB  - We evaluated the immunoglobulin G (IgG) antibody response to the 45/47-kDa
      secreted protein of Mycobacterium tuberculosis by immunoblot assay, to assess its
      potential value for serological diagnosis. Control subjects consisted of healthy
      volunteers with negative or positive tuberculin skin tests. Most (>98%) scored
      negative in an immunoblot test when the sera were analyzed at a 1:400 dilution.
      Approximately 40% of sera (diluted 1 in 400) from tuberculous patients (positive
      smears) recognized the antigen complex. The sensitivity of the test for patients
      suffering from extrapulmonary tuberculosis was similar to that for patients
      suffering from pulmonary tuberculosis but who had negative smears. The frequency
      of positive reactions among the patients suffering from other pulmonary diseases
      was similar to that among the control subjects. In tuberculous patients infected
      with human immunodeficiency virus, the sensitivity of the immunoblot test was
      significantly lower. Thus, this test based on an antigen complex used in an
      immunoblot assay to detect the presence of IgG antibody has a specificity of 98%
      and a sensitivity of 40%. The simultaneous use of different purified antigens,
      selected at the same high specificity level, may improve the sensitivity of such
      an assay.

PMID- 9144374
TI  - High prevalence of Borna disease virus infection in healthy sheep in Japan.
AB  - Previous seroepidemiological and molecular epidemiological studies of Borna
      disease virus (BDV) showed considerably high rates of infection in horses,
      cattle, cats, and humans in Hokkaido, Japan. Here, we further demonstrate high
      rates of specific antibodies to BDV and BDV RNA in peripheral blood mononuclear
      cells (PBMCs) from healthy sheep bred on the same island. The BDV prevalences by
      immunoblotting and/or reverse transcriptase PCR were 0% (0 of 19) in newborns (<1
      month old), 51.7% (15 of 29) in lambs (1 to 6 months old), and 36.7% (11 of 30)
      in adults (>2 years old). Among animals positive for BDV, 60% of lambs and 45.5%
      of adults contained BDV RNA in PBMCs while 46.7% of lambs and 90.9% of adults
      contained specific antibodies to BDV. Thus, it is suggested that virus
      replication in the blood, as observed in lambs, is usually reduced in adulthood
      by raising immune responses to BDV.

PMID- 9144375
TI  - Measurement of antibodies against meningococcal capsular polysaccharides B and C
      in enzyme-linked immunosorbent assays: towards an improved surveillance of
      meningococcal disease.
AB  - In order to improve the surveillance of serogroup B and C meningococcal diseases,
      enzyme-linked immunosorbent assays (ELISAs) specific for anti-B immunoglobulin M
      (IgM) and anti-C IgM and IgG antibodies were developed. The tests were evaluated
      by using paired sera from 122 patients with and 101 patients without laboratory
      evidence of meningococcal disease. Fifty-three of 67 patients (79%) with culture
      confirmed serogroup B disease had an anti-B IgM antibody response; anti-B IgM
      levels waned rapidly in children < or = 4 years of age. Twenty-four of 25
      patients (96%) with culture-confirmed serogroup C disease had an anti-C IgM
      and/or IgG antibody response (IgM, 92%; IgG, 68%). In patients without evidence
      of meningococcal disease, 19% of children < or = 4 years of age and 69% of those
      > 4 years of age had intermediate anti-B IgM titers. In contrast, only 1 and 5%
      of these patients had intermediate titers of anti-C IgM and anti-C IgG,
      respectively. The ELISAs were shown to be powerful tools for discriminating
      between serogroup B and C diseases in 96 to 100% of culture-confirmed cases. For
      90% of patients with culture-negative meningococcal disease, a serogroup-specific
      diagnosis could be established by examination of paired sera in the ELISAs. As
      serogroup B and C meningococci account for practically all cases of meningococcal
      disease in industrialized countries, the availability of these tests may improve
      surveillance and prevention.

PMID- 9144376
TI  - L-2-oxothiazolidine-4-carboxylic acid inhibits human immunodeficiency virus type
      1 replication in mononuclear phagocytes and lymphocytes.
AB  - We investigated the effects of L-2-oxothiazolidine-4-carboxylic acid (OTC;
      Procysteine), a cysteine prodrug, on human immunodeficiency virus type 1 (HIV-1)
      expression in both adult peripheral and cord blood mononuclear phagocytes and
      lymphocytes. OTC suppressed HIV-1 expression in monocyte-derived macrophages
      (MDM) and lymphocytes in a dose-dependent fashion as determined by HIV-1 reverse
      transcriptase (RT) activity. This inhibitory effect of OTC occurred with three
      HIV-1 strains (two laboratory-adapted strains and one primary isolate). Addition
      of OTC to chronically HIV-1-infected MDM cultures also suppressed RT activity by
      40 to 50% in comparison to untreated controls. The inhibitory effects of OTC on
      HIV-1 were not caused by toxicity to MDM or lymphocytes because there was no
      change in cell viability or cellular DNA synthesis, as evaluated by trypan blue
      dye exclusion and [3H]thymidine incorporation, at doses of OTC that inhibit virus
      replication. These observations indicate that OTC has the potential to limit HIV
      1 replication in mononuclear phagocytes and lymphocytes and may be useful in the
      treatment of HIV-1 infection and AIDS.

PMID- 9144377
TI  - Function and phenotype of immature CD4+ lymphocytes in healthy infants and early
      lymphocyte activation in uninfected infants of human immunodeficiency virus
      infected mothers.
AB  - The function and phenotypes of CD4+ lymphocytes in infants are different than in
      adults and are modulated by maturational changes and exposure to environmental
      antigens. Infants of non-human immunodeficiency virus (HIV)-infected mothers and
      uninfected infants of HIV-infected mothers, 0 to 6 months of age, were examined
      for CD4+ lymphocyte function by in vitro interleukin-2 (IL-2) production and for
      CD4+ phenotypes by three-color flow cytometry. A minority of these uninfected
      infants (28%) had functional responses similar to those of healthy adult women
      (IL-2 production in response to anti-CD3, alloantigen, and mitogen), while the
      remainder were capable of responding to alloantigen and mitogen but not to anti
      CD3. We did demonstrate reduced phytohemagglutinin-stimulated IL-2 production in
      uninfected infants born to HIV-seropositive mothers compared to that in infants
      from seronegative mothers. The proportions of CD3+ CD4+, CD4+ HLA-DR- CD38+, and
      CD4+ CD45RA+ RO- (naive) lymphocytes were much higher in infants than in adults,
      and the proportions of CD4+ CD45RA- RO+ (memory) and CD4+ CD25+ (IL-2 receptor
      bearing) lymphocytes were lower in infants than in adults. The proportions of
      activated (CD4+ HLA-DR+ CD38+) and memory (CD4+ CD45RA- RO+) lymphocytes were
      increased in uninfected infants of HIV-infected mothers compared to infants of
      uninfected mothers. Therefore, T-helper-cell function is immature in many
      infants, but the CD4+ lymphocytes of some HIV-exposed, uninfected infants have
      been stimulated by antigen at an early age.

PMID- 9144378
TI  - Phagocytosis and killing of Staphylococcus aureus: effects of stress and
      depression in children.
AB  - While a large body of literature depicting relationships between depression or
      stress and immunity exists, few such studies have dealt with children, and none
      investigated myeloid cell-derived immunity. We investigated both phagocytosis and
      bactericidal activity against Staphylococcus aureus in children with major
      depressive disorder (MDD). We found that both MDD and stress influence the
      bactericidal but not the phagocytic activity of polymorphonuclear leukocytes. The
      data support the existence of psychobiologic effects in children and suggest
      possible mechanisms by which depression and stress may affect health.

PMID- 9144379
TI  - In vivo semen-associated pH neutralization of cervicovaginal secretions.
AB  - Physiological cervicovaginal acidity can partly inactivate human immunodeficiency
      virus (HIV). Basic semen components should be able to partially neutralize in
      vivo cervicovaginal pH. The goals of the study were to evaluate the relationship
      between cervicovaginal pH and presence of semen components in sexually active
      African women and to assess whether vaginal douching with water performed just
      after sexual intercourse could significantly reduce semen components and restore
      physiological cervicovaginal pH. Cervicovaginal secretion (CVS) from 56
      heterosexual African women (19 to 45 years old), living in Bangui, Central
      African Republic, were evaluated for pH, semen components (prostatic acid
      phosphatase [PAP] and prostatic specific antigen [PSA]), cellularity, and
      hemoglobin at inclusion and after vaginal douching with 100 ml of water by using
      a bock. Before douching, semen components were found in 46 of 56 CVS (82%). The
      mean vaginal pH was 5.2 (range, 3.6 to 7.7), and concentrations of both PAP and
      PSA correlated positively and strongly with cervicovaginal pH (P < 0.001). After
      douching, semen components were found in 35 of 56 CVS (62%) (P = 0.03).
      Cervicovaginal PAP and PSA levels were significantly decreased (respectively, P <
      0.0001 and P < 0.01; PAP, -72%; PSA, -87%), as was the total cell count (-60%; P
      < 0.0001). Furthermore, in CVS previously positive for both PAP and PSA, the mean
      vaginal pH was significantly decreased (6.5 versus 5.3, P < 0.01); no genital
      bleeding was observed. Frequent persistence of semen in CVS from heterosexually
      active African women leads to a shift from acidity to neutrality that could favor
      male to female HIV transmission. Vaginal douching provides significant
      elimination of semen after sexual intercourse; it should be considered for study
      as a supplementary means for the prevention of heterosexual HIV transmission.

PMID- 9144380
TI  - Standardization of measurement of immunoglobulin-secreting cells in human
      peripheral circulation.
AB  - A sensitive, and at times the most sensitive, measurement of human vaccine
      immunogenicity is enumeration of antibody-secreting cells (ASC) in peripheral
      blood. However, this assay, which is inherently capable of measurement of the
      absolute number of antigen-specific ASC, is not standardized. Thus, quantitative
      comparison of results between laboratories is not currently possible. To address
      this issue, isotype-specific ASC were enumerated from paired fresh and
      cryopreserved mononuclear cell (MNC) preparations from healthy adult volunteers
      resident in either the United States (US group) or Egypt (EG group). Analysis of
      fresh cells from US volunteers revealed mean numbers of ASC per 10(6) MNC of 617,
      7,738, and 868 for immunoglobulin M (IgM), IgG, and IgA, respectively, whereas EG
      volunteers had 2,086, 7,580, and 1,677 ASC/10(6) MNC for the respective isotypes.
      Cryopreservation resulted in a slight reduction in group mean IgM, IgG, and IgA
      ASC (maximum reduction in group mean, 14%), but in no instance were results
      obtained with cryopreserved cells significantly lower than those obtained with
      fresh cells. To determine if cryopreservation affected the number of bacterial
      antigen-specific ASC detected, cells from a group of US adult volunteers who
      received a single oral dose of a mutated Escherichia coli heat-labile enterotoxin
      (LT(R192G)) were tested. There was no significant difference (P > 0.05) in the
      number of antigen-specific IgA or IgG ASC detected between fresh and
      cryopreserved MNC. The results support the views that ASC assays can be
      standardized to yield quantitative results and that the methodology can be
      changed to make the test more practical.

PMID- 9144382
TI  - Combined determination of Coxiella burnetii-specific immunoglobulin M (IgM) and
      IgA improves specificity in the diagnosis of acute Q fever.
AB  - Immunoglobulin M (IgM) and IgA responses in patients with acute Q fever were
      compared by enzyme-linked immunosorbent assay. An increase in both IgM and IgA
      was observed in paired sera from all 19 patients with acute Q fever, and both IgM
      and IgA levels showed good correlation with complement fixation test titers.
      Paired sera from 23 patients with infections other than Q fever were also tested.
      IgM levels were elevated in three of these patients, while IgA levels were
      elevated in three different patients (87% specificity for either IgM or IgA). As
      no patients in the disease control group showed elevated levels of both IgM and
      IgA, definition of a positive result as elevated levels of both IgM and IgA
      improved specificity to 100% without a decrease in sensitivity. This study
      indicates that detection of specific IgA is a useful adjunct to that of IgM in
      the diagnosis of acute Q fever.

PMID- 9144381
TI  - Neutralizing antibodies to type 1 and 2 bovine viral diarrhea viruses: detection
      by inhibition of viral cytopathology and infectivity by immunoperoxidase assay.
AB  - Neutralizing antibodies to type 1 and 2 bovine viral diarrhea virus (BVDV)
      strains were measured by a microtiter virus neutralization test (MVNT) in cell
      culture. Antibodies (neutralizing) were detected by inhibition of viral
      infectivity, by the absence of viral cytopathology for cytopathic strains, or by
      immunoperoxidase staining for noncytopathic strains. The immunoperoxidase-stained
      monolayers could be detected without the aid of light microscopy. Twenty BVDV
      strains were used as challenge viruses in the in vitro MVNT, including 14 type 1
      and 6 type 2 strains. Representative noncytopathic and cytopathic strains of both
      types were used. Positive control serum samples available for diagnostic testing
      contained both type 1 and type 2 BVDV antibodies. There did not appear to be
      major differences in antibody titers among the respective type strains,
      regardless of biotype (cytopathic or noncytopathic). In a study with sera from
      calves receiving a modified live virus or inactivated BVDV vaccine, the calves
      receiving type 1 strains responded with higher antibody titers to type 1 strains
      than to type 2 strains.

PMID- 9144384
TI  - Regulation of endothelial CD44 expression and endothelium-tumour cell
      interactions by hepatocyte growth factor/scatter factor.
AB  - Cancer metastasis involves the passage of tumour cells into and out of blood or
      lymphatic circulatory systems and requires their interaction with the endothelial
      cells lining these vessels. Hepatocyte growth factor/scatter factor (HGF/SF) is a
      multifunctional protein that enhances tumour cell motility and extracellular
      matrix invasion and has been implicated as a mediator of metastasis. In this
      study, we have investigated the effect of HGF/SF on tumour cell-endothelial cell
      interactions. A fluorescent tumour cell-endothelial cell attachment assay
      demonstrated that, following endothelial monolayer stimulation with HGF/SF,
      tumour cell attachment to endothelium is increased. Addition of anti-CD44
      antibodies in this assay inhibited the effects of HGF/SF. Western blotting
      studies showed that HGF/SF increased expression of the adhesion molecule CD44 in
      endothelial cells. These results were confirmed by both immunohistochemical
      staining and a cell-surface adhesion molecule ELISA. These results suggest that
      HGF/SF plays a key role in the initial adhesion mechanism between tumour cells
      and endothelial cells via up-regulation of CD44.

PMID- 9144383
TI  - Microplate hybridization for Borna disease virus RNA in human peripheral blood
      mononuclear cells.
AB  - We developed a simple and sensitive microplate hybridization procedure with which
      to identify Borna disease virus cDNA in amplified products from human peripheral
      blood mononuclear cells. The mean values for the positive PCR products were
      significant compared with those for any of the negative products, indicating that
      this method can be applied to rapidly diagnose a large number of clinical
      specimens.

PMID- 9144385
TI  - Human 5-HT5A receptor gene: systematic screening for DNA sequence variation and
      linkage mapping on chromosome 7q34-q36 using a polymorphism in the 5'
      untranslated region.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter that mediates a wide
      range of sensory, motor, and cortical functions by activating multiple 5-HT
      receptor subtypes. In the present study we performed a systematic mutation scan
      of the complete coding region of the 5-HT5A receptor to explore its variability
      in the general population. Investigating 46 unrelated healthy subjects by single
      strand conformation analysis no sequence changes of likely functional relevance
      were observed. The detection of a frequent G-->C substitution at position -19 was
      used for fine scale linkage mapping of the 5-HT5A gene. Employing a polymerase
      chain-reaction based assay we genotyped 7 CEPH families (Centre d'Etude du
      Polymorphisme Humaine) and mapped the receptor to genetic markers on chromosome
      7q34-q36.

PMID- 9144386
TI  - Differential tissue distribution of the beta- and gamma-subunits of human
      cytosolic platelet-activating factor acetylhydrolase (isoform I).
AB  - The cDNA for human platelet-activating factor acetylhydrolase (PAF-AH) beta
      subunit was cloned. The complete amino acid sequence deduced from cDNA contains
      229 amino acids and is completely identical with that of the bovine subunit.
      Moreover, the sequence of the human beta-subunit protein shows 62.4% identity
      with the human gamma-subunit at the amino acid level. Southern blot analysis
      suggested the presence of multiple genes and we indeed found another closely
      related pseudo gene. Northern blot analysis showed that the 4.0 kb transcript was
      expressed in all tissues tested, suggesting the ubiquitous distribution of the
      subunit protein. Differential distribution of beta- and gamma-subunits might
      suggest that the oligomeric structure of PAF-AH is different from tissue to
      tissue.

PMID- 9144387
TI  - Counter-regulation of T helper 1 cell proliferation by nitric oxide and
      interleukin-2.
AB  - It was reported previously that cloned Th1 cells, but not Th2 cells, raised to
      malaria antigens, produce nitric oxide (NO) when activated with specific antigen
      or mitogen. Furthermore, NO inhibits the proliferation of, and production of
      interleukin-2 (IL-2) and interferon-gamma by, Th1 but not Th2 cells. By dose
      response analysis, I demonstrate here that Th1 cells produce optimal levels of IL
      2 and a proliferative response, and no detectable NO, when stimulated with
      relatively low concentrations of antigen or mitogen in vitro. As the
      antigen/mitogen increased, however, high levels of NO were produced, accompanied
      by a concomitant reduction in IL-2 secretion and T cell proliferation. At the
      highest concentrations of antigen/mitogen examined, addition of recombinant IL-2
      reversed the NO-mediated downregulation of T cell proliferation. These results
      suggest that NO may serve as a self-regulatory molecule preventing the over
      expansion of Th1 cells. At the other extreme, exogenous IL-2 may act to counter
      regulate the suppressive effect of high concentrations of NO on Th1 cell
      proliferation, thereby maintaining homeostasis.

PMID- 9144388
TI  - Differential time-course and dose-response relationships of TCDD-induced CYP1B1,
      CYP1A1, and CYP1A2 proteins in rats.
AB  - This study examined the relationship between dose- and time-dependent hepatic
      localization of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and expression of
      CYP1B1, CYP1A1 and CYP1A2 proteins. A dose-dependent increase in hepatic TCDD in
      female Sprague-Dawley rats treated with 0.01-30.0 microg TCDD/kg was observed.
      TCDD induced CYP1A1 protein in rats treated with 0.3 microg TCDD/kg or higher.
      TCDD induced CYP1A2 and CYP1B1 proteins in rats treated with 1.0 microg TCDD/kg
      or higher. The in vivo ED50 (microg TCDD/kg) for TCDD-induced CYP1A1, CYP1A2 and
      CYP1B1 proteins were 0.22, 0.40 and 5.19, respectively. Hepatic accumulation of
      TCDD reached a maximum at 8 hours post dosing with a t1/2 of approximately 10
      days. TCDD-induced CYP1A1/CYP1A2 protein expression was increased time
      dependently, reaching a maximum at 3 days after dosing and remaining elevated for
      35 days. In contrast, TCDD-induced CYP1B1 protein showed significant expression
      at 3 days after dosing and decreased to basal concentrations by 35 days. This
      study demonstrates that TCDD exhibits differential dose-response and time-course
      relationships on hepatic localization and cytochrome P-450 protein expression.

PMID- 9144389
TI  - Expression of a fungal cellobiohydrolase in insect cells.
AB  - The gene for Trichoderma reesei cellobiohydrolase I (CBHI) was expressed with a
      recombinant baculovirus and high levels of secreted protein were produced in
      Spodoptera frugiperda and Trichoplusia ni insect cells. Electrophoretic analysis
      indicated that the recombinant CBHI (rCBHI) was similar in apparent molecular
      weight to the native form and immunoblotting with anti-CBHI monoclonal antibodies
      confirmed its identity. The rCBHI was easily purified by affinity and hydrophobic
      interaction chromatography and demonstrated enzymatic activity on soluble
      substrate.

PMID- 9144390
TI  - Estrogen effects on protein expressed by marrow stromal osteoblasts.
AB  - The aim of this study was to follow the changes of estrogen treatment on
      osteoblastic MBA-15 cells derived from marrow stromal origin. Following exposure
      to estrogen, the cells' patterns of protein synthesis and expression were
      monitored. The proteins synthesized by MBA-15 cells were identified in cell
      lysate fractionated to soluble proteins (SOL), cytoskeleton (CK), membrane and
      nuclei, and intermediate filaments (PL) fractions. These cellular fractions of
      the osteoblastic MBA-15 cell cultures were assayed on SDS-PAGE of total proteins
      or following radiolabeling of cells by [35S]-Methionine. Changes in cytoskeletal
      and membrane proteins of the control and treated cells were monitored by these
      assays. Reduction in expression of tubulin (TUB) and thropomyosin (TM) were
      observed by western blot analysis and of actin by fluorescein staining. A
      reduction in expression of an antigen highly expressed by osteogenic cells and
      detected by MoAb 85/12 was also observed in these cells. These experiments showed
      reduction in cytoskeletal and other cellular proteins in the stromal osteoblastic
      MBA-15 cells treated with 17beta-Estradiol in comparison to untreated cells.

PMID- 9144391
TI  - Screening of inhibitors of HIV-1 protease using an Escherichia coli cell assay.
AB  - To evaluate the available peptidic and pseudopeptidic inhibitors of HIV protease
      for their possible in vivo activity, a screening test using Escherichia coli was
      established. E. coli cells carrying the plasmid pET9c-PR containing the gene for
      HIV-1 protease under the control of a T7-promotor are grown in the absence and in
      the presence of inhibitors. The action of the toxic protease produced by the
      cells is counteracted by the inhibitors. Provided sufficient membrane
      permeability of the inhibitors exists, this results in accelerated cell growth.
      From the peptides known to be active in an in-vitro enzyme test, most compounds
      inhibit HIV protease only to a limited degree in this test. However, two short
      peptides (Ac-Ser-Tyr-Glu-Leu and Lys-Ile-Ser-Tyr-Asp-Tyr) protect cell growth to
      an considerabe extent, thus indicating that they reach the E. coli cytosol and
      there block HIV protease. Two pseudopeptides known to be very potent in the
      enzyme test (SDZ PRI 053 and CIBA 61755) also inhibit HIV-1 protease strongly in
      this cell growth test.

PMID- 9144392
TI  - Novel transglutaminase inhibitors reduce the cornified cell envelope formation.
AB  - Transglutaminase (TGase) is a calcium-dependent enzyme which catalyzes the iso
      peptide cross-link between peptide-bound glutamine and lysine in vivo. Though the
      cross-link is developed as a barrier function in the skin system, overexpression
      of this could invoke skin hyperkeratosis in psoriasis and roughness in aged skin.
      In former research, many strong irreversible TGase inhibitors failed application
      because of high cytotoxicity. We selected one peptide after primary screening of
      six synthetic peptides designed from domains of known TGase substrates. Then we
      attempted to reduce the size and finally obtained two tetrameric peptides. When
      we treated keratinocyte with these TGase inhibitors under calcium-induced
      differentiation, the formation of a cornified cell envelope (CE) was decreased to
      the same level of CE under proliferating conditions without cytotoxic effect.
      Therefore, we propose that these TGase inhibitors may be useful for solving the
      physiological hypercross-linking problems for pharmaceutical or cosmetic
      purposes.

PMID- 9144393
TI  - Foreign gene expression in the mouse testis by localized in vivo gene transfer.
AB  - In order to attain foreign gene expression in vivo in the testis of living mice,
      chloramphenicol acetyltransferase (CAT), firefly luciferase and bacterial lacZ
      reporter genes were transfected by microparticle bombardment and electroporation.
      The results showed that CAT reporter gene was expressed in a dose-dependent
      fashion. The X-gal staining showed that in some spermatogenic-like cells, the
      bacterial lacZ gene was also expressed by in vivo electroporation, but not by in
      vivo microparticle bombardment. The possibility of in vivo gene transfer to the
      spermatogenic cells of the mouse testis was further confirmed by the fact that
      the CAT reporter gene expression was testis-specific when driven by the mouse
      protamin 1 promoter. It was concluded, therefore, that in vivo microparticle
      bombardment and, especially, electroporation provide convenient and efficient
      means of gene transfer to the testis of living mice.

PMID- 9144394
TI  - Metal-catalyzed oxidation of extracellular matrix proteins disrupts integrin
      mediated adhesion of mesangial cells.
AB  - We undertook the present study to determine whether oxidation of extracellular
      matrix could alter RGD (arginine-glycine-aspartic acid)-integrin interaction in
      mesangial cells. Mesangial cells demonstrated significantly less adhesion to
      matrix oxidized using a metal-catalyzed oxidation system and lost their typical
      spindle-shaped morphology. N-tert-butyl-alpha-phenylnitrone reversed in part both
      oxidation and impaired adhesion to matrix. Mesangial cells adhered to plates
      coated with GRGDSP but demonstrated impaired adhesion to oxidized GRGDSP.
      Oxidation of this peptide was demonstrated using immunoblot analysis with an
      antibody to dinitrophenylhydrazine bound to carbonyl groups on oxidized amino
      acid residues. This represents the first report demonstrating that oxidative
      modification of extracellular matrix impairs integrin-mediated adhesion and
      suggests that the mechanism may be oxidative modification of one or more amino
      acids in the RGD sequence. These data suggest a new mechanism by which cell
      matrix interaction may be altered in disease states characterized by enhanced
      oxidative stress.

PMID- 9144395
TI  - Gross mosaic pattern of mitochondrial DNA deletions in skeletal muscle tissues of
      an individual adult human subject.
AB  - Using polymerase chain reaction techniques, the patterns of mitochondrial DNA
      deletions (which characteristically occur at low abundance during ageing) were
      compared in different skeletal muscle samples of an adult human subject. In one
      particular section of the biceps muscle, an unusual pattern of mitochondrial DNA
      deletions was detected; the common 4977 bp deletion was absent, but other
      deletions were observed. In pectoralis (chest) muscle, deletions commonly seen in
      normal adults were readily detected, including the 4977 bp deletion.
      Significantly, different patterns of mtDNA deletions were found in two adjacent
      parts of the same biceps muscle sample: one was the unusual pattern mentioned
      above, but the other part clearly contained the 4977 bp deletion. The results
      therefore demonstrate a gross mosaic pattern of mtDNA deletions in the skeletal
      muscle tissues of an individual human subject.

PMID- 9144396
TI  - Localization of a calcium sensitive binding site for gelsolin on actin subdomain
      I: implication for severing process.
AB  - The binding of the N-terminal domain (S1) of gelsolin to monomeric actin has been
      extensively documented. In contrast, the location of the C-terminal calcium
      dependent domains (S4-6) interacting with the actin filament during the severing
      process remains uncertain. In this study, we have identified a new interface that
      supports calcium dependent gelsolin binding to actin. This site is located in a
      critical position towards actin-actin contact in the filament and in the vicinity
      of the phalloidin site. Using specific antibody and synthetic peptides derived
      from actin sequence within 105-132 residues, this interface was finally ascribed
      to the segment 112-120 on the actin subdomain-1.

PMID- 9144397
TI  - Tetrahydrobiopterin synthesis precedes nitric oxide-dependent inhibition of
      insulin secretion in INS-1 rat pancreatic beta-cells.
AB  - Interleukin 1 (IL-1) induces pancreatic beta-cell dysfunction mainly due to
      overproduction of nitric oxide (NO). Since tetrahydrobiopterin (BH4) is a
      obligatory cofactor of NO synthases, we examined the temporal relationship of BH4
      synthesis, NO production and insulin secretion in a pancreatic beta-cell line
      (INS-1) which was exposed to IL-1. IL-1 affected BH4 synthesis in a time- and
      concentration-dependent manner. At a concentration of 10 ng/ml IL-1 caused an
      increase in intracellular BH4 with peak levels being observed at 6 hours followed
      by a steady decline in the cellular BH4 content. The increase in BH4 synthesis
      was followed by enhanced NO production and, consecutively, inhibition of insulin
      secretion. The concentration-dependent regulation of BH4 synthesis, NO production
      and suppression of insulin secretion indicate a functional link between these
      parameters in pancreatic beta-cells.

PMID- 9144398
TI  - Characterization of extracellular nucleotide-induced Mac-1 (alphaM beta2
      integrin) surface expression on peripheral blood leukocytes.
AB  - Extracellular nucleotides, released during vascular injury, stimulate
      hematopoietic cells resulting in various physiological responses. We have
      determined that nucleotides can stimulate the expression of Mac-1 on peripheral
      blood leukocytes. ATP stimulated the expression of Mac-1 in a time- and dose
      dependent manner with maximum expression occurring in 5 min at 10 microM ATP.
      This increase in surface expression was observed in monocytes and granulocytes
      was dose-dependent and was comparable in extent to the increase induced by the
      chemotactic peptide, formyl-Met-Leu-Phe. Other nucleotides including 2-MeSADP,
      ADP, UTP, and 2MeSATP had similar effect. Nucleotide-mediated stimulation of Mac
      1 expression in granulocytes was completely inhibited by Ro-31-8220, a specific
      inhibitor of protein kinase C, while variable inhibition was observed in
      monocytes. These results demonstrate the stimulation of peripheral blood
      leukocytes by nucleotides causing an increased surface expression of Mac-1 which
      may be mediated by the activation of protein kinase C.

PMID- 9144399
TI  - Changes in the molecular structure of hair in insulin-dependent diabetes.
AB  - Low-angle synchrotron X-ray diffraction has revealed clear and consistent changes
      in the molecular structure of alpha-keratin of hair in insulin-dependent diabetes
      (IDDM) both for human IDDM subjects and for baboons with streptozocin induced
      diabetes. These changes in both meridional and equatorial intensity distributions
      are fully explained by a newly developed hexagonally packed model for keratin
      which locates the modification produced in hair in IDDM in the labile structure
      of the matrix at established intermediate filament linkage sites. The nature of
      the extracellular bonding suggests that the change is endogenous, occurring via
      the blood during the aggregation of the IFs in the follicle. The reproducibility
      of these changes indicate that hair may represent an easily accessible tissue for
      the study of how hyperglycaemia can modify extracellular matrix materials which
      lead to diabetic complications.

PMID- 9144400
TI  - Osteopontin gene expression and protein synthesis in cultured rat mesangial
      cells.
AB  - It is controversial whether osteopontin (OP) is expressed in glomeruli and
      involved in glomerular diseases. We examined whether the OP expression is present
      at gene and protein levels in cultured rat mesangial cells (MCs). Northern
      blotting revealed a 1.7 kb OP-mRNA expression in MCs. Fetal calf serum (FCS) and
      TNF-alpha increased OP gene expression in serum-starved MCs by 2.7- and 1.8-fold
      over 24- and 12-hour periods, respectively. PDGF, IL-1beta, and TGF-beta had
      little effect on OP gene expression. Western blotting detected the OP protein
      expression (69 kDa). FCS and TNF-alpha increased OP protein expression in serum
      starved MCs over 48- and 24-hour periods, respectively. The present study clearly
      demonstrated the expression of OP gene and protein in cultured rat MCs. Increased
      OP production under serum or TNF-alpha stimulation suggests that intraglomerular
      OP may contribute to the development of glomerular diseases.

PMID- 9144401
TI  - Genistein inhibits Na+/Ca2+ exchange activity in primary rat cortical neuron
      culture.
AB  - We have examined the possible regulatory effect of tyrosine kinase activity on
      Ca2+ transport observed in the cultured rat cortical neurons. Na+/Ca2+ exchange
      was studied using cells cultured for various time periods. A nearly two fold
      increase in Ca2+ uptake was seen when comparing 3 day and 9 day cultures. Western
      blot analysis also showed a two fold increase in Na+/Ca2+ exchanger (NCX1)
      protein levels as cells matured in culture. To study the effect of genistein (a
      specific tyrosine kinase inhibitor) cells were incubated with 100 microM
      genistein (in 1% DMSO) for 1 hour before the assay of Na+/Ca2+ exchange activity.
      There was a significant decrease of Ca2+ uptake in genistein treated neurons
      (control: 4.596+/-0.205 nmol/mg protein/15 min, n=12; genistein: 1.420+/-0.131
      nmol/mg protein/15 min, n=12, mean+/-S.E. P<0.001). Daidzein, an inactive analog
      of genistein and phorbol myristate acetate (PMA), a PKC activator were without
      effect. The results suggest that as cells mature in culture, Na+/Ca2+ exchange
      capacity increases, as a result of greater protein expression. Exposure to
      genistein inhibited Ca2+ uptake suggesting that the exchanger may be modulated by
      tyrosine phosphorylation.

PMID- 9144402
TI  - DNA binding preferences of PPAR alpha/RXR alpha heterodimers.
AB  - The regulatory elements mediating the transcriptional effects of the Peroxisome
      Proliferator Activated Receptor (PPAR)/Retinoid X Receptor heterodimers consist
      of a direct repeat of a variant of the consensus hexamer AGGTCA with an
      interspacing of 1 basepair (DR1). A binding site selection was performed to
      investigate whether any further constraints for PPAR/RXR binding to DR1 elements
      exist and/or whether other high affinity binding sites for these heterodimers can
      be identified. One half of the recovered sequences contained two hexamers related
      to the consensus halfsite organised as DR1, DR2, PAL0 or as DR3, in diminishing
      order of frequency. The other binding sites consisted of three hexamer repeats
      with the number of interspacing bases varying between 0 and 7. An element with
      three consecutive hexamer sequences each spaced by 1 basepair was most efficient
      in mediating the effects of peroxisome proliferators. The results indicate that
      the upstream flanking sequence of a DR1 differentially influences the binding of
      PPAR alpha/RXR alpha heterodimers and of RXR alpha homodimers.

PMID- 9144403
TI  - Two different proteases are involved in the proteolysis of lamin during
      apoptosis.
AB  - To investigate the involvement of different proteases in the execution step of
      apoptosis and to determine their intracellular location, isolated rat thymocyte
      nuclei were incubated either in the presence of Ca2+ and Mg2+ or with cytosolic
      extract from Jurkat T lymphocytes treated with anti-Fas (APO-1, CD-95) antibody.
      Inhibitors of caspases, VADcmk and DEVDcho, were not effective in hindering Ca2+
      induced apoptotic changes in isolated nuclei, but did prevent similar changes in
      nuclei treated with the cytosolic extract from apoptotic Jurkat cells. In
      contrast, the inhibitor of the Ca2+-regulated, nuclear scaffold-associated serine
      protease, AAPFcmk, was able to inhibit lamin B1 breakdown, as well as chromatin
      cleavage in nuclei incubated in the presence of Ca2+ and Mg2+, but only partially
      prevented the same changes induced with cytosolic extract. Our findings provide
      evidence for the involvement of at least two proteases in lamin cleavage. One
      belongs to the caspase family and to cleave lamins this enzyme must be
      translocated from the cytoplasm into the nucleus. The second protease has a
      nuclear location and is activated by Ca2+. Finally, neither of these two lamin
      cleaving proteases is responsible for the cleavage of another nuclear target
      protein, poly(ADP-ribose)polymerase (PARP), during apoptosis.

PMID- 9144404
TI  - Quantification of wild-type mitochondrial DNA and its 4.8-kb deletion in rat
      organs.
AB  - Oxidative damage to mitochondrial DNA (mtDNA) is considered a major contributor
      in aging. An age-dependent increase of oxidative damage and of the quantity of
      partially deleted mtDNA was reported for several rat and human organs. Here, a
      systematic investigation of ten different tissues and organs of 20-months-old
      rats was performed. The amount of mtDNA and age-dependent 4.8 kb deletion (delta
      mtDNA4834) was determined by competitive polymerase chain reaction, along with
      the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSHPx).
      The data were related to the corresponding metabolic rates. MtDNA content was
      highest in heart and lowest in spleen. delta mtDNA4834 was detected in all ten
      tissues and organs, and its amount was highest in liver and lowest in intestine.
      In heart, lung, muscle, and bone-marrow the deletion could not be quantified
      because of a point mutation, an A-->T transition at position 8107. Activities of
      SOD and GSHPx were highest in liver and lowest in intestinal mucosa. A negative
      correlation between mtDNA content and delta mtDNA4834, and a positive correlation
      between metabolic rate, GSHPx, and the deletion was found. These results suggest
      that the occurrence of delta mtDNA4834 in rat is related to oxidative stress.

PMID- 9144405
TI  - Luteinizing hormone increases the abundance of various transcripts, independently
      of the androgens, in the rat prostate.
AB  - Differential display analysis was carried out to find, in the rat prostate, genes
      that could be regulated by Luteinizing Hormone (LH), independently of the
      androgens. Hypophysectomized and castrated adult rats were treated with either
      LH, testosterone or saline. Regulated discrete bands have been eluted and
      reamplified. After Northern blotting, the levels of mRNA corresponding to 8 PCR
      fragments were significantly increased by LH treatment. None of these inserts
      were found to be induced by testosterone. One insert was subcloned, sequenced and
      identified as the ribosomial protein S 23. A competitive RT-PCR assay was carried
      out on the full length S 23 cDNA and confirmed that its mRNA levels were
      stimulated by LH but not by testosterone. These results strongly suggest that the
      LH membrane receptor, previously shown to be expressed in the rat prostate, has a
      physiological significance in this organ. Moreover, it appears that the effect of
      LH on the rat prostate are independent of the androgens.

PMID- 9144406
TI  - Developmentally regulated expression of APG-1, a member of heat shock protein 110
      family in murine male germ cells.
AB  - Apg-1 encodes a heat shock protein belonging to the heat shock protein 110
      family, and is inducible by a 32 degrees C to 39 degrees C heat shock. Northern
      blot analysis of the testis from immature and adult mice, and of the purified
      germ cells revealed the quantitative change of the apg-1 transcripts during germ
      cell development. By in situ hybridization histochemistry the expressions of the
      apg-1 transcripts were detected in germ cells at specific stages of development
      including spermatocytes and spermatids. Although heat-induction of the apg-1
      transcripts was observed in W/Wv mutant testis lacking germ cells, it was not
      detected in wild-type testis nor in the purified germ cells. Thus, the apg-1
      expression is not heat-regulated but developmentally regulated in germ cells,
      suggesting that APG-1 plays a role in normal development of germ cells.

PMID- 9144407
TI  - Molecular cloning and characterization of a novel putative carboxylesterase,
      present in human intestine and liver.
AB  - A full-length cDNA coding for a putative intestinal carboxylesterase (iCE) was
      isolated from a human small intestine cDNA library. The cDNA has an open reading
      frame of 559 amino acids with up to 65% homology to other carboxylesterases of
      different mammalian species. The deduced amino-acid sequence contains many
      structural features, that are highly conserved among all carboxylesterase
      isoenzymes, like the serine esterase active site, an ER-retention signal and one
      Asn-Xxx-Thr site for N-linked carbohydrate addition. Northern blot analysis
      revealed that the corresponding mRNA is 3.4-3.6 kb in size and is preferentially
      expressed in human intestine with a weak signal also in liver. Analysis of cells
      from the gastrointestinal tract unveiled site-specific, transcriptional
      regulation of iCE, with higher expression in small intestine and lower expression
      in colon and rectum. The high expression in small intestine is attributable to a
      higher expression in jejunum compared to duodenum and ileum.

PMID- 9144409
TI  - Binding sequence of STAT4: STAT4 complex recognizes the IFN-gamma activation site
      (GAS)-like sequence (T/A)TTCC(C/G)GGAA(T/A).
AB  - Studies of transcriptional activation by interferons and various cytokines have
      led to the identification of a family of proteins that serve as signal
      transducers and activators of transcription (STAT). STAT4 is phosphorylated
      following interleukin (IL)-12 stimulation and is required for IL-12 signal
      transduction. By immunoprecipitation and PCR amplification, a specific consensus
      sequence for DNA binding of the STAT4 complex was determined. The binding
      sequence of the STAT4 complex, (T/A)TTCC(C/G)GGAA(T/A), proved to be palindromic
      and similar to the IFN-gamma activated site (GAS)-like sequence. The first (T/A)
      and last (T/A) sites of the consensus sequence were critical for the binding
      affinity of the STAT4 complex.

PMID- 9144408
TI  - Action mechanism of retinoid-synergistic dibenzodiazepines.
AB  - 4-[5H-2,3-(2,5-Dimethyl-2,5-hexano)-5-methyldibenzo[b,e][1,4 ]diazepin-11
      yl]benzoic acid (HX600), as well as its oxa- (HX620) and thia- (HX630) analogs,
      enhanced the activity of retinoic acid and a receptor alpha (RAR alpha)-selective
      agonist Am80 in HL-60 cell differentiation assays. HX600 synergizes with Am80 by
      binding to, and transactivating through, the RXR subunit of the RXR-RAR
      heterodimer. HX600 exhibited RXR pan-agonist activity in transient transfections
      with a DR1-based reporter gene and synergized with RA-bound RAR alpha and RAR
      beta in inducing transcription from a DR5-based reporter. In addition, all three
      compounds at high concentrations acted as RAR pan-antagonists in stably
      transfected RAR "reporter cells." These efficient synergists bind only weakly
      with RXRs in vitro, suggesting that they are RXR-RAR heterodimer-selective
      activators. These HX retinoids exhibited dual functionality, since they affected
      signalling through both retinoid receptor families (RARs and RXRs).

PMID- 9144410
TI  - Mg2+- or Mn2+-dependent endonuclease activities of human myeloid leukemia cells
      capable of producing nucleosomal-size DNA fragmentation.
AB  - The presence of at least two distinct Mg2+- or Mn2+-dependent, Ca2+-independent
      endonuclease activities was shown in the myeloid leukemia cell line P39. One of
      them was recovered from nuclear extracts and the other from a cytoplasmic
      fraction. The molecular size of the former was 30 kDa in both gel filtration and
      activity gel and that of the latter approximately 130-140 kDa in gel filtration
      and 65-70 kDa in activity gel. These two activities were almost completely
      inhibited by 0.1 mM ZnCl2 or 0.1 mM aurintricarboxylic acid, common inhibitors of
      apoptosis. Both could produce nucleosomal-size DNA fragmentation when incubated
      with diethyl-pyrocarbonate-treated nuclei as substrates, and the pattern of
      cleavage was 3'-OH and 5'-P. Taken together, either or both of these activities
      may be associated with apoptosis of myeloid leukemia cells.

PMID- 9144411
TI  - Several synthetic chemicals inhibit progesterone receptor-mediated
      transactivation in yeast.
AB  - The human progesterone receptor (hPR) B-form and a progesterone-sensitive
      reporter were expressed in yeast and used to screen a library of synthetic
      chemicals for their ability to function as agonists or antagonists of hPR. The
      transcriptional activity of hPR was not increased in the presence of over 40
      individual chemicals. Seven chemicals decreased progesterone-dependent activity
      in yeast. The most effective chemicals were 6-hydroxychrysene, 1-hydroxypyrene, 4
      hydroxy, 2',4',6'-trichloro biphenyl, and 4-hydroxy, 2',3',4',5'-tetrachloro
      biphenyl. The decrease of progesterone-mediated transactivation strongly
      correlated with their displacement of [3H]progesterone from hPR. The absence of
      the hydroxyl group on the above chemicals completely abolished their inhibitory
      activity. The other chemicals which decreased progesterone activity were
      endosulfan II, endosulfan sulfate, and lindane. These chemicals did not inhibit
      [3H]progesterone binding, suggesting that they inhibit progesterone action by
      interacting with a region of hPR distinct from binding [3H]progesterone or by a
      mechanism independent of hPR. These results highlight the utility of yeast for
      screening hormonally-active chemicals. In addition, hydroxylation appears to be
      essential for the interaction of some chemicals with hPR.

PMID- 9144412
TI  - Inhibition of melibiose transporter by amiloride in Escherichia coli.
AB  - Amiloride inhibited the active transport of melibiose via the melibiose
      transporter in Escherichia coli. Since amiloride is known to inhibit the Na+/H+
      antiporter which is essential for the establishment of an electrochemical
      potential of Na+ that is the driving force for melibiose transport, we tested the
      effect of amiloride on the activity of the melibiose transporter itself.
      Amiloride inhibited the melibiose counterflow. Also, inhibition of Na+ uptake
      induced by melibiose influx and some inhibition of H+ uptake induced by melibiose
      influx were observed. These results indicate that amiloride directly inhibits the
      melibiose transporter, perhaps by competing with Na+. It seems that the Na+
      binding site and the H+ binding site in the melibiose transporter are somehow
      different from each other judging from the difference in the inhibition pattern
      of amiloride.

PMID- 9144413
TI  - A novel nonenzymatic pathway for the generation of nitric oxide by the reaction
      of hydrogen peroxide and D- or L-arginine.
AB  - Nitric oxide (NO) is a biologically active molecule known to be enzymatically
      synthesized from L-arginine in the presence of NO synthetase (NOS). In this
      study, we demonstrate a novel non-enzymatic pathway for NO synthesis involving
      hydrogen peroxide and D- or L-arginine. We employed two measures of NO
      generation. The first consists in the demonstration of the oxidative metabolites
      of NO (NO2 + NO3 = NOx) and the second is the confirmatory finding of
      chemiluminescence derived from NO. The results show that NOx increases in the
      incubation mixture containing hydrogen peroxide coupled with D-arginine, L
      arginine, L-canavanine, and even the NOS inhibitor N(G)-nitro-L-arginine methyl
      ester (L-NAME). However, chemiluminescence was detected only from the reactions
      of hydrogen peroxide and D- or L-arginine and was diminished by the addition of
      carboxy-2-phenyl-4, 4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (PTIO), a
      specific scavenger of NO, confirming NO generation in the reaction.

PMID- 9144414
TI  - Overexpression of ZBP-89, a zinc finger DNA binding protein, in gastric cancer.
AB  - ZBP-89 is a Kruppel-type zinc finger protein that binds to the gastrin EGF
      response element (gERE). Sp1 binds to the same DNA element and transactivates
      gastrin promoter activity, whereas ZBP-89 competes for Sp1 binding and prevents
      EGF induction. Both transcription factors mediate growth factor signals
      originating from the EGF receptor and thus were studied in normal and neoplastic
      tissues or cell lines. When compared to normal tissue from the same patient, ZBP
      89 protein expression was increased in neoplastic tissue from the stomach antrum
      and in malignant cell lines. RT-PCR analysis of ZBP-89 mRNA correlated with
      protein overexpression. Immunocytochemical studies confirmed that ZBP-89
      expression is elevated in neoplastic tissue and chronic gastritis, whereas Sp1
      expression was nearly unchanged. These results suggest that the transcription
      factor ZBP-89, like Sp1, may be a marker for neoplastic transformation in some
      gastric cancers.

PMID- 9144416
TI  - Subtype specific recognition of human alpha2C2 adrenergic receptor using
      monoclonal antibodies against the third intracellular loop.
AB  - Monoclonal antibodies (Mabs) against human alpha2C2-adrenergic receptor (alpha2C2
      AR) were raised in mice and characterized. Bacterially expressed fusion protein
      consisting a sequence from the putative third intracellular loop (amino acids 213
      343) of human alpha2C2 and glutathione-S-transferase (GST) was used as antigen.
      Results from mass spectrometry of purified thrombin cleaved alpha2C2 polypeptide
      suggested that the epitope region would lie near the aminoterminal end of the 3rd
      intracellular loop of human alpha2C2-AR. Elevation of Mabs was detected with
      Western blotting from mouse blood samples. Three alpha2C2 specific cell clones
      were expanded to in vitro production in hollow fiber systems. The specificity of
      the Mabs was further determined by immunoprecipitation and immunocytochemistry.
      Scatchard analysis of thrombin digested, purified, Europium-labelled antigen
      (amino acids 213-343 of alpha2C2) revealed binding affinity constants of 0.4 x
      10(9), 0.7 x 10(9) and 1.6 x 10(9) M(-1) and Kds of 2.6, 1.4 and 0.6 nM for the
      three Mabs 2B1, 3G3 and 7G1, respectively.

PMID- 9144415
TI  - Nasal and pharyngeal abnormalities caused by the mouse goosecoid gene mutation.
AB  - The Goosecoid (gsc) gene is a homeobox-containing gene expressed first in the
      gastrula, and later during organogenesis in development. The gsc gene transcript
      is found in the first and second branchial arches, frontonasal mass in its late
      phase of expression. We have previously shown that targeted mutation of the mouse
      gsc gene leads to neonatal death and craniofacial defects. In this study, we
      performed histological studies on craniofacial phenotypes in order to elucidate
      the processes underlying the neonatal death of gsc mutant mice. We found that gsc
      mutant mice have aplastic nasal cavities and lack the Sinus Paranasalis. We also
      showed that secretory olfactory glands in the basal layers are aplastic. This is
      suggested to be essential defects for olfaction. gsc mutant mice also show
      several pharyngeal phenotypes, including defects in the pharyngeal muscles and
      the pharyngeal mucosa. It is therefore suggested that mutant mice develop lethal
      gastro-intestinal phenotypes caused by defects in breathing and sucking of milk
      as a consequence of these craniofacial disorders. These results should help
      elucidating the molecular genetic programs essential to the neonatal development
      of mammals.

PMID- 9144417
TI  - In vivo experimental studies on the role of free radicals in photodynamic
      therapy. III. Photodynamic effect on free radicals generated in cell cultures.
AB  - The effect of excited Photofrin II molecules on the zymosan stimulated and
      luminol dependent chemiluminescence (CL) of macrophages, known as respiratory
      burst, has been studied. Excitation was carried out by light irradiation in the
      vicinity of the maximal CL by varying light doses. In separate experiments
      potassium salt of 3,5-di-tert-butyl-4-hydroxyphenyl propionic acid radical
      inhibitor was added to the system and its consumption measured spectroscopically.
      Based on the experimental results the decrease in the steady state radical
      concentrations under the influence of radical inhibitor and of triplet sensitizer
      generated in situ has been calculated. It has been established that the
      corresponding photodynamic effect is an inhibition-like process proceeding by
      triplet-doublet interactions.

PMID- 9144418
TI  - Transgenic copper/zinc-superoxide dismutase ameliorates caerulein-induced
      pancreatitis in mice.
AB  - The role of oxidative stress in acute pancreatitis was investigated by comparing
      the pathological features of caerulein pancreatitis between transgenic mice that
      overexpress human Cu/Zn-superoxide dismutase (SOD) and nontransgenic littermates.
      Both the elevation of serum amylase and the formation of pancreatic edema during
      the pancreatitis were significantly reduced in the transgenic mice compared with
      the nontransgenic littermates. In the transgenic mice, the pancreatitis
      associated reduction of Cu/Zn-SOD activity in the pancreatic tissues was
      significantly smaller than that in the nontransgenic mice. These results provide
      direct evidence that the elevation of intracellular oxygen radicals is an
      important factor for the progress of acute edematous pancreatitis.

PMID- 9144419
TI  - Integrin beta4 is involved in apoptotic signal transduction in endothelial cells.
AB  - To clarify the signal transduction in vascular endothelial cells (VEC) apoptosis
      induced by deprivation of FGF and serum, we investigated the function of integrin
      beta4 by using the monoclonal antibody (mAb) of this integrin. We added anti-beta
      4 integrin mAb at the concentration of 5 microg/ml to the cells deprived of FGF
      and serum, apoptosis of these cells were completely inhibited 24 h after the
      treatment. Furthermore we plated the cells onto untreated bacterial culture
      plates on which the cells cannot adhere and spread in MCDB medium without FGF and
      serum; however, when anti-beta 4 integrin mAb was present at 5 microg/ml in the
      seeding medium, the cells rapidly adhered and spread. Our results first
      demonstrated that integrin beta4 participated in apoptotic signaling in VEC, and
      our findings indicate that hemidesmosome structures and keratin filament system
      might be important in regulation of apoptotic signaling.

PMID- 9144420
TI  - Involvement of a common 10-amino-acid segment in the cytoplasmic region of CD40
      but different MAP kinases in different CD40-mediated responses.
AB  - CD40-mediated signals can induce cell aggregation, proliferation and rescue from
      apoptosis in WEHI231. To define which segment of cytoplasmic domain of CD40 and
      how signals are involved in those events, we generated mutant CD40 transfectants.
      We demonstrated the same 10 amino acid segment that could bind to tumor necrosis
      factor receptor associated factor-2 and -3 mediated all those responses. However,
      activation pattern of mitogen activated protein kinases was different.
      Immunoglobulin M-mediated apoptosis was inhibited by CD40-mediated signal that
      activated c-Jun aminoterminal kinase synergistically. While, CD40 stimulus
      through the 10 amino acid segment alone that induced cell aggregation and
      proliferation resulted in activation of extracellular signal-regulated protein
      kinase 2.

PMID- 9144421
TI  - Regulation of thrombin-induced stress fibre formation in Swiss 3T3 cells by the
      70-kDa S6 kinase.
AB  - The signal transduction systems that mediate growth factor receptor-induced
      cellular shape change have not been fully elucidated, but are known to involve
      alterations in the state of actin filaments, termed stress fibres. It now appears
      from several studies that the GTP-binding protein, Rho, is involved. However, the
      mechanisms by which Rho is activated, and what effectors Rho in turn stimulates
      are largely matters of conjecture. The present work shows that thrombin is an
      effective stimulant of stress fibre formation in Swiss 3T3 cells. In addition, we
      show the 70 kDa form of S6 kinase (p70s6k) to colocalise with stress fibres in
      both unstimulated and thrombin-activated cells. Coincident with the thrombin
      induced formation of stress fibres is the elevated association p70s6k with the
      fibres. Pretreatment of cells with rapamycin, to inhibit p70s6k activation,
      inhibits thrombin-induced stress fibre formation and the associated presence of
      p70s6k on the fibres, supporting a role for p70s6k in thrombin-stimulated stress
      fibre formation. Thrombin is also shown to stimulate p70s6k activity and that
      this is inhibited by rapamycin. Thus, the data presented show that thrombin
      activates stress fibre formation through stimulation of p70s6k via a non-Gi
      pathway.

PMID- 9144422
TI  - Prostaglandin F2alpha receptor (FP receptor) agonists are potent adipose
      differentiation inhibitors for primary culture of adipocyte precursors in defined
      medium.
AB  - Prostaglandin F2alpha inhibits adipose differentiation of primary culture of
      adipocyte precursors and of the adipogenic cell line 1246 in defined medium. In
      the present paper, we investigated the effect of FP receptor agonists
      cloprostenol and fluprostenol on the differentiation of newborn rat adipocyte
      precursors in primary culture. The results show that cloprostenol and
      fluprostenol are very potent inhibitors of adipose differentiation. Dose response
      studies indicate that both agonists are more potent than PGF2alpha in inhibiting
      adipocyte precursors differentiation. 50% inhibition of adipose differentiation
      was observed at a concentration of 3 x 10(-12) M for cloprostenol and 3 to 10 x
      10(-11) M for fluprostenol respectively whereas the PGF2alpha concentration
      required to elicit the same effect was 10(-8) M. In contrast compounds
      structurally related to PGE2 such as 17-phenyl trinor PGE2 had no effect on
      adipose differentiation except when added at a 10,000-fold higher concentration.

PMID- 9144423
TI  - Follicle-stimulating hormone activates a cAMP-dependent chloride conductance in
      TM4 Sertoli cells.
AB  - The effect of follicle-stimulating hormone (FSH) on the electrical properties of
      TM4-Sertoli cells was investigated. Addition of 5 IU/ml FSH caused a dose
      dependent and reversible depolarization of the resting membrane potential by
      +15.3 +/- 1.0 mV accompanied by a decrease of the input resistance. The
      depolarization was completely abolished in chloride-free solutions. The reversal
      potential of the effect was close to the calculated reversal potential for
      chloride. We conclude that FSH activates a chloride conductance in cultured TM4
      Sertoli cells.

PMID- 9144424
TI  - Inhibition by 2-arachidonoylglycerol, a novel type of possible neuromodulator, of
      the depolarization-induced increase in intracellular free calcium in
      neuroblastoma x glioma hybrid NG108-15 cells.
AB  - 2-Arachidonoylglycerol was found to inhibit the depolarization-induced increase
      in [Ca2+]i in NG108-15 cells differentiated with prostaglandin E1 and
      theophylline in a dose-dependent manner. Such an effect appears to be rather
      specific to polyunsaturated fatty acid-containing monoacylglycerols such as 2
      arachidonoylglycerol. Neither 2-palmitoylglycerol nor free arachidonic acid
      exhibited appreciable inhibitory activity. These observations raise the
      possibility that 2-arachidonoylglycerol attenuates the increase in [Ca2+]i,
      thereby modulating several neural functions in this type of cell.

PMID- 9144425
TI  - Synthesis and cytotoxic studies of 5-O-(beta-glucopyranosyl)-2-nitrobenzyl caged
      L-leucyl-L-leucine methyl ester with increased solubility in PBS containing 1%
      DMSO.
AB  - We report the synthesis of a new type of a caged L-leucyl-L-leucine methyl ester,
      a sugar derivative 2, and study its photochemical and immunological properties.
      Compared with those of the previously reported o-nitrobenzyl caged compound, 1,
      and another new 4, 5-dimethoxy-2-nitorobenzyl caged compound 3, 2 was found to be
      almost 30 times more soluble in PBS containing 1% DMSO, and released leucyl
      leucine methyl ester upon irradiation more efficiently than 1. Efficiency of
      induction of apoptosis of HL60 cells by irradiation of a solution containing 2
      was only slightly lower than that by leucyl-leucine methyl ester itself.

PMID- 9144426
TI  - Abrogation of G1 arrest after DNA damage is associated with constitutive
      overexpression of Mdm2, Cdk4, and Irf1 mRNAs in the BALB/c 3T3 A31 variant 1-1
      clone.
AB  - A search of cell lines showing aberrant cell-cycle checkpoints revealed the lack
      of gamma-irradiation-induced G1 arrest in the BALB/c 3T3 A31 variant 1-1 (A31-1
      1) clone. This clone is well-known for its hypersensitivity to transformation by
      DNA damaging agents. p53 stabilization and p21 mRNA induction after 8 Gy
      irradiation were observed, suggesting that the abrogation of G1 arrest occurred
      in spite of normal p53 and p21 responses by abnormal regulation of other cellular
      factors. Constitutive overexpression of Mdm2 and Cdk4 mRNAs was found, which
      might have contributed to the loss of G1 arrest. In addition, overexpression of a
      growth-suppressive transcription factor, Irf1, a putative key molecule in the p53
      independent pathway after DNA damage, was also observed, although the relation to
      the loss of G1 arrest could not be elucidated.

PMID- 9144427
TI  - Promoter-dependent tissue-specific expressive nature of imprinting gene, insulin
      like growth factor II, in human tissues.
AB  - The insulin-like growth factor II (IGF2) is a polypeptide with structure homology
      to insulin which possesses mitogen activity, and imprinted with paternal allele.
      In order to elucidate the distribution of imprinting pattern and relationship
      between allele- and tissue-specific expression of IGF2 in growth and maturation
      of human tissues, we investigated allele-specific expression of IGF2 in a wide
      spectrum of normal maturated human tissues by a PCR-based assay and found
      monoallelic expression in all eight-type tissues tested except human adult liver.
      Moreover, when a RT-PCR based sensitive allele-specific primer extension for an
      Apa I polymorphism within exon 9 of IGF2 was used, the analysis revealed the gene
      was normally imprinted in placenta; in contrast to the finding with placenta,
      IGF2 transcripts were biallelically expressed in human adult liver. Our results
      have clearly demonstrated preferential paternal expression and tissue-specific
      imprinting pattern of IGF2 in all human tissues tested in this study.
      Collectively, since IGF2 expression in developing fetal and adult liver is
      specified by distinct promoters, these extensive observations definitively
      indicate that transcriptional imprinting of IGF2 is more likely a promoter
      dependent manner.

PMID- 9144428
TI  - Ontogeny of glutamic acid decarboxylase gene expression in the mouse pancreas.
AB  - Using two RT-PCR quantitative assays, we measured the pancreatic expression of
      the two isoforms of glutamic acid decarboxylase in the foetus, newborn and 14-,
      21- and 35-day-old male and female NOD and C57BL/6 mice. In the C57BL/6 mouse,
      GAD 67 pancreatic expression is stable; in NOD mice, GAD 67 expression is similar
      to that found in control mice, except at 5 weeks of age, when pancreatic GAD 67
      expression is about 2.5 times higher than in C57BL/6 mice. The pancreatic
      expression of GAD 65 is under the detection limit of the assay until 5 weeks of
      age. The overexpression of GAD 67 characterized in pancreas from 5-week-old NOD
      mice could be the result of beta cell hyperactivity, previously reported in this
      mouse strain.

PMID- 9144429
TI  - Interleukin-15 promotes angiogenesis in vivo.
AB  - IL-15, a cytokine with biological functions on cells of lymphoid lineage similar
      to those of IL-2, mediates its activities through the beta and gamma chains of
      the IL-2/15R and its own alpha chain. Unlike IL-2, IL-15 also binds to
      endothelial cells with high affinity. We report here that IL-15 is a stimulator
      of angiogenesis in vivo. When injected subcutaneously into nude mice, IL-15
      consistently induced neovascularization of Matrigel plugs. Endothelial cells were
      found to express the IL-15R alpha chain and the IL-2/15R beta and common gamma
      chains. IL-15 induced the rapid tyrosine phosphorylation of proteins in
      endothelial cells, but did not stimulate endothelial cell proliferation in vitro.
      These findings document a previously unrecognized biological property of IL-15
      and emphasize the role of IL-15 as an important mediator outside the immune
      system.

PMID- 9144430
TI  - A radiobiological probe for simultaneous NMR spectroscopy and 192Ir gamma
      irradiation of Saccharomyces cerevisiae.
AB  - A novel nuclear magnetic resonance (NMR) spectroscopy probe was designed and
      constructed for the study of transient metabolic changes in cellular systems
      during exposure to ionizing radiation. The probe incorporated a bioreactor, a
      radiation source, and a radiofrequency detection circuit tunable between 100 and
      300 MHz for in vivo NMR spectroscopy of 23Na, 13C, and 31P at 11.7 Tesla. The
      bioreactor system allowed perfusion, oxygenation, and temperature control of
      cultured cells during irradiation and while performing simultaneous spectroscopic
      experiments. The concentric design of the bioreactor allowed for the insertion of
      a 192Ir gamma ray source (E(gamma) = 370 keV) to allow irradiation of the
      bioreactor system during the acquisition of NMR spectra. Initial results of 31P
      spectra obtained during simultaneous gamma irradiation of Saccharomyces
      cerevisiae at approximately 8 Gy/hr show rapid decreases in adenosine
      triphosphate (ATP) and polyphosphate at the onset of irradiation followed by a
      slow recovery of polyphosphate.

PMID- 9144431
TI  - Sodium-dependent and -independent transport of L-glutamate in the rat intestinal
      crypt-like cell line IEC-17.
AB  - Mechanisms of L-glutamate transport in intestinal crypts were investigated using
      the rat intestinal crypt-like cell line IEC-17. Kinetic analysis and competition
      experiments run in the presence or in the absence of extracellular sodium
      indicate that L-glutamate uptake occurs through three different transport
      components: (1) a high affinity Na+-independent component also carrying cystine,
      similar to system x(c)-; (2) a high affinity Na+-dependent component inhibited by
      D- and L-aspartate corresponding to the ubiquitous system X(A,G)-; and (3) a low
      affinity Na+-dependent system resembling the neutral amino acid transport system
      ASC. The simultaneous presence of these three components suggest that crypt cells
      are ready to face potential high variations of L-glutamate concentration in the
      intestinal villus environment.

PMID- 9144432
TI  - Amino acid variants in the human leptin receptor: lack of association to juvenile
      onset obesity.
AB  - The recently described putative lipostat system mediated in part by leptin and
      its hypothalamic receptor provides logical candidate genes for the molecular
      basis of inherited obesity in humans on the basis of the occurrence of profound
      obesity observed in obese and diabetic mice, in which the genes for leptin or its
      receptor, respectively, are mutated. In this study we tested the hypothesis that
      juvenile onset obesity in humans may be caused by leptin resistance mediated
      through genetic variations in isoforms of the hypothalamic leptin receptor. One
      hundred and fifty-six obese Danish men with a history of juvenile onset obesity
      were selected at the draft board examination with a body mass index (BMI) > or =
      31 kg/m2. From the same study population a control group of 205 control subjects
      (mean BMI = 21,5 kg/m2) were randomly selected. Single strand conformational
      polymorphism scanning of genomic DNA from 56 obese subjects revealed a total of
      four amino acid variants located in coding exons 2, (Lys109Arg), 4 (Lys204Arg and
      Gln223Arg), and 12 (Lys656Asn), respectively. The codons 109, 223, and 656
      variants were common, but their prevalence was not significantly different
      between obese and lean carriers with regard to allele or carrier frequency (p >
      0.1 in each case). The codon 204 mutation was only found in one obese subject. In
      conclusion, it is unlikely that mutations in the coding region of the long
      isoform of the leptin receptor are a common cause of juvenile onset obesity.

PMID- 9144433
TI  - Studies on the intracellular localization of acetyl-CoA carboxylase.
AB  - The present work was performed to identify the subcellular localization of
      hepatic acetyl-CoA carboxylase (ACC). Cellular organelles involved in fatty acid
      oxidation that contain a malonyl-CoA sensitive carnitine palmitoyltransferase
      (CPT) activity or that are linked to the control of this activity were analysed
      for the presence of ACC. No significant amount of ACC was observed in the
      mitochondrial fraction prepared from isolated rat hepatocytes. Furthermore, no
      association of ACC activity and mass with isolated hepatic peroxisomes could be
      detected. Incubation of isolated hepatocytes with compounds known to affect the
      integrity of the cytoskeleton like okadaic acid or taxol indicates that ACC is
      associated with this subcellular structure of the hepatocyte. Such association
      may allow for efficient regulation of CPT activity and thus of fatty acid
      oxidation.

PMID- 9144434
TI  - cDNA cloning and tissue-specific expression of a novel basic helix-loop-helix/PAS
      protein (BMAL1) and identification of alternatively spliced variants with
      alternative translation initiation site usage.
AB  - Basic helix-loop-helix (bHLH)/PAS proteins, such as Sim, act as transcriptional
      factors, playing a critical role in the control of central nervous system (CNS)
      development. To isolate novel bHLH/PAS factors in the CNS an iterative search of
      a database for expressed sequence tags (ESTs) resulted in the location of several
      bHLH/PAS protein-like sequences. The rapid amplification of cDNA end (RACE)
      method was applied to isolate full-length cDNAs of these ESTs. Several 5' and 3'
      terminal sequences were isolated using primers derived from an EST from the human
      brain cDNA library. The predicted novel factor polypeptide had bHLH and PAS
      domains that were highly homologous with those of Ah receptor nuclear
      translocator (Arnt) and Arnt2. Combination of the isolated cDNA fragments
      revealed the existence of several alternatively spliced variants. The
      distribution of the novel bHLH/PAS factor message was analyzed by Northern blot
      hybridization. This detected only one transcript, which was 2.9 kb in size.
      Strong hybridization was found in the brain, skeletal muscle and heart.
      Expression of the novel bHLH/PAS factor, brain and muscle Arnt-like protein 1
      (BMAL1), was different from that of Arnt and Arnt2, suggesting that BMAL1 has a
      different function in the CNS and muscle than Arnt and Arnt2.

PMID- 9144435
TI  - The Xanthomonas campestris gumD gene required for synthesis of xanthan gum is
      involved in normal pigmentation and virulence in causing black rot.
AB  - A cloned 4.1-kb EcoRI fragment from Xanthomonas campestris pv. campestris was
      previously shown to complement the non-mucoid mutant P22 and increase xanthan gum
      production after being transformed into the wild-type strain Xc17. The gene
      responsible for these effects was identified, sequenced, and shown to be the gumD
      gene which has previously been proposed to encode glucose transferase activity,
      an enzyme required for adding the first glucose residue to the isoprenoid
      glycosyl carrier lipid during xanthan synthesis. A gumD mutant, isolated from
      Xc17 by gene replacement, was shown to possess altered pigment xanthomonadin
      profiles and exhibit reduced virulence in causing black rot in broccoli. This
      study appears to be the first to demonstrate that interruption of a gene required
      for xanthan synthesis can lead to reduced virulence of X. campestris.

PMID- 9144436
TI  - Cytotoxic effect of cytokines on murine colon carcinoma cells involves TNF
      mediated apoptosis.
AB  - We have studied the cytotoxic effect of TNF-alpha on C-26 murine colon carcinoma
      cells in vitro. Treatment with TNF-alpha alone did not result in any demonstrable
      cytotoxicity. However, when combined with IFN-gamma, the cytotoxic effect of TNF
      alpha was enhanced in a dose-dependent manner. An agonistic TNF-R1 specific
      antibody and recombinant human TNF-alpha both exerted a cytotoxic effect when
      combined with IFN-gamma, suggesting that the cytotoxicity was mediated through
      the TNF-R1. The cytotoxicity was associated with production of nitric oxide
      without any direct involvement in the cytotoxic effect. At the ultrastructural
      level, treated cells displayed a typical apoptotic morphology which was not
      accompanied by internucleosomal cleavage of DNA as shown by conventional
      electrophoresis.

PMID- 9144437
TI  - Nitric oxide synthase mRNA expression in human fetal membranes: a possible role
      in parturition.
AB  - Nitric oxide (NO) is a potent endogenous smooth-muscle relaxant. It is
      synthesised from 1-arginine by isoforms of nitric oxide synthase (NOS). Whilst it
      is clear that the uterus responds to NO by relaxation, NOS expression has not
      been investigated in fetal membranes or myometrium in human pregnancy. This study
      has shown, using semi-quantitative RT-PCR, expression of cNOS mRNA in human
      amnion, chorion-decidua, and placenta. iNOS mRNA expression was demonstrated in
      human amnion, chorion-decidua, and placenta. It is possible that NO synthesised
      in fetal membranes may act either directly to inhibit myometrial contractility or
      indirectly to interact with other labour-associated genes, such as cyclo
      oxygenase, to coordinate the onset of labour.

PMID- 9144438
TI  - A 70-kDa protein facilitates interleukin-4 signal transduction in the absence of
      the common gamma receptor chain.
AB  - Interleukin-4 signal transduction (and activation of STAT 6) is known to be
      mediated via its binding to a p140 receptor chain and the common gamma chain
      (gamma c). In non-activated monocytes, neither the gamma c nor its associated
      signal transducing molecule, Jak3, is expressed. We nevertheless show that IL-4
      can initiate the tyrosine phosphorylation and DNA binding of STAT 6 in these
      cells. We present evidence for an additional 70 kDa IL-4 receptor chain which
      mediates the tyrosine phosphorylation of STAT 6 via Jak2, and suggest that this
      is the means by which IL-4 can signal in cells lacking the gamma c.

PMID- 9144439
TI  - Insulin gene region contributes to genetic susceptibility to, but may not to low
      incidence of, insulin-dependent diabetes mellitus in Japanese.
AB  - In the Caucasian population, it has been demonstrated that the insulin gene (INS)
      region contains the insulin-dependent diabetes mellitus locus (IDDM2). In the
      Japanese population, however, there has been no report demonstrating the
      contribution of IDDM2 to the pathogenesis of IDDM. We conducted an association
      study of IDDM in a large number of Japanese subjects with multiple polymorphisms
      in INS region. We found a significant association of the INS region with IDDM.
      Alleles positively associated with IDDM in INS region were the same as those
      positively-associated with IDDM in Caucasian population, although positively
      associated alleles are very common (allele frequencies > 0.9) in the Japanese
      general population. These data suggest that IDDM2 is involved in the genetic
      susceptibility to IDDM in Japanese. The high frequencies of disease-associated
      alleles in the general population suggest that IDDM2 locus is not responsible for
      the low incidence of IDDM in Japanese.

PMID- 9144440
TI  - Generation of the replication-competent human immunodeficiency virus type 1 which
      expresses a jellyfish green fluorescent protein.
AB  - The gene encoding a red-shifted green fluorescent protein variant (EGFP) was
      introduced into a human immunodeficiency virus type 1 (HIV-1) molecular clone by
      replacing the nef gene. The EGFP-expressing HIV-1 replicated efficiently in
      established human T cells. The expression of EGFP in the virus-infected cells was
      confirmed by fluorescence microscopy and also by Western blot analysis using the
      GFP antibodies. The EGFP gene was stably maintained in the viral genome during
      prolonged passages. EGFP-expressing HIV-1 could be used for anti-HIV-1 drug
      screening, sorting of virus-infected cells by fluorescence activated cell sorting
      (FACS) analysis, and for the rapid and simple detection of virus-infected cells
      by fluorescence microscopy.

PMID- 9144441
TI  - Mechanism of calcium entry during axon injury and degeneration.
AB  - Axon degeneration is a hallmark consequence of chemical neurotoxicant exposure
      (e.g., acrylamide), mechanical trauma (e.g., nerve transection, spinal cord
      contusion), deficient perfusion (e.g., ischemia, hypoxia), and inherited
      neuropathies (e.g., infantile neuroaxonal dystrophy). Regardless of the
      initiating event, degeneration in the PNS and CNS progresses according to a
      characteristic sequence of morphological changes. These shared neuropathologic
      features suggest that subsequent degeneration, although induced by different
      injury modalities, might evolve via a common mechanism. Studies conducted over
      the past two decades indicate that Ca2+ accumulation in injured axons has
      significant neuropathic implications and is a potentially unifying mechanistic
      event. However, the route of Ca2+ entry and the involvement of other relevant
      ions (Na+, K+) have not been adequately defined. In this overview, we discuss
      evidence for reverse operation of the Na+-Ca2+ exchanger as a primary route of
      Ca2+ entry during axon injury. We propose that diverse injury processes (e.g.,
      axotomy, ischemia, trauma) which culminate in axon degeneration cause an increase
      in intraaxonal Na+ in conjunction with a loss of K+ and axolemmal depolarization.
      These conditions favor reverse Na+-Ca2+ exchange operation which promotes
      damaging extraaxonal Ca2+ entry and subsequent Ca2+-mediated axon degeneration.
      Deciphering the route of axonal Ca2+ entry is a fundamental step in understanding
      the pathophysiologic processes induced by chemical neurotoxicants and other types
      of nerve damage. Moreover, the molecular mechanism of Ca2+ entry can be used as a
      target for the development of efficacious pharmacotherapies that might be useful
      in preventing or limiting irreversible axon injury.

PMID- 9144442
TI  - Demonstration of a cellular immune response in halothane-exposed guinea pigs.
AB  - Halothane hepatitis is considered to be a result of an idiosyncratic autoimmune
      reaction brought about by the formation of neoantigens that have been generated
      by covalent binding of halothane biotransformation intermediates. The guinea pig
      is being examined as an animal model to investigate an immune-mediated mechanism
      for halothane hepatotoxicity. Male Hartley guinea pigs were exposed to 1%
      halothane/40% oxygen for 4 hr, three times with 40-day intervals. Kupffer cells
      and splenocytes were isolated from animals on various days after each halothane
      exposure. Splenocytes were cocultured in a lymphocyte transformation test with
      various concentrations of TFA(trifluoroacetylated)-antigens for 7 days and
      proliferation was measured by 3H-thymidine incorporation. In a second experiment,
      Kupffer cells were cocultured with autologous as well as allogeneic splenocytes
      with or without concanavalin A to determine whole cell sensitization and
      accessory function by Kupffer cells from treated animals. A 4-fold increase in
      splenocyte proliferation occurred in response to TFA-guinea pig albumin. No
      significant increase in proliferation could be detected with TFA-lysine or guinea
      pig albumin. A 14-fold increase in splenocyte proliferation also occurred in
      response to Kupffer cells from halothane-exposed animals. Autologous splenocytes
      demonstrated more of a response from treated versus control animals, indicating
      possible involvement of major histocompatibility complex II antigens. These
      results indicate recognition of TFA-antigens and Kupffer cells as antigen
      presenting cells in halothane-exposed guinea pigs. This study provides good
      evidence that a cellular immune response is involved in the guinea pig after
      halothane exposure.

PMID- 9144443
TI  - Correlation of 2,3,7,8-tetrachlorodibenzo-p-dioxin induction of cytochrome P4501A
      in vascular endothelium with toxicity in early life stages of lake trout.
AB  - Edema and cardiovascular dysfunction occur in vertebrates exposed to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) during early development. This study examined
      cytochrome P4501A (CYP1A) induction in endothelium and its possible association
      with mortality due to the edema and vascular effects of TCDD in lake trout early
      life stages. Lake trout (Salvelinus namaycush) eggs were injected at 24-50 hr
      postfertilization with 0.2 microl of 50 mM phosphatidylcholine liposomes or
      liposomes containing TCDD to give seven doses ranging from 11 to 176 pg TCDD/g
      egg. Doses of TCDD greater than 44 pg/g egg elicited hemorrhages; yolk sac,
      pericardial, and meningial edema; craniofacial malformations; regional ischemia;
      growth retardation; and mortality at the sac fry stage of development. Expression
      of CYP1A was assessed at four developmental stages, by immunohistochemical
      analysis of serial sections of individual fish with monoclonal antibody 1-12-3 to
      teleost CYP1A. CYP1A staining occurred in endothelial cells of many organs of
      TCDD-exposed but not vehicle-exposed embryos at 1 week prehatch and sac fry at 2
      weeks posthatch. Earlier developmental stages examined were negative for CYP1A
      expression at any dose of TCDD. The strongest response occurred in sac fry at
      TCDD doses greater than 88 pg TCDD/g egg but was detected at doses as low as 22
      pg TCDD/g egg. CYP1A staining in endothelium appeared at lower doses and was
      stronger than that in other cell types, in both prehatch embryos and posthatch
      sac fry. Thus, the vascular system is a major initial site affected by TCDD in
      lake trout early life stages, and the vascular endothelium is a cell type
      uniquely sensitive to induction of CYP1A in these developing animals. Based on an
      index of immunohistochemical staining of CYP1A, endothelial CYP1A induction in
      sac fry by TCDD occurred with an ED50 of 64-69 pg TCDD/g egg, similar to the dose
      response for mortality occurring during the sac fry stage of development (LD50 =
      47 pg TCDD/g egg). The correlations seen here suggest that CYP1A or aryl
      hydrocarbon receptor (AhR) in the endothelium may be linked to early lesions that
      result in TCDD-induced vascular derangements leading to yolk sac, pericardial,
      and meningial edema that is associated with lake trout sac fry mortality, but the
      precise mechanism remains to be determined.

PMID- 9144444
TI  - Detoxification of mercury by selenium by binding of equimolar Hg-Se complex to a
      specific plasma protein.
AB  - Toxicity of mercury (Hg) can be reduced by coadministration with selenium (Se),
      and this has been explained by the formation of a complex between a specific
      plasma protein and the two elements, which are bound to the protein at an
      equimolar ratio. The purpose of the present study was to characterize the
      specific binding protein in order to clarify the detoxification mechanism. The
      coadministration of 82Se-enriched selenite and mercuric chloride into a rat
      produced a 82Se- and Hg-binding peak on a gel filtration column as measured by
      high-performance liquid chromatography with detection by inductively coupled
      argon plasma-mass spectrometry (ICP-MS). The specific binding protein was also
      detected in vitro by incubating 82Se-enriched selenite and mercuric chloride in
      serum in the presence of glutathione. The molar ratio of Se/Hg = 1 was maintained
      in binding not only to the specific protein but also to other proteins under any
      condition. In in vitro experiments, it was shown that although the two elements
      could bind to many plasma proteins, the affinity to the specific protein was
      extremely high and it showed a binding capacity of 500 nmol Hg or Se/the specific
      protein in 1 ml of serum. These results suggest that the two elements form an
      equimolar complex at first and then bind specifically to the protein. Further,
      the binding of the two elements to the protein was inhibited by the addition of
      polylysine to the reaction mixture, suggesting that the two elements interact
      with the protein through basic amino acids in the molecule and also that the
      protein may be one of the heparin-binding proteins since the heparin-binding
      sites mainly consist of basic amino acids.

PMID- 9144445
TI  - Pharmacologic modulation of reduced glutathione circadian rhythms with buthionine
      sulfoximine: relationship with cisplatin toxicity in mice.
AB  - The relationship between the rhythm in reduced glutathione (GSH) and that in
      cisplatin (CDDP) toxicity was investigated in a total of 560 male B6D2F1 mice,
      using buthionine sulfoximine (BSO). GSH was measured by high-performance liquid
      chromatography (HPLC) in four tissues, at each of six sampling times, 4 hr apart.
      A significant 24-hr rhythm was statistically validated in liver, jejunum, and
      colon, but not in bone marrow. Relative to liver, glutathione content was 56% in
      colon, 38% in bone marrow, 25% in jejunum, and negligible in kidney, where
      cysteine, a final product of GSH catabolism, displayed a 12-hr rhythmic
      variation. This rhythm may reflect that in the activity of GSH-degrading enzymes.
      BSO (450 mg/kg ip, 4 hr before sampling) reduced liver GSH threefold and kidney
      cysteine content was halved, but this pretreatment had no significant effect upon
      GSH content in the other organs. Furthermore, the period of the physiologic liver
      GSH rhythm changed from 24 hr to a composite (24 + 12 hr) period. This change in
      the period may result from an unmasking of the 12-hr rhythm in GSH-degrading
      enzyme activity by GSH synthesis blockade. Maximal values occurred in the mid
      rest span and in the mid-active span after BSO administration. In the other
      tissues, the 24-hr period remained unchanged. BSO injection largely enhanced CDDP
      toxicity (as assessed by survival, leukopenia, and histologic lesions in kidney
      and bone marrow) and kidney mean platinum concentration. Furthermore, BSO
      pretreatment modified the period of CDDP toxicity rhythm: survival followed a
      significant 12-hr-rhythm, instead of a 24-hr rhythm. The cycling of GSH
      concentration results from a balance between synthesis and catabolism and likely
      constitutes one of the main components of the circadian rhythm in CDDP toxicity
      in mice.

PMID- 9144446
TI  - Confocal microscopic characterization of initial corneal changes of surfactant
      induced eye irritation in the rabbit.
AB  - We have previously demonstrated with slightly and severely irritating surfactants
      that the new technology of noninvasive, in vivo confocal microscopy (CM) can be a
      useful approach to a better understanding of the pathobiology of ocular
      irritation in situ. In this study, in vivo CM was used to qualitatively and
      quantitatively characterize the initial microscopic corneal changes occurring
      with surfactants of slight, mild, moderate, and severe irritation. Surfactants
      were directly applied to the corneas of rabbits (6/group) at a dose of 10 microl.
      Eyes and eyelids were examined macroscopically and scored for irritation
      beginning at 3 hr after dosing and periodically through Day 35. Concurrently, the
      corneas were evaluated by in vivo CM; 3D data sets extending from the surface
      epithelium to the endothelium were assessed for surface epithelial cell size,
      epithelial layer thickness, total corneal thickness, and depth of keratocyte
      necrosis. The average macroscopic scores at 3 hr for the slight, mild, moderate,
      and severe irritants were 6.0, 39.3, 48.5, and 68.7, respectively, of a possible
      110. At 3 hr, in vivo CM revealed corneal injury with the slight irritant limited
      to the epithelium, resulting in reductions in epithelial cell size and thickness
      to 59.0 and 82.4% of controls (p < 0.001 and p < 0.01, respectively). These
      parameters returned to normal by Day 3. For the mild irritant, at 3 hr the
      epithelium was absent, corneal thickness was increased to 157.6% of controls (p <
      0.001), and necrosis of keratocytes extended to an average depth of 4.3 microm
      (0.8% of the corneal thickness); these parameters were essentially normal by Day
      14. For the moderate irritant, at 3 hr the epithelium was markedly attenuated,
      corneal thickness was increased to 155.8% of controls (p < 0.001), and keratocyte
      necrosis extended to an average depth of 19.0 microm (3.6% of corneal thickness;
      statistically greater than with the mild irritant, p < 0.001); these parameters
      were essentially normal by Day 14. For the severe irritant, at 3 hr the
      epithelium was significantly thinned, corneal thickness was increased to 165.9%
      of controls (p < 0.001), and keratocyte necrosis occurred to an average depth of
      391.1 microm (70.1% of corneal thickness). These findings demonstrate that
      significant differences in area and depth of injury occur with surfactants of
      differing irritancy. The data suggest that differences at 3 hr can be used to
      distinguish different levels of ocular irritation. Data such as these will be
      important in the development and evaluation of future mechanistically based in
      vitro alternatives for ocular irritancy testing.

PMID- 9144447
TI  - Methyl tert-butyl ether causes alpha2u-globulin nephropathy and enhanced renal
      cell proliferation in male Fischer-344 rats.
AB  - Methyl tert-butyl ether (MTBE), a fuel additive blended into unleaded gasoline to
      decrease carbon monoxide emissions, induces renal tumors in male, but not female,
      rats exposed by inhalation to > or =3000 ppm MTBE. A number of chemicals that
      induce male rat-specific renal tumors also cause a syndrome unique to male rats
      referred to as alpha2u-globulin nephropathy (alpha2u-N). The objective of the
      present study was to determine if MTBE induces an alpha2u-N and renal cell
      proliferation in male F-344 rats. Male and female F-344 rats were exposed to MTBE
      vapors of 0, 413, 1516, or 3013 ppm for 6 hr/day for 10 consecutive days.
      Significant proximal tubule necrosis and protein droplet accumulation were
      observed in kidneys from male rats exposed to 1516 and 3013 ppm MTBE.
      Significantly greater labeling indices were observed in all groups of MTBE
      exposed male rats. alpha2u-Globulin immunoreactivity was present in and confined
      to protein droplets in male rat kidney. A mild dose-related increase in alpha2u
      concentration in the kidney, as measured by an enzyme-linked immunosorbent assay,
      was observed in male rats exposed to MTBE, with a statistically significant
      increase in alpha2u concentration in male rats exposed to 3013 ppm MTBE. There
      was a strong positive correlation (r = 0.994) with exposure concentration between
      cell proliferation and alpha2u concentration in male rat kidney. No significant
      differences were observed in female rats for any of these responses. Further
      analysis of kidney cytosol failed to demonstrate the accumulation of any protein
      besides alpha2u in MTBE-exposed male rat kidney. These findings demonstrate that
      MTBE causes a mild induction of alpha2u-N and enhanced renal cell proliferation
      in male, but not female, F-344 rats, suggesting a role for alpha2u-N in renal
      tumorigenesis.

PMID- 9144449
TI  - Production and characterization of specific antibodies: utilization to predict
      organ- and species-selective pneumotoxicity of 3-methylindole.
AB  - 3-Methylindole (3MI) selectively causes damage to pulmonary tissues; the species
      selective order is goats, rats, and rabbits, with rabbits sustaining the least
      damage. 3MI is bioactivated to toxic intermediates by cytochrome P450 enzymes.
      Covalent binding of the electrophilic 3-methyleneindolenine intermediate to
      proteins is a likely mechanism of 3MI-mediated lung damage. Polyclonal antibodies
      were developed to thioether adducts of 3-methyleneindolenine and were shown by
      competitive enzyme-linked immunosorbent assay (ELISA) to be highly selective for
      the detection of 3MI adducts. Rabbits, rats, and goats were treated with 350,
      400, and 15 mg/kg 3MI, respectively. The lungs, liver, and kidneys of each animal
      were collected 24 hr later and tissue fractions were analyzed by ELISA. Lung
      tissue fractions from goat (pellet, cytosol, and microsomes) had greater
      immunoreactivity than those from rat. Immunoreactivity in rat tissues was greater
      than that in rabbit tissues. In all of the animals, lung had greater
      immunoreactivity than kidney, and kidney had greater reactivity than liver. These
      studies demonstrate that thioether adducts of 3MI with proteins can be detected
      specifically by these antisera, and the adducts are precisely correlated to
      species and tissue susceptibility of 3MI. In addition, human lung and liver
      samples were moderately immunoreactive. Therefore, humans form adducts of 3MI in
      these tissues and are predicted to be susceptible to 3MI-mediated toxicity.

PMID- 9144448
TI  - Role of CYP3A in ethanol-mediated increases in acetaminophen hepatotoxicity.
AB  - CYP2E is considered the only form of cytochrome P450 responsible for ethanol
      mediated increases in acetaminophen hepatotoxicity. However, in experimental
      systems used for investigating ethanol-mediated increases in acetaminophen
      hepatotoxicity, animals are withdrawn from ethanol for 16 to 24 hr before the
      administration of acetaminophen to ensure the clearance of ethanol from the
      circulation. In rats, CYP2E has been shown to decrease to control levels after
      this time period of withdrawal from ethanol. We have previously shown in cultured
      human and rat hepatocytes, and in intact rats, that ethanol induces CYP3A in
      addition to CYP2E. To determine if there might be a role for CYP3A in ethanol
      mediated APAP hepatotoxicity in addition to the recognized role for CYP2E, we
      investigated the effect of triacetyloleandomycin (TAO) on acetaminophen
      hepatotoxicity in ethanol-pretreated rats, as well as the effect of 11 hr
      withdrawal from ethanol on hepatic levels of CYP3A and CYP2E. TAO was dissolved
      in saline instead of dimethylsulfoxide, the solvent most usually employed, since
      dimethylsulfoxide inhibits CYP2E. Rats were administered 6.3% ethanol as part of
      the Lieber-DeCarli diet for 7 days, followed by replacement of the liquid diet
      with water for 11 hr. This 11-hr withdrawal from ethanol resulted in a decrease
      in hepatic levels of ethanol-induced CYP2E; however, considerable induction was
      still evident. There was no significant decrease in CYP3A. TAO completely
      prevented the histologically observed liver damage from acetaminophen in ethanol
      pretreated rats, but did not prevent the increase in serum levels of AST. In
      ethanol-pretreated rats, exposure to APAP in the absence of TAO was associated
      with a 75% decrease in CYP3A, compared to animals exposed to APAP in the presence
      of TAO. These results suggest that CYP3A may have been suicidally inactivated by
      acetaminophen in the absence of TAO. Our findings suggest that CYP3A has a major
      role in ethanol-mediated increases in acetaminophen hepatotoxicity.

PMID- 9144450
TI  - Benzoquinone inhibits the voltage-dependent induction of the mitochondrial
      permeability transition caused by redox-cycling naphthoquinones.
AB  - The mitochondrial permeability pore is subject to regulation by a thiol-dependent
      voltage sensor (Petronilli, V., Costantini, P., Scorrano, L., Colonna, R.,
      Passamonti, S., and Bernardi, P., J. Biol. Chem. 269, 16638-16642, 1994); thiol
      oxidation increases the gating potential, which increases the probability of pore
      opening. Monofunctional sulfhydryl-alkylating agents, by preventing formation of
      the disulfide, inhibit oxidant-induced changes in the gating potential. According
      to this paradigm, redox-cycling and arylating quinones should have distinct and
      opposing effects on the voltage-dependent permeabilization of mitochondrial
      membranes. Freshly isolated rat liver mitochondria were susceptible to a calcium
      dependent permeability transition characterized by osmotic swelling and membrane
      depolarization, both of which were inhibited by Cyclosporine A. 1,4
      Naphthoquinone, 2-methyl-1,4-naphthoquinone (menadione), and 2,3-dimethoxy-1,4
      naphthoquinone elicited an increase in gating potential of the permeability pore
      that was prevented by Cyclosporine A or N-ethylmaleimide and reversed by
      dithiothreitol. Benzoquinone, on the other hand, inhibited NADH-ubiquinone
      oxidoreductase. Accordingly, in mitochondria energized with glutamate plus malate
      benzoquinone caused a direct, calcium-independent depolarization of membrane
      potential and mitochondrial swelling that were not inhibited by Cyclosporine A.
      In contrast, benzoquinone did not interfere with succinate-supported
      mitochondrial bioenergetics. In fact, adding benzoquinone to succinate-energized
      mitochondria prevented induction of the mitochondrial permeability transition by
      all three redox-cycling naphthoquinones. We attribute this to the electrophilic,
      sulfhydryl-arylating reactivity of benzoquinone. The results suggest that
      differences in the mechanisms by which quinones of varying chemical reactivity
      interfere with mitochondrial bioenergetics can be explained in terms of the
      distinct manner in which they react with the thiol-dependent voltage sensor of
      the mitochondrial permeability pore.

PMID- 9144451
TI  - Iron deposition at mineralization fronts and osteoid formation following chronic
      cadmium exposure in ovariectomized rats.
AB  - To investigate whether chronic exposure of cadmium (Cd) chloride induces
      osteomalacic lesions similar to Itai-itai disease (IID), ovariectomized rats were
      injected intravenously with the cadmium at doses of 0.05 and 0.5 mg/kg/day, 5
      days per week, for 50 weeks. In six rats in the 0.5 mg/kg group, the
      administration was continued for up to 70 weeks. In the 0.5 mg/kg group, the
      plasma concentration of calcium was similar in the treatment and control groups
      throughout the treatment period. The urinary excretion of calcium increased from
      20 weeks and the increase became marked from 40 weeks. Histopathologically,
      osteoid seams in the femur, tibia, and humerus were increased from 50 weeks, and
      these changes became prominent at 70 weeks. Hypertrophy and hyperplasia of chief
      cells in the parathyroid were also observed from 50 weeks. The osteoid
      morphometry of the trabecular bone of the femur and sternum revealed a dose
      dependent increase in osteoid/bone volumes. Roentgenographs of the antebrachial
      and metacarpal bones taken at 70 weeks showed so-called paper bone. The bone Cd
      content markedly increased until 25 weeks, but thereafter decreased linearly for
      up to 70 weeks. In contrast to the Cd content, the iron content decreased until
      25 weeks, but thereafter increased until 70 weeks. Undecalcified section of the
      humerus showed the deposition of iron and formation of osteoid at mineralization
      fronts. Our data suggest that osteomalacic lesions were caused by chronic Cd
      intoxication, and that iron, as well as Cd, was involved in osteoid formation.

PMID- 9144452
TI  - P-glycoprotein deficiency in a subpopulation of CF-1 mice enhances avermectin
      induced neurotoxicity.
AB  - A subpopulation of CF-1 mice is unusual in its sensitivity to the avermectins,
      abamectin and ivermectin, with neurotoxicity occurring at 100-fold lower doses
      than in other species and mouse strains. We have shown that the sensitive CF-1
      mice are deficient in P-glycoprotein in the intestinal epithelium and brain
      capillary endothelium, tissues forming the principle barriers for penetration
      into the systemic circulation and central nervous system, respectively.
      Consistent with the role of P-glycoprotein as a barrier to tissue entry, the
      plasma and tissue levels of radiolabeled ivermectin in the sensitive mice were
      markedly higher than in the insensitive mice, particularly in brain, the target
      organ for toxicity. Insensitive CF-1 and CD-1 mice showed abundant levels of P
      glycoprotein in these tissues and tolerated doses of abamectin at least 50-fold
      the minimum toxic dose in the sensitive subgroup. In view of these findings in CF
      1 mice with both abamectin and the structural analog ivermectin, which is used
      extensively in the treatment of human filariasis with no evidence of
      neurotoxicity, it is likely that this protein, found in human brain endothelium,
      is highly conserved in the human population.

PMID- 9144453
TI  - Reductions in renal mass and the nephropathy induced by mercury.
AB  - The severity of renal injury induced by several graded doses of mercuric chloride
      and the disposition of mercury were evaluated and compared in control,
      uninephrectomized (50% NPX), and 75% nephrectomized (75% NPX) rats in an attempt
      to determine the effect of increased reductions of renal mass on the nephropathy
      induced by inorganic mercury. Consistent with previously published findings,
      proximal tubular necrosis (as assessed histopathologically and by the urinary
      excretion of lactate dehydrogenase (LDH) and total protein) was significantly
      more severe in 50% NPX rats than in control rats 24 hr after the administration
      of any of three lowest (1.0, 1.5, or 1.75 micromol/kg) doses of mercuric chloride
      used in the study. Interestingly, the severity of proximal tubular necrosis in
      the 75% NPX rats was not greater than that in control rats at these same doses.
      The reason for this appeared to be due to decreased renal accumulation of
      mercury, particularly in the renal cortex and outer stripe of the outer medulla.
      At the highest (8.0 micromol/kg) dose of mercuric chloride used, renal tubular
      injury was very extensive in all three groups of rats, with the level of injury
      being greatest in the 50% NPX rats. The injury was so severe in all three groups
      that acute renal failure was induced within the first 24 hr after the injection
      of mercury. An important finding that was made at this dose was that the level of
      blood urea nitrogen (BUN) was significantly greater in the 75% NPX rats than in
      either the 50% NPX or control rats, which indicates that 75% NPX rats may have
      entered into acute renal failure sooner than the 50% NPX or control rats.
      Overall, the findings from the present study indicate that as renal mass is
      reduced to a level at which renal function is not significantly impaired (50%
      NPX), the severity of the nephropathy induced by mercury is increased. By
      contrast, when the reduction of renal mass progresses to a level at which renal
      function begins to become impaired, the level of proximal tubular injury is not
      greatly different from that of animals with two kidneys, especially at low
      nephrotoxic doses of inorganic mercury. In addition, low nephrotoxic doses of
      inorganic mercury do not appear to affect significantly the reduced glomerular
      filtration rate in 75% NPX rats. However, it does appear that 75% NPX rats may be
      at greater risk of entering into acute renal failure at higher toxic doses of
      inorganic mercury than 50% NPX or control rats.

PMID- 9144454
TI  - Vitamin E modulation of hepatic focal lesion growth in mice.
AB  - The effect of DL-alpha-tocopherol acetate (vitamin E) on hepatic focal lesion
      growth in male B6C3F1 mice previously treated with diethylnitrosamine (DEN) was
      investigated. After hepatic focal lesions were formed, mice were placed into one
      of the following dose groups: 0 mg vitamin E/kg NIH-07 diet, 50 mg vitamin E/kg
      NIH-07 diet (control diet), 250 mg vitamin E/kg NIH-07 diet, and 450 mg vitamin
      E/kg NIH-07 diet. Mice were euthanized after either 30 or 60 days of dietary
      treatment. In normal (nonlesion) liver, vitamin E deficiency (0 mg/kg diet)
      increased hepatic DNA synthesis. In addition, vitamin E supplementation (450
      mg/kg diet) decreased the incidence of hepatic apoptosis, while vitamin E
      deficiency (0 mg/kg diet) increased the incidence of hepatic apoptosis. The
      effect of vitamin E-induced lesion growth was examined by measuring the number of
      focal lesions per liver and the relative focal lesion volume. High-dose vitamin E
      supplementation (450 mg/kg diet) appeared to enhance the growth of hepatic focal
      lesions. In particular, basophilic lesions appeared to be the most sensitive to
      high-dose vitamin E modulation (450 mg/kg diet) as evidenced by increased number,
      volume, and labeling index of hepatic focal lesions. Vitamin E deficiency also
      appeared to enhance the growth of hepatic focal lesions, though to a lesser
      extent than vitamin E supplementation (450 mg/kg diet). In the present study,
      both vitamin E supplementation (450 mg/kg diet) and deficiency (0 mg/kg diet)
      appeared to enhance focal lesion growth albeit neither treatment enhanced lesion
      growth as dramatically as known nongenotoxic hepatocarcinogens (e.g.,
      phenobarbital and dieldrin). The data presented here suggest that oxidative
      stress in focal hepatocytes may be a component of the liver tumor promotion
      process.

PMID- 9144455
TI  - Nitrogen dioxide exposure activates gamma-glutamyl transferase gene expression in
      rat lung.
AB  - Exposure to nitrogen dioxide (NO2) has been shown to activate glutathione
      metabolism in lung and lung lavage. Since GGT is a key enzyme in glutathione
      metabolism and we have previously characterized GGT expression in distal lung
      epithelium and in lung surfactant, we examined the NO2 exposed lung for induction
      of gamma-glutamyl transferase (GGT) mRNA, protein, and enzyme activity. We found
      that the GGT gene product is induced in lung by NO2. The GGT mRNA level in lung
      increases 2-fold within 6 hr and 3-fold after 24 hr of exposure to this oxidant
      gas, and this 3-fold elevation persists even after 14 days of exposure. The
      pattern of GGT mRNA expression switches from the single GGT mRNA III transcript
      in the normal lung to the dual expression of GGT mRNA I and mRNA III. Enzyme
      activity in whole lung increases 1.6- to 2.5-fold while extracellular surfactant
      associated GGT activity accumulates 5.5-fold and GGT protein accumulates in lung
      surfactant. Induction of GGT mRNA and protein is evident in cells of the
      bronchioles by in situ hybridization and immunolocalization, respectively. In
      contrast, alveolar type 2 cells lack an in situ hybridization signal and exhibit
      a reduction in the intensity of immunostaining with prolonged exposure. Our
      studies show that NO2 induces GGT mRNA expression, including GGT mRNA1, in lung
      and GGT protein and enzyme activity in lung and lung lavage in response to the
      oxidative stress of NO2 inhalation.

PMID- 9144456
TI  - Induction of apoptosis in human T-cells by organomercuric compounds: a flow
      cytometric analysis.
AB  - Although several lines of investigation demonstrate that many heavy metals are
      cytotoxic to host defense cells, the mechanism of killing is poorly understood.
      The major focus of this investigation was to determine if organic mercuric
      compounds kill human lymphocytes by inducing the cells to undergo apoptosis and
      to evaluate possible flow cytometric systems for assessing cell death. T-cells
      were exposed to 0.6-5 microM MeHgCl, EtHgCl, or PhHgCl for up to 24 hr and then
      analyzed by flow cytometry. Mercury-treated cells exhibited increased Hoechst
      33258 and 33342 fluorescence while maintaining their ability to exclude the vital
      stain 7-AAD. Furthermore, T-cells exposed to mercury exhibited changes in light
      scatter patterns that included decreased forward light scatter and increased side
      scatter. The light scatter and fluorescent changes were consistent with changes
      that cells display during apoptosis. To further evaluate cell death and to
      distinguish between apoptosis and necrosis, merocyanine 540 staining and annexin
      V binding to the plasma membrane as well as DNA fragmentation were assessed.
      Mercury-treated cells exhibited increased merocyanine 540 fluorescence and
      annexin V binding along with changes in nuclear morphology consistent with the
      notion of apoptosis. Conventional agarose gel electrophoresis failed to
      demonstrate low-molecular-weight DNA bands; however, when probed by flow
      cytometry using both nick translation and a modified TUNEL assay, patterns
      consistent with nuclear fragmentation were evident. We noted that the percentage
      of T-cells undergoing apoptosis was dependent upon the amount of serum present in
      the medium; as serum concentrations were increased from 0 to 10%, cell death
      declined. Apoptosis (33%) was observed within 1 hr of exposure to MeHgCl; maximum
      cell death (67%) occurred after 24 hr exposure. Induction of apoptosis was
      dependent on the mercury concentration and independent of the hydrophobicity of
      the mercury ligand. Finally, we assessed mercury-dependent apoptosis in activated
      T-cells. When treated with mitogen, mercury failed to induce apoptosis in these
      cells. Indeed, there was no evidence of either apoptosis nor necrosis in these
      populations. It was concluded that the activation process prevented development
      of a metabolic state that was required for induction of apoptogenic genes.

PMID- 9144457
TI  - Expression of the aryl hydrocarbon receptor (AhR) and AhR nuclear translocator
      during chick cardiogenesis is consistent with 2,3,7,8-tetrachlorodibenzo-p-dioxin
      induced heart defects.
AB  - We examined cardiotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      in the chick embryo and the cardiac expression of transcription factors, the aryl
      hydrocarbon receptor (AhR) which binds TCDD, and its dimer partner, the AhR
      nuclear translocator (Arnt). Chicken eggs were injected with control (triolein)
      or 1.0 pmol TCDD/g egg prior to incubation and collected on Day 10 when
      cardiomorphogenesis is complete. Relative to controls, TCDD increased heart wet
      weight (27.2 +/- 0.5 versus 36.6 +/- 1.3 mg, p < 0.001) and dry weight (2.7 +/-
      0.1 versus 3.1 +/- 0.1 mg, p < 0.01), and tended to increase heart myosin content
      (3.5 +/- 0.6 versus 6.3 +/- 2.5 microg, p < 0.07), suggesting an increase in
      cardiac muscle mass and edema. Histologic and morphometric analyses revealed that
      10/13 TCDD-exposed hearts exhibited enlarged right and left ventricles, thickened
      ventricular septum, and a thinner left ventricular wall with increased
      trabeculation, and 4/13 exhibited ventricular septal defects compared to controls
      (0/23). To evaluate AhR and Arnt expression, untreated chick embryos were
      collected on Days 2.2, 3, 4, 5, and 8 of incubation, preserved in Bouin's
      fixative, sectioned, and stained with AhR and Arnt antibodies. The AhR was
      expressed ubiquitously in cardiac myocytes, while Arnt expression was restricted
      to myocytes overlying developing septa: atrioventricular canal, outflow tract,
      and atrial and ventricular septa. Both proteins were absent from endocardium and
      endocardial-derived mesenchyme. In addition, cardiac expression of an AhR/Arnt
      target, cytochrome P4501A1, was restricted to myocardium coexpressing AhR and
      Arnt. Thus, the spatial and temporal expression of AhR and Arnt suggests that the
      developing myocardium and cardiac septa are potential targets of TCDD-induced
      teratogenicity, and such targets are also consistent with cardiac hypertrophy and
      septal defects observed following TCDD exposure.

PMID- 9144458
TI  - Cytochrome P450 inactivation during reductive metabolism of 1,1-dichloro-2,2,2
      trifluoroethane (HCFC-123) by phenobarbital- and pyridine-induced rat liver
      microsomes.
AB  - The reductive metabolic activation of 1,1-dichloro-2,2,2-trifluoroethane (HCFC
      123), one of the potential substitutes for the ozone-depleting
      chlorofluorocarbons and a close structural analogue of the hepatotoxic anesthetic
      halothane, was investigated in vitro. During incubation of liver microsomes from
      phenobarbital-(PB) or pyridine-induced (PYR) rats with 0-20 mM HCFC-123 under
      anaerobic conditions, a dose- and time-dependent depletion of added exogenous
      glutathione was observed, indicating the formation of reactive metabolites. Under
      similar incubation conditions, except for the absence of glutathione, 1-chloro
      2,2,2-trifluoroethane and 1-chloro-2,2-difluoroethene were detected as products
      of reductive metabolism of HCFC-123, as previously reported for halothane. As
      shown previously in our laboratory for halothane, under these conditions HCFC-
      123 also caused a statistically significant loss of microsomal cytochrome P450
      (P450) as indicated by a decrease of the classical absorption spectrum in the
      presence of CO. Both glutathione depletion and P450 loss were almost completely
      prevented by previous saturation of the incubation mixture with CO and were
      partially prevented by the presence of the free-radical scavenger N-t-butyl-alpha
      phenylnitrone or the carbene trapping agent 2,3-dimethyl-2-butene, suggesting
      that both types of intermediates may be involved. The loss of P450 was associated
      with a quantitatively similar loss of microsomal heme, as measured by the
      pyridine hemochromogen reaction, with PB but not with PYR microsomes. Finally,
      both the P4502E1-specific p-nitrophenol hydroxylase activity in PYR microsomes
      and the P4502B1/2-specific pentoxyresorufin O-depentylase activity in PB
      microsomes were significantly inhibited (58 and 53%, respectively) by prior
      incubation with HCFC-123, suggesting that both isoforms are able to catalyze the
      activation of this halogenated compound. These results indicate that indeed HCFC
      123, like its analogue halothane, is activated reductively to reactive
      metabolites by at least two P450 isoforms, namely P4502E1 and P4502B1/2. These
      metabolites, probably free radicals and/or carbene species, may attack the enzyme
      resulting in modification of the heme group and subsequent loss of catalytic
      activity.

PMID- 9144459
TI  - Ascorbic acid protects guinea pigs from acute aflatoxin toxicity.
AB  - These studies were conducted to investigate whether ascorbic acid protected
      guinea pigs from aflatoxin B1 (AFB1) toxicity. Young guinea pigs, fed either 0
      (AA) or 25 mg (25 AA) or gavaged 300 mg ascorbic acid (300 AA) per day for 21
      days, were gavaged with the LD50 dose of AFB1 on the 22nd day. Seven out of 10
      animals in the AA group died within 72 hr of AFB1 administration. The livers of
      the animals showed regional massive necrosis and multilobular degeneration. There
      was no mortality in the 25 AA group. Their livers, however, showed changes
      similar to those seen in AA group. Serum alanine amino transferase (ALAT) and
      aspartate amino transferase (ASAT) levels were elevated. There was neither
      mortality nor pathological changes in livers in the 300 AA group. Their ALAT and
      ASAT levels were unaffected. In vitro production of AFM1 by liver microsomes
      tended to be higher than that in the other two groups. Three animals saved from
      the 300 AA group and continued with their supplementation were administered a
      second, intraperitoneal (ip) LD50 dose of AFB1 1 month after the first AFB1 dose.
      One animal died. Livers of the animals showed centrilobular degeneration and
      moderate necrosis in scattered hepatocytes. Liver microsomal cytochrome P450 and
      cytosolic glutathione S-transferase (GST) levels and AFM1 production were
      drastically reduced. ALAT and ASAT activities were raised. The results indicated
      that intake of 300 mg of ascorbic acid almost protected the animals from acute
      toxicity of AFB1 when given by gavage, but not when administered as a second dose
      ip.

PMID- 9144460
TI  - The area under the concentration-time curve of all-trans-retinoic acid is the
      most suitable pharmacokinetic correlate to the embryotoxicity of this retinoid in
      the rat.
AB  - Earlier studies with etretinate and its metabolite acitretin suggested that area
      under the concentration-time curve (AUC) is the most suitable pharmacokinetic
      correlate to etretinate-induced teratogenesis. In an attempt to test this
      hypothesis with respect to the embryotoxic effects of all-trans-retinoic acid
      (all-trans-RA), we determined the embryotoxicity and plasma pharmacokinetics of
      all-trans-RA and its metabolites following administration of all-trans-RA to
      Wistar rats on Gestational Day (GD) 9, either subcutaneously (sc; dose levels 1,
      3, or 5 mg/kg body mass) or orally (po; 5 mg/kg body mass). The 5 mg/kg dose of
      all-trans-RA was not embryotoxic when administered orally but led to high rates
      of embryolethality and skeletal defects following sc treatment. Determination of
      retinoids by HPLC showed that all-trans-RA reached similar maximum plasma
      concentrations (C(max)) after both dosing regimens, but its plasma AUC was ca.
      threefold higher after sc injection than po administration due to the slower
      uptake rate of the drug and its limited detoxification via beta-glucuronidation
      following sc injection. Furthermore, retinoid analysis in rat tissues (liver,
      kidney, duodenum, and jejunum), collected 1 hr after sc or po administration of 5
      mg all-trans-RA/kg body mass on GD 9, confirmed that formation of all-trans
      retinoyl-beta-glucuronide was much more extensive after po than after sc
      administration. Finally, linear regression analysis of either C(max). or AUC
      values of all-trans-RA in rat plasma and fetal abnormality rates showed that AUC
      values are better correlated with the embryotoxic outcome than C(max) [AUC-based
      correlation coefficient (r) > 0.90; C(max)-based r < 0.43]. Our findings
      establish the relevance of the AUC of all-trans-RA, and not its C(max), as the
      most appropriate pharmacokinetic marker of embryonic exposure and embryotoxic
      potency of all-trans-RA and stress the importance of the duration of exposure as
      a major determinant of embryotoxic outcome for retinoids.

PMID- 9144461
TI  - Role of Fas ligand (CD95L) in immune escape: the tumor cell strikes back.
AB  - Several different tumor types have recently been shown to express functional Fas
      ligand (FasL), which may represent an additional mechanism of tumor escape.
      However, the in vivo significance of these findings in the context of potent
      adversaries such as activated CTL or NK cells remains to be fully established.
      The potential interactions between tumor cells and the host immune response are
      thus more complex than previously thought; their elucidation will benefit the
      rational design of cancer immunotherapy strategies.

PMID- 9144462
TI  - C1q binds directly and specifically to surface blebs of apoptotic human
      keratinocytes: complement deficiency and systemic lupus erythematosus revisited.
AB  - Complete deficiency of C1q is almost invariably associated with the development
      of systemic lupus erythematosus. It has been suggested that this association may
      result from a generalized failure to clear Ag-Ab complexes. However, it has not
      been demonstrated how such a broad impairment results in this specific and
      consistent autoimmune phenotype, in which photosensitive skin disease is the most
      prominent manifestation. We believe there is another role for the classical
      pathway in maintaining immune tolerance. Surface blebs of apoptotic keratinocytes
      are concentrated sources of autoantigens, and these packages may define a novel
      immune context and challenge self-tolerance if not properly cleared and
      processed. We demonstrate here that when human keratinocytes are rendered
      apoptotic, they also develop the capacity to specifically and directly bind to
      C1q in the absence of Ab. C1q may mediate Ab-independent clearance of apoptotic
      keratinocytes, and prevent immunization with autoantigens of cutaneous origin.

PMID- 9144463
TI  - Differential dependence on target site tissue for gene gun and intramuscular DNA
      immunizations.
AB  - Surgical ablations revealed different dependencies on the injection site tissue
      for i.m. needle and epidermal gene gun DNA immunizations. Excision of an injected
      muscle bundle within 10 min of DNA inoculation did not affect the magnitude or
      longevity of Ag-specific Ab responses. By contrast, biopsy of the skin target
      site up to 24 h after gene gun bombardment completely abrogated the Ab response
      in the majority of mice. The form of a DNA-expressed Ag (membrane bound,
      secreted, or intracellular) did not affect the temporal requirements for the skin
      and muscle target sites. Skin cells, but not muscle cells, were also required for
      DNA-induced CTL. We conclude that transfected cells in gene gun-bombarded skin,
      but not needle-injected muscle, play a central role in DNA-initiated Ab and CTL
      responses.

PMID- 9144464
TI  - Class I- and class II-reactive TCRs coexpressed on CD4+ T cells both trigger
      CD4/CD8-shared and CD4-unique functions.
AB  - CD4+ and CD8+ T cells emerge from thymic selection expressing a TCR restricted by
      MHC class II (TCRII) and MHC class I (TCRI), and upon Ag stimulation develop
      respectively into Th and CTL effector cells. The influence of thymic
      differentiation and antigenic stimulation on the determination of T cell
      functions was studied, with CD4+ T cells expressing a transgenic TCRI that reacts
      with the class I alloantigen H-2K(b) in a CD8-independent fashion. Such T cells
      additionally express a TCR, probably TCRII, in which the transgenic TCR beta
      chain is associated with endogenously rearranged TCR alpha-chains. Upon in vitro
      stimulation with H-2K(b)-expressing cells, both CD8+ and CD4+ transgenic TCR+ T
      cells developed into CTL capable of killing Ag-expressing target cells through a
      perforin-dependent mechanism, and secreted IL-2 and IFN-gamma. Fas ligand
      dependent killing could also be induced in both CD8+ and CD4+ in vitro stimulated
      T cells. The capacity to secrete IL-4 was restricted to the CD4+ T cells,
      however, suggesting that both CD8/CD4-shared and CD4-unique programs can be
      elicited by stimulation of CD4 T cells through a TCRI. Acquisition of CTL
      function was also induced upon class II alloantigen stimulation through the
      endogenously rearranged TCRII, which represents a polyclonal set of TCRs. IL-2,
      IFN-gamma, and after restimulation, IL-4, were also produced. Thus: 1) events
      associated with intrathymic selection influence the gene program activated in
      response to the same TCRI/APC interaction; and 2) CD4+ T cells expressing a TCRI
      and a TCRII can activate the same gene program after engagement of either one of
      these TCRs.

PMID- 9144465
TI  - In vivo migration of dendritic cells differentiated in vitro: a chimpanzee model.
AB  - Dendritic cells with potent Ag-presenting function can be propagated from
      peripheral blood using recombinant cytokines, and these cells have potential
      usefulness as immunotherapeutic agents in the treatment of cancer and other
      disease states. However, it is not known if these in vitro differentiated
      dendritic cells have the capacity to migrate in vivo, especially to T cell areas
      of lymphoid tissue. We have used a fluorescent marker system to track the
      migration of dendritic cells, propagated in vitro from chimpanzee peripheral
      blood, following s.c. injection. We report that injected dendritic cells migrate
      spontaneously and rapidly to draining lymph nodes, where they remain for at least
      5 days. The injected cells interdigitate with T cells in the parafollicular and
      paracortical zones and retain high level expression of CD86, CD40, and MHC class
      II molecules, reflecting a phenotype of potent APC. We conclude that dendritic
      cells differentiated in vitro from peripheral blood and administered s.c. behave
      in a manner very similar to endogenous Langerhans cells. These data provide
      strong experimental support, in a highly relevant large animal model, for the use
      of in vitro differentiated dendritic cells as vehicles for immunotherapy. More
      importantly, they show that the s.c. route of injection delivers these APC to
      sites of T cell activation, a prerequisite for the generation of an effective
      immune response.

PMID- 9144466
TI  - MRC OX-2 defines a novel T cell costimulatory pathway.
AB  - T cell activation requires the engagement of the TCR as well as a second,
      costimulatory signal. In this study, we demonstrate that MRC OX-2 (OX-2) mediates
      a previously unrecognized T cell costimulatory signal leading to enhanced T cell
      proliferation. One extensively studied costimulatory pathway, the B7/CD28
      pathway, delivers its signal when CD28 is engaged by either of two ligands, B7-1
      or B7-2, expressed on APC. Recent data have suggested that an additional ligand
      may exist in this pathway. This possibility prompted us to search previously
      cloned genes with both structural and expression characteristics similar to B7-1
      and B7-2. Our search yielded OX-2, a rat lymphocyte activation marker, as a
      promising candidate gene. We now report that Chinese hamster ovary cell
      transfectants expressing the OX-2 protein can costimulate murine CD4+ T cells to
      proliferate in an Ag-independent fashion using anti-CD3, as well as an Ag
      dependent fashion using peptide. In contrast to B7-1-mediated costimulation, OX-2
      does not result in detectable levels of IL-2, IL-4, or IFN-gamma. In addition, OX
      2 transfectants do not bind the soluble receptor reagents of the B7/CD28 pathway
      (CD28-Ig and CTLA4Ig). Furthermore, OX-2 costimulation is not inhibited by
      CTLA4Ig, as is B7-1-mediated costimulation, but is readily inhibited with an anti
      OX-2 mAb. Thus, OX-2 is a T cell costimulatory ligand that acts through a non
      B7/CD28 pathway, which leads to functionally distinct consequences, as reflected
      by the resulting cytokine profile.

PMID- 9144467
TI  - Human peptide transporter deficiency: importance of HLA-B in the presentation of
      TAP-independent EBV antigens.
AB  - Two siblings with a peptide TAP deficiency were recently described. Despite poor
      cell surface expression of HLA class I molecules, these patients were not
      unusually susceptible to viral infections. The majority of the cell surface
      expressed class I molecules were HLA-B products as assessed by cytofluorometry
      and biochemical analysis. Analysis of two peptides eluted from the class I
      molecules expressed by TAP-deficient EBV B lymphoblastoid cell lines indicated
      that both were derived from cytosolic proteins and presented by HLA-B molecules.
      Peripheral alphabeta CD8+ T cells were present and their TCR repertoire was
      polyclonal. Most of the alphabeta CD8+ T cell clones studied (21 of 22) were
      nonreactive against cells expressing normal levels of the same HLA alleles as
      those of the TAP-deficient patients. However, it was possible to isolate one
      cytotoxic CD8+ alphabeta T cell clone recognizing the EBV protein LMP2 presented
      by HLA-B molecules on TAP-deficient cells. These observations suggest that in the
      TAP-deficient patients, CD8+ alphabeta T cells could mature and be recruited in
      immune responses to mediate HLA class I-restricted cytotoxic defense against
      viral infections. They also strengthen the physiologic importance of a TAP
      independent processing pathway of the LMP2 protein, which was previously shown to
      contain several other TAP-independent epitopes.

PMID- 9144468
TI  - gamma1 heavy chain transgenes are responsive to IFN-gamma repression and CD40
      ligation.
AB  - The cis-acting elements that regulate production of germ-line transcripts from Ig
      heavy chain genes and subsequent switch recombination to those genes are poorly
      defined. We reported that a 17-kb transgene that includes Igamma1, Sgamma1, and
      Cgamma1 is regulated for germ-line transcription like the endogenous gamma1 gene.
      Transcripts from such transgenes are expressed only in B cells treated with both
      LPS and IL-4, and not in B cells treated with LPS alone or in thymocytes or
      nonlymphoid tissues. We have now found that transcripts from these transgenes are
      induced by treatment of transgenic B cells by IL-4 alone. As reported by others,
      IFN-gamma acts to inhibit the IL-4-mediated induction of germ-line transcripts of
      the endogenous gamma1 gene. We have found that LPS-plus IL-4-induced germ-line
      transcription of gamma1 transgenes is likewise inhibited by treatment of B cells
      with IFN-gamma, so the gamma1 gene must include the cis-acting element(s) that
      confers this inhibition. It is also known that CD40 ligation induces a modest
      amount of germ-line transcripts from the endogenous gamma1 gene and synergizes
      with IL-4 to induce large amounts of germ-line transcripts. The gamma1 transgenes
      are likewise induced by CD40 ligation, suggesting that the response element(s)
      for CD40 ligation can be found in the gamma1 gene. The promoter region for the
      germ-line transcripts and the I exon are likely to include some of these cis
      acting elements. A series of transgenic mice with the promoter/Igamma1 region
      conferred low level, lymphoid-specific, RNA expression to a reporter gene,
      including significant expression in thymocytes. However, the promoter/Igamma1
      transgenes were not regulated like the endogenous gamma1 gene, in that
      transcription in splenic B cells was not increased by LPS plus IL-4.

PMID- 9144469
TI  - P-4 and RNKP-7, new granzyme-like serine proteases expressed in activated rat
      lymphocytes.
AB  - Serine proteases (granzymes) in killer lymphocytes are required for lymphocyte
      cytotoxic granules to lyse target cells. Herein we report the development of a 3
      step PCR cloning technique to amplify novel granzyme genes and two new rat
      granzymes are described. Degenerate oligonucleotide primers were designed based
      on sequence motifs selectively expressed in granzymes. These motifs flank "delta"
      regions that are unique for each granzyme. Total RNA of RNK-16 cells or activated
      splenocytes was amplified by reverse transcriptase-PCR to obtain cDNA fragments
      of several new granzymes. Gene-specific primers based on these delta regions were
      then used for 3'-RACE to obtain clones with the 3' gene ends. Reverse (antisense)
      delta-based or active site serine primers were used with a granzyme 5'-UTR primer
      to obtain clones extending to the 5' ends. Using this technique, two new cDNAs,
      RNKP-4 and RNKP-7, which encode granzymes of 248 and 241 amino acids,
      respectively, were cloned from activated lymphocytes. RNKP-4 is likely the rat
      equivalent of mouse granzyme C. RNKP-7 is most closely related to granzymes F and
      G. Modeling of the predicted proteins suggests large/polar P1 (Gln/Asn)
      specificity for RNKP-4 and large/hydrophobic P1 (e.g., Phe) specificity for RNKP
      7. These specific protease activities were found in cytotoxic RNK-16 lymphocyte
      granules indicating that the two new genes may be translated and stored as active
      granzymes.

PMID- 9144470
TI  - Costimulation of T cell proliferation by a chimeric B7-2 antibody fusion protein
      specifically targeted to cells expressing the erbB2 proto-oncogene.
AB  - T cells require at least two signals for activation and clonal expansion. The
      first signal conferring specificity is initiated by interaction of the T cell
      receptor with antigenic peptides in the context of MHC molecules. The second,
      costimulatory signal can be provided by cell surface molecules on APCs such as B7
      1 (CD80) and B7-2 (CD86), which interact with their counter-receptors on T cells.
      The absence of costimulatory signals presents one possible mechanism for tumor
      cells to escape immune surveillance. In experimental models transfection of B7
      genes into tumor cells can result in T cell-dependent tumor rejection. We have
      developed a novel approach to direct the costimulatory B7-2 molecule to the
      surface of target cells. Our approach is based on a chimeric fusion protein that
      consists of the extracellular domain of human B7-2 fused to a single-chain Ab
      domain (scFv) specific for the ErbB2 protein, a type I growth factor receptor
      overexpressed in a high percentage of human adenocarcinomas. This B7-2(225)
      scFv(FRP5) molecule expressed in the yeast Pichia pastoris and purified from
      culture supernatants is functionally active and binds to B7 counter-receptors and
      to ErbB2. B7-2(225)-scFv(FRP5) localizes specifically to the surface of ErbB2
      expressing target cells, thereby providing a costimulatory signal that results in
      enhanced proliferation of syngeneic T cells. Our results suggest that effective
      tumor vaccines for cancer immunotherapy could be created by targeting such
      chimeric ligands to the surface of tumor cells.

PMID- 9144471
TI  - Enhanced CTL responses mediated by plasmid DNA immunogens encoding costimulatory
      molecules and cytokines.
AB  - In the course of examining epitope-specific CTL responses to intramuscular
      plasmid DNA immunization with influenza nucleoprotein (NP)-expressing vectors, a
      nonimmunogenic mutant NP (NP(o)) was identified. The coding region of NP(o)
      differed from the wild-type A/PR/8/34 NP sequence (designated NP(v)) by three
      amino acid alterations in the carboxyl-terminal portion of the molecule remote
      from the H-2K(d) epitope (147-155) being monitored. Correction of these mutations
      restored the immunogenicity of the native sequence, indicating that sequence
      alterations remote from the CTL epitope in question can profoundly influence its
      immunogenicity. In an effort to identify general, nonstructural means of
      enhancing the CTL response to weak plasmid DNA immunogens, vectors were
      constructed expressing NP(o) in tandem with the costimulatory molecules B7-1 or
      B7-2. Co-linear expression of NP(o) with B7-2, but not B7-1, significantly
      increased the NP epitope-specific CTL response. In addition, coinjection of these
      NP(o) plasmids with granulocyte-macrophage CSF- and/or IL-12-expressing vectors
      also restored near native NP-specific CTL responses. Thus, the coexpression of
      certain costimulatory molecules and/or cytokines, in concert with a non-self gene
      delivered as an intramuscular plasmid DNA immunogen, can significantly enhance Ag
      specific CTL responses.

PMID- 9144472
TI  - Regulation of CD95 (Fas) ligand expression by TCR-mediated signaling events.
AB  - Stimulation of mature peripheral T cells by TCR engagement results in activation
      of signals that drive induction of cytokine gene expression and clonal expansion.
      However, under some conditions, engagement of the TCR leads instead to apoptosis.
      Recent studies demonstrate that TCR-stimulated apoptosis requires expression of
      CD95 ligand on activated T cells followed by an interaction between CD95 ligand
      and the CD95 receptor also expressed on this population. The experiments reported
      in this study were designed to address the signaling events triggered by TCR
      engagement that are important for regulating CD95 ligand gene expression. To
      approach this, we generated a luciferase reporter construct containing elements
      of the CD95 ligand promoter. Using a previously described mutant of the Jurkat T
      cell line, we show that proximal signaling events dependent on the presence of
      the CD45 tyrosine phosphatase are required for TCR-stimulated CD95 ligand
      expression. Transient transfection studies demonstrate further that TCR
      stimulated activation of the Ras signaling pathway is required for optimal
      activation of CD95 ligand. Next, in an effort to determine critical transcription
      factors that regulate CD95 ligand expression, we demonstrate a cyclosporin A
      sensitive nuclear factor-AT response element in the promoter region of this gene
      that is critical for optimal CD95 ligand reporter activity in stimulated T cells.
      Together, these studies begin a dissection of the biochemical events that lead to
      expression of CD95 ligand, a required step for TCR-induced apoptosis.

PMID- 9144473
TI  - Glutathione depletion is an early and calcium elevation is a late event of
      thymocyte apoptosis.
AB  - According to current understanding, several metabolic alterations form part of
      the common phase of the apoptosis process. Such alterations include a disruption
      of the mitochondrial transmembrane potential (delta psi(m)), a depletion of
      nonoxidized glutathione (GSH) levels, an increase in the production of reactive
      oxygen species (ROS), and an elevation in cytosolic free Ca2+ levels. Using a
      cytofluorometric approach, we have determined each of these parameters at the
      single cell level in thymocytes or T cell hybridoma cells undergoing apoptosis.
      Regardless of the apoptosis induction protocol (glucocorticoids, DNA damage, Fas
      cross-linking, or CD3epsilon cross-linking), cells manifest a near-to
      simultaneous delta psi(m) dissipation and GSH depletion early during the
      apoptotic process. None of the protocols for apoptosis inhibition (antioxidants,
      delta psi(m) stabilization, Bcl-2 hyperexpression, or inhibition of IL-1
      converting enzyme) allowed for the dissociation of delta psi(m) disruption and
      GSH depletion, indicating that both parameters are closely associated with each
      other. At a later stage of the apoptotic process, cells manifest a near
      simultaneous increase in ROS production and intracellular Ca2+ levels. Whereas
      the thapsigargin- or ionophore-induced elevation of calcium levels has no
      immediate consequence on delta psi(m') cellular redox potentials, or ROS
      production, pro-oxidants and menadione, an inducer of mitochondrial superoxide
      anion generation, cause a rapid (15 min) Ca2+ elevation. Together, these data
      suggest a two-step model of the common phase of apoptosis. After an initial delta
      psi(m) dissipation linked to GSH depletion (step 1), cells hyperproduce ROS with
      an associated disruption of Ca2+ homeostasis (step 2).

PMID- 9144474
TI  - Bidirectional regulation of human B cell responses by CD40-CD40 ligand
      interactions.
AB  - Positive and negative effects of CD40 ligation on human B cell function were
      suggested by the observation that mAb to CD40 ligand partially blocked the
      suppressive influences of anti-CD3-stimulated control CD4+ T cells, as well as
      the B cell stimulatory effects of anti-CD3 activated mitomycin C-treated CD4+ T
      cells. To examine the negative effects of CD40 ligation in greater detail, B
      cells were cultured with anti-CD3 activated mitomycin C-treated CD4+ T cells that
      expressed optimal levels of CD40 ligand; additional recombinant human CD40 ligand
      significantly suppressed Ig production, but not proliferation. In contrast, when
      B cells were stimulated with SAC (formalinized Cowan I strain Staphylococcus
      aureus) and IL-2 in the absence of T cells, small amounts of recombinant CD40
      ligand-stimulated Ig production, whereas larger quantities directly suppressed Ig
      secretion. The suppressive action of CD40 ligation on Ig production was most
      apparent after initial B cell activation. Moreover, IgD-memory B cells were
      significantly more sensitive to inhibition by CD40 ligation than IgD+ naive B
      cells. Engagement of CD40 not only suppressed Ig secretion by IgD- memory B
      cells, but also expression of CD38. Finally, activated B cells acquired the
      capacity to down-regulate CD40 ligand expression by stimulated CD4+ T cells more
      effectively than resting B cells. These results indicate that during T cell-B
      cell collaboration, engagement of CD40 can influence Ig production both
      positively and negatively, depending on the density of CD40 ligand as well as the
      stage of B cell activation and differentiation.

PMID- 9144475
TI  - Phenotypic and functional maturation of TCR gammadelta cells in the human thymus.
AB  - In contrast to thymic differentiation of TCR alphabeta cells, differentiation
      stages of TCR gammadelta cells are largely unknown. This report shows that CD1, a
      known marker of immature TCR alphabeta thymocytes, was expressed on some
      postnatal TCR gammadelta thymocytes. Only CD1+ TCR gammadelta thymocytes
      expressed recombination-activating gene-1 mRNA, and they were shown to
      differentiate into CD1- TCR gammadelta thymocytes. Functionally, sorted CD1- TCR
      gammadelta thymocytes proliferated in the presence of immobilized anti-CD3 Ab
      plus exogenous rIL-2 or rIL-15. Interestingly, in contrast to CD1- TCR alphabeta
      cells, CD1- TCR gammadelta thymocytes also proliferated extensively when cultured
      with exogenous rIL-2 or rIL-15 alone. FACS analysis as well as reverse
      transcription-PCR analysis showed that only CD1- TCR gammadelta thymocytes
      expressed IL-2Rbeta protein and mRNA. The differential expression of maturation
      markers, such as CD27, CD45RO, and CD45RA, as a function of expression of CD1 was
      similar in TCR gammadelta and TCR alphabeta thymocytes. An important exception is
      the expression of CD4 and CD8. Whereas TCR alphabeta thymocytes are mainly CD4
      CD8 double positive at the immature CD1+ stage and CD4 or CD8 single positive at
      the mature CD1- stage, CD1(bright) TCR gammadelta thymocytes all expressed CD4,
      but only some of them expressed CD8. Some CD1- TCR gammadelta thymocytes also
      expressed CD8, but were negative for CD4. Collectively, our data clearly show
      that CD1 is a useful marker to distinguish immature human TCR gammadelta
      thymocytes from functional mature gammadelta cells based on recombination
      activating gene-1 expression, in vitro differentiation, and phenotypic and
      functional characteristics.

PMID- 9144476
TI  - T cell deletion induced by chronic infection with mouse mammary tumor virus
      spares a CD25-positive, IL-10-producing T cell population with infectious
      capacity.
AB  - We found that T cells recognizing viral superantigen (vSAG) can be subdivided
      into two distinct functional subsets based on IL-2R alpha (CD25) expression.
      CD4+Vbeta6+CD25- and CD4+Vbeta6+CD25+ T cells were sensitive to vSAG activation.
      When obtained from BALB/c(SW) mice, both subsets were infected and capable to
      induce the tolerance process when transferred into noninfected recipients.
      However, in contrast to CD4+Vbeta6+CD25- cells, which were gradually deleted in
      MMTV(SW)-infected mice, the pool of CD4+Vbeta6+CD25+ lymphocytes was constant
      even at the end of the deletion process, and maintained a limited reactivity to
      vSAG-induced activation. The constant number of Vbeta6+CD25+ observed in infected
      mice could not be explained by their rapid turnover (deletion and renewal), as
      their proliferative rate measured by BrdU incorporation was similar in infected
      and naive mice, as well as in virus-nonspecific (Vbeta8.2+) cells. Neither was
      the Vbeta6+CD25+ subset dependent on vSAG activation since it was also present in
      MMTV-free mice and was not generated from Vbeta6+CD25- cells upon in vivo vSAG
      stimulation. Vbeta6+CD25+ T cells constitutively expressed IL-4 and IL-10 mRNA.
      IL-10 has been shown to be associated with viral, bacterial, and parasitic
      infections. This permanent CD25+ subpopulation may play a role in the control of
      viral infection and tolerance induction via vSAG recognition and IL-10
      production.

PMID- 9144477
TI  - Apoptosis within spontaneously accepted mouse liver allografts: evidence for
      deletion of cytotoxic T cells and implications for tolerance induction.
AB  - MHC-mismatched liver grafts are accepted spontaneously between many mouse
      strains. The underlying mechanism(s) is unclear. In the B10 (H2(b)) to C3H
      (H2(k)) strain combination used in this study, donor T cells within the liver
      were rapidly replaced within 2 to 4 days of transplantation with those of the
      recipient. Freshly isolated liver graft-infiltrating cells harvested on days 4
      and 7 exhibited strong CTL responses against donor alloantigens. CTL activity was
      reduced substantially, however, by day 14, although levels of CTL precursors in
      the spleen and liver remained high. Examination of the liver allografts by in
      situ terminal deoxynucleotidyltransferase-catalyzed dUTP-digoxigenin nick end
      labeling on days 4, 7, and 14 after transplantation revealed prominent apoptotic
      cells dispersed throughout the nonparenchymal cell population. When acute liver
      allograft rejection was induced by administration of IL-2 from days 0 to 4 post
      transplant (median survival time, 5 days), apoptotic activity (day 4) was reduced
      substantially, whereas CTL activity was enhanced. Nonparenchymal cells isolated
      from allografts of unmodified recipients 4, 7, and 14 days after transplantation
      exhibited significantly higher DNA fragmentation after 18-h culture than cells
      from liver isografts. Moreover, the level was 4 to 5 times higher than that of
      cells from IL-2-treated mice (on day 4). These observations suggest that T cell
      deletion, not regulation, may be responsible for spontaneous liver allograft
      acceptance. The molecular recognition events that cause apoptosis of infiltrating
      T cells and why this occurs within liver grafts, but not heart or skin grafts,
      remain to be elucidated.

PMID- 9144478
TI  - CD19 expression levels regulate B lymphocyte development: human CD19 restores
      normal function in mice lacking endogenous CD19.
AB  - Establishing signal transduction thresholds that regulate B lymphocyte responses
      to foreign Ags and tolerance to self Ags is critical for humoral immune
      responses. The effects of altered signaling thresholds in B lymphocytes were
      examined in CD19-deficient mice and transgenic mice that expressed human CD19 at
      varying densities. Human CD19 restored normal B cell function and development to
      CD19-deficient mice when expressed at levels comparable to those of circulating
      human B cells. While CD19 expression levels were found to be developmentally
      regulated and tightly controlled in normal mice, two- or threefold changes in
      cell surface CD19 expression in transgenic mice dramatically affected B cell
      development, mitogen responses, serum Ig levels, humoral immune responses, and
      germinal center formation. B cells from mice that overexpressed CD19 also had
      decreased levels of surface IgM and a cell surface phenotype consistent with
      increased signaling in these cells. These results suggest that CD19 may serve
      similar functions in humans and mice and that CD19 defines signaling thresholds
      in vivo for the Ag receptor as well as other cell surface receptors that regulate
      B lymphocyte selection, activation, and differentiation.

PMID- 9144479
TI  - CD40 is a functional activation antigen and B7-independent T cell costimulatory
      molecule on normal human lung fibroblasts.
AB  - CD40 is an important signaling and activation Ag found on certain bone marrow
      derived cells. Recently, CD40 also has been shown to be expressed by mesenchymal
      cells, including human fibroblasts. Little is known about the role of CD40 in
      fibroblasts. The current study investigates the hypothesis that CD40 expressed on
      lung fibroblasts is an activation structure and mechanism for interaction with
      hemopoietic cells. Communication between resident tissue fibroblasts and T cells
      is necessary for normal wound healing, and can be pathologic, resulting in tissue
      fibrosis. Signaling through CD40 with soluble CD40 ligand stimulated fibroblast
      activation, as evidenced by mobilization of nuclear factor-kappaB and by
      induction of the proinflammatory and chemoattractant cytokines IL-6 and IL-8. IFN
      gamma-primed lung fibroblasts costimulate T lymphocyte proliferation utilizing
      CD40, but not the well-studied costimulatory molecules B7-1 and B7-2. Data
      reported herein support the hypothesis that cognate interactions between tissue
      fibroblasts and infiltrating T lymphocytes, via the CD40/CD40L pathway, augment
      inflammation and may promote fibrogenesis by activating both cell types.

PMID- 9144480
TI  - CD16-expressing CD8alpha alpha+ T lymphocytes in the intestinal epithelium:
      possible precursors of Fc gammaR-CD8alpha alpha+ T cells.
AB  - T lymphocytes normally express their Ag receptors in association with the CD3
      proteins, which include CD3zeta. In CD3zeta eta(null) mice thymic and peripheral
      T lymphocytes do not express the TCR/CD3 complex on their surface due to
      retention in the endoplasmic reticulum of the remaining polypeptide chains.
      However, intestinal intraepithelial lymphocytes (iIEL) of CD3zeta eta(null) mice
      do express surface TCR, because the Fc epsilonRI gamma chain replaced the CD3zeta
      chain in the TCR/CD3 complex. Here we report that in a subset of CD8alpha alpha+
      iIEL the presence of the Fc epsilonRI gamma chain could be accounted for by the
      surface expression of the Fc gammaRIII(CD16) complex. Because in wild-type (wt)
      mice only CD16+ iIEL coexpressed Fc epsilonRI gamma and CD3zeta, we concluded
      that the presence of Fc epsilonRI gamma was dictated by its required
      participation of CD16 complex. CD8alpha alpha+ iIEL bearing CD16 and B220 were
      also detected in the intestinal mucosa of RAG-2(null) mice from 12 days after
      birth onward. Two independent experimental settings were used in an attempt to
      demonstrate that CD16+ iIEL matured into CD16- T cells. First, in the RAG-2(null)
      mice, iIEL responded to in vivo administration of an anti-CD3epsilon mAb by
      progression to a more mature stage of development, characterized by a loss of
      CD16 and B220. Secondly, a conversion to CD16- iIEL occurred upon transfer of wt
      CD16+ iIEL into RAG-2(null) mice. We conclude from these experiments that in both
      RAG-2(null) and wt mice, a precursor/progeny relationship may exists between
      CD16+ B220+ CD8alpha alpha+ and CD16- B220- CD8alpha alpha+ iIEL.

PMID- 9144482
TI  - Expression of an inducible type of nitric oxide (NO) synthase in the thymus and
      involvement of NO in deletion of TCR-stimulated double-positive thymocytes.
AB  - The present study investigates the role of nitric oxide (NO) in the deletion of
      TCR-stimulated double-positive (DP) thymocytes. Fetal thymi expressed mRNA for an
      inducible type of NO synthase (iNOS). The levels of iNOS mRNA became maximal
      around gestation day 18 with a decline after birth. Administration of anti-CD3
      mAb to fetal thymus organ culture (FTOC) or young mice resulted in enhanced
      expression of mRNAs for iNOS as well as IFN-gamma. Immunohistochemical analyses
      revealed that iNOS was produced in the corticomedullary junction and medulla. The
      effects of iNOS-induced NO on anti-CD3-unstimulated or anti-CD3-stimulated
      thymocytes were examined by culturing them in the presence or absence of a NO
      generating compound. Stimulation of DP thymocytes with anti-CD3 alone induced the
      generation of CD4(low)CD8(low) thymocytes. The subsequent exposure of these anti
      CD3-stimulated thymocytes to NO promoted down-regulation of CD4 and CD8
      expression. The recovery of viable DP cells was considerably reduced compared
      with stimulation with anti-CD3 or NO alone. Even in a viable DP population, high
      incidences of DNA strand breaks were detected in the CD4(low)CD8(low)
      compartment. In contrast to DP cells, the recovery of viable single-positive
      cells was not decreased but rather slightly enhanced by treatment with anti-CD3
      and/or NO. The recovery of anti-CD3-stimulated thymocytes were also reduced when
      cultured on the thymic stromal monolayer with the capacity to produce NO upon IFN
      gamma stimulation. These results indicate that NO, which is generated in
      association with TCR stimulation in the thymus, functions to induce deletion of
      DP thymocytes, especially when their TCR is stimulated.

PMID- 9144481
TI  - Wortmannin, a phosphatidylinositol 3-kinase inhibitor, blocks antigen-mediated,
      but not CD3 monoclonal antibody-induced, activation of murine CD4+ T cells.
AB  - Perturbation of several distinct T cell molecules, including the CD3/TCR complex,
      CD7, and CD28, activates phosphatidylinositol 3-kinase (PI3-K), but a clear
      consensus on the role of PI3-K in T cell activation has yet to emerge. We report
      here that CD3 mAb-induced IL-2 production by CD4+ T cells from DO11.10 TCR
      alphabeta-transgenic mice is refractory to the potent PI3-K inhibitor,
      wortmannin, demonstrating that activation under these conditions is independent
      of PI3-K. In marked contrast, wortmannin substantially inhibits IL-2 production
      elicited by Ag (OVA(323-339) peptide) presented by appropriate APCs (syngeneic
      B7+ B cell blasts) and blocks Ag-induced differentiation of naive CD4+ DO11.10 T
      cells into IL-4-producing cells. Wortmannin inhibits Ag-induced conjugate
      formation between T cells and B7+ B cell blasts. Because T cell activation by Ag
      requires stable interactions with APCs, this inhibitory effect on conjugate
      formation may underlie the ability of wortmannin to block Ag-induced IL-2
      production and differentiation.

PMID- 9144484
TI  - CD28 engagement and proinflammatory cytokines contribute to T cell expansion and
      long-term survival in vivo.
AB  - To mount a productive response to Ag, CD4+ T cells in mice must divide,
      differentiate, and survive at least until the Ag has been eliminated. It has been
      suggested that to accomplish this, T cells must receive two signals, one through
      their TCRs and a second through CD28. The second signal through CD28 has been
      thought to fulfill two roles, to stimulate T cell proliferation and to promote T
      cell survival. In this paper we confirm that CD28 engagement can contribute to
      vigorous T cell expansion in mice injected with superantigens. However, CD28
      engagement does not protect T cells produced during a superantigen-specific
      proliferative response from undergoing subsequent deletion. Even if CD28 is
      bound, 4 days after superantigen exposure, the majority of T cells produced in
      response to superantigen exposure are eliminated in vivo. In contrast, this loss
      of superantigen-stimulated T cells can be prevented by the inflammatory stimuli
      created by injection of bacterial LPS. This protection does not require
      engagement of CD28 by its ligands, B7-1 and B7-2. These data suggest that
      productive T cell responses in mice involve a number of signals, including those
      initiated through TCR and CD28, which are primarily involved in the activation
      and expansion of T cells, and others delivered by proinflammatory cytokines that
      protect an activated T cell from subsequent deletion.

PMID- 9144483
TI  - Impaired lymphokine secretion in anergic CD4+ T cells leads to defective help for
      B cell growth and differentiation.
AB  - The ability of anergic helper T cells to interact with resting B cells was
      examined in vitro. B cell growth and differentiation in cocultures were found to
      be dependent on the expression of CD40 ligand (CD40L) on the cloned T cells, and
      the expression of this molecule was only marginally blocked by the induction of
      anergy. In contrast, secretion of IL-3, IL-4, IL-5, and IL-6 within the
      cocultures was found to be significantly reduced following the induction of
      anergy, and this correlated with the development of a 3- to 10-fold decrease in
      the ability of the T cells to induce B cell proliferation and IgG secretion. In
      contrast to the B cells, the activation of the T cells in these cocultures did
      not result in proliferation; thus, the effects of T cell anergy observed on the B
      cell responses were independent of an ability of clonal anergy to block T cell
      clonal expansion. In one T cell clone (E6), lymphokine production was reduced in
      part because of an increased propensity to undergo apoptosis; nevertheless, two
      other clones (A.E7 and 16B.2) showed no reduced viability after anergy induction.
      Finally, the addition of rIL-2 to the anergic T cells significantly improved
      their helper activity relative to control cells; this was associated with a
      partial reversal of the IL-3, - 4, and -5 production defects. Therefore, clonal
      anergy can interfere with the delivery of helper lymphokines by T cells,
      resulting in a decreased capacity to stimulate the growth and differentiation of
      B cells.

PMID- 9144485
TI  - Development of effector CD8+ T cells in contact hypersensitivity occurs
      independently of CD4+ T cells.
AB  - Contact hypersensitivity (CHS) is a T cell-mediated response to hapten
      sensitization of the epidermis. Recent results from this laboratory indicated
      that hapten sensitization induces two populations of hapten-reactive T cells:
      CD8+ T cells producing IFN-gamma, which mediate the response, and CD4+ T cells
      producing IL-4 and IL-10, which function to limit the magnitude and the duration
      of the response. In the current report we first examined the hapten-presenting
      cell priming each of these T cell populations and then examined the influence of
      CD4+ T cell priming on the development of the CD8+ effector T cells. Isolation of
      hapten-presenting Langerhans cells from the lymph nodes of oxazolone-sensitized
      mice and transfer to naive mice resulted in the induction of both the regulatory
      CD4+ and the effector CD8+ T populations. Both CD4+ and CD8+ T cells expressing
      high levels of the activation determinants CD11a and CD44 appeared in the lymph
      nodes 3 days after hapten sensitization. The CD8+ T cells producing IFN-gamma and
      mediating CHS responses following transfer to naive mice were restricted to the
      high CD44-expressing population. In vitro activation of hapten-immune CD8+ T
      cells resulted in very low amounts (3 U/ml) of IL-2 production, whereas
      production of IL-2 by immune CD4+ T cells was approximately 70-fold higher (208
      U/ml). Despite this discrepancy in IL-2 production and the coincidental priming
      of CD4+ and CD8+ T cells by hapten-presenting Langerhans cells during hapten
      sensitization, the numbers of CD8+/high CD44-expressing T cells in the lymph
      nodes were nearly identical when CD4+ T cells were present or absent during
      hapten priming. These results indicate that coincidental priming of CD4+ (and
      CD8+) T cells by LC does not augment CD8+ T cell development in CHS.

PMID- 9144486
TI  - The Fas-deficient SCID mouse exhibits the development of T cells in the thymus.
AB  - The Fas Ag is a cell surface protein that mediates apoptosis and is highly
      expressed on thymocytes. However, the role of the Fas system in the thymus is
      unclear. To study the role of the Fas system in the thymus, we established a
      novel SCID mouse bearing the lpr (lymphoproliferation) mutation. Thymocytes from
      these mice differentiated into CD4+ CD8+ T cells and then underwent further
      differentiation into CD4+ CD8- or CD4- CD8+ single-positive T cells with a low
      surface expression of CD3, whereas B cell development remained unrescued. These
      TCR-positive T cells can proliferate in response to stimulation with PMA plus
      ionomycin, but not with third-party spleen cells. Furthermore, thymocytes from
      scid/lpr mice had a great variety of TCR Vbeta repertoires. These results suggest
      that the Fas system plays an essential role in regulating the development of
      intrathymic T cells as well as peripheral T cells.

PMID- 9144487
TI  - B7-blocking agents, alone or in combination with cyclosporin A, induce antigen
      specific anergy of human memory T cells.
AB  - T cell anergy refers to a functional state in which the cells are alive but
      unable to produce IL-2 after appropriate triggering. Lack of CD28 costimulation
      through CD80 and CD86 molecules on APC might play a causative role in anergy
      induction, as previously shown with T cell clones. We now developed a model of
      anergy induction in cultures of freshly isolated memory T cells. Addition of
      either CTLA-4Ig or blocking anti-CD80 and anti-CD86 mAbs, in combination with
      cyclosporin A, to cultures of PBMC with soluble Ag consistently resulted in Ag
      specific unresponsiveness, as evidenced upon antigenic rechallenge. In most
      experiments, the presence of cyclosporin A was not required, and blocking the B7
      CD28 interaction during antigenic stimulation was sufficient to induce
      unresponsiveness. Unresponsiveness was apparent at the level of T cell
      proliferation as well as at the level of IL-2 and IFN-gamma production, and T
      cell responses to unrelated Ags were intact. Induction of unresponsiveness
      correlated with lack of T cell proliferation in the induction culture and could
      largely be prevented by supplementing the induction cultures with rIL-2,
      indicating that lack of IL-2 was responsible for this altered functional state.
      Unresponsive T cells did not suppress the proliferation of autologous T cells in
      response to original or third-party Ags. On the other hand, culture with IL-2 and
      Ag could reverse established T cell unresponsiveness, pointing to anergy rather
      than deletion as the underlying mechanism. Anergy induction in freshly isolated
      memory T cells opens perspectives for treatment of autoimmune and allergic
      diseases.

PMID- 9144488
TI  - CIITA-dependent and -independent class II MHC expression revealed by a dominant
      negative mutant.
AB  - The MHC class II transactivator gene (CIITA) coordinately controls the expression
      of the three major human class II genes, HLA-DR, HLA-DQ, and HLA-DP. Indeed,
      patients with one form of MHC class II immunodeficiency disease, due to defective
      CIITA genes, lack expression of all three isotypes. Nevertheless, there is
      substantial evidence that human class II genes are not always coordinately
      regulated, raising the possibility that CIITA-independent, isotype-specific class
      II regulatory pathways exist. To address this issue, we have generated a dominant
      negative mutant of CIITA that lacks the acidic transcription-activating N
      terminus, but retains the proline/serine/threonine-rich domain. Three newly
      produced anti-CIITA mAbs revealed that this mutant protein lacked N-terminal
      epitopes. In this study, we report that this CIITA dominant negative mutant
      repressed the constitutive expression of all three class II isotypes in human EBV
      B cell lines, as well as IFN-gamma-induced class II transcription in HeLa cells.
      However, in a CIITA-deficient, EBV-transformed B cell line, clone 13, the
      dominant negative mutant did not alter the endogenous expression of the HLA-DQ
      gene. Taken together, these data demonstrate the existence of both CIITA
      dependent and -independent class II regulatory pathways. Furthermore, our data
      provide evidence that the latter pathways can be isotype specific.

PMID- 9144489
TI  - Genomic organization, promoter region analysis, and chromosome localization of
      the mouse bcl-x gene.
AB  - The bcl-x gene, a bcl-2 family member, is highly regulated during lymphoid
      development, and its expression modulates apoptosis in lymphoid and other cell
      populations. Several forms of bcl-x mRNAs with different biologic functions have
      been described in rodents and humans. In this study, we have determined the
      organization and promoter region of the mouse bcl-x gene in an effort to
      understand the molecular basis for the different bcl-x mRNA species identified in
      tissues. We show that mouse bcl-x maps to the distal mouse chromosome 2 at
      approximately 89 cM, and exhibits a three-exon structure with an untranslated
      first exon and a facultative first intron. The coding region of bcl-xL is
      generated by the juncture of exons II and III through a splicing reaction,
      whereas bcl-xS is generated by an alternatively utilized donor splice site
      located within exon II. Analysis of multiple cDNAs and primer extension
      experiments revealed major transcription initiation sites in brain and thymus
      within a GC-rich region, with multiple Sp1-binding motifs located upstream of
      exon I. Another promoter was mapped to a 57-bp region localized upstream of the
      translation initiation codon by transfection of reporter constructs into FL5.12
      and K562 cell lines. The remarkable similarity between the genomic regions of bcl
      2 and bcl-x suggests that these genes have evolved from a common ancestral gene
      or through gene duplication.

PMID- 9144490
TI  - Expression of the murine CD21 gene is regulated by promoter and intronic
      sequences.
AB  - Murine CD21 gene products are expressed primarily on the surface of B lymphocytes
      and follicular dendritic cells. To identify the genetic elements that control the
      tissue-specific expression of the CD21 gene, we analyzed, via transient
      transfections, the 5' proximal promoter region of the CD21 gene (1272 bp 5' of
      the initiating ATG). This region possessed strong promoter activity, but it was
      not tissue specific, in that T cell expression was equivalent to that of B cells.
      These data suggested that the anticipated tissue-specific control element(s) lies
      3' of the initiating ATG. Analysis of a novel minigene construct that possessed
      both the 5' promoter region and a large region (9 kb) of the CD21 gene 3' of the
      initiating ATG demonstrated the expected tissue-specific expression. Further
      analysis using the luciferase reporter system indicated that such control
      elements reside in the first intron (5.5 kb in size), which separates the exons
      encoding the signal sequence and the first extracellular short consensus repeat
      domain of the mature protein. Further dissection of intron 1 demonstrated that
      the sequences controlling the tissue-specific expression of the murine CD21 gene
      are contained in the 5' 1.6-kb region of this intron. This 1.6-kb fragment was
      fractionated into an 800-bp sequence at the 5' end that showed very significant
      inhibitory activity in both B and T cells and a 3' 800-bp sequence that
      demonstrated moderate repression in T cells, but enhancer activity in B cells.
      These data suggest this region of the CD21 gene possesses a number of
      functionally distinct sites that positively and negatively regulate CD21 gene
      transcription.

PMID- 9144491
TI  - CD40 cross-linking induces Ig epsilon germline transcripts in B cells via
      activation of NF-kappaB: synergy with IL-4 induction.
AB  - Transcription of unrearranged (germline) Ig heavy chain C region (C(H)) genes is
      required before Ab class switch recombination. Although the cytokine IL-4 is well
      known to induce transcription of unrearranged C epsilon and C gamma1 genes, it
      has been shown recently that CD40 signaling also induces these transcripts in
      mouse B cells. We report in this study that treatment of mouse M12.4.1 B lymphoma
      cells with soluble CD40 ligand (CD40L)-CD8alpha fusion protein modestly induces
      the promoter for germline epsilon transcripts, and that this induction synergizes
      with IL-4. CD40L induces binding of nuclear factor (NF)-kappaB/Rel proteins to
      two tandem kappaB sites located immediately 3' to the IL-4-responsive region of
      the mouse germline epsilon promoter. The epsilon-124/-56 promoter segment
      containing the IL-4 response region and the two kappaB sites is sufficient to
      transfer CD40L and IL-4 inducibility to a minimal c-fos promoter when transiently
      transfected into M12.4.1 cells. Mutation of the two kappaB sites eliminates
      induction by CD40L or by IL-4, and treatment of M12.4.1 cells with inhibitors of
      NF-kappaB activation prevents induction of endogenous germline epsilon
      transcripts in M12.4.1 cells. In addition to the NF-kappaB/Rel complexes induced
      by CD40L, two nuclear complexes, each which contain both STAT6 and NF-kappaB/Rel
      proteins, are induced in splenic B cells by a combination of CD40L and IL-4, and
      bind to the CD40L/IL-4-responsive region of the germline epsilon promoter. The
      presence of these complexes may explain the synergistic induction of
      transcription by CD40L and IL-4 mediated through this promoter segment.

PMID- 9144492
TI  - Dyad symmetry within the mouse 3' IgH regulatory region includes two virtually
      identical enhancers (C alpha3'E and hs3).
AB  - The transcription of the murine Ig heavy chain locus is regulated not only by the
      intronic enhancer, E mu, but also by a 3' regulatory region located downstream of
      the C alpha membrane exon. Several DNase I-hypersensitive sites (hs1-4) and
      enhancer elements (e.g., C alpha3'E) have been identified in this 3' regulatory
      region, and some of these were suggested to comprise a locus control region.
      However, little is known about the coordinate regulation or function of these
      individual elements. Here we provide evidence that C alpha3'E and hs3 are
      virtually mirror images of each other and demarcate the edges of an approximately
      25-kb region of quasi-dyad symmetry with 3'alphaE(hs1,2) at its center. Flanking
      3'alphaE(hs1,2) are inverted repeats and families of repetitive sequences
      uniquely located in this region. We have observed that, like 3'alphaE(hs1,2) and
      hs3, C alpha3'E is DNase I hypersensitive in plasma cell lines, but not in a pre
      B cell line. Additionally, we found that C alpha3'E and hs3 show significant
      transcriptional synergy in transfection assays only in a plasma cell line. The
      DNA topology of the 3' regulatory region coupled with new and existing data on
      the activity of its individual enhancers during B cell differentiation lead us to
      propose a biphasic model for the activity of this region. According to our model,
      one unit, consisting of the 3'-most enhancer, hs4, is active early and throughout
      B cell development. The second unit, which comprises C alpha3'E, 3'alphaE(hs1,2),
      and hs3, becomes active later in development, when it contributes to such
      processes as class switching and increased levels of Ig heavy chain gene
      transcription in plasma cells.

PMID- 9144493
TI  - The pentanucleotide ATTGG, the "inverted CCAAT," is an essential element for HLA
      class I gene transcription.
AB  - The HLA class I genes, HLA-A, -B, and -C, contain an inverted CCAAT sequence
      (ATTGG) located 20 bp upstream of the canonical CCAAT and approximately 70 bp
      upstream of the transcription initiation site. We have investigated the
      transcriptional function of the class I inverted CCAAT sequence using the HLA
      normal cell line, HeLa. Deletion, mutation, or inversion of the inverted CCAAT
      sequence abrogated or reduced the activity of the class I promoter, as assessed
      by luciferase reporter gene assays in transient gene expression experiments. This
      activity coincided with occupancy of the inverted CCAAT motif, as tested by
      electrophoretic mobility shift assays using the wild-type sequence and mutated
      variants of the sequence. The ATTGG-binding protein was not CP2, NF-1, or other
      known CCAAT-binding proteins, but the complex may contain a CP1/NF-Y-like
      protein. Our results indicate that this inverted CCAAT sequence is an essential
      element for the expression of HLA class I genes and that its transcriptional
      activity depends upon the sequence, position, and orientation of the
      pentanucleotide.

PMID- 9144495
TI  - IgH gene rearrangements on the unexpressed allele in rabbit B cells.
AB  - VDJ genes are assembled in two sequential DNA recombination steps, rearrangement
      of D and J(H) gene segments followed by rearrangement of a V(H) gene segment. In
      mouse and human, VDJ gene rearrangements occur in a regulated step in which D
      rearranges to J(H) on both alleles before V(H) rearranges to DJ. To determine how
      VDJ gene rearrangements are regulated in the rabbit, we studied the IgH gene
      rearrangements in rabbit B cells by examining the gene rearrangement on the
      unexpressed allele in rabbit hybridomas. By Southern blot analysis with probes
      from the J(H) and 3'V(H)1 regions, we found that approximately 50% of the
      hybridomas had DJ gene rearrangements on the unexpressed allele, whereas the
      remaining 50% did not rearrange either J(H) or V(H) genes. Unexpectedly, we found
      a VD gene rearrangement on the unexpressed allele of a rabbit B cell line, so we
      PCR-amplified the VD gene rearrangements from splenocyte DNA and found a few VD
      gene rearrangements in normal B cells as well. The data taken together show that
      IgH gene rearrangements in rabbit B cells are regulated differently than those in
      the mouse, and we hypothesize that in some B cells, VDJ gene rearrangements
      proceed through a VD intermediate rather than through a DJ intermediate.

PMID- 9144494
TI  - Functional and pharmacokinetic properties of antibody-avidin fusion proteins.
AB  - In an attempt to produce broadly useful targeting agents, genetic engineering and
      expression techniques have been used to produce Ab-avidin fusion proteins.
      Chicken avidin has been fused to mouse-human chimeric IgG3 at the end of C(H)1
      (C(H)1-Av), immediately after the hinge (H-Av), and at the end of C(H)3 (C(H)3
      Av). Fusion heavy chains of the expected molecular mass were expressed, assembled
      with a co-expressed light chain, and secreted. The resulting molecules continued
      to bind Ag. They also bound biotinylated human serum albumin; C(H)3-Av had
      reduced affinity (K(A) = 5.13 x 10(9) M(-1)) compared with the tetrameric avidin
      (K(A) = 1 x 10(15) M(-1)), but greater affinity than monomeric avidin (K(A) = 1 x
      10(7) M(-1)). Importantly, the avidin-IgG fusion proteins had a longer serum t1/2
      in rats than avidin. The favorable pharmacokinetic parameters suggest that these
      avidin fusion proteins can be used effectively to deliver biotinylated ligands
      such as drugs and peptides to locales expressing any Ag recognized by the
      associated Ab.

PMID- 9144496
TI  - HLA-DMA and HLA-DMB gene expression functions through the conserved S-X-Y region.
AB  - The MHC class II homologous proteins HLA-DMA and HLA-DMB function in the loading
      of peptides onto class II molecules. Like the class II genes, the HLA-DM genes
      contain upstream regulatory sequences similar to the S-X-Y regulatory region as
      well as additional putative regulatory sites. To determine whether the DM genes
      are regulated in a similar manner as class II genes, a series of in vivo and in
      vitro analyses was performed. Deletion analysis showed that expression from the
      DM promoters is dependent on the conserved S-X-Y region. The class II-specific
      transcription factors RFX and CIITA are also required for expression, as cell
      lines deficient in these factors failed to allow transcription from the DM
      promoters. In addition, in vivo footprint analysis showed the putative X and Y
      boxes to be occupied by transcription factors in wild-type B cells, but not in
      RFX-deficient B cells. In astrocytes, IFN-gamma treatment induced increased
      occupancy of these sites. None of the other putative regulatory sites was
      occupied in vivo, indicating that they may not be functional. Finally, gel shift
      analysis showed synergistic complex formation between proteins that bind to the
      putative X boxes of the DM genes, as is found for the DRA gene. Therefore, the DM
      genes share a common mechanism of regulation with the class II genes.

PMID- 9144497
TI  - Defects in cell-mediated immunity affect chronic, but not innate, resistance of
      mice to Mycobacterium avium infection.
AB  - To investigate the role of cell-mediated immunity in the control of Mycobacterium
      avium infection, we studied the effects of targeted gene disruptions in
      components of the T lymphocyte-dependent, macrophage-mediated response on
      resistance of mice to this pathogen. Normal mice developed a chronic,
      asymptomatic infection, with rapid induction of mRNAs for IFN-gamma, IL-12, and
      TNF-alpha in spleen, liver, and lung. Bacterial loads in gene knockout, scid, and
      wild-type mice were indistinguishable for the first 4 wk of infection. However,
      by 8 wk postinfection, scid mice as well as animals with a targeted disruption of
      the IFN-gamma gene showed enhanced bacterial growth compared with wild-type
      controls. In contrast, knockout mice lacking the genes for the TNF-alpha p55/p75
      receptors or inducible nitric oxide synthase not only developed comparable
      bacterial loads to wild-type animals, they also failed to display the
      splenomegaly and profound suppression of mitogen-induced lymphocyte proliferative
      responses evident in infected wild-type controls. Thus, M. avium is clearly
      distinct from other intracellular pathogens (e.g., Leishmania monocytogenes,
      Toxoplasma gondii, and Mycobacterium tuberculosis) whose initial replication in
      the host is tightly controlled by Th1-dependent effector mechanisms. Instead, the
      major effect of host cell-mediated immunity is to limit bacterial growth during
      the chronic phase of infection. Surprisingly, inducible nitric oxide appears to
      be more important for the immunopathology than for the host resistance induced by
      this bacterial pathogen.

PMID- 9144498
TI  - In infection with Schistosoma mansoni, B cells are required for T helper type 2
      cell responses but not for granuloma formation.
AB  - The immune response and immunopathologic manifestations in schistosomiasis are
      largely dependent on Ag-specific CD4+ Th cells. In turn, the
      stimulatory/regulatory function of the Th cells is dependent on signals emanating
      from accessory cells. B cells are capable of functioning as accessory cells, and
      their role in experimental murine schistosomiasis was investigated by using mice
      with targeted mutations in the J(H) locus. This phenotype results in the absence
      of B cells and of Ab production. After 7.5- to 8-wk infections, mesenteric lymph
      node cells from the JHD B-less mice displayed lower proliferative responses to
      schistosomal egg Ag than did cells from infected control mice. Most importantly,
      compared with cells from controls, egg Ag-stimulated JHD lymph node cells
      produced significantly higher amounts of the Th1 response-associated cytokines
      IFN-gamma and IL-12, while their production of the Th2-type cytokines IL-4 and IL
      10 was dramatically reduced or undetectable. Similarly, irradiated splenocytes
      from uninfected JHD mice, used as APC, elicited significantly stronger Th1 and
      weaker Th2 responses from egg Ag-specific CD4+ Th cells than splenocytes from
      control mice. Despite these sharply contrasting cytokine profiles, there were no
      significant differences either in the size and composition of the resulting egg
      granulomas or in the number of deposited eggs in the livers of infected JHD vs
      control mice. Taken together, the findings in the JHD mouse reflect an impairment
      in the ability to mount a Th2 response, which translates into a loss of the Th1
      to Th2 switch characteristically seen in normal schistosome-infected mice. These
      results suggest that B cells promote Th2-type responses, and that typical
      granulomatous responses proceed in their absence.

PMID- 9144500
TI  - Immunosuppressive activity of cloned natural killer (NK1.1+) T cells established
      from murine tumor-infiltrating lymphocytes.
AB  - To elucidate the role of NK1.1+ T cells in the antitumor immune response, we
      established cloned NK1.1+ T cell lines from tumor-infiltrating lymphocytes (TIL)
      of B16 melanoma, and examined their mode of action in generating antitumor
      effector T cells both in vitro and in vivo. An NK1.1+ T cell clone (TM4.2) was
      phenotypically CD3+ TCR-alphabeta+ CD4- CD8- NK1.1+, and CD28+. The TM4.2 cells
      suppressed the in vitro generation of anti-B16 melanoma CTLs, but not the
      effector function of CTLs. The results using a transwell membrane suggested that
      their suppressive activity was mediated by both soluble factors and a direct cell
      to cell interaction. As for the soluble factors, the suppressive activity of the
      culture supernatant of TM4.2 cells was neutralized by anti-TGF-beta mAb, and the
      TM4.2 cells actually produced a considerable amount of TGF-beta. On the other
      hand, the TM4.2 cells showed a high level of cytolytic activity against B cell
      blasts and CD80-transfected P815, and such cytolytic activity was reduced by the
      addition of anti-CD80 mAb. In addition, NK1.1+ T cells in the freshly isolated
      TIL were revealed to express CD28. Furthermore, the TM4.2 cells suppressed the in
      vitro generation of anti-allo CTLs irrespective of the MHC haplotype. Finally,
      the TM4.2 cells suppressed the in vivo antitumor immune response. Collectively,
      these findings demonstrate that NK1.1+ T cells in TIL show immunosuppressive
      activity in the antitumor immune response through the production of TGF-beta and
      the preferential cytolysis of B7-expressing cells.

PMID- 9144499
TI  - Borrelia burgdorferi outer surface protein A (OspA) activates and primes human
      neutrophils.
AB  - Lyme disease is caused by infection with the spirochete Borrelia burgdorferi and
      is characterized by bacterial persistence and inflammation of many host tissues.
      B. burgdorferi express outer surface lipoproteins, including OspA, with
      inflammatory properties that could contribute to the localized tissue
      inflammation. Neutrophils are the predominant infiltrate into the inflamed
      arthritic joints, and are crucial for controlling the spirochete infection. They
      may also contribute to the joint pathology associated with Lyme arthritis. This
      study examines the effect of OspA on the activities of the neutrophil. Picomolar
      concentrations of OspA induce surface markers associated with neutrophil
      activation: increased CD10 and CD11b expression; decreased CD62-L expression; and
      an increased adherence to extracellular matrix. These events were similar in
      kinetics and magnitude to those induced by the strong activators LPS and FMLP.
      Like LPS, OspA could prime neutrophils for FMLP-induced release of lysosomal
      granules and production of superoxide. Thus, models of Lyme arthritis should
      include the possible contribution of direct activation of neutrophils to both
      defense and disease.

PMID- 9144501
TI  - Antibody to Mac-1 or monocyte chemoattractant protein-1 inhibits monocyte
      recruitment and promotes tumor growth.
AB  - Human tumors are frequently infiltrated by numerous monocytes/macrophages, which
      can be found within the tumor mass (intratumoral) or surrounding the tumor
      (peritumoral). The functional role that these monocytes/macrophages play in tumor
      growth is controversial. To address this issue we inhibited intratumoral
      monocyte/macrophage recruitment with mAbs that either blocked integrin function
      or neutralized a tumor-produced chemotactic protein. Both treatments
      significantly increased tumor formation and accelerated tumor growth.
      Surprisingly, the same results were obtained when recruitment of peritumoral or
      intratumoral monocytes/macrophages was blocked. Our findings are contrary to one
      of the purported roles of monocytes/macrophages, particularly in the peritumoral
      area, since we found no evidence for monocyte/macrophage-supported tumor growth.
      These results provide direct evidence that intratumoral as well as peritumoral
      monocytes/macrophages act to limit tumor size in the early stages following tumor
      inoculation and provide a mechanism that accounts for monocyte/macrophage
      recruitment to human tumors.

PMID- 9144502
TI  - Phosphorylation and subcellular redistribution of pleckstrin in human
      neutrophils.
AB  - Pleckstrin, originally described as a major substrate of protein kinase C (PKC)
      in platelets, was found to be highly expressed in human neutrophils
      (intracellular concentration, approximately 15 microM). As PKC isoforms play an
      important role in mediating neutrophil antimicrobial responses, we studied the
      regulation of pleckstrin phosphorylation in response to inflammatory stimuli.
      Following treatment of neutrophils with FMLP, 12-O-tetradecanoylphorbol-13
      acetate, or opsonized zymosan, pleckstrin was rapidly phosphorylated, which
      resulted in a shift in its electrophoretic mobility. Several lines of evidence
      suggest that pleckstrin is phosphorylated in part by a nonconventional PKC
      following stimulation by FMLP: 1) chelation of intracellular Ca2+ had only a
      partial inhibitory effect; 2) diacylglycerol kinase inhibitors shortened the
      duration of phosphorylation, while the phosphatidic acid phosphohydrolase
      antagonist propranolol extended it; and 3) wortmannin and erbstatin blocked the
      phosphorylation of pleckstrin. These results suggest that nonconventional PKC
      isoforms, possibly delta or zeta, mediate the phosphorylation of pleckstrin. Both
      PKCdelta and -zeta are expressed in human neutrophils. Increased association of
      pleckstrin with both microsomes and with the cytoskeleton was observed in
      stimulated cells. These findings suggest that phosphorylation by nonconventional
      PKC isoforms induces a conformational change in pleckstrin that promotes its
      interaction with membranes and/or with the cytoskeleton. Such a translocation may
      serve to target proteins or lipids recognized by pleckstrin homology domains to
      sites where they can contribute to the microbicidal response.

PMID- 9144503
TI  - Neutrophil platelet endothelial cell adhesion molecule-1 participates in
      neutrophil recruitment at inflammatory sites and is down-regulated after
      leukocyte extravasation.
AB  - Platelet endothelial cell adhesion molecule-1 (PECAM-1), a member of the Ig
      superfamily, is found on endothelial cells and neutrophils, and has been shown to
      be involved in the migration of leukocytes across the endothelium. Although
      studies have supported a role for endothelial PECAM-1 in this process, the
      participation of neutrophil PECAM-1 in vivo has not been unambiguously
      demonstrated. Therefore, to examine the involvement of neutrophil PECAM-1 in
      leukocyte recruitment, we studied the effect of a blocking Ab against murine
      PECAM-1 on neutrophil recruitment in an established model of murine peritonitis
      and in a murine model for studying leukocyte-endothelial interactions involving
      the human vasculature. These studies not only confirmed that neutrophil PECAM-1
      is important in the accumulation of neutrophils at inflammatory sites, but that
      extravasated neutrophils displayed decreased surface expression of PECAM-1. In
      vitro, the surface expression of murine neutrophil PECAM-1 was not decreased
      significantly by inflammatory mediators, but was reduced after transendothelial
      migration. These studies, consistent with previous in vitro observations, confirm
      that neutrophil PECAM-1, as well as endothelial PECAM-1, is involved in the
      recruitment of neutrophils into inflammatory sites in vivo, and suggest that the
      expression of neutrophil PECAM-1 is down-regulated after extravasation into
      inflamed tissues possibly as a result of engagement of its ligand.

PMID- 9144504
TI  - Novel anti-inflammatory compounds induce shedding of L-selectin and block primary
      capture of neutrophils under flow conditions.
AB  - Leumedins are small molecules that inhibit neutrophil movement into inflamed
      tissues. These compounds have been shown to inhibit the adherence of neutrophils
      in static adhesion assays mediated by beta2-integrins. We now report that
      leumedins, like activating agents, induce the loss of L-selectin from the
      neutrophil surface. The loss of L-selectin is unrelated to the inhibition of
      static adhesion, since neutrophils that have been pretreated with leumedins to
      cause shedding of L-selectin, followed by removal of drug, adhere normally in a
      static adhesion assay, and this adhesion is inhibited upon readdition of
      leumedin. In an assay of adhesion to endothelial cells under conditions of
      physiologic wall shear stress, leumedins prevent both primary capture of
      neutrophils mediated by L-selectin and firm adherence mediated by beta2
      integrins.

PMID- 9144505
TI  - Early embryo loss is associated with the prior expression of macrophage
      activation markers in the decidua.
AB  - In early embryo loss, the activation of maternal immune effector mechanisms play
      a critical role in determining the success or failure of a pregnancy. We have
      previously shown that increased nitric oxide production by decidual macrophages
      is involved in early embryo loss occurring at day 12 of gestation. In this study,
      using reverse transcription-PCR and Southern blotting, the expression of
      inducible nitric oxide synthases (iNOS) and TNF-alpha mRNA was determined to
      quantify macrophage activation in individual murine embryos in a model of
      spontaneous early embryo loss. At day 8 of gestation, 32 and 29% of embryos with
      no apparent pathology showed an increase in iNOS and TNF-alpha mRNA expression,
      respectively. This corresponds to the natural resorption rate seen in the mouse
      model. In addition, the percentage of embryos with increased iNOS and TNF-alpha
      mRNA expression was further augmented when pregnant mice were induced to abort at
      a higher rate. These results showed, for the first time, a correlation between
      increased iNOS and TNF-alpha expression and embryo resorption. The results
      provide evidence for the presence of activated macrophages at implantation sites
      before overt embryo damage occurs.

PMID- 9144506
TI  - Active oxidants mediate IFN-alpha-induced microvascular alterations in rat
      mesentery.
AB  - The present study was designed to investigate the influences of IFN-alpha on the
      microcirculatory hemodynamics. The mesenteric microcirculation of male Wistar
      rats was observed through an intravital fluorescence microscopic system. The
      leukocyte behavior, RBC velocity, and albumin leakage were monitored
      simultaneously before and after a continuous infusion of IFN-alpha. In other
      rats, the oxidant-sensitive fluorescence probe dihydrorhodamine-123 (DHR)
      fluorescence was observed in the same set up. Administration of IFN-alpha
      increased the number of adherent and emigrated leukocytes and decreased the RBC
      velocity in mesenteric venules. Oxidative stress indicated by DHR fluorescence
      was exacerbated in microvessels of IFN-alpha-treated rats. Following the
      leukocyte recruitment and oxidative stress, an exaggerated albumin leakage was
      observed. Thrombus formation in venules and hemorrhage along venules were
      frequently observed in rats treated with IFN-alpha. N,N'-dimethylthiourea, a
      scavenger of hydrogen peroxide and a hydroxyl radical, largely prevented these
      microvascular responses. Pretreatment of rats with mAb directed against either
      CD18 or ICAM-1 also attenuated the IFN-alpha-induced microvascular alterations.
      It is concluded, therefore, that a high concentration of IFN-alpha stimulates
      CD18/ICAM-1-dependent adhesive interactions with endothelial cells and oxidant
      production of leukocytes, which leads to microcirculatory derangements
      characterized by decreased barrier function and reduced anticoagulant activity of
      venular endothelial cells.

PMID- 9144507
TI  - Chloroquine inhibits processing of tumor necrosis factor in lipopolysaccharide
      stimulated RAW 264.7 macrophages.
AB  - TNF, a potent immunoregulatory cytokine, is associated with inflammatory diseases
      such as rheumatoid arthritis, multiple sclerosis, and cerebral malaria when
      produced in excess. Antimalarial agents such as chloroquine and
      hydroxychloroquine have been used to treat some rheumatic diseases. Chloroquine
      was reported to inhibit production of TNF, although the underlying mechanism is
      poorly understood. In RAW 264.7 cells stimulated with LPS, addition of
      chloroquine at nontoxic concentrations did not inhibit induction of TNF mRNA and
      NF-kappaB activity. In the same cells, synthesis and steady state level of 26-kDa
      pro-TNF were also not significantly reduced by addition of chloroquine, while
      only small amount of 17-kDa mature TNF was detected in the medium. A pulse-chase
      experiment of pro-TNF produced in chloroquine-treated cells showed significant
      inhibition of processing of prohormone. Hydroxychloroquine showed similar
      inhibitory effect, whereas other lysosomal inhibitors such as ammonium chloride
      and methylamine had no effect on the production of TNF. Our results suggest that
      chloroquine inhibits production of TNF at the step of processing of membrane
      bound pro-TNF to make soluble mature protein in a lysosome-independent manner.

PMID- 9144508
TI  - Neutrophils as a source of putative restriction proteases: degradation of
      mammalian and yeast proteins monitored by two-dimensional gel electrophoresis.
AB  - We have compared the ability of intact neutrophils to degrade a complex substrate
      of proteins from mammalian and yeast origin. The substrate was obtained by
      biosynthetic labeling, and subsequent lysis of K562 cells (leukemic cell line)
      and of yeast culture. The mammalian substrate consisted of 619 and the yeast
      substrate of 185 different polypeptides, as visualized and represented on two
      dimensional gel patterns. Upon incubation of the mammalian substrate with
      neutrophils, the bulk of spots disappeared so rapidly that after 240 min of
      incubation only 21 spots were detectable. Just one spot remained unaltered in its
      intensity throughout the whole period of incubation. About 440 spots reveal a
      t1/2 shorter than 8 min. Yeast substrate is represented by a smaller number of
      the starting polypeptides (185) from which 55 spots "survive" the neutrophil
      treatment. About 30 spots have a t1/2 shorter than 8 min. We conclude that
      neutrophils are equipped with a potent proteolytic apparatus, and this is capable
      of eliminating various proteins in a highly efficient manner. The system is much
      less effective in eliminating proteins from distant species, like yeast. Although
      the cells governing and regulating the immune system are clearly of lymphoid
      origin, it might well be that the preimmune task of eliminating self antigens in
      a manner as predicted in the restriction protease hypothesis is performed by
      neutrophils.

PMID- 9144509
TI  - Leukotriene C4 secretion from normal murine mast cells by a probenecid-sensitive
      and multidrug resistance-associated protein-independent mechanism.
AB  - P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) are
      members of the superfamily of ATP-binding cassette transporter proteins. Because
      the ATP-dependent export system has been implicated in the release of leukotriene
      C4 (LTC4), we examined the roles of P-gp and MRP in the release of LTC4 from
      normal murine mast cells (MC-9). We have previously shown that MC-9 cells express
      P-gp at the level of protein and mRNA. In the present study, MRP expression in MC
      9 cells was examined at the protein level by anti-MRP Ab, using flow cytometry
      and at the level of mRNA by PCR and Northern blot analyses. MC-9 cells were
      stimulated with calcium ionophore A23187 for 15 min in the presence or the
      absence of various concentrations of cyclosporin A (CsA) and its
      nonimmunosuppressive analogue CsA-1, which are known to inhibit P-gp efflux
      function, or in the presence or the absence of probenecid, an organic ion
      transport inhibitor that appears to inhibit MRP-mediated transport function.
      Culture supernatants were collected, and LTC4 was measured by ELISA assay. CsA
      and CsA-1 had no effect on LTC4 secretion from MC-9 cells, suggesting that P-gp
      is not involved in LTC4 release from MC-9 cells. In contrast, probenecid, in a
      concentration-dependent manner, inhibited LTC4 secretion from MC-9 cells without
      inhibiting its synthesis. However, MC-9 lacked MRP at both the protein and mRNA
      levels. These data suggest that LTC4 is secreted by normal mast cells by a
      probenecid-sensitive mechanism that is independent of MRP.

PMID- 9144510
TI  - Inflammatory cytokines IFN-gamma plus TNF-alpha induce regulated expression of
      CD80 (B7-1) but not CD86 (B7-2) on murine fibroblasts.
AB  - Optimal T cell activation requires signals delivered via both the TCR and the
      costimulatory receptors. Considerable experimental data now suggest that this
      costimulatory signal is generated predominantly by CD28 when engaged by its
      ligands CD80 (B7-1) and/or CD86 (B7-2). Whether T cell activation is controlled
      in part by regulated CD80 and/or CD86 expression has been incompletely explored.
      Here, we report that CD80 can be expressed constitutively by murine fibroblasts
      and up-regulated after treatment with IFN-gamma plus TNF-alpha. CD80 expression
      and function was confirmed by 1) Northern analysis, 2) specific
      immunoprecipitation of a approximately 69-kDa surface protein that comigrated
      with CD80 precipitated from CD80-transfected CHO cells, and 3) two independent
      assays for costimulation of Ag-specific T cell activation. Taken together, these
      observations suggest that CD28/CTLA-4 ligands are expressed on a wider variety of
      tissues than previously suspected and that their expression is dynamically
      regulated. Consequently, these results might explain previous observations that
      inflammatory cytokines can result in autoimmune responses.

PMID- 9144511
TI  - Inhibition of prostaglandin endoperoxide synthase-2 expression in stimulated
      human monocytes by inhibitors of p38 mitogen-activated protein kinase.
AB  - Prostaglandin endoperoxide synthase (PGHS; cyclooxygenase), the rate-limiting
      enzyme in the conversion of arachidonic acid to prostanoids, has two isoforms.
      PGHS-1 is constitutively expressed and involved in homeostasis, whereas PGHS-2 is
      inducible in monocytes in response to proinflammatory agents. Using freshly
      elutriated human monocytes, we examined the effect on PGHS-2 expression of
      certain cytokine-suppressive anti-inflammatory drugs such as SK&F 86002.
      Incubation with serum-treated zymosan (STZ) stimulated the expression of PGHS-2
      in a time- and dose-dependent manner. SK&F 86002 dose-dependently inhibited this
      STZ-induced expression of PGHS-2 protein, which correlated with a decrease in
      prostaglandin E2 and thromboxane A2 production. However, suppression of PGHS-2
      expression is not the result of suppressed cytokine production, because SK&F
      86002 suppressed PGHS-2 expression initiated by IL-1beta and TNF-alpha, in
      addition to other stimuli. Moreover, this effect was selective in that the
      protein expression of two other important enzymes involved in the metabolism of
      arachidonic acid, cytosolic phospholipase A2 and 5-lipoxygenase, was not
      affected. Stimulation with STZ caused a time-dependent increase in levels of PGHS
      2 mRNA; incubation with cytokine-suppressive agents caused a decrease of these
      levels, suggesting the involvement of transcription and/or mRNA stability events
      in the inhibition of PGHS-2. These results indicate a new and potentially
      important anti-inflammatory property of SK&F 86002, namely the specific
      suppression of PGHS-2 induction.

PMID- 9144512
TI  - The balance between nitric oxide and superoxide determines apoptotic and necrotic
      death of rat mesangial cells.
AB  - Nitric oxide (NO.) and superoxide (O2-) are inflammatory mediators. Their
      formation seems to be associated with apoptotic and/or necrotic cell death in
      diseases such as mesangioproliferative glomerulonephritis in which the early
      phase of mesangiolysis is linked to significant NO. production. Notably,
      mesangial cells (MC) not only generate NO. but also O2- after cytokine
      stimulation. Here we investigated the interrelation between NO. and O2- in MC
      death by generating both radicals with the use of NO donors (S
      nitrosoglutathione, spermine-NO) and O2(-)-generating systems (2,3-dimethoxy-1,4
      naphtoquinone, hypoxanthine/xanthine oxidase). Exogenously supplied NO. or O2- in
      a concentration-dependent manner induced apoptosis and/or necrosis. Apoptosis is
      characterized by chromatin condensation and DNA fragmentation in contrast to
      necrotic cytoplasmatic membrane rupture. Noteworthy, coincubation of NO. and O2-
      was cross-protective. Maximum protection required the existence of a balanced
      NO./O2- ratio. Analysis in cytokine-stimulated MC suggests endogenous radical
      formation, which may participate in modulating apoptosis. Manipulation of the
      endogenous NO./O2- ratio by exogenous, sublethal S-nitrosoglutathione in addition
      to cytokines produced death, which was antagonized by inducible nitric oxide
      synthase (iNOS) inhibition. Moreover, pyrrolidine dithiocarbamate
      supplementation, which down-regulates iNOS expression and blocks superoxide
      dismutase activity, initiates apoptosis. Our results imply the participation of
      reactive nitrogen and oxygen species in determining life and death of MC.

PMID- 9144513
TI  - Adenosine metabolism during phorbol myristate acetate-mediated induction of HL-60
      cell differentiation: changes in expression pattern of adenosine kinase,
      adenosine deaminase, and 5'-nucleotidase.
AB  - Adenosine has potent immunosuppressive activity. Since the source of adenosine
      and the mechanism of its release in the immune system is largely unknown and may
      vary according to cell type, we have evaluated the relationship between adenosine
      metabolism and the enzymatic activities and mRNA levels of adenosine-metabolizing
      enzymes in myeloid and lymphoid cell lines. Induction of HL-60 cell
      differentiation along the macrophage lineage by PMA resulted in a reduction in
      the activities of adenosine deaminase (ADA), adenosine kinase (AK), and inosine
      monophosphate-specific cytosolic 5'-nucleotidase and an elevation of ecto-5'
      nucleotidase (ecto-5'-NT). These changes were accompanied by an elevation of ecto
      5'-NT mRNA and a decrease in ADA and AK mRNAs in a time-dependent fashion.
      Comparison of AK and ADA mRNA levels in several other leukemic cell lines
      revealed generally similar responses to PMA with much stronger suppression in
      immature T cells than in B cells. The metabolism of adenosine either through
      phosphorylation (AK) or deamination (ADA) was reduced in PMA-stimulated cells.
      Furthermore, the cumulative changes in enzyme expression resulted in a 2.5-fold
      increase in intracellular adenosine formation in PMA-stimulated cells. The
      inhibition of AK by 5'-iodotubercidin further increased adenosine formation by 6
      fold over that in untreated cells. In accord with the increase in ecto-5'-NT
      activity, extracellular AMP dephosphorylation increased dramatically, but there
      was no increase in extracellular ATP degradation. These results indicate that a
      coordinated shift in adenosine-metabolizing enzyme levels during PMA-induced HL
      60 cell differentiation is accompanied by a decrease in adenosine uptake and an
      increase in adenosine release.

PMID- 9144514
TI  - Monocyte chemotactic protein-3 (MCP-3)/fibroblast-induced cytokine (FIC) in
      eosinophilic inflammation of the airways and the inhibitory effects of an anti
      MCP-3/FIC antibody.
AB  - Monocyte chemotactic protein-3 (MCP-3)/fibroblast-induced cytokine (FIC), a CC
      chemokine, is chemotactic for cells that typically infiltrate the late-phase
      allergic reaction. We developed a mouse model of airway inflammation to study the
      role of MCP-3/FIC. The immunization of mice with OVA resulted in Ag-specific IgE
      Ab production and the expression of mRNA for IL-4 in the lung tissue. Two weeks
      after immunization mice were challenged with the allergen by inhalation. Lungs
      were lavaged, and the tissue was examined at 2 or 24 h. Allergen challenge
      resulted in the increased recovery of leukocytes in the lavage fluid, but saline
      challenge did not. There was a significant increase in eosinophils (29 +/- 8% vs
      1.2 +/- 0.2%) and lymphocytes (25 +/- 4% vs 5 +/- 2%) in the bronchoaveolar
      lavage fluid. Histologic examination of the lung demonstrated intense airway
      inflammation following OVA challenge. The expression of MCP-3/FIC and other CC
      chemokines (MCP-1, macrophage inflammatory protein-1alpha, and RANTES) was
      investigated by reverse transcription-PCR followed by densitometric analyses. The
      allergen challenge up-regulated the expression of mRNA for MCP-1, MCP-3/FIC, and
      macrophage inflammatory protein-1alpha at 2 and/or 24 h. Immunocytochemical
      staining for MCP-3/FIC showed that the allergen challenge induced the expression
      of MCP-3/FIC predominantly in the airway epithelium. Pretreatment of mice with an
      anti-MCP-3/FIC Ab significantly inhibited the OVA-induced airway inflammation and
      the bronchoalveolar lavage eosinophilia (8 +/- 2% vs 46 +/- 11% after control Ab,
      p < 0.03). We conclude that MCP-3/FIC plays a significant role in the allergen
      induced eosinophilic inflammation of the airways.

PMID- 9144515
TI  - Mitogen-activated protein kinase activation during IgG-dependent phagocytosis in
      human neutrophils: inhibition by ceramide.
AB  - In FMLP-activated polymorphonuclear leukocytes (PMNs) challenged with IgG
      opsonized erythrocytes (EIgG), the termination of phagocytosis correlates with an
      accumulation of ceramide, a product of sphingolipid metabolism. Furthermore, the
      exogenous addition of short chain ceramides inhibits EIgG-mediated phagocytosis.
      In the present study, we identified p42 and p44 mitogen-actived protein (MAP)
      kinases, referred to as extracellular signal-regulated kinases ERK2 and ERK1,
      respectively, as intracellular targets of ceramide action during Fc gammaR
      mediated phagocytosis. The tyrosine phosphorylation of ERK1 and ERK2 increased
      within 30 s of addition of EIgG, with maximal phosphorylation by 1 to 5 min. By
      30 min, ERK1 and ERK2 were almost completely dephosphorylated. The kinetics of
      ERK1 and ERK2 tyrosine phosphorylation indicated that MAP kinase activation
      preceded target ingestion. N-Acetylsphingosine (C2-ceramide) inhibited
      phagocytosis, reduced ERK1 and ERK2 phosphorylation to basal levels, and reduced
      ERK1 and ERK2 activity by 85 to 90% and 70 to 80%, respectively. In contrast, N
      acetyldihydrosphingosine (dihydro-C2-ceramide) had no effect on either tyrosine
      phosphorylation or activity of ERK1 and ERK2. In the presence of the MAP kinase
      kinase (MEK) inhibitor, PD 098059, phagocytosis was reduced by approximately 50%,
      while ERK1 and ERK2 activity was reduced by 85 to 90%. Thus, engagement of Fc
      gammaRs led to ERK1 and ERK2 phosphorylation and activation, and the activation
      of these enzymes was critical for phagocytosis. Furthermore, the inhibition of
      phagocytosis by C2-ceramide correlated with the inhibition of tyrosine
      phosphorylation and activation of ERK1 and ERK2. These results suggest that
      ceramides generated during phagocytosis act on the MAP kinase signaling pathway,
      ultimately "turning off" the phagocytic response.

PMID- 9144516
TI  - Antigen activation of mitogen-activated protein kinase in mast cells through
      protein kinase C-dependent and independent pathways.
AB  - We demonstrate discrete pathways for activation of mitogen-activated protein
      (MAP) kinase in cultured RBL-2H3 mast cells through protein kinase C (PKC),
      cytosolic calcium, and a third pathway that provides sustained signals for
      activation in Ag-stimulated cells. Thus, p42 MAP kinase was activated by
      increasing intracellular free Ca2+ with thapsigargin or by stimulating PKC with
      PMA. The latter stimulation was selectively blocked by the protein kinase C
      inhibitor, Ro31-7549. Stimulation of p42 MAP kinase by Ag resulted in relatively
      sustained activation of MAP kinase which was only partially suppressed by Ro31
      7549. Kinetic studies revealed two components of the MAP kinase response to Ag: a
      rapid but transient component that was Ro31-7549 sensitive and presumably PKC
      dependent; and a more sustained component that was Ro31-7549 resistant and
      presumably PKC independent. Similarly, Ro31-7549 inhibited the early but not late
      release of arachidonic acid, a finding that was consistent with the known
      regulation of phospholipase A2 by MAP kinase. Early tyrosine phosphorylation
      events which were thought to be essential for Ag-induced activation of p42 MAP
      kinase and release of arachidonic acid were unaffected by Ro31-7549. The findings
      suggested that release of arachidonic acid was regulated primarily through MAP
      kinase but that PKC may transiently influence this release, either directly or
      indirectly through MAP kinase.

PMID- 9144517
TI  - Crucial role of CD8-positive lymphocytes in glomerular expression of ICAM-1 and
      cytokines in crescentic glomerulonephritis of WKY rats.
AB  - CD8-positive lymphocytes (CD8+ lym) and ICAM-1/LFA-1 interaction have been
      implicated in the glomerular accumulation of monocytes/macrophages (Mo/Mphi) and
      crescent formation in antiglomerular basement membrane (anti-GBM)
      glomerulonephritis of WKY rats. In the present study, the role of CD8+ lym in the
      expression of ICAM-1 and inflammatory cytokines as well as in the accumulation of
      Mo/Mphi in the glomeruli was examined by RNase protection assay and
      immunofluorescence microscopy. ICAM-1 expression was apparent at 1 h and markedly
      enhanced at day 3 in glomeruli after an anti-GBM Ab injection in parallel with
      glomerular accumulation of Mo/Mphi. Expression of mRNA for IL-1beta, TNF-alpha,
      and IFN-gamma, known to enhance ICAM-1 expression, and MIP-1alpha, MIP-1beta, and
      MCP-1, known to activate leukocyte integrins or to act as chemokines, were also
      induced in the glomeruli at a mRNA level in a profile similar to that of ICAM-1
      expression. By depleting the CD8+ lym in the circulation, the increased
      glomerular expression of ICAM-1 and the cytokines, except IL-1beta, and the
      Mo/Mphi accumulation were suppressed, indicating a crucial role of CD8+ lym in
      the accumulation of Mo/Mphi through stimulation of ICAM-1 and induction of
      cytokines.

PMID- 9144518
TI  - Sezary lineage cells can be induced to proliferate via CD28-mediated
      costimulation.
AB  - Sezary syndrome and mycosis fungoides are related chronic lymphoproliferative
      diseases caused by the malignant growth of CD4+ T lymphocytes that display
      hyperconvoluted nuclei and a predilection for skin homing. Despite the malignant
      nature of these cells, they paradoxically do not grow in vitro, either
      spontaneously or following exposure to mitogens. Partly because of this technical
      limitation, the cellular lineage and causes of abnormal growth resulting in a
      classical hyperconvoluted Sezary cell are poorly characterized. To better
      understand these aspects, we examined Sezary lineage cell growth in vitro. We
      found that, contrary to previous reports, Sezary lineage cells are capable of in
      vitro proliferation in response to either PHA or anti-CD3 mAb, if exogenous
      costimulation is provided. The CD28-B7 interaction provides at least one of the
      costimulatory signals capable of inducing Sezary lineage cell growth. Namely,
      Sezary lineage cells from three of six Sezary syndrome patients proliferated in
      response to PHA if an anti-CD28 mAb was also added to the in vitro culture. The
      remaining three patients' Sezary lineage cells were dependent upon CD28-B7
      mediated costimulation, but in addition required other intercellular signals
      present on blood mononuclear cells. The relative lack of costimulation from the
      patients' own PBMC is not due to an intrinsic defect in the mycosis
      fungoides/Sezary syndrome patients' immune accessory cells. Rather, it appears
      primarily due to an inability of Sezary cells to significantly up-regulate CD40
      ligand (gp39) following in vitro exposure to PHA.

PMID- 9144519
TI  - Vascular endothelial growth factor is a potent angiogenic factor in AIDS
      associated Kaposi's sarcoma-derived spindle cells.
AB  - Angiogenesis is one of the most important features of AIDS-associated Kaposi's
      sarcoma (AIDS-KS). Our studies suggested that spindle-shaped AIDS-KS cells from
      various AIDS-KS lesions play important roles in the development of KS lesions.
      Basic fibroblast growth factor (bFGF) has been reported to be a predominant
      angiogenic factor expressed in AIDS-KS cells. However, our data from ELISA
      revealed the presence of the vascular endothelial growth factor (VEGF) molecule
      in large quantities in AIDS-KS cell-derived conditioned medium (AIDS-KS-CM) (12.1
      21.4 ng/ml). In contrast, small amounts of bFGF were detected in AIDS-KS-CM (76
      245 pg/ml). The combination of anti-VEGF and anti-bFGF IgGs completely inhibited
      endothelial cell growth-promoting activities in AIDS-KS-CM, while activities
      partially remained in the presence of anti-bFGF IgG or anti-VEGF IgG alone. VEGF
      and bFGF in AIDS-KS-CM were distinguished by heparin-affinity chromatography.
      Furthermore, the combination of VEGF and bFGF synergistically augmented the
      growth of endothelial cells. Both VEGF and bFGF revealed an angiogenic property
      that was inhibited by specific Abs, when applied to the rabbit cornea and chicken
      chorioallantoic membrane. On Western blots, anti-VEGF IgG gave two major bands of
      22 and 24 kDa, similar to those of recombinant VEGF165. As detected on Northern
      blots, AIDS-KS cells expressed major 3.9-kb VEGF-specific mRNA. Thus, VEGF, in
      concert with bFGF, may play a crucial role in the angiogenesis of AIDS-KS
      lesions.

PMID- 9144520
TI  - Anti-IL-4 monoclonal antibody prevents antibiotics-induced active fatal
      anaphylaxis.
AB  - We previously reported that anti-IL-4 mAb (11B11) failed to prevent protein
      induced fatal murine anaphylaxis. To investigate the effect of anti-IL-4 on
      hapten-induced anaphylaxis, a model of murine anaphylaxis induced by antibiotics,
      penicillin V (Pen V) and cephalothin (CET), was developed, and the effect of anti
      IL-4 on the anaphylaxis was observed. Pen V and CET induced 100 and 70 to 90%
      fatal reactions, respectively, when C57BL/6 mice were sensitized i.p. with 500
      microg of antibiotic-OVA conjugate with 2 x 10(9) Bordetella pertussis and 1.0 mg
      of alum and challenged i.v. with 100 microg of antibiotic-BSA conjugate 14 days
      later. Serum taken from mice sensitized to Pen V passively sensitized normal mice
      to develop systemic anaphylaxis, and this ability of the serum was abrogated by
      heating at 56 degrees C for 2 h or depletion of IgE, but not IgG, Abs. Thus, the
      antibiotic-induced fatal reaction was an IgE-dependent anaphylactic reaction.
      Administration of anti-IL-4 at the beginning of sensitization completely
      prevented the fatal anaphylactic reactions to both Pen V and CET. This effect of
      anti-IL-4 was associated with its suppressive activity on antibiotic-specific
      serum IgE, but not IgG, levels. More importantly, anti-IL-4 therapy in previously
      sensitized mice was also effective in preventing the fatal reactions and rapidly
      reduced the established IgE levels. This study provides a new animal model of
      hapten-induced anaphylaxis and indicates that blocking of IL-4 activity may be
      beneficial in allergic diseases caused by a variety of haptens in which IgE Abs
      play a major role.

PMID- 9144521
TI  - Corticosteroids inhibit lymphocyte binding to endothelium and intercellular
      adhesion: an additional mechanism for their anti-inflammatory and
      immunosuppressive effect.
AB  - Glucocorticosteroids (GCS) are potent anti-inflammatory and immunosuppressive
      agents widely used in the treatment of many medical conditions, but their
      mechanism of action is not yet fully understood. Some of the anti-inflammatory
      effects of GCS have been attributed to the synthesis of lipocortins, whereas the
      immunosuppressive effects are thought to be mediated through the inhibition of
      several immune functions through a down-regulation of cytokine gene expression.
      Another important mechanism of action of GCS may relate to their ability to
      interfere with the phenomena of adhesion and migration of inflammatory cells. In
      this study, the direct effects of GCS on lymphocyte adhesion capacity in vitro
      were investigated. We demonstrate that GCS inhibit lymphocyte adhesion to
      endothelium through the down-modulation of lymphocyte adhesion molecules. We also
      provide evidence that GCS inhibit cell aggregate formation induced by TCR
      ligation, which directly correlates with the down-modulation of LFA-1 and CD2,
      but not LFA-3 or ICAM-1. Such down-modulation was paralleled by a decrease in the
      steady state mRNA level of LFA-1 and CD2 gene products, which suggests a direct
      GCS control of the expression of these genes. Finally, we show that GCS effects
      are mediated through the GCS receptor, since they can be completely reversed by
      the GCS-R antagonist RU-486. This study supports the concept that some of the
      immunosuppressive and anti-inflammatory effects of GCS are likely to be exerted
      by the inhibition of adhesion-dependent lymphocyte functions.

PMID- 9144522
TI  - Human anti-nuclear ribonucleoprotein antigen autoimmune sera contain a novel
      subset of autoantibodies that stabilizes the molecular interaction of U1RNP-C
      protein with the Sm core proteins.
AB  - Anti-Sm Abs recognize Sm core proteins B'/B, D, E, F, and G, shared by U1, U2, U4
      6, and U5 small nuclear ribonucleoproteins (snRNPs), while anti-nuclear
      ribonucleoprotein Ag (nRNP) Abs recognize the U1 RNP-specific 70K, A, and C
      proteins. However, although the autoimmune response to U1 snRNPs involves all
      components of the particle, not all are recognized equally. For example, all
      human anti-nRNP sera contain Abs against native U1-C, in contrast to their
      absence in MRL/lpr mice. In this study, autoantibody recognition of native U1
      snRNPs was investigated by dissociating the particle into four components (U1
      70K, U1-A, U1-C, and the Sm core particle) using 1 M MgCl2 or ribonuclease
      treatment. As expected, human anti-Sm and MRL/lpr sera immunoprecipitated only
      the Sm core proteins, and human anti-nRNP/Sm sera immunoprecipitated the Sm core
      proteins plus U1-C under both conditions. However, although human anti-nRNP sera
      immunoprecipitated U1-C when U1 snRNPs were dissociated before Ab binding, they
      unexpectedly immunoprecipitated the Sm core proteins when Abs were bound before
      dissociation. This apparent paradox was explained by the stabilizing effects of
      anti-nRNP sera on interactions of U1-C with the Sm core particle. All human anti
      nRNP sera contained high levels of autoantibodies that prevent dissociation of U1
      C from the U1 snRNP. These Abs were absent in MRL/lpr mice. Human autoimmune sera
      may prevent dissociation by recognizing the quaternary structure of the U1-C-Sm
      core protein complex or by altering its conformation. Stabilization of U1 snRNPs
      by autoantibodies could influence Ag processing and presentation, possibly with
      important effects on the development of autoimmunity to U1 snRNPs.

PMID- 9144523
TI  - Evidence of presentation of multiple HIV-1 cytotoxic T lymphocyte epitopes by HLA
      B*3501 molecules that are associated with the accelerated progression of AIDS.
AB  - We recently showed HLA-B35-restricted CTL activity for 10 HIV-1 epitopes in PBL
      from two HIV-1-infected individuals. In the present study, we established CTL
      clones specific for nine of these HIV-1 epitopes to confirm these HLA-B35
      restricted epitopes. The specific CTL clones effectively killed the HLA-B*3501
      positive target cells infected with the HIV-1 vaccinia recombinant virus. These
      results confirmed that nine HIV-1 CTL epitopes are presented by HLA-B*3501
      molecules. The CTL activity specific for four Pol and two Nef epitopes was
      induced in the peptide-stimulated PBL from three or more of seven HIV-1-infected
      individuals, indicating that these six are common epitopes. Eight were considered
      strong epitopes because the specific CTL activity was detected in the cultured
      PBL that was once stimulated with peptides. Thus, the present study excluded the
      possibility that the disability of the presentation of HIV-1 epitopes by HLA-B35
      molecules is associated with the accelerated progression of AIDS in HLA-B35
      positive individuals. Analysis of mutated epitopes found in an HIV-1 type B
      strain using the CTL clones revealed that most mutated epitopes partially or
      markedly affect the recognition of CTL clones. Of 19 mutations that affected
      recognition of the CTL clones, 7 reduced peptide-HLA-B*3501 binding, while 12
      affected TCR recognition. These results indicate that natural mutations of HLA
      B35-restricted HIV-1 CTL epitopes affect the recognition of CTL by mechanisms
      that reduce both peptide binding and TCR recognition.

PMID- 9144524
TI  - Differential infection of CD34+ cell-derived dendritic cells and monocytes with
      lymphocyte-tropic and monocyte-tropic HIV-1 strains.
AB  - Monocytes and dendritic cells are infected by HIV-1 and subsequently produce
      virions that initiate further rounds of infection. Current methods for the
      isolation and study of dendritic cells are hampered by the low frequency of these
      cells and contamination with other cell types. A two-step culture method was
      devised to generate large numbers of either dendritic cells or monocytes from
      fetal liver CD34+ progenitors. CD34+ cells were first expanded with the growth
      factors granulocyte-macrophage CSF and stem cell factor to generate a population
      of intermediate progenitor cells with a relatively immature phenotype. To induce
      specific differentiation to dendritic cells, the cultures were switched to serum
      free medium with the growth factors granulocyte-macrophage CSF, stem cell factor,
      TNF-alpha, and IL-4. The cells became highly positive for HLA class II Ags and
      the dendritic cell marker CD1a. Culture of the intermediate progenitors in serum
      containing medium with macrophage CSF resulted in differentiation to adherent
      monocytes expressing high levels of CD14 with low CD1a expression. The
      intermediate progenitors were permissive for HIV infection by both monocyte- and
      lymphocyte-tropic strains. In contrast, differentiation to monocytes or dendritic
      cells resulted in restricted viral tropism. Dendritic cells efficiently
      replicated the lymphocyte-tropic virus HIV-1MN, but not the monocyte-tropic virus
      HIV-1ADA. As expected, monocytes only supported replication of HIV-1ADA. This two
      step culture method allows for the production of large numbers of monocytes or
      dendritic cells from a common precursor pool for studying the development of
      tropism-associated events.

PMID- 9144525
TI  - The human complement C9 gene: identification of two mutations causing deficiency
      and revision of the gene structure.
AB  - The ninth component of human complement (C9) is the last of the terminal
      complement components creating the membrane attack complex. C9 is a single-chain
      serum protein that is encoded by a gene located on chromosome 5p. Deficiency of
      terminal complement components is generally associated with recurrent neisseria
      infections. We studied a previously described Swiss family with inherited C9
      deficiency. To identify the genetic basis of C9 deficiency, we developed an
      approach using exon-specific PCR and direct DNA sequencing. As a cause of C9
      deficiency, we found two different point mutations, both generating TGA stop
      codons in the coding sequence. One mutation, a C to A exchange, was detected in
      exon 2 at cDNA position 166, the other, a C to T exchange, was located in exon 4
      (cDNA position 464). In family studies of three first-degree relatives with
      heterozygous C9 deficiency, we demonstrated that the two mutations are
      segregating independently. Therefore, these mutations are sufficient to explain
      the complete deficiency of both the probands studied. DNA sequencing of the exon
      intron junctions revealed a number of revisions regarding the boundaries between
      exons 4, 5, and 6 as well as between exons 10 and 11. No additional introns were
      detected in exons 6 and 10. Furthermore, DNA marker studies were conducted using
      known polymorphisms of the C6, C7, and C9 genes, confirming the linkage of the
      observed C9 mutations with defined haplotypes.

PMID- 9144526
TI  - Associations between IL-13 and IL-4 (mRNA and protein), vascular cell adhesion
      molecule-1 expression, and the infiltration of eosinophils, macrophages, and T
      cells in allergen-induced late-phase cutaneous reactions in atopic subjects.
AB  - IL-13, like IL-4, induces up-regulation of vascular cell adhesion molecule-1
      (VCAM-1) expression on human endothelial cells in vitro. This may contribute to
      local accumulation of alpha4beta1+ inflammatory cells, such as eosinophils,
      macrophages, and T cells. We tested the hypothesis that in human allergic
      inflammatory reactions in vivo, IL-13 and IL-4 are both involved in VCAM
      1/alpha4beta1-dependent recruitment of inflammatory cells. Cryostat cutaneous
      sections from 13 atopic subjects taken 6, 24, and 48 h after allergen challenge
      were processed for immunohistochemical staining and in situ hybridization using
      mAbs and 35S-labeled riboprobes for IL-4 and IL-13. When compared with diluent
      sites, allergen provoked significant increases in the numbers of cells that were
      mRNA+ and protein-positive for both IL-13 and IL-4 that were clearly demonstrable
      at 6 h, peaked at 24 h, and declined by 48 h. Double immunohistochemical
      staining/in situ hybridization showed that the majority (>60%) of IL-13 mRNA+
      signals were colocalized to CD3+ T cells. The numbers of mRNA+ and protein
      positive cells for IL-13 significantly correlated with VCAM-1 immunoreactivity on
      endothelial cells and with total numbers of infiltrating EG2+ eosinophils,
      CD45RO+ T cells, and CD68+ macrophages, but not elastase-positive neutrophils, at
      the 6- and 24-h time points. At 6 h, an association was also observed between the
      numbers of IL-4 mRNA+ or protein product-positive cells and VCAM-1 expression,
      although this was not statistically significant. These findings suggest that IL
      13 may play an important role in recruitment of inflammatory cells to the site of
      cutaneous allergic inflammatory reaction through VCAM-1/alpha4beta1-dependent
      mechanisms.

PMID- 9144527
TI  - The presence of the 50-kDa subunit of dynactin complex in the nerve growth cone.
AB  - Membrane proteins in growth cone-enriched and growth cone-non-enriched fractions
      prepared from neonatal mouse brain were separated by lectin-affinity and ion
      exchange chromatographies, 2D-PAGE, and SDS-PAGE. Partial amino acid sequences of
      the proteins concentrated in the growth cone-enriched fraction were determined.
      We found that one such protein, gmp23-48k, corresponds to the 50-kDa subunit
      (p50) of the dynactin complex. An antibody raised against gmp23-48k strongly
      reacted with growth cones of differentiated neuronal precursor cells. Immunoblot
      analyses revealed that gmp23-48k was present both in membrane and in soluble
      fractions of neonatal brain. However, the amount of gmp23-48k in the membrane
      fraction greatly decreased in adult brain. These results suggest a special role
      of membrane-associated gmp23-48k/p50 in synapse formation during brain
      development.

PMID- 9144528
TI  - Rat liver 4S-benzo[a]pyrene-binding protein is distinct from glycine N
      methyltransferase.
AB  - Rat liver 4S-benzo[a]pyrene-binding protein (BAP) was reported to be identical to
      the subunit (Mr 32,500) of the tetrameric glycine N-methyltransferase (GNMT). We
      have reevaluated this study. When a liver cytosol was subjected to Sephacryl S
      200 gel permeation chromatography, enzyme activity as well as cross-reactivity
      with anti-GNMT antibody were found only at the elution position of the purified
      GNMT. Chromatograph of the cytosol pretreated with [3H]benzo[a]pyrene showed two
      peaks in the void volume and at the position of an approximate Mr of 40,000. The
      latter, corresponding to the 4 S BAP, did not cross-react with the anti-GNMT
      antibody. An extract of nuclei in which GNMT was proposed to act as a mediator of
      cytochrome P4501A1 gene expression contained the tetrameric GNMT but no binding
      activity. The lung, in which no GNMT mRNA occurred, had the 4 S BAP. Extracts of
      Escherichia coli and COS-7 cells expressing large amounts of GNMT showed no 4 S
      BAP. These findings suggest that the 4 S BAP is distinct from the subunit of
      GNMT.

PMID- 9144529
TI  - Rapid volume expansion in the Torpedo electric organ associated with its
      postsynaptic potential.
AB  - By electrically stimulating Torpedo electric organs enclosed in a sealed plastic
      chamber, it was demonstrated that the production of a postsynaptic potential is
      accompanied by a rapid increase in the volume of the organ. This increase started
      almost simultaneously with the onset of the postsynaptic potential and reached
      its maximum at about the end of the potential. The volume returned slowly to its
      resting level. Repetitive stimulation produced a summation of volume changes. The
      maximum change evoked by a single electric shock was roughly 10(-6) times the
      electrocyte volume. The thermal expansion of the organ associated with the
      production of a postsynaptic potential accounts for roughly 25% or less of this
      volume increase. The possibility is pointed out that a cation-exchange process
      involving Ca2+ on anionic sites in the electrocyte protoplasm may be at the base
      of the volume changes.

PMID- 9144530
TI  - Structural modifications of interleukin-2 at positions 47 and 65.
AB  - Interleukin-2 (IL-2) is a cytokine essential for the growth and proliferation of
      T-cells. The purpose of this research was to study the effects of altering the
      "kink" caused by Pro in an alpha-helix of the protein. The Pro-47 residue was
      chosen because it was originally, but mistakenly, traced to the kink of an alpha
      helix [1]. Pro-65 is now recognized to be situated in the middle of helix B [2].
      To study the significance of this Pro for the bioactivity and overall
      conformation of IL-2 it was mutated to Gly and Ala. We successfully obtained 17
      different mutants at position 47 and two mutants at position 65. Certain amino
      acid substitutions representing different categories of amino acids, namely,
      acidic, neutral and helix stabilizing, were chosen for more thorough
      investigation. The results showed that Asn-47 and Asp-47 decreased the
      bioactivity of these mutants by 50- and 700-fold respectively, while the Kd to
      its high affinity receptors was increased 180- and 90-fold respectively, compared
      to IL-2. The intermediate binding affinity of Asn-47 and Asp-47 was decreased 8-
      and 37-fold, respectively. On the other hand, Gly-47, Gly-65 and Ala-65 showed
      less dramatic decreases in bioactivity and high affinity binding. The
      intermediate binding affinity of these mutants decreased from 5- to 3-fold and
      low affinity binding decreased approximately 4-fold suggesting some structural
      and conformational changes. From these observations, we conclude that Asn-47 or
      Asp-47 disrupt the hydrophobic packing of the core and thus changed the overall
      conformation of the protein, thereby giving rise to partial agonists. Although
      Pro-65 lies within the helix, it may be near the surface of the protein but may
      not be the actual binding site and thus any conservative mutation can be better
      tolerated.

PMID- 9144531
TI  - A novel 90-kDa stress protein induced in fish cells by fish rhabdovirus
      infection.
AB  - A 90 kDa cellular protein in a fish cell, CHSE-214, showed increased expression
      by the infection of infectious hematopoietic necrosis virus (IHNV), heat shock, 2
      mercaptoethanol, copper sulfate, and cadmium sulfate, and was detected in various
      kinds of cells such as human, rat, and mouse cells. The molecular mass of the 90
      kDa protein was different from those of the hsp90 and grp94. In addition, all the
      anti-stress protein MAbs did not react with the 90 kDa protein. Finally, the
      subcellular distribution of the 90 kDa protein, determined by Western blots of
      subcellular fractions, was found to be mainly nuclear, both in normal and IHNV
      infected CHSE-214 cells. The present results indicate that the 90 kDa protein is
      a kind of stress protein. However, based on its molecular mass, antigenic
      characteristics, and subcellular distribution, it is likely that this protein is
      a novel stress protein that has not been previously described in animal systems,
      especially in fish systems.

PMID- 9144532
TI  - Differential expression of PPAR gamma1 and gamma2 isoforms in human adipose
      tissue.
AB  - One of the essential factors for adipogenesis, peroxisome proliferator activated
      receptor gamma (PPAR gamma), is classified into two isoforms, gamma1 and gamma2
      encoded by a single PPAR gamma gene. To examine the mode of expressions of both
      the PPAR gamma1 and gamma2 isoforms in human adipose tissue, we cloned a partial
      cDNA of the human PPAR gamma2 (hPPAR gamma2) from a human adipose tissue cDNA
      library. The sequence encoded an additional 28 amino acids amino-terminal to the
      first ATG codon of hPPAR gamma1. The simultaneous quantitation of hPPAR gamma1
      and gamma2 mRNA in subcutaneous or visceral (mesenteric) fat tissue from 10
      different individuals was performed by an RNase protection assay and revealed a
      relatively higher expression of gamma1 than gamma2 in all specimens examined.

PMID- 9144533
TI  - Purification of the putative coxsackievirus B receptor from HeLa cells.
AB  - We have identified a protein expressed by human and murine cells susceptible to
      coxsackievirus B3 (CVB3) infection and purified it from HeLa cells. This protein
      of approximately 45,000 Mr is expressed by HeLa cells and mouse fetal heart
      fibroblasts (susceptible to infection), and not by C3H murine fibroblasts or the
      human RD cell line (resistant). The protein was isolated from Triton X-100-
      deoxycholate lysates of HeLa cells by chromatography on concanavalin A-Sepharose,
      Affi-gel Blue, Phenyl Sepharose, and PBE94. The CVB3-binding fraction from PBE94
      was blotted from SDS-polyacrylamide gel onto PVDF membrane for amino acid
      sequencing. Approximately 2 pmoles of CVB3-binding protein provided assignments
      for 26 consecutive residues: LSITTPEEMIEKAKGETAYLPXKFTL. This sequence
      corresponds neither to decay accelerating factor nor to nucleolin, both of which
      have previously been identified as CVB3-binding proteins, but does match two
      entries in GenBank. These data show that we have purified a novel CVB3-binding
      protein, the characteristics of which suggest the CVB group receptor has been
      purified. Identification of 26 amino acid residues in the protein and
      corresponding GenBank enteries will accelerate study of CVB tropism and the
      diseases caused by these viruses.

PMID- 9144534
TI  - Functional expression of human p21(WAF1/CIP1) gene in rat glioma cells suppresses
      tumor growth in vivo and induces radiosensitivity.
AB  - This study reports the successful growth suppression of a rat glioblastoma model
      (RT-2) both in vitro and in vivo by the insertion of p21(WAF1/CIP1), a negative
      cell cycle regulatory gene, into the tumor cells. Greater than 95% of the tumor
      cells expressed p21 protein after being infected with pCL based p21 retrovirus at
      4x M.O.I. (multiplicity of infection). The p21-infected cells showed a 91%
      reduction in colony forming efficiency and a 66% reduction in growth rate. More
      prominent p21 staining was found in cells exhibiting histologic evidence of
      senescence. Intracranial implantation of the infected cells showed complete
      disappearance of the p21-infected cells at day 10 and long-term survival of the
      animals compared to controls. Injection of pCLp21 virus into tumor established in
      situ showed tumor necrosis and gene expression. In a clonogenic radiation
      survival assay, a 93% reduction of surviving colonies of p21-infected cells was
      seen in comparison to vector-infected control cells and to p53-infected cells
      after exposure to 8 Gy (800 rads).

PMID- 9144535
TI  - A novel G protein-coupled receptor with homology to neuropeptide and
      chemoattractant receptors expressed during bone development.
AB  - A novel G protein-coupled receptor was isolated from a cDNA derived from the cell
      line NH15-CA2 and a cDNA library from adult mouse brain using a PCR cloning
      strategy. The amino acid sequence of the candidate receptor DEZ showed homology
      to neuropeptide and chemoattractant receptors. Highest overall homology was found
      with the orphan receptor GPR-1 (65%), the angiotensin II receptor (62%), and the
      C5a anaphylatoxin receptor (60%). Northern blot analysis of dez revealed a
      predominant 2.6 kb mRNA species in NH15-CA2 cells. In situ hybridization
      experiments showed that dez is differentially regulated during development, with
      a prominent expression in developing osseous and cartilaginous tissue. It was
      also detectable in the adult parathyroid glands, hinting at a possible function
      in bone metabolism.

PMID- 9144536
TI  - Specific cleavage of the large subunit of replication factor C in apoptosis is
      mediated by CPP32-like protease.
AB  - Recent evidence suggests that the growing family of cysteine proteases related to
      the interleukin-1beta-converting enzyme (ICE) is of central importance in
      mediating apoptosis. Proteolytic cleavage of a small group of cellular substrates
      by these enzymes in association with the onset of apoptosis has been reported. In
      the present study, we searched a protein data base for potential death substrates
      possessing the CPP32 cleavage site, DEVD, and identified several candidates
      including RFC140, the large subunit of replication factor C, which we
      subsequently demonstrated to be specifically cleaved in a variety of cell types
      undergoing apoptosis in response to different cytotoxic agents, whereas no
      degradation is observed in a cell line resistant to etoposide-induced apoptosis.
      The abrogation of RFC140 cleavage in apoptotic extracts by Ac-DEVD-CHO, a potent
      inhibitor of CPP32, together with the finding that a CPP32 consensus cleavage
      sequence, DEVD, exists in RFC140, suggests that CPP32 or a close relative is
      responsible for RFC140 degradation in apoptosis.

PMID- 9144537
TI  - The use of Renilla luciferase, Oplophorus luciferase, and apoaequorin as
      bioluminescent reporter protein in the presence of coelenterazine analogues as
      substrate.
AB  - To investigate the use of various luciferases as reporter protein, the substrate
      specificity of recombinant Renilla luciferase, Oplophorus luciferase and
      recombinant apoaequorin was examined using 23 kinds of coelenterazine analogues
      as the substrate. The intensity of luminescence was generally highest with
      Oplophorus luciferase and lowest with apoaequorin, but varied widely by the
      substrate used. A very high level of light intensity was obtained when the
      luminescence reactions of e-coelenterazine and v-coelenterazine were catalyzed by
      Renilla luciferase, strongly suggesting the usefulness of recombinant Renilla
      luciferase as a highly sensitive reporter protein. Oplophorus luciferase can be
      an equally sensitive reporter protein when its gene is obtained.

PMID- 9144538
TI  - Purification and characterization of the precursor tRNA 3'-end processing
      nuclease from Aspergillus nidulans.
AB  - The precursor-tRNA 3'-end processing nuclease activity was purified homogeneously
      about 15,300 fold from the heat-treated fraction. The precursor-tRNA 3'-end
      processing nuclease was a single polypeptide of 160,000 Da. This nuclease
      generates a mature 3'-end of nuclear tRNA(Asp) of Aspergillus nidulans by the
      endonuclease activity and prefers the 5'-end processed tRNA(Asp) rather than
      primary precursor-tRNA(Asp) as a substrate. However, this enzyme did not process
      both primary mitochondrial precursor-tRNA(His) and 5'-end processed mitochondrial
      precursor-tRNA(His) of A. nidulans.

PMID- 9144539
TI  - Intracavitary liposome-mediated p53 gene transfer into glioblastoma with
      endogenous wild-type p53 in vivo results in tumor suppression and long-term
      survival.
AB  - A cavitary glioblastoma model was created by injection of RT-2 cells, which
      express endogenous wild type p53, into the peritoneal cavity of nude mice. This
      model developed multiple layers of tumor cells invading the peritoneal surface
      and was used to mimic the postoperative surgical cavity remaining after
      glioblastoma (GBM) excision in patients. Rhodamine labeled DMRIE/DOPE + DNA
      complexes were found to penetrate at least 20 tumor cell layers. Injection of p53
      gene/liposome complexes into the intraperitoneal cavity after the tumor was
      established resulted in massive tumor necrosis. Prominent staining of human p53
      protein using the DO-1 antibody was found in tumor cells near the necrotic
      lesions. Tumor explants expressed human p53 protein and showed a 54% growth
      reduction in an in vitro growth assay. Further, DMRIE/DOPE mediated p53 gene
      transfection significantly increased the mean survival time of tumor bearing mice
      compared to vector control. These results demonstrate the efficiency of using
      exogenous wild type p53 to suppress glioblastoma cell with endogenous wild type
      p53 in vivo through liposome mediated transfection method.

PMID- 9144540
TI  - Cell-type-specific modulation of Hox gene expression by members of the TGF-beta
      superfamily: a comparison between human osteosarcoma and neuroblastoma cell
      lines.
AB  - Homeobox gene expression in osteoblast-like cells was investigated using the
      polymerase chain reaction (PCR). A total of 13 homeobox genes was detected in U-2
      OS (human osteosarcoma) and MC3T3-E1 (mouse osteoblast) cells by sequencing
      cloned PCR products. Using specific primers, a different pattern of Hox gene
      expression was shown for the neuroblastoma cell line SK-N-SH relative to U-2 OS
      and MC3T3-E1. Additionally, we showed that expression of HOXC6 in U-2 OS and SK-N
      SH was differentially regulated by rhBMP-2, TGF-beta and activin-A. This suggests
      that specific Hox genes may be target genes for TGF-beta superfamily members, and
      allows us to further understand the complex functions of these growth factors and
      how they relate to growth and development.

PMID- 9144541
TI  - Phosducin and betagamma-transducin interaction I: effects of post-translational
      modifications.
AB  - The interaction between phosducin and betagamma-transducin plays regulatory roles
      in light adaptation of photoreceptors. Both phosducin and betagamma-transducin
      undergo post-translational modifications, with phosducin modified by
      phosphorylation and the gamma subunit of betagamma-transducin by farnesylation
      and carboxylmethylation. In this study we exploited the electrophoretic
      mobilities of these native proteins to develop a micro binding assay and examined
      the effects of post-translational modifications on binding affinities. It was
      found that decarboxylmethylation of gamma-transducin increased the mobility of
      betagamma-transducin during native gel electrophoresis, but decreased the
      apparent affinity for phosducin by about 2-fold. Phosphorylation of phosducin by
      protein kinase A increased the mobility but decreased the apparent affinity for
      betagamma-transducin by at least 3-fold.

PMID- 9144542
TI  - Induction of NO synthesis by lipoteichoic acid from Staphylococcus aureus in J774
      macrophages: involvement of a CD14-dependent pathway.
AB  - Lipoteichoic acid (LTA), a wall fragment of gram-positive bacteria, induces an
      isoform of NO synthase (iNOS) in vascular smooth muscle cells and macrophages
      which produces large quantities of NO and profound vasodilation in rats; this
      process may be involved in the cause of gram-positive septic shock. This study
      investigates the effect of LTA from Staphylococcus aureus on NO synthesis and
      iNOS mRNA induction in a mouse macrophage cell line (J774). LTA caused a time-
      and dose-dependent increase in NO production and a marked induction of iNOS mRNA.
      The induction of NO synthesis and iNOS gene expression in response to LTA was
      significantly inhibited by an anti-mouse CD14 monoclonal antibody. Studies
      utilizing a mutant cell line (J7.DEF3), which is defective in the expression of a
      CD14 antigen, showed that the increase in NO and iNOS mRNA caused by LTA is
      profoundly depressed in J7.DEF3 cells compared to that in parent J774 cells. In
      contrast, interferon-gamma produced a similar concentration-dependent increase in
      NO formation in both cell types. Thus, CD14 is involved in the signal
      transduction events leading to the enhanced expression of iNOS mRNA and activity
      elicited by LTA in murine macrophages. We propose that agents which block CD14
      dependent events may be useful therapeutics in gram-positive shock.

PMID- 9144543
TI  - Transcription and processing of the gene for spinach chloroplast threonine tRNA
      in a homologous in vitro system.
AB  - An in vitro system was established to study the transcription and processing of
      threonine tRNA using spinach chloroplast enzyme extract. Experiments using a
      series of 5' deletion mutants demonstrated that the transcription of trnT gene
      required no 5' upstream promoter elements. Four plasmid DNA templates containing
      trnT were constructed for tRNA processing assay. The processing reaction was
      carried out either with exogenously added precursor-tRNAs made by T7 RNA
      polymerase or with RNAs synthesized by the transcription activity in the same
      processing enzyme extract. Both assays demonstrated that the 5' and 3' ends of
      mature tRNA were processed endonucleolytically and the processing of the 5' end
      preceded the maturation of the 3' end. The activity of nucleotidyl transferase
      that adds CCA nucleotides to the 3' end of tRNA was also observed. The use of a
      coupled transcription and processing system provides us with a better insight to
      the tRNA processing mechanism of the chloroplast.

PMID- 9144544
TI  - Inhibition of rabbit muscle adenylate kinase by vitamin C.
AB  - Rabbit muscle adenylate kinase (EC 2.7.4.3) is completely inhibited, or nearly
      so, at 2 mM ascorbate, concentrations that are found in tissues. Kinetically, the
      inhibitions show classic non-competitive inhibition patterns against both
      substrates. Ascorbate inhibitions reverse completely in the presence of low
      concentrations of sulfhydryl compounds, such as mercaptoethanol, dithiothreitol,
      cysteine and glutathione. Dehydroascorbate inhibition is relatively poor and is
      also reversed by sulfhydryl compounds. Examination of the adenylate kinase
      inhibited by ascorbate with CD methodology showed no significant change in alpha
      helix and beta-pleated sheet composition.

PMID- 9144545
TI  - ERK and p38 MAP kinase pathways are mediators of intestinal epithelial wound
      induced signal transduction.
AB  - Repair of gastrointestinal epithelial injury involves cell migration,
      proliferation, and specific gene expression. The pathways responsible for
      epithelial wound signal transduction are poorly understood. Mechanical wounding
      of IEC-6 cell monolayers resulted in rapid activation of the extracellular signal
      regulated kinase (ERK) and p38 MAP kinase pathways, while c-Jun amino-terminal
      protein kinases were not significantly activated. Two minutes after wounding
      cells at the wound edge strongly expressed cytoplasmic phospho-ERK. By five
      minutes, immunostaining was concentrated within the nucleus. Consistent with
      activated MAP kinase signaling cascades (which phosphorylate transcription
      factors implicated in immediate-early gene induction), monolayer wounding
      resulted in greater than 30- and 8-fold increases in c-Fos and early growth
      response-1 mRNA by Northern blot analysis, peaking at 20 minutes. Only slight
      increases in c-Jun mRNA were detected. Thus, intestinal epithelial wound signal
      transduction is, at least in part, mediated by activation of ERK and p38 MAP
      kinase signaling cascades. ERK and p38 pathways may regulate pathophysiologically
      relevant genes in wound repair by the induction of transcription factors.

PMID- 9144547
TI  - RNase H activity of human hepatitis B virus polymerase expressed in Escherichia
      coli.
AB  - Human Hepatitis B Virus (HBV) replication is accomplished by its own polymerase.
      The HBV RNase H domain of HBV polymerase has been expressed in Escherichia coli
      and purified by affinity column chromatography. The MBP-RNase H fusion protein
      (43 kDa MBP plus 17 kDa HBV RNase H domain) was proved to be RNase H by in vitro
      activity assay, inhibitor studies, and mutagenesis. The HBV RNase H domain
      represented the optimal RNase H activity in the presence of either 8 mM MgCl2 or
      16 mM MnCl2. In Tris-Cl buffer, the optimum pH for MBP-RNase H fusion protein is
      between 7.7 and 8.2. The MBP-RNase H fusion protein required 40 mM monovalent
      cation for its enzyme activity, whereas it showed lower activity at a salt
      concentration of more than 100 mM. Ribonucleoside Vanadyl complex (RAV) and 2'
      deoxyadenosine 5'-monophosphate (dAMP) inhibited the RNase H activity. Moreover,
      the mutation of highly conserved amino acids in the HBV RNase H domain diminished
      the RNase H activity. These results clearly suggest that the RNase H activity is
      separable from viral HBV polymerase enzymatic activities.

PMID- 9144546
TI  - Cellular mechanism of substance P in the regulation of corticosteroid secretion
      by newt adrenal gland.
AB  - In this work, we have studied the effects and the possible cellular mechanism of
      Substance P (SP) on corticosteroid secretion by the adrenal gland of the urodele
      crested newt, Triturus carnifex. Adrenals were in vitro superfused with SP,
      prostaglandin E2 (PGE2), nitric oxide (NO) donor, cyclic GMP (cGMP) analogue, and
      inhibitors of phospholipase A1, phospholipase A2 (PLA2), phospholipase C,
      adenylate cyclase (AC), cyclooxygenase (COX), NO synthase (NOS), and soluble
      guanylate cyclase (sGC). PGE2, corticosterone, and aldosterone release and NOS
      activity were determined. SP, PGE2, NO donor, and cGMP analogue increased
      corticosterone and aldosterone; SP and PGE2 increased NOS, and SP increased PGE2.
      PLA2, AC, COX, NOS, and sGC inhibitors counteracted SP and PGE2 effects, except
      for PLA2, which did not affect PGE2. These results suggest that SP exhibits a
      stimulatory role on the corticosteroidogenesis of T. carnifex adrenal gland. In
      particular SP enhances PLA2 activity, increasing PGE2; this prostaglandin affects
      AC, which, in turn, enhances NO, and the latter therefore affects sGC, with the
      consequent corticosteroidogenesis increase.

PMID- 9144548
TI  - AIDS-associated Kaposi's sarcoma cells secrete a neurotrophic growth factor(s).
AB  - Here we treat neuronal cells with AIDS-Kaposi's sarcoma cell conditioned medium
      (A-KSCM) in order to determine if AIDS-Kaposi's sarcoma (A-KS) cells secrete
      neurotrophic factors. PC12 and NG108-15 cells were differentiated and allowed to
      form neuronal processes. Under these conditions and in the presence of A-KSCM,
      PC12 cells exhibited more than a twofold increase in the number of branches per
      process and a 40% increase in the number of processes per cell. For NG108-15
      cells, A-KSCM treatment resulted in a three-fold increase in the number of
      branches per process and nearly a twofold increase in the number of processes per
      cell. A-KS cells secrete at least seven known growth factors; however, when
      tested, none of these growth factors mimicked the effect of A-KSCM on neuronal
      cell processes. Therefore A-KS cells secrete a neurotrophic factor(s) which
      remains to be identified and may play a critical role in the progression of A-KS.

PMID- 9144550
TI  - Regulation of p56(lck) messenger turnover upon T cell activation: involvement of
      the 3' untranslated region in stability as determined in cell-free extracts.
AB  - Full activation of T lymphocytes transiently downregulates the steady state level
      of the tyrosine kinase p56(lck) mRNA. Here, we show that a decrease in messenger
      stability is involved in this downmodulation followed thereafter by a rapid and
      marked increase in mRNA half-life. In order to facilitate the study of p56(lck)
      messenger stability, an in vitro mRNA decay assay was developed and used to
      determine whether the 451 nucleotide long 3' untranslated region (3'UTR) of the
      messenger is implicated in the regulation of mRNA stability. Indeed, deletion of
      most of the 3'UTR led to a substantial increase in transcript half-life whereas
      deletion of a limited 3' portion did not, thus showing that the 146 nucleotides
      located in 5' of the 3'UTR contain destabilizing elements. Furthermore, the
      stability of both truncated transcripts was still modulated upon activation,
      thereby suggesting that the activation-responsive elements are located in a
      region distinct from the 3'UTR.

PMID- 9144549
TI  - Two-dimensional millisecond analysis of intracellular Ca2+ sparks in cardiac
      myocytes by rapid scanning confocal microscopy: increase in amplitude by
      isoproterenol.
AB  - Two dimensional images of myocardial Ca2+ sparks, non-propagating local rises in
      cytoplasmic Ca2+ concentration, were obtained at 4 msec intervals with a rapid
      scanning confocal laser microscope, Nikon RCM 8000, and fluo-3. Spontaneous Ca2+
      sparks were observed at apparently random sites throughout the cytoplasm of rat
      ventricular cells. The duration of sparks was 30 to 40 msec and the time to peak
      intensity about 10 msec. Ryanodine (1 microM) completely inhibited Ca2+ sparks
      while nicardipine (3 microM) had no effect. Isoproterenol (1 microM) had no
      effect on the frequency and distribution of Ca2+ sparks but significantly
      increased their amplitude. These results suggest that myocardial Ca2+ sparks are
      the result of spontaneous release of Ca2+ from the sarcoplasmic reticulum and
      that beta-adrenergic stimulation may result in functional modification of the
      ryanodine receptor channel.

PMID- 9144551
TI  - Correlation in HeLa cells of anchorage-independent growth and synthesis of the
      glycoprotein hormone alpha-subunit.
AB  - In addition to its normal synthesis in pituitary and placenta for production of
      the four glycoprotein hormones (GPH), the free alpha-subunit is produced by a
      variety of tumors and tumor-derived cell lines. It has long been used clinically
      as a tumor marker, but the question remains as to whether ectopic production of
      GPH alpha represents the random and chance activation of the hormone gene during
      cancer development or whether GPH alpha may contribute directly or indirectly to
      the biology of the tumor. One characteristic of tumorigenic cells in culture is
      their ability to proliferate in an anchorage-independent way. Data are presented
      in the following paper to show that the cloning efficiency of HeLa cervical
      carcinoma cells in soft agar is directly correlated with their production of the
      GPH alpha-subunit. HeLa variants that differ over 400-fold in their production of
      GPH alpha similarly exhibited a marked difference in their ability to form
      colonies in 0.3% noble agar. When HeLa SR3 cells (a variant that produces GPH
      alpha at high levels) was stably transfected with a vector producing the
      antisense strand of GPH alpha cDNA, the synthesis of the GPH alpha-subunit was
      reduced in these cells as was their cloning efficiency in soft agar. Similarly,
      when HeLa A5F cells (a variant producing little or no GPH alpha) were stably
      transfected with an alpha-subunit expression vector, the production of GPH alpha
      was increased significantly in concert with an increased ability to form colonies
      in 0.3% noble agar. Somatic cell hybrids between HeLa SR3 and HeLa A5F exhibited
      intermediate levels of GPH alpha gene expression and colony formation in soft
      agar compared to the parental strains. These data suggest that some parameters of
      the tumorigenic phenotype, such as anchorage-independent growth, are responsive
      to, or are dependent upon, the production of free alpha-subunit.

PMID- 9144552
TI  - Glycosyl-phosphatidylinositol-phospholipase type D: a possible candidate for the
      generation of second messengers.
AB  - Membrane associated glycosyl-phosphatidylinositols have been shown to be the
      precursors of inositol phosphoglycan second messengers. Extraction of human liver
      membranes and purification by serial thin layer chromatography revealed three
      glycolipids which co-migrated with glycosyl-phosphatidylinositol from rat liver.
      These lipidic fractions were partially sensitive to treatment with nitrous acid
      and to hydrolysis by glycosyl-phosphatidylinositol-specific phospholipase D from
      bovine serum. In parallel, glycosyl-phosphatidylinositol isolated from rat liver
      was found to be a substrate for the enzyme generating a biologically active
      inositol phosphoglycan species (determined by measuring inhibition of protein
      kinase A activity and stimulation of cell proliferation within the chicken embryo
      cochleovestibular ganglion). This molecule was recognised by an anti-inositol
      phosphoglycan antibody. Hence, we propose that glycosyl-phosphatidylinositol
      specific phospholipase D could be implicated in cellular signalling.

PMID- 9144553
TI  - Metabolites produced during the peroxisomal beta-oxidation of linoleate and
      arachidonate move to microsomes for conversion back to linoleate.
AB  - When [1-(14)C]4,7,10-16:3, a product produced after two cycles of arachidonate
      beta-oxidation, was incubated with rat liver peroxisomes and microsomes it was
      metabolized to 2-trans-4,7,10-16:4, a catabolic product; 6,9,12-18:3 and 8,11,14
      20:3, anabolic products made via microsomal chain elongation of the substrate;
      and 7,10-16:2 and 9,12-18:2. Analysis of the acyl-CoAs produced when 6,9,12-18:3
      and its catabolic product, 4,7,10-16:3, where incubated under the above
      conditions showed that the acyl-CoAs of all of the above compounds, as well as
      5,8-14:2-CoA and 6:0-CoA accumulated. Our results show that when 5,8-14:2 and
      4,7,10-16:3 are produced by peroxisomal beta-oxidation they can be further
      degraded to hexanoyl-CoA or move to microsomes for conversion back to linoleate,
      which is a precursor of arachidonate.

PMID- 9144554
TI  - Inhibition of ecto-ATPase by the P2 purinoceptor agonists, ATPgammaS, alpha,beta
      methylene-ATP, and AMP-PNP, in endothelial cells.
AB  - Ecto-ATPase is a plasma membrane-bound enzyme that sequentially dephosphorylates
      extracellular nucleotides such as ATP. This breakdown of ATP and other
      nucleotides makes it difficult to characterize and classify P2 purinoceptors. We
      have previously shown that the P2 purinergic antagonists, PPADS, suramin and
      reactive blue, act as ecto-ATPase inhibitors in various cell lines. Here, we show
      that the P2 purinergic agonists, ATPgammaS, alpha,beta-methylene ATP (alpha,beta
      MeATP) and AMP-PNP, inhibit the ecto-ATPase of bovine pulmonary artery
      endothelial cells (CPAE), with pIC50 values of 5.2, 4.5 and 4.0, respectively. In
      CPAE, FPL67156, a selective ecto-ATPase inhibitor, also inhibits ecto-ATPase
      activity, with a pIC50 value of 4.0. In addition, alpha,beta-MeATP (3-100
      microM), which itself does not induce phosphoinositide (PI) turnover, left
      shifted the agonist-concentration effect (E/[A]) curves for ATP, 2MeS-ATP and UTP
      by approximate 100-300 fold, while those for ATPgammaS and AMP-PNP were only
      shifted approximately 2-3 fold. Moreover, in the presence of alpha,beta-MeATP,
      not only was the potentiation effect of PPADS on the UTP response lost, but a
      slight inhibition of the UTP response by PPADS was also seen. Thus, we conclude
      that the action of ATPgammaS, alpha,beta-MeATP and AMP-PNP as ecto-ATPase
      inhibitors account for their high agonist potency, and also provide information
      for the development of ecto-ATPase inhibitors of high selectivity and potency.

PMID- 9144556
TI  - A deficiency in respiratory complex I in heart mitochondria from vitamin A
      deficient rats is counteracted by an increase in coenzyme Q.
AB  - Defects of NADH:coenzyme Q oxidoreductase (complex I) of mitochondria have been
      described in many congenital and acquired diseases. Administration of coenzyme Q
      (CoQ, ubiquinone) has been shown to benefit patients with some of these diseases.
      However, the mechanisms by which CoQ exerts the therapeutic effects are not
      clearly understood. A reason could be the lack of saturation of CoQ, in kinetic
      terms, for complex I activity. However, this hypothesis has not been proved in
      vivo because of the difficulty to incorporate CoQ into the mitochondrial
      membranes. We have found a deficiency in respiratory complex I in heart
      mitochondria from vitamin A-deficient rats which was accompanied by high CoQ
      content. The defect in complex I activity was compensated by the increase in CoQ
      to maintain the mitochondrial electron transfer rate. This finding supports, for
      the first time in an in vivo experimental approach, the kinetic hypothesis to
      explain the short-term therapeutic effects of CoQ.

PMID- 9144555
TI  - Pterin-6-aldehyde, an inhibitor of xanthine oxidase, has superoxide anion radical
      scavenging activity.
AB  - Superoxide anion radical (O2.-) scavenging activity of neopterin (NP) and its
      photodegraded products was studied. NP did not affect O2.- release in
      hypoxanthine/xanthine oxidase (HPX/XOD) reaction system, but pterin-6-aldehyde
      (P6A), one of photodegraded products of NP, suppressed it. The identification of
      P6A was successful by confirming inhibiting property of xanthine oxidase. In
      neutrophil/phorbol myristate acetate reaction system, NP did not affect the O2.-
      release but P6A suppressed it. The suppression by P6A was not associated with
      oxygen uptake, which indicated that P6A did not inhibit the generation of O2.-
      but directly scavenged it. These findings suggest that P6A has ameliorating
      effects on ischemic-reperfusion injury in which O2.-, which is generated both in
      HPX/XOD reaction and in activated neutrophil, is one of the major substances to
      damage the tissues.

PMID- 9144557
TI  - Expression of rac1 protein in the crypt-villus axis of rat small intestine: in
      reference to insulin action.
AB  - The expression of rho family along the crypt-villus axis of rat small intestine
      was investigated. The immunoblot analysis showed that the content of rac1 protein
      gradually increased from tip-villus to crypt-villus enterocytes without changes
      in the contents of rhoA and rac2 proteins. Furthermore, the contents of rac1
      protein in the entire enterocytes were markedly decreased in streptozotocin
      induced diabetic rats and restored by short-term treatment with insulin. These
      results suggest that differentiation and proliferation in the enterocytes of rat
      small intestine are possibly related to the expression of rac1 protein through
      insulin action.

PMID- 9144558
TI  - cDNA cloning and expression analysis of NeuroD mRNA in human retina.
AB  - We have shown that bHLH proteins are involved in mammalian retinal development.
      Here we report the identification and analysis of the expression of a neurogenic
      differentiation gene, NeuroD, in human retina. In situ hybridization and
      immunocytochemical analyses of adult retina showed that NeuroD transcripts and
      NeuroD immunoreactivity are predominantly localized to the outer nuclear layer
      which contains the photoreceptors. Southern analysis of PCR-amplified cDNA
      revealed that NeuroD mRNA is also expressed in fetal human retina. Fetal monkey
      retina was used to analyse the spatial distribution of NeuroD in the developing
      retina. Both NeuroD transcripts and immunoreactivity are largely detected in the
      outer neuroblastic layer. Therefore, NeuroD may be involved in the
      differentiation as well as maintenance of the differentiated properties of
      photoreceptors.

PMID- 9144559
TI  - Regulation by cAMP of STAT1 activation in hepatic stellate cells.
AB  - Previously we reported that dibutyryl cAMP and phosphodiesterase inhibitor
      methylxanthines block rat stellate cell proliferation. To analyze the underlying
      mechanism, modulation by these agents of platelet-derived growth factor (PDGF)/BB
      stimulating signal pathway was studied. Without reducing STAT1 protein level,
      these agents were found to attenuate STAT1 activation in stellate cells
      stimulated with PDGF/BB as revealed by an electrophoretic mobility shift assay.
      Inhibitory effect started 12 h after exposure of the cells to these agents at
      concentrations of more than 100 microM. These agents had no effects on DNA
      binding activity of STAT1 that had already been activated. Treatment with these
      agents failed to affect the function of PDGF receptors except for partial
      attenuation of phospholipase C activation under PDGF/BB stimulation. The present
      results indicate that inhibition of STAT1 activation may be one of factors
      involved in the cAMP-dependent stellate cell growth arrest.

PMID- 9144560
TI  - The IRI release from insulin gene-transduced hepatic cells responds to ambient
      glucose concentration.
AB  - Insulin gene was induced into differentiated hepatic cell line. These cells
      released immunoreactive insulin (IRI) of which molecular weight was greater than
      mature insulin. The secretion of IRI was responsive to glucose concentration and
      inhibited by glucose metabolism antagonist, 2-deoxy glucose (2-DOG). The mRNA of
      GLUT2 and glucokinase (GK) were not detected in these cells by Northern blotting.
      The glucose metabolism process is supposed to play an important role in the
      glucose responsive IRI release. It is assumed that hepatic cells have metabolic
      "glucose sensor", and insulin gene transduction to hepatic cells can be a
      physiological way of gene therapy for IDDM.

PMID- 9144561
TI  - Machado-Joseph disease gene product identified in lymphocytes and brain.
AB  - Machado-Joseph disease (MJD) is associated with the expansion of an unstable CAG
      repeat. The existence of an abnormal gene product in MJD was previously suggested
      with the expanded polyglutamine stretch-specific antibody. However, the product
      of the normal allele has not previously been identified. We generated monoclonal
      antibodies against the fusion protein (codon 225-310) of the MJD gene product and
      then identified the MJD1 gene product in normal lymphoblastoid cells as a
      approximately 50-kDa protein by immunoblot analysis. The electrophoretic mobility
      differences among the normal allele products corresponds to the molecular size
      difference produced by the polyglutamine stretch and the polymorphism at the C
      terminus. Moreover, abnormal immunoreactive bands which were larger than the
      normal ones were found as a approximately 60-kDa protein exclusively in the MJD
      samples. The cytoplasm and the nuclei of neurons and glial cells were stained by
      these antibodies with immunocytochemistry. As in other CAG repeat diseases, the
      abnormal and normal allele products were almost equally expressed in
      lymphoblastoid cells and the brain of MJD patients.

PMID- 9144562
TI  - Phase-specific protein expression in the dimorphic yeast Saccharomyces
      cerevisiae.
AB  - In oxygen-limited continuous culture, Saccharomyces cerevisiae formed
      pseudohyphae by unipolar budding. We developed a continuous cultivation sequence
      to discriminate phase-specific from metabolically regulated proteins during
      dimorphism. Computer-aided substractive analysis of 2D-PAGE protein patterns
      allowed the detection of proteins specifically expressed during yeast and
      pseudohyphal phases. Image analysis resolved 3 spots that were specific to the
      pseudohyphal phase and 2 spots that were specific to yeast phase. In addition to
      phase-specific proteins, important regulation of protein expression took place. A
      group of 9 proteins was highly over-expressed during the yeast phase when another
      group of 12 was underexpressed. This phenomenon was reversed during the
      pseudohyphal phase. These experiments showed that dimorphism in S. cerevisiae is
      associated with the expression of specific proteins and suggest that yeast phase
      specific proteins maintain the yeast form or repress pseudohyphae formation.

PMID- 9144563
TI  - Chromosomal localization of the human arginase II gene and tissue distribution of
      its mRNA.
AB  - Liver-type arginase (arginase I) is expressed almost exclusively in the liver and
      catalyzes the last step of urea synthesis, whereas the nonhepatic type (arginase
      II) is expressed in extrahepatic tissues and is probably involved in down
      regulation of nitric oxide synthesis. We isolated cDNA for human arginase II (T.
      Gotoh et al., 1996, FEBS Lett. 395, 119-122). Fluorescence in situ hybridization
      mapping and PCR mapping studies with somatic cell hybrid panels and a radiation
      hybrid panel localized the arginase II gene to chromosome 14q24.1-24.3. Dot-blot
      analysis showed that arginase II mRNA is expressed strongly in the adult human
      kidney and weakly in the prostate, pituitary gland, lung, liver, thyroid gland,
      and small intestine. The mRNA was either at very low levels or not detectable in
      the fetal kidney, lung, and liver. Thus, expression of the human arginase II gene
      is regulated both tissue-specifically and developmentally.

PMID- 9144564
TI  - Nitric oxide-releasing particles inhibit phagocytosis in human neutrophils.
AB  - We have constructed a yeast (Saccharomyces cerevisiae) particle capable of
      releasing NO, by loading heat-killed yeast particles with a hydrophobic NO
      generating substance, GEA-5171. This particle decreased phagocytosis in solution,
      as measured with flow cytometry, to about 80% of control values. Phagocytosis on
      a surface, as counted under the microscope, was also decreased by about 20%. The
      nitric oxide furthermore counteracted the production of oxygen metabolites by
      neutrophils to about 20% of control values. The inhibitory effect was most
      pronounced for the intracellular production, as could be seen when neutrophils
      preincubated with NO-releasing particles were stimulated with chemotactic agent
      (FMLP) or phorbol ester (PMA). In conclusion, NO has inhibitory effects on both
      phagocytosis and the respiratory burst of neutrophils. Since nitric oxide is a
      hydrophobic gas and an air pollutant, there is a possibility that it accumulates
      in particles which then become more resistant to elimination.

PMID- 9144565
TI  - Expression of prostaglandin endoperoxide H synthase 1 and 2 in human placenta at
      term.
AB  - Prostaglandins play an important role in reproduction, particularly in pregnancy
      and parturition. We investigated the expression of prostaglandin endoperoxide H
      synthase (PGHS) 1 and 2, key enzymes in prostaglandin biosynthesis, in the human
      placenta at term. Northern blot analysis of placenta total and poly(A)+ RNA
      failed to detect significant levels of PGHS-1 mRNA, using a human PGHS-1 specific
      DNA probe. In contrast, definite PGHS-2 mRNA bands, with a calculated size of
      about 4.5 kb, were observed in Northern blots of placenta poly(A)+ RNA, using a
      PGHS-2 specific DNA probe. Moreover, PGHS-1 and PGHS-2 expression was assessed at
      the translational level by Western blot analysis. Thus, using three highly
      specific antibodies, we found a selective expression of PGHS-2 immunoreactive
      protein. These results indicate that PGHS-2 is the PGHS isoform prevalently
      expressed in the human placenta at term and support the hypothesis that PGHS-2
      plays a prominent role in the maintenance of pregnancy, in line with the proposed
      anti-apoptotic and growth promoting properties of this enzyme.

PMID- 9144566
TI  - Reductase gene sequences and protein structures: p-cymene methyl hydroxylase.
AB  - Oxygenases are critical to cycling carbon in the biosphere and dependent on
      reductase action, principally from flavoprotein enzymes. Oxygenase diversity
      among organisms and strains carries a common theme of protein sequence and
      folding. p-Cymene (para-isopropyl toluene) was chosen as a point of convergence
      in terpene-aromatic mineralization to characterize a methyl hydroxylase electron
      transport system with the aerobe Pseudomonas aureofaciens. The cymA hydroxylase
      reductase gene was isolated and sequenced and the protein primary structure
      deduced. Optimized amino acid sequence alignments of flavoprotein reductases
      revealed major similarities over protein length, in the binding domains for
      NAD(P)H, and the flavine centers of pro- and eukaryote systems.

PMID- 9144567
TI  - Protein synthesis inhibitors cycloheximide and anisomycin induce interleukin-6
      gene expression and activate transcription factor NF-kappaB.
AB  - In two human cell lines, MDA-MB-231 and HeLa, the inducible expression of the
      interleukin-6 (IL-6) gene by two protein synthesis inhibitors, cycloheximide and
      anisomycin, was compared with the induction by the most potent physiological
      inducer of IL-6 described to date, interleukin-1beta (IL-1beta). In cycloheximide
      or anisomycin treated cells, the accumulation of the IL-6 message and the
      activation of transcription factors required for IL-6 gene expression occurs at
      an extent similar to that obtained with IL-1beta. Furthermore, IL-6 mRNA
      accumulation stimulated by cycloheximide or anisomycin is almost completely
      inhibited in the presence of actinomycin D, indicating that this effect occurs
      mainly through the activation of the transcriptional machinery. These data
      indicate that transcriptional induction of the IL-6 gene by inhibitors of protein
      synthesis is triggered by the same nuclear signals as other inducers.

PMID- 9144568
TI  - A novel Mn++-dependent ribonuclease that functions in U16 SnoRNA processing in X.
      laevis.
AB  - The intron-encoded U16 small nucleolar RNA (snoRNA) is a component of a new
      family of molecules which originate by processing of pre-mRNA in which they are
      contained. The mechanism of U16 snoRNA biosynthesis involves an initial step of
      endonucleolytic cleavage of the pre-mRNA with the release of a pre-snoRNA
      molecule; the subsequent step consists of exonucleolytic trimming that produces
      mature U16 molecules. In order to identify the molecular components involved in
      this peculiar biosynthetic pathway, we have undertaken the characterization of
      the endonucleolytic activity by biochemical fractionation of Xenopus laevis
      oocyte nuclear extract. In this paper we show the production of a protein
      fraction (BSF) which is highly enriched for a specific endonucleolytic activity
      that exactly reproduces the cleavage pattern of the U16-containing pre-mRNA
      identified in vivo in X. laevis oocytes and in unfractionated nuclear extract.

PMID- 9144569
TI  - Apoptosis in the absence of poly-(ADP-ribose) polymerase.
AB  - Cleavage of poly-(ADP-ribose) polymerase is a process occurring early during the
      execution phase of apoptosis. Although in many experimental systems PARP cleavage
      indicates a point of no return, the significance of this proteolytic step for
      apoptosis remains unclear. Here we compare the susceptibility of cells from wild
      type mice and PARP-/- mice to several inducers of apoptosis. Neither the
      susceptibility of hepatocytes towards CD95 or TNF-mediated apoptosis nor the
      activation of PARP-cleaving caspases was modified in PARP-/- liver cells.
      Thymocytes with either genotype exhibited similar sensitivity to treatments with
      ceramide, dexamethasone, or etoposide. The sensitivity of primary neurons towards
      apoptosis induced by staurosporine, colchicine, potassium withdrawal,
      peroxynitrite, or the neurotoxin MPP+ was also unaltered. These data suggest that
      neither activation nor cleavage of PARP has a causal role in apoptotic cell death
      of primary, non-transformed cells.

PMID- 9144570
TI  - Expression of human inducible nitric oxide synthase is regulated by both promoter
      and 3'-regions.
AB  - One of the mechanisms underlying the induction of human inducible nitric oxide
      synthase (hiNOS) by cytokines is transcriptional regulation. However, previous
      reports suggest that in human cells, the cytokine activation of the hiNOS
      expression is accompanied by a drastic increase in cellular mRNA and protein
      content, but by little increment in transcriptional activity. We designed
      luciferase reporter constructs containing the hiNOS 5'-flanking region and 3'
      untranslated region (UTR). The construct containing both 5'-flanking region and
      3'-UTR plus its downstream canceled the constitutive activity of the reporter
      gene, and was more responsive to the cytokines. This is an initial attempt to
      highlight the important role played by the 3'-region of the hiNOS gene. Our
      studies provide the evidence that the cooperative interaction between the 5'
      promoter and the 3'-region conveys marked induction of the gene in the presence
      of cytokines.

PMID- 9144572
TI  - Cooperativity-induced optical anisotropy changes during the photocycle of
      bacteriorhodopsin.
AB  - Previous photoselection measurements showed that if the excitation is weak no
      optical anisotropy changes appear in immobilized purple membranes during the
      photocycle. The present study demonstrates that surprisingly at stronger
      excitations the anisotropy changes versus time. At 412 nm the dichroic ratio
      decreases after a few milliseconds, while at 570 nm the similar decrease is
      followed by an increase. The phenomenon cannot be described by tiltings of the
      retinal chromophore. It is the consequence of the cooperative interaction among
      the photocycling bacteriorhodopsin molecules that regulates the yields of more
      than one (expectedly two main) parallel pathways existing in the millisecond time
      domain of the photocycle.

PMID- 9144571
TI  - Intramuscular injection of expression plasmid DNA is an effective means of long
      term systemic delivery of interleukin-5.
AB  - It has been demonstrated that intramuscularly injected expression plasmid DNA is
      taken up by myofibers and subsequently expresses exogenous genes. In the present
      study, we assessed intramuscular DNA injection as a means of systemically
      delivering interleukin-5 (IL-5). We constructed an IL-5 expression plasmid,
      pCAGGS-IL-5, containing murine IL-5 cDNA under the control of the CAG promoter.
      The soleus muscle of mice was pretreated with bupivacaine. Two days later, mice
      were injected with pCAGGS-IL-5 or a control pCAGGS plasmid DNA at the same site.
      At 2 weeks after DNA injection, eosinophils had increased from 2-3% to 8-29% of
      peripheral white blood cells in 9 of 10 mice injected with pCAGGS-IL-5, while
      eosinophils never exceeded 3% in control mice injected with pCAGGS. IL-5 mRNA was
      present in the muscle area injected with pCAGGS-IL-5. IL-5 was also detectable by
      ELISA in the sera of most mice injected with pCAGGS-IL-5, but in none of the
      control mice. These results demonstrate that intramuscular plasmid injection
      serves as a useful method of systemically delivering cytokines by combining the
      strong CAG promoter and bupivacaine pretreatment.

PMID- 9144573
TI  - Identification and cDNA cloning of a novel mammalian C2 domain-containing
      phosphoinositide 3-kinase, HsC2-PI3K.
AB  - Phosphoinositide (PI) 3-kinases have been shown to have critical roles in signal
      transduction, cell transformation and intracellular protein trafficking. Reverse
      transcription polymerase chain reaction methods, using degenerate primers derived
      from the lipid kinase consensus region, were utilised to identify PI 3-kinases in
      the normal human breast. Here we report the cDNA cloning of a novel human PI 3
      kinase isoform, HsC2-PI3K. This PI 3-kinase is most closely related to the
      recently described C2 domain-containing family of PI 3-kinases which includes
      Drosophila PI3K_68D/cpk and murine cpk-m/p170. Sequence analysis suggests that
      HsC2-PI3K is a second distinct mammalian member of the C2 domain-containing PI 3
      kinase family. Northern blot analysis of human tissues indicates that HsC2-PI3K
      is widely expressed. Fluorescence in situ hybridisation has mapped HsC2-PI3K to
      chromosome 1q32.

PMID- 9144574
TI  - Sensitivity of human hepatocytes in culture to reactive nitrogen intermediates.
AB  - The cytotoxic effects of 3-morpholinosydnonimine (Sin-1) and S-nitroso-N
      acetylpenicillamine-amine (SNAP) on replicatively active human hepatocyte cells
      in culture was determined as a function of oxidant type. Both Sin-1 which yields
      nitric oxide and peroxynitrite following the generation of superoxide anion plus
      nitric oxide, and SNAP which generates nitric oxide, induced dose dependent
      decreases in the colony forming capabilities of the human hepatocytes. Sin-1 was
      much more cytotoxic (LD50 = 400 microM) than SNAP (LD50 = 1250 microM).
      Comparatively, both compounds were much less cytotoxic than H2O2 (LD50 = 96
      microM). Sin-1 induced 4-fold higher levels of cellular nitrite than that
      generated by the chemical in cell free medium. Nitrotyrosine, a marker of
      peroxynitrite formation in cells, was immunohistochemically detected in
      hepatocytes treated with both Sin-1 and SNAP. The formation of 3-nitrotyrosine by
      hepatocytes incubated with SNAP, suggests that hepatocytes generate intracellular
      superoxide which reacts with the exogenous nitric oxide derived from SNAP to
      produce intracellular peroxynitrite, resulting in the SNAP cytotoxicity. The
      enhanced levels of Sin-1 cytotoxicity on the hepatocytes is suggested to be due
      both to the chemical generation of peroxynitrite and superoxide anion by Sin-1.
      These data indicate that peroxynitrite is formed in cultured human hepatocytes
      inhibiting their replication, and that peroxynitirite may play a significant role
      in the pathogenesis of liver disease.

PMID- 9144575
TI  - Selective expression of HSP70-1 gene in the adrenal cortex but not in the medulla
      of thermally stressed rats.
AB  - The heat shock protein 70 (HSP70) gene expression in rat adrenal glands was
      investigated. In situ hybridization and Northern blotting revealed a marked
      increase of inducible HSP70 (HSP70-1) gene expression in the adrenal cortex, but
      not in the medulla, after whole body hyperthermia. In vivo footprinting assay of
      HSP70-1 promoter region suggested a possible involvement of other factor(s) in
      addition to the heat shock factor (HSF). We also detected significant increases
      of both ACTH and corticosterone in the plasma of the hyperthermic rats. These
      results suggested some physiological factors other than HSF may also participate
      in the tissue-specific induction of HSP70-1 gene in vivo.

PMID- 9144576
TI  - Detergent effects on the light-harvesting chlorophyll A/B-protein complex
      crystallization revealed by fluorescence depolarization.
AB  - Detergent effects on the pre-crystallization of light-harvesting chlorophyll a/b
      protein complex (LHCII) were investigated through the fluorescence depolarization
      method. Stable LHCII crystals were formed in the media containing Triton X-100
      (TX) or n-nonyl-beta-D-glucopyranoside (NG) and the crystallization efficients
      were dependent on their concentrations. The second virial coefficient of
      crystallizing system, estimated by the fluorescence depolarization analysis of
      LHCII, showed the most harmonious value under the condition yielding the most
      efficient crystallization of LHCII to suggest that some specific molecular
      interaction leading to the crystal growth would be induced according to the
      concentration of TX or NG.

PMID- 9144577
TI  - A novel endothelin receptor type-B-like gene enriched in the brain.
AB  - We report here our effort of cloning and characterization of a novel human gene,
      which encodes a putative human endothelin receptor type B like protein (hET(B)R
      LP), from a human hippocampus tissue cDNA library. hET(B)R-LP consists of 614
      amino acids with seven putative transmembrane domains. The deduced amino acid
      sequence of hET(B)R-LP is 52% similar and 26.7% identical to human endothelin
      type B receptor. A 4.0 kb mRNA of hET(B)R-LP is abundantly expressed in the human
      brain. The results of in situ hybridization and reverse transcriptase in situ
      gene amplification reveal tissue distribution and cellular localization of
      signals of hET(B)R-LP mRNA in the neuronal cells, particularly concentrated in
      Purkinje cells of the cerebellum, and neuronal cells of the hippocampus of human
      brain, including pyramidal cells of Ammon's horn and granule cells of the dentate
      gyrus. A 4.0 kb mRNA of hET(B)R-LP is also less abundantly expressed in the liver
      and the placenta. Expression of recombinant protein, hET(B)R-LP/HA, in cells of
      COS7 and HEK293 transfected with plasmid DNA, hET(B)R-LP/HA/pcDNA1/Amp, was
      confirmed by Northern blot analysis and by immunofluorescence staining of cells
      with anti-HA antibody. Specific binding of radiolabeled ET-1 and ET-3 to membrane
      preparations and to intact cells expressing recombinant protein of hET(B)R-LP/HA
      did not show any significant difference of binding properties between cells
      transfected with plasmid DNA, hET(B)R-LP/HA/pcDNA1/Amp, and cells untransfected,
      including both COS7 cells and HEK293 cells. The results of assays of measuring
      Ca++ mobilization and cAMP production in HEK293 cells indicate that ET-1, ET-3,
      bombesin and neuropeptide Y are unable to produce any kind of significant
      difference of Ca++ mobilization and cAMP production between HEK293 cells
      expressing recombinant protein and HEK293 cells untransfected or HEK293 cells
      transfected with vector DNA only (pcDNA1/Amp) in functional assays performed.
      Therefore, its ligand and physiological significance of hET(B)R-LP remains to be
      discovered.

PMID- 9144578
TI  - Ribulose-1,5-bisphosphate carboxylase/oxygenase from thermophilic red algae with
      a strong specificity for CO2 fixation.
AB  - Strongly carboxylase-specific ribulose-1,5-bisphosphate carboxylase/oxygenase
      (RuBisCO) was found in Galdieria partita and Cyanidium caldarium
      (Cyanidiophyceae). The relative specificity, VcKo/VoKc, of Galdieria and
      Cyanidium RuBisCO was 238 and 222, respectively; 2.4 to 2.5-fold that of higher
      plant RuBisCOs. The apparent Km of RuBisCO from the thermophilic red algae for
      CO2 was 6 to 7 microM and the smallest of the values reported so far for other
      RuBisCOs. The pre-rhodophyte Porphiridium purpureum, which lives at moderate
      temperatures, had RuBisCO with the relative specificity value of 144. A large
      difference (5.2 kcal x mol(-1)) in the activation energies between the
      carboxylase and oxygenase activities in Galdieria RuBisCO was a cause of the
      strong specificity for the carboxylase activity.

PMID- 9144579
TI  - Expression of sodium-dependent purine nucleoside carrier (SPNT) mRNA correlates
      with nucleoside transport activity in rat liver.
AB  - The expression of sodium-dependent purine nucleoside transport (SPNT) mRNA has
      been studied in physiological situations in which Na+-dependent nucleoside uptake
      in plasma membrane vesicles from rat liver was induced. Sodium-dependent uridine
      transport rates were induced in genetically obese Zucker rats, during liver
      regeneration after partial hepatectomy, and under euglycemic-hyperinsulinemic
      clamp. A PCR-generated fragment, based on a published SPNT sequence cloned from
      rat liver, was used as a probe in Northern blot analysis. We show that the
      hepatic mRNA levels of the putative sodium-dependent transport system SPNT
      correlate with the sodium-dependent uridine transport rates in plasma membrane
      vesicles from rat liver. These results suggest that the induction of the sodium
      dependent nucleoside transport expressed in liver parenchymal cells involves
      regulation of SPNT gene expression.

PMID- 9144580
TI  - Differential expression of tenascin-C and tenascin-X in human astrocytomas.
AB  - Tenascins (TNs) are a family of extracellular matrix glycoproteins. The first
      member of this family to be recognized, tenascin-C (TN-C), is known to be
      expressed in various tumors including human astrocytomas. Tenascin-X (TN-X) is
      the latest member of the TN family to be reported, and its expression in tumor
      tissues has not yet been examined. In this study, we found expression of TN-X in
      glioma cell lines and human astrocytomas by immunoblot analysis using anti-mouse
      TN-X antibodies. We also examined the expression of TN-C and TN-X
      immunohistochemically in a series of 32 human astrocytomas and tissue from 5
      normal brains. Expression of TN-X was up-regulated to a higher degree in low
      grade astrocytomas than in high-grade astrocytomas. TN-X was mainly localized in
      the perivascular stroma around tumor vessels, and weakly expressed in the
      intercellular spaces among tumor cells. In contrast, TN-C was more strongly
      expressed in the intercellular spaces and in tumor vessels in high-grade
      astrocytomas (anaplastic astrocytomas and glioblastomas) than in low-grade
      astrocytomas. In the tissues expressing both TNs, the distribution of TN-X was
      often reciprocal to that of TN-C. These findings indicate that the expression of
      TN-C and TN-X in astrocytomas is different, and that these glycoproteins could be
      involved in neovascularization in different manners.

PMID- 9144581
TI  - Altered expression of src tyrosine kinase after axotomy.
AB  - Although most peripheral neurons show regenerative changes after axotomy, neurons
      of some nuclei show degenerative changes. To study the mechanisms responsible for
      such differences in neuronal reactions after axotomy, we investigated the changes
      of pp60c-src and phosphotyrosine (pTyr) in the dorsal motor nucleus of the vagus
      nerve and the hypoglossal nucleus after transection of each nerve in adult rats
      using immunohistochemistry. Polyclonal antibody against pp60v-src stained the
      cytoplasm of neurons homogeneously in both the severed and non-severed sides of
      the vagal and hypoglossal nuclei from days 1 to 56 after axotomy. On the other
      hand, the monoclonal antibody against pp60v-src (mAb327, which recognizes src
      homology 3 region in pp60src as an epitope) showed different immunoreactivities.
      No pp60c-src immunoreactivity was observed in neurons in either the vagal and
      hypoglossal nuclei of the non-severed side between days 1 and 56, whereas in the
      severed side of the hypoglossal nucleus intense pp60c-src immunoreactivity was
      observed along the plasma membrane of neurons from days 5 to 28 after axotomy. In
      contrast, in the severed side of the vagal nucleus pp60c-src immunoreactivity
      appeared along the plasma membrane of neurons on day 5 and remained until day 7.
      Conformational changes accompanying the activation of pp60c-src are suggested to
      cause differences in immunoreactivities of these antibodies. The expression (or
      activation) of pp60c-src in the neurons was stronger and longer lasting in the
      hypoglossal nucleus, which regenerates successfully after axotomy, than in the
      dorsal motor nucleus of the vagus nerve, which undergoes necrobiotic reaction.
      These results indicate that pp60c-src plays an important role in regeneration
      after axotomy.

PMID- 9144582
TI  - Short- and long-term effects of low-dose prenatal X-irradiation in mouse cerebral
      cortex, with special reference to neuronal migration.
AB  - To elucidate the short- and long-term effects of ionizing radiation on cell
      migration in the developing cerebral cortex, we labeled proliferating cells on
      day 14 of gestation of mice with bromodeoxyuridine (BrdU) followed by a single
      exposure to 0.1-1 Gy of X-rays. The brains of embryos on day 17 and offspring at
      2, 3 and 8 weeks after birth were processed for BrdU immunohistochemistry to
      trace the movements of BrdU-labeled cells. The location of BrdU-labeled neurons
      in the cerebral cortex was quantitatively analyzed between irradiated animals and
      non-irradiated controls. We have demonstrated that the initial migration of BrdU
      labeled cells from the matrix cell zone towards the cortical plate during
      embryonic periods was decelerated when exposed to X-rays of 0.25, 0.5 and 1 Gy on
      embryonic day 14, and that aberrantly placed neurons in the cerebral neocortex
      were noted in younger animals that were irradiated prenatally, whereas such
      derangement was less pronounced in mature animals. These observations suggest
      that some modification process might have occurred during the postnatal period.

PMID- 9144583
TI  - Development of cerebellar hypoplasia in jaundiced Gunn rats: a quantitative light
      microscopic analysis.
AB  - The homozygous (ii) Gunn rat provides a model for hyperbilirubinemia which
      includes prominent cerebellar hypoplasia. Development of the Gunn rat cerebellum
      was examined with and without the additional effects of elevating brain bilirubin
      concentration to still higher levels via sulfadimethoxine (sulfa) administration.
      Homozygous (jj) Gunn rats and heterozygous (Nj) littermate controls (n = 32 each)
      were given 100 mg/kg sulfa or saline at postnatal days 3, 7, 17, and 30, and most
      were sacrificed 24 h later (n = 4 for each genotype at each age). Cerebellar
      volume, total volume and cell number for each deep cerebellar nucleus, densities
      for Purkinje and granule cells in the cerebellar cortex of lobules II, VI and IX,
      and the density of vacuolated Purkinje cells were all measured quantitatively.
      Cytoplasmic vacuolation provided an indication of bilirubin toxicity and was
      never observed in the Nj control rats. Vacuolated Purkinje cells were first
      observed in jj-saline rats at 18 days and were found only in the more anterior
      lobules of the cerebellum (II and VI). By contrast, vacuolated Purkinje cells
      were observed in jj-sulfa rats at both 4 and 8 days, but only in the most
      posterior cerebellar lobule (IX). In all older jj rats, the decline in
      vacuolation was accompanied by significant necrosis and resorption of the
      Purkinje cells in the anterior lobules. Since the Purkinje cells in the posterior
      lobules are the first to differentiate in the cerebellum and are resistant to
      bilirubin toxicity in jj-saline rats, the results support the presence of a
      critical period when elevated brain bilirubin may be most toxic to neuronal
      development. The findings suggest that neurons undergoing differentiation at the
      time of bilirubin exposure are most susceptible to cell death, while cells that
      are slightly more or slightly less mature may show only transient changes.

PMID- 9144584
TI  - Establishment and characterization of cell lines derived from a transplantable
      rat malignant meningioma: morphological heterogeneity and production of nerve
      growth factor.
AB  - A cell line (KMY-J) was established from a transplantable tumor (MM-KMY) derived
      from a spontaneous malignant meningioma arising in an aged F344 rat, and three
      cloned cell lines (KMY-1, KMY-2 and KMY-3) were induced from the parent KMY-J.
      Morphologically, KMY-J and tumors induced in syngeneic rats by KMY-J showed cell
      pleomorphism. All neoplastic cells in KMY-J and its tumors were immunoreactive to
      vimentin; occasional cells reacted to ED1 (rat macrophage/histiocyte-specific
      antibody) and alpha-smooth muscle actin (alpha-SMA), indicating expression of
      histiocytic or myofibroblastic immunophenotypes of meningioma cells. In contrast,
      KMY-1, KMY-2 and KMY-3 consisted of a uniform cell population differing from each
      other. KMY-1-induced tumors were similar histologically to meningeal
      fibrosarcomas. Dendritic cells seen in KMY-2 cultures gave an appearance of
      arachnoid trabecular cells. In KMY-3 and its tumors, large round cells and
      multinucleated giant cells were predominant. Cells of these cloned cell lines
      also reacted to vimentin, but were negative for ED1 and alpha-SMA. By the
      bioassay using PC12 cells and reverse transcription-polymerase chain reaction for
      nerve growth factor (NGF) mRNA, production of NGF was demonstrated in the parent
      and cloned cell lines. The present cell lines may prove useful for studying the
      histological features of meningeal tumors and the bioactive factors produced by
      meningeal cells.

PMID- 9144585
TI  - Carbohydrate antigen 19-9 expression by folliculo-tubular structures of normal
      and neoplastic pituitary.
AB  - We demonstrated immunohistochemically that follicular lining cells of anterior
      pituitary display carbohydrate antigen 19-9 (CA19-9) at their luminal surfaces.
      CA 19-9 was also demonstrated in the tubular structures of the intermediate lobe.
      Until now this antigen of exocrine ducts, such as pancreatic and salivary ducts,
      has not been demonstrated in endocrine tissue. Some CA19-9 positive follicular
      cells also showed endocrine markers such as chromogranin, synaptophysin and
      pituitary hormones. In pituitary adenomas, frequently-seen follicular structures
      showed immunohistochemical features similar to non-neoplastic follicles.
      Expression of CA19-9 in the adenohypophysis may be related to its origin from an
      anlage, the stomodeum shared with the parotid gland. The lining cells and mucin
      of Rathke's cleft cysts also revealed CA19-9. Accordingly, these cysts could have
      arisen from follicular cells with an exocrine ductal phenotype. The transitional
      cell tumor of Kepes also showed CA19-9 at the luminal surfaces of cells and in
      the mucin of large cysts. Given that smaller mucin-laden cysts appeared fairly
      frequently in adenomas, the transitional cell tumor may be a kind of pituitary
      adenoma with follicles in which many cells produce excessive mucin.

PMID- 9144586
TI  - Argyrophilic grain disease: widespread hyperphosphorylation of tau protein in
      limbic neurons.
AB  - Argyrophilic grains (ArG) and coiled bodies of argyrophilic grain disease (AgD)
      and the neurofibrillary lesions of Alzheimer's disease (AD) share similar
      antigenic determinants, among them hyperphosphorylated microtubule-associated
      protein tau. Nothing is known about the mechanisms underlying tau
      hyperphosphorylation in AgD, the hyperphosphorylated sites or the intracellular
      distribution of abnormally phosphorylated tau. We have analysed brain tissue
      sections from 41 subjects with AgD with a panel of phosphorylation-dependent
      (AT270, AT8, Tau-1, AT180, 12E8, PHF-1 and AT100) and phosphorylation-independent
      anti-tau antibodies (N-tau 5, 304, 189 and 134). All antibodies labelled ArG,
      coiled bodies and neurofibrillary lesions, with the exception of antibody 12E8,
      which stained a subset of neurofibrillary tangles, but no ArG or coiled bodies.
      Most pyramidal neurons in areas rich in ArG showed diffuse granular tau labelling
      in cell bodies and dendrites. Only very few tau-positive cells also contained
      neurofibrillary tangles. Phosphorylation-dependent anti-tau antibodies also
      stained a felt-like network of Gallyas-negative filiform neurites in layer CA1 of
      the hippocampus and in layer pre-B of the transentorhinal cortex. These results
      demonstrate a widespread hyperphosphorylation of tau protein in the
      somatodendritic domain of neurons in AgD, in addition to silver grains in the
      neuropil. Unlike in AD, tau hyperphosphorylation in the somatodendritic domain in
      AgD does not appear to be followed by neurofibrillary tangle formation, even in
      the presence of widespread ArG in the neuropil. Furthermore, our data suggest
      that no strict correlation exists between the presence or density of ArG in the
      limbic area and the occurrence of dementia.

PMID- 9144587
TI  - Neuropathology of normothermic circulatory arrest in newborn dogs.
AB  - Neuropathologic findings are described, for the first time, in a neonatal dog
      model of circulatory arrest in normothermic conditions, and the findings are
      compared to those reported in neonatal dogs with hypothermic circulatory arrest.
      Total circulatory arrest was produced in 3- to 6-day-old anesthetized, paralyzed
      and ventilated, normothermic dogs either by asphyxiation or cardioplegia.
      Duration of circulatory arrest was 8-20 min and 10-40 min in asphyxiated and
      cardioplegic animals, respectively. The animals were resuscitated and maintained
      under controlled systemic physiologic conditions until neuropathologic
      examination after 8 or 24 h of recovery. The results suggest that the minimal
      durations of circulatory arrest for brain damage to occur following asphyxia or
      cardioplegia are 10 and 15 min, respectively. Ischemic lesions in both groups
      consisted of neuronal necrosis and involved mainly the brain stem structures,
      particularly the reticular nuclei and the spinal cord gray matter. The medulla
      was more severely involved than midbrain and pons. There was a direct correlation
      between the length of circulatory arrest and the severity of damage in the
      medulla (P = 0.001) and overall brain stem damage (P = 0.004) in animals with
      cardioplegia, but not in animals with asphyxia. These findings are compared to
      the neuropathologic changes previously described in newborn dogs subjected to
      hypothermic circulatory arrest, in which ischemic lesions are focused on the
      cerebral cortex and basal ganglia. It is concluded that hypothermia in this model
      not only prolongs the period of circulatory arrest that is required to produce
      brain damage, but also shifts the pattern of regional ischemic vulnerability from
      caudal to more rostral structures.

PMID- 9144588
TI  - Cystatin C and transthyretin expression in normal and neoplastic tissues of the
      human brain and pituitary.
AB  - The localization of cystatin C (CC) and transthyretin (TTR) synthesis was studied
      using Northern blot and immunohistochemical methods. Normal brain tissues from
      all sites studied contained CC mRNA. Immunoreactive CC was present in the choroid
      plexus epithelial cells, cerebral and cerebellar neurons, astrocytes, ependymal
      cells, macrophage-like cells of the arachnoid membrane and in neuroendocrine
      cells of the anterior pituitary lobe. TTR mRNA and TTR were restricted to the
      choroid plexus. In primary brain tumors, the transcript for CC was found in all
      39 tumors examined, while the protein could only be demonstrated in 3/5 choroid
      plexus papillomas, 8/8 astrocytomas, 7/23 anaplastic astrocytomas and
      glioblastomas, 1/6 oligodendrogliomas, 1/1 oligoastrocytoma, 1/4 anaplastic
      oligodendrogliomas, 3/7 ependymomas, 0/1 anaplastic ependymoma, 0/5 primitive
      neuroectodermal tumors, 0/1 neuroblastoma, 3/11 meningiomas and 16/16 pituitary
      adenomas. CC cannot be used as a marker for any specific brain tumor type but the
      fact that the protein could be demonstrated more frequently in astrocytomas than
      in their more malignant counterparts suggests that the cellular production and
      secretion of CC changes with the malignant progression of these tumors. TTR mRNA
      and TTR were present only in the choroid plexus papillomas, indicating that TTR
      synthesis is mainly restricted to such brain neoplasms.

PMID- 9144589
TI  - Dissociation of Alzheimer type pathology in a disconnected piece of cortex.
AB  - A woman with Alzheimer's disease died at the age of 85 years. A left sphenoid
      meningioma had been removed 27 years earlier. The tumor and the operation had
      severely altered the white matter of the frontal lobe and of the anterior part of
      the temporal lobe on the left side and massively disconnected a small piece of
      frontal cortex. There were numerous senile plaques and neurofibrillary tangles in
      the limbic and isocortical samples. The white matter lesions, on the operated
      (left) side, were associated with a lower density of neuritic plaques and of
      neuropil threads and with a higher density of beta-amyloid (A beta) deposits. The
      density of tau-positive neuritic plaques, neurofibrillary tangles and neuropil
      threads was close to zero, whereas the diffuse deposits of A beta were abundant,
      in the small disconnected piece of cortex. In this area, the white matter was
      severely damaged, as in the adjoining cortex, but the continuity of the cortical
      ribbon was also disrupted. These data show that neuritic and A beta pathologies
      may be dissociated and suggest that the neuritic alterations mainly involved
      cortico-cortical fibers coursing tangentially in the cortical ribbon.

PMID- 9144590
TI  - Tumor necrosis factor-alpha, microglia and astrocytes in AIDS dementia complex.
AB  - The pathogenesis of HIV-associated cognitive changes is poorly understood.
      Cytokines such as tumor necrosis factor-alpha (TNF-alpha) have been postulated to
      contribute to the mechanism of the neurological complications of HIV infection.
      One of the effects of TNF-alpha is to induce astrocyte proliferation in vitro.
      The purpose of this study was to look for a correlation between the expression of
      TNF-alpha, astrogliosis and the degree of cognitive impairment in 12
      prospectively assessed AIDS cases without focal brain lesion, 8 of whom were
      demented. They were compared with 6 control patients without neurological
      disease. Neuropathological examination showed myelin pallor in 5 of the 8
      demented patients. TNF-alpha expression was detected by immunohistochemistry in
      the midfrontal cortex, subcortical and deep white matter, and basal ganglia. Not
      only perivascular macrophages but also some microglial and endothelial cells were
      labeled. Most TNF-alpha-positive cells were in close contact with glial
      fibrillary acidic protein-positive astrocytes. They were more numerous than gp41
      positive cells. Their density increased with increasing cognitive impairment and
      in parallel to the astrogliosis in the frontal cortex, basal ganglia and deep
      white matter. These findings further support the hypotheses that lesions of the
      deep white matter, driven by TNF-alpha, are associated with cognitive alteration,
      and that indirect effects of HIV infection in the brain participate in the
      development of HIV-associated dementia through a diffuse immune activation,
      mediated by cytokines.

PMID- 9144591
TI  - Monocyte chemoattractant protein-1 expression and macrophage infiltration in
      gliomas.
AB  - While the number of reports on macrophage infiltration of gliomas is increasing,
      the extent and mechanisms of macrophage recruitment remain unclear. To
      investigate whether monocyte chemoattractant protein-1 (MCP-1) plays a role in
      this process, in situ hybridisation (ISH) was performed for 22 glioblastomas
      (GBM), 1 anaplastic astrocytoma (AA) and 4 grade II fibrillary astrocytomas (AII)
      and reverse transcription-polymerase chain reaction was performed in 13 GBM, 1 AA
      and 3 AII. High levels of MCP-1 mRNA were detectable in most GBM, while a lower
      level was detected in AII. Many tumour-associated macrophages (TAM) could be
      demonstrated by immunohistochemistry (IHC) in most GBM, while the AII contained a
      lower number of TAM. The positive correlation between the MCP-1 level and
      abundance of TAM suggested that MCP-1 has a role in TAM recruitment. By combining
      ISH and IHC, high levels of MCP-1 mRNA were shown both in tumour cells and TAM.
      Along tumour borders, reactive astrocytes and microglia also expressed MCP-1. In
      areas with T lymphocyte infiltration, larger numbers of MCP-1-positive cells with
      an enhanced level of expression could be identified. We propose that the
      mechanism of macrophage recruitment is, at least partly, effected by constitutive
      expression and T cell-mediated up-regulation of MCP-1 in tumour cells and TAM.
      The production of MCP-1 by TAM establishes a positive amplification circuit for
      macrophage recruitment in gliomas.

PMID- 9144592
TI  - Ubiquitin-immunoreactive granular inclusions in neuronal migration disorders.
AB  - This report describes novel ubiquitin-immunoreactive inclusions in neurons in 3
      out of 27 patients with neuronal migration disorders (NMDs). One patient was
      pathologically diagnosed as having cortical microdysgenesis, and the other two
      were consistent to have polymicrogyria. The inclusions were present in the
      perikaryon as compact granular structures, 0.5-2 microns in diameter. Since
      ubiquitin acts as a cellular scavenger and has a crucial role in selective
      protein degradation, the presence of ubiquitin-immunoreactive inclusions suggests
      that altered or abnormal proteins may accumulate in neurons in NMDs, although the
      nature of accumulated proteins remains unknown.

PMID- 9144593
TI  - Eosinophilic intranuclear inclusions in the hippocampal pyramidal neurons of a
      patient with amyotrophic lateral sclerosis.
AB  - We report the presence of round eosinophilic intranuclear inclusions in a patient
      with sporadic amyotrophic lateral sclerosis (ALS). The inclusions were limited to
      the hippocampal pyramidal neurons; they were frequently encountered in the CA1
      and CA2 regions and much less frequently in the CA3 and CA4 regions and in the
      subiculum. Ultrastructurally, they consisted of randomly oriented straight
      filaments, each about 8-14 nm in diameter, some of which had a tubular appearance
      in cross-section. Electron-dense, granular material was intermingled with the
      filaments. Immunohistochemically, all the inclusions were positive for ubiquitin,
      but were negative for several kinds of cytoskeletal protein, including actin,
      glial fibrillary acidic protein, vimentin, neurofilament polypeptides, keratin,
      tubulin, tau protein and microtubule-associated protein 2. To our knowledge, this
      type of neuronal intranuclear inclusion has not so far been reported in ALS, and
      its distribution limited to the hippocampal formation is of great interest.

PMID- 9144594
TI  - Operative management of the stiff elbow: sequential arthrolysis based on a
      transhumeral approach.
AB  - Between December 1990 and September 1993, 26 consecutive patients (27 elbows)
      were treated for elbow contractures. We used a modified transhumeral approach
      supplemented by a limited lateral approach with or without a limited medial
      approach according to the correction gained after each step of the procedure.
      Eleven posttraumatic, 6 degenerative, and 10 miscellaneous contractures were
      evaluated. The mean follow-up was 30 months. Statistically significant
      improvement in the range of motion was obtained for all groups of patients; the
      mean flexion-extension arc of motion increased from 66 degrees to 100 degrees for
      the posttraumatic contractures, from 79 degrees to 102 degrees for the
      degenerative contractures, and from 85 degrees to 121 degrees for a miscellaneous
      group of contractures. Relief of pain was not an issue in the posttraumatic
      group; it was not significant for the degenerative group but was significant for
      the miscellaneous group. Flexion and extension force were maintained, and no
      joint was made unstable. Complications included three transient ulnar
      neuropathies and one tardy ulnar nerve palsy. The technique presented offers the
      advantage of virtually unlimited exposure of the joint in a stepwise manner,
      dictated by the intraoperative assessment of joint motion combined with
      preservation of the medial and lateral collateral ligament complexes and all
      relevant muscle insertions and origins. The concept is applicable to contractures
      of differing cause and can be adapted to the specific needs of the patient.

PMID- 9144595
TI  - Anterior intramuscular transposition of the ulnar nerve for cubital tunnel
      syndrome.
AB  - Forty-five sequential cubital tunnel releases with anterior transposition of the
      ulnar nerve in an intramuscular fashion were performed over a 4-year period. All
      patients had a positive Tinel's sign at the cubital tunnel and reported numbness
      and tingling in the ring and small finger of the affected arm. Thirty-three cases
      had preoperative electrodiagnostic studies performed. Twenty-three cases had
      positive electromyographic and nerve conduction velocity findings for cubital
      tunnel syndrome, whereas 10 cases had normal electromyographic and nerve
      conduction velocity studies. Twenty-four cases were covered by Workers'
      Compensation insurance. The average age of the patients was 40 years, with an
      average duration of symptoms of 22 weeks. Average follow-up examination was 15
      months, with all patients being reexamined and completing a symptom outcome
      questionnaire. No significant differences between preoperative electrodiagnostic
      status could be demonstrated with regard to final symptom outcome. Patients with
      improved results from a symptom status were younger and had cubital tunnel
      syndrome of shorter duration. A trend toward poor results in patients with
      Workers' Compensation was noted, although this was not statistically significant.
      Overall, 87% of the patients had resolved or improved symptoms after cubital
      tunnel release with the anterior intramuscular transposition technique.

PMID- 9144596
TI  - Bone strength and material properties of the glenoid.
AB  - The quality of the glenoid bone is important to a successful total shoulder
      replacement. Finite element models have been used to model the response of the
      glenoid bone to an implanted prosthesis. Because very little is known about the
      bone strength and the material properties at the glenoid, these models were all
      based on assumptions that the material properties of the glenoid were similar to
      those of the tibial plateau. The osteopenetrometer was used to assess the
      topographic strength distribution at the glenoid. Strength at the proximal
      subchondral level of the glenoid averaged 66.9 MPa. Higher peak values were
      measured posteriorly, superiorly, and anteriorly to the area of maximum concavity
      of the glenoid joint surface known as the bare area. One millimeter underneath
      the subchondral plate, average strength decreased by 25%, and at the 2 mm level
      strength decreased by 70%. The contribution of the cortical bone to the total
      glenoid strength was assessed by compression tests of pristine and cancellous
      free glenoid specimens. Strength decreased by an average of 31% after the
      cancellous bone was removed. The material properties of the glenoid cancellous
      bone were determined by axial compression tests of bone specimens harvested from
      the central part of the glenoid subchondral area. The elastic modulus varied from
      approximately 100 MPa at the glenoid bare area to 400 MPa at the superior part of
      the glenoid. With the elastic constants used a predictor of the mechanical
      anisotropy, the average anisotropy ratio was 5.2, indicating strong anisotropy.
      The apparent density was an average 0.35 gr. cm-3, and the Poisson ratio averaged
      0.263. According to our findings the anisotropy of the glenoid cancellous bone,
      details concerning the strength distribution, and the load-bearing function of
      the cortical shell should be considered in future finite element models of the
      glenoid.

PMID- 9144597
TI  - Anthropometric study of normal glenohumeral relationships.
AB  - Ninety-three cadaveric proximal humeri and matching scapulae with no evidence of
      shoulder disease were obtained. High-resolution roentgenograms were made. They
      were the digitized, and a custom computer program was used to obtain periosteal
      and endosteal dimensions (humeral canal width, shaft width, tuberosity offset,
      head offset, radius of curvature, head diameter, canal flare index, glenoid
      height and depth, arc of enclosure, radius of curvature, and depth of cancellous
      bone, among others). Statistical analyses included correlations among pairs of
      dimensions, regression analysis, and confidence intervals to estimate each
      geometric parameter. To represent the degree of conformity and constraint between
      the humeral head and glenoid, a conformity index (radius of head/radius glenoid)
      and constraint index (arc of enclosure/360) were calculated for each shoulder.
      Most of the parameters measured approximated a Gaussian distribution. Pairwise
      correlations of the geometric parameters showed that many were significantly
      associated at the 5% level (p < 0.05) with a high correlation coefficient (r >
      0.4), meaning that the variations between the parameters were not purely random
      but rather they were related and that this relationship was useful in a
      predictive sense. With these key parameters identified, one can design components
      with an optimum fit or match an existing design to a patient's anatomy with a
      high degree of accuracy. No correlation was found between the radii of curvature
      for the humeral head and glenoid in either the coronal or sagittal plane or
      between the humeral head diameter and arc of enclosure. The mean conformity index
      was 0.72 in the coronal and 0.63 in the sagittal plane. Only 16% of the specimens
      had a conformity index greater than 0.9, indicating the radii of curvature
      matched. The vast majority had a more curved humeral head and flatter glenoid.
      Also, there was more constraint to the glenoid in the coronal versus sagittal
      plane (constraint index = 0.18 vs 0.13). These anatomic features help prevent
      superior-inferior translation of the humeral head but allow translation in the
      sagittal plane. This database of basic anatomic geometry defines the anatomic
      relationships of the proximal humerus and glenoid cavity that allow for a precise
      bone-implant fit and assesses the match between the shape of existing components
      and the patient's anatomy.

PMID- 9144598
TI  - Dissociation of modular humeral head components: a biomechanical and implant
      retrieval study.
AB  - In vivo dissociation of the Morse-taper of shoulder arthroplasty modular humeral
      components has been reported. The incidence of this complication appears to be
      approximately 1:1000. The objective of this study was to identify conditions that
      might affect the Morse-taper interface strength in humeral components. Mechanical
      tests were performed to load and dissociate humeral heads from the humeral stems
      (titanium). The effect of loading rate, load amplitude, and number of impactions
      was investigated. Dissociation force was measured after the taper was
      contaminated with water, oil, blood, and bone cement particles. The mean
      dissociation force after two impactions with a mallet was 2926 +/- 955 N.
      Dissociation force was linearly proportional to impaction force. Repetitive
      loading beyond two impactions did not significantly increase taper strength.
      Contamination of the taper with as little as 0.4 ml of fluid could prevent
      fixation of the taper.

PMID- 9144599
TI  - Shoulder function after surgical repair of rotator cuff tears.
AB  - Shoulder function was assessed in 37 patients with a mean age of 57 years after
      acromioplasty and repair of full-thickness rotator cuff tears were performed. The
      cuff tears were closed without transfer of other muscles or use of synthetic
      materials. At review 2 years after surgery 32 patients had significant pain
      relief and improved shoulder function. Range of motion, muscle strength, and
      endurance were increased. The mean Constant score was 77, and 80% of the patients
      were graded as having mild or disability. Radiographic measurements disclosed an
      increased supraspinatus outlet area after surgery. It is concluded that in
      patients with impingement syndrome and a full-thickness rotator cuff tear,
      shoulder function will be improved after acromioplasty and cuff repair, but a
      slight decrease in range of motion and muscle strength will remain when compared
      with the contralateral side.

PMID- 9144600
TI  - "Bursal reactions" in rotator cuff tearing, the impingement syndrome, and
      calcifying tendinitis.
AB  - Subacromial bursal specimens from 63 patients undergoing surgery for rotator cuff
      tearing (n = 43), the impingement syndrome (n = 14), and calcifying tendinitis n
      = 6) were studied to characterize the reactions that develop at the tendinopathy
      "lesional" sites. Intensity of the bursal reactions and production of type III
      collagen vary considerably, with the highest incidence of both seen in patients
      with rotator cuff tears. The intensity of bursal reactions correlated with the
      degree of formation of perivascular new collagen and type III collagen
      expression. In 22 of the 63 patients the bursal reaction distant to the tendon
      lesion was also studied. It was minimal and did not correlate to the lesional
      bursal findings. A strong correlation, however, existed between surgical
      appearance and histologic grading. The term "localized bursal reaction" as
      opposed to bursitis more correctly describes bursal involvement. Resection of
      bursal tissues should be limited to the lesional tissue that interferes with
      subacromial motion.

PMID- 9144601
TI  - Mechanical strength of latissimus dorsi tendon transfer with Teflon felt
      augmentation.
AB  - Tensile properties of Teflon felt augmentation after latissimus dorsi tendon
      transfer to rotator cuff defect were examined in dog cadaver shoulders. Two
      experimental groups with latissimus dorsi tendon transfer were designed. In group
      1 (right shoulders, n = 7) the tendon ends of latissimus dorsi were sutured to
      the greater tuberosity. In group 2 (left shoulders, n = 7) the repair was
      augmented with Teflon felt at the suture site. The ultimate tensile force and
      stiffness of each specimen in group 2 were individually compared with those in
      group 1. The average increases in ultimate tensile force and stiffness in group 2
      were 53.8% and -3.7%, respectively. The individual value of ultimate tensile
      force in group 2 was significantly greater than that in group 1. These results
      demonstrate that augmentation at the repair site is mechanically effective
      latissimus dorsi tendon transfer. The augmentation procedure may provide
      protection during the healing period because of this and a surrounding fibrous
      tissue reaction.

PMID- 9144602
TI  - The relation between the position of the glenohumeral joint and the
      intraarticular pressure: an experimental study.
AB  - Intraarticular pressures of the glenohumeral joint were measured in 15 cadaveric
      shoulders during passive movement of the humerus and under various inferiorly
      directed loads on the humerus. With a fiber-optic transducer-tipped catheter and
      an airtight connector, the basic intraarticular pressure was measured directly
      without injection of any physiological saline solution into the joint before
      measurement. The initial intraarticular pressures were all negative with a mean
      value of -67.8mm Hg. During abduction-adduction movement the minimal
      intraarticular pressure was measured at 20 degrees of humeral abduction. During
      rotation the minimal intraarticular pressure was observed at neutral humeral
      rotation. The intraarticular pressure decreased nearly linearly with increasing
      inferior load on the humerus. These results indicate that the intraarticular
      pressure takes part in stabilization of the glenohumeral joint, and the negative
      intraarticular pressure of the glenohumeral joint induces the maximal stabilizing
      effect at 20 degrees of humeral abduction and neutral humeral rotation.

PMID- 9144603
TI  - Reflex muscle contraction in anterior shoulder instability.
AB  - Reduced proprioception may contribute to recurrent anterior shoulder instability.
      Twelve patients with unilateral shoulder instability were investigated for
      evidence of deficient proprioception with an activated pneumatic cylinder and
      surface electromyography electrodes; the contralateral normal shoulder was used
      as a control. The latency between onset of movement and the detection of muscle
      contraction was used as an index of proprioception. No significant difference in
      muscle contraction latency was detected between the stable and unstable
      shoulders, suggesting that there was no significant defect in muscular reflex
      activity. This study does not support the use proprioception-enhancing
      physiotherapy in the treatment of posttraumatic anterior shoulder instability.

PMID- 9144604
TI  - Surgical arthrodesis of the sternomanubrial joint in a patient with psoriatic
      arthritis.

PMID- 9144606
TI  - Rapid development of subscapular exostosis bursata.

PMID- 9144605
TI  - Osteochondritis dissecans of the humeral head: treatment with a matched
      osteochondral allograft.

PMID- 9144607
TI  - Evaluating outcome after spinal cord injury: what determines success? 1996 Donald
      Munro Lecture.

PMID- 9144608
TI  - Management of pain in persons with spinal cord injury.
AB  - Pain is a common complaint following spinal cord injury (SCI). While nociceptive
      pain can often be effectively managed by traditional therapies, neurogenic pain
      is more refractory to treatment. Several categories of pain are recognized in
      persons with SCI and an accurate diagnosis will improve the therapeutic response.
      Nociceptive pain is usually perceived to be above or at the level of the cord
      lesion and is most commonly related to musculoskeletal pathology. Neurogenic pain
      is usually felt by the patient at or below the neurological level and may be
      classified as radicular, segmental or deafferentation central pain, depending on
      its hypothetical origin and the clinical presentation. Management requires
      recognition of all factors that may influence pain perception and knowledge of
      the entire range of therapeutic options.

PMID- 9144609
TI  - Axonal sprouting following incomplete spinal cord injury: an experimental model.
AB  - Recovery of function following incomplete spinal cord injury may in part result
      from growth of new connections by spared descending pathways. It has been
      difficult to demonstrate such anatomical reorganization with traditional anatomic
      techniques. This study utilizes an immunocytochemical method to demonstrate
      axonal growth cones within the lumbar spinal cord in rats recovering from an
      incomplete midthoracic spinal cord injury. Adult rats underwent subtotal section
      of the midthoracic cord sparing the left lateral funiculus and a portion of the
      left ventral funiculus. Light microscope immunocytochemistry was performed on
      sections of lumbar spinal cord with antibodies to identify sprouting axons. These
      antibodies were used to determine the distribution of growth cones on both sides
      of the lumbar spinal cord in experimental and control animals. Growth cones were
      first observed three days after the spinal cord lesion. Specific labeling,
      similar in appearance to previous reports of growth cone identification, was
      apparent within the immediate gray and ventral horns on both sides of the cord.
      These data support the hypothesis of collateral sprouting distal to the lesion
      site following incomplete spinal cord injury. It further supports the idea that
      recovery of function following incomplete spinal cord injury is, in part,
      mediated by spared descending pathways.

PMID- 9144610
TI  - Prognostic significance of the delayed plantar reflex following spinal cord
      injury.
AB  - The delayed plantar reflex (DPR) is a pathologic flexor variant which requires
      unusually strong stimulation of the sole of the foot and is characterized by a
      prolonged interval between the stimulus and the response, slow and protracted
      plantarflexion of the great toe and/or other toes and slow return to the neutral
      position. The purpose of this study was to evaluate prospectively the functional
      outcome of spinal cord injury (SCI) patients based on the presence or absence of
      a DPR immediately following injury. Thirty-six subjects were evaluated within one
      week of injury. A complete neurological evaluation following American Spinal
      Injury Association (ASIA) standards was performed and the presence or absence of
      a DPR was noted on admission. Ambulation status and ASIA Impairment Scales were
      recorded at discharge from the rehabilitation unit and the data were analyzed by
      the Chi-square method with Yates' correction for continuity. The data
      demonstrated a high correlation of the DPR with motor complete injuries (p <
      0.01) and a poor prognosis for recovery of ambulation (p < 0.01). Clinicians
      should recognize this abnormal reflex, which may be used in conjunction with a
      complete neurological examination, to help prognosticate future function in the
      acute SCI patient.

PMID- 9144611
TI  - Orthostatic hypotension in spinal cord injured patients.
AB  - Treatment of orthostatic hypotension is an important consideration for many
      patients with spinal cord injuries, especially those with an injury to the
      cervical cord. Delay in attainment of an upright sitting posture can cause a
      delay in the completion of rehabilitation. Although most trials of medications
      used in the treatment of orthostatic hypotension have been performed on non
      spinal cord injured patients, this paper provides a review of both
      pharmacological and non-pharmacologic means of therapy. Normally, regulation of
      mean arterial pressure occurs through several different mechanisms; long-term
      control is via the renal system and short-term control is via the nervous system.
      These mechanisms will be discussed, as well as causes of orthostatic hypotension
      in spinal cord injured patients, and the normalization of blood pressure control
      which generally occurs to some degree following a spinal cord injury.

PMID- 9144612
TI  - Micturition by functional magnetic stimulation.
AB  - Effectiveness of functional magnetic stimulation (FMS) technology on bladder
      contraction and bladder emptying was evaluated in twenty-two spinal cord injured
      subjects. FMS of the bladder was performed by stimulating the sacral nerves or
      the suprapubic region using a commercially available magnetic stimulator with a
      round coli. With sacral stimulation, the mean change in bladder pressure (Pves)
      was 24.4 +/- 4.88 cm H2O; with suprapubic stimulation, the mean change in Pves
      was 16.5 +/- 4.44 cm H2O. The change in Pves with sacral stimulation was higher
      than with suprapubic stimulation (p < .01). Seventeen subjects demonstrated
      voiding, either with sacral or suprapubic stimulation. Using a water-cooled coli,
      one subject demonstrated complete bladder emptying. FMS of the bladder has the
      potential to be a useful non-invasive technology for bladder emptying and bladder
      training in patients with neurogenic bladders.

PMID- 9144613
TI  - Improved bowel care with a polyethylene glycol based bisacadyl suppository.
AB  - To test its effectiveness for bowel care in myopathy patients, a bisacodyl
      suppository based in polyethylene glycol (PEGBS) was compared with a conventional
      bisacodyl suppository based in hydrogenated vegetable oil (HVOBS). Nineteen
      patients with upper motor neuron paralysis received 57 HVOBS and 114 PEGBS trials
      in a crossover design. The average time for complete bowel evacuation was 2.4
      (range 1.0 to 4.5) hours with HVOBS and 1.1 (range 0.3 to 1.8) hours with PEGBS.
      Three patients later discontinued the PEGBS because of cramps or fecal
      incontinence. The remaining 16 patients continued to use PEGBS for three years
      and 15 reported a sustained savings in time. It is concluded that the replacement
      of HVOBS with PEGBS will reduce bowel care time in myelopathy patients by about
      half.

PMID- 9144614
TI  - A case of central cord syndrome caused by intubation: a case report.
AB  - Following intubation for respiratory distress, a 42 year-old female patient
      sustained a hyperextension injury which produced a central cord syndrome. This
      paper illustrates an unusual mechanism whereby a central cord syndrome was caused
      by pure hyperextension without high velocity force.

PMID- 9144615
TI  - Multielectrode nerve cuff stimulation of the median nerve produces selective
      movements in a raccoon animal model.
AB  - In this study, an electrode system consisting of twelve small platinum dot
      electrodes imbedded in a spiral silicone rubber insulating cuff was used to
      investigate the feasibility of selective (regional) stimulation of the median
      nerves of the raccoon. Acute experiments in four raccoons consisted of functional
      responses observations, isometric force recordings from tendon attachments and
      postmortem fascicular mapping. Functional responses (elbow, wrist and/or digit
      flexion, pronation and/or thumb abduction) to selective stimulation were noted as
      dependent upon cuff electrode configuration (longitudinal tripole with and
      without field steering, as well as a transverse bipolar arrangement) and current
      level (threshold, 1/2 maximal, maximal). Muscle force recruitment curves (force
      as a function of stimulus amplitude) were plotted for flexor digitorum
      superficialis, flexor digitorum profundus, flexor carpi radialis, palmaris longus
      and pronator teres of three raccoons. Fascicular maps at the level of the nerve
      cuff were created indicating the approximate position of innervation to each of
      the aforementioned muscles, as well as other innervation such as paw fascicles,
      sensory fascicles, and elbow innervation (such as coracobrachialis). The greatest
      selectivity was observed at or near threshold current levels. In all four
      raccoons studied, a threshold electrode choice and stimulation strategy could be
      identified enabling selective production of either digit flexion, wrist flexion
      and/or digit and wrist flexion. It was possible to elicit a selective pronation
      response at threshold in three of the four animals. Selective elbow flexion at
      threshold could be produced in all four experiments. With stronger currents,
      additional movements were usually induced. The raccoon therefore appears to be a
      suitable, if challenging, animal model for further development of not only nerve
      cuff electrode approaches but perhaps other stimulation electrode technologies
      prior to human neuroprosthetic studies.

PMID- 9144616
TI  - Mucinous adenocarcinoma arising from a suprapubic cystostomy site without bladder
      involvement.
AB  - Carcinoma arising from a suprapubic cystostomy site in patients with spinal cord
      injury has been infrequently described. In all previously reported cases, they
      have been squamous cell carcinomas. Our patient is a 68 year old male with T10
      complete thoracic paraplegia who presented with an exophytic mass extending from
      his suprapubic cystostomy tract. Biopsy revealed mucinous adenocarcinoma.
      Carcinoma of the suprapubic cystostomy tract should be considered in those
      patients who present with bloody drainage and/or masses arising from the
      suprapubic cystostomy site.

PMID- 9144617
TI  - Introduction to pulmonary neuroendocrine cell system, structure-function
      correlations.

PMID- 9144618
TI  - Paraneurons in the gills and airways of fishes.
AB  - This chapter describes the distributional patterns of the neuroendocrine cells in
      the respiratory surfaces of fishes and their bioactive secretions which are
      compared with similar elements in higher vertebrates. The neuroendocrine cells in
      the airways of fishes differentiate as solitary and clustered cells, but the
      clusters are not converted into neuroepithelial bodies which are reported in
      terrestrial vertebrates. The dipnoan fish Protopterus has innervated
      neuroendocrine cells in the pneumatic duct region. In Polypterus and Amia the
      lungs have neuroendocrine cells that are apparently not innervated. Two types of
      neuroendocrine cells are found in the gill of teleost fishes. These cells are
      very different by their location, structure and immunohistochemistry. Advanced
      studies on functional morphology of neuroendocrine cells in fish airways are
      still necessary to increase our understanding of their multifunctional role in
      the gill area.

PMID- 9144619
TI  - Neuroepithelial bodies and solitary neuroendocrine cells in the lungs of
      amphibia.
AB  - In the lungs of 12 species of Amphibia investigated so far, solitary
      neuroendocrine (NE) cells, as well as groups of these cells called
      "neuroepithelial bodies" (NEB), are observed. They occur in the position
      strategic to monitoring gas composition, mainly in the ciliated epithelium of the
      apical part of the septa. A great diversity in the structure of NEB is observed.
      The NE cells and NEB in Amphibia are predominantly of the "closed type,"
      separated from the air space by a thin cytoplasmic layer of ciliated cells,
      goblet cells or pneumocytes. In two species, Bufo marinus and Ambystoma tigrinum,
      the "open type" of NEB occur, where NEB communicate with the air space, by apical
      cells in Bufo and type II NE cells in Ambystoma. Both types of cells possess
      single atypical cilia with an 8+1 microtubule arrangement and microvilli on the
      free surface. Single and grouped NE cells are characterized by small dense core
      vesicles (DCV) dispersed in the cytoplasm. In Salamandra and Ambystoma the second
      type of NE cells with large DCV are observed. The DCV represent sites of storage
      of serotonin and several neuropeptides. The basal parts of NEB and of some
      solitary cells are invested by the intraepithelial sensory nerve terminals, both
      afferent and efferent morphologically. In the lungs of Amphibia, similarly to
      other vertebrates, NE cells, which act as endocrine/paracrine receptors, form
      epithelial endocrine systems.

PMID- 9144620
TI  - Comparative histology of pulmonary neuroendocrine cell system in mammalian lungs.
AB  - It is increasingly recognized that neuroepithelial endocrine cells and organoid
      clusters of these cells termed neuroepithelial bodies are widely distributed in
      the respiratory tract of vertebrates. This review focuses on the neuroepithelial
      endocrine system in the airway epithelium of mammals according to observations
      made in a wide range of species, as it appears in light and electron microscopy
      by means of various visualization techniques under normal and experimental
      conditions. Because there are similarities but also marked differences between
      species, wherever possible studies in human airways are emphasized. Conventional
      histochemical and ultrastructural studies including microspectrofluorimetry have
      demonstrated the amine-handling properties and the presence of neurosecretory
      granules in neuroendocrine cells of the epithelium of all mammals studies so far.
      The neuroepithelial bodies are innervated by morphological afferent- and
      efferentlike synaptic specializations. These, together with the presence of
      reciprocal synapses, emphasize that these cells may be involved in dual functions
      of chemoreception and secretion. Light and electron microscopic
      immunohistochemistry has demonstrated that neuroepithelial endocrine cells may
      contain various biogenic agents, suggesting that the neuroendocrine system is
      highly heterogeneous. Neural elements may interact in a complex manner, and the
      activation of certain neural pathways may control the release of biogenic
      substances to influence physiological airway functions. They may be particularly
      relevant in pulmonary diseases. Consequently, the function of this system is
      complex and it is highly probable that many of its aspects are still not
      elucidated.

PMID- 9144621
TI  - Ontogeny of neuroepithelial bodies: correlations with mitogenesis and
      innervation.
AB  - This paper summarizes current knowledge and advances speculation about the
      formation of the neuroendocrine system of mammalian lungs (comprising
      uninnervated solitary and clustered small-granule cells and innervated
      neuroepithelial bodies). It relates the initial appearance of neuroendocrine
      cells to regulation of mitotic activity in the epithelium during the development
      of the lung and pays special attention to the later in growth of nerves that
      converts some of them into neuroepithelial bodies, structures considered ideally
      adapted to function as chemoreceptors. A few original observations from ongoing
      immunohistochemical, electron microscopic, and analytical studies have been
      included here and there to point the discussion. The neuroendocrine cells are
      derived from undifferentiated precursors present in the endodermal pulmonary
      epithelium. At an early pseudoglandular stage of lung development these
      precursors begin to differentiate into neuroendocrine small-granule cells,
      commencing in the larynx and upper trachea, and expanding centrifugally into
      pulmonary airways almost as rapidly as these are laid down. Subsequently many of
      the intrapulmonary small-granule cell clusters become innervated. This event, the
      delayed appearance of small-granule cells synthesizing other than the dominant
      peptides and amines (calcitonin gene-related peptide and serotonin in rodents,
      gastrin-releasing peptide and serotonin in human beings), and other regional
      adjustments yield the population distribution present in the lungs of adults.
      Neuroendocrine cell precursors normally differentiate into typical serotonin- or
      peptide-synthesizing small-granule cells without requiring direct contact by
      nerves, and dissociated cells from a previously innervated population continue to
      exhibit physiological characteristics of oxygen sensors despite the loss of
      contact with nerves. Development of the innervation occurs in stages. Small
      granule cell clusters are reached first by ganglion cells derived from pulmonary
      neuroblasts and later on by processes of extrinsic sensory nerves. The latter not
      only convey information to the central nervous system but also serve in a variety
      of ways to extend the neuroepithelial bodies' sphere of influence within the lung
      itself.

PMID- 9144622
TI  - Comparison of the ontogeny of protein gene product 9.5, chromogranin A and
      proliferating cell nuclear antigen in developing human lung.
AB  - Pulmonary neuroendocrine cell products, especially bombesin-like peptides, are
      important modulators of fetal lung growth, morphogenesis and maturation. In the
      present study, we describe the ontogeny of protein gene product 9.5 (PGP 9.5) in
      28 midtrimester human fetal lungs, in comparison to chromogranin A (CGA), a
      marker of differentiated neuroendocrine cells, and proliferating cell nuclear
      antigen (PCNA), which is expressed by actively dividing cells. PGP 9.5
      immunostaining colocalized with CGA in many cells, although the peak abundance of
      PGP 9.5 preceded that of CGA by 4 to 6 weeks. In addition, a novel staining
      pattern was noted for PGP 9.5: diffuse cytoplasmic staining of undifferentiated
      epithelial cells, which was demonstrated by all of the airways before 15 weeks
      gestation. After gestational week 15, only the smallest airways demonstrated this
      pattern. PCNA immunostaining demonstrated age-dependent regional variation. All
      samples had approximately 25% epithelial cells immunopositive for PCNA. Between
      11 and 14 weeks gestation over 50% of the mesenchymal cells were PCNA positive.
      This mesenchymal staining decreased after 14 weeks, and was rare by week 19.
      There was no definite correlation between the immunostaining for PGP 9.5 and that
      for PCNA, although PGP 9.5 positive cells were usually PCNA negative. These
      observations suggest that other growth factors produced by non-neuroendocrine
      epithelial cells also participate in lung development.

PMID- 9144623
TI  - NCAM expression in the pulmonary neural and diffuse neuroendocrine cell system.
AB  - Neural cell adhesion molecule (NCAM)--a membrane protein involved in cell-cell
      adhesion within the central and peripheral nervous systems--was demonstrated to
      be a sensitive and specific marker for neuroepithelial bodies (NEB) and neural
      tissue elements in the cat lung. Using the streptavidin-biotin immunoperoxidase
      method, NCAM reactive sites were investigated with monoclonal and polyclonal
      antibodies on serial section of Bouin fixed, paraffin embedded lung tissue.
      Moreover, NCAM expression was compared with that of neuron-specific enolase (NSE)
      on adjacent sections. The most obvious NCAM staining was obtained with the
      monoclonal antibody. From newborn to adult life, cell surface labeling was
      identified on NEB cells. In mature cat lung, they were no longer positive.
      Solitary neuroendocrine cells (NEC) were always negative. In contrast to the
      transient postnatal immunoreactivity of NEB cells, nerve fibers and ganglion
      cells were stained throughout all life stages and studied. The distribution of
      NCAM in NEB, nerve fibers and ganglion cells was similar to that NSE, except in
      the adult lung. This study reveals that during lung growth shared NCAM antigens
      exist between the pulmonary nervous and endocrine system, whereas in mature lung
      NCAM proteins are confined to neural tissue elements. The difference in NCAM
      expression between NEB and NEC might suggest an involvement of NCAM in the
      formation of contacts between NEB cells and nerves.

PMID- 9144624
TI  - Immunogold EM localization of neurochemicals in human pulmonary neuroendocrine
      cells.
AB  - Antibodies against the pulmonary neuroendocrine cell peptides gastrin-releasing
      peptide (bombesin), calcitonin and calcitonin gene-related peptide (CGRP) have
      been labeled with colloidal gold spheres for immunocytochemical localization in
      human fetal and newborn lung tissue. In general, the presence and amount of
      immunolabeling increased with increasing gestational age, with only calcitonin
      appearing late in fetal life. The largest percentage of neuroepithelial body
      (NEB) cells labeled and the largest number of labeled dense core vesicles (DCV)
      were in infants with chronic lung disease (bronchopulmonary dysplasia). Serial
      ribbons allowed identification of more than one peptide in a single NEB cell. The
      use of two antibodies labeled with colloidal gold spheres of different sizes
      allowed the identification of two peptides in the same DCV. Quantification of
      relative amounts of labeled peptides was not possible, as the peptide labeling
      with the larger size gold sphere was consistently underestimated. Colocalization
      to the same DCV has been shown in humans for bombesin and calcitonin, calcitonin
      and CGRP, bombesin and CGRP and, by others for cholecystokinin (CCK) and
      serotonin. Colocalization of two or more peptides or an amine to a single DCV
      within the same cell implies simultaneous discharge by exocytosis. The action of
      the two (or more) substances might be in concert, perhaps with one acting in a
      paracrine fashion, and the second in an autocrine fashion. In this case, the
      second peptide or amine might have a regulatory function in the parent cell,
      influencing DCV storage or rate of release.

PMID- 9144625
TI  - Quantitative microscopical methods for the identification and localisation of
      nerves and neuroendocrine cell markers in mammalian lung.
AB  - The lung contains a dense innervation and a population of endocrinelike cells
      both of which are believed to have a role in pulmonary function and to be
      involved in disease processes. They contain a number of regulatory peptides that
      affect vascular and bronchial tone, growth and repair. They can be detected and
      localised by immunocytochemistry, thereby allowing investigation of the normal
      distribution and changes in disease processes. The application of image analysis
      has added greatly to the amount of information that can be obtained from such
      morphological studies. Data can be obtained on either the overall distribution
      and amount of the antigen in a tissue, thereby allowing comparisons between
      normal and disease states, or following experimental manipulation. Furthermore,
      the actual intracellular level can be assessed, which adds the previously
      unattained dimension of comparisons between cells. Thus the density of
      innervation in the specific regions of the lung tissue, either total nerves or
      specific peptide-containing cells, may be estimated and used to show release of a
      peptide or to determine changes in the nerve density in disease. Image processing
      and image analysis have reduced the labour-intensive manual input required to
      perform such studies. The continuing development of digital image processing and
      computer technology will increase the application of these methods in lung
      research of normal and pathological material.

PMID- 9144626
TI  - Immunocytochemical localization on O2-sensing protein (NADPH oxidase) in
      chemoreceptor cells.
AB  - A potential candidate for an oxygen-sensing protein in chemoreceptor cells is a
      heme-linked multicomponent NADPH oxidase, originally described in neutrophils.
      The postulated function for the oxidase in chemoreceptor cells is to signal
      changes in oxygen levels (either in the blood or in the airway lumen) via changes
      in oxygen metabolite production. An alteration in either superoxide (or dismuted
      hydrogen peroxide) production may affect the gating properties of the O2
      sensitive K+ channels. We have previously reported immunohistochemical
      localization of gp91 glycoprotein component of the oxidase to the plasma membrane
      of pulmonary neuroepithelial body (NEB) cells. In this study we have investigated
      the immunocytochemical localization of the other polypeptide components of the
      oxidase in NEB cells and in the glomus cells of the carotid body. Cultures of
      dissociated fetal rabbit NEB cells and newborn rat glomus cells were
      immunostained with specific antibodies recognizing the various polypeptide
      subunits of the oxidase using indirect immunofluorescence methods. Immunostaining
      with the anti-oxidase antibodies reveal strong positive reaction in both NEB and
      glomus cell clusters while other cells were unstained. The positive reaction
      product was localized to the plasma membrane and/or cytoplasm and no nuclear
      staining was observed. Live cell labelling studies with anti-p22 antibody showed
      positive immunofluorescence on the surface of NEB cells, suggesting that this
      component of the oxidase is also associated with the plasma membrane. In glomus
      cells, similar strongly positive immunofluorescence signal was observed for p22
      and gp91 in paraformaldehyde-fixed cultures, regardless whether they were
      permeabilized or not. Taken together, our findings of cell surface localization
      of gp91 and p22 components of the oxidase in chemoreceptive cells suggests that
      the heme-linked cytochrome b558 component is associated with the plasma membrane.
      This association allows for direct interaction with the O2-sensitive K+ channel
      thus forming the molecular complex of membrane bound O2 sensor.

PMID- 9144628
TI  - Introduction to histological aspects of dermatotoxicology.

PMID- 9144627
TI  - Pulmonary neuroendocrine cell system in pediatric and adult lung disease.
AB  - In humans lungs affected by naturally occurring pulmonary disease, the pulmonary
      neuroendocrine cell system, which is normally arranged in a sparse but even
      distribution throughout the respiratory tract, increases in size. It is likely
      that the stimulus for this is pulmonary injury and that its purpose is the
      paracrine regulation of the restoration of pulmonary tissues to their normal
      state, an hypothesis supported by studies of animal lungs subjected to
      experimental injury as well as of the development of human and animal lungs in
      utero. Initially, this increase involves the development of interrupted rows of
      neuroendocrine cells. In the later stages, however, development of more
      disorderly intraepithelial aggregates can occur and the small, locally invasive
      neuroendocrine cell lesions known as tumourlets may occasionally result. Both of
      these latter structures often contain secretory products not found in the
      neuroendocrine cells of normal human lungs, probably indicating a derangement of
      what appears to be a fundamentally physiological response. It is likely that, in
      some circumstances, this disorderly change may contribute to pulmonary disease as
      well as being the result of it.

PMID- 9144629
TI  - Comparison of an in vitro skin model to normal human skin for dermatological
      research.
AB  - EpiDerm, an in vitro human skin equivalent (HSE), was compared to normal human
      breast skin (NHS) to morphologically and biochemically assess its feasibility for
      dermatological research. Intralot and interlot variability was studied in day 0,
      1, 2, and 3 in vitro cultures and in day 0, 3, 5, and 7 NHS. For NHS, light
      microscopy (LM) at day 0 showed stratified epidermis which exhibited an increase
      in vacuoles and dark basal cells as storage increased to 3, 5, and 7 days.
      Transmission electron microscopy (TEM) revealed typical organelles in the
      epidermis and a convoluted basement membrane at day 0. With increased storage,
      vacuoles and paranuclear clefts became numerous, necrosis increased,
      tonofilaments became less organized, and overall cellular integrity decreased.
      Biochemical data showed consistent MTT and glucose utilization (GU) through day
      5, while lactate production decreased to 75% by day 3. By LM, day 0 HSE consisted
      of a thick, compact, stratum corneum that sent projections between the stratum
      granulosum cells. By TEM, the configuration organization, differentiation,
      distribution, and frequency of the organelles differed slightly from NHS. In
      addition, the basement membrane of the HSE was not completely differentiated, and
      the dermis was thin and acellular. Although day 1 and 2 cultures showed little
      change, day 3 exhibited an overall degeneration. Biochemical analysis showed GU
      and the lactate production decreased through day 3. In conclusion, the EpiDerm
      HSE, although exhibiting slight differences, was morphologically and
      biochemically similar to normal human epidermis and may be a valuable model in
      assessing the toxicology, metabolism, or pharmacology of nonvesicating compounds.

PMID- 9144630
TI  - Morphology of lipid alterations in the epidermis: a review.
AB  - An overview of the morphological correlates of mammalian epidermal lipids and the
      cutaneous permeability barrier is provided. The following features are discussed:
      1) ultrastructural characterization of the progressive lipid alterations
      accompanying normal stratum corneum (SC) formation; 2) effects of
      drugs/inhibitors that interfere with specific aspects of epidermal lipid
      metabolism; 3) lipid alterations in certain human skin disorders; 4) effects of
      selected topical emollients on SC lipid organization; and 5) potential pitfalls
      in interpretation of ultrastructural data in terms of cutaneous function and
      dysfunction.

PMID- 9144631
TI  - Ultrastructure of the epidermal barrier after irritation.
AB  - The stratum corneum (SC) controls the diffusion and penetration of chemical
      substances and drugs into and through the skin. Surprisingly, knowledge of the SC
      structure and reaction to the various irritants is still poorly understood.
      Routine transmission electron microscopy has not been effective in demonstrating
      the epidermal lipids (EL) of SC which are believed to morphologically represent
      the water permeability barrier. To gain a better understanding of the interaction
      of chemically different irritants with the SC, we investigated the
      ultrastructural changes of epidermal lipids resulting from the topical
      application of sodium dodecyl sulfate (SDS 0.5% and 1% w/v) and absolute acetone.
      The disturbance of barrier function by these irritants was determined by the
      increase of transepidermal water loss (TEWL). Punch biopsies from the treated
      sites showed a maximum increase of TEWL. To visualize the EL which derive from
      lamellar body (LB) lipids (sheets), we used a special fixation method utilizing
      0.5% ruthenium tetroxide/0.25% KFe(CN)6 as the postfixative. The 0.5% SDS caused
      cell damage to the nucleated cells of the epidermis with disturbance of LB lipid
      extrusion and the transformation into the lipid bilayers. However, the upper
      portions of SC displayed intact intercellular lipid layers. With the acetone
      treatment, the EL lamellae showed disruption and loss of cohesion between the
      lamellae at all levels of the SC. The more polar LB lipids appeared more
      resistant to acetone. The results of this study suggest that different irritants
      induce distinct and characteristic alterations to reflect the specific
      interaction with the epidermal permeability barrier.

PMID- 9144632
TI  - Electroperturbation of the human skin barrier in vitro: II. Effects on stratum
      corneum lipid ordering and ultrastructure.
AB  - In transdermal iontophoresis, drugs can be driven across the skin by
      electrorepulsion, but their transport can also be enhanced by electrical
      perturbation of the skin barrier. Our objective was to study perturbing effects
      of electrical current on human stratum corneum lipid fine structure combining
      techniques including freeze-fracture electron microscopy. Human stratum corneum
      was subjected to pulsed constant currents, varying from 0.013-13 mA.cm-2. The
      voltage across the stratum corneum was high-frequency-sampled and s.c. impedence
      values derived from it. Upon termination of the current, skin samples were
      rapidly frozen and processed for freeze-fracture electron microscopy or subjected
      to X-ray diffraction analysis. Initially a rapid decrease of the resistance and,
      overall, a rapid increase of the capacitances was observed; generally, these
      effects became more pronounced with increasing current density. Wide- and small
      angle X-ray diffractograms of human stratum corneum exposed for 1 h to the
      highest current indicated a disordering of both the lateral packaging arrangement
      and long-range lamellar stacking of the intercellular lipids of stratum corneum.
      Furthermore, an increase in the stratum corneum hydration level as a result of
      electrical current application was observed. On electron micrographs of freeze
      fracture replicas of human stratum corneum, exposed for 1 h to current densities
      between 0.013 and 13 mA.cm-2, perturbations of the intercellular lipid structure
      were observed in accordance with the results of X-ray diffraction; these
      perturbations aggravated with increasing current density. Together, the data
      suggest that both the lateral and the longitudinal disordering of the
      intercellular lipids observed with X-ray diffraction may be responsible for the
      appearance of perturbed structures observed with freeze-fracture electron
      microscopy. The lipid disordering may be due to polarization of the lipid head
      groups induced by the electrical field, followed by mutual repulsion.

PMID- 9144633
TI  - Inflammatory damage to skin by prolonged contact with 1,2-dichlorobenzene and
      chloropentafluorobenzene.
AB  - Skin samples from Fischer-344 rats and Hartley guinea pigs exposed dermally to
      1,2-dichlorobenzene (DCB) and chloropentafluorobenzene (CPFB) for up to 4 h were
      examined for chemical-induced damage. Samples were stained with hematoxylin and
      eosin and scored for polymorphonuclear cell (PMN) margination, dermal
      inflammation, and epidermal necrosis by light microscopy. Ultrastructural
      evaluation of samples fixed with 2% glutaraldehyde and postfixed with 1% osmium
      tetroxide was used to visualize margination of PMNs. Guinea pigs exhibited
      postexposure inflammatory changes following an exposure of about an hour-and-a
      half shorter duration than rats. DCB-induced inflammation and PMN margination
      occurred following an exposure about a half hour shorter in both species compared
      to CPFB. In contrast, epidermal necrosis was more severe with CPFB than with DCB.
      These changes may account for decreases in chemical penetration rates which have
      been observed in previous studies with DCB and CPFB in rats and guinea pigs.

PMID- 9144634
TI  - Toxicity of mustard gas skin lesions.
AB  - Although the exact pathogenesis of mustard gas-induced dermal toxicity remains
      elusive, morphopathological data gathered in controlled animal and in vitro
      investigations is providing important clues as to approximate mechanisms. Our
      laboratory has been studying dermal effects of the chemical warfare agent, sulfur
      mustard, in a variety of animal models, cultured isolated human cells, and in
      vitro organotypic skin models. Published anatomical, pathological, and
      ultrastructural results of these studies have documented consistent cellular and
      basement membrane zone effects irrespective of the model. Cellular effects
      include the early targeting of basal cells of the stratum basale to the exclusion
      of other epidermal cells, with nuclear and cytoplasmic indications of cell injury
      and cell death. Effects on the basement membrane zone include the formation of
      characteristic microvesicles in the lamina lucida of those models which possessed
      structural components of a true basement membrane. We are now investigating
      effects on proteins of the basement membrane microenvironment and correlate in
      the present paper the morphopathology of sulfur mustard dermal lesions with
      immunohistochemical study of bullous pemphigoid antigen, laminin, type IV
      collagen, and type VII collagen.

PMID- 9144635
TI  - Ultrastructural characterization of sulfur mustard-induced vesication in isolated
      perfused porcine skin.
AB  - The isolated perfused porcine skin flap (IPPSF) is a novel alternative, humane in
      vitro model consisting of a viable epidermis and dermis with a functional
      microvasculature. For this study, 200 microliters of either 10.0, 5.0, 2.5, 1.25,
      0.50, or 0.20 mg/ml of bis (2-chloroethyl) sulfide (HD) in ethanol or ethanol
      control was topically applied to a 5.0 cm2 dosing area of the IPPSF and perfused
      for 8 h with recirculating media. HD dermatotoxicity was assessed in the flap by
      cumulative glucose utilization (CGU), vascular resistance (VR), light microscopy
      (LM), scanning electron microscopy (SEM), and transmission electron microscopy
      (TEM). HD produced a statistically significant dose relationship for gross
      blisters and microvesicles. The HD-treated IPPSFs were also characterized by a
      decrease in CGU and an increase in VR. Light microscopic changes included mild
      intracellular and slight intracellular epidermal edema, multifocal epidermal
      dermal separation, and dark basal cells. Ultrastructural alterations consisted of
      cytoplasmic vacuoles, pyknotic basal cells, nucleolar segregation, and epidermal
      dermal separation occurring between the lamina lucida and lamina densa of the
      basement membrane. The severity of these changes increased in a dose-dependent
      manner. Morphologically, the IPPSF appeared similar to human skin exposed to HD
      with the formation of macroscopic blisters and microscopic vesicles. In
      conclusion, the IPPSF appears to be an appropriate in vitro model with which to
      study the pathogenesis of vesicant-induced toxicity.

PMID- 9144636
TI  - LY354740 is a potent and highly selective group II metabotropic glutamate
      receptor agonist in cells expressing human glutamate receptors.
AB  - The novel compound LY354740 is a conformationally constrained analog of
      glutamate, which was designed for interaction at metabotropic glutamate (mGlu)
      receptors. In this paper the selectivity of LY354740 for recombinant human mGlu
      receptor subtypes expressed in non-neuronal (RGT) cells is described. At human
      mGlu2 receptors, LY354740 produced > 90% suppression of forskolin-stimulated cAMP
      formation with an EC50 of 5.1 +/- 0.3 nM. LY354740 was six-fold less potent in
      activating human mGlu3 receptors (EC50 = 24.3 +/- 0.5 nM). LY354740 inhibition of
      forskolin-stimulated cAMP formation in human mGlu2 receptor-expressing cells was
      blocked by competitive mGlu receptor antagonists, including (+)-alpha-methyl-4
      carboxyphenylglycine (MCPG) and LY307452 ((2S,4S)-2-amino-4-(4,4-diphenylbut-1
      yl)-pentane-1,5-dioic acid). LY354740 had no agonist or antagonist activities at
      cells expressing human mGlu4 or mGlu7 (group III mGlu receptors) (EC50 > 100,000
      nM). When tested at group I phosphoinositide-coupled human mGlu receptors (mGlu1a
      and mGlu5a), LY354740 did not activate or inhibit mGlu receptor agonist-evoked
      phosphoinositide hydrolysis at up to 100,000 nM. Electrophysiological experiments
      also demonstrated that LY354740 also had no appreciable activity in cells
      expressing human recombinant AMPA (GluR4) and kainate (GluR6) receptors. Thus,
      LY354740 is a highly potent, efficacious and selective group II (mGlu2/3)
      receptor agonist, useful to explore the functions of these receptors in situ.

PMID- 9144638
TI  - Cloning and characterization of a metabotropic glutamate receptor, mGluR4b.
AB  - An alternative spliced variant of metabotropic glutamate receptor subtype
      mGluR4a, termed mGluR4b was isolated from a rat cDNA library. Subtype mGluR4b was
      identical to the previously described mGluR4a, except for the last 64 amino acids
      in the C-terminal region in which were replaced by 135 new amino acids in
      mGluR4b. Recombinant baculoviruses coding for mGluR4a and mGluR4b were expressed
      in Spodoptera frugiperda, Sf-9, insect cells and characterized pharmacologically
      by measuring [3H]-L-2-amino-4-phosphonobutyrate ([3H]-L-AP4) binding and second
      messenger formation. [3H]-L-AP4 binding to membranes prepared from Sf-9 cells
      expressing mGluR4a and mGluR4b revealed respective affinities (Kd) of 480 and 360
      nM and maximal binding densities (Bmax) of 4.2 and 0.8 pmol/mg protein. The
      ligand selectivity of mGluR4a and mGluR4b was similar: L-AP4 > L-serine-O
      phosphate > L-glutamate > L-2-amino 2-methyl-4-phosphonobutyrate > (1S,3R)-1
      aminocyclopentane-1,3-dicarboxylate > or = quisqualate. A decrease in the
      affinity of [3H]-L-AP4 was observed in the presence of 0.1 mM guanosine 5'-O-(3
      thio)trisphosphate-gamma-S, indicating that mGluR4a and mGluR4b were functionally
      coupled to G-proteins in Sf-9 cells. Agonists of mGluR4 caused a minor decrease
      in forskolin-induced cAMP formation in Sf-9 cells expressing either mGluR4a or
      mGluR4b, suggesting that both receptors are coupled to adenylate cyclase in an
      inhibitory manner. Thus, mGluR4a and mGluR4b share a common signal transduction
      pathway and pharmacology when expressed in Sf-9 insect cells.

PMID- 9144637
TI  - Two phenylglycine derivatives antagonize responses to L-AP4 in ON bipolar cells
      of the amphibian retina.
AB  - Light responses of retinal ON bipolar cells are mediated by metabotropic
      glutamate receptors selectively activated by L-2-amino-4-phosphonobutyric acid (L
      AP4). Antagonists to L-AP4 receptors in ON bipolar cells have not previously been
      identified. This study examines the electrophysiological effects of (S)-2-amino-2
      methyl-4-phosphonobutanoic acid (MAP4), (RS)-4-4-chloro-3,5
      dihydroxyphenylglycine (CDHPG) and (RS)-3,4,5-trihydroxyphenylglycine (THPG), at
      L-AP4 receptors in ON bipolar cells of the amphibian retina. Unlike its actions
      in spinal cord, in retinal ON bipolar cells MAP4 is a weak agonist which exhibits
      no detectable antagonism to L-AP4. On the other hand, CDHPG exhibits a mixture of
      agonist and antagonist properties. Addition of Co2+ and oxygenation of CDHPG
      turns the solution brown and enhances antagonist effects, suggesting that the
      antagonism reflects actions of a breakdown product of CDHPG. Although THPG did
      not prove to be this breakdown product, it also has electrophysiological effects
      consistent with an L-AP4 receptor antagonist. The results suggest that THPG and
      breakdown products of CDHPG may be antagonists to L-AP4 receptors in retinal ON
      bipolar cells, although the possibility that these compounds antagonize effects
      of L-AP4 by acting at some site in the transduction pathway of L-AP4 receptors
      cannot yet be excluded.

PMID- 9144639
TI  - Antidepressant-like effects of a partial agonist at strychnine-insensitive
      glycine receptors and a competitive NMDA receptor antagonist.
AB  - Using the forced swimming test in rats (Porsolt test), we examined the
      antidepressant-like activity of 1-aminocyclopropanecarboxylic acid (ACPC), a
      partial agonist at strychnine-insensitive glycine receptors associated with the N
      methyl-D-aspartate (NMDA) receptor complex, and of DL-(E)-2-amino-4-methyl-5
      phosphono-3-pentenoic acid (CGP 37849), a competitive NMDA receptor antagonist,
      after their intraperitoneal (i.p.) and intrahippocampal (i.hp.) administration.
      ACPC (200-400 mg/kg) and CGP 37849 (0.625-5 mg/kg), administered i.p., produced a
      dose-dependent and significant reduction of the immobility time in the forced
      swimming test. A similar effect was also observed in i.hp. administration of ACPC
      (10 and 30 micrograms) and CGP 37849 (0.03 and 0.1 micrograms). Imipramine, used
      as a reference drug, significantly shortened the immobility time after both i.p.
      (30 and 40 mg/kg) and i.hp (0.1 and 0.3 micrograms) administration. The compounds
      studied, administered in doses effective in the forced swimming test, did not
      change the exploratory activity of the rats, evaluated by an open field test. The
      present results indicate that, like imipramine, ACPC and CGP 37849 exhibit an
      antidepressant-like activity in the forced swimming test in rats; moreover, they
      seem to show the hippocampus may be one of the neuroanatomical sites involved in
      this effect.

PMID- 9144640
TI  - Effects of lobeline and dimethylphenylpiperazinium iodide (DMPP) on N-methyl-D
      aspartate (NMDA)-evoked acetylcholine release in vitro: evidence for a lack of
      involvement of classical neuronal nicotinic acetylcholine receptors.
AB  - Biochemical, behavioral and electrophysiological evidence suggests interactions
      between pathways containing neuronal nicotinic acetylcholine receptors (NAChRs)
      and excitatory amino acid receptors. Recently, protective effects of nicotine
      against N-methyl-D-aspartate (NMDA)-induced toxicity in primary cortical cultures
      were reported. To address possible interactions between NAChR and NMDA receptor
      containing pathways, several NAChR agonists were evaluated for their effects on
      NMDA-evoked [3H]acetylcholine ([3H]ACh) release from slices of rat striatum.
      Nicotine, cytisine and epibatidine had no effect on NMDA-evoked release or basal
      release of [3H]ACh over a wide range of concentrations. Lobeline and
      dimethylphenylpiperazinium iodide (DMPP), however, decreased basal [3H]ACh
      release and attenuated NMDA-evoked [3H]ACh release with EC50 values of 35 and 155
      microM, respectively. The NAChR antagonists, dihydro-beta-erythroidine (DH beta
      E) and d-tubocurarine had no effect on NMDA-evoked [3H]ACh release, whereas
      mecamylamine attenuated the NMDA-evoked [3H]ACh evoked release with an EC50 value
      of 144 microM. Methyllycaconitine (MLA), a highly selective and potent antagonist
      of the alpha-bungarotoxin-sensitive alpha 7 NAChR subtype, also had no effect on
      NMDA-evoked [3H]ACh release at concentrations upto 10 microM. The inhibitory
      effects of DMPP and lobeline on NMDA-evoked [3H[ACh release were relatively
      insensitive to mecamylamine, d-tubocurarine, MLA and DH beta E. In addition, DMPP
      or lobeline-induced attenuation of basal [3H]ACh release was insensitive to
      blockade by sulpiride, a dopamine (D2) receptor antagonist. In contrast to their
      effects on NMDA-evoked striatal [3H]ACh release, both DMPP and lobeline increased
      basal release of striatal [3H]DA and hippocampal [3H]norepinephrine ([3H]NE) and
      did not attenuate NMDA-evoked release of these two transmitters. Instead, DMPP
      and lobeline appeared to have an additive effect on both NMDA-evoked hippocampal
      [3H]NE release and striatal [3H]DA release. These pharmacological results suggest
      that the inhibitory effects on lobeline and DMPP on striatal [3H]ACh release are
      independent of their interactions with classical NAChRs or the NMDA receptor
      complex itself.

PMID- 9144641
TI  - The pharmacology of the novel and selective sigma ligand, PD 144418.
AB  - The pharmacology of PD 144418 (1-propyl-5-(3-p-tolyl-isoxazol-5-yl)-1,2,3,6
      tetrahydropyridine) was characterized using neurochemical, biochemical and
      behavioral techniques. For sigma (sigma 1 and sigma 2 respectively) sites, PD
      144418 affinities were determined using whole guinea pig brain membranes with
      [3H](+)-pentazocine and neuroblastoma x glioma cell membranes using [3H]1,3,di-O
      tolylguanidine (DTG) in the presence of 200 nM (+)-pentazocine. PD 144418
      exhibited an affinity for sigma 1 of 0.08 nM (Ki) versus a K1 of 1377 nM for
      sigma 2 site. Additional receptor binding studies indicated that PD 144418 lacked
      affinity for dopaminergic, adrenergic, muscarinic and a variety of other
      receptors. In vitro studies indicated that PD 144418 reversed the N-methyl-D
      aspartate (NMDA)-induced increase in cyclic GMP (cGMP) in rat cerebellar slices
      without affecting the basal levels, suggesting that sigma 1 sites may be
      important in the regulation of glutamine-induced actions. PD 144418 potentiated
      the decrease in 5-hydroxytryptophan caused by haloperidol in the mesolimbic
      region, but by itself had no effect in 5-hydroxytrypamine (5-HT) and dopamine
      (DA) synthesis. Behaviorally, similar to other sigma ligands, PD 144418
      antagonized mescaline-induced scratching at doses that did not alter spontaneous
      motor activity. This action is suggestive of potential antipsychotic property. It
      exhibited no anxiolytic and antidepressant properties in the models used. These
      results show that PD 144418 is a very selective sigma 1 agent, devoid of any
      significant affinity for other receptors and that sigma 1 site may modulate
      actions in the CNS.

PMID- 9144642
TI  - Expression of functional GABAA receptors in transfected L929 cells isolated by
      immunomagnetic bead separation.
AB  - Transient cotransfection of fibroblasts, with plasmids encoding individual GABAA
      receptor (GABAAR) subunits, has provided a model to characterize the
      pharmacological and kinetic properties of receptor subtype combinations. However,
      identifying transfected cells for electrophysiological recording is often
      difficult due to low transfection efficiencies. Selection of transfected cells
      has required cotransfection with a marker gene and fluorescence microscopic
      localization prior to recording. To circumvent these problems, two GABAAR
      subtypes combinations in transfected L929 cells were isolated with a novel
      biomagnetic separation system. Cell selection was accomplished by cotransfection
      with a plasmid (pHook-1) encoding a single-stranded cell surface antibody (sFv),
      which bound to ferromagnetic beads, coated with an antigen (phOx). Bead-covered
      cells were then magnetically separated from non-transfected cells. Bead-selected
      cells cotransfected with alpha 6, beta 3 and gamma 2L subtypes, expressed GABAAR
      currents in 95% (41/43) of cells recorded. Cells cotransfected with alpha 5, beta
      3 and gamma 2L subtypes had an EC50 for GABA of 5.4 microM and a Hill slope of
      1.4. Membrane patches from cells expressing the alpha 5 beta 3 gamma 2L isoform
      demonstrated single channel currents with a main conductance state of 23 pS.
      Magnetic bead immunoselection provides a purified population of transfected cells
      well suited for whole cell and single channel recording.

PMID- 9144643
TI  - Beta-adrenergic modulation of GABAergic inhibition in the deep cerebellar nuclei
      of F344 rats.
AB  - The presence of norepinephrine (NE) and NE activated cells, in the deep
      cerebellar nuclei (DCN) of male F344 rats, was investigated using
      immunohistochemistry and electrophysiology, during iontophoresis of the beta
      adrenergic agonist isoproterenol (ISO). During extracellular electrophysiology,
      GABA was iontophoretically applied to the cell and ISO was then co-applied in an
      attempt to modulate the GABAergic inhibition of cell firing in the DCN.
      Immunohistochemistry was used to detect tyrosine hydroxylase (TH) positive fibers
      in the DCN. Isoproterenol modulated GABAergic inhibition in 51% of the DCN cells
      recorded from. In addition, TH-positive fibers that appeared to make contact with
      DCN cells were found. Therefore, this study demonstrated that functional NE
      receptors exist in the DCN and NE appears to be present in fibers therein.

PMID- 9144645
TI  - The neurotensin antagonist SR 48692 fails to modify the behavioural responses to
      a dopamine D1 receptor agonist in the rat.
AB  - The effects of the neurotensin antagonist SR 48692 on the behavioural responses
      to the dopamine D1 receptor agonist SKF 38393 were investigated in the rat. SKF
      38393 (5 mg/kg s.c.) elicited vacuous chewing movements (VCMs) and grooming,
      which were unaffected by SR 48692 (50 micrograms/kg i.p.). The dopamine D2
      receptor antagonist raclopride (0.5 mg/kg s.c.) elicited a small increase in VCMs
      in animals treated with SR 48692 and attenuated grooming induced by SKF 38393.
      These effects were not otherwise modified by SR 48692. We conclude that VCMs
      induced by acute administration of a dopamine D1 receptor agonist are unlikely to
      be dependent upon enhanced release of neurotensin in the striatum or its
      projections. This is contrast to the vacuous chewing response which emerges
      following chronic administration of neuroleptics, which is attenuated by
      neurotensin receptor antagonist. Thus, inasmuch as chronic neuroleptic-induced
      VCMs in the rat may be analogous to tardive dyskinesia in humans, the responses
      induced by acute administration of a D1 agonist to the rat cannot be used as a
      model of this disorder. Furthermore, the behavioural effects of chronic
      neuroleptic administration reflect more than a simple shift in the balance of D1
      versus D2 receptor stimulation.

PMID- 9144644
TI  - The 5-HT1D receptor antagonist GR-127,935 prevents inhibitory effects of
      sumatriptan but not CP-122,288 and 5-CT on neurogenic plasma extravasation within
      guinea pig dura mater.
AB  - The aim of this study was to examine whether GR-127,935, a 5-HT1B/1D receptor
      antagonist, blocks the inhibitory effects of sumatriptan, CP-122,288 and 5
      carboxamidotryptamine (5-CT) on plasma protein extravasation, within guinea pig
      and rat dura matter, following electric stimulation of the trigeminal ganglion.
      Binding studies first established that GR-127,935 shows a 500-fold selectivity
      for 5-HT1D binding sites (labeled by [3H]L-694,247) versus 5-HT1F binding sites
      (labeled by [3H]sumatriptan in the presence of 50 nM 5-carboxamidotryptamine) in
      guinea pig forebrain homogenates (pKD +/- SD = 7.0 +/- 0.2 at 5-HT1F sites and
      9.7 +/- 0.1 at 5-HT1D sites). In guinea pigs, GR-127,935 showed partial agonist
      activity and inhibited dural plasma protein extravasation. Increasing doses of GR
      127,935 reversed the effect of sumatriptan, but did not affect the action of 5-CT
      and CP-122,288 (at a dose as high as 2 mumol/kg). Sumatriptan, CP 122,288 and 5
      CT dose-responsively inhibited plasma protein extravasation. At a dose of 2
      mumol/kg (but not at 0.2 mumol/kg), GR-127,935 right-shifted the dose-response
      curve of sumatriptan. No significant rightward shift was observed in the dose
      response of CP-122,288 and 5-CT. In rats, GR-127,935 did not show any significant
      partial agonist activity. A dose of 0.2 mumol/kg was sufficient to right-shift
      the dose-response curve of sumatriptan. These data suggest that sumatriptan
      inhibits neurogenic inflammation via 5-HT1D alpha receptors in guinea pigs and 5
      HT1D beta (5-HT1B) receptors in rats. Additional receptor subtypes are likely to
      be involved in the inhibition of plasma extravasation by CP-122,288 and 5-CT.
      Pertussis toxin reduced the inhibitory effects of both sumatriptan and 5-CT, but
      not of muscimol, known to act at GABAA receptors. These results suggest that 5
      CT, as well as sumatriptan, act at a receptor linked to an inhibitory G-protein.

PMID- 9144646
TI  - Effects of chronic ethanol treatment and ethanol withdrawal on [3H]SCH23390
      binding to rat striatal membranes.
AB  - The effects of chronic ethanol administration and ethanol withdrawal on the
      kinetic and pharmacological properties of [3H]SCH23390 binding sites and the
      labelling of central dopamine D-1 receptors were studied in the striatum of the
      rat. Chronic 40 day ethanol treatment produced a statistically significant
      decrease (p < 0.05) in maximum binding (Bmax) on striatal dopamine D-1 receptors
      of the rat, KD remaining unaltered. The withdrawal of ethanol did not affect the
      kinetic binding parameters. The rank order of potency in displacing the specific
      [3H]SCH23390 binding of several dopamine antagonists, agonists and serotonin
      related drugs was consistent with the pharmacological profile of dopamine D-1
      receptors. Chronic ethanol treatment led to a statistically significant increase
      in receptor affinity (lower Ki than controls) for (+)-butaclamol (p < 0.05).
      Ethanol withdrawal for 24 hr increased the affinity of [3H]SCH23390-labeled
      binding sites for norepinephrine. The addition of 0.03-0.68 M ethanol in vitro
      had no significant effects on [3H]SCH23390 binding in striatal preparations taken
      from both control and ethanol-treated rats. The results show that rat striatal
      [3H]SCH23390-labelled binding sites are affected by different conditions of
      ethanol exposure, possibly suggesting the medication of striatal dopamine
      pathways in the responses to ethanol intoxication.

PMID- 9144647
TI  - Exploration of P-type Ca2+ channels as drug targets for the treatment of epilepsy
      or ischemic stroke.
AB  - We investigated the neuroprotective efficacy of the P-type Ca2+ channel
      antagonist daurisoline against electroshock-induced convulsions in rats and mice,
      hypoxic/hypoglycemic-induced damage in rat hippocampal slices and brain damage
      induced by occlusion of the middle cerebral artery (MCA) in rats. Daurisoline
      applied intravenously (i.v.) (bolus of 1-60 mg/kg) reduced the spontaneous
      activity of rat cerebellar Purkinje cells in a dose-dependent manner, a result
      demonstrating activity in the brain with systemic administration of the compound.
      While this effect reversed rapidly in about 10-20 min following bolus-application
      of the drug at doses of up to 30 mg/kg, a dose of 60 mg/kg consistently induced a
      depression of respiration followed by death of the animals. Daurisoline
      administered at 10-30 mg/kg did not prevent electroshock-induced convulsions in
      mice or rats, nor did it reduce the neuronal damage in hippocampal slices induced
      by a hypoxic/hypoglycemic insult in vitro by MCA occlusion in vivo. These
      observations do not support the hypothesis that P-type Ca2+ channels are
      promising drug targets for the acute treatment of epileptic convulsions and/or
      ischemic stroke.

PMID- 9144648
TI  - Bradykinin inhibition of N- and L-type calcium channel currents in NG108-15
      cells.
AB  - The bradykinin regulation of calcium channel currents in NG108-15 neuroblastoma x
      glioma hybrid cells was examined, in order to determine: (1) which type of
      bradykinin receptors mediates the inhibition of N-type calcium channels in these
      cells; and (2) whether bradykinin can modulate other types of calcium channels in
      these cells. Bradykinin inhibited both N- and L-type calcium channels in NG108-15
      cells, with EC50S of 10 +/- 2 nM and 29 +/- 7 nM, respectively. The inhibition of
      both L- and N-type calcium channels by bradykinin (100 nM) could be completely
      inhibited by the bradykinin B2 receptor antagonist Hoe 140 (10 nM). Bradykinin
      appeared to inhibit that portion of the L-type calcium channel current that was
      also reversibly inhibited by omega-conotoxin GVIA. The bradykinin inhibition of
      the L-type calcium channel current was partly reduced by pretreatment of the
      cells with pertussis toxin, whereas the inhibition of the N-type current was
      pertussis toxin-insensitive. In some cultures it was observed that the bradykinin
      B1 receptor agonist desArg9bradykinin inhibited the L-type calcium channel
      current.

PMID- 9144649
TI  - delta-opioid receptor mobilization of intracellular calcium in SH-SY5Y cells:
      lack of evidence for delta-receptor subtypes.
AB  - delta-opioid receptor agonists mobilize intracellular Ca2+([Ca2+]i) in SH-SY5Y
      cells when applied in the presence of muscarinic agonists. The putative delta 1
      receptor agonist [D-Pen2,D-Pen5]-enkephalin (DPDPE) elevated [Ca2+]i with an EC50
      of 11 nM and the putative delta 2 agonist deltorphin II elevated [Ca2+]i, with an
      EC50 of 14 nM. The maximal elevations of [Ca2+]i caused by both agonists were not
      different, nor were maximally effective concentrations of DPDPE (1 microM) and
      deltorphin II (1 microM) applied together more effective than either agonist
      applied alone. The elevations of [Ca2+]i caused by DPDPE (1 microM) and
      deltorphin II (1 microM), in the presence of carbachol, desensitized rapidly with
      continued opioid exposure and the cross-desensitization between PDPDE and
      deltorphin II was complete. The putative delta 1 selective antagonist 7
      benzylidenenaltrexone (BNTX) and the putative delta 2 selective antagonist
      naltriben both reduced the elevations of [Ca2+]i caused by DPDPE (30 nM) and
      deltorphin II (10 nM), by greater than 50% at concentrations of less than 10 nM.
      In SH-SY5Y cells delta-receptor mediated elevation of [Ca2+]i is mediated by a
      population of receptors, which does not discriminate between agonists and
      antagonists purportedly selective for delta 1 or delta 2 receptors.

PMID- 9144650
TI  - Impairment of pupillary responses and optokinetic nystagmus in the mGluR6
      deficient mouse.
AB  - Retinal bipolar cells receive glutamatergic transmission from photoreceptors and
      mediate a key process in segregating visual signals into ON-center and OFF-center
      pathways. The segregation of ON responses involves a G protein-coupled
      metabotropic glutamate receptor (mGluR). The mGluR6 subtype is expressed
      restrictedly at the postsynaptic site of retinal ON-bipolar cells. Ablation of
      mGluR6 in the ON-bipolar cells by gene targeting results in a loss of ON
      responses but unchanged OFF responses in visual transmission. Thus, mGluR6 is
      essential for inducing ON responses. The aims of this study are analyses of
      visual responsiveness and possible visual dysfunction in mGluR6-deficient mice.
      We report here that mGluR6-deficient mice have unaltered locomotor activity in a
      daily light-dark cycle and exhibit light-stimulated induction of Fos
      immunoreactivity in the suprachiasmatic nucleus. These findings indicate that
      mGluR6-deficient mice are capable or responding to light stimulation. The mGluR6
      deficiency, however, markedly reduces the sensitivity of pupillary responses to
      light stimulus and severely impairs the ability to drive optokinetic nystagmus in
      response to visual contrasts. This study thus demonstrates that mGluR6
      contributes to discrimination of visual contrasts.

PMID- 9144651
TI  - Cloning, distribution and functional expression of the human mGlu6 metabotropic
      glutamate receptor.
AB  - The cDNA encoding the human metabotropic glutamate receptor type 6 (hmGlu6) was
      isolated from a human retinal cDNA library. The deduced primary sequence (877
      amino acids) of the hmGlu6 receptor was 93.5% identical to its rat counterpart
      and shared 69.8% sequence identity with the related hmGlu4 receptor clone (912
      amino acids), isolated in parallel from a human brain cDNA library. In situ
      hybridization revealed that the hmGlu6 mRNA is highly expressed in cells located
      in the inner nuclear layer of the human retina, presumably bipolar neurons.
      Neither PCR analysis nor in situ hybridization could detect hmGlu6 mRNA in human
      brain. When stably expressed in Chinese hamster ovary cells (CHO-K1) the hmGlu6
      receptor inhibited adenylate cyclase through a pertussis toxin-sensitive G
      protein, and reduced forskolin-elevated cyclic adenosine monophosphate (cAMP)
      levels in response to agonists. The rank order of agonist potency was L(+)-2
      amino-4-phosphonobutyric acid (L-AP4) > L-serine-O-phosphate > L-glutamate >
      quisqualate = (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD).
      (2S,3S,4S)-alpha-(carboxycyclopropyl)-glycine (L-CCG-I) was a partial agonist at
      the hmGlu6 receptor, with a potency approaching that of L-serine-O-phosphate.

PMID- 9144652
TI  - A novel splice variant of a metabotropic glutamate receptor, human mGluR7b.
AB  - Two splice variants of the human metabotropic glutamate receptor 7, named
      hmGluR7a and hmGluR7b, were isolated from a human brain cDNA library. The
      isoforms differ by an out-of-frame insertion of 92 nucleotides close to the C
      terminus of the hmGluR7 coding region, hmGluR7a has a length of 915 amino acids
      and represents the human homolog of the recently cloned rat mGluR7. hmGluR7b is
      seven amino acids longer and exhibits a novel C-terminus of 23 amino acids in
      length. RT-PCR analysis demonstrated the existence of mGluR7b transcripts in wild
      type mouse brain and its absence in mGluR7 knockout mice. Northern blot analysis
      indicate that mGluR7 expression is developmentally regulated. It is expressed at
      high levels in human fetal brain and at a lower level in many regions of adult
      human brain. Stimulation of hmGluR7b with L-2-amino-4-phosphonobutyrate (L-AP4),
      L-serine-O-phosphate (L-SOP) or L-glutamate in stably transfected Chinese hamster
      ovary (CHO) cells depressed forskolin-induced cAMP accumulation, whereas (1S,3R)
      1-aminocyclopentane-1,3,-dicarboxylic acid ((1S,3R)-ACPD) and quisqualate (both
      at 1mM) had no significant effects. As described for rat mGluR7, the rank order
      of agonist potencies is: L-SOP, L-AP4 > L-glutamate > (1S,3R)-ACPD, quisqualate.

PMID- 9144653
TI  - Endogenous adenosine attenuates long-term depression and depotentiation in the
      CA1 region of the rat hippocampus.
AB  - This study tested the hypothesis that endogenous adenosine, a neuromodulator
      which is known to modify long-term potentiation (LTP), might also affect other
      forms of long-lasting synaptic plasticity, namely long-term depression (LTD) and
      depotentiation, in the hippocampus. Long-term depression was induced by applying
      low-frequency stimulation (LFS; 1 Hz, 900 stimuli, test intensity) to the
      Schaffer collateral-commissural fibres in hippocampal slices taken from young (12
      14-day old) animals. Depotentiation was induced by delivering LFS to a pathway in
      which LTP had previously been saturated. Under control conditions, LTD induced in
      two distinct pathways was similar. However, low-frequency stimulation, applied in
      either pathway in the presence of the selective adenosine A1 receptor antagonist,
      1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 10 nM), resulted in LTD which was
      larger than in control conditions. In a similar way, while under control
      conditions depotentiation induced in two distinct pathways was similar, when LFS
      was applied in the presence of DPCPX (10 nM) facilitation of depotentiation was
      observed. These results suggest that endogenous adenosine, acting through
      adenosine A1 receptors, is able to attenuate long-term depression and
      depotentiation in the hippocampus.

PMID- 9144654
TI  - Endogenous adenosine on membrane properties of CA1 neurons in rat hippocampal
      slices during normoxia and hypoxia.
AB  - The effects of endogenous adenosine release on CA1 neurons in hippocampal slices
      were studied under normoxic and hypoxic conditions, by using extra-/intracellular
      and whole-cell recordings. During normoxia, the adenosine antagonist, 8-(p
      sulphophenyl) theophylline (8-SPT) or adenosine deaminase (ADA) potentiated both
      evoked CA1 EPSPs and spontaneous synaptic activity, but not monosynaptic IPSPs;
      there was a minimal depolarization (by 1 mV), probably caused by the enhanced
      synaptic activity, but no increase in input conductance. Under voltage-clamp with
      KCl electrodes (with holding potential (VH) near -70 mV), hypoxia (4-5 min)
      elicited a rise in input conductance and an outward current that reversed near 
      90 mV, in keeping with the activation of K conductance. These effects of hypoxia
      were partly attenuated by 8-SPT (10 microM). The hypoxia-induced outward current
      and conductance increase were abolished by 1 mM Ba, being replaced by a small
      inward current and a conductance decrease. These data indicate that adenosine
      tonically inhibits excitatory, but not inhibitory, synaptic transmission, has no
      direct effect on input conductance, and contributes to the hyperpolarization and
      fall in input resistance induced by hypoxia.

PMID- 9144655
TI  - Mechanisms of hippocampal reoxygenation injury. Treatment with antioxidants.
AB  - The effects of hypoxia of different durations (8, 12 or 15 min) and of subsequent
      reoxygenation were studied in rat hippocampal slices by measuring enzyme
      activities related to oxidative stress: superoxide dismutase (SOD), cytochrome c
      oxidase and lactate dehydrogenase (LDH). Simultaneously the degree of lipid
      peroxidation was estimated by measuring conjugated dienes (CD). Reoxygenation
      after 8-min of hypoxia induced general cell injury indicated by increased LDH
      activity. Reoxygenation after 12-min of hypoxia started lipid peroxidation
      assessed by an increase in CD, and after 15-min of hypoxia followed by
      reoxygenation CD were found to be significantly decreased, suggesting lipid
      degradation. The injury induced by a hypoxia of 12 min and reoxygenation was
      reduced by SOD and catalase, indicating that oxygen radicals were involved in
      this process. The oxygen radicals originating from the xanthine/xanthine oxidase
      system, from the synthesis of prostaglandins, as well as from the mitochondrial
      respiratory chain, since allopurinol, indomethacin and rotenone decreased while
      antimycin increased reoxygenation injury. An increase in ATP may also have been
      involved as cyanide, an inhibitor of ATP synthesis, decreased the reoxygenation
      injury. The chain-breaking antioxidants trolox, alpha tocopherol and the
      pyridoindole stobadine were effective in preventing reoxygenation injury,
      indicating the involvement of lipid peroxidation in this process.

PMID- 9144656
TI  - Polyamine FTX-3.3 and polyamine amide sFTX-3.3 inhibit presynaptic calcium
      currents and acetylcholine release at mouse motor nerve terminals.
AB  - FTX-3.3 is the proposed structure of a calcium-channel blocking toxin that has
      been isolated from the funnel web spider (Agelenopsis aperta). The effects of FTX
      3.3 and one of its analogues, sFTX-3.3, on acetylcholine release, on presynaptic
      currents at mouse motor nerve terminals and on whole-cell sodium currents in
      SK.N.SH cells (a human neuroblastoma cell line) have been studied. FTX-3.3 (10-30
      microM) and sFTX-3.3 (100-300 microM) reversibly reduced release of acetylcholine
      by approximately 70-90% and 40-60%, respectively. FTX-3.3 (10 microM) blocked the
      fast component of presynaptic calcium currents by approximately 60%. sFTX-3.3
      (100 microM) reduced the duration of the slow component of presynaptic calcium
      currents by about 50% of the control and also reduced presynaptic sodium current
      by approximately 20% of the control. sFTX-3.3 (100 microM) reduced whole-cell
      sodium current recorded from SK.N.SH cells by approximately 15%, whereas FTX-3.3,
      even at 200 microM, did not affect this current. Since the only difference in
      chemical structures of these toxins is that sFTX-3.3 has an amide function which
      is absent in FTX-3.3, the amide function may be responsible for the reduced
      potency and selectivity of sFTX-3.3. This study also provides further support for
      the existence of P-type calcium channels at mouse motor nerve terminals.

PMID- 9144657
TI  - Inhibition of neuronal high voltage-activated calcium channels by insect
      peptides: a comparison with the actions of omega-conotoxin GVIA.
AB  - The whole cell variant of the patch clamp technique was used to investigate the
      actions of two novel insect peptides on high voltage-activated Ca2+ currents in
      cultured dorsal root ganglion (DRG) neurones. The insect peptides (PMP-D2 and PMP
      C) were isolated originally from insect brains and fat bodies, and have been
      found to have similar three-dimensional structures to the N-type Ca2+ channel
      inhibitor omega-conotoxin GVIA (omega-CgTx GVIA). High voltage-activated Ca2+
      currents were activated from a holding potential of -90 mV by depolarizing step
      commands to 0 mV. Extracellular application of synthetic PMP-D2 or PMP-C (1
      microM) attenuated high voltage-activated Ca2+ currents. The effects of PMP-C
      were strongly dependent on the frequency of current activation, but inhibition
      was apparent and reached a steady state after 20 steps when currents were evoked
      for 30 msec at 0.1 Hz. The actions of the two insect peptides overlapped both
      with each other and with omega-CgTx GVIA, suggesting that N-type Ca2+ current was
      predominantly sensitive to these peptides. Low voltage-activated T-type current
      and 1,4-dihydropyridine sensitive L-type Ca2+ currents were insensitive to 1
      microM PMP-D2 and PMP-C, which indicates a degree of selectivity. The presence of
      a fucose group on PMP-C abolished the ability of this peptide to attenuate high
      voltage-activated Ca2+ currents, which may reflect a mechanism by which peptide
      function could be regulated in insects. The electrophysiological data are
      supported by studies on 45Ca2+ influx into rat cerebrocortical synaptosomes. Both
      PMP-D2 (10 microM), PMP-C (10 microM) and omega-CgTx GVIA (1 microM) attenuated a
      proportion of 45Ca2+ influx into the synaptosomes, but additive effects of these
      peptides were not observed. We conclude that these naturally occurring peptides
      obtained from invertebrate preparations have inhibitory effects on N-type Ca2+
      channels. Although the peptides have related three-dimensional structures, they
      have distinct amino acid sequences and appear to have different mechanisms of
      action to produce inhibition of mammalian neuronal high voltage-activated Ca2+
      channels.

PMID- 9144658
TI  - Dual modulation of an inwardly rectifying potassium conductance.
AB  - The modulation of a constitutively active IRK1-like inwardly rectifying potassium
      channel, that is endogenously expressed in the RBL-2H3 cell, was studied with the
      whole-cell patch-clamp technique. Activation of G-proteins by intracellular
      application of GTP gamma S revealed a dual modulation of the inward rectifier. An
      initial increase in inward current amplitude was induced by GTP gamma S, followed
      by a profound inhibition of the current. The stimulation of the inward rectifier
      by GTP gamma S was abolished by pretreatment with pertussis toxin. The inhibitory
      phase of the GTP gamma S-induced response was pertussis toxin-insensitive.
      Stimulation of the m1-muscarinic receptor expressed in the RBL cell after stable
      transfection, induced an inhibition of the inwardly rectifying currents.
      Application of protein kinase C activators such as phorbol 12-myristate 13
      acetate and phorbol 12,13-dibutyrate, resulted in a strong inhibition of the
      currents. Application of the cAMP-dependent protein kinase activator 8-bromo cAMP
      also induced an inhibition of the inward rectifier. It is concluded that the
      inward rectifier of the RBL-2H3 cell may be inhibited both by activation of
      protein kinase C and by cAMP-dependent protein kinase. As this type of inward
      rectifier is widely expressed in the nervous system, these data imply that the
      channel can be inhibited by receptors that stimulate phospholipase C and/or
      stimulate adenylyl cyclase, and can be activated by receptors that inhibit
      adenylyl cyclase activity.

PMID- 9144659
TI  - Postnatal expression of melanocortin-3 receptor in rat diencephalon and
      mesencephalon.
AB  - In situ hybridization was applied to examine the postnatal expression of
      melanocortin-3 (MC-3) receptor mRNA in the rat brain. Very weak and limited
      signals were seen in the hypothalamus on postnatal day 0 (P0) and in the dorsal
      lateral thalamus on P4. A marked increase was noted in several regions of the
      diencephalon and mesencephalon on P7. The highest levels were reached on P21,
      which was the time when an adult-like pattern was established. On P21, intense
      signals were seen in the ventromedial nucleus and the arcuate nucleus of the
      tuberal hypothalamus, the habenular nucleus of the epithalamus and the ventral
      tegmental area. [125I] Nle4, D-Phe7-alpha-MSH showed overlapping, but wider
      labelling of melanocortin receptors, that followed a similar developmental
      course. alpha-MSH-like immunoreactivity was seen widely in the forebrain and
      midbrain from P14. In contrast to the staining of alpha-MSH in neurons and their
      process, gamma 2-MSH-like immunoreactivity was detected strongly in the blood
      vessels. The neuronal localization of MC-3 receptor mRNA suggests that this
      receptor may mediate the neurotropic actions of melanocortin peptides in the
      developing brain.

PMID- 9144661
TI  - BW 723C86, a 5-HT2B receptor agonist, causes hyperphagia and reduced grooming in
      rats.
AB  - The 5-HT2B receptor agonist, BW 723C86 (10 and 20 mg/kg s.c.), increased the time
      spent in feeding behaviour of freely-fed rats in observation cages over 15 min.
      BW 723C86 (20 and 50 mg/kg s.c. 30 min pre-test) also modestly increased food
      consumption of freely-fed rats over 1 and 2 hr, but not 4 hr, in their home
      cages. This action was at least partly mediated centrally, as it was reproduced
      by i.c.v. infusion of 1 and 10 micrograms in freely-fed rats. The effect is also
      likely to be 5-HT2B receptor-mediated, as no hyperphagic response to BW 723C86
      (20 mg/kg s.c. 30 min pre-test) was observed in freely-fed rats pretreated with
      the 5-HT2C/2B receptor antagonist SB 206553 (1, 3, 20 or 40 mg/kg p.o. 1 hr pre
      test) while the selective 5-HT1A receptor antagonist, WAY 100635 (0.1 or 0.3
      mg/kg s.c. 30 min pre-test), had no effect. Systemic (1, 10 and 20 mg/kg s.c. 30
      min pre-test) but not i.c.v. (1-30 micrograms) BW 723C86 also reduced the
      frequency of grooming bouts of rats in observation cages. BW 723C86 given either
      s.c. (1-20 mg/kg 30 min pre-test) or i.c.v. (1-30 micrograms) did not cause
      hypolocomotion, penile erection, oral dyskinesias or hyperthermia, behaviours
      associated with administration of the 5-HT2C/2B receptor agonist m
      chlorophenylpiperazine (mCPP), and are thus likely to involve-5-HT2C receptor
      activation.

PMID- 9144660
TI  - Acetaldehyde-induced changes in monoamine and amino acid extracellular
      microdialysate content of the nucleus accumbens.
AB  - The effect of an acute intraperitoneal (i.p.) injection of acetaldehyde, 20 mg/kg
      or 100 mg/kg, on the microdialysate content of both amino acids and monoamines
      was studies in the nucleus accumbens (NA) by a microdialysis technique.
      Acetaldehyde, ACH, which was detectable at levels of 50-130 mumol/g brain tissue
      10 min after injection, evoked a significant decrease in the extracellular
      microdialysis dopamine content, which was sustained for the period of the study,
      i.e. 120 min. Homovanillic acid, HVA, decreased significantly when the lower dose
      of ACH was administered while dihydrophenylacetic acid, DOPAC, showed no
      significant change with either dose of ACH during the period of the study.
      Serotonin levels decreased significantly after both doses of acetaldehyde, with
      significant increases of its major metabolite, hydroxyindolacetic acid, 5-HIAA,
      with the higher acetaldehyde dose. Taurine increased significantly, only during
      the first twenty minutes, after both doses of acetaldehyde, although neither of
      the excitatory amino acids assayed, glutamate and aspartate, nor the inhibitory
      amino acid, GABA, showed any significant changes. Acetaldehyde clearly evokes
      significant perturbation in the monoamine content of the NA, such changes being
      the converse to those reported for monoamines after ethanol administration, which
      might indicate a negative reinforcement effect.

PMID- 9144662
TI  - Competitive and glycine/NMDA receptor antagonists attenuate withdrawal-induced
      behaviours and increased hippocampal acetylcholine efflux in morphine-dependent
      rats.
AB  - The present study has examined the glycine/N-methyl-D-aspartate (NMDA) receptor
      antagonist, R-(+)-3-amino-1-hydroxypyrrolid-2-one (R-(+)-HA-966) and the
      competitive NMDA receptor antagonist, cis-4-(phosphonomethyl)piperidine-2
      carboxylic acid (CGS 19755) on the behavioural syndrome and increased
      hipppocampal acetylcholine efflux induced during morphine-withdrawal in the rat.
      Subcutaneous naltrexone (1 mg/kg) injection, 48 hr after implantation of a 75 mg
      morphine pellet, induced a robust withdrawal syndrome consisting of wet dog
      shakes, ejaculations, mouth movement, ptosis, irritability to touch and
      diarrhoea. Pretreatment with the alpha2-adrenoceptor agonist, clonidine (0.1-0.4
      mg/kg), R-(+)-HA-966 (10-60 mg/kg) or CGS 19755 (5 or 10 mg/kg) significantly
      reduced the incidence of withdrawal behaviours. In addition, all three compounds
      significantly attenuated the increase in hippocampal acetylcholine efflux induced
      following naltrexone (1 mg/kg, s.c.) injection in morphine-dependent rats. These
      results provide further evidence demonstrating that NMDA receptor antagonists
      attenuate both the behavioural and neurochemical effects observed during morphine
      withdrawal in the rat.

PMID- 9144663
TI  - Effect of differential rearing environments on morphine-induced behaviors, opioid
      receptors and dopamine synthesis.
AB  - Rats were raised from weaning (21 days old) to young adulthood (50-60 days old)
      in either an enriched or impoverished stimulus environment. In the enriched
      condition (EC), rats were group-housed with various novel objects that were re
      arranged daily. In the impoverished condition (IC), rats were housed individually
      without any objects. As adults, a four-trial conditioned place preference (CPP)
      test was used to assess locomotor activity and reward produced by morphine (0,
      0.1, 1 or 10 mg/kg). On morphine conditioning day 1, both EC and IC rats
      displayed an inverted U-shaped dose-effect curve for locomotor activity and the
      locomotor stimulant effect of acute morphine was greater in IC than EC rats.
      Across morphine conditioning days 1-4, both EC and IC rats displayed locomotor
      sensitization; the locomotor sensitization following repeated morphine injections
      was greater in IC than EC rats. In contrast to the enhanced locomotor stimulant
      effect of morphine observed in IC rats, morphine-induced CPP was attenuated in IC
      rats relative to EC rats, indicating that the locomotor and rewarding effects of
      opioids depend upon different neural substrates. Measurement of mu opioid
      receptor density and rates of morphine-stimulated dopamine synthesis in the
      mesolimbic and nigrostriatal systems of EC and IC rats revealed no reliable
      differences between groups. Therefore, the ability of mu opioid receptors to
      modulate mesolimbic dopamine neurotransmission does not account for the
      differential behavioral effects of morphine in EC and IC rats.

PMID- 9144664
TI  - Activation of phospholipases C and D by the novel metabotropic glutamate receptor
      agonist tADA.
AB  - In hippocampal slices taken from 8-day-old rats, trans-azetidine-2,4-dicarboxylic
      acid (tADA), a novel glutamatergic agonist acting preferentially at class I mGluR
      receptors, activates phosphoinositide and phosphatidylcholine hydrolysis with
      widely different potencies. Inositol phosphate formation was maximally increased
      at 10 microM tADA (EC50: 1.2 microM), while phospholipase D activation was
      observed at a tADA concentration of 1 mM. This is the first report of a tADA
      induced phospholipase D activity.

PMID- 9144665
TI  - (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) activates mGlu5, but no mGlu1,
      receptors expressed in CHO cells and potentiates NMDA responses in the
      hippocampus.
AB  - A new phenylglycine derivative, (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), has
      been synthesized and shown to selectively activate mGlu5a receptors, compared to
      mGlu1 alpha receptors, when expressed in CHO cells. This selective mGlu5 receptor
      agonist also potentiates NMDA-induced depolarizations in rat hippocampal slices.
      CHPG may be a useful tool for studying the role of mGlu5 receptors in the central
      nervous system.

PMID- 9144666
TI  - A brief history of Russian aphasiology.
AB  - This paper analyzes early Russian contributions to the study of aphasia, dated
      between 1789 and 1941. Different approaches to the problem of the organization
      and localization of verbal functions as well as to the understanding of
      mechanisms of aphasia and principles of aphasia rehabilitation are discussed.
      Comparisons with European and North American contributions and with contributions
      from later Russian writing (e.g., Luria's period) are presented to demonstrate
      their interconnections in shaping the course of Russian aphasiology.

PMID- 9144667
TI  - An attempt towards differentiating attentional deficits in traumatic brain
      injury.
AB  - Attentional deficits in patients suffering traumatic brain injury (TBI) can occur
      with minor to severe impact to the brain. Based on reviews of both the cognitive
      and neurobehavioral literature, the following three concepts of attention are
      addressed: (a) arousal/alertness, (b) selective attention, and (c) energetic
      aspects of attention, which include such components as effort, resource
      allocation, and speed of processing. Within each concept, definitions are
      proposed, the underlying brain mechanisms are identified, and the specific
      deficits associated with TBI are explored. This review combines theoretical
      perspectives and clinical findings with the objective of leading toward a
      diagnostic differentiation that in turn will benefit treatment planning.

PMID- 9144669
TI  - MRI of head injury using FLAIR.
AB  - We studied the utility of fluid-attenuated inversion-recovery (FLAIR) MRI in the
      investigation of head injury. We examined 56 patients with head injuries with T2
      weighted spin-echo (SE) and FLAIR sequences. In all cases, the sensitivity of
      FLAIR images to equal or superior to that of conventional SE images to the
      traumatic lesions. In 9 cases, central diffuse axonal injury of the fornix and
      corpus callosum could be seen only on sagittal FLAIR images.

PMID- 9144668
TI  - Neurocognitive functioning in chronic fatigue syndrome.
AB  - Although substantial research has been conducted on chronic fatigue syndrome
      (CFS) over the past decade, the syndrome remains poorly understood. The most
      recent case definition describes CFS as being characterized both by disabling
      fatigue and by subjective reports of difficulty with concentration and "short
      term" memory. However, research into the neurocognitive and psychological
      functioning of individuals with CFS has provided mixed objective results. The
      current paper reviews studies that have examined the neurocognitive and/or
      psychological functioning of individuals with CFS. Changes in research design and
      instruments employed to study individuals with CFS are suggested.

PMID- 9144670
TI  - Fast FLAIR of the brain: the range of appearances in normal subjects and its
      application to quantification of white-matter disease.
AB  - Axial fast FLAIR images of the brains of 40 normal volunteers in four age groups
      between 16 and 55 years were examined and the number and size of areas of
      increased white-matter signal recorded. Increased signal in the corticospinal
      tract region was seen at the level of the internal capsule in all subjects,
      extending up towards the centrum semiovale and down towards the pons for 0.5-5.5
      cm (median 2.5 cm). In all cases the IIIrd and IVth ventricles were outlined by a
      thin line of high signal. Focal areas of high signal (caps) were seen around the
      frontal and occipital horns in 90% and 77% respectively; 54% of caps were
      asymmetrical. None of the above features varied with the age or sex of the
      subject, but the numbers of discrete white matter 'lesions' increased with age.
      The findings are used to suggest guidelines for the identification of areas of
      'normal' high signal to be excluded in quantification of lesions on fast FLAIR
      images.

PMID- 9144671
TI  - Dynamic contrast-enhanced T2*-weighted MRI in patients with cerebrovascular
      disease.
AB  - Our purpose was to investigate the potential of dynamic susceptibility contrast
      enhanced MRI in assessing regional haemodynamics in patients with cerebrovascular
      disease. T2*-weighted FLASH sequences were performed on a control group of 10
      healthy subjects, 13 patients with unilateral stenosis or occlusion of the
      internal carotid artery and 6 patients with acute onset of neurological symptoms,
      the observed signal intensities being converted into concentration-time curves. A
      gamma-variate function was fitted to the measured concentration-time curves to
      eliminate effects of tracer recirculation. In each patient the two cerebral
      hemispheres were compared and the difference between the mean transit times and
      the percental change of the regional cerebral blood volume, calculated for each
      side. Patients with haemodynamically significant unilateral carotid obstruction
      can be divided into two subgroups: those with good and those with poor collateral
      supply. Patients with good collateral supply had a slight but not statistically
      significant increase in mean transit time and cerebral blood volume on the
      diseased side, whereas those with poor collaterals had a significant increase
      compared with the control group. In patients with acute onset of neurological
      symptoms perfusion maps clearly demonstrated the disturbed perfusion at a time
      when T2-weighted images were still normal. Perfusion imaging is a reliable and
      noninvasive method of assessing changes in cerebral perfusion in patients with
      unilateral carotid stenosis. This MR technique permits monitoring of haemodynamic
      changes during therapy and thus may become an alternative to SPECT and PET
      scanning. In patients with acute occlusion of a cerebral artery, perfusion
      imaging reveals the entire, perfusion deficit before conventional MRI and thus
      allows early intervention.

PMID- 9144672
TI  - Cerebrospinal fluid pulsation amplitude and its quantitative relationship to
      cerebral blood flow pulsations: a phase-contrast MR flow imaging study.
AB  - Our purpose in this investigation was to explain the heterogeneity in the
      cerebrospinal fluid (CSF) flow pulsation amplitudes. To this end, we determined
      the contributions of the cerebral arterial and jugular venous flow pulsations to
      the amplitude of the CSF pulsation. We examined 21 healthy subjects by cine phase
      contrast MRI at the C2-3 disc level to demonstrate the CSF and vascular flows as
      waveforms. Multiple regression analysis was performed to calculate the
      contributions of (a) the arterial and venous waveform amplitudes and (b) the
      delay between the maximum systolic slopes of the arterial and venous waveforms
      (AV delay), in order to predict the amplitude of the CSF waveform. The
      contribution of the arterial waveform amplitude was positive (r = 0.61; p =
      0.003) to the CSF waveform amplitude and that of the venous waveform amplitude
      was negative (r = -0.50; p = 0.006). Both in combination accounted for 56% of the
      variance in predicting the CSF waveform amplitude (p < 0.0006). The contribution
      of AV delay was not significant. The results show that the variance in the CSF
      flow pulsation amplitudes can be explained by concurrent evaluation of the CSF
      and vascular flows. Improvement in the techniques, and controlled experiments,
      may allow use of CSF flow pulsation amplitudes for clinical applications in the
      non-invasive assessment of intracranial dynamics by MRI.

PMID- 9144674
TI  - Central neurocytoma arising in the third ventricle.

PMID- 9144673
TI  - Foramen of Monro mass: MRI appearances permit diagnosis of cavernous haemangioma.
AB  - Cavernous haemangiomas are most commonly found in the subcortical white matter,
      the pons and the external capsule. We present a case of a cavernous haemangioma
      that appeared as an intraventricular mass at the foramen of Monro. Despite the
      unusual location the diagnosis was established by MRI because of the typical
      appearance. The differential diagnosis included primary and secondary neoplasms
      at the foramen of Monro.

PMID- 9144675
TI  - A case of meningioma with exceptionally extensive oedema.
AB  - We report a meningioma with very extensive surrounding oedema. This finding,
      along with the age of the patient and other clinical features, made correct
      diagnosis difficult. The pathophysiology of oedema in general and its exceptional
      extent in this case are discussed.

PMID- 9144676
TI  - Giant lumbar meningioma: a common tumour in an unusual location.
AB  - We report a 27-year-old woman with atypical sciatica due to a giant, rapidly
      growing, lumbar (T12-S1) meningioma. The unique features of this case are
      discussed and the importance of early investigation by MRI of patients with
      atypical low back pain and sciatica is highlighted.

PMID- 9144677
TI  - An atypical infectious complication of anterior cervical surgery.
AB  - We report a 44-year-old woman who developed an atypical retro-oesophageal abscess
      4 years after anterior cervical surgery with fusion (ACSF). She presented with
      dysphagia but no fever or definite laboratory signs of inflammation. Delayed or
      chronic dysphagia following Cloward's operation is usually related to graft
      displacement. Infection may also, more rarely, be encountered in conjunction with
      dysphagia, but is typically associated with a classical clinical presentation and
      laboratory results. We recommend that in cases of delayed dysphagia without
      evidence of graft migration, the possibility of retropharyngeal infection should
      be considered, even in the absence of clinical signs or supporting laboratory
      evidence. MRI in this rare delayed complication is nonspecific but suggestive,
      and hence represents the imaging modality of choice in such situations.

PMID- 9144678
TI  - Side effects and complications of automated percutaneous lumbar nucleotomy.
AB  - We reviewed the records of 243 patients treated at 271 disc levels to determine
      the incidence of side effects and complications of percutaneous nucleotomy. In
      our early experience there were 7 technical failures (2.5% of all attempts), of
      which 6 were at the 5th disc level. The success rate dropped from 67% at 3 months
      to 60% 1 year after treatment due to recurrences in 16 patients (6.6%). Extruded
      or sequestered fragments were found in 6 patients (2.4%), and may have been
      caused by nucleotomy. However, only one was accompanied by aggravation of
      symptoms. Discitis was seen in 2 patients (0.8%), both treated at two separate
      disc levels. About half the patients experienced increased low back pain, mean
      duration 9 days, after treatment, and 3 (1.2%), of whom 2 also had nonorganic
      disorders, needed admission to hospital because of severe pain. Mild spasm and a
      sensation of instability were noted by 9.6% and 25% of the patients respectively.
      Injury to nerves, bowels, vessels or ureters or a dural leak never occurred. The
      study confirms earlier reports that the rate of serious complications is low.

PMID- 9144679
TI  - The Doppler guide wire: clinical applications in neuroendovascular treatment.
AB  - The application of Doppler-tipped guide wires to measure blood flow velocity in
      coronary and peripheral arteries has been described previously as a valuable
      means of functional assessment in interventional cardiological procedures. In
      animal studies intravascular Doppler has been used in the cerebrovascular system,
      and this appears to be an important field of application for this new technique.
      We used intravascular haemodynamic monitoring by the Doppler guide wire during
      neuroendovascular procedures in patients with different cerebrovascular diseases
      and evaluated the clinical feasibility of the method. We found it a safe
      technique which complements morphological angiographic information with valuable
      functional data. Further studies may be expected to demonstrate the relation of
      flow parameters to clinical outcome.

PMID- 9144680
TI  - Asymmetrical or heterogeneous enhancement of the internal jugular veins in
      contrast-enhanced CT of the head and neck.
AB  - With faster CT scanners, asymmetric/heterogeneous enhancement (ASHE) of the
      internal jugular veins (IJVs) is frequently encountered in the absence of
      pathology. We investigated the frequency, side, pattern and significance of ASHE
      in 200 patients with various head and neck lesions. Non-ionic contrast medium
      (300 mgI/ml) was infused into a forearm vein (right, n = 100); left, n = 100).
      Forty seconds after contrast medium injection, contiguous 5-mm-thick sections
      were obtained craniocaudally from the skull base to the aortic arch. CT machines
      with two different scanning cycle times (3 s, n = 100; 2 s, n = 100) were used.
      ASHE of the IJVs was observed in 51 patients (25.5%); the patient group receiving
      a right-sided injection with a 2-s scan cycle machine, showing a higher frequency
      (44%). ASHE was divided into four patterns: homogeneous low density, focal low
      density, heterogenous opacification and fluid-fluid level formation. ASHE was
      frequently observed in routine contrast-enhanced CT of the head and neck.
      Frequency of ASHE increased when the scanning cycle was shorter. We should be
      aware of this phenomenon to avoid its misinterpretation as venous thrombosis or
      other pathology.

PMID- 9144681
TI  - MRI of mesenchymal chondrosarcoma of the orbit: case report and review of the
      literature.
AB  - Extraskeletal mesenchymal chondrosarcoma is a relatively uncommon entity, an
      orbital location being extremely rare. A review of the literature revealed 16
      reported cases of primary orbital mesenchymal chondrosarcoma demonstrated by
      plain film and CT. To the best of our knowledge, the MRI features of orbital
      extraskeletal mesenchymal chondrosarcoma have not been previously reported. We
      present the case of an 18-year-old man with a 2-year history of progressive
      proptosis of the right eye who underwent CT, dynamic CT, MRI without and with
      gadolinium enhancement, and magnetic resonance angiography of the orbits. CT of
      orbital mesenchymal chondrosarcoma demonstrates a well-defined mass with multiple
      areas of fine and coarse calcification and shows moderate contrast enhancement.
      The noncalcified portions of the mass demonstrate signal intensity lower than or
      equal to gray matter on T1-weighted images and are isointense to the gray matter
      on T2-weighted images. Dynamic CT reveals delayed contrast enhancement. MRI has
      proven to be a valuable diagnostic tool in the diagnosis and differentiation of
      well-defined intraorbital masses. By a combination of CT and MRI, it appears
      mesenchymal chondrosarcoma can be differentiated from other intraorbital lesions,
      such as cavernous hemangioma, hemangiopericytoma, orbital amyloidosis and fibrous
      histiocytoma.

PMID- 9144682
TI  - Dysgenesis of the corpus callosum and associated telencephalic anomalies: MRI.
AB  - We analysed the MRI findings in 23 patients with callosal dysgenesis in relation
      to their associated telencephalic anomalies to investigate the morphological
      significance of the development of Probst's bundles and the anterior commissure
      in congenital callosal dysgenesis. We classified callosal dysgenesis into three
      types: total defect (9 patients), partial defect (7) and hypoplasia (7).
      Associated anomalies were observed in 15 patients, including migration disorder
      (8 patients), micrencephaly (5), and lipoma (2). The remaining 8 patients had no
      associated anomalies. Probst's bundles were not identified in 4 patients with a
      severe migration disorder. An absent or hypoplastic anterior commissure was
      observed in 9 of the 16 patients with callosal defect and all 7 of those with
      callosal hypoplasia. Colpocephaly and keyhole dilatation of the temporal horns
      were seen in 16 and 21 patients, respectively. Callosal dysgenesis may occur not
      only through a defect in the callosal anlage, but also from impaired growth of
      axonal fibres projecting from the cerebral isocortex. Therefore, associated
      telencephalic anomalies may be responsible for additional features in callosal
      dysgenesis. Consequently, identification of Probst's bundles and the anterior
      commissure may be important when assessing cortical development in patients with
      callosal dysgenesis.

PMID- 9144683
TI  - Cisplatin/etoposide vs paclitaxel/cisplatin/G-CSF vs paclitaxel/cisplatin in non
      small-cell lung cancer.
AB  - A phase III trial conducted by Eastern Cooperative Oncology Group (ECOG)
      investigators assessed the possible impact of paclitaxel on survival, response,
      and toxicity in patients with advanced non-small-cell lung cancer. Three regimens
      were compared: cisplatin/etoposide, paclitaxel/ cisplatin/granulocyte colony
      stimulating factor (G-CSF), and paclitaxel/ cisplatin. Patients were randomly
      assigned to the regimens, each of which was repeated every 21 days over a 17
      month period. Response rates were 12% in the cisplatin/etoposide group, 31% in
      the paclitaxel/cisplatin/G-CSF group, and 26% in the paclitaxel/cisplatin group.
      Significant differences in response were observed between the cisplatin/etoposide
      and paclitaxel/cisplatin/G-CSF groups and the cisplatin/etoposide and
      paclitaxel/cisplatin groups; there was no significant difference between patients
      treated with paclitaxel/cisplatin vs paclitaxel/cisplatin/G-CSF. Both paclitaxel
      regimens were associated with significantly higher response rates compared with
      etoposide/cisplatin. Based on preliminary survival analyses, the investigators
      concluded that the paclitaxel regimens may be associated with superior survival.

PMID- 9144684
TI  - Cisplatin/paclitaxel vs cisplatin/teniposide for advanced non-small-cell lung
      cancer. The EORTC Lung Cancer Cooperative Group. The European Organization for
      Research and Treatment of Cancer.
AB  - A total of 332 patients with advanced non-small-cell lung cancer were randomized
      by the European Organization for Research and Treatment of Cancer Lung Cancer
      Cooperative Group (EORTC) to receive one of two cisplatin (Platinol)-based
      chemotherapy regimens: Paclitaxel (Taxol) 175 mg/m2 given by 3-hour infusion
      followed by cisplatin 80 mg/m2 on day 1; Or cisplatin 80 mg/m2 on day 1, followed
      by teniposide (Vumon) 100 mg/m2 given on days 1, 3, and 5. Cycles were repeated
      every 3 weeks. Preliminary analysis of the results of this phase III trial shows
      that hematologic toxicity was decidedly more severe in the group treated with
      cisplatin/teniposide than in those given paclitaxel/cisplatin. Of 264 patients
      evaluable so far, responses have been observed in 47% of those given paclitaxel
      and in 29% of those treated with teniposide. However, extramural radiologic
      response evaluation is still under way, so these figures are expected to change
      somewhat. It appears clear that the paclitaxel-based therapy affords a benefit in
      terms of response and toxicity, but survival results are premature and any
      definite conclusions await final analysis.

PMID- 9144685
TI  - Sequential dose-dense adjuvant therapy with doxorubicin, paclitaxel, and
      cyclophosphamide.
AB  - The recognition of paclitaxel's (Taxol) activity and non-cross-resistance with
      doxorubicin (Adriamycin) in the treatment of metastatic breast cancer has
      motivated study of the agent in the adjuvant setting. However, the ideal means of
      incorporating this new agent is not yet known. In stage IV disease, exciting
      results have been seen with combinations of doxorubicin plus paclitaxel, and this
      approach is being tested as adjuvant treatment. An alternative approach that has
      produced superior results with other non-cross-resistant regimens is sequential
      administration of the combination agents. Based on prior clinical trials, we
      tested sequential dose-dense therapy with high-dose doxorubicin, followed first
      by paclitaxel and then by cyclophosphamide (Cytoxan) for high-risk operable
      breast cancer. This regimen was associated with marked toxicity but was
      nonetheless tolerable and resulted in promising relapse-free survival. This
      regimen is now being compared to high-dose chemotherapy with autologous stem cell
      support for women with operable breast cancer, metastatic to four to nine
      axillary lymph nodes.

PMID- 9144686
TI  - Paclitaxel as first-line treatment for metastatic breast cancer. The Taxol
      Investigational Trials Group, Australia and New Zealand.
AB  - When administered as a single agent in pretreated patients with advanced breast
      cancer, paclitaxel (Taxol) exhibits remarkable antitumor activity. This trial was
      undertaken to compare paclitaxel with standard chemotherapy as front-line therapy
      for this disease. Patients with measurable or evaluable metastatic breast cancer,
      no prior chemotherapy for metastatic disease, and an Eastern Cooperative Oncology
      Group performance status of 0 to 2 were randomized to receive paclitaxel 200
      mg/m2 intravenously over 3 hours for eight cycles (6 months) or standard
      treatment with oral cyclophosphamide (Cytoxan) 100 mg/m2/d days 1 through 14,
      intravenous methotrexate 40 mg/ m2 days 1 and 8, intravenous 5-fluorouracil 600
      mg/m2 days 1 and 8, and oral prednisolone 40 mg/m2/d (CMFP) days 1 through 14 for
      six cycles (6 months). Patients whose disease progressed or relapsed were
      recommended to receive second-line epirubicin. Accrual has been completed with
      208 patients randomized, but a preplanned interim analysis of the first 100
      patients is reported here. Analysis of quality of life, assessed by a linear
      analogue scale and overall quality of life indices, is ongoing. Objective
      response occurred in 31% (confidence interval, 19% to 45%) with paclitaxel and
      35% (confidence interval, 22% to 51%) with CMFP with stable disease in an
      additional 33% and 29%, respectively. Median time to progression was 5.5 months
      for paclitaxel-treated patients and 6.4 months for those given CMFP, with median
      survival durations of 17.3 and 11.3 months, respectively. Grades 3 and 4
      neutropenia occurred in 64% of patients treated with paclitaxel and in 63%
      treated with CMFP. However, febrile neutropenia was the primary reason for
      hospitalization in 1% of paclitaxel courses, compared with 8% of CMFP courses.
      Nine percent of the patients had major infections with CMFP, but none were seen
      with paclitaxel. Moderate or severe mucositis occurred in 13% of paclitaxel
      treated and 27% of CMFP-treated patients. Alopecia and peripheral neuropathy were
      more common with paclitaxel. Quality of life assessments in the first 100
      patients suggest better overall results on paclitaxel treatment as compared with
      CMFP. Preliminary analyses suggest that single-agent paclitaxel is well tolerated
      and provides comparable control of metastatic cancer to CMFP combination therapy
      when used as front-line treatment.

PMID- 9144687
TI  - A phase II study of doxorubicin/paclitaxel plus G-CSF for metastatic breast
      cancer.
AB  - This phase II trial was conducted to evaluate the percentage of objective
      responses and the toxicity profile of combination doxorubicin (Adriamycin) and
      paclitaxel (Taxol) with granulocyte colony-stimulating factor as first-line
      therapy for patients with metastatic breast cancer (MBC) not previously exposed
      to anthracycline-containing regimens. Patients with measurable, visceral-dominant
      MBC and a performance status of 0 to 2 were included in the study. Doxorubicin 60
      mg/m2 was administered as a short intravenous infusion, followed by paclitaxel
      250 mg/m2 as a 3-hour intravenous infusion on day 1. Granulocyte colony
      stimulating factor 5 micrograms/kg/d was given prophylactically as a subcutaneous
      injection from day 2 until granulocyte recovery to > or = 1,500/mm3. Treatment
      was repeated every 21 days for a maximum of six courses. Dose reductions (to
      doxorubicin 50 mg/m2 and paclitaxel 175 mg/m2) and/or treatment delay were
      applied in case of severe toxicity. All 25 women who entered were evaluable for
      response and toxicity. The main grade 3/4 toxicities observed were leukopenia,
      thrombocytopenia, and mucositis. Alopecia occurred in all patients. No clinically
      relevant cardiovascular toxicity was observed. Severe myelosuppression and/or
      mucositis necessitated dose reductions at courses 2 or 3 in all but one patient.
      The complete response rate was 28%, and the partial response rate was 52% for an
      overall objective response rate of 80%. Median progression-free survival for
      complete responders was 11 months (range, 3 to 24 months), while the progression
      free survival was 7+ months (range 2 to 14+ months) for partial responders and 5
      months (range, 3 to 9 months) for nonresponders. This combination produces a high
      objective response rate in women with MBC, but dose reductions were necessary in
      almost all cases. Toxicity was manageable after dose reduction, allowing patients
      to be re-treated for two to six courses without life-threatening toxicity or
      toxic deaths. Unfortunately, the duration of response was limited even among
      complete responders. Further trials of this combination in patients with MBC
      should explore improvements in this study regimen.

PMID- 9144688
TI  - Doxorubicin and paclitaxel (sequential combination) in the treatment of advanced
      breast cancer.
AB  - Based on preclinical data, we designed a phase I/II clinical trial to determine
      the efficacy and toxicity of doxorubicin followed by paclitaxel in the treatment
      of advanced breast cancer (either untreated or relapsed after adjuvant therapy).
      In the phase I dose-finding study, 19 enrolled patients received bolus
      doxorubicin (50 mg/m2) and, after a 16-hour interval, a three-hour infusion of
      paclitaxel in escalating doses from 130 to 250 mg/m2, increased by 30-mg/m2
      increments for each dose-level group. The first dose level group (paclitaxel 130
      mg/m2) included three patients. The other dose level groups included four
      patients. Treatment was repeated every three weeks for a maximum of eight cycles.
      The paclitaxel dose was escalated to 250 mg/m2 without reaching the maximum
      tolerated dose. In the 128 cycles assessable for toxicity, there were no relevant
      clinical signs or symptoms of cardiotoxicity. This absence of significant
      cardiotoxicity required confirmation in a phase II trial. Since a maximum
      tolerated dose of paclitaxel had not been reached during the first study and an
      increasing risk of neutropenia and peripheral neurotoxicity was feared if doses
      continued to escalate, a phase II confirmatory study was begun to evaluate
      treatment with fixed doses of doxorubicin (50 mg/m2) and paclitaxel (220 mg/m2),
      using the same schedule and interval as in phase I. The 13 patients enrolled in
      phase II received a total of 95 cycles of therapy; in 10 cycles (three patients)
      dose reductions were necessary because of toxicity. However, no significant
      clinical cardiotoxicity was observed in 12 of the 13 patients. One patient
      experienced an asymptomatic, transient decrease in left ventricular ejection
      fraction at a cumulative doxorubicin dose of 400 mg/m2. Overall clinical
      responses included 10 complete remissions (31.3%) and 15 partial remissions
      (46.9%) for an objective response rate of 78.1%. At 16 months' median follow-up,
      the median time to progression for all patients is nine months. The high response
      rate obtained in the phase I/II studies and, in particular, the absence of
      significant cardiotoxicity require confirmation in further clinical trials. To
      date, two confirmatory phase II trials are ongoing in our institutions.

PMID- 9144689
TI  - Paclitaxel and epirubicin as first-line therapy for patients with metastatic
      breast cancer.
AB  - Paclitaxel (Taxol), has aroused considerable interest for its high single-agent
      activity in breast cancer and novel mechanism of action. Epirubicin
      (Farmorubicin), the 4'epimer of doxorubicin (Adriamycin), also has high activity
      in breast cancer, with the advantage of a lower rate of toxic side effects
      especially cardiac effects-compared with its parent compound. The combination of
      paclitaxel and doxorubicin has yielded response rates between 63% and 94% in
      phase I/II studies, but authors reported severe cardiac toxic events. The goal
      for the current study was to evaluate the combination of paclitaxel and
      epirubicin, focusing mainly on cardiac toxicity. Of a total of 85 patients
      entered, 68 patients with metastatic breast cancer were evaluable. Nearly 20% had
      primary metastatic breast cancer with large tumors. Half had received adjuvant
      chemotherapy. Study medication in Group A consisted of 60 mg/m2 epirubicin given
      over 1 hour, followed by paclitaxel 175 mg/m2 as a 3-hour IV infusion. In Group
      B, 90 mg/m2 epirubicin was combined with 175 mg/m2 paclitaxel, delivered as for
      Group A. The main toxicity in both groups was neutropenia. In Group A, the
      paclitaxel dose could be escalated to 200 mg/m2 in 15 patients and to 225 mg/m2
      in 7 patients; dose reduction due to severe neutropenia was necessary in 11
      patients. No cardiac adverse events were reported in Group A. In Group B, only
      one patient could be escalated to 200 mg/m2 but three patients required a dose
      reduction. In this group, one patient had a decrease of left ventricular ejection
      fraction of more than 10% without any clinical signs. Of 43 patients in Group A
      and 25 in Group B, the response rate was 67% in Group A and 68% in Group B. The
      duration of response was 8.2 months in both groups. The combination of paclitaxel
      175 mg/m2 and epirubicin 60 mg/m2 or 90 mg/m2 can be safely administered. The
      response data were encouraging and further evaluation is warranted.

PMID- 9144690
TI  - Infusional 5-FU, folinic acid, paclitaxel, and cisplatin for metastatic breast
      cancer.
AB  - Our phase II study results demonstrating high efficacy and low toxicity for a
      weekly schedule of high-dose, 24-hour infusional 5-fluorouracil(5-FU)/folinic
      acid (HD5-FU/FA) in intensively pretreated patients with metastatic breast cancer
      prompted addition of paclitaxel (Taxol) to the regimen, for a phase I/II study of
      outpatient second-line treatment of metastatic breast cancer. That study further
      prompted the addition of cisplatin (Platinol) to the regimen for first-line
      treatment. So far, 28 patients with metastatic breast cancer have been evaluated.
      Pretreatment comprised adjuvant chemotherapy in 24 of 28 patients, but no prior
      chemotherapy for metastatic disease. Patients were treated with HD5-FU 2 g/m2 (24
      hour infusion) plus FA 500 mg/m2 (2-hour infusion prior to FU) weekly for 6 weeks
      (days 1, 8, 15, 22, 29, and 36); in addition, paclitaxel 175 mg/m2 (3-hour
      infusion) was administered on days 0 and 21 and cisplatin 50 mg/m2 (1-hour
      infusion) on days 1 and 22 prior to HD5-FU/FA, repeated every 50 days. Patients
      were treated as outpatients using Port-a-Cath systems and portable pumps.
      Neutropenia was common (67% World Health Organization grade 3) but mild to
      moderate in most patients and was of short duration. No hospitalizations were
      required because of febrile neutropenia, and no granulocyte colony-stimulating
      factor support was used. Aside from common total alopecia, nonhematologic
      toxicities consisted mainly of moderate myalgia, diarrhea, mucositis, and nausea
      and vomiting. Hand-foot syndrome and peripheral neuropathy were cumulative and
      occurred most commonly during the third treatment cycle, with mild-to-moderate
      expression. In 28 patients with bidimensionally measurable disease, 25% (7/28)
      attained a complete response, 57% (16/28) achieved partial response, 11% (3/28)
      had stable disease, and 7% (2/28) had disease progression. Overall response was
      82% (95% confidence interval, 66% to 100%). Eight of 28 patients are still
      receiving treatment. It is concluded that the combination of paclitaxel/cisplatin
      with weekly HD5-FU/FA appears to be effective in the first-line treatment of
      metastatic breast cancer. Preliminary results must be confirmed by the final
      analysis of response duration, time to progression, and survival.

PMID- 9144691
TI  - Melanoma in children and adolescents.
AB  - Melanoma is a life-threatening and rare malignancy in childhood and adolescence.
      Because it is so uncommon, melanoma may not be recognized readily or considered
      seriously in a differential diagnosis, resulting in delays in definitive
      treatment. We review melanoma occurring in 13 patients under 20 years of age who
      presented to a single tertiary care children's hospital. Five patients had
      nonmetastatic primary cutaneous melanoma, with Breslow thickness measurement
      ranging from 0.84 to 7.8 mm. Three patients had metastatic primary cutaneous
      melanoma, three had metastatic melanoma arising ina congenital giant nevus, and
      two had primary leptomeningeal melanoma. All of the patients were given
      definitive surgical treatment; some received adjunctive radiation therapy and
      chemotherapy. Overall 5-year survival rate was 40.0% for all cutaneous melanomas,
      which included 100% for clinical stage I disease, and 0% for clinical stage II
      and III disease. Both patients with primary leptomeningeal melanoma died an
      average of 6 months following diagnosis. Nonmetastatic primary cutaneous melanoma
      is a survivable disease if detected early and treated by surgical excision;
      metastatic and leptomeningeal disease were uniformly fatal. Types of melanoma,
      risk factors for melanoma, and the role of the dermatologist in primary
      prevention and detection are discussed.

PMID- 9144693
TI  - Nonlipidized juvenile xanthogranuloma: a histologic and immunohistochemical
      study.
AB  - Among all patients with a pathologic diagnosis of juvenile xanthogranuloma (JXG)
      seen at our institution from 1983 to 1994, we identified five patients with an
      unusual histologic pattern that differed from the classic juvenile
      xanthogranuloma (CJXG) with foamy cells and Touton giant cells. Four of these
      five cases, which we termed nonlipidized juvenile xanthogranuloma (NJXG), were
      seen in infants. The histologic features include a monomorphic infiltrate with
      absent or few foam cells and Touton giant cells. There is little inflammation,
      and mitotic figures are easily found. Four cases exhibit a diffuse sheetlike
      pattern while one is trabecular. Immunoperoxidase staining was done. All lesions
      are consistently positive for factor XIIIa as opposed to only focally positive or
      negative in CJXG and negative in Langerhans cell histiocytosis (LCH). The S-100
      was negative. NJXG represents an atypical histologic variant of JXG, which may
      suggest a malignant or aggressive tumor. The follow-up, however, indicates that
      these lesions behave in a fashion similar to those of CJXG. The differential
      diagnosis should be made with LCH, intradermal nevus, and reticulohistiocytosis.
      The immunoperoxidase findings help to differentiate NJXG from these entities.

PMID- 9144692
TI  - CTCL in patients under 20 years of age: a series of five cases.
AB  - The diagnosis of cutaneous T-cell lymphoma in patients under 20 years of age is
      extremely rare. We report five patients diagnosed before 20 years of age who
      illustrate the striking variations in clinical and histologic features as well as
      disease progression. We feel this information stresses the importance of multiple
      biopsies in young patients with chronic dermatoses.

PMID- 9144694
TI  - The efficacy of treatment with triamcinolone acetonide in calcinosis cutis
      following extravasation of calcium gluconate: a preliminary study.
AB  - Neonatal hypocalcemia is not an uncommon condition, especially in the premature
      neonate. It is effectively treated by intravenous administration of calcium
      gluconate. Complications of extravasation during intravenous infusion include
      localized calcification and occasionally necrosis. When this occurs, however,
      there is no specific mode of treatment except supportive management and skin
      graft. This experiment was designed to evaluate the efficacy and safety of
      treatment with triamcinolone acetonide in calcinosis cutis following
      extravasation of calcium gluconate. Initially, 2 cc of 10% calcium gluconate was
      injected subcutaneously into two rabbits at seven sites on the shaved skin of the
      back. Another two rabbits were injected at the same sites with 0.5 cc of
      triamcinolone acetonide (10 mg/dl) after injection of 2 cc of 10% calcium
      gluconate. As a control, 2 cc of normal saline was injected into another rabbit
      in the same manner. These five rabbits were observed over the next 7 weeks and
      underwent pathologic examination at various intervals (on days 1, 3, 8, 15, 30,
      37, 45). In the 10% calcium gluconate injected rabbits, nodules and large
      ulcerated lesions developed after 15 days. Multiple, linear, ulcerative and
      indurated masses were noted on day 37. The lesions healed progressively with a
      decrease in ulceration, and after 2 months, the masses disappeared gradually.
      Histologically, on day 15 calcium deposits were seen in the walls of the
      arteries, veins, dermis, and muscle fibers and epidermal necrosis was seen at the
      injection sites. From day 37 discharge of calcium deposits began to take place by
      means of transepidermal elimination. After 2 months, the calcium and mucin
      deposition was observed focally in the dermis. In the rabbits injected with 10%
      calcium gluconate and triamcinolone acetonide, mild erythema and induration were
      seen after day 15 at the injection sites; this gradually disappeared. After 30
      days the injection sites were normal in appearance. Histologically, at day 15
      calcium deposition was seen in the upper dermis, but after 1 month the injection
      sites were histologically normal. We suggest that intralesional injection of
      triamcinolone acetonide for the treatment of calcinosis cutis following
      extravasation of calcium gluconate is effective, probably due to its
      antiinflammatory effect and its role in facilitating the resorption of calcium in
      the tissue.

PMID- 9144695
TI  - Tyrosinemia type II: a challenge for ophthalmologists and dermatologists.
AB  - Tyrosinemia type II was suspected in a 13-month-old child with recurrent
      photophobia, tearing, and hyperkeratotic lesions on the palms and soles.
      Laboratory tests revealed high tyrosine levels in blood and urine. All the
      symptoms promptly improved after the institution of a low tyrosine diet. We
      emphasize the importance of an early diagnosis in order to avoid the risk of
      mental retardation in these patients.

PMID- 9144696
TI  - Neurologic abnormalities in two patients with facial hemiatrophy and sclerosis
      coexisting with morphea.
AB  - Progressive facial hemiatrophy or Parry-Romberg syndrome is a rare entity
      characterized by unilateral atrophy of the skin, subcutaneous tissue, and the
      underlying bony structures. This syndrome has many features of linear scleroderma
      en coup de sabre but is distinguished by more extensive involvement of the lower
      face and by only slight cutaneous sclerosis. We describe two unusual children
      with both atrophic and sclerotic changes of half of the face coexisting with
      multiple plaques of typical morphea. Both children developed neurologic
      disturbances with cranial magnetic resonance imaging (MRI) abnormalities 2 years
      and 15 years, respectively, after the onset of cutaneous lesions. Thus
      considering that it may not be possible to correlate impairment in neurologic
      function and cutaneous disease, as illustrated by our patients, we emphasize the
      importance of an accurate follow-up.

PMID- 9144698
TI  - A case of Bloom syndrome with conjunctival telangiectasia.
AB  - Bloom syndrome is a rare genodermatosis characterized by photosensitivity,
      telangiectasias, growth retardation and malignancies. Eye findings have rarely
      been mentioned in case reports of this syndrome. We report a child with Bloom
      syndrome who had pronounced bulbar conjunctival telangiectasia originally
      diagnosed as episcleritis. Bulbar telangiectasia are frequently described in
      other genodermatoses such as ataxia telangiectasia and hereditary hemorrhagic
      telangiectasia, but are infrequently noted in Bloom syndrome. Previously
      described eye findings in Bloom syndrome are reviewed and the differential
      diagnosis of bulbar telangiectasia is discussed.

PMID- 9144697
TI  - Bilateral abdominal aplasia cutis congenita associated with atrial septal defect:
      a case report.
AB  - A full-term infant girl who had bilateral, symmetrical, sharply defined,
      triangular-shaped ulcers on both sides of the umbilicus is described. A punch
      biopsy specimen showed histologic findings of aplasia cutis. Echocardiographic
      examination revealed primum-type atrial septal defect. To our knowledge, this
      association is the first of its kind to be reported in the literature.

PMID- 9144699
TI  - A new case of trichothiodystrophy associated with autism, seizures, and mental
      retardation.
AB  - We report a patient with trichothiodystrophy associated with autism, mental
      retardation, and seizures. The diagnosis was based on the presence of brittle
      hair, with a marked decrease in sulfur-rich amino acid content, and
      characteristic features such as "tiger tail" under polarizing microscopy and
      trichoschisis under scanning electron microscopy. Macroscopic alterations were
      mostly observed in the frontal and occipital hair, with only microscopic
      abnormalities in the occipital hair. We consider this an unusual expression of
      this disease.

PMID- 9144700
TI  - Lichen planus in a child requiring circumcision.
AB  - Lichen planus is a rare disorder in infants and children where it usually has the
      classical cutaneous pattern and only exceptionally involves the mucosa and skin
      appendages. A 9-year-old boy was referred to our department with a 4-month
      history of erythematous keratotic papules on the trunk and the upper and lower
      limbs. There were no signs of mucosal involvement. Subsequently white papules and
      striae, occasionally forming a lace like pattern, appeared on the penis and
      prepuce which quickly led to phimosis necessitating circumcision. Histologic
      examination of skin biopsy specimens and genital mucosa fragments confirmed the
      clinical diagnosis of lichen planus.

PMID- 9144701
TI  - Diagnosis and treatment of pustular disorders in the neonate.
AB  - The diagnosis of a pustular dermatosis occurring during the first months of life
      is usually based on clinical findings. However, some cases may require simple
      investigations including microscopic examination of pustular content, cultures,
      and skin biopsies. The main benign transient neonatal types of pustulosis include
      erythema toxicum neonatorum, infantile acropustulosis, transient neonatal
      pustular melanosis, and neonatal acne. The most common causes of infectious
      pustular skin lesions include bacterial infections, which may be initially
      localized (Staphylococcus aureus) or septicemic (with Listeria monocytogenes as
      the leading causitive agent); viral infections (herpes simplex, varicella-zoster,
      and cytomegalovirus infections); fungal infections (candidiasis); or parasitic
      disorders (scabies). The main objective of this article is to propose a
      systematic approach to pustular eruptions in the neonate. The need for
      investigating every neonate with pustules for an infectious disease is
      emphasized. The Tzanck smear, the Gram's stain, and a potassium hydroxide
      preparation are the most important quick diagnostic tests. The Tzanck smear is a
      very easy, rapid, and sensitive test for detection of a herpetic infection
      (multinucleated giant cells) as well as noninfectious pustular eruptions
      (eosinophils, neutrophils). Therefore the Tzanck smear should be the first test
      performed. Moreover, a Gram's stain and potassium hydroxide preparation should be
      performed in cases of neonatal pustular disorders to detect bacterial and fungal
      infections. The goal of this diagnostic approach is to spare a healthy neonate
      with a benign transient condition an invasive evaluation for sepsis, potentially
      harmful antibiotic therapy, and prolonged hospitalization, with its own inherent
      morbidity.

PMID- 9144702
TI  - Transverse leukonychia (Mees' lines) due to daunorubicin chemotherapy.
AB  - Transverse bands of leukonychia are reported in a 7-year-old boy following a 10
      day course of daunorubicin given for the treatment of lymphoblastic leukemia. A
      variety of other chemotherapies did not induce any nail changes in this patient.

PMID- 9144703
TI  - Itraconazole in the treatment of two young brothers with chronic mucocutaneous
      candidiasis.
AB  - We report on two children affected by chronic mucocutaneous candidiasis involving
      the mouth and all the nails who were successfully treated with itraconazole at
      200 mg/day for 2 months. This therapy produced a rapid cure of both candidal nail
      and mouth infections. The drug was very well tolerated, and routine laboratory
      monitoring during treatment did not reveal any abnormalities.

PMID- 9144704
TI  - What syndrome is this? Rapp-Hodgkin syndrome.

PMID- 9144705
TI  - Papular eruption on the elbows and trunk in an infant.

PMID- 9144706
TI  - Orf and erythema multiforme in a child.

PMID- 9144707
TI  - Management of nevus spilus with laser.

PMID- 9144708
TI  - Early outcomes after stereotactic radiosurgery for growing pilocytic astrocytomas
      in children.
AB  - To examine the role of stereotactic radiosurgery in the adjuvant management of
      children with growing and unresectable deep-seated pilocytic astrocytomas, we
      reviewed our experience in 9 patients. The tumors were located in the
      dorsolateral pons (n = 2), midbrain (n = 1, cerebellar peduncle (n = 2), thalamus
      (n = 1), temporal lobe (n = 1), hypothalamus (n = 1), and caudate nucleus (n =
      1). The mean tumor diameter was 16 mm (range, 11-25 mm). Seven patients had prior
      partial tumor resection, and 2 had a stereotactic biopsy. Two patients had failed
      fractionated radiotherapy and 7 were considered at risk for adverse radiation
      effects because of their age. The mean dose to the tumor margin at radiosurgery
      was 15 Gy (range, 12-18). During mean follow-up of 19 months (range 13-41
      months), there was a marked decrease in tumor size in 5 patients; 4 patients had
      no further growth. No early or delayed morbidity was associated with
      radiosurgery. Gamma knife radiosurgery proved a safe and effective therapeutic
      tool in the management of children with deep, small volume pilocytic
      astrocytomas. Because this tumor often appears well-delineated on contrast
      enhanced neuroimaging, we believe that conformal radiosurgical targeting
      accurately irradiates tumor cells. For small tumor volumes it can be used in
      place of fractionated larger-field radiotherapy. The ability to treat the tumor
      yet spare surrounding brain may reduce the surgical morbidity associated with
      attempted radical resection and the potential cognitive and endocrine
      disabilities associated with fractionated radiation therapy.

PMID- 9144709
TI  - Disappearing subdural hematomas in children.
AB  - Subdural hematomas in infants and young children are uncommon, usually occurring
      from nonaccidental trauma in infants or from trauma associated with motor
      vehicles. We report 4 children with apparent unilateral convexity subdural
      hematomas, 3 of which occurred from household falls and 1 occurring from a fall
      out of a window. These injuries were characterized by clinical symptoms
      consistent with the apparent forces involved, which were relatively minor in the
      first three instances. The clots resolved spontaneously within the first 1-2 days
      after injury. Such collections are likely located at least partly within the
      subarachnoid space, but may mimic more clinically significant subdural hematomas.
      Their recognition may influence decisions regarding both surgical evacuation and
      the likelihood of nonaccidental injury. Clinical and radiographic features
      distinguishing these 'disappearing subdurals' from more typical subdural
      hematomas are discussed.

PMID- 9144710
TI  - Experimental acute subdural hematoma in infant piglets.
AB  - Traumatic acute subdural hematoma is associated with high mortality in the
      pediatric population, yet the pathophysiology remains poorly understood. The
      objective of this study was to develop a pediatric model of acute subdural
      hematoma, and to evaluate the resultant histopathological changes in the brain.
      Ten 3-week-old piglets were studied. A 5-mm craniotomy was made in the right
      frontal skull. A small silastic tube was inserted through the underlying intact
      dura into the subdural space. A craniotomy was made posterior to the right
      coronal suture with underlying dura left intact (closed cranial window model).
      Injection of 5 ml autologous, nonheparinized blood was accomplished through the
      silastic tube. Animals were sacrificed after 72 h or 1 week. During the subdural
      injection, intracranial pressure rose to 62 +/- 8 mm Hg, and returned to baseline
      within 1 h of surgery. Mean arterial blood pressure increased transiently. Cresyl
      violet and hematoxylin and eosin staining demonstrated extensive areas of white
      matter necrosis under the hematoma after 72 h survival (n = 7). Zones of necrosis
      were also noted in cortex, but were less extensive than those seen in white
      matter. These results differ from adult rodent models in which cortex is
      primarily affected. This is the first reported pediatric model of traumatic acute
      subdural hematoma. This model can be used in future studies to investigate
      pharmacological or other therapies which may improve outcome after this type of
      injury.

PMID- 9144711
TI  - Postneurulation rapid brain growth represents a critical time for encephalocele
      formation: a chick model.
AB  - Current theory regarding the pathogenesis of encephaloceles suggests that the
      defect occurs after neurulation is completed in which brain tissue herniates
      through defective mesodermal elements necessary for skull modeling. To better
      delineate the mechanisms of encephalocele development, we performed a variety of
      microsurgical manipulations in the developing cranium of the chick embryo during
      the postneurulation period of early rapid brain growth. The results of the study
      revealed that encephaloceles could be induced in 78% of chick embryos manipulated
      at stage 26 that had evidence of marked decompression of the primitive ventricle.
      On the other hand, control embryos or embryos manipulated without ventricular
      decompression at stage 26 did not develop encephaloceles (0 of 32). Embryos with
      decompression of the primitive ventricle treated at earlier stages (20-24) showed
      only a 5% incidence of encephaloceles. These findings suggest that there is both
      a critical time point during postneurulation rapid brain growth when
      encephaloceles are prone to occur and a mesenchymal defect associated with
      decompression of the primitive ventricle that must be present to induce
      encephaloceles.

PMID- 9144712
TI  - Immunohistochemically identifiable tissue plasminogen activator in cavernous
      angioma: mechanism for re-hemorrhage and lesion growth.
AB  - The mechanisms governing growth of cavernous angiomas of the brain and their
      propensity to hemorrhage remain unknown. Repetitive hemorrhage with
      neovascularization during clot organization and maturation of new vessels into a
      larger cavernous angioma has been hypothesized as one mechanism. This hypothesis
      is largely based on the histopathological similarity between the organizing clot
      surrounding cavernous malformations and the organizing phase of the membranes
      surrounding chronic subdural hematoma. The presence of tissue plasminogen
      activator (TPA) in the vascular endothelium of vessels contained within chronic
      subdural membranes has been used to argue that an intrinsic thrombolytic process
      is responsible, in part, for rebleeding within chronic subdural cavities. By
      analogy, we sought to identify whether TPA is located in tissues in and around
      cavernous angiomas. Cavernous malformations, surgically removed and
      pathologically confirmed by standard staining techniques, were
      immunohistochemically stained for TPA. Eleven of thirteen lesions (85%) studied
      contained vascular endothelial cells which stained for TPA. Of the 2 lesions
      which did not contain TPA, 1 was non-hemorrhagic and calcified; 7 of 11 (64%)
      lesions which contained TPA presented clinically with hemorrhage. These data
      support the hypothesis that a local thrombolytic process may be responsible for
      the frequent hemorrhagic nature of cavernous angiomas. Alternatively, since local
      elaboration of TPA is common to both chronic subdural membranes and cavernous
      angiomas, this finding may represent a more global characteristic of fibrinolytic
      homeostasis in cerebral tissues.

PMID- 9144713
TI  - The Currarino triad: its importance in pediatric neurosurgery.
AB  - Currarino's triad is a hereditary condition diagnosed when three abnormalities
      are noted: (1) an anorectal malformation; (2) an anterior sacral defect, and (3)
      a presacral mass. This condition often presents with symptoms related to the
      presacral mass or with an incidental finding of a sacral anomaly on plain
      radiographs. Presented here are 2 cases of Currarino's triad noted in siblings,
      both of whom underwent surgery for anorectal malformations in infancy. The
      importance of early diagnosis and treatment of this condition and the need for
      genetic counseling are emphasized.

PMID- 9144714
TI  - Bilateral congenital anomalies of the extracranial vertebral artery: management
      with balloon therapy.
AB  - Congenital anomalies of the vertebral artery, including aneurysms and
      fenestrations, or partial duplication of the extracranial vertebral artery are
      rarely seen. Presented here is an unusual case of bilateral congenital anomalies
      of the extracranial vertebral arteries. The right vertebral artery demonstrated
      an aneurysm and the left a partial duplication. The aneurysm was felt to be the
      source of the embolic phenomenon to the posterior circulation. This was treated
      with detachable balloon catheter placement.

PMID- 9144715
TI  - De novo familial cavernous malformation presenting with hemorrhage 12.5 years
      after the initial hemorrhagic Ictus: natural history of an infantile form.
AB  - Cerebral cavernous malformations are congenital, non-neoplastic lesions, but they
      are known for their potential for growth. De novo lesion genesis is exceptional
      and occurs more commonly with the familial form of the disease. We report the
      case of a 13-year-old Caucasian boy with a positive family history, who underwent
      surgery for a left parietal hemorrhage during the 1st year of life and who
      recently presented with a new hemorrhage in the left temporal lobe quite distant
      from the previous hematoma bed. Both hemorrhages were caused by cavernous
      malformations. Sequential magnetic resonance scans prior to the recent
      presentation failed to disclose the growth of the new lesion. We reviewed the
      literature for mechanisms of new lesion formation.

PMID- 9144716
TI  - Osteolysis circumscripta evanescans.
AB  - A circumscribed radiolucent skull abnormality was detected on plain radiographs
      obtained to evaluate minor cranial trauma in a young boy. The lesion disappeared
      on follow-up X-rays performed later in the day. Analysis of the case revealed
      that the lesion was an artifact resulting from a superimposed hole in a wooden
      backboard on which the patient was X-rayed initially. Radiographs shot through a
      protective backboard may be misleading, and not all abnormalities identified
      belong to the patient.

PMID- 9144717
TI  - Intestinal obstruction caused by extraperitoneal cerebrospinal fluid collection.
AB  - External compression caused by a massive extraperitoneal cerebrospinal fluid
      collection lead to intestinal obstruction in a 3-year-old child who had
      previously had a ventriculoperitoneal shunt for treatment of hydrocephalus.
      Radiological findings and ways of preventing this situation are discussed. A
      useful diagnostic radiological sign, the "coiling sign', indicating shunt
      misplacement at the peritoneal level, is also described.

PMID- 9144718
TI  - Concerning the articles by Dias MS et al. Pediatr Neurosurg 1996;24:61-68 and
      1996;24:69-73. Ethical considerations regarding scientific publications.

PMID- 9144719
TI  - Capillary electrophoresis in pharmaceutical analysis.
AB  - Capillary electrophoresis (CE) is a separation technique particularly suited to
      the analysis of pharmaceutical compounds. This review offers a detailed
      discussion of the four common modes of detection coupled to CE-UV absorption,
      fluorescence, electrochemical, and mass spectrometry-and gives examples of the
      use of these methods in pharmaceutical analyses. Sample preparation and
      pretreatment techniques used for CE separations are described, as well as methods
      of preconcentration including hydrophobic retention, affinity concentration,
      sample stacking, and isotachophoresis. The use of affinity CE, chiral CE, and
      capillary gel electrophoresis for analysis of pharmaceuticals is covered in
      detail, and recent advances in capillary electrochromatography and CE on a chip
      are also discussed.

PMID- 9144720
TI  - Sequence alignments of the H(+)-dependent oligopeptide transporter family PTR:
      inferences on structure and function of the intestinal PET1 transporter.
AB  - PURPOSE: To study the structure and function of the intestinal H+/ peptide
      transporter PET1, we compared its amino acid sequence with those of related
      transporters belonging to the oligopeptide transporter family PTR, and with more
      distant transporter families. METHODS: We have developed a new approach to the
      sequence analysis of proteins with multiple transmembrane domains (TMDs) which
      takes into account the repeated TMD-loop topology. In addition to conventional
      analyses of the entire sequence, each TMD and its adjacent loop residues (= TMD
      segments) were analyzed separately as independent structural units. In
      combination with hydropathy analysis, this approach reveals any changes in the
      order of the TMD segments in the primary structure and permits TMD alignments
      among divergent structures even if rearrangements of the order of TMD segments
      have occurred in the course of evolution. RESULTS: Alignments of TMD segments
      indicate that the TMD order in PTR transporters may have changed in the process
      of evolution. Consideration of such changes permits the alignment of homologous
      TMD segments from PTR transporters belonging to distant akaryotic and eukaryotic
      phyla. Multiple alignments of TMDs reveal several highly conserved regions that
      may play a role in transporter function. In comparing the PTR transporters with
      other transporter gene families, alignment scores using the entire primary
      structure are too low to support a finding of probable homology. However,
      statistically significant alignments were observed among individual TMD segments
      if one disregards the order in which they occur in the primary structure.
      CONCLUSIONS: Our results support the hypothesis that the PTR transporters may
      have evolved by rearrangement, duplication, or insertions and deletions of TMD
      segments as independent modules. This modular structure suggests new alignment
      strategies for determining functional domains and testing relationship among
      distant transporter families.

PMID- 9144721
TI  - Guanidine transport in a human choriocarcinoma cell line (JAR).
AB  - PURPOSE: Many endogenous substances and xenobiotics are organic cations.
      Transplacental transport of organic cations is an important determinant of the
      delivery of these compounds to the fetus. The aim of this study was to determine
      the mechanisms of organic cation transport using the human choriocarcinoma cell
      line (JAR) as a model system with [14C]guanidine as a ligand. METHODS: Uptake
      studies of [14C]guanidine were carried out in JAR cell monolayers on day 2 after
      plating. RESULTS: [14C]guanidine uptake was temperature dependent, saturable (Km
      = 167 microM) and inhibited by many organic cations including amiloride,
      cimetidine, quinine, quinidine and nicotine. [14C]guanidine uptake exhibited a
      counterflux phenomenon indicative of a carrier-mediated process. The uptake of
      [14C]guanidine was sodium and pH-independent and could be driven by an inside
      negative membrane potential difference. CONCLUSIONS: This is the first
      demonstration of an electrogenic guanidine transporter in a human cell culture
      model. This transporter may play a role in the transplacental transport of many
      clinically used drugs and xenobiotics.

PMID- 9144722
TI  - Taurine transport in cultured choroid plexus.
AB  - PURPOSE: Taurine, a beta-amino acid, is a neuromodulator which interacts
      functionally with the glycinergic, GABAergic, cholinergic and adrenergic systems.
      Although a continuous cell culture model is not available for the choroid plexus
      epithelia, we recently described a primary cell culture of rabbit choroid plexus
      epithelia. The goal of the current study was to determine the suitability of this
      primary cell culture for the study of the Na(+)-taurine transporter in the rabbit
      choroid plexus. METHODS: A primary cell culture of rabbit choroid plexus
      epithelial cells was grown on semi-permeable filters and kinetics of 3H-taurine
      uptake were ascertained. RESULTS: Taurine transport in the cultured choroid
      plexus cell was Na(+)-dependent and saturable (Km = 156 microM). The beta-amino
      acids, beta-alanine and taurine, significantly inhibited Na(+)-driven taurine
      transport whereas L-alanine partially inhibited taurine transport in the cultured
      cells. In addition, we observed that the activity of the Na(+)-taurine
      transporter is affected by exposure to taurine in the media. CONCLUSIONS: These
      results-demonstrate that a Na(+)-taurine transporter with characteristics similar
      to those in the intact tissue is expressed in cultured choroid plexus epithelial
      cells. The transporter may undergo adaptive regulation and play a role in taurine
      homeostasis in the central nervous system.

PMID- 9144723
TI  - Molecular mobility of supercooled amorphous indomethacin, determined by dynamic
      mechanical analysis.
AB  - PURPOSE: To determine the viscosity and the frequency-dependent shear modulus of
      supercooled indomethacin as a function of temperature near and above its glass
      transition temperature and from these data to obtain a quantitative measure of
      its molecular mobility in the amorphous state. METHODS: Viscoelastic measurements
      were carried with a controlled strain rheometer in the frequency domain, at 9
      temperatures from 44 degrees to 90 degrees C. RESULTS: The viscosity of
      supercooled indomethacin shows a strong non-Arrhenius temperature dependence over
      the temperature range studied, indicative of a fragile amorphous material.
      Application of the viscosity data to the VTF equation indicates a viscosity of
      4.5 x 10(10) Pa.s at the calorimetric Tg of 41 degrees C. and a T0 of -17 degrees
      C. From the complex shear modulus and the Cole-Davidson equation the shear
      relaxation behaviour is found to be non-exponential, and the shear relaxation
      time at Tg is found to be approximately 100 sec. CONCLUSIONS: Supercooled
      indomethacin near and above its Tg exhibits significant molecular mobility, with
      relaxation times similar to the timescales covered in the handling and storage of
      pharmaceutical products.

PMID- 9144724
TI  - Effect of compaction temperature on consolidation of amorphous copolymers with
      different glass transition temperatures.
AB  - PURPOSE: The purpose of this study was to relate the combination of glass
      transition temperature (Tg) and temperature of measurement with the mechanical
      and compaction properties of some test materials. METHODS: Copolymers with
      different Tg'S were synthesised by free radical copolymerisation of methyl
      methacrylate with lauryl methacrylate. Elastic moduli were measured by dynamic
      mechanical analysis at different strain rates and temperatures. Compaction
      experiments were performed at different compaction speeds and temperatures.
      RESULTS: The difference between temperature of measurement and Tg appears to
      determine both elastic modulus and yield strength completely. They both decrease
      with decreasing difference between temperature of measurement and Tg and increase
      with strain rate. At temperatures of measurement higher than the Tg the elastic
      modulus is extremely low because the materials behave as rubbers. Consequently,
      the amount of energy stored during compaction decreases when the compaction
      temperature approaches the Tg and increases with strain rate. When the compaction
      temperature is higher than the Tg, the amount of stored energy is extremely
      large. The compaction experiments show that the final tablet porosity is
      completely determined by stress relaxation phenomena. Consequently, the final
      tablet porosity follows exactly the same relation as that of stored energy.
      CONCLUSIONS: The final tablet porosity is unequivocally determined by the amount
      of stored energy. This implies that tablet production at a temperature of about
      20 K under the glass transition temperature of the material yields tablets with
      minimum porosity.

PMID- 9144725
TI  - The stability of recombinant human growth hormone in poly(lactic-co-glycolic
      acid) (PLGA) microspheres.
AB  - PURPOSE: The development of a sustained release formulation for recombinant human
      growth hormone (rhGH) as well as other proteins requires that the protein be
      stable at physiological conditions during its in vivo lifetime. Poly(lactic-co
      glycolic acid) (PLGA) microspheres may provide an excellent sustained release
      formulation for proteins, if protein stability can be maintained. METHODS: rhGH
      was encapsulated in PLGA microspheres using a double emulsion process. Protein
      released from the microspheres was assessed by several chromatrographic assays,
      circular dichroism, and a cell-based bioassay. The rates of aggregation,
      oxidation, diketopiperazine formation, and deamidation were then determined for
      rhGH released from PLGA microspheres and rhGH in solution (control) during
      incubation in isotonic buffer, pH 7.4 and 37 degrees C. RESULTS: rhGH PLGA
      formulations were produced with a low initial burst (< 20%) and a continuous
      release of rhGH for 30 days. rhGH was released initially from PLGA microspheres
      in its native form as measured by several assays. In isotonic buffer, pH 7.4 and
      37 degrees C, the rates of rhGH oxidation, diketopiperazine formation, and
      deamidation in the PLGA microspheres were equivalent to the rhGH in solution, but
      aggregation (dimer formation) occurred at a slightly faster rate for protein
      released from the PLGA microspheres. This difference in aggregation rate was
      likely due to the high protein concentration used in the encapsulation process.
      The rhGH released was biologically active throughout the incubation at these
      conditions which are equivalent to physiological ionic strength and pH.
      CONCLUSIONS: rhGH was successfully encapsulated and released in its fully
      bioactive form from PLGA microspheres over 30 days. The chemical degradation
      rates of rhGH were not affected by the PLGA microspheres, indicating that the
      internal environment of the microspheres was similar to the bulk solution. After
      administration, the microspheres should become fully hydrated in the subcutaneous
      space and should experience similar isotonic conditions and pH. Therefore, if a
      protein formulation provides stability in isotonic buffer, pH 7.4 and 37 degrees
      C, it should allow for a safe and efficacious sustained release dosage form in
      PLGA microspheres.

PMID- 9144726
TI  - Effect of temperature history on the freeze-thawing process and activity of LDH
      formulations.
AB  - PURPOSE: The purpose of the study was to investigate the effect of freeze-thawing
      processes with different temperature histories on thermal transformations and on
      protein activity of lactate dehydrogenase (LDH) formulations. Polyethylene glycol
      (PEG 6000) and maltodextrin were used as cryoprotectants. METHODS: The thermal
      characterization was made by oscillating DSC (ODSC). LDH activity assays were
      performed spectrophotometrically. RESULTS: The crystallization of the solutions
      and the melting of the frozen samples occurred at fairly constant heat of
      crystallisation and heat of fusion values and temperatures. The main difference
      between the two investigated temperature cycles was an exothermic peak at -45
      degrees C, which might reflect the transition between the cubic and hexagonal ice
      structures. When PEG was added to the system an additional endothermic peak
      appeared at -15 degrees C in the heating program. It was transformed into the
      shape of a glass transition at the same temperature when the heating rate was
      increased. The degree of crystallinity of the samples was evaluated as the quota
      between the Cp component of heat of transformation and the total heat of
      transformation values. Only minor differences between the two temperature
      histories and between the samples were observed. The cp component of the melting
      endotherm revealed a complex melting process with two overlapping endothermic
      transformations. The good protein protecting ability of PEG obtained when cooling
      and heating rate was low, was greatly reduced with increasing rate. The addition
      of maltodextrin to PEG-containing solutions lowered the activity recovery.
      CONCLUSIONS: The endothermic transformation of a PEG-ice structure at -15 degrees
      C in the heating process is strongly correlated to the protective ability of PEG
      6000 in the freeze-thawing process of LDH. To obtain the highest protein activity
      after the freeze-thawing process, the formulation shall be transformed by a low
      cooling and heating rate. The crystallinity of the system melting at about 2
      degrees C is independent of temperature history. The cp component of the melting
      endotherm, however, shows a complex transformation, where two phases of different
      crystallinity and stability might be involved.

PMID- 9144727
TI  - Spray dried powders and powder blends of recombinant human deoxyribonuclease
      (rhDNase) for aerosol delivery.
AB  - PURPOSE: We have used rhDNase to investigate the feasibility of developing a dry
      protein powder aerosol for inhalation delivery. METHODS: Powders of rhDNase alone
      and with sodium chloride were prepared by spray drying. Powder blends were
      obtained by mixing (tumbling and sieving) pure rhDNase powder with 'carrier'
      materials (lactose, mannitol or sodium chloride). The weight percent of drug in
      the blends was between 5 and 70%. The particle size distributions and
      crystallinity of the spray dried powders were obtained by laser diffraction and X
      ray powder diffraction, respectively. Particle morphology was examined by
      scanning electron microscopy. The ability of the powders and powder blends to be
      dispersed into respirable aerosols was measured using a Rotahaler connected to a
      multistage liquid impinger operating at 60 L/min. RESULTS: Pure rhDNase powder
      was quite cohesive with a fine particle fraction (FPF or "respirable fraction': %
      wt. of particles < 7 microns in the aerosol cloud) of about 20%. When particles
      also contained NaCl, the powders were dispersed better to form aerosols. A linear
      relationship was observed between the NaCl content and FPF for a similar primary
      size (approximately 3 microns volume median diameter) of particles. The particle
      morphology of these powders varied systematically with the salt content. For the
      blends, SEM revealed a monolayer-like adhesion of the fine drug particles to the
      carriers at drug contents > or = 50% wt. An overall 2-fold increase in FPF of
      rhDNase in the aerosol cloud was obtained for all the blends compared to the pure
      drug aerosols. CONCLUSIONS: The aerosol properties of spray dried rhDNase powders
      can be controlled by incorporation of a suitable excipient, such as NaCl, and its
      relative proportion. Coarse carriers can also enhance the performance of rhDNase
      dry powder aerosols.

PMID- 9144728
TI  - Influence of metering chamber volume and water level on the emitted dose of a
      suspension-based pMDI containing propellant 134a.
AB  - PURPOSE: To determine the influence of metering chamber volume of a valve and
      water content of an aerosol formulation containing propellant 134a on dose
      delivery through the valve (DDV) and aerodynamic particle size distribution of
      the emitted dose. METHODS: The drug was admixed with ethanol, sonicated, and
      metered into cans. Valois DF10 RC valves were crimped onto the cans and
      propellant 134a was gassed through the valve. The DDV was determined using a
      dosage sampling tube. Aerodynamic particle size distributions were determined by
      cascade impaction. The water content was determined by Karl Fisher titration.
      RESULTS: The DDV increased linearly and the aerodynamic particle size
      distribution was not influenced as the metering chamber volume of the valve was
      increased. More drug was emitted from the valve from the initial actuations of
      the can than from the end. Valves with larger metering chamber volumes
      demonstrated less variability in DDV than those with smaller metering chamber
      volumes for the initial actuations. The DDV determined for actuations at the end
      of the can decreased as water was added extemporaneously. The mass median
      aerodynamic diameter (MMAD) increased as the water level was increased in the
      formulation. The geometric standard deviation (GSD) and percent respirable
      fraction (RF) were not influenced by metering chamber volume or water content.
      CONCLUSIONS: The valve chosen for the development of pressurized metered dose
      inhaler (pMDI) formulations with propellant HFA 134a must be investigated to
      determine the uniformity of drug delivery. The presence of water influences the
      characteristics of the emitted dose.

PMID- 9144729
TI  - Effect of sodium bicarbonate amount on in vitro indomethacin release from self
      setting carbonated-apatite cement.
AB  - PURPOSE: In the present study, to develop a drug delivery system with higher
      bioactivity in hard tissues by using the self-setting bioactive carbonate apatite
      cement, we have investigated the effects of sodium bicarbonate content on the in
      vitro drug release from a self-setting bioactive carbonate apatite cement
      containing indomethacin (IMC). METHODS: The cement powder systems constituted an
      equimolar mixture of tetracalcium phosphate (Ca4(PO4)2O) and dicalcium phosphate
      dihydrate (CaHPO4.2H2O), hydroxyapatite (HAP, Ca10(PO4)6(OH)2) seed crystals and
      sodium bicarbonate. Two types of 2% IMC loaded-cements were prepared as follows,
      one containing 0% HAP seed crystal and 0-10% sodium bicarbonate, and the other
      containing 40% HAP seed crystal and 0-10% sodium bicarbonate. The drug release
      profiles from 2% IMC loaded-cements were measured in simulated body fluid at pH
      7.25 and 37.0 degrees C. RESULTS: The drug release profiles from the cement
      matrix systems with or without seed crystals were estimated using a moment
      analysis computer program. The mean drug release time (MDT) and the time required
      for 50% drug release of the cement containing 0 and 40% seed crystal decreased
      with an increase of sodium bicarbonate. Furthermore, after the drug release the
      total pore volume of the cement matrix, as measured by mercury porosimetry,
      increased with an increase of sodium bicarbonate. CONCLUSIONS: MDT and T50's were
      a function of adding the amount of sodium bicarbonate. The results of the
      relationship between the micropore distribution, total volume of pores after drug
      release and drug release supported the hypothesis that the variation in drug
      release from the cements resulting from the addition of sodium bicarbonate was
      mainly due to an increase in the diffusion of the drug in the micropores of the
      cement by dissolution or erosion of the cement matrix.

PMID- 9144730
TI  - Textural analysis and flow rheometry of novel, bioadhesive antimicrobial oral
      gels.
AB  - PURPOSE: This study examined the rheological and textural characteristics
      (hardness, compressibilty, adhesiveness and cohesiveness) of bioadhesive oral
      gels containing the antimicrobial agent chlorhexidine. METHODS: Textural analysis
      was performed using a Stable Micro Systems texture analyser (model TA-XT 2) in
      texture profile analysis (TPA) mode. In this, an analytical probe was twice
      compressed into each formulation to a defined depth (15 mm) and at defined rates
      (2, 4, 6, 8, 10 mm s-1), allowing a delay period (15 s) between the end of the
      first and beginning of the second compressions. Flow rheograms were performed
      using a Carri-Med CSL2-100 rheometer with parallel plate geometry under
      controlled shearing stresses at 20.0 +/- 0.1 degrees C. RESULTS: All formulations
      exhibited pseudoplastic flow with thixotropy. Increasing concentrations of each
      polymer significantly increased formulation hardness, compressibility,
      adhesiveness and zero-rate viscosity. Increased hardness and compressibility were
      due to the attendent increased viscosities of these formulations. Increased
      adhesiveness was related to the concentrations of the (bioadhesive) polymers
      employed in these formulations and, in addition, was dependent on the physical
      state of polycarbophil. Formulation viscosity contributed to product
      adhesiveness, reflecting the importance of product rheology on this parameter.
      Decreased formulation cohesiveness, observed as the concentrations of the PVP, PC
      and HEC (3-5% w/w) were increased, was due an increase in semi-solid character.
      Numerical values of hardness, compressibility and adhesiveness were affected by
      the choice of probe speed, a parameter related to rate of shear in flow
      rheometry. Statistical interactions were observed and were assigned to the
      effects of HEC on the physical state of PVP (dissolved or dispersed) and PC
      (swollen or unswollen). CONCLUSIONS: This study has demonstrated both the
      applicability of textural analysis for the mechanical characterisation of
      bioadhesive semi-solid gel systems and, additionally, the direct influence of
      viscosity on the parameters defined by textural analysis, namely, hardness,
      compressibility and adhesiveness.

PMID- 9144731
TI  - Cytotoxicity of solid lipid nanoparticles as a function of the lipid matrix and
      the surfactant.
AB  - PURPOSE: Assessment of the in vitro cytotoxicity of solid lipid nanoparticles
      (SLNs) as a function of lipid matrix (Dynasan 114, Compritol ATO 888), and
      stabilizing surfactant (poloxamers, Tween 80, soya lecithin, and sodium dodecyl
      sulphate). Comparison with other colloidal carriers should determine their
      potential use in the clinic. METHODS: SLNs were produced by high pressure
      homogenisation. Cytotoxicity was assessed by measuring the viability of HL60
      cells and human granulocytes after incubation with SLNs. Particle internalisation
      was quantified by chemiluminescence measurements. RESULTS: The nature of the
      lipid had no effect on viability; distinct differences were found for the
      surfactants. Binding to the SLN surface reduced markedly the cytotoxic effect of
      the surfactants, e.g., up to a factor of 65 for poloxamer 184. The permanent HL60
      cell line-differentiated from cells with granulocyte characteristics by retinoic
      acid treatment-yielded results identical to freshly isolated human granulocytes.
      In general, the SLNs showed a lower cytotoxicity compared to
      polyalkylcyanoacrylate and polylactic/glycolic acid (PLA/ GA) nanoparticles.
      CONCLUSIONS: Because the results are identical when using human granulocytes,
      differentiated HL60 cells can be used as an easily accessible in vitro test
      system for i.v. injectable SLN formulations. The SLNs appear suitable as a drug
      carrier system for potential intravenous use due to their very low cytotoxicity
      in vitro.

PMID- 9144732
TI  - Splenic trapping of nanoparticles: complementary approaches for in situ studies.
AB  - PURPOSE: To identify more accurately in the spleen, the areas and the cells where
      nanoparticulate carriers were taken up from the blood flow, a series of
      complementary approaches were used. METHODS: First, in and ex vivo examination of
      the whole spleen led to a global view of all the trapping areas. Then,
      histological studies on frozen sections of the same organ allowed for a more
      precise localization of these areas and image analysis gave an evaluation of
      tissue distribution of the nanoparticles. Finally, immunological and
      enzymological characteristics of the capturing cells were determined in situ,
      using monoclonal antibodies (F4/80 and anti-sialoadhesin) and cytochemical
      reactions (esterases and acid phosphatase). Furthermore incubation of spleen
      slices with different nanoparticles was used so as to know if the capture was due
      to a high capturing capacity of these cells or to a high blood flow in their
      vicinity. RESULTS: It was shown that more than 90% of the splenic capture was
      localized in the marginal zone of the follicles. The capturing cells form a
      special population of macrophages inserted in a reticular meshwork, showing low
      esterase and acid phosphatase activities, giving faint or no reaction with F4/80
      or anti-sialoadhesin antibodies. The circulating nanoparticles were quickly
      trapped with rather low specificity by these cells. CONCLUSIONS: Combination of
      coherent approaches allowed for the tracking of capturing cells from in vivo
      observations to their in situ identification on immunological and enzymological
      criteria.

PMID- 9144733
TI  - Development of a statistical model for the formation of poly [acryloyl
      hydroxyethyl starch] microspheres.
AB  - PURPOSE: To develop a mathematical model for predicting the molecular weight
      between crosslinks, Mc, of poly[Acryloyl Hydroxyethyl Starch] (Ac-HES)
      microspheres system and to identify and evaluate the key microsphere preparation
      parameters which affect the Mc of the formed microsphere structure based on the
      developed model. METHODS: Link probability generating functions (LPGFs) based on
      the classical branching theory were used to derive a model for the calculation of
      Mc for the Ac-HES system. Based on the developed model, simulation was made to
      study the effects of the microsphere preparation variables on Mc of the formed
      microspheres. The process variables were the degree of derivatization (DD) of the
      Ac-HES, the molar ratio (MR) of the Ac-HES to acrylamide monomer, the fractional
      conversion of the unsaturation (alpha), the initiator efficiency (f), the molar
      concentration of initiator (I), the fraction of intramolecular cyclization (c),
      and the total weight of the reactable monomer and polymer (s). RESULTS: A model
      to describe the crosslinking reaction of Ac-HES system and predict Mc was
      developed. Simulation based on the model showed that Mc decreased as alpha
      increased and reached a limiting value before total conversion. At constant
      alpha, Mc initially decreased with MR to a minimum and then increased with MR;
      while Mc decreased monotonically with DD. I and c affected Mc only at very low
      alpha and changes in s and f had no effect on Mc. CONCLUSIONS: Simulation based
      on the model suggested that the most important microsphere preparation parameters
      influencing Mc of the Ac-HES system are the number of functional groups on the Ac
      HES (DD) and the stoichiometry (MR) of the crosslinking reaction.

PMID- 9144734
TI  - Evaluation of a statistical model for the formation of poly [acryloyl
      hydroxyethyl starch] microspheres.
AB  - PURPOSE: To characterize the network structure of Poly(Acryloyl Hydroxyethyl
      Starch) (Ac-HES) microspheres and test the theoretical model and the hypothesis
      that the rate of swelling of microspheres is inversely related to the extent of
      crosslinking. METHODS: Microspheres were prepared with varying degrees of
      derivatization (DD) and molar ratios (MR) and subjected to the characterization
      of matrix structure by dynamic and equilibrium swelling studies utilizing direct
      microscopic observation and the Flory-Rehner equation. The dependence of average
      molecular weight between crosslinking Mc, on DD and MR were compared to test the
      validity of the model. RESULTS: Study of the dependence of Mc on the microspheres
      preparation parameters, DD and MR, showed that at constant MR, the Mc decreased
      with DD, while at constant DD, the Mc initially decreased with MR to a minimum,
      and then increased with MR, complying with the model prediction. Dynamic swelling
      of microspheres showed a monotonical increase to equilibrium size featured by two
      time variables, Tp and Teq, that were dependent on Mc; this permitted a
      conceptual view of the general structure of the Ac-HES microspheres. The Mc,
      which was more accurately determined by the weight method (as opposed to volume
      method), was independent of the size of microspheres although there was evidence
      of variation among particles within a batch. CONCLUSIONS: The results validated
      the model in describing the polymerization/crosslinking reaction of the Ac-HES
      microsphere system and suggested that Mc is the principal factor in controlling
      release.

PMID- 9144735
TI  - Non-polarized secretion of mouse interferon-beta from gene-transferred human
      intestinal Caco-2 cells.
AB  - PURPOSE: The intestinal epithelium is considered to be a feasible target for
      somatic gene therapy. To this end, Caco-2 cells derived from human colon
      carcinoma were transfected with a mouse interferon-beta (IFN-beta) expression
      vector and several stable sublines were established; this hetero-specific
      cytokine allows unexpected cellular effects to be avoided. Using the highest
      mouse IFN-beta-producing sublines, the mode of IFN secretion was examined.
      METHODS: The secretion polarity of mouse IFN-beta in its gene-transduced Caco-2
      sublines was studied in a bicameral culture system in which the chambers were
      separated by microporous filters. RESULTS: Mouse IFN-beta was secreted to the
      same extent from both apical and basolateral surfaces of the transduced cells
      regardless of cell aging. CONCLUSIONS: These results suggest that in the
      intestinal epithelium exogenous gene products such as IFNs can be delivered to
      both the luminal and blood sides in vivo. Thus, the intestinal epithelium may be
      suitable for systemic and local delivery of therapeutic proteins by gene
      transfer.

PMID- 9144736
TI  - Analysis of drug permeation across Caco-2 monolayer: implication for predicting
      in vivo drug absorption.
AB  - PURPOSE: The aim of the present work is to characterize in vitro drug permeation
      processes across Caco-2 monolayer and to identify the advantages of this cultured
      cell system in predicting in vivo drug absorption after oral administration.
      METHODS: The passive permeability of various drugs through Caco-2 monolayer was
      measured using Ussing-type chambers and compared with that of the isolated rat
      jejunum and colon. The in vivo drug permeability to the intestinal membrane was
      estimated by means of an intestinal perfusion study using the rat jejunum.
      RESULTS: In Caco-2 monolayer, drug permeability increased with increasing drug
      lipophilicity and showed a good linear relationship with the in vivo
      permeability. In contrast, in the isolated jejunum and colon, the permeability of
      high lipophilic drugs was almost constant and, propranolol, a drug with the
      highest lipophilicity, hardly passed through the jejunal membrane in vitro. As a
      result, there was no significant relationship between in vitro and in vivo drug
      permeability in rat jejunum. However, the amount of drugs accumulated in the
      jejunal mucosa increased with increasing drug lipophilicity even under the in
      vitro condition. CONCLUSIONS: The permeation and the accumulation studies
      suggested that the rate-limiting process of in vitro permeation of lipophilic
      drugs through the intestinal membrane differs from that of in vivo drug
      absorption. On the other hand, drug permeation through Caco-2 monolayer, which
      consists of an epithelial cell layer and a supporting filter, is essentially the
      same process as that of in vivo drug absorption. We concluded that the simple
      monolayer structure of a cultured cell system provides a distinct advantage in
      predicting in vivo drug absorption.

PMID- 9144737
TI  - Transport, uptake, and metabolism of the bis(pivaloyloxymethyl)-ester prodrug of
      9-(2-phosphonylmethoxyethyl)adenine in an in vitro cell culture system of the
      intestinal mucosa (Caco-2).
AB  - PURPOSE: To evaluate intestinal transport, uptake and metabolism characteristics
      of the bis(pivaloyloxymethyl)-ester [bis(POM)-ester] of the antiviral agent 9-(2
      phosphonylmethoxyethyl)adenine [PMEA]. METHODS: Intestinal transport, uptake and
      metabolism of bis(POM)-PMEA were studied using an in vitro cell culture system of
      the intestinal mucosa (Caco-2 monolayers). Concentrations of bis(POM)-PMEA and
      its metabolites mono(POM)-PMEA and PMEA were determined using a reversed-phase
      HPLC method. Enzymatic stability of bis(POM)-PMEA was evaluated by incubation
      with purified liver carboxylesterase, homogenates of Caco-2 cells and scraped pig
      small intestinal mucosa. RESULTS: The use of bis(POM)-PMEA as a prodrug of PMEA
      resulted in a significant increase in transport of total PMEA [bis(POM)-PMEA,
      mono(POM)-PMEA and PMEA] across Caco-2 monolayers. While transepithelial
      transport of PMEA (500 microM) was lower than 0.1% during a 3 hr incubation
      period, transport of total PMEA after addition of bis(POM)-PMEA (100 microM)
      amounted to 8.8% over the same incubation period. Only 23% of the amount
      transported appeared as intact bis-ester at the basolateral side, while 33% of
      this amount was free PMEA and 44% was mono(POM)-PMEA, suggesting susceptibility
      of the prodrug to chemical and enzymatic degradation. Uptake studies revealed
      that only negligible amounts of bis(POM)-PMEA (< 0.2%) were present inside the
      cells. Very high intracellular concentrations of PMEA were found (approximately
      1.2 mM, after a 3 hr incubation with 50 microM bis(POM)-PMEA), which suggests
      that PMEA was trapped inside the cells probably due to its negative charge. This
      explains that efflux of PMEA was relatively slow (25% of the intracellular amount
      in 3 hr). Enzymatic degradation of the prodrug by carboxylesterase was confirmed
      by incubation of bis(POM)-PMEA with purified enzyme (Km = 87 microM and Vmax =
      9.5 microM/min). Incubation of bis(POM)-PMEA (10 microM) with cell homogenate of
      Caco-2 monolayers and pig small intestinal mucosa produced similar degradation
      profiles. CONCLUSIONS: The use of the bis(POM)-prodrug significantly enhances the
      intestinal permeability of PMEA. Intracellular trapping of PMEA in the intestinal
      mucosa may result in slow release of PMEA to the circulation after oral
      administration of bis(POM)-PMEA.

PMID- 9144738
TI  - Characterization of fluids from the stomach and proximal jejunum in men and
      women.
AB  - PURPOSE: To chemically characterize the fluids available for drug dissolution in
      the upper gastrointestinal tract during the fasted state in humans, and to
      examine variations and potential gender differences regarding the physico
      chemical properties of these fluids. METHODS: Twenty-four healthy volunteers, 12
      females and 12 males, were intubated, and fluids from the stomach and upper
      jejunum were collected separately. Bulk pH, osmolality, electrolytes and total
      concentrations of bile acids and proteins were assessed. To study intraindividual
      variations, eleven of the individuals were studied on more than one occasion.
      RESULTS: The stomach and upper jejunal fluids varied significantly in all the
      measured entities, except the total concentration of proteins. The
      intraindividual variability was pronounced in some of the individuals, both in
      the stomach and the upper jejunum. We did not, however, observe any gender
      differences. CONCLUSIONS: This study demonstrates the complex nature of the
      fluids available for drug dissolution in the stomach and the upper small
      intestine in humans. The results can be used when designing a more physiological
      in vitro dissolution media representative for the fasted state. When designing
      such a medium, we suggest that gender differences not be taken into account.

PMID- 9144739
TI  - The effect of intestinal bacteria adherence on drug diffusion through solid films
      under stationary conditions.
AB  - PURPOSE: To study the in vitro and in vivo the role of surface bacterial adhesion
      on the diffusion of model drugs at stationary conditions. METHODS: Salicylic acid
      (SA) diffusion through ethyl cellulose (EC) films was measured in vitro in side
      by-side diffusion cells with and without E. coli of intestinal origin. Insulin
      (I) release from paper strips coated or uncoated with pectin films, with or
      without antibiotic treatment, was measured in vivo in conscious rats after cecal
      implantation by comparing blood glucose levels at Tmax of the pharmacodynamic
      effect. RESULTS: During five hours of diffusion studies which were performed
      immediately following incubation of EC films with bacteria, the diffusion rate of
      SA throughout the films was 2.72-fold lower in the presence of bacteria compared
      with the diffusion rate in the control studies conducted without bacteria. The
      mean blood glucose levels dropped in the rat to 40.6 +/- 21.6% of glucose basal
      levels within 2.4 +/- 1.4 h when uncoated I solid carriers were used. Glucose
      levels did not change for pectin-coated dosage forms. After antibiotic treatment
      which prevented the formation of bacterial biofilm on the surface of the I solid
      dosage forms, blood glucose levels dropped to 22.0 +/- 4.7% and 50.9 +/- 20.5% of
      glucose basal levels within 7.4 +/- 2.6 h and 1.8 +/- 0.9 h for pectin uncoated
      or coated dosage forms, respectively. Maximum bacterial adherence occurred at
      stationary conditions (RPM = 0), while at maximum agitation (200 RPM), almost no
      adherence occurred. CONCLUSIONS: (a) Bacterial adherence shows down the diffusion
      rate of SA through EC films; (b) Under stationary conditions bacterial adherence
      may also interfere with drug release from biodegradable (pectin) films; (c)
      Successful functioning of biodegradable colon-specific delivery systems depends
      on agitation and surface friction in the lumen of the colon.

PMID- 9144740
TI  - Evaluation of renal tubular secretion and reabsorption of levofloxacin in rats.
AB  - PURPOSE: Levofloxacin, a quinolone antibacterial drug, is a zwitterion at
      physiological pH. We examined the effect of cationic and anionic drugs on renal
      excretion of levofloxacin by means of in vivo clearance to characterize the
      mechanisms of renal excretion of this drug. METHODS: In vivo clearance was
      studied in male Wistar albino rats. A bolus dose of 2.85 mg/kg of levofloxacin
      was administered, followed by a constant infusion of 7.08 micrograms/min.
      Cimetidine, tetraethylammonium, or p-aminohippurate was administered as a bolus
      and incorporated into the infusion solution. After reaching steady state, urine
      and blood concentrations were measured, and pharmacokinetic parameters were
      calculated. RESULTS: Renal clearance was 2.56 +/- 0.42 ml/min in control, which
      accounted for 34% of the total body clearance. Renal clearance was significantly
      decreased to 0.83 +/- 0.25 ml/min by cimetidine (p < .05), corresponding to 32%
      of the control value. The cationic drug, tetraethyl-ammonium also reduced the
      renal clearance of levofloxacin, but the effect of the anionic drug, p
      aminohippurate, was slight. The clearance ratio of levofloxacin, which was
      calculated by renal clearance divided by the plasma unbound fraction and the
      glomerular filtration rate, was 1.60 +/- 0.38 in the control and it was decreased
      to 0.68 +/- 0.17 and 1.11 +/- 0.22 by cimetidine and tetraethylammonium,
      respectively. CONCLUSIONS: The present results suggest that the renal excretion
      of levofloxacin in rats involves tubular secretion and reabsorption, in addition
      to glomerular filtration, and that tubular secretion is inhibited by cimetidine.

PMID- 9144741
TI  - The effect of RPR 102341 on theophylline metabolism and phenacetin O-deethylase
      activity in human liver microsomes.
AB  - PURPOSE: RPR 102341 is structurally similar to the fluoroquinolone class of
      antibiotics. Because some fluoroquinolones have been shown to inhibit
      theophylline metabolism, concomitant administration may increase plasma levels of
      theophylline resulting in serious adverse effects. The purpose of this study was
      to determine if RPR 102341 affects theophylline metabolism in vitro and, thus,
      predict whether a clinically significant drug interaction is likely to occur. In
      addition, the effect of RPR 102341 on phenacetin O-deethylase activity was
      determined to address the enzymatic basis of a potential drug interaction.
      METHODS: The in vitro theophylline metabolism assay was conducted according to a
      modification of a published procedure. The phenacetin O-deethylase assay was
      conducted according to a modification of a published procedure. RESULTS: The rate
      of conversion of theophylline to 3-methylxanthine in human liver microsomes in
      the presence of 100 microM and 500 microM RPR 102341 was 93.6 and 106 percent of
      the control reactions, respectively. The formation of 1-methylxanthine was 97.6
      and 100 percent of the control, and 1.3-dimethyluric acid formation was 88.9 and
      95.2 percent of control at 100 microM and 500 microM RPR 102341, respectively. In
      agreement, RPR 102341 caused no inhibition of human liver CYP1A2-catalyzed
      phenacetin O-deethylase activity. Finally, no inhibition was observed when RPR
      102341 was incubated with human liver microsomes and an NADPH regenerating system
      prior to the addition of theophylline. CONCLUSIONS: Based on these studies, RPR
      102341 is not expected to cause significant drug interactions with theophylline.

PMID- 9144742
TI  - Hepatic distribution and clearance of antisense oligonucleotides in the isolated
      perfused rat liver.
AB  - PURPOSE: This study was conducted to investigate the impact of backbone
      modifications on the hepatobiliary disposition of oligonucleotides. METHODS: The
      disposition of backbone-modified antisense oligonucleotides [phosphorothioate
      (PS) and methylphosphonate (MP)] of the same base-length and sequence (5'-TAC-GCC
      AAC-AGC-TCC-3'), complementary to the codon 12 activating mutation of Ki-ras, was
      investigated in the isolated perfused rat liver. Livers were perfused for 2 hr:
      perfusate and bile concentrations were analyzed by HPLC. Hepatocellular
      distribution was examined by measuring the amount of radiolabeled PS
      oligonucleotide associated with hepatocytes and Kupffer cells. Protein binding of
      the PS and MP oligonucleotides was determined in rat serum by ultrafiltration.
      RESULTS: MP oligonucleotide perfusate concentrations remained constant during the
      2-hour perfusion. In contrast, PS oligonucleotide was eliminated slowly by the
      isolated perfused liver [CI = 1.05 +/- 0.21 mL/min; extraction ratio = 0.06 +/-
      0.01]. Uptake of PS oligonucleotide by Kupffer cells appeared to exceed uptake by
      hepatocytes, based on standard cell separation techniques as well as confocal
      microscopy. The degree of protein binding in rat serum was greater for the PS
      oligonucleotide (79.9 +/- 2.2%) than for the MP oligonucleotide (53.0 +/- 4.7%).
      CONCLUSIONS: Backbone modifications significantly-influence the hepatic clearance
      of oligonucleotides. Uncharged MP oligonucleotides are not extracted by the
      isolated perfused rat liver, whereas the charged PS oligonucleotide is processed
      more readily.

PMID- 9144743
TI  - Interactions of aldosterone antagonist diuretics with human serum proteins.
AB  - PURPOSE: The purpose of this study was to investigate the binding mechanism of
      aldosterone antagonist diuretics with human serum proteins, human serum albumin
      (HSA) and alpha 1-acid glycoprotein (AGP), as well as to identify the binding
      sites of the drugs on these proteins. METHODS: Binding activities of
      spironolactone (SP) and its pharmacologically active metabolite canrenone (CR) to
      serum and serum protein were examined by ultrafiltration and spectroscopic
      techniques. The data for the binding of these drugs to HSA were analyzed on the
      basis of a theoretical model of simultaneous binding of the ligands. RESULTS: The
      binding percentages of antagonist diuretics SP and CR to human serum proteins
      were 88.0% and 99.2%, respectively, at therapeutic concentrations. SP bound
      strongly only to HSA. In addition, the displacement results found using
      fluorescent probes and ultrafiltration methods demonstrated that SP bound to site
      I, particularly to the warfarin region on HSA, and to the basic binding site on
      AGP, while CR bound to the warfarin region on HSA. CONCLUSIONS: The limited
      results presented here stress the need for caution on coadministration of acidic
      drugs which bind to the warfarin region on HSA and basic drugs which bind to AGP
      with SP and its metabolite CR.

PMID- 9144744
TI  - pH dependent binding of ligands to serum lipoproteins.
AB  - PURPOSE: The binding interactions of binedaline, nicardipine and darodipine with
      lipoproteins (HDL, LDL, VLDL) were examined as a function of pH in order to
      evaluate the role of lipoprotein components and ligand protonation in the binding
      process. METHODS: Binding studies were performed by equilibrium dialysis with
      radiolabeled ligands and differential UV-visible spectroscopy. RESULTS:
      Deprotonated ligands had a markedly higher affinity for lipoproteins than the
      protonated forms, resulting in a concomitant decrease in the pKa of bound
      ligands, i.e., a decrease in the basicity of the ligand in the bound state. The
      UV-visible difference spectra generated upon binding of auramine O to
      lipoproteins also showed that there was a contribution to the binding arising
      from the deprotonation of the ligand. Ligand binding was related to the
      phospholipid and cholesteryl ester content and to a lesser degree to the free
      cholesterol and protein content of lipoproteins, therefore to the surface
      monolayer components of lipoproteins. This relationship was even more accurate
      for the deprotonated, high-affinity, than for the protonated species.
      CONCLUSIONS: It is suggested that among other possible interactions, ligand
      binding to lipoproteins involves proton exchange between the reactants and that
      the high affinity ligand species interact more specifically with the
      phospholipids of the lipoprotein surface monolayer.

PMID- 9144745
TI  - Synthesis and beta-adrenergic activities of R-fluoronaphthyloxypropanolamine.
AB  - PURPOSE: Many biogenic amines where an aromatic proton is substituted with
      fluorine have exhibited pharmacological properties that are dependent on the
      position of fluorine on the aromatic ring. For example, 6-fluoroepinephrine is
      selective for alpha-adrenergic receptors whereas the 2-fluoroisomer is selective
      for beta-receptors. Aryloxypropanolamines are beta-receptor agonists or
      antagonists, depending on the aryl group and its substituents. We therefore
      hypothesized that fluorine substitution on the atomatic ring could lead to
      significant biological effects in this class. A target with fluorine on naphthyl
      group of a known beta-antagonist was chosen for investigation. METHODS: Synthesis
      of the target compound began with fluoronaphthalene and involved introduction of
      4-hydroxy group by Friedel-Crafts acylation followed by Baeyer Villiger
      oxidation. The side chain was introduced stereoselectively using the chiral
      synthon (2R)-glycidyl 3-nitrobenzenesulfonate, a Sharpless epoxidation technique.
      The epoxide was opened with t-butyl amine. HPLC methods were used to characterize
      %ee of the enantiomer. RESULTS: The target compound was synthesized in several
      hundred milligram quantity, and in good yield and high enantiomeric excess,
      showing practicality of the synthetic scheme. It exhibited potent binding
      activities on beta-adrenergic receptors, and was found to be two times selective
      for beta 2-receptors over beta 1. CONCLUSIONS: The current report demonstrates
      that aromatic fluorine substitution on beta-adrenergic ligands can be achieved,
      and that such can be used to obtain binding selectivity between beta receptors.

PMID- 9144746
TI  - Magnetically-responsive polymerized liposomes as potential oral delivery
      vehicles.

PMID- 9144747
TI  - Effect of absorption enhancers on ciliated epithelium: a novel in vivo toxicity
      screening method using rotifers.

PMID- 9144748
TI  - Comparative pharmacokinetics and pharmacodynamics of two recombinant human
      interferon beta-1a (IFN beta-1 a) products administered intramuscularly in
      healthy male and female volunteers.

PMID- 9144750
TI  - A message from Preventive Medicine and your physician.

PMID- 9144749
TI  - Vitamin C intake and cardiovascular disease risk factors in persons with non
      insulin-dependent diabetes mellitus. From the Insulin Resistance Atherosclerosis
      Study and the San Luis Valley Diabetes Study.
AB  - BACKGROUND: Persons with non-insulin-dependent diabetes mellitus (NIDDM) are at
      increased risk for cardiovascular disease, partly due to concomitant worsening of
      traditional risk factors including dyslipidemia and hypertension. Based on
      evidence from small, controlled clinical trials, we hypothesized that increased
      intake of vitamin C would be associated with improved cardiovascular disease
      (CVD) risk factor status among community-dwelling persons with NIDDM. METHODS: In
      separate but parallel statistical analyses, hypotheses were evaluated among
      persons with NIDDM confirmed by WHO criteria from the Insulin Resistance
      Atherosclerosis Study (IRAS, n = 520) and from the San Luis Valley Diabetes Study
      (SLVDS, n = 422). For IRAS, diet and vitamin supplement use was assessed by food
      frequency interview and for SLVDS, by 24-hr dietary recall interview. RESULTS:
      Mean vitamin C intake (mg/day) was 275 for IRAS and 133 for SLVDS, including
      supplements. In cross-sectional regression models from each data set, vitamin C
      intake was not associated with systolic or diastolic blood pressure nor with HDL
      C, LDL-C, or triglycerides (P values > 0.10; adjusted for calories, demographic
      and lifestyle variables, obesity, diabetes duration, and medications). In
      prospective analyses including 285 SLVDS participants, baseline vitamin C intake
      was not related to any of these CVD risk factors measured an average of 4 years
      later nor to change in CVD risk factor status during the follow-up period.
      CONCLUSIONS: We conclude that, across a wide range of intake, vitamin C does not
      appear to be associated with improved CVD risk factor status among community
      dwelling persons with diabetes.

PMID- 9144751
TI  - Reliability of self-reported breast screening information in a survey of lower
      income women.
AB  - BACKGROUND: Self-reported behavior is widely used to estimate the prevalence of
      breast cancer screening and to evaluate programs for promoting screening, but
      detailed studies of reliability have not previously been performed. METHODS:
      Reliability was assessed by comparing responses to questions about screening
      behavior from repeat personal interviews of 382 women age 40 and older living in
      low-income census tracts of two Florida communities. Reliability was assessed
      using Pearson's correlation (r) and kappa (kappa) coefficients. RESULTS:
      Estimated reliabilities were kappa = 0.38 for "ever had clinical breast
      examination," kappa = 0.82 for "ever had mammogram," kappa = 0.65 for "mammogram
      in past year," r = 0.54 for "date of last mammogram," and r = 0.72 for "number of
      mammograms." The dates of last mammogram reported at the two interviews agreed
      within 1 month for 64% of the women, while the dates of last clinical breast
      examination agreed within 1 month for 50% of the women. Reliability of "ever had
      mammogram" was significantly related to demographic variables. CONCLUSIONS: Women
      reliably report ever having mammography, but information about timing and
      frequency has lower reliability. The results have implications for breast
      screening research because measurement error affects the precision of estimates
      and the sample sizes needed to detect program effects.

PMID- 9144752
TI  - Smoking cessation counseling by residents in an outpatient clinic.
AB  - BACKGROUND: Training residents in smoking cessation counseling could be part of
      tobacco control policy. The effect of such an intervention is unknown in Europe.
      This study provides an assessment of smoking cessation counseling practices by
      Swiss residents after an intervention based on behavioral modification. METHOD:
      In a pre-post blind test trial on smoking cessation counseling practices,
      residents' perceptions about their own ability to counsel smoking behavior among
      smoking patients were evaluated for 15 residents trained in general internal
      medicine and in 247 and 155 smoking patients' reports, respectively before and
      after a training intervention targeting residents, based on behavioral theory of
      smoking cessation. RESULTS: Changes in counseling were assessed by interviews
      with patients. After the intervention, residents asked about smoking habits (77
      vs 68%), advised to quit (43 vs 28%), provided counseling for cessation (25 vs
      10%), gave self-help materials (7 vs 1%), and arranged follow-up visits (5 vs 1%)
      more often than before. Residents' self-perception of confidence (5.4 vs 4.6/10)
      and effectiveness (5.3 vs 4.0/10) in counseling also increased after the
      intervention. After adjusting for daily cigarette consumption and smoking
      duration, the likelihood of attempting to quit smoking at either 6 or 12 months
      was increased in the group of patients attended after the intervention (odds
      ratio 1.52, 95% confidence intervals 1.07-2.48). However, the likelihood of
      quitting smoking was not increased among these patients (odds ratio 1.07, 95% CI
      0.96-1.14). CONCLUSIONS: Short-term smoking cessation counseling by residents was
      substantially improved by the intervention. Smokers attended after the
      intervention were more likely to attempt to quit smoking, but not to have quit at
      6- or 12-month follow-up.

PMID- 9144753
TI  - Mediators of change in physical activity following an intervention in primary
      care: PACE.
AB  - BACKGROUND: The current study evaluated the construct validity of a physical
      activity intervention in primary care by testing whether the intervention changed
      hypothesized mediators and whether changes in the mediators were associated with
      behavior change. METHODS: Matched physician offices were nonrandomly assigned to
      intervention or control. Apparently healthy, sedentary, adult patients (N = 255)
      were recruited from physician offices. The intervention was brief, behaviorally
      based counseling by physicians, plus a telephone follow-up 2 weeks later.
      Assessments of physical activity and mediators were collected at baseline and at
      4- to 6-week follow-up. Hypothesized mediators were processes of change, self
      efficacy, and social support for exercise. RESULTS: Patients who were counseled
      improved significantly more than those in the control group on behavioral and
      cognitive processes of change. Other changes in mediators were nonsignificant.
      Behavioral processes of change and self-efficacy made significant contributions
      to the multiple regression model explaining self-report and objective measures of
      physical activity. CONCLUSIONS: The intervention affected some of the targeted
      mediators of physical activity change. Two of three mediator variables were
      associated with changes in physical activity regardless of experimental condition
      and other variables. The construct validity of the intervention was partially
      supported.

PMID- 9144754
TI  - Distribution, determinants, and prognostic value of gamma-glutamyltransferase for
      all-cause mortality in a cohort of construction workers from southern Germany.
AB  - BACKGROUND: Serum gamma-glutamyltransferase (GGT) is commonly measured as a
      marker of hepatobiliary disorders in clinical practice, but little is known about
      its distribution and prognostic value for all-cause mortality. METHODS:
      Distribution and determinants of serum GGT levels were assessed among 8,043
      construction workers ages 25-64 who underwent occupational health examinations in
      six centers in Southern Germany from 1986 to 1988. Study participants were
      followed for all-cause mortality until 1994. RESULTS: Serum GGT levels were
      considerably higher in this cohort than among male employees examined in a
      national survey conducted during the same period. The factors most strongly
      related to serum GGT were self-reported alcohol consumption, body mass index,
      diabetes, and hypertension, but relations of GGT levels were also found with
      nationality, occupation, and smoking. There was a strong dose-response relation
      between serum GGT levels and all-cause mortality (P value for trend < 0.001).
      Compared with men with GGT levels below 15 U/liter (measured at 25 degrees C),
      relative risks (95% CI) were 1.46 (0.86-2.49), 1.78 (1.08-2.94), 2.09 (1.26
      3.45), and 3.44 (2.20-5.38) for men with GGT levels of 15-19, 20-29, 30-49, and >
      or = 50 U/liter, respectively. This relation was reduced but not eliminated by
      control for body mass index, diabetes, hypertension, alcohol consumption, and
      other covariates in multivariable analysis. CONCLUSION: Serum GGT is a strong
      risk indicator of all-cause mortality.

PMID- 9144755
TI  - Community-based surveillance of cardiovascular risk factors in Geneva: methods,
      resulting distributions, and comparisons with other populations.
AB  - OBJECTIVES: This paper presents the results of an ongoing community-based
      surveillance program of cardiovascular risk factors in Geneva, Switzerland, using
      percentiles with their associated 95% confidence intervals and compares the
      Genevan results with published data from international surveys reporting
      percentiles. METHODS: A random survey of adults ages 35 to 74 years was conducted
      from 1993 to 1994. Confidence intervals for percentiles based on parametric and
      non-parametric methods are given. RESULTS: The distribution of total cholesterol
      was shifted upward with increasing age. The median reached a maximum at 55-64
      years among men (5.7 mmol/L) and at 65-74 years among women (5.9 mmol/L), and
      remained relatively stable thereafter. In both genders, systolic and, less so,
      diastolic blood pressure increased progressively with advancing age. The median
      daily energy intake among men declined from 2,390 kcal at age 35-44 years to
      2,169 kcal at age 65-74 years, while among women it remained stable at about
      1,900 kcal. In both males and females, the relative intake of saturated fat was
      stable throughout life (14 to 13%). The median body mass index (BMI) was about 25
      kg/m2 across all age groups among men, but increased with age among women, with a
      peak of 23.6 kg/m2 occurring at ages 65-74 years. Compared with U.S. and western
      European surveys, Genevan men and women had lower total plasma cholesterol and
      Genevan women tended to have lower BMIs. CONCLUSIONS: Percentiles with their
      associated precision appear particularly well suited for international comparison
      of surveillance data. They could be used in the future to monitor shifts in
      distributions resulting from mass prevention strategies.

PMID- 9144756
TI  - Improving breast self-examination compliance: a Southwest Oncology Group
      randomized trial of three interventions.
AB  - BACKGROUND: Only 20-40% of U.S. women conduct breast self-examination (BSE). This
      Southwest Oncology Group experimental study compared the impact of three
      interventions on BSE compliance. METHODS: Subjects were randomly assigned to one
      of three arms: (1) physician message; (2) physician message and BSE class; or (3)
      physician message, BSE class, and reinforcement (phone and postcard). Compliance
      (frequency and accuracy) was measured by interview at intake and at 6 months and
      by phone contact at 1 year. Logistic and multiple regression were employed.
      RESULTS: This analysis included 2,233 subjects from six institutions. At 1 year
      the percentages of women doing BSE were 59, 62, and 78% for Arms 1-3,
      respectively; gains over intake frequency (27% average) were significant within
      each arm (P < or = 0.0001). At both 6 months and 1 year the differences between
      Arm 1 and Arm 2 average accuracy scores and the differences between Arm 2 and Arm
      3 in the percentage of women doing BSE were significant (P < or = 0.0001).
      Findings within institutions were consistent with the overall findings.
      CONCLUSIONS: The addition of a BSE class increased accuracy over physician
      message alone; physician message, BSE class, and reinforcement gave the highest
      percentage of women doing BSE.

PMID- 9144757
TI  - Work-related interventions during office visits to occupational health
      physicians.
AB  - BACKGROUND: Systematically applied work-related interventions during visits to
      occupational health (OH) physicians support the preventive and health promotive
      goals of OH. The proportion of the visits including a work-related intervention
      was analyzed according to patient, health problem, and physician determinants in
      a sample of visits to OH physicians in Finland. METHODS: A cross-sectional study
      was carried out among 55 Occupational Health Services (OHS) units. Office
      encounters with 4,404 male and 5,373 female employed patients ages 18-64 years,
      recorded by 114 OHS physicians, were analyzed. RESULTS: Altogether 856 (8.8%)
      encounters included a work-related intervention. The work-related interventions
      were distributed across all the main disease categories, the majority of which
      were musculoskeletal diseases. Of the patient determinants, occupational group
      (the residual group of non-white-collar or non-blue-collar workers) associated
      positively with a work-related intervention, while age or gender did not. The
      physician's female gender and experience associated positively with work-related
      interventions. Work-related interventions took place more often in integrated and
      joint model OHS than in municipal health care centers and private medical
      centers. CONCLUSIONS: Work-related interventions are used by OH physicians for
      diverse health problems. More research is needed to better understand the reasons
      for the observed differences in work-related interventions. Also, research is
      needed to evaluate the efficiency of such interventions.

PMID- 9144758
TI  - Patients' perceptions of their physician's role in smoking cessation by age and
      readiness to stop smoking.
AB  - BACKGROUND: Patients' perceptions of their physician's role in smoking cessation,
      using the 4As protocol (asking, advising, assisting, and arranging), were
      assessed with a focus on associations with age (18-29, 30-49, and > or = 50) and
      stage of readiness to stop smoking (precontemplation, contemplation, and
      preparation). METHODS: Self-administered questionnaires were completed by 524
      smokers presenting for regularly scheduled appointments at six clinics of an HMO
      in the Chicago metropolitan area. RESULTS: Almost all patients said their
      physician should ask about their smoking status and advise them to quit. About
      half said their physician should assist them with quitting, and about two-thirds
      said their physician should follow up (arrange) on their smoking behavior.
      Bivariate associations were found for endorsement of the 4As with both age and
      stage. Multiple logistic regressions found age was the most consistent and
      strongest correlate of 4As endorsement, with younger smokers more likely than
      those age 50 or older to endorse the 4As protocol. CONCLUSIONS: A proactive
      health promotion orientation should be encouraged among physicians. Patients
      should be screened for stage of readiness to stop smoking so that health-care
      providers can emphasize aspects of the 4As protocol that are most appropriate for
      each patient. Age-tailored smoking cessation strategies should be employed within
      stages of readiness to stop smoking.

PMID- 9144759
TI  - Are physicians less likely to recommend preventive services to low-SES patients?
AB  - BACKGROUND: Do low-SES adult patients visiting private primary care clinics
      differ from higher SES adult patients in their need for eight preventive services
      or in receiving either a recommendation for or the needed services? METHODS:
      Randomly identified adult patients were surveyed within 2 weeks of a visit to 22
      clinics in the Minneapolis-St. Paul area. Questions assessed patient recollection
      of the latest receipt of eight services and whether needed services had been
      recommended during the visit or received then soon after. RESULTS: Of those
      surveyed, 4,245 patients (1,650 low SES) responded (84.3%), showing that low SES
      patients were less likely to be up to date for cholesterol measurement, Pap
      smear, mammography, breast exam, and flu or pneumonia shots (P < 0.004), but not
      for blood pressure measurement. Low-SES patients needing services received
      recommendations to have them and actually received them at the same rate as
      higher SES patients. CONCLUSIONS: The 22 primary care clinics studied appear to
      be recommending and providing needed preventive services to visiting patients at
      the same rate regardless of income or insurance status. The reasons for
      differences in prevention status by SES are complex but the low proportion of all
      patients receiving recommendations for needed services suggests the need to take
      advantage of all visits for updating prevention needs.

PMID- 9144760
TI  - Household smoking restrictions and adolescents' exposure to environmental tobacco
      smoke.
AB  - BACKGROUND: Reducing adolescents' exposure to environmental tobacco smoke (ETS)
      is an important public health goal. This paper identifies the linkage between
      young people's exposure at home and household smoking restrictions, and suggests
      the promotion of such restrictions as a strategy to reduce health risks. METHODS:
      Data are from the 1993 Massachusetts Tobacco Survey, a telephone survey of 1,606
      adolescents. RESULTS: Seventy-eight percent of adolescents reported exposure to
      ETS during the preceding week. Reported hours of exposure at home were associated
      with the number of adult smokers in the household (P < 0.001). Fifty-three
      percent of teens who lived with smokers reported no smoking restrictions for
      family members, 22% reported designated smoking areas, and 25% reported smoking
      bans. Among those households, smoking restrictions for family members were
      associated with significant reductions in mean hours of ETS exposure reported: no
      restrictions were associated with 33.2 hr of exposure during the prior week,
      designated smoking areas--12.7 hr, and household smoking bans--2.4 hr.
      Restrictions on visitor smoking were associated with significant reductions in
      home ETS exposure for teens who lived with nonsmokers, but had no independent
      effect among teens who lived with smokers. CONCLUSIONS: Health risks experienced
      by adolescents living with adult smokers can be substantially reduced by
      household smoking restrictions.

PMID- 9144761
TI  - Summer sun exposure: knowledge, attitudes, and behaviors of Midwest adolescents.
AB  - BACKGROUND: Extensive print, radio, and television coverage about the dangers of
      sun exposure and benefits of sun protection occurred over the past decade.
      Illinois teen knowledge and attitudes about sun exposure/protection, sun
      exposure/protection behavior, and information sources were determined by a summer
      telephone survey. METHODS: Telephone interviews with 658 teenagers between ages
      11 and 19 included African-American, Asian, Hispanic, Native American, and white
      teenagers. RESULTS: Teens knew that too much sun was harmful as it caused skin
      cancer and sunburn. Sunburn was mentioned more often by those with skin types
      that burned easily and tanned poorly (I,II) (P < 0.001), was better known to
      girls than to boys (P < 0.001), and was recognized more by those with higher
      socioeconomic status (P < 0.001) but was not associated with age. Widely held sun
      exposure attitudes were socializing with friends and feeling better when
      outdoors. On weekdays, boys averaged 5.3 hr (SD, 1.65 hr) outside compared with
      3.9 hr (SD, 0.75 hr) for girls (P < 0.001). Teenage boys were more likely to
      obtain occupational sun exposure, and girls sunbathed. Subjects with skin types I
      and II reported an average of 3.3 sunburns in the past year. During unprotected
      sun exposure, extensive numbers of teens with moderate-risk skin type experienced
      at least 1 sunburn per year. Indoor tanning use was more prevalent among older
      girls and those with skin types I and II. Sunscreen use was associated with water
      recreational activities (swimming, water sports, and going to the beach) by girls
      slightly more than by boys (P < 0.001). Hat-wearing was more common among boys
      than among girls. CONCLUSIONS: Teen knowledge that excessive sun exposure causes
      skin cancer and sunburns and that wearing sunscreens and hats were sun-protective
      methods did not enable sun protection that prevented burning. This is
      particularly troublesome because severe sunburns in youth are associated with an
      increased risk of melanoma. Existing teen sunscreen use could be broadened by
      educating teens to use adequate quantities of sunscreen prior to daily sun
      exposure to prevent painful burns. Messages to teens that emphasize the short
      term consequence of painful sunburns because of inadequate protection during
      outdoor occupational and non-water-related recreational exposure would increase
      the relevance of the message and may enable behavioral change. Parents and
      physicians need to be included in messages that are directed to teens and to
      become part of their education. Parents could ensure an adequate sunscreen supply
      for daily use by the family, encourage teens not to deliberately tan, and serve
      as role models for the use of protective clothing.

PMID- 9144762
TI  - Analysis of a multicomponent smoking cessation project: what worked and why.
AB  - BACKGROUND: Health promotion interventions often contain several, conceptually
      diverse elements. As a result, it is often difficult to determine why
      interventions succeed or fail as well as which components should be retained or
      eliminated. One method to examine the effectiveness of individual intervention
      elements is process analysis. METHODS: Kick It! is a multicomponent smoking
      cessation intervention developed for lower socioeconomic African Americans. The
      intervention includes several components, including a 24-page printed cessation
      manual, a staged-cessation video, a quit contract, two "Quit and Win" contests,
      and a single telephone booster call. Using data from a randomized intervention
      trial designed to test the efficacy of the Kick It! intervention, this article
      examines the use, impact, and interaction of the intervention's subcomponents as
      well as possible mediating variables related to successful quitting among
      intervention participants (n = 650). RESULTS: In univariate as well as
      multivariate analyses adjusting for age and stage of change, two of the five
      elements, watching the video and entering a Quit and Win contest, were
      significantly associated with 6-month point prevalence abstinence. Submitting a
      quit contract and receiving the booster call were significantly associated with
      quitting in univariate analyses, while reading the Kick It! guide was not
      significantly associated with quitting in either analysis. CONCLUSIONS: Despite
      the positive effects observed for individual elements, quitting was not
      significantly greater among intervention relative to comparison subjects. The
      primary reason for this appears to be the overall lack of intervention use.
      Additional research examining strategies to increase use of the Kick It!
      intervention components as well as the optimal sequencing and combination of
      components may be warranted.

PMID- 9144763
TI  - Training physicians to conduct physical activity counseling.
AB  - BACKGROUND: In accordance with the U.S. Preventive Services Task Force
      recommendations, the current pilot study tests the feasibility and efficacy of a
      physician-delivered physical activity counseling intervention. METHODS: A
      sequential comparison group design was used to examine change in self-reported
      physical activity between experimental (counseling and self-help materials) and
      control (usual care) patients at base-line and 6 weeks after the initial office
      visit. Patients in both groups were contacted by telephone 2 weeks after their
      office visit and asked about the physical activity counseling at their most
      recent physician visit. Experimental patients also received a follow-up
      appointment to discuss physical activity with their physician 4 weeks after their
      initial visit. RESULTS: Counseling was feasible for physicians to do and produced
      short-term increases in physical activity levels. Both groups increased their
      physical activity, but the increase in physical activity was greater for patients
      who reported receiving a greater number of counseling messages. CONCLUSIONS:
      Physician-delivered physical activity interventions may be an effective way to
      achieve wide-spread improvements in the physical activity of middle-aged and
      older adults.

PMID- 9144764
TI  - Long-term responses of higher and lower risk youths to smoking prevention
      interventions.
AB  - BACKGROUND: Adolescents at risk for cigarette smoking are difficult to reach with
      conventional interventions but have substantial exposure to the mass media. This
      study is the first to show that smoking prevention messages presented through the
      mass media can have large and durable effects on higher risk adolescents.
      METHODS: Students in two communities received media and school interventions
      beginning in grades 5-7; those in matched comparison communities received school
      interventions. Media interventions were targeted to higher risk youths. School
      surveys were conducted before and after the interventions, in grades 4-6 and
      grades 8-10. Two years after interventions ended, when participants were in
      grades 10-12, school and telephone surveys were conducted to assess smoking
      status. Survey participants (n = 2,860) were classified at baseline as having
      higher or lower risk for becoming a smoker. RESULTS: Smoking prevalence within
      the higher risk sample was significantly lower for those receiving media-school
      interventions than for those receiving school interventions only (odds ratio =
      0.71). Effects on the lower risk sample were similar in magnitude but marginally
      significant. CONCLUSIONS: Mass media and school interventions achieved lower
      smoking rates among higher risk youngsters 2 years following completion of the
      interventions. This strategy represents a uniquely effective method for
      communicating with a high-priority group.

PMID- 9144765
TI  - Energy intake and monounsaturated fat in relation to bone mineral density among
      women and men in Greece.
AB  - BACKGROUND: Several variables have been established as risk factors for
      osteoporosis: it is more common among women and the gender difference increases
      with age and with years since menopause. Estrogens, androgens, physical activity,
      and body mass index have been previously shown to be positively associated with
      bone mineral density and inversely with risk for fractures. METHODS: To assess
      the effect on bone mineral content of energy-generating nutrients, healthy men (n
      = 36) and women (n = 118) ages 25-69 years were interviewed among visitors and
      staff of the University of Athens Department of Medical Physics. Bone mineral
      density (BMD) was measured by single photon absorptiometry. RESULTS: Demographic
      and lifestyle variables were not significantly related to BMD in this study,
      although the patterns were consistent with those previously reported by other
      investigators. Total energy intake, which also reflects energy expenditure
      through physical activity, was positively associated with BMD among both men (P =
      0.003) and women (P = 0.04). After adjustment for nonnutritional variables and
      energy intake, monounsaturated fat, which in the Greek population is mostly
      derived from olive oil, was associated with BMD. The association was positive
      among both men (P = 0.01) and women (P = 0.03). There was evidence for an inverse
      association between carbohydrate intake and BMD, but the association was
      significant only with respect to mono- and disaccharides. CONCLUSIONS: In this
      population, consumption of monounsaturated fat and physical activity were
      predictive of bone mineral density, but larger studies are needed.

PMID- 9144768
TI  - Characterization of the allosteric binding pocket of human liver fructose-1,6
      bisphosphatase by protein crystallography and inhibitor activity studies.
AB  - The structures of three complexes of human fructose-1,6-bisphosphatase (FB) with
      the allosteric inhibitor AMP and two AMP analogues have been determined and all
      fully refined. The data used for structure determination were collected at
      cryogenic temperature (110 K), and with the use of synchrotron radiation. The
      structures reveal a common mode of binding for AMP and formycine monophosphate
      (FMP). 5-Amino-4-carboxamido-1 beta-D-5-phosphate-ribofuranosyl-1H-imidazole
      (AICAR-P) shows an unexpected mode of binding to FB, different from that of the
      other two ligands. The imidazole ring of AICAR-P is rotated 180 degrees compared
      to the AMP and FMP bases. This rotation results in a slightly different hydrogen
      bonding pattern and minor changes in the water structure in the binding pocket.
      Common features of binding are seen for the ribose and phosphate moieties of all
      three compounds. Although binding in a different mode, AICAR-P is still capable
      of making all the important interactions with the residues building the
      allosteric binding pocket. The IC50 values of AMP, FMP, and AICAR-P were
      determined to be 1.7, 1.4, and 20.9 microM, respectively. Thus, the approximately
      10 times lower potency of AICAR-P is difficult to explain solely from the
      variations observed in the binding pocket. Only one water molecule in the
      allosteric binding pocket was found to be conserved in all four subunits in all
      three structures. This water molecule coordinates to a phosphate oxygen atom and
      the N7 atom of the AMP molecule, and to similarly situated atoms in the FMP and
      AICAR-P complexes. This implies an important role of the conserved water molecule
      in binding of the ligand.

PMID- 9144767
TI  - Homology modeling using simulated annealing of restrained molecular dynamics and
      conformational search calculations with CONGEN: application in predicting the
      three-dimensional structure of murine homeodomain Msx-1.
AB  - We have developed an automatic approach for homology modeling using restrained
      molecular dynamics and simulated annealing procedures, together with
      conformational search algorithms available in the molecular mechanics program
      CONGEN (Bruccoleri RE, Karplus M, 1987, Biopolymers 26:137-168). The accuracy of
      the method is validated by "predicting" structures of two homeodomain proteins
      with known three-dimensional structures, and then applied to predict the three
      dimensional structure of the homeodomain of the murine Msx-1 transcription
      factor. Regions of the unknown protein structure that are highly homologous to
      the known template structure are constrained by "homology distance constraints,"
      whereas the conformations of nonhomologous regions of the unknown protein are
      defined only by the potential energy function. A full energy function (excluding
      explicit solvent) is employed to ensure that the calculated structures have good
      conformational energies and are physically reasonable. As in NMR structure
      determinations, information on the consistency of the structure prediction is
      obtained by superposition of the resulting family of protein structures. In this
      paper, our homology modeling algorithm is described and compared with related
      homology modeling methods using spatial constraints derived from the structures
      of homologous proteins. The software is then used to predict the DNA-bound
      structures of three homeodomain proteins from the X-ray crystal structure of the
      engrailed homeodomain protein (Kissinger CR et al., 1990, Cell 63:579-590). The
      resulting backbone and side-chain conformations of the modeled yeast Mat alpha 2
      and D. melanogaster Antennapedia homeodomains are excellent matches to the
      corresponding published X-ray crystal (Wolberger C et al., 1991, Cell 67:517-528)
      and NMR (Billeter M et al., 1993, J Mol Biol 234:1084-1097) structures,
      respectively. Examination of these structures of Msx-1 reveals a network of
      highly conserved surface salt bridges that are proposed to play a role in
      regulating protein-protein interactions of homeodomains in transcription
      complexes.

PMID- 9144769
TI  - Predicted structure of the extracellular region of ligand-gated ion-channel
      receptors shows SH2-like and SH3-like domains forming the ligand-binding site.
AB  - Fast synaptic neurotransmission is mediated by ligand-gated ion-channel (LGIC)
      receptors, which include receptors for acetylcholine, serotonin, GABA, glycine,
      and glutamate. LGICs are pentamers with extracellular ligand-binding domains and
      form integral membrane ion channels that are selective for cations (acetylcholine
      and serotonin 5HT3 receptors) or anions (GABAA and glycine receptors and the
      invertebrate glutamate-binding chloride channel). They form a protein superfamily
      with no sequence similarity to any protein of known structure. Using a 1D-3D
      structure mapping approach, we have modeled the extracellular ligand-binding
      domain based on a significant match with the SH2 and SH3 domains of the biotin
      repressor structure. Refinement of the model based on knowledge of the large
      family of SH2 and SH3 structures, sequence alignments, and use of structure
      templates for loop building, allows the prediction of both monomer and pentamer
      models. These are consistent with medium-resolution electron microscopy
      structures and with experimental structure/function data from ligand-binding,
      antibody-binding, mutagenesis, protein-labeling and subunit-linking studies, and
      glycosylation sites. Also, the predicted polarity of the channel pore calculated
      from electrostatic potential maps of pentamer models of superfamily members is
      consistent with known ion selectivities. Using the glycine receptor alpha 1
      subunit, which forms homopentamers, the monomeric and pentameric models define
      the agonist and antagonist (strychnine) binding sites to a deep crevice formed by
      an extended loop, which includes the invariant disulfide bridge, between the SH2
      and SH3 domains. A detailed binding site for strychnine is reported that is in
      strong agreement with known structure/function data. A site for interaction of
      the extracellular ligand-binding domain with the activation of the M2
      transmembrane helix is also suggested.

PMID- 9144770
TI  - Template-based docking of a prolactin receptor proline-rich motif octapeptide to
      FKBP12: implications for cytokine receptor signaling.
AB  - A conserved proline-rich motif (PRM) in the cytoplasmic domain of cytokine
      receptors has been suggested to be a signaling switch regulated by the action of
      the FK506 binding protein (FKBP) family of peptidylprolyl isomerases (O'Neal KD,
      Yu-Lee LY, Shearer WT, 1995, Ann NY Acad Sci 766:282-284). We have docked the
      prolactin receptor PRM (Ile1-Phe2-Pro3-Pro4-Val5-Pro6-Gly7-Pro8) to the ligand
      binding site of FKBP12. The procedure involved conformational search restricted
      by NMR restraints (O'Neal KD et al., 1996, Biochem J 315:833-844), energy
      minimization of the octapeptide conformers so obtained, template-based docking of
      a selected conformer to FKBP12, and energy refinement of the resulting complex.
      The template used was the crystal structure of a cyclic FK506-peptide hybrid
      bound to FKBP12. Val5-Pro6 of the PRM was taken to be the biologically relevant
      Xaa-Pro bond. The docked conformer is stabilized by two intramolecular hydrogen
      bonds, N7H7-->O4 and N2H2-->O8, and two intermolecular ones, Ile56; N-H-->O =
      C:Pro6 and Tyr82:O-H-->O = C:Gly7. This conformer features a Type I beta-turn and
      has extensive hydrophobic contacts with the FKBP12 binding surface. The observed
      interactions support the hypothesis that FKBP12 catalyzes cis-trans isomerization
      in the PRM when it is part of the longer cytoplasmic domain of a cytokine
      receptor, and suggest a significant role for the PRM in signal transduction.

PMID- 9144771
TI  - Three-dimensional structures of glycolate oxidase with bound active-site
      inhibitors.
AB  - A key step in plant photorespiration, the oxidation of glycolate to glyoxylate,
      is carried out by the peroxisomal flavoprotein glycolate oxidase (EC 1.1.3.15).
      The three-dimensional structure of this alpha/beta barrel protein has been
      refined to 2 A resolution (Lindqvist Y. 1989. J Mol Biol 209:151-166). FMN
      dependent glycolate oxidase is a member of the family of alpha-hydroxy acid
      oxidases. Here we describe the crystallization and structure determination of two
      inhibitor complexes of the enzyme, TKP (3-Decyl-2,5-dioxo-4-hydroxy-3-pyrroline)
      and TACA (4-Carboxy-5-(1-pentyl)hexylsulfanyl-1,2,3-triazole). The structure of
      the TACA complex has been refined to 2.6 A resolution and the TKP complex, solved
      with molecular replacement, to 2.2 A resolution. The Rfree for the TACA and TKP
      complexes are 24.2 and 25.1%, respectively. The overall structures are very
      similar to the unliganded holoenzyme, but a closer examination of the active site
      reveals differences in the positioning of the flavin isoalloxazine ring and a
      displaced flexible loop in the TKP complex. The two inhibitors differ in binding
      mode and hydrophobic interactions, and these differences are reflected by the
      very different Ki values for the inhibitors, 16 nM for TACA and 4.8 microM for
      TKP. Implications of the structures of these enzyme-inhibitor complexes for the
      model for substrate binding and catalysis proposed from the holo-enzyme structure
      are discussed.

PMID- 9144772
TI  - Identification of a novel bond between a histidine and the essential tyrosine in
      catalase HPII of Escherichia coli.
AB  - A bond between the N delta of the imidazole ring of His 392 and the C beta of the
      essential Tyr 415 has been found in the refined crystal structure at 1.9 A
      resolution of catalase HPII of Escherichia coli. This novel type of covalent
      linkage is clearly defined in the electron density map of HPII and is confirmed
      by matrix-assisted laser desorption/ionization mass spectrometry analysis of
      tryptic digest mixtures. The geometry of the bond is compatible with both the sp3
      hybridization of the C beta atom and the planarity of the imidazole ring. Two
      mutated variants of HPII active site residues, H128N and N201H, do not contain
      the His 392-Tyr 415 bond, and their crystal structures show that the imidazole
      ring of His 392 was rotated, in both cases, by 80 degrees relative to its
      position in HPII. These mutant forms of HPII are catalytically inactive and do
      not convert heme b to heme d, suggesting a relationship between the self
      catalyzed heme conversion reaction and the formation of the His-Tyr linkage. A
      model coupling the two processes and involving the reaction of one molecule of
      H2O2 on the proximal side of the heme with compound 1 is proposed.

PMID- 9144773
TI  - Solvation effects are responsible for the reduced inhibitor affinity of some HIV
      1 PR mutants.
AB  - The formulation of HIV-1 PR inhibitors as anti-viral drugs has been hindered by
      the appearance of protease strains that present drug resistance to these
      compounds. The mechanism by which the HIV-1 PR mutants lower their affinity for
      the inhibitor is not yet fully understood. We have applied a modified Poisson
      Boltzmann method to the evaluation of the molecular interactions that contribute
      to the lowering of the inhibitor affinity to some polar mutants at position 82.
      These strains present drug resistance behavior and hence are ideally suited for
      these studies. Our results indicate that the reduction in binding affinity is due
      to the solvation effects that penalize the binding to the more polar mutants. The
      inhibitor binding ranking of the different mutants can be explained from the
      analysis of the different components of our free energy scoring function.

PMID- 9144766
TI  - Interleukin-6: structure-function relationships.
AB  - Interleukin-6 (IL-6) is a multifunctional cytokine that plays a central role in
      host defense due to its wide range of immune and hematopoietic activities and its
      potent ability to induce the acute phase response. Overexpression of IL-6 has
      been implicated in the pathology of a number of diseases including multiple
      myeloma, rheumatoid arthritis, Castleman's disease, psoriasis, and post
      menopausal osteoporosis. Hence, selective antagonists of IL-6 action may offer
      therapeutic benefits. IL-6 is a member of the family of cytokines that includes
      interleukin-11, leukemia inhibitory factor, oncostatin M, cardiotrophin-1, and
      ciliary neurotrophic factor. Like the other members of this family, IL-6 induces
      growth or differentiation via a receptor-system that involves a specific receptor
      and the use of a shared signaling subunit, gp130. Identification of the regions
      of IL-6 that are involved in the interactions with the IL-6 receptor, and gp130
      is an important first step in the rational manipulation of the effects of this
      cytokine for therapeutic benefit. In this review, we focus on the sites on IL-6
      which interact with its low-affinity specific receptor, the IL-6 receptor, and
      the high-affinity converter gp130. A tentative model for the IL-6 hexameric
      receptor ligand complex is presented and discussed with respect to the mechanism
      of action of the other members of the IL-6 family of cytokines.

PMID- 9144774
TI  - The role of divalent cations in structure and function of murine adenosine
      deaminase.
AB  - For murine adenosine deaminase, we have determined that a single zinc or cobalt
      cofactor bound in a high affinity site is required for catalytic function while
      metal ions bound at an additional site(s) inhibit the enzyme. A catalytically
      inactive apoenzyme of murine adenosine deaminase was produced by dialysis in the
      presence of specific zinc chelators in an acidic buffer. This represents the
      first production of the apoenzyme and demonstrates a rigorous method for removing
      the occult cofactor. Restoration to the holoenzyme is achieved with
      stoichiometric amounts of either Zn2+ or Co2+ yielding at least 95% of initial
      activity. Far UV CD and fluorescence spectra are the same for both the apo- and
      holoenzyme, providing evidence that removal of the cofactor does not alter
      secondary or tertiary structure. The substrate binding site remains functional as
      determined by similar quenching measured by tryptophan fluorescence of apo- or
      holoenzyme upon mixing with the transition state analog, deoxycoformycin. Excess
      levels of adenosine or N6- methyladenosine incubated with the apoenzyme prior to
      the addition of metal prevent restoration, suggesting that the cofactor adds
      through the substrate binding cleft. The cations Ca2+, Cd2+, Cr2+, Cu+, Cu2+,
      Mn2+, Fe2+, Fe3+, Pb2+, or Mg2+ did not restore adenosine deaminase activity to
      the apoenzyme. Mn2+, Cu2+, and Zn2+ were found to be competitive inhibitors of
      the holoenzyme with respect to substrate and Cd2+ and Co2+ were noncompetitive
      inhibitors. Weak inhibition (Ki > or = 1000 microM) was noted for Ca2+, Fe2+, and
      Fe3+.

PMID- 9144775
TI  - Design, synthesis, expression, and characterization of the genes for mouse Fc
      gamma RIIb1 and Fc gamma RIIb2 cytoplasmic regions.
AB  - The cytoplasmic regions of the mouse low-affinity Fc gamma RII isoforms, mFc
      gamma RIIb1, and mFc gamma RIIb2, play a key role in signal transduction by
      mediating different cellular functions. mFc gamma RIIb1 has a 94-residue
      cytoplasmic region, whereas mFc gamma RIIb2 has a 47-residue cytoplasmic region.
      Genes encoding the cytoplasmic regions of mFc gamma RIIb1 (b1-94) and mFc gamma
      RIIb2 (b2-47) were designed, synthesized, and expressed as fusion proteins in
      Escherichia coli. A sequence-specific protease, thrombin, was used to release the
      b1-94 peptide, which was purified by using HPLC. The b2-47 peptide was
      synthesized chemically. CD spectropolarimetry was employed to examine the
      secondary structures of b1-94 and b2-47. These studies were conducted in aqueous
      solution, in mixtures of water and trifluoroethanol or methanol, and as a
      function of temperature. The results indicate that the b1-94 and b2-47 structures
      are sensitive functions of the solvent environment, and that nonaqueous solvents
      induce significant alpha-helical structure.

PMID- 9144776
TI  - Hsc66 and Hsc20, a new heat shock cognate molecular chaperone system from
      Escherichia coli.
AB  - The hscA and hscB genes of Escherichia coli encode novel chaperone and co
      chaperone proteins, designated Hsc66 and Hsc20, respectively. We have
      overproduced and purified Hsc66 and Hsc20 in high yield in E. coli and describe
      their initial characterization including absorbance, fluorescence, and circular
      dichroism spectra. Immunoblot analyses of E. coli cultures using antisera to
      Hsc66 and Hsc20 raised in rabbits establish that Hsc66 and Hsc20 are
      constitutively expressed at levels corresponding to cell concentration
      approximately 20 microM and approximately 10 microM, respectively. The levels do
      not change appreciably following heat shock (44 degrees C), but a small increase
      in Hsc20 is observed following a shift to 10 degrees C. Purified Hsc66 exhibits a
      low intrinsic ATPase activity (approximately 0.6 min-1 at 37 degrees C), and
      Hsc20 was found to stimulate this activity up to 3.8-fold with half-maximal
      stimulation at a concentration approximately 5 microM. These findings suggest
      that Hsc66 and Hsc20 comprise a molecular chaperone system similar to the
      prokaryotic DnaK/DnaJ and eukaryotic hsp70/hsp40 systems. Sequence differences
      between Hsc66 and Hsc20 compared to other members of this chaperone family,
      however, suggest that the Hsc66/Hsc20 system will display different peptide
      binding specificity and that it is likely to be subject to different regulatory
      mechanisms. The high level of constitutive expression and the lack of a major
      response to temperature changes suggest that Hsc66 and Hsc20 play an important
      cellular role(s) under non-stress conditions.

PMID- 9144777
TI  - Consistency in structural energetics of protein folding and peptide recognition.
AB  - We report a new free energy decomposition that includes structure-derived atomic
      contact energies for the desolvation component, and show that it applies equally
      well to the analysis of single-domain protein folding and to the binding of
      flexible peptides to proteins. Specifically, we selected the 17 single-domain
      proteins for which the three-dimensional structures and thermodynamic unfolding
      free energies are available. By calculating all terms except the backbone
      conformational entropy change and comparing the result to the experimentally
      measured free energy, we estimated that the mean entropy gain by the backbone
      chain upon unfolding (delta Sbb) is 5.3 cal/K per mole of residue, and that the
      average backbone entropy for glycine is 6.7 cal/K. Both numbers are in close
      agreement with recent estimates made by entirely different methods, suggesting a
      promising degree of consistency between data obtained from disparate sources. In
      addition, a quantitative analysis of the folding free energy indicates that the
      unfavorable backbone entropy for each of the proteins is balanced predominantly
      by favorable backbone interactions. Finally, because the binding of flexible
      peptides to receptors is physically similar to folding, the free energy function
      should, in principle, be equally applicable to flexible docking. By combining
      atomic contact energies, electrostatics, and sequence-dependent backbone entropy,
      we calculated a priori the free energy changes associated with the binding of
      four different peptides to HLA-A2, 1 MHC molecule and found agreement with
      experiment to within 10% without parameter adjustment.

PMID- 9144778
TI  - Hexafluoroacetone hydrate as a structure modifier in proteins: characterization
      of a molten globule state of hen egg-white lysozyme.
AB  - A molten globule-like state of hen egg-white lysozyme has been characterized in
      25% aqueous hexafluoroacetone hydrate (HFA) by CD, fluorescence, NMR, and H/D
      exchange experiments. The far UV CD spectra of lysozyme in 25% HFA supports
      retention of native-like secondary structure while the loss of near UV CD bands
      are indicative of the overall collapse of the tertiary structure. The
      intermediate state in 25% HFA exhibits an enhanced affinity towards the
      hydrophobic dye, ANS, and a native-like tryptophan fluorescence quenching. 1-D
      NMR spectra indicates loss of native-like tertiary fold as evident from the
      absence of ring current-shifted 1H resonances. CD, fluorescence, and NMR suggest
      that the transition from the native state to a molten globule state in 25% HFA is
      a cooperative process. A second structural transition from this compact molten
      globule-like state to an "open" helical state is observed at higher
      concentrations of HFA (> or = 50%). This transition is characterized by a
      dramatic loss of ANS binding with a concomitant increase in far UV CD bands. The
      thermal unfolding of the molten globule state in 25% HFA is sharply cooperative,
      indicating a predominant role of side-chain-side-chain interactions in the
      stability of the partially folded state. H/D exchange experiments yield higher
      protection factors for many of the backbone amide protons from the four alpha
      helices along with the C-terminal 3(10) helix, whereas little or no protection is
      observed for most of the amide protons from the triple-stranded antiparallel beta
      sheet domain. This equilibrium molten globule-like state of lysozyme in 25% HFA
      is remarkably similar to the molten globule state observed for alpha-lactalbumin
      and also with the molten globule state transiently observed in the kinetic
      refolding experiments of hen lysozyme. These results suggest that HFA may prove
      generally useful as a structure modifier in proteins.

PMID- 9144779
TI  - Cysteine reactivity in Thermoanaerobacter brockii alcohol dehydrogenase.
AB  - The free cysteine residues in the extremely thermophilic Thermoanaerobacter
      brockii alcohol dehydrogenase (TBADH) were characterized using selective chemical
      modification with the stable nitroxyl biradical bis(1-oxy-2,2,5,5-tetramethyl-3
      imidazoline-4-yl)disulfide, via a thiol-disulfide exchange reaction and with
      2[14C]iodoacetic acid, via S-alkylation. The respective reactions were monitored
      by electron paramagenetic resonance (EPR) and by the incorporation of the
      radioactive label. In native TBADH, the rapid modification of one cysteine
      residue per subunit by the biradical and the concomitant loss of catalytic
      activity was reversed by DTT. NADP protected the enzyme from both modification
      and inactivation by the biradical. RPLC fingerprint analysis of reduced and S
      carboxymethylated lysyl peptides from the radioactive alkylated enzyme identified
      Cys 203 as the readily modified residue. A second cysteine residue was rapidly
      modified with both modification reagents when the catalytic zinc was removed from
      the enzyme by o-phenanthroline. This cysteine residue, which could serve as a
      putative ligand to the active-site zinc atom, was identified as Cys 37 in RPLC.
      The EPR data suggested a distance of < or 10 A between Cys 37 and Cys 203.
      Although Cys 283 and Cys 295 were buried within the protein core and were not
      accessible for chemical modification, the two residues were oxidized to cystine
      when TBADH was heated at 75 degrees C, forming a disulfide bridge that was not
      present in the native enzyme, without affecting either enzymatic activity or
      thermal stability. The status of these cysteine residues was verified by site
      directed mutagenesis.

PMID- 9144780
TI  - Energy profile of maltooligosaccharide permeation through maltoporin as derived
      from the structure and from a statistical analysis of saccharide-protein
      interactions.
AB  - The crystal structure of the maltodextrin-specific porin from Salmonella
      typhimurium ligated with a maltotrioside at the pore eyelet is known at 2.4 A
      resolution. The three glucose units assume a conformation close to the natural
      amylose helix. The pore eyelet fits exactly the cross-section of a
      maltooligosaccharide chain and thus functions as a constraining orifice. The
      oligomer permeates the membrane by screwing along the amylose helix through this
      orifice. Because each glucose glides along the given helix, its interactions can
      be sampled at any point along the pathway. The interactions are mostly hydrogen
      bonds, but also contacts to aromatic rings at one side of the pore. We have
      derived the energy profile of a gliding maltooligosaccharide by following
      formation and breakage of hydrogen bonds and by assessing the saccharide
      aromatics interactions from a statistical analysis of saccharide binding sites in
      proteins. The resulting profile indicates smooth permeation despite extensive
      hydrogen bonding at the orifice.

PMID- 9144781
TI  - Kaj Ulrik Linderstrom-Lang (1896-1959).
AB  - The Carlsberg Laboratory in Copenhagen has had a long tradition of outstanding
      science. At the time covered by this discussion, Kjeldahl, Sorensen, and
      Linderstrom-Lang had been consecutive directors of the Chemical Laboratory for 83
      years. Lang's inspired leadership began in the 1930s with a number of innovations
      (study of metabolism in single cells, titrations in non-aqueous solvents,
      relation of proteolysis to structure) but it was not until the early 1950s that
      Denmark had sufficiently recovered from the war for the laboratory to enter world
      science again. During World War II, Lang had been active in the Danish resistance
      movement. After the war, a number of major advances were being made that would
      revolutionize the field of protein chemistry (Pauling and Corey's H-bonded
      structures, Sanger's sequencing techniques, chromatography, Watson and Crick
      structures, modern instrumentation). The time for the new field of the physical
      biochemistry of proteins had arrived. Lang, with his broad experience,
      adventurous spirit, and genius for innovation, created an environment that was
      ideal for the convergence of these disconnected advances into a uniform science.
      The emphasis was to be on quantitative measurements on proteins in solution with
      interpretations based on molecular structures. During an all-too-brief period of
      time, Lang's laboratory attracted a large fraction of those who were destined to
      be the leaders of the next generation of protein chemists. At this time, the
      Carlsberg Laboratory was probably the most scientifically exciting environment
      for a protein chemist. The methods developed at that time-hydrogen exchange,
      limited proteolysis, optical rotatory dispersion, volume changes accompanying
      protein reactions, automatic titrations-are still all in common use and many of
      the visitors to the laboratory in that period and their students are still
      playing major roles in protein research. Lang's other qualities should not be
      ignored. He was not only a great scientist but also a musician, raconteur,
      artist, and an exceptionally warm and compassionate human being.

PMID- 9144783
TI  - Identification and structural influence of a differentially modified N-terminal
      methionine in human S100b.
AB  - The calcium-binding protein S100b is a homodimer comprised of two identical 91
      residue beta-subunits. Recombinant S100b is a heterogeneous protein, although the
      basis of this heterogeneity has not been established. We have used mass
      spectrometry and NMR spectroscopy to determine that heterogeneity in S100b arises
      from a mixture of formyl-S100b and desformyl-S100b when expressed in Escherichia
      coli. Reversed-phase HPLC purification of these two forms of S100b has allowed
      the differences in N-terminal composition to be used as a probe for tertiary
      contacts in the protein. The presence or absence of the N-terminal formyl group
      affected the chemical shifts of sequence neighboring residues and those in the
      linker of the protein (residues 40-43), indicating that these two regions are
      close in space.

PMID- 9144782
TI  - Hydrogen exchange: the modern legacy of Linderstrom-Lang.
AB  - This discussion, prepared for the Protein Society's symposium honoring the 100th
      anniversary of Kaj Linderstrom-Lang, shows how hydrogen exchange approaches
      initially conceived and implemented by Lang and his colleagues some 50 years ago
      are contributing to current progress in structural biology. Examples are chosen
      from the active protein folding field. Hydrogen exchange methods now make it
      possible to define the structure of protein folding intermediates in various
      contexts: as tenuous molten globule forms at equilibrium under destabilizing
      conditions, in kinetic intermediates that exist for less than one second, and as
      infinitesimally populated excited state forms under native conditions. More
      generally, similar methods now find broad application in studies of protein
      structure, energetics, and interactions. This article considers the rise of these
      capabilities from their inception at the Carlsberg Labs to their contemporary
      role as a significant tool of modern structural biology.

PMID- 9144784
TI  - Comparison of high-resolution structures of the diphtheria toxin repressor in
      complex with cobalt and zinc at the cation-anion binding site.
AB  - The diphtheria toxin repressor (DtxR) from Corynebacterium diphtheriae is a
      divalent-metal activated repressor of chromosomal genes responsible for
      siderophore-mediated iron-uptake and of a gene on several corynebacteriophages
      that encodes diphtheria toxin. Even though DtxR is the best characterized iron
      dependent repressor to date, numerous key properties of the protein still remain
      to be explained. One is the role of the cation-anion pair discovered in its first
      metal-binding site. A second is the reason why zinc exhibits its activating
      effect only at a concentration 100-fold higher than other divalent cations. In
      the presently reported 1.85 A resolution Co-DtxR structure at 100K, the sulfate
      anion in the cation-anion-binding site interacts with three side chains that are
      all conserved in the entire DtxR family, which points to a possible physiological
      role of the anion. A comparison of the 1.85 A Cobalt-DtxR structure at 100K and
      the 2.4 A Zinc-DtxR structure at room temperature revealed no significant
      differences. Hence, the difference in efficiency of Co2+ and Zn2+ to activate
      DtxR remains a mystery and might be hidden in the properties of the intriguing
      second metal-binding site. Our studies do, however, provide a high resolution
      view of the cationanion-binding site that has most likely evolved to interact not
      only with a cation but also with the anion in a very precise manner.

PMID- 9144785
TI  - My interests in protein and glycoprotein chemistry.

PMID- 9144786
TI  - Prediction of the structure of the replication initiator protein DnaA.
AB  - The secondary structure of DnaA protein and its interaction with DNA and
      ribonucleotides has been predicted using biochemical, biophysical techniques, and
      prediction methods based on multiple-sequence alignment and neural networks. The
      core of all proteins from the DnaA family consists of an "open twisted alpha/beta
      structure," containing five alpha-helices alternating with five beta-strands. In
      our proposed structural model the interior of the core is formed by a parallel
      beta-sheet, whereas the alpha-helices are arranged on the surface of the core.
      The ATP-binding motif is located within the core, in a loop region following the
      first beta-strand. The N-terminal domain (80 aa) is composed of two alpha
      helices, the first of which contains a potential leucine zipper motif for
      mediating protein-protein interaction, followed by a beta-strand and an
      additional alpha-helix. The N-terminal domain and the alpha/beta core region of
      DnaA are connected by a variable loop (45-70 aa); major parts of the loop region
      can be deleted without loss of protein activity. The C-terminal DNA-binding
      domain (94 aa) is mostly alpha-helical and contains a potential helix-loop-helix
      motif. DnaA protein does not dimerize in solution; instead, the two longest C
      terminal alpha-helices could interact with each other, forming an internal
      "coiled coil" and exposing highly basic residues of a small loop region on the
      surface, probably responsible for DNA backbone contacts.

PMID- 9144787
TI  - NADP-dependent enzymes. I: Conserved stereochemistry of cofactor binding.
AB  - The ubiquitous redox cofactors nicotinamide adenine dinucleotides [NAD and NADP]
      are very similar molecules, despite their participation in substantially
      different biochemical processes. NADP differs from NAD in only the presence of an
      additional phosphate group esterified to the 2'-hydroxyl group of the ribose at
      the adenine end and yet NADP is confined with few exceptions to the reactions of
      reductive biosynthesis, whereas NAD is used almost exclusively in oxidative
      degradations. The discrimination between NAD and NADP is therefore an impressive
      example of the power of molecular recognition by proteins. The many known
      tertiary structures of NADP complexes affords the possibility for an analysis of
      their discrimination. A systematic analysis of several crystal structures of
      NAD(P)-protein complexes show that: 1) the NADP coenzymes are more flexible in
      conformation than those of NAD; 2) although the protein-cofactor interactions are
      largely conserved in the NAD complexes, they are quite variable in those of NADP;
      and 3) in both cases the pocket around the nicotinamide moiety is substrate
      dependent. The conserved and variable interactions between protein and cofactors
      in the respective binding pockets are reported in detail. Discrimination between
      NAD and NADP is essentially a consequence of the overall pocket and not of a few
      residues. A clear fingerprint in NAD complexes is a carboxylate side chain that
      chelates the diol group at the ribose near the adenine, whereas in NADP complexes
      an arginine side chain faces the adenine plane and interacts with the
      phosphomonoester. The latter type of interaction might be a general feature of
      recognition of nucleotides by proteins. Other features such as strand-like
      hydrogen bonding between the NADP diphosphate moieties and the protein are also
      significant. The NADP binding pocket properties should prove useful in protein
      engineering and design.

PMID- 9144788
TI  - NADP-dependent enzymes. II: Evolution of the mono- and dinucleotide binding
      domains.
AB  - Nicotinamide adenine dinucleotides [NAD and NADP with both referred to as NAD(P)]
      are among the more diffuse redox cofactors. Despite their stereochemical
      similarity where the only difference is a phosphomonoester on the ribose near the
      adenine of NADP, they show different biochemical reactivities with NAD behaving
      as an oxidant and NADP as a reductant. NAD(P)-dependent enzymes generally share a
      common open alpha/beta fold with few exceptions only recently structurally
      characterized. This study of the molecular evolution of the NAD(P) binding
      domains, possible given the large number of known molecular structures, addresses
      two main questions: 1) can a common fold exist in different biological systems
      (divergent evolution) and 2) does a relationship exist among similar biological
      systems that display different folds (convergent evolution)? Both the structures
      of mono- and dinucleotide binding domains have been classified by cluster
      analysis based on the similarity evaluated by their main chain C alpha
      superposition. Moreover, the cofactor conformations and the stereochemical
      characteristics of their pockets have also been classified by analogous methods
      on the basis of the published tertiary structures. Two primary results appear: 1)
      the classification of the mononucleotide binding domains is different from that
      of the dinucleotide binding folds and 2) both divergent and convergent
      evolutionary pathways can be hypothesized, the latter less frequently observed
      and less pronounced but nevertheless evident. The generally accepted hypothesis
      that dinucleotide binding domains have evolved by gene duplication of primordial
      genes coding for the smaller mononucleotide binding domains is acceptable but the
      two halves of the resulting dinucleotide binding domains are evolutionarily
      uncorrelated. The NH2-terminal mononucleotide binding domain is less variable
      than the COOH-terminal half, probably because it involves the binding of the ADP
      moiety of NAD(P) invariant in all examined systems. There is evidence to
      postulate that evolutionary pathways for NAD(P)-dependent enzymes are both
      divergent and convergent. In fact, nearly all combinations of similarity
      dissimilarity in overall fold, cofactor conformation, and cofactor binding pocket
      structural characteristics for each enzyme pair examined are possible. The NAD(P)
      dependent enzymes apparently provide a canonical example of an evolutionary
      principle that "anything goes."

PMID- 9144789
TI  - The high-resolution crystal structure of a 24-kDa gyrase B fragment from E. coli
      complexed with one of the most potent coumarin inhibitors, clorobiocin.
AB  - Coumarin antibiotics, such as clorobiocin, novobiocin, and coumermycin A1,
      inhibit the supercoiling activity of gyrase by binding to the gyrase B (GyrB)
      subunit. Previous crystallographic studies of a 24-kDa N-terminal domain of GyrB
      from E. coli complexed with novobiocin and a cyclothialidine analogue have shown
      that both ligands act by binding at the ATP-binding site. Clorobiocin is a
      natural antibiotic isolated from several Streptomyces strains and differs from
      novobiocin in that the methyl group at the 8 position in the coumarin ring of
      novobiocin is replaced by a chlorine atom, and the carbamoyl at the 3' position
      of the noviose sugar is substituted by a 5-methyl-2-pyrrolylcarbonyl group. To
      understand the difference in affinity, in order that this information might be
      exploited in rational drug design, the crystal structure of the 24-kDa GyrB
      fragment in complex with clorobiocin was determined to high resolution. This
      structure was determined independently in two laboratories, which allowed the
      validation of equivalent interpretations. The clorobiocin complex structure is
      compared with the crystal structures of gyrase complexes with novobiocin and 5'
      adenylyl-beta, gamma-imidodiphosphate, and with information on the bound
      conformation of novobiocin in the p24-novobiocin complex obtained by
      heteronuclear isotope-filtered NMR experiments in solution. Moreover, to
      understand the differences in energetics of binding of clorobiocin and novobiocin
      to the protein, the results from isothermal titration calorimetry are also
      presented.

PMID- 9144790
TI  - Gas phase hydrogen/deuterium exchange reactions of peptide ions in a quadrupole
      ion trap mass spectrometer.
AB  - Hydrogen/deuterium exchange reactions of protonated and sodium cationized peptide
      molecules have been studied in the gas phase with a MALDI/quadrupole ion trap
      mass spectrometer. Unit-mass selected precursor ions were allowed to react with
      deuterated ammonia introduced into the trap cell by a pulsed valve. The reactant
      gas pressure, reaction time, and degree of the internal excitation of reactant
      ions were varied to explore the kinetics of the gas phase isotope exchange.
      Protonated peptide molecules exhibited a high degree of reactivity, some showing
      complete exchange of all labile hydrogen atoms. On the contrary, peptide
      molecules cationized with sodium exhibited only very limited reactivity,
      indicating a vast difference between the gas phase structures of the two ions.

PMID- 9144791
TI  - Curious structure in "canonical" alanine-based peptides.
AB  - We have performed all atom simulations of blocked peptides of the form (AAXAA)3,
      where X = Gln, Asn, Glu, Asp, Arg, and Lys with explicit water molecules to
      examine the interactions between side chains spaced i,i-5 in the sequence.
      Although side chains in this i,i-5 arrangement are commonly believed to be
      noninteracting, we have observed the formation of unusual i,i-5 main chain
      hydrogen bonding in such sequences with positively charged residues (Lys) as well
      as polar uncharged groups (Gln). Our results are consistent with the unusual
      percentage of hydrogen bonding curves produced by amide exchange measurements on
      the well-studied sequence acetyl-(AAQAA)3-amide in water (Shalongo, W., Dugad,
      L., Stellwagen, E. J. Am. Chem. Soc. 116:8288-8293, 1994). Analysis of our
      simulations indicated that the glutamine side chain showed the greatest
      propensity to support pi helix formation and that the i,i-5 intramolecular
      hydrogen bonds were stabilized by water-bridging side chain interactions. This
      intermittent formation of the unusual pi helix structure was observed for up to
      23% of the total simulation time in some residues in (AAQAA)3. Control studies on
      peptides with glutamine side chains spaced i,i-3, i,i-4 and i,i-6 did not reveal
      similar unique structures, providing stronger evidence for the unique role side
      chain interactions with i,i-5 spacing.

PMID- 9144792
TI  - An evolutionary treasure: unification of a broad set of amidohydrolases related
      to urease.
AB  - The recent determination of the three-dimensional structure of urease revealed
      striking similarities of enzyme architecture to adenosine deaminase and
      phosphotriesterase, evidence of a distant evolutionary relationship that had gone
      undetected by one-dimensional sequence comparisons. Here, based on an analysis of
      conservation patterns in three dimensions, we report the discovery of the same
      active-site architecture in an even larger set of enzymes involved primarily in
      nucleotide metabolism. As a consequence, we predict the three-dimensional fold
      and details of the active site architecture for dihydroorotases, allantoinases,
      hydantoinases, AMP-, adenine and cytosine deaminases, imidazolonepropionase,
      aryldialkylphosphatase, chlorohydrolases, formylmethanofuran dehydrogenases, and
      proteins involved in animal neuronal development. Two member families are common
      to archaea, eubacteria, and eukaryota. Thirteen other functions supported by the
      same structural motif and conserved chemical mechanism apparently represent later
      adaptations for different substrate specificities in different cellular contexts.

PMID- 9144793
TI  - Helical preferences of alanine, glycine, and aminoisobutyric homopeptides.
AB  - The stability between helical conformations of homopeptides of alanine, glycine,
      and aminoisobutyric acid has been studied by means of quantum-mechanical methods.
      The influence of peptide length on the relative stability between helical
      conformations has also been analyzed by means of systematic studies for peptides
      of size up to 11 residues. Finally, the influence of the solvent has been
      examined by using self-consistent reaction field methods. The results provide a
      detailed picture of the modulation exerted by these factors on the helical
      preferences of these peptides.

PMID- 9144794
TI  - A probable conformational difference between recombinant and urinary
      erythropoietins.
AB  - Urinary and recombinant human erythropoietin differ with respect to ease of
      iodination, inactivation by iodination, second derivative and circular dichroic
      spectra, rate of inactivation by trypsin and glycosylation pattern. All of these
      differences are compatible with a significant difference in conformation of these
      two forms of erythropoietin.

PMID- 9144795
TI  - Disposition of amphiphilic helices in heteropolar environments.
AB  - It is known that alpha helices in globular proteins usually consist of two types
      of residues, hydrophobic and hydrophilic, with the number of each type being
      roughly equal. Except for many transmembrane helices, alpha-helices are generally
      amphiphilic to some degree. This is not entirely surprising because alpha-helices
      typically reside in heteropolar environments that arise from the polar aqueous
      solution that surrounds a protein and the apolar "hydrophobic core" located at
      its center. The packing of alpha-helices in such heteropolar environments is
      driven by the minimization of free energy brought about by placing hydrophobic
      sidechains into apolar environments and hydrophilic sidechains into polar
      environments. The interface between the two environments can be characterized by
      an interfacial plane, called the demarcation plane, that optimally separates the
      two classes of residues. The inclination angle omega between the axis of the
      helix and the demarcation plane provides a measure of the degree of
      amphiphilicity of an alpha-helix. For highly amphiphilic helices, omega
      approximately 0. The inclination angle provides a new measure of amphiphilicity
      that complements the hydrophobic moments of Eisenberg et al. Based on the simple
      physical model described above, an algorithm is developed for predicting the
      helix inclination angle. The calculated results show that the inclination angle
      for most alpha-helices extracted from globular proteins is less than 25 degrees
      in magnitude. This suggests that helices found in globular proteins tend to be
      reasonably amphiphilic with half their face dominated by hydrophobic residues and
      the other half by hydrophilic residues. A new two-dimensional representation that
      characterizes the disposition of hydrophobic and hydrophilic residues in alpha
      helices, called a "wenxiang diagram," is presented. The wenxiang diagram can also
      be used as an important element to represent a protein molecule.

PMID- 9144796
TI  - Mechanical property of a TIM-barrel protein.
AB  - The mechanical response of a TIM-barrel protein to an applied pressure has been
      studied. We generated structures under an applied pressure by assuming the volume
      change to be a linear function of normal mode variables. By Delaunay
      tessellation, the space occupied by protein atoms is divided uniquely into
      tetrahedra, whose four vertices correspond to atomic positions. Based on the
      atoms that define them, the resulting Delaunay tetrahedra are classified as
      belonging to various secondary structures in the protein. The compressibility of
      various regions identified with respect to secondary structural elements in this
      protein is obtained from volume changes of respective regions in two structures
      with and without an applied pressure. We found that the beta barrel region
      located at the core of the protein is quite soft. The interior of the beta
      barrel, occupied by side chains of beta strands, is the softest. The helix,
      strand, and loop segments themselves are extremely rigid, while the regions
      existing between these secondary structural elements are soft. These results
      suggest that the regions between secondary structural elements play an important
      role in protein dynamics. Another aspect of tetrahedra, referred to as bond
      distance, is introduced to account for rigidities of the tetrahedra. Bond
      distance is a measure of separation of the atoms of a tetrahedron in terms of
      number of bonds along the polypeptide chain or side chains. Tetrahedra with
      longer bond distances are found to be softer on average. From this behavior, we
      derive a simple empirical equation, which well describes the compressibilities of
      various regions.

PMID- 9144797
TI  - Structural basis for thermostability and identification of potential active site
      residues for adenylate kinases from the archaeal genus Methanococcus.
AB  - Sequence comparisons of highly related archaeal adenylate kinases (AKs) from the
      mesophilic Methanococcus voltae, the moderate thermophile Methanococcus
      thermolithotrophicus, and two extreme thermophiles Methanococcus igneus and
      Methanococcus jannaschii, allow identification of interactions responsible for
      the large variation in temperatures for optimal catalytic activity and
      thermostabilities observed for these proteins. The tertiary structures of the
      methanococcal AKs have been predicted by using homology modeling to further
      investigate the potential role of specific interactions on thermal stability and
      activity. The alignments for the methanococcal AKs have been generated by using
      an energy-based sequence-structure threading procedure against high-resolution
      crystal structures of eukaryotic, eubacterial, and mitochondrial adenylate and
      uridylate (UK) kinases. From these alignments, full atomic model structures have
      been produced using the program MODELLER. The final structures allow
      identification of potential active site interactions and place a polyproline
      region near the active site, both of which are unique to the archaeal AKs. Based
      on these model structures, the additional polar residues present in the
      thermophiles could contribute four additional salt bridges and a higher negative
      surface charge. Since only one of these possible salt bridges is interior, they
      do not appear significantly to the thermal stability. Instead, our model
      structures indicate that a larger and more hydrophobic core, due to a specific
      increase in aliphatic amino acid content and aliphatic side chain volume, in the
      thermophilic AKs is responsible for increased thermal stability.

PMID- 9144798
TI  - Crystallization and preliminary diffraction analysis of Ca(2+)-calmodulin-drug
      and apocalmodulin-drug complexes.
AB  - Ca(2+)-calmodulin is crystallized with two new and potent drugs: a bisindol
      derivative (KAR-2, 3"-(beta-chloroethyl)-2",4"-dioxo-3,5"- spiro-oxazolidino-4
      deacetoxy-vinblastine) with antitumor activity and an arylalkylamine fendiline
      analogue (N-(3,3-diphenylpropyl)-N'-[1-(3,4- di-n-butoxy-phenyl)-ethyl]-1,3
      diaminopropane) with anticalmodulin activity. The crystals diffract beyond 2.8 A
      and differ in unit cell parameters from each other as well as from crystals of
      Ca(2+)-calmodulin or Ca(2+)-calmodulin-ligand complexes, as reported thus far.
      Attempts to crystallize Ca(2+)-free calmodulin without drugs failed, in
      consonance with earlier results; however, single Ca(2+)-free calmodulin crystals
      diffracting-beyond 2.5 A resolution were grown in the presence of KAR-2. Results
      indicate that binding of the two drugs to apocalmodulin or Ca(2+)-calmodulin may
      induce unique novel protein conformers, targets of further detailed X-ray
      studies.

PMID- 9144799
TI  - Crystallization and preliminary X-ray analysis of Escherichia coli peptidyl-tRNA
      hydrolase.
AB  - Peptidyl-tRNA hydrolase from Escherichia coli, a monomer of 21 kDa, was
      overexpressed from its cloned gene pth and crystallized by using polyethylene
      glycol as precipitant. The crystals are orthorhombic and have unit cell
      parameters a = 47.24 A, b = 63.59 A, and c = 62.57 A. They belong to space group
      P2(1)2(1)2(1) and diffract to better than 1.2 A resolution. The structure is
      being solved by multiple isomorphous replacement.

PMID- 9144800
TI  - Crystallization and preliminary X-ray studies of I-CreI: a group I intron-encoded
      endonuclease from C. reinhardtii.
AB  - Group I intron endonuclease I-CreI is encoded by an open reading frame contained
      within a self-splicing intron in the Chlamydomonas reinhardtii chloroplast 23S
      rRNA gene. I-CreI initiates the lateral transfer or homing of this intron by
      specifically recognizing and cleaving a pseudopalindromic 19-24 bp homing site in
      chloroplast 23S rRNA genes that lack the intron. The gene encoding this enzyme
      has been subcloned, and the protein product has been purified and crystallized.
      The crystals belong to space group P321, with unit cell dimensions a = b = 78.2
      A, c = 67.4 A. The crystal unit cell is consistent with an asymmetric unit
      consisting of the enzyme monomer. The specific volume of this unit cell is 3.3
      A3/Da. The crystals diffract to at least 3.0 A resolution after flash-cooling,
      when using a rotating anode x-ray source and an RAXIS image plate detector.

PMID- 9144801
TI  - Psychiatrists as gatekeepers: a matter of perspective.

PMID- 9144802
TI  - Taking issue with Taking Issue: "psychiatric survivors" reconsidered.

PMID- 9144803
TI  - Taking issue with Taking Issue: "psychiatric survivors" reconsidered.

PMID- 9144804
TI  - Taking issue with Taking Issue: "psychiatric survivors" reconsidered.

PMID- 9144805
TI  - Taking issue with Taking Issue: "psychiatric survivors" reconsidered.

PMID- 9144806
TI  - Taking issue with Taking Issue: "psychiatric survivors" reconsidered.

PMID- 9144807
TI  - Taking issue with Taking Issue: "psychiatric survivors" reconsidered.

PMID- 9144808
TI  - Taking issue with Taking Issue: "psychiatric survivors" reconsidered.

PMID- 9144809
TI  - Taking issue with Taking Issue: "psychiatric survivors" reconsidered.

PMID- 9144810
TI  - Taking issue with Taking Issue: "psychiatric survivors" reconsidered.

PMID- 9144811
TI  - Taking issue with Taking Issue: "psychiatric survivors" reconsidered.

PMID- 9144812
TI  - Taking issue with Taking Issue: "psychiatric survivors" reconsidered.

PMID- 9144814
TI  - Interactive voice response systems in clinical research and treatment.

PMID- 9144813
TI  - Taking issue with Taking Issue: "psychiatric survivors" reconsidered.

PMID- 9144815
TI  - Using signs of decompensation as triggers for early intervention to reduce
      hospitalization.

PMID- 9144816
TI  - Occupational therapy evaluation and intervention in an employment program for
      homeless youths.

PMID- 9144818
TI  - Assessing and developing readiness for psychiatric rehabilitation.

PMID- 9144817
TI  - Movement disorders and substance abuse.

PMID- 9144819
TI  - Essential skills for managed behavioral health care.
AB  - Pressure from payers for cost containment and accountability is forcing
      clinicians to refine existing skills and develop new areas of competence. To
      adequately address patients' needs in the new health care environment, clinicians
      must master at least six skill sets and the individual skills within each set.
      This paper describes six core skill sets-clinical care skills, clinical
      management skills, clinical knowledge, skills with special populations,
      administrative competence, and ethical care management-and specific skills within
      each set. These descriptions are intended to serve as a how-to manual for modern
      behavioral practice.

PMID- 9144820
TI  - Homelessness, severe mental illness, and the institutional circuit.
AB  - OBJECTIVE: Research on homelessness among persons with severe mental illness
      tends to focus on aspects of demand, such as risk factors or structural and
      economic forces. The authors address the complementary role of supply factors,
      arguing that "solutions" to residential instability-typically, a series of
      institutional placements alternating with shelter stays-effectively perpetuate
      homelessness among some persons with severe mental illness. METHODS: Thirty-six
      consecutive applicants for shelter in Westchester County, New York, in the first
      half of 1995 who were judged to be severely mentally ill by intake workers were
      interviewed using a modified life chart format. Detailed narrative histories were
      constructed and reviewed with the subjects. RESULTS: Twenty of the 36 subjects
      had spent a mean of 59 percent of the last five years in institutions and
      shelters. Analysis of the residential histories of the 36 subjects revealed that
      shelters functioned in four distinctive ways in their lives: as part of a more
      extended institutional circuit, as a temporary source of transitional housing, as
      a surrogate for exhausted support from kin, and as a haphazard resource in
      essentially nomadic lives. The first pattern dominated in this group.
      CONCLUSIONS: Shelters and other custodial institutions have acquired hybrid
      functions that effectively substitute for more stable and appropriate housing for
      some persons with severe mental illness.

PMID- 9144821
TI  - Estimating psychiatric manpower requirements based on patients' needs.
AB  - OBJECTIVE: To provide a better understanding of the complexities of estimating
      psychiatric manpower requirements, the authors describe several approaches to
      estimation and present a method based on patients' needs. METHODS: A five-step
      method for psychiatric manpower estimation is used, with estimates of data
      pertinent to each step, to calculate the total psychiatric manpower requirements
      for the United States. The method is also used to estimate the hours of
      psychiatric service per patient per year that might be available under current
      psychiatric practice and under a managed care scenario. RESULTS: Depending on
      assumptions about data at each step in the method, the total psychiatric manpower
      requirements for the U.S. population range from 2,989 to 358,696 full-time
      equivalent psychiatrists. The number of available hours of psychiatric service
      per patient per year is 14.1 hours under current psychiatric practice and 2.8
      hours under the managed care scenario. CONCLUSIONS: The key to psychiatric
      manpower estimation lies in clarifying the assumptions that underlie the specific
      method used. Even small differences in assumptions mean large differences in
      estimates. Any credible manpower estimation process must include discussions and
      negotiations between psychiatrists, other clinicians, administrators, and
      patients and families to clarify the treatment needs of patients and the roles,
      responsibilities, and job description of psychiatrists.

PMID- 9144822
TI  - Determinants of mental health providers' expectations of patients' improvement.
AB  - OBJECTIVE: Characteristics of individual mental health providers and of treatment
      settings were examined to determine their effects on providers' expectations
      about the improvement of patients with serious mental illness. METHODS: The
      sample consisted of 1,567 treatment providers working in 107 inpatient and
      outpatient units or programs in 29 Veterans Affairs mental health facilities.
      They completed a questionnaire about their prognostic expectations and a broad
      range of attitudes toward job satisfaction, professional relations, and team
      functioning. Unit or program directors of all 107 units completed another
      questionnaire about the average functional ability of patients, unit workload,
      and unit size. Hierarchical linear modeling was used to assess the effects of
      both individual and unit-level attributes on providers' expectations of
      improvement in clinical symptomatology and social-functional skills of patients
      in their care. RESULTS: The providers had generally low expectations about the
      improvement of patients with serious mental illness. Expectations were higher
      among staff in units or programs that were smaller and that had an outpatient
      focus, a greater proportion of staff involved in the treatment team, and higher
      functioning patients. Individual characteristics significantly associated with
      prognostic expectations were occupation, age, and membership on the treatment
      team. CONCLUSIONS: Prognostic expectations among providers of care to persons
      with serious mental illness vary with identifiable individual and unit or program
      characteristics. The latter may be amenable to manipulation and intervention to
      improve mental health providers' prognostic expectations.

PMID- 9144823
TI  - A prospective study of violence by psychiatric patients after hospital discharge.
AB  - OBJECTIVE: The study assessed the frequency of violence by patients two weeks
      after discharge from a psychiatric hospital and identified characteristics of
      patients with an increased risk of violence after discharge. METHODS: A
      structured form was used to interview patients aged 18 to 59 years in a private
      university psychiatric hospital. Patients provided self-reports of past violence,
      and violence while in the hospital was assessed by routine nurse ratings.
      Patients were telephoned two weeks after discharge to assess violence since
      discharge. RESULTS: Sixteen of 430 patients who were interviewed by telephone two
      weeks after discharge reported violence against persons since their discharge.
      Patients who were violent in the month before admission were nine times more
      likely to be violent in the two weeks after discharge, compared with patients who
      were not violent just before admission. Patients with a personality disorder were
      four times more likely than patients without a personality disorder to be violent
      after discharge. The targets of violence were often family members or other
      intimates and often the same persons attacked before hospitalization.
      CONCLUSIONS: Patients who were violent just before admission were more likely to
      be violent after discharge and to attack the same persons they had attacked in
      the past. Clinicians should routinely evaluate past violence and work with the
      patient and potential targets of violence to prevent future violence.

PMID- 9144825
TI  - Psychiatric findings among child psychiatric inpatients grouped by public and
      private payment.
AB  - OBJECTIVE: The study compared school-age psychiatric inpatients whose care was
      publicly funded with those whose care was privately funded to determine whether
      the public patients presented with more psychiatric risk factors and more
      psychiatric problems. METHODS: Retrospective chart review was used to collect
      data on the demographic and personal characteristics, behavior in the hospital,
      and response to milieu treatment of 40 public patients and 40 private patients.
      Half of each group were admitted during 1985-1986, and half during 1991-1993.
      Characteristics of the two groups were compared, and trends over time were
      examined. RESULTS: The public group presented for hospitalization with
      significantly more risk factors and psychiatric problems. Public status predicted
      the use of certain interventions, such as time-outs and physical holding. Public
      patients responded less positively to the treatment program. They had three times
      the number of bed-days as the private group during 1991-1993. CONCLUSIONS: Public
      patients require more intensive and extensive inpatient treatment and will be
      more profoundly affected by the restrictions on psychiatric inpatient care in the
      current climate of fiscal restraint.

PMID- 9144824
TI  - Effects of diagnosis, demographic characteristics, and case management on
      rehospitalization.
AB  - OBJECTIVES: A randomized controlled study was conducted to assess the effects of
      case management and patients' characteristics on the use of inpatient psychiatric
      services. METHODS: Inpatients discharged from Harlem Hospital Center in 1984-1985
      were randomly assigned to an outreach case management team or standard aftercare.
      Analysis of variance was used to assess the main effects and two- and three-way
      interaction effects of treatment status, gender, age, substance abuse, and
      diagnosis on the number of days of psychiatric rehospitalization in state and
      city community hospitals. RESULTS: In the follow-up period, 75 of the 146
      patients in the case management group (51.4 percent) and 51 of the 143 patients
      in the control group (35.7 percent) were rehospitalized for psychiatric care. On
      average, patients spent 31.1 days in city hospitals and 26.6 days in state
      hospitals. Members of the case management team spent a mean total of 18.1 hours a
      month in direct and indirect care for each patient. They spent most time with
      substance-abusing older women. Significant three-way interaction effects were
      found between treatment status and diagnosis and gender, diagnosis and age, and
      diagnosis and substance abuse on the number of days patients spent rehospitalized
      for psychiatric care in city and state hospitals. CONCLUSIONS: It is unlikely
      that case management intervention will reduce rehospitalization rates unless
      appropriate and effective outpatient and community services are available.
      Effective surveillance of patient populations by case managers frequently results
      in rehospitalization as the only treatment alternative if other options for
      meeting the needs and resolving the crises of patients are not available.

PMID- 9144826
TI  - Prevention of aggressive incidents on a closed psychiatric ward.
AB  - OBJECTIVE: This study examined whether staff members' use of interventions for
      preventing patients' aggression reduced the number of incidents of aggression on
      a closed acute admissions ward of a psychiatric hospital in the Netherlands.
      METHODS: The number and severity of incidents of aggression on three closed wards
      were measured using the Dutch version of the Staff Observation Aggression Scale
      (SOAS). Measurements were made for three months before and after staff
      implemented interventions for preventing aggression on one of the wards.
      Interventions included a protocol for talking to patients who exhibited
      aggressive behavior, discussing treatment goals with the patient shortly after
      admission, explaining why the ward's door was locked and the exit rules,
      providing a schedule of staff meetings to explain staff members' absence from the
      ward, and clarifying the procedure for making an appointment with the
      psychiatrists. RESULTS: The frequency of aggressive incidents was reduced on all
      three wards, with no significant difference between the ward where the
      interventions were implemented and the two control wards. A marginally
      significant difference in the severity of aggressive incidents was found between
      experimental and control wards after the introduction of the preventive measures,
      with incidents in the experimental ward tending to be less severe. CONCLUSIONS:
      This study failed to find a robust effect of specific intervention measures on
      aggressive incidents. However, it did find evidence suggesting that standardized
      reporting by staff of aggressive incidents on closed psychiatric wards may in
      itself result in straightforward reduction of violent incidents.

PMID- 9144827
TI  - Outcomes of inpatients treated on a VA psychiatric unit and a substance abuse
      treatment unit.
AB  - OBJECTIVE: The utility of the Treatment Outcome Profile (TOP) for measuring the
      effectiveness of acute inpatient psychiatric and substance abuse treatment was
      tested, including its internal reliability, validity, and sensitivity to
      treatment gains. The relationship between patients' satisfaction with services
      and treatment gains in quality of life, symptoms, and level of functioning was
      explored. METHODS: A pre-post research design was used with consecutive
      admissions to an inpatient psychiatric unit (N = 66) and a substance abuse
      treatment unit (N = 88) at a VA medical center. At admission and at discharge,
      the TOP, a self-report instrument assessing quality of life, symptoms, level of
      functioning, and patient satisfaction with services (at discharge only) was
      completed. Multivariate analysis of variance and univariate analysis of variance
      were used to test differences in scores between admission and discharge. RESULTS:
      Patients demonstrated significant treatment gains. Overall, compared with
      patients on the substance abuse unit, those receiving psychiatric treatment were
      more impaired at admission and had lower levels of self-reported therapeutic gain
      at discharge. Improvement for both groups occurred in quality of life, symptoms,
      and level of functioning. Both groups reported high levels of patient
      satisfaction, comparable with levels in other service industries. A high positive
      correlation (alpha = .61) was found between patient satisfaction and overall self
      reported treatment gain. CONCLUSIONS: The results indicate that it is important
      to compare treatment effectiveness as well as costs when seeking less costly
      alternatives to inpatient care. The TOP is a valid and sensitive outcome
      measurement tool. Patient satisfaction is an important outcome variable and
      positively related to treatment gains in quality of life, symptoms, and level of
      functioning.

PMID- 9144828
TI  - Measurement of depression and anxiety for hospitalized depressed patients.
AB  - Standard scales for measuring anxiety and depression did not distinguish between
      these two psychological constructs in a sample of 295 inpatients with major
      depressive disorder. Items from these scales were used to form new measures,
      based on the results of a factor analysis. The new depression and anxiety
      subscales were internally consistent and only moderately correlated with one
      another, compared with the standard measures, which were highly correlated. When
      the factorial procedure was repeated with a subsample of patients with only mild
      to moderate symptoms, there was no discrimination between depression and anxiety.
      This finding suggests that when measured in a sample with a restricted range of
      symptom severity, anxiety and depression have poor discriminant validity.

PMID- 9144829
TI  - A survey of professional activities of psychiatrists in South Africa.
AB  - To obtain information about practicing psychiatrists in South Africa, a
      questionnaire was mailed in 1993 to all 378 registered psychiatrists, of whom 210
      (55.6 percent) responded. After selected data for nonrespondents were obtained,
      information was available for 357, or 94.4 percent of registered psychiatrists.
      Of the 261 psychiatrists practicing in South Africa, 147 (56.3 percent) were in
      full-time private practice. There were 6.4 psychiatrists per million population,
      with large discrepancies between provinces. Only 7 percent of psychiatrists spent
      any time working in rural areas, and only 10.8 percent could communicate in one
      or more African languages. These findings emphasize the magnitude of the
      challenge of developing a primary mental health care system in postapartheid
      South Africa.

PMID- 9144830
TI  - Judges' assumptions about the appropriateness of civil and forensic commitment.
AB  - The study examined judges' reasons for ordering pretrial forensic evaluation
      instead of civil commitment for persons with mental illness who are arrested.
      Fifty-five of 58 judges acknowledged having concerns about the adequacy of
      treatment or confinement in the civil mental health system, and 31 reported
      ordering pretrial forensic evaluations as a means of ensuring adequate treatment
      for patients who appear in their courts. Other frequently endorsed reasons for
      ordering these evaluations included lack of confidence in the ability to civilly
      commit mentally ill offenders and concerns about their being discharged
      prematurely. This study confirms suspicions that judges order pretrial
      evaluations to fill perceived gaps in the civil system.

PMID- 9144831
TI  - Mechanism of nitric oxide production induced by H2O2 in cultured endothelial
      cells.
AB  - This study examined the mechanism of stimulation of nitric oxide (NO) synthesis
      induced by hydrogen peroxide (H2O2). To determine the role of Ca2+ on H2O2
      induced NO synthesis in bovine aortic endothelial cells, the increases in
      intracellular Ca2+ and NO production induced by H2O2 were compared with the
      effects of the Ca2+ ionophore ionomycin in the same batches of endothelial cells.
      NO production was assessed by formation of [3H]citrulline from [3H]arginine, and
      changes in intracellular Ca2+ were measured using fluorescent indicator fluo-3
      with a confocal laser scanning system. Both H2O2 (1-10 mM) and ionomycin (10(-7)
      10(-5) M) increased intracellular Ca2+ and stimulated the synthesis of L
      citrulline from L-arginine. Although H2O2 induced only a small increase in
      intracellular Ca2+, it markedly increased L-citrulline formation compared with
      ionomycin. Thus, stimulation of NO synthesis induced by H2O2 may involve the
      mechanisms other than the increases in intracellular Ca2+ in endothelial cells.
      In the particulate fraction from cultured endothelial cells, addition of
      exogenous H2O2 (1 mM) or catalase (100 U/ml) did not affect L-citrulline
      formation. However, co-administration of H2O2 and catalase stimulated L
      citrulline formation. These findings suggested that not only the increases in
      intracellular Ca2+ but also the products by the reaction with H2O2 and catalase
      are likely to be involved in the stimulation of NO synthesis induced by H2O2.

PMID- 9144832
TI  - The effect of 3-aminobenzamide, an inhibitor of poly-ADP-ribose polymerase, on
      ischemia/reperfusion damage in rat retina.
AB  - Excitotoxic amino acids, such as glutamate, may play an important role in retinal
      ischemia/reperfusion damage. In central neurons, excitotoxicity may be mediated
      by nitric oxide synthase (NOS) causing DNA damage via nitric oxide (NO). The
      nicked DNA activates poly-adenosine diphosphate (ADP)-ribose polymerase (PARP)
      and may deplete intracellular ATP resulting in cell death. PARP may also be
      involved in apoptosis. We used 3-aminobenzamide (3-ABA), a PARP inhibitor, to
      examine the possible involvement of PARP in a rat model of retinal ischemia.
      Retinal ischemia was induced by elevating the intraocular pressure (IOP) through
      the insertion of a needle into the anterior chamber of a rat eye. IOP was raised
      to 110 mm Hg for 60 minutes. Animals were given intracameral infusion of 0, 1, 3,
      10, 30, 100 mM 3-ABA in 0.1 M PBS, pH 7.4 during ischemia. Morphologic and
      morphometric evaluation at 7 days after reperfusion showed that 3-ABA at 3 mM and
      above significantly ameliorated the ischemic/reperfusion damage to the retina. In
      addition, at 10 mM 3-ABA inhibited the characteristic ladder pattern in DNA gel
      analysis seen in apoptosis of retinal neurons after ischemia/reperfusion. Hence,
      PARP may be involved in retinal cell loss after ischemia/reperfusion insult
      probably through the apoptotic pathway.

PMID- 9144833
TI  - DNA bases attack by reactive metabolites produced during carbon tetrachloride
      biotransformation and promotion of liver microsomal lipid peroxidation.
AB  - Free radicals produced during carbon tetrachloride biotransformation and the
      promoted lipid peroxidation process of liver microsomal lipids are able to attack
      the DNA bases guanine, cytosine and thymine to give at least three altered bases.
      They were identified as 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua); 5
      hydroxycytosine (5OHCyt) and 5-hydroxymethyluracil (5OHMeU). No adenine adducts
      were detected. If these altered bases were formed during carbon tetrachloride
      poisoning and were not adequately repaired before cell replication, serious
      permanent consequences for liver cell DNA could be expected and this might be
      somehow involved in the liver carcinogenic effects of the haloalkane.

PMID- 9144834
TI  - Effect of swimming training on antioxidant enzymes in kidney of young and old
      mice.
AB  - The current study was undertaken to investigate the effect of swimming training
      on the antioxidant enzyme system in kidney of young and old mice. Both young and
      old mice, aged 2 and 26 months old, respectively, were divided into the sedentary
      and swimming-trained groups. The trained mice underwent a 6-week swimming program
      (1 h/day, 5 days/week) in water at 35-36 degrees C. Cu,Zn-superoxide dismutase
      (Cu,Zn-SOD) activity was significantly decreased with aging but was not
      influenced by swimming training, such changes being similar to those noted for
      catalase activity rather than for glutathione peroxidase activity. After swimming
      training Mn-SOD activity increased significantly only in old mice but was
      unaffected by aging. Although neither aging nor swimming training had overt
      effect on the expression of Cu,Zn-SOD mRNA, the immunoreactive Cu,Zn-SOD content
      in young mice decreased significantly after the training. Meanwhile, Mn-SOD mRNA
      expression in old mice was reduced by half after swimming training, accompanied
      by a significant decrease in its immunoreactive content; unexpectedly, however,
      Mn-SOD content in young mice did not parallel its mRNA expression. These findings
      suggest that the antioxidant enzyme system in mouse kidney trends to be down
      regulated with aging, and that swimming training fails to attenuate such reduced
      levels of the antioxidant enzymes.

PMID- 9144835
TI  - Fractal analysis of lung alveoli during the acute phase vs. repair phase of an
      adenoviral infection in canines.
AB  - Acute viral respiratory infections are commonly associated with alterations in
      lung growth. Recently, fractal techniques have been demonstrated to show changes
      in alveolar perimeter after canine adenovirus type 2 (CAV2) infection in a beagle
      puppy model. In the present study, we investigated whether the fractal dimension
      (Df) of the alveolar perimeter was changed in the acute phase (2-3 weeks after
      inoculation, 131d CAV2 group) or during the recovery phase (approximately 22
      weeks after inoculation, 235d CAV2 group) after a single bout of CAV2. There were
      sham CAV2 groups, 130d and 238d controls, corresponding to the CAV2 groups. The
      Df of alveolar perimeter length was significantly increased in the 235d CAV2
      puppies compared to all of the other beagle puppy groups. On the other hand, the
      fractal dimensions for alveolar perimeter length for the other beagle puppy
      groups were very similar. In a related human study of patients (age range of 25 h
      to 19 y, N = 11), who died of non-respiratory causes, showed no consistent change
      in Df of alveolar perimeter length with normal lung growth and development. We
      conclude that fractal analysis of alveolar perimeter length can be used as an
      index of permanent lung injury after insult to the growing lungs.

PMID- 9144836
TI  - Effects of intravenous anesthetics on the contraction and response of rat trachea
      to phosphatidylinositol.
AB  - Some intravenous anaesthetics have significant effects on the tonicity of airway
      smooth muscle. There are evidences for a direct relationship between airway
      smooth muscle contraction and phosphatidylinositol (PI) response. The aims of
      this study were to clarify 1) the effects of anaesthetics on the cholinergically
      induced contraction, and 2) the relationship between the effects on the PI
      response and the contraction. Rat tracheal rings or slices were incubated in
      Krebs-Henseleit solution containing 5.5 microM carbachol (CCh) in the presence of
      varying doses of anaesthetics. Thiamylal, fentanyl, ketamine and midazolam all
      attenuated the CCh-induced contraction. On the other hand, thiamylal augmented
      inositol monophosphate (IP1) accumulation, whilst ketamine, midazolam and
      morphine did not have the effect, and fentanyl significantly attenuated IP1
      accumulation. These data suggest that airway smooth muscle can be relaxed by
      intravenous anaesthetics, and that the relaxing effects are not always dependent
      on the PI system.

PMID- 9144839
TI  - A quantitative structure activity study on a new class of highly potent
      antiinflammatory agents.
AB  - A structure-activity study was carried out for some new antiinflammatory
      compounds 2,3-dihydrobenzo-furan-2-ones, analogues of the natural product
      wortmannin (the mold metabolite), inhibitors of prostaglandin synthesis. The
      results show that lipophilicity and steric properties are very important in two
      testing models.

PMID- 9144838
TI  - 1-[3-(Aryloxy) propyl]-diamines: a new class of non-steroidal basic
      antiinflammatory agents. Structure-activity studies: Part II.
AB  - Six substituted aryloxy diamines, synthesized as potential new antiinflammatory
      agents, were tested in vivo and in vitro in order to evaluate their biological
      activities. These derivatives reduced significant carrageenin rat paw edema and
      showed antiproteolytic activity. The in vitro inhibition of soybean lipoxygenase
      ranged from 41-77%. The results are discussed from the view of structural
      modifications.

PMID- 9144837
TI  - Alteration in the biliary and urinary excretion of acetaminophen metabolites by
      nephrotoxicants in rats.
AB  - It has been shown that ureter ligation increases the biliary excretion of
      acetaminophen (AA) conjugates, mainly as the sulfate in rats. This study was
      conducted to examine the effect of nephrotoxicants-that induce renal damage
      without liver injury on the biliary and urinary excretion of AA metabolites.
      Renal damage was produced in male S.D. rats, 1 day after dosing with 200 mg/kg
      p.o. of hexachloro-1,3-butadiene (HCBD), or 3 day after the dosage of 7.5 mg/kg
      iv of cisplatin (CIS). Renal damage without liver injury was confirmed by
      measuring serum enzymes, creatinine and BUN levels. AA and its metabolites were
      measured for 3 hr by HPLC in rats injected iv with 150 mg/kg of AA. The excreted
      amounts of AA-glucuronide (AA-G), AA-sulfate (AA-S) and AA-glutathione into bile
      were reduced to 57, 18 and 73% of control rats, respectively, by HCBD. HCBD
      pretreatment also altered the urinary excretion of AA-G, AA-S and AA-mercapturate
      to 75, 14 and 118% of controls. CIS drastically reduced the urinary excretion of
      AA metabolites, whereas this compound significantly enhanced the biliary
      excretion of AA-S. However, CIS did not cause an increase in the percentage of
      the dose excreted as AA-G in bile. Both HCBD and CIS caused marked elevations in
      the blood concentrations of AA-G and AA-S. These findings suggest that: 1) not
      all renal malfunction results in increased biliary excretion of AA metabolites to
      compensate for the lack of renal elimination, and 2) the selective reduction in
      biliary and urinary excretion of AA-S by HCBD appears to occur by mechanism(s)
      other than through alteration of AA and its metabolites.

PMID- 9144840
TI  - The cytoprotective effect of iloprost against carbon tetrachloride induced
      necrosis in rat liver.
AB  - The aim of this study was to investigate the cytoprotective effect of Iloprost on
      the liver against carbon tetrachloride induced necrosis. The serum histamine-like
      activity was found to be increased when compared with that of controls after
      treatment with carbon tetrachloride for 18 weeks while prostaglandin E2- and
      leukotriene C4-like activities were unchanged. After pretreatment with Iloprost
      for 18 weeks the increased activity of histamine was found to be unchanged while
      prostaglandin E2-like activity was increased. It is concluded that Iloprost
      protects the liver against carbon tetrachloride-induced damage and reduces the
      level of histamine that has a role in the pathogenesis of portal hypertension.

PMID- 9144841
TI  - Effect of aging on the rate of muscle protein turnover in rat.
AB  - The urinary excretion of Nt-methylhistidine (e-methylhistidine, 3-MH, an index
      related to myofibrillar protein breakdown), as well as the rate of L-[14C]
      tyrosine incorporation into gastrocnemius muscle (ks, fractional rate of muscle
      protein synthesis, evaluated by the constant infusion method) have been measured
      to assess the effect of aging on the rate of skeletal muscle protein turnover. In
      addition, nucleic acids, muscle protein and serum corticosterone levels were
      determined. Weaning rats were fed a 10% lactalbumin diet and killed in groups of
      seven when they were 35, 60, 120 and 300 days old. Apart from the rate of growth,
      no major differences were found between 35- and 60-day old animals. However, as
      compared to the youngest rats, 120-day old rats showed a significant reduction in
      the relative weight of the four muscles excised. Plasma corticosterone levels,
      increased as the animals became older. Finally, in the 300-day old rats, the
      reduced rate of growth was accompanied by a significant reduction in the relative
      organ weight (with the exception of soleus), 3-MH and Ks. It is concluded that
      aging caused a reduction in the rates of both protein breakdown and synthesis.
      The reduced muscle breakdown may not be due to a relative reduced muscle mass in
      elder rats since urinary 3-MH remained low even when expressed per creatinine
      output.

PMID- 9144842
TI  - Comparative study of the effect of teicoplanin and vancomycin upon the phagocytic
      process of peritoneal macrophages.
AB  - The effect of Teicoplanin and Vancomycin upon the phagocytic process was compared
      by evaluating the different activities of the peritoneal macrophage phagocytic
      function from mice treated with these antibiotics. The results indicated that
      teicoplanin and vancomycin increased both the substrate adherence and chemotaxis
      of peritoneal macrophages and that neither antibiotic, at the concentrations of
      10, 25, 50, 75 and 100 mg/l, had any chemoattractant capacity for peritoneal
      macrophages. There was an increase in the attachment of Candida albicans only in
      the macrophages from mice treated with vancomycin. The phagocytosis of C.
      albicans, Staphylococcus aureus, Escherichia coli and inert particles as well, as
      the nitroblue tetrazolium reduction capacity (microbicide capacity) increased in
      the presence of both antibiotics. The C. albicans digestion capacity increased
      only in the peritoneal macrophages from mice treated with teicoplanin.

PMID- 9144843
TI  - Follicular and luteal progesterone synergize to maintain 5-day cyclicity in rats.
AB  - The length of the ovarian cycle in rat is determined by the duration of
      progesterone secretion from the corpora lutea (CL) during diestrus. The action of
      progesterone secretion from the preovulatory follicles on proestrus is also
      responsible for the cycle length in 4-day cyclic rats. To study whether
      follicular and luteal progesterone participate in the maintenance of 5-day
      cyclicity, the effects of the antiprogestagen RU486 (5 mg on proestrus or estrus)
      on estrous cycle length and on the serum concentrations of LH in 5-day cyclic
      rats and in 4-day cycle experimentally induced by the dopamine agonist CB154 (1
      mg on estrus) were investigated. Furthermore, serum concentrations of
      progesterone on the day of ensuing ovulation were measured to see whether
      activation of the CL function after treatment with RU486 had occurred. Both 5-day
      and CB154-injected rats had a 3-day estrous cycle after RU486 on proestrus, while
      RU486 on estrus shortened by 1-day the estrous cycle length in 5-day but not in
      CB154-injected rats. Basal serum concentrations of LH increased and the LH surge
      decreased after RU486 treatment in both cycle types. Serum concentrations of
      progesterone rose only in 5-day rats injected with RU486. These results indicate
      that the actions of both follicular and luteal progesterone synergize in
      maintaining the length of the estrous cycle in 5-day cyclic rats and that
      functionally active CL increase progesterone production only under the action of
      a complete surge of prolactin.

PMID- 9144844
TI  - Kidney ATPase response in seawater-transferred rainbow trout (Oncorhynchus
      mykiss). Effect of salinity and fish size.
AB  - Two sizes of domesticated rainbow trout (Oncorhynchus mykiss, 40 +/- 0.67 and 180
      +/- 3.9 g) were directly transferred to brackish water (9 ppt) and seawater (28
      ppt). Kidney Na(+)-K(+)-ATPase and Mg(2+)-ATPase activities were measured in
      fresh water, and after long-term seawater adaptation (up to 21 days). Renal Na(+)
      K(+)-ATPase activity increased after saltwater loading in small trout, while
      large trout displayed an unmodified ATPase activity. The smallest trout showed a
      low but progressive increase in renal Mg(2+)-ATPase activity after the transfer
      to both salinities. However, ATPase activity remained unchanged or significantly
      decreased in large trout after the transfer to seawater or brackish water,
      respectively.

PMID- 9144845
TI  - Changes in the hypothalamic serotonergic function may mediate the endocrine
      effects of melatonin.
AB  - The effects of a single injection of melatonin on serum thyroxine, corticosterone
      and prolactin levels, and the associated changes in the metabolism of serotonin
      (5-HT) in several hypothalamic regions of male rats kept under a 14-h light 10-h
      dark cycle (lights on at 08:00 h), are investigated. Melatonin (500
      micrograms/kg, s.c.) or replacing saline was injected at 18:00 h, and 8 animals
      from treated and control groups were killed 1 h (19:00 h), 12 h (06:00 h) and 18
      h (12:00 h) later. Melatonin significantly reduced serum thyroxine,
      corticosterone and prolactin levels within 1 h of treatment, indicating the
      existence of an acute inhibitory effect on hormonal secretion. Serum prolactin
      levels were increased 18 h after treatment, suggesting the implication of a
      different long-term regulatory mechanism. Injected melatonin induced several
      acute changes in the metabolism of 5-HT in the hypothalamus. Thus, a significant
      increase of 5-HT content in the preoptic area-anterior hypothalamic (POA-AH) and
      medial hypothalamic regions of melatonin-treated rats was observed within 1 h of
      treatment. The content of 5-hydroxyindoleacetic acid (5-HIAA) increased in medial
      hypothalamus, and the ratio 5-HIAA/5-HT decreased in POA-AH. The results show
      that melatonin acutely modifies the serotonergic activity in POA-AH and medial
      hypothalamus, and simultaneously inhibits thyroid, adrenal and pituitary hormonal
      secretion. The results are discussed suggesting that the hypothalamic
      serotonergic system could be an ideal mechanism underlying short-term melatonin
      effects on endocrine function.

PMID- 9144846
TI  - Is the post-lunch dip in sprinting performance associated with the timing of food
      ingestion?
AB  - To detect whether the drop in performance around lunch has any direct association
      with the time of food ingestion, a group of 8 sprinters were studied for 5
      consecutive Saturdays. On each testing day, the times achieved during 80 meter
      sprints performed at eight different times of the day separated by 2 hour
      intervals were recorded. The 1st and 4th testing days, had identical sleep and
      mealtime schedules, and were therefore considered "control days", while on the
      2nd and 3rd testing days the schedule was brought forward ("advanced") or
      backward ("delayed") by 2 hours respectively. On the 5th testing day the sleep
      wake cycle was brought forward 2 hours without changing the mealtime schedule. A
      post-lunch dip (PLD) was detected on all testing days although at different
      times. No significant differences in performance were observed between days 1 and
      4 while there were differences in performance during the other testing days. It
      is worth pointing out that PLD occurred at about 15:00 h on the control days,
      with significant differences between the 2nd (p < 0.05) and 3rd days (p < 0.05),
      and with the deterioration in performance starting at 15:00 h on the 3rd day
      despite the fact that lunch had been served at 16:00 h. In conclusion, PLD does
      not appear to be directly linked to the time of lunch, although lunch itself
      could potentiate its effects. It is also worth mentioning the fact that this
      deteriorating effect does not occur after any other meals of the day.

PMID- 9144847
TI  - Regulation of energy balance and adiposity: a model with new approaches.
AB  - Obesity etiology and treatment have been fraught with disappointment for
      researchers, because the mechanisms regulating fuel homeostasis and adiposity are
      incompletely understood. It can now be hypothesized in the light of new evidences
      that the control of body weight and composition depends upon an axis with three
      interrelated and self-controlled components: 1) food intake; 2) nutrient turnover
      and thermogenesis and 3) body fat stores, all of which underly complex feedback
      mechanisms. This approach considers two of the most relevant recent findings in
      the field (leptin and beta 3-adrenoceptors), adding new views to previous
      metabolic models of obesity. This perspective supplies some additional clues to
      the understanding of body composition regulation as well as the potential
      involvement of genetic and hypothalamic disorders in the onset of obesity.

PMID- 9144848
TI  - A potential new treatment for rheumatoid arthritis: thunder god vine.
AB  - Various extracts of the vinelike plant Tripterygium wilfordii Hook f have been
      widely used in China to treat patients with a number of autoimmune diseases.
      Although most of the clinical experience has derived from uncontrolled trials,
      one placebo-controlled double-blind trial has clearly demonstrated efficacy in
      rheumatoid arthritis. Studies in laboratory animals have indicated that extracts
      of Tripterygium wilfordii Hook f suppress both immune and inflammatory responses
      and also effectively treat a number of models of autoimmune disease. More
      detailed in vitro analysis has indicated that components of Tripterygium
      wilfordii Hook f suppress immune responses by inhibiting transcription of
      cytokine genes, including interleukin-2 and gamma interferon. The current status
      of knowledge of the potential clinical benefit of this herbal remedy and possible
      mechanisms accounting for its utility are considered in this review.

PMID- 9144849
TI  - Antiphospholipid antibodies: basic immunology and assays.
AB  - Great progress has been made within the past 10 years in characterizing,
      assaying, and describing mechanism(s) of action in vitro of antiphospholipid
      antibodies (a-PL Abs); three prominent members are reagin, anticardiolipin
      antibodies (a-CL Abs), and the lupus anticoagulants (LAC). The major focus of
      this review is on basic and current biochemical and immunologic research. First,
      the biochemistry, structural composition, and sources of anionic and dipolar
      ionic (zwitterionic) phospholipids are discussed together with several serum
      antibodies directed to these phospholipids. Cardiolipin, the most acidic
      phospholipid (net negative charge of 2 at pH 7.0) has been historically important
      as an antigen for testing reagin in syphilis serology, and currently is part of
      the antigenic composition used in the Venereal Disease Research Laboratory (VDRL)
      tests. In this connection, the chronic biological false-positive test for
      syphilis and the LAC are discussed in association with autoimmune disorders such
      as systemic lupus erythematosus. Second, a naturally occurring plasma
      anticoagulant in vitro and a critical cofactor for binding of purified autoimmune
      a-CL Abs to cardiolipin is considered, the beta 2-glycoprotein I (beta 2-gpI).
      This single-chain plasma polypeptide is highly glycosylated, has 326 amino acids,
      a molecular weight of 50 kD, and is characterized by repeating amino acid motifs
      or domains that structurally resemble multiple loops. The highly cationic C
      terminal fifth domain binds to anionic phospholipids. The beta 2-gpI is a member
      of the short consensus repeat superfamily of proteins, and is compared with other
      proteins with similar domains. Third, experiments are detailed for defining LAC
      and distinguishing it from other a-CL Abs. Cofactors are also associated with LAC
      and include beta 2-gpI, prothrombin, protein C, protein S, tissue factor, and
      factor XI. Thus, LAC antibodies are heterogeneous, and no individual assay can
      detect all LACs. Because patients with syphilis and other infectious diseases
      have no cofactor associated with a-CL Abs, their plasma LACs are negative. The a
      CL Abs found in infection are not associated with the clinical features of the
      antiphospholipid syndrome. LAC assays are important because of the pathogenetic
      association with clinical observations of venous and arterial thrombosis,
      thrombocytopenia, and recurrent fetal loss. Finally, reports leading to
      development of currently used direct solid-phase enzyme-linked immunosorbent
      assays (ELISA) for testing a-PL Abs are outlined; these developments have greatly
      increased understanding of the basic immunology of target antigens and their
      respective antibodies. Of significance, a-CL Abs cross-react with other anionic
      phospholipids. Additionally, the results of these assays led to the realization
      that high levels of circulating a-PL Abs over long periods are associated with a
      number of clinical problems now known collectively as the antiphospholipid
      syndrome.

PMID- 9144850
TI  - Clinical and subclinical alveolitis in connective tissue diseases assessed by
      bronchoalveolar lavage.
AB  - Subclinical alveolitis, as assessed by bronchoalveolar lavage (BAL) cell
      analysis, may be present in the lower respiratory tract of a high proportion of
      symptomless patients with connective tissue diseases (CTDs) with normal chest
      roentgenograms. The distribution of BAL cell types, mainly macrophages,
      lymphocytes, and polymorphonuclear neutrophils, varies according to type of CTD
      and to the presence of associated interstitial lung disease (ILD). Nevertheless,
      subclinical alveolitis can be classified into two major groups: lymphocyte and
      neutrophil alveolitis. A mixed, lymphocyte and neutrophil alveolitis may be
      detected as well. Subclinical alveolitis, particularly in systemic sclerosis,
      frequently is associated with abnormalities of lung parenchyma as assessed by
      computed tomography (CT) scan, supporting the hypothesis that it may be
      associated with the development of overt ILD. Close follow-up of these patients
      is needed to better determine whether subclinical alveolitis precedes ILD and
      whether early detection of subclinical alveolitis in CTDs may identify those
      patients who are at risk for the development of ILD in the future.

PMID- 9144851
TI  - A systematic review of randomized controlled trials of pharmacological therapy in
      osteoarthritis of the knee, with an emphasis on trial methodology.
AB  - We systematically reviewed randomized controlled trials (RCTs) of pharmacological
      therapy in knee osteoarthritis (OA), published between 1966 and August 1994. RCTs
      were identified by MEDLINE, supplemented by a manual search of reference lists.
      Qualitative assessment of RCTs was performed using Gotzsche's method; design and
      analysis features were rated on a scale of 0 (worst) to 8 (best). Heller et al's
      method was used to compare efficacy of nonsteroidal antiinflammatory drugs
      (NSAIDs) in comparative trials. A total of 80 RCTs were analyzed (45 involved
      NSAIDs, 3 analgesics, 5 intraarticular [IA] steroids, 9 biological agents,
      including IA hyaluronic acid, and 18 mixed modalities, including topical
      capsaicin). The median design and analysis scores for all 80 RCTs were 2 and 5,
      respectively. NSAIDs were superior to placebo in all short-term trials, but in
      the 32 comparative NSAID trials, only five (16%) found significant differences in
      efficacy. Heller et al's method identified differences in 14 NSAID comparisons;
      etodolac (600 mg/day) was superior in five of its nine comparisons. Indomethacin
      and aspirin were the most toxic NSAIDs. IA steroids were superior to placebo in
      short-term efficacy (< 1 month). Biological agents were superior to placebo and
      generally well tolerated over a mean follow-up of 48 weeks. Acetaminophen was
      superior to placebo and was comparably efficacious to low-dose naproxen and
      ibuprofen (< 2,400 mg/day). The data support the use of acetaminophen, topical
      capsaicin, IA steroids, IA hyaluronic acid, and NSAIDs in the treatment of
      patients with knee OA.

PMID- 9144852
TI  - Socioeconomic evaluation of rheumatoid arthritis and osteoarthritis: a literature
      review.
AB  - Limited resources and the need to improve the cost-effectiveness of medical
      procedures underlie the increasing importance of socioeconomic evaluations of
      health care. A search of MEDLINE was conducted to identify publications on the
      socioeconomic aspects of the two most important joint diseases: rheumatoid
      arthritis (RA) and osteoarthritis (OA). Analysis of the retrieved publications
      focused on three areas: (1) description of the socioeconomic effects of these
      diseases; (2) methodological approaches of the economic analyses; and (3)
      discussion from the perspective of patients, clinicians, or public health policy
      makers. Of 52 publications dealing with cost data for RA and OA, 44 presented
      original and recently collected and developed data. Twenty-six were classified as
      cost analyses, three as cost-benefit analyses, and 11 as cost-effectiveness
      analyses (four did not fit into any of these classifications). Eight established
      methodological criteria were used to test for "full economic evaluation"; none of
      the reviewed studies fulfilled all eight, and only one study fulfilled seven. The
      gap between the importance of the socioeconomic effects of RA and OA and the
      research conducted in this field is considerable. A quality standard could be
      developed to serve as a guideline for further research.

PMID- 9144853
TI  - Receptor imaging: competitive or complementary to antibody imaging?
AB  - Both radiolabeled ligands to specific receptors on cell surfaces and radiolabeled
      antibodies to specific cell surface epitopes provide new opportunities to
      scintigraphically identify tumors. Both radiolabeled ligands and antibodies are
      characterized by high orders of affinity for their respective binding sites and
      offer greater specificity over the agents previously used for tumor imaging
      including gallium 67, thallium 201, technetium 99m MIBI, and flourine-18-labeled
      deoxyglucose. The two classes of tumor-binding tracers differ primarily based on
      molecular weight although the nonspecific portion of the immunoglobulins are also
      antigenic. Increased molecular weight results in prolonged plasma survival, which
      increases the interval available for tumor permeation but also produces increased
      nonspecific background activity, which impairs image contrast. At the present
      time, encouraging clinical results have been obtained with both agent types, but
      further development is necessary. Receptor-ligand tracers provide better contrast
      than antibodies or antibody fragments. Receptor-ligand imaging technology awaits
      further developments in an understanding of the biology of receptor expression in
      normal tissue and tumors and improved radio-chemical techniques and pharmacology
      to define the radioligands of choice. Radiolabeled antibodies will probably
      evolve in the direction of increased use of antibody fragments and possibly the
      identification and polymerization of epitope-recognition units in order to
      provide high-affinity, nonantigenic, small molecular weight tracers that will be
      more permeable in tumors and clear more rapidly from background tissue. Rather
      than compete or complement each other, the techniques will likely produce a
      hybrid technology, radiolabeled molecular recognition units, with the better
      features of both technologies including high binding affinity (low dissociation
      constant) for surface membrane epitopes, including receptor sites.

PMID- 9144854
TI  - PET in oncology: will it replace the other modalities?
AB  - Medical imaging technology is rapidly expanding and the role of each modality is
      being redefined constantly. PET has been around since the early sixties and
      gained clinical acceptance in oncology only after an extreme number of scientific
      publications. Although PET has the unique ability to image biochemical processes
      in vivo, this ability is not fully used as a clinical imaging tool. In this
      overview, the role of PET in relation to other tumor imaging modalities will be
      discussed and the reported results in the literature will be reviewed. In
      predicting the future of PET, technical improvements of other imaging modalities
      need to be dealt with. The fundamental physical principles for image formation
      with computed tomography (CT), ultrasound (US), magnetic resonance imaging (MRI),
      photon-emission tomography (PET), and single photon emission CT (SPECT) will not
      change. The potential variety of radiopharmaceuticals which may be developed is
      unlimited, however, and this provides nuclear imaging techniques with a
      significant advantage and adaptive features for future biologic imaging. The
      current applications of PET in oncology have been in characterizing tumor
      lesions, differentiating recurrent disease from treatment effects, staging
      tumors, evaluating the extent of disease, and monitoring therapy. The future
      developments in medicine may use the unique capabilities of PET not only in
      diagnostic imaging but also in molecular medicine and genetics. The articles
      discussed in this review were selected from a literature search covering the last
      3 years, and in which comparisons of PET with conventional imaging were addressed
      specifically. PET studies with the glucose analogue fluorine-18-labeled
      deoxyglucose (FDG) have shown the ability of detecting tumor foci in a variety of
      histological neoplasms such as thyroid cancer, breast cancer, lymphoma, lung
      cancer, head and neck carcinoma, colorectal cancer, ovarian carcinoma, and
      musculoskeletal tumors. Also, the contribution of the whole body PET (WBPET)
      imaging technique in diagnosis will be discussed. In the current health care
      environment, a successful imaging technology must not only change medical
      management but also demonstrate that those changes improve patient outcome.

PMID- 9144855
TI  - Diagnostic bone scanning in oncology.
AB  - Over the last several decades bone scanning has been used extensively in the
      evaluation of oncology patients to detect bone involvement. It can provide
      information about disease location, prognosis, and the effect of therapy. Bone
      scanning offers the advantages of whole body evaluation and the detection of
      lesions earlier than other techniques. However, as newer diagnostic tools become
      available, indications for bone scanning must be revised and the results combined
      with these other tests in order to provide optimum patient care. Advances in
      instrumentation and the subsequent improvement in image quality have allowed
      nuclear medicine physicians to provide more accurate bone scan interpretations.
      By optimizing image acquisition, it is often possible to determine lesion
      characteristics, which are more likely to represent malignancy. Knowledge of
      disease pathophysiology and other specific properties of the patient's primary
      tumor, along with subsequent correlation of scan abnormalities to patient
      history, physical examination, previous studies, and other radiological
      examinations, is essential for determining lesion significance. The differential
      diagnosis of a scan abnormality should also include consideration of both false
      normal and abnormal causes. The final interpretation should be clearly
      communicated to the clinician with appropriate recommendations for further
      evaluation. Only through careful attention to the patient, the clinician, and
      appropriate study acquisition parameters will bone scanning maintain its place in
      the evaluation of oncology patients.

PMID- 9144856
TI  - Oncologic imaging: interactions of nuclear medicine with CT and MRI using the
      bone scan as a model.
AB  - There are many radionuclides currently used in oncologic imaging including
      technetium 99m diphosphonates, gallium 67, thallium 201, technetium 99m
      sestamibi, and others. The specific interactions of each of these agents with
      computed tomography (CT) and magnetic resonance imaging (MRI) are extensive. The
      radionuclide bone scan using 99mTc diphosphonate is the most frequently performed
      nuclear medicine examination in oncologic imaging. The bone scan can be used as a
      model to generalize the interactions of nuclear medicine with CT and MRI. The
      applications for the bone scan and many other nuclear medicine procedures in
      oncologic imaging include evaluating for metastases, assessing the response to
      therapy, and guiding radiation therapy planning. Bone scan findings that are
      equivocal for metastases can be evaluated with other imaging modalities. Areas of
      abnormal uptake in the axial skeleton can be evaluated with CT or MRI, whereas
      those in the appendicular skeleton can be evaluated with plain radiographs,
      followed by CT or MRI if necessary. The bone scan is valuable in oncologic
      imaging because of its high sensitivity for lesion detection, its ease in whole
      body imaging, and its low cost. The major disadvantage of the bone scan is that
      it lacks fine anatomic detail, which is of particular importance in the cancer
      patient with local back pain, radiculopathy, or myelopathy. Because local back
      pain with or without radiculopathy is the earliest symptom of spinal cord
      compression in 90% of patients, an MRI is the study of choice because of its
      exquisite depiction of anatomy. A myelogram followed by a postmyelogram CT can be
      performed if there are contraindications to an MRI. The basic principle of high
      sensitivity for lesion detection and ease in whole body imaging provided by
      nuclear medicine and fine anatomic detail provided by CT and MRI can be applied
      also to the use of other radionuclides in oncologic imaging.

PMID- 9144857
TI  - The changing role of radioiodine in the management of differentiated thyroid
      cancer.
AB  - This article discusses several aspects of the evaluation and management of
      differentiated thyroid carcinoma that are changing or may change in the near
      future. Although conventional treatment of this disease is highly effective, some
      modification may improve the welfare of patients and the overall results. Because
      the symptoms of hypothyroidism are vexing, there has been great interest in using
      recombinant human thyroid-stimulating hormone (rhTSH) to prepare patients for
      iodine 131 imaging. rhTSH has been about as effective as thyroid hormone
      withdrawal for diagnostic imaging so that approval for this use is expected.
      Another topic of interest is the administration of 131I therapy to patients whose
      serum thyroglobulin levels are abnormal but whose diagnostic 131I scans are
      negative. Because the 131I scans after therapy are often abnormal in these
      patients and a reduction of serum thyroglobulin can occur, this approach seems
      effective. The long-term impact of this therapy on recurrence and survival,
      however, is unknown. A third issue that is currently under review is the amount
      of 131I that should be used for diagnostic scanning. Although past opinion
      favored larger doses, "stunning" of thyroid remnant and tumor can occur with
      diagnostic 131I imaging. Substituting iodine 123 is an alternative for
      postthyroidectomy scanning, but when administered as 300 uCi it is less accurate
      than 131I for recurrent disease or distant metastases. Related to these issues,
      two other topics are reviewed: the use of other radiopharmaceuticals for imaging
      patients with thyroid cancer, and 131I dosimetry.

PMID- 9144858
TI  - Unsealed source therapy of painful bone metastases: an update.
AB  - Pain in patients with cancer metastatic to bone is a significant cause of
      morbidity and of referrals from general practice and specialist physicians.
      Management typically utilizes radiation therapy and the graduated use of opiate
      analgesics. Bone-seeking radiopharmaceuticals have provided a new option to these
      management strategies, which is effective and cost effective. Strontium 89 is now
      in routine clinical use, while rhenium 186 hydroxyethylidene diphosphonate (HEDP)
      and samarium 153 ethylenediaminetetramethylene phosphonate (EDTMP) are in Phase
      III trials and tin 117m (4+) diethylene triaminepentacetic acid (DTPA) is in
      Phase I trials. Evidence taken primarily from the Strontium 89 trial, shows
      unsealed source therapy with these bone-seeking radiopharmaceuticals to be
      effective in palliating pain, improving quality of life, reducing the rate at
      which new painful sites develop, reducing requirements for additional radiation
      therapy, and reducing lifetime management costs. Indications and
      contraindications to therapy have now been defined, and retreatment is an option
      with all radiopharmaceuticals.

PMID- 9144859
TI  - Reverse ventilation/perfusion mismatch.

PMID- 9144860
TI  - False-positive myocardial perfusion scintigraphy in syndrome X.

PMID- 9144862
TI  - Dendritic cells of the gastrointestinal tract.

PMID- 9144861
TI  - Abnormal skull uptake on bone scan.

PMID- 9144863
TI  - The immunopathology of M cells.

PMID- 9144864
TI  - The intestinal epithelial cell: immunological aspects.
AB  - IECs likely play an important role in immunological defense mechanism. Apart from
      being a passive barrier against luminal bacteria, IECs secrete protective and
      microbiocidal products such as ITF, complement components and cryptdins into the
      lumen. Moreover, IECs produce secretory component that is essential for the
      transport of IgA from the lamina propria into the lumen. IECs also have
      regulatory functions. They express adhesion molecules important in the homing of
      T cells and other leukocytes, and likely modulate T cell functions in a paracrine
      way. Furthermore, IECs secrete cytokines, either constitutively or after
      bacterial challenge, and they express cytokine receptors. Lastly, IECs may play
      an important role as non-professional antigen-presenting cells by expressing
      classical MHC class I and class II and nonclassical MHC class I molecules on the
      cell surface. This aspect is particularly intriguing in that IECs also express a
      FcR that may have a function in luminal antigen sampling.

PMID- 9144865
TI  - On the front lines: intraepithelial lymphocytes as primary effectors of
      intestinal immunity.

PMID- 9144866
TI  - A T cell/B cell/epithelial cell internet for mucosal inflammation and immunity.

PMID- 9144867
TI  - Immunopathology of Helicobacter pylori infection and disease.

PMID- 9144868
TI  - Immunopathology of human immunodeficiency virus infection in the gastrointestinal
      tract.

PMID- 9144869
TI  - Immunopathology of gluten-sensitive enteropathy.

PMID- 9144870
TI  - Immunopathology of human inflammatory bowel disease.

PMID- 9144872
TI  - Transportation dose and doses to extracranial sites during stereotactic
      radiosurgery with the Leksell Gamma knife.
AB  - Two dosimetric aspects of Leksell Gamma knife (LGK) treatment have been
      investigated in this study: (a) measurement of the small dose (transportation
      dose) which is absorbed during the patient's transportation into and out of the
      treatment position within the ionization chamber, and (b) measurements of the
      doses absorbed by the eyes, thyroid, breast, abdomen, gonads, knee and ankle
      during the treatment using thermoluminescent dosimetry (TLD). The transportation
      dose was 0.253 +/- 0.003 Gy, which represented 8.4% of the dose rate (3.005
      Gy/min) during measurements. In vivo TLD measurements have been performed on 51
      patients. The doses measured in organs and sites of interest were 0.223 +/- 0.168
      Gy for the eyes, 0.081 +/- 0.050 Gy for the thyroid, 0.049 +/- 0.033 Gy for the
      breast, 0.024 +/- 0.18 Gy for the abdomen, 0.012 +/- 0.008 Gy for the gonads,
      0.003 +/- 0.002 Gy for the knee and 0.002 +/- 0.002 Gy for the ankle. During LGK
      radiosurgery, doses to extracranial sites and organs depend mainly on the total
      target dose and the number of shots used for the treatment. These doses are
      generally low; the maximum dose was measured for the eyes (approximately 0.7% of
      the maximum target dose), and the doses to other body organs decrease with
      increasing distance from the isocenter of the LGK radiation unit.

PMID- 9144871
TI  - Electrical stimulation of the globus pallidus preceding stereotactic
      posteroventral pallidotomy.
AB  - Physiological methods such as microelectrode recording of neuronal activity and
      electrical stimulation of target structures can improve the safety and efficacy
      of certain stereotactic surgeries. The globus pallidus (GP) was electrically
      stimulated in 136 patients with Parkinson's disease prior to unilateral
      posteroventral pallidotomy to identify functional areas and prevent deficits. We
      found that electrical stimulation of the GP elicited two principal responses:
      contractions of the contralateral hand and flashing lights. The mean voltage that
      evoked motor responses was 4.3 V (range 1.7-9.0 V), while higher intensity was
      necessary to elicit visual responses (mean 6.8 V; range 3.5-9.9 V). Contralateral
      tremor, speech impairment, paresthesias, and warm sensations were also elicited.

PMID- 9144874
TI  - Use of magnetic resonance imaging in stereotactic surgery. A survey of members of
      the American Society of Stereotactic and Functional Neurosurgery.
AB  - Members of the American Society of Stereotactic Functional Neurosurgery were
      surveyed to determine the current use of magnetic resonance imaging (MRI) for
      stereotactic coordinate determination. Of 137 respondents, 48% used MRI as the
      sole technique for some biopsy procedures. Of those performing functional
      surgery, more surgeons use MRI alone than CT alone for localization. Of those
      surgeons who used MRI alone for stereotactic surgery, 98.6% were satisfied with
      this method. Significant factors related to the use of MRI amongst individual
      surgeons included the performance of > or = 2 stereotactic surgeries per week,
      the performance of radiosurgery, and being in an academic practice (p < 0.0004).
      The increasing use of MRI in stereotactic surgery must be coupled with quality
      assurance testing from frame manufacturers, imaging manufacturers, and surgeons.

PMID- 9144873
TI  - Cerebral blood flow velocities and trigeminal ganglion stimulation. A
      transcranial Doppler study.
AB  - Transcranial Doppler sonography (TCD) patterns of middle cerebral arteries (MCA)
      were recorded in 10 patients before and during unilateral trigeminal ganglion
      stimulation (TGS). During TGS, TCD flow velocity significantly decreases in all
      patients: on both sides in 2 patients, only ipsilaterally to the TGS in 7
      patients, and only on the opposite side in the remaining patient. In 2 patients,
      a controlled progressive hypercapnia test was performed before and during TGS. An
      enhanced vascular response to increased CO2 concentrations was observed during
      TGS.

PMID- 9144875
TI  - Long-term outcome of iontophoresis treatment for torticollis.
AB  - In 1969, a patient with torticollis was successfully treated by a procedure
      called iontophoresis. Between 1958 and 1972 223 patients with torticollis were
      treated with this procedure. 88 of these patients (39%) were located and 56 (25%
      of the total, 64% of those located) returned a survey regarding their condition.
      28 (13% of the total, 32% of those located, 50% of those responding) enjoyed an
      initial period of improvement. Of these, 16 patients (7% of the total, 18% of
      those located, 29% of those responding, 51% of those with initial improvement)
      reported sustained improvement through the time of the survey. However, 5 of
      these patients had additional treatment with botulinum toxin or selective
      denervation. We conclude that the long term effectiveness of iontophoresis
      treatment in the course of torticollis is minimal.

PMID- 9144876
TI  - Expression of transforming growth factor-beta receptor type I and type II in rat
      ventral prostate and Dunning R3327 PAP adenocarcinoma in response to castration
      and oestrogen treatment.
AB  - In the normal prostate, transforming growth factor-beta 1 (TGF-beta 1) inhibits
      epithelial cell growth and is associated with apoptosis. The role of TGF-beta 1
      in prostate cancer remains, however, unclear. In this work, the expression of TGF
      beta receptor type I and II (TGF beta-RI and TGF beta-RII) in the Dunning R3327
      PAP adenocarcinoma was studied, after castration and oestrogen treatment. Since
      castration induces apoptosis in the rat ventral prostate (VP) [21], but not in
      the Dunning R3327 PAP tumour [46], the TGF-beta receptor levels in the tumour
      were compared to the receptor levels in the VP. Methods used were competitive
      reverse transcription-polymerase chain reaction (RT-PCR) and
      immunohistochemistry. In the VP, TGF beta-RI and TGF beta-RII expressions were
      increased after castration, indicating a negative regulation of TGF beta
      receptors by androgens. In the Dunning tumour, TGF beta-RI and TGF beta-RII
      levels were elevated and only TGF beta-RI showed a clear-cut increase after
      castration. The receptors were located in epithelial and smooth muscle cells in
      the VP and mainly in epithelial cells in the Dunning tumour. In conclusion, the
      elevated TGF beta receptor levels and the diminished androgen regulation of TGF
      beta-RII in the tumour distinguish the Dunning R3327 PAP tumour from the normal
      prostate and need to be further elucidated.

PMID- 9144877
TI  - Endopeptidase 24.11 activity in the human prostate cancer cell lines LNCaP and
      PPC-1.
AB  - Human endopeptidase 24.11 (EP) occurs in greatest abundance on terminally
      differentiated prostate cells; thus, loss of EP could mark dedifferentiation of
      prostate epithelium. To identify laboratory models that would permit continuous
      work on the biochemistry and hormonal regulation of EP, we examined the well
      differentiated LNCaP and poorly differentiated PPC-1 human prostate cancer cell
      lines. Ultrastructural analysis revealed that LNCaP secretes electron-dense
      material that resembles the particulate matter of seminal plasma, which is
      associated with endopeptidase activity. LNCaP medium contained EP activity while
      PPC-1 medium did not. Whether the apparent deletion of EP from the PPC-1 cell
      line is characteristic of poorly differentiated prostate adenocarcinoma is not
      yet clear. However, it may be relevant to the carcinogenic process that EP can
      limit growth of lung small carcinomas by inactivating cell growth-promoting
      bombesin-like peptides. Because bombesin has been identified in aggressive human
      prostate cancers, loss of EP in PPC-1 could represent a necessary step in
      transformation to aggressive phenotype. The combination of LNCaP and PPC-1, which
      offers well-differentiated and poorly differentiated cancer phenotypes, appears
      well suited to studying the relevance of EP in prostate cancer biology.

PMID- 9144878
TI  - Immunostimulation in the urinary bladder by local application of Nocardia rubra
      cell wall skeleton preparation (Rubratin) for superficial bladder cancer
      immunotherapy--a phase I/II study.
AB  - OBJECTIVES: Twelve patients with superficial papillary transitional cell
      carcinoma of the bladder (pTa, pT1) were treated with six consecutive weekly
      intravesical instillations of Rubratin (in a dose of 1.5, 3.0, or 4.5 mg), a cell
      wall skeleton preparation of Nocardia rubra (NCW). The main objective of this
      study was to look for local immunomodulating effects of NCW and in the first four
      patients the effect on a marker lesion was also investigated. METHODS: Local
      immunostimulation in all 12 patients was determined by (1) measurement of
      cytokine induction [interleukin 1 beta (IL1 beta), IL2, IL6, and tumor necrosis
      factor alpha (TNF alpha)], (2) leukocyte influx into the urine, and (3)
      phenotypic analysis of the lymphocyte fraction of these leukocytes. RESULTS:
      Significantly elevated levels of Rubratin-induced IL1 beta (P < 0.001), IL2 (P <
      0.001), IL6 (P < 0.01), and TNF alpha (P < 0.001) were found compared to control
      pretherapy levels. Rubratin also induced leukocyte influx into the urine.
      Fluorescence-activated cell sorter (FACS) analysis of the urinary leukocytes
      indicated T-cell activation (IL2 receptor and HLA-DR expression), while in two
      out of five patients the CD4/CD8 ratios were increased. Urinary cytokine
      induction by Rubratin was comparable with cytokine induction observed in
      nonresponding bacillus Calmette-Guerin (BCG) patients (recurrent tumor within 6
      months), but less compared with responding BCG patients (no recurrent tumor
      within 6 months). Clinical results showed no response on the marker lesion and in
      five out of eight patients early recurrence was found after complete
      transurethral resection (TUR) of the bladder tumors. This biological response
      modifier caused no local or systemic side effects at the doses used. CONCLUSION:
      Although local immunostimulation by intravesical Rubratin administration can be
      induced, the amount of immunocompetent cells attracted to the bladder is not as
      high as observed in BCG-responding patients, resulting in lower amounts of
      cytokines produced. This could also explain the lack of clinical efficacy.

PMID- 9144879
TI  - Detection of vital germ cell tumor cells in short-term cell cultures of primary
      tumors and of retroperitoneal metastasis--clinical implications.
AB  - By establishing short-term cell cultures derived from retroperitoneal metastasis
      after neoadjuvant chemotherapy, our aim was to improve the diagnosis and
      prognosis in patients with advanced testicular germ cell tumors. The histological
      evaluation of surgically removed metastatic tissue by retroperitoneal
      lymphadenectomy (RLA) is extremely complicated after previous chemotherapy, but
      knowledge of persistence of vital tumor cells in residual lesions is of great
      prognostic value and therapeutic consequence in patients with testicular germ
      cell tumors. We therefore investigated whether vital tumor tissue could be
      detected in short-term cell cultures derived from such metastatic lesions by
      measuring the concentration of the tumor markers beta human chorionic
      gonadotropin (beta HCG) and alpha-1 fetoprotein (AFP) in cell culture
      supernatants. We initially demonstrated the specificity of the determination in
      cell cultures of human transitional-cell carcinoma cell lines, human foreskin
      fibroblasts and normal testicular tissue. In a group of 20 patients with
      untreated primary testicular germ cell tumors, detection of beta HCG and AFP was
      increased about threefold in cell culture supernatants in comparison to the serum
      concentration. Finally, we prepared primary cell cultures from surgically removed
      retroperitoneal metastasis of 12 patients with testicular germ cell tumors after
      chemotherapy. The serum concentrations of beta HCG and AFP of all patients were
      at normal values when RLA was performed. However, pathologically increased
      concentrations of beta HCG (3/3) and AFP (2/3) in cell culture supernatants were
      found in 3 of 12 cell cultures. Interestingly, these three patients with a
      pathological increase in beta HCG and AFP as determined in the supernatant of the
      short-term cell cultures had tumor progression within a mean follow-up of 3 +/- 1
      months (P < 0.01), whereas 9 of 12 patients who had no pathological increase in
      beta HCG and AFP as determined in the supernatant of the short-term cell culture
      were in complete remission (CR) after a mean follow-up of 40 +/- 11.6 months.

PMID- 9144880
TI  - Uptake and intracellular distribution of idarubicin in secondary cultures of
      normal and neoplastic urothelium.
AB  - This study analyzes the uptake and endocellular distribution of idarubicin (IDA)
      in normal and neoplastic urothelial secondary cultures in relation to the changes
      in concentration and time of exposure. The urothelial lines were isolated by
      Freshney's method from biopsy fragments taken from five patients with superficial
      bladder cancer. Pharmacological experiments were carried out on subcultures
      previously immunophenotypically characterized and did not exceed ten passages.
      The uptake and endocellular distribution of IDA was analyzed by densitometric
      image analysis on cells treated for 10, 20, 30 and 60 min and 2 h with scalar
      dosages from 10 ng/ml to 2430 ng/ml. Microscopic observations and densitometric
      analyzes revealed that in the cells treated with IDA, fluorescence was higher in
      the cytoplasm compared to the nucleus and increased with the change in dosage.
      Moreover, densitometric data showed that IDA uptake in the first 20 min was
      higher in the neoplastic cells, but after that period its behavior became
      heterogeneous at 30 and 60 min, while at 2 h there was an inversion of the trend.
      These results suggest that the in vitro cytotoxicity should be evaluated in order
      to verify whether the elevated uptake of IDA in the first 20 min of treatment is
      really correlated to a more elevated toxicity in the neoplastic cells with
      respect to the normal cells. This is presently under investigation.

PMID- 9144881
TI  - Experimental assessment of ureteral free autograft.
AB  - OBJECTIVE: To establish the sequence of ureteral events under ischemic and
      desvascularized conditions but without immunologic interference. MATERIALS AND
      METHODS: Sixty-two rats were divided into four groups. NU group (n 20) control
      group, normal ureter; SC group (n 15) only surgical control ureterolysis; NIAFG
      group (n 13) ureter used as non integrated autologous free graft; IAFG group (n
      14): ureter used as integrated autologous free graft. Urographic, histologic and
      histomorphometric studies were performed. RESULTS: We established ureteral
      changes in the NIAFG and IAFG groups, compared to the control groups (NU, SC).
      Surgical findings and urographic assessment revealed normal peristalsis with no
      ectasia in some cases, and no ureteral fistulas or extravasations were found in
      the IAFG group. Histologic findings showed preservation of the architecture of
      the three normal layers. Histomorphometric studies showed that ureterolysis
      caused edema in the lamina propria, while changes in ureter free graft depended
      on whether the ureter was integrated or not. In the NIAFG group only the
      urothelial layers showed differences and in the IAFG group the ureteral wall
      appeared thicker. Histomorphometric studies showed preservation of the normal
      histologic structures in all cases. CONCLUSIONS: The rat ureter can be used as a
      free autologous graft and represents an experimental model for immunologic
      events. We may assume that the necrosis and fibrosis observed in transplanted
      ureters are secondary to rejection in some cases.

PMID- 9144882
TI  - Reconstructive surgery of the urethra: a pilot study in the rabbit on the use of
      hyaluronan benzyl ester (Hyaff-11) biodegradable grafts.
AB  - We investigated the outcome of reconstructive surgery of the urethra through
      guides composed of a novel biodegradable and highly biocompatible polymer, Hyaff
      11. A tract of about 1.5 cm of the rabbit pendulous urethra was totally resected
      and replaced by a Hyaff-11 tubular graft. Eleven animals were analysed at each of
      the time points ranging from 7 days to 4 weeks following surgery. Histological
      and radiological evaluation showed a satisfactory remodelling of the neo-urethra
      around the implant. The regenerated connective tissue connected both urethral
      stumps within the first 7 days. On postoperative week 3, the Hyaff-11 guide had
      disappeared. At the 4-week time point the retrograde urethrogram showed a good
      distensibility of the neourethra. The regenerated stroma consisted of
      fibroblastic cells, and collagenous and elastic fibres. The neo-epithelium was
      pluristratified and exhibited cells of the cuboidal type.

PMID- 9144883
TI  - Effect of pentoxifylline on veno-occlusive priapism-induced corporeal tissue
      lipid peroxidation in a rat model.
AB  - OBJECTIVE: To investigate whether pentoxifylline could play a role in attenuation
      of the hazardous effects of ischemia/reperfusion on corporeal tissue in a rat
      model of veno-occlusive priapism (VOP). MATERIALS AND METHODS: Placebo and
      pentoxifylline were given to eight groups of rats prior to priapism being induced
      by a vacuum constrictive device for durations of 6 and 12 h, respectively. Half
      of the groups of rats that underwent the same duration of priapism (ischemic)
      were subjected to 1 h of detumescence after band removal (reperfusion). One group
      underwent no manipulation and no drug administration and served as a baseline
      determination (control). Corporeal homogenates were examined for lipid
      peroxidation (LP) derived malondialdehyde (MDA) accumulation via thiobarbituric
      acid assay. RESULTS: MDA concentration differed significantly between VOP rats
      and controls (P < 0.001) but did not differ significantly between ischemic-only
      groups and reperfused groups (P < 0.05). In the pentoxifylline-pretreated groups,
      although MDA accumulation tended to be slightly lower than in the placebo groups,
      the difference was not statistically significant (P < 0.05) either in the 6- or
      12-h duration priapic groups. CONCLUSIONS: LP, an indicator of radical oxygen
      metabolite (ROM) induced injury, occurs in rat corporeal tissue during and after
      abolishment of VOP. Single-dose pentoxifylline pretreatment failed to exert a
      protective effect on corporeal tissue in a rat model of VOP in terms of
      attenuation of LP.

PMID- 9144884
TI  - Effects of ultraviolet light on the tension of isolated human cavernosal smooth
      muscle from non-diabetic and diabetic impotent men.
AB  - The effects of ultraviolet (UV) light (310 nm) on human cavernosal smooth muscles
      were investigated. Cavernosal strips were obtained from men during penile
      prosthetic surgery. When the cavernosal strips were irradiated with UV light in
      an organ bath, after precontraction by norepinephrine (100 nM) for 10, 20, 40 and
      90 s at intervals of 3 min, the contracted cavernosal smooth muscles from the
      impotent men without vascular risk factors (controls) showed relaxation depending
      on the duration of irradiation. However, the relaxation was not found when the
      strips were pretreated with methylene blue (10 microM) or their epithelia were
      denuded. The relaxation response of the cavernosal strips from the patients with
      diabetogenic impotence was significantly reduced compared with that of the
      controls. Photorelaxation of human cavernosal strips therefore seems to be
      dependent on endothelium.

PMID- 9144885
TI  - Estimated levels of supersaturation with calcium phosphate and calcium oxalate in
      the distal tubule.
AB  - Approximate estimates of the ion-acitivity products of calcium phosphate and
      calcium oxalate in distal tubular urine were derived from the 16-h urinary
      excretion of calcium, oxalate, citrate, magnesium and phosphate. Urine variables
      were obtained from 96 normal subjects and 277 calcium stone formers and the
      calculations were carried out with iterative approximation using the EQUIL2
      program. With respect to other ions of importance for the ion-activity products,
      the urine was assumed to have a fixed composition with pH 6.45. Significantly
      higher ion-activity products of both calcium phosphate and calcium oxalate were
      recorded in stone formers. It was concluded that diurnal variations in urine
      composition and pH might result in peaks of calcium phosphate supersaturation in
      distal tubular urine whereby a crystallization can occur. In association with
      abnormalities in terms of promotion and inhibition of calcium salt
      crystallization, such a precipitation can be of importance for the subsequent
      formation of calcium renal stones.

PMID- 9144886
TI  - Prostate cancer: are we under the lee?

PMID- 9144887
TI  - Screening for prostate cancer.
AB  - Over the past few decades it has become clear that prostate cancer is a serious
      health problem in elderly men. The population of most Western countries is ageing
      and the number of deaths from prostate cancer patients is increasing. The most
      promising way to deal with this problem seems to be through early detection of
      the disease, which can be accomplished through case finding and screening of the
      male population at risk. The basic purpose of screening for a given disease is to
      separate from a large group of apparently healthy individuals those who have a
      high probability of having the disease under study. These individuals may be
      given a diagnostic workup, and if the diagnosis is established they can be
      brought to treatment. The concept of prostate cancer screening, however, is an
      extensively debated issue. The limited knowledge of the natural history,
      uncertainties about the effectiveness of treatment in reducing mortality and the
      adverse effects of treatment lead to fear of overdiagnosis and subsequent
      overtreatment. Routine application of screening for prostate cancer should not
      take place before the results of multicentre prospective randomised studies
      demonstrate a reduction in prostate cancer mortality through screening of the
      male population.

PMID- 9144888
TI  - Neo-adjuvant hormonal therapy of prostate cancer.
AB  - At present, only locally confined carcinoma of the prostate can be cured if all
      of the tumor tissue can be removed by surgery [36]. Early detection strategies
      using serum prostate-specific antigen (PSA), digital rectal examination (DRE) and
      transrectal ultrasound (TRUS) have been increasingly used. However, exact
      clinical determination of the local tumor extension is only possible to a limited
      extent [4, 13, 28, 34]. Up to 60% of clinical locally confined tumors are
      understaged after histopathological examination of the radical prostatectomy
      specimen. Furthermore a high incidence of positive margins of up to 60% has been
      reported [7, 21]. Although a clear surgical margin does not exclude local or
      distant disease recurrence, it is regarded as a good prognostic factor [3, 25].
      Androgen withdrawal prior to radical prostatectomy is an attractive theoretical
      option to decrease the risk of disease recurrence, since tumor regression can be
      induced by any procedure that reduces the intracellular concentration of
      dihydrotesterone by more than 80%. The benefit of preoperative medical androgen
      deprivation is controversial [6-8, 13, 15-17, 20, 23, 35, 37]. A priori a benefit
      would not be expected in any case if androgen withdrawal had no effect on the
      tumor. We therefore investigated the effects of a neo-adjuvant androgen-ablative
      therapy (NAT) in a large population of 375 patients who underwent radical
      retropubic prostatectomy (RRP) after NAT. We report in particular the effects of
      NAT on prostate volume measured by TRUS, PSA, clinical stage and tumor morphology
      including positive surgical margins. Furthermore the recently reported first
      results of prospective randomized trials comparing RRP alone versus NAT plus RRP
      are discussed to analyze the possible impact of NAT.

PMID- 9144889
TI  - Intermittent androgen deprivation in advanced prostate cancer.

PMID- 9144890
TI  - The antiandrogen withdrawal syndrome.
AB  - In 1989 the unanticipated agonist effect of antiandrogens on LNCaP prostate
      cancer cells was detected. A "flutamide withdrawal syndrome" was first described
      by Kelly and Scher [15], who reported a decrease in serum prostate-specific
      antigen (PSA) levels after the removal of flutamide from the treatment regimen.
      In the last few years the paradoxical response to antiandrogens has also been
      reported for bicalutamide, chlormadinone acetate and others. Therefore the name
      of the syndrome has changed to "antiandrogen withdrawal syndrome." Several
      reasons such as mutations in the androgen receptor or a direct stimulatory effect
      of the antiandrogen for this effect have been discussed, but the exact molecular
      mechanism remains unclear. However, in patients with hormonally relapsed prostate
      cancer, a trial of "withdrawal therapy" is required prior to the initiation of
      toxic therapies.

PMID- 9144891
TI  - Second-line treatment of metastatic prostatic carcinoma.
AB  - Second-line palliative treatment of patients who have failed hormone therapy for
      advanced prostate cancer remains an important challenge in this disease. Very few
      agents have been shown to have a positive impact on survival, and toxicity is
      often therapy limiting in this elderly group of patients. Improvements in pain
      and performance status with maintenance of a reasonable functional status are
      worthwhile goals of any therapy at this stage. The earlier diagnosis of
      progressive disease from a rising prostate-specific antigen (PSA), and the use of
      validated quality of life questionnaires, can lead to useful improvements in the
      quality of the lives of these patients whose quantity we cannot at present
      lengthen.

PMID- 9144892
TI  - Quality of life in patients with prostatic carcinoma: a review and results of a
      study in N+ disease. Prostate-specific antigen as predictor of quality of life.
AB  - Clinical evaluation in oncology has typically focused on outcome indicators,
      while less attention has been paid to how treatment affects quality of life (QOL)
      of the patient. In this article some general aspects of quality of life are
      discussed, a short review of published data on QOL in patients with prostate
      cancer is given and results of a QOL study executed by the authors on patients
      with lymph node positive prostatic cancer are presented. The purpose of the study
      was to examine the impact of immediate or delayed treatment (after objective
      progression) in patients with prostatic carcinoma (T1-3 N1-3 M0) on quality of
      life parameters. To this end an extended questionnaire was constructed. Fifty
      five patients participated. Assessment was performed twice, in 1994 and 1995. The
      comparison between patients with and patients without treatment showed in 1994 as
      well as in 1995 significant differences for hormonal treatment side effects such
      as sexual functioning and hot flushes, all of which were experienced more
      frequently by treated patients. In 1994 the treated patients experienced more
      psychological distress while in 1995 they showed worse physical function, less
      energy and more fatigue when compared to patients under surveillance. The premise
      that active treatment would improve the psychological quality of life was not
      sustained. In addition global health status and quality of life were identified
      as independent factors for progression in untreated patients with lymph node
      positive prostate cancer. Finally, an increase in prostate-specific antigen (PSA)
      in hormonally treated patients not only indicated hormonal escape but also a
      decrease in QOL.

PMID- 9144893
TI  - Role of proteoglycans in cell adhesion of prostate cancer cells: from review to
      experiment.
AB  - Development and progression of prostate cancer is a multistep process of
      cumulative genetic damage, acquired during a life-time. However, the altered
      genotype acts against an appropriate background of epigenetic control mechanisms.
      Several mechanisms of mitotically heritable, epigenetic control of differential
      gene transcription have been noted, such as stromal-epithelial and cell-cell
      interactions. In prostate cancer, an important, supporting and/or inhibiting role
      of stromal-epithelial interaction has been implicated in tumor growth,
      angiogenesis and metastasis, which includes cell proliferation, adhesion and
      motility. Within these processes, data mainly obtained in systems other than the
      prostate have shown a crucial (regulatory) role of proteoglycans (PGs) acting at
      the level of cell-cell and cell-pericellular matrix interactions. Although little
      information has been recorded from normal, benign hyperplastic and malignant
      prostate tissue, PGs are components of both the cell surface and the
      extracellular matrix (ECM) that form associations with other molecules, such as
      fibronectin and laminin. On the basis of cell-ECM adhesion/interaction as a
      prerequisite for both cell proliferation and motility, and the involvement of
      PGs, the purpose of this study was to investigate the possible biological
      relevance of (free) glycosaminoglycans (GAGs), as major functional substructures
      of PGs, on cell adhesion of a series of human prostatic cell lines cultured in
      vitro. The effects of a series of exogenously applied GAGs on cell adhesion and
      proliferation were studied in the human cell lines LNCaP, DU 145 and PC-3,
      cultured on tissue culture plastic as substratum. The applied GAGs were the
      natural GAGs heparin, heparan, dermatan, chondroitin-4 and chondroitin-6 sulfate,
      and the semisynthetic, GAG-like pentosan polysulfate (PPS). Addition of GAGs (1
      300 micrograms/ml) to cultures that were allowed to adhere for 24 h prior to GAG
      addition did not affect cell proliferation. In contrast, whereas the natural GAG
      added during cell adhesion had no effect. PPS strongly inhibited proliferation of
      LNCaP and DU145, but not the less anchorage-dependent PC-3 cells. Under the
      latter conditions, after 6 days of culturing the IC50 of proliferation were
      determined to be < 1 and 50 micrograms PPS/ml for LNCaP and DU145, respectively,
      corresponding with a profound effect on cell morphology. Direct measurements of
      cell adhesion confirmed that, in contrast to the natural GAGs, PPS inhibited cell
      adhesion. In conclusion, the interference of a nonnatural, GAG-like structure
      with cell adhesion may be interpreted as the involvement of PGs of the cell
      surface in cell adhesion, possibly affecting the various processes
      (proliferation, angiogenesis and metastasis) of prostate tumor progression.
      Although similar interferences of nonnatural GAGs with cell-adhesion-associated
      proliferation of anchorage-dependent cells remain to be established under in vivo
      conditions, this type of compounds deserves further attention as a tool with
      which to study the role of cell adhesion in the progression of prostate cancer
      and as a potential candidate for the development of a stromal-epithelial targeted
      therapy.

PMID- 9144894
TI  - Stromal inhibition of epithelial cell growth in the prostate; overview of an
      experimental study.
AB  - The paracrine influence of prostatic stroma on the proliferation of prostatic
      epithelial cells was investigated. Using a double-layer soft agar assay it was
      demonstrated that stromal cells from the human prostate inhibit the anchorage
      independent growth of the prostatic tumor epithelial cell lines PC-3 and LNCaP.
      Anchorage-dependent growth was inhibited too as was shown in the semi-automated
      colorimetric MTT test performed on multiwell plates. Antiproliferative activity
      was mediated by a diffusible factor in the stromal cell conditioned medium and
      was found to be produced specifically by prostatic stromal cells. Although the
      putative inhibiting factor shared some properties with transforming growth factor
      beta (TGF-beta) evidence is presented that the factor is different from this well
      known inhibitor of epithelial cell growth. Absence of TGF-beta activity was shown
      by the lack of inhibitory response of the TGF-beta-sensitive mink lung cell line
      CCL-64 to prostate stromal cell conditioned medium and to concentrated partially
      purified preparations of the inhibitor. Furthermore, neutralizing antibodies
      against TGF-beta 1 or TGF-beta 2 did not cause a decline in the level of PC-3
      growth inhibition caused by partially purified inhibitor. It is concluded that
      the prostate stroma-derived factor may be a novel growth inhibitor different from
      any of the currently described inhibiting factors.

PMID- 9144895
TI  - Conservative non-instrumental treatment of benign prostatic hyperplasia.
AB  - This paper critically reviews the clinical effects in benign prostatic
      hyperplasia (BPH) patients that can be achieved with the presently available
      medical treatment options. The classes of drugs that are reviewed include: 5
      alpha-reductase inhibitors, alpha-blockers, cholesterol-lowering agents and
      phytotherapeutic drugs. Only double-blind placebo-controlled studies with a
      duration of at least 3 months that have reported symptomatic changes and changes
      in flow rate in a quantitative fashion have been included. Studies that
      exclusively included selected groups of patients such as hypertensives or non
      hypertensives have been excluded. The results of the clinical trials that are
      reviewed in this paper often show improvements in symptom score and maximum flow
      rate in the patients taking the active drug. These improvements are often
      statistically significantly better than the improvements seen in the placebo
      groups. However, taking into account that the symptomatic and the flow rate
      improvements achieved are below the level of perception in most of these trials,
      there seems to be no convincing evidence that medical treatment of BPH with the
      presently available drugs is also clinically more effective than placebo.

PMID- 9144896
TI  - Natural history of superficial bladder tumors: 10- to 20-year follow-up of
      treated patients.
AB  - Superficial bladder tumors (Ta, Tl, Tis) account for 80% of primary bladder
      cancers. Transurethral resection and intravesical therapy are successful in
      controlling the majority of these tumors for up to 5 years. However, patients
      with multiple or recurrent Ta, Tl and Tis bladder cancer have a lifelong risk of
      developing stage progression and upper tract tumors. One-half are at risk of
      having cystectomy eventually and one-third are at risk over a 15-20 year period
      of dying of bladder cancer.

PMID- 9144897
TI  - Current concepts in the role of intravesical instillations in the therapy and
      prophylaxis of superficial transitional-cell cancer of the bladder. The
      Finnbladder Research Group.
AB  - A survey on superficial, local urinary bladder cancer, its prognostic factors,
      and instillation treatments is presented on the basis of experience with
      approximately 1,000 patients over a period of 20 years, experimental
      investigations, and the literature. Personal opinions and practical
      recommendations are presented in 11 conclusive theses.

PMID- 9144899
TI  - The use of the BTA Test in the detection of persistent or recurrent transitional
      cell cancer of the bladder.
AB  - The BTA Test1 is an adjunctive test for the diagnosis and management of bladder
      cancer. For estimation of its potential in the management of patients with
      transitional-cell cancer (TCC) a review of published results was undertaken.
      Three prospective studies were analyzed, in which a total of 699 patients with a
      history of TCC were enrolled. The BTA Test was performed on voided urine and
      compared with either voided-urine or bladder-wash cytologic analysis in a blinded
      fashion. In all three studies the sensitivity of the BTA Test was more than
      double that of cytology, irrespective of whether the cytologic analysis was
      performed on voided or bladder-wash samples. The third study also included an
      additional 225 patients undergoing evaluation for hematuria, and TCC was found in
      67 cases. The BTA Test detected 70% of these tumors, whereas cytology detected
      only 25%. The BTA Test is a simple, rapid test that can diagnose a substantial
      percentage of patients having new or recurrent bladder TCC. Its complete role in
      the management of such patients remains to be defined.

PMID- 9144900
TI  - The role of nuclear matrix protein 22 in the detection of persistent or recurrent
      transitional-cell cancer of the bladder.
AB  - Successful management of transitional-cell carcinoma of the urinary bladder is
      greatly dependent upon regular surveillance and early detection of persistent or
      recurrent carcinoma. The development of a highly sensitive urinary test for the
      detection of transitional-cell carcinoma of the bladder could have a dramatic
      impact on our ability to diagnose and monitor bladder cancer patients as well as
      influence the treatment outcome. The urinary level of the nuclear matrix protein,
      NMP22, has been found to be elevated in patients with urothelial malignancy. This
      has prompted the development of an immunoassay to quantitate urinary NMP22 and
      use it as a cancer-specific marker. We provide a summary of the studies completed
      with the immunoassay for urinary NMP22 as an indicator for the presence of
      transitional-cell carcinoma and compare the results with those obtained using
      other screening modalities.

PMID- 9144898
TI  - Biologic response modifiers in the management of superficial bladder cancer.
AB  - For the treatment of existing transitional-cell carcinoma or for prophylaxis of
      recurrent disease, intravesical therapy should be chosen according to stage.
      Papillary disease (stages Ta, Tl) may be treated effectively either with an
      alkylating agent or with bacillus Calmette-Guerin (BCG). BCG is the agent of
      choice for the treatment of Hat carcinoma in situ (Tis), with the recommended
      treatment course comprising 12 weekly and 12 monthly instillations. Intravesical
      interferon and many of the other biologic response modifiers mentioned herein may
      be effective for patients with Ta disease who have failed BCG therapy.

PMID- 9144902
TI  - Applications of telomerase in urologic oncology.
AB  - Vertebrates have special structures at the ends of their chromosomes, known as
      telomeres, which are composed of 5- to 15-kb pairs of a guanine-rich hexameric
      repeat (TTAGGG)n. In normal somatic cells there is a progressive degradation of
      telomeres with aging. The cell can afford to lose only a finite number of these
      telomeres before significant sequences of the parent DNA are lost, resulting in
      chromosomal instability and cell death. However, germ-cell telomeres are
      maintained despite multiple rounds of replication. This suggests that they
      produce an enzyme that maintains their telomere length. This enzyme, a
      ribonucleoprotein, is called telomerase. In this review, we discuss the presence
      of telomerase activity in various human cancers and, in particular, in urologic
      tumors. We describe the potential clinical utility of detection of the presence
      of telomerase activity in cells from voided urine samples of patients with
      bladder cancer.

PMID- 9144901
TI  - Molecular and immunopathology studies of oncogenes and tumor-suppressor genes in
      bladder cancer.
AB  - Target genes implicated in cellular transformation and tumor progression have
      been divided into two categories: proto-oncogenes (that when activated become
      dominant events characterized by gain of function) and tumor-suppressor genes
      (recessive events characterized by the loss of function). Alterations in proto
      oncogenes and tumor-suppressor genes seem equally prevalent among human cancers.
      Multiple mutations appear to be required to conform the malignant phenotype. It
      is therefore conceivable that cancer be viewed fundamentally as a genetic disease
      entailing inherited (also called germ-line) and/or acquired (also termed somatic)
      mutations of genes in these two categories. Molecular studies of bladder
      neoplasms have identified a series of nonrandom genetic alterations affecting a
      particular set of oncogenes and tumor-suppressor genes. Because the modality of
      therapy for patients with bladder neoplasms primarily depends on morphological
      evaluation and clinical staging, the diagnosis carries significant consequences.
      However, it is well known that morphologically similar tumors presenting in any
      assigned stage may behave in radically different fashions, which seriously
      hampers the physician's ability accurately to predict clinical behavior in a
      given case. Recent studies have shown that inactivation of certain tumor
      suppressor genes, such as RB and TP53, occur in bladder tumors that have a more
      aggressive clinical outcome and poor prognosis. In the present paper we review
      the molecular abnormalities associated with these dominant and recessive genes in
      bladder cancer and discuss the potential clinical use of their detection. The
      implementation of objective predictive assays to identify these alterations in
      clinical material will enhance our ability to assess tumor biological activities
      and to design effective treatment regimens. The need now is to translate this
      newly developed scientific knowledge into diagnostic and therapeutic strategies,
      which in turn will enhance the quality of life and prolong the survival of
      patients with bladder cancer.

PMID- 9144904
TI  - Update of urethra-sparing approaches in cystectomy in women.
AB  - The emerging experience in urethra-sparing cystectomy in women undergoing
      subsequent orthotopic lower-urinary-tract reconstruction with regard to the
      anatomy of the remnant urethra, patient selection, refinements of the surgical
      technique, the patients' outcome with respect to the underlying disease, the risk
      for tumor recurrence, and postoperative urodynamics are the main focus of this
      report. In the present study, 30 carefully selected female patients underwent
      orthotopic reconstruction of the lower urinary tract. Surgical variations
      emerging from the first learning curve, including nerve-sparing anterior
      exenteration, vaginal reconstruction, omental support of the neobladder floor,
      and ureterointestinal anastomosis, were applied in 21 patients with lower-urinary
      tract reconstruction. Of 24 patients followed for more than 6 months, 21 (87.5%)
      are continent at daytime, 19 (79%) have nocturnal continence, and only 1 (4%)
      requires self-catheterization; 3 patients with urinary retention were
      successfully treated for obstructed ileal valves. After a follow-up period of 2
      41 (mean 15.4) months one patient each developed local recurrence (uterine
      adenosarcoma) after 13 months and distant metastasis transitional-cell cancer of
      the bladder after 3 months; all other patients are currently free of disease.
      Urethra-sparing surgery has established itself in selected women with bladder
      cancer. Refinements in the technique of radical cystectomy and orthotopic
      creation of a neobladder to the urethra may improve the continence, spontaneous
      micturition, and surgical oncological outcome of these patients.

PMID- 9144903
TI  - New approaches in the use of radiation therapy in the treatment of infiltrative
      transitional-cell cancer of the bladder.
AB  - Organ preservation using primary radical radiation therapy (RT) is a viable
      treatment option for many patients with invasive bladder cancer, and there is no
      evidence that survival is compromised by this approach. However, the survival and
      local control rates in patients with bladder cancer currently treated with
      radical RT are not optimal. Combined modality therapy, altered radiation
      fractionation approaches, and exciting new approaches such as the application of
      gene therapy and the use of hypoxic cell sensitisers, among others, may well
      improve the results of treatment in the future. Ongoing clinical research,
      including prospective randomised trials, will be required to evaluate these new
      approaches to therapy.

PMID- 9144905
TI  - New approaches in the treatment of metastatic transitional-cell cancer of the
      bladder.
AB  - In recent years, chemotherapy of metastatic transitional-cell carcinoma of the
      bladder has advanced from the use of individual therapeutic agents, which has
      effected only rare responses, to the development of multi-agent regimens, which
      have greatly improved both partial and complete response rates, resulting in
      improved local care, palliation, and; perhaps, survival. However, because of the
      limited duration of response, frequent recurrences, and the significant
      proportion of patients with refractory disease, there have been only modest
      overall gains in long-term disease-free survival. These shortcomings have
      prompted investigation of alternative approaches to current combination
      chemotherapy regimens, including the use of hematopoietic growth factors and
      novel single-agent, multi-agent, and gene therapy protocols.

PMID- 9144906
TI  - Efficacy and safety of two doses of tolterodine versus placebo in patients with
      detrusor overactivity and symptoms of frequency, urge incontinence, and urgency:
      urodynamic evaluation. The International Study Group.
AB  - Tolterodine is a new competitive muscarinic receptor antagonist developed for the
      treatment of the unstable bladder. A total of 242 patients were enrolled in a
      multicenter, multinational, randomized, double-blind, placebo-controlled study
      conducted over a period of 4 weeks in patients with detrusor overactivity and
      symptoms of frequency, urgency, and urge incontinence. The objective of the study
      was to compare the efficacy and safety of tolterodine given at 1 or 2 mg b.i.d.
      versus placebo. At week 4 a statistically significant increase in the volume at
      first contraction (p = 0.030) and maximal cystometric capacity (p = 0.034) was
      only in the tolterodine 2 mg b.i.d. group. Tolterodine was safe and generally
      well tolerated. The incidence of dry mouth, as the most commonly reported adverse
      event, was only 9% and of mild to moderate intensity.

PMID- 9144907
TI  - Relationships among strains classified with the ruminant Pasteurella haemolytica
      complex using quantitative evaluation of phenotypic data.
AB  - The phenotypic relationships among 246 trehalose-negative strains classified
      under the [Pasteurella] haemolytica-complex in ruminants were investigated by
      clustering and multidimensional ordinations based upon 79 phenotypic characters.
      A quantitative evaluation of phenotypic data using a 5-level scoring system is
      presented permitting a comprehensive utilization of the recorded phenotypic
      variation among the strains in the analyses. Clustering and ordination analyses
      display complementary aspects of data which has been clearly demonstrated in this
      investigation. The main clusters revealed by the numerical techniques could be
      related to distinctive phenotypic differences and showed an extensive correlation
      with the recognized biogroups. This classification was based only upon 4
      characters (fermentation of L-arabinose, D-sorbitol, glucosides and ornithine
      decarboxylase). In contrast, there was no obvious interpretation of the clusters
      formed by using binary scores. Phenotypic subgroups within the recognized
      biogroups have been described as well as a new, related group of bacteria,
      tentatively named Bisgaard taxon 36. Quantitative interpretation of phenotypic
      data seems to represent a promising method for finding relations among affiliated
      strains of bacteria and to assist in forming hypotheses for subsequent genotypic
      investigations.

PMID- 9144908
TI  - Rapid and sensitive detection of Campylobacter spp. from chicken using the
      polymerase chain reaction.
AB  - The polymerase chain reaction (PCR) using a target region in the flaA gene of C.
      coli VC167 flagellin was used to detect Campylobacter spp. in chicken without an
      enrichment culture. DNA extracted from 79 cloacal swabs from broiler chickens
      gave an amplification signal in the 450-bp region upon PCR. DNA extracted from 9
      enteric and 6 non-enteric organisms included in the assay as negative controls
      failed to hybridize with the probe. Direct plating of all cloacal specimens on
      Campylobacter blood agar plates did not yield any growth. The PCR assay was
      sensitive enough to detect between 35-120 bacteria per PCR and thus provide a
      basis for detecting Campylobacter spp. in poultry.

PMID- 9144909
TI  - Arsenate resistance as a possible marker in the differentiation of environmental
      and clinical isolates of Vibrio parahaemolyticus.
AB  - Strains of Vibrio parahaemolyticus were isolated from clinical, marine and
      freshwater fish of Calcutta, West Bengal, India. Drug and metal resistance
      characteristics were compared for differentiation of clinical and environmental
      strains. Eighteen out of the twenty environmental isolates were resistant to
      arsenate, unlike the clinical isolates which were all susceptible. All the thirty
      five isolates of V. parahaemolyticus were resistant to ampicillin and
      streptomycin.

PMID- 9144910
TI  - Listeria monocytogenes infection in mice treated with pentoxifylline.
AB  - The course of L. monocytogenes infection was followed in mice treated with
      pentoxifylline (POF), a known inhibitor of endogenous tumor necrosis factor (TNF)
      formation. Administration of POF caused a delay in L. monocytogenes elimination
      which was probably related to a reduction the listericidal activity of
      macrophages and to an attenuation of delayed type hypersensitivity (DTH) to
      Listeria antigens. In spite of this, some POF-treated mice were protected from
      lethal effects of virulent L. monocytogenes bacteria.

PMID- 9144912
TI  - Surface vesicles: a possible function in commensal relations of Bacteroides
      fragilis.
AB  - Surface vesicles (SV) defined by electron microscopy as outer membrane (OM)
      extrusions were detected in Bacteroides fragilis strains from distinct sources. A
      partial identity between SV and OM electrophoretic protein profiles, in addition
      to the microscopic analysis, may suggest the designation of OMSV. Sialidase
      activity, a virulence determinant, was associated with these sub-cellular
      structures in all the strains, but in an inverse relation to the vesicle quantity
      per cell. A commensal strain, previously defined as avirulent in an animal model,
      presented the lowest vesicle-associated sialidase activity and the greatest SV
      expression as opposed to what happened with clinical and environmental strains.
      These results seem to suggest that these surface components have a function in
      commensal stages of B. fragilis.

PMID- 9144911
TI  - Adherence of Borrelia burgdorferi to granulocytes of different animal species.
AB  - Adherence of 4 Borrelia (B.) burgdorferi strains (z7/22, z7/27, z7/41, PBi) to
      polymorphonuclear granulocytes from different domestic animals (horses, cattle,
      sheep, dogs) was investigated. All 4 strains adhered to the granulocytes. Binding
      assays indicated that the adherence occurred between structures on the surface of
      the borreliae ("binding-sites") and on the membranes of the granulocytes
      ("receptors"). The "receptors" consisted of 4 fractions (A, B, C, and D) with
      components differing in molecular weight (MW) and binding activity for proteins
      on the surface of B. burgdorferi. Fraction A (MW 80000) had the highest binding
      activity for B. burgdorferi.

PMID- 9144913
TI  - In vitro permeation of human chorioamniotic membranes by Campylobacter jejuni.
AB  - In vitro penetration of human chorioamniotic membranes by Campylobacter jejuni
      was investigated by an organ culture model. Membrane permeation was detected by
      an immunoperoxidase technique and viable bacterial counts of membrane
      homogenates. Human clinical isolates of C. jejuni inoculated on the maternal side
      of the membranes penetrated to the fetal side suggesting that chorioamniotic
      membranes constituted a weak barrier against Campylobacter infection. Chicken
      fecal isolates did not penetrate chorioamniotic membranes. In vitro culture
      conditions did not affect the viability of membranes. Human placental extracts
      and amniotic fluids enhanced the in vitro growth of C. jejuni. These results
      suggest that certain strains of C. jejuni may penetrate intact fetal membranes
      and this event may play a role in the pathogenesis of infection.

PMID- 9144914
TI  - Comparison of seven commercial tests for the detection of parvovirus B19-specific
      IgM.
AB  - Several enzyme immunoassays (EIA) for the detection of parvovirus B19 IgM (anti
      B19 IgM) are now commercially available. In this study, seven commercial EIAs
      (Biotrin, DAKO, Viramed, Viratech, R-Biopharm, Mast) were compared with an in
      house EIA (MvP-EIA) using native viral B19 particles and the reference IgM
      radioimmunoassay (MACRIA). A total of 88 sera were tested. Results agreed in
      39/88 (44.3%) sera, whereas 47/88 (53.4%) were discrepant and 2/88 (2.3%) gave an
      equivocal result. Assay sensitivity ranged from 70.3 to 100% and specificity,
      from 75.9 to 100%. The best results were obtained with two EIAs (Biotrin, DAKO)
      using baculovirus-expressed B19 proteins as antigen. This study has shown that
      baculovirus-expressed B19 antibody tests are suitable tools for detecting anti
      B19 IgM.

PMID- 9144915
TI  - Pathological and epidemiological aspects of skin lesions in histoplasmosis.
      Observations in an AIDS patient and badgers outside endemic areas of
      histoplasmosis.
AB  - As a consequence of HIV infection, histoplasmosis is increasingly occurring as an
      opportunistic infection with a systemic course outside histoplasmosis-endemic
      areas, e.g. in Europe. Accordingly, questions concerning the epidemiology of this
      mycosis arise. Two incidents involving histoplasmosis in man and badgers with
      prevailing involvement of the skin encouraged us to review the pathogenesis and
      epidemiology of this mycosis in Germany, where so far Histoplasma capsulatum has
      not been endemic. With a view to prevention, attention is drawn to the avoidance
      of microfoci of H. capsulatum in the newly introduced concept of biowaste and its
      composting plants in countries with modern waste management.

PMID- 9144916
TI  - Isolation of an Acanthamoeba strain with intracellular Burkholderia pickettii
      infection.
AB  - Burkholderia pickettii is a facultative pathogen that has been isolated from
      patient sources and environmental sources including respiratory therapy
      solutions, deionized water and aqueous disinfectants. The organism has been
      associated with septicemia and respiratory tract infections. In our
      investigation, Burkholderia pickettii (biovar 2) was for the first time isolated
      from Acanthamoeba sp. (group II), a free living amoeba species recovered from the
      wet area of a physiotherapy unit. Pathogenic strains of acanthamoebae may cause
      amoebic-encephalitis (AE) and keratitis. Light and electron microscopic
      examinations showed that in a first step, the bacterial were phagocytized by the
      amoebae. In contrast to Enterobacter cloacae and Escherichia coli that were used
      as food organisms and digested within food vacuoles, Burkholderia pickettii
      caused the amoebae to develop large vacuoles filled with completely intact and
      motile bacteria. 3-5 days after infection, Pseudomonas pickettii had multiplied
      within the enlarging parasitophorous vacuoles. Ultrastructural changes in the
      host cells occurred and the amoebae finally underwent rupture or lysis. In
      cocultivation assays we could not only reinfect the original host amoeba but
      Acanthamoeba strains from other habitats could successfully be infected with
      Burkholderia pickettii as well.

PMID- 9144917
TI  - Apodemus sp. rodents, reservoir hosts for Borrelia afzelii in an endemic area in
      Switzerland.
AB  - Borrelia burgdorferi is maintained in nature in transmission cycles alternatively
      involving ticks and reservoir hosts. Small rodents like Apodemus mice and
      Clethrionomys voles are the primary reservoir of Lyme disease in Europe. In this
      study, we analyzed by SDS-PAGE and Western blot 20 borrelial isolates from
      xenodiagnostic ticks fed on four Apodemus sp. mice captured in the Staatswald
      forest (Switzerland). All isolates but one showed a homogeneous protein pattern
      expressing an outer surface protein, (Osp) A of 32 kDa and an OspB of 35 kDa and
      reacted with monoclonal antibody (mAb) I 17.3 specific for B. afzelii. One
      isolate expressed an OspA of 32.5 kDa and an OspB of 35 kDa and did not react
      with species-specific mAbs I 17.3, D6 and H3TS, but was shown to belong to B.
      afzelii by Southern blot analysis. The possibility exists that non-cultivatable
      borreliae are present in xenodiagnostic ticks. However, our results clearly show
      that Apodemus sp. are reservoir hosts for B. afzelii, since this genospecies is
      transmitted from Apodemus sp. to feeding larval ticks.

PMID- 9144918
TI  - Distribution of bacteria on hands and the effectiveness of brief and thorough
      decontamination procedures using non-medicated soap.
AB  - Our perception of the role of hand washing in the clinical situation is based on
      experimental studies in which test-bacteria are usually inoculated onto the skin
      surface and removed using hand washing preparations containing antiseptics. In
      this study, we have investigated the distribution of bacteria on the hands of
      volunteers and the effectiveness of long (3 minute) and brief (10 second) washes
      in removing both naturally-occurring and artificially-inoculated bacteria
      (Micrococcus sp.), using only soap and water. There was a tenfold reduction in
      median counts of artificially inoculated bacteria following both long and brief
      washes. However, less than 50% of naturally-occurring bacteria were removed and,
      for hands previously disinfected by immersion in 70% ethanol, the washing
      procedure increased bacterial counts. In both unwashed hands, and hands washed
      following a strict protocol, the mean variation in counts of naturally-occurring
      bacteria at different sites (wrists, dorsal surface, palmar surface, fingertips
      and interdigital spaces) was only two-fold. The efficiency of recovery of
      naturally-occurring organisms was estimated by repeated swabbing, to be more than
      60%. The data question the value of typical hand wash procedures recommended by
      many authorities for use in clinical situations and of the perfunctory hand
      washes frequently adopted by nursing staff in busy wards. Experimental evidence
      is required to justify procedures and to identify the precise circumstances in
      which they are of value.

PMID- 9144919
TI  - Junction genetics.

PMID- 9144920
TI  - Localizing the adhesive and signaling functions of plakoglobin.
AB  - Plakoglobin (PKG) is a major component of cell-cell adhesive junctions. It is
      also closely related to the Drosophila segment polarity gene product armadillo
      and can induce a WNT-like neural axis duplication (NAD) phenotype in Xenopus
      [Kamovsky and Klymkowsky, 1995.] To define the regions of PKG involved in cell
      adhesion and inductive signaling, we examined the behavior of mutated forms of
      PKG in Xenopus. Deletion of amino acids 22 through 39 (in the Xenopus PKG
      sequence increased the apparent stability of the polypeptide within the embryo
      and increased its ability to induce a WNT-like, NAD phenotype when expressed in
      the vegetal hemisphere. The N-terminal "head" and first 6 "ARM" repeats of PKG,
      or the C-terminal "tail" and the last 3 "ARM" repeats, could be removed without
      destroying the remaining polypeptide's ability to induce a NAD phenotype. The
      nuclear localization of mutant PKGs, however, was not strictly correlated with
      the ability to induce a NAD phenotype, i.e., some inactive polypeptides still
      accumulate in nuclei. Removal of PKG's head and first ARM repeat, which includes
      its alpha-catenin binding site, resulted in a polypeptide that, when expressed in
      the embryo, generated alpha dramatic cell adhesion defect. Removal of the next
      three ARM repeats abolished this adhesion defect, suggesting that the polypeptide
      no longer competes effectively with endogenous catenins for binding to cadherins.
      Expression of a form of PKG truncated after the 5th ARM repeat produced a milder
      cell adhesion defect, whereas expression of a polypeptide truncated after the 8th
      ARM repeat had little apparent effect on cellular adhesion. Based on these
      observations, we conclude that functions related to stability and cellular
      adhesion reside in the N-terminal region of the polypeptide, whereas the ability
      to induce a NAD phenotype lies within repeats 6-10 of the central region. The
      function(s) of the C-terminal domain of PKG remain uncertain at this time.

PMID- 9144921
TI  - Expanded functions in the apical cell domain to regulate the growth rate of
      imaginal discs.
AB  - The Drosophila expanded (ex) gene encodes a product (Ex) that shares homology
      with the Protein 4.1 family of proteins, many of which are enriched at specific
      lateral cell junctions and the apical cellular domain. Ex colocalizes with actin
      in the apical domain of imaginal disc epithelial cells, where it partially
      overlaps the distribution of phosphotyrosine (PY)-containing proteins. This
      suggests that Ex is present in or associated with adherens junctions. Genetic
      studies show that Ex is necessary for proper regulation of final cell number in
      adult wings and for the formation of eyes, distal leg, and distal antennal
      segments. We have generated mitotic clones that lack Ex using the twin spot
      technique, and demonstrated that the primary function of Ex is to regulate cell
      proliferation. Overexpressing Ex protein results in a decrease in final cell
      number in wings, suggesting a direct relationship between Ex function and
      proliferation rate.

PMID- 9144922
TI  - Localization of proteins to the apico-lateral junctions of Drosophila epithelia.
AB  - We have examined the distribution of proteins in the apico-lateral cell junctions
      in Drosophila imaginal discs. The subcellular distribution of these proteins in
      normal and mutant proliferating cells was analyzed with marker antibodies and
      confocal microscopy. Antibodies to phosphotyrosine (PY), Armadillo (Arm) and
      Drosophila E-cadherin (DE-cad) as well as FITC phalloidin marking filamentous
      actin, labeled the site of the adherens junction, whereas antibodies to Discs
      large (DIg), Fasciclin III (FasIII) and Coracle (Cor) labeled the more basal
      septate junction. The junctional proteins labeled by these antibodies underwent
      specific changes in distribution during the cell cycle. We have previously shown
      that a loss-of-function dlg mutation, which causes neoplastic imaginal disc
      overgrowth, leads to loss of the septate junctions and the formation of what
      appear to be ectopic adherens junctions [Woods et al., 1996]. We therefore
      extended this study to examine the effects of mutations in other genes that also
      cause imaginal disc overgrowth. Based on staining with PY and DIg antibodies, the
      apico-lateral junctional complexes appeared normal in tissue from the
      hyperplastic overgrowth mutants fat, dco, gd and wts. However, imaginal disc
      tissue from the neoplastic overgrowth mutants dlg and lgl showed abnormal
      distribution of the junctional markers including a complete loss of apico-basal
      polarity in loss-of-function dlg mutations. These results support the idea that
      some of the proteins of apico-lateral junctions are required both for apico-basal
      cell polarity and for the signalling mechanisms controlling cell proliferation,
      whereas others are required more specifically in cell-cell signalling.

PMID- 9144923
TI  - Cx43 gap junction gene expression and gap junctional communication in mouse
      neural crest cells.
AB  - Although gap junctions are not known to be important in mediating cell-cell
      interactions amongst migratory cells, our studies showed that the connexin 43
      (Cx43) gap junction gene is widely expressed in mouse neural crest cell lineages.
      Using in situ hybridization analysis, Cx43 expression was detected in presumptive
      neural crest cells emerging from the neural folds of the early postimplantation
      embryo. Neural crest expression of the Cx43 gap junction gene was also indicated
      by the analysis of transgenic mice containing a lacZ reporter construct driven by
      the Cx43 promoter. In neural tube explant cultures of these transgenic mice, lacZ
      expression was observed in the emerging neural crest outgrowths. Whole mount X
      gal staining of these transgenic embryos at various stages of development showed
      lacZ expression in neural crest cells distributed along the entire craniocaudal
      axis, with expression found in both cranial and trunk neural crest cells
      contributing to a wide range of embryonic tissues. This included presumptive
      cardiac neural crest cells localized in the heart. In light of the widespread
      expression of Cx43 in neural crest cell lineages, dye injection studies, were
      carried out to determine if neural crest cells are functionally coupled via gap
      junctions. Such studies revealed extensive dye coupling among presumptive neural
      crest cells, thus demonstrating that these migratory cells are indeed gap
      junctional communication competent. In total, these observations suggest that gap
      junctions may play a role in mouse neural crest development. This possibility is
      particularly intriguing given the recent finding that the Cx43 knockout mice die
      of defects associated with the outflow tract [Reaume et al., 1995], a region of
      the heart in which neural crest cells are required for normal development.

PMID- 9144924
TI  - Blocking gap junctional intercellular communication in myoblasts inhibits
      myogenin and MRF4 expression.
AB  - Cells rely heavily on cues from their extracellular environment and other cells
      to coordinate normal physiological processes, and the exchange of molecules via
      gap junctions has been suggested as on important avenue for cell-cell
      communication. Gap junctions are found in virtually all mammalian tissues with
      the notable exception of adult skeletal muscle. However, since functional gap
      junctions have been detected during the early stages of muscle development, gap
      junctional intercellular communication (GJIC) may play on important role in
      myogenesis. In this study, GJIC in normal 16 myoblasts was inhibited using the
      known blockers l-octanol and beta-glycyrrhetinic acid (beta-GA). Under
      differentiation promoting conditions, 16 cells fused to form multinucleated
      myotubes, but when treated with either octanol or beta-GA, no fusion was
      observed. The expression of two muscle regulatory factors (MRFs), myogenin and
      MRF4, was examined in both the blocked and control cells. As expected, the
      activation of both the myogenin and MRF4 genes coincided with the onset of
      differentiation in the control 16 cells. Neither of these genes were turned on in
      the blocked cells, even when grown under low serum conditions. This inhibition of
      differentiation by octanol and beta-GA was reversible, since the activation of
      both MRF genes as well as myoblast fusion were observed when the blocking medium
      was replaced with normal differentiating medium. These results suggest that
      intercellular communication via gap junctions plays an important role in skeletal
      muscle development and perhaps in the cell signaling events that trigger the
      activation of muscle-specific MRF genes.

PMID- 9144925
TI  - Expression pattern of an axolotl floor plate-specific fork head gene reflects
      early developmental differences between frogs and salamanders.
AB  - Gastrulation is one of the most important stages of animal development and, as
      such, tends to be remarkably conserved. Therefore it is interesting to see that
      the two amphibian species, Xenopus laevis (frog) and Ambystoma mexicanum
      (axolotl), are different in the arrangement of cell types just before and during
      gastrulation. In Xenopus, the cells that will form dorsal mesoderm are located
      deep in the dorsal marginal zone, while in the axolotl, these are on the surface
      of the embryo. In this study we investigated whether homologous genes known to be
      involved in the formation of dorsal structures show a different pattern of
      expression in these two species. For this purpose, we isolated a fork head gene
      (AxFKH 1) from the axolotl, which is likely to be the homologue of the Xenopus
      fork head gene, XFKH 1 (Pintallavis, XFD-1). We find that AxFKH 1 and XFH 1 have
      a similar pattern of expression, but there are some important differences. In
      early gastrulae, transcripts are detected in the organizer region of both
      species. In late gastrulae, the transcripts in Xenopus are located in both the
      superficial and deep layers, but they are only found in the superficial layer of
      axolotl embryos. During neurulation, XFKH 1 is expressed in notochord and neural
      floor plate, whereas AxFKH 1 is expressed in the neural floor plate only. We
      propose that the differences in expression pattern of these two genes are due to
      a difference in formation of dorsal structures between these two species.
      Furthermore, the expression pattern of these two genes early in gastrulation is
      consistent with the idea that at least some of the neural floor plate cells are
      already determined at this time.

PMID- 9144926
TI  - Role for the Rana catesbeiana homologue of C/EBP alpha in the reprogramming of
      gene expression in the liver of metamorphosing tadpoles.
AB  - During the spontaneous or thyroid hormone (TH)-induced metamorphosis of Rana
      catesbeiana, developmental changes occur in its liver that are necessary for the
      transition of this organism from an ammonotelic larva to a ureotelic adult. These
      changes include the coordinated expression of genes encoding the urea cycle
      enzymes carbamyl phosphate synthetase (CPS-I) and arnithine transcarbamylase
      (OTC). Although the expression of these genes is dependent on TH, the
      mechanisms(s) by which TH initiates this tissue-specific response is thought to
      be indirect and to involve early TH-induced upregulation of a gene(s), which, in
      turn, upregulates the coordinated expression of these urea-cycle enzyme genes.
      Herein, we demonstrate that mRNAs encoding the Rana homologue of the mammalian
      transcription factor C/EBP alpha (designated RcC/EBP-1) accumulate early in
      response to TH and that the product of these mRNAs can bind to and transactivate
      the promoters of both the Rana CPS-1 and OTC genes. These results support the
      contention that the reprogramming of gene expression in the liver of
      metamorphosing tadpoles involves a TH-induced cascade of gene activity in which
      RcC/EBP-1 and, perhaps, other transcription factors coordinate the expression of
      genes, such as those encoding CPS-I and OTC, whose products are characteristic of
      the adult liver phenotype.

PMID- 9144927
TI  - Nurse cell polytene chromosomes of Drosophila melanogaster otu mutants:
      morphological changes accompanying interallelic complementation and position
      effect variegation.
AB  - Combinations of certain mutant alleles of the ovarian tumor gene permit the
      production of viable eggs. Two alleles that behave in this way are otu7 and
      otu11. Females homozygous for either allele are sterile, and their ovarian nurse
      cells (NC) contain giant polytene chromosomes of various morphologies. Fertile
      flies (otu+/otu+, otu+/otu7, otu+/otu11) have endopolyploid nurse cells with
      typical dispersed chromosomes. Fertile hybrids (otu7/otu11) produce large numbers
      of polytene chromosomes comparable to, and often larger than, classic salivary
      gland (SG) chromosomes. Therefore, these otu hybrids provide a unique system for
      studying, at the chromosomal level, the activation and expression of genes
      functioning during oogenesis. The otu gene encodes a long and a short isoform.
      The normal long isoform appears to be responsible for the dispersion of
      chromosomes during the endomitolic DNA replications occurring in ovarian NCs. The
      genetic inactivation of euchromatic genes placed next to pericentric
      heterochromatin by a chromosomal rearrangement is accompanied by the compaction
      of corresponding chromosome regions. A comparative study of the manifestation of
      position-effect variegation for the polytene chromosomes of SG cells and NCs was
      made using the Dp(1;1)pn 2b and Dp(1;f)1337 rearrangements. The percentage
      frequencies of block formation in the SG and NC nuclei for Dp(1;1)pn 2b
      rearrangement were 92.6% vs. 15.8%, respectively; for Dp(1;f) 1337, these values
      were 56.8% vs. 9.7%. Therefore heterochromatin belonging to germ line chromosomes
      is in a configuration that is far less likely to inactivate inserted segments of
      euchromatin than is heterochromatin from somatic chromosomes.

PMID- 9144928
TI  - Reversed-phase high-performance liquid chromatographic separation of LY309887
      (thienyl-5,10-dideazatetrahydrofolate) stereoisomers using beta-cyclodextrin as a
      mobile phase additive.
AB  - The separation of the four stereoisomers of LY309887 (thienyl-5,10
      dideazatetrahydrofolate) is studied here using commercially available high
      performance liquid chromatography column technology. The selectivity needed to
      resolve the four stereoisomers is provided by an achiral reversed-phase column
      used with beta-cyclodextrin as a mobile phase additive. The separation is
      dependent on triethylamine and beta-cyclodextrin concentration in the buffer
      portion of the eluent, eluent strength, and buffer pH.

PMID- 9144929
TI  - A new variant of "subjective" delusional misidentification associated with
      aggression.
AB  - Delusional misidentification syndromes are psychotic conditions in which the
      affected individual experiences delusions of radical change concerning the
      identity of others and/or of the self. These syndromes may lead to aggression,
      including serious violence toward others. In this article, we describe and
      analyze in detail an aggressive individual who suffered from a delusion that
      physical and psychological replicas of himself existed. We specifically analyze
      the link between the patient's subjective misidentification delusion and his
      resulting aggression. Both the roles of phenomenology and biology of delusional
      misidentification are evaluated as potential contributors of aggression.

PMID- 9144930
TI  - A validation study of the influence of alcohol on handwriting.
AB  - The purposes of this article are to report experimental findings and to validate
      prior selected studies that examined handwriting comparisons and alcohol
      consumption. Subjects who participated in this experiment were given handwriting
      testing forms which were completed at assigned intervals throughout the testing
      period. The setting for the completion of the experiment was within a controlled
      environment with adult students attending the Breath Tests for Intoxication
      School for the use of blood alcohol concentration (BAC) instruments for law
      enforcement purposes. Handwriting data and pertinent information, BAC level and
      time, were recorded on the testing forms which were completed before, during, and
      after drinking. This study does not attempt to determine handwriting
      characteristics that can be predicted at various blood alcohol levels, but rather
      demonstrate, as noted in prior studies, if handwriting trends develop during or
      after the consumption of alcohol. The results of the handwriting comparisons,
      between and among test subjects, are discussed and applied to prior findings.

PMID- 9144931
TI  - The anthropometry of contemporary commercial cremation.
AB  - This study establishes baseline parameters and examines those variables thought
      to influence cremains weights. Data were collected during the cremation of 100
      individuals. A series of measurements was taken to determine relative skeletal
      robusticity. The weight, stature, sex, and age of each cadaver was recorded prior
      to cremation. The average cremains weight for the fully developed adults (n = 91)
      was 2430 g and ranged from 876 g to 3784 g. Male and female means were separated
      by 1053 g, but there was considerable overlap in the distribution. All cremains
      weights above 2750 g were male and all cremains weights below 1887 g were female.
      Five amputees and one long bone donor produced cremains weights below the means
      for their respective groups, reflecting the relative contribution of the thick
      cortical bone of the limbs to total skeletal weight, and thus to total cremains
      weight. Cremains weight represented approximately 3.5% of total body weight in
      adults, 2.5% of total body weight in children, and approximately 1% of total body
      weight in fetuses. The most accurate predictor of cremains weight was cadaver
      stature (r = .8473; p < .01). Calculated skeletal weight was also highly
      correlated with cremains weight (r = .7986; p < .01). Cadaveric weight was least
      correlated with cremains weight (r = .5470; p < .01). Regression formulae were
      calculated for each of the variables.

PMID- 9144932
TI  - Analysis of gunshot residues on human tissues and clothing by X-ray
      microfluorescence.
AB  - The analysis of gunshot residues on human tissues and clothing in suicide,
      homicide, suspicious death, or attempted murder events, permits the forensic
      scientist to confirm the possibility of an entry wound caused by a gunshot bullet
      from a pistol, revolver, rifle, etc. The residues to be detected are lead (Pb),
      antimony (Sb), barium (Ba) usually from the primer, copper (Cu) and zinc (Zn)
      usually from the metal jacket bullet and iron (Fe) possibly from the barrel of
      the gun used. The presence or absence of these elements and their relative
      concentrations can help in the interpretation of the event.

PMID- 9144933
TI  - Extent of heterogeneity in mitochondrial DNA of European populations.
AB  - Variation in the mitochondrial DNA (mtDNA) control region as detected by sequence
      specific oligonucleotide (SSO) probes is described for 595 individuals from six
      European or European-derived populations. Estimates of diversity for mtDNA types
      exceed 0.91 in all populations, while 50% of the 158 types which were observed
      occur only once. Of 68 shared types, most occur rarely (< 3% of the total
      population); only one type occurs at a frequency greater than 10%, and it is
      present at comparable frequencies in all six populations (18-29%). An analysis of
      molecular variance (AMOVA) incorporating genetic distances between types shows
      that 100% of the variation present in the total sample is attributable to within
      population diversity, while there are essentially no between-population
      differences. Another AMOVA was performed for the first hypervariable region SSO
      sites only, which included this sample plus an additional 537 SSO types from mine
      more European populations that were inferred from published mtDNA control region
      sequence data. Similar results were obtained, with over 99% of the variation
      overall attributable to within-population differences, and less than 1% of the
      variation attributable to between-population differences. The Saami were the most
      different from other populations, which had been observed in an earlier study of
      nucleotide sequence data. Overall, there is no statistically significant
      heterogeneity for European populations (p > 0.001), and these groups are
      virtually indistinguishable with respect to mtDNA SSO types. These results
      demonstrate the utility of mtDNA typing for forensic investigations.

PMID- 9144934
TI  - PCR-based DNA typing of saliva stains recovered from human skin.
AB  - Human bites in cases of homicide, sexual assault, and abuse are often distorted
      due to the elasticity and curvature of the skin. Physical comparison of a bite
      mark to a suspect's teeth is sometimes difficult. Saliva, which is usually
      deposited during biting, can be collected and analyzed to identify the
      perpetrator. Using simulated bite mark situations in two experimental series,
      three samples of 40 microL of whole saliva were deposited on the skin of 27
      cadavers (at 33 sites) and three samples of 100 microL of whole saliva were
      deposited on the skin of 5 cadavers (at 12 sites). Saliva was collected using the
      double swab technique at t = 5 min, t = 24 h, and t = 48 h. DNA was extracted
      using the modified Chelex method and submitted to PCR-based typing at two short
      tandem repeat loci. Results indicate that the concentration of DNA in saliva
      recovered from skin varies as a function of time since deposition. There is a
      significant decrease in concentration in the first 24 h but the concentration
      remains stable from 24 to 48 h. The success of PCR amplification is independent
      of the time since deposition or the concentration of DNA in the saliva sample.
      Contamination from the DNA of the cadaver was not found in any of the cases
      studied.

PMID- 9144935
TI  - Infrared fluorescent detection of PCR amplified gender identifying alleles.
AB  - An automated DNA sequencer utilizing high sensitivity infrared (IR) fluorescence
      technology together with Polymerase Chain Reaction (PCR) methodology was used to
      detect several sex differentiating loci on the X and Y chromosomes from various
      samples often encountered in forensic case work. Amplifications of the X-Y
      homologous amelogenin gene, the alpha-satellite (alphoid) repeat sequences and
      the X and Y chromosome zinc finger protein genes ZFX and ZFY (ZFX/ZFY) were
      performed. DNA extracted from various forensic specimens was amplified using
      either Taq, Tth or ThermoSequenase. Multiplexing using primers for all three loci
      in one reaction tube was achieved using Tth and ThermoSequenase. Two IR labeling
      strategies for detection of PCR products were utilized. In the first strategy,
      one of the PCR primers contained a 19-base extension at its 5' end identical to
      an IR-labeled universal M13 Forward (-29) primer which was included in the
      amplification reactions. During PCR the tailed primer generates sequence
      complementary to the M13 primer which subsequently primes the initial
      amplification products, thereby generating IR-labeled PCR products. In the second
      strategy, dATP labeled with an IR dye (IR-dATP) was included in the amplification
      reaction. During amplification IR-dATP was utilized by the polymerase and
      incorporated into the synthesized DNA, thus resulting in IR-labeled PCR products.
      X and Y specific bands were readily detected using both labeling methodologies.
      Amplified products were electrophoretically resolved using denaturing Long-Ranger
      gels and detected with an automated detection system using IR laser irradiation.
      A separation distance of 15 cm allowed run times of less than 2 h from sample
      loading to detection. Because the gels could be run more than once, at least 120
      samples (2 loads x 60 samples/load) can be typed using a single gel.

PMID- 9144936
TI  - An in vitro experiment for postmortem vascular permeation. The passage of
      morphine and morphine glucuronides across a vascular wall.
AB  - A venous blood sample taken at autopsy cannot be considered to represent the
      antemortem blood concentration of a particular substance. Autolytic processes
      cause disintegration and increasing permeability of the physiological and
      anatomical barriers such as vascular walls and lead to changes in substance
      concentrations. In the present study, the experimental design represents an in
      vitro postmortem simulation of a drug substance crossing a venous wall. The
      postmortem behavior of morphine, morphine-3- and morphine-6-glucuronide was
      investigated. A Chien-Valia-diffusion chamber with a patch of inferior vena cava
      as diffusion barrier was used. For optimal simulation of postmortem events, vein
      sampling was restricted to selected autopsy cases. Parameters for the analysis of
      diffusion across the vascular tissue were dependence on time, temperature, and
      initial substance concentrations. The penetration behavior simulating venous
      efflux and influx of the substances was studied by different orientation of the
      venous wall in the experiments. Rhodamine B was used as a model substance to
      visualize the binding to the tissue and the passage across the venous wall. The
      permeation of morphine, morphine-3- and morphine-6-glucuronide across a vein
      tissue was found to be mainly dependent on the disintegration of the vascular
      wall and on the postmortem time period as well as on concentration gradients.
      From the data of this preliminary in vitro study, it can be concluded that a lag
      time for transvascular diffusion exists postmortem. However, it could be
      demonstrated, that adsorption to and penetration into the vascular tissue may
      alter intraluminal blood concentrations even at an early stage of the postmortem
      time period.

PMID- 9144937
TI  - Digital video image capture in establishing positive identification.
AB  - Positive identification of skeletonized, decomposed, or disfigured victims
      lacking clinical records is a difficult endeavor. However, videotapes of family
      and social activities can be analyzed using the frame isolating technique of
      video image capture by inexpensive means. A rare skeletal Class III malocclusion
      and dental peculiarities in a decomposing 3-year old lacking a clinical history
      were compared to videotapes taken of a suspected victim shortly prior to her
      disappearance. Overlaying transparent dental tracings from digitized skeletal
      remains onto selected frames of the videotape (and reversing this process)
      produced the identification and hastened the entire investigation.

PMID- 9144938
TI  - Defining microsatellite alleles by genotyping global indigenous human populations
      and non-human primates.
AB  - Polymorphisms at variable number of tandem repeat (VNTR) loci have been used in
      forensic science for almost decade. Microsatellite loci, especially tri-, tetra-,
      and pentanucleotide repeat loci, have shown great potential in personal
      identification and paternity testing. In this report, we describe results of
      genotyping three tetranucleotide repeat loci (D5S818, D7S820, D13S317) in 16
      worldwide indigenous human populations and one chimpanzee population which were
      being developed for forensic applications. We demonstrate the utility of typing
      globally diverse populations in defining microsatellite alleles: Specifically (i)
      investigating the measurement errors of each allele using semi-automatic
      genotyping instrumentation and software, (ii) assessing the range of alleles,
      (iii) understanding the extent of allele frequency differences across worldwide
      populations, and (iv) identifying possible anomalous alleles with complex
      structures.

PMID- 9144939
TI  - A pentaplex automated fluorescent typing system for forensic identification and
      French Caucasian population data.
AB  - The polymerase chain reaction (PCR) amplification of short tandem repeat (STR)
      loci has already proven to be a method of choice for large scale typing of DNA
      samples in which the conventional restriction fragment length polymorphism (RFLP)
      technique is ineffective. A quadruplex PCR including HUMvWFA31A, HUMF13A01,
      HUMTH01, and HUMFESFPS STR loci is used successfully for routine forensic
      applications in our laboratory. However, the need to increase the discrimination
      power of the PCR systems used prompted us to develop a second system of a
      pentaplex PCR for the analysis of 4 additional STR loci (HUMD8S1179, HUMD18S51,
      HUMD21S11, and HUMFIBRA) and the sex determination by amplification of a segment
      of the X-Y homologous Amelogenin gene. Allele and phenotype frequencies for these
      4 STR systems were obtained by multiplex amplification, from approximately 200
      randomly selected and unrelated French Caucasian individuals. Statistical
      calculations for these phenotype distributions met expectations for Hardy
      Weinberg equilibrium. Furthermore, the French allelic frequencies of D18S51,
      D21S11, and HUMFIBRA loci were compared with the data obtained by the Forensic
      Science Service (UK) for the British Caucasian population and proved to be
      similar.

PMID- 9144940
TI  - The distribution of the vWF alleles and genotypes in the Palestinian population.
AB  - Short tandem repeat (STR) loci amplified by PCR are known as a useful tool for
      individual identification and paternity testing. Direct PCR amplification from
      small amounts of whole blood is a rapid and convenient method for population
      screening for STR and VNTR markers. The allele frequencies of the vWF locus were
      determined for 127 unrelated Palestinians. Co-dominant segregation was observed
      in 20 mother/child pairs. Nine alleles were observed, with frequencies ranging
      from 0.004 to 0.327. Heterozygosity was 79%, and discrimination power was 0.927.

PMID- 9144941
TI  - PCR-based forensic testing of DNA from stained cytological smears.
AB  - Experiments were performed to evaluate the efficiency of PCR-STR (Short Tandem
      Repeats) and PCR-sequence polymorphisms for the identification of stained pap
      smears and postcoital slides stained with cytological and forensic techniques.
      HLA-DQA1, PolyMarker, Amelogenin, HUMTH01, HUMVWFA31, HUMF13B, and HUMFES/FPS
      were determined. With the exception of the forensic Baecchi stain, all the PCR
      systems gave consistent results in comparison with the reference blood from the
      donors. Cytological stained smears can be important evidence for identification
      in sexual assault cases and in missing person cases.

PMID- 9144942
TI  - Distribution of types for six PCR-based loci; LDLR, GYPA, HBGG, D7S8, GC and HLA
      DQA1 in central Pyrenees and Teruel (Spain).
AB  - The PCR-based DNA loci LDLR, GYPA, HBGG, D7S8, GC and HLA DQA1 are widely used in
      forensic casework analyses. Population data on the distribution of allele
      frequencies are desired to estimate the rarity of a DNA profile. We studied the
      allele distributions at these forensically important DNA markers in two Spanish
      populations (Central Pyrenees and Teruel). Results were in agreement with Hardy
      Weinberg expectations. Furthermore, there was little evidence for departures from
      expectation of independence between loci within the two sample populations. Tests
      for homogeneity were carried out between the two Spanish populations and a U.S.
      Caucasian population.

PMID- 9144943
TI  - Italian population allele and genotype frequencies for the AmpliType PM and the
      HLA-DQ-alpha loci.
AB  - The distribution of six genetic loci analyzed by PCR using the commercial
      AmpliType PM (PolyMarker) kit (Perkin Elmer, Norwalk, CT) was evaluated in 200
      unrelated Italian individuals. The examined loci included: Group-specific
      component (Gc) (1), D7S8 (2), hemoglobin G gammaglobin (HBGG) (3), glycophorin A
      (GYPA) (4), low density lipoprotein receptor (LDLR) (5), and HLA DQ-alpha (6).
      The AmpliType PM Kit analysis is based on the reverse dot blot format and the
      results are interpreted by reading the pattern of blue dots which determine the
      alleles present at each locus. The population data collected allow the
      implementation of AmpliType PM into routine casework.

PMID- 9144944
TI  - An unusual bloodstain case.
AB  - A body was discovered associated with a series of bloodstains on a sunken loading
      ramp of a supermarket. The initial evaluation of the scene by the local police
      determined that the victim was crushed by the rear wheels of an 18-wheel grocery
      truck when it backed down the ramp for a delivery. However, a careful examination
      of the photographs of the scene and the victim revealed that the victim was deal
      and in rigor mortis before the truck entered the ramp. The truck's rear wheels
      never came into contact with the deceased. The truck interacted with the
      decreased and his bicycle to create series of unusual bloodstain patterns.

PMID- 9144945
TI  - Sudden death due to tricuspid valve myxoma with massive pulmonary embolism in a
      15-month old male.
AB  - Myxomas of the tricuspid valve are extremely rare, with only 13 cases reported in
      the world literature. We report the case of a 15-month old male with tricuspid
      valve myxoma and massive myxomatous pulmonary emboli discovered at autopsy.

PMID- 9144946
TI  - Tungsten determination in biological fluids, hair and nails by plasma emission
      spectrometry in a case of severe acute intoxication in man.
AB  - A healthy 19-year-old recruit in a French artillery regiment drank 250 mL of a
      mixture of beer and wine that had rinsed in a hot 155-mm gun-barrel. Fifteen
      minutes later, he complained of nausea followed by seizures. He was comatose for
      24 h, presenting signs of encephalopathy. A moderate renal failure was noted
      initially and worsened to an extensive tubular necrosis with anuria on the day
      after the incident. The first toxicological investigations only showed a 0.31 g/L
      blood ethanol. Then inductively-coupled plasma (ICP) emission-spectrometry
      revealed very high concentrations of tungsten in the "beverage" as well as in
      gastric content, blood and urine (1540 mg/L, 8 mg/L, 5 mg/L, and 101 mg/L,
      respectively). The nature of the metal was confirmed by ICP coupled to mass
      spectrometry. A simple and reliable ICP quantitative assay of tungsten in
      biological fluids, hair and nails was then developed. It showed high blood levels
      (> 0.005 mg/L) until day 13 in spite of six hemodialyses, and in urine until D33.
      Tungsten was also incorporated in hair and nails. To the best of our knowledge,
      such an intoxication has never been reported before though this drinking seems to
      be traditional in the French Artillery. It has probably been favored by the
      unusually high volume of beverage absorbed and by the new alloy of the gun,
      containing tungsten. The clinical evolution was satisfactory over weeks and the
      patient was declared totally cured after five months.

PMID- 9144947
TI  - The Centers for Disease Control and Prevention's Medical Examiner/Coroner
      Information Sharing Program (MecISP)
AB  - In 1986, the Centers for Disease and Prevention established the Medical Examiner
      and Coroner Information Sharing Program (MecISP) with four primary goals: 1) To
      improve the quality of death investigations in the United States and to promote
      more standardized practices concerning when and how to conduct these
      investigations; 2) to facilitate communication among death investigators, the
      public health community, federal agencies, and other interested groups. 3) to
      improve the quality, completeness, management, and dissemination of information
      regarding investigated deaths; and 4) to promote the sharing and use of medical
      examiner/coroner death investigation data. Major MecISP projects have included
      periodic production of a directory of death investigators in the United States
      and Canada, creation of standard and generic death investigation report forms,
      development of death investigation data sets, and collection of death
      investigation data from medical examiner/coroner offices. MecISP also conducts
      site visits to assist in office computerization, supports educational meetings
      and the development of training materials for death investigators, facilitates
      ongoing projects of relevant professional organizations, contributes publications
      to the death investigation literature, conducts surveillance of selected types of
      deaths, and responds to specific inquiries from medical examiners and coroners
      about administrative and practical death investigation issues.

PMID- 9144948
TI  - The impact of homicide trials on the forensic pathologist's time--the Fulton
      County experience.
AB  - Subpoenas received for criminal trials related to homicides in Fulton County
      (Atlanta) Georgia were tracked in a computer database for an 18 month period in
      order to determine the proportion of forensic pathologist worktime required for
      testimony in homicide cases. The number of subpoenas received annually amounted
      to 64% of the average number of homicides occurring annually. Testimony was
      required in about 33% of cases in which a subpoena was received, and, therefore,
      the number of testimony appearances per year was about 21% of the average annual
      number of homicides. Assuming a 40 hour work week for 52 weeks per year and an
      average of 3 hours of time preparing for, traveling to, and testifying in court,
      the time required of the forensic pathologist to testify in homicide trials
      amounted to about 2% of a full-time-equivalent. Although the time required for
      testimony in homicide cases may vary among jurisdictions because of the nature of
      its homicides, distance and travel time to court, and other factors, the data
      presented here may be used to estimate the impact of homicide trial court time on
      forensic pathology practice.

PMID- 9144949
TI  - Endodontics as a dental identification.

PMID- 9144950
TI  - High levels of alpha-amylase in seminal fluid may represent a simple artifact in
      the collection process.

PMID- 9144951
TI  - Anticryptococcal activity by alveolar macrophages from rats treated with
      cortisone acetate during different periods of time.
AB  - The effect of cortisone acetate (CA) treatment on the anticryptococcal activity
      by rat alveolar macrophages (AM) was investigated. The animals received a weekly
      dose of 5 mg CA during 1, 2, 3 or 4 weeks. Following the final dose the AM were
      collected by lung lavage and challenged with Cryptococcus neoformans. Parallel
      experiments with silica particles of a similar size were performed. The
      phagocytic function was assessed using a fluorescence method that distinguishes
      between attached and ingested particles. The oxidative metabolism was studied by
      the nitroblue tetrazolium (NBT) reduction test. The accumulated attachment (a
      measure of the attachment process) of cryptococci and silica particles per AM was
      significantly depressed after the third and fourth week of CA treatment. The
      ingested fraction (a measure of the ingestion process) of cryptococci but not of
      silica particles showed a small but significant decrease after the fourth week.
      The NBT reduction of the unstimulated AM and those stimulated with either the
      cryptococci or silica particles for 24 h was significantly reduced after the
      fourth week of treatment. In conclusion, these results demonstrate that high dose
      CA treatment primarily affects the attachment of the cryptococci to the AM and to
      a lesser extent also the ingestion process. In addition, it decreases the NBT
      reduction by AM in response to the yeast. The impairment of the AM
      anticryptococcal activity by high doses of CA constitutes a risk of dissemination
      of C. neoformans from the lungs.

PMID- 9144952
TI  - Etiology and clinical characteristics of mycotic leukonychia.
AB  - The purpose of the present paper is to add to our understanding of the prevalence
      of mycotic leukonychia. Twenty patients with mycotic leukonychia were studied.
      Leukonychia with atypical characteristics not previously described or with
      discordant characteristics relative to the ones that were responsible of this
      infection were found. Direct microscopic examination and cultures showed that
      Fusarium spp. were the responsible agents in 10% of the cases and that
      dermatophytes were implicated in the other 90%, where Trichophyton rubrum was the
      predominant etiologic agent. In this report we describe the clinical
      characteristics of the nail infections, the probable predisposing causes of the
      disease and the evolution of the cases.

PMID- 9144953
TI  - Utility of Albicans ID plate for rapid identification of Candida albicans in
      clinical samples. Rapid identification of Candida albicans.
AB  - Albicans ID (bioMerieux, Marcy l'Etoile, France) is a ready-to-use medium that
      contains a chromogenic substrate that allows rapid detection and specific
      identification of Candida albicans. We have evaluated its clinical performance by
      culturing 846 clinical specimens from pregnant women and neonates. A 99.2%
      sensitivity and a 100% specificity were observed in the identification of C.
      albicans isolates from primary culture.

PMID- 9144954
TI  - A rapid urease test for presumptive identification of Cryptococcus neoformans.
AB  - A rapid method to evidence urease activity is described. Urea hydrolysis and
      consequent production ammonia are detected by a chemical reaction producing a
      blue phenol compound (indophenol blue). Three hundred and three yeast were
      tested. Out of 107 urease-positive organisms detected by Christensen's Urea Agar
      Test (CUAT) 102 were positive by our method. No false negatives were observed by
      this method when testing 87 Cryptococcus strains. Ths practical screening test
      for presumptive identification of Cryptococcus neoformans is simple, unaffected
      by pH changes and requires 15 minutes to be performed.

PMID- 9144956
TI  - Further studies on Egyptian soil fungi: succession of sugar and osmophilic fungi
      in soil amended with five organic substrates.
AB  - The sugar and osmophilic fungal composition of soils amended with five organic
      substrates (newspaper, orange peel, bromegrass leaves, wheat straw and wood
      sawdust) was estimated after 2, 4, 6, 8 and 10 weeks using the dilution plate
      method on glucose and 50% sucrose Czapek's agar media. Wheat straw was the best
      substrate for total counts of both sugar and osmophilic fungi followed by
      newspaper, bromegrass leaves, wood sawdust and orange peel. Wood sawdust
      supported the highest average counts of total sugar fungi, Fusarium, Mucor,
      Scopulariopsis, Trichoderma and Trimmatostroma spp.; Newspaper, of Aspergillus (8
      spp.), Penicillium (4 spp.) and Chaetomium sp.; bromegrass leaves of Cladosporium
      sp., Humicola sp. and Sporotrichum sp.; orange peel, of Alternaria sp.,
      Circinella sp. and Stachybotrys sp.; and wheat straw, of Botryotrichum sp. and
      Myrothecium sp. Bromegrass leaves and orange peel supported the highest average
      counts of total osmophilic fungi, Aspergillus (10 spp.), Cladosporium sp.
      Paecillomyces sp. and Rhizopus sp.; and of Stemphylium sp., Trichoderma sp.,
      Humicola sp. and Circinella sp. respectively; wheat straw, of Epicoccum sp.,
      Scopulariopsis sp. and Trichothecium sp.; newspaper, of Penicillium (4 spp.) and
      Alternaria sp.; and wood sawdust of Curvularia sp. and Fusarium (3 spp.). The
      best colonizers throughout the experimental periods were Aspergilus and
      Penicillium spp.

PMID- 9144955
TI  - Onychomycosis in Rome, Italy.
AB  - This report presents the results of a study conducted between 1985 and 1994 on
      onychomycosis observed in the city of Rome. Six thousand six hundred and eighty
      eight patients were examined during this period. Among them 1,762 (26.3%) were
      affected by fungal nail infections. Because the etiologic agents could not be
      isolated in 105 cases (6%), the results refer to 1,657 subjects (24.8% of the
      total), presenting with positive microscopic and cultural examinations. Thirty
      eight patients (2.3%) had onychomycosis of both their hands and feet. From an
      etiological point of view, 59.1% of the nail infections were caused by yeasts,
      23.2% were infected with dermatophytes and 17.6% by non-dermatophytic fungi. The
      etiology of onychomycosis of the hands differed from that of the feet. Yeasts
      were primarily responsible for onychomycosis of the hands (86.2%), while
      dermatophytes caused tinea unguium peduum (48%). Fungal fingernail infections by
      Candida spp. were the most common (50.3%), followed by those of the feet by
      dermatophytes (20%). Candida albicans was responsible for 70.6% of the hand
      infections but for only 15.9% of those of the feet. Trichophyton rubrum and T
      mentagrophytes were the most common dermatophytes, mainly causing toenail
      infections (23.4% and 21%, respectively), while Aspergillus spp., Scopulariopsis
      brevicaulis, Acremonium spp. and Aspergillus niger were the most common non
      dermatophytes observed. With regard to sex, the fungal nail infections were more
      widespread in women (72.1%) and in subjects of both sexes over the age of 50.

PMID- 9144957
TI  - First survey on the natural occurrence of Fusarium mycotoxins in Bulgarian wheat.
AB  - Wheat for human consumption (140 samples) was collected after harvest from all
      regions of Bulgaria. The 1995 crop year was characterized by heavy rainfall in
      the spring and summer months. The internal mycoflora of wheat samples was
      dominated by Fusarium spp. and Alternaria spp., and storage fungi were rarely
      present. The samples were analysed for contamination with Fusarium mycotoxins
      deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-AcDON), 15-acetyldeoxynivalenol
      (15-AcDON), T-2 Toxin (T-2), diacetoxyscirpenol (DAS), and zearalenone (ZEA),
      using enzyme immunoassay methods. DON and ZEA were the predominant toxins, with a
      contamination frequency of 67% and 69%, respectively. The average levels of these
      toxins in positive samples were 180 micrograms/kg (DON) and 17 micrograms/kg
      (ZEA), maximum concentrations were 1800 micrograms kg-1 and 120 micrograms kg-1,
      respectively. Acetyl derivatives of DON, namely 3-AcDON and 15-AcDON, were found
      in 2.1% and 0.7% of the samples, at at maximum level of about 100 micrograms kg
      1. Only one sample was positive for T-2 (55 micrograms/kg), DAS was not detected.
      This is the first report about the natural occurrence of a range of Fusarium
      mycotoxins in wheat for human consumption in Bulgaria.

PMID- 9144959
TI  - Overexpression of an endogenous thionin enhances resistance of Arabidopsis
      against Fusarium oxysporum.
AB  - Thionins are antimicrobial proteins that are thought to be involved in plant
      defense. Concordant with this view, we have recently shown that the Arabidopsis
      thionin Thi2.1 gene is inducible by phytopathogenic fungi. Here, we demonstrate
      that constitutive overexpression of this thionin enhances the resistance of the
      susceptible ecotype Columbia (Col-2) against attack by Fusarium oxysporum f sp
      matthiolae. Transgenic lines had a reduced loss of chlorophyll after inoculation
      and supported significantly less fungal growth on the cotyledons, as evaluated by
      trypan blue staining. Moreover, fungi on cotyledons of transgenic lines had more
      hyphae with growth anomalies, including hyperbranching, than on cotyledons of the
      parental line. No transcripts for pathogenesis-related PR-1, PR-5, or the
      pathogen-inducible plant defensin Pdf1.2 could be detected in uninoculated
      transgenic seedlings, indicating that all of the observed effects of the
      overexpressing lines are most likely the result of the toxicity of the THI2.1
      thionin. Our findings strongly support the view that thionins are defense
      proteins.

PMID- 9144958
TI  - A Myb-related transcription factor is involved in the phytochrome regulation of
      an Arabidopsis Lhcb gene.
AB  - We have isolated the gene for a protein designated CCA1. This protein can bind to
      a region of the promoter of an Arabidopsis light-harvesting chlorophyll a/b
      protein gene, Lhcb1*3, which is necessary for its regulation by phytochrome. The
      CCA1 protein interacted with two imperfect repeats in the Lhcb1*3 promoter,
      AAA/cAATCT, a sequence that is conserved in Lhcb genes. A region near the N
      terminus of CCA1, which has some homology to the repeated sequence found in the
      DNA binding domain of Myb proteins, is required for binding to the Lhcb1*3
      promoter. Lines of transgenic Arabidopsis plants expressing antisense RNA for
      CCA1 showed reduced phytochrome induction of the endogenous Lhcb1*3 gene, whereas
      expression of another phytochrome-regulated gene, rbcS-1A, which encodes the
      small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase, was not
      affected. Thus, the CCA1 protein acts as a specific activator of Lhcb1*3
      transcription in response to brief red illumination. The expression of CCA1 RNA
      was itself transiently increased when etiolated seedlings were transferred to
      light. We conclude that the CCA1 protein is a key element in the functioning of
      the phytochrome signal transduction pathway leading to increased transcription of
      this Lhcb gene in Arabidopsis.

PMID- 9144960
TI  - The I2C family from the wilt disease resistance locus I2 belongs to the
      nucleotide binding, leucine-rich repeat superfamily of plant resistance genes.
AB  - Characterization of plant resistance genes is an important step in understanding
      plant defense mechanisms. Fusarium oxysporum f sp lycopersici is the causal agent
      of a vascular wilt disease in tomato. Genes conferring resistance to plant
      vascular diseases have yet to be described molecularly. Members of a new
      multigene family, complex I2C, were isolated by map-based cloning from the I2 F.
      o. lycopersici race 2 resistance locus. The genes show structural similarity to
      the group of recently isolated resistance genes that contain a nucleotide binding
      motif and leucine-rich repeats. Importantly, the presence of I2C antisense
      transgenes abrogated race 2 but not race 1 resistance in otherwise normal plants.
      Expression of the complete sense I2C-1 transgene conferred significant but
      partial resistance to F. o. lycopersici race 2. All members of the I2C gene
      family have been mapped genetically and are dispersed on three different
      chromosomes. Some of the I2C members cosegregate with other tomato resistance
      loci. Comparison within the leucine-rich repeat region of I2C gene family members
      shows that they differ from each other mainly by insertions or deletions.

PMID- 9144961
TI  - Divergence of function and regulation of class B floral organ identity genes.
AB  - Regulatory mechanisms controlling basic aspects of floral morphogenesis seem to
      be highly conserved among plant species. The class B organ identity genes, which
      are required to establish the identity of organs in the second (petals) and third
      (stamens) floral whorls, are a good example of such conservation. This work
      compares the function of two similar class B genes in the same genetic
      background. The DEFICIENS (DEF) gene from Antirrhinum, including its promoter,
      was transformed into Arabidopsis and compared in function and expression with the
      Arabidopsis class B genes APETALA3 (AP3) and PISTILLATA (PI). The DEF gene was
      expressed in the second, third, and fourth whorls, as was PI. Functionally, DEF
      could replace AP3 in making petals and stamens. The DEF gene's AP3-like function
      and PI-like expression caused transformation of fourth-whorl carpels to stamens.
      Like AP3, all aspects of DEF function in Arabidopsis required a functional PI
      protein. Surprisingly, DEF could not replace the AP3 protein in properly
      maintaining AP3 transcripts (autoregulation). Our data allow us to revise the
      current model for class B autoregulation and propose a hypothesis for the
      evolution of class B gene expression in dicotyledonous plants.

PMID- 9144962
TI  - The syntaxin homolog AtPEP12p resides on a late post-Golgi compartment in plants.
AB  - Soluble proteins are transported to the plant vacuole through the secretory
      pathway via membrane-bound vesicles. Targeting of vesicles to appropriate
      organelles requires several membrane-bound and soluble factors that have been
      characterized in yeast and mammalian systems. For example, the yeast PEP12
      protein is a syntaxin homolog that is involved in protein transport to the yeast
      vacuole. Previously, we isolated an Arabidopsis thaliana homolog of PEP12 by
      functional complementation of the yeast pep12 mutant. Antibodies raised against
      the cytoplasmic portion of AtPEP12 have been prepared and used for intracellular
      localization of this protein. Biochemical analysis indicates that AtPEP12 does
      not localize to the endoplasmic reticulum, Golgi apparatus, plasma membrane, or
      tonoplast in Arabidopsis plants; furthermore, based on biochemical and electron
      microscopy immunogold labeling analyses, AtPEP12 is likely to be localized to a
      post-Golgi compartment in the vacuolar pathway.

PMID- 9144963
TI  - Sucrose control of phytochrome A signaling in Arabidopsis.
AB  - The expression of the Arabidopsis plastocyanin (PC) gene is developmentally
      controlled and regulated by light. During seedling development, PC gene
      expression is transiently induced, and this induction can be repressed by
      sucrose. In transgenic seedlings carrying a PC promoter-luciferase fusion gene,
      the luciferase-induced in vivo luminescence was similarly repressed by sucrose.
      From a mutagenized population of such transgenic seedlings, we selected for
      mutant seedlings that displayed a high luminescence level when grown on a medium
      with 3% sucrose. This screening of mutants resulted in the isolation of several
      sucrose-uncoupled (sun) mutants showing reduced repression of luminescence by
      sucrose. Analysis of the sun mutants revealed that the accumulation of PC and
      chlorophyll a/b binding protein (CAB) mRNA was also sucrose uncoupled, although
      the extent of uncoupling varied. The effect of sucrose on far-red light high
      irradiance responses was studied in wild-type, sun1, sun6, and sun7 seedlings. In
      wild-type seedlings, sucrose repressed the far-red light-induced cotyledon
      opening and inhibition of hypocotyl elongation. sun7 seedlings showed reduced
      repression of these responses. Sucrose also repressed the far-red light-induced
      block of greening in wild-type seedlings, and both sun6 and sun7 were affected in
      this response. The results provide evidence for a close interaction between
      sucrose and light signaling pathways. Moreover, the sun6 and sun7 mutants
      genetically identify separate branches of phytochrome A-dependent signal
      transduction pathways.

PMID- 9144964
TI  - Evidence for direct activation of an anthocyanin promoter by the maize C1 protein
      and comparison of DNA binding by related Myb domain proteins.
AB  - The enzyme-encoding genes of two classes of maize flavonoid pigments,
      anthocyanins and phlobaphenes, are differentially regulated by distinct
      transcription factors. Anthocyanin biosynthetic gene activation requires the Myb
      domain C1 protein and the basic helix-loop-helix B or R proteins. In the
      phlobaphene pathway, a subset of C1-regulated genes, including a1, are activated
      by the Myb domain P protein independently of B/R. We show sequence-specific
      binding to the a1 promoter by C1 in the absence of B. Activation is decreased by
      mutations in the C1 DNA binding domain or in a1 sequences bound by C1, providing
      direct evidence for activation of the anthocyanin biosynthetic genes by C1. The
      two C1 binding sites in the a1 promoter are also bound by P. One site is bound
      with higher affinity by P relative to C1, whereas the other site is bound with
      similar lower affinity by both proteins. Interestingly, either site is sufficient
      for C1 plus B/R or P activation in vivo, demonstrating that differences in DNA
      binding affinities between P and C1 are insufficient to explain the differential
      requirement for B. Results of DNA binding site-selection experiments suggest that
      C1 has a broader DNA binding specificity than does P, which may help C1 to
      activate a more diverse set of promoters.

PMID- 9144965
TI  - Photosynthetic electron transport regulates the expression of cytosolic ascorbate
      peroxidase genes in Arabidopsis during excess light stress.
AB  - Exposure of Arabidopsis plants that were maintained under low light (200 mumol of
      photons m-2 sec-1) to excess light (2000 mumol of photons m-2 sec-1) for 1 hr
      caused reversible photoinhibition of photosynthesis. Measurements of
      photosynthetic parameters and the use of electron transport inhibitors indicated
      that a novel signal transduction pathway was initiated at plastoquinone and
      regulated, at least in part, by the redox status of the plastoquinone pool. This
      signal, which preceded the photooxidative burst of hydrogen peroxide (H2O2)
      associated with photoinhibition of photosynthesis, resulted in a rapid increase
      (within 15 min) in mRNA levels of two cytosolic ascorbate peroxidase genes (APX1
      and APX2). Treatment of leaves with exogenous reduced glutathione abolished this
      signal, suggesting that glutathione or the redox status of the glutathione pool
      has a regulatory impact on this signaling pathway. During recovery from
      photooxidative stress, transcripts for cytosolic glutathione reductase (GOR2)
      increased, emphasizing the role of glutathione in this stress.

PMID- 9144966
TI  - Inactivation of the flax rust resistance gene M associated with loss of a
      repeated unit within the leucine-rich repeat coding region.
AB  - The M rust resistance gene from flax was cloned after two separate approaches, an
      analysis of spontaneous M mutants with an L6 gene-derived DNA probe and tagging
      with the maize transposon Activator, independently identified the same gene. The
      gene encodes a protein of the nucleotide binding site leucine-rich repeat class
      and is related (86% nucleotide identity) to the unlinked L6 rust resistance gene.
      In contrast to the L locus, which contains a single gene with multiple alleles,
      approximately 15 related genes occur at the complex M locus, with only one
      encoding the M resistance specificity. The M protein contains two direct repeats
      of 147 and 149 amino acids in the C-terminal part of the leucine-rich region.
      Three mutant alleles of M encoding a product containing a single repeat unit of
      154 amino acids were isolated. The mutant DNA sequences probably occurred by
      unequal intragenic exchange in the coding region of the repeats. The recombinant
      alleles lost M resistance and gained no detectable new resistance specificity.

PMID- 9144967
TI  - A functional homolog of mammalian protein kinase C participates in the elicitor
      induced defense response in potato.
AB  - The elicitor-induced activation of the potato pathogenesis-related gene PR-10a is
      positively controlled by a protein kinase(s) that affects the binding of the
      nuclear factors PBF-1 (for PR-10a binding factor-1) and PBR-2 to an elicitor
      response element (ERE). In this study, we have identified a kinase that has
      properties similar to the conventional isoenzymes of the mammalian protein kinase
      C (PKC) family. the treatment of potato tuber discs with specific inhibitors of
      PKC abolished the elicitor-induced binding of the nuclear factor PBF-2 to the
      ERE. This correlated with a reduction in the accumulation of the PR-10a protein.
      In contrast, treatment of the tuber discs with 12-O-tetradecanoylphorbol 13
      acetate (TPA), an activator of PKC, led to an increase in binding of PBF-2 to the
      ERE and the corresponding increase in the level of the PR-10a protein, mimicking
      the effect seen with the elicitor arachidonic acid. Biochemical characterization
      of proteins extracted from the particulate fraction of potato tubers demonstrated
      that a kinase belonging to the conventional isoforms of PKC is present. This was
      confirmed by immunoprecipitation with antibodies specific to the conventional
      isoforms of human PKC and in-gel kinase assays. The ability of the
      immunoprecipitates to phosphorylate the alpha-peptide (a PKC specific substrate)
      in the presence of the coactivators calcium, phosphatidylserine, and TPA strongly
      suggested that the immunoprecipitated kinase is similar to the kinase
      characterized biochemically. Finally, the similar effects of the various
      modulators of PKC activity on the elicitor-induced resistance against a
      compatible race of Phytophthora infestans implicate this kinase in the overall
      defense response in potato.

PMID- 9144968
TI  - Isolation from coastal sea water and characterization of bacterial strains
      involved in non-ionic surfactant degradation.
AB  - A bacterial community degrading branched alkylphenol ethoxylate (APE) was
      selected from coastal sea water intermittently polluted by urban sewage. This
      community degraded more than 99% of a standard surfactant, TRITON X 100, but I.R.
      analysis of the remaining compound showed the accumulation of APE2 (alkylphenol
      with a two units length ethoxylated chain) which seemed very recalcitrant to
      further biodegradation. Twenty-five strains were isolated from this community,
      essentially Gram negative and were related to Pseudomonas, Oceanospirillum or
      Deleya genera. Among these strains, only four were able to degrade APE9-10
      (TRITON X 100). They were related to the Pseudomonas genus and were of marine
      origin. Pure cultures performed with these strains on TRITON X 100 gave APE5 and
      APE4 as end products. These products were further degraded to APE2 by two other
      strains unable to degrade the initial surfactant.

PMID- 9144969
TI  - Cloning and nucleotide sequence of a D,L-haloalkanoic acid dehalogenase encoding
      gene from Alcaligenes xylosoxidans ssp. denitrificans ABIV.
AB  - We have cloned DNA fragments of plasmid pFL40 from Alcaligenes xylosoxidans ssp.
      denitrificans ABIV encoding a D,L-2-haloalkanoic acid halidohydrolase (DhlIV). A
      6.5-kb EcoRI/SalI-fragment with inducible expression of the halidohydrolase was
      cloned in Pseudomonas fluorescens and Escherichia coli. A 1.9-kb HindII-fragment
      demonstrated expression of the dehalogenase only due to the presence of the
      promoter from the pUC vector in Escherichia coli. The nucleotide sequence of this
      DNA-fragment was determined. It had an open reading frame coding for 296 amino
      acid residues (molecular weight of 32783 D). The dhlIV gene showed sequence
      homology to a short segment of a D-specific dehalogenase (hadD) from Pseudomonas
      putida AJ1, but not to any other known DNA sequences. Restriction enzyme patterns
      indicated similarity between dhlIV and the D,L- isomer specific dehl dehalogenase
      gene from Pseudomonas putida PP3. There are some indications from restriction
      enzyme patterns and initial sequencing data, that a gene encoding a sigma 54
      dependent activator protein, similar to the dehRI regulatory gene from
      Pseudomonas putida PP3 is located upstream of dhlIV. In contrast to DehI,
      dehalogenation of D- or L-chloropropionic acid by the DhlIV-protein leads to
      lactic acid of inverted configuration.

PMID- 9144970
TI  - Degradation of the rubber in truck tires by a strain of Nocardia.
AB  - A strip of tread compound cut from a truck tire was degraded only slightly when
      it was used as the sole growth substrate for a strain of Nocardia. On the
      contrary, its degradation was markedly enhanced by addition of a strip cut from a
      latex glove which the organism readily utilized as a growth substrate. When a
      glove strip was added, the biomass concentration in the experimental flask became
      more than 10-fold higher than the control without a glove strip and the
      colonization of the tire strip was significantly enhanced. After 8 weeks'
      cultivation, about 28% of the tire strip was disintegrated into very small black
      particles (mostly less than 30 microns in diameter) and the weight of the
      remaining unchanged portion of the strip was about 49% of the initial weight.
      Four kinds of truck tire treads were attacked in differing degrees by the
      organism under the same conditions. The treads containing more than 70 phr (parts
      per hundred of rubber) of natural rubber were considerably attacked, while those
      with a natural rubber content of less than 55 phr were attacked only slightly.
      The microbial activity against the rubber in the side wall of a truck tire was
      relatively high, but the inner liner was hardly attacked and the bead rubber not
      at all.

PMID- 9144971
TI  - Georges Brohee Prize 1996. Major cytochrome P-450 families: implications in
      health and liver diseases.
AB  - Cytochromes P-450 are a superfamily of hemoproteins which represent the main
      pathway for drug and chemical oxidation. This superfamily is divided into
      families, subfamilies and/or single enzymes. The majority of P-450s involved in
      drug metabolism appear to belong to three distinct families termed CYP1, CYP2 and
      CYP3. Numerous invasive and non-invasive methodologies have been developed to
      study these enzymes. Their activities are modulated by genetic and nongenetic
      factors as well as pathological conditions. In this work, the significance of
      genetic and nongenetic control of P-450s activities in normal subjects is
      described. Thereafter, the impact of P-450s on the apparition of liver diseases
      and the effects of liver disease on P-450s activities is emphasized. In
      conclusion, future perspectives on this field are presented.

PMID- 9144973
TI  - [Correlation of prostatic specific antigen, tumor grade, and local stage with
      bone scintigraphy in the staging of patients with prostatic cancer].
AB  - OBJECTIVE: To determine the capacity of PSA, tumor grade and local stage to
      predict the bone scintiscan findings in patients with newly diagnosed, untreated
      prostate cancer. METHODS: We analyzed the records of 189 patients with prostate
      cancer that had been seen at our institution from January, 1993 to September,
      1995. PSA determination was performed prior to biopsy, local staging by DRE or
      transrectal US was done and they had a bone scintiscan before treatment. RESULTS:
      21% of the patients had metastasis. Univariate analysis showed PSA (p < 0.001),
      tumor grade (p = 0.01) and local stage (p = 0.001) independently predicted the
      positive bone scintiscans. However, multivariate regression analysis showed tumor
      grade (rc = 0.05) or stage (rc = 0.07) did not increase the predictive value of
      PSA (rc = 0.22). The highest negative predictive value of PSA [95% (IC95 = 87.5%,
      98.6%)] was obtained when 20 ng/ml was used as cutoff. Therefore 1.4% to 13.5% of
      the patients with bone metastasis could not have been diagnosed without
      scintigraphy. CONCLUSION: Bone scintigraphy should be performed routinely to
      determine the extent of the lesion in patients with prostatic cancer,
      particularly in those patients that are likely to undergo radical treatment.

PMID- 9144972
TI  - Serum aminotransferase levels and histological disease in chronic hepatitis C.
AB  - The reliability of serum aminotransferase (ASAT and ALAT) levels, currently used
      in deciding on performing liver biopsy and to assess interferon therapy in
      chronic hepatitis C has been questioned. In Belgium, interferon therapy is
      actually only reimbursed for treatment of chronic hepatitis C when serum
      aminotransferase levels are more than twice the upper limit of normal. The aim of
      the present study was to assess the relationship between serum aminotransferase
      levels and histological severity of chronic hepatitis C. Sixty-seven liver
      biopsies from 51 different patients with chronic hepatitis C and presenting with
      elevated ASAT and/or ALAT levels, were retrospectively evaluated using the
      original terminology (minimal hepatitis, chronic persistent hepatitis, chronic
      active hepatitis, cirrhosis), the Knodell score and the components of the Bianchi
      Gudat score, where grading (portal inflammation, piecemeal necrosis, intra-acinar
      necrosis and inflammation) and staging components (fibrosis/ cirrhosis) are
      quantitated separately. The correlation between amino-transferase levels measured
      at or near to the biopsy date and histological criteria were evaluated using
      Spearman's rank correlation. About one third of the patients, including patients
      with chronic active hepatitis and cirrhosis, presented with ASAT and ALAT levels
      less than twice the upper limit of normal. ASAT levels correlated with originally
      determined histological severity, the numerical Knodell score and the numerical
      scores for piecemeal necrosis, for intra-acinar necrosis and inflammation and for
      fibrosis in the Bianchi-Gudat score. ALAT levels correlated only with intra
      acinar necrosis and inflammation. It is concluded that limiting interferon
      therapy to patients with aminotransferase levels over twice the upper limit of
      normal excludes a large proportion of patients from potentially curative
      treatment. ASAT levels are more useful than ALAT to assess the histological
      severity of the disease, probably because this mitochondrial enzyme is present in
      higher quantities in the liver as compared to the cytosolic ALAT, and is more
      released when tissue damage is more severe.

PMID- 9144974
TI  - Making a world of difference: nurse practitioners--a global perspective.

PMID- 9144975
TI  - Comparing child-rearing practices in parents of children with cancer and parents
      of healthy children.
AB  - This nonexperimental, descriptive study identified parenting behaviors and
      differences in the reported child-rearing practices between parents of children
      diagnosed with cancer and parents of healthy children. Two groups of parents were
      included: 58 parents of children diagnosed with cancer at a large urban
      children's cancer center and 58 parents of healthy children. The total group of
      parents ranged from 22 to 58 years with 35.7 and 35.9 years as the mean ages of
      the two groups. A variety of races were included among the parents and
      educational backgrounds ranged from high school and vocational to graduate/
      doctoral degrees. Each child with cancer selected a healthy friend of the same
      age, sex, and race who served as their healthy counterpart for this study. Each
      of these child's parents were then involved in the data collection process. Data
      were collected over a 2-month period using the Child-Rearing Practices Report
      (CRPR) in the Q-sort format, in which the parent sorted 91 cards containing 91
      items dealing with child-rearing. Items were compared between the two groups
      using two-tailed t-tests. Using a significance level of alpha = .02, 11
      significant differences were found between the two groups in the domains of
      parental expectations, discipline, expression of emotion, parental concern/worry,
      and overprotectiveness. In conclusion, the primary types of items that shared or
      demonstrated significant differences between the two groups of parents were those
      dealing with discipline and overprotectiveness issues. The items responded to
      most significantly different were, "I tend to spoil my child" and "I worry about
      the health of my child," with the parents of children with cancer consistently
      rating these as more descriptive of them than the parents of healthy children
      did. Finally, this study suggested that the time of the child's diagnosis with
      cancer also affected the parents' reported child-rearing practices.

PMID- 9144976
TI  - Glutamine-supplemented tube feedings versus total parenteral nutrition in
      children receiving intensive chemotherapy.
AB  - Although enteral nutrition is generally advocated in the care of children with
      cancer, those patients receiving intensive chemotherapy alone or in combination
      with bone marrow transplantation often require total parenteral nutrition (TPN).
      Two patients are presented illustrating some differences between enteral and
      parenteral feedings in children receiving intensive chemotherapy. Nasogastric
      glutamine-supplemented tube feedings were well tolerated both in the hospital and
      at home. The cost of care for the enterally supported child was less than one
      third of the TPN-supported child. Although TPN appears to be beneficial in some
      patients with cancer, it is expensive and is associated with several significant
      disadvantages. Among these are an increased incidence of both gram-positive and
      gram-negative infections and an increased incidence of gastrointestinal symptoms.
      Enteral nutrition is less costly than TPN and maintains the structural and
      functional integrity of the intestinal mucosa. The addition of certain substrates
      such as glutamine, arginine and omega-3 fatty acids may improve the body's immune
      response as well. We hypothesize that early glutamine supplemented tube feedings
      in children receiving intensive chemotherapy alone or in combination with bone
      marrow transplantation will result in improved nutrition with fewer infections
      and lower cost than TPN-supplemented patients. In addition, a shorter hospital
      stay and improved quality of life are anticipated.

PMID- 9144977
TI  - An analysis of the concept of hope in the adolescent with cancer.
AB  - Nursing application of the concept of hope in the pediatric oncology clinical
      setting is currently in its infancy. This article presents a systematic analysis
      of the concept of hope for use by the pediatric oncology nurse in the care of the
      pediatric adolescent oncology patient. The literature review addresses health and
      illness states as areas significant to the analysis and application of hope. This
      article defines critical attributes, antecedents, and consequences of hope;
      constructs case examples (a model, a borderline, and contrary cases); includes an
      operational definition of adolescent hopefulness; and summarizes empirical
      referents of hope. Through clinical assessment of hope in the pediatric
      adolescent oncology patient and ongoing research of hope in this population,
      evaluation of the potential benefits of hope to this population's adaptation to
      varying health states will be further demonstrated.

PMID- 9144978
TI  - The needs of parents of pediatric oncology patients during the palliative care
      phase.
AB  - The death of a child is considered one of the greatest stresses a parent can
      experience. It has been suggested that death from childhood malignancies is more
      stressful for parents than death due to other chronic diseases. The purpose of
      this qualitative study is to identify parents' perceptions of their needs while
      their child was dying of cancer. Twelve parents of eight children, who died of
      various types of cancer 1 to 3 years ago, were interviewed by the primary
      investigator. These children died either in hospital or at home. Interviews were
      tape recorded, transcribed and analyzed by the investigators. Three needs were
      identified: (1) The need to have the child recognized as special while retaining
      as much normality within the child's and family's lives as possible; (2) The need
      for caring and connectedness with health care professionals; and (3) The need to
      retain responsibility of parenting their dying child. Findings suggest that
      parental needs are similar regardless of where the death occurred. Implications
      for nursing practice and areas for further research were identified.

PMID- 9144979
TI  - Dexrazoxane (ICRF-187): a cardioprotective agent during anthracycline
      chemotherapy.

PMID- 9144980
TI  - A living legend in pediatric oncology nursing: Genevieve Foley, RN, MSN.
      Interview by Kathy Ruccione and Pamela S. Hinds.

PMID- 9144981
TI  - Enough trust to talk about coffins.

PMID- 9144982
TI  - Doctors jump to medical Web sites via MSMSNET.

PMID- 9144983
TI  - Organized medicine physicians' best advocate. What role can collective bargaining
      play for physicians?

PMID- 9144984
TI  - Representative Joseph Palamara. Medicaid managed care tops House Health Policy
      Committee agenda.

PMID- 9144985
TI  - Survey documents medical trends.

PMID- 9144986
TI  - Addressing '93 liability reforms. Observers beginning to see positive effects.

PMID- 9144987
TI  - Reforms should reduce health care costs. Advocates assert 1993 tort reform
      legislation is not to be second-guessed.

PMID- 9144988
TI  - "React, not over-react".

PMID- 9144989
TI  - Organ donor card use by trauma and transplant center personnel.

PMID- 9144990
TI  - The staff and serpent of Asclepius.
AB  - The Staff of Asclepius is one of the most common symbols associated with medical
      profession. The emblem of a single snake and a staff is a true representation of
      medicine in contrast to the caduceus. The origin, meaning, and evolution of the
      Staff of Asclepius is found in antiquity.

PMID- 9144991
TI  - Radiology Quiz #12. Lisfranc fracture-dislocation.

PMID- 9144992
TI  - Virtues and informed consent.

PMID- 9144993
TI  - Covenants not to compete: a trap for Missouri physicians.

PMID- 9144994
TI  - Putting quality improvement into (your) practice. Part Three.

PMID- 9144995
TI  - Are you "missing the boat" in modern asthma therapy?
AB  - I hope this brief update helps you feel more confident that you are current in
      your asthma management practices. I feel that you definitely will be if you
      follow the Pocket Guide for Asthma Management, if you are using inhaled steroids
      in the majority of your patients, and if you are considering the use of long
      lasting B2-agonists and more potent inhaled steroids in at least some of your
      asthma patients who reach steps three and four of therapy. Continue to be
      vigilant for further progress in asthma management. Best wishes for 1997 in your
      professional lives and specifically in managing your asthma patients.

PMID- 9144996
TI  - Risk assessment of fungi reported from humans and animals.
AB  - A classification of fungi into biosafety categories is proposed, and the criteria
      for attribution to biosafety levels (BSL) are briefly discussed. The list differs
      from previous publications on this topic mainly by stressing (ecological)
      criteria derived from the fungi rather than host factors, and in including all
      species accepted in the recent medical literature.

PMID- 9144997
TI  - Liposomal amphotericin B as early empiric antimycotic therapy of pneumonia in
      granulocytopenic patients.
AB  - Twenty-three neutropenic patients with haematological malignancies and febrile
      pulmonary infiltrates were empirically treated with liposomal amphotericin B
      (AmBisome) in addition to broad-spectrum antibiotics. AmBisome was given on
      alternate days in two different dosages: 3 mg kg-1 in patients with pneumonia but
      without radiological signs or other evidence of Aspergillus infection and 5 mg kg
      1 in pneumonia patients with suspected Aspergillus infection. The main objectives
      of this study were to compare the response and lethality of pneumonias treated
      early with empirically AmBisome with a historical group (treatment with
      conventional amphotericin B only in case of proven/highly probable aspergillosis)
      and to investigate the tolerability and efficacy of AmBisome 5 mg kg-1 in cases
      of proven/probable aspergilloses. Six out of seven (86%) patients without
      initially suspected aspergilloses receiving AmBisome 3 mg kg-1 responded
      completely. Twelve out of 16 patients with initial radiological signs of
      aspergillosis receiving AmBisome 5 mg kg-1 were evaluable. Body temperature
      normalized in 10/12 (83%) patients; eight experienced complete and two partial
      regression of their infiltrations and 9/10 patients with proven/probable
      aspergillosis responded. Acute AmBisome-related reactions were seen in three
      patients from each group; loss of potassium was noted in five subjects in each
      group and slightly increased plasma creatinine was found in two patients in the 5
      mg kg-1 group. Altogether, the response of all pneumonia patients treated with
      early empirical AmBisome compared with the historical group was 17/19 vs. 49/72
      (89% vs. 68%, NS); among those with proven/probable aspergilloses 11/12 vs. 7/17
      (92% vs. 41%, P = 0.008) patients responded. Pneumonia lethality was 1/19 in the
      AmBisome-treated patients compared with 23/72 in the historical group (5% vs.
      32%, P = 0.01); and among those with proven/probable aspergilloses it was 1/12
      vs. 10/17 (8% vs. 59%, P = 0.008). In conclusion, early empiric treatment with
      AmBisome 3 mg kg-1 and 5 mg kg-1 on alternate days was well tolerated and greatly
      reduced the lethality of proven/probable Aspergillus pneumonias.

PMID- 9144998
TI  - Specific antibody detection in human aspergillosis: a GEMO* multicentre
      evaluation of a rapid immunoelectrophoresis method (Paragon). Group d'Etude des
      Mycoses Opportunistes.
AB  - A new immunoelectrophoresis system, the Paragon system, was evaluated in three
      different hospital centres with the aim of improving standardization of the
      serodiagnosis of human aspergillosis. To select the most efficient antigen,
      various commercial and home-made antigens were first tested on 19 sera from 19
      patients with highly probable aspergillosis. The value measured using the Paragon
      anti-Aspergillus antibody detection system was then compared with the results
      obtained by conventional serological diagnostic methods (conventional
      immunoelectrophoresis, enzyme linked-immunosorbent assay, indirect
      immunofluorescence): this step was performed using the first 19 sera as well as
      16 other sera from 13 patients with suspected aspergillosis. Concordant results
      were obtained in 28 cases. The discrepancies observed with seven sera were
      probably related to differences in the nature of the antigens. Paragon
      immunoelectrophoresis proved to be a practicable technique requiring only a small
      amount of serum and giving results within a shorter time than competitive methods
      (24-48 h). Its major drawbacks compared with conventional immunoelectrophoresis
      are some difficulties in reading, fewer precipitin lines and the relatively high
      cost of routine analysis.

PMID- 9144999
TI  - Characterization of Aspergillus isolates by pyrolysis mass spectrometry.
AB  - Pyrolysis mass spectrometry (PYMS) is a useful typing method for many bacterial
      and Candida species. We attempted to type Aspergillus spp. by PYMS. Four distinct
      A. fumigatus isolates could not be distinguished from each other, whereas one A.
      niger and one A. terreus could. Poor reproducibility was shown using multiple
      identical cultures of a single A. fumigatus isolate and several isolates of the
      same DNA type. PYMS is obviously an unsuitable typing method for Aspergillus spp.

PMID- 9145000
TI  - Allergic fungal sinusitis: clinicopathological characteristics.
AB  - Allergic fungal sinusitis is a comparatively new disease entity in paranasal
      sinus mycoses. It is not a very rare condition, but diagnosis is difficult to
      establish. Of 28 consecutive cases of allergic nasal polyposis during a 2-year
      period, 11 patients had allergic fungal sinusitis and the diagnosis was based on
      the presence of type I hypersensitivity, eosinophilic mucus without tissue
      invasion of fungi on histopathology and detection of septate hyphae on direct
      microscopy. On culture, Aspergillus flavus was isolated from nine patients and A.
      fumigatus and A. niger from one patient each. Among patients with allergic fungal
      sinusitis, five had asthma, four had proptosis, of whom two had impaired vision,
      and all 11 patients had nasal obstruction. Eight patients described a history of
      recurrence. All patients underwent surgical clearance of the diseased sinuses and
      were given post-operative topical steroids to prevent recurrence.

PMID- 9145001
TI  - Chronic bronchopulmonary aspergillosis in a horse with Cushing's syndrome.
AB  - An atypical case of chronic equine bronchopulmonary aspergillosis with an unusual
      hyphal morphology was diagnosed in a horse with Cushing's syndrome. Because of
      the hyphal localization in chronic ectatic bronchi and bronchioles, and
      juxtabronchiolar processes, the observed type of aspergillosis is similar to
      'saprophytic bronchopulmonary aspergillosis' or 'semi-invasive pulmonary
      aspergillosis' in humans. The aetiological diagnosis of aspergillosis was
      accomplished by the application of a panel of monospecific polyclonal and
      monoclonal antibodies in immunohistochemical techniques.

PMID- 9145002
TI  - Evaluation of himachalol in murine invasive aspergillosis.
AB  - Himachalol (a sesquiterpene alcohol) showed low in vitro minimum inhibitory
      concentrations against Aspergillus fumigatus by the macro- and microbroth
      dilution techniques (genometric mean 250 micrograms ml-1 and 46.4 micrograms ml-1
      respectively) compared with saperconazole. Swiss mice treated with the
      phytoproduct (200 mg kg-1, p.o.) once daily for 7 days exhibited a significant (P
      < 0.001) protection (60%) together with an increase in the mean survival time (15
      days) and a reduced CFU (mean log10) burden of A. fumigatus in the kidneys.

PMID- 9145003
TI  - In vitro antifungal activity of the new triazole D0870 against Penicillium
      marneffei compared with that of amphotericin B, fluconazole, itraconazole,
      miconazole and flucytosine.
AB  - The in vitro activity of D0870, a new triazole, was compared with that of
      fluconazole, itraconazole, miconazole, amphotericin B and flucytosine against
      recent clinical isolates of Penicillium marneffei in Thailand. The minimum
      inhibitory concentrations (MIC) values were determined by a microbroth dilution
      method using morpholinopropanesulphonic acid (MOPS)-buffered RPMI-1640 and brain
      heart infusion (BHI) medium. Yeast nitrogen base (YNB) medium with glucose was
      also used for the assay of flucytosine. D0870 was less active against P.
      marneffei than itraconazole, but its activity was similar to that of miconazole,
      superior to that of amphotericin B and markedly superior to that of fluconazole
      and flucytosine. Much lower MIC values of D0870 were observed with BHI medium.

PMID- 9145004
TI  - Primary cutaneous cryptococcosis following trauma of the right forearm.
AB  - A 62-year-old woman with sarcoidosis II, status post systemic steroid treatment,
      developed an inflammatory, infiltrative skin lesion in the area of a traumatic
      haematoma of the right forearm. The clinical appearance at first corresponded to
      bullous erysipelas. Antibiotic therapy, which was instituted immediately, proved
      to be ineffective. A microbiological swab revealed infection with Cryptococcus
      neoformans. A systemic cryptococcosis could be excluded. Therapy with 200 mg
      itraconazole twice daily resulted in a prompt improvement.

PMID- 9145005
TI  - Disseminated mycosis due to Scedosporium prolificans in an AIDS patient with
      Burkitt lymphoma.
AB  - A case of fatal disseminated infection caused by the dematiaceous hyphomycete
      Scedosporium prolificans diagnosed post mortem is reported in a 60-year-old male
      patient with acquired immunodeficiency syndrome who additionally suffered from
      Burkitt's lymphoma. The patient was significantly granulocytopenic following
      aggressive chemotherapy and irradiation. He developed dyspnoea at rest and chest
      pain despite a normal chest radiograph. Fluconazole treatment was carried out
      empirically because no sign of a fungal infection was detected ante mortem,
      either by mycological cultivation or by serological investigation. First post
      mortem examination revealed a disseminated fungal infection involving the central
      nervous system. Scedosporium prolificans was cultured from the kidney, spleen and
      myocardium. In vitro, the fungal isolate was found to be highly resistant to all
      available systemic antimycotics.

PMID- 9145006
TI  - The epidemiology of pityriasis versicolor in Malawi, Africa.
AB  - During a total population survey in 1988 and 1989 in Karonga district, northern
      Malawi, 4915/61735 (8.0%) people examined were found to have extensive pityriasis
      versicolor (PV). An additional 6085 people (9.9%) were diagnosed as having mild
      disease. The highest prevalence rates of extensive and mild PV were found among
      subjects aged 15-24 years. In this age group between 20% and 25% of people had
      extensive PV. Rates were generally higher among males than among females. PV was
      rarely found in prepubertal subjects.

PMID- 9145007
TI  - Tinea axillaris, a variant of intertriginous tinea, due to non-occupational
      infection with Trichophyton verrucosum.
AB  - The term tinea axillaris has been used only a few times in the literature. In
      this paper we describe a male patient with widespread tinea corporis and unguium
      affecting also both axillary regions. Trichophyton verrucosum was isolated as the
      causative agent. The patient admitted to no direct contact with infected animals,
      but had lived in a rural area until a year before the infection became
      widespread. Topical treatment with glucocorticosteroids probably promoted
      propagation over large parts of his body and may have led to the infection of the
      axillary region, an unusual site for fungal infection. Treatment with
      itraconazole over 4 weeks led to complete clearing of all lesions on glabrous
      skin. Thereafter, itraconazole pulse therapy was used to treat the nail
      infection.

PMID- 9145008
TI  - ABO blood groups in relation to the infection rate of dermatophytosis.
AB  - The role of ABO blood groups in the carriage rate of dermatophytosis was studied.
      Blood grouping was done for 108 culture-proven dermatophytosis patients. Forty
      nine patients belonged to blood group A, 54 to blood group O, three to blood
      group B and two to blood group AB. The incidence of dermatophytosis was found to
      be high in patients of blood group O and A. However, chronicity of the disease
      was more frequent in those in blood group A. The control group consisted of 100
      healthy subjects. Sixteen out of 29 control subjects belonging to blood group A
      had a history of skin infections. None of the O blood group control subjects had
      a history of skin infections. Our study suggests that A blood group subjects may
      be prone to chronic dermatophytosis.

PMID- 9145009
TI  - Isolation of fungi from onychomycosis-suspected nails by two methods: clipping
      and drilling.
AB  - We examined 101 nails clinically suspected of onychomycosis by taking specimens
      with two different techniques: clipping and drilling. We then compared the
      mycological results of these two techniques. The microscopic results were
      similar, but culture was more successful with the clipping technique. Twenty
      seven per cent of specimens obtained by clipping were culture positive for
      dermatophytes compared with 20% obtained by drilling and a combined positivity
      rate of 31%.

PMID- 9145011
TI  - Clinical radiology, clinico-radiologic research: a team work.

PMID- 9145010
TI  - Biodegradation of wool by Trichophyton simii and Aspergillus niger.
AB  - The amount of protein released into liquid culture medium and weight loss were
      taken as measures of wool degradation by Trichophyton simii and Aspergillus
      niger. Protein released into the culture medium was observed to be greater after
      T. simii treatment than after A. niger treatment. Sulphitolysis was shown by T.
      simii, whereas it was absent in the case of A. niger, pH was found to be alkaline
      with an increase in soluble protein in the culture medium in the case of both
      uniculture and dual culture. However, both the weight loss of wool and the amount
      of protein released were significantly reduced when both fungi were allowed to
      attack the substrate. The behaviour of these fungi in dual culture reflects their
      antagonistic activities.

PMID- 9145012
TI  - With reference to: RAYS 21,3,1996 venous thromboembolism.

PMID- 9145013
TI  - Technical trends in functional radiology of the lung.
AB  - In functional radiology of the lung, the depiction of subtle details of
      circulatory and bronchial anatomy, is very important. At present, the evolution
      of the radiographic techniques allows to overcome the difficulty in imaging,
      essentially related to the marked difference in density of chest structures,
      producing radiographs optimized to the concomitant representation of the
      parenchyma and higher absorption structures. Main quality factors related to
      radiation beam optimization on one hand and to imaging systems on the other hand,
      are considered with an analysis of the evolution of methods and techniques of
      thoracic radiology.

PMID- 9145014
TI  - Chest radiograph and functional radiology.
AB  - In the course of the years the concept of functional radiology has gradually been
      developed. It represents the integration of chest radiography with some basic
      concepts of respiratory pathophysiology. The correlation between the higher
      vascularization at the bases of lung as compared to the apex with the gravitation
      factor was the initial reference. From this data, combined with physiologic
      parameters, over the years, relatively simple but diagnostically significant
      semeiotic findings were achieved. The different combinations of acquired
      "morphofunctional" signs allow the differential diagnosis in a number of organic
      and hemodynamic alterations, adding to conventional "morphologic" radiology. New
      contributions to the functional radiology of the lung might come from procedures
      as high resolution computed tomography (HRCT) which with the dynamic study
      supplies morphologic and densitometric information to be correlated with changes
      in pulmonary flow and ventilation/perfusion ratio.

PMID- 9145015
TI  - Advances in pulmonary nuclear medicine.
AB  - Nuclear medicine plays a major role in the diagnosis of pulmonary embolism as
      well as in other lung diseases. Important innovations have concerned in recent
      years the equipment and radiopharmaceuticals. In ventilation studies the use of
      technegas, a monodisperse aerosol able to supply images of the same quality or
      even superior to gas images, is widespread in the clinical practice. Significant
      clinical results in the evaluation of acute thromboembolism have been achieved
      with antifibrin monoclonal antibodies and radioactive peptides specific for
      activated platelet receptors. Primary lung cancer and its metastases can now be
      visualized with tracers used for the study of myocardial perfusion (sestaMIBI,
      tetrofosmin) or labeled ocreotide, a molecule able to recognize lung tumors with
      somatostatin receptors. 99mTc-NR-LU-10 Fab immunoscintigraphy was shown to be
      very sensitive for tumors, while the major role of PET in the differential
      diagnosis of solitary pulmonary nodule, in the initial staging and in the
      response assessment to lung cancer therapy, is confirmed. SPECT is widespread in
      the clinical field with the use of 2-3 head gamma cameras and the possible
      combined imaging with CT or MRI. The use of PET with common gamma cameras with
      appropriate collimation systems or coincident recording without collimation is
      being studied. PET is used in the study of tumor metabolism as well as in the
      evaluation of intra-and extravascular lung water, regional blood flow and
      pulmonary vascular permeability. PET studies of vascular lung physiology as well
      as of receptor physiology, amine accumulation and clearance and drug transport to
      the areas of healthy or impaired lung, were also shown to be fundamental.

PMID- 9145016
TI  - Hemodynamic estimation of chronic cor pulmonale by Doppler echocardiography.
      Clinical value and comparison with other noninvasive imaging techniques.
AB  - Pulmonary arterial pressure (PAP) represents an important prognostic factor in
      patients affected by chronic obstructive pulmonary disease (COPD). A noninvasive
      diagnostic approach is offered by several imaging techniques, such as chest X
      ray, nuclear medicine, real-time sonography, color Doppler US, CT and MRI.
      However, at present a quantitative assessment of PAP is not achieved with
      reasonable precision with any of these techniques. Tricuspid regurgitation can be
      estimated by continuous wave Doppler but it may be difficult in patients with
      COPD. On the contrary, the severity of pulmonary hypertension can be accurately
      assessed with pulsed Doppler echocardiography from the subxiphoid region, using a
      general purpose US device. Nineteen adult patients with COPD were studied by
      duplex-Doppler from an oblique subxiphoid approach and right heart
      catheterization. The study was diagnostic in all cases with quality Doppler
      recordings. A significant relationship was found between AcT and pulmonary mean
      or systolic pressure at rest. An accurate prediction of PAP in COPD is possible
      by means of pulsed-Doppler also in low-grade hypertension. This technique is
      considered a simple and reliable adjunct to the noninvasive evaluation of COPD
      and represents a satisfactory alternative to the classical parasternal approach
      preferred by cardiologists but often not suitable for emphysematous patients.
      Radiologists who routinely use a general purpose US device are encouraged to try
      this new technique in the study of heart disease.

PMID- 9145017
TI  - What is "congested" in cardiac failure? A newer approach to plain film
      interpretation of cardiac failure.
AB  - The amount and location of intra- and extravascular fluids varies for the type
      and duration of heart failure. In some instances (acute LHF) pulmonary and
      systemic blood volume actually diminishes, and in others (chronic LHF) pulmonary
      blood volume diminishes at the bases while increasing in the upper lobes. It is
      only in right heart failure that clinically visible "congestion" occurs and the
      phrase congestive failure should be reserved for right heart failure. It is more
      valuable clinically for the film reader to analyze which compartments contain
      increased or diminished fluid and from this analysis, to decide whether the
      patient is in left, right or biventricular failure and whether this is acute or
      chronic. Upper lobe engorgement, (flow inversion) is not caused by basal edema,
      as previously hypothesized, but by reflex vasoconstriction secondary to chronic
      elevation of left atrial pressure. The mechanism is designed to improve left
      atrial function.

PMID- 9145018
TI  - Airway disease: anatomopathologic patterns and functional correlations.
AB  - Airways represent a serial and parallel branched system, through which the
      alveoli are connected with the external air. They participate in the mechanical
      and immune defense against noxious agents, regional flow regulation to optimize
      the perfusion/ventilation ratio and provide lung mechanical support. Functional
      exploration of central airways is based on resistance measurement, flow-volume
      curve or spirometry, while peripheral airways influence parameters as the
      upstream resistance, the slope of phase III nitrogen washout and the residual
      volume. Bronchodynamic tests supply important information on airway reversibility
      and nonspecific reactivity. Anatomopathologic alterations of obstructive chronic
      bronchitis, pulmonary emphysema and bronchial asthma account for their specific
      functional and bronchodynamic alterations. There is a growing interest for
      bronchiolitis in the clinical, radiologic and functional field. This type of
      lesion, always present in COPD, asthma and interstitial disease, becomes relevant
      when isolated or predominant. The most useful anatomofunctional classification
      separates the "constrictive" forms, the cause of obstruction and hyperinflation,
      from "proliferative" forms where an intraluminal proliferation more or less
      extended to alveolar air spaces as in BOOP (bronchiolitis obliterans organizing
      pneumonia) results in restrictive dysfunction. Constrictive bronchiolitis
      obliterans represents a severe and frequent complication of lung and bone marrow
      transplantation. Idiopathic BOOP may occur with cough or flue-like symptoms. In
      other cases, constrictive and proliferative forms may have a toxic (gases or
      drugs), postinfective or immune etiology (rheumatoid arthritis, LES, etc).
      Respiratory bronchiolitis or smokers' bronchiolitis, an often asymptomatic
      lesion, rarely associated to an interstitial lung disease, should be considered
      separately. The relationships between respiratory bronchiolitis, COPD and initial
      centriacinar emphysema is still to be elucidated. The diagnostic combination of
      the more sensitive functional tests with HRCT will allow a better understanding
      of the natural history of the various forms of bronchiolitis.

PMID- 9145019
TI  - Idiopathic interstitial lung disease: anatomoradiologic pathogenesis.
AB  - Interstitial lung disease encompasses a large number of clinical disorders that
      affect the epithelium, the endothelium or both cell surfaces of alveolar wall and
      satellite structures including terminal and respiratory bronchioles. Causative
      factors are over 200 from bacteria, fungi, viruses, protozoans, to collagen
      disease, hypersensitivity and inorganic pneumoconiosis. Clinical and histological
      findings of open lung and transbronchial biopsies from 50 patients are reported,
      18 patients were affected by diffuse alveolar damage (DAD), 15 patients by usual
      interstitial pneumonia (UIP), 8 patients by non specific interstitial pneumonia
      fibrosis (NSIP-F), 9 patients by bronchiolitis obliterans organizing pneumonia
      (BOOP) correlated with conventional chest radiography in 30 patients and with
      HRCT in 31 patients. Interstitial lung disease other than histiocytosis X share
      anatomoradiologic features indicative for activity, chronic progression, chronic
      quiescence, chronic advanced and irreversible disease. In general, the histologic
      features correlate with radiographic patterns and even if radiologic findings do
      not always supply definitive diagnosis, some HRCT patterns are highly suggestive
      and usually classified into 4 categories: normal; with ground glass attenuation;
      linear, nodular or reticulo-nodular; honeycombing, suggestive for end-stage
      fibrosis. Correlation of HRCT with histologic findings in 31 patients with
      idiopathic interstitial fibrosis (IIF) allowed assessment of disease activity,
      follow-up and therapeutic result. HRCT definitely better than conventional
      radiology detects the presence, type and extent of parenchymal alterations,
      differentiating potential reversible lesions (inflammatory) from potentially
      irreversible (fibrotic) lesions. In IIF, for diagnostic accuracy the specimen of
      open lung (the gold standard), transbronchial or video-thoracoscopic biopsy must
      be preoperative, HRCT-assisted and centered on ground glass opacties (or nodules
      in suspected histiocytosis X) since a diagnostically reliable biopsy correlates
      with HRCT morphology of histologic specimen. Interstitial lung disease includes
      benign as well as malignant forms, thus only a multidisciplinary approach can
      prevent long term hazardous effects as severe cor pulmonale or a fatal outcome.
      The histologic HRCT-assisted assessment of "active" lesions is crucial for
      correct careful treatment of these patients.

PMID- 9145020
TI  - High resolution computed tomography (HRCT) and new perspectives in functional
      radiology of the lung.
AB  - Computed Tomography (CT) with the advent of new techniques as high resolution
      computed tomography (HRTC) and spiral CT with 3D reconstructions (3D CT) allows a
      new morphologic-qualitative as well as functional-quantitative evaluation of
      pulmonary perfusion and ventilation. HRCT allows the identification of secondary
      lobule and a detailed morphologic and comparative analysis of minute distal
      anatomical structures with combined densitometric evaluation of lung parenchyma
      on perfusion. In particular, a new, more specific significance could be
      attributed to changes in density of lung parenchyma (mosaic pattern) with
      associated assessment of the vessel number, caliber and distribution, and a
      comparative evaluation of vessels and density between healthy and impaired areas.
      The "optical" HRCT evaluation on serial axial scans in inspiration and expiration
      allows the functional assessment of compartments which require spirometry and
      tests of respiratory function. Spiral CT allows volumetric acquisitions in a
      single breath which can be reconstructed and processed according to single
      requirements. 3D tailored reconstruction of spiral CT exam in maximum inspiration
      and expiration with a dedicated densitometric window (-1024/+ 100 HU) allows the
      calculation of total lung volume (TLV), of both lungs, of a single lung or
      selected sections. With the "air" densitometric window (-1024/-400 HU) the total
      lung capacity (TLC) and residual volume (RV) are calculated. The ratio between
      these values and the corresponding TLV represents the lung aeration index (LAI).
      3D reconstruction with fixed densitometric value corresponding to median air
      density (peak of histogram) allows the scintigraphic-like "alveolographic"
      reconstruction of lung ventilation. Combined 3D CT and HRCT evaluation possibly
      from a single spiral CT exam, is used in the morphologic-functional diagnosis of
      respiratory pathophysiology.

PMID- 9145021
TI  - Personality trait structure as a human universal.
AB  - Patterns of covariation among personality traits in English-speaking populations
      can be summarized by the five-factor model (FFM). To assess the cross-cultural
      generalizability of the FFM, data from studies using 6 translations of the
      Revised NEO Personality Inventory (P.T. Costa & R. R. McCrae, 1992) were compared
      with the American factor structure. German, Portuguese, Hebrew, Chinese, Korean,
      and Japanese samples (N = 7,134) showed similar structures after varimax rotation
      of 5 factors. When targeted rotations were used, the American factor structure
      was closely reproduced, even at the level of secondary loadings. Because the
      samples studied represented highly diverse cultures with languages from 5
      distinct language families, these data strongly suggest that personality trait
      structure is universal.

PMID- 9145022
TI  - More of what? Issues raised by the Fort Bragg study.
AB  - The sobering findings of the Fort Bragg study illustrate why ambitious
      demonstration projects must be combined with objective outcome evaluations. The
      study does suggest that "more is not always better" (L Bickman, 1996), but more
      of what? Little is known about the specific interventions that were combined to
      form the Fort Bragg system of care, so the study does not really reveal what
      failed or what needs to be changed. Moreover, there is no evidence that the
      specific treatments used had any empirical support. Combining and systematizing
      various treatments may not produce improved outcomes if the treatments are not
      effective in the first place. Costly demonstration programs that combine untested
      treatments may be a poor investment. A better strategy may be to develop and test
      an array of well-documented treatments for an array of child and family problems,
      creating the building blocks needed for effective systems of care in the future.

PMID- 9145023
TI  - Interpreting nullity. The Fort Bragg experiment--a comparative success or
      failure?

PMID- 9145024
TI  - Interpreting the Fort Bragg Children's Mental Health Demonstration Project. The
      cup is half full.

PMID- 9145025
TI  - Resolving issues raised by the Fort Bragg evaluation. New directions for mental
      health services research.

PMID- 9145026
TI  - Automation of matrix-assisted laser desorption/ionization mass spectrometry using
      fuzzy logic feedback control.
AB  - Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry is a
      sensitive and versatile method for biomolecular analysis which has potential for
      high-throughput screening in many applications. To obtain mass spectra of optimal
      quality, however, laser fluence is continuously adjusted during data acquisition
      to be close to the threshold level of ion production, requiring a skilled
      operator and several minutes of acquisition time per sample. Using real-time
      fuzzy logic control of the laser fluence, we here demonstrate that the
      acquisition of MALDI spectra can be automated without reduction of data quality.
      The control algorithm evaluates signal intensity and mass resolution of the base
      peak. It then regulates the laser fluence to keep the ion signal intensity within
      the dynamic range of the data acquisition hardware while maintaining high mass
      resolution. This fuzzy logic control system allows unattended data acquisition
      using either static ion extraction or delayed ion extraction MALDI. Even for
      difficult samples such as femtomole-level peptide mixtures, no significant
      reduction in data quality is observed, as compared to manually obtained spectra.
      Automated analysis of 78 chromatographic fractions with high mass accuracy
      demonstrates the utility of the method. The control algorithm has been combined
      with other software modules to completely automate database identification of
      proteins by their peptide mass maps. The success of fuzzy logic in MALDI
      automation suggests wider uses of this technique in mass spectrometry.

PMID- 9145027
TI  - Miniaturized supported liquid membrane device for selective on-line enrichment of
      basic drugs in plasma combined with capillary zone electrophoresis.
AB  - A hollow fiber miniaturized supported liquid membrane (SLM) device for sample
      preparation is connected on-line with capillary electrophoresis and used for
      determination of a basic drug, bambuterol, in human plasma. The analyte is
      extracted from the outside of the hollow fiber (donor) through the liquid
      membrane (pores of the fiber impregnated with organic solvent) into the acceptor
      solution in the fiber lumen. The process is driven by differences in pH between
      the donor and acceptor solution. The whole volume of the acceptor solution can
      then be injected into the CZE capillary by using the double-stacking procedure
      for large volume-injection. Very clean extracts of low ionic strength are
      obtained from the SLM treatment, making this sample pretreatment method
      compatible with the CZE double-stacking procedure, which in turn makes it
      possible to inject large volumes of sample onto the separation capillary. Good
      performance of the whole procedure is demonstrated, and detection limits in the
      low nanomolar range were obtained in spite of the relatively weak UV absorbance
      of bambuterol. Extractions through the miniaturized SLM unit can be performed for
      5-6 h without regenerating the fiber. The regeneration procedure was tested, and
      no relevant changes in the performance of the extraction could be found after
      seven regenerations, allowing the same fiber to be used for a week.

PMID- 9145028
TI  - Development and standardization of an immuno-quantified solid phase assay for HIV
      1 aspartyl protease activity and its application to the evaluation of inhibitors.
AB  - The catELISA technique was modified and standardized for measuring HIV-1 aspartyl
      protease activity and evaluating the potency of synthetic peptide inhibitors.
      This immuno-quantified solid phase assay combines the use of an immobilized C
      terminal biotinylated peptide as substrate, a crude enzyme preparation, and a
      highly specific antiserum elicited against the C-terminal product of the enzyme
      reaction. A standard curve of this C-terminal product was constructed to
      determine the enzyme activity. This assay, which requires less enzyme and
      substrate, is more sensitive than the conventional HPLC method. The amounts of C
      terminal peptide produced in solution as determined from ELISA and HPLC standard
      curves were comparable. Analogues of peptidomimetics designed in our laboratory
      were assayed for their potency to inhibit the enzyme. One of them, H4, which is a
      hydroxyethylamine isostere of the Phe-Pro peptide bond, was a powerful inhibitor.

PMID- 9145029
TI  - Susceptibility of stable flies (Diptera:Muscidae) from southeastern Nebraska beef
      cattle feedlots to selected insecticides and comparison of 3 bioassay techniques.
AB  - Insecticide susceptibility of field populations of stable flies, Stomoxys
      calcitrans (L.), was assayed using 3 exposure techniques: treated filter papers,
      treated glass petri dishes, and topical applications. Both topical applications
      and residual exposure to treated glass surfaces were suitable for testing
      susceptibility of stable flies to permethrin, stirofos, or methoxychlor. Residues
      on filter papers yielded inconsistent results with stirofos and methoxychlor.
      Significant concentration-mortality regression lines were generated with
      permethrin residues on filter papers, but approximately 1,000 times more
      insecticide was required to produce a toxic response when compared with
      permethrin residues on glass. Because of higher variability in response and the
      greater amount of insecticide required, residues on filter papers do not appear
      appropriate to test insecticide susceptibility in stable flies. Paired
      comparisons of field (F) and susceptible (S) stable flies resulted in field to
      susceptible ratios significantly > 1.0 only when the flies were treated
      topically, which suggests that topical application is more sensitive than
      residues on glass for the insecticides tested. Topical treatment with permethrin
      resulted in one FS(LD90) of 1.8-fold. Topical treatment with methoxychlor
      resulted in one FS(LD90) of 3.4-fold. However, the magnitude of these ratios is
      not larger than the significant differences observed within the susceptible
      laboratory colony from one generation to another. Intense exposure to
      insecticides is not known to have occurred in these field populations, indicating
      that the observed differences are the result of natural variation among stable
      fly populations and unrelated to prior selection with insecticides.

PMID- 9145030
TI  - Reversal of low-level resistance to Bacillus sphaericus in a field population of
      the southern house mosquito (Diptera:Culicidae) from an urban area of Recife,
      Brazil.
AB  - A larval population of Culex quinquefasciatus Say from an urban area (Coque) of
      Recife, Brazil, submitted to selection with Bacillus sphaericus Neide for a 26-mo
      trial, was 10 times less susceptible to B. sphaericus and slightly more
      susceptible to Bacillus thuringiensis israelensis, compared with untreated
      populations. The low-level resistance to B. sphaericus was unstable in the
      absence of selection pressure. The LC50 of B. sphaericus to the Coque population
      declined gradually and attained a susceptibility level similar to that observed
      in a laboratory control colony 16 mo after the treatment period was interrupted.
      In parallel to the recovery of B. sphaericus susceptibility. Coque larvae also
      were as susceptible as laboratory larvae to B. thuringiensis israelensis.

PMID- 9145031
TI  - Biological effects of canatoxin in different insect models: evidence for a
      proteolytic activation of the toxin by insect cathepsinlike enzymes.
AB  - Canatoxin is a toxic protein isolated from the jackbean, Canavalia ensiformis.
      The toxin injected intraperitoneally is lethal for mice and rats; however, it is
      inactive if given orally. In this study, Manduca sexta (L.) (Lepidoptera),
      Schistocerca americana (Drury) (Orthoptera), Drosophila melanogaster (L.)
      (Diptera), Aedes aegypti (L.) (Diptera), Rhodnius prolixus (Stal) (Hemiptera),
      and Callosobruchus maculatus (F.) (Coleoptera) were fed on canatoxin-containing
      diets. No effects were seen in M. sexta, S. americana, D. melanogaster, or A.
      aegypti. No traces of canatoxin were found in their feces, suggesting that the
      protein was digested completely by these insects, which characteristically have a
      trypsin-based digestion. In contrast, canatoxin was lethal for insects displaying
      cathepsin-based digestion. Thus, for C. maculatus, a diet containing 0.25% wt:wt
      canatoxin caused complete inhibition of larval growth. When R. prolixus were fed
      on canatoxin, 2 effects were seen: impairment of water excretion and increased
      lethality 48-96 h after feeding. The lethal effect of canatoxin in R. prolixus
      was blocked partially or completely when the digestion of the toxin by R.
      prolixus midgut enzymes was impaired. The data showed that canatoxin is highly
      toxic when ingested by some species of insects but not affecting others, probably
      in correlation with the characteristics of the digestive process of the insect.

PMID- 9145032
TI  - Parameters influencing potency of Bacillus thuringiensis var. israelensis
      products.
AB  - Bioassays of products based on Bacillus thuringiensis var. israelensis have been
      carried out according to standard protocols. These analyses revealed that the
      slopes of the log-probit transformed concentration mortality curves of various
      products were different from that of the international standards (IPS82 for B.
      thuringiensis israelensis). For statistical reasons, this invalidates the tests.
      Products giving various slopes of the concentration mortality curves will obtain
      different potencies when estimated at a LC90 level than when estimated at LC50
      level, as normally done. The LC90 level is probably more relevant for the field
      effect. Changing the median particle size of a product in a non destructive way
      results in change of slope and LC50 and thereby potency. Therefore, potency of a
      product as measured in these bioassays is not just a measure of the quantity of
      B. thuringiensis israelensis crystal protein present, but a function of product
      parameters like median particle size. Biochemical methods for quantification of
      toxin can therefore not relate simply to potency of the products obtained with
      this method. It is suggested that standard protocols for bioassay may be changed
      to assure equal particle size of products and samples to obtain parallel dose
      response.

PMID- 9145033
TI  - New insights into mechanisms of allograft rejection.
AB  - Understanding of the molecular basis of organ allograft rejection has increased
      tremendously in the past decade. Insight into the nature of the alloantigen and
      the mechanisms underlying T cell recognition, activation, and differentiation
      provide novel targets for immunotherapy. Appreciation of the role that peptides
      present in the human leukocyte antigen groove play in allorecognition provides a
      new target for synthetic peptide therapy. Elucidation of signal transduction
      pathways downstream from the T-cell receptor helps to explain the mechanism of
      action of immunosuppressive agents and impacts the design of new drugs. An
      understanding of the role of costimulatory molecules, such as CD28, has given
      rise to new therapies, such as CTLA4-Ig. Information about the mechanisms of
      cytotoxicity, chemoattraction, and vascular biology similarly has provided new
      targets for rational drug design. This article highlights new insights into the
      mechanism of allograft rejection relevant to the design of new immunotherapies.

PMID- 9145035
TI  - Immunobiology of sensitization in transplant recipients.

PMID- 9145034
TI  - Clinical application of molecular biology: a study of allograft rejection with
      polymerase chain reaction.
AB  - This article explores the clinical usefulness of reverse transcriptase-polymerase
      chain reaction in organ graft recipients. In this study, reverse transcriptase
      polymerase chain reaction was used to identify intrarenal expression of cytotoxic
      attack molecules (granzyme B and perforin) and immunoregulatory cytokines (IL-2,
      IL-4, IL-10, IFN-gamma, and TGF-beta 1) in human renal allograft biopsies. The
      biopsies (n = 127) were classified using the Banff criteria, and intrarenal gene
      expression was correlated with the histologic diagnosis. Molecular analyses
      revealed that intragraft display of mRNA encoding granzyme B, IL-10, or IL-2 is a
      correlate of acute rejection, and intrarenal expression of TGF beta 1 mRNA is a
      correlate of chronic rejection. In addition to demonstrating differential and
      highly selective intragraft gene expression during rejection, these data suggest
      that therapeutic strategies directed at the molecular correlates of rejection
      might refine existing antirejection strategies.

PMID- 9145036
TI  - Clinical relevance of anti-HLA antibodies pre and post transplant.
AB  - Pretransplant histocompatibility testing seeks to select compatible donor
      recipient pairs for transplantation. Sera from prospective renal transplant
      recipients are screened for the presence of human leukocyte antigen (HLA)
      antibodies to determine humoral alloimmunization. Present techniques screen
      patient sera using a complement-dependent cytotoxicity assay and express the
      results as percent of panel reactive antibody (PRA). However, the standard assay
      suffers because it needs viable target cells, a variable sensitivity of cells for
      complement, subjective evaluation, a lack of standardized methodology, and a
      variable correlation with clinical outcomes. Alternatively, an enzyme-linked
      immunosorbent assay (ELISA) methodology can detect IgG anti-HLA reactivity based
      on the binding of immunoglobulin to soluble HLA class I antigens. This method
      provides increased objectivity and reproducibility, does not require use of
      viable target cells, and most importantly, detects immunoglobulin that is
      reactive to HLA class I antigens. Data discussed herein suggest that identifying
      reactive recipient sera using the enzyme-linked immunosorbent assay (ELISA) (PRA
      STAT, Sang Stat Med, Menlo Park, CA) methodology may be more informative
      clinically than current standard percent of panel reactive antibody (PRA) assays.

PMID- 9145037
TI  - The alloimmunized patient: monitoring and therapeutics.
AB  - The sensitization of renal transplant patients in the form of antihuman leukocyte
      antigen antibodies often constitutes significant risk to allograft function.
      Testing for these antibodies is done before, at the time of, and after renal
      transplantation. Correct interpretation of the results necessitates an
      understanding of the principles of the tests and of the clinical factors in the
      patients, especially those receiving another transplant. Treatment remains
      difficult, although preliminary trials with intravenous gamma globulin have shown
      promising results in some patients.

PMID- 9145038
TI  - Immunosuppressive agents in clinical trials in transplantation.
AB  - Many new agents are in or near clinical trials in organ transplantation. The
      small molecule antibioticlike drugs are inhibitors of key enzymes in T-cell
      signal transduction (calcineurin target of rapamycin [TOR], and inosine
      monophosphate dehydrogenase). Calcineurin inhibitors include cyclosporine
      microemulsion formulation generic cyclosporine preparations, and tacrolimus.
      Rapamycin (also known as sirolimus) acts on target of rapamycin to abrogate
      signals necessary for clonal expansion and is now in phase III. Recent trials of
      mycophenolate mofetil, an inhibitor of inosine monophosphate dehydrogenase, have
      shown that it reduces acute renal graft rejection when used with steroids and
      cyclosporine. New protein reagents in trials include polyclonal antilymphocyte
      antibodies, mouse monoclonal antibodies, "humanized" mouse monoclonals, and
      engineered proteins based on naturally occurring signalling molecules. Humanized
      antibodies against the interleukin-2 receptor are promising because humanized
      antibodies should combine low toxicity with the potential for long-term use.
      Engineered human proteins designed to block costimulatory molecules on antigen
      presenting cells could have similar potential for low toxicity and extended use.
      These agents are designed to reduce acute rejection and the toxicity of the
      existing drugs and eventually improve long-term patient and graft survival. Organ
      transplant practice will probably change considerably as these agents become
      available.

PMID- 9145039
TI  - Leflunomide and malononitrilamides.
AB  - Leflunomide is a new immunomodulatory drug that is effective in experimental
      models of autoimmune diseases and in allo or xenotransplantation. In a phase II
      clinical trial, leflunomide showed high tolerability and efficacy in patients
      with advanced rheumatoid arthritis. The immunomodulatory activity of leflunomide
      is attributed to its primary metabolite A77 1726, which is a malononitrilamide.
      The in vitro and in vivo mechanisms of action of this class of compounds are not
      defined completely. Several malononitrilamide analogues and A77 1726 inhibit T-
      and B-cell proliferation, suppress immunoglobulin production, and interfere with
      cell adhesion. Although no central molecular mechanism of action has been
      proposed to explain all the effects of the malononitrilamides, the inhibition of
      de novo pyrimidine biosynthesis and of cytokine- and growth factor receptor
      associated tyrosine kinase activity are leading hypotheses for the effects of A77
      1726 on T- and B-cell proliferation and function. Leflunomide is effective when
      administered in daily dosages of 10 mg and 25 mg to patients with active
      rheumatoid arthritis. The improved efficacy of a 25 mg dose is associated with a
      higher incidence of adverse effects (gastrointestinal symptoms, weight loss,
      allergic reactions, skin rash, and reversible alopecia). Because of the long
      plasma half-life of A77 1726 (11 to 16 days), loading doses are necessary to
      achieve steady state concentrations. Phase III randomized, placebo-controlled
      trials that use daily dosages of 10 mg or 20 mg are under way in the United
      States and Europe to confirm and extend the results of the phase II study.
      Malononitrilamide analogues of A77 1726 are being evaluated for immunosuppressive
      efficacy in preclinical models of transplantation. If these analogues show
      efficacies and therapeutic indexes that are similar to leflunomide in these
      models and that have shorter half-lives than A77 1726 in phase I trials, the
      preclinical and phase I data will be used to select the analogues for phase II
      trials in organ transplant recipients.

PMID- 9145040
TI  - The pathophysiology of chronic rejection.
AB  - The understanding of chronic rejection has been greatly enhanced by the use of
      genetically controlled experimental models using inbred rats. Models that express
      all lesions encountered in human transplants are described. Findings of chronic
      rejection depend on genetic disparity, strength of the immunologic reaction,
      response to injury, and perpetuation of an ischemic state. Lesions of
      vasculopathy and parenchymal cell damage may proceed at different rates, but the
      vasculopathy seems reversible until healing occurs. The experimental models that
      have led us to significant understanding are described herein.

PMID- 9145041
TI  - Chronic allograft failure: the clinical problem.
AB  - Long-term survival statistics for organ allografts have not improved
      substantially over time, despite improved immunosuppression and organ
      preservation and better surgical and perioperative management. Chronic rejection
      is the most important long-term limitation in allografts and increasingly seems
      to be caused by a multifactorial series of antigen-dependent and antigen
      independent factors. Early injury is critical to late events, whether antigen
      driven (early acute rejection episodes and human leukocyte antigen mismatching)
      or antigen independent (ischemia/reperfusion injury and brain death). Ongoing
      alloimmunologic injury to the host and inadequate organ mass functioning (donor
      age, gender, race, and organ size) also seem to be important to this persisting
      process. Associated recipient conditions, which includes hypertension and
      hyperlipidemia, and postoperative complications, which include drug
      nephrotoxicity and infections, may affect this late-phase graft loss. These
      deleterious risk factors for chronic rejection of long-functioning allografts are
      an important subject for future investigation.

PMID- 9145042
TI  - Will tolerance become a clinical reality?
AB  - The goal of transplant physicians is to create a state of antigen-specific
      tolerance in the recipient, whereby the graft is not rejected and the patient
      will not need a lifetime of medical therapy. Although the immunosuppressive
      medications used are effective in lowering the incidence of rejection, they
      produce significant side effects and do not induce a state of transplantation
      tolerance. Progress toward inducing transplantation tolerance has been made in
      animal models, primarily by the exploitation of the natural mechanisms that
      vertebrates have to maintain self-tolerance. These same strategies are being
      employed in clinical trials and consequently are promising and challenging for
      the future.

PMID- 9145043
TI  - Approaching the clinical application of xenotransplantation.
AB  - Interspecies transplantation or xenotransplantation is seen increasingly as a
      potential approach to overcoming the severe shortage of human organs and tissues
      for transplantation. Much has been learned recently about the immunologic hurdles
      of transplanting porcine organs into humans. These hurdles can be addressed, in
      part, by the genetic engineering of donors and by specific therapies directed at
      the salient immune events. As we succeed in dealing with the immunologic aspects
      of xenotransplantation, other issues, including zoonosis, and regulatory aspects
      will need to be addressed.

PMID- 9145044
TI  - Prison AIDS project focuses on peer education.

PMID- 9145045
TI  - Truth lies in the eye of the beholder.

PMID- 9145046
TI  - Lies students tell.

PMID- 9145047
TI  - Lies students tell.

PMID- 9145048
TI  - Lies students tell.

PMID- 9145049
TI  - Lies students tell.

PMID- 9145050
TI  - Needle-stick concerns.

PMID- 9145051
TI  - Childproof caps open Pandora's box.

PMID- 9145052
TI  - Calcium supplementation for the nation.

PMID- 9145053
TI  - Checking random assignment with claims data.

PMID- 9145054
TI  - Guidelines for the diagnosis and management of migraine in clinical practice.
      Canadian Headache Society.
AB  - OBJECTIVE: To provide physicians and allied health care professionals with
      guidelines for the diagnosis and management of migraine in clinical practice.
      OPTIONS: The full range and quality of diagnostic and therapeutic methods
      available for the management of migraine. OUTCOMES: Improvement in the diagnosis
      and treatment of migraine, which will lead to a reduction in suffering, increased
      productivity and decreased economic burden. EVIDENCE AND VALUES: The creation of
      the guidelines followed a needs assessment by members of the Canadian Headache
      Society and included a statement of objectives; development of guidelines by
      multidisciplinary working groups using information from literature reviews and
      other resources; comparison of alternative clinical pathways and description of
      how published data were analysed; definition of the level of evidence for data in
      each case; evaluation and revision of the guidelines at a consensus conference
      held in Ottawa on Oct. 27-29, 1995; redrafting and insertion of tables showing
      key variables and data from various studies and tables of data with
      recommendations; and reassessment by all conference participants. BENEFITS, HARMS
      AND COSTS: Accuracy in diagnosis is a major factor in improving therapeutic
      effectiveness. Improvement in the precise diagnosis of migraine, coupled with a
      rational plan for the treatment of acute attacks and for prophylactic therapy, is
      likely to lead to substantial benefits in both human and economic terms.
      RECOMMENDATIONS: The diagnosis of migraine can be improved by using modified
      criteria of the International Headache Society as well as a semistructured
      patient interview technique. Appropriate treatment of symptoms should take into
      account the severity of the migraine attack, since most patients will have
      attacks of differing severity and can learn to use medication appropriate for
      each attack. When headaches are frequent or particularly severe, prophylactic
      therapy should be considered. Both the avoidance of migraine trigger factors and
      the application of nonpharmacological therapies play important roles in overall
      migraine management and will be addressed at a later date. VALIDATION: The
      guidelines are based on consensus of Canadian experts in neurology, emergency
      medicine, psychiatry, psychology, family medicine and pharmacology, and
      consumers. Previous guidelines did not exist. Field testing of the guidelines is
      in progress.

PMID- 9145055
TI  - Attitudes toward the use of gender-inclusive language among residency trainees.
      The McMaster Residency Training Program Directors.
AB  - OBJECTIVE: To explore postgraduate medical trainees' attitudes toward the use of
      gender-inclusive language. DESIGN: Self-administered questionnaire. SETTING:
      Seven residency training programs at McMaster University, Hamilton, Ont., from
      July 1993 to June 1994. PARTICIPANTS: Of 225 residents in the programs, 186
      responded to the survey, for a response rate of 82.7%. Men and women were equally
      represented among the respondents. OUTCOME MEASURES: Categorization of attitudes
      about the use of language as gender-inclusive or gender-exclusive;
      characteristics predicting a gender-inclusive attitude. RESULTS: Factor analysis
      and Cronbach's alpha (0.90) supported the existence of a construct related to
      attitudes about language use, the poles of which were categorized as gender
      inclusive and gender-exclusive. The authors classified residents with respect to
      their attitudes to language use from their responses to the questionnaire. In
      univariate analyses, sex, residency program and country of graduation
      significantly predicted a gender-inclusive attitude (p < 0.01). Only the first 2
      variables were significant in a multivariate model; residency program explained
      18% of the variance and sex 3%. Residents in obstetrics and gynecology and
      psychiatry had the most gender-inclusive attitudes, whereas residents in surgery
      and anesthesia had the most gender-exclusive attitudes. CONCLUSIONS: Residents'
      values are reflected in the language they choose to use. Language use may provide
      an index of underlying attitudes that may create hostile environments for female
      trainees.

PMID- 9145056
TI  - Medical curricula for the next millenium: responding to diversity.

PMID- 9145057
TI  - Gender sensitivity in medical curricula.
AB  - Both sex--the biologic aspects of being female or male--and gender--the cultural
      roles and meanings ascribed to each sex--are determinants of health. Medical
      education, research and practice have all suffered from a lack of attention to
      gender and a limited awareness of the effects of the sex-role stereotypes
      prevalent in our society. The Women's Health Interschool Curriculum Committee of
      Ontario has developed criteria for assessing the gender sensitivity of medical
      curricula. In this article, the effects of medicine's historical blindness to
      gender are explored, as are practical approaches to creating curricula whose
      content, language and process are gender-sensitive. Specific areas addressed
      include ensuring that women and men are equally represented, when appropriate,
      that men are not portrayed as the prototype of normal (and women as deviant),
      that language is inclusive and that women's health and illness are not limited to
      reproductive function. By eliminating or at least addressing the subtle and often
      unintentional gender stereotyping in lecture material, illustrations and problems
      used in problem-based learning, medical educators can undertake a much-needed
      transformation of curriculum.

PMID- 9145058
TI  - School-based health promotion: the physician as advocate.
AB  - At the August 1995 meeting of the General Council of the CMA, a resolution
      supporting school-based health promotion (comprehensive School Health) was
      adopted. This article briefly reviews the research supporting this integrated
      approach to school and community programs, applies the recommended approach to
      reducing tobacco use and outlines a role for physicians in promoting
      Comprehensive School Health in their communities.

PMID- 9145059
TI  - Courts, licensing bodies turning their attention to alternative therapies.
AB  - The growing interest in alternative medicine has come to the attention of both
      Canadian licensing bodies and the courts. Two recent cases, a disciplinary
      hearing and a medical-malpractice action, illustrate that physicians need to
      understand the range and complexity of issues surrounding nonconventional
      therapies and their clinical use.

PMID- 9145060
TI  - Fatal case of rabies.

PMID- 9145061
TI  - Medical, health-science students bring different perspectives to
      interdisciplinary ethics course.
AB  - The University of British Columbia offers a unique health care ethics course to
      students in 12 disciplines, including medicine. Organizers say the course
      addresses the "traditional separatism" in health-sciences teaching that for too
      long has been characterized by a lack of interdisciplinary collaboration.

PMID- 9145062
TI  - Why should physicians use e-mail?

PMID- 9145063
TI  - Blunt trauma and operative care in microgravity: a review of microgravity
      physiology and surgical investigations with implications for critical care and
      operative treatment in space.
AB  - BACKGROUND: The assembly of the International Space Station in a low earth orbit
      will soon become a reality. The National Aeronautics and Space Administration
      envisions inhabited lunar bases and staffed missions to Mars in the future.
      Increasing numbers of astronauts, construction of high-mass structures, increased
      extra-vehicular activity, and prolonged if not prohibitive medical evacuation
      times to earth underscore the need to address requirements for trauma care in
      nonterrestrial environments. STUDY DESIGN: A search was carried out to review the
      relevant literature in the MEDLINE and SPACELINE databases. All related
      Technical, Corporate, and Flight Test Reports in the KRUG Life Sciences corporate
      library were also reviewed. Bibliographies of all articles were then reviewed
      from these papers to identify additional pertinent literature. Senior Russian
      investigators reviewed the Russian literature and translated Russian publications
      when appropriate. Personal communication and discussion with active microgravity
      investigators and ongoing microgravity research supplemented published reports.
      RESULTS: A large volume of data exist to document the multiple detrimental
      physiologic effects of microgravity exposure on human physiology. Organs systems
      such as cardiovascular, neurohumoral, immune, hematopoetic, and musculoskeletal
      systems may be particularly affected. These physiologic changes suggest an
      impaired ability to withstand major systemic trauma. Observational data also
      suggest adverse changes in numerous aspects of response to wounding and injury,
      and in areas such as the behavior of hemorrhage, microbiologic flora, and wound
      healing. In addition to an increased volume of ongoing and anticipated basic
      science research in microgravity physiology, preliminary studies of clinical
      diagnosis and therapy have been carried out in microgravity and microgravity
      laboratories. The feasibility of a wide range of ancillary critical care
      techniques has been verified in the parabolic flight model of microgravity.
      Although Russian investigators first performed laparotomies on rabbits in
      parabolic flight in 1967, only recently have American investigators demonstrated
      the reproducible feasibility of open and endoscopic surgical procedures under
      general anesthetic in animal models in a microgravity environment. CONCLUSIONS:
      With appropriate instrumentation and personnel, the majority of resuscitative and
      surgical interventions required to stabilize a severely injured astronaut are
      feasible in a microgravity environment. Onboard limitations in mass, volume, and
      power that are ever present in any spacecraft design will limit the realistic
      capabilities of the medical system. Standard proved and tested trauma and
      operative management protocols will constitute the basis for extra-terrestrial
      care. Surgeons should familiarize themselves with the microgravity environment
      and remain active in planning trauma care for the continued exploration of space.

PMID- 9145064
TI  - Pancreatojejunostomy: leakage is a preventable complication of the Whipple
      resection.
AB  - BACKGROUND: Leakage of the pancreaticojejunal anastomosis has been a major
      complication after pancreaticoduodenectomy (Whipple operation), frequently
      reported in an incidence of 5 percent to 15 percent. The most widely used
      techniques of anastomosis have been variations of end-to-end
      pancreaticojejunostomy. Complicating 152 end-to-end anastomoses, done by me
      (including 98 for carcinoma of the pancreas or ampulla), were 5 pancreatic
      anastomotic leaks; the fifth patient died of this complication. STUDY DESIGN: The
      death resulting from a pancreatic anastomotic fistula led me to change my
      technique to an end of the pancreas to side of the jejunum, mucosa-to-mucosa,
      pancreaticojejunostomy (intubated), a modification of the technique described by
      Cattell and used since 1985 by me in 56 consecutive patients. Patients were
      monitored for clinical evidence of a pancreatic fistula, including evaluation of
      amylase content in serum and, in most, in peritoneal drainage. Pancreatography
      through the exteriorized pancreatic catheter was possible if deemed advisable.
      RESULTS: No pancreatic duct was too small or pancreas too soft to permit
      effective anastomosis. No clinical evidence developed of a pancreatic fistula,
      "sentinel bleed," or acute pancreatitis, and no patient was recognized to have a
      high amylase content in the peripancreatic peritoneal drainage. Results of the
      pancreatogram were negative in three patients with peripancreatic infections and
      in one with severe cholestasis. CONCLUSIONS: Although consensus among surgeons
      does not exist as to technique of pancreatic anastomosis, the end-to-side, mucosa
      to-mucosa pancreaticojejunostomy, intubated, has proved safer in my experience
      than end-to-end pancreaticojejunostomy. The experience has led me to believe that
      the technique may reduce the incidence of this fistula and contribute to making
      pancreaticojejunal leakage a preventable complication.

PMID- 9145065
TI  - Jehovah's Witnesses: unique problems in a unique trauma population.
AB  - BACKGROUND: Jehovah's Witnesses can create perplexing treatment problems by their
      refusal of blood transfusions. This dilemma is especially difficult for the
      trauma surgeon faced with critically low hemoglobin levels or life-threatening
      blood loss in an injured Jehovah's Witness. STUDY DESIGN: Retrospective review of
      the records of 58 Jehovah's Witnesses admitted to a single trauma center between
      July 1992 and June 1995. RESULTS: There were 53 blunt and 5 penetrating injuries.
      Four patients (7 percent) received blood transfusions; one received banked blood
      and three received autotransfusions. Two patients were sedated and paralyzed to
      optimize oxygen utilization; one patient received erythropoietin. Eighteen
      patients had a general anesthetic and underwent an operative procedure; one
      underwent controlled hypotensive anesthesia with normovolemic hemodilution. The
      records of 21 patients (36 percent) included documentation of absolute refusal of
      blood or blood products; the exact status of consent for blood transfusion was
      not documented in the records of 33 patients (57 percent). One death and six
      complications occurred, none of which were attributed to acute blood loss or
      anemia. Treatment options and special techniques for the severely anemic patient
      refusing blood transfusions are discussed. CONCLUSIONS: Documentation of
      religious status and beliefs about blood transfusion, as well as knowledge of
      special treatment options available for anemic Jehovah's Witnesses, is necessary
      to provide quality care to this unique trauma population.

PMID- 9145066
TI  - Management of penetrating juxtahepatic inferior vena cava injuries under total
      vascular occlusion.
AB  - BACKGROUND: Juxtahepatic inferior vena cava injuries are often lethal. Various
      operative strategies have been used to improve outcome, but the mortality rate
      reported in the literature is 80 percent or more. The atriocaval shunt has been
      advocated for isolation of bleeding retrohepatic vena cava, but recent reports
      suggest that mortality might be even higher in patients selected for shunting,
      perhaps owing to ongoing hemorrhage because of indecision and delay prior to
      insertion, or to technical difficulty with insertion. A series of patients with
      juxtahepatic inferior vena cava injuries treated successfully with total vascular
      isolation and occlusion were studied. STUDY DESIGN: Consecutive series of 10
      patients with penetrating injuries to the juxtahepatic inferior vena cava were
      treated at an urban, university-affiliated Level I trauma center. A rapid and
      direct approach was used along with isolation techniques similar to those used in
      liver transplantation and elective resection for neoplasm. As resuscitation
      continued, repair of the inferior vena cava was accomplished in a bloodless
      field, created by manual compression of the liver, wide exposure, portal inflow
      occlusion, and proximal and distal control of the inferior vena cava. Aggressive
      fluid resuscitation and transient aortic cross-clamping controlled resulting
      systemic hypotension. RESULTS: Mean injury severity score was 26 and mean
      penetrating abdominal trauma index score was 28. After exposure, three patients
      had tangential injuries controlled by undersewing a partially occluding clamp.
      Subdiaphragmatic aortic cross-clamping was performed if total occlusion of the
      inferior vena cava reduced systolic blood pressure to 60 mm Hg, which was
      necessary in the remaining seven patients. Nine patients survived surgery, and
      seven of nine survived to hospital discharge. One postoperative death was a
      result of multiple organ dysfunction syndrome, and the other of necrotizing
      bacterial pneumonia. CONCLUSIONS: Total vascular occlusion with selective use of
      aortic cross-clamping yielded 70 percent survival in an injury that historically
      has been associated with survival of 20 percent or less. Minimization of visceral
      ischemia is accomplished by occluding the aorta only after complete isolation of
      the inferior vena cava.

PMID- 9145067
TI  - Does lateral lymph node dissection improve survival in rectal carcinoma?
      Examination of node metastases by the clearing method.
AB  - BACKGROUND: The treatment of rectal carcinoma by lateral lymph node dissection
      has risks and benefits. Therefore, we investigated the therapeutic efficacy of
      lateral lymph node dissection. STUDY DESIGN: We studied 198 patients with rectal
      carcinoma who underwent lateral lymph node dissection. Metastases to the lymph
      nodes were examined by the clearing method. The incidence of urinary and male
      sexual dysfunction was determined by measuring the residual urine volume and
      individual interview 1 year after operation. RESULTS: The rate of metastasis to
      lateral lymph nodes was 11.1 percent, and metastasis to the lateral lymph nodes
      occurred more frequently with lower rectal carcinoma classified as pT3 or pT4 in
      the TNM system. The rate of local recurrence was 12.5 percent and the 5-year
      survival rate after curative resection was 70.1 percent. The 5-year survival rate
      in patients with metastasis to the lateral lymph nodes was 25.1 percent, and this
      rate was significantly lower than the 5-year survival rate of 74.3 percent in
      patients without metastasis to the lateral lymph nodes. Urinary dysfunction was
      observed in 67.5 percent of patients, and male sexual dysfunction was found in
      97.4 percent of men younger than 60 years of age with prior sexual ability.
      CONCLUSIONS: The prognosis for patients with metastasis to the lateral lymph
      nodes is poor, and the improvement in survival rate from lateral lymph node
      dissection is minimal.

PMID- 9145068
TI  - Appendicitis in patients with acquired immunodeficiency syndrome.
AB  - BACKGROUND: Previous reports evaluating appendicitis in patients with human
      immunodeficiency virus/ acquired immunodeficiency syndrome have detailed unusual
      pathology, atypical clinical presentations, and poor outcomes. These reports have
      described small groups of patients and are inconsistent with larger surveys.
      STUDY DESIGN: A retrospective design was used to evaluate patients diagnosed with
      human immunodeficiency virus or acquired immunodeficiency syndrome undergoing
      appendectomy from 1986 to 1995. RESULTS: Fifty-five patients were evaluated (mean
      age 33.4 +/- 8.2 years, 98 percent male, 90 percent clinical acquired
      immunodeficiency syndrome, CD4 count 144.45 +/- 34 cells/mL3). Presenting
      symptoms included right lower quadrant pain (91 percent), nausea and vomiting (41
      percent), diarrhea (22 percent), and generalized abdominal pain (24 percent).
      Significant findings on examination included right lower quadrant tenderness (91
      percent), rebound (74 percent), fever (54 percent), abdominal distention (7
      percent), and generalized abdominal tenderness (9.3 percent). Computed tomography
      was performed in 26 percent and findings were suggestive of appendicitis in 93
      percent of cases. Operative findings included acute inflammation (83.3 percent),
      appendiceal rupture (24 percent), gangrene (29 percent), and normal-appearing
      appendices (5.5 percent). Unusual findings included Mycobacterium tuberculosis
      (1.8 percent), atypical mycobacterium (1.8 percent), and chronic appendicitis
      (3.7 percent). Thirty-day survival was 100 percent. Significant postoperative
      fevers were noted in 33 percent and lasted 4.63 +/- 1.2 days. The presence of
      prolonged postoperative fever was linked to lower CD4 counts (p = .05). Follow-up
      (mean time to follow-up, 1,656 +/- 970 days) was complete in 43 percent. Survival
      at follow-up was noted in 57.1 percent (mean length of survival after surgery,
      837 +/- 155 days). CONCLUSIONS: Appendectomy in patients with human
      immunodeficiency virus/acquired immunodeficiency syndrome is associated with
      little morbidity or mortality. Atypical pathology is rarely identified. A higher
      than expected rate of rupture may be linked to delays before hospitalization or
      to impaired immune status.

PMID- 9145069
TI  - The value of somatostatin-receptor scintigraphy in newly diagnosed endocrine
      gastroenteropancreatic tumors.
AB  - BACKGROUND: Conventional imaging techniques do not routinely detect endocrine
      gastroenteropancreatic tumors preoperatively. The purpose of this study was to
      determine whether the new technique of somatostatin-receptor scintigraphy would
      improve the detection rate of these tumors before initial treatment. STUDY
      DESIGN: In a prospective study, 55 patients with a recent diagnosis of endocrine
      gastroenteropancreatic tumors (22 intestinal carcinoids, 17 gastrinomas, 10
      nonfunctioning pancreatic tumors, and 6 insulinomas), were examined with
      somatostatin-receptor scintigraphy, computed tomography, and ultrasonography.
      Results of the three imaging modalities were compared with findings at surgical
      exploration. RESULTS: None of the insulinomas were localized by somatostatin
      receptor scintigraphy, but 4 of 6 insulinomas were detected by computed
      tomography and ultrasonography. Of 17 gastrinomas, 9 were detected by
      somatostatin-receptor scintigraphy; computed tomography and ultrasonography
      localized only 7. Metastases from the gastrinoma were localized by somatostatin
      receptor scintigraphy in all cases; computed tomography and ultrasonography
      detected metastases in only 6 of 9 patients. Nonfunctioning tumors could be
      localized by somatostatin-receptor scintigraphy, computed tomography, and
      ultrasonography in 4, 7, and 8 of 10 cases, respectively. Detection rate for
      corresponding metastases was the same for all three imaging techniques. Primary
      carcinoids were identified by somatostatin-receptor scintigraphy,
      ultrasonography, and computed tomography in 7, 8, and 11 of 22 cases,
      respectively. Extra-abdominal metastases were detected by somatostatin-receptor
      scintigraphy in only 7 of 19 patients. CONCLUSIONS: In patients with insulinomas,
      somatostatin-receptor scintigraphy is not indicated because none of the six
      tumors was imaged. This holds true for nonfunctional pancreatic endocrine tumors
      and their metastases because no advantage for somatostatin-receptor scintigraphy
      was found over computed tomography and ultrasonography. In contrast, somatostatin
      receptor scintigraphy is superior to computed tomography and ultrasonography for
      determining the extent of the disease in patients with gastrinomas or carcinoids.
      The problem of detecting primary tumors in these patients is not solved by
      somatostatin-receptor scintigraphy.

PMID- 9145070
TI  - Axillary lymph node dissection: is it required in T1a breast cancer?
AB  - BACKGROUND: Several authors have questioned the need for axillary lymph node
      dissection in T1a breast cancer (primary tumors 5 mm or less in diameter),
      although current practice typically includes routine axillary lymph node
      dissection. STUDY DESIGN: We retrospectively reviewed the records of 2,242 breast
      cancers in our tumor registries from 1987 to 1994. The incidence of axillary
      lymph node metastases was determined according to primary breast cancer size. The
      objective was to determine the need for axillary lymph node dissection in T1a
      breast cancers, and our data included 74 T1a cancers. Axillary lymph node
      dissection was performed in 66 of these patients. RESULTS: Axillary lymph node
      metastases were found in 3 of 66 cases (4.5 percent). We also reviewed several
      other institutional series of T1a breast cancers and found no statistical
      difference in the reported axillary lymph node metastases and our data (p < .10).
      The combined single-institution data included 256 T1a breast cancers and had a
      3.9 percent incidence of axillary lymph node metastases. The Surveillance,
      Epidemiology, and End Results (SEER) Program of the National Cancer Institute
      published data statistically different from ours. From 1977 to 1982, 339 T1a
      lesions had a 21 percent incidence of axillary lymph node metastases (p < .005),
      and from 1983 to 1987, 1,491 T1a lesions had an 11 percent metastatic rate (p <
      .001). We believe that the SEER data is flawed, because SEER results do not
      require histologic confirmation of axillary lymph node status. CONCLUSIONS: We
      believe the single-institution rate of 3.9 percent axillary lymph node metastases
      in T1a breast tumors results from state-of-the-art breast cancer screening and
      detection of earlier and smaller lesions. Our data support abandoning routine
      axillary lymph node dissection in T1a breast cancer.

PMID- 9145071
TI  - Effect of duration of ampullary gallstone obstruction on severity of lesions of
      acute pancreatitis.
AB  - BACKGROUND: This study was done to determine the effects of duration of
      obstruction on severity of lesions in patients with acute pancreatitis of biliary
      origin. STUDY DESIGN: This case controlled study used patient data collected
      prospectively on protocol during a 27-year period in a university teaching
      hospital. We studied a group of 97 patients with acute pancreatitis, all with an
      impacted stone at the ampulla of Vater at exploration (Group Ob), and a control
      group of 49 patients with acute gallstone pancreatitis who experienced
      spontaneous ampullary disobstruction within 24 hours from the onset of symptoms
      and who showed a patent ampulla at exploration (Group Cont). Duration of
      obstruction was defined as the time elapsed between the onset of symptoms and
      exploration in Group Ob, and from the onset of symptoms until the appearance of
      signs of ampullary disobstruction in Group Cont. Severity of disease in both
      groups was determined by the appearance of the pancreas at exploration. Patients
      in Group Ob were divided into three subgroups according to duration of
      obstruction: under 24 hours, 25 to 48 hours, and more than 48 hours. RESULTS: The
      incidence of severe pancreatic lesions was higher in Group Ob than in Group Cont
      (19.7 percent compared to 6.1 percent, p < .01). Mean duration of obstruction was
      also significantly longer in Group Ob than in Group Cont (42.4 hours compared to
      10.6 hours). In the subgroups of patients whose obstruction lasted under 48
      hours, the incidence of severe lesions was low: in the 24 hours or fewer group,
      severe lesions were observed in 8.1 percent (3 of 37); and in the 25 to 48 hours
      group, the incidence was 10.6 percent (5 of 47). Neither subgroup differed
      significantly from Group Cont (6.1 percent, 3 of 49). When duration of
      obstruction exceeded 48 hours, however, frequency of severe lesions increased
      significantly to 84.6 percent (11 of 13) (p < .001). CONCLUSIONS: The findings in
      this study suggest that duration of ampullary obstruction is a major factor
      determining the severity of pancreatic lesions: severe pancreatic lesions are
      rare in patients whose obstruction lasts not more than 48 hours. In contrast,
      pancreatic necrosis develops in nearly all patients with obstruction beyond 48
      hours. It may be safe to treat patients conservatively during the first day of
      the illness. If obstruction is not resolved by the second day, endoscopic
      retrograde cholangiopancreatography or surgical intervention must be carried out.

PMID- 9145072
TI  - A prospective comparison of laparoscopic exposure techniques for rectal
      mobilization and sigmoid resection.
AB  - BACKGROUND: We determined the efficacy of a pneumoperitoneum and a gasless
      abdominal wall lifting device in providing exposure for low rectal mobilization
      and sigmoid resection in a swine model. The results of these laparoscopic
      techniques were compared with those obtained using standard open surgical
      methods. STUDY DESIGN: We conducted a prospective randomized nonblinded trial.
      Twenty-four adult female pigs were randomized into three groups depending on
      exposure technique: group 1, open (n = 6); group 2, carbon dioxide (n = 6) or
      helium (n = 6) pneumoperitoneum; and group 3, a mechanical abdominal wall lifting
      device (n = 6). A low rectal mobilization and sigmoid resection with a double
      stapled, circular, end-to-end anastomosis was performed in all pigs. In group 2,
      a laparoscopic-assisted approach was used. Parameters assessed included length of
      operation, length of the colonic specimen, number of lymph nodes per specimen,
      and extent of anterior and posterior rectal mobilization (centimeters from the
      anal verge). RESULTS: Operative times were significantly shorter for group 1 than
      for group 2; no significant differences were found between the two laparoscopic
      subgroups. No significant difference was found in length of the colonic specimen
      or in number of lymph nodes harvested for each group. Extent of anterior and
      posterior rectal mobilization was also not significantly different for the three
      groups. Although mean mobilization lengths for each group were not significantly
      different, the range of values was broader in the laparoscopic groups.
      CONCLUSIONS: A comparable mobilization and bowel resection can be performed
      laparoscopically, regardless of the exposure technique used. Gasless laparoscopy
      may prove useful in patients in whom pneumoperitoneum is contraindicated; it will
      not replace pneumoperitoneum as the only method for obtaining laparoscopic
      exposure because of the ease of use and frank superiority of the pneumoperitoneum
      in most circumstances. Abdominal wall lifting devices seem to be a reasonable
      alternative to pneumoperitoneum for sigmoid resection and rectal mobilization.

PMID- 9145073
TI  - A modified stapling technique for esophagojejunostomy after total or proximal
      gastrectomy.
AB  - BACKGROUND: Stapling devices reduce the leakage rate of digestive tract
      anastomoses, but they increase the risk of strictures. We investigated a newly
      modified technique of end-to-end anastomosis stapling in esophagojejunostomy
      after total or proximal gastrectomy. STUDY DESIGN: A modified stapling technique
      (using a stapled anastomosis between esophageal mucosal and intact jejunal
      layers, with hand-sewn seromuscular sutures between the esophagus and jejunum)
      was used in 21 patients (modified group), while a conventionally stapled
      anastomosis was performed in 17 patients (conventional group). The incidence and
      severity of dysphagia and the size of the anastomosis as determined from x ray
      films were compared in the two groups. RESULTS: The modified technique provided
      significantly better results for dysphagia severity than the conventional method
      (p = 0.0025). Most of the patients in the modified group had mild dysphagia, and
      most patients in the conventional group complained of moderate or severe
      dysphagia. In the modified group, the inner diameter of the anastomosis was 12.1
      +/- 2.5 mm, significantly larger than that in the conventional group (10.0 +/-
      1.8 mm; p = 0.009). CONCLUSIONS: The use of our modified stapling technique can
      minimize the risk of anastomotic stricture and the feeling of dysphagia after
      esophagojejunostomy.

PMID- 9145074
TI  - Lest we forget the future...

PMID- 9145075
TI  - Laparoscopic herniorrhaphy.

PMID- 9145076
TI  - A novel technique for simple laparoscopic extracorporeal knot tying.

PMID- 9145077
TI  - Hepatic transplantation using living donors with aberrant hepatic artery.

PMID- 9145078
TI  - Tissue plasminogen activator-biologic perspective for surgeons.

PMID- 9145079
TI  - Hepatitis C virus infection in healthcare workers. Surgical Infection Society.

PMID- 9145080
TI  - Kidney allocation policies.

PMID- 9145081
TI  - Taking steps toward a more diverse association.

PMID- 9145082
TI  - Taking steps toward a more diverse association.

PMID- 9145083
TI  - Nutrition support for children with HIV/AIDS.

PMID- 9145084
TI  - Women in the new world order: where old values command new respect.

PMID- 9145085
TI  - A classification system to evaluate weight maintainers, gainers, and losers.
AB  - OBJECTIVES: To study natural weight changes and to develop a weight
      classification system that can identify weight maintainers, gainers, and losers.
      DESIGN/OUTCOME: A prospective, observational study in which weight changes over
      five annual measurements were evaluated. In the weight classification system
      used, changes greater than 5 lb defined weight maintenance, gain, or loss.
      SUBJECTS/SETTINGS: Subjects were healthy, normal-weight and over weight, men and
      women (mean age = 44.1 +/- 14.1 years) in the Relationships of Energy, Nutrition,
      and Obesity to Cardiovascular Disease Risk Study. Prospective data for 385 of the
      original 508 subjects for whom actual weights were available for each of the 5
      years (1985 to 1990) were used to classify and characterize subjects by weight
      change categories. STATISTICAL ANALYSES: Cross-tabulations (with chi 2 tests) and
      hterarchical log-linear analyses (with partial chi 2 tests) to examine the
      relationships of categorical variables; analyses of variance (with F tests) for
      continuous measures. RESULTS: Over the 4-year interval, 46% of subjects were
      classified as maintainers, 34% as gainers, and 20% as losers. Over shorter 1-year
      epochs, more subjects were maintainers (62%) and fewer subjects were gainers
      (22%) or losers (16%). Maintainers had fewer and smaller magnitudes of weight
      fluctuations and showed fewer deleterious changes in health risk factors than
      gainers. APPLICATIONS: Weight changes of greater than +/-5 lb can classify a
      person as a weight maintainer, or loser. Although annual weight changes were used
      in this study, a weight change of more than 5 lb between any two points in time
      may suggest nonmaintenance of weight or weight instability that needs further
      evaluation.

PMID- 9145086
TI  - Urinary urea nitrogen is imprecise as a predictor of protein balance in burned
      children.
AB  - OBJECTIVE: To compare estimates of protein balance using the urinary urea
      nitrogen method to predict total urinary nitrogen with isotopically derived
      estimates of metabolic protein balance as defined by the difference between rates
      of protein synthesis and breakdown. DESIGN: Prospective, descriptive, repeated
      measures analysis. Urinary urea nitrogen collections were obtained for 8 to 24
      hours before infusion of L-[1-13C] leucine during fed and fasted states.
      SUBJECTS/SETTING: Eight acutely burned pediatric patients consecutively admitted
      to Shriners Burns Institute, Boston Unit, for medical and surgical care of their
      injuries. MAIN OUTCOME MEASURES: The difference between isotopically measured
      rates of protein synthesis and breakdown was used as an index of protein balance
      and compared with estimates of protein balance determined using the urinary urea
      nitrogen method. STATISTICAL ANALYSIS: Least squares regression analysis was used
      to assess the value of urinary urea nitrogen as a predictor of metabolic protein
      balance. Limits of agreements were used to determine bias and precision between
      the two methods. RESULTS: Urinary urea nitrogen was a significant predictor of
      metabolic protein balance (r2 = .77, P < .001). The direction of protein balance
      was the same in 14 of 16 measurements; however, there was significant lack of
      agreement between the two methods as demonstrated by large quantitative
      differences in protein balance. CONCLUSION: Although the urinary-urea-nitrogen
      based estimates of protein balance correlate well with isotopically derived
      protein balance, they are not precise in determining protein balance in seriously
      burned children.

PMID- 9145087
TI  - Longitudinal study of nutrient and food intakes of infants aged 2 to 24 months.
AB  - OBJECTIVE: To determine the nutrient and food intakes of healthy, white infants
      from families of middle and upper socioeconomic status and to compare intakes to
      current recommendations. DESIGN: Using an incomplete random block design, we
      interviewed 98 mother-infant pairs longitudinally when infants were 2, 3, 4, 6,
      8, 10, 12, 16, 20, and 24 months old. Data obtained included 24-hour dietary
      recalls, usual food intake, and food likes and dislikes. SETTING: Interviews were
      conducted in the mother's home by registered dietitians. Subjects resided in two
      urban areas of Tennessee. SUBJECTS: Of the original 98 subjects, 94 completed the
      2-year study. RESULTS: Mean energy and nutrient intakes generally met or exceeded
      the Recommended Dietary Allowance (RDA). Exceptions were zinc and vitamin D,
      which were each below 100% of the RDA at 9 of the 10 data points, and vitamin E,
      which was below the RDA in the infants' second year. Fat intake decreased from
      more than 40% of energy in the first 6 months to 30% to 32% from 10 to 24 months.
      One third of the infants drank reduced-fat milks at 12 months and more than half
      drank them at 24 months. Although infants ate a variety of foods, vegetables
      often were the least favorite foods. A variety of dairy products provided calcium
      for the infant but lacked vitamin D. CONCLUSIONS: Several nutritional issues
      about infant feeding before 2 years of age arose. Low intakes of zinc, vitamin D,
      and vitamin E were observed. In the second year, low fat intake, use of reduced
      fat milks, and dislike of vegetables were areas of concern.

PMID- 9145088
TI  - Influential factors of caregiver behavior at mealtime: a study of 24 child-care
      programs.
AB  - OBJECTIVE: To measure the nutrition knowledge and attitudes of caregivers in
      child-care programs and to observe the behaviors of caregivers as they interact
      with children at mealtime. DESIGN: A nonexperimental research design. Nutrition
      knowledge and attitudes toward nutrition were measured using survey methodology
      designed for this study. Observers measured caregiver behavior by means of
      observation and quantified it using a behavior checklist. Interrater reliability
      was 98%. Instruments were piloted and content validity was established. Using
      Cronbach's alpha, reliability was .69 and .67, respectively. SUBJECTS/SETTING:
      Participants were 113 caregivers in 24 licensed child-care programs in three
      counties in Illinois. STATISTICAL ANALYSES PERFORMED: The independent variables
      (caregiver nutrition knowledge, caregiver nutrition attitudes, years of teaching,
      prior nutrition training, and education level) were correlated to the dependent
      variable (caregiver behavior), using the Pearson product moment correlation. The
      combination of variance from all independent variables was analyzed using the
      general linear regression model. RESULTS: Although caregivers held beliefs that
      should have a positive influence on children's eating behaviors, they
      demonstrated low knowledge of nutrition and displayed behaviors at mealtimes that
      were inconsistent with their beliefs and expert recommendations. Positive
      correlations were found between nutrition knowledge and behavior at mealtime,
      nutrition knowledge and attitudes, and attitudes and caregiver behavior.
      APPLICATIONS: These instruments can be used to assess and teach nutrition
      practices through self-assessment, training, and coursework. Results also begin
      to define the role of the caregiver in children's nutrition practices. Results
      demonstrate that caregiver behavior can be enhanced by addressing nutrition
      knowledge and attitudes.

PMID- 9145089
TI  - Lower-fat menu items in restaurants satisfy customers.
AB  - OBJECTIVE: To evaluate a restaurant-based nutrition program by measuring customer
      satisfaction with lower-fat menu items and assessing patrons' reactions to the
      program. DESIGN AND SETTING: Questionnaires to assess satisfaction with menu
      items were administered to patrons in eight of the nine restaurants that
      volunteered to participate in the nutrition program. One patron from each
      participating restaurant was randomly selected for a semistructured interview
      about nutrition programming in restaurants. SUBJECTS: Persons dining in eight
      participating restaurants over a 1-week period (n = 686). STATISTICAL ANALYSES
      PERFORMED: Independent samples t tests were used to compare respondents'
      satisfaction with lower-fat and regular menu items. Two-way analysis of variance
      tests were completed using overall satisfaction as the dependent variable and
      menu-item classification (ie, lower fat or regular) and one of eight other menu
      item and respondent characteristics as independent variables. Qualitative methods
      were used to analyze interview transcripts. RESULTS: Of 1,127 menu items rated
      for satisfaction, 205 were lower fat, 878 were regular, and 44 were of unknown
      classification. Customers were significantly more satisfied with lower-fat than
      with regular menu items (P < .001). Overall satisfaction did not vary by any of
      the other independent variables. Interview results indicate the importance of
      restaurant during as an indulgent experience. CONCLUSIONS: High satisfaction with
      lower-fat menu items suggests that customers will support restaurant providing
      such choices. Dietitians can use these findings to encourage restaurateurs to
      include lower-fat choices on their menus, and to assure clients that their
      expectations of being indulged are not incompatible with these choices.

PMID- 9145090
TI  - New views on the RDAs for older adults.
AB  - The oldest age category in the 1989 edition of the Recommended Dietary Allowances
      (RDAs) is 51 years and above. Future committees on dietary reference intakes will
      likely define recommendations for age categories older than this. Instead of
      extrapolations from data derived from experiments on younger people, future RDAs
      should be derived directly from experiments on older people. Further, scientists
      are now interested in the amount of the nutrient that it takes to prevent chronic
      diseases from occurring rather than to prevent deficiencies, and this will likely
      influence RDA numbers. A review of past and current data suggests that the
      current RDAs for the elderly are too low for riboflavin, vitamin B-6, folic acid,
      vitamin B-12, vitamin D, and calcium, and are probably too high for vitamin A.

PMID- 9145091
TI  - Weight gain in women diagnosed with breast cancer.
AB  - This review of the literature indicates that weight gain is a common observation
      among women after the diagnosis of breast cancer. Gains in weight range from 0 to
      50 lb and are influenced by menopausal status; nodal status; and the type,
      duration, and intensity of treatment. Weight gain appears to be greater among
      premenopausal women; among those who are node positive; and among those receiving
      higher dose, longer duration, and multiagent regimens. Psychosocial research
      suggests that weight gain has a profoundly negative impact on quality of life in
      patients with breast cancer. Recent findings also suggest that weight gain during
      therapy may increase the risk of recurrence and decrease survival. Although
      weight gain in patients with breast cancer is clinically well appreciated, little
      research has been conducted to investigate the underlying mechanisms of energy
      imbalance. Changes in rates of metabolism, physical activity, and dietary intake
      are all plausible mechanisms and call for more research. Further study will
      provide valuable insight into the problem of weight gain and encourage effective
      interventions to improve the quality and quantity of life for the woman with
      breast cancer. Until more is known, however, dietetics practitioners will have to
      monitor and work individually with patients with breast cancer and use empirical
      approaches to achieve the important goal of weight management.

PMID- 9145092
TI  - Assessment of meal portion, food temperature, and select nutrient content of the
      Hawaii Meals on Wheels program.

PMID- 9145093
TI  - Sorbitol is a possible risk factor for diarrhea in young children.

PMID- 9145094
TI  - Accuracy of self-measurement of waist and hip circumference in men and women.

PMID- 9145096
TI  - Structure and the genome.

PMID- 9145097
TI  - Pushing back the limits of electron cryomicroscopy.

PMID- 9145095
TI  - Monthly calendars as a tool for improving dietary record keeping.

PMID- 9145098
TI  - A short cut for the immune system.

PMID- 9145099
TI  - Picture story. One-armed bandit.

PMID- 9145100
TI  - The serpin-proteinase complex revealed.

PMID- 9145101
TI  - Interaction of Hsp70 chaperones with substrates.
AB  - Determination of the structure of the substrate binding domain of the Escherichia
      coli Hsp70 chaperone, DnaK, and the biochemical characterisation of the motif it
      recognizes within substrates provide insights into the principles governing Hsp70
      interaction with polypeptide chains. DnaK recognizes extended peptide strands
      composed of up to five consecutive hydrophobic residues within and positively
      charged residues outside the substrate binding cavity.

PMID- 9145102
TI  - Specific protein recognition of an mRNA cap through its alkylated base.
AB  - The specific binding of N7-methylguanine cap analogues to the RNA
      methyltransferase VP39 was observed through X-ray crystallography, providing a
      prototypical structure for a complex between a protein and an mRNA 5' cap.

PMID- 9145103
TI  - Structural insights into serpin-protease complexes reveal the inhibitory
      mechanism of serpins.

PMID- 9145104
TI  - Three-dimensional structure of staphylokinase, a plasminogen activator with
      therapeutic potential.
AB  - The three-dimensional structure of staphylokinase has been determined at 1.8 A.
      The puntative site of interaction with plasminogen was identified and epitopes
      were mapped.

PMID- 9145105
TI  - The structural basis for spectral variations in green fluorescent protein.

PMID- 9145106
TI  - Structure determination of yeast cofilin.
AB  - Cofilin, a ubiquitous 15,000 M(r) protein, plays a central role in regulating
      cytoskeletal dynamics. Cofilin binds to actin monomers and filaments, and has a
      pH-dependent actin severing activity. The structure will allow for a detailed
      analysis of cofilin function.

PMID- 9145107
TI  - Crystal structure of the actin-binding protein actophorin from Acanthamoeba.
AB  - Actophorin is a member of the actin-depolymerizing factor/cofilin family. It
      severs actin filaments and sequesters actin monomers. The crystal structure of
      actophorin will help to elucidate actin-ADF/cofilin interactions.

PMID- 9145108
TI  - Structure of human IgM rheumatoid factor Fab bound to its autoantigen IgG Fc
      reveals a novel topology of antibody-antigen interaction.
AB  - Rheumatoid factors are the characteristic autoantibodies of rheumatoid arthritis,
      which bind to the Fc regions of IgG molecules. Here we report the crystal
      structure of the Fab fragment of a patient-derived IgM rheumatoid factor (RF-AN)
      complexed with human IgG4 Fc, at 3.2 A resolution. This is the first structure of
      an autoantibody-autoantigen complex. The epitope recognised in IgG Fc includes
      the C gamma 2/C gamma 3 cleft region, and overlaps the binding sites of bacterial
      Fc-binding proteins. The antibody residues involved in autorecognition are all
      located at the edge of the conventional combining site surface, leaving much of
      the latter available, potentially, for recognition of a different antigen. Since
      an important contact residue is somatic mutation, the structure implicates
      antigen-driven selection, following somatic mutation of germline genes, in the
      production of pathogenic rheumatoid factors.

PMID- 9145109
TI  - Bombyx mori single repeat telomeric DNA sequence forms a G-quadruplex capped by
      base triads.
AB  - A combined NMR-molecular dynamics approach has been applied to determine the
      solution structure of a truncated analogue of the Bombyx mori telomeric d(TTAGG)
      single repeat sequence in Na+ cation-containing aqueous solution. The two-fold
      symmetric four-stranded d(TAGG) quadruplex contains two adjacent
      G(syn).G(syn).G(anti).G(anti) G-tetrads sandwiched between novel (T.A).A triads
      with individual strands having both a parallel and antiparallel neighbour around
      the quadruplex. The (T.A).A triad represents the first experimental verification
      of a base triad alignment which constitutes a key postulate in the recently
      proposed model of triad-DNA. Further, the (T.A).A triad is generated by
      positioning an A residue through hydrogen bonding in the minor groove of a Watson
      Crick T.A base pair and includes a T-A platform related to an A-A platform
      recently observed in the structure of the P4-P6 domain of the Tetrahymena self
      splicing group I ribozyme. The novel architecture of the truncated Bombyx mori
      quadruplex structure sets the stage for the design and potential identification
      of additional base tetrads and triads that could participate in pairing
      alignments of multi-stranded DNA structures during chromosome association and
      genetic recombination.

PMID- 9145110
TI  - Structural similarity between the pocket region of retinoblastoma tumour
      suppressor and the cyclin-box.
AB  - The pocket region of retinoblastoma tumour suppressor (Rb) is essential for
      tumour suppressing activity. The Rb pocket is primarily composed of two domains,
      A and B. We have determined the X-ray crystal structure of domain A (residues 378
      562) at 2.3 A resolution. Domain A consists of nine alpha-helices. The overall
      arrangement of helices in domain A is remarkably similar to the cyclin-box folds
      found in the crystal structures of cyclin A and TFIIB. This structure, along with
      domain B which is predicted to be homologous to the cyclin-box, suggests that the
      Rb pocket is composed of two cyclin-box fold domains. We present the
      structural/functional features of the Rb pocket, and the potential binding region
      for cellular or viral proteins within domain A.

PMID- 9145111
TI  - NMR identification of hydrophobic cavities with low water occupancies in protein
      structures using small gas molecules.
AB  - Magnetization transfer through dipole-dipole interactions (nuclear Overhauser
      effects, NOEs) between water protons and the protons lining two small hydrophobic
      cavities in hen egg-white lysozyme demonstrates the presence of water molecules
      with occupancies of approximately 10-50%. Similarly, NOEs were observed between
      the cavity protons and the protons of hydrogen, methane, ethylene or cyclopropane
      applied at 1-200 bar pressure. These gases can thus be used as general NMR
      indicators of empty or partially hydrated hydrophobic cavities in proteins. All
      gases reside in the cavities for longer than 1 ns in marked contrast to common
      belief that gas diffusion in proteins is not much slower than in water. Binding
      to otherwise empty cavities may be a major aspect of the anesthetic effect of
      small organic gas molecules.

PMID- 9145112
TI  - Oligosaccharide substrate binding in Escherichia coli maltodextrin phosphorylase.
AB  - The crystal structure of E. coli maltodextrin phosphorylase co-crystallized with
      an oligosaccharide has been solved at 3.0 A resolution, providing the first
      structure of an oligosaccharide bound at the catalytic site of an alpha-glucan
      phosphorylase. An induced fit mechanism brings together two domains across the
      catalytic site tunnel. A stacking interaction between the glucosyl residue and
      the aromatic group of a tyrosine residue at a sub-site remote (8 A) from the
      catalytic site provides a key element in substrate recognition; mutation of this
      residue to Ala decreases the Kcat/Km by 10(4). Extrapolation of the results to
      substrate binding across the site of attack by phosphorolysis indicates a likely
      alteration in the glycosidic torsion angles from their preferred values, an
      alteration that appears to be important for the catalytic mechanism.

PMID- 9145113
TI  - Novel structural features of bovine papillomavirus capsid revealed by a three
      dimensional reconstruction to 9 A resolution.
AB  - The three-dimensional structure of bovine papillomavirus has been determined to 9
      A resolution by reconstruction of high resolution, low dose cryo-electron
      micrographs of quench-frozen virions. Although hexavalent and pentavalent
      capsomeres form star-shaped pentamers of the major capsid protein L1, they have
      distinct high-resolution structures. Most prominently, a 25 A hole in the centre
      of hexavalent capsomeres is occluded in the pentavalent capsomeres. This raises
      the possibility that the L2 minor capsid protein is located in the centre of the
      pentavalent capsomeres. Inter-capsomere connections approximately 10 A in
      diameter were clearly resolved. These link adjacent capsomeres and are
      reminiscent of the helical connections that stabilize polyomavirus.

PMID- 9145115
TI  - Patient safety in accredited office surgical facilities.
AB  - The medical profession is besieged by concerns about cost containment. This in
      turn has focused attention on the use of ambulatory surgical facilities. However,
      the costs of hospital outpatient surgery programs usually prevent them from being
      competitive when compared with the costs of using office surgical facilities. To
      address the question of patient safety in office surgical facilities, the
      American Association for Accreditation of Ambulatory Surgery Facilities (AAAASF)
      sent a questionnaire to its accredited facilities. Two-hundred and forty-one
      (57.7 percent) of the 418 accredited facilities returned the anonymous
      questionnaires, a very high response rate. Or interest are the following
      findings: 400,675 operative procedures were reported during a 5-year period.
      Significant complications (hematoma, hypertensive episode, wound infection,
      sepsis, hypotension) were infrequent, occurring in 1 in every 213 cases. Return
      to the operating room within 24 hours and preventive hospitalization were less
      frequent. A death occurred in 1 in 57,000 cases (0.0017 percent). The overall
      risk is comparable in an accredited office (plastic surgical facility) and in a
      free-standing or hospital ambulatory surgical facility. This study documents an
      excellent safety record for plastic surgery done in accredited office surgical
      facilities by board-certified plastic surgeons.

PMID- 9145114
TI  - Ischemia-reperfusion injury in myocutaneous flaps: role of leukocytes and
      leukotrienes.
AB  - Leukotriene B4 is a potent inflammatory mediator that is derived from the 5
      lipoxygenase pathway of arachidonic acid metabolism and that has been implicated
      in the pathophysiology of polymorphonuclear leukocyte-dependent reperfusion
      injury in a variety of organ systems. The objectives of these investigations were
      to determine whether inhibition of leukotriene B4 attenuates postischemic
      polymorphonuclear leukocyte infiltration and subsequent injury in myocutaneous
      flaps. Anesthetized female Yorkshire pigs were randomized to receive normal
      saline (n = 8), the 5-lipoxygenase inhibitor diethylcarbamazine (n = 7), or the
      leukotriene B4 receptor antagonist SC-41930 (n = 7). All animals underwent 6
      hours of rectus abdominis myocutaneous flap ischemia followed by 4 hours of
      reperfusion. In saline-treated controls, flap ischemia was associated with
      massive polymorphonuclear leukocyte infiltration at 1 and 4 hours of reperfusion
      (252 +/- 70 and 619 +/- 137 polymorphonuclear leukocytes per 25 high-power
      fields, respectively). Skeletal muscle neutrophil content was significantly
      attenuated by pretreatment with diethylcarbamazine (72 +/- 29 and 229 +/- 63
      polymorphonuclear leukocytes per 25 high-power fields; p < 0.05) or SC-41930 (25
      +/- 3 and 193 +/- 25 polymorphonuclear leukocytes per 25 high-power fields; p <
      0.05). Wet-to-dry weight ratios of full-thickness flap biopsies were lower in the
      diethylcarbamazine and SC-41930 groups (2.98 +/- 0.15 and 2.90 +/- 0.26,
      respectively) than in the control group (4.13 +/- 0.23; p < 0.01), and mean
      muscle infarct size, as determined by nitroblue tetrazolium staining, diminished
      from 47.6 +/- 11.3 percent in controls to 25.1 +/- 6.5 percent in
      diethylcarbamazine-treated animals and 7.3 +/- 4.8 percent in SC41930-treated
      animals (p < 0.05). These data indicate that leukotriene B4 plays a critical role
      in mediating neutrophil-dependent injury in postischemic skeletal muscle flaps.

PMID- 9145116
TI  - Reconstruction of Tessier no. 4 clefts revisited.
AB  - Atypical craniofacial clefts present a surgical challenge. Little is published
      about their treatment because of their rarity. Such is the nature of Tessier no.
      4 clefts and others with shortened oculoalar and oculo-oral distances requiring
      multiple operative interventions. The soft-tissue abnormalities include a cleft
      of the lip with possible extension into the check, orbital dystopia, and globe
      abnormalities and a decreased oculo-oral distance. Typically, multiple local
      cheek and nasal flaps are used to close the soft-tissue defects, elevate the
      medial canthus, and protect the globe. However, this approach creates traction on
      the lower eyelid, suboptimal location of the scar, and poor color match between
      the flaps. We present two cases of Tessier no. 4 clefts and one case of a
      multiply clefted (Tessier nos. 1/13, 2/12, 3/11) child with the typical
      contracted oculoalar and oculo-oral distances. Reconstruction with a superiorly
      based nasolabial flap transposed 90 degrees under the eye was performed in all
      three as a primary procedure. This technique respects aesthetic units and places
      the resulting scars in less conspicuous areas on the face.

PMID- 9145117
TI  - Craniofacial skeletal fixation using biodegradable plates and cyanoacrylate glue.
AB  - This study examined the feasibility of fixation of craniofacial bone using
      Lactosorb biodegradable plates adhered to bone with butyl-2-cyanoacrylate
      adhesive (Histoacryl) in a pig. The stability and bone-healing characteristics of
      this rigid fixation method were studied and compared with standard rigid fixation
      using metal plates and screws on osteotomy sites in the frontal bones and
      infraorbital rims. Rectangular osteotomies (2.0 x 3.0 cm) were performed on the
      right and left sides of the frontal bone and wedge-shaped osteotomies (1.5 x 1.7
      cm) were made on the left and right infraorbital rims in seven Yorkshire pigs.
      Metal plates were applied with screws to the osteotomies on one side, and the
      other side was fixed with a biodegradable plate and butyl-2-cyanoacrylate. The
      animals were sacrificed at 8 weeks, and both sides were compared biomechanically
      and histologically. Radiographic, biomechanical, and histologic analyses were
      performed to evaluate skeletal stability, contour, accurate positioning of bony
      fragments, bone healing, and maximum torque to failure of the repair sites.
      Clinical and radiographic observations demonstrated stability of the bone
      fragments without any evidence of displacement. According to Student's t test for
      paired data, no statistical difference was found in the maximum torque to failure
      of fragments fixed with biodegradable plates and glue compared with those fixed
      with metal plates and screws (p > 0.05), whether or not a gap existed at the
      osteosynthesis site. Although the sample size was small, no differences were
      noted between the two types of treatment groups. This study demonstrates that
      rigid internal fixation of osteotomized cranial bone fragments using
      biodegradable plates and butyl-2-cyanoacrylate is as effective as metal plate and
      screw fixation in this animal model.

PMID- 9145118
TI  - Osteoblast-directed osteoclast metabolism from patients with premature coronal
      synostosis.
AB  - Osteoclasts were harvested from explants of five patients with premature
      unilateral coronal synostosis and plated on devitalized bovine bone wafers. The
      planar surface areas of resorption lacunae were quantitated by means of light
      microscopy and a digital imaging system. Osteoclasts isolated from involved
      regions of premature synostosis exhibited enhanced resorption when compared with
      osteoclasts isolated from noninvolved cranial bone in the same patients (p <
      0.05). When the involved osteoclasts were exposed to conditioned media from non
      involved osteoblasts, the in vitro metabolism was reduced consistent with
      noninvolved osteoclasts. The results suggest there may be a primary cellular
      defect and that there appears to be a complex coupling between osteoblast and
      osteoclast function that may lead to sutural synostosis.

PMID- 9145119
TI  - Need for velopharyngeal management following palatoplasty: an outcome analysis of
      syndromic and nonsyndromic patients with Robin sequence.
AB  - The Robin sequence is a pathogenetically and etiologically heterogeneous
      condition that can be a nonsyndromic anomaly or one feature of many syndromes.
      Little information is available regarding the distribution of patients having
      Robin sequence, with or without associated syndromes, who develop velopharyngeal
      dysfunction. In order to discern whether patients with Robin sequence,
      nonsyndromic and/or syndromic, have different velopharyngeal dysfunction rates
      from those observed among all patients undergoing palatoplasty during the same
      time period, a retrospective study was undertaken. The charts of 873 patients
      with overt clefts of the secondary palate managed at a single cleft center
      between 1978 and 1992 were reviewed. Diagnostic criteria for Robin sequence
      included cleft palate without cleft lip, microretrognathia, and perinatal
      respiratory and/or feeding difficulties; 79 such patients (9 percent) were
      identified from the initial group of 873. Of these, 58 patients (7 percent) were
      at least 3 years of age and had sufficient follow-up to allow for evaluation of
      speech outcome by an experienced speech pathologist through a variety of
      methodologies (videonasendoscopy, speech videofluoroscopy, perceptual speech
      characteristics). This group comprised the Robin sequence study population. All
      Robin sequence patients' charts were reviewed by a medical geneticist to confirm
      the presence or absence of a syndrome. Of the original 873 patients, there were
      127 non-Robin sequence patients who were sufficiently cooperative in diagnostic
      testing to yield definitive information. This group comprised the non-Robin
      sequence study population. Among nonsyndromic Robin sequence patients, 15 of 34
      (44 percent) developed velopharyngeal dysfunction and required velopharyngeal
      management, while 2 of 24 syndromic patients (8 percent) developed velopharyngeal
      dysfunction (p = 0.003). Of the 127 non-Robin sequence isolated cleft palate
      patients, 113 were nonsyndromic, of whom 18 percent (20 of 113) required
      velopharyngeal dysfunction management, and 14 were syndromic, of whom 64 percent
      (9 of 14) required velopharyngeal dysfunction management (p = 0.00009). We
      conclude that nonsyndromic Robin sequence patients have a higher rate of
      postpalatoplasty velopharyngeal dysfunction than the nonsyndromic non-Robin
      sequence cleft population. Outcome analysis of velopharyngeal function in cleft
      patients should take into account patients who have cleft palate in association
      with Robin sequence, with or without a recognizable syndrome.

PMID- 9145120
TI  - Fistula formation and repair after palatal closure: an institutional perspective.
AB  - We retrospectively reviewed 119 consecutive patients who underwent cleft palate
      repair at the Mayo Clinic to determine the incidence of postoperative fistula
      formation, to assess possible contributing factors, and to review the methods of
      surgical management. Fistulas of the secondary palate were included, but nasal
      alveolar fistulas and intentionally unrepaired anterior palatal fistulas were
      excluded. Six patients whose repairs were performed after 2.5 years of age were
      excluded to ensure a more uniform patient population. Cleft palate fistulas
      occurred in 13 of the 113 patients (11.5 percent). The median age at repair was
      8.2 months, and the median follow-up period was 5.2 years. Several variables were
      analyzed by means of the log-rank test to determine their significance in
      postoperative fistula formation. Sex, extent of clefting (as estimated by the
      Veau classification), and type of palatal closure did not significantly affect
      the rate of fistula formation. However, patients who had palatal closure at an
      age younger than 12 months had a lower incidence of fistula formation (7.8
      percent) than children whose closures were performed between the ages of 12 and
      25 months (19.4 percent) (p = 0.058). The strongest predictor of the occurrence
      of a cleft palate fistula was the surgeon performing the procedure (p = 0.008).
      Fistula repair was deemed necessary in 11 of 13 patients, and 91 percent of these
      fistulas were healed with a single operation. Most of these fistulas were closed
      by using local flaps and two-layered closures. Cleft palate repair carries a
      significant but acceptable risk of fistula formation, which can be managed with
      local flaps. Fistula occurrence is related most to the experience level of the
      operating surgeon.

PMID- 9145121
TI  - Nicardipine for controlled hypotension during orthognathic surgery.
AB  - Nicardipine is the first intravenously administered dihydropyridine calcium
      channel blocker. Its primary physiologic actions include vasodilatation with
      limited effects on the inotropic and dromotropic function of the myocardium.
      Although it was used in the past as an agent for controlled hypotension during
      orthopedic surgery in adults and children, we are unaware of reports concerning
      its use for controlled hypotension during maxillofacial surgery. We present our
      experience with nicardipine as an agent for controlled hypotension during
      orthognathic surgery in nine adolescents ranging in age from 11 to 16 years and
      in weight from 39 to 61 kg. Following induction of general anesthesia,
      nicardipine was started at 5 micrograms/kg per minute. The target mean arterial
      pressure of 50 to 65 mmHg was reached in 2 to 12 minutes (mean 5.5 minutes).
      Intraoperative infusion requirements to maintain the target mean arterial
      pressure varied from 1 to 7 micrograms/kg per minute (mean 3.6 micrograms/kg per
      minute). No adverse effects related to nicardipine were noted. Our preliminary
      experience suggests the efficacy of nicardipine for controlled hypotension in
      adolescents during orthognathic surgery. Future studies are required to determine
      its advantages and disadvantages over more commonly used agents such as sodium
      nitroprusside or adrenergic antagonists.

PMID- 9145122
TI  - Patterns of facial laceration from blunt trauma.
AB  - The clinical characteristics of craniofacial injuries resulting from various
      modes of blunt trauma, including motor vehicle accidents, falls, and assault,
      have been described extensively in the literature. In this study, specifically
      targeted blunt trauma to selected areas of the face was used to recreate soft
      tissue laceration injuries on 19 cadaver heads. The patterns of laceration
      produced were then examined by location, size, penetrated skin depth, and
      associated muscle and bony involvement. Results showed reproducible patterns of
      lacerations on the forehead, bilateral superior orbital rim, nose, perimaxillary
      region, and chin. Six of 19 cadaver faces were undermined prior to blunt trauma
      to determine the effects of subcutaneous attachments on laceration patterns.
      Results showed no consistent difference in laceration patterns between undermined
      skin and intact skin. Our findings suggest that in response to blunt trauma, the
      skin breaks along selected lines of least resistance that closely parallel
      cleavage lines of the face and that the patterns of laceration generated are
      associated with inherent structural and biomechanical properties of the skin,
      independent of subcutaneous attachments. Blunt trauma lacerations to the face
      therefore may occur in a consistent and reproducible manner and may be subject to
      classification.

PMID- 9145123
TI  - Reconstruction of complex midfacial defects.
AB  - Modern treatment of complex midfacial defects has evolved over the past 5 years,
      primarily with the advent of reliable vascularized bone flaps and osseointegrated
      implants. To determine the effectiveness of these advances, 26 consecutive
      patients with complex midfacial defects treated from 1991 through 1995 with
      immediate muscle-flap coverage were evaluated. The etiology of the defect
      included neoplasm (n = 23) and trauma (n = 3). Seventy-eight percent of the
      patients received adjuvant radiation therapy. Follow-up ranged from 3 months to 4
      years, with a mean of 18 months. Twenty-three patients (88 percent) were
      reconstructed with a single major procedure. All patients had free-flap
      reconstruction, and 100 percent of the flaps survived. Late tumor recurrence was
      seen in 5 of 23 patients (22 percent) and was detected promptly. Aesthetic and
      functional results were rated good or excellent in 77 and 88 percent of the
      patients, respectively, as determined by patient questionnaires and physical
      examinations. Fourteen of 18 patients (78 percent) undergoing partial or complete
      alveolar ridge resection received dental rehabilitation, 43 percent of whom
      received osseointegrated implants into either a bone flap or remaining native
      bone. Osseointegrated implants were inset during the initial reconstruction 50
      percent of the time. A treatment algorithm for free-flap selection based on the
      size of the defect and the bony requirement for reconstruction is presented. Bony
      restoration is only required in those areas where osseointegrated implants need
      to be placed. In such cases, the fibula osteocutaneous free flap is the flap of
      choice. Otherwise, soft-tissue flaps are selected based on wound size. Immediate
      free-flap coverage provides effective, single-stage treatment, both aesthetically
      and functionally, for complex midfacial defects.

PMID- 9145124
TI  - Total face reconstruction with one free flap.
AB  - A bilateral extended scapular (scapular-parascapular) free flap was used in five
      patients with severe facial burn sequelae for complete resurfacing of the face
      with the exception of the nose, which was reconstructed in a separate operative
      procedure. All the flaps survived. Four were utilized for complete face
      resurfacing and one for neck and partial face resurfacing. The results were
      classified subjectively according to both patient and surgeon opinion. Good to
      fair results were obtained. The authors believe that this method might be further
      explored to obtain better results in these difficult cases.

PMID- 9145125
TI  - Cervicoplasty: nonexcisional anterior approach.
AB  - The purpose of this paper is to demonstrate a technique of cevicoplasty by means
      of a submental incision exclusively, without removal of skin. This technique is
      indicated in patients with good-quality skin that has adequate capacity for
      contraction and redraping. The neck is approached by means of a 3- to 4-cm
      incision posterior to the submental crease. A thick subcutaneous flap is
      developed. Initial "open" dissection is continued with dissection using the
      endoscope. All the fat over the platysma muscle is dissected off. The dissection
      follows a triangle outlined by the sternocleidomastoid muscles. An insulated
      suction coagulator is used for hemostasis. Conservative defatting of the
      subcutaneous layer is done, and no suction lipectomy is used routinely. However,
      all the fat pad between the platysma borders and the fat pad between the
      mylohyoid and the digastric muscles are removed. The digastric muscles are either
      "shaved off" or plicated in the midline with 3-0 nylon sutures. This provides a
      smooth and flat contour to the submental area. Subplatysmal dissection beyond the
      submaxillary salivary gland is done with the aid of the endoscope. After a trial
      of advancement, the medial borders of the platysma are resected, and plication in
      the midline is performed from the level of the thyroid cartilage to the symphysis
      of the mandible. In most cases, a backcut on the platysma from the thyroid
      cartilage level in an oblique direction for about 3 to 4 cm is done to avoid
      secondary lateral platysma bands. If no good definition on the submental angle is
      obtained, an interlocked suture suspension with anchoring to the mastoid fascia
      is performed. The relative value of this maneuver will be discussed. The skin is
      allowed to redrape. Usually, after medial advancement of the platysma, an
      additional platysma-skin separation is needed in some segments to allow smooth
      contour on the surface of the skin. The suture suspension may leave minimal
      rippling laterally. This usually disappears in a few days. The technique
      described has been used for several years as an isolated procedure or as a part
      of a full endoscopic face lift without skin excisions. If used in the right
      patient, the result is comparable with that of the open excisional approach and
      has a high rate of satisfaction. The long-term durability remains to be seen.

PMID- 9145126
TI  - The significance of digastric muscle contouring for rejuvenation of the submental
      area of the face.
AB  - The significance of a large, bulky digastric muscle in contributing to an
      objectionable neck contour should be appreciated in aesthetic surgery. Over the
      last several years, patients have achieved improved correction of neck contour
      problems by precise anatomic diagnosis followed by appropriately planned and
      executed repair. The submental contour correction in the past addressed only
      problems of the skin, subcutaneous fat, platysma muscle, subplatysmal fat,
      submaxillary glands, thyroid cartilage, and hyoid bone. Techniques that address
      each of these components can result in excellent rejuvenation of the neck and
      mandibular border. However, on occasion, after application of these conventional
      techniques, a still less than adequate neck contour may result. This results from
      a fullness in the submental region. Careful preoperative and intraoperative
      assessment may reveal the etiology to be a large, bulky anterior belly of the
      digastric muscle. To address this problem, the surgical technique of partial
      resection (tangential excision) of the anterior belly of the digastric muscle is
      performed. To date, this technique has been performed on 21 patients who
      demonstrated an objectionable bulge in the submental region after correction of
      skin, fat, platysma, and submaxillary gland problems. No untoward result or
      complication has been associated with this procedure. The benefits have been a
      pleasing, well-contoured submental area, prevention of residual fullness, ease of
      procedure, and avoidance of the need for secondary neck contouring procedures.

PMID- 9145127
TI  - Modest release of adipsin/factor D by liposuction when using the superwet or
      tumescent technique.
AB  - Human adipsin is recognized to be identical to factor D, which plays an important
      role in activation of the alternative complement pathway. Since adipsin/factor D
      is present in high amounts in adipose tissue, liposuction theoretically could
      result in an increased release of this serine protease into the bloodstream. In
      the present study, adipsin/factor D was measured in 22 patients undergoing
      syringe-assisted liposuction using the superwet or tumescent technique. Despite a
      relatively high mean aspirate volume (2648 ml), only a very modest increase in
      adipsin/factor D concentration was found during liposuction. All values before,
      during, and after liposuction were within the range found in healthy blood
      donors. Furthermore, there was no correlation between adipsin/factor D values and
      C3 activation products. We conclude that liposuction with the present techniques
      results in a very modest release of adipsin/factor D that is not associated with
      increased complement activation.

PMID- 9145128
TI  - Assessment and longevity of the silicone gel breast implant.
AB  - Many patients are now consulting plastic surgeons for evaluation of their
      silicone gel breast implants. This study assesses the accuracy of a clinician's
      ability to determine if a silicone gel breast implant has failed. In addition, it
      sheds light on the long-term integrity of the silicone gel breast implant. This
      study examined the condition of 350 silicone gel breast implants in a group of
      159 of the authors' patients who previously had undergone augmentation
      mammaplasty or breast reconstruction. These women underwent secondary open
      procedures including capsulotomy or capsulectomy for fibrous capsule
      contractures, exchange of implants, or other revisional surgery. The condition of
      the implant was noted at the time of this secondary operation. The preoperative
      evaluation, which included the patient's history and physical examination and
      often mammography, was then matched against the operative findings to determine
      the pertinent factors that predict the integrity of a silicone gel breast
      implant. A history of trauma and/or a reported change in shape of a patient's
      breast correlated with implant failure. An analysis of implant failure as a
      function of implant age revealed that 63 percent of silicone gel breast implants
      in place 12 years or greater in this study population were not intact. A change
      in the patient's physical examination, including a softened breast consistency
      and/or the presence of a nodule or mass adjacent to an implant, also was
      suggestive of implant failure. Several different mammographic presentations of
      implants that were not intact were identified. This modality predicted implant
      failure in 89 percent of implants studied. It is hoped that this information will
      help clinicians to make a more accurate assessment of the condition of a
      patient's silicone gel breast implant. It should be noted that all women in our
      study underwent secondary procedures, as stated above. The results obtained apply
      to this patient group but may not specifically pertain to the general implant
      bearing population.

PMID- 9145129
TI  - Comparison of nipple projection with the modified double-opposing tab and star
      flaps.
AB  - This study compared nipple projection after nipple reconstruction (following
      breast mound reconstruction) with either the modified double-opposing tab flap or
      the star flap. Areolar reconstruction and pigmentation of the nipple were
      achieved with tattooing. Nipple projection for 153 nipples was measured at least
      6 months after the reconstruction, when projection was believed to have become
      stable. Mean follow-up was 2.27 years. In the 106 nipples reconstructed with
      modified double-opposing tab flaps, the mean projection was 2.4292 mm, while in
      the 47 nipples reconstructed with star flaps, the mean projection was 1.9681 mm
      (p = 0.021). We conclude that although both methods are effective, the modified
      double-opposing tab flap has slightly more projection after approximately 2
      years. It is not known, however, whether this is because of reduced flap atrophy
      or longer initial projection by the modified double-opposing tab flap; further
      studies are ongoing.

PMID- 9145130
TI  - Thermal injury to TRAM flaps: a report of five cases.
AB  - Five cases of burns occurring in TRAM flaps utilized for breast reconstruction
      are presented in this study. These injuries resulted from exposure to thermal
      and/or solar radiation. We believe that the physiologic changes that result from
      flap elevation and transposition, mainly denervation, negate the autonomic
      protective mechanisms for heat dissipation. This renders the flaps more
      susceptible to injury from these energy forms. Because of these findings, we urge
      all plastic surgeons who perform TRAM flap reconstructions to carefully instruct
      their patients to avoid exposing their flaps to heat and solar radiation.

PMID- 9145131
TI  - Reduction of progressive burn injury by using a new nonselective endothelin-A and
      endothelin-B receptor antagonist, TAK-044: an experimental study in rats.
AB  - Endothelins are well-known vasoconstrictor peptides produced by vascular
      endothelial cells that have been reported to have a fundamental role in
      regulation of the systemic blood circulation. Plasma levels of endothelins are
      increased by burn injury, which also causes thrombosis and occlusion of vessels
      in the dermis as well as a vascular response in the adjacent uninjured dermis.
      Diminished blood flow leads to progressive ischemia and necrosis of the dermis
      beneath and around the burn (zone of stasis). If blood flow could be restored in
      this zone, secondary tissue damage would be minimized. In this study we examined
      the effects of a new nonselective endothelin receptor antagonist, TAK-044 (Takeda
      Chemical Industries, Ltd., Osaka, Japan), on burn trauma in rats. Fifty male
      Sprague-Dawley rats weighing an average of 450 gm were burned with a brass probe
      that produced a row of three burns 10 x 30 mm in size and two intervening
      unburned areas 5 x 30 mm in size. Rats were divided into five groups of 10
      animals. Four groups received 0.01, 0.1, 1 or 10 mg/kg of TAK-044 via the dorsal
      vein of the penis immediately after burn trauma, while the control group received
      the same volume of saline. Skin blood flow was measured with a laser-Doppler
      flowmeter, and the development of edema and the area of necrotic tissue also were
      determined. Inhibition of endothelin activity by TAK-044 after burn injury
      improved microvascular perfusion in the zone of stasis and prevented the
      progression of tissue damage in this zone. This supports the role of endothelins
      in the progression of burn injury in the zone of stasis. TAK-044 was most
      effective in preventing progressive burn damage at a dose of 1 mg/kg. The extent
      of necrosis and edema was reduced significantly, and blood flow in the zone of
      stasis was increased in the treated rats.

PMID- 9145132
TI  - The effect of hyperbaric oxygen therapy on a burn wound model in human
      volunteers.
AB  - A previous nonblinded study has suggested beneficial effects from hyperbaric
      oxygen treatment of superficial partial-thickness radiation burns in human
      volunteers. This protocol was designed to either confirm or challenge these
      previous findings in a randomized, blinded format. Twelve healthy, nonsmoking
      volunteers (7 males, 5 females) participated. All were screened for
      contraindications to hyperbaric oxygen therapy (acute sinusitis, otitis media,
      pneumonia, pregnancy, active cancer, pneumothorax) and given a single test
      hyperbaric exposure. A standardized wound model was employed for the painless
      creation of a volar forearm lesion on volunteers by applying a suction device to
      form a blister, excising its epidermal roof, and irradiating the exposed dermis
      with ultraviolet light. Subjects were randomized into either a hyperbaric oxygen
      group (100% oxygen at 2.4 ATA, n = 6) or the sea-level air-breathing equivalent
      control group (8.75% oxygen at 2.4 ATA, n = 6). Both groups then underwent
      standard hyperbaric therapy. The subjects, the hyperbaric oxygen chamber
      operators, and the monitoring clinicians were all blinded to the oxygen
      concentration administered. Each subject received two dives per day over a 3-day
      period. The wounds were studied noninvasively prior to treatment and once per day
      over 6 days for size, hyperemia, and exudation, with epithelialization as the
      endpoint. The averages for each measurement of the hyperbaric oxygen group versus
      the control group were computed by means of a one-tail t test; p was considered
      significant at less than 0.05. Daily wound size, hyperemia, and exudation
      measurements were significantly different on day 2. The hyperbaric oxygen group
      showed a 42 percent reduction in wound hyperemia, a 35 percent reduction in the
      size of the lesion, and a 22 percent reduction in wound exudation (p values of
      0.05, 0.03, and 0.04, respectively). No significant difference was noted for
      epithelialization. Observed differences in wound size, hyperemia, and exudation
      were attributable to hyperbaric oxygen therapy. This study further supports
      earlier conclusions that hyperbaric oxygen therapy is beneficial in a superficial
      dermal wound.

PMID- 9145133
TI  - Adventitial stripping does not strip the adventitia.
AB  - This study investigates the process of stripping the adventitia off a blood
      vessel, which is a normal procedure prior to performing a microvascular
      anastomosis. In five rats, the common carotid and the superficial femoral
      arteries of one side were stripped sharply, whereas the arteries of the other
      side were left unstripped to serve as controls. In a further set of five rats,
      the arteries were stripped bluntly. Immediately following stripping, experimental
      and control arterial segments were removed. Histology of cross sections of the
      segments was studied. In no case was there complete removal of the adventitia.
      When stripped and control arterial sections were compared, no significant
      difference between cross-sectional adventitial areas could be demonstrated.
      Morphologic study revealed that stripping mainly removes large collagen fibers
      from the adventitia. The small collagen fibrils that are still in place fan out
      in such a way that although considerable tissue is removed, the volume that the
      adventitia occupies remains the same. Stripping the adventitia does not cause
      complete removal of the adventitia, and in this study no significant reduction in
      the adventitial volume could be found. Stripping does, however, allow a better
      view of the cut edge of the vessel wall under an operating microscope. Since
      blunt stripping could cause damage to other vessel wall layers, sharp stripping
      is to be preferred.

PMID- 9145134
TI  - Intraoperative electroneurodiagnostics (transcranial electrical motor evoked
      potentials) to evaluate the functional status of anterior spinal roots and spinal
      nerves during brachial plexus surgery.
AB  - Intradural spinal root lesions cannot be recognized by dissecting the brachial
      plexus and lead to ineffective surgery if they remain undetected. Therefore,
      patients need to undergo a diagnostic procedure to assess the intradural status
      of the spinal roots. Although motor recovery is the main goal of brachial plexus
      surgery, the techniques currently applied do not permit adequate evaluation of
      the anterior root. In search of an alternative, we performed intraoperative motor
      evoked potentials. Ninety spinal nerves in 19 patients suffering from brachial
      plexus lesions were dissected. Twenty-seven spinal nerves were avulsed; 8 nerves
      were disrupted and 17 were completely scarred, resulting in 25 stumps. Thirty
      eight nerves appeared to be undamaged. On central stimulation, nerve compound
      action potentials were recorded from the exposed spinal nerves. Nerve compound
      action potentials could only be recorded from 21 stumps and from 32 apparently
      undamaged nerves. No recordings were obtained from 4 stumps and 7 spinal nerves
      in continuity. According to these findings, it is highly probable that surgery
      would have been insufficient in 10 spinal nerves if intraoperative motor evoked
      potentials had not been performed. We conclude that (1) intraoperative motor
      evoked potentials are an effective means for investigating the functional status
      of anterior motor roots and motor fibers in exposed spinal nerves, and (2) the
      use of motor evoked potentials should be considered during brachial plexus
      surgery to improve interventions.

PMID- 9145135
TI  - The gracilis myofasciocutaneous flap: vascular anatomy and clinical application.
AB  - Unreliable skin perfusion has been reported frequently in the gracilis
      myocutaneous flap, resulting in moderately high partial flap necrosis. We
      modified the traditional myocutaneous operative technique by including all
      available regional fascia and created a myofasciocutaneous flap with increased
      skin viability. In addition, we defined the arterial anatomy of the flap that
      contributes to enhanced flap survival. In a cadaver study, blue latex was
      injected into the external iliac arteries of 11 cadaveric legs and the gracilis
      myofasciocutaneous flap dissected. Selective ink injection of the pedicle and
      perforating vessels also was performed in 8 legs. Two additional legs were
      injected with a barium-latex mixture, cut into 2-cm-thick transverse sections,
      and radiographed. Dissections demonstrated arterial connections between the
      pedicle vessel (medial femoral circumflex artery) and fasciocutaneous perforating
      vessels from the superficial femoral artery. Perforating vessels contribute to an
      axially oriented fascial network that supplies the overlying skin. Selective ink
      injections demonstrated the individual primary cutaneous vascular territories for
      each perforator. Radiographs of 2-cm-thick transverse sections confirmed the
      presence of arterial connections between the pedicle and the superficial femoral
      artery perforators. Twelve patients, previously pelvically irradiated, then
      underwent harvest of 18 large, longitudinally oriented (8-cm-wide, up to 30-cm
      long) gracilis myofasciocutaneous flaps. All fascia beneath the skin paddle was
      taken in continuity with the deep fascia surrounding the gracilis muscle to
      minimize disturbance of any connecting vasculature held within the fascia.
      Patients were followed for an average of 12.1 months (range 3 to 31 months).
      Minor complications related to the flaps occurred in 6 of 12 patients (50
      percent), i.e., seromas, mild wound infections, and a partial dehiscence;
      however, vascularity was excellent with no partial or complete flap necrosis. All
      wounds healed completely.

PMID- 9145136
TI  - Free composite serratus anterior and rib flaps for tibial composite bone and soft
      tissue defect.
AB  - Open fracture in the lower extremity often involves composite bone and soft
      tissue defects. For patients with extensive segmental bone defects, vascularized
      fibular transfers can be utilized and are generally accepted as one of the best
      options for reconstruction of intercalary defects. In some cases, either
      bilateral tibias and fibulas are fractured or the contralateral fibula is
      traumatically damaged or absent, precluding free fibular transfer. If an
      osteocutaneous fibular flap cannot be used to manage such a defect, a composite
      serratus anterior and rib flap may be considered. Nine composite serratus
      anterior and rib flaps, with or without latissimus dorsi transfers, were
      performed in eight patients between August of 1993 and March of 1994. One patient
      sustained a left knee disarticulation and underwent reconstruction for a right
      tibial defect. He failed to achieve lower extremity function within 2 years and
      was considered a failure. One flap failed, and the patient underwent a below-knee
      amputation. The remaining six patients received seven composite flaps for tibial
      and calcaneal defects and could ambulate without assistance. Based on this
      review, we conclude that the composite serratus anterior and rib flap with
      optional latissimus dorsi muscle can be used for (1) bilateral tibial fibular
      fractures, (2) contralateral lower limb amputation with fillet of the amputated
      leg if the leg is present for harvest, (3) contralateral middle-third fracture of
      the fibula, (4) patients in whom iliac bone is not suitable because of either a
      bone defect greater than 10 to 12 cm or previous harvest of bone graft, and (5)
      extensive composite bone and soft-tissue defects.

PMID- 9145137
TI  - Augmentation of random-flap survival by implantation of vascularized fascia
      allografts and temporary immunosuppression: implications for flap fabrication.
AB  - The purpose of this study was to explore the possible use of an allogeneic
      vascular source for flap fabrication. Epigastric fascia with its superficial
      epigastric vessel pedicle was harvested from the donor rat and microsurgically
      revascularized in the recipient rat across a major histocompatibility barrier.
      ACI rats (Rtl-a) served as donors, and Lewis rats (Rtl-1) served as recipients.
      The recipient rat was immunosuppressed with a daily dose of 2 mg/kg cyclosporin A
      plus 5 mg/kg prednisone for 4 weeks. Three experiments were performed for skin,
      muscle, and bone studies. In experiment 1 (20 Lewis rats), placement of the
      allotransplanted fascia underneath the epigastric skin significantly improved the
      survival of a random epigastric skin flap raised 3 weeks later (7.35 +/- 0.65 cm2
      versus 6.09 +/- 0.90 cm2, p < 0.05). Immunosuppression was discontinued 10 days
      after flap elevation with no observable additional skin necrosis. In experiment 2
      (13 Lewis rats) and experiment 3 (14 Lewis rats), segments of isogeneic muscle
      and bone were grafted successfully on the allotransplanted fascia, respectively.
      The survival of these grafts was confirmed by metabolic bone activity, bone
      labeling, microangiography, and histologic studies and further confirmed 2 weeks
      after cessation of immunosuppression. An allotransplanted fascia as a vascular
      source proved in this model its capability to improve the survival of a random
      skin flap and to accept a free bone or muscle graft with temporary
      immunosuppression. These findings hold promise for possible use of an allogeneic
      vascular source in flap fabrication.

PMID- 9145138
TI  - Imaging of the Apert syndrome hand using three-dimensional CT and MRI.
AB  - Imaging of the Apert syndrome hand is usually done with plain x-rays. This gives
      only a limited assessment of the grossly abnormal anatomy. Computed tomography
      (CT) and magnetic resonance imaging (MRI) have the ability to comprehensively
      demonstrate the spatial arrangement of the bones as well as the anatomy of the
      soft-tissue structures. This paper demonstrates the use of these two imaging
      modalities in the complex Apert syndrome hand to improve surgical planning and
      treatment.

PMID- 9145139
TI  - The Apert syndrome hand: pathologic anatomy and clinical manifestations.
AB  - The Apert syndrome hand demonstrates many typical clinical features including
      syndactyly, symbrachyphalangism, and growth disturbances. This is due to the
      grossly abnormal anatomy of both the skeletal and soft-tissue structures
      associated with a progressive disease process. This paper presents a clinical,
      radiologic, and histologic analysis of the Apert syndrome hand anatomy and
      correlates it with the clinical manifestations. It also links hand and
      craniofacial dysplasia to other regions of the skeleton as well as the overall
      disease process. From our analysis, we conclude that there is a genetic anomaly
      causing variable and uncoordinated differentiation of the mesenchyme at the time
      of embryologic separation into its various skeletal components, particularly in
      the distal limb bud and craniofacial skeleton. This disease process continues
      postnatally in endochondral bone growth center malformation and malfunction as
      well as ectopic cartilage ossification in soft tissues. We discuss the role of
      abnormal musculotendinous anatomy and altered biomechanical forces in relation to
      these processes.

PMID- 9145140
TI  - Optimization of the MGH repair using an algorithm for tenorrhaphy evaluation.
AB  - Previous investigations have demonstrated the superior strength and toughness of
      the MGH four-strand tendon repair technique and shown that it neither weakens
      during maximum tendon softening nor interferes with healing in an in vivo rabbit
      model. In the current study, the biomechanical performance of the modified Becker
      (MGH) and the modified Kessler repairs were compared in situ using a dynamic
      human cadaveric model to evaluate strength, toughness, glide efficiency, and
      operator variability. Three different surgeons performed a total of 42 zone II
      flexor digitorum profundus repairs in 14 fresh human cadaver hands. The modified
      Becker (MGH) repairs were stronger (79 +/- 3 versus 64 +/- 4 N; p < 0.01) and
      tougher (0.092 +/- 0.002 versus 0.078 +/- 0.003 J; p < 0.01) than the Kessler
      repairs while allowing equally efficient glide (32 +/- 6 versus 33 +/- 4 percent;
      p > 0.9). Strength was operator-dependent only for the modified Kessler repair (p
      < 0.005). We then established the optimal configuration of the MGH tenorrhaphy
      (number of preloaded crosses on either side of the tendon transection) by
      examining gap resistance ex vivo. Fifty-one MGH flexor tendon repairs were
      performed on explanted fresh human cadaver tendons. The experimental groups were
      randomly assigned to receive 0, 1, 2, 3, or 4 crosses on each side of the
      tenorrhaphy. Strength and toughness to gap formation and to ultimate failure were
      assessed tensiometrically. The MGH two-cross configuration was most resistant to
      gap formation (peak load 39 +/- 3 N; p < 0.05), establishing this configuration
      as the optimal design of this four-strand crisscrossing repair technique. The
      augmented Becker (MGH) repair is significantly stronger and tougher than the
      modified Kessler repair and demonstrates no operator dependence. It is a superior
      technique for zone II tenorrhaphy in the human hand. An algorithm is presented as
      a systematic approach that includes the important elements necessary for the
      rigorous biomechanical evaluation of any tendon repair technique.

PMID- 9145141
TI  - Classification and reconstructive options in foot plantar skin avulsion injuries.
AB  - Between 1989 and 1994, 28 patients who had plantar avulsion injuries were
      treated. Patient ages averaged 30 years (range 7 to 62 years). Length of follow
      up averaged 20 months. Five patients (18 percent) were classified as having
      suprafascial avulsions, where the shearing plane was limited to the superficial
      subcutaneous layer, leaving the deeper subcutaneous fat. Twenty-three patients
      (82 percent) were classified as having subfascial avulsions, where the stripping
      force extended deep into the plantar aponeurosis. For the suprafascial avulsions,
      defatting these flaps and replacing them with full-thickness skin grafts was the
      treatment of choice. For the subfascial group, the avulsions with proximally
      based flaps (4 patients) that were well nourished by mediolaterally orientated
      neurovascular bundles could be treated by sewing the avulsed flaps tension-free
      back to their former positions. For the subfascial group with distally based
      flaps (19 patients), the avulsed flaps were supplied by anteroposteriorly
      orientated vascular plexuses that were compromised. Primary revascularization of
      the soft tissue should be considered whenever possible. Among them, 10 patients
      attempted microvascular salvage. Only 3 patients succeeded with
      revascularization. In the remaining 16 patients, the avulsed flaps went on to
      partial or complete necrosis, and these required secondary reconstruction with
      free muscle flaps for heel defects.

PMID- 9145142
TI  - A hemodynamic approach to clinical results in the TRAM flap after selective
      delay.
AB  - The delay phenomenon in the transverse rectus abdominis myocutaneous (TRAM) flap
      was studied by means of a laser-Doppler flowmeter and an echo color-flow Doppler
      device. Twenty-eight patients who underwent breast reconstruction with a TRAM
      flap in our hospitals were analyzed. Eighteen of them underwent selective delay 1
      month before the major surgical procedure, and of them, 15 completed the
      reconstructive procedure. Ten patients were used as a control group and underwent
      TRAM flap breast reconstruction without selective delay. Cutaneous blood flow in
      the TRAM flaps was measured in 20 patients with a laser-Doppler flowmeter, and
      measurements were taken before, during, and after the surgical procedure,
      following a standardized protocol, as in Tuominen's original scheme. Variations
      in the cutaneous blood flow in the standard TRAM flap (10 patients) confirmed
      data obtained from the literature, i.e., an increase when elevating the cutaneous
      and subcutaneous parts of the flap and a decrease when ligating the deep inferior
      and superficial epigastric vessels. Compared with the standard TRAM flap, blood
      flow in the delayed flaps (10 patients) seemed to be more stable, without falling
      under the baseline. When elevating the cutaneous and subcutaneous parts of the
      flap (phase 3), blood flow values reached 120.2 percent (SEM 46.8 percent) on the
      random side and 131.6 percent (p < 0.009, SEM 9.58 percent, standard deviation
      30.3 percent) on the axial side. During phase 4 (cutting the rectus muscles),
      blood flow values reached 115.0 percent (SEM 40.5 percent) on the random side and
      102.8 percent (SEM 1.2 percent, standard deviation 3.8 percent, p < 0.049) on the
      axial side. In order to obtain further hemodynamic data, 10 patients who
      underwent selective vascular delay 1 month prior to breast reconstruction with a
      delayed TRAM flap in our hospitals were then studied by means of an echo color
      flow Doppler device. Two of these patients also had been studied with the laser
      Doppler flowmeter. Superior epigastric artery diameter (in millimeters) and
      resistivity (expressed as Pourcelot's index) were measured before and after
      selective delay of the deep and superficial inferior epigastric vessels,
      following a standardized protocol. Measurements were taken with 7.5- and 10-MHz
      linear probes at a point located after the origin of the costomarginal artery. In
      every patient an increase in the superior epigastric artery diameter and a
      decrease in the resistivity index were observed, and this was statistically
      significant. In the nonirradiated patients, the increase in the average diameter
      of the superior epigastric artery was 98.1 percent, and the average resistivity
      index decrease was 14.1 percent. In the irradiated patients, the increase in the
      average diameter of the superior epigastric artery was 35.5 percent, and the
      average resistivity index decrease was 29.8 percent. In conclusion, laser-Doppler
      flowmeter evaluations show that cutaneous blood flow in the delayed flap is more
      constant and undergoes fewer variations than that in the standard TRAM flap. In
      addition, echo color-flow Doppler indicates that the basis for the increase in
      the vascular territory of the superior epigastric artery caused by the delay
      maneuver is an increase in the superior epigastric artery diameter, always
      accompanied by a decrease in the resistivity index. Two different mechanisms seem
      to us to be related to these modifications in the blood circulation. In the
      nonirradiated patients, superior epigastric artery dilation prevails, whereas in
      the irradiated patients, a decrease in the resistivity index is the dominant
      mechanism of compensation. These hemodynamic findings well support the decrease
      in flap necrosis reported in our series (standard TRAM: 30 percent; delayed TRAM:
      7.1 percent).

PMID- 9145143
TI  - Profiling the physician.

PMID- 9145144
TI  - MRI interaction with tattoo pigments: case report, pathophysiology, and
      management.
AB  - A case is reported in which the presence of a decorative tattoo resulted in pain
      and termination of an MRI study. The ferromagnetic nature of the tattoo and iron
      oxide tattoo pigments is demonstrated. The pathophysiology of tattoo/MRI
      interaction is discussed, as is an approach to the prevention and treatment of
      this complication.

PMID- 9145145
TI  - Long-term outcome of extensive skull reconstruction using demineralized
      perforated bone in Siamese twins joined at the skull vertex.
AB  - The successful use of cortical demineralized perforated bone in the treatment of
      extensive skeletal defects in children is exemplified by this case involving
      Siamese twins joined at the skull vertex. Four years following extensive skull
      reconstruction using demineralized perforated bone, an examination revealed
      successful calvarial reconstruction in one twin. The other twin required
      additional implants of demineralized perforated bone to fill in defects. However,
      a histologic examination taken following this additional procedure revealed that
      these implants neither caused tissue reaction over a 4-year period, nor showed
      signs of resorption. Bony remodeling and new bone formation were in progress.
      Compared with other bone substitutes, demineralized perforated bone has proven to
      be effective in the treatment of large skull defects in children.

PMID- 9145146
TI  - The reversed-flow temporoparietal fascial flap.
AB  - A patient is reported whose forehead soft-tissue defect was reconstructed by a
      reversed-flow temporoparietal fascial flap. This procedure can shorten the
      operating time. The blood circulation of the flap is satisfactory. The only
      drawback is the resulting scar of the skin-grafted area.

PMID- 9145147
TI  - Functional reconstruction of the upper eyelid after excision of squamous cell
      carcinoma in xeroderma pigmentosum.
AB  - This paper describes a technique for excision of a squamous cell carcinoma of the
      upper eyelid and subsequent functional reconstruction of the lid in a patient
      with xeroderma pigmentosum. By applying the modified technique of temporalis
      muscle flap, the upper eyelid was reconstructed by a skin graft from non-sun
      exposed skin and a muscle pocket of the temporalis muscle. For the mucosal layer
      of the upper eyelid, a transplant of oral mucosa was used. An effective
      functional and aesthetic outcome has been achieved by this technique.

PMID- 9145148
TI  - Breast implant rupture following contralateral mammography.

PMID- 9145149
TI  - Reconstruction of scleroderma of the breast.
AB  - Although limited to a single case, our study suggests that patients with
      localized scleroderma of the breast can incur developmental impairment leading to
      severe breast deformity. The results of any of several methods of breast
      reconstruction were not available to us for review because of the rarity of this
      clinical problem. Tissue expansion allowed our patient to avoid the additional
      scarring and possible functional loss associated with the transfer of autologous
      tissues. Its successful completion in this one patient indicates that it can be
      considered for other patients encountered with similar unusual findings.

PMID- 9145150
TI  - Pedicled latissimus dorsi transfer for immediate soft-tissue coverage and elbow
      flexion.
AB  - This case report describes a new method of unipolar transfer of the latissimus
      dorsi for restoration of elbow flexion. The advantages of the technique are that
      it has superior resting tension compared to other unipolar transfers and provides
      more extensive soft-tissue coverage at the elbow than other unipolar or bipolar
      transfers. The disadvantage is that it does not restore the supinator function of
      the biceps. The technique is felt suitable for traumatic defects requiring
      extensive soft-tissue coverage as well as restoration of an active elbow flexor.

PMID- 9145151
TI  - Reconstruction of the external auditory canal with a laterocervical twisted flap
      (snail flap)
AB  - A case of circumferential reconstruction of the external auditory canal following
      basal cell carcinoma is described using a laterocervical tubed flap. One-stage
      reconstruction with a single flap, absence of donor-site deformity, and easy
      dissection are the main advantages of the procedure, which also can be
      conveniently used to reconstruct part of the concha and the tragal region.

PMID- 9145152
TI  - Immediate reconstruction of the central segment of the mandible using the
      masseter osteomuscular flap.
AB  - We describe a new technique for reconstruction of the central segment of the
      mandible using a masseter osteomuscular flap. The advantages of this method are
      that bone viability is preserved, both form and function of the mandible are
      maintained, it is a local flap with low donor-site morbidity, and the operative
      time is shortened.

PMID- 9145153
TI  - An alternative to arch-bar maxillomandibular fixation.
AB  - This report details a pilot study of the maxillomandibular fixation screw. A
      longer study with a greater number of patients will allow for better evaluation
      of this technique.

PMID- 9145154
TI  - Minimally invasive iliac cancellous bone graft harvesting.
AB  - We have described a technique for harvesting cancellous bone from the ilium that
      is minimally invasive and safe. This technique results in minimal donor-site
      morbidity, is quick and easy to perform without the need for special equipment or
      instruments, and allows a two-team operative approach. Sufficient bone graft
      material can be obtained for wide or bilateral clefts. We now use this technique
      routinely to harvest cancellous bone for secondary alveolar bone grafting in
      children with clefts. The procedure could be used in adults, it could also be
      used to obtain bone graft for treating other conditions, and other donor sites
      could be approached with the same technique.

PMID- 9145155
TI  - Arterialized venous flaps from the thenar and hypothenar regions for repairing
      finger pulp tissue losses.
AB  - Pulp tissue loss of the fingers was repaired with arterialized venous flaps from
      the thenar or hypothenar regions in 13 patients. Thirteen of the 15 flaps
      transferred survived completely. The thenar and hypothenar skin is durable and of
      appropriate texture for replacement of finger pulp defects. An average flap size
      of 2 x 3 cm was adequate for repairing the tissue loss of the fingers. These are
      not sensory flaps. However, they exhibited useful sensory recovery within 6
      months of the operation. This method is simple and results in minimal donor-site
      morbidity. The arterialized venous flap is thus a useful alternative for the
      repair of finger pulp tissue losses.

PMID- 9145156
TI  - The venocutaneous fistula: a new technique for reducing venous congestion in
      replanted fingertips.
AB  - The venocutaneous fistula technique, which involves the construction of a
      temporary venous return bypass using a venous graft, was devised to prevent
      venous congestion after fingertip replantation surgery. The proximal side of the
      venous graft is anastomosed to a vein at the dorsum of the finger. The distal
      side of the graft is sutured to the skin around a punch wound on the volar side
      of the replanted fingertip. This procedure was applied successfully to four
      fingertips in two patients without any anastomosis of the proper vein or the
      application of bleeding wound techniques or medicinal leeches. This method
      provides an excellent alternative in the treatment of venous congestion.

PMID- 9145157
TI  - Plastic surgical techniques in the fifteenth century by Serafeddin Sabuncuoglu.
AB  - Serafeddin Sabuncuoglu (A.D. 1385-1468) is the author of the first illustrated
      surgical textbook in the Turkish-Islamic literature, namely, Cerrahiyet-ul
      Haniyye (Imperial Surgery). A pioneer in all fields of surgery. Sabuncuoglu
      developed numerous original techniques. He was a keen observer and inventor and a
      prolific writer who combined his fortune with knowledge of his era. He described
      a mass reduction procedure for the management of gynecomastia, probably one of
      the first attempts at reduction mammaplasty. He gave detailed descriptions of
      different eyelid pathologies and their surgical managements. The aim of this
      study is to investigate the contributions of this remarkable pioneer to the field
      of plastic surgery.

PMID- 9145159
TI  - Misleading codes.

PMID- 9145158
TI  - The vermilion paradox.

PMID- 9145161
TI  - Reducing the pain of suture removal.

PMID- 9145160
TI  - The absence of esophageal lesions in maternal progeny of silicone-injected rats.

PMID- 9145162
TI  - A simple postoperative stent dressing after nipple-areola reconstruction.

PMID- 9145163
TI  - Share your knowledge, transform a life.

PMID- 9145164
TI  - Antibiotic administration.

PMID- 9145165
TI  - Stereotactic biopsy procedures for brain tumor diagnosis.
AB  - Stereotactic biopsy procedures, in which a computer-based, three-dimensional
      image-guided system accurately locates patients' brain tumors, are relatively new
      diagnostic methods. Complications from stereotactic biopsy procedures are minimal
      compared with open craniotomy procedures because they are performed with local
      anesthesia. Perioperative nurses should have knowledge of and be trained in
      stereotactic biopsy procedures to ensure optimal care for patients undergoing
      these procedures.

PMID- 9145166
TI  - Stereotactic pallidotomy for treatment of Parkinson's disease.
AB  - There has been a resurgence of interest in surgical treatment of Parkinson's
      disease in the past five years due to the large number of patients who have
      medically intractable symptoms and because significant improvements in
      neuroimaging and stereotactic techniques have made surgical procedures safer and
      more accurate. Stereotactic pallidotomy procedures allow neurosurgeons to destroy
      a portion of the globus pallidus, and thereby, decrease patients' muscle rigidity
      from Parkinson's disease. These surgical procedures primarily involve magnetic
      resonance-guided stereotactic targeting and microelectrode recording techniques.
      To ensure successful patient outcomes, stereotactic pallidotomy procedures
      require special perioperative nursing interventions discussed in this article.

PMID- 9145167
TI  - The nurse's role in bioethics.
AB  - Hospital ethics committees consist of representatives from multiple disciplines
      who discuss potential issues and real-life ethical dilemmas that confront
      patients, their family members, and the health care professionals involved in
      patient care. Bioethical issues may provoke strong emotional responses from
      ethics committee members. Recognizing the difficulty of resolving issues that
      address moral beliefs is imperative. Nurses are in key positions to help health
      care professionals navigate these troublesome ethical waters.

PMID- 9145168
TI  - Total shoulder arthroplasty.
AB  - Surgeons perform total shoulder arthroplasty (TSA) procedures to reduce patients'
      intractable arthritic pain and to repair humeral head fractures. Total shoulder
      arthroplasty has undergone remarkable advances--not only in prosthetic
      improvements and refinements--but in patient outcomes. Advantages to TSA
      procedures include decreased pain and patients' increased ability to perform
      activities of daily living.

PMID- 9145169
TI  - Patient risk factors for pressure ulcers during cardiac surgery.
AB  - Patients undergoing cardiac surgery have increased risks for developing pressure
      ulcers. The researchers conducted this study to identify preoperative,
      intraoperative, and postoperative factors associated with the development of
      pressure ulcers among patients undergoing cardiac surgery at the Cleveland Clinic
      Foundation. The significant factors associated with pressure ulcer development in
      the study patients were presence of diabetes mellitus and other significant
      comorbid conditions; low preoperative Braden Risk Assessment Scale scores; lower
      preoperative hemoglobin, hematocrit, and serum albumin levels; presence of
      intraaortic balloon pumps in the postoperative period; being turned less often;
      and more rapid returns to preoperative body temperatures. By incorporating
      vigilant observation and timely nursing interventions throughout patients'
      surgical experiences, perioperative nurses can help prevent the development of
      pressure ulcers and promote optimal patient outcomes.

PMID- 9145170
TI  - A statistical method for predicting postanesthesia care unit staffing needs.
AB  - When predicting staffing requirements for postanesthesia care units (PACUs),
      nurse managers are expected to satisfy standards, meet patient care needs, staff
      PACUs to accommodate surgeons' and facilities' needs, and contain costs. The
      authors present a statistical method that offers reliability and accuracy in
      forecasting future patient numbers and related PACU staffing requirements. Nurse
      managers can use this method to decide how frequently they will satisfy staffing
      standards, how many shifts of RNs to schedule each day, and how many months in
      the future to schedule staff members. Future peak numbers of patients for each
      daily shift are based on previous daily peak numbers of patients, and staffing
      requirements can be planned from these predicted peak numbers of patients, using
      a facility's PACU staffing standards.

PMID- 9145172
TI  - Chronic alcohol abuse in elderly surgical patients.

PMID- 9145171
TI  - Calcium phosphate bone cement--the Norian skeletal repair system in orthopedic
      surgery.

PMID- 9145173
TI  - Types of legal claims brought against perioperative nurses.

PMID- 9145174
TI  - Health care reform--the consolation prize.

PMID- 9145176
TI  - Gastroenteritis in Australia: who, what, where, and how much?

PMID- 9145175
TI  - Ten questions that will get you through any research report.

PMID- 9145177
TI  - Low-grade non-Hodgkin's lymphoma--biology and therapeutic approaches.

PMID- 9145178
TI  - Video assisted thoracoscopic surgery (VATS) in Asia--its impact and implications.
AB  - BACKGROUND: Within a short period of time, video assisted thoracoscopic surgery
      (VATS) has revolutionised the practice of thoracic surgery. Most of the existing
      literature, however, is concentrated on the technical aspects. AIMS: We examined
      the impact of VATS on our practice and its implications. METHODS: We reviewed our
      thoracic case load two years before and two years after the introduction of VATS
      in our hospital. RESULTS: We have witnessed a rapid and progressive increase in
      our thoracic case load since the introduction of VATS. With increased experience,
      proportionally more cases were performed using VATS compared to conventional
      surgical access. The increased case load covered a wide range of thoracic
      diseases with the majority for spontaneous pneumothorax and pleural diseases.
      CONCLUSIONS: The higher case load is due to increased referrals which at least
      partly reflect earlier acceptance by both the patients and their physicians for
      surgical intervention. The changing indications for surgery and the high cost
      associated with VATS, however, could place extra demand on the healthcare,
      especially for some countries in Asia. Cost containment is therefore a high
      priority here. More research is greatly needed in this area.

PMID- 9145179
TI  - An analysis of the outcomes of treatment of small cell lung cancer in the
      elderly.
AB  - BACKGROUND: Many cases of small cell lung cancer will occur in the elderly
      population but optimal management of the disease in this age group remains
      uncertain. AIMS: To evaluate treatment of small cell lung cancer in the elderly
      in Australia and to compare treatment received and outcomes with those of younger
      patients. To draw insights from these observations into the optimal management of
      small cell lung cancer in the elderly. METHODS: A retrospective review of
      treatment charts and case notes for 51 elderly patients and 102 younger patients
      was undertaken. RESULTS: Elderly patients had similar baseline parameters with
      respect to disease stage and performance status. Elderly patients were mostly
      treated uniformly with combination chemotherapy, but suffered more dose
      reductions than younger patients. Benefits of chemotherapy were seen even in
      patients with poor performance status. Despite the dose reductions, response
      rates and survival times for elderly patients were usually similar to younger
      patients. CONCLUSIONS: Combination chemotherapy is beneficial to elderly patients
      with small cell lung cancer. Optimal therapy for the elderly may be different
      from that for younger patients and should be defined through prospective
      randomised clinical trials.

PMID- 9145180
TI  - Prevalence of IgE-mediated allergy to latex in hospital nursing staff.
AB  - BACKGROUND: IgE-mediated hypersensitivity to latex proteins has become a
      significant clinical problem over the last decade. Nursing and medical staff are
      at risk because of their occupational exposure to latex. AIMS: To determine the
      prevalence of type I hypersensitivity to latex allergens in the nursing staff of
      an Australian hospital. METHODS: A questionnaire which asked about symptoms
      associated with the use of latex gloves was completed by 140 nurses working in
      the Alfred Hospital (72 in general medical wards, 68 in intensive care units).
      Skin prick tests with eluates of five different types of latex glove as well as
      common aeroallergens (rye pollen and house dust mite) and banana extract were
      performed. RESULTS: Thirty-one nurses (22%) were skin prick test positive to at
      least one of the five latex glove eluates. All of these nurses were atopic,
      having positive skin prick tests to rye pollen or house dust mite. Symptoms of
      local dryness, itch and erythema associated with glove use were reported by more
      than half the study group, but not more frequently by those who were skin prick
      test positive to latex. Urticaria associated with glove use was reported more
      frequently by those with positive latex skin prick tests (13% vs 4%, p = 0.05).
      Eighty-seven per cent of the nurses who were latex skin test positive were also
      positive to banana extract. CONCLUSIONS: IgE-mediated hypersensitivity to latex
      is common in nurses working in an Australian hospital. Glove associated symptoms
      were frequently reported, but in most cases the symptoms were more typical of
      irritant or contact dermatitis rather than type I hypersensitivity reactions.
      However, the extent of subclinical sensitisation to latex found in this study
      suggests that symptomatic latex allergy is likely to emerge as an increasing
      problem for nursing staff in this country.

PMID- 9145181
TI  - Lymphocytopenia in a hospital population--what does it signify?
AB  - BACKGROUND: Lymphocytopenia is a common finding in hospital patients especially
      since the advent of automated differential leukocyte counters. The causes and
      significance of lymphocytopenia are generally poorly understood. There has been
      no large-scale study of its significance for 25 years. The HIV epidemic, and the
      recently described idiopathic CD4+ T-lymphocytopenia have raised interest in this
      finding. AIMS: To describe the spectrum of lymphocytopenia in an adult teaching
      hospital and investigate its clinical significance. METHODS: Using the available
      computer facilities, patients with significant lymphocytopenia (< 0.6 x 10(9)/L)
      were identified over a 102 day period and diagnoses, operations and medication
      lists obtained. Where necessary, patient histories were examined to supplement
      the above information. If feasible, previous and subsequent lymphocyte counts
      were checked to establish if the lymphocytopenia were temporary or longstanding.
      RESULTS: One thousand and forty-two patients were identified, with a mean age of
      59.6 years, of whom 563 were male, and 757 were inpatients. Thirty-six patients
      were pancytopenic. We checked previous and subsequent counts for 698 patients and
      found 45 patients who were consistently lymphocytopenic, some for more than ten
      years. Thirty-four patients with previously normal counts remained
      lymphocytopenic throughout follow up, while 457 had at least one subsequent
      lymphocyte count > 1 x 10(9)/L. We found only one patient who was suspected of
      having idiopathic CD4+ T-lymphocytopenia. Patients fell into several categories
      (with some overlap): bacterial/fungal sepsis (250), post-operative (228),
      corticosteroid therapy (definite 159, suspected 53, inhaled steroids alone 14),
      malignancy (174 definite, six probable), cytotoxic therapy and/or radiotherapy
      (90), trauma or haemorrhage (86), transplants (73-38 renal and 35 bone marrow),
      'viral infections' (26) and HIV infection (13). Thirty-four patients died within
      the study period. CONCLUSIONS: Lymphocytopenia in hospital patients is most
      frequently reversible, and due to acute illness, notably sepsis and trauma
      (including surgery). Malignancy, with or without chemotherapy, and steroid use
      are also common causes, but HIV infection is a relatively uncommon cause in our
      hospital.

PMID- 9145182
TI  - The use of biologics in the treatment of rheumatoid arthritis (RA)--the good news
      and the bad news.

PMID- 9145183
TI  - Alcohol and survival in the elderly: the Dubbo Study.

PMID- 9145184
TI  - Rhabdomyolysis after lung transplantation.

PMID- 9145185
TI  - Health departments--pro and con.

PMID- 9145186
TI  - Health departments--pro and con.

PMID- 9145187
TI  - Danazol in the treatment of a systemic lupus erythematosus (SLE)-like illness
      associated with deficiency of the fourth component of complement.

PMID- 9145188
TI  - Imipenem induced dental staining.

PMID- 9145189
TI  - The significance and distinct interactions of various growth factors in
      physiologic and pathologic megakaryocytopoiesis/thrombocytopoiesis.

PMID- 9145190
TI  - Thrombolytic therapy in patients presenting to a peripheral metropolitan
      emergency department with acute myocardial infarction.

PMID- 9145191
TI  - Mitral-aortic intervalvular fibrosa pseudoaneurysm complicating aortic valve
      endocarditis.

PMID- 9145192
TI  - Rhabdomyolysis and akinetic hyperthermic crisis complicating Parkinson's disease.

PMID- 9145193
TI  - Enhanced gentamicin clearance associated with ileostomy fluid loss.

PMID- 9145194
TI  - It is possible to use clozapine to treat Parkinson's disease.

PMID- 9145195
TI  - Spur cell anaemia resolves after orthotopic liver transplantation (OLT)

PMID- 9145196
TI  - (A)typical Cogan's syndrome.

PMID- 9145197
TI  - Adrenal carcinoma presenting as Conn's syndrome.

PMID- 9145198
TI  - Improved separation and determination of phospholipids in animal tissues
      employing solid phase extraction.
AB  - Separation of five glycerophospholipids having different polar groups,
      phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS),
      phosphatidylglycerol (PG) and cardiolipin (CL), was investigated by means of
      solid-phase extraction (SPE) cartridges. First, the phospholipids were retained
      in an aminopropyl-bonded phase (NH2) cartridge and subsequently eluted as neutral
      (PC and PE) and acidic (PS, PG and CL) glycerophospholipid fractions. Secondly, a
      combination of silica gel (SI) cartridge and NH2 cartridge was employed to
      separate five glycerophospholipids. The polarity of the eluent was responsible
      for neutral glycerophospholipid separation. Concerning acidic
      glycerophospholipids, the separation of PG and CL from PS depended mainly on the
      pH of the eluents, and the separation of PG and CL was affected by the solvent,
      depending on eluent polarities. Favorable recovery (not less than 95%, for five
      authentic phospholipids, 10-100 micrograms each) and repeatability (sigma = 2.3
      for 10 micrograms ranges) were attained by the present method. This method of
      separation was applicable to the analysis of phospholipids in biological samples.

PMID- 9145199
TI  - Protective effects of hydroxybenzoic acids and their esters on cell damage
      induced by hydroxyl radicals and hydrogen peroxides.
AB  - The purpose of this study was to evaluate the hydroxyl radical scavenging
      activities of hydroxybenzoic acids and their esters from both chemical and
      biological aspects. These activities of hydroxybenzoic acids and their related
      compounds were estimated by ESR-spin trapping method, in which 3,4,5
      trihydroxybenzoic acid and its ethyl and propyl esters showed the highest
      activities as estimated by IC50 value (50% inhibition concentration of hydroxyl
      radicals generated in the system): 78.04 +/- 11.23, 95.95 +/- 2.64, and 86.46 +/-
      2.31 microM, respectively. In addition, 3,4,5-trihydroxybenzoic acid (gallic
      acid) at a concentration of 25 microM, protected against dermal fibroblast cell
      damage induced by H2O2, and enhanced the survival to 83.8 +/- 3.1%, in which the
      survival of control was 44.2 +/- 1.0%. Based on these results, the pretreatment
      effects of 3,4,5-trihydroxybenzoic acid n-alkyl esters on cell damage induced by
      H2O2 were examined. The survival of fibroblasts pretreated with the esters
      increased depending on the alkyl chain-length. Both C12 and C16 alkyl esters gave
      almost complete cell survival of 89.5 +/- 2.0% and 91.3 +/- 1.0%, respectively.
      The order of the protective effects of the compounds was in good agreement with
      that of their partition coefficients, suggesting that 3,4,5-trihydroxybenzoic
      acid alkyl esters are incorporated into fibroblasts, and thus prevent the cells
      from the toxicity caused by H2O2. In addition, an increase of intracellular
      peroxide formation in fibroblasts induced by UVA-irradiation, was suppressed to
      2.27 +/- 0.41 nmol/10(4) cells by pretreatment with C16 alkyl ester at a
      concentration of 25 microM. Since 3,4,5-trihydroxybenzoic group has been
      demonstrated to possess a potent scavenging activity of hydroxyl radicals, this
      moiety was indicated to be important in preventing cell damage induced by UVA or
      H2O2: in turn, these produce hydroxyl radicals in the presence of trace metal
      ions such as iron and copper in cells.

PMID- 9145200
TI  - Fluorescence polarization immunoassay of progesterone.
AB  - A homogeneous fluorescence polarization immunoassay (FPIA) was developed to
      measure levels of progesterone in urine using a TDx analyzer in photocheck mode
      (Abbott Labs). Two tracers of ethylenediamine fluorescein thiocarbamyl (EDF) were
      employed; one was synthesized from 11 alpha-hydroxyhemisuccinate progesterone
      (Prog-11OH-HS) and the other was synthesized from 3-(o-carboxymethyl)oxime
      progesterone (Prog-3CMO). Each derivative of progesterone was conjugated with
      bovine serum albumin and used as an immunogen which produced monoclonal antibody
      clone 15A (MAb 15A, anti-Prog-11OH-HS) and clone 2B7 (MAb 2B7, anti-Prog-3CMO),
      respectively. Different combinations of tracers and antibodies were investigated
      in the FPIA system. Similar sensitivity was observed when using the pair, MAb 2B7
      and its homologous tracer, Prog-3CMO-EDF, or MAb 15A and its homologous tracer,
      Prog-11OH-HS-EDF. In this immunoassay, no separation step was required and the
      total time for an assay of 10 samples was approximately 7 min. The progesterone
      detection limit in a 10 microliters sample was 3 ng/ml. The cross-reactivity
      results indicate that the A-, B- and D-ring of a steroid are buried in the
      binding pocket of MAb 15A, while the C-ring faced outward, resulting in cross
      reactivity with 11-alpha hydroxy progesterone. The A-, B- and C-ring of a steroid
      of MAb 2B7, in contrast, are buried deep in the pocket leaving the D-ring facing
      outward, resulting in some different degrees of cross-reactivity with C17
      position substituted steroids.

PMID- 9145201
TI  - Effect of gemfibrozil on centrifugal behavior of rat peroxisomes and activities
      of peroxisomal enzymes involved in lipid metabolism.
AB  - The effect of gemfibrozil, and analogue of clofibric acid, on the centrifugal
      behavior of peroxisomes and activity of peroxisomal enzymes involved in lipid
      metabolism was studied. Rats were fed chow containing 0.2% gemfibrozil for 2
      weeks. Nycodenz gradient centrifugation of the light mitochondrial fraction
      revealed that peroxisomes of gemfibrozil-treated rats were concentrated in
      fractions of higher density compared with control rats. The activity of fatty
      acyl-CoA oxidase, crotonase, beta-hydroxybutyryl-CoA dehydrogenase, and thiolase
      (individual enzymes of the peroxisomal fatty acid beta-oxidation system) were
      enhanced 9.6, 2.3, 3.4 and 9.1 times respectively compared with controls, by
      treatment. The hydroxymethylglutaryl-CoA (HMG-CoA) reductase (rate-limiting
      enzyme of cholesterol synthesis) activity of peroxisomes and microsomes was
      greatly increased by in vivo treatment with gemfibrozil, but was decreased by
      addition of the agent to the assay mixture of the enzyme. Gemfibrozil directly
      inhibited the reductase activity and did so at a lower concentration than
      clofibric acid. Peroxisomal reductase was more resistant to damage by the agent
      than the microsomal enzyme. The HMG-CoA reductase activity of peroxisomes and
      microsomes of hyperlipidemic rats was also increased by in vivo treatment with
      gemfibrozil, whereas the serum cholesterol level was hardly changed. These
      results indicate that the effect of gemfibrozil differs from that of clofibric
      acid, the main difference being the effect on HMG-CoA reductase. Gemfibrozil
      increased reductase activity in vivo, unlike clofibric acid, but inhibited the
      enzyme in vitro to a greater extent than clofibric acid.

PMID- 9145202
TI  - Delayed release of prostaglandins from arachidonic acid and kinetic changes in
      prostaglandin H synthase activity on the induction of prostaglandin H synthase-2
      after lipopolysaccharide-treatment of RAW264.7 macrophage-like cells.
AB  - In a mouse macrophage-like cell line, RAW264.7, arachidonic acid was cleaved
      within 30 min of lipopolysaccharide (LPS)-treatment. However, prostaglandin (PG)
      synthesis did not accompany this cleavage, being delayed by 4 h, although
      significant PGH synthase (PGHS) activity was detected in the lysate of LPS
      nontreated cells. The K(m) value of this basal PGHS activity toward arachidonic
      acid was more than one hundred-fold higher than that for the lysate of cells
      treated with LPS for 4 h. Changes in the sensitivity of the PGHS activity to
      nonsteroidal antinflammatory drugs after LPS-treatment also suggested induction
      of PGHS with different properties from that in the case of basal PGHS. The
      concomitant increase in PGH synthase (PGHS) activity with the induction of PGHS-2
      protein after LPS-treatment suggested a contribution by PGHS-2 to the delayed
      synthesis of PGs in LPS-treated macrophage cells. As for PGHS in the control
      cells without LPS-treatment, a different K(m) value from that of PGHS-1 and the
      lack of cross-reactivity to anti-PGHS-1 antibodies suggested that this basal PGHS
      was different from the typical PGHS-1. The lower affinity of this enzyme for
      arachidonic acid might be the reason for the failure to release PGs by the cells
      without LPS-treatment.

PMID- 9145203
TI  - Decrease in expression of the master operon of flagellin synthesis in a dnaA46
      mutant of Escherichia coli.
AB  - We examined the expression of the fliC, fliA and fihD genes in the dnaA46 mutant.
      In Northern blot analysis, the amounts of fliC, fliA, and flhD mRNA decreased in
      the dnaA46 mutant growing at 37 degrees C but not at 28 degrees C. The promoter
      activity of each gene also decreased in this mutant at 37 degrees C. The decrease
      in expression of the flh D gene was not related to the cAMP-catabolite activator
      protein (CAP) pathway. We tentatively conclude that DnaA protein is involved in
      the expression of the flhD gene by a mechanism independent of the cAMP-CAP
      pathway.

PMID- 9145205
TI  - Effects of mitragynine on cAMP formation mediated by delta-opiate receptors in
      NG108-15 cells.
AB  - Mitragynine, a major constituent of the young leaves of Mitragyna speciosa
      KORTH., has been reported to exert antinociceptive activity in mice. To determine
      the mechanism the influence of mitragynine on cAMP content was measured in NG108
      15 cells which possess delta opioid receptors and alpha 2B-adrenoceptors.
      Mitragynine inhibited the forskolin-stimulated cAMP content in a concentration
      dependent manner as well as morphine and noradrenaline. Mitragynine- and morphine
      induced inhibition of cAMP content were blocked by naloxone. Although idazoxane
      inhibited noradrenaline-induced inhibition of the cAMP content, idazoxane had no
      effect on mitragynine-induced inhibition. These results suggest that mitragynine
      acts directly on opioid receptors, but not on alpha 2-adrenoceptors, to show
      antinociceptive activity.

PMID- 9145204
TI  - Participation of leukotriene D4 and tumor necrosis factor on lipopolysaccharide
      induced airway hyperresponsiveness in guinea pigs.
AB  - In guinea pigs, a marked increase in airway responsiveness to acetylcholine (Ach)
      was observed at 2 h after lipopolysaccharide (LPS) inhalation. To examine the
      mediators responsible for the airway hyperresponsiveness, the changes of peptide
      leukotrienes (LTs), tumor necrosis factor (TNF), interleukin-1 (IL-1), histamine
      and 5-hydroxytryptamine (5-HT) levels in bronchoalveolar lavage fluid (BALF) were
      measured. Airway responsiveness to Ach reached a peak 2 h after LPS inhalation.
      The influx of neutrophil into BALF increased gradually and reached a peak 24 h
      after LPS inhalation. After the inhalation of LPS, LTD4 and TNF contents in BALF
      increased within the first 2 h after LPS inhalation. However, other mediators
      were not detected or increased 6 h after LPS inhalation. Aeroinhalation of LTD4
      and murine recombinant TNF-alpha caused airway hyperresponsiveness in guinea
      pigs. In addition, a LTD4 antagonist, BAYx7195, and an inhibitor of TNF,
      pentoxifylline, inhibited the LPS-induced airway hyperresponsiveness. These
      results suggest that LTs and/or TNF play an important role in the onset of airway
      hyperresponsiveness in guinea pigs.

PMID- 9145206
TI  - Comparison of the sympathetic nervous system activity between spontaneously
      hypertensive and Wistar-Kyoto rats to respond to blood pressure reduction.
AB  - Two types of calcium antagonists, diltiazem and nicardipine, were separately
      infused in 23-28 week-old spontaneously hypertensive (SHR) and age-matched
      normotensive Wistar-Kyoto (WKY) rats (under sodium thiobutabarbital anesthesia
      and ventilation, n = 4) through the left femoral vein, resulting in the reduction
      of blood pressure. In each rat, mean arterial blood pressure, heart rate and the
      concentration of plasma catecholamines (CAs), norepinephrine (NE) and epinephrine
      (E), were concomitantly determined and the correlations between these three
      values were studied for each calcium antagonist. Plasma concentration of CAs were
      measured in blood samples collected during the infusion from the right femoral
      artery of each rat by the automatic sensitive and selective detection system. The
      reduction of blood pressure induced by the calcium antagonists brought about an
      increase in plasma CAs levels. The blood pressure correlated well with the
      logarithm of plasma NE and E concentration and the relations were expressed as Y
      = -alpha log(X)+m (Y, blood pressure; X, concentration of plasma NE or E; alpha,
      slope; and m, intercept). The alpha s of SHR rats were greater than those of WKY
      rats for the calcium antagonists employed, meaning that the increment of plasma
      CAs responding to a decrease in blood pressure was smaller in SHR than in WKY
      rats. It was concluded that the contribution of the sympathetic nervous system to
      maintaining blood pressure reduced by diltiazem and nicardipine is less in SHR
      than in WKY rats.

PMID- 9145207
TI  - A modified and convenient method for assessing tumor cell invasion and migration
      and its application to screening for inhibitors.
AB  - In order to screen potent inhibitors of tumor invasion and metastasis, we here
      devised a simple and reproducible in vitro assay for tumor invasion and
      migration. A conventional cell-counting assay using a Transwell chamber with a
      microporous membrane filter is troublesome and time-consuming, involving visually
      counting the cells under a microscope, and the invaded or migrated cells are
      sometimes distributed unevenly in predetermined fields on the lower surface of
      the filter. Therefore, it is difficult to evaluate the invasive and migratory
      abilities of tumor cells easily and quantitatively by the cell counting method.
      In the present study, crystal violet dye was used for staining the invaded cells
      and colorimetrically assessing the invasive ability per filter as an absorbance.
      In this crystal violet assay, tumor cell invasion into a reconstituted basement
      membrane Matrigel was proportional to both the cell number added into the chamber
      and the incubation period, and inversely proportional to the amount of Matrigel
      barrier on the upper surface of filter. The results obtained by this dye-uptake
      method were highly consistent with those of a conventional cell-counting assay.
      Using this crystal violet assay, the anti-invasive effect of doxorubicin (DOX)
      was detected more easily and found to be highly proportional to that by the
      conventional cell-counting method. We therefore applied this convenient assay
      method to screen anti-invasive and anti-metastatic compounds. As a result,
      caffeic acid was found to be more active in the inhibition of both tumor cell
      invasion and migration without showing direct cytotoxicity in vitro than other
      related compounds.

PMID- 9145208
TI  - Possible therapeutic effect of T-794, a novel reversible inhibitor of monoamine
      oxidase-A, on post-stroke emotional disturbances, assessed in animal models of
      depression.
AB  - Emotional disturbances, such as lack of motivation or depression, are common
      after stroke. The drugs mainly used to treat these syndromes in Japan are the
      cerebral metabolic enhancers whose biochemical and pharmacological profiles are
      similar to those of antidepressant drugs. In order to examine the possible
      therapeutic effect of T-794 [(5R)-3-(6-(cyclopropylmethoxy) 2-naphthalenyl)-5
      (methoxymethyl) 2-oxazolidone], a new reversible inhibitor of monoamine oxidase
      (MAO) type A, on those emotional disturbances, its antidepressant activity was
      compared with those of major cerebral metabolic enhancers in rodents with or
      without treatment of cerebral ischemia. Oral administration of T-794 potently
      prevented reserpine-induced ptosis (ED50 = 4.41 mg/kg), akinesia (ED50 = 3.29
      mg/kg), and hypothermia (minimum effective dose = 3 mg/kg) in mice. It was at
      least 3.7, 13.0, and 3.3 times more potent than cerebral metabolic enhancers
      tested (indeloxazine, bifemelane, amantadine and idebenone) in antagonism of the
      ptosis, the akinesia, and the hypothermia, respectively. Effect of T-794 was also
      examined in the behavioral despair test in rats subjected to forebrain ischemia.
      The ischemia was induced by a combination of bilateral common carotid artery
      occlusion (15 min) and systemic hypotension (sodium nitroprusside 5 mg/kg, s.c).
      From 13 d after the surgery, drugs were orally administered twice daily 7 times,
      and following the last administration rats were assessed for their behavior. T
      794 reduced the duration of immobility in the behavioral despair test at 30 mg/kg
      without affecting spontaneous motor activity, whereas indeloxazine showed no
      significant effect. Antidepressant-like activity of T-794 was suggested in
      rodents with as well as those without cerebral ischemia. The results suggest that
      T-794 may make an important contribution to the treatment of emotional
      disturbances following stroke.

PMID- 9145209
TI  - Effect of a new hypoglycemic agent, A-4166 [(-)-N-(trans-4
      isopropylcyclohexanecarbonyl)-D-phenylalanine], on postprandial blood glucose
      excursion: comparison with voglibose and glibenclamide.
AB  - (-)-N-(trans-4-Isopropylcyclohexanecarbonyl)-D-phenylalanine (A-4166) is a new
      nonsulfonylurea hypoglycemic agent that lowers blood glucose by stimulating
      insulin release. In the present study, we examined the effects of A-4166,
      voglibose (an alpha-glucosidase inhibitor), and glibenclamide (a sulfonylurea) on
      the postprandial glycemic increase in rats with or without diabetes mellitus.
      Oral administration of A-4166 (25-100 mg/kg) dose-dependently decreased blood
      glucose with a rapid onset and short duration in normal rats. On the other hand,
      glibenclamide (1-4 mg/kg) showed a slower onset of its hypoglycemic action, and
      voglibose (0.2 mg/kg) had no effect. In the case of postprandial glucose
      excursion, the carbohydrate-induced increase in blood glucose was reduced by oral
      administration of either A-4166 or voglibose without causing sustained
      hypoglycemia in both normal and neonatal streptozotocin-induced diabetic rats.
      However, the efficacy of voglibose varied with the type of carbohydrate load.
      Glibenclamide produced a prolonged decrease in blood glucose without any
      appreciable effect on the initial glucose excursion. After sucrose loading,
      plasma insulin levels during the initial 1 h were significantly higher in A-4166
      treated rats than in control rats, while voglibose completely inhibited the
      insulin response to sucrose. In glibenclamide-treated rats, an augmented insulin
      response was not seen. In conclusion, unlike other hypoglycemic agents, A-4166
      suppresses postprandial glucose excursions by stimulating the early phase of
      insulin secretion.

PMID- 9145210
TI  - Effects of nebracetam on synaptosomal monoamine uptake of striatal and
      hippocampal regions in rats.
AB  - Effects of nebracetam, a novel nootorpic agent, on the synaptosomal uptake of
      neurotransmitter monoamines of the brain regions were examined. Striatal and
      hippocampal synaptosomes were isolated by the Percoll gradient method, and the
      striatal dopamine uptake and hippocampal serotonin uptake were measured in the
      presence of different concentrations (1 to 1000 microM) of nebracetam in vitro. A
      significant reduction in dopamine uptake in the striatum and serotonin uptake in
      the hippocampus was seen at concentrations of 100 microM or above. In in vivo
      microdialysis study, there were no appreciable changes in the extracellular
      concentrations of striatal dopamine and hippocampal serotonin when this agent at
      a dose of 30 mg/kg, which was effective in improving ischemic brain energy
      metabolism, was applied i.p. to the rat. The ineffectiveness of nebracetam in the
      in vivo microdialysis may be due to low levels of the concentration of nebracetam
      when the agent was administered i.p. at a dose of 30 mg/kg, since the brain blood
      concentration of this agent is pharmacokinetically estimated to be no more than
      15 microM when this dose of nebracetam is employed. Thus, it is unlikely that
      this agent at a pharmacologically effective dose alters dopamine or serotonin
      uptake in the brain nerve terminal under normal conditions.

PMID- 9145211
TI  - Cell-nuclear accumulation of 72-kDa stress protein induced by dimethylated
      arsenics.
AB  - The induction and subsequent intracellular distribution of the 72-kDa heat shock
      (stress) protein (Hsp72) by exposure of cultured human alveolar (L-132) cells to
      dimethylarsinic acid (DMAA), a main metabolite of inorganic arsenics in mammals,
      were examined. A significant induction of Hsp72 in the cells was observed by
      exposure to 10mM DMAA for 6 h. The induction was similar to the case by arsenite
      for 6 h or by heat treatment at 42 degrees C for 3h. However, the nuclear
      distribution of Hsp72 differed greatly between DMAA and 42 degrees C treatment or
      arsenite exposure, i.e., Hsp72 induced by exposure to DMAA accumulated not only
      in the nucleoli but also in the nucleoplasm, whereas that by 42 degrees C or
      arsenite exposure did not accumulate in the nucleoplasm. Furthermore, the Hsp72
      accumulated in the nucleus by DMAA exposure hardly diffused with the addition of
      ATP, suggesting that the DMAA-induced Hsp72 strongly binds to some macromolecules
      in the nucleus. The fact that Hsp72 induced by DMAA exposure accumulated in the
      nucleus of the cells may reflect a protective response toward the nucleus
      specific damaging action of dimethylarsenics.

PMID- 9145212
TI  - Basic studies on 5-(7-hydroxy-3-O-phosphonocholyl)aminosalicylic acid for the
      evaluation of microbial overgrowth.
AB  - A newly synthesized conjugate of 7-hydroxy-3-O-phosphonocholic acid
      (ursodeoxycholic acid monophosphate) with 5-aminosalicylic acid (5-ASA-UDCA
      monophosphate) was investigated to determine its suitability for the evaluation
      of enteric bacteria. This compound, 5-ASA-UDCA monophosphate, was efficiently
      deconjugated by cholylglycine hydrolase to release 5-ASA, whereas it was
      completely resistant to deconjugation by pancreatic and intestinal mucosal
      enzymes. In everted gut sac experiments, 5-ASA-UDCA monophosphate was not
      actively absorbed from any part of the small intestine. In animal experiments,
      urinary excretions of N-acetyl-5-ASA (Ac-5ASA) were measured for 24 h following
      the oral administration of 20 mg of 5-ASA-UDCA monophosphate. Control rats
      excreted 276.3 +/- 89.0 micrograms (mean +/- S.E.) of Ac-5ASA, whereas the rats
      with intestinal bacterial overgrowth excreted more (1224.1 +/- 231.5 micrograms;
      p < 0.01). These basic studies indicate that this compound is likely to offer a
      simple method for the evaluation of microbial overgrowth without the use of
      radioisotopes or expensive, special apparatus.

PMID- 9145213
TI  - The effect of keishi-bushi-to on collagen-induced arthritis.
AB  - To evaluate the usefulness of a traditional Chinese medicine (Kampo
      prescription), Keishi-bushi-to (KBT), which is composed of five medicinal plants
      derived from Kampo prescriptions used to treat rheumatoid arthritis, we
      investigated the effect of KBT on the development of arthritis induced by type II
      collagen (CII). Oral administration of KBT at a dose of 500 mg/kg from 7 d before
      intradermal injection of CII significantly reduced the severity from 7 d after
      the onset of arthritis. The reduction in body weight resulting from the
      development of arthritis was not seen in rats treated with KBT. Plasma IgG and
      IgM anti-CII antibody levels were lower in KBT-treated rats than control rats. In
      addition, the clearance of IgG anti-CII antibody from circulating blood after
      intravenous injection was faster in KBT-treated rats than control rats. These
      results indicate that KBT is effective in suppressing collagen-induced arthritis
      and its effect is at least partly due to the suppression of humoral and cellular
      immunity.

PMID- 9145214
TI  - Hepatoprotective effect of Hovenia dulcis THUNB. on experimental liver injuries
      induced by carbon tetrachloride or D-galactosamine/lipopolysaccharide.
AB  - The hepatoprotective effects of the fruits of Hovenia dulcis THUNB. on chemically
      or immunologically induced experimental liver injury models were examined. The
      methanol extract showed significant hepatoprotective activity against CCl4
      toxicity in rats and D-galactosamine (D-GalN)/lipopolysaccharide-induced liver
      injury in mice. The methanol extract also significantly protected against CCl4
      toxicity in primary cultured rat hepatocytes. Hepatoprotective activity-guided
      fractionation and chemical analysis led to the isolation of an active
      constituent, (+)-ampelopsin (1) from the methanol extract.

PMID- 9145215
TI  - Effects of betamipron on cisplatin nephrotoxicity and its pharmacokinetics in
      rats.
AB  - The protective effects of betamipron (BP, N-benzoyl-beta-alanine) on the
      nephrotoxicity of cisplatin were examined as indicated by body weight gain, ratio
      of kidney weight to body weight, blood urea nitrogen and serum creatinine levels
      in tumor-bearing rats. The results showed clearly that administration of BP 1 h
      after cisplatin treatment affords protection against the nephrotoxicity of
      cisplatin. Furthermore, the addition of BP to cisplatin had no apparent effect on
      the efficacy of cisplatin against Walker 256 carcinosarcoma cells in rats. In
      addition, no observed significant difference in plasma cisplatin concentration
      between cisplatin with alkaline solution and cisplatin with BP may be partly
      attributed to the decrease in the cisplatin exsorption to the intestine and its
      excretion to bile, and to an increase in cisplatin excretion to the urine.

PMID- 9145216
TI  - First-pass metabolism of ONO-5046 (N-[2-[4-(2,2-dimethylpropionyloxy)
      phenylsulfonylamino]benzoyl]aminoacetic acid), a novel elastase inhibitor, in
      rats.
AB  - The first-pass metabolism in the intestine and liver of ONO-5046 (N-[2-[4-(2,2
      dimethylpropionyloxy)-phenylsulfonylamino]benz oyl]aminoacetic acid), a newly
      synthesized elastase inhibitor, was separately estimated in rats. When ONO-5046
      solution was administered into the whole intestine via the bile duct at a dose of
      5 mumol/rat, the extent of bioavailability was only 1.5%. A small but significant
      increase in the bioavailability with an increase in the dose suggested marked
      first-pass metabolism with a saturable process. Hepatic first-pass metabolism was
      estimated by determining the hepatic extraction ratio of ONO-5046 after
      administration into the portal vein at two different infusion rates (5 mumol/kg/9
      min or 5 mumol/kg/20s). The extraction ratio was relatively small and constant
      (about 20%) under 2 different infusion rates of the drug. Intestinal first-pass
      metabolism was estimated by determining the drug recovery in the mesenteric
      plasma after administering the drug into the intestinal loop in situ (mesenteric
      blood collecting method in situ). The recovery percentage of ONO-5046 in the
      mesenteric plasma was small (2.58 +/- 0.04% at a dose of 1 mumol/rat), and the
      remaining ONO-5046 recovered in the mesenteric plasma and in the intestinal loop
      was a metabolite of ONO-5046 (El-601, N-[2-[(4
      hydroxyphenyl)sulfonylamino]benzoyl]amino-acetic acid). Recovery percentage of
      ONO-5046 in the mesenteric plasma increased significantly with an increase in the
      dose, although the recovery percentage was still low, even at a higher dose (9.55
      +/- 1.17% of dose at a dose of 5 mumol/rat). These results indicate that the low
      oral bioavailability of ONO-5046 in vivo is mainly due to the marked intestinal
      first-pass metabolism, including the metabolism in the intestinal fluid, and the
      dose-dependent oral bioavailability was derived from the saturable intestinal
      first-pass metabolism.

PMID- 9145217
TI  - Phenobarbital molecularly imprinted polymer selectively binds phenobarbital.
AB  - Molecularly imprinted polymer (MIP) was prepared against phenobarbital using
      methacrylic acid as the functional monomer and ethylene glycol dimethacrylate as
      the cross linking monomer. We analyzed the recognition properties of the
      phenobarbital MIP. In some organic solvents, imprinted polymer showed selective
      binding to phenobarbital. Two dissociation constants of binding were calculated
      by Scatchard plot analyses; Kd values were 1.8, 121.7 microM, and the number of
      binding sites was 8.3, 92.3 mumol/g MIP in toluene-heptane-acetic acid (25 : 75 :
      1, v/v), respectively. The relationship between the binding affinity to
      phenobarbital MIP and the polarity of the solvent system, as well as the
      structure of the template molecule is also discussed.

PMID- 9145218
TI  - Extraction and purification of effective antimicrobial constituents of Terminalia
      chebula RETS. against methicillin-resistant Staphylococcus aureus.
AB  - Examination of the EtOH extract of the fruiting bodies of Terminalia chebula
      RETZ. led to the isolation of two potent antimicrobial substances against even
      methicillin-resistant strains of Staphylococcus aureus. On the basis of
      spectroscopic evidence, the two isolates have been identified as gallic acid and
      its ethyl ester.

PMID- 9145219
TI  - Pharmacokinetic analysis of enterohepatic circulation of etodolac and effect of
      hepatic and renal injury on the pharmacokinetics.
AB  - This study was designed to evaluate the enterohepatic circulation of racemic
      etodolac in rats. Additionally, the effect of hepatic and renal failure on the
      pharmacokinetics was estimated. The biliary excretion and the reabsorption of the
      drug excreted in bile were examined in order to clarify the effect of
      enterohepatic circulation on the disposition, and a pharmacokinetics model was
      applied to describe the enterohepatic circulation. The relatively rapid
      elimination of etodolac was seen in the bile-exteriorized rats (BE rat) compared
      with that in control rats. Total biliary excretion of etodolac, mainly as
      glucuronides, after intravenous administration was about 45% of the dose,
      indicating extensive enterohepatic circulation of the drug. The plasma
      concentrations of the drug in bile duct-linked rats approximately agreed with the
      simulation curve by the model, with the peak concentration 6-7 h after dosing.
      The elimination of the drug was markedly retarded in rats with hepatic (CCI4
      induced) and renal (uranyl acetate-induced) failure, and high plasma levels were
      maintained over the longer times, due to greatly decreased distribution volume.
      The biliary excretion of etodolac enantiomers was not significantly different
      between the control and CCI4-groups, suggesting that hepatic glucuronyl
      transferase activity was preserved in rats impaired by CCI4.

PMID- 9145220
TI  - Effects of erythromycin, clarithromycin and rokitamycin on nifedipine metabolism
      in rats.
AB  - The effects of erythromycin, clarithromycin and rokitamycin on the metabolism of
      nifedipine were studied in vitro and in situ. Erythromycin, clarithromycin or
      rokitamycin added to nifedipine did not inhibit the formation of metabolite, M-1,
      of nifedipine, whereas pretreatment with erythromycin or clarithromycin
      significantly (p < 0.05) inhibited its formation. Only erythromycin significantly
      (p < 0.05) inhibited the formation of M-2 from M-1. These observations agreed
      with the results obtained using an in situ rat intestinal loop technique. As
      assessed by the concentrations of nifedipine and M-2 in jugular and portal vein
      blood, the inhibition of nifedipine metabolism by erythromycin was greater after
      multiple doses than after a single dose. Moreover, our results suggest that
      rokitamycin is a less potent inhibitor of nifedipine metabolism.

PMID- 9145221
TI  - Antifibrotic effects of a polysaccharide extracted from Ganoderma lucidum,
      glycyrrhizin, and pentoxifylline in rats with cirrhosis induced by biliary
      obstruction.
AB  - For the past few years, we have been investigating polysaccharides from Ganoderma
      lucidum as antifibrotic agents. In a previous study, we discovered that
      polysaccharides extracted from G. Iucidum lowered the collagen content in liver
      but had no effect on serum biochemical parameters in rats subjected to bile duct
      ligation and scission-induced fibrosis. In this study, we changed the extraction
      method and obtained polysaccharides extracted from G. Iucidum. The polysaccharide
      from G. Iucidum reduced the serum aspartate transaminase (AST), alanine
      transaminase (ALT), alkaline phosphatase (ALP) and total bilirubin and also
      reduced the collagen content in liver and improved the morphology.
      Pentoxifylline, which is reported to exhibit an antifibrotic effect in pigs with
      fibrosis induced by yellow phosphorus, did not have any antifibrotic effects in
      fibrosis induced by biliary obstruction. Glycyrrhizin, which is used in the
      treatment of hepatitis, reduced serum ALT and AST values but there was no
      significance. It had no effect on liver hydroxyproline content which implies that
      glycyrrhizin has no antifibrotic effect in the rats with fibrosis induced by bile
      duct ligation and scission. These data suggest that the polysaccharide from
      Ganoderma lucidum could be a promising antifibrotic agent. However, further study
      is needed to understand the inhibition mechanism of collagen deposition of
      polysaccharides from Ganoderma Iucidum and its clinical applicability remains to
      be established.

PMID- 9145222
TI  - Relationship between amount of beta-blockers permeating through the stratum
      corneum and skin irritation after application of beta-blocker adhesive patches to
      guinea pig skin.
AB  - We evaluated the relationship between the cumulative amounts of 5 kinds of beta
      blockers (alprenolol, oxprenolol, timolol, acebutolol and atenolol) permeating
      through the stratum corneum and a* values obtained by measuring the formation of
      erythema, a skin irritation reaction, with a chromameter after transdermal
      application of adhesive patches containing 2 beta-blocker to the skin of guinea
      pigs. The cumulative amount of beta-blocker released from each adhesive patch to
      the skin increased with the increase in application time. The contents of
      alprenolol, oxprenolol and timolol in the stratum corneum and in the stripped
      skin increased markedly up to 4 h after application and thereafter were
      maintained at high levels up to 24 h. The contents of acebutolol and atenolol, on
      the other hand, increased up to 24 h, but these values were low. a* values of all
      adhesive patches 24 h after application were higher than those before
      application. The correlation coefficients between the cumulative amounts of
      alprenolol, oxprenolol, timolol, acebutolol or atenolol permeating through the
      stratum corneum and (delta a* -delta a*Placebo) values were 0.739, 0.717, 0.722,
      0.551 and 0.633, respectively. The correlation coefficient calculated by
      averaging the cumulative amounts of 6 kinds of beta-blockers permeating through
      the stratum corneum [including propranolol which was reported previously
      (Kobayashi I., et al., Biol. Pharm. Bull., 19, 839-844 (1996))] was 0.731, higher
      than the correlation coefficient between contents of these beta-blockers in the
      stripped skin and (delta a* -delta a*Placebo) values (r = 0.552). This suggests
      that there was a high correlation between the cumulative amounts of beta-blockers
      permeating through the stratum corneum and (delta a* -delta a*Placebo) values.

PMID- 9145224
TI  - Inhibitory effects of dehydrocorydaline isolated from Corydalis Tuber against
      type I-IV allergic models.
AB  - An alkaloidal component, dehydrocorydaline (DHC) isolated from Corydalis Tuber
      (tuber of Corydalis turtschaninovii forma yanhusuo), has been screened for
      activity against types I-IV allergic reactions. In a type I allergic models, DHC
      at a dose of 0.5 mmol/kg, p.o. inhibited 48 h homologous passive cutaneous
      anaphylaxis (PCA) in rats, which is related to IgE. DHC also exhibited an
      inhibitory effect on antigen-induced histamine release from peritoneal mast
      cells. In a type II allergic model, DHC did not inhibit reversed cutaneous
      anaphylaxis (RCA) in rats. In a type III allergic model, DHC showed weak
      inhibition on direct passive arthus reaction (DPAR) in rats. Furthermore, in a
      type IV allergic model, DHC had inhibitory effects on the induction phase and
      effector phase in picryl chloride-induced contact dermatitis (PC-CD). These
      results indicated that DHC not only inhibits antibody-mediated allergic reactions
      but also influences cell-mediated allergia reactions, and the inhibitory effect
      of Corydalis Tuber on allergic reactions may be partially attributed to DHC.

PMID- 9145223
TI  - Influence of OSW-1 [3 beta,16 beta,17 alpha-trihydroxycholest-5-en-22-one 16-O-(2
      O-4-methoxybenzoyl-beta-D-xylopyranosyl)-(1--> 3)-(2-O-acetyl-alpha-L
      arabinopyranoside)], a steroidal saponin, on endothelium dependent relaxation
      caused by acetylcholine in rat aorta.
AB  - The tension of isolated ring preparation of the aorta from rats was measured
      isometrically to study the influence of OSW-1 [3 beta,16 beta,17 alpha
      trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-beta-D-xylopyranosyl)-(1
      right arrow 3)-(2-O-acetyl-alpha-L-arabinopyranoside)], a steroidal saponin, on
      the endothelium dependent and independent relaxation caused by acetylcholin (ACh)
      and sodium nitroprusside (SNP), respectively. OSW-1 (10(-7) M), which has more
      than 100 times higher concentration for anti-tumor activity, had no influence on
      either the endothelium dependent or independent relaxation. OSW-1 (10(-6) M, 0.9
      microgram/ml) slightly reduced the endothelium dependent relaxation caused by ACh
      but did not affect the SNP-induced relaxation. In contrast to OSW-1, 1 mg/ml of
      saponin significantly suppressed the ACh-induced relaxation and shifted the dose
      relaxation curve for SNP to the right. OSW-1 (10(-7) and 10(-6) M) did not affect
      the norepinephrine-induced contraction but 1 mg/ml of saponin significantly
      attenuated it. The results suggest that though the higher concentration of OSW-1
      shows weaker influence on the endothelium function compared with saponin, OSW-1
      at an anti-tumor dose has no influence on either endothelium or smooth muscle
      function.

PMID- 9145226
TI  - Relationship between pharmacokinetics and the analgesic effect of indomethacin in
      the rat.
AB  - The relationship between the pharmacokinetic properties and the analgesic effect
      of indomethacin (IDM) was evaluated on a carrageenin-induced inflammation model
      in the rat. Rats were administered the drug in one of two ways: intravenous
      (i.v.) IDM bolus or i.v. IDM infusion. The analgesic activity was measured by
      Randall-Selitto test. No correlation was observed between the analgesic effect
      and the plasma IDM concentration after i.v. bolus administration of IDM. However,
      in the case of infusion, IDM produced a dose-dependent analgesic effect. In this
      paper, we demonstrated that the plasma concentration of IDM maintained by i.v.
      infusion had a prolonged analgesic effect on the carrageenin-induced inflammation
      model.

PMID- 9145225
TI  - Effect of karasurin-A on nitric oxide production by murine macrophages and
      mitogenic response of murine splenocytes in vitro.
AB  - We studied the effect of karasurin-A, a type-I ribosome-inactivating protein
      (RIP) isolated from fresh root tubers of Trichosanches kirilowii MAX. var.
      japonica KITAMURA, on the mitogenic response of murine splenocytes and nitric
      oxide (NO) production by murine peritoneal macrophages in vitro. Karasurin-A
      inhibited the lymphocyte proliferation by LPS, ConA and PHA and NO production by
      LPS at non-cytotoxic concentrations (10-1000 ng/ml for splenocytes and 10-100
      ng/ml for macrophages, respectively). These data suggest that karasurin-A has
      immunosuppressive activity in vitro.

PMID- 9145227
TI  - Urinary excretion of mefenamic acid and its metabolites including their
      esterglucuronides in preterm infants undergoing mefenamic acid therapy.
AB  - Urinary excretion of mefenamic acid (MA) and its two oxidative metabolites, M-I
      (3'-hydroxymethyl derivative) and M-II (3'-carboxyl derivative), and their
      glucuronides was investigated in preterm infants undergoing MA therapy. MA was
      given orally at a dose of 2 mg/kg and the dose was repeated every 24 h a maximum
      of three times. Urine was collected for up to 5 d after the last dose, and MA and
      the metabolites were determined by a newly developed HPLC. The cumulative amounts
      of MA and the metabolites excreted in the urine varied from 7 to 46% of the total
      dose administered, and were less than those reported in adults and children.
      Significant correlation was observed between the plasma half-life of MA and the
      cumulative amount of MA and the metabolites excreted in the urine. These results
      suggest that long plasma half-lives of MA observed in preterm infants are due
      mainly to low activity of drug metabolizing enzyme(s). In an infant who received
      the two regimens of MA therapy about 2 weeks apart, the plasma half-life of MA
      was shortened and the urinary excretion of the MA metabolites including their
      glucuronides was greatly increased during this period. It is suggested that the
      activities of both cytochrome P-450(s) and glucuronyltransferase(s) related to MA
      metabolism rapidly increased during the first month of the infant's life.

PMID- 9145228
TI  - The enhancing mechanism of capric acid (C10) from a suppository on rectal drug
      absorption through a paracellular pathway.
AB  - Capric acid (C10) enhanced the absorption of cefoxitin sodium in a concentration
      dependent manner following the rectal administration as a suppository in rats.
      The optimal concentration of C10 was 13%. C10 administered as a suppository also
      reduced rectal membrane resistance (Rm), showing that the above enhancing effect
      was induced by widening the paracellular pathway. Both the enhancing effect on
      the absorption and the reducing effect on Rm were inhibited by W7, an inhibitor
      of myosin light chain kinase. These results supported that, as shown in the in
      vitro Caco-2 cell system, the C10 effect on the paracellular pathway is due to
      activating the contraction of Ca(2+)-calmodulin-dependent actin filament.

PMID- 9145229
TI  - Inhibitory effects of angiotensin-converting enzyme inhibitor on cefroxadine
      uptake by rabbit small intestinal brush border membrane vesicles.
AB  - Effects of angiotensin-converting enzyme (ACE) inhibitors, captopril, enalapril
      maleate and quinapril, on the uptake of aminocephalosporin antibiotic,
      cefroxadine, by rabbit small intestinal brush border membrane vesicles were
      examined. These ACE inhibitors significantly inhibited the uptake of cefroxadine,
      which is transported by H+/dipeptide transporter in the membrane, in the order of
      captopril < enalapril < quinapril in the presence of an inward H+ gradient.
      Inhibitory effect of quinapril was more marked than that of aminocephalosporin
      cephradine, while in the absence of an inward H+ gradient inhibition by these ACE
      inhibitors was much less. Dixon plot analysis showed that the inhibition by
      enalapril and quinapril in the presence of an inward H+ gradient occurred in a
      competitive manner and estimated inhibition constants of these two drugs to be
      5.3 mM and 0.46 mM, respectively. These results suggested the strong affinity of
      these ACE inhibitors, especially quinapril, on the H+/dipeptide transporter.

PMID- 9145230
TI  - Effect of N-B transition on the microenvironment surrounding 34Cys in human serum
      albumin.
AB  - The effect of pH on the microenvironment surrounding 34Cys in human serum albumin
      (HSA) has been studied using acrylodan, a Cys-specific fluorescence probe. The
      reactivity of 34Cys with 5,5'-dithiobis(2-nitro benzoic acid) (DTNB) followed a
      pseudo-first-order reaction, and the increase in reactivity was dependent on pH
      and oleate content. Compared with the N-form of HSA-acrylodan conjugate (pH 6.2),
      the B-form (pH 8.4) has a blue-shifted Emmax and enhanced fluorescence intensity
      derived from acrylodan covalently attached to 34Cys suggesting that the exposure
      around 34Cys in the B-form was less than that in the N-form. The conformational
      change induced by fatty acid increased the exposure around 34Cys, while that
      induced by an increase in pH decreased it. Further, since the effect of oleate on
      the fluorescence of acrylodan was nearly the same for both conformers, the
      effects of pH and oleate on the microenvironment surrounding 34Cys should be
      independent and additive. We concluded that the increase of reactivity of 34Cys
      as a function in increasing pH may well be related to an increase in mercaptide
      ion content.

PMID- 9145231
TI  - Release behavior of poly(lactic acid-co-glycolic acid) implants containing
      phosphorothioate oligodeoxynucleotide.
AB  - The release behavior of phosphorothioate oligodeoxynucleotide, 5'
      GCCGAGGTCCATGTCGTACGC-3' (ODN), from poly(lactic acid-co-glycolic acid) (PLGA)
      implant was studied. The pillar shape implant was fabricated by the heating mold
      method. About 20% of ODN were released initially, and the subsequent pseudo-zero
      order release lasted for more than 20 d from a PLGA10000 implant loaded with 8.4%
      ODN in phosphate buffered saline, pH 7.4. The duration of ODN release did not
      depend on the molecular weights of PLGA, and pseudo-zero-order release may be
      achieved by changing the loaded amount of ODN in fabrication of the PLGA implant.
      Almost the same release profiles were obtained in the pH range of 7.2 to 7.6,
      which is known as the physiological pH of a vitreous body. Furthermore, the
      duration of intact ODN release in bovine vitreous was found. The implant in the
      present study may possibly be applicable to intravitreal implantation for the
      treatment of ocular disease.

PMID- 9145232
TI  - Improvement of dissolution rate and oral bioavailability of a sparingly water
      soluble drug, (+/-)-5-[[2-(2-naphthalenylmethyl)-5-benzoxazolyl]-methyl]- 2, 4
      thiazolidinedione, in co-ground mixture with D-mannitol.
AB  - We investigated the usefulness and efficiency of the co-grinding method with D
      mannitol to improve the bioavailability of a sparingly water-soluble drug, (+/-)
      5-[[2-(2-naphthalenylmethyl)-5-benzoxazolyl]methyl]-2, 4-thiazolidinedione (174),
      and compared it with those of the single-grinding method. The co-ground mixtures
      in drug/carrier weight ratios up to 1:5 gave fine particle sizes of less than
      about 3 microns, which showed a marked increase in the dissolution rate with
      reduction of particle size, compared with the single-ground powder, even with a
      similar particle size. The oral bioavailability study of co-ground powders in
      beagle dogs exhibited a dramatic increase, as did the dissolution rate, according
      to finer particle size. Finally, complete bioavailability was obtained at the
      finest particle size of 1.2 microns (drug/carrier ratio of 1:5, w/w) as was a
      solution of the drug. Bioavailability had a good linear correlation with the
      dissolution rate. These findings suggested that the co-grinding method with D
      mannitol dramatically increased the available surface area, caused by a reduction
      of particle size, which not only accelerated the dissolution rate but also
      resulted in greater enhancement of the bioavailability of 174.

PMID- 9145233
TI  - Screening for bioactive compounds targeting the cellular signal transduction
      pathway using an RT-PCR-based bioassay system.
AB  - A novel bioassay system based on RT-PCR has been established to search for
      biologically active compounds which can modulate the expression of genes encoding
      important regulatory proteins. Changes in target mRNA level in the treated cell
      cultures were quantitatively determined by competitive PCR using internal
      standard DNA. The compounds discovered using this bioassay will be useful tools
      to elucidate the mechanisms of cellular signaling guiding the expression of the
      target genes. As the first application of the new bioassay strategy, the
      expression of the interleukin-2 gene in Jurkat cells, a human T cell line, was
      investigated. Screening of several crude drugs used in traditional Chinese
      medicines demonstrated that the aqueous acetone extract of Coptidis Rhizoma
      enhanced the expression of the interleukin-2 gene by about 5-fold as compared to
      the control.

PMID- 9145234
TI  - Defining osteopenias and osteoporoses: another view (with insights from a new
      paradigm).
AB  - This article suggests classifying "osteoporoses" by their biomechanical
      pathogenesis instead of by their severity or their accompanying medical
      conditions. (A) In a "true osteoporosis," bone fragility would increase to such
      an extent that normal physical activity would cause spontaneous fractures and/or
      a bone pain syndrome, mainly affecting the spine; however, falls could also cause
      extremity bone fractures. (B) In a "physiologic osteopenia," reduced bone
      strength and "mass" would fit correspondingly reduced physical activities and
      muscle strength so well that fractures would not happen without falls or other
      injuries. Those fractures would affect extremity bones more than the spine. (C)
      In "combination states," features of (A) and (B) would combine variably. (D)
      "Transient osteopenias" would occur while serious injuries heal. After healing,
      transient osteopenias usually resolve without treatment, and fractures occur only
      from injuries. While an osteopenia's severity usually affects the risk of
      fracture, its pathogenesis could strongly affect the treatment needed for
      prevention or cure.

PMID- 9145235
TI  - Mineralization of cancellous bone after alendronate and sodium fluoride
      treatment: a quantitative backscattered electron imaging study on minipig ribs.
AB  - Fluoride stimulates bone formation, whereas bisphosphonates reduce bone
      resorption. In clinical trials, both treatments increase bone density, although
      sodium fluoride (NaF) increases and alendronate (bisphosphonate, ALN) decreases
      bone turnover. In a comparative study using minipigs an inverse correlation has
      been reported between bone turnover and elastic modulus. Small-angle X-ray
      scattering (SAXS) measurements of these bones revealed no structural
      deterioration of the collagen/mineral composite at the nanometer range for ALN
      treated vertebra, whereas a slight increase of the average thickness of the
      mineral crystals as well as changes of the structure of the collagen/mineral
      composite were found in the bones of NaF-treated animals. In this study we used
      quantitative backscattered electron imaging (qBSE) to investigate the cancellous
      bones from ribs of minipigs treated with vehicle, NaF, or ALN. This method
      provides information on the local mineral concentration in the micrometer range.
      Mineralization spectra were obtained from each treatment group, and statistically
      significant differences between ALN and controls were found for the peak
      position, the peak height, the peak width, and the average calcium (Ca)
      concentration of the mineral distribution. The results reveal that the cancellous
      bone matrix was more uniformly mineralized after ALN treatment. The reduced bone
      turnover induced by ALN, documented histomorphometrically could be at the origin
      of this phenomenon. No significant differences were detected between NaF and
      control. Together with the earlier SAXS data these results may explain in part
      the increase in bone density and the improvement of biomechanical properties
      observed after ALN treatment in animals and in osteoporotic patients.

PMID- 9145236
TI  - Tiludronate inhibits protein tyrosine phosphatase activity in osteoclasts.
AB  - Signaling pathways mediated by tyrosine phosphorylation and dephosphorylation
      have been reported to be involved in the regulation of cytoskeletal organization
      in osteoclasts, the principal cells responsible for bone resorption. We examined
      the effects of tiludronate [(4-chlorophenyl)thiomethylene bisphosphonate] on the
      cytoskeleton and the balance of phosphotyrosine levels in osteoclast-like
      multinucleated cells (OCLs) formed in cocultures of mouse osteoblastic cells and
      bone marrow cells. When OCLs were placed on plastic dishes in the presence of 10%
      fetal bovine serum, they formed a ringed structure of F-actin dots (actin ring)
      within 2 h. Tiludronate did not inhibit the process of actin ring formation, but
      it disrupted preformed actin rings in a time- and a dose-dependent manner.
      Western blot analysis using an antiphosphotyrosine antibody revealed that
      tyrosine phosphorylation of certain proteins in OCLs was stimulated by
      tiludronate added to the purified OCLs. Tyrosine kinase activity of the p60c-src
      immunoprecipitated from cell lysates of the purified OCLs was not affected by
      tiludronate directly added to the kinase assay. OCL lysates stimulated
      dephosphorylation of tyrosine-phosphorylated substrates such as
      phosphoneuroprotein 14 and epidermal growth factor receptors. Like sodium
      orthovanadate, an inhibitor of protein tyrosine phosphatases, tiludronate dose
      dependently inhibited tyrosine dephosphorylation of those substrates induced by
      OCL lysates. These findings suggest that tiludronate disrupts the preformed actin
      rings and suppresses bone-resorbing activity by inhibiting protein tyrosine
      phosphatases in osteoclasts.

PMID- 9145237
TI  - Pamidronate content and turnover in sternum, vertebral body, and iliac bones of
      dogs.
AB  - Therapeutic efficacy of bisphosphonates depends on how much drug is present in
      bone. Therefore, it is important to measure the amount of bone bisphosphonate in
      toxicological and pharmacological studies. We analyzed pamidronate content of
      bone samples from two previously published long-term dose studies. In the first
      study, mature beagle dogs were given oral pamidronate at doses of 0, 2.5, 12.5
      and 25 mg/kg per day for 1 year. The dogs in the second study received the same
      dosages for 1 year followed by 1 year without drug. In both studies, the amount
      of pamidronate measured was dependent upon dose in bone samples of ilium,
      sternum, and vertebral body. After 1 year of treatment, vertebral bone had more
      pamidronate than sternum or iliac bone on a permilligram basis. After 2 years,
      there was significantly less pamidronate in the vertebral body, sternum, and
      ilium than there had been at 1 year. The fall in pamidronate content was largest
      in vertebral body and least in the ilium. The higher uptake of pamidronate by the
      vertebral body during the 1 year study, and its greater loss of pamidronate after
      a year without drug treatment, would reflect the higher turnover of trabecular
      bone in the vertebral body vs. cortical bone in the ilium. The percent difference
      in bone pamidronate content between the 1 and 2 year dogs varied with dose. The
      largest percent loss occurred in the intermediate-dose group. These data suggest
      that, after 1 year without the drug, bone turnover rates in dogs treated with the
      highest dose of pamidronate were lower than at the intermediate dose. Thus, the
      time required for bone turnover rates to return to pretreatment levels is
      probably dose-dependent.

PMID- 9145238
TI  - Effects of 17 beta-estradiol administration on cortical and cancellous bone of
      ovariectomized rats with and without hypophysectomy.
AB  - Pituitary hormones are essential for bone growth and bone turnover.
      Hypophysectomy (HX) diminishes mitogenesis and abolishes the high bone turnover
      rate induced by ovariectomy (OV). It is not known whether the suppressive effect
      of estrogen on bone resorption is diminished or abolished by HX. The present
      study investigates the effects of 17 beta-estradiol (E2) (20 micrograms/wk) on
      cortical and cancellous bone mass and bone turnover as measured by
      histomorphometry in HX + OV (HO) rats. Sprague-Dawley rats at 2 months of age
      were OV or HO and the experiment was performed over a 6 week period.
      Hypophysectomy + OV (HO) resulted in a cessation of periosteal bone formation,
      and longitudinal bone growth and a decrease in cancellous bone volume. The tibial
      dry weight and tibial density were significantly lower in the HO than in the
      intact or OV groups. Administration of E2 to HO rats partially prevented
      cancellous bone loss, whereas the same dosage of E2 fully prevented cancellous
      bone loss in rats with OV alone. Nevertheless, cancellous bone volume was higher
      in the HO + E2 than in the HO-alone groups. Estradiol administration in HO rats
      did not suppress cancellous bone formation rate or the eroded surface as much as
      it did in the OV rats. The suppressive effect of E2 on periosteal bone formation
      rate and mineral apposition rate was also diminished in HO rats. However,
      factorial ANOVA showed that the effects of E2 on increasing cancellous bone
      volume and decreasing periosteal bone formation rate and mineral apposition rate
      were still significant in the HO rats. Tibial dry weight and tibial density did
      not differ between HO and HO + E2 groups. In conclusion, we have demonstrated
      that the estrogen-induced effects of preventing cancellous bone loss, of
      suppressing bone formation, and resorption as seen in OV rats was diminished but
      not abolished in HO rats.

PMID- 9145240
TI  - No loss of biomechanical effects after withdrawal of short-term PTH treatment in
      an aged, osteopenic, ovariectomized rat model.
AB  - The aim of the study was to assess the biomechanical effects of short-term PTH
      treatment and withdrawal on bone mass and strength in an aged, osteopenic,
      ovariectomized (ovx) rat model. Additionally, the effect of sequential therapy
      with PTH and the bisphosphonate, risedronate, the effect of longterm PTH
      monotherapy, and the effect of long-term risedronate monotherapy were assessed.
      96 4-month-old rats were randomized into nine groups. Eight groups were
      ovariectomized and one group was sham operated. 12 months after surgery,
      treatment regimens were initiated (OW) and were continued for either 2 weeks (2
      W) or 12 weeks (12 W). The treatment regimens were as follows: (1) baseline ovx
      (OW); (2) ovx-saline (2 W); (3) ovx-PTH 1-34 (2 W); (4) intact-saline (12 W); (5)
      ovx-saline (12 W); (6) ovx-risedronate (12 W); (7) ovx-PTH 1-34 (12 W); (8) ovx
      PTH 1-34 (2 W), followed by pause (10 W); and (9) ovx-PTH 1-34 (2 W), accompanied
      by risedronate (12 W). The effect of therapy (endpoint) was measured at three
      skeletal sites: vertebral bodies; femoral cortical bone; and femoral necks. The
      results revealed an anabolic, time-dependent effect of PTH 1-34 at all skeletal
      sites. No loss of anabolic effect was observed 10 weeks after discontinuation of
      2 week PTH treatment in this rat model. Risedronate given in sequential therapy
      with PTH produced no significant effect on biomechanical properties at any
      skeletal sites when compared with 2 week PTH followed by a 10 week pause.
      However, when risedronate was given alone, a positive effect was seen at the
      vertebral site after a 12 week treatment. On the basis of this study with short
      term PTH treatment of aged, osteopenic, ovariectomized rats, there seemed to be a
      significant effect of PTH on the biomechanical properties and no loss of effect
      even 10 weeks after PTH withdrawal.

PMID- 9145239
TI  - Effects of long-term diabetes and/or high-dose 17 beta-estradiol on bone
      formation, bone mineral density, and strength in ovariectomized rats.
AB  - Long-term diabetes in female rats preserves the bone mineral density (BMD) but
      impairs the strength of the femur. In this study, we have compared the effects of
      diabetes and high-dose 17 beta-estradiol (E2), two conditions of low bone
      formation, in ovariectomized (ovx) rats. Spontaneously diabetic BB rats were ovx
      0-3 days after onset, and nondiabetic ovx littermates were used as controls; the
      rats were either untreated or treated with E2 (30 micrograms/day,
      subcutaneously), for 6 or 12 weeks (n = 9 in each of the eight groups). Analysis
      included: plasma 1,25-dihydroxyvitamin D3, insulin-like growth factor-I (IGF-I),
      and osteocalcin concentrations; histomorphometry of the proximal tibial
      metaphysis (PTM); and DXA and biomechanical testing of the femur. Both E2
      treatment and diabetes markedly lowered plasma IGF-I and osteocalcin
      concentrations, as well as dynamic morphometric parameters of bone formation in
      the PTM. Plasma IGF-I and osteocalcin were correlated (R2 = 0.55; p < 0.0001). E2
      treatment in both control and diabetic ovx rats increased the trabecular bone
      volume in the PTM and the BMD in the metaphysis of the distal femur; there was no
      difference between control and diabetic rats, however. The diaphyseal area and
      BMC were decreased in E2-treated or/and diabetic ovx rats, but the diaphyseal BMD
      remained unchanged compared with untreated ovx rats. The biomechanical properties
      of the whole femur (strength, angular deformation, and stiffness) were decreased
      in E2-treated and diabetic E2-treated ovx rats after 12 weeks. The data indicate
      that in situations of chronic low bone formation, whole bone strength does not
      reflect total BMD but correlates better with bone size and bone mineral content
      measurements.

PMID- 9145241
TI  - A comparison of the effects of two anabolic agents (fluoride and PTH) on ash
      density and bone strength assessed in an osteopenic rat model.
AB  - The aim of this investigation was to compare the effects of sodium fluoride (NaF)
      and parathyroid hormone (PTH) on ash density and strength in an osteopenic rat
      model. The study comprised 66 female virgin rats divided into the following 11
      groups, each comprising six animals: baseline controls; baseline ovariectomized
      (ovx); intact controls (5 and 16 weeks), ovx controls (5 and 16 weeks); ovx
      treated with PTH (0.02 mg/kg per day, 5 and 16 weeks); ovx treated with NaF (10
      mg/kg per day, 5 and 16 weeks); ovx-treated with NaF (1.0 mg/kg per day, 16
      weeks). Ovariectomy was performed at 12 weeks of age, 14 weeks prior to start of
      treatment. Ash density, bone fluoride content, and biomechanical analyses were
      performed on femoral cortical bone, the right femoral neck, and the sixth lumbar
      vertebral body. ovx had no effect on cortical bone, whereas the femoral neck
      displayed a significantly lower bone strength in ovx baseline animals compared
      with intact baseline rats (p < 0.05). Vertebral ash density was found to be
      significantly decreased in ovx rats after 5 and 16 weeks (p < 0.05). Treatment
      with fluoride had little effect on the osteopenic rat skeleton. Cortical ash
      density was significantly lower than ovx and intact groups in the high-dose
      treated rats after 5 (p < 0.01) but not after 16 weeks. High doses of fluoride
      for 16 weeks induced a significant increase in maximum load and normalized
      strength in cortical bone when compared with intact animals (p < 0.05), but not
      at the other bone sites. Cortical bone strength was not different from the ovx
      animals at either timepoint. In fluoride-treated animals, femoral neck bone
      strength, vertebral body bone strength, bone quality, and ash density were found
      to be at about ovx levels and, in the vertebral body, significantly lower than
      intact animals (p < 0.05, p < 0.01). In contrast, treatment with PTH increased
      ash density, bone strength, and bone quality to above ovx levels (p < 0.01), and
      above the level of the intact animals also, although significant values were
      reached for cortical bone strength only (p < 0.01). Additionally, biomechanical
      competence and ash density measurements were significantly higher in PTH-treated
      rats compared with fluoride-treated rats. In conclusion, this study has shown
      that PTH has a highly anabolic effect and is capable of effectively restoring ovx
      induced loss of bone mass and biomechanical competence. In addition, in this
      osteopenic rat model, PTH proved much more advantageous than treatment with
      fluoride, which failed to restore the ovx-induced loss of bone strength.

PMID- 9145242
TI  - Short-term effects of corticosteroids on trabecular bone remodeling in old ewes.
AB  - This study was an attempt to develop an animal model of steroid-induced low bone
      formation, potentially suitable for testing bone forming agents. The short-term
      effects of corticosteroids on bone remodeling were analyzed in ewes. One group of
      16 animals (mean age: 9 +/- 1 years) received a daily intramuscular injection of
      16 mg of methylprednisone (MP group) for 3 months. The other group of 16 animals
      was considered the control group. At the end of treatment, significant decreases
      of osteoblastic (-50%) and mineralizing (-64%) perimeters and wall width (-5%)
      were noted in the MP group. The bone formation rate at the tissue level was
      significantly decreased by 91%. In contrast, at the cell level, there was no
      reduction in the daily production of matrix by the osteoblasts: Aj.AR was 40%
      lower than in controls, but the difference was not significant. At the end of the
      treatment, a significant increase in eroded perimeter (+97%) was associated with
      a significant decrease of osteoclast number. Biochemical markers of bone
      formation (osteocalcin and bone-specific alkaline phosphatase) and urinary cAMP
      were unchanged. Due to the short duration of the treatment, neither bone volume
      nor microarchitecture parameters were modified. The decreases of both the
      activation frequency and osteoclast number associated with the increase in eroded
      surfaces suggest a prolongation of the reversal phase due to an inhibition of
      osteoblast differentiation. Changes of bone formation in ewes induced by short
      term administration of MP were similar to those reported after 3 months of
      treatment in humans. Thus, corticosteroid-treated ewes may represent a suitable
      animal model of low bone formation.

PMID- 9145243
TI  - Methotrexate maintains bone mass by preventing both a decrease in bone formation
      and an increase in bone resorption in adjuvant-induced arthritic rats.
AB  - We examined the effects of low doses methotrexate (MTX) and indomethacin (IND) on
      bone mass and turnover in normal male Sprague-Dawley rats and those with adjuvant
      induced arthritis. Normal and the adjuvant (heat-killed mycobacterium)-injected
      rats, 6 weeks of age, were given MTX at daily doses of 0.05, 0.1, or 0.2 mg/kg
      body weight (BW) or IND at a daily dose of 1.0 mg/kg BW. Rats were killed at the
      start, or at 14 and 28 days. In normal rats, the administration of these agents
      did not change the lumbar and femoral BMD values, nor did the serum osteocalcin
      or urinary deoxypyridinoline (D-Pyr) levels. Lumbar trabecular osteoclast number
      (Oc.N/BS) and osteoclast surface (Oc.S/BS) were decreased in the rats given IND.
      In the arthritic rats, the administration of MTX did not prevent an early
      increase of paw edema in the adjuvant-injected limb, but late inflammatory edema
      was alleviated in the non-injected limb. However, MTX administration at a dose of
      0.1-0.2 mg/kg BW maintained an age-dependent increase in the lumbar and femoral
      BMD values. While serum osteocalcin levels were decreased and urinary D-Pyr
      values were increased in the arthritic control rats, these bone markers remained
      at the levels of the normal rats. Decreases in mineral apposition rate (MAR) and
      bone formation rate (BFR/BS) and increases in the trabecular Oc.N/BS and Oc.S/BS
      values were prevented by MTX. While IND almost completely prevented inflammatory
      paw edema, it did not improve the parameters of bone formation. An increase in
      osteoclasts was prevented and the osteopenia in the lumbar and the femoral bone
      was only partially prevented by IND. These data suggest that MTX improves bone
      mass and turnover in the arthritic rat, in which several cytokines that affect
      bone cells are involved. An increase in bone resorption may be due to
      prostaglandins, but bone formation defect was suggested to be due to other
      cytokines such as IL-1, IL-6, and TNF-alpha in this model.

PMID- 9145244
TI  - Effects of an inhibitor of cathepsin L on bone resorption in
      thyroparathyroidectomized and ovariectomized rats.
AB  - The process of bone resorption by osteoclasts involves the dissolution of mineral
      salts and enzymatic degradation of the mainly collagenous extracellular matrix.
      Cysteine proteinases, which can efficiently degrade collagen at acidic pH, have
      been suggested to play an important role in the bone resorptive process. The
      cysteine proteinase cathepsin L is secreted by osteoclasts, and inhibitors of
      this enzyme can prevent bone resorption in vitro. The activity of acetyl-leu-leu
      norleucinol (ALLN), a selective inhibitor of cathepsin L, was investigated in two
      models of bone resorption in vivo. In the first study, the ability of ALLN to
      inhibit bone resorption was investigated in Ro-13-6298 (arotinoid)-treated
      thyroparathyroidectomized (TPTX) rats. ALLN [100 mg/kg, intraperitoneally (i.p.)]
      inhibited hypercalcemia by 62.8% acutely (p < 0.001), compared to 94.9% (p <
      0.001) inhibition by salmon calcitonin (sCT) (10 IU/kg, subcutaneously). In rats
      treated for 3 days with ALLN, arotinoid-induced reduction in cortical bone
      mineral density measured by peripheral quantitative computed tomography (pQCT)
      was inhibited by 86.4% (p < 0.05) in rats treated with ALLN 100 mg/kg, i.p., and
      by 82% in rats treated with 50 mg/kg, i.p. (p < 0.05). In a second study, the
      efficacy of ALLN was tested in a longitudinal study in ovariectomized (ovx) rats.
      Bone loss, measured by pQCT, was unaffected by treatment with ALLN. The
      bisphosphonate alendronate, however, inhibited bone loss in this model. These
      data demonstrate the ability of a cathepsin L inhibitor to inhibit bone
      resorption in arotinoid-treated TPTX rats, a process which may be dependent on
      the activity of cathepsin L-like cysteine proteinases. In contrast to its effects
      in TPTX rats, ALLN had no inhibitory activity on bone resorption in ovx rats. It
      is possible that in chronic bone resorption in ovx rats, the activity of other
      enzymes such as cathepsins OC-2 or K allows the process of resorption to continue
      even when cathepsin L is inhibited by ALLN. Further studies are required to
      determine why the activity of ALLN varies between different animal models. These
      data indicate that there may be variations in the effects of drugs in different
      animal models of bone resorption which should be considered when investigating
      novel antiresorptive therapies.

PMID- 9145245
TI  - Effect of antiandrogens casodex and epitestosterone on bone composition in mice.
AB  - Nonsteroidal antiandrogen casodex and steroidal antiandrogen epitestosterone were
      administered to intact male mice, and their effect on femoral bones and
      circulating calcium, phosphate, testosterone, and LH were compared with controls
      and castrated animals. Pure antiandrogen casodex in a dose used in humans for
      treatment of prostate cancer decreased the weight of seminal vesicles, organ
      which is highly sensitive to the androgenic effect, increased insignificantly the
      concentration of LH and of testosterone, but did not have any effect on bone
      density or mineral content of bone. Epitestosterone, which not only inhibits the
      binding of androgens to their receptors but also inhibits the formation of
      dihydrotestosterone from testosterone, and is reported to interfere with
      aromatization of testosterone to estrogens, decreased the bone density, ash
      weight, and calcium and phosphate content of femoral bone tissue significantly,
      although not to values as low as those seen in castrated animals.

PMID- 9145246
TI  - Bone mass and bone turnover in power athletes, endurance athletes, and controls:
      a 12-month longitudinal study.
AB  - Strain magnitude may be more important than the number of loading cycles in
      controlling bone adaptation to loading. To test this hypothesis, we performed a
      12 month longitudinal cohort study comparing bone mass and bone turnover in elite
      and subelite track and field athletes and less active controls. The cohort
      comprised 50 power athletes (sprinters, jumpers, hurdlers, multievent athletes;
      23 women, 27 men), 61 endurance athletes (middle-distance runners, distance
      runners; 30 women, 31 men), and 55 nonathlete controls (28 women, 27 men) aged 17
      26 years. Total bone mineral content (BMC), regional bone mineral density (BMD),
      and soft tissue composition were measured by dual-energy X-ray absorptiometry.
      Bone turnover was assessed by serum osteocalcin (human immunoradiometric assay)
      indicative of bone formation, and urinary pyridinium crosslinks (high-performance
      liquid chromatography) indicative of bone resorption. Questionnaires quantified
      menstrual, dietary and physical activity characteristics. Baseline results showed
      that power athletes had higher regional BMD at lower limb, lumbar spine, and
      upper limb sites compared with controls (p < 0.05). Endurance athletes had higher
      BMD than controls in lower limb sites only (p < 0.05). Maximal differences in BMD
      between athletes and controls were noted at sites loaded by exercise. Male and
      female power athletes had greater bone density at the lumbar spine than endurance
      athletes. Over the 12 months, both athletes and controls showed modest but
      significant increases in total body BMC and femur BMD (p < 0.001). Changes in
      bone density were independent of exercise status except at the lumbar spine. At
      this site, power athletes gained significantly more bone density than the other
      groups. Levels of bone formation were not elevated in athletes and levels of bone
      turnover were not predictive of subsequent changes in bone mass. Our results
      provide further support for the concept that bone response to mechanical loading
      depends upon the bone site and the mode of exercise.

PMID- 9145247
TI  - Determining mineral content variations in bone using backscattered electron
      imaging.
AB  - The mechanical properties of bones are greatly influenced by the ratio of organic
      constituents to mineral. Determination of bone mineral content on a macroscopic
      scale is straightforward, but microscopic variations, which can yield new
      insights into remodelling activities, mechanical strength, and integrity, are
      profoundly more difficult to measure. Measurement of microscopic mineral content
      variations in bone material has traditionally been performed using
      microradiography. Backscattered electron (BSE) imaging is a technique with
      significantly better resolution than microradiography with demonstrated
      consistency, and it does not suffer from projection-effect errors. We report
      results demonstrating the applicability of quantitative BSE imaging as a tool for
      measuring microscopic mineral content variations in bones representing a broad
      range of mineralization. Bones from ten species were analyzed with Fourier
      transformed infrared spectroscopy, X-ray diffraction, energy dispersive X-ray
      spectrometry, ash measurements, and BSE imaging. BSE image intensity (graylevel)
      had a very strong positive correlation to mineral (ash) content. Compositional
      and crystallographic variations among bones had negligible influence on
      backscattered electron graylevels. The present study confirms the use of BSE
      imaging as a tool to measure the microscopic mineral variability in a broad range
      of mineralized tissues.

PMID- 9145248
TI  - Loss of bone mineral of the hip assessed by DEXA following tibial shaft
      fractures.
AB  - We measured prospectively early changes (0-6 months) in bone mineral of the hip,
      the lumbar spine, and the tibia following tibial shaft fractures (n = 12), and in
      a cross-sectional study we evaluated the maximal amount of bone loss possible at
      the hip and tibia following long-term (average 3 years) impaired limb function as
      a consequence of complicated tibial shaft fractures [delayed union or nonunion (n
      = 7), chronic osteomyelitis (n = 5), decreased limb length (n = 1), or bone
      defect (n = 1)]. Bone mineral measurements were performed by dual energy X-ray
      absorptiometry. Following tibial shaft fractures, a significant decrease in bone
      mineral density (BMD) was seen at the hip reaching 7% [confidence limits (CL): 
      10.2%; -3.5%] and 14% (CL: -19.6; -7.8%) after 6 months for the femoral neck and
      greater trochanter, respectively. In the proximal tibia, bone mineral content
      (BMC) decreased and was 19% (CL: -27.4%; -9.9%) below the initial value after 6
      months. BMD of the lumbar spine remained unchanged. In the cross-sectional study,
      BMC in the tibia of the injured legs was 43% (CL: -53.2%; -31.9%) below the value
      in the healthy contralateral legs, and BMD in the femoral neck and greater
      trochanter, respectively, was 22% (CL: -27.4%; -17.6%) and 24% (CL: -36.3%; 
      12.1%) below the values in the healthy contralateral legs. With respect to the
      expected age-related decay of bone mineral after peak bone mass, the loss of bone
      mineral of the hip and tibia associated with tibial shaft fractures may be
      considered of clinical importance with increased risk of sustaining a fragility
      fracture of the lower extremity later in life; and the complicated fractures may
      even represent a present risk of fracture.

PMID- 9145249
TI  - The characterization of broadband ultrasound attenuation and fractal analysis by
      biomechanical properties.
AB  - The purpose of this study was to show how the difference in structure affects the
      mechanical properties of bone and if BUA or fractal analysis is able to detect
      these changes in mechanical properties. A total of 38 cancellous bone cubes were
      obtained from seven bovine tibiae (32 specimens) and one human tibia (6
      specimens). BUA was measured in the superior/inferior (SI), medial/lateral (ML),
      and anterior/posterior (AP) directions for each specimen. The fractal dimension
      was estimated by using the continuous alternating sequential filter (CASF)
      pyramid approach to handle fractal dimension estimation of small images.
      Nondestructive compressive tests were also performed in the three orthogonal
      directions for each sample. The correlations between BUA and density were
      statistically significant for all three directions. The correlation between BUA
      and elastic modulus varied depending on the direction in which the two parameters
      were measured. The best correlation was in the AP directions (r = 0.75, p <
      0.0001), followed by the ML direction (r = 0.52, p = 0.0006), and finally the SI
      direction (r = 0.18, p = 0.28). The only significant correlation between fractal
      dimension and density was in the SI direction (r = 0.39, p = 0.015). There was
      significant correlation between fractal dimension and elastic modulus in all
      three directions, but the direction that exhibited the best correlation was the
      SI direction (r = 0.61, p < 0.0001). The correlation coefficients for the AP and
      ML directions were 0.45 (p = 0.0046) and 0.34 (p = 0.0377), respectively. A
      multivariate model, carried out to predict the elastic modulus from the BUA or
      fractal dimension including density, demonstrated that the correlation
      coefficient significantly increased in all three directions for BUA and fractal
      dimension. After adjustment for density, significant relationships between
      elastic modulus and BUA or fractal dimension were still found (p < 0.05).

PMID- 9145250
TI  - Paget's disease.

PMID- 9145251
TI  - Do behavior changes herald physical illness in adults with mental retardation?
AB  - A longitudinal study of 62 individuals with profound mental retardation was
      conducted to determine if direct care staff can identify behavior change prior to
      identifying symptoms of acute illness. Results indicate that staff were able to
      notice changes in sluggishness prior to the onset of illness. Self-care behavior
      was of borderline significance and there was no significant change in eight
      behavior dimensions (vocalizations, peer conflict, stereotypy, aggression, self
      injurious behavior, restlessness, distractibility, and depression). This finding
      should alert physicians and caregivers to the importance of prompt response to
      symptoms. Reliance on behavioral observation of direct care staff is not always
      sensitive enough to pick up changes in health status in less restrictive
      residential environments.

PMID- 9145252
TI  - Prediction of vocational outcome based on clinical and demographic indicators
      among vocationally ready clients.
AB  - This study examined the clinical and demographic correlates of work skills and
      vocational outcome for persons with psychiatric disabilities. The same clinical,
      demographic, work skills, and vocational outcome instruments were administered to
      275 persons working toward their vocational goals at three psychosocial
      rehabilitation centers. Data regarding vocational outcomes were collected
      quarterly over a period of 3 1/4 years. Using multivariate statistical
      techniques, clinical and demographic variables that predict work skills and
      future vocational outcomes were identified. The implications of the findings for
      program administrators, system planners, and researchers are discussed.

PMID- 9145253
TI  - Impact of assertive community treatment on homeless persons with co-occurring
      severe psychiatric and substance use disorders.
AB  - This study evaluated the impact of an integrated (mental health/substance abuse)
      assertive community treatment program on homeless persons with serious mental and
      substance use disorders. High rates of retention in treatment, housing stability,
      and community tenure were attained, and all but the most severe substance users
      appeared to gain these benefits. While the intervention appears to be an
      effective means of retaining in services and monitoring such difficult-to-treat
      and costly populations, it did not yield high rates of abstinence and social
      benefits in severe users.

PMID- 9145254
TI  - Consumer satisfaction with CMHC services.
AB  - To examine the relationship between consumer satisfaction with community mental
      health clinic (CMHC) services and patterns of outpatient service use, we
      conducted a survey of 210 schizophrenics in Mississippi, the majority of whom
      were African American. Subjects with lowest CMHC satisfaction were those who did
      not identify the CMHC as their primary source of outpatient mental health care.
      They were more likely to be white, single, and to either receive no outpatient
      mental health care (46%) or to seek care from sources other than the CMHC (54%),
      many of which might provide substandard care, such as family doctors, ministers,
      folk healers, or hospital emergency rooms. Among those who identified the CMHC as
      their primary source of mental health care, we found little evidence that
      satisfaction was associated with type, variety, or frequency of services. Even
      though clinics offered similar services, there were differences in consumer
      satisfaction ratings by clinics, suggesting that qualities of the clinic itself
      may influence consumer satisfaction.

PMID- 9145255
TI  - Behavioral risk for HIV infection among adults with a severe and persistent
      mental illness: patterns and psychological antecedents.
AB  - Behaviors associated with transmission of the human immunodeficiency virus (HIV)
      were measured in a sample of 60 adults with a severe and persistent mental
      illness (SPMI). Results revealed that 68% had sex in the last year; 13% of men
      and 30% of women reported two or more male partners, and 24% of men also reported
      two or more female partners. Condom use was inconsistent. Sex partners were often
      met in a psychiatric clinic or bar, and a substantial number were injection drug
      users or known to be non-monogamous. Overall, 48% of men and 37% of women
      reported at least one risk factor. Hypothesized psychological antecedents of HIV
      related risk behavior were also measured, including knowledge, motivation for
      risk reduction, and self-efficacy regarding risk-reduction. Many participants
      were misinformed regarding HIV-transmission and risk reduction. Motivational
      indices indicated that attitudes toward condoms were slightly positive, and that
      social norms were generally supportive of condom use. However, participants
      tended to rate themselves at only slight risk for infection, undermining their
      motivation for condom use. Participants indicated only modest levels of self
      efficacy in situations requiring sexual assertiveness. These findings, coupled
      with the elevated seroprevalence of HIV among persons having a SPMI, point to the
      need for risk assessment and counseling by mental health care providers.

PMID- 9145256
TI  - How mental health and developmental disabilities staff prioritize training and
      development needs.
AB  - This paper contrasts a staff training needs assessment distributed to three
      groups: staff serving persons with mental health needs in the community, staff
      serving persons with mental health needs in state hospitals, and staff serving
      persons with developmental disabilities in the community. Analyses revealed that
      all three groups rated team-related training as the area in greatest need of
      development. Further analyses suggested that community staff serving persons with
      developmental disabilities reported significantly less need for training on
      direct client care compared to community and inpatient staff who serve persons
      with mental health needs. The community staff serving persons with mental health
      needs did not differ significantly from the inpatient staff on any of the
      surveyed training areas. Results suggest that future development efforts should
      begin with team building skills.

PMID- 9145257
TI  - A home-based program for the treatment of acute psychosis.
AB  - There is evidence that home treatment is an effective alternative to hospital
      admission for patients with acute psychiatric illnesses. This report describes
      processes necessary to establish and disseminate home treatment programs as well
      as the impact and comparative cost of a home treatment program developed in
      Metropolitan Toronto. Organizational analysis revealed a number of essential
      structures and interactions necessary to facilitate smooth functioning for home
      treatment programs involving several agencies. Attitudes towards home treatment
      were positive, symptoms were reduced, family burden decreased, satisfaction was
      high and home treatment was preferred to hospital admission. Economic data
      indicate that home treatment is less costly than hospitalization.

PMID- 9145258
TI  - Proposal for a revised international standard series of patch tests.
AB  - Worldwide, there are 3 major standard series of patch tests, the European, North
      American and Japanese, together presenting 32 allergens, the differences between
      them being the result of regional variation in allergen distribution as well as
      differences in dermatological opinion. We propose a "minimal" international
      standard series of 20 allergens, together with an "extended" international
      standard series of 14 allergens.

PMID- 9145259
TI  - Contact reactions to the jellyfish Carybdea marsupialis: observation of 40 cases.

PMID- 9145260
TI  - Patch testing to detect corticosteroid allergy: is it adequate?
AB  - Whilst patch testing with corticosteroids in ethanol is more sensitive than
      either petrolatum or the cream formulation, the frequency of false-negative
      reactions is not known. We have compared patch testing with corticosteroid at 1%
      in ethanol with intradermal (i.d.) tests using 1 mg corticosteroid suspended in
      normal saline. Patch tests with tixocortol pivalate and budesonide detected all
      patients allergic to hydrocortisone and budesonide, respectively. For other
      corticosteroids, the use of ethanol as a vehicle resulted in both false-positive
      and false-negative reactions. In particular, patch tests with hydrocortisone-17
      butyrate missed 30% of all positive reactions detected by i.d. testing. There may
      be a case for advising the avoidance of this steroid in all patients who are
      positive on patch testing to tixocortol pivalate and budesonide.

PMID- 9145261
TI  - 1,2-Benzisothiazolin-3-one (Proxel): irritant or allergen? A clinical study and
      literature review.
AB  - The isothiazolinone, 1,2-benzisothiazolin-3-one (Proxel), is a popular
      preservative, as well as a skin sensitizer and irritant. Patch test studies have
      been performed with different concentrations and vehicles. The current suggested
      patch test concentration is 0.1% BIT in petrolatum (pet). This article evaluates
      the effects of patch testing at this concentration and reviews the current
      literature. An irritancy patch test was performed on 56 controls, using BIT in
      concentrations of 0.002% and 0.05% in aqueous dipropylene glycol (Proxel GXL) and
      0.1% in pet. 10 had positive readings at 4 days with 0.1% BIT in petrolatum, 9 of
      which were negative at retest. 0.1% BIT is, therefore, irritant and not a
      suitable concentration for patch testing. Literature review revealed 15 patch
      test studies, with varying testing techniques. Additional studies with adequate
      controls and experimental tests should be invaluable in furthering our insight
      into BIT sensitization and irritation.

PMID- 9145262
TI  - Hand dermatitis and allergic patch test reactions caused by nickel in
      electroplaters.
AB  - A worksite survey was conducted in all 38 Finnish electroplating plants. All
      workers (n = 163) who worked with nickel plating (bath workers, hangers and
      solution makers) were interviewed with a questionnaire about symptoms of nickel
      dermatitis, hand dermatitis, and about protective measures, atopy, etc. Patch
      testing with nickel sulfate was done with the TRUE TestTM method. All the
      workers, 94 men and 69 women, answered the questionnaire. The mean age of women
      was 41.1 years, and of men 43.1 years, respectively. Men had longer occupational
      exposure to nickel (14 years) than women (10 years). Most workers used protective
      gloves. 35% of women and 30% of men reported present or past hand dermatosis. 19%
      reported a history of atopic dermatitis. 15% of women (n = 8) and 4% (n = 2) of
      men had an allergic patch test reaction to nickel sulfate. 70% of those with an
      allergic patch test reaction to nickel reported past or present hand eczema. The
      prevalence of nickel allergy among the electroplaters was similar to that of
      patients in patch test clinics in Finland. An allergic patch test reaction to
      nickel sulfate does not necessarily oblige an electroplater to change jobs.

PMID- 9145263
TI  - Contact allergy to dental restorative materials in patients with oral lichenoid
      lesions.
AB  - 118 patients with oral lichenoid lesions (OLL) topographically related to dental
      fillings were patch tested (PT) to reveal contact allergy to restorative
      materials. 80 (67.8%) patients displayed positive PT reactions to metals of
      dental filling materials: 76 reactions were found to various mercury compounds, 4
      to sodium aurothiosulphate, 3 to stannic chloride and 2 to silver nitrate. The
      positive patch test reactions appeared more commonly in patients with restricted
      contact lesions (85.1%, type-1 lesions) as compared to patients with lesions
      exceeding to the adjacent areas (38.6%, type-2 lesions). The replacement of
      dental fillings was carried out in 62/80 PT-positive and 15/38 PT-negative
      patients. 28 out of 62 (45.2%) PT-positive and 3/15 (20%) PT-negative patients
      showed complete healing of OLL after a mean follow-up time of 16 months. Complete
      healing occurred in 29/54 (54.0%) type-1 and 2/23 (8.7%) type-2 lesions.
      Topographical relation between the lesion and the filling material (restricted
      versus exceeding the contact area) indicated association of OLL lesion and the
      filling material, which could be further confirmed by patch testing in the
      majority of patients. The patch test series should include mercuric chloride
      (0.1%), mercury (0.5%) and mercury ammonium chloride (1.0%), each in pet.

PMID- 9145264
TI  - Skin reactions to hydroxyzine.
AB  - Sensitivity to histamine H1-antagonists has mainly been observed with
      phenothiazine and ethylenediamine, and is very rare with hydroxyzine. We report 3
      cases of sensitization to hydroxyzine, which was prescribed to treat urticaria
      and atopic dermatitis. A generalized maculopapular eruption appeared shortly
      after taking the drug. Patch tests with Atarax tablet were positive +3, and +2 or
      +3 with different dilutions of hydroxyzine. Patch tests with ethylenediamine,
      piperazine and other antihistamines were negative; therefore, there is no cross
      allergy. We believe these rapid systemic reactions to hydroxyzine after the
      initial dose may have been due to prior systemic sensitivity to this drug, which
      cannot be used topically. Allergy to antihistamines must be considered when
      cutaneous lesions worsen on such therapy.

PMID- 9145265
TI  - Discrepancy in patch test results with wool wax alcohols and Amerchol L-101.
AB  - Wondering why Amerchol L-101 (containing wool wax alcohols obtained from the
      hydrolysis of wool fat) appears as a test material (100%) in a cosmetics series
      (Chemotechnique Diagnostics AB), as wool wax alcohols were already tested in the
      European standard series, we added Amerchol L-101 (100%) systematically to the
      standard series. From 8 April 1991 to 28 February 1992, a total of 393 patients
      were tested: 3.05% (n = 12) showed positive test results (+, +2, +3) for wool wax
      alcohols as well as Amerchol L-101 (100%), 0.3% (n = 1) for wool wax alcohols
      only, and 11.1% (n = 44) for Amerchol L-101 (100%) only. Thus, the positive tests
      for Amerchol L-101 (100%) had a higher frequency of 3.4 compared to those for
      wool wax alcohols. In the meantime, we also added Amerchol L-101 50% (Trolab) to
      the standard series. Of all patients tested (n = 223) 2.7% (n = 6) had positive
      reactions to wool wax alcohols and 12.1% (n = 27) to Amerchol L-101 100% and/or
      50%. Thus, positive reactions to Amerchol L-101 (100% and 50%) were 4.5 higher,
      whereas the rate of concordancy decreased. It is remarkable that 8 patients only
      had a positive reaction to Amerchol L-101 50% and 9 only to Amerchol L-101 100%.
      It seems that we miss many diagnoses in contact allergy by using only the
      standard wool wax alcohols test (30%).

PMID- 9145266
TI  - pH measurements during lactic acid stinging test in normal and sensitive skin.
AB  - Because of the lack of objective signs, the phenomenon of sensitive skin is hard
      to document. The measurement of the skin pH variations in the nasolabial fold,
      and on the forearm, after a single application of lactic acid on a preselected
      sensitive skin population, versus a control one, is proposed as a useful test to
      detect this kind of population.

PMID- 9145267
TI  - Iodopropynyl butylcarbamate: a new contact allergen.
AB  - Iodopropynyl butylcarbamate (IPBC) has been used for years as a fungicide and
      bactericide for wood and paint preservation without any reports of cutaneous side
      effects. During the last few years, it has entered cosmetic products and is
      temporarily permitted in the EU Cosmetics Directive in a use concentration of
      0.1%. In the present study, we report our preliminary experience with patch
      testing consecutive contact dermatitis patients with IPBC. A patch test
      concentration of 0.1% seems appropriate for initial screening but deserves
      further evaluation. Among 311 consecutive patch test patients, 3 patients with a
      positive patch test to IPBC have been identified. Contact allergy is likely in at
      least 1 case, based on clinical history, exposure history, patch testing with
      dilution series, ROAT and chemical analysis.

PMID- 9145268
TI  - Non-eczematous urticarioid allergic contact dermatitis due to Eumulgin L in a
      deodorant.

PMID- 9145269
TI  - Contact dermatitis from sodium-cromoglycate-containing eyedrops.

PMID- 9145270
TI  - Hydroxylammonium chloride as sensitizer in a water laboratory.

PMID- 9145271
TI  - Occupational protein contact dermatitis in a fishmonger.

PMID- 9145272
TI  - Product analysis of acrylic resins compared to information given in material
      safety data sheets.

PMID- 9145273
TI  - Allergic contact dermatitis from mono-, di- and triethanolamine.

PMID- 9145274
TI  - Contact dermatitis from diphenylthiourea in a knee brace.

PMID- 9145275
TI  - Lymphocytoma cutis involving the lower lip.

PMID- 9145276
TI  - Chemical burn from acetic acid with deep ulceration.

PMID- 9145277
TI  - No evidence of cross-reaction between fepradinol and other phenylethanolamines.

PMID- 9145278
TI  - Allergic contact dermatitis from colophony in lipsticks.

PMID- 9145279
TI  - Allergic contact dermatitis due to diethyl sebacate.

PMID- 9145280
TI  - Vesicular dermatitis of the hands secondary to perianal allergic contact
      dermatitis caused by preservatives in moistened toilet tissues.

PMID- 9145281
TI  - Contact sensitivity in women with anogenital dermatoses.

PMID- 9145282
TI  - Photosensitivity due to actarit.

PMID- 9145283
TI  - Cutaneous reaction to cosmetic lip tattooing.

PMID- 9145284
TI  - Allergic contact dermatitis from apomorphine.

PMID- 9145285
TI  - Photocross-linking of nucleic acids to associated proteins.
AB  - Photocross-linking is a useful technique for the partial definition of the
      nucleic acid-protein interface of nucleoprotein complexes. It can be accomplished
      by one or two photon excitations of wild-type nucleoprotein complexes or by one
      photon excitation of nucleoprotein complexes bearing one or more substitutions
      with photoreactive chromophores. Chromophores that have been incorporated into
      nucleic acids for this purpose include aryl azides, 5-azidouracil, 8
      azidoadenine, 8-azidoguanine, 4-thiouracil, 5-bromouracil, 5-iodouracil, and 5
      iodocytosine. The various techniques and chromophores are described and compared,
      with attention to the photochemical mechanism.

PMID- 9145286
TI  - The family of the small leucine-rich proteoglycans: key regulators of matrix
      assembly and cellular growth.
AB  - The focus of this review is on conceptual and functional advances in our
      understanding of the small leucine-rich proteoglycans. These molecules belong to
      an expanding gene class whose distinctive feature is a structural motif, called
      the leucine-rich repeat, found in an increasing number of intracellular and
      extracellular proteins with diverse biological attributes. Three-dimensional
      modeling of their prototype protein core proposes a flexible, arch-shaped binding
      surface suitable for strong and distinctive interactions with ligand proteins.
      Changes in the properties of individual proteoglycans derive from amino acid
      substitutions in the less conserved surface residues, changes in the number and
      length of the leucine-rich repeats, and/or variation in glycosylation. These
      proteoglycans are tissue organizers, orienting and ordering collagen fibrils
      during ontogeny and in pathological processes such as wound healing, tissue
      repair, and tumor stroma formation. These properties are rooted in their
      bifunctional character: the protein moiety binding collagen fibrils at strategic
      loci, the microscopic gaps between staggered fibrils, and the highly charged
      glycosaminoglycans extending out to regulate interfibrillar distances and thereby
      establishing the exact topology of fibrillar collagens in tissues. These
      proteoglycans also interact with soluble growth factors, modulate their
      functional activity, and bind to cell surface receptors. The latter interaction
      affects cell cycle progression in a variety of cellular systems and could explain
      the purported changes in the expression of these gene products around the
      invasive neoplastic cells and in regenerating tissues.

PMID- 9145287
TI  - Bronchopulmonary dysplasia in the 1990s: a review for the pediatrician.

PMID- 9145288
TI  - Restoration of disturbed tooth eruption in osteopetrotic (op/op) mice by
      injection of macrophage colony-stimulating factor.
AB  - Osteopetrotic (op/op) mice show severe osteosclerosis caused by an inherited
      deficiency of osteoclast and resultant failure of tooth eruption, which can be
      cured by the injection of macrophage colony-stimulating factor (M-CSF). The
      present study revealed that consecutive injections of M-CSF in these mutant mice
      brought about a recovery of bone resorption resulting in the resumption of growth
      of tooth root and periodontal ligament. Bone resorption at the inner surface of
      bony crypts was noted on the 5th day after the start of M-CSF injections. This
      activity was reduced with the progress of root and periodontal ligament
      formation, being confined to the basal and crestal portion of bony crypts by the
      15th day of the experiment. Second molars emerged into the oral cavity on the
      15th day, but no eruption of first molars was observed until the 20th day.
      Throughout the experiment, first molars exhibited appreciable root deformity,
      which was less severe in second molars. Delayed eruption of first molars was
      thought to be related to the severity of the disturbance of root formation.

PMID- 9145289
TI  - Correlation of mast cells with spindle cell hyperplasia in the adrenal cortex of
      IQI/Jic mice.
AB  - IQI/Jic mice showed a high incidence of subcapsular spindle cell hyperplasia
      (SCH) in the adrenal cortex accompanied by prominent mast cell infiltration. SCH
      positive animals appeared as early as at 3 months of age, with an incidence of
      18% in males and 20% in females. Except for one mouse, all females older than 6
      months had the lesion. In males, the incidence increased gradually until 9
      months, and was then stable at 75-88% thereafter. The severity of SCH increased
      with age in both sexes, and the lesions were more prominent in females. Mast
      cells infiltrated mainly at the sites of spindle cell hyperplasia, and their
      density was associated with the severity on the lesion. A quantitative
      morphometric study confirmed a significant correlation between the severity of
      SCH and the density of mast cells. A histochemical study demonstrated that these
      mast cells were of the connective tissue-type. These observations indicate that
      IQI/Jic mice may be a useful strain to elucidate the pathogenesis of SCH in the
      adrenal cortex in association with mast cell function.

PMID- 9145290
TI  - Viability of transgenic rat embryos after freezing and thawing.
AB  - In-vivo viability of frozen-thawed embryos derived from transgenic rats, as well
      as the transmission and the expression of transgenes in the resultant newborn
      rats, was investigated. Three strains of transgenic rats, carrying human growth
      hormone gene connected downstream to the promoter region of the bovine alpha
      lactalbumin gene (alpha LA/hGH), bovine beta-casein gene (beta CN/hGH) or bovine
      alpha-S1 casein gene (alpha S1CN/hGH), were used. Two-cell stage embryos (non
      transgenic Wistar female x heterozygous transgenic male) were placed in 10% (v/v)
      dimethylsulfoxide (DMSO) solution and cooled from -7 to -30 degrees C at -0.5
      degree C/min before being plunged into liquid nitrogen. After 2 to 4 years
      storage, the embryos were thawed by rapid warming. The intact embryos were
      transferred into the oviducts of Day 1 pseudopregnant recipients. The postthaw
      survival rate of frozen embryos was high in all 3 transgenic strains (88 to 92%),
      which was similar to that of control (non-transgenic) frozen embryos (95%).
      Development to newborn rats following transfer of embryos derived from the 3
      strains (64 to 68%) was also similar to that of control embryos (60%). These
      transgenes (alpha LA/hGH, beta CN/hGH and alpha S1CN/hGH) were detected in the
      DNA extracts from tail tissue of the newborn rats, but the transmission rates
      (41, 23 and 32%, respectively) were lower than 50% which is expected in the
      Mendelian fashion. In a transgenic line carrying alpha S1CN/hGH, hGH levels of
      secretion into the milk of transgenic newborn rats derived from frozen-thawed
      embryos and her transgenic offspring were the same mg/ml-level as that of their
      founder rat. Two-step freezing of embryos derived from transgenic rats was
      therefore an effective method for the long-term cryopreservation of transgene.

PMID- 9145291
TI  - Process of the development of T-2 toxin-induced apoptosis in the lymphoid organs
      of mice.
AB  - Female ICR:CD-1 mice orally treated with 10 mg/kg b.w. of T-2 toxin were killed
      at 1, 3, 6, 9, 12, 24 and 48 hr after treatment (HAT) and subjected to
      examination of the process of the development of T-2 toxin-induced apoptosis in
      the thymus and spleen. The early ultrastructural changes in lymphocytes
      characterized by shrinkage of the cell body and condensation of nuclear chromatin
      were detected at 3HAT in the thymus. The number of apoptotic lymphocytes observed
      by the in situ detection method for fragmented DNA increased drastically from 9
      to 24 HAT in the thymus while it began to increase at 12 HAT in the spleen. The
      DNA ladder was first detected by agarose gel electrophoresis at 9 HAT and became
      clearer at 12 and 24 HAT in the thymus but was not clearly detected in the spleen
      throughout the observation period. Thus T-2 toxin-induced apoptosis developed
      earlier and was apparently severer in the thymus than in the spleen. Apoptotic
      was first detected by electron microscopy, then by the in situ detection method
      for fragmented DNA, and finally by DNA agarose gel electrophoresis.

PMID- 9145292
TI  - Histological characteristics of respiratory system in Brown Norway rat.
AB  - It is well known that the Brown Norway (BN) rat strain exhibits airway
      hyperresponsiveness to exposure to allergens or some chemicals. We investigated
      the histological characteristics of the trachea and lungs of this strain (10-week
      old and retired animals) and compared them with those of age-matched Fischer 344
      (F344) rat strain. No histological differences between two strains in tracheal
      epithelial cells were detected, but differences in the distribution and
      development of submucosal glands were clarified by the observation of serial
      sections cut at intervals of 100 microns. Submucosal glands of BN strain were
      larger in the number and better-developed than those of F344 strain, especially
      in the middle and lower trachea. Similar results were also obtained in scanning
      electron microscopic observation of resin casts. There were no significant
      differences between two strains in the lectin histochemical characteristics of
      the cytoplasm of glandular epithelial cells. No age-related changes in these
      morphological characteristics in the two strains were observed. These results
      suggest that mucin from submucosal glands is quantitatively different but
      qualitatively similar in the two strains. In addition, microgranuloma mainly
      composed of histiocytes and eosinophils was observed in the lungs of the BN
      strain rats.

PMID- 9145293
TI  - Relation between stable glycated hemoglobin A1C and plasma glucose levels in
      diabetes-model mice.
AB  - In an IDDM model mouse which was inoculated with a diabetogenic variant, DK-27,
      of encephalomyocarditis (EMC) virus, the relation between a stable glycated
      hemoglobin A1C (St-HbA1C) level and plasma glucose level (PGL) in the progress of
      diabetes was studied. The St-HbA1C level and PGL were examined every 2 weeks for
      10 weeks in normal male DBA/2 and IDDM-onset mice. PGLs of normal control mice
      did not change, but their St-HbA1C levels were slightly increased by 0.52 to
      1.03%. On the other hand, in IDDM mice, their PGLs were greatly increased (> 400
      mg/dl) and hyperglycemia was maintained throughout this observation period, with
      their St-HbA1C noticeably increased to 3.8% according to the progress of diabetes
      for 10 weeks. A highly significant correlation between St-HbA1C levels and
      averaged PGLs for the past weeks was found in IDDM mice. To examine the
      reflection of St-HbA1C levels to delicately varied PGLs, we also estimated both
      values in IDDM mice which were treated with insulin at a minimal effective dose
      once a day for 4 weeks. The St-HbA1C levels in insulin-injected IDDM mice were
      significantly lower than those in control IDDM mice. These findings suggest that
      the estimation of the St-HbA1C level is useful in following up blood glucose
      control in a long-term therapeutical study with small laboratory animals.

PMID- 9145294
TI  - Little or no response to 24-hr water-deprivation of Fos-like immunoreactivity in
      vasopressinergic magnocellular neurons in the hypothalamus of hereditary
      microphthalmic rats.
AB  - In normal rats, 24-hr water-deprivation was found to cause a significant increase
      in the plasma concentration of arginine vasopressin (AVP), and marked induction
      of Fos in the AVP-positive magnocellular neurons in the paraventricular nucleus
      (PVN) and the supraoptic nucleus (SON) of the hypothalamus. On the other hand, 24
      hr water-deprivation also caused a significant increase in the plasma AVP
      concentration in hereditary microphthalmic rats, but much less than in normal
      rats. Consistent with this, the extent of induction of Fos in the nuclei of the
      PVN and SON of these rats was lesser than in normal rats. These results suggest
      that hereditary microphthalmic rats have a defect or decrease in the response to
      water-deprivation of vasopressinergic magnocellular neurons in the PVN and SON.

PMID- 9145295
TI  - Hydrogen peroxide-induced dermatitis in WBN/Kob-Ht rats.
AB  - Light and electron microscopic examinations were carried out on the dorsal skin
      to which hydrogen peroxide (HPO) (3, 6, and 10%) was topically applied for 7
      consecutive days in Wistar rat-derived inbred WBN/Kob-Ht rats which have an
      autosomal dominant gene responsible for their characteristics of hypotrichosis.
      In addition to focal epidermal thickening, keratinocyte necrosis, dermal
      mononuclear cell infiltration and focal detachment of the epidermis from the
      dermis by fluid-filled spaces were detected. This is thought to be brought about
      by edema due to prominent capillary endothelial damage in the superficial dermis.
      The damage to keratinocytes and capillary endothelial cells was thought to be
      induced by HPO itself and free radicals generated by HPO. In addition, these
      changes were apparently more severe in WBN/Kob-Ht rats than in Wistar rats used
      as controls.

PMID- 9145296
TI  - Chemotherapeutic profiles of human tumors implanted in SCID mice showing
      appreciable inconsistencies with those in nude mice.
AB  - Sensitivities to antitumor drugs of human tumor xenografts (HTXs) implanted in
      C.B-17-scid and in BALB/cA-nu were compared to examine whether genetic
      backgrounds of immune deficiency of the host mice influenced the chemotherapeutic
      profiles of implanted tumors. In a total of 25 pairs of corresponding experiments
      with each host mouse strain (5 HTXs x 5 drug treatment groups), we obtained
      consistent results in 23 (92.0%) experiments consisting of 10 which were both
      significantly effective and 13 which were both ineffective, although the
      remaining two (8.0%) experiments showed inconsistent results. A human T-cell
      lymphoma cell line, LM-2-JCK, implanted in nude mice, was resistant to treatment
      with 65 mg/kg of cyclophosphamide, but this tumor showed sensitivity to the same
      treatment when implanted in either SCID mice or mice with a recombination
      activating gene 2 defect [BALB/cA-TgH (Rag2)], suggesting that the genetic immune
      background of the host mouse should not be overlooked as a factor affecting
      tumors.

PMID- 9145297
TI  - Plasma progesterone concentrations during pregnancy and lactation in Mongolian
      gerbils (Meriones unguiculatus).
AB  - Plasma progesterone (P4) concentrations during pregnancy and lactation in
      Mongolian gerbils were measured by enzymeimmunoassay (EIA). The P4 concentration
      was found to increase rapidly after mating and reach a peak on day 6 of
      pregnancy. The maximum level (166.0 to 184.8 ng/ml) was maintained to day 12 and
      then decreased to a plateau at a moderate level until day 21. The P4
      concentration declined to its lowest level on day 24 of pregnancy, one day before
      parturition. The P4 concentration on the first day of lactation was similar to
      that on the last day of pregnancy. The concentration then increased to a
      significantly higher level on day 4 of lactation, remained relatively stable
      until day 19, and then significantly dropped on day 22. The present study in
      gerbils showed that the plasma P4 concentration during pregnancy was higher in
      the first half than in the second half of gestation and that the P4 level during
      lactation was fairly constant. The pattern of changes in the P4 level during
      pregnancy and lactation is therefore quite different from that of other rodent
      species, such as rats, mice and hamsters.

PMID- 9145298
TI  - Quarantine for contaminated pathogens in transplantable human tumors or
      infections in tumor bearing mice.
AB  - To quarantine human tumor samples for transplantation into immune deficient mice
      or tumor xenograft lines established and introduced from other institutions, we
      performed isolated implantation and passaging of tumors in a vinyl isolator, and
      microbiological examinations of sentinel mice kept together with tumor bearing
      mice. We examined 105 pairs of sentinel mice used to quarantine 907 tumors, and
      found six cases of contamination or infection with Staphylococcus aureus, 20
      cases with Pseudomonas aeruginosa and one case with mouse hepatitis virus (MHV).
      It was, however, possible that Mycoplasma pulmonis contamination was overlooked
      because the microbe had been isolated from tumors passaged after quarantine, even
      though the results of the quarantine of these tumors showed no sign of pathogens.
      Direct culture of tumors for the microbe was recommended to improve the
      quarantine system.

PMID- 9145299
TI  - Pathological evaluation of effect of anti-rheumatic drugs on type II collagen
      induced arthritis in Lewis rats.
AB  - The effects of anti-rheumatic drugs (dexamethasone 0.1 mg/kg and naproxen 5
      mg/kg) were evaluated immunologically and histopathologically on type II collagen
      induced arthritis in Lewis rats. Increased paw volume in the hind limbs was
      significantly suppressed in the groups treated with dexamethasone or naproxen,
      but noticeable retardation of body weight gain was observed in the group treated
      with dexamethasone. Serum anti-type II collagen IgG was significantly suppressed
      in the group treated with dexamethasone but not naproxen. Histopathological
      evaluation by our grading system, classification of the stages in arthritic
      lesion development, revealed suppression of the inflammatory changes in the
      tarsal joints of the animals treated with dexamethasone or naproxen. From our
      results, histopathological evaluation is considered to be more suitable for
      assessment of the efficacy of anti-rheumatic drugs on type II collagen-induced
      arthritis, an animal model for human rheumatoid arthritis.

PMID- 9145300
TI  - Neuronal regulation of astrocyte morphology in vitro is mediated by GABAergic
      signaling.
AB  - The addition of isolated neurons to monolayers of cultured astrocytes induced a
      morphological change in the astrocytes that came into contact with the added
      neuronal cell bodies or neurites. The change, which included an increase in the
      complexity of cell shape, took at least 3 days to become detectable and was
      enhanced in proportion to the number of attached neurons. Astrocytes that did not
      make contact with any neurons had a less complex contour, comparable to those in
      control cultures with no neurons added. Treatment of neuron-astrocyte cocultures
      with a sodium channel blocker, tetrodotoxin, suppressed the neuron-induced
      morphological changes in astrocytes. A GABAA-receptor antagonist, bicuculline,
      mimicked the inhibitory effect of tetrodotoxin. In cultures without added
      neurons, morphological alteration of astrocytes was also observed when cultures
      were incubated for 1 or more days with exogenous GABA together with a GABA-uptake
      inhibitor, 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol. The effect of
      exogenous GABA was mimicked by treatment with a GABAA-receptor agonist, muscimol,
      and blocked by bicuculline treatment. These results suggest that GABA released
      from neurons with their activity serves as a signal from neurons to astrocytes
      that triggers the morphological change in astrocytes through the activation of
      GABAA receptors.

PMID- 9145301
TI  - Asymmetric gap junctional coupling between glial cells in the rat retina.
AB  - Gap junctional communication between glial cells is thought to play a role in K+
      spatial buffering, in the propagation of inter-astrocytic Ca2+ waves, and in
      glial-neuronal signaling. In the present study, we characterize dye coupling
      between astrocytes, and between astrocytes and Muller cells, in the isolated rat
      retina. Whole-cell patch recordings were obtained from retinal astrocytes and
      Muller cells and the cells filled with Lucifer Yellow and neurobiotin. Spread of
      Lucifer Yellow to two to ten neighboring astrocytes occurred in 90% of the
      astrocyte recordings. After fixation and incubation of the retina with
      fluorescent conjugated streptavidin, neurobiotin was seen to label clusters of 13
      88 astrocytes, as well as > 100 Muller cells. In contrast, when Muller cells were
      filled with Lucifer Yellow and neurobiotin, both tracers were confined solely to
      the recorded Muller cell. The uncoupling agents octanol, halothane, and doxyl
      stearic acid were tested for their ability to uncouple retinal glia in situ. All
      three agents eliminated the visible spread of Lucifer Yellow from the injected
      astrocyte and the spread of neurobiotin into Muller cells. However, only doxyl
      stearic acid combined with octanol eliminated the spread of neurobiotin between
      astrocytes. These results demonstrate that astrocytes in the rat retina are
      coupled to each other and to Muller cells. The astrocyte-to-Muller cell coupling
      is asymmetric, allowing transfer of the tracer in the forward direction only. In
      addition, astrocyte-to-Muller cell coupling is more sensitive to the uncoupling
      agents tested than is astrocyte-to-astrocyte coupling.

PMID- 9145303
TI  - AMPA/kainate receptor activation blocks K+ currents via internal Na+ increase in
      mouse cultured stellate astrocytes.
AB  - Cultured mouse cortical astrocytes of the stellate type were studied by using the
      patch-clamp technique in whole-cell configuration. The astrocytes express at
      least two types of outwardly rectifying K+ channels which mediate a transient and
      a sustained current. Activation of AMPA receptors by kainate leads to a
      substantial blockade of both types of K+ currents. The blockade is absent when
      Na+ is withdrawn from the external medium, suggesting that it is caused by
      constant Na+ influx through AMPA receptors. The presence of high Na+ solutions in
      the pipette induces a blockade of both K+ currents which is very similar to the
      blockade induced by kainate, supporting thus the view that the mechanism of the
      blockade of K+ channels by kainate involves Na+ increases in the submembrane
      area. The blockade occurs between 20 and 40 mM [Na+]i, which is within the
      physiological range of [Na+]i in astrocytes. The data may suggest that the
      blockade of K+ channels by high [Na+]i conditions could provide a mechanism to
      prevent K+ leakage from the astrocytes into the extracellular space during
      periods of intense neuronal activity.

PMID- 9145302
TI  - Glucocorticoid- and mineralocorticoid receptors in microglial cells: the two
      receptors mediate differential effects of corticosteroids.
AB  - Effects of steroid hormones on the regulation of function and morphology of
      microglial cells were investigated using the cultured cells isolated from
      forebrain of newborn rats. Cortisol, corticosterone, and aldosterone at 100 nM
      caused a strong shrinkage of microglial cells cultured in a serum-supplemented
      medium. However, cholesterol, pregnenolone, testosterone, estradiol, and
      dehydroepiandrosterone did not exhibit any significant effects. The
      corticosteroids also inhibited the GM-CSF-mediated ramification of microglia in a
      serum-free medium. An anti-glucocorticoid agent RU38486 abolished the effects of
      corticosteroids on the microglial morphology, suggesting the presence of
      functional glucocorticoid receptor (GR) in microglial cells. The presence of GR
      was confirmed by immunoblotting with an antibody to the receptor. Cytokines GM
      CSF and interleukin-3 altered the level of GR expression. Binding experiments
      with [3H]-corticosterone demonstrated the presence of not only GR but also
      mineralocorticoid receptor (MR): the dissociation constants (Kd) and the number
      of binding sites (Bmax) were 0.8 nM and 15 fmol/mg protein for MR and 5.0 nM and
      73 fmol/mg protein for GR, respectively. The pure glucocorticoid RU28362 and
      dexamethasone at 20 nM (but not aldosterone and corticosterone at the same
      concentration) inhibited proliferation of microglial cells, as revealed by PCNA
      immunocytochemistry. RU28362 inhibited the activities of inducible nitric oxide
      synthase and acid phosphatase at concentrations higher than 1 nM. Aldosterone and
      corticosterone exhibited the similar inhibitory effect at 100 nM, and this
      inhibition was completely overcome by RU38486. On the other hand, corticosterone
      and aldosterone at concentrations lower than 1 nM enhanced the activities of both
      enzymes. The antimineralocorticoid agent spironolactone eliminated the
      stimulatory effects of corticosterone on the enzyme activities. In accordance
      with these biochemical results, electron microscopic observations revealed that
      glucocorticoids enhanced the formation of lysosomal vacuolation in microglial
      cells and aldosterone increased the number and size of lysosomes. In conclusion,
      it is suggested that GR and MR mediated the opposite effects of corticosterone on
      the functions of microglial cells; the hormone acted as an inhibitor through GR
      and as an stimulator through MR.

PMID- 9145304
TI  - Characterization of the hypo-osmolarity-induced Ca2+ response in cultured rat
      astrocytes.
AB  - The influence of astrocyte swelling on the cytosolic free calcium concentration
      [Ca2+]i was studied at the single cell level. Sudden exposure of normo
      osmotically (305 mosmol/l) cultured astrocytes to hypo-osmotic medium induced a
      biphasic increase in cytosolic calcium with an initial peak followed by a
      sustained plateau. The response was osmolarity dependent and was maximal at 205
      mosmol/l with respect to [Ca2+]i and the percentage of responding cells. Other
      modes of astrocyte swelling [gradual adjustment of hypo-osmolarity, normo-osmotic
      exposure of hyper-osmotic (405 mosmol/l) maintained cells] produced a much weaker
      [Ca2+]i response. Change from 405 to 205 mosmol/l, however, resulted in the
      entire peak and an increased plateau. Experiments with Ca(2+)-free medium and
      after pretreatment with BAPTA-AM, thapsigargin, phorbol myristate acetate, or
      nimodipine revealed that the peak mainly resulted from depletion of intracellular
      Ca2+ stores, whereas the plateau was probably due to capacitative Ca2+ entry and
      Ca2+ influx independent of store depletion including a nimodipin-sensitive
      component. Prior depletion of ryanodine-, bradykinin- or ATP-sensitive stores
      revealed that the initial hypo-osmolarity-induced Ca(2+)-release was from a Ca2+
      pool also affected by ATP and bradykinin, but not by ryanodine. The recent
      finding, that the hypo-osmolarity-induced [Ca2+]i response was completely
      maintained if phospholipase C-mediated phosphatidylinositol hydrolysis was
      blocked, suggests that hypo-osmolarity may exert an inositol (1,4,5) triphosphate
      independent access to these stores.

PMID- 9145305
TI  - Tumor necrosis factor and nitric oxide production by retinal Muller glial cells
      from rats exhibiting inherited retinal dystrophy.
AB  - The primary cause of the inherited retinal dystrophy observed in Royal College of
      Surgeons (RCS) rats is located in the retinal pigmented epithelium, which is
      unable to phagocytize photoreceptor outer segments. We have demonstrated here
      that retinal Muller glial (RMG) cells obtained from RCS dystrophic rats and
      stimulated in vitro with lipopolysaccharide (LPS) and interferon-gamma (IFN
      gamma) accumulated higher levels of tumor necrosis factor (TNF) and inducible
      nitric oxide synthase (NOS II) mRNA and released in culture supernatants
      significantly higher amounts of TNF and nitrite compared to cells derived from
      nondystrophic controls. The TNF and NOS II mRNA expression and TNF and nitrite
      synthesis induced in RMG cells from both strains by LPS + IFN-gamma was
      significantly prevented by including transforming growth factor-beta (TGF-beta)
      in the culture medium. Coincubation of the stimulants with an inhibitor of NOS
      II, NG-monomethyl-L-arginine (L-NMMA), while inhibiting nitrite synthesis,
      induced an increase of TNF production in supernatants from RMG cells without
      increasing TNF mRNA levels. The retinal dystrophy observed in RCS dystrophic rats
      could result from an abnormal susceptibility of RMG cells form RCS dystrophic
      rats to produce TNF and NO in response to stimulants. Administration of the
      immunomodulatory cytokine TGF-beta or inhibitors of NOS II would provide
      additional research avenues for photoreceptor rescue.

PMID- 9145306
TI  - Differential expression of voltage-gated Ca2+ conductances in human neuroblastoma
      NB69 cells cultured in defined serum-free and astrocyte-conditioned media.
AB  - Voltage-gated Ca2+ conductances were investigated with the whole-cell patch-clamp
      technique-either using Ca2+ or Ba2+ as charge carriers-in NB69 human
      neuroblastoma cells plated in "defined" serum-free (DM) and in "astroglial
      conditioned" media (CM). Cells expressed the microtubule associated protein 1A
      when plated in both media, indicating neuronlike differentiation. Cells of
      similar sizes and shapes were selected for recordings. Different sets of voltage
      gated Ca2+ current types were usually expressed in DM- and CM-plated cells. DM
      plated cells exhibited a high-voltage-activated current (HVAC) in isolation,
      whereas 43% of the CM-plated cells also displayed the low-voltage-activated
      current (LVAC). The membrane surface density of the HVAC was about twofold higher
      in CM than in DM-plated cells and increased with plating time from 10 and 16pA/pF
      (days 1-4) to 24 and 37 pA/pF (days 5-10) in DM- and CM-plated cells,
      respectively. However, the amplitude of the LVAC did not change significantly
      with culture age. In conclusion, NB69 cells expressed HVAC in isolation when
      plated in DM, whereas both HVAC and LVAC were present in many CM-plated cells,
      suggesting that the CM contained diffusible factors secreted by astroglial cells
      which: (1) could induce the appearance of the LVAC and (2) increased HVAC current
      expression.

PMID- 9145307
TI  - Glutamate metabolism is down-regulated in astrocytes during experimental allergic
      encephalomyelitis.
AB  - Experimental allergic encephalomyelitis (EAE) was induced in SJL/J mice by
      adoptive transfer of MBP-reactive T cells in order to investigate the role of
      astrocytes in pathology. GFAP protein and mRNA expression (analyzed using
      semiquantitative Western blot and RT-PCR techniques) were upregulated in the
      spinal cord of mice, which had developed a complete paralysis of hind- and fore
      limbs and tail (grade 4 EAE), thus establishing that reactive gliosis occurred
      under these experimental conditions. Within the same samples and using similar
      techniques, we found that glutamine synthetase (GS) and glutamate dehydrogenase
      (GDH) expression were dramatically reduced. These two astrocytic enzymes are
      responsible for degradation of glutamate, the most abundant excitatory
      neurotransmitter in the brain. Since elevated levels of glutamate may be
      neurotoxic, we propose that the decreased capacity of astrocytes to metabolize
      glutamate may contribute to EAE pathology.

PMID- 9145308
TI  - [Community health care and medicine--on a view point of the Japan Medical
      Association].

PMID- 9145309
TI  - [Recent trend toward development of community medicine].
AB  - The author evaluated the present status of community medical activities in
      Hokkaido from standpoint of various actual data obtained by recent investigation.
      As many districts are in the face of shortage of doctors, it is concluded to
      promote the following subjects, 1) strengthening of district center hospitals, 2)
      education and maintenance of community medical doctors, 3) synthetic system of
      health, medicare and welfare, and 4) introduction of multimedia system. Our
      foundation has started several new works, such as doctor center model system,
      training system of primary care doctor, and network activities of community
      doctors. It is mandatory to form wide consensus among the person concerned, such
      as client, doctor, medical association, university, and municipality.

PMID- 9145310
TI  - [Morphological study of muscle fibers stained red by modified Gomori trichrome
      staining with special reference to smooth red fibers].
AB  - The modified Gomori trichrome stain of muscles can demonstrate ragged red fibers
      which are irregular in outline and display a thick and irregular red
      subsarcolemmal layer and intermyofibrillar red deposits. Typical ragged red
      fibers are often encountered in mitochondrial myopathy. On the other hand, we
      have noticed fibers outlined by a thin red subsarcolemmal layer. These fibers are
      smooth in outline. The sarcoplasm shows normal intermyofibrillar network. We
      defined these fibers as "smooth red fibers". To investigate the pathological
      significance of the smooth red fibers, we studied morphological differences
      between the smooth red fibers and ragged red fibers by light and electron
      microscopy and evaluated the occurrence and characteristics of the both abnormal
      muscle fibers in several neuromuscular diseases. Muscle specimens from 738
      patients who were seen or consulted at the Department of Neurology, Hokkaido
      University, from January 1980 to October 1994 were examined. The smooth red
      fibers were classified into two types, type I and type II. Type I smooth red
      fibers were hypertrophied and showed a thin smooth red margin. Electron
      microscopy of the type I smooth red fibers showed no mitochondrial abnormality,
      being different from ragged red fibers which have abnormal mitochondria. Type I
      smooth red fibers were observed in chronic denervation process; they were
      specially frequent in Kugelberg-Welander syndrome. Hypertrophy of type I smooth
      red fibers were considered to be a compensative reaction in chronic denervation.
      Type II smooth red fibers were observed with or without ragged red fibers in
      mitochondrial myopathy. Type II smooth red fibers showed a thin smooth red
      margin, spreading red deposits from the margin into sarcoplasm. The fibers showed
      mitochondrial abnormality in electron microscopy. It could be posturated that
      type II smooth red fibers were transformed into ragged red fibers. The findings
      suggest 1) type I and type II smooth red fibers are different in origin, 2) type
      II smooth red fibers change to ragged red fibers, 3) type I and type II smooth
      red fibers are important markers of chronic denervation and mitochondrial
      myopathy, respectively. These two types of smooth red fibers are worthy of
      attention in muscle pathological observations.

PMID- 9145311
TI  - [Influence of methylprednisolone and transforming growth factor-beta on wound
      healing].
AB  - This study was aimed at evaluating the influence of transforming growth factor
      beta (TGF-beta) on methylprednisolone induced inhibition of wound healing.
      C57BL/6 mice underwent a standardized dorsal incision. At regular intervals after
      wounding the mice were sacrificed and their pelts were excised. The fresh
      breaking strength (FBS) of the pelts was then measured with a constant-speed
      tension meter. 1) In the first experiment, designed to determine if
      methylprednisolone did in fact have any inhibiting effect on wound healing, mice
      received methylprednisolone and a control group received saline. Both
      methylprednisolone and saline were administered for a four day period. In this
      experiment the FBS of methylprednisolone treated mice was weaker than that of the
      control group on the 14th and the 21st day. 2) In the second experiment, designed
      to determine when the administration of methylprednisolone most noticeably
      inhibited wound healing, mice were divided into three groups which received
      methylprednisolone in the following manner: for three days prior to wounding, on
      the day of wounding, and for three days immediately following wounding. The
      fourth group received no methylprednisolone at all. The FBS of mice treated with
      methylprednisolone for three days prior to wounding was weaker than that of the
      control group on the 14th day after wounding, but showed no significant
      difference on the 21st day after wounding. The FBS of mice treated on the
      operative day was weaker on both the 14th and the 21st day after wounding. The
      FBS of mice treated three days after wounding showed no significant difference on
      the 14th day after wounding, but was weaker than the control group on the 21st
      day after wounding. 3) In the third experiment, designed to determine at what
      time the administration of TGF-beta most accelerated wound healing, mice were
      divided into three groups which received TGF-beta at different intervals. The
      first group received TGF-beta on the day of wounding, the second group received
      TGF-beta on the third day after wounding, and the third group received TGF-beta
      on the 7th day after wounding. A control group received no treatment. In this
      experiment the FBS of mice treated with TGF-beta on the third day after wounding
      was stronger than that of the control group when measured on the 7th and 11th day
      after wounding, but there was no significant difference on the 14th day. The FBS
      of mice treated on the day of wounding and mice treated on the 7th day after
      wounding was not significantly different from that of the control group. 4) In
      the fourth experiment, designed to determine if TGF-beta can prevent
      methylprednisolone-induced inhibition of wound healing, mice were divided into
      three groups. The first group received methylprednisolone for four days prior to
      wounding. On the third day after wounding they were given saline. The second
      group also received methylprednisolone for four days prior to wounding, but was
      treated with TGF-beta on the third day after wounding. The third group received
      no methylprednisolone, and was given saline three days after wounding. In this
      experiment the FBS of mice which received only methylprednisolone and saline was
      weaker than that of the control group on both the 14th and the 21st day after
      wounding. However, there was no significant difference between the FBS of
      methylprednisolone treated mice which received TGF-beta and the control group on
      both the 14th and the 21st day after wounding. From these results the following
      conclusions were drawn: 1) Methylprednisolone does inhibit wound healing. 2) The
      influence of methylprednisolone on wound healing is stronger if it is received on
      operative day. 3) TGF-beta can accelerate wound healing. 4) TGF-beta can prevent
      methylprednisolone induced inhibition of wound healing.

PMID- 9145312
TI  - [Selective induction of effector functions in a T cell clone following antigen
      presentation in the presence of thymic epithelial cells].
AB  - Selective induction of effector functions in a T cell clone, DB14, specific for
      pigeon cytochrome c 43-58 (p43-58) and restricted to I Ab was analyzed using
      professional antigen presenting cells (APC), B hybridoma (Th2.58), and various
      non professional APC, L cells transfected with I Ab (I-Ab L cells), a medullary
      thymic epithelial cell line (m-TEC) and a cortical thymic epithelial cell line (c
      TEC). The m-TEC and c-TEC (m, c-TEC) expressed I-Ab after culturing with
      interferon-gamma (IFN-gamma). When stimulated with p43-58 in the presence of I-Ab
      L cells as well as Th2.58 cells, the DB14 cells showed marked proliferation and
      exhibited significant cytotoxicity against these APC after 18 hr of culture. By
      contrast, in the presence of m, c-TEC the DB14 cells showed neither proliferation
      nor cytotoxicity against these TEC but exhibited considerable detachment activity
      against them. Furthermore DB14 cells became expressed activation markers (CD69
      and CD44) after antigen (p43-58) stimulation with m-TEC or c-TEC. Addition of rIL
      2 to the culture of DB14 cells, p43-58 and m, c-TEC restored the proliferative
      responses. However, it was shown that anergy was not involved in the lack of
      proliferative response of DB14 cells after antigen stimulation with m, c-TEC. The
      present findings indicate that differences in APC function are present among non
      professional APC and suggest that the selective induction of T cell functions can
      be achieved using appropriate non-professional APC. The characteristic activation
      of T cells by TEC may be related to their functional roles in situ.

PMID- 9145313
TI  - [Detectability and diagnostic criteria of p53 gene mutations in human oral
      squamous cell carcinoma using yeast functional assay].
AB  - In yeast functional assay (YF assay), a newly developed screening system for p53
      mutation, wild-type p53 gives white yeast colonies and transcriptionally inactive
      mutant p53 gives red colonies. In the present study, the author applied YF assay
      to the detection of p53 mutations in human oral squamous cell carcinoma (SCC).
      Total RNA was extracted from samples and YF assay was performed. Four SCC cell
      lines (SAS, HSC-2, HSC-3 and Ca9-22) known to have p53 mutations all gave 100%
      red colonies, whereas nine oral non-tumor tissues gave 2.9-10% (average 5.2 +/-
      2.7%) red colonies. Furthermore, a rat hepatoma cell line, WHp53, which had been
      transfected with human wild-type p53 expression vector, presented 7.8% red
      colonies. Thus the functional assays of tissues or cells containing only wild
      type p53 give 3-10% red colonies as a background. To assess the detectability of
      p53 mutations, YF assay was performed on mixtures of wild-type and mutant p53 PCR
      products at serial ratios. The result showed that the mutation was detectable if
      6% population of transcriptionally inactive mutant p53 mRNA were present in the
      total p53 mRNA. Twenty-two clinical samples of human oral SCC were then tested by
      YF assay. Fourteen out of 22 cases gave more than 20% red colonies. In these 14
      cases, clonal p53 mutations with deletion, nonsense mutation or missense mutation
      were identified. In a case which gave 17% red colonies, identical p53 mutation
      was found in 2 out of 6 independent red colonies. However, no identical mutations
      were found in the cases giving 13, 9 and 8% red colonies. Based on these results,
      the author proposes that 20% of red colonies is the minimal value for the
      diagnosis of p53 mutation in YF assay under PCR conditions using Pfu polymerase
      and hot start method.

PMID- 9145314
TI  - [Arterialization of the capillary network in the left ventricular subendocardium
      in young rats subjected to exercise training].
AB  - The increase in cardiac activity requires an increase in oxygen supply to the
      ventricular tissues. Two adaptational changes in the capillary network seem to
      increase the oxygen supply; one is the increase in capillary density and the
      other may be the increase in arteriolar capillaries. To test this hypothesis,
      double staining method, which was validated by microsphere injection, was used
      for differentiation of arteriolar and venular capillaries in exercise-trained
      rats in the present study. Male Wistar rats after weaning (3 weeks old) were
      subjected to treadmill running 1 hour/day in the evening, 6 days/week. The
      running speed was increased from 10 m/min without gradient to 25 m/min with a 7%
      gradient for 6 weeks. The total capillary density and capillary to myocyte ratio
      increased significantly. Capillary domain area decreased, suggesting neoformation
      of capillaries. In support of the capillary increase two stimulators for
      angiogenesis, vascular endothelial growth factor and basic fibroblast growth
      factor were immunohistochemically stained in the ventricular tissues from
      exercise-trained rats. Capillary of arteriolar type increased with a decrease in
      the venular capillary. The arteriolar portion of capillaries became significantly
      longer and the venular portion shorter than in resting control rats. Branching of
      capillaries increased both in the arteriolar and venular portions. These results
      suggest that the arterialization of capillary network proceeded with the increase
      in the capillary density to facilitate the oxygen transport to cardiac tissues.

PMID- 9145315
TI  - Characterization of the ETSA-21 antigen, a glycosylphosphatidyl-inositol anchor
      glycoprotein identified in breast cancer cells using monoclonal antibody B21.
AB  - Mab B21 is a monoclonal antibody (Mab) that recognizes an epithelial tumor
      surface antigen (ETSA-B21) from diverse human tumor cell lines including breast,
      ovary, uterus, and their cognate carcinoma tissues. A lower reactivity has been
      observed in normal breast tissue and benign hyperplesia. In this study, the
      characteristics of the ETSA-B21 antigen have been examined in greater detail in
      the MCF-7, SK-BR-3, and MDA-MB-453 breast cancer cell lines. Treatment with
      phosphatidylinositol-phospholipase C, but no neuraminidase were found to
      partially remove the ETSA-B21 signal from the cell surface as revealed by
      immunofluorescence microscopy. Inhibition of the N-glycosylation pathway by
      tunicamycin resulted in a decreased ETSA-B21 signal on the cell membrane. In
      addition, the antigen-antibody complex was internalized in breast cancer cells as
      demonstrated by an acidic was internalization assay evaluated using
      immunofluorescence. In conclusion, this study suggests that ETSA-B21 is a GPI
      anchor N-glycosylated protein promoting specific antibody internalization in
      breast cancer cells.

PMID- 9145316
TI  - Clinical and immunologic effects of monoclonal antibody CC49 and interleukin-2 in
      patients with metastatic colorectal cancer.
AB  - We examined the possibility that prior exposure to the murine monoclonal antibody
      (mAb), CC49, which recognizes the pancarcinoma antigen, TAG-72, would modify the
      clinical activity of interleukin-2 (IL-2) in patients with metastatic colorectal
      cancer. Fourteen patients received 2 mg of unconjugated CC49 on Day 1; on Day 22,
      they began human recombinant IL-2 at 1 mg/m2/day for 4 days by continuous IV
      infusion. Four-day cycles of IL-2 were repeated weekly for 8 weeks unless there
      was evidence of unacceptable toxicity or progressive disease. Therapy was well
      tolerated. Proliferative responses of peripheral blood mononuclear cells (PBMC)
      to CC49, its Fab fragment, isotype matched murine immunoglobulin, and CC49
      complexed with TAG-72+ mucin increased after CC49 administration (Day 21). These
      proliferative responses decreased after IL-2 administration. PBMC proliferative
      responses to AI49, an anti-CC49 idiotype antibody (Ab2), and TAG-72+ mucin was
      not induced. No complete or partial clinical responses were observed; one patient
      manifested a transient mixed response. A single infusion of CC49 does have
      biologic activity; it is, however, unlikely to substantially modify tumor
      response rates effected by IL-2 in patients with metastatic colorectal cancer.

PMID- 9145317
TI  - Epitope localization of monoclonal antibodies used in human troponin I
      immunoenzymometric assay.
AB  - Serum troponin I isoforms have proven to be potent markers of striated muscle
      injury. They reach the blood-stream soon after their liberation from the damaged
      muscular cell and can be detected by the use of selected antibodies. Among
      monoclonal antibodies (MAbs) originally produced against cardiac troponin I
      (cTnI), two MAbs able to cross react with the skeletal isoform of troponin I
      (sTnI) were selected and used to develop a one-step immunoenzymometric assay
      which allows the quantification of both cardiac and skeletal isoforms (scTnI
      IEMA). The present report describes the main characteristics of this assay. By
      using multiple peptide synthesis methods, the localization of the epitopes
      recognized by the two MAbs on sTnI were determined. The capture and tracer MAbs
      of the scTnI IEMA were shown to recognize epitopes located within positions 121
      127 and 160-167 in the sTnI sequence, respectively. The results of this epitopic
      analysis are discussed in light of the cross reaction of these two MAbs with
      cTnI.

PMID- 9145318
TI  - Monoclonal antibodies against cathepsin L and procathepsin L of different
      species.
AB  - Mouse monoclonal antibodies directed against cathepsin L and procathepsin L have
      been generated. Mice were immunized with human procathepsin L purified from the
      cell culture medium of human nonsmall cell lung cancer cell line EPLC 32 M1. More
      than 400 hybridoma clones were screened by ELISA or Western blot and 50 were
      found to secrete antibodies which reacted with cathepsin L or its precursor.
      Twenty-six clones were selected for further characterization of the antibodies
      according to their reactivity in ELISA, Western blot, and immunocytochemistry
      against the mature enzyme or its latent precursor of man, rat, or mouse. Only
      those antibodies are described here, which do not cross-react with the closely
      related cathepsins B and S or their latent proenzymes.

PMID- 9145319
TI  - Production and characterization of a novel monoclonal antibody against
      phosphorylated T cell receptor zeta chain.
AB  - One of the earliest events following T cell receptor (TCR) triggering is the
      activation of the protein kinase Lck and induction of tyrosine phosphorylation of
      zeta, the major signal transduction subunit of the T cell receptor complex. Here
      we report the generation and characterization of a monoclonal antibody specific
      for human phosphozeta. The antibody was produced by immunizing mice with a
      truncated recombinant form of human zeta together with the Lck enzyme. The
      C415.9A antibody recognizes recombinant as well as cellular phosphozeta but is
      unreactive with unphosphorylated zeta or other tyrosine phosphorylated proteins.
      Using this antibody, we have demonstrated aberrant TCR-zeta tyrosine
      phosphorylation in Jurkat T cell transduction mutants. Therefore, this antibody
      can be used to elucidate T cell signal transduction mechanisms by analyzing and
      monitoring tyrosine phosphorylation of zeta in vitro and in vivo directly.
      Furthermore, this antibody could find application in the analysis of abnormal T
      cell signaling in autoimmune disease, cancer, and immunodeficiency disorders.

PMID- 9145321
TI  - Characterization and application of a strain-specific monoclonal antibody against
      the rhizosphere bacterium Azospirillum brasilense Wa5.
AB  - A hybridoma cell line producing a rat monoclonal antibody (MAb Bo-33) directed
      against lipopolysaccharide of Azospirillum brasilense Wa5 has been established
      and characterized. Whole bacteria were used as immunogens. The number of antigens
      per cell was about 1500. The number of antigens per cell of reisolates from the
      rhizosphere of what was similar to the number of antigens of bacteria cultivated
      in rich medium. The sensitivity of detection using MAb Bo-33 was about 100
      bacteria/ml. Therefore, the MAb was suitable for in situ immunofluorescence
      detection and a sensitive direct quantification of Azospirillum brasilense Wa5 in
      rhizosphere extracts.

PMID- 9145320
TI  - Characterization of monoclonal antibodies specific to human tartrate-resistant
      acid phosphatase.
AB  - A major product of osteoclasts, tartrate-resistant acid phosphatase (TRAP) is an
      essential but insufficient enzyme for bone resorption. TRAP is an excellent cell
      marker for osteoclasts and macrophages and is being investigated as a serum
      marker for osteoclast activity in diseases of bone destruction. For decades, TRAP
      has also been used as a marker for hairy cell leukemia. Immunoassays for TRAP are
      sought to increase the sensitivity and specificity of the TRAP test for bone and
      hairy cells. Our laboratory recently developed a monoclonal antibody to TRAP
      (9C5) useful for immunohistochemical identification of TRAP-positive cells in
      paraffin sections. Herein, we characterize 9C5 in greater detail and report
      production of another anti-TRAP monoclonal antibody antibody (14G6) reactive with
      native, active enzyme antigen. Enzyme immunoassay, immunoprecipitation, western
      blot, and immunohistochemical analyses revealed the contrasting properties of 9C5
      and 14G6. Antibody 9C5 reacts with a heat-denatured epitope and is suitable for
      denaturing western blot analysis and for immunohistochemistry. Antibody 14G6
      reacts with a conformational determinant destroyed by heat and is suitable for
      immunoprecipitation of active TRAP, although 20% to 30% of activity is inhibited
      in the immune complexes. Having characterized several properties of these anti
      TRAP antibodies, 9C5 and 14G6 may be useful for development of TRAP-specific
      immunoassays in bone pathology and hematology. They will certainly be of use for
      the study of biosynthesis, regulation, expression, and function of TRAP.

PMID- 9145322
TI  - Monoclonal antibodies to thymidine glycol generated by different immunization
      techniques.
AB  - Monoclonal antibodies specific for thymidine glycol in oxidized DNA were
      generated by immunization with thymidine glycol monophosphate (TMP-OH) or
      thymidine glycol (T-OH), respectively, conjugated to keyhole limpet hemocyanin
      (KLH) or thyreoglobulin (TG). Forty-five clones (TMP-OH) and 70 clones (T-OH)
      were examined upon antibody production in ELISA. Four clones secreting IgG1,
      kappa, were characterized further. In several studies the antibodies derived from
      the immunization with TMP-OH were inhibited by various inhibitors. In descending
      order of effectiveness, they were thymidine glycol monophosphate (TMP-OH),
      thymidine glycol (T-OH), thymidine monophosphate (TMP), and thymidine (Thn).
      After immunization with T-OH, antibodies were inhibited in following order: T-OH
      > TMP-OH > TMP > Thn. Inhibition by the bases thymine, adenine, cytosine, and
      guanine were negligible. In ISB (Immuno Slot Blot) performed with OsO4-treated
      DNA (Poly-[dA-dT]) and amount of 70 fmol thymidine glycol was detectable. DNA had
      to be irradiated at a level of at least 20 Gy to detect any damage in ELISA but
      at a lower level of irradiation (10 Gy) in ISB by one of these antibodies, TPS-1.
      The antibodies obtained after immunization with hapten-protein are therefore
      capable of the detection of low frequency lesions in DNA generated by free
      radicals after radiation or oxidative stress.

PMID- 9145323
TI  - Detection of two isotypically different antibodies produced by a murine
      hybridoma.
AB  - A hybridoma, F31P46B, secreting monoclonal antibodies (mAbs) comprised of mu and
      gamma heavy chains in association with a single kappa light chain, has been
      characterized. This hybridoma was prepared by fusing splenocytes, derived from a
      BALB/c mouse immunized with Vibrio vulnificus and SP2/O-Ag-14 mouse myeloma
      cells. The specificity of this hybridoma was determined by ELISA screening on a
      large number of bacterial strains. Hybridoma cells of F31P46B were cloned by
      limiting dilution to an average cell density of 0.1 cells/well and repeated 3
      times to ensure monoclonality. Isotyping of 7 subclones was then performed by
      Ouchterlony gel double diffusion, as well as a Bio-Rad isotyping kit, and both
      methods showed that both IgM and IgG2b were secreted. PAGE and immunoblotting
      showed the presence of mu, gamma, and kappa chains with respective molecular
      weights of 80, 50, and 25kDa. A series of fractions, collected from F31P46B
      ascites during Superose 12 gel chromatography, were tested by the two isotyping
      methods and each confirmed the presence of two immunoglobulin products. These
      data indicated that the hybridoma secreted two separate immunoglobulins,
      IgM/kappa and IgG2b/kappa.

PMID- 9145324
TI  - The major component of Na-CBZ-L-lysine thiobenzyl ester (BLT)-specific proteases
      in cytoplasmic granules of murine intraepithelial lymphocytes is granzyme A.
AB  - Na-CBZ-L-lysine thiobenzyl ester (BLT)-specific proteases in cytoplasmic granules
      of intraepithelial lymphocytes in the murine intestine (iIEL) were characterized.
      BLT-specific proteases were isolated with the Sephacryl S-200 column
      chromatography, and the sample isolated contained a protein with a molecular
      weight of 58 kDa. The 58 kDa protein consisted of the homodimer of the 30 kDa
      subunits. The 58 kDa protease was detected by [3H] diisopropylfluorophosphate
      (DFP)-labeling, and also detectable by the immunoblotting using an antibody
      against the partial synthetic peptide of granzyme A. The cytoplasmic granules of
      iIEL were stained positively by an immunofluorescence with anti-granzyme A
      antibody. Therefore, it was suggested that the major BLT-specific proteases
      present in cytoplasmic granules of iIEL might be granzyme A.

PMID- 9145325
TI  - Co-development of naive CD4+ cells towards T helper type 1 or T helper type 2
      cells induced by a combination of IL-12 and IL-4.
AB  - Cytokines were found to play a key role in Th cell differentiation. Among them IL
      12 was shown to be a potent differentiation factor for Th1 cells, whereas IL-4 is
      the only known cytokine that promotes the development of Th2 cells. Upon addition
      of comparable amounts of IL-4 and IL-12 to a primary culture of naive CD4+ T
      cells activated by immobilized anti-CD3 mAb, it was found that the Th1-inducing
      capacity of IL-12 is dominated by the Th2-promoting effect of IL-4. However, high
      amounts of IL-12 (10,000 U/ml) in combination with low amounts of IL-4 (100 U/ml)
      led to the development of a Th cell population that, upon rechallenge, showed a
      substantial secondary IFN-gamma (Th1 cytokine) production concomitantly with the
      production of high amounts of IL-4 (Th2 cytokine). This can be due to the
      coexistence of Th1 and Th2 cells or to the development of Th0 cells producing a
      mixed pattern of cytokines. Immunofluorescence double staining of intracellular
      IL-4 and IFN-gamma in combination with flow cytometry (FACS) revealed that most
      of the emerging Th cells produced either IL-4 or IFN-gamma. Only a few double
      producers could be detected. This finding indicates that individual naive CD4+ T
      cells can differentiate under the same conditions towards Th1 or Th2 cells and
      implicates that the development of Th1 and Th2 cells is not necessarily mutually
      exclusive.

PMID- 9145326
TI  - Characterization of T cells transmigrating through human endothelial cells in
      patients with HTLV-I-associated myelopathy.
AB  - We investigated the surface markers as well as the expression of beta 2-integrin
      (LFA-1 beta/CD 18), in T cells migrating through human umbilical vein endothelial
      cells (EC) in patients with HTLV-I-associated myelopathy (HAM). No significant
      differences were found in the percentages of both HLA-DR+ T cells and total CD4+
      cells and in the expression of beta 2-integrin between the EC-transmigrated and
      the EC adherent T cells. However, the percentages of HLA-DR+CD4+ cells in the
      transmigrated cells were significantly higher than those in the adherent cells.
      These results suggest that activated or HLA-DR+CD4+ T cells play an important
      role as the first trigger in the immunopathogenesis of HAM.

PMID- 9145327
TI  - Homologous complement activation on drug-induced apoptotic cells from a human
      lung adenocarcinoma cell line.
AB  - Activation of the alternative pathway of homologous complement (C) was observed
      in a human lung adenocarcinoma cell line, CADO 43, after the cells had become
      apoptotic following treatment in vitro with vincristine and predonisolone.
      Deposition of C3b and C3bi on the serum-treated apoptotic cells was revealed by
      flow cytometry with anti-C3b and -C3bi-specific antibodies and immunoblotting
      with anti-C3 antibody immunoprecipitates extracted from solubilized fractions of
      serum-treated apoptotic cells. Two molecular mechanisms were found to be
      responsible for this post-apoptotic C-activation. Firstly, all C regulators,
      decay accelerating factor (DAF), membrane cofactor protein (MCP) and C3b/C4b
      receptor (CR1), were diminished on the cell surface concomitantly with the
      apoptotic process. Secondly, unidentified molecules which potentially activate
      homologous C and accept C3b/C3bi fragments became expressed on the cell surface
      during the apoptotic process. These findings may explain the mechanism whereby
      tumor cells are efficiently eliminated through chemotherapy.

PMID- 9145328
TI  - Binding of human leukocytes to fibronectin is augmented by an anti-CD44 mAb (TL
      1) and blocked by another anti-CD44 mAb (Hermes-3) but not by anti-VLA-4/VLA-5
      mAbs.
AB  - Fibronectin (FN) forms meshworks in extracellular spaces, and it plays an
      important role in cellular trafficking. Lymphoid cells are activated by binding
      to FN of the VLA-4 and VLA-5 receptors. CD44 also acts as a receptor of FN, but
      the mechanism and physiologic regulation of their binding are poorly understood.
      We have developed an anti-CD44 monoclonal antibody (mAb) (TL-1) in which lymphoid
      cells are activated and form homotypic cell aggregation. In this study, we found
      that the adhesion of CEM, HSB2, and LAD lymphoid cells to FN was augmented by TL
      1 treatment and was apparently blocked by another anti-CD44 mAb (Hermes-3), but
      TL-1 Fab' fragments treatment did not induce FN-binding. A similar phenomenon is
      reported in the binding of the CD44 molecule to HA. This augmentation was not
      inhibited by the CS1 and RGD peptides of FN or by anti-VLA-4 and -VLA-5 mAbs; it
      was energy-dependent and associated with cytoplasmic actin filaments. Tl-1
      treatment did not alter the cell surface expression of CD44 molecules. These
      findings above suggested that activated and/or altered cell surface distribution
      of CD44 molecules via a conformational change augmented the avidity of its
      binding to FN, which may be similar to lymphocyte-hyaluronate and lymphocyte
      endothelial cell binding. As the Hermes-3 binding site is also involved in the
      interaction between lymphocytes and endothelial cells, activation of lymphocytes
      via CD44 molecules may facilitate the binding of lymphocytes to endothelial
      cells, extravasation, and migration to inflammatory sites rich in FN.

PMID- 9145330
TI  - Differential effects of cell adherence on LPS-stimulated cytokine production by
      human monocytes and macrophages.
AB  - It is well known that adherence of monocytes (MO) to extracellular matrix
      substrates or tissue culture plastic activates these cells and induces the
      expression of a multitude of genes. Especially, it was described, that MO are
      primed by cell adhesion to produce higher amounts of some cytokines, e.g.
      interleukin (IL)-8 and tumor necrosis factor alpha (TNF-alpha). In order to
      investigate adherence-induced effects upon cytokine production, we seeded MO into
      tissue cultures and stimulated cells by lipopolysaccharide (LPS) simultaneously
      or at later time points. An increasing time-lag between cell adhesion and LPS
      stimulation led to differential effects upon cytokine production: whereas TNF was
      upregulated (in accordance with reports by others), granulocyte colony
      stimulating factor (G-CSF) was considerably down-regulated. In contrast, G-CSF
      production did not change, when cells were kept under non-adherent conditions in
      whole blood. In adherent cultures down-regulation of G-CSF could already be
      observed after two hours with a maximum after 24 h and was paralleled by a much
      lower abundance of G-CSF mRNA. Adhesion induced a significant suppression of G
      CSF comparable to MO, if mature macrophages derived from MO in vitro were
      examined. Furthermore, two other cytokines, granulocyte-macrophage (GM)-CSF and
      IL-6, were also down-regulated following adhesion. In conclusion, activation of
      mononuclear phagocytes by adhesion can lead to "priming" for the production of
      some cytokines and at the same time to "silencing" for the production of others.

PMID- 9145329
TI  - Anti-thymocyte globulin treatment of a patient for paroxysmal nocturnal
      haemoglobinuria-aplastic anaemia syndrome: complement activation and transient
      decrease of the PNH clone.
AB  - Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal stem cell
      disorder resulting in insufficient and defective haematopoesis associated
      frequently with aplastic anaemia (AA). A deficiency of the glycosyl
      phosphatidylinositol (GPI)-anchored complement activation regulatory proteins
      CD55 and CD59 is responsible for an increased sensitivity of erythrocytes to
      complement attack leading to chronic intravascular haemolysis with
      haemoglobinuria. In this study we investigated the effects of complement
      activation caused by anti-thymocyte globulin (ATG) treatment on the PNH clone in
      a patient affected with the PNH/AA-syndrome. Fluid phase complement components
      C3, C4, C6 and terminal complement complex (TCC) were assayed by ELISA. CD55,
      CD59 and cell-associated TCC were monitored by flow cytometry. ATG treatment
      resulted in profound systemic complement activation which led to a decrease in
      the levels of native C3 and C4 to 65% and 40%, respectively, of the original
      levels on day 5 and of C6 and TCC to 61% and 23%, respectively, on day 10. A
      return to pre-treatment levels was observed for C3 by day 15, for C6 by day 30
      and for C4 by day 90. Flow cytometry revealed that the deficiency in the GPI
      anchored protein was restricted to granulocytes, while lymphocytes remained
      unaffected. Cell-bound TCC increased by 1.67-fold and 2.37-fold on day 5 and day
      10, respectively, decreasing to 1.40-fold and 1.30-fold on day 15 and day 30,
      respectively. The percentage of PNH granulocytes as identified by the absence of
      the CD55- and CD59-antigens exhibited a temporary decrease from 72% on day 0 to
      65% on day 5 and 59% on day 10 and returned thereafter to the original percentage
      of 70% by day 15 and exceeding this level to 76% on day 30 and 79% on day 90. We
      report profound activation of the classical pathway of the complement cascade and
      the terminal complement complex by the globulin leading to a transient decrease
      of the PNH clone, presumably due to subsequent lysis of the PNH cells devoid of
      complement regulatory proteins.

PMID- 9145331
TI  - Recombinant Treponema pallidum antigens in syphilis serology.
AB  - Treponema pallidum, the etiological agent of syphilis, is characterized by a
      paucity of surface exposed outer membrane proteins and a high content of
      cytoplasma membrane associated lipoproteins. At all stages of infection intense
      antibody responses against lipoproteins are detectable. In order to provide
      antigens for syphilis diagnosis the highly immunogenic lipoproteins TpN17, TpN29
      35 (TpD), TpN44.5 (TmpA), TpN47, and TpN35 (TmpC) and the membrane protein TpN39
      (BMP) were cloned. Insertion of PCR amplified DNA into an E. coli expression
      vector resulted in high level expression of antigens. N-terminal hexahistidine
      sequence allowed efficient purification of fusion proteins by metal chelate
      affinity chromatography. The recombinant antigens were tested in enzyme-linked
      immunosorbent assays. TpN17, TpN47, and TpN44.5 antigens showed high antibody
      titers. Assays with the three antigens combined resulted in a further improvement
      of diagnostic sensitivity in comparison with single antigens. Antibodies were
      found in 17 of 18 patients in all stages of syphilis, whereas 42 normal human
      sera were nonreactive. No cross-reactivity was detected in 24 sera of patients
      with Lyme borreliosis.

PMID- 9145332
TI  - An unique CD4+CD8+ intestinal intraepithelial lymphocyte specific for DnaK
      (Escherichia coli HSP70) may be selected by intestinal microflora of rats.
AB  - We have previously shown an age-associated increase in unique CD4+CD8+ intestinal
      intraepithelial lymphocytes (i-IEL) in rats. To elucidate the potential causes of
      the increase in CD4+CD8+ i-IEL with age, we analyzed the specificity of the
      CD4+CD8+ i-IEL and influence of intestinal microflora on the increase in this
      subset in aged rats. The purified CD4+CD8+ i-IEL proliferated in response to DnaK
      [Escherichia coli (E. coli) HSP70] in the presence of mitomycin-c (MMC)-treated
      syngeneic spleen cells. The proportion of CD4+CD8+ T cells in whole i-IEL were
      significantly increased in aged rats fed commercial (CL-2) diet but not in those
      fed home-made (purified) diet under conventional condition. No CD4+CD8+ i-IEL
      were detected in aged rats under germfree condition, irrespective of diet
      feeding. A larger number of Enterobacteriaceae, especially E. coli, were detected
      in the intestinal contents and feces from aged rats with CD4+CD8+ i-IEL compared
      with those from aged rats fed without CD4+CD8+ i-IEL. The unique CD4+CD8+ i-IEL
      population specific for E. coli HSP may be associated with long term exposure to
      intestinal E. coli in aged rats.

PMID- 9145333
TI  - Lymphocyte response to silica among offspring of silicone breast implant
      recipients.
AB  - The current study evaluated immune response to silicon dioxide in children born
      to women with silicone breast implants. In part one of the study, the T
      lymphocytes of 21 of 24 such children were significantly stimulated by silicon
      dioxide (silica). Part two consisted of eleven children, four born
      preimplantation and seven born postimplantation. None of the preimplant offspring
      showed T cell responses to silica; five of the seven postimplant children were
      positive for T cell memory for silica. Part three was a blinded study based on
      statistically significant differences in T cell stimulation with silicon dioxide
      between postimplant children and controls. These findings indicate a common
      immune reaction, that of T cell memory, occurs in mothers and their children born
      after exposure to silicone mammary implants placed prior to pregnancy. Since not
      all such children were breast fed the result favors transplacental passage of
      immunogens such as silicone oligomers or through maternofetal cellular traffic.

PMID- 9145334
TI  - Cytokine gene expression in immune mice reinfected with Mycoplasma pneumoniae:
      the role of T cell subsets in aggravating the inflammatory response.
AB  - Cytokine gene expression was examined by qualitative and semiquantitative reverse
      transcriptase polymerase chain reaction (RT-PCR) in the lungs of Mycoplasma
      pneumoniae infected immune C57BL/6 mice depleted of either CD4+, CD8+ or both
      CD4+ and CD8+ T cells. Immediately after M. pneumoniae reinfection of control
      immune mice, mRNAs for TNF-alpha, IFN-gamma, IL-1 beta, IL-6, IL-2 and IL-2
      receptor were promptly detected in the lungs. In animals depleted of CD4+ T
      cells, mRNA expression for IL-2, IL-2 receptor and IFN-gamma were completely
      abrogated and mRNA expression for TNF-alpha, IL-1 beta and IL-6 were reduced by
      10- to 100-fold. In mice depleted of CD8+ T cells, mRNA expression for IL-2 and
      the IL-2 receptor was also undetectable, while mRNA for TNF-alpha, IL-1 beta and
      IL-6 were only marginally decreased. Histological evaluation of the infected
      lungs performed in parallel revealed dense mononuclear infiltrations around small
      bronchi and small blood vessels in control reinfected mice. In contrast, in CD4+
      T cell-depleted mice, these focal accumulation of lung tissue infiltrating cells
      were found to be greatly reduced. The data indicate that the inflammatory
      response in lung tissue thought to be mainly responsible for Mycoplasma
      pneumoniae disease is associated with an increased level and a prolonged
      expression of proinflammatory cytokines due to CD4+ lung infiltrating T cells.

PMID- 9145336
TI  - A call to looms.

PMID- 9145335
TI  - Differential expression of protein kinase C isozymes and small GTP-binding
      proteins during HL60 cell differentiation by retinoic acid and cyclic AMP:
      relation with phospholipase D (PLD) activation.
AB  - The differential expression of protein kinase C (PKC) isozymes and small GTP
      binding proteins, and their relation to O2 generation and phospholipase D (PLD)
      activation were analyzed during the differentiation of human promyelocytic HL60
      cells to neutrophil-like cells induced by either retinoic acid (RA) or dibutyryl
      cyclic AMP (dbcAMP). In response to either one of the inducers, nitroblue
      tetrazolium (NBT) reduction activity time-dependently increased. Although PLD
      activity was upregulated by dbcAMP-treatment, only a slight increase was observed
      in RA-treated cells. Small GTP-binding proteins Rac1, Rap1, and RhoA, which are
      reported to be implicated in O2- generation or PLD activation, were already
      expressed in undifferentiated HL60 cells and their significant changes were not
      detected during differentiation. The mRNAs of the cytosolic components of NADPH
      oxidase system, p47phox and p67phox, were present in trace amounts in
      undifferentiated cells. However, they rapidly increased in response to RA or
      dbcAMP. In response to either RA or dbcAMP, the increases were observed in cPKC
      isozymes (alpha, beta I, beta II) but not in other subtypes (delta, epsilon,
      theta, zeta) by both RT-PCR and Western blot analyses. In dbcAMP-treated cells
      PKC alpha increased remarkably, whereas PKC beta I and beta II mainly elevated in
      RA-treated cells. These results suggest the possibility that cPKCs are closely
      related to cell differentiation and that PKC alpha is involved in PLD activation.

PMID- 9145338
TI  - The development of students' perceptions of effective teaching: the ideal, best
      and poorest clinical teacher in nursing.
AB  - This article attempts to study students' perceptions of effective clinical
      teacher in nursing. To do this, 123 students from three schools with different
      curricula identified the important characteristics of a clinical teacher, using a
      modified NCTEI instrument. Then each respondent assessed to what extent her or
      his best and poorest clinical teachers possess these characteristics. The profile
      of an effective clinical teacher which emerged places the highest weight on the
      nursing competencies of the teacher and downplays both interpersonal
      relationships and personality traits. Differences between 2nd and 3rd year
      students were found in the placement of teaching skills and evaluation
      characteristics. No differences were disclosed among the compared schools.
      Conflicting research findings are analyzed. The results strongly suggest that the
      image of the ideal clinical teacher is not rooted in an existing teacher figure.
      The possible implications of the findings on the role model function of the
      clinical teacher are discussed.

PMID- 9145337
TI  - The negotiated order of clinical teaching.
AB  - The clinical teacher and students in traditional nursing education programs
      represent a temporary system within the permanent culture of the clinical area in
      which they teach. Temporary systems are a set of diversely skilled people working
      together on a complex task over a limited period of time. A member of a temporary
      system struggles to maintain a differentiated identity within the permanent
      system, while at the same time seeking a sense of collegiality and belonging.
      Clinical teachers experience a feeling of being somewhat akin to the nursing
      staff in the clinical area in which they teach because they are nurses. At the
      same time, clinical teachers are alienated from the nurses because the staff has
      developed a permanent structure that excludes clinical teachers from many aspects
      of nurses' working lives. The focus of research concerning clinical teaching has
      been the tasks assigned to the clinical teacher rather than the experience of
      teachers as members of a temporary system. This article presents one aspect of a
      year-long exploratory and descriptive qualitative research study designed to
      explore and describe what takes place in the realm of clinical teaching in
      nursing education. The discussion will focus on the experience of clinical
      teachers as temporary systems according to the sociological framework of
      negotiated order.

PMID- 9145339
TI  - The effect of a clinical practicum on undergraduate nursing students' self
      efficacy for community-based family nursing practice.
AB  - Providing family nursing care using a collaborative practice model presents a
      challenge to undergraduate students and to faculty who structure their learning
      experiences. A pre-test-post-test design was used to assess the impact of a 13
      week family nursing clinical practicum on the perceived self-efficacy of two
      groups of nursing students in three areas: knowledge related to family nursing,
      home visiting, and collaborative practice. Students completed the Family Nursing
      Self-Efficacy Questionnaire (FNSE) at the beginning of the academic year and 4
      and 8 months later to coincide with the timing of the practicum for each group
      (fall or winter term). A two-factor repeated measures analysis of variance
      (ANOVA) revealed a significant group X time effect (lambda = .80, p < .001).
      Students' self-efficacy differed significantly by group at time 2 only (t = 4.3,
      p < .001), supporting the positive effects of the clinical practicum on students'
      self-efficacy. Consistent with Bandura's (1977, 1986) theory, students rated
      actual performance of family nursing skills in a clinical setting as the most
      important source of efficacy information. Implications for designing meaningful
      clinical experiences in family nursing are discussed.

PMID- 9145340
TI  - The preceptor model of clinical instruction: the lived experiences of students,
      preceptors, and faculty-of-record.
AB  - The preceptor model of clinical instruction will become increasingly popular due
      to the cost of undergraduate education, the scholarly demands of research and
      teaching, and an interest in developing new partnerships among students,
      clinicians, and teachers. It is quite timely, therefore, that nurse researchers
      reveal the nature and utility of this instructional model prior to its widespread
      use. To that end, hermeneutic interviews (N = 31) were conducted with senior
      level undergraduate nursing students (n = 10), staff nurse preceptors (n = 11),
      and master's and PhD-prepared faculty-of-record (n = 10). Employing interpretive
      phenomenology, the authors identified common meanings, relational themes, and a
      constitutive pattern designated learning nursing thinking. An examination of this
      pattern and its associated themes may help identify those teaching practices that
      should be extended and those that should be altered.

PMID- 9145341
TI  - Differences in stress and challenge in clinical practice among ADN and BSN
      students in varying clinical courses.
AB  - There is limited research on student perceptions of their clinical experiences
      particularly in different clinical courses and settings. The purpose of this
      study was to examine the degree of stress, challenge, and threat associated with
      clinical practice experiences among ADN and BSN nursing students enrolled in
      various clinical courses and settings. The Pagana Clinical Stress Questionnaire
      was used to assess the clinical experiences of 416 undergraduate nursing students
      from 10 randomly selected associate degree (ADN) and baccalaureate (BSN) programs
      in the midwest. Significant differences were found across clinical courses
      (F[5,399] = 9.58, p < .0001) and settings (F[2,386] = 4.63, p = .01) in terms of
      students' stress. Stress was highest for students enrolled in pediatric nursing
      courses. ANOVA indicated significant differences across clinical courses in the
      degree of challenge and threat experienced by students. There were no differences
      in any of the variables studied when students had faculty from the nursing
      program or preceptors from the clinical setting as their teachers.

PMID- 9145342
TI  - Make-believe hospital--a pediatric clinical experience.

PMID- 9145343
TI  - Establishing camps as clinical sites.

PMID- 9145344
TI  - Enhancing the clinical practicum experience through journal writing.
AB  - Although journaling is commonplace, its usefulness or effectiveness has been
      rarely supported by empirical data or examples. The purpose of this article is to
      highlight integration of classroom and clinical learning, decision-making skills
      and level of skill acquisition in the Senior Practicum experiences through
      student journal entry exemplars. Critical thinking, observation and description,
      and empathy and release of feelings will be discussed.

PMID- 9145345
TI  - High frequency ventilation.
AB  - The 1990s have seen a dramatic resurgence of interest in high frequency
      ventilation (HFV). The role of HFV in the rescue of infants failing conventional
      mechanical ventilation (CMV) is now relatively well established. However, the
      wider role of HFV in the routine management of respiratory failure in the newborn
      is more contentious. Recent trials in small numbers of infants suggest that HFV
      may be associated with significantly less chronic lung disease than CMV when used
      under optimal conditions (i.e. with a 'high-volume' strategy, from early in the
      disease and continued to the point of weaning). Further, clinical trials are now
      required to define the role of HFV more clearly.

PMID- 9145347
TI  - Progressive myoclonic epilepsies: recent genetic advances.
AB  - The progressive myoclonic epilepsies are a rare group of debilitating epileptic
      encephalopathies characterized by myoclonic seizures, progressive neurological
      dysfunction and dementia. In the past year advances in gene mapping have isolated
      gene loci for the majority of progressive myoclonic disorders, paving the way for
      specific diagnosis, more accurate prognosis and risk calculation, as well as
      opening the potential for prenatal and pre-symptomatic diagnosis in at risk
      families.

PMID- 9145346
TI  - Chronic illness in adolescents: transfer or transition to adult services?
AB  - It is widely believed that the improved survival of young people with chronic
      diseases will be associated with the development of appropriate services within
      the adult healthcare domain. There is, however, little evidence to suggest that
      this is happening at a rate commensurate with clinical requirements. This paper
      highlights the multiplicity of barriers that impede the development of transition
      services to facilitate the transfer of medical care from the paediatric to the
      adult domain. Different models of transition care are described, and the terms
      'transfer' and 'transition' are differentiated. The clinical demand for service
      development is highlighted, as well as the need for specific research in this
      area of healthcare delivery.

PMID- 9145348
TI  - Outcome for tiny babies beyond the nursery.

PMID- 9145349
TI  - A follow-up study of infants < or = 2000 g birthweight treated in central
      Queensland.
AB  - OBJECTIVE: This follow-up study was undertaken in an effort to ascertain the
      morbidity in the survivors of infants < or = 2000 g birthweight cared for in the
      two Rockhampton intensive care nurseries. METHODOLOGY: The records of all infants
      < or = 2000 g delivered in or transferred to Rockhampton during the 11 year
      period 1979 through 1989 inclusive were extracted. Efforts were made to contact
      and examine all of these children. Those found to be disabled were assessed as
      being mildly, moderately or severely affected. RESULTS: Of the 482 infants of
      birthweight < or = 2000 g treated in the period under review, 393 survived to be
      discharged from hospital. Eight were known to have died subsequently. Of the
      remaining 385 children, 288 (74.8%) were able to be contacted and their health
      status determined. A total of 36 infants were found to have significant
      disabilities. Twenty-four were mildly affected, five moderately and seven
      severely affected. Severe disability in infants of < or = 1000 g was 16% (3/19).
      CONCLUSIONS: The incidence of disability was established in 74.8% of the
      surviving population. It was not dissimilar to the incidence of disability in
      similar birthweight groups in some Australian tertiary centres for the years
      under study. It is emphasized that the follow-up was incomplete and recognized
      that the survival rates and incidence of disability in survivors has improved in
      tertiary centres since the time frame of this study.

PMID- 9145350
TI  - Chronic lung disease in very low birthweight infants: a 5-year review.
AB  - OBJECTIVES: To determine the incidence, clinical spectrum and outcome of very low
      birthweight (VLBW) infants with chronic lung disease (CLD), and evaluate
      associated factors. METHODOLOGY: Retrospective review of 265 VLBW infants managed
      in the NICU from January 1988 to December 1992. RESULTS: The overall neonatal
      survival rate for VLBW infants was 83%. Sixty-five (25%) infants had CLD, of whom
      42% had severe CLD. Mortality in infants with CLD was 11%. In contrast with
      infants without CLD, CLD infants had significantly higher risk of adverse
      neurodevelopment with cerebral palsy documented in 13.5% and functional
      disability recorded in 34.6% at 2 years corrected age. Factors associated with
      the development of CLD included; decreasing birthweight (OR 0.98, CI 0.97-0.99),
      septicaemia (OR 4.96, CI 1.57-15.65), necrotizing enterocolitis (OR 119.07, CI
      4.98-2845.04), hyaline membrane disease (OR 5.34, CI 1.83-15.55), patent ductus
      arteriosus (OR 4.46, CI 1.75-11.36) and increasing fraction of inspired oxygen
      concentration in the first week of life (OR 1.09, CI 1.04-1.14). CONCLUSIONS:
      Chronic lung disease occurs frequently in VLBW infants and is associated with a
      high incidence of adverse neurodevelopment. Further studies to clarify the role
      of non-respiratory factors such as patent ductus arteriosus (PDA) and sepsis in
      the pathogenesis of CLD may reduce the incidence or prevent the development of
      CLD in these preterm infants.

PMID- 9145351
TI  - Chronic illness perception in adolescence: implications for the doctor-patient
      relationship.
AB  - OBJECTIVE: To describe the inter-relationship of chronic illness severity as
      perceived by adolescents with both psychosocial well-being and objective measures
      of illness severity. Additionally to compared the adolescents' perception of
      illness severity with how their physicians believe that the adolescents perceive
      their illness severity. METHODS: The psychological well-being of 48 adolescents
      with either cystic fibrosis (CF) or insulin-dependent diabetes mellitus (IDDM)
      was measured by four standardized questionnaires. The adolescents' perception of
      severity of illness was measured using an original instrument (PSCI), and this
      measure was compared to their physicians' estimates of how the adolescents
      perceived the severity of their illness and clinical illness. RESULTS: There were
      24 patients in both the CF and IDDM groups. Both groups were found to function
      well psychosocially; although, there were more patients with low self image
      compared to normative values. Depression and low self image were associated with
      a greater adolescent perception of illness severity. For both chronic illness
      groups, physicians' assessment of assumed adolescent perception of disease
      severity correlated with clinical indices of disease severity and was higher than
      the perception of illness severity reported by the adolescents. For adolescents
      with CF, but not with IDDM, perception of severity of chronic illness correlated
      with clinical indices. CONCLUSIONS: For adolescents with chronic illness, their
      perception of illness severity is an important indicator of psychosocial well
      being. Physicians do not accurately infer their patients' perception of illness
      severity.

PMID- 9145352
TI  - Emergency management skills of South Australian paediatric trainees.
AB  - OBJECTIVE: This article describes a theoretical and practical assessment of the
      emergency management skills of South Australian paediatric trainees. The aim was
      to identify strengths and weaknesses so as to optimally orientate future training
      in this area, and to provide a baseline that could be used to assess
      effectiveness of future interventions. METHODOLOGY: Thirty-four paediatric
      trainee medical officers responsible for after hours emergency care in Adelaide
      were asked to anonymously complete a 24 question theory assessment based on
      recognized emergency management training programmes, and to perform a mock
      clinical resuscitation. Response rate was 90% for the theoretical section and 69%
      for the practical. RESULTS: The average trainee was found to be deficient in one
      quarter to one third of the theoretical precepts, and required an average of 2
      min to establish effective bag-valve-mask ventilation with an infant manikin.
      CONCLUSIONS: There is a range of theoretical and practical resuscitation deficits
      that may currently hinder effective emergency management by paediatric trainees.

PMID- 9145353
TI  - Thyroid function in a population of children with attention deficit hyperactivity
      disorder.
AB  - OBJECTIVE: To determine the prevalence of thyroid hormone abnormalities and
      generalized resistance to thyroid hormone in a population of children with
      attention deficit hyperactivity disorder (ADHD) as compared to reference ranges
      determined from a control population and hence to determine if routine thyroid
      hormone screening in children with non-familial ADHD is indicated. METHOD:
      Children attending the State Child Development Centre in Perth, Western Australia
      with ADHD, as defined by the Diagnostic and Statistical Manual of Mental
      Disorders (fourth edition) provided the study population. The control population
      consisted of 353 normal children with a history of allergy in whom
      radioallergosorbent (RAST) testing was being performed. RESULTS: The prevalence
      of thyroid hormone abnormalities in the study population was 2.3% (95% CI 0.6%,
      5.7%). There were no cases of generalized resistance to thyroid hormone. The
      prevalence of thyroid hormone abnormalities in the general population of children
      and adolescents has been reported to vary between 1 and 3.7%. CONCLUSION: Routine
      thyroid hormone screening is not indicated in children with non-familial ADHD.

PMID- 9145354
TI  - Vigabatrin as first line therapy in infantile spasms: review of seven patients.
AB  - OBJECTIVE: To study the efficacy of vigabatrin as initial therapy in infantile
      spasms. METHODOLOGY: We reviewed seven patients with newly diagnosed infantile
      spasms referred to Tuen Mun Hospital, Hong Kong from 1994 to 1995. Vigabatrin was
      given as the initial monotherapy at therapeutic dose of 50-100 mg/kg. Efficacy
      was evaluated at the end of second week of treatment. RESULTS: Significant
      improvement was observed in four patients, 50-75% seizure reduction in two and no
      response in one patient. Efficacy was noted within the first week of treatment in
      five of the six patients who responded. No adverse effects were observed.
      Vigabatrin monotherapy could be continued in five patients. CONCLUSION:
      Vigabatrin could be considered as the first line treatment in infantile spasms. A
      period of 2 weeks may be sufficient to evaluate its efficacy.

PMID- 9145355
TI  - Perinatal outcome following conservative management of mid-trimester pre-labour
      rupture of the membranes.
AB  - OBJECTIVE: To assess perinatal outcome and the effect of antenatal steroid use
      following conservative management of 86 consecutive singleton pregnancies
      complicated by pre-labour rupture of membranes (ROM) in the mid-trimester (13-26
      weeks; mean 22.8 weeks). METHODOLOGY: Review of obstetric and neonatal case notes
      between 1 January 1990 and 31 December 1993. RESULTS: The duration of ruptured
      membranes (latent period) ranged from 1.25 to 105 days (mean 23.8 days; median 14
      days) and was inversely related to gestational age at ROM. There was clinical
      evidence of chorioamnionitis in 39.5% with placental histological changes
      consistent with chorioamnionitis in 76.6%. All infants were delivered before 33
      weeks gestation (mean 26 weeks). Overall, the mortality rate was 43.0% but 62.5%
      in infants with ROM before 24 completed weeks gestation. Adverse outcome (defined
      as death, severe intraventricular haemorrhage (IVH) or periventricular
      leucomalacia (PVL)) occurred in 46.5% and was significantly related to both
      gestation at delivery and gestation at ROM. In the group (n = 40) with ROM before
      24 weeks gestation, adverse outcome occurred in 65% and was inversely related to
      gestation at ROM independent of gestation at delivery. Antenatal steroid
      administration resulted in less adverse outcome independent of gestation at
      delivery (OR 0.31; 95% CI (0.09-0.98; P = 0.046)). CONCLUSION: From the neonatal
      perspective conservative management is justified for pregnancies with ROM at or
      after 24 weeks gestation; in this group the use of antenatal steroids prior to
      delivery may improve perinatal outcome. A poor outcome is associated with ROM
      that occurs before 24 weeks gestation.

PMID- 9145356
TI  - The overlap of attention deficit hyperactivity disorder with other common mental
      disorders.
AB  - OBJECTIVE: The literature on the overlap (co-morbidity) of attention deficit
      hyperactivity disorder (ADHD) with conduct disorder, specific learning
      disability, and anxiety disorders was reviewed to examine: (i) the evidence for
      ADHD being a syndrome distinct from the other conditions; and (ii) the evidence
      for co-morbid patterns representing meaningful subtypes of ADHD. METHODOLOGY:
      Narrative review of the literature. CONCLUSIONS: Conduct disorder is
      distinguished from ADHD by prognosis, patterns of association and familial
      aggregation. Pure' disorders are uncommon, however, and there is little evidence
      to support a distinct co-morbid subtype. There are few data that reliably
      distinguish ADHD from specific learning disabilities, but there are weaknesses in
      research to date. A specific ADHD+learning disabled subtype may exist, but as yet
      the implications for treatment are not known. Attention deficit hyperactivity
      disorder is distinguished from anxiety by symptom discrimination, factor
      analysis, patterns of association, familial aggregation and treatment response.
      There is evidence for a distinct ADHD+anxiety subtype.

PMID- 9145357
TI  - The immunogenicity of Haemophilus influenzae: meningococcal protein conjugate
      vaccine in Polynesian and non-Polynesian New Zealand infants.
AB  - OBJECTIVE: To examine the comparative immunogenicity of the Haemophilus
      influenzae type b-meningococcal protein (PRP-OMP) conjugate vaccine in Polynesian
      and non-Polynesian New Zealand infants. METHODOLOGY: Fifty-six Polynesian and 53
      non-Polynesian infants aged 2-7 months recruited from primary health care
      settings in Auckland received a two-dose primary series of PRP-OMP. A sub-sample
      of 83 participants received a booster dose of PRP-OMP at 12-16 months of age.
      Anti-PRP antibody concentrations were measured in pre- and post-vaccination blood
      samples. RESULTS: Antibody responses consistent with long-term protection (> or =
      1.00 microgram/mL) were observed in 72, 85 and 95% of children following the
      first, second and booster doses. CONCLUSIONS: Despite differences in disease
      epidemiology, PRP-OMP was highly immunogenic in Polynesian and non-Polynesian
      infants.

PMID- 9145358
TI  - Fat gram target to achieve high energy intake in cystic fibrosis.
AB  - OBJECTIVE: Higher fat and energy intakes confer a survival advantage in cystic
      fibrosis (CF). There is a need to develop effective nutrition programmes that
      ensure optimal energy intake in CF. METHODOLOGY: A cross-sectional measurement of
      clinical characteristics and energy and fat intakes in patients attending the CF
      outpatients clinic of the John Hunter Hospital, Newcastle was undertaken. Twenty
      nine subjects, mean age 12 years (range 4.3-20.2), completed weighed food records
      to determine the contribution of fat to the percentage of the recommended energy
      intake obtained and to document use of pancreatic enzyme replacement therapy.
      RESULTS: Diets with a high percentage of energy derived from fat did not
      guarantee that individuals with CF met their energy requirements. Subjects with
      total fat intakes of 100 g per day or greater, however, achieved in excess of
      110% recommended daily intake (RDI) for energy. Up to 47% of subjects consumed
      more pancreatic enzyme replacement capsules than shown to give maximum
      effectiveness. CONCLUSION: Setting a 100 g daily fat target is a realistic way of
      ensuring high energy intakes in CF. Fat ready reckoners would identify the fat
      content of food and prescribe specific numbers of pancreatic enzyme replacement
      capsules to be consumed with each meal or food item.

PMID- 9145359
TI  - Erythromycin treatment for gastrointestinal dysmotility in preterm infants.
AB  - OBJECTIVE: To report our clinical experience on the use of oral erythromycin for
      the treatment of severe gastrointestinal dysmotility in preterm infants.
      METHODOLOGY: A case series study of seven preterm infants (six were very low
      birthweight) with severe intestinal dysmotility in a tertiary neonatal centre.
      RESULTS: All responded favourably without adverse effects and tolerated full
      enteral feeding within 1-2 weeks of the commencement of the drug. CONCLUSIONS: As
      prolonged total parenteral nutrition carries significant risk of complications,
      this therapy could be considered in selected preterm infants who fail to
      establish enteral feeding after an extended period, and in whom an anatomically
      obstructive lesion of the gastrointestinal tract has been excluded. Meanwhile, we
      would caution against the widespread implementation of this therapeutic approach
      until formal evaluation by randomized controlled trials have established the
      exact role of erythromycin, or its analogues, in the treatment of intestinal
      dysmotility in preterm infants.

PMID- 9145360
TI  - Developmental dysplasia of the hip in South Australia in 1991: prevalence and
      risk factors.
AB  - OBJECTIVE: To determine the prevalence of developmental dysplasia of the hip
      (DDH) in South Australia (SA) in 1991, the proportion of cases detected in the
      neonatal period and the perinatal risk factors for DDH. METHODOLOGY: Cases of DDH
      born in SA in 1991 were identified from multiple sources and their clinical data
      linked to perinatal data provided by midwives; five controls per case were
      obtained randomly from SA livebirths without congenital abnormalities and
      adjusted odds ratios (OR) for potential risk factors obtained by logistic
      regression analysis. South Australia perinatal data were also used to estimate
      numbers of births with perinatal risk factors for targeted screening. RESULTS:
      Two hundred and six cases of isolated DDH were identified, giving a prevalence of
      10.5 per 1000 births. Of these, 173 (84%) had been detected in the neonatal
      period. The perinatal risk factors for DDH were identified as breech presentation
      (OR 9.65), female babies (OR 4.04), first births (OR 1.91) and maternal age of 25
      years or more (OR 1.53). Screening breech and firstborn female babies (23% of
      births) would yield approximately 51% of cases of DDH. CONCLUSIONS: Isolated DDH
      had a prevalence of 10.5 per 1000 births and 84% of cases had been detected in
      the neonatal period in SA. Repeated screening during infancy of "at risk' groups
      of babies is recommended.

PMID- 9145361
TI  - Longitudinal study of rotavirus infection in child-care centres.
AB  - OBJECTIVE: To describe the epidemiology of symptomatic and asymptomatic rotavirus
      infection among young children attending Sydney child-care centres during the
      1994 rotavirus season. METHODS: Children aged 0-36 months in 11 child-care
      centres participated in the study. A weekly stool specimen was collected from
      each subject and tested for rotavirus antigen by commercial enzyme immunoassay.
      RESULTS: One hundred and seventy-eight children (76 girls and 102 boys) with a
      mean age of 18.2 +/- 6.5 (SD) months were enrolled for a total of 2249 child
      weeks. Of 1653 weekly faecal specimens, 59 (3.6%) were positive for rotavirus
      antigen. Positivity for rotavirus antigen peaked at 8.0% and 7.4% of specimens in
      weeks 6 and 7, respectively. The 59 positive specimens were obtained from 44
      children in eight of the 11 study centres. One child appeared to suffer a second
      episode. Eighty-two per cent of episodes were associated with symptoms of
      gastroenteritis. Overall, 32% of the children in the eight affected centres were
      infected; 52% of those < 12 months were infected compared to 26% of older
      children. Secondary spread to household contacts was also documented.
      CONCLUSIONS: Rotavirus infection poses a significant health problem in under-3
      year-old children attending child-care centres in Sydney. We believe that these
      results are applicable to all Australian children of this age attending group
      child care.

PMID- 9145362
TI  - Outcome at 2 years of children 23-27 weeks' gestation born in Victoria in 1991
      92. The Victorian Infant Collaborative Study Group.
AB  - OBJECTIVE: To determine the survival and sensorineural disability rates in very
      preterm infants born in 1991-92, and to compare the results with contemporaneous
      normal birthweight controls and with preterm infants born in 1985-87.
      METHODOLOGY: This was a geographically determined cohort study in the state of
      Victoria, Australia of consecutive livebirths 23-27 weeks' gestational age born
      during 1991-92, and randomly selected contemporaneous normal birthweight (NBW)
      controls born during 1991-92 in the three level-III perinatal centres in the
      State. Consecutive livebirths 24-26 weeks gestational age born in the State
      during 1985-87 comprised another comparison group. The main outcome measures were
      survival and sensorineural disability rates at 2 years of age. RESULTS: Of the
      401 livebirths 23-27 weeks in 1991-92, 225 (56.1%) survived to 2 years of age.
      The survival rate for those 24-26 weeks was 57.4% (143/249), a statistically
      significant increase on the regional survival rate of 30.1% (95/316) in 1985-87.
      In 1991-92 births, the survival rate rose significantly with increasing
      gestational age, and was significantly higher than in 1985-87 at each of 24, 25,
      and 26 weeks. Of sensorineural impairments in preterm survivors at 2 years of
      age, the rate of blindness was significantly lower in 1991-92 (2.3%) compared
      with 1985-87 (8.4%), and the overall rates of sensorineural disability were not
      statistically different in 1991-92 compared with 1985-87. In 1991-92 preterm
      survivors, the survival rate free of disability rose significantly with
      increasing gestational age, and as a percentage of survivors the rate of
      disability overall fell with increasing gestational age. However, the rate of
      disability overall was much higher in preterm infants than NBW controls.
      CONCLUSIONS: Survival rates of very preterm infants in this regional cohort have
      improved in the 1990s after the introduction of exogenous surfactant. Blindness
      at 2 years of age was significantly lower than in an earlier preterm cohort, but
      the rates of sensorineural disability still remain higher in very preterm
      survivors than for NBW controls. Although survival rates are lower and disability
      rates are higher with diminishing maturity, there is no obvious gestational age
      below which adverse neurological outcome in survivors would preclude active
      management on the basis of gestational age alone.

PMID- 9145363
TI  - Megaloblastic anaemia and pancytopenia secondary to prophylactic cotrimoxazole
      therapy.

PMID- 9145364
TI  - Foramina parietalia permagna: report of nine cases in one family.
AB  - Nine members of a family with foramina parietalia permagna (FPP), inherited as an
      autosomal dominant trait are reported. Although usually benign, FPP may be
      associated with other malformations.

PMID- 9145365
TI  - V-shaped pillows and unsafe infant sleeping.
AB  - OBJECTIVE: To investigate the possibility that adult size V-shaped pillows may be
      associated with accidental asphyxial deaths in infants. METHODOLOGY: Review was
      undertaken of all cases of sudden infant death presenting to the Women's and
      Children's Hospital in Adelaide involving infants who had been found on adult
      size V-shaped pillows. RESULTS: Four cases of sudden infant death were found in
      which infants were found sleeping on V-shaped pillows. All of the deaths had
      occurred in 1995. In two of the cases the pillows were considered to be
      implicated in the cause of death as the potential for obstruction of the infants'
      airways could be demonstrated on death scene reconstruction. CONCLUSION: Adult
      size V-shaped pillows may be unsafe for use in small infants who may accidentally
      suffocate if trapped between the two arms, or under, the pillow. The use of such
      pillows to maintain the body position of sleeping infants should be discouraged.

PMID- 9145366
TI  - Social and educational outcome of rural children.

PMID- 9145367
TI  - Missing values ignored.

PMID- 9145369
TI  - Self-induced overdose of ADHD medication.

PMID- 9145368
TI  - The social and educational outcome of a cohort of rural children in relation to
      the racial and socioeconomic groupings of their parents.

PMID- 9145370
TI  - Paying attention to ADD.

PMID- 9145371
TI  - Tyrosine supplementation in phenylketonuria.

PMID- 9145372
TI  - Epstein-Barr virus associated parotitis.

PMID- 9145373
TI  - Treatment of congenital hypothyroidism.

PMID- 9145374
TI  - Toward understanding insulin fibrillation.
AB  - Formation of insulin fibrils is a physical process by which partially unfolded
      insulin molecules interact with each other to form linear aggregates. Shielding
      of hydrophobic domains is the main driving force for this process, but formation
      of intermolecular beta-sheet may further stabilize the fibrillar structure.
      Conformational displacement of the B-chain C-terminal with exposure of nonpolar,
      aliphatic core residues, including A2, A3, B11, and B15, plays a crucial role in
      the fibrillation process. Recent crystal analyses and molecular modeling studies
      have suggested that when insulin fibrillates this exposed domain interacts with a
      hydrophobic surface domain formed by the aliphatic residues A13, B6, B14, B17,
      and B18, normally buried when three insulin dimers form a hexamer. In rabbit
      immunization experiments, insulin fibrils did not elicit an increased immune
      response with respect to formation of IgG insulin antibodies when compared with
      native insulin. In contrast, the IgE response increased with increasing content
      of insulin in fibrillar form. Strategies and practical approaches to prevent
      insulin from forming fibrils are reviewed. Stabilization of the insulin hexameric
      structure and blockage of hydrophobic interfaces by addition of surfactants are
      the most effective means of counteracting insulin fibrillation.

PMID- 9145375
TI  - Isolation and structure elucidation of the major degradation products of cefaclor
      formed under aqueous acidic conditions.
AB  - The aqueous acidic degradation of the oral cephalosporin cefaclor was
      investigated. A number of degradation products were isolated and characterized.
      The degradation products can be loosely classified into three categories:
      thiazole derivatives, pyrazine derivatives, and simple hydrolysis or
      rearrangement products. Degradation pathways are proposed that involve (1)
      hydrolysis of the beta-lactam carbonyl with subsequent rearrangement, (2) ring
      contraction of the six-membered cephem nucleus to five-membered thiazole
      derivatives through an episulfonium ion intermediate, and (3) attack of the
      primary amine of the phenylglycyl side chain on the "masked aldehyde" at carbon-6
      to form fluorescent substituted pyrazines.

PMID- 9145376
TI  - Isolation and structure elucidation of the major degradation products of cefaclor
      in the solid state.
AB  - Cefaclor is a beta-lactam antibiotic that degrades slowly under normal storage
      conditions to several minor products. To obtain samples large enough to permit
      structure elucidation, cefaclor was allowed to degrade at 40 degrees C (75%
      relative humidity) and at 85 degrees C. The profile of degradation products
      formed under these conditions is qualitatively similar to the profile of
      degradation products observed in samples of cefaclor aged for 14 years at room
      temperature, although some products found in the sample degraded at 85 degrees C
      are not formed at the lower temperatures. Using preparative reversed-phase high
      performance liquid chromatography (rp-HPLC) and a combination of spectroscopic
      methods, we have isolated and characterized 17 of these degradation products.
      Some of these products were also isolated from studies of aqueous degradations.
      The major products appear to have arisen from five distinct pathways: (1)
      isomerization of the double bond in the dihydrothiazine ring; (2)
      decarboxylation; (3) ring contraction of the cephem nucleus to thiazole
      structures; (4) oxidative attack at carbon 4 of the dihydrothiazine ring; and (5)
      intramolecular attack of the primary amine of the side chain on either the beta
      lactam carbonyl to form 3-phenyl-2,5-diketopiperazines or the "masked aldehyde"
      at carbon 6 to form 2-hydroxy-3-phenylpyrazine derivatives. The pathway involving
      oxidation at carbon 4 is particularly important at ambient temperatures and is
      unique to the solid-state degradation.

PMID- 9145377
TI  - Pharmacokinetics of 1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1- piperazinyl)
      1,4-dihydro-4-oxoquinolone-3-carboxylic acid hydrochloride (DW-116), a new
      quinolone antibiotic in rats.
AB  - The objectives of this study were to characterize the pharmacokinetics of 1-5
      fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1- piperazinyl)-1,4-dihydro-4-oxoquinolone
      3-carboxylic acid hydrochloride (DW-116), a newly developed quinolone antibiotic,
      and to compare these kinetics with those of ciprofloxacin and rufloxacin,
      representative quinolone antibiotics, in rats. Rats were subjected to surgery
      involving catheterization of the femoral vein and artery. DW-116 (4, 20, or 200
      mg/kg), ciprofloxacin (20 mg/kg), or rufloxacin (20 mg/kg) was administered
      either intravenously (iv) or orally. Blood samples were collected at various
      times and subjected to an HPLC assay for the quinolones. Temporal profiles of
      plasma concentration after iv administrations of DW-116 at doses of 4, 20, and
      200 mg/kg exhibited an apparent multiexponential decline. In the three doses
      examined, systemic clearance and steady-state volume of distribution of DW-116,
      calculated by model-independent methods, were in the range 0.17 approximately
      0.23 L/h/kg and 2.90 approximately 4.44 L/kg, respectively. When DW-116 was given
      orally at doses of 4, 20, or 200 mg/kg, the AUC values were nearly identical to
      those following iv administration, indicating an almost complete absorption
      (i.e., the percent bioavailability was 90.0 for 4 mg/kg, 99.0 for 20 mg/kg, and
      98.3 for 200 mg/kg) in the dose range examined. The absorption of DW-116 appears
      to be extremely rapid because the mean residence time calculated from the oral
      administration data was not significantly different from that for the iv
      administration. At a dose of 20 mg/kg, the mean residence time for iv
      administered ciprofloxacin and rufloxacin was smaller than that of DW-116,
      indicating that DW-116 remains in the body longer than the other quinolones.
      Absolute percent bioavailabilities of ciprofloxacin (69.9%) and rufloxacin
      (84.9%) were smaller than that obtained for DW-116 (99.0%). Because it has been
      reported that the in vivo antibacterial activity of DW-116 is comparable or
      superior to that of rufloxacin and ciprofloxacin, despite the fact that the in
      vitro activity is significantly lower, the pharmacokinetics of this antibiotic
      may be responsible, at least in part, for the enhanced in vivo antibacterial
      activity of DW-116.

PMID- 9145378
TI  - In vivo evaluation of zidovudine (AZT)-loaded ethylcellulose microspheres after
      oral administration in beagle dogs.
AB  - The purpose of this study was to evaluate the in vivo performance of sustained
      release zidovudine (AZT) microspheres after oral administration in Beagle dogs,
      and to establish an in vitro-in vivo correlation. Two AZT microsphere
      formulations as well as AZT powder were administered to four Beagle dogs. Plasma
      samples were analyzed by HPLC. The plasma concentration-time data was analyzed by
      both compartmental and noncompartmental pharmacokinetic analyses. Based on the
      calculated pharmacokinetic parameters, in vivo release profiles were simulated
      and compared with in vitro release profiles in three different release media.
      Significantly longer mean residence time (MRT) was observed after administration
      of the sustained-release microspheres compared with AZT powder. Significantly
      lower maximum (Cmax) concentration values and longer times to Cmax (tmax) values
      were also observed. Formulation I showed the longest MRT (4.4 h). AZT plasma
      concentration was maintained above the minimum effective concentration for
      approximately 10 h after administration of Formulation I. The relative
      bioavailability of the microsphere formulations with respect to AZT powder was
      not significantly different from 1. The in vitro release of the three
      formulations was slower in simulated gastric fluid compared with simulated
      intestinal fluid. The addition of enzymes and mucin to the release media
      significantly lowered the in vitro release rate of AZT from the microspheres
      formulations, but not from AZT powder. A good level of in vitro-in vivo
      correlation (Level A correlation) was achieved with a release medium that was
      composed of simulated gastric fluid with pepsin and mucin for 2 h followed by
      simulated intestinal fluid with pancreatin and mucin for 8 h. This in vitro model
      may be used to predict the in vivo release of AZT, in the further development of
      controlled-release AZT formulations.

PMID- 9145379
TI  - Stereoselective pharmacokinetics of bisoprolol after intravenous and oral
      administration in beagle dogs.
AB  - The stereoselective pharmacokinetics of bisoprolol, a highly beta 1-selective
      adrenoceptor blocking agent, was studied in dogs. After intravenous and oral
      administration of the racemate, there was a difference in the plasma
      concentration between S(-)- and R(+)-bisoprolol. The area under the curve (AUC)
      of concentration versus time of S(-)-bisoprolol was approximately 1.5 times
      higher than that of R(+)-bisoprolol and the elimination half-life of S(-)
      bisoprolol was approximately 1.4 times longer than that of R(+)-bisoprolol.
      However, no differences were observed in the volume of distribution, absolute
      bioavailability, and renal clearance between the two enantiomers. The plasma
      protein binding of S(-)-bisoprolol was also the same as that of the R(-)-isomer.
      No chiral inversion or enantiomer-enantiomer interaction was observed, when
      enantiomers were solely administered via the intravenous route. The comparison of
      the oxidative metabolic rate of two enantiomers using dog liver microsomes
      demonstrated that the metabolite was more slowly formed from S(-)- than from R(+)
      bisoprolol. Consequently, we concluded that the stereoselective difference in the
      metabolic clearance between S(-)- and R(+)-bisoprolol caused the difference in
      the disposition of bisoprolol enantiomers.

PMID- 9145380
TI  - Gentamicin-loaded hydraulic calcium phosphate bone cement as antibiotic delivery
      system.
AB  - A hydraulic calcium phosphate cement made of beta-tricalcium phosphate [beta
      Ca3(PO4)2], monocalcium phosphate monohydrate [Ca(H2PO4)2-H2O], and water was
      used as a delivery system for the antibiotic gentamicin sulfate (GS). GS, added
      as powder or as aqueous solution, was very beneficial to the physicochemical
      properties of the cement. The setting time increased from 2 to 4.5 min with 3%
      (w/w) GS and then slowly decreased to 3.75 min with 16% (w/w) GS. The tensile
      strength increased from 0.4 to 1.6 MPa with 16% (w/w) GS. These effects were
      attributed to the presence of sulfate ions in GS. The release of GS from the
      cement was measured in a pH 7.4 phosphate-buffered saline solution at 37 degrees
      C by USP paddle method. Factors such as cement porosity, GS content and presence
      of sulfate ions or polymeric additives were investigated. The amount of GS
      released was roughly proportional to the square root of time up to approximately
      50% release. Afterwards, the release rate markedly slowed down to zero. In all
      but two cement formulations, the total dose of GS was released within 7 days,
      indicating that no irreversible binding occurred between the cement paste and the
      antibiotic. When small amounts of hydroxypropylcellulose or poly(acrylic acid)
      were added to the cement, the maximum fraction released was a few percent lower
      than the total GS dose, suggesting some binding between the polymer and GS. The
      GS release rate was strongly influenced by the presence of sulfate ions in the
      cement paste and by the cement porosity. The higher the sulfate ion content of
      the cement paste, the lowe the GS release rate. This influence was attributed to
      the finer cement micro-structure induced by the presence of sulfate ions.
      Furthermore, when the initial cement porosity was increased from 38 to 69%, the
      release rate almost tripled (0.16 to 0.45 h-1/2). Finally, the biological
      activity of GS in the cement was maintained, as measured by assaying the release
      medium.

PMID- 9145381
TI  - Importance of sebaceous glands in cutaneous penetration of an antiandrogen:
      target effect of liposomes.
AB  - The significance of the sebaceous gland pathway in the cutaneous permeation of an
      antiandrogen, 4-[3-(4-hydroxybutyl)-4,4-dimethyl -2,5-dioxo-1-imidazolidinyl]-2
      (trifluoromethyl)benzonitrile (RU 58841), was studied with normal hairless rat
      skin and an induced scar hairless rat skin without sebaceous glands. RU 58841 was
      dissolved in an alcoholic solution and encapsulated in liposomes for comparison.
      After 24 h, the cumulative percentage of RU 58841 absorbed in vitro was 3-4-fold
      higher in the normal skin than in the scar skin; in the case of liposomes, the
      accumulation of the drug in the normal dermis was significantly higher than in
      the scar one. In the in vivo cutaneous distribution, the epidermis and dermis of
      the normal skin contained higher amounts of RU 58841 than the scar skin (ninefold
      with the solution and 16-fold with liposomes). An autoradiography study showed
      that with the solution, the drug was mainly localized in the stratum
      corneum/epidermis, and with the liposomes, the drug was mainly localized in the
      sebaceous glands. We concluded that the sebaceous glands constituted the main
      pathway for RU 58841. The alcoholic solution encouraged the localization of the
      drug into the stratum corneum, whereas liposomes targeted the sebaceous glands.

PMID- 9145382
TI  - A comparative computer simulation study of three different sparse-sampling
      methods for the estimation of steady-state area under the concentration-time
      curve (AUC) and maximum concentration (Cmax) in toxicokinetics.
AB  - A limited-sampling method is proposed to estimate the area under the curve (AUC)
      of concentration versus time and maximum concentration (Cmax) following single or
      multiple oral doses of a hypothetical drug. The plasma concentration versus time
      data sets for 50 animals were generated by simulation. The limited-sampling model
      (LSM) was developed with samples from 10 animals at a single time point. The
      model was validated in another 40 animals who received either a 500-mg single
      dose or multiple doses orally. The model provided good population mean estimates
      of AUC and Cmax. The proposed method was compared with the existing two methods;
      they are, naive sampling (five time points) and optimal sampling (three time
      points). The method described here may be useful in estimating AUC and Cmax with
      one or two samples in toxicokinetic studies following single or multiple oral
      dosing without detailed pharmacokinetic studies.

PMID- 9145383
TI  - Integration of in vitro data into allometric scaling to predict hepatic metabolic
      clearance in man: application to 10 extensively metabolized drugs.
AB  - In this study, we investigated rational and reliable methods of using animal data
      to predict in humans the clearance of drugs which are mainly eliminated through
      hepatic metabolism. For 10 extensively metabolized compounds, adjusting the in
      vivo clearance in the different animal species for the relative rates of
      metabolism in vitro dramatically improved the predictions of human clearance
      compared to the approach in which clearance is directly extrapolated using body
      weight. Using hepatocyte data to normalize the in vivo clearances led to lower
      median deviations between the observed and predicted clearances in man compared
      to the approach normalizing data with brain weight (30-40% vs 60-80%,
      respectively). In addition, the approach integrating in vitro data appeared to be
      superior with respect to the range of deviations: approximately 2-fold
      underestimation, in the worst case, was observed by using in vitro data, whereas
      normalizing data by brain weight led to up to 10-fold underestimation of
      clearance in man. In addition, the integration of in vitro data provides a more
      rational basis to predict the metabolic clearance in man and may be applicable to
      compounds undergoing phase I and phase II metabolism as well.

PMID- 9145384
TI  - Absorption, distribution and excretion of GT31-104, a novel bile acid
      sequestrant, in rats and dogs after acute and subchronic administration.
AB  - The absorption, distribution, and excretion of GT31-104, a novel bile acid
      sequestrant, was studied in rats and dogs after both acute and subchronic oral
      administration. The polyallylamine backbone of GT31-104 was labeled with tritium
      and one of the alkyl side chains was labeled with 14C. The mean blood and plasma
      concentration of [3H, 14C]GT31-104 in rats, in both treatment regimens, was
      negligible at all time points, with the highest amount observed being 0.69
      microgram eq/g blood; in dogs the mean blood and plasma concentration of [3H,
      14C]GT31-104 was below the limit of quantitation (< 0.001% total dose) at all
      time points. In both rats and dogs, the mean total urinary excretion of [3H,
      14C]GT31-104 was approximately 0.06% of the total dose. The fecal excretion data
      indicates that both 3H- and 14C-derived radioactivity was excreted entirely in
      the feces. Mean total radioactivity excreted in the feces ranged from
      approximately 95 to 105% in the rats and 92 to 102% in the dogs. Across the
      different treatment regimens, in both species, tissue concentrations were
      negligible (< 0.01% total dose) and no differences in tissue profile were noted,
      indicating that there was no effect of pretreatment on [3H, 14C]GT31-104
      absorption. GT31-104 was extracted with water, and the water-soluble portion
      contained radioactivity that would correlate to approximately 0.19% of the 3H
      dose and 0.41% of the 14C dose; this portion probably accounted for the
      negligible radioactivity observed systemically. Analysis of gastrointestinal (GI)
      tract tissues with contents indicated that GT31-104 is rapidly cleared from the
      GI tract. These data indicate that GT31-104 is not absorbed from the GI tract in
      rats and dogs.

PMID- 9145385
TI  - Molecular determinants of recognition for the intestinal peptide carrier.
AB  - Computer-aided conformational analysis was used to characterize the pharmacophore
      for the intestinal peptide carrier. The active analog approach to pharmacophore
      building was applied as implemented in the SYBYL software package. Conformational
      analysis and MOPAC calculations were used to determine the lowest energy
      conformation of carrier substrates, as well as the conformations of compounds
      that displayed a common pharmacophoric geometry (i.e., inhibitors and inactive
      structural analogs). A pharmacophore map was calculated, and based on structural
      mutualities and functional topology, three substrate groups were suggested:
      compounds that bind to the transporter and are transferred across the membrane;
      compounds that show affinity for the peptide carrier (i.e., known to inhibit
      transport of substrates) but are not transferred across the membrane; and
      compounds that contain the pharmacophoric geometry but show no affinity for the
      carrier. Affinity for the peptide transporter can be diminished or abolished in
      either of three ways: esterification of the free carboxylic acid moiety;
      introduction of a second negative group; and intramolecular steric hindrance of
      the free carboxylic acid by either side chains with a positively charged nitrogen
      function or groups capable of hydrogen bond formation.

PMID- 9145386
TI  - Preparation and stabilization of heparin/gelatin complex coacervate
      microcapsules.
AB  - The aims of this study are to optimize conditions for the preparation,
      stabilization, and harvesting of heparin/gelatin microcapsules prepared by
      complex coacervation. Microelectrophoresis and dry coacervate weight were used to
      determine the optimum conditions of pH and ionic strength for maximum
      heparin/gelatin coacervate yield. Heparin/gelatin microcapsules were formed by
      complex coacervation in the presence and absence of poly(1-vinyl-2-pyrrolidone)
      (PVP), which was used as a stabilizer. The microcapsules were collected using a
      spray-drying technique. Microcapsule particle size was analyzed using an
      AccuSizer optical sizer. Optimized conditions for maximum coacervate yield were
      pH 2.6, ionic strength 10 mM, and a 1:2 heparin/gelatin A ratio. PVP stabilized
      the heparin/gelatin coacervate droplets and reduced droplet aggregation during
      spray-drying. The mean particle diameter of the spray-dried coacervate droplets
      was lower in the presence of PVP and was unaffected by PVP concentration (in the
      range 0.5-2.0% w/w). Heparin/gelatin microcapsules, prepared under conditions
      optimized for maximum coacervate yield, were stabilized without the use of
      chemical cross-linking agents. Stabilization was achieved by a combination of the
      addition of PVP and spray-drying.

PMID- 9145387
TI  - Studies on the interaction between water and (hydroxypropyl)methylcellulose.
AB  - The moisture sorption and desorption profiles of four different viscosity grades
      of (hydroxypropyl)methylcellulose (HPMC) 2208 (HPMC K100, HPMC K4M, HPMC K15M,
      and HPMC K100M) of different particle size fractions were analyzed according to
      the Young and Nelson equations. These equations describe three locations of the
      sorbed moisture: monolayer adsorption, externally adsorbed moisture, and
      internally absorbed moisture. The effects of particle size and viscosity grade of
      HPMC on the three locations of moisture showed that an increase in particle size
      generally resulted in a reduction in the amount of internal absorption and an
      increase in the amount of external adsorption. These changes were more apparent
      for HPMC K100 and HPMC K4M than for the higher viscosity grades. The lowest
      values of internally absorbed moisture were obtained for HPMC K100M. Changes in
      tensile strengths, mean yield pressures, and elastic recoveries of HPMC K4M
      tablets were explained in terms of the changes produced in the internally
      absorbed moisture and the externally adsorbed moisture. The amounts of
      nonfreezing and freezing water in samples exposed to moisture were determined
      from melting endotherms obtained by differential scanning calorimetry. Increases
      in the water:HPMC ratio resulted in increases in the enthalpies of water melting
      for the four viscosity grades of HPMC for the < 45 and 250-350 microns particle
      size fractions. The amount of nonfreezable water was unaffected by change in
      viscosity grade or particle size.

PMID- 9145388
TI  - Effect of hexadecyltrimethylammonium bromide-based microemulsions on the rate of
      decomposition of the beta-lactam antibiotic cephaclor.
AB  - Microemulsions of hexadecyltrimethylammonium bromide (HTAB)/n
      butanol/hexadecane/water catalyze the intramolecular degradation of cephaclor.
      The rate increase is a sensitive function of the microemulsion volume fraction
      and salt concentration. The effects of microemulsions, analyzed quantitatively
      using a pseudophase ion-exchange model, assumed that the extent of ion
      dissociation from the microemulsions varies with volume fraction. Comparison of
      micellar and microemulsion effects on the same reaction shows that microemulsions
      are less effective catalysts. Acceleration decreased significantly by increasing
      the relative proportion of n-butanol ratio in microemulsions and by addition of n
      butanol in HTAB micelles. Comparison of the activation parameters of the reaction
      in aqueous solution, microemulsions, and micelles suggests that catalysis by both
      aggregates is driven mainly by entropic contributions.

PMID- 9145389
TI  - Averaging pharmacokinetic parameter estimates from experimental studies:
      statistical theory and application.
AB  - In most experimental pharmacokinetic studies, parameter estimates are computed
      separately for each subject, then averaged across subjects. Average estimators
      for ratios and functions of parameters are often of interest; examples include
      half-life and clearance. For these parameters, recommendations regarding
      averaging using the arithmetic versus the harmonic mean have been based on
      computer simulations.1-3 The goal in this paper was to demonstrate that these
      empirically generated results can be derived using approximations for the
      expected values of reciprocals and ratios. We first consider estimating the
      reciprocal of a parameter, and predict the earlier simulation results for half
      life. We additionally predict results for clearance when computed as dose divided
      by area under the curve. Next we consider estimating the ratio of two parameters,
      and predict the earlier simulation results for clearance in a first-order
      exponential model. As a further example, we predict results for the mean
      residence time in noncompartmental analysis. These approximations provide a
      unifying approach that can be used to determine optimal summary estimators,
      without the need for extensive computer simulations.

PMID- 9145390
TI  - Molecular structure and gas chromatographic retention behavior of the components
      of Ylang-Ylang oil.
AB  - Using quantitative structure-retention relationships (QSRR) methodologies the
      Kovats gas chromatographic retention indices for both apolar (DB-1) and polar (DB
      Wax) columns for 48 compounds from Ylang-Ylang essential oil were empirically
      predicted from calculated and experimental data on molecular structure.
      Topological, geometric, and electronic descriptors were obtained for model
      generation. Relationships between descriptors and the retention data reported
      were established by linear multiple regression, giving equations that can be used
      to predict the Kovats indices for compounds present in essential oils, both in DB
      1 and DB-Wax columns. Factor analysis was performed to interpret the meaning of
      the descriptors included in the models. The prediction model for the DB-1 column
      includes descriptors such as Randic's first-order connectivity index (1X), the
      molecular surface (MSA), the sum of the atomic charge on all the hydrogens (QH),
      Randic's third-order connectivity index (3X) and the molecular electronegativity
      (chi). The prediction model for the DB-Wax column includes the first three
      descriptors mentioned for the DB-1 column (1X, MSA and QH) and the most negative
      charge (MNC), the global softness (S), and the difference between Randic's and
      Kier and Hall's third-order connectivity indexes (3X-3XV).

PMID- 9145391
TI  - Identification of chlorothiazide and hydrochlorothiazide UV-A photolytic
      decomposition products.
AB  - Methanol solutions of hydrochlorothiazide and chlorothiazide were irradiated with
      fluorescent UV-A lamps in order to simulate degradation under normal conditions.
      The degradation products were identified by comparison to synthetic standards
      featuring electrospray ionization mass spectroscopy, ultraviolet spectroscopy,
      and high performance liquid chromatography. The standards were characterized by
      high resolution fast atom bombardment MS and 1H NMR. The photolysis of
      chlorothiazide resulted in photodehalogenation products exclusively, while the
      irradiation of hydrochlorothiazide primarily yielded photodehalogenation products
      with significant yields of photodehydrogenation products and minor amounts of
      thermal hydrolysis products.

PMID- 9145393
TI  - Adsorption of fluoxetine HCl by activated charcoal.
AB  - We studied the adsorption of fluoxetine HCl (Prozac) by Norit USP XXIII activated
      charcoal in vitro, in simulated gastric fluid (USP; pH 1.2), and in simulated
      intestinal fluid (USP; pH 7.5). The data were fitted to both Langmuir and
      Freundlich equations. The Langmuir Qm values (maximal adsorption capacities) for
      pH 1.2 and 7.5 were 0.258 and 0.330 g drug/g charcoal, respectively. These
      excellent capacities suggest that oral charcoal therapy would be effective for
      fluoxetine overdose.

PMID- 9145392
TI  - Liposome-encapsulated ampicillin: physicochemical and antibacterial properties.
AB  - The objectives of this study were to develop high-performance liquid
      chromatography (HPLC) and antibacterial assays for ampicillin encapsulated in
      multilamellar liposomes (MLV) and investigate the physicochemical and
      antibacterial properties of ampicillin-liposome systems. The major findings were
      fourfold. First, ammonium acetate (0.575%) in methanol:water (450:550; v/v),
      adjusted to pH 7.2, was suitable as the mobile phase for the HPLC determinations
      of ampicillin in both aqueous and liposomal systems. This mobile phase also
      provided (alone or with additional methanol) complete dissolution of liposomal
      assay samples in a precolumn treatment that made all of the encapsulated drug
      available for chromatography. Multiple samples were assayed without any technical
      limitations. Second, the growth-inhibition antibacterial assay developed, which
      used the USP test organism Micrococcus Luteus and paper disks, was quantitative
      for both free and liposome-encapsulated ampicillin. Third, the physicochemical
      properties of encapsulated ampicillin include encapsulation efficiencies of 10 to
      50% for liposome concentrations in the range 10-200 mM (lipid), and a single rate
      constant to sufficiently and quantitatively describe the diffusion of
      encapsulated ampicillin, with half-lives in the range of 40 h. Fourth, the
      biological properties include the first direct evidence that encapsulated
      ampicillin retains full biological activity; that is, liposome-encapsulated
      ampicillin was active against extracellular bacterial colonies of Micrococcus
      luteus. Furthermore, encapsulation enhanced ampicillin stability. For example,
      free ampicillin in an aqueous solution that was stored for 5 weeks at 4 degrees C
      lost 50% of its initial activity, whereas liposome-encapsulated ampicillin (freed
      from unencapsulated drug) stored under the same conditions lost only 17% of its
      initial activity. The findings of this study, provide strong support for
      ampicillin-liposome formulations as valid dosage forms for this drug that are
      worthy of further experimental evaluations.

PMID- 9145394
TI  - Epibiotic microorganisms on copepods and other marine crustaceans.
AB  - Although the occurrence of microbial (algal, protozoan, bacterial, and fungal)
      epibionts on marine crustaceans and other invertebrates has been documented
      repeatedly, the ecological context and significance of these relationships
      generally are not well understood. Recently, several studies have examined the
      population and community ecology of algal and protozoan epibionts on freshwater
      crustaceans. Even so, the study of microbial epibionts in aquatic environments is
      still in its infancy. In this review, we summarize associations of microalgae,
      protozoans, and bacteria with marine crustaceans, especially copepods. We note
      differences and commonalities across epibiont taxa, consider host-epibiont
      cycling of nutrients, generate hypotheses relevant to the ecology of the host and
      the epibiont, and suggest future research opportunities.

PMID- 9145395
TI  - Advances in the study of marine viruses.
AB  - Free viruses are abundant in the world's oceans. With this realization has come
      renewed interest in marine viruses and the role viruses play in structuring
      marine planktonic communities, primarily members of the microbial assemblage. The
      principal means of studying marine viruses has been by electron microscopy. This
      review discusses the use of microscopy to study free viruses and compares the
      ultrastructure of free viruses with bacteriophages and viruses which have been
      cultured from marine hosts. Many of the free viruses are smaller than typical
      cultured bacteriophages, which suggests that either many native phages are
      smaller than cultured phages or that many of the free viruses may be members of
      those phage families with smaller size classes or, in some cases, that many free
      viruses may be eukaryotic viruses. Some of the forms currently considered free
      viruses may be "defective phage" or "phage ghosts," noninfectious particles
      produced by bacteria, or virus-sized inorganic/organic colloids and warrant
      further study. Gross virus ultrastructure cannot be used as the sole criterion
      for determining marine virus diversity, since, as with many microbes, many
      unrelated viruses have similar morphological characters. Determination of DNA or
      RNA content as well as studies of protein and DNA relatedness of marine viruses
      will be needed if we are to understand the complexity of marine virus
      assemblages. Another important direction for future work is the need for marine
      bacteriophage/host and virus/host systems in order to study the biology of virus
      infection.

PMID- 9145396
TI  - Evidence for the microbial basis of a chemoautotrophic invertebrate community at
      a whale fall on the deep seafloor: bone-colonizing bacteria and invertebrate
      endosymbionts.
AB  - To explore the microbial basis for a remarkable macrofaunal community at the site
      of a whale skeleton on the seafloor of the Santa Catalina Basin, we obtained
      samples of whale bone, bone-colonizing invertebrates, microbial mats, and the
      dominant fauna in the adjacent sulfide-rich sediments during Alvin expeditions in
      1988 and 1991. Invertebrate tissues were examined by transmission electron
      microscopy (TEM) and mats and bone-penetrating bacteria by epifluorescence
      microscopy (EM). Tissues from the dominant bivalve Vesicomya c.f. gigas, the
      mytilid mussel Idasola washingtonia, and selected gastropods and limpets were
      also assayed chemically for enzymes diagnostic of sulfur- and methane-based
      chemoautotrophy and for stable carbon isotopic composition. Results of all
      analyses were consistent with dominant sulfur-based endosymbioses in the clam and
      mussel (the first record of endosymbiosis in the genus Idasola) and the general
      absence of methane symbioses at the site, strengthening the analogy of the whale
      skeleton faunal community to those known from distant Pacific hydrothermal vent
      sites. Examples of minor endosymbionts, either nitrifying or methanotrophic cells
      according to internal membrane structures by TEM, raised the possibility of a
      supplemental mode of nutrition to the clam, or means to remove ammonia in the
      gill tissue, in the event of significant changes in the chemical environment.

PMID- 9145397
TI  - [Microanatomy and microsurgery for tumors involving the cavernous sinus].

PMID- 9145398
TI  - [Efficacy of MR angiographic original images on surgery for posterior
      communicating artery aneurysms].
AB  - This study evaluated the usefulness of axial source images of magnetic resonance
      angiography (MRA) on preoperative depiction of surgical topography around
      posterior communicating artery aneurysms. Twenty patients with posterior
      communicating artery aneurysms, two ruptured and eighteen unruptured, underwent
      conventional angiography as well as axial source and projection images obtained
      by three-dimensional time-of-flight MRA techniques. By comparing the topography
      based on these angiograms to that confirmed during surgery, we evaluated useful
      information specific to the source images of MRA. Source images of MRA visualized
      the posterior communicating artery and the anterior choroidal artery in eighteen
      cases (90%) and five cases (25%), respectively. The posterior communicating
      artery was recognized at a higher rate by source images of MRA than by
      conventional angiography (65%), while the anterior choroidal artery was
      recognized at a lower rate than by combined angiography (75%). We realized some
      specific information to the source images of MRA including the topographical
      relations between the aneurysmal neck and the orifice of the posterior
      communicating artery, the relations between the aneurysmal dome and the
      oculomotor nerve and the aneurysmal dome buried into the temporal lobe. The
      information suggested a satisfactory direction of safe aneurysmal clipping so as
      not to occlude the posterior communicating artery. It was concluded that the
      source images of MRA provided additional useful information on surgical
      topography in 60% of the cases involving posterior communicating artery
      aneurysms. Although not essential in every case, the information would be
      beneficial in cases with the aneurysmal dome suspected to be in the temporal lobe
      or when the surrounding topography can not be clearly understood by angiography.

PMID- 9145399
TI  - [Management and long-term follow-up results in patients with carotid artery
      dissection].
AB  - The recognized incidence of extra- and intracranial carotid artery dissection has
      increased concomitantly with the progress and development of diagnostic methods.
      However, management for this condition is still controversial. We report in the
      present study the management and long-term follow-up results of 15 patients with
      carotid artery dissection. Mean age of the patients at onset was 47.8 years old,
      and male/female ratio was 12:3. Two patients were considered to be traumatic
      dissections and the other 13 patients were spontaneous dissections. Dissection
      occurred in 10 patients at the extracranial carotid artery, in 4 at the
      intracranial carotid artery and in 1 at the middle cerebral artery. Nine of 15
      patients demonstrated hemiparesis and 5 complained of headache or facial pain.
      However, it was not possible to identify a characteristic symptom of dissection.
      Final diagnosis of dissection was made by cerebral angiography in all patients.
      Serial angiography was carried out in 10 of those, and 5 of the 10 patients
      showed some improvements of dissection in the cerebral angiogram. Treatment for
      those patients was selected according to the neurological and angiographical
      changes. Five patients were managed conservatively and 10 patients underwent
      surgical revascularization. During the follow-up period (mean 77.6 months), none
      of them showed any symptoms of reattack, and all but one, who died of heart
      failure 193 months after revascularization surgery, have lived independently.
      Although diagnosis of dissection was difficult because of the lack of
      characteristic symptom, serial angiography was a useful method for diagnosis and
      adequate management has led to a good clinical outcome.

PMID- 9145400
TI  - [Operative indication and risk factors for unruptured cerebral aneurysms].
AB  - Operative indication and risk factors for unruptured cerebral aneurysms were
      discussed. During the past 11 years, 38 aneurysms in 33 patients with a mean age
      of 54 years were operated on. All aneurysms were located in the anterior
      circulation; 16 were of carotid artery, 15 of the middle cerebral artery, 4 of
      the anterior communicating artery, and 3 of the distal anterior cerebral artery.
      Six cases (18.2%) developed neurological deficits postoperatively. The deficits
      were permanent in 3 cases (morbidity 9.1%). There was one operative death
      (mortality 3.0%). Operative risk factors were analyzed in 4 particular cases. Of
      these 4 cases, two cases had large aneurysms (14 and 16mm in diameter) located at
      carotid-ophthalmic and at the inferior wall of the carotid arteries,
      respectively. One developed unilateral blindness possibly due to operative
      manipulation, and the other showed hemiparesis with aphasia due to postoperative
      carotid stenosis caused by clipping. Of the rest 2 cases; one with multiple
      (carotid and middle cerebral) aneurysms developed hemiparesis because of
      postoperative stenosis of the atheromatous parent artery caused by clipping, and
      the other, with a large (17mm) aneurysm at the distal anterior cerebral artery,
      died of postoperative intracerebral hematoma. Both of these cases were associated
      with cerebral ischemic disease. All cases that developed postoperative
      neurological deficits had varying degrees of hypertension. Reviewing our series
      and other reports, it can be said that age is one of the most important factors
      that influence operative mortality. However, a lower risk of rupture develops as
      age increases. For those under 70 years of age, operation is considered safe in
      healthy individuals, especially among those without hypertension. However, in
      cases where there are large aneurysms, multiple lesions, less accessible
      locations and cerebral ischemic disease, operative risks should be kept in mind.
      Operative morbidity in these cases is relatively high compared to that found
      among others. Therefore, planning a meticulous surgical strategy and further
      careful operative manipulation are essentials, when surgical treatment is
      indicated.

PMID- 9145401
TI  - [Skull base aspergillosis granuloma originating from the sphenoid sinus: a case
      report].
AB  - A case of skull base Aspergillus granuloma originating from the sphenoid sinus
      was reported. This 64-year-old man complained of unilateral visual loss and
      serious facial pain, and was admitted to our department. He had been treated by
      transnasal sphenoidectomy because of sphenoid sinus aspergillosis. MRI showed a
      mass lesion located in the sphenoid sinus, cavernous sinus, ethmoid sinus and
      intraorbit. Angiography showed severe stenosis of the left internal carotid
      artery at the cavernous portion. As the symptoms gradually aggravated, we felt
      compelled to perform intracranial surgical treatment using the extradural
      approach to the skull base lesions. As the fibrous lesion was very hard and
      strongly adherent to the surrounding tissues, only partial removal of the lesion
      and resection of the trigeninal nerve were carried out. After surgery, the
      patient was released from severe facial pain and had an uneventful course. But,
      two months later, he died due to Aspergillus meningoencephalitis. Aspergillosis
      originating from the sphenoid sinus is rare, but it is known that some lesions
      show abrupt invasive extension to the skull base and the prognosis is bad. Early
      diagnosis and suitable treatment for the skull base or intracranial lesions is
      required.

PMID- 9145402
TI  - [Spontaneous intracranial hypotension with severe headache and typical
      neuroradiological findings: report of two cases].
AB  - Intracranial hypotension causes the postural headache that sometimes follows
      lumbar puncture. When postural headache and associated symptoms occur after
      lumbar puncture, the diagnosis is usually obvious. However, similar symptoms may
      occur after minor trauma or without an obvious precipitating cause (spontaneous
      intracranial hypotension: SIH). SIH is rare, but is now increasingly recognized
      as a cause of postural headache. We encountered two cases of SIH showing typical
      neuroradiological findings. Case 1 is a 47-year-old man who was admitted with
      severe frontalgia. CT scan revealed vague visualization of bilateral Sylvian
      fissures and slit ventricles. Spinal fluid pressure was 6cm H2O in the lateral
      recumbent position. Cerebrospinal fluid (CSF) showed slight lymphocytic
      pleocytosis. We treated him as having viral meningitis. His headache improved
      gradually and he was discharged 2 weeks later with slight occipitalgia. One week
      after discharge, he complained of severe headache again and plain CT showed
      bilateral subdural hematoma. The subdural hematoma in both sides was evacuated
      and his headache improved after the operation. Follow-up CT scans two months
      later showed normalization of ventricle size and cisterns. Case 2 is a 52-year
      old woman who was admitted with severe occipitalgia. CT scan on admission showed
      slit ventricles and the disappearance of the suprasellar cistern and the Sylvian
      fissure. Spinal fluid pressure was 3cm H2O. Gd-enhanced MRI showed remarkable
      meningeal enhancement and effacement of the optic chiasm suggesting brain
      sagging. Her headache improved 2 weeks later after strict bed rest and oral pain
      relief drugs. The follow-up MRI showed disappearance of abnormal meningeal
      enhancement and normalization of optic chiasma effacement. SIH is one of the
      important differential diagnoses of patients complaining of postural headache.
      Meningeal enhancement of gadolinium-enhanced MRI is an important finding to
      diagnose SIH. We have to consider SIH when diagnosing postural headache.

PMID- 9145403
TI  - [A case of cerebral arteriovenous malformation with accidental migration of a
      microcatheter during endovascular procedure].
AB  - This is a report of a case of cerebral arteriovenous malformation with accidental
      breakaway of a microcatheter during endovascular embolization. A 25-year-old
      female suddenly suffered severe headache. CT scan demonstrated intraventricular
      hemorrhage, and the angiogram revealed right parieto-occipital AVM. We performed
      endovascular embolization using a flow-directed microcatheter (1.5F BALT MAGIC
      catheter) 2 weeks after onset, and the microcatheter broke accidentally and a
      fragment of the soft tip migrated to the distal posterior cerebral artery during
      the procedure. Although we tried to retrieve the catheter using several retrieval
      devices, we failed. Two days after the procedure we undertook surgical treatment.
      The migrated catheter was recognized in a small feeding artery which was
      stretched tightly, so retrieval was very risky. Using hemoclips for trapping the
      part of the catheter which remained in the feeder, we were able to retrieve it by
      cutting the feeder. Flow-directed microcatheters are very usefull in endovascular
      procedures, but it is necessary to handle them carefully in accord with
      sufficient knowledge of their use and handling methods.

PMID- 9145404
TI  - [Two cases of delayed posttraumatic vasospasm followed by brain SPECT].
AB  - This is a report of two cases of delayed posttraumatic vasospasm. In case 1, a 68
      year-old male was injured by falling. He did not show any neurological deficits
      on admission. CT scan revealed a diffuse subarachnoid hemorrhage (SAH) without
      brain contusion. Aneurysm was not disclosed by angiography. On the 7th day after
      admission, he presented disorientation. Reviewed angiography revealed diffuse
      delayed vasospasm. 123I-IMP brain SPECT showed an extensive low perfusion area in
      the bilateral parietal portion. In case 2, a 71-year-old female experienced
      immediate development of a deep comatose state after head injury. CT scan on
      admission disclosed a massive acute left subdural hematoma and the severe
      compression of the left cerebral hemisphere by the hematoma. But traumatic SAH
      was not diffuse and was restricted to the left basal cistern. After emergency
      operation, her consciousness level improved and the mass effect of the subdural
      hematoma was diminished. On the 7th day after the operation, her neurological
      condition worsened. CT scan showed some infarction lesions in the left cerebral
      hemisphere and mild left cerebral swelling. Angiography on the same day revealed
      vasospasm in M2-M3 portion of left middle cerebral artery. HM-PAO brain SPECT
      disclosed low perfusion in the left parietal region, but a state of high
      perfusion in the other region. In case 1, vasospasm might have been derived from
      diffuse clots of traumatic SAH caused by the same process as postruptured
      aneurysmal vasospasm. In case 2, the region of vasospasm was not associated with
      traumatic SAH. It corresponded to the site of the brain contusion. It was
      suggested that the cause of vasospasm might have been the direct mechanical
      injury to the arterial wall and chemical substances deriving from the contused
      brain tissues. We conclude that SPECT or transcranial Doppler monitoring should
      be used for the early detection of posttraumatic vasospasm.

PMID- 9145405
TI  - [Fatal brain stem infarction due to rupture of a brain abscess: a case report].
AB  - We report a case of a brain abscess which initially presented with subcortical
      hematoma and ultimately resulted in fatal brain stem infarction due to its
      rupture into the subarachnoid space. A 50-year-old male was admitted to a nearby
      hospital with complaints of headache, fever, and sensory aphasia. He had
      ventricular septal defect found 15 years previously, sinusitis, and liver
      cirrhosis. Computerized tomographic (CT) scan revealed a left temporal
      subcortical hematoma. Gadolinium-DTPA enhanced magnetic resonance imaging (MRI)
      showed faint ring-like enhancement at the margin of the lesion. The left internal
      carotid angiogram demonstrated the vascular blush and early venous filling of the
      vein of Labbe. Administration of antibiotics and predonine resulted in resolution
      of fever within five days. MRI obtained 17 days after the onset showed typical
      ring-like enhancement. The mass was just adjacent to the lateral ventricle. The
      patient was transferred to our hospital for further examination and treatment 21
      days after the onset. Fever had recurred 2 days before admission to our hospital.
      One day after admission, the patient began to vomit. About 15 hours following
      this symptom, he suddenly became comatose and tetraplegic. CT scan demonstrated a
      rupture of the abscess. Emergent drainage from the lateral ventricle and the
      abscess cavity was undertaken. Follow-up CT scan revealed multiple infarctions
      involving the upper brain stem and the bilateral thalamus. He died on the 29th
      day after the onset. The mechanisms of hemorrhage with a brain abscess and
      cerebral infarction after rupture of brain abscess are discussed. Hemorrhage with
      brain abscess is extremely rare. However, brain abscess should be considered as a
      possible etiology of an atypical hematoma. To avoid fatal rupture of the brain
      abscess, immediate treatment is essential. Once the rupture of the brain abscess
      occurs, its contents might cause vasospasm severe enough to cause cerebral
      infarction.

PMID- 9145406
TI  - [Single stage excision for an intractable brain abscess and free rectus abdominis
      flap for reconstruction of the anterior skull base].
AB  - A case is presented of the frontal brain abscess following resection of squamous
      cell carcinoma of the maxillary sinus who had undergone reconstruction of the
      anterior skull base using a free rectus abdominis muscle flap. Local flap, ex.
      galeal flap, can be used for separating the cranial space from the paranasal
      sinuses and the nasopharynx, but it cannot provide reliable separation and
      protection of the brain from bacterial flora of the upper airway and it is too
      weak to support the brain in cases where orbital exenteration has been performed.
      The distant flaps such as the pectoralis major musculocutaneous flap, on the
      other hand, can provide a good alternative for reconstruction of the anterior
      skull base in such difficult cases, but frequently requires a secondary division
      of the pedicle. The free flap can circumvent such problems. We used the free
      rectus abdominis muscle flap and the postoperative course was uneventful. A bone
      graft was not necessary to reconstruct the anterior skull base.

PMID- 9145407
TI  - [Cerebral sinus thrombosis in a patient with protein S deficiency: a case
      report].
AB  - Cerebral sinus thrombosis associated with protein S deficiency is rare to the
      best of our knowledge. We report here a 22-year-old female who presented sudden
      onset of headache, vomiting and disturbance of consciousness. Neuroradiological
      studies including computed tomography scan, magnetic resonance imaging and
      cerebral angiography disclosed a huge cerebral sinus thrombosis in the territory
      of the superior sagittal sinus, torcular herophili, lateral sinus and straight
      sinus. Hematological studies confirmed the diagnosis of protein S deficiency. We
      summarize the reported cases of cerebral sinus thrombosis associated with protein
      S deficiency. For young patients presenting occlusive cerebrovascular disease, we
      stressed the importance of doing extensive hematological investigation to detect
      possible etiological factors, such as protein S deficiency, protein C deficiency,
      antithrombin III deficiency. Once we discover the etiology of a disease, we may
      be able to designate the precise treatment or regimen for each patient.

PMID- 9145408
TI  - [Orbital neurinoma presenting orbital apex syndrome].
AB  - A 75-year-old man presented a twelve-day history of double vision and retro
      ocular pain with rapid deterioration of visual acuity. Neurological examination
      on admission demonstrated right oculomotor palsy and abducence palsy, visual loss
      in the right eye, and hypesthesia and pain in the right supraorbital nerve. CT
      scan and MRI disclosed a mass in the right orbital apex. An emergency operation
      via a frontotemporal extradural approach was performed to decompress the optic
      nerve. The anterior clinoid process and minor wing of the sphenoid were drilled
      to expose the optic canal and superior orbital fissure. When the periorbita just
      beside the optic sheath was opened, a grayish colored mass was observed beneath
      the superior rectus muscle. The mass was dissected from the surrounding
      intraorbital tissue and was removed completely. The postoperative course was
      uneventful. The patient experienced complete disappearance of the ocular pain and
      complete restoration of his visual acuity. Orbital neurinoma is a benign tumor
      accounting for between 2.1 and 6.8% of all orbital tumors in the large series.
      The salient clinical symptom is exophthalmos followed by mass palpability.
      However, an orbital neurinoma presenting orbital apex syndrome is quite rare. In
      the case with orbital apex syndrome, it is sometimes impossible to recover visual
      acuity even though the optic nerve decompression is promptly performed. In such a
      case, only an emergency approach to the lesion can rescue the visual acuity.

PMID- 9145409
TI  - [A case of basilar impression treated with mandible splitting transoral
      approach].
AB  - We report a case of basilar impression treated with mandible splitting transoral
      approach surgery. A 39-year-old man presented a ten-year history of gait
      disturbance. He had experienced acceleration of his spastic paraparesis for the
      past few years. Neurological examination on admission demonstrated tetraparesis
      (MMT4/5), severe hyperreflexia in his arms and legs, severe sensory loss below
      C2, urinary retention and inability to open his mouth widely. Radiological
      findings showed the dens and the body of C2 are deeply invaginated to the atlas
      and the foramen magnum and medulla and upper cervical cord were markedly
      compressed by this basilar invagination. After carrying out posterior
      decompression and occipito-cervical fixation, we attempted to remove the
      invaginated dens and the C2 vertebral body using a conventional transoral
      approach. But limitation of mouth opening made operative fields narrow.
      Consequently because of insufficient anterior decompression his neurological
      deficits could not be alleviated. Employment of mandible splitting procedure
      brought about a wide operative view so that complete removal of the residual dens
      and 70% drilling out of the C2 body was made possible. Postoperative
      complications were negligible. Finally, great alleviation of his deficits was
      achieved. Mandible splitting procedure is effective for obtaining a wide
      operative field on the anterior approach to the craniocervical junction.

PMID- 9145410
TI  - Blindness and the coward's weapon.

PMID- 9145411
TI  - The cost-effectiveness of various modes of screening for primary open angle
      glaucoma.
AB  - Various modes of screening for glaucoma were defined in terms of different
      combinations of the three main tests (ophthalmoscopy (O), tonometry (T), and
      perimetry (P)), together with associated referral criteria. The number of
      referrals and true positives generated by each mode was estimated for a model
      population, which was distributed with respect to age, intraocular pressure
      (IOP), optic disc condition, visual field defects, family history of glaucoma,
      and myopic status, as indicated by epidemiological studies. The costs of primary
      examination, and also of the secondary examination of referrals, were estimated
      for each mode, thus enabling the total cost per true positive to be calculated
      (in Pound sterling at 1995 UK prices, subsequently converted to US dollars at
      Pound 1.00 = $1.55.) The modes using O and T routinely, with P either routinely
      or selectively on all glaucoma high-risk groups, were found to provide the best
      balance between sensitivity (> or = 80%) and cost per true positive. The latter
      was around $850 when the cost of ophthalmoscopy could be shared as part of a
      general eye examination. The calculations assumed a 0.6% prevalence of previously
      undetected glaucomas in the community: with higher prevalences, costs per true
      positive would be lower. Screening the 40-59 years age group was found to be
      about as economic as for older people, when life expectancy was taken into
      account. It was concluded that glaucoma screening of people over age 40 years
      could be justifiable, provided that it is worth more than about $850 to detect a
      new case. Whilst based on UK values, the analysis could be applied to different
      primary health care settings in other countries.

PMID- 9145412
TI  - Blindness and low vision in Jimma Zone, Ethopia: results of a population-based
      survey.
AB  - A population-based study on the prevalence of blindness and low vision was
      carried out in Jimma Zone, south-western Ethiopia between November 1994 and
      January 1995. A total of 7423 people from a sample of 8215 (90.4%) was examined.
      Sixty-three (0.85%) were blind (visual acuity less than 3/60 in the better eye)
      and 125 people (1.7%) had low vision (less than 6/18-3/60). Cataract and aphakia
      (52.4%), corneal opacity and phthisis bulbi (25.4%), and glaucoma (9.5%) were the
      major causes of blindness. Cataract (56.8%), refractive errors (28.8%), and
      corneal opacity (12.8%) were the major causes of low vision. Corneal opacity from
      trachoma was responsible for 20.6% of all blindness and 10.4% of low vision. The
      prevalence of visual impairment due to refractive errors was 5.1/1000 population.
      Almost 25% of the study population had active trachoma, and 0.9% of pre-school
      children had signs of vitamin A deficiency. Out of a total population of 2
      million an estimated 17,000 people are blind and 34,000 have low vision (i.e., a
      total of 51,000 people with visual impairment). Approximately 20,000 people
      require cataract surgery, 52,000 require lid surgery for trichiasis, 24,000
      require spectacles (excluding presbyopia), including 10,000 for significant
      refractive errors, half a million require treatment for active trachoma and 4,000
      require glaucoma treatment. Effective and feasible eye care programs need to be
      established in the zone and the available ophthalmic services have to be
      strengthened. These may be achievable through joint efforts of the community and
      the Ministry of Health in collaboration with non-governmental organizations. The
      available eye services are briefly described and recommendations made to meet the
      important needs for prevention of blindness in the region.

PMID- 9145413
TI  - Causes of blindness in northwest Cambodia.
AB  - A hospital-based study in the northwest of Cambodia identified 453 blind adults
      and 30 blind children seen consecutively at the provincial ophthalmic department
      between January and September 1994. Blindness was defined as a visual acuity of
      less than 3/60 in the better eye. Cataract was the cause of blindness in 266
      (59%) adults, of which 15 cases (3.3%) were surgical complications. Sixty-three
      cases (14%) were due to glaucoma and 53 (11.5%) patients had corneal scars, of
      which 12 (2.5%) were due to trachoma. Bilateral trauma, usually due to landmine
      injuries, accounted for 17 patients (4%). Of the 30 blind children, corneal
      scarring accounted for 12 cases (40%), congenital causes for 14 (47%) and optic
      atrophy secondary to meningitis for 4 (13%). There is at present an inadequate
      ophthalmological service for the vast majority of people living outside the
      capital Phnom Penh. These hospital-based data suggest that there is a need to
      train general doctors to surgically manage patients with visual loss from
      cataract and glaucoma, which together account for 70% of all cases of blindness,
      and highlight the need for a large population-based survey.

PMID- 9145414
TI  - Reliability of a food frequency questionnaire to assess dietary antioxidant
      intake.
AB  - OBJECTIVE: Epidemiologic evidence of a role for antioxidants in the prevention of
      chronic disease has been inconclusive, in part due to the difficulty of measuring
      past diets of free-living populations. The purpose of the current study was to
      examine the reliability of a 19-item, self-administered, semiquantitative, food
      frequency questionnaire to assess intake of the major dietary antioxidants.
      METHODS: Reliability was established by administering the food frequency
      questionnaire a second time by telephone. The subjects comprised 151 participants
      in the Melbourne Visual Impairment Project, a study of the distribution and
      determinants of eye disease in Melbourne residents aged 40 and over. RESULTS:
      Spearman correlation coefficients ranged from 0.39 for spinach to 0.76 for
      yoghurt, and all were highly significant (all p = 0.001). The reliability of the
      instrument was not influenced by gender, English speaking ability, or the number
      of days between the first and second administration of the questionnaire.
      CONCLUSION: In conclusion, we have shown this 19-item food frequency
      questionnaire to be highly reliable. It should be useful for anyone involved in
      the study of the relationship of dietary antioxidant intake to health outcomes in
      large populations where limitations of time and money prohibit the collection of
      more detailed dietary intake information.

PMID- 9145415
TI  - Viral resistance and CMV retinitis: design and methods of a prospective study.
      CRVR Research Groups. Cytomegalovirus Retinitis Viral Resistance Research Group.
AB  - A prospective study following a cohort of patients with newly diagnosed,
      previously untreated cytomegalovirus (CMV) retinitis is being conducted to study
      drug resistant CMV. Prior to initiation of treatment, patients undergo a baseline
      eye examination, fundus photography, and blood and urine culture for presence of
      CMV, and drug susceptibility testing against positive isolates. Patients are
      followed monthly with a detailed eye examination to diagnose progression of
      retinitis, and for fundus photography. Cultures are repeated at 1 and 3 months
      after enrollment, every 3 months thereafter, and at the time of treatment
      reinduction for the progression of retinitis. This study was designed to
      determine the prevalence and incidence of drug resistant CMV, as well as risk
      factors for the development of resistant CMV. It also will determine the
      correlation between clinical outcome, as measured both by eye examination and
      fundus photography, and viral resistance.

PMID- 9145416
TI  - The Wisconsin Age-related Macular Degeneration grading system: performance in an
      independent centre.
AB  - INTRODUCTION: Age-related Macular Degeneration (AMD) is the commonest cause of
      blindness in developed nations. Despite this, the epidemiology of AMD is poorly
      understood. A need for the documentation of AMD prevalence and incidence at a
      population level has stimulated the development of a comprehensive, observer
      based, photographic grading method for AMD in Wisconsin. AIM: To independently
      assess the performance of the Wisconsin method by self-taught graders outside its
      centre of inception. METHOD: The inter-observer variability and confidence limits
      for detection of change were assessed for two self-taught graders
      (ophthalmologists). Self teaching was achieved exclusively from documentation and
      photographs provided by the system developers in Wisconsin. 295 retinal
      photographs of elderly people were independently assessed for 13 features by each
      of the two graders. RESULTS: Weighted and unweighted kappa statistics, % exact
      and one step apart agreement, and confidence limits for detection of change were
      calculated for the graded features on a "by eye' basis, and where appropriate, on
      a "by retinal subfield' basis. Levels of agreement for weighted kappa were
      moderate to substantial for most features. 95% and 90% confidence limits for
      significant change beyond measurement error were determined in terms of scale
      increments. CONCLUSION: We conclude that the Wisconsin AMD grading system can be
      independently learnt from documentation and photographs alone, and that an
      acceptable level of performance is attainable by self-taught graders.

PMID- 9145417
TI  - Identification of casoxin C, an ileum-contracting peptide derived from bovine
      kappa-casein, as an agonist for C3a receptors.
AB  - Casoxin C (Tyr-Ile-Pro-Ile-Gln-Tyr-Val-Leu-Ser-Arg) is a bioactive peptide that
      was isolated from a tryptic digest of bovine kappa-casein as an anti-opioid
      peptide in longitudinal strips of guinea pig ileum. Casoxin C also evokes
      contraction of the ileal strips, and we found that this process was biphasic with
      rapid and slow components. The contractile profile was very similar to that of
      human complement C3a(70-77), which is the COOH-terminal octapeptide of C3a and
      has, although less potent, qualitatively the same biological activities as C3a.
      Casoxin C also has homology with C3a(70-77). The rapid contraction was mediated
      by histamine release and the slow contraction was mediated by a prostaglandin E2
      like substance, judging from the effects of various pharmacological inhibitors
      and antagonists on the ileal contraction. Casoxin C had affinity for C3a
      receptors (IC50 = 40 microM) in the radioreceptor assay. In addition, casoxin C
      showed phagocyte-stimulating activities. Casoxin C is therefore the first milk
      derived peptide identified, that acts through complement C3a receptors.

PMID- 9145418
TI  - MALDI-MS as a monitor of the purification and folding of synthetic eclosion
      hormone.
AB  - Analogues of the small protein Manduca sexta eclosion hormone (62 amino acids)
      were synthesized by Fmoc solid-phase methodology. Matrix-assisted laser
      desorption ionization mass spectrometry (MALDI-MS) was used to analyze the
      products of the syntheses and this information was used to design an efficient
      purification scheme. MALDI-MS was used to monitor the target products through
      purification and it was also used to monitor folding of the purified materials.
      The folded EH analogues were shown to be biologically active proteins with an in
      vivo bioassay using pharate adult moths, Heliothis virescens.

PMID- 9145419
TI  - A novel D-amino acid-containing peptide, fulyal, coexists with fulicin gene
      related peptides in Achatina atria.
AB  - Fulicin (Phe-D-Asn-Glu-Phe-Val-NH2) is a neuropeptide from ganglia of the African
      giant snail (Achatina fulica). Previously, the sequences of nine fulicin gene
      related peptides (FGRP-1 to -9) have been predicted from the cDNA encoding the
      ganglia fulicin precursor and the transcripts have been detectable in the heart.
      We synthesized twenty peptides related to fulicin and FGRPs containing either an
      L- or a D-amino acid at position 2 and used them to identify FGRPs in atrial
      extracts. We identified ten alpha-amidated peptides, including fulicin and
      confirmed their structures as follows: Tyr-Ala-Glu-Phe-Leu-NH2 (FGRP-9), [D
      Ala2]FGRP-9 (fulyal), [L-Asn2]fulicin, fulicin, Ser-Tyr-Asp-Phe-Val-NH2 (FGRP-2),
      Thr-Tyr-Asp-Phe-Leu-NH2 (FGRP-3), Tyr-Asp-Phe-Ile-NH2 (FGRP-5), Ser-Pro-Tyr-Asp
      Phe-Ile-NH2 (FGRP-6), Asn-Tyr-Asp-Phe-Val-NH2 (FGRP-7) and Ser-Pro-Tyr-Asp-Phe
      Val-NH2 (FGRP-8). We analyzed the biological activities of synthetic FGRPs using
      the snail penis retractor muscle. The results revealed that fulyal remarkably
      potentiated the tetanic contraction at concentrations as low as 10(-12) M. FGRP-9
      was about 10,000-fold less potent. Fulyal, like fulicin, seems to undergo
      preferential maturation to participate in the penis retractor muscle contraction
      as a neuropeptide containing a D-amino acid.

PMID- 9145420
TI  - Effects of cardioactive peptides on myocardial cAMP levels in the snail Helix
      aspersa.
AB  - Several cardioactive peptides from the pulmonate snail Helix aspersa were tested
      for their effects on myocardial cAMP levels, but only the family of small
      cardioactive peptides (SCPs) were clearly effective. SCP increased cAMP in a dose
      dependent manner; the time course was phasic. The structure-activity relations of
      this effect were examined with a set of 3 synthetic analogs having
      characteristics, at the carboxyterminal, of both the SCPs and FMRFamide-related
      peptides. The adenylate cyclase activator forskolin mimicked the mechanical
      effect of SCPs on the heartbeat. We conclude that the effect of SCPs on the Helix
      heart may be mediated by cAMP.

PMID- 9145421
TI  - Multiple bradykinin-related peptides from the skin of the frog, Rana temporaria.
AB  - The skin of the European common frog, Rana temporaria, contains a very high
      concentration of bradykinin (BK) but the mode of biosynthesis of the peptide is
      unknown. In addition to BK, we have isolated from an extract of R. temporaria
      skin the metabolites [des-Arg9]BK and [hydroxyprolyl3]BK. Peptides were also
      isolated that represent partially processed intermediates in the biosynthetic
      pathway to BK and comprise BK extended from its N-terminus by -Gly-Val-Ile-Pro
      Leu-Leu and three peptides comprising BK extended from its C-terminus by -Ile
      Ala, by -Ile-Ala-Pro-Ala-Ser-Thr-Leu, and by -Ile-Ala-Pro-Ala-Ser-Ile-Leu. The
      isolation of two C-terminally extended BK-containing peptides differing by a
      single amino substitution indicates that the biosynthetic precursor of frog skin
      BK may contain more than one copy of the BK sequence and/ or more than one gene
      encoding BK is expressed. The structures of the biosynthetic intermediates
      suggest that BK in frog skin is generated by the action of cellular
      endoproteinase(s) cleaving at the site of monobasic residues rather than by the
      action of the kallikrein-kinin system.

PMID- 9145422
TI  - Tachykinins and other biologically active peptides from the skin of the Costa
      Rican phyllomedusid frog Agalychnis callidryas.
AB  - Peptides present in a methanol extract prepared from skin of the Costa Rican frog
      Agalychnis callidryas of the Phyllomedusinae subfamily were studied by sequence
      analysis and pharmacological tests. Members of five different peptide families
      tachykinins, bradykinins, caerulein, opioid peptides and sauvagine-were found. In
      particular, the extract contained a number of tachykinins with the following
      sequences: Gly-Pro-Pro-Asp-Pro-Asn-Lys-Phe-Ile-Gly-Leu-Met-NH2, Gly-Pro-Pro-Asp
      Pro-Asp-Arg(Lys)-Phe-Tyr-Pro-Gly-Met-NH2, pGlu-Pro-Asp-Pro-Asp-Arg-Phe-Tyr-Pro
      Gly-Met-NH2, Gly-Pro-Pro-Asp-Pro-Asn-Lys-Phe-Tyr-Pro-Val-Met. The latter three
      peptides have the unusual C-terminal sequence Pro-Gly(or Val)-Met-NH2 rather than
      Gly-Leu-Met-NH2 found in many other members of the tachykinin family. The
      observed amino acid substitutions may be the reason for the marked decrease in
      the biological activity observed in all in vitro and in vivo tests, even through
      the spectrum of tachykinin activities was retained. A kassinin-like peptide, with
      the sequence Gly-Pro-Pro-Asp-Pro-Asn-Lys-Phe-Ile-Gly-Leu-Met-NH2, was also found
      in the A. callidryas skin. While kassinin has a much higher affinity for NK-3
      than for NK-1 receptors, the opposite is true for this A. callidryas peptide. The
      extract from A. callidryas skin also contained a new caerulein (pGlu-Asp
      Tyr(HSO3)-Lys-Gly-Trp-Met-Asp-Phe-NH2) and a phyllokinin (Arg-Pro-Hyp-Gly-Phe-Ser
      Pro-Phe-Arg-Ile-Tyr), as well as the opioid peptides dermorphin and
      [Hyp6]dermorphin, both previously isolated from different Phyllomedusa species.

PMID- 9145423
TI  - Use of antagonists to define tachykininergic control of intestinal motility in
      pigs.
AB  - The involvement of the tachykinins in extrinsic nervous control of motility was
      studied in isolated, vascularly perfused, porcine ileal segments. Substance P and
      neurokinin A (10(-8) M) stimulated motility, and nonpeptide NK1 and NK2 receptor
      antagonists (10(-6) M) abolished this. Electrical stimulation of the mixed
      extrinsic nerves (8 Hz) had no effect alone or with atropine (10(-6) M) or
      phentolamine (10(-5) M), but increased motility during coinfusion of both
      blockers. This effect was abolished by hexamethonium (3 x 10(-5) M), and was
      reduced by over 80% by the NK1 receptor antagonist. As previously shown,
      substance P and neurokinin A were released during nerve stimulation, only during
      blockade of alpha-adrenergic and muscarinic receptors, and the release was
      abolished by hexamethonium. Capsaicin infusions (10(-5) M) increased substance P
      and neurokinin A release, and weakly stimulated small intestinal motility, but
      this was not inhibited by the tachykinin antagonists. Our results suggest that
      intrinsic tachykinin-producing neurons, controlled by extrinsic, nicotinic,
      excitatory neural pathways, and extrinsic adrenergic, inhibitory pathways,
      participate in the regulation of small intestinal motility.

PMID- 9145424
TI  - alpha-MSH modulates experimental inflammatory bowel disease.
AB  - The mechanisms underlying inflammatory bowel disease (IBD) remain obscure but the
      importance of inflammatory processes is clear and most pharmacological therapies
      inhibit inflammation. The search for more effective agents with low toxicity
      continues. To test the possibility that the antiinflammatory/anticytokine peptide
      alpha-MSH can be used to control IBD, the peptide was administered to a murine
      colitis model. The peptide treatment had marked salutary effects: it reduced the
      appearance of fecal blood by over 80%, inhibited weight loss, and prevented
      disintegration of the general condition of the animals. Mice given alpha-MSH
      showed markedly lower production of TNF alpha by tissues of the lower colon
      stimulated with concanavalin A; the inhibitory effect of alpha-MSH on production
      of inflammatory nitric oxide by lower bowel tissue was even greater. The combined
      results indicate that alpha-MSH modulates experimental IBD, perhaps by inhibiting
      production within the gut of the local proinflammatory agents TNF alpha and
      nitric oxide, or by inhibiting inflammatory processes closely linked to these
      mediators.

PMID- 9145425
TI  - alpha-Melanocyte-stimulating hormone (alpha-MSH) and melanin-concentrating
      hormone (MCH) modify monoaminergic levels in the preoptic area of the rat.
AB  - The effect of perfusion of melanin-concentrating hormone (MCH) or alpha
      melanocyte-stimulating hormone (alpha-MSH) (100 ng/microliter) in the
      ventromedial nucleus (VMN) or medial preoptic area (MPOA) on monoaminergic levels
      of female rats was measured using microdialysis and HPLC-electrochemical
      detection. In the MPOA, alpha-MSH raised 5-HIAA concentration, whereas MCH
      reduced both 5-HT and 5-HIAA. Neither peptide had any effect in the VMN. The
      opposite effects of the peptides on the serotonergic system might be responsible
      for their antagonistic or opposite actions previously reported on several CNS
      functions. Dopamine may mediate the similar effects of the two peptides, because
      alpha-MSH inhibits dopaminergic release in the MPOA (but not VMN) and MCH tends
      to follow the same pattern.

PMID- 9145426
TI  - Melanin-concentrating hormone (MCH) antagonizes the effects of alpha-MSH and
      neuropeptide E-I on grooming and locomotor activities in the rat.
AB  - The intraventricular (i.c.v.) administration of the neuropeptide melanocyte
      stimulating hormone (alpha-MSH) is known to elicit a series of behaviors in the
      rat which include excessive grooming and other motor activities. In bony fish,
      the pigmentary effects of alpha-MSH can be antagonized by the neuropeptide
      melanin-concentrating hormone (MCH). We therefore examined whether MCH or its
      sister peptide neuro-peptide E-I (NEI), derived from the same precursor molecule,
      would modulate the effect of alpha-MSH on grooming and motor activity in the rat,
      or perhaps elicit some responses of their own. Rats were injected i.c.v. with
      either artificial cerebrospinal fluid, alpha-MSH, MCH, NEI, or with two peptides
      together, and behavioral responses were monitored over the next 65 min. The
      i.c.v. injection of 1 microgram MSH significantly enhanced grooming behavior. NEI
      at the same dose increased grooming, rearing, and locomotor activities. MCH alone
      had no behavioral effects but it annulled the behavioral responses induced by
      either alpha-MSH or NEI. alpha-MSH also antagonized the locomotor and rearing
      behavior induced by NEI. The physiological significance of these observations is
      discussed.

PMID- 9145427
TI  - [125I]Leu31, Pro34-PYY is a high affinity radioligand for rat PP1/Y4 and Y1
      receptors: evidence for heterogeneity in pancreatic polypeptide receptors.
AB  - Cloned receptors for the PP-fold peptides are subdivided into Y1, Y2, PP1/Y4, Y5
      and Y6. NPY and PYY have similar affinity for Y1, Y2, Y5 and Y6 receptors while
      PP has highest affinity for PP1. Pro34-substituted analogs of NPY and PYY have
      selectivity for Y1 and Y1-like receptors over Y2 receptors. In the present study,
      we found the putative Y1-selective radioligand, [125I]Leu31, Pro34-PYY, also
      binds with high affinity to the rat PP1 receptor in cell lines expressing the
      receptor. However, in rat brain sections, [125I]Leu31, Pro34-PYY does not appear
      to bind to the interpeduncular nucleus, a brain region containing a high density
      of [125I]-bPP binding sites. Therefore, it appears there is additional
      heterogeneity in receptors recognizing PP.

PMID- 9145428
TI  - The long-acting vasoactive intestinal polypeptide agonist RO 25-1553 is highly
      selective of the VIP2 receptor subclass.
AB  - RO 25-1553 is a synthetic VIP analogue that induced a long-lasting relaxation of
      tracheal and bronchial smooth muscles as well as a reduction of edema and
      eosinophilic mobilization during pulmonary anaphylaxis. In the present study, we
      tested in vitro the capacity of RO 25-1553 to occupy the different VIP/PACAP
      receptor subclasses and to stimulate adenylate cyclase activity. The cellular
      models tested expressed one single receptor subtype: Chinese hamster ovary (CHO)
      cells transfected with the rat recombinant PACAP I, rat VIP1, and human VIP2
      receptors; SUP T1 cells expressing the human VIP2 and HCT 15 and LoVo cells
      expressing the human VIP1 receptor. RO 25-1553 was threefold more potent than VIP
      on the human VIP2 receptor, 100- and 600-fold less potent than VIP on the rat and
      human VIP1 receptors, respectively, and 10-fold less potent than VIP and 3000
      fold less potent than PACAP on the PACAP I receptor. RO 25-1553 was a full
      agonist on the VIP2, the PACAP I, and the rat recombinant VIP1 receptor but a
      partial agonist only on the human VIP1 receptor. Thus, RO 25-1553 is a highly
      selective agonist ligand for the VIP2 receptor subclass.

PMID- 9145429
TI  - Cholecystokinin-induced antinociception is not blocked by CCK-A or CCK-B receptor
      antagonists.
AB  - To determine the relative importance of CCK-A, CCK-B, and opioid receptors in
      mediating the antinociceptive actions of cholecystokinin, we evaluated the
      actions of selective agonists and antagonists in the mouse hot plate assay. The
      agonists used were CCK (1-30 nmol i.c.v.), a CCK-A receptor agonist (SNF9019; 0.3
      10 nmol i.c.v.), and a CCK-B receptor agonist (SNF9007; 0.3-10 nmol i.c.v.). The
      antagonists used were the CCK-A receptor antagonist, L364,718 (12.5 nmol i.c.v.),
      CCK-B receptor antagonist, L365,260 (2.5-25 nmol i.c.v.), and the nonselective
      opioid receptor antagonist naloxone (1 mg/kg s.c.). CCK and its receptor
      selective analogues, SNF9019 and SNF9007, resulted in antinociception that was
      blocked by naloxone, but was not antagonized by L364,718 or L365,260. In
      contrast, in positive control experiments, the inhibitory effects of CCK,
      SNF9019, and SNF9007 on gastrointestinal propulsion in mice were antagonized by
      identical i.c.v. doses of L364,718 and L365,260. We conclude that centrally
      administered CCK produces antinociception in the mouse hot plate assay via opioid
      receptors, but independent of CCK-A or CCK-B receptors. It is necessary to
      speculate that other CCK receptors, not antagonized by currently available
      selective antagonists, may exist.

PMID- 9145430
TI  - Inhibition of human neutrophil functions by sulfated and nonsulfated
      cholecystokinin octapeptides.
AB  - The effects of CCK-8s and desulfated CCK-8 at concentrations ranging from 10(-14)
      to 10(-6) M were studied in vitro on several functions of human peripheral
      neutrophils: adherence to substrate, mobility (spontaneous and directed by a
      chemical gradient or chemotaxis), ingestion of inert particles (latex beads) or
      cells (Candida albicans), and production of superoxide anion measured by the
      nitroblue tetrazolium reduction test. The effect of CCK-8s on intracellular
      levels of cAMP was investigated as well as the implication of calcium in the
      action of CCK-8s on phagocytic function using stimulants and inhibitors of both
      intracellular and extracellular calcium channels. The two peptides, at
      concentrations from 10(-12) to 10(-8) M, inhibited significantly both mobility
      and ingestion capacities and increased adherence to substrate. A dose-response
      relationship was observed with a maximum inhibition of neutrophil functions at
      10(-10) M, CCK-8s and desulfated CCK-8 induced in these cells a significant, but
      transient, increase of cAMP levels at 60 s. Moreover, CCK-8s was found to inhibit
      completely the stimulation of latex bead phagocytosis in neutrophils produced by
      the calcium ionophore A23187. These results suggest that CCK-8 is a negative
      modulator of several neutrophil functions and that the inhibition of these
      activities could be carried out through an increase of the intracellular cAMP
      levels and a decrease of the extracellular calcium input.

PMID- 9145431
TI  - Synthesis and in vitro evaluation of new potent antagonists of growth hormone
      releasing hormone (GH-RH).
AB  - In the search for more potent antagonists of hGH-RH, 20 new analogs were
      synthesized, purified and tested in vitro. All the analogs were based on the N
      terminal sequence of 28 or 29 amino acid residues of hGH-RH, but contained D-Arg2
      and Nle27 modifications. Most analogs had Phe (pCl)6 and Agm29 substituents. The
      effect of other substitutions such as Abu8 and/or Abu15 and Ala15 and various
      hydrophobic and hydrophilic D or L amino acids at position 8 were also
      investigated. All the peptides were acylated at the N-terminus in an attempt to
      increase the antagonistic activity. In the superfused rat pituitary cell system,
      most analogs inhibited more powerfully the GH release induced by GH-RH than the
      standard antagonist [Ac-Tyr1, D-Arg2]hGH-RH (1-29)-NH2. Some antagonists were
      long acting. Among the peptides synthesized, antagonist PhAc[D-Arg2, Phe(pCl)6,
      Abu15, Nle27]hGH-RH (1-28) Agm (MZ-5-156) appeared to be the most potent and
      inhibited GH release in vitro 63-200 times more powerfully than the standard
      antagonist. MZ-5-156 and other antagonists showed high binding affinities to
      membrane receptors for GH-RH. Some of these hGH-RH antagonists could be further
      developed for possible onocological applications.

PMID- 9145432
TI  - Inhibition of GH release of rats by new potent antagonists of growth hormone
      releasing hormone (GH-RH).
AB  - Biological activity of a new series of potent GH-RH antagonists containing formyl
      or phenylacetyl group at the N-terminus of the sequence [D-Arg2,Phe(4
      Cl)6,Nle27]hGH-RH(1-29)NH2, as well as various substitutions in positions 8, 15,
      or 28, and in some cases Agm in position 29, was evaluated in vivo. All five
      antagonists, administered at a 27-fold molar excess to rats, suppressed the GH
      releasing effect of exogenous GH-RH(1-29)-NH2 by 64-75%. The inhibitory effects
      lasted for more than 15 min. The most potent analogue, PhAc-[D-Arg2,Phe(4
      Cl)6,Abu15,Nle27]hGH-RH(1-28)Agm (MZ-5-156), showed an in vivo potency 7-16 times
      higher than the early antagonist [Ac-Tyr1,D-Arg2]hGH-RH(1-29)-NH2, which was used
      as standard. MZ-5-156 was capable of decreasing serum GH levels after
      intravenous, intraperitoneal, or intramuscular administration. In vitro, in the
      superfused rat pituitary cell system, MZ-5-156 induced a prolonged inhibition of
      GH release after continuous long-term administration and showed a potency more
      than 100 times greater than the standard antagonist. These results show that N
      terminal acylation with phenylacetic acid of the sequence [D-Arg2,Phe(4
      Cl)6,Nle27]hGH-RH(1-29)-NH2, containing modifications in positions 8, 15, 28, or
      29, results in antagonists with high and protracted potency both in vivo and in
      vitro. In view of high antagonistic activity and prolonged duration of action,
      some of these antagonists of GH-RH may find clinical application for the
      treatment of IGF-dependent cancers.

PMID- 9145433
TI  - Production of bioactive salmon calcitonin from the nonendocrine cell lines COS-7
      and CHO.
AB  - To produce bioactive salmon calcitonin from the conventional nonendocrine cell
      lines, COS-7 and CHO, we devised a salmon calcitonin expression vector by
      combining the amino-terminus of human calcitonin precursor with a salmon
      calcitonin sequence, inserting the efficient furin-cleavable processing sequence
      Arg-X-Arg-X-Lys-Arg before salmon calcitonin, and deleting the carboxyl-terminal
      extension peptide. This chimeric calcitonin precursor terminates at glycine to
      easily receive an amidation reaction. COS-7 and CHO produced a high level of
      bioactive calcitonin by the resorption pit formation assay. Although amidating
      activity is highly expressed in CHO, but only a little in COS-7 cells, both cells
      produced a similar level of bioactive calcitonin. Thus, the engineered salmon
      calcitonin expression vector enables nonendocrine cells even with low amidation
      activity to produce bioactive calcitonin.

PMID- 9145434
TI  - Neuropeptide Y family of hormones: receptor subtypes and antagonists.
AB  - Neuropeptide Y (NPY) is the most abundant peptide present in the mammalian
      central and peripheral nervous system. NPY exhibits a variety of potent central
      and peripheral effects including those on feeding, memory, blood pressure,
      cardiac contractility and intestinal secretions. Classical pharmacological
      studies have shown that NPY effects are mediated by four different receptor
      subtypes, Y-1, Y-1-like, Y-2, and Y-3. However, the existence of numerous
      atypical activities provide strong evidence for the occurrence of additional NPY
      receptor subtypes. Pharmacological studies have further been facilitated by the
      recent cloning and expression of Y-1, Y-2, Y-4 (PP-1) and Y-5 receptors.
      Moreover, the cloned Y-5 receptor has been suggested to be the long awaited Y-1
      like receptor involved in feeding. Structure-activity studies have laid a good
      foundation towards the development of receptor selective compounds, and to date
      potent Y-1 selective peptide and nonpeptide antagonists have been developed. The
      need to clone numerous receptor subtypes and to develop receptor selective
      compounds for physiological and perhaps clinical use is expected to keep NPY
      research active for many years to come.

PMID- 9145435
TI  - Presence of adrenomedullin-like immunoreactivity in the human cerebrospinal
      fluid.
AB  - The presence of adrenomedullin-like immunoreactivity in the cerebrospinal fluid
      was studied by radioimmunoassay in 13 subjects with various neurological
      diseases. The concentrations of adrenomedullin-like immunoreactivity in the
      cerebrospinal fluid were 9.4 +/- 3.1 pmol/l (mean +/- SD, n = 13). Reverse-phase
      high performance liquid chromatography of the extract of the pooled cerebrospinal
      fluid showed that approximately 40% of the adrenomedullin-like immunoreactivity
      was chromatographically identical to human adrenomedullin (1-52). This is the
      first report that demonstrates the presence of adrenomedullin-like
      immunoreactivity in the human cerebrospinal fluid.

PMID- 9145436
TI  - Manipulation of colonic flora as ecosystem and metabolic organ: consequences for
      the organism. Proceedings of a workshop. Herdecke, Germany, June 1996.

PMID- 9145437
TI  - Human colonic microbiota: ecology, physiology and metabolic potential of
      intestinal bacteria.
AB  - In both health and disease, the colonic microbiota plays an important role in
      several areas of human physiology. This complex assemblage of microorganisms
      endows great metabolic potential on the large intestine, primarily through its
      degradative abilities. Many hundreds of different types of bacteria, varying
      widely in physiology and biochemistry, exist in a multitude of different
      microhabitats in the lumen of the large gut, the mucin layer and on mucosal
      surfaces. Both microbiota and host obtain clear benefits from association. For
      example, growth substrates from diet and body tissues, together with a relatively
      stable environment for bacteria to proliferate are provided by the host, which in
      turn has evolved to use butyrate, a bacterial fermentation product, as its
      principal source of energy for epithelial cells in the distal bowel. The main
      sources of carbon and energy for intestinal bacteria are complex carbohydrates
      (starches, non-starch polysaccharides). Carbohydrate metabolism is of great
      importance in the large intestine, since generically, and in terms of absolute
      numbers, the vast majority of culturable microorganisms are saccharolytic. The
      amounts and types of fermentation products formed by colonic bacteria depend on
      the relative amounts of each substrate available, their chemical structures and
      compositions, as well as the fermentation strategies (biochemical characteristics
      and catabolite regulatory mechanisms) of bacteria participating in
      depolymerization and fermentation of the substrates. Protein breakdown and
      dissimilatory amino acid metabolism result in the formation of a number of
      putatively toxic metabolites, including phenols, indoles and amines. Production
      of these substances is inhibited or repressed in many intestinal microorganisms
      by a fermentable source of carbohydrate. Owing to the anatomy and physiology of
      the colon, putrefactive processes become quantitatively more important in the
      distal bowel, where carbohydrate is more limiting.

PMID- 9145438
TI  - Metabolic effects of non-absorbable carbohydrates.
AB  - Food components which are incompletely absorbed in the small intestine or not
      absorbed at all but are delivered to the colon have been part of the diet
      throughout the course of human evolution. Our great ape cousins may derive 30% or
      more of their dietary calories from colonic uptake of short-chain fatty acids
      (SCFAs) generated in the colon. The metabolic effects of dietary carbohydrate
      entering the colon are many and include laxation, the growth of the fecal
      biomass, nitrogen entrapment and SCFA generation. These SCFAs in turn may nourish
      mucosal cells, spare glutamine utilization, enhance hepatic gluconeogenesis and
      lipogenesis and possibly influence renal handling of uric acid. The health
      implications are significant in terms of modifying risk factors for disease and
      disease prevention and justify interest in the metabolic effects of non
      absorbable sugars such as lactulose.

PMID- 9145439
TI  - Technical problems related to in vitro study of colon flora.
AB  - The complexity of colon flora and the technical problems encountered in the
      sampling techniques and their processing limit the study of its composition and
      activities. First, we list the main limitations related to the sampling procedure
      transport and storage. We show that (i) use of a cryoprotective medium is
      necessary for sample storage and (ii) that storage has to be at -40 degrees C.
      Second, bacterial analysis and enzymatic activities are examined. The lack of
      specificity of the culture media generally used means that systematic studies are
      difficult to carry out and that bacterial identification at species level
      requires genetic techniques. Third, we show that activities of procarcinogenic
      enzymes are significantly affected by any kind of storage. Finally, for
      statistics, the problem of the size and the nutritional habits of the studied
      population is examined.

PMID- 9145440
TI  - 16S ribosomal RNA-targeted oligonucleotide probes for monitoring of intestinal
      tract bacteria.
AB  - BACKGROUND: The composition of a sample of faecal bacteria can be determined by
      culturing different dilutions on specific media. However, not all bacteria can be
      cultured and media are not always specific. With a culture-independent approach a
      more accurate picture of the composition of the intestinal flora may be obtained.
      METHODS: Fluorescently labelled oligonucleotide probes targeted at 16S ribosomal
      RNA sequences specific for a bacterial genus were designed and applied for
      fluorescence in situ hybridization (FISH) of bacteria in human faecal samples.
      RESULTS: The mean number of Bifidobacterium spp. and the total number of
      anaerobic bacteria per gram of faeces were determined by culturing and with the
      probe technique. Although in both cases the number of Bifidobacterium spp. was
      about the same, 2.38 x 10(9) and 2.45 x 10(9), it was found that the contribution
      of Bifidobacterium spp. to the total composition is overestimated due to the
      lower number of total anaerobic bacteria estimated by culturing. CONCLUSION:
      Genus-specific or group-specific fluorescent 16S rRNA probes may become an
      invaluable tool in gut ecology studies.

PMID- 9145441
TI  - Metabolic consequences of total colectomy.
AB  - Colectomy is performed for inflammatory bowel disease, familial polyposis
      syndrome and colorectal carcinoma. Surgical procedures are ileostomy with or
      without pouch, ileorectal anastomosis or ileal pouch-anal anastomosis. One of the
      major functions of the intact large intestine is to absorb water and
      electrolytes. After colectomy, as much as 400-1000 ml of nearly isotonic
      ileostomy fluid may be excreted, resulting in a chronic salt and water depletion.
      This is compensated for by an activation of the renin-angiotensin-aldosterone
      system. Reduced urine volumes may cause kidney stones. Both dehydration and renal
      sodium retention are probably less frequent in patients with ileal pouch-anal
      anastomosis. Absorption of nutrients in general is not impaired by colectomy. The
      large intestine salvages energy from malabsorbed organic matter through
      absorption of the short-chain fatty acids produced in bacterial fermentation. In
      ileostomy patients, fermentation is negligible, which leads to a significant loss
      of energy in the ileostomy fluid. Pouches are colonized by a bacterial flora
      similar to colonic bacteria. In these patients conservation of energy from
      malabsorbed substrate may be similar to healthy subjects. Resection of ileum and
      bacterial colonization may lead to malabsorption of vitamin B12 and bile acids.
      The latter may cause increased incidence of biliary cholesterol stones. Pouchitis
      is a frequent problem which may be caused by a deficiency of short-chain fatty
      acids and glutamine in the pouch contents. It is concluded that although the
      colon is not essential as a digestive organ in man, colectomy results in a number
      of metabolic changes. The ileal pouch-anal anastomosis may in part substitute for
      the functions of the large intestine.

PMID- 9145442
TI  - Germ-free and conventional animal models for intestinal carbohydrate disposition.
AB  - Under conventional (CONV) conditions, the microbial flora is capable of breaking
      down most dietary derived carbohydrates as well as complex carbohydrates
      (glycolipids, glycoproteins, etc.) from the host. The major end products of these
      processes are short-chain fatty acids (SCFAs). In non-ruminants, most of the
      fermentation takes place in the large bowel. In ruminants, however, most acids
      are formed more proximal in the gastrointestinal (GI) tract. These microbial
      derived products may influence upon many host related functions, locally in the
      GI tract as well as elsewhere in the body. In germ-free (GF) animals, neglectable
      amounts of SCFAs are found in faeces. Parallel studies in GF and CONV animals
      given a standardized diet and ex-GF animals, receiving the same diet and
      mono/poly-associated with known microbial species, represent excellent models for
      answering such questions as (i) what can the microbes do? and (ii) what have the
      microbes done? These models allow detailed studies of the complex interplay
      between the host, his diet and his GI flora.

PMID- 9145443
TI  - Modification of the intestinal microflora using probiotics and prebiotics.
AB  - Probiotics and prebiotics modulate the composition of the human gut microbiota.
      The beneficial effects may result from suppression of harmful microorganisms or
      stimulation of organisms which contribute in a positive way to the nutrition and
      health of the host. Both types of supplement represent an attempt to reconstitute
      the gut flora to its normal composition which has been adversely affected by
      dietary and environmental stresses.

PMID- 9145444
TI  - Investigations of bifidobacterial ecology and oligosaccharide metabolism in a
      three-stage compound continuous culture system.
AB  - BACKGROUND: Several different types of in vitro fermentation systems are
      currently employed to investigate pro- and prebiotic activities in the human
      large intestinal microbiota, ranging from simple batch cultures, with or without
      stirring and pH control, to more complex models involving pH controlled single
      and multiple-component continuous culture systems. METHODS: In this
      investigation, we used a three-stage continuous culture model to study the
      activities of colonic bacteria. This fermentation system reproduces several of
      the nutritional and environmental characteristics of the proximal large intestine
      (vessel 1) and the distal colon (vessels 2 and 3), and was validated using
      bacteriological, metabolic and chemical measurements made with intestinal
      material obtained from different regions of the large bowel. In this paper, we
      report studies on prospective probiotic effects of Bifidobacterium longum NCFB
      2259 in relation to other bacterial populations, production of tyrosine and
      phenylalanine metabolites, and bacterial synthesis of enzymes involved in the
      formation of putatively genotoxic metabolites, including beta-glucosidase (GS),
      arylsulphatase (AS), beta-glucuronidase (GN), nitroreductase (NR) and
      azoreductase (AR). RESULTS: Bacterial activities at two different retention times
      were studied (31.1 and 68.4 h), which correspond to large intestinal transit
      times. At R = 31.4 h, significant probiotic effects were observed with respect to
      reductions in GS and GN, upon adding B. longum. However, despite the fact that
      this organism does not ferment aromatic amino acids or produce significant
      amounts of genotoxic enzymes, dysbiotic manifestations occurred in that both NR
      synthesis and dissimilatory tyrosine metabolism were stimulated. In contrast, at
      R = 68.4 h, GS formation increased between five and 20-fold, while GN and NR
      activities increased by a factor of two after adding the bifidobacterium. These
      data are reviewed in relation to potential health hazards that may be encountered
      with long-term probiotic administration. In the prebiotic experiments, the three
      stage fermentation system was operated at R = 65 h. Oligofructose was added to V1
      to give an initial concentration of 30 grams per litre, when the system was in
      steady state, to study its effects on a number of experimental parameters
      including bifidogenicity, bacterial growth, fermentation product formation and
      mutagenicity. After addition of the oligosaccharide, a multiplicity of effects
      were observed in V1, where synthesis of NR and AR, bifidobacterial populations
      and overall fermentation processes were stimulated, although these influences
      progressively diminished in V2 and V3. CONCLUSIONS: These studies indicate that
      bacterial metabolism and putative beneficial consequences associated with the
      breakdown of readily fermentable prebiotics in the large intestine may in some
      circumstances be spatially and temporally limited to the proximal bowel.

PMID- 9145445
TI  - Effects of lactulose and lactitol on colonic microflora and enzymatic activity.
AB  - The effects of lactulose and lactitol (2 x 10 g/d) were studied in 36 healthy
      volunteers in comparison to placebo. All parameters studied were affected by both
      treatments, lactulose in general leading to more pronounced changes compared to
      lactitol. Probiotic bacteria were increased, and putrefactive bacteria and
      potential pathogens were significantly reduced. These variations in colonic flora
      had the following consequences: (i) a reduced activity of pro-carcinogenic
      enzymes: azoreductase, 7 alpha-dehydroxylase, beta-glucuronidase, nitroreductase
      and urease activity; (ii) a global increase of short-chain fatty acids in faeces;
      (iii) an effect on pH and moisture of faeces, and (iv) also on aromatic compounds
      such as phenol, cresol, indole and skatol. The findings suggest that lactulose
      and lactitol are not comparable in their effect on the colonic microflora, its
      metabolism, and the consequent probiotic effects on human health. The differences
      found may also be of clinical relevance suggesting that neither compound is
      equipotent.

PMID- 9145446
TI  - Lactulose, lactic acid bacteria, intestinal microecology and mucosal protection.
AB  - During the fermentation of lactulose, short-chain fatty acids are formed with
      consequent lowering of the colon pH and modification of the microflora. Lactulose
      promotes the growth of lactic acid bacteria and bifidobacteria and, more
      specifically, Lactobacillus acidophilus in the colon. Lactulose and lactulose
      containing products fermented with lactic acid bacteria lower colonic pH
      balancing intestinal microecology and normalizing intestinal transit. In animal
      studies, lactulose promotes a mainly Gram-positive faecal microflora, but large
      doses of lactulose may be associated with transient diarrhoea. Our studies
      indicate that lactulose with lactic acid bacteria effectively relieves
      constipation in human volunteers. Lactulose with lactic acid bacteria in a
      fermented diary product can balance and prevent radiotherapy-associated diarrhoea
      and intestinal side effects. Normalizing the intestinal flora and stabilizing
      mucosal integrity with lactulose has beneficial effects in intestinal disorders.
      Lactulose and lactic acid bacteria offer a promising ingredient combination for
      future functional and special dietary foods in treating intestinal disturbances.

PMID- 9145447
TI  - In vitro and in vivo lactose and lactulose effects on colonic fermentation and
      portal-systemic encephalopathy parameters.
AB  - Lactose intolerance occurs in the majority of human groups, excluding people from
      Northern Europe. Because its effect is similar to that of lactulose, lactose
      seems to be an alternative treatment for patients with portal-systemic
      encephalopathy (PSE) and lactase deficiency. The mechanism of action of lactose
      is similar to that of lactulose. In vivo, lactose improves PSE parameters and
      causes acidic diarrhea. We performed in vitro studies in a fecal incubation
      system to investigate the biochemical and bacteriological effects induced by
      different substances customarily used for the treatment of patients with PSE
      (lactose, lactulose and Neomycin). In vitro experiments showed that lactose and
      lactulose decreased aerobic flora counts and reduced the pH of fecal incubation.
      Both disaccharides reduced the ammonia concentration in the incubation system.

PMID- 9145448
TI  - Effects of short-chain fatty acids on the inflamed colonic mucosa.
AB  - Selected inflammatory conditions of the distal alimentary tract may respond to
      topical SCFA treatment. The rationale for using SCFA enemas is based on
      Roediger's (1980) observation that butyrate is the preferred fuel of colonocytes
      and that SCFA deficiency could lead, in the short term, to mucosal hypoplasia
      and, in the long term, to colitis. The absence of luminal nutrients is especially
      evident in the excluded rectum after complete diversion of the faecal stream.
      Harig et al. (1989) were the first to treat successfully diversion colitis with
      SCFA irrigation (acetate 60 mM, propionate 30 mM, n-butyrate 40 mM). However,
      subsequent studies could not reproduce the initial positive data. In distal
      ulcerative colitis an impaired mucosal oxidation of SCFAs has been described
      despite their luminal abundance. Pilot studies using either the SCFA mixture or
      butyrate monotherapy have yielded promising results. However, extended
      confirmatory studies with a larger sample size have not yet been performed.
      Preliminary data are also available for the use of SCFA in pouchitis and
      radiation proctitis. In summary, SCFA topical therapy seems to be a promising
      option in distinct forms of inflammatory bowel disease; however, the routine use
      of SCFAs cannot be recommended until their efficacy has been confirmed in larger
      trials.

PMID- 9145449
TI  - Effects of short-chain fatty acids on gastrointestinal motility.
AB  - Besides their action on gut morphology and function, short-chain fatty acids
      (SCFAs), produced by bacterial fermentation of carbohydrates in the colon,
      influence gastrointestinal motility. As they are not present in the stomach and
      proximal small intestine, SCFAs do not directly affect motility of these
      segments. However, caecal infusion of SCFAs as well as colonic fermentation of
      lactulose induce a relaxation of the proximal stomach in humans, indicating that
      SCFAs can affect motility at a distance from their site of production. Moreover,
      this suggests that SCFAs may be involved in the so-called "ileocolonic brake',
      i.e. the inhibition of gastric emptying by nutrients reaching the ileo-colonic
      junction. In the terminal ileum, where their concentration may increase following
      a colo-ileal reflux, SCFAs stimulate contractions and shorten ileal emptying,
      which may protect ileal mucosa against the potentially harmful effects of the
      reflux of colonic contents. Although SCFAs are produced and concentrated in the
      colon, their action on motility of this organ is not clearly understood and may
      depend on concentration, molecular structure of the acids, responsiveness of the
      colonic segments and animal species. The mechanisms of action of SCFAs on
      gastrointestinal motility are not completely elucidated. They may involve
      systemic humoral and neural pathways as well as local reflexes and myogenic
      responses.

PMID- 9145450
TI  - Effect of lactulose on carbohydrate metabolism and diabetes mellitus.
AB  - BACKGROUND: Unabsorbable disaccharides, by reducing transit time and possibly
      glucose absorption, are expected to affect carbohydrate metabolism. AIM: To test
      the effects of a preparation containing fibre and lactulose in the form of
      biscuits on glucose and insulin levels in obesity. METHODS: In 10 obese patients
      glucose and insulin were measured in the fasting state and in response to a meal
      during two consecutive days on a strictly controlled diet; on one day a total of
      11 biscuits (10 g dietary fibre, 2 g raw fibre +8.2 g lactulose) were randomly
      substituted for an equicaloric part of a diet. RESULTS: Glucose and insulin in
      response to breakfast and to lunch were blunted by dietary fibre and lactulose,
      without any trend towards post-meal hypoglycaemia. Average day-time glucose
      decreased by 0.53 +/- SD 0.28 mmol/L, and insulin by 74.6 +/- 45.2 pmol/L. Plasma
      amino acids were higher during supplementation, ruling out malabsorption as a
      cause of glucose flattening. CONCLUSION: Because of the rationale of the
      preparation, good compliance of patients, and significant results in short-term
      experiments, the association of fibre and lactulose deserves more careful
      evaluation in long-term clinical studies.

PMID- 9145451
TI  - The metabolic importance of unabsorbed dietary lipids in the colon.
AB  - Digestion and absorption of lipids is a highly efficient process. From Western
      diets about 95% will be absorbed. This implies that together with lipids from
      endogenous sources 6-8 g of lipids will enter the colon daily. This input
      significantly increases during various lipid malabsorption syndromes. It has long
      been assumed that the biological fate of unabsorbed lipids is physiologically not
      relevant. However, significant microbial lipid metabolism occurs. Circumstantial
      evidence is arising which supports a role of unabsorbed lipid metabolites in the
      development of colonic diseases. Lipid metabolites may act as detergents in the
      colon, leading to mucosal injury and reactive hyperproliferation, which in its
      turn could promote tumour development. Lipid metabolites could also be
      transformed in biological active metabolites, which have a tumour promoting
      potency. More mechanistic information is needed on the colonic metabolic fate of
      lipids in order to develop strategies for manipulating colonic flora in the
      prevention of lipid related colonic diseases.

PMID- 9145452
TI  - Effect of lactulose and fiber-rich diets on bile in relation to gallstone
      disease: an update.
AB  - The primum movens in cholesterol gallstone formation is hepatic cholesterol
      hypersecretion and chronic supersaturation of bile. From this event a cascade of
      contributing factors can be differentiated: (i) Motility defects with impaired
      gallbladder contractility and gallbladder stasis, but also with small and large
      intestinal hypomotility. (ii) Multiple biochemical defects in gallbladder bile
      with increased biliary proteins, increased deoxycholic acid and rapid
      crystallization of biliary cholesterol from supersaturated unstable vesicles.
      There is considerable evidence that slow intestinal and colonic transit can
      increase the deoxycholic acid pool size and biliary cholesterol saturation.
      Changes in intestinal transit influence the anaerobic bacterial enzymatic
      biotransformation of conjugated cholate to more hydrophobic deoxycholate. This
      leads to biliary cholesterol hypersecretion and gallstone formation. Prokinetic
      drugs or administration of lactulose or fiber products like bran can change the
      slow intestinal transit favourably with subsequent reduction in deoxycholic acid
      formation and cholesterol saturation of bile. Whether these applications are
      indeed of value in the long-term prevention of gallstone disease, however, is
      doubtful, since fiber-rich diet in prevention of gallstone recurrence after
      complete gallstone dissolution was not successful.

PMID- 9145453
TI  - Chemoprevention of colorectal tumors: role of lactulose and of other agents.
AB  - Chemoprevention can be defined as an attempt at cancer control in which the
      occurrence of the disease is prevented by the administration of one (or more)
      chemical compounds. Main problems in chemoprevention studies are the choice of a
      suitable drug, the choice of an appropriate intermediate or definitive end point,
      and the definition of the population which should be investigated. Main classes
      of chemopreventive agents include vitamins, non-steroid antinflammatory drugs,
      minerals such as calcium or selenium, and other antioxidants such as N
      acetylcysteine. Chemoprevention is particularly appealing in colorectal cancer,
      either because these lesions develop through a multistep process, or owing to the
      concept of "field carcinogenesis'. Between 1985 and 1990 we carried out a
      controlled study in which antioxidant vitamins or lactulose were used in an
      attempt to prevent the recurrence of colorectal polyps after their endoscopic
      removal. Among the 209 patients who could be evaluated, polyps recurred in 5.7%
      of the individuals who were given vitamins (A, C and E), 14.7% of patients given
      lactulose and 35.9% of untreated controls (chi 2 = 17.1, P < 0.001). The study
      suggested that either antioxidant vitamins or lactulose could be effective in
      reducing the recurrence rate of adenomatous polyps. In a subsequent on-going
      study, lower doses of the same vitamins were tested versus N-acetylcysteine (600
      mg/day) or no treatment. Preliminary results showed a 40% reduction of the
      recurrence of polyps (versus controls) in individuals given N-acetylcysteine,
      while the effect of lower doses of vitamins was less appreciable. Definitive
      results of the study should be available by the end of 1998.

PMID- 9145454
TI  - Faecal steroids and colorectal carcinogenesis.
AB  - BACKGROUND: Colorectal cancer is a major disease of Western civilizations and
      diet may account for approximately 35% of cases. Epidemiologic studies reveal
      that the major dietary constituents implicated in the disease process are fat/red
      meat (causative) and fibre (protective). From this standpoint, toxicologists have
      evaluated a plethora of dietary and intestinal biochemical characteristics and
      steroids; the bile acids especially have received a great deal of attention.
      Formerly, bile acids and their bacterial metabolites were implicated, as either
      mutagens and/or carcinogens, but this was not proven. In recent times, based
      mainly on animal model systems, opinion favours that if bile acids and their
      metabolites have a role to play in colon carcinogenesis, they act at the
      promotion stages of the adenoma-carcinoma sequence-the secondary bile acids
      deoxycholic and lithocholic acids being of major importance here. From this
      standpoint, studies have been designed either to lower total bile acid
      concentration or at least to reduce dehydroxylation of the primary bile acids via
      high fibre dietary regimes. METHODS AND RESULTS: The prebiotics lactulose and
      lactitol (non-digestible dietary fibres) appear to have potential here, and so
      the effect of lactulose on fermentation by intestinal bacteria in a continuous
      culture model of the human colon was studied. Lactulose reduced dehydroxylation
      of chenodeoxycholic acid to the potentially toxic secondary bile acid lithocholic
      by over 90%. By contrast, lactitol, a reduced equivalent of lactulose, had little
      effect on 7 alpha-dehydroxylation of primary bile acids in the rectosigmoid colon
      of the miniature pig and in human faeces, but caused a significant decrease in
      steroid concentration, especially bile acids in human faeces. CONCLUSIONS: If
      secondary steroid metabolites have a role to play in colorectal carcinogenesis,
      then dietary supplementation with prebiotics may be ameliorative in high-risk
      groups.

PMID- 9145455
TI  - Effects of lactulose on nitrogen metabolism.
AB  - Lactulose is the most frequently utilized agent in the treatment of hepatic
      encephalopathy because of its efficacy and the fact that it has few serious side
      effects. How this non-absorbable disaccharide works has been a matter of
      controversy, but evidence suggests that metabolism by the enteric flora is
      necessary for its mechanism of action. When the intestinal flora metabolizes
      lactulose, bacterial incorporation of nitrogen increases, as does the bacterial
      mass. The presence of a carbohydrate and the acidic environment caused by the
      production of organic acids also act to reduce the breakdown of other nitrogen
      containing compounds to ammonia and other potential cerebral toxins. The
      administration of lactulose to humans causes an increase in fecal nitrogen, but
      very little increase in ammonia nitrogen. Most of the nitrogen is contained in
      the fecal bacterial and the soluble fractions of stool. The administration of
      lactulose causes a reduction in the urea production rate consistent with a
      reduced entry of ammonia into portal blood, but it does not appear to directly
      inhibit urea degradation. Other non-absorbable saccharides, particularly those
      contained in dietary fiber, appear to have effects similar to those of lactulose.
      There is some evidence that neomycin can be given with lactulose to cause an
      additive effect in the treatment of hepatic encephalopathy. This effect is most
      prominent in patients who have not responded adequately to lactulose alone. At
      this point, the other antibiotics studied do not appear to have additive effects
      with lactulose.

PMID- 9145456
TI  - A clinical hepatologist's predictions about non-absorbed carbohydrates for the
      early twenty-first century.
AB  - To put these predictions into perspective, the primary indication for lactulose
      therapy in the treatment of HE and SHE is presented and discussed. Six secondary
      indications for lactulose therapy are also listed and briefly commented upon. A
      dozen predictions about the status of lactulose are presented and briefly
      discussed. A. Lactulose will be the treatment of choice for HE.B. TIPS will be
      the most common cause of HE.C. Lactulose will not be approved in Mexico. D.
      Lactulose plus anti-diarrheal drugs will be agents for treatment of HE. E.
      Lactulose will not be the treatment of choice for constipation. F. Lactulose will
      not be used for Salmonella or Shigella carrier states. G. Lactulose will be
      routinely administered prophylactically after TIPS. H. Lactulose will be
      administered prophylactically to cirrhotic patients with portal hypertension. I.
      Lactulose plus anti-diarrheal drugs will be used for a variety of diverse
      purposes: (i) Suppression of bacterial growth; (ii) prevention of bacteriuria;
      (iii) diminution of cholesterol saturation of bile; (iv) adjunct treatment of
      gallstones with ursodeoxycholic acid; (v) Prevention of colon carcinoma.

PMID- 9145457
TI  - Perioperative anti-endotoxin strategies.
AB  - Lipopolysaccharides from the outer membrane of Gram-negative bacteria are potent
      stimuli for the production of numerous cytokines by the immune cells. The
      systemic inflammatory response to these gut-derived endotoxins is therefore
      dependent on the responsiveness of the immune system. This paper presents results
      on anti-endotoxin strategies and the responsiveness to endotoxin in animal models
      of liver failure. Following partial hepatectomy in the normal rat, anti-endotoxin
      treatment using the enteral endotoxin binder cholestyramine and the bactericidal
      permeability-increasing protein showed beneficial effects in terms of reducing
      the exaggerated metabolic and inflammatory responses. Similar beneficial effects
      of gut endotoxin restriction were found in bile duct ligated rats subjected to a
      laparotomy. The beneficial effects of anti-endotoxin strategies in these models
      were explained by completely different mechanisms. In partial hepatectomized rats
      the effects were explained by the direct inhibition of the stimulatory action of
      endotoxin on immune cells preventing an exaggerated inflammatory response. In
      contrast, in postoperative BDL rats the effects of anti-endotoxin therapy were
      explained by the restoration of endotoxin sensitivity of the immune cells
      resulting in an inflammatory response necessary for an adequate reaction to
      surgery. These different mechanism will be discussed in the light of the
      phenomenon of endotoxin tolerance.

PMID- 9145458
TI  - Overactivation of the immune system by translocated bacteria and bacterial
      products.
AB  - Gut-derived bacteria and their constituents, namely endotoxins, contribute to the
      pathogenesis of septic multi-organ failure. Ischemia, trauma, chronic
      inflammation, immunosuppression or reduced blood flow in the gut are conditions
      that enhance bacterial translocation, which in turn activates the non-specific
      immune system, i.e. macrophages and granulocytes to release mediators of
      inflammation such as cytokines, eicosanoids and degranulation products. Besides
      blood leukocytes, the liver macrophage population (Kupffer cells), the majority
      of macrophages in the organism, is a central part of the defense. When
      overactivated this system can turn against the host, resulting in inflammatory
      organ damage such as liver injury. A variety of cell and animal models was used
      to characterize the response of blood and liver leukocytes stimulated by bacteria
      and bacterial wall preparations. Inflammatory hepatocytotoxicity was studied in
      vivo as well as in a coculture model of Kupffer cells and hepatocytes. A
      combination of tumor necrosis factor-mediated apoptosis and interleukin-1
      mediated necrosis was identified as a crucial mechanism of endotoxin-inducible
      hepatocytotoxicity in vitro. Lactulose is believed to reduce bacterial
      translocation and could thus limit the adverse overactivation of the non-specific
      immune system. In addition, lactulose at high concentrations inhibited Kupffer
      cell release of inflammatory mediators and protected hepatocytes against
      macrophage toxicity. The clinical significance of this observation deserves
      further investigation.

PMID- 9145459
TI  - Lactulose and renal failure.
AB  - The introduction of lactulose as a new therapeutic agent for treatment of hepatic
      encephalopathy was a major breakthrough in this field. It was hypothesized that
      lactulose might prevent postoperative renal impairment after biliary surgery in
      patients with obstructive jaundice. The presumable mechanism purported was the
      diminished endotoxinemia by lactulose. Unfortunately, such a reno-protective
      effect has not been shown conclusively until now in clinical studies. In chronic
      renal failure lactulose is known to promote fecal excretion of water, sodium,
      potassium, amonium, urea, creatinine and protons. Thus, lactulose could be useful
      for the treatment of chronic renal failure. However, compliance to the therapy
      represents a major problem.

PMID- 9145460
TI  - Mycological aspects of gastrointestinal microflora.
AB  - There are two aspects about the presence of Candida in the human orointestinal
      tract: (i) it is a part of normal human flora and (ii) it is a risk factor for
      immunocompromised patients. The orointestinal tract can be considered a reservoir
      for Candida species, several of which are from the oral cavity, stomach, duodenal
      juice and faeces. Their germ counts in normal small and large bowel do not exceed
      10(4) cfu/ml resp.g. The input of Candida to a well-developed faecal flora system
      under continuous flow culture conditions did not lead to a multiplication of the
      yeast. The take in of faecal flora into a Candida continuous flow culture
      diminish Candida germ counts. If, however, the faecal flora was destroyed, e.g.
      by antibiotics, we found the yeasts multiplying, with the formation of germ tubes
      and mycelial structures. Colonization by Candida has to be seen as a starting
      point of the development of subsequent candidosis in immunosuppressed or
      intensive care patients. The best protection against Candida colonization in the
      gut is the existence of a normal bacterial flora. Lactulose, which promotes the
      Gram-positive potential of faecal flora, may protect indirectly by supporting the
      indigenous flora.

PMID- 9145461
TI  - Microflora-associated defense stimulating factors.
AB  - Mucosal surfaces are habitats for the physiological microflora and are closely
      related to the mucosal immune compartment (mucosa-associated lymphoid tissue,
      MALT). Recently, considerable evidence has accumulated showing that various
      members of the physiological microflora liberate low molecular weight substances
      which, apparently, are essential for the adequate immune response of the host.
      Antibiotic decontamination (e.g. of the BALB/c mouse gastrointestinal tract)
      results in a lack of generation of immunopriming microbial substances leading to
      immunosuppression. Biochemical analysis of the microbial substances revealed
      reproducible chromatographic fractions which selectively influence maturation,
      proliferation and activation of mononuclear immune cells.

PMID- 9145462
TI  - Protective effects of dietary lactulose and calcium phosphate against Salmonella
      infection.
AB  - BACKGROUND: Protection against intestinal infections by lactulose fermentation
      might be enhanced by calcium phosphate, due to the increased buffering capacity
      and/or inhibition of the cytotoxicity of luminal contents. METHODS: SPF rats were
      fed a low-calcium control diet, a low-calcium/lactulose diet or a high
      calcium/lactulose diet and orally infected with Salmonella enteritidis. Faeces
      and urine were sampled for microbiological and chemical analyses. RESULTS: The
      lactulose-fed rats had a better colonization resistance. Translocation was
      reduced by dietary calcium, whereas lactulose was ineffective. In addition,
      calcium supplementation stimulated lactulose fermentation, reversed the lactulose
      induced increase in cytotoxicity of faecal water and normalized growth and faecal
      consistency. CONCLUSIONS: The combination of dietary lactulose and calcium
      phosphate is protective against Salmonella infection.

PMID- 9145483
TI  - Fibrin sealant: scientific rationale, production methods, properties, and current
      clinical use.
AB  - Fibrin sealant is a complex plasma-derived product which is increasingly used as
      a biodegradable tissue adhesive or sealant to stop or control bleeding or provide
      air and fluid tightness in many surgical situations. This review describes the
      historical development of current fibrin sealant preparations and the scientific
      rationale behind the alleged physiological benefits of its major plasma-derived
      components. A comparison in the extraction methods and viral reduction treatments
      applied to current commercial products and autologous preparations, and their
      respective advantages and limits, are discussed. Application devices used for
      surgical applications are described. A survey of the major clinical applications
      in various surgical areas is presented. Current issues in terms of viral safety,
      definition of optimal fibrin sealant composition, and regulatory concerns,
      especially to demonstrate clinical efficacy, are also included.

PMID- 9145484
TI  - Evaluation of a new HTLV-I/II polymerase chain reaction.
AB  - AIM: Evaluation of a qualitative HTLV-I/II DNA polymerase chain reaction (PCR)
      test for the detection of HTLV-I/II DNA (Roche Diagnostic Systems, Branchburg,
      N.J., USA) in various panels. METHODS: The panels consisted of fresh EDTA blood
      samples from blood donors who were anti-HTLV-I/II ELISA repeatably reactive: 53
      were Western blot (WB) positive, 228 were WB indeterminate and 15 were WB
      negative. Elevent ELISA-negative blood donors were used as negative controls.
      Furthermore, specimens from 1 HTLV-II-infected intravenous drug user and from 1
      HTLV-II-infected blood donor were included in the panel. Peripheral blood
      lymphocytes were prepared by red blood cell lysis with the Roche washing solution
      and stored at < -23 degrees C until processing. Amplification products were
      analyzed with the HTLV-I/II detection kit. RESULTS: All 53 anti-HTLV-I/II ELISA-
      and WB-positive samples and both HTLV-II-positive samples tested positively by
      PCR. All 228 anti-HTLV-I/II ELISA-positive and WB-indeterminate, all 15 ELISA
      positive and WB-negative and all II ELISA-negative control samples tested
      negative by PCR. CONCLUSION: The Roche Amplicor HTLV-I/II test is a simple test,
      suitable for the confirmation of HTLV-I and-II infection in individuals with
      indeterminate or positive WB patterns.

PMID- 9145485
TI  - Identification of novel factor VIII inhibitor epitopes using synthetic peptide
      arrays.
AB  - OBJECTIVES: Mapping the antibody-binding sites on the factor VIII (FVIII) protein
      opens the prospect of studying the development of FVIII inhibitors and the
      alteration of inhibitor specificities over time. This paper describes a novel
      approach to the mapping of FVIII antibody-binding sites. METHODS: Immobilized
      synthetic peptide arrays covering 80% of the complete 2351 amino acid sequence of
      factor VIII (FVIII) were used to determine epitope specificity of 6
      alloantibodies and 3 autoantibodies inhibitory to FVIII activity. This detailed
      assessment was carried out using a modified enzyme-linked immunosorbent assay
      with plasma from normal persons or hemophilia A patients without inhibitors as
      negative controls. RESULTS: Antibody-combining sites could be differentiated in
      both a qualitative and quantitative manner and were patient-specific. Highly
      reactive peptides were restricted to specific sites in the A1-A3 and C1-C2
      domains and were not proximal to known proteolytic cleavage sites. Free peptides
      incubated in vitro with the plasmas of 3 patients significantly reduced residual
      inhibitor titers in a dose-dependent manner. CONCLUSION: This technique permits
      the study of the development and specificity of FVIII inhibitors, can detect and
      differentiate between inhibitory and noninhibitory antibodies using immobilized
      or free peptides respectively, permits correlation of antibody-combining sites
      with inhibition of FVIII activity and provides a basis for the development of
      inhibitor adsorption or neutralization technology.

PMID- 9145486
TI  - Computerized delivery control--a useful and safe complement to the type and
      screen compatibility testing.
AB  - OBJECTIVES: Faster and less labor-intensive crossmatching procedures are needed,
      but they must be as safe as the traditional antiglobulin method. We present
      twelve years' experience with a procedure involving antibody screening, blood
      group checks, and computerized delivery control (ABCD test). METHODS: We use a
      computer for validation and printing documents and declaring compatibility
      between patient and blood component, based on screening results and earlier
      recorded data about the patient. RESULTS: Of 257,400 units transfused during the
      period, 90% were declared compatible through the ABCD procedure, and 10% had to
      be crossmatched. We observed no hemolytic transfusion complications due to a
      failure of the procedure to detect red cell alloantibodies. Labor in the testing
      laboratory was reduced by 65% compared to a previous crossmatching period. Fewer
      blood units were returned unused. CONCLUSION: The procedure using a computerized
      system as a guard against human mistakes has been found to be safe and reliable
      and is now widely used in Sweden.

PMID- 9145487
TI  - Comparison between the conventional tube technique and the gel technique in
      direct antiglobulin tests.
AB  - OBJECTIVES: The direct antiglobulin test (DAT) is a diagnostic procedure
      demonstrating in-vivo antibody or complement coating on red cells. The gel
      technique (GT) for this test is sensitive and easier to do than the conventional
      tube technique (CTT). METHODS: We tested 52 newborns with hyperbilirubinemia and
      6 children and 17 adults with autoimmune hemolytic anemia (AIHA) using the (DAT)
      in the form of the conventional tube technique (CTT) and the gel technique (GT)
      simultaneously. The gradings of the agglutination reactions of both techniques
      were scored as 12, 10, 8, 5, 3, 0 for 4+, 3+, 2+, 1+ and w+ and negative,
      respectively. RESULTS: The GT yielded higher scores than the CTT (p < 0.01). The
      overall sensitivity and specificity of the GT were 93.5 and 88.6%, respectively.
      The specificity of the DAT-positive results in newborns was determined by IgG
      only, while in AIHA, it was determined by IgG and/or C3d and, in only one sample,
      by IgM. CONCLUSION: The GT is equal to or better than the CTT. Since the GT is
      simple, the exposure of blood bank personnel to the blood sample is low. We
      highly recommend the GT, especially in areas where HIV infection is prevalent.

PMID- 9145488
TI  - Flow-cytometric quantitation of anti-D antibodies.
AB  - OBJECTIVES: Quantitation of Rh antibodies is important clinically in predicting
      the risk of hemolytic disease of the newborn. We describe a flow cytometry method
      for the quantitation of anti-D antibodies that we developed in parallel to a
      recently described method. METHODS: As a secondary antibody we used whole IgG
      instead of Fab molecules. The advantages, besides lower cost, include a strong
      fluorescence signal with no need for amplification, and the possibility of
      diluting samples to minimize the risk of agglutination by IgM antibodies. We did
      extensive studies on reproducibility. RESULTS: Reproducibility was superior to
      the autoanalyzer method. The two methods were roughly in agreement in estimating
      low, medium, or high levels of anti-D with a correlation coefficient of 0.89. The
      autoanalyzer measures the in vitro agglutination of all anti-D antibodies whereas
      flow cytometry measures the amount of IgG anti-D bound to red cells, which is
      more like the in vivo situation. CONCLUSION: Further studies in a clinical
      setting will show whether flow-cytometric quantitation may improve the diagnostic
      value of anti-D concentration measurement.

PMID- 9145489
TI  - Sensitive determination of the RhD genotype in mixed samples using fluorescence
      based polymerase chain reaction.
AB  - OBJECTIVES: Prenatal determination of the fetal RhD status in pregnancies of Rh
      negative (Rh-neg) women by polymerase chain reaction (PCR) on DNA has become of
      increasing importance. Since determination of the RhD genotype in these cases is
      usually performed in samples containing both maternal Rh-neg and fetal Rh-neg or
      Rh-positive (Rh-pos) DNA, the sensitivity and specificity of PCR-based DNA
      detection are of crucial importance in the diagnosis of the fetal RhD status.
      METHODS: We developed a method for RhD typing using the PCR and a fluorescence
      based detection method that allows us to determine RhD-pos DNA even if it is
      mixed with large amounts of Rh-neg DNA. RESULTS: Using this approach, Rh-pos DNA
      could be detected in dilutions with Rh-neg DNA of as high as 1 in 10,000 (Rh
      pos/Rh-neg). Furthermore PCR amplification could also be carried out on DNA
      samples from persons with weak (Dweak) or partial (Dcat) RhD antigens.
      CONCLUSION: This method will be valuable in prenatal RhD typing after
      amniocentesis or after the isolation of fetal cells from maternal peripheral
      blood.

PMID- 9145490
TI  - Positive direct antiglobulin test due to antiphospholipid antibodies in normal
      healthy blood donors.
AB  - OBJECTIVES: Positive direct antiglobulin tests (DAT) occur occasionally, without
      obvious cause, among normal blood donors. This is sometimes associated with a
      false-positive serologic test for syphilis. Positive DATs due to antiphospholipid
      antibodies (APAbs) are well documented in the antiphospholipid syndrome with
      systemic lupus erythematosus and the primary antiphospholipid syndrome. METHODS:
      Using conventional haematologic and serologic methods, we tested 474,545 normal
      blood donors in the west of Scotland during the years 1991 through 1993. RESULTS:
      We identified 42 normal blood donors with a positive DAT and observed three who
      had positive DATs and false-positive VDRL tests, all of whom expressed raised
      APAbs. CONCLUSION: APAbs may be an incidental cause of positive DATs among
      healthy blood donors.

PMID- 9145491
TI  - Fine characterization of a series of new monoclonal antibodies directed against
      glycophorin A.
AB  - OBJECTIVES: Glycophorins A (GPA) and B (GPB) are the major sialoglycoproteins of
      the human erythrocyte (RBC) membrane. To prepare tools for the analysis of GPA
      and GPB, we produced a series of new monoclonal antibodies (mAbs) that identified
      epitopes of GPA. METHODS: Seven murine monoclonal antibodies directed to
      glycophorin A (GPA) were fully characterized by agglutination of untreated and
      enzyme-treated human erythrocytes, inhibition of agglutination using chemically
      modified glycophorins and peptides from GPA, immunoblotting, and binding to
      synthetic peptides on plastic pins. RESULTS: The antibodies identify epitopes
      located on four different portions of GPA. (1) NaM13-6D2 binds to the N-terminal
      portion of GPA and GPB carrying the N blood group antigen; (2) NaM26-3F4
      recognizes the homologous portion of GPA and GPB corresponding to their amino
      acids 6-26; (3) NaM10-2H12, NaM16-IB10 and NaM10-6G4 are specific for the amino
      acid sequence 38-45 of GPA; and (4) NaM37-5F4 and NaM13-4E4 bind to the amino
      acid residues 119-124 located on the intracellular ponion of GPA. CONCLUSION:
      These antibodies represent precise tools to investigate GPA and related molecules
      in different cells and tissues.

PMID- 9145492
TI  - Simultaneous genotyping of human platelet antigens by hot start sequence-specific
      polymerase chain reaction with DNA polymerase AmpliTaq Gold.
AB  - OBJECTIVES: Human platelet alloantigen (HPA) typing has potential clinical
      relevance in a variety of contexts. We can improve methods for HPA genotyping by
      complementing our knowledge of the DNA sequence polymorphisms of HPA genes and
      experience with various DNA-based HPA typing techniques. METHODS: A newly
      available DNA polymerase, AmpliTaq Gold (Perkin Elmer), provided in an inactive
      state and activated by heat, makes it possible to perform a hot start polymerase
      chain reaction (PCR) in order to prevent nonspecific amplification during the
      setup of PCR. To establish a practical procedure for HPA-1, 2, 3 and 5
      genotyping, we applied the AmpliTaq Gold for a hot start PCR and employed 8 pairs
      of published sequence-specific primers (SSP). A simple simultaneous genotyping of
      these 4 HPA systems could be rapidly achieved with high specificity. RESULTS: The
      HPA gene frequencies observed in 126 randomly selected German blood donors were
      0.82 and 0.18 for HPA-1a and 1b, 0.92 and 0.08 for HPA-2a and 2b, 0.63 and 0.37
      for HPA-3a and 3b and 0.90 and 0.10 for HPA-5a and Sb, respectively. CONCLUSION:
      Using our hot start PCR-SSP procedure with AmpliTaq Gold a simple, rapid and
      reproducible genotyping for HPA-1, 2, 3 and S systems could be achieved.

PMID- 9145493
TI  - Family characteristics as mediators of the influence of problem drinking and
      multiple risk status on child mental health.
AB  - Structural equation modeling was used to test a theoretical model in which family
      cohesion and family reframing coping were hypothesized as mediators between
      family drinking problems, multiple risk factors, negative life events, and child
      mental health (conduct disorder, depression, anxiety) in two-parent families.
      Family cohesion mediated the relationships of family drinking problems and
      negative life events to child conduct disorder and depression. Negative life
      events mediated the relationships of family drinking problems and family multiple
      risk to child conduct disorder. Family reframing coping did not function as a
      mediator nor was it related to child mental health when other factors were
      considered simultaneously. Results indicate that increasing family cohesion and
      reducing sources of stress within the family (negative life events) represent
      promising areas of interventions for children with problem-drinking parents.

PMID- 9145494
TI  - Mobilizing positive reinforcement in communities to reduce youth access to
      tobacco.
AB  - A community intervention to mobilize positive reinforcement for not selling
      tobacco to young people was evaluated. The intervention had five components: (a)
      mobilization of community support, (b) merchant education, (c) changing
      consequences to clerks for selling or not selling to those under 18, (d)
      publicity about clerks' refusals to sell, and (e) feedback to store owners or
      managers about the extent of their sales to adolescents. A multiple baseline
      design experiment was conducted, in which two small Oregon communities received
      the intervention, while two other continued in baseline. Outlets' willingness to
      sell was assessed repeatedly by teenage volunteers. The intervention
      significantly reduced the proportion of stores willing to sell. Mobilizing social
      and material reinforcement for stores not selling tobacco to young people is a
      viable means of reducing such sales. It may be especially valuable in communities
      where laws against sales to minors go unenforced.

PMID- 9145495
TI  - Effectiveness of a consultation intervention to promote tobacco control policies
      in Northwest Indian tribes: integrating experimental evaluation and service
      delivery.
AB  - A quasi-experimental replication of an intervention for promoting tobacco control
      policies in Northwest Indian tribes is described and the process of intervention
      including issues of collaboration among research institutions and Indian
      organizations is discussed. The policy intervention was evaluated using a pretest
      posttest design wherein 20 tribes that had served as wait-list controls now
      received the intervention. The intervention comprised a tribal representative
      attending a kickoff orientation; follow-up visits to the tribes; distribution of
      tobacco policy workbooks; and phone call consultations. Policy status and
      stringency were assessed by means of telephone interviews with two key contacts
      per tribe, and by a count of enacted policies. There were significant pre-post
      changes in the primary outcome measure, a composite summary score of tobacco
      policy stringency, and changes were also reflected in enacted policies. The
      intervention effects observed were similar to those found in the prior randomized
      trial and suggest a robust, disseminable intervention. Much of the success
      achieved was attributed to the role of an Indian organization in planning the
      project and implementing the intervention and evaluation protocols.

PMID- 9145496
TI  - Choreography of the squid's "nuptial dance".
AB  - A mass spawning of squid resembles, at first glance, a chaotic "nuptial dance"
      (1). But for the first time, we have applied 3-D, radio-linked acoustic
      positioning (RAP) to this confusing process, and our early results now reveal a
      choreography that is, in fact, well organized in time and space. Remote tracking
      with RAP of individual Loligo vulgaris reynaudii off South Africa has provided
      insights into the daily sequence of behaviours that lead these animals to
      aggregate for sexual selection. Each dawn, the squid navigate for several
      kilometers, towards the shore, to small, well-defined zones near egg beds on the
      substrate. After several hours of circling above the egg beds, a pelagic, 3-D lek
      like aggregation of large males forms: females are drawn in, and the aggregation
      condenses as the females and males pair, mate, and lay eggs. Smaller "sneaker
      males" remain on the periphery of the mating arena and, from this station,
      attempt extra-pair copulations (EPCs). The mating system of squids is thus
      unexpectedly complex, rivaling those of mammals and birds (2, 3). Commercial
      squid-jigging fishermen in South Africa have recently been attracted to the
      spawning grounds, and they have been successful. Moreover, their activities may
      be selective for large males. Thus, attention should be devoted to ensuring that
      such targeted fishing does not alter the characteristics of squid population
      genetics. Remote tracking and video observations, in combination with genetic
      analyses, may offer a new opportunity to monitor mating effort and reproductive
      success, and thus to manage the fishery.

PMID- 9145497
TI  - Bacterial endosymbionts in the gills of the deep-sea wood-boring bivalves
      Xylophaga atlantica and Xylophaga washingtona.
AB  - Bacterial endosymbionts found in gill tissues in several bivalve families convert
      otherwise unavailable energy sources (sulfide, methane, or cellulose) to forms
      readily metabolized by their hosts. We investigated the existence of such a
      symbiosis in two species of Xylophaga (family Pholadidae). The genus Xylophaga
      includes opportunistic species that are the predominant colonizers of wood at
      depths greater than 150 m. It has been hypothesized that, like their shallow
      water counterparts the shipworms (family Teredinidae), species of Xylophaga
      utilize wood for nutrition. Results from transmission and scanning electron
      microscopy of X. atlantica and X. washingtona clearly demonstrate the presence of
      endosymbionts that resemble the shipworm endosymbionts both morphologically and
      in their anatomical location within the gills. Xylophaga and the teredinids both
      have a caecum packed with wood chips but lack the dense populations of
      microorganisms associated with cellulose digestion in termites or ruminants.
      These observations suggest that Xylophaga has evolved a symbiotic solution to
      wood digestion similar to that seen in shipworms. Hence, the Xylophaga symbiosis
      suggests a mechanism for the conversion of terrestrially derived cellulosic
      carbon from wood into animal biomass in the deep sea.

PMID- 9145498
TI  - Characterization of the cytotoxic activity of nitric oxide generating N-nitroso
      compounds.
AB  - The NO-generating abilities of aromatic N-nitroso compounds (nitrosoureas,
      nitrosamides and nitrosamines), and N-acetyl-S-nitroso-DL-penicillamine at
      ambient temperature were compared by employing the Griess reaction. 3,3-Dibenzyl
      1-(4-tolyl)-1-nitrosourea showed the greatest NO-generating ability among the
      tested compounds. The NO-generating ability of the aromatic N-nitrosoureas and N
      nitrosamides was greater than that of the N-nitrosamines, presumably reflecting
      differences in electrostatic repulsion between the carbonyl oxygen and nitroso
      oxygen in these compounds. In addition, a conjugative effect between the aromatic
      ring carbon and neighboring nitrogen influences the NO-generating ability; the
      conjugative effect in the case of N-nitrosoureas and N-nitrosamides having an
      ortho-alkyl substituted aromatic ring, or N-nitrosamines having a bulky N-group,
      such as tert-butyl, is decreased by an increase in steric hindrance around the
      nitroso group. The N-NO bond then becomes more stable. The NO-generating ability
      was related to the reciprocal of the ID50 value for growth inhibition of cultured
      L-5178 Y cells by the aromatic N-nitroso compounds. On the other hand, NO
      production from the aliphatic N-nitroso compounds was not observed under our
      conditions, and these N-nitroso compounds did not show effective cytotoxic
      activity.

PMID- 9145499
TI  - Studies on cardiac ingredients of plants. XIII: Chemical modification of gitoxin
      to cardiotonic compounds without vascular effect.
AB  - Nitrated gitoxins (4) and bufotoxin homologues with various lengths of alkyl
      chain at C-3 of the steroid nucleus (10) were prepared from gitoxin (1). The
      pharmacological activities of the resulting compounds (4 and 10) were evaluated
      by measurement of inhibitory effect on NA+, K(+)-adenosine triphosphatase
      (ATPase) prepared from dog kidney, positive inotropic effect (PIE) on isolated
      guinea-pig papillary muscle preparations, and the effect on smooth muscle using
      the mesenteric artery from spontaneously hypertensive rats. Most of the compounds
      showed a smaller contractile effect on the arterial muscle. Among these
      compounds, gitoxin 3"-nitrate (4g) exhibited the most desirable biological
      activities, such as PIE comparable to that of 1, 1.25 times wider concentration
      dependent range than 1, and lack of contractile activity on vascular muscle.

PMID- 9145500
TI  - Acacia concinna saponins. I. Structures of prosapogenols, concinnosides A-F,
      isolated from the alkaline hydrolysate of the highly polar saponin fraction.
AB  - A highly polar saponin mixture from pods of Acacia concinna (Leguminosae) was
      hydrolyzed with alkali to yield five new triterpenoidal prosapogenols named
      concinnosides A (6), B (3), C (7), D (4), and E (8), together with four known
      glycosides, acaciaside, (2), julibroside A1 (10) julibroside A3 (9),
      albiziasaponin C (5), and their aglycone, acacic acid lactone (1). The structures
      of these new prosapogenols were elucidated based on spectroscopic means. A less
      polar saponin fraction from the pods gave spinasteryl glucoside and its dihydro
      derivative.

PMID- 9145501
TI  - Synthesis and pharmacological evaluation in mice of new non-classical
      antinociceptive agents, 5-(4-arylpiperazin-1-yl)-4-benzyl-1,2-oxazin-6-ones.
AB  - Several 5-(4-arylpiperazin-1-yl)-4-benzyl-1,2-oxazin-6-ones have been synthesized
      and tested for analgesic activity in a visceral pain model (phenylbenzoquinone
      induced writhing test = PBQ test). A good correlation has been found between the
      antinociceptive effects of drugs and both their lipophilic and steric properties.
      The most active derivatives 5c and 5f, with intraperitoneal ED50 values of 10.5
      and 10.3 mg kg-1 respectively, were more extensively investigated by evaluating
      their analgesic activity in a somatosensory pain model (hot plate test), as well
      as their sedative properties. Furthermore, naloxone suppressed the effect of 5c
      and 5f in the PBQ test, though these derivatives were ineffective to potentiate
      morphine analgesia. Pretreatment with yohimbine did not significantly attenuate
      the analgesic effects of 5c and 5f. In addition, pretreatment with 5
      hydroxytryptophan associated with carbidopa also failed to potentiate the
      antinociceptive effects of 5c and 5f. So, a part of the analgesic activity of 5c
      and 5f seems to be related to an opioidergic mechanisms, especially at the mu
      receptor level. Molecular modeling studies performed on the opiate drug morphine
      and on the most stable conformer of 5f showed structural similarities between
      these two molecules.

PMID- 9145502
TI  - 2-Arylmethyl-1,4-benzoquinones. II. Novel inhibitors of platelet aggregation:
      synthesis and pharmacological evaluation.
AB  - Two new series of 2-arylmethyl-1,4-benzoquinones (2 and 3) were synthesized for
      evaluation of their pharmacological activities. These compounds showed
      significant inhibition of platelet aggregation and some of them possessed a
      protective against endothelial cell injury. Structure-activity relationship
      studies indicated that 2b, 2d and 3b are potent inhibitors of platelet
      aggregation induced by arachidonic acid (AA) with an IC50 in the range of 1-10
      micrograms/ml. Among them, 3b showed a significant inhibitory activity against
      endothelial cell injury caused by hydrogen peroxide (H2O2) at 1 microM.

PMID- 9145503
TI  - Inhibitory effects of quassinoid derivatives on Epstein-Barr virus early antigen
      activation.
AB  - Short-term in vitro assays for tumor promoters and antitumor promoters (Epstein
      Barr virus activation test) were carried out for semisynthetic quassinoids (3-7),
      which were obtained by esterification of the C-15 OH group of deacetylated
      isobrucein-B (2). All the ester derivatives showed higher antitumor promoting
      activity than that of the potent compound 2. A compound containing a fluorinated
      aliphatic ester showed the highest potency.

PMID- 9145504
TI  - Synthesis and hypolipidemic activity of diesters of arylnaphthalene lignan and
      their heteroaromatic analogs.
AB  - A series of diesters of arylnaphthalene lignan and their heteroaromatic analogs
      were synthesized and evaluated for hypolipidemic activity. The disasters with
      modifications at C-3 showed excellent hypocholesterolemic and high-density
      lipoprotein (HDL) cholesterol-elevating activities. Structure-activity analysis
      indicated that the 2-pyridylmethyl ester 5l has the optimum activity.

PMID- 9145506
TI  - Studies on the constituents of Broussonetia species. II. Six new pyrrolidine
      alkaloids, broussonetine A, B, E, F and broussonetinine A and B, as inhibitors of
      glycosidases from Broussonetia kazinoki Sieb.
AB  - Six new pyrrolidine alkaloids called broussonetine A, B, E, F, and
      broussonetinine A and B were isolated from the branches of Broussonetia kazinoki
      Sieb. (Moraceae). Broussonetine A, B, E and F were formulated as 2 beta
      hydroxymethyl-3 beta-hydroxy-5-alpha- (10-oxo-13-hydroxytridecyl)-pyrrolidine-4-O
      beta-D-glucopyranoside (1), 2 beta-hydroxymethyl-3 beta-hydroxy-5 alpha-(9-oxo-13
      hydroxytridecyl)-pyrrolidine-4-O-beta-D-glucopy ran oside (2), 2 beta
      hydroxymethyl-3 alpha,4 beta-dihydroxy-5 alpha-(1,13-dihydroxy-10-oxo-tridecyl)
      pyrrolidine (3), and 2 beta-hydroxymethyl-3 alpha,4 beta-dihydroxy-5 alpha-(1,13
      dihydroxy-9-oxo-tridecyl)-pyrrolidine (4), respectively. Broussonetinine A and B
      (5 and 6) were also isolated and identified as the aglycones of 1 and 2. 3 and 4
      exhibited a strong inhibition of alpha-glucosidase, beta-glucosidase, beta
      galactosidase and beta-mannosidase, while 5 and 6 showed a strong inhibition of
      beta-galactosidase and alpha-mannosidase.

PMID- 9145505
TI  - Synthesis and nematocidal activity of aralkyl- and aralkenylamides related to
      piperamide on second-stage larvae of Toxocara canis.
AB  - Seventy-nine aralkyl- and aralkenylamides related to piperamides were synthesized
      and their nematocidal activity against second-stage larvae of dog roundworm,
      Toxocara canis, was examined. The activity was greatly dependent on the alkyl
      chain length and the nature of the amine moiety, but was scarcely affected by the
      presence or absence of double bond(s) in the chain. The alkyl chain lengths which
      showed the strongest activity in a series of homologues were m = 11 for the
      pyrrolidine amides and m = 13 for the N-methylpiperazine amides. Although
      piperamides (3,4-methylenedioxyphenyl homologues) showed the strongest activity
      among the homologues tested, methoxy substituent(s) on the aromatic ring did not
      have much effect on the activity. However, conversion of the methoxy group to a
      hydroxy group greatly decreased the activity and shortened the chain length
      giving the strongest activity. Calculated log P values of non-phenolic aryl
      piperamides fell in the range from 3.5 to 4.5, whereas those of hydroxyphenyl
      piperamides were smaller, suggesting that different mechanisms are involved in
      the nematocidal activity of phenolic and non-phenolic compounds.

PMID- 9145507
TI  - Preparation of novel (1-->3)-beta-D-glucans having reducing glucose side chains.
AB  - Novel (1-->3)-beta-D-glucans (GPBCD, GPECD, GP6CD, and GP3CD) having reducing
      glucose side chains were prepared from a linear (1-->3)-beta-D-glucan (curdlan:
      CD) with halogeno glucose isopropylidene derivatives in dimethyl sulfoxide
      containing dimsyl sodium, followed by treatment with 40% trifluoroacetic acid to
      remove protecting isopropylidene groups. The side chain glucose moiety was linked
      or directly or through a spacer at various positions except for its anomeric
      carbon.

PMID- 9145508
TI  - Synthesis and biological evaluation of monoindolyl and indolocarbazolyl
      oxazolones and imidazolones.
AB  - Eight compounds structurally related to protein kinase C inhibitor MDL 27032 and
      substituted with indole moieties were synthesized. Their activities towards
      protein kinase C (PKC) and protein kinase A (PKA) were determined. Their effect
      on PKC-mediated contraction of rat tracheal smooth muscle, their
      antiproliferative activity on two murine tumor cell lines, melanoma B16 and
      leukemia P388 and their antimicrobial activity on a gram-positive bacterium
      Bacillus cereus were also examined. The mammalian and bacterial cell
      antiproliferative activity, as well as vasorelaxant effect, observed for some of
      them could not be correlated to PKC or PKA inhibition. Only bulky bis-indolyl
      compounds exhibited biological activity in these experiments. Rigid
      indolocarbazoles had the strongest antiproliferative activity.

PMID- 9145509
TI  - Determination of organophosphorous pesticides in biological samples of acute
      poisoning by HPLC with diode-array detector.
AB  - We have developed a simple and rapid method for measuring 11 organophosphorous
      pesticides (dichlorvos, methidathion, salithion, malathion, fenitrothion,
      fenthion, parathion, diazinon, ethylthiometon, O-ethyl O-(4
      nitrophenyl)phenylphosphonothioate (EPN) and chlorpyrifos) and one metabolite (3
      methyl-4-nitrophenol) of fenitrothion in serum and urine of acute poisoning
      patients by HPLC with a diode-array detector. An aliquot of the biological sample
      after deproteinization by acetonitrile was injected into C18 column using
      acetonitrile-water as a mobile phase. The detection limits in serum and urine
      ranged from 0.05 to 6.8 micrograms/ml at a wavelength of 230 nm. This method was
      successfully applied to two actual cases of acute poisoning.

PMID- 9145510
TI  - Validity of the 13-C-urea breath test for the diagnosis of Helicobacter pylori
      infection.
AB  - Infection with Helicobacter pylori (H. pylori) plays an important role in the
      pathogenesis of gastritis, peptic ulcer and gastric cancer, and the 13C-urea
      breath test (13C-UBT) is a convenient and non-invasive method for the detection
      of H. pylori in the stomach. We have examined the sensitivity, specificity and
      accuracy of 13C-UBT. The 13CO2/12CO2 ratio was measured using infrared
      spectroscopy (IR) and gas chromatography/mass spectrometry (GC-MS).

PMID- 9145511
TI  - Molecular biology of the pore-forming cytolysins from Staphylococcus aureus,
      alpha- and gamma-hemolysins and leukocidin.
AB  - Staphylococcus aureus is an important opportunistic pathogen. It produces a
      variety of extracellular proteins, which may play important roles in infections
      by this bacterium. Staphylococcal alpha-toxin is a pore-forming 33-kDa
      polypeptide. In the first part of this article, we will refer to the roles of
      cell membranes in the pore formation by alpha-toxin as well as the molecular
      dissection of alpha-toxin for understanding its pore-forming nature.
      Staphylococcal gamma-hemolysin and leukocidin are bi-component cytolysins, which
      have different cell specificities towards erythrocytes and leukocytes,
      respectively. We have found that these bi-component cytolysins share a common
      component. In the second part of this article, we will refer to the current
      status of knowledge of molecular cloning of the genes coding for gamma-hemolysin
      and leukocidin, molecular domains of the toxins which decide the cell
      specificities, and mode of action of these bi-component toxins.

PMID- 9145512
TI  - Cytotoxicity of cholestane 3 beta,5 alpha,6 beta-triol on cultured intestinal
      epithelial crypt cells (IEC-6).
AB  - The effects of cholestane 3 beta,5 alpha,6 beta-triol on intestinal epithelial
      crypt cells were investigated using the IEC-6 cell line. Cholestane 3 beta,5
      alpha,6 beta-triol decreased SH groups (glutathione and protein SH) in the cell,
      and showed cytotoxicity in a time-dependent manner. Although the concentration of
      cholestane 3 beta,5 alpha,6 beta-triol used in this study (100 microM) was very
      high compared with that in plasma of experimental animals, cholestane 3 beta,5
      alpha,6 beta-triol did not show any cytotoxicity on IEC-6 cells without fetal
      calf serum (FCS). The level of cytotoxicity was dependent upon the concentration
      of FCS in the culture medium. Unknown components in FSC (not VLDL or LDL) were
      suggested to be associated with the cytotoxicity of cholestane 3 beta,5 alpha,6
      beta-triol. Moreover, the fact that even heat-treated FCS (100 degrees C for 30
      min) still mediated the cytotoxicity suggested the participation of non-protein
      components.

PMID- 9145513
TI  - The phylogeny of species of the genus Issatchenkia Kudriavzev
      (Saccharomycetaceae) based on the partial sequences of 18S and 26S ribosomal
      RNAs.
AB  - The ten strains of Issatchenkia species were examined for their partial base
      sequences of 18S and 26S rRNAs. In the 18S rRNA partial base sequences (positions
      1451-1618, 168 bases), the strains of the species of the genus Issatchenkia were
      found to be not uniform phylogenetically. The calculated base differences
      numbered 5-0. The strains of Issatchenkia species examined had 3-1 base
      differences with the type strain of Pichia membranaefaciens. Especially, the type
      strain of Issatchenkia orientalis, the type species of the genus Issatchenkia was
      found to be closely related phylogenetically to that of P. membranaefaciens. The
      calculated number of base differences was only one. The base sequences on the
      fingerprint segment were comprised of four bases (four kinds of AUAU, CCAU, AUAG,
      and ACAU), as found in P. membranaefaciens (ACAA). In the 26S rRNA partial base
      sequences, the calculated number of base differences was 8-0 (positions 1611
      1835, 225 bases), and the calculated percent similarities were 61-80 (positions
      493-622, 130 bases), within the genus Issatchenkia. Discussion was made
      phylogenetically and taxonomically, especially on the phylogenetic relationship
      between the type species of the genera Issatchenkia and Pichia and on a
      circumscription of the genus Issatchenkia.

PMID- 9145514
TI  - Hydrolysis of xylan by Aspergillus niger immobilized on non-woven fabrics.
AB  - Aspergillus niger, which produces xylan-degrading enzymes, was immobilized on non
      woven fabrics. The maximum xylan hydrolysis activity (15 U/cm3-support) and the
      highest stability were obtained when the fungus was immobilized on non-woven
      fabric made of silk. The enzymatic properties of the immobilized preparation were
      similar to those of the free enzyme. Ten times repeated batch hydrolysis of birch
      wood xylan was done over a period of 450 h. Hydrolysis of different xylan
      substrates such as oat spelts and rice bran by the immobilized mycelia was also
      investigated.

PMID- 9145515
TI  - Chemical and functional properties of mutastein, an inhibitor of insoluble glucan
      synthesis by Streptococcus sobrinus.
AB  - Mutastein, a potent inhibitor of insoluble glucan synthesis by Streptococcus
      sobrinus, is a protein with a molecular weight of approximately 2 x 10(6). Amino
      acid and ELISA analyses suggested that mutastein is a mixture of heterogenous
      polymers of alpha-casein contained in the culture medium of the producing strain,
      Aspergillus terreus M3328. Mutastein strongly inhibited the primer-dependent
      insoluble glucan synthase of S. sobrinus B13. The primer-independent soluble
      glucan synthase was not affected by mutastein while primer-dependent soluble
      glucan synthase was slightly activated.

PMID- 9145516
TI  - Purification, characterization, and cDNA cloning of a novel alpha-galactosidase
      from Mortierella vinacea.
AB  - A novel alpha-galactosidase, designated alpha-galactosidase II, was isolated from
      the culture filtrate of Mortierella vinacea. The molecular size of the purified
      enzyme estimated by gel filtration was 60 kDa, which agreed with that, 51-62 kDa,
      estimated by SDS-PAGE. The enzyme was thermolabile at neutral pH, but the
      addition of BSA to the enzyme solution at the concentration of 0.01% increased
      its stability considerably. The enzyme appears to be novel because it showed a
      distinct substrate specificity from other microbial alpha-galactosidases on
      galactomanno-oligosaccharides, prepared from galactomannan, that is, the enzyme
      liberated not only side-chain alpha-galactosyl residue from 6(3)-mono-alpha-D
      galactopyranosyl-beta-1,4-D-mannotetraose but also terminal alpha-galactosyl
      residue from 6(3)-mono-alpha-D-galactopyranosyl-beta-1,4-D-mannotriose. In
      addition, the enzyme acted on galactomannans effectively. alpha-Galactosidase II
      cDNA was cloned and its nucleotides sequenced. The deduced amino acid sequence
      showed that the mature enzyme consisted of 376 amino acid residues with a
      molecular mass of 41,334 Da. The derived amino acid sequence of the enzyme showed
      31-49% sequence similarity with those of alpha-galactosidases from other origins.

PMID- 9145518
TI  - Optimization of the culture medium for growth and the kinetics of lactate
      fermentation by Pediococcus sp. ISK-1.
AB  - The growth of a newly isolated strain of Pediococcus sp., designated ISK-1, was
      very slow and the concentration of cells in the medium remained low. Fermentation
      with an initial 30 g/liter glucose required about 60 h. To stimulate
      fermentation, we attempted to optimize the medium by flask culture and jar
      fermentation tests. Mevalonic acid and mieki (soy bean hydrolyzate) stimulated
      fermentation and increased the rate of formation of DL-lactate. Kinetic analysis
      of the fermentation showed that mevalonic acid markedly increased the specific
      glucose consumption rate and the specific lactate production rate. Mieki and
      mevalonic acid had a synergistic effect, but the effect of mevalonic acid was
      different from that of mieki.

PMID- 9145517
TI  - Purification and properties of beta-fructofuranosidase from Clostridium
      perfringens.
AB  - beta-Fructofuranosidase [EC 3.2.1.26] in Clostridium perfringens was induced in
      the presence of sucrose and suppressed in the presence of glucose or maltose. The
      enzyme seems to be present in protoplasm in a soluble state. The beta
      fructofuranosidase from C. perfringens cells grown on sucrose was purified by
      ammonium sulfate precipitation. DEAE-cellulose chromatography, Sephadex G-150 gel
      filtration, and hydroxylapatite chromatography to a homogeneous state. The
      molecular weight was 37,000 by gel filtration using Sephadex G-150 and by SDS
      polyacrylamide gel electrophoresis. The amino acid composition is not much
      different from those of other microorganisms, but the Glx content was a little
      higher. The enzyme was inhibited by heavy metals, such as Hg2+, Cu2+, and Ag+, as
      well as pCMB; the activity was restored by incubating with mercaptoethanol.
      Fructose and amines including Tris and aniline had inhibitory effects.

PMID- 9145519
TI  - Microbial extracellular glycolipid induction of differentiation and inhibition of
      the protein kinase C activity of human promyelocytic leukemia cell line HL60.
AB  - The biological activities of 7 microbial extracellular glycolipids including
      mannosylerythritol lipid (MEL)-A, MEL-B, polyol lipid (PL), rhamnolipid (RL),
      sophorose lipid (SL), succinoyl trehalose lipid (STL)-1, and STL-3 were
      investigated. All glycolipids except for RL were found to induce cell
      differentiation instead of cell proliferation in the human promyelocytic leukemia
      cell line HL60. To identify the differentiation direction of the induced cells,
      the leukocyte esterase activities were cytologically investigated, and the
      results showed that MEL-A, MEL-B, and PL induced HL60 to differentiate into
      granulocytes, while SL, STL-1, and STL-3 induced differentiation into monocytes.
      The 6 effective glycolipids also increased nitroblue tetrazolium (NBT) reducing
      ability, which is a common differentiation-associated characteristic in monocytes
      and granulocytes. Furthermore, it was also observed that these 6 glycolipids
      inhibited the activity of phospholipid- and Ca(2+)-dependent protein kinase.
      Additionally, the 6 effective glycolipids also induced the human myelogenous
      leukemia cell line K562 and the human basophilic leukemia cell line KU812 to
      differentiate into monocytes, granulocytes, and megakaryocytes.

PMID- 9145520
TI  - Purification and some properties of endo-1,4-beta-D-xylanase from a fresh-water
      mollusc, Pomacea insularus (de Ordigny).
AB  - Endo-1,4-beta-D-xylanase (EC 3.2.1.8) was purified from viscera of a fresh-water
      mollusc, Pomacea insularus (de Ordigny). The purified enzyme, with a molecular
      weight of 47,000, gave a single protein band in sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). The amino-terminal sequence was
      Ala-Ala-Gly-Ala-Gly-Val-Thr-Ser-Glu-Lys-Asp-Arg-Leu-Arg-Arg-Ser-Asp-Lys -Thr-Val
      His-Val-Asn-. The enzyme was stable from pH about 4.5 to 9.5 and had its maximum
      activity at pH about 5.5. The purified enzyme produced X2, X3, X4, and larger
      xylooligosaccharides from birchwood xylan. The enzyme activity was greatly
      inhibited by Ag+, Hg2+, Cu2+, N-bromosuccinimide, and p-chloromercuribenzoic
      acid. On the other hand, the enzyme activity was greatly elevated by the addition
      of chloride ion.

PMID- 9145521
TI  - Non-radioactive adenosine 5'-phosphosulfate sulfotransferase assay by coupling
      with sulfite reductase and O-acetylserine(thiol)lyase.
AB  - Adenosine 5'-phosphosulfate (APS) sulfotransferase is thought to be an enzyme
      that transfers the sulfo-group of APS to a carrier compound with a thiol group in
      the assimilatory sulfate reduction pathway of higher plants. We developed a
      rapid, non-radioactive assay for APS sulfotransferase. Sulfite released by APS
      sulfotransferase reaction in the presence of excess dithiothreitol was further
      converted to cysteine by coupling with yeast sulfite reductase and cabbage O
      acetylserine(thiol)lyase. The cysteine thus formed was measured colorimetrically.
      By this method, 5 to 300 nmol of sulfite could be assessed. When the method was
      applied to APS sulfotransferase, the enzyme activity was APS-dependent with the
      partially purified enzyme. We could also detect APS sulfotransferase activity in
      some higher plants by this method.

PMID- 9145522
TI  - Changes in PAF (platelet-activating factor) production during cell cycle of yeast
      Saccharomyces cerevisiae.
AB  - Yeast Saccharomyces cerevisiae cells were cultured synchronously and the change
      of platelet-activating factor (PAF) production during the cell cycle was
      investigated at each phase of the cycle. The basal PAF contents of diploid
      AKU4103 cells in G1 and M phases were higher than those of cells in S phase. Both
      diploid and haploid strains showed the same level of PAF production in response
      to the calcium ionophore A23187. A23187-stimulated PAF productions of cells in G1
      and M phases were about 20 times higher than that of cells in S phase. The
      contents of PAF precursor in G1 and M phases cells of AKU4103 were higher than
      those in S phase cells, and the ratio of A23187-stimulated PAF to the precursor
      was highest in G1 phase cells. We also examined the change in a PAF-synthesizing
      enzyme, acetyltransferase, activity during the cell cycle using a microsomal
      fraction. Specific activity was the highest at G1 phase, and total activity was
      higher at M phase. The enzyme activities of cells in S phase of strains AKU4103
      and RAY-3Aa were one-third and one-tenth of those in G1 phase of corresponding
      cells, respectively. These results suggest that PAF production was higher at G1
      and M phases and lower at S phase, and changes in PAF productivity during cell
      cycle were related to the precursor contents and the synthesizing enzyme
      activities in those cells. These data suggest that PAF may control the cell cycle
      phase in budding yeast.

PMID- 9145523
TI  - Purification and characterization of extracellular poly(beta-D-1,4-mannuronide)
      lyase from Dendryphiella salina IFO 32139.
AB  - An extracellular endo poly(beta-D-1,4-mannuronide) lyase of Dendryphiella salina
      IF 32139 was purified to homogeneity by Q Sepharose FF and Sephacryl S-200 HR
      column chromatographies. The purified enzyme had a molecular weight of 35,000 by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis and an isoelectric
      point of 3.65 by isoelectric focusing. The optimum pH and temperature for enzyme
      activity were pH 5.0 and 45 degrees C, respectively. The enzyme was stable from
      pH 4 to 10 and at temperature below 40 degrees C. Some divalent cations, Ca2+,
      Mn2+, and Zn2+, increased the enzyme activity. Hg2+ and NBS strongly inhibited
      the activity. This enzyme susceptibly degraded poly-M, produced a wide range of
      4,5-unsaturated oligomannuronic acids, and further degraded these unsaturated
      oligomannuronic acids to produce the unsaturated monomer and dimer as final
      products.

PMID- 9145524
TI  - Inhibition of aldose reductase and sorbitol accumulation by astilbin and
      taxifolin dihydroflavonols in Engelhardtia chrysolepis.
AB  - Dihydroflavonol taxifolin and its glycoside, astilbin, from Engelhardtia
      chrysolepis inhibited rat lens and recombinant human aldose reductase. Taxifolin
      also inhibited sorbitol accumulation in human red blood cells. Furthermore, this
      dihydroflavonol aglycone maintained the clarity of rat lens incubated with a high
      concentration of glucose. These dihydroflavonols may be effective for preventing
      osmotic stress in hyperglycemia.

PMID- 9145525
TI  - Cloning and sequence analysis of cDNA encoding endopolygalacturonase I from
      Stereum purpureum.
AB  - Endopolygalacturonase (endoPG) I was obtained from Stereum purpureum by an
      improved easier purification procedure. It was found that EndoPG I consisted of
      three glycosilated proteins with the same isoelectric point and different
      molecular masses, 42, 45, and 48 kDa, respectively. However, the enzymatic
      deglycosilation product of endoPG I gave a single band at the position
      corresponding to 39kDa on SDS-PAGE. Furthermore, the N-terminal amino acid
      sequences of three endoPGs were identical one another up to 20 residues. A cDNA
      library was constructed and positive cDNA clones encoding endoPG I were isolated
      by using antibody raised against the purified endoPG I. Nucleotide sequence
      analysis of the cDNA disclosed a 1212-bp open reading frame that encoded 403
      amino acid residues. The N-terminal amino acid sequence (residues 1-20) of endoPG
      I coincided with the deduced amino acid sequence starting from the 25th residue.
      Therefore, the sequence of the first 24 residues represented a signal peptide and
      the remaining sequence, consisting of 379 residues, was the mature protein with
      molecular mass of 39.1 kDa. The deduced sequence of endoPG I showed 30-45%
      similarity in comparison with those of bacterial and fungal endoPGs, and the
      sequence of putative active site residues reported for the endoPGs was highly
      conserved in the sequence of endoPG I.

PMID- 9145526
TI  - Quantitative study of yeast growth in the presence of added ethanol and methanol
      using a calorimetric approach.
AB  - Using a calorimeter with 24 sample units the heat evolved during incubation of
      yeast cultures at 30 degrees C was detected in the form of growth thermograms.
      Ethanol and methanol added to the culture medium produced changes in the growth
      thermograms that could be analyzed to calculate the 50% inhibitory concentration
      (Ki) and minimum inhibitory concentration (MIC). Correlation of the heat
      evolution curves with the number of cells and the turbidity of the culture was
      found to be very good. It was found that addition of ethanol and methanol up to
      7.65% had clear effects of inhibition on growth of all yeast strains studied,
      reducing the growth rate constant and delaying growth. However, the amounts of
      ethanol produced from the nutrients available in the culture vial was only little
      affected by the initial addition of up to 7.65% (v/v) of ethanol or methanol in
      the medium.

PMID- 9145527
TI  - Secretory production of erythropoietin and the extracellular domain of the
      erythropoietin receptor by Bacillus brevis: affinity purification and
      characterization.
AB  - Bacillus brevis secretes a large amount of cell wall proteins into the culture
      medium. For construction of Bacillus brevis expression-secretion vectors of human
      erythropoietin (EPO) and the extracellular domain of mouse erythropoietin
      receptor (sEPOR), cDNA for each mature form was inserted into a plasmid
      containing the promoter region and the signal-peptide encoding region of a cell
      wall protein. Culture supernatants of transformants were affinity purified using
      a monoclonal antibody-fixed gel for EPO and and EPO-fixed gel for sEPOR. The
      affinity purification efficiently removed unwanted proteins, giving samples with
      sufficiently high purity to analyze amino acid sequences of N-terminal regions
      and biological activities. Combination of this secretory production and affinity
      purification may facilitate isolation of a large amount of pure EPO and sEPOR,
      and is useful for further understanding the molecular mechanism of interaction
      between EPO and EPOR.

PMID- 9145528
TI  - The amino acid sequence of mitogenic lectin-B from the roots of pokeweed
      (Phytolacca americana).
AB  - The complete amino acid sequence of pokeweed lectin-B (PL-B) has been analyzed by
      first sequencing seven lysylendopeptidase peptides derived from the reduced and S
      pyridylethylated PL-B and then connecting them by analyzing the
      arginylendopeptidase peptides from the reduced and S-carboxymethylated PL-B. PL-B
      consists of 295 amino acid residues and two oligosaccharides linked to Asn96 and
      Asn139, and has a molecular mass of 34,493 Da. PL-B is composed of seven
      repetitive chitin-binding domains having 48-79% sequence homology with each
      other. Twelve amino acid residues including eight cysteine residues in these
      domains are absolutely conserved in all other chitin-binding domains of plant
      lectins and class I chitinases. Also, it was strongly suggested that the
      extremely high hemagglutinating and mitogenic activities of PL-B may be ascribed
      to its seven-domain structure.

PMID- 9145529
TI  - Synthesis by an alpha-glucosidase of glycosyl-trehaloses with an isomaltosyl
      residue.
AB  - Glycosyl-trehaloses with an isomaltosyl residue were synthesized by alpha
      glucosidase from Aspergillus niger by using maltotetraose as a glucosyl donor and
      trehalose as the acceptor. The one trisaccharide and two tetrasaccharides formed
      were isolated by successive column chromatography. The results of an enzymatic
      digestion, methylation analysis, and 13C-NMR studies indicated that these
      oligosaccharides were alpha-isomaltosyl alpha-glucoside, alpha-isomaltotriosyl
      alpha-glucoside and alpha-isomaltoside. These oligosaccharides were not fermented
      to an acid by Streptococcus mutans, and they effectively inhibited water
      insoluble glucan synthesis from sucrose by glucosyltransferase. In an in vitro
      utilization test with human intestinal bacteria, these oligosaccharides were
      predominantly utilized by Bifidobacteria.

PMID- 9145530
TI  - Characterization of IKI1 and IKI3 genes conferring pGKL killer sensitivity on
      Saccharomyces cerevisiae.
AB  - The Saccharomyces cerevisiae iki mutants show an insensitive phenotype to the
      pGKL killer toxin, and we have cloned some IKI genes by complementation of this
      phenotype [Kishida et al., Biosci. Biotech. Biochem., 60, 798-801 (1996)]. Here,
      we identified and characterized the IKI1 and IKI3 genes. DNA sequencing of the
      genes showed that both have 100% identity with hypothetical genes identified by
      the yeast genome project, YHR187w (481,911-480,985 in chromosome VIII) for IKI1,
      and YLR384c (888,852-892,898 in chromosome XII) for IKI3. Both are novel genes
      with no significant identity with other known genes and they do not belong to any
      homology domain group, gene family, or superfamily. The disruption of IKI1 is not
      lethal, but growth of the disruptant was slower than that of the wild type at all
      temperatures examined. The disruptant was the killer-insensitive phenotype. The
      sequence of the IKI1 gene predicted a hydrophilic protein with a molecular mass
      of 35 kDa (309 amino acids). A 35-kDa protein band was also detected by
      immunoblotting the 25,000 x g pellet fraction of the wild type yeast cell lysate.
      Disruption of the IKI3 gene is also non-lethal and it has the killer-insensitive
      phenotype. Iki3p may contain a transmembrane domain near the NH2-terminal region
      (97-113 residues in a total of 1349 amino acids).

PMID- 9145531
TI  - A novel metalloproteinase, almelysin, from a marine bacterium, Alteromonas sp.
      No. 3696: purification and characterization.
AB  - We have discovered a novel metalloproteinase, which has high activity at low
      temperatures, from the culture supernatant of a marine bacterium. The strain was
      identified as Alteromonas sp. No. 3696. The metalloproteinase, named almelysin,
      was purified to homogeneity from the cultured supernatant at 10 degrees C by two
      column chromatographies. About 20 mg of purified almelysin was obtained from 18.4
      liters of the culture supernatant. The molecular mass of almelysin was estimated
      to be 28 kDa by SDS-PAGE and the isoelectric point was 4.3. The optimum pH for
      activity of almelysin was pH 8.5-9.0 and 6.5 using casein and (7-methoxycoumarin
      4-yl)acetyl(MOCAc)-Pro-Leu-Gly-Leu-(N3- [2,4-dinitrophenyl]-L-2,3
      diaminopropionyl) [A2pr(Dnp)]-Ala-Arg-NH2 as substrates, respectively. Almelysin
      was stable between pH 7.5-8.0 and below 40 degrees C. The optimum temperature for
      the activity was observed to be 40 degrees C using both casein and MOCAc-Pro-Leu
      Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 as substrates. The activity of almelysin was
      inhibited by such metallo chelators as EDTA and o-phenanthroline, while
      talopeptin, phosphoramidon, and SMPI, typical metalloproteinase inhibitors, had
      no effect. Almelysin primarily cleaved the Ala14-Leu15 bond and Phe24-Phe25 bond,
      and secondarily the Tyr16-Leu17 bond in oxidized insulin B-chain. However,
      almelysin could not cleave the His5-Leu6, His10-Leu11, and Gly23-Phe24 bonds,
      which were cleaved by other metalloproteinases. These results indicate that the
      substrate specificity of almelysin is different from other metalloproteinases.
      Interestingly, Alteromonas sp. No. 3696 strain produced another proteinase as
      well as almelysin at 25 degrees C.

PMID- 9145532
TI  - Increase of the protease activity of aqualysin I, a thermostable serine protease,
      by replacing Asn219 near the catalytic residue Ser222.
AB  - Functional role of Asn219 of aqualysin I, a thermostable serine protease from
      Thermus aquaticus, was investigated by using site-directed mutagenesis.
      Replacement of Asn219 with serine increased the catalytic efficiency (kcat/Km)
      for synthetic peptide substrates about twice as much as that of the wild type,
      while threonine replacement caused a slight decrease in the efficiency. Such
      replacements resulted in a significant change of kcat rather than Km, indicating
      that the side chain in the vicinity of the catalytic residue Ser222 affects the
      catalytic rate constant.

PMID- 9145533
TI  - Stimulating effect of xanthene dyes on immunoglobulin produced in vitro by rat
      spleen lymphocytes.
AB  - The effects of food additives on immunoglobulin produced in rat splenic
      lymphocytes were examined. The xanthene dye, Rose Bengal, enhanced IgE
      production, while inhibiting the production of IgG and IgM, at 50 microM. Among
      the xanthene dyes, Rose Bengal having 4 iodine and 4 chlorine atoms exerted the
      highest Ig production-regulating activity in splenocytes, and dihalogenated
      fluorescein, a diiodo compound, exerted similar activity, while the dichloro and
      dibromo compounds did not. These results suggest that halogen atoms, especially
      the iodine atom, in xanthene dyes play an important role in regulation of Ig
      production.

PMID- 9145534
TI  - Spectroscopic analysis of the cytoagglutinating activity of abrin-b isolated from
      Abrus precatorius seeds against leukemic cells.
AB  - The cytoagglutinating activity of abrin-b, a toxic lectin isolated from Abrus
      precatorius seeds, against cultured cell strains derived from acute lymphoblast
      leukemia (ALL) was investigated by visible (VIS) spectroscopy. Upon addition of
      abrin-b, the turbidity at 600 nm of cell suspension decreased and this change
      could be recorded as the cytoagglutination curve. From this curve, the
      cytoagglutination velocity (CV) and cytoagglutination intensity (CI) of each cell
      strain was measured. Each cell strain showed the respective CV and CI values and
      the cell strains derived from the T cell line were strongly agglutinated by abrin
      b compared with those derived from the B cell line. Further, it has become
      apparent that the cytoagglutinating activity increased with an increase in the
      order of the differentiation of cell strains.

PMID- 9145535
TI  - Spasmolytic activity of aurapten analogs.
AB  - Seven coumaric compounds analogous to aurapten were synthesized. Their
      spasmolytic activity against Ba2+, acetylcholine and histamine was evaluated to
      investigate their structure-activity relationship. The results of the bioassay
      demonstrated the important roles of the cis type of double bond at C-2' and the
      epoxide between c-6' and 7'.

PMID- 9145537
TI  - Recognition of osteopontin by rat bone marrow derived osteoblastic primary cells.
AB  - To study the role of osteopontin, we did cell adhesion and ALP assays of rat bone
      marrow osteoblastic cells (RBMO) on collagen Type I and osteopontin surfaces. The
      RBMO proved to adhere much more strongly to the osteopontin and to have higher
      ALP activity on the osteopontin, which suggests that pre-osteoblasts
      differentiate into osteoblasts that form bone by recognizing osteopontins.

PMID- 9145538
TI  - [Primary health care congresses: towards 10,000 from the year 2000].

PMID- 9145539
TI  - Development of computerized storage facilities for twin data: a relational
      database system for a twin register.
AB  - Many twin registers hold information on flat file systems such as those provided
      by statistical packages or spreadsheets. Demographic details may be maintained
      separately from data collected in multiple different studies, leading to
      considerable problems with data consistency, redundancy, and integration. Ad hoc
      requests may be difficult. Implementation of a relational database system permits
      storage and maintenance of all records, simple data entry and validation
      procedures, linking of information from different projects with security of
      access, and the flexibility to provide rapid answers to ad hoc enquiries using
      standard Structured Query Language (SQL). Twin data provide a challenge for
      relational database design which rests on the technique of normalization and the
      use of unique identifiers to access associated groups of variables; for twins,
      "uniqueness" must preserve identification of both the pair and the individual
      twin subjects in the data structure to enable flexible access to and analysis of
      the data. An application on the Institute of Psychiatry Volunteer Twin Register
      (IOPVTR) database is described, through reference to one study of a sample of the
      twins, with simulated data. We show how a balance of adherence to database design
      principles and attention to ongoing clerical and research procedures has been
      used to produce an integrated, flexible, and open-ended system.

PMID- 9145540
TI  - Genetic and environmental influences on child reports of manifest anxiety and
      symptoms of separation anxiety and overanxious disorders: a community-based twin
      study.
AB  - Genetic and environmental influences in the determination of individual
      differences in self-reported symptoms of separation anxiety (SAD), overanxious
      disorder (OAD), and manifest anxiety (MANX) were evaluated in children and
      adolescents for three age groups (8-10, 11-13, and 14-16). Symptom counts for SAD
      and OAD were assessed for 1,412 twin pairs using the children's version of the
      Child and Adolescent Psychiatric Assessment, and MANX scores were based on child
      report from the Revised Children's Manifest Anxiety Scales. Despite significant
      age and gender differences in thresholds of liability for child reports of
      symptoms of SAD and OAD, additive genetic and environmental effects could be set
      equal across age and gender for these variables. For MANX, however, the best
      fitting model was a common effects sex-limitation model with estimates of
      heritability varying dependent upon age and gender. Parameter estimates from the
      ACE models of OAD and SAD showed that additive genetic variation was a necessary
      component in the explanation of individual differences in child-reported symptoms
      of OAD (h2 = .37) across gender, but does not appear to be a major contributor to
      the explanation of individual differences in symptoms of SAD reported by
      children. Shared environmental effects (c2 = .40) were found to play a moderate
      role for SAD but could be dropped from the model for OAD and from all of the age
      groups for MANX, although the parameter approached significance among 11 yr to 13
      year-old males.

PMID- 9145541
TI  - No association between general cognitive ability and the A1 allele of the D2
      dopamine receptor gene.
AB  - Berman and Noble (1995) reported significantly reduced visuospatial performance
      in children with the TAQI A1 allele of the D2 dopamine receptor (DRD2) gene.
      Given that visuospatial performance loads highly on an unrotated principal
      component indexing general cognitive ability, we tested the association between
      DRD2 and WISC-R IQ comparing 51 high-IQ, 51 average-IQ, and 35 low-IQ children in
      the IQ Quantitative Trait Loci (QTL) Project. No statistically significant
      association between the TAQI A DRD2 alleles and IQ was found. Given that a
      statistically significant portion of genetic variance for specific cognitive
      abilities is independent of general cognitive ability, it is possible that the
      TAQI DRD2 association is specific to visuospatial performance and independent of
      general cognitive ability.

PMID- 9145542
TI  - The D2 dopamine receptor (DRD2) gene and family stress; interactive effects on
      cognitive functions in children.
AB  - TaqI A D2 dopamine receptor (DRD2) alleles, family stress, and cognitive markers,
      including visuospatial ability (Benton's Line Orientation) and event-related
      potentials (P300 amplitude and latency), were obtained in preadolescent boys of
      alcoholic and nonalcoholic fathers. In the presence of the DRD2 minor allele
      (A1+), the Family Stress score negatively correlated with the Line Orientation
      score and P300 amplitude. No significant correlations were found in boys lacking
      this allele (A1-). The interaction of the A1+ allele and the Family Stress score
      produced significant regression coefficients for both Line Orientation score (p =
      .002) and P300 amplitude (p = .04). Together, these two cognitive markers account
      for 37% of the variance in the Family Stress score of 47 A1 allele boys (p =
      .0002) but less than 1% in 71 A1- allele boys (p > .9). This provides the first
      evidence of a specific gene-environment interaction involving human cognitive
      functioning.

PMID- 9145543
TI  - Additive effects of older brothers and homosexual brothers in the prediction of
      marriage and cohabitation.
AB  - Research has shown that male homosexuality tends to cluster in families and that
      homosexual males have, on average, a greater number of older brothers than do
      heterosexual males. This study investigated whether the former, between-families
      effect and the latter, within-families effect are additive. The subjects were 717
      full siblings over age 40 reported by 343 heterosexual and homosexual male
      probands examined in Southern Ontario in 1994-1995. The sibling's history of
      legal marriage or cohabitation in a heterosexual relationship was taken as a
      proxy variable for sexual orientation. There were no significant findings for the
      female siblings. As expected, the never-married male siblings were more likely to
      come from the sibships of the homosexual probands, and they had a greater average
      number of older brothers. A bootstrapped logistic regression analysis showed that
      an additive model best explained the male siblings' data. The results suggest
      that the familial aggregation of male homosexuality cannot be explained by the
      birth order effect and that older brothers and family membership reflect separate
      influences on sexual orientation or sexual orientation-correlated behavior.

PMID- 9145544
TI  - Short-term selective breeding as a tool for QTL mapping: ethanol preference
      drinking in mice.
AB  - Short-term selective breeding starting from an F2 intercross of two inbred
      strains is a largely unexploited but potentially useful tool for quantitative
      trait locus (QTL) mapping. The selection lines can also serve as a valuable
      confirmation test of recombinant inbred (RI) QTL results when the same two
      progenitor strains are used. Starting from an F2 from a C57BL/6J (B6) X DBA/2J
      (D2) cross (B6D2F2), this approach was used in a population of approximately 72
      mice per generation bidirectionally selected for two-bottle choice 10% ethanol
      (alcohol) preference for four generations. The high-preference line diverged
      significantly from the low line in the first generation with a realized
      heritability of .32. By generation 4, the preference ratios in the high line were
      double those seen in the low line. Regions of the genome previously implicated by
      BXD RI QTL analysis as containing QTLs were searched using microsatellite
      markers. The test for the presence of QTLs was based on the divergence of marker
      allele frequencies in the two oppositely selected lines significantly exceeding
      that expected from random (genetic) drift and allele frequency estimation error.
      Combining the BXD and two-way selection line results, the most probable QTL was
      found on chromosome 3 (near the adhl locus; LOD approximately 2.9), other
      probable QTLs were found with LOD 2.4-2.6.

PMID- 9145545
TI  - Hippocampal morphology and open-field behavior in Mus musculus domesticus and Mus
      spretus inbred mice.
AB  - Mus spretus is extensively used in interspecific mouse backcross analyses
      employed to generate genetic linkage maps. However, little is known about its
      behavior and neuroanatomy, phenotypes for which large interstrain differences
      have been observed in Mus musculus domesticus. Behavioral and hippocampal
      neuroanatomical variables were measured in adult male mice from the inbred
      strains C57BL/6J (Mus musculus domesticus) and SEG (Mus spretus). Clear
      differences were found for behavioral responses to novelty in an open field, SEG
      being much less active than C57BL/6J. Morphometrical analysis of hippocampal
      terminal fields, visualized with Timm's stain, revealed strain differences only
      for the size of the intra- and infrapyramidal mossy fiber terminal fields, which
      were about 3 x larger in C57BL/6J than in SEG. In addition, absolute left-right
      differences were larger in SEG for the stratum radiatum and stratum oriens. In
      spite of these behavioral and neuroanatomical differences, the phenotypical
      scores obtained for SEG do not exceed the range observed for Mus musculus
      domesticus inbred strains.

PMID- 9145546
TI  - Success in mating: a coordinated approach to fitness through genotypes
      incorporating genes for stress resistance and heterozygous advantage under
      stress.
AB  - Natural populations are normally exposed to substantial environmental stress. In
      these circumstances, an association occurs between success in mating and extremes
      of sexual ornaments, rapid development, long life span, and low fluctuating
      morphological asymmetry. This association between important fitness traits
      depends on high metabolic efficiency underlain by genes for stress resistance and
      heterozygous advantage. In particular, the high energy demands from the
      development and maintenance of sexual ornaments imply that the "good genes"
      favored in the sexual selection process should be stress resistant. However, the
      generalized heterozygous advantage under stress suggests that many interacting
      genes are involved in promoting metabolic efficiency, so that the "good genes"
      approach should be replaced by a "good genotypes" approach. This "good genotype"
      approach has predictive power for incorporating additional fitness traits,
      especially where metabolic consequences can be perceived.

PMID- 9145547
TI  - Genetic mediation of the correlation between peripheral nerve conduction velocity
      and IQ.
AB  - Variation in peripheral nerve conduction velocity (PNCV) and intelligence was
      studied in 18-year-old Dutch twins. It has been suggested that both brain nerve
      conduction velocity and PNCV are positively correlated with intelligence (Reed,
      1984) and that heritable differences in nerve conduction velocity may explain
      part of the well-established heritability of intelligence. The relationship among
      IQ, obtained with the Wechsler Adult Intelligence Scale, and median nerve PNCV
      was examined in 159 twin pairs. Genetic analyses showed a heritability of 81% for
      IQ and 66% for onset PNCV. The small but significant phenotypic correlation
      between IQ and onset PNCV (.15) was entirely mediated by common genetic factors.
      Analyses of differences scores for PNCV of this study and PNCV from the same
      subjects collected at age 16 suggest that there might still be development in
      PNCV in this age interval. This maturation is highly controlled by genetic
      factors. It is suggested that variation in IQ that is associated with nerve
      conduction velocity becomes apparent only after the developmental processes in
      peripheral nerves are completed. This is in line with the suggestion of
      increasing heritability of IQ in adulthood.

PMID- 9145548
TI  - Effects of censored variables on family studies.
AB  - In the present paper effects of censored variables on estimates of genetic and
      environmental influences were studied. Analytic results showed with 50%
      censoring, about 15-20% of the variance may be attributed to the wrong source and
      that this amount increases rapidly with more than 70% censoring. Censoring
      effects on comparisons between different genetic studies, subgroups within a
      study (e.g., sex or age groups), or different behaviors (e.g., the heritabilities
      of delinquency and depression) were also examined. Results indicated that
      censoring may be quite influential for these kinds of comparisons. For instance,
      it was demonstrated that, especially for unstandardized solutions, small initial
      group differences in means can lead to seriously biased conclusions concerning
      the resemblance in biometric parameters. Finally, a stimulation study supported
      the applicability of the general analytical results and showed that summed scores
      of censored Likert-type items may be seriously affected by censoring.

PMID- 9145549
TI  - The use of likelihood-based confidence intervals in genetic models.
AB  - This article describes the computation and relative merits of likelihood-based
      confidence intervals, compared to other measures of error in parameter estimates.
      Likelihood-based confidence intervals have the advantage of being asymmetric,
      which is often the case with structural equation models for genetically
      informative studies. We show how the package Mx provides confidence intervals for
      parameters and functions of parameters in the context of a simple additive
      genetic, common, and specific environment threshold model for binary data.
      Previously published contingency tables for major depression in adult female
      twins are used for illustration. The support for the model shows a marked skew as
      the additive genetic parameter is systematically varied from zero to one. The
      impact of allowing different prevalence rates in MZ vs. DZ twins is explored by
      fitting a model with separate threshold parameters and comparing the confidence
      intervals. Despite the improvement in fit of the different prevalence model, the
      confidence intervals on all parameters broaden, owing to their covariance.

PMID- 9145550
TI  - Age changes in the causes of individual differences in conservatism.
AB  - Age-related changes are analyzed in the correlation of 3416 monozygotic and 3780
      dizygotic U.S. twin pairs aged between 9 and 75+ years for conservatism scores
      derived from a 28-item social attitude inventory. The effects of the shared
      environment are overwhelming in twins aged 20 years or younger. In older twins,
      genetic effects appear to play a larger role. A more dynamic conception of the
      interaction between genes and environment in the development of complex human
      differences is needed.

PMID- 9145551
TI  - A simple method to calculate resolving power and confidence interval of QTL map
      location.
AB  - "Resolving power" is defined as the 95% confidence interval for quantitative
      trait locus (QTL) map location that would be obtained when scoring an infinite
      number of markers in a given constellation of a marker-QTL mapping experiment.
      Resolving power can serve as a close estimate of the confidence interval of QTL
      map location, as well as a guide to the lower efficient limit of marker spacing
      in an initial marker-QTL mapping experiment. In the present study, an extensive
      series of simulations was carried out to provide estimates of resolving power,
      for backcross (BC) and F2 designs, over a wide range of experimental sizes and of
      gene effects and dominance at the QTL. From the simulation results, the
      remarkably simple expressions, 3000/(mNd2) (where m = 1 for BC and m = 2 for F2;
      N = population size, and d = allele substitution effect) and 530/Nv (in terms of
      v, the proportion of variance explained), were obtained for estimating resolving
      power. These expressions can provide a convenient guide to planning marker
      spacing in BC and F2 marker-QTL linkage experiments and for placing confidence
      intervals about QTL map location obtained in such experiments.

PMID- 9145552
TI  - Genetic and developmental influences on infant mouse ultrasonic calling. I. A
      diallel analysis of the calls of 3-day olds.
AB  - Ultrasonic calls produced by young mice reliably elicit investigation and
      retrieval by adults. While there are large individual differences in the
      characteristics of these calls, little work has been done to partition that
      variation. We completed a 4 x 4 diallel cross and Hayman analyses on several
      characteristics of these cries. The major result was the detection of directional
      dominance toward a higher rate of calling, longer calls, and calls of lower
      overall frequency with a greater bandwidth. Within the context of biometrical
      genetic theory, we conclude that calls with such characteristics may have
      important fitness value. Extending this idea, we propose that within the
      population sampled for this study (the animals of the four inbred strains and 12
      F1 hybrid groups), the calls most effectively eliciting investigation and
      retrieval would be calls with the average hybrid values of the diallel cross.

PMID- 9145553
TI  - Spurious associations in unreplicated selected lines.
AB  - Often a single pair of lines that has been selected for high and low expression
      of a trait is used as an animal model to study new biobehavioral characters
      thought to be associated with the selected trait. Because of genetic drift at
      many loci, comparisons of High and Low lines on the new character will frequently
      produce significant line differences even when there is no association between
      the selected trait and the new character being studied. In the absence of
      replicate lines to estimate the degree of genetic drift, effect size can be used
      to reduce the number of false-positive associations between the original selected
      trait and the new character. When the heritability of the new character exceeds
      .40 and the inbreeding coefficient within the selected lines is moderate, High-
      and Low-line means on the new character will frequently differ by at least one
      phenotypic SD, but not often differ by more than two SDs, in the absence of any
      relationship between the selected trait and the new character. If the selected
      lines are highly inbred, drift effects are greater, resulting in more false
      positive associations. Situations posing special difficulty in the absence of
      replicate lines include the study of characters with low heritability relative to
      the selected trait and cases in which the lines do not differ greatly on the
      original selected trait. Studies using selected lines should always report
      inbreeding coefficients of the generations being studies, relative to the base
      population from which the lines were derived.

PMID- 9145554
TI  - Behavioral reactivity to social and nonsocial stimulations: a multivariate
      analysis of six inbred rat strains.
AB  - Male rats from six inbred rat strains (Spontaneously Hypertensive Rat, Wistar
      Kyoto, Brown Norway, Wistar Furth, Fischer 344, and Lewis) have been compared for
      their behavioral reactivity when placed in several nonsocial (elevated plus-maze,
      open field) and social (social interaction in aversive and neutral environment,
      resident-intruder test, chronic social stress) settings. In addition, a factorial
      analysis was performed to assess how the variables measured in these different
      tests related to each other. Besides significant strain-related differences in
      all tests, the factorial analysis showed that, in nonsocial environments, the
      strains contrasted essentially along two independent behavioral traits, the
      propensity to approach or avoid an aversive stimulus and general motor activity
      in novel environments (two indices of emotionality). In the social settings,
      marked interstrain differences were observed regarding the expression of
      aggressive behaviors but these differences were not related to the respective
      levels on the two nonsocial components of reactivity. Furthermore, large genetic
      differences were observed in variations of body weight induced by a chronic
      social stressor paradigm. The factorial analysis suggested a lack of relationship
      between the effect of social stressors on body weight and the measures of
      emotionality and general activity obtained in the nonsocial tests. Conversely,
      these variations were influenced by the levels of aggressiveness and sociability.
      Taken together, these results show (i) that the behavioral variability observed
      in rats in social and nonsocial environments, is influenced by genetic factors
      and (ii) that the behavioral reactivity to social stimulations is a specific
      feature, dissociable from the levels of the different components of emotionality
      (approach/avoidance and general activity) as evaluated by the behavioral
      responses to nonsocial settings.

PMID- 9145555
TI  - Analysis of recent literature concerning relaxation and imagery interventions for
      cancer pain.
AB  - A review of literature concerning relaxation and imagery interventions for cancer
      pain is necessary because major review articles have excluded nursing research or
      were written prior to the publication of controlled studies in cancer pain
      conducted by nurses. This review of published nursing/medical/psychological
      literature of adults with cancer pain conducted over the past 14 years (1982-95)
      revealed few controlled studies, weak theoretical frameworks, few complete
      descriptions of the nature of the pain problem, and lack of control over the
      interventions. Most had very small sizes and could not demonstrate significant
      effects. Additionally, the intervention methods and length of the interventions
      were highly variable. Despite these design shortcomings, relaxation and imagery
      appear to reduce the sensory experience of pain, have equivocal effects on
      affective measures, and appear to have no effect on functional status.
      Suggestions for improvement include the need for more experimental studies, more
      complete descriptions of pain, improved statistical reporting, controls over
      adequacy of and compliance to the interventions, use of single interventions, and
      use of more complex measures of affective outcomes. Additionally, the paper
      contains a discussion of the problems of measuring selected outcome variables in
      this type of research.

PMID- 9145556
TI  - Validity of a verbally administered numeric rating scale to measure cancer pain
      intensity.
AB  - The ability to quantify pain intensity is essential when caring for individuals
      in pain in order to monitor patient progress and analgesic effectiveness. Three
      scales are commonly employed: the simple descriptor scale (SDS), the visual
      analog scale (VAS), and the numeric (pain intensity) rating scale (NRS). Patients
      with English as a second language may not be able to complete the SDS without
      translation, and visually, cognitively, or physically impaired patients may have
      difficulty using the VAS. The NRS has been found to be a simple and valid
      alternative in some disease states; however, the validity of this scale
      administered verbally, without visual cues, to oncology patients has not yet been
      established. The present study examined validity of a verbally administered 0-10
      NRS using convergence methods. The correlation between the VAS and the NRS was
      strong and statistically significant (r = 0.847, p < 0.001), supporting the
      validity of the verbally administered NRS. Although all subjects were able to
      complete the NRS and SDS without apparent difficulty, 11 subjects (20%) were
      unable to complete the VAS. The mean opioid intake was significantly higher for
      the group that was unable to complete the VAS (mean 170.8 mg, median 120.0 mg, SD
      = 135.8) compared to the group that had no difficulty with the scale (mean 65.6
      mg, 33.0 mg, SD = 99.7) (Mann-Whitney test, p = 0.0065). The verbally
      administered 0-10 NRS provides a useful alternative to the VAS, particularly as
      more contact with patients is established via telephone and patients within the
      hospital are more acutely ill.

PMID- 9145557
TI  - Distress symptoms and support systems of Chinese parents of children with cancer.
AB  - This study focused on the physiopsychological reactions to the stress of parents
      of children with cancer in China. Eighty-nine families who had a child with
      cancer were recruited into four groups: group A, the child was newly diagnosed
      with cancer; group B, the child was under treatment for cancer; group C, the
      child had relapsed and was not expected to live; and group D, the child with
      cancer had already died. Interviews were conducted in Cantonese. The
      semistructured interviews were conducted in the hospital or in the home. Specific
      questions were asked regarding colds, headaches, dizziness, loss of appetite, and
      weight loss. The Parent Stress Rating Scale (PSRS) and the Parent's Support Scale
      (PSS) were administered. Results indicated that parents most often reported
      symptoms of loss of appetite, weight loss, and sleeping difficulty, followed by
      headache, dizziness, and, least of all, colds. Mothers experience more symptoms
      than fathers. Only in the newly diagnosed group and the under treatment group did
      the fathers report having had more colds than the mothers. Parents rated the
      child's death as having caused the highest stress, followed by the terminal stage
      and the diagnosis. Spouses received the highest rating for being supportive,
      across all groups.

PMID- 9145558
TI  - Explaining different profiles in quality of life experiences in acute and chronic
      leukemia.
AB  - There is a need to understand and explain why quality of life (QOL) is
      experienced and viewed differently by those with acute and chronic leukemia. A
      total of 23 adults with either acute or chronic leukemia were interviewed about
      their experience of QOL. Adults with acute leukemia described QOL as a positive
      attitude to life, whereas those with chronic leukemia described QOL as life
      satisfaction. In order to elucidate why there are differences in their experience
      of QOL, a qualitative text analysis was used. The narrated interviews, tape
      recorded and transcribed verbatim, were interpreted based on the following three
      questions: Why are there differences in these individuals' description of QOL?
      What are they talking about? Which phenomenon are they describing? The findings
      were interpreted, "a feeling of uncertainty," which made the difference to their
      experience of QOL. This uncertainty was expressed in different forms and could be
      seen in different degrees. Uncertainty is an important factor affecting the QOL
      of these adults. Nurses who work with these patients have a major role to play in
      minimizing uncertainty by offering coping skills to deal with feelings and
      improving QOL since QOL is one of the outcomes of nursing care.

PMID- 9145560
TI  - Phenomenological study of nurses caring for dying patients.
AB  - Little is known about how nurses experience caring for dying patients. Yet,
      entering the patient's world often involves dealing with death and dying and is a
      major challenge to oncology nurses. The purpose of this article is to describe
      the shared practices of oncology nurses caring for dying patients. Stories from
      staff nurses on an oncology unit were analyzed using a hermeneutic method to
      identify and describe four themes: knowing the patient, preserving hope, easing
      the struggle, and providing for privacy. The four themes contribute to knowledge
      development about how nurses enter into and experience caring for dying patients.
      The growing body of knowledge previously reported has included descriptions of
      critical behaviors in caring for dying patients, coping strategies nurses used
      when caring for dying patients and their families, and the meaning of oncology
      nursing practice. The four themes described in this article expand our
      understanding of the nurses' experience in caring for dying patients.

PMID- 9145559
TI  - Home visits by community nurses for cancer patients after discharge from
      hospital: an evaluation study of the continuity visit.
AB  - After discharge from the hospital, patients with cancer can have several problems
      at home. In this project, patients with cancer, who at time of discharge from the
      hospital were not indicated for nursing care at home, were offered three home
      visits by a community nurse. A prospective, descriptive study was undertaken to
      assess indicators of usefulness of these "continuity visits." It was registered
      how many and what patients [sex, age, (time of) diagnosis, social support,
      therapy] wanted to receive the visit. Care needs, as mentioned by the patients
      during the continuity visits, were reported after the visit by the community
      nurse. Both patients and community nurses completed an evaluation form after the
      first visit. A continuity visit was offered to 337 patients; 112 patients
      received a first, 50 a second, and 24 a third continuity visit. Older patients,
      patients without social support, and those diagnosed less than half a year before
      more often agreed to received a first visit. Reasons for patients not receiving a
      second or third visit were either that patients did not want one or on the
      contrary they were in need of immediate nursing care or had died before the
      visit. Two weeks after discharge, 93% of the patients experienced one or more
      physical, psychological, or social problems; 70% mentioned a need for
      information; and 47% needed emotional support. Both patients and community nurses
      evaluate the first visit positively. The findings suggest that continuation of
      the offer of the first continuity visit could be useful.

PMID- 9145562
TI  - Genes and inheritance.
AB  - The information gained from the Human Genome Project and related genetic research
      will undoubtedly create significant changes in health care practice. It is
      becoming increasing clear that nurses in all areas of clinical practice will
      require a fundamental understanding of basic genetics. This self-learning module
      provides the oncology nurse with an overview of basic genetic concepts including
      inheritance patterns of single gene conditions, pedigree construction, chromosome
      aberrations, and the multifactorial basis underlying many common diseases of
      adulthood. Normal gene structure and function will be introduced and the
      biochemistry of genetic errors will be described.

PMID- 9145561
TI  - Caring and uncaring encounters within nursing and health care from the cancer
      patient's perspective.
AB  - The aim of this phenomenological study was to explore caring and uncaring
      encounters with nurses and other health professionals from the perspective of the
      person who has been diagnosed and treated for cancer. Through thematic analysis
      of in-depth dialogues with five women and four men in the remission or recovery
      phase of cancer, three major categories regarding caring and uncaring encounters
      were identified. The essential structure of a caring encounter was found to be
      threefold: 1. the nurse/health professional perceived as caring: an indispensable
      companion on the cancer trajectory; 2. the resulting mutual trust and caring
      connection; and 3. the perceived effect of the caring encounter: a sense of
      solidarity, empowerment, well-being, and healing. The essential structure of an
      uncaring encounter is also threefold: 1. the nurse/health professional perceived
      as uncaring: an unfortunate hindrance to the perception of well-being and
      healing; 2. the resulting sense of mistrust and disconnection; and 3. the
      perceived effect of the uncaring encounter: a sense of uneasiness,
      discouragement, and a sense of being broken down. The findings emphasize the
      primacy of competence in professional caring, as well as that of genuine concern,
      openness and a willingness to connect with others. The often devastating effects
      of uncaring encounters on the recipient of nursing and health care raises the
      question whether uncaring as an ethical and a professional problem should perhaps
      be dealt with as malpractice in nursing and health care.

PMID- 9145563
TI  - Australian bat lyssavirus infection in three fruit bats from north Queensland.
AB  - We report the case findings of Australian bat lyssavirus infection in two black
      flying foxes (Pteropus alecto) and one little red flying fox (Pteropus
      scapulatus) from north Queensland between January 1995 and August 1996. Although
      the P. alecto case in January 1995 is the first recognised case of Australian bat
      lyssavirus infection in Australia, this was a retrospective diagnosis made after
      identification of the index case at Ballina in May 1996. Eight persons had
      exposure to the three bats. Serum antibodies to classical rabies virus were
      measured in six of these persons; the only one seropositive was a veterinarian
      who had previously been vaccinated against rabies. Six persons received rabies
      vaccine following exposure. None of the in-contact humans developed signs of
      lyssavirus infection. For people exposed to Australian bat lyssavirus-positive
      bats who have not been scratched or bitten or had mucosal contamination by these
      bats, we suggest a post-exposure regime of five inoculations of the human diploid
      cell inactivated rabies vaccine.

PMID- 9145565
TI  - Communicable diseases surveillance.

PMID- 9145564
TI  - Salmonella in Victoria, 1997: the story so far.
AB  - The Infectious Diseases Unit of the Department of Human Services, Victoria,
      reported an increased incidence of Salmonella infections in early 1997. To 21
      April 1997, 944 notifications had been received, passing the previous year's
      total of 915. Five outbreaks of five separate serovars have been investigated and
      traced to their sources. The outbreaks, their sources and the control measures
      undertaken are described. Further clusters of other Salmonella serovars are being
      investigated.

PMID- 9145566
TI  - Monitoring anticoagulant therapy by measuring haemostatic parameters.

PMID- 9145567
TI  - Atrial fibrillation and embolic complications.
AB  - Clinical records of 136 cardiac patients with atrial fibrillation (AF) followed
      in the cardiac clinic of the Black Lion Hospital were analysed. The mean age of
      the patients was 41 +/- 13 years, with a male to female ratio of 1.0:1.6.
      Rheumatic heart disease (RHD) was found in 66.3%, hypertension in 10.3%,
      cardiomyopathy in 8.8% and ischaemic heart disease in 6.6%. Embolic episodes
      occurred in 26 (19.1%) cases with five deaths. Twenty-one patients had
      cerebrovascular accident while five had femoral artery occlusion. The major cause
      of embolisation was rheumatic valvular heart diseases (65.5%), especially mitral
      stenosis. In order to reduce the high risk of systemic emboli, it is recommended
      that patients with AF and associated recent onset of congestive heart failure,
      previous history of thromboembolism and hypertension should be anticoagulated if
      there are no contraindications.

PMID- 9145569
TI  - Recurrent anterior dislocation of the shoulder.
AB  - Results of recurrent anterior dislocation of the shoulder are reported. The
      procedures used were mainly Putti-Plat in 35 patients; Eden-Hybinette in five
      patients and Webers derotation osteotomy of the humerus in five patients.
      Recurrence rates in the 45 patients reviewed and followed up at three years post
      operatively were: six in Putti-Plat and two in Eden-Hybinette and none in Webers
      osteotomy patients. Clinically, the functional post-operative results were
      "excellent" in 32 patients (71%), "satisfactory" in eight patients (18%); while
      they were "unsatisfactory" in three patients and "poor" in two patients. There
      were no appreciable differences depending on the operative method used.
      Radiologically, the Hill-Sachs defect on the posterolateral aspect of the humeral
      head was seen in 30 patients (67%) while Bankarts lesion of the glenoid rim
      osteoarthritis was seen in five patients (11%), while rotator cuff calcification
      was seen in nine patients (20%).

PMID- 9145568
TI  - Use of biometric embryonic growth parameters as indicator of exposure to a
      teratogen.
AB  - Disturbances in embryonic growth were studied in 233 foetuses harvested on day
      14.5 of gestation, after the administration of various doses of 5 Fluoro-2'
      deoxyuridine (FUdR) to pregnant mice on day 11.0 of gestation. Measurements of
      crown-rump length (CRL) and mean wet body weights showed a significant
      retardation of embryonic growth (p < 0.001), following doses of 30, 80 and 100 mg
      FUdR per kg maternal body weight. Compared to the controls, whole FUdR-treated
      embryos that had been macerated, cleared and double stained with alcian blue 8GX
      plus alizarin red S for skeletal anlage, showed that ossification had not
      commenced in the vertebral bones of tail. All bones in the craniofacial region
      and limbs including the girdles, were smaller, while there were distortions of
      the long bones. The severity of the changes were dependent on the concentration
      of FUdR dose administered. Among the live FUdR-treated foetuses harvested, 95%
      had mesomelic limb defects. The incidence of delay or prevention of palatal
      processes elevation was 79%, 49%, 21% and 30% respectively for 0 mg (control), 30
      mg, 80 mg and 100 mg FUdR doses. The results show that administration of a
      teratogenic agent (FUdR) causes retardation of growth which correlates with
      abnormalities of the secondary palate and limbs. It is proposed that the initial
      screening of potential teratogenic substances in food, such as preservatives or
      colourings, may be carried out by monitoring changes in secondary palate and limb
      development, including biometric growth parameters of an animal model.

PMID- 9145570
TI  - Association of schistosomiasis with cervical cancer: detecting bias in clinical
      studies.
AB  - To investigate if Schistosoma haematobium infection increases the observed
      frequency of cervical cancer, data from literature were analysed in meta-analysis
      fashion. Results reveal that cervical cancer is statistically significantly less
      frequent in the presence of S. haematobium infection. A protective effect might
      be inferred; however, underlying bias in data collection and/or analysis is
      suspected. An approach to detecting bias is given, consisting of: (a) carefully
      stating and assessing the several components of the scientific method and; (b)
      identifying and contrasting the populations hypothesised and sampled. The
      approach is illustrated by searching for bias in the schistosomiasis-and-cancer
      reports. Sampling discrepancies were detected in patient geography, ages, and
      states of health, and suspected in disease prevalence sampled and disease
      prevalence reported. The conclusion is reached that effects of bias in the
      original studies preclude inference of a "protective" effect of S. haematobium
      infection against cervical cancer.

PMID- 9145571
TI  - Predominance of HIV-1 among patients with AIDS and AIDS-related complex in Ghana.
AB  - We determined the prevalence of HIV among AIDS and AIDS-Related Complex (ARC)
      patients seen within one year in two hospitals in southern Ghana. Subjects were
      screened by an ELISA procedure for anti-HIV antibodies. Specific identification
      of the HIV type was done with a particle agglutination (PA) kit. All PA
      determined dual specimens were then confirmed by Western blotting and Pepti-Lav
      1/2 monoepitope kit. Virus isolation was attempted from symptomatic patients by
      co-culturing patient peripheral blood monocyte cells (PBMCs) and CD4+ cell lines.
      PBMCs and HIV isolates were characterised by PCR. By ELISA, 43.5% of the subjects
      (253) had anti-HIV antibodies. Of these, 61 (24%) were HIV-1 positive and 42
      (18.6%) were dually reactive by PA. However, only 19% were confirmed as true
      dually-infected cases by western blotting and Pepti-Lav through all 42 samples
      were HIV-1 positive on the two tests. No subject was infected with HIV-2 alone.
      Three viruses were isolated. By PCR two of them had both HIV-1 and HIV-2 proviral
      sequences while the third virus was HIV-1 only. HIV-1 prevalence now predominates
      over HIV-2 implying a switch in the HIV infection pattern in Ghana. Furthermore
      mixed infections exist. The predominance of HIV-1 infection in Ghana may indicate
      a similar trend in other parts of West Africa.

PMID- 9145572
TI  - Presentation and outcome of HIV-1 infection in hospitalised infants and other
      children in north-eastern Nigeria.
AB  - There is limited information on HIV infection in children in West Africa. This
      prospective case series study was done to determine the size of the problem and
      the feasibility of selective screening for infection based on clinical
      presentation. It involved infants and other children admitted to the Children's
      Emergency Ward and Paediatric Medical Ward of the University of Maiduguri
      Teaching Hospital, Nigeria, from the beginning of September 1992 to the end of
      September 1994. Clinical evaluation followed by serologic tests (ELISA and
      Western blot techniques) was undertaken. Descriptive study; frequencies were
      compared using chi 2 test for Fisher's exact test as appropriate. One hundred and
      ninety nine (10.9%) of 1,822 admissions were screened. One hundred and fifty
      eight (79.4%) were ELISA negative and 17 (8.6%) ELISA and WB positive; a further
      10 (5%) were ELISA positive but WB indeterminate and 14 (7%) were ELISA positive
      but WB negative in 12 or untested in two. All the infections were HIV-1. Sixteen
      (39%) patients (nine WB positive, three WB indeterminate and four ELISA positive
      only) are dead, 14 from HIV-related illnesses, two (4.9]) are alive and 23
      (56.1%) lost to follow up; 11 of the HIV-related deaths involved infants.
      Presence of persistent diarrhoea, prolonged fever, oral thrush,
      hepatosplenomegaly, diagnosis of tuberculosis and severe malnutrition with
      gastroentereritis, and multiple (> 3) diagnosis on admission were significantly
      (p < 0.05) associated with WB confirmed HIV-1 seropositivity and could serve as
      indicators for selective screening. HIV-1 infection in hospitalised infants and
      children has become an important problem in Nigeria, presentation in infancy is
      associated with a high case fatality rate, and the practice of selective
      screening based on clinical presentation would appear to be feasible.

PMID- 9145573
TI  - Utilisation of antimalarial drugs by pregnant women attending the antenatal
      clinic at Muhimbili Medical Centre, Dar es Salaam.
AB  - Two hundred women in early second trimester were recruited in a study to monitor
      the utilisation of antimalarial drugs prescribed for prophylaxis or treatment of
      malaria during their attendance at the antenatal clinic of Muhimbili Medical
      Centre. Information regarding the use of antimalarial drugs was obtained during
      an interview using a structured questionnaire and antenatal cards. The study
      revealed that 51.5% had taken antimalarials for treatment of acute malaria while
      23.5% had taken for prophylaxis. There was thus a total exposure of 75%. most of
      them were exposed to choloroquine (69.5l%). There was no statistically
      significant association between the taking of chloroquine and its presence in
      urine and between the level of education and the taking of chloroquine
      prophylactically.

PMID- 9145574
TI  - Solitary unicameral bone cyst.
AB  - This study discusses the results of the 24 patients who had unicameral bone cyst
      treated by the author surgically and conservatively between 1982 and 1992. The
      patients were sixteen males and eight females giving a male to female ratio of
      2:1. Their ages ranged from two to 34 years with a mean age of 18 years. The long
      bones were commonly affected as follows: humerus in eight patients; femur in six
      patients; tibia in two patients. All were affected on the proximimal part of the
      bones, and there were three cysts found in the calcaneus. The main complaint was
      mild dull pain on the affected site. In some cases the pain was severe and
      associated with inability to use the affected limb. X-ray findings showed
      medullary cavity and adjacent inner cortical destruction with mild subperiosteal
      new bone formation causing an expansile appearance and multiloculation. At
      surgery, an area of bone expansion was found with weakened periosteum and
      underlying thin cortex which easily collapsed on pressure leading to a cavity
      containing yellowish fluid. The wall consisted of a thin membrane with ridges
      which was histologically reported as connective tissue with a few bone spicules.
      Surgical results were graded as "good" in 73% and "poor" in 27% due to recurrent,
      shortening or occurrence of sepsis. The bone metabolism studies and total blood
      count were normal.

PMID- 9145575
TI  - Oral malignancies in Ile-Ife, Nigeria.
AB  - Fifty nine patients with histologically confirmed cases of oral malignant
      neoplasia were included in this study. There was a male preponderance with the
      male to female ratio being 2.5 to 1.0. The average waiting period before
      presentation was 8.9 +/- 6.5 months (range: two to 24 months). Squamous cell
      carcinoma was the predominant variety, 50.8%, of all malignancies recorded. The
      alveolar ridge and the gingivae were the commonest sites accounting for 40.7% of
      all cases. Majority of the patients with squamous cell carcinoma, (80.8%),
      presented with stage IV of this disease. The pattern of oral malignancies in the
      population studied appears slightly different from earlier observations in
      Western Europe and Asia. The necessity to strengthen research on the epidemiology
      of the disease in Nigeria and other African countries is highlighted.

PMID- 9145576
TI  - Heritability of diabetes mellitus in Ethiopian diabetics.
AB  - A prospective case control study was conducted in 859 diabetic probands and 1059
      nondiabetic controls. These were interviewed for history of diabetes mellitus
      among their first degree relatives. The protocol also included second and third
      degree relatives. The prevalence of diabetes mellitus in the first degree
      relatives of cases and controls showed a statistically significant difference (Z
      = 6.7564 and P = 0.00000). Similarly, the prevalence of diabetes among the second
      and third degree relatives of cases and controls differed significantly (Z =
      2.74, P = 0.006). There were 445 non-insulin dependent diabetes mellitus (NIDDM)
      and 414 insulin dependent diabetes mellitus (IDDM) in the diabetic probands.
      There was more family history of diabetes mellitus among the first degree
      relatives of NIDDM than IDDM and the difference is statistically significant (Z =
      4.076, P = 0000). The second and third degree relatives of NIDDM and IDDM also
      differed significantly (Z = 4.05, P = 00005). This study indicates that heredity
      plays an important role in the genesis of diabetes mellitus in Ethiopian
      diabetics.

PMID- 9145577
TI  - Use of Leishmania major derived leishmanin for skin test surveys of visceral
      leishmaniasis in Ethiopia.
AB  - The potential use of Leishmania major derived leishmanin in surveys of visceral
      leishmaniasis (VL) was examined. The study was conducted in Konso sub-district,
      southwest Ethiopia involving 51 VL patients, 18 VL contacts, four localised
      cutaneous leishmaniasis (LCL) cases and 15 healthy controls. Sixty three percent
      of treated VL patients, 44.4% of VL contacts, all of LCL cases and none of
      untreated VL patients were positive to the test. Leishmanin skin test (LST)
      induration sizes of 41 treated VL patients were in the ranges of 0 to 10 mm, with
      a mean of 4.9 mm. The mean induration size and the positive LST rates in female
      patients were found to be significantly lower than in males. The major drawback
      of the antigen in the survey was the relatively smaller and flatter indurations.
      The relationship of LST to gender and leishmanial disease variant is discussed.

PMID- 9145578
TI  - Motor neurone disease in the tropics: findings from Sudan.
AB  - In this clinical study the presentation, electromyography and nerve conduction
      studies were described in different types of motor neurone disease in 28 Sudanese
      patients seen at El Shaab and Khartoum Teaching Hospitals. The three major
      clinical subtypes encountered were amyotrophic lateral sclerosis (n = 19),
      progressive bulbar palsy (n = 7) and progressive muscular atrophy (n = 2). Family
      history of the disease was found in four patients and those mainly presented with
      bulbar symptoms. Sudanese patients were found to have an earlier age of onset and
      a better prognosis of the disease than their caucasian counterparts.

PMID- 9145579
TI  - Aetiology and outcome of non-traumatic altered states of consciousness in north
      western Ethiopia.
AB  - Awareness of the relative prevalence of diseases causing altered states of
      consciousness (ASC) in a particular geographic locality could greatly facilitate
      the approach to patient management. This prospective study has, therefore,
      evaluated 202 patients with ASC admitted to the medical wards of GCMS teaching
      hospital in a two year period, between January 1994 and December 1995. ASC was
      defined as a clinical state manifested by conditions ranging from confusion and
      disorientation in person, place and time to stupor and deep coma. History,
      physical examination, limited laboratory tests and course of the patient in the
      hospital were used to identify the aetiology. There were 122 (60.4%) males and 80
      (39.6%) females with male to female ratio of 3:2. Most of the patients, 122
      (60.4%), belong to the age group below 40 years and the median age was 33 years
      (range = 15.84). The median duration of hospital stay was six days (range = 1
      90). The commonest cause was infections, 111 (55%) followed by metabolic
      disorders, 45 (22.3%), structural lesions, 30 (14.9%) and poisoning, seven
      (3.5%). The aetiology was not identified in nine (4.5%) of the patients. Cerebral
      malaria was the commonest infectious cause followed by chronic meningitis and/or
      encephalitis. In hospital mortality rate was 60.4%. Unknown diagnosis, structural
      neurologic and metabolic causes were associated with increased mortality rate,
      with p values of 0.002, 0.009 and 0.015, respectively. The same was true for
      presence of HIV infection, P = 0.02. Since infectious causes are the commonest
      causes in our series, of which most are treatable with a relatively favourable
      outcome, critical evaluation for infections and early intervention is
      recommended. In addition, diagnostic facilities, especially for structural
      central nervous system lesions has to be improved because successful treatment
      and prognosis depends on the identification of a specific aetiology.

PMID- 9145580
TI  - Risk factors for palmo-plantar pustulosis in a developing country.
AB  - Twenty patients with palmo-plantar pustulosis (10 males and 10 females) with a
      mean age of 41 +/- 6.4 years were compared to 20 controls (10 males and 10
      females, mean age 42 +/- 7.2 years, for possible risk factors for palmo-plantar
      pustulosis. No statistically significant difference was found when the two groups
      were compared as regards history of atopy diabetes mellitus and thyroid disease.
      A statistically significant difference was found with regard to cigarette smoking
      (P < 0.001) and presence of joint symptoms (P < 0.01). This pattern, with minor
      variations, is similar to the findings in Western countries. There is a need for
      increased awareness of this association in developing countries. A larger
      population based study will be highly desirable.

PMID- 9145581
TI  - Folie-a-deux: report of two incidents.
AB  - Two incidents of shared delusions are presented, one between two brothers and the
      other between an elderly couple. Their presentation and management are discussed.
      The possible role of projection and overvalued ideas as aetiological factors in
      Nigerians with shared delusions are highlighted.

PMID- 9145582
TI  - Non-puerperal lactation in nutritional rehabilitation: case report.
AB  - An experience in non-puerperal lactation, specifically induced for nutritional
      rehabilitation of a malnourished motherless male infant, is presented from a
      Fulani culture in northern Nigeria where the usual cultural practice is to feed
      such infants with raw cow's milk. The value of non-puerperal lactation in
      nutritional rehabilitation of motherless infants is highlighted and the role of
      adequate psychological preparation and support in successful relactation is
      emphasised.

PMID- 9145583
TI  - Ethnic and religious identity and some age characteristics of alcohol use.
AB  - The sample of the study comprises 618 subjects (316 Christian-Bulgarians and 302
      Muslim-Turks), selected by means of randomized cluster design, and stratified by
      gender, age and place of residence (town vs village). The study used a
      standardized questionnaire specifically developed for it. The study findings
      suggest that the first contact with alcohol and beginning of its regular use
      occur at a younger age in Bulgarians than they do in Turks. A definite trend has
      been found toward earlier first contact and beginning of regular use of alcohol
      in both ethnic groups, but it is more clearly defined in Turks. As a whole
      Turkish ethnic identity and identification with Muslim religious values and
      belief restrict the Turks in their contact with alcohol and are still significant
      factors in restraining alcohol use in their community.

PMID- 9145584
TI  - A study of deliberate self-poisoning in patients with adjustment disorders.
AB  - A sample of 140 patients (34 men and 106 women), hospitalized for deliberate self
      poisoning in a toxicological clinic, was evaluated clinically and by Poldinger's
      risk list for assessment of suicidality. All subjects met the criteria of DSM-IV
      adjustment disorder with no additional Axis I and Axis II comorbidity. 18% of the
      patients had a chronic adjustment disorder. The most common problems on Axis IV
      were those with the primary support group (especially in women). Occupational and
      economic problems were more frequent in men than in women. Most of the studied
      subjects undertook the suicidal attempt impulsively. Suicidal thoughts after
      deliberate self-poisoning persist in only 11% of the patients. The suicidal risk
      measured by Poldinger's risk list for assessment of suicidality was negligible in
      4/5 of the cases. The suicidal risk was higher in patients with chronic
      adjustment disorder and in patients with previous suicide attempts. The most
      represented age group - from 15 to 19 years old showed the highest suicidal risk.
      In women the suicidal risk increased with age. Women with impulsive suicide
      attempt showed a lower suicidal risk than women with a non-impulsive suicide
      attempt. A cathartic and abreactive effect of the suicide attempt was detected,
      but this effect only partially accounts for the relatively low percentage of
      suicidal thoughts after the suicidal act and the insignificant suicidal risk in
      4/5 of the studied subjects.

PMID- 9145585
TI  - A glomus tumour involving the base of the skull.
AB  - The glomus tumours can invade considerable areas of the base of the skull with no
      presenting symptoms or if any they can hardly be guiding. The diagnosis in most
      of the cases is made 5 to 8 years after the onset of the disease. Operative
      treatment may be efficient, but depends on the operability of the case. In our
      case of an inoperable glomus tumour involving the middle and posterior cranial
      fossae, tinnitus appeared as an initial symptom. A week later peripheral facial
      palsy developed. On the 15th day the patient's deglutition was impaired. At the
      end of the fifth month bleeding from the ear appeared. Otoscopy of the outer ear
      showed an irregular, granular formation in the anterior quadrants. The biopsy
      proved alveolar paraganglioma. The size of the tumour was evaluated with
      computerized tomography with and without contrast medium and digital subtraction
      angiography. We report the case because of the long latent asymptomatic course of
      the disease with penetration in the skull base. The first symptoms, manifested at
      the inoperable stage, was suggestive of involvement of the middle and inner ear.

PMID- 9145586
TI  - Early histogenesis in human embryonic liver.
AB  - The present study reports the results of a light microscopy study on the early
      histogenesis of human liver. 18 human embryos in the age range of 6 to 10
      gestational week were studied. The embryos were provided by the Department of
      Obstetrics and Gynecology following an abrasion in normal pregnancy. The
      embryonic liver was studied using conventional histologic technique,
      histochemical methods for lipids and glycogen detection: by enzyme chemical
      methods for establishing the activity of the enzymes lactatedehydrogenase (LDH)
      and succinatedehydrogenase (SDH). The hepatocytes and the basic five types of
      differentiating cells of mesenchymal origin of the liver were studied:
      hemopoietic cells, macrophages, endothelial cells, fibroblasts and smooth muscle
      fibres. Increased activity of the two dehydrogenases and an intensive reaction
      for glycogen in the hepatocytes and myoblasts were observed; for the other cell
      types the reaction was distinctly weaker. The obtained data could be associated
      with the changes in the metabolism of the differentiating cells at the beginning
      of the hepatoorganogenesis.

PMID- 9145587
TI  - A model for standardization of lung function parameters by height.
AB  - Lung function parameters are closely associated with the height of the individual
      and this is the reason why this genetically determined characteristic is present
      obligatorily in the equations giving their reference values. The present work
      studies a large group of models by analysing two groups of healthy individuals -
      20 healthy boys aged 7 to 14 years (10.6 +/- 2.2; mean +/- SD) with a height of
      121 to 170 cm (145.0 +/- 14.2) and 98 healthy men aged 30 to 60 years (44.7 +/-
      6.7) with a height of 159 to 192 cm (171.0 +/- 9.1), all of them non-smokers.
      Statistical analysis shows that standardization of lung function parameters by
      height of healthy individuals is achieved by using a power function of the height
      - FEV1/2.7 and VC/H2.6 for boys aged 7 to 14 years and FEV1/H2.5 and VC/H2.4 for
      men aged 30 to 60 years. The model proposed for children practically neutralizes
      age completely and can be used as a reference equation. The graphic and
      correlation analysis of the residuals obtained as a difference between the actual
      and predicted values of the respective models indicated clearly presence of age
      peculiarities. In men the correlation coefficients between the residuals and the
      height were close to zero, and the residuals themselves were relatively evenly
      distributed around the zero line (a homoscedastic distribution). In children the
      differences scattering increased with the height, i.e. there is a heteroscedastic
      distribution.

PMID- 9145588
TI  - Glanzmann's thrombasthenia in 11 cases of one family.
AB  - We report here the largest family in Bulgaria with Glanzmann's thrombasthenia
      which is inherited in an autosomal recessive manner. Eleven children in four
      successive generations were followed up. Clinically, the disease manifested in
      mucocutaneous haemorrhages. Five of the children died due to severe haemorrhagic
      episodes. The diagnosis was confirmed by haemostasic investigation; in some of
      the children the thrombocytes were examined by electron microscopy. Necessity of
      prenatal diagnosis is suggested.

PMID- 9145589
TI  - Solid tumours in newborns and infants.
AB  - Thirty two cases of solid tumours in newborns and infants were observed by the
      authors over a 15 year period. The most common type of tumours were soft tissue
      tumours (n = 8), neuroblastomas (n = 7), nephroblastomas (n = 5) and germ cell
      tumours (n = 5). Other types of embryonal tumours such as retinoblastoma and
      hepatoblastoma were observed in four children and non-Hodgkin's lymphomas in
      three children. Of 25 children followed up 18 survived. Five children died of
      their tumours and two children died of causes unrelated to their basic disease.
      Analysis of the fate of the patients and the effect of the therapy is made. It is
      concluded that malignant tumours prevail in infancy (90.6% of all cases). The
      percentage of patients treated successfully with insignificant risk for
      consequences from radiotherapy and chemotherapy is also high (72%).

PMID- 9145590
TI  - A study on Q fever among children hospitalized for pneumonia.
AB  - The epidemiological features of Q fever make it of less consequence in childhood.
      However, the disease is quite possible to be contracted at this age due to the
      great number of indirect modes of agent transmission. The disease often escapes
      the attention of pediatricians which results in scantiness of information about
      the incidence rate of Q fever in childhood. The purpose of this study was to
      establish the Q fever incidence among children in the Plovdiv region and the
      disease's medical and social significance. 1706 children aged 0-14 years,
      hospitalized for pneumonia, were subjected to a double serological investigation
      by means of the complement fixation test against the antigen of C. burnetii. A Q
      fever pneumonia was found in 16 children (0.89%) with a mean age of 10.5 years.
      75% of the children were 10-14 years old, and this age group is considered to be
      a risk group. The ration of boy to girls was 1.7:1. 62.50% of the children came
      from rural areas which constitutes the population area risk group. We interpret
      the possible modes of infection - direct and indirect contact with animals, and
      consumption of raw goat's and cow's milk. Because contraction of the disease can
      be realised through indirect routes and the source of infection is not always so
      easily identifiable tests for detecting antibodies against C. burnetii antigen
      should be used in children with non-bacterial pneumonia. This is necessary for
      the pediatric practice.

PMID- 9145591
TI  - Genetic studies on abnormally located chordae in cardiac cavities.
AB  - A sample of 29 patients with abnormally located chordae in the cardiac cavities
      is discussed. The pathologic condition was diagnosed during life time using two
      dimensional echocardiography. The abnormally located chordae were most frequently
      found in the left ventricle, but there were cases in which such chordae were
      found in other cardiac cavities. They numbered one to three and were located in
      groups in the left ventricle or separately in the other cardiac cavities. The
      patients belonged to nine families each one of the families having two to five
      carriers of the anomaly. Such a familial incidence was registered in two,
      sometimes in three generations. The clinical and genealogical data as well as the
      genetic and mathematical testing gives a reasonable basis to assume that this
      familial occurrence of abnormally located chordae is genetically determined and
      has a monogenic autosomal dominant mode of inheritance.

PMID- 9145592
TI  - Reaction of the periosteum to subperiosteal implantation of a foreign body.
AB  - Early cellular reactions of tibial periosteum following its mechanical ablation
      from the bone surface were studied in white female rabbits. Sterile capron nets
      were implanted subperiosteally thus obtaining a model of aseptic inflammation.
      Seven stages in the morphological picture of the reactive process were
      differentiated. THe chronology, cytomorphology and cytophysiology of the stages
      were established by studying the cellular reactions in the reactive exfoliation
      field. Using this experimental setting we show the peculiarities of periosteal
      reaction in an intact and a broken bone.

PMID- 9145593
TI  - Preoperative treatment of children with chronic suppurative otitis media.
AB  - 259 patients with chronic suppurative otitis media were bacteriologically
      assessed. 12 bacterial strains were isolated in 196 of the cases. The most common
      species present was Staphylococcus - 77 (39%) cases, followed by Proteus vulgaris
      isolated in 36 (18%) cases, and Pseudomonas aeruginosa in 33 (17%) cases. The
      flora in 25 cases (18%) yielded two bacterial strains with identical oxygen
      demands, and a mixture of Staphylococcus and Streptococcus in 32%. In 60.6% of
      cases the flora was sensitive to ototoxic antibiotics (gentamycin, kanamycin and
      neomycin), especially to gentamycin - 29.9%. The highest sensitivity of the flora
      to non-ototoxic antibiotics was to chlorocid (in 25.5% of the cases). Topical and
      systemic treatment were administered based on antibiogram and the inflammation
      and the otorrhea were controlled in 91.4% of the cases. No or little effect was
      found in the patients with cholesteatoma (8.6%). A conclusion was made that the
      monoflora was the commonest in the ear effusion (87%), comprising facultative
      anaerobes, present in 63.8%, anaerobes in 18.8%, and aerobes, mainly Pseudomonas
      aeruginosa, in 17.4%. The combined (topical and systemic) treatment based on
      antibiogram is effective in the preoperative management of the inflammation.

PMID- 9145594
TI  - Polycystic ovaries in association with pelvic endometriosis in infertile women
      diagnosed by laparoscopy.
AB  - The author studied the combination of the polycystic ovary syndrome and
      endometriosis in 274 infertile women by laparoscopy. 106 patients were diagnosed
      on clinical criteria as having the polycystic ovary disease which was confirmed
      in 93 of them (87.74%) at the time of the procedure. Coexisting endometrial
      focuses were found in 11 patients (11.83%). The results show that laparoscopy
      should be the modality of choice in the diagnostic work-up in women with
      infertility and clinical symptoms of the polycystic ovary syndrome. Extensive
      scrutiny for endometriosis should be performed in all of these cases since the
      combination of the two conditions is not infrequent.

PMID- 9145595
TI  - Resistance of Vibrio cholerae 01 to nalidixic acid.
AB  - Until 1987 all isolates of V. cholerae 01 at a tertiary care hospital in south
      India were susceptible to drugs commonly used to treat gastroenteritis including
      cholera. Since July 1987 strains resistant to co-trimoxazole have been
      encountered and since October 1995 strains resistant to nalidixic acid are being
      isolated. In this study the latter strains were examined by determining minimum
      inhibitory concentration levels of nalidixic acid as well as norfloxacin, the
      fluoroquinolone extensively used to treat diarrhoea. No cross resistance to
      norfloxacin was found in any of the nalidixic acid resistant V. cholerae 01
      strains.

PMID- 9145596
TI  - Incidence of methicillin resistant coagulase positive & coagulase negative
      staphylococci in blood cultures.
AB  - Isolates of Staphylococcus aureus and coagulase negative staphylococci (CONS)
      from blood culture of bacteraemic patients were studied for methicillin
      resistance is 1993 and 1996. An increase in methicillin resistance among these
      isolates was observed in 1996. In 1993, 32.6 per cent isolates of S. aureus were
      methicillin resistant, this increased to 45.7 per cent in 1996. Methicillin
      resistance in CONS were 1.6 and 14.6 per cent respectively in 1993 and 1996. This
      increase in methicillin resistance may pose therapeutic problems and requires
      more effective drugs based on susceptibility testing of such isolates.

PMID- 9145597
TI  - Extended spectrum beta-lactamase mediated resistance to third generation
      cephalosporins in Klebsiella pneumoniae in Nagpur, central India.
AB  - Out of 66 clinical isolates of Klebsiella pneumoniae, 17 showed resistance or
      decreased susceptibility to third generation cephalosporins (17 to cefotaxime, 16
      to ceftriaxone, and 9 to ceftazidime) while the remaining 49 were sensitive by
      the disc diffusion method. The minimum inhibitory concentrations (MICs) of the
      third generation cephalosporins (3GC) for the strains ranged from 2-128
      micrograms/ml by agar dilution method. Their sensitive phenotypes had zone
      diameters smaller (mean difference 3. 1 mm for ceftriaxone, and 6.5 mm for
      ceftazidime), and MICs > 10 fold higher than the corresponding values in the
      fully sensitive isolates. Resistance to cefotaxime was transferred to recipient
      Escherichia coli K12 strain in 15 isolates. All the resistant isolates were
      sensitive to imipenem but were variably sensitive to aminoglycosides, and
      quinolones. In all 17 resistant isolates extended spectrum beta-lactamase (ES
      beta L) was detected. The sensitivity testing systems may fail to recognise the
      potential ES beta L mediated resistance to 3GC. Hence ES beta L detection should
      be routinely undertaken.

PMID- 9145598
TI  - Antibiotic sensitivity patterns of actinomycetes isolated from patients of
      actinomycetoma.
AB  - The effectiveness of eight antibiotics against 30 human isolates of
      actinomycetoma agents belonging to 7 different species were tested by agar
      dilution and disc diffusion methods to evaluate the susceptibility patterns and
      to study drug resistance among the organisms. It was found that many of the
      isolates had developed partial or complete resistance to conventionally used
      antibiotics like cotrimoxazole, streptomycin and ampicillin, but almost all were
      sensitive to amikacin and ciprofloxacin. The two methods were equally effective
      for detecting sensitivity patterns of the Nocardia isolates.

PMID- 9145599
TI  - Association of enterotoxigenic Bacteroides fragilis with childhood diarrhoea.
AB  - This study was conducted in a hospital setting to determine whether
      enterotoxigenic strains of Bacteroides fragilis (ETBF) were associated with
      childhood diarrhoea. ETBF was isolated from 6 (2.6%) of 226 patients and 3 (1.7%)
      of 172 controls and was found mostly in children between 1-5 yr of age. The
      syndrome associated with ETBF was secretory in nature with watery diarrhoea and
      of mild severity. ETBF may be associated with diarrhoeal illness in children but
      is not a major problem in this part of the country.

PMID- 9145600
TI  - Western blot analysis of serological response in Helicobacter pylori in acid
      peptic diseases.
AB  - A prospective study was undertaken in 70 patients presenting with acid peptic
      disease with the objective of characterising the serological response to
      Helicobacter pylori and finding antigens specific for the serodiagnosis of H.
      pylori infection. H. pylori status was assessed by smear microscopy, rapid urease
      activity, culture and histopathology of endoscopic gastric antral biopsy
      specimens. Serological characterisation was carried out by using western blotting
      of various antigenic components of H. pylori and subsequent enzymatic detection
      of antibodies against them. Four reactive bands in the molecular weight range of
      45-65 kDa were present in all subjects irrespective of H. pylori status. Four to
      six immunoreactive bands in the molecular weight range of 21-45 kDa were found
      only in patients with positive H. pylori status and histopathologically proven
      gastritis. These immunoreactive components may be valuable in specific
      immunodiagnosis of H. pylori infection.

PMID- 9145601
TI  - Production & evaluation of a monoclonal antibody against human myeloperoxidase.
AB  - We describe the production of a mouse monoclonal antibody (H2E1) against human
      myeloperoxidase antigen. After production and characterisation, this antibody was
      compared with commercially available monoclonal antibodies, cytochemical
      myeloperoxidase and previously produced polyclonal antibody. Reaction with
      various cell lines proved that this monoclonal antibody was specific for myeloid
      lineage. This monoclonal showed positivity in 81.8 per cent of acute myeloid
      leukaemias whereas the polyclonal antibody was 100 per cent positive. We found
      that the polyclonal antibody was more sensitive as compared to the monoclonal.
      This is probably due to the lack of recognition of individual epitopes on the
      antigen. We recommend the use of antibodies which have different epitope
      recognition as most specific for myeloperoxidase.

PMID- 9145602
TI  - Thermal, cardiovascular & thermogenic responses to mild cold exposure in
      chronically energy deficient human subjects.
AB  - Thirteen young, male adults were investigated for thermal, cardiovascular and
      metabolic responses to truncal cooling for 40 min. The subjects were divided into
      two groups [well nourished controls (WN) and chronically energy deficient (CED)]
      on the basis of anthropometry and socio-economic status. The CED group had
      significantly greater reductions in peripheral forearm blood flow and surface
      finger tip temperatures on exposure to cold when compared to the well nourished
      controls. The CED group also showed a significant rise in oxygen consumption
      (3.4%), while no thermogenic response was observed in the WN controls. There was
      no fall in deep body temperature in either group. The study suggests that
      chronically energy deficient subjects thermoregulate appropriately on exposure to
      mild cold. The deficiency in insulative body fat is made up for by evoking
      greater peripheral vasoconstrictor responses as well as thermogenic mechanisms.
      The study suggests that on exposure to cold, thermoregulation takes precedence
      over energy conservation in chronically energy deficient subjects.

PMID- 9145603
TI  - Dengue: the killer.

PMID- 9145604
TI  - Correlation of the growth fraction, nucleolar organizer region counts and
      epidermal growth factor receptor with histomorphological prognostic criteria in
      breast cancer.
AB  - A total of 60 cases of breast cancer were studied to find the correlation between
      newer parameters of prognosis viz growth fraction (GF), nucleolar organizer
      region (AgNOR) counts and epidermal growth factor receptor (EGFR) positivity with
      the various histomorphological factors such as tumour size, nuclear grade,
      histological grade and mitoses. Growth fraction measured by Ki67 monoclonal
      antibody varied from 3.6 to 73.7 percent. AgNOR counts ranged from 1.2 to 16.9
      dots per tumour cell nucleus with a mean of 6.26 dots. EGFR positivity was seen
      in 66.7% of cases. Ki67 score correlated with all prognostic variables studied
      except the presence of axillary metastases. AgNOR counts correlated with size of
      tumour, axillary lymph-node metastases and Ki67 score but no correlation was seen
      with histologic or nuclear grade. EGFR positivity correlated strongly with size
      of the tumour and weakly with Ki67 score, AgNOR counts and mitoses.

PMID- 9145605
TI  - Proliferating cell nuclear antigen immunostaining in breast carcinoma and its
      relationship to clinical and pathological variables.
AB  - Tumour proliferative activity of 74 breast lesions was assessed by determining
      mitotic index and immunostaining for proliferative cell nuclear antigen using
      Peroxidase antiperoxidase method. The indices were correlated with
      histomorphology and clinical stage of the disease. Positively stained nuclei and
      mitotic figures were counted per 1000 cells to calculate Proliferating Cell
      Nuclear Antigen (PCNA) and mitotic index respectively. Sixty four cases stained
      positive for PCNA. The index ranged between 0 to 98. PCNA index was significantly
      low in benign lesions as compared to malignant lesions (p < 0.0002). There was a
      linear correlation between the mitotic index and PCNA index. PCNA index also
      showed significant correlation with tumour size and histologic grade; however, it
      had no correlation with axillary lymph node status.

PMID- 9145606
TI  - Early diagnosis of bone biopsies--the role of sediment cytology.
AB  - This study analyses the role of the cytological examination of the sediment of
      the formalin in which bone biopsy specimens are received, in the early diagnosis
      of bone lesions. Of the one hundred lesions studied using this technique, twenty
      six of thirty three malignant lesions (seventy nine percent) could be diagnosed
      as malignant when relevant clinical and radiological data were considered. Sixty
      six benign lesions yielded sparsely cellular smears with benign cell. There was
      one false positive for malignancy. This simple rapid diagnostic technique can be
      used to advantage in the early diagnosis, and treatment planning of bone lesions.

PMID- 9145607
TI  - Role of redchilli (Capsaicin) in the formation of colonic carcinoma.
AB  - The effect of feeding redchilli (Capsaicin) powder on the histopathological
      changes occurring in the colonic mucosa was studied in rats. These animals were
      compared with those treated with a colonic carcinogen 1,2-dimethylhydrazine
      (DMH). Animals fed with redchilli, dimethylhydrazine, dimethylhydrazine plus
      redchilli powder showed polyp and dysplasia, malignant tumour and malignant
      tumour with transitional area of dysplasia.

PMID- 9145608
TI  - Evaluation of luteal phase in normal and infertile women.
AB  - Evaluation of luteal phase function is an important part of fertility evaluation
      in the female. Among fifty clinically identified patients with primary
      infertility certain well-established laboratory methods were used to identify the
      luteal phase defect. These methods included serum progesterone assays,
      endometrial biopsy, vaginal cytology, basal body temperatures and cervical mucus
      scoring, with appropriate controls. Based on both endometrial biopsy which was
      two or more days out of phase and the serum progesterone level of less than 2.5
      ng/ml, luteal phase defect was found in five patients among the 50 patients (10
      percent). It was found that an endometrial biopsy which was well dated showed a
      definite correlation with the progesterone assays and could be considered as the
      most easily performed and reliable indicator, useful in detecting a luteal phase
      defect.

PMID- 9145609
TI  - Study of cryptosporidiosis in a rural area of Maharashtra.
AB  - Human cryptosporidiosis has been reported world wide, both from developed and
      developing countries and from urban and rural areas. Present study is undertaken
      to assess the occurrence of cryptosporidiosis in human and cattle population
      (cows and calves) in and around the rural areas of Loni, district Ahmednagar,
      Maharashtra State. Human stool samples were collected from 220 patients of age
      ranging between newborn to 85 years, attending the Pravara Rural Hospital, Loni.
      The samples were examined using modified Ziehl-Neelsen staining technique. Drug
      samples were also examined from 101 asymptomatic (apparently healthy and non
      diarrhoeic) cows and calves from the same area, to detect Cryptosporidium. Three
      positive cases (1.36%) in human and 11 positive cases (10.89%) in cattle (cows
      and calves) were detected. It is assumed that in rural areas the most likely
      source of human infection is cattle. This is the first report of human infection
      by Cryptosporidium from rural Maharashtra and also the first report of occurrence
      in cattle from India.

PMID- 9145610
TI  - Retinoblastoma--a histologic and immunohistologic study.
AB  - Histopathology and various immunohistochemical markers were studied in 40 cases
      of human retinoblastoma. In histopathology, tumour type, extent and invasion were
      studied. In immunohistochemistry, both glial and neural markers were used to know
      the histogenesis of this tumour. The glial markers, glial fibrillary acidic
      protein and vimentin, were detected in retinal astrocytes and Muller's cells in
      normal retina and perivascular glia in retinoblastoma. The neural marker, neurone
      specific enolase stained neurones in outer and inner nuclear layers in normal
      retina, Flexner-Wintersteiner rosettes in retinoblastoma and tumour cells is
      differentiated retinoblastoma. Another neural marker, neurofilament triplet
      polypeptide stained neurones in inner nuclear layer of normal retina and Flexner
      Wintersteiner rosettes in well-differentiated retinoblastoma. These results
      support the view that retinoblastoma has predominantly neuronal origin.

PMID- 9145612
TI  - Cultivation of Mycobacterium tuberculosis from pleural tissue and its
      histopathology in suspected cases of tuberculous pleural effusion.
AB  - The majority of idiopathic pleural effusion are considered to be of tuberculous
      etiology. The culture of bacilli provide most authentic evidence of disease
      process. This study was carried out on 21 cases of suspected tuberculous pleural
      effusion. The pleural fluid and tissue was subjected for smear examination, and
      cultivation of tubercle bacilli along with pleural biopsy. Overall the diagnosis
      could be made out of 8 (38.09%) cases. The cultivation of Mycobacterium
      tuberculosis from pleural tissue was more sensitive (33.33%) as compared to
      histopathology (19.05%). However, the triad of cultivation of Mycobacterium
      tuberculosis from pleural tissue, pleural histopathology and pleural fluid smear
      examination or culture should be done in each suspected case of tuberculous
      effusion.

PMID- 9145613
TI  - A simple synthetic liquid medium for development of yeast and mycelial form of
      pathogenic species of Candida.
AB  - Thirty two known strains of Candida species were used for evaluation of glucose,
      serine, ornithine, methionine, GSOM medium and its comparison with Lee's medium
      for the production of yeast and mycelial phase at different temperatures and on
      prolonged incubation. No mycelial form was observed when various Candida species
      in GSOM and Lee's medium were incubated at 25 degrees C up to 72 hours.
      Percentage of mycelial forming cells of Candida species were more in GSOM medium
      than Lee's medium in 48 hours at 37 degrees C. Among various species of Candida,
      albicans and C. parapsilosis showed maximum mycelium formation. GSOM medium can
      be used for growing Candida species particularly C. albicans in mycelial phase.

PMID- 9145614
TI  - Fine needle aspiration cytology in the diagnosis of mediastinal seminomas.
AB  - Fine needle aspiration cytology (FNAC) was employed to diagnose 117 cases of
      mediastinal tumours from January, 1985 till December, 1994. Six cases were
      diagnosed as mediastinal seminomas which are rare mediastinal malignant
      neoplasms. All patients had complete resolution of the mediastinal masses after
      external beam radiotherapy. Diagnosis of mediastinal masses by FNAC can spare the
      patients from more invasive diagnostic procedures and help the thoracic surgeons
      to plan immediate treatment.

PMID- 9145611
TI  - Haemolytic Escherichia coli in etiopathogenesis of pyelonephritis in rats--an
      experimental study.
AB  - Of the 26 urinary E. coli strains employed in the present study, 16 were
      haemolytic and 10 were non haemolytic in character. Of the 16 haemolytic strains
      injected through the exposed femoral vein of the rats, 12 showed the lesions of
      pyelitis, pyelonephritis and proliferation of glomerular tuft while 2 showed only
      the lesions of pyelitis and pyelonephritis. It was interesting to note that none
      of the nonhaemolytic strains produced any lesion in the animal. The data
      demonstrated a positive correlationship between haemolytic activity of E. coli
      and pyelonephritis in rats.

PMID- 9145615
TI  - Nephrogenic adenoma of the ureter--a case report.
AB  - We present a case of nephrogenic adenoma, a rare benign lesion arising from the
      ureter. Histologically, it showed the formation of epithelial lined tubules
      resembling the renal tubules. Special Stain demonstrated the presence of
      intraluminal PAS-positive materials.

PMID- 9145616
TI  - Inherited factor X deficiency in two brothers.
AB  - Two brothers born to same parents were diagnosed with inherited factor X
      deficiency of severe type. Clinical presentation in both the cases were
      haemarthrosis. The elder brother was diagnosed in the year 1991 when he was four
      and half years old. Recently the youngest child in the family also presented with
      haemarthrosis at age of one and half years. Diagnosis was made by abnormal
      results of Coagulation factors screening mainly Prothrombin time, Activated
      partial thromboplastin time, Russell's viper venom test, mixing tests factor X
      assay. Both the brothers had Factor X activity less than one percent.

PMID- 9145617
TI  - Malignant interstitial (Leydig) cell tumour of the testis--a case report.
AB  - Interstitial (Leydig) cell tumour of the testis is an extremely uncommon tumour.
      We report one such tumour displaying histologic features of malignancy--large
      size capsular invasion and moderate nuclear pleomorphism in an adult male. The
      tumour also showed crystalloids of Reinke, confirming Leydig cell origin.

PMID- 9145618
TI  - Granular cell tumour (choristoma) of the neurohypophysis--a report of two cases.
AB  - Granular cell tumours of the neurohypophysis are uncommon and only 30 cases are
      documented in the literature till 1994. In this communication, the salient
      clinical and histomorphological features in two patients with granular-cell
      tumour of the neurohypophysis are described.

PMID- 9145619
TI  - Chediak-Higashi syndrome--a case report with ultrastructural and cytogenetic
      study.
AB  - We report the ultrastructural abnormalities of the leukocyte granules and the
      cytogenetic findings in a patient of Chediak-Higashi syndrome (CHS), who
      presented with cutaneous melanosis as the only clinical feature. The diagnosis of
      CHS was established by peripheral smear and bone marrow examination. Chediak
      Higashi syndrome, a rare autosomal recessive disorder is characterized by
      enlarged abnormal organelles in leukocytes and other cells. An interesting aspect
      of our patient was the absence of recurrent infections or any other clinical
      stigmata. Ultrastructurally, the leukocytes and their precursors in the bone
      marrow showed characteristic homogenous and heterogenous giant inclusions of
      variable sizes and shapes. These represent the primary granules which enlarge to
      attain the giant abnormal size by fusion with other primary or secondary
      granules. Cytogenic study of the bone marrow cells showed monosomy of chromosomes
      8 and 17 in 20 percent of the metaphases. Neither the gene nor the chromosomal
      abnormalities specific for CHS have been identified as yet and thus the
      significance of our cytogenetic finding is presently not clear.

PMID- 9145620
TI  - Inflammatory pseudotumour of liver--a case report.
AB  - A rare case of inflammatory pseudotumour of liver in a child is reported. The
      child presented with obstructive jaundice and was considered to have malignant
      tumour of liver clinically and by imaging modalities. Resection of left hepatic
      lobe with the mass was done. Histologically, the lesion consisted of an admixture
      of proliferation of lymphocytes, plasma cells and fibroblasts along with
      vasculitis and variable amount of hyaline fibrosis. Adjacent liver showed
      evidence of biliary cirrhosis and multiple microabscesses. Many of the previously
      reported cases were also diagnosed clinically and radiologically to be malignant
      tumours of liver. The case is reported to create awareness of this rare entity.

PMID- 9145621
TI  - T cell rich and histiocyte rich B cell lymphoma--a case report.
AB  - We report one case of Non Hodgkin's Lymphoma which was classified as Histiocyte
      Rich B cell lymphoma on immunocytochemistry. The diagnosis was difficult on fine
      needle aspiration cytology and routine histopathological examination as the
      infiltrate was composed of reactive lymphocytes and numerous histiocytes
      obscuring the lymphoma cell population. The neoplastic cells were positive for
      CD20(L26-A Pan B marker) and negative for CD15(Leu M1), CD3(Ber H2) and pan T
      cell markers. The histiocytes were positive for CD3(UCHL-1). The patient had a
      rapid downhill course and died. The autopsy showed infiltration in the axillary,
      cervical, mesenteric, para aortic, peri pancreatic and hilar lymph nodes. The
      liver, spleen, bone marrow and kidney also showed lymphomatous infiltration.

PMID- 9145622
TI  - Ectopic decidua in association with adenomyosis presenting as fibroids in
      pregnancy--a case report.

PMID- 9145623
TI  - Subcutaneous and osteolytic rhinosporidiosis.
AB  - A young man presented with multiple Subcutaneous nodules over scalp, hand, feet
      and osteolytic lesions of small bones of hand. Clinically and radiologically he
      was diagnosed as a case of Giant Cell Tumour. Aspiration cytology and biopsy
      proved it to be rhinosporidiosis. Epidemiological study revealed that he perhaps
      contracted this infection as an occupational hazard. This is the third reported
      case of osteolytic lesions due to rhinosporidiosis. Diagnostic dilemmas of
      subcutaneous and osteolytic rhinosporidiosis are discussed.

PMID- 9145624
TI  - Dysembryoplastic neuroepithelial tumour of the central nervous system--a case
      report.
AB  - Dysembryoplastic neuroepithelial tumour (DNT) of the central nervous system is a
      recently recognized entity. We describe the clinical and characteristic
      histomorphological features in a patient with DNT. As this lesion carries a
      favourable prognosis, it becomes essential to make an accurate histopathological
      diagnosis.

PMID- 9145625
TI  - Dengue haemorrhagic fever: an overview.

PMID- 9145626
TI  - The National Medical Association and the Black press: a critical partnership for
      the promotion of excellent health care for all African Americans.

PMID- 9145627
TI  - Female genital mutilation.

PMID- 9145628
TI  - Factors associated with elective Norplant removal in black and white women.
AB  - Premature removal of contraceptive implants (Norplant [levonorgestrel implants],
      Wyeth-Ayerst Laboratories, Philadelphia, Pennsylvania) is a cause of a sizable
      national medical expenditure in the United States. Understanding the factors that
      influence the decision to remove the implants and being able to predict which
      users are likely to elect discontinuation prematurely could provide useful
      information for counseling patients as they are considering contraceptive
      implants so that potentially enormous long-term savings could be achieved. This
      study surveyed 98 women who had Norplant inserted and removed between January
      1991 and December 1994. Data were collected from chart review, and when
      necessary, a questionnaire was used to extract information not found in the
      chart. The chi-squared statistic and t-test were used to compare demographic
      variables. All but one subject received comprehensive pre-implant counseling. The
      main reason given for electively removing the Norplant prematurely was irregular
      menstrual bleeding (60%). Pre-implant counseling did not influence the decision
      for removal. These results indicate the importance of clarifying patients' doubts
      regarding menstrual bleeding irregularities during follow-up visits rather than
      relying on the information patients received during preimplant counseling.

PMID- 9145630
TI  - Primary adenocarcinoma, signet-ring, and transitional cell carcinoma of the
      bladder with penile metastasis.
AB  - This article reports a rare case of primary signet-ring cell carcinoma of the
      bladder with transitional cell and adenocarcinoma variants and metachronous
      metastases to the penis and lungs. This combination of lesions has not previously
      been reported. Together, they portend widespread dissemination and an early
      demise as is frequently the case with signet-ring cell carcinomas arising in
      other organs such as the breast and gastrointestinal tract. The optimal
      therapeutic intervention for this myriad of neoplasms with metastasis to the
      penis has yet to be ascertained because of the rarity of the lesions. Early
      diagnosis and an aggressive surgical approach appear to offer the best chance for
      quality survival and possible cure.

PMID- 9145629
TI  - Primary care paradigm for management of sarcoidosis, Part 2.
AB  - Sarcoidosis is a systemic granulomatous disease of undetermined etiology in which
      the immune system is overstimulated. Management of the patient with sarcoidosis
      entails continuity of patient care far beyond disease, even into remission. Care
      is comprehensive, including all involved organ systems, coordination of specialty
      consultations and services, and includes diagnostic tests. Therapeutic decisions
      are the responsibility of the primary care practitioner. Prognosis of sarcoidosis
      is not uniformly good. Patients can die. Subacute sarcoidosis patients usually do
      not require pharmacologic therapy. Chronic sarcoidosis may require long-term
      treatment for years to indefinitely. Corticosteroids are still the drugs of
      choice and other therapy is now available. Health organizations and private
      nonprofit support groups are available for patient education and assistance.
      Close support must still come from the family unit. Sarcoidosis may occur in
      family members in different cohorts at all ages in life and in any racial or
      ethnic group. The second in a two-part series on management of the patient with
      sarcoidosis, this article describes coordination of care and considers community,
      prevention, and family aspects of the disease.

PMID- 9145632
TI  - Children's and parents' perceptions of children's exposure to violence in urban
      neighborhoods.
AB  - This study examined child and parent perceptions of children's exposure to
      community violence in a sample of 9 to 12 year olds from high- and low-violence
      neighborhoods in Washington, DC. More than 75% of the African-American elementary
      school children sampled indicated that they had witnessed incidents of community
      violence ranging from homicides to nonfatal shootings, physical assaults, gang
      violence, robbery with assaults, and rape in their neighborhoods. Yet, almost
      half of the parents in the study denied that their children had been exposed to
      any community violence. When these discrepancies were examined, results revealed
      that children whose parents were in disagreement regarding their exposure to
      community violence were less likely to experience social support from their
      peers. Parents' possible lack of awareness as to the experience of their children
      may place them at further risk by eliminating the possibility for adult-child
      interaction and guidance regarding their experience with violence in their
      neighborhoods. Recommendations are provided to assist adults in addressing the
      needs of children exposed to community violence.

PMID- 9145631
TI  - Hepatic cells' mitotic and peritoneal macrophage phagocytic activities during
      Trypanosoma musculi infection in zinc-deficient mice.
AB  - The effects of zinc deficiency on hepatic cell mitotic and peritoneal macrophage
      phagocytic activities were examined in mice infected with Trypanosoma musculi or
      immunized with parasitic products. On a full-complement or pair-fed diet,
      infected and homogenate-inoculated mice showed mitotic activity gains of 7.9% to
      80.3% and 6.5% to 99.0%, respectively. Infected and homogenate-inoculated mice on
      a zinc-deficient diet showed 21.8% to 95.7% and 17.2% to 65.2%, respectively,
      more dividing liver cells compared with controls. In comparison to controls,
      macrophages isolated from infected and homogenate-immunized mice on full
      complement or pair-fed diets had phagocytized 13.4% to 31.4% more latex particles
      from day 50 to 80. In the zinc-deficient group, macrophages isolated from
      infected mice had significant numbers of phagocytized latex particles (1.8% to
      38.5%) from day 20 to day 80 compared with controls. The homogenate-immunized
      mice also had increased numbers (18.6 to 30.8%) of phagocytized latex particles.

PMID- 9145633
TI  - What explains black-white differences in survival in idiopathic dilated
      cardiomyopathy? The Washington, DC, Dilated Cardiomyopathy Study.
AB  - We have found race to be an independent predictor of mortality in a preliminary
      analysis of data from an ongoing study of patients with idiopathic dilated
      cardiomyopathy. Our previous, analyses, however, were based on only 12 to 24
      months of follow-up. In the present analysis, which is based on up to 5 years of
      follow-up, we extended our earlier observations and examined whether other
      socioeconomic factors account for the association with race. A total of 128
      patients from five Washington, DC, area hospitals were included in the analysis.
      One hundred three (80.5%) of the patients were black and 25 (19.5%) were white.
      The black patients were less likely to have private health insurance, less
      educated on average, and more likely to have a household income < or = $15,000.
      No racial differences were found in cardiac medication usage, with the exception
      of beta blockers and antiarrhythmics. The cumulated survival among black patients
      at 12 and 60 months was 71.5% and 39.1%, respectively, compared with 92% and
      31.4% among whites. Age, ventricular arrhythmias, and ejection fraction were
      significant predictors of survival in univariate analysis. The univariate
      association with black race was of borderline significance. In multivariable
      analysis using the proportional hazards model, age and ejection fraction were
      significant independent predictors of survival. The association with ventricular
      arrhythmias was of borderline significance. The association with black race,
      which was statistically nonsignificant, was diminished even further by adjustment
      for income and type of health insurance. Thus, the previously reported
      association with black race may be accounted for by socioeconomic factors related
      to access to health care.

PMID- 9145634
TI  - Transient reactive lymphocytosis associated with acute middle cerebral artery
      aneurysmal rupture.
AB  - A 78-year-old female with a prior history of migraine and mild hypertension
      presented to the emergency room with severe headache and mild meningism. The
      patient had transient significant reactive lymphocytosis, and a computed
      tomography scan of the head followed by a cerebral angiogram revealed an acute
      right-sided middle cerebral artery aneurysm rupture. This case illustrates that
      acute changes in the peripheral blood smear may suggest a more sinister cause for
      the presentation such as that of a ruptured middle cerebral artery aneurysm,
      particularly when multiple etiology for the presentation is possible.

PMID- 9145636
TI  - Non-Hodgkin's lymphomas in Pakistan: does late diagnosis fully explain
      transformation into diffuse aggressive lesions?

PMID- 9145635
TI  - Parasitic infections in sickle cell crisis: Nigerian experience.
AB  - Data collected on 150 sickle cell patients in Nigeria were analyzed to determine
      the frequency of parasitic infections in clinical and hematologic crisis. Fifty
      three adult and 97 pediatric patients (mean age: 27.6 years and 9.7 years,
      respectively) were studied. Of these patients, 82 were males and 68 females. One
      hundred thirty-nine had the SS and 11 the SC genotype. Blood samples collected
      from patients on admission for sickle cell-related illnesses were examined
      microscopically for evidence of Plasmodium sp, and stool samples were analyzed
      for presence of any helminth. A total of 102 parasitic infections associated with
      clinical cases of sickle cell crisis were recorded (malaria, 36[35.3%];
      helminths, 49 ([48%]; and malaria and helminths together, 17 [16.7%]). Of the 49
      helminthic infections, 26 (53.1%) were due to Ascaris lumbricoides, 15 (30.6%)
      were due to hookworms, 7 (14.3%) were due to Trichuris trichiura, and 1 (2%) was
      due to Strongyloides stercoralis. The mean hemoglobin levels during clinical
      crisis were 7.1 g/dL for helminths, 6.4 g/dL for malaria, and 6.1 g/dL for
      malaria and helminths together. Reticulocyte counts were 1.4% for helminths, 1.5%
      for malaria, and 1.2% for both malaria and helminths together. Severity and
      duration of the clinical crisis were longer for events associated with a single
      parasitic organism infection than for those with multiple organisms. Routine
      blood smear examination for malaria and stool analysis should be included in the
      laboratory evaluation of individuals with sickle cell anemia in developing
      countries as these infestations could play an important role in precipitating a
      crisis.

PMID- 9145637
TI  - Classification and immunophenotyping of acute leukemias: a prospective study.
AB  - Over a period of 3-1/2 years, 86 cases of acute leukemia were analyzed by
      immunohistochemical (IHC) means on ficoll separated cytospin preparations of
      peripheral blood and/or bone marrow samples. Antibodies included in the panel
      were specific against Tdt, HLA-DR, CD19/CD20/CD22, CALLA (CD10), CD2, CD11C as
      well as against Ig heavy chains. Of 86 cases analyzed, 48 cases were of ALL, (25
      of common pre-B ALL, 15 of pre-B/NULL and 8 of T ALL phenotype), twenty-four (24)
      out of 86 cases were of non-lymphoblastic (AML/AMML) type. In six cases, there
      was suggestion of a mixed lineage, while in 8 cases there was inconclusive
      diagnosis. Mean age was lower in common ALL sub-set of ALL as compared to pre
      B/NULL group (i.e., 8 vs 12 years), while in non-lymphoblastic group it was 36
      years. T cell phenotype was invariably seen in young adults, who usually
      presented with a mediastinal mass.

PMID- 9145638
TI  - Immunophenotypic analysis of non-Hodgkin's lymphoma.
AB  - One hundred and three cases of Non-Hodgkin's lymphoma were evaluated
      immunohistochemically using a panel of monoclonal antibodies which includes
      leucocyte common antigen (LCA), CD45R (Pan-B marker), L-26 (CD 20-Pan-B marker)
      and UCHL-1 (Pan-T marker). Of the total 63 cases (61.17%) showed a B-cell
      phenotype while 40 (38.83%) were of T-cell origin. Most B-cell neoplasms belonged
      to intermediate (79.36%) or high grade (15.87%) according to the International
      Working Formulation (WF). Most T-cell lymphomas were of either intermediate
      (52.5%) or high grade (32.5%) neoplasms. Some T-cell neoplasms presented as
      specific clinicopathological entities like lymphomatoid granulomatosis (2 cases),
      mycosis fungoides (1 case) and AILD type NHL (1 case). In 27 cases the
      immunostaining pattern of two. Pan-B markers i.e., L26 and CD45R was compared.
      L26 staining was expressed in all 27 cases (100% sensitivity) while CD45R showed
      positive reaction in 22 cases (82% sensitivity). UCHL-1 is proved to be a
      sensitive and lineage specific T-cell marker and in 67% cases the staining
      pattern was moderate (+2) to intense (+3). The mean age for the B-cell lymphomas
      was 49 years and 36 years in T-cell neoplasm. Male to female ratio in both types
      of lymphomas was 2:1. The study indicates a high prevalence of T-cell when
      comparing the data from western countries and lower to those from Japan and
      Caribbean countries.

PMID- 9145639
TI  - Bone marrow involvement in Hodgkin's disease: the significance of non
      infiltrative changes.
AB  - We have tried to elucidate the significance of so called non-infiltrative changes
      in order to find their place in the staging procedure particularly in countries
      where facilities for elaborate clinical staging are not available. Seventy nine
      out of 88 patients were classified into 3 groups depending upon the histological
      findings in their bone marrow trephine biopsies. Bone marrow in Group-I (n = 20)
      patients was essentially normal. The established criteria of bone marrow
      involvement were fulfilled in Group III patients (n = 25); while bone marrow in
      Group-II patients (n = 34) showed non-infiltrative changes. The clinical
      presentation, peripheral blood parameters and LDH levels of the 3 groups of
      patients were compared. There was progressive anaemia, neutrophilic leucocytosis
      and increase in ESR from Group I to III. The change was statistically significant
      when Group I was compared with Group II or Group III but non-significant when
      Group II was compared with Group III. It is, therefore, postulated that both
      Groups II and III reflect the bone marrow involvement although the changes
      observed in Group II do not satisfy the previously established criteria for this
      purpose.

PMID- 9145640
TI  - Is carcinoma breast a different disease in Pakistani population?
AB  - Carcinoma of the breast tends to be different in coloured and white races. Is
      this pattern also expressed in Pakistani population? To answer this query we
      carried out a retrospectively study of breast cancer on 193 cases who were
      divided into 2 groups i.e. less than and more than 50 years age groups. In the
      former group, 93% tumours were of grades II or III and approximately 51% were
      estrogen receptors negative. In more than 50 years age group, 75% tumors were in
      grade II and III, with almost 37% being estrogen negative tumors. Majority (75%)
      of the patients had over 6 cms lump with equal number having positive lymph node
      status. All these factors point to the fact that besides presenting late, our
      population has additional unfavourable prognostic factors.

PMID- 9145642
TI  - Clinicoepidemiological features of adult leukemias in Pakistan.
AB  - A total of 113 patients of leukemia, over 15 years of age, were seen in three
      different institutions from July, 1992 to June, 1994. There was an almost equal
      distribution of acute myeloid leukemia (AML) and acute lymphoblastic leukemia
      (ALL) (44 vs 43 cases respectively). Chronic lymphocytic leukemia (CLL) was the
      least common, accounting for 5% of all cases. Mean age in CLL was 59 years.
      Chronic myeloid leukemia (CML) was three times commoner than CLL with a younger
      age distribution (median age was 34 years). We conclude that the
      clinicoepidemiological features of adult leukemias differ considerably from that
      seen in the developed world. However, recruitment of patients needs to continue
      in order to define these features based on a larger patient population.

PMID- 9145641
TI  - Prognostic factors in stage-I breast cancer: a retrospective study.
AB  - We studied the case records of all patients presenting with stage-I breast cancer
      (tumour < 2 cm, no axillary nodes or distant metastases). All clinical and
      pathological features were evaluated and findings were correlated with short term
      treatment failures (local and distant recurrences within 2 years). An early
      recurrence was seen in 28% patients. There was no significant differences in the
      mean age at presentation (44 vs 47 years) or menopausal status (8 Vs 7 years).
      Estrogen receptor status was unknown in all the patients. A positive family
      history of breast cancer was noted in 40% women with tumour relapse against 6% in
      the non-relapsed group. Associated fibrocystic mammary dysplasia was found in 80%
      relapsed cases whereas 60% showed lymphatic invasion and tumour necrosis.
      Vascular invasion was reported in 40% cases. A poorly differentiated histology
      fibrocystic mammary dysplasia, lymphatic and vascular invasion and tumour
      necrosis were poor prognostic factors. It was concluded that adjuvant
      chemotherapy should be given to all patients presenting with stage-I breast
      cancer and showing poor prognostic factors regardless of the menopausal status.

PMID- 9145643
TI  - Cancer in north west Pakistan and Afghan refugees.
AB  - The medical records of all patients attending the Institute of Radiotherapy and
      Nuclear Medicine (IRNUM), Peshawar during 1990 and to 1994 were analysed to
      determine the frequency of most common cancers. There were 13,359 adults with
      biopsy proven cancers of these 10,371 belonged to the North West Frontier
      province (NWFP) and remaining 2,988 were Afghan refugees. In NWFP there were 55%
      males and 45% females, while in Afghan refugees there were 59% males and 41%
      females. Patients whose histopathology was doubtful or not available were
      excluded from the study. The most common male tumours were skin, lymphoma, oral
      cancer, urinary bladder, lung, oesophagus, soft tissue, prostate, brain and
      myeloid leukemia. Among male Afghan refugees the most common cancers were
      oesophagus, skin, lymphoma, oral cancer, soft tissue, myeloid leukemia, stomach,
      urinary bladder, testis and colorectal cancer. Breast cancer was the most common
      cancer in women.

PMID- 9145644
TI  - Sarcomatoid variant of renal cell carcinoma.

PMID- 9145645
TI  - Mikulicz syndrome.

PMID- 9145646
TI  - [The distribution and the characteristics in computed tomography (CT) of the
      lungs in primary Mycobacterium avium complex (MAC) infection].
AB  - We investigated the distribution and the characteristics of the lung lesions of
      patients with primary Mycobacterium avium complex (MAC) infections mainly by
      computed tomography (CT). They admitted to our hospital during the period from
      1984 to 1995 and none of them had a medical history of tuberculosis or other lung
      diseases. The subjects consisted of fifty patients: fourteen male (average age +/
      SD was 66.4 +/- 14.0 year old) and thirty six female (69.0 +/- 11.9 year old).
      Of 50 patients 24 were M. intracellulare infection, 10 were M. avium infection
      and others were not identified. First, by using the ratio of slices with lesions
      on CT to all CT slices from the apex to the base of the lungs, all the patients
      were divided into two groups; a slight group with less than 15.0% (n = 19) and a
      severe group with 15.0% or more (n = 31). Next, the density of abnormal shadows
      in each segment as divided into 5 grades; none (-), minimal (+/-), slight (+),
      moderate (+2) and severe (+3). The grading was done by taking into account the
      grade of distribution, density of lesions and destruction of lung parenchym found
      mainly on CT, and in addition by a standard roentogenographic and tomographic
      features supplemental. The characteristics frequently observed findings on CT in
      primary MAC infection patients were nodular (94%), cavitary (74%), bronchiectatic
      (62%), infiltrative (74%), atelectatic (56%), and pleural-thickened (36%)
      shadows. Comparing the incidence of segmental lesions in MAC infection patients
      by segment, it was higher in right and in left lung, but the difference was
      statistically not significant. As to the number of segments with lesions graded
      from (+/-) to (+3), many segments were infected unexpectedly: the mean value was
      7.7 +/- 1.5 even in the slight group. The proportion of segments with relatively
      severe lesions graded from (+2) to (+3) in each segment was observed, and the
      rate in the slight group was 52.6% in S5, 28.9% in S4, 16.7% in S1 (S1 + 2a, b),
      and 16.7% in S2 (S1 + 2c). In severe group, it was 54.8% in S5, 45.2% in S4,
      46.8% in S1 (S1 + 2a, b) 54% in S2 (S1 + 2c), 27.4% in S3 and 26.2% in S6,
      respectively. The rate of segments with lesions in the lower lobes were less
      frequent especially in the slight group while it was slightly higher in the
      severe group. Speculating the initial lesions in the slight group, it was assumed
      that there might be two types of foci; the one is relatively localized in the
      beginning and the other is a diffuse type with lesions in many segments even from
      its early stage. As to the location of initial lesions, the middle lobe and
      lingula were the most important sites, and the right upper lobe and the left
      upper division were the next.

PMID- 9145647
TI  - [Reliability of Amplicor Mycobacteria test for detection of Mycobacterium
      tuberculosis complex. M. avium and M. intracellulare: a cooperative study among 9
      laboratories].
AB  - The Amplicor Mycobacteria, a PCR-based assay, is a rapid test for the detection
      of Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium
      intracellulare in clinical samples. To estimate the reliability and
      reproducibility of the method, a cooperative blind study was conducted among 9
      laboratories. Materials used for testing consisted of 105 sputum and 30 water
      samples containing known numbers of M. bovis BCG, M. avium, M. intracellulare,
      and samples without bacteria. Only 2 out of the 9 laboratories correctly
      identified the presence or absence of mycobacterial DNA in all 135 samples. In
      sputum samples, 6 out of the 9 laboratories detected mycobacterial DNA in all
      positive samples, and 4 out of the 9 laboratories correctly reported the absence
      of DNA in the negative samples, indicating the need for good laboratory practice
      and development of reference reagents to monitor the performance of the whole
      study, including pretreatment of clinical samples. The main problem was lack of
      specificity rather than lack of sensitivity. From about half of the laboratories,
      false-positive results were reported, however, the ratio was below 6%; 1% (1/106
      sputum samples) in 3 laboratories, 1.9% (2/105) in 2 laboratories, and 5.7%
      (6/105) in one laboratory, respectively. These results indicate that the Amplicor
      Mycobacteria is quite useful for a rapid diagnosis of tuberculosis.

PMID- 9145648
TI  - [Evaluation of mycobacteria growth indicator tube (MGIT) for drug susceptibility
      testing of Mycobacterium tuberculosis isolates].
AB  - Fifty six clinical isolates of Mycobacterium tuberculosis were tested for drug
      susceptibility in Mycobacteria Growth Indicator Tube (MGIT) containing 0.1
      microgram/ml of INH, 1.0 microgram/ml of RFP, 3.5 micrograms/ml of EB and 0.8
      microgram/ml of SM. These results were compared with those obtained by testing
      the same M.tuberculosis isolates by the absolute concentration method using 1%
      Ogawa egg slant containing 0.1 microgram/ml of INH, 10 micrograms/ml of REP, 2.5
      micrograms/ml of EB and 20 micrograms/ml of SM. Fifty six isolates consisted of
      18 pansensitive strains, 27 multidrug resistant strains and 11 single drug
      resistant strains. The results of individual drugs showed excellent agreement
      between the MGIT and the Ogawa methods, and overall agreement rate of the two
      methods were 96.4%. The results were just the same for all drugs in 48 out of 56
      strains studied. The drug resistance could be observed much earlier by the MGIT
      method (mean 5.9 days) than by the Ogawa method (more than 21 days). In
      conclusion, the MGIT system could be a promising new drug susceptibility test
      which might become available in Japan replacing the Ogawa method.

PMID- 9145649
TI  - [Distribution of antigenic glycolipids among Mycobacterium tuberculosis strains
      and their contribution to virulence].
AB  - Tuberculosis is a chronic disease caused by Mycobacterium tuberculosis infection.
      The major pathological changes are immunologically hypersensitive granuloma
      formation due to the local proliferation or infiltration of immune cells.
      However, the mechanism for the development of the disease has not yet been fully
      understood. The first step of infection in intracellular survival in the
      phagocytic cells and this process has been reported to be regulated by cell
      surface glycolipid virulence factors. As genetical heterogeneity of M.
      tuberculosis among strains has been reported recently based on DNA fragmentation
      pattern, I have examined the distribution of cell surface glycolipids (cord
      factor, sulfolipids and penta acyl trehaloses) among the virulent (M.
      tuberculosis H37Rv and M. tuberculosis Aoyama B) and virulent (M. tuberculosis
      H37Ra) strains by two dimensional thin-layer chromatography of silica gel. Seven
      characteristic glycolipid components of the virulent strains were detected and
      separated by thin-layer chromatography of silica gel. Each glycolipid was
      identified by fast-atom-bombardment mass-spectrometry (FAB/MS) analysis of the
      intact lipid and gas-chromatography mass-spectrometry (GC/MS) analysis of the
      fatty acid or the carbohydrate moiety. As the result, molecular weight (m/z,
      1,200-3,000) of each glycolipid was determined clearly by FAB/MS analysis. The
      structure of fatty acids (C16-C40) or mycolic acids (C76-C88) were determined by
      GC/MS analysis. Cord factor (TDM, trehalose 6,6'-dimycolate) and trehalose 6
      monomycolate (TMM) showed strong granuloma forming activity, but other
      glycolipids practically did not. On the other hand, cord factor and trehalose 6
      monomycolate showed phagocytosis inhibition (but showed promotion in the presence
      of complement) and marked inhibition of phagosome-lysosome fusion, while
      sulfolipids showed strong phagocytosis promotion and marked inhibition of
      phagosome-lysosome fusion. Penta acyl trehaloses showed phagocytosis promotion
      but no effect on phagosome-lysosome fusion. Cord factor and trehalose 6
      monomycolate existed ubiquitously among virulent and avirulent strains, while
      sulfolipids and penta acyl trehaloses were detected in only virulent strains (M.
      tuberculosis H37Rv and M. tuberculosis Aoyama B). These results indicate that the
      existence of these toxic glycolipids contributes to the virulence of M.
      tuberculosis, profoundly. It is suggested that these glycolipids play an
      important role as virulence factors in the early stage of infection and
      expression of pathogenicity.

PMID- 9145650
TI  - Looking back to go forward.

PMID- 9145651
TI  - Developmental stages of clinical research programs, Part I.

PMID- 9145652
TI  - Viable fetus vs. drug-abusing mother.

PMID- 9145654
TI  - An asthma day camp.

PMID- 9145653
TI  - The hospitalized child with asthma.

PMID- 9145655
TI  - Planning for pregnancy--a preconception health program.

PMID- 9145656
TI  - Supporting the adoptive family: a developmental approach.

PMID- 9145657
TI  - Caring for pregnant teens and their mothers, too.

PMID- 9145658
TI  - Measuring the effects of redesign.

PMID- 9145659
TI  - A new voice.

PMID- 9145660
TI  - Leukotriene receptor antagonists: the newest in asthma drugs.

PMID- 9145661
TI  - The early history of neurosurgery in New York.

PMID- 9145662
TI  - The early days of microsurgery in Vermont.

PMID- 9145663
TI  - The advent of microsurgery.

PMID- 9145665
TI  - Technical contributions of Leonard I. Malis.

PMID- 9145664
TI  - Leonard I. Malis: an appreciation.

PMID- 9145666
TI  - Basic science contributions of Leonard I. Malis.

PMID- 9145667
TI  - Leonard I. Malis and prophylactic antibiotics.
AB  - Leonard I. Malis introduced important changes in the antimicrobial regimen for
      neurosurgical procedures at The Mount Sinai Hospital. Among Dr. Malis'
      innovations, intraoperative administration of a single dose each of vancomycin
      and gentamicin or tobramicin and constant irrigation of the surgical site with a
      bactericidal antibiotic (streptomycin) led to the elimination of primary wound
      infections during a 20-year period. In a study to locate potential sources of
      microbial contamination in his operating room, this combination of parenteral
      antibiotics was justified, because 36% of patients were at risk for exposure to
      methicillin-resistant Staphylococcus aureus and Gram-negative bacteria.
      Streptomycin as a topical agent was found to be highly efficacious in preventing
      intraoperative growth of potential pathogens cultured from the surgical wound and
      the operating room environment.

PMID- 9145668
TI  - Another look at ventriculosubgaleal shunting procedures.
AB  - Ventriculosubgaleal shunts were available at the turn of the century as a
      treatment for hydrocephalus. Almost 80 years later, Perret and Graf advocated
      such shunting for the temporary decompression of ventricles enlarged by tumors or
      by hydrocephalus. The use of a subgaleal shunt in acute head trauma was first
      published in 1983. No direct measurement of intracranial pressure was attempted
      in 30 cases. Evidence by computed tomography of compressed ventricles and
      cerebral contusion correlated well with elevated pressure. When the Camino
      intracranial pressure monitor became available, the device was inserted before
      placement of the shunt to assess the appropriateness and efficacy of the method
      in 21 patients. An additional 22 cases of intraventricular hemorrhage with acute
      hydrocephalus were treated over a 17-year period. The simple method of shunting
      into the subgaleal space has broad application for the temporary relief of
      increased intracranial or high-pressure hydrocephalus.

PMID- 9145669
TI  - Neuroradiology at the Mount Sinai Hospital.

PMID- 9145670
TI  - Venous architecture of cerebral hemispheric white matter and comments on
      pathogenesis of medullary venous and other cerebral vascular malformations.
AB  - The parenchymal veins, especially the deep medullary veins, of the cerebral
      hemispheres were studied in detail by analyzing the stereoroentgenograms of
      multiple brain slices of postmortem injected brain specimens (injected into the
      internal carotid arteries in 17 cases and into the jugular veins in 12 cases).
      The presence of four zones--the first (or outer), the second (or candelabra), the
      third (or palmate) and the fourth (or subependymal) zone--of venous convergence
      was confirmed within the centrum semiovale, particularly in the frontoparietal
      area. Other venous convergences such as those related to the optic radiation in
      the para-atrial area were also found. Arterial branching zones were also observed
      in the areas similar to those of the medullary veins. It appears that these
      converging zones are created by rapidly growing crossing nerve fiber tracts,
      i.e., projection, commissural, and association fibers which grow rapidly during
      intrauterine and postnatal life. Pathogenesis of medullary venous malformation is
      also discussed from anatomical viewpoint, venoarchitecture of the pial,
      parenchymal, and subependymal veins and of the dural venous sinuses. The
      possibility of a similar mechanism (partial, mild, repetitive venoocclusive
      disease developing over a long period with fluctuating venous pressure) leading
      to formation of most (if not all) cases of medullary venous malformation and in
      some, if not many, cases of cerebral vascular malformations [aside from gene
      abnormality (chromosome 7) in familial cavernous angiomatosis, particularly in
      Hispanic American or other familial hereditary conditions] has been postulated.

PMID- 9145671
TI  - Operative microphotography: a Malis legacy.
AB  - An account of the methods and equipment used by Dr. Malis for the development of
      operative microphotography is presented. Attention to the critical evaluation of
      technology became part of the legacy provided to those he trained. Current
      microphotographic innovations are described.

PMID- 9145672
TI  - The prone-oblique surgical position.
AB  - The prone-oblique surgical position as introduced and used by Dr. Malis at Mount
      Sinai Hospital is presented. The advantages of this position over the prone and
      knee-chest positions are noted. Recommendations for the safe use of the prone
      oblique position are made.

PMID- 9145673
TI  - A biorbitofrontobasal interhemispheric approach for suprasellar lesions.
AB  - Suprasellar tumors including pituitary adenomas and craniopharyngiomas, in the
      case of normofixed or postfixed chiasma and ruptured anterior communicating
      artery aneurysms in the acute stage, can be approached with minimum brain
      retraction, increased exposure, and safe manipulation in the shortest possible
      distance via biorbitofrontobasal interhemispheric approach. Fourteen patients
      with pituitary adenomas, 3 with craniopharyngiomas, 7 with meningiomas, 2 with
      mucoceles, 1 with osteoma, and 3 with ruptured anterior communicating aneurysms
      in the acute stage were operated on, using this approach with excellent results.
      The operative technique and its results are detailed.

PMID- 9145674
TI  - Microneurosurgery in suburbia.

PMID- 9145675
TI  - Radiologic evaluation in patients with head injury.
AB  - Head injury is common. With many excellent imaging techniques readily available,
      radiologic evaluation has become critical in the management of patients with head
      injuries. We review the indications for various imaging studies in patients with
      head injury. In general, a noncontrast computed tomography of the head is the
      study of choice for patients with head injury and should be performed whenever
      there is reasonable suspicion of a serious injury to the brain.

PMID- 9145676
TI  - The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among
      Ashkenazi Jews.
AB  - BACKGROUND: Carriers of germ-line mutations in BRCA1 and BRCA2 from families at
      high risk for cancer have been estimated to have an 85 percent risk of breast
      cancer. Since the combined frequency of BRCA1 and BRCA2 mutations exceeds 2
      percent among Ashkenazi Jews, we were able to estimate the risk of cancer in a
      large group of Jewish men and women from the Washington, D.C., area. METHODS: We
      collected blood samples from 5318 Jewish subjects who had filled out
      epidemiologic questionnaires. Carriers of the 185delAG and 5382insC mutations in
      BRCA1 and the 6174delT mutation in BRCA2 were identified with assays based on the
      polymerase chain reaction. We estimated the risks of breast and other cancers by
      comparing the cancer histories of relatives of carriers of the mutations and
      noncarriers. RESULTS: One hundred twenty carriers of a BRCA1 or BRCA2 mutation
      were identified. By the age of 70, the estimated risk of breast cancer among
      carriers was 56 percent (95 percent confidence interval, 40 to 73 percent); of
      ovarian cancer, 16 percent (95 percent confidence interval, 6 to 28 percent); and
      of prostate cancer, 16 percent (95 percent confidence interval, 4 to 30 percent).
      There were no significant differences in the risk of breast cancer between
      carriers of BRCA1 mutations and carriers of BRCA2 mutations, and the incidence of
      colon cancer among the relatives of carriers was not elevated. CONCLUSIONS: Over
      2 percent of Ashkenazi Jews carry mutations in BRCA1 or BRCA2 that confer
      increased risks of breast, ovarian, and prostate cancer. The risks of breast
      cancer may be overestimated, but they fall well below previous estimates based on
      subjects from high-risk families.

PMID- 9145677
TI  - BRCA1 mutations in women attending clinics that evaluate the risk of breast
      cancer.
AB  - BACKGROUND: To define the incidence of BRCA1 mutations among patients seen in
      clinics that evaluate the risk of breast cancer, we analyzed DNA samples from
      women seen in this setting and constructed probability tables to provide
      estimates of the likelihood of finding a BRCA1 mutation in individual families.
      METHODS: Clinical information, family histories, and blood for DNA analysis were
      obtained from 263 women with breast cancer. Conformation-sensitive gel
      electrophoresis and DNA sequencing were used to identify BRCA1 mutations.
      RESULTS: BRCA1 mutations were identified in 16 percent of women with a family
      history of breast cancer. Only 7 percent of women from families with a history of
      breast cancer but not ovarian cancer had BRCA1 mutations. The rates were higher
      among women from families with a history of both breast and ovarian cancer. Among
      family members, an average age of less than 55 years at the diagnosis of breast
      cancer, the presence of ovarian cancer, the presence of breast and ovarian cancer
      in the same woman, and Ashkenazi Jewish ancestry were all associated with an
      increased risk of detecting a BRCA1 mutation. No association was found between
      the presence of bilateral breast cancer or the number of breast cancers in a
      family and the detection of a BRCA1 mutation, or between the position of the
      mutation in the BRCA1 gene and the presence of ovarian cancer in a family.
      CONCLUSIONS: Among women with breast cancer and a family history of the disease,
      the percentage with BRCA1 coding-region mutations is less than the 45 percent
      predicted by genetic-linkage analysis. These results suggest that even in a
      referral clinic specializing in screening women from high-risk families, the
      majority of tests for BRCA1 mutations will be negative and therefore
      uninformative.

PMID- 9145678
TI  - Differential contributions of BRCA1 and BRCA2 to early-onset breast cancer.
AB  - BACKGROUND: Germ-line mutations in the BRCA1 and BRCA2 genes predispose women to
      breast cancer. BRCA1 mutations are found in approximately 12 percent of women
      with breast cancer of early onset, and the specific mutation causing a deletion
      of adenine and guanine (185delAG), which is present in 1 percent of the Ashkenazi
      Jewish population, contributes to 21 percent of breast cancers among young Jewish
      women. The contribution of BRCA2 mutations to breast cancer of early onset is
      unknown. METHODS: Lymphocyte specimens from 73 women with breast cancer diagnosed
      by the age of 32 were studied for heterozygous mutations of BRCA2 by a
      complementary-DNA-based protein-truncation assay, followed by automated
      nucleotide sequencing. In addition, specimens from 39 Jewish women with breast
      cancer diagnosed by the age of 40 were tested for specific mutations by an allele
      specific polymerase chain reaction. RESULTS: Definite BRCA2 mutations were found
      in 2 of the 73 women with early-onset breast cancer (2.7 percent; 95 percent
      confidence interval, 0.4 to 9.6 percent), suggesting that BRCA2 is associated
      with fewer cases than BRCA1 (P=0.03). The specific BRCA2 mutation causing a
      deletion of thymine (6174delT), which is found in 1.3 percent of the Ashkenazi
      Jewish population, was observed in 1 of the 39 young Jewish women with breast
      cancer (2.6 percent; 95 percent confidence interval, 0.09 to 13.5 percent),
      indicating that it has a small role as a risk factor for early-onset breast
      cancer. Among young women with breast cancer, there are BRCA2 mutations that
      cause truncation of the extreme C terminus of the protein and that may be
      functionally silent, along with definite truncating mutations. CONCLUSIONS: Germ
      line mutations in BRCA2 contribute to fewer cases of breast cancer among young
      women than do mutations in BRCA1. Carriers of BRCA2 mutations may have a smaller
      increase in the risk of early-onset breast cancer.

PMID- 9145679
TI  - Diagnosis of pulmonary embolism with magnetic resonance angiography.
AB  - BACKGROUND: Diagnosing pulmonary embolism may be difficult, because there is no
      reliable noninvasive imaging method. We compared a new noninvasive method,
      gadolinium-enhanced pulmonary magnetic resonance angiography, with standard
      pulmonary angiography for diagnosing pulmonary embolism. METHODS: A total of 30
      consecutive patients with suspected pulmonary embolism underwent both standard
      pulmonary angiography and magnetic resonance angiography during the pulmonary
      arterial phase at the time of an intravenous bolus of gadolinium. All magnetic
      resonance images were reviewed for the presence or absence of pulmonary emboli by
      three independent reviewers who were unaware of the findings on standard
      angiograms. RESULTS: Pulmonary embolism was detected by standard pulmonary
      angiography in 8 of the 30 patients in whom pulmonary embolism was suspected. All
      5 lobar emboli and 16 of 17 segmental emboli identified on standard angiograms
      were also identified on magnetic resonance images. Two of the three reviewers
      reported one false positive magnetic resonance angiogram each. As compared with
      standard pulmonary angiography, the three sets of readings had sensitivities of
      100, 87, and 75 percent and specificities of 95, 100, and 95 percent,
      respectively. The interobserver correlation was good (k=0.57 to 0.83 for all
      vessels, 0.49 to 1.0 for main and lobar vessels, and 0.40 to 0.81 for segmental
      vessels). CONCLUSIONS: In this preliminary study, gadolinium-enhanced magnetic
      resonance angiography of the pulmonary arteries, as compared with conventional
      pulmonary angiography, had high sensitivity and specificity for the diagnosis of
      pulmonary embolism. This new technique shows promise as a noninvasive method of
      diagnosing pulmonary embolism without the need for ionizing radiation or
      iodinated contrast material.

PMID- 9145680
TI  - Images in clinical medicine. Liver abscess with septic pulmonary emboli.

PMID- 9145681
TI  - Atrial arrhythmias after cardiothoracic surgery.

PMID- 9145682
TI  - Clinical problem-solving. Where did good old clinical diagnosis go?

PMID- 9145683
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 15-1997. Respiratory distress and seizure in a neonate.

PMID- 9145685
TI  - Pulmonary embolism--new diagnostic approaches.

PMID- 9145684
TI  - BRCA genes--bookmaking, fortunetelling, and medical care.

PMID- 9145687
TI  - Report on the 4th International Symposium of Ocular Inflammation.

PMID- 9145688
TI  - Effects of non-steroidal antiallergic eyedrops on the complement-mediated
      histamine release from human cells.
AB  - Leukocytes from ten allergic patients (five allergic to dust-mites and five
      allergic to pollen) were treated with N-acetyl aspartyl glutamic acid (NAAGA)
      4.9%, disodium cromoglycate (DSCG) 2%, lodoxamide (LODO) 1%, and levocabastine
      (LEVO) 0.5% (concentrations representing the pharmaceutical eyedrop preparations)
      for 20 minutes. Degranulation was then induced with Complement (rHu5Ca).
      Histamine was measured in the supernatant with ELISA. LODO and LEVO were inactive
      in blocking histamine released from human cells, and paradoxical unexpected
      effects were found with these two agents. They both induced significant histamine
      release in almost 100% of the samples. DSCG was able to block histamine release
      in seven patients out of nine (ranging between 5 and 34%). NAAGA was the most
      active agent on human cells and was able to block basophil degranulation in nine
      patients out of nine (inhibition ranging between 4 and 66% of total histamine
      pool).

PMID- 9145689
TI  - Uveitogenic 28/30 kD and 43 kD polypeptides in pigment epithelial membranes of
      the retina.
AB  - The purpose of this study was the search for new intrinsic polypeptides of the
      retinal pigment epithelium (RPE) capable of evoking experimental uveitis. A
      membrane fraction was prepared from purified bovine RPE cells. The Triton X-100
      soluble protein fraction was separated into polypeptide fractions by preparative
      gel electrophoresis, and the pathogenicity of the main isolated polypeptides was
      investigated in Lewis rats. After immunization, two hitherto unknown pigment
      epithelial polypeptides with M(r) 28/30 kD (doublet) and 43 kD (PEP-28/30 and PEP
      43, respectively) elicited progressive pigment epitheliitis and choroiditis
      accompanied by extending plaque-shaped macrophage accumulations along the RPE
      Bruch's membrane layer. No inflammatory foci were found within the neural retina.
      Polypeptide fractions with M(r) 14-17, 25 and 32/34 kD (doublet) (PEP-14/17, PEP
      25 and PEP-32/34, respectively) appeared to be non-uveitogenic at the tested
      dose. PEP-28/30 and PEP-43 exhibited a partial antigenic relationship to PEP-65.
      PEP-28/30 exhibited marked reactivity to a monoclonal antibody previously raised
      to a 32 kD RPE-specific protein. IN CONCLUSION: in addition to the previously
      described main RPE-specific membrane polypeptide PEP-65, the RPE appears to
      contain two more uveitogenic components, the intrinsic pigment epithelial
      membrane polypeptides PEP-28/30 and PEP-43. Like PEP-65, these antigens are able
      to evoke experimental autoimmune pigment epithelial protein-induced uveitis
      (EAPU) in rats.

PMID- 9145690
TI  - Cataract extraction in Behcet's disease.
AB  - AIMS/BACKGROUND: To assess the outcome and complications of cataract extraction
      in patients with Behcet's disease. METHODS: Thirty-six Behcet's disease patients
      underwent cataract surgery without intraocular lens implantation. Twenty-six
      patients had phacoemulsification or extracapsular cataract extraction, and ten
      patients had pars plana lensectomy/vitrectomy. The follow-up period ranged from
      24 to 84 months (mean, 38 months). RESULTS: There was no statistically
      significant difference in the follow-up period of patients who underwent
      phacoemulsification, extracapsular cataract extraction, or pars plana
      lensectomy/vitrectomy. Sixteen (62%) of 26 patients who had extracapsular
      cataract extraction or phacoemulsification had a visual acuity of 20/200 or
      better compared with none of the 10 patients who had pars plana
      lensectomy/vitrectomy. Three (30%) of ten eyes which underwent pars plana
      lensectomy/vitrectomy eventuated in phthisis bulbi while none of the eyes that
      underwent extracapsular cataract extraction or phacoemulsification developed
      phthisis bulbi. CONCLUSION: Extracapsular cataract extraction or
      phacoemulsification had a better visual outcome and fewer postoperative
      complications than pars plana lensectomy/vitrectomy in patients with Behcet's
      disease.

PMID- 9145691
TI  - Influence of topical anesthesia on tests diagnostic of blepharitis-associated dry
      eye syndrome.
AB  - PURPOSE: Despite the high frequency and clinical relevance of blepharitis
      associated dry-eye syndrome, no agreement exists about whether diagnostic tests
      should be performed with or without topical anesthesia. The aim of this study was
      to compare the influence of topical anesthesia on the mean values of Schirmer's
      test, tear lysozyme, tear lactoferrin, and tear osmolarity in patients suffering
      from blepharitis-associated dry eye syndrome. METHODS: The authors compared the
      mean values of Schirmer's test, tear osmolarity, tear lysozyme (turbidimetric
      assay), and tear lactoferrin (radial immunodiffusion) before and after topical
      anesthesia in the following groups: 56 normal subjects (group 1), 62 blepharitis
      patients (group 2), and 15 patients with blepharitis-associated dry eye syndrome
      (group 3). All clinical and laboratory tests were performed by masked observers.
      RESULTS: In group I, mean values of Schirmer's test decreased 24.8% (p < 0.01)
      when performed after application of topical anesthesia. The other tests were not
      significantly modified. In groups 2 and 3, significant differences were seen in
      Schirmer's test (25.33% and 24.19% respectively, p < 0.001) and the lysozyme
      determination (14.00% and 13.22% respectively, p < 0.01). Differences between the
      normal subjects (group I) and the patient groups increased when the tests were
      performed after application of topical anesthesia reaching statistical
      significance in group 3 for all the tests. CONCLUSIONS: Performing diagnostic
      tests after topical anesthesia instillation could be useful in detecting dry eye
      associated with blepharitis.

PMID- 9145692
TI  - MHC class II positive retinal pigment epithelial (RPE) cells can function as
      antigen-presenting cells for microbial superantigen.
AB  - Retinal pigment epithelial (RPE) cells induced to express MHC class II (HLA-DR)
      by incubation with interferon gamma (IFN-gamma) were investigated for their
      ability to present a microbial superantigen to T lymphocytes. Superantigens bind
      to MHC class II antigens and appear to play a role in a number of infectious and
      autoimmune diseases through stimulation of large numbers of T cells. Primary
      cultures of human RPE cells treated with IFN-gamma for three days to induce HLA
      DR expression bound staphylococcal enterotoxin E (SEE) via HLA-DR and presented
      SEE to T cells as measured by proliferation of purified peripheral blood T cells
      and IL-2 synthesis by the Jurkat T cell line. Untreated RPE cells were
      essentially ineffective as superantigen presenting cells. These results suggest
      that MHC class II expressing RPE cells could contribute to immune and
      inflammatory activity in the eye by presenting superantigens to T lymphocytes.

PMID- 9145693
TI  - Ophthalmic fluorometholone-gentamicin versus ophthalmic betamethasone-gentamicin
      following cataract surgery.
AB  - A prospective, randomised, investigator-masked, parallel-group study was
      performed to compare fluorometholone-gentamicin eye drops and ointment with
      betamethasone-gentamicin eyedrops and ointment in the control of ocular
      inflammation after cataract surgery. Seventy patients (35 in each treatment
      group) of both sexes undergoing cataract-lens implant surgery for visually
      disabling cataract were enrolled in the study. The demographic and baseline
      parameters on day I, the day after surgery, were similar in the two study groups.
      After treatment, on day 3 and day 6 post-operatively, the reduction in cells in
      the anterior chamber and conjunctival hyperaemia were similar in the two study
      groups. Both treatments were equally well-tolerated. Ophthalmic fluorometholone
      gentamicin was as effective as ophthalmic betamethasone-gentamicin in the control
      of ocular inflammation after cataract surgery.

PMID- 9145694
TI  - Experimental, cancer-induced retinopathy.

PMID- 9145695
TI  - Chronic Propionibacterium acnes endophthalmitis as a cause of intermediate
      uveitis.
AB  - Although the pathogenesis in most cases of intermediate uveitis is unknown, a
      small minority of cases is associated with a variety of specific inflammatory
      etiologies: sarcoidosis; multiple sclerosis; Lyme disease; syphilis; ocular
      lymphoma; and as a rare manifestation of Behcet's disease and AIDS. A 61-year-old
      woman developed pars planitis after cataract surgery. A vitrectomy was performed
      after ten months when a white capsular plaque and an hypopyon developed.
      Propionibacterium acnes was isolated. The intermediate uveitis was not controlled
      until later removal of the intraocular lens and capsular remnants. Chronic
      propionibacterial endophthalmitis may be a cause of intermediate uveitis.

PMID- 9145697
TI  - The etiology of the presumed ocular histoplasmosis syndrome.

PMID- 9145696
TI  - Commentary on histoplasmosis.

PMID- 9145698
TI  - A piece of my mind. The delivery.

PMID- 9145699
TI  - Study shows mastectomy prevents breast cancer in high-risk women.

PMID- 9145700
TI  - Online support group helps patients live with, learn more about the rare skin
      cancer CTCL-MF.

PMID- 9145701
TI  - Interventional radiological treatments tested.

PMID- 9145702
TI  - Refugees and AIDS.

PMID- 9145703
TI  - From the Centers for Disease Control and Prevention. Outbreaks of pseudo
      infection with Cyclospora and Cryptosporidium--Florida and New York City, 1995.

PMID- 9145704
TI  - Oncology ASAP. Where to find reliable cancer information on the Internet.

PMID- 9145705
TI  - Underdiagnosis of depression in primary care: by accident or design?

PMID- 9145706
TI  - Underdiagnosis of depression in primary care: by accident or design?

PMID- 9145707
TI  - Adverse outcomes of underuse of beta-blockers in elderly patients.

PMID- 9145708
TI  - Adverse outcomes of underuse of beta-blockers in elderly patients.

PMID- 9145709
TI  - Adverse outcomes of underuse of beta-blockers in elderly patients.

PMID- 9145710
TI  - Adverse outcomes of underuse of beta-blockers in elderly patients.

PMID- 9145711
TI  - Adverse outcomes of underuse of beta-blockers in elderly patients.

PMID- 9145712
TI  - Adverse outcomes of underuse of beta-blockers in elderly patients.

PMID- 9145713
TI  - Adverse outcomes of underuse of beta-blockers in elderly patients.

PMID- 9145714
TI  - Long-term suppression of HIV-1 by hydroxyurea and didanosine.

PMID- 9145715
TI  - Clinically recognized dysplastic nevi. A central risk factor for cutaneous
      melanoma.
AB  - OBJECTIVE: To investigate the relationship of number and type of nevi to the
      development of melanoma. DESIGN: Case-control study. SETTING: Outpatient clinics
      in referral hospitals. PATIENTS: Cases were 716 consecutive patients with newly
      diagnosed melanoma identified at 2 melanoma centers between January 1, 1991, and
      December 31, 1992. Stratified random sampling of patients from outpatient clinics
      was used to identify 1014 participating controls of the same age, sex, race, and
      geographic distribution as the melanoma cases. All study subjects underwent an
      interview, a complete skin examination, photography of the most atypical nevi,
      and, if the patient was willing, a biopsy of the most atypical nevus. MAIN
      OUTCOME MEASURES: Number and type of nevi on the entire body were systematically
      reported. All diagnoses of clinically dysplastic nevi were confirmed by expert
      examiners. RESULTS: Risk for melanoma was strongly related to number of small
      nevi, large nondysplastic nevi, and clinically dysplastic nevi. In the absence of
      dysplastic nevi, increased numbers of small nevi were associated with an
      approximately 2-fold risk, and increased numbers of both small and large
      nondysplastic nevi were associated with a 4-fold risk. One clinically dysplastic
      nevus was associated with a 2-fold risk (95% confidence interval, 1.4-3.6), while
      10 or more conferred a 12-fold increased risk (95% confidence interval, 4.4-31).
      Congenital nevi were not associated with increased risk of melanoma. CONCLUSIONS:
      Although nondysplastic nevi confer a small risk, clinically dysplastic nevi
      confer substantial risk for melanoma. On the basis of nevus number and type,
      clinicians can identify a population at high risk of this epidemic cancer for
      screening and intervention.

PMID- 9145716
TI  - Combination of prostate-specific antigen, clinical stage, and Gleason score to
      predict pathological stage of localized prostate cancer. A multi-institutional
      update.
AB  - OBJECTIVE: To combine the clinical data from 3 academic institutions that serve
      as centers of excellence for the surgical treatment of clinically localized
      prostate cancer and develop a multi-institutional model combining serum prostate
      specific antigen (PSA) level, clinical stage, and Gleason score to predict
      pathological stage for men with clinically localized prostate cancer. DESIGN: In
      this update, we have combined clinical and pathological data for a group of 4133
      men treated by several surgeons from 3 major academic urologic centers within the
      United States. Multinomial log-linear regression was performed for the
      simultaneous prediction of organ-confined disease, isolated capsular penetration,
      seminal vesicle involvement, or pelvic lymph node involvement. Bootstrap
      estimates of the predicted probabilities were used to develop nomograms to
      predict pathological stage. Additional bootstrap analyses were then obtained to
      validate the performance of the nomograms. PATIENTS AND SETTINGS: A total of 4133
      men who had undergone radical retropubic prostatectomy for clinically localized
      prostate cancer at The Johns Hopkins Hospital (n=3116), Baylor College of
      Medicine (n=782), and the University of Michigan School of Medicine (n=235) were
      enrolled into this study. None of the patients had received preoperative hormonal
      or radiation therapy. OUTCOME MEASURES: Simultaneous prediction of organ-confined
      disease, isolated capsular penetration, seminal vesicle involvement, or pelvic
      lymph node involvement using updated nomograms. RESULTS: Prostate-specific
      antigen level, TNM clinical stage, and Gleason score contributed significantly to
      the prediction of pathological stage (P<.001). Bootstrap estimates of the median
      and 95% confidence interval of the predicted probabilities are presented in the
      nomograms. For most cells in the nomograms, there is a greater than 25%
      probability of qualifying for more than one of the pathological stages. In the
      validation analyses, 72.4% of the time the nomograms correctly predicted the
      probability of a pathological stage to within 10% (organ-confined disease, 67.3%;
      isolated capsular penetration, 59.6%; seminal vesicle involvement, 79.6%; pelvic
      lymph node involvement, 82.9%). CONCLUSIONS: The data represent a multi
      institutional modeling and validation of the clinical utility of combining PSA
      level measurement, clinical stage, and Gleason score to predict pathological
      stage for a group of men with localized prostate cancer. Clinicians can use these
      nomograms when counseling individual patients regarding the probability of their
      tumor being a specific pathological stage; this will enable patients and
      physicians to make more informed treatment decisions based on the probability of
      a pathological stage, as well as risk tolerance and the values they place on
      various potential outcomes.

PMID- 9145717
TI  - Prostate cancer detection in men with serum PSA concentrations of 2.6 to 4.0
      ng/mL and benign prostate examination. Enhancement of specificity with free PSA
      measurements.
AB  - OBJECTIVE: To determine the detection rate of prostate cancer in a screening
      population of men with prostate-specific antigen (PSA) concentrations of 2.6 to
      4.0 ng/mL and a benign prostate examination, to assess the clinicopathological
      features of the cancers detected, and to assess the usefulness of measuring the
      ratio of free to total PSA to reduce the number of prostatic biopsies. DESIGN: A
      community-based study of serial screening for prostate cancer with serum PSA
      measurements and prostate examinations. SETTING: University medical center.
      SUBJECTS: A total of 914 consecutive screening volunteers aged 50 years or older
      with serum PSA levels of 2.6 to 4.0 ng/mL who had a benign prostate examination
      and no prior screening tests suspicious for prostate cancer, 332 (36%) of whom
      underwent biopsy of the prostate. MAIN OUTCOME MEASURES: Cancer detection rate,
      clinical and pathological features of cancers detected, and specificity for
      cancer detection using measurements of percentage of free PSA. RESULTS: Cancer
      was detected in 22% (73/332) of men who underwent biopsy. All cancers detected
      were clinically localized, and 81% (42/52) that were surgically staged were
      pathologically organ confined. Ten percent of the cancers were clinically low
      volume and low-grade tumors, and 17% of those surgically staged were low-volume
      and low-grade or moderately low-grade tumors (possibly harmless). Using a
      percentage of free PSA cutoff of 27% or less as a criterion for performing
      prostatic biopsy would have detected 90% of cancers, avoided 18% of benign
      biopsies, and yielded a positive predictive value of 24% in men who underwent
      biopsy. CONCLUSIONS: There is an appreciable rate of detectable prostate cancer
      in men with serum PSA levels of 2.6 to 4.0 ng/mL. The great majority of cancers
      detected have the features of medically important tumors. Free serum PSA
      measurements may reduce the number of additional biopsies required by the lower
      PSA cutoff.

PMID- 9145718
TI  - Recommended prostate-specific antigen testing intervals for the detection of
      curable prostate cancer.
AB  - OBJECTIVE: To evaluate prostate-specific antigen (PSA) testing intervals that
      maintain the detection of curable cancer and reduce unnecessary testing. DESIGN
      AND PATIENTS: Historical prospective study of serial PSA measurements at 2- and 4
      year intervals from frozen serum samples of 40 men who eventually developed
      prostate cancer and 272 men without prostate cancer who were participants in a
      prospective aging study (Gerontology Research Center of the National Institute on
      Aging, the Baltimore Longitudinal Study of Aging) and the case series of 389
      consecutive men treated surgically for nonpalpable prostate cancer. MAIN OUTCOME
      MEASURES: Probability of a PSA conversion to 4.1 to 5.0 ng/mL and to greater than
      5.0 ng/mL at 2 and 4 years and probability of detecting curable prostate cancer
      by age and PSA level. RESULTS: When the pretreatment PSA level was less than or
      equal to 4.0 ng/mL, nonpalpable prostate cancers were highly likely (34/36, 94%)
      to be curable (organ-confined or capsular penetration with Gleason score < 7 and
      negative margins), and the majority (25/36, 69%) were small cancers (confined
      tumor < or = 0.5 cm3 with no Gleason pattern 4 or 5). When the pretreatment PSA
      level was greater than 4.0 ng/mL and less than or equal to 5.0 ng/mL, cancers
      were highly likely to be curable (32/36, 89%), and a minority were small cancers
      (12/36, 33%). When the pretreatment PSA level was greater than 5.0 ng/mL, 96
      (30%) of 317 cancers were noncurable. The PSA conversion (for cancer cases) to a
      level at which cure is less likely (> 5.0 ng/mL) is rare (0%) after 2 or 4 years
      when the initial PSA is less than 2.0 ng/mL. PSA conversion to a range at which
      cancers are likely to be curable and less likely to be small (4.1-5.0 ng/mL) is
      rare after 2 years (0%-4%) when the baseline PSA level is less than 2.0 ng/mL but
      common when the baseline PSA level is between 2.1 and 3.0 ng/mL (27%) or 3.1 and
      4.0 ng/mL (36%). CONCLUSIONS: These data suggest that for men with no cancer
      suspected on digital rectal examination, a PSA level of 4.0 to 5.0 ng/mL is an
      acceptable range for maintaining the detection of curable prostate cancer and a 2
      year PSA testing interval is not likely to miss a curable prostate cancer when
      the initial PSA level is less than 2.0 ng/mL. Recognizing that 70% of a screened
      population between the ages of 50 years and 70 years have PSA levels less than
      2.0 ng/mL, elimination of annual PSA testing for these men would result in large
      health care cost savings.

PMID- 9145719
TI  - Endolymphatic sac tumors. A source of morbid hearing loss in von Hippel-Lindau
      disease.
AB  - OBJECTIVES: Isolated reports suggest a possible association of endolymphatic sac
      tumors (ELSTs), which are extremely rare in the general population, with von
      Hippel-Lindau disease (VHL). To determine if hearing loss and ELSTs are a
      component of VHL, we examined prevalence, clinical presentation, and natural
      history of hearing loss and ELSTs in VHL. DESIGN: Brain magnetic resonance images
      (MRIs) from 374 patients screened for VHL were reviewed for evidence of ELSTs.
      The VHL patients with MRI evidence suggestive of ELSTs or a history of hearing
      loss, tinnitus, or vertigo underwent additional radiologic and audiologic
      evaluations. To further assess prevalence of hearing loss and ELST in VHL, the
      next 66 patients screened in the VHL clinic (49 with proven VHL, 17 at risk for
      VHL) received MRI and audiologic assessment. SETTING: Referral center.
      PARTICIPANTS: Study subjects comprised 374 persons screened for VHL, 66
      consecutive patients with VHL or at risk for VHL, 4 patients with 6 ELSTs, and 13
      previously reported patients with VHL and invasive tumors of the temporal bone.
      INTERVENTION: Magnetic resonance image and computed tomographic (CT) scan of the
      posterior fossa and audiologic assessment. MAIN OUTCOME MEASURES: Any ELST
      visible on MRI or CT and hearing loss compatible with ELST. RESULTS: Magnetic
      resonance imaging revealed evidence of 15 ELSTs in 13 (11%) of 121 patients with
      VHL, but in none of the 253 patients without evidence of VHL (P<.001). Clinical
      findings in these 13 patients included hearing loss (13), tinnitus (12), vertigo
      (8), and facial paresis (1). Mean age at onset of hearing loss was 22 years
      (range, 12-50 years). Hearing for pure tones was abnormal in all affected ears
      and in 6 of the 11 additional, allegedly unaffected ears. In 8 patients (62%),
      hearing loss was the first manifestation of VHL. Presence or absence of hearing
      loss was associated with duration of symptoms (P<.002) and with tumor size
      (P<.01). Further, 43 (65%) of the 66 patients from the VHL clinic had pure tone
      threshold abnormalities, abnormalities that occurred bilaterally in 23 (54%) of
      the 43 affected subjects; however, evidence is lacking for a definitive
      association with ELST (3 [6%] of 49 patients with proven VHL had ELST evident on
      MRI). CONCLUSIONS: Hearing loss and ELSTs are frequently associated with VHL
      syndrome and should be considered when screening individuals at risk for VHL and
      when monitoring patients with an established diagnosis of VHL. Many patients with
      VHL have hearing loss without radiographic evidence of an ELST. Whether it is
      caused by an ELST that is too small to be detected by MRI or is produced by some
      other etiology is still unknown. Audiologic evaluation and MRI should allow early
      detection and enhance management of hearing loss in these patients.

PMID- 9145720
TI  - Genetic testing for susceptibility to adult-onset cancer. The process and content
      of informed consent.
AB  - OBJECTIVE: To provide guidance on informed consent to clinicians offering cancer
      susceptibility testing. PARTICIPANTS: The Task Force on Informed Consent is part
      of the Cancer Genetics Studies Consortium (CGSC), whose members were recipients
      of National Institutes of Health grants to assess the implications of cancer
      susceptibility testing. The 10 task force members represent a range of relevant
      backgrounds, including various medical specialties, social science, genetic
      counseling, and consumer advocacy. EVIDENCE: The CGSC held 3 public meetings from
      1994 to 1996. At its first meeting, the task force jointly established a list of
      topics. The cochairs (G.G. and J.R.B) then developed an outline and assigned each
      topic to an appropriate writer and reviewer. Writers summarized the literature on
      their topics and drafted recommendations, which were then revised by the
      reviewers. The cochairs compiled and edited the entire manuscript. All members
      were involved in writing this report. CONSENSUS PROCESS: The first draft was
      distributed to task force members, after which a meeting was held to discuss its
      content and organization. Consensus was reached by voting. A subsequent draft was
      presented to the entire CGSC at its third meeting, and comments were
      incorporated. CONCLUSIONS: The task force recommends that informed consent for
      cancer susceptibility testing be an ongoing process of education and counseling
      in which (1) providers elicit participant, family, and community values and
      disclose their own, (2) decision making is shared, (3) the style of information
      disclosure is individualized, and (4) specific content areas are discussed.

PMID- 9145721
TI  - Screening strategies for cancer. Implications and results.

PMID- 9145722
TI  - Genetics is coming to oncology.

PMID- 9145723
TI  - Information needs and decisional preferences in women with breast cancer.
AB  - OBJECTIVE: To determine the degree of involvement women with breast cancer wanted
      in medical decision making, extent to which they believed they had achieved their
      preferred level of involvement, and types of information they judged to be most
      important. DESIGN AND SETTING: Cross-sectional survey at 2 tertiary oncology
      referral clinics and 2 community hospital oncology clinics in Winnipeg, Manitoba.
      PATIENTS: Consecutive sample of 1012 women with a confirmed diagnosis of breast
      cancer who were scheduled for a visit at 1 of 4 hospital oncology clinics. MAIN
      OUTCOME MEASURES: The following measures were used: (1) Preferences about various
      levels of participation in treatment decision making; (2) the extent to which
      subjects believed they had achieved their preferred levels of involvement in
      decision making; and (3) priority needs for information and how these needs
      differed by selected sociodemographic, disease, and treatment variables. RESULTS:
      A total of 22% of women wanted to select their own cancer treatment, 44% wanted
      to select their treatment collaboratively with their physicians, and 34% wanted
      to delegate this responsibility to their physicians. Only 42% of women believed
      they had achieved their preferred level of control in decision making. The 2 most
      highly ranked types of information were related to knowing about chances of cure
      and spread of disease. Women younger than 50 years rated information about
      physical and sexual attractiveness as more important than did older women
      (P<.001); women older than 70 years rated information about self-care as more
      important than did younger women (P=.002); and women who had a positive family
      history of breast cancer rated information about family risk as more important
      than did other women (P=.03). CONCLUSIONS: The substantial discrepancy between
      women's preferred and attained levels of involvement in treatment decision making
      suggests that systematic approaches to assess and respond to women's desired
      level of participation in treatment decision making need to be evaluated.
      Priorities for information identified in this study provide an empirical basis to
      guide communication with women seeking care for breast cancer.

PMID- 9145724
TI  - Resistance to glycopeptides in enterococci.

PMID- 9145725
TI  - Botryomycosis.

PMID- 9145726
TI  - Wound infections following spinal fusion with posterior segmental spinal
      instrumentation.
AB  - Twenty-three of 238 patients (9.7%) developed wound infections following
      segmental spinal instrumentation. When the infected group and a matched control
      group were compared, the infected group had a significantly higher number of
      patients with cerebral palsy and myelodysplasia (nonambulatory), patients with
      wound hematomas, patients with fusions that extended into the sacral region, and
      patients who were incontinent of urine. A high incidence of infections with gram
      negative aerobic bacilli correlated with the extension of the surgery into the
      sacral region and bowel and/or bladder incontinence. Prophylactic antibiotics
      with broader coverage for gram-negative bacilli may be warranted for these
      procedures. Postoperative wound infections were managed by surgical drainage and
      debridement as well as antibiotics. Removal of the hardware was not necessary to
      control the infection in these patients who underwent segmental spinal
      instrumentation.

PMID- 9145727
TI  - Bacillary angiomatosis associated with myositis in a patient infected with human
      immunodeficiency virus.
AB  - A man with AIDS presented with a deep soft-tissue mass involving the right thigh.
      Biopsy of a skin lesion on the back and culture of a specimen from this lesion
      showed bacillary angiomatosis due to Bartonella (formerly Rochalimaea) quintana.
      Magnetic resonance imaging revealed a large heterogeneous mass involving the
      vastus medialis and intermedius muscles. Therapy with erythromycin caused rapid
      resolution of both the cutaneous lesion and the muscle lesion. Bartonella
      infection is proposed as an additional cause of bacterial myositis and expands
      the spectrum of presentation of bacillary angiomatosis.

PMID- 9145728
TI  - Human immunodeficiency virus infection is a major risk factor for detection of
      human papillomavirus DNA in esophageal brushings.
AB  - The presence of human papillomavirus (HPV) DNA in esophageal brushings from human
      immunodeficiency virus (HIV)-seropositive hosts was investigated in a cross
      sectional study. Oral and esophageal brushings from individuals scheduled for
      esophagogastroscopy (53 HIV-positive and 61 age-matched HIV-negative patients)
      were tested for the presence of HPV DNA by a consensus L1 polymerase chain
      reaction assay. HPV DNA was detected in esophageal brushings of 9 (17%) of the 53
      HIV-seropositive patients and 0 of the 61 HIV-negative individuals. HPV-16 DNA
      was the most frequently detected. No proliferative mucosal lesion was noted in
      individuals with HPV-positive esophageal brushings. Cytological smears were done
      for 6 of the 9 patients with HPV-positive esophageal brushings, and epithelial
      atypia was recorded for 1. HIV infection and a history of genital herpes were
      strong independent predictors of HPV, suggesting that HPV is transmitted sexually
      in the esophagus.

PMID- 9145729
TI  - Dosing of amoxicillin/clavulanate given every 12 hours is as effective as dosing
      every 8 hours for treatment of lower respiratory tract infection. Lower
      Respiratory Tract Infection Collaborative Study Group.
AB  - In this double-blind study, 557 patients with lower respiratory tract infection
      were randomly assigned to receive amoxicillin/clavulanate orally either every 12
      hours (875/125 mg) or every 8 hours (500/125 mg) for 7-15 days. For the 455
      patients evaluable for clinical efficacy at the end of therapy, clinical success
      was similar in the two groups: 93% and 94% in the 12-hour and 8-hour groups,
      respectively (P = .42). Bacteriologic success at the end of therapy was also
      comparable: 97% and 91% in the 12-hour and 8-hour groups, respectively (P = .86).
      The occurrence of adverse events related to treatment was similar for the two
      groups, but fewer patients in the 12-hour group reported moderate or severe
      diarrhea. Amoxicillin/clavulanate (875/125 mg) given every 12 hours is as
      effective and safe as every-8-hours administration of the combination (500/125
      mg) for the treatment of lower respiratory tract infection.

PMID- 9145730
TI  - Risk factors and attributable mortality associated with superinfections in
      neutropenic patients with cancer.
AB  - To identify the risk factors and attributable mortality associated with
      superinfections in febrile neutropenic patients with hematologic malignancies, we
      prospectively evaluated 333 episodes of fever and neutropenia by means of
      univariate and multivariate analyses. Superinfection was defined as any infection
      either occurring during antibiotic therapy or developing within 1 week after
      discontinuation of antibiotic therapy. Of 333 episodes, 46 (13.8%) were defined
      as superinfection; these episodes occurred in 46 patients. The risk factors for
      superinfection in the multivariate analysis were longer duration of profound
      neutropenia (P < .0001), lack of use of quinolones as prophylaxis (P < .0001),
      presence of a central venous catheter (P = .02), and persistence of fever after 3
      days of antibiotic therapy (P = .02). The crude mortality rate among patients
      with superinfection was 48%, and the attributable mortality rate was 24% (95%
      confidence interval, 3%-45%). Identifying risk factors for superinfections in
      neutropenic patients might allow clinical practices to reduce the negative impact
      of this complication.

PMID- 9145731
TI  - Primary cutaneous zygomycosis due to Saksenaea vasiformis and Apophysomyces
      elegans.
AB  - We report three cases of primary cutaneous zygomycosis due to either Saksenaea
      vasiformis (two patients) or Apophysomyces elegans (one patient). Extensive
      surgical debridement helped two patients recover from their infections. The
      underlying disease in the one patient who died was diabetes mellitus. We reviewed
      the literature on primary cutaneous zygomycosis and found that S. vasiformis and
      A. elegans were the etiologic agents in 16 and 13 earlier cases, respectively.

PMID- 9145732
TI  - The clinical significance of positive blood cultures in the 1990s: a prospective
      comprehensive evaluation of the microbiology, epidemiology, and outcome of
      bacteremia and fungemia in adults.
AB  - To assess changes since the mid-1970s, we reviewed 843 episodes of positive blood
      cultures in 707 patients with septicemia. The five most common pathogens were
      Staphylococcus aureus, Escherichia coli, coagulase-negative staphylococci (CNS),
      Klebsiella pneumoniae, and Enterococcus species. Although CNS were isolated most
      often, only 12.4% were clinically significant. Half of all episodes were
      nosocomial, and a quarter had no recognized source. Leading identifiable sources
      included intravenous catheters, the respiratory and genitourinary tracts, and
      intraabdominal foci. Septicemia-associated mortality was 17.5%. Patients who
      received appropriate antimicrobial therapy throughout the course of infection had
      the lowest mortality (13.3%). Multivariate analysis showed that age (relative
      risk [RR], 1.80), microorganism (RR, 2.27), source of infection (RR, 2.86),
      predisposing factors (RR, 1.98), blood pressure (RR, 2.29), body temperature (RR,
      2.04), and therapy (RR, 2.72) independently influenced outcome. Bloodstream
      infections in the 1990s are notable for the increased importance of CNS as both
      contaminants and pathogens, the proportionate increase in fungi and decrease in
      anaerobes as pathogens, the emergence of Mycobacterium avium complex as an
      important cause of bacteremia in patients with advanced human immunodeficiency
      virus infection, and the reduction in mortality associated with infection.

PMID- 9145733
TI  - Varicella-zoster virus is strongly associated with atypical necrotizing herpetic
      retinopathies.
AB  - Aqueous humor samples from nine patients with atypical necrotizing retinopathies
      of suspected viral origin, six with acute retinal necrosis syndrome (ARN), and 17
      with active cytomegalovirus (CMV) retinitis underwent amplification for viral DNA
      of herpes simplex virus type 1 (HSV-1), varicella-zoster virus (VZV), and human
      CMV. VZV DNA was detected in seven of the nine aqueous humor samples from
      patients with atypical necrotizing retinopathies of suspected viral origin and in
      four of the six samples from individuals with ARN; of the two other samples from
      patients with ARNS, no viral DNA was found in one, and both CMV DNA and HSV-1
      DNA, but not VZV DNA, were detected in one (this patient presented with bilateral
      ARNS 2 months after being successfully treated for CMV retinitis). Thus, VZV is
      likely to be the main pathogen of atypical necrotizing herpetic retinopathies.
      DNA amplification may be used to establish an early, sensitive, and reliable
      diagnosis of any form of necrotizing retinopathy in 80% of cases, irrespective of
      viral etiology.

PMID- 9145734
TI  - Current practices of preoperative bowel preparation among North American
      colorectal surgeons.
AB  - In North America, the rate of infections following colorectal surgery decreased
      after the introduction of oral antibiotic bowel preparation against colonic
      microflora. Eight hundred eight board-certified colorectal surgeons were surveyed
      for their current bowel preparation practices before elective procedures. The 471
      responders (58%) all use mechanical preparation: oral polyethylene glycol
      solution (70.9% of the respondents), oral sodium phosphate solution with or
      without bisacodyl (28.4%), and "traditional" methods of dietary restriction,
      cathartics, and enemas (28.4%). Most surgeons (86.5%) add oral and parenteral
      antibiotics to the regimen; 11.5% add only parenteral antibiotics, 1.1% add only
      oral antibiotics, and 0.9% add no antibiotics. Generally (77.8% of cases), oral
      neomycin and erythromycin or metronidazole are combined with a perioperative
      parenteral antibiotic. Most individuals start the preparation as outpatients the
      day before surgery, and the parenteral drugs are added to the regimen 1-2 hours
      before the procedure. The use of outpatient bowel preparation is increasing;
      however, patient selection is critical, and education is needed to reduce the
      rate of complications.

PMID- 9145735
TI  - Cytomegalovirus retinitis: decreased risk of bilaterality with increased use of
      systemic treatment. Swiss HIV Cohort Study Group.
AB  - Cytomegalovirus (CMV) retinitis may be treated systemically or intravitreally. We
      reviewed retrospectively patients with CMV retinitis, in order to determine
      whether systemic treatment was associated with less spread of CMV retinitis from
      one eye to the other. Of 222 cases, 92 patients had bilateral disease at onset of
      CMV retinitis, leaving 130 for analysis. Bilaterality occurred in 10 patients
      during 12,687 days of systemic treatment and in 34 during 14,791 days without
      systemic treatment (odds ratio [OR] = 2.92; confidence interval [CI], 1.44-5.90).
      Patients who had received systemic treatment for <50% of the follow-up period had
      a greater risk of bilaterality (OR = 3.7; CI, 2.79-4.54) than did the more
      intensively treated patients. CD4 cell levels also contributed to increased risk,
      but multivariate analysis showed that CD4 cell counts and treatment intensity
      were independent risk factors. CMV retinitis was more likely to become bilateral
      in patients who received less intravenous therapy. Local treatment can complete
      but does not replace systemically administered therapy.

PMID- 9145736
TI  - Toxoplasmosis in kidney transplant recipients: report of six cases and review.
AB  - Six patients with toxoplasmosis complicating renal transplantation are described,
      and 25 other reported cases are reviewed. The mean age of the 31 patients was
      35.16 years. Most of the recipients (25 of 29) showed signs of toxoplasmosis
      within 3 months post-transplantation, with fever, neurological disturbances, and
      pneumonia as the main clinical features. Diagnosis was established at autopsy in
      15 cases, by serology in 13 cases, and by direct examination, culture, or
      polymerase chain reaction of biological samples in 5 cases. Seventeen patients
      also had concomitant infections. The donor was the likely source of transmission
      to 10 recipients; reactivation was suspected in two cases. The source of
      transmission could not be determined for the remaining 19 patients. The mortality
      rate was 64.5%. Ten of the 11 patients given specific treatment survived,
      indicating that early diagnosis and therapy are essential.

PMID- 9145737
TI  - Amphotericin B colloidal dispersion vs. amphotericin B as therapy for invasive
      aspergillosis.
AB  - To assess the efficacy and safety of amphotericin B colloidal dispersion (ABCD),
      82 patients with proven or probable aspergillosis who were treated in clinical
      trials with ABCD were compared retrospectively with 261 patients with
      aspergillosis who were treated with amphotericin B at six cancer or transplant
      centers from January 1990 to June 1994. The groups were balanced in terms of
      underlying disease; ABCD recipients were younger and more likely to have
      preexisting renal insufficiency than were amphotericin B recipients (40.7% vs.
      8.7%, respectively), and amphotericin B recipients were more likely to be
      neutropenic at baseline than were ABCD recipients (42.5% vs. 15.9%,
      respectively). Response rates (48.8%) and survival rates (50%) among ABCD-treated
      patients were higher than those (23.4% and 28.4%, respectively) among
      amphotericin B-treated patients (P < .001 for both comparisons). Renal
      dysfunction developed less frequently in ABCD recipients than in amphotericin B
      recipients (8.2% vs. 43.1%, respectively; P < .001). Multivariate analysis
      revealed that treatment group was the best predictor of response, mortality, and
      nephrotoxicity (ABCD: relative risk [RR] = 3.00, P = .002; RR = 0.35, P < .001;
      and RR = 0.13, P = .001; respectively). This retrospective study suggests that in
      the treatment of aspergillosis ABCD causes fewer nephrotoxic effects than
      amphotericin B and the efficacy of ABCD is at least comparable with that of
      amphotericin B.

PMID- 9145738
TI  - Antibiotic therapy for diabetic foot infections: comparison of two parenteral-to
      oral regimens.
AB  - This prospective, randomized, multicenter trial compared the efficacy of two
      antibiotic regimens for treatment of foot infections in diabetic adults. Patients
      with infections requiring hospitalization were randomized to receive either
      intravenous ofloxacin followed by oral ofloxacin or intravenous
      ampicillin/sulbactam followed by oral amoxicillin/clavulanate (the
      aminopenicillin regimen) for 14-28 days. Patients with osteomyelitis were
      eligible for the study if the infected bone was to be removed. Of 108 patients
      enrolled in the study, 88 who were evaluable had various skin and soft-tissue
      infections, and 24% had osteomyelitis. For the ofloxacin and aminopenicillin
      regimens, the mean duration of intravenous therapy was 7.8 and 7.1 days,
      respectively, the mean duration of oral therapy was 13.2 and 12.0 days,
      respectively, the rate of eradication of pathogens was 78% and 88%, respectively,
      and the overall rate of clinical cure or improvement was 85% and 83%,
      respectively. Thus, about 3 weeks of therapy with either regimen was well
      tolerated and effective in treating these diabetic foot infections.

PMID- 9145739
TI  - Treatment of Torulopsis glabrata vaginitis: retrospective review of boric acid
      therapy.
AB  - The charts of all patients who were seen at a vaginitis clinic between January
      1989 and December 1994 were retrospectively reviewed; 80 patients whose vaginal
      cultures yielded Torulopsis glabrata were identified. Sixty of these patients
      experienced 75 symptomatic episodes of vaginitis attributed to T. glabrata, and
      these patients are the subject of this review. Of the 60 symptomatic patients, 40
      had uncomplicated T. glabrata infection, and 20 had mixed infection, most
      commonly in association with bacterial vaginosis. Evaluation of treatment of T.
      glabrata vaginitis with vaginal boric acid (600 mg/d for 14 days) revealed
      clinical improvement or cure in 21 (81%) of 26 episodes and mycological
      eradication in 20 (77%) of 26 episodes. One-third of the patients received
      maintenance therapy with boric acid. The clinical response and mycological
      eradication rates associated with therapy with topical and systemic azoles were
      <50%. The rate of therapeutic response to boric acid administered to patients
      with mixed T. glabrata infection remained high. In conclusion, in this series of
      patients with T. glabrata vaginitis, for whom repeated courses of antimycotic
      therapy with azoles had previously failed, boric acid emerged as a promising
      modality of therapy.

PMID- 9145740
TI  - Association of antibodies to Chlamydia trachomatis heat-shock protein 60 kD with
      chronic nongonococcal urethritis.
AB  - Ninety male patients with acute nongonococcal urethritis (NGU) who presented for
      follow-up 10-92 days after initiation of treatment were evaluated. A polymerase
      chain reaction assay and direct fluorescence antibody test were used to detect
      Chlamydia trachomatis at presentation and during follow-up. Chlamydial heat-shock
      protein 60 kD (hsp60) serology with an enzyme-linked immunosorbent assay and C.
      trachomatis serology with a microimmunofluoresence test were undertaken. In 62
      (69%) of the men, evidence of chronic urethritis was noted during follow-up. C.
      trachomatis was detected in only two patients during follow-up. Chlamydial hsp60
      antibody was associated with the development of chronic urethritis between 10 and
      92 days after treatment began (P < .04), that is, at 10-29 days (P < .02) and at
      30-92 days (P < .008). These results are consistent with the theory that immune
      response to hsp60 is important in the development of this chronic disease. The
      results also suggest that chronic NGU is not a consequence of continued
      production of hsp60 by C. trachomatis.

PMID- 9145741
TI  - A prospective study of tuberculosis and human immunodeficiency virus infection:
      clinical manifestations and factors associated with survival.
AB  - We prospectively studied the effect of human immunodeficiency virus (HIV)
      infection on the presentation and outcome of tuberculosis. A total of 216
      patients with tuberculosis were identified; 162 (75%) of these patients were
      tested for antibodies to HIV; 92 (57%) were seropositive. The patients who were
      seropositive for HIV were more likely to be male and Hispanic and to have been
      homeless or incarcerated. Eighty-one percent of these patients had CD4 lymphocyte
      counts of < or =200/mm3. The seropositive patients had extrapulmonary
      tuberculosis more often than did the seronegative patients (odds ratio [OR], 2.3;
      95% confidence interval [CI], 1.2-4.8). Smears for acid-fast bacilli were
      positive more often for non-HIV-infected patients with pulmonary tuberculosis
      (74.5%) than for HIV-infected patients (54.3%) [OR, 2.46; 95% CI, 1.01-6.02]-even
      those with focal or cavitary disease. A delay in initiating therapy was
      associated with in-hospital mortality: the median time from admission to the
      start of treatment was 4 days for patients who survived and 15 days for those who
      died (P = .02). The median survival was 22.7 months for HIV-infected patients who
      did not die during the initial hospitalization. Factors independently associated
      with reduced rates of survival included the severity of immunodeficiency, nonuse
      of directly observed therapy, infection due to drug-resistant Mycobacterium
      tuberculosis, and a history of injection drug use.

PMID- 9145742
TI  - Infective endocarditis: 35 years of experience at a children's hospital.
AB  - We review the predisposing conditions, the presenting signs and symptoms, as well
      as the risk factors and bacterial etiologies in children with infective
      endocarditis, focusing on hospital course and outcome. We conducted a
      retrospective analysis of 76 cases of endocarditis in 73 patients occurring at
      Children's Hospital of Pittsburgh from January 1958 through December 1992. The
      median age of the patients was 9 years (range, 1 month to 18 years). Predisposing
      conditions included congenital heart disease (62 patients) and rheumatic heart
      disease (four patients). Seventy-seven percent of the children with congenital
      heart disease had undergone cardiac surgery. After therapy with appropriate
      antibiotics was started, blood cultures for 67 patients (70 episodes of infective
      endocarditis) remained positive for a mean (+/-SD) of 0.7 +/- 1.41 days, and all
      patients who presented with fever (75 episodes in 72 patients) remained febrile
      for a mean (+/-SD) of 4.28 +/- 6.21 days. Secondary fever occurred in 39% of the
      children. Thirty (41%) of the 73 patients survived without any complications and
      13 (18%) died. Fifteen children with complications required surgery. Children
      with endocarditis caused by Staphylococcus aureus were more likely than those
      with infection caused by viridans streptococci to have prolonged fever, secondary
      fever, and/or complications as well to require surgery.

PMID- 9145743
TI  - Toxoplasmic myocarditis and polymyositis in patients with acute acquired
      toxoplasmosis diagnosed during life.
AB  - The presence of both toxoplasmic myocarditis and myositis in the same individual
      has been reported only at autopsy. We report the first case of biopsy-proven
      toxoplasmic myocarditis and polymyositis simultaneously occurring in the same
      individual that was diagnosed during life. Results of her toxoplasmic serology
      were consistent with acute toxoplasmosis. She subsequently developed visual
      symptoms consistent with toxoplasmic chorioretinitis. She had a positive clinical
      response to therapeutic agents specific against Toxoplasma gondii. Her
      toxoplasmic serological profile established the diagnosis of acute toxoplasmosis.
      A toxoplasmic serological profile should be obtained for patients with
      myocarditis and/or polymyositis of unclear etiology. Endomyocardial or skeletal
      muscle tissue biopsies may establish the definitive diagnosis of toxoplasmic
      myocarditis or polymyositis, respectively. Examination of blood by polymerase
      chain reaction analysis before antitoxoplasmic treatment and early in the course
      of primary infection with T. gondii may prove useful.

PMID- 9145744
TI  - Human leishmaniasis: clinical, diagnostic, and chemotherapeutic developments in
      the last 10 years.
AB  - The current interest in leishmaniasis stems from the importance of this disease
      with respect to travel medicine, veterans of Operation Desert Storm, humanitarian
      concerns, and infection with human immunodeficiency virus. Herein, I review
      aspects of leishmaniasis that are of practical value to practitioners, including
      presentation, diagnosis, and chemotherapy; I will emphasize advances in
      chemotherapy over the last 10 years. Amphotericin B and its new lipid
      formulations are now competitive with pentavalent antimony as primary therapy for
      visceral leishmaniasis. Pentamidine, paromomycin, and adjunctive therapy with
      interferon-gamma are secondary regimens for the treatment of this condition. High
      dose long-term regimens of antimony have been shown to be highly effective for
      the treatment of cutaneous leishmaniasis. Preliminary evidence of efficacy has
      been observed with short courses of pentamidine for the treatment of Leishmania
      braziliensis complex disease and topical paromomycin/methylbenzethonium chloride
      for the treatment of Leishmania major disease.

PMID- 9145745
TI  - Skin colonization with vancomycin-resistant enterococci among hospitalized
      patients with bacteremia.
AB  - To assess the prevalence of skin and rectal colonization by vancomycin-resistant
      enterococci (VRE) in hospitalized bacteremic patients and to determine the
      relation between colonization and bacteremia, we compared 14 case patients who
      had bacteremia due to VRE with 30 control patients who had bacteremia due to
      other pathogens. Rectal colonization and skin (inguinal area and/or antecubital
      fossa) colonization with VRE were common among both case patients (100% had
      rectal colonization, and 86% had skin colonization) and control patients (37% had
      rectal colonization and 23% had skin colonization). Among patients with rectal
      colonization, skin colonization was more common when diarrhea or fecal
      incontinence was present. The bloodstream cleared without appropriate
      antimicrobial therapy in nine of the 14 patients with bacteremia due to VRE. The
      high prevalence of skin colonization with VRE may increase the risk of catheter
      related sepsis, cross-infection, or blood culture contamination (which may
      explain the frequent spontaneous resolution of bacteremia due to VRE).

PMID- 9145746
TI  - Acalculous nontyphoidal salmonellal cholecystitis requiring surgical intervention
      despite ciprofloxacin therapy: report of three cases.
AB  - Nontyphoidal salmonellal cholecystitis is a rare complication of nontyphoidal
      salmonellal enterocolitis. We describe three patients with this complication who
      were hospitalized in a regional infectious disease unit at Ruchill Hospital,
      Glasgow, Scotland, over a period of 12 months. All three patients were receiving
      ciprofloxacin therapy before the episodes of cholecystitis became clinically
      evident, and all required surgical intervention.

PMID- 9145747
TI  - Streptococcus suis infection complicated by purpura fulminans and rhabdomyolysis:
      case report and review.
AB  - Streptococcus suis infection, an important zoonotic occupational disease in
      humans, is associated with meningitis, arthritis, and perceptive deafness. We
      report a case of severe S. suis infection in a previously healthy man who
      developed purpura fulminans and rhabdomyolysis, complications not previously
      reported with this disease.

PMID- 9145748
TI  - Endophthalmitis due to Microbacterium species: case report and review of
      microbacterium infections.
AB  - Microbacterium species (formerly CDC [Centers for Disease Control and Prevention]
      coryneform group A-4 and A-5 bacteria) are widely distributed in the environment
      and rarely cause infections in humans. We present a case of endophthalmitis due
      to Microbacterium species that occurred after accidental trauma and review the
      literature on microbacterium infections. If the infected tissue or medical device
      is removed and antimicrobial therapy (preferably with beta-lactams or
      glycopeptides) is instituted, the prognosis is usually favorable for patients
      with microbacterium infections.

PMID- 9145749
TI  - Treatment of Bolivian hemorrhagic fever with intravenous ribavirin.
AB  - Bolivian hemorrhagic fever (BHF) is a potentially severe febrile illness caused
      by Machupo virus (family Arenaviridae). Initial symptoms include headache, fever,
      arthralgia, and myalgia. In the later stages of this illness, patients may
      develop hemorrhagic manifestations including subconjunctival hemorrhage,
      epistaxis, hematemesis, melena, and hematuria, as well as neurological signs
      including tremor, seizures, and coma. During the BHF epidemics of the 1960s,
      convalescent-phase immune plasma from survivors of BHF was administered to
      selected patients infected with Machupo virus. However, there is currently a
      paucity of survivors of BHF who can donate immune plasma, and there is no active
      program for collection and storage of BHF immune plasma; therefore, we had the
      opportunity to offer intravenous ribavirin to two of three patients with this
      potentially life-threatening infection. One patient with laboratory-confirmed
      Machupo virus infection who received ribavirin recovered without sequelae, as did
      a second patient with suspected BHF whose epidemiological and clinical features
      were similar to those of the first patient. This report describes the first use
      of intravenous ribavirin therapy for BHF in humans, and the results suggest the
      need for more extensive clinical studies to assess the usefulness of ribavirin
      for treating BHF.

PMID- 9145750
TI  - Chronic invasive aspergillosis in apparently immunocompetent hosts.
AB  - Seventeen cases of invasive aspergillosis occurring since 1987 in apparently
      immunologically normal hosts have been reviewed: 9 of invasive sinus
      aspergillosis, 2 of isolated brain abscesses, 3 of pneumonia (1 in a patient who
      developed mediastinitis), 2 of lymph node aspergillosis, and 1 of osteomyelitis
      of the foot. Two of the 9 patients with sinus aspergillosis died; the rest were
      stable up to March 1993. They responded initially to combined surgical and
      medical therapy. Both patients with brain abscesses survived following surgery,
      but one had neurological sequelae. Both patients with pneumonia were well
      following therapy with amphotericin B; one also received itraconazole. The
      patient with mediastinitis died, but this disease was diagnosed late. The
      patients with lymph node involvement were lost to follow-up, as was the patient
      with osteomyelitis. Invasive aspergillosis may be common in Pakistan. Greater
      awareness would allow earlier diagnosis and therapy, thereby improving the
      outcome.

PMID- 9145751
TI  - Paradoxical subcutaneous tuberculous abscess.

PMID- 9145752
TI  - Intrabronchial pseudallescheriasis in an immunocompetent woman.

PMID- 9145753
TI  - Use of the polymerase chain reaction for demonstration of influenza virus
      dissemination in children.

PMID- 9145754
TI  - Outbreak of tetanus among elderly women treated with sheep cell therapy.

PMID- 9145755
TI  - Septicemia caused by Neisseria weaveri.

PMID- 9145756
TI  - Ocular infection caused by three unusual marine organisms.

PMID- 9145757
TI  - Recrudescence of initial cutaneous lesions after crusting of chickenpox in an
      adult with advanced AIDS suggests prolonged local viral persistence.

PMID- 9145758
TI  - Chemotherapy for tuberculous meningitis in adults.

PMID- 9145759
TI  - Intraluminal antibiotic treatment of central venous catheter infections in
      patients receiving parenteral nutrition at home.

PMID- 9145760
TI  - Clinical and environmental factors associated with cryptococcosis in liver
      transplant recipients.

PMID- 9145762
TI  - Ocular toxoplasmosis as the presenting manifestation of human immunodeficiency
      virus infection.

PMID- 9145763
TI  - Effects of antidepressants on phencyclidine-induced enhancement of immobility in
      a forced swimming test in mice.
AB  - We have previously found that repeated phencyclidine (PCP) treatment enhances the
      immobility induced by forced swimming and suggested that this behavioral change
      could be used as a model of the negative symptoms, particularly depression, of
      schizophrenia. The present study attempted to examine the effects of
      antidepressants on the depressive states (immobility) induced by forced swimming
      in mice repeatedly treated with PCP, compared with those in mice repeatedly
      treated with saline. In mice repeatedly treated with saline, desipramine (5 and
      10 mg/kg) and imipramine (5 and 10 mg/kg) significantly attenuated immobility,
      whereas mianserin (5-20 mg/kg) and clomipramine (10 and 50 mg/kg) had no affect.
      In mice repeatedly treated with PCP, the enhancing effect of PCP on immobility
      was attenuated by mianserin (5-20 mg/kg) at doses which did not have any effect
      in saline-treated mice, and by desipramine at higher doses (20 and 50 mg/kg).
      However, imipramine (5-20 mg/kg) and clomipramine (10-50 mg/kg) did not affect
      PCP-induced enhancement of immobility. In the biochemical study, the content of 5
      hydroxyindoleacetic acid (5-HIAA) and the 5-HIAA/5-hydroxytryptamine (5-HT) ratio
      in the prefrontal cortex in mice repeatedly treated with PCP, but not with
      saline, following the forced swimming test were significantly increased, compared
      with those in the corresponding control mice (which did not perform the test).
      The present findings suggest that the depressive states induced by the forced
      swimming in mice repeatedly treated with PCP are less sensitive to acute
      treatment with tricyclic antidepressants, and this may be due to increase in 5-HT
      turnover. Antidepressants such as mianserin, which have the 5-HT2 receptor
      antagonist properties, may be useful for the treatment of negative symptoms of
      schizophrenia.

PMID- 9145764
TI  - Potent reinforcing effects of dihydroetorphine in rats.
AB  - Dihydroetorphine is a novel opioid that is an extremely potent analgesic in
      rodents. The reinforcing potency was determined in rats trained to self
      administer heroin and compared to those of fentanyl, heroin, 6-acetylmorphine and
      morphine for assessment of the abuse potential of dihydroetorphine using a
      procedure that determines the dose-effect curve in individual sessions.
      Dihydroetorphine produced a bimodal dose-effect curve similar to that of other
      opioids. Potency ratios were determined with morphine for the ascending and
      descending limbs of the dose-effect curve, as well as the dose that yielded
      maximal response rate. Fentanyl, heroin and 6-acetylmorphine were approximately
      100, 8 and 2 times more potent than morphine in maintaining self-administration,
      respectively. Dihydroetorphine was roughly 1500 to 3000 times more potent than
      morphine, however, depending upon the limb of the dose-effect curve used for
      comparison. These potency ratios of dihydroetorphine to morphine were somewhat
      less than has been reported for analgesia assays, and therefore this compound may
      have some clinical advantages over other opioids. However, these studies indicate
      significant abuse liability for dihydroetorphine given its potency in maintaining
      self-administration in these animals.

PMID- 9145765
TI  - Effects of the dopamine D3 receptor agonist, R(+)-7-hydroxy-N,N-di-n-propyl-2
      aminotetralin, on memory processes in mice.
AB  - The putative dopamine D3 receptor agonist, R(+)-7-hydroxy-N,N-di-n-propyl-2
      aminotetralin (R(+)-7-OH-DPAT) (0.1-100 microg/kg, s.c.), administered before
      training, immediately after training, and before retention significantly
      shortened step-down latency of passive avoidance learning, indicating the amnesic
      effects of R(+)-7-OH-DPAT. Neither the dopamine D1 receptor antagonist, R(+)-7
      chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzaz epine maleate
      R(+)-SCH23390) (2.5 and 5 microg/kg, i.p.), nor the dopamine D2 receptor
      antagonist, S(-)-sulpiride (10 and 30 mg/kg, i.p.), markedly influenced the R(+)
      7-OH-DPAT (10 and 100 microg/kg, s.c.)-induced amnesia. In addition, only a 1000
      microg/kg dose of R(+)-7-OH-DPAT decreased locomotor activity; 1 and 100
      microg/kg doses of the drug were ineffective. These results suggest that the
      amnesic effects of the dopamine D3 receptor agonist, R(+)-7-OH-DPAT, are not
      mediated via dopamine D1 or D2 receptors in the brain.

PMID- 9145766
TI  - The effect of novel anti-epileptic drugs in rat experimental models of acute and
      chronic pain.
AB  - The novel anti-epileptic drugs lamotrigine, felbamate and gabapentin were
      compared in rat experimental models of acute (tail flick) and chronic pain: the
      chronic constriction injury and spinal nerve ligation models. Lamotrigine (10-100
      mg/kg, s.c.), felbamate (150-600 mg/kg, i.p.) and gabapentin (30-300 mg/kg, i.p.)
      each reversed cold allodynia (chronic constriction injury model) with ED50 values
      of 28, 241 and 103 mg/kg, respectively, 1 h post-dose. However, only gabapentin
      reversed tactile allodynia (spinal nerve ligation model) with an ED50 of 34 mg/kg
      (i.p.). The established anti-epileptic drugs, carbamazepine (1-30 mg/kg, i.p.)
      and phenytoin (1-100 mg/kg, s.c.), were ineffective in both models. The anti
      allodynic effect of the newer anti-epileptic drugs was observed at doses that
      were either ineffective or produced only a negligible effect on acute nociceptive
      function and/or locomotor activity. In conclusion, the data suggest that the
      newer anti-epileptic drugs appear to have the potential to be effective
      alternatives to either carbamazepine or phenytoin in the treatment of neuropathic
      pain. However, only gabapentin ameliorated both cold and touch hyperesthesias.

PMID- 9145767
TI  - Pretreatment with 5-HT1A receptor agonist flesinoxan attenuates Fos protein in
      rat hypothalamus.
AB  - The 5-HT1A receptor agonist flesinoxan has anxiolytic activity and concurrently
      enhances plasma corticosterone levels in rats. After a second injection of
      flesinoxan 24 h later, the corticosterone response disappears, but not the
      anxiolytic effects. Male rats received two injections with either flesinoxan or
      vehicle within 24 h. Flesinoxan challenge enhanced Fos immunoreactivity in the
      paraventricular nucleus of the hypothalamus, the central amygdala, and the
      dorsolateral part of the bed nucleus of the stria terminalis and plasma
      corticosterone levels in the vehicle-pretreated rats. Flesinoxan pretreatment
      resulted in an attenuated response of plasma corticosterone levels and Fos
      positive neurons in the paraventricular nucleus of the hypothalamus, but not in
      the central amygdala and the bed nucleus after a flesinoxan challenge. The
      differential desensitization levels for both behaviour and neuroendocrine
      responses after flesinoxan treatment seem to correspond to different organization
      levels in the brain, like limbic system and hypothalamus.

PMID- 9145768
TI  - Excitatory amino acid receptor involvement in peripheral nociceptive transmission
      in rats.
AB  - The involvement of excitatory amino acid receptors in peripheral nociceptive
      processing was assessed in two separate experiments. In the first, one knee joint
      cavity of rats was injected with 0.1 ml of L-glutamate (0.001 mM; 0.1 mM; 1.0
      mM), L-aspartate (0.001 mM; 0.1 mM: 1.0 mM), L-arginine (0.1 mM) or different
      combinations of these amino acids. The animals tested for paw withdrawal latency
      to radiant heat and withdrawal threshold to von Frey filaments at different time
      points. Combinations of glutamate/aspartate, aspartate/arginine or
      glutamate/aspartate/arginine when injected into the joint, in the absence of any
      other treatment, reduced the paw withdrawal latency and withdrawal threshold
      immediately after the injection and persisting up to 5 h indicating the
      development of hyperalgesia and allodynia. Subsequent intra-articular injection
      of either an NMDA or a non-NMDA glutamate receptor antagonist ((+/-)-2-amino-7
      phosphonoheptanoic acid (AP7), 0.2 mM) or 6-cyano-7-nitroquinoxaline-2,3-dione
      (CNQX), 0.1 mM) attenuated the thermal hyperalgesia and the mechanical allodynia
      produced by glutamate/aspartate/arginine. On the other hand, in a second
      experiment intra-articular injection of AP7, ketamine or CNQX reversed the
      hyperalgesia and allodynia produced by injection of a mixture of kaolin and
      carrageenan into the joint. These receptor antagonists, however, did not have an
      effect on the joint edema. These findings provide evidence for a potential role
      of peripheral NMDA and non-NMDA receptors in nociceptive transmission.

PMID- 9145769
TI  - Methamphetamine-induced decrease in tryptophan hydroxylase activity: role of 5
      hydroxytryptaminergic transporters.
AB  - Methamphetamine-induced 5-hydroxytryptaminergic neuronal damage purportedly
      involves transport of newly released dopamine from extracellular spaces into 5
      hydroxytryptaminergic terminals. This hypothesis is based primarily on findings
      that dopamine is required for, whereas 5-hydroxytryptamine (5-HT) uptake
      inhibitors prevent, methamphetamine-induced deficits in 5-hydroxytryptaminergic
      neuronal function. This hypothesis is not, however, supported by findings
      presented in this study that 5-hydroxytryptaminergic neuronal damage, induced by
      p-chloroamphetamine, does not decrease [3H]dopamine uptake into rat brain
      synaptosomes prepared from 5-HT-transporter-containing tissue. Moreover, despite
      having greater affinity for the 5-HT transporter, citalopram has an IC50 for
      [1H]dopamine transport into these synaptosomal preparations that is considerably
      greater than that of fluoxetine. These data suggest that 5-HT transporters may
      not effect dopamine uptake and thereby methamphetamine-induced 5
      hydroxytryptaminergic neuronal damage. Other possible mechanisms related to 5-HT
      uptake inhibitor attenuation of methamphetamine-induced deficits were
      investigated. Fluoxetine pretreatment prevented the methamphetamine-induced
      decrease in tryptophan hydroxylase activity: this effect cannot be attributed to
      altered body temperatures or brain concentrations of methamphetamine which
      suggests that neither, per se, is sufficient to impair 5-hydroxytryptaminergic
      neuronal function.

PMID- 9145770
TI  - Examination of the effect of the cannabinoid receptor agonist, CP 55,940, on
      electrically evoked transmitter release from rat brain slices.
AB  - In the present study we examined the effect of the cannabinoid receptor agonist,
      [[1 a,2-(R)-5-(1,1-dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl)cyc lohexyl]
      phenol; CP 55,940] on [14C]acetylcholine and [3H]norepinephrine release from
      hippocampal slices and on [14C]acetylcholine release from striatal slices. CP
      55,940 potently inhibited electrically evoked [14C]acetylcholine release from
      hippocampal slices, with an EC50 of 0.02 microM and a maximal inhibition of 61%
      at 1 microM. The inhibition of acetylcholine release by CP 55,940 was partially
      antagonized (60%) by the cannabinoid receptor antagonist, [[N-piperidin-1-yl)-5
      (4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H-pyrazole-3-carboxamide
      hydrochloride; SR 141716A]. Alone, SR 141716A significantly enhanced stimulated
      [14C]acetylcholine release. In contrast to the effects of CP 55,940 on
      [14C]acetylcholine release, electrically evoked [3H]norepinephrine release from
      hippocampal slices and [14C]acetylcholine release from striatal slices were both
      unaffected by this compound. Similarly, hippocampal [3H]norepinephrine release
      and striatal [14C]acetylcholine release were not affected by SR 141716A. In
      conclusion, the results of this study extend our previous data indicating that
      cannabinoid receptors modulate acetylcholine release in the hippocampus. The
      effects of cannabinoid receptor activation on [3H]acetylcholine release in the
      hippocampus does not appear to extend to [3H]norepinephrine release from this
      region or to acetylcholine release from the striatum.

PMID- 9145771
TI  - The thromboxane A2 and K(ATP) channel antagonist actions of a series of
      sulphonylurea derivatives in the pig coronary artery.
AB  - The ability of a series of sulphonylurea derivatives to antagonise the
      vasorelaxant actions of the ATP-dependent K+ channel (K(ATP)) opener,
      levcromakalim, and the vasoconstrictor responses of the thromboxane A2 mimetic,
      U46619, were assessed in the pig coronary artery. The sulphonylurea derivatives
      of glibenclamide caused a rightward shift in the concentration-vasorelaxant
      response curve obtained to levcromakalim in arterial segments pre-constricted
      with acetylcholine (0.5 microM). From these shifts pK(B) were calculated to
      estimate the potency of these compounds as levcromakalim antagonists. Similarly
      U46619 concentration-vasoconstrictor responses curves were constructed in the
      absence and in the presence of a sulphonylurea derivative and pK(B) values
      calculated. Regression analysis of pK(B) values showed that there was a
      significant correlation between the potency of these compounds in the two systems
      studied indicating similar structure-activity relationships apply in both cases.
      That sulphonylureas regulate K(ATP) channel opening is well known and they do so
      through a specific receptor associated with the channel. The results obtained in
      this study may indicate that a sulphonylurea receptor may also be associated with
      thromboxane A2 excitation-contraction coupling.

PMID- 9145772
TI  - Venodilator effects of pranidipine, a 1,4-dihydropyridine Ca2+ channel
      antagonist, in rats: comparison with nifedipine and amlodipine.
AB  - The effects of pranidipine, a dihydropyridine Ca2+ channel antagonist, on mean
      circulatory filling pressure, an index of body venous tone, were compared with
      those of other dihydropyridines (nifedipine and amlodipine) and nitroglycerin in
      anaesthetized hexamethonium- and norepinephrine-treated rats. In this study, the
      compounds were used at doses having a equi-hypotensive effect. Intravenous bolus
      injection of pranidipine (10 and 30 microg/kg) significantly decreased mean
      circulatory filling pressure in a dose-dependent manner, as did nitroglycerin (30
      and 100 microg/kg). Nifedipine (30 and 100 microg/kg), however, did not affect
      mean circulatory filling pressure. Amlodipine (1000 and 3000 microg/kg) decreased
      mean circulatory filling pressure only at the higher dose. These results suggest
      that pranidipine has a greater venodilator effect than nifedipine and amlodipine.

PMID- 9145773
TI  - Regulation of protein kinases in steady-state contraction of cat gastric smooth
      muscle.
AB  - Cat gastric smooth muscle strips were used to investigate the involvement of
      protein kinases in the steady-state contraction induced by 1 microM acetylcholine
      or 20 mM KCI. The steady-state contraction induced by acetylcholine or KCl was
      inhibited by EGTA dose dependently. Voltage-dependent Ca2+ channel antagonists
      dose dependently inhibited the contractions induced by KCI as well as by
      acetylcholine. Inhibitory effects of voltage-dependent Ca2+ channel antagonists
      were significantly more prominent on KCI-induced contractions than on
      acetylcholine-induced contractions. The acetylcholine-induced contraction was
      dose dependently inhibited by 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate
      (TMB-8, a blocker of intracellular Ca2+ release), but the KCl-induced contraction
      was not inhibited at all. Therefore both intracellular Ca2+ release and
      extracellular Ca2+ influx seem to be necessary for the acetylcholine-induced
      contraction, but intracellular Ca2+ release is not necessary for the KCl-induced
      contraction. Protein kinase C inhibitors, 10 microM 1-(5-isoquinolinylsulfonyl)-2
      methyl-piperazine 2HCl (H-7) and 1 microM staurosporine, significantly inhibited
      the contraction induced by acetylcholine or KCl. Calmodulin antagonists, 30
      microM trifluoperazine and 50 microM N-(6-aminohexyl)-5-chloro-2
      naphthalenesulfonamide HCI (W-7), however, significantly inhibited the
      contraction induced by acetylcholine but not by KCl. A tyrosine kinase inhibitor,
      50 microM genistein, did not affect the acetylcholine-induced contraction but
      significantly inhibited the KCl-induced contraction. These results strongly
      suggest that the involvement of protein kinases in regulation of the steady-state
      contraction may be agonist-dependent.

PMID- 9145775
TI  - Contraction of human airway smooth muscle by endothelin-1 and IRL 1620: effect of
      bosentan.
AB  - We have examined whether 4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-2,2'-bipyrimidin-4
      yl]-benzen esulfonamide (bosentan; endothelin ET(A/B) receptor antagonist) and
      (R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]carbonyl] amino-4
      methylpentanoil]amino-3-[3-(1-methyl-1H-indoyl)]prop ionyl]amino-3-(2-pyridyl)
      propionic acid (FR 139317; endothelin ET(A) receptor antagonist) inhibit
      contractions of human airway smooth muscle induced by endothelin-1 or Suc
      [Glu9,Ala(11,15)]enthothelin-1-(8-21) (IRL 1620; endothelin ET(B) receptor
      agonist). Endothelin-1 and IRL 1620 were equipotent. Bosentan and FR 139317 (each
      10 microM) produced a small shift in response curves to endothelin-1 (1.6- and
      1.5-fold, respectively). However, bosentan was more potent against contractions
      elicited by IRL 1620 (10 microM, 11.2-fold shift) suggesting that these agonists
      exhibit different kinetic interactions with endothelin receptors or implying an
      interaction with a novel endothelin ET(B) receptor subtype in human airways.

PMID- 9145774
TI  - Fedotozine blocks hypersensitive visceral pain in conscious rats: action at
      peripheral kappa-opioid receptors.
AB  - The effect of fedotozine on visceral hypersensitivity was evaluated in conscious
      rats. One hour after colonic irritation (0.6% acetic acid intracolonically), a 30
      mmHg colonic distension was applied for 10 min. Irritation increased the number
      of abdominal contractions induced by colonic distension (23.4 +/- 4.1 versus 4.8
      +/- 1.4 in saline-treated rats, P < 0.001). Facilitation of colonic pain was
      reversed in a dose-dependent manner by fedotozine ((+)-(-1R1)-1-phenyl-1-[(3,4,5
      trimethoxy)benzyloxymethyl]-N ,N-dimethyl-n-propylamine), (+/-)-U-50,488H (trans
      (+/-)-3,4-dichloro-N-methyl-N-(2-1-pyrrolidinyl]cyclohexyl)benzen eacetamide) and
      morphine (respective ED50 values 0.67, 0.51 and 0.23 mg/kg s.c.). The kappa
      opioid receptor antagonist, nor-binaltorphimine, abolished the effects of
      fedotozine and (+/-)-U-50,488H but not those of morphine. Low doses of naloxone
      (30 microg/kg s.c.) blocked the effect of morphine but not of fedotozine or (+/-)
      U-50,488H. After intracerebroventricular administration, morphine was very potent
      (ED50 1.7 microg/rat), (+/-)-U-50,488H poorly active (58% of antinociception at
      300 microg/rat) and fedotozine inactive up to 300 microg/rat. These results show
      that fedotozine blocks hypersensitive visceral pain by acting on peripheral kappa
      opioid receptors in animals.

PMID- 9145776
TI  - Renal effects of a nitric oxide donor, NOC 7, in anesthetized rabbits.
AB  - Intrarenal arterial infusion of angiotensin II (4 ng/kg per min) reduced
      glomerular filtration rate and urinary Na+ excretion without affecting fractional
      Na+ excretion. Infusion of norepinephrine (30 ng/kg per min) reduced both urinary
      Na+ excretion and fractional Na+ excretion with a slight hypofiltration. The
      angiotensin II- and the norepinephrine-induced renal responses were suppressed
      during simultaneous infusion of a spontaneous nitric oxide donor 1-hydroxy-2-oxo
      3-(N-methyl-3-aminopropyl)-3-methyl 1-triazene (NOC 7, 30 ng/kg per min) which
      itself had little influence on the renal parameters. The results suggest that in
      the rabbit kidney in vivo NOC 7 can interfere with the angiotensin II-induced
      hypofiltration and norepinephrine-evoked tubular reabsorption and thereby
      suppresses their antinatriuretic actions.

PMID- 9145778
TI  - Antazoline increases insulin secretion and improves glucose tolerance in rats and
      dogs.
AB  - In vivo effects of an imidazoline devoid of alpha2-adrenoceptor antagonistic
      properties, antazoline, on insulin secretion and glycemia were investigated both
      in fasted rats and dogs. In both species, antazoline (1.5 mg/kg i.v.) transiently
      increased insulinemia without affecting basal plasma glucose levels. In contrast,
      during an i.v. glucose tolerance test, antazoline markedly potentiated insulin
      release and thus increased the glucose disappearance rate. In rats, during an
      oral glucose tolerance test, the intragastric administration of antazoline (1.5
      mg/kg) clearly enhanced insulin secretion and reduced hyperglycemia. In dogs
      provided with a venous pancreatico-duodenal bypass, antazoline (0.5 mg/kg i.v.)
      induced an immediate and transient increase in insulin and somatostatin but not
      in glucagon pancreatico-duodenal outputs. In conclusion, intravenously and orally
      administered, the imidazoline antazoline is able to stimulate insulin secretion
      in vivo and improve glucose tolerance. The imidazoline compounds could therefore
      have a potential therapeutic relevance as new antihyperglycemic insulinotropic
      agents.

PMID- 9145777
TI  - The effect of selective phosphodiesterase inhibitors on plasma insulin
      concentrations and insulin secretion in vitro in the rat.
AB  - We have examined in rats the effects of Org 9935 (4,5-dihydro-6-(5,6-dimethoxy
      benzo[b]-thien-2-yl)-methyl-1-(2H)-p yridazinone), a selective inhibitor of type
      3 phosphodiesterase (phosphodiesterase 3) and Org 30029 (N-hydroxy-5,6-dimethoxy
      benzo[b]-thiophene-2-carboximidamide HCl), an inhibitor of phosphodiesterase 3/4
      on rat plasma insulin and glucose concentrations in pentobarbitone-anaesthetised
      rats and on insulin secretion by rat isolated islets. We have also compared their
      effects on islet phosphodiesterase activity. Org 9935 (0.1 and 1.0 mg kg(-1) i.v.
      15 min previously) dose dependently elevated fasting and post-glucose (0.25 g kg(
      1) i.v.) plasma insulin concentrations. Org 30029 in a dose of 10 mg kg(-1), but
      not 1 mg kg(-1), also increased plasma insulin concentrations. Neither drug
      modified either fasting or post-glucose plasma glucose concentrations. Each drug
      augmented glucose-induced insulin release by rat isolated islets in a static
      incubation system, with approximate EC50 values of 1.5 microM for Org 9935 and 20
      microM for Org 30029. Phosphodiesterase activity, in both supernatant and pellet
      fractions of islet homogenates, was inhibited concentration dependently by each
      drug. Although the shape of the concentration-inhibition curve for Org 30029
      precluded estimation of an IC50 value, this drug was clearly much less potent
      than Org 9935 (IC50 about 50 nM) in inhibiting islet phosphodiesterase activity.
      We conclude that the increase in plasma insulin produced by each drug is a
      consequence of augmented insulin secretion, probably secondary to inhibition of
      phosphodiesterase 3 in the islet beta cell, with a resultant elevation in cAMP.
      The failure of the drugs to modify plasma glucose may be due to concomitant
      inhibition of cAMP phosphodiesterase in liver and adipose tissue.

PMID- 9145779
TI  - Specific and long-lasting suppression of rat adjuvant arthritis by low-dose
      Mycobacterium butyricum.
AB  - We have tested the therapeutic effect of intraperitoneal injections of
      Mycobacterium butyricum on the development of adjuvant arthritis in rats and we
      have explored the specificity and the duration of effectivity of this treatment.
      Rats with induced arthritis were injected intraperitoneally with the causative
      antigen, Mycobacterium butyricum, at concentrations 10 times lower than the
      inducing one, on the 3rd and 10th day after arthritis induction. The severity of
      the disease was assessed on the basis of physical (arthritis index, paw swelling)
      and biochemical (serum interleukin-6) parameters. The treatment with
      Mycobacterium butyricum led to a significant suppression of adjuvant-induced
      arthritis. This therapeutic effect was both antigen-specific, because
      intraperitoneal aspecific inflammation did not prevent the disease, and long
      lasting. The results obtained in this model confirm the possibility of modulating
      the autoimmune process even when the immunological response is already triggered,
      suggesting new therapeutic strategies, more suitable than preventive vaccination,
      in human autoimmune diseases.

PMID- 9145780
TI  - Role of the 5-HT receptor in neurogenic inflammation in Fisher 344 rat airways.
AB  - The increased plasma protein extravasation in the airways of Fisher 344 rats upon
      stimulation of sensory nerves is in part due to the degranulation of mast cells.
      In this study, we examined the role of 5-HT and histamine receptors in the
      capsaicin-induced increase in plasma protein extravasation in Fisher 344 rat
      airways, using Evans blue as an intravascular marker. We found that only 5-HT2
      receptor agonists increased baseline plasma protein extravasation. Furthermore,
      the 5-HT2 receptor antagonist ketanserin reduced the capsaicin-induced increase
      in plasma protein extravasation. Combining ketanserin with the tachykinin NK1
      receptor antagonist (+/-)-RP 67,580 ((3alphaR,7alphaR)-(7,7-diphenyl-2(1-imino-2
      (2-methoxyph enylethyl)-perhydraisoinositol-4-one))) abolished the neurogenic
      increase in plasma protein extravasation. Finally, using selective receptor
      agonists and antagonists, we demonstrated that there was no modulation of the
      capsaicin-induced rise in plasma protein extravasation by stimulation of either
      histamine receptors or 5-HT1, 5-HT3 and 5-HT4 receptors. We conclude that, in the
      airways of Fisher 344 rats, the neurogenic increase in plasma protein
      extravasation is caused by activation of both tachykinin NK1 receptors and 5-HT2
      receptors.

PMID- 9145781
TI  - Nifedipine, losartan and captopril effects on hyperplasia of vascular smooth
      muscle from Ren-2 transgenic rats.
AB  - Vascular smooth muscle cells from hypertensive transgenic rats for the mouse Ren
      2 gene exhibited radioimmunoassayable angiotensin II and hyperplasia in
      comparison with cells from Sprague-Dawley rats. However, neither captopril,
      losartan, saralasin, nor PD123319 (all at 10 microM) modified DNA synthesis or
      cell number observed in 4-day growth curves with 10% fetal calf serum. Nifedipine
      reduced DNA synthesis in both cell types, the concentration required being
      significantly higher in Sprague-Dawley- (1 microM) than in transgenic-derived
      cultures (100 nM). The EC50 values were of 2.43 +/- 0.32 and 1.0 +/- 0.17 microM,
      respectively (P < 0.05). In both cell types, only 10 microM nifedipine reduced
      serum-induced cell proliferation, but inhibition percentage was higher in
      transgenic-derived cultures. In conclusion, hyperplasia of transgenic-derived
      vascular smooth muscle cells is not blocked by angiotensin-converting enzyme
      inhibitors or angiotensin receptor antagonists, but these cells are more
      sensitive to the antiproliferative effects of nifedipine.

PMID- 9145782
TI  - Density-dependent proliferation of adult rat hepatocytes in primary culture
      induced by epidermal growth factor is potentiated by cAMP-elevating agents.
AB  - We investigated whether or not epidermal growth factor (EGF) and cAMP-elevating
      agents induce the proliferation of adult rat hepatocytes during the early (4 h
      after adding EGF) and late phases (21 h after adding EGF) of primary cultures.
      Adult rat hepatocytes did not significantly proliferate after culture with 20
      ng/ml EGF for 4 h at a density of 1 X 10(5) cells/cm2. In contrast, when the
      density was decreased by about one-third to 3.3 X 10(4) cells/cm2, the number of
      nuclei increased about 1.2-fold after culture with 10-20 ng/ml EGF for 4 h. Under
      these culture conditions, DNA synthesis began within 2-4 h of exposure to 20
      ng/ml of EGF, although at the high cell density, DNA was not synthesized during
      this period. The beta-adrenoceptor agonists, metaproterenol and isoproterenol,
      and other cAMP-elevating agents, such as glucagon, forskolin, and dibutyryl cAMP,
      potentiated both hepatocyte DNA synthesis and proliferation about 1.4-fold when
      cultured in combination with 20 ng/ml EGF. The stimulatory effects of
      metaproterenol and other cAMP-elevating agents were specifically blocked by the
      cAMP-dependent protein kinase inhibitor, H-89 (10(-7) M). The effect of EGF was
      almost completely suppressed by genistein (5 X 10(-6) M) and rapamycin (10
      ng/ml), but it was unaffected by wortmannin (10(-7) M). These results demonstrate
      that mature rat hepatocytes can proliferate very rapidly in low-density cultures
      with EGF, the effects of which were potentiated by beta-adrenoceptor agonists and
      cAMP-elevating agents. In addition, the activation of receptor tyrosine kinase
      and p70 ribosomal protein S6 kinase may be involved in EGF-induced hepatocyte DNA
      synthesis and proliferation.

PMID- 9145783
TI  - Activation of BK(Ca) channel via endothelin ET(A) receptors in porcine coronary
      artery smooth muscle cells.
AB  - It has been demonstrated previously that endothelin-1 stimulates the Ca2+
      activated K+ (BK(Ca)) channel activity in porcine coronary artery smooth muscle
      cells. The purpose of the present study was to delineate the endothelin receptor
      subtype involved in this action. In receptor binding studies, [125I]endothelin-1
      was shown to bind to the homogenate of porcine primary coronary artery smooth
      muscle cells in a single class of binding sites with K(D) and Bmax values of 73
      pM and 99 fmol/mg protein, respectively. Furthermore, endothelin-1 and endothelin
      3 displaced the binding of [125I]endothelin-1 to these cells with respective IC50
      values of 70 and 17000 pM, a 240-fold difference in potency. The effects of
      endothelin-3 on the activity of the BK(Ca) channel in porcine coronary artery
      smooth muscle cells were examined using the cell-attached patch-clamp technique.
      Similar to endothelin-1, endothelin-3 also exhibited a bell-shaped concentration
      response curve. A maximal increase of 95% in channel open-state probability (Po)
      was induced by 100 nM endothelin-3 as compared with the 320% increase in Po by 1
      nM endothelin-1. Thus, endothelin-1 was about 100-fold more potent and 3.4-fold
      more efficacious than endothelin-3 in this action. Both the receptor binding and
      the electrophysiological results suggest that the effects of endothelins on the
      BK(Ca) channel are mediated through the endothelin ET(A) receptor subtype.

PMID- 9145784
TI  - Tranilast inhibits the growth of rat mesangial cells.
AB  - We investigated the effects of tranilast on the growth of cultured rat mesangial
      cells. The number of mesangial cells increased fivefold during a 5-day incubation
      in RPMI 1640 with 20% fetal bovine serum. The number of cells was significantly
      lower in the presence of tranilast than in its abscence. Tranilast (0
      approximately 500 microM) inhibited platelet-derived growth factor (PDGF)-induced
      DNA synthesis of rat mesangial cells cultured in RPMI 1640 medium containing 0.5%
      fetal bovine serum in a dose-dependent manner. The inhibition of DNA synthesis by
      tranilast was not affected by the presence of indomethacin (1 microg/ml) or N(G)
      monomethyl-L-arginine (0.5 mM). Tranilast did not stimulate nitrite oxide
      synthesis in PDGF-stimulated cells. Mitogen-activated protein kinase activity in
      mesangial cells was significantly increased by exposure to PDGF, while the effect
      was significantly suppressed in the presence of tranilast. The present study
      revealed that tranilast inhibits the growth of rat mesangial cells, independently
      of nitric oxide or prostacycline synthesis.

PMID- 9145785
TI  - Inhibition by xipamide of amiloride-induced acidification in cultured rat
      cardiocytes.
AB  - The diuretic drug xipamide improves myocardial relaxation in hypertensive
      patients with left ventricular hypertrophy, but its mechanism of action is
      unknown. Here, xipamide was tested in cultured rat heart myogenic H9c2 cells and
      newborn cardiomyocytes for its effects on cell acidification (and Ca2+
      mobilization). In H9c2 cells, blocking Na+/H+ exchange with amiloride (2 mM)
      provoked cell acidification with rate = 0.82 +/- 0.17 pH units/h (n = 6).
      Xipamide 1 microM maximally inhibited 50 +/- 7% (n = 9) of cell acidification.
      The action of xipamide required the presence of HCO3- and was antagonized by the
      HCO3(-)-transport blocker DIDS (4,4'-diisothiocyanostilbene-2.2'-disulfonic
      acid). Conversely, the carbonic anhydrase (EC 4.2.1.1) inhibitor acetazolamide
      failed to prevent xipamide action. Finally, xipamide was without significant
      effect on the Ca2+ signals induced by endothelin-1, vasopressin or the Ca2+
      ionophore ionomycin. In newborn rat cardiomyocytes, xipamide reduced amiloride
      induced cell acidification at similar concentrations as in H9c2 cardiocytes, but
      with a slightly higher extent of maximal inhibition (70-80%). In conclusion,
      xipamide reduced amiloride-dependent cell acidification in the rat heart myogenic
      H9c2 cell line and in newborn rat cultured cardiomyocytes. This action of
      xipamide seems to be related to a complex interaction with DIDS-sensitive HCO3-
      movements. Prevention of cell acidification by xipamide could be involved in the
      beneficial effects of this compound in myocardial relaxation and left ventricle
      filling in hypertensive patients with left ventricular hypertrophy.

PMID- 9145786
TI  - Dual effects of extracellular ATP on the muscarinic acetylcholine receptor
      operated K+ current in guinea-pig atrial cells.
AB  - Adenosine 5'-triphosphate (ATP) is stored in sympathetic and parasympathetic
      nerve terminals and co-released with norepinephrine and acetylcholine during
      nerve stimulation. In the heart in situ parasympathetic nerve is tonically
      stimulated and the activated muscarinic acetylcholine-receptor-operated K+
      current (I(K,ACh)) plays an important role in the repolarization of the atrial
      action potential, the sinoatrial node automaticity and the atrioventricular
      conduction. In the present study, effects of extracellular ATP on the I(K,ACh)
      activated by carbachol or adenosine were examined in isolated guinea-pig atrial
      cells by use of the patch-clamp technique. ATP (10 microM) per se produced a
      transient activation of I(K,ACh) in atrial cells held at -40 mV. When I(K,ACh)
      was preactivated by 1 microM carbachol or 10 microM adenosine, ATP (1-100 microM)
      produced a transient increase followed by a sustained decrease of the current.
      These ATP-induced biphasic changes of I(K,ACh) were abolished by suramin (100
      microM) or reactive blue-2 (30 microM), but not by theophylline (500 microM),
      indicating the involvement of P2 purinoceptors. ATP also enhanced and then
      partially reversed the action potential shortening induced by carbachol or
      adenosine in current-clamped atrial cells. Extracellular ATP did not increase but
      decreased the openings of the single K(ACh) channel that were recorded by use of
      a pipette solution containing 1 microM carbachol in the cell-attached mode. Thus,
      P2 purinoceptor stimulation produces dual effects of ATP on the pre-activated
      I(K,ACh) and may modulate the chronotropic and inotropic responses during
      autonomic nerve stimulation.

PMID- 9145787
TI  - The mu-opioid receptor is necessary for [D-Pen2,D-Pen5]enkephalin-induced
      analgesia.
AB  - Interactions between delta-opioid receptors and morphine-preferring mu-opioid
      receptor subtypes have been suggested. Availability of transgenic mu-opioid
      receptor knockout mice allows assessment of mu-opioid receptor roles in the
      analgesia produced by the classical delta-opioid receptor agonist [D-Pen2,D
      Pen5]enkephalin (DPDPE) in hot-plate and tail-flick tests. DPDPE analgesia was
      dramatically reduced in mu-opioid receptor knockout mice in a gene-dose-dependent
      fashion. The analgesia induced by this classic delta-opioid receptor agonist
      depends on intact mu-opioid receptors, suggesting that selective delta-opioid
      receptor drugs may require mu-opioid receptor occupancies for full efficacy.

PMID- 9145788
TI  - Heterogeneity of cell firing properties and opioid sensitivity in the thalamic
      reticular nucleus.
AB  - The thalamic reticular nucleus receives afferents from the dorsal thalamus,
      cortex and brainstem, and projects back onto most cortically projecting thalamic
      nuclei thus playing a key role in the synchronization of the thalamocortical
      network. Although this nucleus was initially thought to consist of a homogeneous
      population of cells using GABA as a transmitter, and sharing identical intrinsic
      membrane properties, some heterogeneity was subsequently reported. The
      morphological diversity is generally acknowledged, but only two studies have
      shown functional differences between two classes of cells which vary in their
      ability to discharge in bursts. However, the location of the non-bursting cells
      was not characterized with anatomical techniques. Our recent work on the action
      of mu-opioid agonists in the thalamus revealed a widespread K+-mediated
      inhibition of most, if not all, thalamic relay and diffuse projection neurons.
      However, in the reticular nucleus, preliminary experiments suggested that the
      opioid sensitivity was variable. Based on these results and on observations of a
      discrete localization of mu-opioid receptors in the reticular nucleus, we
      investigated cellular heterogeneity within the nucleus using opioid agonists as
      markers. Using the whole cell patch clamp technique in young rat thalamic slices,
      we tested the responses of 28 neurons to opioids, the intrinsic membrane
      properties of each cell, and their relative location within the nucleus. Two
      types of intrinsic membrane properties underlying distinct discharge behaviours
      were seen in neurobiotin-labelled cells clearly located in the reticular nucleus:
      type I with the typical bursting behaviour previously reported in reticularis
      neurons, and type II in which bursting was greatly reduced or absent. Each class
      of cell could be further divided into subpopulations based on their opioid
      sensitivity. About half of both bursting (20) and non-bursting or tonic (8) cells
      were strongly inhibited by the mu-opioid receptor agonist D-Ala2,N-Me
      Phe4,glycinol5-enkephalin, an effect mediated by an increase in K+ conductance.
      At no time was inhibition by delta- or kappa-receptor agonists seen. Our work
      therefore further demonstrates that the reticular nucleus is functionally
      heterogeneous, although the role of such cell diversity has still to be
      determined.

PMID- 9145789
TI  - The phosphorylation of tau: a critical stage in neurodevelopment and
      neurodegenerative processes.

PMID- 9145790
TI  - Subthreshold oscillations and resonant behavior: two manifestations of the same
      mechanism.
AB  - The ability to generate subthreshold membrane potential oscillations in neurons
      from the inferior olive nucleus has been attributed to the electrical properties
      of these neurons, as well as to the properties of the network. In the present in
      vitro study we quantitatively characterized both intrinsic membrane and network
      properties that are directly involved in the oscillatory activity of olivary
      neurons in the guinea-pig. We also implemented an alternating current analysis to
      explore the resonance behavior of these neurons and to compare the resonant
      properties with the properties of the oscillatory activity. Spectral analysis,
      used for the quantitative characterization of the oscillatory activity under
      various experimental conditions, revealed that the pattern of the oscillatory
      activity is network specific rather than cell specific. These results are in
      agreement with the hypothesis that the oscillatory activity of olivary neurons is
      generated by a network of electrically coupled neurons. Using alternating current
      analysis, we found that impedance-frequency curves of olivary neurons demonstrate
      a peak impedance (resonance) at a frequency between 3 and 10 Hz, which
      corresponds to the frequency of the spontaneous oscillations. Like the
      spontaneous oscillations, this peak is tetrodotoxin insensitive, unaffected by K+
      channel blockers and almost completely blocked in the presence of Ni2+ in the
      physiological solution. Increasing the temperature increases the resonance
      frequency, as well as the frequency of the spontaneous oscillations. These
      results show that the resonant behavior of individual neurons is the basis of the
      oscillatory behavior of the network and that resonance can serve as a lumped
      parameter which encodes the oscillatory tendency of a neuron.

PMID- 9145791
TI  - Differential effects of acute and chronic electroconvulsive shock on the
      abundance of messenger RNAs for voltage-dependent potassium channel subunits in
      the rat brain.
AB  - The effect of acute and chronic electroconvulsive shock on the abundance of
      messenger RNAs encoding voltage-dependent potassium channel subunits in the rat
      brain was determined by in situ hybridization histochemistry with [35S]dATP
      labelled oligonucleotides at 6 h, 24 h and three weeks following the last shock.
      The messenger RNA abundance of two voltage-dependent potassium channel subunits,
      Kv1.2 and Kv4.2, was altered by electroconvulsive shock but in different ways. In
      acute electroconvulsive shock experiments, Kv1.2 and Kv4.2 messenger RNA
      abundance in the dentate gyrus were reduced 6 h following the shock and returned
      to control levels after 24 h. In chronic electroconvulsive shock-treated rats,
      Kv1.2 messenger RNA abundance showed similar changes to those in acute
      electroconvulsive shock: it was reduced 6 h after the last shock and had
      recovered after 24 h. Kv4.2 messenger RNA abundance in chronic electroconvulsive
      shock-treated rats, however, showed adaptive changes: 6 h after the last shock
      there were no changes in its abundance while 24 h after the last shock there was
      a significant increase in the dentate gyrus. The changes in Kv1.2 and Kv4.2
      messenger RNA abundance following electroconvulsive shock were only observed in
      the dentate gyrus and not in cornu ammonis 1 and cornu ammonis 3 of hippocampus
      or frontal-parietal cortex. Two other potassium channel subunits, Kv1.1 and
      Kv1.4, were not affected by either acute or chronic electroconvulsive shock.
      These findings indicate that acute and chronic electroconvulsive shock affect the
      gene expression of voltage-dependent potassium channel subunits with
      specificities for channel type, anatomical region and timing.

PMID- 9145792
TI  - Expression of glial glutamate transporters GLT-1 and GLAST is unchanged in the
      hippocampus in fully kindled rats.
AB  - In situ hybridization techniques and quantitative western blotting were used to
      study the expression of the glial glutamate transporter GLT-1 and GLAST in the
      brains of normal (implanted, non-kindled) and fully kindled rats. Wistar rats
      were implanted with stimulating electrodes in the basolateral amygdala, and
      killed 28 days after the stimulated group had shown stage 5 seizures on five
      occasions. The brains were processed for in situ hybridization of messenger RNA
      for GLT-1 using 35S-labelled oligonucleotide probes or digoxigenin-labelled
      riboprobes. Paired (kindled and non-kindled) sections were used for qualitative
      and quantitative analyses. Image analysis of autoradiograms showed no change in
      expression of GLT-1 messenger RNA in any region of the hippocampus or in the
      cortex. An increase in expression of GLT-1 messenger RNA (expressed as percentage
      difference of control) was observed bilaterally in the striatum in kindled
      animals (16-21%, P<0.05). Nuclear emulsion-dipped sections showed predominant
      glial cell labelling in the hippocampus. Particle density analysis revealed
      reduced cell labelling in some kindled vs control pairs but overall there was no
      significant reduction in labelling in CA1. Equivalent results were found in CA1
      using digoxigenin-labelled riboprobes. Quantitative immunoblotting also revealed
      no change in GLT-1 or GLAST transporter protein in the hippocampus of kindled
      animals. From these data we conclude that the enduring seizure susceptibility
      associated with the fully kindled state is unlikely to involve alterations in
      hippocampal GLT-1 messenger RNA or GLT-1 and GLAST transporter protein
      expression.

PMID- 9145793
TI  - Quantitation of AMPA receptor surface expression in cultured hippocampal neurons.
AB  - Protein and messenger RNA levels of the AMPA-type glutamate receptor subunits 1-3
      are high in many brain regions, but it is not known how much of the glutamate
      receptor protein is expressed on the surface of neurons in the form of functional
      receptors. To provide insight into this matter, western blot immunoreactivities
      for glutamate receptors 1 and 2/3, as well as binding of the specific ligand
      [3H]AMPA, were quantified following three independent treatments modifying
      surface receptors in intact primary hippocampal cultures: (i) proteolysis of
      surface receptors by chymotrypsin, (ii) cross-linking of surface receptors with
      the membrane-impermeant reagent bis(sulfosuccinimidyl)suberate, and (iii)
      biotinylation of surface receptors with the membrane-impermeant reagent
      sulfosuccinimidyl-2(biotinamido)ethyl-1,3-dithiopropionate. All three of these
      methods demonstrated that 60-70% of total glutamate receptor subunit 1 protein
      and 40-50% of total glutamate receptor 2/3 protein are expressed on the surface
      of hippocampal neurons. Parallel studies revealed that 52% of total [3H]AMPA
      binding sites could be precipitated with avidin beads following biotinylation of
      intact cultures, providing an estimate of [3H]AMPA binding site surface
      expression in accord with the estimates of the surface expression of glutamate
      receptor subunits 1-3. Experiments examining the surface expression of 32P
      labeled glutamate receptor subunit 1 demonstrated that approximately 65% of the
      phosphorylated form of the subunit is located in the plasma membrane, an estimate
      similar to the that derived via western blot for the entire glutamate receptor
      subunit 1 population in the same samples. Moreover, no significant change in the
      surface expression profile of the glutamate receptor subunits 1-3 was observed
      following stimulatory treatments known to increase glutamate receptor
      phosphorylation. These data indicate that slightly more than half of the AMPA
      receptors in cultured hippocampal neurons are located in the plasma membrane, and
      that AMPA receptor surface expression is not rapidly altered by glutamate
      receptor phosphorylation.

PMID- 9145794
TI  - Presence and differential internalization of two distinct insulin-like growth
      factor receptors in rat hippocampal neurons.
AB  - The pharmacological characteristics, localization and process of internalization
      of the insulin-like growth factor I and II receptors were studied in rat primary
      hippocampal cultured neurons grown under serum-free conditions. [125I]insulin
      like growth factor-I binding was specific with an apparent affinity (Kd) of 0.1
      nM and IC50 values of 0.1, 2.9 and 99.7 nM for insulin-like growth factor-I,
      insulin-like growth factor-II and insulin, respectively. The competition by
      insulin suggests the presence of genuine insulin-like growth factor-I receptors
      and not insulin-like growth factor binding proteins. In contrast, [125I]insulin
      like growth factor-II binding showed a Kd of 0.1 nM and IC50 values of 0.2 and
      20.5 nM for insulin-like growth factor-II and insulin-like growth factor-I while
      insulin was inactive, a well established characteristic of the insulin-like
      growth factor-II receptor. Using emulsion autoradiography, specific binding sites
      for [125I]insulin-like growth factor-I and -II were over the whole cultured
      neurons. The use of selective insulin-like growth factor-I and -II receptor
      antibodies further confirmed the existence of these receptors in rat hippocampal
      cultured neurons. To investigate the respective internalization profile of
      [125I]insulin-like growth factor-I and [125I]insulin-like growth factor-II
      receptor-ligand complexes in neurons, a technique of acid stripping was used. The
      apparent rate of endocytosis was found to be greater for the insulin-like growth
      factor-II than for the insulin-like growth factor-I receptor complexes. The
      internalization of [125I]insulin-like growth factor-I and [125I]insulin-like
      growth factor-II ligand-receptor complexes was confirmed using phenylarsine oxide
      which significantly blocked both internalization processes. In order to eliminate
      possible receptor recycling, monensin was used and shown to have no effect on the
      internalization of either ligand. Since the insulin-like growth factor-I receptor
      is coupled to tyrosine kinase activity, tyrphostin 47, a specific tyrosine kinase
      inhibitor. was used and shown to decrease [125I]insulin-like growth factor-I but
      not the [125I]insulin-like growth factor-II receptor internalization profile.
      Accordingly, insulin-like growth factor-I is apparently internalized mostly via
      the insulin-like growth factor-I tyrosine kinase type receptor, while insulin
      like growth factor-II is not. The insulin-like growth factor-II receptor ligand
      complex is likely internalized via a pathway possibly related to mannose
      phosphorylated residues as the insulin-like growth factor-II/mannose-6-phosphate
      receptor has been implicated in the intracellular targeting of lysosomal proteins
      containing glycosylated residues. Taken together, our results indicate that
      primary hippocampal cultured neurons represent a unique model for investigating
      the differential role and intracellular trafficking of both insulin-like growth
      factor-I and insulin-like growth factor-II receptor ligand complexes and their
      relevance to the respective functional role of these two-related trophic factors
      in the central nervous system.

PMID- 9145795
TI  - Lithium enhances synaptic transmission in neonatal rat hippocampus.
AB  - The effects of lithium on excitatory synaptic transmission were studied in the
      CA1 region of hippocampal slices taken from 14- to 30-day-old rats using
      extracellular recording techniques. Lithium (2-18 mM) reversibly increased the
      field excitatory postsynaptic potentials in a concentration-dependent manner.
      Application of lithium for 6-15 min had no effect on the synaptic input-output
      function, while application of lithium for 20-35 min shifted this curve to the
      left. Lithium reversibly increased the amplitude of the presynaptic fibre volley
      in a concentration- and calcium-dependent manner. Lithium decreased paired-pulse
      facilitation measured at 50-ms interstimulus intervals. The results indicate that
      lithium enhances excitatory synaptic transmission in CA1 pyramidal cells by at
      least two different actions.

PMID- 9145796
TI  - Evidence for involvement of the neuronal isoform of nitric oxide synthase during
      induction of long-term potentiation and long-term depression in the rat dentate
      gyrus in vitro.
AB  - The possible role of nitric oxide in the induction of long-term potentiation and
      long-term depression of field excitatory postsynaptic potentials in the dentate
      gyrus of the hippocampal slice has been investigated, in the rat, using two novel
      nitric oxide synthase inhibitors, 1-(2-trifluoromethylphenyl)imidazole, which is
      selective for the neuronal isoform in vitro, and 3-bromo-7-nitro-indazole. Long
      term potentiation was induced by a series of high-frequency trains, and long-term
      depression was induced by prolonged low-frequency stimulation at 1 Hz. The
      induction of long-term potentiation was inhibited by both 1-(2
      trifluoromethylphenyl)imidazole and 3-bromo-7-nitro-indazole at concentrations
      which did not alter the amplitude of the test excitatory postsynaptic potential.
      The inhibitory effect of 1-(2-trifluoromethylphenyl)imidazole on the induction of
      long-term potentiation was prevented by pretreatment with L-arginine, the
      substrate amino acid used by nitric oxide synthase for nitric oxide production.
      The induction of long-term depression was inhibited by both 3-bromo-7-nitro
      indazole and 1-(2-trifluoromethylphenyl)imidazole at concentrations which did not
      affect the test excitatory postsynaptic potential. The inhibitory effect of 1-(2
      trifluoromethylphenyl)imidazole was prevented by pretreatment with L-arginine.
      The present experiments provide strong support for the involvement of the
      neuronal isoform of nitric oxide synthase in the induction of long-term
      potentation and long-term depression.

PMID- 9145798
TI  - The frameshift mutation oscillator (Glra1(spd-ot)) produces a complete loss of
      glycine receptor alpha1-polypeptide in mouse central nervous system.
AB  - Mice homozygous for the recessive mutation oscillator (Glra1(spd-ot)) suffer from
      a complex motor disorder leading to death within three weeks after birth.
      Symptoms of this disorder mimic poisoning by strychnine, the antagonist of the
      inhibitory glycine receptor. The syndrome has previously been correlated to a 7
      base pair microdeletion within the Glra1 gene (chromosome 11) encoding the alpha1
      subunit of the adult glycine receptor isoform. As shown by [3H]strychnine binding
      and western blot analysis employing subunit-specific antibodies, spinal cord of
      homozygous oscillator mice was totally devoid of alpha1-polypeptide,
      characterizing the Glra1(spd-ot) gene as a functional null allele of Glra1.
      Moreover, tissue levels of the postsynaptic anchoring protein gephyrin were
      drastically reduced in the Glra1(spd-ot)/Glra1(spd-ot) genotype. In contrast,
      immunoanalysis revealed a persisting low-level expression of non-alpha1 glycine
      receptor polypeptides. Spinal glycine receptor content was also significantly
      reduced in the +/Glra1(spd-ot) genotype. This reduction coincided with increased
      acoustic startle responses in heterozygous animals consistent with haplotype
      insufficiency of glycine receptor function. Lethality of the murine null allele
      Glra1(spd-ot) contrasts with the situation in the human, where homozygosity for a
      GLRA1 null allele produces the phenotype of the non-lethal disorder hyperekplexia
      (startle disease; stiff baby syndrome). This suggests a disparate regulation of
      glycine receptor subunit genes and/or diverse compensatory pathways in mice and
      humans.

PMID- 9145797
TI  - Distribution of calretinin-containing neurons relative to other neurochemically
      identified cell types in the medial septum of the rat.
AB  - The topographic distribution of calretinin-immunoreactive neurons was studied in
      the medial septum diagonal band of Broca complex of the rat, in relation to the
      localization of other neurochemically identified cell groups containing choline
      acetyltransferase, parvalbumin or calbindin D28k. Double-labelling experiments
      revealed that these four antigen-containing cells formed distinct dorsoventrally
      running lamellae overlayed on top of each other similar to onion leaves. There
      was only a slight overlapping of the various cell groups. None of the four
      antigens were co-localized in the same cells. The lamella occupied by calretinin
      positive neurons is situated at the border of the medial septum and the
      intermediolateral septal nucleus, and shows some overlap with the area occupied
      by cholinergic neurons. Retrograde transport of horseradish peroxidase from the
      hippocampus combined with immunostaining for calretinin revealed that calretinin
      containing neurons do not participate in the septohippocampal projection. The
      lack of projection to the amygdala was also confirmed. Thus, calretinin
      containing neurons represent a distinct cell group in the medial septal region,
      which either projects to subcortical areas, or may function as interneurons
      relaying hippocampal feedback to the medial septal projection neurons.

PMID- 9145799
TI  - Pituitary adenylate cyclase-activating polypeptide promotes cell survival and
      neurite outgrowth in rat cerebellar neuroblasts.
AB  - High concentrations of pituitary adenylate cyclase-activating polypeptide (PACAP)
      and its receptors have been detected in the rat cerebellum during ontogenesis. In
      particular, PACAP receptors are actively expressed in immature granule cells,
      suggesting that PACAP may act as a neurotrophic factor in the developing rat
      cerebellum. In the present study, we have investigated the effect of PACAP on
      cell survival and neurite outgrowth in cultured immature cerebellar granule
      cells. In control conditions, cultured granule cells undergo programmed cell
      death. Exposure of cultured cells to PACAP for 24 and 48 h provoked a significant
      increase in the number of living cells. The effect of PACAP on cell survival was
      inhibited by the PACAP antagonist PACAP(6-38). Vasoactive intestinal polypeptide
      was approximately 1000 times less potent than PACAP in promoting cell survival.
      PACAP also induced a significant increase in the number of processes and in the
      cumulated length of neurites borne by cultured neuroblasts. The present results
      demonstrate that PACAP promotes cell survival and neurite outgrowth in cultured
      immature granule cells. Since PACAP and its receptors are expressed in situ in
      the rat cerebellar cortex, these data strongly suggest that PACAP plays a
      physiological role in the survival and differentiation of cerebellar granule
      cells.

PMID- 9145800
TI  - Expression of brain-derived neurotrophic factor protein in the adult rat central
      nervous system.
AB  - We have generated and characterized a multi-functional polyclonal anti-brain
      derived neurotrophic factor antibody. Western blot analysis, dorsal root ganglion
      neurite outgrowth and dorsal root ganglion neuron survival assays showed that
      this antibody specifically recognized brain-derived neurotrophic factor and not
      the other neurotrophins. Furthermore, it was capable of blocking the functional
      effects of brain-derived neurotrophic factor. Using this antibody, we examined
      the expression of brain-derived neurotrophic factor in adult rat brains by
      immunohistochemistry. We found distinct brain-derived neurotrophic factor
      immunoreactivity in several structures of the brain. These included the
      neocortex, piriform cortex, amygdaloid complex, hippocampal formation, claustrum,
      some thalamic and hypothalamic nuclei, the substantia nigra and some brainstem
      structures. In contrast to brain-derived neurotrophic factor messenger RNA
      expression, brain-derived neurotrophic factor immunoreactivity was also found in
      the lateral septum, bed nucleus of the stria teminalis, medial preoptic nucleus,
      olivery pretectal nucleus, lateral paragigantocellular nucleus and the dorsal
      horn of the spinal cord. In normal adult rat brains, there was little or no
      staining in the CA1 region or the granule cell layer of the dentate gyrus of the
      hippocampus. However, kainate treatments greatly increased brain-derived
      neurotrophic factor immunoreactivity in the pyramidal cells of the CA1 region, as
      well as in the dentate gyrus, CA2 and CA3 hippocampal regions. We present
      evidence for both the subcellular localization and anterograde transport of
      endogenous brain-derived neurotrophic factor in the central nervous system. The
      detection of brain-derived neurotrophic factor protein in several discrete
      regions of the adult brain, and brain-derived neurotrophic factor's dramatic up
      regulation following kainate treatment, strongly supports a role of brain-derived
      neurotrophic factor in the maintenance of adult neurons and synapses. Since
      several populations of neurons lost during neurodegenerative diseases synthesize
      brain-derived neurotrophic factor protein, modulation of brain-derived
      neurotrophic factor levels may be clinically beneficial. The antibody described
      in this paper will be helpful in determining more precisely the functional
      activities of brain-derived neurotrophic factor in the adult.

PMID- 9145801
TI  - The role of nerve growth factor in a model of visceral inflammation.
AB  - There is growing evidence that nerve growth factor may be an important mediator
      of the sensory disorders associated with inflammation. This hypothesis was tested
      in a rat model of cystitis. In this model, an experimental inflammation is
      created in anaesthetized rats with an irritant chemical. Within 1 h, bladder
      reflexes, activated by the sensory innervation of this viscus, become
      exaggerated, mimicking the disorders seen in humans with chronic cystitis. The
      development of this hyper-reflexia following experimental inflammation was
      quantified using the technique of repeated cystometrograms. By several measures,
      bladder reflex excitability increased about three-fold after 5 h. Firstly, the
      study investigated whether inflammatory changes can be prevented by
      pharmacological antagonism of nerve growth factor. A synthetic fusion protein was
      used, consisting of the extracelluar domain of the high-affinity nerve growth
      factor receptor, trkA, coupled to the Fc portion of an immunoglobulin. Previous
      work has shown that this molecule can sequester nerve growth factor and reduce
      its bioavailability both in vitro and in vivo. Treatment of animals with the
      fusion molecule at 1 mg/kg, immediately before inflammation of the bladder,
      largely, and very significantly, prevented the expected increases in reflex
      excitability of this organ. Pretreatment with a related fusion protein, capable
      of sequestering the neurotrophin brain-derived neurotrophic factor and
      neurotrophin-4/5, but not nerve growth factor, was without effect. Similarly, a
      control fusion molecule, without neurotrophin-sequestering capacity, did not
      reduce the inflammation-induced hyper-reflexia. Systemic treatment with the nerve
      growth factor-sequestering molecule, but not control molecules, partially and
      significantly reversed established inflammatory changes, by about 30-60%,
      depending on outcome measure. The nerve growth factor-sequestering protein had no
      significant effects on bladder reflex excitability in the uninflamed state. It
      was also without significant effect on capsaicin-induced contractions of the
      urinary bladder. Administration of exogenous nerve growth factor into the lumen
      of the urinary bladders of normal anaesthetized rats produced a rapid and marked
      bladder hyper-reflexia similar to that seen with experimental inflammation. These
      findings are consistent with other circumstantial evidence that nerve growth
      factor may interact with visceral sensory systems. Together, the data strongly
      suggest that nerve growth factor produced in inflamed tissues is a critical
      mediator of the sensory disorders associated with inflammation.

PMID- 9145803
TI  - Expression of neurotransmitter genes in rat spinal motoneurons after
      chemodenervation with botulinum toxin.
AB  - Botulinum toxin is widely used for the treatment of focal movement disorders,
      where chemodenervation is used to decrease hyperactivity in selected muscles.
      Beside a focal paresis, widespread effects on neuromuscular synaptic function
      have been demonstrated. However, reactions of motoneurons after neuromuscular
      chemodenervation without gross morphological lesions are largely unknown.
      Peripheral axotomy, in contrast, leads to profound changes in the expression of
      several genes, including those encoding neurotransmitters, in motoneurons. We
      therefore examined the expression of neurotransmitter genes in rat motoneurons
      six days after intramuscular botulinum toxin application in the right
      gastrocnemius muscle. Similar doses of botulinum toxin as used in human where
      injected. A focal bilateral increase in expression of the choline
      acetyltransferase gene and a widespread bilateral increase of the beta-calcitonin
      gene-related peptide and the enkephalin genes was measured in motoneurons after
      botulinum toxin injection. Cholecystokinin had a lower expression after botulinum
      toxin injections. Growth-associated protein 43, nitric oxide synthase,
      somatostatin and proopiomelanocortin messenger RNA were not found in motoneurons
      of both groups. Our results demonstrate that changes in the expression of
      neurotransmitter genes in motoneurons also occur after chemodenervation but with
      different patterns to those found after mechanical nerve lesioning. These changes
      reflect focal and widespread modulative events. The knowledge of these events
      should lead to a better understanding of the focal paralysis and of the more
      widespread effects found in human after intramuscular injection of botulinum
      toxin.

PMID- 9145802
TI  - Inhibition of spinal nitric oxide synthase by N(omega)-nitro-L-arginine blocks
      the release of Met-enkephalin and antinociception induced by supraspinally
      administered beta-endorphin in the rat.
AB  - The antinociception induced by beta-endorphin given supraspinally has been
      demonstrated previously to be mediated by the release of Met-enkephalin acting on
      delta2-opioid receptors in the spinal cord. The present study was designed to
      determine the role of nitric oxide in the spinal cord on beta-endorphin-induced
      release of Met-enkephalin and antinociception. The experiments were performed in
      pentobarbital-anesthetized rats. The release of Met-enkephalin was performed
      using a spinal cord perfusion technique and the Met-enkephalin released in the
      spinal perfusates was measured by radioimmunoassay. Antinociception was assessed
      by the tail-flick test. beta-Endorphin (2 microg) given intraventricularly
      induced the release of Met-enkephalin from the spinal cord. The release of Met
      enkephalin was dose-dependently attenuated by N(omega)-nitro-L-arginine (0.1 nM-1
      microM) added into spinal perfusates and the attenuation was reversed by
      intrathecally applied L-arginine. The stereoisomer N(omega)-nitro-D-arginine
      given intrathecally, however, did not inhibit the release of Met-enkephalin
      induced by intraventricularly administered beta-endorphin. beta-Endorphin (4
      microg) given intraventricularly produced antinociception in rats pretreated
      intrathecally with saline. The antinociception induced by beta-endorphin was
      blocked by intrathecally administered N(omega)-nitro-L-arginine (5 microg) and
      the blockade of antinociception was reversed by intrathecal injection of L
      arginine (50 microg). N(omega)-Nitro-D-arginine (5 microg) given intrathecally
      did not block the intraventricularly administered beta-endorphin-induced
      antinociception. N(omega)-Nitro-L-arginine (10 microg) given intraventricularly
      did not affect intraventricularly administered beta-endorphin-induced Met
      enkephalin release nor did it affect intraventricular beta-endorphin-induced
      antinociception, indicating that the effect of N(omega)-nitro-L-arginine is not
      at supraspinal sites. Intrathecal pretreatment with N(omega)-nitro-L-arginine did
      not affect intrathecally administered [D-Ala2]deltorphin II-induced
      antinociception. Our results indicate that N(omega)-nitro-L-arginine given
      intrathecally attenuates intraventricular beta-endorphin-administered inhibition
      of the tail-flick response by presynaptically inhibiting the release of Met
      enkephalin.

PMID- 9145804
TI  - Localization of bradykinin-like immunoreactivity in the rat spinal cord: effects
      of capsaicin, melittin, dorsal rhizotomy and peripheral axotomy.
AB  - A putative role for bradykinin has been proposed in the processing of sensory
      information at the level of the spinal cord. Autoradiographic studies have
      demonstrated the presence of B2 kinin receptor binding sites in superficial
      laminae of the dorsal horn and a down-regulation of those receptors in rat models
      of pain injury. In this study, classical immunocytochemistry and confocal
      microscopy immunofluorescence were used first to localize bradykinin-like
      immunoreactivity in all major spinal cord segments of naive rats; second, to
      assess bradykinin-like immunoreactivity changes that occur in animals subjected
      to various chemical treatments and surgical lesions. High densities of bradykinin
      like immunoreactivity were observed in motoneuron of the ventral horn, deeper
      laminae and nucleus dorsalis of the dorsal horn. Higher magnification of ventral
      horn showed strong immunostaining of motoneuron perikaryas and their proximal
      processes. Two types of bradykinin-like immunoreactivity immunostained cellular
      bodies were observed in deeper laminae of the dorsal horn. These interneurons,
      morphologically corresponding to islets and antenna-type cells project dendrites
      to adjacent laminae. Furthermore, numerous strongly marked dendrites,
      transversally cut, suggest the presence of projection neurons to higher cervical
      centres. Following unilateral lumbar dorsal rhizotomy (L1-L6) or peripheral
      lesion of the sciatic nerve, important increases of bradykinin-like
      immunoreactivity were found in laminae III and IV of the ipsilateral dorsal horn.
      In contrast, significant decreases of immunodeposits were observed in both cell
      bodies and numerous dendrites of motoneuron surrounding neuropil. Specific
      destructions of sensory afferent fibres with capsaicin or selective activation of
      kallikreins with melittin caused increases of bradykinin-like immunoreactivity in
      both the dorsal and ventral horns of the spinal cord. These results which
      demonstrate the cellular localization of bradykinin-like immunoreactivity in both
      dorsal and ventral horns of the rat spinal cord, further reveal the plasticity of
      this non-sensory peptidergic system following various chemical and surgical
      treatments. Hence, these anatomical findings along with earlier functional and
      receptor autoradiographic studies reinforce the putative role of bradykinin in
      sensory function.

PMID- 9145805
TI  - Distribution of vasopressin and oxytocin receptors in the rat spinal cord: sex
      related differences and effect of castration in pudendal motor nuclei.
AB  - The distribution of vasopressin and oxytocin receptors was established by in
      vitro autoradiography in the spinal cord of adult rats of either sex, as well as
      in male castrates. In both males and females, high concentrations of vasopressin
      binding sites were found in a few groups of somatic motoneurons: the large
      lateral group at the cervicothoracic junction in segments C8 and Th1; the small
      medial group in segments L3-L5; and the pudendal and retrodorsolateral nuclei in
      segments L5-L6. The extension and intensity of labelling in pudendal nuclei were
      markedly lower in females than in males, in particular in the dorsomedial
      nucleus, where binding was either not or hardly detectable. Gonadectomy in males
      resulted in a significant reduction of binding in pudendal nuclei, but not in
      other labelled motor nuclei. Moderate amounts of vasopressin binding sites were
      also found evenly distributed throughout the central gray at all segmental
      levels. Oxytocin binding sites were detectable in all spinal segments, but in low
      amounts and restricted to the superficial layers of the dorsal horn. The
      abundance of vasopressin binding sites in the central gray suggests that
      vasopressin may be involved in most spinal functions. The permanent expression of
      vasopressin binding sites in pudendal motor nuclei of is particular interest with
      regard to the known plasticity of pudendal motoneurons.

PMID- 9145806
TI  - Multiple voltage-dependent calcium currents in acutely isolated mouse vestibular
      neurons.
AB  - We investigated the presence of voltage-gated calcium currents in vestibular
      neurons acutely isolated from postnatal mice vestibular ganglions using the whole
      cell patch-clamp technique. The neuronal origin of the recorded cells was
      confirmed by immunohistochemical detection of neurofilaments and calretinin. High
      and low voltage-activated calcium currents were recorded. High voltage-activated
      currents were present in all investigated neurons. Low voltage-activated currents
      were recorded in only a few large vestibular neurons. High and low voltage
      activated currents were distinguished by their thresholds of activation and their
      ability to run-up during early recordings. Among high voltage-activated currents.
      L-, N- and P-type currents were identified by their sensitivity to, respectively,
      the dihydropyridines agonist Bay K 8644 (3 microM) and antagonist nitrendipine (3
      microM), the co-conotoxin GVIA (3 microM) and the omega-agatoxin IVA at low
      concentration (50 nM). An inactivating current sensitive to 1 microM omega
      agatoxin IVA with characteristics similar to those of the Q-type current was also
      recorded in vestibular neurons. When L-, N-, P-, Q-type barium currents were
      blocked, a residual high voltage-activated current defined by its resistance to
      saturating concentrations of all above blockers was detected. This residual
      current was completely blocked by 0.5 mM nickel and cadmium. Our results reveal
      that primary vestibular neurons express a variety of voltage-activated calcium
      currents with distinct physiological and pharmacological properties. This
      diversity could be related both with their functional synaptic characteristic,
      and with the intrinsic physiological properties of each class of vestibular
      afferents.

PMID- 9145808
TI  - Evidence for the co-localization of another connexin with connexin-43 at
      astrocytic gap junctions in rat brain.
AB  - Gap junctions between astrocytes as well as between astrocytes and
      oligodendrocytes in rat brain were immunohistochemically labelled with a
      monoclonal and an affinity-purified polyclonal antibody generated against
      connexin-26. By light microscopy, the immunolabelling patterns obtained were,
      with a few exceptions, remarkably similar to previously described distribution
      patterns of the gap junctional protein connexin-43, which is expressed by
      astrocytes and is localized at astrocytic gap junctions. By electron microscopy,
      immunoreactivity with these two anti-connexin-26 antibodies was restricted to
      astrocytes; inter-astrocytic gap junctional membranes were symmetrically
      labelled, heterologous oligo-astrocytic junctional membranes were asymmetrically
      labelled only on the astrocyte side and oligo-oligodendrocyte junctions were
      unlabelled. Two additional anti-connexin-26 antibodies that were found to produce
      punctate labelling in leptomeninges and liver failed to do so in brain
      parenchyma, consistent with reports indicating the absence of authentic connexin
      26 in this tissue. Antibodies that labelled astrocytic gap junctions exhibited no
      cross-reaction with connexin-43 or connexin-32, as demonstrated by western
      blotting, but recognized liver connexin-26 as well as several brain proteins,
      including an approximately 32000 mol. wt protein that did not correspond to
      connexin-32 and a 26000 mol. wt protein that co-migrated with liver connexin-26.
      These results suggest that connexin-26, or more likely a protein having sequence
      homology with connexin-26, is targeted to astrocytic gap junctions and raise the
      possibility of the existence of connexins that may be co-expressed with connexin
      43 in most, but perhaps not all, astrocytes.

PMID- 9145807
TI  - Control of Ca2+ channel current and exocytosis in rat lactotrophs by basally
      active protein kinase C and calcineurin.
AB  - Modulation of voltage-activated Ca2+ channel activity by phosphorylation was
      studied in metabolically intact voltage-clamped rat lactotrophs. Experiments
      using Ba2+ as a charge carrier indicated that a phorbol ester protein kinase C
      activator stimulates high-voltage-activated Ca2+ channel currents, but has no
      effect on low-voltage-activated currents. Extracellular application of
      structurally and mechanistically distinct protein kinase C inhibitors
      (staurosporin, H7, calphostin C, chelerythrine and Ro 31-8220) preferentially
      inhibited the high-voltage-activated Ba2+ current. This suggests that protein
      kinase C is required for maintainance of Ca2+ channel activity even in the
      absence of modulators. Cyclosporin A, an inhibitor of the Ca2+/calmodulin
      dependent protein phosphatase calcineurin, increased the high-voltage-activated
      Ca2+ channel current, and staurosporin reversed this effect. Thus,
      dephosphosphorylation by calcineurin may limit basal Ca2+ channel activity. Time
      domain monitoring of cellular capacitance changes demonstrated that cyclosporin A
      and 12-O-tetradecanoyl-phorbol-13-acetate do not affect exocytosis at a
      hyperpolarized potential, but each enhances depolarization-induced exocytosis.
      Facilitation of exocytosis by cyclosporin A differed from 12-O-tetradecanoyl
      phorbol-13-acetate in that it was biphasic. The delayed facilitation induced by
      cyclosporin A could be accounted for by stimulation of the voltage-gated Ca2+
      current. These results suggest that the high-voltage activated Ca2+ channel
      current in rat lactotrophs is determined by the opposing basal activities of
      protein kinase C and calcineurin. Furthermore, it is concluded that the
      regulation of Ca2+ channels by protein kinase C and calcineurin affects
      depolarization-induced exocytosis.

PMID- 9145809
TI  - Ultrastructural studies of an immune-mediated inflammatory response in the CNS
      parenchyma directed against a non-CNS antigen.
AB  - We have shown previously that heat-killed bacillus Calmette-Guerin injected into
      the brain parenchyma becomes sequestered behind the blood brain barrier for
      months undetected by the immune system. However, independent peripheral
      sensitization of the immune system to bacillus Calmette-Guerin results in
      recognition of bacillus Calmette-Guerin in the brain and the induction of focal
      chronic lesions [Matyszak M. K. and Perry V. H. (1995) Neuroscience 64, 967 977].
      We carried out ultrastructural studies of these lesions. Prior to subcutaneous
      challenge we used immunohistochemistry to detect bacillus Calmette-Guerin which
      was found in cells with the morphology of macrophages/microglia and in
      perivascular macrophages. Eight to 14 days after subcutaneous challenge there was
      a conspicuous leucocyte infiltration at the site of bacillus Calmette-Guerin
      deposits within the brain parenchyma. The majority of these cells were
      macrophages and lymphocytes, with some lymphocytes showing characteristic blast
      morphology. Dendritic cells in close contact with lymphocytes were prominent.
      Inflammatory cells were found in perivascular cuffs and within the brain
      parenchyma. The tissue was oedematous and some axons were undergoing Wallerian
      degeneration with associated myelin degeneration. Throughout the lesions, but
      more commonly at the edges, we detected macrophages containing myelin in their
      cytoplasm close to intact axons and axons with evidence of remyelinating sheaths,
      suggestive of primary demyelination. In older lesions, two to three months after
      the peripheral challenge, the oedema was less pronounced and there was little
      evidence of Wallerian degeneration. There were still many macrophages.
      lymphocytes and dendritic cells, although the number of these cells was lower
      than in earlier lesions. Late lesions also contained many plasma cells which were
      not present in early lesions. In these late lesions there were bundles of axons
      with no myelin or a few axons with thin myelin sheaths, suggestive of persistent
      or ongoing demyelination or remyelination. These observations show that, during a
      delayed-type hypersensitivity lesion in the CNS, the leucocyte populations change
      with time, and suggest that the mechanisms and type of tissue damage are
      different in the early and late stages of the lesion.

PMID- 9145810
TI  - Expression of myelin-associated glycoprotein transcripts in murine
      oligodendrocytes.
AB  - The recognition molecule myelin-associated glycoprotein is expressed by
      oligodendrocytes, the myelinating cells of the central nervous system. The myelin
      associated glycoprotein gene gives rise to two alternatively spliced transcript
      variants ("early" and "late" message) which are developmentally regulated. In
      this study, using mice, we investigated whether both transcripts can be expressed
      in an individual oligodendrocyte or whether different oligodendrocyte populations
      exist expressing either one or the other myelin-associated glycoprotein messenger
      RNA. For this purpose the cytoplasmic RNA content of single oligodendrocytes
      derived either from cultures of embryonic mouse brain or from the corpus callosum
      murine slice preparation was harvested during patch-clamping in the whole-cell
      recording mode by applying negative pressure to the patch pipette. After reverse
      transcription, cDNA fragments were amplified by the polymerase chain reaction and
      analysed by agarose gel electrophoresis and restriction enzyme maps. Expression
      of myelin-associated glycoprotein transcripts could first be detected in those
      oligodendrocytes which already had acquired a more mature developmental stage.
      This stage could electrophysiologically be characterized by the dominance of
      passive K+ currents. In addition to oligodendrocytes expressing only the late or
      the early transcript, many cells were found expressing simultaneously both
      transcripts with varying levels. The myelin-associated glycoprotein transcript
      expression is therefore found to be developmentally regulated at a stage when
      oligodendrocytes have already acquired the channel properties of the adult.

PMID- 9145811
TI  - Region-specific developmental patterns of atrial natriuretic factor- and nitric
      oxide-activated guanylyl cyclases in the postnatal frontal rat brain.
AB  - In the rat central nervous system, cyclic GMP can be produced by two isoforms of
      guanylyl cyclase: a cytosolic isoform, which is activated by nitric oxide, and a
      membrane-bound isoform, activated by atrial natriuretic factor. We studied the
      development of guanylyl cyclase activity upon maturation of the rat forebrain
      from postnatal days 4 to 24, using a combined immunocytochemical and biochemical
      approach. Atrial natriuretic factor-activated particulate guanylyl cyclase
      activity was found to decrease in the frontal cortex, in the lateral septum and
      in the piriform cortex upon maturation. A transient expression of atrial
      natriuretic factor-sensitive guanylyl cyclase activity was observed at postnatal
      day 8 in the caudate putamen complex, whereas an increase was observed in the
      lateral olfactory tract from postnatal days 8 to 24. Biochemical and
      immunocytochemical studies using the nitric oxide synthase inhibitor N(G)-nitro-L
      arginine methyl ester, or the inhibitor of soluble guanylyl cyclase 1H
      [1,2,4]oxadiazolo[4,3-a]quinaloxin-1-one, indicated high levels of endogenous
      nitric oxide release at postnatal days 4 and 8. This activity decreased strongly
      in all brain areas examined. From postnatal day 8 onwards, atrial natriuretic
      factor-responsive cyclic GMP-immunoreactive cells could be characterized as
      astrocytes, with the exception of those in the the lateral olfactory tract, where
      the myelinated fibers became cyclic GMP producing. Furthermore, our results on
      activation of both guanylyl cyclases at postnatal day 8 leads to the suggestion
      that both isoforms might be found in the same cells. This study shows that there
      are pronounced differences between various frontal brain areas in the development
      of the responsiveness of both the particulate and soluble isoforms of guanylyl
      cyclase, and lends further support to the hypothesis that natriuretic peptides
      have a role in neuronal growth and plasticity of the rat brain.

PMID- 9145812
TI  - Ion homeostasis in brain cells: differences in intracellular ion responses to
      energy limitation between cultured neurons and glial cells.
AB  - Intracellular concentrations of sodium, potassium and calcium together with
      membrane potentials were measured in cultured murine cortical neurons and glial
      cells under conditions which mimicked in vivo hypoxia, ischemia and hypoglycemia.
      These included; glucose omission with and without added pyruvate, addition of
      rotenone in the presence and absence of glucose and substitution of 2
      deoxyglucose for glucose with and without rotenone. Cellular energy levels
      ([ATP], [ADP], [phosphocreatine], [creatine]) were measured in suspensions of C6
      cells incubated in parallel under identical conditions. [Na+]i and [Ca2+]i rose
      while [K+]i fell and plasma membrane depolarized when energy production was
      limited. Intracellular acidification was observed when glycolysis was the sole
      source for ATP synthesis. There was a positive correlation between the extent of
      energy depletion in glial cells and the magnitude and velocity of alterations in
      ion levels. Neither glycolysis alone nor oxidative phosphorylation alone were
      able to ensure unaltered ion gradients. Since oxidative phosphorylation is much
      more efficient in generating ATP than glycolysis, this finding suggests a
      specific requirement of the Na pump for ATP generated by glycolysis. Changes in
      [Na+]i and [K+]i observed during energy depletion were gradual and progressive
      whereas those in [Ca2+]i were initially slow and moderate with large elevations
      occurring only as a late event. Increases in [Na+]i were usually smaller than
      reductions in [K+]i, particularly in the glia, suggestive of cellular swelling.
      Glia were less sensitive to identical insults than were neurons under all
      conditions. Results presented in this study lead to the conclusion that the
      response to energy deprivation of the two main types of brain cells, neurons and
      astrocytes, is a complex function of their capacity to produce ATP and the
      activities of various pathways which are involved in ion homeostasis.

PMID- 9145813
TI  - Excitation of hypoglossal motoneurons responsible for tongue protrusions is
      associated with palatally induced jaw-closing reflex.
AB  - The excitation of hypoglossal motoneurons innervating the genioglossus and
      geniohyoid muscles during transient jaw closing, the so-called jaw-closing
      reflex, was studied in cats. The application of diffuse pressure stimulation to
      the posterior palatal surface produced the jaw-closing reflex, and it was found
      that mechanosensory inputs from the posterior palatal mucosa sent excitatory
      synaptic inputs to both genioglossus and geniohyoid motoneurons. We demonstrated
      that, during the palatally induced jaw-closing reflex, the tongue extended at jaw
      closure and was still extended forward in the initial part of the opening phase.
      In five of 27 genioglossus motoneurons and nine of 23 geniohyoid motoneurons, the
      onset of burst was elicited before the onset of jaw closure. The remaining cells
      produced the onset of burst in the closing phase and in the initial part of the
      occlusal phase. However, the onset of excitatory postsynaptic potentials was 75
      180 ms (n=20), earlier than that of jaw closure. During the jaw-closing reflex,
      the genioglossus and geniohyoid motoneurons were excited during the same phase of
      jaw movements and there was no difference in the onset of firing between the
      genioglossus and geniohyoid motoneurons. It is concluded that the excitation of
      the genioglossus and geniohyoid motoneurons may be associated with tongue
      protrusions during the palatally induced jaw-closing reflex.

PMID- 9145814
TI  - The ontogeny of NADPH-diaphorase neurons in serum-free striatal cultures
      parallels in vivo development.
AB  - Nitric oxide synthase is co-localized with somatostatin and neuropeptide Y in a
      subpopulation of striatal interneurons that stain selectively for NADPH
      diaphorase. We studied the ontogeny of diaphorase-positive neurons in striatal
      serum-free cultures derived from 15-16-day-old CD1 mice. NADPH-diaphorase
      staining was detected as early as embryological day 18 in vivo and day 5 in
      vitro. Over the next seven days the number of neurons staining for NADPH
      diaphorase increased rapidly and then levelled off at about 0.5-1% of the total
      neuronal population both in vivo and in vitro. The cultured diaphorase neurons
      were also similar to their in vivo counterparts in terms of morphology and
      dendritic branching. Striatal neurons expressing NADPH-diaphorase exhibit similar
      ontogeny, morphology and neurochemical characteristics in vivo and in serum-free
      primary neuronal cultures. The culture system may represent a useful model for
      studying this important subgroup of striatal neurons.

PMID- 9145815
TI  - Sequential antimicrobial therapy--the role of quinolones.

PMID- 9145816
TI  - The activity of the methylpiperazinyl fluoroquinolone CG 5501: a comparison with
      other fluoroquinolones.
AB  - The in-vitro activity of CG 5501 against a wide range of recent clinical isolates
      was compared with that of three fluoroquinolones. CG 5501 inhibited 90% of the
      species of the family Enterobacteriaceae at 0.5 mg/L or less, exceptions being
      Enterobacter spp. (MIC90 2 mg/L) and Serratia spp. (MIC90 4 mg/L). Ninety per
      cent of Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter
      spp. were inhibited by 16, 4 and 1 mg/L respectively. CG 5501 had high activity
      against Gram-positive cocci, 90% of staphylococci being inhibited at 2 mg/L.
      Methicillin-resistant Staphylococcus aureus strains were generally ciprofloxacin
      resistant yet were all susceptible to 4 mg/L or less of CG 5501. Isolates of
      Streptococcus pneumoniae were eight-fold more susceptible to CG 5501 (MIC90 0.5
      mg/L) than to ciprofloxacin (MIC90 4 mg/L) and the former had a similar activity
      to that of trovafloxacin and sparfloxacin. Enterococcus faecalis was generally
      two- to four-fold more susceptible to CG 5501 or trovafloxacin than to
      ciprofloxacin. CG 5501 and trovafloxacin had high activity against Bacteroides
      fragilis (MIC90 0.25 mg/L). Five strains of Chlamydia spp. were inhibited by < or
      =0.12 mg/L of CG 5501; sensitive and multiresistant strains of Mycobacterium
      tuberculosis were inhibited by < or =0.5 mg/L of CG 5501. The high activity and
      breadth of its antibacterial spectrum suggests that CG 5501 should be useful in a
      wide range of clinical infections.

PMID- 9145817
TI  - Effect of pH and buffer system on the in-vitro activity of five antifungals
      against yeasts.
AB  - We have compared the effect of various media on the in-vitro activity of
      amphotericin B, flucytosine, fluconazole, itraconazole and ketoconazole against
      93 clinical yeast isolates by a micro-broth dilution technique. The media used
      were: RPMI 1640 with 2% glucose, buffered with 0.165 M MOPS at pH 7.0; the same
      medium, but buffered at pH 7.4; and the same medium, but buffered at pH 7.4 with
      0.15% sodium bicarbonate. The three media gave similar results with azole
      antifungals and flucytosine, but the medium buffered at pH 7.0 failed to detect
      different populations of yeasts with respect to amphotericin B susceptibility. In
      the case of the media buffered at pH 7.4, Candida krusei was significantly less
      susceptible to amphotericin B than Candida albicans or Torulopsis glabrata. We
      could not evaluate the results obtained with Candida parapsilosis and
      Cryptococcus neoformans since these species did not grow adequately in all three
      media.

PMID- 9145818
TI  - In-vitro study of the synergy between beta-lactam antibiotics and glycopeptides
      against enterococci.
AB  - The synergy between glycopeptides and beta-lactams was studied using different
      techniques such as broth macrodilution, killing curves and agar dilution combined
      with agar diffusion. Two glycopeptide-resistant enterococci isolated from
      different clinical samples were used. Results showed different effects with
      significant changes in MICs. Antibacterial activity was related to the
      concentration of glycopeptide and beta-lactam for Enterococcus faecalis 8253,
      while for Enterococcus faecium 8072 a paradoxical effect was observed. With this
      strain, the best synergic effect was detected at teicoplanin concentrations of 1
      4 mg/L, but antibacterial activity was reduced at concentrations of 8, 16 and 32
      mg/L. No synergic effect was observed with vancomycin. The combination of agar
      dilution with agar diffusion techniques may constitute a simple method for
      routine detection of synergic effects between glycopeptides and beta-lactams.

PMID- 9145819
TI  - Comparative studies of the bactericidal, morphological and post-antibiotic
      effects of arbekacin and vancomycin against methicillin-resistant Staphylococcus
      aureus.
AB  - Arbekacin, an aminoglycoside antibiotic, has antibacterial activity against both
      Gram-positive and Gram-negative bacteria and is stable in the presence of
      aminoglycoside-inactivating enzymes produced by methicillin-resistant
      Staphylococcus aureus (MRSA). In this report, the antibacterial activity of
      arbekacin was compared with that of vancomycin, a glycopeptide antibiotic that
      also has potent antibacterial activity against MRSA. Arbekacin showed
      concentration-dependent bactericidal activity against MRSA strain 1936 (0.5-2 x
      MIC), but vancomycin showed only slight bactericidal activity, even at high
      concentrations of 19 x MIC. Arbekacin showed a longer post-antibiotic effect (2.3
      3.8 h) than vancomycin (0-1.3 h) against MRSA strain 1936. Arbekacin induced
      marked morphological changes at 0.5 x MIC and the changes remained for 2 h after
      removal of the agent. When exposed to 0.5 x MIC of vancomycin, no notable
      morphological change was observed in the treated cells. Since arbekacin has broad
      spectrum activity, these findings suggest that it may be a useful agent against
      MRSA infection, especially for polymicrobial MRSA infection with Gram-negative
      bacilli, such as Pseudomonas aeruginosa.

PMID- 9145821
TI  - Molecular typing of Enterococcus faecalis strains resistant to high levels of
      gentamicin and isolated in Romania.
AB  - Sixteen Enterococcus faecalis strains resistant to high levels of gentamicin, 15
      of which were isolated in the same year in a Romanian hospital, harboured
      conjugative gentamicin resistance (Gm(r)) plasmids ranging from 55 to 85
      kilobases. On the basis of restriction enzyme and DNA-DNA hybridization profiles
      of these plasmids, as well as of chromosomal SmaI macrorestriction and Tn916
      hybridization patterns, clonal relationship was established for seven strains
      whereas the other strains were considered to be independent. Nine and seven of
      the Gm(r) plasmids carried Tn4001-like and Tn4001-truncated structures,
      respectively; the latter structures were truncated in the right-hand flanking
      extremity of the element.

PMID- 9145820
TI  - In-vitro modelling of the bactericidal activity of teicoplanin versus
      flucloxacillin as used in surgical prophylaxis, against Staphylococcus aureus.
AB  - The bactericidal activities of teicoplanin and flucloxacillin in a 50:50 mixture
      of human serum and Iso-sensitest broth were compared in an in-vitro
      pharmacokinetic model, at serum concentrations present during surgical
      prophylaxis. The bactericidal activity of teicoplanin with and without serum was
      also compared. Six strains of Staphylococcus aureus were tested. The bactericidal
      rate of teicoplanin in serum was significantly lower than the rate in broth
      alone. However, there was no significant difference in the bactericidal rates in
      serum of teicoplanin compared with flucloxacillin, an antibiotic which is
      commonly used as prophylaxis for certain surgical procedures.

PMID- 9145822
TI  - Effect of combination therapy of rifampicin and azithromycin on TNF levels during
      a rat model of chronic osteomyelitis.
AB  - The purpose of the present study was to evaluate the combination of azithromycin
      and rifampicin on experimental chronic osteomyelitis due to Staphylococcus
      aureus. Alterations in bone bacterial titre, activity of tumour necrosis factor
      (TNF), a cytokine implicated in inflammation-induced bone pathology, and
      histopathological changes during infection and following antibiotic treatment
      were evaluated. Rats were infected with S. aureus by direct tibial inoculation
      and then randomized 56 days after infection to receive saline treatment or a
      combination of azithromycin and rifampicin (50 mg/kg po and 25 mg/kg sc
      respectively) once daily for 21 days. The combination of azithromycin and
      rifampicin was successful as determined by dramatic reduction in bone bacterial
      counts (approximately log 4 cfu), but regrowth of the organisms occurred
      suggesting that the duration of treatment was insufficient. TNF alpha mRNA and
      TNF activity were constantly elevated by approximately 20- and >200-fold,
      respectively, and remained elevated irrespective of antimicrobial treatment. Bone
      histology revealed extensive increase in bone turnover in both the infected and
      antibiotic treated bones with no difference being observed between the groups.
      This suggests that, in infected bone, the elevated TNF levels observed may be
      directly related to the bone pathology and both remain largely unchanged despite
      potent antibiotic therapy.

PMID- 9145823
TI  - Atypical pneumonia in the Nordic countries: aetiology and clinical results of a
      trial comparing fleroxacin and doxycycline. Nordic Atypical Pneumonia Study
      Group.
AB  - Community-aquired pneumonia caused by atypical bacteria or viruses was studied in
      a double-blind trial comparing fleroxacin 400 mg od and doxycycline 100 mg bd for
      10 days. The aetiology was confirmed in 258 of 411 cases (66%), of which 133 were
      caused by Mycoplasma spp., Chlamydia spp. or Legionella spp.; 30 patients had
      viral infection, nine had pneumococcal or Haemophilus influenzae infection and 93
      had mixed aetiology. In intention-to-treat analyses clinical response rates in
      fleroxacin-treated patients were 86% (157/182) and 75% (137/182) 2-8 days and 3-5
      weeks after therapy, respectively. Corresponding results with doxycycline were
      93% (177/191) and 85% (162/190), respectively. Differences between treatments
      seemed to be due to the lower activity of fleroxacin compared with doxycycline
      against mycoplasma and pneumococci. Drug-related adverse events were reported in
      39% of 204 fleroxacin patients and in 34% of 207 doxycycline patients. The null
      hypothesis that fleroxacin was <15% inferior to doxycycline was accepted at early
      follow-up but rejected at later review.

PMID- 9145825
TI  - An evaluation of the bactericidal activity of ampicillin/sulbactam,
      piperacillin/tazobactam, imipenem or nafcillin alone and in combination with
      vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) in time
      kill curves with infected fibrin clots.
AB  - The activity of piperacillin/tazobactam, ampicillin/sulbactam, imipenem and
      nafcillin alone and in combination with vancomycin was compared with vancomycin
      monotherapy against MRSA in test-tube time-kill studies and in infected fibrin
      clots. Bactericidal activity was achieved with all regimens except nafcillin
      monotherapy in test tubes but only with imipenem/vancomycin and
      nafcillin/vancomycin in fibrin clots infected with heterogeneous strains. No
      regimen was effective against the homogeneous strain. These agents may have
      potential as alternatives to vancomycin in selected infections.

PMID- 9145824
TI  - In-vitro and in-vivo activities of DW-116, a new fluoroquinolone.
AB  - DW-116 is a novel fluoroquinolone that was two- to four-fold more active than
      rufloxacin and less active than sparfloxacin, ciprofloxacin and ofloxacin against
      Gram-positive bacteria in vitro. Against Gram-positive and Gram-negative
      bacteria, the in-vivo activity of DW-116 was similar or slightly greater than
      that of rufloxacin and less than that of sparfloxacin, ciprofloxacin and
      ofloxacin. ED50 (50% effective dose) values for DW-116 did not correlate with in
      vitro MICs.

PMID- 9145826
TI  - Influence of gentamicin dosing interval on the efficacy of penicillin-containing
      regimens in experimental Enterococcus faecalis endocarditis.
AB  - The influence of the gentamicin dosing regimen was studied in experimental
      Enterococcus faecalis endocarditis. After inoculation, animals received
      penicillin, or penicillin plus once-daily gentamicin, or penicillin plus thrice
      daily gentamicin, or no treatment. After the treatment period, bacterial
      densities within the vegetations (mean +/- SEM) were 6.06 +/- 0.30, 5.42 +/-
      0.29, 4.98 +/- 0.10 and 9.97 +/- 0.16 log cfu/g for the four groups. All regimens
      produced significant reductions in bacterial density when compared with controls;
      penicillin plus thrice-daily gentamicin resulted in a significant difference from
      penicillin alone. Although once-daily regimens have proved effective in trials
      involving other organisms, such regimens do not appear to be so optimal for the
      treatment of enterococcal endocarditis.

PMID- 9145827
TI  - Effect of Khat chewing on the bioavailability of ampicillin and amoxycillin.
AB  - The study examined the effect of Khat chewing on ampicillin and amoxycillin
      bioavailability following the administration of a 500 mg single dose of each
      antibiotic at different times relative to Khat chewing. Using a urinary excretion
      method the bioavailabilities of ampicillin and amoxycillin were determined in
      eight healthy adult male Yemeni volunteers. The extent and rate of ampicillin
      bioavailability were reduced significantly by Khat chewing except when
      administered 2 h after the Khat chewing session. However, the bioavailability of
      amoxycillin was only significantly reduced when the antibiotic was taken midway
      through the Khat chewing session. It was concluded that the two antibiotics,
      particularly ampicillin, should be taken 2 h after Khat chewing.

PMID- 9145829
TI  - Health care resource utilization and antimicrobial use in elderly patients with
      community-acquired lower respiratory tract infection who develop Clostridium
      difficile-associated diarrhoea.
AB  - We conducted a prospective observational study on the medical management and
      health service resource utilization associated with the hospital care of patients
      with community-acquired lower respiratory tract infection. Between January 1994
      and June 1995, 28 such patients developed Clostridium difficile-associated
      diarrhoea; these 28 patients were matched with 56 age-matched patients, who were
      used as a control group in a comparative study. Progress during the first week
      after admission was similar as measured by fever days and pathology or radiology
      use. The use of iv cephalosporins (g/day) during the first week was greater in
      the group who developed C. difficile-associated diarrhoea than in controls. The
      length of hospital stay was 36.4 +/- 21.6 days in patients with C. difficile
      associated diarrhoea compared with 19.8 +/- 13.3 days in controls. Cases also
      required more pathological and radiological tests and greater use of
      antimicrobials and other drugs; however, if pathology and radiology use was
      calculated per day of patient stay there was no difference between the two
      groups. When antimicrobial use was compared, controlling for the time taken until
      found to be C. difficile toxin positive, patients with C. difficile infection
      received more iv cefuroxime as well as more total cephalosporins, beta-lactams
      and macrolides measured in g/day. Interestingly, in this study we could not show
      an increased mortality associated with C. difficile diarrhoea despite obvious
      evidence of morbidity. The development of C. difficile-associated diarrhoea
      substantially increases health care resource utilization for individual patients
      who are admitted to hospital with lower respiratory tract infection.

PMID- 9145828
TI  - Indications for antibiotic use in ICU patients: a one-year prospective
      surveillance.
AB  - The high prevalence of nosocomial infections in critically ill ICU patients is
      associated with high antibiotic consumption. Besides its economic impact, there
      is the constant threat of selection and induction of antibiotic resistance.
      Surveillance studies recording the incidence of infections, antibiotic use, and
      antimicrobial susceptibilities of pathogens supply vital information regarding
      infection control and prevention of antibiotic resistance. In order to analyse
      antibiotic consumption we recorded antibiotic use in a general ICU during one
      year by categorizing the indications for antibiotic use into three groups; (i)
      prophylaxis; (ii) therapy for a bacteriologically proven infection (BPI); (iii)
      therapy for a non-bacteriologically proven infection (non-BPI). Bronchoscopic
      techniques were used to diagnose pneumonia. In practice, BPI must be treated, but
      a proportion of antibiotics prescribed for non-BPI may be unnecessary. The
      subdivision in BPI and non-BPI may help to identify these cases. In all, 515
      patients were admitted to ICU and 36% of these had at least one infection. Of all
      infections, 53% were ICU-acquired and 99% of these occurred in intubated
      patients. Antibiotics were prescribed in 61% of admissions. Of all antibiotics
      prescribed for therapy, 49% were for respiratory tract infections, 19% for
      abdominal infections and 13% for sepsis eci. Categorized by indication, 59% of
      all antibiotic prescriptions were for BPI, 28% for non-BPI and 13% for
      prophylaxis. A theoretical reduction of 25% in the number of non-BPI
      prescriptions would result only in a 7% decrease of total antibiotic use. We
      conclude that almost all antibiotics prescribed were for intubated patients and
      for BPI. Respiratory infections were the single most common infection and
      accounted for 49% of all antibiotics used. Therefore, in our setting, prevention
      of respiratory tract infections is probably the most effective mode to reduce
      antibiotic use.

PMID- 9145830
TI  - Over-the-counter availability of antimicrobial agents, self-medication and
      patterns of resistance in Karachi, Pakistan.
AB  - To determine whether the free availability of antimicrobial agents leads to
      misuse through self-medication, a house-to-house semi-structured interview was
      held in three different socio-economic areas of Karachi, Pakistan. Of the 2348
      households visited, 1342 (57%) participated; this included 9209 individuals.
      Three hundred and twenty-two (3.5%) had used one or more antimicrobial in the
      previous 4 weeks, equivalent to 43 agents per 1000 persons per month. The most
      frequently used agents were amoxycillin (16.7%), co-trimoxazole (15.7%),
      erythromycin (10.9%), ampicillin/cloxacillin (Ampiclox, 9.1%) and metronidazole
      (4.5%). Of these, 91.4% were prescribed by a physician, 2.3% were advised by a
      chemist and 6.3% were used as self-medication. Self-medication increased with
      socio-economic status. High levels of resistance were found to ampicillin, co
      trimoxazole, chloramphenicol and erythromycin. If these high resistance levels
      are related to the high frequency of antimicrobial use, over-the-counter
      availability cannot be held responsible. Education of the medical profession
      seems to be the single most important tool to control misuse of antimicrobial
      agents. Innovative approaches for continuous medical education are urgently
      needed.

PMID- 9145831
TI  - Is Escherichia coli ATCC 25922 useful for monitoring broth microdilution tests of
      fluoroquinolones?

PMID- 9145832
TI  - Etest evaluation of enterobacteriaceae with reduced susceptibility to
      ciprofloxacin.

PMID- 9145833
TI  - Intracellular activity of trovafloxacin (CP-99,219) against Enterococcus faecium.

PMID- 9145834
TI  - Neonatal meningitis due to multi-resistant Listeria monocytogenes.

PMID- 9145835
TI  - Decreasing trend of multiresistant Salmonella typhi in Bangladesh.

PMID- 9145836
TI  - Intravenous desensitization to ceftazidime in cystic fibrosis patients.

PMID- 9145837
TI  - Corticosteroids in pneumococcal meningitis.

PMID- 9145838
TI  - Comparative in vitro antimicrobial susceptibilities of nosocomial isolates of
      Acinetobacter baumannii and synergistic activities of nine antimicrobial
      combinations.
AB  - The in vitro susceptibilities of 69 nosocomial Acinetobacter isolates were
      determined by the broth microdilution method. Fourteen (20%) isolates were
      resistant to at least two aminoglycosides and two extended-spectrum penicillins.
      Nine antimicrobial combinations were then tested for synergy against these 14
      isolates by checkerboard titration: imipenem with ciprofloxacin, amikacin, and
      tobramycin and ampicillin-sulbactam, piperacillin-tazobactam, and ticarcillin
      clavulanate with amikacin and tobramycin. Synergy was detected with one or more
      antimicrobial combinations against 9 of 14 (64%) isolates, partial synergy was
      detected with one or more combinations against all 14 isolates, and an additive
      effect alone was observed with two different combinations against two isolates.
      No antagonism was detected with any combination. Imipenem plus either amikacin or
      tobramycin resulted in a synergistic or partial synergistic response against all
      14 isolates. Specific combinations showing synergy against A. baumannii isolates
      were imipenem with tobramycin (four isolates), imipenem with amikacin (three
      isolates), ampicillin-sulbactam with tobramycin (six isolates), ampicillin
      sulbactam with amikacin (three isolates), and ticarcillin-clavulanate with
      tobramycin (one isolate). Genotyping by randomly amplified polymorphic DNA
      analysis showed that 9 of the 14 isolates were of one strain, 4 isolates were of
      a second strain, and the remaining isolate was of a different strain. Eight of 14
      (57%) patients infected with resistant A. baumannii isolates died. Only 3 of 14
      patients had received a therapeutic regimen which was tested for synergy.
      Clinical studies are needed to determine the significance of these findings.

PMID- 9145839
TI  - Behavior of amphotericin B lipid complex in plasma in vitro and in the
      circulation of rats.
AB  - Amphotericin B lipid complex (ABLC) shows reduced toxicity relative to that of
      amphotericin B deoxycholate (AmB-d) while maintaining antifungal activity. Rat
      blood or plasma was spiked with ABLC in vitro. Released amphotericin B was
      separated from the parent material by centrifugation. At early times (0 to 15
      min) most (approximately 90%) of the amphotericin B was complexed. The amount of
      released amphotericin B increased gradually in a time- and temperature-dependent
      fashion. The released amphotericin B was associated with plasma lipoprotein and
      nonlipoprotein proteins. The area under the concentration-time curve from 0 to 24
      h for total amphotericin B in whole blood of rats given a single intravenous
      bolus dose of 1 mg of ABLC per kg of body weight was fourfold lower than that in
      rats given 1 mg of AmB-d per kg. The complexed amphotericin B was rapidly removed
      from the circulation and was distributed to the tissues in these rats. Other rats
      were treated intravenously with ABLC (10 mg/kg/day) or AmB-d (0.5 mg/kg/day)
      daily for 15 days. Blood was collected at 15 and 180 min after administration of
      the last dose. The total levels of amphotericin B in the blood of the group given
      ABLC were about three to five times those in the group given AmB-d, and the
      concentration of released, protein-bound amphotericin B in the plasma of the
      group given ABLC was about one to two times that observed for the group given AmB
      d, despite the 20-fold difference in dose. The relative protein distribution of
      amphotericin B in plasma was similar after ABLC or AmB-d administration under
      these steady-state conditions in vivo. The rapid uptake of complexed amphotericin
      B by tissues and the very low levels of circulating protein-bound amphotericin B
      in plasma after the administration of ABLC may explain, in part, the reduced
      toxicity and enhanced therapeutic index of this preparation.

PMID- 9145840
TI  - Activity of trovafloxacin in combination with other drugs for treatment of acute
      murine toxoplasmosis.
AB  - Current therapy for toxoplasmosis with a synergistic combination of pyrimethamine
      plus sulfadiazine or pyrimethamine plus clindamycin is not always efficacious and
      is frequently discontinued due to intolerable toxic effects in immunocompromised
      individuals, particularly those with AIDS. Trovafloxacin, a new fluoroquinolone
      with potent activity against Toxoplasma gondii, was examined for potential
      synergistic activity when combined with other drugs used for treatment of human
      toxoplasmosis. Combinations of trovafloxacin with clarithromycin, pyrimethamine,
      or sulfadiazine demonstrated significantly enhanced activities compared to those
      observed with each drug alone. Our results suggest that combinations of
      trovafloxacin and other anti-toxoplasma drugs should be further explored for
      treatment of toxoplasmosis in humans.

PMID- 9145841
TI  - Multiple-dose pharmacokinetics of ritonavir in human immunodeficiency virus
      infected subjects.
AB  - The multiple-dose pharmacokinetics of ritonavir were investigated in four groups
      of human immunodeficiency virus-positive male subjects (with 16 subjects per
      group) under nonfasting conditions; a 3:1 ritonavir:placebo ratio was used.
      Ritonavir was given at 200 (group I), 300 (group II), 400 (group III), or 500
      (group IV) mg every 12 h for 2 weeks. The multiple-dose pharmacokinetics of
      ritonavir were moderately dose dependent, with the clearance for group IV (6.8 +/
      2.7 liters/h) being an average of 32% lower than that for group I (10.0 +/- 3.2
      liters/h). First-pass metabolism should be minimal for ritonavir. The functional
      half-life, estimated from peak and trough concentrations, were similar among the
      dosage groups, averaging 3.1 and 5.7 h after the morning and evening doses,
      respectively. The area under the concentration-time curve at 24 h (AUC24) and
      apparent terminal-phase elimination rate constant remained relatively time
      invariant, but predose concentrations decreased 30 to 70% over time.
      Concentration-dependent autoinduction is the most likely mechanism for the time
      dependent pharmacokinetics. The Km and initial maximum rate of metabolism (Vmax)
      values estimated from population pharmacokinetic modeling (nonlinear mixed
      effects models) were 3.43 microg/ml and 46.9 mg/h, respectively. The group IV
      Vmax increased to 68 mg/h after 2 weeks. The maximum concentration of ritonavir
      in serum (Cmax) and AUC after the evening doses were an average of 30 to 40%
      lower than the values after the morning doses, while the concentration at 12 h
      was an average of 32% lower than the predose concentration, probably due to
      protracted absorption. Less than 2% of the dose was eliminated unchanged in the
      urine. Triglyceride levels increased from the levels at the baseline, and the
      levels were correlated with baseline triglyceride levels and AUC, Cmax, or
      predose concentrations.

PMID- 9145842
TI  - Increased expression of fibronectin-binding proteins by fluoroquinolone-resistant
      Staphylococcus aureus exposed to subinhibitory levels of ciprofloxacin.
AB  - Bacterial adhesion, which plays an important role in Staphylococcus aureus
      colonization and infection, may be altered by the presence of antibiotics or/and
      antibiotic resistance determinants. This study evaluated the effect of
      fluoroquinolone resistance determinants on S. aureus adhesion to solid-phase
      fibronectin, which is specifically mediated by two surface-located fibronectin
      binding proteins. Five isogenic mutants, derived from strain NCTC 8325 and
      expressing various levels of quinolone resistance, were tested in an in vitro
      bacterial adhesion assay with polymethylmethacrylate coverslips coated with
      increasing amounts of fibronectin. These strains contained single or combined
      mutations in the three major loci contributing to fluoroquinolone resistance,
      namely, grlA, gyrA, and flqB, which code for altered topoisomerase IV, DNA
      gyrase, and increased norA-mediated efflux of fluoroquinolones, respectively.
      Adhesion characteristics of the different quinolone-resistant mutants grown in
      the absence of fluoroquinolone showed only minor differences from those of
      parental strains. However, more important changes in adhesion were exhibited by
      mutants highly resistant to quinolones following their exponential growth in the
      presence of one-quarter MIC of ciprofloxacin. Increased bacterial adhesion of the
      highly quinolone-resistant mutants, which contained combined mutations in grlA
      and gyrA, was associated with and explained by the overexpression of their
      fibronectin-binding proteins as assessed by Western ligand affinity blotting.
      These findings contradict the notion that subinhibitory concentrations of
      antibiotics generally decrease the expression of virulence factors by S. aureus.
      Perhaps the increased adhesion of S. aureus strains highly resistant to
      fluoroquinolones contributes in part to that emergence in clinical settings.

PMID- 9145843
TI  - Pharmacokinetics of oral fluconazole when used for prophylaxis in bone marrow
      transplant recipients.
AB  - The pharmacokinetics of fluconazole was investigated in 20 bone marrow transplant
      patients following oral administration of 200 mg of this drug. Blood samples were
      collected from each patient at different time intervals within 48 h after the
      first dose, and fluconazole was measured in plasma by high-performance liquid
      chromatography with UV detection. Urine was collected from 14 of these patients
      and analyzed similarly. The plasma concentration-time data exhibited the
      characteristics of the one-compartment model with first-order absorption quite
      well. The means +/- standard deviations of half-lives for absorption and
      elimination, peak concentration, time to peak, mean residence time, apparent
      volumes of distribution, area under the curve, and apparent oral clearance
      observed in these patients were 2.84 +/- 1.34 h, 19.94 +/- 18.7 h, 4.45 +/- 1.86
      microg/ml, 8.34 +/- 5.97 h, 39.57 +/- 20.5 h, 0.874 +/- 0.48 liter/kg, 156.0 +/-
      60.6 microg x h/ml, and 0.0256 +/- 0.0138 liter/h x kg, respectively. The amount
      of fluconazole excreted in urine in 24 h was 67.1 +/- 83 mg, which represents
      33.55% +/- 41.6% of the dose administered. Patients who developed hemorrhagic
      cystitis excreted significantly (P < or = 0.0094) more fluconazole in 24 h than
      did those who did not.

PMID- 9145844
TI  - Modulation of the metabolism of beta-L-(-)-2',3'-dideoxy-3'-thiacytidine by
      thymidine, fludarabine, and nitrobenzylthioinosine.
AB  - beta-L-(-)-2',3'-Dideoxy-3'-thiacytidine (3TC) is a cytosine nucleoside analog
      that potently inhibits the replication of human and duck hepatitis B viruses and
      human immunodeficiency virus through the activity of its 5'-triphosphate ester
      metabolite. The present study examined the intracellular decay of 3TC 5'
      phosphates and tested strategies for modulating the cellular content of those
      nucleotides in primary cultures of duck hepatocytes and in human hepatoma 2.2.15
      cells and CCRF-CEM T lymphoblasts. Inhibition by deoxycytidine of the 5'
      phosphorylation of 3TC in duck hepatocytes confirmed that, as in mammalian cells,
      deoxycytidine kinase catalyzed 3TC activation. The 5'-mono, 5'-di-, and 5'
      triphosphates of 3TC underwent monoexponential elimination from duck hepatocytes
      and 2.2.15 cells (half-lives, 3.6 to 8.0 h). Thymidine and fludarabine, which are
      agents that enhance the activity of deoxycytidine kinase, were tested in
      strategies for increasing the cellular content of 3TC 5'-phosphates. Coordinate
      treatment of cells with 3TC and thymidine (50 microM) increased the content of
      3TC 5'-monophosphate in duck hepatocytes and the content of 3TC 5'-di- and 5'
      triphosphates in 2.2.15 cells, but enhancement of 3TC 5'-phosphate levels in CCRF
      CEM cells required a higher thymidine concentration (100 microM). Fludarabine (5
      microM) did not affect the contents of 3TC 5'-di- and 5'-triphosphates in duck
      hepatocytes, but modestly increased the contents of those nucleotides in 2.2.15
      cells and CCRF-CEM cells. Nitrobenzylthioinosine (NBMPR), an inhibitor of the es
      facilitated diffusion nucleoside transporter, reduced the level of entry of 3TC
      into 2.2.15 cells and abolished inward fluxes of thymidine, adenosine, and
      deoxycytidine. In 2.2.15 cells and CCRF-CEM cells, NBMPR reduced the formation of
      3TC 5'-di- and 5'-triphosphates and reversed the thymidine- and fludarabine
      induced increases in the formation of those nucleotides. NBMPR protected against
      the cytotoxicity of 3TC in CCRF-CEM cells, whereas thymidine potentiated that
      toxicity, apparently by enhancing the formation of 3TC 5'-triphosphate. Taken
      together, these results indicate that deoxycytidine kinase and the es nucleoside
      transporter are targets for manipulation of the metabolism and activity of 3TC.

PMID- 9145845
TI  - Metabolism of rifabutin and its 25-desacetyl metabolite, LM565, by human liver
      microsomes and recombinant human cytochrome P-450 3A4: relevance to clinical
      interaction with fluconazole.
AB  - Rifabutin and fluconazole are often given concomitantly as therapy to prevent
      opportunistic infections in individuals infected with the human immunodeficiency
      virus. Recent reports have shown increased levels of rifabutin and its 25
      desacetyl metabolite, LM565, in plasma when rifabutin is administered with
      fluconazole. Since fluconazole is known to inhibit microsomal enzymes, this study
      was undertaken to determine if this rifabutin-fluconazole interaction was due to
      an inhibition of human hepatic enzymes. The metabolism of both rifabutin and
      LM565 was evaluated in human liver microsomes and recombinant human cytochrome P
      450 (CYP) 3A4 in the presence of fluconazole and other probe drugs known to
      inhibit CYP groups 1A2, 2C9, 2D6, 2E1, and 3A. The concentrations of rifabutin (1
      microg/ml), LM565 (1 microg/ml), and fluconazole (10 and 100 microg/ml) used were
      equal to those observed in plasma after the administration of rifabutin and
      fluconazole at clinically relevant doses. High-performance liquid chromatography
      was used to assess the metabolism of rifabutin and LM565. Rifabutin was readily
      metabolized to LM565 by human microsomes, but the reaction was independent of
      NADPH and was not affected by the P-450 inhibitors. No rifabutin metabolism by
      recombinant CYP 3A4 was found to occur. LM565 was also metabolized by human
      microsomes to two products, but metabolism was dependent on NADPH and was
      affected by certain P-450 inhibitors. In addition, LM565 was readily metabolized
      by the recombinant CYP 3A4 to the same two products found with its metabolism by
      human microsomes. Therefore, rifabutin is metabolized by human microsomes but not
      via cytochrome P-450 enzymes, whereas LM565 is metabolized by CYP 3A4.

PMID- 9145846
TI  - Suspicion of quinolone active metabolite following discrepancy between predicted
      and experimental urine bactericidal activities.
AB  - The prediction of urine antibacterial activity from pharmacological and
      microbiological parameters was assessed by using experimental urine levels and
      urine bactericidal titers determined up to 72 h after a 400-mg single dose of two
      quinolones in a phase I study. The area under the bactericidal curve (AUBC) was
      accurately predicted for norfloxacin but significantly (P < 0.001) underestimated
      for rufloxacin (actual value was four times higher than the predicted value
      against Escherichia coli and two times higher against Staphylococcus aureus). In
      vitro susceptibility differences between the two strains predicted the ex vivo
      AUBC differences for norfloxacin but not for rufloxacin, where ex vivo
      differences were greater than expected. Urine bactericidal titers for up to 72 h
      were accurately predicted for norfloxacin against E. coli and S. aureus and for
      rufloxacin against S. aureus, but experimental activity for up to 48 h was four
      times higher (P < 0.001) than the predicted activity for rufloxacin against E.
      coli. In the case of norfloxacin, the duration of adequate urine antibacterial
      activity against S. aureus was overestimated. Inaccurate estimations of ex vivo
      antibacterial activity of a suspected active metabolite (as with rufloxacin) when
      an adequate cutoff is not established may have dosing implications.

PMID- 9145847
TI  - Influence of inducible cross-resistance to macrolides, lincosamides, and
      streptogramin B-type antibiotics in Enterococcus faecium on activity of
      quinupristin-dalfopristin in vitro and in rabbits with experimental endocarditis.
AB  - The influence of inducible cross-resistance to macrolides, lincosamides, and
      streptogramin B (MLS(B)) type antibiotics (inducible MLS(B) phenotype) on the
      activity of quinupristin-dalfopristin was investigated against Enterococcus
      faecium in vitro and in rabbits with experimental endocarditis. In vitro,
      quinupristin-dalfopristin displayed bacteriostatic and bactericidal activities
      against a MLS(B)-susceptible strain similar to those against two strains with the
      inducible MLS(B) phenotype. In addition, induction of the two MLS(B)-resistant
      strains with quinupristin (0.016 to 1 microg/ml) or quinupristin-dalfopristin
      (0.08 to 0.25 microg/ml) increased the MICs of quinupristin from 8 microg/ml to
      32 to > 128 microg/ml, but did not modify the MIC of dalfopristin (2 microg/ml)
      or quinupristin-dalfopristin (0.5 microg/ml). In a rabbit endocarditis model,
      quinupristin-dalfopristin was as active as amoxicillin against the MLS(B)
      susceptible E. faecium strain. In contrast, the activity of quinupristin
      dalfopristin was significantly decreased in animals infected with either of the
      two inducible MLS(B)-resistant strains (P < 0.05), although no mutants resistant
      to quinupristin-dalfopristin were detected. Against the clinical strain with the
      inducible MLS(B) phenotype, quinupristin-dalfopristin was not effective and was
      less active than amoxicillin (P < 0.001); however, the activity of the
      combination of amoxicillin and dalfopristin-quinupristin was superior to that of
      amoxicillin (P < 0.01). The different impact of the inducible MLS(B) phenotype in
      E. faecium on the activity of quinupristin-dalfopristin in vitro and in
      experimental endocarditis may be related to the reduced diffusion of dalfopristin
      compared with that of quinupristin into cardiac vegetations that we previously
      reported. This result emphasizes the importance of the constant presence of
      dalfopristin at the site of infection to ensure synergism with quinupristin.

PMID- 9145849
TI  - Survey and molecular genetics of SHV beta-lactamases in Enterobacteriaceae in
      Switzerland: two novel enzymes, SHV-11 and SHV-12.
AB  - Sixty isolates of Enterobacteriaceae resistant to beta-lactam antibiotics were
      collected over a period of 2 years in Switzerland and screened by hybridization
      for the carriage of SHV genes. Thirty-four positive strains were found, and their
      SHV genes were amplified and sequenced. SHV extended-spectrum beta-lactamases
      (ESBLs) were found: 13 strains contained SHV-2a, 12 harbored SHV-2, and SHV-5 was
      found twice. Four strains were shown to contain SHV-1. In addition, we report two
      new SHV variants, termed SHV-11 (non-ESBL) and SHV-12 (ESBL). In spite of the
      carriage of SHV ESBLs, many strains showed only low resistance to one or more
      third-generation cephalosporins. In addition, 26 did not transfer the blaSHV gene
      in mating experiments.

PMID- 9145848
TI  - A mutation in the D,D-carboxypeptidase penicillin-binding protein 3 of
      Streptococcus pneumoniae contributes to cefotaxime resistance of the laboratory
      mutant C604.
AB  - Cefotaxime resistance in laboratory mutant C604 of Streptococcus pneumoniae, for
      which the MIC is 1.5 microg/ml, is independent of alterations in high-molecular
      mass penicillin-binding protein (PBP) 1a. Instead, a point mutation in PBP 3, the
      D,D-carboxypeptidase of this organism, caused a reduced affinity for penicillin
      and contributed to the decreased susceptibility. The mutation Thr-242 to Ile was
      located directly adjacent to the triad Lys-239-Thr-Gly, a position known to be
      important for beta-lactam interaction with high-molecular-mass PBPs and beta
      lactamases. This mutation was absent in the PBP 3's of four genetically distinct
      clinical isolates resistant to high levels of penicillin. None of the pbp3 genes
      had a mosaic structure, but in three cases there was evidence for a site-specific
      recombination event within a BOX element immediately downstream of pbp3.

PMID- 9145850
TI  - Comparison of the postantibiotic and postantibiotic sub-MIC effects of
      levofloxacin and ciprofloxacin on Staphylococcus aureus and Streptococcus
      pneumoniae.
AB  - The postantibiotic subminimum inhibitory concentration effect (PA SME) may
      simulate in vivo drug exposure more accurately than the postantibiotic effect
      (PAE) since subinhibitory concentrations of drug persist between antibiotic
      dosings. In this study, we compared the PAEs and PA SMEs of levofloxacin and
      ciprofloxacin for clinical isolates of fluoroquinolone-susceptible Staphylococcus
      aureus and Streptococcus pneumoniae. At two times the MIC, PAEs of levofloxacin
      were an average of 0.6 h longer than the PAEs obtained for ciprofloxacin for
      methicillin-susceptible and methicillin-resistant S. aureus strains. The PAEs of
      levofloxacin and ciprofloxacin ranged from 1.8 to 3.1 and 1.1 to 2.4 h,
      respectively. Continued exposure of the methicillin-resistant strain to 1/16,
      1/8, and 1/4 the MIC resulted in PA SMEs of 6.5, 15.3, and >22.3 h, respectively,
      for levofloxacin and 3.8, 8.0, and 12.3 h, respectively, for ciprofloxacin. For
      isolates of S. pneumoniae, at two times the MIC of both fluoroquinolones, the
      average PAEs of levofloxacin and ciprofloxacin were equivalent: 1.3 h for the
      penicillin-susceptible isolate and 0.6 h for the penicillin-resistant isolate.
      Continued exposure of the penicillin-susceptible S. pneumoniae strain to 1/16,
      1/8, and 1/4 the MIC resulted in average PA SMEs of 1.0, 1.4, and 2.8 h,
      respectively, for levofloxacin and 1.8, 2.0, and 2.5 h, respectively, for
      ciprofloxacin. Continued exposure of penicillin-resistant S. pneumoniae to 1/16,
      1/8, and 1/4 the MIC of the same fluoroquinolones resulted in average PA SMEs of
      0.6, 1.1, and 2.9 h, respectively, for levofloxacin and 0.6, 1.1, and 1.5 h,
      respectively, for ciprofloxacin. The PA SMEs observed demonstrate the superior
      activity of levofloxacin against methicillin-susceptible or methicillin-resistant
      S. aureus. Although PAEs were similar for the penicillin-susceptible and
      penicillin-resistant S. pneumoniae strains, the PA SME of levofloxacin at one
      fourth the MIC was longer for penicillin-resistant S. pneumoniae.

PMID- 9145851
TI  - Overexpression and characterization of the chromosomal aminoglycoside 6'-N
      acetyltransferase from Enterococcus faecium.
AB  - The chromosomal gene aac(6')-Ii, encoding an aminoglycoside 6'-N
      acetyltransferase in Enterococcus faecium, renders this organism resistant to
      moderate levels of many aminoglycoside antibiotics. The ubiquitous presence of
      aac(6')-Ii in E. faecium complicates the selection of antibiotics for treatment
      of infections caused by this organism. In view of the importance of this enzyme,
      we have initiated studies to gain an understanding of its molecular mechanism of
      acetyl transfer. The AAC(6')-Ii enzyme was overexpressed in Escherichia coli and
      purified in a simple three-step procedure which yields 55 mg of pure dimeric
      protein per liter of cell culture. Steady-state kinetic analyses revealed a broad
      substrate specificity and demonstrated that acetylation occurs exclusively at
      position N-6'. k(cat)/Km values were on the order of 10(4) M(-1) s(-1), which is
      relatively low compared to other aminoglycoside-modifying enzymes. In addition,
      MIC values were positively correlated with k(cat), the rate when the enzyme is
      saturated with the aminoglycoside substrate, and not with k(cat)/Km, the rate at
      low aminoglycoside (sub-Km) concentrations. These results describe an enzyme
      which is not optimally evolved for aminoglycoside inactivation and suggest that
      this chromosomally encoded enzyme may have an alternate physiological function.

PMID- 9145852
TI  - Ginseng treatment reduces bacterial load and lung pathology in chronic
      Pseudomonas aeruginosa pneumonia in rats.
AB  - The predominant pathogen in patients with cystic fibrosis (CF) is Pseudomonas
      aeruginosa, which results in a chronic lung infection associated with progressive
      pulmonary insufficiency. In a rat model of chronic P. aeruginosa pneumonia
      mimicking that in patients with CF, we studied whether the inflammation and
      antibody responses could be changed by treatment with the Chinese herbal medicine
      ginseng. An aqueous extract of ginseng was injected subcutaneously, and cortisone
      and saline were used as controls. Two weeks after challenge with P. aeruginosa,
      the ginseng-treated group showed a significantly improved bacterial clearance
      from the lungs (P < 0.04), less severe lung pathology (P = 0.05), lower lung
      abscess incidence (P < 0.01), and fewer mast cell numbers in the lung foci (P <
      0.005). Furthermore, lower total immunoglobulin G (IgG) levels (P < 0.01) and
      higher IgG2a levels (P < 0.025) in serum against P. aeruginosa sonicate and a
      shift from an acute type to a chronic type of lung inflammation compared to those
      in the control and cortisone-treated groups were observed. These findings
      indicate that ginseng treatment of an experimental P. aeruginosa pneumonia in
      rats promotes a cellular response resembling a TH1-like response. On the basis of
      these results it is suggested that ginseng may have the potential to be a
      promising natural medicine, in conjunction with other forms of treatment, for CF
      patients with chronic P. aeruginosa lung infection.

PMID- 9145853
TI  - Antiviral properties of palinavir, a potent inhibitor of the human
      immunodeficiency virus type 1 protease.
AB  - Palinavir is a potent inhibitor of the human immunodeficiency virus type 1 (HIV
      1) and type 2 (HIV-2) proteases. Replication of laboratory strains (HIV-1, HIV-2,
      and simian immunodeficiency virus) and HIV-1 clinical isolates is inhibited by
      palinavir with 50% effective concentrations ranging from 0.5 to 30 nM. The
      average cytotoxic concentration of palinavir (35 microM) in the various target
      cells indicates a favorable therapeutic index. Potent antiviral activity is
      retained with increased doses of virus and with clinical isolates resistant to
      zidovudine (AZT), didanosine (ddI), or nevirapine. Combinations of palinavir with
      either AZT, ddI, or nevirapine demonstrate synergy or additivity in the
      inhibition of HIV-1 replication. Palinavir retains anti-HIV-1 activity when
      administered postinfection until times subsequent to the reverse transcription
      step. In chronically infected CR-10 cells, palinavir blocks Gag precursor
      polyprotein processing completely, reducing greater than 99% of infectious
      particle production. The results indicate that the antiviral activity of
      palinavir is specific to inhibition of the viral protease and occurs at a late
      stage in the replicative cycle of HIV-1. On the basis of the potent in vitro
      activity, low-level cytotoxicity, and other data, palinavir was selected for in
      depth preclinical evaluation.

PMID- 9145854
TI  - Axenically cultured amastigote forms as an in vitro model for investigation of
      antileishmanial agents.
AB  - Using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide microassay,
      previously described as a means of quantifying Leishmania amazonensis in vitro at
      the amastigote stage (D. Sereno and J. L. Lemesre, Parisitol. Res., in press), we
      have compared the activities of seven drugs, including those currently used to
      treat leishmaniasis, against axenically grown amastigote and promastigote forms
      of three Leishmania species (L. amazonensis, L. mexicana, and L. infantum,
      responsible for diffuse cutaneous, cutaneous, and visceral leishmaniasis,
      respectively). The ability of axenically cultured amastigote organisms to be used
      in an investigation of antileishmanial agents was first evaluated. We have
      confirmed the toxicities of sodium stibogluconate (Pentostam), pentamidine, and
      amphotericin B to active and dividing populations of axenically cultured
      amastigotes. The toxicity of potassium antimonyl tartrate trihydrate, which is
      generally higher than that of Pentostam, seemed to indicate that pentavalent
      antimony can be metabolized in vivo to compounds, possibly trivalent in nature,
      which are more active against the amastigote organisms. When the drug
      susceptibilities of parasites at both stages were compared, great variations were
      found for all the drugs studied. These major differences, which show the specific
      chemosusceptibility of the parasite at the mammalian stage, demonstrate the
      potential of using cultured amastigotes instead of promastigotes in a drug
      screening procedure for early detection. This in vitro model may help in the
      isolation of active compounds, particularly those with low-grade activities,
      against the mammalian stage of the parasite.

PMID- 9145855
TI  - Topotecan inhibits human immunodeficiency virus type 1 infection through a
      topoisomerase-independent mechanism in a cell line with altered topoisomerase I.
AB  - Topotecan (TPT), a known inhibitor of topoisomerase I, has previously been shown
      to inhibit the replication of several viruses. The mechanism of inhibition was
      proposed to be the inhibition of topoisomerase I. We report that TPT decreased
      replication of human immunodeficiency virus type 1 (HIV-1) in CPT-K5, a cell line
      with a topoisomerase I mutation. TPT inhibited production of HIV-1 RNA and p24 in
      CPT-K5 and wild-type cells equally effectively. The antiviral effects of TPT were
      observed not only in the topoisomerase-mutated CPT-K5 line but also in peripheral
      blood mononuclear cells (PBMC) acutely infected with clinical isolates and in
      OM10.1 cells latently infected with HIV and activated by tumor necrosis factor
      alpha. Little toxicity from TPT was noted in HIV-1-infected PBMC and in CPT-K5
      and OM10.1 cells as measured by cell growth and proliferation assays. These
      observations suggest that TPT targets factors in virus replication other than
      cellular topoisomerase I and inhibits cytokine-mediated activation in latently
      infected cells by means other than cytotoxicity. These results suggest a
      potential for TPT and for other camptothecins in anti-HIV therapy alone and in
      combination with other antiretroviral drugs.

PMID- 9145856
TI  - Pharmacokinetics of intramuscularly administered aminosidine in healthy subjects.
AB  - Aminosidine is an older, broad-spectrum aminoglycoside antibiotic that has been
      shown to be effective in in vitro and animal models against multiple-drug
      resistant tuberculosis and the Mycobacterium avium complex. The objective of this
      randomized, parallel trial was to characterize the single-dose pharmacokinetics
      of aminosidine sulfate in healthy subjects (eight males, eight females). Sixteen
      adults (mean [+/- standard deviation] age, 27.6 +/- 5.6 years) were randomly
      allocated to receive a single, intramuscular aminosidine sulfate injection at a
      dose of 12 or 15 mg/kg of body weight. Serial plasma and urine samples were
      collected over a 24-h period and used to determine aminosidine concentrations by
      high-performance liquid chromatographic assay. A one-compartment model with first
      order input, first-order output, and a lag time (Tlag) and with a weighting
      factor of 1/y2 best described the data. Compartmental and noncompartmental
      pharmacokinetic parameters were estimated with the microcomputer program
      WinNonlin. One subject was not included (15-mg/kg group) because of the lack of
      sampling time data. On average, subjects attained peak concentrations of 22.4 +/-
      3.2 microg/ml at 1.34 +/- 0.45 h. All subjects had plasma aminosidine
      concentrations below 2 microg/ml at 12 h, and all but two subjects (one in each
      dosing group) had undetectable plasma aminosidine concentrations at 24 h. The
      dose-adjusted area under the concentration-time curve from 0 h to infinity of
      aminosidine was identical for the 12- and 15-mg/kg groups (9.29 +/- 1.5 versus
      9.29 +/- 2.2 microg x h/ml per mg/kg; P = 0.998). Similarly, no significant
      differences (P > 0.05) were observed between dosing groups for peak aminosidine
      concentration in plasma, time to peak aminosidine concentration in plasma, Tlag,
      apparent clearance, renal clearance, elimination rate constant, and elimination
      half-life. A significant difference was observed for the volume of distribution
      (0.35 versus 0.41 liters/kg; P = 0.037) between the 12 and 15 mg/kg dosing
      groups. Now that comparable pharmacokinetic profiles between dosing groups have
      been demonstrated, therapeutic equivalency testing via in vitro pharmacokinetic
      and pharmacodynamic modelling and randomized clinical trials in humans should be
      conducted.

PMID- 9145857
TI  - Kinetics of piperacillin and tazobactam in ventricular cerebrospinal fluid of
      hydrocephalic patients.
AB  - Its broad antibacterial spectrum qualifies the combination of piperacillin and
      tazobactam for therapy of nosocomial bacterial central nervous system (CNS)
      infections. Since these infections sometimes are accompanied by only minor
      dysfunction of the blood-cerebrospinal fluid (CSF) barrier, patients with
      noninflammatory occlusive hydrocephalus who had undergone external
      ventriculostomy were studied (n = 9; age range, 48 to 75 years). After
      administration of the first dose of piperacillin (6 g)-tazobactam (0.5 g) over 30
      min intravenously, serum and CSF were drawn repeatedly and analyzed by high
      performance liquid chromatography. Pharmacokinetics were determined by
      noncompartmental analysis. Maximum concentrations of piperacillin in CSF ranged
      from 8.67 to <0.37 mg/liter (median, 3.42 mg/liter), and those of tazobactam
      ranged from 1.37 to 0.11 mg/liter (median, 0.45 mg/liter). CSF maxima were
      observed, in median, 1.5 and 2 h after the end of the infusion. Elimination in
      CSF was considerably slower than in serum (median half-life at beta phase for
      piperacillin, 5.9 h in CSF versus 1.47 h in serum; for tazobactam, 6.1 h versus
      1.34 h). For tazobactam, the ratio of the area under the concentration-time curve
      (AUC) in CSF to the AUC in serum was approximately three times as high as that
      for piperacillin (medians, 0.106 versus 0.034). In view of the tazobactam
      concentrations in CSF observed in this study, the practice of using a constant
      concentration of 4 mg of tazobactam per liter for MIC determination is inadequate
      for intracranial infections. Larger amounts of tazobactam than the standard dose
      of 0.5 g three times daily may be necessary for CNS infections.

PMID- 9145858
TI  - Glycosylated flavones as selective inhibitors of topoisomerase IV.
AB  - Three flavonoids which promoted Escherichia coli topoisomerase IV-dependent DNA
      cleavage were isolated from cottonseed flour and identified as quercetin 3-O-beta
      D-glucose-[1,6]-O-alpha-L-rhamnose (rutin), quercetin 3-O-beta-D-galactose-[1,6]
      O-alpha-L-rhamnose, and quercetin 3-O-beta-D-glucose (isoquercitrin). The most
      active one (rutin) also inhibited topoisomerase IV-dependent decatenation
      activity (50% inhibitory concentration, 64 microg/ml) and induced the SOS
      response of a permeable E. coli strain. Derivatives of quercetin glycosylated at
      position C-3 were shown to induce two site-specific DNA cleavages of pBR322 DNA,
      which were mapped by DNA sequence analysis to the gene encoding resistance to
      tetracycline. Cleavage at these sites was hardly detectable in cleavage reactions
      with quercetin or fluoroquinolones. None of the three flavonoids isolated from
      cottonseeds had any stimulatory activity on E. coli DNA gyrase-dependent or calf
      thymus topoisomerase II-dependent DNA cleavage, and they were therefore specific
      to topoisomerase IV. These results show that selective inhibitors of
      topoisomerase IV can be derived from the flavone structure. This is the first
      report on a DNA topoisomerase inhibitor specific for topoisomerase IV.

PMID- 9145859
TI  - Galactose oxidase-glucan binding domain fusion proteins as targeting inhibitors
      of dental plaque bacteria.
AB  - In order to inhibit the growth of bacteria present in the human oral cavity, a
      novel system which targets antimicrobial agents to dental plaque has been
      developed. This system involves a hybrid protein consisting of a peptide
      expressing the bactericidal properties of galactose oxidase (GAO) fused to the
      glucan binding domain (GBD) of the Streptococcus mutans glucosyltransferase-S
      enzyme. A gene encoding GAO from the fungus Fusarium sp. has been inserted into
      an Escherichia coli expression vector and fused to sequences encoding the GBD,
      which binds to the glucans synthesized by oral streptococci. Bacterial extracts
      expressing the hybrid protein were tested for their ability to target the GAO
      activity to an in vitro plaque model consisting of streptococcal cells bound to
      microtiter plate wells. The binding of the hybrid protein to the streptococcal
      cells through its GBD and the dependence of binding on the production of glucans
      by bacteria were demonstrated. Furthermore, killing of three different species of
      oral streptococci by bound hybrid protein in conjunction with the galactose
      lactoperoxidase-iodide cytotoxic system has been demonstrated. These results
      suggest a novel strategy for controlling dental plaque formation as well as
      dental caries in humans.

PMID- 9145860
TI  - Microplate alamar blue assay versus BACTEC 460 system for high-throughput
      screening of compounds against Mycobacterium tuberculosis and Mycobacterium
      avium.
AB  - In response to the need for rapid, inexpensive, high-throughput assays for
      antimycobacterial drug screening, a microplate-based assay which uses Alamar blue
      reagent for determination of growth was evaluated. MICs of 30 antimicrobial
      agents against Mycobacterium tuberculosis H37Rv, M. tuberculosis H37Ra, and
      Mycobacterium avium were determined in the microplate Alamar blue assay (MABA)
      with both visual and fluorometric readings and compared to MICs determined in the
      BACTEC 460 system. For all three mycobacterial strains, there was < or = 1
      dilution difference between MABA and BACTEC median MICs in four replicate
      experiments for 25 to 27 of the 30 antimicrobics. Significant differences between
      MABA and BACTEC MICs were observed with 0, 2, and 5 of 30 antimicrobial agents
      against H37Rv, H37Ra, and M. avium, respectively. Overall, MICs determined either
      visually or fluorometrically in MABA were highly correlated with those determined
      in the BACTEC 460 system, and visual MABA and fluorometric MABA MICs were highly
      correlated. MICs of rifampin, rifabutin, minocycline, and clarithromycin were
      consistently lower for H37Ra compared to H37Rv in all assays but were similar for
      most other drugs. M. tuberculosis H37Ra may be a suitable surrogate for the more
      virulent H37Rv strain in primary screening of compounds for antituberculosis
      activity. MABA is sensitive, rapid, inexpensive, and nonradiometric and offers
      the potential for screening, with or without analytical instrumentation, large
      numbers of antimicrobial compounds against slow-growing mycobacteria.

PMID- 9145861
TI  - Antibacterial activity of BMS-180680, a new catechol-containing monobactam.
AB  - The in vitro activities of a new catechol-containing monobactam, BMS-180680 (SQ
      84,100), were compared to those of aztreonam, ceftazidime, imipenem, piperacillin
      tazobactam, ciprofloxacin, amikacin, and trimethoprim-sulfamethoxazole. BMS
      180680 was often the most active compound against many species of the family
      Enterobacteriaceae, with MICs at which 90% of the isolates were inhibited
      (MIC90s) of < or = 0.5 microg/ml for Escherichia coli, Klebsiella spp.,
      Citrobacter diversus, Enterobacter aerogenes, Serratia marcescens, Proteus spp.,
      and Providencia spp. BMS-180680 had moderate activities (MIC90s of 2 to 8
      microg/ml) against Citrobacter freundii, Morganella morganii, Shigella spp., and
      non-E. aerogenes Enterobacter spp. BMS-180680 was the only antibiotic evaluated
      that was active against >90% of the Pseudomonas aeruginosa (MIC90, 0.25
      microg/ml), Burkholderia cepacia, and Stenotrophomonas maltophilia (MIC90s, 1
      microg/ml) strains tested. BMS-180680 was inactive against most strains of
      Pseudomonas fluorescens, Pseudomonas stutzeri, Pseudomonas diminuta, and
      Burkholderia pickettii. BMS-180680 was moderately active (MIC90s of 4 to 8
      microg/ml) against Alcaligenes spp. and Acinetobacter lwoffii and less active
      (MIC90, 16 microg/ml) against Acinetobacter calcoaceticus-Acinetobacter baumanii
      complex. BMS-180680 lacked activity against gram-positive bacteria and anaerobic
      bacteria. Both tonB and cir fiu double mutants of E. coli had greatly decreased
      susceptibility to BMS-180680. Of the TEM, PSE, and chromosomal-encoded beta
      lactamases tested, only the K1 enzyme hydrolyzed BMS-180680 to any measurable
      extent. Like aztreonam, BMS-180680 bound preferentially to penicillin-binding
      protein 3. The MICs of BMS-180680 were not influenced by the presence of hematin
      or 5% sheep blood in the test medium or with incubation in an atmosphere
      containing 5% CO2. BMS-180680 MICs obtained under strict anaerobic conditions
      were significantly higher than those obtained in ambient air.

PMID- 9145863
TI  - Mapping the regions carrying the three contiguous antibiotic resistance genes
      aadE, sat4, and aphA-3 in the genomes of staphylococci.
AB  - Tn5405 (12 kb) is a staphylococcal composite transposon delimited by two inverted
      copies of IS1182, one of which contains IS1181. The internal part of this
      transposon carries three antibiotic resistance genes, aphA-3, aadE, and sat4, and
      three open reading frames (ORFs), orfx, orfy, and orfz, of unknown function. The
      dispersion of Tn5405 and the genes and ORFs included in this transposon were
      investigated in 50 epidemiologically unrelated staphylococci carrying aphA-3.
      Twenty-three maps, distinguishable by the presence or absence of the investigated
      genes or ORFs and/or by the sizes of the restriction fragments carrying them,
      were identified. Four isolates carried Tn5405, and 15 other isolates contained a
      Tn5405-related element. IS1182 was not detected in the aphA-3 regions mapped in
      31 isolates which carried the following combinations: orfx, orfy, aadE, sat4, and
      aphA-3 +/- orfz; orfy, aadE, sat4, and aphA-3 +/- orfz; and aadE, sat4, aphA-3,
      and orfz. In all isolates, the genes and ORFs investigated were in relative
      positions similar to those in Tn5405. Thus, the internal part of Tn5405 appeared
      to be partially conserved with the maintenance, in all of the isolates, of at
      least the three antibiotic resistance genes.

PMID- 9145862
TI  - Removal of human immunodeficiency virus type 1 (HIV-1) protease inhibitors from
      preparations of immature HIV-1 virions does not result in an increase in
      infectivity or the appearance of mature morphology.
AB  - The processing of gag and gag-pol polyproteins by human immunodeficiency virus
      type 1 (HIV-1) protease is a crucial step in the formation of infectious HIV-1
      virions. In this study, we examine whether particles produced in the presence of
      inhibitors of HIV-1 protease can subsequently undergo gag polyprotein cleavage
      with restoration of infectivity following removal of the inhibitors. Viral
      particles produced during 7 days of culture in the presence of the protease
      inhibitors KNI-272 (10 microM) and saquinavir (5 microM) contained predominantly
      p55gag polyprotein but little or no p24gag cleavage product. Following
      resuspension of the particles in medium free of the inhibitor, some gag
      polyprotein processing was detected in particles produced from the KNI-272
      treated cells, but not from the saquinavir-treated cells within the first 3 h.
      However, the majority of the protein remained as p55gag throughout a 48-h
      experimental period. The infectivity (50% tissue culture infective dose per
      milliliter) of the viral particles from KNI-272-treated cells was 10(6)-fold
      lower than that of control particles and did not significantly increase over the
      48 h after the inhibitor was removed, despite the apparent return of protease
      function in a subset of these virions. This failure to restore infectivity was
      due neither to a reduction in the number of particles produced by protease
      inhibitor-treated cells nor to a failure of HIV RNA to be packaged in the
      virions. These particles also failed to express the mature phenotype by electron
      microscopy. Thus, while some processing of the gag polyprotein can occur in
      isolated HIV virions, this does not appear to be sufficient to restore
      infectivity in the majority of particles. This finding suggests that there may be
      constraints on postbudding polyprotein processing in the production of viable
      particles. These results should have positive implications regarding the use of
      protease inhibitors as anti-HIV drugs.

PMID- 9145864
TI  - Susceptibilities of 228 penicillin- and erythromycin-susceptible and -resistant
      pneumococci to RU 64004, a new ketolide, compared with susceptibilities to 16
      other agents.
AB  - The susceptibilities of 228 penicillin- and erythromycin-susceptible and 
      resistant pneumococci to RU 64004, a new ketolide, were tested by agar dilution,
      and the results were compared with those for penicillin G, erythromycin,
      azithromycin, clarithromycin, rokitamycin, clindamycin, pristinamycin,
      ciprofloxacin, sparfloxacin, trimethoprim-sulfamethoxazole, doxycycline,
      chloramphenicol, cefuroxime, ceftriaxone, imipenem, and vancomycin. RU 64004 was
      very active against all strains tested, with MICs at which 90% of the isolates
      are inhibited (MIC90s) of 0.016 microg/ml for erythromycin-susceptible strains
      (MIC, < or = 0.25 microg/ml) and 0.25 microg/ml for erythromycin-resistant
      strains (MIC, > or = 0.5 microg/ml). All other macrolides had MIC90s of 0.03 to
      0.25 and > or = 128 microg/ml for erythromycin-susceptible and -resistant
      strains, respectively. Among erythromycin-resistant strains, clindamycin MICs for
      28 of 91 (30.7%) were < or = 0.125 microg/ml. Pristinamycin MICs for all strains
      were < or = 1.0 microg/ml. MIC90s of ciprofloxacin and sparfloxacin were 4.0 and
      0.25 microg/ml, respectively, and were unaffected by susceptibility to penicillin
      or erythromycin. Vancomycin and imipenem inhibited all strains at < or = 0.5 and
      < or = 0.25 microg/ml, respectively. MICs of cefuroxime and cefotaxime rose with
      those of penicillin G. MICs of trimethoprim-sulfamethoxazole, doxycycline, and
      chloramphenicol were variable but were generally higher for penicillin- and
      erythromycin-resistant strains. RU 64004 is the first member of the macrolide
      group which has low MICs for erythromycin-resistant pneumococci.

PMID- 9145865
TI  - Antianaerobic activity of the ketolide RU 64004 compared to activities of four
      macrolides, five beta-lactams, clindamycin, and metronidazole.
AB  - Agar dilution methodology (with added Oxyrase in the case of the macrolide group
      to allow incubation without added CO2) was used to compare the activity of RU
      64004, a new ketolide, with the activities of erythromycin, azithromycin,
      clarithromycin, roxithromycin, clindamycin, amoxicillin with and without
      clavulanate, piperacillin with and without tazobactam, metronidazole, and
      imipenem against 379 anaerobes. Overall, RU 64004 yielded an MIC at which 50% of
      the isolates are inhibited (MIC50) of 1.0 microg/ml and an MIC90 of 16.0
      microg/ml. In comparison, MIC50s and MIC90s of erythromycin, azithromycin,
      clarithromycin, and roxithromycin were 2.0 to 8.0 and >64.0 microg/ml,
      respectively. MICs of macrolides, including RU 64004, were higher for Bacteroides
      ovatus, Fusobacterium varium, Fusobacterium mortiferum, and Clostridium difficile
      than for the other species. RU 64004 was more active against gram-positive rods
      and cocci, Prevotella and Porphyromonas spp., and fusobacteria other than F.
      mortiferum and F. varium than against the Bacteroides fragilis group. Overall
      MIC50s and MIC90s (in micrograms per milliliter), respectively, of other
      compounds were as follows: clindamycin, 1.0 and 16.0; amoxicillin, 4.0 and 64.0;
      amoxicillin-clavulanate, 0.5 and 4.0; piperacillin, 8.0 and >64.0; piperacillin
      tazobactam, 1.0 and 16.0; metronidazole, 1.0 and 4.0; and imipenem, 0.25 and 1.0.

PMID- 9145866
TI  - Efficacy of trimethoprim in murine experimental infection with a thymidine kinase
      deficient mutant of Escherichia coli.
AB  - The antimicrobial activity of trimethoprim is antagonized by thymidine in in
      vitro susceptibility tests. The purpose of this investigation was to determine
      whether this antagonism also occurred during experimental infection in mice,
      which have high serum thymidine concentrations. We derived a mutant strain of
      Escherichia coli, TT-48, incapable of utilizing exogenous thymidine from parent
      strain E. coli KC-14 and then investigated the in vitro and in vivo antimicrobial
      activities of trimethoprim, sulfamethoxazole, cefdinir, and ofloxacin against
      these strains. E. coli TT-48 lacked the activity of thymidine kinase, which
      catalyzes the conversion of thymidine to thymidylate, but its growth curve
      remained close to that of the parent strain. The MICs of all of the antimicrobial
      agents tested, except cefdinir, for the mutant strain were slightly inferior to
      those for the parent strain. The bactericidal effect of trimethoprim against the
      parent strain was antagonized by thymidine at concentrations of more than 1
      microg/ml, while that against the mutant strain was not affected by thymidine
      even at the highest concentration (10 microg/ml). The therapeutic efficacy of
      trimethoprim in experimental murine infections was significantly higher when the
      mutant rather than the parent strain was used, whereas the therapeutic efficacy
      of cefdinir or ofloxacin, whose antimicrobial action is independent of folic acid
      synthesis, was the same with both strains. Unexpectedly, sulfamethoxazole also
      had similar efficacy against both strains. Thus, high thymidine concentrations
      antagonized the antimicrobial activity of trimethoprim in vitro and in vivo.

PMID- 9145867
TI  - Antibacterial effect of the adhering human Lactobacillus acidophilus strain LB.
AB  - The spent culture supernatant of the human Lactobacillus acidophilus strain LB
      produces an antibacterial activity against a wide range of gram-negative and gram
      positive pathogens. It decreased the in vitro viability of Staphylococcus aureus,
      Listeria monocytogenes, Salmonella typhimurium, Shigella flexneri, Escherichia
      coli, Klebsiella pneumoniae, Bacillus cereus, Pseudomonas aeruginosa, and
      Enterobacter spp. In contrast, it did not inhibit lactobacilli and
      bifidobacteria. The activity was heat stable and relatively sensitive to
      enzymatic treatments and developed under acidic conditions. The antimicrobial
      activity was independent of lactic acid production. Activity against S.
      typhimurium SL1344 infecting human cultured intestinal Caco-2 cells was observed
      as it was in the conventional C3H/He/oujco mouse model with S. typhimurium C5
      infection and oral treatment with the LB spent culture supernatant.

PMID- 9145868
TI  - Efficacies of piperacillin-tazobactam and cefepime in rats with experimental
      intra-abdominal abscesses due to an extended-spectrum beta-lactamase-producing
      strain of Klebsiella pneumoniae.
AB  - The in vivo activities of piperacillin-tazobactam and cefepime were compared with
      those of ticarcillin-clavulanate, ceftazidime, cefotaxime, and imipenem in a rat
      model of intra-abdominal abscess with a strain of Klebsiella pneumoniae
      elaborating an extended-spectrum beta-lactamase (TEM-26). With the exception of
      ceftazidime, all of the antimicrobial agents significantly reduced bacterial
      counts within abscesses at the end of therapy compared with those in untreated
      controls. Residual viable cell counts (mean +/- standard deviation in log10
      CFU/gram) were as follows: control, 8.76 +/- 0.97; ceftazidime, 8.00 +/- 0.76;
      piperacillin-tazobactam, 3.87 +/- 1.72; ticarcillin-clavulanate, 3.74 +/- 1.34;
      cefepime, 3.15 +/- 1.19; cefotaxime, 2.61 +/- 0.77; imipenem, 2.41 +/- 0.93.
      Imipenem was more effective than either of the inhibitor combinations (P < 0.05).
      Cefotaxime was unexpectedly effective given its poor in vivo activity against
      this organism in our earlier studies, which used a different dose and total
      duration of therapy (L. B. Rice, J. D. C. Yao, K. Klimm, G. M. Eliopoulos, and R.
      C. Moellering, Jr., Antimicrob. Agents Chemother. 35:1243-1244, 1991). These
      observations suggest that the effectiveness of cephalosporins in the treatment of
      experimental infections caused by extended-spectrum beta-lactamase-producing K.
      pneumoniae may be highly dependent on dosing regimens, even for a specific
      organism and site of infection.

PMID- 9145870
TI  - Pentostam induces resistance to antimony and the preservative chlorocresol in
      Leishmania donovani promastigotes and axenically grown amastigotes.
AB  - An axenic amastigote culture system was utilized to directly assess the stage
      specific antileishmanial effects of antimony on amastigotes of Leishmania
      donovani devoid of the macrophage host cell. Pentostam, which contains antimony
      in the form of sodium stibogluconate and the preservative chlorocresol, was used.
      Cell density was quantified by measuring the activity of the stable enzyme
      ornithine decarboxylase. Dose-response curve analyses show that Leishmania
      promastigotes are susceptible to Pentostam, with the 50% inhibitory concentration
      (IC50) being 104 microg/ml, while amastigotes are more susceptible, with the IC50
      being 24 microg/ml. Promastigotes and amastigotes are also susceptible to
      chlorocresol, with IC50s being 1.27 and 1.82 microg/ml, respectively. Given that
      promastigotes are insensitive to antimony, these results suggest that the
      increased susceptibility of amastigotes to Pentostam is due to the stage-specific
      activity of sodium stibogluconate. To further study this phenomenon, spontaneous
      resistance to Pentostam was induced in L. donovani promastigotes by increasing
      the concentration of Pentostam in the growth medium in a stepwise fashion. Two
      mutants, Ld1S.04 and Ld1S.20, grew at 0.4 and 2.0 mg of Pentostam per ml,
      respectively. Promastigotes of these mutants were 11 and 21 times, respectively,
      more resistant to Pentostam than the wild type. Amastigotes were 40 and 148
      times, respectively, more resistant than the wild type. The mutants were also
      chlorocresol resistant; promastigotes were 6 and 9 times, respectively, more
      resistant than the wild type, and amastigotes were 14 and 35 times, respectively,
      more resistant than the wild type. These data show that resistance to Pentostam
      induced in antimony-insensitive promastigotes is manifested in amastigotes as
      resistance both to pentavalent antimony and to chlorocresol. The axenic
      amastigote system is a unique tool which enables direct evaluation of the
      activity of antileishmanial compounds on the amastigote devoid of its host cell.

PMID- 9145869
TI  - Antiviral activity of the dihydropyrone PNU-140690, a new nonpeptidic human
      immunodeficiency virus protease inhibitor.
AB  - PNU-140690 is a member of a new class of nonpeptidic human immunodeficiency virus
      (HIV) protease inhibitors (sulfonamide-containing 5,6-dihydro-4-hydroxy-2
      pyrones) discovered by structure-based design. PNU-140690 has excellent potency
      against a variety of HIV type 1 (HIV-1) laboratory strains and clinical isolates,
      including those resistant to the reverse transcriptase inhibitors zidovudine or
      delavirdine. When combined with either zidovudine or delavirdine, PNU-140690
      contributes to synergistic antiviral activity. PNU-140690 is also highly active
      against HIV-1 variants resistant to peptidomimetic protease inhibitors,
      underscoring the structural distinctions between PNU-140690 and substrate analog
      protease inhibitors. PNU-140690 retains good antiviral activity in vitro in the
      presence of human plasma proteins, and preclinical pharmacokinetic studies
      revealed good oral bioavailability. Accordingly, PNU-140690 is a candidate for
      clinical evaluation.

PMID- 9145871
TI  - Effect of food intake on pharmacokinetics of oral artemisinin in healthy
      Vietnamese subjects.
AB  - The influence of food intake on the pharmacokinetics of artemisinin was studied
      with six healthy Vietnamese male subjects. In a crossover study, artemisinin
      capsules (500 mg) were administered with and without food after an overnight
      fast. Plasma samples were obtained up to 24 h after intake of each drug.
      Measurement of artemisinin concentrations was performed by high-performance
      liquid chromatography with electrochemical detection. Tolerance was evaluated
      according to subjective and objective findings, including repeated physical
      examinations, routine blood investigations, and electrocardiograms.
      Pharmacokinetics were analyzed with a noncompartmental method and with a one
      compartment model. This model had either zero-order or first-order input. No
      statistically significant differences were found between the results of the two
      experimental conditions. Specifically, there were no consistent differences in
      parameters most likely to be affected by food intake, including absorption
      profile, absorption rate, bioavailability (f) (as reflected in area under the
      concentration time curve [AUC]), and drug clearance. Some mean +/- standard
      deviation parameters after food were as follows: maximum concentration of drug in
      serum (Cmax), 443 +/- 224 microg x liter(-1); time to Cmax, 1.78 +/- 1.2 h; AUC,
      2,092 +/- 1,441 ng x ml(-1) x h, apparent clearance/f, 321 +/- 167 liter x h(-1);
      mean residence time, 4.42 +/- 1.31 h; and time at which half of the terminal
      value was reached, 0.97 +/- 0.68 h. The total amount of artemisinin excreted in
      urine was less than 1% of the dose. We conclude that food intake has no major
      effect on artemisinin pharmacokinetics. In addition, we conclude tentatively that
      artemisinin is cleared by the liver, that this clearance does not depend on liver
      blood flow (i.e., that artemisinin is a so-called low-clearance drug), and that
      absorption of the drug is not affected by food intake.

PMID- 9145872
TI  - Activities of levofloxacin, ofloxacin, and ciprofloxacin, alone and in
      combination with amikacin, against acinetobacters as determined by checkerboard
      and time-kill studies.
AB  - A total of 101 Acinetobacter genospecies (77 Acinetobacter baumannii strains and
      24 non-A. baumannii strains) were tested for their susceptibilities to
      levofloxacin, ofloxacin, and ciprofloxacin and for synergy between the quinolones
      and amikacin by checkerboard titration and time-kill analyses. The MICs at which
      50% of the isolates are inhibited (MIC50)/MIC90s for the 101 strains were as
      follows (in micrograms per milliliter): levofloxacin, 0.25/16.0; ofloxacin,
      0.5/32.0; ciprofloxacin, 0.25/> 64.0; and amikacin, 1.0/> 32.0. At empiric
      breakpoints of < or = 2.0 microg/ml, 61% of the strains were susceptible to all
      three quinolones. At a breakpoint of < or = 16.0 microg/ml, 84% of the strains
      were susceptible to amikacin. Checkerboard titrations yielded synergistic
      fractional inhibitory concentration (FIC) indices (< or = 0.5) for one strain
      with levofloxacin and amikacin and for two strains with ofloxacin and amikacin.
      Indices of > 0.5 to 1.0 were seen for 57, 54, and 55 strains with levofloxacin
      plus amikacin, ofloxacin plus amikacin, and ciprofloxacin plus amikacin,
      respectively, and indices of > 1.0 in 43, 45, and 46 strains, respectively, were
      found with the above three combinations. No strains yielded antagonistic FIC
      indices (> 4.0). Most FIC results of > 1.0 occurred in strains for which the
      quinolone MICs were > 2.0 microg/ml and for which the amikacin MICs were > or =
      32.0 microg/ml. By contrast, synergy (defined as > or = 2 log10 decrease compared
      to the more active compound alone by time-kill analysis) was found in all seven
      strains tested for which the quinolone MICs were < or = 2.0 microg/ml. For eight
      other strains for which the quinolone MICs were > 2.0 microg/ml as determined by
      time-kill analysis, quinolone and amikacin concentrations in combination were
      usually too high to permit clinical use. Time-kill analysis was found to be more
      sensitive in detecting synergy than was the checkerboard method.

PMID- 9145873
TI  - Penetration of dapsone into pulmonary lining fluid of human immunodeficiency
      virus type 1-infected patients.
AB  - We studied the penetration of dapsone into the epithelial lining fluid (ELF) of
      sixteen human immunodeficiency virus type 1-infected patients who had received
      the drug at a dose of 100 mg twice weekly as primary prophylaxis for Pneumocystis
      carinii pneumonia. Bronchoscopy, bronchoalveolar lavage (BAL), and venipuncture
      were performed for each patient at a specific time after administration of the
      last dose of dapsone. Dapsone concentrations in plasma and BAL were determined by
      high-performance liquid chromatography. The apparent volume of ELF recovered by
      BAL was determined by using urea as an endogenous marker. The mean concentrations
      of dapsone in ELF at 2 h (five patients), 4 h (three patients), 12 h (two
      patients), 24 h (three patients), and 48 h (three patients) were 0.95, 0.70,
      1.55, 0.23, and 0.45 mg/liter, respectively, while concentrations in plasma were
      1.23, 0.79, 1.31, 0.83, and 0.18 mg/liter, respectively. Dapsone concentrations
      in ELF were 76, 79, 115, 65, and 291% of those observed in plasma at the same
      times, respectively. These data show that dapsone is well distributed into ELF
      and that a twice-weekly 100-mg prophylactic regimen results in sustained
      concentrations in this compartment.

PMID- 9145874
TI  - 1592U89, a novel carbocyclic nucleoside analog with potent, selective anti-human
      immunodeficiency virus activity.
AB  - 1592U89, (-)-(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclo
      pentene-1-methanol, is a carbocyclic nucleoside with a unique biological profile
      giving potent, selective anti-human immunodeficiency virus (HIV) activity.
      1592U89 was selected after evaluation of a wide variety of analogs containing a
      cyclopentene substitution for the 2'-deoxyriboside of natural deoxynucleosides,
      optimizing in vitro anti-HIV potency, oral bioavailability, and central nervous
      system (CNS) penetration. 1592U89 was equivalent in potency to 3'-azido-3'
      deoxythymidine (AZT) in human peripheral blood lymphocyte (PBL) cultures against
      clinical isolates of HIV type 1 (HIV-1) from antiretroviral drug-naive patients
      (average 50% inhibitory concentration [IC50], 0.26 microM for 1592U89 and 0.23
      microM for AZT). 1592U89 showed minimal cross-resistance (approximately twofold)
      with AZT and other approved HIV reverse transcriptase (RT) inhibitors. 1592U89
      was synergistic in combination with AZT, the nonnucleoside RT inhibitor
      nevirapine, and the protease inhibitor 141W94 in MT4 cells against HIV-1 (IIIB).
      1592U89 was anabolized intracellularly to its 5'-monophosphate in CD4+ CEM cells
      and in PBLs, but the di- and triphosphates of 1592U89 were not detected. The only
      triphosphate found in cells incubated with 1592U89 was that of the guanine analog
      (-)-carbovir (CBV). However, the in vivo pharmacokinetic, distribution, and
      toxicological profiles of 1592U89 were distinct from and improved over those of
      CBV, probably because CBV itself was not appreciably formed from 1592U89 in cells
      or animals (<2%). The 5'-triphosphate of CBV was a potent, selective inhibitor of
      HIV-1 RT, with Ki values for DNA polymerases (alpha, beta, gamma, and epsilon
      which were 90-, 2,900-, 1,200-, and 1,900-fold greater, respectively, than for RT
      (Ki, 21 nM). 1592U89 was relatively nontoxic to human bone marrow progenitors
      erythroid burst-forming unit and granulocyte-macrophage CFU (IC50s, 110 microM)
      and human leukemic and liver tumor cell lines. 1592U89 had excellent oral
      bioavailability (105% in the rat) and penetrated the CNS (rat brain and monkey
      cerebrospinal fluid) as well as AZT. Having demonstrated an excellent preclinical
      profile, 1592U89 has progressed to clinical evaluation in HIV-infected patients.

PMID- 9145875
TI  - Combination of mutations in human immunodeficiency virus type 1 reverse
      transcriptase required for resistance to the carbocyclic nucleoside 1592U89.
AB  - The carbocyclic nucleoside 1592U89 is a selective inhibitor of the human
      immunodeficiency virus (HIV), targeting the reverse transcriptase (RT). In vitro
      selection studies were undertaken to generate resistant variants with both HIV
      type 1 (HIV-1) wild-type strain HIV-1(HXB2) and 3'-azido-3'-deoxythymidine (AZT)
      resistant strain HIV-1(RTMC). At least two or three mutations in RT were required
      to produce a 10-fold reduction in susceptibility. The first RT mutation selected
      was at codon 184, methionine (M) to valine (V), for HIV-1(HXB2) and HIV-1(RTMC),
      conferring two- and fivefold resistance, respectively. Two additional mutations
      were selected with HIV-1(HXB2), either leucine (L) 74 to V and lysine (K) 65 to
      arginine (R) (first-passage series) or L74 to V and tyrosine (Y) 115 to
      phenylalanine (F) (second-passage series). Cloned variants, obtained from the
      1592U89 selection, were either double RT mutants 65R/184V and 74V/184V or triple
      RT mutant 74V/115Y/184V. Molecular clones were constructed with single, double,
      and triple combinations of these mutations for resistance analysis with different
      RT inhibitors. Each individual mutation conferred only low-level resistance (two-
      to fourfold) to 1592U89 in the HXB2 background. Double mutants containing the
      184V mutation and triple mutants showed slightly greater levels of resistance to
      1592U89 (7- to 11-fold). Some of the 1592U89-resistant variants were cross
      resistant with 2',3'-dideoxycytidine, 2',3'-dideoxyinosine, and (-)-2'-deoxy-3'
      thiacytidine, but none were resistant to 2',3'-didehydro-3'-deoxythymidine or
      AZT.

PMID- 9145876
TI  - Unique intracellular activation of the potent anti-human immunodeficiency virus
      agent 1592U89.
AB  - The anabolism of 1592U89, (-)-(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9
      yl]-2-cyclo pentene-1-methanol, a selective inhibitor of human immunodeficiency
      virus (HIV), was characterized in human T-lymphoblastoid CD4+ CEM cells. 1592U89
      was ultimately anabolized to the triphosphate (TP) of the guanine analog (-)
      carbovir (CBV), a potent inhibitor of HIV reverse transcriptase. However, less
      than 2% of intracellular 1592U89 was converted to CBV, an amount insufficient to
      account for the CBV-TP levels observed. 1592U89 was anabolized to its 5'
      monophosphate (MP) by the recently characterized enzyme adenosine
      phosphotransferase, but neither its diphosphate (DP) nor its TP was detected. The
      MP, DP, and TP of CBV were found in cells incubated with either 1592U89 or CBV,
      with CBV-TP being the major phosphorylated species. We confirmed that CBV is
      phosphorylated by 5'-nucleotidase and that mycophenolic acid increased the
      formation of CBV-TP from CBV 75-fold. However, mycophenolic acid did not
      stimulate 1592U89 anabolism to CBV-TP. The adenosine deaminase inhibitor erythro
      9-(2-hydroxy-3-nonyl)adenine (EHNA) did not inhibit CBV-TP formation from CBV or
      1592U89, whereas the adenylate deaminase inhibitor 2'-deoxycoformycin selectively
      inhibited 1592U89 anabolism to CBV-TP and reversed the antiviral activity of
      1592U89. 1592U89-MP was not a substrate for adenylate deaminase but was a
      substrate for a distinct cytosolic deaminase that was inhibited by 2'
      deoxycoformycin-5'-MP. Thus, 1592U89 is phosphorylated by adenosine
      phosphotransferase to 1592U89-MP, which is converted by a novel cytosolic enzyme
      to CBV-MP. CBV-MP is then further phosphorylated to CBV-TP by cellular kinases.
      This unique activation pathway enables 1592U89 to overcome the pharmacokinetic
      and toxicological deficiencies of CBV while maintaining potent and selective anti
      HIV activity.

PMID- 9145878
TI  - Pharmacokinetics of gentamicin at traditional versus high doses: implications for
      once-daily aminoglycoside dosing.
AB  - Two doses of gentamicin (2 and 7 mg/kg of body weight) were administered to 11
      healthy volunteers in a randomized, crossover single-dose study to compare their
      pharmacokinetics. Doses were infused over 1 h with a syringe infusion pump, and
      14 concentrations in sera were obtained over an 8-h period. Concentration in
      serum versus time data were fitted to a two-compartment pharmacokinetic model. In
      addition, to mimic the clinical setting, subjects' data were fitted by the
      Sawchuk-Zaske method. Distributional and postdistributional peak concentrations,
      along with the last obtained concentration in serum, were utilized to compare the
      following pharmacokinetic variables: volume of distribution at steady state
      (Vss), half-life, clearance (CL), and maximum concentration in serum (Cmax). With
      two-compartment pharmacokinetic fitting, significant differences in distribution
      half-life (average, 21.8 and 41.6 min [P < or = 0.05]) and gentamicin CL (76.6 +/
      6.6 and 67.2 +/- 4.2 ml/min/1.73 m2 [P < or = 0.001]) were found between
      traditional-dose and high-dose groups, respectively. When the data for
      concentrations in sera were fitted to a one-compartment pharmacokinetic model by
      using either the distributional or the postdistributional Cmax, statistically
      significant differences (P < or = 0.001) were found between Vss, half-life, CL,
      and Cmax values for both dosage groups. The results show that the
      pharmacokinetics of gentamicin at a large dose differ significantly from those at
      the traditional dose. This information has direct implications for once-daily
      aminoglycoside (ODA) literature when the Cmax values reported are distributional
      and therefore show falsely high Cmax/MIC ratio estimates. In addition, ODA
      nomogram dosing tools developed with distributional Cmax values are probably
      inaccurate.

PMID- 9145877
TI  - Pharmacodynamic modeling of the in vivo interaction between cefotaxime and
      ofloxacin by using serum ultrafiltrate inhibitory titers.
AB  - The pharmacokinetics (PK) and pharmacodynamics (PD) of cefotaxime and ofloxacin
      and of their combination were examined in a three-period randomized crossover
      study involving 12 healthy adults. The PK of cefotaxime and ofloxacin were
      modeled. PD was assessed from the predicted concentrations in serum and serum
      untrafiltrate inhibitory titers for 10 test organisms. An inhibitory sigmoid Emax
      model based on the probability of bacterial growth was used, where Emax = 1 and
      EC50 is the concentration resulting in a 50% probability of growth. The total
      body clearance (CL(T)) and volume of distribution at steady state (V(SS)) for
      cefotaxime were 0.236 liters/kg/h and 0.207 liters/kg, respectively, for the
      monotherapy and 0.231 liters/kg/h and 0.208 liters/kg for the combination
      therapy. Ofloxacin exhibited PK parameters of 0.143 liters/kg/h for CL(T) and
      1.20 liters/kg for V(SS) following the monotherapy and of 0.141 liters/kg/h for
      CL(T) and 1.16 liters/kg for V(SS) following combination therapy. For the
      combination therapy, an interaction term, theta, defined the type and relative
      extent of interaction. The range of observed theta values (-0.033 to 0.067) is
      consistent with an additive PD interaction according to standards similar to
      those used for the in vitro fractional inhibitory concentration index.

PMID- 9145879
TI  - Combination therapy with fluconazole and flucytosine in the murine model of
      cryptococcal meningitis.
AB  - This study elucidates the role of combined fluconazole and flucytosine as therapy
      for cryptococcosis in the murine model of meningitis. Three strains of
      Cryptococcus neoformans for which the range of fluconazole MICs was wide--2
      microg/ml (susceptible strain), 8 microg/ml (moderately susceptible strain), and
      32 microg/ml (resistant strain)--were used for infection. One day postinfection,
      the mice were randomized into eight treatment groups: placebo; flucytosine (40
      mg/kg of body weight/day); fluconazole at 3 mg/kg/day (low dosage), 10 mg/kg/day
      (moderate dosage), or 20 mg/kg/day (high dosage); and combined flucytosine and
      fluconazole at low, moderate, or high doses of fluconazole. Three major findings
      were demonstrated: (i) correlation between the MICs for the isolates and the in
      vivo effectiveness of fluconazole as assessed by the reduction in cryptococcal
      brain burden, (ii) a dose-response curve (a higher dose of fluconazole was
      significantly more efficacious than a lower dose [P < 0.001]), and (iii)
      synergism between fluconazole and flucytosine (therapy with a combination of
      fluconazole and flucytosine was superior to therapy with either agent alone [P <
      0.01]).

PMID- 9145880
TI  - In vitro activity of SCH-56592 and comparison with activities of amphotericin B
      and itraconazole against Aspergillus spp.
AB  - In this study, we investigated the in vitro activity of SCH-56592 (SCH), a new
      triazole antifungal agent. We compared the activity of SCH with those of
      itraconazole (ITZ) and amphotericin B (AB) against 60 clinical isolates of
      Aspergillus spp. by using a microtiter format. Incubation was done at 37 degrees
      C for 48 h, and MIC endpoints (no growth) were read visually. The medium used for
      all of the drugs was RPMI 1640 buffered with morpholinepropanesulfonic acid
      (MOPS) and supplemented with 2% glucose. MICs and minimum fungicidal
      concentrations (MFCs; killing of > or = 99.99%) were measured for all isolates.
      The geometric mean (GM) MICs and ranges (in micrograms per milliliter) were as
      follows: SCH, 0.09 and < or = 0.01 to 1; ITZ, 0.25 and 0.06 to 32; AB, 1.46 and
      0.25 to 32. Aspergillus terreus (n = 7) was markedly more susceptible to SCH (GM,
      0.05 microg/ml) and ITZ (GM, 0.07 microg/ml) than to AB (GM, 8.8 microg/ml). For
      all isolates, the GM MFCs and ranges (in micrograms per milliliter) were as
      follows: SCH, 3.64 and 0.125 to 16; ITZ, 15.09 and 0.125 to 32; AB, 10.3 and 1 to
      32. In the drug concentration range tested, 71, 32, and 64% of the isolates
      against which SCH, ITZ, and AB, respectively, were tested were killed. A
      reproducibility study was performed with 20% of the isolates; for 11 of the 12
      isolates retested, the MIC was the same or within 1 well of the original MIC of
      each drug. Therefore, in vitro mould testing of SCH is feasible and reproducible.
      SCH was found to be very active against all species of Aspergillus and at lower
      concentrations than either ITZ or AB.

PMID- 9145882
TI  - Emergence of the trimethoprim resistance gene dfrD in Listeria monocytogenes
      BM4293.
AB  - The sequence of the trimethoprim resistance gene of the 3.7-kb plasmid (pIP823)
      that confers high-level resistance (MIC, 1,024 microg/ml) to Listeria
      monocytogenes BM4293 was determined. The gene was identical to dfrD recently
      detected in Staphylococcus haemolyticus MUR313. The corresponding protein,
      S2DHFR, represents the second class of high-level trimethoprim-resistant
      dihydrofolate reductase identified in gram-positive bacteria. We propose that
      trimethoprim resistance in L. monocytogenes BM4293 could originate in
      staphylococci.

PMID- 9145881
TI  - Monotherapy versus beta-lactam-aminoglycoside combination treatment for gram
      negative bacteremia: a prospective, observational study.
AB  - The aim of the present study was to test whether the combination of a beta-lactam
      drug plus an aminoglycoside has advantage over monotherapy for severe gram
      negative infections. Of 2,124 patients with gram-negative bacteremia surveyed
      prospectively, 670 were given inappropriate empirical antibiotic treatment and
      the mortality rate in this group was 34%, whereas the mortality rate was 18% for
      1,454 patients given appropriate empirical antibiotic treatment (P = 0.0001). The
      mortality rates for patients given appropriate empirical antibiotic treatment
      were 17% for 789 patients given a single beta-lactam drug, 19% for 327 patients
      given combination treatment, 24% for 249 patients given a single aminoglycoside,
      and 29% for 89 patients given other antibiotics (P = 0.0001). When patients were
      stratified according to risk factors for mortality other than antibiotic
      treatment, combination therapy showed no advantage over treatment with a single
      beta-lactam drug except for neutropenic patients (odds ratio [OR] for mortality,
      0.5; 95% confidence interval [95% CI], 0.2 to 1.3) and patients with Pseudomonas
      aeruginosa bacteremia (OR, 0.7; 95% CI, 0.3 to 1.8). On multivariable logistic
      regression analysis including all risk factors for mortality, combination therapy
      had no advantage over therapy with a single beta-lactam drug. The mortality rate
      for patients treated with a single appropriate aminoglycoside was higher than
      that for patients given a beta-lactam drug in all strata except for patients with
      urinary tract infections. When the results of blood cultures were known, 1,878
      patients were available for follow-up. Of these, 816 patients were given a single
      beta-lactam drug, 442 were given combination treatment, and 193 were given a
      single aminoglycoside. The mortality rates were 13, 15, and 23%, respectively (P
      = 0.0001). Both on stratified and on multivariable logistic regression analyses,
      combination treatment showed a benefit over treatment with a single beta-lactam
      drug only for neutropenic patients (OR, 0.2; 95% CI, 0.05 to 0.7). In summary,
      combination treatment showed no advantage over treatment with an appropriate beta
      lactam drug in nonneutropenic patients with gram-negative bacteremia.

PMID- 9145883
TI  - Interpretive criteria for testing susceptibility of staphylococci to mupirocin.
AB  - To determine appropriate mupirocin susceptibility testing interpretive criteria,
      177 staphylococci were tested by agar dilution, disk diffusion, and E test. E
      test was found to be a reliable method for determining susceptibility of
      staphylococci to mupirocin. The agar dilution and disk diffusion results were
      plotted on a scattergram, and error rates were calculated. No errors were found
      with susceptibility breakpoints of > or = 4 microg/ml (MIC) and > or = 14 mm
      (zone diameter).

PMID- 9145884
TI  - Multiple antibiotic resistance in Stenotrophomonas maltophilia.
AB  - A cryptic multidrug resistance (MDR) system in Stenotrophomonas maltophilia, the
      expression of which is selectable by tetracycline, is described. Tetracycline
      resistance was the consequence of active efflux of the antibiotic, and it was
      associated with resistance to quinolones and chloramphenicol, but not to
      aminoglycosides or beta-lactam antibiotics. MDR is linked to the expression of an
      outer membrane protein (OMP54) both in a model system and in multidrug-resistant
      clinical isolates.

PMID- 9145885
TI  - Pharmacokinetics of zidovudine after rectal administration in human
      immunodeficiency virus-infected patients.
AB  - We evaluated the pharmacokinetics of rectally administered zidovudine (ZDV) in 10
      human immunodeficiency virus-infected adults. After rectal administration of an
      aqueous ZDV solution (250 mg of ZDV), mean peak ZDV levels were 1.3 +/- 0.7
      micromol/liter (mean +/- standard deviation) versus 5.0 +/- 2.2 micromol/liter (P
      < 0.0001) after oral intake of a 250-mg ZDV capsule. The half-life at beta phase
      was 87.8 +/- 39.6 min for rectally administered ZDV versus 55.8 +/- 20.1 min (P =
      0.035) for orally administered ZDV. The mean area under the concentration-time
      curve from 0 min to infinity was 232 +/- 181 micromol/liter x min after rectal
      administration versus 362 +/- 110 micromol/liter x min after oral intake.
      Although the two routes were not bioequivalent, ZDV was absorbed considerably
      after rectal administration, with a pharmacokinetic profile resembling that of a
      sustained-release device.

PMID- 9145886
TI  - Comparative in vitro activities of trovafloxacin (CP-99,219) against 445 gram
      positive isolates from patients with endocarditis and those with other
      bloodstream infections.
AB  - The in vitro activity of trovafloxacin (CP-99,219), a new fluoroquinolone, was
      compared with the in vitro activities of other commonly used quinolones and other
      antimicrobial agents against 445 gram-positive microorganisms isolated between
      1986 and 1995 from patients with endocarditis and those with other bloodstream
      infections. The MICs at which 90% of the isolates are inhibited (MIC90) of
      trovafloxacin for methicillin-susceptible staphylococci, viridans group
      streptococci, and enterococci were 0.06, 0.25, and 0.5 mg/liter, respectively.
      The MIC90 of trovafloxacin for vancomycin-resistant enterococci as well as for
      methicillin-resistant Staphylococcus aureus and methicillin-susceptible and
      ciprofloxacin-resistant S. aureus, isolated from sources other than blood, was 1
      mg/liter. For the quinolones the rank order of activity was trovafloxacin >
      sparfloxacin > ciprofloxacin = ofloxacin > pefloxacin. Depending on the species
      tested, trovafloxacin was 4- to 64-fold more active than ciprofloxacin. Further
      experimental and in vivo studies are warranted to evaluate the efficacy of
      trovafloxacin in the treatment of bacterial endocarditis and other infections
      caused by gram-positive organisms.

PMID- 9145887
TI  - Teicoplanin in cardiac surgery: intraoperative pharmacokinetics and
      concentrations in cardiac and mediastinal tissues.
AB  - The concentrations of teicoplanin in the sera and mediastinal and heart tissues
      of 23 patients undergoing cardiac surgery were measured after two regimens of
      teicoplanin administration. Intraoperative pharmacokinetic parameters were also
      obtained. Patients were randomized into two groups. Those in group 1 were given
      teicoplanin at 6 mg x kg(-1) intravenously at the time of induction of
      anesthesia. Patients in group 2 were given teicoplanin at 12 mg x kg(-1) during
      the same period. The maximum concentration in serum (71 +/- 20 and 131 +/- 44 mg
      x l(-1)), the minimum concentration in serum (3.6 +/- 1.3 and 6.8 +/- 2.1 mg x l(
      1)), the area under the concentration-time curve (AUC) from 0 to 12 h (108 +/- 20
      and 217 +/- 38 microg x h x ml(-1)), and the AUC from 0 h to infinity (154 +/- 36
      and 292 +/- 77 microg x h x ml(-1)) were twice as high after 12-mg x kg(-1)
      injections as after 6-mg x kg(-1) injections. No differences in mean residence
      time (9.7 +/- 4.9 and 8.4 +/- 2.7 h) or terminal half-life (8.5 +/- 3.8 and 7.5
      +/- 2.3 h) were observed. Teicoplanin penetrated mediastinal and heart tissues
      but not sternal bone, where the antibiotic was detectable in only 1 of 13
      patients in group 1 and 2 of 10 patients in group 2. In group 1, 7 of 13 patients
      had teicoplanin concentrations in tissue that were lower than the MIC for 90% of
      the strains of potential pathogens tested (MIC90) that cause infection after
      cardiac surgery. All of the patients in group 2 but one had teicoplanin
      concentrations in tissue (other than in sternal bone) far in excess of the MIC90
      for the potential pathogens. In conclusion, the 12-mg x kg(-1) regimen of
      teicoplanin is followed by a significant increase in teicoplanin concentrations
      in heart and mediastinal tissues and should be preferred to the 6-mg x kg(-1)
      regimen if teicoplanin is selected for antimicrobial prophylaxis in open heart
      surgery.

PMID- 9145888
TI  - In vitro activity of a new echinocandin, LY303366, compared with those of
      amphotericin B and fluconazole against clinical yeast isolates.
AB  - The in vitro activity of LY303366, a new echinocandin derivative, was evaluated
      with 191 yeast isolates by a broth microdilution method. The MICs at which 50% of
      the isolates were inhibited were 0.125 microg/ml for Candida albicans and C.
      tropicalis, 0.25 microg/ml for C. krusei, C. kefyr, and C. glabrata, and 2.0
      microg/ml for C. parapsilosis.

PMID- 9145889
TI  - Susceptibility to beta-lactam antibiotics of Pseudomonas aeruginosa overproducing
      penicillin-binding protein 3.
AB  - By using a broad-host-range vector, pUCP27, the Pseudomonas aeruginosa and
      Escherichia coli pbpB genes, which encode penicillin-binding protein 3 (PBP3),
      were separately overexpressed in a P. aeruginosa strain, PAO4089, that is
      deficient in producing chromosomal beta-lactamase. Susceptibility studies
      indicated that overproduction of the P. aeruginosa PBP3 in PAO4089 resulted in
      twofold-increased resistance to aztreonam, fourfold-increased resistance to
      cefepime and cefsulodin, and eightfold-increased resistance to ceftazidime,
      whereas overproduction of the P. aeruginosa PBP3 in PAO4089 did not affect
      susceptibility to PBP1-targeted cephaloridine or PBP2-targeted imipenem. Similar
      results were obtained with PAO4089 overproducing E. coli PBP3, with the exception
      that there was no influence on the MICs or minimal bactericidal concentrations of
      cefsulodin and cefepime, which have very low affinities for E. coli PBP3. These
      data are consistent with the conclusion that PBP3 has to achieve a certain level
      of saturation, with beta-lactams targeted to this protein, to result in cell
      inhibition or death.

PMID- 9145890
TI  - Clinical resistance to erythromycin and clindamycin in cutaneous propionibacteria
      isolated from acne patients is associated with mutations in 23S rRNA.
AB  - The genetic basis of erythromycin resistance in cutaneous propionibacteria was
      determined by comparing the nucleotide sequences of the peptidyl transferase
      region in the 23S rRNAs from 9 susceptible and 26 resistant clinical isolates as
      well as 4 laboratory-selected erythromycin-resistant mutants of a susceptible
      strain. In 13 isolates and the 4 laboratory mutants, cross-resistance to
      macrolides, lincosamides, and B-type streptogramins was associated with an A-->G
      transition at a position cognate with Escherichia coli 23S rRNA base 2058. These
      strains were resistant to > or = 512 microg of erythromycin per ml. Two other
      mutations were identified, an A-->G transition at base 2059 in seven strains,
      associated with high-level resistance to all macrolides, and a G-->A transition
      at base 2057 in six strains, associated with low-level resistance to
      erythromycin. These mutations correspond to three of four phenotypic classes
      previously identified by using MIC determinations.

PMID- 9145891
TI  - Characterization of a mutation in the parE gene that confers fluoroquinolone
      resistance in Streptococcus pneumoniae.
AB  - We report a mutation in the parE genes of two in vitro mutants of Streptococcus
      pneumoniae responsible for low-level resistance to fluoroquinolones. Sequential
      acquisition of mutations in parE and gyrA leads to higher levels of resistance.
      This confirms that topoisomerase IV is the primary target of fluoroquinolones in
      S. pneumoniae.

PMID- 9145892
TI  - Comparative activities of amikacin against Mycobacterium avium complex in nude
      and beige mice.
AB  - After 4 weeks of treatment, clarithromycin (CLAR) and amikacin showed similar
      antimicrobial activities against the Mycobacterium avium complex in mice. There
      was a difference, however, in the effectiveness of the drugs in different types
      of mice: both drugs displayed bactericidal effects in beige mice but only
      bacteriostatic effects in nude mice. Because the effectiveness of CLAR is less in
      nude mice than in beige mice, the predictive value of the nude mouse model for
      the efficacy of chemotherapy is less than that of the beige mouse model.

PMID- 9145893
TI  - Postantibiotic effect assessments for antibiotics exhibiting a wide range of
      bactericidal activities by using a modified total-cell-counting method.
AB  - We recently described a total-cell-counting method for postantibiotic effect
      (PAE) assessments that performs well with weakly bactericidal antibiotics. This
      note presents a modified method for the study of PAE with extended capability to
      cover a broad range of bactericidal activities.

PMID- 9145894
TI  - Ampicillin susceptibilities of vaginal and placental isolates of group B
      streptococcus and Escherichia coli obtained between 1992 and 1994.
AB  - Vaginal group B streptococcus (GBS) and Escherichia coli isolates were tested for
      their susceptibilities to ampicillin. All 414 GBS isolates tested were
      susceptible to ampicillin; the MIC at which 90% of the isolates were inhibited
      (MIC90) was 0.125 microg/ml, and the range was 0.06 to 0.25 microg/ml. The MIC50
      for the 342 E. coli isolates tested was 4.0 microg/ml, and 27% were resistant to
      ampicillin.

PMID- 9145897
TI  - Cloning and sequence analysis of a class A beta-lactamase from Mycobacterium
      tuberculosis H37Ra.
AB  - A cosmid library from Mycobacterium tuberculosis H37Ra was introduced into
      Mycobacterium smegmatis, and eight recombinant clones with increased resistance
      to cefoxitin were identified. Isoelectric focusing detected an M. tuberculosis
      derived beta-lactamase in one of these recombinant clones. A sequence analysis
      identified it as a class A beta-lactamase whose expression correlated with the
      increased resistance phenotype.

PMID- 9145895
TI  - Lack of ability of ciprofloxacin-rifampin prophylaxis to decrease infection
      related morbidity in neutropenic patients given cytotoxic therapy and peripheral
      blood stem cell transplants.
AB  - We compared ciprofloxacin alone with ciprofloxacin plus rifampin (C + R) as a
      prophylactic antibacterial regimen for 40 patients with solid tumors treated with
      high-dose chemotherapy and autologous stem cell transplantation support. No
      differences were found between groups in the time elapsed to the onset of fever,
      incidence of febrile episodes, amphotericin B use, and length of hospital stay.
      However, C + R combination prophylaxis significantly reduced the incidence of
      gram-positive bacteremia (five versus zero episodes) but was associated with a
      higher incidence of drug-related side effects.

PMID- 9145896
TI  - Efficacies of ofloxacin, rifampin, and clindamycin in treatment of Staphylococcus
      aureus abscesses and correlation with results of an in vitro assay of
      intracellular bacterial killing.
AB  - We studied the efficacies of ofloxacin, rifampin, and clindamycin in a
      Staphylococcus aureus abscess model and seven antimicrobial regimens in an
      intracellular killing assay. Ofloxacin plus rifampin was the most effective
      regimen in the abscess model, and rifampin and ofloxacin were the most active
      regimens in the intracellular killing assay.

PMID- 9145898
TI  - Trovafloxacin in treatment of rabbits with experimental meningitis caused by high
      level penicillin-resistant Streptococcus pneumoniae.
AB  - The fluoroquinolone trovafloxacin was bactericidal (0.47 +/- 0.23 delta log10
      CFU/ml x h after 10 mg/kg of body weight and 0.78 +/- 0.15 delta log10 CFU/ml x h
      after 30 mg/kg) in the treatment of experimental meningitis caused by a highly
      penicillin-resistant (MIC and minimum bactericidal concentration = 4 and 4
      microg/ml) strain of Streptococcus pneumoniae. Combinations with ampicillin and
      rifampin were indifferent compared to single drugs.

PMID- 9145899
TI  - In vitro activity of premafloxacin, a new extended-spectrum fluoroquinolone,
      against pathogens of veterinary importance.
AB  - The in vitro activity of premafloxacin against 673 veterinary pathogens was
      evaluated. Premafloxacin was equivalent to ciprofloxacin, enrofloxacin, and
      danofloxacin in activity against the gram-negative bacilli but was much more
      active (MIC for 90% of the strains tested [MIC90], 0.015 to 0.25 microg/ml) than
      the comparison antimicrobial agents (MIC90, 0.13 to 16.0 microg/ml) against the
      staphylococci, streptococci, and anaerobes tested.

PMID- 9145901
TI  - In vitro activity of RU 64004, a new ketolide antibiotic, against gram-positive
      bacteria.
AB  - The comparative in vitro activity of RU 64004 (also known as HMR 3004), a new
      ketolide antibiotic, was tested by agar dilution against approximately 500 gram
      positive organisms, including multiply resistant enterococci, streptococci, and
      staphylococci. All streptococci were inhibited by < or = 1 microg of RU 64004 per
      ml. The ketolide was more potent than other macrolides against erythromycin A
      susceptible staphylococci and was generally more potent than clindamycin against
      erythromycin A-resistant strains susceptible to this agent. Clindamycin-resistant
      staphylococci (MIC, > 128 microg/ml) proved resistant to the ketolide, but some
      erythromycin A- and clindamycin-resistant enterococci remained susceptible to RU
      64004.

PMID- 9145900
TI  - Comparative in vitro activities of DU-6859a, levofloxacin, ofloxacin,
      sparfloxacin, and ciprofloxacin against 387 aerobic and anaerobic bite wound
      isolates.
AB  - The activities of DU-6859a, levofloxacin, ofloxacin, sparfloxacin, and
      ciprofloxacin against bite wound isolates were determined by the agar dilution
      method. DU-6859a was the most active compound (MICs, < or = 0.125 microg/ml)
      against all Pasteurella species, Staphylococcus aureus, and streptococci;
      anaerobes were susceptible to < or = 0.5 microg/ml, except fusobacteria, which
      were susceptible to < or = 2 microg/ml. Against aerobes, levofloxacin was more
      active than ofloxacin (MIC at which 90% of isolates are inhibited [MIC90], < or =
      1.0 microg/ml for both) and sparfloxacin and ciprofloxacin were also active
      (MIC90s, < or = 0.25 and < 1 microg/ml, respectively).

PMID- 9145903
TI  - A bla(TEM-1b)-derived TEM-6 beta-lactamase: a case of convergent evolution.

PMID- 9145902
TI  - Essential role of endogenously synthesized tylosin for induction of ermSF in
      Streptomyces fradiae.
AB  - We compared ermSF induction in wild-type Streptomyces fradiae NRRL B-2702 and
      that in GS-14, a tylA mutant which cannot synthesize tylosin. Our findings
      suggest that (i) endogenously synthesized tylosin plays an obligatory role in
      ermSF induction and (ii) tylosin, or a biosynthetic intermediate beyond
      tylactone, has an "autocrine" function that induces ErmSF synthesis, thereby
      enabling S. fradiae to resist higher levels of tylosin.

PMID- 9145904
TI  - Ergotism related to concurrent administration of ergotamine tartrate and
      ritonavir in an AIDS patient.

PMID- 9145905
TI  - In vitro susceptibility testing of Borrelia burgdorferi by a dialysis culture
      method.

PMID- 9145906
TI  - Penicillin resistance in Veillonella.

PMID- 9145907
TI  - Noncoplanar PCB 95 alters microsomal calcium transport by an immunophilin FKBP12
      dependent mechanism.
AB  - Ortho-substituted polychlorinated biphenyls (PCBs) have been shown to alter
      microsomal Ca2+ transport by selective interaction with ryanodine receptors
      (RyRs) of muscle sarcoplasmic reticulum (SR) and brain endoplasmic reticulum. The
      mechanism underlying the actions of PCBs on Ca2+ transport is further elucidated
      with skeletal SR enriched in Ry1R. Disruption of the association between
      immunophilin FKBP12 and Ry1R with FK 506 or rapamycin completely eliminates PCB
      95-enhanced binding of [3H]ryanodine (IC50 approximately 35 microM) to Ry1R and
      PCB 95-induced release of Ca2+ from actively loaded SR vesicles (IC50
      approximately 11 microM), demonstrating a FKBP12-dependent mechanism. FK 506
      selectively eliminates PCB 95-induced Ca2+ release from SR because Ry1R maintains
      responsiveness to caffeine and Ca2+. PCB 95 and FK 506 are used to examine the
      relationship between ryanodine-sensitive Ca2+ channels and ryanodine-insensitive
      Ca2+ leak pathways present in SR vesicles. Micromolar ryanodine completely blocks
      ryanodine-sensitive Ca2+ efflux but neither eliminates the ryanodine-insensitive
      Ca2+ leak unmasked by thapsigargin nor enhances the loading capacity of SR
      vesicles. PCB 95 alone enhances thapsigargin evoked Ca2+ release and therefore
      diminishes the loading capacity of SR vesicles. However, in the presence of
      micromolar ryanodine, PCB 95 dose-dependently eliminates the Ca2+ leak unmasked
      by thapsigargin and significantly enhances the loading capacity of SR vesicles.
      The actions of PCB 95 on SR-loading capacity are additive with those of FK 506.
      Structural specificity for these novel actions are further demonstrated with
      coplanar PCB 126, which is inactive toward Ry1R and lacks the ability to alter
      the Ca2+ leak pathway. The results reveal that FKBP12 relates ryanodine
      insensitive Ca2+ "leak" and ryanodine-sensitive Ca2+ channel efflux pathways of
      SR by modulating distinct conformations Ry1R complexes. Noncoplanar PCBs, like
      PCB 95, alter SR Ca2+ buffering by an FKBP12-mediated mechanism. An immunophilin
      based mechanism could account for the toxic actions attributed to certain
      noncoplanar PCB congeners.

PMID- 9145909
TI  - Subtype-specific intracellular trafficking of alpha2-adrenergic receptors.
AB  - The three alpha2-adrenergic receptor subtypes (alpha2a, alpha2b, and alpha2c) are
      highly homologous G protein-coupled receptors. These receptors all couple to
      pertussis toxin-sensitive G proteins and have relatively similar pharmacological
      properties. To further explore functional differences between these receptors, we
      used immunocytochemical techniques to compare the ability of the three alpha2
      receptor subtypes to undergo agonist-mediated internalization. The alpha2a
      receptor does not internalize after agonist treatment. In contrast, we observed
      that the alpha2b-receptor is able to undergo agonist-induced internalization and
      seems to follow the same endosomal pathway used by the beta2-adrenergic receptor.
      Attempts to examine internalization of the alpha2c-receptor were complicated by
      the fact that the majority of the alpha2c receptor resides in the endoplasmic
      reticulum and cis/media Golgi and there is relatively little cell surface
      localization. Nevertheless, we were able to detect some internalization of the
      alpha2c-receptor after prolonged agonist treatment. However, we observed no
      significant movement of alpha2c-receptor from the intracellular pool to the
      plasma membrane during a 4-hr treatment of cells with cycloheximide, suggesting
      that these cells are unable to process alpha2c-receptors in the same way they
      process the alpha2a or alpha2b subtypes.

PMID- 9145908
TI  - Effect of transforming growth factor-beta1 on expression of aryl hydrocarbon
      receptor and genes of Ah gene battery: clues for independent down-regulation in
      A549 cells.
AB  - An inhibitory effect on both constitutive and inducible expression of cytochrome
      P450 isoenzymes has been shown for different cytokines and growth factors. We
      previously described an inhibition of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      induced CYP1A1 mRNA and enzyme activity by transforming growth factor-beta1 (TGF
      beta1) in human lung cancer A549 cells. In the present study, we report that not
      only TCDD-induced expression of CYP1A1 but also basal mRNA expression of CYP1A1,
      CYP1B1, and aryl hydrocarbon receptor (AHR) was down-regulated by TGF-beta1 in
      cells not treated with TCDD. In contrast, mRNA expression of the AHR partner
      protein Arnt (aryl hydrocarbon receptor nuclear translocator) was not influenced.
      Furthermore, TCDD-induced expression of CYP1B1 and NMO-1 was inhibited, and the
      IC50 values of 5-10 pM TGF-beta1 were in the same range as observed for
      inhibition of CYP1A1 and AHR mRNA expression. Transfection studies with a plasmid
      containing a luciferase reporter gene under control of two dioxin-responsive
      elements indicate an effect on AHR protein expression. Results of time-course
      studies revealed a parallel inhibition of AHR and CYP1 mRNA expression,
      indicating that TGF-beta1 is a direct negative regulator of transcription of
      these genes. The treatment of cells with cycloheximide led to a superinduction of
      TCDD-induced CYP1A1 and CYP1B1 mRNA expression and abolished the inhibitory
      effect of TGF-beta1 on basal as well as TCDD-induced CYP1 and AHR mRNA
      expression. TGF-beta1 seems not to influence the stability of AHR mRNA. The
      results suggest that TGF-beta1 induces rapid transcription and translation of an
      as-yet-unknown negative regulatory factor or factors that may directly regulate
      expression of AHR and genes of Ah gene battery.

PMID- 9145910
TI  - Effect of gastrin-releasing peptide receptor number on receptor affinity,
      coupling, degradation, and modulation.
AB  - The relationship between receptor number and agonist-induced intracellular
      responses has been well studied in receptors coupled to adenylate cyclase;
      however, for receptors coupled to phospholipase C (PLC), very little is known
      about the effect of receptor number on receptor-mediated processes. To explore
      this issue, we investigated the effect of the number of receptors for gastrin
      releasing peptide (GRP) on ligand affinity and on the ability to activate
      intracellular messengers [PLC, tyrosine phosphorylation of p125 focal adhesion
      kinase (p125FAK)] and cause receptor modulation (internalization,
      desensitization, down-regulation) and ligand degradation. Three BALB 3T3 cell
      lines were made that stably expressed the gastrin-releasing peptide receptor (GRP
      R) with receptor numbers varying by 280-fold (GRP-R-Low, GRP-R-Med, and GRP-R
      Hi). Each cell line had the same affinity for agonist. The efficacy for bombesin
      to increase [3H]inositol phosphates but not tyrosine phosphorylation of p125FAK
      correlated well with receptor number. In contrast, the EC50 value for
      [3H]inositol phosphate generation for bombesin was the same in each cell line.
      Receptor number did not alter internalization. In the absence of protease
      inhibitors, there was an inverse correlation between receptor number and receptor
      down-regulation and desensitization. However, with protease inhibitors present,
      GRP-R-Med and GRP-R-Hi down-regulated significantly less than the GRP-R-Low.
      Similarly, GRP-R-Low desensitized significantly more than GRP-R-Med or GRP-R-Hi.
      GRP-R-Hi caused significantly greater ligand degradation than GRP-R-Low, and
      protease inhibitors completely inhibited degradation by GRP-R-Low and inhibited
      degradation by 70% for GRP-R-Hi. In conclusion, we show that for the PLC-coupled
      GRP-R, receptor number had little or no effect on binding affinity, potency for
      activating PLC, tyrosine phosphorylation of p125FAK, or extent of receptor
      internalization. In contrast, receptor number had an effect on ligand
      degradation, down-regulation, desensitization, and efficacy of PLC activation
      without altering the efficacy of tyrosine phosphorylation of p125FAK. These
      results demonstrate that the effect of receptor number differs for the different
      functions mediated by the GRP receptor and differs from that reported for
      adenylate cyclase-coupled receptors such as receptors mediating the action of
      adrenergic agents, secretin, and opioids.

PMID- 9145911
TI  - Chronic ethanol increases N-methyl-D-aspartate-stimulated nitric oxide formation
      but not receptor density in cultured cortical neurons.
AB  - The effects of prolonged ethanol exposure on excitatory amino acid receptor
      stimulated nitric oxide (NO) formation were examined in primary rat cortical
      neuronal cultures. Chronic ethanol (4 days, 100 mM) potentiated N-methyl-D
      aspartate (NMDA)-stimulated NO formation as determined by measuring the
      conversion of [3H]arginine to [3H]citrulline. In contrast, chronic ethanol had no
      effect on NO formation stimulated by kainate, alpha-amino-3-hydroxy-5-methyl-4
      isoxalonepropionic acid, or the calcium ionophore ionomycin. Potassium chloride
      stimulated NO formation was also enhanced by chronic ethanol treatment, but this
      effect was not seen in the presence of the ionotropic glutamate receptor
      antagonists MK-801 and 6-cyano-7-nitroquinoxaline-2,3-dione. Immunoblot analysis
      of expression of NR1, NR2A, and NR2B receptor subunits showed no difference
      between control and chronic ethanol-treated cultures. In support of this apparent
      lack of change in receptor density, there was no difference in the specific
      binding of 125I-MK-801 between control and chronic ethanol-treated groups. These
      results demonstrate that prolonged ethanol exposure selectively enhanced NMDA
      receptor-stimulated NO formation, which may play an important role in alcohol
      dependence, withdrawal, and alcohol-associated brain damage. These results also
      suggest that chronic ethanol-induced increases in NMDA receptor function may not
      be due to a simple increase in the number of NMDA receptors or change in NMDA
      receptor subunit composition but may instead reflect more complicated and subtle
      changes.

PMID- 9145912
TI  - Expression of enzymatically active CYP3A4 by Caco-2 cells grown on extracellular
      matrix-coated permeable supports in the presence of 1alpha,25-dihydroxyvitamin
      D3.
AB  - The human colon carcinoma cell line, Caco-2, is widely used as a model for oral
      absorption of xenobiotics. The usefulness of Caco-2 cells has been limited,
      however, because they do not express appreciable quantities of CYP3A4, the
      principle cytochrome P450 present in human small bowel epithelial cells. We
      report that treatment of Caco-2 cells with 1 alpha,25-dihydroxyvitamin D3,
      beginning at confluence, results in a dose- and duration-dependent increase in
      CYP3A4 mRNA and protein, with little apparent effect on the expression of CYP3A5
      or CYP3A7. This treatment also results in increases in NADPH cytochrome P450
      reductase and P-glycoprotein (the MDR1 gene product) but has no detectable effect
      on expression of CYP1A1, CYP2D6, cytochrome b5, liver or intestinal fatty acid
      binding proteins, or villin. Maximal expression of CYP3A4 requires an
      extracellular matrix on a permeable support and the presence of serum. In the
      treated cells, the intrinsic formation clearance of 1'-hydroxymidazolam (a
      reaction characteristically catalyzed by CYP3A enzymes) was estimated to be
      somewhat lower than that of human jejunal mucosa (1.14 and 3.67 ml/min/g of
      cells, respectively). The 1'-OH-midazolam/4-OH-midazolam product ratio produced
      by the cells (approximately 5.3) is comparable to, but somewhat lower than, that
      observed in human jejunal microsomes (7.4-15.4), which may reflect the presence
      of CYP3A7 in the Caco-2 cells. 25-Hydroxyvitamin D3 is less efficacious but
      reproduces the effects of the dihydroxy compound, whereas unhydroxylated vitamin
      D is without appreciable effect. These observations, together with the time
      course of response, suggest that the vitamin D receptor may be involved in CYP3A4
      regulation. The culture model we describe should prove useful in defining the
      role of CYP3A4 in limiting the oral bioavailability of many xenobiotics.

PMID- 9145913
TI  - 5-Hydroxytryptamine1B receptors modulate the effect of cocaine on c-fos
      expression: converging evidence using 5-hydroxytryptamine1B knockout mice and the
      5-hydroxytryptamine1B/1D antagonist GR127935.
AB  - Serotonergic transmission has been suggested to modulate the effects of cocaine.
      However, the specific receptors and brain structures underlying this phenomenon
      have not been identified. To test the possible contribution of the 5
      hydroxytryptamine1B (5-HT1B) receptor, we studied the induction of the immediate
      early gene c-fos elicited by cocaine in knockout mice lacking this receptor. 5
      HT1B knockout mice display a markedly reduced effect of cocaine on c-fos
      induction in different brain structures, most notably in the striatum. In
      addition, the administration to wild-type mice of the 5-HT1B receptor agonist
      RU24969 results in a striatal induction of c-fos expression very similar to that
      induced by cocaine in its time course, cellular and anatomical distribution, and
      pharmacology. Here, we also report the ability of a 5-HT1D receptor antagonist,
      GR127935, to antagonize 5-HT1B receptors in vivo. Finally, when administered to
      wild-type mice, GR127935 reduces the increase in striatal c-fos expression
      elicited by cocaine. These converging lines of evidence obtained with the
      knockout mice and 5-HT(1B/1D) antagonist indicate that cocaine acts as an
      indirect agonist of 5-HT1B receptors in vivo and demonstrate that activation of 5
      HT1B receptors contributes to the cellular responses elicited by cocaine.

PMID- 9145914
TI  - Alpha1D-adrenergic receptors and mitogen-activated protein kinase mediate
      increased protein synthesis by arterial smooth muscle.
AB  - Catecholamines may influence vascular smooth muscle cell (SMC) growth and
      vascular hypertrophic diseases. We previously demonstrated that stimulation of
      alpha1-adrenoceptors (AR) causes hypertrophy of vascular SMCs in vitro and in
      situ. Here, we used adult rat aorta SMCs that express alpha1D- and alpha1B-ARs
      (but not alpha1A-ARs) in vitro to examine the mechanisms and alpha1-AR subtypes
      involved. Norepinephrine (NE) increased protein synthesis and content in a time-
      and dose-dependent manner. To identify the responsible alpha1-AR subtype, we
      first documented the selectivity of two alpha1-AR subtype antagonists, BMY 7378
      (alpha1D-AR antagonist) and chloroethylclonidine (CEC; alpha1B-AR antagonist),
      using Rat-1 fibroblasts stably transfected with the three different rodent alpha1
      AR cDNAs. NE dose-dependently increased protein synthesis in each cell line. In
      alpha1D fibroblasts, BMY 7378 inhibited growth and protected alpha1D-ARs from CEC
      alkylation while having little blocking or protecting effect on the growth
      induced by stimulation of fibroblasts that express alpha1A- or alpha1B-ARs. In
      rat aorta SMCs, pretreatment with CEC in the presence of BMY 7378 to protect
      alpha1D-ARs had no effect on NE-induced protein synthesis. BMY 7378 inhibited the
      SMC growth response with a pKb of 8.4. NE caused rapid and transient p42-p44
      mitogen-activated protein kinase (MAPK) activation that was alpha1D-AR dependent.
      Furthermore, NE caused tyrosine phosphorylation of multiple cellular proteins,
      phosphorylation of Raf-1, and stimulation of c-fos mRNA expression in aorta SMCs.
      The selective MAPK kinase inhibitor PD 98059 inhibited NE-induced protein
      synthesis and MAPK activation with IC50 values of 2.3 and 1.6 microM,
      respectively. These data demonstrate that SMC growth induced by NE is mediated by
      alpha1D-ARs that couple to activation of the MAPK cascade.

PMID- 9145915
TI  - Chronic nicotine treatment up-regulates alpha3 and alpha7 acetylcholine receptor
      subtypes expressed by the human neuroblastoma cell line SH-SY5Y.
AB  - Chronic exposure to nicotine has been reported to increase the number of
      nicotinic acetylcholine receptors (AChRs) in brain. The mechanism of up
      regulation for the alpha4beta2 AChR subtype, which accounts for the majority of
      high affinity nicotine binding in mammalian brain, has previously been shown to
      involve a decrease in the rate of alpha4beta2 AChR turnover. Here, we report an
      investigation of the extent and mechanism of nicotine-induced up-regulation of
      alpha3 AChRs and alpha7 AChR subtypes expressed in the human neuroblastoma cell
      line SH-SY5Y. Up-regulation of human alpha3 AChRs and alpha7 AChRs, unlike
      alpha4beta2 AChRs, requires much higher nicotine concentrations than are
      encountered in smokers; the extent of increase of surface AChRs is much less; and
      the mechanisms of up-regulation are different than with alpha4beta2 AChRs. The
      mechanisms of up-regulation may be different for alpha3 AChRs or alpha7 AChRs.
      Chronic treatment with nicotine or carbamylcholine, but not d-tubocurarine,
      mecamylamine, or dihydro-beta-erythroidine, induced a 500-600% increase in the
      number of alpha3 AChRs but only a 30% increase in alpha7 AChRs. Chronic nicotine
      treatment did not increase affinity for nicotine or increase the amount of RNA
      for alpha3 or alpha7 subunits. The effect of nicotine on up-regulation of alpha7
      AChRs was partially blocked by either d-tubocurarine or mecamylamine. The effect
      of nicotine treatment on the number of alpha3 AChRs was only slightly blocked by
      the antagonists d-tubocurarine, mecamylamine, or dihydro-beta-erythroidine at
      concentrations that efficiently block alpha3 AChR function. Most of the nicotine
      induced increase in alpha3 AChRs was found to be intracellular. The alpha3 AChRs,
      which accumulate intracellularly, were shown to have been previously exposed on
      the cell surface by their susceptibility to antigenic modulation. The data
      suggest that chronic exposure to nicotine may induce a conformation of cell
      surface alpha3 AChRs that at least in this cell line are consequently
      internalized but not immediately destroyed.

PMID- 9145916
TI  - Effect of cell type on the subcellular localization of the thyrotropin-releasing
      hormone receptor.
AB  - The localization of an epitope-tagged receptor for thyrotropin-releasing hormone
      (TRH) expressed in different cell contexts was studied with immunofluorescence
      microscopy. In pituitary lactotrophs, which normally express TRH receptors, and
      in AtT20 pituitary corticotrophs, TRH receptor immunoreactivity was primarily
      confined to the plasma membrane. In HEK 293 and COS7 cells, TRH receptors were
      predominantly intracellular. In transiently transfected COS7 cells, the TRH
      receptor colocalized with endoplasmic reticulum and Golgi markers. The pattern of
      TRH receptor immunofluorescence was the same over a wide range of receptor
      expression in transiently transfected COS7 cells, and all cell lines bound
      similar amounts of 3H- and rhodamine-labeled TRH analogs, suggesting that cell
      specific differences in TRH receptor localization were not simply the result of
      overexpression. In all cell contexts, TRH receptors on the plasma membrane
      underwent extensive ligand-driven endocytosis. Inhibitors of glycosylation did
      not alter the subcellular distribution of receptors. In HEK 293 cells expressing
      the transfected TRH receptor, protein synthesis inhibitors caused translocation
      of intracellular receptors to the cell surface, as shown by a marked increase in
      cell surface immunofluorescence and [3H][N3-methyl-His2]TRH binding. These
      results demonstrate that the subcellular localization of the TRH receptor depends
      on the cell context in which it is expressed and that intracellular receptors are
      capable of translocation to the plasma membrane.

PMID- 9145917
TI  - Glucocorticoid regulation of corticotropin-releasing factor1 receptor expression
      in pituitary-derived AtT-20 cells.
AB  - Corticotropin-releasing factor (CRF) receptors represent one of the primary sites
      for negative feedback of the pituitary by adrenocortical glucocorticoid hormones;
      however, the molecular mechanisms involved have yet to be elucidated. The present
      study examines the mechanisms by which glucocorticoids regulate CRF-R1 expression
      in the pituitary cell line, AtT-20. Treatment of these cells with dexamethasone
      resulted in a concentration- and time-dependent inhibition of CRF-R1 mRNA that
      was significant by 1 hr and maximal after 4 hr. Levels of CRF-R1 mRNA then
      returned to control levels after 24 hr. Similar changes were observed when the
      cells were treated with corticosterone. Pro-opiomelanocortin mRNA was also
      decreased after dexamethasone pretreatment; however, the time course was much
      slower with a significant effect only detected after 6 hr. Further analysis of
      the mechanisms that mediate glucocorticoid regulation of CRF-R1 mRNA was
      conducted These studies demonstrated that glucocorticoid incubation significantly
      decreases the rate of CRF-R1 gene transcription, as determined by nuclear run-on
      analysis. In addition, the result demonstrate that glucocorticoid incubation
      significantly decreases CRF-R1 mRNA stability by approximately 50%. The down
      regulation of CRF-R1 mRNA was dependent on de novo protein synthesis, as it was
      blocked by pretreatment with cycloheximide. This represents a novel mechanism for
      glucocorticoid negative feedback regulation of CRF-R1 expression.

PMID- 9145918
TI  - Synergistic regulation of beta2-adrenergic receptor sequestration: intracellular
      complement of beta-adrenergic receptor kinase and beta-arrestin determine
      kinetics of internalization.
AB  - Two of the common mechanisms regulating G protein-coupled receptor (GPCR) signal
      transduction are phosphorylation and sequestration (internalization). Agonist
      mediated receptor phosphorylation by the beta-adrenergic receptor kinase
      (betaARK) facilitates subsequent interaction with an arrestin protein, resulting
      in receptor desensitization. Studies of the beta2-adrenergic receptor (beta2AR)
      receptor in human embryonic kidney (HEK) 293 cells indicate that betaARK and
      arrestin proteins (beta-arrestins) also regulate sequestration. Consistent with
      this notion, we show in HEK 293 cells that reduction in or removal of the ability
      of the beta2AR to be phosphorylated by betaARK or to interact normally with beta
      arrestin substantially reduces agonist-mediated sequestration. To evaluate
      betaARK and beta-arrestin regulation of beta2AR sequestration, we examined the
      relationship between betaARK and/or beta-arrestin expression and beta2AR
      sequestration in a variety of cultured cells, including HEK 293, COS 7, CHO,
      A431, and CHW. COS cells had both the lowest levels of endogenous beta-arrestin
      expression and beta2AR sequestration, whereas HEK 293 had the highest.
      Overexpression of beta-arrestin, but not betaARK, in COS cells increased the
      extent of wild-type beta2AR sequestration to levels observed in HEK 293 cells.
      However, a betaARK phosphorylation-impaired beta2AR mutant (Y326A) required the
      simultaneous overexpression of both betaARK and beta-arrestin for this to occur.
      Among all cell lines, sequestration correlated best with the product of betaARK
      and beta-arrestin expression. Moreover, an agonist-mediated translocation of wild
      type beta2AR and endogenous beta-arrestin 2 to endocytic vesicles prepared from
      CHO fibroblasts was observed. These data suggest not only that the complement of
      cellular betaARK and arrestin proteins synergistically regulate beta2AR
      sequestration but also that beta-arrestins directly regulate beta2AR trafficking
      as well as desensitization.

PMID- 9145919
TI  - Contrasting modes of action of methylglutamate derivatives on the excitatory
      amino acid transporters, EAAT1 and EAAT2.
AB  - We have investigated the mechanism of action of a series of glutamate derivatives
      on the cloned excitatory amino acid transporters 1 and 2 (EAAT1 and EAAT2),
      expressed in Xenopus laevis oocytes. The compounds were tested as substrates and
      competitive blockers of the glutamate transporters. A number of compounds showed
      contrasting mechanisms of action on EAAT1 compared with EAAT2. In particular,
      (2S,4R)-4-methylglutamate and 4-methylene-glutamate were transported by EAAT1,
      with Km values of 54 microM and 391 microM, respectively, but potently blocked
      glutamate transport by EAAT2, with Kb values of 3.4 microM and 39 microM,
      respectively. Indeed, (2S,4R)-4-methylglutamate is the most potent blocker of
      EAAT2 yet described. (+/-)-Threo-3-methylglutamate also potently blocked
      glutamate transport by EAAT2 (Kb = 18 microM), but was inactive on EAAT1 as
      either a substrate or a blocker at concentrations up to 300 microM. In contrast
      to (2S,4R)-4-methylglutamate, L-threo-4-hydroxyglutamate was a substrate for both
      EAAT1 and EAAT2, with Km values of 61 microM and 48 microM, respectively. It
      seems that the chemical nature and also the orientation of the group at the 4
      position of the carbon backbone of glutamate is crucial in determining the
      pharmacological activity. The conformations of these molecules have been modeled
      to understand the structural differences between, firstly, compounds that are
      blockers versus substrates of EAAT2 and, secondly, the pharmacological
      differences between EAAT1 and EAAT2.

PMID- 9145920
TI  - Interaction of [3H]orphanin FQ and 125I-Tyr14-orphanin FQ with the orphanin FQ
      receptor: kinetics and modulation by cations and guanine nucleotides.
AB  - The heptadecapeptide orphanin FQ (OFQ) has been identified as the endogenous
      ligand for a G protein-coupled receptor (OFQ-R), which, despite its high degree
      of sequence similarity to opioid receptors, fails to bind opioid ligands. We
      developed two radioligands for the OFQ-R: a tritiated native OFQ peptide
      ([3H]OFQ) and a radioiodinated form in which Leu14 was substituted by tyrosine
      (125I-Tyr14-OFQ). Their binding properties were examined in human embryonic
      kidney (HEK) 293 and Chinese hamster ovary (CHO) cells heterologously expressing
      the OFQ-R at different levels (HEK 293 expressed 40-fold more OFQ-R than did
      CHO). Both ligands exhibited rapid, monophasic association kinetics in each cell
      line. Dissociation of both ligands from OFQ-R expressed in HEK 293 cells was
      biphasic, whereas dissociation of 125I-Tyr14-OFQ from OFQ-R expressed in CHO
      cells was monophasic and slow. Saturation binding analysis revealed two affinity
      states in HEK 293 cells with binding parameters in accord with those determined
      kinetically. In CHO cells, 125I-Tyr14-OFQ detected a single affinity state with
      an intermediate Kd value of 54 pM. Optimal binding of the radioligands required 1
      5 mM MgCl2, whereas millimolar concentrations of ZnCl2, CaCl2, MnCl2, and NaCl
      reduced specific binding of both ligands. A nonhydrolyzable GTP analog [guanosine
      5'-(beta,gamma-imido)triphosphate] reduced the affinity of both OFQ ligands to
      their receptor without significant changes in the total binding capacity,
      indicating functional interactions between the OFQ-R and G proteins. In rat brain
      membranes, specific, saturable binding of 125I-Tyr14-OFQ was demonstrated to be
      pharmacologically identical to the heterologously expressed OFQ-R. Taken
      together, these results indicate that 125I-Tyr14-OFQ and [3H]OFQ exhibit
      virtually identical characteristics and are suitable for the pharmacological
      analysis of the OFQ-R.

PMID- 9145921
TI  - gamma-Glutamyl hydrolase from human sarcoma HT-1080 cells: characterization and
      inhibition by glutamine antagonists.
AB  - Elevated gamma-glutamyl hydrolase (GGH) activity as a contributing factor in
      mechanisms of acquired and intrinsic antifolate resistance has been reported for
      several cultured cell lines. Despite this, little is known about this enzyme,
      especially the human species. Using the human HT-1080 sarcoma line, we observed
      the secretion of GGH activity into media during culture (a phenomenon that could
      be markedly stimulated by exposure to NH4Cl) and an acidic pH optimum for in
      vitro catalytic activity of the enzyme. These properties are consistent with a
      lysosomal location for the enzyme. Unlike rodent GGH, preparations of HT-1080
      enzyme (purified < or = 2000-fold) displayed exopeptidase activity in cleaving
      successive end-terminal gamma-glutamyl groups from poly-L-gamma-glutamyl
      derivatives of folate, methotrexate (MTX), and para-aminobenzoic acid substrates
      and a marked preference for long-chain polyglutamates (Km values for glu4 versus
      glu1 derivatives were 17- and 15-fold lower for folate and MTX versions,
      respectively). Using an in vitro assay screen, several glutamine antagonists
      [i.e., 6-diazo-5-oxo-norleucine (DON), acivicin, and azaserine] were identified
      as human GGH inhibitors, with DON being the most potent and displaying time
      dependent inhibition. In cell culture experiments, simultaneous exposure of DON
      (10 microM) and [3H]MTX for 24 hr resulted in modest elevations of the long-chain
      gamma-glutamyl derivatives of the antifolate for HT-1080 and another human
      sarcoma line. These compounds may serve as useful lead compounds in the
      development of specific GGH inhibitors for use in examining the relationship
      between GGH activity and antifolate action and may potentially be used in
      clinical combination with antifolates that require polyglutamylation for
      effective cellular retention.

PMID- 9145922
TI  - Two tyrosine residues on the alpha subunit are crucial for benzodiazepine binding
      and allosteric modulation of gamma-aminobutyric acidA receptors.
AB  - Benzodiazepines (BZs) exert their therapeutic effects in the mammalian central
      nervous system at least in part by modulating the activation of gamma
      aminobutyric acid (GABA)-activated chloride channels. To gain further insight
      into the mechanism of action of BZs on GABA receptors, we have been investigating
      structural determinants required for the actions of the BZ diazepam (dzp) on
      recombinant alpha1 beta2 gamma2 GABA(A) receptors. Site-directed mutagenesis was
      used to introduce point mutations into the alpha1 and gamma2 GABA(A) receptor
      subunits. Wild-type and mutant GABA(A) receptors were then expressed in Xenopus
      laevis oocytes or human embryonic kidney 293 (HEK 293) cells and studied using
      two-electrode voltage-clamp and ligand-binding techniques. With this approach, we
      identified two tyrosine residues on the alpha1 subunit (Tyr159 and Tyr209) that
      when mutated to serine, dramatically impaired modulation by dzp. The Y209S
      substitution resulted in a >7-fold increase in the EC50 for dzp, and the Y159S
      substitution nearly abolished dzp-mediated potentiation. Both of these mutations
      abolished binding of the high affinity BZ receptor antagonist [3H]Ro 15-1788 to
      GABA(A) receptors expressed in HEK 293 cells. These tyrosine residues correspond
      to two tyrosines of the beta2 subunit (Tyr157 and Tyr205) previously postulated
      to form part of the GABA-binding site. Mutation of the corresponding tyrosine
      residues on the gamma2 subunit produced only a slight increase in the EC50 for
      dzp (approximately 2-fold) with no significant effect on the binding affinity of
      [3H]Ro 15-1788. These data suggest that Tyr159 and Tyr209 of the alpha1 subunit
      may be components of the BZ-binding site on alpha1 beta2 gamma2 GABA(A)
      receptors.

PMID- 9145923
TI  - Chelation and mobilization of cellular iron by different classes of chelators.
AB  - Iron chelators belonging to three distinct chemical families were assessed in
      terms of their physicochemical properties and the kinetics of iron chelation in
      solution and in two biological systems. Several hydroxypyridinones, reversed
      siderophores, and desferrioxamine derivatives were selected to cover agents with
      different iron-binding stoichiometry and geometry and a wide range of
      lipophilicity, as determined by the octanol-water partition coefficients. The
      selection also included highly lipophilic chelators with potentially cell
      cleavable ester groups that can serve as precursors of hydrophilic and membrane
      impermeant chelators. Iron binding was determined by the chelator capacity for
      restoring the fluorescence of iron-quenched calcein (CA), a dynamic fluorescent
      metallosensor. The iron-scavenging properties of the chelators were assessed
      under three different conditions: (a) in solution, by mixing iron salts with free
      CA; (b) in resealed red cell ghosts, by encapsulation of CA followed by loading
      with iron; and (c) in human erythroleukemia K562 cells, by loading with the
      permeant CA-acetomethoxy ester, in situ formation of free CA, and binding of
      cytosolic labile iron. The time-dependent recovery of fluorescence in the
      presence of a given chelator provided a continuous measure for the capacity of
      the chelator to access the iron/CA-containing compartment. The resulting rate
      constants of fluorescence recovery indicated that chelation in solution was
      comparable for the members of each family of chelators, whereas chelation in
      either biological system was largely dictated by the lipophilicity of the free
      chelator. For example, desferrioxamine was among the fastest and most efficient
      iron scavengers in solution but was essentially ineffective in either biological
      system when used at < or = 200 microM over a 2-hr period at 37 degrees. On the
      other hand, the highly lipophilic and potentially cell-cleavable
      hydroxypyridinones and reversed siderophores were highly efficient in all
      biological systems tested. It is implied that in K562 cells, hydrolysis of these
      chelators is relatively slower than their ingress and binding of intracellular
      iron. The chelator-mediated translocation of iron from cells to medium was
      assessed in 55Fe-transferrin-loaded K562 cells. The speed of iron mobilization by
      members of the three families of chelators correlated with the lipophilicity of
      the free ligand or the iron-complexed chelator. The acquired information is of
      relevance for the design of chelators with improved biological performance.

PMID- 9145924
TI  - Role of G proteins in alpha1-adrenergic inhibition of the beta-adrenergically
      activated chloride current in cardiac myocytes.
AB  - alpha1-Adrenergic receptor stimulation can inhibit the Cl- current activated by
      beta-adrenergic receptor agonists in guinea-pig ventricular myocytes. We
      investigated the role of G proteins in mediating this type of alpha-adrenergic
      response. The combined alpha- and beta-adrenergic agonist norepinephrine (NE)
      activated the Cl- current with an EC50 value of 53 nM. Preincubation of myocytes
      with PTX decreased the EC50 value for NE activation of the Cl- current to 5.9 nM,
      and addition of the alpha1-adrenergic receptor antagonist prazosin did not cause
      any further change in sensitivity to NE. These results suggest that the alpha1
      adrenergic inhibition of beta-adrenergic responses is mediated through a PTX
      sensitive G protein. However, PTX pretreatment also increased the sensitivity of
      the Cl- current to the selective beta-adrenergic agonist isoproterenol (Iso),
      which indicates that the PTX treatment increases the sensitivity to beta
      adrenergic stimulation alone and that this could account for the PTX-induced
      change in sensitivity to NE. Consistent with this idea, the selective alpha1
      adrenergic receptor agonist methoxamine was still able to inhibit the Cl- current
      activated by Iso in PTX-treated myocytes. However, the sensitivity to methoxamine
      was significantly decreased. In control cells, the Cl- current activated by 30 nM
      Iso was inhibited by methoxamine with an EC50 value of 8.3 microM, but in PTX
      treated cells, the EC50 value was 284 microM. The EC50 for methoxamine inhibition
      was similarly increased when the Cl- current was activated by 300 nM Iso. These
      data suggest that the effects of PTX on alpha1-adrenergic responses can actually
      be explained by changes in the sensitivity to beta-adrenergic stimulation. To
      verify the role for a G protein in mediating the inhibitory alpha1-adrenergic
      response, we examined the effect of methoxamine on the Cl- current activated in
      cells dialyzed with the nonhydrolyzable GTP analogue guanosine-5'-O-(3
      thio)triphosphate. Pre-exposure to methoxamine resulted in an attenuated response
      upon subsequent exposure to Iso alone. We conclude that alpha1-adrenergic
      inhibition of beta-adrenergic responses is mediated by a G protein-dependent
      mechanism that appears to be PTX-insensitive.

PMID- 9145925
TI  - N1-dansyl-spermine and N1-(n-octanesulfonyl)-spermine, novel glutamate receptor
      antagonists: block and permeation of N-methyl-D-aspartate receptors.
AB  - The effects of several N-sulfonyl-polyamines, including N1-dansyl-spermine (N1
      DnsSpm) and N1-(n-octanesulfonyl)-spermine (N1-OsSpm), were studied at
      recombinant N-methyl-D-aspartate (NMDA) receptors expressed in Xenopus laevis
      oocytes. N1-DnsSpm and N1-OsSpm inhibited NMDA receptors and were approximately
      1000-fold more potent than spermine in oocytes voltage-clamped at -70 mV. Block
      by N1-DnsSpm and N1-OsSpm was strongly voltage dependent, being more pronounced
      at hyperpolarized membrane potentials. With the Woodhull model of voltage
      dependent channel block, the values of Kd(0) were 779 microM, 882 microM, and 7.4
      mM and those of z delta were 2.58, 2.57, and 1.07 for N1-DnsSpm, N1-OsSpm, and
      spermine, respectively. This suggests that an increase in the voltage dependence
      of block together with an increase in affinity contributes to the increased
      potencies of N1-DnsSpm and N1-OsSpm compared with spermine. Sensitivity to N1
      DnsSpm was reduced by mutation NR1(N616Q) and was increased by mutations
      NR1(N616G) and NR2A(N615G). The NR1(N616G) and NR2A(N615G) mutations decreased
      the Kd(0) value of N1-DnsSpm without affecting z delta, whereas the NR1(N616Q)
      mutation reduced z delta. These mutations may alter the accessibility of part of
      the polyamine binding site within the channel pore or directly alter the
      properties of that site. Block by N1-DnsSpm (0.3 microM) was almost complete at 
      100 mV, and there was no relief of block at extreme negative membrane potentials
      (-100 to -200 mV) at wild-type NR1/NR2A channels. In contrast, block by N1-DnsSpm
      was partially relieved at extreme negative potentials at receptors containing
      NR1(N616G) or NR2A(N615G), suggesting that N1-DnsSpm can permeate these mutant
      channels but not wild-type NR1/NR2A channels. This is hypothesized to be due to
      an increase in the pore size of channels containing NR1(N616G) or NR2A(N615G),
      which allows passage of the bulky head group of N1-DnsSpm. In contrast to N1
      DnsSpm, N1-OsSpm could easily permeate wild-type NR1/NR2A channels, presumably
      because the head group of N1-OsSpm can pass through the narrowest part of the
      channel pore. N-Sulfonyl-polyamines such as N1-DnsSpm and N1-OsSpm represent a
      new class of polyamine antagonists with which to study glutamate receptor ion
      channels.

PMID- 9145926
TI  - Inhibition of recombinant Ca2+ channels by benzothiazepines and
      phenylalkylamines: class-specific pharmacology and underlying molecular
      determinants.
AB  - To understand the molecular basis of state-dependent pharmacological blockade of
      voltage-gated Ca2+ channels, we systematically characterized phenylalkylamine and
      benzothiazepine inhibition of three molecular classes of Ca2+ channels (alpha1C,
      alpha1A, and alpha1E) expressed from cDNA clones transfected into HEK 293 cells.
      State-dependent blockade figures importantly in the therapeutically desirable
      property of use-dependent drug action. Verapamil (a phenylalkylamine) and
      diltiazem (a benzothiazepine) were imperfectly selective, so differences in the
      state dependence of inhibition could be compared among the various channels. We
      found only quantitative differences in pharmacological profile of verapamil: half
      maximal inhibitory concentrations spanned a 2-fold range (70 microM for alpha1A,
      100 microM for alpha1E, and 110 microM for alpha1C), and inhibition was state
      dependent in all channels. In contrast, diltiazem produced only state-dependent
      block of alpha1C channels; alpha1A and alpha1E channels demonstrated state
      independent block despite similar half-maximal inhibitory concentrations (60
      microM for alpha1C, 220 microM for alpha1E, and 270 microM for alpha1A). To
      explore the molecular basis for the sharp distinction in state-dependent
      inhibition by diltiazem, we constructed chimeric channels from alpha1C and
      alpha1A and localized the structural determinants for state dependence to repeats
      III and IV of alpha1C, which have been found to contain the structures required
      for benzothiazepine binding. We then constructed a mutant alpha1C construct by
      changing three amino acids in IVS6 (Y14901, A1494S, 11497M) that have been
      implicated as key coordinating sites for avid benzothiazepine binding. Although
      these mutations increased the half-maximal inhibitory concentration of diltiazem
      inhibition by approximately 10-fold, the state-dependent nature of inhibition was
      spared. This result points to the existence of physically distinct elements
      controlling drug binding and access to the binding site, thereby favoring a
      "guarded-receptor" rather than a "modulated-receptor" mechanism of drug
      inhibition.

PMID- 9145927
TI  - 3-Morpholino-sydnonimine-induced suppression of human neutrophil degranulation is
      not mediated by cyclic GMP, nitric oxide or peroxynitrite: inhibition of the
      increase in intracellular free calcium concentration by N-morpholino
      iminoacetonitrile, a metabolite of 3-morpholino-sydnonimine.
AB  - This study was designed to clarify the mechanism of the inhibitory action of a
      nitric oxide (NO) donor 3-morpholino-sydnonimine (SIN-1) on human neutrophil
      degranulation. SIN-1 (100-1000 microM) inhibited degranulation (beta
      glucuronidase release) in a concentration-dependent manner and concomitantly
      increased the levels of cGMP in human neutrophils in suspension. However, further
      studies suggested that neither NO nor increase in cGMP levels were mediating the
      inhibitory effect of SIN-1 on human neutrophil degranulation because 1) red blood
      cells or 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl added
      as NO scavengers did not inhibit the effect; 2) inhibitors of cGMP synthesis
      (methylene blue) or phosphodiesterases (3-isobutyl-1-methylxanthine) did not
      produce changes in cell function correlating with the changes in cGMP. SIN-1
      releases both nitric oxide and superoxide, which together form peroxynitrite.
      Chemically synthesized peroxynitrite (1-100 microM) did not inhibit, but at high
      concentrations (1000-2350 microM), it potentiated FMLP-induced beta-glucuronidase
      release from neutrophils. Thus formation of peroxynitrite from SIN-1 does not
      explain its inhibitory effects on neutrophil degranulation. The NO-deficient
      metabolite of SIN-1, SIN-1C (330-1000 microM) inhibited human neutrophil
      degranulation in a concentration-dependent manner similar to that of SIN-1 and
      reduced the increase in intracellular free calcium induced by N-formyl-L
      methionyl-L-leucyl-L-phenylalanine. C88-3934 (330-1000 microM), another NO
      deficient sydnonimine metabolite, also inhibited human neutrophil degranulation.
      In conclusion, the data shows that the NO-donor SIN-1 inhibits human neutrophil
      degranulation in a cGMP-, NO-, and peroxynitrite-independent manner, probably
      because of the formation of more stable active metabolites such as SIN-1C. The
      results demonstrate that studies on the role of NO and/or peroxynitrite carried
      out with SIN-1 and other NO-donors should be carefully re-evaluated as to whether
      the effects found are really attributable to NO or peroxynitrite and that in
      future studies, it will be crucial to carry out control experiments with the NO
      deficient metabolites in any studies with sydnonimine NO-donors.

PMID- 9145928
TI  - Study of the interaction between aryloxypropanolamines and Asn386 in helix VII of
      the human 5-hydroxytryptamine1A receptor.
AB  - We studied the stereoselective interaction between aryloxypropanolamines and the
      human 5-hydroxytryptamine1A (5-HT1A) receptor. R- and S-enantiomers of
      propranolol, penbutolol, and alprenolol were investigated for their ability to
      bind to human 5-HT1A wild-type and Asn386Val mutant receptors. Asn386 seemed to
      act as a chiral discriminator. Although both aryloxypropanol enantiomers
      displayed lower affinity for the mutant receptors, the affinities for the S
      enantiomers were more affected. Receptor affinities of other structurally
      unrelated 5-HT1A ligands were not decreased by the mutation of Asn386 to valine.
      In addition, a series of analogues of propranolol with structural variation in
      the oxypropanolamine moiety was synthesized, and affinities for wild-type and
      Asn386Val mutant 5-HT1A receptors were determined. Both the hydroxyl and the
      ether oxygen atoms of the oxypropanol moiety seem to be required for binding at
      wild-type 5-HT1A receptors. The hydroxyl group of propranolol probably directly
      interacts with Asn386. The ether oxygen atom may be important for steric reasons
      but can also be involved in a direct interaction with Asn386. These findings are
      in agreement with the interactions of aryloxypropanolamines with Asn386 in rat 5
      HT1A receptors that we previously proposed. The loss of affinity for propranolol
      by the Asn386Val mutation could be regained by replacement of the hydroxyl group
      of the ligand by a methoxy group. This modification of the propranolol structure
      has no effect on the affinity of both enantiomers for the wild-type 5-HT1A
      receptor, which provides an alternative hypothesis for the interaction of Asn386
      with the oxypropanol oxygen atoms. According to this novel hypothesis, the
      oxypropanol oxygen atoms may both act as hydrogen bond acceptors from the NH2
      group of Asn386.

PMID- 9145929
TI  - Daily wheel running activity modifies the period of free-running rhythm in rats
      via intergeniculate leaflet.
AB  - The period of free-running rhythms (tau) in rats, as measured using a running
      wheel, is different from that measured using an Automex. The aim of this work was
      to examine the effects of lesions of the intergeniculate leaflet (IGL) on the tau
      of these two activity rhythms. When blind rats were transferred from a cage with
      a running wheel to a cage without a running wheel, the tau lengthened. The tau of
      the wheel-running activity was associated with the number of wheel revolutions
      per day. A complete lesion of the IGL lengthened the tau of the wheel-running
      activity, and caused a reduction in the number of wheel revolutions per day in
      all rats. In rats housed in cages without a running wheel, locomotor activity was
      reduced by IGL lesions, although the tau was unaffected. When IGL-lesioned rats
      were transferred from a cage with a running wheel to a cage without a running
      wheel, no further change was observed. These results indicate that the tau is
      modified by the daily activity of wheel-running, but not by general locomotor
      activity, and that the IGL may be involved in this modification.

PMID- 9145930
TI  - Sympathetic mediation of stress and aggressive competition: plasma catecholamines
      in free-living male tree lizards.
AB  - The sympathetic nervous system and adrenal catecholaminergic tissue act to
      prepare an animal for "fight or flight" by release of catecholamines into
      synapses and plasma. However, few studies have measured plasma catecholamines in
      nonmammalian vertebrates and none have measured them in free-living animals. We
      report plasma levels of norepinephrine (NE), epinephrine (EPI) and dopamine (DA)
      in free-living tree lizards (Urosaurus ornatus) bled in the field: 1) immediately
      after capture, 2) after 10 minutes of restraint, 3) immediately after a staged
      territorial encounter and 4) four minutes after the end of a staged territorial
      encounter. Time to capture and time to bleed after capture were also recorded for
      each sample. Time to capture had little effect on plasma catecholamines
      suggesting that plasma catecholamines do not rise during the brief pursuit by the
      investigator necessary to capture the lizards in the field. In contrast, plasma
      NE and EPI increased during blood collection. However, this response was very
      consistent allowing comparisons to be made using analysis of covariance to
      control for time to bleed. Results indicate that restraint stress caused a large
      increase in plasma levels of NE, E and DA. Plasma levels of NE and E, but not
      plasma DA, were also significantly elevated both immediately and 4 minutes after
      aggressive encounters, although less so than following restraint stress. These
      studies show that stress and aggression activate the sympatho-adrenal system.
      This activation could be involved in behavioral changes during aggression,
      meeting metabolic demands of the encounter, or both.

PMID- 9145931
TI  - Active immunization of rats against insulin beta subunits: effects on sleep and
      feeding.
AB  - The effects of active immunization against peripheral insulin beta subunits on
      different sleep variables and food consumption were studied in rats. Insulin
      subunits beta coupled to thyroglobulin was used as immunogen and rats immunized
      with thyroglobulin alone served as controls. Active immunization against insulin
      beta subunits affects sleep variables, particularly slow-wave sleep during the
      dark period, increasing significantly this stage of sleep and decreasing waking.
      Feeding behavior and body weight remained unchanged. These results are compatible
      with previous studies showing a positive correlation between decrease of insulin
      secretion and sleep disturbances. A possible relationship between peripheral
      alpha and or beta subunits of insulin, sleep, and feeding is suggested.

PMID- 9145932
TI  - Mice selected for low and high blood magnesium levels: a new model for stress
      studies.
AB  - Extra- and intracellular magnesium levels have previously been shown to be
      genetically controlled in humans and in the mouse. To further study this genetic
      regulation, mice were selected from a heterogeneous population, for low (MGL
      mice) and high (MGH mice) red blood cell (RBC) magnesium values. These values
      diverged rapidly in the two strains, to reach a stable difference between the
      14th and 18th generations. MGL mice also exhibited significantly lower plasma,
      kidney, and skull bone magnesium contents and higher urinary magnesium excretion
      and total brain weights. Moreover, in stressful conditions, MGL mice displayed a
      more aggressive behavior that the control MGH strain. Altogether, MGL mice showed
      a more restless behavior, a higher rectal temperature, and much higher brain
      (+17%) and urine (+200%) noradrenaline levels than the MGH animals. These
      strains, thus, constitute a new animal model for the study of magnesium
      metabolism and its relationships with catecholamines, stress sensitivity, and
      aggressive behavior.

PMID- 9145933
TI  - Selected temperature correlates with intensity of fever in rats.
AB  - Fever is considered due to an elevation of the setpoint of body temperature. The
      temperature is regulated at a higher level and the higher temperature is
      established by activation of the heat-seeking thermoeffectors. However, it is
      surprising that, for this widely accepted hypothesis, there is little
      experimental evidence of the setpoint shifting to a higher level. The present
      study shows, for the first time, a significant correlation between the magnitude
      of the temperature rise in fever and the ambient temperature selected by rats in
      a thermal gradient.

PMID- 9145934
TI  - Relationship between circadian period and size of phase shifts in Syrian
      hamsters.
AB  - In response to a light pulse, hamsters normally generate phase advances that are
      positively correlated with the length of their circadian period (tau). To
      determine whether this is a general property of the phase-shifting oscillator,
      the present study looked for a correlation between tau and phase-advance size not
      only for photic but also for nonphotic shifts. Syrian hamsters, Mesocricetus
      auratus, were entrained to light-dark cycles with a periodicity of either 23.67 h
      (the short-T group) or 24.33 h (the long-T group); after release into constant
      darkness, the short-T and long-T groups exhibited short and long taus,
      respectively. These animals were then induced to run in a novel exercise wheel
      for 3 h, starting at circadian time (CT) 7, or were exposed to 20 min of light,
      starting at CT 19. The size of the ensuing phase advances did not differ between
      the short-T and long-T groups not only for the nonphotic stimulus but also for
      the photic one, an unexpected result for the photic stimulus. Within the short-T
      groups for photic and nonphotic stimuli, the shorter tau was, the larger the
      phase advances were, another unexpected relationship. Another experiment where
      phase delays were induced by light pulses at CT 15 also failed to yield
      significant differences between the short-T and long-T groups. Independently of
      their after-effects on tau, T cycles may influence the capacity of the pacemaker
      to phase shift in ways that are still unclear but at least similar for both
      photic and nonphotic shifts.

PMID- 9145935
TI  - Mouth-state dependent changes in the judged pleasantness of water at different
      temperatures.
AB  - Dehydration increases the pleasantness of cold (0 degrees C) water (Boulze et
      al., 1983, Physiol. Behav. 30:97-102, 1983). The hypothesis that the mouth
      dryness induced by dehydration mediates this hedonic shift was investigated.
      Hydrated assessors (n = 16) judged 3 degrees C water as more pleasant after
      artificial mouth drying than did controls (n = 16). Mouth drying failed to
      influence similar judgements of water 13 degrees C, 23 degrees C, and 33 degrees
      C. We propose that preference shifts depend on temperature because cold water
      offers more rewarding relief from the sensations resulting from mouth dryness.
      Measures on saliva production were consistent with this proposal. Assessors
      swilled with water (3 degrees C, 13 degrees C, 23 degrees C, and 33 degrees C)
      for 5 s and then emptied their mouths. Measures of subsequent saliva flow
      confirmed that cold (3 degrees C) water induces an elevated rate of saliva flow
      and consequently leaves the mouth in a wetter state.

PMID- 9145936
TI  - Effects of a 2-day abstinence from smoking on dietary, cognitive, subjective, and
      physiologic parameters among younger and older female smokers.
AB  - In a field study, dietary intakes, subjective ratings of well-being, cognitive
      performance, blood pressure, and heart rate were assessed during 6 days of ad
      libitum smoking and 2 days without smoking by using an electronic diary. The
      subjects were 59 younger and older female smokers, aged 25-35 and 55-65 years,
      respectively. Smoking abstinence significantly lowered heart rate, blood
      pressure, and saliva cotinine levels, indicating a good compliance by the
      subjects. Smoking abstinence was also followed by subjectively reported decreased
      levels of relaxation and activity and by higher levels of sleepiness, negative
      strain, and craving for smoking. Mental performance as assessed with the Stroop
      task was not affected by smoking abstinence. Whereas the percentage distribution
      of the macronutrients did not change with smoking abstinence, the intake of total
      energy increased significantly by 182 kcal/day. Main effects of age were found on
      some of the dietary parameters and Stroop performance variables only. A post hoc
      analysis revealed a significant influence of the employment status factor on the
      excess caloric intake and the increased frequency of sweet consumption when under
      abstinence. These increases were significantly greater in nonemployed
      (housewives, jobless) than in working women. Further correlational analysis
      revealed strong relations between caloric intake and simultaneous craving for
      smoking and food during abstinence but not during nonabstinence days, whereas no
      relation between caloric intakes and saliva cotinine or respiratory carbon
      monoxide were obtained. These findings suggest that the availability of food
      products and subjective withdrawal symptoms are probably more important
      moderators of increased dietary intake following smoking cessation than any
      pharmacologic systemic effects of nicotine.

PMID- 9145937
TI  - Influences of fat and carbohydrate on postprandial sleepiness, mood, and
      hormones.
AB  - Paired studies were conducted in 18 healthy volunteers (9 men, 9 women) to
      investigate whether differences in mood and daytime sleepiness induced by high
      fat-low-carbohydrate (CHO) and low-fat-high-CHO morning meals were associated
      with specific hormonal responses. Plasma insulin concentrations were
      significantly higher after low-fat-high-CHO meals, and cholecystokinin (CCK)
      concentrations were significantly higher after high-fat-low-CHO meals. Subjects
      tended to feel more sleepy and less awake 2-3 h after the high-fat-low-CHO meal,
      and ratings of fatigue were significantly greater 3 h after the high-fat-low-CHO
      meal than after the low-fat-high-CHO meal. The results of the present study are
      consistent with the hypothesis that there is an association between the lassitude
      experienced after a meal and the release of CCK.

PMID- 9145938
TI  - Lesions of the ventromedial hypothalamus reduce postingestional thermogenesis.
AB  - The aim of this experiment was to evaluate the effects of ventromedial
      hypothalamus lesions on the thermogenic changes that follow food intake. Four
      groups of six Sprague-Dawley male rats were used. Under anesthesia with
      pentobarbital, the animals in the first and second groups received lesions at the
      ventromedial hypothalamus, and animals in the third and fourth groups received
      sham lesions. Body weight and food intake were monitored daily until the
      experimental procedure began. Twenty days after lesion, oxygen consumption,
      firing rate of sympathetic nerves to interscapular brown adipose tissue (IBAT),
      and IBAT temperature were monitored for 45 min both before and after 5 g food
      intake in 24 h fasted rats from the first and third groups. The same variables
      were measured in the animals of the second and fourth groups 50 days after
      receiving the lesions. Lesion placements were histologically verified. The
      results showed that lesions produced hyperphagia and obesity. Firing rate of
      nerves to IBAT, IBAT temperature, and oxygen consumption increased after food
      intake in sham-lesioned rats. This increase was significantly reduced by the
      lesion at both the 20- and 50-day time points. These findings indicate that the
      ventromedial hypothalamus controls postingestional activation of sympathetic
      discharge to IBAT. The reduction of postingestional thermogenesis could be
      involved in the development of obesity induced by lesion of the ventromedial
      hypothalamus.

PMID- 9145939
TI  - Behavioral, cardiac and cortisol responses to brief peer separation and reunion
      in cattle.
AB  - Behavioral, cardiac, and adrenal responses of heifers to short-term isolation and
      to subsequent reunion with familiar or nonfamiliar conspecifics were measured.
      Two groups of heifers were studied according to their different social
      reactivity: Aubrac heifers (n = 12) reared under suckler conditions and Friesian
      heifers (n = 12) reared under dairy management. Because these two groups could
      also react differently to human beings, testing social isolation was realized by
      removing pen mates without handling the subject. Moreover, heifers were tested in
      confinement to avoid an alteration of the cardiac response to isolation by an
      excessive motor activity. Although physical restraint can influence the
      reactions, this effect is assumed to be weak because heifers had been exposed to
      the experimental procedures, including confinement for 3 days before isolation
      test, in addition to brief periods of physical restraint occurring regularly
      according to rearing practices. Results show that social separation induced
      struggling and large increases in vocalization, heart rate, and plasma cortisol
      concentrations in all heifers. Except for vocalization, these effects were more
      severe in Aubrac than in Friesian heifers. For all heifers, isolation-induced
      distress was positively correlated with the duration of social contacts they
      engaged with the pen mates prior to separation. Behavioral responses, i.e.,
      struggling and vocalization, decreased when conspecifics were brought back,
      independently of their familiarity to the subject. In contrast, the heart rate
      decline induced by the entrance of conspecifics was more pronounced in response
      to reintroduction of pen mates. These findings indicate that social isolation is
      a severe psychological stress in cattle and that the mere sight of conspecifics
      reduces behavioral distress regardless of peer identity. The isolation-induced
      distress depends on the genetic and rearing backgrounds of the heifers without
      allowing to differentiate their respective effects.

PMID- 9145940
TI  - Time course of the effects of a high-fat diet and voluntary exercise on muscle
      enzyme activity in Long-Evans rats.
AB  - This study examined the time course of the effects of a high-fat diet and
      voluntary running exercise on rat skeletal muscle carnitine acyltransferase
      (CAT), beta-hydroxy-acyl-CoA dehydrogenase (HAD), and citrate synthase (CS)
      activities. Sixty male Long-Evans rats were randomly allocated to receive either
      a standard (12% fat by energy) laboratory chow diet (CHOW) or a high-fat (76% by
      energy) diet (HFD) and placed in running wheels for up to 6 weeks. Energy intakes
      and weekly voluntary running distances were similar in the CHOW and HFD rats. In
      both groups, weekly training distance more than doubled from week 4 to week 6.
      However, increased training had little influence on soleus (s) CAT(s), HAD(s),
      and CS(s) activities. CAT(s) and HAD(s) activities were higher in the HFD rats
      than in the CHOW rats from 2 weeks onward (p < 0.005), and CS(s) activities were
      not different between groups and remained constant over time. In contrast,
      increased training distance after 4 weeks in the CHOW rats resulted in an
      increase in deep vastus (v) CAT(v) activities to values similar to those in HFD
      rats prior to increases in training volume (p < 0.005) but had no effect on their
      HAD(v) and CS(v) activities. Increases in HAD(v) and CS(v) activities with
      increased training volume were only seen in the HFD rats (p < 0.005). HAD(v)
      activities and HAD/CS(v) activity ratios correlated with training distance in the
      HFD rats only (p < 0.001 and p < 0.01, respectively). These results suggest that
      a high-fat diet improves the beta-oxidation capacity of rat predominantly slow
      twitch soleus muscle and enhances the effects of modest levels of training on the
      mitochondrial density and beta-oxidation capacity of rat deep vastus mixed fast-
      and slow-twitch muscles.

PMID- 9145941
TI  - Effects of systemic interleukin-1beta administration on daily drinking and renal
      excretory function in conscious rats.
AB  - To elucidate the roles of interleukin-1beta (IL-1beta), a cytokine with several
      diverse actions, in the control of body fluid balance, its effects on daily
      drinking behavior and renal excretory function were examined in conscious rats.
      Administration of IL-1beta (4 microg/kg, I.P.) resulted in the suppression of
      both daily drinking and food intake and a decrease in daily urinary sodium and
      potassium excretion, but had no effect on urine volume. The IL-1beta-induced
      decrease in sodium excretion was abolished in renal-denervated rats. Kainic acid
      was then injected into the anteroventral third ventricle region, including the
      organum vasculosum of the lamina terminalis, to examine whether neurons in this
      region are involved in the IL-1beta-induced responses; the effects on daily
      drinking and urinary sodium and potassium excretion were abolished, whereas the
      effects on food intake, although attenuated, were still present. In contrast,
      electrical lesion of the subfomical organ did not affect the IL-1beta-induced
      responses. Thus, IL-1beta seems exert its effects on body fluid balance at
      several distinct sites in the central nervous system.

PMID- 9145942
TI  - Tail pinch induces fos immunoreactivity within several regions of the male rat
      brain: effects of age.
AB  - Brief, intermittent stressors, such as low-level foot shock or tail pinch, induce
      a general excitement and autonomic arousal in rats that increases their
      sensitivity to external incentives. Such stimulation can facilitate a variety of
      behaviors, including feeding, aggression, sexual activity, parental behavior, and
      drug taking if the appropriate stimuli exist in the environment. However, the
      ability of tail pinch to induce general arousal and incentive motivation appears
      to diminish with age. Here we report on the ability of tail pinch to induce Fos
      immunoreactivity within several brain regions as a function of age. Young (2-3
      months) and middle-aged (12-13 months) male rats were administered either five
      tail pinches (one every 2 min), one tail pinch, or zero (sham) tail pinches (n =
      4 per stimulation condition). Rats were sacrificed 75 min following the onset of
      stimulation, and their brains were prepared for immunocytochemical detection of
      Fos protein. Fos immunoreactivity was induced by one and five tail pinches in
      several brain regions, including the anterior medial preoptic area (mPOA),
      paraventricular nucleus of the hypothalamus (PVN), paraventricular nucleus of the
      thalamus (PV-Thal), medial amygdala (MEA), basolateral amygdala (BLA), lateral
      habenula (LHab), and ventral tegmental area (VTA), of young rats compared with
      those that received zero tail pinches. In contrast to young rats, middle-aged
      rats had significantly less Fos induced by one and five tail pinches in the mPOA,
      PVN, MEA, BLA, and VTA, but an equivalent amount induced in the LHab. Fos
      immunoreactivity was not found within the medial prefrontal cortex, nucleus
      accumbens, striatum, lateral septum, or locus coeruleus in either young or old
      rats. Tail pinch appears to activate regions of the brain known to be involved in
      behavioral responses to both incentive cues and stressors. The lower level of
      cellular reactivity to tail pinch in middle-aged rats suggests a diminished
      neural responsiveness to incentives and stressors.

PMID- 9145943
TI  - A comparison of resting metabolic rate, self-rated food intake, growth hormone,
      and insulin levels in obese and nonobese preadolescents.
AB  - The objective was to investigate metabolic (resting metabolic rate), behavioral
      (energy intake), and endocrine variables (fasting insulin and growth hormone
      levels) potentially responsible for a positive energy balance in obese children
      in a cross-sectional study. The study was in 25 obese children aged 8 to 12 years
      and 21 nonobese children of the same age range. Weight, height, lean body mass
      (LBM) and fatmass (FM) were measured by bioelectrical impedance analysis, resting
      metabolic rate (indirect calorimetry) for the duration of 25 min, 7-day food
      records and fasting levels of insulin and human growth hormone (HGH). In the
      total sample, no differences were found in resting metabolic rate (RMR controlled
      for differences in weight) and energy intake between groups, whereas fasting
      insulin level was significantly higher and basal growth hormone concentration was
      significantly lower in the obese children. In RMR, there were significant age
      dependent differences only in 10-year-old children, with the obese subjects
      showing lower values. The results fit in a multidimensional model, taking into
      account a critical period in prepubertal age for the development of childhood
      obesity. This period may be characterized by a reduced RMR, which results in an
      increased body weight, even if there is no excessive energy intake.

PMID- 9145944
TI  - Single and repeated environmental stress: effect on plasma oxytocin,
      corticosterone, catecholamines, and behavior.
AB  - Rat studies were done to further characterize an environmental model of stress
      designated shaker stress (SS). Plasma oxytocin (OT), corticosterone (CS),
      norepinephrine (NE), and epinephrine (E) were measured before and after 5 or 30
      min of SS applied one time or applied 10 times over a 2-week period. The major
      findings were partial adaptation of plasma E within 30 min of acute SS,
      adaptation of plasma CS baselines but not responses to chronic SS, and complete
      adaptation of plasma OT responses to chronic SS. Poststress behavior during
      chronic SS was affected in the following ways: freezing time habituated,
      defecation and rearings increased, and grooming and teeth chattering remained
      relatively constant. The results show that SS produces consistent patterns of
      hormonal and behavioral responses; some aspects of the patterns are similar to
      those elicited by other environmental stresses, whereas some aspects are unique
      to SS. We conclude that rats do not adapt to repeated SS but rather that most
      hormonal and behavioral defense mechanisms are renewable on a daily basis.

PMID- 9145945
TI  - The development of anticipatory nausea in patients receiving adjuvant
      chemotherapy for breast cancer.
AB  - Previous research on anticipatory nausea in cancer patients has focused on its
      occurrence in the clinic before chemotherapy infusions. The present study is the
      first, to our knowledge, to examine the development of anticipatory nausea across
      eight chemotherapy infusions for three time periods (night before, morning of,
      and immediately prior to each infusion). Based on classical conditioning
      experiments conducted with animal subjects, we hypothesized that the severity of
      anticipatory nausea would increase as the time for scheduled infusions
      approached. Eighty-two women diagnosed with Stage I or II breast cancer were
      assessed for the intensity of anticipatory nausea at three time periods prior to
      eight scheduled infusions of outpatient adjuvant chemotherapy. Analyses indicated
      a significant interaction between number of infusions experienced and temporal
      proximity to the infusion, supporting the hypothesis. Changes in the severity of
      anticipatory nausea across infusions were consistent with conditioned learning
      predictions. These results contribute to a growing recognition of the importance
      of conditioning principles for understanding side effects of chemotherapy for
      cancer and may have implications for the management of side effects secondary to
      a variety of pharmacotherapies in clinical practice.

PMID- 9145946
TI  - Caloric intake and weight gain of rats depends on endogenous fat preference.
AB  - Within outbred colonies, subpopulations of rats exist that exhibit inherent
      preferences for one type of macronutrient over another (e.g., fat vs.
      carbohydrate). Prior investigations into the effect of dietary manipulations on
      consumption or weight gain have not taken into account endogenous macronutrient
      preferences. The purpose of this study was to examine whether inherent fat
      preferences translate into differences in caloric consumption and weight gain in
      rats when fed high-fat and high-carbohydrate diets. Rats that exhibited a
      preference for fat were identified using a previously described paradigm and were
      subsequently placed on either a high-fat or high-carbohydrate diet. Daily caloric
      intakes and weekly weights were monitored over a 28-day period and compared with
      data for animals with a low-fat preference on the same diets. By the conclusion
      of the study, the low-fat-preferring rats on the high-carbohydrate diet had
      consumed significantly more calories than the high-fat-preferrers maintained on
      the same diet. In contrast, the amounts of calories consumed on the high-fat diet
      were not significantly different between the low- and high-fat-preferring
      animals. Those animals with a preference for fat placed on a high-carbohydrate
      diet weighed significantly less by the end of study, even though they consumed
      the same number of calories as animals on the high-fat diet. We conclude that the
      outcome of nutritional studies designed to examine caloric intake and weight gain
      can be influenced by the innate macronutrient preference of the animal.

PMID- 9145947
TI  - Early environmental influences can attenuate the blood pressure response to acute
      stress in borderline hypertensive rats.
AB  - The objective of this experiment was to test the hypothesis that early
      environmental influences could affect cardiovascular reactivity to acute stress
      in borderline hypertensive rats. This study utilized a cross-fostering paradigm
      in which borderline hypertensive rat (BHR) pups were reared by their natural
      spontaneously hypertensive rat (SHR) mothers, by an adoptive SHR dam, or by an
      adoptive Wistar-Kyoto female. Several maternal behavior measures were taken
      throughout weaning. Cardiovascular responses to acute stress were measured in
      adult BHR offspring. SHR dams spent significantly more time engaged in arched, as
      contrasted with passive, nursing behaviors throughout the preweaning period.
      Although strain of dam had no effect on resting blood pressure or heart rate, BHR
      reared by WKY dams had a greatly reduced blood pressure response to acute stress
      compared with BHR raised by either natural or adoptive SHR dams. These results
      suggest that the expression of cardiovascular characteristics in the BHR can be
      modified by early environmental influences and support the hypothesis that the
      expression of the hypertensive phenotype in the BHR is dependent upon information
      that is conveyed both genetically and environmentally.

PMID- 9145948
TI  - Cocaine self-administration in ovariectomized rats is predicted by response to
      novelty, attenuated by 17-beta estradiol, and associated with abnormal vaginal
      cytology.
AB  - Parameters of cocaine self-administration behavior and vaginal cytological
      changes were assessed in ovariectomized rats during and after chronic self
      administration. Response to novelty as measured by locomotor activity was found
      to correlate with cocaine self-administration on both fixed ratio (FR) and
      progressive ratio (PR) schedules of reinforcement. Chronic 17-beta estradiol (E2)
      replacement did not affect cocaine self-administration on FR or PR schedules of
      reinforcement. Acute E2 administration decreased cocaine self-administration on a
      PR schedule of reinforcement on the day of and on the two days following hormone
      treatment. Finally, the proliferation of vaginal epithelia following acute E2 was
      potentiated in rats both during cocaine self-administration and 30 days into
      withdrawal when compared with non-drug-exposed animals. These results identify
      response to novelty as a behavioral index predictive of cocaine self
      administration liability in female rats and additionally provide evidence of
      psychostimulant-hormonal interactions highly relevant to female behavior and
      physiology.

PMID- 9145949
TI  - Effects of preloads of water and saline on thermal dehydration-induced thirst.
AB  - The relative contribution of cellular and extracellular water deficits to the
      genesis of thirst due to thermal dehydration was studied in male Sprague-Dawley
      rats following exposure to a 40 degrees C environment for 4 h. Intragastric
      (I.G.) and intravenous (I.V.) preloads of water reduced the elevated plasma
      sodium and plasma osmolality of thermally dehydrated rats to control levels, but
      preloads of saline did not. I.G. and I.V. preloads of saline returned the
      hematocrit and plasma protein concentration of thermally dehydrated rats to
      control levels. Both the I.G. water preload and the I.G. saline preload reduced
      water intake, with the I.G. water preload having a greater effect. The I.V. water
      preload reduced water intake nearly to control levels, whereas the I.V. saline
      preload was without effect on water intake. These data indicate that the water
      intake of thermally dehydrated rats is primarily due to a cellular water deficit
      and that oral and gastric factors are also important in terminating water intake
      in thermally dehydrated rats.

PMID- 9145950
TI  - Neuroendocrine-associated behavioral patterns in the male Asian elephant (Elephas
      maximus).
AB  - Steroid-responsive behaviors have been reported in various species; however, the
      reports thus far on the male Asian elephant (bull) during musth are few in number
      and most have been conducted on single captive animals for short time periods.
      The purpose of this investigation was to perform a longitudinal study on steroid
      responsive behavior in 3 male Asian elephants from a captive herd of 11 male
      Asian elephants in Nepal. Male Asian elephants were 18, 25, and 43 years old. The
      animals had serum collected for 11 months and were observed on a daily basis for
      aggressive behavior according to the Species Survival Plan (SSP) collection
      protocol on SSP data sheets. Testosterone (T) and dihydrotestosterone (DHT) were
      measured in each animal by radioimmunoassay. Testosterone levels rose during
      musth 26-fold compared to nonmusth, and DHT was elevated 12-fold in musth.
      Maximal aggressive behavior episodes occurred during peak elevations of T and
      DHT, with correlation coefficients of 0.82 and 0.89, respectively. Therefore, we
      suggest that the aggressive episodes are dependent on elevated circulating
      androgens acting on androgen-responsive neural tissues.

PMID- 9145951
TI  - Development of the enhanced neural response to NaCl in Fischer 344 rats.
AB  - To examine the development of strain differences in the response of the chorda
      tympani nerve (CT) to NaCl, integrated CT responses to NaCl were recorded from
      Wistar and F344 rats between 15 and 36 days old. NaCl responses before and after
      the application of amiloride were expressed relative to 0.5 M NH4Cl as a
      standard. At 15-17 days old, there were no significant strain differences in the
      magnitude of NaCl responses. Strain differences emerged at 21-23 days old with
      responses of F344 rats significantly higher than those of Wistars; these
      differences became more pronounced at 34-36 days old. Amiloride significantly
      reduced responses to NaCl at all ages and eliminated any differences between the
      strains. Changes in neural responsiveness correspond with the emergence of the
      behavioral expression of F344 salt aversion.

PMID- 9145952
TI  - Maternal behavior in rats with kainic acid-induced lesions of the hypothalamic
      paraventricular nucleus.
AB  - The rat maternal behavior consists of different pup-caring activities, such as
      retrieving, licking, and crouching. Mothers also build a nest, consume more food,
      are more aggressive, and show less fear behavior than in other stages of the
      reproductive cycle. It has been reported that oxytocin (OT) and the milk-ejection
      pathway could be involved in modulating maternal behavior. The paraventricular
      nucleus (PVN) of the hypothalamus forms part of the milk-ejection pathway and is
      also the major source of OT release in the brain. Kainic acid (KA) lesions (0.5
      microg/0.5 microl) in the PVN performed on day 2 after parturition, affected
      retrieving behavior in the mother rat and produced a decrease in pups' weight
      gain. Because KA destroys only cell bodies, the changes that we observed could be
      due to the local destruction of neurons, rather than that of the fibers of
      passage. No alteration was observed in other components of the pup-caring
      activities, food intake, aggressive behavior, and fear in the lesioned mothers.

PMID- 9145953
TI  - The effects of females' susceptibility on the coexistence of multiple pathogen
      strains of sexually transmitted diseases.
AB  - We study the dynamics of sexually transmitted pathogens in a heterosexually
      active population, where females are divided into two different groups based on
      their susceptibility to two distinct pathogenic strains. It is assumed that a
      host cannot be invaded simultaneously by both disease agents and that when
      symptoms appear--a function of the pathogen, strain, virulence, and an
      individual's degree of susceptibility--then individuals are treated and/or
      recover. Heterogeneity in susceptibility to the acquisition of infection and/or
      in variability in the length of the infection period of the female subpopulations
      is incorporated. Pathogens' coexistence is highly unlikely on homogeneously
      mixing female and male populations with no heterogeneity among individuals of
      either gender. Variability in susceptibility in the female subpopulation makes
      coexistence possible albeit under a complex set of circumstances that must
      include differences in contact/mixing rates between the groups of females and the
      male population as well as differences in the lengths of their average periods of
      infectiousness for the three groups.

PMID- 9145954
TI  - Competitive exclusion in a vector-host model for the dengue fever.
AB  - We study a system of differential equations that models the population dynamics
      of an SIR vector transmitted disease with two pathogen strains. This model arose
      from our study of the population dynamics of dengue fever. The dengue virus
      presents four serotypes each induces host immunity but only certain degree of
      cross-immunity to heterologous serotypes. Our model has been constructed to study
      both the epidemiological trends of the disease and conditions that permit
      coexistence in competing strains. Dengue is in the Americas an epidemic disease
      and our model reproduces this kind of dynamics. We consider two viral strains and
      temporary cross-immunity. Our analysis shows the existence of an unstable endemic
      state ('saddle' point) that produces a long transient behavior where both dengue
      serotypes cocirculate. Conditions for asymptotic stability of equilibria are
      discussed supported by numerical simulations. We argue that the existence of
      competitive exclusion in this system is product of the interplay between the host
      superinfection process and frequency-dependent (vector to host) contact rates.

PMID- 9145955
TI  - A theoretical approach to G-protein modulation of cellular responsiveness.
AB  - Structure and function of cells often depend critically on molecular signals
      arriving at their surface. There are universal mechanisms of signal transduction
      and signal processing across cell membranes. In this paper the mechanisms
      involving guanine-nucleotide regulatory proteins ("G-proteins") and certain
      receptor-kinases are considered. On the basis of recent findings in molecular
      biology a mathematical model is developed taking into account all essential
      components in the biochemical network between first and second messenger. There
      are two coupled feedback loops inherent in this process. The model finally
      consists of three nonlinear equations, which are obtained from a system of
      originally ten equations by using conservation laws and quasi-steady state
      conditions. The second part of the paper contains a mathematical analysis of the
      model. Solutions describing the temporal development of the involved biochemical
      species are shown to be bounded, more specifically to remain, independent of the
      size of the input signal, in a bounded domain of the state space. For the
      situation of stationary input signals existence, uniqueness and asymptotic
      stability of steady states are derived. We also demonstrate biologically relevant
      stimulus-response properties like monotonicity and saturation effects. For
      temporally non-constant input signals we show numerically that the model is able
      to produce phenomena of hypersensitivity and desensitization which are important
      characteristics of cellular responsiveness.

PMID- 9145956
TI  - Photodynamic treatment of skin malignancies with aminolevulinic acid. Emphasis on
      anatomical observations and in vitro erythema visual assessment.

PMID- 9145957
TI  - Utilizing the ultraviolet (UV detect) camera to enhance the appearance of
      photodamage and other skin conditions.
AB  - BACKGROUND: Ultraviolet (UV) light (Wood's light) has been used since 1903 to
      document alterations in the pigment of the skin. The development of standard UV
      photographic methods has allowed better opportunities for patient education and
      the monitoring of their therapeutic progress. OBJECTIVE: To incorporate
      standardized UV photography into our cosmetic dermatology practice as a tool for
      patient teaching and monitoring therapeutic programs. METHODS: Patients with
      Fitzpatrick Type I to III skin types were photographed with visible and
      ultraviolet light. The resultant photographic prints were discussed with the
      patient. When appropriate, therapeutic programs to reverse the findings were
      instituted for these patients. Follow-up photographs were used to document
      changes. RESULTS: The UV camera became a useful tool in our practice. One picture
      was worth a thousand words. The UV camera documented pigment changes, melasma,
      vitiligo, and posttraumatic or postsurgical hypopigmentation. The UV camera was
      also useful to monitor treatment programs designed to redistribute the pigment.
      CONCLUSION: The UV camera should become an integral part of sun damage detection
      both in the physician's office and in the community. Not only does the camera
      document pigmentary changes but it also demonstrates improvement after
      therapeutic intervention.

PMID- 9145959
TI  - Glycolic acid peels in the treatment of melasma among Asian women.
AB  - BACKGROUND: Melasma is a common disorder of facial hyperpigmentation among Asian
      women. Many modalities of treatment are available but none is satisfactory.
      OBJECTIVE: This study was undertaken to see if glycolic acid peels are effective
      and safe in the treatment of melasma and fine facial wrinkling. METHODS: Ten
      Asian women with moderate to severe melasma were recruited into the study. The
      women had twice daily applications of a cream containing 10% glycolic acid and 2%
      hydroquinone (Neostrata AHA Age Spot and Skin Lightening Gel) to both sides of
      the face, and glycolic acid peels every 3 weeks (20-70%) to one-half of the face
      using Neostrata Skin Rejuvenation System. All patients had to use a sunblock (SPF
      15%). At regular intervals and at the end of 26 weeks (or after eight peels) the
      degree of improvement of pigmentation and fine facial wrinkling on each side of
      the face were assessed. Any skin irritation or side effects were also noted.
      Assessment was by an independent dermatologist, the patients themselves, and the
      use of the Munsell color chart and photographs. The nonparametric Wilcoxon Rank
      Sum test was used for statistical analysis. RESULTS: The melasma and fine facial
      wrinkling improved on both sides of the face. The side that received glycolic
      acid peels did better but the results were not statistically significant (P >
      0.059). CONCLUSION: A cream containing 10% glycolic acid and 2% hydroquinone
      (Neostrata AHA Age Spot and Skin Lightening Gel) improved melasma and fine facial
      wrinkling in Asian women. In combination with glycolic acid peels at 3-week
      intervals the lightening of melasma is subjectively much better. This improvement
      does not reach statistical significance and the sample size is small (n = 10).

PMID- 9145958
TI  - Glycolic acid peels for postinflammatory hyperpigmentation in black patients. A
      comparative study.
AB  - BACKGROUND: Treatment of postinflammatory hyperpigmentation in patients of
      Fitzpatrick skin types IV, V, and VI is difficult. Glycolic acid peels are useful
      for pigment dyschromias in caucasians; however, there are no controlled studies
      examining their safety and efficacy in dark-complexioned individuals. OBJECTIVE:
      To determine if serial glycolic acid peels provide additional improvement when
      compared with a topical regimen of hydroquinone and tretinoin. METHODS: Nineteen
      patients with Fitzpatrick skin type IV, V, or VI were randomized to a control or
      peel group. The control group applied 2% hydroquinone/10% glycolic acid gel twice
      daily and 0.05% tretinoin cream at night. The peel patients used the same topical
      regimen and, in addition, received six serial glycolic acid peels (68% maximum
      concentration). Patients were evaluated with photography, colorimetry, and
      subjectively. RESULTS: Sixteen patients completed the study. Both treatment
      groups demonstrated improvement, but the patients receiving the glycolic acid
      peels showed a trend toward more rapid and greater improvement. The peel group
      also experienced increased lightening of the normal skin. CONCLUSIONS: This pilot
      study demonstrates that serial glycolic acid peels provide an additional benefit,
      with minimal adverse effects, for the treatment of postinflammatory
      hyperpigmentation in dark-complexioned individuals.

PMID- 9145960
TI  - The immunohistochemical characteristics of the basosquamous cell carcinoma.
AB  - BACKGROUND: The basosquamous cell carcinoma (BSCC) is a poorly defined and often
      misunderstood cutaneous malignancy. OBJECTIVE: The purpose of this study was to
      compare, using immunohistochemical techniques, the BSCC, basal cell carcinoma
      (BCC), and squamous cell carcinoma (SCC). METHODS: BSCC occurring at Pennsylvania
      State University over the past 10 years were identified. Choosing seven BCC, and
      nine SCC as controls, all specimens were stained for keratin, lack of apoptosis,
      glycoproteins, and altered gene products using the avidin/biotin and strep-avidin
      immunoperoxidase techniques. Each malignancy was then graded for the percentage
      of cells stained with each marker. RESULTS: Of the markers studied, all stained
      to varying degrees the malignant aspects of the specimens. There were similar
      patterns between tumors, with the BSCC showing a transition zone between typical
      BCC and SCC. This was most striking for Ber-EP4, where over two-thirds of the BCC
      stained, none of the SCC, and half of the BSCC showed reactivity. CONCLUSION:
      BSCC has staining patterns similar to both the BCC and SCC. The presence of a
      transition zone does not support the concept that all BSCC are collision tumors,
      but rather a differentiation of one tumor into another. We confirm earlier
      reports that Ber-EP4 could be used to distinguish between classic BCC and SCC.
      AE1/AE3, bcl-2, TGF-alpha, and p53 were not helpful in separating the tumors.

PMID- 9145961
TI  - Saturated phenol as a local anesthetic for manual dermabrasion.
AB  - BACKGROUND: Dermabrasion is a painful procedure that requires the use of
      anesthetics, which, in their application, adds to the patient's pain. OBJECTIVE:
      To describe the use of saturated phenol as a transient local anesthetic for
      manual dermabrasion. METHODS: Manual dermabrasion of small areas (4 cm2) was
      performed in 12 patients using saturated 88% phenol as a local anesthetic.
      RESULTS: Cosmetic results were good or excellent in 11 patients. Pain was minimal
      in eight patients, moderate in three, and absent in one. CONCLUSION: Saturated
      phenol is an effective and safe anesthetic alternative for manual dermabrasion of
      small areas.

PMID- 9145962
TI  - Long-term efficacy and safety of Jessner's solution and 35% trichloroacetic acid
      vs 5% fluorouracil in the treatment of widespread facial actinic keratoses.
AB  - BACKGROUND: Few studies have examined the long-term efficacy of fluorouracil (FU)
      or chemical peels for the treatment of actinic keratoses (AK). Our earlier work
      examined the efficacy and safety of a medium-depth chemical peel compared with
      the standard regimen of topical FU in the treatment of widespread facial AK
      through 12 months. OBJECTIVES: To determine long-term efficacy of both treatments
      by extending our observations through 32 months. METHODS: Fifteen patients with
      severe facial actinic damage were treated on the left side with a single
      application of Jessner's solution and 35% trichloroacetic acid and on the right
      side with twice daily applications of 5% FU cream for 3 weeks. Parameters
      evaluated at 1, 6, 12, and 32 months included counts of visible AK, random skin
      biopsies from both treatment areas, development of intercurrent neoplasms, and
      surveys assessing sun exposure. RESULTS: Eight patients were available for
      reevaluation at 32 months. Both treatment sides showed a reduction in mean number
      of AK at 12 months followed by an increase in mean AK number between 12 and 32
      months. Improvements in biopsies of clinically actinically damaged skin were seen
      in keratinocytic atypia, hyperkeratosis, parakeratosis, and inflammation at all
      treatment times during the study with both treatments. Three squamous cell
      carcinomas developed in the patients after initial treatment; one developed on
      the side treated with the peel, and two developed on the side treated with
      fluorouracil. Surveys failed to demonstrate an association between sun exposure
      and clinical response. CONCLUSION: Based on these findings, patient with
      widespread actinic keratoses treated with medium-depth chemical peel or with 5%
      FU should be reevaluated yearly or every 1.5 years for reappearance of AK and
      retreatment.

PMID- 9145963
TI  - Volunteer melanoma screenings. Follow-up, compliance, and outcome.
AB  - BACKGROUND: Follow-up information on free melanoma screening clinics is not
      readily available. OBJECTIVE AND METHODS: We studied the follow-up, compliance,
      and outcome of positive screenees after a screening campaign for melanoma in the
      Netherlands. RESULTS: Of the 4146 participants, 486 (11.7%) had a suspicious
      premalignant or malignant lesion warranting referral to his or her general
      physician indicating the proposed line of management. Participants with
      borderline lesions were not referred. Referral of borderline cases should have
      resulted in a considerable increase of the number of positive screenees (18.1%).
      All positive screenees but two gave permission for follow-up. Only 18 screenees
      (3.7%) were lost during follow-up. Moreover, one screenee with a presumed basal
      cell carcinoma and six screenees suspicious of having a premalignant lesion
      decided not to seek medical attention despite several reminders. The positive
      predictive value for melanoma was 17.2%, and for nonmelanoma skin cancers was
      42.9%. CONCLUSION: A selective referral policy may reduce the generated costs of
      melanoma screenings substantially. Adequate follow-up of positive screenees is
      mandatory in order to determine the ultimate yield and usefulness of such
      campaigns.

PMID- 9145964
TI  - Basal cell carcinoma involving the lacrimal canaliculus. A documented mechanism
      of tumor spread.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common malignant tumor of the
      eyelid and periocular tissues but rarely involves the lacrimal system. In
      addition, BCC in this location frequently recur due to inadequate margin control.
      A further understanding of the pathophysiology of periocular BCC was addressed.
      OBJECTIVE: To report two rare cases of BCC involving the lacrimal system and to
      account for subtle clinical features yet extensive tissue spread of periocular
      BCC. METHODS: Using the Mohs micrographic surgical technique, we describe two
      patients with a BCC involving the lacrimal system that histologically tracked
      beyond clinically apparent margins. RESULTS: Spread of BCC along mucosal surfaces
      is documented. CONCLUSION: Rare involvement of the lacrimal system by a BCC is
      reported in two patients. Superficial histologic involvement can explain the
      ability of BCC to extend locally and escape adequate treatment.

PMID- 9145965
TI  - Vulvar basal cell carcinoma.
AB  - BACKGROUND: Vulvar basal cell carcinoma is a rare neoplasm that often displays
      aggressive biologic behavior. Recurrence after simple excision is common, and
      metastases have been reported. Early diagnosis is essential and rests upon
      histopathologic examination of biopsy specimens, since the clinical appearance of
      these neoplasms may be deceptively innocent. CASE: A 65-year-old woman was seen
      with a nonhealing skin lesion on the right vulva. Physical examination revealed a
      0.3 X 0.3 cm crusted papule on the right labium majus. A saucerization biopsy was
      performed. Histopathologic examination of the biopsy specimen revealed basal cell
      carcinoma. The patient underwent Mohs micrographic excision of the tumor, the
      total extent of which measured 0.9 X 1.8 cm. CONCLUSION: Vulvar basal cell
      carcinoma is a rare but important consideration in the differential diagnosis of
      cutaneous vulvar lesions. Accurate diagnosis depends upon a high index of
      suspicion, biopsy, and histopathologic examination. Mohs micrographic excision is
      the treatment of choice.

PMID- 9145966
TI  - Ileal conduit diversion after radical cystectomy: pro.

PMID- 9145967
TI  - Reconstruction of the urinary tract after radical cystectomy: the case for
      continent urinary diversion.

PMID- 9145968
TI  - Prostate-specific antigen nadir of 0.5 ng/mL or less defines disease freedom for
      surgically staged men irradiated for prostate cancer.
AB  - OBJECTIVES: This report describes treatment results of men with prostate cancer
      staged with a pelvic lymph node dissection. Disease freedom was defined by a
      prostate-specific antigen (PSA) level nadir of 0.5 ng/mL or less. METHODS: Since
      1984, 363 men with clinical Stage T1 or T2, surgical stage node-negative prostate
      cancer were simultaneously irradiated with a retropubic iodine 125 prostate
      implant followed by external-beam radiation. The average pretreatment PSA level
      was 13.6 ng/mL (median 8.5, range 0.3 to 188). Disease freedom was defined as the
      achievement and maintenance of a nadir of 0.5 ng/mL or less. Treatment failure
      was defined as a nadir of more than 0.5 ng/mL or a PSA rise above this level. The
      median follow-up is 5 years (average 5.5, range 1 to 12.5). RESULTS: For all men,
      the 5- and 10-year disease-free survival results are 78% and 65%. Of 201 men with
      a minimum 5-year follow-up, 140 (70%) are disease free. The 5-year disease-free
      survival rate by pretreatment PSA is 4.0 ng/mL or less, 93%; 4.1 to 10.0 ng/mL,
      87%; 10.1 to 20.0 ng/mL, 72%; and greater than 20.0 ng/mL, 45%. CONCLUSIONS: The
      10-year disease-free survival results of retropubic implantation, a technique
      considered a failure by many investigators, followed by external-beam radiation
      appear to be better than either technique given separately and are comparable to
      the results following radical prostatectomy. These results are valuable because
      they form a baseline that may be improved upon in the future by simultaneous
      irradiation using the transperineal implant technique.

PMID- 9145969
TI  - Laparoscopic adrenalectomy: a new standard of care.
AB  - OBJECTIVES: Adrenalectomy is the mainstay of treatment for adrenal tumors. A
      variety of surgical approaches to the adrenal gland have been described. We
      studied the feasibility of laparoscopic adrenalectomy (LA), compared laparoscopic
      with open adrenalectomy (OA), and studied the hemodynamic changes in patients
      with pheochromocytoma. METHODS: Our early experience with 20 consecutive LAs is
      compared with a contemporaneous, matched control cohort of 20 patients who
      underwent OA via a flank or subcostal incision. LA was performed via a
      transperitoneal approach, following a standardized surgical technique. RESULTS:
      LA was successfully completed in 18 of 20 cases. Average operating time in the
      first 5 cases was 261 minutes, but, with further experience, a significant
      decrease in operative time was seen in the last cohort of 4 patients (155
      minutes) (P = 0.0018). There was no significant difference in operative time or
      degree of blood loss between LA and OA groups. Patients who underwent LA required
      lower doses of postoperative parenteral narcotics (P = 0.0169), had a shorter
      hospital stay (mean 3.2 days) (P < 0.0001), and had a shorter convalescent period
      (mean 3.1 weeks) (P < 0.0001). Complications in the laparoscopic group (chronic
      port site pain in 1 patient, intra-abdominal fluid collection in another)
      occurred in the 2 patients who required open conversion. These 2 patients had
      large adrenal tumors (9 and 7 cm in diameter, respectively). LA resulted in
      similar hemodynamic changes as OA in patients with pheochromocytoma. CONCLUSIONS:
      LA is a safe and effective approach in most patients with adrenal pathology.
      Benefits include excellent operative exposure and visualization, less
      postoperative pain, shorter hospital stay and convalescent period, and improved
      cosmetic result. Pheochromocytoma is not a contraindication to LA. Patients with
      large adrenal tumors (larger than 6 cm), evidence of venous involvement, or
      invasion into surrounding tissue should be approached cautiously.

PMID- 9145970
TI  - Antimicrobial prophylaxis prior to shock wave lithotripsy in patients with
      sterile urine before treatment: a meta-analysis and cost-effectiveness analysis.
AB  - OBJECTIVES: To determine the efficacy and cost-effectiveness of routine
      antimicrobial prophylaxis prior to shock wave lithotripsy (SWL) in patients with
      a sterile pretreatment urine culture. METHODS: A structured MedLine search
      revealed eight prospective, randomized, controlled trials (RCTs) of active
      treatment versus placebo or no treatment (n = 885) and six clinical series (non
      RCTs; n = 597) addressing the use of antimicrobial prophylaxis for SWL. A meta
      analysis was performed on the eight RCTs, with the primary outcome being the
      diagnosis of a urinary tract infection (UTI) post-SWL. A cost analysis was
      performed comparing a prophylactic strategy (prophylaxis for every patient and
      treatment for post-SWL UTIs) with a treatment-only strategy for post-SWL UTIs
      using various antimicrobial combinations and the median probability of post-SWL
      UTIs determined by meta-analysis. RESULTS: The incidence of post-SWL UTIs ranged
      from 0% to 28% in the control group and from 0% to 7.7% in the patients who
      underwent prophylaxis. Combining the placebo/no-drug treatment arms in the six
      RCTs by meta-analysis (Bayesian analysis) resulted in a median probability of a
      post-SWL UTI of 5.7% (95% confidence interval [CI] 3.8% to 8.4%). For the drug
      treatment arms, the median probability of a UTI was 2.1% (95% CI 0.9% to 3.6%).
      Relative risk (RR) analysis resulted in an overall RR of post-SWL UTIs with
      prophylaxis versus without prophylaxis of 0.45 (95% CI 0.22 to 0.93) (P =
      0.0005). Depending on the antimicrobial regimen used for prophylaxis and
      treatment, a prophylactic strategy added minimally to the overall treatment cost
      of SWL, and proved cost beneficial when taking into consideration serious UTIs
      requiring inpatient treatment. CONCLUSIONS: A policy of antibiotic prophylaxis
      prior to SWL in patients with sterile pretreatment urine cultures is efficacious
      in reducing the rate of post-SWL UTIs. Discounting inpatient episodes for sepsis
      and acute pyelonephritis, however, the strategy is not cost-effective. In
      contrast, using literature-derived incidence estimates for post-SWL urosepsis or
      pyelonephritis necessitating inpatient treatment, prophylaxis becomes both
      efficacious and cost-effective, and thus constitutes a dominant strategy.

PMID- 9145971
TI  - Additional bacillus Calmette-Guerin therapy for recurrent transitional cell
      carcinoma after an initial complete response.
AB  - OBJECTIVES: To determine the success of additional bacillus Calmette-Guerin (BCG)
      therapy for transitional cell carcinoma recurring after a complete response (CR)
      to the initial treatment course of BCG. METHODS: All patients treated with BCG
      with a minimum follow-up of 5 years were reviewed to identify complete responders
      who subsequently recurred and received additional BCG therapy. The duration of
      initial response and the incidence and duration of a second CR were recorded.
      RESULTS: Of 11 patients with an initial CR to a 6-week course of BCG, 9 (82%)
      achieved a second CR and 5 of the 9 (42%) maintained tumor-free status beyond 5
      years of follow-up (median 87 months, range 64 to 110). Patients who again
      recurred after the second CR did not benefit from further BCG therapy.
      CONCLUSIONS: A repeat course of BCG is a reasonable option of therapy for
      transitional cell carcinoma that has recurred after a CR to a prior course of
      BCG. Careful monitoring by cytology, cystoscopy, and biopsy is mandatory to
      direct nonresponders to prompt alternative therapy and to ensure continued
      disease-free status among responders.

PMID- 9145972
TI  - Risk of concurrent prostate cancer in cystoprostatectomy specimens is related to
      volume of high-grade prostatic intraepithelial neoplasia.
AB  - OBJECTIVES: To assess the relationship of prostatic intraepithelial neoplasia
      (PIN) with both incidental and clinical carcinoma of the prostate. METHODS: We
      retrospectively reviewed prostate histology in 48 men (group 1) who underwent
      surgical removal of the prostate for diagnoses other than prostate cancer, as
      well as in 64 men (group 2) who underwent radical prostatectomies. Both groups
      were assessed for the presence and extent of high-grade (HG-) PIN and compared
      with respect to patient age, Gleason score, and volume of prostate cancer.
      RESULTS: HG-PIN was present in 40 of 48 (83%) group 1 cases. Forty-six percent of
      these cases (22 of 48) had incidental prostate cancer. Twenty-nine of 48 (60%)
      group 1 patients with HG-PIN had multifocal or extensive disease. Twenty of 22
      (91%) incidental prostate cancers were present in 29 prostates with multifocal or
      extensive HG-PIN. In contrast, only 2 of 19 (11%) cases with absent to focal HG
      PIN had prostate cancer. The association of multifocal or extensive HG-PIN with
      incidental prostate cancer was significant (P = 0.001); the relationships of
      extent of HG-PIN and cancer volume (P = 0.06) or high Gleason score (P = 0.017)
      were not significant. HG-PIN was present in 61 of 64 (95%) group 2 cases. The
      associations of extent of HG-PIN and cancer volume (P = 0.169) or high Gleason
      score (P = 0.156) were not significant. CONCLUSIONS: Both the low rate of
      incidental prostate cancer in specimens with absent to focal HG-PIN and the high
      rate of cancer in specimens with multifocal or extensive HG-PIN suggest that HG
      PIN is a marker for concurrent prostate cancer and that the risk of concurrent
      prostate cancer is related to the volume of HG-PIN in the prostate gland.

PMID- 9145973
TI  - Serum creatinine measurements in men with lower urinary tract symptoms secondary
      to benign prostatic hyperplasia.
AB  - OBJECTIVES: To determine the usefulness of routine serum creatinine measurements
      in men with lower urinary tract symptoms secondary to benign prostatic
      hyperplasia (BPH) and to correlate these findings with patient age, symptom
      severity, and comorbid diseases. METHODS: We analyzed serum creatinine
      measurements in 246 consecutive men presenting for evaluation of voiding symptoms
      and BPH. Multiple logistic regression analysis was used to determine whether the
      International Prostate Symptom Score (IPSS), quality-of-life measure from the
      IPSS, patient age, or a history of diabetes mellitus or hypertension predicted
      abnormal creatinine levels. RESULTS: An elevated serum creatinine level was noted
      in 11% (26 of 245) of evaluable patients. Only a history of diabetes or
      hypertension predicted the presence of renal insufficiency. Among men with no
      history of comorbid disease, increasing age was significantly associated with the
      finding of an abnormal creatinine. Neither the overall symptom score nor the
      quality-of-life measure was significantly associated with the likelihood of
      detectable renal dysfunction. CONCLUSIONS: Medical renal disease secondary to
      diabetes or hypertension appears to be the most likely cause of elevated serum
      creatinine measurements in men with BPH and renal insufficiency. We were unable
      to identify subgroups of patients in whom the risk of renal dysfunction is
      sufficiently low to avoid routine serum creatinine measurements.

PMID- 9145974
TI  - High-power (60-watt) potassium-titanyl-phosphate laser vaporization prostatectomy
      in living canines and in human and canine cadavers.
AB  - OBJECTIVES: We studied the safety and efficacy of 60-W potassium-titanyl
      phosphate (KTP) laser prostatectomy in living dogs and compared the efficacy with
      that in fresh human and dog cadavers. METHODS: Ten dogs underwent 60-W KTP laser
      prostatectomy and were sacrificed 3 hours (n = 5) or 7 weeks (n = 5) after
      operation. Two thawed fresh-frozen human cadaver prostates and two thawed fresh
      frozen canine prostates were also vaporized with the 60-W KTP laser. All
      prostates were weighed, measured, serially sectioned, and whole mounted for
      histologic analysis. RESULTS: In dogs, the in vivo procedure was hemostatic, and
      no irrigant absorption was detected. Prostatic defects with a mean diameter of
      3.0 and 2.5 cm at 3 hours and 7 weeks postoperatively, respectively, were
      produced. With experience, resection time was reduced to 14 minutes. Of the 5
      dogs that were studied for 7 weeks, 4 voided immediately after removal of the
      urethral catheter on the morning after operation, and 1 dog required
      recatheterization but voided with a strong stream when the urethral catheter was
      removed 4 days later. All 5 dogs were continent and had normal erectile function
      postoperatively. Defects of 2.0 and 2.5 cm were produced in the two human cadaver
      prostates (weight, 29.5 and 55 g) with resection times of 26 and 54 minutes,
      respectively. Human and canine cadaver prostates required similar energies for
      tissue vaporization (15.2 and 13.7 kJ/cm3 cavity created, respectively, P > 0.6),
      whereas living canine prostates required only 7.0 kJ/cm3 cavity created (P < 0.01
      compared with cadaver tissue). CONCLUSIONS: The 60-W KTP laser allows technically
      easy, safe, rapid, and hemostatic removal of canine prostatic tissue in vivo.
      Furthermore, there is no difference in the efficacy of KTP laser vaporization
      between human and canine cadaver prostates. These findings suggest that KTP laser
      vaporization may be as effective in living human prostates as it is in living
      dogs, and thus it may be a useful technique in the surgical treatment of human
      benign prostatic hyperplasia.

PMID- 9145975
TI  - Color Doppler-guided prostate biopsies in 591 patients with an elevated serum PSA
      level: impact on Gleason score for nonpalpable lesions.
AB  - OBJECTIVES: To compare results of color Doppler-guided ultrasonography (CDUS)
      versus those of systematic biopsies in 591 patients with an elevated serum PSA
      level and to correlate them with digital rectal examination (DRE) findings.
      METHODS: Biopsies were directed into hypervascularized (CDUS+) or
      hypovascularized (CDUS-) hypoechoic peripheral zone nodules (443 cases). When
      transrectal ultrasound (TRUS) was normal (148 cases), biopsies were directed into
      hypervascular area. Six additional posterior biopsies were also performed in
      every patient, together with four anterior biopsies in 117 patients with normal
      DRE and prostate weight above 40 g. RESULTS: Biopsies were positive in 339
      patients (57%). Positive biopsy rate (PBR) of directed biopsies was 84% in
      hypervascular abnormalities (264 of 316) and 17% in hypovascular nodules (23 of
      134) (P < 0.001). PBR of combined biopsies was 84% in CDUS+ patients (266 of 316)
      and 26% in CDUS- patients (73 of 275) (P < 0.001). Comparison of TRUS and CDUS
      showed a sensitivity of 0.9 and 0.78, respectively, and a specificity of 0.46 and
      0.8, respectively. Of the 131 patients with a PSA level between 4 and 10 ng/mL
      and a normal DRE, PBR was 59% (22 of 37) when CDUS was positive and 11% (10 of
      94) when it was negative, regardless of TRUS abnormalities (P < 0.001).
      Nonpalpable cancers with a negative CDUS showed a significantly (P < 0.001) lower
      Gleason score (5.5 +/- 0.9) than that of CDUS+ cancer (6.5 +/- 1.1). Eleven
      cancers were diagnosed by only anterior positive biopsies. All of them had a
      negative CDUS and a PSA level above 10 ng/mL. CONCLUSIONS: CDUS does not modify
      prostate biopsy policy except in patients with negative CDUS, normal DRE, and PSA
      level between 4 and 10 ng/mL, where deferment of biopsy can be advocated.
      Anterior biopsies are only useful in patients with a PSA level above 10 ng/mL and
      a negative CDUS.

PMID- 9145976
TI  - Role of prostate-specific antigen velocity in prediction of final pathologic
      stage in men with localized prostate cancer.
AB  - OBJECTIVES: Prostate-specific antigen (PSA) velocity prior to radical retropubic
      prostatectomy was evaluated to determine if men with a faster rate of rise in PSA
      have locally more extensive prostate cancer. METHODS: Of 368 men who underwent
      radical retropubic prostatectomy, 82 had two to seven PSA measurements between
      1.3 and 6.7 years before prostate biopsy for evaluation of PSA velocity. PSA
      velocity and the pretreatment parameters of PSA, Gleason score, and T stage were
      evaluated as predictive parameters of pathologic stage. RESULTS: In men with
      pathologically organ-confined disease, PSA velocity was 1.12 ng/mL/yr; in non
      organ-confined cases, it was 1.88 ng/mL/yr. There was a statistically significant
      relationship between a Gleason score of 7 and above and the pathologic extent of
      disease. There was no statistically significant relationship between T stage, the
      PSA at diagnosis, and PSA velocity with respect to final pathologic stage.
      CONCLUSIONS: PSA velocity is not a strong predictor of pathologic stage in men
      with localized prostate cancer.

PMID- 9145977
TI  - Morphologic changes induced by neoadjuvant androgen ablation may result in
      underdetection of positive surgical margins and capsular involvement by prostatic
      adenocarcinoma.
AB  - OBJECTIVE: Neoadjuvant androgen ablation (NAAA) causes significant
      cytoarchitectural changes in both benign and malignant prostatic epithelial cells
      that may contribute to underdetection of prostate cancer capsular involvement and
      positive surgical margins. METHODS: The aim of this study is to determine the
      ability of cytokeratin immunohistochemistry to enhance the determination of
      pathologic stage of prostate cancer following NAAA. RESULTS: Cytokeratin AE1/AE3
      immunohistochemistry identified 6 (27.3%), 15 (68.2%), 5 (22.7%), and 5 (22.7%)
      cases of organ-confined disease, capsule penetration, positive surgical margin,
      and seminal vesicle involvement, respectively, as compared with 10 (45.5%), 10
      (45.5%), 3 (13.6%), and 5 (22.7%) cases by hematoxylin-eosin (H&E) staining,
      respectively. Two cases without detectable tumor by H&E staining had demonstrable
      residual tumor by cytokeratin immunohistochemical staining. CONCLUSIONS:
      Cytokeratin immunohistochemistry revealed more extensive intracapsular, capsular,
      and extracapsular tumor involvement and higher rate of positive surgical margin
      than did conventional H&E staining. Therefore, the beneficial pathologic effects
      of NAAA observed may, in part, be attributable to the artifact of observation.

PMID- 9145978
TI  - The predictive value of race as a clinical prognostic factor among patients with
      clinically localized prostate cancer: a multivariate analysis of positive
      surgical margins.
AB  - OBJECTIVES: Several investigators have reported that African-American men with
      clinically localized prostate cancer have poorer survival than do white men. In
      addition, prostate cancer in African-American men is commonly diagnosed at a more
      advanced stage of disease. Is race or ethnicity predictive of outcome of
      clinically localized prostate cancer? It has been reported that the presence of
      positive surgical margins significantly influences time to progression
      independently of other prognostic factors. Therefore, we have elected to conduct
      a multivariate analysis of clinical factors including race as potential
      predictors of positive surgical margin outcome. METHODS: We studied 369
      consecutive men (120 African-American and 249 white) who had radical
      prostatectomies at a single institution. Comparisons by race of Gleason score,
      stage, presence of positive surgical margins, and mean preoperative prostate
      specific antigen (PSA) level were carried out. RESULTS: Our data demonstrate that
      African-American men have more pathologically locally advanced prostate cancer
      than do white American men: 69% among blacks compared with 57% among whites.
      However, the difference in rate of positive surgical margins between blacks and
      whites is statistically significant: 58% among blacks versus 40% among whites (P
      = 0.002). Four factors were predictive of positive surgical margins: preoperative
      PSA level, race, clinical stage, and Gleason score. CONCLUSIONS: We have
      demonstrated that race is an independent predictor of positive surgical margins
      among patients with clinically localized prostate cancer and should be included
      in treatment decisions. In addition, the risk of positive surgical margins
      increases noticeably when PSA is greater than 10 ng/mL.

PMID- 9145979
TI  - Comparison of the modified vest and the direct anastomosis for radical retropubic
      prostatectomy.
AB  - OBJECTIVES: This retrospective study was undertaken to compare the efficacy of
      the Vest and direct vesicourethral anastomosis for radical prostatectomy.
      METHODS: Five hundred six patients who underwent consecutive radical
      prostatectomies at our institution were analyzed. Two hundred fifty-nine patients
      underwent vesicourethral anastomosis using the Vest technique and 247 underwent a
      direct suture anastomosis. The groups were analyzed relative to time until
      healing, the occurrence of anastomotic strictures, and the continence rate 1 year
      after surgery. RESULTS: Approximately twice as many patients who underwent the
      Vest procedure experienced delayed healing and 8.5% developed anastomotic
      strictures compared with 1.2% of the direct anastomosis group. The Vest group
      experienced slightly better urinary continence 1 year postoperatively.
      CONCLUSIONS: The Vest procedure is a reasonable alternative to direct anastomosis
      for radical prostatectomy and provides similar results. We suggest specific
      circumstances when the Vest anastomosis may be particularly useful.

PMID- 9145980
TI  - Prostate-specific antigen doubling times in patients who have failed radical
      prostatectomy: correlation with histologic characteristics of the primary cancer.
AB  - OBJECTIVES: This study sought to characterize the postoperative prostate-specific
      antigen (PSA) doubling time and time to biochemical recurrence in patients who
      have failed radical prostatectomy. METHODS: Of 539 consecutive patients who
      underwent radical prostatectomy between 1984 and 1992, postoperative PSA levels
      in 80 initially became undetectable (less than 0.07 ng/mL) before eventually
      increasing, as evidenced by rising PSA levels above the residual cancer detection
      limit of the Tosoh AIA-600 immunoassay run in the ultrasensitive mode (i.e., 0.07
      ng/mL or higher). The PSA doubling time and time to biochemical recurrence were
      calculated for each of the 80 patients and were correlated with the
      histopathologic variables from the operative specimen. RESULTS: Postoperative PSA
      doubling times were predicted by the extent of capsular penetration, percent
      Gleason grade 4 or 5, lymph node involvement, and tumor volume on univariate
      analysis and by capsular penetration, percent Gleason grade 4 or 5, lymph node
      involvement, and patient age on multivariate analysis. Times to recurrence were
      predicted by the presence of positive margins and percent Gleason grade 4 or 5 in
      both univariate and multivariate regression models. The PSA doubling time did not
      correlate with recurrence time. The median PSA doubling time for all patients was
      284 days, and the median time to recurrence was 648 days. CONCLUSIONS: These
      results demonstrate that PSA doubling time and recurrence time are indicative of
      different biologic characteristics of recurrent prostate cancer: Doubling time
      appears to represent the aggressiveness of the original prostate cancer, whereas
      time to recurrence reflects the extent of residual postoperative disease. This
      information should aid in the selection of men who need greater vigilance during
      postoperative surveillance.

PMID- 9145981
TI  - Systematic fine-needle aspiration of the testis: correlation to biopsy and
      results of organ "mapping" for mature sperm in azoospermic men.
AB  - OBJECTIVES: This study compares fine-needle aspiration (FNA) and testis biopsy
      for the ability to detect mature sperm in the testes of azoospermic men. In
      addition, we introduce the concept of testis "mapping" with FNA and apply it to
      detect sperm in men with severe testis failure. METHODS: Sixteen patients were
      evaluated for azoospermia in a university-based infertility clinic. All men had
      testis biopsies and FNAs from matched testicular sites to assess for the presence
      of spermatozoa. Adequacy criteria for FNA specimens were strictly defined, and
      correlative analysis of the two techniques was performed. In addition, a subset
      of 12 men with nonobstructive azoospermia (NOA) had systematic FNA mapping (more
      than four FNA sites per testis) to detect mature sperm for potential clinical
      use. RESULTS: Adequate FNA specimens were obtained in 115 (91.3%) of 126 FNA
      attempts. Of 34 paired biopsy FNA sites. FNA was seen to be more sensitive than,
      and equally specific as, testis biopsy for sperm detection. When compared with
      the biopsy touch imprint, FNA was equally as sensitive and specific. Among men
      with NOA who underwent FNA mapping, 4 (33%) of 12 had localized "patches" of
      sperm detected in areas distant from sperm-negative biopsy sites. In 1 case, a
      pregnancy was achieved with later biopsy and sperm extraction "directed" by
      previous FNA. CONCLUSIONS: For sperm detection, testis FNA provides equivalent or
      better information than a testis biopsy. FNA can localize areas of sperm
      production within the testis and accurately guide sperm extraction procedures in
      men with NOA.

PMID- 9145982
TI  - Functional and radiologic evidence of vascular communication between the
      spongiosal and cavernosal compartments of the penis.
AB  - OBJECTIVES: To investigate the possible communication of the glans penis and
      corpus spongiosum with the corpora cavernosa. METHODS: We performed a functional
      and anatomic study in men with erectile dysfunction. The functional study
      consisted of the injection of alprostadil (10 to 20 micrograms) into the glans in
      17 men while recording intracavernosal pressure (ICP). Once the ICP response had
      stabilized, patients received a second injection of alprostadil by direct
      intracavernosal (IC) administration. For the anatomic study, a spongiogram was
      performed in 5 patients by the injection of radiologic contrast into the glans.
      RESULTS: Injection of alprostadil into the glans caused tumescence of the glans
      and corpus spongiosum, followed by tumescence of the corpora cavernosa with an
      increase in ICP from 9 +/- 2 mm Hg (mean +/- SD) at baseline to a peak response
      of 50 +/- 25 mm Hg. Subsequent IC injection of alprostadil, on average, increased
      ICP by only 5 mm Hg (a 15% increase) above the response to injection in the
      glans. The spongiogram demonstrated drainage of the glans into the deep dorsal
      vein, as well as drainage of the spongiosum into the circumflex veins, which in
      turn drained into the deep dorsal vein. Filling of the corpora was also
      visualized, suggesting that it occurred in a retrograde manner, through the
      draining venules. CONCLUSIONS: Our study demonstrates that injection of
      alprostadil into the spongy tissue of the glans can provoke erection of the
      corpora cavernosa, and that common channels for the drainage of the glans, corpus
      spongiosum, and corpora cavernosa are most likely the route for drug transfer
      from the spongiosal to the cavernosal compartment.

PMID- 9145983
TI  - Laparoscopic surgery in children with ventriculoperitoneal shunts: effect of
      pneumoperitoneum on intracranial pressure--preliminary experience.
AB  - OBJECTIVES: We monitored changes in intracranial pressure (ICP) in 2 children
      with myelodysplasia undergoing laparoscopic bladder autoaugmentation. Both
      children had ventriculoperitoneal shunts (VPS) secondary to Arnold-Chiari
      malformations (type II). METHODS: ICP was monitored through a 23-gauge needle
      placed into the shunt reservoir and connected to a pressure transducer and
      drainage system. Intraoperative mean arterial pressure, end-tidal CO2 (ETCO2),
      ICP, abdominal pressure, and cerebral perfusion pressures were all monitored.
      RESULTS: Both children demonstrated rapid onset and sustained increases in ICP of
      greater than 12 mm Hg above baseline to a maximum pressure of 25 mm Hg. The
      average cerebrospinal fluid removed from each patient was 30 cc, thereby lowering
      ICP with no adverse neurologic sequela. The pCO2 remained constant throughout the
      procedures, as measured by ETCO2. CONCLUSIONS: We believe that intracranial
      hypertension (IH) results from a "Valsalva-like" phenomenon, which causes
      cerebral vascular engorgement. In addition, the pneumoperitoneum may increase the
      resistance to outflow through the distal peritoneal catheter, causing a partial
      or complete shunt obstruction. Untreated IH may result in adverse neurologic
      sequelae from brain herniation in these children with hindbrain anomalies and
      potentially altered brain compliance. We believe it is prudent to perform
      intraoperative ICP monitoring in this subgroup of patients undergoing
      laparoscopic surgery and that IH should be treated by ventricular drainage.

PMID- 9145984
TI  - Management of neurogenic fecal incontinence in myelodysplastic children by a
      modified continent appendiceal stoma and antegrade colonic enema.
AB  - OBJECTIVES: Antegrade colonic enemas for neurogenic fecal incontinence via
      reverse reimplanted appendices (Mitrofanoff principle) have been primarily
      reported by Malone and coworkers in 1990. We used a modification of the described
      surgical technique and treated the first 10 patients with neurogenic fecal
      incontinence due to spina bifida. The surgical procedure and the results are
      reported. METHODS: Since November 1991, we have used a surgical procedure similar
      to the appendiceal continence mechanism in urinary diversion to establish a
      continent colonic cutaneous stoma for antegrade enemas in 10 myelodysplastic
      patients (4 females, 6 males; median age 13.2 years [range 6 to 26]) with severe
      neurogenic fecal incontinence. The average follow-up is now 26.4 months (range
      12.5 to 50). All patients had neurogenic bladder dysfunction successfully managed
      by clean intermittent catheterization, anticholinergic drugs, or artificial
      sphincter implantation. The surgical technique for fecal incontinence included
      the partial orthotopic submucosal imbedding of the appendix into a cecal tenia
      and the fixation of the ileocecal region at the inner side of the abdominal wall
      after creation of an appendicocutaneous catheterizable stoma. RESULTS: All
      patients reached fecal continence for at least 38 hours (median 45.3) by using
      antegrade colonic enemas with 1.5% saline solution (n = 9) or GoLYTELY solution
      (n = 1), 0.5 to 1.5 L every 2 to 3 days. All other therapies (diet, oral
      medication, rectal purgative, or enema) to reach fecal continence had previously
      failed. There were only two complications seen at the follow-up. One boy with an
      artificial urinary sphincter presented with infection of the sphincter system,
      which led to explantation. Another boy presented 15 months after creation of the
      colonic appendiceal stoma with saline intoxication possibly due to a homemade
      saline solution. CONCLUSIONS: We conclude that the antegrade colonic enema via an
      orthotopic continent appendiceal stoma is a safe and highly effective treatment
      modality for fecal incontinence in patients with neurogenic bowel dysfunction if
      nonsurgical management has failed.

PMID- 9145986
TI  - Facilitated radical perineal prostatectomy with the Brooke Bookwalter retractor
      blade.
AB  - With the resurgent interest in radical perineal prostatectomy, a variety of
      enhancements have been made to the procedure. We describe herein the use of a
      retractor blade that allows full mobilization of the seminal vesicles and vasa
      prior to prostatic apical dissection, thus facilitating bladder neck-sparing
      radical prostatectomy. This retractor system dramatically improves visualization
      of the seminal vesicles and prostatic pedicles, allowing a single surgeon to
      perform this procedure easily.

PMID- 9145985
TI  - Scrotal fixation: a different surgical approach in the management of the low
      undescended testes.
AB  - OBJECTIVES: To evaluate the feasibility of using the scrotal approach in patients
      with undescended testes. METHODS: Over an 18-month period, 165 patients were
      diagnosed to have 208 undescended testes. Of these, 28 were nonpalpable. RESULTS:
      At exploration, 7 testes were abdominal, 33 were canalicular, 165 were in the
      region of the external ring/pubic tubercle, and 1 was perineal. There were 2
      cases of unilateral monorchism. The operative procedure performed was as follows:
      orchiectomy for 6 abnormal testes, orchiopexy for 142, and scrotal fixation (SF)
      for 58. (In this series, 9 patients were converted from SF to an orchiopexy at
      the time of the initial operative procedure.) SF involves a scrotal incision
      extending down to the tunica vaginalus. The cord is then mobilized from below,
      after which the testis is placed in an extra-dartos pouch. CONCLUSIONS: Our study
      has shown that there are a significant number of undescended testes that lie in
      the region of the pubic tubercle, lack a hernial sac, and can be managed by a
      scrotal mobilization alone. Based on our experience with SF, we have used a
      simple classification of undescended testis that has therapeutic and prognostic
      justifications.

PMID- 9145987
TI  - New technique of vaginal reconstruction following anterior exenteration.
AB  - Vaginal reconstruction is important in sexually active females undergoing
      anterior exenteration for malignant disease. We describe a technique for vaginal
      reconstruction used in two women who underwent radical cystectomy that required
      en bloc removal of the anterior vaginal wall. A polyglycolic acid mesh with a
      pedicle graft of greater omentum creates the anterior 270 degrees and the apex of
      the neovagina. The technique is simple and adds to the urologist's armamentarium
      of reconstructive procedures that improve quality of life following exenterative
      surgery.

PMID- 9145988
TI  - Double-knotted feeding tube in a child's bladder.

PMID- 9145989
TI  - Hair coil strangulation of the penis.

PMID- 9145990
TI  - Intrarenal pseudoaneurysm presenting 15 years after penetrating renal injury.

PMID- 9145991
TI  - Schistosomal myelopathy as a cause of neurogenic bladder dysfunction.
AB  - Schistosoma hematobium most commonly affects the bladder and S. mansoni has a
      predilection for the liver, spleen, and the mesenteric territories. Schistosomal
      spinal cord involvement is an extremely unusual primary presentation of
      schistosomiasis, especially in the United States. We report 2 patients with
      documented schistosomiasis who presented with urinary incontinence as their chief
      urologic complaint. One patient had no sensorimotor deficit and presented with
      isolated incontinence as the harbinger of spinal involvement. The other patient
      presented 5 years after initial exposure, emphasizing the possibility of a long
      latent period between exposure and onset of symptoms.

PMID- 9145992
TI  - Ketoconazole-induced adrenal crisis in a patient with metastatic prostatic
      adenocarcinoma: case report and review of the literature.
AB  - Ketoconazole has been used with success to treat disseminated intravascular
      coagulation and acute spinal cord compression syndromes associated with
      metastatic prostatic adenocarcinoma. It effects prompt, reversible medical
      castration, making it especially useful as empiric therapy when histologic
      diagnosis is delayed but prostate cancer is suspected. Side effects are usually
      limited to asthenia, nausea, diarrhea, and gynecomastia, but a theoretical risk
      of adrenal suppression exists. We report a case of fulminant adrenal crisis
      precipitated by ketoconazole given on a 6-hour dosing schedule in a patient with
      nerve root compression secondary to prostatic metastases. Through a review of the
      literature, we attempt to provide a better understanding of the use and potential
      dangers associated with ketoconazole therapy.

PMID- 9145993
TI  - Results of Bard BTA test in monitoring patients with a history of transitional
      cell cancer of the bladder.
AB  - OBJECTIVES: To evaluate the sensitivity and specificity of the Bard BTA test
      compared with bladder washing cytology in patients with a history of transitional
      cell bladder cancer undergoing routine follow-up cystoscopy. METHODS: During
      routine follow-up for transitional cell bladder cancer, 75 patients underwent
      cystoscopy, bladder washing cytology, and the Bard BTA test, a latex
      agglutination test that qualitatively detects basement membrane complexes in
      voided urine. From October 1994 to October 1995, a total of 104 Bard BTA test
      examinations were performed. The results of the Bard BTA test were compared with
      those attained with cystoscopy and bladder washing cytology. RESULTS: Cystoscopy
      found tumors in 13 cases. The Bard BTA test was diagnostic in 7 (54%) cases; it
      was more sensitive than bladder washing cytology, which was positive in only 3
      (23%) cases. However, the specificity of the Bard BTA was lower (9% clinically
      unconfirmed positive tests) than that attained with cytology. In 2 patients (2%)
      in whom the cystoscopy was negative, the Bard BTA test was predictive for a
      positive cystoscopy 3 and 5 months later. CONCLUSIONS: The Bard BTA test is a
      noninvasive test that may be an important addition to cystoscopy and cytology in
      the routine surveillance of patients with a history of transitional cell cancer
      of the bladder.

PMID- 9145994
TI  - Inhibition of initial adhesion of uropathogenic Enterococcus faecalis to solid
      substrata by an adsorbed biosurfactant layer from Lactobacillus acidophilus.
AB  - OBJECTIVES: The potency of the Lactobacillus acidophilus RC14 biosurfactant
      "surlactin" to reduce the initial adhesion of Enterococcus faecalis 1131 was
      investigated on a hydrophilic and a hydrophobic substratum in a parallel-plate
      flow chamber, using phosphate-buffered saline and pooled human urine as a
      suspending fluid. METHODS: A parallel-plate flow chamber with a glass or silicone
      rubber bottom plate was filled with different biosurfactant solutions of 0, 0.01,
      0.1, or 1.0 mg/mL for overnight adsorption (18 hours). Subsequently, the adhesion
      of E. faecalis on thus prepared biosurfactant layers was observed in situ in
      phosphate-buffered saline or in urine by automated image analysis. RESULTS:
      Adsorbed biosurfactant layers caused an important, dose-related inhibition of the
      initial deposition rate of E. faecalis and the number of adherent bacteria after
      4 hours on both hydrophilic glass and hydrophobic silicone rubber, although this
      effect was stronger in buffer than in urine. For the experiments carried out in
      urine, the inhibitory effect of the biosurfactant layer was largest when silicone
      rubber was used rather than glass, whereas no influence of the substratum
      hydrophobicity on the inhibition of E. faecalis adhesion was noticed for
      experiments performed in buffer. CONCLUSIONS: The biosurfactant surlactin, as
      released by several Lactobacillus isolates, might open the way to the development
      of antiadhesive biologic coatings for catheter materials. It should be
      considered, however, that these results are preliminary and that the efficiency
      of the biosurfactant is probably affected not only by the hydrophobicity of the
      substratum and the suspending fluid, but also by the type of uropathogen
      involved.

PMID- 9145995
TI  - Radionuclide therapy for prostate cancer lumbar metastasis prolongs symptom-free
      survival in a rat model.
AB  - OBJECTIVES: The present study was initiated to explore the effects of
      hydroxyethylidene diphosphonate labeled with rhenium 186(186Re-HEDP) treatment on
      the progression of lumbar skeletal metastasis in an animal model and to correlate
      the eventual treatment efficacy with the radioisotope tissue distribution.
      METHODS: The effect of 186Re-HEDP on the progression of lumbar metastasis from
      prostate cancer was investigated in the Copenhagen rat model. Metastatic prostate
      tumor deposits were induced in male rats by tail vein injection of R3327-MATLyLu
      prostate tumor cells under concomitant clamping of the inferior caval vein. The
      development of clinical symptoms such as onset of hind leg paralysis and urinary
      bladder swelling was monitored and related to the presence of tumor cells within
      histologic sections of L-5 and L-6 vertebrae. RESULTS: The 186Re-HEDP
      administration, given either 1 day or 8 days after surgical induction of lumbar
      metastasis, could significantly increase the symptom-free survival of the
      animals. These results were confirmed by a significant decrease in the presence
      of histologically detectable tumor tissue. Biodistribution studies demonstrated
      the uptake of the major part of the radioisotope within bone tissue. Uptake of
      radioactivity within the lumbar vertebrae on a microscopic scale, as shown by
      phosphor screen autoradiography, was concentrated in areas of bone formation and
      turnover. Signs of radiotoxicity, such as bone marrow replacement by fat cells
      and the absence of megakaryocytes, were observed. CONCLUSIONS: The results show
      that radionuclide treatment using 186Re-HEDP is a potentially efficacious
      treatment option in prostate cancer disseminated to the skeleton. The optimal
      treatment dose should be determined carefully and aimed at acceptable levels of
      myelotoxicity.

PMID- 9145996
TI  - Modulation of feline bladder and distal urethral responses to dorsal sacral root
      stimulation by intrathecal administration of a kappa 1-opioid agonist.
AB  - OBJECTIVES: We examined bladder and distal urethral responses to sacral dorsal
      root (SDR) electrostimulation with simultaneous intrathecal administration of a
      kappa 1-opiate agonist. METHODS: Experiments were conducted on 14 spinally intact
      and 6 chronic spinally transected decerebrated mongrel cats. In the chronically
      spinalized cats, midthoracic complete spinal cord transection was performed 6 to
      8 weeks before the electrostimulation experiments. Sympathetic denervation was
      carried out by cutting the sympathetic chain and the hypogastric nerve
      bilaterally. Proximal ends of the cut S1-3DR were stimulated, and bladder
      pressure and urethral perfusion pressure changes were recorded before and after
      drug administration. RESULTS: The S2DR electrostimulation in spinally intact cats
      produced the best vesical contraction, but with dyssynergic urethral response.
      The magnitude and the pattern of the response changed with the different
      stimulation parameters. U-50,488H, a selective kappa 1-opiate receptor agonist,
      decreased significantly the bladder and the urethral responses to S2DR
      stimulation in spinally intact but not in chronic spinally transected cats. Nor
      BNI, a kappa antagonist, reversed these responses in spinally intact cats.
      CONCLUSIONS: Our results showed that it is feasible to produce bladder
      contraction with SDR stimulation and suggest that kappa 1 receptors may have a
      role in bladder and distal urethral reflexes at the suprasacral level.

PMID- 9145997
TI  - Epidemiology of interstitial cystitis.
AB  - OBJECTIVES: To discuss what is currently known about the population prevalence of
      interstitial cystitis (IC) and demographic characteristics of IC patients.
      METHODS: Changes over time in the criteria for diagnosis of IC are described. The
      3 published studies of the population prevalence of IC are reviewed.
      Epidemiologic issues important in the design of studies of IC are cited. RESULTS:
      IC is a disease of chronic voiding symptoms. There is very little reliable
      information published on the etiology, risk factors, or number of persons
      affected. The criteria used for diagnosis of IC by different investigators have
      been variable. In 1988, research criteria for a case definition of IC were
      published, to be applied for IC patients enrolled in National Institutes of
      Health-funded studies. Three published studies of the population prevalence of IC
      are available. Each study used different criteria for defining a case of IC, and
      none used the NIH research criteria to define a case. Prevalence estimates for IC
      vary significantly, from 10 cases/100,000 reported in Finland in 1975, (based on
      hospital record review), to 30/100,000 in the United States in 1987, (based on a
      mailed survey of board certified urologists), to 510 cases/100,000 in the United
      States in 1989, (based on participant self-report in the 1989 National Health
      Interview Survey). It is unclear the extent to which these estimates represent
      true differences in prevalence, rather than reflect the different methods used to
      define an IC case. Several investigators have reported demographic
      characteristics of the IC patients followed in their clinics. All studies of
      adults show a marked female predominance, with reported onset of symptoms
      generally in the middle years of life. Patients may experience a delay of years
      from the onset of symptoms to the time of definitive diagnosis. The natural
      history of symptoms of IC has been reported to be that of a subacute onset with a
      rapid peak in severity, and then a relatively constant plateau of chronic
      symptoms thereafter. However, many patients do experience remissions and flares
      in their disease symptoms. CONCLUSIONS: Few therapies for IC have been evaluated
      using rigorous epidemiologic methods. Many questions remain to be answered. New
      studies of IC should include epidemiologic consultation at the stage of study
      design.

PMID- 9145998
TI  - A collaborative approach to managing interstitial cystitis.
AB  - OBJECTIVES: To establish that conventional protocols often do not provide an
      adequate framework for managing interstitial cystitis, and to describe the
      special role of the urologic caregiver in developing a collaborative relationship
      with interstitial cystitis (IC) patients that can allay fears and provide hope
      that this devastating disease can be managed effectively. METHODS: Epidemiologic
      studies and a decade of experience of IC patients and their physicians are
      utilized in developing a rationale for a collaborative relationship between
      urologic caregivers and IC patients. RESULTS: The symptoms of interstitial
      cystitis-pain, urgency, and urinary frequency-can have a profoundly disruptive
      effect on patients' lives and present unique challenges to physicians as urologic
      caregivers. The impact of IC on patients' lives needs to be accounted for
      empathetically, and appropriate referrals for depression, sexuality, or
      relationship problems should be made. Pain should be managed aggressively, and
      patients who have had delayed diagnosis or who have not responded to the
      traditional treatments should be educated about the array of medical,
      complementary/alternative, and self-help modalities available. CONCLUSIONS: A
      successful treatment paradigm requires that physicians and patients be
      knowledgeable about the array of medical and complementary/alternative therapies
      and that these be applied in a systematic but creative way. Through empathic
      support, information, and a flexible treatment protocol, patients will learn to
      trust the medical process and take an active part in the management of IC.

PMID- 9145999
TI  - Interstitial cystitis: a critique of current concepts with a new proposal for
      pathologic diagnosis and pathogenesis.
AB  - Interstitial cystitis (IC) has continued to be an unresolved problem in clinical
      urology despite intense investigation over the past 16 or more years. Its
      etiology and pathogenesis are still undetermined, and its pathologic diagnosis is
      essentially one of exclusion, with no specific or clear criteria. In this review,
      current concepts of the etiology/pathogenesis and pathology are critically
      analyzed, new pathologic observations summarized, and a proposal of neurogenic
      inflammation as the primary pathogenetic factor is presented in the context of
      all currently available information. The popular postulate attributing IC to a
      deficient or defective glycosaminoglycan urothelial surface layer is not
      substantiated by morphologic, experimental, clinical, or therapeutic
      observations. Although the consensus seems to discount an infectious etiology,
      there is sufficient evidence that a microbial factor-short of a bona fide
      clinical infection-may have a role. Both autoimmunity and mast cell infiltration
      also appear to have a role, despite the lack of evidence that either is involved
      as the primary etiologic factor. Claims that the so-called feline urologic
      syndrome may represent a natural animal model of IC are shaky. As it now stands,
      there is no natural or induced animal model that duplicates IC as it occurs in
      humans. No specific or diagnostic light microscopic pathologic features are
      provided by either routine histopathology or immunohistochemistry. Increasingly,
      it has been recognized that detrusor mast cell count has little or no diagnostic
      value. On the other hand, electron microscopy has provided important new
      observations: (a) presence of mast cells, activated by piecemeal degranulation,
      in close proximity to intrinsic nerves-particularly in suburothelium: (b)
      distinctive pathologic changes in urothelium, suburothelium, and muscularis in
      biopsy samples obtained after diagnostic bladder hydrodistension; (c) constant
      associated changes in venules, capillaries, and neural elements in the same
      biopsy samples; and (d) diffuse involvement of bladder wall, with the most
      evident and profound pathologic changes in posthydrodistension biopsy samples
      obtained from cystoscopically obvious lesions (glomerulations). These features
      are sufficiently distinctive to allow definitive pathologic diagnosis of IC, and
      provide a firm basis for primary involvement of neurogenic inflammation in its
      pathogenesis. A proposal is presented regarding the mechanisms invoked by
      neurogenic inflammation. This proposal revolves around sensory nerve excitation,
      the release of neuropeptides, and activated differential secretion of potent mast
      cell mediators. This proposal can account for the heterogeneity and variability
      of observed pathologic features, and upholds the tacit acceptance of IC as a
      disease of pluricausal etiology and multifactorial pathogenesis.

PMID- 9146000
TI  - Mast cells and nerve fibers in interstitial cystitis (IC): an algorithm for
      histologic diagnosis via quantitative image analysis and morphometry (QIAM).
AB  - OBJECTIVE: To develop and evaluate a diagnostic algorithm based on the alteration
      of mast cell and nerve fiber observed in bladder tissue of patients with
      interstitial cystitis (IC). MATERIALS AND METHODS: Non-IC samples from 6 control
      groups (N = 10, 10, 13, 2, 11, and 3, respectively) and nonclassic interstitial
      cystitis (NC-IC, N = 20) were stained with Giemsa stain in order to calculate the
      detrusor to mucosa mast cell ratio (DMMCR) using quantitative image analysis and
      morphometry (QIAM). Immunohistochemical staining for S-100 protein was also
      performed to quantify nerve fiber proliferation in the detrusor muscle of the
      bladder. RESULTS: The average DMMCR of NC-IC was 1.19. Bacille Calmette-Guerin
      (BCG) cystitis was 0.84 and microscopically normal bladder tissue from patients
      with bladder or prostate cancer was 0.45. No case of IC that we examined had a
      DMMCR < 0.5. The number and percentage area of nerve fibers in the detrusor in IC
      were increased compared to controls and BCG (IC, 2.01%; BCG, 0.95%; control,
      1.3%). CONCLUSION: A diagnostic algorithm is proposed for IC based on the
      findings that indicate that: 1) if the DMMCR > 0.75, then IC is present; 2) if
      the DMMCR < 0.5, then IC is negative; and 3) if the DMMCR is between 0.5 and
      0.75, a quantitative S-100 protein staining analysis can be employed to evaluate
      nerve fiber proliferation to detect those marginal cases of NC-IC. The findings
      of the study also suggest that a neuroimmune process or mediation may be involved
      in the pathogenesis of IC.

PMID- 9146001
TI  - Do infectious agents cause interstitial cystitis?
AB  - The possibility that infectious agents play a role in the etiology of
      interstitial cystitis (IC) has been investigated for a number of years. Early
      studies were directed toward attempts to cultivate bacteria and fungi on routine
      culture media and microscopic examinations of urine or bladder tissue specimens
      for the presence of microorganisms. In more recent years, this approach has been
      expanded to include sophisticated culture techniques to search for the presence
      of fastidious and unusual organisms that would not be detected by routine culture
      methods. Similarly, the presence of viruses has been sought by incubating
      specimens from interstitial cystitis patients in mammalian cell cultures to
      detect cytopathic effects. None of these approaches has provided convincing
      evidence that micro-organisms or viruses are associated with IC. The latest
      attempts to search for the presence of bacteria have made use of the polymerase
      chain reaction (PCR) to amplify bacterial 16S rRNA genes that would be present if
      bacteria were present in bladder tissue or urine of IC patients. This approach
      allows bacteria to be detected and even identified without culture. However, the
      results from the great majority of bladder biopsy samples analyzed by these
      molecular techniques have been negative. PCR strategies have also been used to
      search for the presence of certain viruses in IC specimens, again without
      success. At this time, the results from laboratory culture, light and electron
      microscopy, and various molecular strategies to detect micro-organisms and
      viruses in IC specimens all argue against an infectious etiology for IC.

PMID- 9146002
TI  - Interstitial cystitis: unexplained associations with other chronic disease and
      pain syndromes.
AB  - OBJECTIVE: To determine the prevalence of concomitant disease in individuals with
      interstitial cystitis and to compare these results to the general population.
      METHODS: We used a questionnaire-based study evaluating 12 disease processes and
      a survey of interstitial cystitis characteristics. The population was 2,405
      individuals with interstitial cystitis who responded to the initial survey and an
      additional 277 individuals who were randomly selected and individually contacted.
      RESULTS: Allergies, irritable bowel syndrome, and sensitive skin were the most
      common diseases in the interstitial cystitis population. In comparison to the
      general population, individuals with interstitial cystitis are 100 times more
      likely to have inflammatory bowel disease and 30 times more likely to have
      systemic lupus erythematosus. In addition, allergies, irritable bowel syndrome,
      sensitive skin, and fibromyalgia have an increased association with interstitial
      cystitis. CONCLUSIONS: Interstitial cystitis has, as yet, an unexplained
      association with certain other chronic disease and pain syndromes.

PMID- 9146003
TI  - The interstitial cystitis symptom index and problem index.
AB  - OBJECTIVES: To develop 2 brief self-administered indices for measuring lower
      urinary tract symptoms and their impact in patients with interstitial cystitis
      (IC). METHODS: An initial set of questions was developed and evaluated in focus
      groups. The index was revised, shortened, and validated with patients diagnosed
      in 3 large urologic practices with experience in interstitial cystitis (N = 45).
      Controls were recruited from a group of healthy volunteers in a gynecology clinic
      (N = 67). Internal consistency, construct validity, and test-retest reliability
      were evaluated. RESULTS: The IC symptom index and the IC problem index measure
      urinary and pain symptoms and assesses how problematic symptoms are for patients
      with interstitial cystitis. Psychometric performance of both instruments is good,
      with the symptom index demonstrating excellent ability to discriminate
      characteristics between patients and controls. CONCLUSION: Both indices should be
      useful in the evaluation and management of patients with IC and should be
      particularly useful in clinical trials of new therapies for this condition, where
      reliable, validated, and reproducible outcome measures are critically important.

PMID- 9146004
TI  - The Interstitial Cystitis Data Base Study: concepts and preliminary baseline
      descriptive statistics.
AB  - OBJECTIVES: To describe the design, patient population, and data and specimen
      collection aspects of the interstitial Cystitis Data Base (ICDB) Study and to
      provide preliminary descriptive statistics and inferential results from an
      interim analysis. METHODS: All 424 study participants successfully enrolled in
      the ICDB Study prior to December 31, 1995, were selected for an interim analysis
      and were classified into 1 of 3 symptom severity subgroups. Statistical tests for
      associations among these symptom severity subgroups and a broad range of baseline
      characteristics were conducted using Mantal-Haenszel procedures to adjust for
      variation among clinical centers. RESULTS: ICDB Study patients are predominantly
      female (91.5%), white (91.0%), with an average age at enrollment of 44.3 years.
      Nearly 45% of these patients underwent a cystoscopy at baseline screening, among
      whom there was an overall prevalence of 10.5% for Hunner's patch and 90% for
      glomerulations. Urodynamic evaluation for the entire 424 patients demonstrated
      that volumes at first sensation and at maximal capacity were inversely associated
      with symptom severity subgroups. A broad range of symptoms were analyzed,
      indicating that nearly 40% of patients reported urinating 15 times or more during
      awake hours, and more than 20% reported voiding at least 4 times per night.
      Almost half (47.9%) reported constant urgency and 23.6% reported having severe
      pain. Patients in the severe symptom subgroup reported greater limitations in
      selected quality-of-life indicators than those with less severe symptoms.
      CONCLUSIONS: This interim analysis of the ICDB Study data was compared to
      previous epidemiologic studies of IC and provides an essential foundation for
      further analytic investigations of baseline associations and longitudinal trends.

PMID- 9146005
TI  - Associations among urodynamic findings and symptoms in women enrolled in the
      Interstitial Cystitis Data Base (ICDB) Study.
AB  - OBJECTIVES: The goal of this study was to correlate the cystometric findings with
      the presenting symptoms of the 388 women enrolled in the NIH/NIDDK-funded
      interstitial Cystitis Data Base (ICDB) Study as of December 31, 1995. METHODS:
      All patients underwent a complete history and physical and completed standardized
      questionnaires to assess voiding symptoms and quality of life (QOL). A 3-day
      voiding log was also obtained, followed by a baseline urodynamic exam. All
      results are expressed as mean values +/- 1 standard deviation, and all reported
      correlations were significant. RESULTS: A correlation was seen between reported
      daytime, nighttime, and 24-hour frequency, and both volume at first sensation to
      void (VFSV) and maximal cystometric capacity (VMCC). Patients with constant
      severe urgency had smaller VFSV, 63 +/- 59 mL versus 108 +/- 90 mL, and lower
      VMCC, 163 +/- 102 mL versus 288 +/- 135 mL, than patients without the complaint.
      A negative trend was seen for both VFSV and VMCC versus the global severity. An
      inverse trend was seen between minimal and maximal pain scores over the 4 weeks
      before the exam and VMCC. (No correlation existed between current pain noted
      during baseline screening visits and VFSV or VMCC). No urodynamics correlates
      were seen with global measures of body pain and global health. Uninhibited
      detrusor contractions (UDCs) were seen in 56 of 384 patients (14.6%). A positive
      correlation was seen between urgency symptoms and the presence of UDCs.
      Correlations between the VFSV and VMCC were made with both the average voided
      volume (AVV) and the average maximal voided volume (AMVV) as determined by a 3
      day voiding log. Significant positive correlations were seen with each pair-wise
      comparison (P = 0.001). CONCLUSION: These findings confirm that subjective
      measurements of symptoms associated with interstitial cystitis can be confirmed
      objectively with urodynamic studies.

PMID- 9146006
TI  - Associations among cystoscopic findings and symptoms and physical examination
      findings in women enrolled in the Interstitial Cystitis Data Base (ICDB) Study.
AB  - OBJECTIVES: To determine if specific symptoms or physical findings were
      associated with findings on cystoscopic examination under anesthesia in patients
      participating in the Interstitial Cystitis Data Base (ICDB) Study. METHODS:
      Subjects entering the ICDB Study completed symptom questionnaires and underwent
      physical examinations. Additionally, at the discretion of study investigators,
      150 women underwent cystoscopy under anesthesia following a specific protocol of
      bladder distension at 70 to 80 cm irrigating fluid height and reinspection after
      capacity was reached and the irrigant drained. RESULTS: Statistically significant
      (p < 0.01) associations between bodily pain and urinary urgency with the presence
      of a Hunner's patch, and urinary frequency and urgency with a reduced bladder
      capacity under anesthesia were seen. Neither the findings of bloody irrigating
      fluid nor glomerulations were strongly associated with any symptom, and except
      for an association of urethral tenderness with Hunner's patch, no physical
      examination finding was associated with any cystoscopic findings. CONCLUSIONS:
      The strong associations of Hunner's patch and reduced bladder capacity under
      anesthesia with severe pain and urinary urgency, and urgency and frequency,
      respectively, indicate not only the importance of these findings in diagnosing
      interstitial cystitis, but also their potential utility in subclassifying this
      disease.

PMID- 9146008
TI  - Analysis of long-term Elmiron therapy for interstitial cystitis.
AB  - OBJECTIVES: The long-term efficacy and safety of Elmiron (oral pentosan
      polysulfate sodium) in relieving recurring symptoms of interstitial cystitis (IC)
      were investigated in a long-term, open-label physician's usage study. METHODS:
      Patients with diagnosed interstitial cystitis who met the study entry criteria
      received shipments of Elmiron for 3 months at a dose of 100 mg 3 times a day and
      for the consecutive 3-month periods, provided they completed and returned
      questionnaires about their disease symptoms, reported any adverse events, and had
      laboratory data collected before each new shipment. Patients were required to
      purchase the medication. Responses to questionnaires provided the data reported
      here. Several symptomatic parameters of the disease (overall improvement, overall
      improvement in pain and urgency, urinary frequency, and nocturia) were recorded
      in this way and used to evaluate efficacy. RESULTS: Elmiron usage was correlated
      with improvements in some symptoms, and these improvements increased with
      duration of treatment. Some symptoms were improved within 5 months, although most
      continued to show improvements in both severity rating and in percentage of
      positive responders over 1 to 2 years. Populations of patients receiving extended
      treatment, some for > 90 months, showed no further improvement or worsening in
      symptom values. Forty-six percent of patients dropped out of the study within the
      first 3 months of Elmiron treatment. The frequency of adverse events was < 4%.
      The most notable adverse events were reversible alopecia, diarrhea, nausea,
      headache, and rash. CONCLUSIONS: Elmiron appears to be an efficacious long-term
      treatment for reducing a constellation of debilitating symptoms associated with
      interstitial cystitis in some patients. Patients with a positive response to
      Elmiron appear to maintain this response over time.

PMID- 9146007
TI  - Associations among cystoscopic and urodynamic findings for women enrolled in the
      Interstitial Cystitis Data Base (ICDB) Study.
AB  - OBJECTIVES: Interstitial cystitis is a symptom complex characterized by pelvic
      pain, urinary urgency, urinary frequency, and nocturia. Patients with these
      symptoms, at the 5 clinical centers participating in the National Interstitial
      Cystitis Data Base (ICDB) Study, have been evaluated with history and physical
      exams, questionnaires, and urodynamic studies. METHODS: Of the 388 female
      subjects entered in the study as of December 31, 1995, 150 women have undergone
      cystoscopy with hydrodistension. The data from the endoscopic procedures and the
      urodynamic studies were analyzed. The associations among cystoscopic and
      urodynamic findings were reviewed. RESULTS: Patient demographics of this subgroup
      show a predominance of Caucasians 139/150 (92.7%), with the average age being 43
      (+/-13.2) years. Of the total, 17 patients (11.3%) had a Hunner's patch (HP). The
      prevalence by center varied from a low of 2/38 (5.3%) to a high of 3/9 (33.3%).
      Bloody effluent following hydrodistension was present in 113/150 (75.3%).
      Glomerulations appeared in varying degrees (mild, moderate, severe) in 91.3% of
      the 150 patients. There was a strong inverse relationship (P < 0.001) between
      bladder capacity under anesthesia and the presence of a HP (mean of 845 cc with
      HP absent versus a mean of 531 cc when present). The incidence of HP varied from
      67.6% among women with a bladder capacity at hydrodistension of < 400 cc to 3.8%
      for those with a bladder capacity of at least 800 cc. The presence and increasing
      severity of glomerulations was positively associated (P < 0.003) with the
      presence of HP, ranging from 0/13 (0%) when glomerulations were not present to
      6/31 (19.4%) when glomerulations were graded as severe. Of the patients with HP,
      17/17 (100%) had glomerulations after hydrodistension. HP is more closely
      associated with the moderate to severe range of glomerulations (P < 0.01). Nearly
      half of the patients with HP or 8/17 (47.1%) had "moderate" glomerulations, while
      6/17 (35.3%) had "severe" glomerulations. The volume at first sensation to void
      on urodynamics (mean 87 cc without HP versus 34.7 cc with HP) was highly
      inversely associated (P = 0.002) with the presence of HP, but not with any of the
      other cystoscopic findings. Of patients with HP, 94% had a volume at first
      sensation to void of < or = 50 cc where only 36% of patients without HP had a
      volume at first sensation to void of < or = 50 cc. The volume at maximum capacity
      on urodynamics was positively associated with the volume at hydrodistension (P <
      0.001). CONCLUSIONS: Overall, patients with HP had lower bladder capacities,
      lower volumes at first sensation to void, and more severe glomerulations. Thus,
      the presence of HP would imply a more severe case of interstitial cystitis.
      Logically, a higher bladder capacity on cystometrogram is associated with a
      higher volume at the time of hydrodistension, and bloody effluent is associated
      with more severe glomerulations.

PMID- 9146009
TI  - Epithelial coating techniques in the treatment of interstitial cystitis.
AB  - OBJECTIVES: To review the newer methods of treatment of interstitial cystitis
      using techniques that coat the epithelium to maintain its integrity relative to
      permeability. METHODS: The technique of employing sulfated polysaccharides in the
      treatment of interstitial cystitis both orally and intravesically were reviewed
      as well as the concepts supporting the use of such technology, including a review
      of the role glycosaminoglycans (mucus) play in the regulation of epithelial
      permeability. Also reviewed were the methods that can be employed to detect
      aberrations of epithelial permeability as seen in the interstitial cystitis
      syndrome. RESULTS: The techniques of detecting epithelial permeability problems
      and appropriate therapy for this using polysaccharides, such as heparin and
      pentosanpolysulfate, are presented. This article also discusses the point that
      these techniques will result in long-term remissions in patients with the IC
      syndrome who respond to these treatments. CONCLUSIONS: The use of sulfated
      polysaccharides, both orally and intravesically, is an effective long-term
      treatment for many people with the interstitial cystitis syndrome.

PMID- 9146010
TI  - Intravesical dimethyl sulfoxide (DMSO) for interstitial cystitis--a practical
      approach.
AB  - OBJECTIVES: To provide a brief overview of intravesical dimethly sulfoxide (DMSO)
      therapy for interstitial cystitis and offer a practical approach to patient
      treatment. METHODS: A review of the literature and a summation of the experience
      with treatment of > 300 patients with DMSO at the Interstitial Cystitis Clinic,
      New England Medical Center. RESULTS: DMSO is helpful in a significant number of
      patients and it has acceptable morbidity and an excellent safety profile.
      CONCLUSIONS: Intravesical DMSO (singly or in combination) is one of the mainstays
      in the pharmacologic treatment of interstitial cystitis.

PMID- 9146011
TI  - Hydroxyzine therapy for interstitial cystitis.
AB  - OBJECTIVES: To determine the usefulness of oral hydroxyzine for the treatment of
      symptomatic interstitial cystitis. METHODS: This study was an open-label,
      nonconsecutive case series of patients treated by their local physicians, in
      consultation with the authors. A case-report form using visual analog scales was
      used to assess outcomes. RESULTS: Out of 140 patients, 90 (65%) returned the case
      report forms. A 40% reduction in symptom scores was reported. This rose to 55% in
      patients with a history of allergies. CONCLUSIONS: Hydroxyzine is a useful drug
      for the symptomatic treatment of IC, especially in patients with documented
      allergies and/or evidence of bladder mast cell activation.

PMID- 9146012
TI  - Intravesical hyaluronic acid in the treatment of refractory interstitial
      cystitis.
AB  - OBJECTIVES: On the assumption that interstitial cystitis (IC) is the result of a
      defective mucous lining of the bladder epithelium, a study was carried out to
      investigate the activity of hyaluronic acid (HA) in the treatment of IC. HA is an
      important glycosaminoglycan (GAG) present in all connective tissues, including
      the GAG layer of the vesical mucosa. It exhibits a variety of pharmacologic
      properties that enhance its appeal for the therapy of IC. METHODS: A total of 25
      patients, with the characteristic picture of IC and refractory to other medical
      treatments, participated in a trial of HA. Patients received 40 mg of HA
      intravesically on a weekly basis for 4 weeks, then monthly. Response to therapy
      was evaluated by symptom score, voiding diaries, and visual analog scales.
      RESULTS: An initial positive (complete+partial) response of 56% at week 4
      increased to 71% by week 12. This response was maintained until week 20; beyond
      week 24 there appears to be a moderate decrease in the effectiveness of the
      medication. There was no significant toxicity attributable to the presence of HA
      in the bladder. CONCLUSIONS: The response of refractory IC patients to the
      intravesical administration of HA was gratifying. In the past, many therapies for
      IC that were initially considered promising failed the test of a controlled
      study. Further studies will establish the effectiveness of this particular
      preparation of HA in the treatment of IC.

PMID- 9146013
TI  - Logical and systematic approach to the evaluation and management of patients
      suspected of having interstitial cystitis.
AB  - OBJECTIVES: To outline a systematic approach to the evaluation, diagnosis and
      treatment of interstitial cystitis (IC). METHODS: A review of the literature as
      well as of our experience. RESULTS: The exclusion criteria for the research
      definition of IC can be used as guides when obtaining the history, physical
      examination, laboratory workup, and finally urodynamics and
      cystoscopy/hydrodistension under anesthesia. Once the diagnosis is established,
      patients who are still symptomatic after hydrodistension are treated initially
      with oral medications. Those who do not respond to oral therapy are given
      intravesical therapy. Patients whose symptoms are refractory to both routes can
      be considered for a TENS unit, experimental oral therapies, chronic pain control
      with opioids, or, as a last resort, surgery to create a urinary diversion.
      CONCLUSION: As IC is a diagnosis of exclusion, the evaluation remains one of
      ruling out other disorders that produce similar symptoms in patients whose
      history suggests IC. Until the etiology and pathogenesis of IC are identified,
      specific therapy is not possible. However, symptomatic treatments are helpful in
      the majority of patients.

PMID- 9146014
TI  - [Treatments for chronic sinusitis in children--a study by questionnaire from 433
      hospitals in Japan].
AB  - Information concerning the medical and surgical treatment of pediatric patients
      with chronic sinusitis was obtained through questionnaires from 433 hospitals in
      Japan. The hospitals were authorized as an inservice otorhinolaryngological
      training institute by the Oto-Rhino Laryngological Society of Japan. The
      questionnaires were sent to the hospitals in February, 1995, and answers were
      obtained from 311 hospitals within one month, a 73.5% response rate. Conservative
      therapies were the most common treatment for pediatric sinusitis. The removal of
      hypersecreted nasal mucus by aspiration in combination with alphaadrenergic
      decongestants was performed in 89.1% of the hospitals. Treatment by oral
      administration of drugs was adapted in 88.1%. The administration of antibiotics
      and/or steroids by aerosol was performed in 86.2%. The antral lavage was
      performed in only 17.7%. In the medical treatment, macrolide antibiotics and
      proteolytics enzymes were most frequently administered. Surgical therapy was
      performed if the patient was indicated for surgery in 241 hospitals (77.5%).
      Nasal polyps were removed surgically in 202 hospitals. The intranasal
      ethmoidectomy was performed in 98 hospitals. Five years of age was the youngest
      limit of the surgical indication. In most hospitals, the population of surgically
      treated patients was less than 5% of all pediatric patients with chronic
      sinusitis. Adenoidectomy was adapted for the improvement of chronic sinusitis in
      33.8% of the hospitals.

PMID- 9146015
TI  - [Clinical features of Sjogren syndrome].
AB  - Between 1985 and 1995, 134 patients presented to our clinic with complaints of
      either dry mouth, decreased salivary flow or salivary gland swelling of unknown
      origin. These patients were diagnosed retrospectively based on the criteria
      established by the Sjogren's disease research committee (1977), and 30 patients
      were definitively diagnosed with Sjogren's disease while 23 were considered
      suspect. The gender distribution of these 30 patients was 25 female (83%) and 5
      male (17%). The average patient age was 55.8 years for females and 42.6 years for
      males. Of 30 patients, 10 (33.3%) had only sicca syndrome and the other 20
      (66.7%) had various complications such as collagen diseases, autoimmune diseases,
      and malignant lymphoid infiltration. Subjects included 14 cases of rheumatoid
      arthritis (RA), 1 case of systemic lupus erythematosus (SLE), 1 case of RA with
      periarteritis nodosa (PN), 1 case of progressive systemic sclerosis (PSS) with
      SLE, 1 case of PSS with Hashimoto disease, 1 case of malignant lymphoma and 1
      case of RA with Waldenstrom's macroglobulinemia. Positive blood tests showed a
      relatively high incidence of elevated erythrocyte sedimentation ratios (ESR)
      (75%), elevated IgG levels (69.2%), positive anti-nuclear antibody (52.3%),
      positive anti SS A antibody (75%) and positive anti-SS B antibody (50%).

PMID- 9146016
TI  - [Relationship between distortion product otoacoustic emissions and pure tone
      thresholds in normal and hearing-impaired ears].
AB  - To establish clinical criteria for distortion product otoacoustic emissions
      (DPOAEs) in order to distinguish normal-hearing from hearing-impaired ears,
      DPOAEs were measured and evaluated in 325 normal and 291 cochlear-impaired human
      ears using an ILO92 Otoacoustic Emission Analyzer. The background noise level was
      too variational in each individual ear to ignore in DPOAE measurements.
      Therefore, the value of the difference between the DPOAE amplitude and the
      background noise level (DPOAE noise) was calculated and compared with the pure
      tone threshold at 1 kHz, 2 kHz and 4 kHz. It was difficult, however, to precisely
      separate normal-hearing and hearing impaired ears with DPOAE noise values because
      many normal ears presented small amplitudes of DPOAEs and some impaired ears
      showed high amplitudes. Therefore, cumulative distributions of sensitivity
      (normal hearing ears identified as normal hearing) and specificity (hearing
      impaired ears identified as hearing impaired) were constructed and used to
      calculate a cut off point for DPOAE-noise in order to separate normal hearing
      from hearing impaired ears. It is considered that the cut-off points (DPOAE noise
      values of 7.3 dB at 1 kHz, 10.3 dB at 2 kHz and 16.1 dB at 4 kHz) at which the
      false alarm rates (1 specificity: the rate of hearing impaired ears incorrectly
      identified as normal hearing) correspond to 5% can be useful for clinical
      evaluation of DPOAEs.

PMID- 9146018
TI  - [Clinical features and utricular dysfunction in patients with benign paroxysmal
      positional vertigo].
AB  - We report the clinical features in patients with benign paroxysmal positional
      vertigo (BPPV), who met the following criteria; (1) a history of brief episodes
      of positional vertigo, and (2) a characteristic torsional paroxysmal positional
      nystagmus that was observed visually. The mean age of onset was 55 years. There
      was no sex predominance. In most patients, positional vertigo disappeared within
      2 months. We then used the eccentric rotatory test to examine the patients
      otolithic function. In the eccentric rotatory test, a patient is rotated around
      an axis located behind his head (eccentric rotation, ECR). We have demonstrated
      that the enhancement of vestibulo-ocular reflex (VOR) gain in ECR can be used as
      an index of the utricular function. Enhancement of VOR gain was observed in ECR
      to the lower ear in positional vertigo, but not to the uppermost ear. The
      findings suggest an imbalance in utricular function in patients with BPPV.
      Otoconia dislodged from the deranged utricle may be a source of
      canalolithiasis/cupulolithiasis.

PMID- 9146017
TI  - [Reconstructive surgery for head and neck cancers under multiple facility
      cooperation system].
AB  - The problems with the system for reconstructive surgery for head and neck cancers
      in our department where plastic surgeons are regularly invited from distant
      facilities were discussed. Especially, the importance of preoperative discussion
      between the plastic surgeons and ENT doctors was stressed. The computer system
      with Internet will play an important role in exchanging information such as CT
      scans and MRI scans between the plastic surgeons and ENT doctors. Moreover, the
      establishment of a system to prevent postoperative troubles such as closure of
      anastomosed vessels was stressed. Twenty-seven re-vascularized free flaps had
      been transferred with a 96.3% success rate (26 of 27 cases). We concluded that
      the system for reconstructive surgery under the multiple facility cooperation
      system worked well.

PMID- 9146019
TI  - [Autonomic nervous function in patients with vertigo--evaluation for static
      function, variation and dynamic change using power spectral analysis of RR
      intervals].
AB  - Power spectral analysis of RR intervals (PSA) of 94 vertiginous patients with
      associated autonomic nervous dysfunction (AND group), 31 patients with vertebro
      basilar insufficiency (VBI group) and 25 controls were analyzed in supine and
      upright positions. In addition static function, variation from the supine to the
      upright position and dynamic change in autonomic nervous function (ANF) from the
      supine to the upright position were examined. Heart rate was recorded for 120
      seconds in the supine and 40 seconds in the upright position. RR intervals for
      each 20-second period were computed using FFT (Fast Fourier Transformation), and
      the ratio of low frequency power (0.05-0.15 Hz) to high frequency power (0.15-0.4
      Hz) (L/H) of PSA were analyzed as an index of sympathetic activity. The PSA was
      examined by the following three parameters; L/H at rest during the 80-second
      period from 20 to 100 seconds (static function), the L/H variation between each
      20-second period from 0 to 160 seconds (variation) and the ratio of L/H to that
      in the upright position (dynamic change). The results of PSA were compared with
      those of pulse wave velocity (PWV) and the coefficient of variation of the RR
      interval (CVRR), and association between attacks of vertigo and ANF was
      determined. The results of static function of PSA and the results of PWV and CVRR
      were very similar, indicating that both methods are useful for evaluating ANF in
      vertiginous patients. In the AND group the variation in sympathetic activity
      tended to be larger in patients with sympathetic hyperfunction and
      parasympathetic hypofunction and in the patients with sympathetic hypofunction
      and parasympathetic hyperfunction resulting from PWV and CVRR, than in the
      controls. The dynamic change in patients with sympathetic hyperfunction and
      parasympathetic hypofunction resulting from PWV and CVRR was also significantly
      lower than that in the controls (p < 0.01). Some patients in the AND group
      already showed excessive sympathetic hyperfunction at rest, and changing the
      position from supine to upright might trigger sympathetic hypofunction, causing
      an attack of vertigo. The PSA results in the VBI group were similar to those in
      the controls, suggesting that sympathetic dysfunction did not affect VBI induced
      vertigo.

PMID- 9146020
TI  - [Pediatric neurology and adult neurology].

PMID- 9146022
TI  - [Involuntary movements caused by basal ganglia-disorders and their age
      dependency: introductory remarks].
AB  - The basal ganglia modulate voluntary movements involving the neural circuit of
      the cortex-basal ganglia-thalamus-cortex. The basal ganglia receive all of the
      afferents at the striatum and project the efferents from two output structures,
      the medial segment of the globus pallidus and pars reticulata of the substantia
      nigra. Besides the cortex, the basal ganglia receive inputs from pars compacta of
      the substantia nigra (SNc) and centromedian nuclei of the thalamus. The afferent
      from the SNc is the nigrostriatal (NS) dopamine (DA) neuron and has important
      roles in functional modulation of the basal ganglia. As for efferents, the basal
      ganglia also have output projections to the superior colliculus and pedunculo
      pontine nuclei. In the basal ganglia, the striatum has two efferent pathways; one
      is the direct projection which projects directly to the output structure and the
      other is the indirect pathway which projects to the output structures via the
      lateral segment of the globus pallidus and the subthalamic nuclei, changing
      synapses at these nuclei. The lesions in the basal ganglia show various movement
      disorders or involuntary movements depending on their foci. Basal ganglia lesions
      also develop symptoms age dependently; a certain lesion develops dystonia in
      younger brains, while revealing parkinsonism in adult or older brains. This age
      dependency depends on the difference in the course of the functional maturation
      of each component and pathway of the basal ganglia. At this symposium we tried to
      show the basic pathophysiologies of age dependency by discussing basal ganglia
      disorders in children compared to those in adults and referring to the basic
      science of the basal ganglia.

PMID- 9146021
TI  - [Maternal environment and developmental brain damages].
AB  - To estimate and to prevent the developmental brain damage caused by maternal
      environmental agents, the results were compared between epidemiological and
      experimental studies. I. Ethanol. The features of CNS involvement in human FAS
      (fetal alcohol syndrome) and FAE (fetal alcohol effects) were developmental delay
      and intellectual impairment. In rat FAS or FAE, a beneficial effect of
      supplementary zinc on the fetal cerebrum was observed, but was limited. The
      consistent dysformation of synapses during early brain development may be
      associated with the functional impairment of CNS in FAS and FAE II. Caffeine. A
      reduction in the fetal cerebral weight was observed with caffeine ingestion
      during pregnancy at levels of 1.5-3.0 micrograms caffeine/ml or g wet wt. in dams
      and fetuses. Maternal caffeine disturbs the neonatal cerebrum and produces
      behavioral abnormalities in developing rats. III. X-irradiation. Our study
      provides evidence of the protection by vitamin E of neuronal development in X
      irradiated rat fetuses, through its antioxidant properties, against attacks by
      free radicals and/or lipid peroxide. IV. Low copper level in brain. A teratogenic
      effect of triethylene tetramine dihydrochloride, a chelating drug for copper, on
      the mouse brain was noted, both grossly and microscopically, with a dose of
      higher than 6,000 micrograms/l, which is twenty times as high as the clinical
      treatment dose. V. Tobacco. Thirty-three percent of human FTS (fetal tobacco
      syndrome) cases had CNS involvement, which was characterized by developmental
      delay. Fifty percent or more of FTS children of women who smoked more than 20
      cigarettes per day had CNS involvement. In conclusion, the concomitant effects of
      maternal environmental agents on human brain development should be studied.

PMID- 9146023
TI  - [Pathophysiology of involuntary movements in adults].
AB  - Inhibitory control of basal ganglia output to thalamocortical projection plays an
      important role in normal cortical activity in the current model of the basal
      ganglia motor circuit. Hypokinetic and hyperkinetic movement disorders of basal
      ganglia origin can be explained by excess or collapse of the basal ganglia
      output. An abundance of evidence indicates that parkinsonian akinesia results
      from hyperactivity of the basal ganglia output. Reversal of akinesia by lesions
      of the internal division of the globus pallidus (GPi) or its excitatory source,
      the subthalamic nucleus, agrees with this pathological schema. Ballism associated
      with subthalamic lesions, and dopa-induced dyskinesia are regarded as
      hyperkinetic disorders resulting from suppressed subthalamopallidal projection.
      Decreased firing rate in GPi was reported in both disorders. However, pallidotomy
      has recently been postulated to abolish both ballism and dopa-induced dyskinesia.
      A possible mechanism for the effect of GPi destruction in these hyperkinetic
      disorders may be blockade of the generation or conduction of phasic neuronal
      activities driving choreic movements. Symptomatologically, dystonia has aspects
      of both hypokinetic and hyperkinetic disorders. Overactivity of the premotor
      cortices, which receive projections from the basal ganglia via the ventral
      thalamus, was found both at rest and on movement in idiopathic dystonia. This
      abnormal cortical activity may arise from underactivity of basal ganglia output;
      however, the amelioration of dystonia with pallidotomy suggests a complex
      pathomechanism of the pallidothalamic system in dystonia.

PMID- 9146024
TI  - [The clinical characteristics of involuntary movements in childhood].
AB  - The basal ganglia play important roles in the pathophysiology of various types of
      involuntary movement disorders, such as chorea, ballism, athetosis, dystonia,
      tremor and tics. These involuntary movements when occur in the childhood show the
      specific ages of onset and the courses. For example postural dystonia occurs in
      childhood but action dystonia tend to occur in later ages. Postural tremor occurs
      after the second decades but resting tremor does not occur in childhood.
      Furthermore drug induced dystonia but not levodopa induced dyskinesia occurs in
      childhood. The age dependent clinical features observed in these involuntary
      movements are thought to be due to the specific developmental processes of the
      pathway in the basal ganglia and its efferent projections, which are involved in
      the pathophysiology in the each disorder. For example, the dopamine activity is
      known to be increased in the striatum before ten years of age which decreases,
      rapidly during the first decade and further decreases in the next decade with the
      moderate degree till adult level. The direct pathway, which is predominant in the
      ventral area in the basal ganglia, matures earlier than the indirect pathway,
      which is predominant in the dorsal area. In this paper the pathophysiologies of
      the hereditary progressive dystonia with marked diurnal fluctuation, juvenile
      parkinsonism, idiopathic torsion dystonia, chorea, ballismus and tics, all of
      which occur in the childhood, are discussed from the view point of the age
      dependent specificities of the involved pathways in the basal ganglia and their
      projections during development.

PMID- 9146025
TI  - [Roles of the basal ganglia outputs in movement disorders: a viewpoint based on
      experiences of stereotactic surgery for idiopathic dystonia].
AB  - Ventrolateral (VL)-thalamotomy and posteroventral pallidotomy were carried out in
      37 patients with idiopathic dystonia, including 23 with dystonia musculorum
      deformans, 12 with Meige syndrome and 2 with focal dystonia. There were 11
      patients with the onset age of dystonia below 10 years and 26 with the age above
      11 years. Dystonia tended to generalize in the pediatric patients and to localize
      to the palmo-mental region in the adult patients. VL-thalamotomy in 30 patients
      improved the upper body dystonia especially in the adult patients, but, often
      failed to benefit the pediatric patients. Posteroventral pallidotomy in 18
      patients dramatically alleviated the generalized dystonia especially in the
      pediatric patients. In one adult patient, pallidotomy caused hemiparesis due to
      intracerebral hemorrhage. The internal pallidum projects the efferents to the
      thalamic motor nuclei and also to the brainstem reticular formation that connects
      to the spinal motoneurons. The present findings implicate the descending pallido
      reticular pathway in the mechanism of dystonia of pediatric patients, and the
      ascending pallido-thalamic pathway in that of adult patients.

PMID- 9146026
TI  - [Changes and disorders in voluntary saccades during development and aging].
AB  - We examined age-dependent changes in voluntary eye movements in normal subjects
      (age : 5-76) using a visually guided saccade (V-saccade) task and a memory guided
      saccade (M-saccade) task. Changes were more evident in M-saccades. The latencies
      were long in children (< 12 y.o.) and elderly people (> 50 y.o.). Both young
      children and elderly people tended to break fixation by making a saccade to the
      cue stimulus that indicated the future target position. On the other hand, both
      young children and elderly people tended to be slow in making M-saccade promptly
      after the central fixation point went off. Thus, they had difficulties both in
      suppressing unnecessary saccades and in initiating saccades based on memory.
      Interestingly, similar difficulties were observed, in exaggerated forms, in
      patients in basal ganglia disorders, such as Parkinson's disease, juvenile
      parkinsonism, dopa-responsive dystonia, and hereditary progressive dystonia with
      marked diurnal fluctuation. These findings were consistent with the known
      functions of the basal ganglia which have been revealed by physiological studies
      using trained monkeys. The substantia nigra pars reticulata exerts tonic
      inhibitory influences over the superior colliculus, thereby preventing excitatory
      inputs from triggering unnecessary saccades. The tonic inhibition, however, is
      removed by a phasic inhibition largely originating in the caudate nucleus. Thus,
      inhibition and disinhibition are key mechanisms of the basal ganglia. In fact,
      experimental manipulations of these serial inhibitory pathway in the basal
      ganglia led either to the difficulty in initiation of saccades, especially M
      saccades, or to the difficulty in suppressing unnecessary saccades. These
      comparisons suggest that the functions of the basal ganglia are immature in young
      children while they become deteriorated in elderly people.

PMID- 9146027
TI  - [Involuntary movements and birth injuries to brain].
AB  - Asphyxia may play an important role in the pathogenesis of cerebral palsy (CP) in
      a subpopulation of patients, although this has recently been questioned by some
      investigators. Here I describe the results of our analyses into the involuntary
      movements of children with CP, which resulted from perinatal hypoxic brain
      damages. Based on cranial CT or MRI findings, the patients were divided into five
      groups: A, those showing high density on CT in the basal nuclei (bilateral
      thalami in particular); B, those showing destruction of bilateral putamina; C,
      those with diffuse low-density areas in the cerebral white matter on CT during
      the neonatal period that evolved later into polycystic leukomalacia; D, those
      with similar low-density areas which subsequently resolved; and E, those without
      any pathological findings. Using video records, I demonstrated the motor
      development of six cases with CP. Patients of Group A showed pure athetosis with
      hypotonia. A patient of Group B had severe athetoid CP with spasticity, being
      unable to right his trunk and neck. A case of Group C developed severe spastic
      quadriplegia with athetosis. His mental ability was retained to some extent. In
      Group D, there was moderate spasticity and mild athetosis. A patient with
      transient anxia had disturbance in the coordinated finger movements. Cases with
      choreic movements had no particular CT or MRI findings. Even in the severest of
      these cases, distinction from normal infants was difficult in the very early
      infancy. After four to five months, locomotive prognoses were well predicted by
      the patients' ability to control their trunk. To know more about the pathogenesis
      and CP and to elucidate the significance of involuntary movements, further data
      should be accumulated by clinical observations on motor development, and by
      imaging studies.

PMID- 9146028
TI  - [The clinical study of the first febrile convulsion in children with brain
      damage].
AB  - Forty-nine patients with cerebral palsy, mental retardation, or other congenital
      neurological disorders who had experienced febrile convulsions and had no
      previous nonfebrile seizures were presented. They were followed for 1.6 years to
      15 years (mean: 6.8 years) after the initial febrile convulsion. The incidence of
      subsequent epilepsy (two or more afebrile seizures) was 39%, and 80% of them
      developed epilepsy within 2 years after the first febrile convulsion. The
      paroxysmal discharges on EEG recorded prior to or after the first febrile
      convulsion did not predict the occurrence of later epilepsy. Also under 3 years
      of age, EEG findings led to the same result. There was no definite evidence that
      administration of anticonvulsive drugs prevented later epilepsy. Pre-existing
      neurological abnormality was identified as a risk factor for epilepsy, and was an
      indication of persistent medication. There is no clear prophylactic procedure
      against long-lasting attacks. Accordingly, medical therapy can be started when
      epilepsy has developed. Patients with very severe brain damage who could not move
      except lying comprised only 6% of all cases, and 69% of the epilepsy patients
      were well controlled. They showed a good prognosis as compared with children with
      brain-damage in general with epilepsy.

PMID- 9146029
TI  - [Status of severely mentally and physically handicapped children of school age in
      Nagano prefecture].
AB  - Prevalence rate and etiology were studied in severely handicapped children of
      school age in Nagano prefecture as of July, 1994. Severely retarded children were
      defined as those whose IQ's were lower than 35 and who were unable to walk. The
      total number of severely retarded children was 165. The prevalence rate was
      0.71/1000, 90% of them being in class 1 or 2 of Oshima's classification
      (bedridden or unable to sit alone and with IQ less than 20), and 26% being cared
      for at home. Their average gestational age was 38.5 weeks, and the average
      birthweight 2,772 g. At birth none of them had extremely low birth weight.
      Etiology of the handicaps was classified as follows; congenital 26.1%; maternal
      infection 3.0%; prenatal 3.6%; perinatal 27.3%; postnatal 13.9% and unknown
      26.1%. Asphyxia decreased gradually but the number of low birth weight premature
      infants increased. When postnatal etiologies were excluded, the patients with
      unknown etiology occupied 30.3%, 23.3% of them being light-for-dates baby. The
      examination of the case histories revealed that causes of unknown etiology are
      prenatal. If we add unknown etiology to congenital, maternal infection, and
      prenatal etiology, the prenatal origin is 68%.

PMID- 9146030
TI  - [Rhythmic alpha/theta bursts in the electroencephalogram of early premature
      infants: (1). The features in normal early premature infants].
AB  - Rhythmic alpha/theta bursts were studied on forty-nine electroencephalographic
      records of early premature infants, ranging from 25 to 30 weeks of conceptional
      ages. Frontal alpha bursts and occipital theta bursts were prominent at 25-26
      weeks, and temporal theta bursts prominent at 27-28 weeks. Frontal, temporal and
      occipital alpha/theta bursts were observed unilaterally, when all rhythmic bursts
      were seen frequently. Frontal and temporal bursts appeared often on the left side
      and occipital bursts on the right side.

PMID- 9146031
TI  - [Rhythmic alpha/theta bursts in the electroencephalogram of early premature
      infants: (2). Correlation with background EEG activity].
AB  - Rhythmic alpha/theta bursts were studied on ninety-five electroencephalographic
      records of early premature infants, ranging from 25 to 30 weeks of conceptional
      ages in relation with background EEG activity. When background EEG showed normal,
      frontal alpha bursts and occipital theta bursts were prominent at 25-26 weeks,
      and temporal theta bursts at 27-28 weeks. A significant decrease in all rhythmic
      bursts on the frontal, temporal and occipital areas, was seen in early premature
      infants showing severe background EEG depression. Incidence of rhythmic
      alpha/theta bursts varies inversely with depression of background EEG activity.

PMID- 9146032
TI  - [Developmental dyslexia and dysgraphia--a case report].
AB  - We reported a 7-year-old, right-handed boy whose reading and writing of kana and
      kanji were impaired. He also showed a severe deficit in visuo-spatial perception
      skills. Nevertheless, his ability to read and write kana characters was
      facilitated by means of the Japanese Syllabaries. It is generally considered that
      the Syllabary involve two kinds of language modalities: auditory-verbal and visuo
      verbal language systems. In spite of his intact auditory-verbal language system,
      his visuo-verbal language skills involved in writing kanji were severely
      impaired. It was suggested that a severe deficit of visuo-spatial perception
      skills influenced performance of visuo-verbal language systems. Accordingly, we
      inferred that the patient recalled a kana character by use of the Japanese
      Syllabaries based on his good auditory-verbal language system, and supposed that
      his reading and writing disorders were similar to alexia with agraphia in adult
      patients with angular lesions.

PMID- 9146033
TI  - [A case of hereditary sensory and autonomic neuropathy type IV diagnosed
      following the development of acute encephalopathy due to heat stroke].
AB  - A fourteen-month-old girl, who had shown remittent fever frequently from the
      neonatal period, hypohidrosis, frequent change of face color and self-mutilation
      of the 1st and 2nd fingers of both hands and tongue in the first months of her
      life, developed an acute encephalopathy with generalized tonic convulsion
      outdoors on a sunny hot day. Generalized tonic convulsion subsided within two
      days, but doll's eye phenomenon, loss of pupillary reaction to light, palpebral
      myoclonus, and ballismus of arms and legs followed L-dopa showed some effect on
      the ballismus 1 month after the attack. During the hospital stay, biopsy of sural
      nerve was performed. Morphometric and ultrastructural studies of the sural nerve
      demonstrated decreased numbers of unmyelinated and small myelinated fibers. Skin
      biopsy of the leg revealed sweat glands with no nerve terminals, axons and
      Schwann cells around them. She was diagnosed as having hereditary sensory and
      autonomic neuropathy type IV based on the histological and clinical findings.
      After discharge, bone fracture was found three times without any evidence of
      trauma. Acute encephalopathy, probably produced in relation to the underlying
      neuropathy, was considered to be due to heat stroke.

PMID- 9146034
TI  - [A successful treatment with intravenous high doses of gamma globulin for a minor
      status in a patient with Doose syndrome].

PMID- 9146036
TI  - Development of a stable single-vial formulation for a new technetium complex
      using bilayer lyophilization.
AB  - The interaction between different components used in the preparation of a new
      radiodiagnostic agent, BMS-181321, was overcome by its lyophilization as a
      bilayered product. BMS-181321 is composed of a nitroimidazole ligand BMS-181032,
      that is complexed with technetium-99m just before it is used in radionuclide
      imaging studies. Stannous chloride is required to reduce technetium from the +7
      to the +5 oxidation state before it can be complexed by the ligand. Because BMS
      181032 is unstable in the presence of stannous chloride (when mixed in the liquid
      or solid state), the two components must be contained in separate vials. A
      bilayered lyophile was manufactured, containing the ligand and stannous chloride
      in separate layers in a single vial. The bilayered product was manufactured by
      first filling a solution of the ligand into a vial and freezing the solution. A
      solution containing stannous chloride was then filled into the same vial on top
      of the frozen layer of ligand, and this second layer was also frozen. The two
      frozen layers were then lyophilized to a dry solid cake. The resulting bilayered
      product showed stability comparable to that seen when the ligand and the reducing
      agent were contained in separate vials. The separation provided by the layering
      was sufficient to prevent any significant interaction between the reducing agent
      and the ligand.

PMID- 9146035
TI  - Use of subambient differential scanning calorimetry to monitor the frozen-state
      behavior of blends of excipients for freeze-drying.
AB  - The purpose of this study was evaluation of mannitol and its blends with other
      excipients commonly used as freeze-drying cryoprotectants or bulking agents in
      simulated lyophilization conditions. Subambient differential scanning calorimetry
      (DSC) has been used as an analytical tool to evaluate the phenomena from both a
      qualitative and a quantitative point of view. The DSC scans were performed at
      rates comparable to those generally practicable in industrial lyophilizators.
      During a simulated freeze-drying process, three crystallization events have been
      observed on mannitol solutions: the first two on freezing, and the last one on
      heating. The phenomena are dependent on each other. The addition of other
      excipients can significantly influence this behavior by specifying the
      crystallization of mannitol in freezing or by inhibiting it fully. This means
      that the final physical state of the freeze-dried product (amorphous,
      crystalline, or partially amorphous/partially crystalline) can be tailored by
      accurately choosing not only the freeze-drying conditions but also the
      composition of the solution to be lyophilized. The results point out how the
      physical state of freeze-dried products can be controlled by an accurate choice
      of both excipients and their relative ratios, with the possibility of reducing
      the number of preformulation activities required to design the most appropriate
      formulation for each new drug candidate.

PMID- 9146037
TI  - Sterility and sterility assurance.

PMID- 9146038
TI  - Appropriate specifications at the IND stage.
AB  - Biopharmaceutical product specifications are to be "scientifically sound and
      appropriate." However, how does a biopharmaceutical company determine acceptable
      specifications for its product at the early stages of clinical development? Are
      there really enough test data at the start of the IND trials to "establish"
      specifications? As an industry, are we doing too many tests at the IND stage
      (i.e., the "must do every test on someone's published list" syndrome), and then
      finding that specifications need to be set for each test we run? Are we feeling
      pressured (either by regulatory agencies or by our own corporate cultures) to set
      unrealistic and light specifications at the IND stage, and then later regretting
      having to justify loosening them when we gain more experience with the release
      testing or stability of our products? A discussion on how to set practical
      product specifications for biopharmaceutical products at the IND stage is
      presented.

PMID- 9146039
TI  - Particulate matter determination in LVPs produced in Dutch hospital pharmacies,
      Part 1: Particle-counting accuracy.
AB  - Reproducible particle counting using the light-obscuration technique is often
      troublesome because no absolute standard is available. Therefore, at the
      Laboratory of Dutch Pharmacists the "calibration-in-time" method was developed.
      This method enables checking of the amount of particles counted from a diluted
      latex suspension as a function of time. A particularity of the method is the one
      step dilution procedure. The calibration-in-time method is compared with the
      particle-counting accuracy test according to the USP < 788 >. Advantages and
      disadvantages of both methods are discussed.

PMID- 9146041
TI  - Polymorphic changes of mannitol during freeze-drying: effect of surface-active
      agents.
AB  - The effect of polysorbate 80 on the crystalline properties of mannitol during
      freeze-drying was studied. Crystallinity and polymorphism play an important role
      in, e.g., the solubility and stability of freeze-dried products. Polysorbate 80
      had an effect on both the polymorphism and the crystallinity of freeze-dried
      mannitol.

PMID- 9146040
TI  - Pharmaceutical development of a parenteral formulation of the investigational
      anticancer drug clanfenur.
AB  - A stable parenteral dosage form for the investigational cytotoxic drug clanfenur
      was designed, and the bulk drug was characterized by its nuclear magnetic
      resonance, mass spectrometry, infrared, and ultraviolet spectra. The 1H and 13C
      spectra show clanfenur to be a mixture of two stereoisomers. Because of poor
      solubility in aqueous solution and precipitation in co-solvent, surfactant, or
      emulsion systems, a two-pump infusion system was developed for intravenous
      administration. Clanfenur, solubilized in a Cremophor EL/ethanol (1:1, w/v)
      solution (concentration, 15 mg/mL), can be simultaneously infused with 5%
      dextrose infusion fluid. Total doses of up to 1,680 mg of clanfenur (and 56 g of
      Cremophor EL) theoretically can be administered to patients over a 6-hour period.
      From accelerated stability testing of clanfenur in the Cremophor EL/ethanol (1:1,
      w/v) formulation, a shelf life of 3.5 years at 4 degrees C and of 4 months at 25
      degrees C is calculated.

PMID- 9146043
TI  - [Unfavorable effects of transfusion at the Japanese Red Cross Central Blood
      Center].

PMID- 9146042
TI  - [Regulation of megakaryocyte and platelet production].

PMID- 9146044
TI  - [Heme synthesis and its abnormality].

PMID- 9146045
TI  - [Malignant lymphoma: REAL classification].

PMID- 9146046
TI  - [Growth mechanism of leukemic cells in acute myeloid leukemia].

PMID- 9146047
TI  - [gp-130 related cytokines in mechanisms of myeloma cell growth].

PMID- 9146048
TI  - [Mechanisms of growth and apoptosis in myeloma cells].

PMID- 9146049
TI  - [Role of adhesion molecules on pathogenesis of multiple myeloma].

PMID- 9146051
TI  - [Effect of humanized anti-interleukin-6 receptor antibody on new xenograft model
      of multiple myeloma].

PMID- 9146050
TI  - [Antitumor effect of anti-myeloma cell antibody on human plasmacytoma model].

PMID- 9146052
TI  - [Diagnostic imaging in patients with multiple myeloma: appearance at magnetic
      resonance imaging].

PMID- 9146053
TI  - [Bone lesion in multiple myeloma--bone mineral density measured by dual energy X
      ray absorptiometry in multiple myeloma].

PMID- 9146054
TI  - [Stratification of myeloma patients for improvement of prognosis].

PMID- 9146055
TI  - [Hematopoietic stem cell transplantation for multiple myeloma].

PMID- 9146056
TI  - [Problems in the treatment of multiple myeloma].

PMID- 9146057
TI  - [Measurement of blood loss and bleeding pattern from the bleeding time incision].

PMID- 9146058
TI  - [Platelet aggregometry based on the particle counting method using light
      scattering].

PMID- 9146059
TI  - [Basic mechanisms and clinical implications of shear-induced platelet
      aggregation].

PMID- 9146060
TI  - [The significance of APC resistance in eastern Asia].

PMID- 9146061
TI  - [Assay methods and their significance of factors involved in tissue factor
      dependent coagulation reaction].

PMID- 9146062
TI  - [Platelet aggregate formation in peripheral blood anti-coagulated with sodium
      heparin is facilitated by mixing].
AB  - Peripheral blood anti-coagulated with sodium heparin (25 U/ml) form 60 healthy
      volunteers invariably had a reduced platelet count, when whole blood was mixed in
      the presence of air. Smear findings similar to those observed in EDTA-induced
      pseudothrombocytopenia and the counteracting effect of prostaglandin E1 (1
      microM) on thrombocytopenia suggest that this thrombocytopenia is due to platelet
      activation and aggregate formation. Mixing may activate platelets, because the
      extent of thrombocytopenia had a positive correlation with the air volume and
      mixing intensity. Aspirin (1.8 mM) and 5-HT2 blocker (sarpogrelate 100 microM)
      also inhibited this phenomenon. These findings suggest that the mechanism of
      platelet activation might be partly related to arachidonate metabolism and
      serotonin release. Oxygen appears to have no direct effects. It is suggested that
      red blood cells and/or white blood cells participate in platelet activation,
      because platelet aggregation of platelet-rich plasma was less than that of whole
      blood. 5-lipoxygenase inhibitor had little effect. To measure platelet counts, it
      appears essential to eliminate the copresence of air in blood samples anti
      coagulated with heparin.

PMID- 9146063
TI  - [Possible role of immunocompetent cells on periodic exacerbation of idiopathic
      thrombocytopenic purpura].
AB  - A 44 year-old man was admitted to our hospital in October, 1992 with epistaxis.
      Fifteen months before admission, thrombocytopenia had been pointed out, but he
      had no bleeding episode. At admission, neither hepatosplenomegaly nor lymph node
      swelling was observed. Hematological findings were as follows; WBC
      10,000/microliter, Hb 14.0 g/dl, PLT 5,000/microliter, including giant platelets.
      Platelet associated IgG (PAIgG) was 471 ng/10(7) cells. Bone marrow aspiration
      revealed normocellularity with moderate increase in the number of mature
      megakaryocytes, but no dysplastic changes were seen. Biochemical and radiological
      examinations disclosed neither malignant diseases nor autoimmune diseases. Based
      on the diagnosis of idiopathic thrombocytopenic purpura, danazol therapy (300
      mg/day) was started in November, 1992. After initiation of treatment, the
      platelet count changed cyclically every 4 weeks. To elecuidate the mechanism of
      this phenomenon, we periodically evaluated the patient's immunological
      background. T lymphocyte counts and subset proportions remained almost the same
      through out the course, whereas NK cell counts and NK activity coincided with the
      change of the platelet count. These results suggest that in this case NK cells
      may play a role in the cyclic fluctuation of platelet count by regulating the
      immune system.

PMID- 9146065
TI  - [Autosomal dominant distal myopathy with rimmed vacuoles and cytoplasmic
      inclusions: report of a family].
AB  - We reported four patients with distal myopathy in the same family. Muscle
      weakness and atrophy started in the lower extremities, especially in the calf
      muscle, and it extended to the upper extremities and pelvic muscles to a variable
      extent. Facial and bulbar muscles were slightly involved in one case. The
      anterior tibial muscle tended to be better preserved than the calf muscle.
      Cardiac abnormalities were absent in any case. Serum creatine kinase activity was
      normal or mildly elevated. Skeletal muscle biopsies revealed myopathic process
      presenting rimmed vacuoles, eosinophilic cytoplasmic inclusions and/or
      subsarcolemmal mass. Ultrastructurally, cytoplasmic inclusions were composed of
      electron dense granular material and intermediate-sized filaments. There were
      membranous whorls and myelin-like figures which were the characteristic findings
      of rimmed vacuoles. Immunohistochemistry revealed accumulation of desmin,
      dystrophin and vimentin in the cytoplasm of degenerating muscle fibers and in the
      inclusion. In present patients, cardiac function was normal and the tibialis
      anterior muscle was relatively spared. These features were different from the
      autosomal dominant rimmed-vacuolar myopathy with desmin storage described in
      previous reports.

PMID- 9146064
TI  - [Extramedullary plasmacytoma with multiple metastasis following a maxillary
      plasmacytoma].
AB  - A 67-year old man noticed swelling of left maxillary in October 1992. Surgical
      biopsy of the left maxillary tumor revealed the plasmacytoma at the department of
      oral surgery. The Tumor disappeared after radiation therapy. He was admitted with
      dizziness and tarry stool in June 1994. We found left cervical and abdominal
      paraaortic lymph node swellings by the computer tomography. He died inspite of
      chemotherapy in December. Autopsy showed that plasma cells diffusely and
      nodularly invased in all alimentary tract with multiple ulcerations. Invasion was
      also observed in the liver, lungs, thyroid, heart, kidneys, and adrenals. The
      plasma cells in the liver showed IgG kappa type by tissue immunostain. Diffuse
      invasion of extramedullary plasmacytoma is very rare in alimentary tract and many
      other organs. This case may be value to delineate the nature of this disease.

PMID- 9146066
TI  - [Motor paresis with cheiro-oral topography due to small infarct in the internal
      capsule or the corona radiata].
AB  - We reported five patients having presented only with clumsy hand and dysarthria
      which resulted from motor paresis confined to one side of the fingers and the
      ipsilateral face and tongue. All of them were right-handed, and their
      manifestation was transient. They had no abnormalities of muscle tonus and
      sensation, and no ataxia. The features of these cases differed from those of the
      dysarthria-clumsy hand syndrome because of absence of ataxia, and could be
      distinguished from pure motor hemiplegia by a motor paresis with cheiro-oral
      topography. MRI examinations showed a localized lesion at the border between
      internal capsule and corona radiata (two cases), or in the corona radiata just
      over this region (three cases). In the former cases in which the internal capsule
      was involved, we confirmed the lesion in the genu and anterior half of the
      posterior limb of the internal capsule. The lesion was on the left side in all
      five patients. It has been known that the pyramidal tract consists of the large
      and small fibers. The large ones are localized in the posterior part of the
      posterior limb of the internal capsule, and the damage of them produces sustained
      and serious motor paralysis. The small ones are widely distributed in the genu
      and the posterior limb of the internal capsule. The findings of our study suggest
      that the small fibers have adjacent somatotopy for the hand and mouth in the
      region of the genu and the anterior part of the posterior limb of the internal
      capsule, and that the damage of them may lead to mild, transient motor paresis
      without spasticity.

PMID- 9146067
TI  - [In-111-labeled leukocyte brain SPECT imaging in acute ischemic stroke in man].
AB  - This study was performed to investigate the role of leukocyte accumulation in
      human cerebral infarction and its association with neurological functional
      outcome. A total of 42 patients diagnosed as acute ischemic stroke (22 embolism,
      17 thrombosis, 3 TIA) were examined. Leukocyte accumulation was studied using
      indium-111-labeled leukocyte brain single-photon emission computed tomography
      (SPECT). Volume of brain infarction was evaluated by CT and/or MRI. The data were
      compared with the cerebral blood flow (CBF) imaging. Immediately after CBF study
      by SPECT using either technetium-99m hexamethylpropyleneamine oxine (Tc-99m
      HMPAO) or technetium-99m ethyl-cysteinate dimer (ECD), In-111-labeled autologous
      leukocytes were injected intravenously. Brain scan for leukocytes was performed
      after 48 hours. The European Stroke Scale was used for neurological assessment.
      Thirteen patients with cerebral embolism and three patients with cerebral
      thrombosis showed intensive accumulation of leukocytes in the region of low flow.
      Leukocyte's accumulation was not seen in patients with TIA. The accumulation of
      leukocytes was more noticeable in the central zone of the ischemia. Patients who
      showed negative leukocyte accumulation revealed clinically mild functional
      outcome and the size of infarction on CT and/or MRI was small. The regional
      accumulation of leukocytes was seen in all the patients with hemorrhagic
      infarction, but the degree of hemorrhage on CT did not have significant influence
      on the amount of leukocyte accumulation. Abnormal accumulation of leukocytes was
      associated with reduced CBF during the acute embolic stroke. The present clinical
      study revealed that leukocyte accumulation correlated with the poor neurological
      functional outcome in patients with acute embolic stroke. The present study
      confirms that leukocytes contribute to the ischemic tissue damage of the brain
      and demonstrates a clinical evidence that the regional accumulation of leukocytes
      has a deleterious effect on the brain following ischemia.

PMID- 9146068
TI  - [Accuracy of three-step diagnosis in discriminating subtypes of acute ischemic
      stroke].
AB  - The aim of this study is to evaluate the accuracy of three-step diagnosis in
      discriminating subtypes of acute ischemic stroke. A total of 120 consecutive
      patients with first-ever ischemic stroke, admitted to one general hospital, were
      prospectively studied. In the first step (within 24 hours of clinical onset), the
      first diagnosis was made according to clinical symptoms and signs, and patients
      were subdivided into four groups according to the classification of Oxfordshire
      Community Stroke Project: lacunar infarcts (LACI), total anterior circulation
      infarcts (TACI), partial anterior circulation infarcts (PACI), and posterior
      circulation infarcts (POCI). In the second step (24 hours to 72 hours from the
      onset), neuroimaging diagnosis was performed by CT and/or MRI. Four lesion sites
      were classified: 1) small subcortical infarction < or = 1.5 cm in diameter in the
      perforating artery territory (SSI), 2) supratentorial cortical or striatocapsular
      infarction (CI), 3) low-flow infarction (LFI) which includes centrum semiovale
      infarct and internal junctional infarct, and 4) posterior circulation infarction
      other than SSI (PI). In the third step, etiological diagnosis was made by
      examination including trans-thoracic echocardiography and MRA (3-D, PC). In
      accordance with the TOAST Study, the presumed stroke mechanism was categorized as
      either small-vessel occlusion (lacune), cardioembolism (CE), large-artery
      atherosclerosis (LAA), or others. The majority of patients with TACI, PACI or
      POCI showed the corresponding lesions on CT or MRI, while only 69% of LACI
      patients demonstrated SSI. Seventy-five percent of patients with TACI were
      categorized as CE in the third diagnosis, while the etiology of the patients with
      PACI was either CE or LAA in equal numbers. Only 60% of LACI patients were
      classified as lacune and 21% of them as LAA. Patients with LACI but classified as
      LAA usually had atypical clinical symptoms (e.g. monoparesis) and lesions other
      than SSI. The positive predictive value (PPV) of lacune in the combination of
      LACI and SSI was 0.75. Eighty-two percent of patients with CE had atrial
      fibrillation (af), which was the most frequent cardioembolic source. When
      patients with TACI or PACI had af, the PPV of CE was 0.93, but when they did not,
      the PPV of LAA was only 0.68. The etiology of POCI was variable. In conclusion,
      the agreement of the three-step diagnosis is considerable, but more rigorous
      clinical examination is needed for some clinical groups (POCI and LACI) and the
      etiological diagnosis of LAA.

PMID- 9146069
TI  - [A case of myeloradiculoneuropathy associated with persistent high titers of anti
      GM1 and anti-GD1b antibodies].
AB  - A 60-year-old woman was admitted to our hospital with bilateral weakness of the
      lower limbs. She had been suffering from spastic paraparesis of unknown origin
      for 12 years since she was 48. Myelopathy with the Th6 level appeared when she
      was 52 and underwent gradual deterioration. On admission, she showed spastic
      paraparesis and myelopathy with the Th6 level. A thoracic spinal MRI examination
      revealed a wholly thin spinal cord. EMG demonstrated that the conduction velocity
      of the peroneal nerve was 37.8m/sec, and F waves were not evoked on stimulation
      of the peroneal nerve. Although the anti-GM1 and anti-GD1b antibody titers in the
      serum were increased on admission, their values decreased transiently after whole
      plasmapheresis. There was accompanying impairment of the radiculoneuropathy and
      myelopathy. It is important to measure the titers of anti-ganglioside antibodies
      in patients with myeloradiculoneuropathy of unknown origin, and whole
      plasmapheresis is considered to represent a useful treatment for this type of
      illness.

PMID- 9146070
TI  - ["Associative" visual agnosia for objects, pictures, faces and letters with
      altitudinal hemianopia].
AB  - We report a 63-year-old right-handed man with the associative visual agnosia and
      bilateral altitudinal hemianopia. Neurological examination revealed fair visual
      acuity and normal ocular movement. Other cranial-nerve, motor, sensory, and
      autonomic functions were normal. The brain MRI showed multiple infarction
      involving the right fusiform and lingual gyri extending to the adjacent white
      matter of the occipito-temporal lobes and posterior part of the parahippocampus,
      the left fusiform and lingual gyri, and multiple lacunae in bilateral basal
      ganglia. Cerebral angiography demonstrated occlusion at the P1 portions of
      bilateral posterior cerebral arteries. 123I IMP-SPECT revealed decreased
      perfusion in bilateral occipital lobes, worse on the right. Visual evoked fields
      showed normal pattern of P100 m on bilateral occipital lobes.
      Neuropsychologically he was alert and oriented in place. In WAIS-R, he could not
      perform any of performance subtests, while his VIQ was 72. His verbal and visual
      memory was impaired. His visual perception of forms seemed to be almost
      preserved. He could copy simple drawing precisely, although he could not
      recognize the drawing just copied. He could match pictures, letters and
      photographs of faces. His visual identification of forms, on the other hand, was
      severely disturbed. He could identify only simple geometrical figures, but not
      simple drawings such as an apple or the face of his daughter. Reading Kanji was
      impaired and he read Kana in letter-by-letter manner. Tactile identification of
      objects was much better than visual one. Naming objects from verbal description
      was well preserved. Drawing fruits or cars from memory was intact. These data
      suggests that the present case had fairly good visual perception as was
      demonstrated by good copying and matching performance, and the case could be
      classified into the associative type of visual agnosia if the dichotomized
      classification of apperceptive and associative type is employed. However, closer
      look at his way of copying clearly showed that he copied in piecemeal fashion,
      suggesting difficulty in seeing a figure as a dynamic whole. It is possible that
      fine and precise discrimination of shape and pattern is subserved by the
      bilateral ventral or occipito-temporal visual system which was compromized in the
      present case.

PMID- 9146071
TI  - [Dystonic movement of the left upper limb in a case of the right pontine
      hemorrhage].
AB  - We report a 69-year-old woman who presented with dystonic movement in the left
      upper limb. She also had left hemiparesis and sensory disturbance in the right
      face and the left half of the body, pseudoathetosis in the left hand, and
      hotness, swelling, and lead-pipe rigidity in the left upper limb. The dystonic
      movement was presented mainly in the proximal part of the left upper limb, and
      was induced by voluntary movements; for example, when she was ordered to shake
      hands, the left shoulder always abducted with the flexion of the left elbow.
      Brain MRI showed a fresh hemorrhage in the dorsal part of the right middle pons
      including the base and the tegmentum, old infarctions in the right postero
      lateral thalamus, putamen, and right parietal lobe. The dystonic movement
      persisted for 2 weeks, and hotness and swelling in the left upper limb lasted for
      2 months, while the rigidity and pseudoathetosis persisted for 7 months or more
      despite medication.

PMID- 9146072
TI  - [A case of Guillain-Barre syndrome after the travel in southeast Asia--isolation
      of Campylobacter jejuni PEN 5 serotype].
AB  - A 57-year-old man, while on travel in Malaysia, suffered from diarrhea after he
      ate fruits. He developed limbs weakness without sensory disturbance after his
      return to Japan. Serum from the patient had high IgG anti-GM1 antibody titer.
      Campylobacter jejuni was isolated from his stool. The serotype belonged to PEN 5.
      The patient received double-filtration plasmapheresis 7 times during from days 6
      to 17. Muscle strength began to recover gradually on day 10, and returned to
      normal 5 months after the onset of neurologic symptoms. Repeated neurophysiologic
      studies indicated that the axonal degeneration of motor nerves was predominant
      process. This case suggests that Guillain-Barre syndrome is a complication of
      traveler's diarrhea.

PMID- 9146073
TI  - [Small hand muscle atrophy as an initial sign in HTLV-I associated myelopathy].
AB  - A 68-year-old female had been well until the age of 52 when she noticed weakness
      and atrophy of her right small hand muscles. She began to have gait disturbance
      at the age of 63. On admission, neurological examinations revealed atrophy and
      weakness of the small hand muscles on both sides as well as spastic paraparesis.
      As the antibody titer for human T-lymphotropic virus type I (HTLV-I) was elevated
      both in the serum and CSF, a diagnosis of HTLV-I associated myelopathy (HAM) was
      made. Electrophysiological studies showed neurogenic changes and suggested
      anterior horn cell involvement. After oral administration of prednisolone, her
      spasticity and gait disturbance improved slightly. Small hand muscle atrophy can
      be one of the initial signs of HAM, and may mimic amyotrophic lateral sclerosis
      and cervical spondylosis.

PMID- 9146074
TI  - [Familial parkinsonism: different clinical phenotype between a mother and her
      daughter].
AB  - We reported a familial case of parkinsonism in which clinical features are
      different between a mother and her daughter. The mother developed rigidity and
      bradykinesia at age 76. Her symptoms were slowly progressive, and were responsive
      to levodopa. Thus, she was diagnosed as having Parkinson's disease. In contrast,
      her daughter developed postural instability as well as rigidity and bradykinesia
      at age 53 in rapid progression. In addition, she also developed pyramidal signs
      and autonomic failures, including orthostatic hypotension and urinary
      incontinence. The disease phenotype of the daughter resembled that of
      striatonigral degeneration (SND). However, PET studies showed normal binding of
      11C-N-methyl-spiperone (NMSP) in the striatum, suggesting that the daughter was
      also affected with Parkinson's disease.

PMID- 9146075
TI  - [Heterogeneity in breakpoint location of duplication in Japanese Charcot-Marie
      Tooth disease type 1A].
AB  - The crossover breakpoints for CMT1A are located in the CMT1A-REP repeat flanking
      a 1.5 Mb region of chromosome 17p11.2-12. We analysed the relationship between
      the breakpoint locations and clinical phenotypes in 21 Japanese patients with
      CMT1A duplication. The CMT1A-REP region was divided in 5 regions, A, B, C, D and
      E, based on restriction site differences between the proximal and distal CMT1A
      REP repeats (Kiyosawa et al., HMG, 1995). The breakpoint location within the
      CMT1A-REP was heterogeneous, the frequency distribution of which was hightest in
      the B/C region and similar to that in Caucasian patients. The clinical
      phenotypes, such as foot deformity, muscular weakness and atrophy, sensory
      impairment and electrophysiologic finding, were extensively variable among the
      CMT1A patients with PMP22 gene duplication. The location of breakpoints was not
      related to the clinical phenotypes, suggesting that there is a factor other than
      the location of the crossover breakpoint, which influences phenotypic
      manifestation of CMT1A.

PMID- 9146076
TI  - [Parkinsonism in a patient receiving interferon alpha therapy for chronic
      hepatitis C].
AB  - We report a case of Parkinsonism due to interferon alpha (IFN alpha) therapy for
      chronic hepatitis C. A 51-year-old female received IFN alpha (Sumipheron@6 x
      10(6) IU), three times a week by intramuscular injection. Six months after the
      initiation of IFN alpha therapy, she noticed tremor of bilateral fingers, and was
      admitted to our hospital. Neurological examination revealed muscle rigidity,
      bilateral finger tremor, mild bradykinesia. Tremor was more extreme at posture
      rather than at rest. She was diagnosed as Parkinsonism, and carbidopa-levodopa
      therapy was effective. Attention must be paid to Parkinsonism, when IFN alpha is
      administered.

PMID- 9146077
TI  - [A case of Sjogren's syndrome with a high titer of anticardiolipin antibody that
      developed as parkinsonism].
AB  - A 50-year-old-male consulted us, complaining of gait disturbance. He was
      diagnosed as having Parkinson syndrome, but had no benefit of drugs for Parkinson
      disease. On admission he showed symptoms of parkinsonism such as parkinsonian
      gait, bradykinesia and muscle rigidity, and recurrent aseptic meningitis.
      Additionally, his condition was complicated by Sjogren's syndrome, based on the
      preliminary criteria of Sjogren's syndrome established by the European Community.
      Because his parkinsonism and meningitis were considered to be caused by Sjogren's
      syndrome, he was administered corticosteroids, which improved his parkinsonism
      and aseptic meningitis. The brain MR images in our case did not match those
      typically reported in cases of central nervous system Sjogren's syndrome (CNS
      SS). Although the most common abnormalities are small distinct areas of increased
      signal intensity on T2-weighted images, the MR images in our case revealed
      periventricular diffuse areas of increased signal intensity on T2-weighted
      images. Although his parkinsonism and aseptic meningitis are believed to the
      effects of vasculitis caused by Sjogren's syndrome, it is also possible that his
      parkinsonism is related to Binswanger's disease resulting from a high titer of
      anticardiolipin antibody. Our report proposes a possible relationship between
      anticardiolipin antibody and CNS-SS when MR images reveal diffuse high intensity
      areas on T2-weighted images.

PMID- 9146078
TI  - [Delayed exacerbation of cervical myelopathy in a case of juvenile muscular
      atrophy of unilateral distal upper extremity].
AB  - We reported a case in which cervical myelopathy exacerbated 20 years after the
      stabilization of juvenile muscular atrophy of unilateral distal upper extremity.
      The patient presented progressive weakness in the right proximal upper extremity
      and spastic paraparesis in addition to the long-lasting muscular atrophy of right
      distal upper extremity. Plain x-ray showed severe cervical spondylosis with
      kyphosis of the cervical spine. Dynamic study on MRI disclosed cervical spinal
      cord atrophy and compression enhanced in both flexion and extension position of
      the neck. Malalignment (kyphosis) and severe spondylotic change of the cervical
      spine seemed to affect the spinal cord with little functional reservoir,
      manifesting the delayed exacerbation of myelopathy. We conclude that malalignment
      and subsequent spondylotic change of the cervical spine would be significant
      factors to determine the long term prognosis of patients with juvenile muscular
      atrophy of unilateral distal upper extremity.

PMID- 9146079
TI  - [A reversible posterior leukoencephalopathy syndrome in a patient with classical
      polyarteritis nodosa].
AB  - We report a case of a reversible posterior leukoencephalopathy syndrome (RPLS). A
      57-year-old male had classical polyarteritis nodosa with mononeuritis multiplex,
      renal insufficiency, and a high titer of p-ANCA (MPO). He was normotensive. He
      was treated with high dose methylprednisolone and then with oral prednisolone and
      cyclophosphamide. Despite the treatment, his renal function rapidly deteriorated
      and hypertension progressed. He had two generalized seizures; at that time his
      blood pressure was 200/140 mmHg. CT scan revealed bilaterally symmetric
      hypodensities in the thalamus, the occipital white matter, and the brainstem. T2
      weighted MRI showed increased signal intensities in the temporo-occipital white
      matter, the thalamus, the posterior limbs of the internal capsules, the external
      capsules, the midbrain, the pons, and the middle cerebellar peduncles. T1
      weighted images showed hypointensities in these areas. Treatment with nifedipine
      improved his blood pressure; 5 days later he was only moderately disoriented.
      Follow-up CT demonstrated an ill-defined hypodense area only in the left parietal
      lobe. To our knowledge, there are only two reported cases of RPLS associated with
      systemic vasculitides. Interestingly, thalamic lesions are outstanding also in
      these cases. Under these circumstances, treatment of hypertension is of primary
      importance, and steroid therapy should not be withdrawn or reduced.

PMID- 9146080
TI  - [Kinesigenic supplementary motor seizure? A case report].
AB  - Supplementary motor seizure (SMS) and paroxysmal kinesigenic choreoathetosis
      (PKC) appear similar, but are generally considered to represent different disease
      entities. We report a case that shared the clinical features of both disorders. A
      62-year-old woman presented with attacks consisting of brief tonic posturing of
      four limbs, more prominent on the right side. The attack started at age 59 and
      subsequently began to occur about 20 times daily. Her consciousness was preserved
      during the attack. The attack lasted 5-15 sec. The attacks were often evoked by
      sudden initiation of movement, but also occurred spontaneously and even during
      sleep. She had never experienced generalized convulsion. Ictal scalp EEG showed
      high amplitude beta activity appearing a few seconds before the attacks around
      the vertex. Otherwise EEG was within normal limits. The response to anti
      convulsant medication was poor and a combination of three kinds of drugs was
      needed. An almost identical case was reported as "PKC" by Lombroso. His case
      showed unequivocal epileptiform discharges arising from the supplementary motor
      area. Accordingly, our case is considered kinesigenic SMS. It seems important to
      examine similar cases to elucidate the relationship between SMS and PKC, or
      between the kinesigenic and non-kinesigenic types of these disease entities.

PMID- 9146081
TI  - [A case of diffuse fasciitis and its MRI findings].

PMID- 9146082
TI  - Obesity in Texas.

PMID- 9146083
TI  - Medicaid train wreck.

PMID- 9146084
TI  - Bogged down.

PMID- 9146086
TI  - Diet, health and history. Diet's role in disease is food for thought.

PMID- 9146085
TI  - UT's HMO.

PMID- 9146087
TI  - Conflicts of interest.

PMID- 9146088
TI  - Diagnosis and treatment of perilunate dislocations.

PMID- 9146089
TI  - Hepatic hemangioma: a review.
AB  - Hemangioma is a common hepatic lesion. The incidence is reported to be around 2%.
      The etiology of these lesions is unclear. Hemangioma should be regarded as benign
      with distinct clinicopathological features. Although most patients are
      asymptomatic, some may present with abdominal mass, cardiac failure,
      coagulopathy, or rupture. Hemangioma presents a diagnostic challenge. The surgeon
      should be aware of this lesion to avoid the pitfalls in differential diagnosis. A
      misinterpretation of hypervascular metastasis may lead to marked mismanagement.
      We emphasize the necessity of relatively specific and sensitive investigations in
      the differential diagnosis of a liver nodule. Surgery alone is usually
      unnecessary. Therapeutic options include steroids, hepatic artery ligation,
      therapeutic embolizations, radiation therapy, and chemotherapy. Available data
      suggest a favorable prognosis.

PMID- 9146090
TI  - Shortening duration of treatment of multibacillary leprosy.

PMID- 9146091
TI  - Expanded programme on immunization (EPI). Diphtheria control.

PMID- 9146092
TI  - Learning disabilities occurring concomitantly with other disability and
      exceptional conditions: introduction to the special series.

PMID- 9146093
TI  - The concomitance of learning disabilities and emotional/behavioral disorders: a
      conceptual model.
AB  - Although research has documented overlapping and coexisting characteristics of
      learning disabilities and emotional/behavioral disorders, little attention has
      been paid to the subset of students who manifest symptoms of both disorders
      (LD/EBD). This gap in our professional knowledge/research base may be due to (a)
      exclusive language in federal definitions that promotes differentiation of
      disabilities rather than recognition of symptom overlap; (b) the lack of a
      conceptual model of concomitant learning and emotional/behavioral disorders; and
      (c) the absence of a research focus on this population. In this article, we
      construct a conceptual model involving six critical domains of relevance to
      students with LD/EBD. After describing the utility of this interactive and
      functional model, we highlight critical issues in screening, assessment, and
      programming for children with concomitant LD/EBD.

PMID- 9146094
TI  - Learning disabilities existing concomitantly with communication disorder.
AB  - This article describes the characteristics of language disorders that occur with
      learning disabilities. In this context, formal and naturalistic language,
      including specific standardized test batteries and curriculum-based language
      assessment, portfolio assessment, and others, are discussed. In addition, service
      delivery models and interventions that focus on the enhancement of semantic,
      syntactic, and pragmatic development are presented. Finally, future directions
      for research in the area of learning disabilities and secondary language
      disorders are suggested. Intervention strategies, including supportive
      scaffolding, whole language, and collaborative consultation, are reviewed; and
      implications for language assessment, intervention, and future research are
      discussed.

PMID- 9146095
TI  - Gifted children with learning disabilities: a review of the issues.
AB  - Many people have difficulty comprehending that a child can be gifted and also
      have learning disabilities. As a result, children with special needs that result
      from both their high abilities and their learning problems are rarely identified
      and are often poorly served. This article explores the current policies and
      practices with regard to defining, identifying, and educating this population.
      Recommendations are included that would help ensure that students who are gifted
      and have learning disabilities receive the intervention needed to help them
      achieve their full potential.

PMID- 9146096
TI  - Mental retardation and learning disabilities: conceptual and applied issues.
AB  - The relationship between mental retardation and learning disabilities is clouded
      by conceptual issues and current practices in applied (i.e., educational and
      noneducational) settings. In this article, we initially discuss whether mental
      retardation can be considered a concomitant disability associated with learning
      disabilities or whether these two disabilities are mutually exclusive categories.
      Conceptual issues related to this question are then reviewed to provide a
      perspective for viewing these two traditional areas of exceptionality. Emerging
      areas of concern in term of definition, classification, etiology, and lifelong
      issues are addressed. Attention is then given to applied issues that have a
      direct effect on the lives of individuals with disabilities. Specific topics
      include educational curricula, instruction, inclusion, and adult services and
      supports.

PMID- 9146097
TI  - The student with a visual disability and a learning disability.
AB  - Existing studies indicate that between 14% and 65% of students with visual
      disabilities also have learning disabilities. The similar symptoms of the two
      conditions and the earlier identification of a visual disability often mask the
      presence of a learning disability. This article addresses definition, assessment,
      intervention, and future implications related to educational practices with
      students who have both learning and visual disabilities. The definitions of the
      two conditions are compared, emphasizing features that make identification
      difficult. The article examines common assessment procedures, describing
      approaches that are inappropriate for students who have low vision or blindness.
      Intervention approaches are described, including adaptations of the environment,
      enhancement of vision, instruction in compensatory skills, the use of learning
      strategies, and the availability of learning opportunities. Future directions
      include refinement of diagnostic approaches, and research related to the
      characteristics and instructional needs of students who have both visual and
      learning disabilities.

PMID- 9146098
TI  - Learning disabilities occurring concomitantly with linguistic differences.
AB  - This article discusses characteristics of educational environments that
      facilitate success for culturally and linguistically diverse (CLD) learners,
      thereby reducing inappropriate referrals to special education, and offers
      recommendations for adapting referral and assessment processes to better serve
      CLD students suspected of having learning disabilities. Effective instructional
      practices are considered, and competencies needed by teachers who serve CLD
      students with learning disabilities are suggested. Specific attention is given to
      identifying and serving students with learning disabilities who are also limited
      English proficient.

PMID- 9146099
TI  - Comparing efficacies of neurocognitive treatment and homework assistance programs
      for children with learning difficulties.
AB  - The purpose of the study was to analyze the relative efficacies of two treatments
      for children with learning difficulties. The first treatment consisted of
      multiple training components targeting specific cognitive and behavioral factors;
      the second treatment provided emotional support and supervision of school tasks.
      The participants were 94 Chilean schoolchildren (6 to 11 years of age). The
      efficacies were compared on (a) neurocognitive tests, (b) school achievement
      tests, and (c) behavior in school and at home. The results indicated that both
      groups improved on most of the outcome measures. The first group showed best
      results in parents' rating of home behavior, and the second group in reading. The
      findings also emphasized the importance of emotional support and the inclusion of
      a parents' group in treatment for children with learning difficulties.

PMID- 9146100
TI  - Differences between learning disability subtypes classified using the revised
      Woodcock-Johnson Psycho-Educational Battery.
AB  - This study examined the characteristics of students with specific learning
      disabilities in either reading and spelling or arithmetic. Based on scores
      obtained using the revised Woodcock-Johnson Psycho-Educational Battery, students
      with a marked weakness in arithmetic relative to reading and spelling were
      designated as Group A. Group R-S showed the opposite pattern. Each group included
      30 participants ranging in age from 7 to 16 years, with a mean age of 10 years.
      The boy-to-girl ratios were 16:14 and 19:11 in Group A and Group R-S,
      respectively. Comparisons using measures from the Wechsler Intelligence Scale for
      Children-Third Edition (WISC-III) indicated that Group A was weaker in nonverbal
      skills than Group R-S, despite equivalent overall IQ scores between the two
      groups. Group R-S showed a within-group strength in nonverbal versus verbal
      skills. Group A students were more likely than Group R-S students to have
      counseling provided as part of their Individualized Education Program, suggesting
      greater socioemotional difficulty among Group A students. The present study
      supports the connection between nonverbal skills and socioemotional functioning
      noted by previous researchers, and generalizes findings from earlier studies to
      more current test editions.

PMID- 9146102
TI  - Explaining "pain and suffering" awards: the role of injury characteristics and
      fault attributions.
AB  - The present research explored factors thought to affect compensatory awards for
      non-economic harm ("pain and suffering") in personal injury cases. Experiment 1
      showed that the nature and severity of the plaintiff's injury had a strong effect
      on perceptions of the extent of harm suffered and on award amounts. The parties'
      relatively active or passive roles in causing the injury affected assessments of
      their degree of fault, but perceived fault had little influence on awards.
      Experiment 2 replicated with more varied cases the strong impact of injury
      severity on harm perception and on awards for pain and suffering. In both
      studies, the disability and the mental suffering associated with injuries were
      stronger predictors of awards than were pain and disfigurement.

PMID- 9146101
TI  - The MacArthur adjudicative competence study: development and validation of a
      research instrument.
AB  - Assessment of competence to stand trial is a common evaluation that can have
      substantial consequences for defendants and the criminal justice system. Despite
      a voluminous literature, much remains unknown. An obstacle to progress in
      understanding what is better termed "adjudicative competence" is the absence of
      structured, standardized research measures for assessment of defendants. This
      article presents the legal framework, assessment strategy, instrument
      description, psychometric properties, and construct validation of the MacArthur
      Structured Assessment of the Competencies of Criminal Defendants (MacSAC-CD). The
      measures meet or exceed accepted indices of internal consistency, and interscorer
      agreement. Observed patterns of correlations among measures support the
      underlying theoretical structure of competence-related abilities. Moreover, the
      MacSAC-CD distinguishes groups of competent and incompetent defendants; reflects
      changes in competence status; and correlates positively with clinical judgments,
      negatively with psychopathology and impaired cognitive functioning, and
      negligibly with cynicism toward the justice system.

PMID- 9146103
TI  - Cross-validation and extension of the violence risk appraisal guide for child
      molesters and rapists.
AB  - A cross-validation of the Violence Risk Appraisal Guide was performed on a sample
      of 159 child molesters and rapists followed for an average of 10 years at risk.
      The performance of the instrument was also examined on a 10-yr followup of 288
      sex offenders that included both those in the original construction sample for
      the VRAG and the validation sample. The instrument performed as well as it had in
      construction for predicting violent recidivism in both the cross-validation and
      extended followup samples, and moderately well in the prediction of sexual
      recidivism. Survival analyses showed that child molesters exhibited higher risk
      of sexual recidivism than rapists or offenders against both children and adults,
      whereas the opposite was true for violent recidivism. As predicted, psychopathy
      and phallometrically determined sexual deviance exhibited a multiplicative
      interaction effect on sexual recidivism. Proportional hazards event history
      analyses supported the use of the VRAG for the prediction of violent recidivism
      among sex offenders.

PMID- 9146104
TI  - Consultant practice in occupational health. AAOHN advisory.

PMID- 9146105
TI  - Successful business process design. Business plan development for the
      occupational health services unit.
AB  - 1. The occupational health nurse is often mandated by management to validate
      health services offered and programs developed for employees as valuable to the
      business and company mission. 2. The business plan of the occupational health
      service is a working document, changing as needs of the client/customer and
      internal and external business and socio-economic environment evolve. 3.
      Alignment with and support of the company mission, goals, and objectives is
      another method of proving good occupational health is good business. 4. Business
      planning is a basic business tool the wise and prudent occupational health nurse
      can use in proving good occupational health is vital to the success of a company.

PMID- 9146106
TI  - Potential emotional and cognitive disorders associated with exposure to EMFs. A
      review.
AB  - 1. Published studies have found neither a consistent association nor a simple
      dose-response relationship between exposure to EMFs and emotional and cognitive
      responses. 2. The inconsistency in results and lack of a simple dose-response
      relationship suggest that the potential association between EMFs and cognitive
      and emotional responses is complex, possibly restricted to specific exposure
      frequencies and intensities and confounded by exposure to other stressors. 3.
      Further work to examine the association between EMFs and cognitive and emotional
      responses by specific electromagnetic frequencies and intensities in the context
      of known sources of stress is indicated.

PMID- 9146107
TI  - Student/faculty practice and research in occupational health. Health promotion
      and outcome evaluation.
AB  - Faculty strive to connect theory and practice with real life situations for
      students. This study evolved from student intervention with small industries as
      part of their undergraduate community health nursing clinical experience. A pre
      experimental static group design was used to explore the impact of health service
      availability on selected cardiovascular risk factors. Levels of health service:
      a) no service; b) student service; and c) formal health care service were
      compared. Chi-square, t-tests and MANOVA analyses supported three hypotheses that
      student intervention was equally as successful as formal health care service in
      reducing the selected cardiovascular risk factors of high weight to height
      ratios, blood pressure readings above 140/90 on three separate measurements,
      total cholesterol readings above accepted norms, and a health risk profile that
      identifies risk for cardiovascular disease.

PMID- 9146108
TI  - Evaluation of a 3 year education and training program. For nursing personnel at a
      Swedish hospital.
AB  - An education and training program comprising 1) patient transfer technique, 2)
      physical fitness exercise, and 3) stress management was conducted during 3
      consecutive years at a Swedish hospital. The present study was based on data from
      four sets of questionnaires, distributed to 348 female nursing personnel who
      participated in the entire program. The aim of the study was to evaluate the
      program. It was evident from the questionnaires that 90% of the subjects were
      positive about participating in the program and 88% expected that participation
      would lead to decreased musculoskeletal disorders. However, no decrease in the
      prevalence of musculoskeletal symptoms during the study time period was observed.
      One year after the cessation of the program, 93% of all nurses reported they
      mostly or always used the new patient transfer technique and 99% considered it to
      be useful.

PMID- 9146109
TI  - Diabetes update.

PMID- 9146110
TI  - Business skills for occupational health nurses: preparing the perfect resume.

PMID- 9146111
TI  - Medication management in the workplace.

PMID- 9146112
TI  - Employee perceived stress. Relationship to the development of repetitive strain
      injury symptoms.
AB  - Repetitive strain injuries (RSIs), specifically carpal tunnel syndrome, are the
      fastest growing type of occupational injury. Research about precipitating factors
      and prevention has been controversial and inconclusive. Preventive measures
      typically have addressed ergonomic changes. The purpose of this research article
      is to describe the effects of several variables on the perceived development of
      RSI symptoms, particularly those of carpal tunnel syndrome. Emphasis was placed
      on the role of perceived stress. The study design was a descriptive survey using
      a nonprobability sampling method. The study focused on four variables related to
      perceptions of symptoms: 1) perceptions of level of knowledge related to the
      prevention of RSIs; 2) taking a specific action to make one's workstation more
      ergonomically correct; 3) perceptions of having ergonomically correct
      workstations; and 4) perceptions of being stressed. Study results indicated that
      perceived stress was significantly associated with perceived RSI symptoms.
      Workers who use a computer 4 or more hours per day reported significantly more
      symptoms than those who did not. At risk computer users who perceive an
      ergonomically correct workstation reported fewer symptoms. To prevent RSIs,
      occupational health nurses must address ergonomics, stress levels, and knowledge
      levels.

PMID- 9146113
TI  - Unknown toxic exposures. Arts and crafts materials.
AB  - 1. Arts and crafts material containing toxic chemicals have been found to be
      hazardous to human health. 2. Artists/craftspersons, who also may be employed in
      industry, often are unaware or not adequately informed about the toxic nature of
      many art products. 3. The occupational health nurse is in a critical position to
      identify and monitor the worker exposed to toxic chemicals both in the workplace
      and at home/art studio. 4. Education about hazardous substances can prevent
      illness or injury. With expertise in public health, occupational health nurses
      are in a key position to provide community education about the dangers of toxic
      art materials to the general public and the health care community.

PMID- 9146114
TI  - Expertise partnering--occupational health services and EAPs. Successful program.
AB  - 1. Positive partnering is another way of working together to develop a business
      plan providing quality assured, cost effective health care programs. 2. In a
      professional atmosphere of trust and mutual respect, creative programs develop
      naturally. 3. Professional interdisciplinary partnering can lead to more cost
      effective, quality assured health care delivery.

PMID- 9146115
TI  - Assessment of the trauma victim in an occupational setting.
AB  - 1. It is important for the occupational health nurse to be aware of and
      understand the mechanism of injury and forces involved in a trauma event. This
      understanding provides insight into the potential injuries that may be present
      even if the victim appears unhurt. 2. The primary survey is designed to rapidly
      determine life threatening problems and provide immediate interventions. 3. The
      secondary survey is a more detailed, head to toe assessment of the victim to
      determine if other injuries are present. This part of the examination helps
      determine more subtle findings.

PMID- 9146116
TI  - Health effects of stress management in the worksite.

PMID- 9146117
TI  - The Internet: occupational health nurse's approach the information superhighway's
      on-ramp.

PMID- 9146118
TI  - Mentoring the mentoree is not a one-way street.

PMID- 9146119
TI  - Qualitative research in nephrology nursing.
AB  - Qualitative research is being used to a great extent in nursing. It offers nurses
      the opportunity to obtain rich understandings of phenomena of interest. The term,
      qualitative research, is used to describe a broad range of research
      methodologies. Each methodology has an underlying set of values, beliefs, and
      assumptions and offers a particular lens to further understanding the area of
      interest. Common forms of qualitative research, specifically, ethnography,
      grounded theory, feminist research, action research, historical research, and
      qualitative evaluation research are briefly described and examples from the
      nephrology nursing research literature are provided when available. Methods for
      critiquing and reviewing qualitative research are suggested.

PMID- 9146122
TI  - Discipline and children with chronic illnesses: strategies to promote positive
      patient outcomes.
AB  - Children with end stage renal disease (ESRD) often present psychosocial problems
      that include noncompliance to treatment. Caregivers can, by understanding the
      various models of discipline, select proactive and reactive strategies to
      encourage cooperation. These strategies are grounded in discipline models that
      include biophysical, behavioral, humanistic, psychodynamic, ecological,
      psychoeducational, and cognitive models. This article describes various
      discipline procedures for children with chronic illness. It emphasizes discipline
      with dignity while empowering and involving children in their behavior
      management.

PMID- 9146120
TI  - Ethical conflicts reported by Certified Nephrology Nurses (CNNs) practicing in
      dialysis settings.
AB  - OBJECTIVE: The purpose of the investigators was to describe and classify ethical
      conflicts experienced by Certified Nephrology Nurses (CNNs) practicing in
      dialysis settings in four eastern states and the District of Columbia, and to
      explore associated demographic, educational, and practice setting factors
      associated with these ethical conflicts. DESIGN: A descriptive survey design was
      used. SAMPLE/SETTING: All members of the American Nephrology Nurses Association
      (ANNA) who were CNNs working in Maryland, Virginia, and the District of Columbia,
      and a random sample of those in New York State and Pennsylvania were contacted.
      METHODS: Those CNNs working in dialysis settings were asked to complete the
      Demographic Data Form and the Moral Conflict Questionnaire developed by Fry
      (1990). Eighty-eight met inclusion criteria, agreed to participate, and described
      ethical conflicts. RESULTS: By far the most common practice context for the
      described ethical conflicts were decisions about discontinuation or initiation of
      dialysis (69%). Participants were clear about the moral problem and ethical
      principles involved. CONCLUSIONS: Participants reported being involved in serious
      ethical conflicts about patient care. Since two-thirds were not resolved, further
      research should investigate whether existing mechanisms in practice settings for
      resolution of ethical conflicts are not working or are not being used by nurses.

PMID- 9146123
TI  - Autosomal dominant polycystic kidney disease: pathophysiology and treatment.
AB  - Once viewed as a hopelessly incurable disease, autosomal dominant polycystic
      kidney disease (ADPKD) has been given a great deal of attention as geneticists
      search for ADPKD genes, and cell biologists are studying and understanding cyst
      formation. Alterations in cellular growth, secretion, and extracellular matrix
      all participate in cystogenesis. ADPKD is one of the most common hereditary
      diseases in the United States and is a frequent cause of chronic renal failure.
      The disease is a systemic disorder that may affect multiple organ systems.
      Manifestations of ADPKD in renal and extrarenal systems may be challenging
      problems in the management of these patients. Although no therapy is available,
      treatment of the complications is highly effective in most cases in supportive
      management of the disease.

PMID- 9146124
TI  - Summer camps for children and adolescents with kidney disease.
AB  - Summer camps, sports camps, and residential camps are readily available to
      children and adolescents across the country. However, children and adolescents
      with end stage renal disease (ESRD) may not be able to participate in summer camp
      experiences because of specialized medical needs (e.g., dialysis or
      immunosuppressive medications) and concerns about abilities to keep up with camp
      activities. With enhancements in pediatric nephrology care in the past 10 years,
      patients can be expected to attend school full time and participate in peer
      activities. In addition, attendance at summer camps becomes a possibility for
      these children, particularly camps aimed at children with ESRD. Twenty pediatric
      nephrology centers in North America were surveyed about their participation in
      summer camp programs. This article reviews these and attempts to elucidate the
      values of summer camp programs for pediatric ESRD patients.

PMID- 9146125
TI  - Challenges in delivering peritoneal dialysis to a premature infant.
AB  - The proposed outcomes for C.Q. were achieved. Communication between dietician,
      neonatal intensive care and pediatric nursing staff, pediatric nephrology nurses
      and physicians played a critical role in providing optimal care for C.Q. Due to
      her multiple problems, it was imperative that all disciplines collaborate and
      coordinate their care. The meticulous supervision by the staff nurses allowed
      this tiny patient to overcome her multiple problems. Careful follow-up included
      monitoring nutritional markers, laboratory results, and adequacy of dialysis. It
      is also important to note that open communication by the nephrology nurses allows
      small patients like C.Q. to have enhanced quality of life at home with their
      families. C.Q. is now a thriving infant, cared for by her mother at home.

PMID- 9146126
TI  - Use of ascorbic acid to remove chloramine from dialysate water.

PMID- 9146127
TI  - Customer-oriented attitudes and skills for staff members.

PMID- 9146129
TI  - Culture and advance directives.

PMID- 9146128
TI  - Developing a critical pathway for vascular access management. Case study of the
      anemic patient.
AB  - Critical pathways define the essential components of care that must occur within
      a specific time period to achieve a desired outcome. At Vanderbilt University
      Medical Center, a multidisciplinary critical pathway was developed to manage
      vascular access procedures. Before the pathway was instituted, the average cost
      for an inpatient vascular access procedure ranged from $10,000 to $20,000. After
      the pathway had been used for eighteen months, 95% of these procedures were done
      on an outpatient basis, and the average cost had decreased to between $4,000 and
      $5,000. A subjective survey revealed an increase in patient and family
      satisfaction with provided services.

PMID- 9146130
TI  - Management of the surgical patient with asthma.
AB  - "Asthma is a common and chronic inflammatory condition of the airways whose cause
      is not completely understood. As a result of inflammation the airways are
      hyperresponsive and they narrow easily in response to a wide range of stimuli".
      There are almost 3 million asthma sufferers in the UK with up to 5% of adults and
      5-10% of children having asthma. It is not surprising then that a significant
      number of patients who come into hospital for either elective or emergency
      surgery will be asthmatic.

PMID- 9146131
TI  - A diploma in perioperative practice for the millennium?

PMID- 9146132
TI  - The Daisy Ayris Memorial Lecture. The European influence.

PMID- 9146133
TI  - What's your angle?

PMID- 9146134
TI  - Medieval surgery.
AB  - How many readers of this journal have tried to imagine what surgery was like
      before the sophisticated technical developments described in its pages? Not just
      before such important advances as blood transfusion, anaesthesia and asepsis, but
      long before the evolution of teaching hospitals, with their steeply-raked
      operating theatres, crowded with students and other curious onlookers. Today's
      medical experts tend to dismiss early practitioners of surgery as "primitive" and
      "unscientific" because their ideas about human physiology (which appeared
      perfectly rational at the time) now seem tinged with superstition. Surgery in
      medieval England was certainly very different from anything we are likely to
      encounter in the sanitized environment of the modern hospital, yet it was well
      organised, carefully regulated and made great demands upon the skill and
      dedication of the men and women who plied a difficult trade, in which the rewards
      could be considerable but the risks even greater.

PMID- 9146135
TI  - Sudden death and the theatre nurse.
AB  - Sudden death, by definition, is a death that is unexpected and for which the
      people concerned are unprepared. In one sense, all deaths are sudden, after all
      it takes only a few seconds to stop breathing. But many deaths are expected such
      as when a person has been ill for a long time or is very old and infirm, or has a
      known terminal condition. Should a normally healthy person die unexpectedly in
      the operating theatre during routine surgery or as a result of trauma then this
      may be described as 'Sudden Death'.

PMID- 9146136
TI  - The principles of pharmacology (3).
AB  - This is the concluding part of a series of articles which examines the principles
      of pharmacology. This paper reviews the potential variability of an individual's
      response to drugs and the unwanted adverse reactions that may occur. Following
      this theme, the pharmacological considerations of the extremes of age will be
      briefly reviewed and the implications for perioperative practice highlighted. The
      reader is encouraged to use the reference list as indicative reading and complete
      the questions that appear during the text.

PMID- 9146137
TI  - National committees: notes for novices.

PMID- 9146138
TI  - What is a computer?

PMID- 9146139
TI  - Reflection of an experience!
AB  - Reflection has become an everyday word in the nursing press and literature, but
      what does it mean exactly to us as nurse practitioners, and how can we actually
      use it to good effect in our everyday working practice? Much of the literature
      available on reflection is both complex and abstract. The aims of this article
      are to give an insight into the topic through reviewing the literature and then
      presenting a personal example of 'reflection of an experience'.

PMID- 9146140
TI  - Breast cancer audit--the Isle of Wight experience.
AB  - The United Kingdom has the unwelcome distinction of having the highest incidence
      of breast cancer in the world (World Health Organisation Statistics Annual 1985).
      Publication of the Forrest Report in 1986 (Forrest, 1986) stimulated the
      introduction of the Breast Screening Programme in 1988.

PMID- 9146141
TI  - Perioperative post graduate education.
AB  - This article describes post-graduate perioperative education in Australia at the
      Australian Catholic University and St. Vincent's Public Hospital: The Graduate
      Certificate in Perioperative Practice. The Australian Catholic University
      operates from eight campuses along the east coast of Australia. There are
      approximately 9000 students along with 1000 staff. The University consists of
      major faculties that all have clear relevance to the workplace-namely Arts and
      Sciences, Education and Health Sciences. Qualifications are offered at
      Certificate of Doctoral level studies in the areas of business, education,
      ethics, human movement, management, information systems, music, nursing,
      religion, social work and theology.

PMID- 9146143
TI  - PC heaven--Part 2. Buying a computer.

PMID- 9146142
TI  - Homeostasis--the key concept to physiological control.
AB  - Immunity is a response to the invasion of the body by non-self antigens (Figure
      8). Immunity is characterised by being: Xenophobic--it distinguishes self from
      non-self components. Adaptive--it produces a response to an antigenic invasion.
      Highly specific--its response is personal for different antigenic insults.
      Anamnestic--its memory component allows the occurrence of primary and secondary
      responses.

PMID- 9146144
TI  - Breast cancer. Mortality and morbidity.

PMID- 9146145
TI  - Learning to care in theatre.

PMID- 9146146
TI  - The Theatre Liaison Nurse--taking trauma through the crisis.

PMID- 9146147
TI  - Attendance of company representatives in the operating theatre.

PMID- 9146148
TI  - Using pulse oximetry in the home.
AB  - As complex patients require more sophisticated nursing care and equipment to stay
      at home, home care nurses must be able to make detailed, objective assessments.
      Pulse oximetry provides a tool to objectively assess oxygenation in the home.
      This article reviews how pulse oximetry works, how to interpret the results based
      on the patient's blood oxygen-carrying capacity, and technical aspects of using
      pulse oximetry in the home, including sources of inaccuracy in measurements and
      basic troubleshooting. These pulse oximetry principles are applied in the home
      care setting in three case studies.

PMID- 9146149
TI  - 1997 Joint Commission on Health Care Organizations home care standards: what's
      new?
AB  - Even though there are no new home care standards for 1997, there are some changes
      in the standards' interpretations and documentation expectations. Not all of the
      new interpretations are stricter interpretations. In fact, most of the new 1997
      standards interpretations are more flexible. New interpretations for other
      problematic home care standards will be addressed in future columns.

PMID- 9146150
TI  - Using a creative teaching process with adult patients.
AB  - Because the patient or caregiver must manage healthcare needs after the nurse has
      left the home, patient education is an important component to home health nursing
      (Rice, 1996). Fortunately, patient teaching is ideal for home healthcare. To make
      the most of the home learning environment with adult patients, the nurse must
      assess, design, develop, implement, and evaluate an individualized patient
      teaching plan. Throughout the ADDIE process, the nurse manipulates and integrates
      the home environment to maximize the possibility that the patient will accept,
      remember, and apply the information presented. Taking into account how adults
      learn, the nurse provides relevant problems and situations for the patient to
      practice newly acquired knowledge and skills. The instruction presents learners
      with alternatives to their current ways of thinking, behaving, and living
      (Brookfield, 1986). Given the information and the tools needed to regain a sense
      of control and experience life safely, within their abilities of medical illness
      or injury, informed adult patients are likely to experience fewer complications
      and enhanced self-esteem. For pertinent, timely, and personal healthcare
      instruction, there is no place quite like home.

PMID- 9146151
TI  - Home care triage nurse.
AB  - As a TN who began in a position with little insight into the expectations and who
      has been able to develop the system into one that ideally meets the needs of our
      home care institution, I always feel challenged. Initially, my concern was that I
      would lose touch with what was new and would lose my clinical skills. To the
      contrary, I feel that I have honed my skills. By understanding the steps to
      procedures and their rationale, disease processes, symptoms, treatment regimes,
      and through continuing education, I have become confident in teaching patients
      and caregivers over the phone. Although the staff includes those in each of our
      branches, I am able to have contact with them all now more than ever. Because we
      known as home care workers that it is difficult to develop relationships and
      trust among staff members because of the independent nature of home care nursing,
      forging a relationship based on trust between the staff members and the TN is
      crucial for delivering consistent patient care 24 hours a day, 7 days a week. It
      is note-worthy that to develop the TN system effectively, I was granted autonomy
      and lent support by the agency administration and management. This autonomy
      continues to be instrumental for success.

PMID- 9146152
TI  - The Internet--a home care nursing clinical resource: Part I.

PMID- 9146153
TI  - A study of the relationship between home care services and hospital readmission
      of patients with congestive heart failure.
AB  - Patients with congestive heart failure (CHF) constitute a substantial portion of
      the caseloads of home care agencies. Home care is one strategy suggested for
      delaying or preventing hospital readmissions. This study examined the
      relationship between home care nursing services and hospital readmissions after
      1176 discharges of patients with a primary diagnosis of CHF. It also described
      the home nursing care of such patients. Findings indicate that patients receiving
      home care nursing services were readmitted to the hospital significantly less
      often within a period of 90 days after hospital discharge.

PMID- 9146154
TI  - Dealing with aggressive patients and avoiding overinvolvement.

PMID- 9146155
TI  - Bringing managed care home: strategies for success.
AB  - Managed care continues to increase in market share and greatly influence the
      provision of home care services. Written from a home care nurse's experience and
      perspective, this article gives an overview of the current managed-care climate
      and suggests strategies agencies and nurses can use to be successful in working
      with this market.

PMID- 9146156
TI  - Home care nurses--an endangered species?

PMID- 9146157
TI  - Basic musculoskeletal assessment: tips for the home health nurse.
AB  - Home care clients typically present with functional deficits that are frequently
      attributable to musculoskeletal abnormalities. This article teaches the home care
      nurse how to conduct a basic musculoskeletal assessment and how to use the
      findings to develop a thorough plan of care for the home care client.

PMID- 9146158
TI  - Joint Commission on Accreditation of Healthcare Organizations' infection control
      requirements: fact or fiction?

PMID- 9146159
TI  - Scaffolding the coronary arteries: intracoronary stenting.
AB  - Stenting is a new method for treating coronary artery stenosis. This article
      presents an overview of the rationale for the implantation of stents, the various
      types of stents available, and roles the home care nurse assumes in caring for
      these patients.

PMID- 9146160
TI  - The home healthcare nurse and confidentiality and privacy.

PMID- 9146161
TI  - Tips for using OASIS now.
AB  - The outcome and Assessment information Set (OASIS) is an integral aspect of
      outcome-based quality improvement as described in the Spotlight feature in the
      March 1997 issue of Home Healthcare Nurse. This article shares one agency's
      experience in using the data set and provides creative approaches and tips for
      using OASIS immediately.

PMID- 9146162
TI  - How managed care affects day-to-day operations.

PMID- 9146163
TI  - Mental health services in the home: a balance of sophistication and caring.
AB  - Mental health nursing in the home setting has evolved to a level of expertise and
      specialization to meet the unique needs of clients and the demands placed on the
      providers delivering care. The sophisticated use of assessment tools and
      treatment protocols such as clinical pathways has contributed to the traditional
      caring approaches used by the mental health nurse. In collaboration with
      physicians, the autonomous nature of mental health home nursing is on the cutting
      edge of predicting the needs of the mental health client while providing
      outstanding quality care in a professional and cost-effective manner.

PMID- 9146164
TI  - Humor in the home care office.

PMID- 9146165
TI  - A time for self-care: role of the home healthcare nurse.
AB  - The concepts of self-efficacy and self-responsibility in personal health provide
      the framework for developing cost-effective nursing strategies that have positive
      outcomes for the consumer and the provider Promoting self-care requires that
      nurses be knowledgeable about outcome planning, the teaching-learning process,
      and supportive techniques for ongoing care. The concepts outlined in this article
      can be used to provide care for those who require health promotion, health
      maintenance, and illness management.

PMID- 9146166
TI  - The legacy of Parham vs. J. R.

PMID- 9146167
TI  - Staff members' beliefs about seclusion and restraint in child psychiatric
      hospitals.
AB  - BACKGROUND: Staff members beliefs about seclusion and restraint are influential
      in determining how and when these interventions are employed. Yet there are few
      studies of staff beliefs in individual hospitals and no comparative studies
      across hospitals. OBJECTIVE: To measure staff members' beliefs about the
      rationale for and efficacy of the use of seclusion and restraint with children
      and adolescents. METHODS: A survey of staff members (N = 320) from 13 public and
      private child psychiatric hospitals. RESULTS: Results indicate a low to moderate
      level of confidence among all staff groups regarding the efficacy of seclusion
      and restraint. Staff members from private hospitals were significantly more
      positive in their assessment of these interventions than were staff members from
      the public sector. CONCLUSION: We hypothesize that the persistent use of coercive
      interventions in which staff have a low level of confidence reflect both the
      influence of tradition in the management of aggressive behavior and
      unacknowledged avoidant/coercive staff responses to patents labeled as deviant.
      Differences between the public and private sectors and between hospitals within
      each sector imply that the practice of seclusion and restraint may be
      idiosyncratic to each institution, and suggest the need for a generally accepted
      standard for their use.

PMID- 9146169
TI  - Nursing education and clinical practice on child and adolescent psychiatric
      inpatient services: survey results.
AB  - OBJECTIVE: To evaluate the educational preparation of staff nurses working on
      child and adolescent psychiatric inpatient services. METHODS: A 40-item
      questionnaire was sent to 169 staff nurses in nine institutions. One hundred
      seventeen questionnaires (69.2%) were suitable for analyses. RESULTS: Respondents
      ranged in age from 22 to 52 years (mean = 34.7, +/- 7.43 years) and 87.2% (n =
      102) were women. Seventy-one percent (n = 83) of the respondents agreed that
      basic nursing education inadequately prepared them for work on child and
      adolescent psychiatric inpatient services. Deficiencies were cited in
      psychopharmacology, child psychiatric diagnosis, child psychopathology, and
      milieu treatment. There were few differences across educational type. CONCLUSION:
      Recent advances in psychiatric epidemiology, psychopharmacology, and neuroscience
      merit greater attention in undergraduate nursing education. Child psychiatric
      institutions and professional nursing organizations have a role to play in
      continuing education.

PMID- 9146168
TI  - Parents' perceptions of their child's emotional illness and psychiatric treatment
      needs.
AB  - PROBLEM: The purpose of this study was to describe how parents define their
      child's emotional illness and psychiatric treatment needs. SUBJECTS: The sample
      consisted of 19 parents and one grandparent (N = 20) who had recently admitted
      their child to a short-term psychiatric unit. METHODS: Qualitative methods,
      utilizing a semistructured interview. Data were analyzed using the constant
      comparative method. Substantive codes were combined to derive the key concepts
      and themes in the interviews. FINDINGS: The findings of this study center on
      themes related to parents' efforts to control the current behavioral crisis,
      treatment acceptability, family needs, explanatory formulations, and securing the
      child's future. CONCLUSIONS: Implications for treatment include how nurses might
      tap into parents' perceptions to facilitate parent' professional communication.

PMID- 9146170
TI  - The growth and development of a graduate nursing student--or when you're up to
      your knees in alligators, you forget why you went into the swamp in the first
      place.

PMID- 9146171
TI  - Teaching cultural diversity in a virtual classroom.

PMID- 9146172
TI  - Reaching out to partners.

PMID- 9146173
TI  - Psychological evaluations, referrals, and follow-up of adolescents after their
      exposure to Hurricane Hugo.
AB  - PROBLEM: There is little understanding of adolescent appraisal of stress and
      crisis intervention for adolescents who are exposed to major stress such as that
      of a natural disaster. METHODS: A description of the psychological evaluations,
      referrals, and follow-up assessments made by nurse practitioners (NPs) and a
      nurse psychotherapist (NPT) of adolescents (N = 507) in two South Carolina high
      schools who experienced Hurricane Hugo. FINDINGS: The NPs' evaluations concluded
      that 63 adolescents (12%) exhibited symptoms of psychological distress. The NPs
      referred 36 of these adolescents to high school counselors for minor distress or
      school-related problems and 27 for more intensive clinical evaluation by an NPT.
      Of the 27 adolescents who were referred to the NPT, 10 had symptoms associated
      with adolescent adjustment reaction, 8 showed symptoms of depression, 5 revealed
      symptoms of posttraumatic stress disorder, and 4 complained of serious family
      problems. CONCLUSIONS: Based on these data and the mental processes described by
      these adolescents, the authors propose a model and suggest adolescent appraisal
      of stress and crisis is a critical issue to consider when intervening with
      adolescents who are exposed to major stressors, including those associated with a
      disaster.

PMID- 9146174
TI  - Animal-assisted therapy with hospitalized adolescents.
AB  - PROBLEM: To ascertain the effects of animal-assisted therapy on hospitalized
      adolescents. METHODS: Thirty adolescents hospitalized in a 16-bed psychiatric
      unit. Data collection included patient journals, interviews with 15 patients, and
      anecdotal notes from observations and staff reports. The ethnographic method was
      used for data analysis. FINDINGS: Categories identified from the data include the
      dog as a component of the milieu, as friend, and as therapist. The dog served as
      a catalyst for interactions, and often had human qualities ascribed to him by the
      adolescents. CONCLUSION: This study provides new information that can enhance
      patient care.

PMID- 9146175
TI  - Themes in the bereavement experience of inner city adolescents.
AB  - PROBLEM: There is a lack of information about the bereavement experiences of
      adolescents living in poverty in the inner city. SUBJECTS: Eight bereaved
      adolescents (mean age = 13.5 girls, 3 boys), from poverty-level families,
      attending an inner city junior high school. METHODS: A descriptive design, using
      participant-observation in a semi-structured group setting, data were gathered
      using audiotape recordings of the eight group discussions. FINDINGS: Chaos and
      stress were major themes pervading each discussion session. Lack of family and
      social support, fear for their future, and avoidance as the major coping strategy
      were also themes of the study. CONCLUSIONS: Inner city adolescents need to be
      assessed for loss of significant others. Provision of mental health services in
      schools could provide intervention services to current and future problems.

PMID- 9146176
TI  - Behavioral intervention for children with autism.
AB  - TOPIC: Autistic disorder is a pervasive developmental disorder characterized by
      deviant social interaction, communication, and behavior. It is a lifelong
      disability that affects 2-5/10,000 individuals. Children with autistic disorder
      are increasingly present in all patient care settings. Their behavior is often
      mystifying and overwhelming to professionals. PURPOSE: To offer specific
      information about appropriate intervention strategies that can be applied to
      impatient units, schools, community residences, and homes. SOURCES: Published
      information and clinical experience. CONCLUSIONS: Behavioral treatment methods
      provide guidance for the treatment of children with autism. However, they must be
      adapted to each child's specific circumstances. Additional research is needed to
      refine current behavioral treatment approaches.

PMID- 9146177
TI  - The 104th U.S. Congress: outcomes and alarms.

PMID- 9146178
TI  - Creating an elder sensitive acute care climate: a health care imperative.

PMID- 9146179
TI  - Sharing stories. Group therapy with elderly depressed women.
AB  - As the population ages, nurses are challenged to seek and use relevant and
      effective nursing strategies to assist clients to cope with major life events and
      chronic conditions. Depression in the elderly, particularly among elderly women,
      is increasing. This is a serious problem which pervades community, acute and
      chronic care settings. In order to provide proactive care in the treatment of
      depression, two nurses in a psychogeriatric clinic developed a unique program,
      consisting of 10 weekly group sessions for elderly women with a diagnosis of
      depression. This article describes the formal, content of group sessions and
      outcomes. Key themes that emerged are illustrated by the stories shared by the
      women. These stories were central to shaping the group experience and enhanced
      the learning of group members and facilitators as well. The method of group
      process and insight into dynamic strategies for teaching/learning in the elderly
      are discussed. In conclusion, recommendations for future programs have been
      identified.

PMID- 9146180
TI  - Social interaction among people with dementia.

PMID- 9146181
TI  - Differentiating aggressive and resistive behaviors in long-term care.

PMID- 9146182
TI  - Validation therapy. A review of the literature.

PMID- 9146183
TI  - Intrainstitutional relocation. Effects on residents' behavior and psychosocial
      functioning.
AB  - INTRODUCTION: Relocation effects in the elderly have been a topic of gerontologic
      research for many years. Prior research, however, has focused on individuals who
      could make a cognitive appraisal of the relocation process. With a greater
      prevalence of cognitive impairments and/or psychiatric illnesses in long-term
      care residents, research is needed to clarify the impact of relocation on these
      individuals. OBJECTIVE: The purpose of this study was to determine how
      intrainstitutional relocation affects behavior and psychosocial functioning in
      residents with and without cognitive, mood, and/or psychotic disorders. METHOD:
      This prospective study followed 78 residents being relocated intrainstitutionally
      in a health-related facility that was undergoing major renovations. Medical and
      nursing information was collected at 1 month pre-move and at 1 and 3 months post
      move. Five areas of behavioral and psychosocial functioning (self-care,
      disoriented behavior, depressed/anxious mood, irritable behavior, and withdrawn
      behavior) were assessed using the Multidimensional Observation Scale for Elderly
      Subjects (MOSES). RESULTS: A significant increase was seen in the number of
      medical visits (p = .04) from time of relocation to 1 month post-move. The groups
      diagnosed with mood disorder and psychotic disorder had a statistically
      significant weight loss (p = .04) between 1 month pre-move and 1 month post-move.
      The study revealed an increase in the number of residents who fell immediately
      after relocation, but the increase did not reach statistical significance (p =
      12). Residents who fell after relocation had resided at the facility for a longer
      time than the remainder of the sample (p = .08). Residents with a diagnosis of
      cognitive impairment showed a statistically significant difference in self-care
      (p = 0.01) and withdrawn behavior (p = 0.01) at 3 months post-move. Extensive
      relocation preparation and support may have been the main contribution to
      diminishing the stress of relocation over time and across diagnostic categories.

PMID- 9146184
TI  - A collaborative effort between hospital and long-term care staff for helping
      chronically mentally ill clients.

PMID- 9146185
TI  - How do you deal with an RN family member who attempts to manage the care of his
      or her relative?

PMID- 9146186
TI  - Use of alternative therapies among Mexican Americans in the Texas Rio Grande
      Valley.
AB  - Alternative therapies have gained increasing recognition and usage in North
      America during the past decade. In a descriptive study with a convenience sample
      of 213 Mexican Americans, three research questions were asked: (1) What specific
      kinds of alternative therapies do Mexicans in the Rio Grande Valley use? (2) What
      percentage of the sample group uses alternative therapies? and (3) Do the users
      of alternative therapies self-report these visits to their established,
      conventional, primary health care provider? Findings showed that 44% of
      respondents had used an alternative practitioner one or more times during the
      previous year. The most commonly sought therapies were herbal medicine, spiritual
      healing and prayer, massage, relaxation techniques, chiropractic, and visits to a
      curandero (Mexican folk healer). The majority (66%) never report visits to
      alternative practitioners to their established primary health provider.

PMID- 9146187
TI  - The delivery of culturally sensitive health care to Native Americans.
AB  - Cultural factors significantly influence the Native American's perspectives of
      traditional professional health care practices. To most effectively deal with
      Native American clients, health care providers must understand, respect, and
      demonstrate sensitivity to the values and implications of the Native American
      culture. A basic understanding of a group's cultural beliefs, values, and
      practices will enable the holistic nurse to appreciate the importance of
      appropriate interactions and techniques and, therefore, make health care more
      readily accepted. This article reviews the health and illness beliefs, the
      traditional remedies, the critical need for holistic health care, and the Five
      Great Values that guide Native American behavior. Familiarization with these
      cultural components will facilitate the provision of quality, holistic health
      care through improved interactions with Native American clients.

PMID- 9146188
TI  - A review of prayer within the role of the holistic nurse.
AB  - Prayer is an integral component of the spiritual life of mankind. It is a two-way
      dialogue with God. Clients in crisis may need prayer for encouragement, comfort,
      and support. Holistic nurses may use prayer with clients to positively influence
      how they cope with anxiety relative to illness. Addressing the spiritual needs of
      clients is an important element of care and the use of prayer is supported by
      both informal client responses and scientific research. Additionally, the active
      use of prayer may provide added value and enrichment to the holistic nurse-client
      interaction.

PMID- 9146189
TI  - The experience of self for women who are mothers. Implications for the unfolding
      of health.
AB  - Although the expression and transformation of self is integral to people's health
      and healing experiences, nurses currently lack an in-depth understanding of how
      women who are mothers experience and express themselves. This article presents
      the results of a recent study that examined the lived experience of self for
      mothers. Principles of interpretive phenomenology and feminist inquiry guided the
      investigation. The results of the study describe the nature and experience of
      self for the 7 women/mother participants and highlight the complementary
      relationship between the experience of oneself and the unfolding of health. Three
      essential themes emerged to describe the experience of self, including (a) self
      as a multiplicity of parts, (b) self as a relational process, and (c) self as a
      synthesis. The results illustrate the complementary relationship between health
      and self experience and highlight the nursing imperative of supporting
      women/mothers in their unfolding of self.

PMID- 9146190
TI  - Toward a framework for patient education. An analysis of enablement.
AB  - Patient education is an activity that nurses engage in on a regular basis, yet in
      the literature it is seldom examined as a patient-centered process. The desire to
      describe the process of patient education in terms that were not content-driven
      was the guiding force for an examination of the concept of enablement. The
      purpose of this article is to describe an analysis that resulted in a definition
      of enablement and the identification of three components: means, abilities, and
      opportunities. Model, related, and contrary cases are provided. The findings of
      this examination are used to propose a potential framework for designing,
      implementing, and evaluating patient education across content areas.

PMID- 9146191
TI  - Health risks of homeless adolescents. Implications for holistic nursing.
AB  - Although the exact number of homeless adolescents is unknown, it is estimated
      that this population may exceed 2 million. Literally living on the streets,
      homeless youth are at risk for a variety of physical, psychosocial, and spiritual
      health problems. Many engage in "survival sex," exchanging sexual favors for
      necessities of food, clothing, and shelter. Such risky sexual behaviors make them
      vulnerable to sexually transmitted diseases, including human immunodeficiency
      virus (HIV) and acquired immunodeficiency syndrome (AIDS), and unintended
      pregnancies. Many have serious, diagnosable mental health problems, whereas
      others suffer various consequences of substance abuse. There is a need for
      comprehensive and holistic health care services, for which the majority of
      homeless youth have very limited access. Holistic nursing can provide creative
      interventions for thus vulnerable population.

PMID- 9146192
TI  - The goddess and healing. Nursing's heritage from antiquity.
AB  - In prehistoric and ancient historical times, it was the Goddess who oversaw the
      health and well-being of human beings and women who controlled many healing
      processes, rituals, and practices. The professions of nursing and other health
      care fields owe much to this history yet have moved away from it in significant
      ways. Drawing on literary and archaeological sources, this study traces the
      history of healing in Graeco-Roman antiquity, describes the role of the Goddess
      and women in the healing function, discusses the communal aspects of healing both
      in the ancient world and in the modern West, and provides connections between the
      past and present that may empower today's nursing professionals.

PMID- 9146193
TI  - Florence Nightingale and holistic philosophy.
AB  - Florence Nightingale lived at a time when allopathy and homeopathy were competing
      for dominance in medical care. Nightingale's philosophy of health and healing was
      more similar to the holistic philosophy of homeopathy than to the mechanistic
      philosophy of allopathy. Why, then, did Nightingale align organized nursing with
      allopathic medicine? Perhaps Nightingale, always the pragmatist, understood that
      allopathy would gain the dominant position in medicine. Perhaps aligning nursing
      with allopathy was a way to ensure the survival and legitimacy of nursing as a
      profession. Modern nursing can reconnect with Nightingale's holistic philosophy
      by preparing graduates conversant with holistic philosophy and by encouraging
      research that focuses on how the natural healing process is facilitated.

PMID- 9146194
TI  - Embodied soul. The focus for nursing praxis.
AB  - This article explores the nature of embodied soul as a phenomenon of concern to
      nursing. Examples of the body/soul debate from early Greek philosophers to the
      present day are examined. Early writings on the subject echo in medieval writings
      and in present-day knowledge of neuroscience and physics, as well as in the
      writings of Merleau-Ponty. The author proposes that nursing embrace the concept
      as it relates to Berry's patterns of differentiation, subjectivity, and communion
      in the universe. These patterns exist from the cellular to the cosmic level. It
      is through the embodied soul that one engages in this process. The works of
      selected nurse theorists are examined as they relate to the topic. Both the
      subject of the client and of the nurse as embodied souls are addressed.

PMID- 9146195
TI  - Use of neonatal boundaries to improve outcomes.
AB  - Technological advances have dramatically improved survival rates for the high
      risk infant, yet developmental delays are common due to complications resulting
      from immature organ systems. The neonatal intensive care unit environment itself
      may pose barriers to optimal development of these infants. The purpose of this
      study was to investigate the effects of an oval-shaped cloth nest to make the
      environment less stressful and enhance neonatal development. Specifically, the
      study hypothesized that infants who were placed in the cloth nest would gain more
      weight and would have shorter lengths of hospital stay than would infants
      receiving routine care. A total of 102 healthy infants ranging from 26 to 31
      weeks of gestation were recruited into the study. No significant differences were
      found in the groups on amount of weight gained. Infants who were placed in the
      cloth nest actually had longer hospital stays than did infants receiving routine
      care. Perhaps infants who received routine care received more touch than did
      nested infants, and the touch may have facilitated development as measured by
      length of stay.

PMID- 9146196
TI  - A narrative approach to quality care in long-term care facilities.
AB  - The negative effects of institutionalization caused partially by homogeneity and
      uniformity of care prompts the exploration of personal and common meanings of
      nursing home residents. This study is viewed as an initial step in providing
      quality care as defined by the resident. Personal and common meanings embedded in
      the lived lives of five older women residing in a long-term care facility are
      interpreted using a seven-stage Heideggerian hermeneutical phenomenological
      approach. An unstructured modified life review format is used to interview each
      participant on three separate occasions. Three constitutive patterns emerge:
      dwelling in remembering, living relatedly, and being after loss. These patterns
      endure across the life span of each woman and continue to endure after admission
      to the facility. The revelation of common and personal meanings provide new
      possibilities for the transformation of nursing practice to ensure quality care
      from the perspective of what is considered meaningful to each resident.

PMID- 9146197
TI  - Spirituality in terminal illness. An alternative view of theory.
AB  - I use data and insights gained from 10 years of research and practice on
      psychosocial and spiritual aspects of living with HIV to outline a critique of
      extant knowledge on spirituality and to propose an alternative. Nurses are in an
      excellent position to experience the human spirit. We can use the resultant
      understandings to be present with others and to become more self-aware and self
      loving. I present here my philosophy and personal rules for understanding the
      spirit that were taught to me by patients and knowledgeable research participants
      as they helped me to see how my professional objectivity and application of
      professional knowledge were anathema to their self-discovery. I present a
      critique of some of the confining aspects of nursing theory, particularly that
      which is built on developmental frameworks to show how our vision is skewed
      negatively by these frameworks, and how it may cause us to look down at patients
      rather than at them as equals.

PMID- 9146198
TI  - Evaluating the benefits realized from a nurse management information system.
AB  - The information requirements of nurse managers have been uncreasing rapidly in
      recent years. The demand for access to relevant and accurate information has led
      to the development of computerized information systems for use a ward level.
      However, once implemented, few information systems have been evaluated to
      identify the benefits that will be realized. This paper presents the results of a
      study carried our in Oxford to evaluate one nurse management information system
      using a multi-method approach to identify ways in which returns may be
      manifested. It suggests that evaluation should be an active process planned at
      the same time is defining information requirements.

PMID- 9146199
TI  - The role and resources required for the introduction of generic ward assistants
      using GRASP systems workload methodology: a quantitative study.
AB  - Non-nursing workers have been advocated as a means of ameliorating high nursing
      utilizations, whether the cause be budgetary or the inability to recruit trained
      staff. The creation of a generic worker who would undertake domestic, catering
      and non-nursing activities has been seen as a way of improving the ward
      environment and releasing trained staff and health care assistants from non
      nursing activities, GRASP systems workload methodology was used to develop a job
      description and a tool to quantify the resources needed to introduce such
      workers. A quantitative research study and activity analysis was carried out on
      two sample wards to validate the tool. The results were validated by a 'within
      study' audit process comparative analysis and an activity qualitative analysis
      using a Likert attitudinal scale. Empirical analysis of the study's findings and
      the financial consequences were predicted across the Trust.

PMID- 9146200
TI  - Vulnerable families: a study of health visitors' prioritization of their work.
AB  - Changes in the NHS have supported the idea of targeting health services to those
      in greatest need. This has meant that health visitors are increasingly having to
      identify 'vulnerable' families in need of increased health visiting intervention.
      This paper reports on a qualitative study undertaken in order to explore the ways
      in which health visitors plan and organize their work in relation to the concept
      of vulnerability. Focus groups and semi-structured interviews were carried out
      with health visitors from two separate geographical areas, one an inner city area
      and the other suburban, in order to explore the criteria by which health visitors
      define vulnerability and decide to increase their levels of intervention to
      particular families. It was found that vulnerability was extremely difficult to
      define but that the health visitors used criteria which were appropriate to the
      particular localities in which they worked to identify vulnerable families and to
      increase their levels of intervention to those families. Health visitors were
      targeting their services within a framework of a basic minimum service to all and
      were assessing the health needs of individuals or families rather than planning
      their work on the basis of community or practice profiles.

PMID- 9146201
TI  - Communication between nurses and nurse managers: a case study from an NHS Trust.
AB  - The role of effective communication in promoting organizational efficiency and
      effectiveness is being increasingly recognized. This paper proposes a
      communication audit methodology as a useful means of examining the quality of
      communication between nurses and their managers. Utilizing a case study
      methodology, results from an exploratory study are presented and discussed. These
      data suggest that significant problems in this field currently exist. The general
      applicability of the findings throughout the NHS are considered, and proposals on
      how relationships and communication could be improved are examined.

PMID- 9146202
TI  - Changing nursing practice through continuing education: a tool for evaluation.
AB  - In light of the current cost-orientated, rapidly changing health service,
      continuing education providers are challenged to achieve the greatest benefits
      for the service. Given this culture it is argued that it is essential for nurses
      to acquire the skills to continually learn, and that for managers there is seen
      to be a measurable change in a recommended practice or behaviour. To meet these
      challenges it is essential that continuing educators plan, implement and evaluate
      programmes in partnership with clinicians and managers. A literature review
      revealed that most evaluations did not address whether continuing education has
      resulted in a change in practice. This paper describes a study on the use of goal
      attainment scaling as an evaluation tool to measure changes in learner behaviour
      and as a means of promoting self-determination among the participants. It is
      proposed that goal attainment scaling can be used to measure changes in
      participant behaviour following an educational programme. In addition, this
      analysis of participant interviews indicates the tool's usefulness as a self
      reporting instrument and this appears to foster the skills of self-assessment and
      appraisal of performance.

PMID- 9146203
TI  - Do nurses really care? Some unwelcome findings from recent research and inquiry.
AB  - This paper examines the position of nursing as a caring profession, in terms of
      an ethical code that stresses collegial relationships, a sense of obligation to a
      clientele that is realized in terms of expert service, and a clearly defined body
      of research-derived knowledge as the basis for practice. It also investigates the
      substance of the claim that nursing has tended to arrogate to itself another
      operational distinction-its exclusive capacity to blend physical and emotional
      support into care. A review of recent research and investigation, undertaken in a
      number of countries, suggests that nursing as practiced, rather than as
      theorized, fails to fulfil its wider professional aspirations, and to fulfil its
      caring rhetoric. A related paper will consider how the absorption of nursing into
      higher education might begin to play a part in developing and consolidating the
      professionalization of nursing.

PMID- 9146204
TI  - Beyond hierarchy: working on the edge of chaos.

PMID- 9146205
TI  - The introduction of generic workers into the ward team: an exploratory study.
AB  - This study arose from a quantitative study that defined the role and resources
      required for the introduction of generic workers into the ward team. A month's
      trial was conducted to explore the staff attitudes and perceptions associated
      with such an introduction, thereby identifying potential problems and benefits
      that may influence successful introduction into the ward team. A small convenient
      sample that included trained, untrained and domestic staff was used. The
      methodological strategies in the study were semi-structured interviews, pre- and
      post-trial, and non-participant observations during the trial. The data obtained
      were transcribed and analysed using 'thematic content analysis' and 'within
      method triangulation'. The findings indicated positive support for the
      introduction of such workers and the transfer of responsibility from a central
      domestic team to the ward manager. The ward environment improved and nursing
      staff were freed from non-nursing activity, leaving more time for patient care.
      Recommendations to facilitate the smooth introduction of these workers are stated
      within the study and are now in place within the Trust. The introduction of these
      workers has been agreed and a staggered roll out of the project is underway in
      all wards across the Trust.

PMID- 9146206
TI  - Promoting reflective practice through structured clinical supervision.
AB  - This paper outlines some early issues from a research project that is part of a
      North West Regional Health Authority pilot study on clinical supervision. The
      aims of the study and the research methodology utilized are discussed. The
      experiences of both a sister from a busy accident and emergency department and a
      practice nurse in the community are examined consecutively as supervisor and
      supervisee.

PMID- 9146207
TI  - Accuracy in workload measurement: a fact or fallacy?
AB  - As the drive within a market-led National Health Service is towards cost
      efficiency and through-put, nurses are now more than ever having to 'prove their
      worth'. This has led to various workload measurement systems being used
      throughout nursing. Before examining the accuracy of these measurement tools this
      paper attempts to define workload and investigates how measurement is limited by
      an unclear definition of what 'nursing' actually is. There is little argument as
      to some of the beneficial effects of monitoring workload where changes in
      practice, rostering, skill mix and establishments have occurred. It is, however,
      necessary to examine the accuracy of workload measurement within the current
      framework of nursing to see if it is the promised panacea. The issues surrounding
      patient dependency and professional judgement are discussed and the seeming
      unacceptability of such 'soft data' to non-nursing personnel. Both the 'bottom
      up' and 'top-down' approaches of workload measurement are explored within the
      context of equity, neutrality and bias. The conclusion is drawn that accuracy in
      nursing workload measurement is not possible in the current economic climate and
      that a compromise solution that uses patient dependency as an assessment tool is
      the best that can be hoped for without limiting nursing to inflexible and
      restrictive practices.

PMID- 9146208
TI  - Targeted goal setting: helping nurses manage a turbulent work environment.
AB  - Nurses in a mid-sized Midwestern US hospital were surveyed to investigate the
      interrelationships among workplace locus of control [WLOC], preference for
      proximal and distal goals, and goal setting behaviour. Correlational results
      found preliminary support for the idea that knowledge regarding an individual's
      WLOC orientation may help supervisors optimize goal setting with their nursing
      staff. Nurses with an internal WLOC engaged in more long-term, short-term, and
      overall goal setting behaviour compared to their external WLOC counterparts.
      Nurses with an internal WLOC also reported a greater preference for working with
      distal goals and perceived greater control over setting their goals compared to
      nurses with an external WLOC orientation. Contrary to expectations, supervisors
      were not more likely to possess an internal WLOC orientation or set more goals
      compared to non-supervisory personnel. Nursing supervisors did, however, perceive
      themselves as having significantly greater control over goal setting than non
      supervisors. Based upon these findings, recommendations are proposed to help
      nursing supervisors work with their staff to optimize performance.

PMID- 9146209
TI  - Do nurses really care? An agenda for higher education following recent mergers.
AB  - This paper considers how the mergers of colleges of nursing into higher education
      may offer an opportunity to address the situation revealed in a previous paper,
      which suggested that nursing as practised, rather than as theorized, fails to
      live up to its claim to be regarded consistently as a caring profession. The
      economic position in which higher education currently finds itself, and which
      impacts on mergers, is summarized before reforms to nurse education are
      considered, in terms of their implications for students, staff, research, and the
      courses themselves. The agenda for change is substantial and urgent. The paper
      concludes by maintaining that the absorption of colleges of nursing into higher
      education is to be seen, not as a threat, but as an unprecedented opportunity for
      nursing to begin to realize fully its professional aspirations.

PMID- 9146210
TI  - How to translate nursing care into costs and staffing requirements: part two in
      the Zebra system.
AB  - The purpose of this paper is to describe part two of the Zebra system-the
      activity study: how such a study can be conducted, which requirements must be met
      and how the data are processed and can be used. The activity studies described
      were conducted in two of the wards of the oncology department in the University
      Hospital of Lund, Sweden. The results of the studies make it possible to
      calculate the distribution of different activities for nurses and practical
      nurses during 24 hours and the total nursing care minutes per patient and
      category of care. Together with the patient classification, part one in the Zebra
      system, it is possible to calculate nursing costs per patient stay and the
      patients'staffing requirements. It will be possible to relate nursing costs and
      staffing requirements to actual nursing care given instead of fixed standard
      costs and staffing figures.

PMID- 9146211
TI  - Hepatitis B vaccine for school staff at risk.
AB  - Even though the course of hepatitis B infection at all ages of the individual is
      well known, the mode of transmission-except during infancy-is quite unclear in
      many cases. In this article, the transmission of the virus from student to staff
      members is discussed, particularly in relation to mainstreamed students, as well
      as other populations of children among whom the prevalence of HBV is high. These
      factors are considered in deciding when to use the vaccine, which is known to be
      very effective.

PMID- 9146212
TI  - Problems encountered by parents and guardians of elementary school-age children
      in obtaining immunizations.
AB  - This study surveyed 265 parents of children in kindergarten through third grade
      in an urban New Jersey public school to determine problems encountered in
      obtaining regular immunizations. The most frequent reasons parents failed to
      obtain immunizations were cost, lesser use of WIC and AFDC, and lower perceived
      susceptibility of child to consequences of disease.

PMID- 9146213
TI  - Development of a school nurse education model.
AB  - One reason that school nursing education programs vary from one geographic region
      to another is the difference in requirements for nurse certification by the
      different state boards of education. This has led to fragmentation and
      conflicting beliefs between the education and nursing communities about what
      should be included in a core curriculum. Changing family structure and health
      care needs of children today demand a more specific health focus in the education
      of school nurses. A recently-developed curriculum used the basic nursing core of
      a baccalaureate nursing program to identify the outcomes of school nurse
      education as specified by the professional bodies of the ANA and the NASN. The
      model incorporates only education course work that does not duplicate that in the
      BSN program.

PMID- 9146214
TI  - Anticonvulsant medications: new drug update.

PMID- 9146215
TI  - A comparative analysis of PC-based school health software.

PMID- 9146216
TI  - Gang membership and student behavior: nursing's involvement with prevention,
      intervention, and suppression.
AB  - Gangs are alive, and growing stronger each day, as they infiltrate all
      socioeconomic levels of most towns, cities, and metropolitan areas. This is the
      first of two articles in this issue discussing students and gang membership and a
      school nurse's involvement with gang prevention, intervention, and suppression.
      It is also about a large metropolitan school district's proactive approach to
      gang prevention, which includes a meaningful partnership involving the family,
      community, and school. The program is a comprehensive developmental guidance
      program to promote pro-social behaviors, equip students with refusal skills, and
      encourage problem-solving strategies that enable students to avoid engaging in
      high-risk activities.

PMID- 9146217
TI  - D-TAG: erasing the tag of gang membership.
AB  - Gangs are noted for establishing their territory, flaunting gang affiliation,
      intimidating nonmembers, and documenting their "services performed." These
      examples are a few reasons for the practice of "tagging," the labeling of an
      area, person, or object with gang-related graffiti or markings, such as tattoos.
      This article describes a school nurse's response to gang "tagging" and her
      efforts to assist former gang members who request removal of their tattoos, to
      get them removed-in essence to D-TAG themselves from their gang affiliation. D
      TAG is a volunteer rehabilitation program utilizing family and community
      interaction to support gang tattoo removal and direct activities away from gang
      affiliations toward alternative educational programs and life styles.

PMID- 9146218
TI  - Considering school health program screening services as a cost offset: a
      comparison of existing reimbursements in one state.
AB  - This paper reports results of an analysis of the approximate costs of Colorado
      school health program screening activities during the 1993/94 school year had
      they been conducted elsewhere in the public or private sectors. School nurses and
      health aides performed 1,161,779 screening procedures during the year, an average
      of 1.93 per child enrolled in school districts throughout the state. Charges for
      Current Procedures Terminology (CPT) codes, which correspond to school health
      program screening activities, were used to approximate market value. Conservative
      assumptions were made regarding provider skill and time requirements as well as
      student service utilization profiles. The general dimension of the contribution
      of school health screening activities was found to be impressive.

PMID- 9146219
TI  - Promoting the construction of an optimal nurse's office facility: one school
      district's experience.
AB  - This paper details recommendations for updating or constructing nurses' offices
      based upon a descriptive study done in one midwestern school district. It
      contains suggestions regarding size, location, and equipment needed. It also
      addresses the communication process needed to persuade a board of education and
      school administration that nursing facilities must be a priority in order to meet
      the health needs of students.

PMID- 9146221
TI  - Preparing for the next millennium--a practice issue.

PMID- 9146220
TI  - A health care plan for the student with diabetes.
AB  - This article presents a generic healthcare plan for the student with diabetes.
      This plan provides the basis for comprehensive assessment and subsequent
      interventions and evaluation for the student with diabetes in the care of the
      school nurse. For this plan to be useful, it must be tailored to the student's
      individual needs. Individual problems must be identified and addressed, resulting
      in an Individual Healthcare Plan (IHP). The IHP presented includes an emergency
      health plan for treatment of hypoglycemia; management of diabetes in schools,
      including glucose monitoring and insulin administration; education regarding
      diabetes; and psychosocial assessment of students with diabetes.

PMID- 9146222
TI  - Administrative student information management software (AS/IMS) for school nurse
      record keeping and reporting.

PMID- 9146223
TI  - The babymilk question.

PMID- 9146224
TI  - How mothers choose babymilk brands.
AB  - Babymilks which had been on the market for many years were the most highly
      regarded by the women. Midwives had a greater influence in brand choice than
      health visitors, although overall the women's sisters appeared to be the most
      influential. Women expressed a need for more information regarding the
      nutritional content and differences between various babymilks, but from an
      unbiased source. The effect of subliminal advertising on the postnatal wards
      (i.e. by using ready-to-feed bottles of babymilk) was highly significant. There
      is no doubt that there is deliberate confusion of brand name advertising with
      impartial information.

PMID- 9146225
TI  - Client-held notes: talisman or a truly shared resource?

PMID- 9146226
TI  - Sounding off.

PMID- 9146227
TI  - Access to justice.

PMID- 9146228
TI  - Disabled women and maternity services.

PMID- 9146229
TI  - Nuchal screening, just what some women need?
AB  - Nuchal screening has the following advantages: Non invasive. First trimester
      procedure. Results are obtained quickly. 80-90% detection rate for Down's
      Syndrome.

PMID- 9146230
TI  - RCN nurse ROM.

PMID- 9146231
TI  - RCN Midwifery Society.

PMID- 9146232
TI  - HIV and women using empowerment as a prevention tool.

PMID- 9146233
TI  - American nurses for American men. A World War I diary.

PMID- 9146234
TI  - Are ADNs prepared to be home health nurses?

PMID- 9146235
TI  - The future of associate degree nursing.

PMID- 9146236
TI  - Georgia's RN-BSN articulation model.

PMID- 9146237
TI  - Nursing partnerships: education and practice.

PMID- 9146238
TI  - Mystery of the week: a teaching tool for occupational/environmental health.

PMID- 9146239
TI  - Proactive wound care conference: a teaching strategy.

PMID- 9146241
TI  - Accessing nursing literature: a software review.

PMID- 9146240
TI  - An organizational grid for clinical experiences.

PMID- 9146242
TI  - Perspective transformation: challenging the resocialization concept of degree
      seeking registered nurses.
AB  - Registered nurses, who are already socialized into the profession, do not
      necessarily become 'resocialized' when they return for further education. They
      may, however, change or transform their perspective of nursing, nursing roles,
      and themselves. The authors argue that transformation of perspectives, rather
      than socialization, is a more appropriate framework for future research with this
      population of learners.

PMID- 9146243
TI  - From surgery to the home.

PMID- 9146244
TI  - Quantifying class participation.
AB  - Student participation in classroom activities is frequently considered part of
      the evaluation of a student's performance. However, the quality of a student's
      contribution can be difficult to assess. The Evaluation of Class Participation
      tool was developed to quantify expectations of student preparation and
      participation.

PMID- 9146245
TI  - Work sheets that assist the student in lecture, review, and testing.

PMID- 9146246
TI  - Service-learning within the nursing curriculum.
AB  - Students at all levels are being encouraged to offer public service in their
      communities. Yet, including service-learning courses in a nursing education
      program is rare. The author outlines why and how one department of nursing
      successfully incorporated a service-learning course into their curriculum.

PMID- 9146247
TI  - The Iowa Articulation Story. Collaboration works.
AB  - Historically, Iowa has had a majority of diploma and associate degree nursing
      graduates. Although educational mobility for registered nurses to obtain
      baccalaureate nursing degrees was available in Iowa before 1991, direct nursing
      education articulation did not exist. The impetus for developing a statewide
      nursing articulation plan to facilitate the entry of registered nurses to
      baccalaureate nursing programs was the result of a recommendation from the Iowa
      Board of Nursing's 1988 Statewide Plan for Nursing. The Iowa Articulation Plan
      for Nursing Education: RN to Baccalaureate, implemented in 1991, resulted from
      collaboration among nurse educators from all levels of nursing and nursing
      service representatives. The plan consists of four separate options and can be
      adapted for use in other parts of the country. The Iowa articulation story
      describes the process used and outcomes achieved when nurses collaborate to
      advance nursing education.

PMID- 9146248
TI  - Unleashing the power of memory. The mighty mnemonic.
AB  - The pace and intensity of contemporary nursing education may contribute to
      student difficulties with efficient learning and memory processing. Chronic
      learning problems can cause students to develop feelings of burnout and decreased
      motivation. The author describes how a novel learning strategy, the mnemonic, can
      help students learn more effectively and process information in a enjoyable,
      memorable way.

PMID- 9146250
TI  - A meaningful clinical experience in home healthcare for associate degree graduate
      nurses.
AB  - Associate degree nursing (ADN) students need exposure to community-based clinical
      settings to prepare them for changing practice environments. In response to that
      need, a discrete, clinically-focused, home healthcare course was developed and
      offered to recent ADN graduate nurses. Emphasis was placed on active
      participation of the client and family in care giving activities. Students were
      involved in teaching and demonstration, coordination of resources, and relevant
      referrals. Appropriate documentation with a focus on Medicare reimbursement
      issues was included.

PMID- 9146249
TI  - Enhancing critical thinking with case studies and nursing process.
AB  - Challenged to enhance critical thinking concepts in a sophomore nursing process
      course, faculty expanded the lecture format to include group explorations of
      patient case studies. The group format facilitated a higher level of analysis of
      patient cases and more sophisticated applications of nursing process. This
      teaching strategy was a positive learning experience for students and faculty.

PMID- 9146251
TI  - Proposed 1998 federal budget abandons nurse education.

PMID- 9146252
TI  - Storytelling. An approach to client-centered care.
AB  - Storytelling as a communication technique influences listeners in a powerful way.
      The rebirth of storytelling, an old art form, is evident in nursing education
      programs. This approach enhances the learner's sensitivity to the illness
      experience. Stories relating to clinical situations use examples that address
      chronic illnesses, humanity, death, dying, and advance directives. Well-chosen
      stories have the ability to motivate, inspire, teach, or enhance the human
      sensitivity skills needed by interdisciplinary healthcare providers.

PMID- 9146253
TI  - Nursing students' experience bathing patients for the first time.
AB  - This study describes nursing students' experience bathing an adult patient for
      the first time. The students feared giving their first patient a bath and voiced
      concern about harming him or her. They discovered that it was easier when they
      were paired with another student and acknowledged being supported by fellow
      nursing students. Beginners were uncomfortable about exposing and touching the
      patient's private body parts and were surprised when patients helped them through
      the bath.

PMID- 9146254
TI  - Preparing advanced practice nurses for clinical decision making in specialty
      practice.
AB  - Dramatic changes in the delivery of healthcare have placed an increased emphasis
      on developing critical thinking skills and clinical decision making abilities of
      nurses on both the undergraduate and graduate levels. The authors discuss
      teaching-learning strategies that promote clinical decision making skills of
      advanced practice nurses. Particular attention is paid to advanced practice
      nurses who are being prepared to work within specialty practice settings. An
      algorithm to guide educators to teach clinical decision making is presented.

PMID- 9146255
TI  - What is the harm in imposing mandatory hospital nurse staffing regulations?
AB  - Efforts to establish mandated staffing ratios are shortsighted, and, though
      proponents may have the best intentions, many negative outcomes would flow from
      the public airing of this issue. The Institute of Medicine concluded in 1996 that
      there was insufficient quality outcome evidence to support the imposition of
      mandated nurse staffing ratios. The Massachusetts Nursing Association got
      legislation introduced in early 1996 which, if passed, would turn over to state
      lawmakers decisions governing nurse staffing in hospitals and other employment
      settings. There are high opportunity costs. Staffing regulations (if imposed)
      would force employers to ignore the dynamic interactions of economic, technology,
      capital, and labor supply variables, and thus needlessly impose the effect of
      increased labor costs on hospitals, taxpayers and nurses themselves. Chance for
      passage of this highly controversial legislation is unlikely, but the expenditure
      of political chips (and the loss of credibility) will increase the difficulty of
      obtaining a hearing from legislators the next time a nursing issue comes up.

PMID- 9146256
TI  - Organizational culture assessment before and after implementing patient-focused
      care.
AB  - Administration of a baseline multidisciplinary cultural assessment survey prior
      to any change effort (to evaluate as well as redesign units) is essential to
      success in any work redesign effort. Training efforts can then be directed toward
      effecting the desired changes in perceived norms and values. All involved groups
      should be surveyed using the same survey tool to elicit potential differences in
      perceptions of values among various work groups. Proactive values which are seen
      as predictive of greater change readiness include high teamwork (clan) values,
      flexibility, as shown by comfort with adhocracy, and recognition of external or
      market driven realities. Values and norms which are found to be problematic in
      change efforts include: a reactive orientation marked by strong hierarchical
      values, a command and control orientation, and strong reliance on rules.
      Predictors of success include a history of shared governance, while greater
      difficulties could be anticipated in both unionized and academic health care
      settings.

PMID- 9146257
TI  - Successful restructuring: maximizing training dollars.
AB  - Data regarding the cost of staff training associated with restructuring are
      scarce and incomplete, with little measurement of how staff performed after
      training. Effectiveness of staff education efforts are hampered by staff
      resistance to change, dysfunctional interdisciplinary team work, and existing
      system "glitches." The key criteria for successful education efforts related to
      restructuring are: development of measurable desired outcomes of training
      efforts, determination of solution appropriateness and resource needs, the
      thoughtful timing of interventions, and a high level of ongoing organizational
      support. Changes in teamwork effectiveness can be measured by examining variances
      in quality outcomes, timely and appropriate discharge planning, and resource cost
      measures such as use of overtime and absenteeism. Recommendations for effective
      use of training dollars include acknowledging resistance and providing forums
      which permit time (and a process) for re-education.

PMID- 9146258
TI  - Nurse/physician collaborative practice: improving health care quality while
      decreasing cost.
AB  - Significant variations and inconsistency in both the physician's and nurse's
      approach to the treatment of neonates with a "rule-out sepsis" (R/O sepsis)
      diagnosis is seen as both high cost and low quality. Because R/O sepsis is seen
      as a diagnostic dilemma for practicing clinicians, there has been a widespread
      tendency to readily initiate antibiotic treatment, without adequate consideration
      of the high financial and morbidity costs associated with the complications of
      treating the noninfected infant. This study demonstrates that the use of an
      agreed upon risk profile facilitated the collaborative standardization of
      diagnosis and treatment of the R/O sepsis patient, improved quality, and reduced
      costs (by minimizing over treatment) without increasing risk. This collaborative
      approach enhanced nurse-physician relationships, resulting in significant cost
      savings as well as diminished anxiety and confusion among the parents of neonates
      diagnosed with R/O sepsis.

PMID- 9146259
TI  - A cost-effectiveness analysis of neonatal nurse practitioners.
AB  - This retrospective study compares the cost and quality outcomes of two matched
      groups of infants; one of which received neonatal care provided by neonatal nurse
      practitioners (NNPs), the other delivered by the medical house staff in one
      hospital's NICU. Parameters evaluated for both groups included LOS, days on
      ventilator, days on oxygen, mortality, morbidity, and costs. The infants in the
      study were matched by place of birth, gestational age, birth weight, sex, race,
      and Apgar scores. This study showed that in the 35 cases cared for by NNPs, in
      collaboration with neonatoologists, neonates received care equal in quality to
      the 35 matched cases cared for by medical house staff at lower cost with greater
      continuity and consistency. Cost effectiveness of the NNP group was documented as
      $18,240 less per infant than those managed by medical house staff. Differences
      were seen as chiefly attributable to the NNP's unique blend of knowledge,
      communication skills, and continuous presence plus early identification of
      service coordination needs.

PMID- 9146260
TI  - Glue: the essence of leadership.

PMID- 9146261
TI  - Everybody wins!--nursing redesigns patient supplies.
AB  - Although initiated as a nursing team effort, positive results of the redesigned
      automated supply delivery, stocking, and charging process are filtering
      throughout the organization. The foresight in including non-caregivers in the
      team, the willing attitude of the members to look at the "big picture," and the
      outstanding attention to detail reflect well on the team spirit that is evident
      at St. Luke's Hospital.

PMID- 9146262
TI  - Nursing image: our public relations responsibility.

PMID- 9146263
TI  - The changing multidisciplinary team.

PMID- 9146264
TI  - Federal funding shapes nursing's future.

PMID- 9146265
TI  - The relationship between role conception and ethical behaviour of student nurses
      in Hong Kong.
AB  - This paper was designed to explore the relationships of three role conception
      types (the professional, bureaucratic and service role conceptions) to the
      ethical behaviour of student nurses from the apprenticeship and degree nursing
      programmes in Hong Kong. The effect of role discrepancy on ethical behaviour will
      also be explored. A nonprobability convenience sampling of 140 certificate
      students from a hospital-based training course and 81 degrees nursing students
      from a tertiary programme were selected. Role conception and role discrepancy
      were measured by the modified Nursing Role Conception scale originally developed
      by Corwin. For ethical behaviour, the Judgement About Nursing Decisions scale
      developed by Ketefian was used. Multiple regression analyses showed that the
      ideal professional role conception was a significant predictor, accounting for
      17% of the variance in the ideal ethical score of the degree students. Actual
      service role conception was a better predictor of the actual ethical score,
      explaining 10% and 14% of its variance for the certificate and degree students
      respectively. Professional and bureaucratic role discrepancies together were
      found to have a negative effect on the actual ethical behaviour of the degree
      students. These results suggest that professional values that have been developed
      through socialization in nurse education programmes could benefit patients only
      when degree students, in particular, could adapt successfully to the demands of
      bureaucratic organization.

PMID- 9146266
TI  - Immoral behaviour in medicine.
AB  - The purpose of this paper is to emphasize a social phenomenon that exists in
      Israel: immoral medicine. In recent years, nurses have been exposed to many
      instances of immoral medicine in hospitals. We want to protest about the demands
      for money from patients who are waiting for surgical intervention, arouse the
      medical community's conscience concerning these immoral activities, and improve
      professional and moral behaviour.

PMID- 9146267
TI  - Retired registered nurses' stories about being in ethically difficult care
      situations.
AB  - Twelve retired nurses were asked to narrate a care situation in which it had been
      difficult for them as nurses to know what was the right and good thing to do. The
      transcribed interviews were examined by content analyses. Physicians were the
      central coactors in the nurses' stories. Colleagues were seldom mentioned. Other
      ward staff were mainly called "the girls". The patient was central and referred
      to with respect. All the nurses focused on experiential learning. Guiding ethical
      principles are listed.

PMID- 9146268
TI  - Reflective practice: nursing ethics through story telling.
AB  - Reflection is a method of learning and teaching professional maturity through the
      critical analysis of experience. An illuminative research approach was used over
      a period of five years in collaboration with students on a palliative care course
      to investigate the effects of learning moral and ethical reasoning by reliving
      clinical experiences through story telling. This study concludes that: self
      concept is enhanced; communication skills are increased; and insight development
      is part of learning to reason fairly and ethically, and is achieved through a
      cathartic process, leading to the conceptualization and discovery of theories of
      nursing through reflective practice.

PMID- 9146269
TI  - Compromise and its limits.
AB  - Compromise as a notion is frequently met in discussion and debate regarding many
      everyday decisions, including health care. It therefore seems that it may be of
      interest and value to try to give this some careful consideration. In the
      following pages, an attempt is made to discuss what one might mean when one uses
      this concept. Consideration is then given to some possible uses of compromise is
      health care. Having suggested that in certain situations compromise is a morally
      valuable process, the author also considers some of the possible limits of
      compromise.

PMID- 9146270
TI  - Moving pragmatically beyond nature versus nurture: a personal perspective.

PMID- 9146271
TI  - An ethical dilemma in the highlands of Papua New Guinea.

PMID- 9146272
TI  - Qualitative research: is it becoming a new orthodoxy?

PMID- 9146273
TI  - Cutting edges: deconstructive inquiry and the mission of the border ethnographer.
AB  - Research is an activity nursing 'cannot not want'. Such an imperative compels me
      to sketch out some theoretical borders of a hybrid postmodern methodological
      framework that I have called 'border' ethnography. It is a methodology suspended
      between a still authoritative modernity and an as yet only partially legitimate
      postmodernity. At one level this position is somewhat uncomfortably in a post
      methodological terrain. The text that issues from such a tension-laden research
      space is, I argue, intensely autobiographical, inescapably ethnographic and
      inherently deconstructive. Ethno(autobio) graphy is a method 'on the run'; it
      destabilizes while it authorizes, it represents while it misrepresents, and it
      threatens to disintegrate as it comes into view. But, most importantly, it is the
      creature of a praxis-oriented endeavour not only to better understand a culture,
      but to actively intervene in its (re) production.

PMID- 9146274
TI  - Sairey Gamp: generating fact from fiction.
AB  - Australian midwives today are generally employed by maternity hospitals as
      obstetric or maternity nurses and specialize in only one area of the
      childbirthing process, under the umbrella of medicine. This is quite different to
      the provision of midwifery care in the nineteenth and early twentieth centuries
      in Australia, when childbirthing took place within a home setting, with a
      community midwife in attendance under the umbrella of the household. Australian
      midwives are now attempting to regain some of the autonomy that they believe was
      possessed by midwives of the past by being professionally accredited to operate
      as independent midwives. The de-institutionalization of childbirthing cannot
      simply come about by giving midwives accreditation to operate as autonomous
      practitioners, as the forces that led society to institutionalize childbirthing
      practices, as well as the avenues for change, are complex. This paper examines
      one of the forces behind that change: the denigration of the image of the
      community midwife by the medical and nursing professions, through the character
      of Sairey Gamp created by Charles Dickens. By examining the historical terrain
      and the historical influences that led to the demise of the community midwife, we
      can provide answers for debate on the present status of the midwife.

PMID- 9146275
TI  - Big battles for small gains: a cautionary note for teaching reflective processes
      in nursing and midwifery practice.
AB  - Since 1988, Australian university nursing courses have adopted the processes of
      educationalists in embracing reflective practitioner concepts and strategies. The
      assumption underlying reflective practice appears uniformly to be that if
      practitioners reflect on and in their practice worlds they can develop ways of
      changing them. This paper will outline some cautionary points in teaching
      reflective processes for use in nursing practice, given that they have been
      processes intent on mobilizing change in densely impacted hegemonic structures in
      healthcare organizations. To demonstrate that the limits of reflective practice
      may constitute big battles for small gains, a research project undertaken with
      practising midwives will be used as a case in point.

PMID- 9146276
TI  - Postmodern feminist emancipatory research: is it an oxymoron?
AB  - Many nurse-researchers who use feminist methods believe that postmodernism
      undermines the scientific and emancipatory aspirations of our discipline and they
      are therefore wary of postmodern theories. One of the main threats of
      postmodernism is the critique of humanism because humanism forms the ethical
      foundation for both nursing and feminism. These critiques expose the dark
      underside of humanistic ideals and show how, paradoxically, humanism has
      functioned to oppress people. The arguments presented here help emancipatory
      researchers to defend their practices, both in relation to research participants
      and in the ways in which the subjects is theorized. The conclusion is that
      postmodernism can be compatible with politically motivated, humanistically-based
      inquiry.

PMID- 9146277
TI  - The nurse educator as teacher: exploring the construction of the 'reluctant
      instructor'.
AB  - This paper explores the discursive construction of the category of teacher
      identified as the 'reluctant instructor'. Data are drawn from my doctoral study,
      an ethnography of a school of nursing located in the higher education sector in
      which I was employed. This study explored the question: What shapes nurse
      educators and what do they, in turn, shape? Participants included nurse educators
      who taught a pre-registration programme. Data were gathered through interview and
      observations of classroom teaching. Analysis focused on the discursive
      constitution of participants' sense of being a nurse educator and on the
      implications of their ways of 'knowing and doing' for students. The analysis
      suggests that the dominant subject positions adopted by participants were those
      of 'academic' and 'victim'. They employed an ideal/real dichotomy to give a sense
      of coherence to the inconsistencies or contradications that they saw as
      structuring their daily activities. Being an academic entailed being an educator,
      specifically a facilitator, as being competent and having some degree of
      autonomy. However, participants saw the reality of their situation as markedly
      different from their ideal; as exhibiting traits of the 'outmoded', oppressive,
      hospital system of nurse training. Within this context most participants
      positioned themselves as a 'reluctant instructor'. The implications of their
      practices for the creation of the 'passive student' are suggested in the paper.
      In this analysis the nurse educator is viewed as implicated in the formation and
      maintenance of the context in which she or he is located. Such a view challenges
      the neutrality that is implicated in understandings of the nurse educator that
      inform nursing texts and that helped constitute participants' sense of self.

PMID- 9146278
TI  - Phenomenography: an alternative approach to researching the clinical decision
      making of nurses.
AB  - In this paper, the limitations associated with current research approaches to the
      study of clinical decision-making are discussed. Research examining the clinical
      decision-making of nurses and doctors, and associated work in information
      procession, is reviewed. It is concluded that although the research is valuable
      in furthering the understanding of clinical decision-making, there are
      limitations associated with the current research approaches. The limitations are
      primarily related to the research approaches employed and the concentration on
      experienced nurses. The research fails to examine the development of clinical
      decision-making ability and the learning that occurs in practice. Phenomenography
      is proposed as an alternative approach. The aim of phenomenography is to describe
      an individual's perception of a phenomenon. Phenomenography is relevant to the
      study of clinical decision-making as it is concerned with variation in
      experience. When applied to the study of new graduate nurses, phenomenography can
      provide valuable information in relation to individual differences in learning
      that arise from experience, what factors influence learning and how they affect
      clinical decision-making ability.

PMID- 9146279
TI  - The (im)possibilities of poststructuralist and critical social nursing inquiry.
AB  - Methodologies of poststructuralist theory and critical social theory may be
      appropriated for nursing research and practice. Researchers using either
      methodology employ an analysis of power to explore experiences in various fields,
      and raise issues that are highly relevant to nursing. However, the two
      methodologies differ and, often, the respective theories are sharply opposed. In
      this paper, the differences both from within and between each approach are
      explored, showing their tensions and limits. I contend that a reflexive approach
      to discourse analysis provides insight into some of the methodological challenges
      that arise in the context of both theories. It is argued that the differences
      between poststructuralism and critical social theory seem likely to be mellowed
      by encounters that treat each other with respect. To some extent, such encounters
      may tend to converge the two positions.

PMID- 9146280
TI  - Heideggerian phenomenology: an approach to understanding family caring for an
      older relative.
AB  - Recent research has found that family caregivers do not discuss their caregiving
      in terms of tasks but instead describe their care as shaped by concerns,
      commitments and goals. The purpose of this paper is to challenge the ways in
      which nurses approach the family caregiving process and to explore possibilities
      for evolving nursing knowledge by questioning existing practice in the light of
      developing insight into the ways in which being a family caregiver is meaningful.
      A critique of the philosophical orientations of rationalism and empiricism
      provides a platform to discuss the merits of a Heideggerian phenomenological
      approach in assisting nurses to better understand family caring experience. Such
      critique serves to support the notion of displacing the traditional scientific
      view as the prime means of disclosing truth, acknowledging alternative ways of
      knowing.

PMID- 9146281
TI  - Jane Robinson in a conversation with Judith Parker.

PMID- 9146283
TI  - Nursing, pain and pain management.

PMID- 9146282
TI  - Thoughts of a wet mind in a dry season: the rhetoric and ideology of psychiatric
      nursing.

PMID- 9146284
TI  - Discussions about shorter shifts miss the point.

PMID- 9146285
TI  - Liberal sentiments. Interview by David Payne.

PMID- 9146286
TI  - Continental drift.

PMID- 9146287
TI  - The voices of reason.

PMID- 9146288
TI  - Ready to answer a different call. Interview by Daloni Carlisle.

PMID- 9146289
TI  - Lend me your ears.

PMID- 9146290
TI  - Night ride.

PMID- 9146291
TI  - Blues in the night.

PMID- 9146292
TI  - Out of the shadows.

PMID- 9146293
TI  - Prisoners of pain.

PMID- 9146294
TI  - Under siege.

PMID- 9146295
TI  - Intravenous therapy at home.

PMID- 9146296
TI  - Music and movement to exercise older people.
AB  - While life expectancy is increasing, research suggests that there has not been a
      corresponding improvement in health in older age. This article considers the role
      of exercise in promoting healthy ageing and describes a nurse-led exercise
      programme for older people.

PMID- 9146297
TI  - The importance of good record-keeping.
AB  - When large numbers of health care staff from different professional groups are
      involved in the care of individual clients, the need for simple, understandable,
      uniform casenotes becomes paramount. This article describes how a survey of the
      different casenotes used by various CPN teams led to the devising of a new
      system. The aim was to encourage good practice and develop a standardised record
      keeping system.

PMID- 9146298
TI  - Measurement of cholesterol and triglyceride.
AB  - As part of a continuing series on how the work of pathology laboratories
      contribution to patient care, this article looks at the measurement of the
      concentration of cholesterol and triglyceride in blood. The normal physiological
      function of cholesterol and triglyceride is described and blood sampling
      precautions explained. Finally, the causes and clinical consequences of
      abnormally raised levels are discussed.

PMID- 9146299
TI  - Health care for women with learning disabilities.
AB  - This article describes a research project exploring the basic health education ow
      women with learning disabilities. It demonstrated that preventive and well-woman
      needs were not being met. In response a joint venture was developed between a
      community learning disabilities team and local well woman and family planning
      services. The article describes how an informal and accessible clinic was
      established for women with learning disabilities.

PMID- 9146300
TI  - Rheumatology. The role of the nurse.

PMID- 9146302
TI  - Use it or lose it.

PMID- 9146301
TI  - Floor plan.

PMID- 9146303
TI  - Finding the flaw.
AB  - EDUCATION: midwives, practice nurses, health visitors and school nurses can
      provide health education which is essential in preventing incontinence. Minority
      ethnic groups must not be forgotten--leaflets are available in a variety of
      languages. ASSESSMENT: only by identifying the type and cause of incontinence can
      appropriate treatment and management be decided. Practice nurses and health
      visitors can be involved in assessment. REFERRAL: if more than occasional light
      incontinence is identified or the practice nurse or health visitor does not feel
      competent to deal with the problem, women must be encouraged to seek further help
      and should be referred to their GP or local continence advisory service, which
      usually takes self-referrals.

PMID- 9146304
TI  - Foreign policy.

PMID- 9146305
TI  - Discontinuing the LVAD: ethical considerations.

PMID- 9146306
TI  - Who should undergo esophagectomy?

PMID- 9146307
TI  - Impact of size mismatch and left ventricular function on performance of the St.
      Jude disc valve after aortic valve replacement.
AB  - BACKGROUND: The hemodynamic function of the St. Jude valve may change relative to
      changes in left ventricular function after aortic valve replacement for aortic
      stenosis. From theoretical reasons one may hypothesize that prosthetic valve
      hemodynamic function is related to left ventricular failure and mismatch between
      valve size and patient/ventricular chamber size. METHODS: Forty patients aged 24
      to 82 years who survived aortic valve replacement for aortic stenosis with a
      standard St. Jude disc valve (mean size, 23.5 mm; range, 19 to 29 mm) were
      followed up prospectively with Doppler echocardiography and radionuclide left
      ventriculography preoperatively and 9 days, 3 months, and 18 months after the
      operation with assessment of intravascular hemolysis at 18 months. Follow-up to a
      maximum of 7.4 years (mean, 6.3 years) was 100% complete. RESULTS: Left
      ventricular muscle mass index decreased from 198 +/- 62 g.m-2 preoperatively to
      153 +/- 53 g.m-2 at 18 months (p < 0.001), paralleled by a significant increase
      in left ventricular ejection fraction, peak ejection rate, and peak filling rate;
      only 18% of the patients had normal left ventricular muscle mass index and only
      32% normal ventricular function (normal left ventricular ejection fraction, peak
      ejection rate, peak filling rate, early filling fraction, and late filling
      fraction during atrial contraction) at 18 months. Prosthetic valve peak Doppler
      gradient dropped from 20 +/- 6 mm Hg at 9 days to 17 +/- 5 mm Hg at 18 months (p
      < 0.05). Reduction of left ventricular muscle mass index was unrelated to peak
      gradient and size of the valve. Peak gradient at 18 months rose with valve
      orifice diameter of 17 mm or less (by 6 mm Hg), orifice diameter/body surface
      area of 9 mm.m-2 or less (by 5 mm Hg), left ventricular enddiastolic dimension
      (by 23 mm Hg per 10 mm increase), and impaired ventricular function (by 3 mm Hg).
      All but 2 patients (5%) had intravascular hemolysis; none had anemia. Two
      patients with moderate paravalvular leak had the highest serum lactic
      dehydrogenase levels; 4 patients with trivial leak had higher serum lactic
      dehydrogenase levels than those without leak. Serum lactic dehydrogenase levels
      rose with moderate paravalvular leak, impaired ventricular function, and valve
      orifice diameter. Six patients with trivial or moderate paravalvular leak had a
      cumulative 7-year freedom from bleeding and thromboembolism of 44% +/- 22%
      compared with 87% +/- 5% for those without leak (p < 0.05). CONCLUSIONS: The peak
      gradient of the St. Jude aortic valve dropped marginally over the first 18
      postoperative months in association with incomplete left ventricular hypertrophy
      regression and marginal improvement of ventricular function. Mismatch between
      valve size and ventricular cavity size or patient size and impaired function of a
      dilated ventricle significantly compromised the performance of the St. Jude
      valve. Probably explained by platelet destruction or activation, paravalvular
      leak was related to bleeding and thromboembolic complications.

PMID- 9146308
TI  - Coronary artery fistulas in infants and children: a surgical review and
      discussion of coil embolization.
AB  - BACKGROUND: Coronary artery fistula (CAF) is a rare congenital anomaly that can
      be complicated by intracardiac shunts, endocarditis, myocardial infarction, or
      coronary aneurysms. Recent reports have emphasized the efficacy of percutaneous
      transcatheter techniques. The purpose of this article is to review a 28-year
      surgical experience with CAF as a standard for comparison and to discuss the
      emergence and efficacy of transcutaneous catheter coil embolization as an
      alternative form of therapy. METHODS: From 1968 to 1996, 17 patients (age, 6
      weeks to 16.5 years; mean age, 5.5 years) were diagnosed with CAF: 8 of 12 by
      echocardiography and 17 of 17 by cardiac catheterization. All patients with
      isolated CAF (n = 13) were asymptomatic despite significant clinical,
      electrocardiographic, and chest roentgenographic findings in 10. Sixteen had
      congenital CAF and 1 had acquired CAF after tetralogy of Fallot repair with
      injury of the anomalous left anterior descending coronary artery. Associated
      anomalies included tetralogy of Fallot (2), atrial septal defect (1), and patent
      ductus arteriosus (1). Nine fistulas originated from the right coronary artery
      and eight from the left. Drainage was to the right ventricle (9), right atrium
      (4), pulmonary artery (3), and left atrium (1). RESULTS: All patients had a
      median sternotomy with epicardial or endocardial ligation. Cardiopulmonary bypass
      was used in 8; 1 of these (iatrogenic CAF) required distal internal mammary
      artery bypass graft. There were no operative or late deaths. Follow-up evaluation
      by physical examination (17), echocardiography (8), and catheterization (2)
      showed no evidence of recurrent or residual CAF. A retrospective review of the 16
      available cine cardioangiograms showed that coil embolization was possible in, at
      most, 6 patients. CONCLUSIONS: Early surgical management of CAF is a safe and
      effective treatment resulting in 100% survival and 100% closure rate.
      Transcatheter embolization is a reasonable alternative to standard surgical
      closure in only a very small, select group of patients. These surgical results
      should be considered the standard against which transcatheter techniques are
      compared.

PMID- 9146309
TI  - Regional blood flow during pulsatile cardiopulmonary bypass and after circulatory
      arrest in an infant model.
AB  - BACKGROUND: Pulsatile perfusion systems have been proposed as a means of
      improving end-organ perfusion during and after cardiopulmonary bypass. Few
      attempts have been made to study this issue in an infant model. METHODS: Neonatal
      piglets were subjected to nonpulsatile (n = 6) or pulsatile (n = 7)
      cardiopulmonary bypass and 60 minutes of circulatory arrest. Cerebral, renal, and
      myocardial blood flow measurements were obtained at baseline, on bypass before
      and after circulatory arrest, and after bypass. RESULTS: Cerebral blood flow did
      not differ between groups at any time and was diminished equally in both groups
      after circulatory arrest. Renal blood flow was diminished in both groups during
      bypass but was significantly better in the pulsatile group than in the
      nonpulsatile group prior to, but not after, circulatory arrest. Myocardial blood
      flow was maintained at or above baseline in the pulsatile group throughout the
      study, but in the nonpulsatile group, it was significantly lower than baseline
      during CPB prior to circulatory arrest and lower compared with baseline and with
      the pulsatile group 60 minutes after CPB. CONCLUSIONS: Pulsatile bypass does not
      improve recovery of cerebral blood flow after circulatory arrest, may improve
      renal perfusion during bypass but does not improve its recovery after ischemia,
      and may have beneficial effects on myocardial blood flow during bypass and after
      ischemia compared with nonpulsatile bypass in this infant model.

PMID- 9146310
TI  - Variable response to inhaled nitric oxide after cardiac surgery.
AB  - BACKGROUND: Inhaled nitric oxide (NO) is a promising therapy that may be valuable
      in the control of pulmonary hypertension in cardiac surgical patients. Patients
      with valvular heart disease have remodeling of the pulmonary vascular bed that
      contributes to pulmonary hypertension. The purpose of this study was to compare
      the efficacy of inhaled NO in cardiac surgical patients with pulmonary
      hypertension with and without valvular heart disease. METHODS: The effect of
      inhaled NO (40 ppm) on pulmonary hemodynamics in patients with pulmonary
      hypertension (mean pulmonary artery pressure > or = 30 mm Hg) was studied in the
      operating room after cardiac operation. Fifteen patients with valvular heart
      disease comprised the study group; 25 patients undergoing aortocoronary bypass
      grafting were controls. RESULTS: In patients undergoing aortocoronary bypass
      grafting, inhaled NO produced a 24% decrease in mean pulmonary artery pressure
      (33 +/- 1 to 25 +/- 1 mm Hg; p < 0.05), a 36% decrease in pulmonary vascular
      resistance (375 +/- 30 to 250 +/- 30 dyne.s.cm-5; p < 0.05), and no change in
      systemic arterial blood pressure. On the other hand, patients with pulmonary
      hypertension from valvular heart disease did not respond to inhaled NO: mean
      pulmonary artery pressure was 39 +/- 3 mm Hg and pulmonary vascular resistance
      was 620 +/- 30 dyne.s.cm-5 before, during, and after NO. CONCLUSIONS: Among
      cardiac surgical patients with pulmonary hypertension, the response to inhaled NO
      is variable. Despite the promise of inhaled NO as a pulmonary vasodilator in
      cardiac surgical patients, these data suggest that alternative therapies are
      needed to control pulmonary hypertension in patients with pulmonary hypertension
      from valvular heart disease.

PMID- 9146311
TI  - The internal mammary artery malperfusion syndrome: late angiographic
      verification.
AB  - BACKGROUND: Here we report our experience with the incidence and the surgical
      treatment of the internal mammary artery (IMA) malperfusion syndrome, evaluate
      the predictive role of previously described risk factors for the syndrome, and
      assess the late patency of IMA grafts in patients in whom an IMA malperfusion
      syndrome was diagnosed and treated by additional saphenous vein grafting of the
      left anterior descending coronary artery. METHODS: From June 1992 to November
      1995, 969 IMAs were anastomosed to the left anterior descending coronary artery
      system. In 11 patients, IMA malperfusion syndrome was diagnosed and treated by
      additional saphenous vein grafting of the LAD. There were 8 men and 3 women with
      a mean age of 58.9 years. The angiographic and clinical data for each patient
      were reviewed, and all but 1 surviving patient underwent late angiographic
      control (mean follow-up, 18 months; range, 4 to 46 months). RESULTS: One patient
      died in the hospital. No previously described risk factor was strongly associated
      with the occurrence of IMA malperfusion syndrome. Late angiography revealed a
      malfunctioning IMA graft in 7 of the 9 patients. A string sign was observed in 1
      patient and a normally functioning IMA anastomosed to a diagonal branch not
      connected to the LAD, in another. In no patient was a widely patent and normally
      functioning IMA graft observed. CONCLUSIONS: In our series, a high proportion of
      IMA grafts were found to be malfunctioning at late angiography. This observation,
      in contrast to previous reports, suggests that IMA malperfusion syndrome can
      often be attributable to technical problems in harvesting the IMA or in
      performing the IMA anastomosis. Functional IMA insufficiency seems to play only a
      marginal role in determining the IMA malperfusion syndrome.

PMID- 9146312
TI  - Determination of size of aortic emboli and embolic load during coronary artery
      bypass grafting.
AB  - BACKGROUND: Embolic signals have been detected within both the aortic lumen and
      the intracranial vasculature during coronary artery bypass grafting. Total
      numbers of these emboli have been reported. The present study examined the size
      of individual emboli and the total volume of embolization. METHODS: Using
      transesophageal echocardiography, we continuously monitored the aortic lumen of
      10 patients undergoing isolated coronary artery bypass grafting. We manually
      analyzed 720,000 individual echo frames over a 4-minute period after the release
      of aortic clamps to track and to calculate the volume of 657 individual
      particles. The embolic load for the entire procedure was calculated from mean
      volume based on analysis of 1,508 particles. We simultaneously monitored the
      middle cerebral artery using transcranial Doppler ultrasonography and compared
      numbers of emboli detected by the two techniques. RESULTS: Particle diameter
      ranged from 0.3 to 2.9 mm (mean, 0.8 mm), and particle volume from 0.01 to 12.5
      mm3 (mean, 0.8 mm3). Twenty-eight percent of particles measured 1 mm or more, 44%
      measured 0.6 to 1.0 mm, and only 27% measured 0.6 mm or less in diameter. Aortic
      embolic load for the procedure ranged from 0.6 cm3 to 11.2 cm3 (mean, 3.7 cm3).
      Estimated cerebral embolic load for the procedure ranged from 60 to 510 mm3
      (mean, 276 mm3). The fraction of aortic emboli entering the cerebral circulation
      was very variable (3.9% to 18.1%). Seventy-six percent of the embolic volume
      after the release of clamps occurred over a 20-second period. Only 1 patient was
      encephalopathic perioperatively. This patient had the largest estimated cerebral
      embolic load (510 mm3) and the second largest aortic embolic load (8.4 cm3).
      CONCLUSIONS: We determined the size of individual intraaortic embolic particles
      and the total volume of embolization during coronary artery bypass grafting, and
      found the proportion entering the cerebral circulation to be very variable. The
      constitution of these particles and the neurologic impairment resulting from such
      embolization remains to be determined.

PMID- 9146313
TI  - Normothermic retrograde blood cardioplegia with or without preceding ischemic
      preconditioning.
AB  - BACKGROUND: Preconditioning has been suggested as the most powerful mechanism of
      myocardial protection against prolonged ischemia. However, whether
      preconditioning offers additional benefits over cardioplegia during coronary
      artery bypass grafting is not known. METHODS: Thirty patients undergoing coronary
      artery bypass grafting were randomized into two groups. After aortic cross
      clamping, group 1 received antegrade blood and blood cardioplegia followed by
      normothermic retrograde blood cardioplegia (controls), whereas group 2 patients
      were subjected to 5 minutes of global ischemia followed by reperfusion with
      antegrade and retrograde blood cardioplegia (preconditioned). The transcardiac
      differences in oxygen saturation, pH, and lactate were measured during
      cardiopulmonary bypass. Myocardial biopsy specimens were taken from half of the
      patients for adenosine triphosphate determination. The extent of myocardial
      injury was estimated by monitoring the postoperative leakage of creatine kinase
      MB and troponin T. Immediate hemodynamic recovery and postoperative complications
      were also observed. RESULTS: The 5-minute preconditioning induced marked lactate
      and acid production, and myocardial adenosine triphosphate levels tended to
      decrease. The heart continued to produce lactate and acid during retrograde
      cardioplegia, but the transcardiac pH and lactate differences were similar in
      both groups. Adenosine triphosphate level measured at the end of the cross-clamp
      period was decreased to a half and one third of the preclamp values in the
      control and preconditioned groups, respectively. The postoperative creatine
      kinase-MB and troponin T effluxes tended to be more elevated in the
      preconditioned group, yet hemodynamic recovery and the number of postoperative
      complications were similar in both groups. CONCLUSIONS: The results show that a 5
      minute preconditioning ischemia does not offer any additional benefits over
      normothermic retrograde blood cardioplegia during coronary artery bypass
      grafting.

PMID- 9146314
TI  - Physiology, histology, and 2-week morphology of acute transmyocardial channels
      made with a CO2 laser.
AB  - BACKGROUND: Transmyocardial revascularization with a CO2 laser appears to improve
      symptoms in patients with refractory angina. However, it remains controversial as
      to whether blood flow through the channels is the mechanism of benefit,
      especially in the acute setting. METHODS AND RESULTS: Three protocols were used
      to test whether blood flows through transmyocardial CO2 laser revascularization
      channels. First, channels were made in excised, cross-perfused dog hearts (n = 5)
      using a CO2 laser (The Heart Laser; PLC Systems Inc, Milford, MA; 40 J/pulse)
      followed by ligation of the proximal left anterior descending coronary artery.
      Colored microspheres injected into the left ventricular chamber failed to detect
      any significant transmyocardial blood flow. In the second protocol (n = 4), laser
      channels were created in the left anterior descending artery territory, the left
      anterior descending artery was ligated, and the hearts were excised after 24
      hours. Triphenyltetrazolium chloride staining revealed that no viable myocardium
      was detected around the laser channels in the ischemic myocardium. Finally,
      channels examined 2 weeks after creation in normal (n = 6) or ischemic (n = 4)
      myocardium did not maintain their original caliber but were invaded by
      granulation tissue, which included a large amount of smaller vascular spaces and
      vessels of various sizes. CONCLUSIONS: Transmyocardial laser revascularization
      channels made with this CO2 laser did not provide acute myocardial perfusion or
      preserve myocardial viability in the face of acute ischemia. Channel morphology
      changes dramatically within the first 2 weeks. To the degree that these findings
      pertain to human myocardium, the results suggest that transmyocardial blood flow
      may not be the mechanism of benefit of this procedure, particularly in the acute
      setting.

PMID- 9146315
TI  - Simultaneous subclavian artery reconstruction in coronary artery bypass grafting.
AB  - BACKGROUND: Subclavian artery occlusive lesion, although rare, is sufficiently
      important to consider before coronary artery bypass grafting because it can cause
      not only symptoms of the lesion per se, but also the postoperative coronary
      subclavian steal phenomenon. METHODS: Four patients undergoing coronary artery
      bypass grafting received simultaneous reconstruction of the subclavian artery.
      During aortic cross-clamping, an 8-mm ring-reinforced polytetrafluoroethylene
      graft was attached to the aorta perpendicularly. The prosthetic graft was led to
      the proximal segment of the axillary artery through the second intercostal space
      and anastomosed to the inferior surface of the artery. RESULTS: Three patients
      received unilateral reconstruction of the subclavian artery, whereas another
      received bilateral reconstruction. There were no complications related to the
      subclavian reconstruction procedure. Post-operative angiograms revealed excellent
      patency of the prosthetic grafts. All of the patients have been asymptomatic with
      follow-up periods ranging from 9 to 50 months. CONCLUSIONS: To perform
      simultaneous subclavian artery reconstruction along with coronary artery bypass
      grafting, the aortoaxillary bypass procedure using an 8-mm
      polytetrafluoroethylene graft may be the method of choice because it has lower
      potential for complications and is less technically demanding.

PMID- 9146316
TI  - Cardiac enzymes and autotransfusion of shed mediastinal blood after myocardial
      revascularization.
AB  - BACKGROUND: Autotransfusion of shed mediastinal blood reduces blood requirement
      after coronary artery bypass grafting. Recently, two nonrandomized trials
      indicated that autotransfusion elevates the levels of cardiac enzymes after
      cardiac operations. METHODS: Prospective, randomized controlled studies involving
      120 patients (study A) and 15 patients (study B) having elective uncomplicated
      coronary artery bypass grafting were performed. Autotransfusion of shed
      mediastinal blood was performed for 18 hours in the patients allocated to
      autotransfusion. Serum levels of cardiac enzymes were measured. In study B
      cardiac enzyme levels in shed mediastinal blood and circulating blood were
      measured 1 hour postoperatively. RESULTS: Cardiac enzyme levels were
      significantly elevated in the patients receiving autotransfusion. In patients
      with a perioperative myocardial infarction. The level of creatine kinase-MB was
      much higher than in the autotransfused patients without myocardial infarction.
      The level of cardiac enzymes was higher in shed mediastinal blood compared with
      circulating blood. CONCLUSIONS: Postoperative autotransfusion of shed mediastinal
      blood causes elevation of cardiac enzyme levels after coronary artery bypass
      grafting.

PMID- 9146317
TI  - Myocardial edema: comparison of effects on filling volume and stiffness of the
      left ventricle in rats and pigs.
AB  - BACKGROUND: This study compared the adverse effects of crystalloid-induced
      myocardial edema on left ventricular (LV) compliance in small and large hearts.
      METHODS: Plegisol (289 mOsm/L) was perfused into the coronary arteries of pigs (n
      = 8) and 1:1 dilute Plegisol (145 mOsm/L) into the coronary arteries of rats (n =
      6). Pressure-volume relations, heart weight, and water content were then
      determined. The pressure-volume relations were compared using an LV volume at a
      pressure of 10 mm Hg. RESULTS: Edema in rats was associated with significant (p <
      0.05) increases in heart weight (1.1 +/- 0.0 g versus 1.4 +/- 0.1 g [average +/-
      standard error of the mean]) and water content (76.8% +/- 0.4% versus 81.3% +/-
      0.8%), but an increase in LV stiffness (7.91 +/- 0.52 versus 9.27 +/- 1.42) and a
      decrease in the LV volume at 10 mm Hg (0.25 +/- 0.02 mL versus 0.14 +/- 0.05 mL)
      were not statistically significant. Edema in pigs was associated with
      statistically significant (p < 0.05) increases in LV stiffness beta (0.050 +/-
      0.004 versus 0.072 +/- 0.008), heart weight (207 +/- 8 g versus 274 +/- 9 g), and
      water content (79.8% +/- 0.6% versus 85.3% +/- 0.6%) and a significant decrease
      in the LV volume at 10 mm Hg (88.4 +/- 5.8 mL versus 60.4 +/- 6.8 mL).
      CONCLUSIONS: Myocardial edema is associated with an increase in water content and
      LV stiffness and a decrease in the LV volume at 10 mm Hg in both species. In
      rats, however, the water content is smaller in the control state and a more
      hypotonic perfusate is needed to induce a given degree of edema.

PMID- 9146318
TI  - Preoperative ECMO in congenital cyanotic heart disease using the AREC system.
AB  - BACKGROUND: In cyanotic congenital heart disease, oxygen delivery is impaired
      either by reduced pulmonary perfusion or by limited entry of oxygenated blood
      into the systemic circulation. Additional impairment of oxygen delivery (eg, in
      pulmonary hypertension) leads to hypoxic cerebral damage. Preoperative
      extracorporeal membrane oxygenation enables oxygenation in otherwise untreatable
      cases. METHODS: In 3 neonates suffering from cyanotic congenital heart disease (1
      with tricuspid atresia and 2 with transposition of the great arteries) with
      arterial desaturation despite application of prostaglandins, balloon
      atrioseptostomy, and eventually inhaled nitric oxide during intermittent positive
      pressure ventilation with an inspired oxygen fraction of 1, oxygenation could
      only be established by means of preoperative extracorporeal membrane oxygenation.
      We used a venovenous single-lumen cannula tidal-flow extracorporeal membrane
      oxygenation system described by Chevalier and associates that has previously been
      used for extracorporeal lung support. In this system, called AREC (assistence
      respiratoire extra-corporelle), alternating clamps and a nonocclusive roller pump
      were used. RESULTS: All 3 survived. CONCLUSIONS: We conclude that the AREC system
      enables sufficient preoperative oxygenation in patients with cyanotic congenital
      heart disease and hypoxia in spite of all conventional therapeutic means. This
      provides a stable preoperative condition for elective palliation or correction.

PMID- 9146319
TI  - Cardioplegia preserves hypoxic response in isolated coronary arteries but not in
      isolated hearts.
AB  - BACKGROUND: Experiments were designed to determine whether hyperkalemic
      crystalloid cardioplegic solution alters the hypoxic response of isolated
      segments of rabbit coronary arteries. METHODS: Coronary arteries were suspended
      in organ chambers to measure isometric force. We measured the coronary perfusion
      pressure at a constant flow rate in isolated Langendorff-perfused hearts.
      Coronary arteries and hearts were preserved in warm (37 degrees C) physiologic
      solution or in cold (10 degrees C) crystalloid cardioplegic solution. RESULTS: In
      all groups of coronary arteries, the acetylcholine-induced relaxation before and
      after preservation was unchanged (n = 7). Hypoxia (15 mm Hg) caused an
      endothelium-dependent contraction, the amplitude of which did not change after
      cardioplegia. Conversely, in coronary arteries preserved in physiologic solution,
      hypoxic contraction amplitude decreased by 67% +/- 17%. In isolated hearts,
      hypoxic perfusion (15 mm Hg) induced a vasodilation. In all groups, the second
      hypoxic vasodilation was significantly greater (group 1, first hypoxic perfusion
      2.8% +/- 2.8%, second hypoxic perfusion 18.2% +/- 7.1%; group 2, first hypoxic
      perfusion 6.8% +/- 1.5%, second hypoxic perfusion 29% +/- 9%). CONCLUSIONS: The
      crystalloid cardioplegic solution did not change the hypoxic response in isolated
      hearts and preserved the endothelium-dependent hypoxic contraction in coronary
      arteries.

PMID- 9146320
TI  - Risks of cardiac operations for elderly patients: reduction of the age factor.
AB  - BACKGROUND: Age has been considered an important risk factor for cardiac
      operations. Recent refinements have been designed to reduce cardiac, neurologic,
      and renal complications. METHODS: Analysis of cardiac surgical outcomes including
      mortality, length of stay, complications, and costs were undertaken for a
      consecutive series of 285 patients 70 years old and older and 568 patients
      younger than 70 years who underwent operation during 1991 through 1995.
      Management included antegrade and retrograde cold and warm blood cardioplegia,
      epicardial echocardiography, retrosternal dissection for reoperations,
      maintenance of "normal" arterial pressure, and measures to avoid renal
      dysfunction. Parsonnet risk stratification and multiple regression were used to
      account for risk factors. RESULTS: The 30-day mortality rate for elderly patients
      was 1.8% (5/285) and 1.8% (10/568) for patients less than 70 years old (p = not
      significant). The hospital mortality rate for the elderly patients was 3.2%
      (9/285) versus 2.5% (14/568) for the younger group (p = not significant). The
      frequencies of complications were not different. Over the 5-year period, length
      of stay decreased from 12.5 +/- 1.5 days to 8.9 +/- 0.9 days for patients 70
      years old and older and from 11.5 +/- 0.1 to 6.4 +/- 0.3 days for patients less
      than 70 years old. Hospital charges for the elderly group were 13% higher.
      CONCLUSIONS: Modern cardiac surgical techniques and clinical practices have
      reduced the importance of the age factor.

PMID- 9146321
TI  - Effect of spinal cord preconditioning on paraplegia during cross-clamping of the
      thoracic aorta.
AB  - BACKGROUND: Paraplegia is a devastating complication of operations for thoracic
      or thoracoabdominal aneurysms. Preconditioning the brain with sublethal ischemia
      induces resistance to subsequent ordinarily lethal ischemia (ischemic tolerance).
      We investigated whether ischemic tolerance could be induced by preconditioning
      canine spinal cord. The role of heat-shock proteins (HSP) in this process was
      investigated. METHODS: In experiment 1, the preconditioning group (n = 6) had
      aortic cross-clamping for 20 minutes, whereas controls (n = 6) had no cross
      clamping. After 48 hours the aorta was cross-clamped for 60 minutes in both
      groups. Neurologic examination was performed 24 hours later and the spinal cord
      was studied for immunohistochemically. In experiment 2, either 48 hours after 20
      minutes of clamping or after sham operation (n = 4), HSP were investigated
      immunohistochemically. RESULTS: In experiment 1, 3 of 6 controls became
      paraplegic but none of the 6 preconditioning group dogs became paraplegic. The
      HSP appeared on sections from all 6 PC dogs and 3 control dogs that did not
      exhibit paraplegia. In experiment 2, HSP were present in clamped animals but
      could not be detected after sham operation. CONCLUSIONS: Ischemic tolerance was
      induced by preconditioning the canine spinal cord, in which HSP are believed to
      be involved.

PMID- 9146322
TI  - Bidirectional inferior vena cava-pulmonary artery shunt.
AB  - BACKGROUND: Bidirectional superior vena cava-pulmonary shunt is widely used as an
      interim palliation for patients with univentricular hearts. Bidirectional
      inferior vena cava-pulmonary artery shunt, as an alternative approach of partial
      Fontan circulation, may offer the advantage of performing the complete Fontan
      circulation more easily due to the already constructed inferior vena cava lateral
      tunnel. METHODS: We used bidirectional inferior vena cava-pulmonary artery shunt
      in 2 patients. Contraindications to a complete Fontan circulation were due to,
      respectively, a volume-overloaded systemic ventricle and an irregular pulmonary
      arterial tree. RESULTS: Postoperative courses were uneventful. There were no
      significant pleural effusions. Transcutaneous oxygen saturations were 77% and
      78%. Pulmonary-to-systemic blood flow ratios were 0.57 and 0.63. A complete
      Fontan circulation was safely performed 8 and 12 months later, without any
      "Fontan-related" complications. CONCLUSIONS: Bidirectional inferior vena cava
      pulmonary artery shunt can be useful in selected patients with univentricular
      hearts, although its place in the field of "partial Fontan operations" cannot be
      determined as yet.

PMID- 9146324
TI  - Extracorporeal membrane oxygenation using a centrifugal pump and a servo
      regulator to prevent negative inlet pressure.
AB  - BACKGROUND: We studied whether negative inlet pressure created by a centrifugal
      pump during extracorporeal membrane oxygenation damages blood. METHODS: Fresh,
      whole human blood and primer were circulated through a test circuit, applying an
      inlet pressure of 0, -50, or -100 mm Hg. Thereafter, hemolysis and kidney
      function were compared between 6 patients treated before and 14 patients treated
      after inclusion in our setup of extracorporeal membrane oxygenation with a servo
      inlet pressure regulator. RESULTS: In vitro, negative inlet pressure caused
      substantial hemolysis, leukocyte and platelet destruction, and complement
      activation. Maximal plasma free hemoglobin concentrations were 199 mg/100 mL
      before use of the servo inlet pressure regulator and 40 mg/100 mL afterward (p =
      0.06), and serum creatinine peaked at 330 and 115 mumol/L, respectively (p =
      0.03). The minimal 24-hour diuresis normalized for weight was 4.8 mL/kg before
      use of the servo inlet pressure regulator and 45.6 mL/kg afterward (p = 0.03).
      Three of 5 evaluable patients before use of the servo inlet pressure regulator
      and 1 of 14 patients after inclusion in this setup experienced anuria (p = 0.04).
      CONCLUSIONS: There were strong indications that reduction of negative pump inlet
      pressure with the servo regulator prevented hemolysis and kidney damage.

PMID- 9146323
TI  - Perfluorocarbon emulsion in the cardiopulmonary bypass prime reduces neurologic
      injury.
AB  - BACKGROUND: Perfluorocarbon emulsion has proved beneficial in the prevention and
      amelioration of experimental air embolism. We examined whether the addition of
      perfluorocarbon to the prime solution could lead to a reduction in the incidence
      and severity of neurologic injury after the formation of a massive air embolism
      during cardiopulmonary bypass. METHODS: Fourteen pigs underwent bypass in which
      either a crystalloid prime solution or a perfluorocarbon prime solution (10
      mL/kg) was used. Ten minutes into bypass a bolus (5 mL/kg) of air or saline
      (control) was delivered via the carotid artery. The resulting cerebral infarcts
      were graded on the basis of the findings in triphenyltetrazolium chloride-stained
      cerebral sections. Colored microspheres were used to measure cerebral blood flow.
      Bitemporal electroencephalography was used to evaluate cerebral function.
      RESULTS: Cerebral infarction was not found in the perfluorocarbon-air group (0 to
      5 animals), as compared with its occurrence in 3 of the 5 animals in the
      crystalloid-air group. Cerebral blood flow was also maintained or increased in
      the perfluorocarbon-air group (p < 0.05), and the electroencephalogram total
      power showed less of a decrease and recovered more completely (p < 0.05) than it
      did in the crystalloid-air group. CONCLUSIONS: The addition of perfluorocarbon
      emulsion to the cardiopulmonary bypass prime solution leads to a reduction in the
      incidence and severity of neurologic injury after the formation of a massive air
      embolism during bypass.

PMID- 9146325
TI  - Midterm results of mitral valve repair with the Sculptor annuloplasty ring.
AB  - BACKGROUND: The partly flexible Sculptor ring is more physiologic than the rigid
      Carpentier-Edwards ring and may improve outcome. METHODS: We studied 221
      consecutive patients who underwent mitral valve repair for mitral regurgitation.
      The Sculptor ring was randomly implanted in 30 patients (Sculptor ring group) and
      the Carpentier-Edwards ring in 36 patients (Carpentier-Edwards ring control
      group) from 1993 to 1994. Before 1993, 155 patients received the Carpentier
      Edwards ring (Carpentier-Edwards ring historical group). Baseline group
      characteristics were similar. RESULTS: Thirty-day mortality in the Sculptor ring,
      Carpentier-Edwards ring control, and Carpentier-Edwards ring historical groups
      was 0.0% versus 2.8% versus 3.2% (p = 0.61), respectively. At 18 months, survival
      was 86% +/- 6% versus 88% +/- 7% versus 90% +/- 3% (p = 0.89), and freedom from
      complications was 100% +/- 0% versus 100% +/- 0% versus 98% +/- 1% (p = 0.51) for
      endocarditis, 90% +/- 6% versus 94% +/- 4% versus 96% +/- 2% (p = 0.47) for
      severe mitral regurgitation, 93% +/- 5% versus 91% +/- 5% versus 92% +/- 2% (p =
      0.91) for thromboembolism, and 77% +/- 8% versus 80% +/- 7% versus 82% +/- 3% (p
      = 0.49) for myocardial failure, respectively. CONCLUSIONS: The Sculptor ring is a
      safe alternative to the prosthetic annuloplasty rings in current use. The
      benefits of its physiologic design are either clinically insignificant or
      undetectable with a small sample size.

PMID- 9146326
TI  - Radial artery has higher receptor-mediated contractility but similar endothelial
      function compared with mammary artery.
AB  - BACKGROUND: The radial artery (RA) has been used as an alternative arterial graft
      for coronary artery bypass grafting, but this artery has been suggested to be
      spastic. Endothelin-1 (ET) and angiotensin II (AII) have been measured with
      increased plasma concentrations during cardiopulmonary bypass. However, whether
      RA is reactive to these two important receptor-mediated vasoconstrictors is
      unknown. Also unknown is the endothelial function of this arterial conduit. This
      study was designed to compare RA and the internal mammary artery regarding the
      contractile characteristics to ET-1 and AII and endothelial function. METHODS:
      Ring segments of the RA and internal mammary artery taken from patients
      undergoing coronary artery bypass grafting were studied in organ chambers at a
      physiologic pressure. The contractility was determined from the contraction
      induced by ET-1 and AII as contraction force and the force normalized by
      circumference (g/mm). The endothelium-dependent relaxation was induced by the
      calcium ionophore A23187, a nonreceptor agonist, and substance P, a receptor
      agonist for endothelium-derived relaxing factors. Nitroglycerin was used to study
      the endothelium-independent relaxation. RESULTS: Both ET-1 and AII induced a
      higher contraction force (9.0 +/- 0.9 g, n = 12, versus 4.5 +/- 0.4 g, n = 38, p
      < 0.0001 for ET and 6.5 +/- 1.9 g, n = 7, versus 1.7 +/- 0.3 g, n = 8, p = 0.015
      for AII) and normalized force (0.95 +/- 0.1 g/mm versus 0.66 +/- 0.05 g/mm, p =
      0.007 for ET-1 and 0.8 +/- 0.2 g/mm versus 0.2 +/- 0.05 g/mm, p < 0.01 for AII)
      in RA than in the internal mammary artery. There were no significant differences
      detected between these arteries with regard to either endothelium-dependent (to
      substance P and A23187) or endothelium-independent (to nitroglycerin) relaxation
      (p > 0.05). CONCLUSIONS: We conclude that the human RA has a higher receptor
      mediated contractility (to ET-1 and AII) but similar endothelial function
      compared to the internal mammary artery. The study reveals the nature of the more
      spastic characteristics of the RA, supports the necessity of a more active
      pharmacologic intervention to relieve spasm in the RA, and suggests that the
      similar endothelium-derived relaxing factor-mediated endothelial function of the
      RA compared with the internal mammary artery may be the basis for a satisfactory
      long-term patency.

PMID- 9146328
TI  - Endothelin-1 and neutrophil activation during heparin-coated cardiopulmonary
      bypass.
AB  - BACKGROUND: Heparin-coated circuits attenuate the systemic inflammatory response
      to cardiopulmonary bypass. The present study compares two different heparin
      coatings in terms of the release of endothelin-1 and neutrophil glycoproteins.
      METHODS: Forty low-risk patients undergoing coronary artery bypass grafting were
      investigated, having cardiopulmonary bypass with a Duraflo II heparin-coated
      circuit (n = 10), an identical but uncoated circuit (n = 10), a Carmeda BioActive
      Surface heparin-coated circuit (n = 10), or an identical but uncoated circuit (n
      = 10). A standard systemic heparin dosage was used in all patients. Endothelin-1
      and the neutrophil glycoproteins lactoferrin and myeloperoxidase were quantified
      throughout the operation and 3 hours postoperatively. RESULTS: Enhanced plasma
      levels of endothelin-1, lactoferrin, and myeloperoxidase were observed during and
      after uncoated cardiopulmonary bypass, but this was not associated with clinical
      side effects. Compared with the respective uncoated controls, Duraflo II
      attenuated only the lactoferrin levels, whereas Carmeda BioActive Surface was
      associated with lower levels of both endothelin-1, lactoferrin, and
      myeloperoxidase. Of the two heparin coatings, Carmeda BioActive Surface proved
      more effective than Duraflo II in attenuating the levels of these substances.
      CONCLUSIONS: The plasma levels of endothelin-1, lactoferrin, and myeloperoxidase
      increase during cardiopulmonary bypass in coronary artery bypass grafting, but
      this has no clinical side effects in low-risk patients. The increase is
      attenuated using heparin-coated extracorporeal circuits, and then more
      effectively by Carmeda BioActive Surface than by Duraflo II.

PMID- 9146327
TI  - Rapid cooling contracture with cold cardioplegia.
AB  - BACKGROUND: Cold cardioplegia can induce rapid cooling contracture. The relations
      of cardioplegia-induced cooling contracture to myocardial temperature or myocyte
      calcium are unknown. METHODS: Twelve crystalloid-perfused isovolumic rat hearts
      received three 2-minute cardioplegic infusions (1 mmol/L calcium) at 4 degrees,
      20 degrees, and 37 degrees C in random order, each followed by 10 minutes of
      beating at 37 degrees C. Finally, warm induction of arrest by a 1-minute
      cardioplegic infusion at 37 degrees C was followed by a 1-minute infusion at 4
      degrees C. Indo-1 was used to measure the intracellular Ca2+ concentration in 6
      of these hearts. Additional hearts received hypoxic, glucose-free cardioplegia at
      4 degrees or 37 degrees C. RESULTS: After 1 minute of cardioplegia at 4 degrees,
      20 degrees, and 37 degrees C, left ventricular developed pressure rose rapidly to
      54% +/- 3%, 43% +/- 3%, and 18% +/- 1% of its prearrest value, whereas the
      intracellular Ca2+ concentration reached 166% +/- 23%, 94% +/- 4%, and 37% +/-
      10% of its prearrest transient. Coronary flow was 5.7 +/- 0.2, 8.7 +/- 0.3, and
      12.6 +/- 0.6 mL/min, respectively. Warm cardioplegia induction at 37 degrees C
      reduced left ventricular developed pressure and [Ca2+]i during subsequent 4
      degrees C cardioplegia by 16% (p = 0.001) and 34% (p = 0.03), respectively.
      Adenosine triphosphate and phosphocreatine contents were lower after 4 degrees C
      than after 37 degrees C hypoxic, glucose-free cardioplegia. CONCLUSIONS: Rapid
      cooling during cardioplegia increases left ventricular pressure, [Ca2+]i and
      coronary resistance, and is energy consuming. The absence of rapid cooling
      contracture may be a benefit of warm heart operations and warm induction of
      cardioplegic arrest.

PMID- 9146329
TI  - Pulmonary resection as an adjunct in the treatment of multiple drug-resistant
      tuberculosis.
AB  - BACKGROUND: Over the past decade the incidence of pulmonary disease due to drug
      resistant strains of Mycobacterium tuberculosis has increased worldwide. We
      reviewed our local experience to clarify the benefits and risks of pulmonary
      resection in the management of drug-resistant strains of Mycobacterium
      tuberculosis. METHODS: A retrospective review was performed of 62 patients
      undergoing pulmonary resection for drug-resistant strains of Mycobacterium
      tuberculosis between January 1990 and November 1995. RESULTS: Fifty-three percent
      were men and 47% women with an average age of 34 years (range, 16 to 72 years).
      There was one postoperative death, for a perioperative (30-day) mortality of
      1.6%. Sixteen complications occurred in 14 patients for an overall morbidity of
      23%. Eighteen of 24 patients (75%) who were persistently sputum positive at the
      time of operation immediately converted to a negative sputum smear and culture.
      For all patients who were sputum negative after operation 80% remain relapse-free
      by actuarial analysis. CONCLUSIONS: We believe that operation plays an important
      ancillary role in the treatment of drug-resistant strains of Mycobacterium
      tuberculosis. The operation can be performed with acceptable morbidity and
      mortality and must be combined with appropriate and well-monitored pre- and
      postoperative antituberculous drug therapy.

PMID- 9146330
TI  - Effects of diltiazem versus digoxin on dysrhythmias and cardiac function after
      pneumonectomy.
AB  - BACKGROUND: This prospective study was designed to determine whether diltiazem is
      superior to digoxin for the prophylaxis of supraventricular dysrhythmias (SVD)
      after pneumonectomy or extrapleural pneumonectomy (EPP) and to assess the
      influence of these drugs on perioperative cardiac function. METHODS: Seventy
      consecutive patients without previous SVD were randomly allocated immediately
      after pneumonectomy or EPP to receive diltiazem (n = 35) or digoxin (n = 35).
      Diltiazem-treated patients received a slow intravenous loading dose of 20 mg,
      followed by 10 mg intravenously every 4 hours for 24 to 36 hours, then 180 to 240
      mg orally daily for 1 month. Digoxin-treated patients received a 1-mg intravenous
      loading in the first 24 to 36 hours, then 0.125 to 0.25 mg orally daily for 1
      month. A concurrent prospective cohort of 40 patients without previous SVD, who
      did not participate in the study and underwent pneumonectomy or EPP without
      prophylaxis, served as a comparison group for SVD occurrence. Serial Doppler
      echocardiograms were performed to assess cardiac function and all patients were
      continuously monitored with Holter recorders for 3 days. Data were analyzed by
      intent-to-treat. RESULTS: In patients undergoing standard or intrapericardial
      pneumonectomy, diltiazem prevented the overall incidence of postoperative SVD
      when compared with digoxin, 0 of 21 patients versus 8 of 25 patients,
      respectively, p < 0.005. When EPP patients were included in the analysis,
      diltiazem decreased the incidence of all SVD from 11 of 35 patients (31%) to 5 of
      35 patients (14%) when compared with digoxin, p = 0.09. Digoxin-treated patients
      had a similar incidence of all SVD (31%) as concurrent controls (11 of 40
      patients [28%]). The two treated groups did not differ in right or left atrial
      size, left ventricular ejection fraction, or right heart pressure. When all
      patients were combined, those in whom SVD developed were significantly older (65
      +/- 12 years versus 55 +/- 11 years, p = 0.004) and had a longer median hospital
      stay (9 versus 6 days, p = 0.03), when compared with those in whom SVD did not
      develop, respectively. The subset of patients undergoing EPP had a greater
      incidence of atrial fibrillation and electrocardiographic changes suggestive of
      postoperative pericarditis than all other pneumonectomy patients. CONCLUSIONS:
      Diltiazem was both safe and more effective than digoxin in reducing the overall
      incidence of SVD after standard or intrapericardial pneumonectomy. Digoxin
      therapy had no effect on the incidence of postoperative SVD and is not
      recommended for prophylaxis of SVD. Dysrhythmias after pneumonectomy or EPP occur
      in older patients and are associated with a greater length of hospital stay.

PMID- 9146331
TI  - Inhaled nitric oxide at the time of harvest improves early lung allograft
      function.
AB  - BACKGROUND: Inhalation of nitric oxide (NO) has been shown to have beneficial
      effects on a variety of acute lung injuries, including lung allograft reperfusion
      injury. The purpose of the present study was to investigate the effects of
      inhaled NO at the time of harvest on function of canine left lung allografts
      after transplantation. METHODS: Ten dogs underwent left lung allotransplantation.
      Donor lungs were flushed with modified Euro-Collins solution and stored for 21
      hours at 1 degree C. Immediately after transplantation, the contralateral main
      pulmonary artery and bronchus were ligated to assess isolated allograft function.
      Hemodynamics and arterial blood gases (inspired oxygen fraction, 1.0) were
      assessed intermittently for 6 hours prior to sacrifice. Allograft myeloperoxidase
      activity and wet to dry weight ratio were assessed. Donor animals were divided
      into two groups. Group I animals (n = 5) received no NO. In group II (n = 5),
      donors received inhaled NO (60 ppm) at the time of harvest. RESULTS: Pulmonary
      vascular resistance decreased to 79.6% of baseline because of inhalation of 60
      ppm NO in group II donor animals. Thiobarbituric acid-reactive materials were
      reduced during the storage period in group II, a finding suggesting less oxidant
      injury during storage in donor lungs treated with NO. Throughout the 6-hour
      assessment, oxygenation in group II was superior to that in group I (p < 0.05).
      At 360 minutes of assessment, mean arterial oxygen tension in groups I and II was
      88.9 +/- 11.4 mm Hg and 169.1 +/- 33.0 mm Hg, respectively. Myeloperoxidase
      activity was significantly decreased in group II (p < 0.05), data indicating
      reduced neutrophil sequestration. Wet to dry weight ratio was significantly lower
      in group II. CONCLUSIONS: These data suggest that inhaled NO at the time of
      harvest improves early function of preserved lung allografts by attenuating
      oxidant injury during storage and subsequent neutrophil sequestration.

PMID- 9146332
TI  - Natural history of bronchopleural fistula after pneumonectomy: a review of 96
      cases.
AB  - BACKGROUND: Various therapeutic approaches to bronchopleural fistula have been
      reported. Its natural history, which may be key to the best therapeutic
      management, early detection, and possibly, prevention of fistula formation, has
      received little attention. METHODS: The cases of 96 patients with bronchopleural
      fistula after pneumonectomy seen over a 13-year period (1982 to 1995) were
      retrospectively analyzed. Cancer, TNM stage and histology, age, sex, side and
      size of the fistula at primary bronchoscopic diagnosis, time of occurrence after
      operation (days), cause of death, and survival after fistula formation (days)
      were analyzed. Management consisted of bronchoscopic closure with fibrin sealant
      or decalcified spongy calf bone or both, repeat thoracotomy with resection of the
      bronchial stump, thoracoplasty, or open window thoracostomy. RESULTS: Except for
      one instance, all total stump dehiscences occurred within 90 days after
      operation. Sixty-four patients (67%) died during the observation period; in 25,
      the cause of death was aspiration pneumonia. Only 2 patients who died of
      aspiration pneumonia had development of a fistula after 90 postoperative days.
      The aspiration rate dropped with increasing interval between operation and
      fistula occurrence (p = 0.000). Patient survival after fistula formation was
      positively correlated to this interval (p = 0.002). Successful fistula closure
      was achieved by surgical intervention in 21 patients and endoscopically in 11
      patients. The overall postoperative mortality rate irrespective of treatment
      method was 31%. CONCLUSIONS: The incidence of aspiration pneumonia declines
      sharply if bronchopleural fistula occurs more than 3 months after operation.
      Formation of fibrothorax apparently represents a natural protection against
      fistula formation and subsequent fatal aspiration pneumonia. Close follow-up
      during the first 3 postoperative months should detect bronchopleural fistula
      before aspiration occurs.

PMID- 9146333
TI  - Low-dose sodium nitroprusside reduces pulmonary reperfusion injury.
AB  - BACKGROUND: Reperfusion injury is a significant cause of early allograft
      dysfunction after lung transplantation. We hypothesized that direct pulmonary
      arterial infusion of an intravascular nitric oxide donor, sodium nitroprusside
      (SNP), would ameliorate pulmonary reperfusion injury more effectively than
      inhaled nitric oxide without causing profound systemic hypotension. METHODS:
      Using an isolated, ventilated, whole-blood-perfused rabbit lung model, we studied
      the effects of both inhaled and intravascular nitric oxide during lung
      reperfusion. Group I (control) lungs (New Zealand White rabbits, 3 to 3.5 kg)
      were harvested en bloc, flushed with Euro-Collins solution, and then stored
      inflated for 18 hours at 4 degrees C. Lungs were then reperfused with whole blood
      and ventilated with 60% oxygen for 30 minutes. Groups II, III, and IV received
      pulmonary arterial infusions of SNP at 0.2, 1.0, and 5.0 micrograms.kg-1.min-1,
      respectively, whereas group V was ventilated with 60% oxygen and nitric oxide at
      80 ppm during reperfusion. RESULTS: Pulmonary arterial infusions of SNP even at
      0.2 microgram.kg-1.min-1 (group II) showed significant improvements in pulmonary
      artery pressure (31.35 +/- 0.8 versus 40.37 +/- 3.3 mm Hg; p < 0.05) and
      pulmonary vascular resistance (38,946 +/- 1,269 versus 52,727 +/- 3,421
      dynes.s/cm-5; p < 0.05) when compared with control (group I) lungs after 30
      minutes of reperfusion. Infusions of SNP at 1.0 microgram.kg-1.min-1 (group III)
      showed additional significant improvements in dynamic airway compliance (1.98 +/-
      0.10 versus 1.46 +/- 0.02 mL/mm Hg; p < 0.05), venous-arterial oxygenation
      gradient (116.00 +/- 24.4 versus 34.43 +/- 2.5 mm Hg; p < 0.05), and wet-to-dry
      ratio (6.9 +/- 0.9 versus 9.1 +/- 2.2; p < 0.05) when compared with control
      (group I) lungs. Lungs that received inhaled nitric oxide at 80 ppm (group V)
      were significantly more compliant (1.82 +/- 0.13 versus 1.46 +/- 0.02 mL/mm Hg; p
      < 0.05) than control (group I) lungs. CONCLUSIONS: Pulmonary arterial infusion of
      low-dose SNP during lung reperfusion significantly improves pulmonary
      hemodynamics, oxygenation, compliance, and edema formation. These effects were
      achieved at doses of SNP that did not cause profound systemic hypotension. Direct
      intravascular infusion of SNP via pulmonary arterial catheters could potentially
      abate reperfusion injury immediately after allograft implantation.

PMID- 9146334
TI  - Improved results in the management of surgical candidates with lung cancer.
AB  - BACKGROUND: Perioperative mortality and morbidity after lung resection for
      carcinoma are generally reported to be 3% to 6% and 15% to 30%, respectively, and
      higher in the elderly and those with limited cardiopulmonary reserve. METHODS: To
      minimize this risk and extend the surgical option to more high-risk patients, we
      adopted a protocol in 1991 that included preoperative digitalis, subcutaneous
      heparin and venoocclusive stockings, aggressive perioperative pulmonary toilet,
      and video-directed limited resections for many patients with limited pulmonary
      reserve. In October 1996, we reviewed our results with 173 consecutive patients
      (median age, 60 years; range, 17 to 89 years) undergoing operation for suspected
      lung carcinoma. Forty-one patients were 70 years old or older, and 70 patients
      were considered high risk on the basis of advanced age (> or = 70 years), poor
      cardiac or pulmonary reserve, or serious medical comorbidity. Procedures included
      pneumonectomy (n = 31), lobectomy (n = 83), bilobectomy (n = 12), and limited
      resection (n = 45). Two patients had unresectable disease. RESULTS: Hospital
      mortality was 1.6% (3/173) and morbidity was experienced by 15% (26/173). Among
      the high-risk subgroup mortality was 4.2% (3/70) and morbidity was 20% (14/70; p
      < 0.03). For the older patients these values were 4.8% (2/41) and 17.9% (7/41),
      respectively. CONCLUSIONS: Morbidity and mortality from lung resections may be
      minimized with the perioperative management strategy outlined above. This would
      allow more high-risk patients to benefit from surgical resection, and do so with
      an acceptably low risk.

PMID- 9146335
TI  - Pain treatment after thoracotomy: is it a special problem?
AB  - BACKGROUND: Although it is frequently stated in the literature that thoracotomy
      is one of the most painful operative incisions, few data supporting this view are
      available. METHODS: Patients' postoperative pain experience can be assessed on
      the basis of their usage of patient-controlled analgesia. In a prospective trial
      the daily self-administered doses of analgesics in 55 patients within the first 4
      days after posterolateral thoractomy were compared with those in 30 patients for
      the same number of days after median laparotomy. The visual analog scale was used
      as a second measure to evaluate postoperative pain. RESULTS: On the basis of
      patient-controlled analgesia usage on the first postoperative day and the visual
      analog scale score for the first 2 days, a small but significant difference
      between the two patient groups was found which showed that thoracotomy is less
      painful than median laparotomy. CONCLUSIONS: The common belief that
      posterolateral thoracotomy is a very painful operative access is not true.
      Therefore it is not necessary to use special techniques for postthoracotomy pain
      relief in these patients. Patient-controlled analgesia is sufficient for pain
      relief after major thoracic or abdominal incisions.

PMID- 9146337
TI  - Esophagectomy for cancer in the patient aged 70 years and older.
AB  - BACKGROUND: Advanced age increases the risk of any major surgical intervention,
      particularly esophageal resection. High morbidity and increased mortality have
      been reported in operations for esophageal cancer in the elderly. METHODS: To
      determine outcome, risk factors, and the advisability of esophageal resection in
      the elderly, a single-institution retrospective review was performed of
      esophagectomy for cancer over a 14-year period. From January 1, 1980, to December
      31, 1993, 540 patients underwent esophageal resection for esophageal cancer.
      These patients were divided into two groups: group 1, n = 89, patients 70 years
      of age or older; and group 2, n = 451, patients younger than 70 years of age. The
      two groups were compared according to preoperative risk factors, morbidity rate,
      mortality rate, mean stay in the hospital after operation, and long-term
      survival. RESULTS: Adenocarcinoma of the esophagogastric junction was the most
      common tumor in group 1 and was usually managed with a single incisional
      approach. There were no significant differences between the groups concerning
      morbidity (24.7% in group 1), mortality (7.8% in group 1), mean stay in the
      hospital (23.3 days in group 1), or long-term survival (59%, 23%, and 13% at 1,
      3, and 5 years, respectively, in group 1). CONCLUSIONS: These results suggest
      that esophagectomy can be performed in selected elderly patients without
      increasing morbidity or mortality and with long-term survival.

PMID- 9146336
TI  - One hundred video-assisted thoracic surgical simultaneously stapled lobectomies
      without rib spreading.
AB  - BACKGROUND: This study was performed to evaluate and determine the validity and
      benefits of video-assisted thoracic surgical simultaneously stapled pulmonary
      lobectomy without rib spreading. METHODS: Between September 1992 and August 1995,
      100 consecutive video-assisted thoracic surgical simultaneously stapled
      lobectomies without rib spreading were performed. RESULTS: Forty-five male and 55
      female patients had 24 right upper, 8 right middle, 29 right lower, 24 left
      upper, 15 left lower lobectomies for 66 adenocarcinomas, 20 squamous cell
      carcinomas, 4 large cell carcinomas, 8 benign lesions, and 2 metastatic lesions.
      Seventy-six patients had negative nodes. Nine patients had positive nodes. Every
      bronchoscopy was visually and cytologically negative. Forty-nine cervical
      mediastinoscopies were negative. Operating time for the series averaged 90.3
      minutes. Hospitalization averaged 3.5 days for the entire group, but was 2.6 days
      for the last 20 patients. Lesions ranged from 1.5 to 8 cm, averaging 3.4 cm.
      There was no surgical mortality, no hemorrhage, no transfusion, and no urgent
      conversion to an open procedure. No bronchial fistula, vascular fistula, or
      bronchovascular fistula has occurred. Complications included 6 air leaks, 2
      cerebrovascular accidents, 1 infected chest tube site, 2 cases of pneumonitis,
      and 1 subcutaneous emphysema. CONCLUSIONS: Video-assisted thoracic surgical
      simultaneously stapled lobectomy without rib spreading is a safe operation that
      can be combined with lymph node sampling. At this early stage, therapeutic
      outcomes (survival) for resected neoplasms appear similar to results obtained
      from traditional open techniques.

PMID- 9146338
TI  - Effects of lung preservation with Euro-Collins and University of Wisconsin
      solutions on endothelium-dependent relaxations.
AB  - BACKGROUND: This study compares the effect of lung preservation using flush
      perfusion of Euro-Collins or University of Wisconsin solution on the pulmonary
      vascular function of endothelium-dependent and endothelium-independent
      relaxations. METHODS: Rings of canine intrapulmonary arteries were studied after
      6 hours of cold ischemia in Euro-Collins or University of Wisconsin preservation
      solution. Endothelium-dependent and endothelium-independent relaxations were
      induced in organ chamber experiments. To also study pulmonary resistance vessels,
      endothelium-dependent relaxations were induced in in vitro perfused intact rabbit
      lungs. RESULTS: In the organ chamber experiments, a moderate but significant (p <
      0.05) reduction in endothelium-dependent relaxations were found in the perfused
      and stored vessels. In perfused rabbit lungs, a decrease in the endothelial
      response occurred immediately after perfusion with Euro-Collins solution.
      However, a recovery and overshooting response was found after preservation with
      either solution and 6 hours of cold ischemia. A significant increase in the
      sensitivity of smooth muscle cells to nitric oxide was shown in both
      preparations. CONCLUSIONS: Both crystalloid perfusion fluids cause a decrease in
      endothelial function during the perfusion procedure. In contrast, endothelial
      function is well preserved during the ischemic time. University of Wisconsin
      solution induced a higher sensitivity of the vascular smooth muscle to the
      endothelium-derived relaxing factor nitric oxide. A reduction in pulmonary
      vascular resistance after University of Wisconsin preservation may be of
      importance in subsequent clinical lung transplantation.

PMID- 9146339
TI  - Lymph node type as a prognostic factor for survival in T2 N1 M0 non-small cell
      lung carcinoma.
AB  - BACKGROUND: Patients with stage II non-small cell lung carcinoma represent a
      group with varying 5-year survival rates. The influence of specific types of
      lymph node involvement on survival was investigated. METHODS: Of 2,009 patients
      operated on from 1977 through 1993, the cases of 391 patients with pathologic T2
      N1 M0 disease were reviewed. The N1 status was refined into lymph node
      involvement by direct extension or by metastases in lobar or hilar lymph nodes.
      RESULTS: The cumulative 5-year survival rate of all hospital survivors (n = 369)
      was 37.8%. The 5-year survival rate of patients with lobar metastases was
      superior to that of patients with hilar metastases (57.3% versus 30.3%; p =
      0.0028) and that of patients with lymph node involvement by direct extension
      (57.3% versus 39.1%; p = 0.03). The survival rate did not differ between those
      with hilar metastases and those with direct extension. Survival was significantly
      poorer in patients with visceral pleural involvement, in patients with
      adenocarcinoma, and in patients older than 60 years. Survival was not related to
      sex, type of resection, central growth, or tumor size. CONCLUSIONS: Survival
      differs according to the type of lymph node involvement: lobar lymph node
      metastasis seems to be an early stage of the disease, whereas hilar lymph node
      metastasis represents a more advanced form. However, in T2 N1 M0 disease, other
      factors besides nodal status also seem to play an important role in postoperative
      survival.

PMID- 9146340
TI  - Survival and prognostic factors in resected N2 non-small cell lung cancer: a
      study of 140 cases. Leuven Lung Cancer Group.
AB  - BACKGROUND: The selection of stage IIIA N2 non-small cell lung cancer patients
      for primary surgical treatment remains controversial. METHODS: One hundred forty
      patients with resected non-small cell lung cancer who eventually proved to have
      pathologic N2 disease were studied with a univariate and multivariate analysis of
      prognostic factors. RESULTS: Nineteen patients had a positive mediastinoscopy;
      the others had a preoperative N0 or N1 stage. Complete resection rate was 80.7%.
      Five-year survival was 20.8% (95% confidence interval, 17.2% to 24.4%), 32.2% in
      mediastinoscopy-negative patients. In the univariate analysis, clinical N stage
      at mediastinoscopy, complete resection, performance status, T stage, number of
      metastatic levels in adenocarcinoma, and nodal capsule rupture were important
      factors. In a multivariate model, survival was worse in case of higher T stage
      (relative risk = 1.43), lower performance status (relative risk = 1.37),
      involvement of more than one node level (relative risk = 1.68), nonsquamous
      histology (relative risk = 1.29) and clinical N2 stage (relative risk = 1.43).
      Long-term survival was unlikely when lactic dehydrogenase or carcinoembryonic
      antigen levels were elevated. CONCLUSIONS: In clinical N0 or N1 cancer, complete
      resection resulted in reasonable survival prospects. In patients with N2 disease
      discovered at mediastinoscopy, surgical treatment was only worthwhile in case of
      minimal N2. Several unfavorable prognostic factors could be identified in the
      univariate analysis and confirmed in a multivariate Cox model.

PMID- 9146341
TI  - Dyspnea after pneumonectomy: the result of an atrial septal defect.
AB  - We report the case of severe hypoxemia attributable to right-to-left shunting
      through an atrial septal defect after right-sided pneumonectomy that developed in
      a 70-year-old man. Normal right atrial and pulmonary artery pressures were
      measured. Right-to-left shunting through a patent foramen ovale is known as a
      rare complication after pneumonectomy. Our patient, however, demonstrated a true
      atrial septal defect (septum secundum defect) upon open operative repair of the
      interatrial connection.

PMID- 9146342
TI  - Multiple-leaflet mitral valve as a rare cause of congenital mitral insufficiency.
AB  - A rare case of congenital mitral insufficiency characterized by six well
      demarcated leaflets of mitral valve and annular dilatation is reported. At
      operation, the mitral valve was successfully repaired by resection of the
      posterior median leaflet with subsequent annular plication, closure of unusual
      valvular tissue divisions, and ring annuloplasty.

PMID- 9146343
TI  - Traumatic lung herniation.
AB  - Traumatic lung herniation is a poorly described entity. An important factor in
      the etiology of these lesions is the relative lack of muscular support afforded
      by the anterior thorax. We report a case of blunt thoracic trauma complicated by
      an incarcerated lung herniation.

PMID- 9146344
TI  - Surgical repair of a large residual atrial septal defect after transcatheter
      closure.
AB  - Transcatheter closure of ostium secundum atrial septal defects is a less invasive
      method of repairing atrial septal defects in comparison with an open heart
      operation. In selected patients the transvenous closure of atrial septal defects
      may be an effective alternative. Defects with circumferential septal rims,
      secundum atrial defects, and patent foramen are the best candidates for this
      method. We report a case in which a large residual atrial septal defect after
      transvenous closure with a Sideris occluder device required surgical closure.

PMID- 9146345
TI  - Permanent mechanical circulatory support with an implantable left ventricular
      assist device.
AB  - A 67-year-old man had end-stage ischemic cardiomyopathy. He had had two previous
      coronary bypass operations and a previous left ventricular aneurysmectomy. In
      December 1995 he underwent vented-electric HeartMate LVAD insertion as an
      alternative to transplantation. He was discharged from the hospital 13 days after
      the operation, and 5 months postoperatively he had returned to New York Heart
      Association functional class II.

PMID- 9146346
TI  - Surgical therapy of primary malignant melanoma of the esophagus.
AB  - Primary malignant melanoma of the esophagus is an extremely rare tumor. In the
      absence of prospectively sampled data in the literature, the following case
      report and review of the literature indicate that surgical resection of the
      primary tumor and solitary metastases provides the longest survival times and, to
      date, is the treatment of choice.

PMID- 9146347
TI  - Mitral valve replacement and tricuspid valve repair after cardiac
      transplantation.
AB  - Efforts aimed at limiting the pool of cardiac retransplantation candidates have
      focused increasingly on attempts to preserve cardiac allograft function. The
      present report reviews the course of a patient who underwent mitral valve
      replacement and tricuspid annuloplasty for bivalvular incompetence after cardiac
      transplantation and examines the limited reported world experience with valve
      replacement after transplantation. The limited yet successful experiences with
      these and other operations in cardiac allograft recipients suggest that worsening
      donor organ shortages will likely lead to increased clinical experience with
      conventional operations in the transplanted heart.

PMID- 9146348
TI  - Cardiac pacemaker dysfunction in children after thoracic drainage catheter
      manipulation.
AB  - Two children underwent placement of permanent, epicardial-lead, dual-chamber,
      unipolar pacemaker systems for complete heart block. Postoperatively, both
      patients demonstrated subcutaneous emphysema-in the area of their pulse
      generators-temporally related to thoracic catheter manipulation. Acutely, each
      situation was managed with manual compression of the pulse generator,
      ascertaining appropriate pacemaker sensing and pacing. Maintenance of compression
      with pressure dressings, vigilant observation/monitoring, and education of the
      care givers resulted in satisfactory pacemaker function without invasive
      intervention.

PMID- 9146349
TI  - Simultaneous single-lung transplantation and lung volume reduction.
AB  - We report our experience with 2 cases of simultaneous single-lung transplantation
      and lung volume reduction for emphysema. The lung volume reduction was undertaken
      electively in an attempt to improve overall lung function above that to be
      expected from single-lung transplantation alone. There were no postoperative
      problems related to the addition of lung volume reduction. The pulmonary function
      at 3 months was greater than that seen in a retrospective group of bilateral lung
      transplants previously reported from our institution.

PMID- 9146351
TI  - Recurrent left ventricular false aneurysm.
AB  - A recurrent left ventricular false aneurysm 5 years after patch repair and
      causing progressive congestive heart failure was readily diagnosed by
      echocardiography and heart catheterization. Its substrate was suture dehiscence
      of undetermined origin. Urgent repair was successful. The long-term prognosis is
      guarded.

PMID- 9146350
TI  - Ischemic gastric ulcer after coronary bypass using the right gastroepiploic
      artery.
AB  - The gastroepiploic artery has been widely used for complete arterial myocardial
      revascularization of young patients. Gastric complications related to the
      harvesting of this artery are exceptional. We describe here a case of ischemic
      gastric ulcer due to the use of a gastroepiploic artery in a patient with severe
      celiac trunk disease. The patient was cured by angioplasty completed by a
      stenting procedure.

PMID- 9146352
TI  - Diagnosis and repair of a Morgagni hernia with video-assisted thoracic surgery.
AB  - Foramen of Morgagni hernias have traditionally been repaired by either an
      abdominal or a transthoracic approach. We describe a case in which a Morgagni
      hernia that presented as a gradually enlarging right anterior pericardiophrenic
      mass was both diagnosed and repaired using video-assisted thoracic surgery. The
      procedure went without incident, and the patient had an uneventful postoperative
      course. The video-assisted thoracic surgical repair can be a safe and effective
      way to fix a Morgagni hernia.

PMID- 9146353
TI  - MRI in the evaluation and management of a newborn infant with cardiac
      rhabdomyoma.
AB  - A newborn infant presented with a life-threatening cardiac arrhythmia.
      Echocardiography showed a large cardiac mass growing exophytically in the region
      of the left atrial appendage extending along the left ventricular wall but showed
      no clear tissue plane between the mass and the left ventricular wall. Based on
      the echocardiogram, surgical resection might damage the left ventricular wall.
      Magnetic resonance imaging demonstrated a clear plane of demarcation, making
      surgical resection a viable life-saving option.

PMID- 9146354
TI  - Minimally invasive mitral valve repair using transthoracic aortic occlusion.
AB  - This report describes a minimally invasive mitral valve repair done through a
      limited (6-cm) thoracic incision. The patient was supported by peripheral
      extracorporeal perfusion with cardiac arrest established using a new
      transthoracic aortic cross-clamp and antegrade blood cardioplegia. The patient
      was discharged on postoperative day 3 with minimal pain. This less invasive
      approach to mitral valve surgery may offer combined advantages to patients by
      increasing comfort, expediting recovery, and decreasing surgical costs by using
      modified traditional methods compared with specialized intraaortic occlusive
      balloons.

PMID- 9146355
TI  - Successful surgical treatment of a complete traumatic tracheal disruption.
AB  - We report a case of a survivor who suffered a complete traumatic disruption of
      the cervical trachea associated with multiple organ injuries. She underwent an
      emergent operation including end-to-end anastomosis of the disrupted trachea with
      pedicled omental coverage to prevent dehiscence and mediastinitis. The
      postoperative course was uneventful, with hospital discharge on day 36. She
      returned to her previous lifestyle.

PMID- 9146356
TI  - Mitral homograft replacement of the tricuspid valve for endocarditis.
AB  - An infected tricuspid valve was successfully replaced with a fresh mitral
      homograft. This operation is preferable to valvectomy alone or the use of a
      stented prosthesis in terms of hemodynamics and resistance to infection.

PMID- 9146357
TI  - Repair of congenital pulmonary incompetence by bicuspidization of the pulmonary
      valve.
AB  - We report the successful repair of pulmonary incompetence in an adult due to the
      congenital absence of the posterior leaflet of the pulmonary valve. The repair
      consisted of bicuspidization of the pulmonary valve, which achieved competence
      and eliminated the symptoms and echocardiographic manifestations of right
      ventricular overload while preserving the native valve.

PMID- 9146358
TI  - Retrosternal fat pad for prevention of suppurative sternitis.
AB  - An increased incidence of postoperative sternal infection has been reported after
      the use of bilateral internal mammary arteries for coronary artery grafting. In
      this series, a pedicled pericardial fat pad was mobilized to lie in the
      retrosternal space before the sternum was approximated. This technique was used
      in 101 consecutive patients who underwent coronary artery grafting using
      bilateral internal mammary arteries. Twenty-four percent of the patients were
      diabetic. No suppurative sternitis developed in any of these patients.

PMID- 9146359
TI  - Preperitoneal suprahepatic pacemaker generator placement in the pediatric
      population.
AB  - We have used a preperitoneal suprahepatic location for pacemaker generator
      placement in pediatric patients requiring permanent pacemakers with epicardial
      leads. The technique is rapid, simple, and safe, and cosmesis is excellent,
      making this approach particularly advantageous in the younger infant and neonate.

PMID- 9146360
TI  - Technique to repair tetralogy of Fallot with absent pulmonary valve.
AB  - The syndrome of tetralogy of Fallot with absent pulmonary valve is characterized
      by aneurysmal dilatation of the pulmonary arteries causing tracheobronchial
      obstruction of varying degree. Relief of this obstruction is the main goal of the
      surgical repair and can best be achieved by appropriate pulmonary arterioplasty.
      We describe our current technique to repair this syndrome in infants and older
      children including pulmonary arterioplasty, ventricular septal defect closure,
      and right ventricular outflow tract reconstruction without valve insertion.

PMID- 9146361
TI  - Management of the uncontrollable pulmonary air leak with cyanoacrylate glue.
AB  - Massive pulmonary air leak from a ruptured bleb in a patient with emphysema may
      be uncontrollable by the usual methods. A technique is illustrated where fibrin
      glue, cyanoacrylate glue, and a bovine pericardial patch are used in combination
      to seal the leak.

PMID- 9146362
TI  - A dedicated prosthesis for open thoracostomy.
AB  - Due to our dissatisfaction with the mutilation caused by the skin-lined open
      thoracostomy, we have developed a dedicated prosthesis that is expected to avoid
      or to substitute for the classic operation. The prosthesis is a corrugated
      silicone tube with an oval flange at one end (to fix it internally) and a mobile
      ring on the other (to fix it externally). It is inserted at the bottom of the
      empyematic cavity after 3 cm of a rib is removed. We have used it in 20 patients
      whose empyema was secondary to pneumonia (12) or complications of pneumonectomy
      (4), lobectomy (2), decortication (1), or pleuroscopy (1). Six of those patients
      have already been cured and their prosthesis removed after 54 to 305 days. In 1
      with a persistent postpneumonectomy bronchopleural fistula the device was removed
      after 299 days and the patient was submitted to a limited thoracoplasty. Six
      other patients still have unresolved cavities and have been using the prosthesis
      for 63 to 302 days. Seven patients died of their underlying disease (bilateral
      pneumonia, 2; acquired immunodeficiency syndrome, 2; mesothelioma, 1; heart
      failure and pulmonary embolism, 1; unknown, 1) after using the prosthesis for 11
      to 160 days. In those patients from whom the prosthesis already has been removed,
      the scar looks like those commonly seen after removal of an ordinary chest tube.
      Based on these early favorable results we feel most encouraged to persist in this
      research. Nevertheless, we are aware that a larger number of patients and a
      longer follow-up will be necessary before we may make definitive recommendations.

PMID- 9146363
TI  - Thoracic drainage.
AB  - The evacuation of empyemas first performed centuries ago, marked the beginning of
      thoracic drainage. The subsequent acquisition of a greater knowledge of the
      anatomy, physiology, and pathology of the pleural space directed the design of
      thoracic catheters and drainage systems and the development of the methods by
      which they are used. Furthermore, a better understanding of the physics of vacuum
      and air flow brought about improvements in the use of suction with drainage.
      Today, thoracic catheters, chest drainage systems, and most vacuum sources are
      well designed and well made and incorporate components needed to achieve the best
      care of the pleural-mediastinal space. This review covers the development and
      important considerations in the current use of thoracic drainage.

PMID- 9146364
TI  - Malignant mesothelioma.

PMID- 9146365
TI  - As originally published in 1989: Thermal coronary angiography: a method for
      assessing graft patency and coronary anatomy in coronary bypass surgery. Updated
      in 1997.

PMID- 9146366
TI  - As originally published in 1989: Correlates of survival in patients with
      postinfarction ventricular septal defect. Updated in 1997.

PMID- 9146367
TI  - Traumatic subarachnoid-pleural fistula.

PMID- 9146368
TI  - Troponin-T in minimally invasive coronary operations.

PMID- 9146369
TI  - Which stent to use for tracheobronchial stenoses: metallic or silicone?

PMID- 9146370
TI  - Role of intraoperative autotransfusion after cardiopulmonary bypass.

PMID- 9146371
TI  - Calcification in cardiac bioprostheses.

PMID- 9146372
TI  - Double stents for carcinoma of the esophagus invading the airway.

PMID- 9146373
TI  - Endovascular aneurysm repair.

PMID- 9146374
TI  - Allocating donor livers.

PMID- 9146375
TI  - Safe tissue grafts.

PMID- 9146376
TI  - Alcohol policy in the Nordic countries.

PMID- 9146377
TI  - Women's autonomy in childbirth.

PMID- 9146378
TI  - Research suppressed for seven years by drug company.

PMID- 9146379
TI  - Doctors fight US company patent on umbilical cord blood.

PMID- 9146380
TI  - Sweden is healthiest place to live in world.

PMID- 9146381
TI  - E coli report calls for better food safety.

PMID- 9146382
TI  - UN condemns female circumcision.

PMID- 9146386
TI  - Boycott threat forces French company to abandon RU486.

PMID- 9146387
TI  - Collaborative systematic review of the randomised trials of organised inpatient
      (stroke unit) care after stroke. Stroke Unit Trialists' Collaboration.
AB  - OBJECTIVES: To define the characteristics and determine the effectiveness of
      organised inpatient (stroke unit) care compared with conventional care in
      reducing death, dependency, and the requirement for long term institutional care
      after stroke. DESIGN: Systematic review of all randomised trials which compared
      organised inpatient stroke care with the contemporary conventional care.
      Specialist stroke unit interventions were defined as either a ward or team
      exclusively managing stroke (dedicated stroke unit) or a ward or team
      specialising in the management of disabling illnesses, which include stroke
      (mixed assessment/rehabilitation unit). Conventional care was usually provided in
      a general medical ward. SETTING: 19 trials (of which three had two treatment
      arms). 12 trials randomised a total of 2060 patients to a dedicated stroke unit
      or a general medical ward, six trials (647 patients) compared a mixed
      assessment/rehabilitation unit with a general medical ward, and four trials (542
      patients) compared a dedicated stroke unit with a mixed assessment/rehabilitation
      unit. MAIN OUTCOME MEASURES: Death, institutionalisation, and dependency.
      RESULTS: Organised inpatient (stroke unit) care, when compared with conventional
      care, was best characterised by coordinated multidisciplinary rehabilitation,
      programmes of education and training in stroke, and specialisation of medical and
      nursing staff. The stroke unit care was usually housed in a geographically
      discrete ward. Stroke unit care was associated with a long term (median one year
      follow up) reduction of death (odds ratio 0.83, 95% confidence interval 0.69 to
      0.98; P < 0.05) and of the combined poor outcomes of death or dependency (0.69,
      0.59 to 0.82; P < 0.0001) and death or institutionalisation (0.75, 0.65 to 0.87;
      P < 0.0001). Beneficial effects were independent of patients' age, sex, or stroke
      severity and of variations in stroke unit organisation. Length of stay in a
      hospital or institution was reduced by 8% (95% confidence interval 3% to 13%)
      compared with conventional care but there was considerable heterogeneity of
      results. CONCLUSIONS: Organised stroke unit care resulted in long term reductions
      in death, dependency, and the need for institutional care. The observed benefits
      were not restricted to any particular subgroup of patients or model of stroke
      unit care. No systematic increase in the use of resources (in terms of length of
      stay) was apparent.

PMID- 9146388
TI  - How much alcohol and how often? Population based case-control study of alcohol
      consumption and risk of a major coronary event.
AB  - OBJECTIVE: To quantify the effects of quantity and frequency of alcohol
      consumption on risk of acute myocardial infarction and coronary death. DESIGN:
      Case-control study. SETTING: Lower Hunter region of New South Wales, Australia,
      1983-94. SUBJECTS: Men and women aged 35-69 years. MAIN OUTCOME MEASURE: Acute
      myocardial infarction or coronary death. RESULTS: Alcohol consumption patterns
      were compared between 11,511 cases of acute myocardial infarction or coronary
      death and 6077 controls randomly selected from the same study population. After
      adjusting for the effects of age, smoking, and medical history, men and women who
      consumed one or two drinks of alcohol on five or six days a week had a reduction
      in risk of a major coronary event compared with men and women who were non
      drinkers (odds ratios: men 0.31 (95% confidence interval 0.22 to 0.45); women
      0.33 (0.18 to 0.59)). A similar reduction in risk was found after excluding non
      drinkers who were formerly moderate to heavy drinkers. An acute protective effect
      of alcohol consumption was also found for regular drinkers who consumed one or
      two drinks in the 24 hours preceding the onset of symptoms (odds ratios: men 0.74
      (0.51 to 1.09); women 0.43 (0.20 to 0.95)). CONCLUSIONS: Frequency and quantity
      of alcohol consumption are important in assessing the risk of a major coronary
      event. Risk is lowest among men who report one to four drinks daily on five or
      six days a week and among women who report one or two drinks daily on five or six
      days a week.

PMID- 9146389
TI  - Ecological analysis of collectivity of alcohol consumption in England: importance
      of average drinker.
AB  - OBJECTIVE: To assess whether the average consumption of alcohol is associated
      with the prevalence of heavy drinking, problem drinking, and abstention in
      England. DESIGN: Ecological analysis using data from a cross sectional household
      based survey of English adults. SUBJECTS: Random sample of 32,333 adults from the
      English population who participated in the 1993 and 1994 health surveys for
      England. MAIN OUTCOME MEASURES: Association, expressed as the correlation
      coefficient, between the regional mean and median alcohol consumption and the
      regional prevalence of heavy drinking, problem drinking, and abstention. RESULTS:
      Mean consumption of alcohol in light to moderate drinkers was strongly positively
      associated with the prevalence of heavy drinking (r = 0.75 in men and r = 0.62 in
      women for drinking more than 21 and 14 units per week respectively). A similar
      association was found between median consumption and prevalence of heavy
      drinking. Abstention was not significantly associated with mean consumption in
      drinkers (r = 0.08 for men and r = -0.29 for women). Both the median and mean
      consumption in drinkers were positively associated with the prevalence of problem
      drinking as defined by the CAGE questionnaire on alcohol use (r = 0.53 for men
      and r = 0.42 for women for the association with mean consumption). CONCLUSION:
      Factors that increase the average consumption of alcohol in the population may
      result in an increase in the prevalence of heavy drinking and related problems.

PMID- 9146390
TI  - Assessment of the zinc turbidity test and the use of risk factors in detecting
      asymptomatic hepatitis C virus carriers: population based study.

PMID- 9146391
TI  - Do general practitioners act consistently in real practice when they meet the
      same patient twice? Examination of intradoctor variation using standardised
      (simulated) patients.
AB  - OBJECTIVE: To assess the variation within individual general practitioners facing
      the same problem twice in actual practice under unbiased conditions. DESIGN:
      General practitioners were consulted during normal surgery hours by a
      standardised patient portraying a patient with angina pectoris. Six weeks later
      the same general practitioners were consulted again by a similar standardised
      patient portraying a similar case. The patients reported on the consultations.
      SETTING: Trondheim, Norway. SUBJECTS: Of 87 general practitioners invited by
      letter, 28 (32%) agreed to participate without hesitation; nine others (10%)
      wanted more information before consenting. From these 24 were selected and
      visited. MAIN OUTCOME MEASURES: Number of actions undertaken from a guideline in
      both rounds of consultations. Duration of consultations. RESULTS: The mean
      (range, interquartile range) guideline score, total score, and duration of
      consultation were not significantly different between the first and second
      patient encounters for the group as a whole. For individual doctors the mean (SD)
      difference was -0.09 (3.36) for the guideline score, 0.30 (8.1) for the total
      score, and -0.87 (9.01) for consultation time. CONCLUSIONS: The study shows that
      assessment of performance in real practice for a group of general practitioners
      is consistent from the first round of consultations to the second round. However,
      significant variation occurs in performance of individual physicians.

PMID- 9146392
TI  - Survey of general practitioners' opinions on treatment of opiate users.

PMID- 9146393
TI  - Hypothyroidism: screening and subclinical disease.

PMID- 9146394
TI  - ABC of clinical haematology. Bone marrow and stem cell transplantation.

PMID- 9146395
TI  - Caesarean section: a treatment for mental disorder? Tameside & Glossop Acute
      Services Unit v CH (a patient) [1996] 1 FLR 762.

PMID- 9146399
TI  - Equity, poverty and health for all.

PMID- 9146400
TI  - Are placebo run ins justified?

PMID- 9146402
TI  - Health and the life course: why safety nets matter.
AB  - This article argues that a life course approach is necessary to understand social
      variations in health. This is needed in order to take into account the complex
      ways in which biological risk interacts with economic, social, and psychological
      factors in the development of chronic disease. Such an approach reveals
      biological and social "critical periods" during which social policies that will
      defend individuals against an accumulation of risk are particularly important. In
      many ways, the authors of modern welfare states were implicitly addressing these
      issues, and the contribution of these policies to present day high standards of
      health in developed countries should not be ignored.

PMID- 9146403
TI  - Out of hours primary care. Attitudes are evidence of change.

PMID- 9146404
TI  - Out of hours primary care. What patients like may not be what they need.

PMID- 9146405
TI  - Out of hours primary care. Appropriateness of demand should be included in
      assessments of quality of care.

PMID- 9146406
TI  - Out of hours primary care. Study should have considered other published work,
      deprivation, seasonal variation, and need.

PMID- 9146407
TI  - Out of hours primary care. Patients in inner city east London like primary care
      centres.

PMID- 9146408
TI  - Out of hours primary care. We gave our patients three different out of hours
      services and recorded their activity.

PMID- 9146411
TI  - Managing a fish induced injury.

PMID- 9146412
TI  - Childhood leukaemia in US may have risen due to fallout from Chernobyl.

PMID- 9146413
TI  - How to minimise factitious hyperkalaemia in blood samples from general practice.

PMID- 9146414
TI  - Do fetuses feel pain? Surgical terminations of pregnancy take place under general
      anaesthesia.

PMID- 9146415
TI  - Do fetuses feel pain? Definition of pain needs clarification.

PMID- 9146417
TI  - Some patients may want to retain ownership of tissue removed from them.

PMID- 9146416
TI  - Do fetuses feel pain? Analgesic and anaesthetic procedures are being introduced
      because of shoddy sentimental argument.

PMID- 9146418
TI  - Social deprivation increases workload in palliative care of terminally ill
      patients.

PMID- 9146419
TI  - Bayesian statistics may inform public policy better than significant odds ratios.

PMID- 9146420
TI  - Benefits Agency always holds consent before approaching healthcare professionals
      for information.

PMID- 9146421
TI  - Interpersonal skills are being taught better, but more work is needed.

PMID- 9146422
TI  - MeSH terms must be used in Medline searches.

PMID- 9146423
TI  - Caution is required when using new analgesics by the spinal route in children.

PMID- 9146424
TI  - The Eating Patterns Study--the importance of practical randomized trials in
      communities.

PMID- 9146425
TI  - Annotation: cigarette smoking, nutrition, and birthweight.

PMID- 9146426
TI  - Annotation: HIV prevention challenges-realistic strategies and early detection
      programs.

PMID- 9146427
TI  - Annotation: wanted--a simple and meaningful HIV staging system.

PMID- 9146428
TI  - Annotation: what can be done about missing data? Approaches to imputation.

PMID- 9146429
TI  - Topics for our times: Norplant coercion--an overstated threat.

PMID- 9146430
TI  - Topics for our times: the increasing demand for tuberculosis services--a new
      encumbrance on tuberculosis control programs.

PMID- 9146431
TI  - Leadership to meet the challenges to the public's health.

PMID- 9146432
TI  - Increased condom use without other major changes in sexual behavior among the
      general population in Switzerland.
AB  - OBJECTIVES: This study is part of a continuous evaluation of the Swiss AIDS
      prevention strategy from 1987 through 1994. METHODS: Annual telephone surveys of
      samples representative of the general population aged 17 through 45 years have
      been conducted since 1987 to monitor behavioral change. RESULTS: No major changes
      in level of sexual activity (lifetime number of partners, frequency of sexual
      encounters in the past week) or potential exposure to risk of HIV transmission
      (acquisition of a new steady partner during the year or of casual partners in the
      last 6 months) were observed. Systematic condom use with a new steady partner
      increased between 1988 and 1994, from 40% to 64% among 17- to 30-year-olds and
      from 57% to 72% among those aged 31 to 45. Systematic condom use with casual
      partners increased from 8% to 56% between 1987 and 1994 among 17- to 30-year-olds
      and from 22% to 42% between 1989 and 1994 among those aged 31 to 45. Condom use
      was higher among those with multiple partners. CONCLUSIONS: A general-population
      approach to AIDS prevention was able to achieve large-scale improvements in
      condom-based protection against HIV infection without inducing other major
      changes in sexual behavior.

PMID- 9146434
TI  - The role of diabetes mellitus in the higher prevalence of tuberculosis among
      Hispanics.
AB  - OBJECTIVES: This research studied the relative contribution of diabetes mellitus
      to the increased prevalence of tuberculosis in Hispanics. METHODS: A case-control
      study was conducted involving all 5290 discharges from civilian hospitals in
      California during 1991 who had a diagnosis of tuberculosis, and 37,366 control
      subjects who had a primary discharge diagnosis of deep venous thrombosis,
      pulmonary embolism, or acute appendicitis. Risk of tuberculosis was estimated as
      the odds ratio (OR) across race/ethnicity, with adjustment for other factors.
      RESULTS: Diabetes mellitus was found to be an independent risk factor for
      tuberculosis. The association of diabetes and tuberculosis was higher among
      Hispanics (adjusted OR [ORadj] = 2.95: 95% confidence interval [CI] = 2.61, 3.33)
      than among non-Hispanic Whites (ORadj = 1.31: 95% CI = 1.19. 1.45): among non
      Hispanic Blacks, diabetes was not found to be associated with tuberculosis (ORadj
      = 0.93: 95% CI = 0.78, 1.09). Among Hispanics aged 25 to 54, the estimated risk
      of tuberculosis attributable to diabetes (25.2%) was equivalent to that
      attributable to HIV infection (25.5%). CONCLUSIONS: Diabetes mellitus remains a
      significant risk factor for tuberculosis in the United States. The association is
      especially notable in middle-aged Hispanics.

PMID- 9146433
TI  - The Boston AIDS Survival Score (BASS): a multidimensional AIDS severity
      instrument.
AB  - OBJECTIVES: This study developed a new acquired immunodeficiency syndrome (AIDS)
      severity system by including diagnostic, physiological, functional, and
      sociodemographic factors predictive of survival. METHODS: Three-hundred five
      persons with AIDS in Boston were interviewed; their medical records were reviewed
      and vital status ascertained. RESULTS: Overall median (+/- SD) survival for the
      cohort from the first interview until death was 560 +/- 14.4 days. The best model
      for predicting survival, the Boston AIDS Survival Score, included the Justice
      score (stage 2 relative hazard [RH] = 1.25, 95% confidence interval [CI] = 0.80,
      1.96; stage 3 RH = 1.76, 95% CI = 1.15, 2.70), a newly developed opportunistic
      disease score (Boston Opportunistic Disease Survival Score; stage 2 RH = 1.35,
      95% CI = 0.90, 2.02; stage 3 RH = 2.10, 95% CI = 1.38, 3.18), and measures of
      activities of daily living (any intermediate limitations, RH = 1.84, 95% CI =
      1.05, 3.21; any basic limitations, RH = 2.60, 95% CI = 1.44, 4.69). This model
      had substantially greater predictive power (R2 = .17, C statistic = .68) than the
      Justice score alone (R2 = .09, C statistic = .61). CONCLUSIONS: Incorporating
      data on clinically important events and functional status into a physiologically
      based system can improve the prediction of survival with AIDS.

PMID- 9146435
TI  - A community waterborne outbreak of salmonellosis and the effectiveness of a boil
      water order.
AB  - OBJECTIVES: A 1993 large water-borne outbreak of Salmonella typhimurium
      infections in Gideon, Mo, a city of 1100 with an unchlorinated community water
      supply, was investigated to determine the source of contamination and the
      effectiveness of an order to boil water. METHODS: A survey of household members
      in Gideon and the surrounding township produced information on diarrheal illness,
      water consumption, and compliance with the boil water order. RESULTS: More than
      650 persons were ill; 15 were hospitalized, and 7 died. Persons consuming city
      water were more likely to be ill (relative risk [RR] = 9.1, 95% confidence
      interval [CI] = 2.9, 28.4), and the attack rate increased with increased water
      consumption. S. typhimurium was recovered from samples taken from a city fire
      hydrant and a water storage tower. Persons in 31% (30/ 98) of city households had
      drunk unboiled water after being informed about the boil water order, including
      14 individuals who subsequently became ill. Reasons for noncompliance included
      "not remembering" (44%) and "disbelieving" (25%) the order. CONCLUSIONS:
      Communities with deteriorating water systems risk widespread illness unless water
      supplies are properly operated and maintained. Effective education to improve
      compliance during boil water orders is needed.

PMID- 9146436
TI  - Marijuana use and mortality.
AB  - OBJECTIVES: The purpose of this study was to examine the relationship of
      marijuana use to mortality. METHODS: The study population comprised 65171 Kaiser
      Permanente Medical Care Program enrollees, aged 15 through 49 years, who
      completed questionnaires about smoking habits, including marijuana use, between
      1979 and 1985. Mortality follow-up was conducted through 1991. RESULTS: Compared
      with nonuse or experimentation (lifetime use six or fewer times), current
      marijuana use was not associated with a significantly increased risk of non
      acquired immunodeficiency syndrome (AIDS) mortality in men (relative risk [RR] =
      1.12, 95% confidence interval [CI] = 0.89, 1.39) or of total mortality in women
      (RR = 1.09, 95% CI = 0.80, 1.48). Current marijuana use was associated with
      increased risk of AIDS mortality in men (RR = 1.90, 95% CI = 1.33, 2.73), an
      association that probably was not causal but most likely represented uncontrolled
      confounding by male homosexual behavior. This interpretation was supported by the
      lack of association of marijuana use with AIDS mortality in men from a Kaiser
      Permanente AIDS database. Relative risks for ever use of marijuana were similar.
      CONCLUSIONS: Marijuana use in a prepaid health care-based study cohort had little
      effect on non-AIDS mortality in men and on total mortality in women.

PMID- 9146437
TI  - The effects of cigarette smoking and gestational weight change on birth outcomes
      in obese and normal-weight women.
AB  - OBJECTIVES: The associations of infant birth outcomes with maternal pregravid
      obesity, gestational weight gain, and prenatal cigarette smoking were examined.
      METHODS: A retrospective analysis of 1343 obese and normal-weight gravidas
      evaluated the associations of cigarette smoking, gestational weight change, and
      pregravid body mass index with birthweight, low birthweight, and small- and large
      for-gestational-age births. RESULTS: Smoking was associated with the delivery of
      lower-birthweight infants for both obese and normal-weight women, and gestational
      weight gain did not eliminate the birthweight-lowering effects of smoking. Women
      at highest risk of delivering lower-birthweight infants were obese smokers whose
      gestational gains were less than 7 kg and normal-weight smokers whose gestational
      gains were less than 11.5 kg. CONCLUSIONS: To balance the risks of small and
      large-size infants, gains of 7 to 11.5 kg for obese women and 11.5 to 16 kg for
      normal-weight women appear appropriate.

PMID- 9146438
TI  - Neighborhood social environments and the distribution of low birthweight in
      Chicago.
AB  - OBJECTIVES: This study examined the socioeconomic precursors of disparities in
      maternal health by measuring the associations of nine neighborhood-level
      indicators of social phenomena with low infant birthweight. METHODS: Vital
      records and census data for the Chicago metropolitan area in 1990 were merged (n
      = 112,327); a logistic regression model predicting low birthweight was estimated
      by backward elimination. RESULTS: With individual-level variables held constant,
      six neighborhood-level indicators predicted low birthweight, together
      contributing to a variation in rate of 5.5%. Community economic hardship and
      housing costs were positively associated with low birthweight, while community
      socioeconomic status, crowded housing, and high percentages of young and African
      American residents were negatively associated with low birthweight. CONCLUSIONS:
      Maternal health inequalities should be explored in the context of historical
      segregation, social stratification, the dynamics of social support, and resource
      sharing among communities. Several community characteristics associated with
      poverty are negatively associated with low birthweight. The traditional focus on
      individual risk factors for low birthweight limits our understanding.

PMID- 9146439
TI  - Mentally disordered women in jail: who receives services?
AB  - OBJECTIVES: Many jail inmates have severe psychiatric disorders (e.g.,
      schizophrenia, major affective disorders). The courts have mandated that
      detainees have a constitutional right to treatment. We investigated what
      proportion of female jail detainees needed mental health services, what
      proportion received services, and what variables predicted who received services.
      METHODS: Trained interviewers administered a psychiatric evaluation (the NIMH
      Diagnostic Interview Schedule) to 1272 randomly selected female jail detainees
      during jail intake in a large Midwestern city. Project staff then documented
      whether women subsequently received services, using records and case files.
      RESULTS: Of the women who needed services, 23.5% received them while they were in
      jail. Type of disorder, treatment history, and socio-demographic variables all
      affected the odds of a mentally ill woman's receiving services. CONCLUSIONS:
      Correctional health care is a growing national public health problem. The
      magnitude of mental health service needs far exceeds current resources.

PMID- 9146440
TI  - A dietary intervention in primary care practice: the Eating Patterns Study.
AB  - OBJECTIVES: This study evaluated the effectiveness of a low-intensity dietary
      intervention in primary care practice in lowering dietary fat intake and raising
      dietary fiber intake. METHODS: A randomized controlled trial of 28 physician
      practices in six primary care clinics enrolled, by telephone, adult patients who
      had appointments for nonurgent nonacute visits. Of 3490 eligible patients
      contacted, 2111 completed baseline interview; 86.1% also completed a 12-month
      follow-up. Physicians gave intervention participants a self-help booklet and a
      brief motivational message. Changes in fat and fiber from baseline to 12-month
      follow-up were evaluated. RESULTS: Intervention and control groups both reported
      a decrease in fat intake and an increase in fiber intake. The differential change
      and 95% confidence interval (CI) for the percentage of energy obtained from fat
      was -1.2 (CI = -0.71, -1.7) (P = .0015), for grams fiber/1000 kcal 0.32 (CI = 
      0.066, 0.71) (P = .086), for fat score -0.044 (CI = -0.016, -0.072) (P = .010),
      and for fiber score 0.036 (CI = 0.011, 0.061) (P = .014), with greater reductions
      in fat and greater increase in fiber in the intervention group. CONCLUSIONS: This
      low-intensity intervention was effective in dietary behavior change.

PMID- 9146441
TI  - Workplace conditions, socioeconomic status, and the risk of mortality and acute
      myocardial infarction: the Kuopio Ischemic Heart Disease Risk Factor Study.
AB  - OBJECTIVES: This study investigated whether the association between workplace
      conditions and the risk of all-cause and cardiovascular mortality and acute
      myocardial infarction differed by socioeconomic status. METHODS: Prospective data
      were used to examine these associations in 2297 Finnish men, with adjustment for
      prevalent diseases and biological, behavioral, and psychosocial covariates, and
      stratified by employment status and workplace social support. RESULTS: Elevated
      age-adjusted relative hazards for all-cause mortality were found for men who
      reported high demands, low resources, and low income; high demands, high
      resources, and low income; and low demands, high resources, and low income.
      Similar patterns were found for cardiovascular mortality. In contrast, elevated
      age-adjusted relative hazards for acute myocardial infarction were observed only
      in men who reported high demands, low resources, and low income. These results
      did not differ by level of workplace social support or employment status.
      CONCLUSIONS: The negative effects of workplace conditions on mortality and of
      myocardial infarction risk depended on income level and were largely mediated by
      known risk factors.

PMID- 9146442
TI  - Low blood pressure and five-year mortality in a Stockholm cohort of the very old:
      possible confounding by cognitive impairment and other factors.
AB  - OBJECTIVES: Low blood pressure has often been reported to be related to excess
      mortality in people over the age of 75 years. This study examined whether other
      predictors may account for the association. METHODS: A community-based cohort of
      1810 people who were aged 75 years and older was followed for 5 years. RESULTS:
      The relative risk of death was 1.39 (95% confidence interval [CI] = 1.11, 1.73)
      for people with systolic pressure lower than 130 mm Hg and 1.21 (95% CI = 1.02,
      1.43) for those with diastolic pressure lower than 75 mm Hg, compared with
      corresponding reference groups, when all other variables were simultaneously
      considered in Cox proportional hazards models. The observed association was
      present mainly in subjects with at least two of the three conditions
      (cardiovascular disease, limitation in activities of daily living, or cognitive
      impairment). The effect of low diastolic pressure on mortality was also
      significant in those with only cognitive impairment. CONCLUSIONS: Preexisting
      cardiovascular disease, limitation in activities of daily living, and, more
      important, cognitive impairment may be responsible for the association of low
      blood pressure with increased mortality in the very old in that they cause both
      reductions in blood pressure and excess deaths.

PMID- 9146443
TI  - Lifetime cocaine use and cardiovascular characteristics among young adults: the
      CARDIA study.
AB  - OBJECTIVES: Cocaine is a central nervous system stimulant associated with
      cardiovascular disease risk factors, morbidity, and mortality. Despite these
      demonstrated relationships, it has been difficult to assess the long-term
      cardiovascular consequences of cocaine use. METHODS: The Coronary Artery Risk
      Development in Young Adults study provides an opportunity to evaluate the
      association of lifetime cocaine use with cardiovascular disease risk factors in a
      randomly sampled biethnic cohort of men and women of varied socioeconomic status,
      aged 20 to 32 in 1987. RESULTS: More extensive cocaine use experience was
      associated with being White, older, and less educated, regardless of sex. Higher
      levels of licit and illicit substance use behavior were reported by those
      reporting more extensive cocaine experience; however, most cardiovascular disease
      risk factors such as systolic and diastolic blood pressure, heart rate,
      hypertension, physical activity, and anthropometric measurements were not related
      to lifetime cocaine experience. CONCLUSIONS: In this age group, the detrimental
      cardiovascular effects of cocaine may be limited to acute effects. Further
      studies are needed to determine whether continued exposure is related to
      cardiovascular disease risk factors later in life.

PMID- 9146446
TI  - Adolescent smokers' provision of tobacco to other adolescents.
AB  - OBJECTIVES: This study examined adolescent smokers provision of tobacco to other
      adolescents. METHODS: Data from a survey of 8th-, 9th-, and 10th-grade students
      in Minnesota were analyzed by using mixed-model logistic regression. RESULTS:
      More than two thirds (68.8%) of adolescent smokers had provided tobacco to
      another adolescent in the previous 30 days. Mother's smoking, number of friends
      who smoke, owning tobacco merchandise, number of cigarettes smoked in the past
      week, source of last cigarette (commercial), and recent attempt to buy cigarettes
      were associated with providing. CONCLUSIONS: The social availability of tobacco
      to youth needs further examination.

PMID- 9146444
TI  - Seven-year trends in body weight and associations with lifestyle and behavioral
      characteristics in black and white young adults: the CARDIA study.
AB  - OBJECTIVES: This study estimated the amount of weight change in a biracial cohort
      of young adults and the separate components attributable to time-related and
      aging-related changes, as well as identified possible determinants of weight
      change. METHODS: In this population-based prospective study of 18- to 30-year-old
      African-American and White men and women, body weight and prevalence of
      overweight were measured from 1985/86 to 1992/93. RESULTS: Average weight
      increased over the 7 years, increases ranging from 5.2 kg (SE = 0.2, n = 811) in
      White women to 8.5 kg (SE = 0.3, n = 882) in African-American women. Significant
      time-related increases in weight, ranging from 2.0 kg (SE = 1.0) in White women
      to 4.8 kg (SE = 1.0, n = 711) in African-American men, accounted for 40% to 60%
      of the average total weight gain. Aging-related increases were also significant,
      ranging from 2.6 kg (SE = 0.8, n = 944) in White men to 5.0 kg (SE = 1.1) in
      African-American women. The prevalence of overweight increased progressively in
      each group. Decreased physical fitness was most strongly associated with weight
      gain in both sexes. CONCLUSIONS: The observed dramatic time-related weight gains,
      most likely due to secular (period-related) trends, are a serious public health
      concern.

PMID- 9146445
TI  - Factors contributing to the hospitalization of patients with congestive heart
      failure.
AB  - OBJECTIVES: This study identifies acute precipitants of hospitalization and
      evaluates utilization of angiotension-converting enzyme inhibitors in patients
      admitted with congestive heart failure. METHODS: Cross-sectional chart-review
      study was done of 435 patients admitted nonelectively from February 1993 to
      February 1994 to an urban university hospital with a complaint of shortness of
      breath or fatigue and evidence of congestive heart failure. RESULTS: The most
      common identifiable abnormalities associated with clinical deterioration prior to
      admission were acute anginal chest pain (33%), respiratory infection (16%),
      uncontrolled hypertension with initial systolic blood pressure > or = 180 mm Hg
      (15%), atrial arrhythmia with heart rate > or = 120 (8%), and noncompliance with
      medications (15%) or diet (6%); in 34% of patients, no clear cause could be
      identified. After exclusion of those who were already on a different vasodilator
      or who had relative contraindications, 18 (32%) of the patients with ejection
      fractions < or = 0.35 measured prior to admission were not taking an angiotensin
      converting enzyme inhibitor on presentation to the hospital. CONCLUSIONS:
      Interventions to improve compliance, the control of hypertension, and the
      appropriate use of angiotensin-converting enzyme inhibitors may prevent many
      hospitalizations of heart-failure patients.

PMID- 9146447
TI  - Cigarette sales to African-American and white minors in low-income areas of
      Baltimore.
AB  - OBJECTIVES: This study documented illegal sales of cigarettes to minors in low
      income African-American and White urban areas in East Baltimore. METHODS: Six
      youths, aged 14 through 16 years, were sent to a random sample of 83 corner
      stores to attempt to purchase cigarettes. The youths provided the investigators
      with data on merchant, store, and purchase characteristics. RESULTS: The youths
      successfully purchased cigarettes in 85.5% of the stores; 58% of the stores
      displayed five or more cigarette advertisements outside their premises.
      CONCLUSIONS: Cigarette sales to minors and associated advertising remain
      prevalent in this urban community.

PMID- 9146448
TI  - The feasibility of a street-intercept survey method in an African-American
      community.
AB  - OBJECTIVES: This study evaluates the feasibility of a nonquota, street-intercept
      survey method that utilized random selection of interview sites. METHODS: The
      street-intercept survey was compared with a random digit-dial telephone survey
      conducted in the same catchment area among African-American adults aged 18 or
      older. RESULTS: The street-intercept survey's response rate was 80.2%; residence
      rate, 85.3%; interview completion rate, 97.9%; interference rate, 4.0%; and yield
      rate, 2.5 interviews per interviewer per hour. The street-intercept method
      produced more representative distributions of age and sex than the random-digit
      dial survey. CONCLUSIONS: The street-intercept method is a feasible alternative
      to traditional population survey methods and may provide better access to harder
      to-reach segments of the urban population in a safe manner.

PMID- 9146449
TI  - The effectiveness of a hospital-based program to promote exclusive breast-feeding
      among low-income women in Brazil.
AB  - OBJECTIVES: This study examined the effectiveness of a hospital program to
      promote exclusive breast-feeding in Santos, Brazil. METHODS: In a prospective
      design, women who delivered at a hospital with an active breast-feeding promotion
      program (n = 236) were compared with women who delivered at a nearby control
      hospital (n = 206). RESULTS: The two groups had similar demographic
      characteristics and previous breast-feeding histories. Exposure to breast-feeding
      activities, assessed by maternal recall prior to discharge, was universally high
      at the program hospital and universally low at the control hospital. Multivariate
      survival analysis showed that exclusive breast-feeding lasted 53 days longer
      among women who delivered at the program hospital. CONCLUSIONS: Hospital-based
      breast-feeding promotion programs may be effective in extending the duration of
      exclusive breast-feeding.

PMID- 9146450
TI  - Rural hospitals' experience with the National Practitioner Data Bank.
AB  - OBJECTIVES: This study examined hospital administrators' experiences with the
      National Practitioner Data Bank. METHODS: One hundred forty-nine rural hospital
      administrators completed questionnaires assessing their perceptions of the data
      bank. RESULTS: Nearly 90% of respondents rated the data bank as an important
      source of information for credentialing. Three percent indicated it had directly
      affected privileging decisions; 43% and 34%, respectively, believed the costs
      exceeded or equaled the benefits. Twenty percent reported changes that could
      decrease disciplinary action reports to the data bank. CONCLUSIONS: While the
      National Practitioner Data Bank is an important source of information to rural
      hospitals, it may, affect few credentialing decisions and motivate behavioral
      changes that could have a paradoxical effect on quality assurance.

PMID- 9146451
TI  - The effectiveness of family planning programs evaluated with true experimental
      designs.
AB  - OBJECTIVES: This paper describes the magnitude of effects for family planning
      programs evaluated with true experimental designs. METHODS: Studies that used
      true experimental designs to evaluate family planning programs were identified
      and their results subjected to meta-analysis. RESULTS: For the 14 studies with
      the information needed to calculate effect size, the Pearson r between program
      and effect variables ranged from -.08 to .09 and averaged .08. CONCLUSIONS: The
      programs evaluated in the studies considered have had, on average, smaller
      effects than many would assume and desire.

PMID- 9146452
TI  - Exercise and depression in midlife: a prospective study.
AB  - OBJECTIVES: This study examined the relationship of self-reported physical
      activity with subsequent depression and psychiatric distress. METHODS: Physical
      activity was assessed in medical school and midlife in 973 physicians as part of
      a prospective observational study. Outcome measures were the incidence of self
      reported clinical depression and psychiatric distress on the General Health
      Questionnaire. RESULTS: The risk of depression was similar for nonexercisers and
      exercisers. No relationship was observed between physical activity level and
      subsequent psychiatric distress. CONCLUSIONS: This study found no evidence that
      exercise reduces risk for depression or psychiatric distress.

PMID- 9146453
TI  - Composite cardiovascular risk outcomes of a work-site intervention trial.
AB  - OBJECTIVES: Two composite outcome measures were used to assess the efficacy of
      work-site risk factor interventions: the Framingham multiple logistic function
      and a standardized composite equation that was an unweighted combination of risk
      factors. METHODS: Twenty-eight work sites in Sydney, Australia, were randomly
      assigned to health risk assessment, risk factor education, behavioral counseling,
      or behavioral counseling plus incentives. RESULTS: Over 12 months, scores on the
      multiple logistic function increased for the behavioral counseling plus
      incentives condition relative to the other conditions. Standardized scores
      decreased for behavioral counseling relative to the incentive condition and the
      average of all other conditions. CONCLUSIONS: Behavioral counseling produces
      larger changes in the life-style behaviors contributing to coronary heart disease
      risk than other commonly used interventions.

PMID- 9146454
TI  - Hysterectomy, oophorectomy, and heart disease risk factors in older women.
AB  - OBJECTIVES: This study examined the relation of hysterectomy and oophorectomy to
      heart disease risk factors. METHODS: Data were collected and analyzed for 1150
      women aged 50 through 89. RESULTS: Of these women, 21.8% reported hysterectomy
      with bilateral oophorectomy; 22.1%, hysterectomy with ovarian conservation.
      Compared with women without hysterectomy, oophorectomized women, especially those
      20 or more years postmenopause, had increased lipids, lipoproteins, glucose, and
      insulin; blood pressures were increased among current estrogen users. Women with
      hysterectomies with ovarian conservation had similar or more favorable risk
      factors than nonhysterectomized women. CONCLUSIONS: Bilateral oophorectomy, but
      not hysterectomy, may have long-term negative consequences for heart disease risk
      factors not totally ameliorated by estrogen use.

PMID- 9146455
TI  - The case of the missing secretary: DHEW's failed efforts to create a Cabinet
      secretary of health.
AB  - In response to professional and political pressures in 1967, an incident occurred
      at the Department of Health, Education, and Welfare that illustrates the delicacy
      and complexity of the legislative process. In an effort to bypass interest group
      influences, the undersecretary of the Department undertook a maneuver that
      backfired and frustrated an opportunity that might have resulted in the
      establishment of a Cabinet office of Health. In addition to demonstrating the
      sensitivity of the legislative process, and the dangers of overconfidence in
      dealing with the process, the events also offer moral guidance: too stubborn,
      idealistic convictions of good people, however well intentioned the actions, may
      serve to defeat the desired ends.

PMID- 9146456
TI  - Underestimating cocaine use during pregnancy.

PMID- 9146457
TI  - Asbestos-related cancer and the amphibole hypothesis. The first documentation of
      the association.

PMID- 9146458
TI  - Asbestos-related cancer and the amphibole hypothesis. The amphibole hypothesis:
      neither gone nor forgotten.

PMID- 9146459
TI  - Asbestos-related cancer and the amphibole hypothesis. The hypothesis is still
      supported by scientists and scientific data.

PMID- 9146460
TI  - Integrating HIV prevention, STD, and family planning services. The availability
      of HIV services at different types of clinics: a survey.

PMID- 9146461
TI  - Integrating HIV prevention, STD, and family planning services. Comprehensive
      efforts in Philadelphia.

PMID- 9146462
TI  - Integrating HIV prevention, STD, and family planning services. A sexual and
      reproductive health approach in Latin America and the Caribbean.

PMID- 9146463
TI  - Integrating HIV prevention, STD, and family planning services. The need for
      integrated government funding and services.

PMID- 9146464
TI  - Requesting diagnostic imaging examinations: a position paper of the Canadian
      Association of Radiologists.

PMID- 9146465
TI  - Dying or flying? Strategies for riding the curves of change.

PMID- 9146466
TI  - Adenomyoma of the common bile duct imaged with endoscopic ultrasonography: case
      report.

PMID- 9146467
TI  - High-flow priapism--recurrence after initially successful selective coil
      embolization: case report.

PMID- 9146468
TI  - Peripheral magnetic resonance angiography: review of techniques, indications and
      artifacts.

PMID- 9146469
TI  - Radiologic diagnosis and management of uterine artery pseudoaneurysm: case
      report.

PMID- 9146470
TI  - The timing of computed tomography in acute stroke: a practice audit.
AB  - OBJECTIVE: To compare the patterns of practice and diagnostic yields for early
      and late computed tomography (CT) in patients with acute stroke. PATIENTS AND
      METHODS: Among the 191 consecutive patients with acute stroke admitted to a
      university teaching hospital from Sept. 1, 1989, to Sept. 1, 1993, charts were
      available for review for 185. In addition to the timing and results of CT in
      these patients, data were collected on the demographic features of the patient
      group and the presence of any cardiovascular risk factors or other features
      suggestive of a nonstroke cause for the neurologic deficit. RESULTS: Of the 185
      patients for whom charts were available, 177 (95.7%) underwent CT. In 107 (60.4%)
      of the cases, scanning was performed early, within 24 hours of the onset of
      neurologic deficit, and only 25 (23.4%) of these scans demonstrated a lesion. Of
      the 70 initial scans obtained more than 24 hours after the deficit onset (delayed
      scanning), 41 (58%) revealed a diagnostic lesion (relative probability of finding
      a lesion with early vs delayed scanning, 0.40; 95% confidence interval 0.27 to
      0.59; p < 0.0001, Fisher's exact test). Of the 107 patients who underwent early
      scanning, 45 (42.0%) underwent repeat CT, and previously unrecognized lesions
      were seen in 28 (62%) of these. Scanning was repeated in only 17 (24%) of the 70
      patients who underwent delayed initial scanning (p = 0.02), and previously
      unrecognized lesions were seen in only 4 of these (24%). All lesions documented
      on repeat scans after initially nondiagnostic scanning were ischemic. Patients
      presenting with features thought to justify early CT were no more likely to
      undergo this intervention than those without such features (68% and 56%
      respectively, p = 0.11). CONCLUSIONS: Initial CT was often carried out within 24
      hours of the onset of deficit in patients with suspected acute stroke at this
      institution, CT was a low-yield investigation, and scanning was frequently
      repeated. Although the literature suggests that clinical features can distinguish
      that subset of patients who should undergo urgent neuroimaging, prospective
      studies are needed to establish the indications for early CT in patients
      presenting with acute neurologic deficit.

PMID- 9146471
TI  - Residents' corner. Answer to case of the month #46. Torsion and infarction of the
      greater omentum.

PMID- 9146472
TI  - Residents' corner. Answer to case of the month #47. Neurocysticercosis.

PMID- 9146473
TI  - Ethical issues in interventional radiology.

PMID- 9146474
TI  - Tuberculosis. Part II.

PMID- 9146475
TI  - Modality-specific organization for cutaneous and proprioceptive sense in human
      primary sensory cortex studied by chronic epicortical recording.
AB  - Modality specificity of human primary somatosensory cortex was studied by
      recording somatosensory evoked potentials (SEPs) from subdural electrodes in a
      patient with intractable focal motor seizure. A newly developed device was used
      for selectively activating proprioception. The spatial and temporal distributions
      of proprioception-related SEPs elicited by brisk passive flexion movement at the
      proximal interphalangeal (PIP) joint of the middle finger (4 degrees in 25 ms)
      were quite different from those to cutaneous sense evoked by electric stimulation
      of the digital nerve at the same site. It was for the first time demonstrated
      that proprioception-related SEPs following passive finger movement do not
      originate in area 3b, which was clearly activated by cutaneous stimulation, and
      that other sites at the sensorimotor cortex such as areas 2, 3a and 4 possibly
      contribute to the cortical processing of proprioception.

PMID- 9146476
TI  - Enhanced amplitude reduction of somatosensory evoked potentials by voluntary
      movement in the elderly.
AB  - We studied the effects of aging on modification of the median nerve somatosensory
      evoked potentials (SEPs) by voluntary movement in 17 aged (66.5 +/- 8.9 years,
      mean +/- SD) and 12 young normal humans (27.5 +/- 5.0 years). The amplitudes of
      cortical SEP components were generally larger in the aged group than in the young
      group. Following isometric contraction of the thenar muscle, the aged group
      showed significant attenuation of the prerolandic P22-N28-P45 and the
      postrolandic P24-N30-P45, while the young group only demonstrated significant
      reduction of the prerolandic P22-N28 amplitude. In the prerolandic N28-P45 and
      the postrolandic P24-N30 and N30-P45, amplitudes reduced by voluntary movement
      (gated amplitude) significantly correlated with amplitudes at rest (resting
      amplitude) and with the age of subjects. The effects of stimulus intensity and
      frequency on gating supported the correlative changes between gated and resting
      amplitudes. These results suggest that the magnitude of gating depends on SEP
      amplitudes at rest, and that augmented gating in the aged group is a result of
      enlarged SEPs. Since the cervical and Erb's potentials were not changed by
      movement, and passive movement did not significantly affect the SEPs, a
      centrifugal mechanism is probably responsible for gating in this study.

PMID- 9146477
TI  - The usefulness of the spinal and subcortical components of the posterior tibial
      nerve SEPs for spinal cord monitoring during aortic coarctation repair.
AB  - This study examines how the recording of the lumbar and subcortical components of
      the posterior tibial nerve (PTN) SEPs may usefully replace that of cortical
      components in situations in which these components cannot be reliably obtained
      (infants, high concentrations of halogenated gasses). Lumbar, brain-stem, and
      cortical PTN SEPs were intraoperatively monitored in 7 patients undergoing repair
      of aortic coarctation under variable isoflurane concentration (up to 1.2%). Four
      patients were less than 1 year old. Two distinct activities were evidenced at the
      lumbar level in all of the patients: the dorsal root component (DRC) and the
      dorsal horn negativity (DHN). The equivalent of the adult P30 (lemniscal
      positivity; LP) was also present in all of the patients, whatever their age or
      the concentration of isoflurane. By contrast, the parietal activities were absent
      intraoperatively in the youngest patients. Spinal-cord ischemia consecutive to
      aortic cross-clamping gave rise to early DHN changes and later alterations of the
      LP in the two patients in which it occurred, while the DRC and the peripheral
      nerve activities remained unchanged. This elective sensitivity of the DHN is
      likely due to it being dependent on the gray matter of the spinal cord, the basal
      metabolism of which is greater than that of the white matter and to the situation
      of the DHN generator in a watershed zone of the spinal cord. This study
      emphasizes the interest of PTN SEPs for spinal-cord monitoring in vascular
      surgery and the importance of combining the recording of parietal activities with
      that of the lumbar spinal components.

PMID- 9146478
TI  - The pathophysiology of giant SEPs in cortical myoclonus: a scalp topography and
      dipolar source modelling study.
AB  - Somatosensory evoked potential (SEP) recordings in patients suffering from
      cortical myoclonus (CM) are characterised by evidence of abnormally enhanced
      scalp components. Our aim was to verify whether enhanced activity in giant SEPs
      arises from the same generators as in healthy subjects. We used the brain
      electrical source analysis (BESA) to compare scalp SEP generators of healthy
      subjects to those calculated in 3 patients with CM of varying causes. Firstly, we
      built a 4-dipole model explaining scalp distribution of early SEPs in normal
      subjects and then applied it to traces recorded from CM patients. Our model,
      issued from the right median nerve grand average and applied also to recordings
      from single individuals, included a dipole at the base of the skull and three
      other perirolandic dipoles. The first of the latter dipoles was tangentially
      oriented and was active at the same latencies as the N20/P20 potentials and, with
      opposite polarity, the P24/ N24 responses; the second dipole explained the
      central P22 distribution and the third had a peak of activity corresponding to
      the N30 component. When we applied our 4-dipole model to CM recordings, the first
      perirolandic dipole had a third peak of activity in all patients at the same
      latency as a parietal negativity and a frontal positivity, both following giant
      P24/N24 components; on the other hand, in one patient the second perirolandic
      dipole showed a later activation corresponding to a high central negativity,
      following a giant P22 response. We suggest that only the initial giant SEPs
      correspond to physiological potentials evoked in healthy subjects. The occurrence
      of late giant SEPs could be explained by hyperpolarization, following the
      postsynaptic excitatory potentials responsible for the early giant components.

PMID- 9146479
TI  - Somatosensory evoked potentials in adults with cortical dysgenesis and epilepsy.
AB  - Cortical dysgenesis (CD) is a well-recognised cause of epilepsy, but its
      functional anatomy is not fully understood. We recorded cortical somatosensory
      evoked potentials (SEPs) in 13 adult patients with epilepsy and various CDs
      excluding diffuse gyral malformations as diagnosed by MRI. The CD involved the
      perirolandic/perisylvian region in 7 patients. Six patients had neurological
      signs but only 3 had sensory dysfunction (astereognosis). As compared with 12
      control subjects, SEPs were considered definitely abnormal in 7 patients
      (including the 6 with neurological signs) and equivocally abnormal in 2. The
      abnormalities ranged from defects affecting single components to absence of all
      potentials of cortical origin in one patient with hemiparesis and astereognosis.
      In this case it appears that gross sensory function must have been mediated by
      subcortical structures or through diffuse cortical projections. The initial
      cortical potentials (N20/P20) were absent in 6 patients, 5 of whom had CD in
      zones involving or bordering on the primary sensory cortex. Parietal potentials
      following N20 were absent or attenuated in 4 patients and of abnormally wide
      distribution, spreading to frontal, midline and ipsilateral electrodes, in 3
      frontal components following P20 were absent, attenuated, delayed or distorted by
      abnormal spread of the parietal activity in 5 patients. Five patients with
      unilateral CD showed definite or equivocal SEP abnormalities to stimulation of
      both arms, suggesting there may be more widespread disturbance of cortical
      organisation and/or synaptogenesis, beyond the resolution of present day
      neuroimaging.

PMID- 9146480
TI  - Integrated mismatch negativity (MMNi): a noise-free representation of evoked
      responses allowing single-point distribution-free statistical tests.
AB  - If the repeated presentation of a single (standard) auditory stimulus is randomly
      interspersed with a second acoustically different (deviant) stimulus, the
      cortical activity evoked by the deviant stimulus can contain a negative component
      known as the mismatch negativity (MMN). The MMN is derived by subtracting the
      averaged response evoked by the standard stimulus from that evoked by the deviant
      stimulus. When the magnitude of the response is small or the signal-to-noise
      ratio is poor, it is difficult to judge the presence or absence of the MMN simply
      by visual inspection, and statistical detection techniques become necessary. A
      method of analysis is proposed to quantify the magnitude and statistically
      evaluate the presence of the MMN based on time-integrated evoked responses. This
      paper demonstrates the use of this integrated mismatch negativity (MMNi) analysis
      to detect the MMN evoked by stimulus contrasts near the perceptual threshold of
      two subjects. The MMNi, by virtue of being equivalent to a low-pass filtered
      response, presents an almost noise-free estimate of MMN magnitude. A single
      measure of the integrated evoked response at a fixed time point is used in a
      distribution-free statistic that compares the magnitude of the averaged response
      evoked by the deviant stimulus with a magnitude distribution derived from 200
      subaveraged responses to the standard stimulus (with the number of sweeps per
      average equal to that of the deviant stimulus). This allows a calculation of the
      exact probability for the null hypothesis that the negative magnitude of the
      response evoked by the deviant stimulus is drawn from the magnitude distribution
      of responses evoked by the standard stimulus. Rejection of this hypothesis
      provides objective evidence of the presence of the MMN.

PMID- 9146481
TI  - Robust moving averages, with Hopfield neural network implementation, for
      monitoring evoked potential signals.
AB  - This technical note describes a robust version of moving averages, that enables
      reliable monitoring of the evoked potential (EP) signals. A cluster analysis (CA)
      procedure is introduced to robustify the signal averaging (SA). It is implemented
      via a Hopfield neural network (HNN), which performs selection of the trials
      forming a cluster around the current state of the EP signal. The core of this
      cluster serves as an estimate of the instantaneous EP. The effectiveness of the
      method, indicated by application to real data, and its computation efficiency,
      due to the use of simple matrix operations, makes it very promising for clinical
      observations.

PMID- 9146483
TI  - Prognostic value of visual evoked potentials (VEP) in infants with visual
      inattentiveness.
AB  - Visual evoked potentials elicited by strobe flash (fVEPs) were recorded in 56
      infants (3 months to 15 months of age) with visual inattentiveness but without
      prechiasmal problems. Their visual status was reexamined one or more years later
      when 41 children were found to be visually competent (Group NB) and 15 were blind
      (Group B). We also evaluated a group of 32 age-matched children who had no visual
      symptoms (Group C). It was found that well organized VEP waveforms over one or
      both hemispheres (Types U and S), or those with a characteristic negative shift
      (Type N) suggest favorable prognosis. Integrated voltage of the VEP correlated
      well with long-term prognosis for visual recovery. The vertex VEP also (had)
      provided some predictions for visual prognosis. Overall results indicate good
      prognosis if related to sufficient voltage and complexity of the VEP components.

PMID- 9146482
TI  - A comparison of the repetitive click and conditioning-testing P50 paradigms.
AB  - The auditory P50 ERP component has previously been studied either in the
      repetitive click or the conditioning-testing (C-T) paradigm. For 20 subjects, we
      compared 4 repetitive click and 4 C-T protocols in a single experimental session
      with identical recording techniques and with interclick intervals comparable to
      the C-T intervals. In the C-T protocols, a long interval between click pairs
      ensured full recovery of P50 to the C click. The analysis of P50 topographies
      provided strong evidence that the same component was measured in the two
      paradigms. For both paradigms, P50 amplitude was progressively suppressed as the
      interclick or C-T interval decreased (P < 0.0001), with parallel interval vs. P50
      amplitude regression lines for the two paradigms. There was a strong trend (P =
      0.08) for the repetitive click amplitudes to be smaller than T amplitudes for
      comparable repetitive click and C-T intervals. Equivalently, this strong trend
      suggests that repetitive click intervals must be longer (by about 300 ms) than
      the C-T interval to generate equivalent amplitude P50 responses. We conclude that
      the same component is measured in both paradigms, that P50 amplitude decreases
      with decreasing interstimulus intervals in both paradigms, and that in normals,
      for comparable inter-click and C-T intervals, there is greater P50 suppression in
      the repetitive click paradigm. Finally, we note that the comparison of paradigms
      within normals does not necessarily apply to clinical samples.

PMID- 9146484
TI  - Electrophysiological assessment of visual function in IDDM patients.
AB  - Various electrophysiological tests have been employed to reveal functional
      abnormalities at different levels of the visual system in insulin-dependent
      diabetic (IDDM) patients. The aim of our work was to assess, with a comprehensive
      neurophysiological protocol evaluating the retinal, macular and visual pathways
      functions, whether and when such electrophysiological abnormalities do appear in
      IDDM patients free of any fluorangiographic sign of retinopathy with various
      disease duration. Flash-electroretinogram (ERG), oscillatory potentials (OPs),
      pattern-electroretinogram (PERG), and visual evoked potentials (VEPs) in basal
      condition and after photostress were assessed in 12 control subjects (C) and 42
      aged-matched IDDM patients without clinical retinopathy (DR-) divided, on the
      basis of the disease duration, into 4 groups (1-5, 6-10, 11-15, 16-20 years). In
      addition another age-matched group of IDDM patients with a background retinopathy
      (DR+; n = 12; duration of disease 18 +/- 49 years) was evaluated. In all IDDM DR
      patients PERG and VEP were significantly impaired. In addition, groups 11-15 and
      16-20 years displayed impaired OPs. All electrophysiological parameters were
      further impaired in DR+ patients. In conclusion, retinal, macular and visual
      pathways functions are differently impaired in IDDM (DR-) patients with different
      disease duration. Electrophysiological impairment starts in the nervous
      conduction of the visual pathways with an early involvement, goes on in the
      innermost retinal layers and in the macula and ends in the middle and outer
      retinal layers.

PMID- 9146485
TI  - The effects of electroconvulsive shock on the flash visual evoked potential in
      the rat.
AB  - The effects of electroconvulsive shock (ECS) on the flash visual evoked potential
      (FVEP) were studied in the awake albino rat. Immediately after the induction of
      generalised seizure activity, the FVEP was totally abolished although
      accidentally averaged rhythmic epileptiform activity was often present in the
      trace. During the second recording, a potential had reappeared but this response
      was suspected of being a superior colliculus FVEP masquerading as a cortical
      response. By the third recording, the genuine cortical FVEP had returned, albert
      with an abnormally large amplitude. The waveform subsequently remained
      significantly distorted although it had regained an approximately normal
      morphology within 6-7 min of the administration of ECS. It was not possible to
      identify the principal site of action of ECS but it was concluded that ECS may
      impact on activity generated at more than one location within the optic pathways.
      The present findings are compared with a number of previous animal and human
      studies where the FVEP was apparently preserved following ECS and attempts are
      made to explain the discrepancy in results. The relevance of the present findings
      for understanding the pathophysiology of electrical stunning and of the loss or
      impairment of consciousness during generalised epileptic seizures is also
      discussed.

PMID- 9146486
TI  - Inverse localization of electric dipole current sources in finite element models
      of the human head.
AB  - The paper describes finite element related procedures for inverse localization of
      multiple sources in realistically shaped head models. Dipole sources are modeled
      by placing proper monopole sources on neighboring nodes. Lead field operators are
      established for dipole sources. Two different strategies for the solution of
      inverse problems, namely combinatorial optimization techniques and regularization
      methods are discussed and applied to visually evoked potentials, for which
      exemplary results are shown. Most of the procedures described are fully automatic
      and require only proper input preparation. The overall work for the example
      presented (from EEG recording to visual inspection of the results) can be
      performed in roughly a week, most of which is waiting time for the computation of
      the lead field matrix or inverse calculations on a standard and affordable
      engineering workstation.

PMID- 9146487
TI  - Evolution of cerebral edema and its relationship with power in the theta band.
AB  - In previous papers we have proposed that in patients with space-occupying
      lesions, delta power was related with the volume of the lesion and theta power
      with the volume of the edema. In this report we analyze the evolution of 10
      patients with space-occupying lesions in whom we measured the volume of the
      lesion and of the edema before and after treatment that produced changes in these
      volumes. EEGs were recorded in the leads of the 10-20 system referenced to linked
      earlobes. Delta and theta powers were calculated for voltage and current source
      densities (CSD) and compared with age-norms to compute conventional Z-maps. These
      maps provide probability statements about the deviation of observed values from
      the norm. Rank correlations between the change in the volume of the lesion before
      and after treatment and the change in Z-values before and after treatment were
      significant only in the delta band. However, rank correlations between the change
      in the volume of the edema and the change in EEG Z-values were only significant
      in the theta band. These correlations were higher for CSD than for voltage
      estimates. We also observed that the site of the lesion and of the edema was
      better represented by CSD maps than by voltage maps. These results are also in
      agreement with our previous reports, in which we observed more precise
      localization of brain lesions by CSD than by voltage estimates.

PMID- 9146488
TI  - Intra-hemispheric alpha coherence decreases with increasing cognitive impairment
      in HIV patients.
AB  - Inter-hemispheric and intra-hemispheric canonical coherences in the alpha range
      between EEG signals collected from frontal and posterior groups of electrodes
      were estimated for 38 HIV positive subjects and 23 uninfected controls.
      Neuropsychological testing was used to categorize the degree of cognitive
      impairment evident in each of the subjects. A linear regression analysis provided
      evidence that intra-hemispheric coherence decreased with increasing cognitive
      impairment in impaired HIV+ subjects, as measured by a Global Impairment Score
      (GIS). There was no evidence that cognitively unimpaired HIV+ subjects differed
      in coherence when compared to uninfected control subjects. Severely impaired HIV+
      subjects showed significantly decreased coherence compared to uninfected
      controls. These data contradict previous work demonstrating increased intra
      hemispheric and inter-hemispheric alpha coherence in impaired HIV subjects. In
      addition, they provide evidence that intra-hemispheric (and possibly inter
      hemispheric) disconnection is associated with cognitive impairment in HIV.

PMID- 9146489
TI  - Periodic lateralized epileptiform discharges (PLEDs) following stroke are
      associated with metabolic abnormalities.
AB  - PLEDs are an electroencephalographic phenomenon consisting of high voltage
      stereotyped periodic transients distributed over one hemisphere, associated with
      acute or subacute structural lesions as well as with metabolic abnormalities. We
      have evaluated the contribution of metabolic factors in patients with acute
      hemispheric stroke. Temperature, serum electrolytes, glucose, kidney and liver
      function tests were examined in two groups of 14 patients each following acute
      hemispheric stroke differing in regard to the appearance of PLEDs in the EEG. CT
      features of the infarcts were also compared. Patients with PLEDs had more
      metabolic derangements as compared to patients with no PLEDs (Mann-Whitney
      ranking test P = 0.01). Hyperglycemia and fever were significantly associated
      with PLEDs (logistic regression model, P < 0.05). There was no significant
      difference regarding radiological findings between the two groups. We conclude
      that acute stroke as a structural lesion predisposes to PLEDs but the latter may
      be triggered by metabolic disturbances, mainly hyperglycemia and fever.

PMID- 9146490
TI  - Angelman's syndrome: clinical and electroencephalographic findings.
AB  - Angelman's syndrome is a rare genetic disorder characterized by developmental
      delay, craniofacial abnormalities, ataxia, paroxysmal laughter, and seizures. The
      diagnosis is suspected in infants who have the characteristic clinical features
      and electroencephalographic (EEG) abnormalities and is confirmed by the genetic
      identification of a maternally derived 15q11-13 deletion. We report on 3 patients
      with genetically confirmed Angelman's syndrome who had the characteristic
      clinical and EEG features. The EEGs demonstrated high-amplitude 2- to 3-Hz delta
      activity, with intermittent spike-and-slow-wave discharges maximal in the
      occipital region in 2 patients and generalized sharp-and-slow-wave discharges,
      occipital spikes, and electrographic status epilepticus during slow-wave sleep in
      the other patient. The findings of generalized high-amplitude delta slowing and
      occipital spike-and-wave discharges, facilitated by eye closure, in children with
      developmental delay and seizures suggest the diagnosis of Angelman's syndrome and
      should lead to genetic testing.

PMID- 9146491
TI  - Olfactory event-related potentials to amyl acetate in congenital anosmia.
AB  - Olfactory function was evaluated by olfactory event-related potentials and
      standardized psychophysical measures including the Smell Identification Test and
      odor detection threshold tests for 3 chemosensory stimulants in 9 subjects with
      isolated congenital anosmia and 9 age- and gender-matched normosmic controls.
      There was a significant difference in Smell Identification Test scores (P <
      0.001) and odor detection thresholds for phenylethyl alcohol (P < 0.001) and
      isoamyl acetate (P < 0.001) between the anosmic and normosmic subjects. Detection
      thresholds for chloracetyl phenone, a trigeminal stimulant, did not differ
      between the 2 groups. Olfactory evoked potentials were recorded in response to
      amyl acetate and air control stimuli presented at volume flow rate of 5 l/min,
      stimulus duration of 40 ms, and randomized interstimulus intervals of 6-30 s. In
      the control subjects, evoked potentials to amyl acetate were characterized by 4
      reproducible components (P1, N1, P2, and N2). In the subjects with congenital
      anosmia, no reproducible evoked potential components were identified in response
      to amyl acetate. No reproducible evoked potential components were seen in
      response to the air control stimulus in either the anosmic or normosmic groups.
      These data suggest that olfactory evoked potentials provide a specific measure of
      olfactory function.

PMID- 9146493
TI  - On the existence of different types of central beta rhythms below 30 Hz.
AB  - EEGs were recorded from sensorimotor areas of 12 subjects performing unilateral
      self-paced brisk and slow finger movements. Two different beta components were
      found below 30 Hz: (i) One component, at about twice the frequency of the mu
      rhythm, showed desynchronization in parallel with the mu rhythm starting at about
      2 s prior to movement. Measurements of bicoherence have shown that this beta
      component can be non-linearly related to the arch-shaped mu rhythm. (ii) Another
      beta component started to desynchronize about 1 s prior to movement, recovered
      very fast and displayed a pronounced post-movement beta synchronization (PMBS)
      within the first second after movement-offset. This PMBS was found in the
      frequency band between 12 and 26 Hz. The average percentage power increase at
      contralateral sensorimotor area was 232% (SD = 82%) for brisk and 265% (SD =
      102%) for slow movements. The PMBS was of contralateral dominance and is
      interpreted as a correlate of active inhibition or idling of the primary motor
      area following movement execution.

PMID- 9146492
TI  - Cardiac field effects on the EEG.
AB  - The electrical field of the heart propagates throughout the entire body and
      causes changes in the surface potentials on the scalp that are superimposed on
      brain electric signals. When heart cycle-related EEG averaging is performed, e.g.
      in order to measure heart cycle-related brain potentials, the effects of the
      cardiac electrical field result in a high-amplitude artifact in the surface
      potentials. The topographic and temporal distributions of the cardiac field
      artifact were measured in 9 normal subjects. In addition, the effects of head
      turning on the field were investigated. The electrocardiac artifact is most
      prominent during the QRS complex and during the T wave of the heart cycle. In
      both cases it is distinctly asymmetrical in relation to the hemispheres. A
      comparison of the scalp potentials and a computed vector ECG showed the 3
      dimensional nature of the artifact. Non-computational strategies for the handling
      of the ECG artifact are discussed. A proper separation of the effects of the
      cardiac electrical field from heart cycle-related brain potentials is a
      prerequisite for the study of heart cycle-coordinated brain potentials.

PMID- 9146494
TI  - The resolution-field concept.
AB  - The concept of a resolution field provides a means to compare arbitrary
      estimators of a brain activity of interest (AOI), represented, for example, by
      the amplitude of a dipole at a certain location of interest with well-defined and
      known direction. Like the lead field, it represents a vector field with the
      property that a measure of the impact of a hypothetical dipole at an arbitrary
      point in the brain is obtained by calculating the scalar product with the
      respective dipole moment. While in the case of the lead field this measure of
      impact quantifies the contribution of a hypothetical dipole to the data recorded
      in a specific measurement channel, in the case of the resolution field it
      quantifies the contribution of a hypothetical dipole to the estimate of the AOI.
      The resolution-field concept, which uses elements of the Backus-Gilbert theory
      and is closely related to the concept of a resolution matrix, is illustrated with
      examples based on a simulated measurement with a 148-channel magnetometer system.

PMID- 9146495
TI  - 3D localization of surface 10-20 EEG electrodes on high resolution anatomical MR
      images.
AB  - A method to visualize surface EEG electrodes on conventional high-resolution
      magnetic resonance (MR) images is presented. Because conventional silver or gold
      electrodes generate an insignificant artifactual signal signature in MR images, a
      plastic capsule filled with gadolinium-doped water was designed to mold onto each
      electrode, thereby outlining the electrode surfaces as a negative imprint on MR
      images. MR images of the head with capsules affixed clearly demonstrated the
      location and shape of the electrodes. Selected cranial tissues were identified by
      using semi-automatic image segmentation to determine their three-dimensional
      spatial relationship to the electrodes. Such representations could be used as a
      starting point for more precise EEG source localization modeling applicable to
      individual patients.

PMID- 9146496
TI  - Effects of nitrous oxide on electrocorticography during epilepsy surgery.
AB  - Interictal spikes on intraoperative electrocorticography during epilepsy are used
      to tailor resections. There have been a few systematic quantitative studies of
      anesthetic effects on these interictal discharges, and none on the effects of
      nitrous oxide (N2O). We calculated spike rates on ECoG on and off N2O in 18
      epilepsy surgery patients with subdural strips and grids, analyzing the most
      active recording contract. In a blinded analyses ten patients had fewer spikes on
      N2O, while eight patients had more spikes on N2O. The mean spike rates did not
      differ (41/min on N2O and 40/min off N2O). Spike rate on and off N2O were
      compared using the non-parametric Wilcoxon matched pairs test. These rates were
      not significantly different. Our study indicates that N2O in doses employed dose
      not effect interictal spikes and this agent may be used during epilepsy surgery
      without concerns about suppression of epileptiform activity.

PMID- 9146497
TI  - Estimating cortical activity from VEPS with the shrinking ellipsoid inverse.
AB  - An iterative inverse method using Tikhonov regularization (the shrinking
      ellipsoid method) previously tested in a model system is used to invert the
      sequence of bioelectric scalp fields evoked by the onset of a checkerboard
      pattern in either the right or left lower hemifield. The shrinking ellipsoid
      method is modified from its original description to accommodate simultaneously
      inverting a sequence of thirteen VEP scalp fields measured from 65 to 125 ms
      after stimulus onset. This allows the evoked cortical activity to be tracked in 5
      ms intervals without distortion due to occasional VEP scalp fields in the
      sequence that have too low a signal-to-noise ratio to be reliably inverted in
      isolation. A new method is described to identify the surface of the cortex from
      MRI data. This is required to implement the shrinking ellipsoid inverse. Results
      from two subjects studied in detail are presented. The earliest cortical activity
      occurs either in area MT (the middle temporal area) or simultaneously in MT and
      striate cortex (V1). However when it does occur in both areas, the activity in V1
      is relatively weak and quickly subsides. Seventy-five ms after stimulus onset
      activity is seen mainly near MT corresponding to a region identified from PET
      studies as one that subserves motion processing. Activity moves to V1 by 90-100
      ms after stimulus onset. Near 120 ms after stimulus onset, cortical activity
      returns to the region near MT. Virtually all activity identified in this time
      epoch occurs in the cortical hemisphere contralateral to the location of the
      stimulus in the visual field.

PMID- 9146498
TI  - Cortical potentials preceding pro- and antisaccades in man.
AB  - The antisaccade task has been used widely to assess a frontal lobe deficit. In
      the present study cortical potentials preceding prosaccades and antisaccades were
      recorded in 7 healthy subjects with 19 scalp electrodes according to the
      international 10-20 system. The main results were as follows: (1) In both saccade
      types, a slow presaccadic negative shift was observed at dorso-medial frontal
      recording sites. The integral over these potentials was significantly greater for
      antisaccades at the C3, C4 and Cz location than in prosaccades. (2) The integral
      over presaccadic positivity was significantly lower for antisaccades compared
      with prosaccades at the Cz location. It is concluded that these results support
      an important role of the supplementary eye fields in generating antisaccades.

PMID- 9146499
TI  - Precursors of the evoked K-complex in event-related brain potentials in stage 2
      sleep.
AB  - The aim of the study was to examine precursors of the evoked K-complex as
      manifested in event-related brain potentials (ERPs) during stage 2 sleep. ERPs to
      infrequent deviant tones of 1100 and 2000 Hz and immediately preceding frequent
      standard tones of 1000 Hz were compared between trials containing and trials not
      containing a K-complex (KC trials, NO KC trials, respectively) to the deviant
      tones. The N350 wave to the deviant tones was markedly larger during the KC than
      during the NO KC trials. Also the P210 wave to the 2000 Hz deviant tone showed
      the same phenomenon. No definite evidence was found for the mismatch negativity
      like deflection during the KC trials. ERPs to the standard tones presented
      immediately (625 ms) prior to the deviant tones showed a larger early positive
      wave during the KC trials than during the NO KC trials. No corresponding
      phenomenon could be observed for the identical standard tone presented 1250 ms
      prior to the deviant tones. In all, the results suggest that the sleeping brain
      is momentarily more responsive to incoming sensory events preceding a K-complex
      than preceding a no K-complex response to a stimulus.

PMID- 9146500
TI  - Event-related desynchronization (ERD) in the alpha frequency during development
      of implicit and explicit learning.
AB  - To understand the role of the motor cortex in implicit and explicit learning, we
      studied alpha event-related desynchronization (ERD) while 13 right-handed
      individuals performed a variation of the serial reaction time task (SRTT). EEG
      signals were recorded simultaneously from 29 scalp locations and the ERD was
      computed. During data collection, all subjects developed implicit knowledge,
      demonstrated by shortening of the response time, and explicit knowledge of the
      test sequence. The average ERD maps of all 13 subjects demonstrated that during
      the initial learning, there was a decline in alpha band power that was maximal
      over the contralateral central region. The ERD reached a transient peak amplitude
      at a point when the subjects attained full explicit knowledge, and diminished
      subsequently. The transient peak in ERD was highly significant at C3. These
      electrophysiologic findings support previous studies which have demonstrated that
      motor activity changes as behavior changes over the course of learning.

PMID- 9146501
TI  - Good vs. bad managed care.

PMID- 9146503
TI  - Half empty or half full, it will be a smaller glass.

PMID- 9146502
TI  - Medicare reform should be more than federal budget reform--and it should be done
      soon.

PMID- 9146504
TI  - Trends toward a national health care marketplace.
AB  - In recent years, the health care industry has experienced considerable growth in
      organizations that are national in focus-organizations that operate in multiple
      markets not all clustered in one geographic region. This study summarizes
      information on trends in ownership of various types of health care organizations
      (i.e., HMOs, PPOs, hospitals, physician practices) for purposes of assessing the
      growth rate of national companies and the overall significance of this
      phenomenon. This is followed by a synthesis of factors that encourage or impede
      the growth of national managed care companies, the sector that has exhibited the
      most pronounced growth of national companies. We discuss likely future directions
      and the degree to which national companies may enjoy long-term competitive
      advantages.

PMID- 9146505
TI  - The role of managed care "products" in managed care "plans".
AB  - This paper presents information about the form and structure of managed care
      products offered by group/staff health maintenance organizations (HMOs),
      network/independent practice association (IPA) HMOs, and preferred provider
      organizations (PPOs). The information comes from a 1994 national survey of
      managed care plans and their arrangements with physicians. The findings confirm
      that multiple product offerings are now common in managed care plans. The two
      reasons plans most often cite for including these expanded offerings are to
      respond to customer interest and to ease the transition to more traditional
      managed care. Though plans commonly use a consistent provider network for
      different products, they also vary some arrangements with physicians across their
      products and pay them in different ways. We discuss the implications of our
      findings-the most comprehensive study of these issues to date-to aid in
      understanding the evolution of markets and of managed care, and as a basis for
      the design of future research and the databases it will require.

PMID- 9146506
TI  - Mental health care use, morbidity, and socioeconomic status in the United States
      and Ontario.
AB  - This study focuses on mental health problems and compares the association of
      demographic and socioeconomic factors to the use of mental health specialty care
      and general medical care in the United States and the Canadian province, Ontario.
      It also examines how lack of insurance coverage in the United States and
      perceived need for care affects differences between the two countries. We employ
      a cross-sectional study design using the 1990 U.S. National Comorbidity Survey
      and the 1990 Mental Health Supplement to the Ontario Health Survey. Overall, 8.8%
      of Americans report one or more visits to the health sector for a mental health
      problem, compared to 6.9% of Canadians in Ontario. Americans with the highest
      incomes and no mental morbidity are much more likely to receive services than
      their Canadian counterparts. By contrast, Americans with the lowest incomes and
      high morbidity are much less likely to receive services for mental health
      problems than a similar group of Canadians. These results suggest that universal
      and comprehensive coverage, as exists in Ontario, does not necessarily lead to
      increased use of services with low value. However, the greater prevalence of
      perceived need for care among Americans with higher socioeconomic status and low
      mental morbidity suggests that the United States should be cautious in drawing
      lessons from other countries.

PMID- 9146507
TI  - The changing face of long-term care insurance in 1994: profiles and innovations
      in a dynamic market.
AB  - This study examines buyers and nonbuyers of long-term care insurance. The
      findings show that consumers purchased more comprehensive products in 1994-95
      than they did in 1990, and that they appeared to get better value for the premium
      dollar. While annual sales are increasing at a rate of 25%, the market for long
      term care insurance remains small, and many of the market barriers that existed
      four to five years ago persist today. These include confusion about public
      coverage, concerns about the adequacy of products and how to choose them, policy
      cost, and inadequate information about potential risk for needing long-term care.
      As states target limited public funds toward the indigent, older middle-class
      people will have to deal with exposure to risk for long-term care, and insurance
      may be one way to minimize this exposure.

PMID- 9146508
TI  - The malpractice premium costs of obstetrics.
AB  - This study examined, in 1992, the variation in the level of malpractice premiums,
      and the incremental malpractice premium costs associated with the practice of
      obstetrics for family practitioners and obstetricians. On average, in 1992
      obstetricians and family practitioners providing obstetric services paid
      malpractice premiums of roughly $44,000 and $16,000, respectively. The
      incremental increase in malpractice premium costs represented roughly 70% of the
      premium the physicians would have paid had they not provided obstetric services.
      These results suggest that for both family practitioners and obstetricians, there
      is a considerable premium penalty associated with providing obstetric services
      which may have implications for women's access to obstetric services. Moreover,
      the results make it clear that physicians practicing in different states, and
      different specialists within a state, may face very different malpractice premium
      costs.

PMID- 9146509
TI  - Changes in the 1995 Current Population Survey and estimates of health insurance
      coverage.
AB  - This analysis compares the March 1994 and March 1995 Current Population Survey
      (CPS) counts of the numbers of people with different types of health insurance
      and without any health insurance coverage. The findings contain some surprises:
      there were no changes in the numbers of nonelderly people with Medicaid coverage
      and without any health insurance, and there were increases in the numbers of
      nonelderly people with employer-sponsored health insurance and with
      CHAMPUS/VA/military health care. Four changes were introduced in the CPS in 1995
      and were likely, by themselves, to both raise and lower the estimates of the
      numbers of people with specific types of health insurance coverage. Three of the
      changes relate to questions about health insurance coverage; they coincide with
      the traditional mid-decade shift in the sample framework for the CPS.

PMID- 9146510
TI  - "Best hospitals": a description of the methodology for the Index of Hospital
      Quality.
AB  - Starting in 1991, U.S. News & World Report has published an annual cover story.
      "America's Best Hospitals," for which the National Opinion Research Center (NORC)
      has provided the underlying data. Since 1993, the rankings have been based on a
      combination of data, including physicians' nominations, the American Hospital
      Association's Annual Survey of Hospitals database, and mortality data from the
      Health Care Financing Administration. This article reports on the theoretical
      framework and methodological design of the "Index of Hospital Quality" used in
      the U.S. News & World Report rankings.

PMID- 9146511
TI  - When perception isn't reality.

PMID- 9146512
TI  - Advantages and limitations of the fibula free flap in mandibular reconstruction.
AB  - PURPOSE: The authors analyze the advantages and disadvantages of mandibular
      reconstruction with a fibula free flap in a retrospective study of 29 cases, and
      make comparisons with the iliac free flap and the lateral brachial free flap.
      MATERIAL AND METHODS: Twenty-nine patients (22 male, 7 female) aged 5 to 70 years
      were studied. Functional and esthetic evaluations were performed together with
      radiologic examination of the bony calluses. RESULTS: The fibula free flap has
      advantages for mandibular reconstruction, such as the length of bone available,
      low morbidity of the donor site, and the possibility of using a skin paddle.
      However, there is the disadvantage of not being able to reconstruct large soft
      tissue defects. In addition, bone vascularization is reduced when a large number
      of osteotomies are required. CONCLUSION: This reconstruction technique is
      satisfactory for mandibular defects measuring over 20 cm.

PMID- 9146513
TI  - Radiographic manifestations of multiple myeloma in the mandible: a retrospective
      study of 77 patients.
AB  - PURPOSE: This retrospective study was done to determine the frequency and
      radiographic pattern multiple myeloma in the mandible. PATIENTS AND METHODS:
      Seventy-seven patients with multiple myeloma were studied using skull and
      panoramic radiographs of the jaws made at the time of initial diagnosis. RESULTS:
      Skull manifestations were present in 46.7% and jaw manifestations in 15.6% of the
      cases studied. The pattern of jaw involvement was characterized by osteolytic
      lesions without other radiographic manifestations of bone involvement. There was
      no relationship between the pattern of jaw and extragnathic involvement and
      increased M-component of secreted immune globulin. Jaw involvement was largely
      unaccompained by oral symptoms. CONCLUSION: The results suggest that mandibular
      lesions are a common finding in multiple myeloma.

PMID- 9146514
TI  - Virtual reality for orthognathic surgery: the augmented reality environment
      concept.
AB  - PURPOSE: The objective of this study was to apply virtual reality technology to
      osteotomies of the facial skeleton. MATERIALS AND METHODS: Augmented reality can
      be considered a hybrid of virtual and real environment spaces, which are
      coregistered and simultaneously visualized. Using a see-through HMD (head-mounted
      display) and Interventional Video Tomography intraoperatively, partial visual
      immersion into a patient-related virtual data space augments the surgeon's
      perception as shown in an experimental study and clinical applications. RESULTS:
      Without limiting the surgical judgment, offering continuous observation of the
      operating field, the presented technology additionally provides visual access to
      invisible data of anatomy, physiology, and function and thus guarantees
      unencumbered and fluent surgery. CONCLUSION: Despite current shortcomings,
      augmented reality technology proved to be particularly well suited for use in
      osteotomies of the facial skeleton.

PMID- 9146515
TI  - Stability after surgical correction of mandibular prognathism using the sagittal
      split ramus osteotomy and fixation with poly-L-lactic acid (PLLA) screws.
AB  - PURPOSE: This study was designed to examine skeletal stability after surgical
      correction of mandibular prognathism using a sagittal split ramus osteotomy
      (SSRO) and fixation with poly-L-lactic acid (PLLA) screws. PATIENTS AND METHODS:
      Twenty patients with Class III malocclusion were treated with bilateral SSRO and
      mandibular setback. Ten underwent fixation with titanium screws (group I) and the
      other 10 with PLLA screws (group II). Cephalograms were obtained 2 or 3 days
      postoperatively, and at 3, 6, and 12 months after the operation. Changes in the
      position of upper incisors (U-1), lower incisors (L-1), B-point, and pogonion
      were examined on lateral cephalograms. RESULTS: Certain tendencies for overjet
      and overbite were noted to have decreased more markedly, and changes in the
      position of the skeletal points were greater in group II than in group I.
      However, statistical analysis showed no significant differences between the two
      groups. CONCLUSION: Our results suggest that fixation of the bony segments with
      PLLA screws after SSRO may be used effectively in properly selected cases.

PMID- 9146517
TI  - A study of primary closure of human bite injuries to the face.
AB  - PURPOSE: This study evaluated the management of human bite injuries to the face
      during the period from May 1995 to April 1996. PATIENTS AND METHODS: Data on 30
      patients presenting with human bite injuries during this period were collected on
      specially designed forms. The information was pooled and analyzed. A standardized
      surgical treatment consisting of thorough debridement of the wound followed by
      primary closure either by direct suturing, a local flap, or skin grafting on the
      day of presentation was used. Most of the cases were treated under local
      anesthesia. Patients were prescribed tetanus prophylaxis and a course of
      antibiotics for 1 week. Suture removal was done 1 week postoperatively except for
      the skin grafts, which were uncovered at 10 days postoperation. RESULTS: There
      were 21 males and 9 females ranging in age between 17 and 55 years, with a mean
      age of 31.8 years. Sixty-six percent of the bites involved the lips. The duration
      of injury before presentation ranged from 1 to 4 days. In 27 of the cases (90%),
      wound healing was complete at the time of suture removal. CONCLUSION: The results
      indicate that immediate closure of human bite injuries is safe, even with old
      injuries.

PMID- 9146516
TI  - A comparison of segmental and marginal bony resection for oral squamous cell
      carcinoma involving the mandible.
AB  - PURPOSE: This study reviews the accuracy of preopertive diagnosis of mandibular
      invasion by oral squamous cell carcinoma and assesses the role of marginal
      resection of the mandible in its treatment. PATIENTS AND METHODS: A retrospective
      study of a 5-year cohort of 46 patients who underwent mandibular resection for
      previously untreated oral squamous cell carcinoma was done. Data evaluated
      included age; sex; site and stage of cancer; preoperative clinical, panoramic,
      and computed tomography (CT) evaluations; and histologic findings on the
      resection specimen. The type of mandibular resection (segmental vs marginal) and
      treatment outcome also were compared. RESULTS: Clinical examination, panoramic
      radiographs, and CT scans were 78.5% to 82.6% accurate in diagnosing mandibular
      invasion by squamous carcinoma. Clinical examination and panoramic radiographs
      are more sensitive than CT scans (86.6% vs 53%), but CT scans were more specific
      (92.5% vs 80%). The mandible was involved in 65% of patients with segmental
      resection and 7.6% of patients who had a marginal resection. Nineteen percent of
      the patients in the marginal resection group died of their oral cancer, two of
      five patients with local recurrence. Ten percent of patients in the segmental
      resection group died of oral cancer; no local recurrences were seen. CONCLUSION:
      There is no completely accurate method of diagnosing bony invasion of the
      mandible by oral squamous cell carcinoma. A combination of clinical examination,
      plain radiographs, and computed tomography (CT) scans may improve the diagnosis.
      Marginal resection is best reserved for cancers close to the bone with no
      invasion, minimal cortical invasion, or with early "arrosive" invasion. It is
      best in the symphysis region. Careful case selection will allow a favorable
      oncologic outcome with preservation of the mandibular contour.

PMID- 9146518
TI  - The pullout force for Mitek mini and micro suture anchor systems in human
      mandibular condyles.
AB  - PURPOSE: This study examines the pullout forces and the modes of pullout for the
      Mitek mini and micro suture anchor systems (Mitek Inc., Norwood, MA) when
      inserted into the posterior aspect of the condyle. MATERIAL AND METHODS: Twenty
      mandibular condyles were obtained from embalmed human cadavers. A mini anchor and
      a smaller micro anchor were threaded with braided size 0 and 3-0 polyester
      suture, respectively, and placed in the posterior aspect of each condyle. Pullout
      testing was performed using an Instron materials testing machine. The force and
      mode of pullout were recorded for each specimen. RESULTS: The findings indicate a
      significantly greater mean pullout force of 16.02 lbs for the larger mini anchor
      system as compared with the 10.57 lbs mean pullout force of the micro anchor
      system. The modes of pullout between these implants were also different. Intact
      mini suture anchor systems pulled through the cortical bone in 90% of the trials,
      and suture breakage occurred in 10%. The micro anchors were irreversibly deformed
      on pullout in 65% of the trials, whereas the suture broke in 25% of the trials,
      and the intact suture anchor system pulled through the cortical bone in 10%.
      CONCLUSIONS: The Mitek mini anchor system has a significantly greater pullout
      force from the mandibular condyle than the micro anchor system.

PMID- 9146519
TI  - An in vitro comparison of the mechanical characteristics of three sagittal ramus
      osteotomy fixation techniques.
AB  - PURPOSE: The purpose of this in vitro investigation was to compare the mechanical
      characteristics of three techniques for the rigid internal fixation of simulated
      sagittal ramus osteotomies in terms of their ability to resist vertical loads
      resembling masticatory forces. MATERIALS AND METHODS: Fifteen bovine ribs of
      similar size and shape were subjected to uniform osteotomies resembling a
      sagittal ramus osteotomy. They were divided into three groups and fixed with
      three 2.0-mm bicortical positional screws in an inverted L-pattern, eight
      monocortical screws and a sagittal strut plate, or a hybrid system using three
      2.0-mm bicortical positional screws, five 2.0-mm monocortical screws, and a
      sagittal strut plate. The repaired ribs were secured in a jig, subjected to
      vertically deforming forces, and evaluated for yield load, yield point, maximum
      load, displacement at maximum load, load at 3.0 mm displacement, and stiffness.
      The various groups were compared statistically with a Scheffe multiple comparison
      test. RESULTS: No statistically significant differences existed between the
      positional screw group and the hybrid group (P > .05). No statistically
      significant differences were noted in yield displacement, yield load,
      displacement at maximum load, for any of the groups (P > .05). There were
      differences noted between the monocortical strut group and other groups in
      maximum load, load at 3.0 mm displacement, and stiffness (P > .05). CONCLUSIONS:
      The monocortically fixed sagittal strut plate offers less resistance to maximum
      load and loads at 3.0 mm displacement and is less stiff than either a three
      positional screw system or a hybrid system. No differences existed between the
      three positional screw systems and the hybrid system. However, given the low
      yield loads and yield displacements, these differences may not be clinically
      important.

PMID- 9146520
TI  - Rigid fixation and strain patterns in the pig zygomatic arch and suture.
AB  - PURPOSE: In orthognathic surgery, rigid fixation is routinely used to hold
      together bone fragments that may experience heavy force from attached masticatory
      muscles. Internal fixation plates are assumed to hold bony parts rigidly, but the
      mobility at such sites subjected to normal masticatory function has not been
      measured. The purpose of this study was to investigate in vivo the degree to
      which a linear plate immobilizes separated bones, specifically sutures. MATERIALS
      AND METHODS: Three female miniature pigs (Sus scrofa) had 1.3-mm Synthes titanium
      plates placed across the suture in the zygomatic arch. Foil strain gauges were
      used to record load deformation in the zygomatic and squamosal (temporal) bones
      and across the vertical and horizontal parts of the suture. Strain was recorded
      in vivo during mastication and in anesthetized pigs with electrical stimulation
      of masticatory muscles. RESULTS: Strain at the suture was not reduced from normal
      levels. The plate induced increases in strain within the bones, but the changes
      were slight. CONCLUSION: The results indicate that linear "rigid fixation" does
      not immobilize sutures.

PMID- 9146521
TI  - Spontaneous oroantral fistula.

PMID- 9146522
TI  - A large vascular malformation of the tongue treated with radiation therapy.

PMID- 9146523
TI  - Parotid presentation of Castleman's disease: report of a case.

PMID- 9146524
TI  - Rieger syndrome: a case report.

PMID- 9146525
TI  - Necrotizing fasciitis of the periorbita and forehead.

PMID- 9146526
TI  - Intentional partial odontectomy: review of cases.

PMID- 9146527
TI  - Transient temporal nerve paresis after intraoral subcondylar ramus osteotomy.

PMID- 9146528
TI  - Human papillomavirus-associated tumors of the skin and mucosa.
AB  - This review discusses diseases of the lower genital tract in which the presence
      of human papillomavirus (HPV) DNA is well documented. We discuss epidemiologic,
      clinical, and experimental data supporting a causative role for HPV in mucosal
      malignancies, with emphasis on the role of viral and host factors in their
      pathogenesis. Of special interest is the recently discovered association of
      cutaneous tumors with HPVs, previously known only for tumors in epidermodysplasia
      verruciformis (EV). The frequent detection of EV-specific or EV-related HPVs in
      immunosuppressed persons and in cutaneous tumors in the general population
      supports the importance of EV as a model of cutaneous oncogenesis. We also
      discuss recent serologic findings based on enzyme-linked immunosorbent assay
      results with the use of viruslike particles. This is important both for detection
      of present or past HPV infection and for epidemiologic and immunologic studies.
      Novel therapeutic modalities for HPV tumors and prospects for prophylactic and
      therapeutic vaccination are presented.

PMID- 9146529
TI  - Cutaneous vasculitis in Behcet's disease: a clinical and histopathologic study of
      20 patients.
AB  - BACKGROUND: Despite the frequency of small vessel vasculitis in skin lesions of
      Behcet's disease (BD), BD is classified as a neutrophilic dermatosis. OBJECTIVE:
      Our goal was to determine whether the various cutaneous manifestations of BD are
      secondary to cutaneous vasculitis. METHODS: Twenty-three specimens with
      histologically proven necrotizing vasculitis from 20 of 42 patients with BD were
      investigated. RESULTS: The cutaneous vasculitic manifestations were characterized
      as erythema nodosum-like eruptions, palpable purpura, hemorrhagic blisters,
      infiltrated erythema, Sweet's syndrome-like eruptions, papulopustular lesions,
      and extragenital ulcerations. Combinations of various skin lesions were commonly
      seen in the same patient. Venous vessels in the entire dermis to the subcutis
      were affected with sparing of arterial vessels from middermis to subcutis.
      Histologic features included leukocytoclastic vasculitis in seven and lymphocytic
      vasculitis in 13 patients with extensive to focal localized fibrinoid necrosis of
      vessel walls. CONCLUSION: Cutaneous vasculitis in BD is predominantly venulitis
      or phlebitis. Approximately half (48%; 20 of 42) of BD patients with cutaneous
      lesions had either lymphocytic (31%; 13 of 42) or leukocytoclastic vasculitis
      (17%; 7 of 42). We suggest that BD be considered as a vasculitis-associated
      disease separate from the neutrophilic dermatoses.

PMID- 9146530
TI  - Cutaneous Crohn's disease in children.
AB  - BACKGROUND: Although cutaneous Crohn's disease is well recognized in adults, in
      children it is extremely rare. OBJECTIVE: Our purpose was to describe five
      children with cutaneous Crohn's disease and to review the literature. METHODS:
      The medical records of five children with cutaneous Crohn's disease were
      retrospectively reviewed for clinical features and laboratory data. An extensive
      review of the literature was conducted. RESULTS: Five children, one boy and four
      girls, 6 to 12 years of age at onset, had cutaneous manifestations of Crohn's
      disease. Three had genital swelling, and the other 2 had buttock abscesses. Most
      were seen before the diagnosis of gastrointestinal Crohn's disease was made.
      There have been 80 cases of cutaneous Crohn's disease described, including our
      series. Only 14 were in children. Two thirds of children with cutaneous Crohn's
      disease had genital involvement compared with about half of the adult cases.
      Sixteen of the 80 patients had cutaneous lesions without preceding
      gastrointestinal Crohn's disease. Of these, approximately 70% had genital
      lesions. CONCLUSION: Although Crohn's disease is common in children, cutaneous
      manifestations are rarely a presenting sign. However, when cutaneous Crohn's
      disease is present in children, it commonly precedes the gastrointestinal
      disease.

PMID- 9146531
TI  - Oral contraceptive failure rates and oral antibiotics.
AB  - BACKGROUND: Despite anecdotal evidence of a possibility of decreased
      effectiveness of oral contraceptives (OCs) with some antibiotics, it is not known
      whether antibiotic use in dermatologic practices engenders any increased risk of
      accidental pregnancy. OBJECTIVE: Our purpose was to examine the effect of
      commonly prescribed oral antibiotics (tetracyclines, penicillins, cephalosporins)
      on the failure rate of OCs. METHODS: The records from three dermatology practices
      were reviewed, and 356 patients with a history of combined oral antibiotic/OC use
      were surveyed retrospectively. Of these patients, 263 also provided "control"
      data (during the times they used OCs alone). An additional 162 patients provided
      control data only. RESULTS: Five pregnancies occurred in 311 woman-years of
      combined antibiotic/OC exposure (1.6% per year failure rate) compared with 12
      pregnancies in 1245 woman-years of exposure (0.96% per year) for the 425 control
      patients. This difference was not significant (p = 0.4), and the 95% confidence
      interval on the difference (-0.81, 2.1) ruled out a substantial difference (>
      2.1% per year). There was also no significant difference between OC failure rates
      for the women who provided data under both conditions, nor between the two
      control groups. All our data groups had failure rates below the 3% or higher per
      year, which are typically found in the United States. CONCLUSION: The difference
      in failure rates of OCs when taken concurrently with antibiotics commonly used in
      dermatology versus OC use alone suggests that these antibiotics do not increase
      the risk of pregnancy. Physicians and patients need to recognize that the
      expected OC failure rate, regardless of antibiotic use, is at least 1% per year
      and it is not yet possible to predict in whom OCs may fail.

PMID- 9146532
TI  - Laboratory tests and imaging studies in patients with cutaneous malignant
      melanomas: a survey of experienced physicians.
AB  - BACKGROUND: The presence or absence of metastases is important in determining
      prognosis and treatment options for patients with malignant melanoma (MM).
      Laboratory tests and imaging studies are ordered for patients with MMs but
      without symptoms in an effort to detect occult metastases. However, which
      laboratory tests and imaging studies to order and how often to reorder them is
      not well established. OBJECTIVE: Our purpose was to determine which tests and
      studies are ordered by physicians with major responsibilities for the care of
      patients with MM. METHODS: Physicians were surveyed by questionnaire about the
      laboratory tests and imaging studies they ordered for MM stages 0, I, II, and
      III. RESULTS: Of the 35 physicians queried, 30 (86%) responded to the survey. The
      majority of physicians order tests as follows: no tests for MM in situ;
      roentgenography of the chest with or without initial lactic acid
      dehydrogenase/liver function tests for stages I, II, and III and during follow-up
      for stages IB, II, and III (more frequently as the Breslow thickness increases);
      and baseline computed tomographic or magnetic resonance imaging scans of the
      chest, abdomen/pelvis, and brain for stage III. CONCLUSION: Although the pattern
      of ordering examinations was similar for the majority of respondents, there was
      significant variability among experienced physicians in ordering laboratory tests
      and imaging studies in the search for occult metastases in patients with
      asymptomatic MM. The laboratory tests and imaging studies ordered and their
      frequency depend on the stage of the MM and sometimes on other risk factors.

PMID- 9146533
TI  - Who removes pigmented skin lesions?
AB  - BACKGROUND: Increasing numbers of pigmented skin lesions are being removed
      because of concern about possible malignancy. OBJECTIVE: Our purpose was to
      determine the ratio of benign to malignant pigmented tumors removed by different
      categories of physician and to verify whether any improvement had occurred after
      5 years of educational programs. METHODS: All pigmented lesions submitted to a
      major histopathology service in the years 1989 and 1994 were assessed as to the
      category of physician who removed the lesion, tumor type, and age and sex of the
      patient. RESULTS: Dermatologists had the lowest benign/malignant ratio and
      general practitioners had the highest. General practitioners appeared to have
      difficulty differentiating both seborrheic keratoses and melanocytic nevi from
      malignant lesions; the frequency of these benign lesions was highly dependent on
      the age of the patient. During the 5-year period we observed an improvement among
      general practitioners in the benign/malignant ratio for melanocytic nevi, but not
      for seborrheic keratoses. CONCLUSION: There is room for improvement by physicians
      in differentiating both melanocytic nevi and seborrheic keratoses from melanomas.
      This is especially true for general practitioners, from whom the public in
      Australia and in other countries is encouraged to first seek advice about a
      suspect pigmented lesion.

PMID- 9146534
TI  - Merkel cell carcinoma: report of ten cases with emphasis on clinical course,
      treatment, and in vitro drug sensitivity.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is an uncommon primary neuroendocrine
      skin tumor most often seen in the elderly. The clinical course varies. Treatment
      is controversial and few data on drug sensitivity are available. OBJECTIVE: We
      evaluated the clinical course and treatment of 10 MCC patients and determined MCC
      chemosensitivity. METHODS: Clinical records as well as laboratory and
      histopathologic data from 10 patients with MCC treated in our department were
      examined. Chemosensitivity to various chemotherapeutic agents and interferons of
      MCC cells from four patients was determined in a soft agar clonogenic assay.
      RESULTS: MCC behaved as an aggressive tumor with early and frequent local
      relapses (4 of 10 patients at a 2.2-month average), regional (4 of 10 patients at
      2.5 months), and distant metastases (5 of 10 patients 9.6 months after excision
      of the primary tumor). In all but one patient, regional metastases preceded
      distant ones. Metastatic spread was associated with an average survival of 21
      months from the initial diagnosis. Long-term survival (53+ and 65+ months) was
      observed in two women. Wide excision of the primary tumor, alone or combined with
      adjuvant chemotherapy and radiotherapy, was the most effective treatment. In
      advanced disease, chemotherapy and radiotherapy were not able to induce long-term
      remission. In vitro assays for MCC drug sensitivity revealed cisplatin,
      doxorubicin, and vindesine to be the most active. CONCLUSION: MCC has a poor
      prognosis in advanced stages; therefore the primary tumor should be aggressively
      treated. The in vitro clonogenic assay may help to identify the chemosensitivity
      profile of MCC and to optimize chemotherapy protocols.

PMID- 9146535
TI  - Treatment of chronic palmoplantar eczema with local bath-PUVA therapy.
AB  - BACKGROUND: Systemic PUVA therapy may be useful in the treatment of chronic
      palmoplantar eczema. Topical PUVA-paint avoids some of the unwanted side effects
      of systemic psoralens and has been used successfully in the treatment of
      palmoplantar eczema and psoriasis. However, few data are available on the
      effectiveness of local bath-PUVA therapy in palmoplantar eczema. OBJECTIVE: Our
      purpose was to assess the effectiveness of local bath-PUVA therapy in 28 patients
      with chronic palmar or plantar eczema or both who were resistant to conventional
      topical treatment. METHODS: After fungal or bacterial infection had been excluded
      in all patients, hands or feet or both were soaked for 15 minutes in warm water
      containing 1 mg/L 8-methoxypsoralen. Immediately after, the skin was irradiated
      with increasing doses of UVA, starting with 0.5 J/cm2. PUVA-bath therapy was
      performed 4 times a week up to a total of 25 treatments. No additional therapy
      was allowed except emollients. RESULTS: Excellent or good effects were achieved
      in 93% of the patients with dyshidrotic and in 86% of the patients with
      hyperkeratotic eczema. In the patients with dyshidrotic eczema, the cumulative
      doses and the highest single doses of UVA were lower than those in the patients
      with hyperkeratotic eczema (21.4 vs 27.9 J/cm2 and 2.4 vs 3.0 J/cm2 of UVA), but
      this was not statistically significant. No phototoxic reactions were observed.
      CONCLUSION: Local bath-PUVA therapy is of value in the management of chronic
      palmoplantar eczema resistant to standard modes of topical treatment. Compared
      with topical PUVA-paint, local bath-PUVA therapy has several advantages,
      particularly the absence of phototoxic reactions, severe hyperpigmentation, and
      protracted photosensitivity.

PMID- 9146536
TI  - Treatment of small nevomelanocytic nevi with a Q-switched ruby laser.
AB  - BACKGROUND: Small nevomelanocytic nevi are common and some are of cosmetic
      concern. Conventional therapy may cause a scar or permanent hypopigmentation.
      OBJECTIVE: Our purpose was to determine whether selective photothermolysis of
      pigmented cells by Q-switched ruby laser treatment removes small nevomelanocytic
      nevi in a nonscarring fashion. METHODS: Twelve patients with 18 small
      nevomelanocytic nevi were treated with a Q-switched ruby laser (694 nm, 28 nsec)
      at fluences of 8 J/cm2. Biopsy specimens were obtained after treatment at varying
      time intervals. RESULTS: Twelve lesions (67%) showed a complete response and six
      lesions (33%) had a partial response. The only adverse sequela observed was mild
      fibrosis of the papillary dermis, without loss of papillary architecture.
      CONCLUSION: The Q-switched ruby laser is effective in removing small melanocytic
      nevi. However, some might recur depending on the depth of the nevomelanocytic
      nests.

PMID- 9146537
TI  - Long-term follow-up of cryosurgery of basal cell carcinoma of the eyelid.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common malignant tumor of the
      eyelid and its incidence is increasing. It remains to be established which is the
      best treatment in terms of safety and cost-effectiveness. OBJECTIVE: Our purpose
      was to analyze the long-term treatment results and possible side effects of
      cryosurgery of eyelid BCC. METHODS: During the last 14 years 219 patients (222
      tumors) treated for eyelid BCC with cryosurgery were followed up prospectively
      for up to 10 years. RESULTS: The tumors cleared completely after treatment in all
      patients with no recurrence observed to date. Ninety-two patients were followed
      up for 5 years or more. Complications were few and minor. In 26 treated eyelids
      conjunctival overgrowth was noted. CONCLUSIONS: We conclude that cryosurgery of
      BCC of the eyelid has a high cure rate, is cost-effective, and is well tolerated.

PMID- 9146538
TI  - Adjuvant therapy for cutaneous malignant melanoma.
AB  - We discuss the current status of adjuvant therapy for melanoma by first reviewing
      the rationale and goals of adjuvant therapy and then analyzing the results of
      published randomized trials. We pay particular attention to adjuvant interferon
      trials that raise many challenging issues in the management of patients with
      melanoma at high risk of recurrence. Past adjuvant trials have used
      immunotherapeutic approaches, chemotherapy, radiation therapy, as well as
      hormonal and retinoid therapy. We also summarize ongoing adjuvant trials.

PMID- 9146539
TI  - Is it lymphoma or lymphomatoid papulosis?
AB  - Distinguishing malignancy from premalignant conditions can be difficult.
      Controversy surrounds both the clinical and histologic criteria used to
      distinguish lymphomatoid papulosis, a benign disorder, from CD30+ anaplastic
      large-cell lymphoma. Three case histories illustrate important points in
      categorizing different lymphoproliferative disorders as benign or malignant. We
      emphasize a multidisciplinary approach to improve diagnosis and patient
      management.

PMID- 9146540
TI  - Surgical pearl: the hybrid mattress suture.

PMID- 9146541
TI  - Acquired reactive perforating collagenosis: unilateral umbilicated papules along
      the lesions of herpes zoster.

PMID- 9146542
TI  - Anetoderma after hepatitis B immunization in two siblings.

PMID- 9146543
TI  - Solitary painful piezogenic pedal papule.

PMID- 9146544
TI  - Fixed drug eruptions with feprazone are linked to HLA-B22.

PMID- 9146545
TI  - Conjunctival dermoid cyst in an infant.

PMID- 9146546
TI  - Generalized eruptive keratoacanthoma of Grzybowski: response to cyclophosphamide.

PMID- 9146547
TI  - Extracorporeal photopheresis in the treatment of acute graft-versus-host disease.

PMID- 9146548
TI  - Itraconazole for the treatment of tinea pedis: a dosage of 400 mg/day given for 1
      week is similar in efficacy to 100 or 200 mg/day given for 2 to 4 weeks.

PMID- 9146549
TI  - Epidermolysis bullosa acquisita exacerbated by systemic estrogen and progesterone
      treatment and pregnancy.

PMID- 9146550
TI  - Acute generalized exanthematous pustulosis induced by itraconazole.

PMID- 9146551
TI  - Efficacy of cyclosporine on mucocutaneous manifestations of Behcet's disease.

PMID- 9146552
TI  - Executive summary of the national Partners in Prevention Skin Cancer Conference:
      American Academy of Dermatology and Centers for Disease Control and Prevention.

PMID- 9146553
TI  - Treatment of pyoderma gangrenosum.

PMID- 9146554
TI  - Treatment of stable vitiligo with autologous epidermal grafting and PUVA.

PMID- 9146555
TI  - Topical calcipotriene ointment and etretinate: another combination therapy for
      psoriasis vulgaris.

PMID- 9146556
TI  - Methotrexate-induced toxic epidermal necrolysis in a patient with psoriasis.
AB  - We describe a fatal case of low-dose methotrexate (MTX) toxicity in a patient
      with psoriasis, emphasizing the factors that exacerbate MTX toxicity and
      presenting rescue techniques. The patient had a toxic epidermal necrolysis-like
      condition. MTX cutaneous reactions ranging from toxic epidermal necrolysis to
      specific ulcerations have been described. The use of granulocyte colony
      stimulating factor for leukopenia associated with MTX toxicity is discussed.

PMID- 9146557
TI  - Unilateral nevoid telangiectasia: occurrence in two patients with hepatitis C.
AB  - Unilateral nevoid telangiectasia, a rarely reported disorder, has been said to be
      related to increased estrogen receptors in involved skin. The lesions may be
      congenital or acquired. When acquired it arises almost exclusively during periods
      of relatively increased estrogen levels such as during pregnancy or puberty, or
      in association with alcoholic cirrhosis. We describe unilateral nevoid
      telangiectasia in two young men without any evidence of cirrhosis, but with
      serologic evidence of hepatitis C infection. Tissue specimens from these men were
      analyzed for estrogen and progesterone receptors, but there was no difference in
      involved versus uninvolved skin.

PMID- 9146558
TI  - Systematized inflammatory epidermal nevus with symmetrical involvement: an
      unusual case of CHILD syndrome?
AB  - The CHILD syndrome (congenital hemidysplasia with ichthyosiform nevus and limb
      defects) is usually characterized by lateralization of all associated anomalies.
      It has been assumed that the event of X-inactivation coincides and interferes
      with a clone of organizer cells controlling a large developmental field. A 16
      year-old girl with bilateral manifestations of CHILD syndrome is described. The
      inflammatory skin lesions affected the body folds (ptychotropism) in a
      symmetrical distribution, although only the right side of the neck was involved.
      In addition, absence of several facial muscles, vertebral defects, and shortening
      of the leg on the right side were noted, and a ventricular septum defect was
      present. This unusual case may be explained by the assumption that X-inactivation
      did not coincide with the origin of inducer cell clones controlling large
      morphogenetic fields on either side of the body.

PMID- 9146559
TI  - Successful treatment of Schamberg's disease with pentoxifylline.
AB  - Three patients with Schamberg's disease were treated with pentoxifylline, 300 mg
      daily for 8 weeks. A significant response was observed within 2 to 3 weeks. One
      patient had recurrence after discontinuation of this treatment; but promptly
      responded to resumption of therapy. No adverse effects were noted in any
      patients. We investigated the expression pattern of adhesion molecules in
      relation to perivascular accumulation of lymphocytes in specimens obtained before
      and after treatment with pentoxifylline in these patients. Our results suggest
      that pentoxifylline exerts its therapeutic effects on Schamberg's disease at the
      level of T-cell adherence to endothelial cells and keratinocytes.

PMID- 9146560
TI  - Chronic varicella zoster infection mimicking a basal cell carcinoma in an AIDS
      patient.
AB  - Chronic herpesvirus infections are common in patients infected with HIV. Atypical
      skin lesions secondary to long-standing varicella-zoster virus (VZV) infection
      have been reported. We present a case of an AIDS patient with a chronic VZV
      infection that simulated a basal cell carcinoma. Histologic examination and
      immunohistochemistry confirmed the presence of the virus in the follicular
      epithelium. In the immunocompromised patient, biopsies should be performed on all
      suspicious lesions because medically-treatable infections may take on the
      appearance of malignancy.

PMID- 9146561
TI  - Systemic lupus erythematosus presenting with red lunulae.
AB  - Red lunulae have been observed in association with a large spectrum of cutaneous
      and systemic diseases. We describe a 13-year-old girl with painful red lunulae of
      the fingernails who subsequently developed systemic lupus erythematosus. The
      appearance of Beau's lines suggested inflammation of the nail matrix. Oral
      prednisone produced significant improvement in the nail changes. To our
      knowledge, red lunulae have not been previously recognized as the presenting sign
      of systemic lupus erythematosus.

PMID- 9146563
TI  - Lichenoid dermatitis after consumption of gold-containing liquor.
AB  - Medicinal gold has a well-known side effect profile that includes mucocutaneous
      eruptions. We describe three patients with a pruritic dermatitis that began after
      consumption of a gold-containing alcoholic beverage. Blood and urine gold levels,
      chemistry panels, hepatitis screens, skin biopsies, and patch tests were
      performed. The gold-containing liquor was analyzed for the presence and quantity
      of gold. The liquor consumed by all of the patients was a cinnamon schnapps with
      free-floating gold-colored flakes. Gold is present in the liquid portion of this
      liquor and in the solid flakes. Elevated levels of gold in the urine and blood
      were present in one patient 3 months after last drinking this beverage. Another
      patient had a positive patch test to gold sodium thiosulfate. All patients
      experienced improvement of their dermatitis after they stopped drinking the gold
      containing liquor.

PMID- 9146562
TI  - Aleukemic "leukemia cutis" of monocytic lineage.
AB  - We describe aleukemic leukemia cutis (ALC) in a 50-year-old woman who presented
      with numerous skin nodular lesions and lack of peripheral blood and bone marrow
      involvement until late in the evolution of her disease. We emphasize the value of
      immunohistochemical studies to distinguish ALC from cutaneous large cell
      lymphoma.

PMID- 9146564
TI  - Sebaceous adenitis.
AB  - A 32-year-old man had an asymptomatic erythematous, annular and circinate
      eruption on the face for 2 months. Histologic examination revealed sebaceous
      lobules surrounded by a lymphomonocytic infiltrate and some areas of necrotic
      sebocytes. The lesions healed without treatment in 1 month. These clinical
      features can be observed in "neutrophilic sebaceous adenitis," recently described
      by Renfro et al. The most striking abnormality is the nearly exclusive
      perisebaceous distribution of the dermal cellular infiltrate with inflammatory
      cell permeation of the sebaceous epithelium.

PMID- 9146565
TI  - Multiple lesions of sporotrichoid leishmaniasis in a Filipino expatriate.
AB  - Sporotrichoid cutaneous leishmaniasis (CL) was diagnosed in a Filipino man who
      had worked in Saudi Arabia for 2 years. Two primary lesions-one on the forearm
      and one on the abdomen-were characterized by "satellite" papules and subcutaneous
      nodules extending proximally in a sporotrichoid pattern. Leishmania organisms
      were found in both primary lesions and a subcutaneous nodule. There was no
      evidence of systemic involvement. Recognition that Old World CL may disseminate
      through lymphatic channels has diagnostic and therapeutic importance.

PMID- 9146566
TI  - Verrucosis of hands and feet in a patient with combined immune deficiency.
AB  - In immunocompromised patients, warts occur frequently and can be extensive. We
      describe a 24-year-old patient with severe therapy-resistant warts. In addition
      to human papillomavirus infection, he had chronic sinusitis, candidiasis, and
      atopic dermatitis. Anergy to delayed-type hypersensitivity skin test reaction,
      significant CD4 lymphopenia, and diminished in vitro T-cell proliferative
      response and interferon-gamma production indicated a deficiency of cellular
      immunity. Extremely low concentrations of serum IgM and IgG2 and a severe
      deficiency of in vitro IgM production pointed also to a humoral immunodeficiency
      syndrome. This case represents a combination of cellular and humoral
      immunodeficiencies that has not been previously described in association with
      warts.

PMID- 9146567
TI  - Mastication of verruca vulgaris associated with esophageal papilloma: HPV-45
      sequences detected in oral and cutaneous tissues.
AB  - Human papillomaviruses (HPVs) are double-stranded, circular, epitheliotropic DNA
      viruses of which nearly 70 types have been identified. Specific HPV types exhibit
      a predilection to infect certain sites; however, occurrence is not unique or
      restricted to these sites. HPV typing may also be helpful in determining the
      oncogenic potential of HPV lesions. The most common HPV types, 6 and 11, are
      associated with benign mucosal lesions, whereas types 18, 16, 31, and 33 are
      thought to confer a high rate of malignant transformation. We describe a patient
      with both palmar verrucae and esophageal papillomatosis that proved to be HPV
      type 45 by polymerase chain reaction. HPV 45 has a high homology to HPV 18 and is
      a member of the relatively new "high-risk" mucosal HPV family in terms of
      cervical oncogenic potential. To our knowledge, HPV 45 has never been reported in
      cutaneous warts or esophageal lesions.

PMID- 9146568
TI  - Terbinafine therapy may be associated with the development of psoriasis de novo
      or its exacerbation: four case reports and a review of drug-induced psoriasis.
AB  - Adverse effects may occur in 10.4% of patients receiving terbinafine therapy,
      with cutaneous reactions in 2.7%. We describe the development of psoriasis in
      four patients who took oral terbinafine. Two patients had plaque-type psoriasis
      that flared 12 and 17 days, respectively, after starting terbinafine. Another
      patient developed pustular-type psoriasis de novo after 27 days of terbinafine
      therapy. The fourth patient was a psoriatic with stable plaque disease who
      experienced a pustular flare after taking terbinafine for 21 days. We are aware
      of only one report in the literature in which a patient developed pustular
      psoriasis de novo after 5 days of terbinafine therapy. In all patients the
      psoriasis cleared or lessened after discontinuation of terbinafine and
      institution of antipsoriatic therapy.

PMID- 9146569
TI  - Subcutaneous phaeohyphomycosis and nocardiosis in a kidney transplant patient.
AB  - Phaeohyphomycosis and nocardiosis are uncommon infections that are more
      frequently reported in immunocompromised patients. To our knowledge, this is the
      first report of subcutaneous phaeohyphomycosis caused by Exophiala jeanselmei in
      association with systemic infection with Nocardia asteroides. The patient's
      phaeohyphomycosis responded to surgical excision and multi-drug therapy, and the
      patient underwent prolonged therapy with trimethoprim/sulfamethoxazole for
      treatment of the nocardiosis.

PMID- 9146570
TI  - Minocycline-related lupus erythematosus with associated liver disease.
AB  - A young woman developed minocycline-related lupus erythematosus with associated
      autoimmune hepatitis. All clinical and laboratory abnormalities returned to
      normal when the drug was stopped. The symptoms worsened dramatically upon
      rechallenge, strongly suggesting the reaction was related to the minocycline.

PMID- 9146571
TI  - Cutaneous and neurologic disease associated with HTLV-I infection.
AB  - Human T-lymphotropic virus type I (HTLV-I) is the etiologic agent of HTLV-I
      associated myelopathy (HAM)/tropical spastic paresis (TSP), and adult T-cell
      leukemia/lymphoma (ATLL). ATLL has been associated with HTLV-I in the
      southeastern United States. However, to our knowledge, no case reports of HAM/TSP
      in association with ATLL occurring in the United States have been described. We
      describe a 40-year-old black woman with a 10-year history of recalcitrant
      psoriasiform eruption and erythrodermic flares. Medical history is additionally
      significant for a 2-year history of HTLV-I-associated myelopathy and lower
      extremity spastic paresis. Polymerase chain reaction with Southern blot analysis
      was used to detect HTLV-I proviral genome from frozen skin biopsy specimens and
      peripheral blood mononuclear cells.

PMID- 9146572
TI  - Widespread cutaneous necrosis and antiphospholipid antibodies: two episodes
      related to surgical manipulation and urinary tract infection.
AB  - Widespread cutaneous necrosis (WCN) associated with antiphospholipid antibodies
      is rare. Its mechanisms have yet to be elucidated, and there are no well
      established guidelines for its management. We describe a woman who had two
      episodes of WCN related to surgical manipulation for urinary tract obstruction
      and urinary tract infection. Lupus anticoagulant was always positive. In the
      second episode anticardiolipin antibodies were elevated, and protein C levels
      were temporarily decreased. We found only ten previously reported cases of WCN
      associated with antiphospholipid antibodies, none of which were related to
      surgical manipulation.

PMID- 9146573
TI  - Is cutaneous plasmacytosis a distinct clinical entity?
AB  - We describe a Japanese patient with cutaneous plasmacytosis whose clinical course
      we observed for 5 years. We also review 26 patients with this condition,
      including 24 Japanese and two non-Japanese, reported in detail. This review
      revealed that this condition has characteristic clinical and pathologic features
      and should be considered a distinct clinical entity. The reason for the
      predominant occurrence of cutaneous plasmacytosis in Japanese patients is
      unknown.

PMID- 9146574
TI  - Acute radiodermatitis after radiofrequency catheter ablation.
AB  - Radiofrequency (RF) catheter ablation is used in the treatment of a variety of
      arrhythmias. This report describes the development of acute radiodermatitis after
      two prolonged RF catheter ablation procedures for supraventricular tachycardia.
      It also reviews the characteristics and treatment of radiation-induced skin
      reactions.

PMID- 9146575
TI  - Commentary on prostatic neovascularization and vascular endothelial growth
      factor.

PMID- 9146576
TI  - Urological complications of pancreatic transplantation.
AB  - PURPOSE: Pancreas transplantation is increasingly being used in the treatment of
      type I insulin-dependent diabetes mellitus. Because bladder drainage of the
      exocrine pancreatic secretion is the procedure of choice, urological
      complications are frequent. As the number of these procedures increases the
      urologist will have an extended role in the management of the postoperative
      complications, the majority of which are urological. MATERIALS AND METHODS: The
      literature from 1985 on the complications related to pancreas transplants was
      reviewed. RESULTS: Approximately 50 to 60% of bladder drained pancreas transplant
      recipients will have a urological complication postoperatively. CONCLUSIONS: The
      increasing application of bladder drained pancreas transplantation in the
      treatment of type I insulin-dependent diabetes mellitus necessitates that the
      clinical urologist is familiar with the management of complications related to
      this procedure.

PMID- 9146577
TI  - Vaginal mucosal immunization for recurrent urinary tract infection: phase II
      clinical trial.
AB  - PURPOSE: Decreased local immunity to uropathogenic bacteria may be a factor
      predisposing women to recurrent urinary tract infections. Our phase I study
      demonstrated the safety of a multi-strain vaccine administered as a vaginal
      suppository. A phase II study was conducted to determine vaccine efficacy.
      MATERIALS AND METHODS: A total of 91 women susceptible to recurrent urinary tract
      infections was entered into the study and the courses were analyzed in a
      randomized, double-blind, placebo controlled trial of vaginal mucosal
      immunization. Subjects received 3 vaginal suppositories at weekly intervals.
      Depending on the treatment group each suppository contained 1 of 2 vaccine doses
      or suppository material only. Each patient was followed for 5 months to record
      infection episodes, and obtain urine, vaginal irrigates and serum to measure
      immunological responses. RESULTS: Immunogen treated women who were off antibiotic
      prophylaxis throughout the study had a significant delay in interval to
      reinfection during the first 8 weeks compared to women receiving placebo. Mean
      interval until reinfection was delayed from 8.7 weeks for placebo treated to 13
      weeks for vaccine treated women. Immunological responses in serum, urine and
      vaginal fluid were variable. No serious adverse effects were observed.
      CONCLUSIONS: These data demonstrate that vaginal mucosal immunization can enhance
      resistance to urinary tract infections in susceptible patients.

PMID- 9146578
TI  - Clinical value of renovascular resistive index measurement in the diagnosis of
      acute obstructive uropathy.
AB  - PURPOSE: We evaluated the clinical use of the renal resistive index in
      identifying patients with acute urinary tract obstruction. MATERIALS AND METHODS:
      Of 54 patients with suspected acute urinary tract obstruction who underwent
      measurements of renal resistive index 19 had unilateral obstruction documented
      with excretory urography and comprise our study sample. The contralateral
      nonobstructed kidneys served as controls. Criteria for obstruction were a
      resistive index of 0.70 or greater or a side to side difference of 0.10 or
      greater. We calculated sensitivity, specificity, and positive and negative
      predictive values. RESULTS: Sensitivity for obstruction was 42% with 11 false
      positive cases, specificity was 79%, and positive and negative predictive values
      were 67 and 57%, respectively. CONCLUSIONS: Renal resistive index measurements
      are not valuable in detecting acute urinary tract obstruction.

PMID- 9146579
TI  - Nonoperative treatment of major blunt renal lacerations with urinary
      extravasation.
AB  - PURPOSE: We determined whether nonoperative treatment of major renal lacerations
      with urinary extravasation adversely affects patient outcome. MATERIALS AND
      METHODS: We reviewed all nonoperatively treated patients who presented between
      1983 and 1994 with blunt renal trauma with major lacerations on initial staging
      computerized tomography. Patients with major lacerations associated with (31) and
      without (15) extravasation were compared for complications, blood transfusions
      and length of hospital stay. RESULTS: Urinary extravasation spontaneously
      resolved in 27 of 31 patients (87.1%), while 4 (12.9%) required a ureteral stent
      for persistent extravasation. No complications occurred in patients without
      extravasation. Mean hospitalization was 8.3 and 7.7 days for patients with
      isolated renal injuries with and without extravasation, respectively. Blood
      transfusions were required in 4 patients with and none without extravasation.
      CONCLUSIONS: Nonoperative treatment of major renal lacerations with urinary
      extravasation is safe and effective. Although delayed intervention may be
      required, complications can often be treated with endourological or percutaneous
      methods.

PMID- 9146580
TI  - Horseshoe kidney is associated with an increased relative risk of primary renal
      carcinoid tumor.
AB  - PURPOSE: Carcinoid tumor is a rare neoplasm of the kidney with an unknown
      histogenesis. Of only 31 cases previously reported in the literature 4 arose
      within horseshoe kidneys. We report a case of primary carcinoid tumor arising
      within a horseshoe kidney and discuss the unique insight it provided into the
      pathogenesis of this tumor. MATERIALS AND METHODS: We reviewed in detail all 31
      reported cases of renal carcinoid tumor and, using reported incidence rates of
      horseshoe kidney, we calculated the relative risk of renal carcinoid tumor
      arising within a horseshoe kidney. Immunohistochemical staining for
      neuroendocrine related markers was performed on tissue sections from the present
      carcinoid tumor, the adjacent kidney and 5 control samples of normal renal
      parenchyma. RESULTS: Of the reported tumors 15.6% occurred in horseshoe kidneys,
      yielding a calculated relative risk of 62. The present tumor was multifocal,
      arising from the wall of a cystic lesion and possibly representing a dilated
      calix within the isthmus. Intestinal epithelium lining the cyst cavity exhibited
      multifocal neuroendocrine cell hyperplasia with an immunohistochemical profile
      identical to that of the carcinoid tumor cells. CONCLUSIONS: The relative risk of
      renal carcinoid tumor developing in a horseshoe kidney is markedly greater than
      that for Wilms tumor or transitional cell carcinoma. The clinical course of renal
      carcinoid tumor arising within a horseshoe kidney appears to be more benign than
      that of the nonhorseshoe variant. Our observations support the hypothesis that
      renal carcinoid tumors may arise from neuroendocrine cells within foci of
      metaplastic or teratomatous epithelium within the kidney.

PMID- 9146581
TI  - Patterns of tumor recurrence and guidelines for followup after nephron sparing
      surgery for sporadic renal cell carcinoma.
AB  - PURPOSE: We delineated patterns of tumor recurrence and developed guidelines for
      followup after nephron sparing surgery for sporadic renal cell carcinoma.
      MATERIALS AND METHODS: Before December 1994, 327 patients underwent nephron
      sparing surgery for sporadic localized renal cell carcinoma at our clinic. Mean
      postoperative followup was 55.6 months. The course and outcome for patients with
      postoperative recurrent renal cell carcinoma were reviewed in detail. RESULTS:
      Renal cell carcinoma recurred after nephron sparing surgery in 38 patients
      (11.6%), including 13 (4.0%) who had local tumor recurrence with (7) or without
      (6) metastatic disease and 25 (7.6%) who had metastatic disease without local
      tumor recurrence. Recurrent renal cell carcinoma was detected by associated
      symptoms in 25 patients and by a followup chest x-ray or abdominal computerized
      tomography (CT) in 13. The respective incidences of postoperative local tumor
      recurrence and metastatic disease according to initial pathological tumor stage
      were 0 and 4.4% for stage T1, 2.0 and 5.3% for stage T2, 8.2 and 11.5% for stage
      T3a, and 10.6 and 14.9% for stage T3b disease. The peak postoperative intervals
      until local tumor recurrence were 6 to 24 months (7 of 10 patients with stage T3
      renal cell carcinoma) and longer than 48 months (all 3 with stage T2 disease).
      Patients with isolated local tumor recurrence had better survival compared to
      those with local tumor recurrence and metastatic disease or metastases only.
      CONCLUSIONS: Followup for recurrent malignancy after nephron sparing surgery for
      renal cell carcinoma can be tailored according to the initial pathological tumor
      stage. All patients should be evaluated yearly with a medical history, physical
      examination and select laboratory studies. Patients with stage T1 renal cell
      carcinoma require no additional monitoring, while those with stage T2 disease
      should also undergo a yearly chest x-ray and abdominal CT every 2 years. The same
      recommendations are offered for patients with stage T3 renal cell carcinoma
      except that abdominal CT should be done every 6 months for the first 2 years
      postoperatively.

PMID- 9146582
TI  - Spiral computerized tomography in the evaluation of acute flank pain: a
      replacement for excretory urography.
AB  - PURPOSE: We determined the value of noncontrast enhanced spiral computerized
      tomography (CT) in the evaluation of suspected renal colic. MATERIALS AND
      METHODS: Thin section (5 mm.) noncontrast enhanced CT was used to evaluate 100
      patients presenting to the emergency room with flank pain. The 55 patients with
      ureteral obstruction were followed at the urology outpatient clinic and by
      telephone interview, while 45 without ureteral obstruction were followed by
      telephone interview and chart review. Sensitivity, specificity, and positive and
      negative predictive values for CT were determined, with passage, retrieval or
      identification of a stone on a retrograde study considered the gold standard for
      diagnosis. RESULTS: A total of 89 patients had adequate clinical followup to
      assess outcome accurately. Of 55 patients with ureteral obstruction on CT 11
      underwent endoscopic stone removal, while 44 were treated conservatively with
      stone passage documented in 39. Of the 45 patients without ureteral stones
      identified 38 did not pass calculi and CT provided a definite diagnosis in 14.
      There was 1 false-negative study. The results yielded 98% sensitivity, 100%
      specificity, and 100% positive and 97% negative predictive values. CONCLUSIONS:
      Noncontrast enhanced spiral CT was accurate and reliable in detecting obstructing
      ureteral calculi in patients with flank pain.

PMID- 9146583
TI  - Flexible ureteroscopy: Washington University experience with the 9.3F and 7.5F
      flexible ureteroscopes.
AB  - PURPOSE: Recent advances in the design of flexible ureteroscopes have resulted in
      smaller caliber instruments. We review our experience with the smaller flexible
      ureteroscopes, and compare the efficacy and efficiency of the newer 7.5F to the
      standard 9.3F flexible instruments. MATERIALS AND METHODS: Between January 1991
      and 1995, 69 male and 41 female patients (mean age 57 years, range 16 to 91)
      underwent 116 retrograde flexible ureteroscopic procedures for a variety of
      diagnostic and therapeutic indications. A 9.3F ureteroscope (group 1) was used in
      71 patients and a 7.5F instrument (group 2) was used in 39. RESULTS: Patients in
      group 2 received sedation analgesia significantly more often than those in group
      1 (56 versus 35%, p = 0.04). Active dilation of the ureteral orifice was required
      less often in group 2 (22.5%) than in group 1 (58%, p < or = 0.05). The total
      success rate for stone management, and diagnosis and/or treatment of an upper
      urinary tract lesion was 98.3 and 100%, respectively, in group 1, and 90 and
      100%, respectively, in group 2 (p = 0.17). Of the 71 patients in group 1, 17
      (24%) were treated on an outpatient basis, compared to 14 of 39 (49%) in group 2
      (p = 0.16). No intraoperative or postoperative major complications were
      encountered in either group. Group 2 required less postoperative analgesia (p =
      0.05). No ureteral stricture occurred in either group at an average followup of
      9.5 months postoperatively (range 2 to 35). CONCLUSIONS: For ureteral and renal
      pathological conditions the 7.5F ureteroscope is as effective as the 9.3F
      instrument diagnostically and therapeutically. The 7.5F ureteroscope usually can
      be used with sedation analgesia. Also, the smaller 7.5F ureteroscope is
      associated with less need for active ureteral dilation, minimal postoperative
      discomfort and a brief hospital stay.

PMID- 9146584
TI  - Ureteroscopic stone removal in the distal ureter. Why change?
AB  - PURPOSE: We compared our experience with ureteroscopic stone basket manipulation
      under fluoroscopic guidance to ultrasound ureterolithotripsy for distal ureteral
      stone removal. MATERIALS AND METHODS: Retrospectively, we analyzed the medical
      records of 981 patients with ureteral calculi between January 1994 and December
      1995, of whom 483 (49%) were treated for stones in the lower ureter and
      constituted our study group. The decision of when to perform lithotripsy (group
      2) versus a basket procedure (group 1) was based on a prospective nonrandomized
      study and both groups were compared historically. All 322 patients in group 1
      (mean age 49 years, range 14 to 86) primarily underwent ureteroscopic stone
      basket manipulation using the 4-wire Segura* basket. If the calculus could not be
      removed with the basket and another procedure was necessary, the case was
      considered a failure. The 161 patients in group 2 (mean age 37 years, range 14 to
      74) underwent initially ultrasound ureterolithotripsy for stone fragmentation
      followed or not by removal of the fragments with the basket. Stone size did not
      differ significantly between groups 1 (mean 0.9 cm., range 0.6 to 1.7) and 2
      (mean 0.8 cm., range 0.7 to 2.0). Ureteroscopy was performed in both groups with
      epidural anesthesia and on an outpatient basis in the majority of cases. RESULTS:
      The stone-free rate after 1 procedure was 98.1 and 95.6% in group 1 and 2,
      respectively. For group 2 versus group 1 the operative time was longer (mean 50,
      range 25 to 90 versus mean 19 minutes, range 11 to 40, respectively, p < 0.001),
      the complication rate was greater (16.1 versus 4.3%, respectively, p < 0.001) and
      average hospital stay was longer (2.1 versus 0.15 day, respectively, p < 0.001).
      CONCLUSIONS: Ureteroscopic stone treatment with basket manipulation under
      fluoroscopic guidance or ultrasound ureterolithotripsy provided a high stone-free
      rate. However, stone removal with the basket manipulation technique should be
      considered the first choice for treatment of small distal ureteral calculi based
      on the minimal morbidity, and short operative and recovery times.

PMID- 9146585
TI  - Ureteroscopy.

PMID- 9146586
TI  - Double folded rectosigmoid bladder with a new ureterocolic antireflux technique.
AB  - PURPOSE: We present a new method of urinary diversion to the rectum. MATERIALS
      AND METHODS: Between 1992 and 1995 a new surgical procedure was used in 32 women,
      20 men and 12 children 3 to 60 years old (mean age plus or minus standard
      deviation 35.4 +/- 2.2). The main indication for diversion was invasive bladder
      carcinoma. Surgery entailed creation of an S-shaped double folded rectosigmoid
      reservoir with implantation of the ureters via an extramural serous lined
      antireflux technique. RESULTS: One patient died of a massive pulmonary embolism
      postoperatively. Followup ranged from 6 to 36 months (mean 19.2 +/- 7.0). During
      the observation period 6 patients died of local recurrence and/or distant
      metastasis within 8 months. Of the patients 57 are currently evaluable. All
      patients are continent during the day with an emptying frequency of 2 to 4 times.
      Nocturnal enuresis was observed in 4 children who responded favorably to
      imipramine hydrochloride therapy. Upper urinary tract function was maintained or
      improved in 95% of the patients. No clinical evidence of acidosis was observed,
      since all patients were kept on prophylactic oral alkalization. CONCLUSIONS: The
      procedure can circumvent some of the inherent disadvantages of
      ureterosigmoidostomy and is a good alternative to orthotopic bladder substitution
      when the urethra cannot be used.

PMID- 9146587
TI  - The efficacy of intravesical Tice strain bacillus Calmette-Guerin in the
      treatment of interstitial cystitis: a double-blind, prospective, placebo
      controlled trial.
AB  - PURPOSE: Interstitial cystitis is a debilitating bladder disease of unknown
      etiology with no cure. A recent report suggested that bacillus Calmette-Guerin
      (BCG) may be effective in the treatment of interstitial cystitis. A randomized,
      prospective, double-blind, placebo controlled trial to evaluate the safety and
      efficacy of intravesical BCG in treating interstitial cystitis was done.
      MATERIALS AND METHODS: Patients meeting the National Institute of Arthritis,
      Diabetes and Digestive and Kidney Diseases criteria for interstitial cystitis
      received 6 weekly instillations of Tice strain BCG or placebo. Periodic
      questionnaires, voiding diaries and cystometrograms were obtained. A total of 30
      evaluable subjects was enrolled in the study with a mean followup of 8 months
      (range 6 to 13). Based on an exit questionnaire a responder was defined as one
      who rated the interstitial cystitis symptoms as moderately improved or better.
      RESULTS: A 60% BCG response rate was noted, compared to a 27% placebo response
      rate. Minimum voided volume and quality of life improved in the BCG group
      compared to placebo. Adverse events were similar in each group, mostly irritative
      in nature, and no significant systemic events were noted. CONCLUSIONS:
      Intravesical Tice strain BCG appears to be safe and efficacious in the treatment
      of interstitial cystitis. Additional studies must be performed to confirm the
      results of this pilot study.

PMID- 9146588
TI  - Anterior flap extraperitoneal cystoplasty.
AB  - PURPOSE: We report on our initial experience with the anterior flap
      extraperitoneal cystoplasty for refractory voiding symptoms secondary to detrusor
      hyperactivity. MATERIALS AND METHODS: A total of 27 patients underwent anterior
      flap extraperitoneal cystoplasty, the principles of which include a Pfannenstiel
      skin incision, a small peritoneotomy with minimal manipulation of the bowel,
      extraperitoneal bowel resection with ileovesical anastomosis and creation of an
      anterior bladder wall flap. RESULTS: Convalescence was uneventful in 25 patients
      (92%). Oral intake resumed on postoperative day 3 or 4, and the patient was
      discharged home on postoperative day 5 or 6. Voiding symptoms resolved or
      improved significantly in 92% of patients, who were dry or used 1 or no pads a
      day. Two complications required prolonged hospitalization. CONCLUSIONS: Anterior
      flap extraperitoneal cystoplasty is a safe and effective treatment that has the
      potential to decrease postoperative complications and recovery time.

PMID- 9146589
TI  - Metabolic alterations at different levels of renal function following continent
      urinary diversion through colonic segments.
AB  - PURPOSE: We evaluated the influence of renal function on electrolyte and acid
      base homeostasis in patients with colonic reservoirs for urine and the ability of
      these patients to handle an acute acid load. MATERIALS AND METHODS: The 19
      patients studied were divided into 2 groups according to preservation of the
      glomerular filtration rate at last followup: group 1-well preserved glomerular
      filtration rate (mean 100 ml. per minute per 1.73 m.2) with an average followup
      of 8.5 years and group 2-slight to moderate decrease in glomerular filtration
      rate (mean 55 ml. per minute per 1.73 m.2) with a mean followup of 10.5 years.
      Renal tubular function was evaluated by urinary levels of protein alpha 1
      microglobulin. Baseline serum and urine samples were analyzed for metabolic
      parameters, and baseline arterial blood gas was measured. Immediately thereafter
      ammonium chloride loading was performed. RESULTS: Some difference in acid-base
      homeostasis was found with slight hyperchloremic metabolic acidosis noted in 4
      patients in group 2. Moreover, calcium homeostasis was influenced, with lower
      levels of ionized calcium noted in group 2. However, no difference was found in
      the ability of the patients in both groups to handle an acute acid challenge.
      CONCLUSIONS: Patients with a glomerular filtration rate of approximately 55 ml.
      per minute per 1.73 m.2 have sufficient renal function to compensate for the
      chronic endogenous acid load noted after urinary diversion and they can also
      handle an acute acid load adequately. Further studies are necessary to evaluate
      the long-term effects of a chronic endogenous acid load, for example on bone
      metabolism, in patients with impaired renal function after urinary intestinal
      diversion.

PMID- 9146590
TI  - No evidence of metabolic disorders 10 to 22 years after Camey type I ileal
      enterocystoplasty.
AB  - PURPOSE: Resection of ileal segments may results in malabsorption and a decrease
      in intestinal uptake of different substances. The use of intestinal segments in
      the urinary tract may also cause metabolic disorders. We studied long-term
      metabolic consequences of enterocystoplasty after radical cystoprostatectomy for
      bladder cancer. MATERIALS AND METHODS: We reviewed 17 patients with a Camey type
      I enterocystoplasty for a mean of 12.9 years (range 10 to 22) after radical
      cystoprostatectomy. The enterocystoplasty was constructed with a 35 cm. ileal
      segment resected 20 cm. proximal to the ileocecal valve. All patients underwent
      complete physical and radiological examinations, including renal ultrasonography
      and excretory urography. Laboratory studies included blood count with mean
      corpuscular volume and packed cell volume. Serum was analyzed for electrolytes,
      hepatic function, cholesterol, triglycerides, albumin, protein, vitamins B12 and
      B9, iron, ferritin, calcium, phosphate, vitamin D, parathyroid hormone, urea,
      creatinine, creatinine clearance and prostate specific antigen. In addition urine
      calcium, protein, creatinine and pH were measured, and a midstream urine specimen
      was obtained. RESULTS: There was no evidence of metabolic acidosis, impairment of
      phosphorus and calcium metabolism, vitamin D deficiency or parathyroid hormone
      disturbance. All other laboratory tests were within the normal range. Mean
      creatinine was 106 mumol./l., mean creatinine clearance was 1.5 ml. per second
      per m.2 and mean prostate specific antigen was 0.2 ng./ml. No patient had post
      void residual urine or a dilated upper urinary tract. CONCLUSIONS: This ileal
      bladder substitute does not induce long-term metabolic anomalies. However, these
      results may be due to the short ileal length used in the Camey type I technique
      and the absence of post-void residual urine obtained by good urinary training
      (that is sustained voiding function).

PMID- 9146591
TI  - Minimizing morbidity from reconstructive bladder surgery.

PMID- 9146592
TI  - Screening cystoscopy and survival of spinal cord injured patients with squamous
      cell cancer of the bladder.
AB  - PURPOSE: Yearly cystoscopy has been advocated in spinal cord injured patients
      with chronic or recurrent urinary tract infections secondary to the increased
      risk of squamous cell cancer of the bladder. We examined the effectiveness of
      this protocol in our patients. MATERIALS AND METHODS: The medical records of all
      spinal cord injured patients with squamous cell cancer of the bladder between
      1980 and 1996 were reviewed for the method of detection of the lesion. Screened
      patients (those presenting with chronic or recurrent urinary infections) were
      considered asymptomatic and were compared to symptomatic patients (those
      presenting with overt signs or symptoms of the bladder lesion) with respect to
      age, latency since spinal cord injury, treatment of neurogenic bladder, therapy,
      pathological stage and survival. RESULTS: Of 14 patients (9 symptomatic at
      presentation) 13 underwent cystoprostatectomy, while 1 presented with metastatic
      disease and was treated with supportive care only. Three symptomatic patients
      received adjuvant radiation therapy for positive lymph nodes or margins.
      Pathological stage was more advanced in the symptomatic group, including 7
      patients (78%) with stage pT3a or pT3b (4 had positive lymph nodes), 1 with stage
      pT1N0M0 and 1 with stage pT2N0M0 cancer. In the asymptomatic group 3 patients had
      stage pT2N0M0, 1 had stage pT3aN0M0 and 1 had pT3bN0M0 disease. Overall and
      cancer specific survival rates for symptomatic patients were 44 and 50%,
      respectively, with a median of 40 months to death. In the asymptomatic group
      there was 1 noncancer related death, while the remaining patients were alive at a
      mean followup of 8.2 years. CONCLUSIONS: Cystoscopy to screen for squamous cell
      cancer of the bladder in spinal cord injured patients with chronic or recurrent
      urinary tract infection results in an earlier stage at diagnosis and appears to
      convey a survival advantage. Such a protocol should be strictly followed and
      careful prospective studies must be performed to ascertain if this will become
      significant.

PMID- 9146593
TI  - The use of urine cytology for diagnosing bladder cancer in spinal cord injured
      patients.
AB  - PURPOSE: The diagnosis of bladder cancer in spinal cord injured patients is
      complicated by inflammatory changes caused by long-term indwelling catheters,
      which make cystoscopic followup difficult. We evaluated cytology as an aid in
      diagnosing bladder cancer in spinal cord injured patients. MATERIALS AND METHODS:
      The charts of 208 spinal cord injured patients were reviewed retrospectively from
      January 1988 to July 1995 to define the value of cytology in the diagnosis of
      bladder cancer in this population. In all patients at least 1 urine cytology
      study was done less than 3 months before bladder biopsy. We examined 272 bladder
      biopsies (several patients underwent more than 1 biopsy at least 1 year apart)
      with 1 to 6 cytology studies done before biopsy. RESULTS: Cytology results were
      classified as negative-no malignant cells, inflammation or benign urothelial
      cells, reactive-atypia or atypical reactive and suspicious-atypical suspicious,
      keratinizing squamous metaplasia, suspicious for cancer, cancer or dysplastic. A
      total of 960 cytology specimens was obtained before the 272 biopsies (average 3
      before each biopsy). Of 17 patients with cancer 12 had at least 1 prior
      suspicious urine cytology result. The sensitivity and specificity of cytology
      were 71 and 97%, respectively, when evaluating only patients with suspicious
      findings. CONCLUSIONS: The high sensitivity and specificity of multiple cytology
      studies in this population suggest that cytology is a useful adjunct to improve
      the detection of bladder cancer in spinal cord injured patients with chronic
      (longer than 5 years) indwelling catheters. We recommend a minimum of yearly
      cytology in all high risk spinal cord injured patients with subsequent biopsies
      in all patients with any suspicious finding.

PMID- 9146594
TI  - Squamous cell carcinoma of bladder.

PMID- 9146595
TI  - Fluorescence in situ hybridization identifies more aggressive types of primarily
      noninvasive (stage pTa) bladder cancer.
AB  - PURPOSE: We evaluated the genetic changes in cytological specimens of bladder
      cancer by fluorescence in situ hybridization, and related them to stage and grade
      of the tumor, ploidy, p53 and Ki-67 expression, and clinical outcome to determine
      a simple method to identify tumors with a poorer prognosis. MATERIALS AND
      METHODS: Using fluorescence in situ hybridization the numerical aberrations of
      chromosomes 7, 9 and 17 in barbotages and imprints of 50 patients with
      transitional cell cancer of the bladder were determined. Of the patients 29 had a
      primary stage pTa tumor, while 21 with stage pT1 or greater disease formed the
      control group. Data were compared to ploidy status, and Ki-67 and p53
      immunoreactivity. RESULTS: Repeated monosomy 9 and haploid or diploid status on
      static ploidy determination were found in patients with primary stage pTa tumors
      without recurrence. Immunoreactivity of p53 was negative in all of these
      patients, while there was a low percentage of positive staining for Ki-67.
      Patients with recurrent and progressive disease had a high incidence of trisomy 7
      and 17, aneuploid status and high positivity for both immunological markers. For
      chromosomes 7 and 17, and ploidy status bivariate analysis showed a significant
      difference. CONCLUSIONS: The evaluation of chromosomal aberrations in barbotage
      and imprint specimens clearly establishes a relationship between chromosomal
      defects and aggressiveness of the tumor. The majority of nonaggressive stage pTa
      transitional cell carcinomas can be distinguished from potentially lethal cases
      by fluorescence in situ hybridization at a diagnostic point when the grading is
      not yet prognostic.

PMID- 9146596
TI  - Risk of urethral, vaginal and cervical involvement in patients undergoing radical
      cystectomy for bladder cancer: results of a contemporary cystectomy series from
      M. D. Anderson Cancer Center.
AB  - PURPOSE: Orthotopic bladder reconstruction in women is the focus of considerable
      interest. To define suitable candidates for orthotopic reconstruction among women
      with bladder cancer, we reviewed the risk of secondary urethral, vaginal and
      cervical involvement by transitional cell carcinoma in patients who underwent
      radical cystectomy at our institution. MATERIALS AND METHODS: We retrospectively
      reviewed the charts of women who underwent radical cystectomy for primary
      transitional cell carcinoma of the bladder between 1985 and 1995. These cases
      also were reviewed pathologically. RESULTS: Of 115 patients who underwent radical
      cystectomy for transitional cell carcinoma of the bladder 9 (8%) also had
      secondary transitional cell carcinoma of the urethra, including 2 with
      concomitant involvement of the vagina or cervix. In 4 patients (3%) the vagina or
      cervix was involved but not the urethra. Vaginal and cervical invasion correlated
      with stages T3b and T4 disease (p = 0.04). By logistic regression analysis the
      sole significant risk factor for urethral involvement was bladder neck
      involvement (p = 0.0005). Unlike previous studies 2 of 9 patients with secondary
      urethral transitional cell carcinoma did not have apparent cancer at the bladder
      neck. CONCLUSIONS: We report secondary urethral involvement without apparent
      bladder neck involvement in women with transitional cell carcinoma. Women who are
      candidates for orthotopic reconstruction should undergo biopsies of the bladder
      neck and urethra as part of the preoperative evaluation. In patients with
      palpable masses (stage T3b) on bimanual examination, transvaginal biopsies should
      also be considered. Intraoperative frozen sections of the urethral and vaginal
      margins should be obtained.

PMID- 9146597
TI  - Quality of life effects of alprostadil therapy for erectile dysfunction.
AB  - PURPOSE: We evaluated the quality of life effects of self-administered
      intracavernosal injection of alprostadil sterile powder for erectile dysfunction
      when used by patients for up to 18 months. MATERIALS AND METHODS: Clinical and
      self-reported measurements were used to assess physiological and psychological
      status at baseline, and at 3, 6, 12 and 18 months for 579 patients who entered
      the self-injection phase of an open label, flexible dose clinical trial. Quality
      of life was measured using the Center for Marital and Sexual Health Sexual
      Functioning Questionnaire, which focuses on the psychosocial and physical
      dimensions of erectile dysfunction; the Brief Symptom Inventory, which measures
      mental health, and the Duke Health Profile, which measures general quality of
      life. The primary evaluations were quality of life changes from baseline to post
      initiation periods and reasons for treatment discontinuation. RESULTS: The Center
      for Marital and Sexual Health Sexual Functioning Questionnaire displayed
      improvements at all post-initiation periods in 10 questions (p < 0.001, Student's
      paired t-tests) grouped into scales representing frequency of sexual activity,
      erection, orgasm and satisfaction domains. On the Brief Symptom Inventory
      interpersonal sensitivity, anxiety and depression as well as global scores
      improved (p < 0.001). Overall mental health as measured by the Duke Health
      Profile also improved (p < 0.01) between baseline and 6 months. The reasons most
      frequently cited for treatment discontinuation were nonfirm erections and
      injection site pain. CONCLUSIONS: Clinical improvements in erectile function due
      to alprostadil therapy were associated with improvements in sexual activity,
      sexual satisfaction and overall mental health.

PMID- 9146598
TI  - The impact of aging on penile hemodynamics in normal responders to
      pharmacological injection: a Doppler sonographic study.
AB  - PURPOSE: The change in arterial flow velocity with age in patients with a normal
      response to pharmacological injection was evaluated. MATERIALS AND METHODS: We
      studied 64 patients with erectile dysfunction who responded well to
      intracavernous injection of 10 micrograms. prostaglandin E1 with well sustained
      penile rigidity for longer than 1 hour and normal cavernous arterial flow
      velocities on color Doppler ultrasonography. The men were classified into 4
      groups according to age younger than 30 years, and 30 to 39, 40 to 49 and 50
      years old or older. Flow parameters were compared. RESULTS: The statistically
      significant decreasing tendency of peak systolic velocity with age was revealed
      by a simple regression test (p = 0.003). The greatest decrease was observed
      between patients in the third and fourth decades. When comparing the peak
      systolic velocity according to timing of measurement, the greatest velocities
      occurred at later measurements after the fifth decade, while in younger patients
      these values were reached earlier. CONCLUSIONS: These data demonstrate that
      cavernous arterial flow during pharmacological erection decreases and the
      response time of the cavernous artery or tissue to a vasoactive drug becomes
      longer with age.

PMID- 9146599
TI  - Comparative study of papaverine plus phentolamine versus prostaglandin E1 in
      erectile dysfunction.
AB  - PURPOSE: We compared the efficacy and short-term adverse effects of 1 ml. 30
      mg./ml. papaverine plus 0.5 mg./ml. phentolamine versus 1 ml. 30 micrograms./ml.
      prostaglandin E1 in patients undergoing pharmacological erection testing.
      MATERIALS AND METHODS: A total of 60 patients (mean age 58 years) with a history
      of sexual erectile dysfunction longer than 6 months was randomly classified into
      6 groups to be tested 1 week apart with the 2 solutions and with placebo to
      evaluate erection response and short-term adverse effects. RESULTS: Of the
      patients tested with papaverine plus phentolamine 54% responded with erections
      adequate for penetration, compared to 50% of those tested with prostaglandin E1
      (p > 0.05). Prolonged erection occurred in 18% of patients tested with papaverine
      plus phentolamine and 15% of those tested with prostaglandin E1 (p > 0.05). Pain
      was reported by 15 and 35% of patients, respectively (p < 0.05). CONCLUSIONS: One
      ml. 30 mg./ml. papaverine plus 0.5 mg./ml. phentolamine has the same efficacy and
      equal prolonged erection rate as 1 ml. 30 micrograms./ml. prostaglandin E1 but
      the latter agent induces significantly more pain.

PMID- 9146600
TI  - Comparative results of goal oriented therapy for erectile dysfunction.
AB  - PURPOSE: Goal oriented therapy for erectile dysfunction, based on a complete
      education of the couple, was offered to 460 patients. The short-term and long
      term results of the first and second treatments selected were compared. MATERIALS
      AND METHODS: From September 1991 to March 1995, 460 patients with erectile
      dysfunction were evaluated and treated prospectively. The success of treatment,
      selected by the patient or couple, was defined as the ability to achieve and
      maintain good erections for successful coitus for at least 1 year after the start
      of therapy. Sexual satisfaction of the couple was required to confirm a
      successful outcome. RESULTS: The preferred first line of treatment by 322
      patients was pharmacotherapy, with intracavernous injections being the second
      most selected therapy (80% success rate). However, there was a high long-term
      dropout rate for intracavernous injections. Approximately 70% of the patients
      were lost to followup or refused further treatment. CONCLUSIONS: Overall, this
      prospective study showed that goal oriented therapy is initially highly
      successful. However, the long-term high dropout rate and dissatisfaction of the
      couple cast doubt about the efficacy of the present treatment options.

PMID- 9146601
TI  - Impotence.

PMID- 9146602
TI  - Formation of reactive oxygen species by spermatozoa from asthenospermic patients:
      response to treatment with pentoxifylline.
AB  - PURPOSE: We determined the incidence of reactive oxygen species formation by
      spermatozoa from asthenospermic patients, and the relationship between reactive
      oxygen species formation and sperm motion parameters. We also assessed the
      efficacy of in vitro and in vivo pentoxifylline treatment of asthenospermic
      patients whose spermatozoa generated high reactive oxygen species levels.
      MATERIALS AND METHODS: Reactive oxygen species formation by spermatozoa from
      asthenospermic patients and fertile volunteers was measured by chemoluminescence.
      Reactive oxygen species formation by the sperm preparations was investigated
      without stimulation (steady state), or after stimulation with N-formyl-methionyl
      leucyl-phenylalanine (f-MLP) or phorbol-12-myristate-13-acetate. Spermatozoa from
      15 asthenospermic patients whose spermatozoa produced high levels of reactive
      oxygen species at steady state were treated in vitro with pentoxifylline to
      determine its effect on reactive oxygen species generation and sperm motion
      parameters. These same 15 patients and 18 with asthenospermia whose spermatozoa
      did not produce reactive oxygen species at steady state were treated with
      pentoxifylline at 2 different dosages (300 and 1,200 mg. daily) to determine its
      effect on reactive oxygen species generation, sperm motion parameters and sperm
      fertilizing ability in vivo. RESULTS: When reactive oxygen species formation was
      detected in the steady state that was not stimulated by f-MLP, the source of
      reactive oxygen species could be attributed to the spermatozoa themselves.
      Spermatozoa from 15 of 71 asthenospermic patients generated reactive oxygen
      species at steady state. Pentoxifylline decreased reactive oxygen species
      generation by spermatozoa in these patients, and preserved the decrease of
      curvilinear velocity and beat cross frequency for 6 hours in vitro. For these
      patients orally administered pentoxifylline failed to decrease reactive oxygen
      species generation by spermatozoa, and had no effect on sperm motility, sperm
      motion parameters and sperm fertilizing ability at low dosage (300 mg. daily).
      However, it increased motility and beat cross frequency at high dosage (1,200 mg.
      daily) but it had no effect on sperm fertilizing ability. CONCLUSIONS:
      Stimulation of sperm preparations with f-MLP can identify the source of reactive
      oxygen species generated at steady state. Among asthenospermic patients there
      were some whose spermatozoa produced detectable steady state levels of reactive
      oxygen species. In this group pentoxifylline appeared to be effective for
      decreasing reactive oxygen species formation and preserving sperm motion
      parameters in vitro. Orally administered pentoxifylline had no effect at low
      dosage but it increased sperm motility and some sperm motion parameters without
      altering sperm fertilizing ability at high dosage.

PMID- 9146603
TI  - Electroejaculation versus vibratory stimulation in spinal cord injured men: sperm
      quality and patient preference.
AB  - PURPOSE: We compared semen quality and patient preference between penile
      vibratory stimulation and electroejaculation in spinal cord injured men.
      MATERIALS AND METHODS: We treated 11 spinal cord injured men with penile
      vibratory stimulation and electroejaculation in random order. End points examined
      were semen analysis, sperm functional assessment, and patient pain scores (1 to
      10) and preferred procedure. Differences between the procedures were determined
      with the paired Student t test. RESULTS: There was no difference in antegrade
      sperm count but penile vibratory stimulation specimens had greater motility (26.0
      versus 10.7%), viability (25.2 versus 9.7%) and motile sperm count (185.0 x 10(6)
      versus 97.0 x 10(6)). The retrograde sperm count was greater (but not
      significant) in electroejaculation patients. The total (antegrade plus
      retrograde) and motile sperm counts were not different. There was no difference
      in immunobead test (all negative), cervical mucus penetration or sperm
      penetration assay, although the percent hamster egg penetration approached
      significance (53.7% for penile vibratory stimulation versus 22.1% for
      electroejaculation, p = 0.06). There was no difference in the peak blood
      pressures and no complications were noted. Pain scores were significantly greater
      for electroejaculation compared to penile vibratory stimulation (5.2 versus 1.7,
      respectively). All patients preferred penile vibratory stimulation. CONCLUSIONS:
      There was a slight advantage in sperm quality and a high patient preference in
      favor of penile vibratory stimulation. Penile vibratory stimulation should be
      attempted first to induce ejaculation in spinal cord injured men, with
      electroejaculation reserved for failures.

PMID- 9146604
TI  - Sperm from spinal cord injured men lose motility faster than sperm from normal
      men: the effect is exacerbated at body compared to room temperature.
AB  - PURPOSE: We investigated if sperm from spinal cord injured men lose motility and
      viability faster than sperm from normal men, and if there is an effect of
      temperature on these parameters. MATERIALS AND METHODS: Identical aliquots of
      fresh antegrade semen from 10 spinal cord injured men and 9 normal controls were
      stored at room temperature (23C) or body temperature (37C). Sperm motility and
      viability were measured at 0, 2, 4, 6 and 8 hours after semen collection.
      RESULTS: Sperm motility, particularly rapid linear motility, decreased faster in
      specimens from spinal cord injured men compared to normal controls. This effect
      was exacerbated at 37C. Heat did not affect the degradation of sperm motility in
      specimens from normal men. The percent of dead sperm in specimens from spinal
      cord injured men was significantly greater than that in normal men at all time
      points. However, the rate of cell death was not faster than normal with time or
      heat. CONCLUSIONS: When using sperm from spinal cord injured men for purposes of
      insemination or experimentation the rapid loss of motility must be considered,
      particularly when stored at body temperature.

PMID- 9146605
TI  - Postmortem sperm procurement.
AB  - PURPOSE: We determined the prevalence of requests for postmortem sperm
      procurement and the degree to which procurement is performed by those working in
      the field of infertility. MATERIALS AND METHODS: Structured telephone interviews
      were conducted with personnel at 273 assisted reproductive facilities in the
      United States and Canada. The number of facilities reporting requests and the
      number of facilities reporting that they performed the procedure were determined.
      RESULTS: The prevalence of requests for postmortem sperm procurement was much
      greater than initially anticipated. A total of 82 requests was reported at 40
      facilities in 22 different states between 1980 and 1995. More than half of the
      reported requests (43) were made between 1994 and 1995. Of the 82 requests 25
      were honored at 14 facilities in 11 different states. No requests or procedures
      were reported from Canada. CONCLUSIONS: Medical advances in postmortem sperm
      procurement, cryopreservation and in vitro fertilization permit retrieval of
      sperm after death for various purposes, including posthumous fatherhood. There
      are no explicit ethical guidelines, legislation or relevant case law, and
      fertility specialists must confront these issues before proceeding in a field
      fraught with moral and policy uncertainties.

PMID- 9146606
TI  - Reproductive urology.

PMID- 9146607
TI  - The American Urological Association symptom index for benign prostatic
      hyperplasia as a function of age, volume and ultrasonic appearance of the
      prostate.
AB  - PURPOSE: Our study was conducted to reveal quantitatively the relative effects of
      age and ultrasonic appearance of benign prostatic hyperplasia (BPH) on urinary
      symptoms as evaluated by the American Urological Association (AUA) symptom index
      score. MATERIALS AND METHODS: In 929 examinees (732 with a normal prostate and
      197 with BPH) on a mass screening program for prostatic diseases using
      transrectal ultrasonography in Japan, the AUA symptom score was compared to age,
      prostatic volume and presumed circle area ratio using simple and multiple
      regression analyses. RESULTS: Simple regression analysis demonstrated the symptom
      score to correlate significantly with age (R = 0.162, p < 0.0001), prostatic
      volume (R = 0.072, p = 0.0281) and presumed circle area ratio (R = 0.150, p <
      0.0001). However, multiple regression analysis demonstrated that age and presumed
      circle area ratio were significant independent determinants of the total symptom
      score. Among 7 symptoms included in the AUA symptom index weak stream and
      hesitancy scores were not influenced by age, prostatic volume or presumed circle
      area ratio. CONCLUSIONS: As a parameter representing the degree of BPH in terms
      of the severity of urinary symptoms, presumed circle area ratio was preferable to
      prostatic volume. Regression analyses confirmed again that the AUA symptom index
      was influenced considerably by age and was not specific to BPH.

PMID- 9146608
TI  - Prostate specific antigen in benign prostatic hyperplasia: purification and
      characterization.
AB  - PURPOSE: The ratio of free-to-total prostate specific antigen (PSA) in serum is
      greater in patients with benign prostatic hyperplasia (BPH) than in those with
      prostate cancer, and it provides a means of partially discriminating these 2
      diseases. To understand the molecular mechanism of why the free-to-total PSA
      ratio is greater in BPH than in prostate cancer we analyzed PSA obtained directly
      from nodules of BPH tissue. MATERIALS AND METHODS: PSA from BPH nodule fluids was
      first purified by gel filtration and ion exchange chromatography. Purified BPH
      PSA was characterized by gel electrophoresis, enzyme assay and N-terminal
      sequence analysis of the amino acids. RESULTS: A single band at 30 kDa. on sodium
      dodecyl sulfate polyacrylamide gel electrophoresis under nonreducing conditions
      was identical to that of seminal fluid PSA. Under reducing conditions most BPH
      PSA was degraded, whereas most seminal fluid PSA existed as an intact molecule.
      BPH PSA had multiple internal cleavages in addition to the common cleavage site
      between lysines 145 and 146 of seminal fluid PSA. Cleavage sites at C-terminals
      of histidine 54 and phenylalanine 57 were also detected. Enzymatic activity
      studies with different substrates showed that PSA from seminal fluid and BPH
      nodules had similar specific trypsin-like activity. However, BPH PSA had much
      lower specific chymotrypsin-like activity than seminal fluid PSA. N-terminal
      sequence analysis showed that BPH PSA was neither in the pre-proenzyme form (261
      amino acids) nor the zymogen proenzyme form (244 amino acids) of PSA, both of
      which are known precursors of mature PSA (237 amino acids). CONCLUSIONS: Most PSA
      in BPH nodules is in the nicked form with low chymotrypsin-like activity. When it
      leaks into the circulation it will form fewer PSA-antichymotrypsin complexes and
      more will remain in the free form. We predict that a protease with trypsin-like
      activity in BPH nodule fluid is probably responsible for the nicked form of BPH
      PSA. These findings suggest that antibodies produced against PSA in BPH nodules
      may be useful in discriminating prostate cancer from BPH.

PMID- 9146609
TI  - Prostate tissue composition and response to finasteride in men with symptomatic
      benign prostatic hyperplasia.
AB  - PURPOSE: We sought to quantify prostate tissue changes induced by finasteride and
      to identify a predictor of finasteride response in men with symptomatic benign
      prostatic hyperplasia (BPH) via a randomized, placebo controlled, double-blind
      clinical trial. MATERIALS AND METHODS: Men with symptomatic BPH (52 to 78 years
      old) were randomly assigned to 6 months of treatment with finasteride (26) or
      placebo (15). Outcome measures were clinical (urinary symptom score and flow
      rate), chemical (serum prostate specific antigen and dihydrotestosterone levels),
      volumetric (transrectal ultrasound, and magnetic resonance imaging for whole and
      zonal prostate volumes) and histological (morphometry of prostate sextant
      biopsies, separated into inner and outer gland segments, to measure the percent
      epithelium, stroma and glandular lumen). RESULTS: In the finasteride group we
      found a suggestion of decreasing symptom scores and increasing flow rates (not
      significant) with significant decreases (p < 0.01) in prostate specific antigen
      (48%), dihydrotestosterone (74%) and prostate volume (21%). Finasteride treatment
      induced a 55% decrease in inner gland epithelium (p < 0.01) with little effect on
      stroma or lumina. We also found a linear correlation between pretreatment inner
      gland epithelial content and prostate volume decrease induced by the drug (tau =
      0.58, p = 0.01). CONCLUSIONS: Finasteride treatment results in a major
      suppression of prostate epithelium, which is most pronounced in the inner gland.
      Moreover, a finasteride induced prostate volume decrease was predictable by
      quantification of epithelial tissues of the inner gland. These data lend
      additional support to the emerging concept of transition zone primacy in
      symptomatic BPH.

PMID- 9146610
TI  - Biological variation of total, free and percent free serum prostate specific
      antigen levels in screening volunteers.
AB  - PURPOSE: We determined the biological variation of the total, free and percent
      free serum prostate specific antigen (PSA) in men 50 years old or older.
      MATERIALS AND METHODS: Between July 1995 and February 1996 we studied 84 healthy
      men from our PSA screening study to determine biological variation by calculating
      the coefficients of variation of 3 PSA measurements on blood samples drawn from
      each subject 2 weeks apart. RESULTS: The mean coefficients of variation for
      total, free and percent free serum PSA were 15, 17 and 14%, respectively. Age,
      total PSA and ejaculation were not confounding factors in this analysis (that is
      multivariate R2 less than 5% for all indexes). CONCLUSIONS: There is a mean
      variation of approximately 15% in measurements of total, free and percent free
      PSA that does not appear to be significantly affected by age and total PSA level.

PMID- 9146611
TI  - Biological variation of prostate specific antigen levels in serum: an evaluation
      of day-to-day physiological fluctuations in a well-defined cohort of 24 patients.
AB  - PURPOSE: We evaluated the daily biological variation of serum prostate specific
      antigen (PSA) concentrations to determine the critical difference required
      between 2 consecutive PSA measurements that would indicate a significant
      elevation. MATERIALS AND METHODS: A total of 24 men, grouped according to
      clinical diagnosis and PSA, underwent phlebotomy for 10 consecutive weekdays.
      Duplicate serum samples were measured using 3 separate lots of Tandem-E and IMx
      PSA assays. The biological variation was calculated and the 2 PSA assay systems
      were compared. The critical difference was examined to determine the percent
      elevation necessary to indicate (with 95% confidence) that PSA had increased
      beyond what would be expected from biological and analytical variation. RESULTS:
      The biological variation, defined in terms of percent coefficient of variation,
      had a log-normal distribution with a geometric mean of 7.3% coefficient of
      variation and a 95th percentile value of 19.2% coefficient of variation using the
      Tandem-E PSA assay. Assuming an analytical variation of 5% coefficient of
      variation, the median critical difference was 20.5% and the 95th percentile
      critical difference was 45.8%. There was no significant difference between the 2
      PSA assay systems in biological variation. However, PSA concentrations measured
      by the IMx assay were consistently lower compared to values measured by the
      Tandem-E assay. CONCLUSIONS: Characterizing the biological variation of serum PSA
      assists in evaluating the significance of changes in serial PSA measurements. The
      degree of biological variation differs among patients, such that an increase
      between 2 consecutive PSA levels that is less than 20 to 46% may be due to
      biological and analytical variation. These data influence interpretation of
      repeated measurements of serum PSA with time.

PMID- 9146612
TI  - The free-to-total prostate specific antigen ratio improves the specificity of
      prostate specific antigen in screening for prostate cancer in the general
      population.
AB  - PURPOSE: The ratio between free and total prostate specific antigen (PSA) in
      serum improves the specificity of total serum PSA for the detection of prostate
      carcinoma in select populations. The value of the free-to-total PSA ratio for a
      PSA of 4.0 to 10.0 ng./ml. was analyzed in a screening population. MATERIALS AND
      METHODS: From 4,800 participants 55 to 76 years old 977 biopsies were obtained
      because of an abnormal digital rectal examination, suspicious transrectal
      ultrasonography and total serum PSA 4.0 ng./ml. or more. Of 191 patients with
      prostate carcinoma detected 101 had a serum PSA of 4.0 to 10.0 ng./ml. and 54 of
      them underwent radical prostatectomy. A free-to-total PSA ratio of 0.20, age
      specific PSA reference ranges and a PSA density of 0.12 ng./ml./cc were evaluated
      for the ability to increase the specificity of total serum PSA in predicting
      positive prostate biopsy results. RESULTS: Receiver operating characteristics
      curves for the free-to-total PSA ratio showed a significant increase in
      specificity compared to PSA. Retrospective application of age specific PSA
      reference ranges, the free-to-total PSA ratio and the PSA density decreased the
      number of biopsies significantly by up to 40% in our study, with a decrease in
      cancer detection rate of 12%. When used in combination with digital rectal
      examination, the pathological stage of undetected carcinomas appeared favorable.
      CONCLUSIONS: The free-to-total PSA ratio may be used to decrease biopsies in
      patients with an intermediate PSA of 4.0 to 10.0 ng./ml.

PMID- 9146613
TI  - Prostate specific antigen.

PMID- 9146615
TI  - Can androgen deprivation with leuprolide be predicted from histology alone? If
      not, why not?
AB  - PURPOSE: Androgen deprivation therapy with analogues of luteinizing hormone
      releasing hormone produces distinctive histological changes in neoplastic and
      nonneoplastic prostate tissue. Others have described these features in cases in
      which treatment status was known. To our knowledge the specificity and
      sensitivity of luteinizing hormone-releasing hormone effects based only on
      histology and possible reasons for interobserver variation have not been
      addressed previously. MATERIALS AND METHODS: Slides from 97 prostatectomies
      performed in a 3-year period were reviewed by 2 observers blinded to knowledge of
      previous hormonal treatment. The observers evaluated each case, recording the
      presence or absence of 14 features associated with androgen deprivation therapy,
      and then made an overall assessment regarding treatment status. RESULTS: Of the
      97 patients 31 had received androgen deprivation therapy with the luteinizing
      hormone-releasing hormone agonist leuprolide. A luteinizing hormone-releasing
      hormone effect was identified by the 2 observers in 26 and 28, respectively, of
      the 31 cases (83.9 versus 90.3% sensitivity and 92.4 versus 80.3% specificity).
      Including focal changes as consistent with androgen deprivation therapy increased
      sensitivity but decreased specificity. Of the 14 features 12 had a significant
      association for predicting treatment status. CONCLUSIONS: Interobserver
      variations in interpretation occurred although both examiners were experienced in
      the evaluation of luteinizing hormone-releasing hormone effects and they used
      exactly the same criteria. These variations were apparently due to differences in
      the value (mental weight) given by each observer to the features assessed in each
      case. Predicting treatment status was optimized by noting a luteinizing hormone
      releasing hormone effect only when changes were diffuse, improving specificity
      significantly with only a modest decrease in sensitivity.

PMID- 9146614
TI  - Antibiotic prophylaxis in ultrasound guided transrectal prostate biopsy.
AB  - PURPOSE: A retrospective review of a large group of transrectal ultrasound guided
      biopsies was performed to determine the symptomatic urinary tract infection rate
      associated with a consistent and defined antibiotic prophylaxis regimen.
      MATERIALS AND METHODS: A total of 4,439 biopsies was performed using an 18 gauge
      needle with ultrasound guidance. Patients were treated with 500 mg. ciprofloxacin
      twice daily for 8 doses beginning the day before biopsy. RESULTS: Of 5
      symptomatic urinary tract infections noted 3 were complicated. CONCLUSIONS: These
      data demonstrate the low infection rate associated with this prophylaxis regimen.

PMID- 9146616
TI  - Prospective evaluation of men with stage T1C adenocarcinoma of the prostate.
AB  - PURPOSE: The pathological characteristics of stage T1c cancers in the era of
      widespread prostate specific antigen (PSA) testing were determined, and the
      ability of pretreatment parameters to predict tumor significance in men with
      stage T1c disease was evaluated. MATERIALS AND METHODS: Of 336 men with stage T1c
      prostate cancer seen between 1994 and 1996, 240 (71.4%) were treated with radical
      prostatectomy, 20 (6%) with radiation therapy and 76 (22.6%) expectantly.
      Recommendations for treatment were based on previously determined criteria
      predictive of a significant stage T1c cancer (more than 0.2 cm.3): 1) PSA density
      0.15 ng./ml./gm. or more, 2) Gleason score 7 or greater, 3) 3 or more cores
      involved with cancer, or 4) 50% or more involvement of any core with cancer.
      Pathological evaluation of prostatectomy specimens allowed classification of
      tumors as insignificant (confined tumor smaller than 0.2 cm.3 with a Gleason
      score of less than 7), minimal (confined tumor 0.2 to less than 0.5 cm.3 with a
      Gleason score of less than 7), moderate (0.5 cm.3 or larger disease, or capsular
      penetration with a Gleason score of less than 7) and advanced (capsular
      penetration with a Gleason score of 7 or more, or positive margins, seminal
      vesicles or lymph nodes). Pathological characteristics of tumors in this series
      were compared to a previous series of 157 men with stage T1c cancers who
      underwent radical prostatectomy between 1988 and 1992. RESULTS: Of 240 men who
      underwent radical prostatectomy tumors were insignificant in 40 (17%), minimal in
      29 (12%), moderate in 124 (52%) and advanced in 47 (19%). An increase in organ
      confined cancers (51 to 72%) and a decrease in positive margins (17 to 8%) were
      noted when comparing stage T1c series (1988 to 1992 versus 1994 to 1996) but the
      percentage of insignificant tumors remained stable (16 versus 17%) between
      series. Ultrasound and sextant biopsies were available for review in 72 cases
      (current series). If the pretreatment criteria used to recommend therapy
      suggested significant tumor (64 cases) then insignificant tumor was present in
      only 10 (16%). If pretreatment criteria suggested insignificant tumor (8 cases),
      insignificant or minimal tumor was present in 6 (75%) and moderate organ confined
      disease was present in 2 (25%). The absence of a lesion on ultrasound and
      measurement of total length of cancer within the biopsy specimen were not
      predictive of an insignificant tumor. CONCLUSIONS: In a nonscreened population
      stage T1c cancers are being discovered earlier with widespread PSA testing. Even
      with the detection of earlier cancers we demonstrated that it is possible to
      minimize the number of patients with small tumors who will undergo radical
      prostatectomy using pretreatment criteria to counsel men regarding appropriate
      management options.

PMID- 9146617
TI  - Transvesical prostatectomy in elderly patients.
AB  - PURPOSE: We assessed the results of transvesical prostatectomy in patients older
      than 80 years. MATERIALS AND METHODS: We studied 98 patients 80 to 90 years old
      who underwent transvesical prostatectomy between 1986 and 1993, including those
      with a large prostate (preoperative estimated weight more than 80 gm.), numerous
      or large cystolithiasis and large bladder diverticulum, which are indications for
      open prostatectomy. Clinical data were obtained by chart review. RESULTS: The
      indications for surgery were urinary retention in 53 patients (54%), severe
      obstructive urinary symptoms in 18 (18.4%), cystolithiasis in 17 (17.3%),
      prostatic bleeding in 10 (10.2%) and bladder diverticulum in 2 (2%). Accompanying
      diseases were present in 69 patients (70.6%), including ischemic heart disease in
      41 (42%), diabetes mellitus in 17 (17.3%) and arterial hypertension in 14
      (14.3%). A total of 59 patients (60.2%) underwent surgery while under general
      anesthesia and 39 (39.8%) received regional anesthesia. Average operative time
      was 62 minutes. Of the patients 40 (40.8%) received 1, 14 (14.3%) received 2 and
      2 (2%) received 4 units of blood. No postoperative deaths or life threatening
      complications were noted. The immediate postoperative complications included
      urinary tract infection in 20 patients (20.5%), wound infection in 3 (3.0%) and
      orchiepididymitis in 3 (3.0%). Postoperative mild to moderate incontinence was
      noted in 2 patients (2.0%). Bladder neck constriction and urethral strictures
      occurred in 4 (4.1%) and 3 (3.0%) patients, respectively. CONCLUSIONS:
      Transvesical prostatectomy can be performed safely in elderly patients with a low
      morbidity rate.

PMID- 9146618
TI  - Has there been a recent shift in the pathological features and prognosis of
      patients treated with radical prostatectomy?
AB  - PURPOSE: We determined if there has been a significant change in pathological
      stage or prognosis of patients with clinically localized prostate cancer treated
      with radical prostatectomy between 1983 and 1995. During this period the methods
      of detection of prostate cancer changed to include, in recent years, a large
      proportion of nonpalpable cancers detected by prostate specific antigen (PSA).
      MATERIALS AND METHODS: The method of diagnosis, pathological features and
      prognosis (PSA detected progression-free probability) of 754 consecutive patients
      treated by 1 surgeon for clinical stages T1 to 3NXMO prostate cancer from 1983 to
      1995 were analyzed by year of diagnosis. RESULTS: There was a marked increase in
      the annual number of radical prostatectomies performed with time. The proportion
      of cancers initially detected by transurethral resection decreased markedly after
      1989. Beginning in 1990 nonpalpable cancers detected by PSA increased
      substantially to 52% by 1995. However, there was no significant change in
      preoperative serum PSA, tumor volume or pathological stage during the study
      period. The proportion of patients with well differentiated cancer decreased
      somewhat, while those with moderate to poorly differentiated (Gleason sum 7)
      cancers increased significantly after 1991. There was no increase with time in
      the proportion of patients with a small (less than 0.5 cm.3), well or moderately
      differentiated (Gleason grades 1 to 3) cancer confined to the prostate (an
      indolent or clinically unimportant cancer) but fewer patients in recent years had
      an advanced cancer (established extraprostatic extension with a positive surgical
      margin, seminal vesicle invasion or lymph node metastases). The actuarial
      probability of progression after surgery was similar for patients treated from
      1983 to 1987, 1988 to 1991 and 1992 to 1995. CONCLUSIONS: Despite marked changes
      in the number of patients treated each year and the method by which cancers were
      first detected, we found no change in pathological stage or prognosis
      (progression rate) for patients treated with radical prostatectomy between 1983
      and 1995. Despite concerns that the increased detection of prostate cancer could
      lead to many more patients being treated unnecessarily for small, indolent
      cancers, we found no increase in the proportion of such cancers with time.

PMID- 9146619
TI  - Use of radical prostatectomy among Medicare beneficiaries before and after the
      introduction of prostate specific antigen testing.
AB  - PURPOSE: We monitored the use of radical prostatectomy in medicare beneficiaries
      before and after the introduction of prostate specific antigen (PSA) testing.
      MATERIALS AND METHODS: Radical prostatectomies performed on medicare
      beneficiaries between 1984 and 1995 were identified through the medicare claims
      data base. Medicare enrollment files were used to define the population at risk
      and age-adjusted rates were standardized to the 1990 United States medicare
      population. RESULTS: Rates of radical prostatectomy have steadily increased since
      1984. A sharp increase in radical prostatectomy rates followed the institution of
      PSA testing after which a prominent decrease, particularly among older age
      groups, was evident. During the peak year of 1992 the age-adjusted rates of
      radical prostatectomy for white and black men 65 to 79 years old in the United
      States were 461.2 and 294.5/100,000 men. Between 1992 and 1995 the rates of
      radical prostatectomy among white men decreased by 22, 47 and 69% for patients 65
      to 69, 70 to 74 and 75 to 79 years old, respectively. The corresponding changes
      among black men were +6, -18 and -47%, respectively. Differences in the age
      adjusted rates between white and black men have narrowed in recent years, ranging
      from 166.7 (1992) to 29.7 (1995)/100,000 men. CONCLUSIONS: Recent years have been
      marked by a rapid increase in the use of radical prostatectomy, which peaked in
      1992. Subsequent to 1992 a sharp decrease occurred, which was particularly
      evident in older and white men. Racial differences in the use of radical
      prostatectomy have narrowed in recent years.

PMID- 9146620
TI  - Unraveling the epidemiology of prostate cancer.

PMID- 9146621
TI  - A new technique for transurethral resection of bladder tumors: rotational tumor
      resection using a new arched electrode.
AB  - PURPOSE: A new technique of transurethral resection of bladder tumors is
      described. MATERIALS AND METHODS: A 2.5 cm. papillary, sessile bladder tumor was
      treated via a rotational resection technique with a new arched electrode to
      replace longitudinal resection using a conventional loop electrode. RESULTS: This
      method was easy to perform and allowed for en bloc resection of bladder tumor.
      CONCLUSIONS: This rotational resection technique is useful for evaluation of
      pathological depth of tumors in resected specimens.

PMID- 9146622
TI  - Perineal cystoprostatectomy and ureterosigmoidostomy for invasive bladder cancer.
AB  - PURPOSE: A technique for perineal cystoprostatectomy with ureterosigmoidostomy is
      described as a minimally invasive method to treat muscle invasive bladder cancer.
      MATERIALS AND METHODS: We performed 7 perineal cystoprostatectomies. In the most
      recent case ureterosigmoidostomy performed via the perineal approach was the
      definitive method of urinary diversion. RESULTS: The operation was well tolerated
      and minimally invasive. CONCLUSIONS: Perineal cystoprostatectomy and
      ureterosigmoidostomy are effective and minimally invasive means of definitive
      therapy for muscle invasive bladder cancer.

PMID- 9146623
TI  - The value of sympathetic skin response recordings in the assessment of the
      vesicourethral autonomic nervous dysfunction in spinal cord injured patients.
AB  - PURPOSE: We assessed the degree of sparing of the descending sympathetic spinal
      tract and correlated these findings with bladder neck function in spinal cord
      injured patients. MATERIALS AND METHODS: Sympathetic skin responses of the right
      hand and foot were recorded and compared to the urodynamic findings in 27 spinal
      cord injured patients. RESULTS: All tetraplegic and paraplegic patients with a
      lesion above the T6 level who presented with bladder neck dyssynergia associated
      with autonomic hyperreflexia had abnormal sympathetic skin responses in the right
      hand and foot. All patients with a lesion below the T6 and above the T12 levels
      with an abnormal sympathetic skin response in the right foot also had bladder
      neck dyssynergia. CONCLUSIONS: Evidence is presented that the integrity of the
      descending sympathetic spinal tract is necessary for a synergic function of the
      vesicourethral complex and that sympathetic skin responses are of value in the
      diagnosis of bladder neck dyssynergia. For lesions below the T12 level other
      investigative methods to exclude bladder neck dyssynergia are necessary.

PMID- 9146624
TI  - Pseudodyssynergia (contraction of the external sphincter during voiding)
      misdiagnosed as chronic nonbacterial prostatitis and the role of biofeedback as a
      therapeutic option.
AB  - PURPOSE: Chronic lower urinary tract symptoms in young men are often attributed
      to misdiagnosed chronic nonbacterial prostatitis. We analyzed contraction of the
      external urinary sphincter during voiding (pseudodyssynergia) as an etiology of
      voiding dysfunction in men with misdiagnosed chronic prostatitis. MATERIALS AND
      METHODS: The video urodynamic studies of 43 men 23 to 50 years old with chronic
      voiding dysfunction secondary to pseudodyssynergia performed between January 1990
      and June 1996 were retrospectively analyzed. Pseudodyssynergia was diagnosed
      based on several criteria, including electrical activity of the external
      sphincter during voiding in the absence of abdominal straining, and brief and
      intermittent closing of the membranous urethra during voiding detected by
      electromyography and fluoroscopy. Patients with bacterial infection or excessive
      leukocytes in expressed prostatic secretions were excluded from the study.
      RESULTS: Of the patients 39 (91%) were firstborn men. Duration of symptoms ranged
      from 17 to 146 months (mean 43.6). Average number of previous antibiotic days
      ranged from 53 to 186 (mean 67.6). In addition, empirical trials of alpha
      blockers were unsuccessful. Mean American Urological Association symptom score
      plus or minus standard deviation was 17.5 +/- 3.7, mean maximum flow rate was
      13.3 +/- 4.2 ml. per second, mean detrusor pressure at maximum flow was 46.3 +/-
      13.7 cm. water and mean detrusor contraction duration was 132.8 +/- 27.7 seconds.
      Behavior modification and biofeedback were successful in decreasing symptoms in
      35 patients (83%) at 6 months. CONCLUSIONS: These results indicate that some men
      who are categorized as having and empirically treated for chronic nonbacterial
      prostatitis are misdiagnosed and, in fact, have functional bladder outlet
      obstruction. Urodynamics are helpful in diagnosing and predicting success with
      behavior modification and biofeedback in these patients.

PMID- 9146625
TI  - Epithelial cyst of the adrenal gland: an unusual cause of recurrent flank pain.

PMID- 9146626
TI  - A case of Cushing's syndrome due to adrenocortical carcinoma with recurrence 19
      months after laparoscopic adrenalectomy.

PMID- 9146627
TI  - Intrarenal supernumerary ovary.

PMID- 9146628
TI  - Free intraperitoneal rupture of hydronephrotic kidney.

PMID- 9146630
TI  - Acute renal failure from a subcapsular hematoma in a solitary kidney: an unusual
      complication of extracorporeal shock wave lithotripsy.

PMID- 9146629
TI  - Bilateral hydronephrosis due to intramural ureteral involvement with systemic
      sclerosis.

PMID- 9146631
TI  - Renal medullary carcinoma: a recently described highly aggressive renal tumor in
      young black patients.

PMID- 9146632
TI  - Seizures after ureteral stone manipulation with lidocaine.

PMID- 9146633
TI  - Percutaneous treatment of an intraoperative arterial injury as a result of
      endoureterotomy.

PMID- 9146634
TI  - Bilateral ureteral obstruction after asymptomatic appendicitis.

PMID- 9146635
TI  - Transitional cell carcinoma arising from a fibroepithelial ureteral polyp in a
      patient with duplicated upper urinary tract.

PMID- 9146636
TI  - Pseudotumor formation in the bladder as a late complication of total hip
      replacement.

PMID- 9146637
TI  - Early development of adenocarcinoma in a young woman following augmentation
      cystoplasty for undiversion.

PMID- 9146638
TI  - Percutaneous intravesical retrieval of a misplaced urethral stent: new
      laparoscopic instrumentation.

PMID- 9146639
TI  - Reinforcement of semirigid penile implant.

PMID- 9146640
TI  - Erosion of malleable penile prosthesis into bladder.

PMID- 9146641
TI  - Adenosquamous carcinoma of the penis.

PMID- 9146642
TI  - Elephantiasis of the legs with lichen sclerosus et atrophicus of the penis and
      scrotum.

PMID- 9146643
TI  - Idiopathic dense calcification of the seminal vesicles.

PMID- 9146644
TI  - Re: Surgical management of complex renal cysts: a series of 32 cases.

PMID- 9146645
TI  - Re: Surgical management of complex renal cysts: a series of 32 cases.

PMID- 9146646
TI  - Re: Is contralateral exploration of the kidney necessary in patients with Wilms
      tumor?

PMID- 9146647
TI  - Re: Detubularized isolated ureterosigmoidostomy: description of a new technique
      and preliminary results.

PMID- 9146648
TI  - Re: The ileal ureter neobladder is associated with a high success and a low
      complication rate.

PMID- 9146649
TI  - Re: The value of symptom score, quality of life score, maximal urinary flow rate,
      residual volume and prostate size for the diagnosis of obstructive benign
      prostatic hyperplasia: a urodynamic analysis.

PMID- 9146650
TI  - Re: Editorial comment.

PMID- 9146651
TI  - Prenatal intervention for hydronephrosis.
AB  - PURPOSE: The widespread use of prenatal ultrasound results in an increased
      recognition of fetal hydronephrosis and technological advances now make fetal
      intervention possible. However, efficacy is unknown, and there have been errors
      in diagnosis, and associated morbidity and mortality. This review focuses on the
      current status of prenatal diagnosis and management of hydronephrosis. MATERIALS
      AND METHODS: The relevant literature on prenatal physiology, prenatal diagnosis,
      experimental obstruction and clinical series of prenatal intervention was
      reviewed. RESULTS: Prenatal ultrasound is a poor discriminator of physiological
      hydronephrosis, obstruction, renal dysplasia and reflux. Persistent early onset
      oligohydramnios is the best predictor of poor neonatal outcome. New minimally
      invasive techniques may aid diagnostically but they may not improve outcome.
      Dysplasia is often present by the time hydronephrosis is detected and it is not
      reversible in experimental models. Prenatal intervention is technically feasible
      but the survival rate is only 47%, and catheter placement and open fetal surgery
      have significant fetal and maternal risks. Complications occur in up to 45% of
      fetuses. CONCLUSIONS: Prenatal intervention for hydronephrosis remains an
      experimental technique. The most important question is whether prenatal therapy
      for obstructive uropathy improves survival and decreases long-term morbidity and
      mortality in affected fetuses.

PMID- 9146652
TI  - Accuracy of renal ultrasound measurements for predicting actual kidney size.
AB  - PURPOSE: We attempted to evaluate the accuracy of renal ultrasound measurements
      for determining actual kidney size in a growing renal unit. MATERIALS AND
      METHODS: We evaluated 18 renal units in growing piglets weekly for 11 weeks on
      ultrasound. Measured parameters included length, transverse and anteroposterior
      dimensions, and volume. At 11 weeks final ultrasound measurements were obtained,
      animals were sacrificed and gross specimen measurements were made. Final
      ultrasound dimensions and serial measurements were correlated with actual size.
      Growth charts were constructed to evaluate variability between observations.
      RESULTS: Mean difference between final ultrasound renal length and actual size
      was 3.8 mm. (correlation coefficient 0.74). Serial length measurements were not
      more accurate than isolated measurements for predicting final length (correlation
      coefficient 0.34). Volume measurement was not more accurate than renal length.
      Analysis of individual growth charts revealed a significant week-to-week
      variation. CONCLUSIONS: Error in ultrasound measured kidney length can equal 1 or
      more years of growth in a child. Our results show that caution should be used
      when incorporating ultrasound measurements into surgical decision making.

PMID- 9146653
TI  - Urinary excretion of epidermal growth factor in children with reflux nephropathy.
AB  - PURPOSE: We determined urinary levels of epidermal growth factor in children with
      reflux nephropathy to evaluate the clinical significance of urinary epidermal
      growth factor. MATERIALS AND METHODS: We studied 59 boys and 41 girls 3 to 15
      years old with reflux nephropathy, and 64 boys and 36 girls 3 to 15 years old who
      were healthy. Levels of urinary epidermal growth factor were determined by
      sandwich enzyme immunoassay using spot urine samples. We also determined the
      levels of serum creatinine, urinary alpha 1-microglobulin and urinary
      microalbumin. Absolute values of function of the left and right kidneys were
      assessed by 99mtechnetium dimercapto-succinic acid (DMSA) uptake. RESULTS: Levels
      of urinary epidermal growth factor gradually decreased with age in healthy
      children. There were low levels of urinary epidermal growth factor in 20 of the
      44 patients (45%) with unilateral low DMSA uptake and 18 of the 19 (95%) with low
      total DMSA uptake (right and left uptakes). Urinary epidermal growth factor
      significantly correlated with serum creatinine (R = -0.702, p < 0.0001), urinary
      alpha 1-microglobulin (R = -0.606, p < 0.0001), urinary microalbumin (R = -0.708,
      p < 0.0001) and total DMSA uptake (R = 0.744, p < 0.0001). CONCLUSIONS: These
      results suggest that urinary epidermal growth factor may be a useful clinical
      tool to monitor functional nephron mass in children with reflux nephropathy.

PMID- 9146654
TI  - Vesicoureteral reflux in children: incidence and severity in siblings.
AB  - PURPOSE: We attempted to determine the incidence of vesicoureteral reflux in
      asymptomatic siblings of children with reflux at different ages and assess the
      incidence of renal damage in asymptomatic siblings with reflux. MATERIALS AND
      METHODS: We reviewed radionuclide cystograms of 482 consecutively referred
      siblings of children with vesicoureteral reflux, including 295 girls and 187 boys
      2 weeks to 12.8 years old (mean age 2.8 years). Ultrasonograms and renal cortical
      scintigrams of children with reflux were evaluated. All siblings were considered
      asymptomatic by the referring physicians. RESULTS: The overall incidence of
      vesicoureteral reflux was 36.5%, and the incidence in girls and boys was 39.3 and
      32.1%, respectively. Children 24 months old or younger had the highest incidence
      (45.7%) and the highest risk of bilateral reflux. From ages 25 to 72 months the
      incidence of reflux was 33.1% and in siblings older than 72 months it was 7%.
      Reflux of urine to the level of the renal pelvis was detected in 28.6% of all
      referred siblings. Renal damage was observed on sonography or scintigraphy in
      4.7% of the siblings with reflux. CONCLUSIONS: The high incidence of
      vesicoureteral reflux through age 72 months indicates that it is important to
      screen siblings of children with reflux at an early age to prevent renal damage,
      which can occur in the absence of symptomatic urinary tract infection.

PMID- 9146655
TI  - Surgical versus endoscopic correction of vesicoureteral reflux in children with
      neurogenic bladder dysfunction.
AB  - PURPOSE: We attempted to compare the efficacy of subureteral
      polytetrafluoroethylene injection and ureteral reimplantation for treating
      vesicoureteral reflux in children with neurogenic bladder dysfunction. MATERIALS
      AND METHODS: We retrospectively studied the records of all children with
      neurogenic bladder dysfunction and reflux into single collecting systems treated
      with cross-trigonal ureteroneocystostomy or subureteral polytetrafluoroethylene
      injection. Followup cystography was performed 2 months postoperatively and
      ultrasound was done twice yearly thereafter. Urodynamic data were evaluated when
      available. Success was defined as complete eradication of reflux. Data were
      stratified by procedure, patient sex, grade and laterality of reflux, and the
      presence of unilateral or bilateral reflux, and then compared using chi-square
      analysis. RESULTS: Of 85 patients (118 ureters) identified followup data were
      available in 95%. Subureteral polytetrafluoroethylene injection and
      ureteroneocystostomy were done on 60 and 47 ureters, respectively. Both groups
      were similar in mean patient age, followup and preoperative degree of reflux.
      Success rates after ureteroneocystostomy and a single injection were 84.3 versus
      56.7%. The cumulative success rate of subureteral polytetrafluoroethylene
      injection was 61% after a second injection. The success rate of
      ureteroneocystostomy was significantly greater than that of injection (p = 0.02).
      Reflux resolved in all patients in whom injection failed and who underwent
      secondary reimplantation. Successful ureteroneocystostomy was unrelated to
      patient sex, reflux grade or laterality, or bilateral versus unilateral reflux.
      Subureteral polytetrafluoroethylene injection was more likely to fail in higher
      grades of reflux (p = 0.03) but success was otherwise unrelated to other
      parameters. Failure to correct reflux was unrelated to urodynamic findings.
      CONCLUSIONS: Primary open ureteral reimplantation is more effective than
      subureteral polytetrafluoroethylene injection for correcting reflux in children
      with neurogenic bladder dysfunction. Despite controversy related to the
      appropriate injectable substance, the relative technical simplicity, outpatient
      nature, rapid recovery and potential for successful secondary reimplantation
      support a role for subureteral polytetrafluoroethylene injection in managing
      reflux in these difficult cases.

PMID- 9146656
TI  - Neurogenic bladder dysfunction due to myelomeningocele: neonatal versus childhood
      treatment.
AB  - PURPOSE: We sought to determine whether the neonatal institution of treatment of
      neurogenic bladder dysfunction in myelomeningocele patients at high risk for
      urinary tract deterioration improves renal and bladder outcome. MATERIALS AND
      METHODS: We reviewed the records of patients with bladder dysfunction believed to
      be at high risk for renal deterioration based on urodynamic studies. All patients
      were treated with clean intermittent catheterization. We compared rates of
      urinary infection, hydronephrosis, reflux, continence and surgical intervention
      in 46 patients in whom treatment was started in year 1 of life and 52 treated
      after age 4 years. RESULTS: Renal outcome was similar in both groups with
      persistent hydronephrosis in 6 of 46 patients (13%) and 7 of 52 (14%),
      respectively. However, significantly fewer bladder augmentation procedures were
      required in patients started on treatment during year 1 of life (5 of 46, 11%
      versus 14 of 52, 27%, p < 0.05). CONCLUSIONS: In addition to any psychological
      benefit, early intervention with clean intermittent catheterization in children
      with neurogenic bladder dysfunction may help to prevent irreversible bladder
      dysfunction and limit the need for bladder augmentation.

PMID- 9146657
TI  - Percutaneous cystolithotomy with endotracheal tube tract dilation after urinary
      tract reconstruction.
AB  - PURPOSE: The effectiveness of a percutaneous approach to intact removal of large
      calculi from the urinary reservoir after urinary tract reconstruction was
      reviewed. MATERIALS AND METHODS: The original site of the reservoir drainage tube
      was used for percutaneous access. After dilation of the tract to 34F a number 10
      endotracheal tube was advanced through the tract, and the balloon (diameter up to
      43 mm.) was inflated. The rigid nephroscope was then passed through the tract and
      calculi were removed intact without the need for ultrasonic or electrohydraulic
      lithotripsy. RESULTS: Removal of single or multiple reservoir calculi attempted
      in 4 patients was successful in 3. Patients were discharged home within 2 days.
      CONCLUSIONS: The technique of over dilation of the percutaneous tract allows
      removal of multiple large calculi in select patients without the need for
      lithotripsy.

PMID- 9146658
TI  - Treatment of cyclophosphamide induced hemorrhagic cystitis with neodymium:YAG
      laser in pediatric patients.
AB  - PURPOSE: Hemorrhagic cystitis is a significant and sometimes fatal complication
      of cyclophosphamide therapy. We report our recent experience using a neodymium
      (Nd):YAG laser to treat 3 pediatric patients with cyclophosphamide induced
      cystitis. MATERIALS AND METHODS: Between May 1994 and March 1995 we treated 3
      pediatric patients 6 to 8 years old with an Nd:YAG laser for severe hemorrhagic
      cyclophosphamide induced cystitis. All patients presented with gross hematuria
      and conservative measures failed. The Nd:YAG laser (20 watts and 2-second pulse
      mode) was used to fulgurate bleeding endoscopically. All patients required 2
      laser treatment sessions with a total energy range of 8,011 to 16,595 J. and
      strict parameters to avoid small bowel injury. RESULTS: All 3 patients had
      resolution of gross hematuria with Nd:YAG therapy. They were discharged home
      within 3 days after repeat laser treatment with grossly clear urine and stable
      hematocrit. At followup of 11 to 18 months the patients have grossly clear urine
      and they are free of symptoms. CONCLUSIONS: Our experience suggests that the
      Nd:YAG laser can be effective and safe for treating refractory cyclophosphamide
      induced hemorrhagic cystitis in pediatric patients.

PMID- 9146659
TI  - Periurethral collagen injection for the treatment of urinary incontinence in
      children.
AB  - PURPOSE: We assessed the efficacy and safety of periurethral collagen injection
      for urinary incontinence in children with neurogenic bladder dysfunction.
      MATERIALS AND METHODS: We treated 11 children (mean age 10.6 years) who had
      incontinence and neurogenic bladder dysfunction with periurethral injections of
      glutaraldehyde cross-linked collagen. All patients were on anticholinergics and
      all but 1 were on clean intermittent catheterization preoperatively. Four
      patients had previously undergone augmentation cystoplasty. All patients were
      assessed before and after injection with a subjective continence scale and
      multichannel urodynamics. Followup ranged from 4 to 20 months from the last
      injection. RESULTS: Mean group Valsalva leak point pressure was 34.5 cm. water.
      Four of the 11 patients had an identifiable detrusor leak point pressure. Overall
      success rate was 55% with 4 patients dry and 2 improved. Success correlated with
      a minimum increase in Valsalva leak point pressure of 20 to 25 cm. water to
      greater than 60 cm. water. Three patients had no demonstrable Valsalva leak point
      pressure after injection. All 5 patients in whom treatment failed had no change
      in Valsalva leak point pressure, including 2 with small capacity, poorly
      compliant bladders preoperatively. Because they had a component of sphincteric
      insufficiency, they underwent injection in the hope of increasing capacity with
      increased continence. In 3 patients Valsalva leak point pressure was greater than
      50 cm. water. Detrusor leak point pressure developed in 3 patients
      postoperatively, including 1 with significantly increased Valsalva leak point
      pressure. One patient with significantly increased Valsalva leak point pressure
      had urethral hypermobility postoperatively. Of the 3 patients who subsequently
      underwent augmentation cystoplasty 1 is now dry, 1 is wet and 1 died of
      complications unrelated to urological disease. Patients underwent 1 to 4
      procedures (mean 2.5). CONCLUSIONS: Periurethral collagen injection may be
      effective for urinary incontinence in patients who have adequate capacity with
      good compliance and low Valsalva leak point pressure. When there is no response
      to repeat injections or a transient response, one should consider the possibility
      of bladder decompensation.

PMID- 9146660
TI  - Failure to obtain durable results with collagen implantation in children with
      urinary incontinence.
AB  - PURPOSE: We studied the efficacy and durability of injection of glutaraldehyde
      cross-linked bovine collagen for treating urinary incontinence in children.
      MATERIALS AND METHODS: From April 1994 to July 1995, 12 boys and 8 girls 4 to 18
      years old (mean age 9.5) underwent endoscopically directed collagen injections
      into the bladder neck. Followup ranged from 9 to 23 months (mean 15.2). The
      etiology of incontinence included myelodysplasia in 12 patients,
      exstrophy/epispadias in 4, and epidural abscess, sacral agenesis, imperforate
      anus and posterior urethral valves in 1 each. RESULTS: Collagen was injected once
      in 9 patients, twice in 10 and 3 times in 1. Injected volume ranged from 3 to 18
      cc (mean 7.3). Followup urodynamic studies were available for 10 patients. Leak
      point pressure increased from 28.7 to 34.9 cm. water. One patient (5%) was dry, 5
      (25%) had improvement, 10 (50%) had transient improvement for 2 to 90 days (mean
      52) and 4 (20%) remained incontinent. Five children underwent bladder neck sling
      procedures. In 1 patient transient sciatic nerve irritation developed due to
      gluteal hematoma. CONCLUSIONS: The previously reported high success rate of
      collagen injection for urinary incontinence in children is unsupported by this
      study. Improvement in continence was temporary or inadequate in the majority of
      patients. Collagen therapy may only delay the need for surgery for managing
      organic urinary incontinence in children.

PMID- 9146661
TI  - Hypospadias repair using a modification of Beck's operation: followup.
AB  - PURPOSE: We reviewed the results of 64 cases of hypospadias repair using a
      modified Beck's operation with mobilization of the anterior urethra. MATERIALS
      AND METHODS: Patient age at correction ranged from 10 months to 12 years (mean
      3.83 years). Six patients had undergone previous surgical treatments.
      Uroflowmetry and evaluation of the urinary stream, meatus, glans, shaft and scar
      formations were used as objective criteria, and grading of management and results
      by parents was considered subjective criteria. RESULTS: An average of 2.1 years
      postoperatively 59 patients were available for this followup study. The urethral
      meatus was positioned satisfactorily onto the distal glans in all cases and no
      urethrocutaneous fistulas developed. Meatal stenosis requiring meatal dilation
      occurred in 2 boys. In 2 cases a curved glans, and curved penis and glans,
      respectively, were caused by cicatricial tissue, necessitating surgical
      correction. Uroflowmetry was possible in 46 cases (78%). One patient with meatal
      stenosis had pathological flow values. All other flow rates were within the
      normal range. In the second case of meatal stenosis objective evaluation was
      impossible. In 55 cases (93%) parents judged management and results as optimal.
      CONCLUSIONS: Mobilization of the anterior urethra for correction of distal
      hypospadias with or without chordee is highly successful, less extensive, and
      provides an excellent cosmetic and functional result with a minimal risk of
      complication. Uroflowmetry is a noninvasive, objective diagnostic tool for
      evaluating the functional results of hypospadias repair.

PMID- 9146662
TI  - Redefining the genital abnormality in the Robinow syndrome. -004.
AB  - PURPOSE: We defined the anatomical structure of the male genital abnormality in
      the Robinow syndrome. Features of this syndrome include mesomelic brachymelia of
      the arms, bifid terminal phalanges of the hands and feet, characteristic facies,
      skeletal anomalies and hypoplastic external genitalia. MATERIALS AND METHODS:
      Penile anatomy of 3 patients with the Robinow syndrome was assessed using
      computerized tomography and magnetic resonance imaging. Results were compared to
      those of 4 controls who underwent imaging for pelvic malignancies. RESULTS: Cross
      sectional imaging showed that normal penile crura were inserted onto the
      anteromedial aspect of the pubic bone. In contrast, in the Robinow syndrome they
      were inserted inferiorly and posteriorly onto the medial aspect of the ischial
      tuberosity. In addition, the crura in the Robinow syndrome extended posterior to
      a line intersecting both femoral shafts. Compared to controls, there was a
      significant gap between the symphysis pubis and dorsal aspect of the penis.
      CONCLUSIONS: The penile anomaly in the Robinow syndrome is due to abnormal
      insertion of the penile crura, resulting in a penis that appears shorter and more
      inferiorly placed between the legs.

PMID- 9146663
TI  - Effect of preoperative human chorionic gonadotropin on intra-abdominal rat testes
      undergoing standard and Fowler-Stephens orchiopexy.
AB  - PURPOSE: We attempted to determine whether preoperative human chorionic
      gonadotropin (HCG) improves fertility in intra-abdominal rat testes subjected to
      orchiopexy. MATERIALS AND METHODS: Newborn male Sprague-Dawley rats were made
      cryptorchid by bilateral gubernaculum excision at age 14 days. Select rats served
      as controls and underwent sham operations. Half of the animals were injected with
      10 international units HCG daily from days 14 to 28. On day 28 the animals were
      divided into group 1-6 that underwent sham operation with or without HCG, group 2
      6 with cryptorchidism with or without HCG, group 3-22 that underwent standard
      orchiopexy with or without HCG and group 4-22 that underwent Fowler-Stephens
      orchiopexy with or without HCG. Contralateral orchiectomy was performed
      simultaneously. On day 65 each male rat was mated with 2 female rats for 3
      ovulatory cycles. RESULTS: Mean testicular weight was markedly decreased in
      cryptorchid compared to sham operated testes (87.2 versus 344 mg./100 gm. body
      weight). Mean testicular weight was similar after standard and Fowler-Stephens
      orchiopexy. HCG enhanced mean testicular weight after sham operation, standard
      orchiopexy and Fowler-Stephens orchiopexy (403 versus 344, 193 versus 176 and 194
      versus 175 mg./100 gm. body weight, respectively) but these differences were not
      statistically significant. Fertility was present in all 6 sham operated, 0 of the
      6 cryptorchid, 1 of the 11 standard orchiopexy and 1 of the 8 Fowler-Stephens
      orchiopexy rats. Of the HCG treated animals 2 of the 8 that underwent Fowler
      Stephens orchiopexy and 1 of the 8 that underwent standard orchiopexy were
      fertile. Mean weight of the testes associated with pregnancy was significantly
      greater than those not associated with pregnancy (p < 0.001). CONCLUSIONS: The
      intra-abdominal rat testis has limited fertility potential after orchiopexy that
      is not improved with preoperative HCG. After orchiopexy fertility correlates
      closely with testicular weight.

PMID- 9146664
TI  - Vascular endothelial growth factor (VEGF) expression in prostate cancer and
      benign prostatic hyperplasia.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) is a potent inducer of
      endothelial cell growth and is expressed at elevated levels in several tumor
      types. In this study immunohistochemical localization and distribution of
      isoforms of VEGF were examined in malignant and non-malignant human prostatic
      tissues. MATERIALS AND METHODS: Immunohistochemical localization of VEGF was
      performed on thirty well, moderately and poorly differentiated stage D2 prostate
      cancer specimens and twenty benign prostatic hyperplasia (BPH) specimens. VEGF
      mRNA was determined by polymerase chain reaction and VEGF protein isoforms were
      detected by Western blotting of prostate cancer and BPH specimens. RESULTS:
      Cytoplasmic immunoreactivity for VEGF was detected in tumor cells and peritumoral
      stromal cells of prostate cancer specimens and in non-malignant glandular
      epithelial cells and interglandular stromal cells in BPH specimens. Staining was
      focal with areas of strongly to weakly stained cells adjacent to negatively
      staining areas. mRNA's for VEGF121, VEGF165 and VEGF189 were present in all
      benign and malignant prostate specimens. VEGF protein isoforms of molecular sizes
      corresponding to VEGF165 and VEGF189 were detected in cytosolic extracts of
      prostate cancers and BPH specimens by Western blotting. In addition, two novel
      higher molecular weight immunoreactive bands were detected in the prostate
      specimens. CONCLUSIONS: Widespread distribution of VEGF in prostate cancers and
      BPH specimens suggest that the VEGF165, VEGF189 isoforms and novel 90 and 110 kD
      forms detected may contribute to the establishment or progression of these
      conditions.

PMID- 9146665
TI  - Vascular endothelial growth factor (VEGF) expression in human prostate cancer: in
      situ and in vitro expression of VEGF by human prostate cancer cells.
AB  - PURPOSE: A growing body of literature supports the role of angiogenesis in the
      development and spread of a variety of human cancers including prostate cancer
      (Pca). Angiogenesis is controlled by chemical signals known as angiogenic factors
      (AF) however, little is known about angiogenesis factors in prostate cancer. We
      evaluated the in situ and in vitro expression of vascular endothelial growth
      factor (VEGF), a potent angiogenic factor, in archival prostate cancer specimens
      and prostate cancer cell cultures during unstimulated and cytokine stimulated
      conditions. METHODS: Ex-vivo studies involved immunohistochemical analysis for
      VEGF expression and distribution in 25 archival specimens including, prostate
      cancer, benign prostatic hyperplasia (BPH) and normal prostate tissue. In-vitro
      studies utilized prostate cancer cells (DU-145) grown in culture and stimulated
      with cytokines thought to induce VEGF (i.e. IL-1 alpha, IL-1 beta, TNF-alpha and
      TNF-beta). Cell culture supernatants were analyzed by ELISA for VEGF levels.
      RESULTS: Immunohistochemical studies demonstrated that in 20 of 25 specimens
      prostate cancers cells stained positively for VEGF. BPH and normal prostate cells
      displayed little staining for VEGF. DU-145 prostate cancer cells produced low
      levels of VEGF in unstimulated conditions. Induction of DU-145 cells with
      cytokines resulted in differential stimulation whereby TNF was a potent inducer
      of VEGF, and IL-1 produced lesser but statistically significant increases in VEGF
      expression. CONCLUSIONS: Our immunohistochemical results indicate that
      significant levels of VEGF are present in prostate cancer, but not in BPH or
      normal prostate cells in-vivo. In-vitro studies suggest that differential
      regulation of angiogenesis factor expression by IL-1 and TNF occurs in prostate
      cancer. Identifying the angiogenesis factors involved in prostate cancer growth
      and understanding their regulation will lead to the development of anti
      angiogenic strategies useful for diagnostic studies and therapeutic
      interventions.

PMID- 9146666
TI  - Gene expression and autoradiographic localization of endothelin-1 and its
      receptors A and B in the different zones of the normal human prostate.
AB  - PURPOSE: To investigate the gene expression and tissue distribution of prepro
      Endothelin-1 (ET-1), Endothelin Converting Enzyme (hECE-1), and ETA and ETB
      receptors in the central (CZ), transition (TZ) and peripheral (PZ) zones of
      normal human prostates. MATERIALS AND METHODS: Sections of the different zones of
      histologically normal prostates from 35 year-old men were obtained and
      autoradiographically studied with 125I ET-1 with and without the ETA antagonist
      BQ-123, the ETB agonists sarafotoxin 6C, and excess cold ET-1. Specimens from PZ
      and CZ and DU145 and PC3 human prostate cancer cell lines were also investigated
      by reverse transcription (RT)-PCR. RESULTS: The mRNAs of all genes were detected
      in all specimens examined. No ETB expression was found in either cell lines.
      Specific intense 125I ET-1 binding with clear-cut differences among zones was
      found. In the CZ the main subtype in the glandular stroma and epithelium was the
      ETA and ETB, respectively, in the PZ the opposite was true. In PZ, the ETA
      receptors were detected on the glandular epithelium; in the TZ both receptor
      subtypes were only in the stroma. CONCLUSIONS: These receptors' zonal
      distribution differences may be relevant for the pathogenesis of BPH and
      prostatic cancer.

PMID- 9146667
TI  - The cynomolgus monkey prostate under physiological and hypogonadal conditions: an
      ultrasonographic study.
AB  - PURPOSE: Although the prostate of the cynomolgus monkey has been shown to be a
      particularly suitable model for the human, in vivo data on this organ are hardly
      available. We therefore applied transrectal ultrasonography to the investigation
      of the physiology and pathophysiology of monkey prostate under normogonadotropic
      and hypogonadal conditions in vivo. MATERIALS AND METHODS: Five intact and 7 long
      term castrated monkeys were analysed repeatedly for assessment of the feasibility
      and variability of the method. In addition, cross-sectional evaluation was
      performed on 30 intact monkeys of various ages and on 7 long-term castrated
      monkeys. Finally, the vehicle (n = 5) controlled effects of androgen deprivation
      treatment with the GnRH antagonist cetrorelix (n = 4) for 25 days followed by
      semicastration at day 16 and full castration on day 25 were examined and prostate
      size was followed thereafter. RESULTS: The monkey prostate shows an ellipsoid
      shape and ultrasonic appearance similar to the human prostate. Variability in 5
      intact monkeys (mean +/- SE = 4.67 +/- 0.55 ml.) and 7 long-term castrated
      monkeys (0.88 +/- 0.08 ml.) was 8.5% and 5.6% respectively. In intact animals a
      linear correlation between age and prostate size/animal surface area was found (p
      = 0.0001). Prostate size in castrated animals was reduced (p < 0.001) compared to
      intact animals. In the experimental study, GnRH antagonist led to a significant
      reduction of prostate volume and testosterone levels compared to the vehicle
      group, while semicastration had no influence. Following removal of the second
      testis a further decrease of prostate volume was seen (p < 0.0001). When
      compared, castration and GnRH antagonist treatment induced a similar decrease of
      prostate volume over time. CONCLUSION: Transrectal ultrasonography provides a
      feasible and reproducible approach for determination of prostate size in
      cynomolgus monkeys. Castration and GnRH antagonist treatment are equally
      effective in reducing prostate size.

PMID- 9146668
TI  - Functional intactness of stimulatory and inhibitory autocrine loops in human
      renal carcinoma cell lines of the clear cell type.
AB  - PURPOSE: The aim of the present study was to analyze the contribution of
      different stimulatory and inhibitory growth factors to the deregulated
      proliferation of human RCCs. MATERIALS AND METHODS: The expression of different
      growth factors and their corresponding receptors were analyzed by Northern blot,
      FACS, ELISA and immunocytochemistry in 13 permanent human RCC cell lines of the
      clear cell type. Moreover, the functional intactness of growth factor-related
      signal transduction pathways was investigated. RESULTS: All RCC cell lines
      expressed EGF-receptor mRNA and protein and 10 cell lines secreted TGF-alpha.
      Exogeneously added TGF-alpha resulted in a significant (p < 0.05) stimulation of
      growth in 6 RCC cell lines and a significant (p < 0.05) inhibition of
      proliferation in 3 cell lines. PDGF B and the corresponding type beta receptor
      were expressed in a single cell line. mRNA expression of PDGF A and PDGF-alpha
      receptor as well as IGF-1 and its receptor could not be detected in any cell
      line. Eleven RCC cell lines expressed TGF-beta 1 mRNA and in all cell lines TGF
      beta 1 secretion into the supernatant could be demonstrated. Whereas all cell
      lines exhibited TGF-beta type II-receptor mRNA, type I-receptor mRNA could be
      detected only in 3 cell lines. TGF-beta type III-receptor was observed in 1 cell
      line. Exogeneously added TGF-beta1 resulted in a significant (p < 0.05)
      inhibition of proliferation in 7 RCC cell lines. CONCLUSION: Clear cell RCCs
      exhibit a complex and heterogeneous expression pattern for various growth factors
      and their receptors. Growth factor secretion and intact signal transduction
      pathways in most clear cell RCCs facilitate an intricate modulation of RCC growth
      by autocrine and paracrine interactions between tumor cells and host tissue.

PMID- 9146669
TI  - Basic fibroblast growth factor regulates matrix metalloproteinases production and
      in vitro invasiveness in human bladder cancer cell lines.
AB  - PURPOSE: This study was designed to investigate the effect of endogenous basic
      fibroblast growth factor (FGF-2) on matrix metalloproteinases (MMPs) production
      and in vitro invasive potential of human bladder cancer cell lines. MATERIALS AND
      METHODS: The human bladder cancer cell lines, HT1376 and KoTCC-1, were used in
      this study. The mRNA for FGF receptor has been shown to be expressed in both cell
      lines; the mRNA for FGF-2 is expressed in only KoTCC-1. The effects of FGF-2
      expression on HT1376 by gene transfection and those of FGF-2 antisense
      oligonucleotides treatment on KoTCC-1 were analyzed by zymography and in vitro
      tumor cell invasion assay. RESULTS: The introduction of human FGF-2 gene into
      HT1376 cells markedly enhanced both the MMP-2 and MMP-9 production, and the in
      vitro invasive potential was also increased. In contrast, the exposure of KoTCC-1
      cells to FGF-2 specific antisense oligonucleotides decreased the MMP-2 production
      and in vitro invasive potential, but the exposure to FGF-2 sense oligonucleotides
      did not. CONCLUSIONS: These findings suggest that FGF-2 plays an important role
      in the invasive process of human bladder cancer in part through the regulation of
      MMPs production.

PMID- 9146670
TI  - Prejunctional alpha 2-adrenoceptors inhibit nitrergic neurotransmission in horse
      penile resistance arteries.
AB  - PURPOSE: To study the influence of alpha-adrenergic stimuli on non-adrenergic non
      cholinergic (NANC) neurogenic relaxation in isolated horse penile resistance
      arteries. MATERIALS AND METHODS: Deep intracavernous penile arteries with an
      internal lumen diameter of 200-500 microns., isolated from the corpus cavernosum
      of young horses, were mounted in microvascular myographs for isometric tension
      recording and electrical field stimulation (EFS) of autonomic nerve terminals.
      RESULTS: In the presence of guanethidine (10(-5) M) and atropine (10(-7) M) tone
      of the arteries was raised by the thromboxane analogue, U46619. EFS (1, 4 and 32
      Hz) induced frequency-dependent relaxations, which were abolished in the presence
      of tetrodotoxin, while NG-nitro-L-arginine (L-NOARG, 10(-4) M) abolished the
      relaxations to EFS at 1 Hz, and significantly reduced the relaxations at 4 Hz and
      32 Hz by 82.5 +/- 10.2% and 52.9 +/- 4.7%, respectively (n = 6). EFS induced
      relaxations of a similar magnitude in penile arteries contracted with U46619 or
      the alpha 1-adrenoceptor agonist, phenylephrine, while the alpha 2-adrenoceptor
      agonist, BHT920 (10(-6) M), produced an inhibitory effect on the EFS-evoked
      relaxations which was inversely related to the stimulus frequency (1, 4 and 32
      Hz). BHT920 had no effect on the relaxations induced by exogenous nitric oxide
      (NO), added as acidified sodium nitrite (10(-6)-10(-3) M). The inhibitory effect
      of BHT920 on NANC relaxations was reversed by 10(-7) M rauwolscine. CONCLUSION:
      These results suggest that the release of a NANC neurotransmitter primarily
      thought to be NO is inhibited by stimulation of prejunctional alpha 2
      adrenoceptors in horse penile resistance arteries.

PMID- 9146671
TI  - Modulation of detrusor contraction strength and micturition characteristics by
      intrathecal baclofen in anesthetized rats.
AB  - PURPOSE: The effect of intrathecal (i.t.) baclofen in modulating the micturition
      reflexes, detrusor contraction strength, and micturition efficiency was evaluated
      in anesthetized rats. MATERIAL AND METHODS: Female Wistar rats (n = 14, 337 +/- 8
      gm.) were anesthetized with urethane (1.2 gm./kg. s.c.). Cystometrograms were
      done through a lower midline incision made to expose the bladder and a catheter
      was inserted through the bladder dome to record pressure during filling with
      saline at the rate of 0.038 ml./min. During the micturition phase of
      cystometrogram, the measurement of voided volume was made synchronously with the
      intravesical pressure. Baclofen was given intrathecally at the increasing doses
      of 0.05, 0.10, 0.5 microgram. and pressure/flow parameters were measured.
      RESULTS: The measured urodynamic parameters show that baclofen produced a
      significant dose dependent increase in bladder capacity and a decreases in
      voiding efficiency, detrusor pressure and maximum and average flow rate. Baclofen
      (0.1 microgram.) significantly decreased detrusor contractility reducing both
      Wmax from 3.7 +/- 0.1 (control) to 2.0 +/- 0.1 W/m2 and Wisv,max from 5.9 +/- 0.3
      to 5.5 +/- 0.4 W/m2 respectively. Baclofen altered the characteristic pattern of
      the micturition reflex by suppressing high frequency pressure oscillations during
      voiding which was completely abolished after 0.1 microgram. in 75% of the rats.
      Furthermore, urinary dribbling incontinence was evident at a dose of 0.5
      microgram. in 58% of all rats. CONCLUSIONS: These results demonstrate that i.t.
      baclofen has a significant inhibitory effect on the micturition reflex,
      depressing detrusor contraction strength and micturition efficiency, while
      increasing bladder capacity.

PMID- 9146672
TI  - Type III collagen messenger RNA is modulated in non-compliant human bladder
      tissue.
AB  - PURPOSE: Previous studies have demonstrated that the non-compliant bladder is
      characterized histologically by an increased deposition of extracellular matrix
      protein, especially type III collagen, in the muscle wall. We sought to determine
      if an increased tissue level of type III collagen messenger RNA (mRNA) parallels
      the observed increase in protein expression. MATERIALS AND METHODS: Using a
      reverse transcription-polymerase chain reaction (RT-PCR) quantitative technique
      we measured and compared the bladder tissue concentration of type III collagen
      mRNA between an experimental group of patients (n = 7) with urodynamically proven
      non-compliant bladders (< 12 cc/cm. H2O) and a control group (n = 8) with normal
      bladder compliance (> 20 cc/cm. H2O). RESULTS: The mean (+/-S.E.M.) of type III
      collagen mRNA level in the non-compliant group was 11.72 +/- 2.56
      attomole/milligram (amol/mg.) which was almost threefold higher than the level
      4.26 +/- 0.74 amol/mg measured in the control group. This difference was
      statistically significant (p = 0.027). CONCLUSIONS: Type III collagen mRNA levels
      are increased in the human non-compliant bladder. Therefore the accumulation of
      type III collagen protein is, in part, transcriptionally regulated.

PMID- 9146673
TI  - Image cytometry for quantitative analysis of DNA in the testes of infertile men
      with varicocele: comparison with flow cytometry.
AB  - PURPOSE: The first aim of this study is to evaluate the usefulness of image
      cytometry comparing flow cytometry to analyze the spermatogenesis using
      testicular biopsy specimens obtained from infertile male. The second is to
      investigate the spermatogenesis of infertile men with varicocele by image
      cytometry. MATERIALS AND METHODS: A total of 76 biopsy specimens of testicular
      tissue were obtained from 38 infertile men with varicocele and 6 specimens of
      normal testicular tissue controls were obtained from 6 volunteers at vasectomy.
      They were evaluated by image cytometry and pathohistological examination. Out of
      76 specimens, 21 biopsy tissues were also analyzed by flow cytometry, and the
      results by both image cytometry and flow cytometry were compared. Two specimens
      from Sertoli cell only testes were also examined by image and flow cytometry.
      RESULTS: In comparative study, image cytometry revealed a decrease in the
      proportion of haploid and diploid cells (18.8 +/- 6.6% and 32.4 +/- 7.4%), and an
      increase in that of tetraploid cells (21.8 +/- 5.6%) vs. the flow cytometry
      findings (haploid, 25.9 +/- 9.2%; diploid, 36.8 +/- 6.5% and tetraploid, 15.1 +/-
      5.9%). Image cytometric analysis of the testes of varicocele patients showed 15.9
      +/- 5.6% haploid, 31.7 +/- 7.9% diploid and 16.2 +/- 8.9% tetraploid cells in the
      left testis of infertile men, while their right testis showed 16.6 +/- 5.4%
      haploid, 30.0 +/- 7.6% diploid and 17.2 +/- 6.4% tetraploid cells. The testes of
      normal men showed 37.6 +/- 8.3% haploid, 19.4 +/- 4.8% diploid and 17.4 +/- 5.8%
      tetraploid cells. The left and the right testes of the patients with varicocele
      showed a lower proportion of haploid cells and a higher proportion of diploid
      cells vs. the testes from normal men. The proportions of the haploid and diploid
      cells are correlated with sperm concentration. CONCLUSION: Image cytometry could
      exclude interstitial cells, Sertoli cells, and sperm on the static image, so
      produced an accurate assessment of spermatogenesis. The alteration in the germ
      cell population in the testes of infertile men with varicocele suggested that the
      impairment mostly affected the cells in the meiotic stage.

PMID- 9146674
TI  - The effect of anoxia and glucose-free solutions on the contractile response of
      guinea-pig detrusor strips to intrinsic nerve stimulation and the application of
      excitatory agonists.
AB  - PURPOSE: To study the effects of anoxia and substrate depletion, both separately
      and combined, on the contractile responses of guinea-pig detrusor smooth muscle
      strips to activation of intrinsic nerves, application of agonists and
      depolarization with high potassium solution. MATERIALS AND METHODS: Bladders were
      opened and the urothelium removed. Strips of detrusor were dissected and mounted
      for tension recording in small organ baths superfused with warmed solutions of
      known composition. RESULTS: Anoxia caused a small initial reduction of the
      contractile responses which then remained constant for several hours. Glucose
      free solutions resulted in a slow progressive decline in the responses to field
      stimulation, carbachol and high potassium solution, with substantial responses
      still present after five hours. The response to ATP, however, was unaffected.
      Removal of oxygen and glucose, mimicking ischaemia, caused abolition of all
      responses within an hour. After reintroduction of normal conditions responses
      reached their maximal extent of recovery within an hour. Recovery was almost
      complete for responses to ATP and carbachol, but less so for high K+ solutions.
      Very little recovery to stimulation of intrinsic nerves was seen. CONCLUSIONS:
      The results demonstrate that phasic contractions can be fuelled almost fully by
      oxidative phosphorylation or by anaerobic glycolysis, but that in conditions
      mimicking ischaemia the intrinsic nerves are more susceptible to ischaemic damage
      than the detrusor smooth muscle.

PMID- 9146675
TI  - Antiproliferative effect of Pygeum africanum extract on rat prostatic
      fibroblasts.
AB  - The effect of a Pygeum africanum extract (Tadenan) (Pa), used in the treatment of
      micturition disorders associated with BPH, has been examined on the proliferation
      of rat prostatic stromal cells stimulated by different growth factors. EGF, bFGF,
      and IGF-I but not KGF are mitogenic for prostatic fibroblasts in culture. Pygeum
      africanum inhibits both basal and stimulated growth with IC50 values of 4.5, 7.7
      and 12.6 micrograms./ml. for EGF, IGF-I and bFGF, respectively, compared to 14.4
      micrograms./ml. for untreated cells, the inhibition being stronger towards EGF.
      Pygeum africanum inhibited the proliferation induced by TPA or PDBu in a
      concentration-dependent manner with IC50 values of 12.4 and 8.1 micrograms./ml.
      respectively. The antiproliferative effects of Pa were not ascribed to
      cytotoxicity. These results show that Pygeum africanum is a potent inhibitor of
      rat prostatic fibroblast proliferation in response to direct activators of
      protein kinase C, the defined growth factors bFGF, EGF and IGF-I, and the complex
      mixture of mitogens in serum depending on the concentration used. PKC activation
      appears to be an important growth factor-mediated signal transduction for this
      agent. These data suggest that therapeutic effect of Pygeum africanum may be due
      at least in part to the inhibition of growth factors responsible for the
      prostatic overgrowth in man.

PMID- 9146676
TI  - Growth factors in bladder wound healing.
AB  - INTRODUCTION: Surgical and traumatic injuries to the bladder initiate a complex
      series of biological processes that result in wound healing. This process
      involves cellular proliferation, migration and differentiation; removal of
      damaged tissue; and production of extracellular matrix all of which may be
      controlled by growth factors. In skin, keratinocyte growth factor (KGF) is
      induced following incisional injury. We hypothesize that in bladder wound healing
      KGF and other growth factors are induced to modulate tissue repair. METHODS: We
      have created a model of surgical bladder injury in the rodent. At 12, 24 and 48
      hrs and 5 and 7 days after injury, the bladder was bisected and total RNA
      extracted from the anterior or wounded half and posterior or non-wounded half.
      Histological analysis of the bladder wound was performed with Mason's Trichrome
      and immunohistochemistry against smooth muscle alpha actin. RNase protection
      assays were performed to examine the expression of KGF, transforming growth
      factor (TGF)alpha and TGF beta 2 and 3 as well as the receptors for KGF and
      epidermal growth factor (EGF). Lastly, the effects of the exogenous
      administration of KGF on the bladder was tested on neonatal mice by daily
      injections of 5 micrograms KGF per gram body weight for 5 days. RESULTS: At 12
      hours after injury KGF mRNA expression in the anterior wounded bladder half and
      posterior non-wounded bladder half was 8 and 6 times higher respectively,
      compared to unoperated control bladders. A similar response was seen for TGF
      alpha, where the 12 hour mRNA expression was 4.5 times higher in the anterior
      wounded bladder half and 3.5 times higher in the posterior non-wounded bladder
      half compared to unoperated control bladders. The nadir mRNA expression for both
      KGF and TGF alpha occurred at 7 days after bladder injury and was the same as in
      unoperated control bladders. EGFR mRNA expression was approximately 2 times
      higher in both the anterior wounded and posterior non-wounded bladder halves
      compared to the nadir levels which occurred at 24 hours after injury. TGF beta 2
      and beta 3 mRNA levels did not significantly change in either the anterior
      wounded or posterior non-wounded bladder halves. Exogenous KGF stimulation
      resulted in a marked urothelial proliferation when compared to age matched
      control animals. CONCLUSION: During the early phases of bladder wound healing (12
      24 hours post injury), mRNA for KGF and TGF alpha increased, whereas TGF beta 2
      and beta 3 and the KGFR and EGFR remain unchanged. Additionally, exogenous KGF
      has a direct effect on urothelial proliferation. KGF and TGF alpha warrant
      further study as potential mediators of bladder wound healing.

PMID- 9146677
TI  - Immunostimulatory therapy with anti-CD3 monoclonal antibodies and recombinant
      interleukin-2: heightened in vivo expression of mRNA encoding cytotoxic attack
      molecules and immunoregulatory cytokines and regression of murine renal cell
      carcinoma.
AB  - The response rate to IL-2 immunotherapy, currently used in the treatment of
      metastatic renal cell cancer, is limited. Based on our earlier demonstration that
      a combined regimen of monoclonal antibodies directed at the T cell surface
      protein CD3 (anti-CD3 mAbs) and IL-2 is synergistic in constraining tumor
      progression in a murine fibrosarcoma hepatic metastasis model, we have explored
      the efficacy of an anti-CD3 mAbs plus IL-2 regimen in a murine renal cell cancer
      model. Our studies demonstrate that a regimen of anti-CD3 mAbs plus IL-2 is
      superior to treatment with anti-CD3 mAbs alone or IL-2 alone in reducing the
      number of pulmonary metastases and in prolonging survival. Moreover, the
      efficacious regimen is associated with heightened intrapulmonary expression of
      mRNA encoding cytotoxic attack molecules (perforin, granzyme B) and
      immunoregulatory cytokines (IL-4, IL-10 and IFN- gamma).

PMID- 9146678
TI  - The role of pubococcygeus muscle in urinary continence in the male rat.
AB  - The role of the male rat pubococcygeus muscle (Pcm) in the micturition reflex was
      analyzed. Anatomical features of Pcm, electrical stimulation of its nerve,
      electrical recording and stimulation of the muscle and cystometrograms were
      carried out. Results showed that Pcm has fibers attached to the ventrolateral
      part of the external urethral sphincter, and that its activity contributes to
      hold the tail in the midline. Pcm shows activity during fluid expulsion in
      cystometrograms and spontaneous micturitions. This activity produced reflex
      inhibition of detrusor contraction and was not the cause of intravesical high
      frequency oscillations. Thus, it is proposed that Pcm activity produces the
      discharge of its afferents which in turn activates a spinal reflex to promote
      continence.

PMID- 9146679
TI  - Madame Curie and Mayo.

PMID- 9146680
TI  - Effects of a medical intensivist on patient care in a community teaching
      hospital.
AB  - OBJECTIVE: To determine the effect of adding a trained intensivist on patient
      care and educational outcomes in a community teaching hospital. MATERIAL AND
      METHODS: We retrospectively reviewed outcomes for patients admitted to the
      medical intensive-care unit (MICU) of a 270-bed community teaching hospital
      between July 1992 and June 1994. Mortality rates and durations of stay were
      determined for the year before (BD, 1992 through 1993) and the first year after
      (AD, 1993 through 1994) introduction of a full-time director of critical care.
      Performance of resident trainees on a standardized critical-care examination was
      measured for the same periods. RESULTS: Overall, 459 patients in the BD period
      were compared with 471 patients in the AD period. The mix of cases and severity
      of illness (acute physiology and chronic health evaluation or APACHE II scores)
      on admission were similar for the BD and AD periods. MICU mortality decreased
      from 20.9% during the BD to 14.9% during the AD period (P = 0.02), and in
      hospital mortality decreased from 34.0% to 24.6% (P = 0.002). Disease-specific
      mortalities were lower during the AD period for most categories of illness.
      Detailed analysis of a subgroup of patients (those with pneumonia) demonstrated
      no differences in distribution of patients by gender, race, or acuity of illness
      (APACHE II scores). The mortality rate due to pneumonia decreased from 46% during
      the BD period to 31% during the AD period. This decrease was consistent across
      categories of APACHE II scores. From BD to AD periods, mean durations of total
      hospital stay decreased from 22.6 +/- 1.4 days to 17.7 +/- 1.0 days, and mean
      MICU stay decreased from 5.0 +/- 0.3 days to 3.9 +/- 0.3 days (P < 0.05).
      Critical-care in-service examination scores for 22 residents increased from 53.8
      +/- 1.7% to 67.5 +/- 2.2% (P < 0.01), and AD scores were significantly higher
      than BD scores for residents at similar levels of training. CONCLUSION: Addition
      of a medical intensivist was temporally associated with improved clinical and
      educational outcomes in our community teaching hospital.

PMID- 9146682
TI  - Effect of infarct-related artery patency and late potentials on late mortality
      after acute myocardial infarction.
AB  - OBJECTIVE: To assess the effect of patency of the infarct-related artery and the
      presence of late potentials on late cardiac mortality after myocardial
      infarction. MATERIAL AND METHODS: We studied the influence of the infarct-related
      artery patency and the presence of late potentials during signal-averaged
      electrocardiography on late mortality in 124 survivors of acute myocardial
      infarction. In addition, we assessed predictive factors of cardiac mortality by
      univariate and multivariate statistical analysis. RESULTS: A study group of 98
      men and 26 women (mean age, 59 years) who were survivors of acute myocardial
      infarction underwent follow-up for a mean of 3.6 +/- 1.0 years. Immediate
      reperfusion therapy (thrombolysis or direct angioplasty) was accomplished in 71
      patients (57%). During follow-up, 13 cardiac-associated deaths occurred. Infarct
      related artery patency was strongly associated with improved survival, but the
      presence of late potentials did not correlate with increased mortality, even
      among patients with impaired left ventricular function. Univariate and
      multivariate analyses identified occluded infarct-related arteries, prior
      myocardial infarction, reduced left ventricular ejection fraction, and advanced
      age, but not late potentials, as predictors of increased late cardiac mortality.
      CONCLUSION: These data suggest that coronary angiography may, but signal-averaged
      electrocardiography may not, identify patients with increased late risk of
      cardiac-related death after myocardial infarction. The low mortality among
      patients who have undergone successful reperfusion therapy may reduce the ability
      of noninvasive tests to distinguish between high- and low-risk patients.

PMID- 9146681
TI  - Syndrome of orthostatic headaches and diffuse pachymeningeal gadolinium
      enhancement.
AB  - OBJECTIVE: To characterize clinical and imaging features, biopsy findings,
      etiologic factors, and outcome in the syndrome of intracranial hypotension,
      headaches, and diffuse pachymeningeal gadolinium enhancement on magnetic
      resonance imaging (MRI). MATERIAL AND METHODS: We describe our experience with 26
      consecutive patients with orthostatic headaches and diffuse pachymeningeal
      gadolinium enhancement, for all of whom clinical, imaging, and follow-up data
      were available. For 10 patients who had undergone meningeal biopsy, slide
      material was also reviewed. RESULTS: The 15 men and 11 women ranged from 24 to 76
      years of age. All 26 patients had postural headaches; in 22 patients, the
      headaches were completely alleviated by recumbency. Nausea or emesis, neck pain,
      horizontal diplopia, changes in hearing, photophobia, upper limb pains or
      paresthesias, visual blurring, or dysgeusia was noted in some of the patients.
      Cardinal MRI features were diffuse pachymeningeal gadolinium enhancement (100%),
      subdural collections of fluid (69%), and evidence of descent of the brain (62%)
      that sometimes resembled type I Chiari malformation. Cerebrospinal fluid (CSF)
      opening pressures were 40 mm or less in only 46%. In three patients, CSF
      pressures were consistently no less than 90 and as high as 130 mm of water. A
      variable pleocytosis of 5 or more cells/mm3 was noted in 15 patients (more than
      40 cells/mm3 in 4 patients). A variable increase in CSF protein was noted in at
      least one spinal tap in 23 patients. Six patients had overdraining CSF shunts;
      CSF leak was documented in another 11 patients. Shunt revision or ligation and
      surgical correction of the leak led to a resolution of the clinical and MRI
      abnormalities in all cases thus treated. Improvement occurred with epidural blood
      patch in four patients. Three of the 12 patients treated supportively have
      remained symptomatic. Histologically, a thin subdural zone of fibroblasts and
      thin-walled vessels was noted in an amorphous matrix. Two patients with prolonged
      symptoms had a more pronounced proliferative reaction. CONCLUSION: The syndrome
      of low-pressure headaches and pachymeningeal gadolinium enhancement is being
      recognized with increasing frequency. The source of the CSF leak can be
      demonstrated in many patients. Meningeal abnormalities are likely attributable to
      decreased CSF volume and hydrostatic CSF pressure changes. The prognosis is
      typically good.

PMID- 9146683
TI  - Thomas Huckle Weller and the successful culture of poliovirus.

PMID- 9146684
TI  - Increased lymphoscintigraphic flow pattern in the lower extremity under
      evaluation for lymphedema.
AB  - OBJECTIVE: To analyze the clinical and scintigraphic features in four
      postoperative patients with lower limb edema. DESIGN: Four case reports are
      presented, and causes of increased lymphatic flow are discussed. MATERIAL AND
      METHODS: Filtered 99mTc-sulfur colloid (0.1 mL; 20 MBq) was administered by
      subcutaneous injection into the second web space of each foot. Sequential local
      (inguinal) and whole-body imaging was performed periodically up to 24 hours after
      the injections. The patients were three women who were 40, 51, and 86 years of
      age and an 81-year-old man. RESULTS: Each patient had unilateral lower extremity
      swelling and had recently undergone an ipsilateral lower limb operation. One
      female patient had previously undergone proximal femoral vein ligation, and
      another female patient had venous insufficiency demonstrated by Doppler
      ultrasonography. The male patient had a history of severe arterial insufficiency,
      and the remaining female patient had no venous or arterial abnormalities. On
      lymphoscintigraphy, all patients showed increased lymphatic flow in the edematous
      lower limb. Only the male patient also demonstrated abnormal dermal backflow
      pattern. CONCLUSION: Increased lymphatic flow most likely is a normal response to
      lower limb edema in the presence of normal peripheral lymphatic structures. In
      the four described cases, a recent lower limb surgical procedure may have
      resulted in disturbance of normal proximal lymphatic channels. The role of
      sympathetic innervation of the peripheral lymphatic system is a potential factor
      determining lymphatic response to trauma or surgical intervention. Increased flow
      on lymphoscintigraphy may not necessarily represent normal flow, especially if
      other scintigraphic features of abnormal lymphatic function-such as dermal
      backflow pattern-are present.

PMID- 9146685
TI  - Genetic testing in medullary thyroid carcinoma syndromes: mutation types and
      clinical significance.
AB  - OBJECTIVE: To determine the types of mutations and the clinical significance of a
      specific genotype in familial medullary thyroid carcinoma (MTC) syndromes.
      DESIGN: We retrospectively and prospectively studied patients with MTC at a
      tertiary referral center. MATERIAL AND METHODS: The study cohort consisted of 348
      affected patients and at-risk family members of MTC kindreds, including 33
      multiple endocrine neoplasia type IIA (MEN IIA) kindreds with 165 members, 13
      familial MTC alone (FMTC) kindreds (at least 4 affected members with MTC per
      kindred, without evidence of pheochromocytoma and hyperparathyroidism) with 108
      members, 15 "other hereditary MTC" kindreds (2 or 3 affected members) with 42
      members, and 33 individuals with sporadic MTC. An additional 53 subjects from the
      aforementioned MEN IIA kindreds who were clinically affected but not genetically
      tested were also included in an analysis of the relationship between genotype and
      phenotype. The presence of germline mutations in the RET proto-oncogene was
      studied by DNA sequence analysis of exons 10, 11, and 13. RESULTS: Germline RET
      mutations in exons 10 and 11 were identified in 32 of 33 MEN IIA kindreds (97%),
      10 of 13 FMTC kindreds (77%), and 10 of 15 "other hereditary MTC" kindreds (67%).
      No mutations were identified in exon 13. No patient with sporadic MTC had a
      germline mutation. In MEN IIA, codon 634 was affected in 73% of the kindreds,
      whereas in FMTC, the main affected codon was codon 618 (54%). In MEN IIA,
      patients with codon 634 mutations had a higher risk of having C-cell disease,
      pheochromocytoma, and hyperparathyroidism than did those with other mutations (P
      < 0.05, P < 0.001, and P < 0.01, respectively). CONCLUSION: RET analysis is a
      reliable, practical, and cost-effective test in the screening of at-risk family
      members of MEN IIA and FMTC kindreds. In addition, RET analysis may be helpful in
      the follow-up of gene carriers and for the early detection of pheochromocytoma
      and hyperparathyroidism in patients with codon 634 mutations.

PMID- 9146686
TI  - Giant fusiform aneurysm presenting as fatal basilar artery occlusion.
AB  - Fusiform aneurysms are often asymptomatic, and therefore their actual incidence
      is unknown. Ischemic stroke has been linked to dislodgment of small thrombi
      formed inside the aneurysm but is uncommon. This article describes two patients
      with rapidly fatal infarction in the entire pons, both cerebellar hemispheres,
      thalamus, and occipital lobes, findings consistent with occlusion of the
      vertebrobasilar artery complex. In both patients, autopsies revealed a giant
      fusiform aneurysm of the basilar artery.

PMID- 9146687
TI  - Vitamin D metabolite-mediated hypercalcemia in Wegener's granulomatosis.
AB  - Hypercalcemia may occur during the course of various granuloma-forming diseases.
      Herein we describe a patient who had symptomatic hypercalcemia as a prominent
      sign of Wegener's granulomatosis. We observed a direct correlation between the
      serum levels of 1,25-dihydroxyvitamin D [1,25(OH)2D] and both the serum and the
      urinary calcium levels. Administration of prednisone and cyclophosphamide led to
      a substantial decrease in the levels of calcium and serum 1,25(OH)2D, but the
      serum levels of 25-hydroxyvitamin D remained unchanged. Two months after
      admission of the patient, the levels of calcium and 1,25(OH)2D increased; after
      we increased the dose of cyclophosphamide, these levels decreased (the dose of
      corticosteroids was not changed). We suggest that the excessive synthesis of
      1,25(OH)2D was inhibited by a direct or indirect action not only of prednisone
      but also of cyclophosphamide on the 1 alpha-hydroxylation of 25-hydroxyvitamin D
      in the activated macrophage of Wegener granulomas. Furthermore, in view of this
      case and two other recently reported cases, we believe that Wegener's
      granulomatosis must be definitively added to the list of granulomatous diseases
      that are responsible for 1,25(OH)2D-mediated hypercalcemia.

PMID- 9146688
TI  - Chronic granulocytic leukemia: recent information on pathogenesis, diagnosis, and
      disease monitoring.
AB  - Current evidence strongly implicates the chromosome translocation
      t(9;22)(q34;q11.2) as the cause of chronic granulocytic leukemia. Therefore,
      identification of this genetic abnormality through either cytogenetic or
      molecular methods has become a requirement for diagnosis. Intense investigation
      of the mechanism by which t(9;22) transforms normal hematopoietic progenitors
      into malignant cells is ongoing. Recent advances in molecular diagnostic methods
      have allowed refined qualitative and quantitative methods of detecting t(9;22),
      which are useful for monitoring response status and detecting minimal residual
      disease. The current understanding of the pathogenesis of chronic granulocytic
      leukemia and the application of new diagnostic methods are discussed.

PMID- 9146689
TI  - Congestive heart failure in elderly patients.
AB  - The prevalence of congestive heart failure (CHF) is increasing. Most patients
      with CHF are elderly, and CHF is the most common dismissal diagnosis in elderly
      hospitalized patients. As many as 50% of elderly patients with heart failure may
      have normal systolic function and isolated diastolic heart failure. Assessment
      and management of elderly patients are complicated by comorbidities, increased
      susceptibility to side effects, and concerns about the appropriate use of costly
      and invasive procedures. The basics of the approach to the evaluation and
      management of heart failure in elderly patients are reviewed.

PMID- 9146690
TI  - Suntanning: differences in perceptions throughout history.
AB  - In ancient times, the sun was venerated as a source of life in some cultures.
      Scientifically, the relationship between vitamin D and sunlight and the
      deficiency of vitamin D in patients with rickets were ultimately discovered. In
      1903, Niels Finsen was awarded the Nobel Prize in medicine or physiology for his
      "Finsen light therapy" for infectious diseases, especially lupus vulgaris. In the
      1930s and 1940s, the medical profession promoted sunbathing as beneficial for
      children. From these bases, the popularity of suntanning emerged, promoted by the
      availability of more leisure time and, eventually, the development of sunlamps
      and commercial tanning salons. Although the precise role of ultraviolet light in
      the pathogenesis of melanoma is uncertain, a melanoma epidemic began to be
      noticed in the 1970s. During the past 15 years, campaigns have attempted to
      educate the public about the potential dangers of suntanning and exposure to
      ultraviolet light. Whether the melanoma epidemic can be reversed remains to be
      seen.

PMID- 9146691
TI  - Genetics of cutaneous melanoma and nevi.
AB  - To provide a state-of-the-art summary of currently available data about the
      genetics of cutaneous melanoma and nevi, we reviewed the pertinent literature and
      outlined the important findings on genetic analyses. Although the first English
      language report of melanoma in 1820 contained a description of a melanoma-prone
      family, seminal studies by investigators at the National Cancer Institute and the
      University of Pennsylvania identified dysplastic nevi (DN) as an important
      melanoma precursor, suggested an autosomal dominant mode of inheritance for both
      melanoma and DN, and proposed that a melanoma-susceptibility gene (CMM1) was
      located on chromosome 1p36. This gene assignment has not yet been confirmed by
      independent investigators. A second melanoma gene, designated CMM2, has been
      mapped to chromosome 9p21. This gene assignment has been confirmed independently,
      and the cell cycle regulator p16INK4a has been proposed as a candidate gene;
      germline mutations in this gene have been identified in about half of melanoma
      prone families. Germline mutations in the cyclin-dependent kinase gene CDK4
      (chromosome 12q14) have recently been described in two melanoma kindreds; this
      finding likely represents a third melanoma gene. A heritable determinant for
      total nevus number has been suggested, as has the presence of a major gene
      responsible for total nevus density in melanoma-prone families. An autosomal
      dominant mode of inheritance for DN has been proposed, and evidence suggests that
      DN may be a pleiotropic manifestation of the 1p36 familial melanoma gene. Several
      studies have shown a surprisingly high prevalence of DN on the skin of family
      members of probands with DN. In light of the extensive evidence documenting that
      persons with DN (both sporadic and familial) have an increased prospective risk
      for melanoma, these family studies suggest that relatives of persons with DN
      should be examined for DN and for melanoma. Overall, genetic determinants have a
      major role in the pathogenesis of normal nevi, DN, and melanoma. Elucidating the
      molecular basis of these genetic events promises to enhance melanoma risk
      reduction strategies and thereby reduce melanoma-associated mortality.

PMID- 9146692
TI  - The life of a skin cancer.
AB  - The mechanisms of carcinogenesis and metastasis are becoming better elucidated.
      The recent literature pertaining to the current understanding of the mechanisms
      of carcinogenesis and metastasis was reviewed, and some of the basic information
      that is known about these processes and how they relate to the development of
      cutaneous cancers is presented in this article. The development of a skin cancer
      consists of a three-step process of carcinogenesis-initiation, promotion, and
      progression. When metastasis occurs, a six-step process of complex cellular
      adaptations enables the tumor cell to metastasize and proliferate successfully.
      The mechanisms of carcinogenesis and metastasis are pertinent not only to
      dermatologists and physicians who treat skin cancer but also to any physician who
      must manage human malignant tumors. Therefore, a general background of
      information on this subject is an important aspect of medical knowledge for most
      physicians.

PMID- 9146693
TI  - 26-year-old man with hyperpigmentation of skin and lower extremity spasticity.

PMID- 9146694
TI  - Streamlining critical care: responsibilities and cost-effectiveness in intensive
      care unit organization.

PMID- 9146695
TI  - Serum-ascitic fluid albumin gradient, portal hypertension, and ascites.

PMID- 9146696
TI  - Pilot findings of a percutaneous transluminal coronary angioplasty-restenosis
      prone prevention program.

PMID- 9146697
TI  - Telomeres, telomerase and chromosome stability.
AB  - Telomeres in most species consist of repeat units of a small number of
      nucleotides that together with secondary structures and associated proteins
      stabilize the linear chromosomal DNA molecule. Chromosomes lose a small amount of
      telomeric DNA after each cell replication. It has been proposed that when
      telomeres shorten below a critical length, a DNA damage response pathway is
      activated and induces cell cycle arrest. In cells such as stem cells that
      maintain a proliferative capacity, telomere length is maintained by the reverse
      transcriptase, telomerase. In addition, telomerase activity is present in 90% of
      primary human tumors, suggesting a role for telomerase in providing a
      proliferative capacity to cells, which is a requirement in progression to
      malignancy. Telomerase activity can be involved in chromosome healing, although
      telomerase-independent processes also appear to be capable of capping broken
      chromosome ends. This review describes the structure and maintenance of
      telomeres, the importance of a critical telomere length to cell proliferation and
      the telomeric status of broken chromosome ends produced during development or by
      spontaneous or induced DNA damages.

PMID- 9146698
TI  - The scid defect results in much slower repair of DNA double-strand breaks but not
      high levels of residual breaks.
AB  - Severe combined immune deficiency (scid) mice fail to produce mature B and T
      cells and are sensitive to ionizing radiation. They contain a mutation in the 460
      kDa catalytic subunit of the DNA-dependent protein kinase that is involved in
      both V(D)J rejoining and DNA double-strand break (DSB) repair. The kinetics of
      DSB rejoining was quantified in both scid cells and the parental C.B-17 cells
      after three different doses of X irradiation: 3, 7.5 and 10 Gy. Repair of DNA
      DSBs was determined using pulsed-field gel electrophoresis, Southern
      hybridization and phosphor image analysis. After X irradiation, the cells were
      allowed to repair at 37 degrees C for up to 1 h or up to 24 h. The most profound
      difference between the two cell lines was the greatly reduced rate of the slow
      component of DSB repair in scid cells. C.B-17 cells repaired most of the damage
      within 1 h, whereas scid cells required 4 to 6 h to reach a similar level after
      the same dose. No residual or unrepairable DSBs were detected in either cell line
      24 h after doses as high as 10 Gy. The scid cells subjected to two doses of 1.5
      Gy separated by increasing amounts of time showed no ability to repair sublethal
      damage between doses, whereas C.B-17 cells receiving two doses of 3.75 Gy
      separated by increasing periods did show increased levels of survival. These
      results indicate that scid cells can repair radiation-induced DNA DSBs, although
      at a reduced rate, but they lack the ability to undergo repair of sublethal
      damage.

PMID- 9146699
TI  - Cells at intermediate oxygen levels can be more important than the "hypoxic
      fraction" in determining tumor response to fractionated radiotherapy.
AB  - The presence of hypoxic cells in human tumors is thought to be one of the
      principal reasons for the failure of radiation therapy. Intensive laboratory and
      clinical efforts to overcome tumor hypoxia have focused on oxygenating,
      radiosensitizing or killing the maximally radioresistant fraction of tumor cells.
      This "hypoxic fraction" dominates the single-dose radiation response,
      irrespective of the oxygenation status of the remainder of the tumor cell
      population. However, at doses that are typical of those delivered in a daily
      radiotherapy protocol, we show that the tumor response is highly dependent upon
      the cells at oxygen levels intermediate between fully oxygenated and hypoxic (0.5
      20 mm Hg). For most tumors, these cells are more important than the
      radiobiologically hypoxic cells in determining treatment outcome after 30
      fractions of 2 Gy. We also show that under conditions of diffusion-limited
      hypoxia, the impact of full reoxygenation between fractions is much smaller than
      previously realized. Together, the results imply that tumor hypoxia plays a more
      significant role in determining the outcome of fractionated radiotherapy than
      previous measurements and assumptions of hypoxic fractions have indicated.
      Therefore, the concept of a hypoxic fraction in human tumors is less meaningful
      when pertaining to a fractionated radiotherapy regimen, and should not be
      expected to be useful for predicting tumor responses in the clinic. This implies
      the need to characterize tumor oxygenation in a manner that reflects the true
      oxygenation status of all the tumor cells, not just the ones most refractory to
      the effects of ionizing radiation. Furthermore, effective therapeutic agents must
      have the ability to specifically sensitize or kill those cells at intermediate
      levels of oxygen in addition to the radiobiologically hypoxic cells.

PMID- 9146700
TI  - A theoretical study of light fractionation and dose-rate effects in photodynamic
      therapy.
AB  - The efficacy of photodynamic therapy is dependent upon the optical dose rate or
      upon the fractionation schedule on the light. These effects are thought to be
      limited by the time required for oxygen diffusion from the capillaries, since
      this therapy can consume oxygen faster than it can be supplied to tissues distant
      from the blood vessels. Oxygen diffusion and consumption by metabolic and
      photochemical mechanisms have been modeled here to compare theoretical
      predictions with experimental results of varying light fractionations and
      delivered dose rates. The mathematics of the problem have been described in the
      literature, and the present study extends these calculations to allow a more
      direct and quantitative comparison with fractionation experiments, using both
      analytical and numerical arguments. The optimum fraction time was found to depend
      only on the intercapillary spacing and not on the intensity of irradiation or the
      concentration of photosensitizer. The calculations indicate that experimentally
      observed optimum fractionation times of 30 and 60 s correspond to a distance from
      capillary to cell of approximately 1 mm. These results suggest that the
      fractionated light irradiation experiments need careful interpretation, and some
      possible reasons for longer optimum fractionation times are discussed.

PMID- 9146701
TI  - The effects of lattice water on free radical yields in X-irradiated crystalline
      pyrimidines and purines: a low-temperature electron paramagnetic resonance
      investigation.
AB  - The hydration layer of DNA increases the target size of DNA with respect to the
      formation of direct-type damage by ionizing radiation. The mechanisms that give
      rise to this increase are being investigated by EPR spectroscopy. To determine
      these mechanisms, it is necessary to distinguish between the change in sample
      mass and changes in packing/conformation brought about by the change in the level
      of hydration. Certain model compounds that crystallize as hydrates provide a
      system where the effects of mass and packing can be discerned. Three such hydrate
      crystals were used in this work: barbituric acid dihydrate (BA:2H2O), inosine
      dihydrate (IR:2H2O) and thymine monohydrate (T:H2O). The free radical yields (+/
      25%) in the native crystals at 7-11 K are 0.08, 0.03 and 0.02, respectively.
      Removal of the lattice water leaves behind an ordered lattice and results in free
      radical yields of 0.08, 0.03 and < 0.004, respectively. Thus removal of the
      lattice water does not affect the free radical yield in BA:2H2O or IR:2H2O but
      decreases the free radical yield in T:H2O by an order of magnitude. Based on
      these observations and the known crystal packing, we conclude that the hydrogen
      bonding network is a major factor in determining the distribution and yield of
      trapped free radicals. We ascribe this to the importance of proton transfer
      processes which act to reduce the probability of radical combination. Consistent
      with this conclusion are the types of free radicals trapped in these crystalline
      materials before and after dehydration. From these results, we argue that a major
      determinant of free radical yields in solidstate samples of DNA constituents is
      molecular packing. In addition, the absence of HO. radicals trapped in single
      crystals of BA:2H2O provides an upper limit for the yield of trapped HO. of less
      than 10(-4) mumol/J. This supports the thesis that at < 77 K direct ionization of
      those waters associated directly with a pyrimidine or purine results in hole
      transfer to that molecule. Hydroxyl radical formation on a water adjacent to a
      DNA base is predicted to be negligible.

PMID- 9146702
TI  - Subdenaturing (pH 11.1) filter elution: more sensitive quantification of DNA
      double-strand breaks.
AB  - The apparent biological significance of DNA double-strand breaks (DSBs) has
      stimulated considerable effort toward quantification of this lesion. The neutral
      (or nondenaturing) filter elution assay at pH 7.2 or 9.6 has long been a standard
      method for the measurement of double-strand breakage and rejoining in eukaryotic
      cells, with a threshold dose for detection of DSBs of 5-10 Gy. Agarose gel
      electrophoresis, either pulsed- or constant-field, can detect DSBs induced by as
      little as 1 Gy of ionizing radiation, but electrophoresis assays may have
      inherent problems in measurement of break rejoining, and may be more susceptible
      than elution to factors other than break frequency, such as cell cycle stage or
      bromodeoxyuridine substitution. We report here that filter elution performed at
      pH 11.1 can detect DSBs produced by only 1 Gy of ionizing radiation, but is
      insensitive to the single-strand breaks that are formed when cells are exposed to
      hydrogen peroxide. Double-strand breaks produced in permeabilized cells by the
      restriction endonuclease HaeIII were used to demonstrate that the increase in the
      pH of the eluting solution from 9.6 to 11.1, although increasing assay
      sensitivity by a factor of five, converts few additional alkali-labile sites to
      DSBs. Thus validated, the pH 11.1 filter elution assay was applied to a low-dose
      measurement of induction and rejoining of DSBs in 9L cells.

PMID- 9146703
TI  - Unexpected rates of chromosomal instabilities and alterations of hormone levels
      in Namibian uranium miners.
AB  - A common problem in determining the health consequences of radiation exposure is
      factoring out other carcinogenic influences. The conditions in Namibia provide a
      test case for distinguishing the effects of long-term low-dose exposure to
      uranium from the other environmental factors because of good air quality and the
      lack of other industries with negative health effects. Present records indicate a
      much higher prevalence of cancer among male workers in the open-pit uranium mine
      in Namibia compared with the general population. The objective of the present
      study was to determine whether long-term exposure to low doses of uranium
      increases the risk of a biological radiation damage which would lead to malignant
      diseases and to derive a dose-response model for these miners. To investigate
      this risk, we measured uranium excretion in urine, neutrophil counts and the
      serum level of FSH, LH and testosterone and analyzed chromosome aberrations in
      whole blood cells using fluorescence in situ hybridization. A representative
      cohort of 75 non-smoking, HIV-negative miners was compared to a control group of
      31 individuals with no occupational history in mining. A sixfold increase in
      uranium excretion among the miners compared to the controls was recorded (P <
      0.001). Furthermore, we determined a significant reduction in testosterone levels
      (P < 0.008) and neutrophil count (P < 0.004) in miners compared to the unexposed
      controls. A threefold increase in chromosome aberrations in the miners compared
      to the nonexposed controls was recorded (P < 0.0001). Most remarkably, cells with
      multiple aberrations such as "rogue" cells were observed for the first time in
      miners; these cells had previously been found only after short-term high-dose
      radiation exposure, e.g. from the Hiroshima atomic bomb or the Chernobyl
      accident. We conclude that the miners exposed to uranium are at an increased risk
      to acquire various degrees of genetic damage, and that the damage may be
      associated with an increased risk for malignant transformation. As expected, the
      chronic radiation injury of the hematopoietic system resulted in low neutrophil
      counts. Also, low hormone levels probably reflect damage to the gonadal endocrine
      system.

PMID- 9146704
TI  - Hyaluronan in radiation-induced lung disease in the rat.
AB  - We have used a previously described model of bilateral radiation-induced lung
      disease in the rat (Ward et al., Radiat. Res., 136, 15-21, 1993) to study the
      role of hyaluronan in this process. Hyaluronan was measured in the
      bronchoalveolar lavage fluid, serum and lung tissue of rats after gamma
      irradiation or sham irradiation. Four weeks after irradiation, during peak
      alveolitis (12-fold increase in protein in the lavage, 7-fold increase in lavaged
      cells) hyaluronan was elevated 5.5-fold in serum and 1.5-fold in the
      bronchoalveolar lavage fluid. Histochemical staining demonstrated hyaluronan was
      in the intra-alveolar edema fluid but was not increased in the alveolar walls;
      hyaluronan, measured by high-performance liquid chromatography, also was not
      elevated in lavaged lung tissue. Hyaluronan was not increased in bron-choalveolar
      lavage fluid, serum or lung tissue during pulmonary edema (2 weeks) or fibrosis
      (6 to 20 weeks). The administration of methylprednisolone significantly decreased
      the alveolitis, including the increase in hyaluronan in the alveolar space and
      serum, but did not suppress fibrosis. It appears that hyaluronan is a marker of
      inflammation and cannot be used as a serum marker to predict the onset of
      radiation pneumonitis. Furthermore, an increase in interstitial hyaluronan does
      not appear to be a necessary precursor in the evolution of radiation fibrosis.

PMID- 9146705
TI  - Alteration of transcriptional and post-transcriptional expression of gamma
      glutamylcysteine synthetase by diethyl maleate.
AB  - Gamma-glutamylcysteine synthetase (gamma-GCS), also known as glutamate-cysteine
      ligase (EC 6.3.2.2), is the rate-limiting enzyme in the synthesis of glutathione
      (GSH). The gene GLCLC encodes the catalytic subunit while GLCLR encodes the
      regulatory subunit. Although it has been shown that GLCLC can respond to a
      variety of stresses by increased transcription, it is not known whether a similar
      response occurs for GLCLR. Nor is it known whether post-transcriptional
      regulation of either gene product is altered during stress. The present
      investigation was undertaken to explore transcriptional and post-transcriptional
      regulation of GLCLC and GLCLR gene products when HepG2 cells were challenged with
      the radiation sensitizer diethyl maleate (DEM). Expression of steady-state GLCLC
      and GLCLR mRNA was enhanced 5-20-fold after DEM challenge. Nuclear run-off assays
      were performed on unstressed and stressed cells to determine whether the
      increased expression of GLCLC and GLCLR mRNA was due to altered transcriptional
      activity of these genes. The DEM treatment increased the transcription rates of
      both genes 2-5-fold. In unstressed HepG2 cells, the half-life of GLCLC mRNA
      transcripts was approximately 4 h. In contrast, the half-life of GLCLR
      transcripts was approximately 8 h. In cells treated with DEM, the half-lives of
      all transcripts were increased, indicating that message stabilization contributed
      to the increased expression of gene products. Finally, a PEST algorithm has
      identified a PEST (proline, glutamate, serine, threonine) motif within the
      catalytic subunit of gamma-GCS, suggesting that this subunit might exhibit
      conditional proteolytic regulation. These results imply that regulation of the
      products of the GLCLC and GLCLR genes may be altered at multiple levels during
      exposure to stress.

PMID- 9146707
TI  - Enhancement of radiation-induced hepatic microsomal epoxide hydrolase gene
      expression by oltipraz in rats.
AB  - The effects of radiation exposure in conjunction with oltipraz, a chemopreventive
      agent, on the expression of the gene encoding hepatic microsomal epoxide
      hydrolase (mEH) were examined in rats. Rats exposed to a single dose of 3 Gy
      gamma rays exhibited timerelated changes in the hepatic mEH mRNA level. Whereas
      the mEH mRNA level was transiently decreased at 3 and 8 h after irradiation, the
      mRNA levels were increased 3- to 4-fold at 15 to 48 h postirradiation, returning
      to the level in untreated animals at 72 h. Treatment of rats with oltipraz
      resulted in 1- to 19-fold increases in hepatic mEH mRNA levels 24 h post
      treatment at doses of 5-200 mg/kg. Although treatment with oltipraz at a dose of
      30 mg/kg affected the mEH mRNA level minimally (i.e. approximately 2-fold), 3 Gy
      whole-body irradiation along with oltipraz treatment resulted in a 9-fold
      increase in the mEH mRNA level at 24 h post-treatment. Treatment of animals with
      both oltipraz and 3 Gy gamma radiation for 3 consecutive days resulted in a 7
      fold increase in mEH mRNA, showing that the increases in mEH mRNA were enhanced
      by the combination treatment. In rats irradiated with 3 Gy for 5 consecutive
      days, however, the mEH mRNA level failed to increase due to cell injury. Studies
      were further designed to assess the effects of 0.5 Gy ionizing radiation and
      concomitant oltipraz treatment. RNA blot analysis showed that mEH mRNA levels
      failed to be significantly altered at 3, 8, 15, 24 and 48 h after a single dose
      of 0.5 Gy. Nonetheless, exposure of animals to 0.5 Gy daily for 3 to 5
      consecutive days caused a 3-fold elevation in the hepatic mEH mRNA level.
      Furthermore, treatment of animals with both oltipraz (30 mg/kg/day) and 0.5 Gy of
      gamma rays resulted in an enhanced elevation in the mEH mRNA level at 24 h post
      treatment compared to the individual treatment, resulting in a 7-fold relative
      increase. The enhanced expression of hepatic mEH mRNA by 0.5 Gy gamma radiation
      and oltipraz was also observed after treatment for 3 to 5 days (8- to 6-fold
      relative increases). Western immunoblot analyses showed that hepatic microsomes
      produced from the rats treated with 0.5 Gy daily for 3 to 5 days resulted in a
      approximately 2-fold induction of hepatic mEH and that rats exposed to radiation
      in combination with oltipraz showed 3-fold increases in the liver mEH protein.
      Thus the relative increase in mEH mRNA levels was consistent with the expression
      of the protein. These results demonstrate that ionizing radiation causes
      alterations in hepatic mEH gene expression with the induction of the protein and
      that the mEH gene expression is enhanced by oltipraz treatment.

PMID- 9146706
TI  - Dose responses from inhaled monodisperse aerosols of 244Cm2O3 in the lung, liver
      and skeleton of F344 rats and comparison with 239PuO2.
AB  - The purpose of this study was to obtain information on the alpha-particle dose
      response relationship of 244Cm in rats. Rats were exposed briefly by inhalation
      to graded levels of monodisperse aerosols of 244Cm2O3 heat-treated at 1150
      degrees C. The initial lung burden (ILB) of each animal was determined by the use
      of the gamma-ray-emitting radionuclide 243Cm in the aerosols. Seven groups of 84
      day-old F344/Crl rats (a total of 637 males and 645 females) were exposed once to
      244Cm2O3 or sham-exposed to filtered ambient air. Mean ILBs of all rats per group
      ranged from 0.51 +/- 0.17 (+/-SD) to 240 +/- 82 kBq kg-1 body weight. Mean
      lifetime alpha-particle doses to the lungs per group ranged from 0.20 +/- 0.069
      (+/-SD) to 36 +/- 6.5 Gy. After death, each rat was radiographed and necropsied.
      Dose-related increases occurred in incidences of benign and malignant lung
      neoplasms, except for the groups of rats with higher mean ILBs that were examined
      histologically (98 +/- 18 and 240 +/- 77 kBq kg-1 body weight) in which survival
      was markedly decreased. Also, average alpha-particle doses of 0.0014 +/- 0.00058
      (+/-SD) to 0.17 +/- 0.091 Gy and 0.18 +/- 0.007 to 1.6 +/- 1.1 Gy were also
      absorbed by the liver and skeleton, respectively, in the rats in the different
      exposure groups. Primary liver neoplasms occurred in several rats. However, the
      incidence of these lesions was not related to dose. Increased incidences of bone
      neoplasms occurred only in rats receiving higher doses to the skeleton. Excess
      numbers of rats with lung neoplasms per 10(4) Gy to the lung per group ranged
      from 760 +/- 430 (+/- SE) at a mean dose of 0.48 Gy to 84 +/- 16 at a mean dose
      of 37 Gy. Risk factors for the lowest and highest ILB kg-1 body weight groups
      were not considered reliable because of large errors associated with these
      calculations and the life-span shortening in the highest ILB kg-1 group. Inhaled
      244Cm2O3 appeared to be about 50% less effective as a lung carcinogen in rats
      compared to 239PuO2 at similar doses.

PMID- 9146708
TI  - Late effects of X irradiation on regulation of cerebral blood flow after whole
      brain exposure in rats.
AB  - Hemodynamic parameters such as total cerebral blood volume (total CBV), cerebral
      parenchymal blood volume (CBV), cerebral blood flow (CBF) and cerebral blood
      velocity index were measured in rats 6, 12 and 18 months after single exposures
      of brain to 5, 10, 15 and 20 Gy X rays for total CBV, CBF and blood velocity
      index, and only 20 Gy for CBV. Total CBV and blood velocity index were determined
      by a noninvasive blood dilution method using [99mTc]pertechnetate and CBF by
      [131I]iodoantipyrine brain extraction. The CBV was obtained from both parenchymal
      plasma and erythrocyte volumes measured in isolated brain by 125I-labeled serum
      albumin and 51Cr-labeled erythrocytes, respectively. Neither the dose nor the
      time after irradiation influenced total CBV. Nevertheless, CBV decreased slightly
      while CBF decreased strongly at 12 and 18 months after 20 Gy. In contrast, the
      blood velocity index increased progressively at 12 and 18 months after 15 Gy and
      at all times after 20 Gy. According to the coexistence in irradiated brains of a
      remodeling with microvascular occlusions and dilated abnormal vessels, this
      lowered CBF can be explained by the smaller number of open capillaries and a
      "steal phenomenon" through low-resistance channels developed in the parenchymal
      and extraparenchymal vasculatures. Such a "steal phenomenon" is also supported by
      the response of the blood velocity index, which appears to be the earliest
      sensitive index for the detection of hemodynamic changes with respect to time (6
      months) and dose of radiation (15 Gy).

PMID- 9146709
TI  - Lymphomas in E mu-Pim1 transgenic mice exposed to pulsed 900 MHZ electromagnetic
      fields.
AB  - Whether radiofrequency (RF) fields are carcinogenic is controversial;
      epidemiological data have been inconclusive and animal tests limited. The aim of
      the present study was to determine whether long-term exposure to pulse-modulated
      RF fields similar to those used in digital mobile telecommunications would
      increase the incidence of lymphoma in E mu-Pim1 transgenic mice, which are
      moderately predisposed to develop lymphoma spontaneously. One hundred female E mu
      Pim1 mice were sham-exposed and 101 were exposed for two 30-min periods per day
      for up to 18 months to plane-wave fields of 900 MHz with a pulse repetition
      frequency of 217 Hz and a pulse width of 0.6 ms. Incident power densities were
      2.6-13 W/m2 and specific absorption rates were 0.008-4.2 W/kg, averaging 0.13-1.4
      W/kg. Lymphoma risk was found to be significantly higher in the exposed mice than
      in the controls (OR = 2.4. P = 0.006, 95% CI = 1.3-4.5). Follicular lymphomas
      were the major contributor to the increased tumor incidence. Thus long-term
      intermittent exposure to RF fields can enhance the probability that mice carrying
      a lymphomagenic oncogene will develop lymphomas. We suggest that such genetically
      cancer-prone mice provide an experimental system for more detailed assessment of
      dose-response relationships for risk of cancer after RF-field exposure.

PMID- 9146710
TI  - The Estonian study of Chernobyl cleanup workers: I. Design and questionnaire
      data.
AB  - Nearly 2% of the male population of Estonia aged 20-39 years were sent to
      Chernobyl to assist in the cleanup activities after the reactor accident. A
      cohort of 4,833 cleanup workers was assembled based on multiple and independent
      sources of information. Information obtained from 3,704 responses to a detailed
      questionnaire indicated that 63% of the workers were sent to Chernobyl in 1986;
      54% were of Estonian and 35% of Russian ethnicity; 72% were married, and 1,164 of
      their 5,392 children were conceived after the Chernobyl disaster. The workers
      were less educated than their counterparts in the general population of Estonia,
      and only 8.5% had attended university. Based on doses entered in worker records,
      the mean dose was 11 cGy, with only 1.4% over 25 cGy. Nearly 85% of the workers
      were sent as part of military training activities, and more than half spent in
      excess of 3 months in the Chernobyl area. Thirty-six percent of the workers
      reported having worked within the immediate vicinity of the accident site; 11.5%
      worked on the roofs near the damaged reactor, clearing the highly radioactive
      debris. The most commonly performed task was the removal and burial of topsoil
      (55% of the workers). Potassium iodide was given to over 18% of the men. The
      study design also incorporates biological indicators of exposure based on the
      glycophorin A mutational assay of red blood cells and chromosome translocation
      analyses of lymphocytes; record linkage with national cancer registry and
      mortality registry files to determine cancer incidence and cause-specific
      mortality; thyroid screening examinations with ultrasound and fine-needle biopsy;
      and cryopreserved white blood cells and plasma for future molecular studies.
      Comprehensive studies of Chernobyl cleanup workers have potential to provide new
      information about cancer risks due to protracted exposures to ionizing radiation.

PMID- 9146711
TI  - The Estonian study of Chernobyl cleanup workers: II. Incidence of cancer and
      mortality.
AB  - A cohort of 4,742 men from Estonia who had participated in the cleanup activities
      in the Chernobyl area sometime between 1986 and 1991 and were followed through
      1993 was analyzed with respect to the incidence of cancer and mortality.
      Incidence and mortality in the cleanup workers were assessed relative to national
      rates. No increases were found in all cancers (25 incident cases compared to 26.5
      expected) or in leukemia (no cases observed, 1.0 expected). Incidence did not
      differ statistically significantly from expectation for any individual cancer
      site or type, though lung cancer and non-Hodgkin's lymphoma both occurred
      slightly more often than expected. A total of 144 deaths were observed
      [standardized mortality ratio (SMR) = 0.98; 95% confidence interval (CI) = 0.82
      1.14] during an average of 6.5 years of follow-up. Twenty-eight deaths (19.4%)
      were suicides (SMR = 1.52; 95% CI = 1.01-2.19). Exposure to ionizing radiation
      while at Chernobyl has not caused a detectable increase in the incidence of
      cancer among cleanup workers from Estonia. At least for the short follow-up
      period, diseases directly attributable to radiation appear to be of relatively
      minor importance when compared with the substantial excess of deaths due to
      suicide.

PMID- 9146712
TI  - History of mesenteric ischemia. The evolution of a diagnosis and management.
AB  - This article has traced the evolution of our knowledge of mesenteric ischemia
      from the initial stage of recognition of the condition and its manifestations,
      through the phase of treatment after the fact-resection of gangrenous intestine,
      to our present-day attempts to diagnose and treat the ischemic episode before
      death of the bowel and patient occurs. It is history from the authors'
      perspective, and because of limitations of space it is, perforce, highly
      selective. Hundreds of valuable contributions could not be included, and their
      omission in no way detracts from their importance. A number of surgeons,
      including Williams and Bergen in this country, Marston in England, Saegesser in
      Switzerland, and Kieny in France, have made mesenteric ischemia a major focus of
      their careers and have published extensively on it. The first book devoted to all
      aspects of mesenteric ischemia, Vascular Disorders of the Intestines edited by
      Boley, Schwartz, and Williams, was published in 1971. Since that time a number of
      books and monographs have chronicled progress in the field. Together these
      references make a good foundation for newly interested investigators in the
      subject. The results of diagnosis and management of mesenteric ischemia have
      improved significantly over the past 100 years but remain poor. The best part of
      the history of mesenteric ischemia remains to be written.

PMID- 9146713
TI  - The mesenteric circulation. Anatomy and physiology.
AB  - The purpose of this article is to review the angiographic appearance of the major
      visceral arteries, the more common variants, their embryologic origins, and some
      of the most common sources of collateral flow. A brief review of the physiology
      of the mesenteric circulation is also provided, including a discussion of the
      intrinsic and extrinsic mechanisms of splanchnic blood flow control.

PMID- 9146715
TI  - Nonocclusive mesenteric ischemia.
AB  - NOMI remains a challenging clinical entity that demands a heightened index of
      suspicion and an aggressive diagnostic and treatment strategy in order to avoid
      the untoward sequela of short bowel syndrome and to achieve survival. Early
      arteriographic diagnosis and prompt institution of vasodilator therapy have
      proven successful in reducing the high (70% to 90%) mortality rate observed
      through the 1980s to 50% to 55% during the last decade. Continued investigations
      into the pathophysiologic mechanisms underlying splanchnic vasospasm and
      intestinal IR injury will, it is hoped, add more alternate and effective
      therapies to the current armamentarium.

PMID- 9146714
TI  - Acute mesenteric ischemia.
AB  - The morbidity and mortality of acute mesenteric ischemia have remained high over
      the past 30 years despite heightened sensitivity to the diagnosis. Because the
      duration of the ischemic episode is the most significant determinant of outcome,
      an aggressive diagnostic and treatment protocol must be maintained. Although this
      stance may precipitate a number of negative angiographic studies, such an
      approach is the only opportunity for salvage in these critically ill patients.

PMID- 9146716
TI  - Mesenteric venous thrombosis.
AB  - MVT is an uncommon form of visceral ischemia. Symptoms and signs of MVT are
      usually nonspecific and should not be relied on for accurate diagnosis. A simple,
      logical diagnostic algorithm can be used to manage most of these patients (Fig.
      6). CT or MRI appears to be the most sensitive diagnostic test and should be
      obtained early for any patient suspected of harboring MVT. Patients with
      peritonitis require prompt abdominal exploratory laparotomy to rule out ischemic
      bowel. Once the diagnosis of acute MVT is confirmed, the patient should be
      anticoagulated with heparin. During operation, all nonviable bowel should be
      resected with intent for a second-look laparotomy after 24 hours if there is any
      question of ongoing ischemia. We recommend using fluorescein-assisted evaluation
      of marginally viable bowel intraoperatively. After the operation, anticoagulation
      is continued with heparin and then oral warfarin sodium when the patient's bowel
      function returns. For those patients without peritonitis, we recommend prompt
      anticoagulation followed by at least a 48- to 72-hour period of close
      observation. All patients who have had an episode of acute MVT and do not have a
      contraindication to anticoagulation should be anticoagulated on a life-long basis
      with warfarin sodium. Despite our increased awareness of acute MVT, the 30-day
      mortality rate remains high. Acute MVT typically has a more insidious and
      unpredictable course than do other forms of visceral ischemic syndromes, with a
      mortality rate as high as that of its arterial counterpart. Although there has
      been a slight improvement in survival during the last 20 years, the recurrence
      rate remains high and the long-term prognosis is poor in this group of patients.
      Survival of patients with chronic MVT is better than that of those with acute MVT
      and appears to be determined by the underlying disease.

PMID- 9146717
TI  - Duplex ultrasonography in evaluation of splanchnic artery stenosis.
AB  - Duplex ultrasonography accurately identifies high-grade stenoses in the SMA.
      Analysis of velocity data reveals few false positives and virtually no false
      negatives in the determination of high-grade SMA stenosis by duplex scanning. We
      therefore utilize duplex scanning to perform early screening studies of patients
      with symptoms suggestive of chronic visceral ischemia. If the duplex findings are
      negative, we recommend evaluating for other sources of abdominal pain. If the
      findings are positive, prompt angiography is indicated. It is important to
      remember that although duplex scanning can identify mesenteric artery stenosis,
      it cannot diagnose intestinal ischemia. By establishing duplex scanning as a
      useful and accessible noninvasive screening tool, it is hoped that the time
      between onset of visceral ischemic symptoms and diagnosis of chronic visceral
      ischemia will be shortened significantly, potentially reducing the morbidity and
      mortality of the disease.

PMID- 9146718
TI  - Chronic mesenteric ischemia. Clinical presentation and diagnosis.
AB  - Owing to a heightened awareness of the disease as well as improved diagnostic
      tests, chronic mesenteric ischemia is now recognized as a more common cause of
      abdominal pain. The classic symptoms of postprandial abdominal pain with weight
      loss are evident in the majority of proven cases; most patients also have other
      evidence of advanced atherosclerotic vascular disease. Several new diagnostic
      techniques are being developed and tested, most notably color duplex imaging,
      although angiography still remains the diagnostic gold standard. It is hoped that
      better noninvasive testing may eventually eliminate the need for angiography, as
      well as lead to a more expedient diagnosis of chronic mesenteric ischemia.

PMID- 9146719
TI  - Percutaneous transluminal mesenteric angioplasty.
AB  - The endovascular treatment of chronic mesenteric ischemia remains in its infancy.
      This state is most certainly related to the small patient population affected by
      this devastating condition and the surgeon's limited desire to pursue
      percutaneous options for this group. Surgical trepidation is not unwarranted
      because in many facets mesenteric angioplasty is similar to percutaneous carotid
      intervention. Interventions in these vessels represent manipulation of terminal
      and unduplicated arterial systems. Complications compromising flow to either
      vascular bed can yield rapid grave outcomes. Despite this risk, early experience
      with mesenteric angioplasty for chronic ischemia suggests that it is a viable
      treatment alternative and that it can be performed with relative safety. A
      randomized prospective trial of mesenteric angioplasty with operative bypass
      grafting appears to be the next logical step.

PMID- 9146720
TI  - Bypass grafting for chronic mesenteric ischemia.
AB  - A critical analysis of the literature suggests that there is no clearly superior
      technique for mesenteric revascularization and that the choice of operation must
      be individualized. Bypass grafting using either an antegrade or retrograde
      technique with prosthetic or autogenous conduits should produce excellent long
      term results for most patients with this complex surgical problem. In most
      situations multiple vessel revascularizations are preferred. Surgeons caring for
      such patients must have the ability to utilize all available techniques to ensure
      optimal outcomes.

PMID- 9146721
TI  - Transaortic mesenteric endarterectomy.
AB  - Although a number of methods for mesenteric artery reconstruction have been
      suggested, we believe that patients with atherosclerotic stenosis and occlusion
      of mesenteric vessels presenting with either acute or chronic visceral ischemia
      are best managed by either antegrade aortomesenteric bypass or transaortic
      mesenteric endarterectomy. Antegrade bypass is the most versatile technique and
      is therefore best adapted to extensive mesenteric disease. Transaortic mesenteric
      endarterectomy lends itself well to simultaneous renal artery endarterectomy when
      clinically significant osteal atherosclerosis is present at both sites. With any
      method of reconstruction, the technical adequacy of repair should be defined
      intraoperatively. In this regard, intraoperative duplex sonography provides both
      anatomic and hemodynamic data necessary to ensure technical success and late
      patency.

PMID- 9146722
TI  - Celiac artery compression syndromes.
AB  - Compression of the visceral arteries can produce true mesenteric ischemia, but
      the syndrome is rare. The syndrome is caused by unfavorable anatomic
      relationships at the aortic hiatus among the CA, the SMA, and overlying
      structures, particularly the diaphragmatic crura. These anatomic relationships,
      in contrast to the syndrome they sometimes produce, are relatively common, which
      makes the detection of CA compression only a prerequisite to the diagnosis of the
      clinical entity. The diagnosis of CA compression syndrome ultimately depends on
      the relentless elimination of other possible causes for abdominal pain and on the
      knowledge that this curious syndrome does indeed exist. If properly diagnosed,
      the CA compression syndrome can be corrected with a safe, relatively simple
      surgical procedure. Past treatment series reflect too little appreciation for the
      extensiveness of a true, chronic CA injury. Revascularization of the CA, in
      addition to release of compression, should therefore be performed with greater
      frequency in the future. The young patients who are successfully diagnosed and
      treated for this unusual syndrome are frequently entirely relieved of long
      standing, debilitating pain, and, like other patients with chronic mesenteric
      ischemia, they typically enjoy dramatic improvement in the quality of their
      lives. Thus, with the prospect of these patients in mind, a clinician should
      accept the opinion that the syndrome "does not exist" only after careful
      consideration of the entire literature.

PMID- 9146723
TI  - Visceral artery aneurysms.
AB  - Visceral artery aneurysms are an uncommon form of vascular disease that have a
      significant potential for rupture or erosion into an adjacent viscera, resulting
      in life-threatening hemorrhage. During the last decade, hepatic artery aneurysms
      have become the most commonly reported visceral artery aneurysm. This change
      likely reflects the increased use of percutaneous diagnostic and therapeutic
      biliary procedures, as well as increased use of diagnostic computed tomography
      after blunt abdominal trauma. A second significant development is the increased
      use of percutaneous catheter-based therapy in the management of visceral artery
      aneurysms. Nonetheless, a continued aggressive approach to the diagnosis and
      management of these unusual aneurysms remains warranted.

PMID- 9146724
TI  - Mesenteric revascularization during aneurysmectomy.
AB  - The most important association between aortic aneurysm surgery and the mesenteric
      circulation is the potential for inadvertent compromise to the mesenteric trunks
      and their end organs. Preservation of visceral blood flow is a critical objective
      in each case, using methods that have been developed as techniques for suprarenal
      abdominal and thoracoabdominal aneurysmectomy have evolved. Beyond simply
      preserving what existed, revascularization by endarterectomy or bypass has a role
      in selected cases to improve the natural history of advanced mesenteric occlusive
      disease, although the rationale for such prophylactic surgery must remain
      relatively weak until more is learned about disease progression in the visceral
      arteries. Finally, a small number of patients with mesenteric ischemic symptoms
      at the time of aneurysmectomy clearly benefit from combined surgery.

PMID- 9146725
TI  - Ischemic colitis.
AB  - This article contains a current review of ischemic colitis, including its
      etiology, pathophysiology, diagnostic modalities, and treatment options. A
      special emphasis is given to ischemic colitis following aortic reconstruction.

PMID- 9146726
TI  - Unusual causes of mesenteric ischemia.
AB  - Although complications of generalized atherosclerosis most commonly cause
      intestinal ischemia, a number of unusual causes may be responsible. These unusual
      causes can be grouped into six major categories: (1) mechanical, (2) drugs, (3)
      hematologic, (4) endocrine, (5) vasculopathies, and (6) miscellaneous. Morbidity
      and mortality rates remain high because these rare diseases frequently go
      unrecognized until patients suffer adverse outcomes. A high index of suspicion
      may decrease the delay in diagnosis of mesenteric ischemia caused by these
      disorders.

PMID- 9146727
TI  - pp32 overexpression induces nuclear pleomorphism in rat prostatic carcinoma
      cells.
AB  - Nuclear pleomorphism is an important diagnostic factor in tumour pathology.
      Traditionally, nuclear pleomorphism is evaluated qualitatively or
      semiquantitatively, often as a component of tumour grade; the molecular basis of
      nuclear pleomorphism, however, remains unclear. In this study, we investigated
      the quantitative effects on nuclear morphology of overexpressing pp32, a recently
      described nuclear phosphoprotein highly expressed in self-renewing and neoplastic
      cell populations. Assessment of Feulgen-stained transfected and control lines of
      AT3.1, a rat prostatic carcinoma cell line, using a computerized Cellular Image
      Analysis System (BD CAS-200) showed that stable overexpression of human pp32 in
      AT3.1 cells is accompanied by marked increases in the coefficient of variation of
      nuclear shape, nuclear size and chromatin textures but not in DNA content. In
      contrast, stable transfection with control vector, with ras, or with bcl-2 failed
      to affect nuclear morphology. Cell cycle analysis further showed that pp32
      related increases in variation of nuclear structure manifested principally in G1.
      These studies suggest that pp32 plays a role either directly or indirectly in the
      control of nuclear shape of G1 cells.

PMID- 9146728
TI  - Elevated levels of ERK2 in human breast carcinoma MCF-7 cells transfected with
      protein kinase C alpha.
AB  - We investigated the effect of elevated levels of protein kinase C alpha (PKC
      alpha) on cell proliferation in human breast carcinoma cells (MCF-7). MCF-7 cells
      transfected with either the pSV2M(2)6 vector without the insert (MCF-7/Vector) or
      containing a full length cDNA encoding PKC alpha (MCF-7/PKC alpha) were compared.
      MCF-7/PKC alpha cells were found to have an increased proliferative rate with a
      doubling time of 15 h as compared to 42 h for MCF-7/Vector cells. Flow cytometry
      illustrated a greater percentage of MCF-7/PKC alpha cells in the S phase of the
      cell cycle. Western and Northern blot analyses demonstrated an increase in
      extracellular regulated protein kinase 2 (ERK2) gene expression in MCF-7/PKC
      alpha cells but no alteration of this gene expression in MCF-7/Vector cells.
      These results suggested that the elevated level of ERK2 which is also known as
      mitogen activated protein kinase is probably involved in the increase in MCF
      7/PKC alpha cell proliferation.

PMID- 9146729
TI  - Cell density downregulates DNA synthesis and proliferation during osteogenesis in
      vitro.
AB  - The classical models of in vitro cell culture comprise fibroblasts and epithelial
      cells. Osteogenic cells represent another interesting cell model; however, it is
      not known whether during osteogenesis cell density regulates cell growth as seen
      in cultures of fibroblasts and epithelial cells. We selected MC3T3-E1 cells for
      study because they are an osteogenic cell line that, when subcultured, grow to
      confluence and form multilayers of cells in conventional cultures by continued
      proliferation, as do fibroblasts. Once maximum cell density is obtained,
      proliferation is down regulated resulting in a mixed population of quiescent and
      dividing cells. We used this model to determine whether downregulation of
      proliferation as expressed by cell number and DNA synthesis is cell density
      dependent. MC3T3-E1 cells were cultured over a period of 34 days to determine
      their kinetics, viability, ability to synthesize DNA, distribution within phases
      of the cell cycle and cell number-response relationships. Our results show that
      (1) viability ranged between 92% and 96% and the cell number 2.5 x 10(5) per cm2
      once cultures reached steady state, (2) most cells entered the G0/G1 phase of the
      cell cycle on day 7, (3) there was no correlation between the proportion of cells
      in S phase and downregulation of DNA synthesis, (4) a direct relationship exists
      between cell density and downregulation of DNA synthesis on day 8, (5) the
      minimum time for cells to be cultured before downregulation of DNA synthesis
      begins is independent of cell number, and (6) downregulation of DNA synthesis is
      reversible. These results suggest that density-dependent downregulation of DNA
      synthesis may be a mechanism of growth control for osteogenic cells in vitro that
      operates more like density-dependent growth control in cultures of fibroblasts
      rather than epithelial cells.

PMID- 9146730
TI  - Characterization of label-retaining cells in the epidermis of a human skin
      equivalent.
AB  - The human skin equivalent (HSE) is an in vitro reconstructed model that resembles
      skin morphologically and biochemically. The HSE is formed by overlaying a
      fibroblast-populated collagen matrix with a suspension of epidermal cells. Basal
      keratinocytes attach to the dermal equivalent via a newly formed basement
      membrane and multiply to form a stratified, differentiated epidermis. The aim of
      the studies described here was to characterize the basal cells of the HSE in
      terms of their cell cycling potential. The experiments utilized long-term
      labelling of the cells with tritiated thymidine ([3H]dT), followed by irradiation
      with ultraviolet light. [3H]dT incorporation was analysed via routine
      autoradiography. Irradiation with 100 J/m2 UV light increased the number of
      labelled basal cells by 58% over the control, the maximal stimulation observed.
      Decreased numbers of labelled basal cells were observed at doses of UV light
      greater than 100 J/m2. The maximal number of labelled basal cells was observed on
      day 14 and decreased over time; the number of labelled suprabasal cells increased
      concomitantly. Label-retaining cells (12%) persisted in the stratum basale of
      control HSEs after 32 days in culture. Labelled cells were observed in the apical
      layers of the stratum granulosum of control HSEs after 22 days in culture. These
      data suggest that the stratum basale of the HSE contains a population of slow
      cycling cells whose characteristics resemble a subpopulation of slowly cycling
      cells found in normal human skin.

PMID- 9146731
TI  - Mutagenic heterocyclic aromatic amines (HAAs) in 'processed food flavour'
      samples.
AB  - Eight samples of 'processed food flavours' (PFFs), chosen from five different
      categories, were analysed for their mutagenic activity using the Ames Salmonella
      assay, and also for the presence of eight heterocyclic aromatic amines (HAAs),
      namely 2-amino-3-(trideuteromethyl)imidazo[4,5-f]quinoline (IQ), 2-amino-3,8
      dimethyl-imidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline (MeIQx), 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (7,8
      DiMeIQx), 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (4,7,8-TriMeIQx), 2
      amino-I-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 3-amino-1,4-dimethyl-5H
      pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P
      2) using liquid chromatography and mass spectrometry (LC/MS). The isolation of
      HAAs was based on sequential liquid-liquid extraction procedures of samples at
      both acidic and basic pH values. The recoveries and the clean-up were monitored
      by introduction of quality control samples and by spiking with three tri
      deuterated standards of HAAs. Although the results for the mutagenicity assay
      were comparable by testing less-purified and highly-purified extracts, the
      analysis for identification and quantification of HAAs by LC/MS required highly
      purified concentrates. Four samples had little or no mutagenic activity and these
      results were in agreement with their LC/MS results: they had no detectable levels
      (detection limits 1-3 ppb) of any of the HAAs monitored. The mutagenic activity
      of one sample was in complete agreement with the quantification of HAAs by LC/MS.
      Two samples produced strong mutagenic responses (3115 and 2664 revertants/g). In
      one sample, LC/MS analysis revealed the presence of 9.6 ppb IQ, whereas LC/MS of
      the other could not confirm the presence of any of the eight HAAs monitored. Two
      samples produced mild mutagenic activity (204 and 160 revertants/g), but
      relatively elevated concentrations of IQ (6.7 and 6.8 ng/g) by LC/MS. The
      extracts from all samples were tested for their modifying effects on mutagenicity
      of four HAAs. The discrepancy between the Ames test and the LC/MS analysis of
      some samples indicates several possibilities, such as the presence of some other
      HAAs, of their isomers or of other mutagens. In addition, the presence of mutagen
      modifiers (inhibitors or synergists) was observed in most samples. The results
      indicate that although chemical tests (e.g. LC/MS) can provide quantitative data
      for the HAAs monitored, the Ames mutagenicity test should also be conducted to
      determine the mutagenic activities of PFFs, in order to assess their health risk
      potential.

PMID- 9146732
TI  - Heterocyclic aromatic amine content in pre-processed meat cuts produced in
      Canada.
AB  - In an ongoing survey, the presence of heterocyclic aromatic amines (HAAs) was
      determined in processed, ready-to-eat meat products sold as 'meat cuts'. HAAs are
      a group of recently recognized mutagenic/carcinogenic contaminants in foods that
      are produced during the heat processing of meat. 16 samples of meat cuts (e.g.
      turkey breast, salami, chicken loaf, cooked ham, all beef meat, pepperoni, etc.),
      randomly purchased from supermarkets and specialty food stores in the Ottawa
      area, were analysed for the presence of eight HAAs. The isolation of HAAs was
      based on sequential liquid-liquid extraction procedures of the samples at both
      acidic and basic pH values. The mutagenic activity of these samples was
      determined using the Ames/Salmonella microsome assay with the strain TA98 plus
      rat liver S-9 metabolic activation. The mutagenicity of these samples ranged from
      undetectable to slightly active. The highest mutagenic activity, 141 induced
      revertants/g, was found in a smoked turkey breast sample. 11 samples were not
      mutagenic, including two that indicated a tendency for inhibition of the
      spontaneous revertants. The remaining four samples exhibited very low mutagenic
      activity. For chemical analysis, the extracts were purified with two solid phase
      extraction cartridges. Quantitative analysis was performed by using liquid
      chromatography for separation and mass spectrometry for detection. With the
      exception of trace amounts (0.4 ng/g) of 2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline (MeIQx) in the sample with highest mutagenic activity, the chemical
      analysis did not detect the presence of any of the eight most frequently found
      HAAs in fried or broiled meat products. These data suggest that consumption of
      meat cuts does not present a serious health risk from HAA-type contaminants.

PMID- 9146733
TI  - Safety evaluation of tannase enzyme preparation derived from Aspergillus oryzae.
AB  - Tannase is an acylhydrolase enzyme preparation from Aspergillus oryzae that can
      be used as a processing aid for the manufacture of cold water-soluble tea
      beverages. A 91-day oral toxicity study in the rat and a gene mutation study in
      Salmonella typhimurium were performed to establish the safety of the enzyme
      preparation for the consumer. General toxicity was low, with no adverse effects
      observed at the highest dose tested, 1% in the diet. There was no evidence of
      mutagenic potential with or without metabolic activation. These results, together
      with knowledge of the production organism and the chemical and microbiological
      characterization of the enzyme preparation, indicate that tannase can be regarded
      as safe for its intended use in processing tea.

PMID- 9146734
TI  - Direct mutagenicity of the polycylic aromatic hydrocarbon-containing fraction of
      smoked and charcoal-broiled foods treated with nitrite in acid solution.
AB  - The polycyclic aromatic hydrocarbons (PAH) containing fractions of smoked and
      charcoal-broiled foods, namely, Sheat fish (Kytopterus apogon), Mimrow
      (Crossocheilus reba), Freshwater catfish (Clarias batrachus), chicken wings, rice
      pork sausage and pork, in addition to naphthalene, acenaphthene, anthracene,
      phenanthrene, fluoranthene, pyrene, benz[a]anthracene, naphthacene,
      benzo[a]pyrene, benzo[e]pyrene, 9,10-dimethyl-1,2-benzanthracene,
      dibenz[ah]anthracene, benzo[ghi]perylene and coronene, were evaluated for their
      mutagenic potential using Salmonella typhimurium strains TA98 and TA100 in the
      absence of metabolic activation after being treated with nitrite (500 mM) for 4
      hr at 37 degrees C and in acid solution pH 3.0-3.5. The presence of N-nitroso
      compounds was also determined. Results showed that nitrite could convert most
      samples to direct-acting mutagens towards both strains except for fluoranthene
      and benzo[ghi]perylene, which exhibit mutagenicity only with TA98. It was
      demonstrated that treatment of PAHs with nitrite in acid solution produced some
      non-N-nitroso direct-acting mutagens, suggesting that they might belong to nitro
      PAHs. Therefore, the consumption of charcoal-broiled and smoked foods
      simultaneously with nitrite is not recommended.

PMID- 9146735
TI  - Potential nitrosamine formation and its prevention during biological
      denitrification of red beet juice.
AB  - High nitrate intake has been shown to result in an increased risk of endogenous
      formation of N-nitroso compounds. Certain vegetables and vegetable juices contain
      high concentrations of nitrate. Biological denitrification using strains of
      Paracoccus denitrificans (P.d.) has been proposed as effective means to reduce
      nitrate contents in such vegetable juices. During this bacterial denitrification
      process, substantial nitrite concentrations are transiently formed. This study
      investigated whether N-nitrosation reactions might occur. The easily nitrosatable
      amine morpholine was added to red beet juice at high concentration (100 ppm)
      during denitrification 10 different batches of red beet juice served as raw
      material. Each batch was submitted to denitrification in the presence and absence
      of ascorbic acid. In the absence of ascorbic acid, formation of N
      nitrosomorpholine (NMOR) was observed in the low ppb range (0.5-8 ppb). Addition
      of ascorbic acid (500 mg/litre) inhibited the formation of NMOR, except for those
      instances where the pH was less than 6 and/or nitrate turnover was low (< 200 mg
      NO3-/litre/hr). Under conditions leading to high rates of nitrate turnover (> 200
      mg NO3-/litre/hr), nitrosamine formation can reliably be prevented by ascorbic
      acid. The results show that bacterial denitrification of red beet juice high in
      nitrate can be accomplished without the risk of nitrosamine formation.

PMID- 9146736
TI  - Subchronic oral toxicity of di-n-octyl phthalate and di(2-Ethylhexyl) phthalate
      in the rat.
AB  - The subchronic oral toxicity of di(2-ethylhexyl) phthalate (DEHP) and di-n-octyl
      phthalate (DNOP) was studied. Groups of 10 male and 10 female Sprague-Dawley rats
      were administered DEHP in the diet at 0, 5, 50, 500 or 5000 ppm for 13 wk. In a
      separate study, groups of 10 male and 10 female Sprague-Dawley rats were given
      DNOP (5, 50, 500 and 5000 ppm) in the diet while control groups received basal
      diet containing 4% corn oil and positive control groups were fed a diet
      containing 5000 ppm DEHP. Growth rate and food consumption were not affected by
      treatment with either compound. Hepatomegaly was observed in the highest dose
      groups of both sexes administered DEHP but not in the DNOP-treated animals. At
      the highest dose, DNOP caused threefold (females) and 12-fold (males) increases
      in liver ethoxyresorufin-O-deethylase activity while DEHP did not. Mild changes
      in serum biochemistries were mostly confined to rats in the highest dose group of
      DEHP, and included increased serum albumin and albumin/globulin ratio in both
      sexes and decreased cholesterol in female rats. Mild vacuolations in the Sertoli
      cells were observed in male rats exposed to 500 ppm DEHP. At 5000 ppm DEHP, there
      was mild to moderate seminiferous tubule atrophy and Sertoli cell vacuolation in
      males, and rats of both sexes showed hepatic peroxisome proliferation. Both DEHP
      and DNOP at 5000 ppm caused mild histological changes in the thyroid consisting
      of reduced follicle size and colloid density, and the liver consisting of
      endothelial nuclear prominence, nuclear hyperchromicity and anisokaryosis. There
      was accentuation of zonation of the hepatic lobules and increased perivenous
      cytoplasmic vacuolation in DNOP-treated rats. Trace quantities (3-5 ppm) of DEHP
      and DNOP were detected in the liver, and 15-31 ppm were found in adipose tissue
      of the highest dose groups. The no observed-effect-level was judged to be 50 ppm
      in the diet or 3.7 mg/kg body weight/day for DEHP, and 500 ppm or 36.8 mg/kg body
      weight/day for DNOP.

PMID- 9146737
TI  - Evaluation of a novel assay of potential toxicity/neurotoxicity of carpet
      emissions (VOCs) in mice.
AB  - A private testing laboratory utilizing the whole-body plethysmograph/head-only
      exposure apparatus outlined in the respiratory irritation assay ASTM E981-84,
      along with a novel exposure regimen, has reported neurotoxic effects and
      mortality in mice exposed to relatively low levels of volatile organic compounds
      (VOCs) emitted from a number of consumer products. This methodology was evaluated
      by exposing groups of mice, including unrestrained and sham-treated animals, to
      VOCs generated from a sample of carpet reported to be neurotoxic using the
      modified assay. General toxicological (haematological measurements, organ
      weights, gross pathology, histopathology) and specific neurotoxicity (functional
      observations, body temperature, histopathology of nervous tissues) parameters
      were evaluated. No effects related to exposure to carpet VOCs were observed in
      the mice. However, despite careful handling, a number of effects were observed
      which were attributed to the repeated restraint of mice in the ASTM E981
      apparatus. These included a number of minor physical injuries, decreased body
      weights, altered thymus weights, compression damage to the liver and haemorrhage
      of the pituitary gland. It was concluded that the modification of the original
      ASTM E981 methodology may result in physical injuries and stress which may
      significantly affect any evaluation of toxicity and neurotoxicity in treated
      animals and result in inaccurate conclusions.

PMID- 9146738
TI  - Interlaboratory evaluation of a human patch test for the identification of skin
      irritation potential/hazard.
AB  - The human 4 hr patch test provides an opportunity to identify substances with
      significant skin irritation potential without recourse to the use of animals. To
      demonstrate the validity of the method it must be relevant and reliable. It is
      self-evident that the method is relevant to the identification of skin irritation
      hazards to humans. However, it is essential that the results be reproducible.
      This paper presents data on a number of substances tested by different
      laboratories. Eight substances were tested by two or more laboratories and the
      data compared with a standard positive control, 20% sodium dodecyl sulfate. In
      almost all cases, the outcome of this comparison was identical. Thus, despite the
      fact that there is known variability among human subjects in terms of skin
      reactivity to irritants, this simple method showed good reproducibility for the
      classification of acute skin irritation potential. Therefore, it is argued that
      this human 4-hr patch test is a valid alternative to the equivalent rabbit test
      for the assessment of skin irritation hazard to humans.

PMID- 9146739
TI  - A re-appraisal of the skin-sensitizing activity of 2,4-dinitrothiocyanobenzene.
AB  - A debate continues regarding the immunological properties of 2,4
      dinitrothiocyanobenzene (DNTB). In some investigations this chemical was shown
      not to cause skin sensitization when applied topically but to induce instead
      hyporesponsiveness or immunological tolerance. In other studies DNTB was found to
      cause skin sensitization, but not tolerance. However, this chemical continues to
      be used to discriminate between the properties of skin sensitizing and non
      sensitizing chemicals. This study demonstrates that topical exposure of mice to
      DNTB induces skin sensitization in mice and that this is associated with the
      accumulation of dendritic cells in draining lymph nodes and the stimulation of
      lymph node cell proliferation; the latter responses being of equivalent magnitude
      to those stimulated by 2,4-dinitrochlorobenzene (DNCB), a chemical known to cause
      contact sensitization. Moreover, exposure of mice to DNTB, as with exposure to
      DNCB, resulted in the development of a cytokine secretion pattern by draining
      lymph node cells (LNC) characteristic of contact allergens. Thus, DNTB and DNCB
      each induced the production by LNC of high levels of interferon-gamma, but little
      or no interleukin 4 or interleukin 10. Finally, DNTB was shown in the guinea pig
      maximization test to behave as an extreme skin sensitizer. These results confirm
      that DNTB should not be regarded as a universal tolerogen and that it possesses a
      significant potential to induce contact sensitization. The use of this chemical
      as a presumptive non-sensitizer and/or tolerogen for the evaluation of the
      selectivity of new predictive test methods for the identification of contact
      allergens is therefore considered to be inappropriate.

PMID- 9146740
TI  - Evaluation of the aetiological role of dietary salt exposure in gastric and other
      cancers in humans.
AB  - The findings in laboratory and epidemiological studies relevant to the assessment
      of salt for carcinogenic potential are reviewed. Associations between the high
      consumption of certain highly salted foodstuffs, particularly in some oriental
      countries, and increased risk of cancer of the stomach do not incriminate salt
      per se. Some highly spiced foods contain potent genotoxic carcinogens,
      irrespective of whether they also contain salt. There is evidence in laboratory
      animals that high concentrations of salt may increase the incidence of gastric
      cancer caused by such carcinogens. This may well be attributable to a marked and
      sustained regenerative response in the gastric mucosa of laboratory animals
      chronically exposed to the cytotoxicity of hyperosmolar concentrations of salt,
      such a mitogenic response favouring the progression towards neoplasia. However,
      there is no laboratory evidence whatsoever to indicate that salt per se is a
      carcinogen for any site in the body; neither is there any reliable
      epidemiological evidence to indicate that dietary salt affects the incidence of
      gastric or other cancers. A particular problem in the interpretation of
      epidemiological studies is that the consumption of diets containing highly
      salted, spicy foods is often associated with low intakes of fruit and green
      vegetables, which contain cancer-protective antioxidants. In Western countries
      the incidence of cancer of the stomach has been falling for some 50 years. The
      consensus view is that this fall is attributable to improved food hygiene and
      increasingly available facilities for refrigeration. There are no grounds for
      supposing that the fall is attributable to a decreasing intake of salt. A high
      dietary salt intake does not necessarily entail exposure to salt in
      concentrations high enough to damage the gastric mucosa. The typical Western diet
      would not be expected to provide such high salt concentrations. It is concluded
      that there are no grounds for believing that a reduction in the average daily
      salt intake in the Western diet would have any effect on the risk of developing
      any form of cancer.

PMID- 9146741
TI  - "Report of the Rodent Bladder Carcinogenesis Working Group".

PMID- 9146742
TI  - Psychosomatic, psychiatric and neurological aspects of concussive syndromes in
      industry.

PMID- 9146743
TI  - Medico-legal aspects of traumatic neurosis.

PMID- 9146744
TI  - Impartial medical experts.

PMID- 9146746
TI  - Establishing justice in the field of damage law.

PMID- 9146745
TI  - The Industrial Commission looks at industrial head injuries.

PMID- 9146747
TI  - Blood flow to the haemopoietic bone marrow.
AB  - In order to maintain an adequate haemopoiesis, the bone marrow is dependent on a
      sufficient blood supply. Our understanding of the regulation of marrow perfusion
      remained patchy for several decades, mainly because of technological
      difficulties. Recent advances in methodology have permitted more detailed
      analyses of bone marrow perfusion. Enhanced stimulation of erythropoietic or
      leucopoietic activity leads to increased blood flow to the bone marrow. There is
      evidence that this vasodilatory effect is mediated by the cytokines
      erythropoietin and granulocyte colony-stimulating factor; however, a direct link
      has yet to be firmly established. The presence of receptors for several other
      cytokines on vascular endothelial and smooth muscle cells suggests that these may
      also have a regulatory role. The vasodilating factor nitric oxide (NO) regulates
      bone marrow blood flow both under normal conditions and during accelerated
      haemopoiesis, and NO is possibly induced via activation of cytokine receptors.
      There are conflicting reports as to how catecholamines affect marrow vascular
      tone. Although there is firm evidence that the bone marrow vasculature is
      innervated, no definite role of this innervation in vasoregulation has been
      documented. Advances in bone marrow/blood stem cell transplantation technology
      and the development of other therapeutic strategies for bone marrow failure may
      in part be dependent on optimization of the blood supply to the haemopoietic bone
      marrow.

PMID- 9146748
TI  - Impaired leucocyte rolling, adhesion and transendothelial migration following
      cuprophane haemodialysis.
AB  - In this study, we investigated how different steps in the extravasation process
      of leucocytes, i.e. rolling, adhesion and transendothelial migration, are
      affected by haemodialysis with cuprophane membranes. Human leucocytes obtained
      from whole blood prior to clinical haemodialysis and from the afferent blood line
      (post-dialyser) 15 min after the initiation of dialysis were injected into the
      mesenteric microcirculation of urethane anaesthetized rabbits and analysed for
      their ability to roll in the microvessels by use of intravital fluorescence
      microscopy. Moreover, neutrophils from the two leucocyte populations were
      compared with respect to chemoattractant-induced adhesion and transmigration
      across confluent monolayers of bovine aortic endothelial cells. Our results show
      that, as compared with pre-dialysis leucocytes, 15 min of cuprophane
      haemodialysis impaired leucocyte rolling by 78 +/- 7%, reduced N-formyl-methionyl
      leucyl-phenylalanin (fMLP)-induced adhesion by 34 +/- 9%, and abolished
      transendothelial migration. These findings demonstrate that intradialytical
      activation of leucocytes during cuprophane haemodialysis severely affects
      leucocyte functions that are critical in the extravasation process of these cells
      at inflammatory tissue sites, and thus may help explain the increased
      susceptibility to infections observed in patients on chronic haemodialysis.

PMID- 9146749
TI  - Adrenalectomy reduces the ability of newborn rats to gasp and survive anoxia.
AB  - The ventilatory response to anoxia in unanaesthetized rat pups of 1 and 8 days of
      age was studied. Ventilation was recorded by barometric plethysmography. During
      acute anoxia (100% N2), animals of both ages responded with hyperpnoea, primary
      apnoea, hypoxic gasping and secondary apnoea. After secondary gasping, occasional
      gasps occurred. If oxygen was administered during the gasping period, all animals
      survived through autoresuscitation. The duration of the period of hypoxic gasping
      was significantly longer in the 1-day-old animals. Adrenalectomy reduced the
      length of this period in both 1- and 8-day-old animals. In a second series of
      experiments, the effect of adrenergic antagonists on autoresuscitation was
      examined. Pretreatment with the non-selective alpha-receptor antagonist
      phentolamine reduced the duration of gasping in 1-day-old rats, but prolonged
      this duration in 8-day-old rats. The non-selective beta-receptor antagonist
      propranolol did not affect the duration of gasping in 1-day-old rats, whereas it
      prolonged this period in the older animals. We conclude that proper duration of
      gasping during anoxia is dependent on intact adrenal function and that the
      adrenal glands therefore play an important role in autoresuscitation from anoxia
      during postnatal life. The underlying mechanism appears to involve alpha
      adrenergic receptors.

PMID- 9146750
TI  - An isolated blood-perfused guinea-pig lung model for simultaneous registration of
      haemodynamic, microvascular and respiratory variables.
AB  - We have developed an optimized isolated lung perfusion system, which possesses
      several advantages. Firstly, studies of microvascular, respiratory,
      haematological and biochemical variables are combined in one model. Secondly,
      blood perfusion resulted in less oedema formation than buffer-perfused lungs, and
      high PO2 through ventilation with room air. Finally, data for the variables can
      be displayed, controlled and recorded in real time using a computerized system
      permitting subsequent processing (e.g. filtering without destroying original
      data). In this paper we discuss the basic behaviour of the model in terms of
      vascular resistance, vascular permeability, respiration and neutrophil
      sequestration. In addition, the effects of oleic acid, histamine and histamine
      receptor blockers were tested, and two methods of calculating vascular
      permeability are discussed. The way in which different anaesthetics affect the
      neutrophil content of lung tissue and blood was also investigated. In the model,
      oleic acid increased pulmonary vascular resistance and permeability, whereas
      histamine did not affect either permeability or the pre/postcapillary vascular
      resistance ratio. However, histamine receptor blockers increased this ratio,
      indicating that there was endogenous histamine release. The neutrophil content of
      the isolated lungs was increased, but this did not affect the variables measured.
      There was also accumulation of neutrophils in the lungs of blood donor animals,
      due to CO2 sedation. However, CO2 sedation proved to be superior to pentobarbital
      or ketamine anaesthesia in maintaining the levels of neutrophils circulating in
      the blood. In conclusion, this model seems to be sensitive and to yield
      reproducible results regarding the physiology or pathophysiology of the lung.

PMID- 9146751
TI  - Role of increased insulin demand in the adaptation of the endocrine pancreas to
      pregnancy.
AB  - During gestation the demand for insulin increases due to a decrease in insulin
      sensitivity of the maternal tissues. Simultaneously, pancreatic islet-cell
      proliferation, as well as insulin production and secretion increase. Both
      phenomena appear to be caused by the actions of pregnancy hormones. We studied
      the relationship between the two phenomena by investigating whether the supply of
      exogenous insulin affects the secretion of pregnancy hormones and islet function
      during gestation. For that purpose rats were treated with high doses of insulin
      (4.8 IU day-1 by sub-cutaneous osmotic mini pumps) so that the endogenous demand
      for insulin was fully satisfied from day 8-14 of gestation. Euglycaemia (5.0 mM)
      was maintained by intra venous infusion of glucose. The treatment suppressed
      insulin synthesis, as measured by in situ hybridization, in both pregnant and
      cyclic rats. In addition, in pregnant rats the increments in insulin secretion
      and in islet-cell proliferation were partly prevented. Furthermore, the data also
      suggest that in pregnant rats the treatment partly prevented the decrease in
      insulin sensitivity. Finally, the treatment did not affect the plasma
      concentrations of progesterone, prolactin and placental lactogen, but prevented
      the rise in growth hormone concentrations in pregnant rats. The present data
      suggest that, next to direct effects of pregnancy hormones and growth hormone on
      the pancreatic islets, a decreased insulin sensitivity in the maternal tissues,
      induced by actions of the same hormones, is involved in the regulation of islet
      function during gestation.

PMID- 9146753
TI  - Effect of cimetidine on basal and postprandial plasma concentrations of
      cholecystokinin and gastrin in humans.
AB  - Cimetidine reduces the appetite and weight in healthy overweight subjects.
      Gastrointestinal regulatory peptides such as cholecystokinin (CCK) have been
      proposed to mediate the satiety signal from gut to brain. Therefore, the effect
      of cimetidine on basal and postprandial plasma concentrations of cholecystokinin
      and gastrin was studied. After an overnight fast, 12 healthy volunteers were
      given cimetidine (400 mg) on day 1, breakfast on day 2, and cimetidine 20 min
      before breakfast on day 3. Plasma concentrations of cholecystokinin and gastrin
      were measured by radioimmunoassay. Plasma cholecystokinin concentration increased
      with one major peak observed 30 min and one smaller peak observed 120 min after
      intake of cimetidine. The meal induced an increase in the plasma concentration of
      cholecystokinin, while cimetidine prior to the meal elicited a sustained
      postprandial cholecystokinin response. Cimetidine had no effect on the basal
      plasma concentration of gastrin. The meal induced an increase in the plasma
      concentration of gastrin, while cimetidine prior to the meal elicited a sustained
      postprandial gastrin response. In conclusion, cimetidine increases the basal
      concentration of plasma cholecystokinin and elicits a sustained postprandial
      response of both cholecystokinin and gastrin. At least the cholecystokinin
      response may be one mechanism by which cimetidine reduces the appetite.

PMID- 9146752
TI  - Immunohistochemical localization of gastrin/CCK-B receptors in the dog and guinea
      pig stomach.
AB  - Gastrin/CCK-B receptors are involved in the regulation of several types of cells
      of the gastric mucosa, including the parietal cells, the ECL cells and the D
      cells. In this study, we aimed at localizing such receptors in the gastric
      mucosa. For this purpose, we prepared monospecific antibodies against two
      sequences of the canine gastrin/CCK-B receptor. Sections of formalin-fixed,
      paraffin-embedded corpus and antrum from dog and guinea-pig were immunostained
      with these antibodies. In parallel, sections were stained with antibodies against
      somatostatin. Staining with gastrin/CCK-B receptor antibodies was observed in a
      few, small epithelial cells in the bottom part of the corpus mucosa.
      Immunoreactive cells of the antral mucosa were structurally similar, but more
      frequent. The same cells also stained with somatostatin antibodies. In addition
      one of the gastrin/CCK-B antibodies reacted with canine submucosal smooth muscle
      cells. No staining was observed in sections exposed to antibodies that were pre
      absorbed with the corresponding antigen. We conclude that gastrin/CCK-B receptors
      are present in D cells of the gastric mucosa and in submucosal smooth muscle
      cells.

PMID- 9146754
TI  - Effects of reduced muscle temperature on the oxygen uptake kinetics at the start
      of exercise.
AB  - The purpose of this study was to examine the effects of reduced muscle
      temperature (Tm) on gas exchange kinetics and haemodynamics at the start of
      exercise. Six male subjects performed moderate cycle exercise under reduced (C)
      and normal (N) Tm conditions. Tm and rectal temperature were significantly
      reduced by immersion in cold water (by 6.6 degrees C and 1.8 degrees C,
      respectively). The increases in oxygen uptake (Vo2) and oxygen pulse (Vo2/HR)
      during phase 1 (abrupt increase after the start of exercise) were significantly
      lower under C than under N. The time constant for O2 under C (36.0 +/- 7.7 (SD)s)
      was significantly greater than under N (27.5 +/- 4.4 s); however, the time
      constants of cardiac output under C (38.3 +/- 16.6 s) and N (33.7 +/- 18.5 s)
      were similar. These results suggest that the slower Vo2 on-response under reduced
      Tm conditions is caused by decreased O2 extraction in working muscle and/or by
      impairment of oxidative reactions by reduced muscle temperature.

PMID- 9146755
TI  - Endurance training effects on neurotransmitter release in rat striatum: an in
      vivo microdialysis study.
AB  - In the present study we use the in vivo microdialysis sampling technique to
      register extracellular levels of neurotransmitters in the striatum of trained and
      untrained rats. We further evaluate the influence of 1 h of exercise on the
      striatal release of dopamine (DA), noradrenaline (NA), glutamate (GLU) and gamma
      aminobutyric acid (GABA) in trained and untrained rats. Male Wistars were
      randomly assigned to a training or control group. The exercise training consisted
      of running on a treadmill for 6 weeks, 5 days week-1, with running time and speed
      gradually increased from 30 min at 19 m min-1 during the first week to 80 min at
      26 m min-1 during the final training week. The animals of the control group were
      placed on the treadmill twice a week, and received a total of four 'adaptation
      sessions', in which they exercised 15-45 min at 26 m min-1. Brain dialysates were
      analysed with microbore liquid chromatography (LC), with electrochemical
      detection (monoamines and GABA) and fluorescence detection (GLU). Soleus citrate
      synthase and basal striatal concentrations of DA, NA and GLU were significantly
      different between the trained and control animals. Sixty minutes of exercise
      significantly increased extracellular DA, NA and GLU levels in both groups, but
      there was no statistically significant difference in the exercise-induced
      increase between trained and control animals. There was no statistical difference
      in basal or exercise-induced GABA levels between trained and control animals. The
      results indicate that exercise training appears to result in diminished basal
      activity of striatal neurotransmitters, while maintaining the necessary
      sensitivity for responses to acute exercise.

PMID- 9146756
TI  - The effects of allopregnanolone, pregnenolone sulphate and pregnenolone on the
      CA1 population spike of the rat hippocampus after 17 beta-oestradiol priming.

PMID- 9146757
TI  - Nitric oxide from the human respiratory tract efficiently quantified by
      standardized single breath measurements.

PMID- 9146758
TI  - Review article: critical review of meta-analyses of randomized clinical trials in
      hepatogastroenterology.
AB  - BACKGROUND: This review attempts to identify meta-analyses performed in
      hepatogastroenterology, and to assess their quality and to identify simple
      criteria of good quality. METHODS: Meta-analyses of randomized clinical trials in
      hepatogastroenterology published as full papers before 1993 were included. A
      quality score was defined as the sum of 27 items evaluated in each publication
      and coded 2 if adequate, 1 if partial and 0 if missing. Quality criteria were
      identified by discriminant analysis through three groups of meta-analyses defined
      by their quality score (poor, middle, high). RESULTS: From 1981 to 1992, 62
      publications were identified, including 42% in the last 2 years. Nineteen per
      cent concerned peptic ulcers, 18% oesophageal varices and 6% digestive cancers.
      They reported 180 meta-analyses. The quality score ranged from 14 to 40, the
      median was 29. Twenty-five per cent of the studies obtained a score lower than 23
      and 25% a score higher than 34. Several stages of meta-analysis were poorly
      performed: identification and selection of trials, study of trial quality, data
      extraction and achievement of sensitivity analyses, subgroup and indirect
      analyses. Some of them led to biases and questions about the validity of results.
      Five criteria were significantly associated with high quality: presence of a
      protocol, assessment of trial quality, only randomized trials pooled, achievement
      of sensitivity analyses, and peer-reviewed publication. CONCLUSIONS: In
      hepatogastroenterology, there is an exponential increase in publication of meta
      analyses but their quality is heterogeneous. In particular, the control of the
      biases has to be better performed.

PMID- 9146759
TI  - Review article: COX-II inhibitors--a new generation of safer NSAIDs?
AB  - A hundred years after the introduction of aspirin as the first effective anti
      inflammatory drug, problems of tolerability still beset this class of drugs, in
      particular, gastrointestinal toxicity. Despite this, NSAIDs are among the most
      widely used and prescribed drugs world-wide. Many agents have been used to
      counteract these side-effects with varying degrees of success and acceptance.
      Although the central mechanism of NSAID action, reduced prostaglandin production
      by cyclooxygenase (COX) inhibition, was first described 25 years ago, the recent
      discovery of a second, inducible form of cyclooxygenase, COX-2, has stimulated
      research and interest in producing NSAIDs that are inherently safer whilst
      maintaining efficacy. Specific COX-2 inhibitors, the first of which has recently
      been marketed in the UK, offer real hope as safer NSAIDs and this may be realised
      when drugs with even greater specificity become available. However, long-term
      safety and efficacy need to be demonstrated in clinical practice, and questions
      remain unanswered about possible physiological roles for COX-2. Other approaches
      to improving the safety of NSAIDs, including profound acid suppression and nitric
      oxide donation, may prove to be as successful in this rapidly changing field.

PMID- 9146760
TI  - Review article: platelets in inflammatory bowel disease--pathogenetic role and
      therapeutic implications.
AB  - An elevated platelet count is well recognized as a marker of inflammatory bowel
      disease activity. There is an increased incidence of systemic thromboembolism in
      this disease. Recent work indicates that platelets exhibit several
      proinflammatory properties including release of inflammatory mediators, and
      recruitment, chemotaxis and modulation of the activity of other inflammatory
      cells. Furthermore there is evidence that microvascular thrombosis and a
      procoagulant state may play a role in the pathogenesis of inflammatory bowel
      disease. These observations prompted recent studies of platelet activity in
      inflammatory bowel disease, which indicate enhanced platelet aggregation in vivo
      and in vitro, and increased platelet activation as measured by increased release
      of intracellular proteins into plasma and expression of platelet surface markers,
      including P-selectin and GP53. These abnormalities could contribute to the
      pathogenesis of inflammatory bowel disease by enhancing inflammation and
      promoting microinfarction. Aminosalicylates reduce platelet activity although
      they also have many other additional properties to explain their efficacy in
      inflammatory bowel disease. There are however several specific antiplatelet drugs
      now available which may provide new therapeutic possibilities in the management
      of this disease.

PMID- 9146761
TI  - Review article: controversy in the therapy of gastro-oesophageal reflux disease-
      long-term proton pump inhibition or laparoscopic anti-reflux surgery?
AB  - The treatment of gastro-oesophageal reflux disease is controversial. Whilst
      medical treatment is successful in patients with mild to moderate disease, the
      threshold of severity above which an operation should be contemplated remains a
      matter for debate. Laparoscopic anti-reflux surgery may be lowering this
      threshold, as this form of therapy provides several advantages over its open
      counterpart, but it is not without risk, and few long-term results are available.
      This article reviews treatment options for reflux disease and examines the
      relative position of current medical and surgical therapies.

PMID- 9146762
TI  - Review article: update on the role of transjugular intrahepatic portosystemic
      stent-shunt (TIPSS) in the management of complications of portal hypertension.
AB  - In the 8 years since its introduction into clinical practice, initial enthusiasm
      for the transjugular intrahepatic portosystemic stent-shunt (TIPSS) has been
      tempered by a more critical appraisal of its role in the management of portal
      hypertension. TIPSS has established its role as a rescue procedure for variceal
      haemorrhage uncontrolled by endoscopic means and as a treatment for ectopic or
      recurrent variceal bleeding. Randomized trials comparing TIPSS with endoscopic
      methods in the secondary prophylaxis of oesophageal variceal haemorrhage have
      shown reduced rebleeding after TIPSS but no effect on survival. Its exact role in
      this situation awaits further assessment, including quality of life and cost
      analyses, and consideration of the current limited availability of the technique.
      Experience of TIPSS in patients with refractory ascites or hepatorenal syndrome
      has been disappointing. Little data currently exist, but results of further
      randomized studies comparing TIPSS with paracentesis for refractory ascites are
      awaited. Ideally these should be multicentre studies, and should include quality
      of life data for this poor prognostic group. Development of shunt insufficiency
      remains a major problem and occurs in approximately 50% patients at 1 year. The
      need for continued shunt surveillance by Doppler sonography and direct
      portography is the major limitation of TIPSS, but hopefully the development of
      covered stents will address this problem.

PMID- 9146763
TI  - Clinical economics review: Helicobacter pylori-associated peptic ulcer disease.
AB  - The high prevalence and chronic nature of peptic ulcer disease have traditionally
      resulted in a major economic burden on health care systems. In 1991, for example,
      peptic ulcer disease was estimated to account for over one-third of all National
      Health Service expenditure on gastrointestinal diseases. It is now well
      established that elimination of Helicobacter pylori can lead to a dramatic
      reduction in gastroduodenal ulcer relapse, with obvious clinical benefits. This
      review considers the economic implications of the use of H. pylori eradication
      therapy in peptic ulcer disease.

PMID- 9146764
TI  - Emergency admissions for upper gastrointestinal disease and their relation to
      NSAID use.
AB  - BACKGROUND: There are considerable variations in estimates of the number of
      emergency upper gastrointestinal admissions per annum which are attributable to
      nonsteroidal anti-inflammatory drug (NSAID) use. AIM: To obtain a more accurate
      estimate of the number of these emergency admissions per annum in UK. METHODS: A
      retrospective survey of the case notes of all emergency admissions for upper
      gastrointestinal disease ('Cases') to two English District General Hospitals with
      a combined catchment population of 550,000. Records of all community deaths
      attributed to upper gastrointestinal diagnoses (with the same ICD codes) were
      also surveyed. Matched controls were identified from emergency admissions not
      caused by upper gastrointestinal diagnoses. The proportions of patients taking
      NSAIDs on admission to hospital (or at the time of death at home) and the outcome
      following admission to hospital were analysed. RESULTS: 620 emergency upper
      gastrointestinal admissions were identified and matched with 460 controls. Cases
      were more likely to be NSAID users than Controls (31% vs. 16%, OR 2.4, 95% CI:
      1.8, 3.3: P < 0.001). Case NSAID use was higher in females and with increasing
      age. As severity of mode of presentation worsened, the probability of NSAID use
      increased (e.g. OR relative to controls for peptic pain 1.9, for perforation
      5.9). Blood transfusion requirements were significantly higher (P < 0.0001) in
      Cases taking NSAIDs, although NSAID use did not influence mortality.
      Extrapolation from these data indicate that there are 65,000 emergency upper
      gastrointestinal admissions per annum in UK; 12,000 of these admissions
      (including 2230 deaths) are attributable to NSAID use. A further 330 attributable
      deaths occur in the community. CONCLUSIONS: There is a strong association between
      NSAID use and propensity for upper gastrointestinal emergency admission; NSAID
      use is associated with significant morbidity and mortality each year in UK.

PMID- 9146765
TI  - Prescribing of nonsteroidal anti-inflammatory drugs in general practice:
      determinants and consequences.
AB  - AIM: To use Prescribing Analysis and Costs data to investigate factors associated
      with differences in rates of nonsteroidal anti-inflammatory drug prescribing in
      Nottingham general practices. RESULTS: Poisson regression analysis revealed that
      the Age. Sex and Temporary Resident Prescribing Unit Index was the largest
      identifiable influence; larger practice size and a higher index of deprivation
      were also significantly associated with lower prescribing, whilst the number of
      partners was associated with higher levels of prescribing. However, even after
      correcting for the influence of age, sex and temporary residents, there was an
      5.9-fold variation in rates of prescribing. A similar Poisson regression analysis
      to identify factors associated with admission to hospital with ulcer bleeding in
      the elderly over the preceding 57 months identified the rate of nonsteroidal anti
      inflammatory drug (NSAID) prescribing as the only significant influence.
      CONCLUSION: The data are compatible with 1 hospital admission per 2823 NSAID
      prescriptions (95% confidence intervals 2098-8110) and they emphasize the need
      for strategies to reduce levels of NSAID prescribing.

PMID- 9146766
TI  - Helicobacter pylori serology and the management of young dyspeptics: a UK survey
      of gastroenterologists and general practitioners with an interest in
      gastroenterology.
AB  - AIM: To survey the current use of Helicobacter pylori serology for pre-endoscopy
      screening and management of young dyspeptics amongst gastroenterologists and
      general practitioners with an interest in gastroenterology in the United Kingdom.
      METHODS: A postal questionnaire was sent to 536 members of the British Society of
      Gastroenterology and 164 members of the Primary Care Society in Gastroenterology.
      RESULTS: Of those who responded (66%), 25% of general practitioners and 17% of
      gastroenterologists were using H. pylori serology as a screening test for young
      dyspeptics. General practitioners and gastroenterologists differed in their use
      of serology to guide management strategies (P < 0.0003): general practitioners
      eradicate infection from sero-positive patients prior to endoscopy (92%), whilst
      the majority of gastroenterologists endoscope sero-positive patients before
      treatment (55%). More gastroenterologists (89%) would re-test all or selected
      patients to assess eradication compared to general practitioners (45%). 106
      different drug regimes were being used as first line treatment. CONCLUSIONS: H.
      pylori serology as a pre-endoscopy screening test for young dyspeptic patients
      was used by only a fifth of respondents. There were wide variations in attitudes
      and practice in the way H. pylori serology was used in the management of young
      dyspeptics. Trials comparing clinical outcome and cost-effectiveness of different
      serology-based strategies are needed.

PMID- 9146767
TI  - One-week triple therapy with omeprazole, amoxycillin and tinidazole for
      Helicobacter pylori infection: the significance of imidazole resistance.
AB  - BACKGROUND: Triple therapy involving a proton pump inhibitor and two antibiotics
      has been suggested as an effective treatment for Helicobacter pylori infection.
      The impact of imidazole resistance on the efficacy of such regimens is largely
      unknown. METHODS: One hundred patients with culture proven H. pylori infection
      were treated with omeprazole 40 mg b.d., amoxycillin 1000 mg b.d., and tinidazole
      500 mg b.d. for one week. Pre-treatment imidazole susceptibility was measured by
      disk diffusion. Resistance was confirmed by E-test. Eradication was assessed by
      endoscopy 6-8 weeks after the end of treatment. In cases of doubt a 13C-urea
      breath test was performed. Side-effects were scored using a semiquantitative
      scale. RESULTS: H. pylori was eradicated in 95% of the patients with an imidazole
      susceptible strain and in 69% of the patients with a resistant strain (P <
      0.005). Significant side-effects were seen in 12%. CONCLUSION: This proton pump
      inhibitor triple therapy is a simple, reasonably effective regimen with few
      significant side-effects. The efficacy is dependent on the susceptibility of the
      infecting H. pylori strain.

PMID- 9146768
TI  - Immediate repeat course of amoxycillin, metronidazole and omeprazole to eradicate
      Helicobacter pylori.
AB  - AIM: To investigate a repeat treatment regimen with the same antibiotic
      combination of amoxycillin and metronidazole in patients with continuing
      Helicobacter pylori infection. METHODS: Eighty-two patients with severe peptic
      ulcer disease and concurrent Helicobacter pylori infection were treated with a
      two week regimen of omeprazole (40 mg once daily), amoxycillin (750 mg t.d.s.)
      and metronidazole (400 mg t.d.s.). Upper gastrointestinal tract endoscopy was
      performed before, and approximately 2 months after, completion of antibiotic
      therapy. Biopsies were taken for rapid urease testing and the histological
      demonstration of H. pylori infection. Patients with persistent H. pylori
      infection at follow-up endoscopy were re-treated with a second and identical
      antibiotic treatment course. A subsequent endoscopic examination with
      accompanying biopsies was performed at least 6 weeks after the second treatment
      course and after a further 6, 18 and 30 months. RESULTS: Eradication of H. pylori
      was achieved in 69 patients (84%, 95% CI: 75-90%) after the first treatment. Four
      patients (4/82 = 5%) were withdrawn from the study because of side-effects. All
      of the remaining nine patients had their H. pylori infection eradicated after the
      second treatment course (95% CI: 70-100%). Seventy-eight patients had a follow-up
      examination after a median 30 months of the initial eradication of H. pylori, and
      all but one remained free of infection and none had an ulcer relapse.
      CONCLUSIONS: This study demonstrates that patients with persistent H. pylori
      infection after completing a primary course of omeprazole (40 mg once daily),
      amoxycillin (750 mg t.d.s.) and metronidazole (400 mg t.d.s.) will probably
      respond to a repeat course of treatment with the same antibiotic combination.

PMID- 9146769
TI  - Randomized study comparing omeprazole plus amoxycillin versus omeprazole plus
      clarithromycin for eradication of Helicobacter pylori.
AB  - BACKGROUND: Dual therapy with omeprazole plus amoxycillin or with omeprazole plus
      clarithromycin has been proposed for eradication of Helicobacter pylori. The main
      problem is the great variability in the rate of eradication. METHODS: A group of
      287 consecutive patients with active peptic ulcers and H. pylori infections were
      admitted to a prospective, randomized, multicentre study, to be given omeprazole
      20 mg b.d. plus either amoxycillin 1 g b.d. or clarithromycin 500 mg t.d.s. for 2
      weeks. Cure was defined as the absence of H. pylori infection, 4-6 weeks after
      completing anti-microbial therapy, assessed by urease activity and histology of
      antral and body gastric biopsies. RESULTS: The bacteria were eradicated in 68/143
      patients (48%) treated with amoxycillin and omeprazole and 70/144 patients (49%)
      treated with clarithromycin and omeprazole (intention-to-treat analysis). The
      ulcers were healed in 118/127 patients (93%) treated with amoxycillin and in
      115/123 (94%) of those treated with clarithromycin. Undesirable effects were rare
      with both treatments. CONCLUSIONS: Combined treatment with omeprazole plus either
      amoxycillin or clarithromycin produced a high percentage of short-term healing of
      ulcers and was well tolerated, but is not useful as first-line anti-Helicobacter
      pylori treatment.

PMID- 9146770
TI  - An increasing dose of omeprazole combined with amoxycillin cures Helicobacter
      pylori infection more effectively.
AB  - BACKGROUND: The combination of omeprazole and amoxycillin has demonstrated
      effectiveness with very few side-effects in the treatment of H. pylori infection,
      however cure rates have varied widely. The present study addresses the question
      as to the extent to which the cure rate of H. pylori infection depends on the
      size of the daily omeprazole dose, and investigates other patient-related factors
      that influence treatment success. METHODS: In a randomized, controlled and
      investigator-blinded trial, 163 hospitalized patients with H. pylori-associated
      gastritis were treated with 20 mg omeprazole once daily in the morning, 20 mg
      omeprazole b.d., 40 mg omeprazole b.d. or 60 mg omeprazole b.d. for 14 days. In
      addition, all patients received 1000 mg amoxycillin b.d. on days 5-14. Endoscopic
      and histological examinations were performed prior to treatment, at the end of
      treatment and 4 weeks after completion of treatment. RESULTS: H. pylori infection
      was cured in 18 of 40 (45%, 95% CI: 29-62%), in 22 of 39 (56.4%, 95% CI: 40-72%),
      in 25 of 38 (65.8%, 95% CI: 49-80%), and in 33 of 40 (82.5%, 95% CI: 67-93%)
      patients, respectively, (P < 0.001). Side-effects leading to discontinuation of
      treatment occurred in only 1.2%. CONCLUSION: The daily dose of omeprazole is an
      important factor for the success of dual therapy comprising omeprazole and
      amoxycillin in curing H. pylori infection. Cure of H. pylori infection correlates
      positively and significantly with the size of the daily omeprazole dose. The
      combination of high-dose omeprazole and amoxycillin is an effective and well
      tolerated regimen for the treatment of H. pylori-associated diseases.

PMID- 9146771
TI  - Recurrence of duodenal ulcer after Helicobacter pylori eradication is related to
      high acid output.
AB  - BACKGROUND: Helicobacter pylori eradication reduces the recurrence of duodenal
      ulcers. It is unclear why duodenal ulcers rarely recur in the absence of
      reinfection with H. pylori or NSAID treatment. METHODS: Basal, gastrin-releasing
      peptide- and pentagastrin-stimulated peak acid outputs in patients with ulcer
      relapse after H. pylori eradication were measured, and compared with patients
      without ulcer relapse after H. pylori eradication. RESULTS: Pentagastrin
      stimulated peak acid output was significantly higher in H. pylori-positive
      patients with duodenal ulcers than in H. pylori-negative controls, and fell
      significantly after H. pylori eradication. In H. pylori-negative patients with
      recurrent duodenal ulcers, pentagastrin-stimulated peak acid output was
      significantly higher than in controls and similar to H. pylori-positive patients
      with duodenal ulcers. CONCLUSIONS: These findings suggest that duodenal ulcer
      relapse after eradication of H. pylori may be related to high pentagastrin
      stimulated peak acid output. In this subset of patients with duodenal ulcers,
      maintenance anti-secretory treatment may be necessary to prevent relapse.

PMID- 9146772
TI  - Efficacy and tolerance of mesalazine suppositories vs. hydrocortisone foam in
      proctitis.
AB  - BACKGROUND: Topical treatments with steroids or mesalazine are the most effective
      treatments for idiopathic proctitis. AIM: To compare the efficacy and tolerance
      of mesalazine suppositories vs. hydrocortisone acetate foam in the treatment of
      acute proctitis. PATIENTS AND METHODS: 242 patients with active idiopathic
      proctitis were randomized to receive once daily either one Pentasa suppository
      (mesalazine 1 g) or 100 mg hydrocortisone (Colofoam) for 14-21 days (until
      remission). Disease activity and tolerance of the treatments were assessed using
      a daily questionnaire, by physician assessment, and endoscopy score. RESULTS:
      Both treatments induced a significant reduction in disease activity. Mesalazine
      suppositories were significantly more effective than hydrocortisone on rectal
      blood loss (P = 0.002) and mucus (P = 0.02) parameters, and on the degree of the
      decrease in endoscopy score (P = 0.02). No significant difference was observed
      between treatments concerning histology or tolerance. CONCLUSION: Mesalazine
      suppositories were as well-tolerated as hydrocortisone foam, but were more
      effective for some parameters of disease activity.

PMID- 9146773
TI  - Anti-thyroid drugs decrease mucosal damage in a rat model of experimental
      colitis.
AB  - BACKGROUND: Methimazole, an anti-thyroid drug, was recently found to be useful in
      the treatment of systemic lupus erythematosus and other autoimmune diseases.
      Moreover, decreased thyroid hormone production is associated with a variety of
      immunological manifestations, such as reduced activation of CD4+ cells, increased
      CD8+ cell activity and reduced soluble IL-2 receptors. In the present study we
      examined the effects of methimazole and propylthiouracil on a rat model of
      experimental colitis. METHODS: Colitis was induced by intracolonic administration
      of 30 mg trinitrobenzene sulphonic acid (TNB). Two weeks prior to induction of
      colitis, rats were treated by either methimaziole (0.04%) or propylthiouracil
      (0.01%) in drinking water after a week of free access to water. Rats were
      sacrificed 48 h or 7 days after induction of colitis. The colon was isolated,
      rinsed with ice-cold water and weighed. Damage was assessed both macroscopically
      and microscopically and myeloperoxidase (MPO) activity determined. RESULTS: All
      treated rats were hypothyroid as manifested by a significant elevation of thyroid
      stimulating hormone (TSH), by comparison with the control groups (mean -1.82 +/-
      0.40 versus 0.11 +/- 0.02 mmol/L, respectively). The inflammatory response
      elicited by TNB resulted in severe mucosal damage 48 h after damage induction,
      which persisted for 7 days. Pre-treatment with either methimazole 0.04% or
      propylthiouracil 0.01% significantly decreased mucosal damage macroscopically
      (lesion area, lesion score and segmental weight) microscopically and also
      significantly decreased MPO level at both time points (P < 0.01). CONCLUSIONS:
      Methimazole and propylthiouracil significantly reduce mucosal damage and colonic
      weight in a rat model of colitis. The mode by which they do so remains to be
      studied.

PMID- 9146774
TI  - Suppression of intestinal mucosal natural killer cells by corticosteroids.
AB  - BACKGROUND: Corticosteroid therapy of patients with inflammatory bowel disease
      can give rise to systemic side-effects. Budesonide is a topically acting
      corticosteroid with low systemic bioavailability and is efficacious in the
      treatment of inflammatory bowel disease. Natural killer cells were previously
      found to be altered, both systemically and locally, in patients with inflammatory
      bowel disease. Modulatory effects of budesonide, prednisolone, dexamethasone, and
      cortisol on peripheral blood NK cells have already been described, but have never
      been assessed on mucosal NK cells from the intestine. METHODS: The effect of the
      synthetic corticosteroids prednisolone and budesonide, the endogenous
      corticosteroid cortisol, and adrenocorticotropic hormone was analysed on NK cells
      isolated from the lamina propria of human intestinal resection specimens.
      RESULTS: The three corticosteroids suppressed intestinal NK cell activity, not
      only during the cytotoxicity assay, but also after pre-incubation of the lamina
      propria mononuclear cells. ACTH, however, did not affect the activity of
      intestinal NK cells. We previously showed that corticosteroid-suppressed
      peripheral blood NK cell activity could be restored in vivo, but not in vitro, by
      the administration of ACTH. In the present study, the in vitro incubation of
      budesonide- or prednisolone-suppressed mucosal NK cells with cortisol, alone or
      combined with ACTH, did not revert the suppressed NK cell activity. These
      findings are similar to our previous observations with peripheral blood NK cells.
      CONCLUSIONS: Intestinal mucosal NK cells can be suppressed by systemically as
      well as locally acting corticosteroids. This suppression in NK cell activity is
      not reversed by incubation with cortisol and/or ACTH.

PMID- 9146775
TI  - In single doses ranitidine effervescent is more effective than lansoprazole in
      decreasing gastric acidity.
AB  - BACKGROUND: A rapid and reproducible decrease of gastric acidity is preferable in
      patients with penetrating/perforating peptic ulcers and in on-demand treatment of
      some patients with dyspepsia. The present study was done to compare the effect of
      single doses of ranitidine effervescent with that of the proton pump inhibitor
      lansoprazole. METHOD: Twelve healthy young volunteers were studied by 11-h
      intragastric continuous pH recording after the intake of ranitidine 150 or 300 mg
      effervescent tablets or lansoprazole 30 mg capsules. Trial medications were taken
      with 200 mL water, and the subjects remained fasting apart from 250 mL fluid at 4
      h. RESULTS: Ranitidine effervescent, both 150 and 300 mg, induced a rapid and
      persisting increase in gastric pH in most of the subjects, whereas a single dose
      of lansoprazole 30 mg did not affect intragastric pH in five of the twelve
      subjects. CONCLUSION: The histamine H2-blocker ranitidine given as an
      effervescent formulation is superior to the proton pump inhibitor lansoprazole in
      inducing a rapid decrease of gastric acidity.

PMID- 9146776
TI  - Lansoprazole versus omeprazole: influence on meal-stimulated gastric acid
      secretion.
AB  - AIMS: To investigate, by means of meal-stimulated acid secretion, the extent to
      which differences in plasma half-life, bioavailability and the recommended
      therapeutic dose can influence the antisecretory potency of lansoprazole and
      omeprazole. METHODS: In this double-blind, placebo-controlled, crossover study,
      10 healthy male volunteers received 15 mg or 30 mg lansoprazole, 20 mg or 40 mg
      omeprazole or placebo for 5 days, in a randomized order. Meal-stimulated acid
      secretion was determined by means of a homogenized test meal and intragastric
      titration. RESULTS: On day 1, meal-stimulated acid secretion was decreased by 35%
      and 45% after administration of 15 mg or 30 mg lansoprazole, and by 16% and 42%
      after 20 mg or 40 mg omeprazole. After 3 and 5 days of dosing the decreases were
      53% and 48% with 15 mg lansoprazole, 82% and 82% with 30 mg lansoprazole, 43% and
      39% with 20 mg omeprazole, and 76% and 83% with 40 mg omeprazole. At all
      measuring points during the 5-day dosing periods, lansoprazole 15 mg and 30 mg
      proved superior to 20 mg omeprazole in inhibiting meal-stimulated gastric acid
      secretion, but the differences were only statistically significant for the
      lansoprazole 30 mg dose, 30 mg lansoprazole and 40 mg omeprazole proved
      equipotent. On day 1 only 30 mg lansoprazole was significantly better than
      placebo. CONCLUSION: This study demonstrated the following order of antisecretory
      potency: 30 mg lansoprazole = 40 mg omeprazole > 15 mg lansoprazole approximately
      20 mg omeprazole.

PMID- 9146777
TI  - Lansoprazole 15 and 30 mg daily in maintaining healing and symptom relief in
      patients with reflux oesophagitis.
AB  - BACKGROUND: In patients with reflux oesophagitis, endoscopic healing and symptom
      relief are considered important treatment goals in long-term care. AIM: To
      compare the effect of lansoprazole 15 and 30 mg daily on maintaining endoscopic
      healing and symptom relief in patients with moderate reflux oesophagitis.
      PATIENTS AND METHODS: In a single-centre, double-blind randomized clinical trial,
      103 patients with grade 1 or 2 reflux oesophagitis who were endoscopically healed
      and asymptomatic after lansoprazole 30 mg daily for 12 weeks, were randomized to
      maintenance therapy with either lansoprazole 15 mg or 30 mg o.m. Endoscopy was
      repeated after 3, 6 and 12 months, and symptom relief assessed after 3, 6, 9 and
      12 months. Relapse of oesophagitis or symptoms were considered end-points.
      RESULTS: After 12 months, 14/50 patients (28%) receiving lansoprazole 15 mg daily
      had suffered an endoscopic relapse compared to 8/53 patients (15%) treated with
      lansoprazole 30 mg daily. A life table analysis showed no statistically
      significant difference between the two groups (P = 0.086). Significantly more
      patients were kept in complete symptomatic remission in the 30 mg group (P <
      0.01). In the 15 mg group, 23/50 (46%) had suffered either an endoscopic or
      symptomatic relapse on completion of the study, compared to 12/53 (23%) in the 30
      mg group. A life table analysis showed this difference to be statistically
      significant (P = 0.010). Lansoprazole 15 and 30 mg daily were equally well
      tolerated. CONCLUSION: No statistically significant differences were found in
      endoscopic relapse rate or occurrence of adverse events, while lansoprazole 30 mg
      proved superior to 15 mg in maintaining patients in symptomatic relief and
      combined endoscopic and symptomatic remission.

PMID- 9146778
TI  - Daily omeprazole surpasses intermittent dosing in preventing relapse of
      oesophagitis: a US multi-centre double-blind study.
AB  - INTRODUCTION: Relapse of erosive oesophagitis occurs in almost all patients if
      treatment is stopped after initial healing. AIM: To assess the potential of
      different therapeutic regimens of omeprazole to prevent relapse of erosive reflux
      oesophagitis after initial healing with omeprazole. PATIENTS AND METHODS:
      Patients whose active erosive reflux oesophagitis (grade > or = 2) had healed
      (grade 0 or 1) after 4-8 weeks of open-label omeprazole 40 mg daily (phase I)
      were eligible to join a multi-centre, 6-month double-blind, placebo-controlled
      maintenance study (phase II), which included endoscopy, symptom assessments,
      serum gastrin measurements, and gastric fundic biopsies. During phase I,
      endoscopy was performed at weeks 0, 4, and 8. At the end of phase I, 429 of 472
      patients (91%) were healed, and there were significant reductions in heartburn,
      dysphagia and acid regurgitation. Of the 429 patients who healed, 406 joined
      phase II and were randomized to one of three groups: 20 mg omeprazole daily (n =
      138), 20 mg omeprazole for 3 consecutive days each week (n = 137), or placebo (n
      = 131). During phase II, endoscopy was performed at months 1, 3, and 6 or at
      symptomatic relapse. RESULTS: The percentages of patients still in endoscopic
      remission at 6 months were 11% for placebo, 34% for omeprazole 3-days-a-week, and
      70% for omeprazole daily. Both omeprazole regimens were superior to placebo in
      preventing recurrence of symptoms (P < 0.001); however, omeprazole 20 mg daily
      was superior to omeprazole 20 mg 3-days-a-week (P < 0.001). Compared to baseline,
      omeprazole therapy resulted in no significant differences among treatment groups
      in the distribution of gastric endocrine cells. CONCLUSIONS: These results show
      that after healing of erosive oesophagitis with 4-8 weeks of omeprazole, relapse
      of oesophagitis and recurrence of reflux symptoms can be prevented in 70% of
      patients with a maintenance regimen of 20 mg daily, but that intermittent dosing
      comprising 3 consecutive days each week significantly compromises efficacy.

PMID- 9146779
TI  - The effect of intravenous erythromycin on solid meal gastric emptying in patients
      with chronic symptomatic post-vagotomy-antrectomy gastroparesis.
AB  - BACKGROUND: Chronic symptomatic gastroparesis occurs in 3-5% of patients
      following vagotomy and antrectomy. Erythromycin, a macrolide antibiotic, improves
      gastric emptying in patients with idiopathic and diabetic gastroparesis.
      Erythromycin's effect on gastric emptying in patients with post-vagotomy
      antrectomy gastroparesis is unknown. The aim of this study was to determine if a
      single dose of intravenous erythromycin (1 mg/kg or 6 mg/kg) accelerates solid
      meal gastric emptying in patients with chronic symptomatic post-vagotomy
      antrectomy gastroparesis. METHODS: Six patients were entered into the study,
      three males and three females, with a mean age of 50 years. Four patients were
      randomized to receive erythromycin 6 mg/kg and two patients 1 mg/kg. The mean
      time since initial surgery was 9.2 years (range 1-16 years) with five patients
      having undergone a Roux-en-Y revision. RESULTS: Intravenous erythromycin
      significantly lowered percentage gastric retention at 120 min, from a baseline of
      90.5 +/- 6% (S.E.M.) to 40.1 +/- 4.8% after erythromycin (P = 0.0002).
      Erythromycin improved gastric emptying in each patient by at least 40%.
      Intravenous erythromycin significantly accelerated the rate of gastric emptying
      in the first 30 min after meal ingestion from a baseline rate of 0.072 +/-
      0.06%/min to 0.96 +/- 0.31%/min after erythromycin (P = 0.028). For each of the
      subsequent 30 minute time periods, erythromycin had no significant effect on the
      rate of gastric emptying. CONCLUSION: Intravenous erythromycin significantly
      improves the initial phase of solid meal gastric emptying in patients with
      chronic symptomatic post-antrectomy-vagotomy gastroparesis.

PMID- 9146780
TI  - Double-blind study of the effect of cisapride on constipation and abdominal
      discomfort as components of the irritable bowel syndrome.
AB  - AIM: To study the effect of prokinetic treatment with cisapride in patients with
      constipation-predominant irritable bowel syndrome. PATIENTS AND METHODS: Ninety
      six patients were randomly assigned to treatment with either cisapride 5 mg three
      times daily or placebo three times daily for a period of 12 weeks. The dosage
      could be doubled after 4 weeks. Presence of the target symptoms abdominal pain,
      constipation and abdominal bloating was an obligatory criterion for inclusion in
      the study. RESULTS: After 12 weeks of treatment, 31%, 56% and 27% of the
      cisapride treated patients were found to be without the three target symptoms (P
      < 0.05). The corresponding percentages for the placebo-treated patients were 31%,
      58% and 19%, respectively, (P < 0.05). The visual analogue scale (VAS) symptom
      scores assessed by the patients for global rating of bowel disease, general well
      being and frequency of stool passage improved significantly within each treatment
      group (P < 0.05). Evaluation of efficacy parameters using intention-to-treat
      analysis showed no statistically significant differences between the groups.
      Using efficacy analysis, the difficulty of stool passage showed a significantly
      higher improvement with cisapride (P < or = 0.05). CONCLUSIONS: These results
      indicate that cisapride is not superior to placebo in the treatment of
      constipation and abdominal discomfort as components of irritable bowel syndrome.
      It may, however, be of use in improving the difficulty of stool passage.

PMID- 9146781
TI  - The irritable bowel severity scoring system: a simple method of monitoring
      irritable bowel syndrome and its progress.
AB  - BACKGROUND: The clinical assessment and investigation of irritable bowel syndrome
      would be greatly facilitated by the introduction of a simple, easy to use
      severity scoring system. Such a system, developed in our department over a number
      of years, has been submitted to validation in a total of 141 patients and 40
      healthy controls. METHODS: The system, incorporating pain, distension, bowel
      dysfunction and quality of life/global well-being, was assessed for its ability
      to reliably score patients previously classified as mild, moderate or severe. The
      reproducibility and sensitivity to change of the system was also assessed.
      RESULTS: The maximum achievable score was 500. Mild, moderate and severe cases
      were indicated by scores of 75 to 175, 175 to 300 and > 300 respectively.
      Controls scored below 75 and patients scoring in this range can be considered to
      be in remission. There was a highly significant difference between controls and
      patients as a whole (P = 0.0001) as well as significant differences (P < 0.01)
      between all severity categories. Scores repeated within 24 h were very
      reproducible and sensitivity to change was also extremely good (P < 0.001) with a
      change of 50 reliably indicating improvement. CONCLUSION: These results suggest
      that this scoring system should prove to be a valuable instrument in helping to
      meet the many challenges offered by irritable bowel syndrome.

PMID- 9146782
TI  - Effect of oral pancreatic enzyme administration on digestive function in healthy
      subjects: comparison between two enzyme preparations.
AB  - BACKGROUND: Intraduodenal proteases exert a negative feedback on pancreatic
      secretion. AIM: To investigate the effect of two pancreatic enzyme preparations
      (enteric-coated tablets, and capsules with enteric-coated microtablets) on
      postprandial pancreatic and bile acid secretion, gastroduodenal motility and
      release of gastrin and pancreatic polypeptide in healthy humans. METHODS: Twenty
      healthy males were studied on two different days one week apart. After an
      overnight fast a nine-lumen motility tube was positioned with the distal tip at
      the Treitz angle. On each study day, 30 min after an interdigestive migrating
      motor complex-phase III, a semi-liquid test meal was given either alone (n = 20)
      or with enzymes (3 tablets (n = 10) or 2 capsules with microtablets (n = 10);
      40,000 U lipase and 2000 proteases) in a randomized order, and the study
      continued over 2 h. Motility was continuously recorded with four ports in the
      antrum and three in the duodenum, using a low-compliance pneumohydraulic
      perfusion system. Secretion of human-specific pancreatic elastase and bile acids
      was measured by a standard duodenal intubation perfusion technique. Plasma
      concentrations of gastrin and pancreatic polypeptide were measured by specific
      radioimmunoassays. RESULTS: Postprandial pancreatic secretion was significantly
      reduced by administration of microtablets (median 82 mg/2 h vs. 70 mg/2 h, P <
      0.02) but not by tablets (median 59 mg/2 h vs. 58 mg/2 h. N.S.). No changes were
      observed in bile acid secretion, antroduodenal motility or release of gastrin and
      pancreatic polypeptide. CONCLUSIONS: Oral administration of pancreatic enzymes at
      normal therapeutic doses significantly inhibits postprandial pancreatic secretion
      in healthy humans, when capsules with enteric-coated microtablets are given.
      Exogenous pancreatic enzymes have no significant effect on bile acid secretion,
      gastroduodenal motility and hormone release.

PMID- 9146783
TI  - Ursodeoxycholic and tauro-ursodeoxycholic acids for the treatment of primary
      biliary cirrhosis: a pilot crossover study.
AB  - BACKGROUND: Results from animal studies and preliminary data from pilot studies
      in patients with primary biliary cirrhosis suggest that tauro-ursodeoxycholic
      acid has metabolic properties that may favour its long-term use as an alternative
      to ursodeoxycholic acid for patients with chronic cholestatic liver diseases. No
      direct comparison of tauro-ursodeoxycholic and ursodeoxycholic acids have yet
      been carried out in primary biliary cirrhosis. METHODS: The effects of
      ursodeoxycholic and tauro-ursodeoxycholic acids were compared in 23 patients with
      primary biliary cirrhosis according to a crossover design. Both drugs were
      administered at the daily dose of 500 mg. in a randomly assigned sequence for two
      6-month periods separated by a 3-month wash-out period. RESULTS: Serum liver
      enzymes related to cholestasis and cytolysis consistently improved, as compared
      to baseline values, during the administration of both ursodeoxycholic and tauro
      ursodeoxycholic acids, but no significant difference between these two bile acids
      was found. Both treatments were well tolerated and no patient complained of side
      effects. CONCLUSION: In the short-term, tauro-ursodeoxycholic acid appears to be
      safe and at least as effective as ursodeoxycholic acid for the treatment of
      primary biliary cirrhosis.

PMID- 9146784
TI  - Acyclovir-induced colitis.
AB  - Three patients developed acute colitis, either de novo, or as an exacerbation of
      pre-existing colitis, following the use of oral acyclovir, prescribed for Herpes
      zoster or Herpes simplex infection. Rechallenge with oral acyclovir was performed
      in one patient, and resulted in a recurrence of colitic symptoms. It is
      speculated that acyclovir can have a direct irritant effect on large bowel
      mucosa.

PMID- 9146785
TI  - Endoscopic methods for the diagnosis of Helicobacter pylori.
AB  - This article reviews endoscopic methods for the diagnosis of Helicobacter pylori.
      At the time of endoscopy certain findings (gastroduodenal ulceration and/or
      antral nodularity) may be highly suggestive of H. pylori infection. Endoscopic
      acquisition of gastric biopsies, however, leads to a definitive diagnosis of
      infection on the basis of both direct and indirect tests. Direct tests include
      culture and histological detection (considered the gold standard). There are a
      variety of stains available for the detection of H. pylori; their choice is
      influenced by local expertise and the clinical situation. If at least three
      biopsies are obtained from non-adjacent gastric sites, incorrect assessment of H.
      pylori status should be rare. Indirect methods utilize the detection of urease.
      The three biopsy rapid urease tests commercially available in the USA have
      similar performance characteristics, except that two are gel tests requiring up
      to 24 h to read, while one is a strip test which is read up to 1 h. Specificity
      is excellent for these tests, while sensitivity is more variable. Rapid urease
      tests are the endoscopic tests of choice for initial evaluation due to their low
      cost.

PMID- 9146786
TI  - Non-endoscopic tests in the diagnosis of Helicobacter pylori infection.
AB  - The urea breath test (UBT) and serological antibody detection are simpler and
      less expensive than endoscopic tests for the diagnosis of Helicobacter pylori.
      For the UBT, either non-radioactive 13C or radioactive 14C is used as an isotopic
      marker. 14C-UBTs are cheaper and are safe, but licensing regulations may make
      them inconvenient. Some UBTs have been simplified by omitting the normal test
      meal and encapsulating the urea to avoid metabolism by oral bacteria. These
      modified test need further validation, especially when used for assessing H.
      pylori status after treatment. Serological tests detect circulating IgG or IgA.
      They are of variable accuracy, the best performing as well as UBTs. Paired serum
      samples pre-treatment and 6 months post-treatment accurately assess treatment
      success. Rapid in-office tests appear less accurate and cannot be used for post
      treatment assessment. In practice, for primary diagnosis of H. pylori infection,
      endoscopic tests are best because endoscopy allows assessment of treatment
      indications. Where indications already exist or taking biopsies is dangerous.
      UBTs or serology are suitable, but serology is cheaper and more convenient. After
      treatment, endoscopy is usually unnecessary and UBTs accurately assess H. pylori
      status at 4 weeks. Serology is an alternative only if results are not required
      before 6 months.

PMID- 9146787
TI  - The role of antisecretory drugs in the treatment of Helicobacter pylori
      infection.
AB  - The efficacy of antibiotics against Helicobacter pylori is enhanced by the co
      administration of antisecretory drugs. While proton pump inhibitors appear to
      have some direct effect on H. pylori and extreme hypochlorhydria has a
      deleterious effect on the organism, the most likely mechanism by which
      antisecretory drugs as a class provide this effect is by improving the efficacy
      of the antibiotics themselves. Although proton pump inhibitors are the most
      widely used antisecretory agents, H2 receptor antagonists also enhance antibiotic
      effects.

PMID- 9146788
TI  - The actions of bismuth in the treatment of Helicobacter pylori infection.
AB  - Bismuth salts have been used in medicine for over three centuries, particularly
      in the treatment of dyspepsia. Commonly used agents include colloidal bismuth
      subcitrate (CBS), bismuth subsalicylate (BSS) and the newer ranitidine bismuth
      citrate (RBC). These are safe drugs which exert local effects on the
      gastroduodenal mucosa. Gastric mucosal levels of bismuth exceed the
      concentrations required to kill Helicobacter pylori in vitro. The mechanisms of
      actions of bismuth on gastrointestinal pathogens including H. pylori are complex
      and include inhibition of protein and cell wall synthesis, membrane function and
      ATP synthesis. Adherence of H. pylori to surface epithelial cells is also
      impaired. Bismuth monotherapy is effective in vivo to suppress H. pylori but cure
      rates are low. CBS, BSS and RBC have synergistic activity with one or two
      antibiotics and are effective in eradicating H. pylori. CBS and RBC also exert
      other effects on the mucosa including cytoprotective and ulcer healing
      properties. In addition, RBC is effective in inhibiting gastric acid secretion.

PMID- 9146789
TI  - The treatment of Helicobacter pylori infection.
AB  - Indications for eradication of Helicobacter pylori infection have widened since
      the National Institutes of Health consensus conference in 1994. It is argued that
      they should now include infected patients with non-ulcer dyspepsia, those
      concerned about the risk of gastric cancer, patients with gastric lymphoma, and
      those requiring long-term treatment with a proton pump inhibitor. Problems with
      existing clinical trials are discussed, and the results of different treatment
      regimens are discussed. It is proposed that future eradication trials should
      investigate H. pylori-infected subjects identified by serology, rather than ulcer
      patients, and that eradication is proved only by a pair of 13C-urea breath tests.

PMID- 9146790
TI  - Resistance of Helicobacter pylori to antibiotics.
AB  - Resistance of Helicobacter pylori to antibiotics included in current regimens
      used to eradicate H. pylori is a major reason for failure. The definition of
      resistance is not simple, and the clinical relevance of in vitro results must be
      considered. The different methods of testing antibiotics cannot apply in all
      cases. Resistance to clarithromycin has a low prevalence rate (< 10%) and its
      mechanism is well defined (point mutation on the 23S rRNA genes, and decreased
      binding of the antibiotics to the ribosome). Its clinical relevance is not
      questioned and, because of a clear occurrence of a bimodal strain population, the
      method for detecting resistance is not crucial. Resistance to nitroimidazoles is
      much more common, probably in the range of 30% or more in Europe. Neither the
      mechanism of action of metronidazole resistance nor its mechanism of is well
      known. The redox potential inside the cell which is important in reducing
      metronidazole to its active metabolite is probably a key element, but the exact
      metabolites involved are not yet known. Metronidazole resistance was found to be
      clinically relevant when standard triple therapy was used. The relevance is
      questioned for triple therapies including a proton pump inhibitor, clarithromycin
      and metronidazole. More clinical data are needed in this field and the use of
      agar dilutions is recommended to assess the susceptibility of H. pylori to
      metronidazole. The mechanism of resistance to quinolones has been described but
      these compounds are not currently used for H. pylori infection. No resistance has
      yet been described for amoxycillin but continuous surveillance is needed in order
      to detect new cases, as was recently the case for tetracycline resistance.

PMID- 9146791
TI  - Reinfection versus recrudescence in Helicobacter pylori infection.
AB  - Antimicrobial treatment of Helicobacter pylori is the proper management strategy
      in patients with ulcers. A high rate of H. pylori reinfection after successful
      eradication therapy however, may give rise to ulcer recurrence. The risk of
      reinfection, depending on the prevalence and the rate of acquisition of H. pylori
      infection, varies with socioeconomic status, age and geographical location. The
      rate of reinfection may vary in a similar way. The available data in the
      literature reveal that reinfection by H. pylori is low or absent in developed
      countries and may be lower than the initial rate of acquisition. In addition,
      reported cases of H. pylori reinfection are often cases of recrudescent H. pylori
      infection. Acquisition rate in developing countries is high, so the reinfection
      rate is expected to be higher than in developed countries. However, studies
      discriminating reinfection from recrudescence are lacking and therefore more data
      from developing regions are needed to settle if 'cured once, cured forever' holds
      true.

PMID- 9146792
TI  - The role of Helicobacter pylori infection in non-ulcer dyspepsia.
AB  - It is currently unclear whether Helicobacter pylori (H. pylori) infection plays a
      role in patients who fulfil the criteria for non-ulcer dyspepsia. This paper
      reviews evidence for H. pylori-induced changes in gastric emptying,
      gastrointestinal motility, gastric acid secretion, and gastric perception in
      patients with non-ulcer dyspepsia. Problems in study design and execution of non
      ulcer dyspepsia treatment trials are discussed. The results of non-ulcer
      dyspepsia treatment trials which have been performed in H. pylori-positive
      patients are reviewed. To date none of them has convincingly shown that cure of
      the H. pylori infection leads to a sustained improvement in symptoms.

PMID- 9146793
TI  - Helicobacter pylori and the risk and management of associated diseases:
      gastritis, ulcer disease, atrophic gastritis and gastric cancer.
AB  - This review addresses the role of H. pylori and the effect of H. pylori
      eradication on gastritis, peptic ulcer disease, atrophic gastritis and gastric
      cancer. Specific emphasis is given to various factors that influence the clinical
      course of this infection. H. pylori induces chronic gastritis in virtually all
      infected subjects. This inflammation can lead to peptic ulceration and atrophic
      gastritis in a considerable number of infected subjects. A minority eventually
      develops gastric cancer. The risk of such complications depends upon the severity
      of gastritis, which is determined by various host- and bacteria-related factors.
      Among bacterial factors, most of the evidence addresses the cagA pathogenicity
      island, the presence of which has been associated with more severe gastritis,
      peptic ulceration, atrophic gastritis and gastric cancer. Among host factors,
      most of the evidence focuses on acid production in response to H. pylori
      infection. An increase in acid secretion limits H. pylori gastritis to the antrum
      at the risk of duodenal ulcer disease; a reduction allows more proximal
      inflammation at the risk of atrophic gastritis, gastric ulcer disease, and
      gastric cancer. Gastritis and atrophy negatively influence acid secretion. H.
      pylori eradication is required in peptic ulcer disease and may be advocated in
      patients on profound acid suppressive therapy; it has been shown to cure
      gastritis and prevent ulcer recurrence. Further study is required to determine
      the efficacy of H. pylori eradication in the primary and secondary prevention of
      atrophic gastritis and gastric cancer.

PMID- 9146794
TI  - Gastric MALT-lymphoma and Helicobacter pylori infection.
AB  - The presence of lymphoid tissue in the gastric mucosa is virtually pathognomonic
      of Helicobacter pylori infection. This lymphoid tissue has mucosa-associated
      lymphoid tissue (MALT) characteristics suggesting that H. pylori infection may
      represent a stimulus for the growth of gastric MALT lymphoma. H. pylori can be
      detected in more than 90% of patients with low-grade gastric MALT lymphoma
      supporting the aetiological role of the organism. The strongest evidence for the
      significance of H. pylori in the pathogenesis of low aetological-grade gastric
      MALT lymphoma is provided by clinical studies showing that cure of H. pylori
      infection is followed by a complete regression of these tumours in most patients.
      This paper reviews the current knowledge about antibacterial treatment of low
      grade gastric MALT lymphoma, and immunological and molecular aspects in the
      pathogenesis of the disease.

PMID- 9146795
TI  - Outcomes research in Helicobacter pylori infection.
AB  - While the medical community has accepted the role of H. pylori in the
      pathogenesis of peptic ulcer disease, confusion persists among clinicians
      regarding when and on which patients to attempt H. pylori eradication. Thus, the
      objective for outcomes research in H. pylori is to help clinicians identify which
      patients benefit from H. pylori eradication and to determine the cost-effective
      strategies for their diagnosis, treatment and follow-up care. Economic evaluation
      of the impact of H. pylori infection has focused primarily on assessment of
      patient with documented peptic ulcer disease, with particular attention to costs
      of pharmaceuticals. However, drug costs are only one portion of the total costs
      of management for patients with acid-related disorders and therefore must be put
      in the appropriate context. Additional aspects of patient benefit (e.g. patient
      satisfaction) and health-care expenditures (e.g. over-the-counter medications,
      specialist visits, hospitalizations) must be included in an evaluation of the
      value of a particular diagnostic test, treatment, clinical guideline or disease
      management strategy. As a result of the high quality and quantity of data
      emerging, it can be safely said that H. pylori eradication is cost-effective in
      selected patient populations: newly documented peptic ulcer disease; history of
      peptic ulcer disease and taking maintenance therapy; and suspected peptic ulcer
      disease using a serological test to guide initial treatment. The role of
      eradication in other areas, for example, patients with non-ulcer dyspepsia and
      screening to prevent gastric cancer, remains to be seen. In addition to the
      performance of rigorous studies, researchers must respond to the 'information
      overload' on busy clinicians, by effectively disseminating their findings. If
      data generated from outcomes research are not integrated into everyday clinical
      practice, the enormous benefits associated with H. pylori eradication will not be
      achieved.

PMID- 9146796
TI  - Helicobacter pylori eradication and its implications for the future.
AB  - It has become evident that at least some strains of Helicobacter pylori are
      pathogenic for humans. However, H. pylori are highly diverse and at least part of
      this variation involves characteristics related to pathogenicity. A large amount
      of evidence suggests that H. pylori infection of humans is ancient, and in
      general, the interaction is not terribly destructive. However, we should try to
      understand better the risks associated with infection with particular H. pylori
      strains, and limit treatment to those situations in which the indications for
      eradicating H. pylori are clear-cut. It is entirely possible that some H. pylori
      strains are commensals, and that others are symbionts. Eradicating those
      infections could ultimately cause more harm than good. It is too early to reach
      firm conclusions about whether all H. pylori infections need to be eradicated.

PMID- 9146797
TI  - The future of Helicobacter pylori eradication: a personal perspective.
AB  - Future changes in the use of Helicobacter pylori eradication therapy first will
      involve a decision-making process to determine which individuals require testing.
      Clearly, only persons who require therapy need to be diagnosed and, at present,
      the indications for therapy are constantly expanding. The author takes the view
      that everyone with H. pylori would be better off without the bacterium, but
      accepts that in many countries resources are inadequate to achieve this goal.
      Where antibiotic therapy for H. pylori fails due to a resistant organism, second
      treatment must include a different class of antibiotic. When a third therapy is
      contemplated, antibiotic sensitivity studies are usually necessary. In developing
      counties where reinfection with H. pylori is common, lesser goals than permanent
      cure might be appropriate. Thus, selected patients could have H. pylori
      suppressive therapy to prevent full expression of H. pylori-associated disease,
      or to prevent reinfection after an initial eradicative therapy. After considering
      all these alternatives, one must conclude that a vaccination strategy, if safe
      and cost effective, is the ideal future therapy.

PMID- 9146798
TI  - Noncompartmental models of whole-body clearance of tracers: a review.
AB  - Noncompartmental models are defined as models that allow for transport of
      material through regions of the body that are not necessarily well-mixed or of
      uniform concentration. The clearance of a substance of interest (metabolite or
      drug) from a noncompartmental system will not necessarily be governed by a sum of
      exponentials or even be describable by a set of ordinary differential equations.
      The model may involve diffusion or other random walk processes, leading to the
      solution in terms of the partial differential equation of diffusion or in terms
      of probability distributions. It may use the theory of linear systems to obviate
      the need for defining any precise anatomical structure. A number of the models
      reviewed deal with plasma clearance curves that are best described by power
      functions of time. Circulatory models are reviewed from their inception to the
      present. Recent studies on clearance as a fractal process are introduced.

PMID- 9146799
TI  - A dynamic model of the hand with application in functional neuromuscular
      stimulation.
AB  - Potential hand function in people with tetraplegia was evaluated using a three
      dimensional dynamic mathematical model. The model was used to evaluate hand
      positioning, grasp force, and the outcome of surgeries such as tendon transfers
      and joint fusion, in situations typical of those encountered when using
      functional neuromuscular stimulation to restore function in people with
      tetraplegia. In the model, the hand is treated as a jointed multibody system.
      Each joint is subjected to muscle moments, passive joint moment, and moments due
      to grasp forces. Model simulations showed that function was highly dependent on
      both muscle strength and joint passive moments. The potential for tendon
      transfers, such as the Zancolli-lasso and intrinsicplasty, plasty, to improve
      hand function was demonstrated, but their value is subject-dependent. It was also
      shown that activation of multiple thumb muscles (adductor pollicis, abductor
      pollicis brevis, and flexor pollicis longus) without interphalangeal joint fusion
      can provide convenient lateral pinch posture with approximately 70% more grip
      force than a currently used method, which includes joint fusion but requires only
      one muscle. Finally, a grasp protocol was introduced and shown successful in
      palmar grasp and hold of movable cylindrical objects using only extrinsic
      muscles, provided the fingers could be extended sufficiently to enclose the
      object.

PMID- 9146800
TI  - Digital processing of the current noise evoked by kainate in cerebellar granule
      cells.
AB  - Current induced in cultured cerebellar granule cells by the bath application of
      kainate (500 microM) was measured using the conventional patch-clamp technique.
      Two different kinds of responses were observed after the agonist perfusion. Some
      cells exhibited small inward whole-cell currents: 116 +/- 40 pA (7 cells) at a
      clamp potential of -60 mV; in other cells, the agonist induced significantly
      larger currents: 420 +/- 35 pA (6 cells) at a clamp potential of -60 mV. The
      current flowing in the agonist-activated ionic channels was indirectly estimated
      by processing the fluctuations of whole-cell current by means of an original
      parametric method. Mean conductance of the underlying channels was then
      determined from the single-channel current estimated at different clamp
      potentials. In the cells exhibiting small inward currents, the mean conductance
      was equal to 0.5 +/- 0.2 pS (7 cells), whereas in the cells with large inward
      currents it was 3 +/- 0.4 pS (6 cells). This result gives a coherent explanation
      of the different kinds of responses observed at macroscopic level in the whole
      cell current and confirms that kainate-activated channels can exhibit different
      levels of conductance.

PMID- 9146801
TI  - Alteration of hemodynamics in aneurysm models by stenting: influence of stent
      porosity.
AB  - Recent developments in minimally invasive approach to cerebrovascular diseases
      include the placement of stents in arteries for treatment of aneurysms.
      Preliminary clinical observations and experimental studies have shown that
      intravascular stents traversing the orifice may lead to thrombosis and subsequent
      occlusion of the aneurysm. The alterations in vessel local hemodynamics due to
      the introduction of a stent are not yet well understood. We investigated changes
      in local hemodynamics resulting from stent implantation. Pulsatile flow patterns
      in an experimental flow apparatus were visualized using laser-induced
      fluorescence of rhodamine dye. The test cells were constructed in a rectangular
      shape to facilitate an undisturbed longitudinal view of flow patterns in parent
      vessel and aneurysm models with and without porous stents. Woven nitinol stents
      of various porosities (76%, 80%, 82%, and 85%) were investigated. The selected
      fluid dynamic similarity parameters (Reynolds and Womersley numbers) represented
      conditions usually found in high-flow, larger arteries in humans (such as the
      carotid artery) and low-flow, smaller arteries (such as the vertebral artery).
      The mean Reynolds number for the larger arteries was 180, with maximum/minimum
      values of 490/-30 and the Womersley number was 5.3. The mean Reynolds number for
      the smaller arteries was 90, with maximum/minimum values of 230/2, and the
      Womersley number was 2.7. For the larger arteries modeled, placement of a stent
      of the lowest porosity across the aneurysm orifice resulted in reduction of
      aneurysmal vortex speed and decreased interaction with parent vessel flow. For
      smaller arteries, a stent of the same porosity led to a substantial reduction of
      parent vessel/aneurysmal flow interaction and the appearance of a
      nonrecirculating crescent of fluid rich in rhodamine dye in the aneurysm dome.
      Our results can help explain in vivo thrombus formation within an aneurysm after
      placement of a stent that is compatible with local hemodynamics.

PMID- 9146802
TI  - A theoretical unidirectional valve based on functional collapse of blood vessels
      in the penis.
AB  - A model of a vessel exposed to external pressure was developed. Analytical
      derivation resulted in closed-form expressions describing pressure-flow relation
      in the vessel. These expressions describe a behavior of a unidirectional leaky
      valve. The vessel model was used to represent internal arteries and veins in the
      penis. Together with a compliant chamber representing the corpus cavernosum, the
      model demonstrates the valve action of the partially collapsed vessels during
      penile erection. This explains observations regarding arterial backflow during
      erectile contraction of the ischiocavernous muscles and demonstrates the
      differences in development of tumescence and rigidity.

PMID- 9146803
TI  - Effects of rotational myocardial anisotropy in forward potential computations
      with equivalent heart dipoles.
AB  - Rotating fibers in the heart lead to a myocardium of inhomogeneous anisotropic
      conductivity. Besides affecting the activation isochrones, this anisotropy
      modifies the equivalent dipoles used in calculating extracardiac potentials,
      rendering them oblique rather than normal to the activation wavefront due to an
      added axial dipole component oriented along the fibers. Herein, however,
      consequences of the assumption usually made in forward potential calculations
      that the equivalent dipoles act in a myocardium that is homogeneous and isotropic
      are examined. A layered inner block representing the heart was placed inside an
      outer block representing an isotropic volume conductor. Fiber direction in the
      inner block rotated uniformly from layer to layer. Current dipoles of different
      orientations were placed in the inner block and the potentials calculated
      everywhere. Effects of the anisotropy of the inner block were gauged by computing
      an equivalent dipole that best fit the outer block surface potentials. For volume
      conductor conductivities close to that of the torso, the anisotropy diminished
      dipoles oriented along the fibers. Since the intraventricular blood masses in the
      heart also diminish such dipoles, these reductions of the axial component may
      explain the success of heart model simulations that ignore this component.

PMID- 9146804
TI  - Distribution of contact force during impact to the hip.
AB  - Hip fracture is a common, costly, and debilitating injury occurring primarily in
      the elderly. Commonly viewed as a consequence of osteoporosis, it is less often
      appreciated that > 90% of hip fractures are caused by falls, and that fracture
      risk is governed not only by bone fragility, but also by the mechanics of the
      fall. Our goal is to develop experimental and mathematical models that describe
      the dynamics of impact to the hip during a fall, and explain the factors that
      influence hip contact force and fracture risk during a fall. In the current
      study, we used "pelvis release experiments" to test the hypothesis that, during a
      fall on the hip, two pathways exist for energy absorption and force generation at
      contact: a compressive load path directly in line with the hip, and a flexural
      load path due to deformation of muscles and ligaments peripheral to the hip. We
      also explored whether trunk position or muscle contraction influence the body's
      impact response and the magnitude of force applied to the hip during a fall. Our
      results suggest that only 15% of total impact force is distributed to structures
      peripheral to the hip and that peak forces directly applied to the hip are well
      within the fracture range of the elderly femur. We also found that impacting with
      the trunk upright significantly increases peak force applied to the hip, whereas
      muscle contraction has little effect. These results should have application in
      the development of fracture risk indices that incorporate both fall severity and
      bone fragility, and the design of interventions such as hip pads and energy
      absorbing floors that attempt to reduce fracture risk by decreasing in-line
      stiffness and hip contact force during a fall.

PMID- 9146805
TI  - Approximate minimum bias multichannel spectral estimation for heart rate
      variability.
AB  - Spectral decomposition of variations in heart rate permits noninvasive
      measurement of autonomic nervous activity in humans and animals. Autonomic
      metrics based on spectral analysis are useful in monitoring clinical conditions
      such as diabetic neuropathy and reinnervation in heart transplant patients. A
      persistent problem in deriving such autonomic measures is the prerequisite of an
      accurate and unbiased power spectrum of heart rate variability (HRV). Numerous
      parametric and nonparametric power spectrum estimators have been introduced, each
      with its own advantages and drawbacks. Estimator bias has received little
      attention, despite the fact that at least one common HRV spectrum estimator, the
      autoregressive method, is known to exhibit bias even in idealized circumstances.
      We introduce an approximately minimum bias, nonparametric, multichannel spectrum
      estimation procedure for HRV and contemporaneous signals. The procedure, which is
      designed specifically for irregular sampling, does not require data segmentation
      and provides statistically consistent, low variance multichannel spectrum
      estimates. Estimator performance on simulated and clinical data is presented and
      compared with results from autoregressive models and Welch periodograms with and
      without compensation for irregular sampling. Results indicate that the proposed
      method exhibits advantages over conventional HRV spectrum estimators. Relative
      computational complexity of the proposed method is also considered.

PMID- 9146806
TI  - Image enhancement of the in vivo leukocyte-endothelium contact zone using optical
      sectioning microscopy.
AB  - A major determinant of the strength of leukocyte [white blood cell (WBC)] to
      endothelium [endothelial cell (EC)] adhesion is the contact area formed between
      the two cells, which is often obscured by out-of-focus information inherent to
      intravital microscopy. To improve visualization of the WBC-EC contact zone,
      techniques of optical sectioning microscopy were developed to enhance brightfield
      images of WBC-EC adhesion in postcapillary venules of the mesentery of the rat. A
      50x/1.0 NA objective was held in a piezoelectric mount that was computer-driven,
      and video images were obtained by digitizing images from a CCD camera while
      focusing through the vertical direction in 1 micron steps over a depth of 16
      microns. Using measurements of the microscope's optical transfer function,
      deconvolution of the central image was performed in the Fourier domain using the
      technique of singular value decomposition with Tikhonov-Miller regulation to
      remove out-of-focus information. Measurement of the length of the WBC-EC contact
      zone (LC) in the original images yielded values on the order of 4.32 +/- 1.08
      microns (mean +/- SD). The enhanced images showed a significantly 35% smaller LC
      equal to 2.78 +/- 0.70 micron. Topical application of the chemoattractant f-met
      leu-phe resulted in a 26% increase in LC to 3.49 +/- 0.72 micron, thus suggesting
      that upregulation of adhesion molecules on the WBC membrane results in the
      recruitment of additional membrane area from surface ruffles into the zone of
      adhesion. Other advantages of the deconvolution were to visualize structural
      characteristics of the microvascular wall and parenchymal tissue in greater
      detail. Thus, brightfield optical sectioning microscopy may provide a valuable
      tool for in vivo studies of the microvasculature, and serves as a useful
      alternative to fluorescence microscopy without the undesirable effects of
      exogenous fluorophores and exposure to ultraviolet radiation.

PMID- 9146807
TI  - Accuracy of the inverse Womersley method for the calculation of hemodynamic
      variables.
AB  - We have studied the accuracy of the inverse Womersley method, a linear theory for
      the calculation of hemodynamic variables from measured volumetric flow rate or
      centerline velocity, for two canine arteries with different degrees of arterial
      wall motion and taper. The results from the linear theory are compared with the
      estimates from the nonlinear theory of Ling and Atabek for a canine thoracic
      aorta and femoral artery. For the thoracic aorta, the linear theory
      underestimates the mean wall shear stress by as much as 77%, when compared with
      the nonlinear theory. For the femoral artery, on the other hand, the mean wall
      shear stress value is underestimated by as much as 23%. Estimates of other
      hemodynamic variables show similar discrepancies between the nonlinear and linear
      theories. Thus, the inverse Womersley method does not give accurate estimates of
      hemodynamic quantities. This failure results from the neglect of convective
      accelerations due to arterial wall motion and taper, with the neglect of arterial
      taper leading to the largest errors.

PMID- 9146808
TI  - Efficient numerical methods for nonlinear-facilitated transport and exchange in a
      blood-tissue exchange unit.
AB  - The analysis of experimental data obtained by the multiple-indicator method
      requires complex mathematical models for which capillary blood-tissue exchange
      (BTEX) units are the building blocks. This study presents a new, nonlinear, two
      region, axially distributed, single capillary, BTEX model. A facilitated
      transporter model is used to describe mass transfer between plasma and
      intracellular spaces. To provide fast and accurate solutions, numerical
      techniques suited to nonlinear convection-dominated problems are implemented.
      These techniques are the random choice method, an explicit Euler-Lagrange scheme,
      and the MacCormack method with and without flux correction. The accuracy of the
      numerical techniques is demonstrated, and their efficiencies are compared. The
      random choice, Euler-Lagrange and plain MacCormack method are the best numerical
      techniques for BTEX modeling. However, the random choice and Euler-Lagrange
      methods are preferred over the MacCormack method because they allow for the
      derivation of a heuristic criterion that makes the numerical methods stable
      without degrading their efficiency. Numerical solutions are also used to
      illustrate some nonlinear behaviors of the model and to show how the new BTEX
      model can be used to estimate parameters from experimental data.

PMID- 9146809
TI  - Michaelis-Menten kinetics model of oxygen consumption by rat brain slices
      following hypoxia.
AB  - In the present study, we have measured partial pressure of oxygen (pO2) profiles
      through rat brain slices before and after periods of hypoxia (5 and 10 min) to
      determine its effect on tissue oxygen demand. Tissue pO2 profiles were measured
      through rat cerebral cortex slices superfused with phosphate buffer using oxygen
      (O2)-sensitive microelectrodes at different times in controls [40% O2 balance
      nitrogen (N2)], and at different times before and after 5 or 10 min of hypoxia
      (100% N2). A one-dimensional, steady-state model of ordinary diffusion with a
      Michaelis-Menten model of O2 consumption where the maximal O2 consumption (Vmax)
      and the rate at half-maximal O2 consumption (Km) were allowed to vary was used to
      determine the kinetics of O2 consumption. Actual pO2 profiles through tissue were
      fitted to theoretical profiles by a least-squares method. Vmax varied among
      penetrations in a control slice and among slices. Vmax seemed to decrease after
      hypoxic insult, but the change was not statistically significant. The Km value
      measured before hypoxia was lower than the first Km value measured after the end
      of hypoxia, indicating that hypoxia induced a compensatory change in the
      metabolic state of the tissue. Km increased immediately after both 5- and 10-min
      hypoxic insults and returned to normal after recovery for each case. It seems
      that during and immediately after short periods of hypoxia, Km increases from
      near zero but returns to normal values within a few minutes.

PMID- 9146810
TI  - Development of a side-view chamber for studying cell-surface adhesion under flow
      conditions.
AB  - Observing microscopic specimens is often useful in studies of cellular
      interaction with a vascular wall. We have developed an in vitro side-view flow
      chamber that permits observations from the side of the cell's contact with
      various adhesive surfaces under dynamic flow conditions. This side-view flow
      chamber consists of two precision rectangular glass tubes called microslides. A
      smaller microslide is inserted into a larger one to create a flow channel with a
      flat surface on which either cultured vascular endothelium can be grown or
      purified adhesion molecules can be coated. Two optical prisms with a 45 degrees
      chromium-coated surface are used along the flow channel to generate light
      illumination and observation pathways. The side-view images of cell-substrate
      contact can be obtained using a light microscope. This design allows us not only
      to measure the effects of flow on cell-surface adhesion strength, but also to
      have close observation of cell deformation and adhesive contact to various
      surfaces in shear flow. In addition, this chamber can readily serve for a
      conventional top-view flow channel, similar to the parallel-plate flow chambers
      used in many areas. The development of such a side-view flow chamber can be
      beneficial to various in vitro applications in cellular studies that require an
      edge view, especially for various cell interactions with cultured vascular
      endothelium or surfaces containing single-type adhesive molecules under flow
      conditions.

PMID- 9146811
TI  - The pipette aspiration applied to the local stiffness measurement of soft
      tissues.
AB  - A simple method of identifying the initial slope of the stress-strain curve
      (i.e., Young's modulus of the soft tissue) by introducing the pipette aspiration
      technique is presented. The tissue was assumed to be isotropic and
      macroscopically homogeneous. Numerical simulations by the linear finite element
      analysis were performed for the axisymmetric model to survey the effects of
      friction at the tissue-pipette contact boundary, pipette cross-sectional
      geometry, relative size of the specimen to the pipette, and the layered
      inhomogeneity of the specimen tissue. The friction at the contact region had
      little effect on the measurement of Young's modulus. The configuration of the
      pipette was shown to affect the measurement for small pipette wall thickness. The
      measurement also depended on the relative size of the specimen to the pipette for
      relatively small specimens. The extent of the region contributing to the
      measurement was roughly twice the inside radius of the pipette. In this region,
      the maximum stress did not exceed the level of the aspiration pressure, with only
      minor exceptional locations. Calculation of strain energy components indicated
      that the major contributions to the deformation under pipette aspiration were by
      the normal extension and shear deformation in pipette axial direction.
      Experimental verification of the present method for the isotropic, homogeneous
      artificial material is also presented.

PMID- 9146812
TI  - Effect of testosterone administration on sexual behavior and mood in men with
      erectile dysfunction.
AB  - This double-blind placebo controlled, cross-over study was carried out to assess
      the effect of testosterone administration on sexual behavior mood, and
      psychological symptoms in healthy men with erectile dysfunction. Biweekly
      injections of 200 mg of testosterone enanthate were given over a period of 6
      weeks separated by a washout period of 4 weeks. Blood samples for hormonal
      assessment, behavioral and psychological ratings were obtained prior to each
      injection. Luteinizing hormone remained significantly depressed but circulating
      testosterone had returned to baseline levels by 2 weeks following each hormonal
      injection. The ejaculatory frequency during the testosterone phase was
      statistically higher than during the placebo phase. There were marked, although
      statistically nonsignificant, increases in median frequency of reported sexual
      desire, masturbation, sexual experiences with partner, and sleep erections during
      the testosterone period. Testosterone did not have demonstrable effects on
      ratings of penile rigidity and sexual satisfaction. Mood variables and
      psychological symptoms did not change following hormonal administration. Results
      suggest that androgen administration to eugonadal men with erectile dysfunction
      may activate their sexual behavior without enhancing erectile capacity and
      without effects on mood and psychological symptoms.

PMID- 9146813
TI  - The perception of sexual attractiveness: sex differences in variability.
AB  - Results of three independent studies supported predictions derived from
      evolutionary theory: Men's assessments of sexual attractiveness are determined
      more by objectively assessable physical attributes; women's assessments are more
      influenced by perceived ability and willingness to invest (e.g., partners' social
      status, potential interest in them). Consequently, women's assessments of
      potential partners' sexual attractiveness and coital acceptability vary more than
      men's assessments. The proposition that polygamous women's assessments of men's
      sexual attractiveness vary less than those of monogamous women (because the
      former allegedly are more influenced by target persons' physical attributes) was
      also tested. In Study 1 male college students showed more agreement than females
      in their rankings of the sexual attractiveness of opposite-sex target persons.
      Target persons' flesh and bodily display enhanced this sex difference. In Study 2
      men exhibited less variance than did women in their ratings of target persons'
      acceptability for dating and sexual relations. Women who viewed models described
      as having low status showed more variability than did women in the high-status
      condition. In Study 3 women showed more variability than men did in their ratings
      of 20 opposite-sex celebrities' sexual attractiveness. Studies 2 and 3 included
      the Sociosexual Orientation Inventory (SOI)-a measure of polygamous attitudes and
      behavior. Women's SOI scores did not affect the variability of their assessments
      in either Study 2 or 3. In Study 3 men with low SOI scores showed less
      variability than did men with high SOI scores. Alternative explanations of the
      findings are examined. Theoretical and empirical implications are discussed.

PMID- 9146814
TI  - Dimensions of AIDS knowledge and risky sexual practices: a study of northern Thai
      males.
AB  - The relation between AIDS-related knowledge and sexual risk-taking for a sample
      of young men living in northern Thailand was examined. Data were collected during
      the fall of 1991. The sample of 1472 men includes university students, soldiers,
      store clerks, and laborers. Recent commercial sex patronage was variable among
      the subgroups, and consistent condom use among these recent patrons was far from
      universal. Several important misunderstandings among our respondents regarding
      the AIDS virus were identified. These misconceptions were most common among men
      of relatively low socioeconomic status (laborers and soldiers). Factor analysis
      identified four distinct domains of AIDS knowledge among the student and soldier
      groups: knowledge about the mechanics of contagion, knowledge about the
      consequences of infection, knowledge about appropriate strategies for avoiding
      the virus, and knowledge regarding inappropriate strategies for avoiding the
      virus. In multivariate logistic regression, knowledge about inappropriate
      strategies and knowledge about contagion were the only two domains predictive of
      recent commercial sex patronage: Men with a relatively good understanding
      regarding the inefficacy of inappropriate strategies and the mechanics of
      contagion had lower odds of recent commercial sex patronage compared with men who
      had a relatively poor understanding of these domains of AIDS knowledge. In the
      condom use analysis, knowledge about both appropriate and inappropriate
      strategies was predictive of consistent condom use among recent commercial sex
      patrons. Thus programs should attempt to improve knowledge about strategies for
      avoiding the virus and the mechanics of contagion. Special efforts should be made
      to debunk existing myths about the perceived effectiveness of inappropriate
      strategies.

PMID- 9146815
TI  - Sexual content-induced delay with double-entendre words.
AB  - Seventy-three men and 72 women made lexical decisions to target words that
      followed sentences constructed so that the last word was a sexual double
      entendre. Prime target relatedness, erotic versus nonerotic target, stimulus
      onset asynchrony, and participant's gender were varied in a between-subjects
      design. A second analysis that substituted sentence context for prime target
      relationship also was conducted. Data were collected on the emotionality and
      social acceptability of priming sentences and target words. Results revealed
      that, as with previous research on neutral words, prime target relatedness
      facilitated lexical decisions. Additionally, there was evidence of slowing in
      making lexical decisions when erotic material was presented or was part of a
      contextual bias. This delay was accentuated in women. A model that proposes that
      sexual words evoke a more complex processing sequence is presented. The model
      suggests that appraisal and checking or editing mechanisms, which are accentuated
      in women, help explain the phenomenon.

PMID- 9146816
TI  - The prevalence and nature of biphobia in heterosexual undergraduate students.
AB  - Little scientific attention has been paid to bisexuality or to societal attitudes
      about bisexual people. Often, biphobia has been assumed to be identical to
      homophobia. In this study, 229 heterosexual undergraduate students rated their
      degree of agreement to stereotypical statements about bisexuality and provided
      information on their attitudes about the acceptability of bisexual, gay, and
      lesbian people. Although there was a high degree of correlation between biphobia
      and homophobia, negative attitudes about bisexuals, men in particular, were more
      prevalent than negative attitudes about lesbians or gay men. Biphobia and
      homophobia should be considered related, but distinct, phenomena.

PMID- 9146818
TI  - The meta-chlorophenylpiperazine challenge test in cocaine addicts: hormonal and
      psychological responses.
AB  - We report on the neuroendocrine and psychological responsivity of 31 cocaine
      addicts and 14 controls to the serotonergic agonist, meta-chlorophenylpiperazine
      (m-CPP) (0.5 mg/kg p.o.). Cocaine addicts were subdivided into subjects with
      aggressive tendencies and other features similar to those found in type 2
      alcoholics and subjects without these features. Following m-CPP, aggressive and
      nonaggressive patients had a significantly blunted prolactin response compared to
      controls, but there was no difference between the two patient subgroups. There
      was no difference between the cortisol responses of nonaggressive patients and
      controls, but aggressive patients had a significantly blunted cortisol response
      compared to controls and nonaggressive patients. Both patient subgroups reported
      more intense "activation-euphoria" and "high" responses following m-CPP than
      controls. These results could indicate the existence of alterations along
      serotonergic pathways in cocaine addicts taken as a group. In addition, a
      subgroup of patients who could be described as type 2 cocaine addicts appear to
      be biologically different from healthy subjects and from other cocaine addicts as
      indicated by a greater cortisol blunting following m-CPP.

PMID- 9146817
TI  - Impaired vascular smooth muscle nitric oxide-dependent relaxation in human
      coronary arteries from "transplanted heart vasculopathy".
AB  - The long-term prognosis after heart transplant is mainly determined by the
      development of transplant vasculopathy. The pathogenic mechanism of transplant
      vasculopathy remain uncertain, although endothelial dysfunction has been
      postulated. The objective of this work is to evaluate the smooth muscle and
      endothelium nitric oxide relaxing mechanisms in coronary arteries from patients
      with transplant vasculopathy. We studied human coronary arteries obtained from
      heart transplant surgery specimens of patients with heart transplant
      vasculopathy, ischaemic cardiopathy or dilated cardiomyopathy. Rings from the
      coronary arteries were mounted on stainless steel hooks in 40 ml organ bath. The
      tissues were contracted with phenylephrine (approx. ED 80-90) and concentration
      response curves were performed with glyceryltrinitrate and acetylcholine.
      Glyceryltrinitrate relaxed arterial rings from patients with dilated
      cardiomyopathy and ischaemic cardiopathy. Arterial rings from patients with heart
      transplant vasculopathy showed a lower response to glyceryltrinitrate.
      Acetylcholine induced dilatation of coronary arteries from dilated cardiomyopathy
      but increased the tension in coronary rings from heart transplant vasculopathy
      and inschaemic cardiopathy. In conclusion, there is a lower response to
      glyceryltrinitrate and a paradoxical response to acetylcholine in arteries from
      patients with transplant vasculopathy. The response to glyceryltrinitrate may be
      a meaningful tool in the early diagnosis of transplant vasculopathy.

PMID- 9146819
TI  - Neurophysiological signs of cocaine dependence: increased electroencephalogram
      beta during withdrawal.
AB  - To determine whether a central nervous system marker of cocaine dependence might
      exist, the resting electroencephalogram (EEG) of 33 drug-free, cocaine-dependent
      men (DSM-III-R criteria) was compared with two control groups [nondrug group (n =
      10) and drug group who abused drugs, but were not cocaine dependent (n = 20)].
      The EEG was recorded from eight sites after about 10 days of monitored abstinence
      (range 4-15 days) on a closed research ward for the drug-using individuals. The
      EEG was recorded for the nondrug control group as outpatients. The drug history
      was determined by the drug history questionnaire and a medical screening
      interview. The percent of EEG beta activity for the cocaine-dependent subjects
      was greater than that of both control groups (p < .05) as well as a normative
      database (HZI: Tarrytown, NY). The percent of EEG beta in frontal and central
      areas of the cocaine-dependent individuals was correlated with the frequency of
      cocaine use during the last 30 days. High levels of EEG beta may be a
      neurophysiological withdrawal sign in cocaine-dependent men.

PMID- 9146821
TI  - Cavum septi pellucidi in normals and patients with schizophrenia as detected by
      magnetic resonance imaging.
AB  - Cavum septi pellucidi (CSP) is a cavity between the two leaflets of the septum
      pellucidum. CSP is a developmental anomaly, yet the pathologic implications, if
      any, of an abnormally large CSP remain unclear. The reported incidence of CSP
      among normal populations varies greatly from 0.15% to 85%. Several studies have
      suggested that there is a higher incidence of CSP in patients with schizophrenia.
      We conducted a thin-slice magnetic resonance imaging study to evaluate the
      prevalence of CSP in a sample of 75 controls and 55 patients. There was a high
      incidence of small CSP among both groups: 58.8% in the controls and 58.2% in the
      patients, suggesting that a small cavum could be considered a normal variant;
      however, the patient group had significantly higher incidence of large CSP
      (20.7%) compared to the normal group (3%). The patients with large CSP were all
      male.

PMID- 9146820
TI  - Buprenorphine and naloxone interactions in methadone maintenance patients.
AB  - Buprenorphine is undergoing clinical trials for the treatment of opiate
      addiction. Although the abuse liability of sublingual buprenorphine is low,
      reports of intravenous abuse have appeared. This study describes the physiologic
      and subjective effects of intravenously administered buprenorphine and naloxone
      given alone and in combination to methadone-maintained patients (40-60 mg/day).
      On four separate occasions at least 1 day apart, 6 subjects were administered
      either 0.2 mg buprenorphine, 0.1 mg naloxone, 0.2 mg buprenorphine and 0.1 mg
      naloxone in combination, or placebo. One male subject quit the experiment after
      three sessions because of excessive opiate withdrawal. Buprenorphine produced no
      significant physiologic or subjective effects. Naloxone produced marked opiate
      withdrawal symptoms. Buprenorphine in combination with naloxone produced
      characteristic physiologic and subjective opiate antagonist-like symptoms and
      signs. The parenteral abuse potential of the buprenorphine and naloxone
      combination is discussed.

PMID- 9146823
TI  - Molecular forms of somatostatin-like immunoreactivity in the cerebrospinal fluid
      of patients with senile dementia of the Alzheimer type.
AB  - In the cerebrospinal fluid (CSF) of 53 patients with senile dementia of the
      Alzheimer type (SDAT) and 12 elderly controls, we measured somatostatin (SLI) and
      its molecular forms: high-molecular weight form (HMV-SST), somatostatin-14 (SST
      14), somatostatin-25/28 (SST-28/25), and des-ala-somatostatin (des-ala-SST) using
      high pressure liquid chromatography (HPLC) and a radioimmunoassay. In SDAT, SLI
      was significantly decreased (p < 0.05) and correlated with dementia scores (r = 
      0.65, p < 0.05). HPLC separation showed a marked heterogeneity of SLI in the CSF
      with a preponderance of SST-14 and SST-25/28. The significant loss of SST-14 (p <
      0.05) in SDAT was found to be correlated with dementia scores (r = 0.65).
      Moreover, qualitative and quantitative changes in the molecular pattern of SLI in
      SDAT indicated dysregulated synthesis and/or processing of somatostatin relating
      to the severity of dementia. The long-term administration of neuroleptics in
      severe cases of SDAT caused a significant increase of SLI (p < 0.05) and
      influenced the ratio of HMV-SST/SST-14 and SST25/28/SST-14.

PMID- 9146822
TI  - Circadian temperature and cortisol rhythms during a constant routine are phase
      delayed in hypersomnic winter depression.
AB  - Circadian temperature, cortisol, and thyroid-stimulating hormone (TSH) rhythms
      during a constant routine were assessed in 6 female controls and 6 female
      patients with hypersomnic winter depression (seasonal affective disorder, SAD)
      before and after morning bright light treatment. After sleep was standardized for
      6 days, the subjects were sleep-deprived and at bed rest for 27 hours while
      rectal temperature, cortisol, and TSH levels were assessed. The minimum of the
      fitted rectal temperature rhythm was phase-delayed in the SAD group compared to
      the controls 5:42 AM vs. 3:16 AM (p < .005); with bright light treatment, the
      minimum advanced from 5:42 AM to 3:36 AM (p = .06). The minimum of the cortisol
      rhythm was phase-delayed in the SAD group compared to the control group, 12:11 AM
      vs. 10:03 PM (P < .05); with bright light treatment, the minimum advanced from
      12:11 AM to 10:38 PM (P = .06) [corrected]. The acrophase of the TSH rhythm was
      not significantly phase-delayed in SAD subjects compared to control, though the
      trend appeared to be toward a phase-delay (p = .07). After bright light therapy,
      the TSH acrophase was not significantly different in the SAD subjects; the trend
      was a phase-advance (p = .09). Overall, the data suggest that circadian rhythms
      are phase-delayed relative to sleep in SAD patients and that morning bright light
      phase-advances those rhythms.

PMID- 9146824
TI  - Plasma sialyltransferase levels in psychiatric disorders as a possible indicator
      of HPA axis function.
AB  - A dysfunction in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis,
      possibly attributed to a change in glucocorticoid receptor (GR) functionality,
      has been implicated in depression. We have measured both lymphocyte GR receptor
      binding parameters and plasma sialyltransferase activity, as a biochemical marker
      of GR function, in two groups of patients suffering from depression or
      schizophrenia and in a group of age- and sex-matched controls. While there was a
      significant increase in plasma cortisol levels in the depressed group, there were
      no changes in the lymphocyte GR binding parameters (K(m) and Bmax). There was,
      however, a significant decrease in the plasma sialyltransferase: cortisol ratio
      in the depressed group suggesting an inability of the raised cortisol levels to
      induce enzyme expression and this ratio may provide a useful biochemical marker
      of cortisol receptor function. Although there was an increase in the plasma
      activity of the alpha 2,6 sialyltransferase isozyme in the schizophrenic group,
      no other changes were determined. Therefore, while the total plasma
      sialyltransferase:cortisol ratio reflects HPA axis function, alterations in
      specific isozyme activity may also be associated with other CNS disease states.

PMID- 9146825
TI  - Depressive disorder due to mitochondrial transfer RNALeu(UUR) mutation.

PMID- 9146826
TI  - Increased intra-abdominal fat deposition in patients with major depressive
      illness as measured by computed tomography.

PMID- 9146827
TI  - Antenatal depression and thyroid antibodies.

PMID- 9146828
TI  - Manipulation of serotonergic status related to subjective and behavioral measures
      of aggression.

PMID- 9146829
TI  - Basal ganglia: beyond sensorimotor control.

PMID- 9146830
TI  - A general method for tree-comparison based on subtree similarity and its use in a
      taxonomic database.
AB  - A number of metrics for comparing the branching structure of trees have been used
      as important tools in the quantitative analysis of evolutionary trees. Less
      attention has been paid to developing a general comparison methodology for
      different leaf-labeled N-trees such as classification trees and various types of
      dendrograms. In this paper a method for measuring overall similarity based on
      subtree similarity is proposed. Association coefficients can be used to measure
      the similarity between each pair of subtrees in two trees, and an algorithm
      called the 'webbing matrix method' is outlined in order to calculate the overall
      similarity in this method. In addition, the use of this method for tree searching
      and tree comparison in a taxonomic database is introduced.

PMID- 9146831
TI  - Dynamical behavior of a neural network with periodical external inputs.
AB  - Localized neural populations in different brain areas can undergo periodical
      external influence. To study this situation we consider the well known model by
      Wilson and Cowan (1972). It describes the evolution of two interconnected
      neuronal subpopulations of excitatory and inhibitory neurons correspondingly.
      Besides, it could be considered as a model of an abstract self-regulatory system.
      We describe and reveal underlying mechanisms of two regimes of forced
      oscillations in the model. In the first one the system acts as a phase
      comparator, demonstrating high sensitivity to a value of a phase shift between
      inputs to excitatory and inhibitory neurons. In the second regime it acts similar
      to a low pass filter: amplitudes of forced oscillations of the both components
      are not small and almost constant for low frequencies of the external input to
      the excitatory subpopulation. But they decrease significantly when the frequency
      becomes rather high. For simplified versions of the model analytical estimates
      for corresponding ranges of parameters are derived. It is shown that they are in
      good agreement with the results of computer simulations.

PMID- 9146832
TI  - Simulation of the clonal growth of Bostrychia radicans (Ceramiales-Rhodophyta)
      using Lindenmayer systems.
AB  - A mathematical model for the clonal growth of the alga Bostrychia radicans was
      constructed based on architectural growth rules and Lindenmayer systems. The
      sequence of theoretical growth and invasive strategy of space is shown in several
      graphical schemes which represent different steps of the model. We postulate that
      Bostrychia radicans has a 'phalanx' strategy of colonization (Lovett Doust, L.
      1981. J. Ecol. 69, 743-755.) based on the biological interpretation of the model
      and field observations.

PMID- 9146833
TI  - The evolution of parallel cellular machines: toward evolware.
AB  - The historical idea of evolving machines has recently resurfaced as the nascent
      field of bio-inspired systems and evolvable hardware. This paper describes the
      cellular programming approach used to evolve parallel cellular machines,
      presenting its application to six computational problems: density,
      synchronization, ordering, boundary computation, thinning and random number
      generation. Our results show that successful machines can be evolved to solve
      these tasks. The methodology described herein represents one possible approach to
      attaining truly evolving ware, evolware, with current implementations centering
      on hardware, while raising the possibility of using other forms in the future,
      such as bioware. The paper presents work in progress, the aim being to give an
      account of results obtained to date, ending with a list of several open issues
      for future research.

PMID- 9146834
TI  - A logic-based dynamical theory for a genesis of biological threshold.
AB  - To help the study of constructing a formal neuron by computer, we propose a logic
      based dynamical theory for a genesis of the biological threshold which specific
      proteins, such as ion channel proteins, or their networks can produce. By viewing
      such a protein or a protein network as a computational machine, the statements
      concerning the states of reaction chains which eventually activate or inactivate
      the protein are treated. By introducing dynamical systems, associated with an
      inference process based on statements with continuous truth values, we
      investigated invariant characters of such dynamics and we obtained a sigmoidal
      function for an invariant distribution function of the truth values. The domain
      of solutions of the functional equations regarded as representing the self
      description of proteins or protein networks as a machine indicates the emergence
      of a threshold, namely the realization of dyadic value, 0 or 1, based on the
      continuous truth values. The results obtained may highlight the mechanism of
      neuronal threshold in a framework which differs from population dynamics. The
      derived dynamical systems may also provide a simple model of 'demon' rectifying
      the thermal fluctuations to drive unidirectional movements.

PMID- 9146835
TI  - Evanescent (tunneling) photon and cellular "vision'.
AB  - The existence of a rudimentary form of cellular 'vision' was discovered
      experimentally by Albrecht-Buehler. He found that Swiss 3T3 cells approached
      distant infrared light spots and suggested that the most likely explanation for
      this phenomenon involves the long-range processing of electromagnetic signals by
      the cells. In this paper, a theoretical possibility of this phenomenon is
      presented within the fully quantum theoretical framework of the electromagnetic
      field and water. By taking into account the usually neglected interaction between
      the electric dipole field of water molecules and the quantized electromagnetic
      field, the dynamically ordered region of water surrounding the cell up to the
      coherence length < 50 microns is shown to play the role of a nonlinear coherent
      optical device through which the cells receive electromagnetic signals from
      distant light spots. The electromagnetic signals for the cell Albrecht-Buehler
      found are shown to consist of evanescent photons (i.e. soft polaritons) tunneling
      through the dynamically ordered region of water between the cell and the distant
      light spot. In contrast to the (normal) vision of animals realized by receiving
      (normal) photons, cellular "vision' is found to be realized by receiving
      evanescent photons. It is also suggested that the existence of the dynamically
      ordered region of water realizing a boson condensation of evanescent photons
      inside and outside the cell can be regarded as the definition of life.

PMID- 9146836
TI  - Recovery and rehabilitation following traumatic brain injury.
AB  - Although most patients are discharged following traumatic brain injury (TBI) with
      "good recovery', recent reports indicate that many have persistent
      neuropsychological deficits. The purposes of this study were to: (1) determine if
      functional, neuropsychological and social outcome at 3 and 6 months in patients
      hospitalized following TBI could be ascertained via telephone follow-up, and (2)
      assess use of rehabilitation services in this population. Patients were
      identified through acute hospital admissions. A trained nurse practitioner
      abstracted data from acute charts. Using the Functional Independence Measure
      (FIM), Neurobehavioral Rating Scale (NRS), Telephone Interview for Cognitive
      Status (TICS), and a social questionnaire she obtained follow-up information at 3
      and 6 months post-injury. Of 74 patients initially identified, 51 and 48 were
      available at 3 and 6 months, respectively. Most experienced mild to moderate TBI.
      Physical disability was minimal at follow-up as indicated by the FIM.
      Approximately half of the patients were rated cognitively impaired on the TICS at
      3 months and over one-third remained impaired at 6 months. At 6 months 60.5%
      remained unemployed. Only eight of the 67 discharged survivors received any
      rehabilitation services. A brief telephone follow-up appears to be a cost
      effective way to ascertain functional and neuropsychological outcome in TBI
      survivors. Since few of these patients received rehabilitation, a telephone
      follow-up may identify those who would potentially benefit from additional
      rehabilitation services.

PMID- 9146837
TI  - Conversation with traumatically brain-injured individuals: a controlled study of
      behavioural changes and their impact.
AB  - The conversations of 62 traumatically brain-injured (TBI) patients, assessed
      between 6 months and 3 years post-injury, were compared with those of an
      orthopaedic control (OC) group (n = 25). Conversations involving TBI subjects
      were rated as significantly less interesting, less appropriate, less rewarding
      and more effortful than interactions involving OC subjects, and were
      characterized by differences in the frequency of prompt usage and turn duration.
      Furthermore, measures of turn duration and prompt frequency were significantly
      associated with the perceived quality of conversation. These findings provide a
      microbehavioural description of the social process through which TBI individuals
      fail to adequately reinforce others.

PMID- 9146838
TI  - Incidence and sequelae of symptomatic venous thromboembolic disease among
      patients with traumatic brain injury.
AB  - Venous thromboembolism (VTE) is a potentially life-threatening complication among
      patients with traumatic brain injury (TBI). However, few reports describe the
      incidence of this important disease. We reviewed the incidence of symptomatic VTE
      among 124 consecutive admissions with TBI to a free-standing rehabilitation
      hospital over an 18-month period. Four patients manifested evidence of VTE within
      2 months of injury: two with leg swelling, one with an oedematous arm, and one
      with respiratory distress. None of the patients with suspected VTE received
      prophylactic anticoagulant therapy. Diagnosis of VTE was confirmed with venograph
      in two of the four patients. Although VTE is frequently asymptomatic, the
      incidence of symptomatic VTE (1.6%) among this series of rehabilitation
      inpatients with TBI still appears surprisingly low. These results have
      implications regarding the utility of non-invasive diagnostic screening of
      asymptomatic VTE and routine anticoagulant prophylaxis of high-risk patients with
      TBI.

PMID- 9146839
TI  - Cognitive effects of antipsychotic agents in persons with traumatic brain injury.
AB  - Over 1 million survivors of traumatic brain injury receive maintenance
      pharmacotherapy, of which a substantial number receive antipsychotic agents for
      the treatment of psychoses, agitation and aggression, and other maladaptive
      behaviours. In spite of the common clinical uses of antipsychotics, the cognitive
      risks versus benefits are unclear. The purpose of this study was to assess
      differences in cognitive functioning before, during, and after discontinuation of
      antipsychotic agents in inpatients undergoing rehabilitation for traumatic brain
      injury. Neuropsychiatric tests (Reys Auditory-Verbal Learning, Trail Making A&B,
      Digit Span Forwards and Backward) evaluating cognitive skills of verbal ability,
      visuomotor speed, memory, learning, attention, and spatial ability were
      administered to each subject at baseline (immediately prior to tapering or
      discontinuing antipsychotic), when taper reached 50% of baseline dose, 1 week
      after antipsychotic discontinuation, and 3 weeks after discontinuation. These
      data suggest that select areas of cognition improve after antipsychotic
      discontinuation in subjects with traumatic brain injury. The magnitude of
      improvement appeared to be greater after discontinuation with thioridazine, a low
      potency agent, compared to haloperidol, a high-potency agent. Results, although
      very preliminary, support the hypothesis of cholinergic involvement in regulating
      cognitive processes, and this underscores the need for more systematic research
      in this area.

PMID- 9146840
TI  - The malingering of multiple sclerosis and mild traumatic brain injury.
AB  - In this investigation, neuropsychological testing was conducted with 69 college
      students that were instructed to malinger either multiple sclerosis (MS) or
      traumatic brain injury (TIB) or were non-malingering controls. The two
      malingering groups were divided into informed and non-informed groups. The
      informed groups received information concerning their respective condition, and
      the non-informed groups were asked simply to malinger. Generally, all malingering
      groups performed considerably below the levels of non-malingering controls on
      measures of attention, learning and memory, word fluency, abstract reasoning,
      visuoconstruction and manual dexterity. There appeared to be no difference in the
      manner in which subjects attempted to malinger MS as opposed to TBI. However, the
      severity of the portrayed deficit suggested by the test scores was
      disproportionate to the severity of the injury being requested. The pattern of
      deficit presented was quite global, with well below average performance
      demonstrated by all malingering groups across all domains.

PMID- 9146841
TI  - Self-management in the treatment of ataxia: a case study in reducing ataxic
      tremor through relaxation and biofeedback.
AB  - This study examined the effects of relaxation training and biofeedback on the
      ataxic tremor of an adult with an acquired brain injury. The participant was
      taught relaxation techniques before biofeedback was introduced. Once he was
      proficient in relaxation, these skills we used as a foundation for biofeedback
      training. Specific skills crucial to the performance of activities of daily
      living were trained once the participant was able to control the appropriate
      musculature according to an individualized criterion level. These skills included
      eating and the transfer of liquids in a glass. The results demonstrated that the
      participant learned to decrease the amount of tremor that he experienced. As a
      result he was better able to feed himself and to drink from a glass with less
      staff assistance than he had previously required.

PMID- 9146842
TI  - Light and electron microscope study of nerve cells in traumatic oedematous human
      cerebral cortex.
AB  - The cerebral cortex of eight patients with complicated head and brain traumatic
      injuries has been examined with light and transmission electron microscopes. The
      neuronal and neuroglial cell bodies and their processes have been examined to
      study the changes induced by the brain injury and the associated vasogenic and
      cytotoxic, moderate or severe, brain oedema. Light microscopy study showed
      oedematous and ischaemic neurons and neuroglial cells in both moderate and severe
      oedema, and breakdown of the blood-brain barrier with perivascular and
      parenchymatous haemorrhagic foci. Astrocytes and oligodendrocytes exhibited
      oedematous and reactive changes. At the electron microscope level oedematous
      changes were found in intraneuronal and glial somatic compartment. Myelinated
      axons showed clear and dark degenerative features. Beaded dendrites and clear and
      dense synaptic degeneration were also found. The extracellular space appeared
      distended, with the presence of clear and electron-dense haematogenous oedema
      fluid and fibrinous organization. Phagocytosis of degenerated myelinated axons
      and synaptic endings by neuroglial cells and non-nervous invading cells were
      observed. The clinical evolution time of traumatic brain injuries was considered
      in relation to nerve cell degenerative features.

PMID- 9146843
TI  - Subject review on head injury and sexual dysfunction.

PMID- 9146844
TI  - Pharmacoeconomics: basic concepts and terminology.

PMID- 9146845
TI  - The need for large-scale randomized evidence.
AB  - The reliable detection of moderate differences in major health outcomes that
      arise as a result of treatment requires large-scale randomized evidence (and the
      appropriate interpretation of this evidence once it has been generated). This may
      take the form of a single mega-trial or, exceptionally, a meta-analysis of many
      smaller randomized trials may provide worthwhile information. Small or non
      randomized studies cannot generally be trusted to distinguish reliably between a
      moderate benefit, a moderate hazard, and a negligible difference in major
      outcomes. Simple design, streamlined data collection, and use of the "uncertainty
      principle' to guide eligibility would all encourage the recruitment of larger
      samples in randomized trials. Future trials need to adopt these methods in order
      to detect any moderate improvements in major outcomes that may await discovery.

PMID- 9146846
TI  - Pharmacokinetics of thiopentone enantiomers following intravenous injection or
      prolonged infusion of rac-thiopentone.
AB  - AIMS: Thiopentone is administered as a racemate (rac-thiopentone) for induction
      of anaesthesia as well as for neurological and neurosurgical emergencies. The
      pharmacokinetics and pharmacodynamics of rac-thiopentone have been extensively
      studied but the component R-(+)- and S-(-)- enantiomers, until very recently,
      have been largely ignored. METHODS: The present study analyses the
      pharmacokinetics of R-(+)- and S-(-)-thiopentone in 12 patients given rac
      thiopentone intravenously for induction of anaesthesia and five patients given a
      prolonged infusion of rac-thiopentone used for treatment of intracranial
      hypertension. RESULTS: The mean total body clearance (CLT) and apparent volume of
      distribution at steady-state (Vss) showed trends towards higher values for R-(+)-
      than for S-(-)-thiopentone in both patient groups; CLT and Vss of unbound
      fractions of R-(+)- and S-(-)-thiopentone, however, did not show these trends.
      The time courses of R-(+)- and S-(-)- thiopentone serum concentrations were so
      similar that EEG effect could not be attributed to one or other enantiomer. Serum
      protein binding for S-(-)-thiopentone was greater than for R-(+)-thiopentone (P =
      0.02) and 24 h urinary excretion of R-(+)-thiopentone was greater than for S-(-)
      thiopentone (P = 0.03). In one patient, concomitant measurement of CSF and serum
      thiopentone concentrations found that serum: CSF equilibration of unbound
      fractions of both enantiomers was essentially complete. CONCLUSIONS: The study
      was unable to determine any pharmacokinetic difference of clinical significance
      between the R-(+)- and S-(-)-thiopentone enantiomers and concludes that minor
      differences in CLT and Vss could be explained by enantioselective difference
      found in serum protein binding.

PMID- 9146847
TI  - Single dose pharmacokinetics of oral artemether in healthy Malaysian volunteers.
AB  - AIMS: To determine the pharmacokinetics of artemether (ARM) and its principal
      active metabolite, dihydroartemisinin (DHA) in healthy volunteers. METHODS: Six
      healthy male Malaysian subjects were given a single oral dose of 200 mg
      artemether. Blood samples were collected to 72 h. Plasma concentrations of the
      two compounds were measured simultaneously by reversed-phase h.p.l.c. with
      electro-chemical detection in the reductive mode. RESULTS: Mean (+/- s.d.)
      maximum concentrations of ARM, 310 +/- 153 micrograms l-1, were reached 1.88 +/-
      0.21 h after drug intake. The mean elimination half-life was 2.00 +/- 0.59 h, and
      the mean AUC 671 +/- 271 micrograms l-1 h. The mean Cmax of DHA, 273 +/- 64
      micrograms l-1 was observed at 1.92 +/- 0.13 h. The mean AUC of DHA was 753 +/-
      233 micrograms h l-1'. ARM and DHA were stable at < or = -20 degrees C for at
      least 4 months in plasma samples. CONCLUSIONS: The relatively short half-life of
      ARM may be one of the factors responsible for the poor radical cure rate of
      falciparum malaria with regimens employing daily dosing. In view of the rapid
      loss of DHA in plasma samples held at room temperature (26 degrees C) it is
      recommended to store them at a temperature of < or = -20 degrees C as early as
      possible after sample collection.

PMID- 9146848
TI  - Enhanced effect of triazolam with diltiazem.
AB  - AIMS: Triazolam, a triazolobenzodiazepine hypnotic agent, is metabolized by
      CYP3A4. Diltiazem is an inhibitor of this isozyme. The aim of this study was to
      determine if diltiazem affects plasma concentrations of triazolam in humans.
      METHODS: We investigated the interaction between triazolam and diltiazem in a
      randomized, three-phase crossover study. Seven healthy male volunteers received
      orally either a single 0.25 mg dose of triazolam, a 0.25 mg dose of triazolam
      after a 3-day treatment of diltiazem (180 mg day-1), or a placebo. Plasma samples
      were collected to determine triazolam concentration over a 24 h period. The
      pharmacodynamic effects of triazolam were investigated using the peak saccadic
      velocity of eye movements (PSV), electroencephalogram (EEG), and visual analogue
      scale (VAS) through 8 h. RESULTS: Diltiazem pretreatment significantly increased
      the area under the triazolam concentration-time curve (8.0 +/- 2.4 to 18.2 +/-
      3.1 ng ml-1 h; P < 0.001; mean +/- s.d.). Peak triazolam concentration was
      increased (2.1 +/- 0.7 to 3.6 +/- 1.0 ng ml-1, P < 0.05) and the elimination half
      life prolonged (4.1 +/- 2.1 to 7.6 +/- 1.9 h; P < 0.01). The PSV, EEG, and VAS of
      the triazolam plus diltiazem group revealed significant differences from the
      triazolam alone group or the control placebo group. CONCLUSIONS: Diltiazem
      markedly affects the pharmacokinetics of triazolam and increases the intensity of
      its sedative effects. Inhibition of CYP3A isozyme by diltiazem may explain the
      observed pharmacokinetic interaction. Therefore, triazolam should be avoided when
      patients are using diltiazem.

PMID- 9146849
TI  - Concentration-effect relations of glibenclamide and its active metabolites in
      man: modelling of pharmacokinetics and pharmacodynamics.
AB  - AIMS: The main purpose of this paper is to describe the relationship between
      serum concentrations of glibenclamide and its main metabolites and the effects on
      blood glucose levels, the clinically most relevant parameter to assess in
      diabetes. METHODS: Serum concentrations and blood glucose lowering effects
      (expressed as percent blood glucose reduction vs placebo) of glibenclamide (Gb)
      and its active metabolites, 4-trans-hydroxy-(M1) and 3-cis-hydroxy-glibenclamide
      (M2), were analysed in eight healthy subjects participating in a placebo
      controlled, randomized, single-blind crossover study, using intravenous
      administration of each compound as well as oral administration of Gb. RESULTS:
      Plots of % blood glucose reduction vs log serum concentration demonstrated
      counter-clockwise hysteresis for parent drug and its metabolites. An effect
      compartment was linked to appropriate pharmacokinetic models and pharmacokinetic
      and pharmacodynamic modelling was used to fit the pharmacokinetics of Gb by both
      routes and the metabolites for each individual. Based on the individual
      concentration-time profiles a PK/PD-model was applied to all effect data
      simultaneously. An increase in the steady-state serum concentration when the
      effect is 50% of maximal, CEss50, was found in the sequence M1 (23 ng ml-1), M2
      (37 ng ml-1) and Gb (108 ng ml-1). Corresponding interindividual variabilities
      expressed as CV% were 25%, 47% and 26%. The elimination rate constants from the
      effect site (kEO) were estimated and increased in the order M1 (0.178 h-1, CV
      13%), M2 (0.479 h-1, CV 8.5%) and Gb (1.59 h-1, CV 36%). Corresponding
      equilibration half-lives for the effect site (kEO-HL) were 3.9 h, 1.4 h and 0.44
      h. Estimated Emax-values obtained for M1, M2 and Gb were 40% (CV 30%), 27% (CV
      56%) and 56% (CV 14%), respectively. CONCLUSIONS: It is concluded that the two
      major metabolites of Gb are hypoglycaemic in man, that they may have higher
      activity at low concentrations and that they may have a longer effect duration
      than the parent drug.

PMID- 9146850
TI  - Suppression of human monocyte tumour necrosis factor-alpha release by
      glucocorticoid therapy: relationship to systemic monocytopaenia and cortisol
      suppression.
AB  - AIMS: Glucocorticoids suppress the release of tumour necrosis factor-alpha (TNF
      alpha) by macrophages in vitro and cause monocytopaenia in vivo. These actions
      may contribute to anti-inflammatory and immunosuppressant effects. We therefore
      examined relationships between prednisolone concentration, suppression of
      monocyte TNF-alpha release, monocytopaenia and suppression of total cortisol
      concentration in healthy volunteers treated with a single dose (1.5 mg kg-1) of
      the glucocorticoid, prednisolone. METHODS: Monocyte numbers, total cortisol
      concentration and prednisolone concentration were measured in blood samples
      collected over 48 h after the dose. Plasma from these samples was also tested for
      its capacity to suppress lipopolysaccharide-induced TNF-alpha release from
      monocytes in autologous whole blood cultures. RESULTS: At 4 h after the dose,
      monocyte numbers in peripheral blood had fallen to a mean of 18% of the pre-dose
      level whilst plasma total cortisol had fallen to 9% of the pre-dose
      concentration. Monocyte numbers recovered in concordance with elimination of
      prednisolone and there was a significant relative monocytosis at 24 h. The
      recovery of plasma cortisol was delayed in comparison, with cortisol remaining
      significantly suppressed at 24 h. Plasma samples taken at 2 h after the dose
      (corresponding to peak plasma prednisolone concentration) suppressed the
      lipopolysaccharide-stimulated production of TNF-alpha by autologous blood
      monocytes to 27% of pre-dose control. Plasma collected at intervals over the 48 h
      from dosing also suppressed monocyte TNF-alpha release in relation to the
      prednisolone concentration therein. Suppression was largely reversed by the
      glucocorticoid antagonist, mifepristone. A similar relationship between
      prednisolone concentration and TNF-alpha suppression was observed when
      prednisolone was added to blood samples collected from the volunteers when they
      were drug-free. CONCLUSIONS: Blood concentration of prednisolone achieved after a
      dose of 1.5 mg kg-1 are sufficient to suppress monocyte TNF-alpha release and
      cause a biphasic change in peripheral blood monocyte numbers. Suppression of TNF
      alpha is principally a direct glucocorticoid effect, rather than a consequence of
      other prednisolone-induced changes to blood composition.

PMID- 9146851
TI  - An investigation into variability in microvascular skin blood flow and the
      responses to transdermal delivery of acetylcholine at different sites in the
      forearm and hand.
AB  - AIMS: Transdermal iontophoresis in combination with laser Doppler fluxmetry (LDF)
      are useful techniques for examining dermal microcirculatory responses to
      different vasodilators. Differences in skin and microcirculation structure could
      influence the recorded baseline flux, and the observed vasodilatation. To examine
      this we compared baseline flux and the response of microvascular blood flow to a
      single vasodilator, acetylcholine, at sites in the forearm and hand. METHODS:
      Baseline microcirculation flow was recorded by LDF in a temperature controlled
      laboratory. The change in flux with iontophoresis of identical doses of
      acetylcholine, 150 microA for 40 s, was recorded at 12 different sites in the
      forearm and hand in 10 female and 3 male subjects. RESULTS: Baseline flux
      patterns and the vasodilatation to identical periods of iontophoresis of
      acetylcholine were site dependent. Palmar sites showed a higher baseline flux,
      but no vasodilatation to iontophoresis of acetylcholine. In contrast the volar
      forearm, dorsal hand and finger sites showed lower site-dependent baseline flux,
      but did vasodilate. CONCLUSIONS: Patterns of baseline flux are specific to sites
      on the hand and forearm reflecting differences in underlying microvascular
      structure. The vasodilatation to transdermal delivery of acetylcholine is also
      site dependent, but differences in skin structure may be more important than the
      underlying microvasculature in determining the response.

PMID- 9146852
TI  - Increase in force of contraction by activation of the Na+/Ca(2+)-exchanger in
      human myocardium.
AB  - AIMS: The aim of the present study was to investigate whether agents which
      enhance force of contraction via increasing intracellular Na+, i.e. cAMP
      independently, remain effective in failing human myocardium. METHODS: Cumulative
      concentration-response curves with (+/-)BDF 9148 (0.01-10 mumol l-1), a Na(+)
      channel activator, and ouabain (0.01-0.1 mumol l-1), a Na+/K(+)-ATPase inhibitor,
      were performed on electrically driven left ventricular human papillary muscle
      strips (1 Hz, 37 degrees C; dilative cardiomyopathy, NYHA IV, heart
      transplantation, n = 16; nonfailing, donor hearts, n = 5). The beta-adrenoceptor
      agonist isoprenaline (0.001-1 mumol l-1) and Ca2+ (1.8-15 mmol l-1) were studied
      for control. In addition, Ca2+ response curves were obtained on skinned fibre
      preparations from left ventricular myocardium (NYHA IV, n = 7) in the presence of
      BDF 9148 (1 mumol l-1) or a high Na+ concentration (50 mmol l-1) to investigate a
      possible direct or indirect interaction of (+/-)BDF 9148 with the myofilaments.
      RESULTS: While isoprenaline was significantly less effective in increasing force
      of contraction in failing human myocardium than in nonfailing myocardium (P <
      0.01), in NYHA IV, (+/-)BDF 9148 and ouabain were as effective as in nonfailing
      human tissue. In failing and nonfailing myocardium, (+/-)BDF 9148 and ouabain
      exerted positive inotropic effects similar to those of Ca2+. However, the potency
      for (+/-)BDF 9148 to increase force of contraction was higher in NYHA IV than in
      nonfailing human myocardium (P < 0.05). Neither (+/-)BDF 9148 (1 mumol l-1) nor
      an increased concentration of Na+ (50 mmol l-1) altered the Ca2+ sensitivity or
      maximal developed tension of the contractile apparatus in experiments on
      chemically skinned left ventricular fibres. CONCLUSIONS: The enhanced sensitivity
      of the failing human myocardium towards Na(+)-channel modulation is not due to a
      direct or indirect interaction of (+/-)BDF 9148 with cardiac myofilaments but may
      be due to an altered Na(+)-homeostasis in human heart failure.

PMID- 9146853
TI  - Effects of age on cardiovascular responses to adrenaline in man.
AB  - AIMS: Whereas the effects of ageing on beta-receptor mediated responses have been
      extensively studied in vitro and in vivo using the beta-adrenoceptor agonist
      isoprenaline, little is known regarding ageing induced changes in responses to
      endogenous catecholamines. In the present study, we assessed age-related changes
      in cardiac responses to the endogenous beta-adrenoceptor agonist adrenaline and
      the influence of age-related changes in arterial baroreflex function on these
      responses. METHODS: Adrenaline alone was infused in 14 young subjects, age 30 +/-
      2 years (eight males, six females), and 18 older subjects (six males, 12
      females), age 60 +/- 2 years, and together with ganglionic blockade (trimetaphan)
      in seven young and 11 older subjects. Adrenaline was infused at 3-4 incremental
      rates, each rate for 8 min. Cardiac function was assessed by echocardiography.
      RESULTS: Adrenaline alone, at infusion rates 20-160 ng kg-1 min-1 caused similar
      increases in heart rate in the two groups. In contrast, adrenaline caused larger
      increases in stroke volume, ejection fraction, cardiac index and systolic blood
      pressure and larger decreases in end-systolic wall stress and diastolic blood
      pressure in the young compared with older subjects. Older females exhibited the
      smallest increases in stroke volume index and ejection fraction. With concomitant
      ganglionic blockade, all above cardiovascular responses to adrenaline were
      similar in the young and older group. Plasma adrenaline increased similarly in
      the two groups. CONCLUSIONS: We conclude that ganglionic blockade does not unmask
      an age-related decrease in cardiovascular responses to adrenaline (in contrast to
      isoprenaline). A concomitant ageing induced decrease in neuronal uptake (which
      applies to adrenaline, but not isoprenaline) may explain such a differential
      effect.

PMID- 9146854
TI  - In vitro adrenaline and collagen-induced mobilization of platelet calcium and its
      inhibition by naftopidil, doxazosin and nifedipine.
AB  - AIMS: The aim of the study was to obtain further information regarding the modes
      of action of doxazosin, naftopidil and nifedipine on platelet function. METHODS:
      We conducted an in vitro study of drug influences on adrenaline and collagen
      induced mobilization of platelet calcium. RESULTS: In the presence of fibrinogen
      (300 micrograms ml-1) both collagen (5 micrograms ml-1) and adrenaline (16
      microM) stimulated the aggregation of washed platelets. Collagen induced a
      transient rise (+4.97 +/- 0.63 microM) in platelet Ca2+ concentration, [Ca2+]i,
      as measured using the photoprotein aequorin, which coincided with the onset of
      aggregation. Adrenaline induced a smaller rise (+3.6 +/- 0.96 microM) which,
      however, occurred after the onset of aggregation. Naftopidil, an alpha 1
      adrenoreceptor antagonist produced a concentration-dependent inhibition of
      collagen-induced Ca2+ mobilization, maximum inhibition (22.9 +/- 4%, P < 0.05)
      occurring with 40 microM naftopidil. The inhibition of Ca2+ mobilization was not
      reflected by a concentration-dependent inhibition of platelet aggregation,
      although 40 microM naftopidil produced statistically significant inhibition (23.3
      +/- 11.7%, P < 0.05). The adrenaline-induced rise in [Ca2+]i was inhibited dose
      dependently by naftopidil (e.g. 40 microM naftopidil, 100 +/- 0%, P < 0.05), as
      was aggregation (40 microM naftopidil, 100 +/- 0%, P < 0.05). Doxazosin, another
      alpha 1-adrenoreceptor blocker, inhibited Ca2+ mobilization induced by collagen
      to similar extents as for naftopidil (30 microM doxazosin, 17.4 +/- 2.5%, P <
      0.05), but did not inhibit platelet aggregation. It also inhibited the adrenaline
      induced rise in [Ca2+]i in a concentration-dependent manner (30 microM doxazosin,
      37.6 +/- 13.7%, P < 0.05), significant inhibitions of platelet aggregation also
      being produced (30 microM, 49.6 +/- 17.2%, P < 0.05). As expected, the calcium
      channel blocker nifedipine produced concentration-dependent inhibitions of both
      collagen-induced Ca2+ mobilization (e.g. 28 microM nifedipine, 47.8 +/- 2.7%, P <
      0.05) and aggregation (28 microM, 55.1 +/- 9.2%, P < 0.05). CONCLUSIONS: These
      data indicate that the alpha 1-adrenoreceptor blockers, naftopidil and doxazosin,
      inhibit Ca2+ mobilization, this mechanism being possibly the means whereby these
      drugs inhibit platelet aggregation.

PMID- 9146855
TI  - The acute effects of inhaled salbutamol on the beat-to-beat variability of heart
      rate and blood pressure assessed by spectral analysis.
AB  - AIMS: We wanted to study the effects of a 600 micrograms inhaled salbutamol dose
      on the cardiovascular and respiratory autonomic nervous regulation in eight
      children suffering from bronchial asthma. METHODS: In this randomized, double
      blind, placebo-controlled, crossover study we continuously measured
      electrocardiogram, finger systolic arterial pressure (SAP) and flow-volume
      spirometry at baseline as well as 20 min and 2 h after the drug inhalation. The R
      R interval (the time between successive heart beats) and SAP variabilities were
      assessed by using spectral analysis. Baroreflex sensitivity was assessed by using
      cross-spectral analysis. RESULTS: Salbutamol significantly decreased the total
      and low frequency (LF) variability of R-R intervals as well as the high frequency
      (HF) variability of R-R intervals and of SAP. Salbutamol significantly increased
      the LF/HF ratio of R-R intervals and of SAP, minute ventilation, heart rate and
      forced pulmonary function in comparison with placebo. The weight of the subjects
      significantly correlated positively with baroreflex sensitivity and negatively
      with heart rate after the salbutamol inhalation. CONCLUSIONS: We conclude that
      the acute salbutamol inhalation decreases cardiovagal nervous responsiveness,
      increases sympathetic dominance in the cardiovascular autonomic balance, and has
      a tendency to decrease baroreflex sensitivity in addition to improved pulmonary
      function.

PMID- 9146856
TI  - Use of sumatriptan in Denmark in 1994-5: an epidemiological analysis of
      nationwide prescription data.
AB  - AIMS: We describe the use of medication with symptomatic relief of migraine as
      specific indication by analysing prescription data from the entire Danish
      population in 1994 and 1995. METHODS: The data for sumatriptan were analysed at
      the level of the individual user. We used aggregated data for ergotamine drugs.
      RESULTS: Sumatriptan constituted 46% of the total amount of defined daily doses
      (DDD) sold and 94% of the total pharmacy retail price expenses in the drug-group
      studied. In total, 43389 users of sumatriptan were identified who presented
      340148 prescriptions, corresponding to 2.2 million DDD of sumatriptan. The
      quarterly consumption increased by 50% during the study period. Tablets accounted
      for 92% of consumption. The 1 year period prevalence of use of sumatriptan among
      persons 16 years and older was 7.8 per 1000 in 1995 with a female to male
      prevalence ratio of 3.8:1. Use was most common in the age interval 35-54 years.
      Regional differences in use, which were not large, were positively correlated to
      the degree of urbanization. The incidence of use of sumatriptan was estimated at
      3.6 per 1000 person-years. The intensity of use of sumatriptan varied greatly
      with 1.1% of patients (n = 507) using 60 DDD or more within 30 days at some time
      during the observation period. Long-term high use of tablets was common in this
      group. CONCLUSIONS: We conclude that sumatriptan had a considerable impact on the
      treatment of migraine with prescription drugs in Denmark. The underlying reasons
      for high use of the drug in a smaller fraction of the patients deserve further
      study.

PMID- 9146857
TI  - Measurement of total phospholipids in urine of patients treated with gentamicin.
AB  - AIMS: The excretion of phospholipids in urine may be a marker of the early renal
      toxicity of the aminoglycoside antibiotics. Urinary phospholipids are formed in
      myeloid bodies which develop in the lysosomes of proximal tubules during
      treatment with the aminoglycosides, and overflow into the urine. METHODS:
      Published assays were modified in order to measure the total phospholipid
      concentrations in human urine. Phospholipids were extracted from freeze-dried
      urine samples, digested in concentrated sulphuric acid, and the inorganic
      phosphorus content determined by complexing with ammonium molybdate and measuring
      the absorbance at 820 nm. Ten septicaemic patients treated with gentamicin for 5
      7 days had significantly higher urine phospholipid concentrations than 10 healthy
      untreated control subjects (P < 0.0001). There was a negative linear relationship
      between phospholipid excretion and creatinine clearance (r2 = 0.71). RESULTS: In
      34 patients with acute pyelonephritis, increased phospholipid concentrations were
      observed prior to treatment compared with healthy controls (P < 0.001) and did
      not alter during treatment with gentamicin. However, the phospholipid
      concentrations decreased significantly after treatment was completed (P < 0.03).
      CONCLUSIONS: These studies suggest that urinary phospholipids may indicate early
      aminoglycoside toxicity but with poor specificity, as many of the infections
      being treated may themselves be associated with phospholipiduria.

PMID- 9146858
TI  - Stereoselective 4'-hydroxylation of phenytoin: relationship to (S)-mephenytoin
      polymorphism in Japanese.
AB  - AIMS: The aim of this study was to clarify whether phenytoin (PHT)
      stereoselective hydroxylation cosegregates with (S)-mephenytoin phenotype.
      METHODS: A single dose of PHT (100 mg) was administered orally to six healthy
      Japanese subjects in whom the genotype and phenotype of CYP2C19 had been
      determined previously. The urinary excretion profiles of the metabolites of PHT,
      (R)- and (S)-p-HPPH [5-(4-hydroxyphenyl)-5-phenylhydantoin] up to 361 postdose
      were compared between the two groups of poor metabolizers (PMs, n = 3) and
      extensive metabolizers (EMs, n = 3) with respect to CYP2C19. CYP2C9 genotype was
      also determined. RESULTS: All the alleles were found to be wild type (Arg144
      Tyr358Ile359Gly417) in each subject. The mean value for cumulative urinary
      excretion of unchanged PHT was not significantly different between the PMs and
      the EMs. However, recovery of (R)-p-HPPH at 36 h was 3.5-fold lower and that of
      (S)-p-HPPH 1.3-fold lower in PMs than in EMs. Although the mean urinary excretion
      values for both metabolites were significantly lower in the PMs than in the EMs,
      the difference between the two groups was larger for (R)-p-HPPH. A significant
      negative correlation was observed between the hydroxylation index of omeprazole
      (the ratio between the serum concentrations of omeprazole and hydroxyomeprazole
      in blood samples drawn 3 h after drug intake) and the log10 0-12 h urinary
      recovery of (R)-p-HPPH. CONCLUSIONS: In humans, the 4'-hydroxylation of PHT is
      highly stereoselective towards formation of the (S)-enantiomer. Thus, (S)
      hydroxylation by CYP2C9 might be the major determinant of the disposition of PHT.
      However, these results support the hypothesis that the stereoselective
      hydroxylation pathway of PHT to form (R)-p-HPPH cosegregates with the CYP2C19
      metabolic polymorphism.

PMID- 9146859
TI  - Hospitalization for serious blood and skin disorders following use of co
      trimoxazole.
AB  - AIMS: The objective of this study was to quantify the risk of serious blood and
      skin disorders associated with co-trimoxazole. METHODS: We conducted a population
      based cohort study of serious blood and skin disorders requiring hospitalization
      among otherwise healthy users of co-trimoxazole at Group Health Cooperative and
      Puget Sound (GHC). RESULTS: During the years 1987 to 1993 we found six cases of
      co-trimoxazole-associated blood disorders and three cases of co-trimoxazole
      associated skin disorders yielding risks of 5.6/100,000 (95% CI 2.6-12.2) and
      2.8/100,000 (95% CI 0.9-8.2) respectively. In all cases found there was prompt
      recovery after discontinuation of co-trimoxazole. We found no cases of toxic
      epidermal necrolysis. CONCLUSIONS: We conclude that the risk of blood and skin
      disorders associated with the use of co-trimoxazole leading to hospitalization is
      low.

PMID- 9146860
TI  - Ocular safety of anti-ulcer drugs.

PMID- 9146861
TI  - Hospital antibiotic prescribing and feedback.

PMID- 9146862
TI  - Oral cancer: a retrospective study of 100 Danish cases.
AB  - One hundred Danes with oral cancer who were collected consecutively from 1986 to
      1991 were evaluated retrospectively. The study included subjective and objective
      observations in 56% men and in 44% women. M:F ratio was 1.2:1. Fifty percent of
      the patients were non-smokers. Nine percent were women who did not drink alcohol.
      Ten percent of the patients were between 40 and 49 years of age, 20% between 50
      and 59 years, 35% were between 60 and 69 years and 20% between 70 and 79 years of
      age. This may reflect a tradition of early drinking and smoking. Doctor's delay
      was the cause of delayed referral in 14% of the cases while 72% of the patients
      were the cause themselves for the delayed referral.

PMID- 9146863
TI  - Use of buccal fat pad to repair intraoral defects: review of 30 cases.
AB  - The buccal fat pad has been frequently used for the closure of oro-antral and oro
      nasal communications. There are a few studies in the literature reporting its use
      in defects secondary to tumoral resections. In this paper we consider both the
      anatomical basis and the surgical technique. We also review 30 cases, used for
      the repair of 15 defects due to tumoral resections, 8 to maxillary cysts, 6 to
      communications and 1 secondary to a postraumatic defect. It has been successful
      in 28 of the 29 patients, with a complete epithelization of the flap, even in 4
      cases with partial necrosis of the pad. It is an acceptable type of
      reconstruction, versatile and of a simple surgical technique. However, its use is
      limited to small or medium defects, being sometimes scarce.

PMID- 9146864
TI  - A newly developed collagen/silicone bilayer membrane as a mucosal substitute: a
      preliminary report.
AB  - A new bilayer membrane proved effective as a mucosal substitute. The membrane is
      composed of an outer layer of silicone and an inner layer of dehydrothermally
      cross linked composites of fibrillar and denatured collagen sponge. The membrane
      was placed on oral mucosal defects of five patients after operations for cancer.
      Ten to 14 days after application the outer silicone sheet was removed, leaving
      only the inner collagen sponge layer into which cellular tufts of fibroblasts and
      capillaries had infiltrated. The infiltrated collagen matrix became a new
      connective tissue that epithelialised rapidly by migration of peripheral
      epithelium 4-5 weeks after application. In all cases the postoperative course was
      unremarkable and the repair was effective.

PMID- 9146865
TI  - Oral and maxillofacial tumours in children: a review.
AB  - This retrospective review presents our experience of oral and maxillofacial
      tumours in children. The subjects were 250 children under the age of 15 years
      (out of a total of 2747 patients with oral and maxillofacial tumours), who were
      treated after histopathological confirmation of their diagnoses during the 28
      years 1965-92. Diagnosis, incidence, and age at presentation were the main
      outcome measures and the results showed that 232 patients (93%) had benign
      tumours and 18 (7%) were malignant. The most common benign tumour was haemangioma
      (n = 69) and the most common malignant tumour sarcoma (n = 14). The most common
      odontogenic tumour was odontoma (n = 47) and non-odontogenic tumour ossifying
      fibroma (n = 5). The most common site of soft tissue tumours was the tongue (n =
      65) and of bony tumours the mandible (n = 62). About a third of the tumours
      developed in patients between the ages of 6 and 11 years. Most of the angiomas
      developed in patients less than 6 years old, and most of the ameloblastomas in
      those over 12 years of age. Children accounted for 55% of patients with
      lymphangoma, 41% of those with odontoma, and 22% of those with haemangioma. It is
      concluded that most of these lesions were probably developmental malformations
      rather than neoplasms, and that the definition of oral and maxillofacial tumours
      in children should be reconsidered.

PMID- 9146866
TI  - The establishment of a xerostomia clinic: a prospective study.
AB  - The study investigated the aetiological factors and management of patients who
      have xerostomia. The subjects were 100 consecutive patients referred to the Oral
      Medicine Unit for investigation of oral dryness. A detailed case history was
      recorded and patients underwent a systematic examination together with
      sialometry, haematological, biochemical and immunological investigations.
      Suspected cases of Sjogren's syndrome (SS) were referred for assessment by a
      rheumatologist and ophthalmologist. Objective evidence of salivary gland
      hypofunction was found in 39 patients. A definite diagnosis of primary and
      secondary SS was made in 24 and 15 patients respectively, a further five cases
      had possible primary SS. Other causes of xerostomia were: undiagnosed diabetes
      (3); drug-induced (11); therapeutic radiation (3); alcohol-related (3);
      psychogenic (15) and idiopathic (21). Patients complaining of a dry mouth should
      be questioned about non-oral symptoms. In total, 40% of patients attending the
      dry mouth clinic had a diagnosis of SS.

PMID- 9146867
TI  - Early results using a porcine dermal collagen implant as an interpositional
      barrier to prevent recurrent Frey's syndrome.
AB  - Frey's syndrome is a common complication of salivary gland surgery. Although it
      is usually preventable by raising the skin flap in the superficial
      musculoaponeurotic system layer, the treatment of the established condition often
      requires further surgery. There are many surgical options to treat this
      condition. The method described in this paper avoids the morbidity of a second
      operative site by using a biocompatible interpositional layer to prevent the
      sweat glands of the skin being inappropriately cross-innervated. The follow-up
      period on both patients was 12 months. This factor needs to be taken into account
      despite the early improvement observed.

PMID- 9146868
TI  - Stability of bimaxillary osteotomy following surgical correction of class II
      skeletal deformities: a two-centre study.
AB  - This study compares the stability following bimaxillary osteotomy for correction
      of class II skeletal deformities between two groups of patients. One group (15
      patients) were treated at Canniesburn Hospital, West of Scotland Regional Plastic
      and Maxillofacial Unit, UK. The other group (15 patients) were treated at Ann
      Arbor Michigan University Hospital, USA. All cases were treated by Le Fort I
      maxillary advancement/impaction and bilateral sagittal split advancement
      osteotomy. In all cases Le Fort I maxillary osteotomy was more stable than
      sagittal split advancement osteotomy. The maxilla stayed within 1 mm of its
      immediate postoperative position. The average mandibular advancement in
      Canniesburn cases was 6 mm and about 4 mm in Michigan cases. During surgery the
      condyles were displaced about 2 mm posteriorly in Canniesburn cases, but remain
      in their anatomic position in Michigan cases. At 6 months following surgery,
      Canniesburn patients showed a clockwise mandibular relapse. This increased both
      the mandibular plane angle and ramus angle by 2.7 degrees and 2.9 degrees
      respectively. The mandible settled posteriorly 1.7 mm and inferiorly 1.5 mm. In
      Michigan cases the mandible stayed within 1 mm of its immediate postoperative
      position. The difference in mandibular relapse between the two groups was
      statistically significant (P < 0.05). The differences in the stability between
      the two groups are investigated and the theories of mandibular relapse following
      sagittal split osteotomy are discussed.

PMID- 9146869
TI  - Immediate reconstruction of the mandible after resection by sliding osteotomy: a
      new technique.
AB  - A technique of sliding osteotomy is described illustrated by a case for bridging
      mandibular defects of up to 7 cm. The defect is bridged by mobilizing full
      thickness inferior part of the mandibular corpus, and the defect thus produced is
      covered by the advanced outercortex from the ramus. The technique has particular
      advantage in the reconstruction of defects of the para symphysial region.

PMID- 9146870
TI  - Bone grafting of the floor of the maxillary sinus for the placement of endosseous
      implants.
AB  - This study describes and evaluates a technique to augment the floor of the
      maxillary sinus and to widen the alveolar crest of the atrophic posterior maxilla
      with autogenous bone. The subjects were 43 patients whose maxillary alveolar
      crest was not high enough to permit reliable placement of endosseous implants in
      the posterior maxilla. Large autogenous cancellous bone grafts (n = 37) or
      smaller grafts from the mandibular symphyseal area (n = 5) or the maxillary
      tuberosity (n = 1) were harvested. The operations were done in either one stage
      (n = 20 patients, 36 sinuses) or two (bone grafting followed by placement of
      implants, n = 23, 45 sinuses). In 28 cases the sinus membrane was perforated with
      no subsequent problems. Nine of the 171 Branemark implants that were inserted
      were lost during follow-up (mean 26 months, range 8-62 months). Augmentation of
      the maxillary sinus with autogenous bone is a reliable way of achieving placement
      of an implant.

PMID- 9146871
TI  - An audit of antibiotic prescribing in third molar surgery.
AB  - The use of antibiotics as a prophylactic measure against infection is widespread
      following the removal of impacted third molars. The advantages of using such
      prophylaxis appear to be marginal and there is little substantial evidence to
      support the use of second and third generation antibiotics for routine
      prophylaxis. An audit of antibiotic prescribing practices in the University
      Dental Hospital National Health Service Trust (Cardiff) was undertaken and
      demonstrated the potential for saving large sums of money whilst apparently
      incurring no clinical disadvantage. The value of such audit process in oral and
      maxillofacial surgery is in identifying best practice followed by measuring and,
      where possible, improving standards.

PMID- 9146872
TI  - Tissue reaction to three subcutaneously implanted local hemostatic agents.
AB  - Soft tissue response to three subcutaneously implanted local hemostatic agents;
      oxidised regenerated cellulose (Surgicel), gelatin sponge (Spongostan) and
      collagen sponge (Hemostagen) were evaluated histopathologically 7, 14, 21, 30 and
      45 days following their implantation in rats. The results showed that all
      materials were well tolerated by soft tissues. These materials neither seemed to
      impair nor contribute to wound healing.

PMID- 9146873
TI  - The appropriateness of referral of medically compromised dental patients to
      hospital.
AB  - Hospital departments of oral and maxillofacial surgery make a substantial
      contribution to both managing and treating medically-compromised dental patients.
      Contracting arrangements should take account of this. Demographic data suggest
      that the treatment of medically-compromised elderly dentate patients will become
      increasingly important in the General Dental Service (GDS). To determine the
      medical conditions and treatment requirements prompting referral of these
      patients to hospital, a prospective study was undertaken of 75 consecutive adults
      referred for hospital treatment specifically because of a medical condition which
      prevented delivery of routine dental care in the GDS. Patients (mean age: 56
      years) were referred mainly from general medical (33%) and dental (62%)
      practitioners. Cardiovascular disease was the most frequently cited medical
      condition requiring referral (43%; n = 32 cases). Forty-eight patients (64%) were
      symptomatic on presentation and on average had attended on 2.3 occasions before
      definitive treatment was instituted. Fifty-two patients (70%) had no special
      treatment requirements other than those available in the GDS, 11 patients (15%)
      simply required antibiotic prophylaxis and 81% were treated by undergraduates or
      junior staff. These data suggest that many patients referred for dental hospital
      treatment because of underlying medical condition are not in fact medically
      compromised and may be treated in the primary care setting.

PMID- 9146874
TI  - Sagittal ramus split osteotomy: literature review and suggested modification of
      technique.
AB  - The sagittal ramus split osteotomy could be the procedure which defined the
      evolution of the specialty of oral surgery, the art, to the specialty of oral and
      maxillofacial surgery, the science. The basic design of the sagittal ramus split
      surgical procedure evolved very quickly. The elimination of the problems
      encountered has taken longer. Some of these problems are yet to be satisfactorily
      resolved. This paper presents a review of the literature which appears to define
      the evolution of this procedure. With this information in mind, a minor
      modification in the traditional mandibular sagittal ramus technique is presented.
      This modification has proven to be valuable in our hands.

PMID- 9146875
TI  - Needle localisation of the bucco-facial lymph node at surgery.
AB  - A simple method of localizing the bucco-facial lymph node at surgery is
      described, which facilities its excision biopsy.

PMID- 9146876
TI  - Surgery by numbers.

PMID- 9146877
TI  - Specialty centralization.

PMID- 9146878
TI  - Osteoma of the tongue.

PMID- 9146880
TI  - Inhibition of L-type calcium current by propafenone in single myocytes isolated
      from the rabbit atrioventricular node.
AB  - 1. The atrioventricular node (AVN) is an important part of the conduction system
      in the heart and is a significant site of antiarrhythmic drug action. The class 1
      antiarrhythmic propafenone is effective in treating a variety of arrhythmias,
      including those involving the AVN. In this study, we have investigated the
      effects of propafenone on ionic currents in single rabbit AVN cells, focusing in
      particular on those on L-type calcium current (ICa,L). 2. With a standard K-based
      internal dialysis solution, exposure to 5 microM propafenone reduced
      significantly the amplitude of ICa,L. In spontaneously active AVN myocytes,
      action potential upstroke velocity was decreased by propafenone exposure,
      consistent with the observed change in ICa,L. 3. By use of a Cs-based internal
      dialysis solution to record ICa,L selectively, voltage clamp test pulses were
      applied from a holding potential of -40 mV to +10 mV (stimulation frequency 0.33
      Hz). Propafenone 5 microM reduced mean ICa,L density at +10 mV from -9.58 +/-
      1.05 pA/pF to -4.19 +/- 0.60 pA/pF (P < 0.002). A range of propafenone
      concentrations were applied which reduced ICa,L in a dose-dependent manner (IC50
      1.7 microM). When test pulses were applied to a range of potentials, propafenone
      reduced ICa,L at each potential without significantly affecting the activation
      curve for this current. Thus, propafenone reduced ICa,L conductance, without
      affecting the voltage-dependent activation properties of the current. 4. ICa,L
      block by propafenone exhibited tonic-, use- and frequency-dependent
      characteristics. 5. In the presence of propafenone, the voltage-dependence of
      inactivation of ICa,L was shifted 8 mV in the hyperpolarizing direction. Also,
      the recovery of ICa,L from inactivation was slowed by propafenone. 6. The ICa,L
      blocking properties of propafenone may mediate some of the antiarrhythmic
      properties of this agent, particularly in regions of the heart such as the AVN in
      which ICa,L contributes significantly to the action potential upstroke.

PMID- 9146879
TI  - High affinity of sigma 1-binding sites for sterol isomerization inhibitors:
      evidence for a pharmacological relationship with the yeast sterol C8-C7
      isomerase.
AB  - 1. The sigma-drug binding site of guinea-pig liver is carried by a protein which
      shares significant amino acid sequence similarities with the yeast sterol C8-C7
      isomerase (ERG2 protein). Pharmacologically-but not structurally-the sigma 1-site
      is also related to the emopamil binding protein, the mammalian sterol C8-C7
      isomerase. We therefore investigated if sterol C8-C7 isomerase inhibitors are
      high affinity ligands for the (+)-[3H]-pentazocine labelled sigma 1-binding site.
      2. Among the compounds which bound with high affinity to native hepatic and
      cerebral as well as to yeast expressed sigma 1-binding sites were the
      agricultural fungicide fenpropimorph (Ki 0.005 nM), the antihypocholesterinaemic
      drugs triparanol (Ki 7.0 nM), AY-9944 (Ki, 0.46 nM) and MDL28,815 (Ki 0.16 nM),
      the enantiomers of the ovulation inducer clomiphene (Ki 5.5 and 12 nM,
      respectively) and the antioestrogene tamoxifen (Ki 26 nM). 3. Except for
      tamoxifen these affinities are essentially identical with those for the [3H]
      ifenprodil labelled sterol C8-C7 isomerase of S. cerevisiae. This demonstrates
      that sigma 1-binding protein and yeast isomerase are not only structurally but
      also pharmacologically related. Because of its affiliations with yeast and
      mammalian sterol isomerases we propose that the sigma 1-binding site is localized
      on a sterol isomerase related protein, involved in postsqualene sterol
      biosynthesis.

PMID- 9146881
TI  - Simulatory effect of porcine insulin on noradrenaline secretion in guinea-pig
      ileum myenteric nerve terminals.
AB  - 1. The effect of insulin on the release of noradrenaline (NA) from nerve
      terminals was investigated in isolated ileal synaptosomes of guinea-pig. Release
      was determined as the amount of NA, quantified by h.p.l.c.-electrochemical
      detection, from samples incubated with insulin minus that in parallel blanks
      treated with some volume of vehicle. 2. Porcine insulin stimulated the secretion
      of NA in a concentration-dependent manner from 0.01 i.u. ml-1, while the value of
      lactate dehydrogenase in the incubated medium was not influenced by insulin. 3.
      The presence of insulin receptors in this preparation was illustrated by
      immunoblotting with insulin receptor monoclonal antibodies. 4. The release of NA
      by insulin was reduced by guanethidine and bretylium and it was markedly lowered
      in the samples obtained from guinea-pigs that had received an intraperitoneal
      injection of DSP-4, the noradrenergic neurotoxin. 5. Tetrodotoxin attenuated the
      action of insulin at concentrations sufficient to block sodium channels. The
      depolarizing effect of insulin on the membrane potential was also illustrated by
      a concentration-dependent increase in the fluorescence of bisoxonol, a potential
      sensitive dye. 6. The action of insulin was attenuated by removal of calcium
      chloride from the bathing medium. The induction of calcium ion influx by insulin
      into the synaptosomes is supported by the inhibitory effects of the calcium
      channel blockers omega-conotoxin GVIA (for the N-type channels) and nifedipine
      (for the L-type channels). 7. These findings suggest that insulin can stimulate
      NA release from noradrenergic terminals via activation of calcium influx.

PMID- 9146882
TI  - Peptidergic modulation of the sympathetic contraction in the rabbit ear artery:
      effects of temperature.
AB  - 1. The effects of neuropeptide Y, endothelin-1, arginine-vasopressin and
      angiotensin II on the vascular contraction to sympathetic nerve stimulation were
      studied in isolated segments, 2 mm long, from the rabbit central ear artery, a
      cutaneous vessel, during changes in temperature (24 degrees -41 degrees C). 2.
      Transmural electrical stimulation (1-8 Hz, at supramaximal voltage) produced
      frequency-dependent contraction, and this response, partially blocked by
      tetrodotoxin (1 microM) and phentolamine (1 microM), was reduced by cooling (30
      degrees C -24 degrees C) and was not modified by warming (41 degrees C), as
      compared to that recorded at 37 degrees C. 3. Pretreatment with neuropeptide Y
      (10, 30 and 100 nM) increased in a concentration-dependent manner the vascular
      contraction to sympathetic stimulation at every temperature studied, but this
      potentiation was greater during cooling (34 degrees C -24 degrees C) than at 37
      degrees C or warming (41 degrees C). 4. Pretreatment with endothelin-1 (3 and 10
      nM) or vasopressin (0.1, 0.3 and 1 nM) increased in a concentration-dependent
      manner the vascular contraction to sympathetic stimulation during cooling (34
      degrees C -24 degrees C), but not at 37 degrees C or warming (41 degrees C). 5.
      Pretreatment with angiotensin II (0.1, 0.3 and 1 microM) did not modify the
      contraction to sympathetic stimulation at any temperature studied. 6. These
      results suggest that neuropeptide Y, endothelin-1 and vasopressin, but not
      angiotensin II, modulate the cutaneous vasoconstriction to sympathetic nerve
      stimulation by potentiating this vasoconstriction during cooling.

PMID- 9146883
TI  - Tachykinin regulation of basal synovial blood flow.
AB  - 1. Experiments were performed to investigate the role of endogenously released
      tachykinins in the regulation of blood flow to the rat knee joint. Synovial
      perfusion was assessed by laser Doppler perfusion imaging, which permitted
      spatial measurement of relative changes in perfusion from control (pre drug
      administration), expressed as the percentage change. Most experiments were
      performed on the exposed medial aspect of the knee joint capsule. 2. Neither the
      selective tachykinin NK1 receptor antagonist, FK888, nor the selective tachykinin
      NK2 receptor antagonist, SR48968, significantly influenced synovial blood flow at
      doses of 10(-12), 10(-10) and 10(-8) mol. However, topical co-administration of
      these agents produced significant dose-dependent reductions in basal synovial
      perfusion of 6.3 +/- 4.6 and 12.0 +/- 3.4 and 19.9 +/- 2.6%, respectively; n =
      29. The non-selective tachykinin NK1/NK2 receptor antagonist, FK224, also
      produced significant (at 10(-10) and 10(-8) mol), but less potent, reductions in
      perfusion of 5.3 +/- 4.0, 8.4 +/- 2.2 and 5.9 +/- 2.8%, respectively; n = 25. 3.
      Topical administration of the alpha 1-, alpha 2-adrenoceptor antagonist
      phenoxybenzamine elicited a 31.3 +/- 6.2% increase in blood flow which was
      substantially reduced to 10.4 +/- 3.8% by co-administration of the FK888 and
      SR48968 (both at 10(-8) mol; n = 8-13), suggesting that normally there is
      sympathetic vasoconstrictor "tone' which is opposed by the vasodilator action of
      endogenous tachykinins. 4. One week after surgical interruption of the nerve
      supply to the knee joint, co-administration of FK888 and SR48968 (both at 10(-8)
      mol) now produced slight vasodilatation (6.7 +/- 4.6%; n = 9) which did not
      differ significantly from vehicle treatment. Depletion of tachykinins from
      sensory nerve fibres by systemic capsaicin administration also resulted in
      abolition of the vasoconstrictor effect of FK888 and SR48968 (both at 10(-8)
      mol), with these agents only producing a slight vasodilatation (2.5 +/- 5.3%; n =
      6). 5. By use of a near infra-red laser source it was possible to image knee
      joint perfusion transcutaneously, the overlying skin being left intact. In this
      more physiological situation, close intra-arterial injection of the combination
      of FK888 and SR48968 (both at 10(-8) mol) again elicited vasoconstriction (48.8
      +/- 16.2% reduction in blood flow; n = 4). 6. These results indicate that
      endogenous tachykinins may be continuously released from sensory fibers
      innervating the joint. Basal release of tachykinins could therefore be an
      important physiological influence opposing sympathetic vasoconstrictor tone.

PMID- 9146884
TI  - Modulation of the pressor response elicited by carbachol and electrical
      stimulation of the amygdala by muscarinic antagonists in conscious rats.
AB  - 1. The nature of the muscarinic receptor involved in mediating cardiovascular
      changes caused by unilateral microinjection of carbachol (5 nmol) into, and
      electrical stimulation (200-300 microA) of, the amygdaloid complex was
      investigated in conscious, unrestrained female Sprague-Dawley rats. 2. Unilateral
      microinjection of carbachol (5 nmol; n = 6) and electrical stimulation (200-300
      microA, 80 Hz, 30 s; n = 4) caused a significant rise in blood pressure of 21 +/-
      4 mmHg and 25 +/- 5 mmHg, respectively. These changes were associated with no
      overall effect on heart rate. The effects of electrical stimulation were found to
      be repeatable. 3. Pretreatment i.c.v. with pirenzepine (5-20 mmol; n = 6-7 for
      each dose), dose-dependently inhibited the rise in blood pressure induced by
      carbachol, whereas AF-DX 116 (100 nmol; n = 6) failed to have any effect on the
      carbachol-induced pressure response. Neither antagonist alone had any effect on
      resting baseline variables. 4. Unilateral microinjections of atropine sulphate (1
      100 nmol; n = 4-6 for each dose), pirenzepine (0.03-10 nmol; n = 4 for each dose)
      or AF-DX 116 (10-60 nmol; n = 4-5 for each dose), into the amygdala, dose
      dependently inhibited the rise in blood pressure caused by electrical stimulation
      (200-300 microA). The ID50 values were 1.05, 0.23 and 39.5 nmol, respectively.
      Although pirenzepine seemed to be more potent than atropine, this difference was
      not significant. 5. It is concluded that the rise in blood pressure elicited by
      unilateral microinjection of carbachol into, or electrical stimulation of, the
      amygdaloid complex is mediated by M1-muscarinic receptors.

PMID- 9146885
TI  - Role of endothelium and nitric oxide in histamine-induced responses in human
      cranial arteries and detection of mRNA encoding H1- and H2-receptors by RT-PCR.
AB  - 1. Histamine induces relaxation of human cranial arteries. Studies have revealed
      that the relaxant histamine H1-receptor predominates in human cerebral and the H2
      receptor in temporal arteries, while H1- and H2-receptors are of equal importance
      in the middle meningeal artery. The purpose of the present study was to examine
      the role of the endothelium and nitric oxide in histamine-induced responses and
      to show the presence of mRNA encoding H1- and H2-receptors in human cranial
      arteries. 2. Electrophoresis of polymerase chain reaction (PCR) products from
      human cerebral, middle meningeal and temporal arteries, demonstrated products
      corresponding to mRNA encoding both H1- and H2-receptors in arteries with and
      without endothelium. The amplified PCR products were sequenced and showed 100%
      homology with the published sequences of these histamine receptors. 3. A
      sensitive in vitro system was used to study vasomotor responses to histamine. In
      precontracted cerebral, middle meningeal and temporal arteries with and without
      endothelium, histamine caused a concentration-dependent relaxation with Imax
      values between 87% and 81% and pIC50 values between 8.14 and 7.15. In arteries
      without endothelium the histamine-induced relaxation was significantly less
      potent (Imax values between 87% and 66% and pIC50 values between 7.01 and 6.67)
      than in cranial arteries with an intact endothelium. 4. This addition of
      histamine to arteries without endothelium and pretreated with the histamine H2
      antagonist, cimetidine (10(-5) M), caused a concentration-dependent contraction
      of the cranial arteries with Emax values between 86% and 29% and pEC50 values
      between 7.53 and 6.77. This contraction was blocked by the histamine H1-receptor
      antagonist, mepyramine (10(-7) M), and even turned into a relaxation with Imax
      values between 84% and 14% and pIC50 values between 7.42 and 5.86. 5. The nitric
      oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 3 x 10(-5) M)
      significantly inhibited the relaxant response to histamine in cerebral and
      temporal arteries (pIC50 values between 7.43 and 7.13). The combined treatment
      with L-NAME (3 x 10(-5) M) and cimetidine (10(-5) M) caused a further
      displacement of the concentration-response curve (pIC50 values between 7.14 and
      6.57) and decreased the maximum relaxant responses in all three cranial arteries
      (Imax values between 62% and 39%). 6. In conclusion, this is the first study
      which show mRNA encoding histamine H1- and H2-receptors in human cranial
      arteries. The results indicate that histamine-induced relaxation of human cranial
      arteries is partially mediated via an endothelial H1-receptor coupled to the
      production of nitric oxide and partially via a H2-receptor associated with the
      smooth muscle cells. In addition, there is evidence for a contractile H1-receptor
      in the smooth muscle cells in these arteries.

PMID- 9146886
TI  - Cerebrovascular effects of nitric oxide manipulation in spontaneously
      hypertensive rats.
AB  - 1. Evidence that nitric oxide (NO) bioactivity is altered in chronic hypertension
      is conflicting, possibly as a result of heterogeneity in both the nature of the
      dysfunction and in the disease process itself. The brain is particularly
      vulnerable to the vascular complications of chronic hypertension, and the aim of
      this study was to assess whether differences in the cerebrovascular
      responsiveness to the NO synthase (NOS) inhibitors, NG-nitro-L-arginine methyl
      ester (L-NAME) and 7-nitroindazole (7-NI), and to the NO donor 3
      morpholinosydnonimine (SIN-1) might indicate one possible source of these
      complications. 2. Conscious spontaneously hypertensive (SHR) and WKY rats, were
      treated with L-NAME (30 mg kg-1, i.v.), 7-NI (25 mg kg-1, i.p.), (0.54 or 1.8 mg
      kg-1 h-1, continuous i.v. infusion) or saline (i.v.), 20 min before the
      measurement of local cerebral blood flow (LCBF) by the fully quantitative [14C]
      iodoantipyrine autoradiographic technique. 3. With the exception of mean arterial
      blood pressure (MABP), there were no significant differences in physiological
      parameters between SHR and WKY rats within any of the treatment groups, or
      between treatment groups. L-NAME treatment increased MABP by 27% in WKY and 18%
      in SHR groups, whilst 7-NI had no significant effect in either group. Following
      the lower dose of SIN-1 infusion, MABP was decreased to a similar extent in both
      groups (around -20%). There was no significant difference in MABP between groups
      following the higher dose of SIN-1, but this represented a decrease of -41% in
      SHR and -21% in WKY rats. 4. With the exception of one brain region (nucleus
      accumbens), there were no significant differences in basal LCBF between WKY and
      SHR. L-NAME produced similar decreases in LCBF in both groups, ranging between 
      10 and -40%. The effect of 7-NI upon LCBF was more pronounced in the SHR (ranging
      from -34 to -57%) compared with the WKY (ranging from -14 to -43%), and in seven
      out of the thirteen brain areas examined there were significant differences in
      LCBF. 5. Following the lower dose of SIN-1, in the WKY 8 out of the 13 brain
      areas examined showed significant increases in blood flow compared to the saline
      treated animals. In contrast, only 2 brain areas showed significant increases in
      flow in the SHR. In the rest of the brain areas examined the effects of SIN-1
      upon LCBF were less marked than in the WKY. 6. Infusion of the higher dose of SIN
      1 resulted in further significant increases in LCBF in the WKY group (ranging
      between +30% and +74% compared to saline-treated animals), but no significant
      effects upon LCBF were found in the SHR. As a result, there were significant
      differences in LCBF between SIN-1-treated WKY and SHR in six brain areas. In most
      brain areas examined, cerebral blood flow in SHR following the higher dose of SIN
      1 was less than that measured with the lower dose of SIN-1. 7. Despite comparable
      reductions in MABP (approximately 20%) in both groups, calculated cerebrovascular
      resistance (CVR) confirmed that the vasodilator effects of the lower dose of SIN
      1 were significantly more pronounced throughout the brain in the WKY (ranging
      between -3% and -50%; median = -38%) when compared to the SHR (ranging between 
      10% and -36%; median = -26%). In the animals treated with the higher dose of SIN
      1, CVR changes were broadly similar in both groups (median = -45% in WKY and -42%
      in SHR), but with the reduction in MABP in SHR being twice that found in WKY,
      this is in keeping with an attenuated blood flow response to SIN-1 in the SHR. 8.
      The results of this study indicate that NO-dependent vasodilator capacity is
      reduced in the cerebrovasculature of SHR. In addition, the equal responsiveness
      to a non-specific NOS inhibitor but an enhanced effectiveness of a specific
      neuronal NO inhibitor upon LCBF in the SHR could be consistent with an
      upregulation of the neuronal NO system.

PMID- 9146887
TI  - The interaction of diadenosine polyphosphates with P2x-receptors in the guinea
      pig isolated vas deferens.
AB  - 1. The site(s) at which diadenosine 5',5"'-P1,P4-tetraphosphate (AP4A) and
      diadenosine 5', 5"'-P1,P5-pentaphosphate (AP5A) act to evoke contraction of the
      guinea-pig isolated vas deferens was studied by use of a series of P2-receptor
      antagonists and the ecto-ATPase inhibitor 6-N,N-diethyl-D-beta,gamma
      dibromomethyleneATP (ARL 67156). 2. Pyridoxalphosphate-6-azophenyl-2',4'
      disulphonic acid (PPADS) (300 nM - 30 microM), suramin (3-100 microM) and
      pyridoxal-5'-phosphate (P-5-P) (3-1000 microM) inhibited contractions evoked by
      equi-effective concentrations of AP5A (3 microM), AP4A (30 microM) and alpha,beta
      methyleneATP (alpha,beta-meATP) (1 microM), in a concentration-dependent manner
      and abolished them at the highest concentrations used. 3. PPADS was more potent
      than suramin, which in turn was more potent than P-5-P. PPADS inhibited AP5A,
      AP4A and alpha,beta-meATP with similar IC50 values. No significant difference was
      found between IC50 values for suramin against alpha,beta-meATP and AP5A or
      alpha,beta-meATP and AP4A, but suramin was more than 2.5 times more potent
      against AP4A than AP5A. P-5-P showed the same pattern of antagonism. 4.
      Desensitization of the P2xi-receptor by alpha,beta-meATP abolished contractions
      evoked by AP5A (3 microM) and AP4A (30 microM), but had no effect on those
      elicited by noradrenaline (100 microM). 5. ARL 67156 (100 microM) reversibly
      potentiated contractions evoked by AP4A (30 microM) by 61%, but caused a small,
      significant decrease in the mean response to AP5A (3 microM). 6. It is concluded
      that AP4A and AP5A act at the P2xi-receptor, or a site similar to the P2xi
      receptor, to evoke contraction of the guinea-pig isolated vas deferens.
      Furthermore, the potency of AP4A, but not AP5A, appears to be inhibited by an
      ecto-enzyme which is sensitive to ARL 67156.

PMID- 9146888
TI  - Inhibition by singlet molecular oxygen of the vascular reactivity in rabbit
      mesenteric artery.
AB  - 1. The effects of reactive oxygen intermediates derived from photoactivated rose
      bengal on the vascular reactivity have been evaluated in rabbit mesenteric artery
      ring preparations. The artery rings were exposed to xanthene dye rose bengal (50
      nM) illuminated (6,000 lux) at 560 nm for 30 min. Spin trapping studies with
      2,2,6,6-tetramethylpiperidine (TEMP) and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO)
      with electron spin resonance spectrometry were also conducted in solution (and
      not within tissues) to determine quantitatively the reactive oxygen species
      generated from photoactivated rose bengal. 2. Contraction of the ring
      preparations induced by noradrenaline (10(-8) to 10(-4) M) was attenuated by
      previous exposure to photolysed rose bengal; the observation that the pD2
      decreased without a significant reduction in maximum tension generation is
      consistent with the view that receptor dysfunction may be involved in the effect
      of photolysed rose bengal. 3. Prior exposure to photolysed rose bengal of the
      ring preparations inhibited the endothelium-dependent relaxation evoked by
      acetylcholine (10(-6) M) and calcium ionophore A23187 (10(-7) M), but not the
      endothelium-independent relaxation evoked by nitroglycerin (10(-6) M). 4. A
      variety of scavengers, superoxide dismutase (33 units ml-1), catalase (32 units
      ml-1) and 1,3-dimethyl-2-thiourea (DMTU, 10 mM), which should eliminate the
      superoxide anion radical, H2O2 and the hydroxyl radical, had no effect on the
      attenuated responses to noradrenaline and acetylcholine induced by photolysed
      rose bengal. In contrast, the inhibition of the observed effect of photolysed
      rose bengal was obtained with addition of histidine (25 mM), a singlet molecular
      oxygen quencher. 5. It was found that photolysis of rose bengal from a 1:2:2:1
      quartet, characteristic of the hydroxyl radical-DMPO spin adduct, which was
      effectively blunted by DMTU, superoxide dismutase and catalase whereas histidine
      was ineffective. The results of the electron spin resonance study also showed
      that a singlet molecular oxygen was produced by photoactivation of rose bengal;
      this was detected as singlet oxygen-TEMP product (TEMPO; 2,2,6,6
      tetramethylpiperidine-N-oxyl). The formation of the TEMPO signal was strongly
      inhibited by histidine, but not by DMTU, superoxide dismutase and catalase. 6. It
      is suggested that the superoxide anion radical, H2O2 and hydroxyl radical are
      formed in addition to singlet molecular oxygen, and the data obtained from the
      present study indicate that singlet molecular oxygen is one of the most
      destructive oxygen species. Endothelium-dependent relaxation is quite vulnerable
      to singlet molecular oxygen. Singlet oxygen also depresses noradrenaline-induced
      contraction possibly via alpha-adrenoceptor dysfunction. This, in turn, may lead
      to vascular incompetence.

PMID- 9146889
TI  - Measurement of GABAA receptor function in rat cultured cerebellar granule cells
      by the Cytosensor microphysiometer.
AB  - 1. gamma-Aminobutyric acid (GABA), acting via the GABAA receptor, increased the
      extracellular acidification rate of rat primary cultured cerebellar granule
      cells, measured by the Cytosensor microphysiometer. 2. The optimal conditions for
      the measurement of GABAA receptor function in cerebellar granule cells by
      microphysiometry were: cells seeded at 9-12 x 10(5) cells/transwell cup and
      maintained in vitro for 8 days, GABA stimulation performed at 25 degrees C, with
      a stimulation time of 33 s. 3. GABA stimulated a concentration-dependent increase
      in the extracellular acidification rate with an EC50 of 2.0 +/- 0.2 microM (mean
      +/- s.e.mean, n = 7 experiments) and maximal increase (Emax) over basal response
      of 15.4 +/- 1.2%. 4. The sub-maximal GABA-stimulated increase in acidification
      rate could be potentiated by the 1,4-benzodiazepine, flunitrazepam (100 nM). The
      10 nM GABA response showed the maximal benzodiazepine facilitation (GABA alone,
      1.4 microV s-1, GABA + flunitrazepam, 3.8 microV s-1, mean increment over basal,
      n = 7). 5. The GABA-stimulated increase in acidification rate was inhibited by
      the GABAA antagonist, bicuculline (100 microM) (90% inhibition at 1 mM GABA). 6.
      The results of this study show that activation of GABAA receptors in rat
      cerebellar granule cells caused an increase in the extracellular acidification
      rate; an effect which was potentiated by benzodiazepines and inhibited by a GABAA
      receptor antagonist. This paper defines the conditions and confirms the
      feasibility of using microphysiometry to investigate GABAA receptor function in
      primary cultured CNS neurones. The microphysiometer provides a rapid and
      sensitive technique to investigate the regulation of the GABAA receptor in
      populations of neurones.

PMID- 9146890
TI  - Characterization of the prostanoid receptors mediating inhibition of PAF-induced
      aggregation of guinea-pig eosinophils.
AB  - 1. Prostanoids induce a wide range of biological actions which are mediated by
      specific membrane-bound receptors. We have recently shown that the E-type
      prostaglandins, PGE1 and PGE2, effectively inhibit eosinophil aggregation induced
      by platelet-activating factor (PAF). In an attempt to determine which prostanoid
      receptor(s) were involved, we investigated the effects of a range of selective
      prostanoid agonists and antagonists on eosinophil homotypic aggregation induced
      by PAF. 2. Both PGE1 and PGE2 (10(-10) to 10(-6) M) induced a concentration
      related inhibition of the aggregation response induced by PAF. PGE1 was more
      effective than PGE2 but PGE2 was slightly more potent than PGE1 (approximate IC50
      values for PGE1 and PGE2 of 1.5 x 10(-8) M and 5 x 10(-9) M, respectively). 3.
      The EP2-selective agonists, 11-deoxy-PGE1, butaprost and AH13205, and the EP2/EP3
      selective agonist, misoprostol, also inhibited PAF-induced aggregation. The rank
      order of potency for EP2-selective agonists was 11-deoxy-PGE1 > misoprostol >
      butaprost = AH13205. The protein kinase A inhibitor, KT5720 (10(-6) M), reversed
      the inhibitory effects of 11-deoxy-PGE1 (10(-6) M) and AH13205 (10(-5) M). 4. The
      EP1/EP3-selective agonist, sulprostone, and the EP1-selective agonist, 17-phenyl
      omega-trinor PGE2, had no significant inhibitory activity when tested at
      concentrations up to 10(-6) M. The EP4-receptor antagonist, AH23848B, had no
      effect on PAF-induced aggregation and did affect the inhibitory activity of PGE1.
      5. The IP-selective agonist, cicaprost (up to 10(-6) M), and the IP/EP1-receptor
      agonist, iloprost (up to 10(-5) M), had no significant effect on PAF-induced
      eosinophil aggregation. However, iloprost significantly augmented the inhibitory
      effects of a maximally inhibitory concentration of PGE2. 6. PGD2 (10(-5) M) had
      no effect on eosinophil aggregation and the inhibitory activity of PGE1 on PAF
      induced eosinophil aggregation was not altered by the DP-selective receptor
      antagonist, BWA868C. 7. The results presented here suggest that the inhibition of
      PAF-induced eosinophil aggregation by prostanoids is mediated by the occupation
      of EP2-receptors. It is important to note that the effects of naturally occurring
      prostanoids, such as PGE2, on eosinophil aggregation occur at low concentrations
      highlighting a potential role for EP2 receptors in regulating eosinophil function
      in vivo.

PMID- 9146892
TI  - Characterization of human recombinant somatostatin sst5 receptors mediating
      activation of phosphoinositide metabolism.
AB  - 1. We have functionally characterized the human recombinant somatostatin (SRIF)
      sst5 receptor in Chinese hamster ovary-K1 (CHOsst5) cells by measuring total [3H]
      inositol phosphate ([3H]-InsPx) accumulation, in the presence of 10 mM LiCl, in
      cells labelled with [3H]-myo-inositol. 2. In CHOsst5 cells, SRIF, SRIF-28 and the
      cyclic hexapeptide, L-362,855, produced time- and concentration-related increases
      in [3H]-InsPx accumulation, with similar potency (pEC50 values of 6.5, 6.8 and
      7.2, respectively). L-362,855 behaved as a partial agonist, producing
      approximately 30% of the SRIF maximum response. The other peptide analogues of
      SRIF, BIM-23027 and BIM-23056, were inactive as agonists. 3. Increasing
      concentrations of L-362,855 increased [3H]-InsPx accumulation and simultaneously
      produced rightward shifts of SRIF concentration-effect curves, with an estimated
      pKp value of 7.6, confirming that it was acting as a partial agonist. 4. BIM
      23056, but not BIM-23027, potently antagonized SRIF-induced [3H]-InsPx
      accumulation, with an estimated pKB value of 7.4. BIM-23056 did not antagonize
      [3H]-InsPx accumulation induced by uridine 5'-triphosphate (UTP). 5. SRIF- but
      not UTP-induced [3H]-InsPx accumulation was inhibited by increasing
      concentrations of pertussis toxin (0.01-100 ng ml-1), indicating the involvement
      of pertussis toxin-sensitive G-proteins. 6. These findings show that the human
      recombinant sst5 receptor, when stably expressed in CHO-K1 cells, is able to
      mediate activation of phosphoinositide metabolism in a pertussis toxin-sensitive
      manner. In this system L-362,855 behaved as a partial agonist while BIM-23056 was
      a specific antagonist. These agents should provide useful tools for functionally
      characterizing endogenous SRIF receptors.

PMID- 9146891
TI  - Alteration of flow-induced dilatation in mesenteric resistance arteries of L-NAME
      treated rats and its partial association with induction of cyclo-oxygenase-2.
AB  - 1. We investigated the response to pressure (myogenic tone) and flow of rat
      mesenteric resistance arteries cannulated in an arteriograph which allowed the
      measurement of intraluminal diameter for controlled pressures and flows. Rats
      were treated for 3 weeks with NG-nitro-L-arginine methyl ester (L-NAME, 50 mg kg
      1 day-1) or L-NAME plus the angiotensin I converting enzyme inhibitor (ACEI)
      quinapril (10 mg kg-1 day-1). 2. Mean blood pressure increased significantly in
      chronic L-NAME-treated rats (155 +/- 4 mmHg, n = 8, vs control 121 +/- 6 mmHg, n
      = 10; P < 0.05). L-NAME-treated rats excreted significantly more dinor-6-keto
      prostaglandin F1 alpha (dinor-6-keto PGF1 alpha), the stable urinary metabolite
      of prostacyclin, than control rats. The ACEI prevented the rise in blood pressure
      and the rise in urinary dinor-6-keto PGF1 alpha due to L-NAME. 3. Isolated
      mesenteric resistance arteries, developed myogenic tone in response to stepwise
      increases in pressure (42 +/- 6 to 847 +/- 10 mN mm-1, from 25 to 150 mmHg, n =
      9). Myogenic tone was not significantly affected by the chronic treatment with L
      NAME or L-NAME + ACEI. 4. Flow (100 microliters min-1) significantly attenuated
      myogenic tone by 50 +/- 6% at 150 mmHg (n = 10). Flow-induced dilatation was
      significantly attenuated by chronic L-NAME to 22 +/- 6% at 150 mmHg (n = 10, p =
      0.0001) and was not affected in the L-NAME + ACEI group. 5. Acute in vitro NG
      nitro-L-arginine (L-NOARG, 10 microM) significantly decreased flow-induced
      dilation in control but not in L-NAME or L-NAME + ACEI rats. Both acute
      indomethacin (10 microM) and acute NS 398 (cyclo-oxygenase-2 (COX-2) inhibitor, 1
      microM) did not change significantly flow-induced dilatation in controls but they
      both decreased flow-induced dilatation in the L-NAME and L-NAME + ACEI groups.
      Acute Hoe 140 (bradykinin receptor inhibitor, 1 microM) induced a significant
      contraction of the isolated mesenteric arteries which was the same in the 3
      groups. 6. Immunofluorescence analysis of COX-2 showed that the enzyme was
      expressed in resistance mesenteric arteries in L-NAME and L-NAME + ACEI groups
      but not in control. COX-1 expression was identical in all 3 groups. 7. We
      conclude that chronic inhibition of nitric oxide synthesis is associated with a
      decreased flow-induced dilatation in resistance mesenteric arteries which was
      compensated by an overproduction of vasodilator prostaglandins resulting in part
      from COX-2 expression. The decrease in flow-induced dilatation was prevented by
      the ACEI, quinapril.

PMID- 9146893
TI  - A novel murine model of allergic inflammation to study the effect of
      dexamethasone on eosinophil recruitment.
AB  - 1. We have developed a novel model of allergen-induced eosinophil into mouse air
      pouches following sensitization and challenge with ovalbumin (Ova). This model
      was used to investigate the mechanism(s) underlying the anti-inflammatory action
      of the glucocorticoid hormone dexamethasone (Dex). 2. Injection of 10 micrograms
      Ova into 6-day-old dorsal air-pouches of mice sensitized to the same antigen
      provoked an intense cell accumulation as early as 6 h post-challenge (0.08 +/-
      0.03 and 4.0 +/- 1.0 x 10(5) leucocytes in saline and Ova-treated air-pouches,
      respectively), maximal at 24 h (0.02 +/- 0.01 and 6.0 +/- 0.8 x 10(5) leucocytes
      in saline and Ova-treated air-pouches, respectively) and persisted up to 48 h. At
      the 24 h time-point, the cellular infiltrate consisted of 37% eosinophils, 18%
      neutrophils and 45% mononuclear cells, as assessed by histological examination.
      The same ratio of eosinophil/neutrophil was obtained by fluorescence-activated
      cell sorting (FACS) analysis, since 72% of the polymorphonuclear (PMN) population
      was positive for very-late antigen-4 (VLA-4) expression. 3. Subcutaneous (s.c.)
      administration of Dex (50 or 100 micrograms per mouse, -1 h) inhibited eosinophil
      accumulation into Ova challenged air-pouches by about 70% (P < 0.05) and 75% (P <
      0.05), respectively, when compared to controls. Cell accumulation measured at 48
      h after Ova injection was also significantly reduced (-75%) by Dex administration
      at the 24 h time-point (n = 12, P < 0.05). 4. Eosinophil numbers in the bone
      marrow and blood were quantitated. We found that the sensitization protocol
      induced a 3 fold increase in eosinophil numbers in the bone marrow (naive mice:
      2.7 +/- 0.3 x 10(5); sensitized mice: 8.7 +/- 1.7 x 10(5), P < 0.05) and blood
      (naive mice: 0.5 +/- 0.2 x 10(5); sensitized mice: 1.5 +/- 0.3 x 10(5), P <
      0.01). However, 24 h following Ova challenge, the eosinophil numbers in the bone
      marrow had dropped (3.7 +/- 0.8 x 10(5) with no change in the circulating pool,
      suggesting an equilibrium within the eosinophil pools had been reached. 5. Dex
      administration provoked a profound eosinopaenia in the blood of naive (5.2 +/-
      1.5 to 0.9 +/- 0.6 x 10(4)) and sensitized mice (1.5 +/- 0.3 to 0.08 +/- 0.02 x
      10(5)) at 4 h. This effect was reversed within 24 h. Dex also inhibited the
      release of eosinophils from the bone marrow in response to Ova challenge. 6. We
      show for the first time that express the steroid-inducible protein lipocortin 1
      (LC1). FACS analysis of eosinophils emigrated into the Ova challenged air-pouches
      revealed detectable LC1-like immunoreactivity (373 x 10(3)). These data were also
      substantiated by LC1 detection in circulating eosinophils of interleukin-5
      transgenic mice (strain: CBA/Ca). However, s.c. injection of Dex (50 micrograms)
      did not alter LC1 levels in blood eosinophils, such that 235 +/- 21 x 10(3) LC1
      like molecules per cell were measured after vehicle treatment (n = 5), and 224 +/
      8 x 10(3) LC1-like molecules per cell were associated with this cell type 1 h
      after steroid treatment (n = 5, not significant). Finally, resident eosinophils
      (in the pleural cavity) were found to have much higher LC1 levels than that found
      in the blood circulation (2 fold increase, P < 0.05). 7. Passive immunization of
      mice against LC1 with a validated antiserum (termed LCS3) and protocol failed to
      modify the anti-migratory activity exerted by Dex towards eosinophil
      extravasation into Ova-challenged air-pouches. The steroid (50 micrograms s.c., 
      1 h) produced a similar degree of inhibition of eosinophil accumulation both in
      control animals (treated with a non-immune sheep serum) the LCS3-treated mice (
      56% and 59%, respectively, n = 15-21, not significant). 8. In conclusion, the air
      pouch provides a novel and convenient cavity to study allergen-induced cell
      recruitment which is sensitive to glucocorticoid hormone treatment. The effect of
      Dex on eosinophil distribution in these experimental conditions has been studied
      in detail and

PMID- 9146894
TI  - Biochemical and pharmacological profile of a tetrasubstituted furanone as a
      highly selective COX-2 inhibitor.
AB  - 1. DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furan
      one) was identified as a novel orally active and highly selective cyclo-oxygenase
      2 (COX-2) inhibitor. 2. In CHO cells stably transfected with human COX isozymes,
      DFU inhibited the arachidonic acid-dependent production of prostaglandin E2
      (PGE2) with at least a 1,000 fold selectivity for COX-2 (IC50 = 41 +/- 14 nM)
      over COX-1 (IC50 > 50 microM). Indomethacin was a potent inhibitor of both COX-1
      (IC50 = 18 +/- 3 nM) and COX-2 (IC50 = 26 +/- 6 nM) under the same assay
      conditions. The large increase in selectivity of DFU over indomethacin was also
      observed in COX-1 mediated production of thromboxane B2 (TXB2) by Ca2+ ionophore
      challenged human platelets (IC50 > 50 microM and 4.1 +/- 1.7 nM, respectively).
      3. DFU caused a time-dependent inhibition of purified recombinant human COX-2
      with a Ki, value of 140 +/- 68 microM for the initial reversible binding to
      enzyme and a kappa 2 value of 0.11 +/- 0.06 s-1 for the first order rate constant
      for formation of a tightly bound enzyme-inhibitor complex. Comparable values of
      62 +/- 26 microM and 0.06 +/- 0.01 s-1, respectively, were obtained for
      indomethacin. The enzyme-inhibitor complex was found to have a 1:1 stoichiometry
      and to dissociate only very slowly (t1/2 = 1-3 h) with recovery of intact
      inhibitor and active enzyme. The time-dependent inhibition by DFU was decreased
      by co-incubation with arachidonic acid under non-turnover conditions, consistent
      with reversible competitive inhibition at the COX active site. 4. Inhibition of
      purified recombinant human COX-1 by DFU was very weak and observed only at low
      concentrations of substrate (IC50 = 63 +/- 5 microM at 0.1 microM arachidonic
      acid). In contrast to COX-2, inhibition was time-independent and rapidly
      reversible. These data are consistent with a reversible competitive inhibition of
      COX-1. 5. DFU inhibited lipopolysaccharide (LPS)-induced PGE2 production (COX-2)
      in a human whole blood assay with a potency (IC50 = 0.28 +/- 0.04 microM) similar
      to indomethacin (IC50 = 0.68 +/- 0.17 microM). In contrast, DFU was at least 500
      times less potent (IC50 > 97 microM) than indomethacin at inhibiting coagulation
      induced TXB2 production (COX-1) (IC50 = 0.19 +/- 0.02 microM). 6. In a sensitive
      assay with U937 cell microsomes at a low arachidonic acid concentration (0.1
      microM), DFU inhibited COX-1 with an IC50 value of 13 +/- 2 microM as compared to
      20 +/- 1 nM for indomethacin. CGP 28238, etodolac and SC-58125 were about 10
      times more potent inhibitors of COX-1 than DFU. The order of potency of various
      inhibitors was diclofenac > indomethacin approximately naproxen > nimesulide
      approximately meloxicam approximately piroxicam > NS-398 approximately SC-57666 >
      SC-58125 > CGP 28238 approximately etodolac > L-745,337 > DFU. 7. DFU inhibited
      dose-dependently both the carrageenan-induced rat paw oedema (ED50 of 1.1 mg kg-1
      vs 2.0 mg kg-1 for indomethacin) and hyperalgesia (ED50 of 0.95 mg kg-1 vs 1.5 mg
      kg-1 for indomethacin). The compound was also effective at reversing LPS-induced
      pyrexia in rats (ED50 = 0.76 mg kg-1 vs 1.1 mg kg-1 for indomethacin). 8. In a
      sensitive model in which 51Cr faecal excretion was used to assess the integrity
      of the gastrointestinal tract in rats, no significant effect was detected after
      oral administration of DFU (100 mg kg-1, b.i.d.) for 5 days, whereas chromium
      leakage was observed with lower doses of diclofenac (3 mg kg-1), meloxicam (3 mg
      kg-1) or etodolac (10-30 mg kg-1). A 5 day administration of DFU in squirrel
      monkeys (100 mg kg-1) did not affect chromium leakage in contrast to diclofenac
      (1 mg kg-1) or naproxen (5 mg kg-1). 9. The results indicate that COX-1
      inhibitory effects can be detected for all selective COX-2 inhibitors tested by
      use of a sensitive assay at low substrate concentration. The novel inhibitor DFU
      shows the lowest inhibitory potency against COX-1, a consistent high selectivity
      of inhibition of COX-2 over COX-1 (>300 fold) with enzyme, whole cell and whole
      blood assays, with no detectable loss of integrity of the gastrointestinal tract
      at doses >200 fold higher than efficacious doses in models of inflammation,
      pyresis and hyperalgesia. These results provide further evidence that prostanoids
      derived from COX-1 activity are not important in acute inflammatory responses and
      that a high therapeutic index of anti-inflammatory effect to gastropathy can be
      achieved with a selective COX-2 inhibitor.

PMID- 9146895
TI  - Trophic effect of angiotensin II in neonatal rat cardiomyocytes: role of
      endothelin-1 and non-myocyte cells.
AB  - 1. Angiotensin II (AII) and the endothelins (ET) are known to be potent trophic
      stimuli in various cells including cardiomyocytes. In order to characterize
      further these effects we studied, in neonatal rat ventricular cardiomyocytes, the
      effects of several endothelin-receptor antagonists and the AT1-receptor
      antagonist losartan on AII- and endothelin-induced inositol phosphate (IP)
      formation (assessed as accumulation of total [3H]-IPs in myo-[3H]-inositol
      prelabelled cells) and increase in rate of protein synthesis (assessed as [3H]
      phenylalanine incorporation). 2. Endothelin (10 pM-1 microM) concentration
      dependently increased IP-formation (max. increase at 100 nM ET-1: 130 +/- 14%
      above basal, n = 25) and [3H]-phenylalanine incorporation (max. increase at 1
      microM: 52 +/- 4% above basal, n = 16) with an order of potency: ET-1 > > ET-3.
      Both effects were antagonized by the ETA/ETB-receptor antagonist bosentan and the
      ETA-receptor antagonist BQ-123, but not affected by the ETB-receptor antagonist
      IRL 1038 and the AT1-receptor antagonist losartan. 3. Pretreatment of the cells
      with 500 ng ml-1 pertussis toxin (PTX) overnight that completely inactivated PTX
      sensitive G-proteins did not attenuate but rather enhance ET-1-induced IP
      formation. On the other hand, in PTX-pretreated cardiomyocytes ET-1-induced [3H]
      phenylalanine incorporation was decreased by 39 +/- 5% (n = 5). 4. All (1 nM-1
      microM) concentration-dependently increased IP-formation (max. increase at 1
      microM: 42 +/- 7% above basal, n = 16) and [3H]-phenylalanine incorporation (max.
      increase at 1 microM: 29 +/- 2%, n = 9). These effects were antagonized by
      losartan, but they were also antagonized by bosentan and BQ-123. 5. In well
      defined cultures of cardiomyocytes (not contaminated with non-myocyte cells) All
      failed to increase [3H]-phenylalanine incorporation: addition of non-myocyte
      cells to the cardiomyocytes restored All-induced increase in [3H]-phenylalanine
      incorporation. 6. We conclude that, in rat neonatal ventricular cardiomyocytes,
      (a) the ET-1-induced increase in rate of protein synthesis (through ETA-receptor
      stimulation) involves at least two signalling pathways: one via a PTX-insensitive
      G-protein coupled to IP-formation, and the other one via a PTX-sensitive G
      protein, and (b) the trophic effects of All are brought about via local ET-1
      secretion upon AT1-receptor stimulation in neonatal rat ventricular non-myocyte
      cells.

PMID- 9146897
TI  - Down-regulation of aortic and cardiac AT1 receptor gene expression in transgenic
      (mRen-2) 27 rats.
AB  - 1. Transgenic(TG) (mRen-2) rats overexpressing the mouse renin gene develop
      fulminant hypertension and cardiac hypertrophy. Since the activation of AT1
      receptor by angiotensin II is involved in blood pressure regulation, cardiac
      performance and myocardial growth, we investigated the biological effects of
      angiotensin II and the regulation of the AT1 receptor in the heart and aorta of
      TGR (mRen-2)27 rats in comparison to control animals. 2. Contraction studies on
      isolated cardiac muscle strips reveal that angiotensin II exerts no positive
      inotropic effect on the left ventricular myocardium of both, transgenic and
      control rats. In contrast, angiotensin II leads via AT1 receptor activation in
      the left atrium of control rats to a significant contraction (130 +/- 5% of basal
      contraction) which is not detectable in left atrium preparations of the
      transgenic animals. Furthermore, AT1 receptor activation causes a profound
      contraction of aortic rings isolated from control rats amounting to 1.39 +/- 0.2
      mN mg-1 wet weight, whereas aortic rings from TGR (mRen-2)27 rats contract only
      minimally upon angiotensin II stimulation (0.2 +/- 0.02 mN mg-1 wet weight). 3.
      These altered physiological responses of angiotensin II in the transgenic rats
      are in part due to a marked down-regulation of the AT1 receptor in atrial,
      ventricular and aortic tissue of these transgenic animals in comparison to
      control Sprague-Dawley rats, as shown by radioligand binding assays and
      quantitative polymerase chain reaction (PCR) experiments. The AT1 receptor
      density Bmax in the left atrium was 1.3 +/- 0.08 fmol mg-1 protein in control
      rats (KD 1.1 +/- 0.18 nmol l-1) and 0.94 +/- 0.15 fmol mg-1 protein (KD 2.1 +/-
      0.3 nmol l-1. In the aorta Bmax values were 15.1 +/- 0.5 fmol mg-1 protein (KD
      1.9 +/- 0.27 nmol l-1) for control rats and 11.3 +/- 0.76 fmol mg-1 protein (KD
      1.9 +/- 0.27 nmol l-1) for the TGR(mRen-2)27 rats AT1 receptor mRNA was reduced
      in the transgenic animals to 46 +/- 3% in the left atrium, 50 +/- 11% in the left
      ventricle and 40 +/- 3% in the aorta, respectively. 4. Together, the AT1 receptor
      is down-regulated in TGR (mRen-2)27 rats in comparison to wildtype Sprague Dawley
      rats leading to a profoundly decreased response of cardiac and aortic tissue upon
      stimulation with angiotensin II.

PMID- 9146896
TI  - Characterization of the induction of nitric oxide synthase and cyclo-oxygenase in
      rat aorta in organ culture.
AB  - 1. Within vessels, the formation of nitric oxide (NO) or prostaglandins is
      normally catalysed in the endothelium by constitutive isoforms of NO synthase
      (eNOS) and cyclo-oxygenase (COX-1), respectively. However, during inflammatory
      conditions, the underlying smooth muscle acquires the ability to release NO and
      prostaglandins after the expression of inducible isoforms of NOS (iNOS) and COX
      (COX-2). The co-induction of iNOS and COX-2 has been studied over 24 h in
      isolated vascular smooth muscle cells in vitro. However, due to the limitation of
      using cultured cells, the relationship between the activities of iNOS and COX
      over longer periods has not been addressed. Moreover, the relative contribution
      of the endothelium to the production of NO and prostaglandins under inflammatory
      conditions is not completely understood. 2. Here using an organ culture system,
      we have determined the profile of COX (6-keto prostaglandin F1 alpha (6-keto PGF1
      alpha), PGE2, thromboxane B2 (TXB2) and NOS (nitrite and nitrate) metabolites
      released over a period of 10 days from segments of rat aorta. In each case,
      segments from the same animal were left untreated or treated with bacterial
      lipopolysaccharide (LPS; 10 micrograms ml-1) in order to induce iNOS and COX-2.
      Prostaglandins were measured by radioimmunoassay whilst nitrite and nitrate were
      measured, respectively, by Greiss reaction alone, or following a nitrate
      reductase step. The isoforms of NOS and COX responsible for metabolite release
      were characterized pharmacologically by use of inhibitors and at the molecular
      level by reverse transcription polymerase chain reaction with specific primers
      for iNOS, eNOS, COX-1 and COX-2. In separate experiments the role of the
      endothelium in the release of nitrite, nitrate and prostaglandins and in the
      expression of iNOS, eNOS, COX-1 and COX-2 was determined by comparing responses
      in endothelium denuded and endothelium-intact segments of rat aorta. 3. Under
      control culture conditions vessels released prostaglandins in the following rank
      order 6-keto PGF1 alpha = PGE2 > > TXB2. LPS increased the release of 6-keto PGF1
      alpha and PGE2 but not of TXB2, an effect that was inhibited by the protein
      synthesis inhibitor cycloheximide (1 microM), the anti-inflammatory steroid
      dexamethason (1 microM), the nonsteroidal anti-inflammatory drug indomethacin (30
      microM) and, where tested, the selective COX-2 inhibitor NS-398 (30 microM).
      Similarly, segments of rat aorta released detectable levels of nitrite and
      nitrate, which were reduced by NG-nitro-L-arginine methyl ester (L-NAME, 1 mM),
      which inhibits all isoforms of NOS, and by dexamethasone (1 microM), which
      inhibits the induction of iNOS. The proportion of nitrate to nitrite released
      over the 10 day period varied greatly from approximately 1:1 on days 5 to 8 to
      5:1 on day 9. However, the sum of nitrite and nitrate (NOx) as well as PGE2
      remained elevated over the whole 10 day period. The formation of 6-keto PGF1
      alpha peaked on days 1 and 2. 4. In freshly prepared tissue, mRNAs for eNOS, COX
      1, iNOS and COX-2 were detected. After 24 h in culture, there was an apparent
      increase in the level of mRNAs for iNOS and COX-2 but not for eNOS or COX-1, an
      effect that was further enhanced when LPS was included in the culture medium. The
      expressions of mRNA for eNOS, COX-1, iNOS or COX-2 were not greatly different in
      vessels with intact or disrupted endothelium. Similarly the release of NOx or
      PGE2 by vessels after the 1st or 9th day in culture were not significantly
      different from vessels prepared with or without endothelium. 5. Thus, COX-2 and
      iNOS are co-induced in intact vessels in culture, with the vascular smooth muscle
      being the main site of mediator generation. In contrast to data from isolated
      cells in culture (observed usually over 1 day), both COX and NOS activities in
      cultured blood vessels were elevated for at least 10 days. Also, unlike isolated
      cells in culture, the COX and NOS pathways were active independently; L-NAME had
      little effect on the activity of COX and indomethacin had little effect on the
      activity of NOS.

PMID- 9146898
TI  - Involvement of voltage-dependent potassium channels in the EDHF-mediated
      relaxation of rat hepatic artery.
AB  - 1. In the rat hepatic artery, the acetylcholine-induced relaxation mediated by
      endothelium-derived hyperpolarizing factor (EDHF) is abolished by a combination
      of apamin and charybdotoxin, inhibitors of small (SKCa) and large (BKCa)
      conductance calcium-sensitive potassium (K)-channels, respectively, but not by
      each toxin alone. The selective BKCa inhibitor iberiotoxin cannot replace
      charybdotoxin in this combination. Since delayed rectifier K-channels (KV)
      represent another target for charybdotoxin, we explored the possible involvement
      of KV in EDHF-mediated relaxation in this artery. 2. The KV inhibitors, agitoxin
      2 (0.3 microM), kaliotoxin (0.3 microM), beta-dendrotoxin (0.3 microM),
      dofetilide (1 microM) and terikalant (10 microM), each in combination with apamin
      (0.3 microM) had no effect on the EDHF-mediated relaxation induced by
      acetylcholine in the presence of N omega-nitro-L-arginine (0.3 mM) and
      indomethacin (10 microM), inhibitors of nitric oxide (NO) synthase and cyclo
      oxygenase, respectively (n = 2-3). Although the KV inhibitor margatoxin (0.3
      microM) was also without effect (n = 5), the combination of margatoxin and apamin
      produced a small inhibition of the response (pEC50 and Emax values were 7.5 +/-
      0.0 and 95 +/- 1% in the absence and 7.0 +/- 0.1 and 81 +/- 6% in the presence of
      margatoxin plus apamin, respectively; n = 6; P < 0.05). 3. Ciclazindol (10
      microM) partially inhibited the EDHF-mediated relaxation by shifting the
      acetylcholine-concentration-response curve 12 fold to the right (n = 6; P < 0.05)
      and abolished the response when combined with apamin (0.3 microM; n = 6). This
      combination did not inhibit acetylcholine-induced relaxations mediated by
      endothelium-derived NO (n = 5). 4. A 4-aminopyridine-sensitive delayed rectifier
      current (IK(V)) was identified in freshly-isolated single smooth muscle cells
      from rat hepatic artery. None of the cells displayed a rapidly-activating and 
      inactivating A-type current. Neither charybdotoxin (0.3 microM; n = 3) nor
      ciclazindol (10 microM; n = 5), alone or in combination with apamin (0.3 microM;
      n = 4-5), had an effect on IK(V). A tenfold higher concentration of ciclazindol
      (0.1 mM, n = 4) markedly inhibited IK(V), but this effect was not increased in
      the additional presence of apamin (0.3 microM; n = 2). 5. By use of membranes
      prepared from rat brain cortex. [125I]-charybdotoxin binding was consistent with
      an interaction at a single site with a KD of approximately 25 pM. [125I]
      charybdotoxin binding was unaffected by iberiotoxin (0.1 microM, n = 6), but was
      increased by apamin in a concentration-dependent manner (Emax 43 +/- 10%, P <
      0.05 and pEC50 7.1 +/- 0.2; n = 7-8). Agitoxin-2 (10 nM) displaced [125I]
      charybdotoxin binding by 91 +/- 3% (n = 6) and prevented the effect of apamin (1
      microM; n = 6). 6. It is concluded that the EDHF-mediated relaxation in the rat
      hepatic artery is not mediated by the opening of either KV or BKCa. Instead, the
      target K-channels for EDHF seem to be structurally related to both KV and BKCa.
      The possibility that a subtype of SKCa may be the target for EDHF is discussed.

PMID- 9146899
TI  - Purine and pyrimidine nucleotide receptors in the apical membranes of equine
      cultured epithelia.
AB  - 1. The short circuit current (ISC) technique was used to quantify electrolyte
      transport by equine cultured sweat gland epithelia. Adenosine 5'-triphosphate
      (ATP) and certain related compounds, caused transient increases in ISC when added
      to the apical solution. The order of potency was uridine triphosphate (UTP) > ATP
      > ADP > > AMP = adenosine. 2. The responses to apical nucleotides were due to
      chloride and bicarbonate secretion and were reduced in pertussis toxin-treated
      cells. P2-receptors sensitive to uridine 5'-triphosphate (UTP), that interact
      with inhibitory G proteins, therefore appear to be present in the apical
      membrane. 3. Responses to ATP and UTP were reduced in cells loaded with BAPTA, a
      calcium chelator. BAPTA attenuated the response to ATP more than the response to
      UTP suggesting that these nucleotides may not act via a common pathway. 4. Cross
      desensitization experiments indicated that two populations of UTP-sensitive
      receptor were present. One was sensitive to UTP and ATP, whereas the second was
      sensitive only to UTP. Uridine diphosphate appeared to activate the ATP
      insensitive receptor population selectively. 5. These data suggest that apical
      pyrimidinoceptors may be expressed by these cells. The physiological role of
      these receptors is unknown but they may allow the autocrine regulation of
      epithelial function.

PMID- 9146900
TI  - Ontogeny of the solitary chemosensory cells in the zebrafish, Danio rerio.
AB  - Secondary epidermal solitary chemosensory cells (SCCs) are widespread among the
      primary aquatic vertebrates. They resemble taste bud sensory cells in fine
      structure and may be innervated from facial or spinal nerves. According to
      previous studies, SCCs may constitute a water sampling system in the contexts of
      predator avoidance, habitat recognition and, in some cases, finding food. By
      quantitative scanning (SEM) and transmission electron microscopy (TEM) in 60
      specimens (57 SEM, 3 TEM) of 16 developmental stages, from pre-hatchlings to
      adults, we describe the ontogenetic development of SCC densities and shapes of
      sensory apices in the zebrafish, Danio rerio. This is put into perspective with
      the ontogeny of external taste buds. Just prior to hatching, 3 days after
      fertilization (3d AF), sensory apices of SCCs penetrate between the squamous
      epidermal cells, whereas taste bud pores only appear at the onset of exogenous
      feeding (5d AF). SCC densities increase sharply from hatching shortly after
      metamorphosis (25d AF) up to 6 x 10(3) per mm2 on the head and remain relatively
      constant in density thereafter. Conservatively estimated, there may be
      approximately 3.2 x 10(5) SCCs on the head and 1 x 10(6) SCCs on the entire body
      surfaces of a zebrafish 180d AF. SCCs are spread evenly, but are 2- to 5-fold
      higher in density along the head than along the body. Sensory apices are brush
      like in hatchlings and early juveniles, but tend to consist of a single villus in
      the adults. This ontogenetic change of SCC apices parallels the evolutionary
      change from 'oligovillous' cells in lampreys and elasmobranchs to the
      'monovillous' SCCs in the advanced actinopterygian teleosts.

PMID- 9146901
TI  - Analysis of medication off-odors using an electronic nose.
AB  - Packaging materials have been implicated as a source for off-odors in
      pharmaceutical products. A new instrumentation method employing an array of
      conducting polymer gas sensors was used to identify the offending packaging
      components in the canister of a pharmaceutical inhalant. A case study is
      described in which tainted inhalers as well as elastomeric components of the
      canisters were 'sniffed' by the electronic nose. The electronic nose was able to
      differentiate between tainted and untainted canisters. Signal processing
      algorithms performed on the raw data from the sensors suggested that specific
      elastomeric components were responsible for the off-odor. A further experiment
      suggested that the propellant (Freon) extracted the odor from the elastomeric
      components as the medication was expelled from the canister. These data indicate
      that the electronic nose is a potential tool to solve odor problems in which
      human odor assessment is not feasible due to excess exposure to the medically
      active ingredient.

PMID- 9146902
TI  - Response of pigs to bitter-tasting compounds.
AB  - Two-bottle preference tests were done to determine whether pigs detect bitter
      tasting compounds. Four standard bitter compounds and nine bitter-tasting
      pharmaceutical compounds were tested. Pigs detect and avoid taste compounds that
      humans perceive as bitter-tasting. A dose-response to varying concentrations of
      bitter tastants can be measured.

PMID- 9146903
TI  - Different characteristics of gustatory responses between the greater superficial
      petrosal and chorda tympani nerves in the rat.
AB  - The integrated responses to gustatory stimuli applied to the soft palate were
      recorded from the greater superficial petrosal nerve (GSP) and were compared with
      those from the chorda tympani nerve (CT) innervating the anterior part of the
      tongue in the rat. Stimuli included various concentrations of NaCl, sucrose, HCl
      and quinine hydrochloride, and 0.5 M of six sugars. The inhibitory effects of
      amiloride on the responses to sodium salts, including various concentration of
      NaCl, 0.1 M sodium acetate and 0.01 M sodium saccharin, were also tested. Both
      the phasic and tonic responses to sugars in the GSP were significantly larger
      than those in the CT, whereas both responses to NaCl in the GSP were
      significantly smaller than those in the CT. Although amiloride at 50 microM
      significantly depressed the phasic and tonic responses to NaCl with a wide range
      of concentration in the CT, little inhibitory effect was observed in the GSP. The
      tonic response to sodium acetate, when dissolved in amiloride solution, was
      depressed to 15% of the control in the CT, and slightly but significantly
      depressed to 70% in the GSP. These response characteristics of the GSP may play
      important roles in the processing of gustatory information.

PMID- 9146904
TI  - Mineralocorticoid (type I) receptors in the olfactory mucosa of the mammal:
      studies with [3H]aldosterone and the anti-mineralocorticoid spironolactone.
AB  - High-affinity, specific binding sites to mineralocorticoids, with characteristics
      of mineralocorticoid (type I) receptors, have been found in the mammalian
      olfactory mucosa. In the presence of RU 28362, which blocks low-affinity binding
      of the labeled hormone to glucocorticoid (type II) receptors, Scatchard analysis
      of the specific [3H]aldosterone binding indicates that aldosterone binds to a
      single class of high-affinity (type I) sites with a dissociation constant, Kd, of
      1.2 x 10(-9) M and a maximum number of binding sites, Bmax, of 63 fmol/mg dry
      tissue. Time course of association of [3H]aldosterone and its binding sites
      showed maximal binding by 30 min at 25 degrees C which remained unchanged up to
      90 min. Competition studies performed with 1 x 10(-7)-1 x 10(-5) M
      spironolactone, a competitive mineralocorticoid antagonist, showed a dose
      response reduction of [3H]aldosterone binding, implying that in the olfactory
      mucosa this compound behaves as an aldosterone antagonist. These results
      demonstrate significant [3H]aldosterone binding to receptors of high affinity and
      mineralocorticoid specificity and suggest that the olfactory mucosa is a target
      site for mineralocorticoid action.

PMID- 9146905
TI  - The hydrostatic and hydrodynamic volumes of polyols in aqueous solutions and
      their sweet taste.
AB  - The tastes and solution properties of sugar alcohols were studied in an attempt
      to illuminate the mechanism of sweet taste chemoreception. The SMURF method was
      used to measure tastetime-intensity of aqueous solutions of sugar alcohols and
      the results were interpreted using the Stevens power function and kinetic
      parameters. The apparent molar volumes, apparent specific volumes, partial molar
      volumes, partial specific volumes and intrinsic viscosities of the solutions were
      studied. Apparent molar volume reflects the size of the molecule in a hydrostatic
      state whereas intrinsic viscosity gives a measure of the size of the molecules in
      a hydrodynamic state. Generally the apparent molar volumes of the polyols are 6
      13% greater than those of the parent sugars, indicating less interaction with the
      water structure. Apparent specific volume values can predict taste quality, and
      the average apparent specific volume for the sugar alcohols studied fits within
      the central part of the sweet range, i.e. 0.5-0.68 cm3/g, which accords with
      their ability to elicit a pure sweet taste response. Intensities and persistences
      of sweetness in the polyols followed the same trend as intrinsic viscosities.

PMID- 9146906
TI  - Changes in outward K+ currents in response to two types of sweeteners in sweet
      taste transduction of gerbil taste cells.
AB  - Using the whole cell patch clamp technique, we measured changes in outward K+
      currents of gerbil taste cells in response to different kinds of sweeteners.
      Outward K+ currents of the taste cell induced by depolarizing pulses were
      suppressed by sweet stimuli such as 10 mM Na-saccharin. The membrane-permeable
      analog of cAMP, cpt-cAMP, also decreased outward K+ currents. On the other hand,
      the K+ currents were enhanced by amino acid sweeteners such as 10 mM D
      tryptophan. The outward K+ current was enhanced by external application of Ca(2+)
      transporting ionophore, 5 microM ionomycin, and intracellular application of 5
      microM inositol-1,4,5-trisphosphate (IP3). The outward K+ currents were no longer
      suppressed by 10 mM Na-saccharin containing 20 microM gurmarin, but were still
      enhanced by 10 mM D-tryptophan containing 20 microM gurmarin. These results
      suggest that sweet taste transduction for one group of sweeteners such as Na
      saccharin in gerbils is concerned with an increase of the intracellular cAMP
      level, and that the transduction for the other group of sweeteners such as D
      tryptophan is concerned with an increase of the intracellular IP3 level which
      releases Ca2+ from the internal stores.

PMID- 9146907
TI  - Influence of stimulus duration on a regional measure of NaCl taste sensitivity.
AB  - The present study demonstrates that perithreshold temporal integration occurs in
      the human taste system across stimulus durations ranging from 200 to 1500 ms in a
      manner analogous to that seen in other major sensory systems. Thus, the notion
      that gustation is comparatively insensitive to temporal stimulus parameters at
      threshold levels is disproved.

PMID- 9146908
TI  - Effect of nasal dilators on perceived odor intensity.
AB  - Subjects wearing nasal dilators rated olfactory stimuli as being more intense
      compared with ratings done without nasal expansion. The results support a
      perceptual constancy model in olfaction.

PMID- 9146909
TI  - Chromosome microdissection and microcloning.

PMID- 9146910
TI  - Rapid detection of euchromatin by Alu-PRINS: use in clinical cytogenetics.
AB  - Alu-PRINS was successful in providing positive identification of euchromatin when
      oligoprimers were used at either extremity of the consensus Alu sequence. This
      technique was sensitive, as shown by the ability to detect small regions of
      euchromatin translocated to the short arm of an acrocentric chromosome. Since the
      Alu-PRINS technique is rapid and relatively simple, it will be useful in the
      diagnostic cytogenetics laboratory for the assessment of aberrant short arms of
      acrocentric satellites. This technique was also useful in defining the structure
      of small accessory marker chromosomes.

PMID- 9146911
TI  - Comparative analysis on the distribution of heterochromatin in Citrus, Poncirus
      and Fortunella chromosomes.
AB  - Double fluorochrome staining with chromomycin A3 (CMA) and 4'-6-diamidino-2
      phenylindole (DAPI) was used to characterize and compare the distribution of
      constitutive heterochromatin along chromosomes of Citrus, Poncirus and Fortunella
      species. Only CMA-positive bands were distinguishable in metaphase chromosomes.
      Preferential distribution of heterochromatin in terminal regions, mainly of the
      long arm, and centromeric regions of a few long chromosomes was a common feature
      of these genera. Heteromorphism between possible homologous chromosomes was
      present in the majority of species. Citrus and Poncirus revealed some remarkably
      uniform chromosomes without any intensively fluorescing region, whereas
      Fortunella cultivars were differentiated by the presence of CMA bands in all
      chromosomes. Through measurements assisted by a computer, amounts of CMA-positive
      regions were shown to be highest in Fortunella. Similarities between Citrus and
      Poncirus suggest little heterochromatin diversification among karyotypes of these
      genera, whereas Fortunella, with higher amounts and more homogenous distribution
      of heterochromatin, is more divergent.

PMID- 9146912
TI  - Molecular characterization and cytological mapping of a non-repetitive DNA
      sequence region from the W chromosome of chicken and its use as a universal probe
      for sexing carinatae birds.
AB  - A non-repetitive genomic DNA region of about 25 kb was cloned from the W
      chromosome of chicken using a genomic library prepared from a single W chromosome
      of the chicken. This region was mapped by fluorescence in situ hybridization
      (FISH) with mitotic and lampbrush chromosomes to a position between the major
      EcoRI family and the pericentromeric Xhol family on the W chromosome. A 0.6-kb
      EcoRI fragment (EE0.6) subcloned from this region consists of a sequence that can
      be obtained by the exon-trapping procedure and flanking sequences. Sequences,
      which are closely similar to that of EE0.6, are widely conserved on the W
      chromosomes of Carinatae birds, as revealed by Southern blot hybridization to
      HindIII-digested female and male genomic DNAs from 18 species of birds belonging
      to eight different taxonomic orders. The female sex of those birds can be
      determined by the presence of an unambiguous female-specific band. For many
      species of birds, the female sex can also be determined by polymerase chain
      reaction (PCR) using a set of primers from the flanking sequences in the chicken
      EE0.6.

PMID- 9146913
TI  - Isolation of chromosome-specific paints from high-resolution flow karyotypes of
      the sheep (Ovis aries).
AB  - High-resolution bivariate flow karyotypes were obtained using fibroblast cell
      lines from a sheep with a normal karyotype (2n = 54), from sheep carrying
      Robertsonian translocation chromosomes and from sheep-hamster somatic cell
      hybrids. By taking advantage of the presence of chromosome polymorphisms,
      translocation chromosomes and sheep-hamster somatic cell hybrids, all sheep
      chromosomes were isolated by flow sorting. Chromosome-specific paints were
      generated from each sorted peak using degenerate oligonucleotide-primed
      polymerase chain reaction (DOP-PCR). The sheep chromosome present in each peak
      was identified by chromosome-specific microsatellite analysis of the DOP-PCR
      products and fluorescence in situ hybridization (FISH) onto DAPI-banded sheep
      metaphase chromosomes. The chromosome-specific DNA obtained in this study can be
      used for the production of genomic libraries and as a resource for mapping
      randomly cloned DNA sequences that will greatly aid the construction of genetic
      and physical maps in the sheep. The chromosome-specific paints will facilitate
      chromosome identification and contribute to the study of karyotype evolution in
      the sheep and related species.

PMID- 9146914
TI  - A reappraisal of the tandem fusion theory of karyotype evolution in Indian
      muntjac using chromosome painting.
AB  - We have tested the tandem fusion hypothesis of the origin of the Indian muntjac
      karyotype (2n = 6/7) by using reciprocal chromosome painting between the Indian
      muntjac, Chinese muntjac (n = 46) and brown brocket deer (2n = 70 + 3B) with
      chromosome-specific paint probes derived from flow-sorted chromosomes of these
      three deer species. Our results have shown that the euchromatic blocks of all
      chromosome arms of the brown brocket deer have been conserved apparently
      unchanged in number and content in the Indian muntjac. While confirming the
      conservation in toto of most of Chinese muntjac euchromatin in the karyotype of
      the Indian muntjac, we demonstrate that the synteny of chromosomes 1, 2, 3, 4 and
      5 of the Chinese muntjac has been disrupted by chromosome rearrangements other
      than fusions. This indicates that the present karyotype of the Indian muntjac
      cannot be reconstructed from the hypothetical Chinese muntjac-like 2n = 46
      ancestral karyotype exclusively by chromosome fusions. Furthermore, we have shown
      that the breakpoints of these rearrangements appear to have occurred near to the
      fusion points formed during the origin of the 2n = 46 karyotype of the Chinese
      muntjac from a 2n = 70 karyotype, which is believed to be ancestral for the
      family Cervidae. Moreover, we substantiate that on the Indian muntjac
      chromosomes, the C5 probe, which is derived from the centromeric satellite
      sequences of the Chinese muntjac, maps to the putative fusion points determined
      by comparative chromosome painting and presumably represents the remnants of
      ancestral centromeric sequences.

PMID- 9146915
TI  - Analysis of chromosome 6 deletions in lymphoid malignancies provides evidence for
      a region of minimal deletion within a 2-megabase segment of 6q21.
AB  - Fluorescence in situ hybridization has been used to define deletion breakpoints
      within chromosome bands 6q16-21 in cases of lymphoid malignancy. Previous
      evidence suggested that the region might contain a tumour-suppressor gene. Six
      yeast artificial chromosome probes, each selected using a single marker, were
      localized to 6q16-21 and the following order was confirmed; D6S330-D6S283-D6S301
      D6S447-D6S246-FYN+ ++. Of 32 cases of lymphoid malignancy, 30 showed deletion of
      D6S246 and, in the two cases in which D6S246 was retained, the adjacent marker,
      D6S447, was deleted. These observations imply that a region of minimal deletion
      is located within a 2-megabase segment of 6q21, between D6S447 and D6S246,
      providing a candidate region for the location of a tumour-suppressor gene.

PMID- 9146916
TI  - Nucleolar dominance in triticales: control by unlinked genes.
AB  - Hybrid plants and animals often show suppression of activity of ribosomal genes
      (rDNA) originating from one of the parental or ancestral species. In the wheat x
      rye amphiploid triticale, containing 28 chromosomes of wheat origin and 14 from
      rye, rDNA of rye origin (on chromosome 1R) is not normally expressed, while the
      1B- and 6B-origin rDNA from wheat shows strong expression. Expression of rDNA can
      be accurately assessed by the silver staining method, which stains both
      interphase nucleoli and metaphase rDNA sites that were actively expressed at the
      previous interphase. We show here that substitution of another rye chromosome,
      2R, by a chromosome from hexaploid wheat, 2D (triticale-2D(2R)), prevents
      suppression of the rye-origin rDNA, and leads to activity of all six major rDNA
      loci. These results were found in two different triticales and supported by rDNA
      behaviour in wheat-rye chromosomal addition lines. Models for chromosomal
      interactions leading to control of rDNA expression are presented.

PMID- 9146917
TI  - Characterization of internal DNA-binding and C-terminal dimerization domains of
      human centromere/kinetochore autoantigen CENP-C in vitro: role of DNA-binding and
      self-associating activities in kinetochore organization.
AB  - Human centromere protein C (CENP-C), a chromosomal component of the inner plate
      of kinetochores, was originally identified as one of the centromere autoantigens.
      In a previous study, we showed that it possesses DNA-binding activity in vitro.
      Recently, centromere-binding activity was suggested at the C-terminal region in
      vivo. However, little is known about the role of CENP-C in kinetochore
      organization. Here, to characterize its biochemical properties, three separate
      antigenic regions of human CENP-C were expressed in Escherichia coli, affinity
      purified and used in South-western blotting and chemical cross-linking analyses.
      We found that the internal DNA-binding domain was composed of two kinds of
      elements: the 'core' and two flanking 'stabilizing' elements that support the
      activity. When cross-linked with disuccinimidyl suberate (DSS), the N-terminal
      region produced the ladder bands of dimer and tetramer: the C-terminal region
      exclusively produced the dimer band, whereas the internal region was not affected
      at all. Dimer formation at the C-terminus in the native state was also indicated
      by gel filtration and the presence of conformation-specific autoantibodies in the
      patient's sera. These results suggest that human CENP-C consists of three
      functional units required for 'kinetochore assembly': a putative N-terminal
      oligomerization domain, an internal DNA-binding domain and a C-terminal
      dimerization domain.

PMID- 9146918
TI  - A study of silver-stained nucleolus organizer regions in metaphase chromosomes of
      cambial cells of mouse and rat placenta.

PMID- 9146920
TI  - An accelerated in situ hybridization procedure using microwave irradiation.

PMID- 9146919
TI  - A fast, novel approach for DNA fibre-fluorescence in situ hybridization analysis.

PMID- 9146921
TI  - Mevalonate kinase map position 12q24.

PMID- 9146922
TI  - The third human isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
      (PFKFB3) map position 10p14-p15.

PMID- 9146923
TI  - Cyclophilin 40 (PPID) gene map position 4q31.3.

PMID- 9146924
TI  - Nitric oxide: initiator and modulator.

PMID- 9146925
TI  - Airway remodelling takes place in asthma--what are the clinical implications?

PMID- 9146926
TI  - Dog allergy: understanding our 'best friend'?

PMID- 9146927
TI  - Nasal nitric oxide is increased in allergic rhinitis.
AB  - BACKGROUND: Nitric oxide (NO) plays a major role in the regulation of vascular
      tone and in non-specific host defence. The epithelium in the paranasal sinuses
      was recently identified as the major site of NO production in the upper airways.
      OBJECTIVE: To investigate NO status in allergic rhinitis, we compared the NO
      concentration in the nasal cavities of control subjects (n = 19) and in patients
      with allergic rhinitis (n = 36) with symptoms (WS, n = 17) or without symptoms
      (WOS, n = 19) on the day of the test. METHODS: NO concentration was measured
      using a chemiluminescent analyser aspiring from each nasal cavity at a sampling
      flow rate of 0.7 L/min, before and 10 min after administration of a nasal
      vasoconstrictor. RESULTS: The mean NO concentration (+/- SE) in the control was
      235 +/- 11 ppb and 225 +/- 9 ppb in the right and left nostrils respectively, and
      was decreased by 14% and 12% by the nasal vasoconstrictor (P < 0.001). The NO
      concentration in patients with allergic rhinitis was significantly higher in the
      right and left nostrils (382 +/- 20 ppb and 396 +/- 28 respectively, P < 0.0001
      versus control). All WOS patients demonstrated normal or increased NO
      concentrations in both nostrils, whereas two WS patients showed decreased NO
      concentrations in the left nostril. Inhalation of a nasal vasoconstrictor
      increased NO concentration by 6% and 27% in the right and left nostrils
      respectively in WS patients. CONCLUSION: Nasal NO concentration is increased in
      patients with allergic rhinitis. Interestingly, patients without symptoms on the
      day of the test also showed a clear-cut increase in nasal NO production, which
      could reflect a permanent inflammation of the sinus mucosa.

PMID- 9146928
TI  - The measurement of reticular basement membrane and submucosal collagen in the
      asthmatic airway.
AB  - BACKGROUND: An increase in types III and V collagen below the bronchial
      epithelium of the airway is known to be responsible for apparent thickening of
      the reticular basement membrane (RBM) and is recognized as a characteristic
      feature of asthma. Wide variations exist in reported ranges of the thickness of
      the RBM in both asthmatic and control airways. The description of collagen
      deposition has been confined to the RBM with no previous reports of increased
      collagen deeper within the bronchial wall (i.e. submucosa), although inflammation
      is known to extend to deeper levels. OBJECTIVE: The objective of this study was
      to compare different methods used to measure RBM thickness and to examine
      collagen deposition in deeper asthmatic bronchial submucosa. METHODS: We examined
      bronchial mucosal biopsies from 15 asthmatic and 13 normal healthy controls to
      measure RBM thickness by light and electron microscopic methods on resin sections
      and to estimate the extent of collagen deposition in the submucosa by
      immunochemical staining with monoclonal antibodies to collagen subtypes on
      paraffin sections. RESULTS: Simple staining with toluidine blue on resin sections
      coupled with light microscopic evaluation was as accurate and less expensive than
      electron microscopic methods in the measurement of the thickness of RBM (mean +/-
      SD, light microscopy: asthma vs control, 6.01 +/- 2.09 vs 3.19 +/- 0.55 microns,
      P < 0.001; electron microscopy: asthma vs control, 6.09 +/- 2.19 vs 2.85 +/- 0.86
      microns, P < 0.01). Using monoclonal antibodies to collagen subtypes and image
      analysis methods, we identified increased collagen in the submucosa in asthma
      (type III collagen, asthma vs control: 62 +/- 7 vs 51 +/- 9%, P < 0.05, type V
      collagen, asthma vs control: 60 +/- 6 vs 52 +/- 9%, P < 0.05). CONCLUSIONS: This
      study has demonstrated that the RBM may be reliably measured by light microscopic
      methods. This study shows for the first time that the submucosa of the asthmatic
      airway contains significantly more collagen than normal controls, giving rise to
      the possibility that airway scar formation may have greater functional
      implications than has been previously believed from consideration of the RBM
      alone.

PMID- 9146929
TI  - Elevated levels of substance P in tears of patients with allergic conjunctivitis
      and vernal keratoconjunctivitis.
AB  - BACKGROUND: Recent studies have suggested that the nervous system may participate
      in inflammatory processes. Substance P (SP) acts as a chemical mediator as well
      as a neurotransmitter. OBJECTIVE: In order to clarify the pathogenesis of ocular
      allergic diseases, we assessed the concentration of SP in tears. METHODS: Using a
      highly sensitive and specific double-antibody enzyme immunoassay (EIA), we
      determined the SP concentration in tears of 10 patients with seasonal allergic
      conjunctivitis, 10 with atopic dermatitis without keratoconjunctivitis (AD), 13
      with vernal keratoconjunctivitis (VKC) and 65 normal controls. Giemsa's staining
      for brush cytology samples and histocytological study by immunocytochemical
      staining of giant papillary conjunctival cells from VKC and normal controls was
      conducted. RESULTS: The mean SP level was low in the normal controls and AD,
      whereas patients with seasonal allergic conjunctivitis and VKC showed significant
      elevation of SP (P < 0.01). Brush cytology samples showed conjunctival epithelial
      cells with lymphocytes, neutrophils and eosinophils that were not seen in normal
      subjects. Histocytological examination demonstrated SP positive cells in the
      conjunctiva of patients with VKC, but not in normal controls. CONCLUSION: This
      study suggests that the increased level of SP in tears may contribute to the
      pathogenesis and severity of ocular allergic diseases.

PMID- 9146931
TI  - Altered compartmentalization of transforming growth factor-beta in asthmatic
      airways.
AB  - BACKGROUND: Asthma is characterized by alterations of the bronchial epithelium
      associated with inflammatory cell infiltrates and sub-epithelial fibrosis.
      Transforming Growth Factor-beta (TGF-beta) is an anti-inflammatory and fibrosing
      cytokine normally present in bronchial epithelial cells and also potentially
      produced by inflammatory cells. Thus, TGF-beta could play a role in the asthmatic
      process, and its expression could be modified in asthmatic airways. OBJECTIVE: To
      test this latter hypothesis, we studied the bronchial distribution of TGF-beta in
      asthmatic patients. METHODS: TGF-beta 1, 2, 3 distribution was studied by
      immunohistochemistry in bronchial biopsies from 12 asthmatic patients and 10 non
      asthmatic subjects. RESULTS: Bronchial epithelial cells from asthmatics were
      negative or faintly positive while a bright staining was detected in these from
      non-asthmatics (P < 0.01). In both groups, when inflammatory cells were present
      beneath the basement membrane, they were stained by the anti-TGF-beta antibody.
      CONCLUSION: This study shows an altered compartimentalization of TGF-beta in
      asthma. (a) TGF-beta is scarse in asthmatic bronchial epithelial cells, which
      could favour the perennization of the bronchial inflammation, and (b) TGF-beta is
      present in inflammatory cells beneath the basement membrane, where it could be
      involved in the frequent sub-epithelial fibrosis.

PMID- 9146930
TI  - Interleukin-8 secretion in patients with allergic rhinitis after an allergen
      challenge: interleukin-8 is not the main chemotactic factor present in nasal
      lavages.
AB  - BACKGROUND: Interleukin-8 (IL-8) is a chemotactic cytokine for neutrophils and
      primed eosinophils. In allergic rhinitis, allergen exposure triggers leucocyte
      recruitment. OBJECTIVE: We evaluated in this study IL-8 secretion and the
      neutrophil chemotactic activity in nasal lavages collected after a nasal allergen
      challenge. Moreover, the participation of IL-8 in the neutrophil chemotactic
      activity was quantified. METHODS: Four healthy subjects and 19 patients with
      allergic rhinitis were exposed to a nasal allergen challenge. As a control,
      saline challenge was performed in four patients with allergic rhinitis.
      Concentration of IL-8 was measured by ELISA in nasal lavages collected before and
      after challenge. Neutrophil chemotactic assay was developed using a 48-well
      chemotaxis microassembly. RESULTS: After allergen challenge, the healthy
      subjects, the four patients receiving saline and one patient exposed to allergen
      did not respond; seven patients presented a single early reaction and 11 patients
      a dual response. For healthy subjects and the four patients exposed to saline,
      the level of IL-8 did not increase after challenge in comparison with that at
      baseline. After allergen challenge, two peaks of IL-8 release were observed for
      patients with allergic rhinitis during the early (30 min to 1 h 30 min) and the
      late periods (3 h 30 min to 9 h 30 min), however the difference was not
      significant for the early period. During the late period, a significant increase
      in IL-8 concentrations was detected for the patients developing a dual response,
      whereas the difference was not significant for those presenting only an early
      reaction. The neutrophil chemotactic activity of nasal lavages from patients with
      allergic rhinitis collected during the early and the late reactions (17 +/- 2.1
      and 23.3 +/- 2.8 neutrophils per high power field (hpf), respectively) was
      significantly higher than the activity of lavage fluid collected at baseline (9.2
      +/- 1.8 neutrophils per hpf). Nevertheless, the addition of a neutralizing anti
      IL-8 antibody inhibited weakly the chemotactic activity of lavage fluid from
      rhinitic patients collected during the early or the late periods (18 and 11% of
      inhibition) (P = NS). CONCLUSION: These data show that allergen challenge
      increased significantly the secretion of IL-8 for the patients with allergic
      rhinitis. However, neutralization of IL-8 in nasal lavages by a specific antibody
      revealed that the role of this chemokine in granulocyte infiltrate was limited,
      suggesting that IL-8 acts in connection with other chemotactic factors in this
      recruitment.

PMID- 9146932
TI  - Identification of neutrophil chemotactic factors in bronchoalveolar lavage fluid
      of asthmatic patients.
AB  - BACKGROUND: Although neutrophils have been implicated in bronchial asthma, the
      mechanism(s) which bring these cells into the airways is poorly understood.
      OBJECTIVE: To investigate the presence and identity of neutrophil chemotactic
      factors in bronchoalveolar lavage (BAL) fluid from atopic asthmatic subjects.
      METHOD: BAL fluid was obtained from 13 subjects (seven asthmatics and six
      normals), aged 19 to 60 yr, at bronchoscopy. Separation of neutrophil chemotactic
      activity (NCA) was achieved by FPLC cation exchange chromatography. Fractions
      were collected and assayed for chemotaxis in multiwell micro-chemotaxes chambers
      using polycarbonate filters, for the complement peptide C5a/C5a des Arg by
      radioimmunoassay (RIA) and for interleukin-8 (IL-8) by ELISA. RESULTS: NCA was
      found in FPLC fractions of BAL samples in four out of seven asthmatics and each
      of these subjects had at least three similar peaks of NCA. The major peak of NCA
      was found to contain immunoreactive C5a/C5a des Arg and chemotaxis. In response
      to this NCA could be blocked by desensitization of the neutrophils with
      recombinant C5a. Purified serum derived C5a/C5a des Arg was found to have altered
      chromatographic properties when added to BAL fluid; this suggested that BAL fluid
      contained proteins which interacted with the C5a/C5a des Arg. Immunoreactive IL-8
      (iIL-8) was also detected but its concentration or chemical form was insufficient
      to induce neutrophil chemotaxis. CONCLUSION: This study demonstrates that
      bronchial asthmatic lavage fluid contains C5a/ C5a des/Arg and IL-8, together
      with other as yet unidentified factors which may contribute to neutrophil
      recruitment in this disease.

PMID- 9146933
TI  - Constitutive mRNA and immunoreactivity for IL-2 in human nasal mucosa.
AB  - BACKGROUND: The nasal mucosa is the initial site in the upper airway of host
      defence against antigenic challenge in the form of airborne allergens, irritants,
      toxins and infectious agents, and yet little is known about nasal mucosal
      cytokine expression and function. We hypothesized that IL-2 might play a role in
      immunocompetence of the upper airway. METHODS: IL-2 immunoreactivity was measured
      by ELISA in nasal secretions and by Western blot. Immunohistochemistry and
      electron microscopy were performed on turbinated tissue. mRNA for IL-2 was
      evaluated by RTPCR and Southern hybridization. RESULTS: IL-2 immunoreactivity was
      demonstrated by Western blot and quantitated by an enzyme immunoassay.
      Immunohistochemical and electron microscopy analysis of turbinate tissue revealed
      interstitial staining for IL-2. By RTPCR, IL-2 message was evident in 5/5 atopics
      and 5/5 non-atopics. IL-2 message was expressed in all subjects by Southern
      hybridization to an internal probe after PCR. CONCLUSION: This study has
      demonstrated constitutive expression of IL-2 protein and mRNA in the upper airway
      of healthy individuals. The further characterization of cytokines in the upper
      airway could provide useful insights into immune regulation at the mucosal level.

PMID- 9146934
TI  - Prevalence of latex sensitization in subjects attending health screening:
      implications for a perioperative screening.
AB  - BACKGROUND: Because latex is a common allergen, the rate of latex sensitization
      may be high in the general population. A major issue would then be to determine
      whether a systematic preoperative screening in the general population should be
      recommended. OBJECTIVE: The purpose of the study was to evaluate the prevalence
      of latex sensitization in a sample of the general population and to assess the
      role of possible risk factors. METHODS: The subjects were 258 people, aged from
      20 to 40 yr, visiting a health care centre for a check-up. The protocol included:
      a questionnaire (occupation, symptoms of atopy, use of latex goods and possible
      reactions, history of previous surgery), a skin-prick test, and a CAP RAST to
      latex. Atopy was evaluated by a skin-prick test to common allergens and a
      Phadiatop test. RESULTS: Some 6.6% of the study group had either a positive skin
      test or a positive RAST to latex. These subjects had a four-fold higher
      prevalence of symptoms when wearing gloves. The rate of latex sensitization was
      higher by fivefold in subjects with a history of reactions to latex goods and by
      fourfold in atopic subjects. CONCLUSIONS: Because the rate of latex sensitization
      is much higher than the anticipated rate of perioperative reactions due to latex
      allergy, a systematic preoperative screening for latex allergy should not be
      recommended for adults.

PMID- 9146935
TI  - The natural history of Apis-specific IgG and IgG4 in beekeepers.
AB  - BACKGROUND: Most published studies on changes of specific IgG or its subclasses
      as a response to stimuli by allergens have been performed on patients under
      immunotherapy. There are few reports analysing the response to immunoglobulins in
      patients exposed to allergens in their natural habitats. OBJECTIVE: The aim of
      this work was to discover the natural history of Apis specific IgG (IgG-ap) and
      IgG4 (IgG4-ap) levels in beekeepers from the Canary Islands. METHODS: We studied
      242 beekeepers (Bks). We used a questionnaire and measured total IgE and seric
      Apis specific IgE (IgE-ap), IgG-ap and IgG4-ap against Apis mellifera venom.
      RESULTS: All Bks had IgG-ap and IgG4-ap. IgE-ap was positive in 160 Bks (65.6%),
      but only 92 (37.6%) Bks were considered sensitized. IgG-ap and IgG4-ap showed
      significant correlation (r = 0.84); IgE did not correlate with IgG-ap or IgG4-ap.
      There was no seasonal variation in IgG-ap or IgG4-ap. The group of sensitized Bks
      had significantly lower IgG-ap and IgG4-ap levels (P < 0.05). The groups with
      longer beekeeping activity showed significantly higher levels of IgG-ap and IgG4
      ap (P < 0.001). Bks with locals reactions had significantly higher IgG-ap and
      IgG4-ap than Bks who reported systemic reactions (P < 0.05). CONCLUSION: Our
      study showed that IgG-ap and IgG4-ap appear to increase in Bks, either according
      to their beekeeping experience or in subjects with local reactions after bee
      stings.

PMID- 9146936
TI  - Purification and characterization of a soybean hull allergen responsible for the
      Barcelona asthma outbreaks. II. Purification and sequencing of the Gly m 2
      allergen.
AB  - BACKGROUND: A low MW allergen from soybean hull, Gly m 1, with two isoallergens,
      Gly m 1 A and Gly m 1 B, was associated with the asthma outbreaks that occurred
      in Cartagena, Spain. Using sera of asthmatic epidemic patients (AEP) from
      Barcelona, three main soybean hull allergens, two of them with MWs and pIs
      identical to those reported for Gly m 1 A and Gly m 1 B, were identified.
      OBJECTIVE: The purpose of this study was to purify and to study the N-terminal
      amino acid sequence of the third allergen, which has a MW of 8 kDa. METHOD: The
      purification procedure combined the double dialysis method and preparative
      isoelectofocusing (IEF). Specific IgE determination to the fractions obtained
      demonstrated three peaks, one of them corresponding to the 8 kDa allergen. The
      pooled fractions containing this allergen were studied by sodium dodecylsulfate
      polyacrylamide gel electrophoresis (SDS-PAGE), SDS-PAGE/Western blot and
      IEF/Western blot. Only a band with a MW of 8 kDa and a pI of 6 was obtained. Its
      allergenic activity was measured and it was demonstrated that the allergenicity
      of soybean hull correlates with the presence of the 8 kDa allergen. The N
      terminal amino acid sequence of the first 20 amino acids, which was registered at
      the PIR Data Submission as the N-terminal partial sequence of Gly m 2, was
      determined according the Edman degradation method. RESULTS: Gly m 2 N-terminal
      amino acid sequence lacks homology with that reported for the allergen Gly m 1
      but has a homology of 71% with a storage protein from cotyledon of Vigna radiata
      (cow pea) and 64% with a "disease response protein' from Pisum sativum (green
      pea). These results suggest that Gly m 2 in soybeans could protect against
      diseases which affect soybean plants. CONCLUSION: This study demonstrates the
      existence of another soybean hull allergen, Gly m 2, partially responsible for
      the soybean asthma outbreaks that occurred in Barcelona, Spain.

PMID- 9146937
TI  - Anti-asthma effect of an antiviral drug, acyclovir: a clinical case and
      experimental study.
AB  - BACKGROUND: Although acyclovir (9-(2-hydroxyethoxymethyl) guanine) is an
      antiviral drug that inhibits DNA polymerase of herpes virus, we have had the
      experience of an asthmatic patient's peak flow rate being improved by oral
      administration of acyclovir. OBJECTIVE: The aim of this experiment is whether
      acyclovir has anti-asthma effects using an asthma model in guinea-pigs. METHODS:
      The airway response was induced by a single inhalation of calcium ionophore
      A23187 (2 mg/mL). The airway obstruction was estimated by the ratio of expiration
      to inspiration time (E/I). The peribronchial eosinophil infiltration and
      eosinophil influx into bronchoalveolar lavage (BAL) fluid 7 h after the
      inhalation were also examined. To assess the effects of acyclovir (1, 10, and 100
      mg/kg), aminophylline (20 mg/kg) and pemirolast potassium (TBX, 20 mg/kg) on
      A23187-induced asthmatic response, the drugs were intraperitoneally administered
      before the inhalation. RESULTS: The immediate airway obstruction was
      significantly suppressed by acyclovir (10 mg/kg) and aminophylline, whereas
      different doses of acyclovir (1 and 100 mg/kg) and TBX showed only a small
      inhibitory effect on the airway obstruction. On the other hand, the peribronchial
      eosinophilia was most successfully inhibited by TBX. Acyclovir (10 mg/kg) and
      aminophylline also suppressed the eosinophilia significantly. Furthermore,
      acyclovir significantly suppressed eosinophil influx into BAL fluid, whereas
      aminophylline and TBX weakly suppressed the influx. CONCLUSION: These results
      suggest that acyclovir exhibits not only antiviral but also antiasthma activity.

PMID- 9146939
TI  - Microvascular actions of histamine: synergism with leukotriene B4 and role in
      allergic leucocyte recruitment.
AB  - BACKGROUND: Previous studies have shown that antihistamines provide little or no
      protection against the recruitment of leucocytes in allergic inflammation.
      OBJECTIVE: We wanted to examine if threshold doses of histamine can potentiate
      chemoattractant-induced leukocyte adhesion and if complete inhibition of
      histamine-induced microvascular effects is necessary to reduce allergic leucocyte
      recruitment. METHODS: The role of histamine in allergic leucocyte recruitment was
      examined by use of intravital microscopy of the hamster cheek pouch
      microcirculation. RESULTS: We found that topical administration of histamine
      caused a concentration-dependent increase in microvascular permeability in the
      cheek pouch; i.e. 0.3 microM histamine caused no detectable plasma leakage, while
      1 microM and 10 microM histamine resulted in 29 +/- 9.3 and 356 +/- 47 leakage
      sites/cm2 cheek pouch area, respectively. The percentage of postcapillary venules
      with more than five adherent leucocytes (an index of early leucocyte recruitment)
      was 1.1 +/- 0.51% in the control situation, and did not increase significantly
      after stimulation with histamine alone (0.3-10 microM) or with 1 nM leukotriene
      B4 (LTB4). On the other hand, coapplication of 10 microM histamine and 1 nM LTB4
      increased leucocyte adhesion 24-fold. In fact, the 10 times lower dose of
      histamine (1 microM) together with 1 nM LTB4 increased leucocyte adhesion to a
      similar extent (20 fold). The increase in vascular permeability evoked by
      exogenous 10 microM histamine (with or without LTB4), or by histamine released
      from activated mast cells (antigen challenge), was completely reversed by local
      pretreatment with the H1-receptor antagonist mepyramine. This mepyramine
      treatment also abolished the enhanced leucocyte adhesion in response to
      coapplication of histamine and LTB4. Moreover, mepyramine, which had no effect on
      leucocyte recruitment evoked by 3 nM LTB4 per se, reduced antigen-induced
      recruitment of leucocytes to the extravascular tissue by 79.5 +/- 14.8%.
      CONCLUSION: We conclude that threshold concentrations of histamine can strikingly
      potentiate chemoattractant-induced leucocyte responses, and that in order to
      reduce allergic leucocyte recruitment it may be necessary to use antihistamines
      in doses high enough to abolish the microvascular actions of histamine.

PMID- 9146938
TI  - Topical azelastine has a 12-hour duration of action as assessed by histamine
      challenge-induced exudation of alpha 2-macroglobulin into human nasal airways.
AB  - BACKGROUND: Oral anti-histamine drugs are widely used in the treatment of
      seasonal allergic rhinitis. Recently, anti-histamines have become available also
      for topical treatment. OBJECTIVE: The present study, involving healthy subjects,
      examined the effect of topical azelastine on luminal entry of alpha 2
      macroglobulin and symptoms evoked by repeat histamine challenges during 24 h. The
      effect was compared to a clinical dose of the oral anti-histamine cetirizine and
      to placebo treatments. METHODS: Placebo and azelastine (0.254 mg per nasal
      cavity) were delivered as two consecutive actuations per nasal cavity using a
      nasal spray device. Oral placebo and cetirizine (10 mg) were given as single
      doses in a placebo-controlled (double-dummy), double-blind, and cross-over
      design. Histamine-challenges were given 1 h before treatment, and 1, 6, 9, 12,
      and 24 h after each treatment. The nasal mucosal surface was lavaged after each
      challenge. The lavage-fluid levels of alpha 2-macroglobulin were determined to
      assess mucosal exudation of bulk plasma, and nasal symptoms were scored. RESULTS:
      Histamine (40-400 micrograms/mL) produced dose-dependent exudation and symptoms.
      Compared between each treatment and placebo, azelastine and cetirizine reduced
      the 40 and/or 400 micrograms/mL histamine-induced mucosal exudation of plasma
      from 1-12 h after treatment. In addition, cetirizine reduced the 40 micrograms/mL
      histamine-induced mucosal exudation of plasma 24 h after treatment. Differences
      between the two treatments were not evident regarding nasal symptoms. CONCLUSION:
      Histamine challenge-induced mucosal exudation of plasma appears to be a useful
      method for studies of the duration of action of antihistamines. We conclude that
      topical azelastine is suited for b.i.d. therapy and that neither the exudative
      process nor watery secretion may impede the efficacy or the duration of action of
      this nasal drug.

PMID- 9146940
TI  - Localization of Charcot-Leyden crystal protein in individual morphological
      phenotypes of human basophils stimulated by f-Met peptide.
AB  - BACKGROUND: Human basophils undergo anaphylactic degranulation, characterized by
      extrusion of membrane-free granules, and piecemeal degranulation, characterized
      by progressive removal of granule contents in the absence of granule extrusion. F
      Met peptide stimulates a degranulation continuum in human basophils that includes
      both forms of secretion. Charcot-Leyden crystal protein is stored in the granules
      of unstimulated human basophils. OBJECTIVE: The objective of this study was to
      determine the subcellular localization of the Charcot-Leyden crystal protein in
      individual morphological basophil phenotypes that are stimulated by f-Met peptide
      and are associated with secretion. METHODS: A post-embedding immunogold analysis
      was used to detect changes in the subcellular sites of Charcot-Leyden crystal
      protein in human basophils stimulated with f-Met peptide. Human basophils from
      normal donors were purified by countercurrent centrifugal elutriation and Percoll
      density gradients, stimulated to degranulate with 1 micron f-Met peptide (or
      incubated in buffer controls), and recovered for histamine assay, electron
      microscopy and immunogold labelling. Specificity controls included omission of
      the primary antibody and substitution of the primary antibody with non-immune
      normal rabbit IgG or with Charcot-Leyden crystal protein-Sepharose-absorbed
      primary antibody. RESULTS: The results showed new sites of labelling and
      different densities of labelling for Charcot-Leyden crystal protein in
      distinctive basophil phenotypes stimulated by f-Met peptide. New sites for
      Charcot-Leyden crystal protein included nucleus, cytoplasm, degranulation
      channel, degranulation channel membrane, plasma membrane, and a newly recognized
      granule population similar to primary granules in eosinophils. These new sites,
      as well as previously documented sites of Charcot-Leyden crystal protein
      (granules, intragranular Charcot-Leyden crystals, cytoplasmic vesicles) showed
      variable labelling when analysed by phenotype. Other sites (besides intragranular
      Charcot-Leyden crystals) of formed Charcot-Leyden crystals included cytoplasm,
      degranulation channel, extracellular space and, rarely, nucleus. Analysis of
      cytoplasmic vesicles, total granules and altered granules, and gold particles in
      subcellular compartments in seven identifiable phenotypes revealed that f-Met
      peptide stimulated human basophils to empty their granules by transporting
      Charcot-Leyden crystal protein in vesicles to the plasma membrane in the absence
      of granule extrusion in cells exhibiting piecemeal degranulation. In cells
      exhibiting anaphylactic degranulation, gold-labelled Charcot-Leyden crystals were
      extruded to the cells' exterior in concert with granule particles and concentric
      dense membranes contained within granules. Completely degranulated cells had a
      high density of plasma membrane gold label that was associated with numerous gold
      laden endocytotic cytoplasmic vesicles. Basophils reconstituted their main
      granule population, within which Charcot-Leyden crystals resided, in part by
      endocytosis of previously released plasma membrane-bound Charcot-Leyden crystal
      protein. Completely recovered cells displayed decreased Charcot-Leyden crystal
      protein labelling of the plasma membrane and vesicle compartments, the presence
      of a highly labelled new granule subset that resembled Charcot-Leyden crystal
      protein-containing primary granules in eosinophils, and the highest density of
      granule and intragranular Charcot-Leyden crystal gold labelling of all phenotypes
      that developed after stimulation. CONCLUSION: Seven individual f-Met peptide
      activated human basophil phenotypes labelled by an ultrastructural immunogold
      method to detect subcellular sites of Charcot-Leyden crystal protein showed
      changing distributions of this protein which document the capability of human
      basophils to undergo complex release and recovery reactions that may be pertinent
      to the functions of Charcot-Leyden crystal protein and the capabilit

PMID- 9146941
TI  - Haematological reference ranges for schoolchildren.
AB  - There are few reports of reference ranges for haematological values in school age
      children and most studies extend over a small age range or have excluded a
      considerable proportion of the study population in an effort to omit those with
      haemoglobinopathies or anaemia. Blood samples from 2135 children aged 4-19 years,
      from randomly selected schools, were analysed by automated counter. Reference
      ranges for red cell, white cell and platelet indices are provided from the
      results. Median haemoglobin and red blood cell count values for girls and boys
      rose together with increasing age, up to 12 years, but then diverged. Girls had a
      higher platelet count than boys. Mean platelet volume rose with age and was
      inversely related to the platelet count. Plateletcrit fell with age but in girls
      there was a peri-pubertal peak. Total leucocyte count fell with age. The upper
      limits for total leucocyte count in this study are approximately 2 x 10(9) lower
      than those quoted in modern haematology textbooks. Lymphocyte, eosinophil and
      basophil counts fell with age with little difference between the sexes.
      Neutrophil and monocyte counts were similar for younger girls and boys but
      diverged in the older children with the older girls having higher values than
      boys.

PMID- 9146942
TI  - Pulse oximetry in a cohort study of sickle cell disease.
AB  - Oxygen saturation was determined by pulse oximetry in a representative sample of
      Jamaican patients with steady-state sickle cell disease in a cohort study from
      birth. There were 220 with homozygous sickle cell (SS) disease and 142 with
      sickle cell-haemoglobin C (SC) disease aged 9-18 years, and 122 with a normal
      haemoglobin (AA) genotype aged 15-18 years. Pulse oximetry (SpO2) values were
      lower in SS disease (mean [95% confidence interval], 92.5 [92.0-93.0]) than in SC
      disease (96.7[96.5-96.9]) or AA controls (97.1 [96.8-97.3]). Inhalation of 100%
      oxygen in SS patients with O2 saturations below 90% consistently increased
      saturation to 99-100%. In SS disease, SpO2 correlated positively with haemoglobin
      and fetal haemoglobin and negatively with reticulocyte counts but not with MCHC,
      MCV or bilirubin level. Mean SpO2 in SS subjects with a normal alpha globin gene
      complement (mean [SD], 91.7 [3.9]%) was lower than in heterozygotes (93.4 [4.0]%)
      or homozygotes (96.1 [3.0]%) for alpha+ thalassaemia, the effects of alpha
      thalassaemia not being explained by differences in haemoglobin or MCHC. In SS
      disease, SpO2 levels were not associated with age (within this age range), sex,
      number of sick clinic visits or number of hospital admissions. Higher SpO2 levels
      were associated with greater height and weight, more frequent painful crises and
      less frequent acute chest syndrome, but these associations were not significant
      after adjustment for haemoglobin level. Desaturation is common in steady-state SS
      disease and knowledge of the individual's steady-state value may be important in
      the interpreting low values during acute complications.

PMID- 9146943
TI  - Infantile megaloblastosis secondary to maternal vitamin B12 deficiency.
AB  - We reviewed six cases of infantile megaloblastosis secondary to maternal vitamin
      B12 deficiency, the most common cause of infantile megaloblastosis in our
      institution. Two patients had long-term neurological sequelae, with a further
      patient remaining abnormal but at short follow-up. In 50% of cases the mother was
      asymptomatic, with subtle or no peripheral blood abnormalities, having early
      pernicious anaemia. Any infant which fails to thrive, with progressive
      neurological deterioration and haematological cytopenias should have their
      vitamin B12 and folate status rapidly assessed. This is one of the few
      potentially reversible causes of failure to thrive and neurological
      deterioration. Early diagnosis and treatment may prevent significant long-term
      sequelae.

PMID- 9146944
TI  - Dependency of MCV and haemoglobin concentration on plasma vitamin B12 levels in
      relation to sex and age.
AB  - In a retrospective study of 872 men and 1474 women we determined the relationship
      between serum vitamin B12 concentration and mean values for Hb and MCV, which
      were known for 68% of the men and 72% of the women. In both sexes there was a
      distinct decrease in the mean Hb at serum vitamin B12 concentrations < 0.05
      nmol/l. However, the mean MCV was already raised by 4-5 fl at serum vitamin B12
      levels < 0.16 nmol/l in men and < 0.11 nmol/l in women, and the percentage of
      patients with macrocytosis (defined as MCV > 100 fl) also increased significantly
      at these levels. To find out whether these relationships were age-dependent, male
      and female patients were split into groups of 20-70 years old and older persons.
      The mean MCV in men aged 20-70 years increased at a serum vitamin B12 level <
      0.16 nmol/l, whereas in older men an increase in mean MCV occurred only at
      vitamin B12 levels < 0.11 nmol/l. In women, the mean MCV for both age groups
      increased significantly at a serum vitamin B12 level < 0.11 nmol/l. We conclude
      that haematological signs of B12 deficiency arise at different serum vitamin B12
      concentrations in men and women and that only in men is there an age dependency.

PMID- 9146945
TI  - Application of the multi-colour FISH to interphase nuclei and metaphase spreads
      for simultaneous examination of monosomy 7 and trisomies 8 and 11 in acute
      myelocytic leukaemia (AML).
AB  - We have used the multi-colour (three) fluorescence in situ hybridization (FISH)
      technique based on the ratio labelling for the detection of monosomy 7 and
      trisomies 8 and 11 in 13 cases of acute myeloid leukaemia (AML). Two out of the
      13 AML cases showed monosomy 7 and two out of the remaining cases exhibited
      trisomy 8 in interphase nuclei. Three of these results were confirmed by
      metaphase-FISH study. Trisomy 11 was not found either by the interphase FISH
      study or in the metaphase FISH study. These results demonstrate the potential
      power of multi-colour FISH using ratio labelling to produce more fluorescein
      colour in interphase nuclei for the detection of aneuploidies in leukaemia.

PMID- 9146946
TI  - Effects of in vitro and in vivo cytokine treatment, leucapheresis and irradiation
      on the function of human neutrophils: implications for white blood cell
      transfusion therapy.
AB  - Treatment of human polymorphonuclear leucocytes (PMNL) separated by density
      sedimentation (DS) from normal donors (PMNL-NL-DS) with interferon-gamma (IFN
      gamma) + granulocyte colony-stimulating factor (G-CSF) lessens the damage caused
      by isolation and irradiation. We have studied granulocyte-macrophage colony
      stimulating factor (GM-CSF) in this system, as well as the behaviour of PMNL
      collected by continuous flow leucapheresis (CFL) from donors treated with G-CSF
      (PMNL-GCSF-CFL). After isolation, PMNLs were treated with IFN-gamma + G-CSF, GM
      CSF or IFN-gamma + G-CSF + GM-CSF, irradiated with 0 or 30 Gy and studied after 0
      and 20 h in cell culture. All regimens reduced apoptosis of PMNL-NL-DS. Killing
      of Candida albicans by 20-h-old PMNL-NL-DS was best preserved by IFN-gamma + G
      CSF treatment. A similar pattern of results was obtained for assays of PMNL-NL-DS
      chemotaxis and superoxide production. There was a consistent trend toward reduced
      function after irradiation in all assays. PMNL-GCSF-CFL less often demonstrated
      the morphological features of apoptosis, and this was further reduced by cytokine
      regimens containing IFN-gamma + G-CSF. In assays of C. albicans killing and
      chemotaxis, 20-h-old untreated PMNL-GCSF-CFL performed as well as freshly
      isolated PMNL-GCSF-CFL. PMNL-GCSF-CFL showed decay in CD11b (CR3), CD16 (Fc gamma
      III) and CD64 (Fc gamma R1) expression after 20 h in cell culture, but treatment
      with IFN-gamma + G-CSF preserved expression. There was a trend toward reduced
      function after radiation. Comparison of PMNL-GCSF separated by CFL and DS
      demonstrated that CFL itself is a strong inducer of the morphological features of
      apoptosis. This study shows that while separation by CFL, and irradiation are
      damaging to PMNLs, damage may be reduced by use of cytokines.

PMID- 9146947
TI  - Improved dextran preparation of human leucocytes for chemiluminescence analysis
      of the oxidative burst of polymorphonuclear cells.
AB  - An improved method for the preparation of leucocyte-rich plasma from human blood
      samples for chemiluminescence (CL) analysis is described. Heparinized blood is
      layered over 4% dextran in a ratio of 1:1 (v/v). The leucocyte-rich plasma is
      obtained after a 1 h sedimentation of the erythrocytes. When compared with the
      plasma obtained by the usual method of mixing blood with dextran, the residual
      red cell count was reduced. On the other hand, the index of phagocytosis (peak
      values of activated phagocytosis/spontaneous phagocytosis) was increased. This is
      caused by increased spontaneous CL activity after mixing blood with dextran,
      which can activate leucocytes. Such activation was observed both in plasma
      samples and in whole blood samples when measured immediately after dextran
      addition or after 1 h incubation with dextran.

PMID- 9146948
TI  - Dose titration during anti-thymocyte globulin therapy: monitoring by CD3 count or
      total lymphocyte count?
AB  - Anti-thymocyte globulin (ATG) is extensively used for both prophylaxis and
      treatment of rejection episodes in renal transplantation, but it is expensive and
      potentially hazardous. We report the utility of therapeutic monitoring by the
      readily available total lymphocyte count, compared with the more complex and
      expensive assay of CD3 counts by flow cytometry in eight renal transplant
      patients receiving ATG. Aiming for an absolute CD3 count of 0.2-0.5 x 10(9)/l, it
      was possible to reduce the mean daily dose of ATG from the recommended 2.5
      mg/kg/d to a mean of 1.6 mg/kg/d. Analysis of simultaneously taken total
      lymphocyte counts showed that the same dose reductions could have been made if
      the target for therapeutic effect had been a total lymphocyte count of < 0.3 x
      10(9)/l. Anti-rejection therapy was successful in all cases, with satisfactory
      graft function at 6-9 months post-therapy. Lower than recommended doses of ATG
      proved effective prophylaxis and treatment of renal allograft rejection, with
      considerable cost savings. A simple protocol may be followed titrating dose
      against total lymphocyte count, provided it remains below 0.3 x 10(9)/l. CD3
      estimation can be reserved for those times when the total lymphocyte count rises
      to 0.3 x 10(9)/l or above.

PMID- 9146949
TI  - Immunological abnormalities of chronic large granular lymphocytosis.
AB  - Chronic large granular lymphocytosis is a relatively common condition and
      comprises a clinically heterogenous group of patients. Phenotypically these can
      be divided into CD3+ (T cell) and CD3-(NK cell) expansions. They are
      characterized by a benign clinical course and a mild lymphocytosis, though a
      specific subgroup have a history of auto-immune disease and cytopenias. In order
      to develop a better understanding of the immunological abnormalities associated
      with this condition we examined systematically serum samples from 92 such
      patients for the presence of auto-antibodies, acute phase proteins and
      immunoglobulin levels. Auto-antibodies were found in 34% of patients and
      rheumatoid factor in 26%, though only half of these had active arthritis. Anti
      neutrophil antibodies were negative in all cases. Quantitative immunoglobulin
      abnormalities were frequent with a distinct paraprotein present in three
      patients. The high incidence of multiple immunological abnormalities in these
      patients ranged from polyclonal hypergammaglobulinaemia and auto-antibodies
      through to monoclonal gammopathy. The aetiology of these abnormalities was
      unclear and undoubtedly complex, and should necessarily form part of the
      diagnostic investigations for all patients with persistent large granular
      lymphocyte expansions.

PMID- 9146950
TI  - Serum-free culture of human megakaryocyte progenitors.
AB  - A serum-free method for the culture of megakaryocyte progenitor cells (burst
      forming units megakaryocyte, BFU-Mk) from human bone marrow is described, using
      recombinant cytokines (interleukin[IL]-3, IL-6, IL-11 and stem cell factor [SCF])
      to provide megakaryocyte colony-stimulating activity. IL-3 alone, but not IL-6,
      IL-11 or SCF alone, promoted BFU-Mk formation. The combination of IL-3 with IL-11
      or with IL-6+SCF was necessary for optimal maturation of the megakaryocytes. No
      significant difference in BFU-Mk numbers was found between the combinations of IL
      3+IL-11 and IL-3+IL-6+SCF. The development of BFU-Mk was found to be maximal at
      12-14 d. Using these conditions, normal ranges for human bone marrow BFU-Mk were
      derived which may provide the basis for studying megakaryocyte colony growth in
      pathological conditions.

PMID- 9146951
TI  - Diagnosis strategies in activated protein C resistance: is genotyping still
      necessary?
AB  - Resistance to activated protein C (APC) is due, in most cases, to a G to A
      mutation at nucleotide 1691 of factor V (FV) gene (the Leiden mutation). This
      inherited abnormality is now considered to be the major hereditary cause
      associated with an elevated risk of thrombosis. For this reason, laboratories are
      faced with an increasing number of samples referred for APC resistance diagnosis.
      This could have serious economic consequences and a comprehensive laboratory
      screening strategy for APC resistance is necessary. An original DNA assay based
      on denaturing gradient gel electrophoresis (DGGE) was designed in our laboratory.
      During a first period we systematically performed DNA analysis and compared the
      results with phenotypic assays. Using the modified functional test with a 1:5
      predilution of plasmas, the cut-off value for APC resistance ratio was 2.6 in our
      sample. Among 94 consecutive patients referred to our laboratory we found a clear
      cut-off between the APC resistance ratio obtained for normal and abnormal
      individuals. The modified test had a predictive value of 1.0 found by a cut-off <
      or = 2.6 for the heterozygote FV Leiden. This obviates the necessity of
      genotyping subjects with a normal phenotype. Among patients with an abnormal
      phenotype we were able to fully discriminate between homozygous and heterozygous
      patients using a cut-off value of 1.5. Nevertheless, our results demonstrate
      that, because of false-positive results such as lupus anticoagulant, genotyping
      is still indicated for patients with an abnormal ratio determined with the
      modified APC resistance test. The strategy described here allows us to safely
      lower the number of samples analysed by DGGE.

PMID- 9146952
TI  - Acute auto immune haemolytic anaemia secondary to hepatitis A infection.
AB  - Auto immune haemolytic anaemia has been described in association with a variety
      of hepatotropic viruses, in particular cytomegalovirus, Epstein-Barr virus and
      hepatitis B. There is a well-recognized association between chronic active
      hepatitis and auto immune haemolytic anaemia. We present the first reported case
      of acute hepatitis A which resulted in a fall in haemoglobin concentration from
      14.6 to 4.5 g/dl due to an acute haemolytic anaemia with an associated rise in
      bilirubin from 149 to 960 mumol/l.

PMID- 9146953
TI  - Successful use of granulocyte colony-stimulating factor to correct neutropenia in
      chronic lymphocytic leukaemia.
AB  - A case of wound infection secondary to profound neutropenia associated with
      chronic lymphocytic leukaemia is described. Both the neutropenia and infection
      resolved with the use of granulocyte colony-stimulating factor. This agent may be
      useful in other similar patients.

PMID- 9146954
TI  - Fludarabine-induced tumour lysis in low-grade non-Hodgkin's lymphoma.

PMID- 9146955
TI  - Letter from America: this little piggy went to market.

PMID- 9146956
TI  - Interference of blood leucocytes in the measurements of immature red cells by two
      different (semi-) automated flow-cytometry technologies.

PMID- 9146957
TI  - A bank of protein family patterns for rapid identification of possible functions
      of amino acid sequences.
AB  - A method and software tool to develop patterns of protein families has been
      designed. These patterns are intended for the identification of local
      similarities in arbitrary amino acid sequences with proteins of the SWISS-PROT
      bank. The method is based on the physical, chemical and structural properties of
      amino acids. It assembles a 'best set' of elements (a pattern) for a given group
      of aligned related proteins. These elements provide discrimination between
      proteins of a family and representatives of other families or random sequences.
      The method combines the advantages of BLOCKS (automatic generation of multiple
      elements for protein groups), PROSITE (simplicity of element presentation) and
      matrices/profiles (different distinctions between amino acids for different
      positions of aligned sequences). Using our method, a data bank of protein family
      patterns, PROF_PAT, is produced. This data bank is based on the 27,752 amino acid
      sequences of SWISS-PROT bank release 24. The characteristics of patterns of 743
      related protein groups are described. The results of comparisons of PROF_PAT
      patterns with the proteins of the SWISS-PROT bank are discussed.

PMID- 9146958
TI  - Elasticities in Metabolic Control Analysis: algebraic derivation of simplified
      expressions.
AB  - MOTIVATION: Metabolic Control Analysis is one of many disciplines that make use
      of scaled derivatives. In particular, 'elasticities' are used to quantify the
      effect of an effector or substrate concentration on an enzyme rate under locally
      specified conditions. Normally an algebraic expression for the elasticity of an
      enzyme is obtained by differentiating its rate law, multiplying by the effector
      concentration and dividing by the rate law itself: this results in considerable
      expression expansion, and when the results are subsequently simplified it is
      often at the expense of biological comprehensibility. RESULTS: We present a novel
      algorithm which not only circumvents the expression expansion, but preserves an
      elegant separation of the components in enzyme behaviour. Easily implemented, and
      producing gains in both performance and numerical precision, the algorithm is
      potentially applicable to a number of existing packages. It also greatly assists
      the manual derivation and evaluation of elasticities, allowing the elasticity of
      even quite complex enzyme systems to be written by inspection.

PMID- 9146959
TI  - Detection of significant patterns by compression algorithms: the case of
      approximate tandem repeats in DNA sequences.
AB  - MOTIVATION: Compression algorithms can be used to analyse genetic sequences. A
      compression algorithm tests a given property on the sequence and uses it to
      encode the sequence: if the property is true, it reveals some structure of the
      sequence which can be described briefly, this yields a description of the
      sequence which is shorter than the sequence of nucleotides given in extenso. The
      more a sequence is compressed by the algorithm, the more significant is the
      property for that sequence. RESULTS: We present a compression algorithm that
      tests the presence of a particular type of dosDNA (defined ordered sequence-DNA):
      approximate tandem repeats of small motifs (i.e. of lengths < 4). This algorithm
      has been experimented with on four yeast chromosomes. The presence of approximate
      tandem repeats seems to be a uniform structural property of yeast chromosomes.

PMID- 9146960
TI  - LASSAP, a LArge Scale Sequence compArison Package.
AB  - MOTIVATION: This paper presents LASSAP, a new software package for sequence
      comparison. LASSAP is a programmable, high-performance system designed to raise
      current limitations of sequence comparison programs in order to fit the needs of
      large-scale analysis. LASSAP provides an API (Application Programming Interface)
      allowing the integration of any generic pairwise-based algorithm. RESULTS:
      Whatever pairwise algorithm is used in LASSAP, it shares with all other
      algorithms numerous enhancements such as: (i) intra- and inter-databank
      comparisons; (ii) computational requests (selections and computations are
      achieved on the fly); (iii) frame translations on queries and databanks; (iv)
      structured results allowing easy and powerful post-analysis; (v) performance
      improvements by parallelization and the driving of specialized hardware. LASSAP
      currently implements all major sequence comparison algorithms (Fasta, Blast,
      Smith/Waterman), and other string matching and pattern matching algorithms.
      LASSAP is both an integrated software for end-users and a framework allowing the
      integration and the combination of new algorithms. LASSAP is used in different
      projects such as the building of PRODOM, the exhaustive comparison of yeast
      sequences, and the subfragments matching problem of TREMBL.

PMID- 9146961
TI  - Using video-oriented instructions to speed up sequence comparison.
AB  - MOTIVATION: This document presents an implementation of the well-known Smith
      Waterman algorithm for comparison of proteic and nucleic sequences, using
      specialized video instructions. These instructions, SIMD-like in their design,
      make possible parallelization of the algorithm at the instruction level. RESULTS:
      Benchmarks on an ULTRA SPARC running at 167 MHz show a speed-up factor of two
      compared to the same algorithm implemented with integer instructions on the same
      machine. Performance reaches over 18 million matrix cells per second on a single
      processor, giving to our knowledge the fastest implementation of the Smith
      Waterman algorithm on a workstation. The accelerated procedure was introduced in
      LASSAP--a LArge Scale Sequence compArison Package software developed at INRIA-
      which handles parallelism at higher level. On a SUN Enterprise 6000 server with
      12 processors, a speed of nearly 200 million matrix cells per second has been
      obtained. A sequence of length 300 amino acids is scanned against SWISSPROT R33
      (1,8531,385 residues) in 29 s. This procedure is not restricted to databank
      scanning. It applies to all cases handled by LASSAP (intra- and inter-bank
      comparisons, Z-score computation, etc.

PMID- 9146962
TI  - Sequential and parallel algorithms for DNA sequencing.
AB  - MOTIVATION: Reconstruction of the original DNA sequence in the sequencing by the
      hybridization approach (SBH) requires computational support due to a large number
      of possible combinations. One can notice a lack of algorithms admitting false
      negative data and giving in addition all possible solutions. RESULTS: In this
      paper, a new method of sequencing has been proposed. An algorithm based on its
      idea (for the general case, when some data are missing, like in the real
      experiment) has been implemented and tested. Authentic DNA sequences have been
      used for testing. A parallel version of the algorithm has also been implemented
      and tested. The quality of the reconstruction is satisfactory for the library of
      oligonucleotides of length between 8 and 12, and 100, 200 and 300 bp long
      sequences. A way to a further decrease in the computation time is also suggested.

PMID- 9146963
TI  - Computer program for the equations describing the steady state of enzyme
      reactions.
AB  - MOTIVATION: The derivation of steady-state equations is frequently carried out in
      enzyme kinetic studies. Done manually, this becomes tedious and prone to human
      error. The computer programs now available which are able to accept reaction
      mechanisms of some complexity are focused only on the strict steady-state
      approach. RESULTS: Here we present a computer program called REFERASS, with a
      short computation time and a user-friendly format for the input and output files,
      able to derive the strict steady-state equations and/or those corresponding to
      the usual assumption that one ore more of the reversible steps are in rapid
      equilibrium. This program handles enzyme-catalysed reactions with mechanisms
      involving up to 255 enzyme species connected by up to 255 reaction steps, subject
      to limits imposed by the memory and disk space available.

PMID- 9146964
TI  - A key for freshwater invertebrates using fuzzy logic.
AB  - MOTIVATION: This paper summarizes a biological key using a fuzzy logic expert
      system. This approach allows the user to make some errors, be uncertain about
      some answers and not answer questions if unsure, but have an opportunity to
      identify unknown specimens correctly. This approach was adopted in order to
      develop a 'forgiving' key for users with little or no prior knowledge of
      identification. The system was implemented using a multi-media expert system
      builder, 'Matcher', operating in a Microsoft Windows environment. RESULTS: The
      paper reports the design issues for a key to identify freshwater invertebrates to
      family level and describes the types of questions used within the key, the fuzzy
      inference engine, the structure of the system and the methodology adopted for
      testing it. Following this, an empirical test is reported of the hypothesis that
      a fuzzy logic expert system can improve identification accuracy for a sample of
      intended users. Finally, the discussion considers the practicalities of using
      such a system as an aid to organism identification.

PMID- 9146965
TI  - Hopper: software for automating data tracking and flow in DNA sequencing.
AB  - MOTIVATION: Genome-scale DNA sequencing is a multistep process in which large
      numbers of small template clones are propagated, purified, sequenced and analyzed
      on acrylamide gels. A significant challenge to these projects is the scale at
      which the data handling must be done. Hence, large-scale sequencing facilities
      will benefit from tracking template DNA information (purification methods,
      reaction and electrophoresis conditions) in a systematic fashion. A lack of
      software tools that support automated sample entry, and automatic data storage,
      retrieval and analysis are a major hindrance to recording and using laboratory
      workflow information to monitor the overall quality of data production. RESULTS:
      The UNIX file system has been used to prototype automation of the flow of data
      from the ABI sequencer to a data repository. Data are automatically processed by
      a central Perl program, Hopper, which runs a series of programs that analyze data
      quality (read length estimate, fraction of indeterminate bases, and number of
      contaminating and repetitive sequences), assemble shotgun sequence data, and
      generates simple reports describing the results.

PMID- 9146966
TI  - Application of a deductive database system to search for topological and similar
      three-dimensional structures in protein.
AB  - A deductive database system PACADE (Protein Atomic Coordinate Analyzer with
      Deductive Engine) has been developed for protein structure analysis. With this
      system, super-secondary structures described in logical and declarative rules can
      be retrieved effectively. For protein structure analysis, comparison of local
      structures in different proteins is a necessary mean. A function to search for
      similar structures has, therefore, been added to the PACADE system. We describe
      herein the result of searches for the same topological structures and three
      dimensionally similar ones. A user of PACADE can select these two levels of
      similarity by changing parameters. This function enables the inference system to
      retrieve similar structures, according to the restraints of variables defined by
      the user. Similar super-secondary structures among proteins can be searched for
      automatically, which is useful for protein structure analysis. The retrieved
      similar super-secondary structures can serve as criteria for protein spatial
      alignment.

PMID- 9146967
TI  - Scoring hidden Markov models.
AB  - MOTIVATION: Statistical sequence comparison techniques, such as hidden Markov
      models and generalized profiles, calculate the probability that a sequence was
      generated by a given model. Log-odds scoring is a means of evaluating this
      probability by comparing it to a null hypothesis, usually a simpler statistical
      model intended to represent the universe of sequences as a whole, rather than the
      group of interest. Such scoring leads to two immediate questions: what should the
      null model be, and what threshold of log-odds score should be deemed a match to
      the model. RESULTS: This paper analyses these two issues experimentally. Within
      the context of the Sequence Alignment and Modeling software suite (SAM), we
      consider a variety of null models and suitable thresholds. Additionally, we
      consider HMMer's log-odds scoring and SAM's original Z-scoring method. Among the
      null model choices, a simple looping null model that emits characters according
      to the geometric mean of the character probabilities in the columns modeled by
      the hidden Markov model (HMM) performs well or best across all four
      discrimination experiments.

PMID- 9146968
TI  - Search the Human cDNA Database at TIGR.
AB  - MOTIVATION: The Human cDNA Database (HCD) at the Institute for Genomic Research
      (TIGR) is the most complete, non-redundant and structured collection of human
      expressed DNA sequences available to date. Sequences and other data can be
      retrieved by users having opened an account at HCD/TIGR. A HCD search involves
      composing and sending queries one by one and this can become time consuming if
      many queries must be sent. Moreover, a large amount of time is required
      thereafter to process the results. RESULTS: The HCDSearch system described here
      automatically composes and sends the queries by e-mail using information provided
      in a text file; it also greatly accelerates the processing of results, generating
      lists of HCD numbers and library identifiers in a format that renders them very
      easy to examine. The programs run on Unix platforms.

PMID- 9146969
TI  - Software for DNA sequencing by hybridization.
AB  - Sequencing by hybridization (SBH) is a promising alternative approach to DNA
      sequencing and mutation detection. Analysis of the resolving power of SBH
      involves rather difficult combinatorial and probabilistic problems, and sometimes
      computer simulation is the only way to estimate the parameters and limitations of
      SBH experiments. This paper describes a software package, DNA-SPECTRUM, which
      allows one to analyze the resolving power and parameters of SBH. We also
      introduce the technique for visualizing multiple SBH reconstructions and describe
      applications of DNA-SPECTRUM to estimate various SBH parameters. DNA-SPECTRUM is
      available at http://www-hto.usc.edu/software/sbh/index. html.

PMID- 9146970
TI  - Congenital thoracic masses: imaging features in the adult.
AB  - Congenital anomalies in the adult thorax are frequently asymptomatic and may
      remain undetected for many years. Whether they then become symptomatic or are
      discovered as an incidental finding on an imaging study obtained for unrelated
      reasons, thoracic anomalies may appear as masses or contour abnormalities that
      mimic other pathology, particularly neoplastic disease. The aim of this review is
      to discuss and illustrate a wide variety of congenital thoracic anomalies that
      can potentially present as a mass in the thorax. For ease of discussion, lesions
      are classified under numerous headings, including congenital lung anomalies
      caused by bronchopulmonary malformations and anomalies of pulmonary vasculature,
      vascular anomalies of the great vessels, diaphragmatic anomalies, and congenital
      masses of the chest wall. The appearance of these congenital lesions on chest
      radiographs and other imaging modalities such as CT, MRI, and angiography are
      illustrated, with emphasis on features that can distinguish these lesions from
      other intrathoracic masses.

PMID- 9146971
TI  - Glomerulonephritis: roles for lipoxygenase pathways in pathophysiology and
      therapy.

PMID- 9146972
TI  - Involvement of complement components in renal disease.
AB  - The complement system is a critical element of innate immunity whose role in
      renal physiology and disease is illustrated by the following observations: (1) a
      deficiency or inhibition of a complement regulatory protein results in renal
      tissue damage; (2) inhibition of complement activation (with cobra venom factor
      or sCR1), or in C6-deficient rats, attenuates complement-mediated tissue
      destruction; and (3) ongoing glomerular disease has been associated with the
      deposition/expression of complement proteins in glomerular or tubular structures
      and the excretion of C5b-9 and CD59 proteins. Complement activation by cellulosic
      membranes results in the production of C5a, which has now been shown to provoke
      most of the same inflammatory responses observed during hemodialysis. Controlling
      the dose of C5a given during dialysis, by controlling blood flow rates or
      membrane types, may have an impact on patient health. Finally, lessons learned in
      the xenotransplant setting suggest that complement activation can be effectively
      controlled to limit inflammation (with sCR1 or anti-C5 monoclonal antibodies).
      Recent developments in this area may lead to new therapeutic approaches to deal
      with the complex etiology of renal disease.

PMID- 9146973
TI  - Sodium balance in renal failure.
AB  - Sodium balance in patients with renal failure varies with the severity and
      clinical manifestations of renal disease. Progressive chronic renal insufficiency
      is typified by an adaptive increase in the sodium excretion rate per nephron as
      the total glomerular filtration rate declines. This increase is caused, at least
      in part, by the effect of atrial natriuretic peptide and other natriuretic
      peptides, whose release is augmented in the setting of volume expansion and renal
      failure. However, exogenous administration of natriuretic peptides in clinical
      chronic and acute renal disease does not consistently increase renal sodium
      excretion. As the glomerular filtration rate progressively declines towards end
      stage renal disease, total renal sodium excretion eventually decreases, and
      extracellular volume expansion, hypertension, and edema develop. Sodium removal,
      induced by high dose diuretics or via convective ultrafiltration during dialysis,
      is necessary to decrease the extracellular volume to normal.

PMID- 9146974
TI  - Proteinuria and progression of renal disease: therapeutic implications.
AB  - The relationship between proteinuria and progression of renal disease has long
      been an issue of debate. The present review deals with some of the recent
      publications on this topic. New concepts are emphasized: the possible causal role
      of proteinuria in the pathophysiology of progressive renal function loss, and the
      decrease in urinary protein loss at the beginning of renoprotective therapy as a
      predictor of renal function outcome during this treatment.

PMID- 9146975
TI  - The diagnosis of renal involvement in non-insulin-dependent diabetes mellitus.
AB  - Efforts aimed at early detection and effective treatment and prevention of renal
      involvement in non-insulin-dependent diabetes mellitus are needed to limit the
      increasing social burdens of end-stage renal disease and related complications.
      Microalbuminuria seems to meet all the criteria required for screening of early
      renal disease (incipient nephropathy) and detection of patients at increased
      cardiovascular risk. Histologic examination is needed to ensure diagnosis of
      overt diabetic nephropathy in patients with macroalbuminuric non-insulin
      dependent diabetes mellitus without retinopathy. Regular screening for micro- and
      macroalbuminuria ensures that renal and extrarenal complications may be
      identified early and that preventive intervention therapy is instituted,
      including good metabolic control and raised blood pressure correction.
      Preliminary evidence suggests that this is a very cost-effective use of health
      care resources.

PMID- 9146976
TI  - Genetics of the renin-angiotensin system and renal disease: a progress report.
AB  - The genes of the renin-angiotensin system and their relation to renal diseases
      are of great interest. The number of studies examining the role of polymorphism
      in these genes in development or progression of renal diseases has increased
      nearly logarithmically, but results remain conflicting. Evidence is increasing
      that progression of renal disease is more rapid in DD-homozygotes of the
      angiotensin-converting enzyme gene polymorphism, but other relationships have not
      been solidly established.

PMID- 9146977
TI  - Renal implications of arterial hypertension.
AB  - Renal vascular damage caused by arterial hypertension participates in alterations
      of the systemic vascular function and structure. Nephrosclerosis seems to run in
      parallel with the systemic atherosclerosis that accounts for the increased
      cardiovascular morbidity and mortality seen in hypertensive patients. Parameters
      indicating the existence of an alteration in renal function (increased serum
      creatinine, proteinuria and microalbuminuria) are independent predictors for an
      increased cardiovascular morbidity and mortality. Hence, parameters of renal
      function must be considered in any stratification of cardiovascular risk in
      hypertensive patients.

PMID- 9146978
TI  - Ischaemic renal injury.
AB  - Ischaemic renal injury is becoming one of the main causes of end-stage renal
      failure. The appearance of new diagnostic methods, as well as the evidence that
      surgery or percutaneous transluminal angioplasty techniques are capable of
      inducing a significant degree of recovery in a subset of patients, are
      encouraging events. The identification of the precise cellular pathogenetic
      mechanisms of ischaemic injury is an area for future research.

PMID- 9146979
TI  - Pathophysiology of hypertension.

PMID- 9146980
TI  - Myocyte cell death and ventricular remodeling.
AB  - The recognition that cell death in the myocardium is not only necrotic in nature
      but is also mediated by activation of the suicide program of myocytes has raised
      several questions concerning the magnitude of this phenomenon, and whether these
      two distinct forms of cell death are disease-dependent or coexist in the
      pathologic heart. Additionally, the times required for the completion of
      apoptotic and necrotic myocyte cell death are unknown, making the analysis of
      their respective rates in the myocardium impossible at present. The documentation
      that mechanical forces in vitro, mimicking diastolic Laplace overloading in vivo,
      can transmit a death signal to myocytes suggests that programmed cell death may
      be triggered in the stressed myocardium independently from the etiology of the
      overload. Because increasing pressure or volume loads, or both, in the failing
      heart induce myocyte hypertrophy and proliferation, a challenging question is
      whether the induction of genes regulating these cellular growth processes may
      activate programmed cell death as well. Finally, the identification of the
      mechanisms responsible for the translation of a diffuse environmental condition
      into a death signal in a limited number of cells scattered across the ventricular
      wall is a major challenge of future research.

PMID- 9146981
TI  - Kidney damage in 'benign' essential hypertension.
AB  - During the past 12 months additional evidence has emerged from observational
      studies indicating that high blood pressure is an important independent predictor
      of incident renal damage, progression of existing renal disease, and morbidity
      and mortality in patients with renal failure. Several of these studies suggest
      that elevation of systolic blood pressure is a stronger predictor of risk than a
      corresponding increase in diastolic blood pressure. Furthermore, the relationship
      between blood pressure and incident renal disease appears to be positive and
      continuous throughout the entire spectrum of blood pressure, including in the
      'normotensive' range. Recent clinical trial experience in patients with renal
      insufficiency of diverse etiology supports the beneficial effect of treatment
      with angiotensin-converting enzyme inhibitors noted in earlier studies confined
      to patients with type II diabetes. Ongoing trials should help clarify optimal
      choice of antihypertensive medications and goals for reduction of blood pressure
      in prevention of renal disease. In the interim, two new guidelines for management
      of hypertension in patients with existing renal disease provide helpful guidance
      for the clinician.

PMID- 9146982
TI  - Genetic susceptibility and the role of hypertension in diabetic nephropathy.
AB  - Evidence exists to suggest that some individuals with diabetes have a genetic
      predisposition to diabetic nephropathy. Cases of nephropathy cluster in families
      and a parental history of hypertension, cardiovascular disease and diabetes is
      more common in patients with diabetic nephropathy. Current evidence favours a
      role for hypertension in the genetic susceptibility to diabetic nephropathy. This
      review focuses on the recent evidence for genetic susceptibility, the role and
      mechanisms of hypertension in the predisposition to nephropathy and the potential
      of a novel sib-pair approach to identify susceptibility genes.

PMID- 9146983
TI  - Genetic renal mechanisms of hypertension.
AB  - An update on renal genetic mechanisms of spontaneous hypertension in rats and in
      human essential hypertension is presented. The findings are discussed,
      highlighting the search of a possible link between the discovered genetic
      abnormality and the renal function changes that may determine the disease. The
      analogies (and/or differences) between the numerous positive findings obtained in
      animal models and the relatively scarce ones obtained in humans are discussed.

PMID- 9146984
TI  - Genetic approach to diagnostic and therapeutic decisions in human hypertension.
AB  - In the most exciting genetic advances in the diagnosis of essential hypertension,
      genes responsible for three distinct forms of low-renin hypertension have been
      identified. Two of these forms are dominant: glucocorticoid remediable
      hypertension (a new gene created by the fusion of the 11 beta-hydroxylase and
      aldosterone synthase genes) and Liddle's syndrome (a defect in the epithelial
      sodium channel). One of the forms is recessive: the syndrome of apparent
      mineralocorticoid excess (a defect in renal 11 beta-hydroxysteroid
      dehydrogenase). The role of more than 20 other genes in causing hypertension has
      been assessed with variable findings. The most convincing evidence supports a
      role for the angiotensinogen gene, where linkage has been documented and an
      association with an intermediate phenotype of hypertension (nonmodulation) has
      been reported.

PMID- 9146985
TI  - Clinical nephrology.

PMID- 9146986
TI  - Pathophysiology of hypertension.

PMID- 9146987
TI  - The explosion of neurogenetics.

PMID- 9146988
TI  - Magnetic resonance and functional magnetic resonance imaging: tools for the study
      of human epilepsy.
AB  - The development of new magnetic resonance imaging base neuroimaging techniques is
      increasing the utility and the importance of magnetic resonance imaging in the
      investigation of patients with epilepsy. Recent advances in magnetic resonance
      imaging, magnetic resonance spectroscopy and functional magnetic resonance
      imaging are not only providing relevant clinical information regarding human
      epilepsy but are also revealing important insights into its basic mechanisms. In
      the present review the role of these new technologies is discussed in the context
      of their clinical utility.

PMID- 9146989
TI  - Mechanisms underlying neuronal migration disorders and epilepsy.
AB  - Neuronal migration disorders are often associated with intractable epilepsy.
      These cortical malformations are quite heterogeneous, suggesting that they may
      result from interference with a diverse set of processes during corticogenesis.
      Progress toward understanding the pathophysiologic basis of these disorders is
      coming from research into the basic mechanisms of corticogenesis, animal models
      of cortical malformations, and molecular genetic approaches to migration
      disorders.

PMID- 9146990
TI  - New nuclear magnetic resonance data in epilepsy.
AB  - Nuclear magnetic resonance methods as a whole have contributed as much to the
      study and treatment of epilepsy as to any branch of medicine. The pace of the
      progress in this field increases as recently developed nuclear magnetic resonance
      techniques mature into practical tools for epilepsy research and management.
      Recent examples of such progress include new data on seizure-related brain water
      diffusion changes, brain metabolic abnormalities in epileptic patients, and
      pharmacologic manipulation of brain gamma-aminobutyric acid.

PMID- 9146991
TI  - Mossy fiber reorganization in the epileptic hippocampus.
AB  - Reorganization of dentate granule cell axons (mossy fibers) is a prominent aspect
      of the pathological changes observed in human temporal lobe epilepsy. Although
      recent work has begun to address the significance of mossy fiber reorganization,
      the specific and overall functional consequences of these network changes remain
      poorly understood. New studies are beginning to provide insight into molecular
      mechanisms underlying this process. Advances in our understanding of the causes
      and effects of mossy fiber reorganization are likely to provide insight into the
      pathophysiology of temporal lobe epilepsy, as well as the larger issue of network
      remodeling following nervous system injury.

PMID- 9146992
TI  - Genetics of human partial epilepsy.
AB  - A minor genetic predisposition to partial epilepsy has been long recognized.
      Recently, a group of idiopathic partial epilepsies with autosomal dominant
      inheritance has been identified. The clinical features and molecular genetic
      findings in these epilepsies are outlined in the present review. The first
      genetic defect in an idiopathic epilepsy has been found in autosomal dominant
      nocturnal frontal lobe epilepsy, the archetype of this newly recognized group of
      inherited partial epilepsies.

PMID- 9146993
TI  - Neurocutaneous syndromes: neurofibromatosis 1, neurofibromatosis 2, and tuberous
      sclerosis.
AB  - Neurofibromatosis 1, neurofibromatosis 2, and tuberous sclerosis are a set of
      dominantly transmitted disorders that have in common the tendency towards
      formation of tumors of the nervous system and other tissues. The genes for
      neurofibromatosis 1, neurofibromatosis 2, and one of two forms of tuberous
      sclerosis have been identified and appear to act as tumor suppressor genes.
      Information is accumulating about pathogenesis that may eventually improve our
      ability to diagnose and treat these disorders.

PMID- 9146994
TI  - Contemporary issues in the management of childhood brain tumors.
AB  - The incidence of childhood brain tumors appears to be on the rise caused in part
      by improvements in neuroimaging and its increased availability. Current protocols
      for treatment of childhood brain tumors are utilizing chemotherapy more
      extensively in addition to and in lieu of radiotherapy to improve survival for
      tumors such as medulloblastoma and high grade astrocytoma, and to lessen
      treatment related morbidity in infants with malignant brain tumors and in older
      children with standard risk medulloblastomas and germ cell tumors. The increasing
      understanding of the molecular events that lead to oncogenesis will help unravel
      the causes and improve therapy for a group of illnesses that cause significant
      neurologic morbidity and mortality.

PMID- 9146995
TI  - Fragile X syndrome.
AB  - The fragile X syndrome is characterized by mental handicap, facial dysmorphism
      and expression of a fragile site at Xq27.3. An expansion of a CGG repeat in the
      5' end of the fragile X mental retardation 1 (FMR1) gene results in the absence
      of the encoded fragile X mental retardation protein, known to play an important
      role in RNA processing and probably the developmental maturation of brain
      neurons.

PMID- 9146996
TI  - Down syndrome.
AB  - Down syndrome, trisomy of chromosome 21, is well investigated because it is a
      genetic disease with characteristic mental retardation and precocious dementia of
      Alzheimer type. Maternal serum markers of human chorionic gonadotrophin
      unconjugated estriol and amyloid precursor protein, nuchal skinfold on ultrasound
      and new genetic probes are developed to allow better detection of Down syndrome.
      The overproduction of A beta 42 because of excessive genes is thought to be a
      leading factor for early onset of dementia in Down syndrome adults. Animal models
      and transgenic mice may be helpful in determining the specific gene and
      pathogenesis for mental retardation and precocious dementia.

PMID- 9146997
TI  - Tourette syndrome.
AB  - This survey of recent literature addressing Tourette syndrome reflects clinical
      and laboratory findings of investigations of behavioral, neuropsychological,
      imaging, genetic, neurobiological and treatment considerations. Tourette syndrome
      is a prototypic neuropsychiatric disorder manifesting a full range of objectively
      describable phenomena from different scientific vantage points and serves as a
      model for study and integrative understanding of brain and behavior.

PMID- 9146998
TI  - Disorders of mitochondria and related metabolism.
AB  - Mitochondrial disorders are caused by mutations in either nuclear or
      mitochondrial genes involved in the synthesis of respiratory chain subunits or in
      their post-translational control. Molecular lesions of mitochondrial DNA are a
      frequent cause of defective oxidative phosphorylation. Although only one mutation
      of nuclear-encoded oxidative phosphorylation subunits has so far been reported in
      humans, numerous biochemically defined disorders are attributed to nuclear gene
      defects. The pathogenesis of these disorders has been investigated through a
      combination of different expertises, including keen clinical observation,
      classical biochemistry and muscle morphology, molecular and cellular biology,
      linkage analysis and population genetic studies.

PMID- 9147000
TI  - Seizure disorders.

PMID- 9147001
TI  - Developmental disorders.

PMID- 9146999
TI  - Muscular dystrophies and the dystrophin-glycoprotein complex.
AB  - Efforts to understand the function of dystrophin, the protein product for the
      Duchenne muscular dystrophy gene, resulted in the purification of the dystrophin
      glycoprotein complex. Over the past year several novel components of this complex
      have been identified. Recent studies have extended the number of muscular
      dystrophies associated with the oligomeric complex to six genetically distinct
      diseases, including three new forms of limb-girdle muscular dystrophy and one
      form of congenital muscular dystrophy.

PMID- 9147002
TI  - Generalized epilepsies: emerging insights into cellular and genetic mechanisms.
AB  - In the past year we have gained significant insights into the molecular and
      genetic mechanisms underlying generalized absence seizures, primarily through the
      study of animal models. Also a new understanding has emerged about the genetic
      bases of certain syndromes in which generalized myoclonic and tonic-clonic
      seizures are expressed. New insights into these different types of generalized
      seizures may lead eventually to new therapies.

PMID- 9147003
TI  - Mechanisms of action of new antiepileptic drugs.
AB  - Many new antiepileptic drugs have been developed to treat seizure disorders. The
      established antiepileptic drugs reduce neuronal excitability by promoting sodium
      channel inactivation, inhibiting T-type calcium channels, or enhancing gamma
      aminobutyric acid type A receptor-mediated inhibition. Several of the newer
      agents employ similar mechanisms, whereas others may enhance gamma-aminobutyric
      acid-ergic inhibitory systems or inhibit glutamatergic excitatory
      neurotransmission, and may be neuroprotective or antiepileptogenic.

PMID- 9147004
TI  - Linking molecular biology to clinical advances in developmental neurology.

PMID- 9147005
TI  - Rejection criteria for endotracheal aspirates in neonates. Clinical impact.
AB  - It has been suggested that endotracheal suction specimens from adult and
      pediatric patients be rejected for culture if no organisms are seen on Gram's
      stain. We reviewed the experience in neonates under three months of age from our
      neonatal intensive care unit. Of 195 such endotracheal specimens, 86 (44%) had no
      growth by culture, 83 (43%) grew normal flora only, and 26 (13%) from 22 patients
      grew a potential pathogen. Detailed chart review was undertaken to determine what
      the clinical outcome would have been if the culture information were not provided
      for these patients. Based on this analysis, almost all patients with Gram
      negative rods would have empirically received antibiotics on clinical grounds
      regardless of culture results, and at least one received antibiotics
      unnecessarily based on a culture result. On the other hand, two patients whose
      cultures grew Trichosporon and Aspergillus would have been missed.

PMID- 9147006
TI  - Variations in DNA subtype and antifungal susceptibility among clinical isolates
      of Candida tropicalis.
AB  - Candida tropicalis has been known to be a major cause of invasive Candida
      infection. Numerous reports have documented C. tropicalis as the most common
      species of Candida other than C. albicans. The epidemiology and antifungal
      susceptibility of C. tropicalis are poorly defined. A series of 89 clinical
      isolates of C. tropicalis from 56 patients hospitalized at seven different U.S.
      medical centers were analyzed by restriction endonuclease analysis of genomic DNA
      (REAG) using the restriction enzymes Sfil and BssHII followed by pulsed-field gel
      electrophoresis (PFGE). The MICs of the isolates for amphotericin B, 5
      fluorocytosine (5FC), fluconazole, itraconazole, and D0870 were determined by
      microbroth dilution testing. A total of 49 different DNA types were identified
      among the 89 isolates. Generally, each DNA type represented an individual
      patient, and serial isolates from the same patient were the same DNA type. Small
      clusters of patients infected with the same DNA type of C. tropicalis suggested
      possible nosocomial transmission. The MICs of the various antifungal agents were
      amphotericin B 0.5 to 2.0 micrograms/ml (MIC90 = 2.0 micrograms/ml), 5FC 0.25 to
      1.0 microgram/ml (MIC90 = 0.5 microgram/ml), fluconazole 0.25 to 8.0
      micrograms/ml (MIC90 = 1.0 microgram/ml), itraconazole 0.03 to 1.0 microgram/ml
      (MIC90 = 0.5 microgram/ml), and D0870 0.007 to 0.12 microgram/ml (MIC90 = 0.03
      microgram/ml). These data support previous observations that infections caused by
      C. tropicalis frequently originate from the patient's own endogenous flora.
      Clusters of a single strain in individual hospitals also suggests that limited
      nosocomial transmission may occur.

PMID- 9147007
TI  - Serological diagnosis of hepatitis C virus in patients with liver disease in
      Saudi Arabia. Evaluation of antibody determination by recombinant immunoblot
      assays in relation to RNA detection by polymerase chain reaction.
AB  - Sera from 164 Saudi Arabian patients with non-A, non-B hepatitis liver disease
      were examined for antibodies to hepatitis C virus (HCV) by second- and third
      generation recombinant immunoblot assay (RIBA-2 and RIBA-3) and for HCV RNA by
      polymerase chain reaction (PCR). By using RIBA-2, 92 (56.1%) were reactive, 64
      (39%) were nonreactive, and 8 (4.9%) were indeterminate. By using RIBA-3, 98
      (59.7%) were reactive 60 (36.6%) were nonreactive, and 6 (3.7%) were
      indeterminate. By using PCR, 108 (65.9%) were positive. Of the eight RIBA-2
      indeterminate samples, seven became RIBA-3 reactive but PCR-positive, and one
      became RIBA-3 nonreactive but PCR-negative. Of the six RIBA-3 indeterminate
      samples, five were RIBA-2 nonreactive but PCR-positive, and one was RIBA-2
      reactive but PCR-negative. From our study on Saudi patients, we conclude that
      RIBA-3 has slightly but not significantly improved the results of anti-HCV
      antibody detection, and is probably of more value to resolve those indeterminate
      samples by RIBA-2. Although expensive, PCR remains the most reliable HCV
      diagnostic method until an HCV antigen detection test is available.

PMID- 9147008
TI  - A 1994-95 survey of Haemophilus influenzae susceptibility to ten orally
      administered agents. A 187 clinical laboratory center sample in the United
      States.
AB  - During August, 1994 to April, 1995, a total of 2278 clinical isolates of
      Haemophilus influenzae were obtained from 187 clinical laboratories in the United
      States (U.S.). The vast majority of these isolates (75%) were from respiratory
      sites, and the remaining organisms were from blood, ear, eye, and spinal fluid
      sources. The overall rate of beta-lactamase production and ampicillin resistance
      was 36%. The antimicrobial susceptibility of isolates was determined by reference
      broth microdilution testing against ten orally administered agents. MIC values
      were compared according to 12 geographical regions, inpatient or outpatient
      status, gender, and eight age groupings. Modest and occasionally significant
      differences were observed: 1) greater numbers of beta-lactamase-producing strains
      among outpatients, in males, in the mid-Atlantic region, and in children < or =
      12 years of age; 2) lower prevalence of beta-lactamase-producing isolates in the
      Southeast and Pacific regions; 3) cefaclor, cefprozil, and loracarbef activity
      was lowest among the younger children (< or = six years); and 4) macrolide in
      vitro efficacy was lowest in patients > 50 years of age and in three eastern
      regions. Overall, more than 99% of the strains were susceptible to
      amoxicillin/clavulanic acid, cefixime, and cefpodoxime (e.g., widest potential
      clinical use). Susceptibilities using National Committee for Clinical Laboratory
      Standards (NCCLS) breakpoint criteria for the other agents were: 96.6% to
      cefuroxime, 86.5% to loracarbef, 84.0% to clarithromycin, 81.8% to cefaclor, and
      80.7% to cefprozil. Non-beta-lactamase mechanisms of resistance to ampicillin
      were rare (0.2%) or episodic and were attributed to altered penicillin-binding
      proteins. Although there is an increased prevalence of beta-lactamase production
      among H. influenzae isolates compared to prior years, four beta-lactams remain
      highly active (> 95% susceptibility) against contemporary strains of H.
      influenzae. Other monitored compounds seem to have declined in spectrum and
      surveillance trials for resistance among H. influenzae isolates should continue
      in an effort to identify trends in the U.S.

PMID- 9147009
TI  - Assessment of the synergistic interactions of levofloxacin and ampicillin against
      Enterococcus faecium by the checkerboard agar dilution and time-kill methods.
AB  - Multidrug-resistant enterococci have become increasingly difficult to eradicate
      in a growing number of nosocomial infections. With the emergence of vancomycin
      resistant enterococci, the use of synergistic antibiotic combinations has become
      one of the only remaining therapeutic options. Levofloxacin, the active l-isomer
      of ofloxacin, is a new oral and intravenous fluoroquinolone with a broad spectrum
      of activity against numerous Gram-positive, Gram-negative, and atypical
      organisms. The in vitro activity of levofloxacin, alone and in combination with
      ampicillin, against recent clinical isolates of Enterococcus faecium was assessed
      for synergistic interactions using the checkerboard agar dilution technique and
      time-kill methodology. Against all strains, the static technique of checkerboard
      agar dilution demonstrated indifferent or additive effects for the ampicillin +
      levofloxacin combination. With the dynamic time-kill technique, synergy was
      demonstrated for ampicillin (16 micrograms/ml) + levofloxacin (2 micrograms/ml)
      combination against three levofloxacin-sensitive, ampicillin-resistant isolates.
      At 24 h, the combination yielded a > or = 2-log10 decrease in CFU/ml compared to
      levofloxacin alone, while ampicillin had negligible effects. Against both a
      levofloxacin-intermediate, ampicillin-resistant isolate, and a highly
      levofloxacin-resistant, ampicillin-resistant isolate, none of the
      ampicillin+levofloxacin combinations tested demonstrated a synergistic
      interaction. The time-kill method suggested synergy for the
      ampicillin+levofloxacin combination against some strains of E. faecium.

PMID- 9147010
TI  - Comparative evaluation of etest for susceptibility testing Neisseria meningitidis
      with eight antimicrobial agents. An investigation using U.S. Food and Drug
      Administration regulatory criteria.
AB  - Invasive infections caused by Neisseria meningitidis continue to be a serious
      clinical problem for therapy, epidemiology, and potential prophylaxis. Multiple
      antimicrobial resistances have emerged among meningococcal strains including
      elevated MICs to penicillin, sulfonamides, tetracyclines, and rifampin. Thus, the
      need to perform accurate susceptibility testing of meningococci in clinical
      practice and for surveillance programs has renewed priority. In this study, for
      the first time Etest (AB Biodisk, Solna, Sweden) was compared to a reference agar
      dilution method using a large number (100) of clinical strains selected for a
      range of drug resistances. Etest quantitative accuracy (+/-one log2 dilution
      agreement) ranged from 94% (penicillin) to 100% (three drugs) for the eight
      clinically useful antimicrobial agents tested. Intermethod categorical accuracy
      for all drug ranged from 92% (penicillin, erythromycin) to 100% (five drugs),
      without false-susceptible or -resistant errors using Etest. Etest and reference
      methods were highly reproducible (99.6 to 100.0%, respectively). Quantitative
      discords between methods (> or = two log2 dilutions) were not reproducible and
      resolved following repeated testing. Etest method proved to be an accurate and
      reproducible quantitative method for testing N. meningitidis strains for the
      compared antimicrobial agents (eight) often utilized for therapy and prophylaxis
      of serious meningococcal disease.

PMID- 9147011
TI  - Use of ceftizoxime screening for the detection of cephalosporin-resistant
      pneumococci.
AB  - Two hundred and ten pneumococcal isolates underwent ceftizoxime disk (30
      micrograms) screening to predict cephalosporin resistance. Forty-six isolates
      failed screening with 36 (78%) demonstrating intermediate/resistant MICs.
      Sensitivity and specificity were 100 and 95%, respectively. The ceftizoxime disk
      screen is an effective method of identifying potentially cephalosporin-resistant
      isolates.

PMID- 9147012
TI  - Reductive activation of nitroheterocyclic compounds.
AB  - 1. Nitroaromatic compounds are important chemotherapy agents. 2. Their selective
      toxicity is determined by reduction to the biologically active form in the
      absence of oxygen. 3. Nitroaromatics are extensively used in the treatment of
      anaerobic infections and to target hypoxic tumor cells in cancer therapy. 4.
      Possible mutagenic action is related to the relative ease of nitro group
      reduction. 5. The mode of action and clinical application of nitroaromatic
      compounds is summarized.

PMID- 9147013
TI  - Superoxide anions, free-radical scavengers, and nitrergic neurotransmission.
AB  - 1. There is now strong evidence that the L-arginine/nitric oxide (NO) pathway
      generates the transmitter released from certain nonadrenergic, noncholinergic
      nerves that mediate smooth-muscle relaxation in the respiratory,
      gastrointestinal, and urogenital tracts. In particular, nitric oxide synthase
      (NOS) has been detected in these nitrergic nerves, and nerve-induced relaxation
      can be prevented by NOS inhibitors. Thus, free-radical NO has been considered the
      putative transmitter candidate. 2. Despite such evidence, a number of superoxide
      anion-generating compounds and direct NO scavengers have been found to abolish
      relaxations to exogenous NO, but to have very little effect on relaxations in
      response to nitrergic field stimulation. A number of hypotheses have been put
      forward to explain this paradox: first, that the NO generated within the nerve is
      attached to a carrier molecule (such as a thiol) to form an adduct, that is
      released into the junctional gap and that is resistant to superoxide anions and
      other scavengers; second, that over short distances (up to 200 microns) the rapid
      diffusion characteristics of NO render it resistant to inhibition by scavengers;
      third, that NO is indeed released as a free radical, but that it is protected
      from radical scavengers by other substances present in the junctional region. 3.
      Recent experimental evidence supports the third explanation, because nitrergic
      relaxations, normally resistant to inhibition by superoxide anions, become
      sensitive following inactivation of copper/ zinc superoxide dismutase (Cu/Zn
      SOD); the inhibition can be reversed by adding exogenous Cu/Zn SOD (or
      ascorbate). In addition, the ability of two NO-scavenger compounds, hydroquinone
      and carboxy-PTIO, to inhibit relaxations to exogenous NO is prevented by certain
      physiological antioxidants (ascorbate and reduced glutathione in the case of
      hydroquinone, and ascorbate and alpha-tocopherol in the case of carboxy-PTIO). 4.
      Thus, it is possible that the presence of integrated antioxidant mechanisms
      within the tissue protects neuronally- released NO from attack by scavenging
      molecules; exogenous NO would be vulnerable before reaching the protection of the
      tissue, thus explaining the paradoxical effects mentioned. Organ antioxidant
      status may therefore be very important in preserving the potency of nitrergic
      transmission and in preventing NO from reacting with other compounds to produce
      cytotoxic metabolites (eg., with superoxide anions to form peroxynitrite).

PMID- 9147014
TI  - Is the mitochondrial benzodiazepine receptor involved in the control of airway
      smooth muscle tone?
AB  - 1. In addition to binding to GABAA receptors in the central nervous system,
      benzodiazepines have also been reported to recognize high affinity binding sites
      in several different peripheral tissues. 2. These peripheral benzodiazepine
      receptors likely consist of distinct integral membrane proteins, which are
      predominantly localized in the outer mitochondrial membrane and may be associated
      to form a heteropolymeric receptor complex. One such protein, identified for its
      ability to bind a class of benzodiazepines and isoquinolines, has been purified
      and the corresponding complementary DNA (cDNA) has been cloned and characterized.
      Furthermore, the structure of the rat gene encoding this protein has been
      clarified, thus potentially opening new insights into the molecular mechanisms
      responsible for receptor regulation. 3. Although the exact physiologic and/or
      pharmacologic role of peripheral benzodiazepine receptors is still unknown, their
      wide tissue distribution suggests an involvement in many cellular phenomena. 4.
      In particular, several lines of investigation indicate that these receptors,
      densely expressed on airway smooth muscle of various species, may contribute to
      the modulation of bronchomotor tone and perhaps to the pathogenesis of asthma and
      airway hyperresponsiveness.

PMID- 9147015
TI  - Remacemide hydrochloride: a novel antiepileptic agent.
AB  - 1. Remacemide hydrochloride has been shown to possess anticonvulsant activity in
      a wide range of animal models of epilepsy with ED50s in the 6-60 mg/kg range,
      depending on the species and route of administration. The compound also has been
      shown to be effective clinically as add-on therapy for partial seizures. 2.
      Degradation of remacemide yields the desglycinated metabolite that is
      approximately 2-fold more potent as an anticonvulsant agent than the parent drug.
      3. Both compounds displace [3H]MK801 binding from the cerebral cortical
      membranes, and the metabolite is approximately 150-fold more potent in doing so
      than remacemide. This effect, together with the findings that the desglycinate
      reduces N-methyl-D-aspartate (NMDA)-induced depolarizations in a variety of
      preparations, suggests that the mechanism of action is through blockade of the
      channel site of the NMDA-receptor complex. 4. Remacemide and its metabolite, in
      common with other antiepileptic agents, block sustained repetitive-firing in
      cultured neurons. The metabolite also has been shown to decrease glutamate
      release from cortical slices. 5. Remacemide hydrochloride has neuroprotective
      properties when tested on models of cerebral ischemia. 6. The drug has low
      toxicity in contrast to other NMDA-channel-blocking compounds, such as MK801 and
      phencyclidine, probably because of its low affinity for the channel-binding site.

PMID- 9147016
TI  - Mechanics of manganese ions-induced contraction of ileal longitudinal muscle in
      Ca(2+)-free, high-K+ medium.
AB  - 1. Mn2+ (5 mM) evoked the contraction of ileal longitudinal muscle in a Ca(2+)
      free, high-K+ (60 mM) medium. Metabolic inhibitors, such as iodoacetic acid or
      glucose removal, reduced the contraction by Mn2+ in the Ca(2+)-free, high-K+
      medium, suggesting that the contraction by Mn2+ depends on energy metabolism. 2.
      By the abrupt decrease in length of the ileum during contraction 3 hr after the
      addition of 5 mM Mn2+ in Ca(2+)-free, high-K+ medium, a rapid decrease in tension
      was seen, and redevelopment of tension followed, which is indicative of an active
      state. 3. In the late phase, 5 hr after the Mn(2+)-induced contraction, a similar
      decrease in the length also caused a rapid decrease in tension, without however,
      a redevelopment of tension. This probably indicates that the myofilaments in this
      phase transferred to a state of static interaction.

PMID- 9147017
TI  - Effects of fluoxetine hydrochloride and fluvoxamine maleate on different
      preparations of isolated guinea pig and rat organ tissues.
AB  - 1. Fluoxetine and fluvoxamine reinforced the response to norepinephrine of
      isolated rat vas deferens incubated in Krebs-Henseleit solution. 2. This
      reinforcement disappeared when cocaine, 17 beta-estradiol, and propranolol were
      added to the incubation medium. 3. Fluoxetine and fluvoxamine did not have
      antimuscarinic effect, but they did have antihistaminic effect, and at high
      concentrations they inhibited the contraction induced by potassium ion on the
      isolated rat uterus preparation (IC50 3.99 x 10(-6) and 1.82 x 10(-5) M,
      respectively).

PMID- 9147018
TI  - Nitric oxide, prostaglandin, and sensory neurons in gastric mucosal blood flow
      response during acid secretion in rats.
AB  - 1. The mechanism underlying the increase of gastric mucosal blood flow (GMBF)
      during acid secretion induced by pentagastrin was investigated in anesthetized
      rats, in relation to nitric oxide (NO), prostaglandin (PG), and sensory neurons.
      2. An intravenous infusion of pentagastrin at 60 micrograms/kg/h (submaximal
      dose) produced an increase of acid secretion and GMBF as determined by laser
      Doppler flowmetry, and the GMBF response was totally attenuated when the acid
      secretion was inhibited by omeprazole or when the luminal H+ was removed by
      mucosal perfusion with glycine (200 mM). 3. Prior administration of NG-nitro-L
      arginine methyl ester (L-NAME, 5 mg/kg, IV), a NO synthase inhibitor,
      significantly mitigated the GMBF response to pentagastrin, without any influence
      on acid secretion, and this effect was antagonized by coadministration of L
      arginine (500 mg/kg IP). 4. The increase of GMBF during pentagastrin infusion
      also was significantly mitigated by indomethyacin (5 mg/kg, SC) or sensory
      deafferentation following capsaicin pretreatment, had no effect on the acid
      secretion, and was totally inhibited by the combined treatments with indomethacin
      plus L-NAME in addition to sensory deafferentation. 5. Pentagastrin infusion for
      8 hr did not by itself cause any macroscopic damage in the stomach, but
      additional treatments with L-NAME, and indomethacin plus sensory deafferentation
      provoked severe lesions in the gastric mucosa. 6. These results suggest that the
      increase of GMBF induced by submaximal dose of pentagastrin totally depends on
      luminal H+. This process seems to be mediated by endogenous NO and PGs, as well
      as capsaicin-sensitive sensory neurons, and to play a pivotal role in maintaining
      mucosal integrity during acid secretion.

PMID- 9147019
TI  - Effect of alpha 1-adrenoceptor antagonists on urinary bladder function in
      urethane-anesthetized rats.
AB  - 1. We investigated the effects of selective alpha 1-adrenoceptor antagonists on
      rhythmic bladder contraction and cystometrograms as representative of urinary
      bladder function in urethane-anesthetized rats. 2. The selective alpha 1
      adrenoceptor antagonists tamsulosin (0.03-3 micrograms/kg IV), prazosin (0.03-3
      micrograms/ kg IV) and bunazosin (0.03-3 micrograms/kg IV) exerted little effect
      on the amplitude and frequency of rhythmic bladder contraction in anesthetized
      rats. In contrast, the antipollakiuria agent flavoxate (5 and 10 mg/kg IV)
      induced a dose-dependent disappearance in frequency without affecting the
      amplitude of the contractions. 3. Tamsulosin (1 and 3 micrograms/kg IV), prazosin
      (1 and 3 micrograms/kg IV), and bunazosin (1 and 3 micrograms/kg IV) exerted no
      effect on the cystometrogram, either. However, flavoxate (5 and 10 mg/kg IV)
      raised the micturition threshold pressure and prolonged the time to micturition.
      4. These results suggest that the alpha 1-adrenoceptor plays little role in
      urinary bladder contraction in anesthetized rats.

PMID- 9147020
TI  - Microsomal and peroxisomal fatty acid oxidation in bile duct ligated rats: a
      comparative study between liver and kidney.
AB  - 1. Microsomal cytochrome P-450 and peroxisomal fatty acid oxidation was studied
      in the kidney of rats 7 days after bile duct ligation (BDL) and a comparative
      study between kidney and liver was done. 2. Only in the liver did cholestasis
      decrease the cytocrome P-450 content and the peroxisomal fatty acid beta
      oxidation, the catalase activity, and the microsomal metabolism of lauric acid
      and aminopyrine. 3. In contrast, cholestasis did not influence these activities
      in the kidney. The microsomal and peroxisomal activities studied responded in a
      coordinate way to cholestasis. 4. These results could suggest the possibility of
      a cause-and-effect relationship between microsomal cytochrome P-450 and
      peroxisomal activity.

PMID- 9147021
TI  - Effects of enalapril in rats with pressure overload cardiac hypertrophy.
AB  - 1. The effects of the ACE inhibitor enalapril were studied in rats with cardiac
      hypertrophy induced by abdominal aortic constriction. This experimental model has
      shown that pump failure can be evidenced only during increased workload. 2. Under
      basal conditions, enalapril at 1-3 mg/kg induced a significant reduction in blood
      pressure. During the acute volume loading or the increase in afterload due to a
      total aortic occlusion, only rats treated with 3 mg/kg enalapril, but not 1
      mg/kg, received a hemodynamic benefit that was paralleled by a significant
      reduction in cardiac hypertrophy. 3. The present study demonstrates that
      reduction in blood pressure on its own was not sufficient to improve cardiac
      function. A decrease in blood pressure accompanied with hypetrophy regression
      were necessary to normalize hemodynamic parameters in pressure-overloaded rats.

PMID- 9147022
TI  - Metabolism of phenylethanolamines and 2-oxo-2-phenylethylamines in the rat.
AB  - 1. The metabolism of a series of phenylethanolamines and 2-oxo-2
      phenylethylamines was examined in vivo in the rat. 2. The urinary excretion of
      the corresponding mandelic acids was, in general, considerably greater for 2-oxo
      2-phenylethylamines than for the corresponding phenylethanolamines. Of the
      putative metabolites of the former class of compounds only phenylglyoxals yielded
      mandelic acids.

PMID- 9147023
TI  - Cardiac and hemodynamic effects of TZC-5665, a novel pyridazinone derivative, and
      its metabolite in humans and dogs.
AB  - 1. TZC-5665 is a novel pyridazinone derivative with vasodilatory and beta
      adrenergic blocking activities and type III phosphodiesterase inhibitory action.
      2. In healthy volunteers, TZC-5665 was rapidly absorbed and immediately
      metabolized. Its main metabolite, M-2, remained at a higher concentration in
      plasma. Orally administered TZC-5665 reduced end-diastolic left ventricular
      volume (20.16 ml) and exhibited a tendency to increase ejection fraction (0.04).
      3. In dogs, M-2 dose-dependently increased cardiac contractility and reduced both
      preload and afterload. These effects appeared more potent in the failed heart
      than in the normal heart. At the same dose (30 micrograms/kg), the effects of M-2
      seem to be more potent than those of milrinone. 4. We concluded that TZC-5665 is
      a useful medication for treating patients with chronic congestive heart failure
      (CHF) because of the positive inotropic and vasodilating effects due to its
      active metabolite in addition to its own beta-adrenergic blocking actions.

PMID- 9147024
TI  - Picolinic acid and indole-2-carboxylic acid: two types of glycinergic compounds
      modulate motor function differentially.
AB  - 1. A putative agonist for the strychnine-sensitive glycine receptor picolinic
      acid was tested for its anticonvulsant activities in mice and muscle-relaxant
      activities in rats and compared with indole-2-carboxylic acid (I2CA), an
      antagonist for the strychnine-insensitive glycine receptor. Their effects on
      segmental reflexes in the cat spinal cord were examined to elucidate their sites
      of action. 2. Picolinic acid (200 and 400 mg/kg IP) delayed the onsets of
      strychnine- but not pentylenetetrazole-induced seizures. It delayed the onsets of
      bicuculline-induced seizures only at the higher dose. I2CA (200 and 400 mg/kg IP)
      delayed the onsets of these 3 kinds of seizures. Both compounds reduced muscle
      tone in rat decerebrate rigidity at a dose of 100 mg/kg IV. 3. Picolinate
      methylester, a picolinate derivative with higher lipophilicity, depressed spinal
      reflexes in both intact and spinalized cats at cumulative doses of 25 to 200
      mg/kg IV. I2CA (50 mg/kg IV) inhibited spinal reflexes only in intact
      preparations. 4. These results suggest that the anticonvulsant and muscle
      relaxant activities of picolinic acid (PA) are due to inhibition of spinal
      neurons, but that I2CA selectively affects supraspinal structures.

PMID- 9147025
TI  - Transcriptional mechanisms involved in the relaxant effect of zeranol on isolated
      rat uterus.
AB  - 1. The effect of zeranol (3-100 microM) on rat uterus contractions induced by KCl
      (60 mM) and CaCl2 (30 microM-10 mM) has been assayed. 2. Zeranol relaxed the
      tonic contraction induced by KCl in a concentration-dependent manner (IC50 15.62
      +/- 2.66 microM). CaCl2 (0.1-10 mM) did not counteract the relaxing effect of
      zeranol. 3. CaCl2 (30 microM -10 mM) produced a concentration-dependent
      contraction of rauuterus in medium lacking calcium plus KCl (60 mM) (EC50 0.34 +/
      0.03 mM). Zeranol (8 microM) displaced the CaCl2 concentration-response curve to
      the right and increased the EC50 to 1.27 +/- 0.57 mM (P < 0.05) without modifying
      the Emax. 4. The antiestrogen tamoxifen (1 microM) and the inhibitor of cAMP
      dependent protein kinase TPCK (3 microM) did not modify the effect of zeranol.
      However, the inhibitors of transcription (actinomycin D, 4 microM), protein
      synthesis (cycloheximide, 100 microM), and ornithine-decarboxilase (alpha
      difluoromethyl-ornithine, 10 mM)) antagonized the effect of zeranol, increasing
      the IC50 to 50.2 +/- 6.2 microM, 122 +/- 6.9 microM, and 23.51 +/- 1.14 microM,
      respectively. 5. Our results suggest that the relaxing effect of zeranol on rat
      uterus smooth muscle is produced by mechanisms unrelated to cAMP and estrogen
      receptors, but involves transcriptional effects and polyamine synthesis.

PMID- 9147026
TI  - Mipafox differential inhibition assay for heart muscle cholinesterases: substrate
      specificity and inhibition of three isoenzymes by physostigmine and quinidine.
AB  - 1. A differential inhibition assay was developed for the quantitative
      determination of cholinesterase isoenzymes acetylcholinesterase (AChE; EC
      3.1.1.7), cholinesterase (BChE; EC 3.1.1.8), and atypical cholinesterase in small
      samples of left ventricular porcine heart muscle. 2. The assay is based on
      kinetic analysis of irreversible cholinesterase inhibition by the
      organophosphorus compound N,N'-di-isopropylphosphorodiamidic fluoride (mipafox).
      With acetylthiocholine (ASCh) as substrate (1.25 mM), hydrolytic activities (A)
      of cholinesterase isoenzymes were determined after preincubation (60 min, 25
      degrees C) of heart muscle samples with either saline (total activity, A tau), 7
      microM mipafox (AM1), or 0.8 mM mipafox (AM2): (BChE) = A tau-AM1, (AChE) = AM1
      AM2, (Atypical ChE) = AM2. 3. The mipafox differential inhibition assay was used
      to determine the substrate hydrolysis patterns of myocardial cholinesterases with
      ASCh, acetyl-beta-methylthiocholine (A beta MSCh), propionylthiocholine (PSCh),
      and butyrylthiocholine (BSCh). The substrate specificities of myocardial AChE and
      BChE resemble those of erythrocyte AChE and serum BChE, respectively. Michaelis
      constants KM with ASCh were determined to be 0.15 mM for AChE and 1.4 mM for
      BChE. 4. Atypical cholinesterase, in respect to both substrate specificity and
      inhibition kinetics, differs from cholinesterase activities of vertebrate tissue
      and, up to now, could be identified exclusively in heart muscle. The enzyme's
      Michaelis constant with ASCh was determined to be 4.0 mM. 5. The reversible
      inhibitory effects of physostigmine (eserine) and quinidine on heart muscle
      cholinesterases were investigated using the differential inhibition assay. With
      all three isoenzymes, the inhibition kinetics of both substances were strictly
      competitive. The physostigmine inhibition of AChE was most pronounced (Ki = 0.22
      microM). Quinidine most potently inhibited myocardial BChE (Ki = 35 microM).

PMID- 9147027
TI  - Effect of chronic anesthesia on the drug-metabolizing enzyme system and heme
      pathway regulation.
AB  - 1. The effect of chronic enflurane or isoflurane anesthesia on hepatic heme
      regulation and the drug-metabolizing system in mice treated or not with
      phenobarbital (PB) was investigated. 2. delta-Aminolevulinic acid synthetase was
      induced 50-170% in all cases. Urinary porphyrin precursor excretion was also
      enhanced, but these values were lower when animals also received PB. 3.
      Cytochrome (CYT) P-450 levels were enhanced in animals treated with enflurane
      whether or not they were given PB. 4. Gluthatione-S-transferase activity was
      induced by enflurane (138%) or isoflurane (174%), and even more in animals
      receiving PB also. Sulfatase activity was increased more than 60% with
      anesthetics. Isoflurane produced a 50% increase of beta-glucuronidase activity
      and a 35% diminution of tryptophan pyrrolase. 5. The association between
      anesthetics and PB produced diverse effects on the metabolizing enzyme system. 6.
      Data suggest that both anesthetics, chemically related, could act through two
      different mechanisms, however, with the same final effect: heme pathway
      deregulation.

PMID- 9147028
TI  - Effect of the selective 5-HT receptor agonists 8-OHDPAT and DOI on behavior and
      brain biogenic amines of rats.
AB  - 1. The behavioral responses, as well as the biogenic amines and metabolite
      contents in discrete brain areas were determined in male rats subcutaneously
      treated with a 5-HT1A (8-OHDPAT) or 5-HT2A (DOI) agonist at doses (0.5-2 mg/kg)
      sufficient to produce the typical effects of the stimulation of these brain
      receptor subtypes. 2. Besides the expected effects (i.e., forepaw treading, flat
      body posture and inhibition of 5-HT release and turnover), 8-OHDPAT displayed
      signs of increased dopaminergic transmission. 3. DOI increased dopamine turnover
      and provoked stereotypical behavior, in addition to head shakes and body
      twitches. 4. Moreover, DOI induced both forepaw treading and flat body posture,
      which are believed to be typical responses to the stimulation of brain 5-HT1A
      receptors. 5. This finding cannot be explained on the basis of actual knowledge,
      because the affinity of DOI for 5-HT1A receptor has been found to be very low,
      whereas indirect mechanisms of activation of this receptor subtype triggered by
      stimulation of 5-HT2A receptor are actually unknown.

PMID- 9147029
TI  - Different starting times of alpha-tocopherol and gamma-tocotrienol
      supplementation and tumor marker enzyme activities in the rat chemically induced
      with cancer.
AB  - 1. alpha-Tocopherol (alpha-T) and gamma-tocotrienol (gamma-T) were supplemented
      continuously for 8 weeks in the diets of normal rats and rats chemically induced
      with cancer using diethylnitrosamine (DEN), 2-acetylaminofluorene (AAF) and
      partial hepatectomy. Hepatocarcinogenesis was followed by determining the plasma
      gamma-glutamyl-transpeptidase (GGT) and alkaline phosphatase (ALP) activities as
      well as placental glutathione S-transferase (PGST) and GGT activities
      histochemically, at 4-week intervals. 2. Male Rattus norvegicus were supplemented
      alpha-T and gamma-T at two different doses of 30 and 300 mg/kg diet. The
      supplementation was started at three different times: simultaneously with DEN
      administration; 4 weeks; and 8 weeks after DEN administration. 3. Elevation of
      plasma GGT activities and formation of PGST and GGT positive foci were attenuated
      significantly (P < 0.05) when alpha-T and gamma-T were supplemented
      simultaneously with cancer induction. Supplementation begun 4 and 8 weeks after
      cancer induction did not affect plasma enzyme activities and formation of enzyme
      positive foci. 4. alpha-T was more effective than gamma-T, and a lower dose of 30
      mg/kg was found to be more effective in reducing the severity of
      hepatocarcinogenesis.

PMID- 9147030
TI  - Myonecrosis induced by guanidine in the mouse isolated phrenic nerve diaphragm
      preparation.
AB  - 1. The myonecrosis induced by guanidine in the mouse phrenic nerve diaphragm
      preparation was investigated using both light microscopy and myographic
      recordings. Preparations were incubated with 10 mM guanidine for 60 min in the
      absence and presence of electrical stimulation. At the end of this period, the
      drug was washed out and the nutritive medium replaced with fixative solution to
      prevent morphological artefacts. 2. Guanidine produced a triphasic change in the
      amplitude of twitch tension evoked indirectly through the motor nerve. This
      response consisted of an initial facilitation followed by a neuromuscular
      blockade and a secondary facilitatory effect after removal of the drug. 3.
      Morphological analysis of the muscle showed various structural alterations of the
      fibers, including the presence of very dark swollen cells with or without small
      clear vacuoles, delta lesions with densely or loosely clumped myofibrils,
      irregular clear spaces, indistinct masses of degraded myofibrils, and, in extreme
      cases, "ghost" cells. All of these effects were attributed to the presence of
      high cytosolic calcium concentrations. 4. Pretreatment with tetrodotoxin (TTX,
      3.13 microM) diminished but did not prevent the guanidine-induced morphological
      abnormalities in the muscle cells. This finding suggests that TTX can interfere
      to a certain extent with the influx of guanidine into muscle fibers through
      sodium channels. 5. An attempt was made to correlate the myographic findings with
      the muscle morphological alterations seen after guanidine removal.

PMID- 9147031
TI  - Novel effects of guanidine on the neuromuscular junction.
AB  - 1. The effects of guanidine on the isolated mouse phrenic nerve diaphragm (MPND)
      and chick biventer cervicis (CBC) neuromuscular preparations were determined by
      myographic and electrophysiological methods. 2. Guanidine at concentrations of 5
      10 mM induced an initial facilitation followed by neuromuscular blockade in both
      preparations. In the isolated MPND such blockade was associated with the
      abolition of miniature end-plate potentials (MEPPs), but in the CBC the
      acetylcholine-induced contracture remained unimpaired. After guanidine removal, a
      heretofore undescribed pronounced facilitation of neuromuscular transmission
      associated with an increase in MEPP frequency was observed. Simultaneously, the
      muscular contractions exhibited delayed relaxation and aftercontractions. 3. The
      K+ channel opener, cromakalim (100-200 microM) inhibited both the well-described
      initial and the novel postremoval facilitatory effects of guanidine in a
      concentration-dependent manner. These findings are consistent with the proposal
      that guanidine blocks K+ channels in motor nerve endings. 4. The guanidine
      induced NMB was reverted by increasing the Ca2+ concentration (1.8-5 mM) in the
      nutritive solution. 5. Tetrodotoxin (TTX, 1.56 microM) did not influence the
      increase in MEPPS frequency induced by guanidine (10 mM) but did reduce the rise
      in MEPPS frequency observed after guanidine removal. 6. The present findings
      indicate that the effects of guanidine on the neuromuscular junction are more
      complex than currently described because they include a neuromuscular blockade
      and a post-removal facilitation previously unreported in the literature.

PMID- 9147032
TI  - Effects of spinally and supraspinally injected 3-isobutyl-1-methylxanthine,
      cholera toxin, and pertussis toxin on cold water swimming stress-induced
      antinociception in the mouse.
AB  - 1. The cold (4 degrees C) water swimming stress (CWSS) for 3 min significantly
      increased the inhibition of the tail-flick response in ICR mice. 2. Pertussis
      toxin (PTX, 0.05-0.5 microgram) in mice pretreated intrathecally (IT) for 6 days
      attenuated the inhibition of the tail-flick response induced by CWSS. However,
      intracerebroventricular (ICV) pretreatment with PTX at the same doses did not
      affect CWSS-induced inhibition of the tail-flick inhibition. 3. 3-Isobutyl-1
      methylxanthine (IBMX, 0.01-1 ng) in mice pretreated IT for 10 min dose
      dependently attenuated the inhibition of the tail-flick response induced by CWSS.
      However, IBMX in mice ICV pretreated ICV at the same doses was not effective in
      attenuating the CWSS-induced inhibition of the tail-flick response. 4. Neither IT
      nor ICV pretreatment with cholera toxin (CTX, 0.05-0.5 microgram) for 24 hr
      affected the inhibition of the tail-flick response induced by CWSS. 5. The ICV or
      IT injection of PTX, CTX, or IBMX did not affect the basal tail-flick response
      latency. 6. It is concluded that spinal, but not supraspinal, PTX-sensitive G
      proteins and cAMP phosphodiesterase may be involved in the antinociception
      produced by CWSS. However, neither spinal nor supraspinal CTX-sensitive G
      proteins appear to be involved in mediating the antinociception induced by CWSS.

PMID- 9147033
TI  - Involvement of GABAB receptors in the antinociception induced by baclofen in the
      formalin test.
AB  - 1. The effect of GABA receptor antagonists on baclofen-induced antinociception
      was examined in rats using the formalin test. Intraperitoneal (IP) administration
      of different doses of baclofen (2.5-10 mg kg-1) to rats induced antinociception
      in both phases of the test. 2. The response was dose-dependent and the maximum
      response was observed with 10 mg kg-1 of the drug. Intracerebroventricular (ICV)
      injection of baclofen (0.5-20 micrograms/rat) also induced dose-dependent
      antinociception in the second phase of the formalin test. 3. The GABAB
      antagonist, phaclofen (1 mg kg-1, IP) but not the GABAA antagonists picrotoxin (1
      mg kg-1, IP) and bicuculline (1.5 mg kg-1, IP), decreased the antinociception
      induced by both ICV and IP administration of baclofen. 4. It is concluded that
      baclofen antinociception in the formalin test is mediated through GABAB receptor
      activation.

PMID- 9147034
TI  - Antiplatelet effects of R,S-(meso)-alpha, alpha'-bis[3-(N,N-diethylcarbamoyl)
      piperidino]-p-xylene ex vivo in the dog and in vivo in the mouse.
AB  - 1. The nipecotamide alpha,alpha'-bis[3-(N,N-diethylcarbamoyl)piperidino]-p-xylene
      (A-1) is a platelet aggregation inhibitor. The meso diastereomer A-1c is superior
      in potency and duration to the synthetic diastereomeric mixture consisting of the
      R,R-, S,S-, and R,S- (meso) isomers in inhibiting collagen-induced platelet
      aggregation ex vivo in the dog. 2. A-1c also is more potent and longer acting
      than A-1 in protecting mice from collagen+epinephrine-induced thromboembolic
      death. 3. The mechanism of antiplatelet action of this compound appears to be
      related to its ability to prevent agonist-induced inhibition of platelet cyclic
      adenosine monophosphate (cAMP) levels.

PMID- 9147035
TI  - Contractile responses and calcium mobilization induced by muscarinic agonists in
      the rat urinary bladder: effects of age.
AB  - In the current study, the contractile responses to muscarinic stimulation of
      urinary bladder strips from young rats and aged rats were compared. 1. The EC50
      values of the two groups in response to bethanechol were similar. 2. The
      magnitude and the velocity of tension generation was significantly lower in
      strips from the aged group. 3. The magnitude as well as the velocity of tension
      generation in response to high K+ solution of the two models were similar. 4. The
      time to peak [Ca2+]i in response to bethanechol was prolonged in strips from the
      aged group as compared with the young group. 5. 45Ca2+ influx in response to
      bethanechol was significantly reduced in the aged group as compared with the
      young group. It is concluded that the reduced contractile response to muscarinic
      stimulation of isolated urinary bladder strips from aged rats is mediated at
      least in part by a decreased rate of Ca2+ entry.

PMID- 9147037
TI  - Evolution of a family of receptors containing multiple C-type carbohydrate
      recognition domains.

PMID- 9147036
TI  - Responsiveness of smooth muscle in the lower urinary tract of rabbits to various
      agonists.
AB  - 1. We compared the responsiveness of smooth muscle in the lower urinary tract and
      prostate from rabbits to the agonists noradrenaline, phenylephrine, clonidine,
      acetylcholine, prostaglandin F2 alpha, and histamine. 2. These agonists
      contracted smooth muscle in the lower urinary tract and prostate. In terms of
      maximal developed tension, contractile responses to the agonists were produced in
      the following order of potency: acetylcholine > prostaglandin F2 alpha >
      histamine > or = phenylephrine > or = noradrenaline > clonidine in the urinary
      bladder body; acetylcholine = noradrenaline = phenylephrine > prostaglandin F2
      alpha > histamine > or = clonidine in the urinary bladder base; noradrenaline >
      or = phenylephrine > or = clonidine > acetyl-choline > prostaglandin F2 alpha >
      or = histamine in the urethra; and noradrenaline > or = phenylephrine > histamine
      = acetylcholine = clonidine = prostaglandin F2 alpha in the prostate. 3. These
      results suggest that considerable responsiveness variation occurs in the lower
      urinary tract and prostate and support the idea that the urinary bladder body is
      primarily governed by cholinergic mechanisms (parasympathetic nerves), whereas
      the urethra and prostate are regulated by alpha 1-adrenergic mechanisms
      (sympathetic nerves) and the bladder base by both.

PMID- 9147038
TI  - Is human galectin-1 activity modulated by monomer/dimer equilibrium?

PMID- 9147039
TI  - Albert Neuberger (1908-96): founder of modern glycoprotein research.

PMID- 9147040
TI  - A unique trisaccharide sequence in heparin mediates the early step of
      antithrombin III activation.
AB  - Spectrofluorimetry experiments using synthetic trisaccharides indicate that in
      compounds that display affinity for antithrombin III (AT-III), a unique
      trisaccharide sequence plays the key role in the early recognition, and the first
      step of AT-III activation. Added to previous observations, these new results
      suggest that the two-step binding mechanism previously proposed (Olson et al., J.
      Biol. Chem., 1981, 256, 11073-11079) might involve, in the first place, a
      conformational change of the protein, induced by the trisasaccharide -->4)-O-(6-O
      sulfo-2-sulfoamino-2-deoxy-alpha-D-glucopyranosyl)-(1 -->4)- O-(beta-D
      glucopyranosyluronic acid)-(1-->4)-O-(3,6-di-O-sulfo-2-sulfoamino-2- deoxy-alpha
      D-glucopyranosyl)-(1-->, then would follow the fitting which ends in the locked
      complex. These observations support the new paradigm invoking specific
      oligosaccharide sequences in selective interactions of glycosaminoglycans and
      proteins.

PMID- 9147041
TI  - Galactose-induced dimerization of blocked ricin at acidic pH: evidence for a
      third galactose-binding site in ricin B-chain.
AB  - Blocked ricin is a glycoconjugate formed by covalent modification of each of the
      two galactose-binding sites of ricin with affinity ligands derived by
      modification of glycopeptides containing galactose-terminated, triantennary, N
      linked oligosaccharides. Blocked ricin undergoes a pH-dependent reversible self
      association, being predominantly dimeric at neutral pH and monomeric at acidic
      pH. The shift in the monomer-dimer equilibrium towards the monomeric form at
      acidic pH (pH 4) is inhibited by lactose, as shown by size-exclusion
      chromatography. This behavior of blocked ricin can be reproduced in studies with
      isolated blocked B-chain. The effect, which is dependent on the concentration of
      the sugar, is specific for sugars having terminal galactose moieties, or sugars
      having the same orientation of hydroxyl groups at C2 and C4 as galactose. These
      results are interpreted as providing further support for the notion that ricin B
      chain has a third galactose-binding site, which may be important for the
      intracellular trafficking of ricin during intoxication of cells.

PMID- 9147042
TI  - Solution conformation of Lewis a--derived selectin ligands is unaffected by
      anionic substituents at the 3'- and 6'-positions.
AB  - The selectins are a family of proteins that mediate leukocyte tethering and
      rolling along the vascular endothelium. E-, P-, and L-selectin recognize various
      derivatives of the Lewis(a) and Lewis(x) trisaccharides. The distribution of
      negative charges on the Lewis(a) and Lewis(x) oligosaccharides appears to be an
      important factor in their binding by the selectins. Previous work exploring this
      electrostatic dependence found that a series of synthetic anionic trisaccharides,
      3'-sulfo, 3'-phospho, 6'-sulfo, and 3',6'-disulfo Lewis(a)-(Glc), exhibited
      differing selectin inhibitory efficacies. To explore the possibility that these
      differences arise from conformational differences between the sugars, the
      solution structures of these trisaccharides were determined using NMR and
      molecular dynamics simulations. Interproton distances and interglycosidic torsion
      angles were determined at 37 degrees C using NOESY buildup curves and 1D LRJ
      experiments, respectively. Data from both experiments agreed well with
      predictions made from 2000 picosecond unrestrained molecular dynamics
      simulations. We found that 3'-sulfation did not alter the core Lewis(a)
      conformation, a finding that reaffirms the results of previous study. In
      addition, we found that sulfation at the 6' position also leaves the
      trisaccharide conformation unperturbed. This is significant because the proximity
      of the 6'-sulfate group to the fucose ring might have altered the canonical Lewis
      (a) structure. The disulfate exhibited greater flexibility than the other
      derivatives in dynamics simulations, but not so much as to affect NOE and
      heteronuclear coupling constant measurements. Taken together, our findings
      support the use of Lewis(a) as a template onto which charged groups may be added
      without significantly altering the trisaccharide's structure.

PMID- 9147043
TI  - Developmentally regulated expression of peanut agglutinin (PNA)-specific glycans
      on murine thymocytes.
AB  - Intrathymic maturation of T lymphocytes is characterized by variable expression
      of O-linked Gal beta 1,3GalNAc glycans reactive with peanut agglutinin (PNA)
      lectin. Recent studies on human thymocytes show that conversion from PNA+ to PNA-
      phenotype is correlated with increased expression of alpha 2,3 O-linked
      sialyltransferase (ST), which sialylates Gal beta 1,3GalNAc glycans, masking
      their binding sites for PNA. Interestingly, alpha 2,3 O-linked ST expression is
      highest within the regions of the thymus containing the most immature and most
      mature thymocyte subsets, suggesting that PNA-specific glycans are intermittently
      masked by sialylation during thymic selection processes. Here, we studied
      expression of PNA receptors on developing thymocytes in the murine system using
      thymocytes from both normal mice and transgenic mice that are genetically
      arrested at the early phases of T cell development. Our results confirm and
      extend recent findings in the human system by showing that murine T cells
      sequentially progress from PNAlo-->PNAhi-->PNAlo stages during their
      differentiation within the thymus. In addition, our data demonstrate that a
      similar set of polypeptides is variably masked by sialylation throughout T cell
      development.

PMID- 9147044
TI  - Developmental regulation of alpha 1,3-fucosyltransferase expression in CD34
      positive progenitors and maturing myeloid cells isolated from normal human bone
      marrow.
AB  - The adhesive interactions of hemopoietic cells within the bone marrow regulate
      their distribution, growth, and development. Fucosylated structures, of which
      sialyl Lewis x has been most extensively studied, are important ligands for
      selectins, but little is known about their function or regulation during normal
      hemopoietic development. We have studied alpha 1,3-fucosyltransferase activity in
      CD34 positive progenitors and myeloid cells at different stages of maturation
      isolated form normal human bone marrow, together with mRNA levels of Fuc-TIV and
      Fuc-TVII. Enzyme activity measured with H type 2 acceptor was present at all
      stages but was markedly elevated in fractions of early myeloid cells enriched for
      promyelocytes, correlating with the appearance of Lewis x on these cells, and
      thereafter fell progressively as cells matured. Activity measured with
      3'sialyllactosamine was present in CD34+ cells and at all stages of maturation.
      Levels were low in promyelocyte/myelocyte transitional cells and increased,
      relative to those measured with H type 2, during the later stages of maturation;
      these changes correlate directly with a maturation-related increase in sialyl
      Lewis x expression. Using competitive quantitative RT-PCR, mRNA levels of Fuc-TIV
      and Fuc-TVII were similar in CD34+ cells, early myeloid and late myeloid cells.
      The significance of these findings in relation to fucosyltransferase activity,
      the synthesis of selectin ligands and differences between normal cells and
      leukemic cell lines is discussed.

PMID- 9147045
TI  - Cloning and expression of a Xenopus laevis oocyte lectin and characterization of
      its mRNA levels during early development.
AB  - cDNA clones encoding a soluble, calcium-dependent, melibiose-binding lectin from
      Xenopus laevis oocytes have been isolated, characterized, and expressed in
      bacteria. This lectin has been shown by others to be localized in oocyte cortical
      granules where it ultimately is released and participates in the formation of the
      fertilization envelope. A lectin with similar specificity has been purified by
      others from blastula and immunolocalized to specific locations in developing
      embryos, which suggests it may also function after fertilization in regulating
      cell adhesion and migration. We have used melibiose affinity chromatography to
      isolate the oocyte lectin (monomer molecular masses of about 45 and 43 kDa) and
      shown that after exhaustive treatment with N-glycanase, only one major protein
      band at 35 kDa was observed, suggesting that a single polypeptide with variable N
      linked glycosylation is expressed in the oocyte. After obtaining internal peptide
      sequences, a PCR-based cloning approach allowed the isolation of full length
      cDNAs from an ovary lambda gt11 library encoding a protein of 313 amino acids
      with three potential N-linked oligosaccharide sites. Although this lectin, termed
      XL35, requires calcium ions for oligosaccharide binding, its sequence does not
      contain the sequence motif defined for "C-type" lectins. A 6-Histagged from of
      the lectin was expressed in E. coli and purified on a Ni(2+)-NTA column from
      bacterial extracts. The recombinant lectin was active using an agglutination
      assay, and this activity was inhibitable by EDTA and melibiose, properties
      exhibited by the native lectin. Southern blot analysis revealed a single
      hybridizing band, arguing against the existence of a multigene family. Northern
      blot analysis demonstrated that the lectin mRNA is expressed in oocytes and
      remains at relatively high levels through late gastrulae, continuing until
      tadpole stages. The persistence of the lectin mRNA, coupled with results from
      earlier studies, strongly suggests that XL35 is zygotically expressed and
      functions during morphogenesis.

PMID- 9147046
TI  - Structure of a glycoconjugate in solution and in complex with an antibody Fv
      fragment.
AB  - By use of heteronuclear (13C, 1H) NMR methods, the three-dimensional structure
      and dynamics of the glycoconjugate estrone-3-glucuronide (E3G) uniformly 13C
      enriched in the glucuronic acid moiety has been probed both in free solution and
      in association with an anti-E3G antibody single-chain Fv fragment. The glycan is
      found to exist in multiple conformations in free solution, with particularly
      large torsional fluctuations about the glycosidic linkage psi. Resonance
      assignments and distance restraints for the glycoconjugate in the bound state
      were obtained from heteronuclear proton-carbon-carbon-proton-COSY and isotope
      edited NOESY techniques, respectively. Quantitation of the NOE data with a full
      relaxation matrix approach showed that the antibody selects a conformation from
      the solution repertoire which does not correspond with either of the two lowest
      energy conformations of the free glycan, and the internal energy of the glycan in
      the bound state is estimated to be at most approximately 15 kcal/mol higher than
      the global minimum energy conformation. The glucuronide moiety undergoes a
      stacking interaction with an aromatic ring in the binding site, and both ring
      current shifts and nuclear Overhauser effects computed from the predicted bound
      state conformation are in good agreement with experiment. The bound-state
      conformation is also in good agreement with preliminary x-ray data on a related
      complex.

PMID- 9147047
TI  - Terminal beta-linked tyvelose creates unique epitopes in Trichinella spiralis
      glycan antigens.
AB  - Indirect evidence that the immunodominant N-glycans of the parasite, Trichinella
      spiralis are capped by novel beta-linked 3,6-dideoxy-D-arabinohexopyranosyl
      residues (tyvelose, Tyv) was obtained from immunochemical assays employing
      monoclonal antibodies and synthetic oligosaccharides. Three of four previously
      characterized monoclonal antibodies generated from the lymphocytes of T.spiralis
      infected rats bind BSA glycoconjugates bearing the synthetic epitope beta-D
      Tyvp(1-->3)-beta-D-GalNAcp but not to the corresponding alpha-D-Tyvp(1-->3)-beta
      D-GalNAcp-BSA glycoconjugate. Monosaccharide and disaccharide glycoside
      inhibition data mirrors the results of the direct binding experiments. The
      branched tetrasaccharide beta-D-Tyv(1-->3)-beta-D-GalNAcp(1-->4)[alpha-L-Fucp(1 -
      >3)] beta-D-GalNAcp is the most active synthetic oligosaccharide inhibitor for
      all four monoclonal antibodies studied, while the corresponding alpha-D-Tyv
      containing tetrasaccharide and the core trisaccharide beta-D-GalNAcp(1-->4)[alpha
      L-Fucp(1-->3)]beta-D-GlcNAcp+ ++ are inactive. The exceptional inhibitory
      activity of the disaccharide beta-D-Tyvp(1-->3)-beta-D-GalNAcp with one mAb (18H)
      compared to that of the branched tetrasaccharide beta-D-Tyvp(1-->3)-beta-D
      GalNAcp(1-->4)[alpha-L-Fucp( 1-->3)]-beta-D-GlcNAcp is indicative of the presence
      of linear, nonfucosylated glycan epitopes (beta-D-Tyvp(1-->3)-beta-D-GalNAcp(1-
      >4) beta-D-GlcNAcp) that lack a fucose residue in one arm of the antigenic, tetra
      antennary N-glycan. This observation supports earlier FAB-mass spectrometry
      evidence for the existence of tetra-antennary, core fucosylated glycans that lack
      a fucose residue on one of their antennae.

PMID- 9147048
TI  - Association of the major ganglioside in sea urchin eggs with yolk lipoproteins.
AB  - The predominant ganglioside in sea urchin eggs, M5 (NeuGc alpha 2-6Glc beta 1
      1'Cer), exists mainly in the cytoplasm before and after fertilization. Using
      immunofluorescence microscopy, M5 ganglioside has been shown to localize in the
      network of cortical endoplasmic reticulum and unidentified vesicles in the eggs.
      In this study, the subcellular localization of M5 ganglioside in unfertilized
      eggs was further examined by immunoelectronmicroscopy using preembedding and
      postembedding labeling techniques. In order to prevent lipid extraction during
      dehydration and embedding, fixed eggs were subjected to rapid-freezing and freeze
      substitution, and then embedded in hydrophilic resin. When ultrathin sections
      were treated with the anti-M5 ganglioside monoclonal antibody, the labeling of M5
      ganglioside localized in the endoplasmic reticula, yolk granules, and microvilli.
      M5 ganglioside in yolk granules was not restricted to the membrane, suggesting
      that M5 ganglioside associated with soluble proteins or components in yolk
      granules. Indeed, gel filtration of the soluble fraction of the yolk lysate
      showed that M5 ganglioside was coeluted with yolk lipoproteins which were one of
      the main components in yolk granules. Moreover, M5 ganglioside was extracted from
      the electrophoretically purified yolk lipoproteins. These results demonstrate
      that M5 ganglioside in yolk granules associate with yolk lipoproteins. These data
      suggest that much of M5 ganglioside may be taken up into growing oocytes during
      oogenesis and transported from yolk granules to other cellular components during
      embryogenesis. M5 ganglioside associating with yolk lipoproteins in yolk granules
      may be a significant stored material to be utilized for early embryogenesis.

PMID- 9147049
TI  - Structure-function relationships in glucosidase I: amino acids involved in
      binding the substrate to the enzyme.
AB  - As the enzyme that initiates the maturation phase of the oligosaccharide moiety
      of N-linked glycoproteins, glucosidase I controls the flux of carbohydrate during
      the biosynthesis of these proteins. In a previous study to elucidate the
      structure-function relationships, we reported the presence of a cysteine residue
      at or near the active site of the enzyme from the bovine mammary gland
      (Pukazhenthi,B.S., Muniappa,N. and Vijay,I.K., 1993, J. Biol. Chem., 268, 6445
      6452). We have now extended this approach to identify the participation of an
      arginine and a tryptophan residue in the enzyme that may play an important role
      in binding the substrate. The data have been combined with the results of the
      previous study and the cDNA-derived sequence to propose a ERHLDLRCW motif in the
      active site of the enzyme in the rat mammary gland that is involved in binding
      the incipient glycoprotein substrate for processing.

PMID- 9147050
TI  - Sulfation of sialyl lactosamine oligosaccharides by chondroitin 6
      sulfotransferase.
AB  - We have previously shown that chondroitin 6-sulfotransferase (C6ST) catalyzes
      transfer of sulfate not only to position 6 of GalNAc residue of chondroitin but
      also to position 6 of Gal residue of keratan sulfate. In this study, we examined
      the sulfation of sialyl lactosamine oligosaccharides by C6ST. C6ST catalyzed
      transfer of sulfate to NeuAc alpha 2-3Gal beta 1-4GlcNAc (SLN), NeuAc alpha 2
      3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4GlcNAc (SL1L1), NeuAc alpha 2-3Gal beta 1
      4(6-sulfo)GlcNAc beta 1-3(6-sulfo)Gal beta 1-4(6-sulfo)GlcNAc (SL2L4), and their
      desialylated derivatives, but not to NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1
      3)GlcNAc (SLe(x)). The sulfated product formed from SLN was degraded with
      neuraminidase and reduced with NaBH4. The resulting sulfated disaccharide alditol
      showed the same retention time in SAX-HPLC as that of [3H]Gal(6SO4) beta 1
      4GlcNAc-ol. The sulfated product formed from SLN was also degraded by a reaction
      sequence of neuraminidase digestion, hydrazinolysis, deamination, and NaBH4
      reduction. The final product was coeluted with [3H]Gal(6SO4) beta 1
      4anhydromannitol in SAX-HPLC. These observations show that C6ST could transfer
      sulfate to position 6 of Gal residue of SLN. Incorporation of sulfate into SL2L4
      was much higher than the incorporation into SL1L1, suggesting that sulfate moiety
      attached to adjacent GlcNAc residue may stimulate the transfer of sulfate to Gal
      residue. The recombinant C6ST also catalyzed sulfation of the sialyl lactosamine
      oligosaccharides, indicating that a single protein catalyzes sulfation of
      chondroitin, keratan sulfate, and sialyl lactosamine oligosaccharides. These
      results raised a possibility that C6ST may be one of the candidates involved in
      the biosynthesis of sulfated sialyl Lewis x ligand for L-selectin.

PMID- 9147051
TI  - Identification of a major human high molecular weight salivary mucin (MG1) as
      tracheobronchial mucin MUC5B.
AB  - Human saliva contains high and low molecular weight mucin glycoproteins, that are
      distinct. Recently the gene encoding low molecular weight salivary mucin was
      cloned and designated MUC7, whereas the primary structure of high molecular
      weight salivary mucin is unclear. Furthermore, the expression patterns of high
      and low molecular weight salivary mucins in salivary glands have been debated. We
      have previously generated monoclonal antibodies specific for the peptide cores of
      salivary mucins. In the present study a monoclonal antibody specific for high
      molecular weight salivary mucin was used to screen a human salivary gland cDNA
      library. A single clone, SAL1, was identified and found to be encoded by
      tracheobronchial mucin gene MUC5B. A previously reported partial cDNA sequence
      from salivary mucin was linked to SAL1/MUC5B by genomic cloning and reverse
      transcriptase-polymerase chain reaction. Northern analysis of salivary gland RNA
      probed with SAL1 suggested that MUC5B was highly expressed in salivary glands. In
      situ hybridization was performed with a SAL1/MUC5B probe and a MUC7 probe. All
      mucous cells from the submandibular, sublingual, palatine, and labial glands
      labeled with the MUC5B probe, while serous cells labeled with the MUC7 probe.
      These findings were in accordance with our previous immunohistological results of
      the cellular localizations of salivary mucins. The results suggest that MUC5B is
      identical to or a major fraction of high molecular weight salivary mucin, and
      that MUC5B is expressed in all mucous cells of salivary glands. In contrast MUC7
      is expressed in serous cells of salivary glands except the parotid glands.

PMID- 9147052
TI  - New sialic acids from biological sources identified by a comprehensive and
      sensitive approach: liquid chromatography-electrospray ionization-mass
      spectrometry (LC-ESI-MS) of SIA quinoxalinones.
AB  - Sialic acids are a family of 9-carbon carboxylated sugars, where different
      substitutions of the backbone define over 30 members. Biological roles of these
      substitutions have been missed until recently because of their low abundance and
      lability to conventional isolation/purification methods. This new approach
      characterizes sialic acids using electrospray ionization-mass spectrometry (ESI
      MS) to monitor the HPLC separation of their DMB (1,2-diamino-4,5-methylenedioxy
      benzene) derivatives (quinoxalinones). A combination of retention times and
      spectra characteristics allows definition of the type and position of the various
      substituents. This approach requires no previous purification, involving a simple
      derivatization reaction followed by direct injection on the microbore HPLC
      column. A complete spectrum, including molecular ions and CAD fragments of a
      sialic acid quinoxalinone, is obtained by injecting 10-20 pmol of the compound.
      Individual quinoxalinones can be purified by regular RP-HPLC and analyzed by
      direct-injection ESI-MS or LSIMS. Using this approach, we identified 28 different
      sialic acids, including the following new species: Neu5Gc9Lt (BSM), anhydro
      derivatives of Neu5Ac other than the 4,8-anhydro (horse serum hydrolyzates),
      KDN5(7)Ac and KDN5(7),9Ac2 (amphibian Pleurodeles waltl), four isomers of
      Neu5Gc8MexAc and three anhydro derivatives of Neu5Gc8Me (glycolipids of the
      starfish Pisaster brevispinus), and Neu5Ac8S (in addition to Neu5Gc8S, in the
      glycolipids of the sea urchin Lovenia cordiformis). Results show the usefulness
      of LC-ESI-MS to study sialic acid diversity, and identification of small amounts
      of unexpected sialic acids or new members of their family.

PMID- 9147053
TI  - Isolation and characterization of an alpha 1,2-mannosidase cDNA from the
      lepidopteran insect cell line Sf9.
AB  - As part of our ongoing efforts to characterize the N-glycosylation pathway of
      lepidopteran insect cells, we have isolated an alpha 1,2-mannosidase homolog from
      an Sf9 cDNA library. This cDNA contains an open reading frame which encodes a 670
      amino acid protein with a calculated molecular weight of 75,225 Da. This protein
      has two potential N-glycosylation sites, two consensus calcium binding sequences,
      and is predicted to be a type II integral membrane protein with a 22 amino acid
      transmembrane domain (residues 31-52). The amino acid sequence of this protein is
      35-57% identical to Drosophila, human, murine, and yeast alpha 1,2-mannosidases.
      A transcript of approximately 6 kilobases was detected by Northern blot analysis
      of Sf9 mRNA. Genomic Southern blots probed with an intron-free fragment of the
      alpha 1,2-mannosidase gene indicated that there are at least two copies or cross
      hybridizing variants of this gene in the Sf9 genome. In vivo expression of the
      cDNA using a recombinant baculovirus produced a protein that released [3H]mannose
      from [3H]Man9GlcNAc. This activity required calcium, but not magnesium, and was
      inhibited by 1-deoxymannojirimycin. These results indicate that Sf9 cells encode
      and express an alpha 1,2-mannosidase with properties similar to those of other
      eukaryotic processing alpha 1,2-mannosidases.

PMID- 9147054
TI  - Directed mutagenesis of the Trypanosoma cruzi trans-sialidase enzyme identifies
      two domains involved in its sialyltransferase activity.
AB  - Of the increasing number of sialidases found to be made by microorganisms, the
      trypanosome trans-sialidase is unique in its added ability to efficiently carry
      out a sialyltransferase reaction using preformed glycoconjugates. The enzyme is
      predicted to have a multidomain structure, with one domain containing sequence
      and expected structural features found in bacterial sialidases. The trans
      sialidase is very similar in overall sequence to another trypanosome enzyme that
      has only sialidase activity. Hybrid expression constructs containing pieces of
      these trypanosome trans-sialidase and sialidase genes were used to determine
      which regions of trans-sialidase are required for sialyltransferase activity. Two
      domains were found to influence the enzymatic activity: the N-terminal catalytic
      domain, and a downstream domain that resembles an Fn3-like module.

PMID- 9147055
TI  - Agaricus bisporus lectin binds mainly O-glycans but also N-glycans of human IgA
      subclasses.
AB  - The primary interaction between purified Agaricus bisporus lectin (ABL) and human
      IgA subclasses was studied by ABL-affinity chromatography, dot blot assay and
      competitive enzyme-lectin assay, considering that ABL could be an alternative
      tool for detection of IgA1 O-glycans. Both secretory IgA subclasses bound to ABL
      Sepharose and the IgA2 subclass (which contains only N-glycans) was recovered
      with a high degree of purity when NH4OH was used as eluent. ABL-Ig interaction
      was also observed by dot blot assays using ABL-peroxidase against monoclonal IgA1
      k Pan, IgA2m(1)k Gir, IgA2m(2)k Bel, secretory IgA2 and normal IgG (also contains
      only N-glycans). When these immunoglobulins were enzymatically treated with
      peptide N-glycosidase F (N-glycan hydrolysis), the ABL-IgA2 and -IgG interaction
      did not occur while IgA1 maintained a high degree of interaction with ABL. Also,
      the ABL-IgA interaction was observed by competitive enzyme-lectin assay, and when
      IgA1 subclass was treated with endo-alpha-N-acetylgalactosaminidase for O-glycans
      hydrolysis, the reactivity with ABL was very low. We conclude that the
      complementary use of ABL and peptide N-glycosidase F could be a useful tool to
      assess the O-glycosylation state of human IgA1 subclass, which is of relevant
      importance in the effector functions of immunoglobulins.

PMID- 9147056
TI  - Characterization of a 180 kDa molecule apparently reactive with recombinant L
      selectin.
AB  - In the present study we identified a 180 kDa molecule (p180) in rat lymph nodes
      (LN) apparently reactive with silkworm derived recombinant L-selectin (LEC-IgG)
      in a Ca(2+)-dependent manner. Analysis of amino acid sequence revealed that p180
      has a strong homology to the macrophage mannose receptor (MMR), which was
      corroborated by the observation that p180 reacted with polyclonal anti-alveolar
      MMR antibody and mannosyl-BSA-agarose. In agreement with this notion, the binding
      of p180 to the silkworm LEC-IgG was inhibited by alpha-methyl-D-mannoside.
      However, in sharp contrast to its reactivity against the silkworm LEC-IgG, p180
      failed to bind LEC-IgG produced by COS-7 cells, suggesting that p180 reacted with
      the silkworm LEC-IgG through the recognition of oligomannose-type
      oligosaccharides expressed on the silkworm products and that the lectin activity
      of L-selectin was not involved in the interaction. These results, together with
      the immunohistochemical studies showing that p180 was absent from the majority of
      high endothelial venules (HEV) but present in medullary macrophages, led us to
      conclude that p180 obtained from LN lysates by the use of the silkworm LEC-IgG is
      not a physiological ligand for L-selectin, warning against the use of recombinant
      proteins expressed in the baculovirus/ silkworm expression system for the
      detection of carbohydrate ligands.

PMID- 9147057
TI  - Isolation and characterization of lectins and lectin-alliinase complexes from
      bulbs of garlic (Allium sativum) and ramsons (Allium ursinum).
AB  - A procedure developed to separate the homodimeric and heterodimeric mannose
      binding lectins from bulbs of garlic (Allium sativum L.) and ramsons (Allium
      ursinum L.) also enabled the isolation of stable lectin-alliinase complexes.
      Characterization of the individual lectins indicated that, in spite of their
      different molecular structure, the homomeric and heteromeric lectins resemble
      each other reasonably well with respect to their agglutination properties and
      carbohydrate-binding specificity. However, a detailed analysis of the lectin
      alliinase complexes from garlic and ramsons bulbs demonstrated that only the
      heterodimeric lectins are capable of binding to the glycan chains of the
      alliinase molecules (EC 4.4.1.4). Moreover, it appears that only a subpopulation
      of the alliinase molecules is involved in the formation of lectin-alliinase
      complexes and that the complexed alliinase contains more glycan chains than the
      free enzyme. Finally, some arguments are given that the lectin-alliinase
      complexes do not occur in vivo but are formed in vitro after homogenization of
      the tissue.

PMID- 9147058
TI  - Optimizing lectin-carbohydrate interactions: improved binding of divalent alpha
      mannosylated ligands towards Concanavalin A.
AB  - The synthesis and binding properties to Jack bean phytohaemagglutinin in
      (Concanavalin A, Con A) of a new family of divalent alpha-D-mannopyranoside
      ligands are described. The synthesis of these ligands is based on the coupling of
      commercially available diamines to p-isothiocyanatophenyl 2,3,4,6 tetra-O-acetyl
      alpha-D-mannopyranoside (4). The resulting dimers 6, 15 to 22 and 30 were tested
      for their relative inhibitory potency by solid-phase enzyme-linked lectin assays
      (ELLA) using methyl alpha-D-mannopyranoside as standard. Divalent mannosylated
      ligand 35 bearing a non-aromatic aglycon was also tested for comparison purposes.
      Concentrations necessary for 50% inhibition (IC50s) of binding of yeast mannan to
      Jack bean phytohaemagglutinin (Con A) were determined. The inhibitions showed
      dimers to be approximately 10- to 90-fold more potent than methyl alpha-D
      mannopyranoside. Variations in the intra-mannosyl distance proved to be an
      important factor for optimum binding.

PMID- 9147059
TI  - Difference in binding-site architecture of the serum-type and liver-type mannose
      binding proteins.
AB  - The carbohydrate-recognition domains (CRDs) of the serum-type and the liver-type
      mannose-binding proteins (MBPs) from rat display different binding
      characteristics toward mannose-rich oligosaccharides derived from N-glycosides,
      despite the overall similarity in their binding site architecture, oligomeric
      status and actual binding specificity at the monosaccharide level. We found that
      the liver-type MBP CRD of rat (MBP-C) bound methyl glycosides of certain
      mannobioses and -trioses, which are part of the mannose-rich N-glycoside, more
      tightly than methyl alpha-mannopyranoside. In contrast, the serum-type MBP CRD of
      rat (MBP-A) bound all the methyl glycosides of manno-oligosaccharide and methyl
      alpha-mannopyranoside with similar affinities. The mannobiose and -triose most
      strongly bound to MBP-C CRD were Man alpha (1-2)Man alpha-OMe and Man alpha (1
      2)Man alpha (1-6)Man alpha-OMe, respectively. From these and other data, we
      postulate that the binding site of MBP-C has an extended area of interaction,
      probably the size of a mannotriose, while MBP-A interacts essentially with one
      mannose residue.

PMID- 9147060
TI  - A comparative study of lectin binding to cultured chick sternal chondrocytes and
      intact chick sternum.
AB  - Cultured chondrocytes derived from the caudal and cephalic ends of embryonic
      chick sterna have been compared with each other and with whole sternum, by using
      a panel of 21 lectins to probe the distribution of oligosaccharides in
      glycoconjugates of cells and matrix at various times of culture or development.
      On culture in collagen gels, the cells changed their morphology with time,
      degrading glycan in the surrounding culture medium and depositing new matrix, the
      glycan content of which reflected the site of origin of the cells, indicating
      that the glycan phenotype of both cells and matrix ('glycotype') was
      predetermined and persistent. Sterna of embryonic chicks showed unexpected
      complexity in their distribution pattern of glycan, containing at least six
      distinct regions. Major regional temporal differences were evident among
      saccharides terminating in alpha-N-acetyl galactosamine and beta-galactose, while
      changes in glycans terminating in fucose, sialic acid and alpha-mannose were
      somewhat less marked. Subsets of complex N-glycans changed little.

PMID- 9147061
TI  - Establishment of a monoclonal antibody directed against Gb3Cer/CD77: a useful
      immunochemical reagent for a differentiation marker in Burkitt's lymphoma and
      germinal centre B cells.
AB  - A new monoclonal antibody (TU-1) directed against the Gal alpha 1-4Gal beta 1
      4Glc residue of the Gb3Cer/CD77 antigen was prepared by the hybridoma technique
      following immunization of mice with an emulsion composed of monophosphoryl lipid
      A, trehalose dimycolate, and Gb3Cer isolated from porcine erythrocytes. TU-1
      showed reactivity towards Gb3Cer and lyso-Gb3Cer(Gal alpha 1-4Gal beta 1-4Glc
      beta 1-1'Sph), although the reactivity towards lyso-Gb3Cer was about 10-fold
      lower than that to Gb3Cer. But it did not react with other structurally-related
      glycolipids, such as LacCer (Gal beta 1-4Glc beta 1-1'Cer), Gg3Cer, Gg4Cer,
      Gb4Cer (GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc beta 1-1'Cer),
      galactosylparagloboside (Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc
      beta 1-1'Cer), sulfatide (HSO3-3Gal beta 1-1'Cer), other gangliosides (GM3, GM2,
      GM1a, GD1a and GT1b), or P1 antigen (Gal alpha 1-4Gal beta 1-4GlcNAc beta 1-3Gal
      beta 1-4Glc beta 1-1'Cer) among neutral glycolipids prepared from P1 phenotype
      red blood cells. Furthermore, TU-1 reacted with viable lymphoma cells, such as
      human Burkitt lymphoma cell line, Daudi, and Epstein-Barr virus (EBV)-transformed
      B cells by the immunofluorescence method, and also with germinal centre B cells
      in human tonsil and vessel endothelial cells in human thymus histochemically.
      These results indicate that TU-1 is a monoclonal antibody directed against
      Gb3Cer/CD77 antigen and can be utilized as a diagnostic reagent for Burkitt's
      lymphoma and also for detection of the blood group Pk antigen in glycolipid
      extracts of erythrocytes.

PMID- 9147062
TI  - Structural analysis of neutral glycosphingolipids from Ascaris suum adults
      (Nematoda:Ascaridida).
AB  - The neutral glycosphingolipid fraction from adults of the pig parasitic nematode,
      Ascaris suum, was resolved into four components on thin-layer chromatography. The
      high-performance liquid chromatography-isolated components were structurally
      analysed by: methylation analysis; exoglycosidase cleavage; gas-liquid
      chromatography/mass spectrometry; liquid secondary-ion mass spectrometry; and, in
      particular, matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry. Their chemical structures were determined as: Glc(beta 1
      1)ceramide, Man(beta 1-4)Glc(beta 1-1)ceramide, GlcNAc(beta 1-3)Man(beta 1
      4)Glc(beta 1-1)ceramide and Gal(alpha 1-3)GalNAc(beta 1-4)GlcNAc(beta 1
      3)Man(beta 1-4)Glc(beta 1-1)ceramide; and were characterized as belonging to the
      arthro-series of protostomial glycosphingolipids. No glycosphingolipid component
      corresponding to ceramide tetrasaccharide was detected during these analyses. The
      ceramide composition of the parent glycosphingolipids was dominated by the 2-(R)
      hydroxy C24:0 fatty acid, cerebronic acid, and C17 sphingoid-bases: 15
      methylhexadecasphing-4-enine and 15-methylhexadecaphinganine in approximately
      equal proportions. The component ceramide monohexoside was characterized by an
      additional 15-methylhexadecaphytosphingosine.

PMID- 9147063
TI  - Structural changes of immunoglobulin G oligosaccharides with age in healthy human
      serum.
AB  - Age-related changes of IgG N-linked oligosaccharides isolated from normal human
      serum are reported for 403 individuals (male 227 and female 176), varying in age
      from 0 to 85 years. The IgG N-linked oligosaccharides were released from the
      protein by digestion with a glycoamidase and reductively aminated with the
      fluorescent reagent, 2-aminopyridine. The mixture of pyridylaminated
      oligosaccharides was separated at high resolution by HPLC using a reverse-phase
      column. From the results of neutral oligosaccharide analysis, agalactosyl
      glycoform and bisecting GlcNAc-containing glycoform were shown to increase with
      increasing age. Spearman's correlation coefficients were 0.503 and 0.473,
      respectively. Thus, in healthy people, an increase of both types of glycoforms
      correlates weakly with age. In addition, differences were demonstrated between
      male and female groups in their twenties. The quantity of agalactosyl glycoform
      was found to be lower in females than in males. No significant differences,
      however, were observed in the quantity of bisecting GlcNAc-containing glycoforms
      between males and females.

PMID- 9147064
TI  - Murine hepatic beta-galactoside alpha 2,6-sialyltransferase gene expression
      involves usage of a novel upstream exon region.
AB  - ST6Gal I (beta-galactoside alpha 2,6-sialyltransferase, SiaT-1, ST6N, EC
      2.4.99.1) mediates the attachment of the alpha 2,6-sialyl linkage common on N
      linked glycans. Previous work suggests substantial inter-species conservation in
      SIAT1, the gene encoding ST6Gal I. In human and in rat, hepatic-specific SIAT1
      transcription is initiated at Exon I. Here we report a surprising departure in
      the structural organization of the murine ST6Gal I gene. By a combination of
      primer extension analysis, 5'-RACE analysis, and analysis of genomic sequences,
      we show that the murine hepatic ST6Gal I mRNA contains a novel region 5' of Exon
      I. This novel sequence is encoded on a discrete upstream exon, Exon H. In
      contrast to human and rat hepatic ST6Gal I, the murine mRNA is transcriptionally
      initiated at the start of Exon H. Differential mRNA blot analysis indicates that
      transcripts containing Exon H sequences are preferentially expressed in liver.

PMID- 9147066
TI  - Absence of nitric oxide synthase I despite the presence of the dystrophin complex
      in human striated muscle.
AB  - Recently, it has been shown that in human striated muscle the signalling enzyme,
      brain-type nitric oxide synthase I (NOS I), is associated with the sarcolemma and
      complexes with dystrophin and/or members of the dystrophin complex. In order to
      find out whether there exists a regular association between NOS I and the
      complex, muscle biopsies from patients with various muscle disorders were
      analysed by enzyme histochemistry and immunohistochemistry. In patients suffering
      from Duchenne muscular dystrophy, and to a lesser extent in those with Becker
      type dystrophy, NOS I and dystrophin complex components were absent or
      drastically reduced in the sarcolemma region. In other dystrophies, as well as in
      metabolic and inflammatory myopathies, NOS I and dystrophin complex constituents
      were expressed normally, while in the case of neurogenic diseases leading to
      denervation atrophy and especially congenital idiopathic clubfoot, the
      immunohistochemical patterns of the distribution of the dystrophin complex
      constituents were normal, but NOS I activity and protein were deficient or
      dramatically diminished. The results can be interpreted as indicating that, in
      general, NOS I targeting to the sarcolemma is dependent on particular members of
      the dystrophin complex, such as alpha-1 syntrophin, yet the expression and/or
      positioning of NOS I may be under the control of further factors, probably of
      neurogenic origin. NOS I-associated diaphorase may thus be a useful complementary
      tool in the diagnosis of muscle disorders.

PMID- 9147065
TI  - Insulin-stimulated Glut 4 translocation in human skeletal muscle: a quantitative
      confocal microscopical assessment.
AB  - Insulin stimulation of glucose transport in skeletal muscle is considered to
      involve translocation of the skeletal muscle/adipose tissue glucose transporter
      isoform, Glut 4, from cytosolic vesicles to the cell surface. The current study
      was undertaken to investigate Glut 4 translocation in skeletal muscle of healthy
      volunteers during euglycaemic insulin infusion. Previous quantitative studies of
      glucose transport have depended on differential centrifugation methods, which
      demand large biopsy samples. In this study we have developed and applied a
      quantitative method using confocal laser microscopy, well suited to the small
      needle biopsies that are typically available clinically. Percutaneous biopsy of
      vastus lateralis skeletal muscle was performed during basal and euglycaemic
      insulin-stimulated conditions, and Glut 4 translocation was assessed using
      immunohistochemical labelling and confocal laser microscopy imaging in 14 healthy
      lean subjects. At physiological hyperinsulinaemia (536 +/- 16 pM), mean systemic
      glucose utilization was 9.27 +/- 0.78 mg/kg-min, indicative of normal insulin
      sensitivity. The presence of Glut 4 at the sarcolemma increased significantly (p
      < 0.01), with a ratio of insulin-stimulated to basal sarcolemmal Glut 4 of 1.85
      +/- 0.33, indicative of insulin-stimulated Glut 4 translocation. The area of Glut
      4-labelled sites also increased significantly (p < 0.01) in response to insulin
      infusion; this ratio was 1.56 +/- 0.13. Thus, at physiological hyperinsulinaemia,
      the amount of Glut 4 at the cell surface of skeletal muscle in healthy, lean
      individuals increases approximately twofold over basal conditions, and this
      process can be measured using immunohistochemical labelling imaged by confocal
      laser scanning microscopy.

PMID- 9147067
TI  - A novel monoclonal antibody, RM-4, specifically recognizes rat macrophages and
      dendritic cells in formalin-fixed, paraffin-embedded tissues.
AB  - An anti-rat macrophage/dendritic cell monoclonal antibody, RM-4, was produced
      using a homogenate of silica-induced lung granulomas of rat as immunogen.
      Immunohistochemistry demonstrated that RM-4 was specific for macrophage and
      dendritic cell populations residing in various organs and tissues. It did not
      react with any cells other than macrophage/dendritic cells. In the double
      staining of the spleen, RM-4-positive macrophages showed wider distribution than
      those of the four other anti-rat macrophage monoclonal antibodies compared. The
      immunoreactivity of RM-4 was well preserved not only in frozen sections but also
      in formalin-fixed, paraffin-embedded tissues. The isotype of the monoclonal
      antibody was IgG1 kappa and its antigen molecular weight was 46 kDa.
      Immunoelectron microscopy revealed positive reaction products for RM-4 on the
      membrane of endosomes and lysosomes in macrophages and epidermal Langerhans
      cells. Reaction intensity increased after thioglycolate elicitation or
      endocytosis regardless of ingested materials. From these data, it is concluded
      that RM-4 recognizes a membrane protein of endolysomes in macrophages and
      dendritic cells. The antigen may play a role in endolysosomal processing. RM-4 is
      considered to be a useful tool not only for identifying macrophage/dendritic
      cells both in frozen and paraffin-embedded tissues, but also for evaluating their
      endolysosomal processing.

PMID- 9147068
TI  - Detection of guanylate cyclases A and B stimulated by natriuretic peptides in
      gastrointestinal tract of rat.
AB  - The ultracytochemical localization of membrane-bound guanylate cyclases A and B
      has been studied after stimulation with atrial natriuretic peptide, C-type
      natriuretic peptide and brain natriuretic peptide in the gastrointestinal tract
      of rat. The two isoforms are stimulated differently by the three peptides. The
      results showed that the atrial and C-type natriuretic peptides stimulated
      guanylate cyclase activity, whereas the brain peptide seemed not to activate
      enough of the enzyme to detect. The guanylate cyclase activity had a wider
      distribution in stomach and small intestine than in large intestine;
      nevertheless, the reaction product of guanylate cyclase A activity had a wider
      localization in the stomach, whereas the reaction product of guanylate cyclase B
      activity had a wider distribution in the small intestine. In the small and large
      intestine, we detected mostly similar localizations of guanylate cyclase activity
      irrespective of the peptide used; in the stomach the reaction products of
      guanylate cyclase A and B were detected in different cell types or in different
      sites of the same cell. In all the gastrointestinal tract, guanylate cyclase
      activity was detected mainly in three types of cells: exocrine and endocrine
      cells; undifferentiated and mature epithelial cells; and smooth muscle cells.
      These localizations of guanylate cyclase activity suggest its role in regulating
      glandular secretion, cellular proliferation and muscular activity.

PMID- 9147069
TI  - Expression of retinoid-X receptors (-alpha,-beta,-gamma) and retinoic acid
      receptors (-alpha,-beta,-gamma) in normal human skin: an immunohistological
      evaluation.
AB  - Increasing evidence suggests that the retinoid-X receptors (RXR-alpha,-beta,
      gamma) play a crucial role in regulating the transcriptional activity of several
      steroid hormone receptors, including the receptors for retinoic acid (RAR-alpha,
      beta,-gamma), 1,25-dihydroxyvitamin D3 and thyroid hormone. We investigated the
      localization of the different types of RXR-alpha,-beta,-gamma and RAR-alpha,
      beta,-gamma proteins in frozen sections of normal human skin (n = 12) in situ,
      applying recently raised corresponding specific monoclonal antibodies and an
      immunohistochemical technique that we established for the detection of these
      nuclear receptors. Our findings indicate that RXR-alpha,-beta,-gamma and RAR
      alpha,-beta,-gamma proteins can be detected by immunohistochemistry in normal
      human skin. In contrast to RXR-alpha,-beta,-gamma as well as RAR-alpha and RAR
      gamma proteins that were consistently detected in cell layers of the viable
      epidermis, RAR-beta was only focally demonstrated in single epidermal cells in
      three out of 12 biopsies analysed. Immunohistochemical labelling of RAR-alpha,
      beta,-gamma and RXR-alpha,-beta,-gamma proteins in epidermal nuclei was also
      pronounced in the stratum granulosum, suggesting a function of RXR and RAR
      proteins in the transition from proliferation to differatiation in epidermal
      keratinocytes. Expression of RXRs and RARs in hair follicles, sebaceous glands
      and endothelial cell points to a biological function from these nuclear receptors
      to hair growth as well as to the physiology of sebaceous glands and endothelial
      cells.

PMID- 9147070
TI  - Expression of the acatalytic carbonic anhydrase VIII gene, Car8, during mouse
      embryonic development.
AB  - The carbonic anhydrase (CA)-like protein, CA VIII, lacks the typical carbon
      dioxide hydrase activity of the CA isozymes. However, the high degree of amino
      acid sequence similarity between the products of the mouse and the human CA VIII
      genes suggests an important biological function. We have attempted to investigate
      the function of this gene in mammalian development by conducting an in situ
      hybridization study on sagittal sections of mouse embryos at gestation days of
      9.5-16.5 using a 35S-labelled riboprobe. Results indicate that this gene (called
      Car8 in mice) is expressed as early as day 9.5 in a variety of organs including
      liver, branchial arches, neuroepithelium and developing myocardium. Between days
      10.5 and 12.5, it showed a widespread distribution of mRNA expression that became
      more restricted as development progressed. The level of expression of Car8 mRNA
      was relatively high in the brain, liver, lung, heart, gut, thymus and epithelium
      covering the head and the oronasal cavity.

PMID- 9147071
TI  - Correlative histochemical study providing evidence for the dual nature of human
      colorectal cancer mucin.
AB  - Luminal secretions within colorectal cancers have been assumed to be the
      counterpart of normal goblet cell mucin. The aim of this study was to establish
      whether secretory material within colorectal cancers may in fact be traced to
      different lineages: goblet cells and columnar cells. The distribution of the
      apomucins MUC1 and MUC2, non-O-acetylated sialic acid and the carbohydrate
      structures sialosyl Tn, Tn, Lewis(x), sialosyl Lewis(x) and Lewis(y) was studied
      in normal colorectal mucosa and colorectal cancer specimens using standard
      histochemical techniques. Unmasking of MUC1 and MUC2 was achieved using periodic
      acid and saponification-neuraminidase-periodic acid pretreatment respectively.
      Within normal and malignant epithelium, correlations and/or co-localization could
      be demonstrated for goblet cells with MUC2, non-O-acetylated sialic acid,
      sialosyl Tn, Tn (Golgi region) and sialosyl Lewis(x), and for columnar cells with
      MUC1, Lewis(x), sialosyl Le(x), Tn (cytoplasm) and Lewis(y) (UEA-1). The goblet
      cell spectrum was associated with mucin-like (type I) luminal secretions within
      cancers, whereas the columnar cell spectrum characterized non-mucin-like (type
      II) secretions and intracytoplasmic lumina. These data indicate that colorectal
      cancer mucin can be broadly separated into two types: secretory mucin linked to
      cells of goblet lineage and up-regulated membrane-associated mucin of presumed
      columnar cell origin.

PMID- 9147072
TI  - Co-localization of CD9 and GPIIb-IIIa (alpha IIb beta 3 integrin) on activated
      platelet pseudopods and alpha-granule membranes.
AB  - CD9 is a 24-kDa membrane glycoprotein expressed on the surface of human platelets
      and potentially involved in cellular activation and adhesion functions. This
      protein belongs to a recently delineated family of cell-surface antigens that
      span the membrane four times, called tetraspans, and found mainly in leucocytes
      and tumour cells. As a first approach to clarify the function of CD9, we used
      immunoelectron microscopy to determine the localization of this antigen in human
      platelets, and compared its distribution with that of the GPIIb-IIIa integrin,
      the platelet receptor for fibrinogen. Monoclonal antibodies against CD9 (MAb7)
      and GPIIb-IIIa (HP1-1D) coupled to colloidal gold of different sizes (5 and 15
      nm) were incubated with intact platelets in suspension or on ultrathin sections
      of platelets embedded in LR white. CD9 was found in association with GPIIb-IIIa
      on the inner face of alpha-granule membranes. These two antigens also colocalized
      on pseudopods of activated platelets and in contact regions between adjacent
      platelets. CD63, another member of the tetraspan family, was absent from alpha
      granules but was associated with lysosomal structures. Flow cytometric analysis
      of platelet CD9 with a series of monoclonal antibodies revealed an increased
      expression upon thrombin stimulation, confirming the presence of an intracellular
      granular pool. The observation that CD9 and GPIIb-IIIa are stored in the same
      intracellular structures and migrate to the same activation zones after platelet
      stimulation lends support to previous suggestions of a close association between
      CD9 and GPIIb-IIIa in human platelets and of a possible involvement of CD9 in
      adhesive functions of platelets.

PMID- 9147073
TI  - Light and electron microscopical immunohistochemical localization of large
      proteoglycans in human tooth germs at the bell stage.
AB  - The immunohistochemical localization of large hyaluronate-binding proteoglycans
      has been studied in human tooth germs at the bell stage using a monoclonal
      antibody, 5D5, which is derived from bovine sclera and specifically recognizes
      the core protein of large proteoglycans, such as versican, neurocan and brevican,
      but not that of aggrecan. In the early bell stage before predentine secretion,
      when the enamel organs consisted of the inner and outer enamel epithelia, stratum
      intermedium and stellate reticulum, the enamel organs were not stained by 5D5,
      but the dental papillae and follicles stained strongly. Concomitant with the
      secretion of predentine, dentine and subsequent enamel matrix, strong 5D5
      immunostaining distributed over the entire cell surfaces of secretory ameloblasts
      was observed. The forming enamel matrix showed strong staining. While most of the
      inner and outer enamel epithelia and stratum intermedium lacked staining, the
      cervical loop region and stellate reticulum showed weak staining. Although the
      forming dentine and odontoblasts appeared to lack 5D5 affinity, the predentine,
      dental papilla and dental follicle demonstrated moderate to strong reactivity. At
      the ultrastructural level, specific immunoreaction by immunogold particle
      deposition was clearly detected over the basal lamina of presecretory
      ameloblasts, secretion granules of secretory ameloblasts and the forming enamel
      matrix. These results indicate that a marked increase in the large proteoglycan
      associated with secretory ameloblasts may correlate with cell differentiation and
      enamel matrix biosynthesis.

PMID- 9147074
TI  - Evaluation of immunohistochemical staining of human duodenal endocrine cells
      after microwave antigen retrieval.
AB  - The effect of microwave antigen retrieval on the immunostaining of human duodenal
      endocrine cells in formaldehyde-fixed, paraffin-embedded material was
      investigated. The sections were immunostained by the avidin-biotin complex (ABC)
      and immunogold-silver autometallography (IGSS) methods with and without prior
      microwave treatment. Dilutions of up to 1:30,000 of the following
      antisera/antibodies were used: anti-chromogranin A, anti-chromogranin AB, anti
      secretin, anti-gastrin, anti-gastric inhibitory polypeptide, anti-somatostatin
      and anti-serotonin. The detection threshold for all the antibodies was lower
      after antigen retrieval, and the primary antibody could be used in higher
      dilutions. The dilutions varied for different antibodies and were between two and
      ten times the optimal dilution without antigen retrieval. At extremely high
      dilutions of, or without, the primary antibody, non-specific staining of some
      lymphocytes and the mucus of some goblet cells was observed when the avidin
      method was applied, but not with the immunogold technique. This phenomenon was
      not observed when optimal dilution or a lower dilution was used. This seems to
      have been caused by the binding of the avidin-biotin complex to epitopes in these
      structures unmasked by microwave treatment when competition with specific binding
      sites was absent.

PMID- 9147075
TI  - Incidence of apoptosis in HIV-myelopathy, myelodysplastic syndromes and non
      specific inflammatory lesions of the bone marrow.
AB  - Myelodysplastic syndromes, AIDS-related myelopathy and non-specific inflammatory
      reactions (mostly rheumatoid myelitis) are characterized by normo- to
      hypercellular bone marrow, but frequently display cytopenias in the peripheral
      blood. In the current study we have addressed the question whether this situation
      reflects an increased programmed cell death in haemopoiesis. For this purpose,
      the in situ end-labelling technique was applied to formalin-fixed and paraffin
      embedded trephine biopsies derived from patients and a control group without any
      haematological disorder. Results were evaluated by morphometry. Significantly
      more apoptotic cell death was observed in the haemopoietic marrow of patients
      with either disease. Using double-immunohistochemistry with the monoclonal
      antibody PG-MI (CD68), we were able to demonstrate that approximately one third
      of the apoptotic cells were ingested by macrophages. Our findings are in keeping
      with previously published data that postulated increased frequencies of
      macrophages in these disorders as well as raised serum levels of TNF-alpha.

PMID- 9147076
TI  - Immunohistochemical detection of the Wilms' tumour gene WT1 in desmoplastic small
      round cell tumour.
AB  - The desmoplastic small round cell tumour (DSRCT) is a rare, highly malignant
      neoplasm usually presenting in the abdomen of adolescent males. A characteristic
      translocation between the Ewing's sarcoma gene on chromosome 22 and the Wilms'
      tumour gene WT1 on chromosome 11 has been described, producing a fusion gene with
      expression of the DNA binding area of WT1. Some Wilms' tumour antibodies
      recognize epitopes of this part of the WT1 protein. All four cases of DSRCT
      examined showed strong staining of the tumours with an anti-WT1 antibody,
      suggesting this may be useful in the diagnosis of these tumours.

PMID- 9147077
TI  - G-cell density in the antral mucosa: a feasibility study.
AB  - In this work a new method for gastrin-secreting cell (G-cell) density measurement
      was employed in order to test the hypothesis that G-cell density of the antral
      mucosa can be estimated with an acceptable degree of error. The zone of antral
      mucosa where most G-cells are located was demarcated, its area was measured and
      the G-cells within this area were counted. The variation in the e error of the
      estimate according to normal distribution theory, and the size of the sampling
      expected to yield G-cell density values with a given error were assessed. Our
      data indicate that a very large surface of the G-cell zone should be explored in
      order to estimate G-cell density with an acceptable degree of error. G-cell
      density measurement appears not to be feasible on biopsy specimens or, for
      routine diagnosis, on gastrectomy specimens.

PMID- 9147078
TI  - Melanosis of the appendix: prevalence, distribution and review of the
      pathogenesis of 47 cases.
AB  - The appendix is reported to be a common site for melanosis, especially at autopsy
      although to date there have been few studies expanding or qualifying this
      statement. Based on 47 cases identified from a series of 636 consecutive surgical
      specimens the prevalence, pattern of distribution, nature of the pigment and
      current knowledge of the aetiology and pathogenesis of melanosis of the appendix
      is reviewed and compared with melanosis coli.

PMID- 9147079
TI  - Mucosal prolapse changes in Hirschsprung's disease.
AB  - The aim of this study was to ascertain the incidence of mucosal prolapse changes
      in Hirschsprung's disease. Twenty-three random, consecutive resection specimens
      for this condition were analysed for the histological features of prolapse. Eight
      cases showed histological evidence suggesting mucosal prolapse at the junction
      between ganglionic and aganglionic bowel. Thickening and splaying of the
      muscularis mucosae with extension into the lamina propria, and the presence of
      metaplastic or hyperplastic tubules with goblet cell and cryptal hypertrophy were
      the dominant histological features found in the eight cases. In addition, an
      increase in elastic fibres in the lamina propria and diamond-shaped glands were
      seen to varying degrees in all eight cases. Mucosal prolapse was more prominent
      in the older patients and is, therefore, related to duration of symptoms.
      Differential pressures in ganglionic and aganglionic segments of bowel, together
      with faecal stream and straining are likely to be of pathogenetic significance.

PMID- 9147080
TI  - Histology of aberrant crypt foci in the human colon.
AB  - Aberrant crypt foci (ACF) have been identified in the methylene-blue stained
      mucosa of the human colon. Some lines of evidence suggest that ACF may be
      precursors of colon cancer. The objective of the present study was to establish
      morphological criteria able to define and classify ACF in histological sections.
      Twenty-four colectomy specimens were collected after operation for colorectal
      cancer and fixed in 10% formalin. Strips of grossly normal mucosa were stained in
      a 0.2% solution of methylene blue in saline for 5-10 min. The strips were
      measured, put on a glass slide and observed under a light microscope at x25. One
      hundred and fourteen ACF identified by topology were sectioned parallel to the
      muscularis mucosae. Eighty-four ACF were evident at histological examination and
      could be classified into three main groups: group A (61 ACF, 72.6%) including
      foci whose epithelial cells had regular nuclei, with only mild or focal crowding
      but no stratification, no mucin depletion and no dysplasia; group B (16 ACF,
      19.1%), in which features of hyperplasia were evident; and group C (seven ACF,
      8.3%) including foci with enlarged, crowded and stratified nuclei, mucin
      depletion, frequent mitoses, and evident dysplasia, diffuse or focal (mild in
      five cases, moderate in two) representing microadenomas. Finally, hyperplastic
      foci were significantly larger than foci of group A and C. Group B ACF were also
      more frequent in the rectum than in the colon. In conclusion, selected
      histological features allow the definition of groups of ACF, which may represent
      sequential steps in the development of human colorectal tumours.

PMID- 9147081
TI  - Lesions produced by the extravasation of urine from the upper urinary tract.
AB  - We present six cases which illustrate the spectrum of clinical features,
      macroscopic findings and light microscopic findings of urine extravasation from
      the upper urinary tract. The early lesions are characterized macroscopically by
      an oedematous, glistening or gelatinous appearance to the renal perihilar and
      peripelvic fat. Light microscopically there is lipolysis with associated foamy
      macrophages, multinucleate giant cells and lymphocytes. Immunohistochemical
      staining for Tamm-Horsfall protein is strongly positive in the extracellular
      space and in the foamy macrophages confirming urine extravazation. Later lesions
      are characterized by cicatrization of fibrous tissue around the renal pelvis and
      hydronephrosis. Microscopically there is relatively bland fibrosis with
      occasional lymphocytes and histiocytic cells. The late lesions are also
      characterized by extracellular deposits of weakly eosinophilic, granular or
      hyaline material, the so called 'urinary precipitates'. These deposits stain
      strongly with diastase PAS and weakly positive for Tamm-Horsfall protein. The
      staining of these urinary precipitates is analogous to renal tubular hyaline
      casts, thus supporting the theory that they are derived from uroproteins. We
      consider that these deposits are pathognomic of past urine extravasation.

PMID- 9147082
TI  - Effects of radiation on the normal prostate gland.
AB  - Prostate cancer is one of the commonest tumours of adult males. It shows a range
      of biological behaviour: many tumours are discovered incidentally; others will
      kill by producing widespread metastatic disease. Despite the fact that radiation
      is frequently used in the treatment of a range of pelvic lesions, including
      adenocarcinoma of the prostate itself, studies on the morphological changes in
      the normal prostate gland after irradiation are limited. This seems particularly
      surprising following the increasing use of needle biopsy specimens to assess the
      prostate. Patients who receive pelvic irradiation often suffer from lower urinary
      tract symptoms such as frequency and dysuria and it is possible that these may be
      related to prostatic and/or periprostatic injury. We therefore investigated the
      prostate glands removed at cystoprostatectomy for transitional cell carcinomas of
      the bladder which had received radiotherapy pre-operatively. The changes were
      compared to control prostatic tissue from transurethral resection specimens for
      benign myoadenomatous hyperplasia. We found a range of inflammatory, fibrotic and
      reactive cytological features, including many of the changes seen in benign
      hyperplasia, but these were significantly more exaggerated in the post-radiation
      group. In addition intraprostatic vascular and neural changes were prominent.
      This study documents radiation-induced changes throughout the normal prostate
      gland and neighbouring soft tissue and has particular importance in current
      pathological practice with the increasing and widespread use of needle biopsies
      in the diagnosis and follow-up of prostate cancer.

PMID- 9147083
TI  - Synovial sarcoma of the heart.
AB  - Primary synovial sarcomas of the heart are exceptionally rare tumours, only five
      being previously documented. We report a sixth case and review published data.
      Ages ranged from 13-53 (mean 40.8) years. There were four men and two women who
      characteristically presented with syncope or dyspnoea. Most of the tumours arose
      in the right atrium where they formed pedunculated or polypoid masses. In the
      previously documented cases, all patients died within 9 months. However in our
      case, local excision was felt to have been complete and the patient remains
      disease free at 10 months.

PMID- 9147084
TI  - Erdheim-Chester disease with prominent pulmonary involvement associated with
      eosinophilic granuloma of mandibular bone.
AB  - We report a patient with eosinophilic granuloma localized to the left mandible
      who was subsequently shown to have Erdheim-Chester disease involving the lower
      extremities, omentum and lung. The diagnosis of eosinophilic granuloma was based
      on the presence of typical CD1a+ Langerhans' cell granulomas in a biopsy of
      mandible. The diagnosis of Erdheim-Chester disease was established on the basis
      of the pattern of radioisotopic uptake by long bones, seen on a technetium bone
      scan, and the presence of characteristic histopathological features in biopsies
      of lung and peritoneum. The pathological findings in lung were compatible with
      the abnormalities observed by tomodensitometry, but strikingly different from
      those seen in Langerhans' cell granulomatosis. The differences in the
      histological features of pulmonary involvement seen in the two diseases, and the
      possible relationship between Langerhans' cell granulomatosis and Erdheim-Chester
      disease, are discussed.

PMID- 9147085
TI  - Middle-ear adenoma (MEA): a report of two cases, one with predominant
      "plasmacytoid' features.
AB  - Middle-ear adenomas (MEAs) are rare neoplasms which can display several
      histological patterns and represent a diagnostic challenge. We present two cases
      of MEA which share some histopathological features such as medium to small cells
      forming solid infiltrating tumour nests as well as scattered glandular structures
      with Alcian blue and PAS positive material within. The second case also displayed
      a distinct and predominant "plasmacytoid' appearance which, in a small biopsy,
      might have been misleading. Both cases expressed an admixture of epithelial and
      neuroendocrine immunohistochemical markers, whereas ultrastructural study
      demonstrated electron dense granules. Taken together, these observations support
      a mixed epithelial and neuroendocrine nature for these neoplasms, the
      differential diagnosis of which includes paragangliomas and other tumours or
      tumour-like lesions involving less frequently the middle ear, such as
      meningiomas, plasmacytomas and inflammatory polyps. The existence of MEAs with
      plasmacytoid features should be remembered to avoid confusion with plasmacytomas,
      plasmacytoid myoepithelioma and plasma cell inflammatory infiltrates.

PMID- 9147086
TI  - Solitary fibrous tumour of the thyroid.

PMID- 9147087
TI  - Castleman's disease and lymphoepithelial cysts of the parotid in childhood.

PMID- 9147088
TI  - Pure cartilaginous teratoma differentiated of the testis.

PMID- 9147089
TI  - Primary epithelioid haemangioendothelioma of the peritoneum: an unusual mimic of
      diffuse malignant mesothelioma.

PMID- 9147090
TI  - Mixed olfactory neuroblastoma and craniopharyngioma: an unusual pathological
      finding.

PMID- 9147091
TI  - Spindle and giant cell carcinoma of the colon.

PMID- 9147092
TI  - Disseminated microsporidiosis in a patient with acquired immunodeficiency
      syndrome.

PMID- 9147093
TI  - Dissecting aneurysm of the pulmonary artery associated with a large facial
      cavernous haemangioma.

PMID- 9147094
TI  - Reticuloendothelial haemangioendothelioma.

PMID- 9147095
TI  - T-cell rich alpha-chain disease mimicking T-cell lymphoma.

PMID- 9147096
TI  - Solitary fibrous tumour of the liver.

PMID- 9147097
TI  - Effects of chemotherapy on breast cancer tissue.

PMID- 9147098
TI  - GnRH agonists and uterine leiomyomas.
AB  - Gonadotrophin-releasing hormone (GnRH) agonists are widely used in the treatment
      of women with symptomatic leiomyomas. The effectiveness of this treatment, as far
      as symptoms are concerned, is well established, and in recent years many studies
      have contributed to defining the optimal role for GnRH agonists. Side-effects and
      health risks prohibit the long-term use of these compounds. The combined use of
      high-dose agonists and steroids in the so-called 'add back' schedules reduces
      many of the disadvantages of the monotherapy. However, it is still an expensive
      alternative when compared with definitive surgery, and therefore should only be
      used in women who insist on preservation of the uterus. Low-dose agonist therapy
      ('draw back') has not yet been proven to be suitable for clinical application.
      The use of GnRH agonists and steroids in sequential schedules seems to result in
      a loss of both the volume reduction as well as the reduction in clinical
      symptoms. The use of GnRH agonists prior to myoma surgery should not become a
      routine measure and should be limited to cases where the size of the uterus is >
      600 ml. Hysterectomy should only be preceded by GnRH agonist treatment if uterine
      volume decrease is expected to facilitate either the abdominal or vaginal
      procedure. For both operative procedures the presence of myoma-related anaemia is
      an indication for pretreatment. The use of GnRH agonists before endoscopic
      surgery is widely accepted on the basis of assumptional advantages; however,
      definite proof of these advantages is not yet available.

PMID- 9147099
TI  - Blood flow changes in the uterus induced by treatment with GnRH analogues.

PMID- 9147100
TI  - GnRH analogues in the treatment of uterine fibroids.
AB  - It is now known that gonadotrophin-releasing hormone analogues (GnRHa) are
      extremely efficient at reducing uterine fibroid volume and reversing the related
      symptomatology. However, the fibroids tend to return to their pretreatment size
      about 6 months after discontinuing treatment. GnRHa treatment cannot be continued
      indefinitely due to its potential complications and high cost. It is therefore
      proposed that GnRHa treatment should be phase one of a two-phase treatment plan
      for uterine fibroids. The initial course of GnRHa should be followed by either
      menopause or surgery. Experience with presurgical GnRHa use indicates a definite
      treatment advantage and the use of GnRHa as adjuncts to surgery is well
      established. The value of GnRHa treatment as a alternative to surgery in pre
      menopausal patients, however, remains to be established.

PMID- 9147102
TI  - Theories on the pathogenesis of endometriosis.
AB  - Although endometriosis has been known for over 100 years, its pathogenesis is
      still poorly understood. In this overview the literature regarding the
      pathogenesis of endometriosis is reviewed. The implantation or transplantation
      theory, that suggests implantation and subsequent growth of retrogradely shed
      viable endometrial cells, still remains the most widely accepted theory to
      explain the pathogenesis. The conditions that have to be met for the implantation
      theory are threefold: (i) retrograde menstruation has to occur; (ii) retrograde
      menstruation should contain viable endometrial cells; and (iii) adhesion to the
      peritoneum has to occur with subsequent implantation and proliferation. The
      scientific data to corroborate these conditions will be discussed. A short
      overview is given on cell adhesion molecules, in particular cadherins and
      integrins, the most important cell adhesion molecules involved in cell-cell
      adhesion and cell-extracellular matrix interaction. Special attention is given to
      the possible functional role of these cell adhesion molecules in the pathogenesis
      of endometriosis.

PMID- 9147101
TI  - GnRH agonists: an alternative to surgery?

PMID- 9147103
TI  - Laparoscopic treatment of symptomatic endometriosis.
AB  - From their experience and from data in the literature, the authors try to define
      the respective place of the different treatments for endometriosis, especially
      those of operative laparoscopy. In cases of endometriosis-associated infertility,
      operative laparoscopy is the first line treatment and assisted reproductive
      technology (ART) the second one. Gonadotrophin-releasing hormone (GnRH) analogues
      are only useful in cases of extensive endometriosis to render surgery easier, and
      for ART. The average pregnancy rate following laparoscopic treatment is
      approximately 50% (range 34-80%). It is poorly related to the type of
      endometriosis except in cases of large adhesions and tubal involvement. However,
      duration of infertility, age and sperm quality have a direct influence on it.
      Therefore the authors propose a scheme for the management of endometriosis
      associated infertility. In cases of pain, laparoscopic surgery can also be used;
      however, drugs have a more important role in these cases, to avoid recurrent
      surgery.

PMID- 9147104
TI  - Medical treatment of symptomatic endometriosis.
AB  - The concept of endometriosis and strategies for its treatment are reviewed.
      Treatment is mainly endocrine-based, using progestogens, danazol and luteinizing
      hormone-releasing hormone (LHRH) agonists. Such treatment is complex, and therapy
      strategies have to be tailored to the individual; the choice of treatment,
      therefore, depends on the metabolic and side-effects of each compound.

PMID- 9147105
TI  - The relevance of asymptomatic endometriosis.
AB  - Asymptomatic endometriosis is likely to be a physiological phenomenon of very
      limited relevance to both the physician and the patient. The evolution of our
      understanding of this phenomenon is a parable for modern medicine. It is likely
      that access to a new diagnostic technique, a powerful armoury of medical and
      surgical treatments and the necessity for doctors to feel they are doing
      something positive for the patient, have created an incorrect disease model for
      asymptomatic endometriosis. As responsible clinicians and medical scientists it
      behoves us to honestly re-examine our approach to this phenomenon.

PMID- 9147106
TI  - Roles of follicle stimulating hormone and luteinizing hormone in controlled
      ovarian hyperstimulation.

PMID- 9147107
TI  - Role of different GnRH agonist regimens in pituitary suppression and the outcome
      of controlled ovarian hyperstimulation.
AB  - Gonadotrophin-releasing hormone (GnRH) agonists have become irreplaceable
      addition to gonadotrophins in ovulation induction for assisted reproduction. Of
      the several schemes currently employed, long regimens appear to be maximally
      effective to optimize patient scheduling and to improve clinical results.

PMID- 9147108
TI  - Dose relationship between GnRH antagonists and pituitary suppression.
AB  - While the clinical significance of gonadotrophin-releasing hormone (GnRH)
      agonists is well recognized, the potential use of GnRH antagonists in humans
      awaits the availability of potent analogues with no untoward side-effects. We
      have designed, synthesized and tested several hundred linear and cyclic analogues
      (agonists and antagonists) of GnRH in different rat models; some have high
      histamine releasing activity and others have poor solubility in aqueous buffers
      with a pH > 6.0. Furthermore, we have identified analogues exhibiting short (< 12
      h), intermediate (12-72 h) and long (> 72 h) duration of action in the rat (50
      micrograms s.c. dose/rat). We have concluded that the basis for such resistance
      to degradation and elimination must be specific. In order to gain further
      information on the optimal nature and sterical requirements of side-chains,
      preliminary experiments were carried out using betidamino acids. Finally, mono-
      and dicyclic analogues of GnRH with potencies comparable with that of the most
      potent linear analogues were also obtained. Our approach to the development of
      such analogues included the use of nuclear magnetic resonance and computational
      techniques as well as that of state-of-the-art synthetic approaches. We intend to
      use the information derived from these structure/activity relationship studies to
      design conformationally-similar peptido-mimetics.

PMID- 9147109
TI  - Cytogenetics of infertile men.
AB  - Chromosomally derived sterility has long been recognized. A review of the
      literature of somatic chromosome investigations in infertile males has shown that
      13.7% of azoospermic males and 4.6% of oligozoospermic males have an abnormal
      karyotype. In the first group, sex chromosome abnormalities predominate (mainly
      47,XXY), whereas in the latter, autosome anomalies (i.e. Robertsonian and
      reciprocal translocations) are the most frequent. A similar review on meiotic
      studies revealed that meiotic chromosome anomalies can explain male infertility
      in 4.3-40.4% of patients. Recently, fluorescent in-situ hybridization studies on
      spermatozoa from infertile men were published; it was suggested that both X-Y
      pairing and pairing of the autosomes were impaired, resulting in spermatogenic
      disruption. We investigated cytogenetically 694 infertile men with abnormal sperm
      parameters. More patients are needed for this research to investigate the
      relationship, if any, between the type of chromosome abnormality and its
      influence on the number, morphology and motility of spermatozoa. To be able to
      provide proper counselling for those couples whose male infertility can now be
      treated by intracytoplasmic sperm injection, it is suggested that clinical
      investigations should include mitotic and meiotic studies, an analysis of the
      chromosome content of individual spermatozoa and a DNA analysis of blood and
      spermatozoa to detect partially deleted Y chromosome material.

PMID- 9147111
TI  - Cystic fibrosis and infertility caused by congenital bilateral absence of the vas
      deferens and related clinical entities.
AB  - The condition of congenital bilateral absence of the vas deferens (CBAVD) is, in
      the majority of patients, related to defects in the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene. CBAVD patients either are compound
      heterozygotes (carrying different mutations in their two CFTR genes) or carry a
      mutation in one of their CFTR genes and an intron 8 5T splice variant, associated
      with low levels of functional CFTR protein, in their second gene. The
      relationship between cystic fibrosis (CF) and CBAVD requires a proper clinical
      examination of the patient, a CFTR mutation analysis for himself and his family
      and genetic counselling. A mutation analysis should also be performed for the
      wives of CBAVD males because such couples now have the possibility of having
      their own genetic children but are at increased risk of having children with CF
      and/or CBAVD. The aetiology of some conditions of CBAVD is not related to CF,
      especially when CBAVD is associated with urinary tract malformations (up to 20%
      of cases). In couples with CBAVD not related to CF there is no increased risk of
      CF children, but it is not known whether they have an increased risk of having
      sons with CBAVD. In some of the patients with congenital unilateral absence of
      the vas deferens (CUAVD) the condition is also related to CF, especially in cases
      where there is an occlusion of the palpable vas. The CFTR gene is probably not
      involved in the aetiology of Young's syndrome. Follow-up studies of children born
      to couples where the males have CBAVD, CUAVD or Young's syndrome are mandatory
      and will help to better define the risk to their offspring of CF and/or of
      inheriting their paternal infertility condition.

PMID- 9147112
TI  - Registration of congenital anomalies in ART populations: pitfalls.
AB  - Various methodological pitfalls preclude simple validation of the ostensible
      safety of offspring conceived thorough assisted reproductive technologies (ART).
      These pitfalls include lack of an appropriate comparison group (control), failure
      to take into account potential confounding variables, anomaly surveillance that
      is either too rigorous or too lax compared to the way in which anomalies are
      sought in general population surveys, and inconsistent criteria with respect to
      classifying anomalies (inclusion or exclusion of minor anomalies, internal
      anomalies evident only on ultrasound, and anomalies present in terminated
      pregnancies). To minimise these pitfalls, we recommend prospective surveillance
      for major anomalies, best defined as defects resulting in death, causing major
      handicap or necessitating surgery. Surveillance should ideally begin as soon as
      pregnancy is diagnosed. Data should be gathered allowing potential confounding
      variables to be taken into account, and systematic neonatal surveillance for
      anomalies should be performed during a designated time interval.

PMID- 9147113
TI  - Registers of in-vitro fertilization and assisted conception.
AB  - Many countries now have registers of assisted conception that were initially set
      up to evaluate the effectiveness of treatment, to monitor pregnancy outcomes and
      the health of treated women, and to assess any immediate risks for the women and
      their children. World reports, based on information from national registers, have
      enabled international comparisons of the extent to which the various techniques
      of assisted conception are used to treat infertile couples, as well as
      comparisons of pregnancy outcome. The reports also provide comparative data on
      pregnancy rates in populations rather than in single in-vitro fertilization (IVF)
      centres. To determine whether newly introduced techniques such as
      intracytoplasmic sperm injection are associated with any increased risks of birth
      defects or other adverse outcomes, information notified to registers will often
      need to be supplemented by clinical reports or by linkage of data in IVF
      registers and other health data systems. Further efforts to improve the quality
      of information on assisted conception within each country and internationally
      need to be well supported so that the effectiveness of treatment and the outcomes
      of treated couples and their children can be evaluated properly.

PMID- 9147114
TI  - The outcome of multiple pregnancy.
AB  - The incidence of multiple pregnancy and delivery has increased dramatically over
      the past 10-15 years in many developed countries of the world. Data for England
      and Wales show that between 1980 and 1993 the twin maternity rate increased by
      approximately 25% and the triplet and higher order maternity rate more than
      doubled. Similar trends have been reported elsewhere. The majority of these
      increases have been linked to the use of ovarian stimulants and assisted
      reproduction techniques, and multiple pregnancy must be considered to be one of
      the most important adverse outcomes in current methods of infertility treatment.
      Obstetric complications associated with multiple pregnancy include prenatal
      screening problems and increased incidence of pregnancy-induced hypertension,
      antepartum haemorrhage, preterm labour and assisted or surgical delivery.
      Neonatal problems include low birthweight and increased prevalence of congenital
      malformations. Compared with singletons, neonatal mortality was seven times
      higher in twins and > 20 times higher in triplets and higher order births in
      England and Wales in 1991. Survivors also suffer higher rates of cerebral palsy
      and other neurological impairments. Most studies of pregnancies and babies
      resulting from assisted reproduction have demonstrated similar, if not higher,
      risks of adverse obstetric and neonatal outcomes for multiple births compared
      with national expectations. A poorer outcome in multiple pregnancy, especially in
      triplet and higher order pregnancy, supports the replacement of two good quality
      embryos in assisted reproduction treatment cycles.

PMID- 9147115
TI  - Obstetric outcome of 904 pregnancies after intracytoplasmic sperm injection.
AB  - The obstetric data of 904 consecutive pregnancies obtained after intracytoplasmic
      sperm injection (ICSI) using ejaculated spermatozoa (group I), epididymal
      spermatozoa (group II), testicular spermatozoa (group III) and after the
      replacement of frozen-thawed embryos (group IV) are described. In all, there were
      785 pregnancies in group I, 37 pregnancies in group II, 30 pregnancies in group
      III and 52 pregnancies in group IV. A total of 24 pregnancies (2.5%) have so far
      been lost to follow-up. The incidence of pregnancy loss, i.e. subclinical
      pregnancies, clinical abortions and ectopic pregnancies were highest in group IV
      (61.4%). Early pregnancy loss in groups I, II and III were 21.9, 37.8 and 33.3%
      respectively. Prenatal diagnosis was performed in 64.4% of the clinical
      pregnancies: amniocentesis in 48.2% and chorionic villus sampling in 16.2%. The
      karyotypes were normal in 97.6% of the prenatal diagnoses and there were 1.2% de
      novo and 1.2% inherited chromosome aberrations. Pregnancy complications such as
      prematurity and low birthweight were related to pregnancy multiplicity. Perinatal
      mortality occurred in 15 babies (17.1 per thousand), including nine intrauterine
      fetal deaths after 25 weeks of gestation and six cases of mortality during the
      first 7 days after birth. There is no evidence that the technique of ICSI using
      sperm cells of different origins yielded a higher obstetric risk.

PMID- 9147116
TI  - Prospective follow-up study of 877 children born after intracytoplasmic sperm
      injection (ICSI), with ejaculated epididymal and testicular spermatozoa and after
      replacement of cryopreserved embryos obtained after ICSI.
AB  - A prospective follow-up study of 877 children born after ICSI was carried out.
      The aim of this study was to compile data on karyotypes, congenital
      malformations, growth parameters and developmental milestones so as to evaluate
      the safety of this new technique. The follow-up study included agreement to
      genetic counselling and prenatal diagnosis and was based on a physical
      examination at the Centre for Medical Genetics (Dutch-speaking Brussels Free
      University, Brussels, Belgium) at 2 months, 1 year and 2 years, when major and
      minor malformations and a psychomotor evolution were recorded. Between April 1991
      and July 1995, 904 pregnancies obtained after intracytoplasmic sperm injection
      (ICSI) led to the birth of 877 children (465 singletons, 379 twins and 33
      triplets). Prenatal diagnosis determined a total of 486 karyotypes, of which six
      were abnormal (1.2%) and six (1.2%) were familial structural aberrations, all
      transmitted from the father. This slight increase in de-novo chromosomal
      aberrations and the higher frequency of transmitted chromosomal aberrations are
      probably linked directly to the characteristics of the infertile men treated
      rather than to the ICSI procedure itself. In all, 23 (2.6%) major malformations
      were observed in the children born, defined as those causing functional
      impairment or requiring surgical correction. No particular malformation was
      disproportionately frequent. Compared with most registers of children born after
      assisted reproduction and with registers of malformation in the general
      population, the figure of 2.6% was within the expected range. These observations
      should be further completed by others and by collaborative efforts. In the
      meantime, patiens should be counselled about the available data before any
      treatment: the risk of transmitted chromosomal aberrations, the risk of de-novo,
      mainly sex chromosomal, aberrations and the risk of transmitting fertility
      problems to the offspring. Patients should also be reassured that there seems to
      be no higher incidence of congenital malformations in children born after ICSI.

PMID- 9147117
TI  - Report on the activities of the ESHRE Task Force on intracytoplasmic sperm
      injection. European Society of Human Reproduction and Embryology.
AB  - The application of intracytoplasmic sperm injection (ICSI) is rapidly becoming
      more popular around the world. The European Society of Human Reproduction and
      Embryology (ESHRE) Task Force is aiming to collect annually the clinical results
      and the pregnancy outcomes of ICSI using ejaculated, epididymal and testicular
      spermatozoa to enable the provision of reliable information on the efficacy and
      safety of this novel technique. This review summarizes the activities of the
      ESHRE Task Force on ICSI during the last 2 years. The number of centres
      performing ICSI as well as the number of ICSI cycles increased significantly from
      1993 to 1994. The incidence of oocytes damaged by the procedure was low (7.2
      10.6%), whereas the fertilization rate achieved with ejaculated, epididymal and
      testicular spermatozoa was high (51.1-60.8%), even with extremely impaired semen
      quality. Thus, 89-93% of patients had an embryo transfer and 21-31% of them
      achieved a viable pregnancy, irrespective of the origin of the spermatozoon. ICSI
      results were similar in 1993 and 1994. The follow-up of children born after ICSI
      revealed no increase in the incidence of major congenital malformations or
      chromosomal aberrations. These findings are quite reassuring, although the
      numbers are still too few. Therefore, efforts need to be continued to enhance the
      database and thus provide a reliable assessment of this new treatment modality.

PMID- 9147118
TI  - The special needs patient. Treatment in general dental practice: is it feasible?
AB  - Special needs patients often have difficulty in obtaining dental treatment. This
      paper highlights these problems and discusses, specifically, how these problems
      relate to the special needs patient in Hong Kong.

PMID- 9147119
TI  - Dental anxiety among Australians.
AB  - This study aimed to estimate the prevalence of dental anxiety and examine its
      associations among a representative sample of Australians aged 18 and over. A
      random sub-sample of participants in a national dental telephone interview survey
      completed a follow-up postal questionnaire (response rate 85.2 per cent) which
      included Corah's Dental Anxiety Scale (DAS). The prevalence of dental anxiety
      (defined by a DAS score of 13 or more) in the sample was 14.9 per cent, with
      overall severity represented by the mean score of 9.04 (sd, 3.45). The prevalence
      and severity of dental anxiety were greater among women than men, and in the 35
      44 age group. High-anxiety individuals reported more deferring of dental care,
      and more frequently reported an episodic dental visiting pattern. Although there
      were no differences in dental anxiety by self-reported dental status, individuals
      who reported impact from their oral conditions had higher dental anxiety. These
      associations with social impacts and deferment of care indicate that dental
      anxiety may be an important dental public health problem in Australia.

PMID- 9147120
TI  - The community care model of the Intercountry Centre for Oral Health at Chiangmai,
      Thailand.
AB  - The Intercountry Centre for Oral Health opened in Chiangmai, Thailand, in
      November, 1981. In 1984, as part of its mandate to promote new approaches to the
      delivery of oral health care, it initiated a demonstration project known as the
      Community Care Model for Oral Health. Logistic, financial and organisational
      difficulties prevented the full implementation of the original plan.
      Nevertheless, consideration of the strengths and weaknesses of the Model has
      provided valuable suggestions for adoption by national and international health
      agencies interested in adopting a primary health care approach to the delivery of
      oral health services. Important features which could be appropriate for
      disadvantaged communities include: integration into the existing health service
      infrastructure; emphasis on health promotion and prevention; minimal clinical
      interventions; an in-built monitoring and evaluation system based on
      epidemiological principles, full community participation in planning and
      implementation; the establishment of specific targets and goals; the instruction
      of all health personnel, teachers and senior students in the basic principles of
      the recognition, prevention and control of oral diseases and conditions; the
      application of relevant principles of Performance Logic to training; and the
      provision of a clear career path for all health personnel.

PMID- 9147121
TI  - Evaluation of health care workers' accuracy in recognising oral cancer and pre
      cancer.
AB  - The aim of the study was to evaluate dental health care workers' ability to
      recognise oral cancer and pre-cancer from colour photographic slides. A set of 80
      slides was prepared, 40 were negative (normal mucosa or lesions with no malignant
      potential) and 40 were positive (cancer or potentially malignant lesions). The
      slides were arranged in random order and projected in a standard format. The
      performance was evaluated in terms of mean sensitivity, specificity, mean correct
      score and likelihood ratio. There were no significant differences between the
      three groups of dentists (consultants, juniors hospital dentists and general
      dentists), all performed better than the auxiliaries. The chances of a consultant
      making a correct decision were 5.5 times better than for an auxiliary and 2.7
      times better than for a junior hospital dentist. The slide show enables a
      comparison of health care workers to be made and may be useful for the
      evaluation, training and calibration of examiners for an oral cancer screening
      programme.

PMID- 9147122
TI  - The effectiveness of an amine fluoride/stannous fluoride dentifrice on the
      gingival health of teenagers: results after six months.
AB  - The objectives of the present study included examining the effect of non
      supervised tooth brushing with an amine fluoride/stannous fluoride (AmF/SnF2)
      dentifrice on gingival health of teenagers in a field trial over six months.
      Jerusalem high-school adolescents (246) participated in a double-blind study with
      a NaF dentifrice serving as control. No oral hygiene instruction or supervision
      was given. Examinations took place at baseline, three weeks, three months and six
      months. In all examinations, no differences were revealed for plaque levels.
      Other results indicated a consistent advantage for the AmF/SnF2 group. Gingival
      Index (GI) scores were significantly lower in the test group at the three month
      examination (GI = 0.85, compared to GI = 0.89; p = 0.036) and at the six month
      examination (GI = 0.72, compared to 0.78; p = 0.042) than among controls. Mean
      bleeding on probing scores were lower in the AmF/SnF2 than in the control group
      at the six month examination (0.53, compared to 0.63; p = 0.041). No side
      effects, including staining, were reported, nor found, among the AmF/SnF2 group.
      In addition to the well established caries preventive role of fluoride
      dentifrice, these data indicate an additional and important public health role of
      a AmF/SnF2 dentifrice, in preventing gingivitis.

PMID- 9147123
TI  - Variations in plaque scores in a small group of individuals over a four week time
      period.
AB  - Individual plaque scores were assessed in a group of individuals over a four week
      period and compared to the group mean value for the group. No instruction in
      toothbrushing or professional prophylaxis was undertaken during the period of
      study. While the mean values for the group remained virtually unchanged
      throughout the course of the study, the levels of plaque varied considerably
      between individuals over the period of investigation. Thus it is concluded that
      the use of plaque scores in clinical practice may not adequately reflect the true
      relevance of dental plaque and its role in the initiation and progression of
      gingival inflammation in individuals. Furthermore, pooling of data from clinical
      trials masks the wide variations and changes in plaque scores in individual
      subjects which may adversely affect the conclusions drawn from the statistical
      analysis of the data.

PMID- 9147125
TI  - Analysis of fluoride ion concentrations and in vitro fluoride uptake from
      different commercial dentifrices.
AB  - The effectiveness of fluoride (F) dentifrices in reducing dental caries is well
      documented. However, not all F dentifrices are equally effective. The objective
      of this study was to compare fluoride uptake from Thai, Chinese and Indian
      dentifrices which are widely used in these respective countries. A non-fluoride
      dentifrice was included as a control. Dentifrices were analysed for fluoride
      concentrations using the 'acid-etch biopsy technique'. This study suggests that,
      when compared to 'multinational dentifrices', the Thai, Chinese and Indian
      dentifrices manufactured locally failed to show the F availability and/or F
      uptake efficacy even though they claimed to contain varying levels of F.

PMID- 9147124
TI  - The effect of areca nut on salivary and selected oral microorganisms.
AB  - The aim of this study was to investigate the effect on the growth of salivary and
      selected oral microorganisms of areca nut, aqueous extracts of the nut, its major
      alkaloid arecoline and the components tannic acid and catechin of its tannin
      fraction. The antibacterial properties of the above were tested on Streptococcus
      mutans, Streptococcus salivarius, Candida albicans and Fusobacterium nucleatum
      and, as a control, Staphylococcus aureus. This was followed by investigating its
      effect on salivary organisms cultured from the saliva after chewing boiled areca
      nut. Extracts inhibited the growth of the selected organisms in a concentration
      dependent manner, baked and boiled nuts being significantly more potent than raw
      nut. Growth of C. albicans was the least affected by the nut extracts. Tannic
      acid was strongly antibacterial but not catechin or arecoline. No antibacterial
      effect could be demonstrated on salivary organisms after chewing the nut for 5
      minutes but exposure of saliva to the cud for 1 hour caused a significant
      depression of bacterial growth. It is concluded that the hydrolysable tannins in
      the tannin fraction, which include tannic acid, are responsible for the
      antibacterial properties of the nut and that prolonged intraoral exposure to the
      nut can suppress bacteria in the mouth.

PMID- 9147126
TI  - Temperature change in the pulp chamber during application of heat to composite
      and amalgam cores and its returning time to oral heat.
AB  - Protection of vital tissue, especially pulp tissue, is essential to any
      restorative dental procedure. This study observed the temperature changes in the
      pulp chamber one minute after application of heat of different degrees to
      composite and amalgam cores and period of time necessary for the temperature
      measured in the pulp one minute after heat application to return to 36 degrees C.
      For this, twelve extracted, morphologically intact human teeth were chosen. Four
      pins were placed in each of the teeth. Amalgam and composite cores were prepared.
      All specimens were placed in a water bath at 36 degrees C. Heat of 0 degree C, 40
      degrees C, 60 degrees C, 80 degrees C was applied to the cores on the teeth and
      the temperature of the pulp was measured one minute later by means of a
      thermocouple. For both amalgam and composite cores, the lowest increase in the
      pulp temperature was established after the 40 degrees C heat application.

PMID- 9147127
TI  - Stomatin.
AB  - Stomatin is a 31-kDa integral membrane protein, named after the rare human
      haemolytic anaemia hereditary stomatocytosis. In some cases of this anaemia, in
      which the red cells leak sodium and potassium ions, this protein is absent from
      the membrane, immediately suggesting that it has a role in the regulation of ion
      transport. The protein has a single hydrophobic domain, presumed to be membrane
      associated, is phosphorylated, and is widely distributed in animal tissues.
      Mutations of a homologue in sensory nerve cells of the nematode Caenorhabditis
      elegans disrupt a neuronal transduction mechanism, in which mechanosensory
      information is relayed to an ion channel, whose opening initiates an action
      potential. It could be that this protein is a molecular link in a genetic stretch
      sensitive system. Abnormalities of red cell ion transport are well known in human
      hypertension, but the molecular basis has never been elucidated: this protein and
      its functional associates, operating in a stretch- or pressure-sensitive complex,
      might be important.

PMID- 9147128
TI  - Retinoid X receptors.
AB  - Retinoids are metabolites of retinol (vitamin A), which act as signalling
      molecules in embryogenesis and as stimulators of cellular differentiation. The
      potency of retinoids as differentiating agents has led to their successful use in
      treating skin diseases and some forms of cancer. The retinoid X receptors (RXRs)
      are receptors for the vitamin A metabolite 9-cis retinoic acid, and they are
      members of the steroid/thyroid hormone receptor superfamily of DNA binding
      nuclear hormone receptor. The RXRs are also cofactors required for transcription
      activated by some other members of the steroid/thyroid hormone receptor
      superfamily, including the all-trans retinoic acid, thyroid hormone, vitamin D
      and peroxisome proliferator-activated receptors. The biological importance of the
      RXRs has been demonstrated in recent genetic studies which have shown that some
      RXR null mutations in mice have phenotypic effects similar to vitamin A
      deficiency.

PMID- 9147129
TI  - Structural, catalytic, and functional properties of low M(r), phosphotyrosine
      protein phosphatases. Evidence of a long evolutionary history.
AB  - The PTPase family comprises a number of classes of functionally and structurally
      unrelated enzymes; it represents an important component of the protein-tyrosine
      phosphorylation/dephosphorylation machinery, which regulates the level of
      tyrosine phosphorylation of a number of intracellular proteins. A wealth of
      recently reported data indicates growing interest in a group of PTPases
      characterized by low (near 20 kDa) molecular weight and high sequence homology
      (low M(r), PTPases). These enzymes are present in organisms spanning the
      philogenetic scale, from prokaryotes to yeast and mammals. The sequence homology
      of the low M(r), PTPases with other classes of PTPases is limited to the active
      site sequence CXXXXXRS/T, containing the Cys and Arg residues involved in enzyme
      catalysis found in all PTPases. The X-ray structural data of three enzymes
      belonging to different classes of PTPases, a bovine liver low M(r), PTPase
      isoenzyme, PTP1B, and Yersinia PTPase, show that all these enzymes maintain the
      same active site and overall catalytic mechanism, though displaying different
      chain foldings and topologies, supporting convergent evolution. Limited findings
      on the in vivo function of the low M(r), PTPases are presently available;
      however, an involvement of the mammalian enzymes in the membrane growth factor
      receptor signal transduction is emerging. The distribution of these enzymes in
      philogenetically distant unicellular and multicellular organisms supports their
      participation in important cell functions.

PMID- 9147130
TI  - ADP-ribosylated actin as part of the actin monomer pool in rat brain.
AB  - Mono-ADP-ribosylation in mammals is poorly understood. In this study, we found
      mono-ADP-ribosylated actin in rat brains. Mono-ADP-ribosylated actin by ADP
      ribosyltransferase or nonenzymatic reaction was shown at a different position
      from the unmodified actin in the isoelectrical focusing. High-pressure liquid
      chromatography utilizing a reverse phase (ODS) column separated ADP-ribosylated
      actin from unmodified actin. In the two-dimensional gel electrophoreses and high
      pressure liquid chromatography, the endogenously ADP-ribosylated actin was
      detected in the supernatant fraction from the rat brain extract, where a
      nonpolymerizing actin was present after removal of the polymerizing actin. The
      concentration of NAD and ADP-ribose, after microwave irradiation, was 220 nmol
      and 150 nmol/g of rat brain tissue. Actin ADP-ribosylated by purified ADP
      ribosyltransferase failed to form actin filaments after the addition of Mg2+.
      Actin ADP-ribosylated by the nonenzymatic reaction could polymerize with the
      addition of Mg2+. The enzymatically modified actin could form actin filaments
      after treatment with ADP-ribosylhydrolase but not after treatment with
      phosphodiesterase. These results suggest that ADP-ribosylated actin by enzymatic
      or nonenzymatic reaction is one of the sequestering factors in actin-actin
      binding and is a part of the actin pool in the rat brain.

PMID- 9147131
TI  - Some properties of inorganic pyrophosphatase from Bacillus subtilis.
AB  - Inorganic pyrophosphatase (pyrophosphate phosphohydrolase, EC 3.6.1.1; PPase)
      from Bacillus subtilis was purified to a homogeneous state electrophoretically
      when analysed by SDS-PAGE. The enzyme consists of six identical subunits; the
      molecular weight of the native enzyme estimated by gel filtration was approx.
      120,000, and denaturing polyacrylamide gel electrophoresis gave a single band
      corresponding to 24,000. The enzyme absolutely required a divalent cation for its
      activity. Mg2+ was most effective, showing two steps of concentration-dependent
      activation. Mg2+ could be partially replaced by Mn2+ and Co2+. The enzyme was
      thermostable in the presence of Mg2+, and no loss of activity was observed on the
      incubation at 55 degrees C for an hour.

PMID- 9147132
TI  - Changes in the C-terminal region of alpha-A crystallin during human
      cataractogenesis.
AB  - Reverse phase chromatography was used to purify alpha-A crystallin from total
      protein of human cataractous and normal lenses, followed by tryptic digestion and
      quantitation of the peptides corresponding to the intact C-terminal region of the
      protein. Relative to alpha-A crystallin from normal lenses, alpha-A crystallin
      from cataractous lenses contained decreased amounts of the expected C-terminal
      tryptic peptides. In an alternative approach, antiserum specific for the C
      terminal region of the protein was used to quantitatively probe Western blots of
      total proteins from cataractous and normal lenses. The results demonstrated a
      decrease in the amount of this antiserum binding to the C-terminal region of
      alpha-A crystallin from human cataracts. Together, these studies show that
      relative to alpha-A crystallin from normal lenses, there is a decrease in the
      amount of the intact C-terminal region during the process of human
      cataractogenesis.

PMID- 9147133
TI  - Molecular cloning of diadenosine tetraphosphatase from pig small intestinal
      mucosa and identification of sequence blocks common to diadenosine polyphosphate
      hydrolases and phosphorylases.
AB  - Diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A) pyrophosphohydrolase is the enzyme
      responsible for reducing intracellular levels of the stress-responsive nucleotide
      diadenosine 5',5"'-P1,P4-tetraphosphate. In order to gain more information on the
      relationships between the enzymes hydrolysing diadenosine polyphosphates in
      different eukaryotes, the Ap4A hydrolase and a corresponding cDNA have been
      isolated from pig small intestinal mucosa by standard procedures. The enzyme is a
      typical mammalian Ap4A hydrolase (Km = 0.8 microM) being sensitive to inhibition
      by fluoride (Ki = 24 microM) and adenosine 5'-tetraphosphate (Ki = 10 nM) and
      yielding ATP and AMP as products. A low Km Ap4A hydrolase (Km = 0.3 microM) was
      also isolated from rabbit small intestinal mucosa. These enzymes differ from the
      rat intestinal mucosal hydrolase, which has much higher values of Km for Ap4A and
      Ki for adenosine 5'-tetraphosphate. A cDNA encoding the pig enzyme was isolated
      from a pig ileum cDNA library. The derived amino acid sequence of the 16.8 kDa
      gene product shows 88% identity and 96% similarity to that of the human enzyme.
      The sequence has the same modification of the MutT motif found in the human
      enzyme in which a threonine residue replaces a hydrophobic amino acid. Sequences
      comparisons among eukaryotic diadenosine polyphosphate hydrolases and
      phosphorylases reveal two blocks of amino acid similarity, including a motif,
      Z[AD]Gx[ED]AGQ, which may be involved in polyphosphate binding by the hydrolases,
      and an invariant histidine residue that may be involved in catalysis. These
      sequence similarities may have arisen by convergent evolution.

PMID- 9147134
TI  - Molecular modelling studies of lysozyme catalysed hydrolysis of synthetic
      substrates.
AB  - Kinetic data for the lysozyme catalysed hydrolysis of aryl chitooligosides were
      surveyed. Both electron-donating and electron-withdrawing substituents on the
      departing aryl aglycones enhance the rate of hydrolyses. The parallel pH-rate
      profiles implicate that identical catalytic residues are involved in the
      hydrolytic fission of the glycosyl-aryloxy bond of these two groups of synthetic
      substrates. Molecular modelling studies of lysozyme complexes with aryl diN
      acetyl chitobiosides and their intermediates were performed. The two synthetic
      substrates bearing aryl aglycones with opposite electronic effects bind to the
      active site of lysozyme in different conformations. Based on the energetic and
      geometric considerations, the oxocarbonium ion whose pyranose ring D in a sofa
      conformation is the most plausible reaction intermediate for the lysozyme
      catalysed hydrolysis of the synthetic substrates. The modelling study also
      suggests that considerable conformational changes of both the lysozyme binding
      site and the chitobiosyl group accompany the formation of the glycosyl enzyme
      intermediate. In particular, the chitobiosyl group undergoes a dislocation of the
      pyranose ring C from the subsite C and a constraint of the pyranose ring D to
      form a boat conformer.

PMID- 9147135
TI  - Time course of hexachlorobenzene-induced alterations of lipid metabolism and
      their relation to porphyria.
AB  - A great deal of information concerning the effects of hexachlorobenzene on the
      haem metabolic pathway has been obtained but little is known about the effects of
      the drug on lipid metabolism. Consequently, the time course of phospholipid
      metabolism alteration caused by this xenobiotic was evaluated as related to
      changes in porphyrin metabolism with the aim to understand better the
      interregulation of both metabolisms. Female Wistar rats were treated with HCB (1
      g/kg) over a 1-8 week period. Individual phospholipid content, [32P]
      incorporation, total lipid content, lipid peroxidation, uroporphyrinogen
      decarboxylase activity, its inhibitor generation and porphyrin content, were the
      parameters measured in the liver of treated rats. Phospholipid metabolism-with
      the exception of sphingomyelin-presents a biphasic behaviour, in both the
      endogenous contents and de novo synthesis. The turning point between both phases
      is the time at which levels of porphyrin and conjugated dienes increase, the
      latter compounds being involved in oxidative processes. On the other hand,
      sphingomyelin decreases continuously during the 8 weeks of treatment. It was also
      found that the malondialdehyde content increased during the early stages. The
      time sequence for haem metabolism parameters showed that the accumulation of
      porphyrins occurs after the decrease in uroporphyrinogen decarboxylase activity
      and the enzyme inhibitor formation, which are early events (first and second
      weeks). Porphyrins could not by themselves exacerbate uroporphyrinogen
      decarboxylase impairment or inhibitor generation. This study shows that
      hexachlorobenzene alters simultaneously phospholipid and porphyrin metabolisms
      from the early stages, and generates an oxidative environment that favours
      porphyrinogens and lipid oxidation at later stages. So, this oxidative
      environment links the alterations on both metabolisms.

PMID- 9147137
TI  - Hydrophobic interactions are involved in the inhibition of human leukocyte
      elastase by alkyltrimethylammonium salts.
AB  - Electrostatic forces and hydrophobic interactions had been suggested to modify
      the adsorption of elastases onto insoluble fibrous elastin, which is the initial
      stage of elastolysis, but conflicting results had been obtained, and comparison
      between compounds with different structures was difficult. In order to explore
      these observations, we have studied the effect of six alkyltrimethylammonium
      bromides, with alkyl chain length ranging from six to 16 carbon atoms, on human
      leucocyte elastase activities, either with a synthetic substrate or with
      insoluble elastin. The enzymatic studies were performed either
      spectrophotometrically or using conductimetry, and direct binding on to elastin
      was conductimetrically measured. Binding of the alkyltrimethylammonium salts is
      increasing with alkyl chain length and we could demonstrate a cooperative binding
      for tetra- and hexadecyl chains. No effect of the six compounds could be
      evidenced on hydrolysis of a specific synthetic substrate. With insoluble
      elastin, elastolysis inhibition could be demonstrated for alkyl chain longer than
      ten carbon atoms, the effect increasing with chain length. A similar inhibition
      was observed with the soluble kappa-elastin, but it was less effective. The study
      shows that the interaction between the alkyltrimethylammonium salts and elastin
      plays a major role in the inhibitory potency of these molecules. As this effect
      is enhanced with alkyl chain length, it was concluded that hydrophobic
      interactions favour their binding, protecting elastin against elastase
      adsorption.

PMID- 9147136
TI  - Purification of aminopeptidase from Australian classified barley flour.
AB  - Barley is one of the major crops cultivated in the world. A new milling system,
      which removes successive layers of the grain has been developed, the preparation
      being called a classified flour. We have detected aminopeptidase activity in the
      flour obtained from the near surface zone. Barley was the Weeah species
      cultivated in Australia. Our aim in this paper is to describe the complete
      purification of aminopeptidase from barley classified flour. Aminopeptidase
      activity was determined using L-leucine-p-nitroanilide in 10 mM sodium phosphate
      buffer, pH 7.0. Aminopeptidase was extracted in 20 mM sodium acetate buffer, pH
      5.5. Fractions (HP-1 and HP-2) were obtained upon chromatography using an HI
      propyl hydrophobic interaction column in 20 mM acetate buffer, pH 5.5, with a
      linear gradient of ammonium sulfate from 15 to 0% saturation after the ammonium
      sulfate fractionation (from 40 to 60% saturation) of the extract. The final
      purified preparation A-1-I-G was obtained from HP-1 by gel filtration,
      hydroxylapatite chromatography, diethylaminomethyl-ion exchange chromatography,
      and re-chromatography on a Sephacryl S-100HR gel column. It was pure as assessed
      by native and sodium dodecylsulfate-polyacrylamide gel electrophoreses. The
      specific activity of A-1-I-G was 64.8 fold that of the crude extract. A K(m)
      value of 0.138 mM when using L-leucine-p-nitroanilide was calculated. A-1-I-G is
      active over a wide pH range and has a strong affinity for its substrate. The
      classification process is effective as a step of enzyme purification. Also, the
      results with metal ions suggest that the enzyme is a metalloenzyme. It was
      concluded that complete purification of an aminopeptidase from barley was
      achieved.

PMID- 9147138
TI  - Antiandrogenic effect of RU-486 in the mouse kidney.
AB  - RU-486 (mifepristone) is a synthetic steroid with potent antiprogesterone and
      antiglucocorticoid activity, that is currently used as a contraceptive agent. In
      the present work we have evaluated the antiandrogenic effect of this compound on
      mouse kidney, a very well known extragenital model of androgen action by studying
      the effect of RU-486 on renal parameters that depend on androgens, such as renal
      ornithine decarboxylase (ODC) activity and kidney hypertrophy, as well as the
      inhibitory action of mifepristone on the induction of renal ODC and kidney
      hypertrophy elicited by testosterone treatment in female mice and in castrated
      male. The results showed that: (1) 48 hr after treatment of male mice with of RU
      486 (50 mg/kg, four injections) renal ODC activity decreased from 3.381 +/- 490
      nmol CO2/h.g to 605 +/- 163 (SD, n = 5); (2) in female mice or orchidectomized
      male mice, RU-486 also inhibited the renal ODC induction elicited by exogenous
      administration of testosterone propionate (TP), the magnitude of the inhibition
      was dependent on the doses of TP and RU-486 used. While RU-486 at a dose of 25
      mg/kg inhibited more than 80% ODC induction produced by treatment with 5 mg/kg
      TP, the same dose did not significantly affect ODC when the dose of TP was
      increased up to 100 mg/kg. Higher concentration of RU-486 (200 mg/kg) clearly
      inhibited the increase in ODC produced by treatment with TP 100 mg/kg; (3) RU-486
      was more effective in blocking the anabolic effects produced by stanozolol, a
      steroidal anabolizing agent, than those produced by testosterone; and (4) RU-486
      was less effective than the nonsteroidal antiandrogen flutamide in inhibiting
      renal ODC activity in male mice. Our results clearly indicate that RU-486
      possesses moderate antiandrogenic activity in mouse kidney. The possibility that
      RU-486 may have similar effects in man should be considered when using this drug.

PMID- 9147139
TI  - A comparative electrophoretic analysis of mammalian hair and avian feather
      proteins.
AB  - An improved one-dimensional sodium dodecyl sulphate separation has allowed a
      detailed electrophoretic comparison of the proteins that constitute hairs and
      feathers isolated from various representative samples of mammalian, both
      placental and marsupial and avian species. The proteins from various species were
      S-carboxymethylated using labelled (14C)-iodoacetic acid and detected both by
      Coomassie stain and fluorography. Proteins from mammalian species were compared
      with respect to their molecular masses and relative cysteine content using laser
      densitometry of both Coomassie stained gels and fluorographs of 14C labelled
      gels. These results may be quite useful forensically as an adjunct to fibre
      analysis.

PMID- 9147140
TI  - Retinyl ester storage is altered in liver stellate cells and in HL60 cells
      transfected with cellular retinol-binding protein type I.
AB  - It is suggested that cellular retinol-binding proteins are important for
      intracellular metabolism of retinol. Retinol bound to cellular retinol-binding
      proteins may be esterified with long chain fatty acids by the enzyme lecithin:
      retinol acyltransferase or may be oxidized to retinoic acid metabolites used in
      the mechanism of action of vitamin A. The aim of this present report was to
      determine whether altered levels of cellular retinol-binding protein type I
      influenced retinol storage and activation. Two different cell types have been
      examined after transfection with vectors producing sense or antisense mRNA for
      cellular retinol-binding protein type I. When HL60 cells were transfected with
      the expression vector for sense cellular retinol-binding protein type I high
      amounts of cellular retinol-binding protein type I mRNA and protein were
      produced. We observed that HL60 cells esterified less retinol than control cells
      without cellular retinol-binding protein type I. Cellular retinol-binding protein
      type I had, however, no effects on the proliferation or differentiation of HL60
      cells by retinoids. Liver stellate cells transfected with the vector for sense
      cellular retinol-binding protein type I esterified more retinol than cells
      transfected with the expression vector for antisense cellular retinol-binding
      protein type I, while retinol esterification in control cells was intermediate.
      In conclusion, our data show that cellular retinol-binding protein type I
      influences retinol esterification both in liver stellate cells and in HL60 cells.

PMID- 9147141
TI  - Can mild hyperthermia improve tumour oxygenation?
AB  - The oxygenation status of C3H mammary carcinomas, grown in the feet of CDF1 mice,
      was measured with an Eppendorf oxygen electrode. Tumours were locally heated in a
      water bath at temperatures of 38.5-41.5 degrees C for 1 h. Measurements made
      during heating showed temperature-dependent increases in tumour oxygenation.
      However, measurements performed after heating showed a rapid return to normal
      oxygenation status. Mild hyperthermia thus improves tumour oxygenation and this
      can explain the radiosensitization seen with low heat treatments, but only when
      the heat and radiation are administered concurrently, which is typically not the
      way that are given clinically.

PMID- 9147142
TI  - Intraspinal temperatures during regional deep hyperthermia induced by
      electromagnetic radiation in the Macaca mulatta.
AB  - A capacitive ring system operating at 27 MHz was tested for temperature
      distribution in the abdominal cavity of the living Rhesus monkey. Catheters were
      introduced through the abdomen and their location checked after the experiment.
      During two of these experiments a catheter was also introduced into the
      intraspinal canal. Temperature distribution was rather homogeneous within the
      abdominal cavity. Core temperature remained 3-5 degrees C below intra-abdominal
      temperatures. The intraspinal temperature increase was of the same magnitude
      compared with intra-abdominal temperature increase. Similar findings in other
      species have been reported by others. It is concluded that during non-invasive
      induction of regional hyperthermia by electromagnetic radiation, where a high
      level of energy is directed close to the spine, the intraspinal temperatures may
      be increased as high as the temperatures within the surrounding tissues. The
      central nervous system may be relatively sensitive to hyperthermia and
      hyperthermia may sensitize the spinal cord to radiation. Therefore, when
      hyperthermia is targeted at areas near the spine, either alone or in combination
      with radiotherapy applied to the tolerance limit of the spinal cord, these
      findings will have to be taken into consideration.

PMID- 9147144
TI  - Quality assurance for radiofrequency regional hyperthermia.
AB  - Today most treatments with regional hyperthermia are applied using radiofrequency
      systems with 'focus' steering by amplitude and phase control. This paper deals
      with quality assurance procedures developed to ensure controlled and safe
      treatments in such systems. Our results show how the deviations between requested
      and observed phase and amplitude vary with frequency, and how these deviations
      depend on both the geometry of the object (phantom) inside the system and the
      power level applied. The results also indicate that the investigated systems'
      internal quality assurance procedures were inadequate and that additional
      procedures should be applied. Since the system parameters depend on patient and
      treatment specific conditions it is concluded that there is a need for QA
      measurements before or during treatment. This paper deals specifically with the
      commercial BSD-2000 system from BSD Medical Corp. in Salt Lake City, Utah, as
      installed in Bergen, but the procedure outlined can be applied to other phase and
      amplitude-controlled RF-RHT systems with only minimal adjustments.

PMID- 9147143
TI  - Constitutive synthesis of heat shock protein (72 kD) in human peripheral blood
      mononuclear cells: implications for use as a clinical test of recent thermal
      stress.
AB  - There is no clinical laboratory marker to enhance the diagnosis of recent thermal
      stress in humans. The 72 kD heat shock protein, HSP 72, which is rapidly
      synthesized after heat stress could be useful in the diagnosis of illnesses
      associated with heat stress. In humans HSP, 72 is rapidly synthesized after
      thermal stress; however, conflicting data suggest it may also undergo low level
      constitutive synthesis. If HSP 72 is constitutively synthesized, a semi
      quantitative test will be necessary to detect recent heat stress; if not, a
      qualitative test would be sufficient, peripheral blood mononuclear cells were
      chosen for this investigation because they can be isolated from a small sample
      (clinically acceptable) of blood. Following heat stress Western analysis and
      autoradiography of one- and two-dimensional electrophoresis samples demonstrated
      low levels of HSP 72 in unstressed cells. HSP 72 increased with heat stress, and
      remained elevated for up to 48 h. HSP 72 mRNA was detectable in small amounts in
      nonheat stressed cells. Heat stress increased HSP 72 mRNA 1 and 2 h after stress
      and remained elevated for 6 h. HSP 72 persists long enough to be potentially
      useful as a diagnostic probe of recent heat injury; however, a semi-quantitative
      assay will be necessary.

PMID- 9147145
TI  - The effect of catheters and coatings on the performance of palladium-nickel
      thermoseeds: evaluation and design of implantation techniques.
AB  - In the development of materials for self-regulating thermoseeds much effort is
      put in improvement of the self-regulating temperature control mechanism of the
      seeds. The catheters and coatings which are needed to implant the seeds or to
      guarantee biocompatibility, generally impair the optimized performance of the
      ferromagnetic seeds. The influence of various coatings on the performance of PdNi
      seeds has been investigated by means of one-dimensional modelling and
      calorimetric experiments. Implantation using thin walled catheters is acceptable
      provided that the catheters are filled with water to assure good thermal
      coupling. Air layers inside catheters should be avoided as they reduce the sharp
      gradient of the heat production at the Curie temperature significantly. An
      alternative for the application of catheters is to insert the seeds into metallic
      needles. The effect of shielding by the metal needle can be minimized by driving
      the seed into its saturated state using a high magnetic field strength. The
      thermal interaction between the seed and surrounding tissue can also be enhanced
      by placing PdNi, e.g. tubular, on the outside of the catheter or brachytherapy
      needle. An additional advantage of this new design is an increase in the heat
      production and the quality of temperature control due to an increase in the
      amount of PdNi. For permanent implantation seeds can be coated with an inert
      metal, ceramics or plastic. The performance of the seeds is not affected by any
      of the coatings if certain conditions are met. For plastic coatings the thickness
      of the coating has to be very thin, preferably < or = 20 microns, to avoid
      thermal isolation.

PMID- 9147146
TI  - Hyperthermic modulation of resistance to cis-diamminedichloroplatinum (II) in
      human larynx carcinoma cells.
AB  - The aim of the present study was to examine the effect of hyperthermia on
      cisplatin resistance in two sublines of human larynx carcinoma HEp2 cells.
      Hyperthermia was tumouricidal for both parental and cisplatin resistant cells,
      but cisplatin resistant cells were more sensitive to the heat at 43 and 44
      degrees C. In combined cisplatin-hyperthermia treatment, heat chemosensitization
      was observed for parental, as well as for cisplatin resistant cells. At 42
      degrees C, and at 43 degrees C, the thermal enhancement ratio (TER) for cisplatin
      toxicity was higher in resistant than in parental cells. The heating at 42
      degrees C decreased the resistance factors in CA3 and CK2 cells from 2.2 and 3.5
      to 1.8 and 2.2 respectively. At 43 degrees C, the resistance factors were
      decreased to 1.7 for CA3 cells and 2.0 for CK2 cells. The heating at 43 degrees C
      increased intracellular platinum accumulation in all cell lines examined. This
      effect was more pronounced in resistant, than in parental cells, causing complete
      reversal of the reduced platinum accumulation found at 37 degrees C in resistant
      cells. In conclusion, the resistance to cisplatin was partially reversed by
      hyperthermia in CA3 and CK2 cells. Increased drug accumulation was one of the
      mechanisms involved in hyperthermic potentiation of cisplatin toxicity and
      partial reversal of cisplatin resistance in human larynx carcinoma HEp2 cells.

PMID- 9147147
TI  - Liver hyperthermia and oxidative stress: role of iron and aldehyde production.
AB  - Hyperthermia has been used to treat cancer in the liver. However, significant
      hepatotoxicity occurs at a therapeutic temperature of 42-43 degrees C. We have
      proposed that heat toxicity is the result of oxidative stress from superoxide
      generation with resultant lipid peroxidation. Further, iron release from liver
      iron stores (ferritin) appears to play a central role in hyperthermic toxicity.
      In this study, rat livers were perfused in situ at 37 or 42.5 degrees C with and
      without deferoxamine for 1 h with an asanguinous perfusate. Oxidative stress was
      assessed by the efflux of glutathione (GSH) into the perfusage. Prior studies by
      Skibba et al. (1989a, 1991) showed that perfusage equivalents of GSH were
      primarily present as oxidized glutathione (GSSG). Lipid peroxidation was assessed
      by the measurement of aldehydes appearing in the perfusate and formation of
      hydrocarbon gases (ethane and pentane) in the perfusion chamber head space. Liver
      injury was assessed by the leakage of cytosolic enzymes, AST and LDH, into the
      perfusate. Livers perfused at 42.5 degrees C showed significant rises (p < 0.05)
      in AST and LDH after 60 min of perfusion but perfusion at 42.5 degrees C with
      deferoxamine added, was not significantly different from perfusion at 37 degrees
      C. Perfusion at 42.5 degrees C caused an increase in GSH into the perfusate at a
      level significantly (p < 0.05) greater than at 37 degrees C. GSH levels in the
      liver after 60 min of perfusion decreased from 4.82 +/- 0.76 microM/gm at 37
      degrees C to 1.48 +/- 0.54 microM/gm at 42.5 degrees C (p < 0.05) but only fell
      to 3.42 +/- 1.23 microM/gm at 42.5 degrees C with deferoxamine added. Efflux of
      iron into the perfusate increase significantly with time and temperature. Low
      molecular weight chelated iron within the liver after perfusion increased from
      5.88 +/- 1.46 nM/gm at 37 degrees C to 25.8 nM/gm at 42.5 degrees C (p < 0.05).
      Perfusate total aldehyde levels increased from 0.085 +/- 0.056 to 0.32 +/- 0.09
      microM/ml after 60 min at 37 degrees C and 0.87 +/- 0.45 to 2.01 +/- 0.90
      microM/ml at 42.5 degrees C (n = 8). There was a significant decrease in total
      aldehyde levels at 42.5 degrees C with the addition of deferoxamine to the
      perfusate, 0.36 +/- 0.14 to 0.86 +/- 0.27 microM/ml, when compared to 42.5
      degrees C levels (p < 0.05). Levels of ethane and pentane in the perfusion
      chamber head space showed no significant changes with time or temperature of
      perfusion. The data suggest that lipid peroxidation may play a causal role in
      hyperthermia induced liver toxicity and that iron plays a major role in this
      injury. Failure of hydrocarbon analysis to support this conclusion appears
      related to the use of membrane oxygenators.

PMID- 9147148
TI  - Correlation between cell killing effect and cell membrane potential after heat
      treatment: analysis using fluorescent dye and flow cytometry.
AB  - Exposure of mammalian cells to a temperature between 42 and 44 degrees C produces
      multiple effects on cellular metabolism. However, none of these effects have been
      demonstrated to be casually related to cell death. The plasma membrane has also
      been suggested to be one of the targets for hyperthermia. Hyperthermia influences
      the membrane fluidity and membrane fluidity affects both passive diffusion and
      active transport process. Here, we examined the effect of hyperthermia on the
      transmembrane potential V-79 cells using a lopophilic probe and flow cytometry.
      The underlying principle on which this method is based is that a freely
      diffusible cation distributes itself across the membrane according with the
      transmembrane potential and with the concentration gradient. By these methods, we
      tried to find the relation between the change of surviving fraction and membrane
      potential. We revealed that the membrane potential becomes to be depolarized by
      heat treatment between 41 and 44 degrees C immediately after heat treatment. In
      the relationship between the change in membrane potential and cell surviving
      fraction, the difference between 43 and 44 degrees C was not statistically
      significant but between 42 and 43 degrees C was statistically significant. These
      results imply that the cell membrane (potassium ion channel) is one of the
      targets of heat treatment and that duration of depolarized condition leads to
      cell death.

PMID- 9147149
TI  - Bioluminescence imaging of metabolites in a human tumour xenograft after
      treatment with hyperthermia and/or the radiosensitizer pimonidazole.
AB  - The levels and distribution of ATP, glucose and lactate in human tumour
      xenografts following either single or combined treatment with hyperthermia (43
      degrees C for 30 min) and/or pimonidazole (1 mg/g b.w) were determined by
      bioluminescence and compared with the mean 'global' levels obtained from the same
      tumours using conventional biochemical analysis. In general, the levels of ATP,
      glucose and lactate measured with both methods were in good agreement although
      the latter was consistently lower after bioluminescence determination. Compared
      with controls, neither the levels of ATP nor glucose were greatly affected in
      this tumour following treatment with the various modalities, whereas those of
      lactate were considerably increased as determined by both methods. The spatial
      distribution of ATP and glucose from controls and treated tumours was largely
      confined to the periphery and generally remained unchanged irrespective of
      treatment without any apparent alterations in the shape of the distribution
      curve. However, the increased lactate levels tended to accumulate towards the
      central region of the tumour after hyperthermia and/or sensitizer, showing an
      almost Gaussian-like distribution compared with controls. These results are in
      agreement with previous studies of global tumour metabolism showing an enhanced
      glycolytic activity with increased lactate levels after single or combined
      modality treatment.

PMID- 9147150
TI  - Effect of lactic acid in tumours on antitumour activity of hyperthermia.

PMID- 9147151
TI  - Intracorporeal whole body hyperthermia: toxicity assessment.

PMID- 9147152
TI  - Clinical management of syncope and seizures in GUM clinics.

PMID- 9147153
TI  - Update on contraception.

PMID- 9147154
TI  - Syphilis in injecting drug users: clues for high-risk sexual behaviour in female
      IDUs.
AB  - The objective was to measure the gender-specific differences for syphilis and for
      the sexual transmission of human immunodeficiency virus (HIV) in a cross
      sectional analysis of injecting drug users (IDUs) admitted to detoxification
      between February 1987 and January 1990. HIV was determined by enzyme-linked
      immunosorbent assay (ELISA) and confirmed with Western blot. For syphilis
      reactive samples to a rapid plasma reagent (RPR) were confirmed with treponemal
      tests (FTA-ABS or MHA-TP). Of the 386 heterosexual IDUs, 68% were HIV-positive
      and 4.7% had serologic syphilis (RPR and FTA-ABS or MHA-TP positive). Syphilis
      was higher in women (12%) than in men (3%), and women reported a significantly (P
      < 0.001) higher number of sex partners. Men had an IDU as a sex partner more
      often than women did (P = 0.001). Serologic syphilis in women was associated with
      having had more than one sexual partner in the previous year (P = 0.028) but this
      association was not present in men. HIV infection was not associated with
      syphilis in male IDUs. However, HIV was present in all women with syphilis that
      reported more than one partner.

PMID- 9147155
TI  - Determination of factors associated with condom use among women infected with
      human immunodeficiency virus.
AB  - To better understand potential barriers to condom use and the sexual behaviour of
      women infected with human immunodeficiency virus (HIV), an anonymous self
      administered survey was performed on a convenience sample of 83 predominantly
      single HIV+ women. Most women had only one sexual partner who usually knew of the
      subject's serostatus. Only a minority of partners (26%) were known to also be HIV
      infected. Subjects were surprisingly more likely to use condoms with their main
      partner as opposed to other partners. Factors found to be associated with condom
      non-use included younger age, low education level, partner HIV+, history of a
      sexually transmitted disease (STD), and use of drugs or alcohol during sex.
      Although most subjects indicated the decision was mutual when deciding not to use
      a condom, 20% stated it a was a partner decision. Future intervention efforts
      should target these identified high-risk individuals and optimally involve the
      partners of HIV-infected women.

PMID- 9147156
TI  - Hospital and hospice resource use of HIV-positive patients in Edinburgh.
AB  - A prospective study of health service and hospice resource utilization (average
      length of stay or ALOS, discharge rate, bed day use, outpatient consultation)
      analysed with reference to gender, risk activity, immunological and clinical
      staging (1987 definition of AIDS) for the financial year 1992-93 was undertaken
      at the Regional Infectious Disease Unit (RIDU), City Hospital, Edinburgh,
      Scotland where 72% of 513 patients were infected via injection drug use. Not
      surprising therefore overall, drug users were the heaviest users of the inpatient
      facilities (74% of the discharges and 65% of the bed days) although homosexuals
      had the highest discharge rate (114 per 100 person years) and rate of bed day use
      (1654 days per 100 person years). Immunodeficiency (CD4 count < 200 cells/ul) and
      a clinical diagnosis of AIDS were both associated with greater inpatient and
      outpatient resource use compared to those without immunodeficiency (CD4 count >
      or = 200 CD4 cells/ul) or AIDS. Gender effects were complex; the ALOS for women
      was increased for all risk groups whatever the CD4 count whilst there was no
      consistent trend of more resource use for women by risk group. Drug users were
      the heaviest overall users of the local hospice (84% of all admissions, 83% of
      the bed days and a discharge rate of 76.4 per 100 person years), more than double
      the rates experienced by the other risk groups. Thus both clinical and
      immunological staging (AIDS or a CD4 count < 200 cells/ul) were associated with
      increased resource use in HIV infection and estimates of resource use for AIDS
      need to be increased by around one-third to take into account hospice use.
      Despite the preponderance of drug users in Edinburgh, comparisons with other
      centres did not reveal increased resource use.

PMID- 9147157
TI  - Condom and nonoxynol-9 use and the incidence of HIV infection in serodiscordant
      couples in Zambia.
AB  - We aimed to measure the effectiveness of latex condoms and of nonoxynol-9 [N-9]
      spermicides, in preventing HIV transmission in heterosexual serodiscordant
      couples in Lusaka. Each couple was examined at clinic visits scheduled at 3-month
      intervals for one year or more per couple, or until seroconversion or
      discontinuation. Couples were given condoms and their choice of 3 N-9 products
      and advised to use both at every intercourse. Sexual exposure was ascertained
      from coital logs that recorded coitus and barrier method use. HIV serological
      testing was done at each clinic visit (ELISA and Western blot if positive). One
      hundred and ten discordant couples were followed for a mean of 17.6 months.
      Seventy-eight per cent of coital episodes were protected by condoms, 85% by
      spermicides and 6.4% were unprotected. Fourteen seroconversions occurred (8.7
      infections per 100 couple-years [c-y]). The rate was higher among seronegative
      men than seronegative women. Among couples who reported using condoms at every
      intercourse the infection rate was 2.3/100 c-y, compared with 10.7/100 c-y among
      couples using condoms less consistently (rate ratio [RR] 0.2; 95% confidence
      interval [CI] 0-1.6). Among couples who reported using N-9 at every intercourse,
      the seroconversion rate was 6.9/100 c-y; among couples who reported less than
      full-time N-9 use, the rate was 8.9/100 c-y (RR 0.8; 95% CI 0.2-2.8). Among the
      subset of female seronegatives, the N-9 RR was 0.5 (95% CI 0.1-3.8). But when we
      calculated HIV rates according to N-9 consistency in coital acts when condoms
      were not used, there was no evidence of protection with higher N-9 use.
      Consistent use of latex condoms reduces the incidence of HIV infection, but the
      association between N-9 spermicides and HIV is less clear. The current study
      could not provide compelling data on the impact of N-9 spermicide use on risk of
      HIV infection. The study's small size, as well as the consistency of concurrent
      condom use, limited our inferences. Available spermicide products must be studied
      further.

PMID- 9147158
TI  - Psychological stress and depression in older patients with intravenous drug use
      and human immunodeficiency virus infection: implications for intervention.
AB  - We aim to assess the age-related differences in psychological stress and
      depression in patients with human immunodeficiency virus (HIV) infection.
      Prospective, longitudinal, observational study of patients with HIV followed at a
      university affiliated VA Medical Center. Fifty-six consecutive patients with HIV
      infection aged 19-68 were studied. Data on demographics, living arrangements,
      education, employment, income, social, religious, and community support, medical
      status, psychological stress, depression, and coping was assessed at baseline and
      every 6 months. Instruments for psychological testing included Beck Depression
      Inventory, Profile Mood Status (POMS) scale and ways of coping scale (inventory
      of coping with illness scale). Sixty-nine per cent (38/56) of the patients were
      older than 35 years of age. Older patients exhibited significantly greater
      emotional and psychological stress; the mean POMS score for older patients was
      56.8 as compared to 21.5 for younger patients (P = 0.004). Older patients had
      significantly greater depression (P = 0.001), higher tension and anxiety (P =
      0.005), greater anger and hostility (P = 0.03), greater confusion and
      bewilderment (P = 0.01), and more fatigue (P = 0.003) as compared with younger
      patients. Older patients were significantly more likely to have intravenous drug
      use as an HIV risk factor (P = 0.02), less likely to be employed (P = 0.005), and
      more likely to use non-traditional therapies (P = 0). Intravenous drug use was an
      independent predictor of psychological stress in older patients. Patients with
      HIV, older than 35 years of age, are significantly more likely to suffer from
      depression and psychological stress; intravenous drug use was an independent
      predictor of stress. Interventions for the treatment of depression should be
      especially sought in this subgroup of patients with HIV.

PMID- 9147159
TI  - Application of 'Clearview Chlamydia' for the rapid detection of cervical
      chlamydial antigen.
AB  - In a study to evaluate the Clearview chlamydia test in a genitourinary medicine
      clinic, the sensitivity and specificity were 76.4% and 99.4% respectively when
      compared with the DAKO IDEIA chlamydia test processed in a department of medical
      microbiology. The time taken to perform and read the Clearview chlamydia test 'on
      site' did not interfere with the normal routine functioning of the clinic and the
      nurses who performed it as part of their routine duties found it simple and easy
      to use.

PMID- 9147160
TI  - Prevalence of Mycoplasma genitalium in asymptomatic men in Japan.
AB  - We aim to clarify the prevalence of Mycoplasma genitalium in asymptomatic men in
      Japan. First-catch urine specimens were obtained from 187 asymptomatic Japanese
      men and examined for the presence of M. genitalium using a polymerase chain
      reaction (PCR)-based assay. Two (1.1%) of 187 first-catch urine specimens were
      positive for M. genitalium. The prevalence of M. genitalium in urine specimens of
      asymptomatic men in Japan is lower than that in asymptomatic men in the UK (6%)
      and Denmark (9%).

PMID- 9147162
TI  - The judicial response to HIV/AIDS.

PMID- 9147161
TI  - Infection with HIV, syphilis and hepatitis B in Ethiopia: a survey in blood
      donors.
AB  - Sera of all male donors appearing at the blood bank of a regional hospital in
      Northwest Ethiopia in 1994 (n = 1022) and 1995 (n = 1164), were screened for the
      presence of human immunodeficiency virus (HIV-1) and treponemal antibodies.
      Additionally, screening for hepatitis B surface antigen (HBsAg) was carried out
      on 549 consecutive sera. In 1995, the crude seroprevalence of HIV-1 infection and
      syphilis was 16.7% and 12.8%. Seroprevalence of HBsAg was 14.4%. HIV and syphilis
      seroprevalence was highest in soldiers (30.6% and 20.9%) and daily workers (18.8%
      and 13.5%), and lowest in farmers (8% and 6.7%). However, farmers had the highest
      rate of HBsAg (18.8%). HIV-positive donors had an increased risk for being
      positive for syphilis antibodies (OR = 3.69, 95% CI = 2.69-4.96), but not for
      HBsAg (OR = 0.79, 95% CI = 0.36-1.67). The data indicate that (i) the HIV
      epidemic has not yet reached a plateau phase in Ethiopia, and (ii) the
      transmission and epidemiology of HBsAg in Ethiopia is different from that of HIV
      and syphilis.

PMID- 9147163
TI  - The management of acute myeloid leukaemia (AML) in human immunodeficiency virus
      (HIV) infection: a case report and review.

PMID- 9147165
TI  - Inoculation of culture plates: straightforward or is it?
AB  - In view of the recent vogue in some genitourinary medicine (GUM) units towards
      selective microscopy we aimed to assess the adequacy of culture plate inoculation
      in our own GUM clinic by the visual examination of 350 consecutively inoculated
      plates. Seventy-five (21%) plates were inoculated so lightly that no indentation
      in the agar could be seen whilst in 20 (60%) the agar was shredded. Eighty-five
      per cent of inadequately plated samples were inoculated by the same staff members
      who were either relatively inexperienced, or well-distanced from their last in
      service training. This has many important implications not only in the
      identification and control of infection but also with respect to staff training.
      We have now introduced practical plating instruction for all new members of
      clinical staff and additional in-service training. We plan to repeat the audit in
      6 months' time to assess the effect of these changes.

PMID- 9147164
TI  - Rapidly progressive syphilis in early HIV infection.

PMID- 9147166
TI  - Rapid rise in HIV prevalence among women attending government STD clinic in
      Mumbai (Bombay), India.

PMID- 9147167
TI  - Cognitive test performance in a community-based nondemented elderly sample in
      rural India: the Indo-U.S. Cross-National Dementia Epidemiology Study.
AB  - Interpretation of cognitive test performance among individuals from a given
      population requires an understanding of cognitive norms in that population.
      Little is known about normative test performance among elderly illiterate non
      English-speaking individuals. An age-stratified random sample of men and women,
      aged 55 years and older, was drawn from a community-based population in the rural
      area of Ballabgarh in northern India. These Hindi-speaking individuals had little
      or no education and were largely illiterate. A battery of neuropsychological
      tests, specially adapted from the CERAD neuropsychological battery, which was
      administered to this sample, is described. Subjects also underwent a protocol
      diagnostic examination for dementia. Norms for test performance of 374
      nondemented subjects on these tests are reported across the sample and also by
      age, gender, and literacy.

PMID- 9147168
TI  - Validation of the NOSGER (Nurses' Observation Scale for Geriatric Patients):
      reliability and validity of a caregiver rating instrument.
AB  - The Nurses' Observation Scale for Geriatric Patients (NOSGER) is a rating scale
      for use in geriatric patients that can be applied by nurses or other caregivers.
      It deals with the daily behavior of elderly patients and measures impairment in
      six areas (dimensions): memory; instrumental activities of daily living (IADL);
      (basic) activities of daily living (ADL); mood; social behavior; and disturbing
      behavior. Objectivity, stability, construct validity, and acceptance of the scale
      have been established in previous studies using an earlier version of the NOSGER.
      The present validation study considered 50 healthy old subjects, 25 patients with
      mild dementia, 25 patients with advanced (mostly moderate according to DSM-III-R
      criteria) dementia, and 25 elderly patients with depression. The NOSGER was
      completed by relatives in the case of subjects living in their own homes and by
      nurses or other caregivers for institutionalized subjects. In addition to the
      NOSGER, selected tests of concentration, memory, and performance were applied as
      outside criteria. Interrater reliability (objectivity) was estimated by variance
      component analysis. Values between rtt = .68 and rtt = .89 (all p < .001) were
      found for the six NOSGER dimensions, the values being higher for the cognitive
      dimensions (memory, IADL, ADL) than for the noncognitive ones (mood, social
      behavior, disturbing behavior). Retest reliability (stability), which was
      calculated via rank order correlations, was somewhat higher for the cognitive
      NOSGER dimensions (memory rs = .91, IADL rs = .92, ADL rs = .88; p < .001) than
      for the noncognitive ones (mood rs = .85, social behavior rs = .87, disturbing
      behavior rs = .84; p < .001). All these values satisfy the level of rtt > or =
      .80 required in accordance with psychometric standards. The concurrent validity
      of the NOSGER dimensions was assessed using correlations with external criteria
      with which similarity of content was expected. The NOSGER dimensions memory,
      IADL, ADL, and social behavior were found to correlate closely with external
      criteria of similar content, whereas no satisfactory concurrent validities were
      found for the dimensions mood or disturbing behavior. The NOSGER dimensions were
      also correlated with a number of unrelated external criteria so as to reveal any
      discordances. For the dimensions memory, IADL, ADL, and social behavior, no clear
      cut discriminant validities were found. This suggests that these four dimensions
      may function as parameters not just of different areas of behavior, but also of a
      general factor that might be described as "cognitive intactness." As a further
      aspect of construct validity, significant differences (all p < .001) between the
      four groups of subjects were found in five of the six NOSGER dimensions (memory,
      IADL, ADL, mood, social behavior): The healthy subjects differed significantly
      from all three patient groups in five of the six dimensions; the moderately
      demented group differed from the depressed group in four of the six dimensions
      and from the mildly demented group in two of the six dimensions; and the mildly
      demented group differed significantly from the depressed group in terms of mood
      (significance levels are after application of the Bonferroni correction).
      Significant group differences (p generally < .001) were also found for most of
      the objective performance tests used (data not presented).

PMID- 9147169
TI  - P2 flash visual evoked response delay may be a marker of cognitive dysfunction in
      healthy elderly volunteers.
AB  - In an earlier study, 31 healthy elderly volunteers had normal cognitive function
      as measured by the Mini-Mental State Examination. Twenty-seven returned for
      further memory testing using the Wechsler Memory Scale-Revised (WMS-R). The P2
      latency of the flash visual evoked response was positively correlated with age (p
      = .0008), but was not significantly related to gender. Nine of these 27
      putatively healthy subjects had a delayed P2, suggestive of dementia. Although
      unaware of any memory deficits, 5 of the 27 had WMS-R Visual Memory Span
      percentile scores 1 or more standard deviations less than age-matched controls.
      Four of the five also had a significantly delayed P2 component. This positive
      correlation, adjusted for age, between poor Visual Memory Span performance and a
      delayed P2 was statistically significant (p < .025). These findings suggest that
      a delayed P2 in putatively healthy subjects is indicative of a visuospatial
      deficit which might be a precursor of dementia later.

PMID- 9147170
TI  - A dynamic long-term care system for the demented elderly.
AB  - The dynamic processes and the way they interact in shaping a care system for
      demented patients are analyzed and discussed. The development of
      disability/dependency, interpreted in a simulation model based on Katz's index of
      ADL and Berger's scale "Rating the severity of senility," gave insight into the
      interplay of four care levels: psychogeriatric long-term care for patients with
      severe behavioral disturbances, nursing-home care for patients with highly
      reduced ADL capacity who are often moderately to severely demented, group-living
      care for the demented with less dominating ADL dependency, and residential care
      for the elderly frail with or without symptoms of dementia. For each facility in
      this chain of care, characteristics in patients' symptomatology and behavior
      could also be identified. Resources necessary in order to fulfill goals in caring
      differed between each facility.

PMID- 9147171
TI  - Change mechanisms of support groups for caregivers of dementia patients.
AB  - The support group is an important means of providing help to families of demented
      elderly. In the Netherlands, the support group is widely used in mental health
      care. (Quasi-)experimental studies, however, have not established its
      effectiveness. In this article, an overview of the Dutch support groups and a
      review of the literature are given. In addition, a study among 110 participants
      of support groups is presented. Quantitative analyses show that the support group
      is especially effective in caregivers who are dissatisfied about their role as
      caregiver and have no job. Support groups are also more effective when the
      elderly person is more apathetic and lives in a nursing home. Interviews with
      caregivers show that the participants experience four forms of support:
      information, advice on how to cope with the situation, and moral and emotional
      support. These ways of support provide caregivers with a better perspective on
      their situation and help them to better cope with problems and emotions.

PMID- 9147172
TI  - Family and physicians' views of surrogate decision-making: the roles and how to
      choose.
AB  - Physicians and family members were compared on the roles played in surrogate
      decision-making and their views as to how choices should be made by surrogate
      decision-makers. Thirty-six family members of patients with Alzheimer's disease,
      35 family members of patients with schizophrenia, and 34 physicians from a
      diversity of specialties were the respondents. There was general agreement that
      shared decision-making was preferred. Physicians seem to make surrogate decisions
      in accordance with contemporary views about their roles. Families believed they
      had a strong subjective appreciation of the patient's overall good. The burden of
      decision-making was greater for families, but that depended to some degree on the
      diagnosis of the patient.

PMID- 9147173
TI  - Drug treatment of schizophrenia and delusional disorder in late life.
AB  - As people live longer, an increasing proportion of patients with schizophrenia
      and delusional disorder will be elderly. Little has been published on treatment
      response, effective treatment strategies, or the use of atypical neuroleptics in
      this group. This review of the literature explores documented response rate,
      route and dose of neuroleptic, indicators of poor response, and the use of novel
      drugs. Despite great variation in the neuroleptic dose ranges employed, patients
      with late-onset disease often continue to experience psychotic symptoms.
      Compliance with treatment is the most important determinant of outcome. Atypical
      neuroleptics are specifically indicated for patients with visual hallucinations
      or extrapyramidal symptoms. Elderly psychotic patients should be treated as
      vigorously and with as wide a range of neuroleptics as their younger
      counterparts. Physicians should not restrict drug doses to modest levels in all
      cases as long as patients are monitored frequently for the emergence of side
      effects.

PMID- 9147174
TI  - Depression in persons with dementia.
AB  - The prevalence of depression in persons with dementia is controversial. Among 288
      outpatients with dementia, a prevalence of 7.4% was found according to the
      Hamilton Rating Scale for Depression (HRSD), 8.0% using the Geriatric Depression
      Scale (GDS), and 6.3% according to DSM-IV criteria. Rates and levels of
      depression tended to be higher in vascular than in Alzheimer's dementia according
      to the rating scales, but not according to the DSM-IV criteria. Greater cognitive
      impairment was associated with higher HRSD (but not GDS) scores. Cases of
      clinical depression did not persist over 12 months' follow-up. These results
      suggest that clinically significant depression in dementia is less common than
      previously reported and tends to remit.

PMID- 9147175
TI  - Suicidal plans in patients with stroke: comparison between acute-onset and
      delayed-onset suicidal plans.
AB  - Three hundred one patients were examined for suicidal plans during the acute
      hospital period following stroke and at 3, 6, 12, and 24 months' follow-up. It
      was found that 6.6% of patients developed suicidal plans during the initial in
      hospital evaluation (acute-onset suicidal plans) and 11.3% of patients developed
      suicidal plans at 3, 6, 12, or 24 months' follow-up (delayed-onset suicidal
      plans). The development of both acute and delayed-onset suicidal plans was
      strongly related to the existence of depressive disorders, especially major
      depression, and to a prior history of stroke. Acute-onset suicidal plans were
      also related to premorbid alcohol abuse. Acute-onset suicidal patients had more
      anterior lesion location and delayed-onset suicidal patients had more posterior
      stroke lesions. Delayed-onset suicidal plans were not related to alcohol abuse
      but tended to be associated with greater physical impairment and poorer social
      support during the acute poststroke period. These data suggest that the etiology
      of these two types of suicidal plans may be different with acute onset related to
      biological mechanisms and delayed onset related to psychological mechanisms.

PMID- 9147176
TI  - Social and psychosocial factors predicting depression in old age: a longitudinal
      study.
AB  - The predictive value of social and psychosocial factors for the occurrence of
      depression in elderly Finns is described using a longitudinal design. A
      population determined as not being depressed in an epidemiological study in 1984
      1985 was clinically interviewed and examined in a follow-up study in 1989-1990 (N
      = 679). The potential predictive factors for depression were analyzed by
      contrasting the persons depressed in 1989-1990 with the ones not depressed. In
      men, depression was predicted by a poor relationship with one's wife and feelings
      about low appreciation of old persons or of the participant himself during the
      initial study and the loss of a mother while under 20 years of age. Certain
      changes and life events during the follow-up were related to the occurrence of
      depression in men, such as a change in the relationship with one's wife into a
      poorer direction, a decrease in the amount of hobbies, getting married, a
      grandchild's divorce, separation from someone important, moving into long-term
      institutional care, giving up hobbies or a position in a voluntary organization,
      and alcohol problems of a close person. In women, depression was predicted by
      living together with one's husband, living with other people, and a low activity
      in participating in religious events during the initial study and a loss of
      father while under 20 years of age. The risk of women living alone was lower
      compared to women not living alone. Also, certain changes and life events during
      the follow-up were associated with a high risk of depression in women, including
      a change in the relationship with one's neighbors into a poorer direction, an
      increase in the amount of time spent alone, a decline of the social activity
      level, getting married, occurrence of serious marital problems, separation from
      someone important, giving up hobbies or a position in a voluntary organization,
      alcohol problems of a close person, and a small number of social growth events.
      The results support the hypothesis about psychosocial factors playing a role in
      the etiology of depression in old age.

PMID- 9147177
TI  - Psychiatric symptoms in patients with dementia treated in a psychogeriatric day
      hospital.
AB  - Sixty-five consecutive patients with dementia, treated at a psychogeriatric day
      hospital, were studied regarding prevalence of psychiatric symptoms. The clinical
      diagnoses were dementia of the Alzheimer type (n = 19), vascular dementia (n =
      27), mixed Alzheimer's disease and vascular dementia (n = 13), vascular dementia
      of frontal type (n = 2), and other diseases (n = 4). Mean age at referral was
      75.6 +/- 6.6 years and the average treatment time was 21 +/- 14 months. About 90%
      of the patients showed one or several significant psychiatric symptoms during the
      course of dementia. Most common were delirious episodes, anxiety, sleep
      disturbances, and depressed mood. The relationship between clinical features and
      the type and duration of dementia was analyzed. Sleep disturbances and depressed
      mood often appeared early, whereas misidentification and delusions became more
      prevalent later in the course of dementia. The results indicate that the
      psychogeriatric day hospital may offer effective and flexible care and support to
      demented persons living at home.

PMID- 9147178
TI  - Long-term treatment of elderly individuals with emotional disturbances: an open
      study with citalopram.
AB  - In the present open study, the long-term safety, tolerability, and efficacy of
      citalopram in the treatment of elderly people with emotional disturbances were
      studied. One hundred twenty-three elderly patients with symptoms of depression
      anxiety were included. Most of the patients (76%) were demented. Fifty-two
      patients completed a 12-month treatment. Irritability, depressed mood, anxiety,
      restlessness, and fear-panic were significantly reduced. The severity of illness
      from baseline to Month 9 was rated as significantly improved. The side effects
      were infrequent and mostly mild.

PMID- 9147179
TI  - Squalor syndrome and psychogeriatric admissions.
AB  - A series of patients with the squalor syndrome who were admitted to a
      psychogeriatric ward were compared with those without the syndrome. Patients with
      squalor syndrome received a greater number of services prior to admission, were
      less likely to be on psychotropic medication prior to admission, had longer
      length of hospital admission, and were discharged to a "more dependent"
      accommodation facility. These findings, methodological difficulties, and avenues
      for future research are discussed.

PMID- 9147180
TI  - Multicenter genetic study of retinitis pigmentosa in Japan: I. Genetic
      heterogeneity in typical retinitis pigmentosa.
AB  - A nationwide, multicenter study of typical retinitis pigmentosa (RP) was carried
      out in collaboration with 18 hospitals throughout Japan to obtain current
      information for genetic counseling. We analyzed the genetic heterogeneity of RP
      based on the parental consanguinity of 434 probands registered during a 6-month
      period in 1990. A gradual decline in the frequency of consanguineous marriage was
      recognized among the normal parents of RP patients. The relative frequencies of
      inheritance patterns were estimated as: autosomal recessive, 25.2%; autosomal
      dominant, 16.9%; X-linked, 1.6%; and simplex, 56.3%. A comparison of these
      results with previous reports in Japan revealed a decline in the relative
      frequency of autosomal recessive cases and an increase in simplex cases. This
      suggests a decrease in the incidence of autosomal recessive retinitis pigmentosa
      in Japan, as well as the necessity for exhaustive investigations aimed at
      identifying inheritance patterns for RP patients seeking genetic counseling.

PMID- 9147182
TI  - Ultrasound biomicroscopic corneal thickness measurement for corneal thickness
      mapping.
AB  - Digitalized ultrasound biomicroscopic measurements of vertical cross sections
      from a 5 mm diameter area of the central cornea of normal and morbid eyes were
      used to create a computerized corneal thickness map. Mean corneal thickness in
      normal eyes was 0.503 +/- 0.027 mm; the coefficient of variation, an index of
      reproducibility, was < 10% in all eyes.

PMID- 9147183
TI  - Trochlear nerve palsy associated with superficial siderosis of the central
      nervous system.
AB  - A 56-year-old man with superficial siderosis of the central nervous system (SSCN)
      presented with complaints of trochlear palsy, visual field defects, gait ataxia,
      and hearing loss. He had no history of trauma and there were no signs of tumors
      or aneurysms. T2-weighted magnetic resonance imaging demonstrated characteristic
      hypointensity in the meninges. We believe that SSCN should be added to the
      differential diagnosis of trochlear nerve palsy.

PMID- 9147181
TI  - Multicenter genetic study of retinitis pigmentosa in Japan: II. Prevalence of
      autosomal recessive retinitis pigmentosa.
AB  - Retinitis pigmentosa (RP) is a group of genetically heterogeneous diseases with
      autosomal recessive (AR), autosomal dominant, and X-linked modes of inheritance.
      Autosomal recessive retinitis pigmentosa (ARRP) is the most common form in Japan.
      A genetic analysis was done to determine the prevalence of ARRP indirectly, to
      provide an estimation of changing trends in the overall prevalence of RP. Data on
      the frequency of consanguinity and marriage year of normal parents of 59 ARRP
      patients were obtained from a nationwide multicenter survey of typical retinitis
      pigmentosa conducted in 1990. The gene frequency of ARRP was 0.01145 (Dahlberg's
      formula). In 1990, the number of young symptomatic ARRP patients decreased, while
      the number of patients aged 40 years and older increased. The total number of
      symptomatic ARRP patients in 1990 was nearly 21% higher than in 1970. Despite a
      dramatic decline in consanguinity in recent decades in Japan, the number of ARRP
      patients has increased. This increase is attributed to greater longevity and
      overall population growth. Our results suggest that the total number of RP
      patients has not decreased, and may even have increased.

PMID- 9147184
TI  - Restrictive strabismus after retrobulbar anesthesia.
AB  - Two rare cases of strabismus resulting from contracture of the extraocular rectus
      muscles after retrobulbar anesthesia for cataract surgery are described. Clinical
      signs in both cases suggested that the development of the impaired function of
      the lateral and superior rectus muscles followed the same pattern: initial
      stimulation followed by paretic and restrictive stages. Abnormal enlargement of
      the muscles was identified by computed tomography (CT) and magnetic resonance
      imaging (MRI). The data indicate that the strabismus was the result of direct
      injection of anesthetics into the rectus muscle.

PMID- 9147185
TI  - Olfactory neuroblastoma in northern Thailand.
AB  - Two cases of olfactory neuroblastoma in women in northern Thailand are described.
      Original complaints were severe headaches and eye pain; death occurred from
      intracranial extensions 6 months and 1 year after diagnosis. Results of study
      with light microscopy, immunohistopathology, and electron microscopy are
      reviewed, and several management recommendations are discussed.

PMID- 9147186
TI  - Effects of adrenergic agents and phosphodiesterase inhibitors on outflow facility
      and cell shape of bovine trabecular meshwork.
AB  - Changes in the outflow facility of perfused calf eyes and in the shape of cells
      in cultured trabecular meshwork (TM) have been studied, following exposure to
      adrenergic agents and phosphodiesterase inhibitors (PDE). Dobutamine caused
      confluent TM cells to change their usual polygonal shape to a characteristic
      stellate shape. Salbutamol had no effect, but PDE inhibitors,
      isobutylmethylxanthine (IBMX), theophylline, and caffeine were very effective in
      producing this shape change. Epinephrine, isoproterenol, dobutamine, and
      salbutamol did not increase the outflow facility, either at 22 degrees C or 36
      degrees C, while theophylline, caffeine, and IBMX did increase it in a dose
      dependent manner. On the other hand, the high concentrations of beta-adrenergic
      agents required to produce even a small change in outflow facility and cell shape
      argue against the involvement of adrenergic-receptor mediation and may suggest
      another mechanism; on the other, the enhancement of epinephrine effects by PDE
      inhibitors and the similar effect produced by cyclic adenosine 3',5'-cyclic
      phosphate (cAMP) and purines suggest that changes in the cell shape are produced
      by beta-receptor activation. The beta-adrenergic agents were not effective in
      changing outflow facility, but the PDE inhibitors were remarkably effective both
      in changing the shape and in increasing facility.

PMID- 9147187
TI  - Nicardipine modification of endothelin-1 effects on visual evoked potential.
AB  - Endothelin-1 (ET-1), a vascular endothelium-derived peptide, regulates
      microcirculation by modulating Ca2+ ion channels. Intravitreally injected ET-1
      constricts retinal vessels and reduces blood flow in the optic nerve capillaries.
      We examined the antagonistic effect of a calcium-ion channel blocker,
      nicardipine, on ET-1 effects on visual evoked potential (VEP). ET-1 (10(-6); 10
      microL) was injected into the posterior vitreous of rabbit eyes. Intravenous
      nicardipine (20 micrograms/kg) was also given, and VEP was monitored for 2 hours
      following injection. Thirty minutes after injection, ET-1 had reduced VEP
      amplitude to 42.6% of the baseline level. The reduction effect continued for the
      remainder of the study. Nicardipine suppressed the ET-1-induced reduction of VEP
      amplitude (P < 0.05, Scheffe). The vasospasm produced by ET-1, which reduces the
      VEP amplitude, involves the CA2+ ion channel. Since nicardipine interferes with
      the activity of ET-1, we believe that Ca2+ channel blockers can be useful in the
      treatment of ischemic retinal and optic nerve disorders that are related to
      abnormal ET-1 production.

PMID- 9147188
TI  - Accommodation and pupilloconstriction areas in the cat midbrain.
AB  - The results of our previous studies suggest that the rostral superior colliculus
      (SC) is involved in the control of accommodation in the cat. The accommodation
      related area in the rostral SC projects into the pretectum and the mesencephalic
      reticular formation (MRF), indicating that these areas may also be involved in
      the control of accommodation. In this study, we tried to identify cat midbrain
      areas of accommodation and pupilloconstriction control by systematically mapping
      microstimulation responses. Three regions were found to evoke the accommodation
      response: the posterolateral pretectum, including the nucleus of the optic tract
      and the posterior pretectal nucleus; the posteromedial pretectum, including the
      nucleus of the posterior commissure (NPC) and adjacent commissural fibers; and
      the MRF area dorsolateral to the oculomotor nucleus. Pupilloconstriction was
      evoked by microstimulation of the posteromedial pretectum around the NPC and the
      anterior pretectum around the olivary pretectal nucleus.

PMID- 9147189
TI  - Real-time measurement of human optic nerve head and choroid circulation, using
      the laser speckle phenomenon.
AB  - A modification of a previously described instrument that used the laser speckle
      phenomenon for noncontact two-dimensional analysis of the fundus tissue
      circulation was devised so that tissue circulation in the optic nerve head (ONH)
      or choroid of the human eye could be measured on a real-time basis. The fundus
      was illuminated by a diode laser spot and the image speckle was recognized by an
      area sensor. A quantitative index of blood velocity, normalized blur (NB), was
      calculated by a logistic board every 0.125 seconds for 7 seconds. Using this
      modified device, the average NB of the measurement field in the temporal ONH,
      free of visible surface vessels (NBONH), and that in the posterior choroid (NBch)
      of normal human eyes were measured. The coefficients of reproducibility of 1
      minute interval measurements were 11.7% for the NBONH) and 8.7% for the NBch
      (each, an average of 5 pulses), and those of 24-hour interval measurements were
      13.0% (NBONH) and 9.7% (NBch). The pulsatile component average of NBONH was 38.4%
      of mean NBONH; of NBch, 26.6% of the mean NBch.

PMID- 9147190
TI  - Lens epithelial cells in postoperative aqueous humor.
AB  - The aqueous humor during or after cataract surgery often contains red blood cells
      (RBCs) from blood; inflammatory cells from white blood cells (WBCs); fibrin,
      pigment cells, and fibroblasts from either the iris or the ciliary body; lens
      epithelial cells (LECs); and corneal endothelial cells. Since LECs may be related
      to postoperative complications, including a fibrin reaction and a secondary
      cataract, confirmation of their presence postoperatively not only in the capsular
      bag, but also in the aqueous humor, is necessary for identifying these
      complications. Using aqueous humor obtained from pig eyes, I attempted to
      identify LECs immunohistochemically in the aqueous humor, following
      phacoemulsification (PEA) and aspiration of the cortex, and found the presence of
      cells that react to keratin antibody, the marker for epithelial cells. Although
      these cells could be lens, conjunctival, or corneal epithelial cells, they were
      found following PEA and aspiration of the cortex, and therefore are believed to
      be LECs.

PMID- 9147191
TI  - Abducens neuropathy detected by three-dimensional magnetic resonance imaging
      using a multiplanar reconstruction technique with gadolinium-DTPA enhancement.
AB  - Three-dimensional magnetic resonance imaging (3D MRI) using a multiplanar
      reconstruction technique with gadolinium diethylenetriamine pentaacetic acid
      (DTPA) enhancement was used for assessment of a 20-year-old woman who had sudden
      complete restriction of abduction in the right eye. The 3D MRI revealed abducens
      nerve enhancement in the cisternal portion. An enhanced lesion was also observed
      in the right lower pons at the pontomedullary junction. These clinical and 3D-MRI
      findings were diagnosed as right abducens palsy due to abducens neuropathy.
      Observation of the entire pathway of the cisternal portion of the cranial nerves
      can be extremely useful in patients with ophthalmoplegia.

PMID- 9147192
TI  - Grasping the nettle--the involvement of the nurse in management decision making.

PMID- 9147193
TI  - "Becoming a mother'--developing a new theory of early motherhood.
AB  - This paper explains the methods used in a grounded theory analysis of the
      experience of 55 first-time mothers in Australia, presented in the first of this
      series of two papers. The categories identified in the research are realising,
      readiness, drained, aloneness, loss and working it out, encompassed in the core
      category becoming a mother. Specifically, this paper extends the analysis and
      explains the application of a 'paradigm model' and the identification of a Basic
      Social Process (BSP). The paper links the analysis to the literature on early
      motherhood from nursing, midwifery, feminist, and sociological research. A
      substantive theory is proposed to explain women's experience in becoming mothers
      that demonstrates how, when responsive to the needs of those researched, a
      grounded theory analysis can provide a framework for nursing and midwifery care.

PMID- 9147195
TI  - A study to ascertain gynaecological patients' perceived levels of embarrassment
      with physical and psychological care given by female and male nurses.
AB  - The Sex Discrimination Act lifted the barriers which prevented men from training
      and practising as midwives. However, cultural attitudes perceive nursing to be a
      female profession, and whilst care from a male doctor is considered to be
      acceptable, care from a male nurse is said to be embarrassing. The purpose of the
      study was to identify if there was any relationship between the intimacy of a
      nursing interaction and the patient's level of embarrassment. Data collection was
      by questionnaires with rating scales. Demographic data was obtained from nursing
      and medical notes. Statistical analysis was performed by non-parametric methods
      using Mini-tab. Ninety-one questionnaires were returned from a convenience sample
      of patients on a gynaecological oncology ward. Analysis of the data indicates
      that in a population of patients who have no prior experience of hospital
      admission, or of being cared for by a male nurse, there is a preference for care
      by a female nurse. However, this preference is not demonstrated in patients who
      have undergone previous hospital admission within the last five years or who have
      been cared for by a male nurse. These findings would indicate a cultural
      preference for care by a female nurse in patients with gynaecological cancer that
      is changed by experience during hospital admission.

PMID- 9147194
TI  - Breast self-examination: an analysis of self-reported practice.
AB  - The aim of this study was to investigate the relationship between the performance
      of breast self-examination (BSE) and age, place of residence, ethnic background
      and religion, as well as whether a group willing to take part in an interview
      regarding BSE mirrored the whole population. Six hundred and ninety-four (69.4%)
      women, aged 25-80, responded to the questionnaire. Of these, 69.6% examined their
      breasts. Whether the subjects lived in urban or rural areas was of no importance
      for practising BSE, nor was country of birth or number of years in Sweden. A
      larger proportion of women aged 45-80 practised BSE compared with women aged 25
      44 (P < 0.001), the former practising BSE once a month or more. Step-wise
      logistic regression analysis showed that, for the whole sample as well as for the
      interview group, age was the only significant predictor of breast self
      examination (P < 0.001). There were no significant differences between the whole
      sample and the interview group. The importance of younger women performing the
      examination is stressed. Due to nurses being strategically located in a wide
      range of geographical locations, allowing them to meet women in different
      settings, they are a good choice for motivating women to practise BSE.

PMID- 9147196
TI  - Family members' experiences of their role in a hospital: a pilot study.
AB  - The purpose of the study is to explore the experiences of family members in their
      role of relative in a situation where a next of kin has been admitted to
      hospital. The questionnaire was used in data collection. The data reported here
      are from a pilot study. The sample consisted of 70 family members of patients
      receiving treatment on the neurological wards. It was found that family members
      spent a lot of time at their relative's bedside, most of them up to several hours
      a day. The daily routines of families and way of life were also very much
      affected. The most important way in which the hospital supported families was to
      keep them informed about the patient's care and treatment. However, this was not
      possible without an active interest and involvement on the part of family members
      themselves. There were obvious problems and shortcomings in terms of family
      orientation: only one third of the family members felt that the nursing staff
      were seriously interested in the family's well-being, and only one quarter had
      been told what they could do in hospital. About half of the family members needed
      to meet nurses to get support from nurses and over one third from doctors. The
      oldest respondents and women needed more help than did others. Men preferred to
      turn to doctors rather than nurses for help. In general family members had good
      experiences of visiting their relative in hospital. They believed that they were
      expected and that they were of help to their relative. Over half of the family
      members said they were actively involved in caring for their relative. Only four
      per cent of the family members reported bad experiences of their visits to
      hospital, in spite of the obvious shortcomings in family nursing. For this reason
      it is important that nurses facilitate the involvement and integration of
      relatives in the process of nursing.

PMID- 9147197
TI  - The role of communication in nursing care for elderly people: a review of the
      literature.
AB  - Communication in nursing care is an important topic assessing the specific needs
      of elderly patients and providing nursing care that is tailored to the individual
      patient's needs. In this review of the literature, we describe the role
      attributed to communication in theoretical nursing models and we report how
      research in communication in nursing elderly patients has taken place over the
      last ten years. It appears that since the eighties there has been an increase in
      observation studies into nurse-patient communication. There still is, however, a
      lack of observation instruments to do justice to the interactive nature of nurse
      patient communication. Special attention should be paid to reliability and
      validity.

PMID- 9147198
TI  - Occupational need in severe dementia: a descriptive study.
AB  - This project represents the first phase of a larger study, the whole of which is
      intended to demonstrate the occupational need of elderly persons, in hospital or
      residential settings, who have severe dementia and to identify those therapeutic
      approaches which serve to meet such need. One hundred and nine severely impaired
      persons in nine dementia care units were each observed over the course of a day,
      using the dementia care mapping instrument. Results indicate a severe dearth of
      occupational provision for this client group, most of whom spent the greater part
      of their day unoccupied. They also highlight the conditions of minimum well-being
      experienced by most residents for most of the time. The anomaly of those units
      whose dementia care mapping scores did not match the perceived quality of their
      social and physical environments is discussed. A hypothesis of an altered
      perception of environment in severely impaired persons is proposed.

PMID- 9147199
TI  - A small exploratory study of the reaction of older people to an episode of
      delirium.
AB  - Delirium or an acute confusional state, occurs as a result of disease or
      physiological imbalance secondary to impaired brain function. One of its main
      clinical features is widespread cognitive impairment, which causes patients to
      become disconnected from their immediate surroundings and misinterpret reality.
      It has a sudden onset and its duration is relatively brief. Some authors take the
      view that delirium might be interpreted as a precursor to dementia. The aim of
      the study was to retrospectively explore older peoples' experience of an episode
      of delirium. In particular, whether they knew what had caused and cured it; and
      whether it had left them with any unresolved feelings of anxiety. A cross
      sectional design using grounded theory methodology was chosen, as being the most
      appropriate method for exploring this issue. A sample of 19 patients was selected
      using predetermined criteria, and engaged in a semi-structured interview with the
      researcher, in the ward environment. The interviews were audiotaped, transcribed,
      and analysed using the constant comparison method. Those interviewees who had
      illusions and hallucinations, were often able to describe their experiences in
      detail. They ranged from being pleasant and entertaining, to horrible and
      frightening. They were also able to remember short verbal commands from nurses
      during the episode of altered perception. Others remembered, or chose not to
      remember, very little. Few interviewees appeared to know exactly what had caused
      and cured the delirium, although some were able to tentatively connect the
      experience to their present medical condition. There also appeared to be little
      evidence of therapeutic communication with nursing staff once the episode of
      delirium had resolved. Although no one connected the experience with dementia,
      there did seem to be some evidence of mildly disturbed feelings, on reflecting
      back over the episode. As interviewees were generally willing to discuss their
      experiences with the researcher, it suggests that it would be helpful for nurses
      to provide opportunities to do so. Nevertheless, interviewees appeared to regard
      the episode simply as a transitory event in the overall context of illness,
      admission to hospital and their future welfare. The latter was of prime concern;
      yet again it appeared that they did not always receive the information they
      required to maintain control over their personal destinies.

PMID- 9147200
TI  - To meet with a stroke: patients' experiences and aspects seen through a screen of
      crises.
AB  - The aim of this study was to elucidate the experiences of stroke victims during
      the course of disease and the first few months after discharge. Ten individuals,
      recently having suffered their first manifest stroke with lasting neurological
      symptoms, narrated their experiences and gave their views at two different
      appointments during the first few months after discharge. A deductive approach
      was applied, on the basis of the theory of developmental crises. The analyses of
      the interviews were performed using a phenomenological hermeneutic method
      inspired by the philosophy of Ricoeur. The analyses disclosed phenomena
      signifying developmental crises in all the cases, though the crises profiles were
      marked by the sequelae the individuals suffered after stroke and by the age
      specific stages of which they were in the middle. The solution of the crises was
      from being reached within the period of data collection, as the interviews were
      performed relatively early after home-coming and the individuals were in the
      middle of grasping their new situation. The phenomenon "to meet with a stroke'
      seems to challenge the whole of the individual's being. The study calls attention
      to the need for awareness of this matter, which should be indicated to a much
      greater extent in nursing care and education than has been done until to date.

PMID- 9147201
TI  - A three-step method of self-reflection using reflective journal writing.
AB  - Fiscal and financial constraints present a challenge for nurse educators to
      broaden the diversity and scope of teaching/learning methodologies. One method
      designed to promote autonomy and self-direction of nursing students is self
      reflection combined with reflective journal writing. This paper describes a three
      step process of self-reflection encompassing critical appraisal, peer group
      discussion and self-awareness. This process of self-reflection was initiated with
      one group of clinical nursing students. Using student and teacher feedback,
      implications for employing this teaching/learning strategy in clinical practice
      are suggested.

PMID- 9147202
TI  - Nursing research: our world not theirs?
AB  - From both a theoretical and a practical standpoint the research-practice gap in
      nursing is as wide as ever. This, despite an increasing literature on the subject
      and a gamut of practical initiatives aimed at bridging the divide. This paper
      explores the two worlds of practice and research and the factors contingent on
      them. It suggests that academic researchers and practitioners have different foci
      and are working under different imperatives. These different cultures need to be
      recognised and made more explicit within current writing. The discordance between
      the worlds of research and practice forms the basis for extending the discussion
      to consider the principal conduit of research, i.e. the written word. The
      question is raised as to why research is typically reported as a seamless
      account, bereft of any information beyond details of the research process as it
      is currently legitimised within nursing ideology. Finally consideration is given
      to strategies which might facilitate the 'outing' of both researchers and their
      research.

PMID- 9147203
TI  - Integrative nursing research--an important strategy to further the development of
      nursing science and nursing practice.
AB  - In this paper it is argued that integrative nursing research has a great
      potential for clarifying the theoretical perspective and substance of the nursing
      discipline as well as making research-based knowledge more accessible to clinical
      nurses. Two general kinds of integrative research are introduced and illustration
      provided of how these have been practiced within nursing. Significant strengths
      and weaknesses in current practice is highlighted. It is argued that nursing
      should pay more attention to this kind of research, specifically in terms of
      developing sound methodological approaches and overcoming the traditional schism
      between empirical and theoretical research. Sound integrative nursing research
      promises to improve the development of nursing science as well as making the
      products of nursing research more easily available for clinical nurses.

PMID- 9147204
TI  - What do registered nurses and midwives feel and know about research?
AB  - This research is in the form of a quantitative study aimed at discovering 'What
      registered nurses and midwives feel and know about research'. Data were gathered
      on a fixed response questionnaire, with open spaces for comments to support the
      results with written factual qualitative evidence. The questionnaire was directed
      towards obtaining results associated with 'Attitudes' towards research;
      'Understandings' about research, and 'Obstacles' to implementing research. A
      sampling technique was used in which a total population of 765 registered nurses
      and midwives working in this district general hospital were involved in the
      study. The results demonstrate (inferential statistics chi-square and correlation
      tests) that registered nurses and midwives are largely in agreement with research
      based practices, although understanding about research is minimal and dependent
      on grade, length qualified, shifts and numbers of hours worked.

PMID- 9147205
TI  - Psychometric evaluation of a questionnaire to document side-effects of
      chemotherapy.
AB  - This paper reports the psychometric testing of the Worthing Chemotherapy
      Questionnaire (WCQ). The WCQ is a patient self-report instrument to document side
      effects of chemotherapy. Literature review of relevant studies shows that
      psychometric testing of similar instruments is rarely rigorous. Content validity
      for the WCQ was established in five ways: literature review, Delphi review among
      oncology staff, pre-pilot unstructured interviews, pilot study and amendment of
      the instrument and items for spontaneous reporting of problems on the
      questionnaire. A three-stage approach to construct validity was used. The
      hypothesis adopted was that as certain cytotoxic agents cause stomatitis,
      incidence and severity of stomatitis will decrease following cessation of
      treatment. Stage 1: factor analysis confirmed the presence of a sole factor, with
      an eigenvalue of 5.3, for mouth problems which explained 65.5% of the variance.
      Stage 2: the hypothesis was confirmed using research findings. Stage 3: the
      Wilcoxon test showed highly significant results for during and post chemotherapy
      stomatitis scores. Reliability of the questionnaire was assessed using the test
      retest method. Weighted kappa was chosen as the test statistic. A median value of
      wk = 0.87 was obtained. The results indicate that the WCQ is a reliable and valid
      instrument.

PMID- 9147206
TI  - Analysing clinical practice guidelines. A method of documentary analysis.
AB  - This paper will describe a method of documentary analysis used in a study
      examining the validity of clinical guidelines issued to health visitors to assist
      them in identifying families requiring increased health visitor support. This
      forms the preliminary work for a wider study examining how health visitors decide
      to increase support to vulnerable families. Although a number of published
      research texts discuss the value of records and documents as important data
      sources for health service researchers, there is relatively little information
      available about the processes of documentary analysis. This paper offers one
      method for analysing clinical practice guidelines, it describes the development
      of a critique and analysis tool and explores the strengths and weaknesses of this
      particular analysis instrument.

PMID- 9147207
TI  - The problems of researching mixed sex wards.
AB  - The following paper discusses the process of doing research on a sensitive and
      politically charged topic; 'mixed sex' psychiatric wards. It also highlights the
      conceptual and methodological difficulties of carrying out this enquiry. The
      particular deconstruction presented is suggested as knowledge or data alone, even
      though they are rarely found in finished research projects. It starts by setting
      the broader context of the research at The Bethlem and Maudsley Trust by looking
      at National policy, other studies in this subject area and media attention. It
      shows the triggers that caused a re-evaluation and changes in the original
      research question and assumptions about 'mixed sex' wards. It accounts for the
      research as it happens, rather than presenting a sanitised process of discovery.
      This forms the basis for describing some of the dilemmas for carrying out the in
      depth research; showing how the reconfigured research subject became focused on
      the safety and effectiveness of 'mixed sex' wards for women. The grounded
      methodological approach to this study is outlined and the paradoxes it identified
      in psychiatric discourse are mentioned. Exerts of findings from three separate
      research studies at The Bethlem and Maudsley Trust are given and discussed. The
      conclusion analyses the complexities of the subject and suggests that the "mixed
      sex' ward problem may be the contemporary emergence of a much older and
      fundamental problematic inherent to psychiatry. Consequently, no simple answer is
      recommended.

PMID- 9147208
TI  - Sexuality, sexual abuse. Omissions in admissions?
AB  - The main focus of this paper is to highlight the evidence relating long-term
      effects of childhood sexual abuse to presenting complaints on acute admission
      wards and to explore how sexuality, as an aspect of nursing concern, is broached
      by mental health nurses. There are few nursing articles on sexual abuse issues
      which are research-based, this literature has to be drawn from a wider field.
      Several authors recognize this paucity highlighting the need for future research
      in this area. The evidence from the literature review (1985-1995) makes it clear
      that the environment, the perceived interpersonal skills of the nurse and a
      general lack of definition of the nurse's role has a large influence on whether
      or not these issues are addressed. Following discussion about these findings,
      recommendations are made for inclusion of teaching on sexuality and sexual abuse,
      interpersonal skills training and illumination of assessment practice, with space
      for personal growth and development, in pre- and post-registration nurse
      education. This theme is developed further by considering how these
      recommendations could be introduced on acute admission wards.

PMID- 9147209
TI  - Willingness to provide care and treatment for patients with HIV/AIDS.
AB  - This paper is derived from the findings of a larger study which examines nurses'
      and doctors' attitudes towards mainstreaming of hospital inpatient services for
      individuals with HIV/AIDS in general hospital wards. The aim of this paper is to
      discuss the factors which influence nurses' and doctors' willingness to provide
      care and treatment for patients with HIV/AIDS. Two methods of study are used in
      this research--a survey questionnaire and semi-structured interviews. The
      findings of this study provide several themes about the positive attributes
      associated with caring for and treating patients with HIV/AIDS. These include:
      that caring for and treating is personally and professionally rewarding; the need
      to be non-judgemental and accepting of others; that previous work or social
      experience is related to willingness to work with patients; the influence of
      family and colleague support in the work environment; and having a duty of care.

PMID- 9147210
TI  - Assessing literacy for patient teaching: perspectives of adults with low literacy
      skills.
AB  - The purpose of this qualitative study was to gain an understanding of the
      response of English speaking adults with low literacy skills to screening of
      reading ability in order to facilitate the planning of patient teaching in a
      hospital setting. The Rapid Estimate of Literacy in Medicine (REALM) was the
      screening tool used to provide a screening experience for research subjects. A
      multiple case study design was employed to gain insight, describe participant
      experiences and generate an evidence-based conceptual model. While all
      participants supported the principle of screening in the context of the hospital,
      response to the actual experience was varied. Factors found to influence
      responses to screening included perceived risks of illiteracy exposure, perceived
      risks of non-disclosure during hospitalization and the attribution of
      characteristics to the hospital leading to it's designation as a 'special' place.
      A conceptual model of screening response was developed and compared to the Health
      Belief Model and Knox's Proficiency Theory of adult learning. Implications for
      the health professions are also discussed.

PMID- 9147212
TI  - Professional responsibility: implications for nursing practice within the realms
      of cardiothoracics.
AB  - Through an exploration of the realms of professional responsibility this paper
      aims to illustrate its implications in nursing practice with particular reference
      to the area of cardiothoracics. Throughout the paper issues surrounding the 'Code
      of Professional Conduct for the Nurse, Midwife and Health Visitor' and the 'The
      Scope of Professional Practice' released by the United Kingdom Central Council
      for Nursing, Midwifery and Health Visiting (U.K.C.C.) in 1992 are considered.
      'The Code' as it will subsequently be referred to, and the 'The Scope of
      Professional Practice' (U.K.C.C.) address issues of current change within the
      nursing profession and provide a focus for discussion. While recognising both
      current constraints to clinical practice and the complexity of professional
      responsibility, it is concluded that the delivery of research based, quality
      patient care remains central to the role of all nursing professionals. With a
      primary focus on others before the self, nursing professionals must continue to
      address issues surrounding the maintenance and development of this care.

PMID- 9147211
TI  - A conceptual foundation for human suffering in nursing care and research.
AB  - Suffering is a significant, yet elusive, phenomenon in nursing and health care.
      Despite the importance and prevalence of suffering, there is only a small body of
      substantive literature on this topic. Some of the difficulty in expanding this
      knowledge base undoubtedly is related to the lack of a solid conceptual
      foundation for exploration of this phenomenon. Although there have been attempts
      to provide needed conceptual clarity, these efforts typically have not been based
      on systematic inquiry. In this study, the method of concept analysis was used to
      inductively generate a definition of the concept of suffering and to clarify
      various contextual aspects of the concept. Suffering is defined as an
      individualized, subjective, and complex experience that involves the assignment
      of an intensely negative meaning to an event or a perceived threat. Implications
      of these findings and additional contextual aspects of the concept for nursing
      practice and inquiry are presented. These results help to provide the conceptual
      foundation needed to enhance recognition and understanding of the human
      experience of suffering.

PMID- 9147214
TI  - Science, abduction and the fuzzy nurse: an exploration of expertise.
AB  - Benner's work on expertise in nursing drew heavily on the writing of Dreyfus and
      Dreyfus in the field of computing. Dreyfus and Dreyfus argued that the continued
      failure of computer programmers to create an 'expert system', a program which
      could replicate the way that a human expert thinks, implied that experts do not
      think in a rational, analytic way. Dreyfus and Dreyfus therefore concluded that
      expertise is an intuitive process, and that 'the expert is simply not following
      any rules! He is ... recognising thousands of special cases'. Applied to nursing,
      this model of expertise has a number of profound implications for practice and
      education, and has been criticised for being elitist and deliberately obscure.
      This paper examines some recent innovations in computer logic, and argues that
      nursing can learn from a new breed of 'fuzzy' computer programmes which appear to
      be able not only to perform better than experts, but to verbalize their decision
      making processes. By beginning to understand how experts think, it might be
      possible to develop expertise in a more controlled and logical way, thereby
      improving the practice of nursing.

PMID- 9147213
TI  - The theory-practice relationship in nursing: an exploration of contemporary
      discourse.
AB  - The nature of nursing practice, the nature and origins of nursing theory and the
      issue of the relationship between theory and practice are matters which have and
      continue to generate extensive philosophical discourse within nursing. Despite
      the abundance of literature on these matters, to date there have been few
      attempts to bring together, to summarise and to characterise the various ways in
      which the theory-practice relationship is understood within nursing. This paper
      offers a description of the principal ways in which the theory-practice
      relationship is commonly understood within contemporary philosophical discourse.
      An exploration of contemporary, scholarly discourse within the nursing
      literature, using Carr's typology of theories of theory and practice, as a
      framework for analysis, points to evidence that the theory-practice relationship
      is understood in a number of different ways. Foremost among these is the tendency
      to think of nursing as an applied-science and there is a tendency to think of
      theory and practice as separate endeavours. The content of the discourse also
      points to a tendency to view the relationship as one in which the basis for
      practice lies in the collective 'common-sense' understandings of practitioners
      engaged in practice. The relationship is also understood in terms of nursing
      being an 'ethical' activity in which practical wisdom, deliberation, judgements
      and choices are required for the conduct of practice. There is, in more recent
      discourse, evidence of views which attempt to contextualise nursing within its
      social reality and thus to conceive of the theory-practice relationship in ways
      congruent with the recognition that nursing practice is a human and a social
      enterprise that is inherently 'problematic'. These contemporary
      conceptualizations of the theory-practice relationship would appear to have
      evolved through a process in which each new conception has been accommodated with
      and assimilated into the already existing understandings. Ways of viewing the
      theory-practice relationship are expressed either explicitly or, in many
      instances, are implicit in and recoverable from expressions of views, beliefs and
      assumptions. It would appear that the current state of thinking with respect to
      the theory-practice relationship is one of eclecticism and pluralism and there is
      a general openness to the contribution of different paradigms of knowing to
      epistemological development.

PMID- 9147215
TI  - Supportive learning in distance education.
AB  - This paper argues that tutorial support should enhance the learning experience of
      students who enrol on a distance education programme. A rationale for such
      support is given as well as a definition of support for distance learners. The
      complex role of the tutor in distance learning is described which suggests the
      need for tutor preparation, particularly for tutors adapting to this mode of
      course delivery. The paper reports on two existing models used within distance
      education which have focused on the outcome of study. The paper introduces an
      alternative model of supportive learning which focuses on the development of the
      educational experience throughout the length of a distance-learning course.

PMID- 9147216
TI  - Power and vested interests--tacit influences on the construction of nursing
      curricula?
AB  - Educational reform and the introduction of Project 2000 has presented an
      opportunity to construct broader curricula with the intention of educating
      adaptive, critical practitioners who are able to deliver holistic patient care.
      Evidence within nursing literature, and from a small-scale descriptive research
      study (N = 38), suggests that there is a lack of consensus about how knowledge
      from various cognate disciplines should be emphasised and structured within
      nursing curricula. Findings from the research study suggest that the emphasis
      placed on different cognate disciplines within nursing curricula may reflect
      individuals' vested interests and power. A conceptual framework based upon the
      sociology of knowledge, and conflicts and tensions between groups within a
      profession, is presented as a construct which lends support to this suggestion.
      It is hoped that this paper will stimulate reflection and critical debate about
      how knowledge from a variety of cognate disciplines is selected and emphasised in
      the construction of nursing curricula.

PMID- 9147217
TI  - What is philosophy of nursing?
AB  - This paper tries to describe the nature of the subject-area known as philosophy
      of nursing. It is suggested that attempts to offer such a description are beset
      with difficulties surrounding both nurses' and philosophers' conception of
      philosophy. Nonetheless, this paper does seek to offer a description of what
      philosophy amounts to. Schrock's suggestion that philosophy can be characterised
      partly by its methods and the distinctive nature of its questions is tentatively
      endorsed. Her proposal is buttressed with an account of Carnap's distinction
      between internal and external questions. It is shown that this distinction helps
      to identify philosophical questions. Further, an attempt is made to show the
      importance of the distinction between a philosophy of nursing and philosophy of
      nursing. It is concluded that philosophy involves conceptual analysis and
      assessment of argument, concern with highly general metaphysical and
      epistemological questions, and that such questions can be regarded as 'external'
      questions. It is then shown how these three elements of philosophy also
      characterise philosophy of nursing.

PMID- 9147218
TI  - The professional imagination: narrative and the symbolic boundaries between
      medicine and nursing.
AB  - The sociology of nursing, despite decisive interventions by recent commentators,
      continues to take as its main focus the subordination of nursing to biomedicine.
      This view reflects analytic stability, as well as institutional inertia. Far less
      attention has been paid by sociologists to the ways in which nursing is
      constructing its difference from medicine, and the exercise of the professional
      imagination that this involves. This paper suggests a strategy by which this
      might be remedied, which would focus on professional narratives.

PMID- 9147219
TI  - Catecholaminergic innervation of interscapular brown adipose tissue in the naked
      mole-rat (Heterocephalus glaber).
AB  - The thermogenic potential of the interscapular brown fat pad in the naked mole
      rat Heterocephalus glaber, that exhibits poikilothermic thermal responses to
      changing temperatures is reported. Histological and ultrastructural study of the
      brown fat pad showed that it consists of layers of skeletal muscle interposed
      between the layers of brown adipose tissue with both unilocular and multilocular
      adipocytes. Large numbers of mitochondria were present between and around the
      lipid droplets of these cells. Glyoxylic acid condensation, used to demonstrate
      catecholaminergic nerves, was evident in low concentrations in the connective
      tissue between the brown adipocytes. A 3-dimensional computer-aided
      reconstruction of the fat pad showed the extent and ramification of nerves and
      blood vessels between the adipocytes. These findings show that although the naked
      mole-rat is regarded as an endothermic poikilotherm, it possesses anatomical
      features usually found in homeothermic mammals, which are essential for
      thermogenesis.

PMID- 9147220
TI  - Fetal and postnatal development of the patella, patellar tendon and suprapatella
      in the rabbit; changes in the distribution of the fibrillar collagens.
AB  - The development of the patella, its associated tendons, and suprapatella of the
      rabbit knee joint is described from the 17 d fetus to the mature adult. The
      patellar tendon (ligament) with the patella on its posterior surface is seen in
      the 17 d fetus and is fully developed by 1 postnatal wk. It is composed of
      bundles of types I and V collagens separated by endotenons of types III and V
      collagens. Anteriorly there is an epitenon of types III and V collagens while
      synovium and a fat pad cover its posterior surface. In the 25 d fetus, the
      patella is cartilaginous and is separated from the femoral condyles. The
      cartilage contains type II collagen, but types I, III and V collagens are found
      along the articular surface. Ossification starts 1 postnatal wk and at 6 wk only
      the articular cartilage remains. In addition to type II, types III and V
      collagens are located around the chondrocyte lacunae. The long anterior junction
      between the patella and its tendon is fibrocartilaginous at 1 wk, but as
      ossification proceeds this is replaced by bone. Types I and V collagens are found
      in this region. The suprapatella on the posterior surface of the quadriceps
      tendon is first seen 1 wk postnatally as an area of irregularly organised fibres
      and chondrocyte-like cells. Types I, II, III and V collagens are present from 3
      wk onwards. It is compared with the fibrocartilage of other tendons that are
      under compression. The arrangement of the collagens in the patellar tendon is
      discussed in relation to its use as a replacement for injured anterior cruciate
      ligaments. It is suggested that the structural differences between the patellar
      tendon and anterior cruciate ligament preclude the translocated tendon acquiring
      mechanical strength similar to that of a normal cruciate ligament. The
      designation 'patellar ligament' as opposed to 'patellar tendon' is questioned. It
      is argued that the term patellar tendon reflects its structure more accurately
      than patellar ligament.

PMID- 9147221
TI  - Immunohistochemistry of a prostate membrane specific protein during development
      and maturation of the human prostate.
AB  - An antiserum against secretory vesicles from human seminal fluid (prostasomes)
      was used to study the localisation and distribution of the respective antigen(s)
      during prenatal development and pubertal maturation of the human prostate. The
      crude antiserum stained both secretory and membrane proteins in the adult
      prostate and other glands, such as pancreas and parotid gland. An immunoaffinity
      purified fraction from the antiserum selectively reacted with the apical plasma
      membrane of prostatic epithelium adluminal cells, recognizing a 100 kDa antigen
      (PMS). Even in the earliest stages of embryonic prostate specimens studied, the
      adluminal plasma membrane of the epithelial cells from developing glandular
      anlagen reacted strongly. The occurrence of PMS immunoreactivity in prostatic
      anlagen was directly correlated with lumen formation. As the antigen is an
      androgen-independently synthesised membrane protein of the prostate, it may
      possibly be used as a marker of cell polarity in the normal and pathologically
      altered prostate.

PMID- 9147224
TI  - Spermiogenesis and spermiation in a marsupial, the tammar wallaby (Macropus
      eugenii).
AB  - Fourteen steps of spermatid development in the tammar wallaby (Macropus eugenii),
      from the newly formed spermatid to the release of the spermatozoon into the lumen
      of the seminiferous tubules, were recognised at the ultrastructural level using
      transmission and scanning electron microscopy. This study confirmed that although
      the main events are generally similar, the process of the differentiation of the
      spermatid in marsupials is notably different and relatively more complex than
      that in most studied eutherian mammals and birds. For example, the sperm head
      rotated twice in the late stage of spermiogenesis: the shape of the spermatid
      changed from a T-shape at step 10 into a streamlined shape in step 14, and then
      back to T-shape in the testicular spermatozoa. Some unique figures occurring
      during the spermiogenesis in other marsupial species, such as the presence of
      Sertoli cell spurs, the nuclear ring and the subacrosomal space, were also found
      in the tammar wallaby. However, an important new finding of this study was the
      development of the postacrosome complex (PAC), a special structure that was first
      evident as a line of electron dense material on the nuclear membrane of the step
      7 spermatid. Subsequently it became a discontinuous line of electron particles,
      and migrated from the ventral side of the nucleus to the area just behind the
      posterior end of the acrosome, which was closely located to the sperm-egg fusion
      site proposed for Monodelphis domestica (Taggart et al. 1993). The PAC and its
      possible role in both American and Australian marsupials requires detailed
      examination. Distinct immature features were discovered in the wallaby testicular
      spermatozoa. A scoop shape of the acrosome was found on the testicular
      spermatozoa of the tammar wallaby, which was completely different to the compact
      button shape of acrosome in ejaculated spermatozoa. The fibre network found
      beneath the cytoplasm membrane of the midpiece of the ejaculated sperm also did
      not occur in the testicular spermatozoa, although the structure of the principle
      piece was fully formed and had no obvious morphological difference from that of
      the epididymal and ejaculated spermatozoa. The time frame of the formation of
      morphologically mature spermatozoa in the epididymis of the tammar wallaby needs
      to be determined by further studies.

PMID- 9147222
TI  - The effects of ageing on wound healing: immunolocalisation of growth factors and
      their receptors in a murine incisional model.
AB  - A number of reports suggest that the process of ageing impairs wound repair and
      that strategies to manipulate the age-related wound healing environment are
      necessary in order to stimulate repair. The process of cutaneous wound repair is
      controlled by growth factors in an autocrine and paracrine fashion: it is
      therefore surprising that the localisation of specific growth factors and their
      receptors has not been documented in wound healing with respect to chronological
      age. In this study the temporal profile of growth factor and receptor
      immunostaining was assessed within acute incisional wounds in an ageing mouse
      colony. A delay in appearance of platelet derived growth factor (PDGF) A and B
      isoforms, and PDGF-alpha and -beta receptors was evident with increasing animal
      age, paralleled by a similar finding for epidermal growth factor (EGF) and EGF
      receptor. Transforming growth factor (TGF)-beta 1 and 2 isoforms were increased
      at all time points in the wounds of younger animals, but the TGF-beta 3 isoform
      increased in intensity from d 7 postwounding in the old mice wounds, and basic
      fibroblast growth factor (bFGF) from d 14. The quantity and distribution patterns
      of the various growth factors and their receptors may explain the age-related
      differences in wound healing speed and quality, and possibly suggest new
      therapeutic targets for manipulating wound healing in the aged.

PMID- 9147223
TI  - The distribution of trigeminovascular afferents in the nonhuman primate brain
      Macaca nemestrina: a c-fos immunocytochemical study.
AB  - An understanding of migraine must be based on data concerning the anatomy and
      physiology of the painsensitive intracranial structures. Stimulation of the
      superior sagittal sinus produces changes in brain blood flow and changes in
      neuropeptide levels similar to those seen in humans during migraine. To better
      understand the anatomy of the central ramifications of pain-sensitive
      intracranial structures we have examined the distribution of c-fos
      immunoreactivity in the monkey when the sinus is stimulated. Six adult Macaca
      nemestrina monkeys were anaesthetised. The superior sagittal sinus was isolated
      after a midline craniotomy and a paraffin well created. At 24 h after completion
      of the surgery the sinus was stimulated electrically for 1 h and the brain
      subsequently removed and processed for c-fos. In control animals in which the
      sinus was isolated but not stimulated there was a small amount of c-fos
      expression in the caudal brainstem and upper cervical spinal cord. Stimulation of
      the superior sagittal sinus evoked expression of c-fos in the caudal superfical
      laminae of the trigeminal nucleus and in superficial laminae of the dorsal horn
      of the C1 level of the upper cervical spinal cord. A lesser amount of c-fos was
      seen at C2 while no significant labelling above control was observed at C3. These
      data, while largely confirming the results from the cat concerning the central
      distribution trigeminovascular afferents, underscore a possibly unique
      specialisation of trigeminovascular afferents at the C1 level. Given the close
      evolutionary relationship of the monkey to man it is likely that the cells
      described in this study represent for primates the nucleus that mediates the pain
      of migraine.

PMID- 9147225
TI  - An immunocytochemical study of changes in the human erythrocyte membrane skeleton
      produced by stretching examined by the quick-freezing and deep-etching method.
AB  - A quick-freezing and deep-etching method in combination with erythrocyte
      splitting was used to examine the cytoplasmic aspect of whole-mount human
      erythrocyte membranes. Various external forces induced alterations in membrane
      skeletal organisation during the splitting procedure. The initial change was
      elongation in the peripheral part of the membrane skeleton, examined by
      immunostaining with a monoclonal antispectrin antibody. Under severe stretching
      conditions, a linear rearrangement of filamentous components was evident; these
      were disposed parallel to the rim of the erythrocyte, while the central part of
      the concavity exhibited a more compacted structure. These changes resulted in a
      different distribution of membrane skeletal components between central rigid and
      peripheral flexible areas in biconcave erythrocytes. It is suggested that the
      reversible membrane skeletal changes in the flexible areas which resist the
      external forces are important for maintaining the normal framework of biconcave
      human erythrocytes.

PMID- 9147226
TI  - Involution of the sheep mammary gland.
AB  - Changes in the ovine mammary gland epithelium during initiated involution were
      studied by light and electron microscopy. Apoptosis of the duct and alveolar
      epithelial cells was first identified at 2 d after weaning, reached a peak at 4 d
      and then progressed gradually thereafter. Apoptotic cells were phagocytosed by
      intraepithelial macrophages and alveolar epithelial cells. Occasional apoptotic
      epithelial cells were observed in the alveolar and duct lumina. The highly
      vacuolated cells in the alveolar and duct lumina were confirmed to be macrophages
      as they were CD45+, MHC class II+. Changes in myoepithelial cells involved
      shrinkage and extension of cytoplasmic processes into the underlying stroma and
      no apoptosis was observed. Regression of the blood capillaries was also by
      apoptosis. The resulting apoptotic bodies were either taken up by adjacent
      endothelial cells or were shed into the capillary lumen to be phagocytosed later
      by mural endothelial cells or blood monocytes. The mammary glands were completely
      involuted by 30 d after weaning. It was concluded that the mammary gland
      involutes by apoptosis, a process which allows deletion of cells without the loss
      of the basic architecture and the integrity of the epithelial lining of the
      gland.

PMID- 9147227
TI  - Production of consistent crush lesions of murine skeletal muscle in vivo using an
      electromechanical device.
AB  - The crush model of injury in skeletal muscle is widely used in the investigation
      of tissue degeneration and regeneration. Previously, such trauma has been induced
      by using forceps to crush the muscle, commonly applying sufficient pressure to
      bring the mid-arms of the forceps together. This report introduces a reliable
      electromechanical device designed to generate reproducible focal lesions in
      skeletal muscle of mice. The tibialis anterior was crushed in 17 young adult
      mice. Two days after injury, the muscles were examined microscopically. By
      morphometric analysis, it was determined that the volumes of the lesions produced
      were similar (mean 0.499 mm3 +/- 0.098, range 0.278 - 0.601 mm3), and that the
      full extent of the damaged muscle was easily distinguished and readily
      quantifiable. This will allow a more precise comparison in future investigations
      into regenerative differences between age groups, satellite cell activation and
      the inflammatory response.

PMID- 9147228
TI  - Abnormal Schwann cell/axon interactions in the Trembler-J mouse.
AB  - The Trembler-J (TrJ) mouse has a point mutation in the gene coding for peripheral
      myelin protein 22 (PMP22). Disturbances in PMP22 are associated with abnormal
      myelination in a range of inherited peripheral neuropathies both in mice and
      humans. PMP22 is produced mainly by Schwann cells in the peripheral nervous
      system where it is localised to compact myelin. The function of PMP22 is unclear
      but its low abundance (approximately 5% of total myelin protein) means that it is
      unlikely to play a structural role. Its inclusion in a recently discovered family
      of proteins suggests a function in cell proliferation/differentiation and
      possibly in adhesion. Nerves from TrJ and the allelic Trembler (Tr) mouse are
      characterised by abnormally thin myelin for the size of the axon and an increased
      number of Schwann cells. We report ultrastructural evidence of abnormal Schwann
      cell-axon interactions. Schwann cell nuclei have been found adjacent to the nodes
      of Ranvier whereas in normal animals they are located near the centre of the
      internodes. In some fibres the terminal myelin loops faced outwards into the
      extracellular space instead of turning inwards and terminating on the axon. In
      severely affected nerves many axons were only partially surrounded by Schwann
      cell cytoplasm. All these features suggest a failure of Schwann cell-axon
      recognition or interaction. In addition to abnormalities related to abnormal
      myelination there was significant axonal loss in the dorsal roots.

PMID- 9147230
TI  - On the morphology of the brachial plexus of the platypus (Ornithorhynchus
      anatinus) and the echidna (Tachyglossus aculeatus).
AB  - Four forelimbs of 3 platypuses and 3 forelimbs of 2 echidnas were examined to
      study the precise form of the brachial plexus and to clarify the structural
      characteristics of the brachial plexus in phylogeny. The spinal components
      contributing to the plexus (C4-T2) and the formation patterns of the 3 trunks of
      the plexus were the same as those generally observed in mammals. In the cranial
      half of the brachial plexus from C4, 5 and 6 in monotremes, division into the
      ventral bundle (lateral cord) and dorsal bundle (axillary nerve) is clear, as in
      other mammals. However, for monotremes, in the caudal half of the plexus from C7
      and T1 (+T2) and the nerves arising from the caudal plexus there is no definite
      division into the ventral and dorsal bundles, which distribute to the flexor and
      extensor parts of the forelimbs, respectively. The lower trunk of the monotreme
      brachial plexus forms a cord which contains both ventral and dorsal components.
      This characteristic diverges from the generally accepted idea that the tetrapod
      limb plexus is divided clearly into 2 layers: a dorsal layer for extensors and a
      ventral layer for flexors of the limb. Considering the incomplete dorsoventral
      division of forelimb nerves in some reptiles and urodeles, the caudal half of the
      monotreme brachial plexus has characteristics in common with those of lower
      tetrapods.

PMID- 9147229
TI  - Ultrastructure of quick-frozen and freeze-substituted chick osteoclasts.
AB  - For comparison with chemically fixed osteoclasts, we prepared chick osteoclasts
      by quick freezing followed by freeze-substitution. In spite of technical
      difficulties this demonstrated that osteoclasts can be satisfactorily frozen in
      situ by the metal contact method. Ultrastructural differences were revealed
      between conventional fixation and quick freezing. Compared with conventional
      fixation, the quick freezing method appeared to improve preservation: (1) a
      discrete trilaminar plasma membrane and other intracellular membranes showed a
      smooth profile without undulation or rupture; (2) cytoskeletal components
      appeared to be clearer, straighter, and more numerous; (3) the interior of the
      ruffled finger contained interconnected lattice structures whereas highly
      organised microfilaments were seen in the clear zone; (4) well developed
      tubulovesicular structures (TVSs) that branched or anastomosed with each other
      were revealed in the cytoplasm; (5) the contents of intracellular membrane
      systems including the nuclear envelope, endoplasmic reticulum, and Golgi complex
      were stained to a various extent; (6) vesicles and vacuoles were much smaller,
      round and well-defined with electron-dense contents; (7) crystalline structures
      were seen at the extracellular channels of the ruffled border, in the lumen of
      TVSs, and in vesicles; (8) in some instances mitochondrial granules were visible;
      (9) within the resorptive lacuna, osteoclasts adhered to the degraded bone matrix
      without any intervening empty space.

PMID- 9147231
TI  - The glenoid notch and its relation to the shape of the glenoid cavity of the
      scapula.
AB  - The prevalence of a notch in the anterior margin of the glenoid cavity of 236
      scapulae (118 female, 118 male) was investigated. The notch was found in 129
      scapulae (55%) and gave rise to a pear-shaped cavity. In 107 scapulae (45%) the
      notch was absent, the shape of the cavity being oval. No sex difference was found
      in the prevalence of the notch. If a distinct notch exists, the glenoid labrum is
      not attached to bone at the notch and is therefore liable to be sheared off
      (Bankart lesion).

PMID- 9147232
TI  - Changes in the surface of the superior articular joint from the lower thoracic to
      the upper lumbar vertebrae.
AB  - Thirty-two human vertebral columns were selected from the Kanazawa Collection at
      the University of Kanazawa, Japan. The superior articular joint surface was
      categorised into the thoracic type and the lumbar type, and the pattern of the
      change from one type to the other in the lower thoracic and upper lumbar region
      was examined. In 21 of 32 cases (66%), the change from the thoracic to the lumbar
      type occurred over 2 vertebral segments, either between the 12th thoracic and 1st
      lumbar vertebrae (44%) or between the 11th and 12th thoracic vertebrae (22%). In
      the remaining 11 cases (34%), the change occurred over 3 vertebral segments, with
      a transitional type of articular surface. The change from the thoracic to lumbar
      type of articular surface has been believed to occur over 2 vertebral segments,
      but occurs over 3 segments in as many as 34% of the articular surfaces.

PMID- 9147233
TI  - The intramuscular arterial anatomy of the long head of biceps femoris muscle.
AB  - We have previously shown that the neurovascular anatomy and length of the long
      head of biceps femoris (LHBF) is suitable for its possible use in the creation of
      a dynamic perianal myoplasty to restore faecal continence. If intramuscular
      arterioarterial anastomoses exist between a muscle's vascular pedicles then the
      delay procedure, i.e. ligating the vascular pedicles to the transposed section of
      the muscle, 4-6 wk before transposition, can be used to improve blood flow to the
      distal part of the transposed muscle. The intramuscular arterial anatomy of 20
      biceps femoris muscles was shown by dissection (14) or radiographically (6). The
      mean entry point of the upper major vascular pedicle to the LHBF was 12 cm (S.D.
      3.3) and the mean length of the LHBF was 36.8 cm (S.D. 1.8). Therefore the ratio
      between upper major vascular pedicle entry point and muscle length in 95% of
      specimens was 0.33 (0.2). In the present study intramuscular arterioarterial
      anastomoses were found between the arterial pedicles to the nontransposed and
      transposed sections of the LHBF and between the long and short heads of this
      muscle. Using the delay procedure would therefore theoretically allow the
      intramuscular arterioarterial anastomoses between the arterial pedicle to the
      nontransposed and transposed sections of the LHBF to open up enhancing blood flow
      to the distal part of the myoplasty.

PMID- 9147234
TI  - An update on the identity of early pregnancy factor and its role in early
      pregnancy.

PMID- 9147236
TI  - Embryo developmental stage at transfer influences outcome of treatment with
      intracytoplasmic sperm injection.
AB  - PURPOSE: Our purpose was to determine if embryo cell stage at the time of
      intrauterine transfer correlates with pregnancy rate in patients treated with
      intracytoplasmic sperm injection (ICSI). METHODS: We conducted a retrospective
      analysis of 455 embryo transfer cycles following ICSI and 304 conventional in
      vitro fertilization (IVF) and embryo transfer cycles in women aged 40 years or
      less. Abstracted information included grading of the embryo cell stage and
      quality at the time of transfer. RESULTS: The overall ICSI pregnancy rate was
      30.8%, while that of conventional IVF was 29.3%. However, the ICSI pregnancy rate
      fell to 9.3% for embryo transfers taking place at the two-cell stage but
      increased to 35.8% when at least one embryo had more than two cells, and this
      difference was statistically significant (P < or = 0.0001). The pregnancy rate
      following conventional IVF was 22.0% when only two-cell embryos were transferred
      and 32.0% when at least one of the embryos had more than two cells, but this
      difference in pregnancy rates was not significant (P > 0.05). CONCLUSIONS: The
      stage of embryo development at transfer appears to exert a powerful influence on
      the successful establishment of pregnancy after ICSI.

PMID- 9147235
TI  - Features of the Renin-angiotensin system in ascites and pleural effusion during
      severe ovarian hyperstimulation syndrome.
AB  - PURPOSE: The purpose of this work was to investigate the ovarian renin
      angiotensin system (RAS) during severe ovarian hyperstimulation syndrome (OHSS)
      with ascites and pleural effusion. METHODS: Two patients who developed severe
      OHSS after ovarian stimulation for in vitro fertilization were investigated. Both
      patients presented ascites and pleural effusion. Blood, ascites, and pleural
      fluid were simultaneously sampled during therapeutic paracentesis and
      thoracocentesis. Renin activity, active renin, prorenin, and angiotensin II
      immunoreactivity (Ang II-ir) were measured simultaneously in plasma, ascites, and
      pleural fluid. RESULTS: Prorenin, renin activity, active renin, and Ang II-ir
      levels were much higher than normal plasmatic laboratory norms in the three
      compartments. Prorenin and Ang II-ir levels were the highest in the ascites,
      while they were in the same range in the pleural fluid and in the plasma.
      CONCLUSIONS: The present findings provide additional evidence for the ovarian
      origin of the prorenin and Ang II-ir in the ascites of severe OHSS.

PMID- 9147237
TI  - Comparison of the role of cervical and intrauterine insemination techniques on
      the incidence of multiple pregnancy after artificial insemination with donor
      sperm.
AB  - PURPOSE: Our purpose was to investigate the role of the insemination technique
      used in an artificial insemination program with donor sperm (AID) in multiple
      pregnancy rates. METHODS: We carried out a retrospective nonrandom analysis of
      300 pregnancies corresponding to 300 cycles in women from our Artificial
      Insemination Donor Sperm Program. All cycles were stimulated with gonadotropins.
      Single and multiple pregnancy cycles and intracervical and intrauterine pregnant
      cycles were compared. RESULTS: Intracervical insemination was performed in 173
      cycles (58%), and intrauterine insemination in 127 (42%). Two hundred twenty
      three pregnancies were single (74%), and 77 multiple (26%). In multiple pregnancy
      cycles, initial dose and mean total daily dose of gonadotropins, plasma estradiol
      levels, and number of follicles > or = 14 mm were significantly higher compared
      to those in single pregnancy cycles. Multiple pregnancy rte was significantly
      higher among pregnancies after intrauterine insemination (32%) than after
      intracervical insemination (21%). CONCLUSIONS: The intrauterine technique of
      insemination in AID-stimulated cycles with gonadotropins is related to multiple
      pregnancy risk.

PMID- 9147238
TI  - Oocyte quality in polycystic ovaries revisited: identification of a particular
      subgroup of women.
AB  - PURPOSE: Our purpose was to assess the endocrine status of women with polycystic
      ovaries (PCO) undergoing IVF, and to compare oocyte quality with endocrine
      markers of the syndrome, in an attempt to define a subpopulation with poor
      quality oocytes. METHODS: This was a retrospective study. Patients were first
      endocrinologically analyzed: serum levels of androgens (T, androstenedione,
      DHEAS), FSH, and LH as well as glucose and insulin after an oral glucose
      tolerance test (OGTT) were recorded and are expressed as absolute values and area
      under the curve (AUC). Subsequently, they were followed over a 2-year period in
      which patients underwent several attempts of IVF as well as serving as oocyte
      donors. Patients were divided into three groups: group I (n = 4) was women who
      displayed embryos unable to implant in 15 IVF cycles and 10 ovum donation cycles
      in which they served as donors; group II (n = 16) was PCO patients in whom IVF (n
      = 38) and/or oocyte donation cycles (n = 42) resulted in pregnancies; and group
      III (n = 13) was IVF patients with normal appearance of the ovaries by
      ultrasound. The endocrine status was compared with the IVF results. RESULTS:
      There was no difference among groups in the endocrinological parameters tested,
      except for the OGTT which identified women in group I as having higher serum
      glucose and insulin levels than patients in groups II and III. Similarly, the
      OGTT showed higher serum glucose values in group II compared to group III. Women
      in group I were also obese. Patients in group III were older than PCO patients
      and needed more gonadotropins to reach an ovarian response which resulted in a
      reduced number of oocytes retrieved. Fertilization was also impaired in group I,
      in which no pregnancy was recorded. CONCLUSIONS: This study shows that there is a
      particular subgroup of PCO patients with lower fertilization rates and embryos
      unable to implant. These patients are obese and nonhyperandrogenic and show
      derangements of insulin secretion.

PMID- 9147239
TI  - Expression of transforming growth factor alpha (TGF-alpha) gene in mouse
      embryonic development.
AB  - PURPOSE: The expression of genes for TGF-alpha, epidermal growth factor (EGF),
      and the EGF receptor (EGFR) in mouse blastocysts was evaluated by the reverse
      transcription-polymerase chain reaction (RT-PCR). We evaluated the effects of TGF
      alpha and EGF on the development of mouse embryo prior to implantation. RESULTS:
      The results revealed the presence of transcripts of TGF-alpha and EGFR. However,
      EGF mRNA was not observed in repeated experiments. None of these growth factors
      influenced the rate of development from the two-cell stage to the blastocyst
      stage when added to the culture medium. These effects were further examined on
      measuring the incorporation of tritiated thymidine and leucine, providing indices
      of the synthesis of DNA and protein, respectively. A concentration of only 0.1
      ng/ml of TGF-alpha, which shares a cell surface receptor with EGF, stimulated the
      synthesis of both DNA and protein. EGF at a concentration of 10 ng/ml stimulated
      the synthesis of DNA and protein by blastocysts. To explore autocrine effects of
      TGF-alpha on the rate of blastocoel expansion, TGF-alpha antisense
      oligodeoxynucleotides was used to reduce expression of the TGF-alpha gene. TGF
      alpha at a concentration of 0.1 ng/ml stimulates the rate of blastocoel expansion
      in early cavitating mouse blastocysts. In contrast, TGF-alpha antisense
      oligonucleotides significantly reduced the rate of expansion. CONCLUSIONS: Our
      present observations suggest that TGF-alpha/EGF and the EGFR may be involved in
      regulating embryonic development. In particular, TGF-alpha may serve as an
      autocrine factor in the regulation of embryonic development.

PMID- 9147240
TI  - Effect of androgen substrates on the steroidogenic pattern of cumulus cells:
      correlation with cumulus culture morphology.
AB  - BACKGROUND: In previous studies, higher progesterone secretion was observed in
      mature versus immature cumulusoocyte complexes. In mature cumulus mass that
      become homogeneously spread in culture (type C/D) progesterone secretion was
      higher than in partially (type B) or totally (type A) aggregated morphology. In
      sharp contrast, estradiol-17 beta secretion was significantly higher in type A
      than type C/D cumulus. PURPOSE: Our purpose was to assess whether the decreased
      estradiol-17 beta level in type C/D cumulus culture is caused by deficiency of
      substrates. METHODS: The different cumulus types were incubated with or without
      10(-7) M dehydroepiandrosterone, 4-androstane-3, 17-dione, or testosterone. The
      levels of estradiol-17 beta, testosterone, and progesterone, were measured after
      24 hr of culture. RESULTS: The addition of dehydroepiandrosterone or 4-androstane
      3, 17-dione significantly increased the estradiol-17 beta levels in all types of
      cumulus cells, whereas the addition of testosterone was less effective. In all
      types of cumulus cells the testosterone levels increased significantly on adding
      these androgen substrates. In the type C/D cumulus, the testosterone increased to
      lower levels compared to type A cumulus cells. In the presence of these androgens
      progesterone secretion is significantly reduced in type A cumulus cells. In type
      C/D cumulus cells, however, progesterone levels were significantly higher than in
      type A. The estradiol-17 beta/ testosterone and progesterone/estradiol-17 beta
      ratios, which partially resemble the degree of aromatase activity and the degree
      of selectivity for progesterone secretion, respectively, were higher in type C/D
      than in type A cumulus cells. CONCLUSIONS: In type C/D cumulus the significant
      increase in estradiol-17 beta secretion in the presence of various androgens
      suggests that, under basal conditions, androgen is less available for estradiol
      17 beta biosynthesis compared to type A cumulus. Furthermore, the higher
      progesterone secretion in type C/D cumulus may suggest that the follicles
      yielding type C/D cumulus cells are more mature than the follicles yielding type
      A cumulus.

PMID- 9147241
TI  - Effects of sperm viability on fertilization and embryo cleavage following
      intracytoplasmic sperm injection.
AB  - PURPOSE: In the human, intracytoplasmic sperm injection is typically performed
      using "viable" sperm which has been mechanically rendered nonmotile. The purpose
      of the present study was to determine the ability of nonviable sperm to fertilize
      human oocytes and the early developmental normalcy of the resulting embryos.
      METHODS: In this study, immature, prophase I oocytes from a total of 27
      consenting patients were matured in vitro and then randomized into two groups:
      injection with a viable human sperm or injection with a sperm rendered nonviable
      by freeze-thawing in liquid nitrogen. The rates of fertilization and cleavage
      were compared between the two groups. RESULTS: The results demonstrated a
      significantly higher two-pronuclear fertilization rate when oocytes were injected
      with viable sperm (62.2%) compared to when oocytes were injected with nonviable
      sperm (16.2%). Oocytes injected with viable sperm also demonstrated a higher
      cleavage rate (91 vs 33%). CONCLUSIONS: These findings suggest that while the
      intracytoplasmic injection of nonviable human sperm can result in normal
      fertilization, it does so at a much reduced rate compared to viable sperm and may
      not result in normally cleaving embryos.

PMID- 9147242
TI  - Human protamines and male infertility.
AB  - PURPOSE: Our purpose was to determine the ratio of protamine 1 to protamine 2 in
      human spermatozoa and relate it to in vitro fertilization rates (IVF) and
      standard semen parameters. METHODS: Couples who had been clinically diagnosed as
      having male-factor infertility and had undergone IVF treatment were grouped
      according to IVF rates and pregnancy outcome. Protamines were extracted and
      separated on acid urea polyacrylamide gels. The P1/P2 ratio correlation with
      semen parameters and IVF rates was investigated using nonparametric analysis.
      RESULTS: The P1/P2 ratio ranged from 0.55 to 1.29 in the control group of
      patients, who had fertilization rates > or = 50% and had achieved a pregnancy in
      one IVF cycle. Of the test patients with IVF < 50%, three (14%) had P1/P2 ratios
      outside the range exhibited by the control group and their sperm possessed large
      heads. CONCLUSIONS: P1/P2 ratios were statistically negatively correlated with
      IVF rates in the control group and with progressive motile sperm concentration in
      the test group. We do not think that altered P1/P2 ratios are the primary cause
      of reduced fertilization.

PMID- 9147243
TI  - An unusual case of rebound ovulation during conservative management of an ectopic
      pregnancy following ovum donation.
AB  - Conservative medical management of ectopic gestations may be difficult in
      patients with elevated levels of beta-hCG and cardiac activity. This case
      highlights the difficulty of managing such patients. Doppler flow studies and
      serum P, if available, should be used and can help determine those patients
      requiring repeated dosing of methotrexate. Patients using donor gametes and
      hormonal supplementation who subsequently develop an ectopic gestation may
      experience "rebound" ovulation, which further clouds the clinical picture.
      Careful follow-up using serial blood testing and ultrasound study is essential in
      the correct interpretation of a potentially confusing clinical picture.

PMID- 9147244
TI  - The pathology and pathogenesis of paratuberculosis in ruminants and other
      species.

PMID- 9147245
TI  - Modulation of host cell activation during feline immunodeficiency virus (FIV)
      infection.
AB  - The authors describe the mitogenic effect of feline immunodeficiency virus (FIV)
      infection (1) in vitro, on feline resting peripheral blood lymphocytes (PBL), and
      (2) in vivo, in experimentally infected cats. Infected PBL were more readily
      recruited than non-infected PBL, into the G1 phase of the cell cycle and showed
      increased expression of the specific cell-cycle markers p53 and p56. In-vivo
      lymphocyte activation following FIV infection was demonstrated by increased
      germinal centre activity in infected lymph nodes, together with a high expression
      of CD30, a B-cell activation marker. These results suggest that early events in
      FIV infection include modulation of host cell activation. Possible implications
      for pathogenesis are discussed.

PMID- 9147246
TI  - Histopathological and immunohistochemical investigation of naturally occurring
      chlamydial conjunctivitis and urogenital inflammation in koalas (Phascolarctos
      cinereus).
AB  - Formalin-fixed conjunctival and urogenital (urinary bladder, urogenital sinus and
      prostate or penis, or both) samples obtained from 29 free-living koalas were
      examined histopathologically and immunohistochemically for the presence and
      character of inflammation and for evidence of chlamydiae. Five koalas had no
      inflammation at any site examined and were chlamydia-negative. Twenty-four koalas
      had inflammation at one or more sites and 18 were positive for chlamydiae by
      serology or antigen detection tests, or both. Histopathological and
      immunohistochemical findings were consistent with those seen in chlamydial
      infections in other species. The inflammatory infiltrate was most dense in the
      lamina propria-submucosa and, in most tissues, predominantly consisted of
      lymphocytes and plasma cells. Neutrophils and macrophages were variable in
      number. Lymphocytes in uninflamed and inflamed tissues consisted largely of T
      cells. B lymphocytes and plasma cells were mainly distributed immediately beneath
      the epithelium, but T cells were widely distributed. MHC H-positive lymphoid
      cells were present in variable numbers and, in some inflamed tissue samples,
      epithelial cell labelling was also seen. Chlamydial inclusion bodies were
      uncommon in routinely stained sections. Immunoperoxidase labelling for chlamydiae
      was positive in 16 of 52 inflamed tissues. The proportion of positive test
      results for chlamydial antigen by any method was directly related to the severity
      of inflammation.

PMID- 9147247
TI  - Abundant expression of viral nucleoprotein mRNA and restricted translation of the
      corresponding viral protein in inclusion body polioencephalitis of canine
      distemper.
AB  - Brain and other tissues of three dogs aged 4-21 months with inclusion body
      polioencephalitis caused by canine distemper virus (CDV) were examined for CDV
      nucleoprotein (N) antigen and mRNA distribution. Two animals (nos 3 and 1) had
      suddenly shown central nervous system (CNS) signs 4 days and 5 months,
      respectively, after vaccination with a modified live CDV vaccine; animal no. 2
      had shown similar signs 4 weeks after vaccination with an unknown product.
      Lesions in the CNS, which were restricted to the grey matter, occurred most
      frequently in the diencephalon, mesencephalon, medulla oblongata and, in one
      animal, in the cerebral cortex. Changes were characterized by mild to moderate
      perivascular lymphohistiocytic cuffs, loss of neurons, neuronal necrosis, glial
      nodules, and oedema. Intranuclear and cytoplasmic inclusion bodies, especially
      prominent in neurons, were observed. By in-situ hybridization, CDV N mRNA
      expression was confirmed with a non-radioactively labelled N-specific mRNA probe.
      The corresponding RNA translation product was detected immunohistochemically with
      a proteinspecific monoclonal antibody. Viral antigen and mRNA were observed in
      the same cell types and brain compartments. However, the number of cells
      expressing N mRNA exceeded the number of cells containing viral antigen greatly
      in two animals and slightly in one. Some areas with abundant viral mRNA
      expression were almost completely devoid of viral antigen. mRNA and the
      corresponding translation product were demonstrated in neurons and less
      frequently in astrocytes, but not in perivascular inflammatory cells. It would
      appear that distemper inclusion-body polioencephalitis may be due to a non
      productive CDV infection of neurons, characterized by abundant expression of CDV
      N mRNA and reduced translation of the corresponding viral protein. These findings
      suggest that in distemper the pathogenesis of grey-matter lesions differs
      substantially from that of white-matter lesions, which constitute the most common
      manifestation of distemper encephalitis.

PMID- 9147248
TI  - Expression of growth factors in chicken growth plate with special reference to
      tibial dyschondroplasia.
AB  - Immunoreactive growth factors were identified in chick embryonic cartilage and
      bone, and in the growth plate of normal tibiotarsi and tibiotarsi affected with
      tibial dyschondroplasia (TD). A specific pattern of temporal and spatial
      expression was observed for each growth factor. Transforming growth factor beta
      and alpha (TGF beta and TGF alpha) and epidermal growth factor (EGF) were briefly
      expressed in chondrocytes of early chick embryos. Immunolabelling for TGF beta
      then gradually shifted into cartilaginous matrix and was not observed in
      cytoplasm of hypertrophic chondrocytes until the late embryonic and post-hatch
      stages. The distribution and intensity of TGF beta labelling was the same in
      chondrocytes of the TD and normal growth plate. Insulin-like growth factor I (IGF
      I) labelling persisted from the early embryonic stage to the end of the mid-stage
      and then disappeared from chondrocytes. IGF-I appeared again in chondrocytes 1-2
      days before hatching. After hatching, the labelling intensified in
      prehypertrophic and hypertrophic chondrocytes. TD lesions displayed IGF-I in the
      distal region, mainly in chondrocytes around small blood vessels. EGF reappeared
      in proliferative and hypertrophic chondrocytes of the mid-embryonic stage. By day
      18 after hatching, EGF was present mainly in prehypertrophic and hypertrophic
      chondrocytes. EGF was demonstrated only in distal proliferative and early
      prehypertrophic chondrocytes of the dyschondroplastic growth plate. TGF alpha was
      identified in hypertrophic chondrocytes adjacent to the periosteum and in the
      distal tip of the mid-embryonic growth plate. With progressing ossification, TGF
      alpha labeling intensified in the embryonic hypertrophic chondrocytes. In the TD
      growth plate at day 18 after hatching, TGF alpha expression was limited to 1-3
      concentric layers of chondrocytes surrounding blood vessels.

PMID- 9147249
TI  - Immunohistochemical demonstration of Wilms tumour gene product WT1 in a canine
      "neuroepithelioma" providing evidence for its classification as an extrarenal
      nephroblastoma.
AB  - An intradural extramedullary tumour, surgically removed from the spinal canal of
      a young dog with paraplegia, had the histological appearance of a nephroblastoma.
      Subsequent necropsy revealed no evidence of a renal primary tumour or of any
      other tumour. Similar tumours of the spinal canal have been described previously
      under a variety of names, in particular neuroepithelioma. With an antibody to the
      human Wilms tumour (nephroblastoma) gene product WT1, labelling of glomeruloid
      bodies, similar to glomerular podocytes in human fetal kidney, was demonstrated
      in the tumour. This finding strengthened the suggestion that it was a
      nephroblastoma.

PMID- 9147250
TI  - A semi-quantitative approach to the selection of appropriate candidate plant
      molluscicides--a South African application.
AB  - The high cost of synthetic molluscicides, used in the control of the intermediate
      snail hosts of schistosomiasis (bilharzia), has resulted in renewed interest in
      plant molluscicides. The history of the use of plant molluscicides is reviewed.
      Although screening programmes have been conducted in other African countries, no
      efforts have been made to identify South African plants which would be suitable
      for use locally, using appropriate technology. The prohibitive costs (time and
      financial) of random surveys for activity necessitated the development of an
      objective selection procedure. A simple scoring system derived for this purpose
      is described. Of 600 plant species with potential, or recorded activity, 150
      occurred in South Africa. Twenty-six taxa were active according to standards set
      by WHO. A further 37 species, although untested, warrant further investigation.
      Species were ranked on cumulative scores for: (a) coincidence of the endemic
      areas of the plant, snail host and disease; (b) ethnomedicinal value which would
      provide greater incentive for cultivation; (c) molluscicidal activity (if known,
      a minimum LD90 of < or = 100 ppm). Two lists resulted, those with recorded and
      those with potential activity. Both are important in prioritizing research on
      molluscicidal plants in South Africa. Problems inherent to the scoring system and
      to the development of plant molluscicides are discussed.

PMID- 9147251
TI  - The molluscicidal activity of Apodytes dimidiata E. Meyer ex Arn (Icacinaceae),
      Gardenia thunbergia L.f. (Rubiaceae) and Warburgia salutaris (Bertol. F.) Chiov.
      (Cannelaceae), three South African plants.
AB  - Mollusciciding is still considered the most important means of control of
      schistosomiasis where the volume of water per caput is small. In rural
      communities the cost of synthetic molluscicides and/or chemotherapy prohibits
      their use. Plant molluscicides, applied as crude aqueous suspensions are the
      source of cheap, effective and environmentally acceptable alternatives. Further,
      infected communities are likely to accept the use of local indigenous plants,
      particularly if they have more than one local application, since they are
      familiar with their properties and growth characteristics. In this study the
      activity of crude aqueous suspensions of six South African plants were assessed.
      Suspensions of leaf material were bioassayed for activity using Bulinus
      africanus. Probit analysis was used to calculate LD50 and LD90 values. Three
      species would receive priority for further investigations of extract stability
      and toxicology, i.e. comprehensive evaluation. For this purpose species were
      ranked on toxicity as aqueous suspensions, the highest toxicity level previously
      recorded in the literature, and on their cultivation potential. Ranks for each
      plant were summed and Gardenia thunbergia, Apodytes dimidiata, and Warburgia
      salutaris had the lowest cumulative rankings (i.e. the highest molluscicidal
      activity and greatest cultivation potential).

PMID- 9147252
TI  - Effects of Ampelopsis brevipedunculata (Vitaceae) extract on hepatic M cell
      culture: function in collagen biosynthesis.
AB  - A spirits-extracted fraction of berries of Ampelopsis brevipedunculata (Maxim.)
      Trautv. (Vitaceae) is used in Japanese folk medicine to treat liver disease.
      Since such an extract has been shown to inhibit formation of collagen fibers by
      rat hepatic M cells, it was felt that the extract acts as an inhibitor of hepatic
      fibrosis. Amino acid analysis of fibrous substances developing on M cell layers
      and of a cell lysate fraction indicated that an A. brevipedunculata extract
      inhibited collagen formation. Biosynthesis of non-collagenous proteins and
      collagen was evaluated by measuring the extent of [3H]tryptophan incorporation
      into a protein fraction and the rate of [3H]proline incorporation into a
      collagenase-digestible fraction, respectively. In contrast to the results of the
      analysis of the fibrous substances, the A. brevipedunculata extract failed to
      decrease synthesis of non-collagenous proteins and collagen unless cell
      proliferation was inhibited. There was no detectable level of collagenolytic
      activity in the M cell culture with the A. brevipedunculata extract. The decrease
      in accumulation of collagen, therefore, appeared to be a consequence of the
      proliferation-inhibitory effect of the A. brevipedunculata extract. Such
      inhibitory activity was found in a macromolecular fraction that contained
      abundant sugars but lacked proteins.

PMID- 9147253
TI  - Gastrodin and p-hydroxybenzyl alcohol facilitate memory consolidation and
      retrieval, but not acquisition, on the passive avoidance task in rats.
AB  - Gastrodin (GAS) and p-hydroxybenzyl alcohol (HBA) which is an aglycone of
      gastrodin, are active ingredients of Gastrodia elata Blume. In this study, we
      attempted to investigate the effects of acute administration of GAS and HBA on
      learning and memory processes such as acquisition, consolidation and retrieval,
      on the passive avoidance task in rats; piracetam was used as a positive control.
      Scopolamine, impairing learning acquisition, shortened the step-through latency
      in the retention test in rats. GAS and HBA did not prolong the step-through
      latency induced by scopolamine in the passive avoidance task, but piracetam could
      prolong the step-through latency induced by scopolamine. Cycloheximide, impairing
      memory consolidation, shortened the step-through latency in the retention test in
      rats. GAS at 50 mg/kg, HBA at 5 mg/kg and piracetam at 100 mg/kg could prolong
      the step-through latency induced by cycloheximide in the passive avoidance task.
      Apomorphine, impairing memory retrieval, shortened the step-through latency in
      the retention test in rats. GAS at 5 mg/kg, HBA at 1 mg/kg and piracetam at 300
      mg/kg could prolong the step-through latency induced by apomorphine in the
      passive avoidance task. From the above results, we concluded that the
      facilitating effects of HBA on learning and memory are better than those of GAS.
      In conclusion, GAS and HBA can improve cycloheximide- and apomorphine-induced
      amnesia, but not scopolamine-induced acquisition impairment in rats. Thus, GAS
      and HBA can facilitate memory consolidation and retrieval, but not acquisition.
      The facilitating effects of GAS and HBA are different from those of piracetam.

PMID- 9147255
TI  - Hepatoprotective activity of Boerhaavia diffusa L. roots--a popular Indian
      ethnomedicine.
AB  - The roots of Boerhaavia diffusa L., commonly known as 'Punarnava', are used by a
      large number of tribes in India for the treatment of various hepatic disorders.
      In the present study the effect of seasons, thickness of roots and form of dose
      (either aqueous or powder) were studied for their hepatoprotective action to
      prove the claims made by the different tribes of India. The hepatoprotective
      activity of roots of different diameters collected in three seasons, rainy,
      summer and winter, was examined in thioacetamide intoxicated rats. The results
      showed that an aqueous extract (2 ml/kg) of roots of diameter 1-3 cm, collected
      in the month of May (Summer), exhibited marked protection of a majority of serum
      parameters, i.e. GOT, GPT, ACP and ALP, but not GLDH and bilirubin, thereby
      suggesting the proper size and time of collection of B. diffusa L. roots for the
      most desirable results. Further, the studies also proved that the aqueous form of
      drug (2 ml/kg) administration has more hepatoprotective activity than the powder
      form; this is probably due to the better absorbtion of the liquid form through
      the intestinal tract.

PMID- 9147254
TI  - Antiandrogenic effect of Striga orobanchioides.
AB  - The ethanolic extract of the whole plant of Striga orobanchioides given for 7
      days to immature male rats at a dose level of 200 mg/kg body weight caused a
      significant decrease in the weight of the testes, epididymis, seminal vesicles
      and the ventral prostate. It also produced degenerative changes of Leydig cells,
      their nucleus, the seminiferous tubules and a significant decrease in the number
      of spermatocytes and spermatids. The seminiferous tubules of the treated rats are
      shrunken and compactly arranged. The antiandrogenic or antispermatogenic effect
      of the extract is discussed.

PMID- 9147256
TI  - Ampelopsis brevipedunculata (Vitaceae) extract stimulates collagen synthesis
      through superoxide generation in the serum-free cultures of rat dermal
      fibroblasts and Ito cells.
AB  - We describe the effects of an ethanol-extracted fraction of berries of Ampelopsis
      brevipedunculata (Maxim.) Trautv. (Vitaceae), a plant used in folk medicine to
      treat liver disease, on the synthesis of non-collagenous proteins and collagen by
      rat collagen-producible cells such as dermal fibroblasts and liver non
      parenchymal Ito cells. The generation of superoxide and hydroxyl radical was
      assessed by measuring the reduction of cytochrome c and the formation of
      thiobarbituric acid-reactive substances from deoxyribose, respectively. The
      synthesis of non-collagenous proteins and collagen as evaluated by measuring the
      extent of [3H]tryptophan incorporation into a total protein fraction of culture
      products and the [3H]proline-incorporating rate into a collagenase-digestible
      protein fraction, respectively. Both types of cells promptly synthesized only
      collagen in response to a dialyzable fraction of the extract. Major activity to
      generate oxygen free radicals accumulated in the dialyzable fraction whereas
      activity to decrease ferrous iron-mediated generation of the radicals accumulated
      in an undialyzable fraction of the extract. Stimulation of collagen synthesis was
      caused by superoxide because addition of superoxide dismutase but not pyruvate,
      an antioxidant of hydrogen peroxide, or dimethyl sulfoxide, an antioxidant of the
      hydroxyl radical, abrogated the stimulatory effect. The extract may arrest the
      progress of liver injury mediated by oxygen free radicals generated in the
      presence of ferrous iron.

PMID- 9147257
TI  - Studies on antitussive activity of Drymaria cordata Willd. (Caryophyllaceae).
AB  - The methanol extract of Drymaria cordata Willd. was investigated for its effect
      on a cough model induced by sulfur dioxide gas in mice. It exhibited significant
      antitussive activity when compared with the control in a dose-dependent manner.
      The antitussive activity of the extract was comparable to that of codeine
      phosphate, a prototype antitussive agent. The D. cordata extract (100, 200, 400
      mg/kg) showed 11.6%, 31.6% and 51.5% inhibition of cough with respect to the
      control group.

PMID- 9147258
TI  - Antibacterial activity of South African plants used for medicinal purposes.
AB  - Crude extracts from 21 South African medicinal plants, traditionally used for
      ailments of an infectious or septic nature, were screened for in vitro
      antibacterial activity using the agar diffusion and dilution methods. Almost all
      the activity exhibited was against Gram-positive bacteria, with 12 of the 21
      plant species tested showing some activity against Bacillus subtilis. Only the
      Warburgia salutaris methanol extract inhibited the growth of Escherichia coli.
      None of the extracts had any activity against Klebsiella pneumoniae. The highest
      activity was found in the methanol extracts from Bidens pilosa, Psidium guajava,
      Artemisia afra and Warburgia salutaris. The majority of the antibacterial
      activity was present in the methanolic, rather than the aqueous extracts.

PMID- 9147259
TI  - Inhibitory effects of ethanolic extracts of Boussingaultia gracilis on the
      spasmogen-induced contractions of the rat isolated gastric fundus.

PMID- 9147260
TI  - Activism and marginalization in the AIDS crisis.

PMID- 9147261
TI  - Gatekeeping through media format: strategies of voice for the HIV-positive via
      human interest news formats and organizations.
AB  - This research examines the extent to which HIV-positive voices are marginalized
      in the mainstream versus the "alternative" press. The central claim of this
      research is that news media format considerations, constructed around what has
      come to be called "media logic," leave persons who are HIV-positive with
      comparatively little voice in the mainstream press. By utilizing techniques of
      content analysis, the research examines 535 major HIV/AIDS-specific stories
      published in two oppositional papers toward an assessment of the level of HIV
      positive voice in each outlet. While arguments of "homophobia" have been
      previously used to explain bias in mainstream HIV/AIDS-coverage, this article
      asserts that "heterocentric" bias is, in fact, embedded in the routinized
      practices of mainstream "news production." The article concludes by suggesting
      that successful future HIV/AIDS-activism demands a recognition of "media logic"
      and an adoption of its tactics.

PMID- 9147262
TI  - Truth and deception in AIDS information brochures.
AB  - This essay documents state governmental subversion of expansive constructions of
      HIV-disease. While it is clear that governments frequently practice deception and
      secrecy with the justification that the public would become dangerously emotional
      and irrational if fully informed, there is no evidence that the public would, in
      fact, behave that way. The essay concludes with a ranking of state AIDS brochures
      for accuracy and totality of information.

PMID- 9147263
TI  - The social construction of target populations and the transformation of prison
      based AIDS policy: a descriptive case study.
AB  - When interpreting policy changes, it is important to understand the social
      construction of those whom the policy affects. Policy Design Perspective by
      Schneider and Ingram (1993) concentrates on the construction of "agents" and
      "targets" in an attempt to comprehend policy formation and transformation. The
      following descriptive case study uses this design to assess the evolution of one
      prison's AIDS policy. This institution's HIV/AIDS policy originally was quite
      restrictive in nature, but the changing perceptions of the agents and targets
      allowed a more humanistic approach to emerge in the handling of HIV-positive
      inmates.

PMID- 9147264
TI  - The problem with making AIDS comfortable: federal policy making and the rhetoric
      of innocence.
AB  - This essay presents a narrative of U.S. AIDS policy which highlights the ways
      that people with AIDS (PWAs) have been categorized throughout the epidemic. I
      argue that PWAs have been broadly categorized as either "innocent" or "guilty" in
      the public discourse about AIDS, and that these distinctions have greatly
      influenced the way that policies are designed and justified. An examination of
      the Ryan White CARE Act of 1990 shows that policy rationales of lawmakers
      overwhelmingly relied on rhetoric which focused on the most sympathetic PWAs:
      "innocent" women and children. While this rhetorical strategy helped gain passage
      of the law, it effectively shut out the concerns of the majority of PWAs who fell
      into less sympathetic categories and resulted in policy decisions which often
      work against the stated goals of lawmakers.

PMID- 9147265
TI  - A citizens' AIDS Task Force: overcoming obstacles.
AB  - This article analyzes the experience of a state-wide Task Force on AIDS using
      grassroots techniques to construct policy responsive to the needs of people
      living with HIV. The four primary obstacles to effective policy making were the
      need (1) to include disenfranchised groups; (2) to avoid the domination of
      governmental bureaucracy so that community-based organizations could offer
      solutions, as well as services; (3) to overcome resistance to anonymous testing;
      and (4) to reach "hard to reach" populations. Task Force members' perspectives
      colored what were deemed appropriate policies. Members tended to polarize into
      two groups: those community-based groups and individuals who focused on the needs
      of people with HIV on one side, and on the other side, more institutional players
      who wanted to identify and isolate "HIV carriers." The article closes by
      analyzing the resulting HIV Omnibus Bill. Those who focused on the needs of
      people with HIV seized the opportunity to draft and successfully pass an omnibus
      bill through the Arizona Legislature. This success demonstrates that highly
      organized communities can affect policy making, even to the extent that it
      offsets more institutionalized power.

PMID- 9147266
TI  - AIDS and the new medical gaze: bio-politics, AIDS, and homosexuality.
AB  - The essay argues that the contemporary resurgence of homophobia and the
      remedicalization of homosexuals in the wake of AIDS is, in part, an unintended
      but predictable effect of a quarter century of fractious identity-politics.
      Prominent gay and lesbian political strategies of the 1970s and 1980s borrowed
      heavily from increasingly discredited, if once politically correct, discourses
      that valorized individuals on the basis of membership in governmentally
      constructed bio-bureaucratic categories. Drawing on the work of prominent gay
      intellectuals, such as Foucault, Watney, and Richard Rodriguez, and locating
      their insights within the context of contemporary cultural and political
      conflicts, the essay argues that gay advocates who essentialize homosexual
      identity, however benignly, unwittingly participate in constituting the ground
      for an emergence of a neoeugenic movement at millennium's end. The essay
      concludes with the observation that escaping the conceptual prison of bio
      bureaucratic categories is not a uniquely gay or lesbian task. It is a human
      task.

PMID- 9147267
TI  - Lipopeptide inhibitors of fungal glucan synthase.
AB  - The echinocandins and pneumocandins are lipopeptide antifungal agents that
      inhibit the synthesis of 1,3-beta-D-glucan, an essential cell wall
      homopolysaccharide found in many pathogenic fungi. Compounds with this fungal
      specific target have several attractive features: lack of mechanism-based
      toxicity, potential for fungicidal activity and activity against strains with
      intrinsic or acquired resistance mechanisms for existing antimycotics. Semi
      synthetic analogues of naturally occurring lipopeptides are currently in clinical
      trials with the aim of treating systemic candidiasis and aspergillosis. Thus a
      fuller understanding of the target enzyme and its inhibition by these compounds
      should be useful for epidemiological and other clinical studies. Although it has
      been long known that lipopeptides inhibit fungal glucan synthase activity both in
      cell extracts and in whole cells, the genetic and biochemical identification of
      the proteins involved has been accomplished only recently. We now know that in
      Saccharomyces cerevisiae, glucan synthase is a heteromeric enzyme complex
      comprising one large integral membrane protein (specified by either FKS1 or by
      FKS2) and one small subunit more loosely associated with the membrane (specified
      by RHO1). Additional components may also be involved. The heteromeric enzyme
      complex containing Fks1p constitutes the majority of the activity found in
      vegetatively growing cells in this organism. The FKS2 gene product is needed for
      sporulation. Lipopeptides affect the function of the Fksp component from either
      FKS gene. The current model for interaction and regulation of these components in
      S. cerevisiae and the application to Candida albicans and other pathogenic fungi
      are discussed in this review.

PMID- 9147268
TI  - Molecular bases of adhesion of Candida albicans.
AB  - The purpose of this review is to focus on the location and the adhesion activity
      of the protein (peptide) and the mannan moieties of the mannoprotein in the outer
      surface of the Candida albicans cell wall. A macromolecule of the mannoprotein
      located on the outermost surface is undoubtedly a strong adhesin comprising
      several adhesion molecules including protein and mannan. Mannoproteins can be
      divided into two classes, higher molecular weight peptidomannans (260 kDa) and
      lower molecular weight mannoproteins (50-66 kDa), both of which consist of
      similar mannans and disparate proteins or peptides which have distinct adhesion
      specificities. The protein moiety of mannoprotein can be divided functionally
      into two groups, lectin-like proteins and proteins recognizing arginine-glycine
      aspartic acid (RGD) ligands. The latter proteins are further subdivided into two
      groups, CR2/CR3-like proteins and proteins binding extracellular matrix (ECM)
      proteins. Hydrophobicity of the cell surface of C. albicans influences adhesion
      of the organisms to epithelial cells. Degree of glycosylation of cell surface
      mannoproteins that affect yeast cell surface hydrophobicity affects adhesion of
      C. albicans to epithelial cells. The hydrophobic proteins may have low levels of
      glycosylation, and changes in glycosylation may determine exposure of hydrophobic
      protein regions at the cell surface. The serotype A-specific oligosaccharide of
      antigen 6 (pentaose or hexaose of mannan moiety) has been shown to exhibit marked
      adhesion ability for epithelial cells, and mannotetraose related to antigenic
      factor 5 which is present in both serotypes A and B showed adhesive activity for
      tissue macrophages. Proteinoceous adhesins of C. albicans are expressed
      preferably on the mycelial form. It is suggested that several of the adhesion
      molecules of C. albicans described above appear to complementarily utilize
      multiple adhesion mechanisms.

PMID- 9147269
TI  - Blood supply and vasculature of mycetoma.
AB  - The blood supply to the mycetoma lesion and its vasculature were studied in
      patients with various types of mycetoma using histological, ultrastructural,
      angiographic and sonographic techniques. The mycetoma lesion proved to be well
      vascularized. However, certain vascular abnormalities were demonstrated. In
      histological sections, the small arteries and arterioles showed medial muscular
      hypertrophy in 83%, intimal fibrosis in 33%, arteritis in 7% and endarteritis
      obliterans with narrowed lumen in 7% of the patients. No vascular occlusion,
      ischaemic changes or arteriovenous shunts were observed. These changes were
      confirmed ultrastructurally. Angiography of the lesion showed a brisk
      pathological circulation which was more evident in eumycetoma. The vascular
      Doppler study showed normal blood flow pattern in the affected limb. Regional
      intra-arterial chemotherapy for mycetoma is suggested as a possible treatment
      modality.

PMID- 9147270
TI  - Invasive Fusarium infections: a retrospective survey of 31 cases. The French
      'Groupe d'Etudes des Mycoses Opportunistes' GEMO.
AB  - A retrospective study was conducted in France to investigate Fusarium infections
      which are now recognized as emerging opportunistic infections. The clinical and
      mycological findings for 31 cases diagnosed between 1984 and 1993 by members of
      the French Groupe d'Etudes des Mycoses Opportunistes were analysed. All suffered
      from haematological disease, most often acute leucaemia (n = 19). Twenty-two had
      received cytostatic chemotherapy and ten had undergone bone marrow
      transplantation. Prolonged aplasia and pancytopenia were present in 18 and 11
      patients, respectively. Skin (61%) and blood (42%) were the sites most frequently
      involved. Fusarium solani (n = 7), Fusarium oxysporum (n = 7), Fusarium
      verticilloides (n = 7) were the species most frequently isolated. Nine antifungal
      treatments were used, associated with colony-stimulating factors in five cases.
      None was unambiguously superior to all the others. The overall mortality was
      51.6% with a specific mortality > or = 25.8%. The disseminated form of the
      infection was associated with poor prognosis (P < 0.02) whereas improving
      granulocyte count improved prognosis (P < 0.001). More aggressive cytostatic
      regimens used for patients with haematological malignancies have favoured the
      emergence of Fusarium infections. As prognosis is closely correlated with
      neutrophil recovery, the promising results obtained with the use of colony
      stimulating factors should be further evaluated.

PMID- 9147271
TI  - Atypical strains of Candida albicans recovered from AIDS patients.
AB  - By using multilocus enzyme electrophoresis (MLEE) we have analyzed the genetic
      diversity encountered among chlamydospore-positive Candida albicans strains.
      While the type II strains of the former C. stellatoidea were genetically
      indistinguishable from those of C. albicans, type I strains constituted a
      distinct subgroup compared with C. albicans strains. Nevertheless, all these
      strains remained genetically very closely related compared with other species of
      Candida (e.g. C. tropicalis, C. krusei and C. glabrata). These results
      corroborate the synonymy between C. stellatoidea and C. albicans. Chlamydospore
      positive C. albicans strains with atypical sugar assimilation patterns displayed
      a great genetic divergence from the cluster constituted by C. albicans and the
      strains of the former C. stellatoidea. However, these atypical strains were more
      closely related to C. albicans than they were to C. tropicalis, C. krusei or C.
      glabrata. These strains represent a genetically entity distinct from the typical
      C. albicans strains used in this study. The data also support the view that the
      atypical strains described here belong to the same genetic group as atypical C.
      albicans strains previously described by others.

PMID- 9147272
TI  - Western immunoblot analysis of protein antigens of Penicillium marneffei.
AB  - Protein antigens of Penicillium marneffei prepared during the yeast and mould
      phases of in vitro growth were analyzed by gel electrophoresis and immunoblot
      assay. More than 20 yeast phase proteins were detected by Coomassie staining;
      among these, at least 10 reacted with IgG in the pooled sera of 28 AIDS patients
      with penicilliosis. Four immunogenic proteins of 200, 88, 54 and 50 kDa were
      produced in large quantity during the deceleration and early stationary phases of
      growth. When these proteins were reacted with individual sera derived from 33
      AIDS patients with penicilliosis, reactivities to the 200, 88, 54 and 50 kDa
      protein were detected in 72.7, 93.9, 60.6 and 57.6%, respectively. The bands of
      88, 54 and 50 kDa gave strong reactions with about a half of serum samples. In
      one serum derived from an AIDS patient, reactivities to the 54 and 50 kDa
      proteins could be strongly detected two months before the definite diagnosis by
      fungal culture. Protein components from the mould form were of lower yield and
      gave weaker signal in immunoblot analysis. These results indicate that at least
      two yeast-phase immunoreactive proteins (54 and 50 kDa) are relatively specific
      to the P. marneffei infection, thereby suggesting its potential for clinical
      application to the diagnosis of this emerging disease.

PMID- 9147273
TI  - New evidence that Candida albicans possesses additional ATP-binding cassette MDR
      like genes: implications for antifungal azole resistance.
AB  - Emergence of resistance of Candida albicans to antifungal triazoles is
      increasingly recognized as an important cause of refractory mucosal candidiasis
      in HIV-infected patients. Recently, CDR1, which is thought to be analogous to the
      human MDR-1 P-glycoprotein, has been cloned in C. albicans. It has been proposed
      that its expression is partially responsible for fluconazole resistance in C.
      albicans. This gene is characterized by the presence of an ATP binding cassette
      (ABC) region and is distinct from the BENr gene which does not encode such a
      functional domain. As the molecular basis for fluconazole resistance appears to
      be multifactorial, we considered that there may be other ATP binding cassette
      containing MDR genes that may potentially contribute to antifungal azole
      resistance in C. albicans. We therefore sought to identify potential target
      sequences that may be derived from candidate genes that share homology with the
      ATP binding cassette region of the human MDR-1 P-glycoprotein. Degenerate
      oligonucleotide primers based on the known sequence from the ATP binding cassette
      region of the human MDR-1 P-glycoprotein were used to amplify PCR products within
      the range of 100 bp in length from C. albicans isolates (3 fluconazole
      susceptible and 3 fluconazole-resistant). Sequence analysis of individually
      subcloned PCR products, derived from the six isolates revealed 34 sequences in
      total. The results of our study identified 14 clones (with at least one per
      isolate) with a high degree of homology to the ATP binding cassette of the human
      MDR-1 P-glycoprotein. The BLAST search did not disclose homology of these new
      sequences to the C. albicans CDR1 gene, suggesting that C. albicans may possess
      more than one MDR-like gene. We conclude that C. albicans may possess one or more
      additional genes encoding ATP binding cassette MDR-like proteins that are
      distinct from CDR 1 and which could participate in the development of fluconazole
      resistance.

PMID- 9147274
TI  - A case of prosthetic valve endocarditis caused by Cryptococcus neoformans var.
      neoformans.
AB  - A case of prosthetic valve endocarditis caused by Cryptococcus neoformans var.
      neoformans is described. The infection followed closed mitral valvotomy and
      insertion of a valvular prosthesis. Infection was manifested 2 weeks after the
      operation. The diagnosis was based on direct demonstration of the yeast with
      characteristic morphology in clinical material, isolation from an arterial
      thrombus and detection of cryptococcal antigen in the serum. The patient's
      infection could not be resolved despite institution of antifungal therapy.

PMID- 9147275
TI  - Prevalence of phthioic acid in Aspergillus species.
AB  - We examined fast atom bombardment mass spectra (FAB-MS) of 29 clinical isolates
      of Aspergillus, from five pathogenic species, for the presence of phthioic acid
      anions (m/z 395.6) when grown at 37 degrees C. Phthioic acid was detected in only
      one of 12 A. fumigatus, three of nine A. terreus and one of four A. niger
      isolates. Phthioic acid is unlikely to be a major pathogenicity determinant of
      Aspergillus.

PMID- 9147276
TI  - Differential killer toxin sensitivity patterns of varieties of Cryptococcus
      neoformans.
AB  - Ten different killer sensitivity types are distinguished within Cryptococcus
      neoformans, namely four in var. neoformans and six in var. gattii. All strains of
      the var. gattii investigated were inhibited by killer toxins of C. laurentii CBS
      139, whereas those of the var. neoformans were not. Killer sensitivity patterns
      are an easy-to-use method to differentiate between the two varieties of the
      clinically important yeast C. neoformans, and may be of help in epidemiological
      surveys.

PMID- 9147277
TI  - Comments on Cladophialophora bantiana.

PMID- 9147278
TI  - The effect of ethylcellulose molecular weight on the properties of theophylline
      microspheres.
AB  - Microspheres of theophylline, with both ethylcellulose of high and low molecular
      weight and also their mixtures as a coating material, were prepared using the
      solvent evaporation technique. No permeability through intact isolated polymer
      films was found. Therefore, this study investigated the drug release dependence
      of structure and mechanical properties of the polymer matrix. In vitro
      dissolution studies exhibited the square-root of time (Higuchi model) release
      characteristics. The size distribution of microspheres was dependent on the ratio
      of ethylcellulose mixtures with high and low molecular weights.

PMID- 9147279
TI  - The influence of microencapsulation using Eudragit RS100 on the hydrolysis
      kinetics of acetylsalicylic acid.
AB  - Homogeneous Eudragit RS100 matrix microspheres containing molecularly dispersed
      acetylsalicylic acid (ASA) were prepared in order to investigate the effect of
      encapsulation on the decomposition rate of a hydrolytically susceptible drug. ASA
      loaded microspheres of this non-eroding polymer matrix were analysed at
      predetermined time points following immersion of the microspheres in temperature
      controlled buffer systems at pH 1.2 or pH 12.1 at 30, 40 or 50 degrees C. The
      mass balance of the total amount of solutes (ASA and SA) initially located within
      the microsphere interior was equal to the sum of the amount of solutes remaining
      in the microsphere interior and the amount of solutes in the aqueous phase at any
      time during the course of the study. Each analysis involved the quantitation of
      four species; the drug and decomposition product, salicylic acid (SA), in both
      the microspheres phase and the external aqueous phase. A simple model system
      using first-order rate approximations for the concurrent Fickian diffusion and
      hydrolysis decomposition of the drug resulted in a multiexponential expression
      which adequately described the time-course profile of the drug. SA-loaded
      microspheres were used as a control under similar conditions to determine the
      magnitude of the contribution of microsphere phase hydrolysis of ASA to the
      overall rate of drug loss from the microspheres. Results indicated that
      microspheres phase hydrolysis of ASA was minimal. Even after 900 h of immersion
      in pH 12.1 buffer some ASA remained within the microsphere. It is postulated that
      the matrix incorporated drug is essentially shielded from hydrolytic attack until
      it is liberated into the external aqueous environment. Electrostatic association
      of the drug with the charged quaternary residues in the polymer along with the
      limiting availability of water within the microsphere may be responsible for the
      observed stability of ASA in aqueous swollen ASA-loaded Eudragit microspheres.

PMID- 9147280
TI  - Thymopentin loaded microsphere preparation by w/o/w emulsion technique: in
      vitro/ex vivo evaluation.
AB  - Poly-D,L-lactide (PDLLA) and polylactide-co-glycolide (PLGA) microspheres
      containing thymopentin have been prepared by a water-in-oil-in-water
      emulsion/solvent evaporation technique. The goal is to stabilize the active
      compound thymopentin, and to prolong its therapeutic activity, by embedding the
      drug in a polymeric matrix. The microspheres obtained have been characterized for
      their morphology and drug content. In-vitro dissolution tests have been performed
      on the microspheres. Results show that the type of polymer employed (PDLLA or
      PLGA) does not seem to affect microsphere morphology, while in-vitro dissolution
      profiles are greatly influenced by the composition of polymer matrix. Ex-vivo
      evaluation of PLGA microspheres performed on mouse thymocites shows that
      biological activity of Thymopentin is maintained after loading into PLGA
      microspheres.

PMID- 9147281
TI  - Insulin in w/o/w multiple emulsions: preparation characterization and
      determination of stability towards proteases in vitro.
AB  - In this work two w/o/w multiple emulsions composed of soybean oil or medium-chain
      triglycerides and containing insulin were studied. These emulsions were prepared
      by means of two-step emulsification procedure. The w/o/w emulsions obtained were
      stable for at least 6 months of storage at 4-6 degrees C. The yield of
      encapsulation of insulin was > 95%. The main release mechanism is a swelling
      breakdown phenomenon. In vitro, the two w/o/w multiple emulsions were able to
      protect insulin against enzymatic degradation. These results indicate that
      multiple emulsions have potential as a carrier of insulin for oral
      administration.

PMID- 9147282
TI  - Insulin in w/o/w multiple emulsions: biological activity after oral
      administration in normal and diabetic rats.
AB  - In this work the biological effects of two w/o/w multiple emulsions composed of
      the soybean oil (EHS) or medium-chain triglycerides (ETCM), containing insulin,
      were studied. The release mechanism of insulin from multiple emulsions proposed
      in our previous in-vitro investigations was confirmed by subcutaneous
      administration. This mechanism is the swelling-breakdown phenomenon which occurs
      when the emulsions are diluted under hypo-osmotic condition. The biological
      effect after oral administration, evaluated in two experimental protocols, single
      administration in normal and diabetic rats and short-term treatment in diabetic
      rats, shows that in diabetic rats small amounts of biologically active insulin
      were absorbed from these emulsions. In these experiments no significant
      difference between EHS and ETCM was found.

PMID- 9147283
TI  - In vitro kinetics of drug release and pulmonary retention of microencapsulated
      antibiotic in liposomal formulations in relation to the lipid composition.
AB  - In previous in-vivo studies, we demonstrated that liposomal entrapment of
      tobramycin resulted in an increased availability of the antibiotic in the lungs
      without increasing bactericidal efficacy (Omri et al. 1994). With the aim of
      developing liposomal formulations allowing more efficient liposome-bacteria
      interactions, we studied the influence of lipid composition on both drug release
      and pulmonary retention of encapsulated tobramycin. The phase transition
      temperatures of nine liposome-tobramycin formulations consisting of two synthetic
      phospholipids (distearoyl phosphatidylcholine (DPSC) or dipalmitoyl
      phosphatidylcholine (DPPC) with dimyristoyl phosphatidyl-glycerol (DPMG) or
      dimyristoyl phosphatidylcholine (DMPC) were determined by differential scanning
      calorimetry. Liposomes, varying in terms of membrane fluidity and charge were
      submitted to in-vitro and in-vivo kinetic studies while retention and release of
      tobramycin were measured by high-performance liquid chromatography (HPLC). Five
      less fluid liposome formulations showed absence or very low tobramycin release in
      in-vitro tests and long term pulmonary retention of tobramycin. Four fluid
      liposome formulations showed in vitro tests modulated tobramycin release while
      pulmonary retention of tobramycin was dependent of the presence of charged
      phospholipids. Administration of charged fluid liposomes in mice showed a low
      level of tobramycin in the kidneys; non-charged fluid liposomes exhibited a
      relatively high level of tobramycin retention in the kidneys.

PMID- 9147284
TI  - Influence of formulation variables on the in-vitro release of albumin from
      biodegradable microparticulate systems.
AB  - Poly(D,L-lactide-co-glycolide) microspheres containing BSA were prepared by a
      modified solvent evaporation method using a double emulsion. These microspheres
      were characterized for size, morphology, surface absorbed protein, encapsulation
      efficiency and release kinetics. The influence of two formulation variables (the
      procedure to obtain the first emulsions and the lyophilization of the
      microspheres once obtained) on the physical characteristics and release behaviour
      of the microspheres was also investigated. Sonicated microspheres were smooth and
      spherical, with a mean particle size of 20 microns and an encapsulation
      efficiency of 81%. When the first emulsion was prepared by vortex mixing the
      particles were irregular and porous, with a mean size of 31 microns and a lower
      encapsulation efficiency (56%). The sonication allows a more homogeneous emulsion
      as well as a lower percentage of albumin adsorbed on the surface. The in vitro
      release profile was described as a biexponential process with an initial burst
      effect due to the release of the protein adsorbed on the microsphere surface and
      a second sustained release phase due to protein diffusion through the channels or
      pores formed in the polymer coat. The release of BSA was dependent on the
      preparation method. The greatest burst release was found for microspheres
      formulated using the vortex mixer, 58% of the encapsulated protein was released
      during the first 24 h, whereas sonicated microspheres released 32.2%. This burst
      effect could be reduced by lyophilizing the microspheres following their
      preparation. The amount of protein released decreased to 28.3% and 51.6% in
      sonicated and non-sonicated microspheres respectively, when they were
      lyophilized.

PMID- 9147286
TI  - Sustained-release microcapsules of nitrofurantoin and amoxicillin; preparation,
      in-vitro release rate, kinetic and micromeritic studies.
AB  - In this work, nitrofurantoin and amoxicillin trihydrate microcapsules were
      prepared by complex coacervation at pH 3.5 using carboxymethylcellulose-gelatin
      at a weight ratio of 3:7. Release rates were studied as a function of core:wall
      ratios of microcapsules. Dissolution tests of microcapsules and their tabletted
      microcapsules were studied in artificial gastric and intestinal media without
      enzyme using the USP XXII basket method. Release rates were examined kinetically
      and the ideal kinetic models were estimated for drug release. In addition, the
      micromeritics of these microcapsules were investigated. In order to standardize
      the drug powder and the microcapsule product for industrial application, the
      micromeritic properties of microcapsules were studied by determining their bulk
      volume and weight, tapping volume and weight, fluidity, angle of repose, weight
      deviation, particle size distribution, density and porosity. Hausner ratio and
      consolidation index were also calculated to understand flowability rates of
      microcapsules when tableting or filling into gelatin capsules. The results
      indicated that the nitrofurantoin microcapsules need appropriate glidant but the
      amoxicillin trihydrate microcapsules did not. Moreover, it was observed that the
      microencapsulation changed the micromeritic properties of the drugs
      significantly.

PMID- 9147285
TI  - Chemical, dissolution stability and microscopic evaluation of suspensions of
      ibuprofen and sustained release ibuprofen-wax microspheres.
AB  - Chemical stability studies of suspensions of ibuprofen powder and ibuprofen-wax
      microspheres were performed using an accelerated stability protocol with a
      modified high performance liquid chromatography (HPLC) procedure. The variables
      considered were pH, suspending agents and temperature. The study showed little or
      no chemical degradation in the different suspending agents after storage for
      three months. Dissolution stability was examined in suspensions of ibuprofen
      microspheres made from an optimized formulation with 17% drug loading. The
      storage temperature were 23, 37 and 45 degrees C. Other variables for the
      dissolution stability studies were suspending agents, wax types, suspending
      medium pH and microsphere size. Suspensions of ceresine wax microspheres stored
      at 37 degrees C showed faster drug release than room temperature storage, but
      suspensions stored at 45 degrees C showed an opposite effect. Microspheres
      suspended in syrup and stored at 37 degrees C had faster dissolution rates than
      microspheres suspended in methylcellulose at the same temperature, possibly as a
      result of an interaction between the syrup and the microsphere constituents.
      Suspensions of microcrystalline wax microspheres had better dissolution stability
      than microspheres made from ceresine wax. Higher suspending medium pH resulted in
      faster release of drug from the suspended microspheres, but particle size did not
      significantly affect the dissolution stability.

PMID- 9147287
TI  - Changes in distribution of cystatin C, apolipoprotein E and ferritin in rat
      hypothalamus after hypophysectomy.
AB  - To clarify the mechanism underlying the process of degeneration of injured CNS
      neurons, we have immunohistochemically examined the distribution of cystatin C,
      apolipoprotein E, IgG, transferrin and ferritin in the hypophysectomized rat
      hypothalamus. Stainings for ferritin revealed that reactive microglial cells
      massed in the paraventricular and supraoptic nuclei 14 days after hypophysectomy,
      when the degeneration of vasopressin neuronal cell bodies was apparent. Cystatin
      C-positive magnocellular neurons first appeared at 4 days and the number of
      intensely-stained cells increased rapidly up to the 7th day of hypophysectomy,
      followed by a decrease thereafter. Most of such cystatin C-positive neurons were
      simultaneously stained with anti-vasopressin serum. Accumulation of
      apolipoprotein E in extracellular spaces was obvious in the both hypothalamic
      magnocellular nuclei at 7 days. Several apolipoprotein E-positive cells were
      localized in the supraoptic nucleus, although the number of apolipoprotein E
      positive cells was much smaller than that of cystatin C-positive cells. The
      experiments performed with the transferrin and IgG antibodies showed undetectable
      levels of such molecules in and around the degenerating magnocellular neurons
      during whole experimental periods. These findings suggest the importance of
      cystatin C and apolipoprotein E in the process of degeneration and/or
      regeneration of magnocellular neurons after hypophysectomy.

PMID- 9147289
TI  - Endogenous neurotensin regulates hypothalamic-pituitary-adrenal axis activity and
      peptidergic neurons in the rat hypothalamic paraventricular nucleus.
AB  - Adrenocorticotropin (ACTH) secretion depends primarily on hypophysiotrophic
      factors released from neurons of the paraventricular nucleus of the hypothalamus.
      However, the neurochemical factors controlling these neurons, in particular
      neuropeptides, have had little investigation. In this study, we have investigated
      the role of neurotensin in the regulation of the different components of the
      hypothalamo-pituitary-adrenal (HPA) axis under basal and stress conditions in
      rats. For this purpose, animals were implanted with bilateral cannulae filled
      with crystals of the neurotensin antagonist, SR 48692, and which were located
      above the paraventricular nucleus. Five days after surgery, the effects of SR
      48692 implants were studied on basal and stress-induced secretion of ACTH and
      corticosterone. Such treatment did not modify plasma levels of ACTH and
      corticosterone in basal conditions but reduced ACTH but not corticosterone levels
      after tail cut procedure. After an exposure to a novel environment for 30 min,
      both ACTH and corticosterone plasma levels were reduced in the SR 48692-treated
      group. In situ hybridization studies revealed that chronic administration of SR
      48692 induced a significant reduction of CRF mRNA levels in the parvocellular
      division of the paraventricular nucleus of the hypothalamus. In addition, a 2
      fold increase in basal levels of plasma vasopressin associated with an increase
      in vasopressin mRNA levels in the magnocellular neurons of the paraventricular
      nucleus was also detected. Finally, the basal plasma levels of oxytocin were not
      affected by the same treatment. Taken together, these findings strongly suggest
      that endogenous neurotensin in the paraventricular nucleus plays a tonic
      stimulatory role on HPA axis activity and an inhibitory effect on vasopressin
      secretion.

PMID- 9147288
TI  - Concomitant up-regulation of proopiomelanocortin and dopamine D2-receptor gene
      expression in the pituitary intermediate lobe of the spontaneously hypertensive
      rat.
AB  - Alterations in central dopaminergic mechanisms in the Spontaneously Hypertensive
      Rat (SHR) have been previously implicated in the development of the hypertensive
      phenotype in this rat strain. We have examined the expression and regulation of
      the dopamine-responsive gene proopiomelanocortin (POMC) in the neurointermediate
      lobe (NIL) of the pituitary in both SHR and normotensive Wista Kyoto (WKY) rats.
      Solution hybridization/nuclease protection analysis showed that adult SHR express
      POMC mRNA in the NIL at approximately 2-4 times the level seen in normotensive
      WKY controls, associated with a concomitant 2-fold increase in dopamine D2
      receptor (D2-R) mRNA expression. Despite the obvious difference in D2-R gene
      expression, NIL POMC mRNA in both rat strains was regulated in an identical
      manner following 4 d in vivo bromocriptine or haloperidol treatment. In contrast,
      though D2-R mRNA expression in the WKY NIL was significantly up-regulated by D2-R
      blockade with haloperidol, the elevated levels of D2-R mRNA in the NIL of the
      hypertensive strain were not altered by D2-R antagonism. Following isolation from
      all hypothalamic input by 5 d in vitro culture, SHR melanotrophs exhibited a 2-3
      fold higher rate of beta EP secretion and POMC mRNA expression than melanotrophs
      derived from normotensive WKY rats, though beta EP secretion was inhibited in a
      similar fashion by the D2-R agonist quinpirole in both cultures. The current data
      demonstrate changes in expression of both POMC and D2-R mRNA in the SHR NIL which
      may be a consequence of altered dopaminergic input and/or alterations in D2-R
      regulation in this tissue, possibly enabling other factors in addition to
      dopamine to maintain the NIL of the SHR in a relatively hyperactive state.
      Whether or not POMC-derived peptides or other factors secreted from the
      melanotroph cell play any role in the development or maintenance of hypertension
      in this strain is yet to be established.

PMID- 9147290
TI  - Post-transcriptional regulation of the gonadotropin-releasing hormone gene in GT1
      7 cells.
AB  - GT1-7 cells respond to treatment with the phorbol ester, phorbol 12-myristate 13
      acetate (PMA), with an inhibition of transcription of the proGnRH gene and
      decreases in GnRH mRNA levels. However, the timing of this decrease in GnRH mRNA
      levels suggests that a decrease in GnRH mRNA stability may be involved in
      addition to an inhibition of transcription of the proGnRH gene. To address this
      possibility, we treated GT1-7 cells with 100 nM PMA for 4 h and then monitored
      GnRH mRNA levels over time after blockade of GnRH gene transcription with DRB.
      PMA treatment caused GnRH mRNA half-life to decrease from 30 to 11 h. Then, to
      verify this observation, we examined changes in GnRH mRNA poly (A) tail length,
      which may be a reflection of mRNA turnover, following treatment of GT1-7 cells
      with PMA or vehicle for 0, 4, 8 or 24 h. The poly (A) tail was removed from half
      of the GT1 cytoplasmic RNA sample by digestion with RNase H and the difference in
      GnRH mRNA size with and without RNase H treatment was determined by Northern
      hybridization. PMA treatment (4 and 8 h) resulted in a significant decrease in
      the length of the GnRH mRNA poly (A) tail, consistent with a decrease in GnRH
      mRNA stability. This finding suggests that GnRH mRNA turnover is inducible by
      substances such as PMA. Our study indicates that a change in mRNA stability is
      one of a multiplicity of levels at which GnRH gene expression is regulated.

PMID- 9147291
TI  - Effects of pituitary adenylate cyclase-activating polypeptide (PACAP) and
      vasoactive intestinal polypeptide (VIP) on hormone secretion from sheep pituitary
      cells in vitro.
AB  - Although vasoactive intestinal polypeptide (VIP) is thought to be a prolactin
      releasing factor, in vivo studies on sheep suggest that it is inactive in this
      species. Recent studies, based primarily on the rat, suggest that the related
      pituitary adenylate cyclase-activating polypeptide (PACAP) is also a
      hypophysiotrophic factor but again in sheep, this peptide has no in vivo effects
      on hormone secretion despite being a potent activator of adenylate cyclase in
      vitro. This lack of response to either peptide in vivo in sheep could be due to
      the low concentration of peptide that reaches the pituitary gland following
      peripheral injection. In the present study we therefore adopted an alternative
      approach of evaluating in vitro effects of these peptides on GH, FSH, LH or
      prolactin secretion from dispersed sheep pituitary cells. In a time-course study,
      PACAP (1 mumol/l) increased GH concentrations in the culture medium between 1 and
      4 h and again at 12 h but had no effect in the 6 and 24 h incubations. Prolactin,
      LH and FSH were not affected by PACAP. The response to various concentrations of
      PACAP (1 nmol/l-1 mumol/l) were then evaluated using a 3 h incubation. Again
      prolactin and LH were not affected by PACAP and there was a small increase in GH
      concentrations but only at high concentrations of PACAP (0.1 and 1 mumol/l; P <
      0.05). PACAP also stimulated FSH secretion in cells from some animals although
      this effect was small. The GH response to PACAP was inhibited by PACAP(6-38), a
      putative PACAP antagonist, but not by (N-Ac-Tyr1, D-Arg2)-GHRH(1-29)-NH2, a GH
      releasing hormone (GHRH) antagonist. The cAMP antagonist Rp-cAMPS was unable to
      block the GH response to PACAP suggesting that cAMP does not mediate the
      secretory response to this peptide. At incubation times from 1-24 h, VIP (1
      mumol/l) had no effects on prolactin, LH or GH secretion and, in a further
      experiment based on a 3 h incubation, concentrations of VIP from 1 nmol/l-1
      mumol/l were again without effect on prolactin concentrations. Interactions
      between PACAP and gonadotrophin releasing hormone (GnRH), GHRH and dopamine were
      also investigated. PACAP (1 nmol/l-1 mumol/l) did not affect the gonadotrophin or
      prolactin responses to GnRH or dopamine respectively. However, at a high
      concentration (1 mumol/l), PACAP inhibited the GH response to GHRH. In summary,
      these results show that PACAP causes a modest increase in FSH and GH secretion
      from sheep pituitary cells but only at concentrations of PACAP that are unlikely
      to be in the physiological range. The present study confirms that VIP is not a
      prolactin releasing factor in sheep.

PMID- 9147292
TI  - Differential effects of neuroactive steroids on somatostatin and dopamine
      secretion from primary hypothalamic cell cultures.
AB  - This study investigated the effects of neuroactive steroids, which have been
      reported to modulate GABA-ergic transmission, on the secretion of somatostatin
      (SRIH) and also dopamine (DA) from primary rat hypothalamic cell cultures, where
      the release of both substances is regulated by a GABAA receptor-mediated
      inhibitory tone. Pregnenolone sulphate (PS), a negative allosteric modulator at
      the GABAA receptor, enhanced SRIH secretion in a time and dose-dependent manner
      (10(-12)-10(-8) M). This effect was reversed by muscimol (10(-8) M) and enhanced
      by bicuculline (10(-6) M), thus supporting an action of PS at the GABAA receptor.
      The release of endogenously synthesized dopamine (DA) was, however, unaffected by
      PS. A number of other steroids were also tested for their potential actions on
      SRIH and DA secretion. Allopregnanolone had slight but significant stimulatory
      actions on SRIH secretion, whereas tetrahydro-deoxycorticosterone (TH-DOC)
      markedly stimulated SRIH secretion with a bell-shaped dose response curve
      resembling that found for PS. The release of DA was unaffected by these
      neuroactive steroids but, unlike SRIH, DA release was stimulated by
      dehydroepiandrosterone sulphate (DHEAS). The results support the view that
      neuroactive steroids may play an important role in regulating some aspects of
      neuroendocrine function and they also provide the first demonstration of
      differential activities of neuroactive steroids within the hypothalamus at low,
      physiologically relevant concentrations. The results also raise the possibility
      that certain hypothalamic neuronal populations may possess uniquely different
      GABAA receptors and that such mechanisms may contribute to the functional
      development of the neuroendocrine system.

PMID- 9147293
TI  - Unchanged amounts of vasopressin mRNA in the supraoptic and paraventricular
      nucleus during aging and in Alzheimer's disease.
AB  - The paraventricular (PVN) and supraoptic nucleus (SON) demonstrate a striking
      stability with respect to cell numbers during aging and Alzheimer's disease (AD).
      Vasopressin (AVP) neurons even become activated during aging as judged from
      several parameters for neuronal activity, such as increased AVP plasma levels,
      enlarged nucleolar as well as cell size and an increased size of the Golgi
      apparatus in AVP-neurons. The activation possibly occurs as compensation for an
      age-related loss of AVP-receptors in the kidney. As a specific marker for AVP
      synthesis, we used quantitative in situ hybridization and estimated total amounts
      of AVP-mRNA in the entire SON and PVN of 14 control subjects and 14 AD patients
      that were matched for age, fixation time, postmortem delay and storage time of
      the tissue in paraffin. Following quantification, no differences were observed in
      total amounts of AVP-mRNA in the SON or PVN between young and old controls or
      between young and old AD patients, nor between the entire group of controls and
      AD patients. A significant negative correlation was found between the volume of
      the AVP-mRNA signal in the AD SON and age while the total amount of mRNA remained
      the same. This suggests a redistribution of cells or cell compartments in aging.
      A significant positive relation in both SON and PVN of AD patients was found
      between storage time of the paraffin-embedded tissue and the total amount of AVP
      mRNA. A significant positive relation was present in the PVN, but not SON between
      pH of the cerebrospinal fluid, which is a marker for agonal state and the total
      amount of AVP mRNA. The present unchanged AVP-mRNA levels in SON and PVN confirm
      earlier observations on the stability of cell numbers in these nuclei in aging
      and AD. Although on the basis of other parameters, AVP-mRNA upregulation was
      expected, gradual, chronic stimulation over prolonged periods of time may,
      possibly, induce alternative mechanisms of regulation such as changes in
      translatability or in mRNA stability.

PMID- 9147294
TI  - Hypophysiotropic CRF neurons display a sustained immediate-early gene response to
      chronic stress but not to adrenalectomy.
AB  - Immediate-early genes (IEGs) are now widely used to identify neurons acutely
      activated by extracellular stimuli. Though challenge-induced IEG expression is
      typically transient, examples of sustained elevation have been reported,
      including in hypothalamic magnocellular neurosecretory neurons of osmotically
      challenged rats. Another chronic stimulus, adrenalectomy (ADX), targets
      parvocellular neurosecretory neurons in the paraventricular nucleus of the
      hypothalamus (PVH), resulting in a persistent elevation in the synthesis and
      secretion of corticotropin-releasing factor (CRF). In the present study we used
      hybridization histochemical methods to compare the effects of ADX on the
      induction over time of two independent IEG markers, c-fos and NGFI-B, in
      hypophysiotropic CRF neurons. The induction of both c-fos and NGFI-B mRNA was
      greatest 3 to 6 after ADX, diminished by 12 h, and no longer detectable at 24,
      48, 72 h, or 6 days after surgery. Immunohistochemical analyses using a Fos
      specific N-terminally directed antiserum also revealed Fos immunoreactivity (-ir)
      in the PVH at early time points (3 h), but not later than 12 h after ADX.
      Combined immuno- and hybridization histochemistry on tissue from 3 h ADX rats
      localized Fos-ir and NGFI-B mRNA to parvocellular CRF-expressing neurons, the
      majority of which expressed both Fos and NGFI-B. These early IEG responses,
      however, were not paralleled by increases in CRF mRNA, which was not
      significantly elevated until 48 h after ADX. In the chronically ADX rat, CRF
      neurons are capable of c-fos expression since animals subjected to an acute
      injection of hypertonic saline 5 days after ADX displayed a robust induction of
      Fos-ir in the parvocellular PVH. Furthermore, a chronic challenge, insulin
      induced hypoglycemia, provoked comparable c-fos mRNA and protein expression in
      CRF neurons in the PVH of ADX and sham-operated rats, which was observed both
      acutely (2 h) and chronically (5 days) after the onset of hypoglycemia. The
      maintenance of Fos expression in parvocellular CRF neurons following chronic
      hypoglycemia, but not ADX, suggests an involvement of distinct signaling pathways
      in the maintenance of hypophysiotropic neuron responses to chronic steroid
      withdrawal and stress.

PMID- 9147295
TI  - Estrogen and stress interact to regulate the hypothalamic expression of a human
      proenkephalin promoter-beta-galactosidase fusion gene in a site-specific and sex
      specific manner.
AB  - Gonadal steroids and physiological stressors affect the regulation of
      proenkephalin (PPE) gene expression in the paraventricular (PVN) and ventromedial
      (VMH) hypothalamic nuclei. To examine the effects of these modulators at the
      cellular level, the current study utilized a transgenic mouse line that expresses
      a human proenkephalin promoter/bacterial beta-galactosidase fusion gene (ENK-1).
      Previous studies have demonstrated that the regulatory sequences included in this
      transgene are sufficient to support appropriate transcriptional regulation of the
      reported gene in the PVN of male ENK-1 mice in response to stress. The present
      experimental paradigm was designed to examine possible interactions of sex and
      circulating estrogen levels with the opioid responses to acute systemic
      stressors, an intraperitoneal injection of hypertonic (1.5 M) or isotonic (0.15
      M) saline. Adult ENK-1 mice were gonadally intact, gonadectomized, or 21 days
      postpartum. Forty-eight hours before perfusion, castrated males and
      ovariectomized females received either 10 micrograms estradiol benzoate or oil
      vehicle and 4 animals per group received no further treatment. Six h before
      perfusion, remaining animals received a single intraperitoneal injection of
      either hypertonic or isotonic saline. Tissues were sectioned through the
      hypothalamus and processed for X-gal histochemistry. In the VMH of ovariectomized
      females that received isotonic saline, estrogen significantly elevated transgene
      expression. This effect was not seen in females that only received estrogen or in
      those that received the severe systemic stressor of a injection of hypertonic
      saline. Estrogen and stress did not interact to elevate transgene expression in
      the VMH of males. A different pattern of expression was observed in the PVN;
      injection of hypertonic saline induced transgene expression only in gonadally
      intact males and in castrated males given estrogen. These findings demonstrate
      that stress and estrogen have sex-specific and site-specific regulatory effects
      on the expression of a PPE promoter transgene in hypothalamic neurons.

PMID- 9147296
TI  - Complete dentures in the prosthetic rehabilitation of elderly persons: five
      different criteria to evaluate the need for replacement.
AB  - The purpose of this study was to examine the condition and functional properties,
      as well as adjustment and replacement needs, of 288 complete dentures worn by 144
      inhabitants of Helsinki over 75 years old. Five different criteria to evaluate
      the need for replacement were used: (I) criteria based on Oral Health Surveys
      Basic Methods (WHO, 1987); (II) criteria based only on the clinical data
      collected during the examination; (III) criteria based only on examiners'
      subjective opinion of the condition of the dentures; (IV) criteria based on
      clinical data as well as examiners' experience and consultation with the patient;
      (V) criteria based only on patients' subjective opinion. Depending on the
      evaluation method used, 10-84% of the dentures were judged to be in need of
      replacement. Strict objective evaluation methods produced the highest figures for
      replacement need, and method (I, WHO, 1987) the lowest. The most justifiable
      replacement percentage (26%) was achieved when the dentist assessed treatment
      need together with the patient. This study documents the multiple subjective and
      objective difficulties related to the wearing of complete dentures. The study
      also highlights the well-recognized importance of regular annual reexaminations
      for those wearing complete dentures and the assessment of need for adjustment of
      the dentures. It also demonstrates that successful treatment decisions cannot be
      made solely on the basis of clinical examination or a dentist's subjective
      opinion, but should be formulated in close consultation with the patient.

PMID- 9147297
TI  - The effect of chronic periodontal disease on human jaw muscles: a pilot study
      using computed tomography.
AB  - Patients with chronic periodontal disease sometimes complain of difficulty in
      masticating hard foods. Computed tomography (CT) was used to investigate the
      cross-sectional area (CSA) and density of the masseter and medial pterygoid
      muscles in a pilot study of 12 healthy female subjects aged 30-39 years. Six
      subjects (the 'diseased' group) had suffered from chronic periodontal disease and
      had, on average, 40% bone loss. Their disease had been treated by scaling and
      root planning and had remained clinically stable for at least 6 months before
      their inclusion in the study. The six age-matched 'control' subjects had no
      history of periodontal disease. All bone-loss measurements were evaluated as a
      percentage of root length. At defined scan planes, sections of both muscles were
      readily identified. Results from the 'diseased' group as compared with the
      'control' group revealed that in the former the CSA of masseter and medial
      pterygoid was reduced significantly by 25% and 10%, respectively. There were no
      significant differences in the X-ray density of both muscles between the two
      groups, which indicated a similar fibro-fatty content. These findings indicate a
      reduction in the masticatory force that may be utilized by patients with reduced
      periodontal support and may help explain their masticatory difficulties.

PMID- 9147298
TI  - Static and dynamic moduli of composite restorative materials.
AB  - A series of polymeric composite restorative materials cured by primary and
      secondary methods was examined by static and dynamic testing. The static modulus
      of elasticity, dynamic and modulus and glass-transition temperature were
      determined over a three-month period with the intention of characterizing monomer
      conversion. Heat and pressure curing of one material gave good conversion, but
      not all combinations of blue-light irradiation achieved full conversion. The use
      of a curing oven, whether as the primary or secondary mechanism did not result in
      a significant improvement in modulus. The use of a dynamic mechanical thermal
      analyser provided good data and this type of equipment is recommended for the
      characterization of polymeric materials.

PMID- 9147299
TI  - Permeability of dentine after Nd:YAG laser treatment: an in vitro study.
AB  - The purpose of this investigation was to determine the effects of Nd:YAG laser
      treatment on the permeability of dentine. Forty dentine discs were prepared by
      horizontal sectioning through the middle coronal third of freshly extracted non
      carious third molars. After the removal of the pulp the discs were finished with
      600 grit and divided into three test groups and one control group (n = 10). For
      the test group three different laser power settings were chosen: test group A: 3
      x 60 sec, 60 mJ; test group B: 3 x 60 sec, 90 mJ; test group C: 3 x 60 sec, 120
      mJ. No laser treatment was performed on the control group. In a two-chamber
      system the filtration rate of dentine tubules from an exactly defined area of the
      specimens was measured using a radioactive Ringer solution under a pressure of 30
      cm H2O. Permeability measurements were carried out three times prior to lasing,
      three times immediately following laser treatment and six times after the
      application of phosphoric acid. Analysis of variance showed a significant
      influence of the Nd:YAG laser treatment on the permeability of dentine (P <
      0.001). The mean quotient of non-treated control vs. lased dentine was 2.19 +/-
      0.86 for the 60 mJ beam, 1.49 +/- 0.88 for the 90 mJ beam, and 2.04 +/- 2.17 for
      the 120 mJ beam. Etching the lased surfaces had a statistically significant
      influence on the permeability of the dentine only in the 60 mJ group (P < 0.001).
      The data show that the Nd:YAG laser treatment often increases the permeability of
      smear layer covered dentine but moderates the increase of permeability after
      etching the surface with phosphoric acid.

PMID- 9147300
TI  - Effect of fluoride treatment on remineralization of bleached enamel.
AB  - The objective of the study was to evaluate the remineralizing capacity of
      different fluoride treatments on dental enamel bleached with carbamide peroxide
      (Opalescence). Sixty bovine enamel slabs were subjected to four cycles comprising
      bleaching (12 h) and remineralization in artificial saliva (8 h). The samples
      were evenly distributed among four groups (A-D). During the first hour of the
      remineralization period the specimens in Group A were covered with a fluoride
      varnish (Duraphat; 2.23% F-). In group B the enamel slabs were stored in a
      fluoride solution (0.2% F- as NaF) for 1 min prior to remineralization. Group C
      did not receive a fluoride treatment, and group D (control) was stored in
      distilled water instead of bleaching. Microhardness (VHN) was evaluated before
      the experiments and after the second and fourth cycle, respectively. Final
      hardness was calculated as percentage of the initial hardness. Analysis of
      variance was applied to the data followed by pairwise comparisons with corrected
      level of significance (P < 0.01). Hardness decreased significantly in groups A-C
      compared to the control group (D). The bleached and unfluoridated specimens
      (group C) showed a significantly higher hardness loss compared to the fluoridated
      specimens, whereas no significant difference was observed between the two
      fluoridated groups. It is concluded that remineralization of bleached enamel is
      improved by application of highly concentrated fluorides.

PMID- 9147301
TI  - Study of occlusal contact variability within individuals in a position of maximum
      intercuspation using the T-SCAN system.
AB  - Views on the reliability of the T-SCAN systems as a method for occlusal contact
      registration are contradictory. In this paper the tooth contacts of various
      patients in maximum intercuspation are analysed and their different bites
      compared using the time analysis mode of the T-SCAN. The findings show that
      within the same individual, no significant differences exist between the number
      of contacts on each tooth after four bites were performed in an MI position,
      except for teeth numbers 46, 44 and 41.

PMID- 9147303
TI  - The optimum curing cycle for a light- and heat-cured composite inlay material.
AB  - The transverse bend test and surface microhardness test were used to determine
      the optimum curing cycle for a light- and heat-cured composite inlay material.
      Specimens were light-cured (control) and light- and heat-cured using the
      following temperatures: 50 degrees C for 5 min; 50 degrees C for 10 min; 100
      degrees C for 1 min; 100 degrees C for 5 min; 100 degrees C for 10 min; and 100
      degrees C for 15 min. Heat-curing in boiling water at 100 degrees C for at least
      1 min significantly improved the transverse strength, modulus of elasticity and
      surface microhardness compared to light-curing only or at 50 degrees C. The
      curing cycle of 100 degrees C for 5 min is considered the most appropriate.

PMID- 9147302
TI  - Bonding of silver-palladium-copper-gold alloy with thiol derivative primers and
      tri-n-butylborane initiated luting agents.
AB  - This in vitro study elevated the effect of two primers on bond strengths and
      durability of luting agents joined to a silver-palladium-copper-gold alloy. One
      primer (Metal Primer) contained methacryloyloxyalkyl thiophosphate derivative
      (MEPS). The other primer (V-Primer) contained 6-(4-vinylbenzyl-n-propyl)amino
      1,3,5-triazine-2,4-dithiol (VTD). The luting agent was a methyl methacrylate
      (MMA)-based adhesive resin that contained 4-methacryloyloxyethyl trimellitate
      anhydride (4-META) and was initiated with tri-n-butylborane derivative (TBB). In
      order to evaluate the function of 4-META, MMA-TBB resin without 4-META was used
      as a control. The alloy specimens were bonded with six combinations of two
      primers and two luting agents. Shear bond strengths were determined before and
      after thermocycling. Both primers significantly elevated the bond strengths of
      the luting agents joined to the alloy. For unprimed groups, 4-META resin showed a
      more durable bond than did MMA-TBB resin. Combined use of Metal Primer with 4
      META resin reduced the bond strength, while combination of V-Primer and 4-META
      resin did not affect the bond strength.

PMID- 9147304
TI  - The influence of anterior guidance and condylar guidance on mandibular protrusive
      movement.
AB  - This study reveals the influence of the incisal and condylar guidance on
      mandibular protrusive movement. The protrusive movements were measured on 54
      young adults (27 females, 27 males) using a three-dimensional mandibular movement
      analysing system. The inclinations of the sagittal paths on the incisor, canine,
      1st molar, 2nd molar and condylar points were calculated, and multiple regression
      analysis was performed to evaluate the influence of the incisal and condylar
      paths on the path of each tooth quantitatively. The influence of the incisal path
      on any tooth path was consistently greater than that of the condylar path. The
      condylar path had a greater influence on the paths of posterior teeth than on the
      paths of anterior teeth, especially in the female subjects. The influence of the
      condylar path on the molar paths was twice as great in the female than that in
      the male subjects. It was concluded that the influence of the incisal and
      condylar guidance on the protrusive movement path varies according to the kind of
      tooth and the gender of the subject. These guiding system characteristics were
      confirmed by morphological analysis.

PMID- 9147305
TI  - Water sorption and solubility of resin-modified polyalkenoate cements.
AB  - The purpose of this study was to compare the water sorption and solubility of
      several resin-modified polyalkenoate cements. The materials evaluated included
      Variglass used as a restoration, base on liner; Fuji II LC, Fuji Liner;
      Vitrebond; Vitremer and Photac-Bond. Z100, a composite resin, was used as
      control. All specimens were manipulated according to the manufacturers'
      instructions and then subjected to water sorption and solubility tests based on
      the ISO 4049 requirements. Data were subjected to one-way ANOVA and Duncan's test
      at a 0.05 significance level. Results show that the composite resin control had
      significantly less water sorption than any of the resin-modified polyalkenoate
      cements evaluated. The degree of water sorption was product dependent and
      appeared to be influenced by the resin (HEMA) content. There was no apparent
      correlation between water sorption and solubility. Some of the resin-modified
      polyalkenoate cements retained water in their set structure and hence solubility
      could not be assessed.

PMID- 9147306
TI  - Relationship between size of denture foundation area and resorption of alveolar
      ridge in the edentulous mandible.
AB  - The relationship between the size of the denture foundation area and the
      resorption of the alveolar ridge was investigated in 55 edentulous subjects. The
      denture foundation area was recorded using a modelling compound impression
      technique with border moulding. Both sides of each edentulous mandible were
      examined separately, making a total of 110 experimental sides in the study. On a
      stone cast made from each impression, the size of of the superficial denture
      foundation area and of the projected denture foundation area on the tentative
      plane of occlusion of each anatomical zone were measured. The vertical height of
      the alveolar ridge at the lateral incisor and first molar region was also
      evaluated. The size of the superficial denture foundation area in the antero
      lingual and postero-lingual zones showed no significant correlation with the
      degree of alveolar ridge resorption. The size of the projected denture foundation
      area on the tentative plane of occlusion in the anterior section showed negative
      significant correlation with the degree of alveolar ridge resorption. The size of
      the projected denture foundation area on the tentative plane of occlusion in the
      posterior section showed no significant correlation with the degree of alveolar
      ridge resorption.

PMID- 9147307
TI  - The response of human premolars to cyclic loading.
AB  - The aim of the study was to obtain data on the dynamic strength of both intact
      and prepared premolars for partial veneer crowns. Cyclic loading was performed in
      a modified Amslers high-frequency pulsator with varying force (between 400 and
      1400 N). The greatest dynamic strength was exhibited by the intact samples. The
      greater the load the fewer the cycles necessary to fracture the tooth. A
      statically significant difference was found (P < 0.05) between the magnitude of
      cyclic loads and the different types of specimens tested.

PMID- 9147308
TI  - Solution conformation of N-terminal fragments of trichosanthin small domain (TCS
      182-200). Circular dichroic studies.
AB  - Three peptides, T14, T18 and TDK, derived from the N-terminus of trichosanthin
      small domain (TCS 182-200) have been investigated by circular dichroism.
      Secondary structure and structural transitions of the above peptides under
      different conditions were studied. Alcohol prompts a transition of the T18
      peptide from a beta-sheet to an alpha-helical structure. It also increases the
      alpha-helicities of T14 and TDK. The beta-sheet of T18 peptide appears more
      hydrophobic than the alpha-helix of T14 or TDK. The effects of polypeptide
      sequence and solvent on secondary structure formation of these model peptides are
      discussed.

PMID- 9147309
TI  - Prediction of beta-turns.
AB  - A residue-coupled model is proposed to predict the beta-turns in proteins. The
      rates of correct prediction for the 455 beta-turn tetrapeptides and 3807 non-beta
      turn tetrapeptides in the training database are 94.7 and 81.3%, respectively. The
      rates of correct prediction for the 110 beta-turn tetrapeptides and 30,229 non
      beta-turn tetrapeptides in the testing database are 80.0 and 80.2%, respectively.
      Compared with the rates of correct prediction based on the residue-independent
      model reported previously, the quality of prediction is significantly improved by
      the new model, implying that the residue-coupled effect along a polypeptide chain
      is important for the formation of reversal turns, such as beta-turns, during the
      process of protein folding.

PMID- 9147310
TI  - Molecular mechanics studies on dipeptide models of diphenylalanine and its
      derivatives.
AB  - As a part of our studies on the structure and conformations of peptidomimetics,
      we present conformational energy calculations on model peptides with (a) diphenyl
      alanine and its tricyclic derivatives and (b) triphenyl alanine residues using
      molecular mechanics and conformational analysis methods. The energies are
      calculated as a function of the backbone torsions (phi and psi), and the results
      are presented in terms of isoenergy contours in the phi-psi space. The low-energy
      models adopt conformations characteristic of a variety of regular structures such
      as the alpha-helix, gamma-turn and polyproline-II-type three- and four-fold
      helices. The conformational preferences in the model peptides with diphenyl
      alanine and its tricyclic derivatives are sensitive to the side-chain torsion,
      with some similarities to the corresponding preferences of L-Ala dipeptide. The
      energy profile of the model peptide with triphenyl alanine is similar to that of
      the model peptide with Tle (tert-leucine) residue. The results of our studies
      have implications in the design of conformationally constrained peptidomimetics
      with structures in the beta- and alpha-helical regions.

PMID- 9147311
TI  - A quantitative structure-activity relationship study of some substance P-related
      peptides. A multivariate approach using PLS and variable selection.
AB  - Nine new analogues of substance P (SP) were designed using quantitative sequence
      activity models based on the amino acid z-scales with PLS as the statistical
      method and the GOLPE procedure for variable selection. The nine SP analogues were
      synthesised by solid-phase peptide synthesis and tested for affinity to the NK-1
      receptor from rat brain with radio receptor assay using [125I]-Bolton-Hunter
      substance P as labelled ligand. All of the new substance P analogues showed high
      affinities, with IC50 values of less than 0.8 nM. One analog, Lys-Arg-Ala-Lys-Phe
      Met-Met-Phe-Phe-Gly-Leu-Let-NH2, showed a exceptional high affinity for the NK1
      receptor, with IC50 = 5 pM.

PMID- 9147312
TI  - Synthesis and NMR spectroscopy of peptides containing either phosphorylated or
      phosphonylated cis- or trans-4-hydroxy-L-proline.
AB  - Many proteins are regulated by reversible O-glycosylation and O-phosphorylation.
      Whereas O-glycosylation of hydroxy-L-proline is common and well investigated,
      phosphorylation has not been proved so far in vivo, but this post-translational
      modification is entirely possible. As a first step to identify this phosphoamino
      acid, we describe both the syntheses of peptides phosphorylated at 4-hydroxy-L
      proline and the 1H and 31P NMR parameters of these phosphopeptides. The model
      peptides were synthesized on solid-phase using Fmoc-strategy. Both natural
      isomers of 4-hydroxy-L-proline (containing the hydroxyl group in either the cis
      or trans position) were introduced without side-chain protection. All peptides
      were globally phosphorylated with O,O'-tert-butyl-N,N-diethylphosphoramidite on
      the solid phase and cleaved with trifluoroacetic acid. Additionally, we
      synthesized two classes of phosphonopeptides that mimic phosphopeptides, namely H
      and methylphosphonopeptides. The NMR data were based on the model peptide Gly
      Gly-Hyp-Ala, which is regarded as a typical random-coil sequence. The NMR
      parameters showed a significant influence of the phosphate group on the cis-trans
      isomerization of the Gly-Hyp bond, which may reflect a possible regulation of
      proteins by changing their local conformations. The 1H and 31P NMR parameters
      differed for each isomer, and were distinct from the parameters of phosphorylated
      serine, threonine and tyrosine. These known shifts can be used to identify both
      cis- and trans-O-phospho-4-hydroxy-L-proline in vivo.

PMID- 9147313
TI  - A peptide derivative (1-70 fragment) of protein SV-IV accelerates human blood
      coagulation in vitro by selective inhibition of the heparin-induced antithrombin
      III activation process.
AB  - The effect of two peptide derivatives of the rat SV-IV (SV-IV/A: 1-70 fragment;
      SV-IV/B: 71-90 fragment) on human blood coagulation was investigated. The SV-IV/A
      fragment was found to possess the same procoagulant activity of the native
      protein, whereas SV-IV/B retained only a very small fraction of the activity. The
      results obtained strongly suggest that the procoagulant activity of SV-IV/A is
      due, like SV-IV, to a selective inhibition of the antithrombin III (AT III)
      activation process induced by heparin, an essential cofactor of AT III. The main
      data supporting this hypothesis are the following: 1) the concentration of active
      serum AT III decreases when SV-IV/A is present in the clotting system; 2) the
      plasma treatment with SV-IV/A reduces the concentration of AT III, but not that
      of other plasma serine protease inhibitors; 3) the recalcification time (RT) of
      the plasma treated with a rabbit anti-AT III polyclonal antiserum is not modified
      by SV-IV/A; 4) the presence of SV-IV/A in a reaction mixture containing pure
      fibrinogen, alpha-thrombin, heparin, and AT III neutralizes the thrombin
      inhibition induced by AT III; 5) the concentration of the thrombin-AT III
      complexes, occurring in sera obtained from CaCl2-coagulated plasma, is markedly
      reduced in the presence of SV-IV/A; 6) appropriate concentrations of heparin
      neutralize the inhibitory effect of either SV-IV/A or SV-IV on the AT III
      activity in vitro.

PMID- 9147314
TI  - alpha-Amino acids derived from ornithine as building blocks for peptide
      synthesis.
AB  - Recently great interest has arisen in the synthesis of combinatorial libraries,
      and this technology provides a significant partner to contemporary strategies in
      rational design and lead discovery. By simple combination of a given set of
      building blocks, high numbers of different molecules are produced simultaneously,
      increasing the possibility of discovery of a lead compound in a limited time. One
      direction of research in this field focuses on the synthesis of libraries
      composed of modified amino acids. Here, the synthesis and characteristics of some
      building blocks derived from ornithine are described. The synthesis is based on
      the acylation/sulfonation of the copper complex of ornithine by aroyl and
      arylsulfonyl chlorides exemplified by 2-thiophenecarbonyl chloride, p
      toluenesulfonyl chloride and 8-quinolinesulfonyl chloride. To evaluate the
      potential use of these modified alpha-amino acids as component in an oligopeptide
      library, all three derivatives were incorporated in a hexapeptide with a random
      sequence using a standard coupling procedure (DIC/HOBt/DIEA). Depending upon the
      acidity of the amido hydrogen on the delta-nitrogen, competition between
      intramolecular cyclization and peptide bond formation was observed. The higher
      the acidity, the more pronounced is this side reaction. Coupling conditions for
      peptide formation were optimized so that the newly described amino acid based
      building blocks are suitable for incorporation into libraries consisting of
      unnatural amino acids. The outlined procedures open up a broad avenue of
      possibilities for creation of diversity into peptidic libraries.

PMID- 9147315
TI  - Disinhibition and brain rhythms.

PMID- 9147316
TI  - Oxytocin and vasopressin neurones: vive la difference!

PMID- 9147317
TI  - Ca2+ release-induced inactivation of Ca2+ current in rat ventricular myocytes:
      evidence for local Ca2+ signalling.
AB  - 1. Inactivation of Ca2+ current (ICa) induced by Ca2+ release from sarcoplasmic
      reticulum (SR) was studied in single rat ventricular myocytes using whole-cell
      patch-clamp and indo-1 fluorescence measurement techniques. 2. Depolarizing
      pulses to 0 mV elicited large Ca2+ transients and ICa with biexponential
      inactivation kinetics. Varying SR Ca2+ loading by a 20 s pulse of caffeine showed
      that the fast component of ICa inactivation was dependent on the magnitude of
      Ca2+ release. 3. Inactivation of ICa induced by Ca2+ release was quantified,
      independently of voltage and Ca2+ entry, using a function termed fractional
      inhibition of ICa (FICa). The voltage relation of FICa had a negative slope,
      resembling that of single-channel Ca2+ current (iCa) rather than the bell-shaped
      current-voltage (I-V) relation of macroscopic ICa and Ca2+ transients. 4.
      Intracellular dialysis of myocytes with 10 mM EGTA (150 nM free [Ca2+]) had no
      effect on ICa inactivation induced by Ca2+ release, despite abolition of Ca2+
      transients and cell contraction. Dialysis with 3 or 10 mM BAPTA (180 nM free
      [Ca2+]) attenuated FICa in a concentration-dependent manner, with greater
      inhibition at positive than at negative potentials, consistent with more
      effective buffering of Ca2+ microdomains of smaller iCa. 5. Spatial profiles of
      [Ca2+] near an opened Ca2+ channel were simulated. [Ca2+] reached submillimolar
      levels at the mouth of the channel, and dropped steeply as radial distance
      increased. At any given distance from the channel, [Ca2+] was higher at negative
      than at positive potentials. The radii of Ca2+ microdomains were significantly
      reduced by 3 or 10 mM BAPTA, but not by 10 mM EGTA. 6. In conclusion, the
      distinctive voltage dependence and susceptibility of Ca2+ release-induced ICa
      inactivation to fast and slow Ca2+ buffers suggests that the process is mediated
      through local changes of [Ca2+] in the vicinity of closely associated Ca2+
      channels and ryanodine receptors.

PMID- 9147318
TI  - Dual effects of tetracaine on spontaneous calcium release in rat ventricular
      myocytes.
AB  - 1. Confocal microfluorometry was used to study the effects of tetracaine on
      spontaneous Ca2+ release from the sarcoplasmic reticulum (SR) in isolated rat
      ventricular myocytes. 2. At low concentrations (0.25-1.25 mM), tetracaine caused
      an initial inhibition of spontaneous release events (Ca2+ sparks) and Ca2+ waves,
      which was followed by a gradual increase in Ca2+ release activity. The frequency
      and magnitude of sparks were first decreased and then increased with respect to
      control levels. At high concentrations (> 1.25 mM), tetracaine abolished all
      forms of spontaneous release. 3. Exposure of the myocytes to tetracaine resulted
      in a gradual increase in the SR Ca2+ load as indexed by changes in the magnitude
      of caffeine-induced Ca2+ transients. 4. In cardiac SR Ca(2+)-release channels
      incorporated into lipid bilayers, tetracaine (> 0.25 mM) induced a steady
      inhibition of channel activity. Addition of millimolar Ca2+ to the luminal side
      of the channel caused an increase in channel open probability under control
      conditions as well as in the presence of various concentrations of tetracaine. 5.
      We conclude that the primary effect of tetracaine on SR Ca(2+)-release channels
      is inhibition of channel activity both in vitro and in situ. The ability of
      tetracaine to reduce spark magnitude suggests that these events are not due to
      activation of single channels or non-reducible clusters of channels and,
      therefore, supports the multichannel origin of sparks. We propose that the
      paradoxical late potentiation of release by submaximal concentrations of
      tetracaine is caused by a gradual increase in SR Ca2+ load and subsequent
      activation of the Ca(2+)-release channels by Ca2+ inside the SR.

PMID- 9147319
TI  - Protein kinase C requirement of Ca2+ channel stimulation by intracellular ATP in
      guinea-pig basilar artery smooth muscle cells.
AB  - 1. Smooth muscle cells were isolated from guinea-pig basilar artery and
      conventional whole-cell recordings of Ca2+ channel activity were made at room
      temperature within 7 h of the isolation procedure. The purpose of the study was
      to investigate the mechanism of the stimulatory action of intracellular ATP on
      Ca2+ channels. 2. High (millimolar) concentrations of ATP were needed to produce
      stimulation of Ca2+ channels, and neither ADP nor AMP mimicked the action of ATP.
      3. The ATP effect was not mimicked by stable ATP derivatives (AMP-PNP or AMP-PCP)
      and was abolished by incubation of cells in non-specific protein kinase
      inhibitors (staurosporine or H-7) or specific protein kinase C inhibitors
      (GF109203x, calphostin C or chelerythrine) but not by tyrosine kinase inhibitors
      (tyrphostin B42 and genistein). 4. The data suggest that ATP-induced stimulation
      of L-type Ca2+ channels requires functional activity of a protein kinase C
      isozyme.

PMID- 9147320
TI  - Stimulation of pulmonary C fibres by lactic acid in rats: contributions of H+ and
      lactate ions.
AB  - 1. The contributions of H+ and lactate ions to the stimulation of single
      pulmonary C fibres by lactic acid were examined in anaesthetized and artificially
      ventilated rats. 2. Lactic acid injected into the right atrium caused a transient
      decrease in arterial blood pH (pHa) and a short but intense burst of afferent
      activities in pulmonary C fibres, whereas sodium lactate had no effect. The fibre
      activity usually reached a peak within 1-1.5 s, with an onset latency of < 1 s,
      and returned to the baseline in 5 s. 3. The injection of hydrochloric acid at the
      same pH as that of lactic acid did not significantly decrease pHa, nor did it
      stimulate any C fibres studied. 4. Formic acid has a pKa value (the negative
      logarithm of the dissociation constant) almost identical to that of lactic acid;
      thus, its injection decreased pHa to the same degree as did the injection of
      lactic acid. However, the response of C fibres to lactic acid was 134% stronger
      than that to formic acid. 5. We conclude that H+ is primarily responsible for the
      activation of pulmonary C fibres by lactic acid, probably through a direct effect
      of H+ on these afferent endings. The lactate ion, by itself, does not activate C
      fibres, but it seems to potentiate the stimulatory effect of H+ on these
      afferents.

PMID- 9147321
TI  - Endothelial-derived superoxide anions in pig coronary arteries: evidence from
      lucigenin chemiluminescence and histochemical techniques.
AB  - 1. The generation of superoxide anions (O2-) by intact pig coronary artery rings
      was measured using a lucigenin-enhanced chemiluminescence technique and a
      histochemical technique with Nitroblue Tetrazolium (NBT) staining. 2. Isolated
      arteries with intact endothelium generated O2- at a rate of 9.0 +/- 0.8 pmol min
      1 (mg dry weight)-1; this rate was diminished by about 24% when the endothelium
      was removed. The NBT staining of arterial ring preparations showed formazan
      precipitation mainly in the intima. Arterial rings were pretreated with
      diethylthiocarbamate in order to inhibit Cu-Zn superoxide dismutase (SOD)
      activity which increased the O2- generation by 184 +/- 55% (n = 10; P < 0.01).
      Stimulation of protein kinase C with phorbol 12-myristate 13-acetate (5 microM)
      enhanced endothelium-dependent O2- generation by 136 +/- 20% (n = 19; P < 0.01).
      Neither stimulation with bradykinin or substance P, nor inhibition with NG-nitro
      L-arginine methyl ester of endothelial nitric oxide synthase had a significant
      effect on O2- generation. In contrast, the inhibition of flavoproteins with
      diphenyliodonium decreased concentration-dependent O2- generation (IC50, 1.85 +/-
      5.33 microM). Inhibition of tetrahydrobiopterin synthesis with 2,4-diamino-6
      hydroxy-pyrimidine resulted in a reduced generation of O2- by about 55%. 3. The
      addition of 100 microM NADH and 100 microM NADPH resulted in an excessive
      generation of O2- at a rate of 0.68 +/- 0.03 and 0.26 +/- 0.01 nmol O2- min-1 (mg
      protein)-1, respectively, in the membrane fraction, but not in the cytosolic
      fraction, of homogenates obtained from arteries. 4. The results suggest that
      intact coronary arteries do generate O2- under basal conditions and that the
      endothelial layer significantly contributes to this phenomenon. This generation
      of O2- is greatly influenced by intrinsic SOD activity. It is suggested that
      basal vascular O2- generation is mainly due to membrane-bound NAD(P)H oxidase
      activity and/or tetrahydrobiopterin-dependent processes.

PMID- 9147322
TI  - The immunophilin FK506-binding protein modulates Ca2+ release channel closure in
      rat heart.
AB  - 1. The nature of the signal that terminates the release of Ca2+ from the cardiac
      sarcoplasmic reticulum has remained elusive. This study was intended to examine
      whether FK506-binding protein (FKBP), which is tightly associated to the
      ryanodine receptor (RyR)/Ca2+ release channel, plays a role in the termination of
      Ca(2+)-induced Ca2+ release (CICR) in heart. 2. Confocal microscopy and the Ca2+
      indicator fluo-3 were used to visualize the elementary release events, i.e. 'Ca2+
      sparks' in rat ventricular myocytes under resting or voltage-clamped conditions.
      Additionally, electrophysiological single-channel recordings, at constant [Ca2+]
      or during [Ca2+] steps produced by photorelease of caged Ca2+, were obtained from
      rat cardiac RyRs incorporated in planar lipid bilayers. 3. Inhibition of FKBP by
      the immunosuppressants FK506 or rapamycin increased the duration of spontaneous
      or depolarization-evoked Ca2+ sparks 6- to 7-fold. In addition, Ca2+ sparks were
      seen with two-level amplitudes, corresponding to full and half normal spark
      amplitude. 4. FK506 potentiated and prolonged electrically stimulated [Ca2+]i
      transients and contractions, but did not affect the amplitude and kinetics of the
      L-type Ca2+ channel current. 5. In planar lipid bilayers, FK506 (15 microM)
      prolonged approximately 7-fold the mean open lifetime of reconstituted single
      RyRs, induced the appearance of long-lasting subconductance states, and markedly
      slowed the spontaneous decay of RyR activity elicited by fast and sustained Ca2+
      stimuli. The time constant of the spontaneous decay of activity increased from
      1.8 s in control to > or = 20 s in the presence of FK506. 6. We conclude that
      FKBP may afford an intrinsic mechanism to terminate RyR openings and it may thus
      exert a negative feedback on CICR in heart cells.

PMID- 9147323
TI  - K+ accumulation and K+ conductance inactivation during action potential trains in
      giant axons of the squid Sepioteuthis.
AB  - 1. During action potential trains in giant axons from the squid Sepioteuthis,
      decline of the peak level of the undershoot potential was observed. The time
      course of the decline of the undershoot could be fitted with a three-exponential
      function with time constants of approximately 25, approximately 400 and
      approximately 7,000 ms, respectively. 2. When the osmolarity of the external
      solution was doubled by adding glucose (1.2 M), the fast component of undershoot
      decline, but not the medium and slow components, was significantly reduced. 3.
      Under voltage clamp in high osmolarity solutions where K+ accumulation was
      completely removed, repeated depolarizing pulses at 40 Hz (designed to mimic a
      train of action potentials) elicited K+ currents whose peak value declined. The
      decline is consistent with inactivation of the K+ conductance (gK). The decline
      of gK was fitted by a two-exponential function with time constants of
      approximately 400 and approximately 7,000 ms, respectively. 4. Interventions
      designed to modify Schwann cell physiology, such as high frequency stimulation
      (100 Hz, 2 min), externally applied ouabain (100-500 microM), L-glutamate (100
      microM), ACh (100 microM), Co2+ (5mM), Ba2+ (2mM), or removal of external Ca2+ by
      EGTA, had no significant effects on the fast, medium or slow components of
      undershoot decline. 5. The results suggest that the fast component of undershoot
      decline represents K+ accumulation in the space between Schwann cell and
      axolemma. The medium and slow components are the result of axonal gK
      inactivation. Schwann cells appear to be involved in K+ clearance only to the
      extent that they provide an efficient physical pathway for the clearance of K+ by
      extracellular diffusion.

PMID- 9147324
TI  - Antagonists of the cGMP-gated conductance of vertebrate rods block the
      photocurrent in scallop ciliary photoreceptors.
AB  - 1. Hyperpolarizing scallop photoreceptors, like vertebrate rods, use cGMP as an
      internal messenger and their light-sensing structure is also of ciliary origin.
      To ascertain possible functional similarities between the light-sensitive
      conductances in the two classes of visual cells, we examined in scallop
      photoreceptors the effects of several antagonists of the photocurrent of rods. 2.
      Extracellular application of L-cis-diltiazem rapidly and reversibly suppressed
      the photocurrent. The effect was stereospecific and dose dependent, with a K1/2
      of approximately 400 microM. Intracellular dialysis at lower doses (100-200
      microM) also induced a substantial inhibition. 3. L-cis-Diltiazem reduced the
      light-activated conductance without shifting the intensity-response curve.
      Furthermore, the drug also blocked the current directly evoked by application of
      cGMP. These observations indicate that the inhibitory effects result from
      blockage of the conductance, rather than from impairment of the activating
      cascade. 4. The fractional blockage increased e-fold per approximately 55 mV
      depolarization, regardless of the side of drug application, as if the charged
      form of L-cis-diltiazem can only access the blocking site from the intracellular
      compartment. 5. The amiloride derivative 3',4'-dichlorobenzamil potently
      suppressed the photocurrent (K1/2 approximately 5 microM), without affecting its
      kinetics or operating range. Amiloride itself was also effective at higher
      concentrations. 6. The pharmacological resemblance of these light-dependent
      channels to those of rods and cones indicates that significant aspects of the
      transduction cascade are conserved across disparate sensory cells of ciliary
      origin.

PMID- 9147325
TI  - Mechanisms involved in increased iron uptake across rat duodenal brush-border
      membrane during hypoxia.
AB  - 1. Chronic hypoxia enhances intestinal iron transport but the cellular processes
      involved are poorly understood. In order to assess the effects of 3 days of
      hypoxia on iron uptake across the duodenal brush-border membrane, we have
      measured the membrane potential difference (Vm) of villus-attached enterocytes by
      direct microelectrode impalement and have used semi-quantitative autoradiography
      to study changes in expression of iron uptake during enterocyte maturation. 2.
      Hypoxia increased duodenal Vm (-57.7 vs. -49.3 mV, P < 0.001). Ion substitution
      experiments revealed that hyperpolarization was due, at least in part, to a
      reduction in brush-border Na+ permeability. 3. Autoradiography revealed that
      hypoxia increased by 6-fold the rate of iron accumulation during enterocyte
      transit along the lower villus and enhanced by 3-fold the maximal accumulation of
      iron. Depolarization of the brush border, using a high-K(+)-containing buffer,
      caused a proportionally greater reduction in iron uptake in control compared with
      hypoxic tissue suggesting that the raised iron uptake is only partly driven by
      brush-border hyperpolarization. 4. We conclude that hypoxia increases the
      expression of iron transport in duodenal brush-border membrane and an enhanced
      electrical driving force may be involved in this response.

PMID- 9147326
TI  - pH gradient effects on chloride transport across basolateral membrane vesicles
      from guinea-pig jejunum.
AB  - 1. The effects of alkaline-inside pH gradients on 36Cl- uptake were quantified by
      using brush-border membrane (BBM) and basolateral membrane (BLM) vesicles from
      guinea-pig jejunum. 2. With BBM vesicles, a pHo/pHi gradient of 5.0/7.5 yielded
      fast overshoots involving a random, non-obligatory Cl(-)-H+ symport, strongly
      inhibited by CCCP. In contrast, BLM vesicles responded to similar pH gradients
      with much smaller, delayed overshoots, unaffected by CCCP. 3. The initial Cl-
      entry rates into BLM vesicles were a function of each pHo, pHi and delta pH
      value. They were stimulated by valinomycin in the presence of inward-directed K+
      gradients. Short-circuiting the membrane potential with equilibrated K+ and
      valinomycin inhibited pH gradient-dependent Cl- uptake, but only partially. 4.
      Taken together, these results indicate that guinea-pig jejunal BLM vesicles
      possess both Cl- conductance and Cl(-)-H+ symport activities. 5. Even when
      different, the BBM and the BLM symporters are mechanistically similar. Neither of
      them involves a Cl(-)-OH- antiport, nor a simultaneous Cl(-)-anion exchange
      mechanism. Rather, for each membrane, all of these activities (symport, anion
      exchange) can be explained in terms of a single mobile carrier acting as a
      random, non-obligatory Cl(-)-H+ symporter where exchange occurs simply by
      counterflow. Net Cl- translocation via either the ternary (Cl(-)-C-H+) or the
      binary (Cl(-)-C) complexes accounts, respectively, for the existence of two,
      operationally distinct, electroneutral and rheogenic components. 6. The BBM
      symporter appears to involve an AE2 protein, but the molecular identity of the
      BLM one remains to be established.

PMID- 9147327
TI  - Synapse-selective impairment of NMDA receptor functions in mice lacking NMDA
      receptor epsilon 1 or epsilon 2 subunit.
AB  - 1. We have explored the effects of targeted disruption of the N-methyl-D
      aspartate (NMDA) receptor epsilon 1 or epsilon 2 subunit gene on NMDA receptor
      mediated excitatory postsynaptic currents (NMDA EPSCs) and long-term
      potentiations (LTPs) at the two types of synapse in mouse hippocampal CA3
      pyramidal neurons: those formed by the commissural/associational (C/A) and
      fimbrial (Fim) inputs. 2. Electrophysiological experiments were performed in
      hippocampal slices prepared from both wild-type and epsilon 1- or epsilon 2
      disrupted mice using extracellular and whole-cell patch recording techniques. To
      assess the epsilon 1, epsilon 2 and zeta 1 subunit expression at cellular levels,
      we performed non-isotopic in situ hybridization with digoxigenin-labelled cRNA
      probes. 3. We could record EPSCs in response to the stimulations to either of the
      C/A and Fim afferents from a single CA3 pyramidal neuron. The epsilon 1, epsilon
      2 and zeta 1 subunits were expressed together in individual CA3 neurons. 4. The
      epsilon 1 subunit disruption selectively reduced NMDA EPSCs and LTP in the C/A
      CA3 synapse without significantly affecting those in the Fim-CA3 synapse, whereas
      the epsilon 2 subunit mutation diminished NMDA EPSCs and LTP in the Fim-CA3
      synapse with no appreciable functional modifications in the C/A-CA3 synapse. 5.
      These results suggest that NMDA receptors with different subunit compositions
      function within a single CA3 pyramidal cell in a synapse-selective manner.

PMID- 9147328
TI  - Physiology and anatomy of synaptic connections between thick tufted pyramidal
      neurones in the developing rat neocortex.
AB  - 1. Dual voltage recordings were made from pairs of adjacent, synaptically
      connected thick tufted layer 5 pyramidal neurones in brain slices of young rat
      (14-16 days) somatosensory cortex to examine the physiological properties of
      unitary EPSPs. Pre- and postsynaptic neurones were filled with biocytin and
      examined in the light and electron microscope to quantify the morphology of
      axonal and dendritic arbors and the number and location of synaptic contacts on
      the target neurone. 2. In 138 synaptic connections between pairs of pyramidal
      neurones 96 (70%) were unidirectional and 42 (30%) were bidirectional. The
      probability of finding a synaptic connection in dual recordings was 0.1. Unitary
      EPSPs evoked by a single presynaptic action potential (AP) had a mean peak
      amplitude ranging from 0.15 to 5.5 mV in different connections with a mean of 1.3
      +/- 1.1 mV, a latency of 1.7 +/- 0.9 ms, a 20-80% rise time of 2.9 +/- 2.3 ms and
      a decay time constant of 40 +/- 18 ms at 32-24 degrees C and -60 +/- 2 mV
      membrane potential. 3. Peak amplitudes of unitary EPSPs fluctuated randomly from
      trial to trial. The coefficient of variation (c.v.) of the unitary EPSP
      amplitudes ranged from 0.13 to 2.8 in different synaptic connections (mean, 0.52;
      median, 0.41). The percentage of failures of single APs to evoke a unitary EPSP
      ranged from 0 to 73% (mean, 14%; median, 7%). Both c.v. and percentage of
      failures decreased with increasing mean EPSP amplitude. 4. Postsynaptic glutamate
      receptors which mediate unitary EPSPs at -60 mV were predominantly of the L-alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor type. Receptors of
      the N-methyl-D-aspartate (NMDA) type contributed only a small fraction (< 20%) to
      the voltage-time integral of the unitary EPSP at -60 mV, but their contribution
      increased at more positive membrane potentials. 5. Branching patterns of
      dendrites and axon collaterals of forty-five synaptically connected neurones,
      when examined in the light microscope, indicated that the axonal and dendritic
      anatomy of both projecting and target neurones and of uni- and bidirectionally
      connected neurones was uniform. 6. The number of potential synaptic contacts
      formed by a presynaptic neurone on a target neurone varied between four and eight
      (mean, 5.5 +/- 1.1 contacts; n = 19 connections). Synaptic contacts were
      preferentially located on basal dendrites (63%, 82 +/- 35 microns from the soma,
      n = 67) and apical oblique dendrites (27%, 145 +/- 59 microns, n = 29), and 35%
      of all contacts were located on tertiary basal dendritic branches. The mean
      geometric distances (from the soma) of the contacts of a connection varied
      between 80 and 585 microns (mean, 147 microns; median, 105 microns). The
      correlation between EPSP amplitude and the number of morphologically determined
      synaptic contacts or the mean geometric distances from the soma was only weak
      (correlation coefficients were 0.2 and 0.26, respectively). 7. Compartmental
      models constructed from camera lucida drawings of eight target neurones showed
      that synaptic contacts were located at mean electrotonic distances between 0.07
      and 0.33 from the soma (mean, 0.13). Simulations of unitary EPSPs, assuming
      quantal conductance changes with fast rise time and short duration, indicated
      that amplitudes of quantal EPSPs at the soma were attenuated, on average, to <
      10% of dendritic EPSPs and varied in amplitude up to 10-fold depending on the
      dendritic location of synaptic contacts. The inferred quantal peak conductance
      increase varied between 1.5 and 5.5 nS (mean, 3 nS). 8. The combined
      physiological and morphological measurements in conjunction with EPSP simulations
      indicated that the 20-fold range in efficacy of the synaptic connections between
      thick tufted pyramidal neurones, which have their synaptic contacts
      preferentially located on basal and apical oblique dendrites, was due to
      differences in transmitter release probability of the projecting neurones and, to
      a lesser extent, to differenc

PMID- 9147330
TI  - Disinhibition of rat hippocampal pyramidal cells by GABAergic afferents from the
      septum.
AB  - 1. Slices were prepared from rat forebrain to include both the septum and the
      hippocampus in order to examine the effects of septal stimulation on hippocampal
      inhibitory circuits. 2. Repetitive stimulation of septo-hippocampal fibres caused
      a maintained decrease in the frequency of spontaneous IPSPs recorded from CA3
      pyramidal cells in the presence of antagonists of excitatory amino acid receptors
      and of muscarine receptors. 3. In records made from pyramidal cells with CsCl
      filled electrodes, IPSPs were examined at potentials both more positive and more
      negative than their reversal potential. Single septal stimuli hyperpolarized
      pyramidal cells when IPSPs were depolarizing events and depolarized them when
      IPSPs were hyperpolarizing. The GABAA receptor antagonist picrotoxin abolished
      the effects of septal stimulation. 4. Activation of septal afferents initiated an
      IPSP in hippocampal inhibitory cells but not in pyramidal cells. Septal IPSPs had
      similar kinetics to those initiated by local hippocampal stimulation and could
      suppress inhibitory cell discharge. 5. In pyramidal cells recorded with potassium
      acetate-filled electrodes, septal stimuli initiated a depolarization that
      increased with the driving force for Cl- and that could cause firing. 6. Rhythmic
      stimulation of septo-hippocampal fibres at 5 Hz initiated, in the hippocampus, a
      maintained out-of-phase oscillation of pyramidal cell discharge and inhibitory
      cell firing, as detected by the occurrence of spontaneous IPSPs. 7. These results
      suggest that GABAergic septo-hippocampal afferents selectively inhibit
      hippocampal inhibitory cells and so disinhibit pyramidal cells. This
      disinhibition could contribute to the transmission of the theta rhythm from the
      septum to the hippocampus.

PMID- 9147329
TI  - Excitatory synaptic site heterogeneity during paired pulse plasticity in CA1
      pyramidal cells in rat hippocampus in vitro.
AB  - 1. The properties of individual excitatory synaptic sites onto adult CA1
      hippocampal neurons were investigated using paired pulse minimal stimulation and
      low noise whole-cell recordings. Non-NMDA receptor-mediated synaptic responses
      were isolated using a pharmacological blockade of NMDA and GABAA receptors.
      Amongst the twenty-five stationary ensembles there were twelve showing paired
      pulse potentiation, two showing paired pulse depression and eleven with no
      significant net change. The signal-to-noise ratio averaged 4.5:1. There was no
      correlation between the amplitude of the first and second responses after
      separation of failures: the percentage of failures averaged 33.6% for the
      conditioning pulse and 31.7% for the test pulse. 2. Site-directed Bayesian
      statistical analysis was developed to predict the likely number of activated
      synapses, synaptic response amplitudes, probability of release and intrinsic
      variation at each individual synaptic site. Extensive simulations showed the
      usefulness of this model and defined appropriate parameters. These simulations
      demonstrated only small errors in estimating parameters of data sets with a small
      number of sites (< 10) and similar characteristics to the physiological data
      sets. 3. Physiological ensembles showed between one and three synaptic sites,
      which exhibited a wide range of values for release probability (0.03-0.99),
      synaptic amplitudes (1.46-16.8 pA; approximately 62% coefficient of variation
      between sites) and intrinsic variation over time (approximately 36%). Paired
      pulse plasticity occurred primarily from alterations in the release probabilities
      but a few ensembles also showed small changes in site amplitude. Initial release
      probability correlated negatively with the degree of paired pulse potentiation.
      Whilst it was possible to use simple assumptions regarding site homogeneity (such
      as required for a binomial process) for 48% (12 out of 25) of the data sets, the
      Bayesian analysis was necessary to reveal the complex changes and heterogeneity
      that occurred in the other 52% of the data sets. The Bayesian site analysis
      robustly indicated the presence of considerable site heterogeneity, significant
      intrinsic site variation over time and changes in parameters at individual
      synaptic sites with plasticity.

PMID- 9147331
TI  - Modulation of GABAA receptor-mediated IPSCs by neuroactive steroids in a rat
      hypothalamo-hypophyseal coculture model.
AB  - 1. We have used the whole-cell configuration of the patch-clamp technique to
      investigate the effects of neuroactive steroids on GABAA receptor-mediated
      synaptic transmission between rat hypothalamic neurones and pituitary
      intermediate lobe (IL) cells grown in coculture. In order to discriminate between
      possible pre- and postsynaptic sites of action, the effects of neurosteroids on
      GABAA receptor-mediated synaptic currents (IPSCs) were compared with those of
      GABAA currents (IGABA) triggered by local application of 50 or 500 microM GABA,
      which yielded approximately half-maximal and maximal responses, respectively. 2.
      In primary cultures of rat pituitary IL cells, allopregnanolone (5 alpha-pregnan
      3 alpha-ol-20-one) reversibly potentiated IGABA in a dose-dependent manner with a
      threshold between 0.1 and 1 nM. At a concentration of 10 nM, allopregnanolone
      increased the response evoked by 50 microM GABA by +21.4 +/- 5.1% (n = 8), but
      had no effect on IGABA induced by 500 microM GABA. The beta-isomer of
      allopregnanolone, epipregnanolone (5 beta-pregnan-3 beta-ol-20-one, 10 nM), had
      no effect on IGABA at any concentration of GABA tested. 3. At concentrations
      lower than 10 microM, pregnenolone sulphate (5-pregnen-3 alpha-ol-20-one
      sulphate) did not significantly inhibit IGABA. However, at 10 microM, a
      systematic reduction of IGABA evoked by 50 and 500 microM GABA was observed, with
      mean values of -80 and -60%, respectively. This blocking effect was reversible
      and accompanied by a marked acceleration of decay of GABAA currents during the
      application of GABA. 4. In isolated pairs of synaptically connected hypothalamic
      neurones and IL cells, allopregnanolone (10 nM) augmented the mean amplitude of
      spontaneous IPSCs (sIPSCs) and electrically evoked IPSCs (eeIPSCs) by about 40%
      and increased the mean frequency of sIPSCs. Allopregnanolone (10 nM) also
      markedly increased the frequency of miniature IPSCs (mIPSCs) recorded in the
      presence of TTX (0.5 microM), but without modifying their mean amplitude.
      Epipregnanolone had no effect on the amplitude or frequency of sIPSCs. Neither
      epipregnanolone nor allopregnanolone modified the time to peak and decay time
      constants of GABAergic IPSCs. 5. Pentobarbitone (50 microM), a positive
      allosteric modulator of GABAA receptors, did not affect the amplitude of sIPSCs
      or eeIPSCs, but significantly increased the decay time constants of both types of
      IPSCs. Pentobarbitone had no effect on the frequency of sIPSCs. 6. Pregnenolone
      sulphate (10 microM) completely and reversibly blocked sIPSCs and eeIPSCs.
      Progressive block of IPSCs was correlated with a gradual decrease of the mean
      decay time constant. 7. Our results suggest that, under physiological conditions,
      allopregnanolone might be a potent modulator of GABAergic synaptic transmission,
      acting at both pre- and postsynaptic sites. The involvement of pregnenolone
      sulphate as a modulator of GABAergic IPSCs under physiological conditions is,
      however, more questionable. The mechanisms of action of both types of
      neurosteroids are discussed.

PMID- 9147332
TI  - G-protein-mediated desensitization of metabotropic glutamatergic and muscarinic
      responses in CA3 cells in rat hippocampus.
AB  - 1. Desensitization of a metabotropic response was investigated in CA3 pyramidal
      neurons in hippocampal slice cultures using the patch-clamp technique. 2. 1S,3R-1
      aminocyclopentane-1,3-dicarboxylate (1S,3R-ACPD), an agonist at metabotropic
      glutamate receptors (mGluRs), and metacholine (MCh), an agonist at muscarinic
      receptors, induced a cationic current that appears to be activated through a G
      protein-independent transduction process, as previously shown. Prolonged or
      repetitive bath application of agonists led to rapid desensitization of the
      cationic current with a time constant of approximately 20 s. 3. Complete recovery
      from desensitization was observed within 6 min. 4. These responses mediated by
      mGluRs and muscarinic receptors cross-desensitized. 5. Preventing the activation
      of G-proteins by loading cells with GDP beta S strongly reduced or suppressed
      desensitization, and resulted in a sustained inward cationic current. When cells
      were filled with GTP gamma S to irreversibly activate G-proteins, the
      desensitization process was enhanced such that a first application of agonist
      caused a markedly reduced response. 6. These results show that a cationic current
      induced by metabotropic agonists in hippocampal pyramidal cells undergoes
      apparent desensitization and suggests that this process occurs through a G
      protein-mediated inhibition of the underlying membrane conductance.

PMID- 9147333
TI  - Sustained outward rectification of oxytocinergic neurones in the rat supraoptic
      nucleus: ionic dependence and pharmacology.
AB  - 1. Intracellular recordings were obtained in vitro from oxytocin and vasopressin
      neurones from dioestrous and lactating female rats. Oxytocin neurones were
      characterized under current clamp by the expression of a depolarization
      activated, sustained outward rectification (SOR) and a rebound depolarization
      (RD). 2. An increment in extracellular K+ shifted the expression of the SOR and
      RD towards a more depolarized membrane potential, indicating that the mechanisms
      underlying these events are dependent on extracellular potassium. 3. The SOR and
      RD were blocked by external tetraethylammonium (10 mM) and Ba2+ (0.1-0.5 mM). Cs+
      (2 mM) blocked the hyperpolarization-activated inward rectification without
      affecting the expression of the SOR and RD. 4. The SOR was not affected by 4
      aminopyridine (6 mM). However, the rebound amplitude was significantly enhanced,
      indicating that the activation of a transient outward current interacts with the
      expression of the rebound. 5. Iberiotoxin (100 nM) and apamin (50 nM), toxins
      known to block some calcium-dependent potassium conductances, did not affect the
      expression of the SOR and RD. 6. The SOR and RD were significantly reduced by
      Cd2+ (0.5 mM) but not by Ni2+ (0.25 mM). 7. Muscarine (10 microM) did not affect
      the SOR or the RD. 8. These results indicate that the SOR and RD depend upon a
      depolarization-activated, sustained outward potassium current, which might be
      calcium dependent. A current with these characteristics has never been described
      before in the magnocellular system. Voltage-clamp experiments are needed to
      completely characterize this potassium conductance selectively expressed by
      oxytocin neurones.

PMID- 9147334
TI  - Dissociations between behavioural recovery and restoration of vestibular activity
      in the unilabyrinthectomized guinea-pig.
AB  - 1. In the guinea-pig, a unilateral labyrinthectomy induces postural disturbances
      and an ocular nystagmus which abate or disappear over time. These behavioural
      changes are accompanied by an initial collapse and a subsequent restoration of
      the spontaneous activity in the neurones of the ipsilateral vestibular nuclei.
      Recently, it has been shown that the vestibular neuronal activity remained
      collapsed over at least 10 h whereas its restoration was complete 1 week after
      the lesion. The aims of this study were to determine when restoration of
      spontaneous activity in the partially deafferented vestibular neurones started
      and to compare the time courses of the behavioural and neuronal recoveries in
      guinea-pigs that had undergone a unilateral labyrinthectomy. 2. Neuronal
      discharge measurements were made using chronic extracellular recording of single
      unit activity. After a left labyrinthectomy, electrodes, were placed on the site
      of the destroyed labyrinth to enable stimulation of the left vestibular nerve.
      Behavioural measurements included chronic recording of eye movements by the
      scleral search coli technique. After a left labyrinthectomy, lateral deviation of
      the head, twisting of the head, and eye velocity of the slow phases of the
      nystagmus were measured. 3. The neuronal activity of the rostral part of the
      vestibular nuclear complex on the lesioned side was recorded in alert guinea-pigs
      over 4 h recording sessions between 12 and 72 h after the lesion. 4. The
      criterion used to select vestibular neurones for analysis was their recruitment
      by an electric shock on the vestibular nerve. In addition, in order to explore a
      uniform population, we focused on neurones recruited at monosynaptic latencies
      (0.85-1.15 ms). 5. For each recording period, the mean resting rate was
      calculated animal by animal and the grand mean of these individual resting rate
      means was calculated. Previously, a decline in the grand mean resting rate from
      35.8 +/- 6.0 spikes s-1 (control state) to 7.1 +/- 4.2 spikes s-1 during the
      first 4 h after labyrinthectomy has been shown. In the present study, the first
      sign of recovery was observed during the 12-16 h recording period when the
      resting rate grand mean increased to 16.3 +/- 3.9 spikes s-1. This grand mean
      activity did not change significantly during the following 12 h. Thereafter,
      restoration of neuronal activity improved and was complete 1 week after the
      lesion. 6. Although the abatement of the vestibular symptoms roughly paralleled
      the restoration of neuronal activity in the vestibular nuclei, some discrepancies
      between the time courses of both phenomena emerged. An important step in postural
      recovery (the animals managed to stand up) and a major part of the abatement of
      the nystagmus occurred before the recovery of vestibular neuronal activity. In
      addition, lateral deviation of the head disappeared while restoration of the
      neuronal activity was incomplete, but significant head twisting was still evident
      when vestibular resting rates had recovered completely. 7. We conclude that
      restoration of neuronal activity in the ipsilateral vestibular nuclei starts 12 h
      after the lesion and that restoration of neuronal activity in the ipsilateral
      vestibular nuclei is not the only mechanism underlying behavioural vestibular
      compensation.

PMID- 9147335
TI  - Sarcomere dynamics and contraction-induced injury to maximally activated single
      muscle fibres from soleus muscles of rats.
AB  - 1. The focal nature of contraction-induced injury to skeletal muscle fibres may
      arise from heterogeneities in sarcomere length that develop during contractions.
      We tested the hypothesis that when a maximally activated single permeabilized
      fibre segment is stretched and a deficit in maximum isometric force (force
      deficit) is produced, the regions of sarcomeres with the longest lengths of prior
      to the stretch contain the majority of the damaged sarcomeres when the fibre is
      returned to optimum length (Lo) after the stretch. 2. Single fibre segments (n =
      16) were obtained from soleus muscles of rats. Average sarcomere length at five
      discrete positions along the length of each fibre was determined by lateral
      deflection of a diode laser spot. Diffraction patterns were obtained while fibres
      were relaxed and immediately before, during and after a single stretch of 40%
      strain relative to Lo. Following the stretch, the regions of each fibre that
      potentially contained damaged sarcomeres were identified by an increased scatter
      of the first-order diffraction patterns. The damage was confirmed by light and
      electron microscopy. 3. While single fibre segments were in relaxing solution,
      the mean value for all of the average sarcomere lengths sampled (n = 80) was 2.53
      +/- 0.01 microns (range, 2.40-2.68 microns). During the maximum isometric
      contraction before each stretch, the mean sarcomere length decreased to 2.42 +/-
      0.02 microns and the range increased to 2.12-3.01 microns. 4. During the stretch
      of 40% strain, all regions of sarcomeres were stretched onto the descending limb
      of the length-force curve, but sarcomere lengthening was non-uniform. After the
      stretch, when the maximally activated fibres were returned to Lo, the force
      deficit was 10 +/- 1%. Microscopic evaluation confirmed that the regions with the
      longest sarcomere lengths before the stretch contained the majority of the
      damaged sarcomeres after the stretch. We conclude that when heterogeneities in
      sarcomere length develop in single permeabilized fibre segments during a maximum
      isometric contraction, the sarcomeres in the regions with the longest lengths are
      the most susceptible to contraction-induced injury.

PMID- 9147336
TI  - Active and passive forces of isolated myofibrils from cardiac and fast skeletal
      muscle of the frog.
AB  - 1. Force measurements in isolated myofibrils (15 degrees C; sarcomere length,
      2.10 microns) were used in this study to determine whether sarcomeric proteins
      are responsible for the large differences in the amounts of active and passive
      tension of cardiac versus skeletal muscle. Single myofibrils and bundles of two
      to four myofibrils were prepared from glycerinated tibialis anterior and
      sartorius muscles of the frog. Skinned frog atrial myocytes were used as a model
      for cardiac myofibrils. 2. Electron microscope analysis of the preparations
      showed that: (i) frog atrial myocytes contained a small and variable number of
      individual myofibrils (from 1 to 7); (ii) the mean cross-sectional area and mean
      number of myosin filaments of individual cardiac myofibrils did not differ
      significantly from those of single skeletal myofibrils; and (iii) the total
      myofibril cross-sectional area of atrial myocytes was on average comparable to
      that of bundles of two to four skeletal myofibrils. 3. In maximally activated
      skeletal preparations, values of active force ranged from 0.45 +/- 0.03 microN
      for the single myofibrils (mean +/- S.E.M.; n = 16) to 1.44 +/- 0.24 microN for
      the bundles of two to four myofibrils (n = 9). Maximum active force values of
      forty-five cardiac myocytes averaged 1.47 +/- 0.10 microN and exhibited a non
      continuous distribution with peaks at intervals of about 0.5 microN. The results
      suggest that variation in active force among cardiac preparations mainly reflects
      variability in the number of myofibrils inside the myocytes and that individual
      cardiac myofibrils develop the same average amount of force as single skeletal
      myofibrils. 4. The mean sarcomere length-resting force relation of atrial
      myocytes could be superimposed on that of bundles of two to four skeletal
      myofibrils. This suggests that, for any given amount of strain, individual
      cardiac and skeletal sarcomeres bear essentially the same passive force. 5. The
      length-passive tension data of all preparations could be fitted by an exponential
      equation. Equation parameters obtained for both types of myofibrils were in
      reasonable agreement with those reported for larger preparations of frog skeletal
      muscle but were very different from those estimated for multicellular frog atrial
      preparations. It is concluded that myofibrils are the major determinant of
      resting tension in skeletal muscle; structures other than the myofibrils are
      responsible for the high passive stiffness of frog cardiac muscle.

PMID- 9147337
TI  - The Digital Anatomist distributed framework and its applications to knowledge
      based medical imaging.
AB  - The domain of medical imaging is anatomy. Therefore, anatomic knowledge should be
      a rational basis for organizing and analyzing images. The goals of the Digital
      Anatomist Program at the University of Washington include the development of an
      anatomically based software framework for organizing, analyzing, visualizing and
      utilizing biomedical information. The framework is based on representations for
      both spatial and symbolic anatomic knowledge, and is being implemented in a
      distributed architecture in which multiple client programs on the Internet are
      used to update and access an expanding set of anatomical information resources.
      The development of this framework is driven by several practical applications,
      including symbolic anatomic reasoning, knowledge based image segmentation,
      anatomy information retrieval, and functional brain mapping. Since each of these
      areas involves many difficult image processing issues, our research strategy is
      an evolutionary one, in which applications are developed somewhat independently,
      and partial solutions are integrated in a piecemeal fashion, using the network as
      the substrate. This approach assumes that networks of interacting components can
      synergistically work together to solve problems larger than either could solve on
      its own. Each of the individual projects is described, along with evaluations
      that show that the individual components are solving the problems they were
      designed for, and are beginning to interact with each other in a synergistic
      manner. We argue that this synergy will increase, not only within our own group,
      but also among groups as the Internet matures, and that an anatomic knowledge
      base will be a useful means for fostering these interactions.

PMID- 9147338
TI  - Medical image databases: a content-based retrieval approach.
AB  - Information contained in medical images differs considerably from that residing
      in alphanumeric format. The difference can be attributed to four characteristics:
      (1) the semantics of medical knowledge extractable from images is imprecise; (2)
      image information contains form and spatial data, which are not expressible in
      conventional language; (3) a large part of image information is geometric; (4)
      diagnostic inferences derived from images rest on an incomplete, continuously
      evolving model of normality. This paper explores the differentiating
      characteristics of text versus images and their impact on design of a medical
      image database intended to allow content-based indexing and retrieval. One
      strategy for implementing medical image databases is presented, which employs
      object-oriented iconic queries, semantics by association with prototypes, and a
      generic schema.

PMID- 9147339
TI  - Understanding and using DICOM, the data interchange standard for biomedical
      imaging.
AB  - The Digital Imaging and Communications in Medicine (DICOM) Standard specifies a
      non-proprietary data interchange protocol, digital image format, and file
      structure for biomedical images and image-related information. The fundamental
      concepts of the DICOM message protocol, services, and information objects are
      reviewed as background for a detailed discussion of the functionality of DICOM;
      the innovations and limitations of the Standard; and the impact of various DICOM
      features on information system users. DICOM addresses five general application
      areas: (1) network image management, (2) network image interpretation management,
      (3) network print management, (4) imaging procedure management, (5) off-line
      storage media management. DICOM is a complete specification of the elements
      required to achieve a practical level of automatic interoperability between
      biomedical imaging computer systems--from application layer to bit-stream
      encoding. The Standard is being extended and expanded in modular fashion to
      support new applications and incorporate new technology. An interface to other
      Information Systems provides for shared management of patient, procedure, and
      results information related to images. A Conformance Statement template enables a
      knowledgeable user to determine if interoperability between two implementations
      is possible. Knowledge of DICOM's benefits and realistic understanding of its
      limitations enable one to use the Standard effectively as the basis for a long
      term implementation strategy for image management and communications systems.

PMID- 9147340
TI  - The barriers to electronic medical record systems and how to overcome them.
AB  - Institutions all want electronic medical record (EMR) systems. They want them to
      solve their record movement problems, to improve the quality and coherence of the
      care process, to automate guidelines and care pathways to assist clinical
      research, outcomes management, and process improvement. EMRs are very difficult
      to construct because the existing electronic data sources, e.g., laboratory
      systems, pharmacy systems, and physician dictation systems, reside on many
      isolated islands with differing structures, differing levels of granularity, and
      different code systems. To accelerate EMR deployment we need to focus on the
      interfaces instead of the EMR system. We have the interface solutions in the form
      of standards: IP, HL7/ASTM, DICOM, LOINC, SNOMED, and others developed by the
      medical informatics community. We just have to embrace them. One remaining
      problem is the efficient capture of physician information in a coded form.
      Research is still needed to solve this last problem.

PMID- 9147341
TI  - Nursing classification systems: necessary but not sufficient for representing
      "what nurses do" for inclusion in computer-based patient record systems.
AB  - Our premise is that from the perspective of maximum flexibility of data usage by
      computer-based record (CPR) systems, existing nursing classification systems are
      necessary, but not sufficient, for representing important aspects of "what nurses
      do." In particular, we have focused our attention on those classification systems
      that represent nurses' clinical activities through the abstraction of activities
      into categories of nursing interventions. In this theoretical paper, we argue
      that taxonomic, combinatorial vocabularies capable of coding atomic-level nursing
      activities are required to effectively capture in a reproducible and reversible
      manner the clinical decisions and actions of nurses, and that, without such
      vocabularies and associated grammars, potentially important clinical process data
      is lost during the encoding process. Existing nursing intervention classification
      systems do not fulfill these criteria. As background to our argument, we first
      present an overview of the content, methods, and evaluation criteria used in
      previous studies whose focus has been to evaluate the effectiveness of existing
      coding and classification systems. Next, using the Ingenerf typology of taxonomic
      vocabularies, we categorize the formal type and structure of three existing
      nursing intervention classification system--Nursing Interventions Classification,
      Omaha System, and Home Health Care Classification. Third, we use records from
      home care patients to show examples of lossy data transformation, the loss of
      potentially significant atomic data, resulting from encoding using each of the
      three systems. Last, we provide an example of the application of a formal
      representation methodology (conceptual graphs) which we believe could be used as
      a model to build the required combinatorial, taxonomic vocabulary for
      representing nursing interventions.

PMID- 9147342
TI  - Use of commercial record linkage software and vital statistics to identify
      patient deaths.
AB  - We evaluate the ability of a microcomputer program (Automatch) to link patient
      records in our hospital's database (N = 253,836) with mortality files from
      California (N = 1,312,779) and the U.S. Social Security Administration (N =
      13,341,581). We linked 96.5% of 3,448 in-hospital deaths, 99.3% for patients with
      social security numbers. None of 14,073 patients known to be alive (because they
      were subsequently admitted) was linked with California deaths, and only 6 (0.1%)
      of 6,444 were falsely identified as dead in the United States file. For patients
      with unknown vital status but items in the database likely to be associated with
      high 3-year mortality rates, we identified death records of 88% of 494 patients
      with cancer metastatic to the liver, 84% of 164 patients with pancreatic cancer,
      and 91% of 126 patients with CD4 counts of less than 50. Hospital data can be
      accurately linked with state and national vital statistics using commercial
      record linkage software.

PMID- 9147343
TI  - Phase II evaluation of clinical coding schemes: completeness, taxonomy, mapping,
      definitions, and clarity. CPRI Work Group on Codes and Structures.
AB  - OBJECTIVE: To compare three potential sources of controlled clinical terminology
      (READ codes version 3.1, SNOMED International, and Unified Medical Language
      System (UMLS) version 1.6) relative to attributes of completeness, clinical
      taxonomy, administrative mapping, term definitions and clarity (duplicate coding
      rate). METHODS: The authors assembled 1929 source concept records from a variety
      of clinical information taken from four medical centers across the United States.
      The source data included medical as well as ample nursing terminology. The source
      records were coded in each scheme by an investigator and checked by the coding
      scheme owner. The codings were then scored by an independent panel of clinicians
      for acceptability. Codes were checked for definitions provided with the scheme.
      Codes for a random sample of source records were analyzed by an investigator for
      "parent" and "child" codes within the scheme. Parent and child pairs were scored
      by an independent panel of medical informatics specialists for clinical
      acceptability. Administrative and billing code mapping from the published scheme
      were reviewed for all coded records and analyzed by independent reviewers for
      accuracy. The investigator for each scheme exhaustively searched a sample of
      coded records for duplications. RESULTS: SNOMED was judged to be significantly
      more complete in coding the source material than the other schemes (SNOMED* 70%;
      READ 57%; UMLS 50%; *p < .00001). SNOMED also had a richer clinical taxonomy
      judged by the number of acceptable first-degree relatives per coded concept
      (SNOMED* 4.56, UMLS 3.17; READ 2.14, *p < .005). Only the UMLS provided any
      definitions; these were found for 49% of records which had a coding assignment.
      READ and UMLS had better administrative mappings (composite score: READ* 40.6%;
      UMLS* 36.1%; SNOMED 20.7%, *p < .00001), and SNOMED had substantially more
      duplications of coding assignments (duplication rate: READ 0%; UMLS 4.2%; SNOMED*
      13.9%, *p < .004) associated with a loss of clarity. CONCLUSION: No major
      terminology source can lay claim to being the ideal resource for a computer-based
      patient record. However, based upon this analysis of releases for April 1995,
      SNOMED International is considerably more complete, has a compositional nature
      and a richer taxonomy. Is suffers from less clarity, resulting from a lack of
      syntax and evolutionary changes in its coding scheme. READ has greater clarity
      and better mapping to administrative schemes (ICD-10 and OPCS-4), is rapidly
      changing and is less complete. UMLS is a rich lexical resource, with mappings to
      many source vocabularies. It provides definitions for many of its terms. However,
      due to the varying granularities and purposes of its source schemes, it has
      limitations for representation of clinical concepts within a computer-based
      patient record.

PMID- 9147344
TI  - Medical imaging informatics: challenges of definition and integration.

PMID- 9147345
TI  - Call for a standard clinical vocabulary.

PMID- 9147346
TI  - Computer-based diagnostic support systems.

PMID- 9147347
TI  - The neurobiology of gonadal hormones and cognitive decline in late life.

PMID- 9147348
TI  - Risk factors of early menopause in two generations of gainfully employed French
      women.
AB  - OBJECTIVES: Numerous studies have been focused on the detection of factors which
      can act on the age of menopause. Little is known about the factors related to the
      occurrence of an early menopause. Some factors such as occupational work factors
      and generational effects have not been taken into account as yet. METHODS: We
      examined the risk factors of early natural menopause (before age 45) in a large
      random sample of gainfully employed French women born in the years 1938 (n =
      1743) and 1943 (n = 1959). The subjects were selected from files of an
      occupational physician. A woman was considered to be post-menopausal when at
      least 12 consecutive months had passed without menstruation at the time of the
      survey. Subjects were questioned and examined during their annual visit by the
      occupational physician. Occupational history, working conditions, living
      conditions, smoking habits and reproductive history were explored. RESULTS: The
      prevalence of early natural menopause, before age 45, was higher in the
      generation of 1938 (5.3%) than in that of 1943 (3.3%) with P < 0.01. After
      multivariate regressions, significant relationships existed statistically between
      the occurrence of early natural menopause and marital status, educational level,
      age at first childbirth and breast-feeding of children. CONCLUSIONS: Our results
      show important generation effects. There was no evidence of a significant
      relationship between early natural menopause at 45 years of age and factors
      relative to heavy physical work conditions.

PMID- 9147349
TI  - Gender differences in sexual activity among mid-aged adults in Massachusetts.
AB  - OBJECTIVES: The purpose of this study was to determine if self-reported measures
      of sexual activity differ between aging men and women. METHODS: Responses to 12
      questions concerning various aspects of sexual activity were compared between 349
      women and 589 men aged 51-61, who were participants in two larger community
      surveys in Massachusetts conducted in 1987 and 1988. Comparisons were made by
      least squares means adjusted for age, socio-demographic and health-related
      variables. Analyses were stratified by the presence or absence of one or more
      current sexual partners. RESULTS: Regardless of partner status, overall
      satisfaction with sex life did not differ between men and women. For those with
      partners, the mean frequency of intercourse was somewhat higher for women than
      men, while mean frequency of sexual desire and fantasies was significantly higher
      for men. Similar results were seen for those without partners, although frequency
      was lower and did not differ by gender. CONCLUSIONS: We found no gender
      difference in sexual satisfaction and little difference in frequency in mid-aged
      adults, but sexual desire and fantasies were more common for men.

PMID- 9147350
TI  - Estimating the cost per avoided hip fracture by osteoporosis treatment in Italy.
AB  - OBJECTIVES: A cost-effectiveness analysis on osteoporosis treatment has been
      carried out as the basis for an estimate of the cost per avoided hip fracture
      (CPAHF) in Italy. METHODS: We have assumed as correct, reported data on the
      efficacy of calcitonin in preventing hip fractures in European women over 50
      (Mediterranean Osteoporosis Study). Health-care costs were calculated using
      Weinstein and Stason's equation. RESULTS: Given the incidence of such fractures
      in Italy and their cost to the health service, we calculate that in order to
      prevent one hip fracture 1285 women need to be treated with calcitonin at a cost
      of over two million dollars. The introduction of an element of screening (bone
      mass measurement to select a high risk subpopulation) would reduce the CPAHF by
      65%. Choice of a more effective treatment (as the hormone replacement therapy)
      would be cost-neutral. CONCLUSIONS: Drug-related costs, selection of high risk
      subpopulations and drug efficacy have important implications in the estimation of
      optimal CPAHF.

PMID- 9147351
TI  - Hypolactasia and metabolic changes in post-menopausal women.
AB  - OBJECTIVES: The aims of the study were to evaluate the prevalence of hypolactasia
      in a group of post-menopausal women in Southern Italy, and to relate hypolactasia
      to possible changes occurring in biochemical indicators of carbohydrate and fat
      metabolism as well as in biochemical markers of bone metabolism. METHODS: Fifty
      post-menopausal women entered the study. Lactose malabsorbers were identified by
      breath hydrogen test. The kinetics of D-xylose was evaluated by a graphic
      mathematical analysis after oral administration of a solution of 10 g of D-xylose
      in water. Serum glucose, insulin, C-peptide, cholesterol and triglycerides were
      assayed by commercial kits. The evaluation of dietary habits and physical
      activities was performed by a questionnaire. The assessment of bone turnover was
      obtained by measuring osteocalcin, serum alkaline phosphatase, calcium,
      phosphorus, and urinary hydroxyproline and urinary calcium expressed as a ratio
      or urinary creatinine. RESULTS: Twenty-six of 50 women showed hypolactasia.
      Significant differences were found in serum levels of insulin, glucose, and
      triglycerides, which were lower in malabsorbers than lactose absorbers, and in
      HDL-cholesterol levels which were higher in the first group than in the second.
      As regards bone turnover, dietary habits or lactose intake, there were no
      significant differences between the two groups. CONCLUSIONS: The significant
      differences found in serum levels of glucose, triglycerides, and HDL-cholesterol
      between lactose absorbers and malabsorbers may be imputable to the low or absent
      lactase activity which does not allow the whole amount of lactose in the small
      bowel of malabsorbers to be metabolized. Moreover, changes in lactose absorbing
      capacity of intestinal mucosa did not modify the intake of milk or its by
      products in malabsorbers as demonstrated by the analysis of food.

PMID- 9147352
TI  - Transvaginal color Doppler and CA125 as tools in the differential diagnosis of
      postmenopausal ovarian masses.
AB  - OBJECTIVE: To evaluate whether transvaginal color Doppler and CA125 are valid in
      differentiating malignant from benign postmenopausal ovarian masses. METHODS:
      Sixty-two women with ovarian masses were studied with transvaginal color Doppler
      ultrasound before surgery. Serum CA125 levels were also measured. Resistance
      index (RI) and pulsatility index (PI) were calculated from the waveforms
      generated from blood flow within the ovary. RESULTS: Benign tumors had a
      significantly higher pulsatility index (mean 1.23 +/- 1.02; range 0.65-2.99) and
      resistive index (mean 0.78 +/- 0.22; range 0.5-1.1) than did malignant tumors.
      However some overlap in individual values for benign and malignant lesions was
      found. RI and PI sensitivity were significantly higher than those with CA125 (P <
      0.05). Blood flow was detectable by color Doppler imaging in 95% of cases with
      malignant masses. CONCLUSION: Doppler sonographic evaluation of resistance and
      pulsatility indexes in the vessels of ovarian masses together with CA125
      increased the sensitivity of prediction of malignancy for pelvic masses, but
      further work is needed before the validity of these factors is proved.

PMID- 9147353
TI  - Percutaneous estradiol gel with an intrauterine levonorgestrel releasing device
      or natural progesterone in hormone replacement therapy.
AB  - OBJECTIVE: To evaluate the bleeding patterns and clinical compliance associated
      with postmenopausal amenorrhea-inducing forms of hormone replacement therapy
      using either percutaneous estradiol-gel and a levonorgestrel-releasing
      intrauterine device or an oral/vaginal natural progesterone. METHODS: Sixty
      postmenopausal women with an intact uterus were followed over 12 months in this
      open, non-randomised, parallel group study. All patients continuously received a
      gel containing 1.5 mg of estradiol daily. The women were divided into three
      groups on the basis of progestin administration. Twenty women (group I) had a
      levonorgestrel-releasing device (LNG-IUD) inserted at the beginning of the study.
      Twenty-one women (group II) received oral natural micronised progesterone (oral
      P) 100 mg daily during 25 calendar days each month, and 19 women (group III) used
      vaginal natural micronised progesterone (vaginal P) 100-200 mg daily during 25
      calendar days each month (higher dose if spotting occurred). Clinic visits were
      at 0, 3, 6 and 12 months. Bleeding patterns were recorded by the patient in a
      diary and clinical compliance was evaluated at control visits during the
      treatment. Symptoms were recorded using a modified Kuppermann index. The serum
      estradiol concentration was determined at the 0, 6 and 12 month control visits.
      RESULTS: 80% (n = 16) of the patients in the LNG-IUD group, 67% (n = 14) in the
      oral P group II and 53% (n = 10) in the vaginal P group were without bleeding at
      12 months. Spotting was common during the first 3 months. Symptom relief was good
      in each group. The LNG-IUD did not cause any serious side-effects. Compliance was
      good for LNG-IUD and oral progesterone but not for vaginal progesterone.
      CONCLUSIONS: Percutaneous estradiol-gel associated with LNG-IUD is an appropriate
      method of hormone replacement therapy. The combination of oral natural
      progesterone with estradiol-gel is also useful, although bleeding episodes
      complicated the treatment in one third of the patients. The vaginal
      administration of natural progesterone was impractical due to bleeding disorders.

PMID- 9147354
TI  - Endometrial histology and bleeding patterns in post-menopausal women taking
      sequential, combined estradiol and dydrogesterone.
AB  - OBJECTIVES: To determine the endometrial response and bleeding patterns in post
      menopausal women who were given a sequential hormone replacement regimen with
      estradiol 2 mg and dydrogesterone 10 mg. METHODS: One-hundred-and-eighty-eight
      (188) post-menopausal women with amenorrhea of 6 months or longer, with
      FSH/estradiol (E2) levels in the post-menopausal range and normal endometrium
      were entered in the study. All patients received a daily dose of 2 mg E2 during
      day 1-14 of each 28 day cycle and 2 mg E2 combined with 10 mg dydrogesterone
      during cycle day 15-28. The total duration of treatment was 12 months (13 cycles
      of 28 days). RESULTS: The rate of adequate progestational response (secretory or
      atrophic) in the 146 patients who remained in the study for at least 356 days
      with 90% study medication compliance and received an endometrial biopsy after 13
      cycles of study medication was 97.2%. Three patients had proliferative
      endometrium and one simple hyperplasia. Cyclic bleedings in the 153 women who
      remained on study medication for at least 76 days occurred in over 85% of all
      cycles; the day of onset occurring regularly on day 13 or 14 of the combined
      period; the mean duration of bleeding per cycle was approximately 5 days with
      most patients having (very) slight bleeding. Sixty percent of patients had no
      intermittent bleedings over the whole 12-month study period. The average
      incidence of intermittent bleeding in the remaining patients was only 2.7 and
      generally of very slight quantities and of short duration. Per evaluable cycle
      the percentage of patients with an intermittent bleeding varies from 4.6 to 9.8%.
      Only two patients discontinued therapy because of bleeding problems. A clear
      decrease in the incidence of typical menopausal symptoms, i.e. hot flushes and
      night sweats was observed by the first visit after 6 weeks of treatment.
      CONCLUSIONS: The endometrial safety of 2 mg E2 sequentially combined with 10 mg
      dydrogesterone is very good as determined by the histologic response of the
      endometrium. The incidence of cyclic bleedings with this combination therapy is
      very high as is the regularity of day of onset and duration of bleeding. Blood
      loss during intermittent bleedings was mild and of short duration.

PMID- 9147355
TI  - Th1/Th2 changes in aging.

PMID- 9147356
TI  - Evidence of enhanced type 2 immune response and impaired upregulation of a type 1
      response in frail elderly nursing home residents.
AB  - Peripheral blood mononuclear cells (PBMC) of frail elderly nursing home residents
      had significantly higher PHA-induced interleukin-10 (IL-10) production compared
      to PBMC's from young control subjects. No correlation was observed between IL-10
      production and interleukin-12 (IL-12) p40 production, proliferative response or
      with the proportion of CD28-negative T cells. To better characterize the host
      response to a ubiquitous pathogen, the dose response and time-dependent (kinetic)
      production of IL-10 and IL-12 p40 of PBMC stimulated with Staphylococcus aureus
      Cowan (SAC) was studied. IL-10 production continued to increase at 48 h, while IL
      12 p40 levels declined or remained stable, in both young and elderly subjects. In
      analyzing how excessive IL-10 production might influence antigen presenting cell
      functions, IL-12 was markedly inhibited by recombinant IL-10 (rIL-10), while anti
      IL-10 enhances IL-12 p40 production in cultures from young controls; but the PBMC
      cultured from an elderly cohort were not able to generate similar absolute levels
      of IL-12 p40 even in the presence of anti-IL-10. These preliminary data suggest
      that there may be both over production of IL-10 in some individuals, as well an
      an impaired ability to upregulate a T Helper 1 (type 1) reaction. These age
      related changes could even be more dramatic at the tissue level and contribute to
      the impaired delayed type hypersensitivity (DTH) and failed host defense to
      infection, such as to primary and reactivation tuberculosis.

PMID- 9147357
TI  - Does the secretion of cytokines in the periphery reflect their role in bone
      metabolic diseases?
AB  - Much interest has been focused on the role of the immune system in bone
      remodeling. Here, we compare the production of Interleukin-1 beta (IL-1 beta) and
      interleukin-6 (IL-6) by peripheral blood mononuclear cells (PBMC) in elderly
      Paget's patients, elderly osteoporotic patients and in normal elderly subjects.
      We studied Paget's patients (71.00 +/- 3.74 years), 7 osteoporotic patients
      (71.86 +/- 3.23 years), age and sex matched, and 5 elderly healthy control
      subjects (74.20 +/- 4.10 years) An ELISA test was used to quantify IL-1 beta and
      IL-6 in the supernatant culture of PBMC stimulated by phytohemagglutinin (PHA).
      IL-1 beta and IL-6 production from Paget's patients (IL-1 beta, 651.43 +/- 95.92
      pg/ml; IL-6, 1402.85 +/- 148.11 pg/ml) was not statistically different from the
      production observed in the osteoporotic patients (IL-1 beta, 552.57 +/- 79.04
      pg/ml; IL-6, 1458.85 +/- 118.35 pg/ml) and in the healthy elderly group (IL-1
      beta, 717.60 +/- 131.34 pg/ml; IL-6, 1502.40 +/- 211.90 pg/ml). Although IL-1 and
      IL-6 can be involved in the bone remodeling process, we did not find any
      difference when we compared their production by PBMC in elderly normal, elderly
      osteoporotic and elderly Paget's patients.

PMID- 9147358
TI  - Cytokines and impaired CD8+ CTL activity among elderly persons and the enhancing
      effect of IL-12.
AB  - We have previously demonstrated that about 70% of elderly persons exhibit
      deficient cytotoxic T lymphocyte (CD8+ CTL) responses against influenza viruses
      when compared to young persons. Since IFN-gamma, a Th1 cytokine and IL-4, a Th2
      cytokine, stimulate and inhibit CD8+ CTL responses respectively, their role(s) in
      the age-related CTL deficiency was investigated. Lymphocytes from young adults
      (34 +/- 5 years old) and elderly subjects (71 +/- 1 years old) were stimulated in
      vitro with influenza A/H3N2, A/H1N1 or influenza B virus for 6-7 days. The CD8+
      CTL activity against virus-infected autologous target cells was significantly
      lower among the elderly than the young subjects (P < 0.01). Following stimulation
      with influenza virus, IL-4 production in both age groups was similar on day 3 but
      significantly higher among elderly persons on day 6 (P < 0.05). In contrast, T
      cells from the elderly produced significantly lower IFN-gamma than did those from
      young persons on both days (P < 0.05). Treatment of T cells from young and
      elderly adults with recombinant human IL-12, a pivotal cytokine that stimulates
      Th1 cytokines, resulted in enhancement of CD8+ CTL activity and IFN-gamma
      production in a dose dependent manner (P < 0.01). IL-12-dependent enhancement of
      CTL activity was not always abrogated by anti-IFN-gamma antibody treatment. These
      results suggest that deficient influenza virus-specific CTL activity among the
      elderly is attributable to a Th1 to Th2 cytokine production switch. Immunotherapy
      with IL-12 could represent a useful approach to correct the CD8+ CTL deficiency
      and cytokine imbalance among elderly humans.

PMID- 9147359
TI  - Characteristics and maintenance of CD8+ T-cell clones found in old mice.
AB  - Old mice, like old human beings, contain large clones of CD8+ T-cells. These
      cells grow poorly in tissue culture, therefore it is difficult to maintain the
      cells in vitro. The cells can be grown after transfer to sublethally irradiated
      mice. This technique will be useful in further studies on the properties of the
      cells. Based on observations from such transfer experiments, we conclude that:
      (1) expansion of the T-cell clones in recipients is dramatic but slow; (2) chance
      events caused by endogenous antigens or gene mutations rather than exogenous
      antigens may account for the expansion of these clones; and (3) the expanded T
      cell clones are benign and do not cause malignancies.

PMID- 9147360
TI  - The age-associated decline in immune function of healthy individuals is not
      related to changes in plasma concentrations of beta-carotene, retinol, alpha
      tocopherol or zinc.
AB  - The decline in the lymphoproliferative response to mitogenic stimuli shows marked
      heterogeneity in elderly individuals. Adequate nutriture is required for optimal
      immune function, yet nutritional status may be compromised in the elderly. To
      address whether this variation in the proliferative response of elderly
      individuals is related to their nutritional status, we studied 61 elderly (80.5
      +/- 5.7 year-old) and 27 young (27.3 +/- 3.8 year-old) individuals participating
      in an ongoing assessment of their immune response to influenza vaccine.
      Ambulatory elderly individuals were recruited from five different retirement
      communities and were in good health upon enrollment in the study. Thirty-three
      percent of young and 54% of elderly subjects reported consuming micronutrient
      supplements daily during the study. Plasma and peripheral blood mononuclear cells
      (PBMC) were isolated from fasting individuals twice, 4-6 weeks apart. At both
      times, proliferative responses to the mitogens phytohemagglutinin (PHA),
      concanavalin A (Con A), and pokeweed mitogen (PWM) were significantly lower (P <
      0.004) in the elderly compared to the young. However, at both times, elderly
      participants had plasma concentrations of beta-carotene, retinol, alpha
      tocopherol and zinc that were either significantly greater than, or equal to,
      those of young subjects. No significant correlations between plasma
      concentrations of beta-carotene, retinol, alpha-tocopherol and zinc and level of
      proliferative responses to each stimuli were observed in elderly individuals at
      either time. Thus, the heterogeneity in the proliferative response to mitogenic
      stimuli exhibited by a healthy elderly population cannot be attributed to
      differences in these nutritional parameters.

PMID- 9147361
TI  - Diminished activation of the MAP kinase pathway in CD3-stimulated T lymphocytes
      from old mice.
AB  - Stimulation of the ERK family of protein kinases ('extracellular signal regulated
      kinases', also known as MAP kinases) plays an important role in the activation of
      many cell types, including T lymphocytes. ERKs are activated when they are
      phosphorylated by an upstream activator, the dual-specific protein kinase MEK. To
      see if aging leads to an impairment of MEK activation in mouse T cells, we used a
      mobility shift assay in which activation of MEK leads to phosphorylation and
      altered mobility of ERK-2 kinase. Similarly, we monitored mobility of pp90rsk, a
      known ERK substrate, as an indication of ERK function. We found an age-related
      decline in the ability of mouse T cells to activate both MEK and ERK function in
      response to stimulation by antibodies to the CD3 chain of the T cell receptor.
      Aging did not alter the kinetics of enzyme activation, but did diminish (by about
      2-fold) the maximal level of substrate converted into the slower migrating form.
      Naive and memory CD4 T cells from young mice were equally able to convert ERK2 to
      its slower migrating form, suggesting that the decline in MEK function is not
      likely to be attributable to the shift, with age, from naive to memory T cell
      predominance. Our data suggest that age-dependent declines in gene activation,
      including genes for key cytokines like IL-2, may be due to declines in the
      upstream signals that lead to activation of the MEK/ERK protein kinase cascade.

PMID- 9147362
TI  - Thymosin alpha 1 antagonizes dexamethasone and CD3-induced apoptosis of CD4+ CD8+
      thymocytes through the activation of cAMP and protein kinase C dependent second
      messenger pathways.
AB  - It is well established that glucocorticoid hormones and anti-CD3 monoclonal
      antibodies induce apoptosis in immature developing thymocytes. This process can
      be modulated by soluble factors, anti-oxidants and adhesion receptors. Previously
      we have demonstrated that thymosin alpha 1 (T alpha 1), a 28-amino acid thymic
      peptide hormone, is a dose and time dependent antagonist of dexamethasone (DEX)
      and CD# induced DNA fragmentation of murine thymocytes in vitro. To further
      investigate the mechanism of T alpha 1 action we determined a T alpha 1 sensitive
      thymocyte population and examined some of the molecular events associated with T
      alpha 1 anti-apoptotic activity. Phenotypic analysis of the sub-populations of
      thymocytes, based on CD4 and CD8 expression, revealed that T alpha 1 exerts its
      effect on CD4+ CD8+ immature thymocytes. T alpha 1 treatment of thymocytes delays
      the production of free radicals and the subsequent consumption of glutathione,
      that is observed during both DEX and CD3 induced apoptosis. We further
      demonstrate that T alpha 1 stimulates the production of cAMP and activates PKC in
      thymocytes. These data suggest that T alpha 1 exerts an influence on the
      development of a population of immature T-cells in the thymus by effecting the
      sensitivity of thymocytes to apoptosis during the pre-selection stages of thymic
      development. Our studies also suggest that the mechanism of T alpha 1 action
      involves the induction of both cAMP and PKC dependent second messenger pathways.

PMID- 9147363
TI  - Thymocyte progenitors and T cell development in aging.
AB  - Dysfunction of T lymphocytes in aging has been causally related to a gradual loss
      of the thymic microenvironmental function. However, in view of the fact that T
      cells are generated from bone marrow-derived stem cells that settle in the
      thymus, we have investigated the possibility that aging effects on the bone
      marrow have an impact on T cell development. Our approach was based on seeding of
      bone marrow cells, from young and old mice, onto lymphoid-depleted fetal thymus
      explants, and examining the patterns of T lymphocyte development under organ
      culture conditions. The results indicate multifactorial effects of aging, on pre
      thymic and intra-thymic development processes, as well as on feedback regulation
      by mature T cells.

PMID- 9147364
TI  - Altered expression of various receptors on T cells in young and old mice after
      mitogenic stimulation: a flow cytometric analysis.
AB  - To understand mechanism underlying the age-related impairment of T cell
      functions, changes in the expression of cell surface receptors were examined in T
      cells after mitogenic stimulation by flow cytometry and results were compared
      between young and old mice. Before stimulation, no significant difference was
      observed in the density of TCR alpha beta, CD3, CD122 (IL-2R beta), IL-2R gamma,
      CD28 and CD95 (Fas) of T cells between young and old mice. As for CD25(IL-2R
      alpha) and CTLA-4, relative intensity and percentage of positive cells were
      higher in old than in young mice, although the levels were low compared with
      those after stimulation. After mitogenic stimulation, increased expression of the
      density was observed in CD25, IL-2R beta, IL-2R gamma, CD28, CTLA-4 and CD95 and
      the magnitude of increase was more pronounced in T cells from young than those
      from old mice. The expression of TCR alpha beta and CD3 decreased after mitogenic
      stimulation, and the degree of expression quickly recovered to the initial level
      in young mice, but not in old mice. Lower expression of TCR, IL-2 receptors and
      co-stimulatory molecules in T cells from old mice could be responsible for the
      impaired proliferation after mitogenic stimulation.

PMID- 9147365
TI  - Increased apoptosis of CD45RO- T cells with aging.
AB  - Increasing susceptibility to infectious and autoimmune phenomena have long been
      recognized to accompany advancing age in otherwise healthy individuals. Recently
      animal models of aging have suggested that age-associated immune dysfunction may
      correlate with defects in T cell apoptosis. We have examined activation-induced
      apoptosis defects in human peripheral T cells from young individuals (mean age =
      31 +/- 3 years old) compared to aged individuals (mean age = 67 +/- 8 years old).
      Following in vitro activation of T cells with PHA and IL-2, apoptosis was
      measured in T cell subsets using 7-amino actinomycin D (7-AAD) staining and
      analysis via three colour flow cytometry. There was no significant difference in
      apoptosis of the total CD3+ T cell population at early and late time points.
      Interestingly, increased apoptosis in the CD3+ CD45RO- T cell population of older
      adults was observed by culture day 6. While the total number of CD3+ CD45RO-
      cells was not different between young (< 33 years) and old (> 65 years)
      individuals, 32% of these cells did not undergo apoptosis in younger individuals
      while only 10% of these cells avoided this fate in older individuals. These
      results suggest that accumulation of CD45RO+ T cells may occur in aged subjects
      due in part to preferential elimination of CD45RO- cells with activation.
      Furthermore, as new or continued immune response requires differentiation of
      CD45RO+ T cells to CD45RO+ T cells after activation, increased apoptosis instead
      of survival in aged individuals could lead to observed T cell immune deficiency.

PMID- 9147366
TI  - Age-related changes in non-receptor dependent generation of reactive oxygen
      species from phagocytes of healthy adults.
AB  - Several authors have shown that neutrophil generation of reactive oxygen species
      (ROS) declines with advancing age. Similar changes have also been suggested in
      monocytes. In both cases alterations in second messenger activity have been
      implicated as the most likely explanation for these observations. The aim of this
      study was to investigate the effect of age on phagocyte ROS generation,
      stimulated by the direct activation of protein kinase C (PKC). Venous blood was
      drawn from normal healthy subjects, cells were separated on a double density
      gradient into mononuclear and polymorphonuclear (pmn) cells. Phorbol myristate
      acetate (PMA) was employed as a cell stimulus. Superoxide generation was measured
      by cytochrome c reduction and myeloperoxidase (MPO) products by measurement of
      peak luminol chemiluminescence (CL). Fifty-eight subjects, 25 males and 33
      females, were studied, median age 49 years (range 26-88 years). Polymorphonuclear
      cell superoxide generation was significantly higher in males and there was a
      trend towards higher pmn MPO product generation in males. Using Spearman's ranked
      correlation coefficient, monocyte superoxide generation was negatively correlated
      with age (r = -0.473, P < 0.001). No changes in the generation of MPO products
      was found. There were also trends towards a negative correlation of pmn
      cytochrome c reduction and peak luminol CL with age in males but not females.
      Since PMA directly activates protein kinase C, reduced monocyte superoxide
      generation with increasing age appears to be related to alterations in the ROS
      generating system downstream of the cell receptor. Impaired monocyte superoxide
      generation may have implications for non-specific defence against certain
      infections and early tumour growth in the elderly. Factors underlying these
      changes in monocyte function therefore require further study.

PMID- 9147367
TI  - Norepinephrine content in primary and secondary lymphoid organs is altered in
      rats with adjuvant-induced arthritis.
AB  - Chemical sympathectomy of secondary lymphoid organs with sparing of the hind
      limbs exacerbates adjuvant-induced arthritis (AA) in Lewis rats supporting a role
      for noradrenergic (NA) innervation of the immune system in AA pathology. The
      present study examines sympathetic innervation of lymphoid organs from Lewis rats
      32 days after treatment with complete Freund's adjuvant (CFA) or vehicle using
      fluorescence histochemistry for localization of catecholamines (CA) and high
      performance liquid chromatography with electrochemical detection (LCEC) for
      measurement for norepinephrine. The thymus from AA rats was significantly reduced
      in size, while secondary lymphoid organs, i.e., spleen and draining lymph nodes
      (DLN), were significantly enlarged compared with that seen in vehicle-treated
      controls. Fluorescence histochemistry revealed no apparent differences in the
      density of NA innervation, or the intensity of staining in sympathetic nerves in
      any of the secondary lymphoid organs from AA rats compared with that observed in
      control animals. However, there was an apparent increase in the density of NA
      nerve fibers in the thymus of AA rats. Norepinephrine (NE) concentration (pmol NE
      per g or mg wet weight), in the thymus from AA rats was significantly increased.
      Conversely, a significant decrease in splenic and lymph node NE concentration was
      measured in adjuvant-treated animals compared with that seen in vehicle-treated
      rats. Total NE content (pmol NE per whole organ weight) in lymphoid organs was
      not altered, except in popliteal lymph nodes (PLN), where it was increased.
      Collectively, our findings suggest that changes in NA innervation of lymphoid
      organs from AA rats result largely from increases or decreases in organ mass.
      Since NE released from NA nerves acts in a paracrine fashion, changes in lymphoid
      tissue volume that result from enhanced proliferation, migration, or cell death
      can make a significant difference in the availability of NE for interaction with
      immune target cells in these organs, even in the absence of a change in NE
      metabolism. Decreased thymic weight and increased spleen and lymph node weight
      should increase and decrease NE availability for interaction with target cells,
      respectively. Additionally, in PLN (a site where the highest concentration of
      antigen is encountered) an increase in total NE content suggests compensatory
      changes in NE metabolism.

PMID- 9147368
TI  - Alterations in sympathetic innervation of thymus and spleen in aged mice.
AB  - Age is associated with reduced immune reactivity, contributing to increased rates
      of infectious disease and cancer in old age. We have begun to assess the
      potential for sympathetic nervous system involvement in age-related immune
      dysfunction by characterizing sympathetic noradrenergic (NA) innervation in
      lymphoid organs in old animals. In the present study noradrenergic innervation of
      spleen and thymus was examined histologically and neurochemically in 2-, 12- and
      24-month old BALB/c mice. In the thymus of 2-month old animals, NA nerve fibers
      were found in the subcapsular, cortical, and cortico-medullary regions associated
      with blood vessels and septa; occasional branches from these nerve fibers entered
      the parenchyma. With increasing age and thymic involution, NA nerve fibers
      increased in density; by 24 months of age, dense plexuses were compacted among
      septa and blood vessels, and numerous linear, varicose nerve fibers were observed
      branching into the parenchyma. Thymic norepinephrine (NE) concentration (per mg
      wet weight) increased approximately 4-fold in 12-month old animals and 15-fold in
      24-month old animals. Taking the reduced thymus weight into account, total thymic
      NE at 12- and 24-month of age was equivalent to total thymic NE at 2-month of
      age, suggesting that NA innervation is maintained as the thymus involutes. In the
      spleen from 2-month old animals, NA innervation entered the white pulp with the
      central artery to innervate the periarteriolar lymphatic sheath and the marginal
      zone. At 12-month of age, histologically and neurochemically there was no change
      in splenic NA innervation. By 24-month of age, NE was increased significantly,
      independent of changes in spleen weight. Histologically, increased catecholamine
      containing fibers were apparent at 24-month of age, particularly in the
      parenchyma surrounding the central artery. The alterations in sympathetic NA
      innervation of lymphoid organs with age suggest that the sympathetic nervous
      system and NE may play a role in age-associated immune dysregulation.
      Alternatively, the changes in NA innervation may be secondary to functional
      changes within the immune system.

PMID- 9147369
TI  - The monitoring biomarker for immune function of lymphocytes in the elderly.
AB  - In this paper, we determined the number of peripheral blood lymphocytes (PBL) in
      the elderly and their proliferative response to PHA (Phytohemagglutinin). The
      data showed that the PBL number decreased with age. For the young group: 1680.0
      +/- 644.7/microliters; the 60-69 years old group: 1284.0 +/- 492.3/microliters;
      the 70-79 years old group: 987.5 +/- 309.1/microliters, P < 0.05. The OD (optical
      density) value measured by MTT method for proliferative response of PBL in the
      elderly was 0.15 +/- 0.08, which was lower than the young group 0.18 +/- 0.05.
      Also, an apparent decline of soluble IL-2 receptor (sIL-2R) release from
      activated PBL in old people was found. The results suggested that the changes of
      PBL number and sIL-2R level could be considered as an indication of immune
      function of lymphocytes in the elderly.

PMID- 9147370
TI  - Prevalence of organ-specific and non organ-specific autoantibodies in healthy
      centenarians.
AB  - In the present study we have investigated the prevalence of organ-specific and
      non organ-specific autoantibodies in 26 healthy centenarians (6 men, 20 women;
      age range 101-106 years), using as controls 54 healthy old (33 men and 21 women,
      age range 71-93) and 56 young subjects (29 men and 27 women, age range 26-60). We
      assayed sera of each group for the following organ-specific autoantibodies, anti
      gastric mucosa (anti-PCA), anti-thyroglobulin (anti-Tg) and non organ-specific
      autoantibodies, anti-cardiolipin (anti-APA IgG and IgM), anti-nuclear antigens
      (anti-ANA), anti-double strand DNA (anti-ds-DNA), anti-extractable nuclear
      antigens (anti-ENA). Finally, natural anti-alpha-galactosyl (anti-alpha-GAL)
      antibodies were also analyzed. As expected, in the old subjects there was a
      significant increase of prevalence of anti-Tg and anti-PCA autoantibodies. By
      contrast, in centenarians the prevalence of organ specific anti-Tg and anti-PCA
      antibodies was not significantly different from that observed in controls aged
      less than 60 years. The prevalence of non organ-specific autoantibodies anti-APA
      (IgG), anti-APA (IgM), anti-ANA, was significantly increased both in the elderly
      and centenarians when compared with the prevalence observed in sera from the
      young. Anti-ENA and anti-dsDNA antibodies were not detected in all groups
      studied. Finally, the prevalence of natural anti-alpha-GAL antibodies
      significantly increases with age, including centenarians. In conclusion, we
      confirm and extend the results previously obtained by other authors. In fact, as
      already described, the prevalence of organ-specific autoantibodies in the elderly
      is not seen after the tenth decade of life. Interestingly, the prevalence of non
      organ-specific autoantibodies is instead increased in these subjects, suggesting
      that different mechanisms are involved in the pathogenesis of these
      autoantibodies. Particularly, these autoantibodies could be the expression of a
      damaged tissue process rather than of an autoimmune one, as suggested by data
      concerning natural antibodies.

PMID- 9147371
TI  - HLA and longevity or aging among Shanghai Chinese.
AB  - Twenty-two centenarians and one hundred and seventy-nine nonagenarians (mean age
      93 +/- 1.04 years) in the Shanghai Region of China were phenotyped for alleles of
      A (13 types), B (21 types) and C (6 types) loci of the human leukocyte antigen
      (HLA). The frequencies of HLA antigens were compared with 211 healthy adults
      whose ages ranged from 20 to 50 years. It was observed that A9 was highly
      associated with longevity (frequency in the longevity group is 38%, the control
      group 24%, P = 0.002). A30 showed marked inverse correlation (frequency in the
      longevity group is 8%, the control group 17%, P = 0.008). Cw3, Cw6 and Cw7 were
      also inversely correlated (P = 0.02, 0.04 and 0.02, respectively). Thus, it is
      likely that A9 may contribute to longevity while A30, Cw3, Cw6 and Cw7 may be
      associated with aging. The average superoxide dismutase (SOD) contents of
      erythrocytes in 48 cases with the HLA-A9 (without A30) antigen in the longevity
      group and in 13 cases with the HLA-A30 (without A9) antigen in the control group
      were 555 +/- 96 and 593 +/- 58 micrograms/gHb, respectively (t = 1.375, P >
      0.05).

PMID- 9147372
TI  - beta-Amyloid-induced IL-1 beta release from an activated human monocyte cell line
      is calcium- and G-protein-dependent.
AB  - The proinflammatory cytokine, interleukin-1 (IL-1) is elevated in the Alzheimer's
      disease (AD) brain. Studies from our laboratory have demonstrated that beta
      amyloid (A beta) 1-42, fibrillar A beta 1-40 and A beta 25-35 induce the release
      of IL-1 beta from activated THP-1 cells, a human monocyte cell line. A beta also
      is chemotactic for primary rodent microglia and peritoneal macrophages. We
      hypothesize that A beta is a chemokine and induces these responses by interaction
      with chemotactic receptors. If this is true, then these A beta-induced responses
      should be calcium-dependent and require activation of pertussis toxin-sensitive G
      proteins. To test this hypothesis, THP-1 cells were grown in culture with
      lipopolysaccharide (LPS) and incubated with A beta 1-42 (5 muM) in the presence
      and absence of a calcium chelator, an inhibitor of intracellular calcium
      mobilization, a calcium channel blocker, or pertussis toxin, a bacterial
      endotoxin which uncouples G proteins from receptors by catalyzing the ADP
      ribosylation of cysteine near the carboxy-terminus of the alpha subunit. The
      media was collected and IL-1 beta present in the media was measured using an
      ELISA. Treatment of LPS-activated THP-1 cells with A beta 1-42 significantly
      elevated IL-1 beta released into the media as previously shown. Addition or
      ethylene glycol-bis (beta-aminothyl ether) N,N,N'N'-tetraacetic acid (EGTA) (0.5
      mM), a calcium chelator, to the media blocked A beta-induced IL-1 beta release,
      but had no effect on LPS-activated THP-1 cell release of IL-1 beta. The presence
      of 3,4,5-trimethoxybenzoic acid 8-(diethyl amino)-octyl ester (TMB-8), an
      inhibitor of intracellular calcium mobilization, as well as nickel chloride, a
      non-specific calcium channel blocker, in the media also inhibited A beta-induced
      IL-1 release from LPS-activated THP-1 cells. IL- 1 beta release from activated
      THP-1 monocytes incubated with TMB-8 and nickel chloride without A beta remained
      at baseline values. Pretreatment of THP-1 monocytes with pertussis toxin for 4 h,
      followed by LPS activation and incubation with A beta, antagonized the release of
      IL-1 beta from these cells, but did not alter IL-1 beta release from activated
      THP-1 monocytes. These data suggest that A beta-induced IL-1 beta release from
      these cells is calcium-dependent and requires the activation of specific G
      proteins. These findings are consistent with known second messengers that are
      activated following stimulation of chemotactic receptors.

PMID- 9147373
TI  - Increased incidence of anti-beta-amyloid autoantibodies secreted by Epstein-Barr
      virus transformed B cell lines from patients with Alzheimer's disease.
AB  - During the past several years, evidence has been accumulated to support the
      thesis that immunological factors may play some role in Alzheimer's disease (AD).
      We have characterized the reactive antigens detected by certain monoclonal
      antibodies secreted by Epstein-Barr virus (EBV)-transformed B cell lines from the
      peripheral blood of AD patients and controls. Autoantibodies against beta-amyloid
      protein beta-amyloid protein (beta-A) in amyloid plaques and blood vessels and in
      enzyme-linked immunosorbent assays (ELISA) have been reported in four cell lines
      derived from an AD patient. In this study, over 3300 EBV-transformed B cell lines
      from thirteen individuals were tested in ELISAs for antibodies against beta-A
      peptides. Significantly more autoantibodies against beta-A (1-40) were found in
      the AD group, 2.26 +/- 0.62% (39/1794 cell lines) than in the control group, 0.28
      +/- 0.36% (5/1552 cell lines) with P < 0.005. These new antibodies did not react
      with plaques or amyloid deposits in blood vessels. In contrast to the four plaque
      reactive autoantibodies which reacted better with beta-A (1-40) than with beta-A
      (1-28), 70% of these anti-beta-A (1-40) antibodies reacted as well or better with
      beta-A (1-28). Many of them were also reactive with beta-A (1-16). Tested against
      a panel of cytoskeletal proteins and Hela cells, many of these anti-beta-A (1-40)
      antibodies appear to be polyreactive. The higher incidence of anti-beta-A
      antibody secreting B cells in AD patients provides further evidence that
      autoimmunity may play a role in AD.

PMID- 9147374
TI  - Interactions of the Alzheimer beta amyloid fragment (25-35) with peripheral blood
      dendritic cells.
AB  - We have previously demonstrated that soluble amyloid beta protein (A beta)
      induces IL-2 receptor expression and proliferation in peripheral T cells from
      young and old healthy individuals, but not from patients with Alzheimer's disease
      (AD). It seemed of interest to examine how the immune system would react upon
      stimulation with A beta in its aggregated form. It was the aim of this study to
      define interactions between the spontaneously aggregating A beta (25-35) and
      antigen-presenting cells. Human dendritic cells (DC), propagated from the
      peripheral blood of young healthy individuals, were incubated with A beta (25-35)
      and its effects on DC survival, cytokine release, and surface marker expression
      were monitored. The question whether DC could present amyloid to T cells was also
      addressed. We demonstrated that A beta (25-35) does not induce DC apoptosis or
      necrosis. This was shown by electron microscopy as well as by nuclear staining
      with propidium iodide. Some peptide aggregates were found in intracellular
      vacuoles of DC. This process did not increase production of TNF alpha and did not
      change the surface expression of CD18, CD11a or CD11b. A decreased surface
      expression of MHC class II molecules was, however, noted. DC pulsed with A beta
      aggregates were unable to stimulate T cells in an autologous coculture system.
      The results demonstrate that amyloid may escape immune recognition by its failure
      to activate antigen-presenting cells and by inhibiting MHC class II surface
      expression.

PMID- 9147376
TI  - Creating knowledge relevant for public health applications in immunology and
      aging.
AB  - New types of knowledge are needed to meet public health challenges that are
      growing in scope and complexity. While contemporary life exposes people to
      interactions among an increasingly complex array of biological and psychosocial
      influences that can damage health, the complexity inherent in disease processes
      is generally neglected in research for public health applications. Health
      promotion and the prevention and control of diseases, including chronic diseases
      that develop over long periods of time, depend on strengthening the resistance of
      human hosts. The effective functioning of the immune system is an essential
      pathway through which host defenses operate to protect health. Research on
      immunology and aging can help to provide the types of new knowledge needed for
      effective health promotion to meet public health challenges in a period of global
      aging.

PMID- 9147375
TI  - Attenuated stress responses in young and old human lymphocytes.
AB  - Aging generally is understood to be a period defined by altered responses to
      physiological stress. At the molecular level, several stress responses involving
      specific gene expression have been revealed, and thermal stress has been tightly
      linked to induction of the heat shock gene family (D.A. Jurivich. In E. Bittar
      (ed.), Principles of Medical Biology, Vol. 4, JAI press, San Diego, 1996, pp. 411
      462). Perturbations in heat shock gene transcription consistently have been noted
      in senescent cells from all species examined thus far. Because heat shock
      proteins serve several vital functions in the immune system, changes in the
      thermal stress response could potentially contribute to immunosenescence.
      Inadequate promoter priming by the transactivator or heat shock genes, heat shock
      factor 1 (HSF1), is thought to account for age-dependent diminution in expression
      of these genes, although the exact mechanism for this loss is not clearly
      understood. We have found that human lymphocytes exhibit an age-dependent loss in
      HSF1-DNA binding, although a range of binding has been observed in both young and
      old donor cells. This report characterizes a subset of young and old human donor
      lymphocytes that are non-responders to thermal stress defined by the absence of
      HSF1-DNA binding after a 42 degrees C heat shock. Whole cell extracts from these
      donor cells have the capacity to inhibit HSF1-DNA binding when mixed with pre
      activated HSF1 from HeLa cells. This inhibitory activity is lost upon heat
      denaturation and does not appear to be protease mediated. Serial passage of
      lymphoblasts recapitulates loss of heat inducible HSF1-DNA observed in old donor
      lymphocytes, thus suggesting that loss of replicative potential and aging lead to
      altered stress responses. Uncoupling of the thermal response and its potential
      relevance to apoptosis and aging are discussed.

PMID- 9147377
TI  - Evidence for local production of acute phase response apolipoprotein serum
      amyloid A in Alzheimer's disease brain.
AB  - Acute phase serum amyloid A (A-apoSAA), but not constitutive apoSAA (C-apoSAA),
      was identified by Western blotting experiments in brain protein extracts from
      eight of nine patients with Alzheimer's disease (AD), one with a brain tumor and
      one with multiple sclerosis. A-apoSAA was not detected in six subjects with
      Pick's or Lewy Body disease or three other non-AD brain specimens. Apolipoprotein
      A-I and albumin were not found in any of the brain protein extracts. A-apoSAA
      mRNA was detected in AD brain by reverse transcription-polymerase chain reaction
      (RT-PCR). These data suggest that apoSAA is locally produced in AD brain and that
      investigation of the neuroinflammatory effects of this injury specific
      apolipoprotein is warranted.

PMID- 9147378
TI  - Fractal dimensions of short EEG time series in humans.
AB  - Fractal dimensions has been proposed as a useful measure for the characterisation
      of electrophysiological time series. But one of the problems of this approach, is
      the difficulty to record time series long enough of determine the 'real' fractal
      dimension. Nevertheless it is possible to calculate fractal dimensions for very
      short data-segments. Using time series of different length it is possible to
      show, that there is a monotoneous relation between fractal dimension and the
      number of data-points. This relation could be further interpreted with the help
      of an extrapolation scheme. In addition this effect is also seen with surrogate
      data, generated from that signal. We conclude that it is feasible to use fractal
      dimension as a tool to characterise the complexity for short
      electroencephalographic (EEG) time series, but it is not possible to decide
      whether the brain is a chaotic system or not.

PMID- 9147379
TI  - Ryanodine receptors from rabbit skeletal muscle are reversibly activated by
      rapamycin.
AB  - In this report we demonstrate that the immunosuppressive drug, rapamycin, can
      reversibly activate the skeletal muscle ryanodine receptor calcium release
      channel (RyR) in terminal cisternae vesicles incorporated into planar lipid
      bilayers. This reveals a second mechanism of activation of RyRs by rapamycin.
      Irreversible channel activation and openings to subconductance levels are seen
      when rapamycin forms a complex with and removes the tightly bound 12 kDa FK506
      binding protein (FKBP12) from the RyR. We show here that micromolar rapamycin
      activates RyRs which were previously 'stripped' of > 95% of their FKBP12s.
      Rapamycin caused a 6-fold increase in mean current, which was largely reversible,
      but no increase in the fraction of openings to subconductance levels. Therefore
      native RyRs, stripped of FKBP12, are directly activated by the macrocyclic
      lactone, rapamycin.

PMID- 9147380
TI  - Role of cerebellar granule cell-specific GABAA receptor subtype in the
      differential sensitivity of [3H]ethynylbicycloorthobenzoate binding to GABA
      mimetics.
AB  - Binding of [3H]ethynylbicycloorthobenzoate ([3H]EBOB) to the gamma-aminobutyric
      acid type A (GABAA) receptor of cultured cerebellar granule neurons is inhibited
      by GABA, muscimol and 3-aminopropanesulfonic acid with IC50 values of 69-250 nM.
      Sensitivity to these GABA mimetics is lower by 3-4-fold for cerebellum and 10-20
      fold for cerebral cortex, midbrain, and pons and medulla, a differential
      sensitivity by brain region and cell type consistent with earlier findings using
      tert-[35S]butylbicyclophosphorothionate and GABA. In contrast, the inhibitory
      potencies of two chloride channel blockers, alpha-endosulfan and picrotoxinin, do
      not differ in these assays. The hypothesis that this pharmacological profile is
      conferred by the alpha 6 subunit specific to cerebellar granule cells is
      supported by the finding that forskolin (which downregulates the alpha 6 subunit)
      but not the inactive dideoxyforskolin markedly decreases the sensitivity of
      [3H]EBOB binding to GABA without affecting inhibition by alpha-endosulfan.

PMID- 9147381
TI  - Knee joint inflammation attenuates spinal FOS expression after unilateral paw
      formalin injection in rat.
AB  - Carrageenan-induced knee joint inflammation evoked a transient spinal FOS protein
      expression in neurons localized in the apical region of laminae I-III with peak
      activity observed 2 h after inflammation. Consistent with previously published
      observations, paw formalin injection evoked a distinct pattern of FOS protein
      expression in L3-L5 spinal segments. The majority of FOS-positive neurons were
      localized in the superficial dorsal horn (laminae I-II). Laminae V and VI
      contained moderate numbers of labeled neurons and only a few labeled nuclei were
      visible in laminae VII-X. In contrast, ipsilateral paw formalin injection, if
      administered 4 h after carrageenan-induced knee inflammation, evoked
      significantly fewer FOS positive neurons in all laminar and segmental levels
      analyzed as compared with formalin injected animals but without previous knee
      joint inflammation. These data indicate that primary acute or subacute
      nociceptive input may evoke central processes that are characterized by an
      inducible form of central inhibition which then may serve to modulate the
      subsequent spinal effect of superimposed nociceptive peripheral stimulation.

PMID- 9147382
TI  - Eugenol protects neuronal cells from excitotoxic and oxidative injury in primary
      cortical cultures.
AB  - We examined the neuroprotective efficacy of eugenol against N-methyl-D-aspartate
      (NMDA)-, oxygen-glucose deprivation-, and xanthine/xanthine oxidase-induced
      neurotoxicity in primary murine cortical cultures. Eugenol (100-300 microM)
      attenuated NMDA (300 microM)-induced acute neurotoxicity by 20-60%. At the same
      concentration range, eugenol also inhibited NMDA (300 microM)-induced elevation
      in neuronal 45Ca2+ uptake by 10-30%. In the oxygen-glucose deprivation (50 min)
      neurotoxicity, eugenol (100-300 microM) prevented acute neuronal swelling and
      reduced neuronal death by 45-60% in a concentration-dependent fashion. Oxidative
      neuronal injury induced by xanthine/xanthine oxidase was also significantly
      reduced (75-90%) by eugenol (100- 300 microM) addition. These results suggest
      that eugenol may play a protective role against ischemic injury by modulating
      both NMDA receptor and superoxide radical.

PMID- 9147383
TI  - Histochemistry in rat brain and spinal cord with an antibody directed at the
      cholecystokininA receptor.
AB  - Various neurobiological evidence indicates that A-subtype cholecystokinin (CCKA)
      receptors are widely distributed through the mammalian neuroaxis despite the
      sparse localization found by receptor autoradiography. To address this paradox,
      immunohistochemistry has been performed in rat brain and spinal cord using an
      antibody directed at a portion of the amino terminal sequence of the CCKA
      receptor. Immunoreactivity, visualised using diaminobenzidine, was widely and
      topographically distributed being most concentrated in medulla and spinal cord.
      Many forebrain areas contained specifically labelled neurones, notably the
      nucleus accumbens, septum, stria terminalis, habenula, substantia nigra, ventral
      tegmental area and lateral geniculate nucleus. In medulla, heavily labelled
      perikarya were found in parabrachial and trigeminal nuclei, while in spinal cord
      immunoreactivity was localized in dorsal horn. Localization of immunoreactivity
      was consistent with the reported distribution of CCKA receptor-mediated
      mechanisms. Our observations represent the first attempt to describe the
      localization of the CCKA receptor in brain using immunohistochemistry and support
      its wide functional involvement in the central nervous system.

PMID- 9147384
TI  - Afferent connections of the nucleus accumbens of the snake, Elaphe guttata,
      studied by means of in vitro and in vivo tracing techniques in combination with
      TH immunohistochemistry.
AB  - The aim of the present study was to determine the afferent connections of the
      nucleus accumbens in snakes, in particular its catecholaminergic input. For that
      purpose, in vitro and in vivo applications of retrograde tracers in the nucleus
      accumbens of Elaphe guttata were combined with tyrosine hydroxylase (TH)
      immunohistochemistry. Both techniques revealed telencephalic inputs to the
      nucleus accumbens originating from the diagonal band of Broca, ventral pallidum,
      amygdaloid complex, and dorsal cortex. Major diencephalic inputs arise from the
      dorsomedial thalamic nucleus and the hypothalamus. In the brainstem, a few
      retrogradely labeled cells were observed in the raphe nucleus and the locus
      coeruleus. Considerably more cells were found in the midbrain tegmentum. Within
      the confines of the locus coeruleus and, in particular, the midbrain tegmentum,
      retrogradely labeled cells stained also for TH suggesting that those areas
      constitute the major catecholaminergic input to the nucleus accumbens of snakes.
      The experimental approach used in the present study, in particular the in vitro
      technique, seems to be very suited for studying the development of basal ganglia
      organization of reptiles in the near future.

PMID- 9147385
TI  - Distribution and characteristics of cholecystokinin-like immunoreactivity in the
      olfactory bulb of the cat.
AB  - The distribution and characteristics of cholecystokinin (CCK)-like immunoreactive
      (LIR) nerve fibers was examined in the cat olfactory bulb using
      immunohistochemistry. CCK-LIR cell bodies were not found; fine varicose CCK-LIR
      fibers were observed in the most layers. In the main olfactory bulb, no staining
      was seen in the olfactory nerve layer and white matter. The directions of CCK-LIR
      fibers in the glomerular, external plexiform and mitral cell layers were
      generally perpendicular to the bulbar surface; those in the deep granule cell
      layer were parallel; and those in the internal plexiform and superficial granule
      cell layers were mixed. In the accessory olfactory bulb, CCK-LIR fibers were
      localized only in the granule cell layer. The presence of CCK-LIR fibers of the
      cat olfactory bulb may be involved in the modulation of olfactory transmission.

PMID- 9147386
TI  - Ketoprofen, a non-steroidal anti-inflammatory drug prevents the late-onset
      reduction of muscarinic receptors in gerbil hippocampus after transient forebrain
      ischemia.
AB  - Ischemia-induced hippocampal late-onset reduction of muscarinic acetylcholine
      receptors (LORMAR) begins as late as 7 days after transient forebrain ischemia in
      the gerbil, but it precedes to completion of neuronal death in the CA1 region. We
      previously reported that post-ischemic administration of cyclosporin A prevented
      LORMAR with suppression of astroglial and microglial activation. In the present
      study, we showed that the chronic post-ischemic administration of a non-steroidal
      anti-inflammatory drug, ketoprofen (5 mg/kg, subcutaneously, twice a day for 14
      days) significantly reduced LORMAR both 14 days and 21 days after 5-min transient
      ischemia. This protective effect of ketoprofen against LORMAR suggests that the
      non-steroidal anti-inflammatory drugs is clinically efficacious in the treatment
      of LORMAR, a sequela of cerebral ischemia.

PMID- 9147387
TI  - The rhinophores sense pheromones regulating multiple behaviors in Aplysia
      fasciata.
AB  - Pheromones released during mating and egg laying in Aplysia facilitate various
      aspects of behavior. We now show that the chemosensory rhinophores sense these
      pheromones. Ablating the rhinophores causes a significant decrease in the time
      spent mating. In addition, the lesion blocks the increases of feeding in response
      to pheromones released by egg cordons and by mating conspecifics. Respiratory
      pumping is significantly increased in response to egg cordons, mating
      conspecifics and egg laying hormone (ELH). The increase in response to egg
      cordons is blocked by ablating the rhinophores, but not by lesioning the
      osphradium, a second chemosensory organ.

PMID- 9147388
TI  - Histamine H1 receptors and inositol phosphate formation in rat thalamus.
AB  - In membranes of rat thalamus the density of histamine H1 receptors, as estimated
      from saturation curves with [3H]mepyramine, was 66 +/- 5 fmol.mg protein-1 (Kd
      1.3 +/- 0.1 nM). Specific [3H]mepyramine binding was inhibited by mepyramine
      (best fit to one-site model, Kd 2.2 +/- 0.2 nM) and by histamine (best fit to a
      two-site model, Ki high 0.35 +/- 0.04 microM and 54 +/- 7% of binding sites; Ki
      low 7.0 +/- 1.1 microM). In the presence of 300 microM GppNHp (5'
      guanylylimidodiphosphate) the inhibition curve for histamine best-fit to a one
      site model (Ki 3.1 +/- 0.3 microM). In cross-chopped slices and in the presence
      of 10 mM LiCl, histamine stimulated the accumulation of total [3H]inositol
      phosphates ([3H]IPs) with a maximum effect of 163 +/- 3% of basal accumulation,
      EC50 of 8 +/- 2 microM and Hill coefficient (nH) of 0.8 +/- 0.1. [3H]IPs
      accumulation induced by 100 microM histamine was inhibited by the selective H1
      antagonist mepyramine (1 microM, 90 +/- 8% inhibition; Ki 2.1 +/- 0.4 nM) but not
      by 10 microM ranitidine (a selective H2 antagonist) or 1 microM thioperamide (a
      selective H3 antagonist). These results show the presence in rat thalamus of
      functional H1 receptors coupled in inositol phosphate accumulation.

PMID- 9147389
TI  - The promoter of macrophage colony-stimulating factor receptor is active in
      astrocytes.
AB  - Macrophage colony-stimulating factor (M-CSF) is a hematopoietin whose actions are
      essential for growth and survival of macrophages, placental development,
      ramification of microglia and tumor progression. The expression of the receptor
      for macrophage colony-stimulating factor (c-fms) is regulated by two distinct
      promoters: distal and proximal. The distal promoter is active in trophoblasts
      during embryogenesis and the proximal promoter directs expression to the cells of
      myeloid lineage. Here we report the generation of transgenic mice expressing beta
      galactosidase under the control of the human proximal c-fms promoter and
      demonstrate the promoter activity in astrocytes, cells of neurological origin
      that partially take over the role of the macrophages in the central nervous
      system. Enzymatic activity of beta-galactosidase was detected in homogenated
      spleen, bone marrow and brain and in the cell extracts from peritoneal
      macrophages of transgenic mice. Immunohistochemical staining of brain showed the
      presence of beta-galactosidase in astrocytes. We hypothesize that M-CSF released
      by astrocytes, upon stimulation by lipopolysaccharide (LPS), tumor necrosis
      factor alpha (TNF alpha) or interleukin-1 (IL-1), regulates the expression of its
      own receptor.

PMID- 9147390
TI  - Calcium- and myristoyl-dependent subcellular localization of the neuronal calcium
      binding protein VILIP in transfected PC12 cells.
AB  - Wild-type neuronal calcium-binding protein VILIP (visinin-like protein), and a
      myristoylation mutant of VILIP which lacks the consensus sequence for N-terminal
      myristoylation, have been stably transfected in PC12 cells. Immunocytochemical
      studies of VILIP-transfected PC12 cells have revealed the wild-type VILIP is
      strongly concentrated at the cell membrane, particularly at cell-cell contact
      sites, but is also distributed throughout the cytosol at moderate levels. In
      contrast, myristoylation-mutant VILIP shows a more even distribution, with
      significantly less association at cell-cell contact sites. Western blot analysis
      of subcellular fractions has shown that wild-type VILIP associates in a calcium
      dependent manner with membrane fractions, whereas the myristoylation mutant only
      weakly associates with this fraction. Therefore, a calcium-myristoyl switch seems
      to be a major, but not sole determinant for the association of VILIP with
      membranes in living cells.

PMID- 9147391
TI  - GMP protects against quinolinic acid-induced loss of NADPH-diaphorase-positive
      cells in the rat striatum.
AB  - When injected into the rat striatum, quinolinic acid causes dose-dependent
      widespread cell death. All cell types, including the NADPH-diaphorase-positive
      neurons appear to be sensitive to the toxin. The latter cells are destroyed by
      quinolinic acid injections of 180 nmol per striatum, this effect being blocked by
      the concomitant administration of 5 mg/kg of the non-competitive N-methyl-D
      aspartate antagonist MK-801. We report that guanosine-5'-monophosphate (GMP), at
      a dose of 360 nmol, is equally effective in protecting the diaphorase-positive
      cells against quinolinate toxicity.

PMID- 9147392
TI  - Acute effect of c-fos antisense oligodeoxynucleotide on hippocampal partial
      seizures elicited by electrical stimulation in rats.
AB  - We examined the effects of antisense oligodeoxynucleotides (ODNs) to c-fos mRNA
      on hippocampal partial seizures in rats. As control, sense and scrambled control
      ODNs were also tested. Each ODN (10 nmol/10 microliters) was injected into the
      lateral ventricles for 2 consecutive days. Fifteen hours after the last
      injection, electrical stimulation was delivered to assess the effects on after
      discharge threshold and afterdischarge duration (ADD). One hour after seizures, c
      Fos and Jun-B immunocytochemistries were performed. Antisense ODNs significantly
      decreased ADD and control ODNs failed to change any parameters. In the antisense
      ODNs group, c-Fos expression occurred ipsilateral to the stimulation site in
      dentate granule cells, while Jun-B expression was seen bilaterally. In the
      majority of control ODNs animals, c-Fos and Jun-B expression in dentate granule
      cells occurred bilaterally. These findings suggest that the injection of
      antisense ODNs selectively inhibit contralateral c-Fos expression and that c-fos
      plays a key role in hippocampal excitability and seizure expression during
      hippocampal partial seizures.

PMID- 9147393
TI  - Dietary preferences in monosodium glutamate-lesioned rats: age-variable influence
      of hypothalamic neuropeptide Y.
AB  - In this study, we measured hypothalamic neuropeptide Y (NPY) and the food
      preference in weanling and adult monosodium glutamate (MSG)-lesioned and control
      rats. The MSG lesion was induced by three subcutaneous injections (4 g/kg body
      wt) during the first week of life of the rats. All treated and control weanling
      rats strongly preferred a high carbohydrate (HC) diet to a high fat (HF) diet.
      Adult control rats ate 60% more HF diet (P < 0.001) and 25% less HC diet (P <
      0.01) than MSG-treated rats. At weaning and in adulthood, NPY concentrations in
      MSG-rats were markedly lower in the arcuate and paraventricular nuclei (P < 0.01
      or less) than in control rats. The MSG treatment did not affect carbohydrate
      preference observed at weaning. It was associated with a limited development of
      fat appetite in adulthood. NPY could influence the dietary preferences more in
      adulthood, likely when all neuropeptidergic systems are mature.

PMID- 9147394
TI  - Scopolamine reversal of tremor produced by low doses of physostigmine in rats:
      evidence for a cholinergic mechanism.
AB  - In order to provide evidence for the involvement of cholinergic mechanisms in a
      low-dose physostigmine-induced tremor, a novel technique for measuring forelimb
      tremor in rats was used. Rats that were administered physostigmine (0.05 and 0.1
      mg/kg, s.c.), scopolamine (0.1 and 0.2 mg/kg, s.c.), and combinations of the two
      drugs, pressed a force-sensing operandum while a computer measured force output
      and performed Fourier analyses on resulting force-time waveforms. When given
      alone, both drugs decreased task engagement but mutually antagonized this effect
      when given together. Physostigmine increased tremors as well as peak force.
      Scopolamine decreased tremor and force when administered alone and reversed
      physostigmine-induced increases in force and tremor. Physostigmine's low-dose
      induction of increased tremor during rats' skilled forelimb use appears to have a
      prominent cholinergic component.

PMID- 9147396
TI  - Promotion of neurogenesis in mouse olfactory neuronal progenitor cells by
      leukemia inhibitory factor in vitro.
AB  - Olfactory neuronal progenitor cells were partially purified from the olfactory
      epithelia of 14.5-day-old mouse embryos by an immuno-killing method with an
      antibody against neural adhesion molecule (N-CAM). Immunostaining study showed
      that about 60% of the population after immunokilling, was class-III beta-tubulin
      /keratin-neuronal progenitor cells and that they differentiated into N-CAM+/class
      III beta-tubulin+ neurons in a chemically-defined medium within 1 day in culture.
      A part of them proliferated prior to their neuronal differentiation as determined
      by the incorporation of bromodeoxyuridine (BrdU) into neuronal nuclei. Leukemia
      inhibitory factor (LIF), but not ciliary neurotrophic factor or interleukin-6,
      increased the proportion of the BrdU-labeled neurons in vitro. These results
      suggest LIF promotes the neurogenesis in the olfactory neuronal progenitor cells.

PMID- 9147395
TI  - Role of pre-inspiratory neurons in vestibular and laryngeal reflexes and in
      swallowing and vomiting.
AB  - Fifteen pre-inspiratory (Pre-I) neurons were extracellularly recorded in the pre
      Botzinger complex and their involvements in vestibular (VN) and superior
      laryngeal (SLN) nerve reflexes and in fictive swallowing and vomiting were tested
      in decerebrated and artificially ventilated cats. Both type I (1 of 9) and type
      II (1 of 6) pre-I neurons could project to the contralateral ventral respiratory
      group region. Pre-I neurons changed their firing during VN and SLN respiratory
      reflexes and fictive swallowing and vomiting; different response properties were
      observed among individual pre-I neurons. These results suggest that pre-I neurons
      are a population of heterogeneous and multi-functional propriobulbar neurons.

PMID- 9147397
TI  - Choline acetyltransferase mRNA expression in the striatal neurons of patients
      with Alzheimer's disease.
AB  - Besides cortical pathology, Alzheimer's disease (AD) is associated with a massive
      loss of cholinergic neurons in the basal forebrain. The resulting cortical
      cholinergic depletion is thought to contribute to the major cognitive impairment
      described in Ad. A selective loss of cholinergic neurons has also been observed
      in the ventral striatum, despite the lack of any major neurochemical dysfunction
      in the striatum of patients with AD. To examined possible changes in the
      functional activity of the neurons that remain in the striatum of AD patients,
      the expression level of the gene coding for choline acetyltransferase (ChAT) was
      evaluated using in situ hybridization in the caudate nucleus, putamen and ventral
      striatum. Quantitative analysis showed (i) a marked decrease in the number of
      ChAT mRNA-positive neurons in the ventral striatum, and (ii) significantly
      reduced ChAT mRNA expression in the surviving cholinergic neurons of the ventral
      striatum, whereas it was only slightly decreased in those of the dorsal striatum.
      Our data support the hypothesis of a down-regulated expression of ChAT in
      striatal cholinergic neurons, especially in those most vulnerable to the
      neurodegenerative process. The subnormal ChAT mRNA content may be the consequence
      of changes in the level of transcription of the ChAT gene, possibly in relation
      to sustained suffering still present at the late stages of this disease.
      Furthermore, the involvement of the ventral striatum in Alzheimer's disease may
      account for some of the behavioral and motor dysfunctions often observed in
      patients with AD.

PMID- 9147399
TI  - Metabotropic glutamate receptor subtype-1 alpha (mGluR1 alpha) immunoreactivity
      in ependymal cells of the rat caudal medulla oblongata and spinal cord.
AB  - Immunohistochemical study of the distribution of glutamate receptor subunits 1-4
      (GluR1-4), NMDA receptor subunit 1 and metabotropic glutamate receptor subtypes 1
      3 (mGluR1-3) in the ependymal cells of the caudal medulla oblongata and upper
      thoracic spinal cord was carried out. The results showed that ependymal cells and
      tanycytes expressed only the metabotropic receptor subtype, mGluR1 alpha. Some of
      the mGluR1 alpha-positive long basal processes of the tanycytes reached the pia
      mater; some made contact with capillaries. It was suggested that the activity of
      the these mGluR 1 a-positive tanycytes may be regulated by the CSF and blood. The
      presence of many mGluR1 alpha positive fibres in the area postrema suggests that
      mGluR1 alpha subtype in this region may be involved in cardiovascular regulation.

PMID- 9147398
TI  - Reduced activity in the extrastriate visual cortex of individuals with strabismic
      amblyopia.
AB  - In order to examine the relationship between reduced visual acuity in human
      strabismic amblyopia and the cortical activation pattern, we studied, by use of
      positron emission tomography (PET) and the H2(15)O bolus technique, changes in
      the regional cerebral blood flow (rCBF) induced by monocular visual stimulation
      of 8 individuals with this disorder. Individual amblyopic thresholds for
      monocular detection of the checkerboard pattern were employed as stimuli for both
      eyes during PET scans. Statistical analysis of subtracted images showed
      significant increases in rCBF (P < 0.05) by the stimulation of the sound eye
      localized bilaterally to Brodmann's areas (BAs) 17-19. The cortical response
      evoked by the amblyopic eye was significantly reduced (P < 0.05) in the
      ipsilateral BAs 18, 19. These results suggest that the reduction in contrast
      sensitivity (pattern vision) in amblyopia is coupled with deactivation in
      identifiable regions of occipital visual areas, including ipsilateral BAs 18,19.

PMID- 9147400
TI  - Evidence of P2Y-purinoceptor mediated bladder neck smooth muscle post-contractile
      relaxation in the male mini-pig.
AB  - The functional role of non-adrenergic non-cholinergic (NANC) nerves in the
      autonomic control of the male mini-pig bladder neck was investigated in the
      present study. Electrical stimulation of muscle strips from male mini-pig bladder
      neck showed biphasic response with initial phasic contraction followed by post
      contractile relaxation. Electrical stimulation in the presence of four autonomic
      blockers (atropine 10(-6) M, propanolol 10(-6) M, phentolamine 10(-6) M) showed
      suppression of 68 +/- 15% of the contractile response (P < 0.05, n = 8) but no
      significant change in the relaxation response. Alpha-chymotrypsin 2 U/ml, L-NG
      monomethyl-L-arginine acetate (a nitric oxide synthetase inhibitor) 10(-4) M, 8
      phenylthlophylline (a P1-purinoceptor antagonist) 10(-6) M, and pyridoxal
      phosphate-6-azophenyl-2', 4'-disulphoric acid tetrasodium salt (a P2Y
      purinoceptor antagonist) 3 x 10(-5) M did not alter the NANC response
      significantly. On the other hand, reactive blue-2 (a P2Y-purinoceptor antagonist)
      3 x 10(-5) significantly reduced the relaxation by 79 +/- 9%. The result
      suggested that the P2Y-purinoceptor is involved in the electrically induced NANC
      post-contractile relaxation of the mini-pig bladder neck smooth muscle.

PMID- 9147401
TI  - Neuronal nicotinic receptor operates slow Ca2+ mobilization at mouse muscle
      endplate.
AB  - The contribution to neuromuscular functions by neuronal nicotinic acetylcholine
      receptor (nAChR) expressed at skeletal muscle endplate was investigated using
      intracellular Ca2+ measurements. A neuronal nAChR blocker, methyllycaconitine
      (MLA), depressed non-contractile Ca2+ mobilization without affecting muscle nAChR
      activity in nerve-stimulated mouse diaphragm muscle, after cholinesterase
      inhibition. Confocal imaging demonstrates that the MLA-sensitive Ca2+
      mobilization also occurred at the endplate in single flexor digitorum brevis
      muscle cells as the slow component of two-phasic Ca2+ elevation after the
      prolonged nicotinic stimulation. A monoclonal antibody to alpha 1 subunit of
      muscle nAChR depressed the fast but not the slow component. Thus, muscle neuronal
      nAChR can induce the localized rise of Ca2+ at the postjunctional sites.

PMID- 9147402
TI  - A role for adenosine in the regulation of long-term depression in the adult rat
      hippocampus in vitro.
AB  - We describe how endogenous adenosine can prevent the induction of homosynaptic
      long-term depression (LTD) in the CA1 region of slices of adult rat hippocampus.
      Neither of two consecutive periods of prolonged low frequency stimulation (LFS; 1
      Hz, 900 stimuli) of the Schaffer collateral-commissural fibres resulted in the
      induction of LTD in the CA1 region of hippocampal slices from adult (8-30 week)
      animals. However, in the presence of adenosine deaminase or the selective
      adenosine A1 receptor antagonist, 1,3-dipropyl-8-cyclopentyl-xanthine (DPCPX),
      LTD was induced by each of the first and second of two periods of LFS. The first
      period of LFS did not, but the second period of LFS did, induce LTD in the
      presence of DPCPX and the NMDA receptor antagonist, D-2-amino-5
      phosphonopentanoate (AP5). The present results show that A1 receptor activation
      by endogenous adenosine can prevent the induction of LTD in the adult
      hippocampus.

PMID- 9147403
TI  - Inter-individual differences in the effects of acute stress on the sleep
      wakefulness cycle in the rat.
AB  - It has been described that an acute immobilization stress (IS) modifies
      subsequent paradoxical sleep (PS). However, its effects are complex because some
      subjects remain unaffected. This discrepancy might result from constitutive inter
      individual psychobiological differences. In order to test this hypothesis, an
      inter-individual analysis of sleep patterns and their modifications after 60 min
      IS has been performed. Even though global analysis showed a PS increase after IS,
      inter-individual analysis evidenced different PS reactivity; subjects which had
      the least PS during control recordings were those with the largest PS increase.
      Unlike global analysis, an inter-individual study evidenced different
      modifications of wakefulness and slow wave sleep according to individuals.
      Subjects presenting the highest amount of wakefulness in control conditions (the
      lowest amount of slow wave sleep) decreased their wakefulness amount, while
      subjects with the lowest amount of wakefulness increased it. Thus, individual
      characteristics of the sleep-wakefulness cycle should be considered while
      studying its modifications induced by different treatments.

PMID- 9147404
TI  - Effects of different perfusion medium on the extracellular basal concentration of
      dopamine in striatum and medial prefrontal cortex: a zero-net flux microdialysis
      study.
AB  - The zero-net flux microdialysis method was used to determine (1) the basal
      concentration of dopamine (DA) in the extracellular space, and (2) the in vivo
      recovery of Da in the striatum and the medial prefrontal cortex by using three
      different kinds of perfusion medium. They were, (a) commercial Ringer's solution,
      (b) low Ca2+ Ringer's solution, and (c) artificial cerebrospinal fluid (aCSF).
      Our results not only support previous findings that the high Ca2+ concentration
      in the perfusion medium could increase the baseline concentration of DA in the
      dialysate, which was collected from extracellular space through dialysis probe;
      but also provides evidence that this baseline increase was primarily due to an
      increase of basal DA concentration, and not from the increase of the in vivo
      recovery. Additionally, there was no significant difference in the basal DA
      concentration by using either commercial Ringer's solution or aCSF. This
      indicates that both commercial Ringer's solution and aCSF are suitable as good
      perfusion medium to determine the basal DA in the rat's brain.

PMID- 9147405
TI  - Abnormal distribution of neurofilament L in neurons with Alzheimer's disease.
AB  - Abnormality of cytoskeletal proteins is closely related to the pathology of
      Alzheimer's disease. As neurofilament proteins are major cytoskeletal components
      of neurons, abnormality of neurofilaments is proposed in brain with Alzheimer's
      disease. Free-floating sections of the hippocampus with Alzheimer's disease were
      studied immunohistochemically, using a polyclonal antibody specifically bound to
      the tail region of neurofilament L (NF-L). In brains with early onset type of
      Alzheimer's disease, many neurons and dystrophic neurites were labeled by the
      antibody, while these observations were not seen in either brains with late onset
      type or control brains. Double immunohistochemical staining of NF-L and tau
      protein demonstrated that abnormal deposition of NF-L was not always accompanied
      with that of tau protein, indicating that the abnormal deposition of NF-L might
      not occur in parallel with that of tau protein. These observations suggest the
      involvement of neurofilament proteins on the pathology of Alzheimer's disease in
      a different way than tau protein.

PMID- 9147406
TI  - Altered expression of delayed excitation in medial NTS neurons of spontaneously
      hypertensive rats.
AB  - The spontaneously hypertensive (SH) rat has an exaggerated sympathetic discharge
      which may result from an enhanced neuronal excitability in the central nervous
      system. To test this hypothesis, we examined the electrophysiological properties
      of neurons in the medial region of the nucleus of the solitary tract (mNTS), a
      central nucleus involved in the processing of baroreceptor afferent information,
      in SH rats and normotensive Sprague-Dawley (SD) rats. An in vitro brainstem slice
      preparation was used to record intracellularly from 18 neurons in 4-5-month-old
      SH rats and 16 neurons in 4-5-month-old SD rats. Between the two groups there was
      no significant differences in resting membrane potential, input resistance, and
      spontaneous firing frequency, or in action potential amplitude, duration, and
      after-hyperpolarization (AHP). There were no significant differences in spike
      frequency adaptation and post-tetanic hyperpolarization (PTH). Delayed excitation
      (DE), a manifestation of A-current, occurred in 88% in SH and SD mNTS neurons,
      but the duration of DE was significantly (P < 0.05) shorter in SH mNTS neurons.
      We propose that attenuated expression of A-current may contribute to increased
      sympathetic drive in SH rats.

PMID- 9147407
TI  - Elevated levels of tau-protein in cerebrospinal fluid of patients with
      Creutzfeldt-Jakob disease.
AB  - Creutzfeldt-Jakob disease (CJD) is a rare, fatal, neurodegenerative disease
      caused by a transmissible agent designated as proteinaceous infectious agent
      (prion). Searching for biochemical markers of CJD, we analysed cerebrospinal
      fluid (CSF) samples of 53 patients for tau-protein using an enzyme linked
      immunoassay (ELISA). In a group of 21 patients with definite CJD seen in the
      German case control study for CJD, tau-protein concentrations in CSF were
      significantly higher than in two control-groups of patients with other diseases
      (median 13,153 pg/ml, range 1,533-27,648 pg/ml; P = 0.0001). One group comprised
      19 patients who were seen in the same study and were diagnosed as having other
      dementing diseases (tau concentration: median 558 pg/ml, range 233-1,769 pg/ml).
      The second control group comprised 13 patients from our hospital with no
      dementing disease (tau concentration: median 296 pg/ml, range 109-640 pg/ml). We
      conclude that determination of tau protein levels in CSF is a useful marker for
      laboratory diagnosis of CJD.

PMID- 9147408
TI  - Dependence of cerebrospinal fluid Tau protein levels on apolipoprotein E4 allele
      frequency in patients with Alzheimer's disease.
AB  - Consistent pathological hallmarks of Alzheimer's disease (AD) are the formation
      of brain amyloid and neurofibrillary tangles (NFTs). Levels of the major protein
      component of NFTs, the microtubule associated protein Tau, were shown to be
      increased in cerebrospinal fluid (CSF) of AD patients as compared to age-matched
      controls. The presence of apolipoprotein E-epsilon 4 allele (APOE4) is a risk
      factor for sporadic and familial late-onset AD. ApoE may interact with the
      binding of Tau to microtubules and Tau phosphorylation in an isoform-specific
      manner. We investigated whether direct evidence of an isoform-specific
      interaction of apoE and Tau can be demonstrated in the CSF of live AD patients.
      We measured the apoE genotype and CSF levels of Tau in 19 patients with probable
      AD and 12 age-matched control subjects. We found that CSF levels of Tau increase
      with increasing APOE allele frequency (Spearman rank correlation, zeta = 2.71, P
      = 0.007). This finding may be in agreement with reports of a lesser binding of
      apoE4 to Tau, compared to apoE2 and apoE3, resulting in higher levels of unbound
      Tau in CSF.

PMID- 9147409
TI  - Evidence for tissue-associated alpha(2) macroglobulin in mouse skeletal muscle.
AB  - Alpha(2)-Macroglobulin (alpha(2)M), a major serum protease inhibitor, was
      localized in mouse skeletal muscle by immunoperoxidase histochemistry. In all
      muscles examined (mm. soleus, plantaris, and extensor digitorum longus) specific
      immunoreactivity occurred diffusely in extracellular structures (periendomysium,
      blood vessel wall) as well as inside about a half of the muscle fibers. This
      localization pattern did not change substantially by extensively perfusing deeply
      anesthetized mice with phosphate buffered saline (PBS) to remove serum alpha(2)M.
      In release experiments on fresh (nonfixed) cryostat sections, specific
      immunoreactivity persisted after an extensive prewash with PBS (up to 5-6 h), but
      a new specific staining appeared inside those fibers that were originally
      negative. Western blotting experiments were negative on the soluble fraction of
      muscle homogenate, thus confirming that the perfusion procedure was effective in
      removing serum alpha(2)M. By contrast, three specific bands (185, 165, and 35
      kDa) appeared in detergent-solubilized extracts (0.3% Triton X-100), indicating
      the occurrence of tissue-associated alpha(2)M. Confocal immunofluorescence
      microscopy revealed that the intracellular specific staining was associated to a
      longitudinal network, probably corresponding to the sarcoplasmic reticulum. A
      multifunctional role of alpha(2)M in skeletal muscle was hypothesized.

PMID- 9147410
TI  - The possible place of cathepsins and cystatins in the puzzle of Alzheimer
      disease: a review.
AB  - Lysosomal proteinases (cathepsins) and their endogenous inhibitors (cystatins)
      have been found to be closely associated with senile plaques, cerebrovascular
      amyloid deposits, and neurofibrillary tangles in Alzheimer disease (AD). Further,
      profound changes in the lysosomal system seem to be an early event in "at-risk"
      neurons of AD brains. There is an ongoing controversy as to whether lysosome
      associated proteolytic mechanisms are causally related to the development and/or
      further progression of the disease. The present article deals with some arguments
      "pro" and "contra" an involvement of the endosomal/lysosomal pathway in
      amyloidogenesis as a cardinal process in AD. Other putative targets of acidic
      proteinases and their natural inhibitors in the pathogenesis of AD (such as
      formation of neurofibrillary tangles and regulation of apolipoprotein E) are also
      discussed.

PMID- 9147411
TI  - The in vitro formation of recombinant tau polymers: effect of phosphorylation and
      glycation.
AB  - Tau Isolated from paired helical filaments, aberrant structures that appear in
      Alzheimer disease (AD) patients' brains, show at least two posttranslational
      modifications: phosphorylation (Grundke-Iqbal et al., 1986; Ihara et al., 1986)
      and glycation (Ledesma et al., 1994; Yan et al., 1994). To test whether these
      modifications could affect the capacity of tau to self-aggregate, recombinant tau
      was phosphorylated and glycated, and its capacity to form polymers analyzed. Our
      results indicate that on phosphorylation and glycation, the capacity of tau to
      form aggregates increases, and that glycation of tau could stabilize the
      assembled polymers and could facilitate formation of bundles from these polymers.

PMID- 9147412
TI  - Modifications of neuronal phosphorylated tau immunoreactivity induced by NMDA
      toxicity.
AB  - Glutamate toxicity has been involved in the pathophysiology of a large variety of
      neurodegenerative disorders. Tau Protein is a micro-tubule-associated protein
      that promotes microtubule polymerization and stabilization. Phosphorylated tau
      protein accumulates in paired helical neurofilaments, the major constituent of
      neurofibrillary tangles observed in the brain of patients suffering from
      Alzheimer disease (AD). In this study, using confocal laser microscopy and
      immunoblot analysis, we report that acute (500 mu M for 15 min) or chronic (20 mu
      M for 16 h) N-methyl-D-aspartate (NMDA) neuronal toxicities modify the
      immunoreactivity of phosphorylated tau. Neuronal degeneration produced by N
      methyl-D-aspartate is associated with an augmented immunolabeling of
      phosphorylated tau proteins at serine 202 (AT8 antibody) as observed in paired
      helical neurofilaments. This finding could help to determine the cellular
      mechanisms at the origin of neuronal degeneration associated with modifications
      of phosphorylated tau immunoreactivity produced by receptor-mediated
      extracellular signals.

PMID- 9147414
TI  - Chronic nicotine treatment prevents neuronal loss in neocortex resulting from
      nucleus basalis lesions in young adult and aged rats.
AB  - In both young adult and aged rats, we tested the ability of chronically
      administered nicotine to rescue neocortical neurons from transneuronal
      degeneration resulting 5 mo after ibotenic acid (IBO) lesioning of the nucleus
      basalis magnocellularis (NBM). Young adult (2-3 mo-old) and aged (20-22-mo-old)
      rats were given unilateral infusions of IBO (5 mu g/1 mu L) at two sites within
      the NBM. Following surgery, animals began receiving either daily ip injections of
      nicotine (0.2 mg/kg) or saline vehicle. Treatment continued for 5 mo, at which
      time all animals were sacrificed and their brains processed histologically. For
      each brain, computer-assisted image analysis was then used to analyze the
      unlesioned (left) and lesioned (right) side of five non-consecutive brain
      sections from parietal cortex Layers II-IV and V. NBM lesioning in both young
      adult and aged vehicle-treated rats resulted in a significant 16-21% neuronal
      loss ipsilateral to NBM lesioning in neocortical Layers II-IV. Aged NBM-lesioned
      rats also exhibited a significant 12% neuronal loss in neocortical Layer V
      ipsilaterally. By contrast, those NBM-lesioned young adult and aged rats that
      received daily nicotine treatment postsurgery did not show any ipsilateral
      neuronal loss in the same parietal cortex areas, indicating that chronic nicotine
      treatment prevented the transneuronal degeneration of neocortical neurons
      resulting 5 mo afer NBM lesioning.

PMID- 9147413
TI  - Nitric oxide synthase (NOS) in schizophrenia: increases in cerebellar vermis.
AB  - A high proportion of neurons in the cerebellum and in cholinergic brainstem
      nuclei stain positive for nicotinamide adenine dinucleotide phosphate-diaphorase
      (NADPHd), which is a nitric oxide synthase (NOS). Recent evidence suggests that
      schizophrenia may involve increased numbers of NADPHd-stained neurons in
      different areas of the subcortex. This led us to examine the actual concentration
      of NOS in postmortem brain specimens of cerebellum, and the relevant regions of
      brainstem tegmentum, to see if NOS concentrations were also increased in
      schizophrenia. Postmortem brain tissue was obtained at autopsy from
      schizophrenics and controls who did not have other brain disease. In patients
      with schizophrenia, NOS concentration was higher.

PMID- 9147415
TI  - Effects of valproate on amino acid and monoamine concentrations in striatum of
      audiogenic seizure-prone Balb/c mice.
AB  - The effects of valproate on CNS concentrations of gamma-aminobutyric acid (GABA),
      glulamate (GLU), glutamine (GLN); dopamine (DA), serotonin (5-HT), and
      metabolites were examined in tissue extracts of caudate nucleus of genetic
      substrains of Balb/c mice susceptible (EP) or resistant (ER) to audiogenic
      seizures. Generalized tonic-clonic seizures observed in EP mice were inhibited by
      valproate, administered 1 h prior to testing, in a dose-response fashion.
      Concentrations of GABA, GLU, and GLN, which were lower in EP mice than in ER
      mice, were significantly increased by valproate at doses of 180 and 360 mg/kg.
      Concentrations of homovanillic acid (HVA) and hydroxyindoleacetic acid (5-HIAA),
      metabolites of DA and 5-HT, were substantially increased by valproate at these
      doses. The in situ activity of tyrosine hydroxylase (TH) was not significantly
      influenced by valproate, whereas a valproate-induced increase in tryptophan
      hydroxylase (TPH) activity was observed in both striatum and in midbrain
      tegmentum. The data are consistent with the interpretation that anti-convulsive
      doses of valproate influences the intraneuronal metabolism of monoamines, GABA,
      and glutamate concurrently. Valproate's influence on the metabolism of both major
      inhibitory (GABA) and excitatory (GLY amino acids in striatum could contribute to
      its anti-convulsive effects in genetically seizure prone mice, as well as to the
      accumulation of DA and 5-HT metabolites.

PMID- 9147417
TI  - The development of resistance of HIV-1 to zalcitabine.

PMID- 9147416
TI  - Development of cytomegalovirus (CMV) disease may be predicted in HIV-infected
      patients by CMV polymerase chain reaction and the antigenemia test.
AB  - OBJECTIVE: Cytomegalovirus (CMV) is a frequent opportunistic viral pathogen in
      patients with AIDS leading to retinitis and other serious manifestations. CMV
      disease may be successfully treated. Prophylactic antiviral therapy has been
      shown to reduce the risk of CMV disease if initiated early. We evaluated PCR and
      the antigenemia tests as methods for early detection of CMV disease. METHODS: Two
      hundred HIV-seropositive subjects with CD4 T-cell counts below 100 x 10(6)/l were
      monitored with CMV polymerase chain reaction (PCR), the antigenemia test, blood
      cultures and CMV immunoglobulin (Ig) G and IgM titres every second month for 1
      year. RESULTS: Thirty-eight patients (19%) developed CMV disease. The PCR test
      detected CMV DNA a median of 46 days before onset of disease. This was earlier
      than the median of 34 for the antigenemia test and a median of 1 day for CMV
      blood cultures. Univariate analysis showed that the CMV PCR, the antigenemia test
      and blood cultures all had significant predictive values for subsequent
      development of CMV disease with odds ratios (OR) of 30, 22 and 20. CMV serology
      had no predictive value. Multivariate analysis showed that the PCR method was
      superior to the other tests; OR: CMV PCR 10.0, antigenemia test 4.4 and CMV
      cultures 4.3. No clinical parameters had any significant predictive value in the
      stepwise multivariate model. CONCLUSIONS: The CMV PCR and the CMV antigenemia
      tests are both sensitive methods that may predict development of CMV disease up
      to several months prior to clinical disease. These methods make it possible to
      select patients at high risk for CMV disease and suitable for prophylactic
      therapy against CMV.

PMID- 9147418
TI  - CD4+ T-cell recognition of diverse clade B HIV-1 isolates.
AB  - OBJECTIVES: To evaluate the effect of sequence variation within the gp120 V3 loop
      on CD4 T-cell recognition. DESIGN: CD4 T-cell clones were generated using
      synthetic peptides to circumvent the difficulties of using polyclonal T-cell
      responses. Peptides based on other HIV isolates were then used to determined the
      influence of single and multiple sequence differences. RESULTS: Three of the
      panels of T-lymphocyte clones (TLC), which were all specific to diverse HIV-1
      clade B gp120 V3-loop peptides differing in a limited number of residues, had
      heterogeneous patterns of response to peptides differing in length and sequence
      indicating that they recognized distinct but overlapping epitopes. The panels of
      TLC also differed in the extent to which they tolerated sequence differences
      between cell-culture-adapted or primary HIV-1 isolates. One panel responded to
      peptides based on several clade B and one clade D isolate. In contrast, two
      panels, generated from two different donors using the same peptide, only
      responded to a limited number of clade B isolates, whereas another only
      recognized HIV-1BRU. Two of the panels were also stimulated by peptides based on
      clinical isolates from one patient with some sequence changes enhancing T-cell
      recognition. CONCLUSIONS: These data are consistent with highly diverse CD4 T
      cell recognition of the HIV-1 gp120 V3 loop, which is influenced by the sequence
      differences within the T-cell epitopic region and has implications for the
      pathogenesis and design of vaccines against HIV-1.

PMID- 9147419
TI  - Cerebral proton magnetic resonance spectroscopy in asymptomatic HIV infection.
AB  - OBJECTIVE: To determine whether proton magnetic resonance spectroscopy (MRS)
      demonstrates central nervous system abnormalities in asymptomatic HIV-1-infected
      individuals. DESIGN: Both prospective and retrospective cross-sectional analyses
      of MRS in asymptomatic HIV-infected individuals. SETTING: Two specialists
      HIV/AIDS outpatient facilities in London. PARTICIPANTS: Eighty-four HIV-1
      seropositive asymptomatic men; 29 HIV-1 antibody-negative homosexual men at high
      risk for HIV infection and 48 HIV-1 antibody-negative men at low-risk for HIV
      infection as controls. MAIN OUTCOME MEASURES: Single voxel, gradient-localized
      proton MRS performed at 1.5 T with 135 msec echo-time and 1,600 msec repeat-time
      in an 8 ml volume of interest positioned in the parieto-occipital white matter.
      Spectroscopic results were expressed as ratios between the areas under the N
      acetyl (NA), creatine (Cr) and choline (Cho) resonance peaks. RESULTS: There were
      no differences between those controls at high and those at low-risk for HIV
      infection. Comparing the combined control groups with the asymptomatic
      seropositive patients there were statistically significant differences in NA/Cho,
      NA/Cr (both P < 0.05) and NA/(NA + Cho + Cr) (P < 0.01). CONCLUSION:
      Abnormalities in cerebral biochemistry may be demonstrated by proton MRS during
      asymptomatic HIV-1 infection.

PMID- 9147420
TI  - TAR and Sp1-independent transactivation of HIV long terminal repeat by the Tat
      protein in the presence of human cytomegalovirus IE1/IE2.
AB  - OBJECTIVE: The HIV Tat protein is a transcriptional transactivator of the HIV-1
      long terminal repeat (LTR) promoter element. Its activity depends on its direct
      interaction with the trans-activation response (TAR) element, although TAR
      independent activation by Tat has been demonstrated in different cells.
      Herpesviruses in general and human cytomegalovirus (HCMV) in particular are often
      isolated from HIV-1-infected patients and could play a role in the activation of
      latent HIV and in a subsequent increase in HIV replication. HCMV immediate early
      gene products (IE1 and IE2) are nuclear phosphoproteins that play a pivotal role
      in HCMV replication and have been shown to transregulate both viral and cellular
      gene expression. It has repeatedly been shown that HCMV IE1/IE2 can independently
      transactivate HIV-1 LTR. The aim of this study was to investigate IE1/IE2
      transactivation of HIV-1 LTR in a CD4+ T-cell line in the absence and presence of
      HIV-1 Tat to establish whether IE1/IE2 can synergize with Tat. METHODS: HIV-1 LTR
      transactivation by HCMV IE1/IE2 in the presence and absence of HIV-1 Tat was
      determined by transient transfection experiments of J-Jhan lymphoblastoid cells
      with a series of different expression vectors. RESULTS: We found a strong
      synergistic transactivation between HIV Tat and the IE1-IE2 complex on HIV LTR
      activity using vectors driven either by wild-type LTR or by the nuclear factor NF
      kappa(B) response element-mutated HIV LTR. IE1/IE2 synergism with HIV Tat was
      also observed in Sp1 binding site-mutated for TAR-deleted LTR, which cannot be
      activated by Tat alone. This cooperation is abolished when the region in IE2 that
      binds the TATA box binding protein is deleted. CONCLUSIONS: The results obtained
      indicate that Sp1-binding and TAR sequences are not strictly required for Tat
      responsiveness when Tat is directed to the HIV promoter by HCMV IE1-IE2. This
      synergistic effect is mediated by the IE2 and TATA-binding region, and could play
      a major role in HIV activation when cells are infected by both viruses, a feature
      often observed in AIDS patients.

PMID- 9147421
TI  - Heterozygosity for a deletion in the CKR-5 gene leads to prolonged AIDS-free
      survival and slower CD4 T-cell decline in a cohort of HIV-seropositive
      individuals.
AB  - OBJECTIVE: Recently, it has been shown that a homozygous 32 base-pair deletion in
      the gene encoding CKR-5, a major coreceptor for HIV-1, leads to resistance to
      infection with HIV-1. We have investigated whether HIV-seropositive individuals
      who were heterozygous for the CKR-5 deletion had a different course of the
      disease. DESIGN: Thirty-five high-risk HIV-seronegative and 99 HIV-seropositive
      Danish homosexual men followed form 1985 to 1996 and 37 blood donors were
      analysed for their CKR-5 genotype by polymerase chain reaction. RESULTS: Two (6%)
      of the 35 HIV-seropositive subjects at high-risk of infection were homozygous and
      seven (20%) were heterozygous for the CKR-5 deletion. This was not significantly
      different from the distribution in normal donors. Twenty-two (22%) of the 99 HIV
      seropositive subjects were heterozygous and none was homozygous. Two subgroups of
      patients who had an opposite course of the HIV disease were identified. Of nine
      long-term non-progressors, six (66%) were heterozygous for the deletion. This
      frequency is significantly higher than in nine rapid progressors of whom non was
      heterozygous. The frequency of heterozygotes in long-term non-progressors was
      also significantly higher than in the cohort as a whole. A Kaplan-Meier plot of
      the HIV-seropositive subjects, of whom 57 developed AIDS, showed a significantly
      better prognosis within the first 7 years of follow-up for those who were
      heterozygous for the deletion. Heterozygous individuals also had a significantly
      slower decrease in CD4 T-cell count per year. CONCLUSION: Individuals who are
      heterozygous for the 32-base-pair deletion in the CKR-5 gene have a slower
      decrease in their CD4 T-cell count and a longer AIDS-free survival than
      individuals with the wild-type gene for up to 11 years of follow-up.

PMID- 9147422
TI  - Clarithromycin and ethambutol with or without clofazimine for the treatment of
      bacteremic Mycobacterium avium complex disease in patients with HIV infection.
AB  - OBJECTIVE: To compare the efficacy of two- and three-drug regimens for treating
      Mycobacterium avium complex (MAC) bacteremia in patients with AIDS. DESIGN:
      Randomized open-label clinical trial. SETTING: Outpatient HIV specialty centers'
      clinics. PATIENTS: A total of 106 adults with AIDS and MAC bacteremia.
      INTERVENTIONS: Patients were treated with clarithromycin 500 mg twice daily and
      ethambutol 800-1,000 mg daily and were randomized to receive clofazimine 100 mg
      daily or no clofazimine. MAIN OUTCOME MEASURES: Quantitative blood MAC cultures,
      symptoms, adverse reactions and survival. RESULTS: Patients randomly assigned to
      three drugs had significantly higher baseline colony counts of MAC in blood than
      patients receiving two drugs. The proportion of patients becoming culture
      negative was 65% in the two-drug group and 54% in the three-drug group. The
      median time to negative culture was 58 days for patients in the two-drug and 63
      days for the three-drug group. At the last visit during treatment, the mean
      reduction in colony forming units/ml of MAC in blood was 1.8 log10 for the two
      drug group and 2.3 log10 for the three-drug group. Improvement in fever and night
      sweats was reported by 87 and 89% of the two-drug patients and 84 and 86% of the
      three-drug patients. During the study, 38% of two-drug patients and 61% of three
      drug patients died (P = 0.032), and time to death was shorter in patients treated
      with three drugs (P = 0.012). In a multivariate analysis, both assignment to
      clofazimine and high baseline colony counts of MAC bacteremia were significantly
      associated with death (P < 0.05). CONCLUSION: The addition of clofazimine to a
      regimen of clarithromycin and ethambutol for MAC bacteremia in AIDS patients does
      not contribute to clinical response and is associated with higher mortality.

PMID- 9147423
TI  - Clinical features and outcomes of HIV-related cytomegalovirus pneumonia.
AB  - OBJECTIVE: To describe the characteristics and outcomes of HIV-infected patients
      with biopsy-proven cytomegalovirus (CMV) pneumonia. DESIGN: Retrospective study.
      SETTING: A 900-bed acute facility in New York City. PATIENTS: Eighteen HIV
      infected patients with pathologically confirmed CMV inclusions in lung tissue
      without other pathogens and 36 control patients with biopsy-proven Pneumocystis
      carinii pneumonia (PCP) selected for comparisons by computer-generated random
      sequential numbers. MAIN OUTCOME MEASURES: Demographic, clinical, laboratory,
      radiological findings, and in-hospital mortality. RESULTS: Eighteen HIV-infected
      patients were found to have CMV lung infection alone. Pathologic findings were
      pneumonitis (n = 11); pneumonitis and pulmonary vasculitis (n = 1); and CMV
      inclusions alone (n = 6). All presented with respiratory symptoms (cough or
      dyspnea), 89% had fever, 83% had radiological abnormalities, and 56% had severe
      hypoxemia. The pulmonary presentation was similar except for higher lactate
      dehydrogenase (median, 449 versus 329 IU/l; P = 0.03) and presence of pleural
      effusions (33 versus 0%; P = 0.001) in CMV patients. Multivariate analysis showed
      that CD4 counts < or = 12 x 10(6)/l (odds ratio; 9.2; P = 0.029) and
      extrapulmonary CMV (odds ratio, 20.4; P = 0.039) were independently associated
      with CMV pneumonia. Seventeen patients received specific anti-CMV therapy for a
      mean of 22 +/- 13 days. In-hospital mortality was higher in patients with CMV
      pneumonia (odds ratio, 11.9; P = 0.002). The median time from admission to death
      was 31 days. CONCLUSIONS: CMV lung infection was seen in severely
      immunosuppressed HIV-positive patients and associated with clinical pneumonitis
      with high early mortality. Although the clinical features resemble PCP, the
      presence of extrapulmonary CMV disease should suggest the diagnosis of CMV
      pneumonia.

PMID- 9147424
TI  - Vitamin A deficiency and maternal-infant transmissions of HIV in two metropolitan
      areas in the United States.
AB  - OBJECTIVE: To determine whether vitamin A deficiency is associated with maternal
      infant HIV transmission among HIV-infected pregnant women in two United States
      cities. METHODS: Third trimester serum vitamin A levels were evaluated using high
      performance liquid chromatography in 133 HIV-infected women who delivered
      livebirths during May 1986 to May 1994 and whose infants had known HIV infection
      status. RESULTS: Sixteen per cent (seven out of 44) of the transmitting mothers
      and 6% (five out of 89) of the non-transmitting mothers had severe vitamin A
      deficiency (< 0.70 mumol/l; P = 0.05). Maternal-infant transmission was also
      associated with prematurity < 37 weeks gestation (P = 0.02), and Cesarean section
      delivery (P = 0.04), CD4 percentage (P = 0.03) and marginally associated with
      duration of membrane rupture of > or = 4 h (P = 0.06) by univariate analysis. In
      a multivariate logistic regression model, severe vitamin A deficiency [adjusted
      odds ratio (AOR), 5.05; 95% confidence interval (CI), 1.20-21.24], Cesarean
      section delivery (AOR, 3.75; 95% CI, 1.10-12.87), and prematurity (AOR, 2.25; 95%
      CI, 1.22-4.13) were associated with transmission after adjusting for CD4+
      percentage, and duration of membrane rupture. CONCLUSION: Increased risk of
      maternal-infant transmission was associated with severe vitamin A deficiency
      among non-breastfeeding women in these cohorts from the United States.

PMID- 9147425
TI  - Pregnancy and contraception in a French cohort of HIV-infected women. SEROCO
      Study Group.
AB  - OBJECTIVE: To describe the impact of HIV diagnosis on contraception, incidence of
      pregnancy and live-births among HIV-infected women in France. DESIGN: Follow-up
      of women included in a French cohort of HIV-infected adults (SEROCO). METHODS: In
      17 hospital-based units and one private practitioners' network in the Paris area
      and south-east region of France, 412 HIV-infected women (volunteers) were
      enrolled from 1988 to 1993, shortly after HIV diagnosis (median, 3 months), and
      followed for a median of 3 years. The main outcome measures were incidence and
      outcome of pregnancy, proportions of women sexually active and methods of
      contraception. RESULTS: The incidence of pregnancy decreased significantly from
      20.4 per 100 person-years in the year preceding HIV diagnosis to 7.9 per 100
      person-years after HIV diagnosis (P < 0.001), whereas the proportion of
      pregnancies voluntarily interrupted doubled (63 versus 29%). The proportion of
      women who were sexually inactive increased from 5% before HIV diagnosis to 20%
      thereafter. During followup, 80% of sexually active women were using
      contraceptive methods. CONCLUSIONS: The study supports an association between the
      discovery of HIV infection and a decrease in the proportion of women who are
      sexually active, a decrease in the incidence of pregnancy in general and live
      births in particular, and an increase in the proportion of pregnancies
      voluntarily interrupted. Nevertheless, 24% of the women became pregnant and
      around 20% of sexually active women were not using any contraception. The high
      rate of voluntary abortion may indicate that many of these pregnancies were
      unplanned and could have been prevented.

PMID- 9147426
TI  - The HIV epidemic in Zambia: socio-demographic prevalence patterns and indications
      of trends among childbearing women.
AB  - OBJECTIVE: To examine socio-demographic HIV prevalence patterns and trends among
      childbearing women in Zambia. DESIGN: Repeated cross-sectional surveys. METHODS:
      Personal interviews and unlinked anonymous testing of blood samples of women
      attending antenatal care in selected areas. RESULTS: The 1994 data includes
      information from 27 areas and a total of 11,517 women. The HIV prevalence among
      urban residents appeared with moderate variation at a very high level (range 25
      32%, comparing provinces). The geographical variation was more prominent in rural
      populations (range 8-16%) and was approximately half the prevalence level of the
      urban populations. With the exception of the 15-19 years age-group, HIV infection
      was found to rise sharply with increasing educational attainment (odds ratio,
      3.1; confidence interval, 2.6-3.8) when contrasting extreme educational levels.
      Although the assessment of trends is somewhat restricted, the available
      information indicates stable prevalence levels in most populations over the last
      2-4 years. CONCLUSIONS: The data showed extremely high HIV prevalence levels
      among childbearing women. Longer time-intervals between surveys are needed,
      however, in order to verify the stability in prevalence identified by this study.
      The tendency to changing differentials by social status is suggested as a
      possible sign of an ongoing process of significant behavioural change.

PMID- 9147427
TI  - Cost-effectiveness of HIV-prevention skills training for men who have sex with
      men.
AB  - OBJECTIVE: A previous study empirically compared the effects of two HIV
      prevention interventions for men who have sex with men: (i) a safer sex lecture,
      and (ii) the same lecture coupled with a 1.5 h skills-training group session. The
      skills-training intervention led to a significant increase in condom use at 12
      month follow-up, compared with the lecture-only condition. The current study
      retrospectively assesses the incremental cost-effectiveness of skills training to
      determine whether it is worth the extra cost to add this component to an HIV
      prevention intervention that would otherwise consist of a safer sex lecture only.
      DESIGN: Standard techniques of incremental cost-utility analysis were employed.
      METHODS: A societal perspective and a 5% discount rate were used. Cost categories
      assessed included: staff salary, fringe benefits, quality assurance, session
      materials, client transportation, client time valuation, and costs shared with
      other programs. A Bernoulli-process model of HIV transmission was used to
      estimate the number of HIV infections averted by the skills-training intervention
      component. For each infection averted, the discounted medical costs and quality
      adjusted life years (QALY) saved were estimated. One- and multi-way sensitivity
      analyses were performed to assess the robustness of base-case results to changes
      in modeling assumptions. RESULTS: Under base-case assumptions, the incremental
      cost of the skills training was less than $13,000 (or about $40 per person). The
      discounted medical costs averted by incrementally preventing HIV infections were
      over $170,000; more than 21 discounted QALY were saved. The cost per QALY saved
      was negative, indicating cost-savings. These results are robust to changes in
      most modeling assumptions. However, the model is moderately sensitive to changes
      in the per-contact risk of HIV transmission. CONCLUSIONS: Under most reasonable
      assumptions, the incremental costs of the skills training were outweighed by the
      medical costs saved. Thus, not only is skills training effective in reducing
      risky behavior, it is also cost-saving.

PMID- 9147428
TI  - Sexually transmitted disease (STD) and HIV risk in heterosexual adults attending
      a public STD clinic: evaluation of a randomized controlled behavioral risk
      reduction intervention trial.
AB  - OBJECTIVE: To evaluate the efficacy of a cognitive/behavioral skills-building
      intervention to prevent sexually transmitted diseases (STD) in high-risk
      heterosexual adults. DESIGN: A randomized controlled trial with assessments at
      baseline, and at 3 and 5 months. SETTING: San Francisco STD Clinic. PATIENTS: A
      total of 399 patients were randomly assigned to a four-session, individual, multi
      component, cognitive/behavioral intervention (n = 199), or a brief standardized
      counseling session offered to all patients (n = 200). INTERVENTION: Based on the
      AIDS Risk-Reduction Model, the aims of the intervention were to increase
      prevention knowledge, reduce high-risk psychosocial factors, and build decision
      making and communication skills to modify sexual behaviors. MAIN OUTCOME
      MEASURES: The primary outcome of interest was STD. The secondary outcome was
      number of risky sexual activities. RESULTS: There were no differences between the
      intervention (13%) and control (11%) groups in their acquisition of STD. Among
      men, condom use increased more at 3 months in the intervention group than the
      control group (56.8 versus 42.3%; P < 0.05). In addition, the mean number of
      sexual partners without condom use was lower in the intervention group than in
      the control group at 5 months (0.6 versus 0.9; P < 0.01). CONCLUSIONS: The
      results suggest that a cognitive/behavioral, skills-building intervention
      consisting of individual, multiple sessions and follow-up assessments can be
      implemented and evaluated with high-risk heterosexually active adults attending
      public STD clinics. Our intervention did not have a significant impact on STD,
      although it had some impact on behavior in men, but not in women.

PMID- 9147429
TI  - Field evaluation of rapid HIV serologic tests for screening and confirming HIV-1
      infection in Honduras.
AB  - OBJECTIVE: To determine the ability of simple, rapid tests to identify HIV-1
      antibody-positive specimens in field settings using the World Health
      Organization's (WHO) alternative testing strategies. DESIGN: Three-phase
      evaluation of simple, rapid assays using banked specimens and prospectively
      collected serum specimens at regional hospitals and rural clinics. METHODS: Seven
      test (Retrocell, Genie, HIVCHEK, SUDS HIV-1, Testpack, Serodia HIV-1, and HIV-1/2
      RTD) were evaluated and results compared with standard enzyme immunoassay (EIA)
      and Western blot results (phase 1). Further evaluation consisted of prospective
      testing of routine specimens at regional (phase 2; n = 900) and rural, peripheral
      laboratories (phase 3; n = 1266) throughout Honduras with selected assays.
      RESULTS: Sensitivity and specificity were calculated for each assay and
      combination of assays for each phase to evaluate the effectiveness of the WHO
      alternative testing strategies. All tests in all phases were > 99% sensitive
      after correcting for technical errors, with two exceptions (SUDS, phase 1;
      HIVCHEK, phase 3). In phase 3, where the testing algorithm was diagnostic,
      several combinations of assays were 100% sensitive and specific using WHO
      strategy II or III. For the Honduras Ministry of Health, the combination of
      Retrocell and Genie was found to be equally sensitive, more specific (no
      indeterminate results), and less expensive than EIA/Western blot. CONCLUSION:
      Combinations of rapid, simple HIV antibody assays provide sensitivity and
      specificity performance comparable to EIA/Western blot. Application of these
      combinations in the WHO alternative testing strategies provides an inexpensive
      and effective method of determining HIV status. Assay combinations using these
      strategies can be easily performed in small, rural laboratories and have been
      implemented in routine HIV screening in Honduras.

PMID- 9147430
TI  - On-site HIV testing in resource-poor settings: is one rapid test enough?
AB  - OBJECTIVE: To determine the feasibility, accuracy and cost-effectiveness of a
      rapid, on-site, HIV testing strategy in a rural hospital, and to assess its
      impact on test turnaround time and the proportion of patients post-test
      counselled. DESIGN: Prospective comparison of two testing strategies [double
      rapid test on-site versus central enzyme-linked immunosorbent assay (ELISA)-based
      testing], and an economic evaluation. SETTING: Hlabisa Hospital, a rural South
      African district hospital. PATIENTS: A total of 454 consecutive adult inpatients
      requiring and consenting to HIV testing as part of their clinical management.
      MAIN OUTCOME MEASURES: Concordance between rapid tests, and between the rapid and
      ELISA strategies, test turnaround time, proportion of patients post-test
      counselled, and cost-effectiveness. RESULTS: HIV seroprevalence was 49.6%. Both
      rapid tests were concordant in all patients [one-sided 95% confidence interval
      (CI) of probability, 99.3-100]. The rapid strategy was 100% sensitive (95% CI,
      97.9-100) and 99.6% specific (95% CI, 97.2-100) compared with the ELISA strategy.
      The mean interval between ordering a test and post-test counselling fell from 21
      days prior to the introduction of the rapid test strategy to 4.6 days after its
      introduction (P < 0.00001). The proportion of patients post-test counselled
      increased to 96% from 17% after the introduction of the rapid test strategy (P <
      0.00001). By using a double rapid test strategy the cost per patient post-test
      counselled was almost halved to US$ 11. Accuracy of the rapid strategy was not
      substantially increased by performing two tests. CONCLUSION: In high prevalence,
      resource-poor settings, rapid, on-site HIV testing is feasible, accurate and
      highly cost-effective, substantially increasing the number of patients post-test
      counselled. A single rapid test may be sufficient.

PMID- 9147431
TI  - Elevated interferon-alpha in maternal and umbilical cord blood and in the
      placental trophoblast suggests natural protection against vertical transmission
      of HIV-1 in a Kenyan cohort.

PMID- 9147432
TI  - Disseminated microsporidiosis in AIDS: are any organs spared?

PMID- 9147433
TI  - Comparison of fluorescence and standard light microscopy for diagnosis of
      microsporidia in stools of patients with AIDS and chronic diarrhoea.

PMID- 9147434
TI  - Human chorionic gonadotrophin in the treatment of HIV-related Kaposi's sarcoma.

PMID- 9147435
TI  - Unusual occurrence of spontaneous haematomas in three asymptomatic HIV-infected
      haemophilia patients a few days after the onset of ritonavir treatment.

PMID- 9147436
TI  - HIV-1 subtypes A and B isolated from the Republic of Korea.

PMID- 9147437
TI  - Short-term response to indinavir in patients with advanced HIV disease with prior
      heavy exposure to nucleoside analogues.

PMID- 9147438
TI  - The efficacy of nonoxynol-9 from an in vivo point of view.

PMID- 9147439
TI  - Strongyloides stercoralis hyperinfection diagnosed by gastric cytology in an AIDS
      patient.

PMID- 9147440
TI  - Evidence for the selective pressure to reduce heterogeneity of HIV-1 subtype E
      envelope V3-loop sequences in an intrafamilial infection case.

PMID- 9147441
TI  - Re-evaluation of time to progression of foscarnet salvage therapy for
      cytomegalovirus retinitis in AIDS patients clinically resistant to ganciclovir.

PMID- 9147442
TI  - Response of HIV-associated thrombocytopenia to triple agent antiretroviral
      therapy.

PMID- 9147443
TI  - Relapses of chronic hepatitis C in HIV-infected patients who responded to
      interferon therapy. Hepatitis/HIV Spanish Study Group.

PMID- 9147444
TI  - HIV infection in Madagascar in 1995.

PMID- 9147445
TI  - Male circumcision and susceptibility to HIV infection among men in Tanzania.
AB  - BACKGROUND: Evidence from ecological studies and from studies of and sexually
      transmitted disease (STD) patients in sub-Saharan Africa suggests that there is a
      protective effect of male circumcision against HIV infection. There are, however,
      few population-based studies that have controlled adequately for potential
      confounding factors. METHODS: Data from the five population-based studies in
      north-western Tanzania were used to investigate the association between male
      circumcision and the risk of HIV infection and STD. The effects of circumcision
      on HIV prevalence, syphilis (positive Treponema pallidum haemagglutination; TPHA)
      and self-reported STD were analysed, controlling for a range of demographic and
      sociocultural variables, and indicators of sexual behaviour. RESULTS: In north
      western Tanzania, circumcision was previously restricted to Muslims and specific
      ethnic groups, but is now more widespread, particularly in urban ares and among
      more educated men. Assessment of the reliability and validity of self-reported
      circumcision status showed that these data could be considered fairly accurate,
      although there was some tendency for circumcision to be over-reported. On
      univariate analysis, circumcision status was unrelated to HIV prevalence in most
      studies. After controlling for confounding variables, however, there was a modest
      but significant reduction of the HIV prevalence among circumcised men [odds ratio
      (OR), 0.62; 95% confidence interval (CI), 0.48-.81]. This effect appeared
      stronger in urban areas (OR, 0.46; 95% CI, 0.32-0.68) and roadside villages (OR,
      0.65; 95% CI, 0.42-1.01) than in rural areas and islands (OR, 1.00 and 1.01
      respectively). There was no association between circumcision status and syphilis
      serology (TPHA), but there was a positive association between circumcision and
      self-reported STD, although this was not significant after adjustment for
      confounding variables. CONCLUSION: Male circumcision has a protective effect
      against HIV infection in this population, which may be stronger in urban areas
      and roadside settlements than in the rural areas. Ethnic group and religious
      denomination are no longer the sole determinants of male circumcision.

PMID- 9147446
TI  - Systematic improvement of a chemically-defined protein-free medium for hybridoma
      growth and monoclonal antibody production.
AB  - A chemically-defined protein-free medium (FMX-Turbodoma) has been improved for
      the production of monoclonal IgA antibodies by hybridoma cells, using a
      systematic method. Cell growth rate, IgA production, activity and molecular
      weight pattern have been used as optimization criteria. Of potentially important
      supplements, glucose, glutamine, Pluronic acid F-68 as well as several amino
      acids had significant beneficial effects. A determination of amino acids profiles
      via HPLC analysis allowed the formulation of a balanced medium. Unbalanced
      supplementations of amino acids were found undesirable because of the toxicity of
      some amino acids at high concentration. Compared with the basal medium, the
      maximum viable cell and final IgA concentrations in the final version of the
      protein-free medium were increased by 130% and 700%, respectively, whereas the
      IgA molecular weight pattern and in vitro activity were not affected. The IgA
      production was even higher than in a serum-containing medium (RPMI 1640 + 10%
      FCS) and the price of the protein-free medium is about 20% of this serum
      containing medium. This makes such a protein-free medium very convenient for
      laboratory and large-scale production.

PMID- 9147447
TI  - Formation and cell-medium partitioning of autoinhibitory free fatty acids and
      cyclodextrin's effect in the cultivation of Bordetella pertussis.
AB  - Palmitic, palmitoleic and stearic acids were found in the extracted cellular
      lipids of virulent Bordetella pertussis as unesterified acids in confirmation of
      earlier taxonomic analyses. The same free fatty acids (FFAs) were found in the
      spent culture supernatant in concentrations higher than in the uninoculated
      medium, indicating that they are released into the extracellular medium. These
      long-chain fatty acids are known to inhibit the growth of B. pertussis at
      concentrations as low as 1 ppm. Measurement of palmitate cell-medium partitioning
      demonstrated a strong tendency of FFAs for cellular adsorption. Inhibition
      kinetics indicated that the cell-bound FFA was responsible for inhibition and
      that the specific cellular FFA concentrations actually found during growth were
      similar to those determined to be inhibitory. Autoinhibition by these endogenous
      FFAs provides an explanation of the low maximum cell concentrations currently
      attainable in liquid media. Addition of soluble dimethyl-beta-cyclodextrin
      (MebetaCD) to FFA-inhibited cultures resulted in a rapid reversal of the
      inhibition. A corresponding shift in the distribution of FFAs from the cells to
      the extracellular medium demonstrated that MebetaCD sequesters FFAs. Although
      MebetaCD did not increase final cell concentrations and even had an adverse
      effect on growth at concentrations above 1 g l-1, it did (at 1 g l-1 extend the
      initial period of high growth rate leading to shorter cultivation times.

PMID- 9147448
TI  - Growth energetics and metabolic fluxes in continuous cultures of Penicillium
      chrysogenum.
AB  - Continuous cultures of the penicillin producing fungus Penicillium chrysogenum
      have been analyzed with respect to the macromolecular composition of the
      mycelium. All cultivations were carried out using a chemically defined medium
      with glucose as the growth limiting component. Biomass was harvested at steady
      state and analyzed for proteins, lipids, RNA, DNA, and carbohydrates.
      Carbohydrates present in the cell wall, i.e., glucans and chitin, and
      carbohydrates serving as storage materials, i.e., glycogen, were measured. It was
      observed that the levels of DNA and lipids are relative constant, whereas the
      proteins and stable RNA levels increase with the specific growth rate and the
      total amount of carbohydrates decreases with the specific growth rate. Glycogen
      is only present in small amounts, decreasing with the specific growth rate. As an
      average the measured macromolecules account for 77 +/- 2% (w/w) of the biomass.
      On the basis of estimations of the metabolic costs for biosynthesis and
      polymerization of the different macromolecules the total ATP and NADPH
      requirements for cell biosynthesis from glucose and inorganic salts, i.e.,
      YxATP,growth and YxNADPH, have been quantified. The biosynthesis of 1 g biomass
      was calculated to require 39.9 mmol of ATP and 7.5 mmol of NADPH when cytosolic
      acetyl-CoA is formed from citrate by citrate lyase and oxaloacetate is recycled
      back into the TCA cycle. Other pathways of acetyl-CoA biosynthesis have been
      considered. The calculations show that the different biosynthetic routes for
      generating cytosolic acetyl-CoA have a significant influence on the theoretical
      value of ATP and NADPH requirements for cell biosynthesis. Combining a detailed
      stoichiometric model for growth and product formation of P. chrysogenum with
      experimental data on the macromolecular composition of P. chrysogenum and precise
      measurements of substrate uptake and product formation the intracellular flux
      distribution was calculated for different cultivation conditions.

PMID- 9147449
TI  - Enzyme-catalysed carbon-carbon bond formation: large-scale production of
      Escherichia coli transketolase.
AB  - Escherichia coli strain JM107/pQR700 possesses the vector pBGS18, a high copy
      number plasmid carrying kanamycin resistance, into which a 4.4 kb fragment
      containing the transketolase gene had been cloned. The bacterium was grown at 20
      and 1000 1 scale for the production of transketolase. The specific growth rate
      was maintained at 0.15 h-1 until the bacterial concentration reached 20 g dry wt
      per litre at which point the culture was harvested. The clarified cell extract
      obtained after disruption of the bacteria in a high-pressure homogeniser
      contained about 230 U ml-1 of the enzyme, which represented about 40% of the
      total protein released. No further purification was done at large scale as the
      clarified cell extract could be used satisfactorily for biotransformations.

PMID- 9147450
TI  - [The new editors' message].

PMID- 9147451
TI  - [Anesthetic agents and visual evoked potentials in patients undergoing
      transphenoidal or breast reconstruction surgery].
AB  - To study the effect of general anesthesia with diazepam, fentanyl and nitric
      oxide, a common combination during the intraoperative recording of visual evoked
      potentials (VEP) in transsphenoidal surgery, we compared the amplitude and
      latency of VEP components before anesthesia and at four moments after induction
      during the first hour of elective breast surgery in 20 patients with no
      neurological deficits. The results for these patients (group I) before anesthesia
      and 15 min after induction were also compared to presurgical recordings for 19
      patients with hypophysial tumors and histories visual field and acuity
      involvement (group II). Latency increased significantly as a result of anesthesia
      whereas amplitude was affected to a lesser degree. Changes in latency of the main
      positive component was after anesthesia was the only parameter that was
      significantly different for the two group studied, variation being greater in
      group II.

PMID- 9147452
TI  - [Assessing quality of life in Parkinson's disease using the PDQ-39. A pilot
      study].
AB  - The aim of this pilot study was to analyze an adaptation of the PDQ-39, a
      Parkinson's disease (PD) quality of life questionnaire, for use in Spanish. Fifty
      patients were enrolled. Patient characteristics and medical histories were
      recorded, including scores on the following scales: Hoehn and Yahr (HY), PD
      unified (UPDRS), Schwab and England (SE), Intermediate Scale for Assessment of PD
      (ISAPD). Barthel Index (BI), Pfeiffer's SPMSQ, Global Deterioration Scale (GDS),
      Geriatric Depression Scale (GDS). Hospital Depression and Anxiety Scale (HDA) and
      the PDQ-39. Descriptive statistics were recorded, as well as Spearman's r and
      ANOVA results. The dimensions that correlated well with PD scale scores were
      mobility, daily life activities and cognitive deterioration. The dimension stigma
      correlated with complications on the UPDRS and the ISAPD. Emotional well-being
      correlated with subscale I of the UPDRS, the GDS and the HDA (r = 0.39-0.79, p <
      0.01-0.001). Physical discomfort correlated only with depression and anxiety.
      Stage of disease and level of depression influenced most dimensions assessed by
      the PDQ-39. Some psychosocial factors that are important components of well-being
      are scarcely reflected by the clinical scales usually applied.

PMID- 9147453
TI  - [Normalization of cognitive and functional assessment instruments for dementia
      (NORMACODEM) (I): objectives, content and population].
AB  - To adequately evaluate patients with 4 neuropsychological deficits a project for
      norming cognitive and functional instruments that assess dementia (NORMACODEM)
      was designed. Four hundred fifty-one subjects in three groups: 254 controls, 86
      patients with minor memory/cognitive deficits without dementia (DWD) and 111
      patients with probable Alzheimer-type dementia (ATD) according to the
      NINCDS/ADRDA criteria. Mini-Mental State Examination (MMSE), Alzheimer's Disease
      Assessment Scale (ADAS), Abbreviated Barcelona Test (ABT), Global Dementia
      Staging (GDS), Functional Assessment Staging (FAST), Clinical Dementia Rating
      (CDR), Rapid Disability Rating Scale-2 (RDRS-2), Blessed Dementia Rating Scale
      (BDRS), Interview for Deterioration in Daily life in Dementia (IDDD), Geriatric
      Evaluation by Relatives Rating Instrument (GERRI), Geriatric Depression Scale
      (GDS), Zung Self-Rating Anxiety Scale (ZSRAS). Descriptive statistics and
      analysis of variance. The characteristics of the sample were as follows.
      CONTROLS: 99 men, 155 women. Mean (SD) age: 64.6 (10.9) years. Mean (SD)
      educational level: 9.1 (4.9) years. DWD: 42 men, 44 women. Mean (SD) age: 65.8
      (8.7) years. Men (SD) educational level: 8.4 (4.4) years. ATD: 48 mean, 63 women.
      Mean (SD) age: 68.3 (8.0) years. Mean (SD) educational level: 6.2 (4.3) years.
      The ATD patients were significantly older than the controls. Mean educational
      level was significantly lower in the ATD group than in the other two.

PMID- 9147454
TI  - [Adaptation and normalization of the Alzheimer's disease Assessment Scale for
      Spain (NORMACODEM) (II)].
AB  - This report is part of a project for norming cognitive and functional instruments
      that assess dementia (NORMACODEM). To adapt and norm the Alzheimer's Disease
      Assessment Scale (ADAS) for use in Spain. Two hundred fifty-four controls, 86
      patients with minor memory/cognitive disorders without dementia (deterioration
      without dementia, DWD), 111 patients with Alzheimer-type dementia (ATD).
      Statistical description. Multivariate linear regression. Crossed validation.
      Internal consistency and test-retest (n = 48). The mean scores (SD) obtained were
      as follows. CONTROLS: ADAS-Cog = 8.0 (3.4), ADAS-Noncog = 2.9 (2.9), ADAS-Tot =
      10.9 (4.6). DWD: ADAS-Cog = 11.37 (5.1), ADAS-Noncog = 4.9 (4.3), ADAS-Tot = 16.2
      (7.0). ATD: ADAS-Cog = 31.8 (5.1), ADAS-Noncog = 10.3 (4.3), ADAS-Tot = 42.2
      (20.7). Multiple regression analysis revealed that educational level and age were
      significantly associated with the ADAS-Cog score. The internal consistency of the
      ADAS-Cog was 0.963. The test-retest procedure yielded linear correlation,
      coefficients of 0.93 for the ADAS-Cog, 0.86 for the ADAS-Noncog and 0.95 for the
      ADAS-Tot. Age and educational level/schooling are associated to the earned on the
      ADAS-Cog instrument. The present Spanish version of the ADAS has high internal
      consistency and reproducibility. The instruments can be use for assessment in
      Spanish populations.

PMID- 9147455
TI  - [Cerebrovascular stroke, the cause of the death of the caliph al-Hakam II].
AB  - al-Hakam II was the ninth sovereign in the Hispano-Omeyan dynasty and the second
      caliph of Spain under the Moors. In the night of the 1st of October 976 he died
      as the result of a disease that had afflicted him for two years old.
      Cerebrovascular stroke first manifested as hemiplegia. The disease that afflicted
      the caliph was called al-'illat alfalichiya, or alfeliche in Castilian Spanish,
      which means the disease of hemiplegia. The caliph was 61 years old and led a
      sedentary life and was therefore predisposed to suffer ischemic cerebrovascular
      events. Climate may have played a role in triggering the stroke. Several authors
      have found that the incidences of ischemic infarcts and intracranial hemorrhages
      increase during the winter months and on cold days, particularly in patients
      under 65. The chronicler of the al-Razi period tells us that heavy snow fell in
      and around Cordoba in 974 and that the following months saw rain and strong
      winds. We can deduce that caliph al-Hakam II died of a cerebrovascular event and
      that, based on the few data available, it is likely that the infarction was
      ischemic and of atherothrombotic origin. Caliph al-Hakam II moved his household
      from Madinat al-Zahra' to Alcazar de Cordoba as a result of the "recommendation
      of his doctors because the cold of the Sierra stirred up his humors". This
      interpretation is correct according to Arab medicine, which is following the line
      of the ancient Greeks regarding natural faculties, the elements and their
      corresponding humors.

PMID- 9147456
TI  - [Postgraduate education of neurologists].

PMID- 9147457
TI  - [Shot wounds to the cerebral cortex].

PMID- 9147458
TI  - [Detection of cerebral microemboli by transcranial Doppler imaging (DTC)].

PMID- 9147459
TI  - [Reversible cortical blindness associated with bilateral occipital lesions caused
      by cyclosporin A: report of two cases].
AB  - We report two cases of encephalopathy with cortical blindness associated with
      reversible bioccipital lesions in transplanted patients (of the kidney and bone
      marrow) who were being treated with cyclosporin A. We briefly discuss the
      pathogenesis of symptoms and review the literature.

PMID- 9147460
TI  - [Bilateral asymmetric degeneration of the striatum as a cause of senile
      hemiballism].
AB  - We report the case of an 82-years old woman with sporadic acute hemiballism
      associated with bilateral striatal degeneration of non vascular origin which was
      most severe in the side contralateral to the hemiballism. The patient's
      neuropathological lesions resembled those of patients with senile chorea.
      Although hemiballism has never been described as an isolated manifestation of
      primary degeneration of the striatum, it may so occur in elderly patients with
      hemiballism.

PMID- 9147461
TI  - [Relations among multiple sclerosis, Hodgkin's disease and idiopathic
      thrombocytopenic purpura. Letter].

PMID- 9147462
TI  - Extracorporeal membrane oxygenation, a favourable outcome?

PMID- 9147463
TI  - [The years are passing].

PMID- 9147464
TI  - [The effectiveness of the trigonoplasty in the treatment of the primary
      vesicoureteral reflux].
AB  - Trigonoplasty is a minor surgical procedure to treat vesicoureteral reflux that
      preserves the integrity of the vesicoureteral junction. This technique was
      introduced in 1984 by Gil Vernet. Between 1989 and 1995 we performed
      trigonoplasty in 20 children from 6 to 15 years old with primary vesicoureteral
      reflux. In our study 15 patients had bilateral vesicoureteral reflux and five
      were unilateral, they had 35 refluxing units. Gil Vernet's trigonoplasty was
      performed after a five year observational treatment and it was always indicated
      in children with special wide trigone (1 grade I, 14 grade II, 17 grade III and 3
      grade IV). Surgery was successful in 94% of the patients controlled one year
      after. Unilateral reflux recurrence in two patients. We consider that
      trigonoplasty is a good procedure with indication in patients with vesicoureteral
      reflux with wide trigone. The procedure shorten the postoperative hospital stay
      and offers a similar percentage of good results as other techniques.

PMID- 9147465
TI  - [Pancreatic pseudocyst. Review of 22 cases].
AB  - The management of 22 children with pseudocyst of the pancreas presenting over a
      15-year period at three pediatric Hospitals is reviewed. The mean age of patients
      was 7 years being more common in boys (17:5). Ninety one per cent were due to
      trauma, while in 9% the cause was unknown. Vomiting (81.8%), abdominal pain
      (77.2%), a mass (72.7%), fever (31.8%) and anorexia (31.8%) were the most
      frequent findings. The diagnosis was confirmed by finding hyperamylasemia
      (elevated in 72.7% of cases), by barium meal and ultrasound. Operative treatment
      included external drainage in 4 children, cystgastrostomy in 9, cystjejunostomy
      in 6, and excision in 1. One patient was successfully managed nonoperatively and
      another had spontaneous gastric drainage. There were no deaths or significative
      complications in this series.

PMID- 9147466
TI  - [The treatment of the primary intrarenal reflux. Is the surgery always
      necessary?].
AB  - THE AIMS OF THIS STUDY was to evaluate the relationship between intrarenal reflux
      (I.R.R.) and reflux nephropathy (R.N.) in order to know the results of surgical
      and non surgical treatment. Fifty one children with 64 kidneys with primary
      I.R.R. were studied. 53% of them were less than one year of age. Initial
      examination were: urography, ultrasounds, cystography and DMSA scan; the follow
      up was done with ultrasounds, DMSA scan and cystography. When no R.N. was
      present, grade of reflux was < IV, and age < 12 years, a non surgical treatment
      was indicated. RESULTS: During first examination R.N. was demonstrated in 47% of
      kidneys; the main difference was the grade of reflux: 16/44 II-III (36%) and
      14/20 IV-V (70%). Surgical treatment was performed in 42 (82%) children and non
      surgical in 9 (18%). Reflux stopped in 98% and 100%, respectively. Only one
      child, without R.N., developed a new renal scar, and a previous R.N. progressed
      in two. I.R.R. can be treated successfully without surgery in selected cases.

PMID- 9147467
TI  - [Clinical and anatomopathological study of the contralateral tests in the
      unilateral cryptorchidism].
AB  - We have operated on 2204 cryptorchid testis between 1972 and 1995. We took
      pathological specimens, not only in the undescended testis but also in the
      normally descended contralateral testis in 122 children. Clinical, surgical and
      anatomopathological records were reviewed. Moreover, we have studied the
      spermiograms in 10 young men. We found the Tubular Fertility Index (TFI) was
      abnormal in 37% of the contralateral testis. In 5 cases we didn't find germinal
      line. The Tubular Diameter was abnormal in 6.5% of the contralateral testicles
      only. When we compared the anatomopathological records in the contralateral
      testis depending on the surgical age and the surgical location of the undescended
      testis, we didn't find significant differences. When we studied the spermiograms
      in the 10 young men we obtained some cases where the TFI and the spermiogram were
      discordant. In conclusion, more than 1/3 of the children with unilateral
      undescended testis have an abnormal TFI in both testis. Moreover, neither the
      surgical age nor surgical location of the undescended testis have an influence on
      the contralateral TFI. Finally, according to the spermiogram results we should
      question TFI as a fertility index.

PMID- 9147468
TI  - [The treatment of the tracheobronchomalacia in pediatric age].
AB  - OBJECTIVE: Aortopexy is the more extended treatment for severe tracheomalacia,
      when it fails, reintervention and other procedures are necessary. We present our
      experience in the treatment of this pathology. MATERIAL AND METHODS:
      Tracheomalacia, bronchomalacia and tracheobroncomalacia cases during a twelve
      year period (1983-1995) were reviewed (type, age, symptoms, surgical procedures
      and results were collected). RESULTS: Nineteen patients (9 males, 10 females)
      presented tracheobronchomalacia in our Hospital. Diagnosis was made by
      bronchoscopy in all of them: nine cases of tracheomalacia, five bronchomalacias
      and five suprastomal malacias were found. Mean diagnosis age was twenty four
      months (newborn-twelve years). Ten patients were managed nonoperatively, five
      with anterior cricoideal suspension and two cases were treated by aortopexy; one
      of them, after 2 months of respiratory stridor and recurrent respiratory arrest,
      needed an endoscopically placed intraluminal expandable Palmaz Prothesis. This
      prothesis was removed two years later. In this moment, the patient is doing well
      without stridor or respiratory symptoms.

PMID- 9147469
TI  - [The treatment of the tracheobronchial stenosis by extracorporeal circulation].
AB  - Six children with tracheobronchial stenosis secondary to cardiovascular ring were
      operated with extracorporeal surgery. Three of them with pulmonary sling had a
      tracheobroncoplasty with costal cartilage, one with xiphoides appendix and
      another with pericardio. One girl 2 years old was operated resecting three
      tracheal rings and anastomosis end to end. The child that was operated with
      pericardio died with infection and sepsis three months after the operation. The
      other five are well five, four and two years after plasty.

PMID- 9147470
TI  - [Experimental free muscle transplantation. Is autologous graft on the distal
      esophagus viable?].
AB  - Experimental free muscle transplantation has resulted in some successful clinical
      applications. AIM: The possibility that this type of transplantation could act as
      a sphincteric mechanism motivated us to start by assessing the viability of
      autologous skeletal grafts on the distal esophagus of laboratory animals.
      MATERIAL AND METHODS: Twenty transplants of previously denervated free plantaris
      muscle grafted on the distal esophagus of Sprague-Dawley rats were evaluated at
      the 1st, 2nd, 4th, 8th and 16th posttransplant week. Histological and
      histochemical studies were performed to evaluate general features of the grafts
      and the muscle fibers condition. RESULTS: One and two weeks after transplant the
      grafts show large areas of necrosis with inflammatory infiltrate. Between the 2nd
      and the 4th week, as revascularization and motor endplates become significant,
      the areas of necrosis begin to regress and they almost disappear by the 8th week.
      Since the 4th week after transplant, regenerated muscle fibers demonstrate
      morphological and biochemical features similar to normal. CONCLUSIONS:
      Experimental free plantaris muscle transplantation on the distal esophagus is
      viable and shows revascularized and reinnervated muscle fibers from the 8th week
      after transplant on, and at least until the 16th. These fibers have the
      structural and metabolic properties enabling contractile function. This original
      model may allow further investigation of some features related to pathophysiology
      and therapy of gastroesophageal reflux.

PMID- 9147471
TI  - [Wandering spleen syndrome in childhood].
AB  - Wandering spleen is a clinical condition in which an absence of ligaments and a
      long vascular pedicle allows the spleen to move freely in the abdomen. It is a
      rare entity in children but the exactly incidence is unknown because most of them
      are asymptomatic. The most common form of presentation is acute, chronic or
      intermittent abdominal pain caused by spleen torsion. Ultrasonography is the
      elective diagnostic method, but frequently diagnosis is made after surgery. We
      report two cases with acute splenic torsion in children and we discuss the
      clinical presentation, etiology, diagnostic procedures and management. We
      conclude that splenopexy--if possible--is the treatment of choice in children.

PMID- 9147472
TI  - [Hepatoporto-appendicostomy. Our experience in 3 cases of biliary cystic
      disease].
AB  - This report details our preliminary experience with hepaticoporto-appendicostomy
      in three patients with biliary cystic disease. The surgical procedure was total
      resection of choledochal cyst and vascularized appendix interposition between
      biliary tree and duodenum. The children have been followed by clinical,
      ultrasonography and endoscopic (ECPR) during a period between 1-4 years. There
      was no episodes of ascending colangitis. All the patients remain free of jaundice
      and the biochemical abnormalities have become normal three months after
      interposition. Our results suggest that this procedure is more physiologic than
      the standard bilioenteric derivation Roux-in-Y, because allow bile to enter
      freely to duodenum and prevent reflux, stasis and ascending cholangitis. This
      procedure allows postoperative endoscopic valoration, not possible in another
      kind of bilioenteric derivations.

PMID- 9147473
TI  - 3H-adenosine uptake selectively labels rod horizontal cells in goldfish retina.
AB  - There are four types of horizontal cell in the goldfish retina, three cone- and
      one rod-type. The neurotransmitter of only one type, the H1 (cone) horizontal
      cell, has been identified as GABA. 3H-adenosine uptake was examined as a possible
      marker for the other classes of horizontal cell. Isolated goldfish retinae were
      incubated in 3H-adenosine (10-40 microCi) in HEPES-buffered saline for 30 min,
      then fixed, embedded in plastic, and processed for light-microscopic
      autoradiography (ARG). For double-label immuno/ARG studies, 1-micron-thick
      sections were processed for GABA postembed immunocytochemistry, then for ARG. 3H
      adenosine uptake was localized to cone photoreceptors, presumed precursor cells
      in the proximal outer nuclear layer, and to a single, continuous row of
      horizontal cell bodies in the inner nuclear layer. No uptake was localized to the
      region of horizontal cell axon terminals. 3H-adenosine uptake did not colocalize
      with GABA-IR in H1 horizontal cells, but it did colocalize with adenosine
      deaminase immunoreactivity. It is concluded that 3H-adenosine uptake selectively
      labels rod horizontal cells in the goldfish retina based on position and staining
      pattern, which are similar to rod horizontal cells stained by Golgi or HRP
      injection methods. The use of 3H-adenosine uptake may provide a useful tool to
      study other properties of rod horizontal cells (i.e. development) as well as
      provide clues as to the transmitter used by these interneurons.

PMID- 9147474
TI  - Brain-stem afferents upon retinal projecting isthmo-optic and ectopic neurons of
      the pigeon centrifugal visual system demonstrated by retrograde transneuronal
      transport of rhodamine beta-isothiocyanate.
AB  - Brain-stem afferents to the n. isthmo-opticus (NIO) and ectopic neurons (EN) of
      the centrifugal visual system (CVS) were determined in the pigeon using the
      retrograde transneuronal transport of the fluorescent dye Rhodamine beta
      isothiocyanate (RITC) after its intraocular injection. In other experiments,
      either RITC was injected into various periocular tissues (controls) or the
      retrograde tracer Fluoro-gold (FG) was injected stereotaxically in the NIO.
      Following intraocular injections, the RITC retrograde labeling of cell bodies was
      observed contralaterally in the NIO and EN and transneuronally in layers 9/10 of
      the optic tectum, area ventralis-Tsai, zona peri-NIII, mesencephalic and pontine
      reticular formation (PRF), n. linearis caudalis-raphe, and bilaterally within a
      region referred to as zona peri-n.NVI (Zp-n.NVI) immediately underlying the
      abducens nerve nucleus. None of the above structures were labeled after RITC
      periocular injections. The FG labeling revealed that the tectal efferent neurons
      were mainly medium-sized, multipolar cells whose dendrites extended superficially
      to retino-recipient tectal layers 6 and 5. Quantitative measurements of the
      distribution of layers 9/10 RITC-labeled neurons indicated the highest densities
      to be localized within the ventral tectum corresponding to the representation of
      the dorsal retina and inferior visual field. We suggest that visual and nonvisual
      brain-stem afferents upon NIO and EN may play a role in the proposed mechanism of
      the avian CVS in attention, ground-feeding behavior, and modulation of retinal
      sensitivity.

PMID- 9147475
TI  - Molecular cloning and localization of rhodopsin kinase in the mammalian pineal.
AB  - Several retinal photoreceptor proteins involved in phototransduction have also
      been found in the mammalian pineal. This study demonstrates that rat and human
      pineals express protein kinases that are identical to the corresponding rod
      photoreceptor rhodopsin kinases. The deduced amino acid sequence of rat and human
      rhodopsin kinases have 84% sequence similarity to the earlier reported sequence
      of the bovine retinal enzyme, with complete conservation of the topological
      regions containing the position of the catalytic domain and sites of
      posttranslational modifications. Rat pineal also expresses rod opsin and putative
      blue cone opsin. Using immunocytochemistry, rod opsin and rhodopsin kinase were
      found to be co-localized in pinealocytes in the human tissue. These data
      demonstrate that the mammalian pineal contains light-sensitive opsins and a
      kinase involved in their inactivation. These findings correlate with an earlier
      report that neonatal rats show extraretinal light sensitivity, and suggest that a
      functional photoreceptive system may be present in the adult mammalian pineal.

PMID- 9147476
TI  - Modulation of rod, but not cone, cGMP-gated photoreceptor channels by calcium
      calmodulin.
AB  - Inside-out patches containing cGMP-gated channels were excised from catfish rod
      or cone outer segments and held under voltage clamp. The net cGMP-dependent
      currents elicited by saturating and subsaturating concentrations of cGMP at +/-30
      mV were measured and the dependence of current upon cGMP concentration was
      determined. The apparent affinity of the channel for its ligand was estimated by
      fitting these data with the Hill equation. The concentration of cGMP required to
      give half the maximum current (K1/2) in rod and cone channels at +30 mV was
      approximately 28 microM and approximately 37 microM, respectively, and was weakly
      voltage dependent. Thus, cone channels have an intrinsically higher K1/2 than rod
      channels. For both types of channel, the Hill coefficient was approximately 2.3.
      In the presence of calcium-calmodulin, the apparent affinity of the rod channel
      for cGMP decreased by about twofold, but the apparent affinity of the cone
      channels was unaffected. These results indicate that the open probability of the
      cone channel for its ligand cannot be modulated by calmodulin. This represents
      the first significant departure between rod and cone photoreceptors in mechanisms
      used by phototransduction and suggests that the beta subunit of the cone channel
      must be different from that of the rod channel.

PMID- 9147477
TI  - Ocular dominance columns and local projections of layer 6 pyramidal neurons in
      macaque primary visual cortex.
AB  - To study the relationship between ocular dominance columns (ODCs) and axonal
      projections of individual layer 6 pyramidal neurons in the primary visual cortex,
      neurons were intracellularly labeled with biocytin in live slices prepared from
      macaque monkeys that had received an intravitreal injection of tetrodotoxin
      (TTX). The TTX injection indirectly causes a decrease in cytochrome oxidase (CO)
      expression in the cortical ODCs corresponding to the treated eye (Wong-Riley &
      Carroll, 1984). Sections from slices with labeled layer 6 neurons were double
      stained for biocytin and CO, to allow visualization of neuronal processes as well
      as ODCs. Twenty-seven layer 6 pyramidal neurons in ODC-labeled slices were
      analyzed. These neurons were classified according to the criteria of Wiser and
      Callaway (1996). Eight of these are class I neurons, which have dense axonal
      projections to the monocular layer 4C. The remaining 19 are class II neurons
      which project primarily to the binocular layers outside 4C. Among class I
      neurons, two have dense axonal arbors in layer 4C alpha (type I alpha), one in
      layer 4C beta (type I beta), and two throughout the depth of layer 4C (type IC).
      None of these neurons have ODC-specific axonal arbors. The remaining three class
      I neurons have focused axonal projections in layers 4C beta and 4A (type I beta
      A). All three appear to have axonal arbors predominantly within their home ODC in
      layer 4C. The axonal arbors of class II neurons do not appear to relate to ODCs
      in any specific fashion.

PMID- 9147478
TI  - Localization of the CD15 carbohydrate epitope in the vertebrate retina.
AB  - The distribution of the carbohydrate epitope CD15, a putative cell adhesion
      molecule, was studied in adult vertebrate retinas by light-microscopic
      immunohistochemistry. Except for Old World primates, in which no immunoreactivity
      was detectable, all other species expressed the epitope on retinal interneurones.
      Subpopulations of stratified amacrine cells were found in all species with the
      exception of bats and marmoset monkeys, and bipolar cells were immunoreactive in
      frogs and all amniotic animals. Ganglion cells were labelled in urodelian, in all
      sauromorphian, as well as in some mammalian species. In some species, the
      distribution of immunoreactive neurones was correlated to areas of retinal
      specialization such as the visual streak in frogs and the dorsotemporal field in
      birds. In these parts of the retina with enhanced visual acuity, more CD15
      glycosylated bipolar cells were found than in other parts. Among mammals,
      labelled bipolar cells were found exclusively in species with cone-dominated
      retinas. This comparative study shows that CD15 expression is consistently
      membrane associated in morphologically defined subsets of amacrine, bipolar, and
      ganglion cells throughout the vertebrate phylum. Its distribution pattern was
      found to depend more on the visual behavior of a given species (cone-dominated or
      rod-dominated retina) than on phylogenetic proximity between species.

PMID- 9147479
TI  - Principal neuronal organization in the frog optic tectum revealed by a current
      source density analysis.
AB  - In the frog optic tectum, the spatiotemporal pattern of neuronal activity evoked
      by electrical stimulation of the optic tract was examined by means of a current
      source density (CSD) analysis. The CSD depth profile was highly reproducible in
      different experiments. In all seven CSD profiles, three current sinks A, B, and D
      were observed in the retinorecipient layers. Four out of the seven profiles show
      additional two sinks C and E below the retinorecipient layers. Very small and
      short lasting sinks related to afferent fiber activities precede sinks A and B by
      about 1 ms, which could be accounted for by monosynaptic delay, in the
      corresponding depth region. The earliest prominent sink A at the bottom of the
      retinorecipient layers reflects only excitatory monosynaptic activities derived
      from R3 and/or R4 retinal ganglion cells. The second prominent sink B in the
      superficial retinorecipient layer is composed partly of excitatory monosynaptic
      activity from medium-sized myelinated optic fibers. It may involve excitatory
      monosynaptic activity from unmyelinated optic fibers and further polysynaptic
      activity. The fourth prominent sink D in the intermediate retinorecipient layer
      partially reflects excitatory monosynaptic activity derived from unmyelinated
      optic fibers. It may also involve further polysynaptic activity. In contrast with
      these three sinks, the third prominent sink C and fifth sink E exclusively
      reflect intratectal polysynaptic activity that has not been reported in any
      previous CSD studies in the frog optic tectum. These sinks almost overlap
      spatially in the tectal layer. We also measured the intratectal resistance
      changes and computed inhomogeneous CSD depth profiles to show that the results
      from homogeneous CSD computation assuming constant conductivity are valid for our
      present study. Finally, we compared the present results with previously reported
      CSD studies on the frog optic tectum and discuss consistencies and discrepancies
      among these experiments.

PMID- 9147480
TI  - Projection status of calbindin- and parvalbumin-immunoreactive neurons in the
      superficial layers of the rat's superior colliculus.
AB  - Immunocytochemistry and retrograde labeling were used to define the thalamic
      projections of calbindin- and parvalbumin-containing cells in superficial layers
      of the rat's superior colliculus (SC). Quantitative analysis revealed that 90.8
      +/- 2.2% (mean +/- standard deviation) of the calbindin-immunoreactive neurons in
      the stratum griseum superficiale (SGS) projected to the dorsal lateral geniculate
      nucleus (LGNd) and that 91.3 +/- 4.3% of calbindin-immunoreactive neurons in the
      stratum opticum (SO) projected to the lateral posterior nucleus (LP). In
      contrast, only 17.3 +/- 2.5% of parvalbumin-immunoreactive neurons in the SGS
      were found to project to the LGNd and 16.5 +/- 3.1% of the parvalbumin
      immunoreactive SO cells were retrogradely labeled after LP injections. Few of the
      parvalbumin-immunoreactive neurons in either the SGS (7.2 +/- 2.5%) or the SO
      (9.2 +/- 2.5%) were GABA positive. The retrograde-labeling results suggest that
      parvalbumin-immunoreactive neurons in the rat's SO and SGS may either be
      primarily interneurons or have descending projections, while calbindin-containing
      cells are primarily thalamic projection neurons. These results are consistent
      with data from other rodents, but almost exactly the opposite of data that have
      been reported for the cat for these same populations of SC projection neurons.
      Such interspecies differences raise questions regarding the functional importance
      of expressing one calcium-binding protein versus another in a specific neuronal
      population.

PMID- 9147481
TI  - Immunological demonstration of Gq-protein in Limulus photoreceptors.
AB  - The phototransduction cascade in invertebrates involves the coupling of rhodopsin
      activation to the action of the enzyme phospholipase C. This step is performed by
      G-proteins. An antibody against the alpha-subunit of a mouse Gq type G-protein
      recognized protein bands in Western blots of lateral eye and ventral nerve
      photoreceptors of Limulus. The protein bands had an apparent molecular mass of
      about 42 kDa. The antibody also recognized protein bands of a similar molecular
      mass in immunoblots of brain and intestine tissue. Immunoreactivity was found in
      lateral eye frozen sections where it was confined to the rhabdom region. When the
      antibody was applied to ultrathin sections of ventral nerve photoreceptors, the
      highest density of labeling was found on the rhabdomeral microvilli, but gold
      particles were also scattered in the cytoplasm. We conclude that a G-protein of
      the type Gq participates in the phototransduction of Limulus.

PMID- 9147482
TI  - Comparison of contrast-normalization and threshold models of the responses of
      simple cells in cat striate cortex.
AB  - In almost every study of the linearity of spatiotemporal summation in simple
      cells of the cat's visual cortex, there have been systematic mismatches between
      the experimental observations and the predictions of the linear theory. These
      mismatches have generally been explained by supposing that the initial
      spatiotemporal summation stage is strictly linear, but that the following output
      stage of the simple cell is subject to some contrast-dependent nonlinearity. Two
      main models of the output nonlinearity have been proposed: the threshold model
      (e.g. Tolhurst & Dean, 1987) and the contrast-normalization model (e.g. Heeger,
      1992a,b). In this paper, the two models are fitted rigorously to a variety of
      previously published neurophysiological data, in order to determine whether one
      model is a better explanation of the data. We reexamine data on the interaction
      between two bar stimuli presented in different parts of the receptive field; on
      the relationship between the receptive-field map and the inverse Fourier
      transform of the spatial-frequency tuning curve; on the dependence of response
      amplitude and phase on the spatial phase of stationary gratings; on the
      relationships between the responses to moving and modulated gratings; and on the
      suppressive action of gratings moving in a neuron's nonpreferred direction. In
      many situations, the predictions of the two models are similar, but the contrast
      normalization model usually fits the data slightly better than the threshold
      model, and it is easier to apply the equations of the normalization model. More
      importantly, the normalization model is naturally able to account very well for
      the details and subtlety of the results in experiments where the total contrast
      energy of the stimuli changes; some of these phenomena are completely beyond the
      scope of the threshold model. Rigorous application of the models' equations has
      revealed some situations where neither model fits quite well enough, and we must
      suppose, therefore, that there are some subtle nonlinearities still to be
      characterized.

PMID- 9147483
TI  - Calretinin in the cat retina: colocalizations with other calcium-binding
      proteins, GABA and glycine.
AB  - Immunocytochemical techniques were used to determine the distribution of the
      calcium-binding protein calretinin in the cat retina. Comparisons were made with
      parvalbumin and calbindin as well as with the inhibitory neurotransmitters GABA
      and glycine. Calretinin immunoreactivity was seen in horizontal cells and
      multiple subpopulations of amacrine and ganglion cells. Cone outer segments were
      also stained. Calbindin immunoreactivity was present in cone photoreceptors,
      horizontal cells, at least two subtypes of cone bipolar cell, numerous amacrine
      cells, and cells residing in the ganglion cell layer. Heavy staining for
      parvalbumin was found in both A- and B-type horizontal cells, distinct
      subpopulations of amacrine and ganglion cells, and a small population of cone
      photoreceptor cells. To confirm the identity of cone photoreceptors, comparisons
      were made with retinas stained for opsins specific for red/green or blue cones
      (Szel et al., 1986). The localization of parvalbumin corresponded with that of
      blue-type cones only whereas calretinin and calbindin staining showed the same
      distribution as both red/green and blue cones. Double-label immunofluorescence
      studies revealed colocalization of all three of the calcium-binding proteins in a
      number of neurons including horizontal cells and AII amacrine cells. To assess a
      possible transmitter-specific relationship for calretinin, double-label studies
      were carried out with GABA and glycine. However, the staining patterns for each
      of these inhibitory amino acids differed substantially from that of calretinin.
      The possibility remains that calretinin and other calcium-binding proteins may
      play a role in neurotransmission through interactions with receptors or second
      messenger agents.

PMID- 9147484
TI  - The effect of a moving distractor on the initiation of smooth-pursuit eye
      movements.
AB  - As a step toward understanding the mechanism by which targets are selected for
      smooth-pursuit eye movements, we examined the behavior of the pursuit system when
      monkeys were presented with two discrete moving visual targets. Two rhesus
      monkeys were trained to select a small moving target identified by its color in
      the presence of a moving distractor of another color. Smooth-pursuit eye
      movements were quantified in terms of the latency of the eye movement and the
      initial eye acceleration profile. We have previously shown that the latency of
      smooth pursuit, which is normally around 100 ms, can be extended to 150 ms or
      shortened to 85 ms depending on whether there is a distractor moving in the
      opposite or same direction, respectively, relative to the direction of the
      target. We have now measured this effect for a 360 deg range of distractor
      directions, and distractor speeds of 5-45 deg/s. We have also examined the effect
      of varying the spatial separation and temporal asynchrony between target and
      distractor. The results indicate that the effect of the distractor on the latency
      of pursuit depends on its direction of motion, and its spatial and temporal
      proximity to the target, but depends very little on the speed of the distractor.
      Furthermore, under the conditions of these experiments, the direction of the eye
      movement that is emitted in response to two competing moving stimuli is not a
      vectorial combination of the stimulus motions, but is solely determined by the
      direction of the target. The results are consistent with a competitive model for
      smooth-pursuit target selection and suggest that the competition takes place at a
      stage of the pursuit pathway that is between visual-motion processing and motor
      response preparation.

PMID- 9147485
TI  - Effects of adaptation level and hypoglycemia on function of the cat retina during
      hypoxemia.
AB  - Acute hypoxemia (low PaO2) leads to changes in oxygen consumption and electrical
      responses of the outer retina of cats, but inner retinal ERG components and
      ganglion cell responses have been shown to be quite resistant to hypoxemia. The
      purpose of this study was to determine whether the resistance of the inner retina
      depends on (1) the stimulus conditions, specifically the degree of light
      adaptation; and (2) the ability of the photoreceptors to increase glycolysis
      during hypoxemia. To address these issues, recordings of single ganglion cell
      action potentials and of the b-wave and scotopic threshold response (STR) of the
      electroretinogram (ERG) were made from the eyes of anesthetized cats during
      hypoxemia alone and hypoxemia plus hypoglycemia. Ganglion cells appeared to be
      equally resistant to hypoxemia at high and low backgrounds (3.3 to 9.7 log
      equivalent quanta(555 nm)-deg-2(-s)-1), and the STR, recorded with dim stimuli
      during dark adaptation, when photoreceptor oxygen consumption is most susceptible
      to hypoxemia, was unchanged until PaO2 was below 30 mm Hg. The amplitude of the b
      wave was similarly resistant to hypoxemia when the animal was normoglycemic.
      During hypoglycemia, however, both the b-wave and the STR became more sensitive
      to hypoxemia, beginning to change at PaO2s as high as 50 mm Hg when blood glucose
      was 40-50 mg/dl. It is argued that hypoglycemia limits or prevents the increased
      glycolytic ATP production that would ordinarily occur when the photoreceptor
      oxygen supply decreases, and that increased photoreceptor glycolysis is essential
      in the protection of the retina against mild hypoxemia.

PMID- 9147486
TI  - Modulation of endogenous dopamine release in the fish retina by light and
      prolonged darkness.
AB  - The effect of light stimuli and prolonged darkness on the release of endogenous
      dopamine was measured in the white perch and hybrid bass retinas. Isolated
      retinas were superfused and released dopamine was measured using extraction and
      high-pressure liquid chromatography separation techniques. Potassium-induced
      release did not depend on the background illumination nor on the period of
      previous darkness. Steady white light did not affect release, but flickering
      light of 2 Hz increased release about two-fold. During prolonged darkness, the
      release of dopamine increased steadily over the test period of 2 h, but only if
      the experiments were performed at night. During the day such an increase was not
      observed. The increased release during prolonged darkness at night was turned off
      by a short period of steady white light. The release patterns obtained from the
      white perch and the hybrid bass were similar. However, the hybrid bass retina
      showed much lower levels of dopamine than did the white perch retina.

PMID- 9147487
TI  - Quadrature subunits in directionally selective simple cells: spatiotemporal
      interactions.
AB  - I explore here whether linear mechanisms can explain directional selectivity (DS)
      in simple cells of the cat's striate cortex, a question suggested by a recent
      upswing in popularity of linear DS models. I chose a simple cell with a space
      time inseparable receptive field (RF), i.e. one that shows gradually shifting
      latency across space, as the RF type most likely to depend on linear mechanisms
      of DS. However, measured responses of the cell to a moving bar were less
      modulated, and extended over a larger spatial region than predicted by two
      different popular "linear" models. They also were more DS in exhibiting a higher
      ratio of total spikes for the preferred direction. Each of the two models used
      for comparison has a single "branch" with a single spatiotemporally inseparable
      linear filter followed by a threshold, hence, a- "1-branch" model. Nonlinear
      interactions between pairs of bars in a 2-bar linear superposition test of the
      cell also disagreed in time-course with those of the 1-branch models. The only
      model whose 1-bar and 2-bar predictions matched the measured cell (including a
      complete "4-branch" motion energy model that matches complex cells) has two
      branches that differ in phase by about 90 deg, i.e. in quadrature. Each branch
      has its own threshold that helps define the preceding spatiotemporal unit as a
      subunit even after the outputs of the two branches are summed. As subunit phases
      differ by only 90 deg, flashing bar responses of the 2-subunit model are similar
      to those of the 1-subunit model. Therefore, the number of subunits is hidden from
      view when testing with a conventional stationary bar. In summary, movement
      responses and nonlinear interactions between pairs of bars in the measured cell
      matched those of the 2-subunit model, while they disagreed with the popular 1
      subunit model. Thus, multiple nonlinear subunits appear to be necessary for DS,
      even in simple cortical cells.

PMID- 9147488
TI  - Quadrature subunits in directionally selective simple cells: counterphase and
      drifting grating responses.
AB  - Here we examine further the basis for directional selectivity (DS) in simple
      cells of the cat's striate cortex. We use a distinctly different input stimulus
      and different analysis of the output signal for the same type of space-time
      inseparable receptive field (RF) that was measured with flashing bars in the
      companion paper (Emerson, 1997). As in the companion paper, we have mimicked a
      popular "linear" model with a single "branch" that consists of a linear
      spatiotemporal filter followed by a soft threshold, which should mimic any simple
      cells that have a single subunit. Counterphase sinusoidal measurements of such a
      configuration always generate elliptically shaped polar plots of amplitude versus
      temporal phase, often pinched along the minor axis because of a high threshold.
      However, for many spatiotemporal frequencies, such polar phase plots, as measured
      in simple cells by others, show a consistent rotational phase skew. Here we apply
      counterphase analysis to the same 2-branch model as developed in the companion
      paper. We show that the model accounts for the skew as the summation of signals
      from linear filters separated spatially and temporally by approximately 90 deg
      (i.e. in spatiotemporal phase quadrature), each separated from the output stage
      by a soft-threshold nonlinearity. We also prove conclusively that such skew
      cannot be generated by a single-subunit configuration. This demonstration
      supports the proposed two-subunit structure for DS simple cells, such as in the
      example from the companion paper, which has strong linear contributions from its
      inseparable RF. The presence of at least two nonlinear subunits appears to be an
      obligatory concomitant of DS in all visual cortical cells. The primary function
      of these subunits may be to enhance the strength of responses to images moving in
      the preferred direction, as in complex cells. However, subunits may also aid in
      identifying the moving object through overcoming, at least partially, the phase
      concealing properties of the neuron's threshold by generating a steady signal
      that effectively decreases the threshold for the preferred direction.

PMID- 9147489
TI  - Glutamate containing neurons in the cat superior colliculus revealed by
      immunocytochemistry.
AB  - Glutamate is the probable neurotransmitter of both retinal and cortical afferents
      to the cat superior colliculus (SC). The present study shows that glutamate is
      also contained in many postsynaptic neurons in SC. The distribution, morphology,
      and ultrastructure of neurons in SC were examined using glutamate antibody
      immunocytochemistry. Labeled cells were widely distributed throughout, but a
      specific laminar pattern was evident. Relatively few cells were found in the
      zonal and upper superficial gray layers (SGL). A dense band of intensely labeled
      neurons was found within the deep superficial gray and upper optic layers. Many
      cells were also labeled in the deeper layers. Labeled cells had varied sizes and
      morphologies. Soma diameters ranged from 9-67 microns, with a mean of 22 microns.
      Cells with stellate, vertical fusiform, and multipolar morphologies were labeled.
      Cells in the deep subdivision all had morphologies and sizes typical of
      projection neurons. To determine if labeled cells in the dense band were also
      projection neurons, WGA-HRP was injected into the lateral posterior nucleus and
      these sections were double-labeled with the glutamate antibody. Over one-half of
      cells in the dense band that were labeled by HRP were also obviously labeled by
      antibody. At the electron-microscope level, both medium- and large-sized neurons
      were also labeled by glutamate antibodies. These cells had different but
      characteristic morphologies.

PMID- 9147491
TI  - Free radical pathology and antioxidant defense in schizophrenia: a review.
AB  - There is increasing evidence that free radical-mediated CNS neuronal dysfunction
      is involved in the pathophysiology of schizophrenia. Free radicals (oxyradicals,
      such as superoxide, hydroxyl ions, and nitric oxide) cause cell injury when they
      are generated in excess or the antioxidant defense is impaired. Both of these
      processes seem to be affected in schizophrenia. Evidence of excessive oxyradical
      generation is premised on the assumption that there is increased catecholamine
      turnover, though there is little direct evidence to support such a view, which is
      further accentuated by neuroleptic treatment. However, antioxidant enzymes
      (superoxide dismutase, SOD; glutathione peroxidase, GSHPx; and catalase, CAT)
      which are constitutively expressed in all tissues, are found to be altered in
      erythrocytes of schizophrenic patients. Also, possible oxyradical-mediated injury
      to CNS is suggested by increased lipid peroxidation products in cerebrospinal
      fluid and plasma, and reduced membrane polyunsaturated fatty acids (PUFAs) in the
      brain and RBC plasma membranes. The brain is more vulnerable to oxyradical
      mediated injury,because its membranes are preferentially enriched in oxyradical
      sensitive PUFAs, and damaged adult neurons cannot be replaced. In addition to
      their pathological role, oxyradicals have critical physiological functions in
      neuronal development, differentiation, and signal transduction, all of which may
      be altered in some cases of schizophrenia. It may be possible to define cellular
      injury processes, investigate underlying dynamic regulatory molecular processes,
      and find ways to prevent these injury processes using peripheral cell models,
      e.g., red blood cells, lymphocytes and cultured skin fibroblasts. Information on
      the clinical implications of these processes are valuable for developing new and
      innovative therapeutic strategies for schizophrenia.

PMID- 9147490
TI  - Alpha ganglion cells of the rabbit retina lose antagonistic surround responses
      under dark adaptation.
AB  - Alpha ganglion cells from the midperiphery of the rabbit retina were recorded
      intracellularly under visual control, in a superfused everted eyecup, and labeled
      with HRP. Their physiology and large somata with broad dendritic arbors
      identified them as uniform populations of ON- and OFF-center alpha ganglion
      cells, which typically displayed transient/sustained light-evoked responses. When
      dark adapted, the light-evoked responses from both ON- and OFF-center alpha
      ganglion cells were more sustained than those generally seen under light-adapted
      conditions. During dark-adapted (scotopic) conditions, stimulation with dim full
      field illumination and small spots, either positioned over the soma or displaced
      450 microns from the soma, all elicited pure center responses. After light
      adaptation (photopic conditions), the displaced small spots that previously
      evoked center responses elicited antagonistic surround responses from both ON-
      and OFF-center cells. Thus, as originally described in cat retina (Barlow et al.,
      1957), the receptive-field organization of ganglion cells changed between dark
      and light adaptation, and an absence or presence of surround antagonism was
      indicative of scotopic versus photopic states.

PMID- 9147492
TI  - Impaired antioxidant defense at the onset of psychosis.
AB  - Previous studies found peripheral activities of antioxidant enzymes to be
      abnormal in schizophrenic patients. It is not understood whether this is integral
      to the disease process or a result of long-term treatment with neuroleptics. Red
      blood cell activities of three antioxidant enzymes--superoxide dismutase,
      glutathione peroxidase, and catalase--were therefore examined in 14 drug-naive,
      first episode patients with a diagnosis of schizophrenia or schizophreniform
      disorder and 10 normal subjects. The patients had an average duration of
      psychosis of 4.46 days (SD 2.5). Superoxide dismutase activity was significantly
      lower in patients than in normal controls, with no difference between the groups
      in activities of the other two enzymes. Lower superoxide dismutase activity was
      associated with deterioration of school functioning from childhood to early
      adolescence and a history of poorer school functioning during early adolescence.
      These findings indicate a compromised antioxidant defense at the onset of
      psychosis, and suggest that oxidative injury might contribute to adverse
      developmental events in the pathogenic cascade of schizophrenia.

PMID- 9147493
TI  - A study of enzymes involved in catecholamine metabolism in parents of patients
      with schizophrenia.
AB  - The concentrations of serum homovanillic acid (HVA), norepinephrine (NE),
      tyrosine (Tyr), phenylalanine (Phe) and tryptophan (Trp), and the activities of
      serum dopamine-beta-hydroxylase (DBH), platelet monoamine oxidase (MAO), and
      erythrocyte catechol-O-methyl transferase (COMT) were measured in 68 healthy
      parents who had schizophrenic offspring. The results show a significant
      correlation between the parents of schizophrenic patients in serum HVA (r=0.38,
      n=34, p<0.05), NE (r=0.40, n=33, p<0.02), Phe (r=0.44, n=34, p<0.0l), Tyr
      (r=0.43, n = 34, p <0.02) and DBH activity (r=0.51, n = 30, p <0.005), but do not
      show a significant correlation in erythrocyte COMT (r=0.01, n=27), platelet MAO
      (r=0.04, n=23) or serum Trp (r=0.10, n=34). There were no significant
      correlations in these measurements between randomly matched parents. The present
      study suggests that both parental sides of schizophrenic patients are likely to
      have similar alleles associated with the catecholamine pathway, and their ill
      offspring may possess a double dose of the schizophrenogenic alleles.

PMID- 9147494
TI  - Family history of autoimmune diseases in psychosis.
AB  - The mothers of 101 psychotic patients and 116 normal controls were interviewed
      using a semi-structured questionnaire designed to determine the presence or
      absence of autoimmune disorders in first degree relatives of the probands.
      Thyrotoxicosis and insulin-dependent diabetes mellitus were significantly more
      common in the relatives of the psychotic patients than in the control relatives;
      in particular thyrotoxicosis was more frequent in the mothers of patients (11%)
      than the mothers of controls (2.6%). None of the examined characteristics of the
      patients, including RDC-diagnosis, family history of psychosis, age at onset of
      psychosis and winter birth, was predictive of thyrotoxicosis and insulin
      dependent diabetes mellitus in relatives.

PMID- 9147495
TI  - Cerebral metabolic activity correlates of subsyndromes in chronic schizophrenia.
AB  - Seventy-nine patients with schizophrenia and 47 healthy controls received
      positron-emission tomography (PET) with 18F-2-deoxyglucose uptake while executing
      the Continuous Performance Test (CPT). Patients had been off all psychoactive
      medication for at least four weeks. Patients' symptoms were assessed with the
      Brief Psychiatric Rating Scale and factor scale scores were obtained. These
      scores were used in cluster analysis to identify patients with predominantly
      delusional, negative, disorganized, and remitted symptoms. To address the
      interconnective nature of cerebral functioning, regions of interest were defined
      on the basis of the results of a factor analysis of metabolic rate in selected
      brain regions. This procedure identified six cortical and eight subcortical
      region of interest factors. Metabolic rate factor scale scores were compared
      between the patients' clusters and the healthy controls. The delusional cluster
      showed a significantly reduced hippocampal activity, while the negative symptoms
      cluster presented with a prominent hypofrontality and significantly increased
      left temporal cortex values. Concurrently, both clusters were associated with a
      decreased activity on the factor 'anterior cingulum and medial frontal gyrus'.
      The disorganized cluster was characterized by a significant overactivity in the
      parietal cortex and motor strip and a decreased activity in the corpus callosum.
      The subsyndromes of chronic schizophrenia are therefore characterized by deviant
      patterns of cerebral activity rather than deficits in a single location.

PMID- 9147496
TI  - Proton magnetic resonance spectroscopy of the temporal lobes in schizophrenics
      and normal controls.
AB  - Previous research has found structural and functional abnormalities in the
      temporal lobes of schizophrenic patients, often with greater impairment on the
      left side. This study applied proton MRS to both right and left temporal lobes of
      schizophrenic patients and normal control subjects. Reductions in the NAA/Cr
      ratio were found bilaterally for schizophrenic patients as compared to normal
      controls, and may be associated with reduced neuronal integrity. These results
      strengthen the evidence for biochemical abnormalities in the temporal lobes in
      schizophrenia.

PMID- 9147497
TI  - Symptoms, cognitive and social functioning in recent-onset schizophrenia: a
      longitudinal study.
AB  - The relationships among symptoms, cognitive functioning and social functioning
      were investigated in patients with schizophrenia over a period of 15 months.
      Patients with a mood disorder, a normal control group and a sample of parents of
      the schizophrenic patients also completed the cognitive tests. In the
      schizophrenia sample, only disorganisation was correlated with cognitive
      performance, which was interpreted as further evidence that disorganisation is a
      separate symptom dimension of schizophrenia. Against expectations, with two of
      three measurements no significant correlations were found between negative
      symptoms and cognitive performance. With these two measurements, however, a
      curvilinear association between negative symptoms and cognitive performance was
      observed, suggesting that negative symptoms are not a unitary concept. Finally,
      tentative evidence could be obtained for speed of information processing and
      selective attention as markers for vulnerability, although the latter is not
      specific for schizophrenia.

PMID- 9147498
TI  - A study of the interrelationship between and comparative interrater reliability
      of the SAPS, SANS and PANSS.
AB  - We assessed the comparative interrater reliability of the SANS/SAPS and PANSS as
      measures of symptomatology in schizophrenia and also examined the
      interrelationship between scores on these instruments. Two experienced raters
      used these Scales to assess positive and negative symptoms in a group of 85
      patients with a DSM III-R diagnosis of schizophrenia. Ratings were based on
      structured clinical interviews, review of case notes and consultation with staff
      familiar with the patients. Comparable levels of interrater reliability were
      found for each system of measuring symptomatology, but levels of interrater
      reliability were on the whole lower than have been reported in the past. There
      were high correlations between overall indices of positive and negative
      symptomatology derived from the two measurement systems.

PMID- 9147499
TI  - [Amphotericin B. Lipid complex versus liposomes. Which, why, when?].

PMID- 9147500
TI  - [Cotrimoxazole plus rifampicin in the treatment of staphylococcal osteoarticular
      infection].
AB  - OBJECTIVE: To evaluate the efficacy and safety of cotrimoxazol plus rifampicin in
      staphylococcal osteoarticular infection. METHOD: Open, non-comparative study of
      adult hospitalized patients with documented staphylococcal bone infection.
      RESULTS: From Feb 1989 to Dec 1993 28 episodes of staphylococcal bone infection
      were treated in 14 men and 13 women; the mean age was 48 +/- 21 years (range, 11
      84). They received cotrimoxazol (7 mg/kg/day of trimethoprim) plus rifampicin
      (600-1200 mg/day), both orally, every 8 to 12 h with a mean duration of treatment
      of 34.2 +/- 8.2 days (range, 21 to 55 days). This antibiotic regimen was
      initiated at the same time that appropriate surgery for each specific condition
      was undertaken. Diagnoses were postsurgical osteomyelitis (10 cases), infected
      total hip prostheses (4 cases, one with 2 episodes), osteomyelitis secondary to
      external pin fixation (5 cases), soft tissue infections linked to orthopedic
      implants (3 cases), two cases of metatarsal osteomyelitis (one diabetic foot and
      one patient with polineuropathy), and one case each of chronic osteomyelitis of
      femur, hematogenous lumbar spondylitis and posttraumatic osteomyelitis. Four
      patients had bacteremia. The duration of the infection, prior to surgery was less
      than one month in 12 episodes, 1 month to 2 years in 14, and in 2 cases, of 10
      and 13 years, respectively. In 23 episodes the causal agent was Staphylococcus
      aureus and in 5 cases it was coagulase-negative staphylococci. Patients had
      received previous parenteral therapy with other antimicrobials during 2-40 days
      (X: 18.6 +/- 10.2 days). All patients but one had resolution of the infection and
      are currently asymptomatic 6 months to 5 years posttreatment in the 21 evaluable
      cases (X: 38 +/- 13.1 months). Five patients had adverse effects secondary to the
      antibiotic combination and in three these were severe enough to discontinue the
      antimicrobials. In no case of the 11 patients with post-treatment control
      cultures were staphylococci recovered from the wound. CONCLUSIONS: The
      combination of cotrimoxazole plus rifampicin, both given orally, was highly
      effective in this selected group of patients. This combination should be
      considered as a useful alternative therapy of staphylococcal bone infection and
      deserves further study.

PMID- 9147501
TI  - [Detection of low-avidity IgG antibodies in the diagnosis of primary acute
      infection by hepatitis C virus].
AB  - BACKGROUND: Differential diagnosis of the acute primary infection by hepatitis C
      virus (HCV) from reactivations and reinfections presents specific problems,
      especially among patients with impaired humoral immunity. the IgG avidity assay
      might contribute to resolve these problems. METHODS: A simple modification of a
      commercial enzyme immunoassay, allowing evaluation of the avidity of IgG antibody
      to HCV, was developed and evaluated on a part of 37 serum samples from 14
      patients with acute primary infection or reinfection by HCV and 12 samples from
      12 seropositive patients lacking evidence of acute infection Eight of the former
      14 had impaired ability for antibody response. RESULTS: The method rendered high
      percentages of reduction of the antibody signal in samples from acute primary
      infections taken within two months from onset and significantly lower percentages
      in samples from reinfections or patients without evidence of acute infection
      (mean value: 90 degrees C Vs 43% and 25%, respectively. The mean duration of the
      low-avidity IgG antibody was around six months, but showed wide variations
      depending on the patient. CONCLUSIONS: Detection of low-avidity IgG antibody to
      HCV is easy to perform and may help the study of the HCV infection in some
      patients. Every method should, however, be carefully validated before using with
      diagnostic purposes.

PMID- 9147502
TI  - [Pulmonary nocardiosis: presentation of 3 clinical cases].
AB  - INTRODUCTION: Nocardiosis is an infectious disease that frequently involves to
      the respiratory tract. Nocardia asteroides is the predominant human pathogen.
      Nocardiosis is difficult to diagnose and that's why its incidence is not well
      established. CASES: Three cases diagnosed in a Pneumology Section are reported.
      None of them was affected by AIDS and all of them were initially diagnosed from
      bronchopneumonia. Empirical antibiotherapy was initiated and because of the
      unsatisfactory progress, bronchoscopy was performed in all cases and in one case
      a transthoracic puncture was made. Nocardia spp. was then isolated and this let
      to began with a specific treatment. All the patients progress satisfactorily in
      their respiratory infection. DISCUSSION: Although there are usually factors that
      predispose to nocardiosis, it can also occur in absence of these, as it happened
      in one of report patients. The clinical and radiological manifestations are not,
      in many cases enough to reach the diagnosis. Thus germ isolation is very
      important, and invasive procedures are often essential to obtain a quality
      samples to cultivate. Sulfonamides were considered drugs of choice, but nowadays,
      many authors propose trimethoprim-sulfamethoxazole. Imipenem, amikacin have also
      proved to be effective.

PMID- 9147503
TI  - [Prevalence of antimicrobial resistance in enterococci isolated from blood in
      Madrid (1994-1995)].
AB  - BACKGROUND: The aim of this study was to evaluate the antimicrobial resistance of
      enterococci isolated from blood samples in three hospitals in Madrid (Spain) from
      1994 to 1995. METHODS: One hundred strains, 83 Enterococcus faecalis, 15 E.
      faecium, and 2 E. durans, isolated from January 1994 to April 1995 were studied.
      The minimum inhibitory concentrations (MIC) of 11 antimicrobians were determined
      by the agar dilution method. RESULTS: Four percent of the strains were resistant
      to ampicillin and 7% to penicillin. Ninety-two percent were sensitive to
      vancomycin. The percentage of strains with a high level of resistance (HLR) to
      some aminoglucoside was 60%. HLR was observed to gentamycin in 41%, to
      streptomycin in 46% and to kanamycin in 58% of the strains. Half of the isolates
      were resistant to the fluoroquinolones tested. HLR was significantly associated
      with aminoglucosides with HLR (MIC > or = 16 mg/l) to fluoroquinolones in the
      strains studied (p < 0.001). CONCLUSIONS: The incidence of resistance to
      ampicillin and vancomycin is low and very high to aminoglucosides and
      fluoroquinolones. There is also a very significant association between HLR to
      fluoroquinolones and HLR to aminoglucosides.

PMID- 9147504
TI  - [Propionibacterium acnes infection in patients with CSF shunts].
AB  - BACKGROUND AND METHODS: Propionibacterium acnes is a common inhabitant of human
      skin rarely associated with clinical disease. However it has been recognized as a
      cause of shunt and postneurosurgical infections. From January 1992 to June 1995,
      5,947 cerebrospinal fluid (CSF) samples were cultured in our laboratory. We
      carried out a clinical-epidemiological study in patients where P. acnes was
      isolated from CSF. RESULTS: P, acnes was isolated from 11 CSF samples which
      corresponded to 7 episodes of shunt infection in 6 patients. Five were men; the
      mean age was 28.5 years. The mean time of onset of infection after the last shunt
      manipulation was 104 weeks. All of them presented symptomatology associated with
      infection. All episodes but one, where P. acnes was considered to be a
      contaminant, were treated with systemic and intraventricular antibiotic therapy
      and complete shunt removal. Four patients made an uneventful recovery and two
      patients died due to causes not directly related with the infection. CONCLUSIONS:
      P. acnes is frequently isolated in patients with shunt infections. Its isolation
      must be seriously considered not viewed as a contaminant without an exhaustive
      investigation.

PMID- 9147505
TI  - [Cerebral SPECT with thallium-201 in the differential diagnosis of focal cerebral
      lesions in patients with AIDS].
AB  - BACKGROUND: The aim of this study was to analyze the usefulness of cerebral SPECT
      with thallium-201 in patients with the acquired human immunodeficiency syndrome
      (AIDS) and focal cerebral lesions. METHODS: Six patients with AIDS and focal
      cerebral lesions in whom a cerebral SPECT was performed with thallium-201 are
      described. Treatment was initiated with antiToxoplasma drugs in all patients. The
      clinical response, serology for positive toxoplasma and radiologic improvement
      were criteria for the diagnosis of encephalitis by Toxoplasma. In the remaining
      cases, cerebral biopsy and/or necropsy study were carried out. RESULTS: In the 2
      patients in whom cerebral SPECT demonstrated enhancement of the lesion, the
      pathologic diagnosis was cerebral lymphoma. Of the 4 remaining cases in whom no
      enhancement was observed, three corresponded to cerebral toxoplasmosis and one to
      progressive multifocal leucoencephalopathy. CONCLUSIONS: Cerebral SPECT with
      thallium-201 is a simple, specific and useful technique for the differentiation
      of primary cerebral lymphoma from the remaining inflammatory cerebral lesions
      which may be present in AIDS patients.

PMID- 9147506
TI  - [Microbiological diagnosis of rickettsial infections].

PMID- 9147507
TI  - [Erythematous papules in an adult woman].

PMID- 9147508
TI  - [Fever and pulmonary nodules in patients with HIV infection].

PMID- 9147509
TI  - [Isolation of Campylobacter sputorum biovar sputorum from a bed sore].

PMID- 9147510
TI  - [Rhabdomyolysis associated with Legionella pneumophila pneumonia].

PMID- 9147511
TI  - [Conjunctivitis caused by Aeromonas hydrophila].

PMID- 9147512
TI  - [Psoas abscess secondary to brucellar sacroiliitis. Resolution after conservative
      treatment].

PMID- 9147513
TI  - [Efficacy of an indirect immunofluorescence technique in the rapid diagnosis of
      parainfluenza virus type 3 infection].

PMID- 9147514
TI  - [Pulmonary infection by Mycobacterium malmoense in a patient with AIDS].

PMID- 9147515
TI  - [Infection by Bordetella bronchiseptica in patients with AIDS].

PMID- 9147516
TI  - [Change in susceptibility to measles].

PMID- 9147517
TI  - [Comparative study of the protective role of the vaccine against Haemophilus
      influenzae type b and partial splenectomy in an experimental model].
AB  - BACKGROUND: Although the vaccine against Haemophilus influenzae type b has
      demonstrated its efficacy in children, this bacteria continues to be a cause or
      overwhelming sepsis in splenetomized patients. METHODS: To compare the degree of
      protection provided by partial splenectomy and the conjugated diptheria toxoid
      vaccine against H. influenzae type b, the bacteremia generated 24, 48 and 96
      hours after intravenous inoculation with this bacteria at concentrations of 5 x
      10(14), 5 x 10(13) and 5 x 10(12) colony-forming units was assessed in rats
      subjected to total splenectomy, with and without previous vaccination, to partial
      splenectomy or to sham operation. RESULTS: With respect to both the proportion of
      positive blood cultures and the concentration of H. influenzae in the blood
      stream, the sham-operated control rats and those vaccinated prior to splenectomy
      presented similar behaviors; the widest differences with respect to the latter
      two groups were found in the nonvaccinated total splenectomy rats, and the
      results with the partial splenectomy group fell between these two extremes.
      CONCLUSIONS: The protection of H. influenzae type b vaccine against infection is
      equivalent to that provided by the intact spleen for inoculum concentrations of 5
      x 10(13) colony-forming units and less. Thus, the possibility of its systematic
      use in asplenic patients should be considered. The protection provided by the
      remnant spleen following 50% splenectomy is intermediate between those observed
      with eusplenia and with asplenia. These results suggest that when partial
      splenectomy is to be performed in normal spleen, the attempt should be made to
      conserve as much of the organ as possible.

PMID- 9147518
TI  - [Mandibular actinomycosis caused by Actinomyces odontolyticus].

PMID- 9147519
TI  - [Amphotericin B--lipid complex].

PMID- 9147520
TI  - Modification of mutant K-ras gene expression in non-small cell lung cancer
      (NSCLC).

PMID- 9147521
TI  - Time and flow study results before and after installation of a hospital
      information system and radiology information system and before clinical use of a
      picture archiving and communication system.
AB  - The effectiveness of a hospital information system (HIS) and a radiological
      information system (RIS) was evaluated to optimize preparation for the planned
      full clinical operation of a picture archiving and communication system (PACS),
      which is now linked experimentally to the HIS and the RIS. One thousand IC
      (integrated circuit) cards were used for time studies and flow studies in the
      hospital. Measurements were performed on image examination order entry, image
      examination, reporting, and image delivery times. Even though after the HIS and
      the RIS operation only a small amount of time savings were realized in each time
      fraction component, such as in the patient movement time, examination time, and
      film delivery time, the total turn-around time was shortened markedly, by more
      than 23 hours on average. It was verified that the HIS and the RIS was beneficial
      in the outpatient clinics of the orthopedic department. Our method of measurement
      employing IC cards before and after HIS and RIS operations can be applied in
      other hospitals.

PMID- 9147522
TI  - Direct reconstruction of single-photon emission computed tomography images using
      retained matrix elements.
AB  - In clinical applications, two methods of single-photon emission computed
      tomography (SPECT) reconstruction are widely used. These are filtered
      backprojection and iterative reconstruction. Filtered backprojection is fast and
      produces acceptable images. Iterative reconstruction is slow, but produces images
      of greater accuracy than backprojection. The authors sought to develop a method
      of SPECT reconstruction that would have the advantages of both established
      methods: close in speed to backprojection and with the accuracy of iterative
      reconstruction. This was accomplished by computing a direct solution to the set
      of linear equations governing SPECT reconstruction. We tested this method of
      SPECT reconstruction using a set of projections from a cold rod and sphere
      phantom. Direct reconstruction produced images having equivalent resolution to
      backprojected images, but with double the contrast ratio. The direct method
      required 10 seconds of computation per slice on a Macintosh Quadra 950 (Apple
      Computer; Cupertin, CA), significantly faster than most iterative methods.

PMID- 9147523
TI  - A pilot study of eye movement during mammography interpretation: eyetracker
      results and workstation design implications.
AB  - Digital mammography can potentially improve mammography image and interpretation
      quality. On-line interpretation from a workstation may improve interpretation
      logistics and increase availability of comparison images. Interpretation of eight
      4k- x 5k-pixel mammograms on two to four 2k- x 2.5k-pixel monitors is problematic
      because of the time spent in choosing which images display on which monitors, and
      zooming and roaming on individual images that are too large to display completely
      at full resolution. The authors used an eyetracker to measure radiologists
      viewing behavior during mammography interpretation with film on a viewbox. It was
      observed that a significant portion of the mammographers' time is spent viewing
      "comparison pairs" (typically two or more comparisons per case), such as the left
      mediolateral and craniocaudal images or old and new images. From the eyetracker
      measurements, we estimated that the number of image display, roam, and zoom
      operations decreases from an average of 64 for one monitor to 31 for four
      monitors, with the largest change going from one to two monitors. We also show
      that fewer monitors with a faster response time is superior to more monitors with
      a slower response time. Finally, the authors demonstrate the applicability of
      time-motion analysis to mammographic workstation design.

PMID- 9147524
TI  - A multimedia database system for thermal ablation therapy of brain tumors.
AB  - A prototype multimedia medical database is described for supporting thermal
      ablation therapy of brain tumors. Its design is motivated by the major need to
      manage and access multimedia information on the progress and reaction of tumors
      to various therapy protocols. The database links images to patient data in a way
      that permits the use to view and query medical information using alphanumeric,
      temporal, and feature-based predicates. Visualization programs permit the user to
      view or annotate the query results in various ways. These results support the
      wide variety of data types and presentation methods required by neuroradiologists
      to manage thermal ablation therapy data. The database satisfactorily meets the
      requirements defined by thermal ablation therapy. A similar approach is being
      undertaken for supporting different therapies of other types of tumors, thus
      showing the generality of our approach.

PMID- 9147525
TI  - Control method for preloading with priority information in an integrated
      radiology information system/picture archiving and communication system.
AB  - More than 10 years has passed since the concept of picture archiving and
      communication systems (PACS) was first proposed. A great deal of effort has been
      expended to make PACS suitable for routine use in clinical settings, but only a
      few systems are currently used in this manner. A major reason is the lack of the
      assurance of throughput equivalent to that of a conventional system based on
      order sheets and analog films. In this report, two techniques to increase
      throughput have been introduced and studied. The first is the preloading of data
      elements from the various information systems and the PACS. The second is the use
      of the priority information to rank order the examinations placed on the list for
      interpretation. We have applied these techniques to an actual system and have
      measured the distribution of time for processing examinations. These two
      techniques appear to make PACS useful in routine practice because most of the
      urgent cases were interpreted within the target time of 40 minutes.

PMID- 9147526
TI  - Detection of interstitial lung abnormalities on picture archive and communication
      system video monitors.
AB  - The purpose of this study was to compare the detection of interstitial lung
      abnormalities on video display workstation monitors between radiologists
      experienced with video image interpretation and radiologists who lack this
      experience. Twenty-four patients with interstitial lung abnormalities documented
      by high-resolution computed tomography (HRCT) and lung biopsy, and 26 control
      patients with no history of pulmonary disease or a normal HRCT and normal chest
      radiographs were studied. Images were acquired using storage phosphor digital
      radiography and displayed on 1,640 x 2,048 pixel resolution video monitors. Five
      board-certified radiologists evaluated the images in a blinded and randomized
      manner by using a six-point presence of abnormality grading scale. Three
      radiologists were from 1 to 4 years out of residency and considered to be
      experienced workstation monitor readers with between 1 to 3 years of video
      monitor image interpretation. For the inexperienced readers, one radiologist had
      no prior experience with reading images from a video monitor and was direct out
      of residency, and the other radiologist had less than 4 months of intermittent
      exposure and was 1 year out of residency. Sensitivity and specificity were
      determined for individual readers. Positive predictive values, negative
      predictive values, accuracy, and receiver-operating curves were also generated. A
      comparison was made between experienced and inexperienced readers. For readers
      experienced with video monitor image interpretation, the sensitivity ranged from
      87.5% to 92%, specificity from 69% to 92%, positive predictive value (PPV) from
      73% to 87.5%, negative predictive value (NPV) from 87% to 90%, and accuracy from
      80% to 88%. For inexperienced readers, these values were sensitivity 58%,
      specificity 50% to 65%, PPV 52% to 61%, NPV 56.5% to 63%, and accuracy 54% to
      62%. Comparing image interpretation between experienced and inexperienced
      readers, there were statistically significant differences for sensitivity (P <
      .01), specificity (P < .01), PPV (P < .05), NPV (P < .05), accuracy (P < .05),
      and area under the receiver operator curve (Az) (P < .01). Within the respective
      experienced and inexperienced groups, no statistical significant differences were
      present. Our results show that digitally acquired chest radiographs displayed on
      high-resolution workstation monitors are adequate for the detection of
      interstitial lung abnormalities when the images are interpreted by radiologists
      experienced with video image interpretation. Radiologists inexperienced with
      video monitor image interpretation, however, cannot reliably interpret images for
      the detection of interstitial lung abnormalities.

PMID- 9147527
TI  - Processes involved in reading imaging studies: workflow analysis and implications
      for workstation development.
AB  - Software development for imaging workstations has lagged behind hardware
      availability. To guide development and to analyze work flow involved in
      interpretation of cross-sectional imaging studies, we assessed the cognitive and
      physical processes. We observed the performance and interpretation of body
      computed tomography (CT) scans and recorded the events that occurred during this
      process. We studied work flow using a bottleneck analysis. Twenty-four of a total
      of 54 cases (44%) involved comparing the images with those of prior scans. Forty
      seven of 54 scans (87%) were viewed using windows other than soft tissue, or
      compared with precontrast scans. In 46 cases (85%), the interpretation stopped to
      return to a previous level for review. Measurement of lesions was performed in 24
      of 54 (44%) cases, and in 15 (63%) of these cases, measurements were taken of
      lesions on old studies for comparison. Interpretation was interrupted in 14 of 54
      cases (26%) by referring clinicians desiring consultation. The work flow analysis
      showed film folder retrieval by the film room to be the bottleneck for
      interpretation by film. For picture archiving and communication system (PACS)
      reading, the CT examination itself proved to be the bottleneck. We conclude that
      workstations for CT interpretation should facilitate movement within scans,
      comparison with prior examinations, and measuring lesions on these scans.
      Workstation design should consider means of optimizing time currently not used
      between interpretation sessions, minimizing interruptions and providing more
      automated functions currently requiring physician interaction.

PMID- 9147528
TI  - [Stability of vitamins in parenteral nutrition: a comparison of multi-layer and
      uni-layer bags].
AB  - The goal of this study was to compare vitamin A, E, C, B12, B2 and folic acid
      concentrations in parenteral nutrition solutions in multilayer and single layer
      EVA bags. Two different bag trade marks were used: Bexen and Miramed. We measured
      vitamin concentrations at 24 hours, the fifth and seventh day after refrigerated
      storage and the eighth day after 24 hours at room temperature. Trace-element and
      temperature influence were studied. Vitamins A, E, B12, B2 and folic acid had a
      similar behaviour with multi-layer and one-layer bags. No differences were
      observed between solutions with and without trace-elements. The concentrations
      remained within acceptable ranges. We observed a clear decrease of vitamin C,
      that can be avoided with the use of multilayer bags. These bags can be useful in
      home parenteral nutrition or when vitamins cannot be added immediately before its
      administration. An important loss of vitamin A was also detected in parenteral
      nutrition solutions without lipids, both in multilayer and single layer bags,
      despite photoprotection and refrigeration.

PMID- 9147530
TI  - [Incidence of malnutrition in surgical departments of the Reina Sofia Hospital of
      Cordoba].
AB  - We conducted a prospective study of the incidence of malnutrition in the surgical
      departments of the Reina Sofia University Hospital, on a total of 329 patients at
      the time of admittance (154 women and 175 men). As was denounced by Bristian more
      than 20 years ago, more than 50% of the patients presented some form of
      malnutrition. There are a series of factors, detected by the Chi2 test, which are
      as divers as sex, marital status, level of education, profession, smoker or
      chronic medication user, which are of influence on the nutritional status of the
      patients. The type of malnutrition is conditioned by the marital status, the job
      situation, the nature of the pathology, or the use of tobacco. Malnutrition still
      exists in developed countries, induced by many factors, and it is often found in
      the hospitals, which is even worse.

PMID- 9147529
TI  - [Decrease of the incidence of sepsis syndrome after early enteral nutrition of
      patients with severe burns].
AB  - The objective of this study was to evaluate the effect of early enteral nutrition
      on the incidence of the septic syndrome as well as its tolerance, in patients
      with severe burns. We retrospectively studied 64 patients older than 15 years of
      age, with a greater than 20% burned body surface area. They were divided into 2
      groups as a function of the time elapsed between the beginning of Enteral
      Nutrition and the time of the burning: 23 patients were given Enteral Nutrition
      within 24 hours after the burn, and in 41 patients the enteral nutrition was
      started later than 24 hours after sustaining the thermal injury. Both groups were
      similar with respect to age, sex, percentage of 2nd and 3rd degree burns,
      incidence of inhalation, and deaths. All patients received the Enteral Nutrition
      through a nasogastric tube, with administration of a polymeric, hyperprotein and
      hypocaloric formula through a continuous infusion pump. In our study we saw a
      reduction of the incidence of the septic syndrome in the patients who received
      early enteral Nutrition (26%; 6 patients of a total of 23), with respect to those
      who did non receive early Enteral Nutrition (54%; 22 patients of a total of 41),
      with a statistical significance of p > 0.05. There were no differences between
      both groups with respect to the digestive tolerance to Enteral Nutrition. From
      our study we can deduce that early Enteral Nutrition reduces the incidence of
      septic complications, without this increasing the digestive intolerance to the
      same.

PMID- 9147531
TI  - [Description of a computer program and results of its application to the follow
      up of enteral nutrition].
AB  - Computerization has been introduced little by little in the different activities
      which take place in a department of pharmacy, due to the fact that it means an
      increased agility of the tasks to be performed as well as an improvement of the
      care and managerial quality. In our hospital, the department of pharmacy makes up
      enteral nutrition units, and it participates in the follow up and control of the
      patients with this type of nutrition through a computer program designed for this
      purpose. The objective of the present study is to describe this computerized
      program as well as the results obtained by its application. The enteral nutrition
      computer program is made up of two data bases which are indexed between each
      other: that of daily follow up of the enteral nutrition prescriptions, and that
      of the follow up of the patients who have been given this nutritional support. In
      this way it allows us to obtain identification labels and consumption listings.
      During a two year period a total of 632 enteral nutrition treatments were given.
      The department with the greatest number of prescriptions was internal medicine
      (187, 29.5%). The polymeric diets were the most frequently used (435, 68.7%). The
      have mainly been used as a supplement to a hospital kitchen diet (149, 41.8%).
      The oral administration was the most frequent route of administration (331,
      52.4%). The main reason for not implementing the nutrition was refusal by the
      patient (114, 38%). The computer program allows greater agility of the circuit
      which in our hospital generates the preparation of the enteral nutrition
      formulations, which are made up in the Department of Pharmacy, and given the
      large number of variables which this implies, this means a quality guarantee in
      the preparation and follow up of the patients with enteral nutrition.

PMID- 9147532
TI  - [Nutritive, nutrimental or ... nutritional. Some reflections on the growing
      deterioration of the medical language].

PMID- 9147533
TI  - [Spanish consensus on the preparation of parenteral nutrient mixtures. National
      Work Group "Pharmaceutic aspects of nutrition"].

PMID- 9147535
TI  - [Parenteral nutrition and gastric emptying].

PMID- 9147534
TI  - [Domiciliary artificial nutrition. Annual Report 1994. NADYA Group].
AB  - The NADYA Group, integrated in the Spanish Society of Parenteral and Enteral
      Nutrition (SENPE), and made up of professionals dedicated to Artificial
      Nutrition, and specifically, to Artificial Nutrition in the home, annually
      undertakes the task of collecting data on diagnosis, type of support, follow up
      characteristics, complications, and quality of life, of patients included in
      programs of at home artificial nutrition in Spain. In the Annual Register
      corresponding to 1994, 17 hospitality groups have participated, providing 369
      patients with Home Enteral Nutrition, and 30 with Home Parenteral Nutrition. Home
      Enteral Nutrition is mainly applied in patients with neoplasias (36%) or
      neurological alterations (35%). The most commonly used access route in the
      nasogastric tube, although there is an observed increase in the application of
      Percutaneous Gastrostomies (21%) in relation to previous data of the Spanish
      population. There is an observed complications index of 0.07 episodes/patient
      year, a mortality of 30% (neoplasias) and 20% (neurological alterations), and low
      rehabilitation indexes in this group. In Home Parenteral Nutrition, post
      radiation enteritis, neoplasias, and mesenteric ischemia, are the main diagnostic
      groups. The majority of the patients have a tunneled tube (63%), with 37% using
      an implanted tube. With an index of hospitalizations of 0.83 hospitalizations/
      patient-year, catheter septicemia justifies the majority of the re
      hospitalizations derived from nutritional treatment (0.56
      hospitalizations/patient-year), note the mortality of 37%. There are complete
      rehabilitations, continuing the previously normal activity in 80% of the cases.

PMID- 9147536
TI  - [Vena cava perforation by a catheter].

PMID- 9147538
TI  - Peritoneal dialysis--year 2010.

PMID- 9147537
TI  - [Magnesium: metabolism and requirements].
AB  - Magnesium is an important element in health and in disease, it is the organism's
      second most abundant intracellular cation, after potassium, and it is the main
      divalent intracellular cation. Its metabolic importance is well known, as it has
      been identified as a cofactor in more than 300 enzymatic reactions which affect
      the energetic metabolism, and the synthesis of proteins and nucleic acids,
      Hypomagnesemia is a frequent finding in hospitalized patients, even more so when
      the patients are critical (+/-65%). Although low serum levels of magnesium imply
      the presence of intracellular depletion, normal serum magnesium levels may be
      present in situations of intracellular magnesium depletion, with important
      clinical repercussions. Keeping in mind that only 1% of the body's magnesium is
      in the extracellular fluid, the serum magnesium levels may not adequately reflect
      the situation, which is why techniques have been proposed which determine the
      intracellular concentracion. The identification of the patients who may
      potentially present a magnesium depletion, requires a clear knowledge of the risk
      factors associated with magnesium deficiency: poorly controlled diabetes
      mellitus, excessive alcohol intake, severe diarrhea, important steatorrhea, and
      the use of drugs which favor their renal excretion. The present review gives an
      up date of the most frequent causes of magnesium deficits, giving a series of
      practical recommendations to prevent this situation, and to undertake a correct
      replacement therapy. Finally, and although hypermagnesemia appears in a reduced
      number of circumstances, the presence of kidney failure of diverse etiology, as
      well as the broadening of the indications of magnesium salts, have increased its
      incidence, which is why special emphasis is made in this section.

PMID- 9147539
TI  - The Internet and peritoneal dialysis.

PMID- 9147540
TI  - Do we have an objective method to determine compliance with the peritoneal
      dialysis prescription?

PMID- 9147541
TI  - Vancomycin revisited.

PMID- 9147542
TI  - Large mesothelial cells in peritoneal dialysis: a sign of degeneration or
      adaptation?

PMID- 9147543
TI  - The "nearest capillary" hypothesis: a novel approach to peritoneal transport
      physiology.

PMID- 9147544
TI  - Preservation of residual renal function in maintenance dialysis patients.

PMID- 9147545
TI  - The removal index for evaluation of dialysis.
AB  - OBJECTIVES: To find an index of adequacy that takes into consideration the effect
      of the decreasing concentration of urea nitrogen in hemodialysis (HD) and can be
      used before treatments to quantitate the prescriptions with the same criterion
      for both HD and continuous ambulatory peritoneal dialysis (CAPD). DESIGN: The
      removal index was obtained through mathematical theories and then compared with
      the urea index (KT/V) values of the sample patients. PATIENTS: Thirty-two HD and
      21 CAPD patients were included. All patients were dialyzed with optimal urea
      index values and had been stable for at least one year. RESULTS: The removal
      index in HD (xi HD) for each dialysis was O.62 +/- 0.07, and the normalized
      removal index in CAPD (xi CAPD) was 0.59 +/- 0.11. There was no statistical
      significance. This result is consistent with the fact that no difference of
      morbidity or mortality exists between these two modalities. CONCLUSION: After
      mathematical manipulation, the removal index in HD can be presented in the form
      of the urea reduction ratio, which is a retrospective measure to estimate the
      performance of hemodialysis. This study implies that the removal index is able to
      facilitate the prescriptions for adequate dialysis. The removal index can also be
      used to explain the reason why the urea index values are always larger in HD than
      in CAPD.

PMID- 9147546
TI  - Fractional urea clearance estimates using two anthropometric formulas in
      continuous peritoneal dialysis: sex, height, and body composition differences.
AB  - OBJECTIVE: To compare estimates of urea volume (V) and KT/V obtained by the
      Watson and Hume anthropometric formulas, and to identify the similarities and
      differences between these estimates. DESIGN: Theoretical analysis applying wide
      variations in the determinants of anthropometric V (age, height, weight) in
      hypothetical women and men. Analysis of urea kinetic studies performed in
      patients on continuous peritoneal dialysis (CPD). SETTING: Four dialysis units in
      Albuquerque, two in Athens, and two in Thessaloniki. PARTICIPANTS: Three hundred
      and two CPD patients who had 440 urea kinetic studies. INTERVENTION: Standard
      urea clearance was performed by 24-hour collections of urine and drained
      dialysate followed by blood sampling. V was estimated by both the Watson and Hume
      formulas. MAIN OUTCOME MEASURES: Estimates of V and KT/V were compared separately
      in women and men by Student's t-test, linear regression, and limits of agreement
      (mean difference +/- 2 SD). The agreement of the KT/V estimates was also tested
      by the kappa ratio using a value of 1.70 weekly as the lowest acceptable K/TV.
      RESULTS: The theoretical analysis indicated important disagreement only in
      extreme variations from the ordinary in height and, to a lesser extent, weight.
      Differences due to height variation were pronounced only in hypothetical women.
      CPD patient findings were as follows: in women, Watson V and weekly KT/V were
      30.4 +/- 4.4 L and 2.10 +/- 0.61, respectively. Corresponding Hume estimates were
      30.3 +/- 5.4 Land 2.1 2 +/- 0.66, respectively. Corresponding estimates for men
      were 40.5 +/- 5.7 L and 1 .92 +/- 0.57 (Watson) plus 41.4 +/- 5.6 L and 1.88 +/-
      0.57 (Hume), respectively. By linear regression, KT/V(Hume) = -0.083 + 1.052
      (KT/V(Watson)), r = 0.961 (women); and KT/V(Hume) = -0.026 +/- 0.992
      (KT/V(Watson)), r = 0.985 (men). Limits of agreement were -1.41 L and 2.10 L for
      V, and -0.15 and 0.14 weekly for KT/V. In 94.3% of the cases, KT/V(Watson) and
      KT/V(Hume) agreed (both > 1 .70 or both < 1 .70 weekly). Kappa ratio was 0.875
      (excellent agreement). The concordant and discordant groups differed in height
      and degree of obesity, in agreement with the theoretical analysis. CONCLUSION:
      The Watson and Hume formulas provide similar estimates of V and KT/V in CPD
      patients. Differences may be noted only if women's height or, to a lesser extent,
      both sexes' weight is at a great variance with the ordinary values.

PMID- 9147547
TI  - An elevated ratio of measured to predicted creatinine production in CAPD patients
      is not a sensitive predictor of noncompliance with the dialysis prescription.
AB  - OBJECTIVE: To determine the effect a period of "intentional noncompliance" in
      stable continuous ambulatory peritoneal dialysis (CAPD) patients has on the ratio
      of measured to predicted creatinine generation. DESIGN: Prospective study that
      compares baseline to noncompliant periods in individual CAPD patients. PATIENTS:
      Nine chronic, stable CAPD patients. STUDY DESIGN: At baseline, measured
      creatinine production and adequacy parameters (KT/V, creatinine clearance, lean
      body mass, and protein equivalent of nitrogen appearance) were calculated from 24
      hour collections of dialysate and urine while patients were performing their
      routine dialysis prescriptions. After three days of intentional noncompliance
      (one less exchange/day) the patients repeated their 24-hour collections, again
      performing their routine number of exchanges. Measured creatinine production and
      adequacy parameters were again calculated. Predicted creatinine production for
      each patient was calculated from standard equations. All parameters at baseline
      were compared to corresponding parameters after intentional noncompliance.
      RESULTS: In all patients, except one where there was no change, there was a
      statistically significant increase in not only the ratio of measured to predicted
      creatinine production but also all other parameters. CONCLUSION: As suspected by
      previous investigators, this study suggests that one cause of an elevated ratio
      of measured to predicted creatinine production may be a recent period of
      noncompliance with the patient's dialysis prescription. However, these data
      suggest that an isolated ratio of measured to predicted creatinine generation is
      not a sensitive predictor of noncompliance with the peritoneal dialysis
      prescription.

PMID- 9147548
TI  - Comparison of measured and predicted creatinine excretion is an unreliable index
      of compliance in PD patients.
AB  - OBJECTIVE: To evaluate the use of the ratio of measured to predicted creatinine
      excretion as an index of compliance in peritoneal dialysis (PD) patients. DESIGN:
      A prospective analysis. SETTING: Academic teaching hospital dialysis unit.
      PATIENTS: Forty-three patients on PD. MEASUREMENTS: Creatinine excretion in daily
      dialysate and urine collections was measured on one occasion in 10 patients and
      on two occasions in 33 patients, and, after adding an estimate for extrarenal
      creatinine degradation, was divided by predicted creatinine excretion to give a
      creatinine excretion ratio, which has been proposed as an index of compliance
      with exchanges in PD patients. Values above 1.24 have been suggested to indicate
      noncompliance. Lean body mass was also estimated from creatinine excretion.
      RESULTS: The mean creatinine excretion ratio was 1.12, and 30% of patients had a
      value above 1.3. Only one patient admitted noncompliance. Studies on four
      consecutive days of guaranteed compliance in 7 patients with high ratios showed
      that creatinine excretion remained constant, suggesting that the patients were
      high creatinine producers rather than noncompliant. Creatinine excretion was
      stable when measured at intervals of days, but over months it tended to change
      markedly in many patients. Lean body mass estimations using creatinine excretion
      were low in most patients. CONCLUSION: Comparison of measured and predicted
      creatinine excretion is not a reliable indicator of noncompliance because many
      compliant patients consistently excrete more creatinine than predicted. The
      standard formulas were not validated in dialysis patients and underestimate
      creatinine excretion significantly in many PD patients. Existing estimates in the
      literature of noncompliance, using this methodology, may not be accurate. Better
      methods of detecting this problem are required.

PMID- 9147549
TI  - Peritoneal dialysate IgG/C3 levels do not predict susceptibility to peritonitis.
AB  - OBJECTIVE: To investigate the usefulness of dialysate IgG and C3 concentrations
      in predicting likelihood of developing peritonitis. DESIGN: Prospective,
      longitudinal, and comparative study. SETTING: Single university teaching hospital
      dialysis unit and outpatient clinic. PATIENTS: Thirty-four uremic patients were
      studied (20 males, 14 females: mean age 47.2, range 20-73 years). Monthly serum
      and overnight dialysate (eight- to eleven-hour dwell) samples were obtained for
      IgG and C3 estimations over the first six months of the study, and trimonthly
      samples were obtained thereafter. All patients performed exchanges using standard
      transfer sets (Baxter system II, Baxter Healthcare Ltd., Thetford, Norfolk,
      U.K.), used no hypertonic fluid (3.86%) for overnight exchanges, and were
      followed up for a minimum of 18 months. OUTCOME MEASURES: Dialysate and serum
      levels of IgG and C3; peritonitis episodes. RESULTS: Forty-five episodes of
      peritonitis occurred in 24 patients during the study period. We examined opsonin
      levels in the group as a whole, and then in two subgroups of patients: those who
      remained peritonitis-free throughout the study, and those who did not. There were
      no significant differences between IgG and C3 levels in the two groups at any
      time point, and large interpatient and intrapatient variation in levels were
      seen. CONCLUSION: Dialysate levels of IgG and C3 from the overnight dwell are not
      helpful in predicting the risk of developing continuous ambulatory peritoneal
      dialysis peritonitis in individual patients. No correlation was found between
      opsonin levels and onset of clinical peritonitis.

PMID- 9147550
TI  - Chronic induction of C-reactive protein by hemodialysis, but not by peritoneal
      dialysis therapy.
AB  - OBJECTIVE: Evaluation of the inflammatory activity in patients on chronic
      peritoneal dialysis (PD) and patients on chronic hemodialysis (HD) in comparison
      to patients with chronic renal insufficiency without dialysis treatment and
      healthy volunteers. DESIGN: Open, nonrandomized prospective study. SETTING:
      Nephrology Department, including HD and PD therapy in a university hospital.
      PATIENTS: Twenty-four patients on chronic PD,21 patients on chronic HD therapy
      using a cuprophan dialyzer,16 patients with chronic renal insufficiency without
      dialysis treatment, and 33 healthy volunteers; 8 additional patients before and
      after initiation of chronic HD therapy. All patients and controls were without
      infection or immunosuppressive therapy. MAIN OUTCOME MEASURES: As a marker of the
      inflammatory activity in the different patient groups, C-reactive protein (CRP)
      was measured serially using a sensitive, enzyme-linked, immunosorbent assay in
      order to detect values below the detection limit of standard assays. RESULTS:
      Patient groups had CRP levels higher than the normal controls (p < 0.01).
      Patients on HD had CRP levels significantly higher than PD patients (p < 0.01)
      whose levels were comparable to patients without dialysis therapy. Accordingly,
      longitudinal measurements before and after initiation of chronic HD showed a
      significant increase in CRP levels after the beginning of HD treatment (p <
      0.04). CONCLUSIONS: The results suggest that induction of the inflammatory
      activity is lower during PD compared to HD, since stimulation by the dialyzer
      membrane, dialysate buffer, or bacterial fragments in the dialysate is avoided.
      This observation might indicate a possible lower risk of long-term complications
      in patients with PD.

PMID- 9147551
TI  - Reduced lymphatic drainage of dialysate from the peritoneal cavity during acute
      peritonitis in sheep.
AB  - OBJECTIVES: The purpose of this study was to investigate the effects of acute
      peritonitis on lymphatic drainage of the peritoneal cavity in conscious sheep.
      DESIGN: Peritonitis was induced with the addition of 1% casein or 1% albumin to
      the dialysis solution. Thirty sheep (5 groups of 6) were used in this study. One
      group received 50 mL/kg intraperitoneal infusions of Dianeal 4.25% (486 mOsm/L);
      a second group received 1% casein-Dianeal 4.25% (493 mOsm/L); a third group
      received 1% albumin-Dianeal 4.25% (487 mOsm/L). In the fourth and fifth groups
      (controls and casein-injected) lymph was collected from the caudal mediastinal
      lymph node and the thoracic duct, both of which are involved in the lymphatic
      drainage of the peritoneal cavity (peritonitis induced with casein). (125)I-human
      serum albumin (25 mu CI) was added to the dialysate as the lymph flow marker.
      Lymph drainage was estimated from (1) the appearance of the intraperitoneally
      administered tracer in the blood; (2) the disappearance of the tracer from the
      peritoneal cavity; and (3) the recovery of tracer in lymph. RESULTS: In
      noncannulated animals the cumulative volume removed by lymphatics over 6 hours
      (based on tracer recovery in blood) was 10.5 +/- 1.0 mL/kg in control animals
      versus 5.0 +/- 0.6 mL/kg and 8.6 +/- 1.2 mL/kg in casein and albumin-infused
      sheep, respectively. The suggestion of decreased lymph drainage in peritonitis
      was supported by the cannulation experiments. While the cumulative fluid removed
      from the peritoneal cavity over 6 hours in caudal lymph was unaffected by
      peritonitis (3.8 +/- 0.4 mL/kg in controls vs 3.6 +/- 0.5 mL/kg in casein
      injected animals), peritonitis reduced flow into the thoracic duct from 3.0 +/-
      0.3 to 1.1 +/- 0.3 mL/kg. The sum of the volume removed in lymph in the
      cannulated preparations was 6.8 +/- 0.4 mL/kg in controls versus 4.7 +/- 0.5
      mL/kg in the peritonitis group. The total volume removed from the cavity
      (including an estimate of flow based on the residual recovery of tracer in blood)
      was reduced from 12.6 +/- 1.4 in controls to 7.8 +/- 0.6 mL/kg in the peritonitis
      sheep. In contrast, estimates of lymph drainage based on the disappearance of
      tracer from the peritoneal cavity suggested that lymph drainage increased (from
      16.6 +/- 1.6 mL/kg in controls to 17.8 +/- 1.5 mL/kg and 25.5 +/- 1.7 mL/kg in
      the casein and albumin groups, respectively, in noncannulated animals and from
      15.3 +/- 1.4 mL/kg in controls to 25.0 +/-1.7 mL/kg in the cannulated group). In
      both noncannulated and cannulated sheep the total recovery of tracer was less in
      the peritonitis groups. CONCLUSIONS: These studies demonstrated that lymph
      drainage of the peritoneal space was decreased in a casein peritonitis model. The
      decrease in lymph drainage is most obvious in the visceral pathway leading to the
      thoracic duct; however, diaphragmatic drainage into the right lymph duct may also
      be inhibited. The disappearance of tracer from the peritoneal cavity was elevated
      during peritonitis. Tracer disappearance has been used to estimate lymph
      drainage, but this approach suggested, incorrectly, that lymph flow had
      increased.

PMID- 9147552
TI  - Comparison of intraperitoneal administration of two preparations of vancomycin in
      causing chemical peritonitis.

PMID- 9147553
TI  - IV vancomycin-oral ciprofloxacin: a safe and efficient therapeutic protocol for
      CAPD peritonitis (preliminary report).

PMID- 9147554
TI  - Gastric antral vascular ectasia in a patient on hemodialysis improved with CAPD.

PMID- 9147555
TI  - Exit-site colonization and subsequent peritonitis by Pseudomonas aeruginosa in a
      patient on CAPD.

PMID- 9147556
TI  - Hemoperitoneum due to carcinomatosis in the liver of a CAPD patient.

PMID- 9147557
TI  - Diameter of the inferior vena cava as an index of dry weight in patients
      undergoing CAPD.

PMID- 9147558
TI  - Inadvertent intravesical insertion of a Tenckhoff catheter.

PMID- 9147559
TI  - Malassezia furfur: a possible cause of culture-negative CAPD peritonitis.

PMID- 9147560
TI  - Saccharomyces cerevisiae peritonitis complicating CAPD.

PMID- 9147561
TI  - Comparisons of the swan neck and Tenckhoff catheters.

PMID- 9147562
TI  - Varicella pneumonitis in a child undergoing CAPD.

PMID- 9147564
TI  - Literature. January-February 1996.

PMID- 9147563
TI  - Peritoneal dialysis case forum: a patient with ultrafiltration failure.

PMID- 9147565
TI  - 2nd European Peritoneal Dialysis Meeting. Gent, Belgium, March 11-12, 1996.
      Abstracts.

PMID- 9147566
TI  - [Prevalence of hepatitis C virus infection in adolescents].

PMID- 9147567
TI  - [Tobacco dependence in the diabetic population].

PMID- 9147568
TI  - [Since that is given...: a common problem in primary care].

PMID- 9147569
TI  - [Thoughts on drug prescription...].

PMID- 9147570
TI  - [Our international projection].

PMID- 9147571
TI  - [Bed-side doctor in the 21st century: virtual physician?].

PMID- 9147572
TI  - [Group techniques and relaxation in the treatment of several subtypes of anxiety:
      a non-randomized controlled trial].
AB  - OBJECTIVE: To evaluate the impact of group relaxation on women suffering distress
      and general anxiety disorders. DESIGN: A non-randomised study with a control.
      PARTICIPANTS: A sample of 32 women between 25 and 55 in each group (intervention
      and control) was used. They belonged to the El Naranjo Health District and fitted
      the diagnostic criteria. The intervention group underwent a course of group
      techniques and relaxation. Anxiety was evaluated using the STAI state
      characteristic test, before and after intervention, for both groups. A
      qualitative evaluation using discussion groups was also made. RESULTS: At the
      start of the study, the two groups were homogeneous regarding all the variables.
      The anxiety-state mean in the post-test for the study group was 22.96 +/- 13.3;
      and for the control group, 33.3 +/- 13.17, a statistically significant difference
      (p = 0.004). The post-test mean of the anxiety characteristic for the study group
      was 28.62 +/- 12.28; against 35.26 +/- 9.84 for the control group, which was also
      statistically significant (p = 0.02). CONCLUSIONS: This type of intervention is
      effective in reducing temporary anxiety and improves, to a small extent, an
      inbuilt tendency to react with anxiety. These groups provide a qualitative
      improvement in self-esteem and in the women's network of relationships.

PMID- 9147573
TI  - [Dietary habits and consumption patterns in a health district].
AB  - OBJECTIVE: To describe nutritional habits in a Health District by defining the
      patterns of food consumption. DESIGN: A descriptive, crossover study. SETTING:
      Health District of Molina de Segura, Murcia. METHOD: A community survey by
      interview of 1,071 people (95% confidence; accuracy to 3%), selected from the
      Municipal Roll by simple randomised sampling, was performed. The statistical
      methods were: Chi-squared and Student's tests, ANOVA, Pearson's linear
      correlation, factorial and discriminatory analysis. MEASUREMENTS AND MAIN
      RESULTS: 17.3%, especially men, never took milk products (p < 0.0005). 12.5%,
      mainly young people, consumed more than 3 eggs a week (p < 0.02). 85% ate fruit
      daily; 70%, green and root vegetables; and 78%, olive oil. 12.6% had pulses more
      than 3 days a week. Only 6.5% had potatoes or pasta daily. Among men and young
      people there was a "bar culture", along with a "fast food" pattern. CONCLUSIONS:
      The abandoned Mediterranean diet must be promoted. Measures should be taken to
      moderate young people's and men's alcohol consumption. "Fast food" and "bar
      culture" patterns are the most deeply rooted. The nutritional education of the
      chronically ill should also be emphasised.

PMID- 9147574
TI  - [A multicenter primary care study on alcohol consumption].
AB  - OBJECTIVES: To find records of alcoholic drink consumption in general medical
      records and actions taken when at-risk drinkers were identified. DESIGN: A
      descriptive study using clinical auditing at 4 Health Centres. PARTICIPANTS: 399
      Primary Care (PC) clinical records. MEASUREMENTS AND MAIN RESULTS: Only 24.8% of
      the clinical records included alcoholic drink consumption over the last two
      years. Only 11 (2.8%)-all for men-of the records examined fulfilled the criteria
      for the drinker being considered at-risk. Low recording of alcohol might be for
      different reasons: some related to the professionals, others to the internal
      organisation of the PC team, yet others due to the external support structure.
      Causes related to internal organisation and the professionals were considered
      priority, as it was harder to intervene from the team into external causes.
      CONCLUSIONS: The results show low recording of alcohol consumption and justify
      the design of specific interventions. The methodology of continual quality
      improvement helps us identify the causes, the possible solutions and to design
      the strategy for change.

PMID- 9147575
TI  - [Validity of the attendance pressure indicator in a primary care area].
AB  - OBJECTIVE: To measure the validity of the attendance pressure indicator in the
      Primary Care clinics at a Health Centre. DESIGN: An observational, crossover
      study. SETTING: Primary Care Area 3, Madrid. PATIENTS AND OTHER PARTICIPANTS:
      Stratified sampling by professional group and systematic sampling out of a total
      of 296 Primary Care team professionals in the area were performed. The size of
      the sample was 100: 40 general practitioners, 15 paediatricians and 45 nurses.
      Information on the attendance pressure indicator was gathered directly from the
      Health Centres and compared with that sent to Area 3's Information System (3-IS)
      by the professionals themselves. MEASUREMENTS AND MAIN RESULTS: The attendance
      pressure indicator showed the following ICC for Area 3: 0.86 (LL > or = 0.79) in
      general medicine, 0.79 (LL > or = 0.69) in paediatrics and 0.95 (LL > or = 0.93)
      in nursing. The over-notification found was: 1.35 users per day (p < 0.05) in
      general medicine, 1.47 (p < 0.05) in paediatrics and 0.47 in nursing.
      CONCLUSIONS: The measurement method of the attendance pressure indicator in
      Madrid's Primary Care Area 3 is valid for general medicine, paediatrics and
      nursing. A light, but statistically significant, over-notification to 3-IS was
      observed in general medicine and paediatrics, but this does not affect the
      validity of the indicator.

PMID- 9147576
TI  - [Carbon monoxide poisoning: a pending subject for physicians and users].
AB  - OBJECTIVE: To assess the incidence of cases of carbon monoxide poisoning
      diagnosed at a General Hospital's Casualty Department, to evaluate its clinical
      features and diagnostic difficulties, to find data on how much information the
      patients had on the risk of poisoning, what measures were adopted for a
      technician to check the apparatus which caused the poisoning, and on re-use.
      DESIGN: An observational descriptive study. SETTING: Casualty Department of a
      County Hospital with a catchment area of 80,000 people. PARTICIPANTS: Included in
      the survey were the 27 clinical histories for the cases of poisoning attended in
      Casualty at Igualada General Hospital in 1993. RESULTS: 27 poisoning cases were
      diagnosed (0.5/1,000 emergencies attended). Symptoms were non-specific in most
      cases, being mainly migraine, nausea/vomiting and feeling sick. CONCLUSIONS:
      Carbon monoxide poisoning is still an important cause of morbidity and mortality.
      Focus on the possible diagnosis during the winter months would enable new,
      potentially serious cases to be treated or avoided. Campaigns to warn the
      community and to check apparatuses causing poisoning are needed.

PMID- 9147577
TI  - [Effects of chronic diseases on the use of primary care by the aged].
AB  - OBJECTIVE: To analyse how often elderly people attend Primary Care (PC)
      consulting rooms and how attendance is affected by the number and kind of chronic
      pathologies those elderly people suffer. SETTING: A medical list from each of
      three Health Centres in the city of Granada was chosen. PATIENTS: All those over
      65 registered on these lists from 1990 to 1994 inclusive, 711 people in total,
      were included. The number of attendances and chronic illnesses were obtained from
      the Clinical Records. The outcome variable "Mean Annual Consultations" (MAC) over
      the study period was analysed by ANOVA and multiple linear regression. RESULTS:
      MAC was 5.79 (SD 4.20), with a range from 0 to 27 consultations. MACs were
      significantly higher among the elderly registered at the Doctors' Health Centre
      (p < 0.001), among women (p < 0.05) and for the presence of any of the
      pathologies under consideration (p < 0.01) except dementia. A relationship was
      found between the number of comorbidities and MAC (p < 0.001). In the scaled
      multiple regression analysis, the number of comorbidities, the first variable
      introduced into the model, explained 33% of variability in use. CONCLUSIONS: The
      number of chronic pathologies strongly determines elderly people's attendance at
      PC consulting rooms, independently of the kind of illness they suffer from.

PMID- 9147578
TI  - [Rational use of drugs for the aged].

PMID- 9147580
TI  - Tyrosine phosphorylation in peripheral lymphocytes from patients with systemic
      lupus erythematosus.
AB  - A comparative study of tyrosine phosphorylation was performed on peripheral blood
      lymphocytes from systemic lupus erythematosus (SLE) patients and from healthy
      donors. Freshly isolated SLE lymphocytes presented an elevated tyrosine
      phosphorylation level when compared to healthy donors lymphocytes (p = 0.005).
      Among all phosphorylated proteins, those called p120, p110, p80 and p55-p60 were
      more phosphorylated. The level of tyrosine phosphorylation of p120 and p110
      proteins discriminated significantly (p = 0.0048, respectively, p = 0.02) between
      SLE patients and healthy donors. Lymphocytes form SLE patients and healthy donors
      were then stimulated by cross-linking T cell antigens (CD3, CD4, CD8) to further
      distinguish the signal transduction between normal and pathologic lymphocytes. No
      statistical differences in the tyrosine phosphorylation pattern, following CD4 or
      CD8 cross-linking, were observed between SLE patients and healthy donors
      lymphocytes. CD3 cross-linking induced an effect on tyrosine phosphorylation
      different in SLE patients versus healthy donors lymphocytes. Thus, the
      lymphocytes of SLE patients were refractile in anti-CD3 stimulation in comparison
      with the healthy donors lymphocytes. Chi-square analysis demonstrated that a
      significantly larger number of healthy donors responded to anti-CD3 stimulation
      compared to SLE patients (p = 0.03). The high frequency of tyrosine
      phosphorylation of p110 and p80 proteins, following CD3 stimulation, in normal
      versus SLE lymphocytes, suggested that these proteins could be involved in
      abnormal signal transduction in SLE cells.

PMID- 9147579
TI  - Influence of adjuvants on the induction of autoantibodies to the thyrotropin
      receptor.
AB  - To determine the influence of adjuvant on the induction of antibodies to
      thyrotropin receptor (TSHR), we immunized BALB/c mice with a extracellular domain
      of the TSHR (ETSHR) protein in complete Freund's adjuvant (CFA), Titer Max (TM)
      and Gerbu. Similarly, control groups of mice were immunized with bovine serum
      albumin (BSA) in each of the different adjuvants. As determined by ELISA, ETSHR
      given along with CFA elicited high titers of antibodies to ETSHR which were
      mainly restricted to the IgG1 subclass. Mice immunized with ETSHR in TM also
      developed high titers of anti-ETSHR antibodies but had higher levels of both IgG1
      and IgG2a. However, immunization with ETSHR in Gerbu resulted in low titers of
      antibodies, restricted to IgG1 subclass. Immunization of mice with BSA in each of
      the three adjuvants induced higher antibody titers to BSA. The subclass of
      antibodies in mice immunized with BSA in CFA and TM were predominantly IgG1 and
      IgG2a with lower levels of IgG2b, whereas in Gerbu treated group, antibody to BSA
      was restricted to IgG1 subclass. Analysis of specificity of antibodies against
      ETSHR, in mice immunized with ETSHR, revealed that irrespective of the adjuvant
      used, the dominant reactivity was against peptide 1 (AA 22-41) with weaker
      reactivity against several other. peptides. The only exception was in mice
      immunized with ETSHR in TM which also showed significant reactivity against
      peptide 23 (AA 352-371). Mice immunized with the ETSHR in CFA or in TM showed
      elevated levels of serum TSH binding inhibitory immunoglobulins (TBII). However,
      mice immunized with ETSHR in Gerbu, which had lower titers of antibodies to
      ETSHR, showed normal TBII levels. These studies showed that adjuvant composition
      could influence the titer, subclass and fine specificity of antibodies to ETSHR
      which in turn could affect the development of TBII activity.

PMID- 9147581
TI  - Restricted heterogeneity and changing spectrotypes in autoantibodies to La/SS-B.
AB  - Isoelectric focusing (IEF) spectrotype of specific immunoglobulins has been
      studied as a marker for B-cell clonality. In the present study, the spectrotype
      of anti-La antibodies in human autoimmune sera were analyzed by newly developed
      IEF sandwich assay in which focused total immunoglobulin on filter papers are
      incubated with crude antigen followed by horse-radish peroxidase-labeled anti-La
      antibodies. The anti-La spectrotypes contained oligoclonal bands, the positions
      and patterns of which are different in each patient, suggesting the preferential
      expansion of limited numbers of anti-La producing B-cell clones unique to
      individual patients. Furthermore, the bands on anti-La spectrotype in
      sequentially obtained sera changed continuously, suggesting alteration in the
      expanding anti-La producing clones. These may reflect affinity maturation and/or
      diversification of the B-cell epitopes involving somatic mutation.

PMID- 9147582
TI  - Expression of CD45-restricted form B in (NZW x BXSB) F1 and MRL/Mp-lpr/lpr mice.
AB  - Expression of CD45RB on CD4+ or CD8+ cells in combination with TCRV beta usages
      (V beta 6, V beta 8.1, V beta 8.2, V beta 11 and V beta 17a) in normal mouse
      strains (BALD/c and C57BL/6) was compared with autoimmune-prone strains (NZW x
      BXSB) F1 and MRL/lpr) at young and old ages. The frequencies, and also the
      numbers of CD45RB- cells in CD4+ T cells with various TcR repertoires was
      significantly less in the autoimmune-prone stains at old ages, while, in normal
      control strains, they remained unchanged. Furthermore, CD4+/CD45RB- cells are
      CD44high and CD62L (L- selectin).low These findings suggest that most T cells,
      especially CD4+ T cells, in old W/BF1 and old MRL/lpr mice, were activated and
      this may reflect the elevation of autoantibodies and the progress of autoimmune
      status in aged autoimmune-prone mice. This will be discussed in relation to the
      progress of the autoimmune diseases.

PMID- 9147585
TI  - HLA typing of a family with systemic lupus erythematosus.

PMID- 9147583
TI  - T helper cell-dependent, microbial superantigen-mediated B cell activation in
      vivo.
AB  - We have utilized a severe combined immune-deficient (SCID) mouse adoptive
      transfer model to explore the in vivo immunostimulatory effects of bacterial
      superantigens (SAg). B cell reconstituted SCID recipients were treated with the
      Staphylococcus aureus-derived toxic shock syndrome toxin (TSST-1) alone or in
      conjunction with syngeneic L3T4+ TSST-1-reactive Th cells. Over several months of
      study, the repetitive administration of TSST-1 resulted in a prompt, transient
      increase in serum IgG levels. This response required both biologically active
      TSST-1 and Th cells. These findings demonstrate that certain bacterial SAgs can
      promote Th cell-dependent B cell activation and differentiation in vivo. These
      studies strengthen the analogy between SAg-mediated and allospecific Th-B cell
      interactions responsible for the autoimmune sequelae of graft-versus-host
      disease.

PMID- 9147584
TI  - The frequency of homozygous deletion of a developmentally regulated Vh gene
      (Humhv3005) is increased in patients with chronic idiopathic thrombocytopenic
      purpura.
AB  - Little is known of the genetic factors that may contribute to the development of
      chronic idiopathic thrombocytopenic purpura (cITP). We have previously shown that
      a developmentally regulated Vh gene (Humhv3005) is absent in 10/41 (24%) of
      patients with systemic lupus erythematosus while it is absent in only 7/88 (8%)
      of normal controls. This finding suggests that a homozygous deletion of an Ig
      variable (V) gene may alter the immune system and thus predispose the host to an
      autoimmune disorder. We have analyzed the same gene in 44 patients with cITP and
      found that Humhv3005 and like genes were absent in a higher percentage of
      patients (14 of 44, 31.8%) than they were absent in either normals (7/88, 8%, p =
      0.002) or thrombocytopenic patients without cITP (6/53, 11.3%, p = 0.042); the
      hv3005 deletion frequency in the latter group did not differ from that in normals
      (P = 0.74). These data suggest that deletions of Humhv3005 and/or highly
      homologous Vh genes may predispose individuals to the development of cITP, and
      may contribute toward production of pathogenic antiplatelet antibodies.

PMID- 9147586
TI  - The effect of incomplete knowledge of parameter values on single- and multiple
      stage designs for logistic regression.
AB  - We consider the design of single- and multiple-stage dose-response trials in
      which the probability of response is a logistic function of the dose. Knowledge
      of the parameters of the logistic at the time of planning the trial is
      represented by a Gaussian prior distribution. Methods are presented for
      determining a design that approximately optimizes a measure of the accuracy of
      estimation averaged over the prior distribution. Changes in design due to
      uncertainty of parameter values are described as well as the changes in sample
      size required to produce a specified precision. In multiple-stage trials, the
      initial stage is planned as if it were the only stage. For succeeding stages, the
      initial Gaussian prior distribution is updated using outcomes at the previous
      stages. At each such stage, the design optimizes a chosen criterion averaged over
      the updated prior distribution. The effectiveness of this methodology is
      evaluated by comparing the operating characteristics of two-stage designs with
      those of single-stage designs.

PMID- 9147587
TI  - The behavior of the P-value when the alternative hypothesis is true.
AB  - The P-value is a random variable derived from the distribution of the test
      statistic used to analyze a data set and to test a null hypothesis. Under the
      null hypothesis, the P-value based on a continuous test statistic has a uniform
      distribution over the interval [0, 1], regardless of the sample size of the
      experiment. In contrast, the distribution of the P-value under the alternative
      hypothesis is a function of both sample size and the true value or range of true
      values of the tested parameter. The characteristics, such as mean and
      percentiles, of the P-value distribution can give valuable insight into how the P
      value behaves for a variety of parameter values and sample sizes. Potential
      applications of the P-value distribution under the alternative hypothesis to the
      design, analysis, and interpretation of results of clinical trials are
      considered.

PMID- 9147588
TI  - Regression models for mixed discrete and continuous responses with potentially
      missing values.
AB  - In this paper a likelihood-based method for analyzing mixed discrete and
      continuous regression models is proposed. We focus on marginal regression models,
      that is, models in which the marginal expectation of the response vector is
      related to covariates by known link functions. The proposed model is based on an
      extension of the general location model of Olkin and Tate (1961, Annals of
      Mathematical Statistics 32, 448-465), and can accommodate missing responses. When
      there are no missing data, our particular choice of parameterization yields
      maximum likelihood estimates of the marginal mean parameters that are robust to
      misspecification of the association between the responses. This robustness
      property does not, in general, hold for the case of incomplete data. There are a
      number of potential benefits of a multivariate approach over separate analyses of
      the distinct responses. First, a multivariate analysis can exploit the
      correlation structure of the response vector to address intrinsically
      multivariate questions. Second, multivariate test statistics allow for control
      over the inflation of the type I error that results when separate analyses of the
      distinct responses are performed without accounting for multiple comparisons.
      Third, it is generally possible to obtain more precise parameter estimates by
      accounting for the association between the responses. Finally, separate analyses
      of the distinct responses may be difficult to interpret when there is nonresponse
      because different sets of individuals contribute to each analysis. Furthermore,
      separate analyses can introduce bias when the missing responses are missing at
      random (MAR). A multivariate analysis can circumvent both of these problems. The
      proposed methods are applied to two biomedical datasets.

PMID- 9147589
TI  - Regression calibration in failure time regression.
AB  - In this paper we study a regression calibration method for failure time
      regression analysis when data on some covariates are missing or mismeasured. The
      method estimates the missing data based on the data structure estimated from a
      validation data set, a random subsample of the study cohort in which covariates
      are always observed. Ordinary Cox (1972; Journal of the Royal Statistical
      Society, Series B 34, 187-220) regression is then applied to estimate the
      regression coefficients, using the observed covariates in the validation data set
      and the estimated covariates in the nonvalidation data set. The method can be
      easily implemented. We present the asymptotic theory of the proposed estimator.
      Finite sample performance is examined and compared with an estimated partial
      likelihood estimator and other related methods via simulation studies, where the
      proposed method performs well even though it is technically inconsistent.
      Finally, we illustrate the method with a mouse leukemia data set.

PMID- 9147590
TI  - Modeling of time trends and interactions in vital rates using restricted
      regression splines.
AB  - For the analysis of time trends in incidence and mortality rates, the age-period
      cohort (apc) model has became a widely accepted method. The considered data are
      arranged in a two-way table by age group and calendar period, which are mostly
      subdivided into 5- or 10-year intervals. The disadvantage of this approach is the
      loss of information by data aggregation and the problems of estimating
      interactions in the two-way layout without replications. In this article we show
      how splines can be useful when yearly data, i.e., 1-year age groups and 1-year
      periods, are given. The estimated spline curves are still smooth and represent
      yearly changes in the time trends. Further, it is straightforward to include
      interaction terms by the tensor product of the spline functions. If the data are
      given in a nonrectangular table, e.g., 5-year age groups and 1-year periods, the
      period and cohort variables can be parameterized by splines, while the age
      variable is parameterized as fixed effect levels, which leads to a semiparametric
      apc model. An important methodological issue in developing the nonparametric and
      semiparametric models is stability of the estimated spline curve at the
      boundaries. Here cubic regression splines will be used, which are constrained to
      be linear in the tails. Another point of importance is the nonidentifiability
      problem due to the linear dependency of the three time variables. This will be
      handled by decomposing the basis of each spline by orthogonal projection into
      constant, linear, and nonlinear terms, as suggested by Holford (1983, Biometrics
      39, 311-324) for the traditional apc model. The advantage of using splines for
      yearly data compared to the traditional approach for aggregated data is the more
      accurate curve estimation for the nonlinear trend changes and the simple way of
      modeling interactions between the time variables. The method will be demonstrated
      with hypothetical data as well as with cancer mortality data.

PMID- 9147591
TI  - Estimating lead time and sensitivity in a screening program without estimating
      the incidence in the screened group.
AB  - Early indicators of the effectiveness of a screening test for chronic diseases
      such as breast cancer are the length of time the diagnosis is advanced by
      screening, the lead time, and the sensitivity of the screening test. This paper
      describes a model for simultaneously estimating the mean lead time and the
      sensitivity when only the number of cancers detected at the successive screenings
      and the number of cancers occurring in the time interval between the screening
      examinations are known. This model is particularly useful in assessing the effect
      of screening when the underlying cancer incidence in the screened group is
      unknown. The model is fitted to the data of 235 screen-detected breast cancer
      cases and 146 interval cancers diagnosed across 6 screening rounds of the program
      in Nijmegen. The maximum likelihood estimate for the mean lead time ranges from
      1.3 years in the under age 50 group to 2.2 years in the age 50-65 group, both
      estimates having large confidence intervals. The corresponding sensitivity
      estimates are 0.92 and 1.00.

PMID- 9147592
TI  - Inference for phylogenies under a hybrid parsimony method: evolutionary-symmetric
      transversion parsimony.
AB  - A new method is proposed for inferring topology for evolutionary trees. Existing
      methods have complementary strengths and weaknesses. Maximum and transversion
      parsimony are powerful methods, but they lack statistical consistency, that is,
      they do not always infer the correct tree as the sequence length becomes very
      large. Evolutionary parsimony overcomes this deficiency, but it may lack
      sufficient power when sequence length is small (less than 1000 aligned
      nucleotides; Sinsheimer, Lake, and Little, 1996, Biometrics 52, 193-210). Our
      proposed method, evolutionary-symmetric transversion parsimony, is a hybrid that
      retains the consistency of evolutionary parsimony, while increasing power by
      incorporating a modified form of transversion parsimony within a statistical
      model. The method requires choice of a parameter gamma that represents the prior
      probability that symmetric transversion parsimony yields consistent results.
      Properties of the method are assessed for a variety of choices of gamma in a
      large simulation study. In general, inference under the evolutionary-symmetric
      transversion parsimony has more discriminating power than inference under
      evolutionary parsimony and is better calibrated than inference under symmetric
      transversion parsimony. The results are quite robust to the choice of gamma,
      indicating a value of 0.90 as a reasonable overall choice when the true value of
      gamma ranges between 0.85 to 1.00. Our method is, like evolutionary parsimony and
      maximum parsimony, computationally straightforward. The same statistical approach
      can be applied to combine evolutionary parsimony with other inconsistent methods,
      such as maximum parsimony, but at the expense of more difficult computations.

PMID- 9147593
TI  - Large hierarchical Bayesian analysis of multivariate survival data.
AB  - Failure times that are grouped according to shared environments arise commonly in
      statistical practice. That is, multiple responses may be observed for each of
      many units. For instance, the units might be patients or centers in a clinical
      trial setting. Bayesian hierarchical models are appropriate for data analysis in
      this context. At the first stage of the model, survival times can be modelled via
      the Cox partial likelihood, using a justification due to Kalbfleisch (1978,
      Journal of the Royal Statistical Society, Series B 40, 214-221). Thus,
      questionable parametric assumptions are avoided. Conventional wisdom dictates
      that it is comparatively safe to make parametric assumptions at subsequent
      stages. Thus, unit-specific parameters are modelled parametrically. The posterior
      distribution of parameters given observed data is examined using Markov chain
      Monte Carlo methods. Specifically, the hybrid Monte Carlo method, as described by
      Neal (1993a, in Advances in Neural Information Processing 5, 475-482; 1993b,
      Probabilistic inference using Markov chain Monte Carlo methods), is utilized.

PMID- 9147594
TI  - Modeling schizophrenic behavior using general mixture components.
AB  - This article proposes a novel and general mixture component model, the features
      of which include a hierarchical structure with random effects, mixture components
      characterized by ANOVA-like linear regressions, and mixing mechanisms governed by
      logistic regressions. The model was developed as a consequence of attending to
      long-standing psychological theory about schizophrenic behavior. Scientifically
      revealing results are obtained by fitting the model to a data set concerning
      nonschizophrenic and schizophrenic eye-tracking behavior under different
      conditions. Included are descriptions of the algorithms for model fitting,
      specifically the ECM/SECM algorithms for large sample modal inference, and the
      Gibbs sampler for simulating the posterior distribution. For guidance on model
      comparison and selection, we use posterior predictive check distributions to
      obtain posterior predictive p-values for likelihood ratio statistics, which do
      not have asymptotic chi 2 reference distributions. These posterior predictive p
      values suggest that all the mixture components in our model are necessary. The
      final model is selected using a combination of scientific parsimony, the
      posterior predictive p-values, and the posterior distributions of relevant
      parameters.

PMID- 9147595
TI  - Transformations to additivity in measurement error models.
AB  - In many problems, one wants to model the relationship between a response Y and a
      covariate X. Sometimes it is difficult, expensive, or even impossible to observe
      X directly, but one can instead observe a substitute variable W that is easier to
      obtain. By far, the most common model for the relationship between the actual
      covariate of interest X and the substitute W is W = X + U, where the variable U
      represents measurement error. This assumption of additive measurement error may
      be unreasonable for certain data sets. We propose a new model, namely h(W) = h(X)
      + U, where h(.) is a monotone transformation function selected from some family H
      of monotone functions. The idea of the new model is that, in the correct scale,
      measurement error is additive. We propose two possible transformation families H.
      One is based on selecting a transformation that makes the within-sample mean and
      standard deviation of replicated W's uncorrelated. The second is based on
      selecting the transformation so that the errors (U's) fit a prespecified
      distribution. Transformation families used are the parametric power
      transformations and a cubic spline family. Several data examples are presented to
      illustrate the methods.

PMID- 9147596
TI  - Semiparametric estimation of major gene and family-specific random effects for
      age of onset.
AB  - Analysis of familial diseases with variable age of onset is a common problem in
      human genetics. Most existing methods make some parametric distributional
      assumption on age of onset, and few methods have been designed with the goal of
      testing the hypothesis of a Mendelian gene against other hypotheses of familial
      dependence. We introduce the Cox model with major genetic and random familial
      effects to model age-of-onset dependence patterns among family members and to
      incorporate family heterogeneity. This model allows testing for and estimating
      major gene effects in the presence of residual correlations. Generalized maximum
      likelihood estimation using a Monte Carlo EM algorithm is used for parameter
      estimation. The methods are illustrated by a simulated data set and a data set
      from a case-control family study of breast cancer.

PMID- 9147597
TI  - A discrete survival model with random effects: an application to time to
      pregnancy.
AB  - Time to pregnancy, the number of menstrual cycles it takes a couple to conceive,
      and various covariates have been collected among couples ultimately achieving
      conception. To assess the influence of the covariates, we constructed a discrete
      survival model that allows time-dependent covariates. A random effect was
      included to account for unobserved heterogeneity. The collected waiting times are
      obtained through retrospective ascertainment and are analyzed as truncated data.
      Maximum likelihood estimation was implemented by Fisher scoring through
      iteratively reweighted least squares.

PMID- 9147598
TI  - A joint model for survival and longitudinal data measured with error.
AB  - The relationship between a longitudinal covariate and a failure time process can
      be assessed using the Cox proportional hazards regression model. We consider the
      problem of estimating the parameters in the Cox model when the longitudinal
      covariate is measured infrequently and with measurement error. We assume a
      repeated measures random effects model for the covariate process. Estimates of
      the parameters are obtained by maximizing the joint likelihood for the covariate
      process and the failure time process. This approach uses the available
      information optimally because we use both the covariate and survival data
      simultaneously. Parameters are estimated using the expectation-maximization
      algorithm. We argue that such a method is superior to naive methods where one
      maximizes the partial likelihood of the Cox model using the observed covariate
      values. It also improves on two-stage methods where, in the first stage,
      empirical Bayes estimates of the covariate process are computed and then used as
      time-dependent covariates in a second stage to find the parameters in the Cox
      model that maximize the partial likelihood.

PMID- 9147599
TI  - A logistic model for trend in 2 x 2 x kappa tables with applications to meta
      analyses.
AB  - There recently has been an increased interest in examining the relationship
      between the baseline (control) risk of an adverse outcome and the magnitude of
      the treatment effect (Brand and Kragt, 1992, Statistics in Medicine 11, 2077
      2082; Davey Smith, Song, and Sheldon, 1993, The British Medical Journal 306, 1367
      1373; Senn, 1994, Statistics in Medicine 13, 293-294). To facilitate such an
      examination, we propose a logistic model in which the relationship between the
      treatment effect, as measured by the log odds ratio, and the baseline risk is
      specified parametrically. This procedure is founded on a product-binomial
      likelihood and generates maximum likelihood estimates of the baseline event rates
      and two parameters characterizing the trend in the treatment effect. We fit this
      model to data from a meta-analysis involving the treatment of women at risk of
      preterm labor and contrast our findings with those of an earlier analysis.

PMID- 9147600
TI  - A logistic-bivariate normal model for overdispersed two-state Markov processes.
AB  - We describe a logistic-bivariate normal mixture model for a two-state Markov
      chain in which each individual makes transitions between states according to a
      subject-specific transition probability matrix. The use of the bivariate normal
      mixing distribution facilitates inferences regarding the correlation of the
      random effects and hence provides insight as to the nature of the subject-to
      subject variability in the transition probabilities. Tests regarding the
      correlation can be based on likelihood ratio, score, or Wald statistics.
      Estimates of the transition intensities of a latent continuous time conditionally
      Markov process may also be computed. We illustrate this methodology by
      application to a parasitic infection field study and contrast our findings with
      those previously published on this data set.

PMID- 9147601
TI  - A computationally simpler algorithm for the UMVUE of a normal mean following a
      group sequential trial.
AB  - When using data collected in a group sequential clinical trial, the sample mean
      is no longer the uniform minimum variance unbiased estimator (UMVUE) of the mean
      of a normal distribution. Emerson (1993, Computers and Biomedical Research, 26,
      68-73) described an algorithm for computing the UMVUE in this setting. This
      algorithm, although computationally expensive, used only the basic software
      necessary for deriving group sequential boundaries. In this paper, we present an
      improved algorithm that results in greatly decreased computation times.

PMID- 9147602
TI  - Analysis of correlated ROC areas in diagnostic testing.
AB  - This paper focuses on methods of analysis of areas under receiver operating
      characteristic (ROC) curves. Analysis of ROC areas should incorporate the
      correlation structure of repeated measurements taken on the same set of cases and
      the paucity of measurements per treatment resulting from an effective
      summarization of cases into a few area measures of diagnostic accuracy. The
      repeated nature of ROC data has been taken into consideration in the analysis
      methods previously suggested by Swets and Pickett (1982, Evaluation of Diagnostic
      Systems: Methods from Signal Detection Theory), Hanley and McNeil (1983,
      Radiology 148, 839-843), and DeLong, DeLong, and Clarke-Pearson (1988, Biometrics
      44, 837-845). DeLong et al.'s procedure is extended to a Wald test for general
      situations of diagnostic testing. The method of analyzing jackknife pseudovalues
      by treating them as data is extremely useful when the number of area measures to
      be tested is quite small. The Wald test based on covariances of multivariate
      multisample U-statistics is compared with two approaches of analyzing
      pseudovalues, the univariate mixed-model analysis of variance (ANOVA) for
      repeated measurements and the three-way factorial ANOVA. Monte Carlo simulations
      demonstrate that the three tests give good approximation to the nominal size at
      the 5% levels for large sample sizes, but the paired t-test using ROC areas as
      data lacks the power of the other three tests and Hanley and McNeil's method is
      inappropriate for testing diagnostic accuracies. The Wald statistic performs
      better than the ANOVAs of pseudovalues. Jackknifing schemes of multiple deletion
      where different structures of normal and diseased distributions are accounted for
      appear to perform slightly better than simple multiple-deletion schemes but no
      appreciable power difference is apparent, and deletion of too many cases at a
      time may sacrifice power. These methods have important applications in diagnostic
      testing in ROC studies of radiology and of medicine in general.

PMID- 9147603
TI  - Testing for treatment effect in the presence of regression toward the mean.
AB  - We are often faced with the statistical problem of evaluating the effect of a
      treatment in the extreme of a population. This requires taking measurements on
      truncated random variables and, hence, it becomes necessary to take proper
      account of the effect of regression toward the mean. The usual statistical
      procedures are inappropriate for testing treatment effect in the presence of
      regression toward the mean. Likelihood ratio and score tests based on truncated
      distributions should provide valid statistical inferences in these situations. We
      conducted simulation studies to investigate the properties of these methods and
      found that the likelihood ratio test performs well even when the sample size is
      moderate, whereas the score test does not seem to control the nominal
      significance level. We compared the likelihood ratio test to a regression-based t
      test, assuming the mean of the baseline distribution to be known, and found the
      likelihood ratio test more powerful. In the case where the baseline mean is
      unknown, we also investigated Wald's test and compared it with the likelihood
      ratio test and score test with respect to validity and power using simulation.
      Wald's test and the score test do not control the nominal significance level
      unless the sample size is extremely large. Overall, the likelihood ratio test has
      the best performance among all the methods studied. The proposed likelihood ratio
      test is illustrated using an example of a cholesterol study.

PMID- 9147604
TI  - Comparing two diagnostic tests against the same "gold standard" in the same
      sample.
AB  - Methods are proposed for comparing two diagnostic tests for the same data where a
      threshold for positive for each test is specified. One method contrasts the
      diagnostic tests' estimated risks. A second method compares the two tests' kappa
      coefficients. When thresholds for positive test results are specified a priori,
      maximum likelihood estimators and their asymptotic variances are derived and test
      statistics are presented for both case-control and naturalistic methods of
      sampling. The bootstrap is proposed as a method to assess differences in risk
      estimators when thresholds for positive test results are chosen by scanning the
      data. Examples are given to illustrate the methods.

PMID- 9147605
TI  - Tests to detect clustering of infected individuals within families.
AB  - A new simple test to detect within-family clustering of infected individuals is
      proposed. The test is derived as the score test for several different parametric
      models designed to allow an increased within-family infectivity. The new test is
      compared with other tests proposed to detect the same type of clustering caused
      by increased within-family infectivity. Applications of household disease data
      and simulations are used to illustrate the theory.

PMID- 9147606
TI  - The role of multidrug resistance-associated protein (MRP) expression in multidrug
      resistance.
AB  - Multidrug resistance (MDR) is a major hindrance to the successful treatment of
      neoplastic disease. The development of resistance to multiple chemotherapeutic
      drugs is a complex phenomenon which has been described in both tumor cell lines
      and human cancers. To date, two mechanisms associated with overexpression of
      membrane glycoproteins that function as energy-dependent efflux pumps to reduce
      intracellular drug levels have been identified for MDR. The first described was
      the product of the MDR1 gene, P-glycoprotein. The second mechanism is mediated by
      overexpression of the multidrug resistance-associated protein (MRP). While these
      proteins both belong to the ATP-binding cassette superfamily of transporters,
      they are only distantly related. Despite this low homology, they mediate
      resistance to a similar range of chemotherapeutic drugs. While P-glycoprotein has
      been well described in the literature, much less is known about the recently
      identified MRP. This review gives an overview of the characteristics of MRP at
      both the phenotypic and genotypic levels, and discusses its possible relevance in
      drug-refractory cancer.

PMID- 9147607
TI  - Protein kinase C: a worthwhile target for anticancer drugs?
AB  - Protein kinase C (PKC) is an enzyme family with serine/threonine kinase function
      which is involved in the transduction of signals for cell proliferation and
      differentiation. The important role played in processes relevant to neoplastic
      transformation, carcinogenesis and tumor cell invasion renders PKC a potentially
      suitable target for anticancer therapy. Bryostatin 1, a macrocyclic lactone
      isolated from Bugula nerutina, is a partial PKC agonist, and has shown potent
      antineoplastic properties in vitro and in vivo. Staurosporine, an alkaloid
      isolated from microbial sources, is ine of the most potent PKC inhibitors and has
      shown high antiproliferative activity in vitro, but poor selectivity.
      Staurosporine analogs have thus been synthesize with the aim of obtaining more
      selective PKC inhibition; among these, CGP 41251 has shown reduced PKC inhibitory
      activity, but a higher degree of selectivity when assayed for inhibition of
      different kinases. Several studies indicate a role for PKC in the regulation of
      the multidrug resistance (MDR) phenotype, since several PKC inhibitors are able
      to partially reverse MDR and inhibit P-glycoprotein (Pgp) phosphorylation. The
      MDR phenotype is also associated with variation in PKC isoenzyme content, in
      particular with PKC-alpha overexpression. While adequate PKC modulation might
      offer an attractive concept to modulate MDR, other potential mechanisms of PKC
      interaction with anticancer drugs exist and have been documented, such as the
      enhancement of chemotherapy-induced apoptosis by safingol, a specific PKC
      inhibitor. Three phase I clinical trials with bryostatin have been completed so
      far and have shown that myalgia is the dose-limiting toxicity, while some
      antitumor activity is evident. Safingol is presently undergoing a phase I
      clinical trial in combination with doxorubicin. While no definitive data are
      presently available, it appears that safingol plasma levels approach those
      associated with chemopotentiation in animals and no pharmacokinetic interaction
      between the two drugs exists. Drugs targeting PKC are well work considering for
      clinical trials, particularly for their potential as modulators of currently
      available cytotoxic agents.

PMID- 9147608
TI  - Folate-based thymidylate synthase inhibitors in cancer chemotherapy.
AB  - Understanding the relationship between chemical structure and biological
      properties of folate analogs, particularly their interactions with the target
      enzymes, transport proteins and folate-metabolizing enzyme, folylpolyglutamate
      synthetase (FPGS), has enabled the rational design and development of the
      selective thymidylate synthase (TS) inhibitors with folate-based structures for
      clinical uses. These compounds specifically inhibit TS devoid of concomitant
      effects at other loci, unlike 5-fluorouracil (5-FU). ZD1694 ('Tomudex') was
      designed as a non-nephrotoxic and highly active analog of N10-propargyl-5,8
      dideazafolic acid (CB3717), which is a potent TS inhibitor but had unacceptable
      nephrotoxicity caused by its poor water solubility. The potent cytotoxic activity
      of ZD1694 is dependent upon active uptake into cells via the reduced folate
      carrier (RFC), and subsequent rapid and extensive metabolism to polyglutamate
      forms inside cells. Marked enhancement of the TS inhibitory activity has been
      noted as the glutamate chain is elongated. Polyglutamation is critical to the
      biological activity of ZD1694 against tumor and normal proliferating tissues. The
      retentive property of ZD1694 polyglutamates inside cells led to a single,
      infrequent administration schedule in clinical studies. ZD1694 has completed
      phase I and phase II evaluation with activity observed in several tumor types,
      particularly in colorectal cancer with a 26% objective response rate. A recent
      European phase III study of ZD1694, randomized against a 5-FU plus leucovorin
      regimen, demonstrated an equivalent response rate for advanced colorectal cancer
      (complete or partial responses; 20 versus 17%) and less toxicity than seen with
      the latter regimen. The newer selective TS inhibitors, which retain potency for
      TS inhibition but are not substrates for RFC and/or FPGS, are currently under
      clinical evaluation. These classes of compound may have benefits for
      circumvention of resistance by virtue of alterations in these protein functions
      and for the management of toxicity.

PMID- 9147609
TI  - Effects of WR-2721 (amifostine) and its metabolite WR-1065 on the
      antiproliferative activity of chemotherapeutic agents on neuroblastoma cells in
      vitro.
AB  - Amifostine (WR-2721) is currently being investigated as a potential protector of
      normal tissues during chemotherapy in adult and pediatric cancer patients. The
      marked reduction of bone marrow and renal toxicity by amifostine is well
      documented, but data are lacking whether the anticancer activity of cytostatic
      drugs is also preserved in neuroblastoma as the second most common pediatric
      malignancy. We investigated the cytotoxic effect of six drugs on two
      neuroblastoma cells lines chosen for their presence or absence of N-myc
      amplification and PGY1 overexpression: IMR-5 (N-myc 25 x, PGY1-negative), CHP-100
      (N-myc 1x, PGY1-positive) in vitro in the presence and absence of WR-2721 and its
      active metabolite WR-1065 using the monolayer proliferation assay. Doxorubicin,
      vincristine, etoposide, cisplatin, 4-hydroperoxycyclophosphamide and 4
      hydroperoxyifosfamide were equally cytotoxic with and without preincubation of WR
      2721 (14 mM) or WR-1065 (40 microM) as shown by virtually identical dose-response
      curves and ID50 values. We conclude that WR-2721 and WR-1065 did not reduce the
      cytostatic activity of six commonly used drugs on neuroblastoma cell lines in
      vitro.

PMID- 9147610
TI  - Plasma pharmacokinetics of idarubicin and its 13-dihydro metabolite--a comparison
      of bolus versus 2 h infusion during a 3 day course.
AB  - The plasma pharmacokinetics of a second generation anthracycline derivative,
      idarubicin (Ida), have been studied in 17 patients with acute myelocytic leukemia
      (AML) and high risk features. The drug (10 mg/m2) was given in a randomized cross
      over design as 3 min and 2 h infusions for three consecutive days. Cytosine
      arabinoside (Ara-C, 1 g/m2) was given on days 1-4. The plasma concentration time
      course of Ida was most properly described by the three-compartment
      pharmacokinetic model, independent of administration time. The maximum plasma
      concentration (Cmax) of Ida was reduced by a factor of 3 by increasing the
      infusion time from 3 min to 2 h. The pharmacokinetic pattern of the active
      metabolite idarubicinol (IdaOH) was only to a minor extent affected by the longer
      infusion time. The time course of IdaOH following each dose of Ida was accurately
      described by the one-compartment model with a first-order formation phase. The
      are under the plasma concentration versus time curves (AUC) of Ida and IdaOH were
      not affected by the administration time. Following Ida in combination with Ara-C,
      the medial duration of leukopenia (< 1.0 x 10(9)/l) was 14 days (range 5-56) and
      of thrombocytopenia (< 50 x 10(9)/l) was 22 days (range 7-120). The large
      majority of patients developed infectious complications. Two patients with MDS
      AML showed a good response. The results of the present study give no evidence of
      reduced hematologic toxicity by increasing the administration time of Ida from 3
      min to 2 h. However, minimizing Cmax, by administration of Ida as prolonged
      infusion during a 3 day course, might be clinically important in order to reduce
      cardiotoxicity and hopefully to increase anti-tumor efficacy through an increased
      accumulation of Ida and IdaOH in leukemic cells.

PMID- 9147611
TI  - Evaluation of Taxol in head and neck squamous carcinoma multicellular tumor
      spheroids.
AB  - Taxol cytotoxicity was evaluated in human head and neck squamous carcinoma cell
      lines growing as multicellular tumor spheroids (MTS) and compared with
      monolayered culture using conventional clonogenic assays. End points were
      respectively the concentration inhibiting 50% of the cellular growth (IC50) in
      clonogenic assays and the concentration required to induce a 50% decrease in the
      MTS volume (ID50) or number in the overall spheroid population (SCC50). A
      significant difference was observed when the cells were exposed for 10 days to
      Taxol as a consequence of the different growth kinetics of the spheroids. After
      16 day exposure of spheroids to Taxol, no difference remained between ID50 and
      IC50. In addition, a significant correlation was found between individual
      spheroid sensitivity to Taxol (ID50) and the spheroid population sensitivity
      (SCC50). Both parameters (ID50 and SCC50) defined in cell models appear useful
      for the evaluation of chemosensitivity of three-dimensional structures known to
      be closer to in vivo tumor models.

PMID- 9147612
TI  - Activation of the retinoic acid receptor beta gene by 5-aza-2'-deoxycytidine in
      human DLD-1 colon carcinoma cells.
AB  - We previously reported that 5-aza-2'-deoxycytidine (5-Aza-CdR) in combination
      with all-trans retinoic acid (ATRA) produced a synergistic antineoplastic effect
      on DLD-1 colon carcinoma cells. We also observed that 5-Aza-CdR, a potent
      inhibitor of DNA methylation, increased the expression of retinoic acid receptor
      (RAR)-beta. Methylation of cytosine in the promoter-first exon region of genes
      has been reported to silence their expression. In an attempt to clarify the
      mechanism responsible for the activation of the RAR-beta gene by 5-Aza-CdR in DLD
      1 colon carcinoma cells, we investigated its methylation state by Southern
      blotting. Our results indicate that DNA hypermethylation of the RAR-beta gene, a
      putative tumor suppressor gene, may be the mechanism of silencing its expression
      in these tumor cells. We also reported that a different schedule of 5-Aza-CdR and
      ATRA produced a synergistic antineoplastic effect on the colon carcinoma cells.

PMID- 9147613
TI  - Inhibition of the growth of 12V-ras-transformed rat fibroblasts by
      acetylsalicylic acid correlates with inhibition of NF-kappa B.
AB  - Epidemiological studies have demonstrated a correlation between regular aspirin
      (acetylsalicylic acid; ASA) use and a decreased risk for the development of
      cancer. We here show that ASA inhibits the growth of 12V-ras-transformed rat
      fibroblasts in vitro at pharmacological concentrations. This effect appeared to
      be unrelated to inhibition of cyclooxygenase, since other cyclooxygenase
      inhibitors did not inhibit cell growth. A number of nuclear transcription factors
      have been implicated as mediators of transformation. ASA has recently been
      reported to inhibit the activation of one such factor, NF-kappa B. We found that
      NF-kappa B binding activity was decreased in ASA-treated 12V-ras-transformed
      cells. Inhibition of NF-kappa B activation was not due to a general inhibitory
      effect, since AP-1 binding activity was not affected. We conclude that ASA
      inhibits the growth of 12V-ras-transformed fibroblasts, possibly via inhibition
      of NF-kappa B.

PMID- 9147614
TI  - Determination of the maximal tumor/normal skin ratio after HpD or m-THPC
      administration in hairless mouse (SKh-1) by fluorescence spectroscopy--a non
      invasive method.
AB  - Two major steps in our study on the treatment of skin tumors by photochemotherapy
      (PCT) were the development of a skin tumor model in hairless mice by chemical
      carcinogenesis and by the use fluorescence spectroscopy, a semi-quantitative and
      non-invasive method, to determine the time after i.p. injection of
      photosensitizer when the tumor/normal skin ratio is the highest. Carcinogenesis
      provided mice bearing many benign papillomas and these were used to determine the
      tumor/normal skin ratios of two photosensitizers by fluorescence spectroscopy.
      Hematoporphyrin derivative (HpD) (5 mg/kg body weight) and m-tetra(hydroxyphenyl)
      chlorin (m-THPC) (0.3 mg/kg body weight) were injected, and fluorescence measured
      at 4, 8, 24, 48, 72 and 96 h after injection. The tumor/normal skin ratio was 6.2
      for HpD and 5.1 for m-THPC. The times required to reach these ratios were 48 h
      for HpD and 72 h for m-THPC. Published reports indicate that m-THPC gives a much
      higher tumor/normal skin ratio than HpD. These results must be confirmed by
      organic extraction. Photodynamic therapy with the same doses of HpD and m-THPC
      used in this pharmacokinetic study must also be carried out to compare the
      toxicities of the two photosensitizers and to determine which is best for this
      type of tumor.

PMID- 9147615
TI  - m-N-N-bis(2-chloroethyl)aminocinnamic acid and four new homo-aza-steroidal esters
      induce chromosomal abnormalities and affect protein synthesis in human
      lymphocytes in vitro.
AB  - The alkylating agent m-N,N-bis(2-chloroethyl)aminocinnamic acid (m-ACA) and four
      new homo-aza-steroidal esters were studied for their ability to induce
      chromosomal abnormalities and to affect protein synthesis in human lymphocytes in
      vitro. A mitotic index reduction and an increase in the total number of
      aberrations were observed. Analysis of chromosomal abnormalities has shown that
      these are mainly chromatid breaks. A decrease in protein synthesis was also
      observed that seems to fit with the order of activity of the above compounds
      reflected in the induction of chromosomal aberrations. The observation that
      protein synthesis and the induction of chromosomal aberrations are affected by
      these chemicals may reflect interactions between these molecules and DNA that
      result in structural chromosome changes and decreased protein synthesis.

PMID- 9147616
TI  - Potentiation of antitumor efficacy of paclitaxel by recombinant tumor necrosis
      factor-alpha.
AB  - We studied the combination of tumor necrosis factor (TNF) and paclitaxel. Our aim
      was to determine whether TNF increases the antitumor efficacy of paclitaxel and
      if so whether the increase is mediated through the enhancement of apoptosis
      induction by paclitaxel. Mice bearing 6 mm MCa-K or MCa-4 mammary carcinomas, OCa
      I ovarian carcinomas, or HCa-I hepatocarcinomas in their legs were treated with
      TNF, paclitaxel of their combination. TNF was administered i.p. daily at a dose
      of 10 micrograms per mouse for 7 days; paclitaxel at a dose of 40 mg/kg per mouse
      was given as a single i.v. injection 1 h before the second dose of TNF. Tumor
      growth delay was used as the endpoint of tumor response to the treatments. The
      results showed that the combination was either additive or supraadditive;
      supraadditive action occurred in three of the four tumors tested. The enhancement
      factors (EFs) were 1.24 for MCa-K, 1.53 for MCa-4, 1.0 for OCa-I and 2.17 for HCa
      I. Histological analysis of treated MCa-K tumors revealed that TNF alone did not
      induce apoptosis of tumor cells, but in the combination it enhanced the apoptotic
      response to paclitaxel. Thus, TNF increased the antitumor efficacy of paclitaxel
      by enhancing cellular sensitivity to paclitaxel's induction of apoptosis. The
      results imply that the combination of TNF and paclitaxel has potential as a
      treatment for cancer.

PMID- 9147617
TI  - Synthesis and in vivo antitumor activity of new heterocyclic derivatives of the
      1,3,4-thiadiazolium-2-aminide class.
AB  - Four new mesoionic compounds derivates of 4-phenyl-5-(4-X-cinnamoyl)-1,3,4
      thiadiazolium-2-phenylamine chlorides were synthesized and their antitumor
      activities against Ehrlich carcinoma and Sarcoma 180 (S180) were evaluated. In
      the schedule assayed, the derivates where X = OH and X = NO2 injected i.p. in
      mice at a total dose level of 10 and 30 mg/kg respectively caused a significant
      inhibition of ascitic S180 growth, and at a dose of 25 mg/kg inhibited the growth
      of Ehrlich carcinoma. The derivates where X = H and X = OCH3 did not show
      activity. There are no significant changes of hematopoietic parameters of the
      derivatives in this treatment. These data suggest that the presence of more polar
      substituents, NO2 and OH, strongly increases the antitumor activity of this class
      of compounds.

PMID- 9147620
TI  - [A consideration on the concept of health].

PMID- 9147618
TI  - In vitro evaluation of temozolomide combined with X-irradiation.
AB  - The in vitro cytotoxicity of 8-carbamoyl-3-methylimidazo [5,1-d]-1,2,3,5
      tetrazine-4(3H)-one (temozolomide) with concurrent X-irradiation was examined in
      a human glioblastoma cell line (U373MG) as a potential radio-chemotherapeutic
      treatment for malignant glioma. The combination was also examined in a human
      colorectal adenocarcinoma (Mawi) which had 100-fold greater O6-alkylguanine-DNA
      alkyltransferase (AGT) activity, a DNA-repair protein which confers resistance to
      temozolomide. A comparison of IC50 values indicated U373MG to be over 32-fold
      more sensitive to temozolomide than Mawi, but slightly more resistant to X
      irradiation (p < 0.035; unpaired two-tailed t-test). Temozolomide and X
      irradiation proved largely additive in U373MG by isobologram analysis (50% iso
      effect) and the addition of 10 microM temozolomide to 1-2 Gy of X-irradiation
      increased cell kill by 2.5- to 3.0-fold. However, the combination was
      antagonistic in Mawi: an effect attributed to AGT induction by X-irradiation as
      the antagonism was removed by co-incubation with the AGT inhibitor O6
      benzylguanine (O6-BG 1 microM; 24 h). O6-BG did not affect the radiation dose
      response curve, but significantly increased temozolomide cytotoxicity (p <
      0.015). In conclusion, the combination of temozolomide with radiation is at best
      additive, but could nonetheless by of considerable therapeutic benefit in glioma,
      particularly if administered for prolonged periods. If AGT induction compromises
      the efficacy of this therapy, it may be circumvented with an appropriate
      inhibitor such as O6-BG.

PMID- 9147619
TI  - Proceedings of the 1st Chromosome 6 Sequencing Meeting. Hinxton, England, March
      20, 1996.

PMID- 9147621
TI  - Bibliography. Current world literature. Biochemical engineering.

PMID- 9147622
TI  - Proceedings of the IV International Congress for Endosurgery in Children.
      Orlando, Florida, May 17-20, 1995.

PMID- 9147623
TI  - Differentiation and gene regulation.

PMID- 9147624
TI  - Allergy--A Disease of Modern Society. Proceedings of the 21st Symposium of the
      Collegium Internationale Allergolgicum. Salzburg, Austria, September 6-11, 1996.

PMID- 9147625
TI  - Novel approaches to cancer prevention. Proceedings of a workshop. Lausanne,
      Switzerland, July 11-13, 1996.

PMID- 9147626
TI  - Re-using disposables intended for single use.

PMID- 9147627
TI  - [A possible biological function of cadmium as a calcium analog].

PMID- 9147628
TI  - [Molecular genetic mechanisms of regulating activity of the estS gene in
      transgenic Drosophila].

PMID- 9147629
TI  - [Effect of melatonin and epithalamin on life span and lipid peroxidation in
      Drosophila melanogaster].

PMID- 9147630
TI  - [Role of potassium channels in endothelium-dependent relaxation of the rat
      mesenteric artery].

PMID- 9147631
TI  - [Adapting to physical load increases resistance of the heart to the damaging
      effect of adrenaline and calcium].

PMID- 9147632
TI  - [Morphological characteristics of jerboa (Dipodidae) skin cover].

PMID- 9147633
TI  - [Energy and metabolic intercellular interaction in the growth region of
      Neurospora crassa].

PMID- 9147634
TI  - [Effect of melatonin and epithalamin on the antioxidant defense system activity
      in rats].

PMID- 9147635
TI  - [Thrombolytic and antithrombotic effect of Paeonia anomala extract at low
      concentrations].

PMID- 9147636
TI  - High throughput parallel analysis of hundreds of patient samples for more than
      100 mutations in multiple disease genes.
AB  - As more mutations are identified in genes of known sequence, there is a crucial
      need in the areas of medical genetics and genome analysis for rapid, accurate and
      cost-effective methods of mutation detection. We have developed a multiplex
      allele-specific diagnostic assay (MASDA) for analysis of large numbers of samples
      (> 500) simultaneously for a large number of known mutations (> 100) in a single
      assay. MASDA utilizes oligonucleotide hybridization to interrogate DNA sequences.
      Multiplex DNA samples are immobilized on a solid support and a single
      hybridization is performed with a pool of allele-specific oligonucleotide (ASO)
      probes. Any probes complementary to specific mutations present in a given sample
      are in effect affinity purified from the pool by the target DNA. Sequence
      specific band patterns (fingerprints), generated by chemical or enzymatic
      sequencing of the bound ASO(s), easily identify the specific mutation(s). Using
      this design, in a single diagnostic assay, we tested samples for 66 cystic
      fibrosis (CF) mutations, 14 beta-thalassemia mutations, two sickle cell anemia
      (SCA) mutations, three Tay-Sachs mutations, eight Gaucher mutations, four
      mutations in Canavan disease, four mutations in Fanconi anemia, and five
      mutations in BRCA1. Each mutation was correctly identified. Finally, in a blinded
      study of 106 of these mutations in > 500 patients, all mutations were properly
      identified. There were no false positives or false negatives. The MASDA assay is
      capable of detecting point mutations as well as small insertion or deletion
      mutations. This technology is amenable to automation and is suitable for
      immediate utilization for high-throughput genetic diagnostics in clinical and
      research laboratories.

PMID- 9147637
TI  - Destabilization of CAG trinucleotide repeat tracts by mismatch repair mutations
      in yeast.
AB  - To examine the genetic factors that affect the stability of disease-associated
      trinucleotide repeats, we have assessed the stability of CAG repeats in yeast
      strains with mutations in the mismatch repair system. We have found that both
      pms1 and msh2 mutations destabilize repeat tracts. Destabilization is evidenced
      both by the increased frequency of repeat length changes and in the pattern of
      changes that are observed. In wild-type cells repeats are relatively stable when
      CAG serves as the lagging strand template but relatively unstable when CTG serves
      as the lagging strand template. Large contractions in repeat length are the most
      common change. In pms1 and msh2 mutants the relatively stable tracts incur more
      tract length changes. In addition, many small deletions and some small additions,
      most often of one repeat unit, are frequent in repeats of the stable orientation.
      These small changes also are seen as a new class of events that occur in repeats
      in the unstable orientation. The results show that in yeast the mismatch repair
      system prevents small changes from occurring but cannot prevent larger changes
      from occurring.

PMID- 9147638
TI  - Disruption of the clathrin heavy chain-like gene (CLTCL) associated with features
      of DGS/VCFS: a balanced (21;22)(p12;q11) translocation.
AB  - The smallest region of deletion overlap in the patients we have studied defines a
      DIGeorge syndrome/velocardiofacial syndrome (DGS/VCFS) minimal critical region
      (MDGCR) of approximately 250 kb within 22q11. A de novo constitutional balanced
      translocation has been identified within the MDGCR. The patient has some features
      which have been reported in individuals with DGS/VCFS, including: facial
      dysmorphia, mental retardation, long slender digits and genital anomalies. We
      have cloned the breakpoint of his translocation and shown that it interrupts the
      clathrin heavy chain-like gene (CLTCL) within the MDGCR. The breakpoint of the
      translocation partner is in a repeated region telomeric to the rDNA cluster on
      chromosome 21p. Therefore, it is unlikely that the patient's findings are caused
      by interruption of sequences on 21p. The chromosome 22 breakpoint disrupts the 3'
      coding region of the CLTCL gene and leads to a truncated transcript, strongly
      suggesting a role for this gene in the features found in this patient. Further,
      the patient's partial DGS/VCFS phenotype suggests that additional features of
      DGS/VCFS may be attributed to other genes in the MDGCR. Thus, haploinsufficiency
      for more than one gene in the MDGCR may be etiologic for DGS/VCFS.

PMID- 9147639
TI  - Perinatal lethality and multiple craniofacial malformations in MSX2 transgenic
      mice.
AB  - MSX2 is a homeodomain transcription factor that has been implicated in
      craniofacial morphogenesis on the basis of its expression pattern during mouse
      development and the finding of a missense mutation (P148H) in humans affected
      with Boston-type craniosynostosis. We have generated transgenic mice carrying a
      34 kb DNA fragment encompassing a human MSX2 gene encoding either wild-type or
      mutant (P148H) MSX2. Inheritance of either transgene resulted in perinatal
      lethality and multiple craniofacial malformations of varying severity, including
      mandibular hypoplasia, cleft secondary palate, exencephaly, and median facial
      cleft, which are among the severe craniofacial malformations observed in humans.
      Transgenic mice also manifested aplasia of the interparietal bone and decreased
      ossification of the hyoid. Transgene-induced malformations involved cranial
      neural-crest derivatives, were characterized by a deficiency of tissue, and were
      similar to malformations associated with embryonic exposure to ethanol or
      retinoic acid, teratogens that cause increased cell death. Together with previous
      observations implicating MSX2 expression in developmentally-programmed cell
      death, these results suggest that wild-type levels of MSX2 activity may establish
      a balance between survival and apoptosis of neural crest-derived cells required
      for proper craniofacial morphogenesis.

PMID- 9147640
TI  - Functional analysis of paired box missense mutations in the PAX6 gene.
AB  - Mutations in the human PAX6 gene produce various phenotypes, including aniridia,
      Peters' anomaly, autosomal dominant keratitis and familial foveal dysplasia. The
      various phenotypes may arise from different mutations in the same gene. To test
      this theory, we performed a functional analysis of two missense mutations in the
      paired domain: the R26G mutation, previously reported in a case of Peters'
      anomaly, and an unreported I87R mutation, which we identified in a patient with
      aniridia. While both the R26 and the I87 positions are conserved in the paired
      boxes of all known PAX genes, X-ray crystallography has shown that only R26 makes
      contact with DNA. We showed that the R26G mutant failed to bind a subset of
      paired domain binding sites but, surprisingly, bound other sites and successfully
      transactivated promoters containing those sites. In contrast, the I87R mutant had
      lost the ability to bind DNA at all tested sites and failed to transactivate
      promoters. Our data support the haploid-insufficiency hypothesis of aniridia, and
      the hypothesis that R26G is a hypomorphic allele.

PMID- 9147641
TI  - Imprinted segments in the human genome: different DNA methylation patterns in the
      Prader-Willi/Angelman syndrome region as determined by the genomic sequencing
      method.
AB  - A deletion of 15q11-q13 and uniparental disomy 15 lead to Prader-Labhart-Willi
      syndrome (PWS) or Angelman syndrome (AS) because this region contains genes
      expressed exclusively from the paternal (PWS) or maternal (AS) chromosome,
      respectively. DNA methylation plays a role in the control of imprinted gene
      expression, but so far only a few 5'-CG-3' dinucleotides within the recognition
      sites of the methylation sensitive enzymes have been studied. As part of a study
      on DNA methylation patterns in the human genome, we have applied the bisulfite
      protocol of genomic sequencing to study all 5'-CG-3' dinucleotides around exon 1
      of SNRPN and at the D15S63 locus, which contains a start site for alternative
      SNRPN transcripts possibly involved in imprint switching during gametogenesis. At
      least 17 PCR products derived from single chromosomes of normal individuals as
      well as PWS and AS patients have been sequenced. We have found that cytosine
      residues outside 5'-CG-3' dinucleotides are always unmethylated. However, > 96%
      of all of the 23 5'-CG-3' dinucleotides around SNRPN exon 1 are methylated on the
      maternal chromosome and completely devoid of methylation on the paternal
      chromosome. This finding is in contrast to the D15S63 locus, where only the two
      Cfol/Hhal sites are methylated on the maternal chromosome at the same frequency
      as seen for the SNRPN segment. At the other five 5'-CG-3' dinucleotides,
      differential methylation is less pronounced, i.e. 45-70% on the maternal
      chromosome and 5-14% on the paternal chromosome. The differences between SNRPN
      and D15S63 methylation may reflect different biological functions of the
      alternative SNRPN transcripts. The systematic investigation of 5'-CG-3'
      methylation patterns as reported here will provide the basis for a PCR-based
      methylation test to diagnose PWS and AS.

PMID- 9147642
TI  - Association of the steroid synthesis gene CYP11a with polycystic ovary syndrome
      and hyperandrogenism.
AB  - Biochemical data implicate an underlying disorder of androgen biosynthesis and/or
      metabolism in the aetiology of polycystic ovary syndrome (PCOS). We have examined
      the segregation of the genes coding for two key enzymes in the synthesis and
      metabolism of androgens, cholesterol side chain cleavage (CYP11a) and aromatase
      (CYP19), with PCOS in 20 multiply-affected families. All analyses excluded CYP19
      cosegregation with PCOS, demonstrating that this locus is not a major determinant
      of risk for the syndrome. However, our results provide evidence for linkage to
      the CYP11a locus (NPL score = 3.03, p = 0.003). Parametric analysis using a
      dominant model suggests genetic heterogeneity, generating a maximum HLOD score of
      2.7 (alpha = 0.63). An association study of 97 consecutively identified Europids
      with PCOS and matched controls demonstrates significant allelic association of a
      CYP11a 5' UTR pentanucleotide repeat polymorphism with hirsute PCOS subjects (p =
      0.03). A strong association was also found between alleles of this polymorphism
      and total serum testosterone levels in both affected and unaffected individuals
      (p = 0.002). Our data demonstrate that variation in CYP11a may play an important
      role in the aetiology of hyperandrogenaemia which is a common characteristic of
      polycystic ovary syndrome.

PMID- 9147643
TI  - Survey of maximum CTG/CAG repeat lengths in humans and non-human primates: total
      genome scan in populations using the Repeat Expansion Detection method.
AB  - Repeat Expansion Detection (RED) is an efficient and simple method for detecting
      repeat expansions in the human genome, including expansion mutations resulting in
      disease. Here we report the first population survey of CTG/CAG repeat lengths in
      humans using the RED method; we have determined maximum CTG/CAG repeat length in
      244 individuals from six human populations: Danes, Chinese, Japanese, Rondonian
      Surui, Maya and Mbuti/Biaka Pygmies. We have also sampled a number of non-human
      primates including eight orang-utans (Pongo pygmaeus), seven gorillas (Gorilla
      gorilla), seven pygmy chimpanzees (Pan paniscus), 13 common chimpanzees (Pan
      troglodytes) and three Hylobatidae (one Hylobates lar, one H.klossii, and one
      H.syndactylus). Our results demonstrate the existence of significant variation in
      the sizes and frequencies of the longest CTG/CAG repeat length seen per
      individual both within and between human populations. The population differences
      argue that overall mutation rates at CTG/CAG repeat loci are sufficiently low
      that mutation does not obliterate the effect of random genetic drift and clearly
      indicate that population stratification could occur in disease association
      studies using the RED method. No significant differences were detected among the
      non-human primates sampled. Our results also show that both common chimpanzees
      and pygmy chimpanzees (bonobos) are polymorphic for maximum length of any CTG/CAG
      repeats while no variation was found for gorillas and orang-utans.

PMID- 9147644
TI  - Immunocytochemical localization of the Menkes copper transport protein (ATP7A) to
      the trans-Golgi network.
AB  - We have generated polyclonal antibodies against the amino-terminal third of the
      Menkes protein (ATP7A; MNK) by immunizing rabbits with a histidine-tagged MNK
      fusion construct containing metal-binding domains 1-4. The purified antibodies
      were used in Western analysis of cell lysates and in indirect immunofluorescence
      experiments on cultured cells. On Western blots, the antibodies recognized the
      approximately 165 kDa MNK protein in CHO cells and human fibroblasts. No MNK
      signal could be detected in fibroblasts from a patient with Menkes disease or in
      Hep3B hepatocellular carcinoma cells, confirming the specificity of the
      antibodies. Immunocytochemical analysis of CHO cells and human fibroblasts showed
      a distinct perinuclear signal corresponding to the pattern of the Golgi complex.
      This staining pattern was similar to that of alpha-mannosidase II which is a
      known resident enzyme of the Golgi complex. Using brefeldin A, a fungal inhibitor
      of protein secretion, we further demonstrated that the MNK protein is localized
      to the trans-Golgi network. This data provides direct evidence for a subcellular
      localization of the MNK protein which is similar to the proposed vacuolar
      localization of Ccc2p, the yeast homolog of MNK and WND (ATP7B), the Wilson
      disease gene product. In light of the proposed role of MNK both in subcellular
      copper trafficking and in copper efflux, these data suggest a model for how these
      two processes are linked and represent an important step in the functional
      analysis of the MNK protein.

PMID- 9147645
TI  - Mutation analysis provides additional proof that mottled is the mouse homologue
      of Menkes' disease.
AB  - Menkes' disease (MD) and occipital horn syndrome (OHS) are allelic X-linked
      disorders caused by mutations in the copper ion transporting ATPase, ATP7A.
      Genetic, phenotypic and biochemical data suggest that mottled mutants in the
      mouse, which range in severity and phenotype, are caused by mutations in Atp7a,
      the mouse homologue of ATP7A. As the only causal mutation in Atp7a has been
      reported in one very mild allele thought to be a model for OHS, Atp7aMo-blo
      (mottled blotchy), we sequenced the entire 4.5 kb coding region of three other
      mottled mutants, two of which are thought to be models for classical MD (AtpaMo
      br, AtpaMo-13H) and one with a slightly milder phenotype (Atp7aMo-vbr). Although
      no causal mutation was found in Atp7aMo-13H, mutations which can be predicted to
      affect Atp7a function were identified in Atp7aMo-br and Atp7aMo-vbr. A 6 bp
      deletion of nucleotides 2478-2483, which can be predicted to affect the correct
      processing of the protein, was found in Atp7aMo-br and an A3189-->C nucleotide
      change, which results in lysine-->threonine amino acid substitution in the
      phosphorylation domain, was found in Atp7aMo-vbr. Thus we provide further proof
      that mottled mutants will provide excellent models for MD as well as OHS.

PMID- 9147646
TI  - The mottled mouse as a model for human Menkes disease: identification of
      mutations in the Atp7a gene.
AB  - Mutations in the Atp7a gene, the mouse homologue of the MNK (ATP7A) gene, have
      been suggested to be responsible for the mottled phenotype. To date, despite
      considerable effort, changes associated with the mottled mutations have been
      detected in only two such mutants. In this study, we identify changes in the
      level of Atp7a transcript and mutations which could explain the mottled phenotype
      in nine out of the 10 mutants analysed. The fluorescence-assisted mismatch
      analysis method used here has proved particularly well suited for mRNA scanning
      of heterozygous carrier animals, because of its ability to detect mutations even
      in the presence of an excess of wild-type mRNA. The three new underlying
      mutations identified at the Atp7a locus include a splice mutation and two
      missense mutations. While the spectrum of mutations detected in the Atp7a murine
      gene provides an explanation for at least part of the wide phenotypic variation
      observed in mottled mutant mice, there is a singular absence of deletions which
      are associated with a sizeable fraction of human Menkes syndrome cases.

PMID- 9147647
TI  - FMR2 expression in families with FRAXE mental retardation.
AB  - Normal individuals express the two alternative transcripts, FMR2 and Ox19, from
      the FRAXE-associated CpG island. Molecular analysis of the Ox19 transcript
      suggests that it is a truncated isoform of the FMR2 gene with an alternative 3'
      end. Both isoforms showed a similar pattern of expression, with the Ox19 isoform
      expressed at a much lower level. Fibroblasts, chorionic villi and hair roots
      showed the highest level of FMR2 expression, whole blood cells and amniocytes
      showed very low expression, and the transcript was not detected in lymphoblasts.
      Fibroblasts of 11 individuals from seven families segregating FRAXE were assayed
      for FMR2 expression and FRAXE CpG island methylation. A man with an unmethylated
      expansion of 0.6 kb expressed FMR2 and represents a pre-mutation carrier. All
      chromosomes with FRAXE CCG expansions of 0.8 kb or greater were fully methylated
      and did not express the FMR2 gene, analogous to the mechanism of silencing the
      FMR1 gene in carriers of the FRAXA full mutation. The boundary between FRAXE pre
      mutation and FRAXE full mutation is between 0.7 and 0.8 kb. Two men with absence
      of FMR2 expression in fibroblasts were not mentally impaired, suggesting that IQ
      in some men with FRAXE full mutation may remain within the normal range. Although
      molecular tools to study FRAXE non-specific mental retardation are now available,
      further psychometric and molecular studies are needed to characterize the effect
      of the FRAXE full mutation for the purpose of genetic counselling.

PMID- 9147648
TI  - Molecular phenotype of a human lymphoblastoid cell-line homoplasmic for the np
      7445 deafness-associated mitochondrial mutation.
AB  - We have studied mitochondrial gene expression and metabolic function in a human
      lymphoblastoid cell-line homoplasmic for the np 7445, deafness-associated
      mitochondrial DNA mutation. The mutation maps to the 3' termini of the oppositely
      oriented genes encoding cytochrome oxidase subunit I (COI) and tRNA-ser(UCN). In
      comparison with control lymphoblastoid cells, we detected a marked depletion (>
      60%) of tRNA-ser(UCN). There was, however, no significant impairment of
      respiratory function, no alteration to the structure or abundance of COI mRNA or
      its precursors, and no detectable abnormality of mitochondrial protein synthesis.
      We also found considerable tissue-variation in the abundance of tRNA-ser(UCN). We
      propose that the tissue-specific phenotype associated with this mutation results
      from an inherent deficiency in the processing of the mutant pre-tRNA, that
      becomes limiting for protein synthesis only in a restricted set of cells of the
      auditory system in which the tRNA is, for other reasons, already at a critically
      low level.

PMID- 9147649
TI  - Mosaic methylation of the repeat unit of the human ribosomal RNA genes.
AB  - The pattern of methylation in human genes for 18S and 28S ribosomal RNA has been
      investigated using methylation-sensitive restriction enzymes. We find that the
      transcribed region of the repeat unit is predominantly unmethylated, in agreement
      with previous studies. In contrast the non-transcribed spacer, which makes up the
      majority of the 43 kb repeat unit, is highly methylated in blood cell DNA. The
      boundaries between methylated and non-methylated domains appear to be relatively
      sharp, and occur approximately 1.5 kb upstream of the 5' edge of the proximal
      promoter and approximately 1.0 kb downstream of the 3' end of the transcribed
      region. A small proportion of all repeat units are methylated throughout the
      transcribed region, and may represent silent genes. The coincidence between the
      methylation pattern, the transcription pattern and other features of the repeat
      unit has implications for our understanding of the mechanism by which patterns of
      DNA methylation are generated.

PMID- 9147650
TI  - Pituitary homeobox 2, a novel member of the bicoid-related family of homeobox
      genes, is a potential regulator of anterior structure formation.
AB  - Genetic analysis of mouse mutants has demonstrated the importance of the homeobox
      genes Rpx, Lhx3 and Pit1 for anterior pituitary gland development. Pit1 mutations
      have also been identified in several human families with multiple pituitary
      hormone deficiencies. To identify additional homeobox regulators of pituitary
      development, we screened an adult pituitary gland cDNA library for homeobox
      sequences. Here, we report the identification of a novel bicoid-related
      homeodomain gene expressing two alternatively spliced mRNA products, which encode
      proteins of 271 and 317 amino acids, respectively. The proteins have been named
      Ptx2a and Ptx2b since they are highly related to Ptx1/P-OTX. Ptx2 is expressed in
      both developing and adult pituitary gland, eye and brain tissues, suggesting an
      important role in development and maintenance of anterior structures. Ptx2 was
      mapped close to Egf on mouse chromosome 3, in a region having extensive synteny
      homology with HSA 4q. These data make the human Ptx2 homologue a candidate gene
      for Rieger syndrome, an autosomal-dominant disorder with variable craniofacial,
      dental, eye and pituitary anomalies.

PMID- 9147651
TI  - A novel human homologue of the Drosophila frizzled wnt receptor gene binds
      wingless protein and is in the Williams syndrome deletion at 7q11.23.
AB  - Williams syndrome (WS) is a developmental disorder with a characteristic
      personality and cognitive profile that is associated, in most cases, with a 2 Mb
      deletion of part of chromosome band 7q11.23. By applying CpG island cloning
      methods to cosmids from the deletion region, we have identified a new gene,
      called FZD3. Dosage blotting of DNA from 11 WS probands confirmed that it is
      located within the commonly deleted region. Sequence comparisons revealed that
      FZD3, encoding a 591 amino acid protein, is a novel member of a seven
      transmembrane domain receptor family that are mammalian homologs of the
      Drosophila tissue polarity gene frizzled. FZD3 is expressed predominantly in
      brain, testis, eye, skeletal muscle and kidney. Recently, frizzled has been
      identified as the receptor for the wingless (wg) protein in Drosophila. We show
      that Drosophila as well as human cells, when transfected with FZD3 expression
      constructs, bind Wg protein. In mouse, the wg homologous Wnt1 gene is involved in
      early development of a large domain of the central nervous system encompassing
      much of the midbrain and rostral metencephalon. The potential function of FZD3 in
      transmitting a Wnt protein signal in the human brain and other tissues suggests
      that heterozygous deletion of the FZD3 gene could contribute to the WS phenotype.

PMID- 9147652
TI  - Linkage mapping of benign familial infantile convulsions (BFIC) to chromosome
      19q.
AB  - Benign familial infantile convulsions (BFIC) are an autosomal-dominant epileptic
      syndrome characterized by an age of onset within the first year of life. Although
      they were first reported in families of Italian descent, BFIC have also been
      described in non-Italian families. We have mapped the BFIC gene to chromosome 19
      by linkage analysis in five Italian families with a maximum two-point lod score
      of 6.36 at D19S114; maximum multipoint lod scores > 8 were obtained for the
      interval D19S250-D19S245. BFIC are therefore the third idiopathic partial
      epileptic syndrome to be mapped on the human genome.

PMID- 9147653
TI  - Molecular and phenotypic variation in patients with severe Hunter syndrome.
AB  - Severe Hunter syndrome is a fatal X-linked lysosomal storage disorder caused by
      iduronate-2-sulphatase (IDS) deficiency. Patients with complete deletion of the
      IDS locus often have atypical phenotypes including ptosis, obstructive sleep
      apnoea, and the occurrence of seizures. We have used genomic DNA sequencing to
      identify several new genes in the IDS region. DNA deletion patients with atypical
      symptoms have been analysed to determine whether these atypical symptoms could be
      due to involvement of these other loci. The occurrence of seizures in two
      individuals correlated with a deletion extending proximal of IDS, up to and
      including part of the FMR2 locus. Other (non-seizure) symptoms were associated
      with distal deletions. In addition, a group of patients with no variant symptoms,
      and a characteristic rearrangement involving a recombination between the IDS gene
      and an adjacent IDS pseudogene (IDS psi), showed normal expression of loci distal
      to IDS. Together, these results identify FMR2 as a candidate gene for seizures,
      when mutated along with IDS.

PMID- 9147654
TI  - HIP-I: a huntingtin interacting protein isolated by the yeast two-hybrid system.
AB  - We report the discovery of the huntingtin interacting protein I (HIP-I) which
      binds specifically to the N-terminus of human huntingtin, both in the two-hybrid
      screen and in in vitro binding experiments. For the interaction in vivo, a
      protein region downstream of the polyglutamine stretch in huntingtin is
      essential. The HIP1 cDNA isolated by the two-hybrid screen encodes a 55 kDa
      fragment of a novel protein. Using an affinity-purified polyclonal antibody
      raised against recombinant HIP-I, a protein of 116 kDa was detected in brain
      extracts by Western blot analysis. The predicted amino acid sequence of the HIP-I
      fragment exhibits significant similarity to cytoskeleton proteins, suggesting
      that HIP-I and huntingtin play a functional role in the cell filament networks.
      The HIP1 gene is ubiquitously expressed in different brain regions at low level.
      HIP-I is enriched in human brain but can also be detected in other human tissues
      as well as in mouse brain. HIP-I and huntingtin behave almost identically during
      subcellular fractionation and both proteins are enriched in the membrane
      containing fractions.

PMID- 9147655
TI  - Missense mutation clustering in the survival motor neuron gene: a role for a
      conserved tyrosine and glycine rich region of the protein in RNA metabolism?
AB  - The Survival Motor Neuron (SMN) gene shows deletions in the majority of patients
      with Spinal Muscular Atrophy (SMA), a disease of motor neuron degeneration. To
      date only two missense mutations have been reported in SMN in patients with SMA.
      The fact that no SMN-homologues have been forthcoming from data-base searching
      has resulted in a lack of hypotheses concerning the structural and functional
      consequences of these mutations. Recently SMN has been shown to interact with
      heterogeneous nuclear ribonucleoproteins (hnRNPs) suggesting a role in mRNA
      metabolism. We describe a novel missense mutation and the subsequent
      identification of a triplicated tyrosine-glycine (Y-G) peptide sequence at the C
      terminal of SMN which encompasses each of the three predicted amino acid sequence
      substitutions. We have identified apparent orthologues of SMN in Caenorhabditis
      elegans and Schizosaccharomyces pombe. These sequences retain the highly
      conserved Y-G motif and provide additional support for a role of SMN in mRNA
      metabolism.

PMID- 9147656
TI  - The evolutionary distribution and structural organization of the homeobox
      containing repeat D4Z4 indicates a functional role for the ancestral copy in the
      FSHD region.

PMID- 9147657
TI  - Luminal and non-luminal non-competitive inhibitor binding sites on the nicotinic
      acetylcholine receptor.
AB  - The nicotinic acetylcholine receptor presents two very well differentiated
      domains for ligand binding that account for different cholinergic properties. In
      the hydrophilic extracellular region of the alpha subunit exist the binding sites
      for agonists such as the neurotransmitter acetylcholine, which upon binding
      trigger the channel opening, and for competitive antagonists such as d
      tubocurarine, which compete for the former inhibiting its pharmacological action.
      For non-competitive inhibitors, a population of low-affinity binding sites have
      been found at the lipid-protein interface of the nicotinic acetylcholine
      receptor. In addition, at the M2 transmembrane domain, several high-affinity
      binding sites have been found for non-competitive inhibitors such as
      chlorpromazine, triphenylmethylphosphonium, the local anaesthetic QX-222 and the
      hydrophobic probe trifluoromethyl-iodophenyldiazirine. They are known as luminal
      binding sites. Although the local anaesthetic meproadifen seems to be located
      between the hydrophobic domains M2-M3, this locus is considered to form part of
      the channel mouth, thus this site can also be called a luminal binding site. In
      contraposition, experimental evidences support the hypothesis of the existence of
      other high-affinity binding sites for non-competitive inhibitors located not at
      the channel lumen, but at non-luminal binding domains. Among them, we can quote
      the binding site for quinacrine, which is located at the lipid-protein interface
      of the alpha M1 domain, and the binding site for ethidium, which is believed to
      interact with the wall of the vestibule very far away from both the lumen channel
      and the lipid membrane surface. The aim of this review is to discuss these recent
      findings relative to both structurally and functionally relevant aspects of non
      competitive inhibitors of the nicotinic acetylcholine receptor. We will put
      special emphasis on the description of the localization of molecules with non
      competitive antagonist properties that bind with high-affinity to luminal and non
      luminal domains. The information described herein was principally obtained by
      means of methods such as photolabelling and site-directed mutagenesis in
      combination with patch-clamp. Our laboratory has contributed with data obtained
      by using biophysical approaches such as paramagnetic electron spin resonance and
      quantitative fluorescence spectroscopy.

PMID- 9147658
TI  - Regulation of targeting signals in membrane proteins. [review].
AB  - Membrane proteins can contain short sequence motifs that determine their
      intracellular location, either by a retention or a retrieval mechanism. In both
      cases the targeting signal is essentially a specific binding site for other
      proteins that effect the localization. The folding of targeting motifs is often
      robust leading to a dominant effect in molecular cut and paste experiments
      designed to identify them. However regulation can also occur, allowing a single
      membrane protein to express different targeting signals at different locations in
      the cell. Regulation can be achieved by phosphorylation of the cytoplasmic domain
      leading to changes in binding affinity for effector proteins, or by masking of
      the targeting signal by complex formation.

PMID- 9147659
TI  - Localization of the gene for the human serotonin 5-HT(2B) receptor to chromosome
      2.
AB  - A 483 bp Bgl II/Sal I repeat free fragment was isolated from the vector
      containing the human serotonin 5-HT(2B) receptor. This fragment contained part of
      the coding sequence located within the last exon and the entire 3'-non-translated
      region. It was used to probe, by Southern blots, Pst I digested DNA from a series
      of 20 rodent-human somatic cell hybrid lines, each of which contained different
      complements of human chromosomes. This 5-HT(2B) receptor probe showed
      hybridization to a 2-7 kb Pst I fragment which revealed 100 percent concordance
      with location of the gene for this 5-HT receptor variant at chromosome 2.

PMID- 9147660
TI  - Membrane insertion, processing, and topology of cystic fibrosis transmembrane
      conductance regulator (CFTR) in microsomal membranes.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated
      C1(-) channel. Malfunction of CFTR causes cystic fibrosis (CF). CFTR belongs to
      an ATP-binding cassette (ABC) transporter superfamily which includes P
      glycoprotein (Pgp), the molecule that is responsible for multidrug resistance in
      cancer cells. P-glycoprotein molecules have been suggested to have more than one
      topology and function. In this study, we analysed the early stages of membrane
      insertion, processing, and topology of human CFTR using rabbit reticulocyte
      lysate and wheat germ extract translation systems supplemented with canine
      pancreatic microsomal membranes. Our results suggest that CFTR contains an
      uncleavable signal sequence and its membrane targeting and insertion may depend
      on the signal recognition particle (SRP) and SRP receptor. The topology of CFTR
      in microsomal membranes is the same as the one predicted based on hydropathy plot
      analysis. These results, together with our previous findings on Pgp, indicate
      that (1) the topologies of mammalian ABC transporters can be dissected and
      studied using protein fusion chimeras in a cell-tree system; and (2) the membrane
      targeting and insertion of CFTR and Pgp may take the same pathway, i.e., the SRP
      dependent pathway, but the membrane folding mechanism of these two proteins in
      microsomal membranes is probably different.

PMID- 9147661
TI  - Combinatorial mutagenesis analysis of residues in the channel constriction loop
      L3 and neighbouring beta-strands in the LamB glycoporin of Escherichia coli.
AB  - Members of the LamB family of sugar-selective porins (glycoporins) are beta
      barrel proteins in the outer membrane of Gram-negative bacteria. To study the
      determinants of structure and sugar selectivity, 68 non-identical single amino
      acid substitutions were introduced into the stretch of sequence consisting of
      residues 106 through 125 in Escherichia coli LamB. This region includes all bar
      one residue of the channel constriction loop L3 and extends into the
      transmembrane beta 6 strand in the LamB structure. Mutants were assayed for
      dextrin utilization, starch binding, A binding, monoclonal antibody binding and
      for qualitative changes in protein expression. The importance of the L3 amino
      acids was emphasized by the observation that only four residues permitted a
      majority of neutral substitutions. Changes to the channel constriction zone
      strongly affected sugar binding yet no single amino acid change of residues
      exposed to the channel lumen caused a complete defect in maltodextrin utilization
      (i.e. were still Dex+). Substitutions in the L3 loop did not affect phage lambda
      binding, except one change at residue 122, nor changed recognition by anti-LamB
      antibodies specific for surface epitopes, consistent with the lack of a role of
      L3 residues in surface receptor function. In marked contrast, four substitutions
      in transmembrane strand beta 5 resulted in a Dex- phenotype and gross changes in
      protein properties, indicating the significance of beta 5 in the architecture of
      LamB.

PMID- 9147662
TI  - The effect of N-terminal fragments of immunophilin on phospholipid composition of
      rat brain.
AB  - Rat brain slices have been incubated in the presence of water-soluble synthetic
      peptide fragments corresponding to residues 1-9 and 1-15 of the N-terminus of
      immunophilin and the effects on the phospholipid composition examined. During a 2
      h incubation in the presence of 1 nM, 0-1 mu M and 10 mu M concentrations of the
      peptides there were significant and dose-dependent decreases in the amounts of
      phosphatidylcholine and phosphatidylethanolamine and increases in the amounts of
      phosphatidylserine and, to a lesser extent, phosphatidylinositol, cardiolipin and
      lysophosphatidylcholine. The overall decrease in the neutral phospholipids and
      increase in the acidic phospholipids tended to counteract any change in the
      phospholipid composition of the tissue. The results are discussed in terms of the
      possible effects of immunophilin on modulating phospholipid turnover in brain
      cell membranes.

PMID- 9147664
TI  - [Strategies for women with cardio-vascular disease].

PMID- 9147663
TI  - A method for determining transmembrane protein structure.
AB  - A simple and rapid protein chemical approach for determining the transmembrane
      structure of membrane proteins is described. The method involves single
      substitutions of consecutive amino acid residues, within putative transmembrane
      segments, to cysteine. This is followed by the analysis of their susceptibility
      to modification by maleimides with different physico-chemical properties.
      Fluorescein-5-maleimide (FM), being hydrophilic, modified only residues located
      in the aqueous environment, while the hydrophobic reagent, benzophenone-4
      maleimide (BM) modified residues exposed to the lipid phase. These probes are
      large enough to cause an increase in the molecular weight of relatively small
      membrane proteins or polypeptide fragments, which is detectable by SDS-PAGE.
      Modification by much smaller probes, such as N-ethylmaleimide (NEM), could also
      be monitored indirectly by the ability to prevent SDS-solubilized protein from
      being modified with fluorescein-5-maleimide. The approach is demonstrated with
      the proteolipid complex of the vacuolar H(+)-ATPase expressed in yeast and with
      the putative Isk K(+)-channel expressed and radiolabelled in E. coli. The
      advantages of this approach are: (1)it is rapid, easy and inexpensive, (2)
      detection of the modification of engineered cysteines is simple, (3) it requires
      only minute quantities of the protein, (4) the protein does not require
      purification, (5) a broad range of maleimides with different physico-chemical
      properties can be used, (6) the structure can be investigated under native
      conditions and does not require protein reconstitution into artificial bilayers.

PMID- 9147665
TI  - [International Congress of Nursing Sciences. Challenges and victories].

PMID- 9147666
TI  - [Patient-oriented care. Meeting the patients' needs].

PMID- 9147667
TI  - [Placing a relative with irreversible dementia. A difficult decision for the
      natural caregivers].

PMID- 9147668
TI  - [Helping suicidal persons by active listening].

PMID- 9147669
TI  - [At the Hull CHSLD consultation is the norm].

PMID- 9147670
TI  - The future of the profession. Assuming our responsibilities to assure new blood.

PMID- 9147671
TI  - [Louisanne Lamothe-Ouellette: a voice for the health information nurses.
      Interview by Marie-Claude Bourdon].

PMID- 9147672
TI  - [Autonomy as seen by the aged].

PMID- 9147673
TI  - [Encouragement for the creative genius of nurses].

PMID- 9147674
TI  - [Self medication. A way to make substance addicts responsible].

PMID- 9147675
TI  - [Nurses with bachelors degrees in a geriatric short-term unit. A step towards
      professional autonomy].

PMID- 9147676
TI  - [A current health service without appointments that relies on the nurse's
      competence].

PMID- 9147677
TI  - [Disturbing behaviors in the geriatric environment. Nurses create new
      instruments].

PMID- 9147678
TI  - [Pediatric palliative home nursing for choice accompaniment].

PMID- 9147679
TI  - [The nursing place for patients with stomas "Mieux vivre". More than technical
      help].

PMID- 9147680
TI  - [The Vallee des Roseaux and the education center for palliative care. The work of
      Sister Odete Lavallee].

PMID- 9147681
TI  - [The program for neurology education. A tangible proof of professional
      engagement].

PMID- 9147682
TI  - [Women vulnerable to depression discover the power of creativity].

PMID- 9147683
TI  - ["Light on love". When young people undertake to promote the wearing of condoms].

PMID- 9147684
TI  - [The intervention of support by peers].

PMID- 9147685
TI  - [Prescription drug insurance. An improvised legal project].

PMID- 9147686
TI  - Molecular characterization of clonal population structure and biogeography of
      arctic apomictic Daphnia from Greenland and Iceland.
AB  - As part of a continuing international project to characterize the population
      genetic (clonal) structure of arctic members of the Daphnia pulex complex, 34
      populations from western Iceland (N = 1373), and 76 populations from western
      Greenland (N = 2917), were surveyed for allozymic variation at six polymorphic
      enzyme loci. Mean clonal richness (+/- SE) was 1.91 +/- 0.19 and 1.50 +/- 0.12
      for Iceland and Greenland populations, respectively. Mean clonal diversity (+/-1
      SE) was 1.20 +/- 0.07 and 1.13 +/- 0.04 for Iceland and Greenland populations,
      respectively. Four widely distributed clones constituted 92.2% of the total
      animals surveyed from Iceland, while three locally abundant clones constituted
      80.1% of the total animals collected primarily from Disko Island, western
      Greenland. Selected populations were screened for mitochondrial (mt)DNA variation
      using PCR-based RFLP analysis of a 2100 bp fragment containing part of the ND4
      and ND5 genes. One mtDNA haplotype was very widespread in both western Greenland
      and western Iceland, although, a number of mutational derivatives were also
      detected. These data indicate the potential for long-distance dispersal of mtDNA
      lineages, of the order of hundreds or thousands of kilometers across the arctic.
      Phylogenetic analysis of the sequence of a 254 base pair (bp) fragment of the
      control region of the mtDNA molecule revealed two major clades one of which
      consisted solely of non-melanic lineages, and the other of which consisted almost
      exclusively of melanic lineages (i.e. one non-melanic lineage also clustered in
      this clade). Sequence divergence between the two clades averaged 7.3%. Both
      mitochondrial analyses did not reveal any distinct intraregional clustering of
      lineages. We discuss our results in reference to previous molecular work done on
      this arctic Daphnia complex, and we attempt to infer phylogeographic patterning
      based on geological/glaciological historical events in this region of the arctic.

PMID- 9147687
TI  - Distribution and abundance of trypanosome (subgenus Nannomonas) infections of the
      tsetse fly Glossina pallidipes in southern Africa.
AB  - Over 10 000 Glossina pallidipes tsetse flies were collected during two field
      studies in the Zambezi Valley, Zimbabwe and one in the Luangwa Valley, Zambia.
      These were screened for mature trypanosome infections and 234 dot-blot
      preparations were made of infected midguts, which were screened using DNA probes
      or PCR with primers specific to different species or types of the trypanosome
      subgenus Nannomonas. Over 70% of midgut infections were successfully identified
      as either Trypanosoma godfreyi, T. simiae or three types of T. congolense,
      savannah, riverine-forest and Kilifi. The relative abundance of species and types
      did not vary significantly between study locations, habitat, season or tsetse age
      or sex, although there were differences between DNA probe and PCR results. Mixed
      species and/or mixed type infections were common and were more often detected
      using PCR. The distribution of infections among flies was highly aggregated, but
      there was no tendency for multiple infections to accumulate in older flies,
      implying that sequential superinfection may be uncommon. Possible explanations
      for these patterns are discussed.

PMID- 9147688
TI  - Amplified fragment length polymorphism (AFLP) fingerprinting of symbiotic fungi
      cultured by the fungus-growing ant Cyphomyrmex minutus.
AB  - A PCR-based fingerprinting technique based on amplified fragment length
      polymorphisms (AFLP) is used to screen symbiotic fungi of the fungus-growing ant
      Cyphomyrmex minutus for genetic differences. AFLP fingerprints reveal several
      fungal 'types' that (a) represent distinct clones propagated vegetatively by the
      ant, or (b) correspond to free-living fungi that may be acquired by the ant.
      Fungal types identified by AFLP fingerprints correspond to vegetative
      compatibility groups established previously, suggesting that vegetative
      compatibility can be used as a crude indicator of genetic differences between
      fungi of C. minutus.

PMID- 9147689
TI  - Dissemination of the strA-strB streptomycin-resistance genes among commensal and
      pathogenic bacteria from humans, animals, and plants.
AB  - Gene transfer within bacterial communities has been recognized as a major
      contributor in the recent evolution of antibiotic resistance on a global scale.
      The linked strA-strB genes, which encode streptomycin-inactivating enzymes, are
      distributed worldwide and confer streptomycin resistance in at least 17 genera of
      gram-negative bacteria. Nucleotide sequence analyses suggest that strA-strB have
      been recently disseminated. In bacterial isolates from humans and animals, strA
      strB are often linked with the suIII sulfonamide-resistance gene and are encoded
      on broad-host-range nonconjugative plasmids. In bacterial isolates from plants,
      strA-strB are encoded on the Tn3-type transposon Tn5393 which is generally borne
      on conjugative plasmids. The wide distribution of the strA-strB genes in the
      environment suggests that gene transfer events between human, animal, and plant
      associated bacteria have occurred. Although the usage of streptomycin in clinical
      medicine and animal husbandry has diminished, the persistence of strA-strB in
      bacterial populations implies that factors other than direct antibiotic selection
      are involved in maintenance of these genes.

PMID- 9147690
TI  - Microsatellite markers for the study of cetacean populations.
AB  - Microsatellites are one of the most important classes of nuclear genetic markers
      and offer many advantages for the study of marine mammals. Here we describe the
      isolation and characterization of 12 cetacean microsatellites which are then
      tested across 30 different cetacean species. For around half the species tested,
      five or more polymorphic loci were identified. Since many species were
      represented by only one or two specimens, this figure is likely to underestimate
      the usefulness of these markers. No relationship was found between microsatellite
      repeat length and proportion of species which gave polymorphic products.

PMID- 9147691
TI  - Identification of highly polymorphic microsatellites in the rhesus macaque Macaca
      mulatta by cross-species amplification.

PMID- 9147692
TI  - PCR primers for harbour seal (Phoca vitulina concolour) microsatellites amplify
      polymorphic loci in other pinniped species.

PMID- 9147693
TI  - Genetic differentiation of continental and island populations of Bombus
      terrestris (Hymenoptera: Apidae) in Europe.
AB  - Ten microsatellite loci and a partial sequence of the COII mitochondrial gene
      were used to investigate genetic differentiation in B. terrestris, a bumble bee
      of interest for its high-value crop pollination. The analysis included eight
      populations from the European continent, five from Mediterranean islands (six
      subspecies altogether) and one from Tenerife (initially described as a colour
      form of B. terrestris but recently considered as a separate species, B.
      canariensis). Eight of the 10 microsatellite loci displayed high levels of
      polymorphism in most populations. In B. terrestris populations, the total number
      of alleles detected per polymorphic locus ranged from 3 to 16, with observed
      allelic diversity from 3.8 +/- 0.5 to 6.5 +/- 1.4 and average calculated
      heterozygosities from 0.41 +/- 0.09 to 0.65 +/- 0.07. B. canariensis showed a
      significantly lower average calculated heterozygosity (0.12 +/- 0.08) and
      observed allelic diversity (1.5 +/- 0.04) as compared to both continental and
      island populations of B. terrestris. No significant differentiation was found
      among populations of B. terrestris from the European continent. In contrast,
      island populations were all significantly and most of them strongly
      differentiated from continental populations. B. terrestris mitochondrial DNA is
      characterized by a low nucleotide diversity: 0.18% +/- 0.07%, 0.20% +/- 0.04% and
      0.27% +/- 0.04% for the continental populations, the island populations and all
      populations together, respectively. The only haplotype found in the Tenerife
      population differs by a single nucleotide substitution from the most common
      continental haplotype of B. terrestris. This situation, identical to that of
      Tyrrhenian islands populations and quite different from that of B. lucorum (15
      substitutions between terrestris and lucorum mtDNA) casts doubts on the species
      status of B. canariensis. The large genetic distance between the Tenerife and B.
      terrestris populations estimated from microsatellite data result, most probably,
      from a severe bottleneck in the Canary island population. Microsatellite and
      mitochondrial DNA data call for the protection of the island populations of B.
      terrestris against importation of bumble bees of foreign origin which are used as
      crop pollinators.

PMID- 9147694
TI  - Limited polymorphism at major histocompatibility complex (MHC) loci in the
      Swedish moose A. alces.
AB  - The Swedish moose was analysed for genetic variability at major
      histocompatibility complex (MHC) class I and class II DQA, DQB and DRB loci using
      restriction fragment length polymorphism (RFLP) and single strand conformation
      polymorphism (SSCP) techniques. Both methods revealed limited amounts of
      polymorphism. Since the SSCP analysis concerned an expressed DRB gene it can be
      concluded that the level of functional MHC class II polymorphism, at least at the
      DRB locus, is low in Swedish moose. DNA fingerprinting was used to determine if
      the unusual pattern of low MHC variability could be explained by a low degree of
      genome-wide genetic diversity. Hybridizations with two minisatellite probes gave
      similarity indices somewhat higher than the average for other natural population,
      but the data suggest that the low MHC variability cannot be explained by a recent
      population bottleneck. However, since minisatellite sequences evolve more rapidly
      than MHC sequences, the low levels of MHC diversity may be attributed to a
      bottleneck of more ancient origin. The selection pressure for MHC variability in
      moose may also be reduced and we discuss the possibility that its solitary life
      style may reduce lateral transmission of pathogens in the population.

PMID- 9147695
TI  - The phylogeographic pattern of mitochondrial DNA variation in the Dall's porpoise
      Phocoenoides dalli.
AB  - We used 11 restriction endonucleases to study mtDNA variation in 101 Dall's
      porpoises Phocoenoides dalli from the Bering Sea and western North Pacific. There
      was little phylogeographic patterning among the 34 mtDNA haplotypes identified in
      this analysis, suggesting a strong historical connection among populations across
      this region. Nonetheless, mtDNA variation does not appear to be randomly
      distributed in this species. Both GST and AMOVA uncovered significant differences
      in the distribution of mtDNA variation between the Bering Sea and western North
      Pacific populations. These mtDNA results, coupled with differences in allozyme
      variation and parasite infestation, support the demographic distinctiveness of
      Bering Sea and western North Pacific stocks of Dall's porpoise. The lack of a
      strong phylogeographic orientation of mtDNA haplotypes within the Dall's porpoise
      is similar to the pattern reported in other vertebrates such as coyotes,
      blackbirds, chickadees, marine catfish, and catadromous eels. Like Dall's
      porpoise, these species are broadly distributed, and have large populations
      linked by moderate to high levels of gene flow. However, the more complex, deeply
      branched phylogenetic network of mtDNA haplotypes within Dall's porpoise,
      relative to these other vertebrates, suggests important differences between these
      species in the forces shaping mtDNA variation. One such force is the effective
      size of female populations, which appears to have been comparatively large and
      stable in Dall's porpoise.

PMID- 9147696
TI  - Microsatellite differentiation between Phillip Island and mainland Australian
      populations of the red fox Vulpes vulpes.
AB  - Predation by the red fox Vulpes vulpes is believed to be threatening the little
      penguin Eudyptula minor on Phillip Island in Victoria. Polymorphism at seven
      microsatellite loci was examined to estimate the extent of differentiation
      between Phillip Island and mainland populations of V. vulpes. Loss of alleles has
      occurred on Phillip Island where foxes first appeared approximately 88 years ago
      compared with mainland populations. Genetic differentiation between the Phillip
      Island and mainland populations was high. The relatively high differentiation
      found between the two populations could be due to either low migration rates, the
      effect of the composition of founder animals or both effects. Further ecological
      and historical information about the populations is needed to explore the likely
      significance of these effects.

PMID- 9147698
TI  - Electrocardiographic and electrophysiologic characterization of atypical atrial
      flutter in man: use of activation and entrainment mapping and implications for
      catheter ablation.
AB  - INTRODUCTION: Although the circuit in typical counterclockwise atrial flutter has
      been clearly delineated, the mechanisms of "atypical atrial flutters" have been
      less well characterized. The purpose of this study was to investigate the ECG and
      electrophysiologic (EP) characteristics of atypical atrial flutter. METHODS AND
      RESULTS: Thirty-three patients with at least one form of atypical atrial flutter
      underwent EP evaluation with multipolar atrial activation and entrainment
      mapping. Nineteen patients with clockwise flutter had: (1) stereotypic ECG
      morphology; (2) same cycle length as counterclockwise flutter; (3) clockwise
      activation around the tricuspid annulus; (4) recording of discrete split
      potentials along the length of the crista terminalis, suggesting the presence of
      conduction block; (5) concealed entrainment from the low right atrial isthmus;
      (6) successful ablation in this isthmus. Twenty patients with atypical flutter
      not consistent with a clockwise mechanism ("true atypical flutter") showed: (1)
      heterogeneous ECG morphology; (2) cycle length shorter than that of clockwise
      flutter; (3) frequent transitions from and to atrial fibrillation; (4) could be
      entrained in only six patients and, when accomplished, demonstrated surface
      fusion when entraining from the low right atrial isthmus. CONCLUSIONS: Atypical
      flutter falls into two broad categories. Clockwise flutter uses the same circuit
      with the same endocardial barriers as its counterclockwise counterpart and is
      best considered a form of typical flutter. True atypical flutter induced in the
      EP laboratory is a heterogeneous group of arrhythmias that are transitional to
      atrial fibrillation. Although it may superficially resemble clockwise or
      counterclockwise flutter based on the 12-lead ECG alone, the distinction can be
      readily made from a combined evaluation including activation and entrainment
      mapping.

PMID- 9147697
TI  - Detection and pattern of interspecific hybridization between Gliricida sepium and
      G. maculata in Meso-America revealed by PCR-based assays.
AB  - Gliricidia sepium provides a variety of products important for rural communities
      in tropical countries. Native populations in Meso-America currently form an
      important source of seed for distribution to farmers, but concerns centre on
      mechanisms which may lead to their genetic erosion, including anthropogenic
      dispersal and subsequent introgression from the related species, G. maculata.
      Populations of Gliricidia were examined genetically using approaches based on the
      polymerase chain reaction to test for interspecific hybridization and
      introgression between G. sepium and G. maculata. Analysis involved 13 RAPD and
      two RFLP-PCR markers which were identified to have species-diagnostic
      distributions. Data from both approaches corresponded and indicated three
      locations where multilocus genotypes were consistent with an hybrid origin. Data
      at one of these sites was consistent with introgression following hybridization.
      The hybrid origin of populations was supported by the intermediate geographical
      location of these sites to 'pure' populations of each species. Analysis of
      maternally inherited organellar DNA, which involved the detection of SSCPs in
      mitochondrial DNA amplification products, allowed further delineation of genetic
      structure among Gliricidia populations. Mitochondrial data indicated a high
      degree of organelle differentiation between sampled locations and identified G.
      sepium- and G. maculata-diagnostic haplotypes. This data supported the
      interpretation of genetic structure based on RAPDs and RFLP-PCR. In addition,
      cytonuclear analysis allowed the directionality of gene transfer during the
      formation of hybrid populations to be described. Despite evidence for the
      occurrence of interspecific hybridization and introgression in Gliricidia,
      important resource populations of G. sepium on the Pacific coast appear to have
      retained their genetic integrity. Implications in terms of the conservation and
      utilization of genetic resources within the genus are discussed.

PMID- 9147699
TI  - The zone of vulnerability to T wave shocks in humans.
AB  - INTRODUCTION: Shocks during the vulnerable period of the cardiac cycle induce
      ventricular fibrillation (VF) if their strength is above the VF threshold (VFT)
      and less than the upper limit of vulnerability (ULV). However, the range of shock
      strengths that constitutes the vulnerable zone and the corresponding range of
      coupling intervals have not been defined in humans. The ULV has been proposed as
      a measure of defibrillation because it correlates with the defibrillation
      threshold (DFT), but the optimal coupling interval for identifying it is unknown.
      METHODS AND RESULTS: We studied 14 patients at implants of transvenous
      cardioverter defibrillators. The DFT was defined as the weakest shock that
      defibrillated after 10 seconds of VF. The ULV was defined as the weakest shock
      that did not induce VF when given at 0, 20, and 40 msec before the peak of the T
      wave or 20 msec after the peak in ventricular paced rhythm at a cycle length of
      500 msec. The VFT was defined as the weakest shock that induced VF at any of the
      same four intervals. To identify the upper and lower boundaries of the vulnerable
      zone, we determined the shock strengths required to induce VF at all four
      intervals for weak shocks near the VFT and strong shocks near the ULV. The VFT
      was 72 +/- 42 V, and the ULV was 411 +/- V. In all patients, a shock strength of
      200 V exceeded the VFT and was less than the ULV. The coupling interval at the
      ULV was 19+/- 11 msec shorter than the coupling interval at the VFT (P < 0.001).
      The vulnerable zone showed a sharp peak at the ULV and a less distinct nadir at
      the VFT. A 20-msec error in the interval at which the ULV was measured could have
      resulted in underestimating it by a maximum of 95 +/- 31 V. The weakest shock
      that did not induce VF was greater for the shortest interval tested than for the
      longest interval at both the upper boundary (356 +/- 108 V vs 280 +/- 78 V; P <
      0.01) and lower boundary (136 +/- 68 msec vs 100 +/- 65 msec; P < 0.05).
      CONCLUSIONS: The human vulnerable zone is not symmetric with respect to a single
      coupling interval, but slants from the upper left to lower right. Small
      differences in the coupling interval at which the ULV is determined or use of the
      coupling interval at the VFT to determine the ULV may result in significant
      variations in its measured value. An efficient strategy for inducing VF would
      begin by delivering a 200-V shock at a coupling interval 10 msec before the peak
      of the T wave.

PMID- 9147701
TI  - Secretion of both IL-2 and IL-4 by tumor cells results in rejection and immunity.
AB  - The generation of a therapeutic immune response to malignancy is critically
      dependent on the inherent immunogenicity of the tumor. Our study demonstrates
      that secretion of both interleukin-2 (IL-2) and IL-4 by a seemingly
      nonimmunogenic tumor abrogates tumorigenicity, and mice that have rejected the
      genetically modified tumor are immune to challenges with the parental tumor. The
      induction of immunity by the IL-2/IL-4-secreting tumor was significantly better
      than that achieved with the admixture of tumor cells and the classic adjuvant,
      Corynebacterium parvum. To elicit a primary immune response, the majority of
      cells needed to secrete both cytokines. Ad-mixture of IL-2-secreting cells with
      IL-4-secreting cells did not result in tumor cell rejection. The IL-2/IL-4
      secreting tumor cells were efficiently rejected in animals immunosuppressed by
      total body irradiation. Depletion of CD4+ or CD8+ T cells did not abrogate
      rejection of the tumor cells, but the animals depleted of CD4 cells failed to
      generate protective immunity. Our study demonstrates that secretion of the
      combination of IL-2 and IL-4 significantly enhances tumor immunogenicity. The
      requirement of cells secreting both cytokines suggests an intricate mechanism
      different from the mere presence of both cytokines at the tumor-inoculation site.

PMID- 9147700
TI  - Induction of autologous tumor-specific cytotoxic T-lymphocyte activity against a
      human renal carcinoma cell line by B7-1 (CD8O) costimulation.
AB  - Recently mouse models have shown that expression of costimulatory molecules such
      as B7-1 on tumor cells can induce tumor-specific immunity, suggesting that tumor
      cells modified to express costimulatory molecules can be a potential tumor
      vaccine. To investigate the importance of B7-1 co-stimulation in induction of
      autologous tumor immunity in humans, we established a renal carcinoma cell line,
      RCC-1, from a tumor resection and studied the patient's antitumor immune
      responses in vitro. The RCC-1 cell line constitutively expressed major
      histocompatibility complex (MHC) class I, intercellular adhesion molecule (ICAM)
      1, and leukocyte function-associated antigen (LFA)-3 molecules, and MHC class II
      molecules were induced by interferon-gamma (IFN-gamma) treatment in vitro.
      However, neither RCC-1- nor IFN-gamma-treated RCC-1 cells expressed B7-1, and
      both failed to induce T-cell proliferative responses in mixed lymphocyte and
      tumor cell reaction (MLTR) assays, suggesting that the costimulatory signals
      provided by cell adhesion molecules such as ICAM-1 and LFA-3 were not sufficient
      to elicit an antitumor immune response. However, on transfection of the human B7
      1 into RCC-1, these cells were able to induce a significant T-cell proliferation
      in MLTR assays. This T-cell response could be blocked by anti-B7 mAb treatment of
      the tumor cells. RCC-1B7 cells also induced the generation of tumor-specific
      cytolytic T lymphocytes to the parent RCC-1 cells in vitro, with little
      nonspecific cytolysis of an unrelated RCC line, A498, or autologous
      phytohemagglutinin (PHA) blasts. This specific cytotoxicity could be abrogated by
      anti-CD8 mAb and complement treatment. In summary, our study indicates that B7-1
      CD28 interaction plays a critical role in induction of autologous tumor-specific
      cytotoxic T lymphocytes (CTLs) in humans, suggesting that the costimulatory
      molecule transfected tumor cells could be useful in expanding tumor-specific
      autologous CTL in vitro for adoptive tumor immunotherapy.

PMID- 9147702
TI  - Murine cells transfected with human Hsp27 cDNA resist TNF-induced cytotoxicity.
AB  - Hyperthermia sensitizes tumor cells to killing by tumor necrosis factor-alpha
      (TNF). Sensitization is greater in cells exposed to TNF before heating begins
      than with the reverse sequence, and heat-shock proteins (hsp) have been suggested
      to protect cells from TNF cytotoxicity. Here we examined the role of Hsp27 in TNF
      resistance. Murine L929 cells were stably transfected with the vector pRc/CMV
      constitutively to express an inserted human hsp27 complementary DNA (cDNA)
      sequence. Parental cells produced no detectable murine homolog to human hsp27.
      Hsp27-sense clones expressed hsp27 messenger RNA (mRNA) and protein at 37 degrees
      C. Cells transfected with the cDNA in the anti-sense orientation produced anti
      sense mRNA but no protein, and cells transfected with the vector alone produced
      neither product. Expression of hsp27 conferred significant resistance to TNF
      cytotoxicity in both neutral red cytotoxicity and clonogenic survival assays.
      Vector along and hsp27 anti-sense transfectants had a TNF response similar to
      that of parental L929 cells. Kinetic studies in L929 cells showed that hsp27
      expressing clones exhibited resistance relative to parental cells beginning 6 h
      after TNF exposure, and this differential response increased by 12 and 24 h.
      Addition of actinomycin D to the TNF cytotoxicity assays accelerated the
      cytotoxicity development in parental and transfected cells, but the hsp27-sense
      clones were still more resistant. Hsp27-sense clones of L929 cells were also
      resistant to oxidative stress induced by menadione and released less arachidonic
      acid in response to TNF induction. These results show that hsp27 can negatively
      regulate the TNF cytotoxic mechanism.

PMID- 9147703
TI  - [Phlebotomines of Nicaragua. II. Description of Lutzomyia legerae n. sp.
      (Diptera:Psychodidae)].
AB  - Both sexes of Lutzomyia legerae n. sp., a new species of phlebotomine sand fly
      belonging to the subgenus Lutzomyia, cruciata complex, are described from
      specimens collected in peridomestic environment, by light-trap, in central
      Nicaragua. Females of the new species are very close to L. cruciata. Therefore,
      in the leishmaniasis foci where the two species occur sympatrically implication
      of each species as a vector has to be carefully investigated.

PMID- 9147704
TI  - [A probable case of human subconjunctival dirofilariasis observed by Amatus
      Lusitanus in the south of France in the 16th century].

PMID- 9147705
TI  - [The phlebotomines of Lebanon. I. Results of preliminary collections (August,
      1994)].

PMID- 9147706
TI  - Phase III trials: specific problems associated with the use of a placebo control
      group.
AB  - The topic of placebos in clinical research has been recently addressed in general
      journals and is relevant to a clinical pharmacologists' readership as well. We
      try to give an overview of benefits as well as problems of this methodology.
      Although the use of placebo in drug development is frequently absolutely
      essential, important ethical and technical problems are generally involved. The
      placebo-controlled trial, although methodologically pure, may sometimes cause too
      much difficulties in the clinical setting.

PMID- 9147707
TI  - Once-daily fixed dose combinations of verapamil and trandolapril in black
      patients with mild to moderate hypertension: a new choice for first line
      treatment.
AB  - Using ambulatory blood pressure (BP) monitoring, a potent ACE-inhibitor/calcium
      channel blocker combination was tested in 21 Black patients (age 52 +/- 10 years;
      10 males, 11 females) with mild to moderate hypertension (mean 12-hour daytime
      diastolic BP > or = 90 mmHg and < or = 114 mmHg). After a 14-day wash-out and a
      14-day placebo run-in period, therapy was initiated with verapamil 180 mg plus
      trandolapril 2 mg. At monthly visits, if mean daytime diastolic BP remained > or
      = 90 mmHg, the dose combination was uptitrated stepwise to verapamil 240 mg plus
      trandolapril 4 mg, verapamil 360 mg plus trandolapril 4 mg, and finally
      hydrochlorothiazide 12.5 mg were added. Mean 24-hour BP dropped from 150 +/-
      14/96 +/- 7 mmHg at baseline to 131 +/- 13/82 +/- 8 mmHg after 4 months treatment
      (p < 0.001). In 16 (76%) patients mean 24-hour diastolic BP was < 90 mmHg at the
      end of the trial and 15 (71%) patients achieved a reduction of > 10 mmHg. Five
      out of 5 patients finishing on dose I were controlled, 5/6 patients on dose II,
      5/8 patients on dose III, and 1/2 patients who received additional
      hydrochlorothiazide. The 24-hour BP load fell from 72 +/- 8% at baseline to 35 +/
      25% in 4 months (p < 0.001). Mean diastolic BP drop for the 2 peak hours during
      daytime was 20 mmHg and for the last 2 hours of monitoring was 13 mmHg, resulting
      in a trough to peak ratio of 65%. There were no significant adverse events or
      biochemical abnormalities. It is concluded that the combination doses tested
      showed a sustained and marked antihypertensive effect throughout the 24-hour
      dosing interval, and the starting dose (verapamil 180 mg plus trandolapril 2 mg)
      seems appropriate in this group of patients.

PMID- 9147708
TI  - Thromboxane A2 does not mediate angiotensin II-dependent nonischemic peripheral
      vasoconstriction in healthy men: a pilot study.
AB  - It has been suggested that angiotensin II-dependent hemodynamic effects are in
      part mediated by thromboxane A2 (TXA2). The present study investigates in 6
      healthy normotensive men whether prostaglandin H2-TXA2 receptor blockade with 100
      mg of linotroban (5(2-(phenylsulfonylamino)ethyl)-thienyloxy-acetic acid) p.o.
      influences angiotensin II-dependent peripheral regional vasoconstriction.
      Moreover, the regional balance of thromboxane B2 (TXB2), a stable metabolite of
      TXA2, across the leg vascular bed was assessed at baseline conditions as well as
      during exogenous infusion (0.2 microgram/min) of angiotensin II. Net transfemoral
      TXB2 balance was calculated from the respective arteriovenous plasma
      concentration differences and the corresponding regional plasma flow, the latter
      being determined by indocyanine-green dye, using appropriate catheterization
      techniques. Angiotensin II (0.2 microgram/min) induced a 66% increase in leg
      vascular resistance (p < 0.01) without affecting systemic hemodynamics. These
      regional hemodynamic effects of angiotensin II were not influenced by
      prostaglandin H2-TXA2 receptor blockade. Baseline TXB2 balance across the femoral
      vascular bed was equilibrated at slight extraction rates or around zero and
      remained unchanged during angiotensin II infusion. These results suggest that, in
      healthy man, angiotensin II-dependent, nonischemic peripheral vasoconstriction is
      not mediated by TXA2. Possible benefits of prostaglandin H2-TXA2 receptor
      blockade in pathological conditions with tissue malperfusion or ischemia are
      discussed.

PMID- 9147709
TI  - Comparative study of acipimox and pravastatin in patients with combined
      hyperlipidemia.
AB  - The aim of this study was to evaluate the lipid-lowering effect of acipimox as
      compared to pravastatin in patients with combined hyperlipidemia. One hundred and
      six subjects, all males, aged 18-60 years, with total cholesterol (TC) > or = 200
      mg/dl, TC/HDL-C ratio > or = 5, triglycerides (TG) > or = 200 and > or = 350
      mg/dl were randomized to receive acipimox 250 mg thrice daily or pravastatin 20
      mg once daily for 3 months, according to a double-blind, double-dummy design.
      After a 1-month wash-out period patients were crossed to the alternative regimen
      for further 3 months. Prior to and at the end of each treatment period, TC, LDL
      C, HDL-C, TG, blood glucose, and fibrinogen were evaluated. Both acipimox and
      pravastatin significantly decreased TC, LDL-C, TC/HDL-C ratio and TG and
      increased HDL-C, without affecting plasma glucose. However, at the dosages
      employed in the study acipimox was more effective in reducing TG and increasing
      HDL-C levels, whereas pravastatin was more efficient in decreasing TC and LDL-C.
      There was no difference between the 2 treatments in their effects on TC/HDL-C
      ratio. Unlike pravastatin acipimox caused a slight but significant reduction in
      fibrinogen plasma levels. No serious adverse event was observed with either drug,
      but a major incidence of side-effects was reported during treatment with
      acipimox. Our findings suggest that, although both drugs at the standard dose
      employed in the study were effective in improving the lipid profile; in the
      treatment of combined hyperlipidemia acipimox might be preferable in the presence
      of more pronounced hypertriglyceridemia with low levels of HDL-C, whereas
      pravastatin might be more useful when hypercholesterolemia is predominant.

PMID- 9147710
TI  - Food interaction study of a new theophylline (Egifilin) 200 and 400 mg retard
      tablet in healthy volunteers.
AB  - The aim of the present food interaction study was to determine the blood plasma
      levels of theophylline upon the administration of new Egifilin 200 and 400 mg
      retard tablets, either on an empty stomach or after meal, and to make comparative
      pharmacokinetic evaluation in 26 healthy volunteers. For determination of the
      plasma levels of theophylline an improved isocratic HPLC-UV method was used in
      the concentration range of 0.1-18 micrograms/ml. The mean pharmacokinetic curves
      obtained with 200 and 400 mg tablets before and after meal were in good agreement
      also on the basis of statistical evaluation, although, as usual with
      theophylline, the evaluation of the individual pharmacokinetic curves indicated
      great variations. The pharmacokinetic parameters (AUCzero-t, AUCzero-infinity,
      HVD, MRT, Cmax, tmax) calculated for Egifilin 200 and 400 mg retard tablets were
      analyzed by ANOVA, ANOVAlog, Wilcoxon, and Schuirmann statistical tests as well
      as by the confidence interval calculation. As it was found, under the
      circumstances of the present food interaction study, food consumption did not
      have a biologically significant effect on the pharmacokinetic parameters of
      either the 200 or the 400 mg Egifilin retard preparations.

PMID- 9147711
TI  - Dose-dependency of oxazaphosphorine pharmacokinetics.

PMID- 9147712
TI  - Disposition of mitomycin C after local intraarterial application.

PMID- 9147714
TI  - Conditions of drug delivery within solid tumors, and noninvasive methods for
      studies in humans.

PMID- 9147713
TI  - Dosage individualization of carboplatin and etoposide based on pharmacokinetic
      investigations.

PMID- 9147715
TI  - Idarubicin: a brief overview on pharmacology and clinical use.
AB  - Idarubicin exhibits features rendering this drug unique among anthracyclines. The
      higher lipophilicity leads to faster accumulation in the nuclei, superior DNA
      binding capacity and consequently greater cytotoxicity compared to daunorubicin.
      A major advantage over this reference drug is its ability to overcome MDR at
      least partially. Its major metabolite idarubicinol is as active as the parent
      compound and crosses the blood-brain barrier. Furthermore, idarubicin can be
      administered orally reaching sufficient plasma levels. Compared to other
      anthracyclines, the risk of cardiotoxicity as the main side effect for this group
      of drugs is reduced with idarubicin, when administered in a therapeutical dose.
      Thus, IDA has become an important drug in the treatment of acute leukemias and
      its potency in lymphomas, plasmocytomas and other solid tumors such as breast
      cancer is currently under investigation in several clinical studies.

PMID- 9147716
TI  - Pharmacokinetic interactions of antineoplastic agents.

PMID- 9147717
TI  - Cancer therapy with liposomal formulations of anticancer drugs.

PMID- 9147718
TI  - Abdominal aortic aneurysm presenting as meralgia paraesthetica.
AB  - A case of abdominal aortic aneurysm is reported in a patient with long standing
      low back pain, presenting as meralgia paraesthetica and an increase in the
      severity of back pain. The case highlights the need for objective assessment of
      new symptoms arising in a chronic condition, and for a systematic approach to the
      assessment of radiographs performed in the accident and emergency department.

PMID- 9147719
TI  - Managing the managers.

PMID- 9147720
TI  - The development of a Bacillus subtilis 168 culture condition for enhanced and
      accelerated beta-mannanase production.
AB  - A shaken flask cultivation condition for enhanced and accelerated beta-mannanase
      formation by Bacillus subtilis 168 was achieved. Among five examined fermentation
      media a formula that supported enzyme generation and retarded biomass yield and
      sporulation was selected. The deficiency of biomass production in this medium was
      mastered by choosing a seed culture medium that accelerated growth and initiation
      of beta-mannanase synthesis. With respect to enzyme production, the optimum pH
      and temperature were 7 and 37 degrees C, respectively. The biosynthesis of the
      enzyme was extremely influenced by the cell growth state as a modulator, glucose
      as a catabolite repressor, and galactomannan as an inducer. A galactomannan
      concentration of 4 g l-1 induced a beta-mannanase activity level of 17.5 U ml-1
      after 24 h of incubation at the experimental condition. Higher inducer
      concentrations supported growth rather than enzyme production. The influence of
      inoculum size was so remarkable that, at optimum, a crude filtrate with an enzyme
      activity of 33U ml-1 was yielded within 4 hours. It appears that this is among
      the highest rates reported for beta-mannanase production. We have also
      demonstrated that blocking of the sporulation process at stage II do not affect
      enzyme production significantly. This would allow an extended enzyme production
      phase especially in a continuous culture.

PMID- 9147721
TI  - Incidence of wound infection in three different departments and the antibiotic
      sensitivity pattern of the isolates in a Saudi Arabian hospital.
AB  - The incidence of wound infection in three different departments: general surgery
      (GS), interdisciplinary intensive care (IIC) and pediatric intensive care (PIC)
      in King Khalid Hospital in Hail was studied during the hot months June-October. A
      total of 2,331 wounds were examined. One hundred and ninety-three of them were
      infected (8%). The overall monthly infection rates in these departments were
      significantly different. They were 18, 9 and 4% in the IIC, GS, and PIC
      respectively. The monthly infection rates varied, the highest rates occurred in
      July. Two hundred and eighty three strains were isolated from the infected
      wounds. Seventy ones were isolated during June, and 69, 60, 42 and 41 strains
      were isolated during July, October, August and September, respectively- Thirty
      five per cent of these strains were identified as Staphylococcus aureus, 31% as
      Escherichia coli, 25% as Pseudomonas aeruginosa, and 10% as Klebsiella. S. aureus
      was the predominant organism during July; while E. coli predominated during
      August and October. S. aureus and P. aeruginosa strains were isolated in equal
      numbers during June. The sensitivity of these bacteria to ampicillin, cephalotin,
      cefotaxime, cefoxitin, tetracycline, chloramphenicol and gentamicin was tested by
      the standard disk diffusion technique. The most effective antibiotic against S.
      aureus was chloramphenicol (78%) followed by gentamicin (63%) and tetracycline
      (57%); against E. coli cefotaxime (82%) followed by cefoxitin (77%), cephalitin
      (62%) and chloramphenicol (53%); against Klebsiella cefotaxime (95%) followed by
      chloramphenicol (90%), tetracycline (70%), cephalotin and gentamicin (each 66%);
      and cefoxitin (60%); against P. aeruginosa cefotaxime (56%), gentamicin (33%) and
      chloramphenicol (29%).

PMID- 9147722
TI  - In vivo studies on Aujeszky's disease virus mutants.
AB  - We report the construction and in vivo analysis of three recombinant Aujeszky's
      disease virus (ADV) strains containing mutations at three different loci of the
      genome. Mutant vE16lac was generated by deleting of 2976 bp DNA fragment which
      covers 1851 bp of the right arm of UL component, the UL-US junction, the "a"
      element of the internal repeat (IR) region and a putative LAT promoter. Mutant
      vRRlac was generated by deletion of a 1805 bp fragment from the coding region of
      the large and small subunits of ribonucleotide reductase gene (rr). The third
      mutant, vTKlac, was constructed using insertional mutagenesis of the thymidine
      kinase gene (tk). In the constructed mutants a lacZ gene expression cassette was
      either inserted into the target gene (vTKlac) or replaced the deleted DNA segment
      (vE16lac, vRRlac). Constructed recombinant viruses were analyzed by infecting
      pigs and monitoring the virus excretion from nasal fluid and disease symptoms.
      Tissue specimens were collected for virus isolation and pathological examination.
      Strains vTKlac and vRRlac retained the ability to establish an infection, but
      showed reduced replication efficiency in the respiratory tract and were unable to
      attack the central nervous system (CNS) of pigs. Thus, both deletions induce
      significant attenuation of the virus measured by decrease of virulence in
      infected pigs. Strain vE16lac showed disease symptoms similar to that of wild
      type and could be detected in the CNS of pigs.

PMID- 9147723
TI  - The problems of food-borne disease in Hungary.

PMID- 9147724
TI  - The species composition of oligotrophic bacterial communities of Lake Balaton--a
      numerical analysis.
AB  - From among the 565 aerobic and facultatively anaerobic, oligotrophic bacterial
      isolated obtained from the open water region of the Balatonfured-bay, 58
      representative strains were selected for detailed taxonomic-physiological studies
      and numerical analyses as well as simultaneous comparisons with authentic
      bacterial strains isolated earlier by Lango (1987) from different water habitat
      of the Lake Balaton. On the basis of 186 ceded differential diagnostic
      characteristics involved in these analyses and comparisons, the representative
      strains were classified into 6 larger similarity groups (I. Micrococcus spp.; II.
      Arthrobacter "globiformis"; III. Acinetobacter calcoaceticus; IV. Pseudomonas
      spp. I; V. Pseudomonas spp. II; VI. Aeromonas spp.) which were partly further
      divided into smaller subgroups of species level (IV.a. Pseudomonas palleronii;
      V.a. Pseudomonas pseudoalcaligenes; V.b. Pseudomonas acidovorans; V.c.
      Pseudomonas fluorescens; VI.a. Aeromonas caviae; VI.b. Aeromonas hydrophila).

PMID- 9147725
TI  - Detection of bullous pemphigoid antibodies by means of synthetic peptides as
      antigenic epitopes.
AB  - In an earlier study, the circulating autoantibodies in patients with bullous
      pemphigoid (BP) were demonstrated in higher frequencies by means of an immunoblot
      technique then via indirect immunofluorescence. In the present work with the help
      of Peptide Structure software, two matched antigenic epitopes were chosen and
      synthesized. The sera of 34 patients with BP were investigated in parallel by an
      immunoblot technique using a human epidermal extract, and by an ELISA technique
      with synthetic peptides. The sera of 16 healthy persons and 10 patients with
      other bullous diseases served as controls. Among the 34 patients with BP, 23 sera
      proved positive for at least one synthetic peptide. Positive reactions with the
      major BP antigen (230 kD) were found in 22 patients by immunoblot technique and
      in 16 patients by the ELISA technique with the synthetic peptide, whereas with
      the minor BP antigen (180 kD), positive reactions were found in 9 patients by the
      immunoblot technique and 18 patients by the ELISA technique using the synthetic
      antigenic epitope of the minor BP antigen. All control sera were negative for
      both antigens in ELISA investigations. In 3 patients with pemphigus vulgaris,
      characteristic bands against pemphigus vulgaris antigen were identified by means
      of the immunoblot technique, but all other cases were negative. It is suggested
      that the development of this technique may lead to an opportunity for the rapid
      and simple diagnosis of BP.

PMID- 9147726
TI  - Large scale cultivation of an anti-D (IgM) antibody producing human/mouse
      heterohybridoma.
AB  - A human/mouse heterohybridoma cell line secreting anti-Rh(D) antibody was
      established by the fusion of Epstein-Barr Virus (EBV) transformed human B
      lymphocytes and human/mouse heteromyelomas. During scaling-up the cell line was
      adapted to suspension culture, then medium composition was gradually altered into
      a more economical one. The adapted cell line has kept its multiplication and
      antibody secreting characteristics in the new medium. Parameters of large scale
      batch cultivation in bioreactors were optimized in working volume of 3.6 litre
      and production was carried out under these parameters in working volume of 24
      litre. Optimized parameters were the follows: (i) the cell line is highly
      sensitive to dissolved oxygen (DO) level, its optimal DO is 10%; (ii) optimal
      inoculum cell count is 3 x 10(5) cell/ml; (iii) Marine-blade impeller was chosen
      for supporting the requested oxygen transfer. Using the optimized parameters
      HUMAN Co. Ltd. produces the Monoclonal Anti-D (IgM) reagent, which has been
      registered in 1995 in Hungary and now it is on the market.

PMID- 9147727
TI  - Effect of medium composition on hybridoma growth and antibody production.
AB  - Two murine hybridoma cell lines named 1D12 and 3B1 secreting antibody against
      human blood group B were developed. Effect of medium composition and hyperosmotic
      stress on cell growth, viability and monoclonal antibody (MAb) production was
      examined during down-stream process in suspension culture. Both of the cell lines
      secreted MAb of higher titre if the basal medium was supplemented with 2.5 g/l L
      glucose and 419 mg/l L-glutamine. Additional nutrients like transferrine, amino
      acids, ethanolamine, selenium were added to promote cell growth and viability. In
      case of cell line 1D12 enhancement of MAb production was observed using hyper
      osmotic medium as well. Having data of these preliminary experiments we optimized
      the large scale production of MAbs in bioreactor. These MAbs serve as a base of
      the anti-B blood group reagent registered in Hungary.

PMID- 9147728
TI  - Effect of microwaves on survival of some bacterial strains.
AB  - While the inhibitory effect of microwave radiation on microorganisms is being
      researched intensively, how microwave radiation brings about this effect has been
      a matter of discussion. Some researchers support that this effect is of a thermal
      character, whereas some others maintain a non-thermal effect. In this work, 1 ml
      suspensions of Pseudomonas aeruginosa, Pseudomonas acidovorans staphylococcus
      aureus and Staphylococcus epidermidis bacteria were subjected to microwave
      radiation at 2450 MHz and 550 Watts for periods of 5, 6, 7, 8, 10, 12, 14, 16,
      18, 20, 25 and 30 seconds. When each result was compared with the CFU/ml results
      obtained from unradiated control group bacterial suspensions derived from stock
      cultures, significant conclusions were attained (P < 0.001). The same experiments
      were repeated with the application of conventional heating. The difference
      between the CFU/ml values of similar bacterial suspensions subjected to microwave
      radiation and conventional heating was significant (P < 0.001). Concurrently, the
      fact that the effect was exacerbated upon increasing of liquid volume during the
      application of microwave radiation was established via the results obtained
      through the application of microwave radiation to 1 ml and 5 ml bacterial
      suspensions (P < 0.001).

PMID- 9147729
TI  - The effect of trace elements on the immune response of rats with intact or
      injured immune system.
AB  - We studied the effect of a trace element combination (Beres Drop Plus; BDP) on
      the immune response of rats, with intact and with injured immune system. Rats
      were treated with different doses of BDP for 26 days. The immune system was
      injured by 7.0 Gy whole body gamma irradiation on the first day of BDP treatment.
      Rats were immunized on the 31st day of the BDP treatment with sheep red blood
      cells. In the spleen the cell count and the number of antibody producing cells
      were determined. In the serum the titre of hemolysin was tested. In rats with
      intact immune system all used doses of BDP induced elevation of the immune
      response. The moderate high doses were especially effective. In rats with injured
      immune system the effect was less. Only the 250 microliters/kg body weight dose
      could elevate the immune response, and the highest (500 microliters/kg) dose
      reduced the response.

PMID- 9147731
TI  - Bibliography. Current world literature. Theory and simulation.

PMID- 9147730
TI  - Human herpesvirus 8 in classic Kaposi sarcoma.
AB  - Recent studies suggest the role of a new human herpesvirus (HHV8) in the
      pathogenesis of different forms of Kaposi sarcoma (KS). In the present work we
      investigated the presence of HHV8 sequences in KS tumour tissues from patient
      with classic KS. Since clear evidences point to the role of immune suppression in
      the development of AIDS-associated KS or patients receiving immunosuppressive
      therapy, immunological investigations were also performed. We could show a highly
      consequent association of HHV8 sequences with classic KS in the large series of
      patients supporting our previous findings that this virus might be in some way
      involved in the pathogenesis of this tumour. In addition immunological
      examination of the patients revealed a mild decrease in the CD4 positive cell
      number, a significantly reduced CD4/CD8 ratio, a diminished PHA reactivity and
      leukocyte migration factor production of lymphocytes. The changes observed in the
      present study are similar, but much less pronounced than those may be observed in
      HIV infection.

PMID- 9147732
TI  - Bibliography. Current world literature. Macromolecular assemblages.

PMID- 9147734
TI  - [Multicenter transverse study of the neurological ambulatory care in the Spanish
      Health System in Aragon: overall results].
AB  - OBJECTIVE: To evaluate clinical, diagnostic and therapeutic aspects and how the
      Neurology Outpatient Departments of Aragon work in practice. MATERIAL AND
      METHODS: For three consecutive months all patients attending the Neurology
      Outpatient Departments of the Health Areas of the Health Service of Aragon for
      the first time were given a specially designed questionnaire. RESULTS: The
      majority of the patients were women (57%). The average age was 51.5 +/- 20.6
      years. The family doctor referred 79.5% of the patients. The average waiting time
      for patients to be seen was 12.4 +/- 10.7 days. Further investigations were
      requested in 48.9% of the patients (cerebral CT in 18.1%, MR in 2.6%, EEG in 12%
      and ENG-EMG in 6.8%). The commonest diagnoses were headache (25.5%),
      cerebrovascular pathology (12.5%), extrapyramidal pathology (7.5%), syncope
      (6.5%), convulsions (6%), vertigo (5.9%), psychiatric disorders (5%), non
      neurological disorders (4.4%). No treatment was given to 15.64% of the patients
      attending for the first time. The commonest drugs used were: calcium antagonists
      (32.5%), platelet antiaggregants (20.9%), antidepressives (17%), antiepileptic
      drugs (15.6%) and NSAIDS (5.3%). CONCLUSIONS: There is a considerable demand for
      neurological consultations and there are few neurologists in proportion to the
      population. Better selection of the patients sent for consultation and a better
      understanding by family doctors of the commoner neurological disorders would
      considerably reduce the number of patients sent to the Outpatient Department.

PMID- 9147735
TI  - [Conners' rating scales in the assessment of attention deficit disorder with
      hyperactivity (ADHD). A new validation and factor analysis in Spanish children].
AB  - The use of Conner's Rating Scales (CRS) is very extended for the assessment of
      attention deficit disorder with hyperactivity (ADD-H). The main objective of this
      work is to study the validity of construct of CRS from theoretical basis and data
      statistical analysis. The study is based on a control group of 633 children and a
      clinical group of 33 subjects. We used a Spanish version of the Conner's Teacher
      Rating Scale (CTRS) and Conner's Parents Rating Scale (CPRS) in both groups. From
      the analysis of scales contents we attribute the items to several behavioral
      areas and we performed a factorial analysis. Studies of reliability, external
      validity versus clinical criteria, and analysis of correlations between parents
      and teachers scales were also performed. Findings from factorial analysis and
      study of reliability have shown the questions of CTRS to be clustered in three
      well-defined and reliable factors: hyperactivity, attention deficit, and conduct
      disorder. The questions dealing with emotional disorders are not sufficiently
      consistent to constitute a separate factor. CPRS has a lower reliability than
      CTRS, and its factorial analysis does not allow to consider a factorial
      distribution. The validity is high in CTRS and no significative in CPRS.
      Correlation between scales is also low. As a consequence of these results we
      propose a Spanish experimental revised form of the CTRS, with 20 items. This new
      form can assess separately: attention deficit; hyperactivity and conduct
      disorder, according to the current clinical criteria of CIE-10 and DSM-IV.

PMID- 9147733
TI  - [Clinical workload at the outpatient neuropediatric clinic].
AB  - OBJECTIVE: To obtain rapidly the basic clinical information from individual
      patients and about the total practice in a hospital based neuropediatric out
      patient clinic. MATERIAL AND METHODS: A database file was designed, performed by
      the medical staff during or immediately after the patients visit. A descriptive
      study of data obtained through 1995 is reported. RESULTS: 1,226 patients visited
      the clinic during the whole year, generating 2,315 visits. The percentage of new
      patients is larger than that of other pediatric specialties, except for pediatric
      cardiology, but it is similar to that reported by adult neurological patients.
      Age distribution show a bimodal curve with a peak during the first year of age
      and a second one at 11 years. Geographic distribution is similar to that of other
      outpatient clinics of our center. The most frequent motive, annually, to consult
      was headache followed by suspected epilepsy. The most frequent diagnoses in new
      patients were epilepsy, migraine and tension type headaches. Prevalence of
      diagnosis in the total number of patients visited showed the highest frequency of
      epilepsy, followed by mental retardation and cerebral palsy. EEG was study most
      often performed, and 46% of total number of patients had neuroimaging studies.
      The pharmacological agent used in the largest number of patients was sodium
      valproate while phenobarbital was the product most often discontinued. Non
      antiepileptic drugs were used in a comparative small number of cases. The
      percentage of patients discharged for chronic and severe diseases was 20%
      annually, while it amounted to 40% in new patients. CONCLUSIONS: This type of
      information allows doctors to plan resources needed at the clinic and by the
      patients, but it is not appropriate for other tasks belonging to the management
      area, since it would require a larger infrastructure than the one usually
      provided at the outpatient clinic.

PMID- 9147736
TI  - [Memory disorders in epileptic patients. A study of pre-postsurgical follow-up].
AB  - In general terms, epileptic patients with temporal lobe epilepsy (TLE) show
      mnesic deficits. In the case of medically intractable epilepsy (around 20%) the
      neurosurgery intervention is a widely accepted treatment. The cognitive effects
      of surgery have been reported in last years; they emphasize the mnesic positive
      changes of contralateral area. In the same sense they have reported a negative
      change on mnesic modality in ipsilateral area. This paper present a study in
      which the mnesic deficits of twenty eight pharmaco resistant epileptic patients
      have been evaluated and followed up. These patients have been submittes to a
      surgical treatment at the Epilepsy Surgical Unit of the Hospital de La Princesa
      (Madrid). The assessment pre and postoperative tested six months apart. The most
      common cognitive deficit affect bimodally to mnesic functions: so in the verbal
      as in the visospatial modality. This deficit correlated with the years epilepsy.
      Meanwhile, the following up study indicates that a relevant numbers of these
      patients show an improvement in the function of the contralateral hemisphere with
      respect to the area surgically treated. This finding probably is the consequence
      of seizure free.

PMID- 9147737
TI  - [Diagnostic difficulties in the narcolepsy-catalepsy syndrome: with reference to
      our series of cases].
AB  - The narcolepsy-cataplexy syndrome is a disorder of unknown aetiology,
      characterized by excessive daytime sleepiness associated with cataplexy and other
      REM sleep phenomena. Diagnosis is based on the clinical findings, although this
      may be difficult especially with respect to confirming the cataplexy. Objective
      tests, such as typing for HLA, DR2DQ1 (DRw15DQw6, WHO90) and above all TMLS
      (average latency < 5 mn and two or more onsets of sleep in the phases REM and
      SOREMP's) is of great help. However, the exact diagnostic significance of some
      aspects of these tests and their parameters is still under discussion. In this
      paper we review our series of cases consisting of fourteen patients who fulfil
      the clinical diagnostic criteria required in the ICSD-1990. TMLS and HLA typing
      was done for all. Of the HLA types, DQ1 was present in all our patients, unlike
      DR2 which was not found in two patients. Regarding TMLS, the average latency < 5
      mn is a parameter met by all cases, although one did not have SOREMP's. The
      findings of the objective tests done on our patients are in agreement with those
      described by other authors. They underline the significance of the support they
      lend to the diagnosis. However, they are not the definite answer to the problem.

PMID- 9147738
TI  - [The Ohtahara's syndrome: a special form of age-dependent epilepsy].
AB  - The aim of this report is to review the clinical and the outcome data in four
      patients with Ohtahara syndrome at Sant Joan de Deu Hospital, Barcelona,
      following the same clinical and electroencephalografic criteria reported by the
      author. The etiology of this syndrome is unknown and plurifactorial.
      Investigation studies were negative except for the EEG and neuroimaging. MRI was
      performed in two children, and pachigyria was observed in one and mycropoligyria
      in the other. There were no response to cofactors, phenobarbital, vigabatrine and
      valproate. Therefore two patients underwent treatment with ACTH with no response
      in one and good response in the other. Two patients died at 2 and 6 months; other
      one was transferred to another center at 6 months-old and was lost at follow-up.
      The fourth patient, fourteen-month-old, is free of seizures with improvement of
      EEG register with important development retardation. We conclude that Ohtahara
      syndrome is a severe neonatal epilepsy with poor neurologic outcome; MRI detects
      often brain malformations as cortical dysplasia and a therapeutic trial of ACTH
      is indicated because the possibility of control of the seizures.

PMID- 9147740
TI  - [Don Juan Jose Barcia Goyanes and the development of neurology in Valencia].

PMID- 9147739
TI  - [Primary intraventricular hemorrhage: an analysis of eight cases].
AB  - OBJECTIVE: Primary intraventricular haemorrhage (HIVP) is a rare condition, of
      diverse aetiology and variable course. We present a series of eight cases of HIVP
      diagnosed by CT and analyze the different aetiologies. MATERIALS AND METHODS: A
      retrospective series of 8 cases diagnosed by CT, the risk factors, clinical
      behaviour, complications and prognosis are evaluated. Neuroimaging findings (CT,
      MR and/or DIVAS) are described. RESULTS: The most commonly associated factor is
      arterial hypertension (75%). Clinically, presentation was uniform as evidence of
      sudden intracranial hypertension with signs of meningeal irritation with little
      or no neurological focal signs. The commonest complication was hydrocephalus
      (25%) and the chances of survival in most cases were good. Three causes of
      bleeding were found: an arteriovenous malformation, an aneurysm and a blood
      coagulation disorder. Three hypertensive patients with no obvious cause of
      bleeding had periependimary laguna infarcts. CONCLUSIONS: HIVP is an unusual
      condition of diverse aetiology, uniform clinical presentation and has a good
      short term prognosis. We suggest that pathology of the small vessels, induced by
      hypertension, may play a part in the aetiology of a subgroup of patients with no
      obvious cause of bleeding.

PMID- 9147741
TI  - [Informed consent in neurology].
AB  - Informed consent has remained in the medical tradition but the scale of values
      and human rights have changed. Today the emphasis is on a human being's right to
      autonomy, his personality and power to make decisions. At the same time, the
      doctor-patient relationship has undergone considerable changes. It has evolved
      from one of paternalism based on the old idea of charity, to one in which the
      principle of freedom is prevalent whereby it is the patient who has the right to
      decide the type of medical procedures to be used on him. This idea is recognized
      as such in the General Health Act of 1986. It has therefore become obligatory for
      the medical profession to abide by this Act. To do so the patient must be given
      sufficient information regarding the medical procedures to be applied in his case
      in particular, including all the risks and advantages as well as any possible
      alternatives, so that the patient is able to play a part in choosing the most
      suitable treatment. By law this information must be written down. This is
      essential to create protocols or medical guide-lines to orientate both the
      patient and the judge in the event of a demand action as to whether the medical
      procedure was in accordance with the lex artis or not in each case (lex artis ad
      hoc). We wish to encourage our colleagues to create a model such as we present,
      indicating what we consider to be essential points to be included in guide-lines
      in order to achieve uniform criteria throughout the country thereby facilitating
      the work of medical assessors and judges. We encourage the scientific societies
      involved and the corresponding medical departments to form a working party to
      draw up these medical guide-lines in order to achieve the maximum agreement
      possible.

PMID- 9147742
TI  - [Segmental arteriographic anomalies in migranous cerebral infarct].
AB  - A migranous cerebral infarct (ICM) has the appearance of an ischaemic cerebral
      lesion which occurs during a migraine crisis and is shown by neuroimaging
      techniques to be in the corresponding vascular area. Four young patients are
      described. They fulfilled the clinical and neuroimaging criteria for
      compatibility with ICM and the protocol for the aetiological study of stroke was
      normal. Angiography ruled out other causes of ischaemia (dissection,
      fibromuscular dysplasia, etc.) and showed segmental images of 'vasculitis
      appearance' similar to these described in Call's syndrome, in 'benign
      intracranial angiopathy' and in other intracranial vasculopathies or criteria of
      'reversible segmental cerebral vasoconstriction'. The pathogenic significance, as
      with migraine, is still unknown.

PMID- 9147743
TI  - [Trans-ethmoid meningocele diagnosed in adults. Description of one case].
AB  - The meningocele and encephalocele are extracranial herniation of single meninges
      or meninges with brain tissue, through cranial defect. This pathology can be
      classificated according to contain or localization. The trans-etmoidal
      encephalocele is the 5% of meningoencephaloceles, and they are the 8-19% of all
      neural tube dysraphism. We report a 54 year-old woman with a spontaneous
      rhinorrhea due to an trans-ethmoidal meningocele associate with a recurrent
      meningitis. The computed tomographic (CT) revealed a trans-ethmoidal meningocele
      and she was treated with surgery. In presence of a patient with recurrent
      meningitis is necessary value the possibility of rhinorrhea, and an exhausted
      radiology study will be fulfill for identify the opening in the skull through
      leak CSF, and offer the best treatment. The transetmoidal can be a cause of
      rhinorrhea. The CT scan study of anterior fosa is a good method for diagnostic of
      this pathology, however, the IRM is the election method.

PMID- 9147744
TI  - [Lateral sinus thrombosis in the first three months of pregnancy].
AB  - Thrombosis of the cerebral venous sinuses is characterized by clinical
      pleomorphism and variable pathogenesis. Although there is a relationship with
      pregnancy and especially with the puerperium, occurrence during the first
      trimester of pregnancy is unusual and this may effect the diagnosis and
      treatment. We describe the case of a 33 years-old patient with lateral sinus
      thrombosis in the first trimester of pregnancy. This was diagnosed and followed
      up by magnetic resonance. Investigations as to its aetiology were inconclusive
      and it followed a benign course without anticoagulation. Thrombosis of the venous
      sinuses has been found empirically to be related to states of deficiency of S
      protein, hypercoagulability, anaemia and deshydration during pregnancy, to having
      previously taken contraceptive pills. Behcet's disease, other coagulopathies,
      central or systemic vasculitis, collagen disorders, septic and neoplastic
      disorders and a large number of cases of unknown aetiology. In our patient
      neurological deterioration secondary to a venous infarct or intraparenchymatous
      haemorrhage was not seen. There was full recovery and complete spontaneous
      canalization of the sinus, as shown on posterior cranial angiography. The
      controversial decision to use heparin in thrombosis of the cerebral venous
      sinuses should probably depend on the possible risks and benefits in each
      individual case, taking into account the clinical findings, aetiology and
      topography of the thrombosed sinus.

PMID- 9147745
TI  - [Cerebral hemorrhage after carotid endarterectomy in a young adult].
AB  - INTRODUCTION: Cerebral haemorrhage after carotid endarterectomy is a rare
      complication. It follows 0.5% to 20% of all endarterectomies, but should be borne
      in mind because of the morbidity and mortality seen in most cases. CLINICAL CASE:
      We describe the case of a 42 year old man in whom carotid endarterectomy had been
      done 7 days before to treat a stenosis of 80%. He complained of a sudden onset of
      weakness of the right half of his body and changes in his speech. Physical
      examination showed right inferior facial paresia, right hemiparesia and right
      extensor cutaneous plantar reflex. On admission to the Emergency Department,
      before treatment, blood pressure was 80/60. Carotid auscultation and palpation
      were normal. Cerebral TRC showed a left lenticular haematoma. The patient
      progressed satisfactorily. DISCUSSION/CONCLUSIONS: We review the literature on
      the subject as well as the factors which should be considered as possibly
      predisposing to bleeding after carotid endarterectomy, such as arterial
      hypertension and occlusion or severe stenosis of the contralateral carotid
      artery. The detection of patients with the risk of postendarterectomy bleeding by
      simple noninvasive investigations, such as the transcranial doppler and the
      acetazolamide test, and early diagnosis of a clinical picture compatible with a
      hyperperfusion syndrome may contribute to the relief and prevention of sequelae
      in these patients.

PMID- 9147746
TI  - [Transitory episode of laughter as the initial symptom of an ischemic stroke].
AB  - INTRODUCTION: Pathological laughter occurs in pseudobulbar paralysis, in
      psychiatric disorders and as a sign of convulsions (gelastic crisis). An
      extremely rare form is the "fou rire prodromique' a pathological episode of
      laughter preceding a stroke. The pathogenesis is unknown and classically
      differentiated from gelastic crises. "Fou rire prodromique' has been described in
      subcortical ischaemic or haemorrhagic strokes, not in cortical strokes. CLINICAL
      CASE: We describe a patient with an ischaemic cerebrovascular accident due to
      embolism of the left Sylvian artery. The clinical picture started with a short
      episode of pathological laughter which preceded sensitive aphasia and weakness of
      the right limbs. CONCLUSIONS: We suggest that in the case described it is
      impossible to differentiate between the "fou rire prodromique' and a gelastic
      crisis as a first sign of an embolic cerebrovascular accident.

PMID- 9147747
TI  - [Devic's optic neuromyelitis. Follow-up of the evolution of the medullary lesions
      using magnetic resonance].
AB  - The nosology of Devic's optic neuromyelitis (NMOD) is controversial. Although
      classically considered to be a variety of multiple sclerosis, there are a number
      of differentiating characteristics which would permit classification as a
      separate condition. The evolution of changes in the medulla, as shown by magnetic
      resonance, is described in a patient with recurrent episodes of myelitis and
      optic neuritis. In successive exacerbations widening of the medulla was seen,
      with the appearance of areas of cavitation which later gave rise to atrophy of
      the medulla. During an 18 year follow-up period the symptoms were only of visual
      and medullary pathology, on magnetic resonance no other lesions were found in
      other parts of the central nervous system. The condition corresponded to Devic's
      optic neuromyelitis (NMOD). Whether it is a variant type of multiple sclerosis or
      a distinct entity, NMOD shows differentiating characteristics.

PMID- 9147748
TI  - [Respiratory dyskinesia induced by veralipride].
AB  - We describe the case of a patient whose menopause syndrome was treated with
      veralipride. After four months of this treatment she started to have bucco
      lingual movements and marked dyspnea which caused difficult, irregular breathing
      and severe thoracic discomfort. After the drug was stopped there was progressive
      improvement and disappearance of the symptoms described. When the patient was
      taking a neuroleptic drug (veralipride) she developed bucco-lingual dyskinesia,
      considered to be the commonest late dyskinesia, together with marked respiratory
      dyskinesia. The latter is a type of dyskinesia seldom described, probably because
      it is only detected when it is severe enough to cause functional effects. It may
      pass unnoticed when the disorder is only slight or moderate. In the literature
      there are few references to disorders of movement induced by this drug,
      especially when compared with other benzamides which are frequently involved.
      However, in its mode of action there is a beneficial antigonadotropin activity
      together with an antidopaminergic effect which explains why they may cause such a
      reaction.

PMID- 9147749
TI  - [Thrombosis of the superior longitudinal sinus in patients with AIDS. A review of
      the literature].
AB  - Cerebral dural sinus thrombosis (CSDT) is a rare disease with a high rate of
      mortality. Until now it has not been well-documented in patients with the
      acquired immunodeficiency syndrome (AIDS). Prompt diagnosis is essential for
      initiation of suitable treatment, especially in cases with progressive
      neurological involvement. The diagnostic methods include computed tomography
      (CT), magnetic resonance imaging (MRI) and conventional angiography. MRI and
      magnetic resonance angiography (MRA) have become the methods of choice because of
      their sensitivity and noninvasive nature. An unusual AIDS-patient, who at the
      time of CSDT presentation had an associated toxoplasmosis infection is described.
      To our knowledge, this is the first case of CSDT diagnosed by MRI and MRA in an
      AIDS patient. In the follow-up, MRI and MRA showed the repermeabilitation of the
      sinus thrombosis. Cerebral dural sinus thrombosis should be considered as a
      possible cause of neurological decline in a HIV-patient with central nervous
      system opportunistic infection.

PMID- 9147750
TI  - [Notes for a historical review of Valencian neurology from its beginning until
      1984-1985].

PMID- 9147751
TI  - [Evaluation of nursing care in patients with myasthenia gravis].
AB  - A retrospective study was made of 35 periods of hospital admission between
      January 1985 and September 1995, of 17 patients diagnosed in the Hospital Josep
      Trueta, Girona, as having myasthenia gravis. These were all the patients
      diagnosed as having myasthenia gravis in this ten year period. We studied the
      characteristics of their stay in hospital and evaluated the planning and practice
      of nursing care during these 35 periods. Nursing problems or diagnostic
      difficulties were found on 15 occasions, probably due to lack of knowledge of
      myasthenia gravis. When a patient had dysphagia, nursing care was increased and
      any problems identified. 29.4% of the patients were admitted to the intensive
      care unit. Since this disorder may be very serious, we consider that special
      training should be given to the nurses attending these patients. An understanding
      of this disorder and the possible treatments, complications, drugs, etc. would
      make it possible to give specific, individualized attention which would result in
      a higher standard of care.

PMID- 9147752
TI  - [Analysis of the situation of Valencian neurology by the Commission of Analysis
      of the Quality of Valencian Neurological Society].
AB  - INTRODUCTION: The Comision de Analisis de la Calidad de la Sociedad Valenciana de
      Neurologia has made a proposal of Neurology care requirements, based on the
      findings of various studies done in this region. There studies suggest that there
      should be a proportion of 3 neurologists per 100,000 inhabitants. METHOD: An
      analysis of requirements was made, based on evaluation of the public health
      service, private practice and trainee specialists (MIR) regarding this problem.
      The need for emergency neurological attention, and the place of a hierarchy and a
      system for referral was also considered. RESULTS: It was calculated that 109
      neurologists are required, 11 in Castellon, 63 in Valencia and 35 in Alicante.
      This would mean a proportion of 2,66 neurologists per 100,000 inhabitants in
      Castellon, 2,90 in Valencia and 2,70 in Alicante. The total figure for the whole
      Community would be 2,82 per 100,000 inhabitants. CONCLUSIONS: At the present time
      neurological care is expensive, since a lack of specialists means waiting lists,
      poor patient care and high costs due to inappropriate use of technical resources.

PMID- 9147753
TI  - [Isodense acute cerebral hematoma on computerized tomography].

PMID- 9147754
TI  - [Treatment of autoimmune neuromuscular diseases with intravenous
      immunoglobulins].

PMID- 9147755
TI  - [Interferons in multiple sclerosis].

PMID- 9147756
TI  - [Current indications of botulinum toxin treatment].

PMID- 9147757
TI  - [Current treatment of syringomyelia based on new physiopathological concepts].

PMID- 9147758
TI  - [Thrombolysis in acute ischemic attack].

PMID- 9147759
TI  - [Carotid endarterectomy].
AB  - Carotid endarterectomy has been a controversial matter since its introduction
      more than 40 years ago. In the last decade several clinical trials were performed
      to determine the efficacy of this operation in patients with carotid estenosis
      and hemispheric or ocular ischemic symptoms. In 1991 the interim results of the
      North American Symptomatic Carotid Endarterectomy Trial and the European Carotid
      Surgery Trial were reported, both trials demonstrating the beneficial effects of
      surgery in symptomatic patients with stenosis of greater than 70%. In 1994 the
      Asymptomatic Carotid Atherosclerosis Study reported their interim results in
      patients who have stenosis of greater than 60% in favor of endarterectomy, in
      centers with documented perioperative mortality and morbidity of less than 3%.
      The Asymptomatic Carotid Surgery Trial is still in progress. All this trials have
      restored the confidence on carotid endarterectomy.

PMID- 9147760
TI  - [Carotid angioplasty with cerebral protection and endovascular prosthesis].

PMID- 9147761
TI  - [New antiepileptic drugs].

PMID- 9147762
TI  - [The treatment of migraine].

PMID- 9147763
TI  - [Meta-analysis: trials with melatonin and its effect on the sleep. Letter].

PMID- 9147764
TI  - [Minimal examination of mental functions in healthy Cuban old-aged people.
      Letter].

PMID- 9147765
TI  - [Epidemiology of tuberculosis in the district of Soria (1983-1993): cases with
      neurological involvement. Letter].

PMID- 9147766
TI  - [Physiological calcification of cerebral falx and cluster headache. Letter].

PMID- 9147767
TI  - [Pilomatrixoma and myotonic dystrophy. Letter].

PMID- 9147768
TI  - [Parietal amyotrophy (Silverstein's syndrome). A new case. Letter].

PMID- 9147769
TI  - [Spinal epidural hematoma in anticoagulated patient. Letter].

PMID- 9147770
TI  - [Hemorrhagic transformation of a cerebral infarction without clinical impairment.
      Letter].

PMID- 9147771
TI  - [Cerebral plasticity, sensitive period, early stimulation and infant development.
      Letter].

PMID- 9147772
TI  - [Primary cerebral lymphoma in a immunologically healthy patient. Letter].

PMID- 9147773
TI  - [Isolated hypoglossal nerve palsy as a manifestation of carotid artery
      dissection. Letter].

PMID- 9147774
TI  - [The concept of "authorship" in scientific journals. Letter].

PMID- 9147775
TI  - [When should long-term treatment of epilepsy be started].
AB  - It becomes more and more difficult to decide whether to treat a patient who has
      had a first seizure. Information obtained from retrospective and prospective
      analysis of the natural history of epilepsy, the risk of a second crises
      occurring and the studies showing that the morbidity from seizure is less than
      previously postulated, raise questions about the decision to treat. In this
      study, we analyze the various factors involved in making the decision as to when
      to start long-term treatment of epilepsy. These include: confirmation of the
      seizure, the risk of recurrence, the type of crisis, etiology, age of onset,
      value of the electroencephalogram, classification of the syndrome, predisposing
      or favourable factors, the duration on the crises and the characteristics of the
      patients, as well as the evaluation in each case of the risk or benefit to be
      expected from this treatment. It is again emphasized that two or more crises
      should have occurred, before the diagnosis of epilepsy is established. In
      childhood, there is a general tendency to treat, when there are no negative
      factors or features which indicate a poor prognosis. However, in adults the
      decision is not so clear, and each case has to be decided individually and the
      best treatment agreed by the patient and his doctor. Finally, it is important
      that the patient's family have diazepam available, in case another seizure
      occurs.

PMID- 9147776
TI  - [Which drugs should be chosen for the different types of epilepsy?].
AB  - The selection of an antiepileptic drug is based primarily on its efficacy. When
      the efficacy of several antiepileptic drugs is similar, what is frequently
      observed, their safety, pharmaco-kinetics, and cost should be also considered.
      Efficacy, dose-dependent and idiosyncratic toxicity, pharmacokinetics features,
      and interactions of phenobarbital, phenytoin, carbamazepine, valproate,
      felbamate, gabapentin, lamotrigine and vigabatrin are comparatively analyzed, and
      drugs of choice for generalized epilepsies and partial epilepsies are proposed.
      It is concluded that phenobarbital, primidone and phenytoin are being replaced by
      carbamazepine and valproate as first choice drugs for most types of epilepsies
      due to a similar (and even better) efficacy, besides a better safety profile and
      easier dosing. Features of new antiepileptic drugs make they adequate to be used
      as add-on drugs in treatment-resistant patients: lamotrigine and felbamate are
      effective in Lennox-Gastaut syndrome, and vigabatrin in West syndrome, most of
      the new antiepileptic drugs are well tolerated and show less interactions than
      the standard ones. However, the efficacy and safety of the new antiepileptic
      drugs in monotherapy, and their long-term safety have not been yet established,
      and they will cost more than the standard drugs. Therefore, the new antiepileptic
      drugs are currently considered as second choice drugs, although vigabatrin has
      been proposed as a first choice drug in West syndrome.

PMID- 9147777
TI  - [How often and what type of control tests should be done during long- term anti
      epileptic treatment?].
AB  - During long-term epileptic treatment, it is essential to monitor the efficacy of
      the drugs used. Any adverse effects of this treatment must be detected early or
      preferably avoided. However, the type of control and the frequency with which
      this should be carried out are controversial. All anti-epileptic drugs are
      potentially liable to provoke adverse reactions of different types and degrees.
      Determinations of the blood-levels of anti-epileptic drugs are useful to attain
      optimus drug levels, and to identify any relationship there might be between
      these drugs and possible adverse effects. However, this usefulness varies,
      depending on the particular anti-epileptic drug concerned. Therefore measurement
      as a routine is not justified, but should be undertaken to obtain the answer to
      specific questions. Laboratory analysis of blood to determine liver function,
      blood cell counts, coagulation, etc. is necessary in some cases. This may imply
      problems of interpretation and of cost. Is most cases it is of little help in the
      early detection or prevention of the most serious adverse reactions, which cause
      the greatest mortality. Therefore although such measures are necessary, attention
      should be paid to clinical methods for the early detection of symptoms and signs
      which may indicate the presence of adverse effects. Similarly, EEG should not be
      done as a routine for the assessment of the effect of treatment, but should be
      used when indicated for the follow-up of specific epileptic syndromes. An EEG may
      be useful for prognosis before suspending long-term epileptic treatment.

PMID- 9147778
TI  - [When and how should the long-term anti-epileptic treatment be stopped].
AB  - Although for some decades it has been customary to stop long-term treatment of
      epilepsy in patients who have been free of crises for several years, there is
      still no general agreement as to when, how and in which cases such treatment
      should be stopped. Several factors have to be taken into account when making such
      a decision: the known toxicity of anti-epileptic drugs; the fact that 10-20% of
      the patients on such treatment have recurrences of their epileptic crises and
      that around 25% of the children and 40% of the adults relapse when long-term
      treatment is stopped. On the other hand, factors which reduce the risk of relapse
      have recently been identified. When the psychological benefit of no longer having
      to take anti-epileptic drugs together with their high cost are also considered,
      it would seem advisable to stop treatment when the patient has had no epileptic
      crises for several years. Since there is no significant difference in the
      frequency of relapses when anti-epileptic drugs are suspended 2-5 years after the
      last crises, and these crises are more frequent when paroxystic activity is seen
      on the EEG before stopping the drugs, we recommend that treatment be stopped
      after 2 years free of crises in idiopathic epilepsy, after 3 years with no sign
      of abnormality in the EEG in patients with partial cryptogenic epilepsy and after
      at least 4 years without crises and 2 years of normal EEG in patients with
      partial symptomatic or generalized cryptogenic or symptomatic epilepsy. The
      criteria for suspending drug treatment should take account of the pharmacokinetic
      features and permit EEG control. Therefore we recommend that 40% of the total
      dose be stopped during the first 6 months at a rate of 20% every three months and
      then a further 20% every two months until medication has been stopped completely.

PMID- 9147779
TI  - [When should the pre-operative study of epileptic patients be carried out?].
AB  - There is great controversy as to the best moment for the preoperative study of
      patients with intractable epilepsy. In this study we attempt to give an answer to
      this question based on a review of the literature and personal experience. First
      various problems are analyzed: the epilepsy-lesion relationship; kinds of
      treatment and types of epilepsy: the concept of curative or palliative surgery,
      surgical syndromes, how long epilepsy has been present and the age of the patient
      at the time of operation. With these factors in mind we attempt to analyze the
      clinical situations and determine in each cases the optimum time to carry out any
      possible surgical treatment as a complement or 'part' of the medical treatment of
      these patients as a whole.

PMID- 9147780
TI  - [Experience with Health Quality of Life Questionnaire for the epileptic child
      (CAVE)].
AB  - INTRODUCTION: The practical application of a questionnaire designed to evaluate
      the quality of life of an epileptic child, known as the CAVE test, is described.
      This is the first scale of its kind. The test consists of 8 parameters: conduct,
      attendance at school, learning, independence, social relationships, frequency of
      crises, intensity of crises and parental opinion. Each aspect is given a score,
      from a minimum of 1 point to a maximum of 5 points. MATERIAL AND METHODS: A total
      of 203 tests were carried out. 179 of these were considered to be useful. Nine
      Spanish neuropediatric departments took part in this study. The age limits were
      from 0 to 14 years old. The best results showed a direct relationship to the
      children's age, idiopathic etiology and monotherapy as treatment. The quality of
      life worsened from those with partial simple crises to those with typical
      absences and generalized tonic-clonic crises. The lowest scores were found in
      children with infantile spasms and in those with Lennox-Gastaut syndrome. There
      was a clear statistical relationship between the highest score obtained and the
      best clinical condition, with regard to the frequency and intensity of crises.
      Parental opinion was in keeping with the clinical evaluation of the disorder to a
      certain extent. CONCLUSION: The study is still in progress, so as to interview
      1000 children altogether. Then any modifications considered advisable will be
      made by the multicentre group of the Sociedad Espanola de Neurologia Pediatrica,
      and may be validated internationally.

PMID- 9147781
TI  - [Assessment of Health Quality of Life Scale in the adult with epilepsy (FEGEA)].

PMID- 9147782
TI  - [Civil and criminal responsibility of epileptics].
AB  - Since the new Penal Code has come into force, certain sections have been altered,
      such as those dealing with exculpatory circumstances, and as specialists treating
      patients with possible mental changes, we should be aware that section 20 now
      takes the place of the former section 8. The situation of the epileptic with
      regard to civil and criminal responsibility, has hardly changed. This is not
      surprising in view of current clinico-therapeutic knowledge. Epileptic patients
      are legally able to testify, inherit etc. and also have the obligation to
      compensate for damage they have caused. An attempt is made to define the immunity
      from prosecution of epileptics in accordance with non-static criteria, and to use
      a mixed biological-mental formula, which would make it possible to discover
      whether there was an alteration or anomaly of mental state at the time of the
      criminal offence, which would mean that the patient was unable to understand the
      unlawfulness of his action, or to act in accordance with such understanding. The
      deed itself is considered, without labelling illnesses or persons, seeking a
      simple definition of immunity from prosecution. The epileptic is immune from
      prosecution during a full attack, whilst during the rest of the time each case
      has to be decided individually. We emphasize the necessity of 'declassifying'
      epilepsy as a typical endogenous psychosis, which puts these patients into the
      group of the insane, although this term is no longer included in the new legal
      code.

PMID- 9147783
TI  - [Legal aspects of epilepsy and coexisting psychiatric disorders].
AB  - Major advances in understanding the neurobiology of epilepsy have led to more
      precise diagnosis, early rational treatment with new drugs, useful new
      neurosurgical techniques, etc. This has led to significant control of seizures, a
      marked reduction in concurrent psychopathology, improved quality of life of the
      epileptic patient, the almost complete abolition of old-style institutions for
      these patients, etc. However in spite of greater scientific knowledge about
      epilepsy, this has not led to an equally great advance socially. Old-fashioned
      restrictions and limitations based on mistaken ideas as to the nature of epilepsy
      still remain. Epilepsy is still considered in the same light as the
      psychopathological disorders seen in some epileptics, as a result of different
      variables which are not necessarily related to seizures. Current legal rulings on
      epilepsy, with or without co-existing mental disorder, are reviewed in relation
      to their effect on driving motor vehicles, carrying out military service, the
      condition of minusvalia, the possibility of legal incompetence, and the nullity
      of marriage and of priesthood. It is concluded that although the limitations
      maintained by some statutory requirements are reasonable, it would be fairest to
      abolish restrictions which, in view of present scientific knowledge, are out of
      date and prevent the return to normal and full social integration which should
      prevail for people with epilepsy.

PMID- 9147784
TI  - [Cerebral mapping in patients with dementia of Alzheimer's type].
AB  - INTRODUCTION: The electric cerebral activity maps complement the conventional
      electroencefalography quantifying electric cerebral activity. One of the
      applications is in Alzheimer's dementia. OBJECT: The object of this study is to
      analyse the differences in the electric cerebral activity, by means a quantified
      EEG, in DAT and SDAT when compared with a control group of the same age. MATERIAL
      AND METHODS: Thirty patients meeting the criteria of probabledementia (NINCDS
      ADRDA) in the senile (n = 19) and presenile (n = 11) form were studied. They were
      compared with a control group of the same age, 20 individuals older than and 17
      younger than 65. RESULTS: The patients suffering from senile dementia as well as
      those suffering from the presenile form showed a significative increase of the
      delta and theta bands. On the other hand, a significant reduction of the alfa
      frequency bands and mainly those of beta was observed in the patients with ADT
      but not in the ADST ones. The significant increase of the slow bands in ADT and
      ADST and the significant decrease of the fast bands in ADT have been found in
      wide areas. Topographically the biggest affect has been registered in the frontal
      regions for the beta bands in ADT. CONCLUSIONS: The differences found in the
      electrical activity, depending on the age, would support Alzheimer's disease
      heterogeneity.

PMID- 9147785
TI  - [Neuronal toxicity of human recombinant interleukin-2 in rats. Morphological and
      behavioral validation].
AB  - INTRODUCTION AND OBJECTIVE: The memory impairment which accompanies the aging
      process is a manifestation of diminished cognitive function. This is intimately
      related to neuropathological and biochemical changes in cholinergic areas of
      central nervous system (CNS). Cytokines, first described as immunoregulators, are
      also implied in defense reactions of the brain. Some studies on the action of IL
      2 on the CNS suggest an action blocking the release of acetylcholine in the
      hippocampus. MATERIAL AND METHODS: We have studied the possible central
      neurotoxic effect of this soluble factor using the chronic intraperitoneal
      infusion of human recombinant IL-2 (hr-IL 2) to young and old Sprague Dawley
      rats. RESULTS AND CONCLUSIONS: The results do not show an in vivo action of IL-2
      on the cholinergic function but are consistent with the probable role of this
      cytokine in the senescent cognitive impairment, in particular the age-related
      loss of spatial memory and/or during the evolution of neurodegenerative related
      process.

PMID- 9147786
TI  - [Complex partial seizures: the localization value of automatisms].
AB  - INTRODUCTION: The clinical findings in complex partial crises may help our
      understanding of the different foci and vias of epileptogenesis. MATERIAL AND
      METHODS: We analyse automatisms and findings on EEG and neuroimaging in 151
      patients with different types of partial epilepsy, seeking to establish a
      possible correlation between the type of automatism and cerebral localization.
      RESULTS AND CONCLUSIONS: The relative frequency of automatisms was: oro
      alimentary 30%, mimicking 11%, gestures 35%, ambulatory 19% and verbal 13%. There
      was a statistically significant difference between the type of automatism and the
      topography of the EEG and neuroimaging findings. There were more gesture and oro
      alimentary automatisms in patients with temporal anomalies, both on EEG and on
      neuroimaging, than in those with extratemporal alterations.

PMID- 9147787
TI  - [Cerebral blood flow study using SPECT in patients with memory disorders].
AB  - INTRODUCTION: Global amnesia (AG) is a dysfunction of memory, in which there is a
      sudden incapacity to remember recent events and assimilate new information. The
      aetiology is currently under discussion. The main hypotheses under consideration
      are an ischemic mechanism and an epileptic mechanism. OBJECTIVE: To study the
      cerebral blood flow in patients with temporary global amnesia (AGT) or permanent
      global amnesia (AGP) using functional neuroimaging techniques. MATERIAL AND
      METHODS: Four patients were studied. Two had severe alterations of fixation
      memory which had been present for months. The other two had a sudden loss of
      recent memory, although space-person orientation and immediate memory remained
      normal. In all cases the cerebral blood flow (FSC), was assessed by single photon
      emission tomography (SPECT), using Tc-HMPAO as the radio tracer. RESULTS: We
      describe 4 patients, 2 men and 2 women aged between 42 and 64.2 with AGT and the
      others with AGP. On SPECT there was temporal hypoperfusion in all 4 patients. In
      2 cases there was associated parietal hypoperfusion and in 1 case there was
      frontal hypoperfusion. CONCLUSIONS: These findings suggest that AGT and AGP are
      of vascular origin and that SPECT is a useful diagnostic technique in patients
      with AG.

PMID- 9147788
TI  - [Menkes' disease: anatomo-clinical presentation of a case].
AB  - We describe a case of Menke's disease with severe neurological involvement,
      convulsive crises and characteristic hair anomalies (scanty, fragile,
      macroscopically hypopigmented and microscopically kinked) which led to rapid
      diagnosis. Vascular abnormalities with elongated, twisted arteries, skeletal
      abnormalities (more wormian cranial bones than usual, lateral spurs of
      metaphyses) and vesicle diverticuli. Electron microscopy of skeletal muscle
      showed concentrically laminated bodies, possibly of mitochondrial origin.
      Respiratory chain enzyme activity was normal. The patient died at the age of two
      and a half. On necropsy, histological abnormalities characteristics of the
      illness were seen (loss of neurones in the granular layer of the cerebellum, the
      neurones of Purkinje had thickening of the dendrites which spread out in the form
      of a weeping willow, reduplication and fragmentation of the internal elastic
      layer of muscle arteries). In the cortex of the cerebellum mega-mitochondria with
      electron-dense bodies, were seen on electron microscopy. This is the first case
      of Menke's disease described in the Spanish literature which includes pathology
      and electron microscope studies.

PMID- 9147789
TI  - [Reversible leukoencephalopathy related to cyclosporin treatment].
AB  - INTRODUCTION: At the present time cyclosporin is the most commonly used
      immunodepressive drug for the prevention of transplant rejection. Although the
      mechanism by which cerebral dysfunction occurs is not well understood, it has
      been noted that the clinical and radiological characteristics of cyclosporin
      neurotoxicity, which may occur even when the blood levels of the drugs are within
      the therapeutic range, are very similar to those of hypertensive encephalopathy
      and also resolve when the blood pressure drops. CASE CLINIC: A 35 year old woman,
      treated with high doses of cyclosporin for a bone marrow transplant, presented
      with progressive headache, drowsiness, blurred vision and convulsions which
      coincided with a rapid rise in blood pressure. After antihypertensive treatment
      full recovery (of all symptoms) was seen. Neuro-radiological studies showed
      extensive changes in the white matter, mainly in the posterior cerebral regions
      that were not enhanced after contrast. The changes were compatible with oedema. A
      magnetic resonance study done two years later was completely normal. CONCLUSIONS:
      In this clinical report the aetiology and the clinical and radiological
      characteristics of the neurotoxicity due to cyclosporin are discussed.

PMID- 9147790
TI  - [Nystagmus as uncommon neurological manifestation of sphenoidal sinusitis.
      Letter].

PMID- 9147791
TI  - [Posterior columns syndrome as an onset form of Guillain-Barre syndrome. Letter].

PMID- 9147792
TI  - [Plasmatic determination of natriuretic peptides in demented patients. Letter].

PMID- 9147793
TI  - [Future scenarios of HIV-AIDS: from the "event" disease to diffuse chronicity.
      From the moral stigma to the central zones of social vulnerability].

PMID- 9147794
TI  - [Epidemiology of cervical invasive cancer in the Gerona health area in 1980-1989.
      Cancer registry of Gerona].
AB  - BACKGROUND: The goal of the present work is to carry out a descriptive study
      about the impact of invasive cervical cancer in the area of Gerona, Spain.
      METHODS: Using data from the population based cancer registry of Gerona for the
      period 1980-89, several incidence rates were calculated. Incidence trends,
      demographical distribution and survival according of different variables were
      analyzed. RESULTS: The average age in which the disease appears was 57 +/- 14
      years; the most frequent histological type was the squamous cell carcinoma; 51%
      of the cases were women born in Cataluna and the remaining percentage corresponds
      to women from others regions and foreigners. At the moment of diagnosis, el 36%
      of the cases were local, 34% were regional and 23% disseminated. Crude,
      standardized and truncated (35-64 years) incidence rates, during 1980 to 1989
      were de 8.2, 6.2 and 13.7 cases x 105 women respectively. According to the
      cumulative rate, 1 in 150 women will have this cancer by age 74. No increase of
      the trend has been found, however, a significative subincidence has been observed
      in rural areas. 5-years survival rates is 48.5% and was significantly associated
      with stage at diagnosis, but age was not. CONCLUSION: From an international
      viewpoint, Gerona is a low incident area for this tumour and no rising trend has
      been found. The subincidence in rural areas may suggest a different exposition to
      risk factors, although certain aspects such as accessibility to health care
      services, the defining of rural and urban areas and the existence of migrations
      should be considered. Finally, the lower survival rate with regard to other
      countries could be attributed to the presence of more advanced stages, which
      emphasizes the importance that the early diagnosis of this tumour has.

PMID- 9147795
TI  - [Evaluation of the effectiveness of a program of detection of asymptomatic
      Chlamydia trachomatis infection in women].
AB  - BACKGROUND: Chlamydia Trachomatis is at present the most prevalent pathogenic
      agent among the causes of sexually transmitted diseases in developed countries,
      and has reached epidemic proportions in some of them. These infections can give
      rise to a considerable number of complications, many with very serious
      consequences. Given that, in addition, a great number of cases are asymptomatic,
      a general consensus exists about the convenience of carrying out screening
      programmes. The aim of this study is to accomplish the first stage of the
      screening programme of asymptomatic infection by C. trachomatis in women who seek
      help at a family planning centre. METHODS: A descriptive study to determine the
      prevalence each year of the period studied, an analysis of its temporal tendency
      and the assessment of the programme effectiveness in terms of a proportional
      reduction in prevalence. A total number of 6.746 women were included, who
      attended the family planning centre for a regular checkup or contraceptive advice
      between January 1991 and December 1993. RESULTS: The programme showed a global
      effectiveness rate of 80%, with a reduction in prevalence from 5.1% in 1990 to
      1.0% in 1993. A significant fall was observed in all the categories analyzed,
      except for women using prophylactics and those with higher education.
      CONCLUSIONS: The programme achieves its objectives very effectively.
      Nevertheless, it would be advisable to evaluate its efficiency together with a
      cost-analysis, since by reducing prevalence, the positive estimated value of the
      test considerably decreases, which raises the cost of a single case detection.

PMID- 9147796
TI  - [Do physicians' strikes influence the utilization profile of hospital emergency
      services?].
AB  - BACKGROUND: To assess the differences in appropriateness of consultations and
      demographic outline of people attended in a hospital emergency facility (HEP)
      along the hospital physicians strike period in spring 1995. METHODS:
      Observational cross-sectional study in Health Area 1 in the province of Badajoz.
      8964 patients assisted along the strike period were compared with 8024 attended
      in the same period of 1994 (no strike). RESULTS: The patients average was 169.13
      (SD 27.35) a day in the strike period, during the control period this mean was
      151.39 (SD 19.78) patients a day (p < 0.001). Demographic variables of patients
      were similar in both groups, with similar mean ages and gender proportion in all
      age and residence site groups. Most of patients went to the HEF self-promoted
      (70.1% and 65.8%) and without ambulance (92% and 90.8%) in both periods (strike
      and control). The outcome of medical care was home discharge in 85.35% during the
      strike period and 83.81% in the control period, with admission rates of 13.1% and
      14.15% (p < 0.01). CONCLUSIONS: There are no significant differences in the HEF
      use features completely explained by the physicians strike.

PMID- 9147797
TI  - [Hypertensive patients treated in Spain, 1990-1993].
AB  - BACKGROUND: The main goal of our work was to gain knowledge from the pharmaco
      epidemiological perspective on the use of anti-hypertensive drugs in our country,
      in order to obtain a rough estimation of the number of hypertensive patients
      under treatment in various Autonomous Communities. METHODS: The data regarding
      the consumption of hypertensive drugs (mono-medicines) from 1990 to 1993 have
      been obtained from the Vice-Directorate General for Treatment and Pharmaceutical
      Planning. The methodology used to calculate the "Estimated Prevalence Patient
      day" under treatment with these drugs is based on the WHO recommendations for the
      Studies on the use of Medicines. Estimated Prevalence of Patient-day (EPPD) has
      been calculated by using the Defined Daily Dosage of each anti-hypertensive drug.
      RESULTS: The number of hypertensive patients under treatment with these drugs was
      1.763.937, 1.966.396, 2.226.225 and 2.435.294, from 1990 to 1993, respectively.
      At the end of our study, in 1993, the number of hypertensive patients under
      treatment in Spain is nearly 50% of the total number of hypertensive patients.
      There are some differences amongst regions; thus, the Autonomous Communities of
      Aragon, Castilla-La Mancha, Cataluna, Pais Valenciano and Murcia are noticeable
      as regions where the number of hypertensive patients treated exceeds the national
      average. CONCLUSIONS: The number of hypertensive patients under treatment has
      considerably increased between 1990 to 1993 (+ 40%). An increase is observed in
      the number of hypertensive patients treated with calcium antagonists and ECA
      inhibitors and a decrease is observed in the proportion of hypertensive patients
      under treatment with Beta-blockers and diuretics.

PMID- 9147799
TI  - HABAC is alive and well, but needs more veterinarians as members.

PMID- 9147800
TI  - A "masculinist" historical perspective of nursing.

PMID- 9147798
TI  - [Spatial/temporal analysis of the incidence of certain cancers by sites in
      Quebec: 1984-1986 and 1989-1991].
AB  - Basing our views on recent works of an Ontarian research group, we analyze the
      profiles of incidence of the main types of cancers observed in the province of
      Quebec for the periods 1984-1986 and 1989-1991. Using the Quebec Tumors Registry,
      we have calculated standardized incidence rates according to sex for each of the
      32 departments of community health in the province. A geographical analysis of
      cancers was conducted via two methods of spatial autocorrelation (SA). Many
      cancer sites (i.e., breast, lung, stomach) show a positive SA (p < 0.05),
      indicating an aggregation of cases. Several aggregation schemes observed in
      Quebec resemble those observed in Ontario. In women, the highest incidence rate
      increases are in leukemia and lung cancer; in men, prostate cancer and leukemia
      show the highest increase of rates (p < 0.01). The consistency of our
      observations with those of the Ontario group is discussed.

PMID- 9147801
TI  - Special report east meets west.

PMID- 9147802
TI  - Harm reduction: a realistic approach toward injection drug users.
AB  - The injection use of illicit drugs is a major mode of HIV transmission in the
      heterosexual population. Indeed, because HIV is transmitted from injection drug
      users to their sexual partners and their children, there is widespread
      acknowledgement that controlling HIV infection in the general community may
      depend on controlling it in injection drug users. Unfortunately, a moralistic
      attitude toward illicit drugs and their users all too often deters health
      professionals from taking preventive action. This impractical attitude holds that
      stopping illicit drug use is the only answer. In today's age of AIDS, it's a
      dangerously simplistic stance.

PMID- 9147803
TI  - Restructuring hospitals, restructuring nursing.
AB  - The global economy is in the depths of recession. Organizations from virtually
      every industry, including manufacturing and service, have responded by reducing
      expenses and cutting operational costs. Health care restructuring is one result
      of the new economy. Hospitals worldwide have been flattening organizational
      charts and reducing costs. Downsizing, rightsizing, restructuring--whatever term
      is used, the message is the same: people are a cost to be reduced.

PMID- 9147804
TI  - Airevac nurses in war zones.
AB  - Since early 1993, the flight nurses and flight medical assistants of the Canadian
      Air Force (CAF) have been evacuating casualties from the war zones of Bosnia,
      Somalia and Rwanda. It's the first time since the Korean War that Canadian
      medical crews have done airevacs from a theatre of war, and the evacuations have
      been demanding--and eye-opening--experiences.

PMID- 9147805
TI  - Successful tracheal weaning.
AB  - In 1994, neuroscience nurses and neurosurgeons at St. Boniface General Hospital
      and the Health Sciences Centre in Winnipeg completed a study on tracheostomy
      weaning. This collaborative effort was initiated in response to a perceived
      clinical need--weaning difficulties in our neurological and neurosurgical
      patients--and was the first step along the road to implementing a standardized
      weaning procedure.

PMID- 9147806
TI  - [Future shock of the new graduates].
AB  - How do new nursing graduates take their place in a changing workforce with
      continuing changes to health care delivery and budgetary cuts in health care
      institutions? To understand the importance of successfully adjusting to new
      employment and the rate at which new graduates leave the profession, it is
      necessary to understand what goes on during their first months on the job. This
      qualitative research project was conducted over an 18-month period and focused on
      the initial work adjustment period. It involved 31 nursing graduates working in
      five different hospitals in Quebec's Estrie Region. The results indicate new
      graduates discover very early on that they've entered a brave new world where the
      work situation proves to be very different from what they have been taught. There
      is still a wide gap between theory and practice, and rarely are the students'
      expectations met with regards to providing holistic care, communicating with
      patients and establishing care plans. The students' precarious work situation as
      occasional nurses on call becomes a way of life. In the absence of job
      opportunities, they must develop adjustment strategies to ensure professional
      survival. A new type of nurse is emerging--the "functional nurse." The functional
      nurse learns to be available at all times, to provide care with no continuity and
      without any hope of ever belonging to a unit. Meanwhile, she questions herself
      about the quality of care she is giving and her future as a nurse.

PMID- 9147807
TI  - Nurses who work in labour and delivery.

PMID- 9147808
TI  - Diabetes care moves closer to home.

PMID- 9147809
TI  - Developing a staff protection program.

PMID- 9147810
TI  - Rekindling the flames of hope.

PMID- 9147811
TI  - National standards for health care.

PMID- 9147812
TI  - Two reasons to feel good.

PMID- 9147813
TI  - Ending an era of education.
AB  - In the spring of 1998, the sixth and final class in the collaborative nursing
      program of the University of British Columbia (UBC) and the Vancouver General
      Hospital (VGH) will graduate, thus ending the almost 100-year history of nursing
      education at the hospital.

PMID- 9147814
TI  - [Living with dignity until the end].
AB  - The author of this article tackles some end-of-life issues and presents his
      thoughts on euthanasia and assisted suicide. He defends the idea of "living with
      dignity to the end," and sees death itself as a natural process that the client
      does not always want shortened. Drawing on experience from his palliative care
      practice the author establishes a link between heroic measures, pain alleviation
      and false hope. He also encourages ethical debates by framing questions common to
      the daily work of nurses. The author has unprecedented insight into the nurse's
      role as an observer of change in the condition of the dying person and her/his
      interpretation of the needs, fears, happiness and concerns of that person. The
      author also promotes professional collaboration, without prejudice or
      discrimination, and the alleviation of pain using the endiess range of palliative
      precautions. His approach to end-of-life offers a message of hope to the living.

PMID- 9147815
TI  - [A baccalaureate program born from a university and a college collaboration].
AB  - Ontario health care reform has necessitated many changes in the nursing
      profession. To practice effectively, nurses must readjust their roles and
      training. This article discusses a revised bachelor of nursing program that is
      the result of collaboration between two teams of educators from the French
      language division of the School of Nursing at Laurentian University and the
      Nursing Program at College Boreal in Sudbury, Ontario. It describes the
      preliminary stages of program development, the major players, the underlying
      philosophy and an overview of the program in each of the four years of study. The
      program, which includes the option of earning a college diploma at the end of the
      third year, is slated for introduction in the fall of 1997.

PMID- 9147816
TI  - Neuropathogenesis of simian immunodeficiency virus infection in macaque monkeys.
AB  - Patients infected with human immunodeficiency virus (HIV) develop immunologic
      dysfunction and multiorgan inflammatory diseases directly associated with HIV-1
      infection. Of these inflammatory diseases, the most devastating to the HIV
      infected patient is involvement of the central nervous system (CNS). The
      pathogenesis of the clinical syndrome observed in these patients, termed HIV
      associated dementia, remains poorly understood. However, as most of the
      detectable virus in the CNS is in cells of monocyte/macrophage lineage, it is
      clear that penetration of the blood-brain barrier by HIV-1 and the subsequent
      influx of monocytes into the brain are crucial components in the
      neuropathogenesis of HIV-associated dementia. Using the SIV-infected macaque
      model of acquired immunodeficiency disease, much has been learned about viral
      neuroinvasion occurring soon after experimental infection. The aim of this review
      is to discuss these recent advances and provide insight into plausible mechanisms
      for monocyte entry into the CNS.

PMID- 9147817
TI  - Isolation and long-term culture of primary ocular human immunodeficiency virus
      type 1 isolates in primary astrocytes.
AB  - Vitreous specimens from 14 HIV-1 infected persons undergoing medically indicated
      vitrectomy were assayed for the presence of infectious HIV-1 and viral tropism.
      Human primary fetal astrocytes, adult lymphocytes, or macrophages were exposed to
      vitreous in culture and and cells were then assayed for HIV-1 DNA by polymerase
      chain reaction amplification. We found that 11 of 14 patients tested carried
      ocular HIV-1 which replicated in one or more primary cell types; of the 13
      vitreous samples tested in astrocytes, eight contained transmissible HIV-1. The
      three patients with no culturable ocular virus were in antiviral therapy at the
      time of vitrectomy. Comparison of envelope V3 sequences from astrocytes infected
      in culture to that in uncultured blood cells revealed 21% sequence divergence
      indicating that ocular HIV-1 transmitted to astrocytes was not recently derived
      from virus present in the blood. Two ocular samples transmissible to astrocytes
      were tested further and found capable of sustained replication by serial passage
      to uninfected astrocytes. However, the viral structural proteins produced by
      infected astrocytes were abnormal, p24 was absent and higher molecular weight Gag
      proteins were present. We conclude that the eye is a central nervous system
      compartment which frequently contains HIV-1 capable of replication in human
      astrocytes.

PMID- 9147818
TI  - Transactivation of proenkephalin gene by HTLV-1 tax1 protein in glial cells:
      involvement of Fos/Jun complex at an AP-1 element in the proenkephalin gene
      promoter.
AB  - The human T-cell lymphotropic virus type 1 (HTLV-1), an etiologic agent for adult
      T-cell leukemia, is strongly associated with tropical spastic paraparesis, a
      chronic neurological disease. The HTLV-1 genome encodes a protein, tax1, an
      autoregulator of enhanced viral RNA transcription, that also
      transactivates/represses certain cellular gene promoters. Enkephalins are opioid
      peptides that function as neurotransmitters and neuroimmunomodulators. We earlier
      reported that the proenkephalin gene is transactivated by tax1 protein in glial
      cells. The nucleotide sequence upstream of -190 base pairs in the proenkephalin
      gene promoter is necessary for maximal transactivation by tax1 while the sequence
      downstream of -190 bp confers modest activation by tax1. We investigated the
      cellular transcription factors in tax1 expressing glial cells that associate with
      the proenkephalin promoter and herein demonstrate the enhanced interaction and
      involvement of c-Fos/c-Jun proteins in the complexes formed at the AP-1 site. The
      HTLV-1 tax1 expressing stable glial cell lines produced functional tax1 protein
      that increased the expression of endogenous proenkephalin gene. The comparative
      electrophoretic mobility shift and 'supershift' analysis using specific
      antibodies indicated the enhanced presence of c-Fos and c-Jun proteins in the
      DNA: protein complex formed at the AP-1 site. The c-Fos protein expression
      significantly increased in the tax1 expressing glial cells. The tax1 induced c
      Fos protein levels and the concurrently increased association of c-Fos/c-Jun
      transcription factors at the AP-1 site imply a strong functional significance in
      the activation of proenkephalin gene expression in tax1 expressing glial cells.

PMID- 9147819
TI  - Establishment and characterization of conditionally immortalized astrocytes to
      study their interaction with ts1, a neuropathogenic mutant of Moloney murine
      leukemia virus.
AB  - The cytopathic infection of primary astrocytes with ts1, a neuroimmunopathogenic
      mutant of Moloney murine leukemia virus (MuLV), has been correlated to
      intracellular accumulation of viral precursor envelope protein gPr80env. To
      further study this specific virus-astrocyte interaction in a homogenous
      population, several immortal astrocyte lines were established from neonatal FVB/N
      mice using the temperature-sensitive SV40 tsA58 T antigen. These cells expressed
      glial fibrillary acidic protein, vimentin and T antigen; appeared nontransformed;
      were star-shape with long processes. They were susceptible to ts1 infection and
      suffered a cytopathic effect similar to that caused by ts1 infection of primary
      astrocytes. This cytopathic effect was characterized by growth inhibition, loss
      of cell processes and syncytium formation. Some cells also rounded up, formed
      mini cells and became detached from the culture dish. As in primary astrocytes,
      the processing of gPr80env in the immortalized astrocytes was inefficient. Since
      the envelope proteins interact with the ecotropic MuLV receptor both
      intracellularly and on the cell surface and since the receptor has been shown to
      be an arginine transporter, we attempted to determine the effect of ts1 on
      arginine uptake by these cells. Our results showed that in both immortalized and
      primary astrocytes, ts1 infection reduced the uptake of arginine more than did
      wild-type virus infection. Since arginine localizes predominantly in astrocytes
      in the CNS and has diverse functions, the decrease of arginine uptake in ts1
      infected astrocytes may alter the metabolism of these cells, leading to
      impairment of their functions.

PMID- 9147820
TI  - Susceptibility to a neurotropic virus and its changing distribution in the
      developing brain is a function of CNS maturity.
AB  - Many major physiological changes occur within the rodent central nervous system
      (CNS) during the first few postnatal weeks. These include axonogenesis,
      synaptogenesis and myelination. Concomitant with CNS development over this
      period, there is a decrease in susceptibility to many neurotropic virus
      infections in that infection of suckling animals results in lethal encephalitis
      whereas infection of weanling animals is not lethal. The events underlying this
      dramatic change in susceptibility have been unclear. Here we demonstrate that age
      related virulence of the neurotrophic alphavirus, Semliki Forest virus is
      dependent upon ability of the infection to spread in the CNS. This is not
      determined by maturity of interferon, or specific immune responses or the blood
      brain barrier, but by maturity of neuronal systems. Detailed study of the course
      of infection in the cortex, hippocampus and cerebellum during their postnatal
      development indicates that as these and other neuronal systems mature they become
      resistant to spread of the virus and the pattern of infection changes from
      widespread to focal.

PMID- 9147821
TI  - Differential tropism of pseudorabies virus for sensory neurons in the cat.
AB  - The permissiveness of cat motor and sensory systems to infection by pseudorabies
      virus (PRV) was examined. Eight adult cats of both sexes received injections of a
      virulent strain of PRV (PRV-Becker) into either the diaphragm or neck
      musculature. Temporal analysis of the replication and transynaptic passage of
      virus in each experimental paradigm revealed that sensory neurons in the dorsal
      root ganglia were more susceptible to infection than motor neurons. Only
      scattered motor neurons displayed productive replication of virus at
      postinoculation intervals extending to 192 h whereas robust replication of virus
      in neurons in the dorsal root ganglia and dorsal horn of the spinal cord was
      apparent as early as 96 h post inoculation. The data demonstrate that
      functionally distinct populations of neurons in the cat are differentially
      permissive to infection and transneuronal transport of PRV.

PMID- 9147822
TI  - Decontamination of Creutzfeldt-Jakob disease and other transmissible agents.
AB  - The bovine spongiform encephalopathy (BSE) epidemic in cows, and the recent BSE
      linked human infections, present new public health problems. More rigorous
      measures are needed to prevent additional transmissions. Tissue from established
      but undiagnosed human infections can contaminate medical supplies and
      instruments. We tested guanidine thiocyanate (GdnSCN) solutions and found them to
      be highly effective in disrupting the infectious agent, even in very complex
      tissues such as whole brain. It may be prudent now to use this reagent routinely
      in surgical and other relevant settings.

PMID- 9147823
TI  - Persistence of neurotropic JC virus DNA in hamster tissues six months after
      intracerebral inoculation.
AB  - Immunostaining and polymerase chain reaction (PCR) methods were used to examine
      tissues from 18 6-month-old hamsters intracerebrally inoculated with JC virus
      (JCV) as newborns. JCV DNA was detected in all hamster brains and urinary
      bladders, as well as in most kidney, adrenal gland and pancreas samples. While
      results from reverse transcription PCR (RNA PCR) and immunostaining suggest that
      T antigen transcription and protein expression were restricted to the brain, the
      DNA suggests that intracerebrally inoculated JCV enters the systemic circulation
      and latently infects organs in a tissue specific manner.

PMID- 9147824
TI  - Further observations on coronavirus infection of primate CNS.
AB  - Previously, we demonstrated that intracerebral (IC) inoculation of a murine
      coronavirus, MHV-JHM, into two species of primates can result in acute
      encephalomyelitis (Murray et al., 1992a). Infectious virus isolated from acutely
      infected animals, designated JHM-OMp1, was inoculated IC into a second group of
      monkeys. In this report we describe observations on the acutely infected animals
      and those surviving the acute infection were sacrificed at later times post
      infection. Results from dual in situ hybridization/immunohistochemistry screening
      of tissues show that astrocytes are target cells in white matter lesions during
      acute infection. In animals sacrificed 150 days post-infection, areas of
      demyelinated gliotic lesions, prominent in the spinal cord, were seen throughout
      the neuraxis. No virus products were detected in these late-infection lesions.

PMID- 9147825
TI  - Genomic and template RNA transcription in a model of persistent enteroviral
      infection.
AB  - Enteroviruses have been implicated in persistent infections of the nervous system
      and in certain paralytic motor neuron syndromes. Enteroviral persistence may
      depend on defective transcription, resulting in the abnormal production of equal
      amounts of genomic and template RNA strands rather than the normal ratio of 60
      100:1. An in vitro model of a persistent coxsackie virus in human skeletal muscle
      cells was investigated using in situ hybridisation and a semiquantitative
      parallel, complementary, reverse transcriptase polymerase chain reaction. The
      ratio of genomic to template RNA was found to be approximately 60:1. We conclude
      that enteroviral persistence in this in vitro model is not dependent on altered
      transcription. In vivo, other viral and host factors should be considered.

PMID- 9147826
TI  - Myelitis associated with influenza A virus infection.
AB  - We report a patient presenting with myelitis after respiratory symptoms. A high
      level of antibodies to influenza A virus was measured in serum and cerebrospinal
      fluid (CSF), and the serum/CSF antibody ratio was 1.7, suggesting specific
      antibody production in the central nervous system. Magnetic resonance imaging of
      the spinal canal showed a contrast-enhanced swelling on the cervical medulla.
      Such a case would have warranted the use of antiviral therapy and calls to mind
      the neurotropic potential of influenza A viruses.

PMID- 9147827
TI  - HIV-1 gp120 does not induce Quinolinic acid production by macrophages.

PMID- 9147828
TI  - Proceedings of the 2nd International Congress on Food and Cancer Prevention. Ede,
      The Netherlands, May 19-22, 1996.

PMID- 9147829
TI  - The relation of childhood personality types to adolescent behavior and
      development: a longitudinal study of Icelandic children.
AB  - The relation of childhood personality types, or configurations of personality
      traits, to adolescent development was examined. Three personality types were
      identified in an inverse factor analysis of California Child Q-Sort data on 128
      Icelandic 7-year-olds: resilient, overcontrolled, and undercontrolled. Growth
      curve analyses demonstrated that in comparison to children of the other 2 types,
      children of the resilient personality type had higher levels of academic
      achievement and lower levels of concentration problems throughout adolescence;
      resilient children also developed sophisticated friendship reasoning and an
      internal locus of control more quickly. Children of the overcontrolled type were
      found to be more prone to social withdrawal and low levels of self-esteem during
      adolescence than children of the other 2 types. In contrast to the other 2 types,
      children classified as undercontrolled showed an increase in aggressive behavior
      in adolescence. Implications of the findings for research on personality
      development are discussed.

PMID- 9147830
TI  - Antecedents of adult interpersonal functioning: effects of individual differences
      in age 3 temperament.
AB  - We examined whether temperamental differences at age 3 are linked to
      interpersonal functioning in young adulthood. In a sample of over 900 children,
      we identified 5 distinct groups of children based on behavioral observations:
      Well-adjusted, undercontrolled, reserved, confident, and inhibited. At age 21, we
      assessed the children's interpersonal functioning in 4 social contexts: in the
      social network, at home, in romantic relationships, and at work. We found three
      patterns of relations: (a) Well-adjusted, reserved, and confident children
      defined a heterogeneous range of normative adult interpersonal behavior, (b)
      inhibited children had lower levels of social support but normative adjustment in
      romantic relationships and at work, and (c) undercontrolled children had lower
      levels of adjustment and greater interpersonal conflict across adult social
      contexts.

PMID- 9147831
TI  - Infant emotionality, parenting, and 3-year inhibition: exploring stability and
      lawful discontinuity in a male sample.
AB  - In this study, the authors examine temperament (12-13 months) and mothering and
      fathering (15, 21, 27, 33 months) antecedents of inhibition of children at age 3
      years prospectively in a sample of 125 firstborn boys and retrospectively in only
      the most and least inhibited children. High negativity coupled with low
      positivity in infancy predicted high inhibition, as did parenting that was
      supportive (e.g., high sensitivity, low intrusiveness). Parenting appeared more
      influential in the case of children who were highly negative as infants. The
      importance of distinguishing positive and negative emotionality in infancy and of
      studying mothering and fathering are discussed.

PMID- 9147832
TI  - Multiple pathways to conscience for children with different temperaments: from
      toddlerhood to age 5.
AB  - This research extends longitudinally findings on child temperament as a moderator
      of the impact of socialization on conscience development, reported previously for
      contemporaneous data at toddler age. Children's temperament and maternal
      socialization at Time 1 (n = 103, aged 2-3 years) were considered predictors of
      future conscience, assessed using new observational and narrative measures. The
      moderation model was supported for predicting conscience at Time 2 (n = 99, age
      4), and, to a lesser extent, at Time 3 (n = 90, age 5). For children fearful as
      toddlers, maternal gentle discipline, presumably capitalizing on the optimal
      level of anxious arousal, promoted conscience at Time 2. For children fearless as
      toddlers, perhaps insufficiently aroused by gentle discipline, alternative
      socialization mechanisms, presumably capitalizing on mother-child positive
      orientation (secure attachment, maternal responsiveness), promoted conscience at
      Times 2 and 3. Developmental interplay of temperament and socialization in
      emerging morality is discussed.

PMID- 9147833
TI  - Do extracurricular activities protect against early school dropout?
AB  - This study examined the relation between involvement in school-based
      extracurricular activities and early school dropout. Longitudinal assessments
      were completed for 392 adolescents (206 girls, 186 boys) who were initially
      interviewed during 7th grade and followed up annually to 12th grade. A person
      oriented cluster analysis based on Interpersonal Competence Scale ratings from
      teachers in middle schools (i.e., 7th-8th grades) identified configurations of
      boys and girls who differed in social-academic competence. Early school dropout
      was defined as failure to complete the 11th grade. Findings indicate that the
      school dropout rate among at-risk students was markedly lower for students who
      had earlier participated in extracurricular activities compared with those who
      did not participate (p < .001). However, extracurricular involvement was only
      modestly related to early school dropout among students who had been judged to be
      competent or highly competent during middle school.

PMID- 9147834
TI  - Nature-nurture in the classroom: entrance age, school readiness, and learning in
      children.
AB  - The impact of entrance age on reading and mathematics achievement in 1st grade
      was examined. Methodological problems with past research were identified,
      including small size of achievement differences, failure to take background
      variables into account, and confusion of achievement levels with degree of
      learning. Using a pre-post design, growth of reading and mathematics was examined
      in younger 1st graders, older 1st graders, and older kindergarteners. Comparisons
      of background information on these groups with children who were either held out
      prior to or retained an extra year in kindergarten, produced minimal background
      differences. Results revealed that younger 1st graders made as much progress over
      the school year as did older 1st graders and made far more progress than older
      kindergarteners. Overall, findings demonstrated that, in itself, entrance age was
      not a good predictor of learning or academic risk.

PMID- 9147835
TI  - Relations among children's social goals, implicit personality theories, and
      responses to social failure.
AB  - Two studies examined children's thought patterns in relation to their responses
      to social challenge. In Study 1, 4th and 5th graders tried out for a pen pal club
      under either a performance goal (stressing the evaluative nature of the tryout)
      or a learning goal (emphasizing the potential learning opportunities). In their
      behavior and attributions following rejection, children who were focused on a
      performance goal reacted with more helplessness, whereas children given a
      learning goal displayed a more mastery-oriented response. Study 2 found that in
      response to hypothetical socially challenging situations, 4th, 5th, and 6th
      graders who believed personality was nonmalleable (entity theorists) vs.
      malleable (incremental theorists) were more likely to endorse performance goals.
      Together, these studies indicate that children's goals in social situations are
      associated with their responses to social failure and are predicted by their
      implicit theories about their personality.

PMID- 9147836
TI  - Bias in adolescents' everyday reasoning and its relationship with intellectual
      ability, personal theories, and self-serving motivation.
AB  - The author presented 60 9th- and 12th-graders with hypothetical arguments that
      contained logical fallacies. Arguments were either consistent or inconsistent
      with participants' theories. Participants rated the quality and truth of each
      argument, identified perceived strengths and weaknesses in the arguments, and
      verbally described hypothetical experiments that could lead to evidence
      falsifying the claims made in the arguments. Results indicated that intellectual
      ability, particularly verbal ability, was the best predictor of each index of
      everyday reasoning. However, neither the ability measures nor age were related to
      biases in everyday reasoning. Hierarchical multiple regression analyses showed
      that, for each reasoning variable, adolescents' personal theories accounted for
      the most variance in reasoning biases. These findings are discussed in terms of
      the roles that intellectual ability and theory-driven motivation play in everyday
      reasoning and self-serving adolescent reasoning.

PMID- 9147837
TI  - Emotion regulation in mother-child narrative co-construction: associations with
      children's narratives and adaptation.
AB  - The associations were studied between early mother-child co-construction of a
      separation-reunion narrative and children's concurrent and later (a) emotion
      narratives and (b) behavior problems. Fifty-one children and their mothers were
      observed during a co-construction task when the children were age 4 1/2. At ages
      4 1/2 and 5 1/2, children's narratives were elicited using the MacArthur Story
      Stem Battery (MSSB), and mothers completed the Child Behavior Checklist. Results
      showed that children who were more emotionally coherent during the co
      constructions had MSSB narratives that were more coherent, had more prosocial
      themes, and had fewer aggressive themes at ages 4 1/2 and 5 1/2. Moreover, such
      children had fewer behavior problems at both ages. The relations between
      narrative processes and emotion regulation are discussed.

PMID- 9147838
TI  - Developing narrative structure in parent-child reminiscing across the preschool
      years.
AB  - This study is a longitudinal exploration of relations between parents' and
      children's provision of narrative structure in joint retellings of the past and
      children's developing personal narrative skills. Fifteen White, middle-class
      families participated when children were 40 and 70 months old. At both ages,
      mothers and fathers talked separately with children about shared past events and
      uniformed experimenters elicited children's personal narratives. Whereas mothers
      and fathers did not differ in how they structured past narratives, children
      narrated differently with fathers than with mothers. Further, even at 40 months,
      girls' narratives were more contexted and evaluative than boys, but parents'
      provision of narrative structure increased similarly with daughters and sons over
      time. Children's early abilities to provide evaluative narratives was a strong
      predictor of their later abilities to provide evaluative narratives; maternal
      emphasis on evaluations also predicted children's later narrative structure.
      Parental and child influences on personal narrative skill development are
      discussed.

PMID- 9147839
TI  - Inhibition in boys with attention deficit hyperactivity disorder as indexed by
      heart rate change.
AB  - A stop signal paradigm in combination with heart rate measures were used to test
      the hypothesis of deficient inhibitory processing in boys with attention deficit
      hyperactivity disorder (ADHD). The authors measured the inhibitory process
      initiated by a stop signal by observing its success, its latency using a horse
      race model, and its impact on the timing of the heartbeat. Boys with ADHD
      performed well and showed appropriate psychophysiological changes. Inhibition
      latencies were longer in the boys with ADHD, particularly those with concurrent
      oppositional defiant disorder, than in the controls. Cardiac evidence suggested
      that greater preparation was associated with inhibition failures in controls, but
      not in the boys with ADHD. Boys with ADHD seem capable of attending carefully to
      control responses, but this control appears less effective and arguably is more
      effortful than in other boys.

PMID- 9147840
TI  - Continuity and change in children's social maladjustment: a developmental
      behavior genetic study.
AB  - Two developmental models were used to study genetic and environmental mechanisms
      underlying continuity and change in children's maladjustment. The transmission
      model assumed that successive levels of functioning were causally linked and that
      earlier experiences or prior genetic influences affected later maladjustment. The
      liability model related continuity in problem behavior to stable underlying
      environmental or genetic factors. The analyses pertained on average to 436 pairs
      of full siblings, 119 pairs of half siblings, and 122 pairs of cousins for whom
      maternal ratings of problem behaviors were available at ages 4-6, 6-8, and 8-10.
      Nonshared environmental influences appeared to be most important for changes in
      children's problem behaviors and did not have significant effects on age-to-age
      continuity. To represent the genetic and shared environmental mechanisms
      underlying stability in problem behavior, the authors preffered liability models
      without time specific effects.

PMID- 9147841
TI  - Mom and dad are at it again: adolescent perceptions of marital conflict and
      adolescent psychological distress.
AB  - In these two studies, the authors used children's perceptions of family
      relationships to examine simultaneously direct and indirect links between marital
      conflict and child adjustment. With data pertaining to 146 sixth and seventh
      graders, Study 1 supported direct and indirect effects of perceptions of marital
      conflict on internalizing behaviors, and indirect effects for externalizing
      behaviors. In Study 2, data analyzed from 451 families showed indirect effects of
      marital conflict and parent-to-child hostility, through adolescent perceptions of
      such behavior, on both current distress and distress 12 months later in 3 of 4
      models estimated. Direct and indirect effects were found for boys' concurrent
      internalizing behavior. Implications and limitations of both studies are
      discussed to address the need for a more sophisticated theoretical approach to
      examine why an association exists between marital conflict and child adjustment.

PMID- 9147842
TI  - Genetic and environmental influences on parent-son relationships: evidence for
      increasing genetic influence during adolescence.
AB  - Genetic and environmental influences on self-reported parent-child relationships
      were examined in a sample of 824 individual male twins and their parents. Cross
      sectional comparisons of twin similarity at ages 11 and 17 were undertaken to
      identify developmental changes in the contribution of genetic and environmental
      factors to family relationships. Significant genetic influences were found on
      perceptions of parent-son conflict, regard, involvement, and overall support.
      Heritabilities were significantly higher in older twins, suggesting increased
      genetic influence with age. Age differences were present primarily in the father
      son relationship. These results provide support for the proposal of S. Scarr and
      K. McCartney (1983) that the importance of active gene-environment correlations
      increases during adolescence. Older adolescents may have more choice and impact
      on the nature of the relationships they have with their parents.

PMID- 9147843
TI  - Verbal and spatial working memory in school-age children: developmental
      differences in susceptibility to interference.
AB  - The development of verbal and spatial working memory was investigated with an
      interference paradigm. Memory spans were obtained from 3 groups (8-, 10-, and 19
      year-olds) under 6 different conditions: Two primary memory tasks (1 verbal, 1
      spatial) were administered in isolation and in conjunction with 2 versions of a
      secondary task. The primary tasks required recalling a series of visually
      presented digits and recalling the locations of Xs in a series of visually
      presented grids. The secondary tasks required reporting the color of the stimuli
      as they were presented using either a verbal or a spatial response. Analyses
      revealed that all age groups showed domain-specific interference (i.e.,
      interference by a secondary task from the same domain as the primary task), but
      only the 8-year-olds also showed nonspecific interference (i.e., interference by
      a secondary task from a domain different than the primary memory task),
      suggesting that at least some executive functions do not reach adult levels of
      efficiency until approximately age 10.

PMID- 9147844
TI  - Age differences in, and consequences of, multiple- and variable-strategy use on a
      multitrial sort-recall task.
AB  - Second-, 3rd-, and 4th-grade children were given 5 sort-recall trials with
      different sets of categorizable items. The authors assessed multiple-strategy use
      on each trial and related intertrial changes in strategy use to levels of recall.
      Multiple-strategy use increased with age but was observed at all grades. Fourth
      graders who used more strategies had higher recall, with this pattern occurring
      only on later trials for 2nd and 3rd graders. Children of all ages showed
      substantial intertrial variability in using multiple strategies. Stable-strategy
      use (few strategy changes across trials) was related to high levels of recall,
      both for individual and group data, and was associated with the use of different
      numbers of strategies at different ages. Results were interpreted in light of new
      research and theory postulating that multiple- and variable-strategy use is the
      rule rather than the exception in development and that strategies do not always
      facilitate task performance (utilization deficiencies).

PMID- 9147846
TI  - [Tumor suppressor genes].
AB  - The main role of tumour suppressor genes is the inhibition of cell proliferation.
      Somatic mutations in these genes are found frequently in sporadic tumors. Germ
      line mutations in tumour suppressor genes are responsible for hereditary cancer
      syndromes. In a carrier of such a germ line mutation, a somatic mutation or loss
      of the remaining functional copy of the gene is sufficient for the complete loss
      of function of the tumour suppressor. Therefore the carriers of germ line
      mutations have a high risk of developing malignancies. Many tumour suppressor
      genes have been cloned and characterized recently and many others are intensively
      searched for. Protein products of these genes serve different cellular functions
      and many of them directly participate in the cell cycle control. The
      characterization of tumour suppressor genes is important both for the
      understanding of processes of carcinogenesis and for practical use in the
      diagnostics, prognostics and therapy of tumours.

PMID- 9147845
TI  - [Plasma apolipoproteins: their role in cardiovascular diseases and usefulness of
      their blood concentration determination. Committee of the Study of
      Apolipoproteins, Italian Heart Foundation].

PMID- 9147847
TI  - [Gene therapy of malignant tumors. Prospects of cytokine gene transfer vaccines].
AB  - Therapeutic strategies based on the insertion of cytokine genes into the genome
      of tumour cells, followed by vaccination with the resulting genetically modified,
      cytokine-producing cells, represent a new potential prospect for treatment of
      cancer patients. In this review, the concept of cytokine gene-modified cancer
      vaccines is discussed; the discussion in focused on the rationale,
      characterization, progress in the development, preclinical testing, and first
      clinical trials. An effort is made to analyse and integrate the results obtained
      in different experimental model systems to determine the needed approaches and
      directions for further research.

PMID- 9147848
TI  - [Will transfer of cytostatic drug resistance genes increase hematopoiesis
      resistance in the treatment of malignant tumors?].
AB  - The aim of aggressive antitumor chemotherapy is to kill the tumor with the
      largest possible dose of a cytotoxic drug. The maximum dose tolerated by the
      patient is limited by the toxicity to normal tissue, hematopoiesis being
      frequently the most sensitive system. Transfer of drug resistance genes to
      hematopoietic cells could protect them against chemotherapy-related toxicity and
      thus could be a way of gene therapy in cancer. Methylating and chloroethylating
      derivatives of nitrosourea are effective anticancer drugs, however, acute
      hematopoietic toxicity and late risk of leukemia are serious side effects. The
      major lesion responsible for toxic and mutagenic effects of alkylnitrosoureas is
      O6-alkylation of guanine in DNA. This lesion is specifically repaired by O6
      alkylguanine-DNA-alkyltransferase and hematopoietic cells can be protected
      against toxic and mutagenic effect of nitrosoureas by alkyltransferase gene
      transfer. Endogenous alkyltransferase in tumor tissue could be inactivated by
      administration of O6-benzylguanine, while hematopoietic cells could still be
      chemoprotected by inhibitor-resistant alkyltransferase gene transfer. This
      approach could increase the therapeutic efficacy of nitrosoureas in gene therapy
      augmented cancer treatment.

PMID- 9147849
TI  - [Expectations of gene therapy in the Czech Republic].

PMID- 9147850
TI  - [Principles of gene therapy in tumors].
AB  - Gene therapy (GT) of cancer represents one of the most promising and exciting
      innovations in contemporary medicine. Several different strategies of GT of
      cancer have been developed. In spite of the rapid methodological progress their
      exploitation encounters a variety of problems. The most pertinent are associated
      with the use of vectors for gene transfer. Nowadays, virus-based vectors are
      preferred to the physical-chemical approaches. A special position in the
      methodology of cancer GT belongs to the so-called suicide genes. The expression
      of these genes in tumour cells results in their death provided they have been
      exposed to certain, originally innocuous substances. Combination of suicide genes
      with those coding for cytokines may eventually yield a very efficient means both
      for prevention and treatment of cancer. GT is connected with a number of
      considerable scientific, organizational and ethical problems. Coping with them
      requires extraordinary effort and well-organized and deliberate international
      cooperation.

PMID- 9147851
TI  - [Human memory and its animal models].
AB  - The term memory expresses the ability of the human or animal CNS to store
      information. Memory can be classified according to different principles. Short
      term memory and long-term memory represent the basic classification. Within the
      long-term memory, a declarative and a nondeclarative form can be distinguished.
      The declarative memory provides a consciously accessible record of individual
      previous experiences. Nondeclarative memory includes motor skills, perceptual
      procedures and simple conditioned reactions. It is characteristic for
      nondeclarative knowledge, that the individual is not well aware what exactly he
      learned. Formation of the declarative memory traces requires processing in the
      hippocampus, while nondeclarative learning does not. Studies on animals suggest
      that declarative memory is stored by changes in synaptic strength at contacts
      involving NMDA receptors in the hippocampus. The ion channel associated with the
      NMDA receptor is usually blocked by Mg2-. It becomes unblocked only when the
      postsynaptic cell is depolarized, for instance during simultaneous activation of
      NMDA and nonNMDA receptors. Resulting Ca2+ influx into the postsynaptic cell
      initiates activation of second-messenger kinases followed by strengthening the
      synapses that were activated during depolarization. The molecular substrate of
      nondeclarative memory in unknown. Both forms of memory can be modelled in
      laboratory animals and analyzed experimentally. An analogy of declarative memory
      requires memory-stored cognitive maps of the outside world and lists of expected
      consequences of various actions. Motor learning can serve as a suitable model of
      complex nondeclarative (procedural) memory.

PMID- 9147852
TI  - [Cell-mediated immunity in patients with Sjogren's syndrome].
AB  - BACKGROUND: Sjogren's syndrome (SS) is considered an autoimmune
      immunopathological disease, which is characterized by disorders of humoral and
      cell-mediated immunity. The objective of the work was to assess the ratio of T
      and B lymphocytes, subpopulations of T lymphocytes and NK cells in the peripheral
      blood of patients suffering from SS. METHODS AND RESULTS: The investigated group
      was formed by 22 patients with the diagnosis of primary SS (mean age 55.7 years,
      range 39-83 years), 17 patients with the diagnosis of secondary SS (mean age 60.5
      years, range 45-79 years). The ration of CD3-, CD4-, CD8-, CD19-, CD5-, CD25- HLA
      DR- cells in full blood was assessed by the monoclonal antibody technique of
      direct immunofluorescence, using evaluation by means of a flow cytometer. The
      results were compared by statistical methods with a control group of blood donors
      using Student's t-test, A relative increase of the ratio of CD3- T lymphocytes
      was revealed in patients with primary SS (75.3 +/- 17.9 %, p = 0.380) and
      secondary SS (73.7 +/- 11.8, p = 0.326), as compared with controls (65.3 +/-
      10.3%). The absolute number of the subpopulation of suppressor helper inducer
      CD4+ T lymphocytes was markedly lower in patients with primary SS (0.056 +/- 0.27
      - 10(9)/l, p = 0.0154), as compared with controls (0.81 +/- 0.27, 10(9)/l. The
      relative number of suppressor cytotoxic CD8- T lymphocytes was significantly
      higher in patients with primary SS (33.7 +/- 15.0%, p = 0.0001 and secondary SS
      (30.5 +/- 11.0%, p = 0.0002), as compared with controls (17.2 +/- 6.0%). The
      absolute number of inhibitory cytotoxic T lymphocytes was significantly higher in
      patients with primary SS (0.47 +/- 0.3. 10(9)/1, p = 0.0084) and patients with
      secondary SS (0.48 +/- 0.3, 10(9)/l, p = 0.0072). The relative number of CD57+ NK
      cells was significantly higher in patients with primary SS (21.1 +/- 11.0%, p =
      0.0001) and secondary SS (19.3 +/- 11.7%, p = 0.0023). The absolute number of NK
      cells was significantly higher in patients with primary SS (0.28 +/- 0.20,
      10(9)/l, p = 0.0025 and in patients with secondary SS (0.31 +/- 0.23, 10(9)/l, p
      = 0.01). CONCLUSIONS: The revealed statistically significant increases in the
      number of T lymphocytes in patients with Sjogren's syndrome is probably caused by
      a significant increase of the subpopulation of CD8+ suppressor cytotoxic T
      lymphocytes. The latter probably overlap with the population of NK cells. These
      immunological abnormalities are even more marked in patients with primary
      Sjogren's syndrome due to the decrease of the absolute number of CD4+ helper
      inducer T lymphocytes.

PMID- 9147853
TI  - [Valve replacement in congenital aortic stenosis].
AB  - BACKGROUND: Hemodynamically significant congenital aortic stenosis is usually
      surgically solved by valvotomy, infrequently aortic valve replacement is
      necessary. The aim of this retrospective study (period 1979-1995) is to find
      reasons for valve replacement, frequency of these procedures and early and long
      term results after aortic valve replacement for congenital aortic stenosis.
      METHODS AND RESULTS: Congenital aortic stenosis was solved by aortic valvotomy in
      82 patients and by aortic valve replacement in 18 patients. Aortic valve
      replacement was performed 6x for congenital valvar aortic stenosis with mean
      aortic gradient 53.7 +/- 13.9 mm Hg and aortic valve area 0.42 +/- 0.04 cm2/m2
      and 4x for valvar and subvalvar stenosis with mean aortic gradient 87.0 +/- 31.3
      mm Hg, valve area 0.45 +/- 0.03 cm2/m2 and associated regurgitation 44.7 +/-
      25.6%. In the remaining 8 patients aortic valve replacement was performed as
      reoperation after aortic valvotomy (after 20 +/- 8.4 years). In this group mean
      aortic gradient was only 32.2 +/- 13.8 mm Hg but regurgitation was 54.0 +/-
      15.8%. Infective endocarditis occurred in 8 patients (44.5%) preoperatively.
      There were two hospital deaths (sudden death and multiorgan failure) and one
      death 3 years after operation (prosthetic endocarditis). Remaining 15 patients
      are in very good condition (NYHA I.-II.) 1-13 years after aortic valve
      replacement. CONCLUSIONS: Severely calcified aortic valve, endocarditis and
      associated incompetence are indications for valve replacement in patients with
      congenital aortic valve disease. Prevention of infective endocarditis is
      necessary pre and postoperatively, too. Long-term results after valve replacement
      for aortic valve stenosis are very good.

PMID- 9147854
TI  - [Review of 105 cases of isolation of Rhodococcus equi in humans].
AB  - BACKGROUND: Rhodococcus equi (formerly Corynebacterium) has been long considered
      an exclusively zoopathogenic microbe causing mainly granulomatous pneumonias and
      lung abscesses in young foals. The aim of this paper was to analyse substantial
      features of R, equi infections hitherto reported in man. METHODS AND RESULTS:
      MEDLINE database was searched for relevant reports. When the original source was
      not obtained the data from reviews were employed. Together, 105 cases of R, equi
      infection in man were reported. Median age was 35 years with a range from 9
      months to 83 years. The male: female ratio was 3.3. Lungs were involved in 72
      cases (69%), extrapulmonary abscesses as the only symptom of infection were
      described in 9 cases, septic state in 7 cases. Clinical outcome was known in 98
      cases, being fatal in 41 (42%). Therapy was mentioned in 70 reports, the most
      often used drugs being erythromycin (30 cases, 12 deaths), rifampicin (19 cases,
      7 deaths) and vancomycin (18 cases, 6 deaths). R. equi was isolated from the
      sputum of 69% patients with the pulmonary involvement. Blood cultures were
      positive in 35% of cases. Out of total, 49% persons were HIV positive. Median age
      for HIV positive patients was 32 years with a range from 18 to 71 years, for HIV
      negative patients 52 years with a range from 9 months to 83 years. There were 97%
      males in the HIV positive group in contrast to 59% in the HIV negative group (p <
      0.01). Lungs were involved in 90% of HIV positive and 48% of HIV negative cases
      (p < 0.01). Extrapulmonary abscesses as the only sign of infection were seen in
      2% of HIV positive persons and in 15% of HIV negative ones (p < 0.05). Outcome
      was fatal for 60% of the HIV positive hosts and for 28% of the HIV negative
      individuals (p < 0.01). R. equi was isolated from the sputum of 80% pneumonic HIV
      positive patients and of 50% of pneumonic patients without HIV infection (p <
      0.05). R. equi was detected in the blood of 67% of HIV positive patients and of
      33% of HIV negative ones (p < 0.01). CONCLUSIONS: The analysis of published
      reports shows that whereas R. equi causes mainly pneumonia in persons with HIV
      infection, in HIV negative individuals extrapulmonary manifestations slightly
      prevail, most often abscesses, sepsis, eye involvement and wound infections.

PMID- 9147855
TI  - [Growth and puberty in children after treatment of acute lymphoblastic leukemia].
AB  - BACKGROUND: Growth retardation and other endocrine abnormalities were recognized
      as sequelae of therapy of acute lymphoblastic leukemia (ALL), especially when
      chemotherapy was combined with cranial irradiation. The aim of our study was to
      establish growth and pubertal development in the group of children who had been
      previously successfully treated for ALL. METHODS AND RESULTS: 58 children (30 F,
      28 M, age 8-18 y.) in complete initial remission lasting 4-15 y. (m 8 y.) after
      standard antileukemic therapy (including cranial irradiation) completed 2-9 y.
      ago (m 3 including y.) were studied. Standard deviation score (SDS) of standing
      height (SH) to chronological age (CA) and to genetic target height (GTH), index
      of body proportionality and timing of puberty were followed up. The final height
      attained 21 girls and 3 boys. The height of the boys differed neither from the
      average for our men, nor from their GTH. Girls: SH 148 cm-169 cm, SH of 7 girls >
      or = -1.5 SDS, 8 girls > or = -1.5 SDS to their GTH. The final height didn't
      reach yet 23 boys and 9 girls. Their SH to CA as well as SH to GTH didn't
      substantially differ from average. Index of body proportionality > or = 1.5 SDS
      in 12/30 girls and 6/28 boys. Menarche was already reached in 25 girls in age
      ranging from 10-15 y. (mean 11.3 y.), what was less than average for our
      population (13.3 y.). CONCLUSION: Even the height of prepubertal children under
      study didn't differ from average, the final height of girls (boys could not be
      evaluated because of small numbers) was significantly lower as could be expected.
      We suppose the early ending of puberty as a contributing factor of short stature
      in girls. Clear tendency to obesity especially among older girls was observed.
      Children who underwent antileukemic therapy deserve careful endocrinological
      follow-up.

PMID- 9147856
TI  - [Effect of clodronate in patients with multiple myeloma. Evaluation of specific
      markers of bone resorption].
AB  - BACKGROUND: In adjuvant therapy of patients with multiple myeloma among others
      anti-absorption properties of bisphosphonates are used. The objective of the
      present investigation was to evaluate the effect of long-term oral treatment
      route clodronate on the bone metabolism in this condition. As markers of bone
      reabsorption, assessment of pyridinoline and deoxypyridinoline in urine was used.
      METHODS AND RESULTS: We investigated in an open clinical trial 22 patients with
      multiple myeloma with bone changes confirmed on X-ray who had a normal calcium
      and creatinine serum concentration: the control group (A) comprised 13 patients
      (mean age 59 years, range 38-74 years), the experimental group (B) 9 patients
      (mean age 54 years, range 42-60 years). The patients in both groups were treated
      by chemotherapy, to group B concurrently clodronate 3 x 800 mg was administered
      by the oral route. No statistically significant differences were found between
      the two groups during the mean follow up period after assessment of the diagnosis
      (27 vs. 40 months) nor in the clinical stage of the disease. After intervals of
      0, 3 and 12 months the excretion of pyridinoline and deoxypyridinoline in urine
      was assessed by liquid chromatography. At the same time also other parameters of
      osteoresorption were assessed (urinary calcium and hydroxyproline excretion). At
      the onset of the investigation the pyridinoline and deoxypyridinoline excretion
      in groups A and B did not differ statistically (pyr; 120.63 +/- 23.76 vs. 136.23
      +/- 22.13 mumol/mmol creatinine. d-pyr: 19.61 +/- 3.65 vs. 22.76 +/- 5.40
      mumol/mmol creatinine). After three months in group B a statistically significant
      drop of excretion of both metabolites was recorded (pyr. to 84.11 +/- 38.67
      mumol/mmol creatinine, d-pyr. to 15.23 +/- 6.10 mumol/mmol creatinine). Their
      significantly reduced excretion persisted also after one year (pyr. 85.52 +/-
      60.96 mumol/mmol creatinine, d-pyr. 12.6 +/- 6.56 mumol/mmol creatinine).
      CONCLUSIONS: Using specific markers, pyridinoline and deoxypyridinoline, the
      authors proved the favourable effect of long-term administration of clodronate on
      the bone metabolism in patients with multiple myeloma.

PMID- 9147857
TI  - More on controlling intrauterine pressure during hysteroscopic surgery.

PMID- 9147859
TI  - Coding and reimbursement for obstetric-gynecologic services.

PMID- 9147858
TI  - Assessments of laparoscopic-assisted vaginal hysterectomy.
AB  - STUDY OBJECTIVE: To assess laparoscopic-assisted vaginal hysterectomy (LAVH) by
      operative intervention, recovery time, morbidity, and patient satisfaction.
      DESIGN: A retrospective, cohort study conducted from 1990 to 1992. SETTING: Two
      community hospitals. PATIENTS: One hundred seventy-eight women thought to require
      abdominal hysterectomy. INTERVENTIONS: Three gynecologic surgeons performed the
      LAVHs. For each case, several features were tabulated and final pathologic
      diagnoses were recorded. Patient satisfaction was measured by survey. Data were
      divided into three time epochs, early, middle, and late, and the outcomes were
      compared. We also measured the impact of LAVH on th number of abdominal
      hysterectomies. MEASUREMENTS AND MAIN RESULTS: The mean operative time was 119.4
      minutes (SD 34.1 min). The mean uterine weight was 153.4 g (SD 100.3 g), and only
      29 patients (16.3%) had no pathologic condition. The mean length of hospital stay
      was 1.3 days (SD 0.92 days) and diminished over the 2 years of the study. Mean
      hemoglobin decrement was 2.6 g (SD 1.2 g). Thirteen patients had complications
      other than febrile morbidity and seven had febrile morbidity, for an overall
      complication rate of 11.2% There were no significant differences in blood loss,
      complication rate, uterine weight, or operative time among the three epochs. One
      hundred thirty-two patients (73.0%) responded to the survey and expressed high
      satisfaction. The proportion of hysterectomies performed abdominally diminished
      over the course of the study. CONCLUSIONS: Morbidity associatd with LAVH was
      similar to that reported for vaginal hysterectomy. The lack of controls precludes
      knowing whether patient satisfaction was related to type of procedure.
      Randomized, controlled trials of women not considered candidates for vaginal
      hysterectomy are necessary to assess this procedure.

PMID- 9147860
TI  - Allen-Masters syndrome is caused by trauma, not by endometriosis.

PMID- 9147861
TI  - Cost-benefit analysis of laparoscopic versus laparotomy salpingo-oophorectomy for
      benign tubo-ovarian disease.
AB  - STUDY OBJECTIVE: To compare laparoscopy and laparotomy adnexectomy with respect
      to operating time, complications, length of hospitalization, convalescence,
      effectiveness, and surgical and equipment cost. DESIGN: A comparison of 30
      consecutive patients undergoing laparoscopic adnexectomy from January 1990 to
      July 1991, and 27 consecutive patients who underwent adnexectomy by laparotomy
      from January 1985 to December 1990. SETTING: Private practice of one surgeon
      (GAV), and Department of Obstetrics and Gynecology, Lawson Research Institute,
      St. Joseph's Health Care Center, London, Ontario, Canada. PATIENTS: All patients
      had had a hysterectomy with preservation of at least one adnexa. The indications
      for adnexectomy were chronic pelvic pain or adnexal mass less than 6 cm diameter,
      with benign characteristics defined by sonography and tumor markers.
      INTERVENTIONS: Laparoscopic adnexectomy was performed by three-puncture technique
      with bipolar coagulation and endoloop ligation of the pedicle. Dissection and
      resection were performed with the carbon dioxide laser or scissors. RESULTS:
      Differences were noted between laparoscopy and laparotomy (mean +/- SD) in
      operating time (90 +/- 40 vs 65 + 20 min, p < 0.01), complications (11% vs 18.5%,
      p < 0.05), effectiveness (72% vs 72%), length of hospitalization (1.7 +/- 1.0 vs
      7.1 +/- 1.2 days, p < 0.05), convalescence (2.2 +/- 1.7 vs 9.5 +/- 5.2 wks, p <
      0.05), surgical cost ($1603 vs $5158), and equipment cost ($198,048 vs $17,345).
      CONCLUSIONS: Operating time, complications, safety, efficiency, and effectiveness
      were comparable for the two procedures. Markedly reduced hospitalization in the
      laparoscopy group resulted in a mean saving per patient of $3555. These women
      also had shorter convalescence and earlier return to normal activities and
      employment. The cost of laparoscopic equipment appears prohibitive, but it pays
      for itself after 50 surgical procedures.

PMID- 9147862
TI  - The case report by Nezhat et al (2(1):83-86, 1994)

PMID- 9147863
TI  - Endoscopic removal of pathologic specimens is always a challenge.

PMID- 9147864
TI  - Dr. Griffin's special article on CPT coding, RBRVS, and reimbursement issues.

PMID- 9147865
TI  - "Laparoscopic treatment of an interstitial pregnancy" (1995;2(2):219-222)

PMID- 9147866
TI  - Aspects of the mechanisms of action of biguanides on trophozoites and cysts of
      Acanthamoeba castellanii.
AB  - A non-radioactive method was used to investigate the uptake by Acanthamoeba
      castellanii of chlorhexidine diacetate (CHA) and polyhexamethylene biguanide
      (PHMD). Based on the Giles et al. (1974) hypothesis, the uptake of CHA by
      trophozoites appeared to be of the L3 pattern whereas that of cysts was C2.
      Unlike CHA, trophozoites took up PHMB with an L2 pattern at low concentrations
      followed by a C-type pattern at higher concentrations, the uptake by cysts was
      found to be of the C2 pattern with a plateau effect at high concentrations. A
      diphasic leakage effect was found in trophozoites whereas a relatively low peak
      of maximal leakage occurred from cysts treated with high biocide concentrations.
      The amount of pentose release depended on the formulation ingredients. No
      correlation between pentose leakage and trophozoicidal or cysticidal activity was
      found.

PMID- 9147867
TI  - Viability of Cryptosporidium parvum during ensilage of perennial ryegrass.
AB  - The survival of Cryptosporidium parvum during ensilage of perennial ryegrass was
      examined in laboratory silos with herbage prepared in one of three different
      ways; either untreated, inoculated with a strain of Lactobacillus plantarum or by
      direct acidification with formic acid. The pH values of all silages initially
      fell below 4.5, but only formic acid-treated silage remained stable at less than
      pH 4 after 106 d, with the pH of the untreated and inoculant-treated silages
      rising to above 6. The formic acid-treated silage had a high lactic acid
      concentration (109 g kg-1 dry matter (DM)) and low concentrations of propionic
      and butyric acids after 106 d. However, the untreated and inoculant-treated
      silages showed an inverse relationship, with low lactic acid concentrations and
      high concentrations of acetic, propionic and butyric acids. These silages also
      contained ammonia-N concentrations in excess of 9 g kg-1 DM. In terms of the
      viability of Cryptosporidium parvum oocysts very few differences were seen after
      14 d of ensilage with ca 50% remaining viable, irrespective of treatment and
      total numbers had declined from the initial level of 5.9 x 10(4) to 1 x 10(4) g(
      1) fresh matter. Total oocyst numbers remained approximately the same until the
      end of the ensiling period, with the percentage of viable oocysts declining to
      46, 41 and 32% respectively for formic acid, inoculant and untreated silages. The
      results are discussed in terms of changes occurring during the silage
      fermentation, in particular the products which may influence the survival of
      Cryptosporidium and implications for agricultural practice and the health of
      silage fed livestock.

PMID- 9147868
TI  - [Correction to the airflow measurement in the presence of a leak between the
      trachea and endotracheal tube].
AB  - PURPOSE: To estimate the leak between the endotracheal tube and the trachea in
      newborns in order to compensate for errors in airflow measurement and to monitor
      mechanical variables from pressure and flow signals. METHODS: Assuming that the
      leak resistance (Rf) is constant during a respiratory cycle, the resistive
      properties of the endotracheal tube were evaluated. The method was validated in
      the intensive care unit with a mechanical test lung and assessed on recordings of
      three newborns during mechanical ventilation for RDS. We have used a least
      squares method for the estimation of positive end expiratory pressure (PEEP) on
      both newborns and simulated data. RESULTS: Direct measurements of simulated leak
      resistances on the mechanical lung are in agreement with our estimation of leak
      resistances. In newborns, the success of flow correction is evidenced on end
      inspiratory pauses: corrected flow drops to zero while raw data show a constant
      nonzero flow. On the simulated lung, the PEEP underestimation with uncorrected
      flow ranges from 10 to 20 cm H20 while the corresponding, underestimation with
      corrected flow is less than 2 cm H2O. In newborns, the flow correction shifts the
      estimated PEEP from negative values (-0.3 +/- 1.3 cm H2O before correction) to
      positive values (3.6 +/- 0.7 cm H2O after correction) higher than the imposed
      PEEP (2 cm H2O). CONCLUSIONS: The efficiency of this simple method has been
      demonstrated. It could be used successfully on adult patients, as there will not
      be flow correction in the absence of leaks.

PMID- 9147869
TI  - Primed IN situ labelling (PRINS) as a rational procedure for identification of
      marker chromosomes using a panel of primers differentially tagging the human
      chromosomes.
AB  - PRimed IN Situ labelling (PRINS) is a highly specific and sensitive technique for
      detecting DNA sequences on human chromosomes in situ. PRINS is currently being
      introduced for research and routine analysis in clinical and cancer genetics. In
      this paper, we report a rational PRINS procedure for the rapid identification of
      marker chromosomes. Using this method it is possible to test a sample from a
      patient with up to eight different primers simultaneously on one slide. We have
      synthesized oligonucleotide primers that can differentially tag the human
      chromosomes, and with the protocol presented in this report we are able to
      identify the chromosomal origin of a marker chromosome within 2 hours.

PMID- 9147870
TI  - Abnormal extracellular matrix in Ehlers-Danlos syndrome type IV due to the
      substitution of glycine 934 by glutamic acid in the triple helical domain of type
      III collagen.
AB  - A unique substitution of glycine 934 by glutamic acid in the triple helical
      domain of type III collagen was identified in a proband with Ehlers-Danlos
      syndrome type IV. The substitution was due to the transition of G 3302 to A in
      alpha 1(III) cDNA which is encoded by exon 46 of COL3A1. It resulted in a severe
      deficiency of type III collagen in fibroblast cultures and dermis. Dilatation of
      the endoplasmic reticulum of the dermal fibroblasts was probably due to the
      failure of these cells to secrete type III collagen molecules containing one or
      more mutant alpha 1(III) chains. The dermal collagen fibrils were narrow, but
      their constituent type III collagen molecules contained predominantly normal
      alpha 1(III) chains. As a results, the major effect of the substitution of
      glycine 934 by glutamic acid was to severely reduce the amount of normal type III
      collagen available for the formation of heterotypic collagen fibrils in the
      extracellular matrix.

PMID- 9147871
TI  - Craniofacial morphology of the tricho-dento-osseous syndrome.
AB  - Tricho-dento-osseous syndrome (TDO) is characterized by abnormal bone, hair, and
      tooth morphology. However, the reported craniofacial abnormalities are not well
      characterized. The purpose of this study was to compare the craniofacial
      parameters of 25 subjects affected with TDO (A) with those of 15 unaffected
      relatives (U). Standardized lateral cephalograms were traced and digitized. Each
      subject's data were compared by age and sex to cephalometric standards (Bolton,
      Behrents); severity was scored by standard deviations from the standard mean, and
      then grouped into A vs. U. All cephalograms were evaluated for frontal sinuses,
      mastoid pneumatization, diploe, and bone density, and cranial thickness was
      measured. Cranial base length (SN; NBa), cranial base angle (BaSN), and
      mandibular body length (GoPg) were greater in A than in U (p < or = 0.05). Both
      groups had longer total and lower facial heights (NMe; ANSMe) compared with
      normal standards. Frontal sinuses, mastoid pneumatization and diploe were visible
      less often in A than in U (p < or = 0.05). Parietal bone and bone at lambda was
      significantly thicker (p < or = 0.05) in A than in U. Variability was substantial
      in many measures in both A and U. The major TDO craniofacial features involve the
      cranial base, mandibular body length, absence of visible pneumatized mastoids,
      frontal sinuses and diploe, and thicker cranial bone.

PMID- 9147872
TI  - Recombination between the postulated CCD/MHE/MHS locus and RYR1 gene markers.
AB  - Malignant hyperthermia (MH) susceptibility is considered a subclinical myopathy
      or a pharmacogenetic trait, and is believed to be closely associated with central
      core disease (CCD). Data support the notion that MH susceptibility is
      heterogeneous, with the ryanodine receptor I (RYR1) locus on chromosome 19 being
      one locus harboring a gene that can cause MH susceptibility. The gene for CCD is
      believed to reside in the locus on chromosome 19. In the family presented here, a
      girl has CCD, and several close relatives are MH susceptible (MHS). DNA studies
      conducted on available family members uncovered recombination between the MH
      susceptibility locus and RYR1 markers. Consequently, if one postulates that the
      CCD gene in this family resides in the same locus as the MH susceptibility gene,
      an additional CCD locus different from the RYR1 locus must also be postulated.

PMID- 9147873
TI  - The apolipoprotein E gene in Binswanger's disease and vascular dementia.
AB  - We investigated the polymorphism of the apolipoprotein E (ApoE) gene using a PCR
      RFLP method in patients with Binswanger's disease (BD), non-BD vascular dementia,
      or Alzheimer's disease (AD). The frequency of the epsilon 4 allele of the ApoE
      (ApoE4) in BD patients and non-BD vascular dementia patients did not differ from
      that observed in the nondemented elderly controls, but it was significantly lower
      than the frequency in AD patients. These results and other recent observations
      suggest that one or more factors other than the ApoE gene contribute to the
      pathogenesis of dementia in BD and non-BD vascular dementia.

PMID- 9147874
TI  - Outcomes and process in genetic counselling.
AB  - Although it may be simple to evaluate some elements of clinical genetics, it is
      difficult to evaluate genetic counselling. We review previous studies of the
      outcomes of genetic counselling; although the methods used may be valid in
      research studies, there are practical and ethical difficulties in applying them
      to the measurement of clinical effectiveness in standard practice. No simple
      measures of outcomes would be suitable. Research evidence will be helpful in
      deciding what services it is appropriate to offer, and the quality of a service
      can then be assured by assessing the quality of the clinical process in three
      ways: 1) adherence to agreed protocols and standards of care; 2) peer review and
      audit of clinical activity; and 3) ongoing review of the satisfaction of clients
      and referring physicians with the service. The assessment of client satisfaction
      will need to be a sophisticated form of retrospective satisfaction with the
      service provided, and such a scheme has yet to be fully developed.

PMID- 9147875
TI  - A history of miscarriages and mild prognathism as possible mode of presentation
      of mosaic trisomy 18 in women.
AB  - A 22-year-old woman seeking medical assistance for hypofertility after two
      miscarriages had very slight anomalies: mild macrogenia and prognathism, and
      temporal depilation. Peripheral lymphocytes and fibroblastic karyotypes disclosed
      the tenth published case of low-level mosaicism for trisomy 18 with normal
      intelligence. Subfertility is frequently observed among these patients. As women
      with this anomaly are at risk of trisomy 18 pregnancies and as five cases have
      been reported recently, this particular chromosomal anomaly may not be so
      exceptional and should be investigated in cases of hypofertility.

PMID- 9147876
TI  - Partial deletion of the long arm of chromosome 11: ten Japanese children.
AB  - The clinical features of partial deletion 11q were correlated with the size of
      the deleted region. Ten Japanese children with partial deletion of 11q were
      investigated. They were divided into three groups. Three patients in the first
      group had interstitial deletions and preserved subband q24.1. Six patients in the
      second group demonstrated terminal deletion of 11q including subband q24.1, with
      typical features of 11q- syndrome (Jacobsen syndrome). The third group included
      only one patient, who had terminal deletion of 11q without characteristics of
      typical 11q- syndrome. Prominent features of patients in the first group included
      severe mental and motor developmental delay, seizures, cleft lip and palate, and
      ophthalmological findings. Patients in the second group showed mild to moderate
      developmental delays without deterioration. Abnormalities in neuroimages, high
      intensity in the cerebral white matter in T2-weighted magnetic resonance (MR)
      images, and recurrent infections were not observed after the age of 7 years. The
      subject in the third group, with the smallest amount of deleted chromosome, did
      not show developmental delays, suggesting that some unknown genes related to
      developmental delays may be located adjacent to subband q24.1. Variation in the
      deleted parts of 11q resulted in different clinical features in each group.

PMID- 9147877
TI  - Fanconi anemia complementation group E: clinical and cytogenetic data of the
      first patient.
AB  - The clinical and cytogenetic data of the first patient proven to belong to the
      fifth Fanconi anemia complementation group are described. The Turkish boy
      presented with psychomotoric retardation, growth retardation, retarded bone age,
      brachycephaly, hypotelorism, epicanthus, syndactyly, brachydactyly, renal
      dystopia, and cryptorchism. In addition, an asymmetrical skeletal anomaly was
      seen with a double distal phalanx of the left thumb and hypoplasia of the right
      thumb. Typical hematological features of the disorder developed, at the age of
      2.5 years, about 1 year after diagnosis. Cytogenetic studies confirmed the
      clinical diagnosis and revealed a spontaneous chromosomal instability and
      hypersensitivity to the cross-linking agents diepoxybutane and Trenimon. The
      findings in the patient, who is considered to be the standard for the fifth
      Fanconi anemia complementation group, are compared with data reported for other
      patients affected with Fanconi anemia.

PMID- 9147878
TI  - APC intragenic haplotypes in familial adenomatous polyposis.
AB  - Genetic epidemiological studies are useful for the knowledge of the association
      of markers and genes involved in diseases. In the present work, we studied the
      frequency of four adenomatous polyposis coli intragenic RFLP markers often used
      in risk evaluation in a population of 10 familial adenomatous polyposis patients
      from 10 unrelated Portuguese familial adenomatous polyposis families not sharing
      the same mutation, and in a population of 55 unrelated healthy Portuguese
      volunteers. We compared the frequency obtained to normal and affected populations
      and to results already reported in other populations. We observed allelic
      frequencies for the Portuguese population that agree with the published ones. The
      intragenic polymorphisms show strong gametic disequilibrium suggesting little
      recombination between them. We observed haplotype frequencies significantly
      different in patients and controls. The gametic disequilibrium may be due to a
      common founder for a proportion of apparently unrelated probands.

PMID- 9147879
TI  - Rett syndrome in northern Tuscany (Italy): family tree studies.
AB  - Four cases of Rett syndrome were ascertained among 19,060 girls born between 1978
      and 1990 in a small, defined area of Northern Tuscany (Italy) (prevalence rate of
      2.1 per 10,000). A fifth girl with a reported clinical picture of Rett syndrome,
      born in 1978 and deceased at age 13, was also found. One of the four Rett
      syndrome cases had a healthy female dizygote twin. Family tree studies going back
      as far as the 17th century were performed. A number of common ancestors were
      found in different generations leading to a single family tree encompassing all
      four Rett syndrome cases. In addition, a Rett girl with preserved speech, born in
      1974, was found as part of this family tree. These observations confirm the role
      of genetic factors in the etiology of Rett syndrome and support the hypothesis
      that Rett syndrome is a clinically variable phenotype.

PMID- 9147880
TI  - Further evidence of genetic heterogeneity in hereditary hydronephrosis.
AB  - Hereditary hydronephrosis is a rare condition but several families are described
      in the literature. The inheritance pattern is autosomal dominant (McKusick number
      143400) but the exact aetiology of the hydronephrosis is not clear. However,
      linkage with the HLA region on chromosome six has been shown previously. We
      report a family not showing linkage to this region, giving further evidence of
      genetic heterogeneity in this condition.

PMID- 9147881
TI  - Silver-Russell syndrome and exclusion of uniparental disomy.
AB  - Recently, maternal uniparental disomy for the entire chromosome 7 was described
      in three of 25 Silver-Russell syndrome sporadic cases, yet the etiology of the
      remaining cases is unclear. Two cases with Silver-Russell syndrome and a balanced
      translocation involving the 17q25 had been reported. We looked for evidence of
      genomic imprinting due to uniparental disomy 17 in seven patients with sporadic
      Silver-Russell syndrome and their parents. Additionally, chromosomes 7, 8, 11 and
      20 were studied. Uniparental disomy was ruled out for all these chromosomes in
      six of seven families; one family was informative only for chromosome 17. Not
      withstanding our negative results, it is still possible that uniparental disomy
      plays a part in this syndrome. A mutation in a Mendelian gene in 17q25 could also
      account for the Silver-Russell syndrome etiology.

PMID- 9147882
TI  - A new autosomal recessive syndrome of pachygyria.
AB  - Pachygyria is a rare development disorder resulting from impaired neuronal
      migration. Usually, it is a sporadic phenomenon, but rare dominant or autosomal
      recessive syndromes are known. This report describes a family in which the
      parents are first cousins and three of the siblings suffer from moderate mental
      retardation, pachygyria and strabismus. It is suggested that this is a distinct
      type of autosomal recessive pachygyria.

PMID- 9147883
TI  - Tri-amelia and phocomelia with multiple malformations resembling Roberts syndrome
      in a fetus: is it a variant or a new syndrome?
AB  - Roberts-SC phocomelia syndrome is a rare autosomal recessive disorder
      characterized by morphological anomalies such as limb defects and midfacial
      clefting, and by premature centromeric division in chromosomal study. Although it
      has been regarded as a single genetic entity and includes various morphologic
      defects, babies are being reported nowadays with severe facial defects, tetra
      amelia, and pulmonary abnormality, yet with normal chromosomal findings. We have
      added a case resembling Roberts syndrome with various congenital anomalies. A
      gestation with a fetus was terminated at 24 weeks of gestational age because of
      multiple fetal anomalies. Postmortem examination revealed a severe mid-facial
      cleft, tri-amelia and phocomelia, multiple encephaloceles, protruding and
      hypoteloric eyes, low-set ears, atrial septal defect of ostium secundum type,
      patent ductus arteriosus, bilateral two-lobed lungs with incomplete lobation,
      multiple visceral anomalies, a penis without scrotum, abnormal dermoglyphics, and
      absence of nipples.

PMID- 9147884
TI  - Congenital scalp defect, distal limb reduction anomalies, right spastic
      hemiplegia and hypoplasia of the left arteria cerebri media. Further evidence
      that interruption of early embryonic blood supply may result in Adams-Oliver
      (plus) syndrome.
AB  - In this report we describe a male patient with the interesting combination of a
      large congenital scalp defect, distal limb reduction anomalies, right spastic
      hemiplegia and hypoplasia of the left arteria cerebri media. Follow-up data from
      birth up to the age of 18 years revealed positive evolution with low to normal
      intelligence. The findings in the present patient, i.e. an Adams-Oliver syndrome
      associated with a severe neurological deficit, are best explained as resulting
      from interruption of the early embryonic blood supply.

PMID- 9147885
TI  - Respiratory complications of Ehlers-Danlos syndrome type IV.
AB  - Pulmonary complications are described in a case of Ehlers-Danlos syndrome type
      IV, established by studies of collagen biosynthesis. At age 20.5 years the
      patient, who had previously suffered a spontaneous colonic perforation, developed
      intermittent recurrent hemoptysis and had a spontaneous hemopneumothorax. At
      presentation, imaging studies revealed multiple scattered cavitary lesions in
      both lungs. On separate occasions large parenchymal cysts ensued and subsequently
      regressed. Reviews of other reported patients indicate that pulmonary
      complications do occur in patients with Ehlers-Danlos syndrome type IV but have
      not resulted directly in patient mortality.

PMID- 9147886
TI  - Unusual segregation of t(11;22) resulting from crossing-over followed by 3:1
      disjunction at meiosis I.
AB  - Reciprocal translocation t(11;22)(q23;q11) is of particular interest because the
      unbalanced offspring of the translocation carriers usually present with a
      supernumerary derivative chromosome 22. This common unbalanced karyotype is the
      result of 3:1 chromosome segregation during meiosis. We report the third case of
      a rare segregation pattern of a paternal 11;22 translocation. The proband's
      karyotype revealed the presence of a der(11) and two copies of a der(22), i.e.
      47,XX,t(11;22)(q23;q11),+der(22) t(11;22)pat. The karyotype is the result of
      paternal 3:1 segregation after crossing-over involving the derived and the normal
      chromosome 22, as revealed by chromosome polymorphism analysis. Contrary to the
      preferential maternal, transmission of this common unbalanced translocation, the
      data from the literature, including our case, may suggest preferential paternal
      transmission of this rare type of unbalanced translocation.

PMID- 9147887
TI  - Partial deletion of 18p and partial duplication of 18q caused by a paternal
      pericentric inversion.
AB  - Here we report on a boy with both a partial deletion of chromosome 18p and a
      partial duplication of chromosome 18q, caused by a paternal pericentric inversion
      (46,XY,rec(18),dup q,inv(18)(p11.2q21.1)pat). The findings in the patient are
      compared to those in the literature. The symptoms in the described patient can be
      explained for the major part by the 18p- and 18q+ syndromes separately. A
      specific 18p-/18q+ syndrome cannot be clearly delineated yet. Inspiratory stridor
      is a symptom that has not been described before in either 18p- or 18q+, but has
      been found twice before in patients with the combined 18p-/18q+ syndrome.

PMID- 9147888
TI  - Identification of a double mutation in the low-density lipoprotein receptor gene
      causing familial hypercholesterolemia.

PMID- 9147889
TI  - Frequent intragenic polymorphism in the 3' untranslated region of the
      lissencephaly gene 1 (LIS-1).

PMID- 9147890
TI  - Short sequence repeats in intron 2 of the insulin receptor gene among black and
      white South Africans.

PMID- 9147891
TI  - Dinucleotide repeat polymorphisms at D9S171 and D9S741 are identical.

PMID- 9147892
TI  - A new silent C to T polymorphism in the exon 3 of the oxytocin receptor gene.

PMID- 9147893
TI  - High incidence of pre-excitation syndrome in Japanese families with Leber's
      hereditary optic neuropathy.
AB  - Cardiac conduction abnormalities have been reported in families with Leber's
      hereditary optic neuropathy (LHON). The pre-excitation syndrome Wolff-Parkinson
      White syndrome or Lown-Ganong-Levine syndrome, is reportedly common in Finns with
      LHON, being seen in 14 (9%) of the 163 individuals with mitochondrial DNA (mtDNA)
      mutations. While this syndrome is thought to be rare in other ethnic groups with
      LHON, the present study of 35 Japanese LHON families confirmed that it is also
      relatively common among Japanese families, being seen in 5 (8%) of the 63
      individuals with mtDNA mutations. It remains to be determined whether the high
      incidence of the pre-excitation syndrome in Finnish and Japanese LHON families is
      due to a particular genetic composition of ethnic groups such as in Finland and
      in Japan, or only to a reporting bias.

PMID- 9147894
TI  - Terminal deletion of the long arm of chromosome 4 in a mother and two sons.
AB  - Deletion of chromosome 4q31-->pter has been characterized as a distinctive
      malformation syndrome. We report a mother and two sons with deletion of the long
      arm (q) of chromosome 4 del(4)(q34.2).

PMID- 9147895
TI  - Insertion/deletion polymorphism in the angiotensin-converting-enzyme gene and
      blood pressure during ergometry in normal males.
AB  - A sample of 66 healthy, unrelated males with normal blood pressure were studied
      for a possible association between an insertion/deletion polymorphism in the gene
      coding for the angiotensin converting enzyme and blood pressure response to
      physical exercise. No association was found between the polymorphism and systolic
      blood pressure at rest and during stress. Statistically significant associations
      between the polymorphism and diastolic blood pressure were observed during
      exercise and post-stress. At maximal workload, among homozygotes for the
      deletion, the mean diastolic blood pressure was 93 (+/- 10) mmHg, among
      homozygotes for the insertion it was 82 (+/- 8) mmHg, among heterozygotes it was
      85 (+/- 10) mmHg. The difference was still statistically significant 3 minutes
      post-stress. The angiotensin converting enzyme polymorphism may be a marker for
      genetically determined differences in the response of the cardiovascular system
      to physical stress.

PMID- 9147896
TI  - Size of 22q deletions in four previously reported patients with conotruncal
      anomaly face syndrome.
AB  - Conotruncal anomaly face syndrome (CTAFS) was distinguished from velo-cardio
      facial syndrome (VCFS) in a bind study, yet shared the finding of 22q11.2
      deletions. This work has been extended to show that the 22q11.2 deletions in
      CTAFS greatly overlap those found in VCFS and many DiGeorge patients. The reason
      for dissimilar phenotypes with apparently similar 22q11.2 deletions is not yet
      known.

PMID- 9147897
TI  - Increased paternal age in CHARGE association.
AB  - The acronym CHARGE refers to a non-random clustering of congenital malformations
      whose cause remains unknown. Here, we report on a series of 41 patients and find
      a significant increase in mean paternal age of birth of CHARGE patients (33.7 +/-
      8 years) compared with the control population (30.8 +/- 5 years). In contrast,
      maternal age was not statistically different in patients and controls. These data
      suggest the possible role of a dominant mutation or, less likely, a subtle
      chromosomal abnormality in CHARGE association.

PMID- 9147898
TI  - Lack of association of angiotensin I-converting enzyme gene polymorphism and
      premature myocardial infarction in Mauritian Indians.
AB  - Eighty-five young Mauritian Indians, male survivors of premature myocardial
      infarction (MI) and thus belonging to a high risk group, were compared with 108
      stringently selected controls for a possible association between premature MI and
      an insertion/deletion (I/D) polymorphism in the gene encoding angiotensin I
      converting enzyme (ACE). The frequency of the D allele was 0.42 in the MI group
      and 0.43 in the control group, and thus no association between I/D polymorphism
      of ACE with susceptibility to early-onset MI was found in this population group.
      Other gene components of the renin-angiotensin system and lipid metabolism need
      to be explored to understand the genetic factors involved in causing MI at an
      early age.

PMID- 9147899
TI  - Population variation at the polymorphic ApaLI restriction enzyme site in intron 5
      of the WT1 gene.
AB  - We examined 63 unrelated individuals from the United States for the Apa-LI
      polymorphism in intron 5 of the WT1 gene. Allele frequencies of 0.13 and 0.87 for
      the A and B alleles, respectively, and a heterozygosity index of 24% contrast
      sharply with previous data obtained in the Japanese population where allele
      frequencies of 0.55 and 0.45 for the A and B alleles and a heterozygosity index
      of 59% were reported. These data suggest genetic heterogeneity at the WT1 locus,
      which may contribute to the differences in the incidence of Wilms tumor between
      the two population groups.

PMID- 9147900
TI  - CFC syndrome: report of familial cases.

PMID- 9147901
TI  - III European Conference on Systemic Lupus Erythematosus. Pisa, Italy, 12-14
      September 1996. Proceedings and abstracts.

PMID- 9147902
TI  - USAN council. List No.392. New names. Amlintide.

PMID- 9147903
TI  - USAN Council. List No.392. New names. Pramlintide.

PMID- 9147904
TI  - Vertebral osteomyelitis presenting with bilateral pleural effusions in a leprous
      patient.
AB  - We present a highly rare case of vertebral osteomyelitis due to Salmonella
      newport that was associated with pleural effusion in a leprous woman. The
      salmonella infection was considered to be precipitated by her hemolytic anemia
      resulting from dapsone. The direct spread of infection from the vertebrae led to
      the pleurisy.

PMID- 9147905
TI  - Atypical Streptococcus pyogenes from an ear discharge.
AB  - An atypical variant of Streptococcus pyogenes was isolated from a discharge from
      a child's ear. Although this variant streptococcus grew aerobically on chocolate
      agar, the isolate would not grow on blood agar, the medium used to screen for S.
      pyogenes, unless it was incubated anaerobically or incubated in air with
      cocarboxylase.

PMID- 9147906
TI  - Vitek GPS card susceptibility testing accuracy using direct inoculation from
      BACTEC 9240 blood culture bottles.
AB  - The emergent need for antimicrobial susceptibility testing (AST) data for the
      therapy of bacteremic patients has led to the development of rapid methods and
      local procedure modification of some commercial AST products such as the direct
      inoculation from blood culture systems. We compared the Vitek GPS card results
      using direct and standardized inoculation with a reference broth microdilution
      method for 112 consecutive staphylococcal bloodstream infections (seven drugs).
      Among the 28 Staphylococcus aureus strains, 0%-3.6% total error/drug was observed
      with both Vitek inoculation procedures. However, the only oxacillin-resistant
      strain was not detected (100% true very-major error). For 84 coagulase-negative
      staphylococci (CNS), the direct inoculation procedure had an 11.9% very-major
      error rate for oxacillin, ampicillin-sulbactam, and cephalothin, plus 4.8% very
      major error rate for ciprofloxacin and trimethoprim-sulfamethoxazole (total error
      rate 4.8%-16.7% for five of seven drugs compared). The Vitek direct inoculation
      procedure routinely missed 20.4% of oxacillin-resistant CNS strains. The use of
      Vitek direct inoculation procedures for staphylococcal bloodstream infection
      isolates (from BACTEC 9240 cultures) produced serious false-susceptible results;
      this procedure should be avoided in favor of routine package insert-recommended
      Vitek procedures or other reference-quality overnight incubation susceptibility
      tests.

PMID- 9147907
TI  - Antimicrobial activity and spectrum of sparfloxacin tested against erythromycin
      resistant Streptococcus pneumoniae isolates.
AB  - Recognition of a worldwide increase of penicillin-resistant Streptococcus
      pneumoniae and cross-resistance to other classes of antimicrobials have placed a
      great urgency on the need for new antimicrobial agents. Sparfloxacin, a novel
      pyridone carboxylic acid fluoroquinolone derivative was evaluated and compared to
      six other compounds for antimicrobial activity against erythromycin-resistant
      pneumococci (50 strains). The Etest susceptibility testing method was used to
      inoculate Mueller-Hinton agar supplemented with 5% sheep blood. There was
      extensive cross-resistance between erythromycin, clarithromycin (94%), and
      azithromycin (100%), but no cross-resistance was detected between
      macrolides/azalides and sparfloxacin (all strains susceptible at < or = 1.0 mu
      g/ml). Sparfloxacin (MIC90, 1 mu g/ml) was four-fold more active than
      ciprofloxacin and ofloxacin (MIC90, 4 mu g/ml). Sparfloxacin appears to possess
      excellent in vitro activity against erythromycin-resistant S. pneumoniae that
      were often highly resistant to beta-lactams, and further studies are recommended
      to investigate its in vivo efficacy against these multi-resistant organisms.

PMID- 9147908
TI  - False resistance to metronidazole by E-test among anaerobic bacteria
      investigations of contributing test conditions and medium quality.

PMID- 9147909
TI  - A new urea broth-based test to detect Helicobacter pylori presence in upper
      gastrointestinal biopsies.
AB  - The aim of this study was to evaluate the performance of a simple and inexpensive
      homemade urea test (U-test) to detect Helicobacter pylori in upper digestive
      tract biopsies. We tested and compared the U-test with three other diagnostic
      methods: the Clo-test, and culture and pathology in 110 patients randomly chosen
      at the endoscopy clinic. When using culture and/or pathology as the "gold
      standard," H. pylori was found to exist in 54 patients. Pathology was positive in
      50 cases (92.5%), culture in 49 (90.7%), the U-test in 45 (83.3%), and the Clo
      test in 43 (79.6%). With regard to culture pathology, the sensitivities of the U
      test and the Clo-test were 83.3% and 79.5%, respectively. Specificity was 100%
      for both methods. The kappa coefficient calculation between the U-test and the
      Clo-test was 0.98. The results show that the U-test is a reliable, fast, and
      inexpensive method for detecting H. pylori in upper gastrointestinal biopsies.

PMID- 9147910
TI  - Rapid antigen testing for group A Streptococcus by DNA probe.
AB  - The Gen-probe group A Streptococcus direct test (GASD), a nucleic acid probe
      assay for detecting GAS from throat swabs, has recently been developed. The test
      uses an acridium ester-labeled DNA probe which is complementary to the rRNA of
      Streptococcus pyogenes. In this study, 318 single culturette throat swabs were
      tested by this method using culture as a "gold standard." After plating onto
      trypticase soy agar plates with 5% sheep blood, swabs were stored at 4 degrees C
      for no more than 72 h before the probe assay was performed. Our patient
      population consisted of symptomatic outpatients seen in the Memorial Hospital
      Emergency Department and in the Family Care Center. After discrepancy testing,
      sensitivity, specificity, and positive and negative predictive values were 91.4%,
      97%, 91.4%, and 97%. The GASD is a rapid, easy-to-perform method for batch
      screening for streptococcal pharyngitis.

PMID- 9147911
TI  - Analytic performance and contamination control methods of a ligase chain reaction
      DNA amplification assay for detection of Chlamydia trachomatis in urogenital
      specimens.
AB  - A ligase chain reaction (LCR) DNA amplification assay that targeted the cryptic
      plasmid of Chlamydia trachomatis was developed to detect C. trachomatis
      urogenital tract infection. The objectives of this study were to determine the
      cutoff and analytic performance of the LCR assay and to characterize the
      effectiveness of its postdetection contamination control method. The assay's
      cutoff was determined after receiver-operator characteristic (ROC) analysis of
      4660 clinical data points. The assay detected one infectious unit per reaction of
      each of the 15 C. trachomatis serovars and did not cross-react with 13 Chlamydia
      pneumoniae strains, 13 Chlamydia psittaci strains, and 87 other bacteria, fungi,
      parasites, or viruses. In addition, the assay did not detect 77 processed urine
      specimens collected from patients with urinary tract infections caused by yeast
      or bacteria other than C. trachomatis. The assay was sufficiently precise to
      detect consistently two infectious units of C. trachomatis per reaction. False
      positive assay results attributable to contamination with amplified product were
      minimized by the use of standard procedures as well as by a postdetection
      chemical inactivation method that could reduce the amount of amplified LCR
      product by a factor of > or = 10(7).

PMID- 9147912
TI  - Dapsone penetrates cerebrospinal fluid during Pneumocystis carinii pneumonia
      prophylaxis.
AB  - Dapsone has been proposed as a prophylactic agent for both Pneumocystis carinii
      pneumonia (PCP) and reactivation cerebral toxoplasmosis. To determine whether
      dapsone penetrates the central nervous system, cerebrospinal fluid (CSF) and
      serum samples were drawn from patients taking dapsone for PCP prophylaxis. These
      samples were quantitatively assayed using high-performance liquid chromatography.
      Five AIDS patients and one cardiac transplant patient had CSF assayed for
      dapsone. Only one had evidence of CSF inflammation, resulting from a paraspinal
      abscess. Doses ranged from 50 mg 3 days/week to 100 mg/day, and levels were 0.30
      1.61 mu g/ml, which are in the range of inhibition of Toxoplasma gondii
      tachyzoites. This is the first report to demonstrate that dapsone enters the CSF,
      and supports preliminary clinical evidence that dapsone may have protective
      activity against cerebral toxoplasmosis when used for PCP prophylaxis.

PMID- 9147913
TI  - Antimicrobial susceptibility of clinical isolates of Acinetobacter baumannii.
AB  - The in-vitro activity of 18 antimicrobial agents alone or in combination against
      248 clinical isolates of Acinetobacter baumannii from Taiwan were tested by agar
      dilution. The MIC90S of ampicillin, amoxicillin, piperacillin, cefuroxime,
      cefotaxime, ceftriaxone, gentamicin, and amikacin were at least 128 mu g/ml.
      Ceftazidime, cefepime, sulbactam, clavulanic acid, and tazobactam presented
      moderate activity with MIC90S of 32, 16, 16, 32, and 32 mu g/ml, respectively.
      The increased activity of ampicillin/sulbactam, amoxicillin/clavulanic acid, and
      piperacillin/tazobactam was due to the intrinsic effect of sulbactam, clavulanic
      acid, and tazobactam, respectively. Imipenem, meropenem, and ciprofloxacin were
      the most active antimicrobial agents with MIC90S of 1, 1, and 0.5 mu g/ml,
      respectively. Nineteen isolates (7.7%) were resistant to all aminoglycosides and
      beta-lactam antibiotics, except carbapenems and ciprofloxacin. We are concerned
      about the multidrug resistance of A. baumannii in this study.

PMID- 9147915
TI  - Detection of oxacillin-resistance in Staphylococcus aureus by MicroScan MIC
      panels in comparison to four other methods.
AB  - Two hundred fifty-two isolates of Staphylococcus aureus were tested for oxacillin
      susceptibility by MicroScan Gram positive overnight and rapid MIC panels. Results
      were compared with nonautomated methods including disk diffusion, MRSA Crystal
      ID, and Etests using MRSA Screen Agar as reference. One hundred sixty-nine
      isolates (67.1%) were oxacillin-susceptible and 83 (32.9%) were resistant. All
      methods agreed for 234 (92.9%) isolates. Very major error rates were 1.2% for
      disk diffusion, 3.6% for Etest, and 0 for all other methods. Major error rates
      were 5.3% for MicroScan overnight panels, 3% for rapid panels, 2.4% for disk
      diffusion, 1.2% for Etest, and 0.6% for MRSA Crystal ID. Nine oxacillin
      susceptible isolates with borderline MICs and discrepant results for 1 or more
      methods were tested for the mec A gene and all were negative. Each was
      susceptible to beta lactam/beta lactamase inhibitor combinations, suggesting that
      false resistance may have been due to excessive beta lactamase production.
      Oxacillin-resistant S. aureus with borderline MICs determined by MicroScan should
      be confirmed by an alternate method. The most practical and cost-effective means
      among those we tested is the MRSA Screen Agar.

PMID- 9147914
TI  - Quality control guidelines for amoxicillin, amoxicillin-clavulanate,
      azithromycin, piperacillin-tazobactam, roxithromycin, ticarcillin, ticarcillin
      clavulanate, trovafloxacin (CP 99,219), U-100592, and U-100766 for various
      National Committee for Clinical Laboratory Standards susceptibility testing
      methods. Results from multicenter trials.
AB  - Quality control guidelines for standardized antimicrobial susceptibility test
      methods are critical to the continuing accuracy of the tests. In this report,
      quality control limits were proposed for 22 organism-antimicrobial combinations
      with minimum inhibitory concentration (MIC) ranges of three or four log2 dilution
      steps. Disk diffusion zone diameter ranges were proposed for azithromycin
      compared with Neisseria gonorrhoeae ATCC 49226 and ticarcillin with and without
      clavulanic acid tested against Staphylococcus aureus ATCC 25923. The data from
      five or six participating laboratories produced > or = 94.7% of results within
      proposed MIC limits, and 94.3%-99.0% of zones were found within suggested zone
      guidelines. These proposed quality control ranges should be validated by in-use
      results from clinical laboratories.

PMID- 9147916
TI  - [How many bodies are there in the body? Some remarks on neurophysiology during
      the Enlightenment].

PMID- 9147917
TI  - [Five hundred years of facts, theories and hypotheses on cerebral integration:
      some examples].

PMID- 9147918
TI  - [Birth and evolution of the biological concept of bisexuality].

PMID- 9147919
TI  - [The controversy between Gley and Moussu over the specificity of thyroid and
      parathyroid functions].

PMID- 9147920
TI  - [The chemical-physiological transformation of hygiene at the end of the 18th
      century].

PMID- 9147921
TI  - Proceedings of a network symposium of the European Association for the History of
      Medicine and Health. Strasbourg, France, March 26-27, 1993.

PMID- 9147922
TI  - Proceedings of the 5th International Conference on the Chemistry and Biology of
      Mineralized Tissues. Kohler, Wisconsin, USA, October 22-27, 1995. Session I.

PMID- 9147923
TI  - Proceedings of the 5th International Conference on the Chemistry and Biology of
      Mineralized Tissues. Kohler, Wisconsin, USA, October 22-27, 1995. Sessions II
      VIII.

PMID- 9147924
TI  - Removal of heterotopic ossifications followed by cobalt therapy after hip
      arthroplasty.
AB  - The authors report 7 cases in which removal of high grade ossification which
      developed after hip arthroplasty was performed: all of the patients were treated
      postoperatively by radiation therapy with the purpose of preventing recurrence of
      ossification. After surgery ossification was present, but to a moderate degree,
      in 6 out of 7 cases examined; movement had clearly improved. The results obtained
      show that removal surgery is justified if movement of the hip is considerably
      impaired (ankylosis) and that prevention plays an essential role and must be
      carried out every time that the patient risks the development of ossification.

PMID- 9147925
TI  - Pulmonary embolism associated with use of bone cement during hip arthroplasty.
AB  - Main circulatory (heart frequency, HF, intra-artery pressure, AP ECG) and
      respiratory (arterial oxyhemoglobin saturation SaO2, end-tidal CO2) arterial gas
      analysis (HGA) parameters were recorded continually during cemented hip
      arthroplasty in 70 consecutive non-selected patients. The use of cement did not
      cause any change in the parameters obtained in 21 of the cases, reduction in
      arterial oxygen pressure (PaO2) ranging from 11% to 38% was observed in 44 cases,
      associated with simultaneous reduction in ETCO2 in 11 cases. The reduction in
      ETCO2 was an isolated finding in 5 of the patients. AP decreased by more than 10%
      in only 2 cases and there was arrhythmia in another 2 cases. These findings are
      strongly suggestive of pulmonary embolism encouraging the hypothesis of gas
      embolism previously suggested by other authors. In patients with little coronary
      or pulmonary reserve use of cement means an increased risk of severe hemodynamic
      complications.

PMID- 9147926
TI  - Hydroxyapatite as metallic prosthesis coating: preliminary clinical experience.
AB  - The authors report the radiographic results of 65 An. C.A. prosthetic stems
      coated with hydroxyapatite and followed-up at least 24 months after implantation.
      A comparison with a homogeneous group of aluminum-coated An.C.A. stems showed
      that hydroxyapatite-coated stems are characterized by better osteointegration,
      with a clearly inferior incidence of radiolucent lines at the bone/prosthesis
      interface. Macroscopic observation and histologic examination carried out on two
      stems removed because of persistent pain to the thigh revealed partial resorption
      and fragmentation of the coating. The authors believe that this phenomenon, the
      object of other observations reported in the literature, may indicate the reduced
      stability of the coating in the long run, and as such further in-depth study is
      required.

PMID- 9147927
TI  - Traumatic lesions of the acetabular triradiate cartilage (presentation of four
      cases and considerations on treatment).
AB  - Four cases of fracture of the triradiate cartilage (TC) are reported, all of
      which may be classified as epiphyseal detachments. Two of the patients were
      submitted to osteosynthesis of the posterior column: results were very
      satisfactory in one of the cases for which long-term follow-up was obtained. The
      other two cases, treated non-surgically, developed meta-traumatic actabular
      dysplasia probably due to association with crushing phenomena (Salter-Harris V)
      in the germinative area of TC. Despite the favorable results obtained in the case
      that was submitted to surgery, the authors believe that conservative treatment is
      best in this type of lesion, and that surgical reduction should be performed only
      in cases of instability and severe displacement, once surgical reduction has
      failed.

PMID- 9147928
TI  - The effect of intra-arterial versus intravenous cisplatinum in the neoadjuvant
      treatment of osteosarcoma of the limbs: the experience at the Rizzoli Institute.
AB  - The effect of intra-arterial versus intravenous infusion of cisplatinum on the
      histological response of osteosarcoma of the limbs was evaluated based on the
      results of three studies in which CDP was preoperatively associated with MTX and
      ADM (1st study), and with MTX, ADM, and IFO (2nd and 3rd studies). In the
      chemotherapeutic protocol that involved 3 drugs the percentage of "good
      histological responses to chemotherapy" (defined as tumor necrosis > 90%) was
      significantly higher in the 40 patients who were administered CDP by intra
      arterial infusion as compared to that observed in the 39 patients treated with
      CDP by intravenous route (78% versus 46%: P .004). In the two sequential studies
      where 4 drugs were used, the percentage of good histological responses was
      essentially the same for patients treated with CDP administered intravenously,
      and for those treated with CDP administered intra-arterially (78% versus 84%).
      Regardless of the route of infusion used to administer cisplatinum the percentage
      of "good" histological responses was significantly higher in the 109 patients
      treated with the 4-drug protocol as compared to the 79 patients treated with the
      3-drug protocol (82% vs 62%; P .04). This difference may essentially be
      attributed to the higher percentage of good responses observed in the 4-drug
      protocol in patients treated with CDP administered intravenously (78% vs 46% for
      patients treated i.v. with the 3-drug protocol; P .006). For the patients instead
      treated with CDP administered intra-arterially the percentage of good responses
      was essentially the same with the 4-drug protocol and with the 3-drug protocol
      (84% vs 78%; P ns). These data lead us to conclude that in the neoadjuvant
      treatment of osteosarcoma of the limbs a preoperative 4-drug protocol (MTX, CDP,
      ADM, IFO) is more effective than a 3-drug protocol (MTX, CDP, ADM), and that in a
      4-drug preoperative chemotherapy protocol intra-arterial infusion of CDP does not
      offer particular advantages as compared to intravenous infusion.

PMID- 9147929
TI  - Ultrasound in the evaluation of bone fragility caused by osteoporosis: a
      comparison between different sites of measurement.
AB  - The authors compare two different measurement sites of ultrasound transmission
      velocity (UTV) in discriminating between subjects with or without vertebral
      fracture caused by osteoporosis. To this purpose a total of 150 women in
      menopause, of which 50 with vertebral fracture documented radiologically, for
      whom UTV was measured in the distal radius and in the patella, were examined. In
      both sites measurement of UTV in fractured women (1531.9 m/sec in the distal
      radius, and 1825.1 m/sec in the patella) was significantly less than for healthy
      women (1557.4 m/sec in the distal radius and 1874.5 m/sec in the patella) and
      there was a significant inverse linear correlation with age. The logistic
      regression shows that in both sites ultrasound examination is capable of
      significantly discriminating between osteoporotic women with fracture and those
      without fracture (odds ratio of the distal radius = 38.857, odds ratio of the
      patella = 7.822). A comparison of the discriminating capacity of the two
      measurement sites shows that the ORC curves for the distal radius (area = 0.773)
      is significantly greater than that of the patella (area = 0.684). Our study
      confirms that UTV can discriminate healthy subjects from osteoporotic ones, and
      it shows that the method in question has greater diagnostic sensitivity in the
      distal radius than in the patella.

PMID- 9147930
TI  - Paralyzing disc herniation: a contribution.
AB  - The authors report a case of paralyzing disc herniation that caused atrophy of
      the sura muscles to the right, many years after the occurrence of two episodes of
      acute lumbar sciatic pain that was successfully treated conservatively. Diagnosis
      was formulated based exclusively on muscular insufficiency in the region affected
      and remote pathologic history.

PMID- 9147931
TI  - The effects of cigarette smoke on the progression of septic pseudarthrosis of the
      tibia treated by Ilizarov external fixator.
AB  - The authors conducted a study to evaluate the effects of cigarette smoke on the
      healing of septic pseudarthrosis of the tibia treated by ilizarov external
      fixator. A total of 31 patients of both sexes were chosen, and the healing time
      in relation to the habit of smoking was examined. The results have shown that the
      healing time in non-smokers as compared to smokers was shorter by 33%. The
      difference is highly significant. This shows that abstention from smoking during
      treatment should be given maximum importance in prevention.

PMID- 9147932
TI  - Meyer's dysplasia epiphysealis.
AB  - Meyer's femoral cephalic dysplasia (FCD) is a rare affection that is often
      confused with Perthes' disease from which it differs in terms of both treatment
      and prognosis. A constant feature is the absence of the nucleus of ossification
      that does not occur until 15-18 months of age; at times there are multiple nuclei
      of ossification, so that the epiphysis has a "morulated" aspect. Fusion of the
      various centers of ossification occurs at about 5 years of age. The epiphysis
      does not collapse and it preserves its density and its structure. Differential
      diagnosis involves Perthes' disease and other pathologies such as multiple
      dysplasia epiphysealis, hypothyroidism, dyschondroplasia.

PMID- 9147933
TI  - Two cases of hyperparathyroidism initially diagnosed as aneurysmal cyst.
AB  - The authors present two cases of primary hyper-parathyroidism initially diagnosed
      as aneurysmal cyst. The aspects of differential diagnosis are discussed, and the
      importance of evaluating all of the diagnostic elements in order to formulate a
      correct diagnosis is emphasized.

PMID- 9147934
TI  - Late recurrence and endocranial metastasis caused by giant cell tumor.
AB  - A case of giant cell tumor localized in the proximal end of the right tibia,
      initially treated by simple curettage is described. After 11 years there was
      local recurrence, confirmed anatomopathologically, observed during wide resection
      and reconstruction by arthroplasty plus homoplastic grafting. After a few months
      there were metastatic lesions in the left parietooccipital and right
      retroorbitary area. Biopsy of the parietooccipital lesion showed giant cells in a
      sarcomatous stroma. The patient died after several attempts at chemotherapy. Even
      if only sporadic cases have been described of late recurrences and of
      extrapulmonary metastases for giant cell tumors, the case presented here is
      exceptionally rare. The factors that influence recurrence of these tumors and
      their ability to metastasize is discussed.

PMID- 9147935
TI  - Baker's pseudocyst in the prosthetic knee affected with aggressive granulomatosis
      caused by polyethylene wear.
AB  - It is our belief that this is the first histologically documented case of
      popliteal cyst secondary to early failure of a cementless knee prosthesis, that
      occurred after 4 years. The walls of the cyst presented with granulomatous
      reaction to polyethylene particles. In prosthetic reimplantation successive to
      excision of the cyst we observed a recurrence of cysts and osteointegration of
      the prosthetic components, that made reimplantation difficult. Histological
      assessment of the synovial tissue, periprosthetic tissue and underlying bone
      showed granulomatous reaction to polyethylene debris. A "tumor" in a patient that
      has a knee prosthesis can be caused by implant failure. In cases of early failure
      wear forms large particles and their migration at the bone-prosthesis interface
      may be obstructed and thus cause a different biological response. If
      reimplantation is necessary osteointegration of the implants may make surgery
      difficult.

PMID- 9147936
TI  - [Therapy of HIV infection: combination drug therapy effective, immunotherapy
      still experimental].

PMID- 9147937
TI  - [Clinical relevance of immunoscintigraphy with 99mTc-labelled anti-CEA antigen
      binding fragments in the follow-up of patients with colorectal carcinoma.
      Assessment of surgical resectability with a combination of conventional imaging
      methods].
AB  - BACKGROUND AND OBJECTIVE: Conventional imaging modalities (e.g. ultrasound,
      computed tomography [CT] and magnetic resonance [MRI]) are used in the routine
      follow-up of patients with colorectal carcinoma. But they have only limited
      diagnostic reliability. This study was undertaken to evaluate immunoscintigraphy
      (IS) with 99mTc-labelled anti-CEA antigen-binding fragments (CEA-Scan) alone or
      combined with conventional imaging methods. PATIENTS AND METHODS: 22 patients,
      operated on for colorectal carcinoma and suspected of having a recurrence,
      underwent scintigraphy with CEA-scan and whole-body single-photon emission
      computed tomography (SPECT). All results were compared with those by computed
      tomography (CT) and, in 19 of the patients, with histological findings (surgical
      specimen or biopsy). The potential influence of the scintigraphic results on
      surgical management was analysed retrospectively with respect to the preoperative
      estimate of tumour resectability. RESULTS: Lesion-based sensitivity of IS was
      94%, diagnostic accuracy 92%, both being unrelated to the CEA-serum level. When
      CT and IS were concordant regarding resectability, this estimate was correct in
      all instances. But in case of discordance the results of IS were verified
      operatively in 88% of cases. In no patient was there measurable immune reaction
      with formation of human-mouse-antibodies (HAMA). CONCLUSIONS: These results
      indicate that IS together with SPECT can achieve reliable and sensitive
      localisation of tumour lesions. CEA-Scan does not, contrary to other murine
      antibodies, cause the formation of HAMA. The combination of IS with conventional
      imaging techniques can improve noninvasively the estimate of surgical
      resectability.

PMID- 9147938
TI  - [Spontaneous retroperitoneal hematoma in adrenal metastasis].
AB  - HISTORY AND CLINICAL FINDINGS: A 58-year-old man was hospitalized because of
      acute dull upper abdominal pain, radiating into the right flank and lower
      abdomen. The past history was unremarkable expect for thyroidectomy, performed 30
      years previously for thyroid carcinoma. There was painful resistance on palpation
      of the right upper abdomen. The patient had not recently sustained any trauma.
      BIOCHEMICAL AND IMAGING INVESTIGATIONS: Erythrocyte sedimentation rate was
      increased to 38 mm/h, haemoglobin concentration was 11.7 g/dl but fell to 9.9
      g/dl within the first 24 hours. Ultrasound and computed tomography (CT) revealed
      a large retroperitoneal mass (5 x 6.5 x 15 cm), its density of 64 Hounsfield
      units most strongly suggesting an haematoma. CT also showed enlargement of the
      right adrenal. Chest radiography demonstrated a space-occupying lesion in the
      right upper lobe. DIAGNOSIS, TREATMENT AND COURSE: As a retroperitoneal haematoma
      of uncertain aetiology was suspected, a laparotomy was performed. The haematoma
      was evacuated and the adrenal, showing tumours changes, was excised.
      Histologically it was a mucocellular metastasis. The chest radiograph suggested
      carcinoma of the lung as the primary. The illness took a rapidly fatal course.
      Autopsy confirmed a poorly differentiated adenocarcinoma of the lung. CONCLUSION:
      Trauma or anticoagulation should be considered first in the differential
      diagnosis of retroperitoneal haematoma of uncertain aetiology. However, adrenal
      metastasis should be thought of as a rare possibility.

PMID- 9147939
TI  - [Rational diagnosis of vaginal discharge].

PMID- 9147940
TI  - [Fluoxetine].

PMID- 9147941
TI  - [Myoarthropathies of the chewing system--more than a problem of dental medicine].

PMID- 9147942
TI  - [From "Becquerel-rays" to radioactivity. 100 anniversary of the discovery of
      natural radioactivity by Henri Becquerel (1896)].

PMID- 9147943
TI  - [Risk of thrombosis with increased anticardiolipin antibodies].

PMID- 9147944
TI  - [Therapy in hypertrophic obstructive cardiomyopathy].

PMID- 9147945
TI  - Abstracts of papers presented at the Neonatal Society Meeting. June 1996.

PMID- 9147946
TI  - Microbial lipases: structures, function and industrial applications.

PMID- 9147947
TI  - Evidence that the active site in type II dehydroquinase from Streptomyces
      coelicolor is near the single tryptophan.

PMID- 9147948
TI  - Exploring qualitative research in general practice. Proceedings of a conference.
      Durham, United Kingdom, 19 March 1996.

PMID- 9147949
TI  - Tolerance of human fetal retinal pigment epithelium xenografts in monkey retina.
AB  - BACKGROUND: RPE transplantation offers the possibility of treating certain forms
      of retinal degeneration. Understanding how to optimize the surgical technique for
      performing RPE transplantation, especially in primates, is therefore of
      considerable interest. METHODS: Fifteen patch RPE transplants were performed in
      six monkeys. The transplant sites were examined at follow-up by ophthalmoscopy,
      biomicroscopy, fluorescein angiography and histology. Foveal and peripheral
      retinal transplants were compared. RESULTS: Human fetal RPE xenografts can
      survive without rejection for at least 6 months after transplantation in monkey
      retina. Such grafts form a basal lamina and make intimate contacts with the outer
      segments of the host. Both rods and cones retain a normal appearance when in
      contact with unrejected transplants. Rejection occurred in only 30% (3/10) of the
      peripheral but in 60% (3/5) of the foveal transplants. CONCLUSIONS: Cultured
      human fetal RPE patch transplants can survive and maintain local photoreceptor
      integrity for relatively long periods of time in monkey subretinal space without
      immunosuppression. Rejection, when it occurs, is more frequent near the fovea.

PMID- 9147950
TI  - A model for light toxicity of cultured human retinal pigment epithelium.
AB  - BACKGROUND: The effect of visible light on human retinal pigment epithelial
      (HRPE) cells has not been characterized under conditions that provide strict
      thermal control. METHODS: HRPE cells were isolated and grown to confluence. Cells
      were exposed to light in an incubator in which the cell temperature was
      controlled in response to a temperature sensor maintained in the tissue culture
      medium. Cells were exposed: (A) for 24, 36, and 48 h; and using a 24-h exposure
      followed by 24 h darkness; (B) at varying intensities of light using neutral
      density filters; (C) under a yellow filter; and (D) with a 12-h on-off cyclic
      light. RESULTS: (A) Light exposure of 36 and 48 h resulted in significant
      cytotoxicity, while the initial 24-h exposure did not induce subsequent
      cytotoxicity. (B) Light irradiance levels from 43 to 54 mW/cm2 were required to
      demonstrate cytotoxicity. (C) Use of a yellow filter did not eliminate the
      observed cytotoxicity. (D) Cyclic exposure did not result in significant
      cytotoxicity. CONCLUSION: This study establishes a model and basic parameters of
      light toxicity to HRPE cells in vitro using strict temperature control that may
      be used to evaluate photochemical injury to HRPE cells.

PMID- 9147951
TI  - Immunomodulating activity of allopurinol in experimental lens-induced uveitis.
AB  - PURPOSE: The aim of this study was to evaluate the immunomodulating activity of
      allopurinol using a model of lens-induced uveitis (LIU) and to compare these
      effects to those of steroids. METHODS: We tested the sera of both LIU and control
      rats against western blots (WB) of SDS-PAGE separations of protein fractions from
      normal and LIU rat lenses. These blots were scanned using digital image analysis.
      A newly developed technique was used to compare the complex autoantibody (AAB)
      repertoires. Five groups of LIU rats were investigated: no treatment; single
      doses of methylprednisolone (MPR; 7.5 mg/kg body wt.i.v.); allopurinol (AL; 50
      mg/kg body wt. i.v.); a combination of both drugs (AL and MPR); repeated
      application of AL (ALFR; 50 mg/kg body wt.i.v. every 2 weeks during the
      immunization period and a daily dose of approx. 25 mg/kg body wt. orally).
      RESULTS: Immunization induced complex antibody repertoires against lens proteins.
      Antibody repertoires of LIU rats were identical, regardless of whether the
      proteins were obtained from control, uveitis eyes, or corresponding healthy eyes
      of the same individual. AL showed a dose-dependent immunological effect in LIU
      treatment. Given as a single dose, AL revealed no significant change in the AAB
      repertoire; however, ALFR showed very clear modification of the AAB repertoires
      compared to both controls and rats receiving steroids. CONCLUSIONS: These results
      suggest dose-dependent effects of allopurinol in LIU treatment. Repeated
      application during the immunization period induced a strong immunomodulating
      effect of AL that was not observed after single doses.

PMID- 9147952
TI  - Effects of eye muscle proprioceptive activation on eye position in normal and
      exotropic subjects.
AB  - BACKGROUND: Activation of muscle spindles by vibration of eye muscles is known to
      induce illusory movements of fixated targets, but the effects on eye position
      have not been studied, either in normal subjects or in patients with exotropia.
      METHODS: Eye position was recorded from the covered, non-dominant eye with an
      infrared system in 11 subjects with normal eyes and binocular vision and in 10
      patients with exotropia and abnormal binocular function. Activation of eye muscle
      spindles was done by vibration at 70 Hz of the inferior and lateral rectus
      muscles of the dominant eye, fixating a light-emitting diode in subdued light.
      RESULTS: Vibratory activation of proprioceptors in the inferior rectus muscle
      induced an eye movement mainly directed upward in both normal and exotropic
      subjects. The magnitude of the movement was on average 2.7 deg in normals and 2.4
      deg in exotropes. Lateral rectus vibration induced a movement that was mainly
      temporally directed (abduction) of an average 2.1 deg in normal subjects, but a
      nasally directed (adduction) movement of 4.2 deg in exotropic subjects. In normal
      subjects the eye movement is of the same direction as the earlier reported visual
      illusory movements induced by the same type of proprioceptive activation, but in
      exotropic subjects the movements is in the opposite direction. CONCLUSIONS:
      Proprioceptive activation of eye muscles affects eye position, and the results
      also indicate that signals from eye muscles are processed differently in normals
      and strabismics, probably depending on the level of binocular function.

PMID- 9147954
TI  - Adaptation to monocular torsion after macular translocation.
AB  - PURPOSE: To document the functional outcome of two patients following successful
      macular translocation for the treatment of severe subretinal hemorrhage in age
      related maculopathy. METHODS: The retina was surgically rotated around the optic
      nerve with translocation of the fovea either upward or downward to an area of
      healthy retinal pigment epithelium. In the postoperative period, visual function
      was carefully studied with emphasis on adaptation to torsion. RESULTS: Visual
      acuity in one patient improved from 20/200 to 20/80 and the other patient
      remained at 20/200. Both patients developed horizontal and vertical strabismus
      with torsion of up to 55 degrees. After a prolonged period of occlusion of the
      unoperated eye, both patients were subjectively able to adapt to monocular
      torsion. However, adaptation under binocular conditions did not occur.
      CONCLUSION: Macular translocation was successful in improving visual acuity in
      one patient, with no improvement in the second. Both patients had significant
      ocular torsion and strabismus, but under monocular conditions they were
      successful in perceptually adapting to the change in the visual environment. Fear
      of cyclotorsion should not be a deterrent to considering macular translocation as
      a possible treatment option for severe subretinal macular hemorrhage if the
      patient is willing to accept monocular vision.

PMID- 9147953
TI  - Contrast sensitivity in diabetic pregnancy.
AB  - PURPOSE: To evaluate the correlation between the changes in contrast sensitivity
      and retinopathy throughout pregnancy in diabetic women with mild background
      diabetic retinopathy. METHODS: Contrast sensitivity (Vistech 6500 Contrast Test
      System) was measured in 22 type I diabetic women with mild background retinopathy
      [0-16 microaneurysms (MAs)/eye and occasional small intraretinal hemorrhages] and
      10 healthy pregnant women at the 12th and 32nd weeks of pregnancy and 3 months
      after delivery. Red-free fundus photography was also performed at all visits.
      RESULTS: Throughout pregnancy contrast sensitivity was lower in the diabetics
      than in the controls at 1.5, 3.0, and 6.0 cycles per degree (cpd). During the
      course of pregnancy, contrast sensitivity decreased at 1.5 and 6.0 cpd in
      patients with more than five new MAs compared to those with fewer than five new
      MAs during pregnancy. Likewise, contrast sensitivity decreased at 6 cpd in
      patients with an increase in MA count during pregnancy and at 6 and 12 cpd in
      patients with a baseline MA count of two or more MAs. CONCLUSIONS: Contrast
      sensitivity, especially at low to mid-range spatial frequencies, is decreased in
      diabetic women with mild retinopathy. Even small changes in retinopathy are
      reflected in a decrease in contrast sensitivity during and after pregnancy. Thus,
      contrast sensitivity seems to be a sensitive indicator of changes in minimal
      background retinopathy.

PMID- 9147955
TI  - Variability of contour line alignment on sequential images with the Heidelberg
      Retina Tomograph.
AB  - BACKGROUND: The influence of the contour line alignment software algorithm on the
      variability of the Heidelberg Retina Tomograph (HRT) parameters remains unclear.
      METHODS: Nine discrete topographic images were acquired with the HRT from the
      right eye in six healthy, emmetropic subjects. The variability of topometric data
      obtained from the same topographic image, analyzed within different samples of
      images, was evaluated. A total of four mean topographic images was computed for
      each subject from: all nine discrete images (A), the first six of those images
      (B), the last six of those nine images (C), and the first three combined with the
      last three images (D). A contour line was computed on the mean topographic image
      generated from the nine discrete topographic images (A). This contour line was
      then applied to the three other mean topographic images (B, C, and D), using the
      contour line alignment in the HRT software. Subsequently, the contour line on the
      mean topographic images was applied to each of the discrete members of the
      particular images subsets used to compute the mean topographic image, and the
      topometric data for these discrete topographic images was computed successively
      for each subset. Prior to processing each subset, the contour line on the
      discrete topographic images was deleted. This strategy provided a total of three
      analyses on each discrete topographic image: as a member of the nine images (mean
      topographic image A), and as a member of two subsets of images (mean topographic
      image B, C, and/or D). The coefficient of variation (100 x SD/mean) of the
      topographic parameters within those three analyses was calculated for each
      discrete topographic image in each subject ("intraimage" coefficient of
      variation). In addition, a coefficient of variation between the nine discrete
      topographic images ("interimage" coefficient of variation) was calculated.
      RESULTS: The "intraimage" and "interimage" variability for the various
      topographic parameters ranged between 0.03% and 3.10% and between 0.03% and
      24.07% respectively. The "intraimage" coefficients of variation and "interimage"
      coefficients of variation correlated significant (r2 = 0.77; P < 0.0001).
      CONCLUSION: A high "intraimage" variability, i.e. a high variability in contour
      line alignment between sequential images, might be an important source of test re
      test variability between sequential images.

PMID- 9147956
TI  - Management of fibrous histiocytoma of the corneoscleral limbus: report of a case
      and review of the literature.
AB  - BACKGROUND: Fibrous histiocytomas of the corneoscleral limbus are rare tumors. We
      present an additional case and review the treatment approaches in the literature.
      So far, only light and electron microscopic studies have been performed. We used
      immunohistochemical stains to further characterize the cellular composition.
      METHODS: The excised lesion was routinely fixed and processed for light
      microscopy and immunohistochemical studies. For comparison, three dermal fibrous
      histiocytomas were also examined and processed similarly. RESULTS: The
      corneolimbal tumor was mainly composed of fibroblasts and histiocytes with a
      large amount of interstitial collagen, arranged in a storiform pattern.
      Immunohistochemical stains were positive for histiocytes, fibroblasts, and a
      marker for mesenchymal cells. The staining pattern of the dermal lesions was
      similar. CONCLUSION: Fibrous histiocytomas of the corneolimbal region are
      morphologically benign, slowly growing and infiltrative tumors. Complete
      resection, especially of the deep margin, is suggested. The immunohistochemical
      staining pattern is similar to that of dermal fibrous histiocytomas, which behave
      in a benign manner.

PMID- 9147957
TI  - CD44 expression in the developing human retina.
AB  - BACKGROUND: CD44, the transmembrane adhesion molecule, is expressed in the fetal
      brain and supposed to mediate neuroglial, interactions. We evaluated the
      expression and distribution of CD44 in the developing human retina. METHODS: Four
      developing human eyes were evaluated at 6, 10, 16, and 21 weeks of gestation, as
      well as the eyes of one infant and four adults. Frozen sections were
      immunohistochemically stained with monoclonal antibodies to three human CD44
      clones (BU52, F10-44-2, and DF1485) and to vimentin, and antiserum to glial
      fibrillary acidic protein (GFAP). Specimens were evaluated by light and electron
      microscopy. RESULTS: Positive immunostaining for CD44 was first detected at 21
      weeks of gestation in the longitudinal fibers that extended from the inner to the
      outer limiting membrane and around capillary vessels with the simultaneous
      expression of vimentin and GFAP. Immunoelectron microscopy demonstrated the
      presence of CD44 on the surface of Muller cells and astrocytes. CD44 was faintly
      seen in the Muller cells in the periphery and definitely present in the
      astrocytes in the infant and adult retinas. CONCLUSION: CD44 was expressed in
      Muller cells at a late stage of fetal development and in the fetal, infant, and
      adult astrocytes, which suggests that it is important in the morphogenesis and
      homeostasis of the neural retina.

PMID- 9147959
TI  - Helicobacter pylori: need for guidance.

PMID- 9147958
TI  - Suppression of actively induced experimental autoimmune uveoretinitis by CD4+ T
      cells.
AB  - BACKGROUND: Helper/inducer T cells that exert an inhibitory effect on disease
      induction have been recently found in many experimental models. In order to
      clarify the mechanisms of spontaneous remission of experimental autoimmune
      uveoretinitis (EAU), we investigated the inhibitory effect and the phenotype of
      the post-recovery suppressor cells. METHODS: In a series of experiments, we
      separated spleen cells of rats that had recovered from EAU. Three groups of
      spleen cells, CD4+ T, CD8+ T and B cells, were each adoptively transferred into
      naive syngeneic rats before active immunization with retinal soluble antigen (S
      Ag) and Freund's complete adjuvant or passive immunization with uveitogenic T
      cells from donor rats. Inflammation was examined clinically and histologically.
      RESULTS: The development of EAU could be significantly prevented by adoptive
      transfer of CD4+ T cells, whereas CD8+ T cells could not suppress the onset.
      However, post-recovery CD4+ T cells failed to inhibit EAU induced by passive
      immunization with uveitogenic T cells. CONCLUSION: These findings indicate that
      CD4+ post-recovery (suppressor) T cells may play an important role in the
      remission of EAU.

PMID- 9147960
TI  - Pancreatic tuberculosis.

PMID- 9147961
TI  - A computer program for calculation of sample size.
AB  - Sample size must be determined while planning a study to ensure that valid
      conclusions can be drawn when the study is over. different formulae for
      calculating the required size of the sample are used for different study designs
      and situations. A computer program is described here to ease the complexity of
      calculation of sample size for studies designed to use students 't' test.

PMID- 9147962
TI  - Temperature measurement in febrile intensive care patients: which method?

PMID- 9147963
TI  - Normal saline instillation before suctioning: helpful or harmful?

PMID- 9147964
TI  - PCR for Mycobacterium tuberculosis.

PMID- 9147965
TI  - Genetic determination of the meso-diaminopimelate biosynthetic pathway of
      mycobacteria.

PMID- 9147966
TI  - The Impact of Anxiety on the Health Care System. Proceedings of a symposium.
      Stowe, Vermont, March 15-16, 1996.

PMID- 9147967
TI  - Biomechanical studies of the remodeling of knee joint tendons and ligaments.
AB  - Living tissues and organs are dynamic and change their mechanical properties and
      structure in response to stress alteration as a phenomenon of functional
      adaptation and optimal operation. This phenomenon is called 'Tissue Remodeling',
      and Wolff's law on bone remodeling is widely known. Several recent studies have
      shown that fibrous connective tissues such as tendons and ligaments also have the
      ability of remodeling. However, relatively little is known about the stress and
      motion effects on tissue homeostasis in biological soft tissues. This article
      primarily deals with changes of the biomechanical properties of knee joint
      tendons and ligaments through a wide variety of treatment modalities, including
      stress deprivation, recovery after stress deprivation, and stress enhancement.
      The experimental results indicate that tendons and ligaments have an ability to
      adapt in response to the change of stress if the extent of stress alteration is
      within allowable ranges.

PMID- 9147968
TI  - Energy transfer mechanisms as a compensatory strategy in below knee amputee
      runners.
AB  - Below knee amputee runners exhibit abnormalities in the mechanical work
      characteristics of the lower extremity musculature during stance phase. The most
      significant abnormality is a marked reduction in the mechanical work done in the
      stance phase prosthetic limb. Energy transfer across the hip joint to the trunk
      during deceleration of the swing phase leg may be an important energy
      distribution mechanism to compensate for the reduced work done during prosthetic
      stance phase. Five unilateral below knee amputee runners wearing the SACH
      prosthetic foot and 5 normal subjects were studied. All subjects ran at a
      controlled velocity of 2.8 ms(-1) while kinematic and ground reaction force data
      were collected. Using a four segment linked segment model and an inverse dynamics
      approach joint moments, muscle power outputs, mechanical work values and energy
      transfers across the hip were calculated. The total amount of energy transferred
      during swing phase and the energy transferred out of the swing phase leg into the
      trunk were both significantly greater than normal. Energy transfer mechanisms are
      important in influencing the lower extremity energetics during swing phase. In
      addition, the 74 percent increase in energy transfer out of the intact swing
      phase limb combined with the temporal characteristics of this energy flow
      suggests that energy transfer may be an adaptive mechanism that allows energy
      redistribution to the trunk which may partially compensate for the reduced power
      output of the stance phase prosthetic limb.

PMID- 9147969
TI  - The influence of muscles on knee flexion during the swing phase of gait.
AB  - Although the movement of the leg during swing phase is often compared to the
      unforced motion of a compound pendulum, the muscles of the leg are active during
      swing and presumably influence its motion. To examine the roles of muscles in
      determining swing phase knee flexion, we developed a muscle-actuated forward
      dynamic simulation of the swing phase of normal gait. Joint angles and angular
      velocities at toe-off were derived from experimental measurements, as were pelvis
      motions and muscle excitations. Joint angles and joint moments resulting from the
      simulation corresponded to experimental measurements made during normal gait.
      Muscular joint moments and initial joint angular velocities were altered to
      determine the effects of each upon peak knee flexion in swing phase. As expected,
      the simulation demonstrated that either increasing knee extension moment or
      decreasing toe-off knee flexion velocity decreased peak knee flexion. Decreasing
      hip flexion moment or increasing toe-off hip flexion velocity also caused
      substantial decreases in peak knee flexion. The rectus femoris muscle played an
      important role in regulating knee flexion; removal of the rectus femoris actuator
      from the model resulted in hyperflexion of the knee, whereas an increase in the
      excitation input to the rectus femoris actuator reduced knee flexion. These
      findings confirm that reduced knee flexion during the swing phase (stiff-knee
      gait) may be caused by overactivity of the rectus femoris. The simulations also
      suggest that weakened hip flexors and stance phase factors that determine the
      angular velocities of the knee and hip at toe-off may be responsible for
      decreased knee flexion during swing phase.

PMID- 9147970
TI  - Measures of paraspinal muscle performance do not predict initial trunk kinematics
      after tripping.
AB  - The ability to limit the trunk flexion associated with an anteriorly directed
      trip is a determinant of successful recovery of recovering postural stability and
      is subservient to rapidly detecting and correcting the imposed trunk flexion in
      the available time. This experiment tested the hypothesis that subjects
      demonstrating greater eccentric trunk/hip extension strength, faster voluntary
      reaction times, shorter automatic response latencies, and larger automatic
      activation amplitudes of the paraspinal muscles, would demonstrate less trunk
      flexion following a trip. An isokinetic protocol was used to obtain measures of
      trunk extension strength, response latencies, and activation amplitudes. Motion
      analysis methods were used to quantify trunk kinematics during the positioning
      phase of recovery following an induced trip. Statistically significant and
      functionally meaningful relationships between eccentric strength of the trunk/hip
      extensors, voluntary-reaction time, automatic reaction time, activation
      amplitudes and trunk kinematics failed to emerge. Thus, although automatic and
      voluntary paraspinal muscle responses have the potential to limit trunk flexion
      during the positioning phase of recovery, the task may be achieved through
      intersegmental factors or other muscular sources such as the gluteus maximus and
      hamstrings.

PMID- 9147971
TI  - Mechanics of ventricular torsion.
AB  - Recent research suggests that left ventricular torsion is an important indicator
      of cardiac function. We used two theoretical models to study the mechanics of
      this phenomenon: a compressible cylinder and an incompressible ellipsoid of
      revolution. The analyses of both models account for large- strain passive and
      active material behavior, with a muscle fiber angle that varies linearly from
      endocardium to epicardium. Relative to the end- diastolic configuration, the
      predicted torsion exhibits several experimentally observed features, including a
      peak near end systole, rapid untwisting during isovolumic relaxation, and
      increased twist near the apex. The magnitude of the twist is sensitive to the
      fiber architecture, the ventricular geometry, and the compressibility and
      contractility of the myocardium. In particular, the model predicts that the
      systolic twist increases with increasing compressibility, contractility, and wall
      thickness, while it decreases with increasing cavity volume. The peak twist
      approximately doubles (from about 0.02 to 0.04 rad cm(-1)) with a doubling of
      myocardial compressibility or with a change in the endocardial/epicardial muscle
      fiber angles from 90/ -90 degrees to 60/ -60 degrees. The twist is less sensitive
      to changes in contractility and ventricular geometry. These findings provide a
      basis for interpreting measurements of ventricular torsion in the clinical
      setting.

PMID- 9147973
TI  - A model of the flexion-extension motion in the elbow joint some problems
      concerning muscle forces modelling and computation.
AB  - This paper represents an application of a general approach for modelling and
      mathematical investigation of the human upper limb considered in a previous paper
      (Raikova, 1992, J. Biomechanics 25, 857-867). Six ways of modelling the muscle
      force in a plane are suggested and compared to each other. A model of the flexion
      extension motion in the elbow joint is proposed, which includes two extensor
      muscles and three flexor muscles. An optimization task is formulated and solved
      analytically using the Lagrange multipliers method with an objective function
      dependent on the n-th power of the muscle forces moduli: sigma c(i)F(i)/(n) (n >
      1). The influence of a set of parameters (the power n in the objective function,
      the weight coefficients c i, the lever arms of the modelled muscle forces, an
      external force applied to the forearm) on the predicted muscle forces and on the
      joint reaction is investigated. The results demonstrate that strictly positive
      and continuous solutions for all muscle forces (for synergistic muscles, also for
      the antagonistic ones) may be simultaneously predicted if the coefficients C(i)
      are properly chosen.

PMID- 9147972
TI  - Predictive value of proximal femoral bone densitometry in determining local
      orthogonal material properties.
AB  - Models which are based on non-invasive bone measurements may in the future be
      able to successfully identify individual subjects at an increased risk for hip
      fracture; thus, we designed a study to determine the usefulness of dual-energy X
      ray absorptiometry (DXA) and quantitative computed tomography (QCT) in predicting
      the local material properties of human proximal femoral cancellous bone. There
      has been some disagreement in the scientific literature regarding appropriate
      predictive models for local material properties of cancellous bone. We sought to
      confirm that density-mechanical property relationships were consistent from
      subject to subject, and that three-dimensional QCT measurements were stronger
      predictors of mechanical properties than two-dimensional DXA results. Linear and
      power fit relationships between these densitometric measures and material
      properties were also examined to determine which were more appropriate. Bone
      cubes from specific regions of highly oriented trabeculae were analyzed
      separately to determine if cube orientation had an effect on mechanical
      properties independent of bone density. Ten pairs of ex vivo femurs (five male,
      five female; age 30-93, mean age 62) were prepared such that specific anatomic
      planes were visible radiographically. Both QCT and DXA measurements were made on
      all 20 femurs. Cancellous bone cubes were obtained proceeding along two distinct
      directions from the proximal end of each femur pair. Unexpectedly, the density
      modulus relationships among these ten donors were found to be significantly
      different at p <0.01 (83 percent of the tests were different at p <0.0001).
      Density-strength regressions were also significantly different at p <0.01, but
      this effect was not as consistent nor as statistically significant. In general,
      the QCT method did not produce predictions of local cancellous bone material
      properties superior to the DXA method. The linear and power fit models appeared
      to produce consistent results, with neither being obviously more advantageous.
      These density measurements explained at best 30-40 percent of the variance in
      modulus and 50-60 percent of the variance in ultimate stress. The orientation of
      cancellous cubes in the principal compressive trabeculae region was a significant
      contributor to mechanical properties (p= 0.0001) independent of bone density.
      This finding was not as dramatic in the femoral neck cancellous bone region.

PMID- 9147974
TI  - Determination of collagen-proteoglycan interactions in vitro.
AB  - The objective of this study was to characterize the physical interactions of the
      molecular networks formed by mixtures of collagen and proteoglycan in vitro. Pure
      proteoglycan aggrecan solutions, collagen (type II) suspensions and mixtures of
      these molecules in varying proportions and concentrations were subjected to
      viscometric flow measurements using a cone-on-plate viscometer. Linear
      viscoelastic and non-Newtonian flow properties of these solutions and suspensions
      were described using a second-order statistical network theory for polymeric
      fluids (Zhu et al., 1991, J. Biomechanics 24, 1007-1018). This theory provides a
      set of material coefficients which relate the macroscopic flow behavior of the
      fluid to an idealized molecular network structure. The results indicated distinct
      differences between the flow properties of pure collagen suspensions and those of
      pure proteoglycan solutions. The collagen network showed much greater shear
      stiffness and more effective energy storage capability than the proteoglycan
      network. The relative proportion of collagen to proteoglycan is the dominant
      factor in determining the flow behavior of the mixtures. Analysis of the
      statistical network theory indicated that the collagen in a collagen-proteoglycan
      mixture enhances molecular interactions by increasing the amount of entanglement
      interactions and/or the strength of interaction, while aggrecan acts to reduce
      the number and/or strength of molecular interactions. These results characterize
      the physical interactions between type II collagen and aggrecan and provide some
      insight into their potential roles in giving articular cartilage its mechanical
      behavior.

PMID- 9147975
TI  - Determination of spinal facet joint loads from extra articular strains--a
      theoretical validation.
AB  - Loads on the facet joints of the lumbar spine may play a role in low back pain.
      Abnormal loading of the facets, either primarily or as a consequence of disc
      degeneration, may accelerate their degeneration. Study of these phenomena is
      difficult, since here are few methods for a direct measure of facet forces
      occurring in vivo. The authors developed a method for the direct measure of facet
      forces in a canine animal model of spine disease using strain gages. The method
      used empirical calibration of the strain gages, which was used to reduce
      experimental strain output to facet force during function. In this Technical
      Note, a theoretical model is formulated, solved and validated which gives a
      theoretical basis for the data reduction method. The facet is modeled as a
      cantilevered plate and deformations, as function of applied normal load, solved
      for using a finite difference method. The model is validated by comparison with
      two experiments with strain-gaged facets. Results from the model show that a
      minimum of three strain gages is required to determine uniquely the location and
      magnitude of an applied load to the facet, and that at least two gages should be
      placed in the region where the cranial articular process joins the pedicle with
      the gage axis parallel to that of the process. Plate surface strains were found
      to be insensitive to changes in the area of the applied loads, for a given
      resultant force magnitude. The method may be useful in other applications in
      which resultant force magnitude and location need to be measured on plate-like
      structures.

PMID- 9147976
TI  - Accuracy of an electromagnetic tracking device: a study of the optimal range and
      metal interference.
AB  - The positional and rotational accuracy of a direct-current magnetic tracking
      device commonly used in biomechanical investigations was evaluated. The effect of
      different metals was also studied to determine the possibility of interference
      induced by experimental test fixtures or orthopaedic implants within the working
      field. Positional and rotational data were evaluated for accuracy and resolution
      by comparing the device output to known motions as derived from a calibrated grid
      board or materials testing machine. The effect of different metals was evaluated
      by placing cylindrical metal samples at set locations throughout the working
      field and comparing the device readings before and after introducing each metal
      sample. Positional testing revealed an optimal operational range with the
      transmitter and receiver separation between 22.5 and 64.0 cm. Within this range
      the mean positional error was found to be 1.8 percent of the step size, and
      resolution was determined to be 0.25 mm. The mean rotational error over a 1-20
      degree range was found to be 1.6% of the rotational increment with a rotational
      resolution of 0.1 degrees. Of the metal alloys tested only mild steel produced
      significant interference, which was maximum when the sample was placed adjacent
      to the receiver. At this location the mild steel induced a positional difference
      of 5.26 cm and an angular difference of 9.75 degrees. The device was found to be
      insensitive to commonly used orthopaedic alloys. In this study, the
      electromagnetic tracking device was found to have positional and rotational
      errors of less than 2 percent, when utilized within its optimal operating range.
      This accuracy combined with its insensitivity to orthopaedic alloys should make
      it suitable for a variety of musculoskeletal research investigations.

PMID- 9147977
TI  - A two-part, viscoelastic foot model for use in gait simulations.
AB  - A three-dimensional, two-part model of the foot, for use in a simulation of human
      gait, is presented. Previous simulations of gait have not included the foot
      segment (e.g. Siegler et al., 1982, J. Biomechanics 15, 415-425) or have fastened
      it to the ground (e.g. Onyshko and Winter, 1980, J. Biomechanics 13, 361-368). A
      foot model based on viscoelastic elements (e.g. Meglan, 1991, Ph.D. thesis, Ohio
      State Univ.), allows more freedom of movement and thus models the physical system
      more closely. The current model was developed by running simulations of the foot
      in isolation from just before heel contact to just after toe-off. The driving
      inputs to the simulation were the resultant ankle joint forces and moments taken
      from a gait analysis. Nine linear, vertically oriented spring/damper systems,
      positioned along the midline of the foot were used to model the combined
      viscoelastic behaviour of the foot, shoe and floor. Associated with each vertical
      spring/damper system were two orthogonally placed, linear, horizontal dampers
      used to provide the shear components of the ground reaction force. Torques at the
      metatarsal-phalangeal joint were supplied by a linear, torsional spring and
      damper. Control about the vertical axis and the long axis of the foot was
      achieved by the use of linear, torsional dampers. The predicted kinetic and
      kinematic values are very similar to those taken from the gait analysis. The
      model represents an improvement over previous work because the transition from
      swing to stance was smooth and continuous without the foot being constrained to
      any specific trajectory.

PMID- 9147978
TI  - In vitro laxity-testers for knee joints of mice.
AB  - The knee joints of mice can be used as a model for studying the effects of
      interventions on knee laxity. The goal of this study was to quantify knee joint
      laxity in vitro. Three devices were developed: a positioning- and cementing
      device, an anterior-posterior (AP) laxity tester and a varus-valgus (VV) laxity
      tester. The positioning and cementing device was used to position the joint in a
      reproducible way and to attach clamping pins to the proximal femur and distal
      tibia using PM MA. The clamping pins were used to fix the joint to the AP- and VV
      testers. In both testers the load was applied by means of a spindle-actuated
      spring while load and displacements were measured simultaneously. The load-
      displacement data were used to calculate displacement and compliance parameters.
      The performance of the testers was evaluated by testing 5 normal knee joints of 5
      mice. Total AP-translation at + or - 0.8 N was 0.43 (+ or - 0.16 S.D.) mm with
      compliances of 0.14 (+ or - 0.05 S.D.) mm N(1) and 0.12 ( + or - 10.05 S.D.) mm
      N(-1) at 0.8 N posterior and anterior force, respectively. Total VV-rotation at +
      or - 4 Nmm was 17.2 (+ or - 2.6 S.D.) degrees with compliances of 0.9 degrees
      Nmm(-1) (+ or - 0.2 degrees Nmm(-1) S.D.) and 1.0 Nmm(-1) (+ or - 0.4 degrees
      Nmm(-1) S.D.) at 4 Nmm valgus and varus moment, respectively. The contributions
      of the deformations of the bones and the fixtures to the rotations were
      negligible in the VV-test. In the AP-test they account for approximately 0.07 ( +
      or - 0.03 S.D.)mm of the total AP-translation. This will not affect the
      utilization of the device for comparative analysis. It is concluded that in in
      vitro evaluation of AP- and VV-laxity in knees of mice is feasible with
      sufficient accuracy for evaluation of changes after ligament damage.

PMID- 9147979
TI  - Hip impact velocities and body configurations for voluntary falls from standing
      height.
AB  - Fall dynamics have largely been ignored in the study of hip fracture etiology and
      in the development of hip fracture prevention strategies. In this study, we asked
      the following questions: (1) What are the ranges of hip impact velocities
      associated with a sideways fall from standing height? (2) What are the ranges of
      body configurations at impact? and (3) How do protective reflexes such as muscle
      activation or using an outstretched hand influence fall kinematics? To answer
      these questions, we recruited six young healthy athletes who performed voluntary
      sideways falls on a thick foam mattress. Several categories of falls were
      investigated: (a) muscle-active vs muscle-relaxed falls; (b) falls from a
      standing position or from walking; and (c) falls in which an outstretched arm was
      used to break the fall. Each fall was videotaped at 60 frames s(-1). Fall
      kinematics parameters were obtained by digitizing markers placed on anatomical
      points of interest. The mean value for vertical hip impact velocity was 2.75 ms(
      1) (+ or - 0.42 ms(-1) [S.D.]). The mean value for trunk angle (the angle between
      the trunk and the vertical) was 17.3 degrees (+ or - 11.5 degrees [S.D.]). We
      found a 38 percent reduction in the trunk angle at impact, and a 7 percent
      reduction in hip impact velocity for relaxed vs muscle-active falls. Finally,
      regarding the. falls in which an outstretched arm was used, only two out of the
      six subjects were able to break the fall with their arm or hand. For the
      remaining subjects hip impact occurred first, followed by contact of the arm or
      hand.

PMID- 9147981
TI  - Change in trabecular architecture as measured by fractal dimension.
AB  - The objective of this work was to expose dried trabecular bone material to a
      decalcifying environment and to quantify the change in the spatial distribution
      of the bone with a fractal measure. Digitized radiographic images were produced
      from four separate slices of human vertebral bone as they dissolved within a
      solution of nitric acid. Pixel data from a region of interest (ROI) within the
      trabecular bone were used to estimate the time-dependent change in fractal
      dimension of the ROI as the bone dissolved. Results demonstrated that a change in
      the spatial distribution of trabecular material may be expressed in terms of a
      concurrently changing estimate of the fractal dimension.

PMID- 9147980
TI  - Accuracy of a video strain measurement system.
AB  - The purpose of this study was to determine the accuracy of a video system which
      our laboratory has been using to measure soft tissue strain. Both static and
      dynamic error analyses were performed to assess the accuracy of our video system.
      Static error was defined as the amount of movement reported by the video system
      for markers that were stationary. Dynamic error was defined as the difference
      between the motion of the markers as reported by the video system and their
      actual motion. Two sets of fluorescent markers were attached to a servo-hydraulic
      materials test machine. One marker set was attached to the hydraulic actuator
      (moving markers) and the other set was attached to the base of the machine
      (stationary markers). Five different marker sizes, five camera distances, and
      seven different loading rates were studied. Results indicated that the static
      error was independent of marker size, and that the dynamic error was independent
      of the loading rate and marker size for loading rates of 50% of the camera field
      of view (CFV) per second or slower. For loading rates greater than 50 percent of
      CFV per second, the marker size did have an affect on the dynamic error. The mean
      static error was found to be 0.026 percent of CFV and the mean dynamic error was
      found to be 0.062 percent of CFV.

PMID- 9147982
TI  - Improved agreement of foot segmental power and rate of energy change during gait:
      inclusion of distal power terms and use of three-dimensional models.
AB  - Traditional models used to calculate foot segmental power have yielded poor
      agreement between foot power and the rate of energy change during the stance
      phase of gait and limited the applicability of foot segmental power analyses to
      swing phase only. The purpose of this study was to improve the agreement of foot
      segmental power and rate of energy change by using more inclusive models to
      calculate foot segmental power and energy. The gait of 15 adult subjects was
      studied and models were used to calculate foot segmental power that included
      either the proximal terms only (Model P, the most common method in the
      literature) or both proximal and distal terms (Model PD, a mathematically
      complete model). Power and energy terms were computed in two ways, from sagittal
      plane vector components only (two-dimensional condition) and from complete three
      dimensional components (three-dimensional condition). Results revealed that the
      more inclusive the model, the higher the agreement of foot power and rate of
      energy change. During stance phase, Model P produced poor agreement (r(c) =
      0.108) for both two-dimensional and three-dimensional conditions, Model PD-2D
      yielded higher agreement (r(c) = 0.645), and Model PD-3D exhibited nearly perfect
      agreement (r(c) = 0.956). The advantages of a segmental power analysis include
      the ability to identify the mechanisms of energy transfer into and out of the
      foot during movement. The results of this study suggest that foot power analyses
      are valid when using Model PD-3D to describe foot function during locomotion.

PMID- 9147983
TI  - Thickness measurement of soft tissue biomaterials: a comparison of five methods.
AB  - Thickness measurement in soft connective tissues is a continuing problem due to
      the apparent compression of the tissue by micrometer-type gauges. We have
      compared five methods for the measurement of thickness: (1) a Mitutoyo non
      rotating thickness gauge; (2) a custom-built, instrumented thickness gauge which
      was strain-gauged to measure contact force; (3) a commercial Hall effect probe
      (Panametrics Magna-Mike); (4) a custom-built electrical resistance probe; and (5)
      measurement of fresh frozen histological sections under polarized light. Using
      bovine pericardium as a test material, all the methods examined were adequate to
      assess sample-to-sample and location-to-location differences in thickness. The
      resistance gauge gave significantly greater thicknesses than did the other
      methods, with little or no compression; indeed, extrapolation to zero load of
      thickness readings from the instrumented gauge yielded identical thickness.
      Thicknesses measured by frozen sections were indistinguishable from those
      measured with the non-rotating gauge, the instrumented gauge under 0.5-1.2 g
      compressive load, or the Hall effect probe. With the correct technique, the
      simple and inexpensive non-rotating gauge remains a pragmatic choice for
      thickness measurement in planar soft tissue.

PMID- 9147984
TI  - Visual guidance to forceplates does not influence ground reaction force
      variability.

PMID- 9147986
TI  - An insert in the motor domain determines the functional properties of expressed
      smooth muscle myosin isoforms.
AB  - Smooth muscle myosin isoforms of the heavy chain and the essential light chain
      have been hypothesized to contribute to the different shortening velocities of
      phasic and tonic smooth muscles, and to their different affinities for MgADP. We
      used the baculovirus/insect cell system to express homogeneous heavy meromyosin
      molecules differing only in seven amino acid insert (QGPSFSY) in the motor domain
      near the active site, or in the type of essential light chain isoform. Myosin
      from tonic rabbit uterine smooth muscle lacks the heavy chain insert, while
      myosin from phasic chicken gizzard contains it. The properties of a mutant
      uterine heavy meromyosin with added insert, and a mutant gizzard heavy meromyosin
      with the insert deleted, were compared with their wild type progenitors.
      Phosphorylated heavy meromyosins with the insert have a twofold higher enzymatic
      activity and in vitro motility han heavy meromyosins without the insert. These
      functional properties were not altered by the essential light chain isoforms. The
      altered motility caused by the insert implies that it modulates the rate of ADP
      release, the molecular step believed to limit shortening velocity. The insert may
      thus account in part for both the lower sensitivity to MgADP and the higher
      shortening velocity of phasic compared to tonic smooth muscles.

PMID- 9147987
TI  - Rapid regeneration of power stroke in contracting muscle by attachment of second
      myosin head.
AB  - When Lombardi and colleagues reported the phenomenon of rapid regeneration of the
      power stroke after a quick release of muscle fibre during a tetanus, they gave an
      explanation in terms of detachment of cross-bridges and re-attachment further
      along the thin filament. We show here that the phenomenon can also be explained
      on assumptions that lead to a majority of myosin molecules being attached by only
      one head during steady isometric contraction; the other head may then become
      attached after a quick release and can add its contribution to the early tension
      recovery after a second release.

PMID- 9147988
TI  - Towards the understanding of muscle contraction and its regulation. A symposium
      in honor of John Gergely, MD, PhD.

PMID- 9147989
TI  - The XXV European Muscle Congress: La Grand-Motte, Montpellier, France 14-17
      September 1996.

PMID- 9147985
TI  - Myosin light chain kinases.

PMID- 9147990
TI  - Actin filament mechanics in the laser trap.
AB  - Numerous biological processes, including muscular contraction, depend upon the
      mechanical properties of actin filaments. One such property is resistance to
      bending (flexural rigidity, EI). To estimate EI, we attached the ends of
      fluorescently labelled actin filaments to two microsphere 'handles' captured in
      independent laser traps. The positions of the traps were manipulated to apply a
      range of tensions (0-8 pN) to the filaments via the microsphere handles. With
      increasing filament tension, the displacement of the microspheres was
      inconsistent with a microsphere-filament system that is rigid. We maintain that
      this inconsistency is due to the microspheres rotating in the trap and the
      filaments bending near either attachments to accommodate this rotation. Fitting
      the experimental data to a simple model of this phenomena, we estimate actin's EI
      to be approximately 15 x 10(3) pNnm2, a value within the range of previously
      reported results, albeit using a novel method. These results both: support the
      idea that actin filaments are more compliant than historically assumed; and,
      indicate that without appropriately pretensioning the actin filament in similar
      laser traps, measurements of unitary molecular events (e.g. myosin displacement)
      may be significantly underestimated.

PMID- 9147991
TI  - The complex-type oligosaccharide binding lectin Datura stramonium agglutinin
      detects type II A muscle fibres in the branchial biceps from man and cat.
AB  - Complex-type oligosaccharides were detected in the sarcoplasm of muscle fibres
      from cat and human biceps using lectins and anticarbohydrate antibodies. The
      lectin Datura stramonium agglutinin strongly stained type II A fibres as
      identified by myosin ATPase activity after alkaline and acid preincubation. In
      contrast, all muscle fibres showed a moderate coarse granular staining after
      incubation with Tetracarpidum conophorum agglutinin and Telfairia occidentalis
      agglutinin which recognize tri-antennary complex glycans poorly bound by D.
      stramonium agglutinin. Strong sarcoplasmic staining in all muscle fibres was
      obtained after incubation with an antibody against branched N-acetyllactosamine
      structure while an antibody against binary 2 --> 3 sialyllactosamine glycans
      failed to detect the muscle fibres. Treatment of the muscle sections with
      sialidase prior to incubation with D. stramonium agglutinin did not influence the
      lectin staining pattern. Staining of blots from electrophoretically separated
      muscle proteins obtained by homogenization, solubilization and centrifugation of
      small muscle pieces showed D. stramonium agglutinin binding to a number of bands
      ranging from 200 kDa to 30 kDa. No D. stramonium agglutinin positive bands were
      observed in blots from separated mitochondrial proteins while blots from
      sarcoplasmic reticulum separated by electrophoresis stained many bands in the
      range from 200 kDa to 30 kDa. It may be concluded that all muscle fibres in human
      and cat biceps hold intracellular non-sialylated complex-type oligosaccharides
      and further, that a specific tri-antennary complex-type glycoform is strongly
      expressed in type II A fibres as recognized by D. stramonium agglutinin. These
      results indicate a different glycosylation of certain myofibrillar-associated
      proteins in muscle fibre types.

PMID- 9147993
TI  - Regional variations of muscle fibre characteristic in m. semitendinosus of
      growing cattle.
AB  - The objectives of the present study were to elaborate an intra-muscular profile
      of metabolic enzyme equipment, contractile and morphometric features along the
      longitudinal axis of m. semitendinosus at various ages throughout the growth
      phase. Thirty-seven male Montbeliard cattle, about half of them castrated, were
      representatively allocated to various slaughter dates, scheduled at 4, 8, 12 and
      16 months of age. Samples were collected from proximal, medial and distal
      locations of m. semitendinosus. Isocitrate dehydrogenase (aerobic metabolism) and
      lactate dehydrogenase (anaerobic metabolism) were measured
      spectrophotometrically. Contractile muscle type was classified by quantification
      of myosin heavy chain I isoform proportion using the sensitive enzyme-linked
      immunosorbent assay. Mean muscle fibre area was obtained on histologically
      stained cross-sections utilizing an image analysis system. Our results indicate
      the existence of a regular intra-muscular pattern of muscle fibre traits along
      the length of m. semitendinosus, with decreasing glycolytic activities and
      concomitantly an increase in oxidative capacity towards the distal extremity. The
      metabolic characteristics were in good agreement with decreasing cross-sectional
      muscle fibre areas and the slow myosin heavy chain I isoform proportion becoming
      gradually more abundant from proximal to distal regions of the muscle. Moreover,
      the observed gradient was found to be closely related to age and diminished with
      advanced physiological maturity. At the final slaughter age (16 months) no
      differences among the distinct portions were detected, m. semitendinosus was
      longitudinally homogeneous in all the characteristics studied.

PMID- 9147992
TI  - Analysis of cDNAs encoding Drosophila melanogaster myosin light chain kinase.
AB  - Myosin light chain kinase regulates the activity of myosin by phosphorylating the
      myosin regulatory light chain. Here we describe the cloning and characterization
      of cDNAs encoding Drosophila melanogaster myosin light chain kinase. We amplified
      a fragment of the Drosophila mlck gene using degenerate primers homologous to a
      highly conserved region in myosin light chain kinase proteins of vertebrate
      species. We used the gene fragment to isolate corresponding Drosophila mlck
      cDNAs. The deduced protein sequence of the cDNAs shows high homology to the
      catalytic and regulatory domains of vertebrate nonmuscle, smooth muscle and
      skeletal muscle myosin light chain kinase. Protein motifs I and II, which are
      present in vertebrate nonmuscle and smooth muscle myosin light chain kinase, but
      not in skeletal muscle myosin light chain kinase, are also present in Drosophila
      myosin light chain kinase. Transcript and cDNA analysis shows the gene encodes
      multiple messages and is expressed in nonmuscle and muscle cells, including the
      adult indirect flight muscle. Genomic Southern analysis and chromosome
      hybridization suggest mlck is a single copy gene which maps to chromosome band
      52D, and is not haplo-insufficient for flight.

PMID- 9147994
TI  - The survival of embryonic cardiomyocytes transplanted into damaged host rat
      myocardium.
AB  - In this study, attempts were made to replace damaged myocardium of adult rats
      with embryonic grafts. To this purpose pieces of embryonic ventricular myocardium
      were prelabelled with 4',6-diamidino-2-phenylindole and placed into a damaged
      area of the host myocardium. The hearts containing the grafts were then examined
      between 2 days and 5-7 months later. Initially the 4'-6-diamindino-2-phenylindole
      labelled cells were localized only at the site of grafting, but by 2-5 weeks they
      migrated along the ventricular surface of the heart. Nevertheless the greatest
      density of grafted cells was always found in the damaged area. At all time points
      studied, the myogenic phenotype of the 4'-6-diamindino-2-phenylindole-labelled
      cells was maintained, as the cells contained myosin heavy chains. In addition,
      immunolabelling with antibodies against cardiac gap junction proteins revealed
      that initially gap junctions were scattered within the transplanted tissue but
      with time they became more organised, firstly by alignment into rows along the
      developing myofibres and then into structures that resembled intercalated discs.
      Thus the grafted embryonic cardiac myocytes survived in an adult host myocardium
      and expressed characteristics typical of heart cells.

PMID- 9147995
TI  - Contractile properties and myosin heavy chain composition of newborn rat soleus
      muscles at different stages of postnatal development.
AB  - This study was undertaken to correlate some of the functional characteristics
      with the myofibrillar composition in myosin heavy chain isoforms on newborn and
      adult rat soleus muscles. The following postnatal ages were chosen in order to
      determine the role of innervation in the establishment of the mature muscle
      phenotype: before (postnatal day 6), when (postnatal day 12), and after (days 17
      and 23) the monosynaptic innervation appeared. The steady state of definitive
      innervation was controlled on adult muscles (i.e. approximately 13 weeks). Muscle
      maturation was followed by ATPase staining and fibre diversity was observed at
      postnatal day 12. The functional properties of skinned bundles isolated from
      newborn rats were determined by Calcium/Strontium activation characteristics
      (Tension/pCa and pSr relationships). From postnatal days 6 to 17, the Soleus
      bundles exhibited Calcium/Strontium activation characteristics intermediate
      between slow and fast fibre populations previously described in muscles. At day
      23, the Calcium/Strontium activation characteristics of the soleus were closer to
      those of a slow type. Moreover, we observed a decrease in Ca affinity concomitant
      with the installation of the monosynaptic innervation, and an increase of the
      slow type I during postnatal development. Finally, this work reported a greater
      correlation between the Calcium/Strontium activation parameters and the myosin
      heavy chain isoform composition at the postnatal days when the mature
      monosynaptic innervation pattern occurred.

PMID- 9147997
TI  - Cross-bridge kinetics studied with staircase shortening in single fibres from
      frog skeletal muscle.
AB  - The kinetics of actin-myosin interaction has been studied in single active muscle
      fibres by repetitively eliciting tension transients with staircase shortening,
      consisting in a sequence of step releases of identical size (1-5 nm per half
      sarcomere) imposed at regular time intervals (3-11 ms). Under sarcomere length
      clamp conditions, the quick phase of tension recovery following each step in the
      staircase is the manifestation of the working stroke by synchronized cross
      bridges. Different average shortening velocities are obtained by varying both the
      size of the step and the time interval between steps. Ti, the tension just before
      each step in the sequence, T2, the tension attained at the end of the quick phase
      of tension recovery, decrease with the number of steps, reaching a steady state
      value, which is lower the larger the shortening velocity. In agreement with
      previous results on tension response to steady shortening, the overall shortening
      necessary to approach the steady state values of Ti and T2 is about 15 nm. The
      normalized amplitude of quick tension recovery (T2r), which is measured by the
      ratio of the amount of tension recovered at the end of the quick phase (T2-T1)
      over the tension drop simultaneous with the step (Ti-T1), has been used to
      measure the extent of the working stroke elicited by each step in the staircase.
      The steady state value of T2r decreases progressively with the increase of
      shortening velocity. At velocities higher than 0.5 microns s-1 per half-sarcomere
      the steady state value of T2r is attained after a transitory depression, which
      reaches a maximum for an amount of overall shortening increasing from about 8 nm
      up to about 13 nm with increase in shortening velocity from 0.5 to 1.4 microns s
      1 per half-sarcomere. The velocity-dependent transitory depression of T2r can be
      explained with the mechanical-kinetic model described previously. In the model
      cross-bridges cycle through two pathway distinct for the kinetics of the
      detachment/reattachment process. Shortening promotes a redistribution of cross
      bridges interacting in the isometric conditions among the various states of the
      force-generating process. Shortening at high speed, preventing most of cross
      bridges from undergoing the relatively fast (100 s-1) detachment/reattachment
      process, uncovers a rate limiting step in the cycle at the end of the 12 nm
      working stroke. Under these conditions, the finding that the fraction of the
      working stroke elicited by each step is transitory depressed with respect to the
      steady state value reveals that in the original isometric state a large fraction
      of interacting cross-bridges was accumulated near the beginning of the working
      stroke.

PMID- 9147996
TI  - Induction of molecular and mechanical transformations in canine skeletal muscle
      by chronic neuromuscular stimulation.
AB  - The canine latissimus dorsi was stimulated at 1 Hz via the thoracodorsal nerve
      for 70 days. Seven days of muscle stimulation caused muscle mass, fibre cross
      sectional areas, and tetanic tensions to decrease. Fourteen days of stimulation
      produced marked decreases in Ca(2+)-uptake rates in a membrane fraction
      containing sarcoplasmic reticulum. At this time there was a decline in fusion
      frequency, but no statistically significant changes in time-to-peak tension,
      total contraction times, or half-relaxation times. With 42 days of stimulation a
      switch from the fast-twitch to the slow-twitch phenotype was indicated by
      elevations in the levels of expression of the slow-twitch isoforms of
      sarco(endo)plasmic reticulum Ca(2+)-ATPase and myosin heavy chain-I, and
      increases in half-relaxation times, total contraction times and time-to-peak
      tensions. Decreases in muscle shortening velocity correlated negatively with
      increases in myosin heavy chain-I levels. Up-regulation of the slow-twitch
      isoforms of sarco(endo)plasmic reticulum Ca(2+)-ATPase increases in half
      relaxation times. The changes in the slow-twitch isoform of sarco(endo)plasmic
      reticulum Ca(2+)-ATPase and myosin heavy chain-I levels indicated coordinate
      expression of these two proteins in chronically stimulated muscles.

PMID- 9147998
TI  - Stealing a nurse's human dignity.

PMID- 9147999
TI  - Human immunodeficiency virus infection modifies the natural history of chronic
      parenterally-acquired hepatitis C with an unusually rapid progression to
      cirrhosis.
AB  - BACKGROUND/AIMS: To investigate the possible role of HIV infection in the natural
      history of chronic parenterally-acquired hepatitis C. METHODS: A multicenter
      cross-sectional study was performed in 547 patients with chronic parenterally
      acquired hepatitis C with or without HIV infection (116 HIV-positive and 431 HIV
      negative). Approximate duration of HCV infection was estimated in all patients
      included, and histologic diagnoses made at different time intervals following HCV
      infection were analyzed in both groups. Factors related to serum HCV-RNA levels
      were also investigated. RESULTS: Histologic findings were similar in liver
      biopsies from both HIV-infected and noninfected patients. However, in the first
      10 years, 13 out of 87 (14.9%) HIV-positive subjects developed cirrhosis, in
      comparison with 7 out of 272 (2.6%) in the HIV-negative group (p < 0.01). Similar
      results were found in the first 5 and 15 years, respectively, and most of the HIV
      negative patients with cirrhosis (42 out of 56) developed cirrhosis in a time
      interval longer than 15 years. Consequently, mean interval from estimated time of
      HCV infection to cirrhosis was significantly longer in HIV-negative than HIV
      positive patients (23.2 vs. 6.9 years; p < 0.001). Chronic active hepatitis (with
      and without cirrhosis) and long duration of HCV infection were significantly
      associated with higher HCV load (p < 0.05). Finally, HIV-positive patients with
      CD4+ cell counts > 500 cells/ml showed a lower HCV load than those with < 500
      cells/ml (p < 0.05). CONCLUSIONS: HIV infection modifies the natural history of
      chronic parenterally-acquired hepatitis C with an unusually rapid progression to
      cirrhosis. HIV-related immunodeficiency may be a determinant of higher hepatitis
      C viremia levels and more severe liver damage.

PMID- 9148000
TI  - Reducing environment protects sinusoidal lymphocytes isolated from normal human
      liver from apoptosis.
AB  - BACKGROUND/AIMS: We previously reported that the populations of lymphocytes and
      the expression of activated antigens in human sinusoidal mononuclear cells were
      different from those in peripheral blood mononuclear cells. Attempts to culture
      these cells for further study failed because they died rapidly under standard
      culture conditions in vitro after isolation from the liver. In this study, we
      evaluated the characteristics of cell death and the effects of various culture
      conditions on the viability of these cells. METHODS: Sinusoidal mononuclear cells
      were isolated from University of Wisconsin solution that had been perfused
      through the portal veins of normal healthy human livers harvested for
      transplantation into living related recipients. RESULTS: 70% of sinusoidal
      mononuclear cells cultured in vitro were nonviable within 48 h after isolation,
      while only 10% of peripheral blood mononuclear cells died under the same
      conditions. Sinusoidal mononuclear cells showed DNA ladder formation of DNA on
      electrophoresis and characteristic morphological pattern on electron microscopic
      examination that suggested they had died in an apoptotic manner. The addition of
      human liver extracts or 2-mercaptoethanol and reduced glutathione to the cultures
      rescued the sinusoidal mononuclear cells from apoptosis. Furthermore, diamide, a
      sulfhydryl group specific oxidant, negated the effect of the liver extract.
      CONCLUSION: In comparison with peripheral blood mononuclear cells, human
      sinusoidal mononuclear cells were more subject to death by apoptosis ex vivo,
      which was reversed by exogenous agents producing reducing conditions. These
      results suggested that hepatic sinusoidal mononuclear cells might express a
      different sensitivity to redox environment than peripheral blood mononuclear
      cells.

PMID- 9148001
TI  - Hepatic vascular malformations in hereditary hemorrhagic telangiectasia: Doppler
      sonographic screening in a large family.
AB  - BACKGROUND/AIMS: The prevalence of hepatic vascular malformations in hereditary
      hemorrhagic telangiectasia has been estimated in the literature on clinical
      criteria, thus giving unreliable data. In our study the presence of hepatic
      vascular malformations in hereditary hemorrhagic telangiectasia was evaluated in
      a large Italian family by using Doppler sonography findings were compared to
      computed tomography and angiography results. Clinical features were related to
      the severity of hepatic vascular malformations. METHODS: Seventy-three relatives
      were checked for the presence of signs of hereditary hemorrhagic telangiectasia.
      Abdominal Doppler ultrasonography was performed in all of them. Every subject
      with a positive Doppler ultrasonography for hepatic vascular malformations
      underwent abdominal computed tomography and celiac angiography. RESULTS: Forty
      family members proved to be affected by hereditary hemorrhagic telangiectasia. Of
      these, hepatic vascular malformations were evidenced by Doppler ultrasonography
      in 13 females. Doppler ultrasongraphy demonstrated minimal hepatic vascular
      abnormalities in three subjects, moderate in three, and severe in seven. Doppler
      study was diagnostic for arteriovenous shunt with hepatic veins in seven cases
      and with portal vein in two. Computed tomography failed to demonstrate hepatic
      vascular malformations in two cases, while angiography confirmed the Doppler
      sonographic findings in all cases. Cholestasis was present in subjects with
      moderate and severe hepatic vascular malformations. CONCLUSIONS: Doppler
      sonography is the ideal imaging technique to screen hereditary hemorrhagic
      telangiectasia affected families for hepatic vascular malformations. These
      malformations do not appear to be age-dependent, but sex-dependent. Cholestasis
      is the main clinical sign, and it seems to correlate with the severity of hepatic
      vascular derangement.

PMID- 9148002
TI  - Long-term expression of the hepatitis B virus core-e- and X-proteins does not
      cause pathologic changes in transgenic mice.
AB  - BACKGROUND/AIMS: Chronic infections with the human hepatitis B virus can result
      in liver cirrhosis and primary hepatocellular carcinoma. The reasons for these
      long-term effects are unclear. The aim of this study was to generate transgenic
      mice expressing the HBV X- and c/e-gene under authentic and foreign promoter
      control and to test whether the respective gene products can cause pathologic
      effects during the lifespan of a mouse. Moreover, the temporal and the tissue
      specific regulation of the crucial HBV c/e-gene promoter was analyzed. METHODS:
      Eight transgenic mouse lines were generated. Four contained the c/e- and X-gene
      and two contained only the X-gene under authentic promoter control. Two lines
      expressed only the X-gene under control of the rat insulin promoter/enhancer.
      Gene expression was tested by protein and mRNA analyses. During an observation
      period of 2 years, mice were sacrificed and organs subjected to histologic
      examination. Mice expressing the X-gene in pancreatic beta cells were tested for
      the development of diabetes. RESULTS: In the liver, slight histopathologic
      alterations but no neoplastic changes could be observed in mice expressing the X
      gene. Activity of the c/e-gene promoter/enhancer was age dependent and was not
      restricted to hepatocytes. CONCLUSION: No evidence was obtained that long-term
      expression of the HBV c/e- and X-gene products can cause neoplasia during the
      lifespan of a mouse.

PMID- 9148003
TI  - Placebo-controlled trial of vaccination with hepatitis B virus surface antigen in
      hepatitis B virus transgenic mice.
AB  - BACKGROUND/AIMS: Treatment of hepatitis B virus carriers by vaccine containing
      hepatitis B surface antigen with Pre-S protein and HBsAg/ anti-HBs complex has
      been reported and these studies have constituted a new and promising concept for
      the treatment of HBV-carriers. The present communication, a placebo-controlled
      trial of vaccination in HBV-transgenic mice, was designed to examine the impact
      of vaccination using a high dose of HBsAg for a duration of 12 months to achieve
      further insights about the dose, duration and effectiveness of vaccine therapy.
      Another aim of this study was to analyse the mechanism underlying the antiviral
      and immunomodulatory potentiality of vaccine therapy in HBV-transgenic mice.
      METHODS: HBV-transgenic mice positive for HBV DNA, hepatitis B surface antigen
      and hepatitis B e antigen in sera received either HBV-vaccine containing HBsAg in
      complete Freund's adjuvant (CFA), intraperitoneally, once a month for 12
      consecutive months (vaccine recipients), or only CFA, intraperitoneally once in a
      month for 12 consecutive months (placebo recipients). Thirty-two vaccine
      recipient and 16 placebo-recipient HBV-transgenic mice were injected, checked and
      followed on a monthly basis for the entire duration of 12 months. RESULTS: Of the
      32 transgenic mice from the vaccine-recipient group, 25 became completely
      negative for HBsAg and 30 for HBeAg. Five mice developed anti-HBs in sera after
      the observation period of 12 months. Semiquantitative estimation of HBV DNA by
      polymerase chain reaction showed that vaccination resulted in a decrease of HBV
      DNA in sera. Placebo-recipient transgenic mice did not show any significant
      change in the titres of HBV markers after receiving 12 monthly injections of CFA.
      Interleukin-2 could be detected in sera from vaccine-recipient transgenic mice,
      but not in placebo-recipient transgenic mice. CONCLUSIONS: Vaccination with a
      high dose of HBsAg in adjuvant over a long period had a significant antiviral as
      well as immunomodulatory potential in HBV-transgenic mice. This inspires optimism
      that vaccine alone or in combination with antiviral agents can be used
      successfully for the treatment of human HBV-carriers.

PMID- 9148004
TI  - The role of bile salt composition in liver pathology of mdr2 (-/-) mice:
      differences between males and females.
AB  - BACKGROUND/AIMS: The mouse mdr2 gene encodes a P-glycoprotein expressed in the
      canalicular membrane of the hepatocyte. Mice in which this gene has been
      inactivated (mdr2 -/-) show a defect in biliary phospholipid and cholesterol
      secretion and develop non-suppurative cholangitis. We hypothesized that secretion
      of bile salts without lipids initiates this liver disease. METHODS: To delineate
      the pathologic process, mdr2 (-/-) mice were fed different bile salt-supplemented
      diets for 22 weeks after weaning. Aspects of liver pathology including
      eosinophilic bodies, portal inflammation, ductular proliferation, mitotic
      activity and fibrosis were semi-quantitatively scored. RESULTS: It was observed
      that liver pathology was more severe in female than in male mice when fed a
      purified control diet. This correlated with a more hydrophobic bile salt
      composition of female vs. male bile. When increasing amounts of cholate were
      added to the diet (0.01% and 0.1%), the secretion of taurocholate increased and
      this was accompanied by a more severe liver pathology. At the high dose of
      cholate (0.1%), the bile salt compositions of male and female mice became
      similar, as did the severity of the histological score. Addition of cholate to
      the diet did not induce liver pathology in (+/+) mice. Addition of
      ursodeoxycholate to the diet (0.5%) led to a near complete replacement of biliary
      bile salts by tauroursodeoxycholate and this reduced pathology and dissipated the
      difference between males and females. CONCLUSIONS: These observations support our
      hypothesis that liver pathology in the mdr2 (-/-) mouse is caused by bile salts
      and depends on the hydrophobicity c.q. cytotoxicity of biliary bile salts.

PMID- 9148005
TI  - Differential diagnosis of acute HBsAg positive hepatitis using IgM anti-HBc by a
      rapid, fully automated microparticle enzyme immunoassay.
AB  - BACKGROUND/AIMS: We determined the diagnostic significance of IgM anti-HBc by a
      rapid, fully automated microparticle enzyme immunoassay (IMx CORE-M) in acute
      HBsAg positive hepatitis. METHODS: We studied prospectively for at least 6 months
      100 patients with acute self-limited hepatitis B (group A) and 40 patients with
      acute hepatitis superimposed on histologically confirmed chronic hepatitis B
      (group B). On admission, all patients in group A were positive and those in group
      B were negative for IgM anti-HBc by a commercially available enzyme immunoassay.
      RESULTS: Based on the assay criteria, the rates of IMx CORE-M (> 1.2) positive
      serum samples on admission, 4, 12 and 24 weeks later were: in group A: 100%, 95%,
      72%, 44% and in group B: 20%, 27.5%, 17.5%, and 15%, respectively.
      Misclassification was observed in 20-27.5% of the acute on chronic hepatitis B
      cases. However, the mean IMx CORE-M index value was found to be significantly
      higher in group A during the whole follow-up. In particular, on admission the
      mean IMx CORE-M index value was 2.504 +/- 0.435 (range: 1.508-3.482) in group A
      and 0.747 +/- 0.346 (range: 0.062-1.384) in group B (p < 0.001). Discriminant
      function analysis showed that the cutoff level between the two groups for IMxCORE
      M index on admission was 1.5. Four to 12 weeks from admission, in the group with
      acute on chronic hepatitis B cases, 13 patients with HDV and/or HCV
      superinfection had significantly lower IMx-CORE M index values compared with 27
      patients with acute hepatitis due to exacerbation of chronic hepatitis B.
      CONCLUSIONS: IMx CORE-M appears to be an accurate diagnostic test to
      differentiate acute from acute on chronic HBsAg positive hepatitis, but the cut
      off level seems to be higher (1.5 instead of 1.2).

PMID- 9148006
TI  - Inhibition of biliary bicarbonate secretion in ethinyl estradiol-induced
      cholestasis is not associated with impaired activity of the Cl-/HCO-3 exchanger
      in the rat.
AB  - BACKGROUND/AIMS: Bicarbonate is a major component of bile salt independent bile
      flow, which is impaired in ethinyl estradiol (EE)-cholestasis. To examine this
      subject in EE-cholestasis, we studied: 1) basal and glucagon-stimulated biliary
      bicarbonate secretion both in vivo and in the isolated perfused rat liver (IPRL);
      2) H+/HCO-3 transport processes in isolated rat hepatocyte couplets. METHODS:
      Rats received EE (5 mg.kg b.w.-1) for 5 days. Intracellular pH (pHi) was measured
      (BCECF-AM) using a single-cell microfluorimetric setup. RESULTS: Bile flow was
      markedly (p < 0.01) decreased in EE-treated rats. Bicarbonate concentration in
      bile was decreased (p < 0.01) and bicarbonate secretion was 2.5-fold lower in EE
      treated animals than in controls, both in bile-fistula rats [19.5 +/- 5.1 (n =
      23) vs 54.2 +/- 5.7 (n = 20) nmol.min-1g liver-1; p < 0.01] and in the IPRL [11
      +/- 2 (n = 8) vs 24 +/- 3 (n = 8) nmol.min-1.g liver-1; p < 0.01]. In control
      IPRL, a bile/perfusate gradient for bicarbonate is maintained, while it is lost
      in EE-treated IPRL because of the lower bicarbonate concentration in bile.
      Glucagon stimulated bile flow and bicarbonate secretion to a similar extent in EE
      treated and control IPRL (+25% vs +23%). Resting pHi of EE-treated hepatocyte
      couplets was higher in comparison with controls in KRB [7.25 +/- 0.07 (n = 35) vs
      7.20 +/- 0.05 (n = 33); p < 0.02] but similar in Hepes [7.08 +/- 0.07 (n = 24) vs
      7.05 +/- 0.06 (n = 26)]. Basal activity of the Cl-/HCO-3 exchanger was similar in
      EE-treated and control hepatocyte couplets [H+ flux = 2.87 +/- 1.12 (n = 18) vs
      3.01 +/- 1.23 mM/min (n = 15)] and was stimulated to a similar extent by
      glucagon. Na+/HCO3-symport activity was increased in EE-treated hepatocyte
      couplets (p < 0.05) while the Na+/H+ exchanger was unchanged. CONCLUSIONS:
      Bicarbonate biliary secretion is markedly impaired during EE-cholestasis in
      association with a marked decrease of bile salt independent bile flow. However,
      the Cl-/HCO-3 exchanger and its hormonal regulation are normal, indicating that
      the lower bicarbonate excretion in EE-cholestasis is not due to a compromised
      activity of this anion exchanger. Since the bile/perfusate gradient for
      bicarbonate is dissipated in EE-treated IPRL, the impaired bicarbonate excretion
      could be caused by a reflux of biliary bicarbonate via leaky tight junctions.

PMID- 9148007
TI  - Hepatic stellate cells (Ito cells) but not collagen IV may partly be responsible
      for lower portal pressure after reversing secondary biliary cirrhosis in the rat.
AB  - BACKGROUND/AIMS: Chronic bile duct obstruction in the rat leads to biliary
      cirrhosis and portal hypertension. Biliary decompression with Rouxen-Y choledocho
      jejunostomy (RY) reverses most but not all of these changes. The aim of the
      present study was to determine whether hepatic stellate cells, as a main source
      of extracellular matrix proteins, participate in this process. METHODS: Sprague
      Dawley rats were allocated to one of three groups: Bile duct ligation (BDL) for 3
      weeks, BDL followed by RY and sham-operated animals as controls (SHAM). At the
      end of the experimental period, portal pressure was measured, livers subjected to
      random sampling and hepatocytes, bile ducts/ductules, hepatic stellate cells and
      collagen IV determined stereologically. Hepatic stellate cells and collagen IV
      were characterized immunohistochemically with an antibody against desmin and
      collagen IV, respectively. RESULTS: Volume fraction of hepatocytes decreased from
      65.6 +/- 5.3 in sham-operated animals to 27.9 +/- 8.8% in bile duct ligated
      animals (p < 0.05). In contrast, volume fraction of bile ducts/ductules increased
      from 0.4 +/- 0.2 in sham-operated animals to 25.3 +/- 8.6% in bile duct ligated
      ones; similarly, hepatic stellate cells increased from 0.4 +/- 0.2 in sham
      operated animals to 2.6 +/- 0.9% in bile duct ligated ones (p < 0.01) and
      collagen IV from 10.0 +/- 2.3 in sham-operated animals to 24.5 +/- 8.0% (p <
      0.01) in bile duct ligated animals. These changes were partially reversed by Roux
      en-Y choledocho-jejunostomy; hepatocytes, bile ducts/ductules, hepatic stellate
      cells and collagen IV averaging 54.8 +/- 13.1, 6.1 +/- 6.8, 1.6 +/- 0.6 and 14.5
      +/- 3.6%, respectively (p < 0.05 RY vs. BDL). Portal pressure in sham-operated
      animals, bile duct ligated animals and those with a Roux-en-Y choledocho
      jejunostomy averaged 13.4 +/- 0.7, 20.1 +/- 2.7 and 16.9 +/- 1.6 cm H2O,
      respectively, and correlated significantly with the volume fraction of hepatic
      stellate cells (rS = 0.96; p < 0.001) and less with collagen IV (rS = 0.61; p <
      0.007). However, by stepwise regression, collagen IV did not significantly add to
      the ability of the equation to predict portal pressure. CONCLUSIONS: These
      results lend further support to the notion that hepatic stellate cells are
      prominently involved in fibrogenesis and in the reversibility of these changes,
      but hepatic stellate cells do not completely revert to normal even 4 weeks after
      successful decompression. Furthermore, our data suggest that hepatic stellate
      cells may be related to maintenance of portal hypertension.

PMID- 9148008
TI  - Prevention of portal hypertension by propranolol and spironolactone in rats with
      bile duct ligation.
AB  - BACKGROUND/AIMS: It has been suggested that the early administration of
      propranolol (PR) and a low sodium diet may prevent the development of
      portosystemic shunts in animals with presinusoidal portal hypertension. Our aim
      was to study the hemodynamic effects of the early and chronic administration of
      PR and spironolactone (SPN), alone or in combination, in a model of hepatic
      fibrosis and sinusoidal portal hypertension induced in rats by bile duct
      ligation. METHODS: A blind study was performed in 40 Sprague-Dawley rats divided
      into four groups: placebo (PL), PR (75 mg/kg per day), SPN (100 mg/kg per day),
      and PR+SPN at the same doses. Drugs were administered by daily gavage over a 4
      week period as soon as bile duct ligation was performed. At day 28, the
      splanchnic and systemic hemodynamics (radiolabeled microspheres) were evaluated.
      RESULTS: a) Systemic hemodynamics: PR significantly reduced cardiac index and
      increased vascular resistance, SPN had no significant effect and PR+SPN
      significantly decreased mean arterial pressure. b) Splanchnic hemodynamics:
      portal venous pressure (PL: 15.5 +/- 1.5, PR: 14.8 +/- 1.0, SPN: 13.5 +/- 2.1,
      PR+SPN: 15.0 +/- 1.3 mmHg, p < 0.05) and portosystemic shunts (PL: 30 +/- 31, PR:
      13 +/- 14, SPN: 5 +/- 4, PR+SPN: 29 +/- 33%, p < 0.05) were significantly reduced
      in the SPN group; other hemodynamic parameters were not significantly altered. In
      multivariate analysis, the only determinant of portosystemic shunts was portal
      pressure but with a low R2 (0.2). CONCLUSIONS: In this model, the early
      administration of PR, alone or in combination with SPN, had no beneficial
      hemodynamic effects. On the other hand, SPN alone decreased portal pressure and
      prevented portosystemic shunts. Therefore, this drug may have beneficial effects
      in patients with early portal hypertension.

PMID- 9148009
TI  - L-ornithine vs. L-ornithine-L-aspartate as a treatment for hyperammonemia-induced
      encephalopathy in rats.
AB  - BACKGROUND/AIMS: The effect of L-ornithine (ORN) and L-ornithine-L-aspartate (OA)
      therapy on "extracerebral" nitrogen metabolism, brain metabolism and
      neurotransmission has been investigated in portacaval shunted rats with
      hyperammonemia-induced encephalopathy. METHODS: One day before ammonium-acetate
      infusion, a portacaval shunt was performed in three experimental groups: 1
      control rats, 2-ORN-treated rats and 3-OA-treated rats. Ammonium-acetate was
      given as an intravenous bolus injection (0.4 mmol.kg bw-1) followed by a constant
      infusion (1.9 mmol.kg bw-1.h-1) so that steady-state blood ammonia concentrations
      (500-800 microM) were obtained in the course of 5 h. After 1 h, ammonium-acetate
      infusion, either L-ornithine or L-ornithine-L-aspartate, was infused for the next
      4 h (3.0 mmol.kg bw-1.h-1) in the treated groups. The following parameters were
      measured: clinical grade of encephalopathy, EEG activity (n = 10 - 20/group),
      amino acids in plasma (n = 10 - 20/group) and brain dialysate (n = 5 - 9/group),
      and brain metabolites obtained by in vivo cerebral 1H-MRS (n = 4 - 6/group).
      RESULTS: ORN and OA treatment resulted in significantly lower blood (34% and 39%)
      and brain (42% and 22%) ammonia concentrations, significantly higher urea
      production (39% and 86%) and significantly smaller increases in brain glutamine
      and lactate concentrations than in controls. These changes were associated with a
      significantly smaller increase in clinical grade of encephalopathy in ORN- and OA
      treated rats, and a significant improvement in EEG activity in ORN-treated rats.
      OA-treated rats showed a significant increase in aspartate and glutamate
      concentrations in brain dialysate. CONCLUSIONS: The beneficial effects of both
      treatments on the manifestations of hyperammonemia-induced encephalopathy can be
      explained by a reduction in blood and brain ammonia concentrations. It is
      suggested that when OA is administered, the effect of ornithine is partly
      counteracted by aspartate, inducing high brain extracellular concentrations of
      the two excitatory amino acids glutamate and aspartate, and perhaps causing
      overstimulation of NMDA receptors.

PMID- 9148011
TI  - Low doses of insulin-like growth factor-I improve nitrogen retention and food
      efficiency in rats with early cirrhosis.
AB  - BACKGROUND/AIMS: In order to ascertain whether malnutrition is an early-onset
      feature of liver cirrhosis and whether the anabolic hormone insulin-like growth
      factor I (IGF-I) could be useful in the treatment of this complication, we
      analyzed the nutritional alterations present in rats with early-stage liver
      cirrhosis and the effects of IGF-I on nutritional parameters in these animals.
      METHODS: After a 24 h fast, a 15N-enriched diet was administered for 5 days to
      normal control rats and to cirrhotic rats receiving subcutaneous injections of
      vehicle (Group 1) or IGF-I, 2 micrograms.100 g bw-1.day-1, (Group 2) during the 5
      experimental days. 15N, a stable N isotope, was measured in biological samples by
      mass spectrometry. RESULTS: Compared with control rats, Group 1 animals showed
      significant reductions in N intake and food efficiency (p < 0.05, both). In
      addition, the weight of the gastrocnemius muscle, its total N content and the
      dietary N content of this muscle were significantly lower in Group 1 than in
      control animals (p < 0.05, all). In rats from Group 2, mean values of N intake,
      food efficiency, gastrocnemius N content and the amount of dietary N incorporated
      into this muscle were similar to those in control rats, and (with the exception
      of gastrocnemius N total content) significantly higher than those in non-treated
      cirrhotic rats (p < 0.05, all). CONCLUSIONS: A variety of nutritional
      disturbances were detected in rats from the early stages of liver cirrhosis. Low
      doses of IGF-I were found to reverse most of these changes. These results
      stimulate further studies to determine whether IGF-I might be useful in the
      correction of the malnutrition present in patients with liver cirrhosis.

PMID- 9148010
TI  - Impairment of metabolic hepatic nerve action by chronic but not acute ethanol
      intoxication studied in isolated perfused rat liver.
AB  - BACKGROUND/AIMS: Liver carbohydrate metabolism and blood flow are regulated by
      hepatic nerves and hormones such as glucagon, insulin or catecholamines. Acute
      and chronic application of alcohol are known to depress the function of central
      and peripheral nerves. The extent of inhibition of the autonomic nervous system
      is not well characterized; thus, the possible impairment of hepatic nerve
      function by acute and chronic application of ethanol was investigated. METHODS:
      Rat livers were perfused simultaneously via both the portal vein and hepatic
      artery. Hepatic nerves were stimulated electrically for 2 min (20 Hz, 20 V, 2
      ms). As a control, noradrenaline (1 microM) was infused into the portal vein for
      2 minutes. RESULTS: During acute application of ethanol in portal concentrations
      of 50, 150 and 300 mM, which elevated basal glucose release, stimulation of
      hepatic nerves as well as portal noradrenaline infusion caused the same increase
      in glucose output and decrease in portal and arterial flow as in controls.
      Following chronic application of ethanol by feeding rats the Lieber-DeCarli
      liquid diet containing 5% (v/v) ethanol for 4 and 6 weeks, only nerve stimulation
      caused a significantly reduced enhancement of glucose output (50%, p < 0.025),
      whereas portal noradrenaline was as effective as in controls. Noradrenaline
      overflow was significantly reduced following nerve stimulation. CONCLUSION: The
      decrease in nerve stimulation-dependent glucose output and noradrenaline overflow
      in chronically ethanol fed rats indicates an impaired function of hepatic nerves.

PMID- 9148012
TI  - Decrease in HDV endemicity in Italy.
AB  - BACKGROUND/AIMS: To evaluate a possible variation in hepatitis D virus endemicity
      in Italy, the data from a multicentre study concerning HBsAg chronic carriers
      first observed in 31 liver units during 1992 were compared with the corresponding
      figures from a similar study performed in 1987. METHODS/RESULTS: In both studies
      the methodology for the recruitment of cases was the same. The overall anti-HD
      prevalence in 1992 was 14.4%, a significantly lower rate than that observed in
      1987 (23.4%, p < 0.01). The decrease significantly (p < 0.01) affected both males
      and females; it occurred in all geographical areas, although to a greater extent
      in northern regions. It was evident in subjects below 50 years of age, but not in
      subjects older than 50. A significant reduction in the anti-HD prevalence was
      seen in all forms of chronic hepatitis. CONCLUSIONS: These findings indicate a
      lower level of hepatitis D virus endemicity in Italy, probably as a consequence
      of the reported decreased pool of HBsAg chronic carriers, the reduced size of
      families, the improved socio-economic conditions and changes in intravenous drug
      abuser behaviour. All these factors may have affected the strength of hepatitis D
      virus infection which has greatly reduced the spread of the virus.

PMID- 9148014
TI  - A case of pseudolymphoma of the liver with chronic hepatitis C.
AB  - A case of pseudolymphoma (reactive lymphoid hyperplasia) of the liver in a 72
      year-old male with chronic hepatitis C is presented. Imaging studies, comprising
      ultrasonography, computed tomography, incremental computed tomography, and
      magnetic resonance imaging, suggested hepatocellular carcinoma. A tumor-like
      lesion was therefore resected. Grossly, the lesion was relatively poorly defined
      and measured 15 x 17 mm; microscopically, it consisted of lymphocytic
      proliferations forming follicles comprising numerous germinal centers that were
      mainly composed of L-26 positive B-cell lymphocytes. The lymphocytes surrounding
      germinal centers were mainly UCHL-1 positive T lymphocytes. The B cells in the
      lymphoid follicles stained positive for both kappa and lambda light chains at
      sequential frequencies, indicating polyclonal and benign features. These findings
      suggest that the diagnosis of pseudolymphoma of the liver is tenable from imaging
      studies supplemented, when necessary, with biopsy. Further studies may provide
      insights into diagnostic strategies and the mechanism of stimulation in HCV
      infections.

PMID- 9148013
TI  - Transient inhibition by orotic acid does not abolish the in vivo response of rat
      hepatocytes to a direct mitogen, lead nitrate.
AB  - BACKGROUND: Orotic acid (OA) is able to inhibit hepatocyte proliferation in vivo
      induced by 2/3 partial hepatectomy. The present studies were aimed at
      establishing: (i) whether OA also inhibits hepatocyte proliferation induced by a
      direct mitogen and, if so (ii) whether the stimulus provided by the mitogen is
      still expressed following transient inhibition by OA. METHODS/RESULTS: In the
      first experiment male Wistar rats were injected with either lead nitrate (100
      mumol/kg, i.v.) or saline and 20 h later some animals receiving the mitogen were
      also implanted with a 400-mg OA tablet (as OA-methyl ester. i.p.). Multiple
      injections of 3H-thymidine were given to each rat (50 microCi each, 6 h apart,
      i.p.) until 2 h before killing. All groups were killed 3 days after the initial
      treatment. Results indicated that OA almost completely inhibited hepatocyte DNA
      synthesis and labelling induced by lead nitrate (e.g. labelling index was 1.9 +/-
      0.5% in the saline-treated group, 44.7 +/- 4.0% in the lead nitrate group and 1.4
      +/- 0.3% in the group receiving lead nitrate + OA). Based on the above results,
      in a second experiment rats were given a similar dose of lead nitrate and a
      subset of animals was implanted 20 h later with a 400-mg OA tablet, as previously
      described. Multiple doses of 3H-thymidine were again given to each rat (20
      microCi each, 6 h apart) until 2 h before killing. Animals from both groups were
      killed at 3, 6 or 8 days after lead nitrate. Results indicated that, while at day
      3 lead nitrate-induced DNA synthesis was effectively inhibited by OA, at day 6
      the proliferative response was resumed in the group receiving OA. Cumulative
      labelling index over 6 days was 30.3 +/- 1.4 in rats given the mitogen alone and
      52.1 +/- 2.2 in the group exposed to lead nitrate + OA. CONCLUSIONS: These data
      indicate that: (i) OA is also able to inhibit hepatocyte proliferation induced by
      a direct mitogen such as lead nitrate; this, in turn, suggests that its
      inhibitory effect is not unique to the stimulus elicited by partial hepatectomy.
      (ii) The proliferative response triggered by the mitogen is not abolished by the
      transient (3-4 days) inhibitory phase imposed by OA. Possible mechanisms
      underlying these effects are considered in the discussion.

PMID- 9148015
TI  - Images in hepatology. Hepatic abscesses in a patient with yersiniosis and iron
      overload.

PMID- 9148016
TI  - Presence of ATP-dependent copper transport in the hepatocyte canalicular membrane
      of the Long-Evans cinnamon rat, an animal model of Wilson disease.

PMID- 9148017
TI  - Risk factors for HCV infection.

PMID- 9148018
TI  - Does immunoglobulin interfere with the immunogenicity to Pasteur Merieux
      inactivated hepatitis A vaccine?
AB  - BACKGROUND/AIMS: The aim of this study was to compare the immunogenicity of
      Pasteur Merieux (P.M. s.v.) inactivated hepatitis A vaccine when given alone with
      its immunogenicity when given in combination with immunoglobulin. METHODS: We
      enrolled 80 healthy volunteers who were seronegative for anti-HAV. Forty subjects
      (group A) were given two doses of vaccine at 0 and 6 months plus 4 ml of
      immunoglobulin given simultaneously with the first vaccine injection; and 40
      subjects (group B) were given vaccine alone. The population characteristics (age,
      sex, height and weight) of the two groups were comparable. RESULTS: Anti-HAV
      antibody was detectable at week 1 in 100% of group A and in 5.7% of group B, and
      in 100% of both groups at 4 and 8 weeks. Seroconversion rates (> or = 20 mIU/ml)
      were 97.4% in group A and 100% in group B at week 24 and were 100% in both groups
      4 weeks after a booster injection at 6 months. The antibody response level was
      lower after concomitant administration of vaccine with immunoglobulin. The
      antibody geometric mean titer was higher at week 1 in subjects who had been given
      vaccine and immunoglobulin, but nearly 50% lower at week 4 and thereafter,
      indicating inhibition of the vaccine-induced immune response by immunoglobulin.
      At week 28, i.e. 4 weeks after the booster injection, geometric mean titers had
      increased about 13-15 times in both groups, reaching highly protective antibody
      levels (3351 mIU/ml in group A and 5843 mIU/ml in group B). No serious adverse
      effects were observed during the follow-up. CONCLUSIONS: These data indicate that
      P.M. s.v. hepatitis A vaccine is highly immunogenic and safe, even when given
      simultaneously with immunoglobulin. Despite the interference of the
      immunoglobulin with the active immune response, individuals who were immunized
      passively plus actively also developed high titers of anti-HAV antibody. It is
      therefore reasonable to expect that this inhibition will not affect the overall
      protection conferred by the vaccine.

PMID- 9148019
TI  - Anomalous expression of costimulatory molecules B7-1, B7-2 and CD28 in primary
      biliary cirrhosis.
AB  - BACKGROUND: T lymphocytes require two important signals for efficient activation:
      1) recognition of antigens bound to self major histocompatibility complex
      antigens, and 2) simultaneous stimulation via so-called costimulatory molecules.
      Interaction of the costimulatory B7 molecules on antigen presenting cells with
      CD28 on T lymphocytes appears to be particularly important, as it modifies
      secretion of cytokines, especially interleukin 2. In primary biliary cirrhosis
      biliary epithelial cells aberrantly express major histocompatibility complex
      class II antigens and may function as antigen presenting cells. METHODS: We
      studied expression of HLA-DR, B7-1, B7-2 and CD28 on cryostat liver sections in
      16 patients with primary biliary cirrhosis, three patients each with autoimmune
      hepatitis and primary sclerosing cholangitis and nine patients with chronic viral
      hepatitis (five hepatitis B, four hepatitis C) using mouse monoclonal antibodies
      in an indirect immunoperoxidase technique. RESULTS: In advanced primary biliary
      cirrhosis, HLA-DR was found on 57% of bile ducts, B7-2 on 5% of bile ducts, and
      B7-1 could not be detected on any bile duct. Neither B7-1 nor B7-2 was seen on
      bile ducts in the four patients with early primary biliary cirrhosis. HLA-DR+
      bile ducts also lacked expression of B7 molecules in autoimmune hepatitis. In
      contrast, HLA-DR, B7-1 and B7-2 were expressed simultaneously on professional
      antigen presenting cells such as macrophages in epitheloid granulomas.
      CONCLUSION: HLA-DR+ biliary epithelial cells in primary biliary cirrhosis
      insufficiently co-express B7-1 or B7-2 molecules. Therefore, they must either use
      different costimulatory molecules, or otherwise are deficient in lymphocyte
      activation. Since recognition of antigen in the absence of B7-CD28 interaction
      may lead to anergy of lymphocytes, this might contribute to the impaired cytokine
      secretion found in primary biliary cirrhosis.

PMID- 9148020
TI  - Actin is a target antigen of anti-neutrophil cytoplasmic antibodies (ANCA) in
      autoimmune hepatitis type-1.
AB  - BACKGROUND/AIM: Anti-neutrophil cytoplasmic antibodies (ANCA) are a group of
      autoantibodies first associated with Wegener's granulomatosis and microscopic
      polyangiitis. The significance of ANCA in autoimmune hepatitis remains uncertain;
      the nature of the antigen or antigens has not been defined yet. The purpose of
      this study was to identify the target antigen of ANCA in patients with autoimmune
      hepatitis. METHODS/RESULTS: Sera from 32 type-1 autoimmune hepatitis patients
      were used in the present study. ANCA were detected in 24 of 32 sera (75%). A
      diffuse cytoplasmic staining pattern (C-ANCA) was detected in 14 patients; the P
      ANCA pattern was observed in 10 patients. An extract of human neutrophils was
      prepared and subjected to SDS-PAGE and Western Blot analysis. A 43-kD dominant
      immunoreactive protein was found in 20 (63%) autoimmune hepatitis patients.
      Aminoacid sequence analysis of the 43 kD protein identified actin. Cytoplasmic or
      perinuclear staining pattern could be reduced after absorption of sera with actin
      and after removing anti-actin antibodies by affinity chromatography. This was
      observed for all C-ANCA and for 8 out of 10 P-ANCA. Moreover in double-staining
      indirect immunofluorescence, the same type of diffuse cytoplasmic staining was
      observed with autoimmune hepatitis-sera and anti-actin antibodies. In Western
      Blot analysis with actin, 17 (53%) patients gave a positive result, while 15
      (47%) patients had a positive actin-ELISA. CONCLUSION: This is the first report
      to identify the cytoskeletal protein actin as an ANCA antigen.

PMID- 9148021
TI  - Differences in the regulation of cytochrome P450 family members during liver
      regeneration.
AB  - BACKGROUND/AIMS: Cytochrome P450 enzymes (P450s) metabolise endogenous substances
      and a vast variety of drugs. Little is known about the regulation of P450s during
      pathophysiological conditions in the liver. Therefore we studied the regulation
      of P450 1A1, 1A2, 2E1 and 3A during liver regeneration after two-thirds
      hepatectomy. METHODS: Partial hepatectomy or sham surgery was performed in
      Sprague-Dawley rats. At different time points after surgery, microsomal proteins
      were isolated and the RNA was prepared. Northern blot analysis, Western blot
      analysis and enzyme assays for the different P450s were performed. RESULTS:
      Northern blot analysis showed a transient downregulation of cytochromes P450 1A2
      and 2E1 after hepatectomy, while the expression of cytochrome P450 3A remained
      unaffected. Western blot analysis of microsomal proteins showed that changes of
      the mRNA levels are not reflected in the protein level, most likely because the
      half-life of the P450 proteins in hepatocytes is long, and thus a transient mRNA
      downregulation has little impact on the total amount of protein detected.
      Differences in the regulation of the enzymatic activities were found for P450 1A2
      and 2E1. Interestingly, the metabolic activity of cytochrome P450 2E1 decreased
      dramatically post-hepatectomy, while the P450 2A1 activity remained unchanged.
      CONCLUSIONS: Regulatory mechanisms were found on the RNA level and by post
      translational mechanisms which downregulate P450 expression and activity during
      liver regeneration. These results indicate prolonged half-life of drugs during
      hepatocyte proliferation, and thus also have important implications for therapy
      in humans.

PMID- 9148022
TI  - Polymorphism in the cytochrome P450 2E1 gene and the risk of alcoholic liver
      disease.
AB  - BACKGROUND/AIMS: To study the genetic susceptibility to alcoholic liver disease,
      we investigated the association between genetic polymorphism in the cytochrome
      P450 2E1 gene and the occurrence of alcoholic liver disease. METHODS: Four
      previously described restriction fragment length polymorphisms (RFLPs) in the
      cytochrome P 450 2E1 gene were analyzed by restriction endonuclease (Dra I, Msp
      I, Pst I and Rsa I) digestion of polymerase chain reaction amplified DNA
      segments. Polymorphisms in these loci were compared to the occurrence of fatty
      liver, alcoholic hepatitis and liver fibrosis in 319 males comprising total
      abstainers, moderate alcohol consumers and chronic alcoholics. RESULTS: The
      allelic frequencies for each RFLP in this series were: 0.89 and 0.11 (Dra I),
      0.98 and 0.02 (Msp I) and 0.99 and 0.01 (Pst I and Rsa I). The distribution of
      the alleles did not vary significantly between the different consumption groups.
      The allelic frequencies among patients with fatty liver, alcoholic hepatitis or
      liver fibrosis were not significantly different from the allelic frequencies
      among patients with normal liver histology. Comparison of different genotypes
      among moderate alcohol consumers (n = 43) or chronic alcoholics (n = 243) with or
      without liver disease showed no statistically significant associations. However,
      the rare polymorphic (d2) allele in the Dra I RFLP was found slightly more often
      among moderate consumers as well as alcoholics with alcoholic liver disease.
      CONCLUSIONS: These results indicate that the Msp I, Pst I and Rsa I RFLPs were
      very rare in the Finnish population, suggesting at most minor contribution to the
      inherited susceptibility to alcoholic liver disease. Polymorphism in the Dra I
      locus was more common in this study population, but showed no statistically
      significant association with alcoholic liver disease.

PMID- 9148024
TI  - Early indicators of prognosis in fulminant hepatic failure: an assessment of the
      King's criteria.
AB  - BACKGROUND/AIMS: An accurate and early assessment of the individual patient is
      critical in deciding whether liver transplantation is indicated in the treatment
      of fulminant hepatic failure. Based on analysis of patients treated between 1973
      and 1985, the Liver Unit at King's College Hospital, London, developed a
      prognostic model to identify patients with a poor prognosis. The present study
      was done to determine the applicability of this model in fulminant hepatic
      failure patients seen at our center in the 1990s. METHODS: The records of 145
      patients with fulminant hepatic failure, treated conservatively at Queen
      Elizabeth Hospital, Birmingham between 1990 and 1994, were analyzed. An
      additional 81 patients, who were transplanted for fulminant hepatic failure
      during the same period were excluded from the study. RESULTS: Application of
      King's College Hospital criteria at the time of admission to this hospital in the
      acetaminophen group, had a positive predictive value of 88%, negative predictive
      value of 65% and predictive accuracy of 71%. The positive predictive value,
      negative predictive value and predictive accuracy of these criteria for non
      acetaminophen-induced fulminant hepatic failure, were 79%, 50% and 68%.
      Multivariate analysis identified prothrombin time, serum creatinine, white cell
      count and abnormal potassium levels as independent predictors of mortality in
      acetaminophen-induced fulminant hepatic failure; and prothrombin time alone in
      fulminant hepatic failure induced by other etiologies. CONCLUSIONS: The King's
      College Hospital criteria for predicting outcome of fulminant hepatic failure
      were found to have a slightly lower predictive accuracy than shown in the
      original study.

PMID- 9148023
TI  - Quasispecies nature of hepatitis C virus and response to alpha interferon:
      significance as a predictor of direct response to interferon.
AB  - BACKGROUND/AIMS: We evaluated the significance of the quasispecies nature of HCV
      as a predictor of the response to alpha interferon therapy in patients with
      chronic hepatitis C. METHODS: Natural alpha interferon was administered in 62
      patients for 24 weeks (daily for 2 weeks, then three times weekly for 22 weeks)
      and factors were analyzed that could affect the response. HCV subtype, HCV RNA
      concentrations and the number of HCV quasispecies were evaluated before
      treatment. HCV RNA concentrations were measured by branched DNA probe assay. The
      number of HCV quasispecies was measured by fluorescence single-strand
      conformation polymorphism analysis. RESULTS: The HCV RNA concentration (p <
      0.0001), HCV subtype (p = 0.0076), and the number of HCV quasispecies (p =
      0.0024) were significantly associated with a complete response. Multivariate
      analyses showed that the number of HCV quasispecies was an independent predictor
      of the disappearance of HCV RNA during the administration of alpha interferon,
      but did not predict a relapse after its completion. Pretreatment concentration of
      HCV RNA was the only factor that was related to a long-term disappearance of HCV
      RNA. CONCLUSIONS: The number of HCV quasispecies was significantly related to the
      response to alpha interferon early in its administration. The pretreatment
      concentration of HCV RNA was mainly related to a relapse following completion of
      treatment.

PMID- 9148025
TI  - Graft dysfunction following liver transplantation: role of free radicals.
AB  - BACKGROUND/AIMS: Following orthotopic liver transplantation primary graft non
      function occurs in about 10% of patients, and survival depends on early
      retransplantation. The aetiology has yet to be defined, but reperfusion injury as
      a result of free radical production has been considered as a possible mechanism.
      In this study we looked for evidence of free radical generation intraoperatively
      and assessed the relationship between free radical production and graft function.
      METHODS/RESULTS: Twenty-one patients (M:F 10:11, mean age; 53 +/- 3.8 years) who
      underwent liver transplantation for end-stage liver disease were studied. Free
      radical activity increased significantly following reperfusion, as shown by: (i)
      the diene conjugated method, where the percentage molar ratio increased from a
      baseline of 10.87 +/- 0.78% to 24.42 +/- 7.8% (p < 0.01), and (ii) by electron
      paramagnetic resonance, where a more than a twofold rise in radical concentration
      was detected (p < 0.05). The increase in free radical activity detected by the
      diene conjugated method was significantly higher in patients with poor outcome as
      compared with those who had uneventful recovery (p < 0.01). CONCLUSION: Free
      radical activity is increased following reperfusion of liver graft during
      transplantation, and the magnitude of the rise is related to the severity of
      graft dysfunction.

PMID- 9148026
TI  - Hyperdynamic circulation in patients with cirrhosis: direct measurement of nitric
      oxide levels in hepatic and portal veins.
AB  - BACKGROUND/AIMS: Peripheral vasodilation represents the main vascular dysfunction
      associated with the hyperdynamic circulation of liver cirrhosis. This study was
      intended to measure directly regional and systemic levels of nitric oxide, a
      potent vasorelaxing mediator, in order to assess its role in the development of
      hemodynamic changes of cirrhosis. METHODS: We compared nitric oxide levels in the
      splanchinic and systemic circulation of 25 patients with cirrhosis undergoing
      transjugular intrahepatic portosystemic stent shunt and in the hepatic vein and
      peripheral blood of 10 patients without cirrhosis submitted to venous
      catheterization. Nitric oxide levels were measured through electron paramagnetic
      resonance spectroscopy as nitrosylhemoglobin complexes. RESULTS: Significantly
      higher nitric oxide levels were calculated in patients with cirrhosis with
      respect to controls, both in the peripheral and hepatic veins. In patients with
      cirrhosis, nitric oxide levels in the portal vein (3.44 +/- 2.17, expressed in
      arbitrary units) were higher than in the systemic circulation (1.89 +/- 1.15),
      but lower than in the hepatic vein (4.75 +/- 2.53; p < 0.001 by variance
      analysis). CONCLUSIONS: These data suggest that nitric oxide synthetic pathway
      activity as well as nitric oxide release are enhanced at the level of splanchnic
      vasculature and, more important, in the hepatic tissue, confirming evidence of
      the predominant role of nitric oxide in the pathogenesis of hemodynamic changes
      in patients with cirrhosis with portal hypertension.

PMID- 9148027
TI  - Effect of bacterial lipopolysaccharide on endothelin-1 production in human
      vascular endothelial cells.
AB  - BACKGROUND/AIMS: The plasma levels of endothelin (ET) are 2-5 fold higher in
      patients with cirrhosis than in healthy subjects. It has been proposed that
      endotoxemia could be a mechanism responsible for this phenomenon. However,
      investigations in rats with cirrhosis indicate that a differential regulation for
      prepro ET-1 mRNA expression occurs in the liver tissue of these animals but not
      in the aorta or other organs. The aim of the study was to investigate the effect
      of bacterial lipopolysaccharide (LPS) on endothelin-1 synthesis and release in
      cultured human vascular endothelial cells (HUVEC). METHODS: Confluent HUVEC at
      passage levels 3 and 4 were exposed to increasing doses of LPS (1-1000 ng/ml) for
      4 h at 37 degrees C and prepro ET-1 mRNA accumulation and big ET-1 and ET-1
      concentrations in the conditioned medium were measured. RESULTS: Endotoxin had a
      dual effect on HUVEC. LPS at doses ranging between 250 and 1000 ng/ml induced a
      progressive diminution in ET-1 concentration in the culture medium. However,
      lower LPS concentrations dose-dependently increased big ET-1 and ET-1 release by
      HUVEC without altering prepro ET-1 mRNA expression. CONCLUSIONS: These results
      suggest that low LPS concentrations promote ET-1 release in HUVEC by a post
      transcriptional mechanism located upstream of big ET-1 in the biosynthetic
      pathway of ET-1. These findings could explain the existence of high circulating
      levels of ET-1 in cirrhosis in spite of transcriptional activation of prepro ET-1
      mRNA only occurring in the liver.

PMID- 9148028
TI  - Spontaneous bacterial peritonitis in patients with cirrhosis undergoing selective
      intestinal decontamination. A retrospective study of 229 spontaneous bacterial
      peritonitis episodes.
AB  - BACKGROUND/AIMS: Selective intestinal decontamination with norfloxacin is widely
      used to prevent spontaneous bacterial infections in cirrhosis. The study was
      performed to compare the spontaneous bacterial peritonitis occurring in patients
      with and without prophylactic norfloxacin. METHODS: Two hundred and twenty-nine
      consecutive episodes of spontaneous bacterial peritonitis, (193 in patients
      without (Group A) and 36 in patients with norfloxacin prophylaxis (Group B)),
      were retrospectively analyzed. In 100 episodes (86 and 14, respectively), the
      responsible organism was isolated in ascitic fluid. RESULTS: Clinical and
      laboratory data at diagnosis were comparable in both groups. There were marked
      differences (p < 0.001) between group A and B in the frequency of peritonitis
      caused by gram-negative (67.4% vs. 14.3%) and gram-positive (30.2% vs. 78.6%)
      bacteria. There were three polymicrobial episodes. Bacteria resistant to
      cefotaxime and gram-negative bacilli resistant to quinolones were isolated in
      ascitic fluid in nine (seven in Group A and two in Group B) and three episodes
      (all in Group A), respectively. No differences in the course of infection and
      patient survival were observed between groups. CONCLUSIONS: Spontaneous bacterial
      peritonitis in patients with and without prophylaxis with norfloxacin are not
      different in clinical features, response to treatment and prognosis. Spontaneous
      bacterial peritonitis caused by gram-negative organisms resistant to quinolones
      is extremely uncommon in patients with cirrhosis receiving prophylactic
      norfloxacin.

PMID- 9148030
TI  - Annual Congress of Dermatologic Research '97. Tours, France, April 10-11, 1997.
      Abstracts.

PMID- 9148029
TI  - Predictive value of serum sex hormone binding globulin for the occurrence of
      hepatocellular carcinoma in male patients with cirrhosis.
AB  - BACKGROUND/AIMS: The incidence of hepatocellular carcinoma is higher in males,
      presumably due to the influence of sex steroids. Therefore, to further assess the
      role of sex steroids in the occurrence of hepatocellular carcinoma, this study
      investigated the predictive value of different sex hormones and their binding
      protein. METHODS: Among 101 male patients with cirrhosis included in a
      prospective screening study, 29 developed hepatocellular carcinoma. We assessed
      the predictive value of 17 clinico-biological and 4 serum hormonal variables
      collected at enrollment, by the log-rank test and the Cox model. RESULTS: Age (p
      = 0.003), bilirubin (p = 0.04), sex-hormone-binding-globulin (p = 0.006) and
      albumin (p = 0.08) were predictive using the log-rank test, while estradiol and
      total and free testosterone were not. The Cox model showed age (p = 0.0003;
      relative risk = 7.52), sex-hormone-binding globulin (p = 0.001, relative risk =
      3.37) and albumin (p = 0.02, relative risk = 2.94) as the most predictive
      parameters. CONCLUSION: We conclude that high serum sex-hormone-binding-globulin
      levels have an independent predictive value for the occurrence of hepatocellular
      carcinoma. Serum sex-hormone-binding-globulin could be used to define patients at
      high risk for hepatocellular carcinoma and could hypothetically play a role in
      hepatocarcinogenesis.

PMID- 9148031
TI  - Preventing osteoporotic fractures with alendronate.

PMID- 9148032
TI  - Proceedings of the 3rd Workshop on the Biology of Neuroectodermal Tumours. Rome,
      Italy, June 12-14, 1995.

PMID- 9148033
TI  - [Drug interactions: I. General principles].

PMID- 9148034
TI  - [Symptomatic treatment of constipation].

PMID- 9148035
TI  - Anti-HIV antibody in saliva: an assessment of the role of the components of
      saliva, testing methodologies and collection systems.
AB  - The various components of saliva, namely mixed saliva, parotid saliva,
      submandibular saliva, crevicular fluid and minor (labial) gland secretions, were
      collected from 63 known HIV antibody seropositive patients. A commercial test
      system, Wellcozyme HIV 1+2, and an antibody capture ELISA (GACELISA), were
      compared for sensitivity against all components. Sensitivity of the GACELISA
      system was 100% in 123 mixed saliva, 121 parotid saliva and 127 labial fluid
      samples, and 98% in 99 submandibular samples and 127 crevicular fluid samples.
      Respective figures for Wellcozyme 1+2 were 92%, 55%, 73%, 66% and 63%. Mixed
      saliva was most easily, conveniently and effectively collected using a plain
      Salivette. In 241 Salivette samples examined from the 63 patients, GACELISA
      proved 100% sensitive, and Wellcozyme 95% sensitive. Another form of Salivette
      impregnated with citric acid was unsuitable for GACELISA and gave a false
      negative value of 45%. In 197 samples from the gingival margin taken by a dry
      swab, GACELISA showed a sensitivity of 98% and Wellcozyme 81%. The most sensitive
      method for demonstrating anti-HIV antibody in saliva is to collect mixed saliva
      with the plain Salivette system and assay anti-HIV antibody levels by GACELISA.

PMID- 9148036
TI  - Relationship of circulating CD4+ T-lymphocytes and p24 antigenemia to the risk of
      developing AIDS in HIV-infected subjects with oral hairy leukoplakia.
AB  - To investigate the relationship of circulating CD4+ T-lymphocytes and p24
      antigenemia to the development of AIDS in HIV-infected subjects with hairy
      leukoplakia (HL), we have followed over eight years 173 HIV-positive patients,
      all asymptomatic at the start of the study, and compared those who developed HL
      (n=55) to those who did not (n=118). Both groups included injection drug users
      (IDUs), homosexual men, and hemophiliacs. At the time of their first visit, both
      HL+ and HL- patients had a normal value of CD4+ cells and a low frequency of p24
      antigenemia. During the years of follow-up, patients in the HL+ group showed a
      greater reduction in CD4+ cells, a significant increase in p24 antigenemia, and a
      higher rate of progression to AIDS. Our study demonstrates that in HIV-positive
      patients, HL is associated with more compromised immunological parameters and a
      higher viral replication and that its appearance has a negative prognostic value
      in relation to AIDS progression.

PMID- 9148037
TI  - Heterogeneity of ICAM-1 expression, and cytokine regulation of ICAM-1 expression,
      in skin and oral keratinocytes.
AB  - Differences in expression of intercellular adhesion molecule-1 (ICAM-1) and ICAM
      1 mRNA levels were studied in cultured skin and oral keratinocytes before and
      after stimulation with different pro-inflammatory cytokines. Basal expression of
      ICAM-1 was undetectable on skin keratinocytes but oral keratinocytes expressed
      ICAM-1 at high levels. Interferon-gamma (IFN-gamma) and tumor necrosis factor
      alpha (TNF-alpha) increased ICAM-1 expression on both cell types, although TNF
      alpha had a greater effect on oral than skin keratinocytes (P<0.05) and IFN-gamma
      was more effective than TNF-alpha on both cell types (P<0.01). In combination,
      TNF-alpha and IFN-gamma synergistically increased ICAM-1 expression on skin
      keratinocytes only, although ICAM-1 mRNA was synergistically increased in both
      cell types. IL-1alpha and IL-1beta induced a small increase in ICAM-1 expression
      on oral keratinocytes but had no effect on skin keratinocytes.

PMID- 9148038
TI  - Sensitivity and specificity of OraScan (R) toluidine blue mouthrinse in the
      detection of oral cancer and precancer.
AB  - The efficacy of 1% toluidine blue in the identification of oral malignancies and
      potentially malignant oral lesions was evaluated among a group of Asian patients
      (n = 102) with undiagnosed oral mucosal lesions and conditions (n = 145). The
      trial, utilising a ready-to-use kit, was controlled by histopathologic evaluation
      of a total of 87 dye-retained or dye-negative lesions. Eighteen oral carcinomas
      all retained the dye and there were no false negatives, yielding a test
      sensitivity of 100%. Eight of 39 oral epithelial dysplasias were toluidine blue
      negative, giving a false negative rate of 20.5% and a sensitivity of 79.5% for
      oral epithelial dysplasias. The specificity of the technique was low (62%). Five
      dysplastic lesions were detected solely by the kit and this suggests that the
      method is valuable for surveillance of high-risk subjects in addition to its
      remarkable sensitivity in the detection of invasive carcinoma.

PMID- 9148039
TI  - Printing processes and printing inks, carbon black and some nitro compounds.
      Lyon, France, 10-17 October 1995.

PMID- 9148040
TI  - In the middle of the night: a psychosocial resource book for after hours.

PMID- 9148042
TI  - [Pia Dellson, a humanist who became a physician. The clinical eye stimulates the
      will "to be as wise as the other physician..."].

PMID- 9148041
TI  - [Recommendation from a SFOG working group: unified guidelines for IVF are
      needed].

PMID- 9148043
TI  - [The Dagmar fund--was it used correctly?].

PMID- 9148044
TI  - [An efficient health care needs more time for teaching and research].

PMID- 9148045
TI  - [Misleading marketing of bedside bacteriological diagnosis].

PMID- 9148046
TI  - [Legalized euthanasia is a devastating instrument in the hands of a single
      individual].

PMID- 9148047
TI  - [Risk of uncritically used echocardiography].

PMID- 9148048
TI  - [Pelvic dysfunction is an unknown concept for many physicians].

PMID- 9148049
TI  - [New trends in drug prescription are questioned].

PMID- 9148050
TI  - [Meetings on cost savings and techniques reduce time spent with patients!].

PMID- 9148051
TI  - [Professional secrecy and the new drug prescription formulary are not
      compatible].

PMID- 9148052
TI  - [Certain cases need prolonged thrombosis prophylaxis. Four studies on hip
      prosthesis are in concordance].

PMID- 9148053
TI  - [Hormone therapy in climacteric. Varying research results on risks and benefits].

PMID- 9148054
TI  - [Limited treatment of patients with poor prognosis. Discussion with relatives on
      life support care].

PMID- 9148055
TI  - [Laboratory medicine has a supportive function. Health care should benefit from
      competence].

PMID- 9148056
TI  - [Local agreements in health care are based on programs for mental illness. They
      stimulate measurements of quality and results].

PMID- 9148057
TI  - [Medical efforts during the Estonian ship wreck].

PMID- 9148058
TI  - [Psychosocial support activities. Care at the Sodersjukhuset].

PMID- 9148059
TI  - [Psychosocial support activities. Help to persons calling the Karolinska
      hospital's hotline].

PMID- 9148060
TI  - [Psychosocial support activities. Work at the crisis center in Uppsala].

PMID- 9148061
TI  - [Post-traumatic stress reactions among the survivors. Feeling of context is a
      protective factor when death is threatening].

PMID- 9148062
TI  - [Naval rescue workers and post-traumatic stress syndrome. Relieving conversation
      made coping easier].

PMID- 9148063
TI  - [P pills and APC resistance. General screening is not justified].

PMID- 9148064
TI  - [46 forensic psychiatric problems in cases of sexual abuse. Sex crime hysteria or
      public health problem?].

PMID- 9148065
TI  - [Universal autonomic ID-01 device for recording a dosage load on the patient].

PMID- 9148066
TI  - [A digital radiographic device for medical diagnosis].
AB  - The paper outlines a digital radiographic device which records radiation by
      scanning with a one-dimensional multiwire proportional chamber connected on-line
      to a computer. The device drastically reduces a dosage load on patients, improves
      the diagnostic potentialities of projectional radiography, yields quantitative
      diagnostic information, creates special diagnostic programmes, has fast-access
      and fire-safe archives. The device may be used for general-purpose radiographic
      examinations and it has advantages when used instead of conventional
      fluorographs.

PMID- 9148067
TI  - [A diagnostic-therapeutic complex with changeable structure].
AB  - The paper describes the principles in the construction of diagnostic and
      examining complexes which record biological potentials in the frequency range of
      0 to 20 kHz in real time and process them and, if required, either form the
      stimulating exposures or synchronize a recording process with external stimuli,
      as well as different purpose diagnostic and examining complexes designed by these
      principles. While solving different problems, the core of the complexes remains
      constant and only do the crate module ratio and attendant periphery change. The
      basic difference of the complexes is their software. The programme for
      examinations, processing of their results and creation of a database has a
      convenient interactive multi-window interface with an user.

PMID- 9148068
TI  - [Automated complex diagnosis and choice of treatment method in benign prostatic
      hyperplasia].
AB  - The paper deals with rational choice of conservative and surgical treatment of
      patients with benign prostatic hyperplasia (BPH), based on an automatic
      diagnostic approach and realization of four stages of a logistic model of choice
      of BPH treatment policy with individual features of the status of urological
      patients being borne in mind. The procedure was tested in 72 patients from a
      Voronezh regional clinical hospital of the South-Western Railway, in 92 patients
      from a Voronezh regional clinical treatment-and-diagnosis center. The values of
      informative parameters were obtained on the basis of computer-aided patients'
      self-testing, results of baseline examinations, up-to-date non-invasive studies
      of the prostate: urofluometry, ultrasound bilocation, MR tomography, etc. The
      findings lead to the conclusion that integration of computer technologies and up
      to-date medical equipment is promising for enhancing the quality of diagnosis and
      treatment of BPH.

PMID- 9148069
TI  - [A kit of disposable devices for transcutaneous puncture biopsy].
AB  - A kit of disposable devices has been devised for successful and safe puncture
      biopsy of abnormal formations deeply located in the lung, mediastinum, liver,
      breast, pleura. The use of the kit provides qualitative instant diagnosis, by
      decreasing the cost of studies, and rules out transmission of infections
      (hepatitis, AIDS), implantation of tumor cells into the puncture canal tissues,
      and reduces the incidence of traumatic pneumothorax and bleeding.

PMID- 9148070
TI  - [A set of devices for monitoring radon and thoron in various media].
AB  - A new class of devices has been designed for rapid and integral measurements of
      environmental radon and thoron at the levels much lower than the approved normal
      ones. The operation principle of the devices' transducers is based on deposition
      of ionized decay byproducts of radon and thoron onto the surface of a
      semiconductor detector in the measuring chamber, followed by recording of their
      alpha-radiation. The devised radiometers have some advantages, namely: a high
      sensitivity (10 Bk/m3), simultaneously record the air levels of radon and thoron
      in the spectrometric operation of measurements, require no changeable aerosol
      filters and potent air blowers. The available serial foreign analogues of
      radiometers have worse parameters and functional capacities than the designed PPA
      01M- and PPA-03 type ones.

PMID- 9148071
TI  - [Automated information retrieval system of the trauma physician].
AB  - The traumatologist's automatic information retrieval system (TAIRS) is a package
      of programmes and a database, which are implemented on the basis of informational
      models of mechanical and thermal injuries of the locomotor apparatus and
      hyperreactive adaptation syndromes in posttraumatic emergencies. TAIRS envisages
      operation in the following areas: 1) topometameric classification of locomotor
      mechanical injuries and recommendations on their treatment; 2) tabular models of
      hyperreactive adaptation syndromes and ways of their correction in posttraumatic
      emergencies; 3) terminological and eponymic glossaries.

PMID- 9148072
TI  - [Topological classification of mechanical injuries of the locomotor apparatus].
AB  - A topometameric classification of mechanical injuries of the locomotor apparatus
      has been developed specially for the traumatologist's automatic information and
      retrieval system (TAIRS). The classification is intended for formalized
      characterization of mechanical injuries. The purpose of making this formalized
      diagnosis of an injury is to obtain an injury code by which, on the basis of laid
      expert assessments, TAIRS gives recommendations how to treat a patient by taking
      into account the specialization of a health institution.

PMID- 9148073
TI  - [Computer simulation of post-traumatic emergency states].
AB  - The traumatologist's automatic informational and retrieval system permits one to
      make a diagnosis of injuries in a patient and to have recommendations on their
      treatment, as well as to analyze injury-related nonspecific adaptation syndromes
      of the locomotor apparatus, which are laid into the system of informational
      models.

PMID- 9148074
TI  - [Principles of designing feedback devices based on the theory of functional
      systems].

PMID- 9148075
TI  - [International Conference on Medical Instrument Engineering "Biomedinstrument
      96"].

PMID- 9148076
TI  - [Standardization of of instrumental tools for psychophysiological examinations].
AB  - The paper presents an approach to standardizing the methodical and technical aids
      used for qualitative and quantitative instrumental assessment of some human
      higher cortical functions in health and in disease. The formulated approach and
      some experience in developing and using instrumental tools to examine higher
      nervous performance enable one to define the basic characteristics and parameters
      to be standardized.

PMID- 9148077
TI  - [Use of a new exercise test in the early period of myocardial infarction:
      rationale and experience].
AB  - A new gradual exercise test (gravimetric test (GT)) has been proposed to use in
      early myocardial infarction (MI). GT is more physiologically and safe than a
      bicycle ergometry test, its sensitivity being 54.9%. The use of GT allows one to
      detect a group of patients with subsequent slower readaptation to exercises on
      post-MI days 7-10 and to make appropriate correction of treatment.

PMID- 9148078
TI  - [Measuring devices for determination of endurance and resistance of the
      periodontium to chewing loads].
AB  - Diagnostic measuring devices are presented to determine the endurance and
      resistance to vertical and horizontal loads. A variable capacitor is first used
      in the measuring units of the devices, which enhances the accuracy of their
      measurements and promotes efficient studies.

PMID- 9148079
TI  - [The AP-94 device for examination of ocular refraction].
AB  - The paper provides a brief account and technical data of an AP-94-type device (a
      refractometer) for examination of ocular refraction, which operates in the
      infrared spectrum and allows a correct diagnosis to be promptly and qualitatively
      established and corrective means to be chosen for the patient. The results of
      clinical tests of the device are given.

PMID- 9148080
TI  - [Paradigm of radiation-laser medical equipment and technology].
AB  - Based on quantum chemistry and chemical kinetics, the paper formulates basically
      new concepts of the possibility of controlling biochemical reactions in
      biological tissues by simultaneously making abnormal human visceral foci, in
      cancer diseases in particular, exposed to two rays via radiation and optic laser
      radiations. The paper also presents experimental findings of the channeling of X
      ray and fluxes of charged particles along the fiber wave guides. It considers the
      circuit engineering of a medical endoscopic device that concurrently transmits
      optic laser radiation and fluxes of penetrating radiation into the viscera.

PMID- 9148081
TI  - Exercise-induced death in sickle cell trait: role of aging, training, and
      deconditioning.
AB  - The pathophysiological process of exercise-induced death in subjects with sickle
      cell trait (SCT) remains unclear. Concerning the cause of death, authors have
      suggested stressful environmental conditions such as altitude, heat and humidity,
      or abnormal patient conditions such as deconditioning, fatigue, and disease.
      These conditions are thought to lead to hypoxemia, hyperlactatemia, acidosis,
      dehydration, hyperthermia, or exercise-induced rhabdomyolysis, all of which may
      initiate sickle cell crisis, disseminated intravascular coagulation,
      myoglobinuria, and renal failure. We report the case of a 41-yr-old, healthy, and
      apparently well-conditioned subject with SCT who died during a cross-country race
      under normal environmental conditions in good weather (in terms of temperature
      and humidity). The medical and athletic history of the subject were unremarkable.
      We refer to an epidemiological study that reported a relation between age and
      exercise-induced sudden death in subjects with SCT. We then review the
      pathophysiological effects of aging in association with deconditioning and high
      level training reported in the literature, particularly the decrease in aerobic
      metabolism in deconditioned subjects, and the exercise-induced hypoxemia in
      highly trained subjects. We discuss the consequences of deconditioning and high
      level training in subjects with SCT during exercise, and conclude that these
      factors may be involved in the age-dependent risk of exercise-related sudden
      death in subjects with SCT.

PMID- 9148082
TI  - Amenorrhea in ballet dancers in the Netherlands.
AB  - The prevalence of amenorrhea was studied among 113 professional and student
      ballet dancers in the Netherlands (mean age 23.3 yr, SD 4.8). Sixty-one dancers
      not on oral contraceptives were included in the subsequent analyses. Six cases
      (prevalence 9.8 percent, 95 percent confidence interval: 2.4-17.2) with secondary
      amenorrhea (< or = 4 cycles per year; previous menstruation > or = 3 months prior
      to the study; menarche > or = 1 yr prior to the study) were found. Two dancers
      had primary amenorrhea (no menarche at the age of > or = 16). There was a
      negative correlation between the age of menarche and the number of menstrual
      cycles during the 12 months preceding the study (r = -0.46, P = 0.001). Body
      composition (four-compartment model), amount of dancing (recorded), resting
      energy expenditure (ventilated hood), dietary intake (recorded), and indices of
      eating disorders (Eating Disorders Inventory, EDI) were studied in 15 of the
      dancers, 5 amenorrheic and 10 eumenorrheic. No significant differences were found
      between the amenorrheic and eumenorrheic dancers. An explanation for the lower
      prevalence of amenorrhea in ballet dancers in the Netherlands, compared with U.S.
      dancers, was not obvious. Relatively low EDI scores (25.8, SD 14.5) in a
      subsample of 24 dancers could indicate less rigid emphasis on leanness and
      dieting.

PMID- 9148083
TI  - Changes in physical strain and physical capacity in men with spinal cord
      injuries.
AB  - To determine longitudinal changes in physical capacity and physical strain during
      activities of daily living (ADL), 37 men with spinal cord injuries (C4/5-L5)
      performed an exercise test and various ADL on two occasions (T1 and T2; interval
      34.5 +/- 1.5 months). Parameters of physical capacity were aerobic power
      (VO(2peak)) and maximal power output (PO(max)). Physical strain was estimated by
      the heart rate response relative to the heart rate reserve. VO(2peak) at T2 (1.75
      +/- 0.55 1*min(1)) did not significantly differ from that at T1 (1.67 + 0.47
      1*min(-1)). Absolute PO max improved (P < 0.05) from 64.9 +/- 25.9 (T1) to 71.7
      +/- 27.2 W (T2), whereas relative PO(max) did not change. Activity level, time
      since injury, change in body mass, and occurrence of rehospitalization were the
      most important predictors of changes in physical capacity. Changes in relative
      VO(2peak) were related (P < 0.05) to changes in strain during transfers to the
      shower wheelchair (r = -0.39) and shower seat (r = -0.46), and during the curb
      ascent (r = -0.47). In conclusion, the hypothesized decline in physical capacity
      did not occur over the 3-yr period. Maintenance of physical capacity, which may
      in part be achieved through sport participation and improved medical care,
      together with avoidance of excessive body mass, may be useful to prevent high
      levels of strain during ADL.

PMID- 9148084
TI  - Physique as a risk factor for ulnar variance in elite female gymnasts.
AB  - The aims of this study were: 1) to determine ulnar variance variability of elite,
      female gymnasts; 2) to evaluate the relationship between ulnar variance and
      physique, maturity status, and training characteristics of these gymnasts. All
      156 skeletally immature female gymnasts were participants at the World
      Championships Artistic Gymnastics, Rotterdam, The Netherlands, in 1987.
      Chronological ages varied between 13.1 and 20.6 yr (mean = 15.9 +/- 1.3 yr). A
      large set of anthropometric dimensions was taken and somatotype was determined by
      the Heath-Carter technique. Skeletal age was assessed by the Tanner-Whitehouse II
      method. Menarcheal status and training data were collected by questionnaire.
      Ulnar variance was determined according to Hafner et al. Gymnasts differ
      significantly from reference girls with respect to physique and maturational
      status: gymnasts were smaller and delayed in skeletal maturity with about 1.5 yr.
      For those who had attained menarche, mean age at menarche was 15.1 +/- 1.3 yr.
      Ulnar variance shows a normal distribution in the gymnasts, ranging from -10.5 mm
      to +5.9 mm, which is somewhat more positive, i.e., an ulnar overgrowth, than
      reference wrists. The relationship between ulnar variance and somatic and
      maturational features suggests that female gymnasts who are more mature and have
      a physique characterized as relatively tall with a high lean body mass are at
      greater risk for developing a positive ulnar variance. No relationship between
      ulnar variance and training characteristics was evident. It is concluded that the
      observed positive ulnar variance in this sample of elite female gymnasts is less
      pronounced than originally stated in most "case reports."

PMID- 9148085
TI  - Historical and basic perspectives of SCUBA diving.

PMID- 9148086
TI  - Energetics of underwater swimming with SCUBA.
AB  - Underwater swimming has unique features of breathing apparatus (SCUBA), thermal
      protective gear, and fins. The energy cost of underwater swimming is determined
      by the drag while swimming and the net mechanical efficiency. These are
      influenced by the cross-sectional area of the diver and gear and the frequency of
      the leg kick. The speeds that divers can achieve are relatively low, thus the
      VO(2) increases linearly with values of VO(2)*d(-1) of 30-50 l*km(-1)for women
      and men, respectively. Diving experience had little effect on VO(2) for women;
      however, male divers with experience had lower VO(2) than beginners. The location
      and density of the gear can alter the diver's attitude in the water and increase
      the energy cost of swimming by 30 percent at slow speeds. The type of fin used
      has an effect on the depth and frequency of the kick, thus on drag and
      efficiency, with a range of VO(2) from 25 to 50 l*km(-1). A large flexible fin
      had the lowest energy cost and a large rigid fin the highest. Adding extra air
      tanks or a dry suit increased the cost of swimming by 25 percent. The energy cost
      of underwater swimming is influenced by gender, gear and its placement, fin type,
      and experience of the diver.

PMID- 9148087
TI  - Cardiovascular and thermal responses to SCUBA diving.
AB  - Recreational SCUBA diving exposes individuals to environmental stresses not often
      encountered in other types of activity. These stresses include increased ambient
      pressure, raised partial pressure of O(2), increased resistance to movement,
      added weight and drag of diving equipment, cold stress, and a higher breathing
      resistance. One means to understand how such stresses affect a diver is to employ
      the stress-strain-adaptive response model. Physiologic adaptations, like an
      increase in VO(2) in response to cold stress, will minimize the strain placed on
      thermal balance. Nonphysiologic adaptive responses include those behavioral and
      equipment interventions that isolate the diver from a particular stress. Self
      contained underwater breathing apparatus (SCUBA) isolates the diver from the
      inability to extract O(2) from the water; dive garments minimize the stress of
      cold water immersion. This review will focus on cardiorespiratory and thermal
      responses to SCUBA diving, using the stress-strain-adaptive response model to
      illustrate the interaction between diver and environment. Some responses like
      hyperventilation, cardiac arrhythmias, or cold injury due to vasoconstriction are
      not considered adaptive but are realistic possibilities in diving environments.

PMID- 9148088
TI  - Diagnosis and management of diving accidents.
AB  - Humans experience significant physiological stresses while diving, which can
      result in disease on occasion. With the increasing popularity of sports diving,
      it is critical that both physicians and divers be aware of the spectrum of
      illness associated with diving. An overview of common diving-related disorders is
      presented. After a brief discussion of relevant physics principles, the clinical
      presentation of ear and sinus squeeze is covered along with preventive strategies
      and treatment. This is followed by a discussion of the pathophysiology, clinical
      settings, and manifestations of pulmonary barotrauma along with a review of the
      pathophysiology and presentation of decompression illness. Initial emergency
      measures and referral procedures for decompression related disorders are
      addressed. A brief discussion of recompression therapy is included.

PMID- 9148089
TI  - Medical aspects of sport diving.
AB  - Medical issues in sport diving include illnesses that are caused by diving, and
      medical disorders that compromise safety. Cerebral air embolism and decompression
      sickness of the brain and spinal cord can result from diving. Sport divers may
      manifest a spectrum of symptoms from air embolism, which can range from
      unconsciousness to minimal symptoms, which include fatigue, personality change,
      poor concentration, irritability, and changes in vision. The physician must
      search for these minor symptoms in divers who are suspected of pulmonary
      barotrauma. Medical disorders of concern in diving include diseases of the lungs,
      the heart, the brain, and the endocrine system, particularly diabetes. Other
      factors involved in diving safety are exercise capacity and training. Clinical
      practice standards usually prohibit diving by individuals who have a seizure
      disorder that requires continuous medication. In the United States, we will not
      approve diving for individuals who have insulin-dependent diabetes or severe
      asthma. Some divers can return to diving after myocardial infarction or bypass
      surgery if they demonstrate good exercise tolerance and no ischemia on a graded
      exercise test, which simulates the physical activity needed for safe diving.

PMID- 9148090
TI  - The epidemiology of physical activity and physical function in older people.
AB  - A primary goal of studies of successful aging is to identify the modifiable
      factors related to the plasticity of higher physical function; however, little is
      known about the relationship between habitual physical activity (especially that
      of lower- to moderate-intensity) and the maintenance of day-to-day functioning in
      older people. The purpose of this paper is to address the question of how
      patterns of physical activity translate into altered physical function among
      healthy older populations. In this paper, physical activity is classified as a
      behavior, whereas physical function is classified as performance, comprised of a
      series of increasingly integrated steps. Recent data from several epidemiologic
      studies suggest that physical activity is associated with the maintenance of more
      basic components of physical function, as well as with higher-order task or goal
      oriented functions in healthy older people. Moreover, higher levels of physical
      activity appear to be associated with better functioning, even in those with
      already-existing chronic disease. Recent CDC/ACSM health recommendations call for
      incorporating at least 30 min of any activity into the daily schedule. Therefore,
      regular participation in activities of moderate intensity (such as walking,
      gardening, house/yard work) should be encouraged among the general older
      community.

PMID- 9148091
TI  - Maximal exercise hemodynamics and risk of mortality in apparently healthy men and
      women.
AB  - The purpose of this investigation was to determine the association of maximal
      exercise hemodynamic responses with risk of mortality due to all-causes,
      cardiovascular disease (CVD), and coronary heart disease (CHD) in a population of
      apparently healthy individuals. Study participants were 20,387 men (mean age =
      42.2 yr) and 6,234 women (mean age = 41.9 yr), patients of a preventive medicine
      center in Dallas, TX, examined between 1971 and 1989. Maximal heart rate and
      maximal systolic blood pressure (SBP) measured during the maximal exercise test
      were related to risk of all-cause, CVD, and CHD mortality. During an average of
      8.1 yr of follow-up, there were 348 deaths in men and 66 deaths in women. Among
      men, after adjustment for confounding variables, risks (and 95 percent confidence
      interval (CI)) of all-cause mortality for quartiles of maximal SBP, relative to
      the lowest quartile, were: 0.96 (0.70-1.33), 1.36 (1.01-1.85), and 1.37 (0.98
      1.92) for quartiles 2-4, respectively. Similarly adjusted risks for maximal heart
      rate were: 0.61(0.44-0.85), 0.69 (0.51-0.93), and 0.60 (0.41-0.87). Similar
      results were seen for risk of CVD and CHD death. In women, similar trends in
      adjusted risks of all-cause and CVD mortality across maximal SBP and heart rate
      categories were observed. For maximal heart rate, a 35 bpm higher value was
      associated with a 36 percent decreased risk of CVD mortality in men (RR = 0.63,95
      percent CI = 0.34-0.71) and an 8 percent lower risk in women (RR = 0.92,95
      percent CI = 0.18-4.63). These results suggest that an exaggerated SBP or an
      attenuated heart rate response to maximal exercise may indicate an elevated risk
      for mortality in this apparently healthy population.

PMID- 9148092
TI  - Age, fat-free weight, and isokinetic peak torque in high school female gymnasts.
AB  - The purpose of this study was to examine the covariate influence of fat-free
      weight (FFW) on age-related increases in isokinetic peak torque for leg flexion
      and extension in high school female gymnasts. Seventy-two gymnasts (X age +/- SD
      = 15 7 +/- 1.2 yr) volunteered to be measured for isokinetic leg flexion and
      extension strength using a calibrated Cybex II dynamometer at 30, 180, and 300
      degrees*s(-1) as well as for body composition from underwater weighing. The
      results indicated that there were significant (P < 0.05) zero-order correlations
      for age versus leg flexion (r = 0.36-0.47) and extension (r = 0.51-0.57) peak
      torque, as well as FFW versus leg flexion (r = 0.50-0.66) and extension (r =
      0.620.73) peak torque. There were also significant (P < 0.05) first-order partial
      correlations between age and peak torque (covaried for FFW) for leg extension at
      30 (r = 0.25), 180 (r = 0.36-0.39), and 300 degrees*s(-1) (r = 0.25-0.28) but not
      for leg flexion. These findings indicated that for the high school female
      gymnasts in the present study, there were age-related increases in strength that
      could not be accounted for by changes in FFW. It is possible that factors such as
      an increase in muscle mass per unit of FFW and/or neural maturation contribute to
      strength increases during adolescence in female athletes.

PMID- 9148093
TI  - Comparison of critical speed determined from track running and treadmill tests in
      elite runners.
AB  - The purpose of this study was to compare critical speed determined from a field
      test of maximal effort runs between 3 and 15 min on a running track and a
      laboratory test of high-speed runs on a treadmill with a 10-km criterion
      performance. Nine highly trained male runners (VO ++(2max) 67.7 +/- 4.1
      ml*kg*min(-1)) participated in the study. Critical speed was determined from
      three maximal runs (907, 2267.5, and 4081.5 m) on a 453.5-m indoor running track
      and from three high speed runs on a treadmill. The treadmill speeds were
      individualized so that exhaustion was reached in approximately 3, 7, and 13 min.
      All subjects participated in a 10-km cross-country race (measured distance 9.8
      km) on a flat and dry course. Track critical speed (293 m*min(-1)) was correlated
      (r = 0.92, P < 0.001) with race speed (293 m*min(-1)), whereas treadmill critical
      speed (300 m*min(-1)) had the same correlation but over predicted race
      performance. It was concluded that although both tests were correlated with 9.8
      km race performance, track-determined critical speed was easy to administer with
      highly trained runners and was very similar to 10-km race speed.

PMID- 9148094
TI  - Life adjustment correlates of physical self-concepts.
AB  - This research tested relationships between physical self-concepts and
      contemporary measures of life adjustment. University students (119 females, 126
      males) completed the Physical Self-Perception Profile assessing self-concepts of
      sport competence, physical condition, attractive body, strength, and general
      physical self-worth. Multiple regression found significant associations (P < 0.05
      to P < 0.001) in hypothesized directions between physical self-concepts and
      positive affect, negative affect, depression, and health complaints in 17 of 20
      analyses. Thirteen of these relationships remained significant when controlling
      for the Bonferroni effect. Hierarchical multiple regression examined the unique
      contribution of physical self-perceptions in predicting each adjustment variable
      after accounting for the effects of global self-esteem and two measures of social
      desirability. Physical self-concepts significantly improved associations with
      life adjustment (P < 0.05 to P < 0.05) in three of the eight analyses across
      gender and approached significance in three others. These data demonstrate that
      self-perceptions of physical competence in college students are essentially
      related to life adjustment, independent of the effects of social desirability and
      global self-esteem. These links are mainly with perceptions of sport competence
      in males and with perceptions of physical condition, attractive body, and general
      physical self-worth in both males and females.

PMID- 9148095
TI  - Multivariate allometric scaling of men's world indoor rowing championship
      performance.
AB  - The World Indoor Rowing Championship (WIRC) is based on the time (T) to row a
      simulated 2500 m on a rowing ergometer. In the WIRC there are separate age
      categories but only two weight classes: light and heavyweight, thus penalizing
      those just heavier and those significantly lighter than the cut-off weight.
      Multivariate allometric scaling (MAS) provides an expression of performance free
      of the confounding effect of more than one scaling variable. We used MAS to scale
      T by height (H) and age (A) to create a new index of rowing performance, T*H(
      a)*A(-b). Subjects were 148 male competitors from the 1995 WIRC. MAS indicated
      that T*H*A(-0.06) expresses T free of the confounding effect of H and A. We also
      scaled T only by H on those subjects, A < 40, (N = 109). Results showed that T*H
      is an optimal and particularly feasible scaling of T. Use of either convention
      dramatically changed race results. In conclusion, we recommend use of either the
      T.H (17 < or = A < or = 39) or T*H*A(-0.06) conventions to adjust WIRC
      performance in adult males.

PMID- 9148096
TI  - Single-subject methodology: an alternative approach.
AB  - The purpose of this paper is to identify and discuss an alternative experimental
      methodology, single-subject (SS) design. The primary premise for SS analyses
      forms the basis for many research questions in areas such as movement/motor
      control, individual performance patterns/strategies, and injury mechanisms. A
      brief historical perspective elucidating the evolution of modern-day group
      statistical techniques and the relationship to the individual is presented.
      Rationale for the SS design within this context is also discussed. Specific
      statistical applications include mean comparison tests (ANOVA, Model Statistics),
      correlation, and multiple regression. Validation of the underlying statistical
      assumptions of independence and normality relative to the applications are
      briefly discussed. Finally, several examples are included.

PMID- 9148097
TI  - Free flap monitoring: a review of current practice.
AB  - Individual techniques for the postoperative monitoring of free flaps vary
      considerably. In order to establish the currently preferred protocols, a survey
      was conducted among micro-surgeons in North America using a mailed questionnaire.
      Data were received from 95 centers for the monitoring of 2,825 free flaps
      performed during 1994. Results indicate that rates for flap salvage and overall
      success with free tissue transfer are closely related to surgical experience
      (number of cases performed per month). Ninety percent of microsurgeons routinely
      use monitoring devices, with external and laser doppler having achieved greatest
      popularity. An account is given of the preferred postoperative regimens for flap
      surveillance, and the overall results are discussed.

PMID- 9148098
TI  - Simple monitoring technique for muscle flaps.
AB  - A simple monitoring technique for the detection of postoperative arterial flow
      failure in muscle flaps is described. The technique consists of isolating a
      musculocutaneous perforator on elevation of a muscle flap. This cutaneous
      perforator is observed for pulsation in the postoperative period. Abrupt
      cessation prior to 48 hours should be an indicator for prompt clinical evaluation
      of the muscle flap by an experienced microsurgeon to rule out arterial
      thrombosis.

PMID- 9148099
TI  - Application of different types of free foot flaps in hand surgery.
AB  - From 1987, nine types of free vascularized flaps or combined flaps from the foot
      were used to treat 26 cases of hand injury with tissue loss. They were: (1)
      combined flap of 4 toe dorsums, big toe pulp, first toe web, and dorsalis pedis
      flap with long extensor tendons of the toes, (2) composite skin flap with the
      second metatarsophalangeal joint, (3) wrap-around flap from the great toe, (4)
      first toe web flap, (5) toe pulp flap with only an artery and a nerve, (6) wrap
      around flap of the great toe with a dorsalis pedis flap, (7) second toe with
      dorsalis pedis flap, (8) dorsalis pedis flap, and (9) first toe web flap with
      second metatarsal bone. All flaps survived. All the patients have used their
      reconstructed hand. Of the final motor functions of the reconstructed hands,
      68.8% are excellent, 27.3% are good, 3.9% are fair. Of the final cosmetic results
      of the reconstructed hands, 76.9% are excellent, 15.3% are good, 7.8% are
      acceptable. Of the patients, 64.9% are satisfied with the final results of the
      donor sites, 31.2% feel it is acceptable, and 3.9% feel it is unsatisfactory. The
      selection, indication, merits and demerits of vascularized foot flaps and
      attentive points in the operations are discussed in this paper.

PMID- 9148100
TI  - Eight years experience in crush and avulsion type finger amputation.
AB  - Between July 1986 and July 1994, we studied 125 total finger amputations due to
      crush and avulsion type injuries at the Izmir Hand and Microsurgery Hospital. Of
      the 125 fingers replanted, 88 were successful, for a general survival rate of
      70.4%. In the period between 1986 and 1991, we performed end-to-end anastomoses
      and achieved a survival rate of 48.3% (Group I). Between 1991 and 1994, with the
      application of a primary interpositional vein graft for the required indications
      in this type of injury, the general survival rate increased to 77.1% (Group II; P
      < 0.05). We conclude that the significant increase in the survival rate in Group
      II is related to both the increased experience of the surgical team and the
      application of the primary interpositional vein graft.

PMID- 9148101
TI  - Role of the perforating vein in vascular pedicle of free forearm flap.
AB  - An innovation in the preparation of the vascular pedicle of the free radial
      forearm flap is presented. While the radial artery is commonly used as the
      arterial pedicle of the flap, either the cutaneous venous system or the radial
      comitant vein (deep venous system) is used as the venous pedicle. The perforating
      vein communicates between these two venous systems at the cubital fossa, and we
      confirmed its presence in all but one of more than 180 cases. When the vascular
      pedicle is dissected proximally to the perforating vein contained in the flap,
      the venous drainage of both the deep and cutaneous systems can be restored by
      anastomosis of only one vein: the cutaneous or the radial comitant vein. On the
      other hand, the flap can be raised with the radial vessels (without the cutaneous
      vein) at the start of surgery, and a large caliber cutaneous vein, such as the
      median cubital, the cephalic, or the basilic, can be used for anastomosis in
      cases where the cutaneous veins in the distal forearm are too thin, or where the
      radial comitant vein is composed of two thin separated veins. We believe that
      preserving the perforating vein would make the forearm flap more reliable and
      more convenient in reconstructive surgery.

PMID- 9148102
TI  - Microsurgery without a microscope: laboratory evaluation of a three-dimensional
      on-screen microsurgery system.
AB  - In microvascular surgery, procedures may be both technically and physically
      demanding. Precise movements sustained over long hours in addition to typically
      compromised surgeon and assistant positioning lead quickly to physical and mental
      fatigue. Many of the positioning problems encountered are related to the fact
      that the eyes of the surgeon must be continually fixed to the microscope
      eyepieces. This study explores a possible solution: a microscope system that
      eliminates the need to view the operative field through the microscope eyepieces.
      A Three-dimensional On-screen Microsurgical System (TOMS) was used and contrasted
      with conventional operative microvascular surgery in the laboratory setting. The
      surgeon's comfort, his ability to instruct microsurgical technique, pertinent
      technological performance, and the procedure itself were evaluated using a
      standardized questionnaire. Based on data collected in this study, we conclude
      that divorcing the surgeon's eyes from the microscope eyepieces using the TOMS
      may make prolonged microvascular procedures less physically demanding and may
      increase the comfort level of both the surgeon and his assistant, although
      refinements to the technology are required.

PMID- 9148103
TI  - Vein-graft wrapping for the treatment of recurrent compression of the median
      nerve.
AB  - Recurrent compressive neuropathy of the median nerve due to cicatrix is an
      extremely challenging clinical problem. Available treatment techniques are
      difficult and results uncertain. Early experience with the autogenous vein graft
      wrapping technique has shown great promise for the treatment of chronic
      compressive neuropathy after other procedures have failed. We report on 3
      patients with average follow-up of 2 years. Postoperatively, all the patients had
      significant improvement on electromyograms, and the findings of both subjective
      and objective assessments were excellent or good for 2 patients. The procedure is
      simple; the donor is readily available; no complications were noted in the donor
      area, and the graft tissue has good compatibility. This technique can also be
      applied for chronic compression of any peripheral nerve.

PMID- 9148104
TI  - Effect of phosphate concentration in buffered irrigating solutions on arterial
      thrombosis.
AB  - The concentration of phosphate in buffered saline irrigation solutions was
      evaluated for its effect upon the incidence of arterial thrombosis. A rabbit
      thrombosis model of combined intimal abrasion and twisted pedicle in the rabbit
      central ear artery was used. Higher concentrations of phosphate (20 mM) in normal
      saline yielded a lower thrombosis rate at 7 days postoperatively (50%) in
      comparison to 5 mM phosphate (89% thrombosis rate; P < 0.05). A standard
      phosphate-buffered salt solution (Dulbecco's; 9.5 mM phosphate with potassium,
      calcium, and magnesium salts) also had a high thrombosis rate (91%). This study
      demonstrates that subtle variations in the irrigation solution can have profound
      effects upon arterial thrombosis.

PMID- 9148105
TI  - New model for microsurgical training and skills maintenance.
AB  - PracticeRat (Sharpoint, Reading PA) is a system containing a simulation vein,
      artery and nerve, designed as an alternative to live animal use in microsurgical
      training. We find PracticeRat to be more expensive than living models. However,
      it does decrease animal usage and provides a very convenient opportunity to
      practice microsurgical techniques and procedures in a fairly realistic manner.
      Trainees can practice anytime, for any length of time, wherever microscopes are
      available. In this regard we find PracticeRat+ to be a useful addition to
      microsurgical training programs and an excellent tool for skills maintenance.

PMID- 9148106
TI  - Improved early contour of free muscle flaps in extremity reconstruction.

PMID- 9148107
TI  - Rat strain differences in flap tolerance to ischemia.
AB  - The rat epigastric island flap model is commonly used to explore ischemia-related
      phenomena. We sought to evaluate strain differences in tolerance to ischemia
      using two commonly used rat strains: Sprague-Dawley and Lewis. Epigastric flaps
      (3 x 6 cm) based on the superficial epigastric artery and vein were raised
      bilaterally in each rat (2 flaps/rat). Ischemia was induced for 10,12,14, or 16
      hours by placing temporary occlusion clamps on each vessel of the vascular
      pedicle. Surviving flap areas were assessed planimetrically after 7 days. The
      average area of surviving flap tissue was greater in the Lewis rats for all
      ischemia times; this achieved significance for 12 hours and 14 hours of ischemia
      (P < 0.005). These findings indicate that comparisons among studies on rat flap
      ischemia must take into account the particular strain used. Furthermore, these
      findings suggest an inherent capacity of Lewis rat tissue to withstand ischemia
      better than tissue of the Sprague-Dawley rat strain.

PMID- 9148108
TI  - Kinetic aspects of macromolecular crystallization.

PMID- 9148109
TI  - [Epidemiology of musculoskeletal disorders caused by biomechanical overload
      (WMSDs)].
AB  - The link between occupation and musculo-skeletal disorders has been focused on in
      numerous research projects, ranging from those simply observing the different
      pathological findings reported among workers performing particular tasks, down to
      the latest studies actually quantifying the "exposure" of workers to physical and
      psycho-social stimuli, Recently, Hagberg et al (11) carried out a critical review
      of the literature concerning the upper limbs. For some disorders and certain
      tissues, the authors reported that specific types of work-related exposure are
      associated with the development of musculo-skeletal pathologies, and that the
      relative risks for certain types of occupational exposure can be extremely high.
      This has been proven in relation to tendinitis of the shoulder and hand-wrist,
      carpal tunnel syndrome, and tense neck syndrome, as well as several localised
      aspecific musculo-skeletal symptoms, such as pain. For other pathologies, the
      study reported contradictory results. This is the case for lateral epicondylitis,
      narrow chest syndrome and cervical radiculopathy. Associations have moreover been
      observed between several groups of disorders and certain psycho-social factors
      (e.g. workload, degree of discretionality).

PMID- 9148110
TI  - [Occupational risks and repetitive strain injuries in the Italian legislation].
AB  - Based on the experience gained from several criminal proceedings handled by the
      Public Prosecutor's Office in Turin, the author presents and discusses the
      Italian legislation covering the prevention of musculo-skeletal pathologies of
      the upper limbs in the workplace. In particular, the author examines the
      obligations associated with issuing medical reports on such disorders, and
      focusses attention on the obligations of the employer with respect to prevention
      (i.e. technical, organisational and procedural measures), monitoring employee
      health and the provision of training and information for employees in the light
      of both existing legislation (Italian Civil Code, DPR 303/56 and DPR 1124/65) and
      more recent regulations (D. Lgs. 626/94).

PMID- 9148111
TI  - [Proposal of a concise index for the evaluation of the exposure to repetitive
      movements of the upper extremity (OCRA index)].
AB  - In the light of data and speculation contained in the literature, and based on
      procedures illustrated in a previous research project in which the authors
      describe and evaluate occupational risk factors associated with work-related
      musculoskeletal disorders of the upper limbs (WMSDs), this article proposes a
      method for calculating a concise index of exposure to repetitive movements of the
      upper limbs. The proposal, which still has to be substantiated and validated by
      further studies and applications, is conceptually based on the procedure
      recommended by the NIOSH for calculating the Lifting Index in manual load
      handling activities. The concise exposure index (OCRA index) in this case is
      based on the relationship between the daily number of actions actually performed
      by the upper limbs in repetitive tasks, and the corresponding number of
      recommended actions. The latter are calculated on the basis of a constant (30
      actions per minute) which represents the action frequency factor, and is valid
      hypothetically-under so-called optimal conditions; the constant is diminished
      case by case (using appropriate factors) as a function of the presence and
      characteristics of the other risk factors (force, posture, complementary
      elements, recovery periods). Although still experimental, the exposure index can
      be used to obtain an integrated and concise assessment of the various risk
      factors analysed, and to classify occupational scenarios featuring significant
      and diversified exposure to such risk factors.

PMID- 9148112
TI  - [Clinical studies in working populations: a model for the anamnestic
      investigation of the pathology of the upper limbs and its practical application].
AB  - Following a brief review of the principal clinical characteristics of musculo
      skeletal disorders of the upper limbs, the authors propose a protocol for a
      structured anamnestic examination featuring a series of set questions. The
      anamnestic model is based on a detailed listing of the symptoms to be analysed,
      which are divided into four categories: pain, paraesthesia, symptoms attributable
      to hyposthenia, and neurovegetative disorders. Regarding pain and paraesthesia,
      the authors list the localisation, pattern of onset, duration and number of
      episodes, irradiation, and treatment. The patients can thus be classified as
      anamnestic cases based on the following criteria: presence of pain or
      paraesthesia during the last 12 months, with episodes lasting for at least one
      week, or occurring at least once a month, with no previous acute trauma. For
      hyposthenia, the authors report on the conditions under which the disorder may
      develop. The neurovegetative disorders considered are modifications in colour of
      the fingers and reaction to exposure to low temperatures. The structure of the
      proposed anamnestic chart permits all findings to be easily encoded for
      subsequent storage in a dedicated database. The Appendix contains an annotated
      facsimile of the anamnestic chart.

PMID- 9148113
TI  - [Clinical studies in working populations: value and significance of anamnestic
      findings, clinical tests and instrumental tests for the diagnosis of
      musculoskeletal disorders of the upper extremities].
AB  - The authors discuss the value and significance of symptoms in WMSDs, considering
      that the anamnestic threshold proposed in epidemiological investigations cannot
      be used as clinical and diagnosing criteria. Some useful clinical procedures are
      suggested for cases where there is a suspicion of musculo-skeletal disorders of
      the cervical spine and upper limbs, bearing in mind that they are to be applied
      within the framework of health surveillance programmes undertaken by health care
      practitioners who are not specialists in orthopaedics, physiatrics or neurology.
      The recommendations for instrumental tests and specialist referrals are also
      discussed for the various disorders. The authors also provide flow charts for the
      diagnostic procedures pertaining to WMSDs. The Appendix shows a sample patient
      chart illustrating the proposed procedures; it also permits the findings to be
      encoded so that they can be stored in a dedicated database. The codes for
      diagnosing WMSDs are also reported for the same epidemiological purposes.

PMID- 9148114
TI  - [Occurrence of musculoskeletal disorders in working populations not exposed to
      repetitive tasks of the upper arms].
AB  - A total of 749 workers (males: 139 aged between 15 and 35 years, and 171 aged
      over 35 years; females: 176 aged between 15 and 35 years, and 263 aged over 35
      years) performing tasks not at risk for work-related musculo-skeletal disorders
      of the upper limbs (WMSDs) underwent a clinical examination using a standardised
      method. The "anamnetics cases" were defined on the basis of pain or paraesthesia
      present for at least one week during the previous 12 months, or appearing at
      least once a month, and not subsequent to acute trauma. The anamnestic cases
      among the males amounted to 4.4% (age 15 divided by 35 years) and 12.3% (age >
      35); among the females 4.6% (age 15 divided by 35 years) and 14.2% (age > 35). Of
      the 1498 limbs examined, the prevalent pathologies reported were: suspect narrow
      chest syndrome: 0.3% among the males > 35 years, 0.6% among the females aged 15
      divided by 35 years, 1% among the females > 35 years; scapulo-humeral
      periarthritis: 0.3% among the males aged > 35 years, 0.3% among the females aged
      15 divided by 35 years, 1.3% among the females aged > 35 years; lateral
      epicondylitis: 0.3% among the males aged > 35 years, 0.2% among the females aged
      > 35 years; trapezio-metacarpal arthrosis: 0.8% among the females aged > 35
      years; wrist-hand tendinitis: 0.9% among the males aged > 35 years, 0.9% among
      the females aged 15 divided by 35 years; carpal tunnel syndrome: 2.5% among the
      females aged > 35 years. No disorders were detected outside of the age ranges
      indicated. Several workers reported more than one disorder. The number of workers
      with at least one WMSD was: males 0% in the 15 divided by 35 years age range,
      3.5% in the > 35 year age range; females 2.3% in the 15 divided by 35 year age
      range, 7.2% in the > 35 year age range; 3.9% of the total sample population. The
      prevalences were on average quite low, particularly among the older workers,
      hence the authors recommend that even minimal prevalences detected in particular
      work environments should not be underestimated.

PMID- 9148115
TI  - [Repetitive movements of the upper limbs: results of exposure evaluation and
      clinical investigation in refinishing ceramic ornaments].
AB  - An evaluation was made of the degree of exposure to risk and the frequency of
      disorders attributable to biomechanical overload of the upper limb in workers
      performing finishing operation on ceramic vases and cups in a ceramics factory.
      The risks were first evaluated against a checklist, then subsequently an
      assessment was made of the tasks found to feature the highest risks, using an
      ergonomic analysis method, which identified activities associated with a large
      number of actions per minute (> 50). The 22 female workers performing the tasks
      in question underwent a risk-targeted physical examination which included an
      electroneurographic test using surface electrodes. The clinical test detected an
      extremely high frequency of carpal tunnel syndrome cases, in addition to other
      upper limb disorders. In particular, nine female workers (41%) were found to be
      suffering from carpal tunnel syndrome, and five (22%) from other pathologies of
      the upper limbs (4 scapulo-humeral periarthritis, 1 epicondylitis). As a result
      of the findings arising out of this study, immediate preventive measures were
      adopted; moreover, it has become evident that further epidemiological studies on
      larger sample populations are needed.

PMID- 9148116
TI  - [Repetitive movements of the upper limbs: results of exposure evaluation and
      clinical investigation in the production and packaging of ice cream].
AB  - An evaluation was made of the degree of exposure to risk and the frequency of
      disorders attributable to biomechanical overload of the upper limb in workers
      employed on packaging in an ice cream factory. The risks were first evaluated
      against a checklist, then subsequently an assessment was made of the tasks found
      to feature the highest risks, using an ergonomic analysis method. The method
      identified several jobs, such as placing ice cream coupes and such like in boxes,
      as requiring a large number of actions per minute (> 30) and considerable
      muscular strength. The 59 female workers performing the packaging operations were
      given a risk-targeted physical examination. The clinical test detected an
      extremely high frequency of carpal tunnel syndrome, (7.1%) epicondylitis (5.2%)
      and scapulo-humeral periarthritis (3.5%) in the over 35 years age group, with
      respect to a control population not exposed to risk. The authors conclude that
      the repetitiveness of the actions, the use of gloves due to prolonged contact
      with frozen products and the effects of the low temperatures themselves, may have
      favoured the spread of the disorders that appeared in this population of workers.
      These findings must be further supported by more in-depth epidemiological
      studies.

PMID- 9148117
TI  - [Repetitive movements of the upper limbs: results of exposure evaluation and
      clinical investigation during the sorting and packaging of apples].
AB  - In the fruit industry, workers sorting and packing apples perform a job that is
      characterised by repetitive actions, that require them to remain in an upright
      position for prolonged periods of time and, occasionally, to manually lift loads
      of apples. The aim of the study was to detect and provide a preliminary
      quantification of any possible risks for the musculo-skeletal system, as well as
      any disorders present among the workers. A risk analysis for WMSDs was performed
      in an apple packing plant, using video recordings of the job cycles associated
      with two different tasks (semi-automatic sorting and manual packing). A clinical
      and anamnestic investigation was carried out in nine plants; a standard
      questionnaire was distributed to 180 employees, with the purpose of detecting
      disorders and diseases of the locomotor system. An initial evaluation of the
      risks for WMSDs indicated that the routine tasks performed by the female apple
      workers featured a very high frequency of actions, also in view of the fact that
      the repetitive tasks lasted for the duration of the entire work shift. In the
      situation examined, the action frequency limits were greatly exceeded; moreover,
      the recovery times were inadequate in terms both of their duration and
      distribution. Regarding clinical and anamnestic examination, an overall analysis
      of the results shows a very high prevalence of spinal and hand-arm disorders.
      Given these preliminary findings, the authors suggest that the sample population
      of fruit sorters should undergo clinical and instrumental testing to evaluate the
      condition of the spine and upper limbs, and that a specific health surveillance
      programme should be adopted across the industry.

PMID- 9148118
TI  - [Repetitive movement of the upper limbs: results of exposure evaluation and
      clinical investigation in wood sanding in Bergamo].
AB  - The authors report their findings regarding a risk assessment study and clinical
      tests carried out among a group of 121 workers whose job was to sandpaper and
      buff timber products. The results of the risk assessment indicate that the job in
      question is at significant risk for the development of WMSDs in relation to the
      principal risk factors (repetitiveness, force, posture, short recovery periods).
      The clinical tests, undertaken by medical staff, complied with the anamnestic
      models proposed by EPM. The results showed that 21 workers were above the
      anamnestic threshold, and were thus referred for specialist examinations. As a
      result of the latter, the relevant diagnoses were made. A positive correlation
      was reported between the occupational exposure level and the clinical
      abnormalities detected.

PMID- 9148120
TI  - [Repetitive movement of the upper limbs: results of exposure evaluation and
      clinical investigation in cash register operators in supermarkets].
AB  - In order to evaluate the prevalence of joint and periarticular disorders of the
      upper limbs attributable to repetitive movements (WMSDs), 100 female supermarket
      cashiers were examined. Their average age was 29.5 years (SD = 6.3), and their
      average length of service was 3.9 years (SD = 1.9). Only 26% of the women were
      anamnestically negative for WMSDs, while 74% had one or more disorders due to
      repetitive trauma of the upper limbs, although a definite diagnosis could be made
      in only 33 cases. The majority of the disorders affected the right side and the
      localisation was primarily in the shoulder and wrist. The risk factor analysis on
      the one hand confirmed that high-frequency repetitive movements of the wrist and
      hand, associated with inadequate recovery times, do play a role in determining
      the onset of upper limb and carpal tunnel syndrome. On the other hand, the study
      also revealed a definite need to review the way the work is organised, so that
      each shift at the cash register includes suitable functional recovery periods.

PMID- 9148119
TI  - [Repetitive movements of the upper limbs: results of exposure evaluation and
      clinical investigation in the manual sanding of wood in the Valdichiana region].
AB  - The aim of this study was to evaluate the level of risk exposure deriving from
      repetitive movements of the upper limbs, among a population of female workers
      manually sand papering timber products. The study also included an anamnestic and
      clinical assessment for the purpose of detecting and diagnosing WMSDs in the
      study population. The authors report a distinct prevalence of such disorders
      among the female workers exposed to a high level of risk, also in view of the
      total absence of recovery periods.

PMID- 9148122
TI  - [Outbreak of carpal tunnel syndrome of the upper limbs in automobile seat
      assemblers: results of exposure evaluation and clinical investigation].
AB  - A group of 59 female workers in the sewing and upholstery departments of a
      factory manufacturing automobile seats underwent clinical and instrumental tests
      following reports of several cases of suspected carpal tunnel syndrome. A risk
      evaluation analysis for disorders attributable to repeated trauma of the upper
      limbs (WMSDs) was simultaneously carried out using the protocol recommended by
      the EPM Research Unit in Milan. Evidence was found of a high frequency of
      elementary actions associated with considerable muscular involvement along with
      inadequate recovery periods. The clinical investigation revealed an unusually
      high percentage of carpal tunnel syndromes, often associated with Guyon channel
      syndrome. This disorder affects males and females equally, is often bilateral,
      and is not associated with known non-occupational factors. The widespread
      outbreak of work-related musculo-skeletal disorders reported in the departments
      in question may have arisen from a combination of significant risk factors
      relating to the types of activities performed, and the long service of the
      workers. It is reasonable to assume that failure to adopt technical preventive
      and organisational measures may have stemmed primarily from a poor evaluation of
      the relevant occupational risks, and from many years of substandard health
      surveillance practices.

PMID- 9148121
TI  - [Repetitive movement of the upper limbs: results of exposure evaluation and
      clinical investigation during jar packaging of preserved vegetables].
AB  - In order to assess the prevalence of work-related musculo-skeletal disorders of
      the upper limbs, a total population of 29 female workers in an industrial
      vegetable preserving plant were examined. The average age of the workers was 41.3
      years (SD = 9.2), and their average length of service was 16.7 years (SD = 7.2).
      Only 20% of the workers were anamnestically negative, whilst 80% had one or more
      disorders attributable to repetitive trauma of the upper limbs. The disorders
      showed no prevalence for the right side, a finding in line with the risk analysis
      which indicated that both limbs were equally used. The results of the risk
      analysis and clinical assessment confirm that high-frequency actions, combined
      with improper posture and a shortage of suitable recovery times, play a causal
      role in determining the onset of the disorders studied.

PMID- 9148123
TI  - [Repetitive movement of the upper limbs: results of a current exposure evaluation
      and a clinical investigation in workers employed in the preparation of pork meat
      in the province of Modena].
AB  - Exposure assessment tests were undertaken to measure the biomechanical overload
      factors affecting the upper limbs. The tests were carried out on a group of 86
      workers employed on the cutting, boning and trimming line of a pork meat
      processing plant. Anamnestic screening and clinical tests targeted at correlated
      disorders were also performed and were followed by instrumental tests. The
      results are reported with respect to frequency of repetitive technical actions,
      degree of muscular involvement, postural risk, several complementary factors and
      distribution of recovery periods. The clinical investigation showed a high
      prevalence of carpal tunnel syndrome, tendon disorders of the hand and
      epicondylosis of the elbow, in addition to other disorders. The report confirms
      the presence of additional risks for the workers, both in the past and under
      present circumstances, and suitable preventive measures are formulated.

PMID- 9148124
TI  - [Evaluation of the exposure to biomechanical overload of the upper limbs and
      clinical investigation in a female population employed in the manual loading of
      production lines in 2 ceramics factories].
AB  - The aim of this study was to assess the presence of an increased risk of
      biomechanical overload of the upper limbs in the ceramics industry, among workers
      manually loading production lines. The study focused on two factories: in the
      first, most of the work was performed manually, whilst in the second the
      manufacturing process had been almost entirely automated. A total of 46 female
      workers were examined in both factories, to check for the presence of any
      disorders of the shoulder, elbow and wrist, as well as for any signs of carpal
      tunnel medial nerve pain. Approximately two thirds of the workers had positive
      results of the examinations and went on to undergo 2nd level testing (physiatric
      examination, muscle tendon US, electromyography) to confirm the diagnosis. In
      both factories, an increased risk was detected in terms of intensity of exertion,
      frequency of actions and inadequate recovery times. The posture and movements
      analysis showed that each of the segments of the upper limbs studied were
      involved. In both factories, at least 3 out of every 4 workers tested positive
      for a disorder of at least one segment. Diagnoses were almost invariably
      confirmed by the 2nd level tests. The progressive automation of the ceramics
      industry over recent years does not seem therefore to have reduced the risk of
      biomechanical overload disorders in the upper limbs, at least in relation to
      those jobs which still feature manual tasks. In view of the social costs
      associated with such disorders, it would appear mandatory to pursue the
      investigation further, particularly focusing on those jobs (e.g. polishing,
      cutting, special shapes, etc.) which can be expected to feature manual tasks.

PMID- 9148125
TI  - [Carpal tunnel syndrome in workers engaged in the assembly of manufactured
      products in various industries in the province of Brescia].
AB  - Tests were carried out on five manual assembly departments in a variety of
      different factories, in order to assess the risks associated with the onset of
      Carpal Tunnel Syndrome and to describe the prevalence of this disorder among
      exposed workers. The application of the risk analysis method proposed by the EPM
      Research Unit in Milan (Italy) demonstrated the presence of numerous jobs
      featuring both a high frequency of actions per minute and a total lack of
      recovery times, in addition to a variety of incongrous upper limb postures. The
      clinical and instrumental investigation diagnosed 76 cases of Carpal Tunnel
      Syndrome among the 170 exposed workers. 62% of the cases was bilateral and 24%
      was associated with Guyon Channel Syndrome. In two of the five departments
      reviewed, the carpal tunnel disorders detected were endemic, and featured
      unusually high prevalence. The situation had been seriously underestimated by the
      company technical and medical staff, resulting in a failure to call for the
      urgent adoption of individual protection and collective prevention measures. The
      authors recommend that an extensive and adequate occupational risk assessment
      analysis be performed: the local occupational health services could play a
      critical role in identifying the highest risk industries and the diseases
      diagnosed in a hospital environment.

PMID- 9148126
TI  - [Investigation in a slaughter house and processing of pork meat. Repetitive task
      work and osteo-articular and musculotendinous pathology of the upper limbs].
AB  - The investigation concerned 47 workers (43 males and 4 females), whose average
      age was 41.5 years and average length of service 12 years. The aim of the study
      was to quantify the presence in an abattoir and meat processing plant of risk
      factors represented by repetitive movements requiring the use of force, and to
      describe the work-related musculo-skeletal disorders (WMSDs) of the upper limbs
      found in a group of workers exposed to such risk factors. The work was found to
      feature high speeds and very particular operations which, for most of the
      workers, required highly repetitive actions often associated with the use of
      force. Almost all the tasks had duration cycles of less than 30 seconds and a
      medium-high rate of actions/minute (from 20 to 60), with peak rates reached in
      the boning operations; the postural involvement was also considerable,
      particularly for the right wrist. The amount of force employed-calculated as a
      percentage of the Maximum Voluntary Contraction-averaged 50%. With very few
      exceptions, there were no significant pauses during the cycle. The group
      displayed a high prevalence of pain and paraesthesia and joint disorders,
      particularly in the over 35 age groups; statistically significant differences
      emerged with respect to the data from a matched population sample given the same
      anamnestic and clinical protocol. The group also exhibited significantly
      different Carpal Tunnel Syndromes with respect to the control population: 7 right
      hand CTSs and five left-hand. CTS affected two out of every three women aged over
      35 and 3 out of every 23 men over 35. The authors discuss the results in the
      light of previous studies and of the definition of CTS. The study concludes that
      investigating and preventing WMSDs in the meat processing industry is a
      justified, albeit very difficult, task whilst the protection afforded by current
      legislation appears to be most inadequate.

PMID- 9148127
TI  - [The application of the concise exposure index to repetitive movement tasks of
      the upper limbs in various production settings: preliminary experience and
      validation].
AB  - A summary of eight investigations is presented, which were carried out using
      standardised methods, for the purpose of quantifying exposure to tasks involving
      repetitive movements of the upper limbs, as well as quantifying the prevalence of
      Work Related Musculo Skeletal Disorders of the upper limbs in groups of exposed
      workers. A total of 462 exposed workers were examined, and the study also took
      into account the data pertaining to a matched control group comprising 749
      workers not exposed to any specific occupational risk. Regarding the
      quantification of exposure to increased risk, use was made of a Concise Index
      (OCRA), proposed by the Authors in a previous publication. The data resulting
      from the eight investigations were used for the study of measurements and models
      of association among the exposure variables (mainly represented by the OCRA
      index), as well as the effect variables represented by the prevalence of the
      various WMSDs of the upper limbs taken both individually and jointly. Significant
      associations were reported between the OCRA index and an effect indicator
      represented by the prevalence of all the WSMDs of the upper limbs, calculated on
      the number of upper limbs at risk. When a logarithmic conversion of the relative
      exposure (OCRA) and injury indices was carried out, a simple linear regression
      model resulted which seems to provide a satisfactory predictive performance of
      the risk of WMSDs of the upper limbs, based on the exposure index. The study
      confirmed the efficacy of various other models designed to predict effects based
      on multiple linear regression functions, in which the independent variables are
      represented by both the OCRA exposure index and by parameters relative to the
      breakdown by sex and age of the groups of exposed workers.

PMID- 9148128
TI  - [Criteria for the health surveillance of WMSDs in exposed working populations].
AB  - In the light of the experiences and guidelines developed by other countries and
      of Italian legislative and operational conditions, the authors outline a strategy
      for a health surveillance programme for work-related musculo-skeletal disorders
      of the upper limbs. In particular, the paper defines the various aims of the
      health surveillance programme and identifies significant relevant criteria for
      its implementation (i.e. existence of risks or effects). A screening schedule is
      presented based on successive investigations (1st and 2nd level surveillance);
      the authors discuss the principal methods used for processing the results of the
      health surveillance programme, in collective (i.e. statistical comparisons;
      planning of periodical investigations) and individual terms (job fitness
      judgements; reporting of suspected occupational diseases.

PMID- 9148129
TI  - [Guidelines for redesigning jobs with repetitive tasks].
AB  - Preventive measures aimed at minimising the occurrence of work-related musculo
      skeletal disorders of the upper limbs (WMSDs) associated with repetitive tasks
      can be divided into 3 categories: structural, organisational and educational.
      Whenever specific risk and injury assessments have shown the need for preventive
      action, this is most often implemented within the framework of a range of
      assorted measures. In particular, structural measures pertain to optimising the
      layout of the work area and furnishings, and the "ergonomic" properties of work
      tools and equipment. Such measures serve to alleviate the problems caused by the
      use of excessive force and improper postures. The authors refer to the principles
      guiding such structural measures, in the light of the extensive literature that
      has been published on the subject. Organisational (or re-organisational) measures
      essentially relate to job design (i.e. distribution of tasks, speeds and pauses).
      They serve to alleviate problems connected with highly repetitive and frequent
      actions, excessively lengthy tasks and inadequate recovery periods. Very few
      relevant findings are available: the authors therefore illustrate in some detail
      a practical trial conducted in a major engineering firm. The objective was to
      lower to acceptable limits the frequency of certain repetitive tasks performed by
      workers using their upper limbs. The trial made it possible to identify a
      suitable plan and schedule of measures taking into due consideration the impact
      of the plan on production levels (and costs). The fundamental principles guiding
      the adoption of specific educational and training programmes for the workers and
      their supervisors are presented and discussed.

PMID- 9148130
TI  - [Criteria for the reintegration to their jobs of workers with musculoskeletal
      pathologies of the upper limbs based on preliminary practical experiences].
AB  - The report presents a preliminary study on the return to the workforce of
      employees with WMSDs of the upper limbs, and their reallocation to jobs with "low
      exposure". The study, which is still underway, involves a large engineering firm
      and includes some 100 workers affected by WMSDs. The trial envisages: providing a
      definition of the criteria for characterising "accommodating" jobs (i.e.
      frequency of action < or = 20 actions per minute; virtual absence of other risk
      factors such as force, posture, inadequate pauses, etc.); concretely identifying
      jobs meeting such criteria (or jobs which, with minimal modifications, could be
      made suitable); classifying WMSDs workers, according to the type and severity of
      the disorder; matching WMSDs workers with the jobs best suited to them; specific
      training for the workers and their supervisors; carrying out a follow-up of the
      return of WMSDs workers to the workforce in organisational terms (i.e. need for
      further modifications to equipment or procedures) and clinical terms (i.e.
      symptom patterns, acceptability of the condition). The preliminary results, 6-12
      months after the start of the trial, are extremely encouraging, and show that
      when workers return to the workforce in jobs that fully meet defined criteria, a
      significant prevalence of "improvements" are reported among the involved workers.
      The investigation will need to be extended, but already it shows quite
      convincingly that it is possible for workers with what can be described as a
      "reduced working capacity" to remain "productive" (albeit in jobs featuring a
      lower exposure potential than the acceptable threshold for "healthy" workers).

PMID- 9148131
TI  - [Unlisted osteoarticular pathologies. The National Insurance Institute for
      Occupational Diseases approach].
AB  - In the case of unlisted microtraumas, the patient must first be evaluated in
      terms of his or her risk exposure, followed by an exact determination of the
      relationship of causal dependency, and lastly an accurate diagnosis must be made.
      Since the disorder is not listed as an automatically compensated disease, the
      burden of proof lies with the insured. Regarding microtraumas, in particular, the
      causes must be studied with reference to: chronological criteria, qualitative and
      quantitative efficiency factors, topographic criteria, modal criteria, continuity
      of event seriation, evidence of unrelated pathogens. The principle of adequate
      causality appears to be the only one offering a sufficient guarantee of
      scientific exactness in determining the relationship of causal dependency. At
      present, Circ. 35/92 of INAIL regulations states that the work-relatedness of
      microtraumas may be admitted when the worker's personal history (anamnesis)
      points to the existence of an occupational risk whose nature, duration and
      intensity can reasonably be considered as to exert an equal or higher influence
      than that exerted by non-occupational aetiological factors. The statistical and
      epidemiological data must demonstrate a significantly higher incidence of the
      pathology among a given category of workers. Only cases featuring the
      aforementioned characteristics, are currently legally entitled to the relevant
      insurance services.

PMID- 9148132
TI  - [Insurance coverage in repetitive strain injury of the upper limbs as provided by
      the National Insurance Institute for Occupational Diseases].
AB  - A brief outline is given of the current status of the insurance "coverage"
      provided by INAIL for WMSDs. In breach of a specific European Union
      recommendation, in Italy various WMSDs can be recognised as occupational only
      based upon sentence No 179/88 of the Constitutional Court, since such disorders
      are not included in the list attached to DPR law 336/94. At present, during the
      period 1990-95, INAIL awarded indemnities in only a handful of cases. Details are
      provided concerning the evidence that must be submitted in the specific case of
      claims pertaining to suspected occupational diseases. The authors discuss the
      problems associated with quantifying injuries for the purposes of claiming
      indemnities for work-related musculo-skeletal disorders.

PMID- 9148133
TI  - Case definitions for infectious conditions under public health surveillance.
      Centers for Disease Control and Prevention.
AB  - State and local public health officials rely on health-care providers,
      laboratories, and other public health personnel to report the occurrence of
      notifiable diseases to state and local health departments. Without such data,
      trends cannot be accurately monitored, unusual occurrences of diseases might not
      be detected, and the effectiveness of intervention activities cannot be easily
      evaluated. In the United States, requirements for reporting diseases are mandated
      by state laws or regulations, and the list of reportable diseases in each state
      differs. In October 1990, in collaboration with the Council of State and
      Territorial Epidemiologists, CDC published Case Definitions for Public Health
      Surveillance (MMWR 1990;39[No. RR-13]), which, for the first time, provided
      uniform criteria for reporting cases. This report provides updated uniform
      criteria for state health department personnel to use when reporting the
      nationally notifiable infectious diseases listed in Part 1 of this report. A
      revision date is listed for each case definition that has been revised. Newly
      generated case definitions that have not been published previously are designated
      as "adopted" on the specified date. Case definitions for some infectious
      conditions not designated as nationally notifiable are included in Part 2 of this
      report. Some of these conditions may have been nationally notifiable or may
      become so; definitions are included here to facilitate interpretation of data for
      these diseases. These conditions may be reportable in some states.

PMID- 9148135
TI  - Alcohol and other Drug-Related Birth Defects Awareness Week--May 11-17, 1997.

PMID- 9148134
TI  - Prevention and control of influenza: recommendations of the Advisory Committee on
      Immunization Practices (ACIP).
AB  - These recommendations update information concerning the vaccine and antiviral
      agents available for controlling influenza during the 1997-98 influenza season
      (superseding MMWR 1996;45[No. RR-5]:1-24). The principal changes include
      information about a) the influenza virus strains included in the trivalent
      vaccine for 1997-98, b) the vaccination of pregnant and breastfeeding women, and
      c) side effects and adverse reactions.

PMID- 9148136
TI  - Alcohol consumption among pregnant and childbearing-aged women--United States,
      1991 and 1995.
AB  - Moderate to heavy alcohol use by women during pregnancy has been associated with
      many severe adverse effects in their children, including fetal alcohol syndrome
      (FAS)--with facial dysmorphology, growth retardation, and central nervous system
      deficits--and other neurodevelopmental effects. Early prenatal alcohol exposure
      can occur unintentionally (i.e., before a woman knows she is pregnant); in
      addition, women who drink at high levels before pregnancy are at increased risk
      for drinking during pregnancy. Ongoing surveillance for alcohol consumption among
      pregnant and childbearing-aged women is important for monitoring the impact of
      efforts to prevent this risk behavior. This report analyzes and compares data
      from the 1995 Behavioral Risk Factor Surveillance System (BRFSS) and previously
      reported 1991 BRFSS data for women aged 18-44 years, and presents the prevalence
      of alcohol consumption among pregnant women and overall and state-specific
      prevalence rates among women of childbearing age. The findings indicate a
      substantial increase in alcohol use among pregnant women from 1991 to 1995.

PMID- 9148137
TI  - Rubella and congenital rubella syndrome--United States, 1994-1997.
AB  - Indigenous rubella and congenital rubella syndrome (CRS) have been targeted for
      elimination in the United States by the year 2000. Progress toward reaching this
      goal is monitored through the National Notifiable Diseases Surveillance System
      and the National Congenital Rubella Syndrome Registry. From 1969 through 1989,
      the numbers of annual reported cases decreased 99.6% for rubella and 97.4% for
      CRS. Following a slight resurgence during 1990-1991, the number of reported
      rubella cases reached record lows during 1992-1996 (annual average: 183 reported
      cases). This report summarizes the characteristics of rubella and CRS cases and
      outbreaks reported in the United States from 1994 through 1996 and provisional
      data as of April 18, 1997. The findings indicate sustained low incidence of
      rubella and CRS since 1992 and possible interruption of transmission of rubella
      virus in late 1996.

PMID- 9148138
TI  - Outbreaks of pseudo-infection with Cyclospora and Cryptosporidium--Florida and
      New York City, 1995.
AB  - Efforts to expand the scope of surveillance and diagnostic testing for emerging
      infectious diseases also may increase the potential for identifying pseudo
      outbreaks (i.e., increases in incidence that may result from enhanced
      surveillance) and outbreaks of pseudo-infection (i.e., clusters of false
      positives for infection). This report describes the investigations of outbreaks
      of pseudo-infection with Cyclospora in Florida and Cryptosporidium in New York
      City in 1995 after health departments in those jurisdictions had initiated
      surveillance for these emerging organisms. These investigations emphasize 1) the
      need for laboratory training in the identification of emerging pathogens and 2)
      the importance of confirmation by reference laboratories as an early step in the
      investigation of any apparent outbreak caused by an emerging pathogen.

PMID- 9148139
TI  - Adult blood lead epidemiology and surveillance--United States, Fourth Quarter,
      1996.
AB  - CDC's National Institute for Occupational Safety and Health Adult Blood Lead
      Epidemiology and Surveillance program (ABLES) monitors laboratory-reported
      elevated blood lead levels (BLLs) among adults in 25 states. This report presents
      ABLES data through the fourth quarter of 1996, compares these data with that from
      the same period in 1995, and describes cases of severe lead poisoning in adults
      in New York during 1996.

PMID- 9148140
TI  - National Melanoma/Skin Cancer Detection and Prevention Month--May 1997.

PMID- 9148141
TI  - Media dissemination of and public response to the Ultraviolet Index--United
      States, 1994-1995.
AB  - Exposure to the ultraviolet component of sunlight may be associated with an
      increased risk for some skin cancers. The Ultraviolet Index (UVI) links a rating
      by the National Weather Service (NWS) of solar ultraviolet intensity (on a scale
      of 0 [minimal] to 10+ [very high]) to recommendations for appropriate sun
      protection behaviors. During the summers of 1994 and 1995, the NWS, in
      collaboration with the Environmental Protection Agency (EPA), the American
      Academy of Dermatology, the National Association of Physicians for the
      Environment, and CDC, disseminated UVI forecasts to selected major television
      stations and newspapers in the United States. In 1995, the Boston University
      School of Medicine conducted three surveys to evaluate how widely the UVI was
      televised, printed in newspapers, and used by adults (aged > or = 18 years) to
      modify their behaviors to reduce exposure to ultraviolet light. This report
      summarizes the findings of the elevation, which indicate generally high rates of
      television broadcast and public awareness of the UVI.

PMID- 9148142
TI  - Contraceptive practices before and after an intervention promoting condom use to
      prevent HIV infection and other sexually transmitted diseases among women-
      selected U.S. sites, 1993-1995.
AB  - Because heterosexual contact is the most common mode of human immunodeficiency
      virus (HIV) transmission among women, development of effective strategies to
      reduce sexually transmitted HIV infection is critical. In addition, because most
      women at risk for HIV infection are reproductive aged (14-44 years), effective
      use of contraceptives is important to prevent unintended pregnancies. Latex
      condoms used by males, when used consistently and correctly, are highly effective
      at reducing the risk for HIV infection and other sexually transmitted diseases
      (STDs); however, hormonal contraceptive methods or surgical sterilization are
      more effective for preventing pregnancy. One possible effect of encouraging women
      to use condoms for HIV/STD prevention with their male partners is that women may
      discontinue use of hormonal contraceptive methods. To assess whether encouraging
      women to use condoms for HIV/STD prevention affects their contraceptive
      practices, CDC analyzed longitudinal data on contraceptive methods and condom use
      for HIV/STD prevention that were collected as part of a randomized trial
      evaluating HIV-counseling methods during August 1993-June 1995. This report
      summarizes the findings of the analysis, which indicate that, among reproductive
      aged women who were encouraged to use condoms for HIV/STD prevention, consistent
      condom use for HIV/STD prevention increased among women using each contraceptive
      method studied. In addition, most women using hormonal contraceptive methods
      continued to use them after the intervention, and the overall proportion of women
      protected against pregnancy increased.

PMID- 9148143
TI  - Program to prevent perinatal hepatitis B virus transmission in a health
      maintenance organization--Northern California, 1990-1995.
AB  - Each year, an estimated 20,000 infants are born to hepatitis B surface antigen
      (HBsAg)-positive women in the United States. These infants are at high risk for
      perinatal hepatitis B virus (HBV) infection, chronic HBV infection, and
      associated complications of chronic liver disease, including cirrhosis and
      hepatocellular carcinoma. All vaccine advisory groups recommend that all pregnant
      women be routinely tested for HBsAg during an early prenatal visit during each
      pregnancy to determine whether their newborns will require immunoprophylaxis for
      the prevention of perinatal HBV infection. Administration of appropriate
      immunoprophylaxis is approximately 90% effective in preventing HBV infection
      among children born to HBsAg-positive mothers. In 1995, the Kaiser Permanente
      Medical Care Program of Northern California (KP)--a health-maintenance
      organization (HMO) providing care to 2.5 million members and delivering 30,000
      infants annually--implemented HBsAg screening of all pregnant women. After
      initiating the program, KP estimated that at least 25% of the infants born to
      HBsAg-positive women were not receiving appropriate post-exposure prophylaxis. In
      response, KP implemented a tracking and follow-up program in 1988. This report
      describes an assessment of the impact of this program, which indicates that a
      centralized case-management and tracking system can substantially improve levels
      of post-exposure prophylaxis.

PMID- 9148144
TI  - Availability of diphtheria antitoxin through an investigational new drug
      protocol.

PMID- 9148145
TI  - Effect of atenolol on mortality and cardiovascular morbidity after noncardiac
      surgery.

PMID- 9148146
TI  - Effect of atenolol on mortality and cardiovascular morbidity after noncardiac
      surgery.

PMID- 9148147
TI  - Effect of atenolol on mortality and cardiovascular morbidity after noncardiac
      surgery.

PMID- 9148148
TI  - Effect of atenolol on mortality and cardiovascular morbidity after noncardiac
      surgery.

PMID- 9148149
TI  - Minimally invasive coronary-artery bypass surgery without extracorporeal
      circulation.

PMID- 9148150
TI  - Preliminary experience with minimally invasive coronary-artery bypass surgery
      combined with coronary angioplasty.

PMID- 9148151
TI  - Adjunctive drug therapy for acute myocardial infarction.

PMID- 9148152
TI  - Adjunctive drug therapy for acute myocardial infarction.

PMID- 9148153
TI  - The DCC protein and colon cancer.

PMID- 9148154
TI  - The DCC protein and colon cancer.

PMID- 9148155
TI  - The DCC protein and colon cancer.

PMID- 9148156
TI  - The Canale-Smith syndrome.

PMID- 9148157
TI  - Clinical problem-solving: when too much is too little.

PMID- 9148158
TI  - Clinical problem solving: when too much is too little.

PMID- 9148159
TI  - Clinical problem solving: when too much is too little.

PMID- 9148161
TI  - [Iatrogenic collapse; can this be prevented?].
AB  - In four patients, two men aged 65 and 35 years, and two women aged 87 and 83
      years, who presented with collapse, administration of Q-T time prolonging drugs
      (sotalol, erythromycin, disopyramide) appeared to be the cause. These patients
      had so-called 'concealed long Q-T syndrome'. The proarrhythmogenic properties of
      antiarrhythmic and other drugs and of several clinical conditions such as cardiac
      diseases should be kept in mind when treating patients with antiarrhythmic
      substances.

PMID- 9148160
TI  - Decision analysis--effects of prophylactic mastectomy and oophorectomy on life
      expectancy among women with BRCA1 or BRCA2 mutations.
AB  - BACKGROUND: Women with BRCA1 or BRCA2 mutations have an increased risk of breast
      cancer and ovarian cancer. Prophylactic mastectomy and oophorectomy are often
      considered as ways of reducing these risks, but the effect of the procedures on
      life expectancy has not been established. METHODS: In a decision analysis, we
      compared prophylactic mastectomy and prophylactic oophorectomy with no
      prophylactic surgery among women who carry mutations in the BRCA1 or BRCA2 gene.
      We used available data about the incidence of cancer, the prognosis for women
      with cancer, and the efficacy of prophylactic mastectomy and oophorectomy in
      preventing breast and ovarian cancer to estimate the effects of these
      interventions on life expectancy among women with different levels of risk of
      cancer. RESULTS: We calculated that, on average, 30-year-old women who carry
      BRCA1 or BRCA2 mutations gain from 2.9 to 5.3 years of life expectancy from
      prophylactic mastectomy and from 0.3 to 1.7 years of life expectancy from
      prophylactic oophorectomy, depending on their cumulative risk of cancer. Gains in
      life expectancy decline with age at the time of prophylactic surgery and are
      minimal for 60-year-old women. Among 30-year-old women, oophorectomy may be
      delayed 10 years with little loss of life expectancy. CONCLUSIONS: On the basis
      of a range of estimates of the incidence of cancer, prognosis, and efficacy of
      prophylactic surgery, our model suggests that prophylactic mastectomy provides
      substantial gains in life expectancy and prophylactic oophorectomy more limited
      gains for young women with BRCA1 or BRCA2 mutations.

PMID- 9148162
TI  - [The relationship between marital status and health].
AB  - In the Netherlands there are considerable health differences by marital status;
      differences are found in subjective and objective health measures, in mental and
      physical health, and in morbidity and mortality. In general divorced people have
      the most and married people the least health problems. Married people have less
      health problems than unmarried people living with a partner. Differences in
      mortality by marital status are smaller among women than among men. There are two
      explanatory theories: the social causation theory (marital status influences
      health) and the selection theory (health influences marital status). Both
      theories play a role in the explanation of the health differences. The effect of
      marital status on health among men is mainly mediated by psychosocial factors,
      whereas material circumstances are the principal intermediary factor among women.
      Health intervention among unmarried men should be aimed at intensifying social
      support from the environment, among divorced women it should be aimed at
      improving material conditions.

PMID- 9148163
TI  - [Sex differences in perceived health].
AB  - Findings from health surveys show that women report more physical complaints than
      men. These sex differences have been attributed to physical, psychological and
      social factors. In a large-scale morbidity registration project in general
      practice in Nijmegen (the Netherlands) women reported more 'medically unexplained
      symptoms' to their GP, but especially had more sex-specific (gynaecological)
      problems and consultations for preventive purposes. An empirical study among 173
      healthy GP patients showed that the general tendency to report physical symptoms
      (somatization) is higher in women than in men. The higher symptom score in women
      can be explained with the symptom perception model: women have more negative
      affectivity, more selective attention for their bodies and less distraction from
      the surroundings, which enhances somatization. The differences in perceived
      health are the result of the (sex-specific) way in which men and women perceive
      and interpret their symptoms and the (sex-specific) way in which they act upon
      them by consulting their GP.

PMID- 9148164
TI  - [More of the Surinam and Antilles drug addicts involved in the GG&GD (Community
      Medical and Health Service) methadone program in Amsterdam should be referred to
      the family physician for their methadone maintenance].
AB  - OBJECTIVE: To study the possibility of referring Surinam and Netherlands
      Antillean drug users from a 'low-threshold' municipal methadone programme to
      general practice for methadone maintenance treatment. (Methadone maintenance
      treatment for drug users leads to a more regulated life and makes it possible to
      implement measures to ameliorate their living conditions.) Fewer Surinam and
      Netherlands Antillean drug users are referred to general practice than native
      Dutch drug users. DESIGN: Descriptive. SETTING: Municipal Health Service,
      Department of Mental Health, Unit on Drugs, Amsterdam, the Netherlands. METHOD:
      141 Surinam and Netherlands Antillean drug users participating in the 'low
      threshold' methadone programme were examined on the following items: psychiatric
      status, drug and alcohol abuse, judicial problems, relationships, personal care,
      insurance and housing. With these items the level of regulated drug use was
      assessed and the possible reference to general practice evaluated. RESULTS: 21%
      of the drugs user group was found to be well regulated. They could have been
      referred to general practice immediately. Another 18% were also well regulated
      but they received methadone on a daily basis at the moment of investigation; when
      they would have proven to manage methadone prescription on a weekly basis, they
      could also be referred to general practice. 61% could not be referred because
      they were addicted to benzodiazepines (22%) or alcohol (33%), lived in unsuitable
      housing (45%), had judicial problems (53%), psychiatric problems (30%) or no
      insurance (15%), or were very problematic drug users receiving Palfium
      (dextromoramide) through the 'low-threshold' municipal methadone programme (15%).
      CONCLUSION: Of Surinam and Netherlands Antillean drug users from a municipal
      methadone programme, approximately 20% could have been directly referred to
      general practice for their methadone maintenance treatment and 20% at a later
      stage, and 60% could not.

PMID- 9148165
TI  - [Anticipated effects of experimental heroin prescription on the method of
      administration and the use of other drugs].
AB  - OBJECTIVE: Pending a Dutch heroin prescription trial (intended to regulate drug
      abuse), preliminary research was conducted into client factors that may influence
      the course and outcome, notably into administration patterns and changes in
      concomitant use of other drugs. DESIGN: Interview. SETTING: Methadone programme
      Baan in Rotterdam, the Netherlands. METHOD: In a Rotterdam methadone programme,
      60 clients were identified matching the target group of a heroin prescription
      trial; 42 respondents were interviewed. Using a semistructured questionnaire,
      data were collected on characteristics of drug use in the preceding month.
      RESULTS: In addition to their methadone supply, the majority (90%) of the
      respondents used both heroin and cocaine. Heroin and cocaine were smoked as well
      as injected by 22% and 31% respectively. In the choice of a route of
      administration individually experienced effects played a major part, which
      suggests that participation in a prescription trial will not lead to shifts in
      employed routes of administration. Cocaine was often found to have a central
      position in polydrug use, while the function of heroin was mostly that of a
      modulator. This suggests that no direct effect on the use of cocaine can be
      expected from the prescription of heroin. On the contrary, the relationship
      between the available amount of money and the cocaine used was such that,
      considering that participants in a prescription trial may be left with more
      money, a prescription trial might lead to an increased use of cocaine.
      CONCLUSION: The prescription of heroin does not seem to have a direct effect on
      the use of cocaine. Indirectly the use of cocaine might increase.

PMID- 9148166
TI  - [Ehlers-Danlos syndrome IV: phenotype variation].
AB  - In three female patients, 20, 4 and 29 years of age, Ehlers-Danlos syndrome (EDS)
      IV was diagnosed on the basis of a deficiency of collagen III with among other
      things a hyperextensible skin and joints and easy bruising. Severity of symptoms
      varies considerably per patient. EDS comprises 10 types. Type IV is the most
      severe type because of its often lethal complications like arterial rupture.
      Deficiency of collagen III is also seen in EDS patients without the classical
      severe EDS IV phenotype. It is suggested to restrict collagen III analysis to
      patients who are suspected of having classical EDS IV.

PMID- 9148167
TI  - [Idiopathic CD4(+)-T-lymphocytopenia].
AB  - Three patients, two men aged 27 and 33 years and one woman aged 31 years,
      developed several opportunistic infections without presence of HIV infection.
      Patient A died after suffering Candida stomatitis, extrapulmonary Mycobacterium
      avium infection, cytomegalovirus infection and Aspergillus pneumonia; patient B
      recovered from a disseminated M. kansasii infection; patient C suffered from
      verrucae planae. These patients had CD4(+)-T lymphocytopenia, a shortage of
      helper T cells. Idiopathic CD4(+)-T lymphocytopenia is a heterogeneous
      pathological condition with normal serum immunoglobulin concentrations. Treatment
      consists of combating and preventing infections.

PMID- 9148169
TI  - [Aspects of pica in adult psychiatric patients].

PMID- 9148168
TI  - [Hypothermia during use of pipamperone].
AB  - Two women aged 84 and 86 years developed hypothermia after use of pipamperone. In
      one of the patients repeated administration of pipamperone again induced a
      decrease of body temperature. Although other clinical and environmental factors
      may have contributed to the development of hypothermia, a causal relationship
      between the use of pipamperone and the fall in body temperature appears likely
      considering the close temporal relationship. Hypothermia has been documented as a
      side effect of neuroleptics, especially phenothiazines, but it has not been
      reported in relation to pipamperone. Hypothermia is a potentially lethal
      condition; the cases described confirm the necessity of being careful with use of
      neuroleptics in elderly people.

PMID- 9148170
TI  - [Certain clinical and epidemiological problems of reversible ischemic
      neurological deficit].
AB  - The studied material comprised 280 patients hospitalized for the first time for
      reversible ischaemic neurological deficit. The clinical condition of the
      patients, the incidence of hypertension (48.3%), ischaemic heart disease (36.4%)
      and diabetes (4.3%) was assessed and the indices were calculated of first
      admissions to hospital and the individual groups of diseases. The annual
      incidence of the RIND was 22.7/100 thousand, 3.6/100 thousand for TIA in the
      population of Warsaw City District.

PMID- 9148171
TI  - [Analysis of the clinical state and disease course in patients with acute stroke
      and reversed blood flow in the ophthalmic artery].
AB  - Fifty-four patients with acute stroke and reversed flow in the ophthalmic artery
      were analysed. Fifty-three had ischaemic stroke and one had subarachnoid
      haemorrhage. Reversed blood flow in the ophthalmic artery in stroke was more
      frequent in men (76%) and the mean age of men was significantly lower that of
      women--59.5 and 64.8 years respectively. In the acute phase of stroke (30 days)
      no patient died, and most (61.1%) improvement.

PMID- 9148172
TI  - [Clinical trial of the first Polish levodopa preparation in the treatment of
      Parkinsonian patients].
AB  - In three neurological centres the therapeutic effects and adverse effects were
      compared of two levodopa preparations combined with carbidopa (25/250): 1. A
      foreign drug widely prescribed in Poland, and 2. Its Polish analogue produced by
      Polfa Stargard Works. The drugs were given to 30 patients (in two matched groups)
      with Parkinson disease or syndrome during 6 weeks. The trial was completed by 28
      patients (one patient dropped out from each group for reasons not directly
      connected with the treatment). The therapeutic results were assessed on the basis
      of effects obtained in the NUDS and NSP scales and by measuring of the "on" phase
      at the beginning and at the end of the trial. In every case the global assessment
      of patient's condition by the patient and by the doctor was considered. The
      analysis of the results showed no significant statistically differences between
      both drugs respect to antiparkinsonian action and incidence of adverse effects.

PMID- 9148173
TI  - [Morphometric assessment of lesions in the dopaminergic nigrostriatal system in
      Parkinson disease].
AB  - The qualitative changes in substantia nigra were analysed in the material of 25
      cases of Parkinson's disease. A morphometric quantitative study of depletion of
      pigmented dopaminergic cells of substantia nigra was performed in six long-term
      cases of the disease. In addition, the number of melanin nodules was assessed as
      a marker of cell disintegration. The results obtained were compared with the
      morphometric evaluation of neuronal depletion in the mesocorticolimbic system
      (ventral tegmental area-VTA). The qualitative study indicated that melanin
      depletion in dopaminergic cells of substantia nigra in Parkinson's disease is
      diffuse and it is located mainly in the lateral alfa layer. Neuronal depletion
      with concomitant numerous extracellular neuromelanin nodules and granules was
      observed. A slight astrocytic gliosis free of macrophages accompanied cellular
      changes. The qualitative changes in substantia nigra are similar to those
      observed in VTA. The morphometric evaluation revealed that depletion of
      dopaminergic neurons in substantia nigra in Parkinson's disease is 73%, on
      average, while in VTA it remains under 5%. Hence, depletion in substantia nigra
      is much more intense. The analysis of the relationship between the number of
      neurons in substantia nigra and the age of subjects in the control group
      indicated that the number of neurons decreased proportionally to the age. In the
      group under study no significant relationship between neurons depletion and
      duration of disease or patients age was found. In the studied group of patients
      with Parkinson's disease, the number of melanin nodules in substantia nigra was
      significantly higher than in controls.

PMID- 9148174
TI  - [The Landau-Kleffner syndrome. SPECT and EEG investigations].
AB  - Four children (three boys and one girl) with acquired epileptic aphasia (the
      Landau-Kleffner syndrome) have been observed in the Department of Developmental
      Neurology University of Medical Sciences in Poznan. We present the dynamic of
      clinical symptoms and fluctuations in EEG studies. The changes in the brain in
      single photon emission computed tomography (SPECT) during remission of clinical
      symptoms are discussed.

PMID- 9148175
TI  - [Myasthenia preceded by dysphonia. Clinical and electrophysical study].
AB  - The solely dysphonia symptom as atypical and relatively rare onset of myasthenia
      gravis is difficult to diagnose. We present 11 cases of myasthenia, where
      dysphonia was one and only one symptom of illness during several months to
      several years. The evidences of dysphonia were the fatigability and nasality of
      speech, as well as chronic hoarseness. The diagnosis of myasthenia was very
      difficult in this period and was often preceded by lengthy laryngological and
      neurological examination. In our paper we present the criteria proper for
      myasthenia diagnosis in which repetitive electrostimulation test and high
      sensitive SFEMG method are used.

PMID- 9148176
TI  - [Craniopharyngioma in childhood. Significance of the extent of surgical resection
      and adjuvant megavoltage irradiation for event: free survival].
AB  - A series of 81 children with craniopharyngiomas is presented. All patients were
      operated on between 1981 and 1992. According to the applied treatment the
      presented group was divided into three distinct categories. 28 patients underwent
      what was considered by the surgeon to be total excision of their tumour, 27 bad
      partial excision, in the rest 26 children partial excision of the tumour was
      followed by local rtgtherapy. The impact on the outcome, the statistically
      estimated probability of event-free survival, following different type of applied
      treatment was the main aim of this study. The 5- and 10-year actuarial recurrence
      free survival rate were 78% and 52% respectively, for total removal group, versus
      46% and 28% for partial removal, and 49% and 18% for partial removal followed by
      megavoltage irradiation. The study show a statistically significant advantage for
      radial surgical removal of childhood craniopharyngioma in event free survival. It
      is emphasized that total resection using modern diagnostic and surgical methods
      is the mainstay for childhood carniopharyngioma. Nearly 87% of pediatric
      craniopharyngiomas can be totally resected.

PMID- 9148177
TI  - [Contribution to the microanatomy of the proximal part of the arteria centralis
      longa (Heubner's artery)].
AB  - The anterior communicating artery complex is one of the most frequent
      intracranial aneurysm sites. Pterional craniotomy is the usual way to expose this
      region. While exposing of the aneurysmal dome, the posterior part of the gyrus
      rectus is frequently resected. In this stage of the procedure and later during
      clipping of the aneurysm, the surgeon's manipulation is closely related to the
      proximal part of the Heubner's artery. This vessel feeds important structures in
      the region of the basal ganglia. The anatomy of the Heubner's artery was
      described by many authors. However the intraoperative identification of this
      artery is still not clear. Therefore we performed detailed microanatomical
      investigation of the proximal part of the Heubner's artery in 40 brain
      hemispheres. It was found that during resection of the posterior part of the
      gyrus rectus two arteries are exposed. The recurrent Heubner's artery runs
      posteriorly to the gyrus rectus. The second artery runs on the medial and
      inferior surface of gyrus rectus supplying cerebral cortex. This artery
      frequently originates from the A1/A2 junction or the proximal part of the A2
      segment of the anterior cerebral artery. Because of it, this cortical artery is
      difficult to distinguish from the recurrent Heubner's artery. This artery can
      branch out from the recurrent Heubner's artery or the frontopolar artery. In
      conclusion, the greatest probability of the injury to the recurrent Heubner's
      artery may occur during resection of the posterior part of the gyrus rectus.

PMID- 9148178
TI  - [Intraoperative ultrasonography of brain tumors].
AB  - The 6-years results are described of intraoperative ultrasonic imaging of the
      brain tumors and are compared with the results of preoperative computerized
      tomography. On the basis of 169 cases it was shown that the lesions well visible
      in preoperative CT (with or without contrast) were also well delineated in USG.
      In cases of presence in CT with or without contrast of extensive isodense or
      hypodense area, USG could localize in all patients the tumor with suggestion of
      its morphology. Intraoperative ultrasonic investigation is a valuable method
      supplementing preoperative diagnostic procedures, facilitating the localization
      of isomorphic tumors, reducing brain traumatization and making possible control
      of radical removal of the lesions.

PMID- 9148179
TI  - [The blood-brain barrier. I. Histology. Physiology. Embryology. Transport].
AB  - The concept of blood-brain barrier (bbb) arose in the beginning of the 20th
      century after report that the dyes injected intravenously did not appear in the
      brain. The idea and definition of bbb has been changed many times since then. We
      present current opinion concerning bbb, its histology, embryology, ultrastructure
      and function on the ground of a review of the recent literature.

PMID- 9148180
TI  - [Myasthenia in an epileptic patient].
AB  - The author described a case of myasthenia and epilepsy in a female aged 36 years.
      The relationship between myasthenia and epilepsy was discussed. The additional
      factor which made the diagnosis difficult is bilateral deafness.

PMID- 9148181
TI  - [Unusual subclavian steal syndrome].
AB  - A case of unusual subclavian steal syndrome in a 50-years-old man without
      vertebro-basilar deficiency symptoms is reported. The lack of typical symptoms
      was caused by an uncommon collateral between the left vertebral and the left
      external carotid artery. The subclavian steal syndrome was revealed while
      diagnosing right hemiparesis which was the main cause of hospitalization.

PMID- 9148182
TI  - [Multifocal astrocytoma diagnosed by peroperative ultrasound scanning].
AB  - A multifocal astrocytoma, an uncommon cerebral lesion is presented. This case is
      particularly interesting because it was diagnosed by peroperative ultrasound
      scan. The epidemiology and the diagnostic procedure for multifocal gliomas is
      discussed.

PMID- 9148183
TI  - [Interhemispheric extracranial and intracranial tumor of parietal area
      (chondromyxoid fibroma) in a 13-year-old child with 7 years of follow-up].
AB  - A case of extra-intracranial, parietal chondromyxoid fibroma in a 13-year old
      girl operated successfully and followed by 7-years observation is presented.
      Apart from infrequent occurrence of the tumour diagnostic difficulties due to
      atypical cranial location are emphasized.

PMID- 9148184
TI  - [Cases of posterior inferior cerebellar artery aneurysms].
AB  - The authors described two cases of aneurysms of the posterior inferior cerebellar
      artery (PICA) successfully operated on. The possibilities of surgical approaches
      and methods of obliteration of the aneurysm and review of PICA aneurysms in the
      literature are presented.

PMID- 9148186
TI  - [Homolateral pyramidal disorders].

PMID- 9148185
TI  - [Report on satellite symposium on interferon beta therapy in multiple sclerosis,
      Newcastle on Tyne (England), June 26, 1996].

PMID- 9148187
TI  - [Doubtful Babinski reflex and the Szapiro method].

PMID- 9148188
TI  - Proceedings of the 1st Conference of Polish and Israeli Neurological Societies.
      Warsaw, Poland, 17-18 May 1995.

PMID- 9148189
TI  - Visuomotor sensitivity for shape and orientation in a patient with visual form
      agnosia.
AB  - We have previously demonstrated that a patient with visual form agnosia (DF), who
      is unable to report the orientation or size of visual targets, can nevertheless
      use these same visual attributes to control motor acts. In the first of three new
      experiments, we found that DF is able to grasp everyday tools and utensils
      proficiently (i.e. with a well-formed hand posture) but has difficulty in
      visually selecting the correct part of the object to grasp (e.g. the handle) for
      subsequent use of that object. A second experiment revealed that DF's visuomotor
      system is able to adjust concurrently to variations in both the size and
      orientation of target objects; when these visual attributes were both varied, she
      adjusted both her grip aperture and the orientation of her hand well in advance
      of target contact. These spared visuomotor abilities do not seem to extend to
      shape processing per se, however. In the final experiment we found that DF was
      insensitive to changes in the orientation of a cross-shaped object, where no
      single principal axis could be extracted to control orientation of the grasp.
      These observations extend our knowledge of DF's residual visuomotor abilities,
      and suggest limitations on the visual processing capacities of the human dorsal
      stream.

PMID- 9148190
TI  - Semantic category priming in the left cerebral hemisphere.
AB  - The representation of semantic codes in the cerebral hemispheres and the
      interhemispheric communication of these codes, was investigated in two priming
      experiments where prime and target words were independently projected to the left
      or right visual fields (LVF or RVF). Nonassociated category exemplars were
      employed as related pairs in a lexical decision task and separated by a stimulus
      onset asynchrony of 250 msec in Experiment 1 and 450 msec in Experiment 2. Both
      experiments obtained priming effects when primes and targets were both projected
      to the RVF, but not the LVF. Semantic category primes projected to the RVF also
      facilitated responses to LVF targets, but no LVF-RVF priming was obtained. This
      suggests that semantic category information is relayed from left to right
      hemisphere, but not vice versa. The results are consistent with the view that
      semantic categories are represented in the left hemisphere.

PMID- 9148191
TI  - Hemispheric specialization for discourse reports of emotional experiences:
      relationships to demographic, neurological, and perceptual variables.
AB  - This study examined hemispheric specialization for discourse reports of emotional
      and nonemotional experience in 16 right-brain-damaged (RBD), 16 left-brain
      damaged (LBD), and 16 demographically-matched normal control (NC) right-handed
      adults. Patient groups did not differ on etiology, months post-CVA onset, and
      intrahemispheric lesion location. Subjects were requested to produce monologues
      about positive and negative emotional and nonemotional experiences. The lexical
      content of written transcriptions of these monologues was later rated for
      "emotionality" by naive judges. Overall, RBDs described experiences with less
      emotional intensity than did NCs and LBDs, providing support for right hemisphere
      involvement in lexical emotion. Although the RBDs in the current study
      demonstrated similar patterns of deficits in a prior study [9] on tasks involving
      lexical emotional perception, there were no significant relationships between the
      current measures of emotional expression and the previous measures of emotional
      perception. Finally, the expression and the perception data were examined with
      respect to intrahemispheric factors. Among the brain-damaged subjects,
      subcortical structures were more involved in reports of emotional experience, and
      cortical structures were more involved in the perception of emotion.

PMID- 9148192
TI  - Semantic and episodic memory in aphasia.
AB  - Within the framework of the distinction between episodic and semantic memory, it
      has been argued that these two memory Systems are organised in a hierarchical
      way. The hierarchical hypothesis assumes that episodic memory is a specific
      subsystem of semantic memory and therefore implies that episodic memory cannot
      exist without semantic memory. If this hypothesis is correct, it should be
      expected that (episodic) yes/no recognition performance would improve in patients
      with preserved semantic memory, following semantic encoding. In the present study
      we investigated the influence of semantic encoding on recognition memory
      performance in a population of 28 aphasic patients (AA) and 14 normal controls
      (NC). Experiment 1 considered recognition memory for semantically unrelated
      items, whereas Experiments 2 and 3 assessed recognition memory for semantically
      related items. In Experiment 3, but not in Experiment 2, subjects were explicitly
      instructed to make a semantic association between the items. AA were impaired,
      compared to NC, only on the recognition memory performance of Experiment 1. The
      ability to make a semantic association between two items was significantly and
      positively correlated to the ability to recognise, in a subsequent test, those
      same items. A further analysis showed that patients who were impaired on the
      semantic association task did significantly worse on the recognition task of
      Experiment 3 than NC and than patients who were unimpaired on the semantic
      association task. These findings are discussed in the context of memory deficits
      in aphasia and interpreted as giving support to the view that episodic memory for
      an item is affected by the level of semantic awareness of that same item.

PMID- 9148193
TI  - Visual illusion and action.
AB  - The role of allocentric cues on movement control was investigated in the present
      study. Pointing movements directed to the more distant vertex of closed and open
      configurations of the Muller-Lyer illusion, as well as to the vertex of control
      lines, were studied in four experimental conditions. In the first (full-vision
      condition) subjects saw both stimulus and their hand before and during movement,
      in the second (non-visual feedback condition) they saw the stimulus, but not
      their hand during movement. In the two remaining conditions (no-vision
      conditions) vision of the scene and the hand was precluded. Pointing was executed
      0 sec (no vision 0 sec delay condition) or 5 sec (no-vision 5 sec delay
      condition) after the light was switched off. The Muller-Lyer illusion affected
      pointing kinematics with respect to the control lines. Subjects undershot and
      overshot the vertex location, respectively, of the closed and open configuration.
      Correspondingly, the entire kinematics were changed. The main result was,
      however, a gradually increasing effect of the perceptual illusion when pointing
      was executed from memory compared to the full-vision condition. These data are
      discussed according to the hypothesis that the system underlying visual
      perception in the allocentric frame of reference and that involved in motor
      action can functionally interact. The strength of this interaction depends upon
      the efficiency of the egocentric frame of reference by which motor actions are
      constructed.

PMID- 9148194
TI  - Nonverbal visual attention, but not recognition memory of learning, processes are
      impaired in motor neurone disease.
AB  - Pathology outside the motor system is being increasingly recognised in motor
      neurone disease (MND) and up to 3% of patients may have overt dementia of frontal
      lobe type; it is not clear whether milder cognitive disturbance is a more
      frequent feature of the disease. Standard neuropsychological testing can be
      difficult in MND and we therefore used the microcomputer-controlled Cambridge
      Neuropsychological Test Automated Battery (CANTAB), which allows accurate
      assessment in the presence of motor and bulbar dysfunction. The results of
      subtests evaluating nonverbal visual attention, recognition memory and learning
      from a large (n = 50) group of patients with MND compared to normal (n = 27) and
      neurological disease (n = 23) control groups are presented in this report. The
      MND group showed significant impairment in a focal attention (visual search)
      task, but no deficits in memory or learning. Inspection of the visual search data
      showed that up to a quarter of the MND patients scored two or more standard
      deviations below the mean control score. It is suggested that this reflects
      pathology in fronto-striatal circuitry.

PMID- 9148195
TI  - Effects of focal brain lesions on visual problem-solving.
AB  - In this study, the relative contributions of different brain regions to visual
      problem-solving were explored using a new test of divergent thinking. Seventy
      three patients with focal brain lesions and 20 normal control subjects performed
      a set of matchstick problems, similar to those described by Guilford [15] as a
      measure of adaptive flexibility. For each problem, subjects were to demonstrate
      as many ways as possible of removing a particular number of sticks from a two
      dimensional geometric design to achieve a specified resultant shape. Patients
      with left temporal-occipital, right temporal-occipital, or left frontal lesions
      displayed no significant difficulty. Evidence of general deficiencies in the
      ability to manipulate this visual material was seen in patients with parietal
      and/or central-area lesions (right worse than left). In contrast, patients with
      right frontal-lobe damage demonstrated a selective impairment in the ability to
      shift strategy. The results confirm the importance of the right suprasylvian
      region in the ability to process and act on visual information. They also provide
      evidence of the specific role played by the right frontal lobe, and particularly
      the ventral region, in permitting a flexible approach to visual problem-solving.

PMID- 9148196
TI  - Neuropsychological aspects of frontal lobe epilepsy.
AB  - While most neuropsychological studies in focal epilepsies are concerned with
      temporal lobe epilepsy (TLE), only few investigations aim cognitive functioning
      in unresected patients with frontal lobe epilepsy (FLE). Following functional
      models arising from lesional studies, we evaluated patients with TLE (21 left, 17
      right) and FLE (6 left, 17 right) with respect to attention and speed, motor
      coordination, verbal/nonverbal fluency, concept formation, response inhibition,
      anticipatory behavior and memory span. The following results were obtained. When
      compared to TLE, FLE was associated with significantly poorer results in almost
      all tests, fluency tests being the exception. No group differences were found
      with respect to the lateralization of the epileptic focus or the presence or
      absence of cerebral lesions. Factor analysis of the tests indicated that
      different subfunctions (speed, STM, motor coordination, response maintenance and
      inhibition) were assessed. A particular cognitive pattern of impaired motor
      coordination or response inhibition appeared to be characteristic for patients
      with FLE.

PMID- 9148197
TI  - Biased attention and the fused dichotic words test.
AB  - This study examines the effect of biased attention on the fused dichotic words
      test (FDWT) and the CV syllables dichotic listening test (CVT). Eight males and
      eight females were given both tests with two different instructions: to direct
      attention to the left ear (DL), or to the right ear (DR). These instructions led
      to highly significant differences in response on the CVT, but only a marginal
      shift in performance on the FDWT. While the FDWT is not completely unaffected by
      attentional manipulations, it is far less influenced by such effects than the
      CVT. This indicates that subject-initiated shifts of attention are much less
      likely to affect performance on the FDWT than on other dichotic tests and makes
      it a more valuable task to assess cerebral speech lateralization.

PMID- 9148198
TI  - A pop-out induced extinction-like phenomenon in neurologically intact subjects.
AB  - A series of tachistoscopic search experiments was performed to investigate
      variations of distractor effects dependent on the relative position and salience
      of target and distractor. It was found that highly salient (pop out) items
      distracted search for less salient (conjunction) targets and vice versa. However,
      only the effect of pop-out distractors was lateralized when paired with a
      contralateral target, RVF-distractors leading to a stronger latency increase.
      With unimanual response, this effect was stronger in the right hand. When the
      distractors were presented in the same visual halffield (VF) as the targets,
      effects were of comparable size in both VF.

PMID- 9148199
TI  - Does recognizing orally spelled words depend on reading? An investigation into a
      case of better written than oral spelling.
AB  - In this study we describe an investigation into the residual spelling skills of a
      patient (BRK) with a deep dysgraphia. His written spelling was significantly
      superior to his oral spelling and he had grave difficulties in recognizing orally
      spelled words. In addition, his impairment in recognizing orally spelled words
      was qualitatively very similar to his difficulties in oral spelling. In contrast,
      he could read and repeat the stimuli he could no longer spell. It seems therefore
      that, recognizing orally spelled words is dependent on the same procedures used
      in spelling rather than in reading. It is argued that BRK's discrepancy between
      oral and written spelling reflects a deficit in accessing a letter name code
      which translates abstract graphemic representations into letter names. In
      addition, it is suggested that the letter name code has an additional
      synthesizing function that is involved both in checking self-generated oral
      spellings and in recognizing orally spelled words.

PMID- 9148200
TI  - Selective loss of verbal imagery.
AB  - This single case study of the ability to generate verbal and non-verbal imagery
      in a woman who sustained a gunshot wound to the brain reports a significant
      difficulty in generating images of word shapes but not a significant problem in
      generating object images. Further dissociation, however, was observed in her
      ability to generate images of living vs non-living material. She made more errors
      in imagery and factual information tasks for non-living items than for living
      items. This pattern contrasts with our previous report of the agnosic patient,
      M.S., who had severe difficulty in generating images of living material, whereas
      his ability to image the shape of words was comparable to that of normal control
      subjects. Furthermore, with regard to the generation of images of living compared
      with non-living material, M.S. shows more errors with living than nonliving
      items. In contrast, the present patient, S.M., made significantly more errors
      with non-living relative to living items. There appear to be two types of double
      dissociation which reinforce the growing evidence of dissociable impairments in
      the ability to generate images for different types of verbal and non-verbal
      material. Such dissociations, presumably related to sensory and cognitive
      processing demands, address the problem of the neural basis of imagery.

PMID- 9148201
TI  - Perceptual priming in Alzheimer's and Parkinson's diseases.
AB  - The present study focused on perceptual identification priming (implicit memory)
      in early stages of dementia by studying demographically and cognitively matched
      patients with Alzheimer's disease (AD) and Parkinson's disease (PD). The AD and
      PD groups performed normally on perceptual identification priming, whereas their
      explicit recognition memory was equally impaired compared to normal controls.
      These results imply that priming in perceptual identification relies on the
      perceptual memory system which can resist not only impairments of explicit memory
      but also widespread cognitive deterioration induced by the neurodegenerative
      processes in AD or PD.

PMID- 9148202
TI  - [Prosthetic bilateral laparoscopic hernioplasty. Extra-peritoneal approach].
AB  - The use of prosthetic mesh in inguinal hernia repairs is becoming increasingly
      popular. In recent years different laparoscopic procedures for prosthetic repair
      of inguinal hernias have been developed. The authors describe their initial
      experience with a totally extra-peritoneal prosthetic approach in laparoscopic
      repair of bilateral inguinal hernias. From November 1993 to May 1994, ten
      consecutive patients with bilateral primary inguinal hernias underwent
      laparoscopic repair under general anesthesia. A totally extra-peritoneal approach
      has been performed beginning through a 2 centimeter vertical midline sub
      umbilical incision. Two additional trocars have been inserted on the midline: a
      10/12 mm one halfway between the umbilicus and the pubis and 5 mm one 2 cm above
      the pubis. Average operative time was 141 minutes. Two cases were converted to
      traditional open Stoppa procedure because of holes made in the peritoneum during
      blunt dissection of the hernia sac. In the remaining 8 cases a polypropylene mesh
      of about 8 cm in height and 13 cm in length have been placed on each hernia site.
      No major complications have been observed and recovery was quick in all cases. In
      conclusion we think that laparoscopic hernia repair through a totally extra
      peritoneal approach is technically feasible for general surgeons trained in
      laparoscopic surgery. Nevertheless the operation in costly and the patient's
      benefit in terms of rapid recovery, complications and recurrences has not yet
      been demonstrated in controlled prospective trials.

PMID- 9148203
TI  - [Prosthetic repair of inguino-crural hernia using Rives technique].
AB  - The authors report their experience with Rives procedure, a prosthetic repair of
      groin hernias using preperitoneal sutured mesh by parainguinal access. This
      operation is not technically easy to perform and is usually done out of necessity
      in cases with higher risk of recurrence because of systemic factors of chronic
      abdominal high pressure and/or of local factors of risk, when there are
      contraindications to operations like Stoppa procedure. Our series report 38
      patients operated upon on 5 years, with incidence of 5.8% overall hernias
      repaired in the same period. 33 are males, 5 females, with average age of 60.5
      years. Mean time required for the operation is 94 minutes (range 55'-130'). About
      postoperative complications we complain of one testicular atrophy, but none
      infections. Follow-up range is 9-50 months (average 23.2 months) for 30 patients
      operated more than one year ago. All but one were revisited after almost 12
      months. No recurrences were detected.

PMID- 9148204
TI  - [Laparoscopic versus laparotomic adrenalectomy: preliminary experiences].
AB  - The authors report their experience about laparoscopic surgery in the treatment
      of adrenal tumours. Three laparoscopic right adrenalectomies were performed. From
      a comparison with five open adrenalectomies, microinvasive surgery is more
      advantageous than traditional management: recovery is earlier, incisions are
      smaller, post-operative discomfort is less, physiologic functions recover in a
      short time, return to full professional activity in one week.

PMID- 9148205
TI  - [Reconstruction using pedicle and free flaps in partial or total resections of
      the hypopharyngeal-esophageal tract].
AB  - Modern surgical treatment of cancer of the hypopharyngo-esophageal cannot be
      conditioned by the reconstructive procedures. Reconstructive options are based on
      the size and position of the defect in this important anatomical region.
      Currently the reconstruction of the hypopharyngo-esophageal tract allows a rapid
      and suitable restoration of the vital functions, a low morbidity and shortened
      hospital stay. The purpose of this study was to compare the various
      reconstructive approaches in terms of morbidity and functional results. Between
      January 1990 and June 1994, 17 patients with hypopharyngo-esophageal tract
      malignancies and one with a stenosis received treatment. The reconstructive
      procedures included 19 flaps: five myocutaneous pectoralis major flaps, one
      myocutaneous trapezius flap, five deltopectoral flaps, one radial forearm free
      flap and seven free jejunal grafts. There were six complications: one total
      necrosis and two stenosis in the free jejunal grafts group, one partial necrosis
      and one dehiscence in two myocutaneous pectoralis major flaps and one stenosis in
      a deltopectoral flap. Based on our studies, we believe that the free jejunal
      graft is the first choice for total reconstruction of the hypopharyngo and
      cervical esophageal tract. However the radial forearm free flap is certainly a
      valid solution for subtotal hypopharyngo-esophageal reconstruction. Pedicled
      flaps and particularly the myocutaneous pectoralis major flaps are a good
      alternatives for limited reconstructions (< 50%) of the hypopharyngo-esophageal
      tract.

PMID- 9148206
TI  - [Prosthetic materials in surgery of esophageal cancer. Personal experience].
AB  - Even if the incidence of esophageal carcinoma is low (25% in comparison to rectal
      cancer) the total mortality of this disease is very high (superior to rectal
      cancer itself according to Am.Ca.SO. data). That's because of the high number of
      non resectable patients when they are first seen by the physician for dysphagia.
      The aim of the treatment in such cases is to permit a sufficiently good intake to
      the patient avoiding non-acceptable gastrostomy. The authors report their
      experience using esophageal prosthesis (27 cases). Mortality rate was 3.7% distal
      migration 7.4%. They report 3 cases of "minor" complication (11.1%). The mean
      survival was 5.3 months, the quality of life was satisfactory in all treated
      cases.

PMID- 9148207
TI  - [Adenomatous tissue in colorectal carcinomas: clinical significance and probable
      histogenetic implications of morphological differences].
AB  - In this study we tested the hypothesis that colorectal cancers containing adenoma
      (CCA) could be a different entity from colon cancers without adenoma (CSA).
      Clinical data, histologic preparations of operative specimens and survival of 210
      patients who underwent resective surgery for colorectal cancer were studied.
      Adenomatous tissue within the cancer was found in 62 of 210 carcinomas (CCA), the
      other 148 cancers were lacking adenomatous features (CSA). CCA occurred more
      frequently in female patients (p = 0.003). Synchronous adenomas were detected in
      the resected colon of 19 out 62 CCA and of 24 out 148 CSA (p = 0.04). CCA showed
      the extent of intraparietal spread (p = 0.001), grade (p = 0.007) and stage (p =
      0.004) lower than CSA. These characteristics also appeared statistically related
      to size of the cancers. The adenomatous tissue within CCA was tubular in 4 cases,
      tubulo-villous in 34 and villous in 24 cases. The villous histotype was
      statistically related to the older age of patients (p < 0.0001), larger cancer
      size (p = 0.01), presence of synchronous adenomas in the resected colon (p =
      0.02) and higher histologic grade of the cancer (p < 0.05). Patients with CCA
      evidenced a higher 5-year survival rate (p = 0.02). Our results evidence
      epidemiologic, clinical and pathologic differences between CCA and CSA and
      suggest a possible double histogenesis of colon cancer.

PMID- 9148208
TI  - [Surgical treatment of liver metastases of breast carcinoma. Our experience].
AB  - The authors report their experience in the surgical treatment of breast cancer
      liver metastases. Although with a restricted number of cases (4 patients), the
      short-term results are satisfactory; this is in agreement with the literature.
      The survival of those patients treated with a loco-regional approach to
      metastases (chemotherapy and surgery), is longer than one obtained using systemic
      chemotherapy. This is still an open question requiring further experience.

PMID- 9148209
TI  - [Perioperative complications in traditional surgery of the rectum].
AB  - The authors report their experience of 136 operations for rectal neoplasms, on
      all of 652 colo-rectal neoplasms, treated from January 1987 to May 1994. In
      detail the perianastomotic complications have been tested after "traditional"
      rectal operations: Anterior Resection (RA), Abdomino-perineal amputation (AAP)
      and Hartmann's procedure. A series of 24 AAP (18%), 81 RA (60%) and 7 Hartmann's
      procedure have been considered; conversely 18 final and palliative colostomies
      (13%) and 7 trans-anal operations haven't been taken in to account. Perioperative
      mortality was comparatively reasonable: 2.7%. No patient died after AAP. The most
      common complication proved to be anastomotic leak (17.3%), after RA; otherwise
      the rate of further complications was very moderate. It is feasible to avoid
      anastomotic leaks, by carrying out a temporary colostomy.

PMID- 9148210
TI  - [Reconstructive oncologic surgery of the head and neck. Morbidity and comparative
      results of conventional and myocutaneous flaps].
AB  - The authors analyzed the data obtained from their experiences in extensive head
      and neck resections, and, reconstructive treatments using myocutaneous and
      conventional flaps. They tried to evaluate comparatively the reconstructive
      approach, in terms of morbidity and functional results. The 145 cases of advanced
      had and neck cancer, treated from January 1990 to January 1994, were considered
      in this study. The reconstructive procedures consisted of 193 flaps. In this
      study, 106 were myocutaneous flaps (pectoralis major or trapezius flap); 72 were
      conventional flaps (fasciocutaneous, cutaneous or muscular only) and the
      remainder were 15 free flaps. The morbidity related to both flap procedures had
      been low: 33% in myocutaneous flaps versus 11% in conventional flaps. This report
      demonstrated the versatility, usefulness, and reliability of both kinds of these
      reconstructive procedures, especially in intra-oral reconstruction. The expected
      morphological and functional results were quite encouraging in terms of
      swallowing and speech.

PMID- 9148211
TI  - [Closed abdominal injuries].
AB  - The treatment of blunt abdominal traumas remains controversial because of the
      difficult diagnosis; the authors review the international literature and express
      their five years (1990/1994) experience, constituted of sixty three patients,
      explaining the motivations of their diagnostic and therapeutic behaviours and the
      problems they met and how they succeed in resolving them. The authors remark the
      best way to face blunt abdominal trauma. Only the coordination among all the
      emergency care team involved can solve the problems.

PMID- 9148212
TI  - [The post-cholecystectomy syndrome. Evaluation of symptomatology using Tc-99m
      HIDA sequential hepatic scintigraphy (cholescintigraphy)].
AB  - The authors comment the data from research on 70 patients with post
      cholecystectomy syndrome, using cholescintigraphy HIDA 99mTc to evaluate the
      relation ship between symptomatology (see classific.) and duodenogastric reflux
      entity. Cholescintigraphy seems to be a valid clinical means, especially for a
      correct indication to endoscopy.

PMID- 9148213
TI  - [Pre- and postoperative color Doppler ultrasonography of myocutaneous flaps in
      reconstructive surgery of the breast].
AB  - The authors present their experience in the study of blood supply of flaps. The
      machine used to study both pre and postoperatively the myocutaneous flap is the
      echo-color Doppler, a brand new device which has recently been used in
      investigating the morphology and the blood supply. The use of such method has
      provided us with the following information: detailed ultrasound structure of the
      skin, subcutaneous and muscular tissues of the examined flap; localization of
      vessels within the flap; size of the vessel in its whole length; quality and
      speed of both the arterial and venous flow. Such information is very important
      for the surgeon to plan in detail the reconstruction by knowing the blood supply
      of myocutaneous flap.

PMID- 9148214
TI  - [Risk indices in geriatric surgery: ASA index versus Reiss index].
AB  - The use of the Risk Index in surgery is aimed to plan surgical strategy in order
      to achieve a better postoperative prognosis. This is especially true in geriatric
      surgery where the ASA Index and, more recently, the Reiss Index are widely
      employed. Since the mentioned Risk Indices are calculated on the basis of
      different factors, in this study we compared the two Risk Indices with the aim of
      verifying which index offers better prognostic indications. 210 patients, aged
      over 70 years, undergoing surgical treatment, were investigated. The patients
      were grouped according to the ASA and Reiss Indices. The ASA Index showed good
      correlation only with postoperative mortality. The three classes of Reiss Index
      showed a significant correlation with the incidence of post-operative morbidity
      and mortality (p.o. morbidity: 7.1%, 21.5%, 30.3%; p.o. mortality; 1.7%, 9.2%,
      24.2% -Chi 2 = 20.7; p < 0.001). Our results support the hypothesis that Reiss
      index offers better prognostic evaluation of postoperative outcome, suggesting
      its use in assessing postoperative prognosis in geriatric patients. In addition,
      our observation confirms the criticism reported of the ASA Index, merely
      considered as an indicator of health status regardless of surgical treatment. In
      conclusion, routine preoperative evaluation of the Reiss Index should be advised
      in geriatric patients with the aim to forecasting surgical risk in the first
      place, and them modifying operative strategy in order to improve postoperative
      results.

PMID- 9148215
TI  - [Diverticular disease and its treatment].
AB  - Diverticular disease of the colon is being seen with increasing frequency. Not
      infrequently, the first attack of diverticulitis may result in serious and
      potentially fatal complications. A period of observation and conservative
      management is necessary to determine the outcome of a particular attack.
      Approximately 30% of symptomatic patients require surgical intervention.
      Controversy still surrounds the appropriate operative approach to be employed in
      the management of diverticular disease, moreover when it presents with a
      complication. In general, resection is the procedure of choice for perforating
      diverticulitis. There is an emerging role for down-staging interventions in the
      recent literature; with few exception, there is no role for three-stages
      procedure for diverticular disease. In the setting of stage I or stage II disease
      (Hinchey classification) primary resection with anastomosis is safe and should be
      performed. Proximal colostomy formation may be carried out at the discretion of
      the surgeon if warranted by such local circumstances as contiguous inflammation
      or macroscopic contamination. For patients with stage III and stage IV disease
      endcolostomy with Hartmann closure of the rectum is the procedure of choice,
      although anastomosis with proximal stoma may prove to be an acceptable
      alternative. We reviewed the changing patterns in the operative treatment in 46
      patients admitted to our Division for perforated diverticulitis. We performed the
      resection with anastomosis in 39 patients with perforation at the II stage; in 7
      patients with generalized peritonitis (stage III-IV by Hinchey) we preferred
      Hartmann intervention in 4 cases and the three-stages procedure in 3 cases. We
      had no death at all. From 1979 to 1994 we noticed an increasing use of down
      staging procedures.

PMID- 9148216
TI  - [Video laparoscopic cholecystectomy in situ viscerum inversus totalis].
AB  - Situs viscerum inversus totalis is a rare condition with a genetic predisposition
      that is autosomal recessive. We present a case in an elderly patient with
      transposition of the viscera and cholelithiasis, who was successfully treated
      with laparoscopic cholecystectomy. This paper further expands the application of
      this technique and shows that they can be safely and effectively applied in the
      setting of situs viscerum inversus totalis, although attention must be paid to
      the details of left-right reversal.

PMID- 9148217
TI  - [Subcutaneous emphysema during laparoscopy. A case report].
AB  - Diagnostic and therapeutic laparoscopy is a safe procedure, which, however, is
      not without complications. In this article, we report a case of subcutaneous
      emphysema, as a consequence of pneumoperitoneum, during laparoscopic
      cholecystectomy. The mechanism for the development of this complication and its
      management are discussed.

PMID- 9148218
TI  - [Anomalous implantation of the appendiceal base. A case report].
AB  - The authors report a case of anomalous appendicular implantation observed in a 17
      year-old male. The appendix was not found in its usual site, but upon the antero
      lateral wall of ascending colon, 15 cm from the junction of the taenia of caecum.
      A partial mobilization of caecum was required for appendectomy. By a review of
      recent bibliography this anomaly seems very unusual considering the poor number
      of reports in literature. The anatomy and embryology of the vermiform appendix
      are briefly presented, and at the same time the possible pathogenetic hypothesis
      of this anomaly, such as described by other colleagues. The authors underscore
      how, knowledge of another case report, in their experience, suggested to search
      for appendix in an unusual site, before concluding for an appendicular agenesis.

PMID- 9148219
TI  - [Diagnosis and treatment of gastrointestinal carcinoid. Report of a clinical case
      with duodenal site].
AB  - Carcinoid tumors are among the most frequently neuroendocrine neoplasms of the
      gastrointestinal tract. They occur more commonly as benign diseases but malignant
      ones can also be found. The peak age incidence varies with the location of the
      tumor, with appendiceal tumors being diagnosed at an overage of 36 years, whereas
      non appendiceal tumors are found typically in the fifth sixth decades of life.
      There is no sex predilection of the tumors. Most carcinoid tumors are found
      within the appendix (40-50%) or small intestine (25%). Less common sites include
      the rectum (15%), main bronchus (10%), duodenum (3-8%) and stomach (2%). Most
      carcinoid tumors are found incidentally at operation and cause no symptoms. If
      symptoms do occur, they can be either non specific include intermittent crampy
      abdominal pain, vomiting and distension caused by intestinal obstruction. The
      prognosis depends on the site of the tumor and its size. Most carcinoid tumors
      (75%) are less than 1 cm in size and only 5% are greater than 2 cm. The incidence
      of metastatic disease is related directly to the size of the tumor at all
      locations. Carcinoid tumor with size less than 1 cm give linfonodal metastasis
      only in 3-5%; the other with size over 2 cm give metastasis in the 70-75% of the
      cases. The 5-years survival for all carcinoid tumors are approximately 85%. Five
      years rate is higher (> 80%) in carcinoid tumors of appendix and rectum than in
      gastroduodenal, ileal and colonic neoplasm (< 60%). In this paper the authors
      report a case of malignant carcinoid of the duodenum.

PMID- 9148220
TI  - [Insulinoma. Clinical and surgical considerations concerning a case].
AB  - Insulinoma is the most common endocrine tumor of the pancreas. It arises from the
      beta-islet cells of Langerhans. Insulinomas synthesize and secrete insulin
      autonomously in the presence of low blood glucose levels, causing spontaneous
      hypoglycemia and characteristic clinical symptoms. The authors examined data the
      from the most important international research projects on this topic during the
      past 20 years. Insulinomas are rare, with an annual incidence of 0.5 per million
      population. Up to 90% patients have benign solitary pancreatic insulinomas.
      People of all ages can be affected with this neoplasm. The authors reported a
      case of a large insulinoma of the body and tail of the pancreas, with atypical
      psychic symptoms. A distal pancreatectomy with splenectomy was performed. No
      surgical complications occurred in the postoperative course. The psychic symptoms
      were emphasized with refusal of food. The patient underwent Parenteral Nutrition
      and was discharged 24 days after the operation. The surgical removal of the tumor
      permitted the patient to recover completely, with glucose and insulin blood
      levels in normal range.

PMID- 9148221
TI  - [Morgagni's hernia in infancy].
AB  - Morgagni's hernia is an uncommon type of diaphragmatic hernia fairly exceptional
      in pediatric age. A case of Morgagni's hernia, observed by chance in a 15-month
      old infant, is presented. The authors present the fundamental embryogenic stages
      of the diaphragm and stress the clinical manifestations and diagnostic procedures
      to reach the diagnosis, as well as the advantages of early treatment in order to
      prevent possible complications.

PMID- 9148222
TI  - [Surgical treatment of rhinophyma using dermo-epidermal graft. A case report].
AB  - Rhinophyma is a nosographical form that has always attracted attention, even
      among non-experts, owing to the marked aesthetic damage it often causes. Several
      types of surgery have been proposed for its treatment in an attempt to elaborate
      a technique that is easy to apply and guarantees satisfactory results in clinical
      and aesthetic terms. After a short review of the general aspects of the
      pathology, the authors illustrate the case of a patient with rhinophyma treated
      with a full thickness dermo-epidermic graft, and emphasise that this surgical
      solution, provided that the indications are correct, is still a valid
      alternative.

PMID- 9148223
TI  - [Brucellosis with osteo-muscular localization. A case report of a not rare
      pathological condition].
AB  - Brucellosis may show itself only through its bone and muscle complications,
      especially in the lumbar region, such as vertebral colliquation or psoas abscess.
      The authors describe a case of brucellosis (56 year old male, butcher) with
      lumbar bone and muscle involvement. The first symptom was a persistent pain of
      the right lumbar region, with irradiation to the homolateral leg. At admission
      the patient showed a lumbar cutaneous fistula with pus-like secretion. Quick
      diagnosis and therapy can prevent irreparable damage, even when the symptoms are
      silent.

PMID- 9148224
TI  - [Thrombosis of the renal artery of traumatic origin].
AB  - On the basis of a case study which was referred to their attention, the authors
      make a critical review of international literature on the physiopathological
      aspects and subsequent complications of renal artery trauma. The aspect that is
      most carefully evaluated refers to the types of therapeutic technique adopted by
      various authors in an attempt to resolve post-traumatic thrombosis whilst
      preserving kidney function. In view of the results obtained over the years and on
      the base of their own experience, the authors confirm the validity of
      angioplastic surgery, where possible, or nephrectomy in cases where renal
      function is excluded.

PMID- 9148225
TI  - [Meropenem (Merrem) vs imipenem/cilastatin in hospital treatment of intra
      abdominal infections. A multicenter study].
AB  - OBJECTIVE: To determine clinical and bacteriological efficacy and tolerability of
      meropenem and imipenem/cilastatin, given intravenously, in the treatment of intra
      abdominal infections in hospitalized patients. EXPERIMENTAL DESIGN: Open
      multicentre, randomized, parallel groups clinical trial, comparing meropenem and
      imipenem/cilastatin. ENVIRONMENT: Six Italian hospitals. PATIENTS: Eighty-six
      hospitalized patients, aged 16 or more, with intra-abdominal infections requiring
      parenteral antibiotic therapy, were randomized to two treatment groups (43 on
      meropenem, 43 on imipenem/cilastatin). Eighty-four patients completed the study
      and 2 were excluded from efficacy analysis. TREATMENT: Meropenem and
      imipenem/cilastatin were administered intravenously at 1 g TID. Dosage was
      reduced in patients with renal impairment. Mean treatment duration in clinically
      evaluable patients was 7.0 days in meropenem group and 7.6 days in
      imipenem/cilastatin group. MEASUREMENTS: Clinical efficacy evaluated at the end
      of the therapy and 2-4 weeks after. Bacteriological efficacy before, during, and
      immediately after the end or the modification of the experimental treatment. All
      adverse events were recorded. RESULTS: 42/43 (98%) patients on meropenem and
      39/41 (95%) on imipenem/cilastatin had satisfactory clinical response. In both
      groups bacteriological response was satisfactory in 26/27 (96%) evaluable
      patients. No statistically significant differences were found, both for clinical
      and bacteriological efficacy. Only two adverse reaction to study drug were
      observed (1 rash per treatment group). CONCLUSIONS: Meropenem, broad spectrum
      antibiotic with high stability to human renal DHP-1, given alone for the
      treatment of intra-abdominal infections is as effective and well tolerated as
      imipenem/cilastatin.

PMID- 9148226
TI  - [Comparison between torasemide and furosemide in the treatment of ascites in
      cirrhotic patients].
AB  - Twenty patients with cirrhosis and ascites were randomly divided in two groups to
      receive 20 mg/die of the new-loop-diuretic torasemide (T), and 50 mg/die of
      furosemide (F). All patients also received 200 mg/die of potassium canrenoate.
      Natriuretic and diuretic effects and consequent loss of weight were significantly
      better in the torasemide-group (T-group). Otherwise, loss of potassium and
      sodium/potassium ratio in urine were not significantly higher for T-group.
      Ammonium lowered with T and remained unchanged with F, but the difference was not
      statistically significant. No change was observed in blood-pressure, pulse
      frequency, electrolyte plasmatic levels, azotemia, creatininemia and serum
      albumin. A significant increase of diuresis was obtained from the fourth day of
      treatment onwards by replacing F with T in the F-group. The T-group maintained T
      for eight days just to evaluate its efficacy and tolerability in the middle term:
      diuresis kept efficient and no side-effects occurred. This trial showed that T
      was a good and handy drug for cirrhosis with ascites whether as an alternative to
      F, or as a sequential treatment.

PMID- 9148227
TI  - [Azithromycin combined with pyrimethamine in the treatment of neurotoxoplasmosis,
      in an AIDS patient].
AB  - We report one case of successful treatment of cerebral toxoplasmosis in acquired
      immunodeficiency syndrome (AIDS) with azithromycin combined with pyrimethamine.
      Toxoplasmic encephalitis had been diagnosed on the basis of multiple lesions
      exhibiting ring like contrast enhancement on double contrast Computed Tomographic
      (CT) scan of the brain. Thereby our patient had been treated with pyrimethamine
      25 mg/die, after an attack dose of 100 mg in the first day, and clindamycin 2400
      mg/die, because of sulfa-drug allergy, but clindamycin had to be discontinued
      because of rash development. At this point azithromycin, at a dose of 1000 mg/die
      for 21 days and 1500 mg a week for the following 50 days of follow-up, was added
      to pyrimethamine. Follow-up CT scan after 20 days of treatment (10 with
      clindamycin+pyrimethamine and 10 with azithromycin+pyrimethamine) revealed
      partial resolution of the brain lesions and subsequently (after 50 and 80 days of
      treatment) complete resolution.

PMID- 9148228
TI  - [Hemorheology in different types of obesity].
AB  - BACKGROUND: Obesity is a symptom of impaired fat metabolism, organs and system of
      which are: the liver where fat synthesis and oxidation occur and the adipose
      tissue with a storage function. Obesity in NIDDM, insulism and suprarenalism is
      due to an increased synthesis in triglycerides and their deposit in fat cells.
      Aetiologic factors of primitive obesity act on the fat tissue promoting
      lipogenesis (hypertrophic or hyperplastic action) and/or reducing fat release.
      METHODS: Thirty-two women suffering from obesity but without cardiovascular
      pathologies were investigated. Obesity degree and type were defined by the
      anthropometric method. The following tests were carried out: glycemia,
      insulinemia, C-peptide in OGTT, tryglicerides, cholesterolemia and cortisolemia.
      Plasma viscosity (V) and whole blood V were determined with rotational
      microviscosimeter; erythrocyte V and plasma-erythrocyte V were performed with
      double filtering method and values expressed in cP. Deformability was calculated
      as a ratio between viscosities determined with both filtering methods. RESULTS:
      On the basis of the type of obesity three groups were characterized: gynoid,
      intermediate and android. Rheological parameters are increased in all women:
      increase of plasmatic V, increase especially of erythrocytic viscosity with a
      considerable decrease in deformability. There are interesting differences among
      the three groups. CONCLUSIONS: The relationship between obesity and
      cardiovascular disease is well known and the early rheological impairment could
      be the factor linking both pathologies. Some factors involved in obesity, such as
      hyperglycemia and hyperinsulinemia, are also suspected of impairing hemorheology
      promoting changes in the microcirculation.

PMID- 9148230
TI  - [Cancer in the elderly. Clinico-epidemiologic considerations].
AB  - The elderly population is rapidly increasing in Western countries. Old age
      indirectly represents one of the most important risk factors for the development
      of neoplasias. In Italy in 1991 a total of 14,572 deaths from tumours were
      recorded, equivalent to 27% of all deaths; of these over 66% affected individuals
      aged over 65 years old. In the 65-74 age bracket mortality caused by tumour is
      the prime cause of death in Italy and is undergoing an exponential increase over
      time. The most frequently found tumours and above all the cause of the greatest
      number of deaths in the elderly population are lung cancer, prostate cancer,
      breast cancer, colorectal cancer, stomach cancer. To date the only weapon that
      has proved efficacious in some tumours (breast, colon-rectal, prostate, melanoma)
      is early diagnosis through screening and adequate treatment. The elderly are an
      extremely heterogeneous population and it is therefore not easy to provide
      guidelines that are applicable to the entire population. Firstly, it is important
      to provide more information in order to permit effective and targeted prevention.
      In order to fulfil this objective, structures offering the necessary equipment
      and skills will have to be create; training must be provided for personnel in
      this type of preventive medicine; lastly, the awareness of doctors towards this
      type of medicine must be increased by providing the correct information.

PMID- 9148229
TI  - [Serum protein changes in diabetes mellitus].
AB  - AIM: To evaluate the serum protein pattern in a wide sample of diabetic patients
      using the simple method of electrophoresis, identifying the characteristics for
      each condition and correlating the various components. EXPERIMENTAL DESIGN: A
      retrospective study was made using medical records. SETTING: The Institute of
      Clinical Medicine I at Palermo University Hospital during the years 1990, 1991
      and 1992. PATIENTS: 156 patients suffering from diabetes mellitus, of whom 68
      were Type 1 (IDDM) and 88 Type 2 (NIDDM). The latter were divided into non-obese
      (NO-NIDDM), obese (O-NIDDM) and "secondary failures" (SF-NIDDM) to oral
      hypoglycemic agents (receiving mixed treatment, TM-NIDDM, or insulin alone, I
      NIDDM). PARAMETERS: In addition to personal and anthropometric data and clinical
      data, in particular dysmetabolic data, an electropherogram was performed in each
      patient. RESULTS: Higher serum albumin concentrations were found in patients with
      IDDM, NIDDM compared to I-NIDDM, with an overall inverse correlation between the
      duration of diabetes and albumin serum levels. On the contrary, serum levels of
      alpha-2 globulins were higher in I-NIDDM patients compared to IDDM, and directly
      correlated with the age and duration in the overall series. beta-globulin levels
      were lower in IDDM patients compared to all other groups, and were directly
      correlated with age and body mass index (BMI) in the overall series. No
      statistical significance or correlation was found between the two groups in
      relation to alpha 1 and gamma-globulins. CONCLUSIONS: The study showed a
      characteristic serum protein pattern for each group of diabetic patients
      examined, analysing the role of insulin but also the duration and typical
      pathological events of the natural history of diabetes on protein metabolism, not
      only with regard to the amino acid metabolism but also on the distribution of
      circulating proteins.

PMID- 9148231
TI  - [Solitary primary cerebral echinococcosis. Report of a case].
AB  - INTRODUCTION AND AIMS: Echinococcosis is a widespread parasitic disease caused by
      Echinococcus granulosus. Hydatid cysts are mainly diagnosed in adults except for
      primary cerebral localisation which is electively observed in childhood owing to
      the early manifestation of signs and/or symptoms of the space-occupying mass. In
      July 1995 P.N., a 55-year-old woman, was referred to our attention. She
      complained of intense asthenia, cephalea not responding to NSAIDs and paroxysms
      of tremor. RESULTS: The anamnesis revealed close relationships with dogs since
      infancy and an attack of pleurisy of unknown etiology. The objective examination
      was negative except for an increased volume of the right-hand thyroid lobe.
      Hematochemical tests showed relative eosinophilia, a significant positivity of
      anti-thyroglobulin antibodies and antiperoxidase with normal thyroid function
      indices. Thyroid scan showed a multinodular goitre. Confirmation of eosinophilia
      suggested the performance of a parasitological examination of feces with negative
      results. ECG and EEG were normal. Persistent cephalea led to the performance of
      an encephalic CAT which revealed a cystic formation in the rolandic region,
      subsequently confirmed by encephalic MNR. The positivity of the Ghedini-Weinberg
      test led to the diagnosis of cerebral echinococcosis. Chest X-ray and hepatic
      scan excluded hydatid localisation in these organs. CONCLUSIONS: The case was
      diagnosed as solitary primary cerebral echinococcosis. Medical follow-up was
      commenced with albendazole for six months, after which a control encephalic CAT
      showed the unchanged size of the cysts. The patient consequently underwent
      surgical exeresis.

PMID- 9148232
TI  - [Type 4 renal tubular acidosis caused by spironolactone. A case report].
AB  - The authors describe a case of type 4 renal tubular acidosis, observed in a
      subject with liver cirrhosis, the pathogenetic cause of which was probably the
      assumption of spironolactone. It is thought that, even if such an eventuality is
      not very frequent, it must be considered in clinical practice, in view of the
      negative consequences that the reduction in urinary ammonium excretion and
      hyponatriemia, together with this particular form of acidosis, may have on the
      neurological state of the patients.

PMID- 9148233
TI  - [Non-Hodgkin's lymphoma of the spleen and hepatitis C. Report of a clinical
      case].
AB  - We report a clinical case of a patient affected by splenic non-Hodgkin lymphoma
      and virus C hepatitis. It seems that this kind of association is original because
      as far as we know the association between non-Hodgkin lymphoma and HCV did not
      include non-Hodgkin lymphoma involving the spleen. Indeed, in our patient, there
      was an increase of CD/57 lymphocytes. In our opinion this could be interesting in
      the disorders of the immune system associated with lymphoma.

PMID- 9148234
TI  - Recent Advances in Investigation of Cystic Kidney Disease. Proceedings of a
      conference. Heidelberg, Germany, 27 September 1995.

PMID- 9148235
TI  - Inhibition of nitric oxide synthase induces ultrastructural changes in the
      neurohypophysis of dehydrated rats.
AB  - Neuroglial relation in the rat neurohypophysis have been shown previously to
      change significantly after an acute dehydration stimulus. Here, we demonstrate a
      significant role for nitric oxide as a mediator of this response. Adult male rats
      were injected (i.p.) with 1.5 M NaCl or with 1.5 M NaCl and N omega-nitro-L
      arginine methyl ester (L-NAME) an inhibitor of nitric oxide synthase. Five hours
      after the dehydration stimulus, animals were perfusion fixed and the
      ultrastructure of their neurohypophyses examined. Neurohypophyses of animals
      injected with L-NAME and NaCl had significantly less contact between the basal
      lamina and the membrane of axon terminals than those of animals injected only
      with NaCl. There was also a significantly larger number of axonal profiles
      enclosed within neurohypophysial astrocytes in L-NAME and NaCl injected animals
      than in animals injected only with NaCl.

PMID- 9148236
TI  - Colocalization of acetylcholinesterase and vasoactive intestinal peptide (VIP) in
      nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) positive neurons
      in the intralingual ganglia and perivascular nerve fibers around lingual arteries
      in the porcine, monkey and canine tongue.
AB  - Distribution of nitric oxide synthase in the intrinsic ganglia in the porcine,
      monkey and canine tongue was histologically investigated using the reduced
      nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) method,
      acetylcholinesterase histochemistry and vasoactive intestinal peptide (VIP)
      immunohistochemistry. The majority of intralingual ganglionic cells showed
      intense NADPH-d reactivity with positive acetylcholinesterase reaction or
      positive VIP immunohistochemistry. The NADPH-d positive, acetylcholinesterase
      rich and the NADPH-d positive, VIP immunoreactive nerve fibers are particularly
      conspicuous around intralingual blood vessels. These fibers around the arteries
      in the tongue may be partly derived from the intralingual ganglion cells, because
      some bundles associated with these nerve cells were easily traced on the wall of
      blood vessels. The present study suggests the view that the three markers coexist
      in the axons and nerve terminals of these intralingual neurons.

PMID- 9148237
TI  - Localization of interleukin-1 beta mRNA in the cerebral ganglion of the
      protochordate, Styela plicata.
AB  - There is evidence that interleukin 1 beta (IL-1 beta) plays an important role in
      several biological functions in mammals where it is synthesized by cells of
      haematological, dermal and neural origin. Moreover, production of cytokine-like
      molecules has been demonstrated in some blood cells of non-mammalian vertebrates
      and invertebrates in which also nerve cells are demonstrated to be IL-1 beta
      immunoreactive. The purpose of the present study is to demonstrate the IL-1 beta
      mRNA expression in nerve cells of the ascidian Styela plicata by use of non
      isotopic in situ hybridization technique. The expression of IL-1 beta messenger
      was demonstrated in monopolar neurons in the cortical layer of the cerebral
      ganglion. The neuronal expression of cytokine-like molecules in tunicates
      suggests that IL-1 beta is an ancestral and functionally conserved molecule, and
      that a neuroimmune axis appeared early during the metazoan phylogeny.

PMID- 9148238
TI  - Ultrastructural relationships of the pro-opiomelanocortin axons with the
      serotoninergic neurons in the dorsal raphe nucleus of the rat.
AB  - The relationships of the corticotropin-like intermediate lobe peptide (CLIP)/ACTH
      immunoreactive axons with the serotoninergic and non-serotoninergic neurons in
      the dorsal raphe nucleus of the rat were examined by means of a double label
      immunocytochemical method. It is suggested that the rare contacts established by
      the CLIP/ACTH-immunoreactive fibers with serotoninergic neurons (cell bodies and
      dendrites) are not under a synaptic from. In contrast, the contacts with non
      serotoninergic neurons were predominantly formed with dendrites and showed a
      substantial number of synapses.

PMID- 9148239
TI  - Apamin improves learning in an object recognition task in rats.
AB  - Object recognition was investigated in rats in a two trial unrewarded task. In
      the first trial, two copies of the same object were presented. In the second
      trial, one of the familiar object and a new object were presented. Rats explored
      the new object longer than the familiar object when the intertrial time was 1 h,
      indicating that they remembered the familiar object, but not when the intertrial
      time was 24 h. Rats injected with apamin (a toxin which blocks specifically
      Ca(2+)-activated K(+)-channels) before the first trial spent more time in
      exploring the new object than the familiar object at the second trial, when it
      took place 24 h after the first trial. Injection of apamin just after the first
      trial or before the second trial did not modify the difference in exploration
      time between the new and the familiar object. These results suggest that the
      blockade of Ca(2+)-activated K(+)-channels could improve learning, but not
      consolidation nor restitution of the information, in an object recognition task.

PMID- 9148240
TI  - Amyloid beta protein and transthyretin, sequestrating protein colocalize in
      normal human kidney.
AB  - The localization of amyloid beta protein (A beta), A beta 40, A beta 42, and
      transthyretin (TTR) was investigated immunohistochemically in the autopsied human
      kidney, using polyclonal antibodies against TTR, A beta and C-terminal end
      specific antibodies against A beta 40 and 42. Immunoreactivities of A beta and A
      beta 40 were found both in the proximal and distal tubular epithelial cells. But
      the immunolocalization of A beta 40 was observed predominantly in the distal
      tubules whereas that of A beta 42 was predominantly recognized in the proximal
      tubules. TTR, sequestrating protein for A beta, was present in the proximal
      tubules. The mechanism by which A beta does not form amyloid in Alzheimer's
      disease outside the brain remains unknown. The tubular epithelial cells in the
      kidney may provide a useful system to shed light on this issue.

PMID- 9148241
TI  - Impairment of cortical inhibition in writer's cramp as revealed by changes in
      electromyographic silent period after transcranial magnetic stimulation.
AB  - Changes in silent period (SP) duration following transcranial magnetic
      stimulation (TMS) set at 20% above the motor threshold were studied in six
      subjects suffering from writer's cramp, while performing dystonic movement and
      during voluntary isometric contraction of the muscles mostly involved in the
      dystonic movement. Dependency of SP duration on the intensity of preceding muscle
      contraction was compared on both affected and healthy side. In all subjects SP
      duration during dystonic contraction was shorter than during voluntary
      contraction of the similar strength performed with the same hand. Also, in five
      subjects, SP duration during dystonic contraction was shorter than during
      voluntary contraction of the similar strength performed with the healthy hand. In
      addition, the SP duration on the affected side was negatively associated with the
      intensity of the preceding contraction (i.e. the stronger contraction the shorter
      SP), while on the healthy side it was not the case. It is concluded that central
      inhibitory mechanisms are abnormal in writer's cramp.

PMID- 9148242
TI  - Role of vestibulocerebellar N-methyl-D-aspartate receptors for behavioral
      recovery following unilateral labyrinthectomy in rats.
AB  - The purpose of current study was to elucidate whether vestibulocerebellar N
      methyl-D-aspartate (NMDA) receptors are implicated in MK801 induced vestibular
      decompensation. Sprague-Dawley rats were unilaterally labyrinthectomized (ULX)
      and some of them were uvulonodullectomized before ULX (UNL + ULX). Number of
      spontaneous nystagmus (SN) and degree of head deviation (HD) were used as a
      parameter of behavioral recovery. MK801 treatment 6 h after ULX produced
      significant increases in SN and decreased HD in ULX rats, indicating
      decompensation. In marked contrast, however, MK801 treatment resulted in a great
      reduction of SN and HD in UNL + ULX rats; suggesting involvement of
      vestibulocerebellar NMDA receptors in MK801 induced decompensation during early
      stage of vestibular compensation.

PMID- 9148243
TI  - Effects of repeated methamphetamine administration on dopamine D1 receptor, D2
      receptor and adenylate cyclase type V mRNA levels in the rat striatum.
AB  - Dopamine D1 receptor (D1R), D2 receptor (D2R) and adenylate cyclase type V (AC5)
      mRNAs in the rat dorsal striatum (CPu) and ventral striatum (Acb) were measured
      by in situ hybridization histochemistry (ISHH) after repeated methamphetamine
      (MAP) administration. MAP (4 mg/kg) or an equivalent volume of saline was
      administered intraperitoneally once daily for 10 days to male Wistar rats. After
      7 days of abstinence, behavioral experiment with MAP-challenge revealed that a
      significant behavioral sensitization was achieved in MAP-treated animals. The
      animals were sacrificed 7 days after the last injection and brain sections were
      analyzed by ISHH using 35S-labeled antisense oligonucleotide probes. We found
      that D1R mRNA levels in the CPu were significantly increased (124% of control, P
      < 0.01). In contrast, repeated MAP-treatment did not significantly affect the
      expression of D1R mRNA in Acb or mRNA for D2R or AC5. It was concluded that MAP
      induced behavioral sensitization is accompanied by increased D1R mRNA levels in
      CPu.

PMID- 9148244
TI  - Parallel increases in [alpha-125I]bungarotoxin binding and alpha 7 nicotinic
      subunit immunoreactivity during the development of rat hippocampal neurons in
      culture.
AB  - Previous studies have shown that hippocampal neurons cultured at high density
      express alpha-bungarotoxin binding sites and have alpha 7 nicotinic acetylcholine
      receptor subunit immunoreactivity [Barrantes, G.E., Rogers, A.T., Lindstrom, J.
      and Wonnacott, S., Brain Res., 672 (1995) 228-236]. We now examine both of these
      parameters in well-characterized hippocampal neurons cultured at sufficiently low
      densities to resolve individual neurons and their processes. The specific binding
      of [alpha-125I]bungarotoxin is first detectable after 3 days in culture and
      increases during the next 12 days in culture, reaching a maximum of approximately
      30,000 binding sites per cell. This is accompanied, over the same timecourse, by
      an increase in immunoreactivity for two antibodies that specifically bind to the
      alpha 7 subunit. Both cell bodies and processes were labelled by 9 days in
      culture. The timecourse of alpha 7-type nicotinic receptor expression resembles
      that previously described for synapse formation in hippocampal cultures.

PMID- 9148245
TI  - Similar deficits of central histaminergic system in patients with Down syndrome
      and Alzheimer disease.
AB  - In order to study whether Alzheimer-like neuropathological changes involve the
      central histaminergic system we measured the concentration of histamine, its
      precursor histidine as well as the activity of histidine decarboxylase (HDC) and
      histamine-N-methyl-transferase (HMT) in frontal cortex of aging Down syndrome
      (DS) patients, Alzheimer patients and control individuals. The study populations
      were also investigated for choline acetyltransferase (ChAT) activity, since
      reduced ChAT activity is an established biochemical hallmark in DS and Alzheimer
      disease (AD). HDC and ChAT activity were reduced in brains of both DS and
      Alzheimer patients versus control patients. Additionally, we observed a
      significant decrease of histamine levels in the DS group. Histamine levels in AD
      brains tended to be decreased. Histidine concentrations and HMT activities were
      comparable between the three groups. Thus, our results for the first time show
      histaminergic deficits in brains of patients with DS resembling the neurochemical
      pattern in AD. Neuropathological changes may be responsible for similar
      neurochemical alterations of the histaminergic system in both dementing
      disorders.

PMID- 9148247
TI  - alpha-Lipoic acid corrects neuropeptide deficits in diabetic rats via induction
      of trophic support.
AB  - This study compared the effects of treatment of diabetic rats with either alpha
      lipoic acid (100 mg/kg/day i.p. 5 days/week) or with recombinant human nerve
      growth factor (rhNGF; 0.2 mg/kg s.c. 3 days/week) on NGF-like immunoreactivity
      (NGFLI) and neuropeptide Y-like immunoreactivity (NPYLI) levels in the sciatic
      nerve and on the release of substance P-like immunoreactivity (SPLI) from the
      spinal cord in response to electrical stimulation of the dorsal roots in vitro.
      Diabetic rats showed depletion of NGFLI and NPYLI, together with reduced release
      of SPLI. Treatment with NGF increased the sciatic nerve NGFLI (to four times that
      seen in untreated diabetic rats) and normalised stimulus-evoked release of SPLI,
      but did not affect the sciatic nerve NPYLI. Treatment with alpha-lipoic acid
      caused a small non-significant increase in sciatic nerve NGFLI, but normalised
      both NPYLI levels and stimulus-evoked release of SPLI. These findings indicate
      that alpha-lipoic acid can boost neurotrophic support in diabetic rats, with
      effects beyond those related to NGF.

PMID- 9148246
TI  - Genetic association studies between dementia of the Alzheimer's type and three
      receptors for apolipoprotein E in a Caucasian population.
AB  - The epsilon 4 allele of the apolipoprotein E gene (ApoE) is associated with an
      increased risk for sporadic and some familial forms of Alzheimer's disease (AD)
      but the precise mechanism of pathogenesis is unknown. ApoE is a ligand for at
      least three receptors in the central nervous system, low density lipoprotein
      receptor (LDL-R), very low density lipoprotein receptor VLDL-R and low density
      lipoprotein-like receptor (LRP). We have tested for association between these
      receptors and dementia of the Alzheimer's type (DAT) in a clinically based sample
      of Caucasian cases and age-matched controls. In contrast to findings in a
      Japanese cohort we detected no association between DAT and a polymorphism in the
      VLDL-R gene. No association was detected with the LDL-R gene. We observed a
      possible association between the 87 allele of a polymorphism within the LRP gene
      and DAT which remained significant after correction for multiple testing. When
      the effects of known risk factors for AD such as ApoE epsilon 4 were applied, the
      effect of LRP no longer reached conventional levels of statistical significance.
      Nevertheless, LRP is a plausible candidate gene and we may be observing a minor
      risk factor that will require further examination in other large independent
      samples to assess whether it truly modifies susceptibility to DAT.

PMID- 9148248
TI  - Ultrastructural evidence for a direct pathway from the pontine micturition center
      to the parasympathetic preganglionic motoneurons of the bladder of the cat.
AB  - Light microscopy tracing studies have provided evidence that the pontine
      micturition center (PMC) projects to the area of the intermediolateral cell
      column of the sacral spinal cord. Although this region contains parasympathetic
      preganglionic motoneurons of the bladder and colon, it also contains many local
      interneurons and neurons projecting to supraspinal levels. The present study
      demonstrates that neurons in the PMC indeed project to preganglionic bladder
      motoneurons. Wheat germ agglutinin horseradish peroxidase was injected in the PMC
      and cholera toxin B subunit was injected in the bladder wall. Many anterogradely
      labeled fibers from the PMC were found to terminate on somata and dendrites of
      the retrogradely labeled preganglionic bladder motoneurons. The terminals were
      filled with many round vesicles and possessed an asymmetric synaptic cleft,
      suggesting an excitatory function.

PMID- 9148249
TI  - Pattern of synaptophysin immunoreactivity in the efferent nerve terminals of the
      guinea pig cochlea.
AB  - The goal of the present study was to analyze the distribution of efferent 8th
      nerve synaptic endings in a surface preparation of the guinea pig cochlea using
      synaptophysin antibodies. Employing light and confocal microscopy synaptophysin
      immunoreactivity was found exclusively at the base of the outer hair cells (OHCs)
      and the inner hair cells (IHCs) axosomatic efferent synapses. Qualitative and
      quantitative differences were found between the OHCs and the IHCs
      immunoreactivity. Efferent nerve endings innervating IHCs were comparatively
      smaller, more numerous and densely packed. Efferent terminals demonstrated a
      longitudinal gradient for the IHCs and a longitudinal and radial gradient for the
      OHCs. Quantitative analysis of synaptophysin immunofluorescence demonstrated a
      higher percentage of efferent terminals innervating the IHCs and the OHCs in the
      mid and basal segments of the cochlea than in the apical regions. In addition, a
      radial gradient from the 1st to 3rd row of OHCs was evident. The results from the
      present study show that the analysis of synaptophysin immunoreactivity on
      cochlear surface preparations allows the efferent innervation to be determined
      throughout the entire cochlea. This technique allows for a rapid assessment of
      the normal cochlea as well as after cochlear insult.

PMID- 9148250
TI  - Spatial responses to light in mice with severe retinal degeneration.
AB  - It is known that mice homozygous for the retinal degeneration (rd) mutation are
      able to synchronize their circadian rhythms to light-dark cycles. In the present
      experiments mice were given a choice of a dark or an illuminated living and
      nesting area. C3H, CBA and C57 rd/rd mice spent more time in the dark than in the
      illuminated area. Also, they spent as much time in the dark area as did wildtype
      controls. This shows that, despite advanced retinal degeneration, light can be
      used to control behaviour in space as well as in time. This was true of mutant
      mice over a year old, when retinal degeneration is very severe, and also of a
      transgenic strain of mice whose rods are destroyed as they begin to develop in
      the first few weeks after birth.

PMID- 9148251
TI  - Neuronal injury in experimental status epilepticus in the rat: role of hypoxia.
AB  - While it seems axiomatic that hypoxia is a risk factor for neuronal death during
      prolonged seizures, the classic neuropathologic literature does not confirm such
      an association. We investigated this issue by inducing status epilepticus in
      normoxic (PaO2 approximately 100 mmHg) and hypoxia (PaO2 approximately 50 mmHg)
      rats, using heat-shock protein (HSP) expression as an index of early cell injury
      and acid fuchsin staining to detect cell death. Neither stress protein induction
      nor neuronal death was increased in the selectively vulnerable CA3c region of
      hippocampus, or in cerebral cortex, of hypoxic compared to normoxic animals.
      These data support the concept that moderate hypoxia is not a risk factor for
      brain injury from status epilepticus.

PMID- 9148252
TI  - Human hair follicles as a peripheral source of tyrosine hydroxylase and aromatic
      L-amino acid decarboxylase mRNA.
AB  - Total RNA from human hair follicles was reverse transcribed and amplified using
      primers specific for aromatic L-amino acid decarboxylase (AADC) and tyrosine
      hydroxylase (TH). Agarose electrophoresis of the amplified products showed
      reverse transcription polymerase chain reaction (RT-PCR) products of the expected
      size for both TH and AADC. Sequencing showed that the amplified products matched
      the known sequences of TH and AADC. This study identifies hair follicles as a
      convenient, uninvasive, source of the mRNA for TH and AADC. Analysis of these
      mRNA's may be useful in the diagnosis and investigation of conditions resulting
      from qualitative changes in the genes that code for these enzymes.

PMID- 9148254
TI  - Vitreal alterations in retinitis pigmentosa: biomicroscopic appearance and
      statistical evaluation.
AB  - The authors present a biomicroscopic evaluation of vitreal alterations in a large
      group of patients affected by primary retinitis pigmentosa (RP). 286 RP patients
      (571 eyes), 153 (305 eyes) males and 133 (266 eyes) females, have been studied;
      the mean age of this whole group was 37.26 + or - 14.93 years (age range: 5-77).
      Vitreal static and dynamic biomicroscopy was performed on fully dilated pupils by
      means of a Haag-Streit 900 slit-lamp and high-power positive precorneal lenses
      (+90 and +78 dpt Volk lenses). Most patients showed floating cottonball-like
      condensations (26.824%) often associated with fibrillary degeneration (15.88%),
      while non-pigmentary vitreal particulation was detected in 26.609% of cases and
      the pigmentary type in 12.017%, respectively. Posterior vitreal detachment was
      detected alone in only 0.43% of cases while 18.24% of examined eyes showed no
      vitreal alterations. A high statistical correlation between vitreal aspects and
      pigmentary grading of the fundus oculi (p = 0.0001), as well as duration of the
      disease (p = 0.0074), was found; at the same time, no statistical correlation
      with refractive error was demonstrated (p = 0.47).

PMID- 9148253
TI  - Efficacy of a novel hydrogel formulation in human volunteers.
AB  - In a two-period crossover study, 20 subjects without an ocular disease received
      single doses of either a novel timolol hydrogel (T-Gel 0.1%) or aqueous timolol
      0.5% in one eye and placebo in the fellow eye. Diurnal variation curves of
      intraocular pressure of both eyes were obtained for a 24-hour period. Peak
      effects up to -30% of the baseline were observed. A statistically significant
      residual effect was still detectable 24 h after application. The timolol gel had
      the same efficacy in lowering intraocular pressure as the commercially available
      aqueous timolol solution with a five times higher strength. Equivalence of
      treatment effects was statistically proved.

PMID- 9148255
TI  - Picture resembling hemicentral retinal vein occlusion in the acquired
      immunodeficiency syndrome: is it related to cytomegalovirus?
AB  - Three HIV-seropositive subjects presented with diffuse inferior retinal
      hemorrhages. The first patient had an inferior hemicentral vein occlusion with
      subsequent development of an inferior cytomegalovirus retinitis. Two other
      patients had an inferior 'hemorrhagic' cytomegalovirus retinitis mimicking a
      venous occlusion, with the retinitis being subtle in 1 patient. We speculate
      that: (1) venous occlusion may predispose to cytomegalovirus infection of the
      retina by stasis and ischemic loss of endothelium; (2) early cytomegalovirus
      infection of the large retinal veins may give the picture of a hemorrhagic
      retinopathy in a subset of patients with cytomegalovirus retinitis. The
      differential diagnoses of hemorrhagic retinopathy in HIV-seropositive subjects
      include: cytomegalovirus retinitis, retinal vein occlusion, syphilitic retinitis
      and retinopathy of severe anemia.

PMID- 9148256
TI  - Clinical and immunogenetic investigation of a Laotian patient with Vogt-Koyanagi
      Harada's disease.
AB  - Vogt-Koyanagi-Harada's (VKH) disease has been known to be associated with HLA
      class II antigen, HLA-DR4 and -DR53. Recent recombinant DNA technical advances
      have allowed us to investigate the genetic polymorphism of HLA antigens at the
      molecular level. By use of the polymerase chain reaction restriction fragment
      length polymorphism (PCR-RFLP) technique we have found that VKH disease is
      closely associated with HLA-DRB1*04 (DRB1*0405/ DRB1*0410) and DQB1*04
      (DQB1*0401/DQB1*0402) in the Japanese. Here, we will describe a typical case of a
      Laotian patient with VKH disease and the results of HLA typing: the patient
      showed a conservation of one of the major haplotypes observed in Japanese VKH
      patients, DRB1*0405-DQB1*0402.

PMID- 9148257
TI  - Subretinal fibrovascular proliferation in retinal arteritis with multiple
      aneurysmal dilatations: a case report.
AB  - A 14-year-old boy with bilateral retinal arteritis with multiple aneurysmal
      dilatations complicated by secondary macular subretinal fibrovascular
      proliferation and epimacular membrane formation is described. This complication
      has not been previously reported in this rare disorder. Systemic steroid and
      immunosuppressive therapy did not change the course of the disease. Improvement
      of macular edema and subretinal exudation was achieved following pars plana
      vitrectomy, posterior hyaloid dissection and epiretinal membrane removal.

PMID- 9148258
TI  - Anterior ischemic optic neuropathy in a patient with positive antinuclear
      antibody and lupus anticoagulant findings.
AB  - A 64-year-old woman complained of blurred vision in her right eye. A pale optic
      disc with a blurred nasal margin was found in the right fundus. An inferior
      altitudinal defect in the right eye was observed on Goldmann perimetry. Her right
      visual acuity deteriorated to 0.1. Her antinuclear antibody and lupus
      anticoagulant test results were positive. Intravenous methylprednisolone (1,000
      mg/day) improved her right visual acuity to 1.0. We believe that the anterior
      ischemic optic neuropathy in our patient may be associated with the presence of
      positive antinuclear antibody and lupus anticoagulant findings.

PMID- 9148259
TI  - Long-term elevation of intraocular pressure after neodymium: YAG laser posterior
      capsulotomy.
AB  - Uncomplicated extracapsular cataract extraction (EC) followed by posterior
      chamber lens implantation (PCL) has been shown to cause long-term lowering of
      intraocular pressure (IOP) in most patients. Since it has been suggested that
      Neodymium: YAG (Nd:YAG) laser capsulotomy can provoke persistent glaucoma, we
      examined the hypothesis that Nd:YAG laser capsulotomy may lead to a permanent
      elevation of IOP. In a case-control study, we compared two groups of 75
      normotensive patients, who were unilaterally pseudophakic after
      phacoemulsification (PE) + PCL. Patients in group 1 had undergone Nd:YAG
      capsulotomy at least 2 months prior to this study, while in group 2 the posterior
      capsule was intact. Both groups were selected at random. Prior to surgery, none
      of the patients had suffered from glaucoma. Goldmann applanation tonometry was
      performed in both eyes of each patient and from that the ratio of
      IOP(pseudophakic)/IOP(phakic) was calculated. The distribution of this ratio for
      the two groups was compared using the Wilcoxon signed-rank test. There were 52
      female and 23 male patients in group 1 versus 56 female and 19 male patients in
      group 2. Their mean ages were 75 + or -11 (group 1) and 75 + or - 9 years (group
      2). The mean interval after PE + PCL was 48 + or - 29 months for patients with
      Nd:YAG capsulotomy and 16 + or - 17 months for patients with intact posterior
      capsule. Since the Nd:YAG capsulotomy, 28 + or - 23 months had elapsed on
      average. The median ratio of IOP (pseudophakic)/IOP(phakic) was higher in the
      Nd:YAG capsulotomy group than in the group of patients with an intact posterior
      capsule (1.00 vs. 0.80; p < 0.0001). There was almost no percentile, for which
      the distribution curve of group 1 intersected the curve of group 2. The median
      IOP in pseudophakic eyes was 14 mm Hg in group 1 and 12 mm Hg in group 2
      (p<0.0001). These results are in accordance with the hypothesis that Nd:YAG
      capsulotomy will raise IOP permanently in most patients. Therefore Nd:YAG
      capsulotomy may harbor the risk of glaucomatous optic nerve damage in the long
      run. Long-term follow-up seems advisable in order to prevent possible glaucoma
      damage.

PMID- 9148261
TI  - Strabismus surgery in ocular myasthenia gravis.
AB  - We evaluated the efficacy of eye muscle surgery in 4 patients with ocular
      myasthenia gravis with troublesome diplopia. All patients were in remission and
      had shown a consistently stable angle of deviation for at least 6 months
      preoperatively. The extent of eye muscle surgery was based on the degree of
      deviation in the primary position, and conventional recession and resection
      procedures were performed in 3 patients and hang-loose recession with an
      adjustable recession in 1. Single binocular vision was obtained in 3 patients in
      the primary position without prism correction or compensatory head posture.
      Electron-microscopic studies on the eye muscle specimens obtained at strabismus
      surgery revealed non-specific degenerative findings for the muscle fibers and
      sarcomeric disorganization compared to that in a control extraocular muscle.

PMID- 9148260
TI  - Laser photocoagulation around the foci of toxoplasma retinochoroiditis: a
      descriptive statistical analysis of 35 patients with long-term follow-up.
AB  - Thirty-five patients with toxoplasma retinochoroiditis, receiving medical
      treatment and then treated with laser photocoagulation around the foci, were
      retrospectively evaluated for the risk of recurrence of the retinochoroiditis
      with a Kaplan-Meier representation. The recurrence rates with 95% symmetric
      confidence intervals were: at 1 year, 12.7 + or - 13%, at 2 years, 19.8 + or -
      15%; at 3 years, 24.0 + or - 16%; at 4 years, 33.3 + or - 19%; at 5,6 and 7
      years, 53.5 + or - 21%; at 8 and 9 years 66. 8 + or - 22%. With the data provided
      by our series, it is not possible to show the efficacy of laser photocoagulation
      as a prevention of recurrence in toxoplasma retinochoroiditis. Moreover, because
      of their heterogeneity, the recurrence rates from the literature cannot provide
      precise data for a comparison. Concerning the laser-induced thermal damage, the
      potential therapeutic mechanism of the laser procedure is discussed.

PMID- 9148262
TI  - Clinical evaluation of a topographically based contact lens fitting software.
AB  - BACKGROUND: Second generation corneal topography-based contact lens software
      programs attempt to fit the cornea based on topographical information rather than
      simulated keratometry and nomogram-based fits. The EyeSys System 2000 Pro-Fit
      software (Version 3.1) was clinically evaluated for efficiency in fitting rigid
      gas permeable (RGP) lenses on 22 normal subjects. METHODS: Balanced manifest
      refractions, slitlamp examinations, keratometry, computerized topographic
      analysis and lens fitting, and manual diagnostic RGP fitting were performed on
      all patients. The topographically fit eyes were compared to corresponding eyes
      which were manually fit with diagnostic trial lenses. Lens parameters for the
      topographically fit eye were chosen after an optimal fluorescein pattern was
      achieved by either accepting the initially recommended Pro-Fit lens or a
      modification. Final lens parameters were based on clinical performance. Lenses
      were reordered when there was a need for base curve changes of 0.1 mm or more,
      power alterations of +/- 0.50 D or more, or for any alteration in diameter, optic
      zone, or edge lift. RESULTS: Both manual and topographically fit groups achieved
      17/22 (77%) eyes successfully fit without any subsequent lens modifications. Time
      records for the manually fit group averaged 16.5 min, whereas the topographically
      fit group averaged 8.0 min. CONCLUSIONS: This study reports a 51.4% reduction in
      chair time when using a topographically based contact lens software program while
      achieving the same clinical results as in traditional diagnostic RGP fitting,
      suggesting increased efficiency in fitting RGPs to normal eyes.

PMID- 9148263
TI  - Hard contact lenses alter accommodative gain but do not prevent refractive
      adaptation in chicks.
AB  - This study compared the compensatory response to hyperopic defocus imposed on
      chicks in two different ways: (1) with-10 D spectacle lenses, and (2) with plano
      hard contact lens. The hyperopia seen with the contact lenses in situ was a
      consequence of their flat profile relative to the chick cornea, resulting in a
      negative fluid lens of approximately 16 D at day 2 and 9 D by day 10. This
      decrease with age reflects the corneal flattening that accompanies normal eye
      growth. By optically neutralizing the cornea, the contact lenses also had two
      other important effects: (1) a reduction in refractive astigmatism to almost
      negligible levels, and (2) a reduction in accommodative gain. The latter effect
      reflects the loss of the corneal component of the chick's accommodation and was
      estimated to be of the order of 40 to 57%, based on measurements made using
      topically applied nicotine to stimulate accommodation. Thus any estimate of the
      imposed hyperopic defocus based on accommodative effort required to overcome such
      errors will be too large. Chicks wearing either lens type on a continuous basis
      from hatching to 10 days only partially compensated for the imposed hyperopia
      through an increase in vitreous chamber growth. However, the effects were smaller
      in the spectacle lens group (e.g., a mean myopic shift of -4.1 +/- 2.3 D compared
      to -6.3 +/- 2.4 D for the contact lens group at day 10), although both groups
      experienced similar amounts of hyperopic defocus around day 10 (effective power
      of -10 D spectacle lens: -9.4 D). The changes seen in the spectacle lens group
      thus represent poorer compensation, i.e., 44 vs. 71% of the imposed error.
      However, overcompensation is the predicted effect, if any, of the accommodative
      deficit imposed on the contact lens group, and this was not seen. That
      compensation, albeit incomplete, occurred with the contact lens as well as the
      spectacle lens, suggests that neither accommodation nor astigmatism are
      fundamental cues for emmetropization as modeled here.

PMID- 9148264
TI  - Visual anomalies in young children exposed to cocaine.
AB  - PURPOSE: The number of children exposed to cocaine in utero each year is
      increasing. Recent reports suggest significant visual anomalies in infants
      prenatally exposed to cocaine. The purpose of this retrospective study was to
      determine if children exposed prenatally to cocaine were at a greater risk for
      visual abnormalities, such as strabismus and significant refractive errors.
      METHODS: This pilot study was conducted at two sites, an outpatient clinic and a
      hospital-based practice. Consecutive files from January to July, 1993, of 79
      children (aged 4 months to 94 months); who were identified by case history or
      meconium analysis information as being exposed to cocaine in utero, were
      reviewed. Fifty-five children met the inclusion criteria for the study. In
      addition, a control group of 100 pediatric patients were randomly selected from
      the pediatric patients seen at the outpatient clinical site. RESULTS: Of the 30
      children from the Illinois Eye Institute (IEI) and the 25 children from The
      Children's Hospital (TCH), spherical refractive errors in the right eye ranged
      from +6.50 to -12.50 D. The median refractive errors were +0.75 and +0.50 D,
      respectively. No statistical difference was found in spherical refractive error,
      astigmatism, or anisometropia between the cocaine-exposed cohorts and the control
      group (N = 100). Strabismus was found in 15/55 (27%) of the children in the
      cocaine-exposed group. There was a statistically significant difference in the
      prevalence of strabismus between the cocaine-exposed group and the control group.
      Further analysis revealed that full birthweight (> 2500 g) children prenatally
      exposed to cocaine were at a greater risk for strabismus as compared to the full
      birthweight control group. Ocular abnormalities were rare, but included optic
      nerve atrophy and retinopathy of prematurity. CONCLUSIONS: These data suggest
      cocaine exposure during pregnancy may place a child at risk for conditions that
      may negatively impact the visual system, specifically strabismus.

PMID- 9148265
TI  - The relation of clinical saccadic eye movement testing to reading in
      kindergartners and first graders.
AB  - Although a substantial body of research has demonstrated an association between
      reading and eye movements, this association has not been examined in
      kindergartners. Therefore, the relation between psychometric eye movement scores
      and reading skill was studied in a masked investigation with 181 kindergartners
      and first graders (mean age 6.25 years) from a middle class, suburban, elementary
      school near Cleveland, Ohio. Eye movements were evaluated with the New York State
      Optometric Association King-Devick (NYSOA K-D; Bernell Corporation, South Bend,
      IN) and the Developmental Eye Movement tests (DEM; Bernell Corporation, South
      Bend, IN). Digit knowledge was assessed with Reversals Frequency Test Execution
      subtest (Gardner). Reading performance was measured with Metropolitan Achievement
      Test 6 (MAT6) Reading Test and teachers' assessments. The number of unknown or
      reversed numbers on Gardner was significantly related to test times on the NYSOA
      K-D and DEM, but not the DEM ratio. Outcome on NYSOA K-D, determined by errors in
      conjunction with test time, was significantly related to reading ability in 5
      year-olds (p = 0.0129), 6-year-olds (p = 0.0167), and the entire subject group
      when controlling for age (p = 0.0008). Our findings suggest that: (1) DEM factors
      out automaticity of number knowledge; (2) the NYSOA K-D can be completed by
      kindergartners; (3) the DEM is too difficult for many kindergarteners; and (4)
      performance on the NYSOA K-D is related to reading performance in 5- and 6-year
      olds in kindergarten.

PMID- 9148266
TI  - Comparison of the monocular occlusion and a direct method for objective
      measurement of fixation disparity.
AB  - PURPOSE: Previous studies have measured objective fixation disparity using a
      monocular occlusion method, by which the monocular components of misalignment are
      revealed by measuring the shift in the position of the fixating eye after
      occlusion of the other eye. METHODS: We assessed the use of the monocular
      occlusion method by comparing it to direct measurements of binocular vergence.
      RESULTS: The direct method required precise calibration, but was found to be
      reliable. Several problems were discovered with the monocular occlusion method:
      (1) when using a central fusion stimulus, fixation was difficult to control
      accurately enough to measure the small monocular shifts in eye position expected
      at lower vergence demands; (2) with a peripheral fusion target, objective
      fixation disparity could not be measured directly; and (3) upon occlusion, a
      variable saccade occurred in the fixating eye. CONCLUSION: Objective measurement
      of fixation disparity with the direct method is quicker and more reliable than
      with the monocular occlusion method.

PMID- 9148267
TI  - Comparison of the performance of the Nidek NT-2000 noncontact tonometer with the
      Keeler Pulsair 2000 and the Goldmann applanation tonometer.
AB  - We compared the performance of a new noncontact tonometer (NCT), Nidek NT-2000,
      with the Keeler Pulsair 2000 and the Goldmann applanation tonometer (AT). Twenty
      two subjects with intraocular pressure (IOP) ranging from 10 to 21 mmHg were
      recruited and their IOP measured using each technique on 2 different days. The NT
      2000 produces repeatable IOP readings and is comparable to the Goldmann AT. There
      is a significant between-visits difference in IOP when using the Pulsair 2000.
      The reproducibility of IOP measurements made with the Pulsair 2000 is relatively
      poor when compared to the Goldmann AT and the NT-2000. IOP measurements made with
      the Goldmann AT show good repeatability and reproducibility when the mean of
      three IOP readings are used. When a single Goldmann reading is used variability
      is increased. There is no significant difference in the IOP readings made on the
      first visit between techniques.

PMID- 9148268
TI  - A computer-interfaced vertometer system for contact lenses.
AB  - BACKGROUND: The conventional vertometer (lensometer) is difficult to use for
      accurate measurement of contact lenses whose back vertex power (BVP) varies
      across the optic zone. BVPs of multifocal rigid and soft contact lenses have
      previously been measured using a conventional vertometer incorporating the
      Scheiner principle, which makes use of two light paths equidistant from the
      center of the lens. METHODS: We have developed a computer-based vertometer system
      based on the Scheiner principle which can be used to produce a profile of BVPs
      across rigid and soft contact lenses. A computer interface to the vertometer
      allows rapid acquisition of readings and software-based ray tracing derives in
      air dioptric power readings across the optic zone at specific ray heights.
      RESULTS: Results are presented for soft and rigid, and spherical and aspheric
      surface contact lenses. CONCLUSIONS: The system improves the measurement
      resolution of a standard vertometer and shows an acceptable level of precision
      and accuracy for most applications.

PMID- 9148269
TI  - Importance of the lipid layer in human tear film stability and evaporation.
AB  - PURPOSE: Previous work on rabbits has demonstrated a four-fold increase in tear
      evaporation when the tear lipid layer is removed. However, in vitro work has
      suggested that the lipid layer does not play a role in retarding evaporation of
      the aqueous layer. The importance of the lipid layer in human tear film stability
      and evaporation was determined in the current study by measurement of these
      parameters in the same individuals. METHODS: The left eyes of 161 normal and dry
      eye subjects (72 males, 89 females), with an age range of 13 to 85 years, were
      examined. Tear evaporation was derived from the vapor pressure gradient measured
      with a modified Servomed evaporimeter. Lipid layer structure and noninvasive
      break-up time (NIBUT) were assessed clinically, by specular reflection, with the
      Keeler Tearscope. Lipid layer structure was categorized into marmoreal (open and
      closed meshwork), flow, amorphous, and colored fringe (normal and abnormal)
      patterns. These observed patterns reflect lipid layer thickness. Ambient
      temperature and relative humidity remained fairly constant throughout the
      experiment. RESULTS: Tear evaporation rate was found to vary significantly with
      different lipid layer patterns. Eyes with no visible lipid layer, or exhibiting
      an abnormal colored fringe pattern (with clumping of lipid amidst areas of little
      or no lipid cover), demonstrated a significantly higher rate of evaporation of
      the tear film (p < 0.001). There were no significant differences amongst the
      remainder of the patterns. The NIBUT was also found to vary significantly with
      lipid layer pattern (p < 0.001), with the absent or abnormal colored fringe lipid
      patterns exhibiting the poorest stability. CONCLUSIONS: Where the human lipid
      layer is absent, or is not confluent, and the tear film is unstable, tear
      evaporation is increased four-fold. However, where there is a stable, intact
      lipid layer, regardless of lipid thickness, tear evaporation is retarded.

PMID- 9148270
TI  - [Clinical significance of nuclear medicine in the presurgical diagnosis of
      epilepsy].

PMID- 9148271
TI  - [123I-alpha-methyltyrosine scintigraphy in malignant melanoma].
AB  - AIM: The aim of the study was to evaluate the ranking of the scintigraphy with L
      3-123I-alpha-methyltyrosine (123I-AMT) in metastasized melanoma. METHODS: 26
      metastases and one primary tumor of a malignant melanoma in six patients were
      examined with 123I-AMT whole-body scintigraphy and SPECT. Positron Emission
      Tomography with 2-18F-fluoro-2-desoxy-D-glucose (18F-FDG) was used as the golden
      standard. RESULTS: With 123I-AMT-SPECT 8/10 metastases in the thorax > 1.6 cm
      were detected (ratio T/NT 1.2-1.8), metastases < 1.6 cm were not detectable with
      SPECT. In 123I-AMT whole-body scintigraphy not one lesion showed a positive tumor
      uptake. CONCLUSION: In single cases 123I-AMT scintigraphy can be helpful in
      staging of malignant melanoma.

PMID- 9148273
TI  - Clinical significance of nuclear medicine emergency studies. 9th Nuclear Medicine
      Workshop Innsbruck - Hannover 1996.

PMID- 9148272
TI  - [Influence on extratumoral organ activities of tumor-affinity samarium-153
      preparations].
AB  - AIM: Possibilities to exercise an influence on the biodistribution of a tumor
      affine 153Sm-preparation, samarium-153-nitrilotriacetate (NTA), were tested.
      METHODS: Animals experiments on tumor-bearing mice after additional application
      of EDTMP (ethylenediamine tetramethylene phosphonate) for the reduction of
      extratumorale liver-radioactivity and yttrium chloride for the reduction of
      unwanted underground radioactivity in bone were carried out. Furthermore, the
      combination of both measurements was tested. RESULTS: The biodistribution of
      153Sm-NTA showed a rather low tumor-radioactivity of app. 0.72%/g. The additional
      EDTMP-application caused a dose-dependent decrease of the underground
      radioactivity in liver especially if given 2 h in advance or simultaneously. The
      additional application of the stable yttrium salt reduced the bone radioactivity
      on simultaneous increase of liver- and spleen-radioactivity and practically
      unchanged tumor-radioactivity. The combined use of EDTMP together with the bone
      affine metal salt led to a reduction of liver radioactivity on simultaneous
      reduction of bone radioactivity. CONCLUSIONS: The background radioactivity can be
      reduced on unchanged tumor-radioactivity by combined Na-EDTMP/YCl3-application.
      The present results do not allow a therapeutic exploitation because of the low
      tumor accumulation.

PMID- 9148274
TI  - [A method for combined scatter and attenuation correction without transmission
      measurement for myocardial SPECT with 99m-Tc binding].
AB  - AIM: A new strategy is introduced for a double-head gamma-camera to calculate and
      to correct for attenuation distribution from count rates of backscattered
      radiation of 99mTc in the human thorax/myocardium setting. The intention was to
      gain segmented and calibrated images of distribution employing the structures of
      lungs and other tissues, so that attenuation may be subsequently corrected by the
      method of Chang METHODS: Acquisition was done simultaneously in three energy
      window for 99mTc to receive both emitted and scattered radiation. The acquire
      projections were used to calculate the attenuation distribution and to execute a
      scatter correction by the method of Ogawa et. al. By measuring phantoms and
      evaluating a set of patient studies, quality for both of the approaches towards
      attenuated distribution and the quality of attenuation correction was tested and
      an optimal setting for parameters involved was selected. RESULTS: The procedure
      adequately approaches the correction for both emitted and scattered radiation in
      SPECT, as experienced in phantom and patient studies. Clinical usefulness was
      preliminary documented in selected cases. In normal perfusion, distribution was
      more homogeneous. Perfusion defects appeared more definitive. Problems occurred
      in high adjacent non-target activity (e.g., in the gallbladder) and with low
      count rate statistics. CONCLUSION: Myocardial 99mTc MIBI SPECT may be effectively
      corrected for both attenuation a scatter without an additional transmission
      device.

PMID- 9148275
TI  - [Importance of iterative reconstruction ISA in the diagnosis of liver
      hemangioma].
AB  - AIM: To evaluate whether the iterative reconstruction methodology ISA is superior
      to the standard technique of filtered back-projection. METHODS: In a
      retrospective study, we evaluated images of 39 patients with solitary or multiple
      liver tumors who underwent blood pool imaging in SPECT technique in order to
      prove or exclude the presence of hemangioma. RESULTS: Activity accumulations in
      accordance with the diagnosis of liver hemangioma could be visualized in 34 cases
      by the iterative, in 31 cases by the filtered back-projection methodology. As
      compared to filtered back-projection, the iteratively reconstructed lesions
      showed higher tumor-to-background ratios and were more easily distinguished from
      structures in their neighborhood. Furthermore, the iterative methodology resulted
      in a more homogeneous activity distribution in the liver, whereas the
      inhomogeneous "patchy" structure of the liver parenchyma in filtered back
      projection provokes difficulties in the distinction from reconstruction
      artifacts. A clearer visualization of vessels and a better distinction between
      the right kidney and the liver was possible by the iterative algorithm, leading
      to advantages in the recognition of centrally or dorsally located lesions in the
      right hepatic lobe. CONCLUSION: These data indicate that the use of our iterative
      algorithm in performing liver blood pool imaging yields a higher sensitivity and
      a better diagnostic accuracy in diagnosing liver hemangioma.

PMID- 9148276
TI  - Effects of aluminium on the mineral metabolism of rats in relation to age.
AB  - The present study was conducted to assess in rats the effects of chronic
      aluminium (Al) exposure on calcium (Ca), magnesium (Mg), manganese (Mn), copper
      (Cu), zinc (Zn) and iron (Fe) accumulation and urinary excretion in relation to
      the age of the animals. Male young (21 day old), adult (8 months), and old (16
      months) rats were orally exposed to 0, 50, or 100 mg Al/kg/day for a period of
      6.5 months. Urinary levels of essential elements were determined after 3 and 6.5
      months of exposure, whereas tissue Ca, Mg, Mn, Cu, Zn and Fe concentrations were
      examined after 6.5 months of Al administration. A number of age-related changes
      in tissue accumulation and urinary excretion of essential elements following
      chronic exposure to Al were found. Concentrations of essential elements in most
      tissues of young Al-exposed rats were generally lower than those of adult and old
      rats. The highest levels of essential elements were found in old animals. Liver,
      testes and spleen were the tissues that showed the most remarkable increases in
      relation to the levels found in those tissues of young rats. Adult rats showed a
      pattern comparable to that of old animals for mineral metabolism in brain,
      whereas in bone and testes the pattern of accumulation was closer to that of
      young rats. While the urinary levels of Ca were generally reduced in the Al
      exposed groups, no Al-associated changes were noted for Mg, Mn, Cu and Zn. In
      turn, after 6.5 months of Al administration Fe excretion was increased in Al
      treated adult and old rats. The results of this study suggest that early stages
      of life cycle should be of special concern for Al-induced changes in the
      metabolism of essential elements.

PMID- 9148277
TI  - Prejunctional modulation by prostaglandin E2 of noradrenaline release from
      sympathetic neurones in rabbit aorta.
AB  - The modulating effect of prostaglandin E2 (PGE2) on the electrically-evoked 3H
      overflow from rabbit isolated aorta preloaded with 3H-noradrenaline was examined.
      PGE2 (3 x 10(-9)-3 x 10(-7) M) inhibited the stimulation-evoked 3H-overflow
      (maximum inhibition: 81%; pIC50: 8.1). The inhibition was reversible and
      inversely related to stimulation frequency (1-30 Hz). Cocaine (3 x 10(-5) M) and
      corticosterone (4 x 10(-5) M) did not alter the inhibitory effect of PGE2 (3 x
      10(-9)-10(-7) M). Rauwolscine (10(-6) M) enhanced the reduction caused by PGE2 (3
      x 10(-9)-10(-7) M). Rauwolscine (10(-6) M) alone enhanced the 3H-overflow by
      360%. Indomethacin (3 x 10(-6) M) and suprofen (4 x 10(-5) M) did not alter the
      PGE2 (3 x 10(-9)-10(-7) M)-induced reduction of the 3-H-overflow. Indomethacin (3
      x 10(-6) M) and suprofen (4 x 10(-5) M) alone had no effect. We conclude that in
      the rabbit aorta (1) PGE2 modulates noradrenaline release from sympathetic
      neurones through a prejunctional inhibitory receptor mechanism; (2) that there is
      an interaction between alpha 2-adrenoceptors and EP-receptors; (3) that uptake
      inhibition does not affect the effect of PGE2; and (4) that the influence of
      endogenous prostaglandins on the noradrenaline release can be excluded.

PMID- 9148278
TI  - Drugs that influence tubulin polymerization modulate thyrotropin-releasing
      hormone receptor number in AtT-20 cells.
AB  - In order to examine the role of cytoskeleton in modulating the cell surface
      receptors, AtT-20 cells (stably expressing thyrotropin-releasing hormone
      receptors) were incubated with drugs that are known to modify the tubulin
      microtubule system. The binding of [3H]methyl thyrotropin-releasing hormone
      ([3H]mTRH) to intact cells increased as a function of time, and was linear from
      1.25 x 10(6) to 6.25 x 10(6) cells/ml. Cells incubated with colchicine,
      vinblastine, and taxol for 16 hr were harvested and the cell concentration was
      determined using a haemocytometer. Because the drugs inhibited the cell
      proliferation at 100 nM, it was decided to examine the effect of 100 nM of each
      of the three drugs on the ability of [3H]mTRH to bind cell surface receptors.
      Cells were incubated with the drugs for 16 hr at 37 degrees. After the
      incubation, cells (5 x 10(6) cells/ml) from each group were assayed for [3H]mTRH
      binding. Colchicine, vinblastine, and taxol stimulated [3H]mTRH binding by up to
      27, 27, and 21%, respectively, without altering the Ka of the ligand to the
      receptor. These results suggest that perturbation of cytosolic microtubules leads
      to a reorganization of the spatial location of hormone receptors.

PMID- 9148279
TI  - Laboratory animal science, welfare and ethics in pharmacology and toxicology.

PMID- 9148280
TI  - Modulation by the endothelium of the inhibitory effects of pinacidil and
      nimodipine on endothelin-induced contraction in cerebral arteries.
AB  - The effects of pinacidil and nimodipine on endothelin-1-induced contractions in
      isolated cerebral arteries with and without endothelium were compared. The
      sensitivity to endothelin-1 was increased (0.5 log units) in the rabbit basilar
      artery after removal of the endothelium. The nitric oxide synthase inhibitor N
      omega-nitro-L-arginine (0.1 mM) also increased the sensitivity to endothelin-1
      (0.6 log units) in basilar arteries with endothelium, whereas N omega-nitro-D
      arginine (0.1 mM) and indomethacin (3 microM) had no effect, indicating that
      withdrawal of endothelium-derived nitric oxide may account for the enhancement of
      the endothelin-1-induced contraction after endothelial denudation. Pinacidil (1
      microM) shifted the concentration-response curve for endothelin-1 to the right
      without affecting the maximal response in arteries without endothelium, but had
      no effect on the endothelin-1-induced contraction in vessels with endothelium.
      Nimodipine (1 microM) reduced the maximal endothelin-1-induced contraction by
      approximately 50% in both the presence and absence of endothelium, whereas the
      sensitivity to endothelin-1 was reduced only in vessels without endothelium.
      Incubation in "calcium-free" medium reduced the maximal endothelin-1-induced
      contraction by 69% and 80% in vessels with and without endothelium, respectively.
      In human pial arteries with endothelium, pinacidil did not affect the endothelin
      1-induced contraction, whereas nimodipine and exposure to "calcium-free" solution
      reduced the maximal response by 31% and 74% respectively. The results show that,
      in the rabbit, pinacidil and to a lesser extent nimodipine preferentially act on
      cerebral arteries with disrupted endothelium, indicating that vasoactive factors
      liberated from the endothelium may modify the effect of a vasodilator.

PMID- 9148281
TI  - Differential effects of increasing doses of alpha-trinositol on cerebral blood
      flow autoregulation.
AB  - The effect of neuropeptide Y inhibition with alpha-trinositol on the cerebral
      blood flow autoregulation was studied in Wistar Kyoto rats. alpha-Trinositol was
      tested in two doses: one dose (5 mg kg-1 hr-1) selectively affecting neuropeptide
      Y and one higher dose (50 mg kg-1 hr-1) affecting both neuropeptide Y and the
      adrenergic response. The cerebral blood flow was measured with the intracarotid
      133xenon injection method in halothane nitrous oxide-anaesthetized animals. Blood
      pressure was raised by norepinephrine infusion and lowered by controlled
      haemorrhage in separate groups of rats. In addition we examined the effect of
      alpha-trinositol on neuropeptide Y-induced contraction of cerebral vessels in
      vitro. The in vitro study demonstrated inhibition of neuropeptide Y-induced
      contraction with a alpha-trinositol dose selective of neuropeptide Y. The in vivo
      study demonstrated that cerebral blood flow autoregulation was preserved after
      both doses of alpha-trinositol. alpha-Trinositol in the low neuropeptide Y
      selective dose (5 mg kg-1 hr-1) did not affect the blood pressure limits of
      cerebral blood flow autoregulation, but the higher dose (50 mg kg-1 hr-1) of
      alpha-trinositol shifted the upper blood pressure limit of cerebral blood flow
      autoregulation towards lower blood pressures, an effect probably due to
      inhibition of both the adrenergic and neuropeptide Y systems.

PMID- 9148282
TI  - Propofol-induced ataxia and hypnosis in rat lines selected for differential
      alcohol sensitivity.
AB  - An alcohol-sensitive rat line, selectively bred for high sensitivity to ethanol
      induced motor impairment, also exhibits greater sensitivity to gamma-aminobutyric
      acid type A (GABAA) receptor agonists, such as benzodiazepines and barbiturates,
      than an alcohol-insensitive rat line. We have investigated whether this
      difference was also maintained for the most recent intravenous anaesthetic,
      propofol. Propofol (100 mg/kg, intraperitoneally) induced similar sleep times and
      produced identical plasma propofol concentrations in alcohol-sensitive and
      alcohol-insensitive rat lines. At lower doses (50 and 75, but not 25 mg/kg),
      propofol produced a greater motor impairment in a tilting plane test in alcohol
      sensitive than alcohol-insensitive rats shortly after the injection. Binding of a
      convulsant, [35S]t-butylbicyclophosphorothionate, to cerebellar and
      cerebrocortical GABAA receptors in the presence of 2 microM GABA was similarly
      affected by low micromolar propofol concentrations in both rat lines, while in
      the absence of GABA, propofol was slightly less potent in the alcohol-sensitive
      than alcohol-insensitive line. These data indicate that alcohol-sensitive rats
      show transiently enhanced sensitivity to an ataxic, but not to a hypnotic dose of
      propofol, which cannot be explained by sensitivity differences to propofol in
      GABAA receptors determined in a binding assay using brain membrane homogenates.

PMID- 9148283
TI  - Proliferation and differentiation of cultured human keratinocytes is modulated by
      1,25(OH)2D3 and synthetic vitamin D3 analogues in a cell density-, calcium- and
      serum-dependent manner.
AB  - The natural form of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) decreases
      proliferation and promotes terminal differentiation of cultured human epidermal
      keratinocytes. The purpose of this study was to find out to what extent the
      culture conditions determine the sensitivity of keratinocytes to 1,25(OH)2D3 and
      synthetic vitamin D analogues. Human keratinocytes were grown in microplates.
      Cell proliferation (MTT-assay) and differentiation (quantity of transglutaminase
      type I) were measured consecutively in the same monolayer. When vitamin D3
      analogues were added to 50-60% confluent keratinocytes grown in serum-free
      keratinocyte growth medium with 0.09 mM Ca2+, stimulation of the proliferation
      was either minimal or non-existent, while differentiation was unaffected or
      slightly inhibited. There was no difference in the sensitivity to 1,25(OH)2D3 and
      the vitamin D3 analogues. When 1,25(OH)2D3 was added to less confluent
      keratinocytes (30%) a marked antiproliferative effect was observed. Addition of
      3% charcoal stripped foetal calf serum further enhanced the antiproliferative
      effect of 1,25(OH)2D3, and a difference in the sensitivity of the vitamin D3
      analogues was noted. If, finally, the Ca2+ concentration was raised to 0.3 mM,
      1,25(OH)2D3 and the vitamin D3 analogues stimulated differentiation. Also, a
      biphasic effect on proliferation occurred: stimulation at low vitamin D
      concentrations and inhibition at higher concentrations. Furthermore,
      keratinocytes became more sensitive to the synthetic vitamin D3 analogues than to
      1,25(OH)2D3: KH1060 > EB1089 > GS1500 > or = EB1213 > calcipotriol > 1,25(OH)2D3.
      For all compounds tested differentiation occurred at concentrations 10 to 30
      times lower than for proliferation. These results indicate that the sensitivity
      to vitamin D3 analogues as well as the direction of the response to vitamin D3
      analogues is dependent on the keratinocyte density, the availability of serum and
      Ca2+ concentrations.

PMID- 9148284
TI  - Opposite influences of different adrenoceptors on baclofen-induced
      antinociception in mice.
AB  - In the present study, the effects of adrenoceptor agonists and antagonists on
      baclofen-induced antinociception was investigated. Intraperitoneal administration
      of different doses of baclofen (2.5, 5 and 10 mg/kg) induced antinociception in
      the tail-flick test. The response was dose-dependent. The alpha 2-adrenoceptor
      agonist, clonidine, increased, while the alpha 1-adrenoceptor agonist,
      phenylephrine, decreased the baclofen response. In reserpine-treated animals,
      alpha 2-adrenoceptor, clonidine, induced antinociception and increased that of
      baclofen. Yohambine and propranolol but not prazosin decreased the baclofen
      effect. Although phenoxybenzamine itself induced antinociception it did not alter
      the baclofen response significantly. Reserpine treatment decreased the response
      induced by single administration of baclofen or phenoxybenzamine and that induced
      by a combination of baclofen with either phenoxybenzamine or prazosin. It may be
      concluded that alpha 2-adrenoceptor stimulation increases, while alpha 1
      adrenoceptor activation decreases the baclofen-induced antinociception, and
      aminergic mechanism(s) may have a positive influence on baclofen response.

PMID- 9148285
TI  - Objective detection of faking on role-play tests of assertion: gender
      differences.
AB  - The validity of role-play tests of assertiveness can be reduced by the effects of
      faking. Kern demonstrated that faking could be detected using assessors' global
      judgements. The present analysis is based on Kern's 1994 videotapes, examining
      the effectiveness of more objective measures. Undergraduates who were low in
      assertiveness and instructed to fake high assertiveness on the Idiographic Role
      play Test (n = 23) emitted more statements indicative of social-evaluative
      concerns than the veridically highly assertive testees (n = 27). Significant
      gender differences in the detectability of faking were also obtained. Whereas 24
      female fakers and nonfakers were differentiated via verbalizations of likability,
      26 male fakers and nonfakers were differentiated via empathic-assertive
      statements. The implications and limitations of this method to detect faking are
      discussed.

PMID- 9148286
TI  - Prescription privileges: a dearth of confidence in psychological interventions.
AB  - Summary.-Starker and Pankratz (1996) reported that psychologists have very high
      confidence in the efficacy of psychotropic medications relative to psychological
      interventions. In this paper it is argued that this lack of professional self
      confidence is the central dynamism in the prescription privileges movement.

PMID- 9148288
TI  - Content differences in suicide notes by gender and age: serendipitous findings.
AB  - In a sample of 40 German suicide notes, no gender differences were identified.
      Suicide notes of older people had fewer feelings of inadequacy and more
      indications of illness and grief over widowhood.

PMID- 9148287
TI  - Habit-specific locus of control scales for drinking, smoking, and eating.
AB  - The internal consistencies of three habit-specific locus of control scales
      measuring drinking, smoking, and eating behavior were evaluated using coefficient
      alpha. The three scales, along with Rotter's 1-E scale, were administered to 202
      undergraduate students. Estimates indicated the scales showed reasonably high
      internal consistency. Scores on the smoking and drinking scales had the lowest
      correlations with scores on Rotter's generalized measure. Mean drinking scale
      scores were lower than those for smoking and eating, suggesting that people judge
      drinking to be under more personal control. The implications of habit-specific
      expectancies, particularly with regard to habit disorders, are discussed.

PMID- 9148289
TI  - Content analysis of gay male and lesbian personal advertisements.
AB  - 396 randomly selected gay and lesbian personal advertisements were analyzed for
      content. Analysis supported the hypotheses that the 198 men are more interested
      in sexuality and physical attractiveness, while the 198 women are more concerned
      with the personality characteristics of prospective partners.

PMID- 9148290
TI  - Assessing variability of HIV transmission attitudes and behaviors at an urban
      northeastern university.
AB  - Teenagers in the United States are one of the populations whose HIV infection
      rates are increasing most rapidly. This study was designed to measure college
      students' knowledge of HIV transmission methods using Kittleson and Venglarcik's
      HIV Transmission Survey. Participants (N= 167) were divided into two groups, 99
      students from a rural background and 68 students from an urban background.
      Students from an urban background were significantly more knowledgeable about
      documented HIV transmission modes than students from a rural background. Men were
      significantly less aware of documented HIV transmission modes than women. These
      results suggest that education about AIDS needs to be improved. The current
      educational procedures do not properly inform students in a fashion which
      exhibits the true risk of infection and those behaviors which increase risk.
      Fifteen years after the discovery of the HIV virus students are still largely
      unaware that they are at risk for contracting a fatal disease.

PMID- 9148291
TI  - Divorce versus intact parental marriage and perceived risk and dyadic trust in
      present heterosexual relationships.
AB  - The relationship between parental divorce and intimate relationships in late
      adolescence was estimated for 60 undergraduates (17 men, 43 women). Subjects from
      divorced families were assessed to address whether they perceived their present
      heterosexual relationship to be risky and if they were less trusting of their
      partners than were subjects from intact families. Divorce appears to be
      transmitted through generations in a family. Dyadic Trust and Perceived Risk were
      investigated as two learned components passed down within families, thereby
      contributing to a cycle of divorce. A correlation was found between parents'
      marital status and children's trust in their dating partners. An inverse
      relationship was indicated; when ratings of trust are low, ratings of perceived
      risk are high. A possible order of this relationship was discussed, i.e., low
      dyadic trust preceded perceived risk. One implication of these findings was that
      children of divorced parents may benefit from being shown how failures in
      relationships may result from negative expectations.

PMID- 9148292
TI  - Environment is not the most important variable in determining oral morphine
      consumption in Wistar rats.
AB  - The role of differential housing on sucrose-morphine consumption in outbred
      Wistar rats was investigated in two studies. The results of earlier research,
      indicating rats housed in a quasinatural colony drank significantly less sucrose
      morphine than rats isolated in standard laboratory cages, could not be
      replicated, as the consumption of sucrose-morphine by the isolated animals in the
      present two studies was reduced. It is possible that during a colony conversion
      the supplier inadvertently introduced strain differences making the present rats
      more resistant to xenobiotic consumption. Discussion documents the role of
      genetics in morphine consumption.

PMID- 9148293
TI  - Narcissism and birth order.
AB  - The purpose of this investigation was to clarify the relationship between birth
      order position and the development of narcissism, while refining research and
      theory. The relationship between birth-order status and narcissism was examined
      with a sample of 79 undergraduate students (55 women and 24 men). These subjects
      were placed in one of the four following birth-order categories of firstborn,
      second-born, last-born, and only children. These categories were chosen given
      their significance in Adlerian theory. Each subject completed the Narcissistic
      Personality Inventory and a demographic inventory. Based on psychodynamic theory,
      it was hypothesized that firstborn children were expected to score highest, but
      statistical significance was not found for an association between narcissism and
      birth order. Further research is urged to investigate personality theory as it
      relates to parenting style and birth order.

PMID- 9148294
TI  - Attitudes and observations about nonverbal communication in the psychotherapeutic
      greeting situation.
AB  - A survey of 209 licensed, psychotherapists was conducted to investigate attitudes
      towards and observations of nonverbal communication in a reference situation.
      Background factors such as gender, years of psychotherapeutic experience, hours
      of therapy practiced each month, and theoretical approach were used to examine
      relationships. The psychotherapeutic greeting situation, i.e., the first time a
      therapist and patient meet in a waiting room, was chosen as the reference
      situation. Female psychotherapists believed that nonverbal communication was more
      important than male psychotherapists. Psychotherapists with 16 years or more
      experience supported items that constitute the greeting phase and items on active
      observation significantly more often than psychotherapists with less experience.
      Hours of psychotherapeutic practice and frames of reference were not
      significantly related to any item within the questionnaire. Belief in nonverbal
      communication was not significantly related to items that involve preparing to
      meet a patient for the first time.

PMID- 9148295
TI  - Computer use in schools for the blind in Japan.
AB  - In a school for the blind, computer use and feelings toward computers by 34
      visually impaired students receiving secondary education and by their 42 teachers
      were investigated with a questionnaire. Most subjects used computers effectively,
      but some students who had low vision did not wish to use them to avoid strain on
      their eyes. The computers allowed use of Kanji (Chinese characters) by the blind
      students, providing a new tool in their learning of Kanji. In classes, it is
      necessary to maintain and customize the computers continuously.

PMID- 9148296
TI  - Religiosity in adolescence and young adulthood: implications for identity
      formation.
AB  - Based on previous correlations between religiosity and descriptions of character
      traits related to meaning and purpose in life described by Gladding, et al. in
      1981, this study hypothesized significant differences in religiosity scores as a
      function of age. Variables of religious group and gender were also included.
      Subjects included 147 adolescents and young adults, 70 males and 77 females,
      largely Caucasian, attending fundamental, moderate, and liberal churches in
      Central and Northwest Arkansas. A 3 x 3 x 2 analysis of variance yielded
      significant main effects for age group and religious group but not gender. No
      interactions were found. Findings suggest relationships between religiosity and
      identity formation during adolescence.

PMID- 9148297
TI  - Weinberger adjustment typology and the five factor model of personality.
AB  - Construct validity of Weinberger's Six-group Typology of Adjustment was
      investigated by testing the hypothesis that the six personality types have
      different personality profiles. The Weinberger Adjustment Inventory and the
      Revised NEO Personality Inventory were completed by 170 psychology undergraduates
      (84 men and 86 women). Results strongly supported the tested hypothesis.

PMID- 9148298
TI  - Cross-cultural adjustment of Chinese students in Japan.
AB  - The present study examined responses of 92 Chinese students in Japan to
      questionnaires which included adjustment items selected from work of Baker in
      1981 and Uehara in 1988. These items were classified by factor analysis into four
      scales of Emotional, Academic, Cultural-Social, and Environmental. Adjustment
      scores on the Environmental scale were higher than those on the other three
      scales. Country of origin was a significant influence only for scores on the
      Environmental scale. Students who came from Taiwan scored higher on adjustment.
      There were gender differences on Emotional and Academic scales; male students
      reported higher adjustment. The effects of students' length of residence and
      proficiency in the Japanese language could be seen in scores on Academic and
      Cultural-Social scales; the students who had a longer period of stay or had
      higher proficiency in Japanese language had higher scores on adjustment. Thus,
      results indicated that personal differences were reflected in subfactors of
      adjustment.

PMID- 9148299
TI  - Prescription privileges and training issues: a pilot study.
AB  - Despite all the rhetoric on the controversial issue of prescriptive authority for
      psychologists, we posit that the major factor will be one of adequate training
      standards. As several training models have involved lengthy and rigorous
      curriculum formats, we conducted a brief pilot study on the views of practicing
      psychologists. Only one of the 20 licensed psychologists in our sample was
      willing to undertake an intensive one- to two-year program in psychopharmacology
      at this stage of their careers.

PMID- 9148300
TI  - Robustness of the Photo Anxiety Questionnaire: changing the sequence of stimuli
      and photographs.
AB  - In a split-ballot experiment (N=458) we tested, first, to what extent the logical
      presentation of the Photo Anxiety Questionnaire forces respondents into the usual
      response pattern, that is, a higher reported anxiety on items mentioning a time
      closer to dental treatment. Secondly, we tested whether subjects use the
      nonverbal response scale or merely use the position of the photographs on the
      scale when answering the questions. The original questionnaire had the highest
      reliability and was least influenced by response bias. Changing the order of the
      photographs on the response scale did not alter the response pattern, implying
      that subjects do react to the intensity displayed in the photographs and not just
      to the position of the photograph on the scale. Because changing the order of the
      items altered the response pattern only marginally, the response pattern usually
      found does not seem to be the direct consequence of the logical presentation of
      the Photo Anxiety Questionnaire.

PMID- 9148301
TI  - The Rorschach in contemporary forensic psychology.
AB  - Recent empirical data attest to the fact that the Rorschach is frequently used in
      expert witness testimony. Popularity of the Rorschach in forensic psychology is
      evident in the Psychological Abstracts database.

PMID- 9148302
TI  - Adolescence and diagnostics.
AB  - The major diagnostic categories (schizophrenia, borderline disorder, depression)
      are reviewed and the difficulties in applying this "adult" classification to
      adolescence are noted. The reasons for these are numerous, i.e., history of the
      discovery of diseases, the similarities in psychodynamic functioning between the
      pathological and the "normal" in adolescence, and prognosis which varies
      depending on age. How, then, does one distinguish between the pathological and
      the normal at this age, and is the concept of crisis at all useful?

PMID- 9148303
TI  - Companion animals and the psychological health of Alzheimer patients' caregivers.
AB  - A sample of 244 persons in northern California who provided care for individuals
      with possible or probable Alzheimer's disease was studied to examine the effect
      of association with companion animals on three indices of psychological health.
      124 caregivers had regular contact with pets; 120 caregivers did not. Men who
      were attached to dogs scored better on some measures of psychological health than
      did men who had no pets. Women less than 40 years old who were attached to cats
      scored better on some measures of psychological health than did the same-age
      women who had no pets. Women aged 40 to 59 years who were attached to dogs scored
      worse on measures of life satisfaction and depression than did the same-age women
      who had no pets. The data suggested a positive indirect effect on caregivers'
      mental health through interaction between the pet and the patient, but small
      strata numbers precluded definitive conclusions. Association with pets appeared
      to temper some of the psychological stress associated with caring for a
      cognitively impaired adult among young female and male caregivers but not among
      middle-aged female caregivers.

PMID- 9148304
TI  - Note on forced institutional relocation of nursing home residents.

PMID- 9148305
TI  - Subclinical depressive symptoms in HIV are related to avoidance coping responses:
      a comparison with end-stage renal failure and breast cancer.
AB  - We examined the relationship between coping responses and mood states among three
      samples of patients with human immunodeficiency virus (HIV) infection (n=26), end
      stage renal failure (n=98), and breast cancer (n= 60). Avoidance scores differed
      significantly across the groups, being highest in those with HIV infection. The
      avoidance scores were significantly and positively correlated with depression
      scores. However, patients with HIV infection did not fulfill the diagnostic
      criteria for major depression. Although patients with HIV infection may have
      minor psychiatric symptoms, results suggest that the symptoms are not strong
      enough to warrant a psychiatric diagnosis of mood disorder. It might be
      clinically important to attend to avoidance behaviors and thoughts which may
      develop into the manifestation of depression.

PMID- 9148306
TI  - Risk-taking behavior: a cognitive approach.
AB  - In examining the associations of critical thinking skills and risk-taking
      behavior, scores on the Sensation Seeking Scale, Form V, Rotter's I-E Scale, and
      the Cornell Critical Thinking Scale confirm earlier research on sensation seeking
      in pointing to gender differences that predict more risk-taking behavior by men
      (n = 52) than women (n = 48).

PMID- 9148307
TI  - Convergent validity of the depression-happiness scale with the Crown-Crisp
      experimental index.
AB  - In recent years the study of subjective well-being has attracted much research
      interest. A 1993 operational definition is the Depression-Happiness Scale of
      McGreal and Joseph. The aim of the present research was to investigate the
      convergent validity of the Depression-Happiness Scale with the Crown-Crisp
      Experiential Index. Among 40 undergraduate university students, higher scores on
      the Depression-Happiness Scale were significantly associated with lower scores on
      Free floating anxiety (-.63), Somatic anxiety (-.56), Depression (-.78), and
      Hysteria (-.36) scales but not the Phobic anxiety (-.27) or Obsessionality (-.25)
      scales of the Crown-Crisp Experiential Index. These data provide further evidence
      for the convergent validity of the Depression-Happiness Scale.

PMID- 9148308
TI  - Pragmatism and the cognitive and neural sciences.
AB  - Two prominent intellectual disciplines dominate the discipline of psychology, the
      cognitive and neural sciences. Separate departments for both are now commonplace
      at major universities across America. I suggest, however, that the discipline of
      psychology asks key questions about experience, mind, or central states not found
      in other disciplines. Psychology is embodied in both the cognitive and neural
      sciences, and an important common thread is the Jamesian-Deweyian emphasis on
      experience. The Jamesian-Deweyian tradition emphasized the sense of experience in
      problem-solving and functional adaptations. The pragmatists' sense of experience
      is the way by which one engages the world, is inherently cognitive, and
      orchestrated by central states of the brain. Any attempt within the neural and
      cognitive sciences to capture human experience will need to resurrect this
      tradition.

PMID- 9148309
TI  - Diagnosis and treatment of depression by general practitioners in England.
AB  - This paper describes a preliminary study of diagnosis and treatment of depression
      by general practitioners in England. They regarded primary care depression as a
      reactive mood disorder with both physical and psychological symptoms and
      associated with those groups who are most vulnerable to life stressors. Four
      groups were seen as at risk from depression: elderly persons, menopausal women,
      young mothers, and those in early adulthood. The practitioners relied primarily
      on their experience to diagnose depression rather than following any official
      diagnostic criteria. Although they were in favour of nondrug therapy in treating
      depression, they mainly practised drug therapy due to time pressure and limited
      availability of resources.

PMID- 9148310
TI  - Prevalence and course of posttraumatic stress disorder in Dutch veterans of the
      civilian resistance during World War II: an overview.
AB  - This study concerns the prevalence of current and lifetime Posttraumatic Stress
      Disorder (PTSD) in various groups of officially recognized Veterans of the Dutch
      civilian Resistance against the Nazi occupation during World War II. In total,
      1046 Resistance veterans living in The Netherlands and 52 who immigrated to the
      United States after the war were examined. Between four and five decades after
      the end of WW II, between 25 and 50% were suffering from current PTSD. The life
      time prevalence is estimated to be substantially higher. The course of PTSD
      proved highly variable. There had often been a delay of several decades between
      the end of the war and reoccurrence or first onset of posttraumatic symptoms. The
      prevalence of PTSD in Resistance veterans who emigrated to the United States was
      hardly different from that of the veterans still living in The Netherlands.

PMID- 9148311
TI  - Self-statements, self-esteem, and locus of control in discriminating college
      students' scores on the Beck Depression Inventory.
AB  - To study the use of the ratio of positive to negative self-statements, locus of
      control, and self-esteem in discriminating between scores on the Beck Depression
      Inventory 145 undergraduate college students were administered the Beck
      Depression Inventory, Automatic Thoughts Questionnaire-Revised, Coopersmith Self
      esteem Inventory-Adult Form, and the Rotter Locus of Control scale in their
      classrooms. A stepwise discriminant analysis indicated that five variables
      combined to yield a statistically significant discrimination among low, middle,
      and high scores on the Beck Depression Inventory. The classification analysis
      indicated that 77.1% (n = 111) of the undergraduate students were correctly
      classified; 93.2% (82 of 88) were correctly classified as low scorers and 73.3%
      (18 of 46) were correctly classified as high scorers.

PMID- 9148312
TI  - A pilot study of nonverbal cues in videotelecommunication.
AB  - With the increasing popularity of low-cost videocommunications systems and their
      attendant low bandwidth-resolution problems, receivers are likely to experience
      difficulties in recognising the sender's intended expression and feeling. As an
      extension of previous work in the area, this pilot study investigated the effects
      of three forms of degraded imaging (and their combined effects) on the nonverbal
      aspects of communication for one person. Degraded video messages significantly
      impaired the meaning of the sender.

PMID- 9148313
TI  - Scores on the California Psychological Inventory for men and women majoring in
      counseling.
AB  - Mean scores of 49 counseling majors on the California Personality Inventory
      indicated the 13 men showed more favorable personal characteristics than the 36
      women.

PMID- 9148314
TI  - Counselors' adjective correlates of working alliance.
AB  - The authors present a study of 85 counselors' adjective descriptors of clients in
      relation to a working alliance. The imperative for such a study emerges from
      Cough's 1965 Conceptual Analysis of Test Scores approach to clinical measurement.
      For this investigation, all 300 items of the Adjective Check List were used.
      Working alliance was measured by the counselor's form of the Working Alliance
      Inventory-Short. Point biserial correlation of each adjective with inventory
      scores produced 54 significant adjectives. These 54 adjectives were 18 times the
      number expected by chance.

PMID- 9148315
TI  - Perceptions by adult children of elderly parents' needs.
AB  - The purpose of this study was to examine the accuracy of adult children's
      perceptions of their elderly parents' concerns. Factors associated with moderate
      involvement between the elderly parent and adult child were predicted to lead to
      the greatest accuracy. 48 pairs of elderly parents and adult children filled out
      questionnaires regarding the parents' concerns about seven areas of functioning.
      Analysis showed that concerns about health and emotional support were rated as
      most important by elderly parents. Adult children accurately perceived these
      concerns to be most important to their parents. For health concerns, opposite-sex
      pairs of parents and children showed greatest agreement. For emotional support
      concerns, however, both sons and daughters were more accurate predicting their
      fathers' concerns than their mothers'. Middle-born children tended to be more
      accurate in their predictions of parents' concerns than oldest or youngest
      children. Living arrangements also influenced accuracy. In predicting the
      concerns of elderly parents, adult children were most accurate for parents living
      in retirement communities, moderately accurate for parents living independently,
      and least accurate for parents living in the adult child's home. Further,
      children sharing a household with an adult parent tended to overestimate their
      parents' concerns on some issues. The results were consistent with the moderate
      involvement hypothesis. The implications of these results and suggestions for
      research are discussed. A version of this paper was presented at the Ninety-ninth
      Annual Convention of the American Psychological Association in San Francisco,
      August 18, 1991.

PMID- 9148316
TI  - Predicting the rate with which law enforcement officers are murdered.
AB  - In a time-series study of data from 1961 to 1985, the rate with which American
      police officers were killed by civilians was best predicted by the general
      homicide rate and the rate of justifiable homicide by police officers.

PMID- 9148317
TI  - Contextual effects on adolescent disorders relevant to coping.
AB  - A four-factor control model was used to test the contextual determinants in
      adolescents' sense of control on a coping scale. Outpatients, matched for age and
      gender, completed the Tiffany Control Scales. Analyses confirmed the hypotheses
      that 52 who scored as externalizing compared to those 40 scoring as internalizing
      showed greater coping in response to different contextual determinants defined as
      situations.

PMID- 9148318
TI  - The face of AIDS: Effects of physical attractiveness and target gender on
      inferred mode of HIV infection.
AB  - We examined the effects of physical attractiveness on the assumed mode of HIV
      acquisition. 176 students read a description of an HIV-positive target whose
      photograph was placed above the description. A 2 (target gender) by 2 (attractive
      or unattractive target) factorial design was used. Unattractive targets were
      perceived as more likely to have acquired HIV through homosexual relationships.
      Further, men were perceived as more likely than women to have acquired HIV
      homosexually. Attractiveness did not bias health-care allocations regarding the
      infected target.

PMID- 9148319
TI  - Depression and dissociation as features of borderline personality disorder in
      hospitalized adolescents.
AB  - 26 adolescents showing Borderline Personality Disorder were compared with 12
      carrying other diagnoses to clarify associated features of these conditions. In
      line with recent literature, the borderline adolescents evidenced significant
      depression and dissociation, suggesting the importance of evaluating instability
      of mood (versus thinking) and weak continuity in self-experience when identifying
      and treating this disorder.

PMID- 9148320
TI  - Confounded versus nonconfounded correlations among the neo-personality
      inventory's domain and facet scales.
AB  - The 18 subscales constituting the Neuroticism, Extraversion, and Openness domain
      scales of Costa and McCrae's NEO-Personality Inventory were correlated with all
      five NEO-PI domain measures using data from 303 university students. Their
      residual domain scale scores correlated less than .50 with those on nine facet
      scales. A divergent domain scale correlated + or - .30 or more with 11 facets,
      including correlations of -.34 or more by Conscientiousness with the
      Impulsiveness, Vulnerability, and Depression facets of neuroticism. These latter
      values were even stronger in the NEO-Personality Inventory-Revised. The
      correlation of a facet scale with its preassigned residual domain scale and with
      a divergent domain scale did not differ significantly in 6 of the 18 cases.
      Unconfounded (part vs whole-minus-part) correlations had a median value of .52
      versus .68 for their confounded (part vs whole) counterparts. A full report of
      unconfounded correlations clarifies the structure of composite personality
      measures.

PMID- 9148321
TI  - Pathological gambling and depression.
AB  - A number of previous studies have indicated that pathological gambling is often
      associated with depression. Equally, a number of theoretical models of
      pathological gambling have included depression as a key variable. Here we report
      a study of depression in pathological gamblers identified within a random sample
      of 1,615 adults living in the major cities of Galicia (northwest Spain).
      Pathological gamblers were identified on DSM-IV diagnostic criteria. Depression
      was evaluated with the Beck Depression Inventory, subjects being classified
      'depressive' if they obtained a score of 18 or more. Of 19 pathological gamblers
      who completed the Beck Depression Inventory, 21% were depressive; by contrast,
      only 9% of the other subjects were depressive. The Beck scores of pathological
      gamblers were positively correlated with the severity of their addiction as
      indicated by the number of DSM-IV-specified symptoms reported.

PMID- 9148322
TI  - Alexithymia in substance abuse: relationship to depression.
AB  - Recently Giannini reported that substance abusers were significantly higher
      alexithymic scorers than healthy volunteers but that the alexithymia scores
      correlated positively with scores of mood states on the five-factor model for
      healthy volunteers not but for substance abusers. This suggested that researchers
      should not aggregate all substance abusers into one group. To check Giannini's
      suggestions, further examinations including mood changes in substance abusers
      seem needed.

PMID- 9148323
TI  - Does self-concept depend on body image? A gender analysis.
AB  - The purpose of this study was twofold, to estimate positive correlations between
      scores on the Tennessee Self-concept Scale for body image and self-concept within
      each gender and to assess differences between genders on measures of these two
      concepts, thereby testing the hypothesis that women have a more diminished body
      image than men. The study included 36 subjects, 18 male and 18 female. Within
      each gender were significant and positive correlations between measures of body
      image and self-concept. Between the genders, there was no significant difference
      in scores on self-concept but there was a difference in ratings of body image,
      with women being significantly less satisfied.

PMID- 9148324
TI  - Gender differences in attitudes and recruitment into psychiatry.
AB  - Factors in change of attitude toward psychiatry and encouragement of women into
      the field are mentioned.

PMID- 9148325
TI  - Discriminant analyses of willingness to talk with a counselor and most difficult
      issues in the experience of unsheltered homeless men: self-actualization,
      loneliness, and depression.
AB  - Stepwise discriminant analyses of willingness to talk with a counselor (Wilks
      Lambda=.75, p<.001) and most difficult issues (Wilks Lambda=.81, p<.001) in 145
      unsheltered homeless men's experience were examined using self-actualization
      constructs, loneliness, depression, and history-of-being-homeless variables. For
      example, homeless men with higher scores on loneliness, autonomy, courage, Jonah
      Complex, and self-acceptance were less willing to talk with a counselor. The
      variable, longer intervals of having a home after a first homeless episode, was
      associated with personal issues rather than with homeless issues. Selected
      participants' responses to the items, "what have you learned from your homeless
      experience that you could not have learned any other way" and "what would you
      like for me to know about your experience of homelessness," are posted to give
      perspective on a homeless person's internal frame of reference. This
      phenomenological approach indicated strengths as well as weaknesses of homeless
      men. Counseling programs should embrace all homeless persons including mentally
      well, nondrug-dependent homeless individuals.

PMID- 9148326
TI  - On sin, symptom substitution, and simplicity: a response to "preventing relapse
      in weight control".

PMID- 9148327
TI  - A comment on DSM-IV's diagnostic taxa.
AB  - It is suggested that the current American Psychiatric Association's diagnostic
      and statistical manual does not distinguish between natural or identity
      categories and artificial or equivalence categories and that, while this has
      facilitated research on social policy, it has hampered the development of
      therapies.

PMID- 9148328
TI  - Cattell's 16 PF and PSY inventory: relationship between personality traits and
      behavioral responses in patients with acute myocardial infarction.
AB  - The aim of this study was to investigate the relationships between personality
      and behavioral responses in patients with acute myocardial infarction. In a first
      step, a new instrument (PSY Inventory) for assessment of six behavioral
      characteristics (Sense of Responsibility, Energy and Competitiveness, Obsessive
      Behavior, Anger and Hostility, Stress-related Disturbances, Time Urgency) was
      developed by using factor analysis on intercorrelations of responses from 524
      subjects of the general population. Internal consistency reliability for each of
      the PSY subscales was estimated by Cronbach alpha coefficients. In a second step,
      the PSY Inventory was administered with the Cattell 16 PF Questionnaire to 838
      patients affected by acute myocardial infarction. Significant correlations
      although relatively low in magnitude for PSY Inventory subscales and certain
      scales of the Cattell 16 PF were found. With factor analysis on 22 variables
      (including the six PSY Inventory subscales and the 16 scales of the Cattell 16
      PF), five second-order factors were identified, namely, Extraversion, Neurotic
      Anxiety, Superego Strength, Pathemia, and Neurotic Hostility. While a Pathemia
      Factor (characterized by sensitivity, imagination, and self-sufficiency) was
      factorially independent of scales of the PSY Inventory, Extraversion, Neurotic
      Anxiety, Superego Strength, and Neurotic Hostility Factors were composed of the
      PSY Inventory scales and Cattell 16 PF scales combined. These relationships would
      reflect the concordance of internal constructs for behavioral measures of the PSY
      Inventory and those of personality traits of the 16 PF Questionnaire in patients
      with acute myocardial infarction.

PMID- 9148329
TI  - The last radiographer in America.

PMID- 9148330
TI  - Opportunities for specialized accreditation.

PMID- 9148331
TI  - Continuous quality improvement.

PMID- 9148332
TI  - [Anopheles (Culicidae, Anophelinae) and Malaria in Buriticupu-Santa Luzia, pre
      Amazonic Maranhao].
AB  - Seven species belonging the subgenus Nyssorhyncus were found. Anopheles (N.)
      darlingi, the principal vector of human malaria, was the most abundant (53.1%)
      followed by A. (N.) evansae (21.0%, A. (N.) triannulatus (17.4%) e A. (N.)
      nuneztovari (4.8%). The others, A. (N.) argyritarsis. A. (N.) oswaldoi and A.
      (N.) rangeli, were less frequently found, representing only 3.7% of the total
      sample. The anophelines were most frequent in both the extra (51.7%) and
      peridomiciles (45.7%). The intradomicile was visited by some specimens of the A.
      (N.) darlingi and A. (N.) evansae (active in both the rain and dry seasons,
      especially in the former, when the malaria reached high levels of transmission.

PMID- 9148333
TI  - [Survival of the hepatitis C virus in a dialysis population in Goiania, Goias].
AB  - The patients were 173, aged 10 to 70 years old. An Elisa II test was undertaken
      and 61 to 173 (35.3%) had positive test; when INNO-LIA test was made,
      soropositivity was 26% (44/173). Patients with anti-VHC antibodies have been kept
      on hemodialysis treatment for periods longer than negatives (p < 0.05). Neither
      drugs users, blood transfusions, sexual and aminotransferase activity were
      significantly correlated with the infection. There is an elevated prevalence of
      anti-VHC antibodies among chronic hemodialysis patients which seems to be related
      to the time that patients are on dialysis treatment.

PMID- 9148334
TI  - [Histoplasmosis in immunodepressed patients: study of 18 cases seen in
      Uberlandia, MG].
AB  - The diagnosis of histoplasmosis was made by isolation of Histoplasma capsulatum
      from cerebrospinal fluid (CSF), blood and bone marrow or by histopathologic
      (biopsy or post mortem) examination. The mean age of the patients was 35.8 years;
      13 patients were male (72.2%). The disease was disseminated, with the following
      distribution:skin (38.8%), bone marrow (27.7%), nasopharyngeal mucosa (22.2%),
      lungs (22.2%), colon (11.1%), central nervous system (5.5%) and esophagus (5.5%).
      Adenomegaly (50%), hepatomegaly (77.7%) and splenomegaly (61.1%) were frequently
      seen. The most common hematologic abnormality was pancytopenia (33.3%) of the
      patients. Eleven patients were treated, 9 with amphotericin B and 2 with
      itraconazole. Eight had good clinical improvement and all of them were given
      amphotericin B or a triazolic as maintenance therapy. This study emphasize the
      importance of this mycosis in immunodepressed patients, specially AIDS patients,
      in whom the infection tends to invade the macrophagic-lymphoid system and
      preferentially the cutaneous tegument.

PMID- 9148335
TI  - [Treatment of the mucosal form of leishmaniasis without response to glucantime,
      with liposomal amphotericin B].
AB  - We treated six patients with mucosal leishmaniasis who failed to respond to
      glucantime (20 mg/kg/day) with ambisome (2-5 grams total dose). The daily dose
      was 2-3 mg/kg/day given for a minimum of 20 days. After 26-38 months of follow
      up, five patients were clinically cured. One relapsed after six months. No side
      effects of therapy were observed apart from headache after infection. Ambisome is
      a therapeutic option for patients with mucosal leishmaniasis unresponsive to
      antimonials.

PMID- 9148336
TI  - [Anaerobic threshold detected using "V-slope analysis" in chronic chagasic
      disease].
AB  - Anaerobic threshold (AT) as measured by V-slope, is the best parameter of cardiac
      reserve in patients with heart failure. A reduction of AT reflects linearly a
      limited cardiopulmonary reserve in patients with heart disease. We measured the
      anaerobic threshold from 28 patients (18 men; age 47 +/- 6.7 years) classified
      into four groups: IA (normal ECG, without heart disease; 9 patients); IB (normal
      ECG, early left ventricular segmental abnormalities; 5 patients); II (abnormal
      ECG, advanced myocardial damage, no signs of heart failure, 7 patients); and III
      (abnormal ECG, end-stage, congestive heart failure; 7 patients). The analysis of
      variance indicated that the anaerobic threshold from patients of group LA was
      significantly greater than in groups IB, II and III (p = 0.001). Tukeys multiple
      comparison test showed no significative differences between mean AT in groups IB,
      II and III. The present study clearly demonstrates that occurrence of initial
      left ventricular contraction abnormalities is associated with definite reduction
      of cardiopulmonary reserve, and that this reduction is progressive and parallels
      the hemodynamic alterations. The most probable cause of this finding in group IB
      is diastolic dysfunction as clearly shown in echocardiogram.

PMID- 9148337
TI  - [Comparative controlled study on the use of benznidazole, nifurtimox and placebo,
      in the chronic form of Chagas' disease, in a field area with interrupted
      transmission. I. Preliminary evaluation].
AB  - A controlled clinical trial was carried out to evaluate the therapeutic efficacy
      and tolerance of nifurtimox and benznidazole in patients with chronic Chagas'
      disease. All patients had immunofluorescence and complement fixation reactions
      positives for T. cruzi antibodies and at least two xenodiagnoses positives in
      three performed before treatment, and they were submitted to clinical
      examinations, ECG and X-ray of the heart and esophagus. Of 77 patients studied,
      27 were treated with nifurtimox and 26 with benznidazole in the dosage of 5
      m/kg/day for 30 consecutive days, and 24 received a placebo in tablets similar to
      benznidazole. From the 77 patients, 64 (83.1%) accomplished the treatment: 23
      (88.4%) with benznidazole, 19 (70.3%) with nifurtimox and 22 (91.6%) with
      placebo. The patients were evaluated, clinically, serologically and
      parasitologically (six xenodiagnoses within one year after treatment). The
      benznidazole group showed only 1.8% of positive xenodiagnoses post-treatment, the
      nifurtimox 9.6% and the placebo 34.3%. All serologic reactions continued positive
      and there were no clinical, ECG or X-ray changes one year after treatment.

PMID- 9148338
TI  - [Inactivated vaccine against hepatitis A: review of the literature and
      considerations on its use].
AB  - A new, safe, highly immunogenic and probably long term effective inactivated
      hepatitis A virus vaccine has been licensed for clinical use. Clinical trials in
      developed countries have demonstrated its efficacy in preventing hepatitis A in
      high risk groups, such as travelers to regions where HAV infection is endemic and
      day care children and staff, its efficacy in postexposure conditions and in
      community outbreaks. The authors review the basic and changing features of the
      disease and its epidemiology in specific geographical regions trying to elucidate
      its use in the control of the disease in developing countries, especially in
      Brazil. Taking in consideration its efficacy, safety and immunogenicity, the
      inactivated hepatitis A vaccine may be of extreme value in terms of individual
      protection. Because this vaccine is so new, there are no formal recommendations
      for its use in developing countries, and appropriate public health use of
      hepatitis A vaccine requires up-to-date epidemiological information.

PMID- 9148339
TI  - [Evaluation of the quality of life in patients with Chagas' disease undergoing a
      heart transplant].
AB  - Quality of life was evaluated in 11 patients with Chagas' disease 26 to 126
      months after submission to heart transplantation. There was an objective
      improvement in their quality of life, after the transplant.

PMID- 9148340
TI  - [Is Trypanosoma cruzi a parasite].

PMID- 9148342
TI  - [High-frequency jet ventilation. An exciting technique now firmly established].

PMID- 9148341
TI  - [The influence of corticoids, in Chronic Chagas disease, administered in virtue
      of associated disorders].
AB  - Patients with chronic Chagas' disease and simultaneous medical problems treated
      with corticosteroid were studied in order to evaluate steroid influence on
      chronic Trypanosoma cruzi infection. Parasitological assessment, radiological and
      electrocardiographic studies as well as non specific tests were performed in
      patients and in a control group that included chronic infected patients not
      treated with steroid. Xenodiagnosis showed a clear increase in T. cruzi
      parasitemia, related to the corticosteroid dosage, without clinical
      manifestations during the study follow-up period.

PMID- 9148343
TI  - [Pharmacokinetics of lidocaine in obstetric patients after its epidural single
      dose administration].
AB  - OBJECTIVE: To determine the concentrations of lidocaine in maternal plasma and to
      establish the kinetic constants following absorption of a single dose of
      lidocaine in obstetric epidural anesthesia. PATIENTS AND METHOD: Epidural
      blockade was provided to 10 patients by a single injection of lidocaine at doses
      of 200 to 300 mg (265 +/- 35 mg). The plasma concentrations of lidocaine were
      determined 1, 5, 10, 15, 20, 40, 60, 120 and 180 min later and at the moment of
      birth, by way of polarized immunofluorescence (PIF) with a Tdx automatic analyzer
      (Abbott). RESULTS: Time until peak plasma concentration was 17.4 min. Peak
      concentrations ranged from 1.44 to 2.12 micrograms/ml. Plasma clearance took
      place at a rate of 10.1 +/- 1.7 ml/min/kg, more slowly than in surgical patients.
      Duration of anesthesia ranged from 40 to 80 min and was sufficient in all cases,
      even for women undergoing cesarean section. At birth (25 +/- 5 min after epidural
      injection), plasma concentration was 1.67 +/- 0.28 micrograms/ml. CONCLUSION:
      Injection of 200-300 mg of lidocaine provides good analgesia during childbirth,
      even when cesarean section is practiced, with no toxic effects for the mother.

PMID- 9148344
TI  - [On the 150th anniversary of the introduction of anesthesia in Spain: the role of
      dentists].
AB  - We first discuss the circumstances that were influential in the role played by
      dentists during the early stages of anesthesia. We then study the positions of
      several Spanish dentists on the new technique for eliminating pain. Two opposing
      groups are found: on the one hand physician-dentists were cautions and prudent,
      and on the other, professionals with lesser qualifications such as surgeon
      dentists, healers and bloodletters were clearly and boldly in favor of the new
      technique.

PMID- 9148345
TI  - [Anesthesia in lung transplantation].

PMID- 9148346
TI  - [Cardiocirculatory effects of halothane and isoflurane in respiratory distress
      caused by oleic acid].
AB  - INTRODUCTION: When lungs are damaged or affected by edema they behave differently
      from healthy lungs in the presence of drugs that can modify vascular reactivity.
      OBJECTIVES: To determine the effects of halothane and isoflurane on pulmonary
      edema induced by oleic acid in dogs. MATERIAL AND METHODS: Eighteen dogs were
      anesthetized with sodium pentothal. Hemodynamic and lung parameters as well as
      end-tidal gases were monitored. Pulmonary edema was induced with an injection of
      oleic acid (0.1 ml/kg). Five periods were studied: 1) before injection of oleic
      acid; 2) 90 min after injection; 3) 20 min after ventilation with 1 MAC halothane
      or isoflurane; 4) 20 min after 2 MAC ventilation with the assigned anesthetic,
      and 5) 20 min after withdrawal of anesthetic. RESULTS: With halothane, cardiac
      output and arterial blood pressure decreased significantly. With isoflurane,
      arterial pressure decreased by way of changes in vascular resistance. Neither
      anesthetic affected hypoxic pulmonary vasoconstriction. CONCLUSIONS: Neither
      anesthetic worsens arterial oxygenation in a model of pulmonary edema that is
      similar to adult respiratory distress.

PMID- 9148347
TI  - [Traumatic asphyxia and continuous venovenous hemofiltration. Report of a case].
AB  - A 32-year-old man was admitted with traumatic asphyxia, with aspiration to the
      bronchi after being buried under sand. The condition progressed to respiratory
      distress syndrome and systemic inflammatory response. Because ventilatory and
      hemodynamic deterioration was rapid and severe, in spite of mechanical
      ventilation and vasoactive drugs, we instated early continuous arteriovenous
      hemofiltration, which also allowed us to meet the patient's full nutritional
      needs. We believe that the patient's very satisfactory progress can be attributed
      to the early use of this procedure, along with appropriate specific treatment.

PMID- 9148348
TI  - [MUltiple sclerosis and obstetric epidural analgesia].
AB  - A prior diagnosis of multiple sclerosis (MS) has been considered a
      contraindication for performing epidural blocks due to the possible negative
      impact of the course of disease. For this reason, women with MS who given birth
      have rarely benefited from obstetric epidural analgesia. We report the case of a
      woman giving birth at full-term who had been diagnosed one year before the
      pregnancy of "probable" MS. She was given epidural analgesia with a mixture of
      bupivacaine and fentanyl at low doses. Both the birth and the immediate
      postpartum period transpired without complications and no new signs of disease
      were reported over the following years. We conclude that obstetric epidural
      analgesia with bupivacaine administered at a low concentration is safe for women
      with MS.

PMID- 9148349
TI  - [Efficacy of ondansetron in the prevention of nausea and vomiting after
      laparoscopic cholecystectomy].
AB  - To assess the efficacy of 4 mg of intravenous ondansetron versus placebo for the
      prevention of postoperative nausea and vomiting (PONV) in cholecystectomy, a type
      of surgery that is highly emetic. A random, double blind, placebo controlled
      study of 40 women over 18 years of age who were scheduled for non urgent
      laparoscopic cholecystectomy under general anesthesia. The patients were assigned
      to two groups to receive ondansetron (n = 23) or placebo (n = 17). Premedication
      and anesthesia were similar for all. The severity of PONV in the first 24 hours
      after surgery was recorded. There were no significant differences between the two
      groups with respect to biological characteristics or other factors that might
      influence the presentation or severity of PONV. The percentage of PONV-free
      patients was significantly higher in the ondansetron group than in the control
      group (73.91 and 11.76%, respectively; p < 0.001). Intravenous administration of
      4 mg ondansetron is significantly superior to placebo for PONV prophylaxis after
      laparoscopic cholecystectomy.

PMID- 9148350
TI  - [Severe airway obstruction in 4 cases of postoperative obstructive hematoma].
AB  - Obstructive hematoma is a rare postoperative complication of surgery on the floor
      of the mouth or the anterior region of the neck and throat. The insidious
      development of symptoms, including agitation, which may be attributed to other
      causes, or their late appearance in hospital wards staffed by personnel
      unaccustomed to treating airway complications, means that the risk of hypoxia or
      respiratory failure is high. We describe four patients in whom the clinical
      picture began with agitation and dyspnea. Once the diagnosis was established, and
      after decompression of the surgical wound, tracheal intubation proved impossible
      in two patients, who required emergency tracheostomy. Two patients died from lack
      oxygen. Our review of the literature and experience have led to the following
      recommendations that may prevent avoidable deaths: a) the caregivers directly
      responsible for these patients should receive specific training; b) long-term
      monitoring and observation should take place in recovery units where early signs
      and symptoms can be detected and treated immediately; c) tracheostomy or 24-hour
      intubation should be considered when surgery in this anatomic region is highly
      invasive; d) consider that postoperative agitation in these patients is a symptom
      of hypoxia unless another cause is demonstrated; and e) the zone must be
      decompressed rapidly by opening the surgical wound and safeguarding the airway
      whenever obstructive hematomas present.

PMID- 9148351
TI  - [Intraperitoneal insufflation of CO2 and body temperature].

PMID- 9148352
TI  - [The Spanish edition of "Educational Synopsis in Anesthesia." The 1st electronic
      anesthesiology periodical].

PMID- 9148353
TI  - [Hearing loss after spinal anesthesia].

PMID- 9148354
TI  - [Consequences and prevention of mild intraoperative hypothermia].

PMID- 9148355
TI  - [Air-convection heater for abdominal surgery. Study of the relation between
      surgical time and the efficacy of body temperature maintenance].
AB  - OBJECTIVES: 1) To quantify the efficacy of forced air warming for maintaining
      body temperature during general anesthesia of adults, and 2) to study the
      relation between the duration of surgery and the level of thermal protection
      provided by the device used. PATIENTS AND METHODS: We studied 30 adult patients
      of both sexes who were scheduled for abdominal surgery involving laparotomy.
      After three patients were excluded because surgery was unfeasible, the remaining
      27 were allocated randomly to a control group (n = 14) or a group (n = 13) to be
      warmed by a Bair Hugger (Augustine Medical Inc.) heater. Esophageal temperature
      was checked every 30 min by one probe of a modular thermometric channel (Mon-a
      therm) 6510 Mallincrodt, while ambient temperature was monitored by the second
      probe. RESULTS: Significant differences in esophageal temperature were observed
      between the two groups from the second hour after start of surgery, and the
      differences increased over time. Differences were observed at the end of surgery
      (Bair group: 36.4 +/- 0.5 degrees C; control group: 34.7 +/- 1.1 degrees C) and
      upon admission to the intensive care recovery unit (Biar group: 36.3 +/- 0.6
      degrees C; control 34.8 +/- 1.0 degrees C) (p < 0.0001). CONCLUSIONS: The Bair
      Hugger heater is effective during abdominal operations lasting two or more hours.
      The device not only prevented hypothermia from deepening during surgery, but also
      reversed hypothermia in spite of being used after anesthetic induction and in
      spite of the loss of heat produced by secondary vasodilation.

PMID- 9148356
TI  - [Changes in the concentrations of catecholamines and cortisol in balanced
      anesthesia and total intravenous anesthesia].
AB  - OBJECTIVE: To compare hormone response to stress caused by surgery performed
      under balanced general anesthesia and total intravenous anesthesia. PATIENTS AND
      METHOD: Two randomly formed groups of 24 patients each were studied. All patients
      were scheduled for lumbar laminectomy to correct disc hernias, with one group
      receiving balanced anesthesia with isoflurane (expiratory fraction between 0.5%
      and 0.6%), and the second group receiving total intravenous anesthesia (TIVA)
      (propofol infusion changed every 10 min from 12 to 6 mg/kg/h). Analgesics and
      relaxants were given by continuous infusion at preestablished doses (fentanyl 2
      micrograms/kg/h; vecuronium 0.05 mg/kg/h). Cortisol and catecholamine (adrenalin,
      noradrenaline and dopamine) levels were determined at the following times: the
      morning of surgery (baseline), 5 min after intubation, 5 min after incision, 30
      and 60 min after intubation; 5 min after tube removal and upon admission to the
      recovery unit. RESULTS: Cortisol levels decreased from baseline (14 +/- 3 pg/ml)
      until 30 min after intubation (4 +/- 2 pg/ml; p < 0.05) in the balanced
      anesthesia group. Adrenaline levels followed the same pattern (baseline 77 +/- 7
      versus 57 +/- 10 pg/ml 30 min after intubation). Dopamine levels were
      statistically different (p < 0.05) at baseline (42 +/- 3 pg/ml), after intubation
      (38 +/- 2 pg/ml) and after incision (35 +/- 3 pg/ml), but the difference
      disappeared 30 minutes after intubation (38 +/- 8 pg/ml). Noradrenaline levels
      after incision (425 +/- 116 pg/ml) were significantly different from those at
      baseline (671 +/- 124 pg/ml), and the difference was evident until 60 min after
      incision. In the TIVA group we found significantly higher cortisol levels after
      intubation (21 +/- 0 pg/ml) than after baseline (14 +/- 2 pg/ml); this level
      decreased after extubation (7 +/- 0 pg/ml; p < 0.05). Adrenaline levels were
      significantly higher than at baseline (64 +/- 11 pg/ml) at times corresponding to
      intubation (76 +/- 5 pg/ml) and extubation (48 +/- 5 pg/ml). Noradrenaline
      increased significantly over baseline (497 +/- 99 pg/ml) after incision (597 +/-
      90 pg/ml) and decreased significantly after 30 min. The increases in cortisol
      were significantly greater in the TIVA group than in the control group after
      intubation (21 +/- 0 versus 8 +/- 3 pg/ml, respectively) after intubation, after
      incision (18 +/- 2 versus 6 +/- 3 pg/ml) and 30 minutes after intubation (15 +/-
      2 versus 4 +/- 2 pg/ml). Similar differences were found for dopamine after
      intubation (49 +/- 2 versus 38 +/- 2 pg/ml) and after incision (45 +/- 5 versus
      35 +/- 3 pg/ml). CONCLUSIONS: Hormone levels are significantly higher during
      intravenous anesthesia than during balanced anesthesia, and the difference is
      evident from the earliest measurement performed.

PMID- 9148357
TI  - [Electron microscopy of the lesions produced in the human dura mater by Quincke
      beveled and Whitacre needles].
AB  - INTRODUCTION: Comparisons of Quincke needles and non traumatic "pencil point"
      needles in recent years have reported lower rates of post dural puncture headache
      using the later type. Our new understanding of the morphology of the human dura
      mater motivated us to study dural lesions caused by the Whitacre 25 G and Quincke
      26 G needles, using scanning electron microscopy with the aim of determining
      whether there is an anatomic basis for the different outcomes. METHOD: The dura
      mater from three fresh cadavers of individuals aged 65, 70 and 72 years were
      punctured 40 times at an angle of 90 degrees each time. The Whitacre 25 G needle
      was used for 20 punctures and the Quincke 26 G needle was used for the other 20.
      Half the punctures were performed with the bevel in the parallel alignment and
      the other half with the bevel perpendicular to the spinal column. Fifteen min
      after causing the punctures, specimens were fixed in solutions of glutaraldehyde
      phosphate buffer and dehydrated in acetone. After critical point removal of the
      acetone, after the specimens were treated with carbon and metallized with gold.
      The lesions were examined externally and internally and expressed as the ratio of
      area of lesion to diameter of the needle that had caused them. RESULTS: Whitacre
      needle: each lesion consisted in the superimposition of multiple damaged layers
      that started to close individually. After 15 min the outermost layers were 90%
      closed and the innermost ones had closed entirely. Layers in the arachnoid
      surface of the dura mater had closed from 86 to 88%, while deeper layers in the
      thick part had closed 97 to 98%. Quincke needle: lesions were V-shaped or half
      moon shaped, much like the opening formed by a can opener, on both the external
      and internal surfaces. Alignment of the bevel of the needle parallel to the
      spinal column did not lead to a different shape of puncture. After 15 min the
      lesions had closed 94 to 95% on the epidural surface and 95 to 96% on the
      arachnoid side, a difference attributable to the retraction of the arachnoid
      layers over the spinal column. CONCLUSION: Non traumatic beveled dural needles,
      termed "pencil point needles", only partially separate dural fibers, and lesions
      caused by these needles develop in a more complex way. The Quincke 26G needle
      produced a puncture that is morphologically different from that caused by the
      Whitacre 25G needle, although lesions produced by both types close more than 94%
      after 15 min. We believe the size of the lesion caused by these needles does not
      explain the difference in post dural puncture headache due to loss of spinal
      fluid.

PMID- 9148358
TI  - [Intraoperative anesthetic management of kidney failure in adult liver
      transplantation. Conventional hemodialysis].
AB  - OBJECTIVE: To evaluate our application of indications, use and benefits of
      conventional hemodialysis during surgery in patients with advanced liver disease
      and acute or chronic renal failure undergoing liver transplantation (LP), liver
      retransplantation (LRT) or combined hepatorenal transplantation (CHRT). PATIENTS
      AND METHODS: We retrospectively reviewed the cases of 22 patients with advanced
      liver disease, 11 with acute renal failure and 11 with chronic renal failure. We
      performed 6 LT, 5 LRT and 11 CHRT. The following data were recorded in the
      periods before, during and immediately after surgery: metabolic, hemodynamic and
      coagulation parameters; bicarbonate, calcium and inotropic drug requirements;
      incidences during reperfusion of the graft; surgical technique used; and
      survival. RESULTS: Seven patients (32%) needed hemodialysis, 4 (18%) needed
      ultrafiltration, 7 (32%) needed both and 4 (18%) required neither. For 6 patients
      total clamping of the inferior vena cava (ICV) was required with external
      venovenous bypass. For 8 patients total clamping of the IVC was performed without
      venovenous bypass. For 8 others IVC clamping was partial with retrohepatic
      preservation (piggy-back). There were 2 deaths during surgery, 4 more within the
      first month after surgery and 4 more in the second month. Overall survival was
      36.4% among acute patients and 72.7% among CHRT patients. CONCLUSIONS: 1)
      Conventional hemodialysis during surgery is feasible and gives good results; 2)
      conventional "high efficiency" hemodialysis is more effective and useful in these
      patients than is either slow, continuous hemodialysis or filtration; 3) the
      survival rate of CHRT patients is similar to that of patients undergoing LT with
      normal kidney function, and 4) partial IVC clamping in the anhepatic phase may
      decrease the need for ultrafiltration.

PMID- 9148359
TI  - [Low molecular weight heparins. Implications in anesthesia and resuscitation].
AB  - Low molecular weight heparins are a group of drugs that have only recently been
      introduced in clinical practice. The are widely used for prophylaxis in
      thromboembolic disease and are being employed increasingly to treat established
      venous thrombosis. One way in which these drugs are often used is for prophylaxis
      in the perioperative period for patients at high risk of developing venous
      thromboembolism, and the anesthesiologist must therefore be familiar with the
      main aspects of this application. We review pharmacological characteristics of
      these drugs as well as the literature on low molecular weight heparins, stressing
      points of main interest to the anesthesiologist and intensive care recovery unit
      specialist, namely adverse effects (mainly bleeding) and the implications that
      use of low molecular weight heparin will have on choice of anesthetic (in
      particular the dilemma of whether to use local/regional anesthesia).

PMID- 9148360
TI  - [Indication for spinal anesthesia for cesarean section in HELLP syndrome
      coagulopathy].
AB  - We describe the relation between coagulation and local-regional anesthesia in two
      women with HELLP syndrome who required emergency cesarean delivery. HELLP
      syndrome involves hemolysis, elevated liver enzyme levels and thrombopenia
      complicating the hypertension of pregnancy. Regional anesthesia presents
      advantages for mother and fetus in this context but also involves the risk of
      coagulopathy. In the first case we describe, coagulation was normal before
      surgery and epidural anesthesia was therefore prescribed. The initial epidural
      puncture was hemorrhagic and a second, higher puncture was made to insert the
      catheter. Shortly after surgery severe thrombopenia developed and lasted 24
      hours; formation of an epidural hematoma caused by vascular lesion during
      puncture was suspected. The epidural catheter was left in place, and the patient
      was kept under observation and seen by a neurologist within the first 48 hours.
      Outcome was good. In the second patient, epidural puncture was contraindicated by
      the presence of preoperative coagulopathy, and the cesarean was performed without
      complications under intradural anesthesia provided with low doses of bupivacaine
      and fentanyl. The coagulopathy that accompanies HELLP syndrome should be assessed
      not only before taking the decision on anesthetic technique; as the condition can
      be progressive it can become most severe after the epidural puncture is
      performed, as shown by the first case we describe. The patient's condition must
      be watched closely until coagulation becomes normal. Removal of the epidural
      catheter must wait until coagulopathy is resolved. When coagulopathy is evident
      before surgery, intradural anesthesia is a safe option provided hemodynamic
      stability is assured, as demonstrated by the second case we report.

PMID- 9148361
TI  - [Postoperative respiratory alkalosis as a complication of neuroendoscopy].
AB  - Endoscopic neurosurgery is a minimally invasive technique that has been
      developing rapidly. It is mainly indicated for the treatment of hydrocephaly due
      to ventriculocisternostomy, biopsies of cerebral ventricular lesions, evacuation
      of cerebral hematomas and spinal surgery. Hemorrhage, infection and spinal fluid
      fistula are known complications. We report the appearance of symptomatic
      postoperative respiratory alkalosis in a patient who underwent
      ventriculocisternostomy by endoscopic neurosurgery. The underlying disease was
      obstructive hydrocephaly secondary to partial stenosis of the Silvius aqueduct.

PMID- 9148362
TI  - [Subarachnoid hemorrhage and electrocardiographic changes. Is it or is it not a
      sign of myocardial ischemia?].

PMID- 9148363
TI  - [Acute postoperative pancreatitis, is it associated with the use of
      ondansetron?].

PMID- 9148364
TI  - [Continuous axillary plexus block in pediatrics].

PMID- 9148366
TI  - [Aspiration pneumonia during cesarean section].

PMID- 9148365
TI  - [Use of low molecular weight heparins].

PMID- 9148367
TI  - [Alternative medicine. State of the art and perspectives].

PMID- 9148369
TI  - Serum interleukin-6 in acute pancreatitis due to common bile duct stones. A
      reliable marker of necrosis.
AB  - In a prospective clinical study we have assessed the value of serum interleukin-6
      in comparison with C-reactive protein in discriminating necrotizing from
      oedematous acute pancreatitis due to common bile duct stones in the first hours
      of disease. The study comprised 36 patients with acute biliary pancreatitis;
      inclusion criteria were admission in hospital within 48 hours from the onset of
      symptoms, availability of contrast enhanced CT scan within 72 hours from
      admission and presence of common bile duct stones at early ERCP. A sample of
      serum was taken at hospitalization and interleukin-6 and C-reactive protein were
      measured. Interleukin-6 levels were significantly higher in necrotizing
      pancreatitis, being closely related to the extension of necrosis. C-reactive
      protein showed low efficacy in detecting necrotizing forms, although its levels
      were higher than in oedematous. We conclude that serum interleukin-6 is a very
      reliable marker of necrosis in the first 48 hours of acute biliary pancreatitis.

PMID- 9148368
TI  - [Urinary tract infections: risk factors and therapeutic trends].
AB  - Urinary tract infections (UTIs) are very common in medical practice. Women have a
      high prevalence of UTIs, approximately 50 times higher than men. A large
      proportion of this prevalence is probably caused by anatomic and physical factors
      Chemical analysis of urine composition, examination of the urinary sediment and
      the bacterial colony counts are of great value for diagnosis and therapy. The
      patients may be benefit from antibiotic doses. In addition to
      trimethoprimsulfamethoxazole (TMP/SMZ), amoxicillin and cephalosporins, the
      authors observed a new drug: fluoroquinolones. These drugs derived by nalidixic
      acid and included: ciprofloxacin, enoxacin, lomefloxacin, norfloxacin, pefloxacin
      and rufloxacin. They are sinergistic against most Gram positives and negatives
      including Pseudomonas aeruginosa and Proteus mirabilis. Fluoroquinolone is an
      antibacterial agent that is effective in treating urinary tract infections. It is
      usually administered orally and is well absorbed after oral ingestion. Quinolones
      are preferable to TMP/SMZ because of their greater antibacterial activity that
      occurred in about 82% of women. A dose of quinolones (400 mg daily for 3 days)
      has been particularly effective in the treatment of UTIs. The amoxicillin
      clavulanic acid can be used for treatment even if increased antibiotic
      resistance. The efficacy, relative safety and low cost of quinolones predispose
      to utilize its like the first treatment choice.

PMID- 9148370
TI  - [Serum variations of 2 markers of fibrogenesis in chronic hepatitis C treated
      with alpha interferon].
AB  - We evaluated variations in serum levels of N-terminal peptide of type III
      procollagen (PIIIP) and laminin (Lam-P1) in 36 anti-HCV positive patients,
      confirmed by RIBA II, with chronic hepatitis treated with alpha interferon (IFN)
      at a dose of 6 million units (MU) three times for week for 6 months, followed by
      3 MU three times for week for a further 6 months. We consider responders (R)
      those patients who after one year of therapy had normalized ALT levels, and non
      responders (NR) the remaining subjects. Serum PIIIP and Lam-P1 were determined by
      RIA on entry to the study and at 12 months. Ten patients underwent a percutaneous
      liver biopsy also at the end of the therapy for the histological evaluation of
      the necroinflammatory activity and fibrosis according to the Knodell score
      system. Overall, at the end of therapy, the mean levels of both markers were
      lower than at entry to the study, with a statistically significance only for the
      Lam-P1 values (p < 0.05). When, however, we divided the patients into R (n = 15)
      and NR (n = 21) subgroups, the mean baseline values of both markers were
      significantly higher in NR vs controls and after therapy there was a
      significantly reduction only for PIIIP values (p < 0.01). In the group of R there
      is a slight, but not significantly reduction of both markers. The comparison of
      the Knodell's score before and after IFN treatment showed an improvement of the
      necroinflammatory activity, but not of fibrosis. In conclusion patients R to IFN
      therapy have lower baseline values of PIIIP and Lam-P1 than NR and therapy with
      IFN improves the serum values of PIIIP as well as the score of the
      necroinflammatory activity.

PMID- 9148371
TI  - [Drug-resistant epilepsy treated with ketogenic diet].
AB  - A 4-year old girl affected by intractable seizures was treated with ketogenic
      diet. The diet was calculated to provide appropriate protein intake for growth
      (1.4 g/kg body weight) and adequate calories (1600 kcal) derived from 4 parts fat
      and 1 part protein + carbohydrates. The child remained on the diet for 8 months
      and had a decrease in seizure frequency of 90%. No serious side effects were
      reported and it was possible to discontinue or decrease antiepileptic drugs. Our
      results confirm the efficacy of ketogenic diet in the treatment of epilepsy.
      Since it is known that 20 to 30% of all patients with epilepsy do not have their
      seizures completely controlled with established antiepileptic drugs, it would be
      useful to increase the application of this dietetic treatment in selected
      patients in Italy as it already happens in other countries.

PMID- 9148372
TI  - [Painful myoedema caused by rhabdomyolysis: a proposal of a new integrated
      therapeutic treatment].

PMID- 9148373
TI  - [Analysis of lymphocyte-T receptor in autoimmune diseases].

PMID- 9148374
TI  - [Liver transplantation. Selection criteria and risk evaluation].
AB  - The significant advances achieved in the last years in the field of liver
      transplantation have led to an almost routinely performance of this therapeutic
      approach throughout North America and Western Europe. This has led to an
      increased demand so that today the real problem is the organ availability and the
      need to use those supplied only for patients with best chances of success. For
      this reason timing of the operation and patient selection are of critical
      importance. The ultimate success depends on better surgical procedures and
      advances in immunosuppressive therapy, but perhaps even more on an accurate
      patient evaluation. The patient selection is based on standardized medical
      criteria which constitute the indication in patients with end-stage liver disease
      and on a careful search for risk factors. To this purpose the evaluation of the
      tolerance of the hemodinamic stress during clamping of the inferior vena cava is
      of critical importance and must be carefully evaluated both in patients with
      known and unknown coronary disease. Another condition to be considered is lung
      hypertension which is frequently associated with portal hypertension. Finally,
      important conditions for a good evaluation are the epatopulmonary syndrome and
      diabetes. The last condition is not a contraindication unless associated with
      severe vascular, cardiac or renal complications.

PMID- 9148375
TI  - [The L-arginine-nitric oxide system: physiology, physiopathology and clinical
      relevance].
AB  - In this review we describe what is known about nitric oxide (NO), focusing on its
      clinical significance. It is now well appreciated that NO is a pivotal endogenous
      messenger molecule in a variety of physiological and pathophysiological
      processes. In the cardiovascular system NO participates in the paracrine
      regulation of vascular tone, body fluid homeostasis and platelet aggregation and
      adhesion. In the nervous system NO is a neurotransmitter that underpins several
      functions, including the formation of memory. In addition, NO is produced in
      large quantities during host defense and immunologic reactions. Perturbation in
      NO bioactivity has been shown to represent an important pathophysiologic
      mechanism underlying a number of disease states, such as atherosclerosis,
      hypertension, diabetes mellitus, and septic shock.

PMID- 9148376
TI  - The relationship between glucose control and the development of diabetic
      nephropathy in type I diabetes.
AB  - Diabetic nephropathy is a major cause of morbidity and mortality in patients with
      diabetes and occurs in about one-third of such patients. The course of
      nephropathy has become better defined, with patients initially developing
      microalbuminuria (albumin excretion rates [AER] between 20 and 200
      micrograms/min), then overt nephropathy (AER > or = 200 micrograms/min) and
      finally a decline in GFR eventuating in end-stage renal disease (ESRD). Although
      metabolic control has long been hypothesized as a contributor to the development
      of nephropathy, it is only in recent years that this hypothesis has been proven.
      A number of observational studies have shown correlations between glycemic
      control and the development of various levels of albuminuria and also declines in
      GFR. Several small, prospective, randomized, interventional studies and the
      Diabetes Control and Complications Trial (DCCT) have now definitely proven that
      improved metabolic control that achieves near-normoglycemia can significantly
      decrease the development and progression of early nephropathy as well as other
      long-term complications of diabetes, including retinopathy and neuropathy. It is
      now conceivable that the achievement of near-normoglycemia plus the addition of
      angiotensin-converting enzyme inhibitors if microalbuminuria develops may greatly
      decrease the numbers of patients eventually requiring renal replacement therapy.

PMID- 9148377
TI  - Therapeutic interventions for nephropathy in type I diabetes mellitus.
AB  - Diabetic nephropathy is the single most common cause of end-stage renal disease
      in the United States. Recently, several major therapeutic interventions have been
      developed and shown to slow or halt the progression of renal failure in patients
      with diabetes and diabetic kidney disease. Studies have shown that in patients
      with insulin-dependent diabetes and proteinuria, lowering systemic blood pressure
      slows the rate of decline in renal function and improves patients' survival. In
      the recently completed trial of angiotensin converting enzyme (ACE) inhibition in
      diabetic nephropathy, ACE inhibitors were specifically shown to decrease
      dramatically the risk of doubling of serum creatinine or reaching a combined
      outcome of end-stage renal disease or death independent of their effect on
      systemic blood pressure. In studies with small numbers of patients, dietary
      protein restriction has also been shown to slow the rate of decline of renal
      function. New potential interventions currently undergoing study include
      treatment with aldose reductase inhibitors, treatment with inhibitors of the
      formation of advanced glycosylation end-products, treatment of dyslipidemia, and
      a variety of other less well-studied interventions.

PMID- 9148378
TI  - Clinical and pathological course of renal disease in non-insulin-dependent
      diabetes mellitus: the Pima Indian experience.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) and the renal disease
      attributable to it have been characterized extensively in the Pima Indians, a
      group of American Indians who form the Gila River Indian Community in Arizona.
      Both of these diseases are common in this community, and their onset and duration
      are known with greater certainty than in other populations because research
      examinations, which include oral glucose tolerance tests and measures of urinary
      protein excretion, have been performed frequently on most members of the
      population for the past 30 years. Studies of glomerular structure and hemodynamic
      function in diabetic Pima Indians indicate that glomerular hyperfiltration often
      develops at the onset of NIDDM and remains elevated until after overt nephropathy
      appears. Structurally, the glomeruli in subjects with microalbuminuria are not
      clearly distinguishable from those in subjects with normoalbuminuria, but
      macroalbuminuria is characterized by extensive glomerular sclerosis, mesangial
      expansion, and widening of epithelial cell foot processes that together lead to a
      rapid decline in the glomerular filtration rate. The decline in glomerular
      function in subjects with macroalbuminuria is due both to a loss of
      ultrafiltration surface area and to reduction in glomerular hydraulic
      permeability.

PMID- 9148379
TI  - Type II diabetic nephropathy: its clinical course and therapeutic implications.
AB  - Type II diabetes is responsible for more end-stage renal disease in the United
      States than any other single condition. Until recently, the majority of research
      in diabetic nephropathy has focused on patients with type I diabetes despite the
      fact that type II nephropathy is a more prevalent condition. The notion that
      there are major differences between the nephropathy of these two types of
      diabetes is not supported by recent literature. The biggest difference appears to
      be related to ethnic risk. Histopathologic differences are now being described as
      well. Clinical interventional trials are few compared to type I diabetes;
      however, it seems that maneuvers that improve renal prognosis in patients with
      type I diabetes (blood pressure control, blood glucose control, and the use of
      angiotensin-converting enzyme inhibitors) apply to the type II population as
      well. Some of the calcium channel blockers lower proteinuria to a degree that
      suggests renoprotection and may further improve outcome.

PMID- 9148380
TI  - Biochemical events and cytokine interactions linking glucose metabolism to the
      development of diabetic nephropathy.
AB  - The important role of hyperglycemia in the genesis of diabetic renal disease has
      been strengthened by tissue culture studies, experimental animal models, and
      clinical trials. A mechanistic understanding of the cellular and biochemical
      processes that link hyperglycemia with the development of diabetic nephropathy is
      indispensable for directing the most optimal therapeutic interventions. Likely
      mediators of the effects of high ambient glucose include activation of the polyol
      pathway, increased protein kinase C activity, nonenzymatic glycation of
      circulating or matrix proteins, and/or aberrant synthesis or actions of cytokines
      and vasomodulatory agents. The latter include angiotensin II, thromboxane,
      platelet-derived growth factor, endothelins, insulin-like growth factor-1, and
      transforming growth factor-beta. The studies we review here argue strongly in
      support of the hypothesis that elevated production and/or activity of
      transforming growth factor-beta in the kidney is a final common mediator of
      diabetic renal hypertrophy and mesangial matrix expansion.

PMID- 9148381
TI  - The renal hemodynamic basis of diabetic nephropathy.
AB  - Diabetic nephropathy occurs in approximately one third of individuals with
      insulin-dependent diabetes mellitus (IDDM), recent studies suggest that a similar
      proportion of non-insulin-dependent diabetes mellitus (NIDDM) patients develop
      this serious complication as well. Of the many risk factors identified in the
      pathogenesis of nephropathy, hemodynamic alterations have been particularly well
      studied. Increases in glomerular filtration rate (GFR), largely driven by
      increases in plasma flow and glomerular capillary pressure, are apparent in early
      IDDM and NIDDM. Furthermore, the elevation in capillary pressure may be damaging
      to glomerular endothelial, epithelial and mesangial cells, thereby initiating and
      contributing to the progression of diabetic nephropathy. Numerous mediators of
      diabetic hyperfiltration have been proposed, and this phenomenon likely reflects
      a mutilfactorial etiology. The purpose of this article is to examine the
      hemodynamic alterations characteristic of diabetic nephropathy, their etiology,
      and their role in the development and progression of diabetic nephropathy.

PMID- 9148382
TI  - [Introductory thoughts on the special issue "Transplantation"].

PMID- 9148383
TI  - [Logistics characteristics and surgical aspects of heart transplantation].
AB  - Orthotopic cardiac transplantation is an established treatment for terminal
      cardiac diseases. The organization of the operation closely depends on the
      successful team work between cardiologists, selecting the proper patients for
      this procedure, the anesthesiologists taking care of the multiorgan donor and the
      cardiac surgeons managing in parallel the donor and the recipient. Accurate donor
      evaluation and treatment are essential for a perfect graft function immediately
      after transplantation. Orthotopic heart transplantation can also be offered as a
      therapeutical option in adolescents presenting with end-stage heart failure due
      to complex congenital heart disease and who have sustained multiple previous
      operations. In this paper, some special logistic and technical particularities of
      cardiac transplantation are presented and discussed.

PMID- 9148384
TI  - [Follow-up after heart transplantation].
AB  - The prognosis of patients with end-stage cardiac disease has dramatically changed
      with transplantation. The incidence of complications remains relatively high and
      needs a very careful follow-up to have good long term results.

PMID- 9148385
TI  - [Lung transplantation].
AB  - Over the last years lung-transplantation has evolved into an effective therapy
      for patients with end-stage disease pulmonary parenchyma or vessels. The main
      indications for lung-transplantation are pulmonary emphysema, cystic fibrosis,
      idiopathic pulmonary fibrosis or pulmonary hypertension. All diseases associated
      with chronic infections such as cystic fibrosis or bilateral bronchiectasis need
      a bilateral lung-transplantation. In addition we transplant bilaterally all
      patients with pulmonary hypertension and young patients with pulmonary emphysema.
      In all other cases, a unilateral lung-transplantation is the treatment of choice.
      Heart-lung-transplantation is generally applied in patients with Eisenmenger
      syndrome. At the time of transplantation patients suffer from dyspnea NY-HA III
      IV and are mostly oxygen dependent. Life expectancy is limited to 6 to 18 months.
      Over the last years nearly 5000 lung-transplantations were performed worldwide.
      Survival rate after 1 year was 70 to 90% and 60 to 70% after 3 years
      respectively. In Switzerland there were approximately 80 lung-transplants
      performed since 1992 with a one year survival rate of approximately 75%.

PMID- 9148386
TI  - [Homograft in the therapy of cardiovascular diseases].
AB  - Despite considerable progress in prosthetic valve technology, there is actually
      no ideal artificial heart valve that may be employed in all circumstances, when
      replacement of a diseased aortic valve is necessary. The choice for optimal valve
      substitute includes mechanical prosthesis, bioprosthetic xenografts, homografts
      and pulmonary autografts. More recently an aortic valve sparing operation has
      been proposed in younger patients presenting with anulo-aortic ectasia. The use
      of homograft heart valves has now been widely accepted in the treatment of
      congenital heart defects, as well as for an increasing number of valvular
      pathologies, especially in infective endocarditis. Heart valve preservation by
      cryopreservation techniques helps to store the small amount of donor material for
      special indications without loss of quality, thus permitting elective surgery. In
      vascular surgery, some concern persists regarding the use of prosthetic material
      for the treatment of mycotic aneurysms and graft infection. In situ repair with a
      new vascular prosthesis and resection followed by extra-anatomic reconstruction
      carry a high peri-operative mortality and substantial morbidity. Cryopreserved
      vascular homografts represent a valuable alternative in these challenging
      situations.

PMID- 9148387
TI  - [What is your diagnosis? Traumatic transsection (incomplete, non-transmural
      aortic rupture) of the thoracic aorta with post-traumatic aneurysm of the
      proximal descending aorta].

PMID- 9148388
TI  - [Emergencies in neurological patients].
AB  - Patients with neurological diseases amount to about one fifth of hospital
      admissions. Out of the numerous emergency situations three leading presentations
      are discussed. In an isolated epileptic grand mal seizure immediate treatment is
      not needed, whereas the different forms of status epilepticus ask for emergency
      measures. Acute headache may be a sign of subarachnoid hemorrhage or an other
      dangerous intracranial affection. Several harmless forms of acute headache are
      discussed. Central paLsies with acute presentation are most often of
      cerebrovascular origin. Peripheral palsies including Bell's palsy are discussed.

PMID- 9148389
TI  - [Acute lumbar disk displacement with nerve root compression. Indications for
      peridural steroid injection].
AB  - The rationale and indication, but also the efficacy and limitation of lumbar
      epidural corticosteroid injection in patients suffering from acute lumbosacral
      radicular pain are explained. Epidural administration of corticosteroids with
      longterm effect and bupivacaine by a translumbar approach in patients suffering
      from acute low back pain and sciatica causes an immediate, persistent pain relief
      and a more prompt regression of nerve root compression compared to patients just
      treated by bed rest and analgesics. The state of the art is based on recent meta
      analyses and the understanding of the pathophysiology of discal hernia which
      includes inflammation. Contemporary concepts and data from recent reviews are
      summarized to elucidate current recommendations and suggestions for the
      management of patients with acute sciatica. The postulate of an application
      performed by an experienced anaesthesiologist is stressed. Advantages of this
      invasive form of therapy include reduction of addictive analgesic drugs,
      decreased time of absolute immobilisation, respectively strict bed rest, and of
      hospitalisation.

PMID- 9148390
TI  - [Emergencies in oncology].
AB  - Emergencies in oncologic patients are common and diverse. Almost every cancer
      patient will develop at least one emergency situation at the beginning or in the
      further course of his disease. The cancer itself or cancer treatment typically
      give rise to otherwise rare emergency development. In this review detailed
      descriptions of spatial cord compression syndrome, superior vena cava obstruction
      as well as hypercalcemia are given. Finally problems due to cerebral metastases,
      pulmonary embolism, hyperviscosity and hyperuricemia are briefly summarized.

PMID- 9148391
TI  - [Hematological emergencies].
AB  - In this short review some important hematologic emergencies, that have been
      discussed at a round table on the occasion of the 22, meeting of internal
      medicine in central Switzerland are outlined without intention to be complete.
      The following emergencies are featured: Anemia, increased hematocrit
      (polyglobulia), severe (unexpected) neutropenia, marked hyperleukocytosis and
      leukemias, severe thrombocytopenia; thrombocytopathies (hereditary or acquired),
      von Willebrand-disease, acquired or hereditary coagulation disorders
      (coagulopathies), acute venous thrombosis; acute hemolytic transfusion reaction,
      posttransfusion purpura, severe autoimmune hemolysis.

PMID- 9148392
TI  - [Diabetic emergencies].
AB  - Based on case reports pathogenesis and treatment of the following diabetic
      emergencies were discussed: 1. The hyperosmolar non-ketotic coma without or with
      only modest ketosis occurring mainly in type II diabetics and the severe
      ketoacidosis with or without disturbed consciousness occurring mainly in type I
      diabetics are the two forms of severe metabolic decompensation of diabetes
      mellitus. 2. Severe hypoglycaemia may be caused by treatment with sulfonylureas
      and insulin. 3. The most dangerous life threatening adverse effect of biguanides
      is lactic acidosis. The incidence of ketoacidosis is about 1-5% in type I
      diabetics with a mortality of 3-9%. Mortality rates of hyperosmolar non-ketotic
      comas are much higher, approaching 20-40%, and are explained by severe
      concomitant complications and older age. The most important triggering factors of
      diabetic coma are infections, insulin dispensing errors and non-compliance.
      Carefully instructing patients about the risks of loosing appetite and vomiting
      as early signs of ketoacidosis is essential. Adequate replacement of fluid,
      electrolyte and water are the most important therapeutical aspects of
      ketoacidosis and hyperosmolar non-ketotic coma. Early diagnosis and appropriate
      treatment of infection by antibiotics are important. Complication of therapy
      (hypokalemia, hypovolemia and rapid full of oncotic pressure) should be avoided
      by clinical and laboratory monitoring. Treatment of acidosis with bicarbonate has
      been found more dangerous than useful. Severe hypoglycaemia is the most important
      and most dangerous side effect of sulfonylurea and insulin. The incidence of
      severe hypoglycaemia under glibenclamide ist 3-5 fold higher than under treatment
      with tolbutamide or glibornurid. Glibenclamide should not be recommended anymore.
      Longterm experience of the therapeutic security of new sulfonylurea derivates
      like glimepirid is lacking. Blood-glucose-measurements in the afternoon are
      important for recognizing disposition to sulfonylurea hypoglycaemia, because at
      this time the blood-glucose-values tend to be lower than in the morning fasting
      state. Under insulin treatment the following risk factors for severe
      hypoglycaemia need to be considered: metabolic control in the near normal range,
      intensified treatment with rapidly decreasing HbA1c-levels, impaired renal
      function, unawareness o hypoglycaemia. When the renal function is impaired,
      biguanide treatment is not indicated because of the risk of lactic acidosis. Most
      of the diabetic emergency situations are avoidable by proper education of the
      patients.

PMID- 9148393
TI  - [Severe allergic-immunologic reactions].
AB  - Besides acute bronchial asthma IgE-mediated anaphylaxis is certainly the most
      important allergological emergency. Anaphylaxis is most often caused by drugs,
      foods and insect stings. The most relevant pathogenetic factors induced by
      allergy mediators are hypovolemia, bronchial obstruction and cardiac failure.
      Emergency treatment consists in intramuscular application of adrenaline and
      volume substitution by intravenous infusion. All patients should be hospitalized
      immediately and treated on an intensive care unit. Unfortunately, the subsequent
      consultation with an allergist does often not take place. This important
      preventive measure includes supply of instruction for allergen avoidance and of
      emergency medications. In anaphylaxis induced by insect stings specific
      immunotherapy should be started.

PMID- 9148394
TI  - [Right-side neck pain].

PMID- 9148395
TI  - [Recurrent infections of the upper airways].

PMID- 9148397
TI  - [How risky is lung resection today?--perioperative morbidity and mortality in
      open thorax surgery].
AB  - We retrospectively analyzed hospital morbidity and mortality following primary
      open lung surgery from August 1990 to December 1994 in 187 consecutive patients.
      180 pulmonary resections and 7 exploratory thoracotomies were performed in 141
      men and 46 women, with mean age 60.4 +/- 11.9 years. 142 patients were aged < 70
      years (median 58.5), and 45 (25%) > 70 years (median 73). Tumor stage as well as
      preoperative ASA classification and FEV1 were similar in these age groups. No
      difference could be found in hospital morbidity of elderly compared to younger
      patients (> or = 70 years: 40%; < 70 years: 40.8%), but 30-day mortality was
      higher in elderly (8.9% versus 2.8% in younger subjects). Elderly patients who
      died postoperatively presented a higher preoperative risk (ASA 2.75) compared to
      nonfatal cases in the same age group (ASA 2.18). Morbidity and mortality
      increased with the extent of surgery; the 30-day mortality was nil in the group
      of wedge and segmental resections (0/23), 1.9% in lobectomies (2/106) and 7.8% in
      pneumonectomies (4/51). Our results in general match those of comparable centers
      in Switzerland and the international literature. Since the overall complication
      rate was not increased compared to younger patients, we assume that polymorbidity
      of single cases was the cause of higher mortality after extended open lung
      surgery in septuagenarians and octogenarians. In consequence, the scope of
      surgery should be reduced as far as possible. In addition, the perioperative risk
      for the senescent patient can be improved by identification of high risk cases.
      With this attitude we take the view that lung resection can honestly be
      recommended to the elderly also.

PMID- 9148396
TI  - [Myocardial revascularization in geriatric patients].
AB  - The results of percutaneous transluminal coronary angioplasty (PTCA) in 71
      patients over 75 years of age were retrospectively analyzed and compared with
      those of 55 patients aged over 75 who underwent surgical revascularization (CABG)
      during the same time period (1992-1995). The main indication for
      revascularization was unstable angina. The clinical success in PTCA patients was
      92%, with a lesion success rate of 93%. Major cardiac complications occurred in
      5% of patients with an in-hospital mortality of 1%. The mean hospital stay was 4
      days. During a follow-up period of 16 (range 1-36) months, 23% of patients
      treated with PTCA needed repeat revascularization (17% PTCA, 6% CABG) and 4
      patients (6%) suffered nonfatal myocardial infarction. In-hospital mortality and
      complications were higher among the surgically treated patients (mortality 7%,
      major complications 45%), a fact probably related to their poorer clinical
      condition preoperatively. Repeat revascularization rate in the surgically treated
      group was 2%. The long-term mortality rate in both groups was 10%. Among long
      term survivors, 92% of patients indicated that revascularization (PTCA or CABG)
      improved their quality of life. More than 80% led normal lives, and > 90% would
      undergo a second procedure if needed. In selected patients aged over 75, PTCA has
      a high immediate success rate with low complications and mortality. Long-term
      recurrence rate is high, however, and repeat revascularizations are frequent.
      Patient satisfaction after myocardial revascularization (PTCA or CABG) is
      excellent and the majority of elderly patients can lead an active and independent
      life.

PMID- 9148398
TI  - [Inter- and intrahospital transmission of methicillin-resistant Staphylococcus
      aureus].
AB  - Occurrence and spread of methicillin-resistant Staphylococcus aureus (MRSA) has
      become a major problem worldwide. The majority of hospitals in Switzerland have
      not so far been affected by this epidemic. We report two out-breaks of MRSA
      transmission in the surgical intensive care unit at the University Hospital of
      Geneva and show the possible inter- and intrahospital dissemination of MRSA.
      Evidence for cross-infection is confirmed by epidemiological investigation and
      molecular typing. Infection control measures and general precautions are
      necessary to halt further spread of MRSA.

PMID- 9148399
TI  - [The prehospital phase of patients with suspected acute myocardial infarct:
      results of the Oltner Cardiac Emergency Study].
AB  - Early reperfusion in acute myocardial infarction has been shown to reduce
      myocardial damage and to improve prognosis. The goals of this study, the Olten
      Cardiac Emergency Study, were to identify the factors, related to the patients or
      to the emergency medical services, which influenced pre-hospital delay in
      patients with symptoms suggestive of acute myocardial infarction. From November
      1, 1992, to June 15, 1993, all the events occurring between symptom onset and
      hospital discharge where analyzed for 341 such patients who were cared for by the
      emergency networks connected with the Cantonal Hospital, Olten: in addition,
      follow-up at 3 months was obtained on all patients discharged alive. Of the 341
      patients, 14 (4.1%) died out of the hospital. The final diagnoses of the 327
      patients admitted to the emergency department were: acute myocardial infarction
      18.3%; unstable angina 10.1%; stable angina 3.4%; non-ischemic cardiac diseases
      29.4%; other non-cardiac diseases 38.8%. Mean delay between symptom onset and
      arrival at the hospital was 8 h 55 min (median delay 4 h 10 min); for patients
      with a final diagnosis of acute myocardial infarction, mean delay was 9 h 43 min
      (median delay 5 h 10 min). Patient delay was surprisingly long and represented
      70.4% of the total pre-hospital delay; 56.6% of the patients did not realize that
      their symptoms were serious and only 47.1% (and 68.3% of the patients with acute
      myocardial infarction) came to the hospital by ambulance. These long pre-hospital
      delays were responsible for the low (13.3%) thrombolysis rate of patients with
      acute myocardial infarction. We conclude that pre-hospital delay was much too
      long in our population. Improvements can only be achieved through patient
      education and better efficiency of emergency networks. Our findings underline the
      need for public education campaigns on heart attacks.

PMID- 9148400
TI  - [Prognosis in multiple sclerosis].
AB  - Prognosis of the natural course of multiple sclerosis is most often measured on
      Kurtzke's "expanded disability status scale" (EDSS), a non-linear scale over 20
      steps, heavily weighted on mobility. Optic neuritis and sensory disturbances as
      initial symptoms, lower age at onset of the disease, female sex and a longer
      interval between relapses are indicators of a more favorable prognosis. As a
      rule, disability as measured on this scale 5 years after onset corresponds to 3/4
      of the disability status after 15 years. The number of relapses diminishes
      naturally over the course of the disease. Presence and extent of lesions on the
      initial MRI of the brain in clinically isolated syndromes are valuable predictors
      of dissemination of the disease process over the following 5-10 years. New
      therapies (e.g. interferon beta 1b and 1a, copolymer 1) reduce relapse frequency
      by 1/3 and diminish the extent of pathological lesions in brain MRI, but fail to
      show (as yet) significant influence on disability.

PMID- 9148401
TI  - The start of something big? Dolly has become a new icon for science.

PMID- 9148402
TI  - Taming tremor. A pacemaker for the brain nears approval.

PMID- 9148403
TI  - Group brands AIDS trials unethical.

PMID- 9148404
TI  - AIDS trials ethics questioned.

PMID- 9148405
TI  - Publishing sensitive data: who calls the shots? Secrecy dispute pits Brown
      researcher against company.

PMID- 9148406
TI  - Publishing sensitive data: who calls the shots? Journals joust over conflict-of
      interest rules.

PMID- 9148407
TI  - Publishing sensitive data: who calls the shots? Secretiveness found widespread in
      life sciences.

PMID- 9148408
TI  - Publishing sensitive data: who calls the shots? Long-suppressed study finally
      sees light of day.

PMID- 9148409
TI  - Merck gives researchers knockout deal.

PMID- 9148410
TI  - The telomerase picture fills in.

PMID- 9148411
TI  - Possible function found for breast cancer genes.

PMID- 9148412
TI  - New vaccines may ward off urinary tract infections.

PMID- 9148413
TI  - Putative cancer gene shows up in development instead.

PMID- 9148414
TI  - Ideas on human origins evolve at anthropology gathering.

PMID- 9148415
TI  - Ribozymes in wonderland.

PMID- 9148416
TI  - Seeing the synapse.

PMID- 9148417
TI  - Current problems and the future of antiretroviral drug trials.

PMID- 9148418
TI  - [Blood donation: a constantly evolving concept].

PMID- 9148419
TI  - [Initial evaluation of the ACL-Futura coagulation analyzer].
AB  - PURPOSE: The first analytical performance of analyzer ACL-Futura (Instruments
      Laboratory) is presented. RESULTS: The analyzer shows an within-between day
      imprecision with controls, for PT (prothrombin time) of 0.7-8%, APTT (activated
      partial thromboplastin time) of 0.7-4%, fibrinogen (derived) 2-6%, ATIII
      (antithrombin III) of 3-9%, with specimens the imprecision is lowest. The
      linearity and carry-over for all the techniques were studied. An study of
      medicine interferences (Aspirin and Sintrom) and bilirubin, lipemia was
      performed. The reference values are presented. We study the practicability of the
      analyzer: technical difficulty, time consuming, determination cost and the
      usefulness in the urgency laboratory. CONCLUSION: These results validate the
      method to resolve the increased demand of these parameters.

PMID- 9148420
TI  - [Attitudes, beliefs, and motivations in blood donors and non-donors].
AB  - OBJECTIVE: To know and compare the beliefs, attitudes and motivations of donors
      and non-donors in relation with blood donation. MATERIAL AND METHODS: Transversal
      study by questionnaires administered to 197 blood donors and 303 non-donors. The
      questionnaires gathered: sociodemographic data, beliefs and attitudes (using a
      Likert scale), and motivations and demotivations (using upon questions). The
      responses were analysed using different descriptive analyses and bivariant tests,
      and factorial analysis and discriminant analysis were performed as multivariant
      analyses. RESULTS: The donor group had a mean age of 37.8 years, were 58.4 female
      and 41.6% male, and had made 6.02 donations. The non-donor group had a mean age
      of 39.8 years and were 53.8% female and 46.2 male. Regarding attitudes and
      beliefs, the donor group showed more confidence in the good conditions in which
      donations are performed, had less fears about the possibility that donation can
      affect health, their attitudes were generally less egotistical, and they had less
      fears about possible commercialisation of the blood. Both groups believed that
      blood banks and society itself give inadequate compensation to donors, but this
      belief was significantly greater among non-donors. Regarding the motivations of
      donors, the highest proportion were related with a sense of solidarity or duty
      (26.4%), followed by issues related with information or pressure (23.4%), and the
      possible personal or family benefits that donation might bring (21.8%). The
      initial motivations of most donors (75.9%) had not varied with the passage of
      time, and the factors found to be most demotivating for donation had to do with
      problems of access and comfort (74.6%). We would highlight that most non-donors
      denied any worries about blood donation (70.9%) and did not agree that those who
      need blood should be those who pay for it (92.8%). For non-donors, lack of
      information (43.6%) and different fears (32.3%) were the principal factors
      discouraging them from donating. Finally, discriminant analysis selected 11 of
      the items as providing 75.6% of correct discrimination between the one population
      and the other. CONCLUSIONS: Donors and non-donors reveal very different beliefs,
      attitudes and motivations towards blood donation, and the questionnaire employed
      in this study permits a high degree of discrimination between the two groups. The
      attitudes of non-donors towards donation are generally less favourable, but allow
      us to think that a high percentage of these could be changed with the right
      conditions.

PMID- 9148421
TI  - [Levels of cytokeratin CK19 expression in mononuclear blood cells evaluated using
      a reverse PCR (RT-PCR)].
AB  - AIMS: The sensitivity and specificity of a reverse transcription PCR method (RT
      PCR) to detect cytokeratin K19 (CK19) expression was evaluated with the purpose
      of assessing its capability to detect the presence of breast cancer tumour cells
      in peripheral blood progenitor cell collection that had to be reinfused to breast
      cancer patients submitted to intensive chemotherapy as haematopoietic support.
      PATIENTS AND METHODS: Two breast cancers as positive samples were used and 34
      samples of mononucleated blood cells as negative controls: 18 peripheral blood
      samples from normal subjects, 14 from different types of leukaemias (M3, M4Eo,
      M2, etc.) and two from two patients with Hodgkin's lymphoma. The method studied
      is a nested RT-PCR that amplifies the CK19 expression from the sample RNA
      extracted following the method of phenol-chloroform. RESULTS: The right
      performance of the method is demonstrated by observing the detection of CK19
      transcripts in the breast cancer RNA and by obtaining good blank results both
      with non transcribed RNA and with DNA. Moreover, the method has an excellent
      sensitivity such as to allow the detection of CK19 transcripts in a 10(-6)
      dilution of cDNA reverse transcribed from 1 microgram of breast cancer RNA. The
      CK19 transcripts were also detected in the 64% of RNA obtained from the
      mononucleated blood cells controls, although the percentage of positivities was
      lower (47%) in the RNA from peripheral blood samples. Nevertheless it should be
      remarked that the levels of CK19 expression in the blood mononucleated cells is
      almost negligible since it used to extinguish at 1:5 cDNA dilution. CONCLUSIONS:
      The method studied is specific and has a high sensitivity that explains the
      detection of CK19 illegitimate expression approximately a half in mononucleated
      blood cells negative controls. However, the levels of CK19 expression in
      mononucleated blood cells were almost negligible and it used to extinguish at 1:5
      cDNA dilution, therefore it could be concluded that the method might be useful to
      detect breast cancer occult tumours cells in mononucleated blood cell collection,
      always provided that a lower amount of cDNA is taken, thus decreasing to nil
      almost the false positive samples and keeping always a good sensitivity.

PMID- 9148422
TI  - [Polycythemia vera as a multiphasic clonal panmyelopathy: diagnostic profile,
      chronic pathological progression and effect of therapy on the survival of 74
      cases].
AB  - PURPOSE: 1. To recognise the clinico-biological profile of a group of patients
      diagnosed of polycythaemia vera (PV) in our centre in the last 30 years. 2. To
      identify the evolutive patterns of haematological transformation. 3. To evaluate
      the effect of therapy on the survival. PATIENTS AND METHODS: The clinical records
      of 74 patients (median age 62 years, male/female = 0.94, followed-up for 6-357
      months, median 64 months) were reviewed. Clinico-biological data at diagnosis,
      therapy, complications and evolution of the haematological picture were evaluated
      in each case. The actuarial survival in the series was compared to that of the
      normal population. RESULTS: The clinico-analytical data and diagnostic features
      were identical to other series reported. Mild increases of bone marrow reticulin
      was present in two thirds of the cases, overt myelofibrosis being found in only
      10% of the patients. Abnormal karyotype was seen in 9% of the patients (11q-, 
      Y). Phlebotomy was the only treatment in eight cases, without increased incidence
      of thrombotic phenomena. The remainders received myelosuppressive therapy (32P,
      busulphan, pipobroman, hydroxyurea, etc.), thrombotic complications appearing in
      8 cases and haemorrhagic complications in 4 others. One of these latter patients
      developed oesophageal carcinoma. The haematological picture evolved into toxic
      aplastic anaemia in 2 cases; myelofibrosis with myeloid metaplasia (MF/MM) in 8;
      myelodysplastic sindromes (MDS) in 5, three of them RAEB; and acute myelogenous
      leukaemia in 3 cases, two of them as the final stage of previous MF/MM and MDS/
      RAEB. The actuarial survival was 71% at ten years and 46% at fifteen years, and
      the median survival as a whole was 13.5 years. CONCLUSIONS: 1: The treatment,
      mostly myelosuppressive, given to these patients attained a survival similar to
      that of the general population. 2: Of the cases with known evolution, 15.6%
      developed MF/MM, its incidence being higher in patients treated only with
      phlebotomy (37%). 3: The incidence of malignant evolution, i.e., to RAEB/AML,
      amongst those patients followed-up was 10.6%.

PMID- 9148423
TI  - [Inhibitory factors in hematopoiesis: present and future].

PMID- 9148424
TI  - [Complete cytogenetic remission of chronic myeloid leukemia with low-dose
      interferon alfa-2b and monthly high-dose busulfan].
AB  - Two patients with chronic myelogenous leukaemia were treated according to an
      original regimen consisting of the association of alpha-2b interferon, three days
      a week, plus hydroxyurea during ten months, followed by interferon (same doses)
      and intermittent high doses of busulphan (50 mg, one dose per month, up to 6
      doses). Both patients achieved minor cytogenetic remission in the first stage
      (50% and 80% of Ph'-positive metaphases, respectively). Upon concluding the
      second phase, one patient attained complete cytogenetic remission and the other
      showed major cytogenetic remission (3% Ph'-positive metaphases); complete
      remission was achieved in the second patient after 4 more doses of busulphan.
      Both patients remain in complete cytogenetic remission after 4 and 2 years,
      respectively, with three weekly doses of interferon as maintenance therapy. This
      protocol is quite different to others applied so far and might represent a good
      choice for patients unsuitable for bone marrow transplantation.

PMID- 9148425
TI  - [Coexistence of chronic lymphoid leukemia and Hodgkin's disease.
      Immunohistochemical study].
AB  - We report a new case of coincidence of chronic lymphocytic leukemia (CLL) and
      mixed cellularity Hodgkin's disease (HD) in the same lymph node. These findings
      were corroborated by immunohistochemical study showing Reed-Sternberg (RS) cells,
      with typical immunophenotype in an inflammatory background, closely related to a
      small neoplastic lymphoid cell population. This is an uncommon feature, and, to
      our knowledge, this is the first case published in the Spanish literature.

PMID- 9148426
TI  - [Relation of spondylarthropathies and HLA-B27 antigen in patients from the state
      of Zulia, Venezuela].
AB  - HLA-B27 and associate antigens incidence were studied in 620 cases of
      seronegative spondiloarthropathies (SNS) and 262 controls of a Venezuelan mestizo
      population from Zulla state between 1985 and 1995. The incidence of HLA-B27 was
      20.96% of all cases of SNS. It was increased in patients with ankilosing
      spondylitis (AS) 33.33% and Relter's syndrome (RS) 30%, but not in uveitis (Uv)
      20% an psoriatic arthropathy (PsA) 0%. The incidence in the control group was
      4.2%. This results are lower than the previous description in Venezuelan mestizo
      and caucasic population but are close to the incidence described in population of
      West Africa with important contribution to admixture of the occidental part of
      Venezuela.

PMID- 9148427
TI  - [Morphological changes in the bone marrow of patients with HIV infection].

PMID- 9148428
TI  - [Apropos of the case "Erythroblastopenia associated with myelodysplastic
      syndrome"].

PMID- 9148429
TI  - [Bacterial contamination of platelet concentrates].

PMID- 9148430
TI  - [Seroprevalence of hepatitis A in Aragonese donors].

PMID- 9148431
TI  - [The eye of the beholder].

PMID- 9148432
TI  - [The therapeutic management of radiogenic oral mucositis].
AB  - BACKGROUND: Acute reactions of oral mucosa are a frequent side effect of
      radiotherapy, which often necessitates interruption of the treatment. Marked
      proliferation of tumor stem cells during treatment interruptions may occur in
      squamous cell carcinomata, which represent the majority of tumors in the head and
      neck area. Hence a fatal consequence of treatment breaks may be a significant
      decrease in tumor cure rates. Furthermore, marked acute responses frequently
      result in increased late sequelae ("consequential damage"). Therefore,
      amelioration of the mucosal response aiming at avoiding treatment breaks and at
      reduction of late reactions could definitely increase the therapeutic success of
      radiation treatment. PATIENTS AND METHOD: Various possibilities for the
      therapeutic management of radiation-induced oral mucositis with a symptomatic or
      radio- and epithelial biological background are summarized and presented
      systematically. RESULTS: A variety of prophylactic and therapeutic methods have
      been proposed for the management of acute radiation reactions of the oral mucosa.
      Frequently, their efficacy has been established for chemotherapy or in
      combination with other immunosuppressive treatments. Hence, systematical rather
      than local effects have to be considered. CONCLUSIONS: In general, prophylaxis of
      oral mucositis is mainly based on dental restoration or edentation, in
      combination with frequent oral hygienic measures after the meals and with
      antiseptic mouthwashes. Intensive personal care is recommended. The necessity of
      a percutaneous endoscopic gastrostoma is dependent on the status of the patient
      and on size and localization of the treatment area, i.e. the impairment of food
      uptake which is to be expected. Therapeutic intervention is restricted to local
      or systemic treatment of pain and local application of antimycotics and
      antibiotics.

PMID- 9148433
TI  - [Epicondylopathia humeri. The indication for, technic and clinical results of
      radiotherapy].
AB  - BACKGROUND: The efficacy of radiotherapy for degenerative-inflammatory disorders
      is well known, but so far long-term observations and reliable assessment of
      symptoms according to objective criteria and scores for validation are still
      missing. PATIENTS AND METHOD: From 1986 to 1991, 104 patients with refractory
      epicondylopathia humeri were irradiated. 85 patients or 93 elbows (due to double
      sided symptoms) were documented in long-term follow-up according to objective
      criteria. All patients had received intensive therapy. Pain symptoms were
      quantified in "categories" and "grades" prior to and 6 weeks after radiotherapy
      and at last follow-up. In addition, the elbow score of Morrey et al. [36] was
      used for long-term evaluation. The onset of pain symptoms was acute in 41 and
      chronic in 52 cases. The mean symptom duration prior to radiotherapy was 16
      months. Pain was mostly triggered off during professional (46) or sportive
      activities (23) or spontaneously (11). Fifty-one patients were severely disabled
      in professional or sportive activities. The involved elbow(s) received 2
      radiotherapy series of 6 x 1 Gy (total 12 Gy) with 3 fractions per week; the
      second radiotherapy series was started 6 weeks after the first series. Mean
      follow-up was 4 +/- 2 (1 to 8) years. RESULTS: Forty-three patients (50 elbows)
      achieved "complete pain relief (CR)" in all pain categories: 59% elbows with pain
      at strain had "complete pain relief", 79% with pain at night, 84% with permanent
      pain, 80% with pain at rest and 81% with pain at initiation or morning stiffness.
      Nineteen elbows gained "major pain relief (PR)", i.e. had minor symptoms (maximum
      grade 1) in all categories. Thus, a total of 69 (74%) elbows responded to
      radiotherapy. Seventeen patients (19 elbows) were operated because of persistent
      symptoms or dissatisfaction in long-term follow-up; 7 of those became completely
      free of symptoms. The Morrey-Score improved by a mean of 18 points from 78 prior
      to radiotherapy to 96 points at last follow-up. According to the Morrey-Score
      only 2 patients became worse in long-term follow-up. Two parameters indicated a
      negative prognosis in multivariate analysis: long symptom duration prior to
      radiotherapy and immobilisation with plaster (p < 0.05). CONCLUSIONS:
      Radiotherapy for refractory epicondylopathia humeri is highly effective. Long
      symptom duration and long-term immobilisation by plaster are negative prognostic
      factors for treatment outcome. Due to the low side effects and treatment costs,
      radiotherapy is a good therapeutic option in comparison to conventional treatment
      methods and surgery in the chronic stage of epicondylopathia humeri.

PMID- 9148434
TI  - [A phase-I/II study on the local hyperthermia of cervical N2/N3 lymph node
      metastases].
AB  - BACKGROUND: Patients with advanced lymph node metastases from head and neck
      tumors at stage N2/N3 (i.e. UICC IV) present a difficult therapeutic problem.
      Despite combined radio-chemotherapy and hyperfractionated and/or accelerated
      fractionation regimens, local control of these tumors remains unsatisfactory. For
      this reason, the value of local radio wave/microwave hyperthermia was examined
      for this patient group in a phase I/II study.

PMID- 9148436
TI  - [The clinical and pharmacokinetic results of intrapleural epirubicin
      application].

PMID- 9148435
TI  - [Spectrographic studies on the radioresistance of Miltex and miltefosine].
AB  - AIM: With simultaneous application of Miltex and radiation therapy in the
      combined treatment of topical relapses and skin metastases in breast carcinoma
      patients the question arises, how radioresistant is the new cytotoxic agent.
      Because of the long penetration times of the active agent miltefosine the answer
      is important with particular regard to the time of the external application of
      Miltex. MATERIAL AND METHOD: After the application of a single dose of 10 Gy we
      studied the stability of the commercial preparation and its active agent
      miltefosine by means of absorption spectroscopy. RESULTS: Immediately following
      the irradiation no alterations in absorption spectra of Miltex and miltefosine
      were found. However, 2 and 8 h post radiation the absorption curves of Miltex and
      miltefosine solutions were distinctly changed. The radiation induced changes of
      Miltex dilutions were smaller than those of the miltefosine solutions. For the
      commercial preparation the amount of the radiation-induced destruction is 0.10.
      CONCLUSIONS: Consequently Miltex has shown a sufficient radioresistance or its
      decrease in the effectiveness is small. With daily single doses of 2 Gy in the
      radiotherapy of the topical relapses and skin metastases the destruction degree
      should be reduced to 0.02 assuming linear changes. Because of the distinct
      changes in the spectra and relative slow penetration of miltefosine in various
      cell lines [10, 11, 14] we will propose an application of the commercial
      cytotoxic agent 5 h before the radiation fractions. The smaller effect on Miltex
      is discussed in relation to the solution mediators of the active agent.

PMID- 9148437
TI  - [Lymphatic vessel invasion in FIGO-stage-Ib cervical carcinoma: the prognostic
      relevance and role of adjuvant radiotherapy].

PMID- 9148438
TI  - [Improved survival through simultaneous radiochemotherapy versus radiotherapy
      alone in stage III of non-small-cell bronchial carcinoma].

PMID- 9148439
TI  - [The radio surgery of brain metastases].

PMID- 9148440
TI  - [Preoperative radiochemotherapy in bladder carcinomas].

PMID- 9148441
TI  - The influence of Edmund D. Pellegrino's Philosophy of Medicine.

PMID- 9148442
TI  - [Examination--myths and realities].

PMID- 9148443
TI  - [Atrial fibrillation--no benign heart arrhythmia].

PMID- 9148444
TI  - [Vaccination--a flagship of infection prevention].

PMID- 9148445
TI  - [Poliomyelitis--not an extinct disease. Outbreak of poliomyelitis in Vestlandet
      1950-54].
AB  - The last epidemic outbreak of poliomyelitis in Norway lasted from 1950 to 1954.
      The article describes the occurrence of poliomyelitis in Western Norway on the
      basis of 243 medical records from this period. The epidemic reached its peak in
      Western Norway in 1952, while the highest number of new cases of poliomyelitis in
      Norway as a whole occurred in 1951. We found equal representation of both sexes.
      Most cases were recorded in late summer and autumn. Most patients (96%) had
      general symptoms, most frequently headache. The fever was moderate. Meningeal
      irritation (neck stiffness) was recorded in 56% of the cases. The most frequent
      neurological symptom was asymmetric limb paralysis. 6% of the patients died. High
      fever, extensive paralysis and inadequate respiration had a negative effect on
      the prognosis. 57 patients had aparalytic poliomyelitis and were hospitalized for
      a short time.

PMID- 9148446
TI  - [Polio victims in Norway. Results of a national study 1994].
AB  - "The Norwegian Polio Study 1994" was conducted in order to survey the medical and
      social situation and the needs of polio victims. A questionnaire consisting of
      133 questions with subquestions was sent to a total of 2,392 polio victims in
      Norway. 1,449 persons responded, of whom 66% were between 45 and 64 years of age.
      When specifying new health problems, between 55% and 85% stated that they had
      experienced increasing weakness of the muscles affected by polio, weakness in
      previously non-affected muscles, fatigue, intolerance to cold and/or pain in
      muscles and joints. Only 17% were satisfied with the public health services for
      polio victims. On the other hand, 67% of those who had undergone a comprehensive
      evaluation and had been treated at a central hospital were satisfied. The study
      indicates an obvious need to build up expertise in multidisciplinary evaluation
      and treatment of post-polio victims.

PMID- 9148447
TI  - [Five year follow-up of patients with postpoliomyelitis syndrome].
AB  - The purpose of this investigation was to study subjective symptoms, medical and
      social situation, pulmonary function and physical work capacity over a period of
      3-5 years in patients with post-polio syndrome. We assessed a consecutive series
      of 68 patients admitted to our hospital because of post-polio syndrome, and re
      assessed 63 of these patients 3-5 years later; 43 women and 20 men with mean age
      55 +/- 10 (1 SD) years at the second evaluation. The patients answered a
      questionnaire about their subjective symptoms and medical and social situation,
      and underwent spirometry and symptom-limited exercise stress testing. Most
      patients experienced more serious symptoms and physical disability connected with
      their polio, while the majority reported that their psychological health was
      unchanged or had improved. Lung function was on average moderately reduced and of
      restrictive type, and only minor changes were found over the 3-5 years. A
      pronounced reduction in peak oxygen uptake was seen at the first evaluation,
      especially in women (59% of predicted). At the second examination, peak oxygen
      uptake was further reduced, especially in men, more than predicted by increasing
      age. The body weight and body mass index of the patients increased significantly
      during the same period. These results indicate that subjective symptoms and
      physical disability connected with polio increased with increasing age in these
      patients with post-polio syndrome, and cardio-respiratory deconditioning and
      weight gain also became more serious problems in most patients. The psychological
      status of the patients remained stable, however, or improved, possibly due to our
      comprehensive re-rehabilitation and educational programme.

PMID- 9148448
TI  - [The post-poliomyelitis syndrome--a real complication. A poliomyelitis material
      from the Haukeland hospital].
AB  - Over a four-year period, all in-patients at our department with the diagnosis of
      polio-sequelae were clinically examined for development of new neuromuscular
      deficit. 19 out of 125 patients (15%) had developed a postpolio syndrome. All 19
      had acquired additional functional deficit and 17 new, localized pareses. Five
      patients had developed polio-related hypoventilation. The mean time from acute
      poliomyelitis to debut of the post-polio syndrome was 39 years. The post-polio
      syndrome occurred in patients with severe pareses in the acute stage, but was not
      related to age, sex or specific epidemic. Most of the 106 other patients had
      similar subjective complaints but did not have any clinical signs indicating new
      neuromuscular deficit. 67 of these patients had tendinitis and/or myalgia and 83
      had chronic pain. Whereas many patients have progressive symptoms many years
      after poliomyelitis, only a minority develop the post-polio syndrome.

PMID- 9148449
TI  - [Phimosis can be treated with local steroids].
AB  - The effectiveness of topical steroid application in relieving phimosis was
      studied in 41 boys treated with a potent steroid ointment. 35 patients showed
      improvement initially but in 12 of them the phimosis recurred completely and in
      seven of them partly. There was significantly less recurrence in the patients who
      improved within one month. Most of the families were satisfied with the
      treatment. We recommend topical steroids as first treatment of choice for
      phimosis, when treatment is necessary.

PMID- 9148450
TI  - [Remittent seronegative symmetrical synovitis with pitting edema].
AB  - The symptoms and signs of remitting, seronegative symmetrical synovitis with
      pitting oedema (RS3PE-syndrome) are reviewed. Three patients with the disease are
      described, of whom one also developed multiple myeloma. All patients presented
      with diffuse swelling of the hands, consisting of both arthritis and oedema.
      Radiological examination did not disclose erosive changes, and all patients
      recovered. The article includes recommendations for clinical and laboratory
      investigations and therapy. The condition usually has a favourable outcome.

PMID- 9148451
TI  - [Cardiac manifestations in osteogenesis imperfecta. A case report and therapeutic
      implications].
AB  - Osteogenesis imperfecta is an hereditary defect in the synthesis of collagen
      fibres. The disease can cause cardiac defects, such as aortic and mitral
      incompetence. Surgical repair of these defects is complicated by tissue
      friability and bleeding problems. We describe a case where an incompetent aortic
      valve was successfully replaced by a mechanical prosthesis.

PMID- 9148452
TI  - [Shortage of physicians, leave of absence because of pregnancy and child care. A
      survey of physicians 1993].
AB  - The shortage of physicians is still a problem in Norway. In 1992, 344 (3.1%)
      physician full time equivalents (FTE) were "lost" because of family leave.
      Maternity leave averaged 34.7 weeks. 26% of the physicians who became a father in
      1992 took an average of three weeks paternity leave. Leaves related to other
      family responsibilities seem to be increasing among male physicians. Our
      estimates show that interruption of career, along with female physicians who
      choose to work shorter hours, will represent a discount of 452 (3.3%) physician
      FTEs in year 2002. If Norwegian physicians increase their leaves of absence in
      line with the possibilities provided by government regulations, this number will
      be even larger (4.5%). Changes in the pattern of career interruption should be
      considered when projecting the supply of physicians.

PMID- 9148453
TI  - [Treatment of heart failure with beta-blockaders].
AB  - Since 1975 several studies have indicated that treatment with beta-adrenergic
      blocking drugs has a positive effect on prognosis in patients with left
      ventricular dysfunction. After myocardial infarction, treatment with timolol and
      propranolol improves prognosis in patients with symptoms of cardiomegaly and
      heart failure. In patients with idiopathic dilated cardiomyopathy, treatment with
      metoprolol improves the left ventricular ejection fraction and symptoms of heart
      failure, and may have a positive effect on prognosis. Recent studies of patients
      with chronic congestive heart failure also indicate that carvedilol has a
      positive effect on mortality and morbidity. The authors review some relevant
      studies, to stimulate the use of beta-adrenergic blocking drugs to treat certain
      types of heart failure.

PMID- 9148454
TI  - [Unacceptable quality in certain sectors of medical research].
AB  - Errors have become so common in certain sectors of medical research that the
      situation has been described as a scandal. The criticism applies in particular to
      research based on measurements, where incorrect application of mathematical and
      statistical methods has become accepted as the correct approach. This has had
      unacceptable practical consequences, and the situation requires immediate steps
      to raise the level of quality. The author discusses some basic aspects of
      measurements in general, and serious errors associated with bone mineral
      measurements in particular.

PMID- 9148455
TI  - [Is the governmental vocational rehabilitation program too ambitious?].
AB  - The Norwegian government has stressed the importance of supporting vocational
      training for clients with health problems in order to secure their active
      participation in the labour force. On average, 35,000-40,000 people were referred
      from the National Insurance Scheme to the Directorate of Labour to take part in
      vocational rehabilitation projects in 1995. The majority of the vocationally
      handicapped are young. Three out of four have a poor educational background, and
      close to 70% have health problems, mainly in the form of chronic musculoskeletal
      pain or psychiatric illness, usually depression and anxiety-states. So far, the
      success of the rehabilitation seems to be rather limited, since approximately 40%
      of the clients were referred back to the Insurance Scheme. They were considered
      unfit for training because of impaired health. Another 40% of the cases were
      considered fully or partly successful. Clients with psychiatric illness seem to
      be particularly difficult to rehabilitate to vocational activity.

PMID- 9148456
TI  - [Working with scientific consultants. Background and needs for practice
      guidelines].

PMID- 9148457
TI  - [Some experiences with hospital-based psychiatric aftercare over ten years].

PMID- 9148458
TI  - [Thoughts on forensic psychiatry after visits to two neighbouring countries].

PMID- 9148459
TI  - [Mortality among substance abusers after admission to different institutions].

PMID- 9148460
TI  - [Pregnancy interruption in group 1 hospitals in 1996].

PMID- 9148461
TI  - [The Marvelon issue and confidence towards oral contraceptives].

PMID- 9148462
TI  - [Adopted children and big stomachs].

PMID- 9148463
TI  - [A rapid Helicobacter test in general practice. A needed test or a textbook
      example of how to create health issues?].

PMID- 9148464
TI  - [Common sense won, but the fight is not over!].

PMID- 9148465
TI  - [Low molecular weight heparin in acute ischemic cerebrovascular disease].

PMID- 9148466
TI  - [Polycythemia's victory].

PMID- 9148467
TI  - [The good death?].

PMID- 9148468
TI  - [Human reactions to extreme stress].

PMID- 9148469
TI  - [Animal experimentation--is it defensible?].

PMID- 9148470
TI  - [Identification of bodies in mass disasters. The aircraft on Svalbard].

PMID- 9148471
TI  - [Transplantation of animal organs (xenotransplantation). Status and future
      development].
AB  - The increasing shortage of human organs for allotransplantation has created
      intense interest for xenotransplantation. Pig organs have been suggested as
      suitable grafts for man. However, the immediate problem associated with
      discordant xenotransplantation is hyperacute rejection. Hyperacute rejection
      occurs because antibodies become attached to the endothelial cells of the
      xenotransplant organ, which activates the complement system, attracts platelets
      etc. This results in endothelial cell damage, oedema, loss of vascular integrity
      and thus rapid destruction of the graft. Organs from non-human primates often do
      not cause hyperacute rejection, but will probably not be acceptable donors.
      Transgenic pigs have been breeded which contain the genes for the human
      regulators of complement activation. It appears that insertion of such genes into
      pigs serves to prevent aggressive hyperacute rejection. Understanding the
      mechanisms of rejection gives cause for optimism. However, there are still many
      problems to evaluate and solve. One potential danger associated with
      xenotransplantation is the transmission of infectious disease from animals to
      man. Other problems relate to physiological adaptation of the xenograft. The
      legal, ethical, religious and economic aspects must also be taken into
      consideration. Despite the potential problems, it is likely that a xenotransplant
      of some kind will soon be attempted in man.

PMID- 9148472
TI  - [Check up of breast cancer stages 1 and 2].
AB  - We have studied the efficacy of investigations during follow-up of 430 operable
      node positive and node negative breast cancer patients. Median follow-up was
      eight years, and 128 patients had relapsed, 91 with metastatic disease. Eight
      blood analyses, chest X-ray, limited skeletal X-ray and bone scan examinations
      were undertaken at regular intervals. Of the patients who had relapsed, 59% had
      symptoms, 23% were detected by clinical examination and 18% were detected by
      blood analysis only. X-rays and scintigrams were of little value in proportion to
      the costs. The combination of three blood analyses was useful. An increase in
      sedimentation rate (ESR) of more than 10 mm/h, an increase in gamma
      glutamyltransferase (GT) of 20 U/l and an increase in alkaline phosphatase (ALP)
      of 60 U/l or more. By using ESR, gamma-GT, ALP, history and clinical examination,
      costs could be reduced by 90% while maintaining adequate baseline screening for
      relapse.

PMID- 9148473
TI  - [Bladder tumor, metastasis from breast carcinoma. A case report with literature
      review].
AB  - Breast cancer is the most common type of cancer amongst. Norwegian women. It
      spreads to various localisations, the most usual foci being lymphatic nodes,
      lungs, liver and bone. For a long time, metastatic breast cancer to the urinary
      bladder has been considered an extremely rare manifestation. We describe one case
      in which metastasis to the bladder from breast cancer caused clinically important
      symptoms. We discuss the pathophysiology, symptoms and diagnostic tools in regard
      to this rare phenomenon, and why bladder metastasis from breast cancer has
      become, and will continue to become increasingly important.

PMID- 9148474
TI  - [Health status survey in a district with many immigrant children].
AB  - In Norway, prophylactic child health care is organized through local mother and
      child clinics, each of which serves a given population. This study summarizes the
      findings from the routine check-up of four-year-olds in a district with a high
      proportion of immigrant families. The sample consisted of 70 children, 33 of them
      from immigrant families. The ordinary check-up was supplemented by information
      obtained by means of a questionnaire, which was filled in by the public health
      nurse and the doctor in consultation with the parents. A validated scale, or
      checklist (BCL), for ordinary behavioural problems among pre-school children was
      also included. The findings must be interpreted with caution, one reason being
      the large socio-economic differences between the immigrant and the Norwegian
      families included in the study. Nevertheless, the difference between the eating
      habits of the two groups of children was striking, in spite of the emphasis
      placed on diet at the clinic. Another important finding was the poor knowledge of
      Norwegian among the immigrant children, which was obviously associated with the
      poor language skills of the mothers. Therefore, an important element of the
      preventive health work among immigrant children should be to encourage the
      mothers to attend courses in Norwegian.

PMID- 9148475
TI  - [Strain tendinitis--short-term treatment with antiphlogistics. Experiences from a
      four-day march in Nijmegen 1996].
AB  - In the course of the four-day march in Nijmegen, 150 participating soldiers
      consulted a doctor. 128 of these soldiers suffered from tendinitis in the lower
      extremities. These patients were treated with naproxen 250 mg three times a day
      for the rest of the march. Of the 106 patients who answered a questionnaire
      evaluating the treatment, 10.5% had not felt any improvement at all, whereas
      89.5% reported improvement or a complete cure from the treatment. Four weeks
      after the march, 36 persons still reported persistent pain during physical
      activity. The results indicate that short-term treatment can be beneficial for
      some but have disadvantages for others.

PMID- 9148476
TI  - [Positive feedback for good medical work--a short-supply commodity?].
AB  - In a nationwide survey of the working environment of Norwegian physicians every
      second respondent reported seldom or never being appreciated or praised for good
      work by their superiors. Nurses, colleagues and auxiliaries are more frequent
      sources of such appreciation. Very little of the variance in doctors' experience
      of positive feedback is explained by job variables: a doctor who does not receive
      supportive feedback cannot attribute this to unwise choice of specialty or type
      of employer, or to age, sex or position in the hierarchy. The experiences of male
      and female doctors are very much the same. Whether the doctors are appreciated
      and praised for good work seems to depend rather on certain traits of their
      personality.

PMID- 9148477
TI  - [Daily number of births in Norway 1989-93. Variations across months, day of week,
      phase of the moon and changes in leave entitlements].
AB  - The variation in the daily numbers of births across month, day of week, phase of
      the moon and maternity leave entitlements have been studied for all births in
      Norway between 1989 and 1993, a total of 302,209 newborn children. The number of
      births was highest in the spring and lowest in November and December. A secondary
      birth maximum was observed in September, possibly related to activities during
      Christmas and New Year celebrations nine months before. Furthermore, births were
      least numerous at weekends and were concentrated in the middle of the week. This
      pattern probably reflects less active obstetric intervention at weekends. The
      number of births does not seem to vary with phase of the moon. At the time of the
      latest, and largest increase in national birth maternity leave entitlements,
      fewer births occurred in the days before and correspondingly more births in the
      days immediately after the date when the change came into force.

PMID- 9148478
TI  - [Skiing over Greenland--physical and psychological changes].
AB  - Three Norwegian physicians crossed the inland glacier of Greenland on skis
      without any support. Body weight, fat and lean body mass was measured by dual X
      ray absorptiometry scanning. Maximal oxygen uptake, lung capacity measurements,
      and various blood tests were recorded. Subjective health-related well-being and
      four transistory arousal states were also recorded (GHQ-30 and AD ACL, short
      form). One participant lost 1 kilo body weight, while the others gained 1 and 4
      kilos, respectively, during the trip. Overall, lean body mass increased (1.2-4.0
      kg), while body fat was reduced (0.4-2.7 kg). These changes reversed after four
      weeks. Bone mass, lung function and blood tests did not vary throughout the study
      period. The level of energy and calmness were high at baseline and even higher
      towards the end of the expedition, while the scores were low and stable for
      tiredness and tension. Subjective well-being increased for all participants
      towards the second half of the trip. We conclude that expeditions involving
      physical and mental strain can produce positive psychological changes. Catabolic
      conditions are avoidable. Changes in body mass composition revert quickly.

PMID- 9148479
TI  - [Acute high altitude sickness--medical experiences from Mount Everest during the
      spring season 1996].
AB  - In April-May 1996 a Norwegian expedition climbed Mount Everest from the Tibetan
      side, Eight out of the ten members reached the summit. The expedition did not
      experience any serious incidents but took part in the rescue and treatment of
      climbers from other expeditions. Eleven cases are reported. Four of these were
      fatal. Cerebral oedema and frostbite were the most common problems in addition to
      hypothermia and exhaustion. The author also discusses acute mountain sickness,
      including clinical features, treatment and prophylaxis.

PMID- 9148480
TI  - [Dr Alexander M. Kellas and the first Mount Everest expedition].
AB  - In 1921 the government of Tibet gave permission for a British party to attempt
      Mount Everest from the northern Tibetan side. Little was known about the
      physiological and medical problems associated with ascents to extreme altitudes.
      The person who knew most about these topics was Dr. Alexander Kellas, lecturer in
      medical chemistry at the Middlesex Hospital Medical School. He had made a number
      of expeditions to the Sikkim Himal and the Tibetan border before the first world
      war, and had become increasingly interested in the problems caused by altitude.
      He was invited to join the Everest expedition but died on the approach march at
      Kampa Dzong on the Tibetan plateau, within sight of the mountain. Before he went
      on the expedition Kellas wrote an article entitled A consideration of the
      possibility of ascending Mt. Everest. This paper was never published, but the
      manuscript exists in the archives of the Royal Geographical Society and the
      Alpine Club in London. As Kellas saw it, the main issue was whether sufficient
      adaptation could occur to allow a climber to ascend from a camp at about 7,700 m
      to the summit (8,848 m) in one day without supplementary oxygen. His conclusion
      was that this was possible and, in fact, the first such ascent by Habeler and
      Messner in 1978 started from a camp at 7,900 m. Kellas calculated the pressure on
      the summit to be 251 mmHg, a more accurate figure than estimates based on the
      "Standard Atmosphere" Kellas estimated maximum oxygen uptake at the summit to be
      970 ml/min, and the current value is thought to be about 1,070 ml/min. His
      estimates of the climbing rate near the summit closely parallels the rate of
      Habeler and Messner. Kellas had a talent for asking the right questions. He
      applied his considerable knowledge of physiology to the topic of high altitude,
      and his suggestions and recommendations were of consistently high quality. He
      deserves to be better known, both for his geographical surveys and for his
      pioneer work on high altitude medicine and acclimatisation. The 1921 expedition,
      after many failed attempts, discovered a possible route to the top of Mount
      Everest, which was used on all the summit attempts between the two world wars.
      The route went from Kharta, over the pass Lhakpa La, across East Rongbuk glacier
      and up via the north col.

PMID- 9148481
TI  - [Medical holocaust. "Euthanasia" in Germany cca. 1935-45].
AB  - The method used in the industrialised mass murder of Jews was developed and
      tested within German psychiatry, where as many as 200,000 people were murdered
      under the "Euthanasia Programme". The doctors' professional enthusiasm for this
      programme, their distant contemplation of "life unworthy of life", can be
      understood as the establishment and legitimisation of certain rules of speech,
      which caused them to "forget" that they were dealing with people. Thus, German
      medicine was an important supplier of premises for the Nazi's extermination
      policy.

PMID- 9148482
TI  - [Ending life by medical means. Do attitudes of physicians differ from those of
      the population?].
AB  - The paper presents the Norwegian population's attitude to euthanasia and to legal
      abortion in 1982, 1990 and 1995, and compares the responses given in 1995 with
      the attitudes of a representative sample of 1,260 Norwegian physicians. The
      acceptance of legal abortion in the population seems to have remained constant,
      while the population's attitude towards euthanasia has become more liberal.
      Social criteria and a potential handicapped baby were less accepted as causes for
      abortion in 1995 than in 1990. The physicians are more liberal towards abortion
      and more sceptical towards euthanasia. The physicians are more reluctant,
      however, to accept a potential handicapped offspring as a reason for abortion.

PMID- 9148483
TI  - [A course in medical ethics--a pain in the neck for the clinicians?].
AB  - Last year, a course in clinical medical ethics for paediatricians had to be
      cancelled owing to lack of interest. To find the reason for this, and to learn
      what ethical problems the physicians encountered in the course of their work, how
      they solved them, and their attitude towards education in medical ethics, a
      questionnaire was sent to all members of The Norwegian Paediatric Association, to
      be answered anonymously. The most frequent excuses for not attending the course
      were pressure of work and lack of time. 37% claimed that they very often or often
      encountered ethical problems during their work. 20% often solved these problems
      alone, and two out of three after discussing them with colleagues. 51% felt a
      need to improve their competence to solve ethical problems. Only 16% reported
      having no such need. The authors discuss the form and content of the education in
      medical ethics.

PMID- 9148484
TI  - [Nature medicine as intoxicant].
AB  - Documentation is often scarce about adverse effects of herbal products used in
      alternative medicine. Five patients were admitted to hospital with altered
      consciousness after taking the herbal product Relaxir, a remedy for insomnia and
      restlessness, produced mainly from the fruit from the passion flower (Passiflora
      incarnata). Relaxir is thought to have an intoxicating and sedative effect and
      may also potentiate the effect of other drugs. It is questionable that herbal
      products liable to cause intoxication are sold without restriction.

PMID- 9148485
TI  - [Euthanasia as a topic in criminal literature. Two examples].
AB  - Euthanasia is the main theme in the crime novels. The sisterhood by the American
      author Michael Palmer, published in 1982 and Morfindoktoren nekter seg skyldig
      (The morphine doctor denies his guilt) by the Norwegian author Waldemar Brogger,
      published in 1958. In spite of differences between these two novels in time and
      space, they show many similarities. In this article the two novels, both of which
      have physicians as the main characters, are compared. Biographic information on
      the authors confirms the hypothesis of a close relationship between authors and
      their heroes in the criminal literature. The criminal literature has many points
      of connection in the medicine. These two examples show how even important and
      difficult medical ethical issues can be a subject for a crime novel.

PMID- 9148486
TI  - [With the microscope as weapon. A comment to criminal novels by Patricia D.
      Cornwell].
AB  - Patricia D. Cornwell has had a remarkable success with her books about Dr. Kay
      Scarpetta, a forensic pathologist and lawyer in Richmond, Virginia, on the east
      coast of USA. Cornwell's authorship is characterised by a combination of forensic
      details and thrilling stories about serial killers and other maniacs. Her books
      have reached the top of the bestseller lists for years.

PMID- 9148487
TI  - [Neurology--a specialty with own criminal novels. Neurological topics in
      Norwegian criminal literature].
AB  - The authors of a large number of Norwegian detective stories, particularly from
      the first part of this century, are occupied with neurologists and
      neurobiological problems. A survey of this literature shows. One Norwegian
      neurologist has written four detective stories. Not one single neurologist can be
      found as a detective hero. On the other hand there are numerous examples of the
      neurologist as a criminal or even a murderer. Neurological symptoms and signs
      (mostly functional pareses and epileptic fits) are used to construct the plot in
      other novels. The most striking finding is a detective story where the criminal
      is a neurobiologist, the plot is based on neurobiology and the author discusses
      neurological phenomena throughout the entire book.

PMID- 9148488
TI  - [Medical topics in thrillers].

PMID- 9148489
TI  - [Confusion dialogues. A critical look at the clinical development].

PMID- 9148490
TI  - [Happy pills with a funny taste. Some reflections on a clinical paradox].

PMID- 9148491
TI  - [Risk prevention. Correct information may be misleading].

PMID- 9148492
TI  - [The system of assigned physicians].

PMID- 9148493
TI  - [Where euthanasia is an everyday event].

PMID- 9148494
TI  - [Norwegian policy on alcohol use and the Norwegian Medical Society].

PMID- 9148495
TI  - [When should we start to drink?].

PMID- 9148496
TI  - [Screening of pregnant women for toxoplasma infection].

PMID- 9148497
TI  - [Whiplash injuries].

PMID- 9148499
TI  - [Nasal polyps and adenoid vegetations].

PMID- 9148498
TI  - [Androgenic blockade in metastasizing prostatic carcinoma].

PMID- 9148501
TI  - [Atrial fibrillation--no malignant heart arrhythmia].

PMID- 9148500
TI  - [Zocor and Sotacor].

PMID- 9148502
TI  - [Medical expert consultation. Is there an alternative?].

PMID- 9148503
TI  - [Simultaneous occurrence of different diseases].

PMID- 9148504
TI  - [Training of sport-divers and directions on its methods].

PMID- 9148505
TI  - [Brain concussion--a case report].

PMID- 9148506
TI  - [An estimation of the level of epithelial cell differentiation in impressions
      from different sites of the oral mucosa in healthy persons].
AB  - Impressions from various sites of the buccal mucosa of 20 normal subjects aged 16
      to 33 years were examined. Mature epitheliocytes of the V differentiation stage
      predominate in the cytological impressions of the lingual and buccal mucosa.
      Cells of the V stage of differentiation predominate in the lower lip mucosa, and
      there are just few cells of the IV (transitional) stage. In impressions of the
      palatal mucosa mainly cells without nuclei (stage IV) were found. These data will
      help more objectively assess the cytological findings in different diseases
      involving the buccal mucosa.

PMID- 9148507
TI  - [Lymphotropic therapy with trental in the treatment of chronic herpetic
      stomatitis].
AB  - Lymphotropic therapy with trental was administered to patients with chronic
      herpetic stomatitis. Trental was injected near the mastoid process after
      preinjection with lidase (total dose no more than 1 ml on each side, 6 sessions
      per course). The treatment normalized the immune status, clinical symptoms
      regressed sooner than after treatment with an antiviral agent bonafton,
      remissions were prolonged, and in 5 out of 18 patients no more relapses occurred.

PMID- 9148508
TI  - [Involvement of the temporomandibular joints in Bechterew's disease].
AB  - Temporomandibular joints are involved in Bechterew's diseases in 59.6% of cases,
      more often in the peripheral form of the disease. Involvement at the debut of the
      disease was observed in 33.3%, including monoarthritis in 28.6%. The incidence of
      these lesions correlated with involvement of the hip, knee, and ankle joints.
      Unstable symmetrical arthritides with early rigidity predominate in the clinical
      picture. Extraarticular symptoms, such as defiguration, tenosynovitis, are
      typical. X-ray examination reveals pseudodilatation of the joint fissure,
      periarticular osteosclerosis, ossification of the ligaments, early ankylosis
      without predestruction. Erosive changes of the temporomandibular joint are not
      typical. Scintigraphy with pertechnephore is an informative method for ruling out
      other diseases of the temporomandibular joint.

PMID- 9148509
TI  - [The current potentials of maxillofacial surgery].
AB  - Autotransplants of membranous origin and titanium constructions were used in 462
      patients with posttraumatic defects and deformations of the upper and medium
      zones of the facial skeleton. Stable functional and cosmetic results were
      attained in repair of diplopia and enophthalmos. Surgical methods proposed by the
      authors accelerate patients' rehabilitation.

PMID- 9148510
TI  - [Mandibular resection and reconstruction by an intraoral approach].
AB  - Resection and reconstruction of the mandible by intraoral way. The results of
      resection and reconstruction of the mandible for 12 patients with benign tumors
      and dysplastic processes by intraoral way are introduced. Indications and the
      surgery are developed and long-term outcomes are considered. Patients observation
      for several years proved these suggested methods to be effective.

PMID- 9148511
TI  - [The differential diagnosis of lymphogranulomatosis (Hodgkin's disease) and
      sialoadenitis of the submandibular salivary gland].
AB  - A case of Hodgkin's disease with local involvement of the submandibular area is
      described. Profound examinations found that the tumor did not originate from the
      salivary gland. Anatomic examination of the resected tumor revealed Hodgkin's
      diseases. The authors emphasize the necessity of differential diagnosis between
      Hodgkin's disease and chronic sialadenitis.

PMID- 9148512
TI  - [Immunocorrection in the combined treatment of patients with sialoadenitis].

PMID- 9148513
TI  - [Computed tomographic and clinical validation of the use of endosseous titanium
      nickelide dental implants].
AB  - The authors analyze the efficacy of repair of atrophied [correction of
      arthrophic] alveolar processes of the jaws in the projections of the maxillary
      sinus and inferior alveolar canal with endosseous implants with porous cone
      dilating mesostructure made of TN-1P alloy. Prospects for using the new implant
      design are outlined.

PMID- 9148514
TI  - [A modified method for the volumetric modelling of the base for a complete
      removable denture].
AB  - A modified method of bulky modeling of the basis of a complete removable denture
      is proposed. The author considers that it will permit forming all the surfaces of
      the basis for complete removable denture under mastication pressure and with the
      mouth closed under conditions maximally approximated to those when the denture
      will be used.

PMID- 9148515
TI  - [The finishing treatment of dentures made from corrosion-resistant steel].
AB  - Validates the new technology of processing dentures made of corrosion-resistant
      steel. The method is based on using modern abrasives (synthetic diamonds and
      spheric corundums), polymers, and organosilicon compounds for grinding and
      polishing instruments.

PMID- 9148516
TI  - [The characteristics of local anesthesia in children].

PMID- 9148517
TI  - [The principles of orthodontic treatment by the Alexander discipline].

PMID- 9148518
TI  - [A new orthodontic apparatus for the vertical traction of the teeth of adults].
AB  - A device for the treatment of vertical abnormalities of occlusion in adults is
      proposed. It permits a simultaneous vertically directed moving of a group of
      teeth.

PMID- 9148519
TI  - [Optodan: a new-generation laser semiconductor physiotherapeutic device].
AB  - The design of a new-generation semiconductor laser with automated operate is
      described (wavelength 0.85 to 0.95 mm, power up to 4 W, frequency 0.1 to 3 kHz)
      and potentialities of its use for laser physio- and reflex therapy of
      stomatological and general somatic diseases after the authors (patented and
      certified) methods outlined, including computer-aided laser systems for the
      differential diagnosis and treatment.

PMID- 9148520
TI  - [The seasonal patterns of surgical morbidity of the maxillofacial area under the
      climatic conditions of the city of Derbent].
AB  - Analysis of 724 case histories over many years permitted the author to
      distinguish the seasonal regularities in the development of various
      stomatological diseases, differing by the etiology and pathogenesis: furuncles on
      the face, mandibular fractures, and lymphadenitis of the maxillofacial area and
      neck. Under the climatic conditions of the town of Derbent a seasonal rise in the
      incidence of furuncles of the face is observed in July, August, and September,
      that of mandibular fractures in May, and July, and of lymphadenitis in January,
      February, July, and August.

PMID- 9148521
TI  - [Diprivan (propofol) in the anesthesiological support of outpatient dental
      interventions].

PMID- 9148522
TI  - [Means for enhancing the quality of therapeutic work].

PMID- 9148523
TI  - [The accreditation and certification of specialists in dentistry].

PMID- 9148524
TI  - [Additional attachments and possibilities of the V. F. Rud'ko device].

PMID- 9148525
TI  - [The suction attachment of a foreign body to the mucosa of the hard palate (a
      clinical case)].

PMID- 9148526
TI  - [Paradoxes of dentistry (information for reflection)].

PMID- 9148527
TI  - [Danish scientific research--in international journals and in the Ugeskrift].

PMID- 9148528
TI  - [Circulatory diseases in the legs].

PMID- 9148529
TI  - [Mechanisms of pain and genetics in migraine].

PMID- 9148530
TI  - [The need for humanistic research in medicine].
AB  - The need for humanities in medicine is often discussed these years. Results from
      qualitative studies are now published in many medical journals. This article
      describes some characteristics of qualitative research and presents its
      theoretical basis. To give a better understanding of the qualitative research
      process, it is here compared with the clinical process. This analogy is
      reasonable because the qualitative researcher just as the clinician performs data
      collection and data analysis during the same process. The most important aspect
      of qualitative research is not "to measure" but "to understand" something. And
      understanding is created through concepts that makes phenomena and events
      "conceivable". The conceptual work in qualitative research is of great
      importance. The relation between traditional medical research and medical
      humanities is such that we need both, because the one cannot solve the others'
      tasks, and vice versa. It is worth while remembering that an engagement in the
      one research area does not exclude respect for the other research areas'
      potential and value.

PMID- 9148531
TI  - [Extraintestinal Salmonella infections in four Danish counties. Inverse
      relationship between invasiveness and zoonotic serotypes].
AB  - The relationship between invasiveness and incidence of non-typhoid salmonellosis
      was ascertained retrospectively in a population of 1.9 million in four Danish
      counties during the three-year period 1992-1994. The study comprised 4175 cases
      diagnosed by culture either locally or at Statens Serum Institut, Copenhagen. Two
      hundred and forty-four patients had extraintestinal infections caused by 24 out
      of the total number of 101 different serotypes. Invasiveness ranged widely from
      4% to > 90% for individual serotypes. Salmonella typhimurium and Salmonella
      enteritidis formed a high-incidence group (incidence rates > or =
      25/100,000/year) compared to the remaining 22 serotypes (< 5/100,000/year). The
      low-incidence group was more invasive than the high-incidence group even when
      excluding Salmonella dublin, which is highly invasive, and including 212 cases of
      salmonelloses caused by serotypes isolated entirely from faeces (relative risk
      1.54, 95% confidence limits 1.19 < RR < 2.00). The data corroborate a previous
      more limited study and indicate that previous exposure to salmonella and acquired
      immunity may play a role in the occurrence of extraintestinal non-typhoid
      salmonellosis.

PMID- 9148532
TI  - [Treatment of cancer pain in Denmark. A questionnaire survey].
AB  - A questionnaire survey was carried out with the aim of evaluating knowledge about
      and practice of cancer pain treatment in Denmark. A questionnaire was sent to a
      10% random sample of Danish physicians. Of these 1411 physicians, 1068 (76%)
      returned the questionnaires and after the exclusion of those doctors who never
      treated cancer patients, 577 (54%) were analyzed. Their knowledge of the
      principles and practice of cancer pain treatment was evaluated by means of 14
      multiple-choice and open questions. Their ability to apply their knowledge in
      practice was evaluated by analyzing their suggested treatment of three simulated
      patient cases. Ninety-seven percent of the physicians recognized difficulties in
      cancer pain treatment, the most frequent being side effects of drugs and
      inadequate pain relief. It appeared from the proposals for pain treatment of the
      patient cases that the majority of the physicians could treat both pain from bone
      metastasis (75%) and visceral pain (78%) satisfactorily, while very few suggested
      coanalgesics for neuropathic pain (20%). Older physicians performed less
      satisfactorily than did their younger colleagues. Basic pain treatment skills
      have been acquired by the Danish physicians. However, in the future emphasis
      should be placed on the treatment of neuropathic pain with coanalgesics and the
      management of opioid side-effects.

PMID- 9148533
TI  - [Lumbar disk prolapse surgery with or without free fat transplantation. A
      prospective triple-blind randomized study].
AB  - The aim of this prospective triple-blind randomized study was to determine if a
      free fat transplant used in operation in lumbar disc herniation could reduce the
      degree of intraspinal scar tissue and to evaluate whether the scar tissue could
      lead to symptoms. Ninety-nine patients were subsequently examined after median
      376 days. The clinical outcome was scored using the Low Back Pain Rating Scale.
      Enhanced CT-scanning was assessed regarding the degree of scar tissue and
      survival of the fat transplant. There was no difference in the clinical outcome
      between the two groups. Significantly fewer had dural scarring in the group who
      had a free fat transplantation, but there was no difference regarding the degree
      of radicular scarring. The transplant was shown on CT-scan at the follow-up
      examination in 66% of the patients who had a fat transplantation. Free fat
      transplantation can reduce the degree of dural scar tissue after operation for
      lumbal disc herniation, but does not result in a clinically better outcome.

PMID- 9148534
TI  - [Mask physiotherapy for prevention of pulmonary complications after heart
      surgery. A controlled study].
AB  - The objective of this prospective, consecutive, randomized, controlled study was
      to investigate the effects of mask physiotherapy on postoperative complications
      after heart surgery. Sixty-six low-risk male patients undergoing coronary artery
      by-pass graft surgery were evaluated. The patients were treated with routine
      chest physiotherapy alone or supplied with either positive expiratory pressure
      (PEP), or inspiratory resistance-positive expiratory pressure (IR-PEP).
      Postoperative pulmonary complications were assessed by forced vital capacity
      (FVC), arterial oxygen tension (PaO2), and chest X-ray examination. There was an
      almost equal decrease and subsequent rise in spirometric and blood gas values in
      all three groups, but patients treated with the PEP mask had a borderline
      significantly higher increase in PaO2 from day three to day six compared with
      patients treated with no mask. There was an almost equal frequency of atelectasis
      in the three treatment groups. It is concluded that no significant differences in
      outcome were found between the three groups.

PMID- 9148535
TI  - [Activated protein C resistance in patients with venous leg ulcer].
AB  - Patients with venous leg ulcers often show evidence of previous deep venous
      thrombosis. Resistance to activated protein C (APC-resistance) is an autosomal
      dominant inherited defect in the anticoagulant system which is a significant risk
      factor for development of venous thrombosis. APC-resistance was determined in
      plasma samples obtained from 46 unselected, consecutively admitted patients with
      venous leg ulcers, included during a six-month period. Twelve of the 46 patients
      (26%) (95% confidence limits: 14%-41%) had APC-resistance. APC-resistance is thus
      a common anticoagulant deficiency among venous leg ulcer patients and should be
      considered a risk factor for development of venous leg ulcer disease.

PMID- 9148536
TI  - [Intra-abdominal torsion of the testis with seminoma].
AB  - A 38-year-old man presented with acute onset of left iliac fossa pain. He had
      never noticed a left testis. An ultrasound scan showed a solid pelvic mass.
      Alfafoetoprotein and HCG were normal. Laparotomy for an acute abdomen was
      performed and revealed torsion of the left intra-abdominal testis. A left
      orchiectomy was performed. The patient made an uneventful recovery. Histology
      showed seminoma and carcinoma in situ. A testicular biopsy from the right testis
      showed no malignancy. A detailed examination of the genitalia should be part of
      the usual abdominal examination.

PMID- 9148538
TI  - [Cozaar (Losartan, MSD) and depression].

PMID- 9148537
TI  - [Bell's palsy treated with acyclovir].

PMID- 9148539
TI  - [Losartan (Cozaar) and depression].

PMID- 9148541
TI  - [Female infertility].

PMID- 9148540
TI  - [Cholesterol depression prevents heart disease].

PMID- 9148542
TI  - [Systemic antiviral chemotherapy].

PMID- 9148543
TI  - [Iodine intake in Denmark].
AB  - Iodine deficiency with a high frequency of goitre and, in severely affected
      areas, cretinism is common in some areas of the world. In Denmark the iodine
      intake as evaluated by urinary iodine excretion has been at a stable low level
      for many years, except for the part of the population now taking iodine
      supplementation as part of vitamin/ mineral preparations. The iodine intake is
      lowest in the western part of the country where an epidemiological study of
      elderly subjects has demonstrated a high frequency of goitre and hyperthyroidism
      in women. This supports the suggestion of a controlled moderate increase in
      iodine intake via an iodine supplementation program.

PMID- 9148544
TI  - [The management of back problems among the population. I. Contact patterns and
      therapeutic routines].
AB  - The aim of the study was to describe the professional meeting between back
      patients and health care providers seen from two points of view-the back patient
      and the health care provider. A questionnaire was presented to health care
      providers (general practitioners, physiotherapists, chiropractors, and
      specialists in rheumatology), in total 1018 health providers. A sample of the
      general population, 3204 individuals, were interviewed concerning their use of
      health care providers. Thirty-seven percent of the patients suffering from back
      trouble during the last 12 months consult a health care provider. The
      chiropractor sees eighteen times as many back patients as the general
      practitioner and nine times as many as the physiotherapist. General
      practitioners, physiotherapists, and chiropractors have different routines of
      practice, and the patients who consult the three provider groups have different
      sociodemographic and illness profiles.

PMID- 9148545
TI  - [The management of back problems among the population II. Therapists' and
      patients' perception of the disease].
AB  - The aim of the study was to describe how back trouble is interpreted by health
      care providers and a sample of the general population. Health care providers
      (general practitioners, physiotherapists, chiropractors, and specialists in
      rheumatology), in total 1018 professionals, filled out a mailed questionnaire. A
      sample of the general population, 3204 individuals, were interviewed concerning
      the interpretation of back trouble. Health care providers and the general
      population interpret a hypothetical episode of acute back trouble in different
      ways. Compared with the other provider groups and the general population,
      chiropractors to a higher degree classify back trouble as illness and a larger
      proportion would seek professional assistance. Both health care providers and the
      general population point out that back trouble is related to lack of physical
      fitness.

PMID- 9148546
TI  - [Percutaneous dilatation tracheostomy. A preliminary study].
AB  - Fifteen patients electively selected for percutaneous dilatational tracheostomy
      as performed with the Ciaglia Percutaneous Tracheostomy Introducer Set are
      reported in this preliminary study. The median time for insertion of the
      tracheostomy tube was 13.1 min. Complications were cuff puncture of the
      translaryngeal tube at an early stage of the procedure in one case, and minor
      bleeding controllable by the compressible effect of the dilatational procedure in
      three cases. During the posttracheostomy period complications included one case
      of minor bleeding controllable by digital compression and one case of minor
      infection, i.e. cellulitis in a few millimetres around the stoma without purulent
      secretion. Our preliminary results indicate that the technique as performed with
      the Ciaglia Introducer Set is effective and safe with only minor complications.
      Furthermore, we now use it as a bed-side procedure in the ICU, thus avoiding the
      transportation of critically ill patients to the operating theatre. A conclusion
      on the superiority of percutaneous tracheostomy to dissectional tracheostomy has
      to await clinical randomized studies including more patients.

PMID- 9148547
TI  - [Counting of axillary lymph nodes during surgery of breast cancer. A comparison
      between radiographic examination and pathological assessment].
AB  - Proper breast cancer surgery should include removal of at least ten axillary
      lymph nodes according to recommendations given by DBCG (The Danish Breast Cancer
      Group). The present study evaluated the results of counting the lymph nodes
      peroperatively on radiographs of the axillary tissue compared to the final
      pathological examination, the latter being considered the "gold standard". Since
      agreement between the two methods was found in only 66 out of 90 patients (Kappa
      value 0.279), we consider the peroperative radiological examination of the
      axillary fat to be of no practical value.

PMID- 9148548
TI  - [Yellow fever vaccination as prophylaxis of herpes labialis].
AB  - At some vaccination centres, it seems to be a clinical observation, that there is
      a reduction in the number of attacks of herpes labialis following yellow fever
      vaccination. We therefore conducted a double blind, prospective, randomized study
      to evaluate the efficacy of yellow fever vaccination against recurrent herpes
      labialis. Twenty-four patients with culture proven herpes labialis were allocated
      to either yellow fever vaccination or placebo (saline), with 12 persons in each
      group. After vaccination/ placebo the patients were followed for one year. The
      patients returned a letter every other month with information concerning the
      number of attacks during the period. Comparison of the data from the two groups
      after one year revealed no significant difference in the number of attacks
      between the two groups. In conclusion evaluation of the data from this study does
      not confirm the clinical observation that yellow fever vaccination may act as
      prophylaxis against herpes labialis.

PMID- 9148549
TI  - [Cigarette smoking further increases the risk of thrombosis in patients with mild
      hypertension].
AB  - Cigarette smoking and mild hypertension are well-recognized risk factors in the
      development of thrombotic vascular diseases. Enhanced platelet activity and
      reduced fibrinolytic activity has already been reported in patients with mild
      hypertension. This study demonstrated that cigarette smoking adds a further
      element of increased platelet activity to that already inherently present in
      hypertension: this could be an important factor promoting arterial thrombosis in
      hypertensive smokers.

PMID- 9148550
TI  - [Cerebral apoplexy--anticardiolipin antibody and factor V Leiden mutation].
AB  - A case of a twenty-nine year old woman with ischaemic stroke documented by
      Magnetic Resonance Imaging scanning is reported. As no embolic source was
      identified, it was most likely that the ischaemic stroke was caused by in situ
      arterial thrombosis. Except for a history of cardiovascular disease among her
      grandparents, she did not exhibit any of the classical risk factors for ischaemic
      stroke. Therefore, it is of interest that she had high serum concentrations of
      anticardiolipin antibodies and was a heterozygous carrier of the factor V Leiden
      mutation. It is possible that the combination of anticardiolipin antibodies and
      factor V Leiden mutation results in a procoagulant condition of the circulating
      blood, which in case of minor triggers may cause arterial occlusion. This
      mechanism may be responsible for the development of ischaemic stroke in the
      described case.

PMID- 9148551
TI  - [Follow up of the interdisciplinary researcgh program BIOTEK].

PMID- 9148552
TI  - [Nature medicine and hormonal side effects].

PMID- 9148553
TI  - [Breech presentation, vaginal delivery or cesarean section--a review article?].

PMID- 9148554
TI  - [Experimental development of a method of enzyme therapy in eye burns].
AB  - The proposed method of enzyme therapy of eye burns consists in instillations of a
      proteolytic drug for the first two days after burn and instillations of an
      antiproteolytic agent for the next 12 days. Experimental trials of the method in
      a rabbit with an alkaline burn of the cornea, including assessment of clinical
      manifestations of disease and investigation of the proteinase-inhibitor balance
      in the lacrimal fluid demonstrated a high efficacy of the new treatment.

PMID- 9148555
TI  - [Phenotype of peripheral blood lymphocytes of healthy donors and patients with
      corneal allotransplantation under conditions of hyperbaric oxygenation].
AB  - The purpose of this study was to elucidate the possible immunomodulating effect
      of hyperbaric oxygenation (HBO) on the immune status of patients with various
      ophthalmopathies and developing the graft-versus-host reaction after perforating
      keratoplasty. Surface phenotype of the peripheral blood lymphocytes was studied
      by two-color flow cytofluorometry in donors and patients with the rejection
      syndrome after transplantation of the cornea before and after a course of oxygen
      therapy. HBO exerted no immunodepressive effect, as judged from changes in the
      subpopulation composition (CD3+, CD4+, CD8+, CD16+, and CD56+) and expression of
      activation markers (CD25 and HLA-DR), in both patients and donors. The most
      probable explanation is that HBO effect on the immune system is indirect. On the
      other hand, from a clinical viewpoint the effect of HBO is undoubtedly positive,
      and hence, HBO exposure may be recommended for clinical application in
      transplantations of the cornea.

PMID- 9148556
TI  - [Evaluation of the effectiveness of endovascular laser irradiation of blood in
      multimodal treatment of retinal vein thrombosis].
AB  - A total of 189 cases with retinal vein thrombosis are analyzed. For 124 patients
      of these, the traditional therapy was supplemented with a course of endovascular
      laser exposure and 65 were treated traditionally. Analysis of the results of
      biochemical analyses showed that the level of medium-molecular plasma peptides
      and lipid peroxidation products was appreciably increased in such patients, and
      the balance in the system of cell proliferation inhibitors and stimulants is
      shifted. Endovascular laser exposure of the blood, added to the therapeutic
      complex for patients with retinal vein thromboses, helped attain better
      functional results and reduce the incidence of complications.

PMID- 9148557
TI  - [Visual evoked potentials in patients with refraction amblyopia in the presence
      of high myopia].
AB  - The informative value of a method for assessing the degree of amblyopia,
      developed by the author, was assessed in examinations of 16 children (29 eyes)
      with ametropic amblyopia caused by high myopia and 41 healthy controls. The
      method consists in recording the pattern-reversal visual evoked potentials (VEP)
      evoked by 4 patterns of different checksize and contrast. A relationship has been
      revealed between the VEP types detected by the proposed method and the degree of
      amblyopia (degree of vision acuity loss). The author came to a conclusion that in
      ametropic amblyopia, similarly as in stimulus deprivation amblyopia, changes of
      VEP develop that reflect the deterioration of contrast sensitivity function in
      low spatial frequencies. The developed VEP method with the modifications
      described in this paper may be useful in the diagnosis and objective evaluation
      of the degree of amblyopia.

PMID- 9148558
TI  - [Visual evoked potentials in infants in health and hypoplasia of the optic
      nerve].
AB  - Visual evoked potentials (VEP) in response to chess field reversion were studied
      in 29 infants aged from 6 weeks to 1.5 years with optic nerve hypoplasia and in
      healthy age-matched controls. Analysis of VEP in healthy children showed that the
      interval between weeks 6-9 and 16-20 of life was the period of their most rapid
      maturation, this making this period in the development of the optic system of man
      particularly significant. Three types of VEP disorders were detected in patients
      with optic nerve hypoplasia; these types correlate with the size of the optic
      disk and behavioral reactions of a child. Together with the clinical data, VEP
      may be used for assessing the function of the optic system of children with optic
      nerve hypoplasia and for early diagnosis of this disease.

PMID- 9148559
TI  - [Biomechanical regularities in the distribution of tension in various topographic
      zones of the eyelids in children in health and myopia of different degree].
AB  - The authors assessed the method for life-time study of the biomechanical
      characteristics of ocular tissues in 281 children (562 eyes) aged 7 to 14 years.
      The method for assessing the biomechanics of the eyelids is described. In detail.
      The rates of propagation of acoustic waves in normal tissue and in 1.0 to 6.0
      diopters myopia are presented. A correlation has been revealed between the
      increase of the velocity of acoustic surface waves, propagating in the horizontal
      direction in the internal segment of the orbital area of the upper eyelids, and
      the value of clinical refraction in myopia. The authors consider clinical signs
      of myopia-screwing up one's eyes and a wider lid slit-from a biomechanical
      viewpoint.

PMID- 9148560
TI  - [Significance of autoimmune reactions in the development of postoperative uveitis
      in patients with artificial lenses].
AB  - The levels of antibodies to native and denatured DNA in the blood were measured
      before and in the first days after extracapsular cataract extraction with
      implantation of intraocular lenses. Before surgery anti-DNA antibodies were
      appreciably more incident in patients with complicated cataracts in comparison
      with patients with senile cataracts (p < 0.01). A relationship was revealed
      between increased titers of anti-DNA antibodies before the operation and the
      development of "sterile" uveitis after it. On the whole, 50% of patients with
      increased titers of anti-DNA antibodies developed postoperative "sterile"
      uveitis. In patients with normal preoperative levels of these antibodies uveitis
      was observed in only 1.8% (p < 0.01). "Sterile" uveitis was arrested with
      steroids; if therapy was discontinued before antibody levels normalized, uveitis
      recurred.

PMID- 9148561
TI  - [Surgery of post-contusion dislocation intraocular syndrome].
AB  - The author discusses clinical variants of grave contusions of the eyeball
      involving the iridolenticular diaphragm and characterized by dislocation of the
      iris, lens, and vitreous body and subsequent development of secondary glaucoma.
      This condition is proposed to be singled out as the postcontusion dislocation
      intraocular syndrome. Sixty-four patients were treated. Variants of surgical
      repair are proposed, aimed at elimination of the dislocation and maximal repair
      of the anatomical ratios, including removal of the lens, vitrectomy, and
      iridoplasty with a circular pupil suture, depending on the severity of
      posttraumatic changes. Such treatment helped remove the retention disorders and
      prevent the irreversible changes; high ocular function was preserved in 41.7%
      patients and a good cosmetic effect attained in the rest cases. Remote results
      were followed up for up to 10 years. In only 8.3% patients they may be considered
      unsatisfactory.

PMID- 9148562
TI  - [Modeling of vitreoretinal proliferation].
AB  - Complexes of endogenous immunopeptides produced by autologous peripheral blood
      lymphocytes were injected to the vitreous body of 17 chinchilla rabbits (34
      eyes). The agents injected were autosupernatant. L fraction containing molecular
      substances with mol. weight of 40,000 to 60,000 D, and M fraction containing
      substances with mol. weight of 15,000 to 30,000 D. Clinical and morphologic
      studies demonstrated that injection of endogenous immunopeptides led to active
      lymphoid inflammatory infiltration associated with proliferation and formation of
      new vessels. In contrast to the M fraction, the exudative processes triggered by
      the L fraction were more definitely localized and associated with the appearance
      of fibroplastic cords (the proliferative component). The models created may be
      used for the development of methods for prevention and treatment of vitreoretinal
      proliferation.

PMID- 9148563
TI  - [Clinical, diagnostic and therapeutic aspects of congenital anophthalmos].
AB  - This study was aimed at elucidating the diagnostic potentialities of computer
      aided tomography (CAT) in congenital micro- and anophthalmia. Twenty-five young
      patients with various clinical manifestation of this abnormality were examined.
      Used in complex with the traditional diagnostic methods, CAT played the key role.
      It permitted imaging the entire complex of changes in the orbit and its contents,
      which helped choose adequate therapeutic measures. Surgical treatment was proven
      to be little effective or useless at all in cases with a more than 4 cm3 deficit
      of the orbital volume on the involved side; contrary to this, early staged
      fitting with prostheses is effective and creates favorable conditions for
      subsequent surgical correction in a less than 4 cm3 deficit of the volume.

PMID- 9148564
TI  - [Trends in the development of medical technology in ophthalmology].
AB  - Reviews ophthalmologic equipment designed in Russia and the former USSR countries
      in recent years. Groups the equipment by its purpose: diagnostic equipment,
      devices for investigating and training the visual functions, therapeutic and
      surgical equipment. The review is highly informative and describes in detail the
      devices presented.

PMID- 9148565
TI  - [Dynamic stereovisometry].
AB  - An original method of dynamic stereovisometry and a device for its realization
      Stereovisotest have been developed for examining the stereoscopic vision. Dynamic
      stereovisometry permitted the detection of positive and negative thresholds of
      stereoperception starting from the age of 4 years with an accuracy of 1 second of
      arc. The mean age-specific thresholds of stereoscopic vision were determined for
      a random sample of 1810 subjects aged 4 to 60 with binocular vision. For children
      aged 4 to 6 the mean threshold is 80 seconds of arc, in schoolchildren and
      adolescents it gradually reduces to 55 seconds of arc by the age of 16-20, from
      21 to 40 the threshold remains at the level of 45 seconds of arc, after which it
      starts to increase and reaches 60 seconds of arc by 60. Stereoscopic vision of
      subjects whose profession requires precise vision was examined and criteria for
      vision assessment offered. Training of stereoscopic vision using the
      Stereovisotest device were carried out. The possibility of raising the thresholds
      of stereoscopic perception to physiological ones has been demonstrated.

PMID- 9148566
TI  - [Use of cytostatics in multimodal treatment of glaucoma].

PMID- 9148567
TI  - [Intracapsular implantation of intraocular lenses in complicated cataracts].
AB  - A total of 75 patients with various types of cataracts, 35 of these (37 eyes)
      with complicated cataracts, were examined. Patients with a history of
      antiglaucoma surgery were not included in the study. Extracapsular extraction of
      complicated cataracts with intercapsular implantation and suture-free fixation of
      B. N. Alexeyev's IOL-IKB A004 were carried out after B. N. Alexeyev. The patients
      were examined using keratometry, ophthalmometry, visometry, echography and
      echobiometry, biomicroscopy, ophthalmoscopy, pupil test, tonometry, electron
      tonography, refractometry, gonioscopy, and entoptic phenomena. The results
      indicate the possibility of extracapsular cataract extraction with intracapsular
      implantation of IOLs after Alexeyev in patients with complicated cataracts. The
      incidence of intra- and postoperative complications in patients with complicated
      cataracts concomitant with myopia, glaucoma, uveitis, and diabetes mellitus did
      not differ from that in patients with uncomplicated cataracts concomitant with
      the same conditions. Moreover, the incidence of postoperative complications was
      far less in comparison with implantation of other lenses, as reported by some
      authorities.

PMID- 9148569
TI  - [Dynamics of ultrastructural morphology of the nucleolar apparatus in bovine
      preimplantation embryos collected in an area of chronic irradiation].
AB  - Ultrastructural morphology and immunoelectron microscopy of the nucleus and
      nucleologenesis in early preimplantation cow embryos were applied in an attempt
      to demonstrate a possible radiation injury to that early stage of development due
      to chronical irradiation of the animals in the Tchernobyl area. Mostly eight cell
      embryos as well as morulae were collected from superovulated cows which were
      previously constantly kept in zones of different levels of radioactive
      irradiation. In addition to the normometric status of reproductive organs in no
      case was it possible to detect an apparent deviation in the nuclear morphology or
      in the process of nucleologenesis as compared to the physiological situation
      (Kopecny et al., 1989b, 1991, 1996). This observation was supported by an
      immunoelectron microscope study of DNA association and penetration in the
      differentiated nucleolus in the late 8-cell stage. These observations show that
      the otherwise demonstrated radiation injury localized in the genome does not
      probably influence markedly the early events of the developing embryo and that
      the aberrant cytoplasmic command of the nuclear events known in other types of
      oocyte/early cow embryo impairment (review Kopecny and Nicmann, 1993; Kanka et
      al. 1991; Pavlok et al., 1993) is not seen in early embryos collected from
      chronically irradiated animals.

PMID- 9148568
TI  - [Experimental validation of using ozonized physiological solutions in intraocular
      infection].
AB  - The study was aimed at assessing the efficacy of ozonized normal salines in
      experimental endophthalmitis. Experiments demonstrated that, as the control group
      developed grave endophthalmitis and the clinical picture deteriorated by the end
      of experiment, eventuating in melting of tissues both in the anterior and
      posterior segments of the eye, in experimental animals, to which ozonized normal
      saline was administered directly after infection, endophthalmitis either did not
      develop at all or was less severe. The anterior segment of the eyeball was not
      involved in the infectious process, and the changes in the vitreous body were not
      so grave as in the controls, and by the end of experiment the inflammation ceased
      completely. By the end of the infectious process in the experimental group the
      majority of tissue structures of the posterior pole of the eyeball, including the
      retina, were retained. After administration of ozonized normal saline to animals
      with full-blood endophthalmitis the symptoms of the inflammatory process abated
      and the disease took a more favorable course than in control. Hence, experiments
      demonstrated that even a single intravitreal instillation of ozonized solution
      during an infectious process brings about a high prophylactic and therapeutic
      effect.

PMID- 9148570
TI  - [An epizootiologic study of an outbreak of equine influenza in the Czech Republic
      in the fall of 1995].
AB  - A mild outbreak of acute respiratory infection was reported in racing horses in
      the fall of 1995. Four studs were investigated for the sources and routes of
      infection. In five horses from two herds, virus isolates were obtained which, in
      preliminary typing experiments, were identified as the influenza A/equi 2 virus.
      The presence of this illness in all the examined herds was confirmed by a rise in
      specific antibody titres. The affected animals included both older vaccinated
      horses and young horses not yet vaccinated. Epidemiological studies suggested
      that the spread of infection occurred in situations where infected and non
      infected horses were together, most frequently at races. Newly infected horses
      brought the infection back to their studs where further animals became infected.
      Some of them, still being in the incubation period without any clinical signs,
      may have taken part in another race and passed the infection onto healthy animals
      from other studs. Since the races usually took place in 7-day intervals, the
      epidemiological chain remained continuous. The causes of the outbreak of
      infection in vaccinated horses are analysed. The length of post-vaccination
      immunity, the antigenic composition of vaccines and their completion with new
      strains of the influenza virus are discussed.

PMID- 9148571
TI  - [Isolation and identification of Lyssavirus strains from an area of Slovakia
      where oral antirabies vaccine was administered].
AB  - The study was aimed at isolation and subsequent identification of strains of
      rabies virus by means of monoclonal antibodies from foxes killed in the
      vaccination zone within the complex preliminary monitoring of oral antirabies
      vaccination. The results obtained indicate that the vaccines for oral antirabies
      vaccination used in Slovakia did not contain any vaccination strain pathogenic to
      the extremely sensitive target species-the fox (Vulpes vulpes).

PMID- 9148572
TI  - [The medical evacuation of the wounded and sick from the army to the hospital
      base at the front].

PMID- 9148573
TI  - [The prevention of influenza among the troops].
AB  - Peculiarities of modern influenza and other acute respiratory diseases in the
      units make medical service to execute epidemiologic supervision of these
      infections, especially in relation of newly formed collectives and troop
      contingency during there moving to other regions of the country. The medical
      service should apply agents of specific prophylaxis of influenza in groups of
      increased risk during threat of occurrence of an epidemic of influenza. It is
      necessary to contain a sufficient reserve of influenza vaccines for this purpose.
      At occurrence of pandemic strain of virus of influenza tactics and measures of
      prophylaxis should be revised with account of new epidemiologic situation.

PMID- 9148574
TI  - [The principles of rendering emergency care in bronchial asthma].

PMID- 9148575
TI  - [Transfusion therapy in acute blood loss (2)].

PMID- 9148576
TI  - [The graft-vs-host reaction in military transfusion treatment].

PMID- 9148577
TI  - [The ultrasonic study method in the diagnosis and treatment of abscesses and
      inflammatory infiltrates of the abdominal cavity].

PMID- 9148578
TI  - [The results of autogenic training in patients with ischemic heart disease after
      an aortocoronary bypass operation].
AB  - Were studied psychovegetative and somatic correlations in 115 patients with
      ischemic heart disease, having aortocoronary shunting operation and being at the
      sanatorium stage of the medical rehabilitation. To 70 patients was been carried
      out treatment with application of autogenous training (AT), to 45--without use of
      AT. The research has confirmed the presence in the patients psychological
      disadaptation, expressed essentially in asthenoneurotic and hypochondriac
      reactions. Is established, that estimation of expressiveness of emotional
      tension, investigated with the aid of Spilberger's psychometric scale, can be
      confirmed by parameters of peroxide oxidation of lipids and mathematical analysis
      of heart rythm. The use of variant of training modified by the authors has
      revealed improvement of clinical parameters, reflecting health state of the
      patients, which correlate with the data of the psychological test and the results
      of bicycle ergometry [correction of veloergometry].

PMID- 9148579
TI  - [Let us train future physicians on the experience of World War II veterans].

PMID- 9148580
TI  - [The structure of hospital infections in large hospitals].

PMID- 9148581
TI  - [The prophylactic efficacy of the trivalent polymer-subunit influenza vaccine
      Grippol (3)].

PMID- 9148582
TI  - [The social hygiene problems in preventing military job-related traumatism].

PMID- 9148583
TI  - [Preventive rehabilitative measures for preserving the health and occupational
      safety of flight personnel].
AB  - The existing concept of medical maintenance of flying personnel not takes into
      account the phase changes of functional condition and professional performance of
      a pilot. It causes the necessity of additional preventive rehabilitation,
      directed on restoration and preservation of important professional qualities of
      the pilots during the training and combat activity. The author offered reasonable
      system of rehabilitation measures, including indications, means and conditions of
      correction measures application. Is carried out practical introduction of
      preventive rehabilitation in system of medical maintenance of the Armed Forces of
      Ukraine. The data about its efficiency are given.

PMID- 9148584
TI  - [The organization of neurosurgical care on board submarines and surface ships of
      the Navy].

PMID- 9148585
TI  - [The certification of medical stores as the trend in enhancing quality].

PMID- 9148586
TI  - [From reminiscences of the war years].

PMID- 9148587
TI  - [Nobel laureates in the history of military medicine].

PMID- 9148588
TI  - [Prominent Soviet microbiologist and epidemiologist (on the centenary of the
      birth of V. M. Berman)].

PMID- 9148589
TI  - [Current problems in improving the technical equipping of the military medical
      service].

PMID- 9148590
TI  - [The continuity of the work of the hospital and the polyclinic].
AB  - The questions of continuity in "polyclinic-hospital" link in practical plan are
      decided not enough: there are not enough managing documents, are not developed
      the uniform indications to stationary treatment of scheduled patients and
      patients with urgent condition, are away uniform sights on structure and volume
      of operative interventions in polyclinic and hospital. There is no unification
      diagnostic standards, there are the distinctions in registration of the
      conclusions, that results the duplication of researches. Duration of expectation
      terms of hospitalization by number of fields patients remains dragged on. The
      integration in connection "polyclinic-hospital" requires the uniform
      installations on organization of treatment with use of standardized schedules,
      ordering of consulting, sharp planning of discharge and admission of the patients
      to the hospital, improvements of the medical documentation, strengthening of the
      organizing roles of the leader-clinicians, increase of professional preparation
      of the doctors, especially polyclinical link. The realization of an offered
      complex of the measures does not require any serious economic expenses.

PMID- 9148591
TI  - [Molecular defects of erythrocyte membrane proteins].

PMID- 9148592
TI  - [Dynamics of changes in the concentration of thyroid hormones in in rat blood
      after subtotal thyroidectomy, internal, or external irradiation].
AB  - Thyroidectomy or administration of high activities (> 1.1 Mbq) of 131I to rats
      causes initial decrease in blood concentration of thyroid hormones which returns
      to the normal level. Administration of lower doses (< 1.1 Mbq) of radioactive
      iodine or external radiation (1, 3, 6 Gr) did not cause similar changes. Data
      obtained that: 1) thyroid gland is relatively radioresistant organ with high
      reparative function after surgical or radioactive damage; 2) alterations of
      thyroid status after the external radiation are not related to a direct action of
      radiation on the thyroid gland.

PMID- 9148593
TI  - [Hypolipidemic effect of sulfated polysaccharides].
AB  - In experiments on hyperlipidemic rats it was observed the hypolipidemic effect of
      new sulfated polisaccharides-chitosan, lutelan and krilan sulfates, More
      pronounced decrease was established in VLDL and increase of HDL after sulfated
      polysaccharides treatment. The most distinct efficiency exhibites preparation
      with moledular mass of 20-40 x 10(3) D and the rate of sulfation 9-14%.

PMID- 9148594
TI  - [The study of the in vitro effect of selenium on formation of active oxygen
      species and lipid peroxidation in rat liver microsomes].
AB  - In vitro influence of sodium selenite on cytochrome P-450-dependent formation of
      active oxygen species on lipid peroxidation (LPO) in rat liver microsomes was
      studied. Sodium selenite (10(-6)-10(-3) M) did not influence rates of NADPH/Fe
      induced formation of active oxygen species (O2.-, OH., H2O2) and NAPDH-dependent
      LPO. Only at 10(-3) M selenite caused significant decrease in production of
      hydrogen peroxide in microsomes. Data obtained suggest that sodium selenite at
      physiological concentrations does not influence formation of active oxygen
      species by cytochrome P-450 and the rate of enzymatic LPO in rat liver
      microsomes.

PMID- 9148595
TI  - [In vitro effect of BITO preparation, ceruloplasmin, transferrin, and essentiale
      on the intensity of lipid peroxidation during thermal injury].
AB  - BITO decreased the intesity of lipid peroxdation; intensity of intravascular
      hemolyses at termal trauma. It increased oxidability of lipids of blood serum,
      liver and brain. Its antioxidative activity may be explainde by the presence of
      ceruloplasmin, posessing antioxidative activity may be explained by the presence
      of ceruloplasmin, posessing ascorbate oxidase, ferroxidase and superoxide
      dismutase activities. Lipid components of the fraction play a role of "structural
      antioxidants".

PMID- 9148596
TI  - [Effect of ethanol, diazepam, and reserpine on the activity of angiotensin
      converting enzyme and carboxypeptidase in normal state and during stress].
AB  - There was discovered a resemblance in the influence of some pharmacological
      agents such as ethanol, diazepam and rezerpine on the activity of enzymes of
      metabolism of biological active peptides in the blood under emotional stress. It
      was determined that the character of the influence depends on the emotional
      status of animals. The possibility of drawing both angiotensin converting enzyme
      and carboxypeptidase N in the stress-protection action of the ethanol, diazepam
      and rezerpine is discussed.

PMID- 9148597
TI  - [Activity of angiotensin-converting enzyme in the rabbit lacrimal fluid after
      burn of the cornea].
AB  - In the experimental model of severe alkaline burns of the rabbit cornea we found
      the dependence of angiotensin-converting enzyme activity in tears upon both the
      time periods and the degree of inflammation. It was indicated that the enzyme
      activity in tears of animals with ulceration of deep tissues of cornea was much
      higher than in tears of animals with surface erosion of cornea.

PMID- 9148598
TI  - [Metabolic changes in the rat liver during emotional stress].
AB  - Emotional stress of rats is accompanied by essential alterations in glycolysis
      and tricarboxylic acid cycle in the liver. These alterations were observed over a
      few days after the termination of stressor action. Perhaps it is one of the
      trigger mechanisms responsible for pathological changes in the organism.

PMID- 9148599
TI  - [Complex-formation between myeloperoxidase and fibronectin and its modulation by
      fibronectin ligands].
AB  - Human blood plasma fibronectin immobilised on agarose in physiological interacts
      with soluble myeloperoxidase (Kd = 2.43 mM). Interaction of myeloperoxidase with
      fibronectin adsorbed on immobilised gelatin a, natural fibronectin ligand,
      resulted in formation more stable complex (Kd = 0.94 mM). The presence of
      thermoaggregated (but not native) IgG in the liquid phase increased a stability
      of the complex (0.06 mM). It is suggested that myeloperoxidase could represent a
      component of complex super molecular structure, real immune complex.

PMID- 9148600
TI  - [Changes in glycolipid level in the brain of rats with different resistance to
      hypoxia during acclimation to cold].
AB  - Acclimation of rats to cooling (+3 C for 30 days) is accompanied by changes in
      the content of gangliozides, cerebrozides and sulfatides of brain during 6 hours,
      returned to the control level in next periods of acclimation. Changes in the
      content of sulfatides, and in smaller degree of cerebrozides and gangliozides
      depend from hypoxic stability of rats.

PMID- 9148601
TI  - [Possible use of erythrocyte antioxidant enzymes as markers of the course of
      disease in patients with hemoblastoses].
AB  - Blood and erythrocytes of 50 healthy volunteers and 105 patients with different
      forms of hemoblastoses were investigated. 54 patients had acute phase, 51
      patients--remission stage of disease. Essential differences in the activity of
      antioxidant enzymes (SOD, CAT, GSH-Px) were detected and compared with content of
      MDA and degree of anaemia. Acute phase had more significantly alteration of
      antioxidant defence: diverse changes of the activity of SOD and CAT,
      significantly inhibition of GSH-Px, the high level of MDA and increased degree of
      anaemia.

PMID- 9148602
TI  - [Autoantibodies against nerve tissue proteins long after cranio-cerebral injury].
AB  - 20 samples of serum of patients with remote consequences of brain trauma were
      tested to detect autoantibodies (a-AB) against brain proteins S-100 and NKP.
      Essential pathology was not found out by standard solid-phase immunoassay. The
      original method was used to detect a-AB to the whole complex of antigen
      determinants. Using this method the elevation of a-AB against S-100 and NKP was
      shown at 16 cases. The disturbance of idiotype-antiidiotype regulation was
      revealed at this group of patients. It is suggested that insufficient level of
      corresponding antiidiotypes creates the conditions for autoimmune aggressor of a
      AB against brain tissue.

PMID- 9148603
TI  - [Comparison of metabolism of water-soluble vitamins in healthy children and in
      children with insulin-dependent diabetes mellitus depending upon the level of
      vitamins in the diet].
AB  - Metabolism of vitamins C, B2, B6 and niacin in children with insulin-dependent
      diabetes mellitus was distinctly different from that of healthy persons of the
      same age as shown by studies of the correlation between content of vitamins or
      their coenzyme forms in blood, excretion of the vitamins with urine and content
      of the vitamins in a diet. These data corroborated once again that in estimation
      of the vitamins consumption suitable for ill children, the criteria of healthy
      children requirements for vitamins should not be taken into consideration.
      Dissimilar metabolism in healthy and impaired persons may also demonstrate some
      differences in consumption of these vitamins. Preliminary data showed that
      requirements of the impaired children for vitamin C were slightly increased, for
      vitamin B2--similar or slightly decreased as compared with healthy children.
      These results suggest that additional investigations are required for evaluation
      of vitamins consumption in children with diabetes mellitus of the I type.

PMID- 9148604
TI  - [Preparation of control human sera with increased level of certain classes of
      lipoproteins using serum fractions sedimented with sulfated polyanions].
AB  - Three main classes of human serum lipoproteins (LP), very low density
      lipoproteins (VLDLP), low density lipoproteins (LDLP), and high density
      lipoproteins (HDLP) were selectively sedimented by heparin and dextran sulfate in
      the presence of metal ions. These data were used for the development of a method
      for preparation of fractions of human serum enriched with certain class of LP.
      Using isolated fractions serums with increased content of total cholesterol,
      cholesterol of HDLP and triglycerides were prepared. These fractions may be used
      as control samples for evaluation of corresponding parameters in native samples.

PMID- 9148605
TI  - [Rapid isolation of 4-hydroxyphenylethanol from the bovine brain using Water Sep
      Pak Plus cartridges with lipophilic sorbent (Florisil)].
AB  - 4-Hydroxypherlylethanol, MAO-A Inhibitory component of endogenous MAO Inhibitory
      activity, tribulin, was isolated from a small quantity of bovine brain using
      Maters Sep-Pak Florisil cartridges. Procedure included isolation of crude
      tribulin fraction, which was passed through the cartridge. Preliminary data
      revealed that this substance is not absorbed on Florisil. The employment of this
      type of cartridges essentially accelerates isolation of 4-hydroxyphenyethanol
      from brain samples for quantitative determination. Pilot experiments also
      revealed that Sep-Pak Folrisil cartridges could be used for the rapid isolation
      of isatin, another endogenous MAO (B) inhibitor, from brain tissue.

PMID- 9148607
TI  - Electronic mail. A physician extender?

PMID- 9148606
TI  - [Tribulin--a novel endogenous monoaminoxidase inhibitor (dedicated to the memory
      of Merton Sandler)].
AB  - Tribulin is endogenous monoamine oxidase and benzidiazepine binding inhibitory
      activity extractable from biological tissues and body fluids into ethyl acetate.
      Tribulin output is increased in conditions of stress and anxiety. Several
      chemical components of tribulin have recently been identified. Isatin is a
      selective inhibitor of monoamine oxidase B. Esters of indoleacetic and 4
      hydroxyphenylacetic acids and 4-hydroxyphenyletanol selectively inhibit monoamine
      oxidase A. Biomedical importance of tribulin and its components is discussed.

PMID- 9148608
TI  - [Differential diagnosis and therapy of psoriatic arthritis].

PMID- 9148609
TI  - [New aspects on the morphology and pathogenesis of lupus erythematosus].

PMID- 9148610
TI  - [Histologic studies on leg veins in postthrombotic syndrome. Part II:vein wall
      injury].

PMID- 9148611
TI  - [A comparative analysis of monoamine oxidase activity in the tissues of the deep
      sea squid (Berryteuthis magister) and the mouse under normal and elevated
      atmospheric pressure].
AB  - The monoamine oxidase (MAO) from the liver of Comandor squid inhabiting at depth
      of 800 m transformed histamine along with specific substrates (tyramine,
      serotonin, benzylamine). MAO from the squid nervous ganglia as well as from mouse
      liver and brain was inactive towards histamine. Under normal atmospheric pressure
      the activity of the enzyme prepared from the squid frozen tissues was an order of
      10 lower than the enzymic activity revealed in fresh and previously frozen
      tissues of mouse brain and liver. Under 101 atm the squid tissue enzyme activity
      did not change whereas it decreased in mouse tissues. The distinctions in MAO
      sensitivity to high atmospheric pressure between land and deep-sea species is
      suggested to be due to both peculiar lipid composition of cell membranes and
      different structural features of the enzyme in the species investigated.

PMID- 9148612
TI  - [Amine oxidase from the bacterial strain Methanosarcina barkeri 27].
AB  - A new source of the enzyme amine oxidase (AO), namely bacteria of Methanosarcina
      barkery 27 strain, was discovered. The method AO isolation and purification from
      the bacteria was developed and the enzyme substrate and inhibitory specificity
      was studied. Contrary to some other microbial amine oxidases the AO investigated
      was shown to determine benzylamine and serotonin along with tyramine, all these
      substrates being deaminated at the equal rate. By contrast to other microbial AO
      the AO discovered was unable to deaminate histamine. The AO properties have been
      compared with those of mitochondrial monoamine oxidase from pig liver.

PMID- 9148613
TI  - [The repair of the membrane lipid bilayer in oxidative stress:
      phosphatidylethanolamine reacylation in synaptosome, photoreceptor and
      erythrocyte membranes].
AB  - The participation of unsaturated (linoleic and arachidonic) and saturated
      (palmitic) fatty acids in reacylation of phosphatidylethanolamine (PE) in
      synaptosomes, photoreceptor membranes and erythrocytes at oxidative stress was
      studied. Induction of lipid peroxidation (LPO) was found to result in a
      significant decrease in the content of PE polyenoic fatty acids due to their
      oxidative destruction. It might be related to both an activation of phospholipase
      A2 and a decrease in PE reacylation rate. On contrary, under the same conditions
      an increase in incorporation of palmitic acid into PE was observed. The results
      of this study suggest that phospholipid deacylation-reacylation reactions
      comprise an important mechanism of both protection and adaptation of organisms to
      oxidative stress.

PMID- 9148614
TI  - [Potential-gated currents in isolated spinal cord neurons of the river lamprey
      Lampetra fluviatilis].
AB  - Potential-gated currents in the membranes of enzymatically isolated neurons from
      the lamprey spinal cord were investigated using the whole cell variant of the
      patch-clamp technique. As it was revealed the main currents underlying action
      potential (AP) in the dorsal sensory cells as well as in branched cells are
      inward Na(+)- and outward K(+)-currents. Sodium current has the duration 4-9 ms,
      it was rapidly activated and inactivated and blocked by TTX. Its activation and
      inactivation processes can be fit to modified Bolzmann equations. Outward
      potassium current can be subdivided into at least two components: 1) early
      transient rapidly inactivated component which was sensitive to 4-AP and 2) later
      noninactivated more longer one which was sensitive to TEA. Their function as in
      the other neurons may be to repolarize membranes after AP generation and to
      provide the interval between APs during rhythmic activity. Ca2(+)-current was
      investigated using Ba2+ as a divalent carrier. Judging on two different values of
      the threshold there are two types of the Ca2(+)-channels in the membranes of the
      lamprey spinal cells. Ba2(+)-current depend not only on the voltage but on the
      intracellular enzyme systems particularly on the G-proteins, ATP and CP-CPK.
      Under normal conditions Ca2(+)-current activated during AP is small but it
      increase up to 5-10 nA when the other voltage-gated currents are blocked. We
      conclude that lamprey spinal neurons retain after isolation the electrical
      properties of neurons in the spinal cord. The obtained results have testified
      that the kinetic and pharmacological properties of the basic currents in the
      cells under study are close to those in the other vertebrate neurons and these
      cells are suitable for investigation of neurotransmitter, neuromodulator and
      pharmacological agents action on voltage- and agonist-gated membrane currents in
      vertebrate neurons.

PMID- 9148615
TI  - [The role of extracellular calcium in regulating the contraction of the
      developing musculature in the frog Rana temporaria].
AB  - Amplitude of both single and tetanic contractile responses of m. gastrocnemius
      (46th-51st stages of tadpoles Rana temporaria development) in contrast to those
      of myotomal muscle significantly reduced after decrease of extracellular calcium
      ion concentration. Such an effect was not observed on later stages. Adding of
      strontium ions instead of calcium did not recover contraction amplitude. Effects
      of such specific calcium ion channel antagonists as verapamil and nickel ions on
      contractions are not age-dependent indicating that contraction dependence on the
      number of exogenous calcium ions was not mediated by calcium channel functioning.
      The results demonstrate that system of electromechanical contact, provided by
      dihydropyridine receptors of tubular membrane, on the 46th-51st stages of tadpole
      development is already formed and functions as in mature muscles. It is suggested
      that contraction regulation in developing skeletal muscle can involve calcium
      ions which are linked to external surface of sarcolemma.

PMID- 9148616
TI  - [Age-related changes in the effect of catecholamines on spontaneous periodic
      motor activity in rat pups].
AB  - Reaction of spontaneous periodic motor activity (SPMA) to exogenous increase of
      catecholamine (CA) level in brain by means of L-DOPA injection or other methods
      of catecholaminergic system activation undergoes quite essential changes in
      process of early postnatal ontogenesis. Possible causes of such age changes are
      considered in present paper: 1) increase of SPMA reactivity to CA level change;
      2) heterochronic development of dopamine- and adrenergic systems; 3)
      heterochronia in maturation of SPMA activation and inhibition mechanisms; 4)
      maturation of its regulation levels. It was shown that activation of
      catecholamine systems resulted in changes of SPMA levels in the same direction as
      its natural age dynamics occurred: enhancement in growth period on the first week
      after birth, and subsequent decrease of activating and appearance of inhibitory
      effects in period of SPMA age inhibition.

PMID- 9148617
TI  - [The characteristics of the formation of the hypothalamo-hypophyseal
      neurosecretory system in the Arctic lemming Dicostonyx torquatus of Wrangel
      Island in the postnatal development period].
AB  - Hypothalamo-hypophyseal neurosecretory system (HHNS) of 1-30 days old lemmings
      Dicrostonyx torquatus from the Wrangel Island in the year of a decreased but
      still highly dense population was studied by paraldehyde fucshin method and
      immunohistochemically using antisera to vasopressin and oxytocin. In the period
      of first two weeks of postnatal development the rate of HHNS formation was found
      to have significant individual differences and to be slower than HHNS formation
      in laboratory rats due to less stable and suitable environmental conditions. Like
      in rats the rate of differentiation of the supraoptic nucleus in lemmings was
      faster than that of the paraventricular one. Formation of the median eminence was
      retarded as compared to the hypophyseal posterior lobe. Vasopressin-immunoactive
      structures appeared earlier than oxytocin-immunoreactive ones both in the
      neurosecretory centers and in the neurohaemal regions. By 21-30 days the
      development the HHNS system was practically completed and the levels of
      maturation of studied structures in different individuals became closer. In this
      period an accumulation of neurosecretory material was observed in all parts of
      the HHNS which is probably connected with activation of the system under the
      condition of stress due to a high population density.

PMID- 9148618
TI  - [Current achievements in the study of the signal mechanisms of the action of
      insulin and related peptides].

PMID- 9148619
TI  - [The types of interhemispheric interaction in man].

PMID- 9148620
TI  - [Physiological and biological problems of the microcirculation and their
      resolution in the evolution of the blood and blood circulation].

PMID- 9148621
TI  - [The interrelation of the phospholipid composition of the lungs in sheep and of
      the nematode Dictyocaulus filaria].
AB  - The effect of nematodes Dictyocaulus (D) filaria on phospholipid (PL) composition
      in the homogenate of sheep lungs has been demonstrated. The comparative analysis
      has shown no differences in the content and composition of PL in the lungs of
      healthy sheep and in nematodes. Infection of sheep by helminths was found to
      result in changes in the PL composition of sheep lungs. Thus, it is possible to
      conclude that D. filaria affecting structural and functional systems of the host
      causes changes in its PL content.

PMID- 9148622
TI  - [The choice of the methods for the surgical treatment of patients with cerebral
      arteriovenous malformations].
AB  - The paper analyzes the outcomes of surgical treatment made in 431 patients in
      1971-1994. Multimodality treatment for this abnormality was used, which reduced
      postoperative mortality.

PMID- 9148623
TI  - [Somatosensory evoked potentials in the assessment of cerebral ischemia in
      combined operations for intracranial aneurysms].
AB  - Combined surgery of extra-intracranial anastomosis (EICA) and occlusion of the
      afferent vessel by means of a balloon catheter was made in 14 patients with giant
      aneurysms of the internal carotid (IC) and middle meningeal artery (MMA). MMA was
      excluded without previously creating EICA in another patient. The purpose of the
      study was to define the informative value of a somatosensory evoked potential
      (SSEP) as an intraoperative criteria for possible permanent occlusion of the
      major vessel. In 9 patients, IC or MMA occlusion was shown to cause neither
      intraoperative SSEP changes no postoperative neurological defect. After IC
      occlusion one case showed 25% reductions in the SSEP amplitude, which was not
      followed by neurological deterioration. In another patient with IC occlusion, 40%
      decreases in the cortical response amplitude resulted in moderate postoperative
      hemiparesis. In one patient with transient IC occlusion, 50% falls in the SSEP
      amplitude were accompanied by poor EICA function, which made permanent IC
      occlusion be avoided. However, postoperative neurological defect progression was
      detected in 3 patients without intraoperative SSEP changes. The findings suggest
      that SSEP may be used to determine whether IC and MMA can be excluded at surgery
      for aneurysms. However, no intraoperative SSEP changes does not predict the
      constancy of a patient's neurological status.

PMID- 9148624
TI  - [The stereotaxic biopsy of tumors in the pineal area].
AB  - The outcomes of stereotactic biopsy (STB) of pineal tumors are presented. This
      diagnostic approach was applied in 51 patients aged 7 to 59 years (mean 23 years)
      and its main indication is to develop an adequate treatment policy by specifying
      the histological structure of a tumor. Informative morphological samples were
      taken in 42 (82%) cases. One patient died, another developed a persistent
      neurological defect after STB. A third of all cases was diagnosed as having
      germinomas and other 5 patients were found to have germinative cellular tumors of
      mixed structure, which reflects the views on the policy of examination and
      treatment of patients with pineal tumors and indications for the biopsy, which
      have been established at the N. N. Burdenko Institute of Neurosurgery, Russian
      Academy of Medical Sciences. In 14 cases, STB diagnosis was verified from 1 to 46
      weeks of postbioptic surgery connected with tumor removal or autopsy. There was
      100% coincidence in histological diagnosis. Indications for STB in patients with
      pineal tumors, the significance of its findings, methodological and technical
      aspects, as well as the clinical value of this diagnostic procedure are dealt
      with in the paper.

PMID- 9148625
TI  - [Intracranial endoscopic operations with ultrasonographic support in pediatric
      neurosurgery (the potentials and outlook)].
AB  - The outcomes of intracranial endoscopic operations for occlusive hydrocephalus
      (65 interventions in 60 children) and intracranial hematomas (11 operations in 10
      children) are analyzed. Indications and contraindications for intracranial
      endoscopic operations, equipment supply, specific features of their performance,
      and outcomes are discussed. In occlusive hydrocephalus, the outcomes were as
      follows: hydrocephalus stabilization (38%), complications (15%), mortality (3%),
      the follow-up lasting as long as 8 years. The dynamic evaluation of the
      intracranial status (clinical and sound monitoring) is the obligatory condition
      of intracranial endoscopic operations made for intracranial hematomas. There were
      no complications in children with intracranial hematomas after planned
      intracranial endoscopic operations. The application of flexible distal end
      controlled endoscopic, ultrasound-stereotactically aimed, and double-maneuver
      controlled systems (visual examination through the optic system of an endoscope
      in combination with intraoperative ultrasonographic monitoring) was shown to be
      optimal during intracranial endoscopic operations.

PMID- 9148626
TI  - [Positron-emission tomography in intracranial hematomas].
AB  - Positron emission tomography by using H2(15)O whose distribution in the brain
      reflects a genuine cerebral blood flow was made in 5 patients with suspected
      intracranial hematomas. It was shown that tunicary hematomas might be diagnosed
      by positron emission tomography. However, examination of cerebral blood flow was
      not optimal in this abnormality. Computerized tomography remains the basic method
      for diagnosing intracranial hematomas and positron emission tomography should be
      used to evaluate cerebral function.

PMID- 9148627
TI  - [60 years of the journal N. N. Burdenko Problems of Neurosurgery].

PMID- 9148628
TI  - [An analysis of the interconnections between the proliferative activity of benign
      and anaplastic astrocytomas of the cerebral hemispheres and their histological
      structural characteristics].
AB  - Studying the proliferative activity of 60 astrocytic gliomas in the cerebral
      hemispheres by immunohistochemical detection of proliferative nuclear antigen in
      their nuclei has revealed that the expression of this cancer proliferative marker
      statistically significantly differs in the labelling index of proliferative
      nuclear antigen in benign and anaplastic astrocytomas (5.2 and 34.7%,
      respectively). Analyzing the relationships between the proliferative activity of
      astrocytic gliomas to their histostructural features has ascertained that there
      are higher proliferative nuclear antigen labelling induces in the astrocytic
      gliomas along with mitotic figures, proliferation of the vascular endothelium,
      vesicle-shaped nuclear, and multinuclear cells, the two latter signs are of
      greater importance as they are much more frequently encountered. The above
      mentioned histological signs may be regarded as criteria for diagnosis of
      malignant transformation of astrocytomas.

PMID- 9148629
TI  - [A craniofacial approach to disseminated tumors of the anterior portions of the
      cranial base].
AB  - The authors have developed a modified craniofacial approach. Its essence is to
      extend a facial cut along the mid-forehead after Weber-Fergusson into the
      frontoparietotemporal region, by forming a common soft tissue craniofacial graft.
      The above access was used in 17 patients with benign tumors of the base of the
      skull, involved into the ethmoidal sinus, anterior cranial fossa, medial portions
      of one or both eye sockets, sphenoidal sinus, medial portions of one or both
      maxillary sinuses, nasal cavity, and nasopharynx. The use of this access
      increases the radical rate of removal of extended craniofacial tumors. The
      specific policy features of surgery and postoperative management.

PMID- 9148630
TI  - [A microsurgical method for treating the peripheral nerve trunk stump to prevent
      the phantom syndrome].

PMID- 9148631
TI  - [The use of the presigmoid-sinus approach for the removal of a neurinoma of the
      trigeminal nerve root].

PMID- 9148632
TI  - [The procedure for the surgical treatment of combined arteriovenous malformations
      and arterial aneurysms of the brain].
AB  - To choose the optimal surgical treatment, the follow-ups of 25 patients with
      arteriovenous malformations (AVMs) concurrent with arterial aneurysms who had
      been surgically treated were considered. Twenty four patients experienced
      spontaneous subarachnoidal hemorrhage, 16 of them were repeated and multiple. The
      accurate diagnosis of the source of bleeding was associated with objective
      difficulties. With allowance for intraoperative findings. AVMs caused hemorrhage
      in 14 (58%) cases, aneurysms in 6 (25%). AVMs and aneurysms in 4 (17%). Thirteen
      (52%) patients were operated on AVMs and aneurysms in one or two steps, 5 had
      operations only on aneurysms, 7, on AVMs alone. Taking into account ruptures and
      higher sizes of aneurysms after AVM dissection, it is concluded that it is
      necessary to immediately exclude saccular bifurcating aneurysms irrespective of
      the cause of bleeding. Possible variants of policy decisions are dealt with, by
      taking into account the specific features of the location of AVMs and aneurysms
      the sources of hemorrhage. One-stage surgical interventions into AVMs and
      aneurysms are recognized to be optimal.

PMID- 9148633
TI  - [The Pallister-Hall syndrome--a rare case and an example of the differentiated
      approach to the treatment of hormonally inactive hypothalamic hamartomas].

PMID- 9148634
TI  - [A short essay on the history of the A. D. Romodanov Institute of Neurosurgery of
      the Academy of Medical Sciences of Ukraine].

PMID- 9148636
TI  - Congress Orthopaedica Belgica. Leuven, 6-8 September 1995. Proceedings and
      abstracts.

PMID- 9148635
TI  - [Temporary preventive clipping of the major brain arteries in the surgical
      treatment of arterial aneurysms].
AB  - Preventive temporary clipping of the carrying arteries reduces the incidence of
      intraoperative hemorrhage in anterior connecting arterial aneurysms from 26 to
      13%, in middle cerebral arterial arterial aneurysms from 29 to 4%. In anterior
      connecting arterial aneurysms, the use of preventive temporary clipping of the
      carrying arteries fails to affect surgical outcomes. In middle cerebral arterial
      arterial aneurysms, this procedure decreases postoperative mortality from 17 to
      12% by reducing the incidence of intraoperative hemorrhage; however, the rates of
      disability due to possible brain ischemia in the middle cerebral arterial bed
      rates increases from 32 to 40%.

PMID- 9148637
TI  - [Radiological study of the migration of prosthetic implants following hip
      arthroplasty].
AB  - Migration of the acetabular and femoral implants after THR is a better index of
      the stability of the bone-implant interfaces than are clinical or radiological
      results. Roentgenstereophotogrammetry (RSA) studies 3-D migration of the implants
      with high accuracy (0.15 to 0.28 mm for linear migrations). RSA presents several
      drawbacks which restrict its use to prospective studies on small numbers of
      patients. Simpler methods have therefore been developed to assess 2-D migration
      on standard films in retrospective studies. The precision of these "simple"
      methods is limited, due to several factors: the difficulty to define reliable
      landmarks on femur or pelvis, sometimes even on implants, measurement errors,
      related to variations in radiographic technique (focal distance, beam centering,
      patient positioning). Sutherland, Wetherell and Nunn have proposed methods with
      an accuracy around 2-3 mm. It appears impossible to correct migration
      measurements for distorsions due to patient positioning; the EBRA method was
      therefore developed to reject non-comparable films using a comparability
      algorithm. A precision of 0.20 to 0.32 mm can thus be reached for the study of
      cup migration. The same pitfalls are encountered in assessment of migration of
      the femoral implant; a preliminary theoretical study is mandatory for every
      implant studied. The data presently available show that migration at 2 years is
      predictive of the long-term evolution of an implant; for the cup, migration of 1
      mm or more at 2 years is predictive of late failure, and similar conclusions can
      be drawn regarding the femoral implant. The 2-D assessment of implant migration
      using a correct "simple" method provides a mean to evaluate a new implant or an
      innovative technical modification in a reasonable amount of time, on a limited
      number of patients.

PMID- 9148638
TI  - [Isometric reconstruction of the anterior cruciate ligament. Determination of the
      femoral and tibial tunnels].

PMID- 9148639
TI  - [Biomechanics of the normal elbow and following total semi-constrained
      arthroplasty].
AB  - The elbow possesses two degrees of freedom: flexion-extension and pronation
      supination. The axis of flexion-extension joins the centers of the capitellum and
      of the trochlea. The axis of pronation-supination passes through the head of the
      radius, and through the distal ulnar dome. The functional elbow mobilities
      include 100 degrees of elbow flexion (30 to 130 degrees) and 100 degrees of
      forearm rotation (50 degrees of pronation and 50 degrees of supination). The
      elbow is submitted to high articular contact forces. The joint stability depends
      on the articular surfaces, capsulo-ligamentous restraints and dynamic muscular
      contractions. As a practical application of this fundamental knowledge, an
      experimental study of the effects of total elbow arthroplasty on joint stability
      and muscle moment arms is reported, insisting on the deleterious effects of
      implant malpositioning.

PMID- 9148640
TI  - [Complications of supracondylar fractures of the humerus in children].
AB  - The supracondylar fracture of the humerus is the commonest type of elbow fracture
      in children. The peak incidence for this injury is between 5 and 10 years of age.
      The complications of these displaced fractures remain challenging problems. The
      early complications are mostly the neuro-vascular injuries. The difficulty in
      maintaining the reduction and ultimately the cubitus varus is the most frequent
      long-term complication with an incidence ranging from 3 to 57%. Adequate
      reduction and pinning has dramatically decreased this incidence. This paper
      describes these complications and their treatments.

PMID- 9148641
TI  - [Retrospective analysis of 78 surgically repaired fractures of the radial head].
AB  - The authors present a analysis of 78 cases of radial head fracture operated in
      the same department. 16 cases were added to the first study of 62 cases operated
      between 1967 and 1988 and published in 1991. According to the Mason
      classification modified by Morrey, there were 22 type II, 24 type III and 32 type
      IV. Surgical treatment consisted in an osteosynthesis in 35 cases, a fracture
      fragment excision in 9 cases, a resection of the head in 24 cases, a silastic
      prosthesis in 10 cases. The results have been studied on a functional and
      radiological basis with follow-up from 2 to 23 years (mean 5 years). The authors
      noted the good results of the type II fractures which had an osteosynthesis, the
      satisfactory results in more than 50% of the cases with resection of the radial
      head. The comparison of both series established the absence of prosthesis in the
      recent one. The poor results of the comminutive fractures with elbow dislocation
      lead the authors to consider the prothesis in these fractures, as a possible
      indication.

PMID- 9148643
TI  - Aldehyde dehydrogenase genes.

PMID- 9148642
TI  - Alcohol dehydrogenases.

PMID- 9148644
TI  - Proceedings of the 1st Asia Pacific Symposium on Cochlear Implant and Related
      Sciences. Kyoto, Japan, April 3-5, 1996.

PMID- 9148645
TI  - [Perennial rhinitis: antihistaminic and anti-inflammatory treatment].
AB  - The use of various medications in chronic rhinitis in children is discussed.
      Evastin has been shown to eliminate histamine papules in 93% of cases and those
      caused by D. pteronyssinus in 68% of cases. After 10 days of treatment,
      conjunctival response decreased or disappeared in 80% of cases and nasal response
      decreased in 69%. Clinically, evastin was effective in 14 of 22 children and
      produced moderate effects in 2 and no effect in 6. There were no dropouts because
      of problems of tolerance. In a preliminary study of intranasal azelastin in 21
      children with chronic allergic rhinitis, clinical improvement was significant.
      Various multicenter trials are reported, focusing on those using fluid
      budesonide. Both medications were effective in reducing symptoms and the
      antihistamine effect usually was earlier. There were no differences between
      medications as evaluated by nasal challenge or tolerance. Finally, budesonide was
      used in 13 patients for 4 months. Nasal obstruction and secretion improved, and
      rhinomanometry results improved significantly.

PMID- 9148646
TI  - Determination of ultratrace amounts of copper (II) by its catalytic effect on the
      oxidative coupling reaction of 3-methyl-2-benzothiazolinone hydrazone with N
      ethyl-N-(2-hydroxy-3-sulfopropyl)-3,5-dimethoxyaniline.
AB  - A spectrophotometric method was developed for the determination of ultratrace
      amounts of copper(II) based on its catalytic effect on the oxidative coupling
      reaction of 3-methyl-2-benzothiazolinone hydrazone with N-ethyl-N-(2-hydroxy-3
      sulfopropyl)-3,5-dimethoxyaniline to produce an intensely coloured dye
      (lambda(max) = 525 nm) in the presence of hydrogen peroxide. In this reaction,
      pyridine acted as an effective activator for the catalysis of copper(II). By
      measuring the absorbance of the dye, copper(II) can be determined at the 0.002
      0.1 ng cm(-3) (3.1 x 10(-11)-1.6 x 10(-9) mol dm(-3) level. The relative standard
      deviation for ten determinations of 0.06 ng cm(0-3) of copper(II) was 2.6%. The
      proposed method was successfully applied to the determination of copper(II) in
      tap water and biological material.

PMID- 9148647
TI  - Clarifying the direct relation between total cholesterol levels and death from
      coronary heart disease in older persons.
AB  - BACKGROUND: The importance of total cholesterol level as a risk factor for
      coronary heart disease in older adults is controversial. OBJECTIVE: To determine
      whether findings showing that total cholesterol level is not an important risk
      factor for coronary heart disease in older adults are the result of inadequate
      adjustment for co-occurring diseases and frailty. DESIGN: Multicenter,
      longitudinal study with 5-year follow-up for death. PARTICIPANTS: 4066 men and
      women from East Boston, Massachusetts; Iowa and Washington counties, Iowa; and
      New Haven, Connecticut. MEASUREMENTS: In 1988, participants were interviewed
      about their health status and had blood samples taken. Mortality follow-up was
      through 1992. RESULTS: In analyses that included all fatal coronary heart disease
      events (252 deaths) and did not adjust for risk factors for coronary heart
      disease and measures of frailty, persons with the lowest total cholesterol levels
      (< or = 4.15 mmol/L [< or = 160 mg/dL]) had the highest rate of death from
      coronary heart disease, whereas those with elevated total cholesterol levels (>
      or = 6.20 mmol/L [> or = 240 mg/dL]) seemed to have a lower risk for death from
      coronary heart disease (P for trend = 0.04). After adjustment for established
      risk factors for coronary heart disease and markers of poor health (including
      chronic conditions, low serum iron and albumin levels) and exclusion of 44 deaths
      from coronary heart disease that occurred within the first year, elevated total
      cholesterol levels predicted increased risk for death from coronary heart
      disease, and the risk for death from coronary heart disease decreased as
      cholesterol levels decreased (P for trend = 0.005). CONCLUSIONS: Elevated total
      cholesterol level is a risk factor for death from coronary heart disease in older
      adults, and the apparent adverse effects associated with low cholesterol levels
      are secondary to comorbidity and frailty. This suggests that excluding older
      persons from cholesterol screening is inappropriate, but interpretation of
      screening results in older persons requires clinical judgment. Results from
      controlled clinical trials are needed to clarify this issue.

PMID- 9148648
TI  - Effect of antihypertensive drug treatment on cardiovascular outcomes in women and
      men. A meta-analysis of individual patient data from randomized, controlled
      trials. The INDANA Investigators.
AB  - BACKGROUND: Trials of drug therapy for hypertension have shown that such therapy
      has a clear overall benefit in preventing cardiovascular disease. Although these
      trials have included slightly more women than men, it is still not clear whether
      treatment benefit is similar for both sexes. OBJECTIVE: To quantify the average
      treatment effect in both sexes and to determine whether available data show
      significant differences in treatment effect between women and men. DESIGN:
      Subgroup meta-analysis of individual patient data according to sex. Analysis was
      based on seven trials from the INDANA (INdividual Data ANalysis of
      Antihypertensive intervention trials) database and was adjusted for possible
      confounders. PATIENTS: 20,802 women and 19,975 men recruited between 1972 and
      1990. INTERVENTIONS: Primarily beta-blockers and thiazide diuretics. RESULTS: In
      women, treatment effect was statistically significant for stroke (fatal strokes
      and all strokes) and for major cardiovascular events. In men, it was
      statistically significant for all categories of events (total and specific
      mortality, all coronary events, all strokes, and major cardiovascular events).
      The odds ratios for any category of event did not differ significantly between
      men and women. In absolute terms, the benefit in women was seen primarily for
      strokes; in men, treatment prevented as many coronary events as strokes.
      Graphical analyses suggest that these results could be completely explained by
      the difference in untreated risk. CONCLUSIONS: In terms of relative risk,
      treatment benefit did not differ between women and men. The absolute risk
      reduction attributable to treatment seemed to depend on untreated risk. These
      findings underline the need to predict accurately the untreated cardiovascular
      risk of an individual person in order to rationalize and individualize
      antihypertensive treatment.

PMID- 9148649
TI  - Elastance of the pleural space: a predictor for the outcome of pleurodesis in
      patients with malignant pleural effusion.
AB  - BACKGROUND: In patients who have malignant pleural effusion, it is difficult to
      diagnose trapped lung before thoracoscopy, thoracostomy, and drainage of the
      effusion. Predicting the outcome of pleurodesis in patients who have malignant
      pleural effusion without trapped lung is also difficult. OBJECTIVE: To
      investigate the factors that may be useful in diagnosing trapped lung and
      predicting the outcome of pleurodesis. DESIGN: Prospective cohort study. SETTING:
      University medical center. PATIENTS: 65 patients with symptomatic malignant
      pleural effusion. INTERVENTION: A chest tube was inserted for drainage of the
      effusion, and pleurodesis was done using bleomycin as the sclerosant.
      MEASUREMENTS: The pH and glucose levels of the effusion and the elastance of the
      pleural space (defined as the decline in pleural fluid pressure in cm H2O after
      removal of 500 mL of effusion) were measured. The outcome of pleurodesis was
      evaluated 1 month after the chest tube was removed. RESULTS: Patients with an
      elastance of 19 cm H2O or more had a higher incidence of trapped lung (11 of 14
      patients) than did those with an elastance less than 19 cm H2O (3 of 51 patients)
      (P < 0.001). None of the 14 patients with an elastance of 19 cm H2O or more and
      none of the 14 patients with a trapped lung had successful pleurodesis. Forty-two
      of 43 patients with an elastance less than 19 cm H2O who did not have a trapped
      lung had successful pleurodesis. Elastance seemed to be the best predictor for
      trapped lung and outcome of pleurodesis, although outcome was also correlated
      with pH and glucose levels of the effusion. Low-dose bleomycin (30 mg) is as
      effective as the usual dose of bleomycin (60 mg) for pleurodesis. CONCLUSION: In
      patients with symptomatic malignant pleural effusion, measurement of the
      elastance of the pleural space is a simple and effective method for the diagnosis
      of trapped lung and prediction of the outcome of chemical pleurodesis with
      bleomycin.

PMID- 9148650
TI  - Diagnostic utility of ultrasonography of leg veins in patients suspected of
      having pulmonary embolism.
AB  - BACKGROUND: The standard diagnostic approach in patients suspected of having
      pulmonary embolism starts with perfusion-ventilation lung scanning. If the
      resulting scan is not diagnostic, pulmonary angiography should be done. The use
      of tests for deep venous thrombosis has been advocated as an adjunct to
      establishing the diagnosis of pulmonary embolism, but no prospective studies have
      provided adequate information about the value of these tests. OBJECTIVE: To
      determine the accuracy and potential clinical utility of compression
      ultrasonography in the diagnosis of pulmonary embolism. DESIGN: Prospective
      cohort study with blinded assessment of ultrasonographic results. SETTING:
      Teaching hospital. PATIENTS: 397 consecutive inpatients and outpatients in whom
      pulmonary embolism was clinically suspected. MEASUREMENTS: Sensitivity and
      specificity of compression ultrasonography. Perfusion-ventilation scanning and
      angiography were the conjoint gold standard for determining the presence or
      absence of pulmonary embolism. Also calculated were the number of angiograms and
      lung scans avoided and the number of patients unnecessarily treated when
      compression ultrasonography was included in the diagnostic strategy. RESULTS: The
      overall sensitivity of compression ultrasonography for deep venous thrombosis in
      patients with pulmonary embolism was 29% (95% CI 22% to 37%); the specificity was
      97% (CI, 94% to 99%). Adding ultrasonography to the diagnostic approach before
      lung scanning would avoid approximately 14% of lung scans and 9% of angiograms
      but would lead to unnecessary treatment of 13% of patients who have an abnormal
      ultrasonographic result (2% to 4% of all those receiving anticoagulation). When
      compression ultrasonography is done only in patients with a nondiagnostic lung
      scan, 9% of angiographies are prevented at the cost of unnecessarily treating 26%
      of patients who have an abnormal ultrasonographic result (2% of all patients
      receiving anticoagulation). CONCLUSION: The diagnostic value of compression
      ultrasonography for the detection of deep venous thrombosis in patients suspected
      of having pulmonary embolism is limited; the gain in diagnostic efficiency
      obtained through the use of ultrasonography may be offset by a loss in diagnostic
      accuracy.

PMID- 9148651
TI  - Intravenous iron and erythropoietin for anemia associated with Crohn disease. A
      randomized, controlled trial.
AB  - BACKGROUND: Anemia often complicates Crohn disease and affects quality of life.
      OBJECTIVE: To evaluate the efficacy of intravenous iron alone and in combination
      with erythropoietin for the treatment of anemia associated with Crohn disease.
      DESIGN: Double-blind, randomized, placebo-controlled trial with a subsequent open
      label phase. SETTING: University-based gastroenterology outpatient clinic.
      PATIENTS: 40 patients with Crohn disease and a hemoglobin concentration of 10.5
      g/dL or less. INTERVENTION: All patients received intravenous iron saccharate for
      16 weeks. During the blinded phase of the trial, they received either
      erythropoietin or placebo. During the open phase, the erythropoietin dose was
      increased in non-responders who had received erythropoietin and erythropoietin
      therapy was initiated in nonresponders who had received placebo. MEASUREMENTS:
      Response was defined as an increase in hemoglobin concentration of 2 g/dL or
      more. RESULTS: 15 of 20 patients in the placebo group (75% [95% CI, 51% to 91%])
      and 18 of 19 patients in the erythropoietin group (95% [CI, 74% to 100%])
      responded to intravenous iron (P = 0.20). The erythropoietin group had a higher
      cumulative response rate (P = 0.036) and a more pronounced mean increase in
      hemoglobin concentration (4.9 g/dL in the erythropoietin group compared with 3.3
      g/dL in the placebo group, a difference of 1.6 g/dL [CI, 0.6 g/dL to 2.5 g/dL]; P
      = 0.004). In the open phase, all 6 previous nonresponders had a response.
      Hematologic response was associated with improved quality of life (P = 0.03).
      CONCLUSIONS: Most patients who have anemia associated with Crohn disease respond
      to intravenous iron alone. Erythropoietin has additional effects on hemoglobin
      concentrations.

PMID- 9148652
TI  - Termination of implantable pacemaker therapy: experience in five patients.
AB  - BACKGROUND: Established guidelines direct the initial implantation of permanent
      pacemakers. Elective replacement of these devices is common. However, no
      guidelines exist for the removal of permanent pacemakers and the termination of
      long-term cardiac pacing. OBJECTIVE: To describe the feasibility and safety of
      terminating cardiac pacing in carefully selected patients. DESIGN: Case series.
      SETTING: University hospital. PATIENTS: Five adults with permanent pacemakers who
      were referred for pacemaker replacement or a complication related to cardiac
      pacing. All patients showed alleviation or reversal of the electric disturbance
      that originally led to the implantation of the device. The patients had received
      a pacemaker for a class I or II indication (that is, symptomatic bradycardia or
      asymptomatic, persistent third-degree atrioventricular block at the level of the
      atrioventricular node). INTERVENTION: After an appropriate natural rhythm was
      documented, pacemakers were removed from all patients. MEASUREMENTS: Time without
      recurrence of symptomatic bradycardia. RESULTS: No patient had recurrent
      symptomatic bradycardia after 18 to 48 months of clinical follow-up. CONCLUSIONS:
      The presence of a permanent pacemaker does not necessarily imply a permanent need
      for cardiac pacing. Discontinuation of cardiac pacing may be considered in
      certain patients. Establishing consensus criteria about the potential
      indications, methods, and timing of the termination of cardiac pacing seems
      appropriate.

PMID- 9148653
TI  - Medicinal applications of delta-9-tetrahydrocannabinol and marijuana.
AB  - The use of crude marijuana for herbal medicinal applications is now being widely
      discussed in both the medical and lay literature. Ballot initiatives in
      California and Arizona have recently made crude marijuana accessible to patients
      under certain circumstances. As medicinal applications of pure forms of delta-9
      tetrahydrocannabinol (THC) and crude marijuana are being considered, the most
      promising uses of any form of THC are to counteract the nausea associated with
      cancer chemotherapy and to stimulate appetite. We evaluated the relevant research
      published between 1975 and 1996 on the medical applications, physical
      complications, and legal precedents for the use of pure THC or crude marijuana.
      Our review focused on the medical use of THC derivatives for nausea associated
      with cancer chemotherapy, glaucoma, stimulation of appetite, and spinal cord
      spasticity. Despite the toxicity of THC delivered in any form, evidence supports
      the selective use of pure THC preparations to treat nausea associated with cancer
      chemotherapy and to stimulate appetite. The evidence does not support the
      reclassification of crude marijuana as a prescribable medicine.

PMID- 9148654
TI  - The man with stars inside.
AB  - Public opinion polls show that a large percentage of persons in the United States
      currently favor the legalization of professionally assisted death. This support
      reflects widespread fear and confusion over the tortuously prolonged and painful
      process of dying countenanced by contemporary medicine. Physician-assisted
      suicide and euthanasia are complex moral issues. The current drive to translate
      them into debates about "rights" and public policy is curious: Does the energy
      directed toward "palliation-by-death" mean that our society is more compassionate
      now, or more just, than in the past? To the contrary, I believe that the movement
      toward assisted death reflects inadequate palliative care, poor patient-physician
      communication, great confusion about the right to refuse treatment, and profound
      inequity in U.S. health care. Legalization of assisted death diverts us from
      addressing these problems. Palliation-by-death will drive us farther apart, not
      closer together.

PMID- 9148655
TI  - Workforce reform, international medical graduates, and the in-training
      examination.

PMID- 9148656
TI  - Liver transplantation and hepatitis B.

PMID- 9148657
TI  - Suggested technique for fecal occult blood testing and interpretation in
      colorectal cancer screening. American College of Physicians.

PMID- 9148659
TI  - The making of a public health physician.

PMID- 9148658
TI  - Screening for colorectal cancer with the fecal occult blood test: a background
      paper. American College of Physicians.
AB  - PURPOSE: Screening for colorectal cancer with fecal occult blood tests or
      sigmoidoscopy can reduce mortality rates. If occult blood testing is done,
      clinicians must decide how to interpret the results and plan further management.
      If the results are positive, a decision must be made about evaluating the colon.
      This report provides information that can be used to perform fecal occult blood
      tests, interpret the results of those tests, and plan patient management. DATA
      SOURCES: The MEDLINE database was searched for data relevant to optimizing the
      technique of fecal occult blood testing. Studies were also identified from the
      bibliographies of published articles about test performance and the
      interpretation of test results, particularly sensitivity, specificity, and the
      probability of colorectal cancer after a positive test result. STUDY SELECTION
      AND DATA EXTRACTION: Studies were selected and data were extracted on the basis
      of the authors' combined judgment. DATA SYNTHESIS: When used for screening, fecal
      occult blood tests have positive results about 1% to 16% of the time, depending
      on such factors as the age of the person being tested, whether the sample is
      rehydrated, and whether the test is used for initial screening or for
      rescreening. When the colons of persons who have positive test results are
      evaluated, the rate of finding any colorectal cancer is about 2% to 17% and the
      rate for early colorectal cancer (Dukes stage A or B) is about 2% to 14%.
      CONCLUSIONS: These results suggest that, in general, persons who have positive
      results on a fecal occult blood test should have a full colonic examination. More
      research is needed to understand and improve the sensitivity and specificity of
      the fecal occult blood test.

PMID- 9148660
TI  - Anthracycline-induced cardiotoxicity.

PMID- 9148661
TI  - Anthracycline-induced cardiotoxicity.

PMID- 9148662
TI  - Reliability of angiotensin-converting enzyme gene polymorphism in testing.

PMID- 9148663
TI  - Interferon-alpha treatment and formation of factor VIII antibodies.

PMID- 9148664
TI  - Interferon-alpha treatment and formation of factor VIII antibodies.

PMID- 9148665
TI  - Gram-positive infections and quinolones in neutropenia.

PMID- 9148667
TI  - Acyclovir plus steroids for herpes zoster.

PMID- 9148666
TI  - Gram-positive infections and quinolones in neutropenia.

PMID- 9148668
TI  - Acyclovir plus steroids for herpes zoster.

PMID- 9148669
TI  - Acyclovir plus steroids for herpes zoster.

PMID- 9148670
TI  - Prognostic model for primary melanoma.

PMID- 9148671
TI  - Response to activated protein C and cerebrovascular disease.

PMID- 9148672
TI  - Allergic reaction to varicella vaccine.

PMID- 9148673
TI  - Reversing idiopathic dilated cardiomyopathy with growth hormone: is this
      possible?

PMID- 9148674
TI  - Refractory postpartum anemia due to vitamin B6 deficiency.

PMID- 9148675
TI  - Autosomal/recessive hypocalciuric hypercalcemia.

PMID- 9148676
TI  - Quality comes home.

PMID- 9148677
TI  - A library for internists IX. Recommendations from the American College of
      Physicians.

PMID- 9148678
TI  - [Usefulness and limits of intraoperative hormone determination in the surgery of
      endocrine duodeno-pancreatic tumors. Experience of 74 cases].
AB  - 74 patients underwent surgery for organic hyperinsulinism (51 cases) or for
      Zollinger-Ellison syndrome (23 cases). 20 minutes after removal of the specimen,
      quick intra-operative hormone measurements were done in the systemic and portal
      blood as well, with intra-operative secretin stimulation test for gastrinoma(s),
      to assess completeness of surgery. Results accurately predicted cure (all
      insulinomas) or non-cure (half of gastrinomas) of the disease. Stumbling-blocks
      of the method are: a) the possibility of normal hormone base line levels at the
      time of surgery; b) the importance of secretion of proinsulin products by
      insulinomas. Those products are not taken in account by the modern assay
      technique with monoclonal antibodies (IRMA). Basal and stimulated portal
      measurements are more sensitive than measurements in the systematic blood.

PMID- 9148679
TI  - Regulation of surgical smoke plume.

PMID- 9148680
TI  - Barriers to and facilitators of research utilization in perioperative nursing
      practice.

PMID- 9148681
TI  - Biocatalysis-95. Proceedings of the International Conference. Suzdal, Russia,
      August 28-September 1, 1995.

PMID- 9148682
TI  - Biochemical and phylogenetic characterization of two novel deep-sea Thermococcus
      isolates with potentially biotechnological applications.
AB  - The partial 16S rDNA gene sequences of two thermophilic archaeal strains, TY and
      TYS, previously isolated from the Guaymas Basin hydrothermal vent site were
      determined. Lipid analyses and a comparative analysis performed with 16S rDNA
      sequences of similar thermophilic species showed that the strains isolated from
      deep-sea vents were not identical to the other species belonging to the genus
      Thermococcus. On the basis of the results of the phylogenetic analyses, lipid
      analyses, and previously reported physiological data, we believe that strains TY
      and TYS are significantly different from the previously described Thermococcus
      species. According to specific physiological and molecular features, we propose
      the use of these isolates as potential tools for the development of
      biotechnological applications in the field of starch processing and DNA
      technology.

PMID- 9148683
TI  - [What did the Medical Society of Warsaw contribute to Polish medicine].

PMID- 9148684
TI  - [Outstanding leaders of the Warsaw Medical Society].

PMID- 9148685
TI  - [History of the Warsaw Medical Society library].

PMID- 9148686
TI  - [About the versatility of Doctor Hiacynt August Dziardowski (1754-1828) in
      medical lectures].

PMID- 9148687
TI  - [Views of Henry Frederick Hoyer on the problem of causality. Record of
      philosophic history of medical thought in Poland].

PMID- 9148688
TI  - [Dr. Joseph Pawinski physician and humanist].

PMID- 9148689
TI  - [Historical outline of immune system study].

PMID- 9148690
TI  - [Medical demographics problems in the town of Cieszanow in the years 1801-1850].

PMID- 9148691
TI  - [Sanitation-hygienic state of Kamieniec Podolski in light of publications of the
      Podolski Medical Society in Kamieniec (1859-1865)].

PMID- 9148692
TI  - [Czar Peter and and balneology].

PMID- 9148693
TI  - [Colonel Dr. Medicine and Philosophy Antoni Stanislaw Wieckowski (1882-1942)].

PMID- 9148694
TI  - [Characterization of wool dust extract in vitro].
AB  - Wool dust has been described as a cause of respiratory impairment in workers
      occupationally exposed in wool processing. A pharmacological investigation was
      performed on 30 samples of isolated guinea plg trachea with wool dust water
      extracts prepared from the material collected at the workplace of exposed
      workers. Wool extract was added into the system with Krebs solution in
      progressively increased concentrations of 10, 30, 100, 300 and 1000 microliters.
      The constriction of the tracheal smooth muscle caused by wool dust extract was
      diminished after pretreatment with pyrilamine (antihistamine) and verapamil
      (intracellular and extracellular calcium blocking agent). Atropine
      (anticholinergic) and indomethacin (inhibitor of prostaglandin synthesis) had
      very little impact on the bronchoconstrictive effect of wool dust extract on the
      tracheal smooth muscle. This finding suggests that the airway constriction
      induced by wool dust is party attributable to mediators like histamine and also
      to calcium.

PMID- 9148695
TI  - [Mechanisms in the onset of nonspecific respiratory diseases caused by air
      pollutants in the work environment].
AB  - Mechanisms responsible for the development of occupational non-specific
      respiratory disease are presented. The roles of factors such as changes in airway
      smooth muscle, changes in airway mucosa and submucosa, altered regulation of the
      autonomous nervous system and the presence of an inflammatory process in the
      airways are described separately. Those changes may induce an increased
      reactivity of the bronchial system which is the main characteristic of
      obstructive lung disease.

PMID- 9148696
TI  - [Archives of Industrial Hygiene and Toxicology. 50 years since the founding of
      the journal].

PMID- 9148697
TI  - [Criteria for diagnosis of occupational asbestosis of the pulmonary parenchyma
      and pleura].

PMID- 9148698
TI  - Influence of electrically stimulated ankle plantar flexors on the swinging leg.
AB  - The influence of functional electrically stimulated ankle plantar flexors on the
      swinging lower extremity was studied in incomplete spinal cord injured persons.
      Stimulation sequences with different time and frequency parameters were delivered
      to ankle plantar flexors and knee extensors and to the peroneal nerve. The
      results of kinematic assessment showed that stimulated calf muscles provide
      noticeable forward and upward propulsion to the swinging leg.

PMID- 9148699
TI  - Lumbar root stimulation for restoring leg function: results in paraplegia.
AB  - We have implanted an intradural array of 12 tripolar electrodes on the anterior
      roots L2-S2, left and right, at cauda equina level, in a 33-year-old woman with a
      complete T9 cord lesion of 3 years' duration. They are driven by an implanted
      multiplexed stimulator system using radio frequency (RF) power and control
      signals. All channels generate movements, in patterns that might be predicted
      from the known anatomy of the cauda equina. In particular, stimulation of L2 and
      L3 gives hip adduction; L3, L4, and L5 gives quadriceps femoris movements; L5,
      S1, and S2 gives hamstrings movement; and S1 and S2 give plantar flexion.
      Stimulation of L5 gives mixed movements at the ankle. Surprisingly, stimulation
      of the L2 roots has not given strong hip flexion. Responses have been stable.
      Some thresholds have varied, probably as a result of tissue encapsulation. The
      moment generated within each degree of freedom of the legs has been measured for
      each root, using a specially designed multimoment measurement apparatus. For
      several roots, a movement of lower threshold may be accompanied by a second
      movement of higher electrical threshold, suggesting that different muscles may
      have fiber populations that differ in their diameter or their location in the
      root. The use of stimulus forms that enable selective anodal block may, in the
      future, enable separation of two distinct movements from a single motor root.

PMID- 9148700
TI  - Further development of hybrid functional electrical stimulation orthoses.
AB  - In this study two aspects of hybrid functional electrical stimulation (FES)
      orthoses were investigated: joint motion constraints and FES control strategies.
      First, the effects of joint motion constraints on the gait of normal subjects
      were investigated using modern motion analysis systems, including electromyogram
      (EMG) and heart rate measurements. An orthosis was developed to impose joint
      motion constraints; the knee and ankle could be fixed or free, and the hip joint
      could rotate independently or coupled, according to a preset flexion-extension
      coupling ratio (FECR). Compared with a 1:1 hip FECR, a 2:1 hip FECR was
      associated with a reduced energy cost and increased speed and step length. The
      knee flexion during swing significantly reduced energy cost and increased walking
      speed. Ankle plantar flexion reduced the knee flexing moment during the early
      stance phase. Second, trials on 3 paraplegic subjects were conducted to implement
      some of these findings. It appeared that the 2:1 FECR encouraged hip flexion and
      made leg swing easier. A simple FES strategy increased walking speed and step
      length and reduced crutch force impulse using fixed orthotic joints.

PMID- 9148701
TI  - Hypertrophy and transformation of muscle fibers in paraplegic patients.
AB  - Transcutaneous electrical stimulation of the quadriceps femoris muscle was
      applied in 14 paraplegic patients (10 spastic patients with spinal cord lesions
      and 4 patients with conus-cauda lesions with denervation atrophy). In both the
      spastic and the denervated group, the vastus lateralis muscle was biopsied and
      computed tomography (CT) images of the entire upper leg were made both at the
      onset and termination of the 8-month training period. The stimulation was carried
      out twice a day for 20 min. The increase in muscle tissue was significant in the
      CT images. The biopsies showed that the fiber diameter of both fiber types
      increased during the training period in the spastic group from 47 to 67 microns
      and in the denervated group from 22 to 38 microns. In both groups, the
      differences were significant between the first and second biopsies. Both groups
      showed a marked Type 2 fiber predominance. The histological and CT findings
      correlated with the clinical improvement of muscle function.

PMID- 9148702
TI  - Stability and energy criteria in healthy and paraplegic subject gait.
AB  - The functional electrical stimulation (FES) assisted gait of paraplegic patients
      is inferior to that of healthy subjects. The difference can be observed in terms
      of speed, upright balance, biomechanical energy consumption, and generation of
      propulsion forces in the direction of walking. The biomechanical structure of
      paraplegic subjects is the same as that of normal ones; however, the mode of
      walking differs significantly because of the reduced number of activated muscles
      and primitive control. The healthy subject is utilizing a 2-point dynamically
      stable gait. The paraplegic patient is using 4-channel FES and utilizing a 4
      point statically stable gait. We believe that the FES gait can be improved if
      converted into a semidynamically or dynamically stable gait. The gait is
      considered statically stable if the center of gravity (COG) projection on the
      ground (PCOG) is inside the supporting area. For a quadruped, this is only
      possible if it is utilizing a creeping crawl gait. In this paper, the
      relationship between PCOG and the supporting area are discussed as a criterion
      for dynamic stability assessment. Results are shown for 3 different modes of 2
      point and 4-point gaits.

PMID- 9148703
TI  - Functional electrical stimulation in paraplegic spastic patients.
AB  - We are reporting on the clinical and physiological effects of 8 months of
      functional electrical stimulation (FES) of the quadriceps femoris muscle on 10
      paraplegic patients. Each patient had muscle biopsies, computed tomography (CT)
      muscle diameter measurements, and knee extension strength testing both before and
      after 8 months of FES training. Skin perfusion was documented through infrared
      telethermography and xenon clearance; muscle perfusion was recorded through
      thallium scintigraphy. After 8 months of FES training, the baseline skin
      perfusion showed an 86% increase; muscle perfusion was augmented by 87%. Muscle
      fiber diameters showed an average increase of 59% after 8 months of FES training.
      Muscles in patients with spastic paresis showed an increase in aerobic and
      anaerobic muscle enzymes up to the normal range of healthy humans. The increment
      in muscle area, as visible on CT scans of the quadriceps femoris muscle, was 30%.
      Using FES, we were able to improve metabolism and to induce positive trophic
      changes in our patients' lower extremities. In spastic paraplegics, rising and
      walking achieved through FES are much better training than FES ergometer
      training. Larger muscle masses are activated, and the heart rate is increased;
      therefore, the impact on cardiovascular fitness and metabolism is much greater.
      This effectively addresses and prevents the problems that result from inactivity
      in paraplegic patients.

PMID- 9148704
TI  - Wireless control of functional electrical stimulation systems.
AB  - With the assistance of crutches and functional electrical stimulation (FES), we
      are able to restore standing and simple gait in some spinal cord injured (SCI)
      patients. In present rehabilitative systems, the patient divides the gait cycle
      into stance and swing phases via pushbuttons mounted on the handles of the
      crutches, which are hardwired to the functional electrical stimulator. The
      surface-mount technology based telemetry system, which makes use of the
      radiofrequency medium at 40 MHz, was developed to provide wireless control of the
      FES system. Signals from crutch pushbuttons were coded and transferred from the
      transmitter to the receiver. The receiver was firmly attached to the patient's
      waist and was connected to the stimulator.

PMID- 9148705
TI  - Improvement of microcirculatory blood flow under epidural spinal cord stimulation
      in patients with nonreconstructible peripheral arterial occlusive disease.
AB  - Epidural spinal cord stimulation (ESCS) has been suggested as a method to improve
      microcirculatory blood flow and to reduce the amputation rate in vascular
      patients. We studied the effects of ESCS on microcirculatory blood flow in 237
      patients with nonreconstructible peripheral arterial occlusive disease. Clinical
      status was classified as Fontaine Stage 3 (ischemic rest pain) in 169 patients
      and as Fontaine Stage 4 (ulcers/gangrene) in 68 patients. After a mean follow-up
      period of 31.2 months, major pain relief (> 75%) was noticed in patients who
      retained their limbs. Sixty-four patients underwent major amputation despite
      ESCS. Clinical improvement was confirmed by the increase in transcutaneous oxygen
      (TcPO2).

PMID- 9148706
TI  - Effect of long-term implanted nerve cuff electrodes on the electrophysiological
      properties of human sensory nerves.
AB  - During a long-term implantation (307 days) of a tripolar split cuff electrode
      around the palmar digital nerve to the radial side of the left index finger,
      branching off the median nerve in a medullary lesioned C6 patient, the
      physiological state of the nerve was intensively monitored. The resulting sensory
      nerve action potential (SNAP) amplitude was recorded, using both near-nerve
      electrodes and the implanted cuff electrode. The SNAP amplitude declined within
      10 days to approximately 50% of the first SNAP cuff amplitude measured on Day 2
      after implantation and recovered to the initial amplitude within 3 months. The
      SNAP amplitude measurements made with near-nerve electrodes were consistent with
      the cuff results; the SNAP conduction velocity (CV) recorded by the near-nerve
      electrodes and the cuff electrode was constant during the whole implantation
      period. This is in agreement with the results from two other patients: one with a
      cuff implanted around the sural nerve, and the other with a cuff implanted around
      a branch of the tibial nerve. These results and animals studies show that the
      cuff electrode is an electrically stable neural-electrical transducer.

PMID- 9148708
TI  - Simulation of the electrically stimulated auditory nerve.
AB  - The electrically generated firing pattern in the fibers of the primary auditory
      nerve is simulated for a monopolar stimulating electrode. Using an analogous
      input speech signal, the spiking pattern produced with a single electrode has a
      simple structure, which unfortunately makes no use of the 2 important coding
      principles used by nature. By computer simulation, it is possible to obtain an
      approximation of the firing pattern of the auditory nerve fibers. Listening to
      the information carried by the compound action potential of the auditory nerve
      demonstrates that speech signals with dominant high-frequency components are
      difficult or not possible to discern. This paper presents a strategy for speech
      processing that seems to improve speech understanding for single-channel implant
      patients because neural patterns consisting of more temporal information can be
      generated.

PMID- 9148707
TI  - Useful applications and limits of battery powered implants in functional
      electrical stimulations.
AB  - Battery powered stimulation implants have been well-known for a long time as
      heart pacemakers. In the last few years, fully implantable stimulators have been
      used in the field of functional electrical stimulation (FES) for applications
      like dynamic cardiomyoplasty and electro-stimulated graciloplasty for fecal
      incontinence. The error rate of battery powered implants is significantly smaller
      than that for conventional stimulator systems, and the quality of life for the
      patients is increased because the need for an external power and control unit is
      eliminated. The use of battery powered implants is limited by the complexity of
      the stimulation control strategies and the battery capacity. Therefore,
      applications like the stimulation of lower extremities for walking, cochlea
      stimulation, or direct muscle stimulation cannot be supported. The improvement of
      implantable batteries, microcontrollers, and ultralow power products is ongoing.
      In the future, battery powered implants will also meet the requirements of
      complex applications. Systems for restoration of hand and breathing functions
      after spinal cord injury can be the next field of use for battery powered
      implants. For these purposes, we developed a battery powered multichannel implant
      with a sufficient life span for phrenic pacing. The problems during development
      and the limits of this system are described in this paper.

PMID- 9148709
TI  - Computer aided adjustment of the phrenic pacemaker: automatic functions,
      documentation, and quality control.
AB  - Electrical stimulation of the phrenic nerves of patients with complete
      ventilatory insufficiency with the Vienna respiratory pacemaker has been in
      clinical use since 1983. During the adjustment of stimulation parameters with
      this device, the following problems have occurred: for some measurements like the
      recruitment curve, series of complete inspiration cycles have to be stimulated,
      which causes the danger of muscle fatigue for unconditioned patients. The
      documentation is completed predominantly by hand, taking time and increasing the
      possibility of error. As a first step to solve these problems, we developed a new
      stimulation and measurement system. It consists of a PC with data acquisition
      hardware, the necessary sensors, and amplifier circuitry. The implanted
      stimulator is controlled via the parallel interface. The new system offers some
      advantages: computer control shortens the time for measurement and documentation,
      and the stress on the patient and the risk of error is reduced; synchronized
      measurement makes it possible to use single stimulation pulses instead of bursts
      and ramps to reduce diaphragm fatigue; digital signal processing improves
      measurement results and reproducibility; and help functions and self tests are
      provided, together with a graphical user interface. We used sensors for air flow,
      diaphragm EMG, and acceleration, on up to 8 channels simultaneously. Combined
      sample rates of up to 100 kS/s were possible. The system could be adapted for
      other uses involving functional electrical stimulation with our implantable nerve
      stimulators. Using this equipment saves a lot of effort, and the adjustment
      process can be focused on improved stimulation results and better performance for
      the patient. Current research is studying implementation of automatic functions
      like acquisition of stimulation thresholds. This could result in a predominantly
      automated adjustment of the phrenic pacemaker and even in a closed-loop
      controlled system in the future.

PMID- 9148710
TI  - Implantable volume monitor and miniaturized stimulator dedicated to bladder
      control.
AB  - This paper describes a new miniaturized implantable bladder controller that is
      composed of 4 main parts: a volume monitoring device based on the tomography
      approach, a fully programmable miniaturized central processor and stimulator, a
      bidirectional data and power link, and an external controller. The proposed
      system is intended to restore both normal bladder functions (retention and
      voiding) to spinal cord injured patients. The system contains a mixed-signal
      (analog/digital) feedback loop to command the bladder functions through
      neuromuscular stimulation techniques. The implantable circuitry is powered by a
      single encoded radiofrequency carried and may have up to 8 independently
      controlled monopolar (4 bipolar) channels. The microstimulator is able to
      generate a wide range of stimulation patterns, including selective stimulation
      waveforms. In addition, an optical link transmits the state of the implant and
      volume monitoring results to the external controller.

PMID- 9148711
TI  - Selective detrusor activation by electrical stimulation of the human sacral nerve
      roots.
AB  - The purpose of this study was to investigate the feasibility of selective
      detrusor activation without activation of the urethral sphincter by sacral root
      stimulation in patients. The sacral roots were stimulated using a tripolar
      electrode. An anodal block was used to prevent the urethral sphincter from
      contraction. Using square current pulses (700 microseconds, 6-7 mA), no increase
      in intraurethral pressure was measured, while a normal increase in intravesical
      pressure occurred. The minimum pulse duration to obtain a complete block was 550
      microseconds. The study shows that anodal blocking of action potentials is
      possible in humans and can result in selective detrusor activation when used in
      sacral root stimulation.

PMID- 9148712
TI  - Natural versus artificial sensors applied in peroneal nerve stimulation.
AB  - We have attempted to quantify the performance of natural versus artificial
      sensors when used in a closed-loop functional electrical stimulation system.
      Peroneal nerve stimulation was applied during gait to a multiple sclerosis
      subject with a drop foot. Stimulation was applied only during the swing phase to
      provide artificially induced dorsiflexion of the foot. Detection of the onset of
      the stance phase was accomplished using a standard heel contact switch mounted
      inside the subject's shoe (the artificial sensor) and using processed nerve
      signals derived from an implanted nerve-cuff electrode (the natural sensor). A
      detection percentage of at least 85% was achieved using the afferent nerve signal
      information only. When muscle activity (also recorded in the cuff) and additional
      information about the gait cycle were incorporated, functional detection ratios
      approaching 100% were achieved.

PMID- 9148714
TI  - Predicted and measured muscle forces after recoveries of differing durations
      following fatigue in functional electrical stimulation.
AB  - Using 31P nuclear magnetic resonance (NMR) spectroscopy, the bioenergetics of
      paralyzed muscles activated by functional electrical stimulation (FES) were
      studied in vivo during fatigue and recovery on paraplegic subjects. During the
      activation phase of the muscle, the muscle force was also monitored. The
      phosphorus metabolites were found to vary systemically during the fatigue and to
      recover slowly to their rest state values after cessation of FES. During fatigue,
      a good correlation was found between the decaying force and each of the profiles
      of phosphocreatine, inorganic phosphorus, and intracellular pH. A musculotendon 5
      element model was proposed for the activated muscle to predict its force
      generation capacity. A fatigue recovery function, based on the metabolic
      profiles, was introduced into the model. This model allowed us to predict the
      force expected to be developed as a function of the time after recovery of given
      time durations. Validation experimental measurements of force were carried out
      and included recurrent fatigue tests, both in the initially unfatigued state and
      at various times in the postfatigue stage of the muscle. Comparison of the
      predicted and measured forces indicated satisfactory agreement of the results.
      The developed model of muscle dynamics should help to design a strategy for
      reducing muscle fatigue under FES.

PMID- 9148713
TI  - Comparison of simulation and experiments of different closed-loop strategies for
      functional electrical stimulation: experiments in paraplegics.
AB  - Open-loop and closed-loop stimulation of the knee extensors for the control of
      the knee joint angle and torque were tested as a potential basis for more complex
      functional electrical stimulation (FES) systems to be used in human locomotion.
      The output of the biomechanical simulation model described previously was
      compared with stimulation experiments in patients with complete thoracic spinal
      cord injury. Good correspondence between simulation and experiments was obtained
      under both isometric conditions and conditions with a freely swinging shank. For
      closed-loop control, a simple proportional integral derivative (PID) controller
      yielded sufficient performance only under isometric conditions, especially if
      combined with (linear) feedforward. Because of additional nonlinearities of
      musculotendon and body segmental dynamics, more complex strategies have to be
      applied to the control of unconstrained movements. To compensate for these
      nonlinearities, an inverse model was derived from the direct biomechanical model.
      This inverse model had satisfactory agreement between the measured knee angle and
      the desired trajectory already under open-loop conditions. A combination of the
      inverse model in the feedforward part of the control loop and a PID controller
      provided robust and precise control of the knee angle. Further improvement may be
      achieved by including elements of spasticity into the simulation model and by
      controlling both agonistic and antagonistic muscles.

PMID- 9148715
TI  - Measuring of skeletal muscles' dynamic properties.
AB  - Many studies have been completed to determine how muscles work. One of the
      aspects to study is the muscle response and how to measure it. The main aim of
      this study was to build a noninvasive measuring system that would be simple to
      use and would measure the muscle response as close to the muscle as possible. The
      measuring method was based on a magnetic displacement sensor measuring the muscle
      belly response. The sensor was placed adjacent to the skin over the muscle and
      measured radial movements of the muscle belly. The muscle response to single
      twitch electrical stimulation was measured. Different skeletal muscles or muscle
      groups have different biomechanical characteristics. The rise time of the muscle
      belly response was the characteristic parameter for this study. The comparison of
      muscles' responses in terms of the values of their normalized rise time
      parameters confirmed their identities as slow or fast muscles. The value of the
      normalized rise time parameter of a slow muscle was four times less than the
      value of the parameter of a fast muscle. Although the question remains as to how
      the available measuring techniques provide estimation of skeletal muscles'
      dynamic properties, this proposed measuring method contributes to a better
      understanding of skeletal muscles' dynamic properties. It offers a possible way
      of studying the muscle structure from the muscle's response to electrical
      stimulation in a simple noninvasive way.

PMID- 9148716
TI  - Effect of adaptive pulse train duration on latissimus dorsi blood flow.
AB  - Blood flow, intramuscular pressure, and stroke work of the trained latissimus
      dorsi muscle (LD) were measured during electrical stimulation at contraction
      rates between 20 and 160/min using pulse trains of 2 to 6 pulses in length.
      Epimysial electrodes and intramuscular pressure sensors were implanted in the LD
      of 5 dogs. The muscle remained in situ. After 12 weeks of a progressive training
      protocol, LD blood flow (BF) was measured using an ultrasonic flow probe and work
      (SW) was determined from the measured force and shortening. For pulse trains of 2
      or 3 pulses, BF increased with rate, and SW was maintained at all rates. For 4
      pulses, BF and SW decreased when the contraction rate exceeded 120/min. SW
      decreased above 100/min and 80/min for 5 and 6 pulses, respectively. An upper
      rate limit dependent upon the pulse train duration exists above which BF and SW
      decline. Exceeding these upper rate limits should be avoided in cardiomyoplasty.
      Excessive stimulation rates could be detrimental to the muscle by creating a
      metabolic insufficiency or ischemia. The cardiac assistance benefit is
      compromised as SW declines during high contraction rates of long pulse train
      duration.

PMID- 9148717
TI  - Lumbar root stimulation for restoring leg function: stimulator and measurement of
      muscle actions.
AB  - We are studying the feasibility of restoring lower limb functions to paraplegics
      by stimulating their lumbar anterior roots (L2-S2). The potential advantages of
      placing electrodes at the roots, at the cauda equina, were set out by Rushton
      (1), and our results so far are in a companion paper by Rushton et al. In this
      paper, we describe briefly the stimulator system and a special apparatus we call
      the multimoment chair. The stimulator is a development from an earlier design of
      an implantable peripheral nerve stimulator (2) and has features that make it
      easier to use. The multimoment chair enables us to gather simultaneously
      isometric joint moments for 14 axes of the legs during stimulation while the body
      is fixed in a posture between sitting and full extension. Such rapid data
      collection is essential to discover the effects of multiple-root stimulation and
      its functional possibilities.

PMID- 9148718
TI  - Restoration of lateral hand grasp using natural sensors.
AB  - A closed-loop control system for controlling the key grip of a C6 tetraplegic
      patient was developed. Natural sensors served as the source of the feedback
      signal. The neural signals from cutaneous receptors were picked up by an
      implanted cuff electrode placed around the radial branch of the median nerve
      innervating the lateral part of the index finger. Mechanical stress applied to
      the skin, like pressure and slips, resulted in an increase in amplitude of the
      recorded neural signal. The goal of the study was to determine whether the
      recorded neural signals were able to indicate the slip of an object during
      lateral grasp and whether the slip could be stopped by increasing the grasp force
      through functional electrical stimulation of the thumb adductor and flexor.

PMID- 9148719
TI  - Experience of clinical use of the Odstock dropped foot stimulator.
AB  - The Odstock dropped foot stimulator (ODFS) is a simple functional electrical
      stimulation (FES) device for the correction of dropped foot. Improved
      reliability, fine control of stimulation parameters, and careful application and
      follow-up have let to 86% compliance. Data on 56 patients (50 patients with
      hemiplegia, 5 patients with multiple sclerosis, and 1 patient with spinal cord
      injury) who have used the system for between 6 and 18 months are presented and
      show a statistically significant increase in walking speed with the stimulator at
      3 months of 14% (p < 0.001); decreased effort of walking, measured as
      physiological cost index (PCI), of 37% (p < 0.001); and statistically significant
      improvement in functional mobility tests and questionnaires. No statistically
      significant carryover was seen although 3 patients had sufficient improvement in
      active ankle control and gait parameters to no longer need the stimulator. Six
      patients who used the stimulator all day every day had a problem with skin
      irritation, which we have not yet been able to solve. Two patients discontinued
      use after experiencing increased spasticity in the calf.

PMID- 9148720
TI  - Nerve fibre interaction with large ganglion cells in the human spiral ganglion. A
      TEM study.
AB  - A TEM study was performed on freshly fixed human spiral ganglions (HSG) biopsied
      during skull base surgery. Well preserved tissue specimens were obtained for
      ultrastructural analysis. The investigation revealed that nerve fibres frequently
      form contacts with the large ganglion cells (type I cells). In the areas of
      contact, membrane specializations occurred, consisting of symmetric or asymmetric
      densities often alternating from one cell to the other with a reduced
      intercellular distance (approximately 10 nm). High power TEM showed the
      intercellular cleft to contain an extra dense line resulting in a pentalaminar
      structure. The dense line appeared on the side of the membrane protein
      concentration. Protein densities jutted into the cytoplasm along the
      intracellular face spreading into a diffuse cytoplasmic web physically related to
      accumulating mitochondria. This indicated a concentration of oxygen-dependent
      metabolic activity in these regions. It is believed that the nerve junctions are
      involved in electric transmission between type I ganglion cells. The neural
      junctions were morphologically different from synaptic contacts between small
      human ganglion cells (type II cells) and nerve fibres which have been suspected
      of sharing the olivocochlear bundle as their origin.

PMID- 9148721
TI  - Accessory parotid gland tumor: a case report.
AB  - We report a case of pleomorphic adenoma which was assessed pre-operatively as
      arising from the accessory parotid gland. Computed tomography (CT)-sialography
      provided information about the relationship between the tumor and the remaining
      normal accessory parotid tissue, and fine-needle aspiration of the tumor provided
      additional information as to the histologic features of the tumor, i.e. it was
      identified as of salivary origin. Zygomatic and buccal branches of the facial
      nerve extended over the accessory parotid gland tumor and the parotid duct was
      located just beneath the tumor. Therefore, pre-operative assessment of the
      tumor's nature was important for prevention of facial nerve damage and salivary
      fistula. The normal accessory parotid gland tissue associated with the accessory
      parotid tumor was histologically different from that of normal parotid gland
      tissue dissected in other patients with pleomorphic adenoma of the parotid gland.
      It is suggested that the difference in cell composition between these glands
      affects the development of the associated tumors.

PMID- 9148722
TI  - Endoscopic surgery of uni- and bilateral choanal atresia.
AB  - From 1992 to 1996 six children and one adult woman presented at our clinic with
      choanal atresia. In four newborns bilateral choanal atresia was found and in two
      older infants and one adult unilateral atresia was discovered. Although several
      different techniques for management of posterior choanal atresia (PCA) are
      described already in the literature, we decided to try a new approach using rigid
      endoscopes. This techniques enables the surgeon to visualize the whole atresia
      plate directly and to see the tips of his instruments. Under direct view it is
      possible to safely remove the bony plate and to allow immediately for an adequate
      and persistent airway. This technique is less traumatic and minimizes the risks
      of conventional surgery. Follow-ups after 1, 2 and 3 years still showed remaining
      opening of the posterior nose and normal physical development. A second surgical
      intervention was necessary after 9 months in one case of a newborn however, in
      whom the first procedure was performed as an emergency on the second day of his
      life.

PMID- 9148723
TI  - Translabyrinthine vestibular schwannoma surgery: postoperative tinnitus and
      cochlear nerve integrity.
AB  - Cochlear neurectomy as a surgical treatment for tinnitus is known to be only
      partially successful in many conditions. Translabyrinthine surgery for acoustic
      neuromas may be performed using a dissection technique which preserves an
      'anterior curtain' which helps to protect the facial nerve. The cochlear nerve
      may be retained within this tissue though it can be cut during the dissection. To
      assess whether its integrity affects tinnitus the video recordings of 117
      patients undergoing this operation were reviewed to grade the likelihood of the
      cochlear nerve having been retained intact. A postal questionnaire, with a
      response rate of 83%, was used to assess tinnitus. Patients who had a probable or
      definite nerve section had significantly lower postoperative tinnitus severity.
      The same relationship was found when patients were matched for tumour size and
      preoperative tinnitus. This procedure could act as a model for the effect of
      cochlear neurectomy on tinnitus associated with acoustic neuromas in a
      prospective trial.

PMID- 9148724
TI  - Ultrastructural analysis of the vestibular nerve in Meniere's disease.
AB  - Numerical analysis of the vestibular nerve in Menie's disease was performed.
      Vestibular nerve specimens were obtained from three patients with classical
      clinical findings of Meniere's disease during retrosigmoid vestibular neurectomy.
      For each patient, an ultrathin section, including an entire cross-section of the
      nerve specimen, was examined. Fiber counts of nerve specimens with definite
      pathologic findings were compared with caloric testing results. A significant
      correlation was found between reduced vestibular response and the incidence of
      abnormal nerve fibers and also the density of the abnormal nerve fibers. However,
      the number of nerve fibers with pathologic findings was small. Results of the
      present study demonstrate no general degeneration of nerve fibers caused by the
      disease process of Meniere's disease.

PMID- 9148725
TI  - Developmental morphology of the middle ear.
AB  - The development of the murine middle ear was monitored both qualitatively and
      morphometrically by scanning electron microscopy from the 19th gestational day to
      the adult stage. At birth, the middle ear was less well developed than the inner
      ear. The tympanic membrane (TM) was obscured by occlusion of the external
      auditory canal. Ciliated cells and secretory granules were present in the middle
      ear epithelium already 5 days after birth (DAB). Keratin debris was discerned on
      the external layer of the TM 9 DAB. By 12 DAB, mesenchymal tissue had resorbed
      from the middle ear cavity, except around the upper part of the ossicles. The
      middle ear was immature at birth but developed rapidly until 12 DAB. When
      compared with the avian middle ear the mouse middle ear was basically similar to
      that of humans, although in the human the stapedial artery is vestigial whereas
      in the mouse it persists as an important vessel. In man, there is no orbicular
      apophysis and no gonial of the malleus. The hypotympanum of the human middle ear
      is less developed than that of the murine middle ear. The mouse external auditory
      canal matures postnatally until 12 DAB, while in humans its development is
      complete at birth.

PMID- 9148726
TI  - Efficacy of transmeatal low power laser irradiation on tinnitus: a preliminary
      report.
AB  - Thirty-eight patients suffering from tinnitus resistant to several medical
      therapies for more than 6 months were treated by low power laser irradiation. A
      40 mW laser with a wavelength of 830 nm was irradiated via their external
      auditory meatus toward the cochlea for 9 min once a week, 10 times or more.
      Patients were asked to score their symptoms on a 5 point scale before and after
      the treatment for a subjective evaluation of the effect. The results were
      estimated by the change of the loudness and duration of tinnitus, and the degree
      of annoyance due to tinnitus. Although only 26% of the patients had improved
      duration, loudness and degree of annoyance were relieved in up to 58 and 55%,
      respectively, without major complication. Laser therapy seemed to be worth trying
      on patients with intractable tinnitus.

PMID- 9148727
TI  - Simple in-office closure of small intractable tympanic membrane perforations
      after myringoplasty.
AB  - Perforations produced following myringoplasty are very difficult to close by
      ordinary cautery or patching even if they are small. Therefore we decided to
      close these intractable perforations with a skin graft from the cartilaginous ear
      canal. Our method is an in-office operation under local anesthesia. After the
      removal of epithelium from around the perforation a skin graft was placed by the
      over-lay method. A total of 11 patients were treated, of which 81.8% (9/11)
      demonstrated successful closure in the initial surgery and two re-perforations
      were successfully closed by a second and third operation, respectively. The
      technique used in this surgery is relatively easy and appropriate for in-office
      operations. The method's advantages include decreased invasiveness with minimal
      anesthesia and no requirement for ear canal packing or fixatives, and cosmetic
      benefit. This method also can be applied to perforations caused by chronic otitis
      media, traumatic perforations, and perforations after inserting tubes.

PMID- 9148728
TI  - Evaluation of mastoid air cell system by three-dimensional reconstruction using
      sagittal tomography of the temporal bone.
AB  - The mastoid air cell system has been recognized as an important contributor to
      the pathophysiology of middle ear inflammatory diseases. Various methods of
      temporal bone imaging have been designed to investigate the correlation between
      middle ear disease and mastoid pneumatization. In this study, the mastoid air
      cell system was reconstructed three-dimensionally from sagittal tomographic
      images of the temporal bone on X-ray films, using a personal computer to evaluate
      the mastoid pneumatization in a total of 29 patients with chronic otitis media,
      adhesive otitis media, adhesive-type cholesteatoma, attic cholesteatoma and
      cholesterol granuloma, and in five normal subjects as controls. Reconstructed
      three-dimensional images of the mastoid air cell system and its volume were
      analyzed. The reconstructed images were helpful in recognizing the three
      dimensional solid appearance of the mastoid air cell system. The volume of the
      reconstructed mastoid air cell system was significantly reduced compared with
      that in the controls in each of the patient groups. Mastoid pneumatization in the
      patients with adhesive-type cholesteatoma was significantly suppressed compared
      with that in the adhesive otitis media patients. Interestingly, the adhesive
      otitis media group showed cell development at the tip of mastoid process, whereas
      the group of adhesive-type cholesteatoma did not, suggesting a difference in the
      pathophysiology in the two diseases. We found that three-dimensional
      reconstruction of the temporal bone using sagittal tomographic images was useful
      in evaluating the state of mastoid air cell system development in individual
      cases and in investigating the pathophysiology in middle ear disease.

PMID- 9148729
TI  - The relationship between orthostatic dizziness and hypotension in male medical
      students.
AB  - We carried out a questionnaire survey regarding symptoms of orthostatic
      dysregulation (OD) and administered the Schellong test (orthostatic test) to 123
      normal male medical students aged 21-29 years to investigate the relationship
      between orthostatic dizziness and hypotension. OD was identified in 15 (12.2%) of
      the subjects based on the questionnaire results. Orthostatic dizziness was noted
      in 40.7% of the subjects (50/123). The occurrence of orthostatic dizziness was
      most significantly related to systolic pressure decrease during the procedure for
      the Schellong test. These results suggest that the testing procedure introduced
      by Schellong can be useful, and clinically applicable to the assessment of
      orthostatic dizziness, since it presents the advantage of being simple enough to
      carry out in clinical practice.

PMID- 9148730
TI  - Distribution of vasoactive intestinal polypeptide immunoreactive nerve fiber in
      the rat nasal mucosa.
AB  - The distribution of vasoactive intestinal polypeptide (VIP)-immunoreactive nerve
      fiber of the respiratory nasal mucosa of the rat was examined by use of
      immunohistochemistory with light, laser confocal scanning and electron
      microscopy. On light microscopy, it was observed that VIP immunoreactive nerve
      fibers distributed under and within the epithelium in addition to around the
      blood vessels and glands. The laser confocal scanning microscope revealed the
      network of VIP-immunoreactive nerve fibers at glands, but it was denser around
      glands than within glands. The VIP-immunoreactive nerve fibers formed fine
      varicosities and was distributed below the middle portion of the epithelium. Some
      fibers were observed as if they were surrounding goblet cells. Electron
      microscopy showed that the VIP-immunoreactive nerve fibers within the epithelium
      were terminated as free nerve endings. Some of them were in close contact with
      goblet cells.

PMID- 9148731
TI  - Neovascularization of the intestinal graft transplanted in subcutaneous pocket in
      rats.
AB  - Clinically, the intestinal graft can survive without blood supply through its
      vascular pedicle for a certain period after transplantation, which is generally
      considered to be due to newly formed vessels from the surrounding tissue to the
      graft. Vascular synthesis from the surrounding tissue to the pedicled intestinal
      graft, transplanted subcutaneously was studied in rat model. Both the carbon dye
      infusion technique and hematoxylin-eosin stain were employed. After
      transplantation of the intestine, the number and diameter of carbon stained
      vessels were scored on days 2, 5, 7, 10, 14, 28, and 56, when the pedicle was
      ligated. All the histological specimens of the intestinal grafts were analyzed
      and then classified into three phases depending on the extent of surviving
      mucosa: 'necrosis', no live mucosa were observed; 'incomplete take', some islands
      of mucosa were alive; and 'complete take', all mucosa were alive. We
      characterized the relationship between the changes of the newly formed (carbon
      dyed) vessels and the three histological phases. At 'necrosis', the newly formed
      vessels were rare and did not reach the intestinal graft. At 'incomplete take',
      random thin vascular networks were observed and some of them reached the graft.
      Some specimens were in the 'incomplete take' phase. At 'complete take', regular
      large vascular networks were observed. This transformation of the vascular
      networks seemed to reduce the the resistance of the vascular flow and to finally
      lead to the 'complete take' of the graft.

PMID- 9148732
TI  - Characteristics of laryngeal receptors analyzed by presynaptic recording from the
      cat medulla oblongata.
AB  - In order to clarify the neural mechanisms for the protective laryngeal reflex, we
      conducted physiological analysis of laryngeal sensory receptors. In the present
      study, presynaptic unit activities, which might accurately reflect
      characteristics of the laryngeal receptor, were recorded with a glass
      microelectrode in the nucleus of the tractus solitarius of the medulla oblongata
      in ketamine-urethane anesthetized cats, and the responses to the mechanical
      and/or chemical stimuli were analyzed. From the results, it was demonstrated that
      highly sensitive mechanoreceptors and polymodal receptors exist in the laryngeal
      mucosa; they are particularly numerous in the laryngeal surface of the epiglottis
      and arytenoid region, and uncommon in the vocal fold. Mechanoreceptors on the
      laryngeal mucosa were classified into a rapidly adapting group and a slowly
      adapting group, while all polymodal receptors adapted rapidly to mechanical
      stimulation. These results suggest that these non-specific polymodal and rapidly
      adapting receptors may correspond to more superficial receptors such as free
      nerve endings and some taste buds, and also monomodal slowly adapting
      mechanoreceptors may correspond to deeper terminals in the subepithelium. It is
      also considered possible that the structures and the characteristics of these
      receptors are appropriate to elicit the protective laryngeal reflexes by non
      specifically detecting various kinds of stimuli.

PMID- 9148733
TI  - Prognostic value of nucleolar organizer regions in supraglottic carcinoma.
AB  - The relationship of nucleolar organizer regions (NORs) to proliferative activity
      and tumor progression was studied in 16 supraglottic carcinomas. The number of
      NORs stained by a silver colloid staining method (AgNOR staining method) was
      determined. The mean AgNOR number tended to be higher (but not significantly so)
      in poorly differentiated tumors. Moreover as T and N categories and stage of the
      tumor rose, the AgNOR number also rose, but not significantly. More
      interestingly, the mean AgNOR number was significantly higher in the presence
      than in the absence of lymph node metastasis. These studies indicate that the
      AgNOR number might be of clinical value as a predictor of lymph node metastasis
      of supraglottic carcinomas.

PMID- 9148734
TI  - Surgical rehabilitation of deafness with partially implantable hearing aid using
      piezoelectric ceramic bimorpli ossicular vibrator.
AB  - We developed two types of implantable hearing aids, a totally implantable hearing
      aid (TIHA) and a partially implantable hearing aid (PIHA) in 1983. In both types
      a piezoelectric ceramic bimorph was used as an ossicular vibrator which was
      coupled to the stapes to transmit sound signals to the inner ear efficiently. Due
      to technological immaturities, clinical application of the TIHA has not yet been
      realized. But the PIHA is available for clinical use at present. In the PIHA only
      the ossicular vibrator is implanted with inner link coil. The rest of components
      such as microphone, amplifier, battery, and outer link coil remain in their usual
      location behind the auricle. Since 1984, we have applied the PIHA to 37 patients
      with mixed deafness. Careful follow-up studies have been conducted on all of them
      to assess clinical and audiological results. We have confirmed that the device
      could function safely for more than 10 years affording natural quality of hearing
      without howling and wearing discomforts. Our studies suggest that the PIHA can be
      a choice of rehabilitation for mixed deafness due to middle ear diseases which
      cannot be rehabilitated satisfactorily by either surgical means or a conventional
      hearing aid. Functional principle of device, indications and surgical methods of
      implantation were described. Failures and delayed problems we experienced were
      also presented together with the preventive measures. We believe that an
      implantable hearing aid of this type will be an otologic breakthrough if
      substantial technological difficulties are cleared.

PMID- 9148735
TI  - Unilateral acoustic neuroma in childhood.
AB  - Three cases of unilateral acoustic neuroma in childhood that are associated with
      neither neurofibromatosis type 1 nor type 2 were reported. All three cases had a
      hearing disorder as an initial symptom. Two of them had a large neuroma and had
      considerable abnormal findings in neurootological examinations, and one case with
      an intracanalicular tumor showed a unilateral progressive sensorineural hearing
      loss that had no response to steroid administration. Surgical removal of the
      tumor was carried out for these cases. Different approaches were used in each
      case; suboccipital approach, one-stage suboccipital and middle fossa approach,
      and middle fossa approach. Although the facial nerve functions were fairly well
      maintained, hearing preservation could not be attained in all. Papers dealing
      with this tumor were reviewed, and certain characteristics of cases with acoustic
      neuroma in childhood were discussed.

PMID- 9148736
TI  - You're the flight surgeon: sickle cell trait and beta-thalassemia.

PMID- 9148738
TI  - Rapid decrease in cellular sodium and chloride content during cold incubation of
      cultured liver endothelial cells and hepatocytes.
AB  - Hypothermia, as used for organ preservation in transplantation medicine, is
      generally supposed to lead to an intracellular accumulation of sodium, and
      subsequently of chloride, via inhibition of the Na+/K+-ATPase. However, on
      studying the cellular sodium concentration of cultured liver endothelial cells
      using fluorescence microscopy, we found a 55% decrease in the cellular sodium
      concentration after 30 min of cold incubation in University of Wisconsin (UW)
      solution. To confirm this surprising result, we set up a capillary
      electrophoresis method that allowed us to determine the cellular contents of
      inorganic cations and of inorganic anions. Using this method we measured a
      decrease in the cellular sodium content from 104+/-11 to 55+/-4 nmol/mg of
      protein, accompanied by a decrease in the chloride content from 71+/-9 to 25+/-5
      nmol/mg of protein, after 30 min of cold incubation in UW solution. When the
      endothelial cells were incubated in cold Krebs-Henseleit buffer or in cold cell
      culture medium instead of UW solution, similar early decreases in cellular sodium
      and chloride contents were observed, thus excluding the possibility of the
      decreases being dependent on the preservation solution used. Furthermore,
      experiments with cultured rat hepatocytes yielded a similar decrease in sodium
      content during initiation of cold incubation in UW solution, so the decrease does
      not appear to be cell-specific either. These results suggest that, contrary to
      current opinion, sodium efflux predominates over sodium influx during the early
      phase of cold incubation of cells.

PMID- 9148737
TI  - Oxidative burst: an early plant response to pathogen infection.
AB  - As plants are confined to the place where they grow, they have to develop a broad
      range of defence responses to cope with pathogenic infections. The oxidative
      burst, a rapid, transient, production of huge amounts of reactive oxygen species
      (ROS), is one of the earliest observable aspects of a plant's defence strategy.
      First this Review describes the chemistry of ROS (superoxide radical, hydrogen
      peroxide and hydroxyl radical). Secondly, the role of ROS in defence responses is
      demonstrated, and some important issues are considered, such as: (1) which of the
      ROS is a major building element of the oxidative burst; (2) the spatial and
      temporal regulation of the oxidative burst; and (3) differences in the plant's
      responses to biotic and abiotic elicitation. Thirdly, the relationships between
      the oxidative burst and other plant defence responses are indicated. These
      include: (1) an oxygen consumption, (2) the production of phytoalexins, (3)
      systemic acquired resistance, (4) immobilization of plant cell wall proteins, (5)
      changes in membrane permeability and ion fluxes and (6) a putative role in
      hypersensitive cell death. Wherever possible, the comparisons with models
      applicable to animal systems are presented. Finally, the question of the origin
      of ROS in the oxidative burst is considered, and two major hypotheses, (1) the
      action of NADPH oxidase system analogous to that of animal phagocytes, and (2)
      the pH-dependent generation of hydrogen peroxide by a cell wall peroxidase, are
      presented. On the basis of this material, a third 'unifying' hypothesis is
      presented, where transient changes in the pH of the cell wall compartment are
      indicated as a core phenomenon in evoking ROS production. Additionally, a
      germin/oxalate oxidase system which generates H2O2 in response to pathogenic
      infection is also described.

PMID- 9148739
TI  - Studies of the esterase activity of cytosolic aldehyde dehydrogenase with
      resorufin acetate as substrate.
AB  - Resorufin acetate is a very good substrate for sheep liver cytosolic aldehyde
      dehydrogenase, both from the point of view of practical spectrophotometry and in
      terms of information provided about the nature of the catalysis shown by this
      enzyme. p-Nitrophenyl (PNP) acetate competes against resorufin acetate for the
      enzyme's active site (although relatively weakly as the latter substrate has the
      lower Michaelis constant), but acetaldehyde (in the presence of NAD+) inhibits
      the hydrolysis of resorufin acetate only at very high aldehyde concentration. In
      the absence of cofactor, the rate-limiting step in the hydrolysis of resorufin
      acetate and of PNP acetate is hydrolysis of the common acetyl-enzyme, as shown by
      the observation of bursts of chromophoric product and very similar values of
      kcat. In the presence of NAD+ or NADH, however, the deacylation step with
      resorufin acetate is greatly accelerated until acylation seems to become rate
      limiting, because no burst is seen under these conditions. Millimolar
      concentrations of Mg2+ activate the hydrolyis of resorufin acetate both in the
      presence and absence of cofactors. With both Mg2+ and cofactor the kcat for
      hydrolysis of resorufin acetate is 30-35 s-1; this is three orders of magnitude
      higher than the kcat for aldehyde oxidation in the presence of Mg2+, showing that
      the enzyme's potential catalytic efficency is very much hampered by the slowness
      with which NADH dissociates from its binding site. The pH profile for the
      hydrolysis of resorufin acetate in the presence of NAD+ or NADH fits well to a
      theoretical ionization curve of pKa approx. 8.2; it is suggested that this might
      belong to the enzyme's putative catalytic residue (Cys-302).

PMID- 9148740
TI  - Chemoattractant-induced respiratory burst: increases in cytosolic Ca2+
      concentrations are essential and synergize with a kinetically distinct second
      signal.
AB  - The role of the cytosolic free Ca2+ concentration ([Ca2+]c) and its relationship
      to other second messengers in the signalling between chemoattractant [e.g. N
      formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLP)] receptors and the NADPH
      oxidase is still poorly understood. In this study, we have used thapsigargin, an
      inhibitor of the Ca2+-ATPase of intracellular stores, as a tool to selectively
      manipulate Ca2+ release from intracellular stores and Ca2+ influx across the
      plasma membrane. We thereby temporarily separated the Ca2+ signal from other
      signals generated by fMLP and analysed the consequences on the respiratory burst.
      Under all conditions investigated, the extent of fMLP-induced respiratory burst
      activation was critically determined by [Ca2+]c elevation. fMLP was unable to
      activate the respiratory burst without [Ca2+]c elevation. Thapsigargin-induced
      Ca2+ influx activated the respiratory burst in the absence of fMLP, but only to
      approx. 20% of the values observed in the presence of fMLP. The second signal
      generated by fMLP did not activate the respiratory burst by itself, but acted in
      synergy with [Ca2+]c elevation. The second signal was long lasting (>15 min)
      provided that there was no rise in [Ca2+]c and that the receptor was continuously
      occupied. The second signal was inactivated by high [Ca2+]c elevation. Our
      results demonstrate that [Ca2+]c elevations are an essential step in the
      signalling between the fMLP receptor and NADPH oxidase. They also provide novel
      information about the properties of the second Ca2+-independent signal that
      activates the respiratory burst in synergy with [Ca2+]c.

PMID- 9148741
TI  - Characterization of a saporin isoform with lower ribosome-inhibiting activity.
AB  - We have expressed in Escherichia coli five isoforms of saporin, a single-chain
      ribosome-inactivating protein (RIP). Translation inhibition activities of the
      purified recombinant polypeptides in vitro were compared with those of
      recombinant dianthin 30, a less potent and closely related RIP, and of ricin A
      chain. Dianthin 30, and a saporin isoform encoded by a cDNA from leaf tissue (SAP
      C), both had about one order of magnitude lower activity in translation
      inhibition assays than all other isoforms of saporin tested. We recently
      demonstrated that saporin extracted from seeds of Saponaria officinalis binds to
      alpha2-macroglobulin receptor (alpha2MR; also termed low density lipoprotein
      receptor-related-protein), indicating a general mechanism of interaction of plant
      RIPs with the alpha2MR system [Cavallaro, Nykjaer, Nielsen and Soria (1995) Eur.
      J. Biochem. 232, 165-171]. Here we report that SAP-C bound to alpha2MR equally
      well as native saporin. However, the same isoform had about ten times lower
      cytotoxicity than the other saporin isoforms towards different cell lines. This
      indicates that the lower cell-killing ability of the SAP-C isoform is presumably
      due to its altered interaction with the protein synthesis machinery of target
      cells. Since saporin binding to the alpha2MR is competed by heparin, we also
      tested in cell-killing experiments Chinese hamster ovary cell lines defective for
      expression of either heparan sulphates or proteoglycans. No differences were
      observed in cytotoxicity using native saporin or the recombinant isoforms.
      Therefore saporin binding to the cell surface should not be mediated by
      interaction with proteoglycans, as is the case for other alpha2MR ligands.

PMID- 9148742
TI  - cDNA cloning and expression of the flavoprotein D-aspartate oxidase from bovine
      kidney cortex.
AB  - The isolation and sequencing of the complete cDNA coding for a d-aspartate
      oxidase, as well as the overexpression of the recombinant active enzyme, are
      reported for the first time. This 2022 bp cDNA, beside the coding portion,
      comprises a 5' untranslated tract and the whole 3' region including the
      polyadenylation signal and the poly(A) tail. The encoded protein comprises 341
      amino acids, with the last three residues (-Ser-Lys-Leu) representing a
      peroxisomal targeting signal 1 (PTS1), hitherto unknown for this protein. The
      overexpression of recombinant d-aspartate oxidase was achieved in a prokaryotic
      system, and a soluble and active enzyme was obtained which accounted for about
      10% of total bacterial protein. Comparisons with the known cDNAs for mammalian d
      amino acid oxidase, another peroxisomal enzyme, are also made. The close
      structural and functional similarities shared by these enzymes at the protein
      level are not reflected at the nucleic acid level.

PMID- 9148743
TI  - Covalent modification of nitrogenase MoFe protein by ADP.
AB  - MgADP- reacted with the nitrogenase molybdenum-iron (MoFe) protein of Klebsiella
      pneumoniae (Kp1) over a period of 2 h to yield a stable, catalytically active
      conjugate. The isolated protein exhibited a new, broad 31P NMR resonance at -1
      p.p.m. lacking phosphorus J coupling. The adenine ring of [8-14C]ADP remained
      associated with the conjugate. A covalently bound nucleotide was identified as
      AMP by NMR and TLC. Extended dialysis of Kp1 against MgADP- resulted in further
      AMP binding at the protein surface. ADP was initially bound tightly to Kp1 at a
      site distinct from the AMP sites. ATP did not replace ADP. The time course of the
      formation of the Kp1-AMP was altered by the nitrogenase iron protein (Kp2) and
      was dependent on redox potential. Kp1-AMP was stable to concentration and
      oxidation with ferricyanide ion at -350 mV. Slow hydrolysis of Kp1-AMP over a
      period of 6 h yielded AMP and unaltered Kp1. The adenine ring of ADP exchanged
      with adenine of MgATP2- during reductant-limited turnover of nitrogenase under
      N2, indicating reversibility of ATP hydrolysis at 15 degrees C. [32P]Pi exchanged
      with the terminal phosphate group of both ADP and ATP on incubation with Kp1. 32P
      exchange and the catalytic activity of Kp1 were inhibited by a 20-fold molar
      excess of the lysine-modifying reagent, o-phthalaldehyde (OPT). Preincubation
      with MgADP- protected against OPT inactivation. Two potentially reactive lysine
      residues on the alpha chain of the MoFe protein near a putative hydrophobic
      docking site for the nitrogenase Fe protein are proposed as sites of OPT and
      nucleotide binding. Azotobacter vinelandii MoFe protein (Av1) also formed an AMP
      adduct but Kp2 did not. Catalase did not interact with ADP. The reactions of the
      nitrogenase MoFe protein with adenine nucleotides have no counterpart in known
      protein-nucleotide interactions.

PMID- 9148744
TI  - Glucose-induced glycogenesis in the liver involves the glucose-6-phosphate
      dependent dephosphorylation of glycogen synthase.
AB  - Non-metabolized glucose derivatives may cause inactivation of phosphorylase but,
      unlike glucose, they are unable to elicit activation of glycogen synthase in
      isolated hepatocytes. We report here that, after the previous inactivation of
      phosphorylase by one of these glucose derivatives (2-deoxy-2-fluoro-alpha
      glucosyl fluoride), glycogen synthase was progressively activated by addition of
      increasing concentrations of glucose. Under these conditions, the degree of
      activation of glycogen synthase was linearly correlated with the intracellular
      glucose-6-phosphate (Glc-6-P) concentration. Addition of glucosamine, an
      inhibitor of glucokinase, decreased both parameters in parallel. Further
      experiments using an inhibitor of either protein kinases (5-iodotubercidin) or
      protein phosphatases (microcystin) in isolated hepatocytes indicated that Glc-6-P
      does not affect glycogen-synthase kinase activity but enhances the glycogen
      synthase phosphatase reaction. Experiments in vitro showed that the synthase
      phosphatase activity of glycogen-bound type-1 protein phosphatase was increased
      by physiological concentrations of Glc-6-P (0.1-0.5 mM), but not by 2.5 mM
      fructose-6-P, fructose-1-P or glucose-1-P. At physiological ionic strength, the
      glycogen-associated synthase phosphatase activity was nearly entirely Glc-6-P
      dependent, but Glc-6-P did not relieve the strong inhibitory effect of
      phosphorylase a. The large stimulatory effects of 2.5 mM Glc-6-P, with glycogen
      synthase b and phosphorylase a as substrates, appeared to be mostly substrate
      directed, while the modest effects observed with casein and histone IIA pointed
      to an additional stimulation of glycogen-bound protein phosphatase-1 by Glc-6-P.
      We conclude that glucose elicits hepatic synthase phosphatase activity both by
      removal of the inhibitor, phosphorylase a, and by generation of the stimulator,
      Glc-6-P.

PMID- 9148745
TI  - Retinol and retinaldehyde specifically increase alpha1-proteinase inhibitor in
      the human cornea.
AB  - alpha1-Proteinase inhibitor is a serpin and can inhibit most serine proteinases.
      The cornea is one of several extrahepatic tissues that synthesizes this
      inhibitor. In the presence of retinol, corneal alpha1-proteinase inhibitor levels
      were increased 3.8-fold. The maximal response was achieved 2 h after the addition
      of retinol (1 microM final concentration) to the culture medium. A similar
      increase in alpha1-proteinase inhibitor was observed with retinaldehyde (1 nM
      final concentration). Concentrations of alpha1-proteinase inhibitor in other
      tested cells (Hep G2, CaCo 2, MCF-7, monocytes and macrophages) remained
      unchanged in the presence of retinol. Retinoic acid did not affect alpha1
      proteinase inhibitor levels in the cornea or the other cells tested. The acute
      phase cytokine, interleukin-6, increased alpha1-proteinase inhibitor levels in
      all tested tissues/cells except the cornea. These results demonstrate that alpha1
      proteinase inhibitor levels are controlled differently in the cornea compared
      with other tissues/cells. alpha1-Proteinase inhibitor is the first protein
      identified whose levels are regulated by a mechanism supported by retinol and
      retinaldehyde but not retinoic acid.

PMID- 9148746
TI  - Biochemical characterization of the protein tyrosine kinase homology domain of
      the ErbB3 (HER3) receptor protein.
AB  - The putative protein tyrosine kinase domain (TKD) of the ErbB3 (HER3) receptor
      protein was generated as a histidine-tagged recombinant protein (hisTKD-B3) and
      characterized enzymologically. CD spectroscopy indicated that the hisTKD-B3
      protein assumed a native conformation with a secondary structure similar to that
      of the epidermal growth factor (EGF) receptor TKD. However, when compared with
      the EGF receptor-derived protein, hisTKD-B3 exhibited negligible intrinsic
      protein tyrosine kinase activity. Immune complex kinase assays of full-length
      ErbB3 proteins also yielded no evidence of catalytic activity. A fluorescence
      assay previously used to characterize the nucleotide-binding properties of the
      EGF receptor indicated that the ErbB3 protein was unable to bind nucleotide. The
      hisTKD-B3 protein was subsequently found to be an excellent substrate for the EGF
      receptor protein tyrosine kinase, which suggested that in vivo phosphorylation of
      ErbB3 in response to EGF could be attributed to a direct cross-phosphorylation by
      the EGF receptor protein tyrosine kinase.

PMID- 9148747
TI  - Reduced beta-strand content in apoprotein B-100 in smaller and denser low-density
      lipoprotein subclasses as probed by Fourier-transform infrared spectroscopy.
AB  - The secondary structure of apolipoprotein B-100 in low-density lipoprotein (LDL)
      subfractions was analysed by Fourier-transform IR spectroscopy. LDLs were
      isolated in three density ranges by gradient centrifugation of human plasma from
      healthy volunteers. The spectra revealed differences in the lipid content and
      composition of the three LDL fractions. The secondary structure of apolipoprotein
      B-100 was the same in the two fractions corresponding to the large less-dense LDL
      particles, whereas a lower content of beta-strands was found in the third
      fraction corresponding to the smaller denser LDL particles. Analysis of the
      spectroscopic data suggests that, in the same set of LDL subfractions, the
      particle size is probably the cause of the observed differences in apolipoprotein
      B-100 secondary structure.

PMID- 9148748
TI  - Recombinant expression and isolation of human L-arginine:glycine
      amidinotransferase and identification of its active-site cysteine residue.
AB  - Creatine and its phosphorylated form play a central role in the energy metabolism
      of muscle and nerve tissues. l-Arginine:glycine amidinotransferase (AT) catalyses
      the committed step in the formation of creatine. The mitochondrial and cytosolic
      forms of the enzyme are believed to derive from the same gene by alternative
      splicing. We have expressed recombinant human AT in Escherichia coli with two
      different N-termini, resembling the longest two forms of the enzyme that we had
      isolated recently from porcine kidney mitochondria as a mixture. The enzymes were
      expressed with N-terminal histidine tags followed by factor Xa-cleavage sites. We
      established a new method for the removal of N-terminal fusion peptides by means
      of an immobilized snake venom prothrombin activator. We identified cysteine-407
      as the active-site residue of AT by radioactive labelling and isolation of
      labelled peptides, and by site-directed mutagenesis of the protein.

PMID- 9148749
TI  - Differential expression of ryanodine receptor RyR2 mRNA in the non-pregnant and
      pregnant human myometrium.
AB  - We describe here the expression of the ryanodine receptor isoforms RyR2 and RyR3
      in human non-pregnant and pregnant (non-labouring) myometrium, and in isolated
      cultured myometrial cells. The mRNA encoding the RyR3 isoform was found in both
      non-pregnant and pregnant myometrial tissue samples; however, the mRNA for RyR2
      was found only in pregnant samples. It can be speculated that the appearance of
      this additional isoform in the pregnant myometrium may increase the ability of
      this tissue to contract at term. Control of expression of the RyR2 gene may
      therefore be another example of an up-regulated signalling system in pregnancy.
      Although the mRNA for RyR3 was expressed in cultured myometrial cells, the mRNA
      for RyR2 could not be detected. Thus cultured myometrial cells appear to be
      similar to the non-pregnant myometrium. The cytokine transforming growth factor
      beta (TGF-beta) has been reported to alter RyR mRNA expression in many cell
      types. After treatment with TGF-beta, both RyR2 and RyR3 mRNAs could be detected
      in cultured myometrial cells. These observations support the idea that the
      expression of the RyR2 isoform is up-regulated both in pregnancy and in TGF-beta
      treated cultured myometrial cells. Using measurements of 45Ca2+ release, we have
      further demonstrated that cultured human myometrial cells show a significant
      augmentation of both the Ca2+-induced Ca2+ release (CICR) mechanism and ryanodine
      induced Ca2+ release after treatment with TGF-beta. Additionally, caffeine was
      able to induce Ca2+ release and sensitize the CICR mechanism to ryanodine. Thus
      we suggest that the appearance of RyR2 mRNA leads to the expression of this
      receptor/channel protein with identifiable pharmacological characteristics. These
      results are discussed in the context of the potential role of gene activation in
      the process of maturation of the human myometrium during pregnancy.

PMID- 9148750
TI  - Cytoplasmic Ca2+ signalling and reduction of mitochondrial pyridine nucleotides
      in adrenal glomerulosa cells in response to K+, angiotensin II and vasopressin.
AB  - We have examined the mitochondrial formation of NAD(P)H in rat adrenal
      glomerulosa cells. A short-term elevation of the K+ concentration from 3.6 to 8.4
      mM induced a reversible increase in the formation of reduced pyridine
      nucleotides. Potassium applied after the addition of rotenone had no further
      effect, confirming that the redox signal was of mitochondrial origin. Inhibition
      of aldosterone synthesis by aminoglutethimide in K+-stimulated cells decreased
      the rate of decay of the NAD(P)H signal upon the termination of stimulation,
      indicating that the NADPH formed was consumed in aldosterone synthesis. When the
      NAD(P)H signal was measured simultaneously with the cytoplasmic free Ca2+
      concentration ([Ca2+]i), elevation of the K+ concentration to 6.6 or 8.4 mM
      induced parallel increases in [Ca2+]i and NAD(P)H formation. The rates of
      increase and decrease of NAD(P)H were lower than for [Ca2+]i, confirming that the
      redox signal was secondary to the Ca2+ signal. Angiotensin II (100 pM-1 nM)
      induced an oscillatory NAD(P)H signal which usually returned to a lower baseline
      concentration, while a sustained signal with superimposed oscillations was
      observed at higher concentrations. Simultaneous measurements showed that NAD(P)H
      levels followed the [Ca2+]i pattern evoked by angiotensin II. Vasopressin (100
      nM) also induced parallel oscillations of [Ca2+]i and NAD(P)H. A sustained rise
      in the extramitochondrial Ca2+ concentration to 1 microM induced a sustained
      elevation of the intramitochondrial Ca2+ concentration in permeabilized cells, as
      measured with rhod-2. A sustained rise in [Ca2+]i evoked by long-term stimulation
      with 8.4 mM K+ or 2.5 nM angiotensin II resulted in sustained NAD(P)H production.
      These Ca2+-dependent changes in the mitochondrial redox state support the
      biological response, i.e. aldosterone secretion by glomerulosa cells.

PMID- 9148751
TI  - Study of the interactions of cadmium and zinc ions with cellular calcium
      homoeostasis using 19F-NMR spectroscopy.
AB  - The effects of the heavy-metal ions Cd2+ and Zn2+ on the homoeostasis of
      intracellular free Ca2+ in E367 neuroblastoma cells were examined using 19F-NMR
      spectroscopy with the fluorinated chelator probe 1,2-bis-(2-amino-5
      fluorophenoxy)ethane-N,N,N', N'-tetra-acetic acid (5F-BAPTA). First, the
      technique was used to quantify the uptake and intracellular free concentrations
      of the heavy metals after treatment of the cells with 20 microM CdCl2 or 100
      microM ZnCl2. Secondly, metal-induced transients in intracellular free Ca2+ were
      recorded. Addition of 20 microM CdCl2, but not 100 microM ZnCl2, evoked a
      transient increase in Ca2+ from a resting level of 84 nM to approx. 190 nM within
      15 min after addition of the metal. Zn2+ at 20 microM completely prevented the
      induction of a Ca2+ transient by Cd2+. Ca2+ was mobilized by Cd2+ from
      intracellular organelles, since depletion of these stores by thapsigargin
      abolished the effect of the toxic metal. Furthermore, 20 microM Cd2+ evoked a
      transient rise in cellular Ins(1,4,5)P3, reaching a maximum level within 5 min
      after addition of the metal. These results demonstrate that perturbation of the
      Ins(1,4,5)P3/Ca2+ messenger system is an early and discrete cellular effect of
      Cd2+.

PMID- 9148752
TI  - Identification and characterization of a novel A-kinase-anchoring protein
      (AKAP120) from rabbit gastric parietal cells.
AB  - The type-II cAMP-dependent protein kinase (A-Kinase) partitions primarily into
      the particulate fraction in gastric parietal cells. Localization of this kinase
      to particular subcellular domains is mediated through the binding of the
      regulatory subunit (RII) dimer to A-Kinase-anchoring proteins (AKAPs). Using a
      [32P]RII overlay assay, we have screened a rabbit gastric parietal cell cDNA
      library and have isolated a single RII-binding protein clone. Sequence analysis
      revealed an open reading frame coding for 1022 amino acids (AKAP120). Recombinant
      fragments of the full-length clone were prepared and the RII-binding region
      mapped to an area between amino acids 489 and 549. This area contained a putative
      alpha-helical RII-binding region between amino acids 503 and 516. Incubation of
      [32P]RII with a synthetic peptide of AKAP120-(489-522) completely inhibited the
      binding of [32P]RII to the recombinant AKAP120 fragments that demonstrated RII
      binding. In vitro RII-binding affinity studies indicated a high-affinity
      interaction between AKAP120 and RII with a Kapp between 50 and 120 nM for the
      three recombinant fragments that bound [32P]RII. RNase-protection analysis
      revealed that AKAP120 is a widely distributed protein, with the highest levels of
      mRNA observed in gastric fundus. The presence of this novel high-affinity AKAP in
      gastric parietal cells suggests that it may regulate RII subcellular
      sequestration in this cell type.

PMID- 9148753
TI  - Degradation of decorin by matrix metalloproteinases: identification of the
      cleavage sites, kinetic analyses and transforming growth factor-beta1 release.
AB  - Decorin (DCN) is a ubiquitous proteoglycan comprised of a core protein attached
      to a single dermatan/chondroitin sulphate glycosaminoglycan chain. It may play a
      role in regulation of collagen fibrillogenesis and function as a reservoir of
      transforming growth factor beta (TGF-beta) in the extracellular milieu. We have
      examined the susceptibility of DCN to five different matrix metalloproteinases
      (MMPs): MMP-1 (tissue collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin 1),
      MMP-7 (matrilysin) and MMP-9 (gelatinase B). MMP-2 and MMP-3 digest DCN into
      seven major fragments in a similar pattern. The N-terminal sequence of the two
      fragments generated by MMP-2 and MMP-3 is Leu211-Lys-Gly-Leu-Asn, but that of the
      others is Asp1-Glu-Ala-Ser-Gly. MMP-7 cleaves DCN into three major fragments
      which have the N-termini Asp1-Glu-Ala-Ser-Gly, Glu2-Ala-Ser-Gly-Ile and Leu244
      His-Leu-Asp-Asn. Activities of MMP-1 and MMP-9 against DCN are negligible. The
      values of Km for the MMPs capable of degrading DCN are very similar (10-12
      microM), but the kcat/Km value for MMP-7 (30.5 microM-1.h-1) is 4.5-fold higher
      than those for MMP-2 and MMP-3. Incubation of a DCN-TGF-beta1 complex with MMP-2,
      -3 or -7 results in release of TGF-beta1 from the complex. These data indicate
      proteolytic degradation of DCN by MMP-2, MMP-3 and MMP-7, and suggest the
      possibility that, under pathophysiological conditions, the digestion by the MMPs
      may induce tissue reactions mediated by TGF-beta1 released from DCN in the
      connective tissues.

PMID- 9148754
TI  - Heterologous expression and characterization of wild-type and mutant forms of a
      26 kDa endochitinase from barley (Hordeum vulgare L.).
AB  - To investigate structure-function relationships in plant chitinases, we have
      developed a heterologous expression system for the 26 kDa endochitinase from
      Hordeum vulgare L. (barley). Escherichia coli cells harbouring the gene in a T7
      RNA polymerase-based expression vector synthesized completely insoluble
      recombinant protein under standard induction conditions at 37 degrees C. However,
      a concentration of soluble recombinant protein of approx. 15 mg/l was achieved by
      inducing bacteria at low temperature (15 degrees C). Recombinant endochitinase
      was purified to homogeneity and shown to be structurally and functionally
      identical to the seed protein. An average of three disulphide bonds are present
      in the recombinant enzyme, consistent with the number found in the natural form.
      The seed and recombinant proteins showed the same specific activity towards a
      high-molecular-mass substrate and exhibited similar anti-fungal activity towards
      Tricoderma reesei. Site-directed mutagenesis was used to replace residues that
      are likely to be involved in the catalytic event, based on structural
      similarities with lysozyme and on sequence alignments with related chitinases.
      The Glu67-->Gln mutation resulted in a protein with undetectable activity, while
      the Glu89-->Gln mutation yielded an enzyme with 0. 25% of wild-type specific
      activity. This suggests that two acidic residues are essential for catalytic
      activity, similar to the situation with many other glycosyl hydrolases.
      Examination of conserved residues stretching into the proposed substrate binding
      cleft suggests that Asn124 also plays an important functional role.

PMID- 9148755
TI  - Glucose-independent inhibition of yeast plasma-membrane H+-ATPase by calmodulin
      antagonists.
AB  - Glucose metabolism causes activation of the yeast plasma-membrane H+-ATPase. The
      molecular mechanism of this regulation is not known, but it is probably mediated
      by phosphorylation of the enzyme. The involvement in this process of several
      kinases has been suggested but their actual role has not been proved. The
      physiological role of a calmodulin-dependent protein kinase in glucose-induced
      activation was investigated by studying the effect of specific calmodulin
      antagonists on the glucose-induced ATPase kinetic changes in wild-type and two
      mutant strains affected in the glucose regulation of the enzyme. Preincubation of
      the cells with calmidazolium or compound 48/80 impeded the increase in ATPase
      activity by reducing the Vmax of the enzyme without modifying the apparent
      affinity for ATP in the three strains. In one mutant, pma1-T912A, the putative
      calmodulin-dependent protein kinase-phosphorylatable Thr-912 was eliminated, and
      in the other, pma1-P536L, H+-ATPase was constitutively activated, suggesting that
      the antagonistic effect was not mediated by a calmodulin-dependent protein kinase
      and not related to glucose regulation. This was corroborated when the in vitro
      effect of the calmodulin antagonists on H+-ATPase activity was tested. Purified
      plasma membranes from glucose-starved or glucose-fermenting cells from both pma1
      P890X, another constitutively activated ATPase mutant, and wild-type strains were
      preincubated with calmidazolium or melittin. In all cases, ATP hydrolysis was
      inhibited with an IC50 of approximately 1 microM. This inhibition was reversed by
      calmodulin. Analysis of the calmodulin-binding protein pattern in the plasma
      membrane fraction eliminates ATPase as the calmodulin target protein. We conclude
      that H+-ATPase inhibition by calmodulin antagonists is mediated by an as yet
      unidentified calmodulin-dependent membrane protein.

PMID- 9148756
TI  - The role of NAD+ as a signal during nitrogenase switch-off in Rhodospirillum
      rubrum.
AB  - The role of NAD+ in the metabolic regulation of nitrogenase, the 'switch-off'
      effect, in Rhodospirillum rubrum has been studied. We now show that the decrease
      in nitrogenase activity upon addition of NAD+ to R. rubrum is due to modification
      of dinitrogenase reductase. There was no effect when NAD+ was added to a mutant
      of R. rubrum devoid of dinitrogenase reductase ADP-ribosyltransferase, indicating
      that NAD+ 'switch-off' is an effect of the same regulatory system as ammonium
      'switch-off'. We also show that oxaloacetate and alpha-ketoglutarate function as
      'switch-off' effectors. On the other hand beta-hydroxybutyrate has the opposite
      effect by shortening the 'switch-off' period. Furthermore, by using an inhibitor
      of glutamate synthase the role of this enzyme in 'switch-off' was investigated.
      The results are discussed in relation to our proposal that changes in the
      concentration of NAD+ are involved in initiating 'switch-off'.

PMID- 9148757
TI  - Regulation of lactase-phlorizin hydrolase gene expression by the caudal-related
      homoeodomain protein Cdx-2.
AB  - Lactase-phlorizin hydrolase is exclusively expressed in the small intestine and
      is often used as a marker for the differentiation of enterocytes. The cis-element
      CE-LPH1 found in the lactase-phlorizin hydrolase promoter has previously been
      shown to bind an intestinal-specific nuclear factor. By electrophoretic mobility
      shift assay it was shown that the factor Cdx-2 (a homoeodomain-protein related to
      caudal) binds to a TTTAC sequence in the CE-LPH1. Furthermore it was demonstrated
      that Cdx-2 is able to activate reporter gene transcription by binding to CE-LPH1.
      A mutation in CE-LPH1, which does not affect Cdx-2 binding, results in a higher
      transcriptional activity, indicating that the CE-LPH1 site contains other binding
      site(s) in addition to the Cdx-2-binding site.

PMID- 9148758
TI  - Benzyloxycarbonylprolylprolinal, a transition-state analogue for prolyl
      oligopeptidase, forms a tetrahedral adduct with catalytic serine, not a reactive
      cysteine.
AB  - N-Benzyloxycarbonyl-l-prolyl-l-[1-13C]prolinal was synthesized starting with
      reduction of l-[1-13C]Pro to l-[1-13C]prolinol, followed by coupling with N
      benzyloxycarbonyl-l-Pro to N-benzyloxycarbonyl-l-Pro-l-[1-13C]prolinol (Z-Pro-[1
      13C]prolinol), and finally oxidation of the alcohol to the aldehyde with dimethyl
      sulphoxide. While the 13C NMR chemical shift of the aldehyde carbon is 202
      p.p.m., that of the aldehyde hydrate is between 91.6 and 91.8 p.p.m., that of the
      dithiothreitol adduct is between 74.8 and 75.0 p. p.m., and that in the presence
      of the serine protease prolyl oligopeptidase is at 92.3 p.p.m.. The linewidth of
      the latter is 114 Hz, roughly consistent with the molecular mass of 80 kDa
      reported for the enzyme. Inverse detection experiments gave a 1H resonance at
      5.29 p.p.m. with a linewidth of 80 Hz, also consistent with the expected chemical
      shift and linewidth for a hemiacetal bound to such a large enzyme, while the free
      hydrate gave resonances at 5.18 and 5. 25 p.p.m., with very much narrower
      linewidths. It is concluded that Z-Pro-prolinal, a putative transition-state
      analogue for prolyl oligopeptidase, forms a tetrahedral complex with the enzyme
      at its catalytic serine, rather than at a neighbouring cysteine that was found to
      be highly reactive according to chemical modification studies.

PMID- 9148759
TI  - New alpha-L-arabinofuranosidase produced by Streptomyces lividans: cloning and
      DNA sequence of the abfB gene and characterization of the enzyme.
AB  - A fully secreted alpha-l-arabinofuranosidase was cloned from the homologous
      expression system of Streptomyces lividans. The gene, located upstream adjacent
      to the previously described xylanase A gene, was sequenced. It is divergently
      transcribed from the xlnA gene and the two genes are separated by an
      intercistronic region of 391nt which contains a palindromic AT-rich sequence. The
      deduced amino acid sequence of the protein shows that the enzyme contains a
      distinct catalytic domain which is linked to a specific xylan-binding domain by a
      linker region. The purified enzyme has a specific arabinofuranose-debranching
      activity on xylan from Gramineae, acts synergistically with the S. lividans
      xylanases and binds specifically to xylan. From small arabinoxylo-oligosides, it
      liberates arabinose and, after prolonged incubation, the purified enzyme exhibits
      some xylanolytic activity as well.

PMID- 9148760
TI  - Activation of the ATPase activity of heat-shock proteins Hsc70/Hsp70 by cysteine
      string protein.
AB  - DnaJ proteins are characterized by a 'J' domain which is homologous to a region
      of the Escherichia coli protein DnaJ. DnaJ has been shown to interact with the
      chaperone protein DnaK, and a number of eukaryotic DnaJ-like proteins have been
      found to interact with the 70 kDa heat-shock protein/70 kDa heat-shock cognate
      protein (Hsp70/Hsc70), the eukaryotic homologues of DnaK. Cysteine-string
      proteins (Csps) are believed to function in calcium-stimulated exocytosis and in
      this paper we describe a specific ATP-dependent interaction between a Csp (Csp1)
      and Hsc70/Hsp70. We also show that Csp1 can stimulate the ATPase activity of both
      Hsc70 and Hsp70 several-fold. Furthermore, we demonstrate that Csp2, a Csp
      variant found in adrenal chromaffin cells, can enhance the ATPase activity of
      Hsc70 to a similar extent as Csp1, whereas Csp(137-198), a truncated protein
      lacking the 'J' domain of Csp1 is unable to stimulate the ATPase activity of
      Hsc70. This suggests that the functions of Csp1 and Csp2 must differ in some
      aspect other than interaction with Hsc70. This study is also important from a
      general view of DnaJ/Hsc70 interactions, as Csps lack a G/F-rich region which has
      been suggested to be essential for activation of the ATPase activity of DnaK by
      DnaJ. Thus, this work would imply that a G/F-rich region is not an essential
      feature of DnaJ proteins for stimulation of the ATPase activity of Hsp70
      proteins.

PMID- 9148761
TI  - Rifampicin inhibits the toxicity of pre-aggregated amyloid peptides by binding to
      peptide fibrils and preventing amyloid-cell interaction.
AB  - Rifampicin and its analogues, p-benzoquinone and hydroquinone, inhibited the
      toxicity of preformed aggregates of human islet amyloid polypeptide, amylin, to
      rat pheochromocytoma PC12 cells, when preincubated with the aggregated peptide
      before addition to cell cultures. Immunofluorescence microscopy showed that they
      prevented the adhesion of amylin aggregates to the cell surface, and this effect
      was induced probably by their binding to peptide fibrils during preincubation.
      Other quinone derivatives, i.e., p-methoxyphenol, AA-861 and idebenone, failed to
      inhibit the toxicity and cell-surface adhesion of amylin aggregates. Rifampicin
      analogues also inhibited the toxicity of pre-aggregated amyloid beta1-42
      peptides, suggesting a common toxic mechanism of different amyloid peptides and
      their therapeutic potential for several amyloidoses.

PMID- 9148762
TI  - Structure and organization of amplicons containing the E4 esterase genes
      responsible for insecticide resistance in the aphid Myzus persicae (Sulzer).
AB  - Insecticide resistance in the aphid Myzus persicae results primarily from the
      amplification of genes encoding the insecticide-detoxifying esterase, E4. Here we
      report the analysis of flanking DNA co-amplified with the E4 gene. The 5' end of
      this gene has an untranslated leader sequence interspersed by two introns, and
      the promoter region lacks TATA and CAAT boxes. The DNA breakpoint involved in the
      generation of the amplification is just upstream (approx. 250 bp) of the putative
      E4 transcription start site; thus the E4 gene is very close to the 5' end of the
      approx. 24 kb amplicon. PCR primers specific to the 'novel joint' generated
      during the amplification have been used to show that a wide range of aphid clones
      have the same amplicons, arranged as a series of head-to-tail direct repeats.
      Long-distance mapping has revealed the structure of these repeats. This has
      important implications for understanding both the generation of the amplified
      genes and the origin and spread of insecticide resistance in M. persicae.

PMID- 9148763
TI  - Interaction of Nck-associated protein 1 with activated GTP-binding protein Rac.
AB  - Bacterially expressed glutathione S-transferase fusion proteins containing Rac1
      were used to identify binding proteins of this Rho family GTPase present in a
      bovine brain extract. Five proteins of 85, 110, 125, 140 and 170 kDa were
      detected, all of which were associated exclusively with guanosine 5'-[gamma
      thio]triphosphate-bound Rac1, not with GDP-bound Rac1. The 85 and 110 kDa
      proteins were identified as the regulatory and catalytic subunits respectively of
      phosphatidylinositol 3-kinase. Several lines of evidence suggested that the 125
      kDa protein is identical with Nck-associated protein 1 (Nap1). The mobilities of
      the 125 kDa protein and Nap1 on SDS/PAGE were indistinguishable, and the 125 kDa
      protein was depleted from brain extract by preincubation with the Src homology 3
      domain of Nck to which Nap1 binds. Furthermore, antibodies to Nap1 reacted with
      the 125 kDa protein. Nap1 was co-immunoprecipitated with a constitutively active
      form of Rac expressed in Chinese hamster ovary cells. The observation that
      complex formation between activated Rac and PAK, but not that between Rac and
      Nap1, could be reproduced in vitro with recombinant proteins indicates that the
      interaction of Nap1 with Rac is indirect. The 140 kDa Rac-binding protein is a
      potential candidate for a link that connects Nap1 to Rac. The multimolecular
      complex comprising Rac, Nap1 and probably the 140 kDa protein might mediate some
      of the biological effects transmitted by the multipotent GTPase.

PMID- 9148764
TI  - Mechanism of cysteine protease inactivation by peptidyl epoxides.
AB  - Peptidyl epoxides are time- and concentration-dependent selective cysteine
      protease inhibitors. The lack of recovery of enzymic activity and the retention
      of 1 molar equivalent of radioactive inhibitor associated with the enzyme on
      dialysis, shown in this study, indicate that they form a covalent irreversible
      equimolar complex with the enzyme. It is also shown that the peptidyl epoxide
      inhibitors alkylate the active-site thiol. This alkylation only occurs when the
      enzyme is in its native conformation, as the denatured enzyme does not undergo
      alkylation by the inhibitor to any appreciable extent. Finally, the inactivation
      process is compared with a model reaction between a peptidyl epoxide and a
      protected cysteine in neutral and basic aqueous media. The inactivation of
      cathepsin B by Cbz-Phe-(O-benzyl)-Thr-epoxide is accelerated by 5.5 orders of
      magnitude relative to the rate of the model reaction at pH 10.0 and 25 degrees C,
      and estimated to be at least 10(8) times faster than the model reaction at pH
      7.0. These results, in conjunction with the selectivity exhibited by peptidyl
      epoxides at all levels, point to a mechanism-based inhibition, and may have
      mechanistic implications regarding the catalysis carried out by cysteine
      proteases.

PMID- 9148765
TI  - Sequence elements surrounding the acceptor site suppress alternative splicing of
      the sarco/endoplasmic reticulum Ca2+-ATPase 2 gene transcript.
AB  - Expression of the muscle-specific 2a isoform of the sarco/endoplasmic reticulum
      Ca2+-ATPase (SERCA2) requires activation of an inefficient optional splice
      process at the 3' end of the primary gene transcript. The sequence elements
      required for this regulated splice event were studied by modifying a minigene
      containing the 3' end of the SERCA2 gene. An important requirement appears to be
      a strong muscle-specific acceptor site, as replacing it by a weak one prevented
      the induction of muscle-type splicing during myogenic differentiation. The
      induction of muscle-type splicing did not depend on positive cis-active sequences
      in the muscle-specific exon. On the other hand, replacement of a broad region
      around the acceptor site dramatically deregulated the expression pattern, as this
      modification strongly induced muscle-type splicing in undifferentiated muscle
      cells and in fibroblasts. This cis-active region is also involved in the
      suppression of the neuronal type of splicing. Furthermore selective replacement
      of the acceptor site as well as deletions or replacements in the muscle-specific
      exon induced muscle-type splicing to various extents in undifferentiated myogenic
      cells. Therefore sequence elements in the distal part of the optional intron and
      in the muscle-specific exon contribute to the suppression of muscle-specific
      SERCA2 splicing.

PMID- 9148767
TI  - An enhancer with cell-type dependent activity is located between the myeloid and
      epithelial aminopeptidase N (CD 13) promoters.
AB  - The 5' flanking region of the gene encoding the small intestinal brush-border
      peptidase aminopeptidase N (APN) was screened for the presence of enhancer
      regions. A 300 bp region with enhancer activity was identified 2.7 kb upstream of
      the transcriptional start site which is used in epithelial cells. The enhancer
      stimulated transcription from a heterologous promoter (the simian virus 40 early
      promoter) in a position- and orientation-independent manner. The activity of the
      enhancer is cell-type dependent and it is active in liver (HepG2), intestinal
      (Caco-2) and myeloid (K562) cells. As the epithelial APN promoter is active in
      the first two cell-types and the myeloid APN promoter in the last, the results
      may suggest that the enhancer, through a cooperation with either of the
      promoters, is important for the tissue-specific expression of APN. A detailed
      analysis of the enhancer led to the identification of four functionally important
      regions that are protected against DNase I digestion by Caco-2 nuclear extract.
      Sequence analysis suggests that two of the regions may interact with members of
      the Ets transcription factor family (Ets is a transformation-specific protein
      first discovered in the E26 avian erythroblastosis virus), one region with a
      CCAAT enhancer-binding protein and one region with Sp1, a transcriptional
      activator first described as a factor binding to the simian virus 40 early
      promoter.

PMID- 9148766
TI  - Secretory processing of amyloid precursor protein is inhibited by increase in
      cellular cholesterol content.
AB  - Plasma-membrane composition plays a crucial role in most of the cellular
      functions that depend on membrane processes. In virtually all cell types the
      proteolytic processing of Alzheimer amyloid precursor protein (APP) to generate
      soluble APP (sAPP) is believed to occur at the plasma membrane or in its
      immediate proximity. Alteration of this metabolic pathway has been linked to the
      pathogenesis of Alzheimer's disease. We analysed the effect of membrane
      cholesterol enrichment on APP metabolism. Incubation of COS cells with increasing
      concentrations of non-esterified cholesterol carried by rabbit beta-very low
      density lipoprotein caused a dose-dependent inhibition of sAPP release: 70%
      inhibition with 10 microg/ml non-esterified cholesterol. A less pronounced
      inhibitory effect was observed on treatment with human low-density lipoprotein.
      Inhibition of sAPP release was independent of receptor-mediated lipoprotein
      metabolism since simultaneous treatment with chloroquine did not modify the
      effect of lipoprotein treatment. In addition, treatment with cholesterol
      dissolved in either ethanol or methyl-beta-cyclodextrin elicited the same effect.
      Excess non-esterified cholesterol did not cause cell toxicity. Cell cholesterol
      mass inversely correlated with sAPP release. Progesterone, which inhibits
      shuttling of non-esterified cholesterol between the plasma membrane and
      intracellular pools, had no effect on the inhibition of sAPP release from
      cholesterol-loaded cells, providing indirect evidence that cholesterol may act at
      the plasma membrane.

PMID- 9148768
TI  - ATP depletion inhibits glucocorticoid-induced thymocyte apoptosis.
AB  - In quiescent thymocytes, mitochondrial de-energization was not correlated to
      apoptotic death. In fact, thymocytes treated with oligomycin, a highly specific
      inhibitor of ATP synthase, alone or with atractyloside to block ATP translocation
      from the cytoplasm, were alive, even if their mitochondria were depolarized, as
      revealed by flow cytometry after Rhodamine 123 staining. Furthermore, oligomycin
      was a powerful inhibitor of apoptosis induced in rat thymocytes by dexamethasone
      and, to a lesser extent, by the calcium ionophore A23187 and etoposide, but was
      without effect when apoptosis was induced by staurosporine, and increased cell
      death in mitogen-treated thymocytes. The inhibition of apoptosis was confirmed by
      morphological criteria, inhibition of inter-nucleosomal DNA fragmentation and
      inhibition of the loss of membrane integrity. The anti-apoptotic effect of
      oligomycin in cells treated with A23187 or etoposide was correlated to the
      inhibition of protein synthesis, while inhibition of apoptosis induced by
      dexamethasone, already evident at an oligomycin concentration of 10 ng/ml, was
      instead strictly correlated to the effect exerted on the cellular ATP level.
      Thymocyte apoptosis triggered by dexamethasone was blocked or delayed by
      inhibitors of respiratory-chain uncouplers, inhibitors of ATP synthase and
      antioxidants: a lasting protection from dexamethasone-induced apoptosis was
      always correlated to a drastic and rapid reduction in ATP level (31-35% of
      control), while a delay in the death process was characterized by a moderate
      decrease in ATP (73-82% of control). Oligomycin inhibited the specific binding of
      radioactive corticosteroid to thymocyte nuclei, confirming the inhibitory effect
      of ATP depletion on glucocorticoid binding and suggesting that ATP depletion is a
      common mediator of the anti-apoptotic action of different effectors in
      glucocorticoid-induced apoptosis. In conclusion, the reported data indicate that
      ATP may act as a cellular modulator of some forms of apoptosis, depending on the
      death trigger, and that in quiescent cells the de-energization of mitochondria is
      not necessarily linked to apoptosis.

PMID- 9148769
TI  - Antibody selection against CD52 produces a paroxysmal nocturnal haemoglobinuria
      phenotype in human lymphocytes by a novel mechanism.
AB  - The CD52 antigen is a lymphocyte glycoprotein with an extremely short polypeptide
      backbone and a single N-linked glycan, and it is attached to the cell membrane by
      a glycosylphosphatidylinositol (GPI) anchor. Treatment of rheumatoid arthritis
      patients with CAMPATH-1H, a humanized monoclonal antibody against CD52, resulted,
      in a small number of cases, in the appearance and persistence of CD52-negative T
      cells. Similarly, CD52-negative B cells emerged following in vitro treatment of a
      CD52-positive human B cell line with CAMPATH-1H. Both the B and T CD52-negative
      cells were also found to be defective in surface expression of other GPI-anchored
      proteins. Biochemical analysis revealed a severe defect in the synthesis of a
      mature GPI precursor in both the B and T cell lines. Therefore the phenotype of
      these CD52-negative B and T cells closely resembles that of lymphocytes from
      patients with paroxysmal nocturnal haemoglobinuria (PNH), in which the first step
      of the GPI-biosynthetic pathway, i.e. synthesis of GlcNAc-phosphatidylinositol,
      is blocked. In all cases studied to date, this defect maps to a mutation of the
      phosphatidylinositolglycan class A (PIG-A) structural gene. We therefore
      amplified the PIG-A gene from both the GPI-negative B and T cells by PCR and
      determined the nucleotide sequence. No differences from the wild-type sequence
      were detected; therefore a classical PNH mutation cannot be responsible for the
      GPI-biosynthesis defect in these cell lines. Significantly, the GPI-negative
      phenotype of the B cells was reversible upon separation of the positive and
      negative cells, resulting in a redistribution to a mixed population with either
      CD52-positive or -negative cells, whereas populations of 100% CD52-negative T
      cells were stably maintained during culture. Therefore, whereas the GPI
      biosynthesis deficiency in the T cell lines may be due to a mutation in another
      gene required by the GPI-biosynthetic pathway, the reversible nature of this
      block in the B cell lines suggests a less direct cause, possibly an alteration in
      a regulatory factor. Overall, these data demonstrate that the PNH phenotype can
      be generated without a mutation in the PIG-A structural gene, and thereby
      identify a novel mechanism for the development of GPI deficiency.

PMID- 9148770
TI  - Identification of csk tyrosine phosphorylation sites and a tyrosine residue
      important for kinase domain structure.
AB  - The lack of a conserved tyrosine autophosphorylation site is a unique feature of
      the C-terminal Src-kinase, Csk, although this protein tyrosine kinase can be
      autophosphorylated on tyrosine residues in vitro and in bacteria. Here we show
      that human Csk is tyrosine phosphorylated in HeLa cells treated with sodium
      pervanadate. Phosphorylation in vivo occurs mainly at Tyr-184 and in vitro mainly
      at Tyr-304. A Y304F mutation strongly decreased Csk phosphorylation in vitro, and
      a Y184F mutation abolished tyrosine phosphorylation in vivo. A catalytically
      inactive form of Csk was also phosphorylated on Tyr-184 in vivo, suggesting that
      this is not a site of autophosphorylation. The kinase activity of the Y184F
      protein was not changed, while the Y304F protein showed one-third of wild-type
      activity. Three-dimensional modelling of the Csk kinase domain indicated that the
      Y304F mutation abolishes one of two conserved hydrogen bonds between the upper
      and the lower lobes in the open conformation of the kinase domain. Phosphopeptide
      binding studies suggested that phosphorylation of Tyr-184 creates a binding site
      for low-molecular-mass proteins. Cellular Csk was associated with several
      phosphoproteins, some of which were interacting with the Csk SH2 domain. Taken
      together these results indicate that Csk can be phosphorylated in vivo at Tyr-184
      by an as yet unknown tyrosine kinase, and that autophosphorylation of Tyr-304
      occurs only at abnormally high Csk concentrations in vitro. Furthermore, Tyr-304
      is required for the maintenance of the structure of the Csk kinase domain.

PMID- 9148772
TI  - The PLEES proteins: a family of structurally related enzymes widely distributed
      from bacteria to humans.

PMID- 9148771
TI  - Signal transduction through epidermal growth factor receptor is altered in HeLa
      monolayer cells during mitosis.
AB  - Epidermal growth factor (EGF)-induced signalling was studied separately in the
      mitosis and G2-phases of HeLa monolayer cells presynchronized (1) by amethopterin
      inhibition and thymidine release or (2) by nocodazole. For comparison, cells were
      treated with the phorbol ester phorbol 12-myristate 13-acetate (PMA). In contrast
      with the observed responses effected by PMA, which seem to be independent of cell
      cycle and synchronization conditions, those induced by EGF are greatly influenced
      by both criteria. Synchronization with nocodazole abolished the EGF-induced
      stimulation of phosphoinositide hydrolysis in G2 as well as in mitotic cells
      although tyrosine phosphorylation of the EGF receptor and phospholipase Cgamma1
      could be shown to occur, especially in G2 cells. Synchronization with
      amethopterin/thymidine showed that, in contrast with G2 cells, mitotic cells were
      not able to react to EGF with an increase in phosphoinositide hydrolysis although
      a certain degree of EGF receptor dimerization and autophosphorylation as well as
      tyrosine phosphorylation of phospholipase Cgamma1 could still be shown to occur
      in mitosis. The results seem to indicate that the EGF pathway leading to a
      stimulation of phosphoinositide hydrolysis is attenuated at different levels and
      requires a cytoskeletal condition that is not present either after treatment (24
      h) with nocodazole or during normal mitosis of a monolayer cell.

PMID- 9148773
TI  - Surface signaling: novel transcription initiation mechanism starting from the
      cell surface.
AB  - Transcription of the ferric citrate transport genes of Escherichia coli is
      induced by a novel mechanism. Ferric citrate, the inducer, does not have to enter
      the cytoplasm to initiate transcription. Interaction of ferric citrate with the
      outer membrane receptor protein FecA induces transcription of the fec transport
      gene operon consisting of the fecIRABCDE genes. A signal from FecA occupied with
      ferric citrate is transmitted across the outer membrane into the periplasm with
      the help of the electrochemical potential of the cytoplasmic membrane and the Ton
      system. The signal is then transduced across the cytoplasmic membrane by the FecR
      protein, which in turn activates the FecI sigma-factor that directs the RNA
      polymerase core-enzyme to the fec transport gene promoter. The promoter of the
      regulatory genes fecI and fecR is not controlled by ferric citrate but is
      regulated by iron via the Fur repressor. It is proposed that the information flux
      from the cell surface to the cytoplasm involves a series of conformational
      changes of the proteins FecA, FecR, and FecI in that order. The level of the
      regulatory proteins FecI and FecR is adjusted to the intracellular iron
      concentration and determines the degree of the response of the cell to ferric
      citrate in the medium. Ferric citrate induces transcription of the fec transport
      genes under iron-limiting conditions. A regulatory device similar to the ferric
      citrate transport system exists in Pseudomonas putida WCS358. The synthesis of
      the outer membrane receptor PupB, involved in the transport of the ferric
      pseudobactins BN7 and BN8, is induced by the ferric siderophores and requires
      PupB and two proteins homologous to FecI and FecR.

PMID- 9148774
TI  - Environmental and physiological factors affecting the succinate product ratio
      during carbohydrate fermentation by Actinobacillus sp. 130Z.
AB  - Actinobacillus sp. 130Z fermented glucose to the major products succinate,
      acetate, and formate. Ethanol was formed as a minor fermentation product. Under
      CO2-limiting conditions, less succinate and more ethanol were formed. The
      fermentation product ratio remained constant at pH values from 6.0 to 7.4. More
      succinate was produced when hydrogen was present in the gas phase. Actinobacillus
      sp. 130Z grew at the expense of fumarate and l-malate reduction, with hydrogen as
      an electron donor. Other substrates such as more-reduced carbohydrates (e.g., d
      sorbitol) resulted in higher succinate and/or ethanol production. Actinobacillus
      sp. 130Z contained the key enzymes involved in the Embden-Meyerhof-Parnas and the
      pentose-phosphate pathways and contained high levels of phosphoenolpyruvate (PEP)
      carboxykinase, malate dehydrogenase, fumarase, fumarate reductase, pyruvate
      kinase, pyruvate formate-lyase, phosphotransacetylase, acetate kinase, malic
      enzyme, and oxaloacetate decarboxylase. The levels of PEP carboxykinase, malate
      dehydrogenase, and fumarase were significantly higher in Actinobacillus sp. 130Z
      than in Escherichia coli K-12 and accounted for the differences in succinate
      production. Key enzymes in end product formation in Actinobacillus sp. 130Z were
      regulated by the energy substrates.

PMID- 9148777
TI  - Application of autolysin and deoxyribonuclease profiles generated by renaturing
      SDS-PAGE in the comparison of selected Proteobacteria.
AB  - SDS-PAGE of cell-free extracts in gels containing bacterial murein or DNA
      allowed, after enzyme renaturation and staining of nonhydrolysed substrate, the
      detection of multiple autolysin or deoxyribonuclease activities directly in the
      gel as zones of clearing. Enzyme profiles of Proteobacteria which are, or were at
      one time, classified in the genus Pseudomonas were compared. For each species, a
      relatively large number of autolysin and deoxyribonuclease activities were
      detected. The distribution, numbers and intensities of zones of clearing in the
      gel provided complex species-specific patterns. Extensive data from two
      fundamental, and presumably evolutionarily distinct classes of enzymes were thus
      generated for purposes of comparison. Neither analysis suggested that these
      bacteria could represent a single natural cluster of species, lending support to
      their present multigeneric status. Ethidium-bromide-stained gels could be
      subsequently stained with Coomassie blue. This allowed the mapping of many
      deoxyribonuclease activities to particular peptides in the cell-free extract. In
      addition, modification of the substrate or renaturation buffer enabled a
      preliminary characterisation of several deoxyribonucleases in terms of their
      stability, substrate specificity, and other parameters expected to affect enzyme
      activity. Individual deoxyribonucleases could be located and screened for desired
      properties without prior purification.

PMID- 9148780
TI  - Deletion of two downstream genes alters expression of the hmc operon of
      Desulfovibrio vulgaris subsp. vulgaris Hildenborough.
AB  - The hmc operon of Desulfovibrio vulgaris subsp. vulgaris Hildenborough consists
      of six genes (hmcA to hmcF) that encode structural components of the high
      molecular-mass cytochrome redox protein complex (the Hmc complex). Two genes
      (rrf1 and rrf2) encoding regulatory proteins are present downstream of hmcF.
      Expression of the hmc operon, monitored by incubating protein blots with HmcA
      specific or HmcF-specific antibodies, was found to be highest when hydrogen was
      the sole electron donor for sulfate reduction. Use of lactate or pyruvate as
      electron donor reduced expression of the hmc operon. A mutant with a deletion of
      the rrf1 and rrf2 genes was generated with the sacB mutagenesis method. This
      mutant overexpressed the hmc operon approximately threefold. It grew more rapidly
      than the wild type when hydrogen was used as the electron donor for sulfate
      reduction, but more slowly than the wild type when lactate was used. The results
      indicate that a physiological function of the Hmc complex is in electron flow
      from hydrogen to sulfate. At least one redox carrier is shared competitively by
      the hydrogen and lactate oxidation pathways in D. vulgaris.

PMID- 9148781
TI  - Enzymology of the degradation of (di)chlorobenzenes by Xanthobacter flavus 14p1.
AB  - Xanthobacter flavus 14p1 used 1,4-dichlorobenzene as the sole source of carbon
      and energy but did not grow on other (chloro)aromatic compounds. 1,4
      Dichlorobenzene was attacked by a chlorobenzene dioxygenase, and the intermediate
      chlorocatechol was metabolized by the modified ortho pathway. All enzymes
      necessary to convert 1, 4-dichlorobenzene to 3-oxoadipate showed a low substrate
      specificity and also accepted the respective intermediates of chlorobenzene or 1,
      3-dichlorobenzene degradation. Of the three compounds chlorobenzene, 1,4
      dichlorobenzene, and 1,3-dichlorobenzene, the latter was the most toxic for X.
      flavus 14p1. Furthermore, 1,3-dichlorobenzene did not induce chlorocatechol 1,2
      dioxygenase activity of the organism. Chlorobenzene, however, induced
      chlorocatechol 1,2-dioxygenase, dienelactone hydrolase, and maleylacetate
      reductase activities. As demonstrated by chloride release, also chlorobenzene
      dioxygenase, chlorobenzene cis-dihydrodiol dehydrogenase, and chloromuconate
      cycloisomerase activities were present in chlorobenzene-induced cells, but
      chlorobenzene failed to support growth. Presumably a toxic compound was formed
      from one of the intermediates.

PMID- 9148784
TI  - Diversity of alpha and beta subunits of T-cell receptors specific for the H4
      minor histocompatibility antigen.
AB  - The mouse H4 minor histocompatibility antigen (HA) includes a single H2Kb-bound
      peptide that stimulates rejection of skin allografts and generation of cytolytic
      T lymphocytes (CTL). We evaluated the diversity of the CTL response to this
      single minor HA peptide by sequencing alpha and beta chains of T-cell receptors
      (Tcr) from H4-specific CTLs as a first step toward understanding the diversity of
      Tcrs specific for single minor HA. We selected H4-specific CTL clones from short
      term lines that were restricted by Kb (19 clones), Kbm5 (7 clones), and Kbm11 (10
      clones). Whereas multiple V alpha and V beta family members were identified in
      the panel of Kb-restricted CTLs, five VB genes and one VA subfamily were
      predominant in CTLs derived from multiple individuals. Similar distributions were
      observed with Kbm5- and Kbm11-restricted CTLs, suggesting that these two mutants
      did not alter Tcr gene usage observable at the VA and/or VB gene levels.
      Negatively charged residues were present in the CDR3 regions of 12/13 unique Kb
      restricted beta chains. A comparable observation was made with Kbm5-restricted
      CTLs, and the distributions of these residues among CDR3 positions were similar
      in the two CTL panels. However, the Kbm11 mutation dramatically altered the
      distribution of these residues resulting in their presence in positions 10-12 of
      CDR3 regions in all CTLs. These results indicate that the Tcrs expressed by CTLs
      specific for this single minor HA peptide are oligoclonal and characterized by
      the presence of negatively charged residues in beta CDR3 regions, the
      distribution of which is profoundly altered by the Kbm11 mutation.

PMID- 9148785
TI  - Identification of immunogenic epitopes of GAD 65 presented by Ag7 in non-obese
      diabetic mice.
AB  - The autoantigen glutamic acid decarboxylase 65 (GAD 65) is believed to be an
      important target antigen in insulin-dependent diabetes mellitus (IDDM), since an
      age-related spontaneous breakdown in tolerance is observed, and cell-mediated and
      autoantibody immune responses have been reported in humans and NOD mice. We
      sought to identify immunogenic epitopes of GAD 65 which are presented to T cells
      by the type I diabetes susceptibility allele (Ag7), using overlapping 15-mer
      synthetic peptides spanning the entire sequence of this protein. Four epitopes
      (p206 - 220, p221 - 235, p286 - 300, p571 - 585) were identified by screening a
      panel of T-cell hybridomas generated from GAD 65-immunized NOD mice. These
      immunogenic epitopes are unrelated to the previously described T-cell epitopes of
      GAD 65 reported in NOD mice. Of the GAD 65 amino acid sequence, 206 - 220 and 221
      - 235 are the two most dominant T-cell epitopes identified in this study. Sixty
      three percent and 25% of GAD 65-responding T cell hybridomas react to p206 - 220
      and p221 - 235, respectively. The remaining two peptides (p286 - 300, p571 - 585)
      are less dominant T-cell responses. The identification of the whole spectrum of
      GAD 65 Ag7 epitopes should further the investigation of the role of this
      autoantigen in the pathogenesis of IDDM.

PMID- 9148786
TI  - The role of MHC class I heterodimer expression in mouse ankylosing enthesopathy.
AB  - Ankylosing enthesopathy (ANKENT) is a spontaneous mouse joint disease with
      strikingly similar pathology to human HLA-B27-associated enthesopathies such as
      ankylosing spondylitis. In C57Bl/10 mice, transgenic HLA-B*2702 as well as H2
      genes have been shown to be relative risk factors for ANKENT. To investigate the
      role of major histocompatibility complex (MHC) class I expression in disease
      pathogenesis, ANKENT occurrence was compared among beta2-microglobulin (beta2m)
      knockout littermates with or without transgenes for HLA-B*2702 and human beta2m.
      In the knockout phenotype lacking beta2m, ANKENT occurrence is significantly
      reduced (P = 0.016). In the absence of beta2m, B*2702 is not detected on the cell
      membrane, nor does it increase the risk for ANKENT. This means that the previous
      finding that HLA-B*2702 increases susceptibility to ANKENT in C57Bl/10 mice
      cannot be ascribed to a transgene insertion effect. Rather, in order to increase
      disease susceptibility, B*2702 must be coexpressed with mouse beta2m (mo-beta2m).
      In contrast, when HLA-B*2702 is expressed with beta2m of human origin, disease
      susceptibility is not affected. Thus, both H2(b)-derived class I heterodimers and
      HLA-B*2702/mo-beta2m heterodimers contribute to ANKENT susceptibility.

PMID- 9148787
TI  - Probing the stability of class I major histocompatibility complex (MHC) molecules
      on the surface of human cells.
AB  - We used binding of a fluorescent adduct of beta2-microglobulin, fluorescein
      beta2m, to probe the stability of class I HLA molecules on the surface of human
      cells. The weight of the literature suggests that this ligand binds to heavy
      chains that have lost beta2m and possibly peptide as well. Hence Fl-beta2m
      reports on the stability of the class I HLA trimer. A small fraction of HLA
      molecules, approximately 5%, binds Fl-beta2m on both resting and activated T
      cells. A larger fraction of all HLA molecules binds Fl-beta2m in FO-1 cells,
      beta2m-deficient cells, transfected with various B2m genes. HLA molecules of FO-1
      cells are more stable when expressed with human beta2m, than when expressed with
      mouse beta2m. The non-covalent association of HLA heavy chains, beta2m and
      peptide implies that eventually every molecule of HLA trimer ought to dissociate
      and bind Fl-beta2m. In fact, the extent of exchange is limited by the lifetime of
      a given molecule at the cell surface. beta2m exchange decreases as cell
      concentration increases, suggesting that some density-dependent process acts to
      enhance degradation or denaturation of beta2m-free HLA heavy chains.

PMID- 9148788
TI  - Partitioning of genetic variation between regulatory and coding gene segments:
      the predominance of software variation in genes encoding introvert proteins.
AB  - In considering genetic variation in eukaryotes, a fundamental distinction can be
      made between variation in regulatory (software) and coding (hardware) gene
      segments. For quantitative traits the bulk of variation, particularly that near
      the population mean, appears to reside in regulatory segments. The main
      exceptions to this rule concern proteins which handle extrinsic substances, here
      termed extrovert proteins. The immune system includes an unusually large
      proportion of this exceptional category, but even so its chief source of
      variation may well be polymorphism in regulatory gene segments. The main evidence
      for this view emerges from genome scanning for quantitative trait loci (QTL),
      which in the case of the immune system points to a major contribution of pro
      inflammatory cytokine genes. Further support comes from sequencing of major
      histocompatibility complex (Mhc) class II promoters, where a high level of
      polymorphism has been detected. These Mhc promoters appear to act, in part at
      least, by gating the back-signal from T cells into antigen-presenting cells. Both
      these forms of polymorphism are likely to be sustained by the need for
      flexibility in the immune response. Future work on promoter polymorphism is
      likely to benefit from the input from genome informatics.

PMID- 9148789
TI  - On naming H2 haplotypes: functional significance of MHC class Ib alleles.
AB  - George D. Snell began defining and naming the H2 haplotypes many years ago by
      histogenetic typing. Since then, a few haplotypes have been given an additional
      letter, such as bc for strain 129, to show that they are minor variants from the
      prototype (b). But by and large, differences in nonclassical class I antigens
      have been known (only?) to those in the field without being acknowledged by a
      separate haplotype symbol. Thus, strains BALB/c and NZB/BlNJ are both considered
      H2d and strains C3H/HeJ and B10.BR are both called H2k, although each pair
      differs in the TL and Qa1 antigens. In parallel with the interest in nonclassical
      class I antigens, the need for an appropriate haplotype nomenclature is growing.
      The haplotypes that require splitting are b, d, k, q, and s; the symbol bc should
      be retained and used, and, for the other haplotypes, the suffix 2 denotes a Qa1a
      haplotype with highly TL-positive thymocytes.

PMID- 9148790
TI  - Class I mhc genes of cichlid fishes: identification, expression, and
      polymorphism.
AB  - Cichlid fishes of the East African Rift Valley lakes constitute an important
      model of adaptive radiation. Explosive speciation in the Great Lakes, in some
      cases as recently as 12 400 years ago, generated large species flocks that have
      been the focus of evolutionary studies for some time. The studies have, however,
      been hampered by the paucity of biochemical markers for phylogenetic
      reconstruction. Here, we describe a set of markers which should help to alleviate
      this problem. They are the class I genes of the major histocompatibility complex.
      We provide evidence for the existence of at least 17 class I loci in cichlid
      fishes, and for extensive polymorphism of three of these loci. Since the
      polymorphism has a trans-species character, it will be possible to use it in
      investigating the founding events of the individual species. The sequences of the
      cichlid class I fishes support the monophyly of actinopterygian fish on the one
      hand, and of tetrapods on the other.

PMID- 9148791
TI  - The mystery of HLA-B27 and disease.

PMID- 9148793
TI  - Tropospheric air pollution: ozone, airborne toxics, polycyclic aromatic
      hydrocarbons, and particles.
AB  - Tropospheric air pollution has impacts on scales ranging from local to global.
      Reactive intermediates in the oxidation of mixtures of volatile organic compounds
      (VOCs) and oxides of nitrogen (NOx) play central roles: the hydroxyl radical
      (OH), during the day; the nitrate radical (NO3), at night; and ozone (O3), which
      contributes during the day and night. Halogen atoms can also play a role during
      the day. Here the implications of the complex VOC-NOx chemistry for O3 control
      are discussed. In addition, OH, NO3, and O3 are shown to play a central role in
      the formation and fate of airborne toxic chemicals, mutagenic polycyclic aromatic
      hydrocarbons, and fine particles.

PMID- 9148802
TI  - Disordered biopyriboles, amphibole, and talc in the Allende meteorite: products
      of nebular or parent body aqueous alteration?
AB  - Transmission electron microscope observations of the Allende carbonaceous
      chondrite provided evidence of widespread hydrous phases replacing enstatite in
      chondrules. Calcic amphibole and talc occur in thin (less than 0.3 micrometer)
      crosscutting veins and as alteration products of primary chondrule glass in
      contraction cracks within the enstatite. In addition, talc and disordered
      biopyriboles were found replacing enstatite grains along cracks and fractures.
      Although rare hydrous phases have been reported in calcium- and aluminum-rich
      inclusions in the Allende meteorite, these observations suggest that aqueous
      fluids played a much more significant role in the mineralogical and geochemical
      evolution of Allende than has previously been thought.

PMID- 9148804
TI  - Reversible unfolding of individual titin immunoglobulin domains by AFM.
AB  - Single-molecule atomic force microscopy (AFM) was used to investigate the
      mechanical properties of titin, the giant sarcomeric protein of striated muscle.
      Individual titin molecules were repeatedly stretched, and the applied force was
      recorded as a function of the elongation. At large extensions, the restoring
      force exhibited a sawtoothlike pattern, with a periodicity that varied between 25
      and 28 nanometers. Measurements of recombinant titin immunoglobulin segments of
      two different lengths exhibited the same pattern and allowed attribution of the
      discontinuities to the unfolding of individual immunoglobulin domains. The forces
      required to unfold individual domains ranged from 150 to 300 piconewtons and
      depended on the pulling speed. Upon relaxation, refolding of immunoglobulin
      domains was observed.

PMID- 9148805
TI  - Folding-unfolding transitions in single titin molecules characterized with laser
      tweezers.
AB  - Titin, a giant filamentous polypeptide, is believed to play a fundamental role in
      maintaining sarcomeric structural integrity and developing what is known as
      passive force in muscle. Measurements of the force required to stretch a single
      molecule revealed that titin behaves as a highly nonlinear entropic spring. The
      molecule unfolds in a high-force transition beginning at 20 to 30 piconewtons and
      refolds in a low-force transition at approximately 2.5 piconewtons. A fraction of
      the molecule (5 to 40 percent) remains permanently unfolded, behaving as a
      wormlike chain with a persistence length (a measure of the chain's bending
      rigidity) of 20 angstroms. Force hysteresis arises from a difference between the
      unfolding and refolding kinetics of the molecule relative to the stretch and
      release rates in the experiments, respectively. Scaling the molecular data up to
      sarcomeric dimensions reproduced many features of the passive force versus
      extension curve of muscle fibers.

PMID- 9148806
TI  - Inhibition of pathogenicity of the rice blast fungus by Saccharomyces cerevisiae
      alpha-factor.
AB  - Magnaporthe grisea is a fungal pathogen with two mating types, MAT1-1 and MAT1-2,
      that forms a specialized cell necessary for pathogenesis, the appressorium.
      Saccharomyces cerevisiae alpha-factor pheromone blocked appressorium formation in
      a mating type-specific manner and protected plants from infection by MAT1-2
      strains. Experiments with alpha-factor analogs suggest that the observed activity
      is due to a specific interaction of alpha-factor with an M. grisea receptor.
      Culture filtrates of a MAT1-1 strain contained an activity that inhibited
      appressorium formation of mating type MAT1-2 strains. These findings provide
      evidence that a pheromone response pathway exists in M. grisea that can be
      exploited for plant protection.

PMID- 9148807
TI  - Effectiveness of anthracycline against experimental prion disease in Syrian
      hamsters.
AB  - Prion diseases are transmissible neurodegenerative conditions characterized by
      the accumulation of protease-resistant forms of the prion protein (PrP), termed
      PrPres, in the brain. Insoluble PrPres tends to aggregate into amyloid fibrils.
      The anthracycline 4'-iodo-4'-deoxy-doxorubicin (IDX) binds to amyloid fibrils and
      induces amyloid resorption in patients with systemic amyloidosis. To test IDX in
      an experimental model of prion disease, Syrian hamsters were inoculated
      intracerebrally either with scrapie-infected brain homogenate or with infected
      homogenate coincubated with IDX. In IDX-treated hamsters, clinical signs of
      disease were delayed and survival time was prolonged. Neuropathological
      examination showed a parallel delay in the appearance of brain changes and in the
      accumulation of PrPres and PrP amyloid.

PMID- 9148808
TI  - A membrane network for nutrient import in red cells infected with the malaria
      parasite.
AB  - The human malaria parasite Plasmodium falciparum exports an interconnected
      network of tubovesicular membranes (the TVM) that extends from the parasite's
      vacuolar membrane to the periphery of the red cell. Here it is shown that
      extracellular solutes such as Lucifer yellow enter the TVM and are delivered to
      the parasite. Blocking the assembly of the network blocked the delivery of
      exogenous Lucifer yellow, nucleosides, and amino acids to the parasite without
      inhibiting secretion of plasmodial proteins. These data suggest that the TVM is a
      transport network that allows nutrients efficient access to the parasite and
      could be used to deliver antimalarial drugs directly into the parasite.

PMID- 9148809
TI  - Localization of Xenopus Vg1 mRNA by Vera protein and the endoplasmic reticulum.
AB  - In many organisms, pattern formation in the embryo develops from the polarized
      distributions of messenger RNAs (mRNAs) in the egg. In Xenopus, the mRNA encoding
      Vg1, a growth factor involved in mesoderm induction, is localized to the vegetal
      cortex of oocytes. A protein named Vera was shown to be involved in Vg1 mRNA
      localization. Vera cofractionates with endoplasmic reticulum (ER) membranes, and
      endogenous Vg1 mRNA is associated with a subcompartment of the ER. Vera may
      promote mRNA localization in Xenopus oocytes by mediating an interaction between
      the Vg1 3' untranslated region and the ER subcompartment.

PMID- 9148854
TI  - Effect of vitamin E and beta-carotene on DNA strand breakage induced by tobacco
      specific nitrosamines and stimulated human phagocytes.
AB  - The tobacco-specific nitrosamines (TSNAs), nitrosonornicotine (NNN) and 4-(N
      methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are metabolites of nicotine
      and are major carcinogens in cigarette smoke. Chronic inflammation may promote
      the carcinogenic effect of these nitrosamines through the generation of oxygen
      radicals. To evaluate the effect of oxygen radicals on TSNA-induced genetic
      damage, cultured human lung cells treated with NNN or NNK were exposed to
      stimulated human phagocytes and assayed for single-strand DNA breaks. TSNAs or
      stimulated phagocytes alone cause a significant increase in strand breakage which
      is augmented in an additive fashion when the two are combined. Pretreating the
      cells with vitamin E or beta carotene provided significant protection against the
      induction of DNA damage but vitamin E was significantly more effective than beta
      carotene. These data suggest a possible approach to the chemoprevention of
      tobacco-induced carcinogenesis.

PMID- 9148853
TI  - BCL-2: the pendulum of the cell fate.
AB  - The homeostasis of normal tissues is a balance between cell proliferation and
      cell death. Alterations of both pathways contribute to a clonal expansion of
      cancer cells. Bcl-2 and its family play an important role in the regulation of
      the apoptotic pathway. Apoptosis or programmed cell death is an active form of
      cell suicide that is characterized by specific morphological and biochemical
      events. These include cleavege of genomic DNA into oligonucleosome-length DNA
      fragments by endonucleases, chromatin condensation and marginalization, nuclear
      fragmentation, plasma membrane blebbing, and cell shrinkage. Though the role of
      apoptosis is clearly defined in the maintaining of physiological tissue
      homeostasis, several pathological conditions and external factors cause
      apoptosis. Anticancer drugs and radiation, two of the most important tools in the
      cancer treatment, cause apoptotic cell death. The understanding of the mechanisms
      underlying the regulation of the apoptosis in response to different types of DNA
      damage might provide relevant information to improve cancer treatment. In this
      review we mainly discuss bcl-2 and its partners in human cancers and how their
      disregulation might contribute to the development and the difficult treatment of
      cancer.

PMID- 9148855
TI  - Dacarbazine-induced immunogenicity of a murine leukemia is attenuated in cells
      transfected with mutated K-ras gene.
AB  - Strong immunogenicity is induced by antitumor triazene compounds in tumor cells
      through a mutagenic mechanism. A highly immunogenic <<D>> clone, isolated from a
      dacarbazine-treated L5178Y leukemia of DBA/2 mice, was transfected with K-ras
      mutated at codon 12 (i.e. ras(m12)). This transfected clone presents at least 2
      mutations, one concerning K-ras gene, and the other affecting an unrelated gene,
      responsible for the generation of a highly immunogenic, MHC class I restricted
      non-self peptide. The results indicate that cells of <<D>> clone transfected with
      ras(m12) were less immunogenic than cells of the same origin transfected with the
      vector alone. Moreover, ras(m12)-transfected cells showed lower levels of H-2K(d)
      gene expression with respect to those detectable in control cells. In addition,
      in vivo and in vitro sensitization against <<D>> clone carrying mutated ras did
      not result in a strong cytotoxic T lymphocyte response against ras(m12)
      transfected non immunogenic L5178y target cells. These preliminary results
      suggest that K-ras mutation could down-regulate the level of tumor
      immunogenicity, possibly acquired through a mutagenic process affecting other
      unrelated genes.

PMID- 9148856
TI  - Effect of epirubicin on 3H-thymidine labelling index in cultured L-strain cells.
AB  - The effect of epirubicin (EPI) on 3H-thymidine labelling index (3H-TdR LI) of L
      strain cells in culture was investigated. EPI concentrations of 0.001 microg/ml,
      0.01 microg/ml and 0.1 microg/ml were applied to the cells for 4, 8, 16 and 32
      hours. Following the treatment with EPI, labelling process in 3H-TdR medium
      continued for 0, 2, 4, 8, 16, 20, 22, 25 and 30 hours. The results showed that
      EPI diminished labelling index of L-strain cells depends on time and applied
      concentrations. When compared to control this decrease was found statistically
      significant (p<0.001) in each group.

PMID- 9148857
TI  - Induction of the multidrug-transporter P-glycoprotein by 3'-azido-3'
      deoxythymidine (AZT) treatment in tumor cell lines.
AB  - A major form of multidrug resistance, which represents a serious obstacle to the
      success of chemotherapy, is caused by the over-expression of MDR-1 gene encoded P
      glycoprotein. The present investigation was aimed to determine whether AZT, a
      cytostatic agent that interferes with the human immunodeficiency virus
      replication, is able to induce MDR-1 expression in tumor cells. After a short
      term exposure of human lymphoblastoid cells to AZT MDR-1 P-glycoprotein was found
      in the treated cells. This ATP-dependent drug-efflux pump interferred with
      cytotoxic efficacy of anticancer drugs such as vinblastine. This phenomenon
      should be carefully considered during anti-viral and anti-tumoral combined
      chemotherapies in AIDS patients.

PMID- 9148859
TI  - Effects of ethane-1-hydroxy-1, 1 diphosphonate on Dunn osteosarcoma cells.
AB  - We investigated the effects of ethane-1-hydroxy-1, 1 diphosphonate (EHDP) on Dunn
      osteosarcoma cells in vivo and in vitro. In in vivo study, an increase of tumor
      volume was significantly suppressed in the EHDP administered groups compared with
      the control group. Histologically, Dunn osteosarcoma cells' viability was
      maintained after EHDP administration. However, fatty degeneration of tumor tissue
      was suspected in two of eight mice in the 5.0 mg/kg EHDP administered group. In
      vitro study, EHDP inhibited DNA synthesis and induced morphological changes, such
      as pycnotic cells. These findings show that the growth of Dunn osteosarcoma cells
      is inhibited by EHDP.

PMID- 9148858
TI  - Anticarcinogenic action of apple pectin on fecal enzyme activities and mucosal or
      portal prostaglandin E2 levels in experimental rat colon carcinogenesis.
AB  - Pectin is a partially methoxylated polymer of galacturonic acid obtained from
      fruits. Among pectin, apple pectin exerts stronger bacteriostatical action on
      Staphylococcus aureus, Streptococcus faecalis, Pseudomonas aeruginosa and
      Escherichia coli in comparison with citrus pectin. In this study, we used water
      soluble methoxylated pectin from apple. The diet, supplemented by 20% apple
      pectin, significantly decreased the number of tumors and the incidence of colon
      tumor. PGE2 level in distal colonic mucosa in 20% apple pectin fed rats were
      lower than those in basal diet fed rats. Fecal beta-glucuronidase activities in
      the apple pectin fed group, which has been considered a key enzyme for the final
      activation of Dimethylhydrazine metabolism to carcinogens in the colonic lumen,
      were signifieantly lower than those in control group at initiation stage of
      carcinogenesis. In the case the concentrations of beta-glueosidase and
      azoreductase were also decreased. The effect of apple pectin on the colon
      carcinogenesis may partially depend on PGE, concentration decrease in colonic
      mucosa and on the type of pectin, also related to fecal enzyme activities.

PMID- 9148860
TI  - Adult genitourinary sarcomas: a report of seventeen cases and review of the
      literature.
AB  - Seventeen adult urologic sarcomas treated at the Oncology Hospital of Ankara in
      the last ten-year period are described. There were six cases of paratesticular
      rhabdomyosarcoma (RMS), four cases of liposarcoma (LS), three cases of
      leiomyosarcoma (LMS); two cases of Kaposi sarcoma limited to glans penis, and
      only one primary malignant fibrous histiocytoma of the kidney. We report our ten
      years' experience with adult genitourinary sarcomas. The necessity for a uniform
      staging system and adequate multidisciplinary therapy are discussed.

PMID- 9148861
TI  - Molecular genetic analysis of TGF-beta1 in ovarian neoplasia.
AB  - Malignant ovarian tumours have been associated with a loss of autocrine growth
      inhibition by transforming growth factor-beta. This study aimed to detect
      abnormalities in the gene structure, expression and localization of TGF-beta1, in
      paraffin-embedded samples from 31 ovarian neoplasias (21 malignant, 5 borderline
      and 5 benign). Gene mutations in the region coding for the active protein were
      detected by PCR-SSCP analysis of exons 5, 6 and 7. mRNA expression and
      localization was studied by nonisotopic in situ hybridization (NISH) using cDNA
      probes generated by the reverse transcriptase polymerase chain reaction (RT-PCR),
      and immunohistochemistry, using antibodies against both intracellular and
      extracellular (matrix-associated) forms of TGF-beta1. Four mutations were found:
      one in exon 6 (serous adenocarcinoma), one in exon 7 (Mullerian tumor), and two
      in exons 5 and 6 from a serous cystoadenoma. TGF-beta1 mRNA was expressed in 87%
      and proteins in 90% of ovarian tumours. Most tumours expressing large amounts of
      TGF-beta1 mRNA, also contained a large number of protein binding sites. In
      malignant tumors, TGF beta1 was more strongly expressed in high-grade ovarian
      carcinomas with a cystic-papillary pattern than in tumours with a solid growth
      pattern. Normal ovarian tissue (follicles, granulosa cells) adjacent to tumor
      showed weak epithelial labeling and staining. Gene mutation did not correlate
      with histological type of tumor, mRNA or protein expression. TGF-beta1 mutation
      and abnormalities in its expression seem to occur in benign and malignant ovarian
      tumors, and could be involved in their pathogenesis. TGF beta1 gene mutations may
      act in multistage ovarian neoplasia, by reducing epithelial cell responsiveness
      to TGF-beta1 negative growth control.

PMID- 9148862
TI  - Molecular genetic analysis of TGF beta1 in breast cancer.
AB  - Conflicting data suggest that TGF-beta1 can either inhibit or promote the
      progression of breast cancer. To determine the biological role of TGF beta1 in
      mammary carcinoma, in this study we examined the gene structure, expression and
      localization of TGF-beta1 using paraffin-embedded samples from 32 (27 IDC, 1 ILC,
      1 DCIS, 1 ADH) breast lesions. Gene mutations in the region coding for the active
      protein were investigated by PCR-SSCP of exons 5, 6, and 7. mRNA -TGF-beta1
      expression and distribution was examined by NISH using cDNA probes generated by
      RT-PCR and immunohistochemistry. We detected two mutations in exon 6 TGF-beta1
      from IDC; and TGF beta1 mRNA and proteins in 28 (87%) of the tumors. Invasive
      breast carcinomas had more intense TGF-beta1 activity than CIS and than normal
      tissue adjacent to tumor. TGF beta1 mRNA and proteins were higher at the edge of
      the tumor than in the center and were also higher in less differentiated breast
      neoplasms. TGF-beta1 mRNA transcription and protein levels did not correlate
      either with TGF-beta1 exon 6 mutation or type and grade of differentiation of
      breast tumors. These observations suggest that TGF beta1 mutations in breast
      neoplasms might cause loss or inactivation of the growth inhibitory effects of
      TGF-beta1. They also support the proposed role of TGF-beta1 in the pathogenesis
      of breast cancer.

PMID- 9148863
TI  - Glycoprotein electrophoretic pattern in sera of patients with oral precancerous
      conditions and upper aerodigestive tract cancer.
AB  - Cancer of the upper aerodigestive tract is one of the leading sites of human
      malignancies in India. Various glycoproteins have been claimed to be specifically
      associated with cancer. Serum glycoprotein electrophoresis was carried out in
      sera obtained from 23 healthy individuals [10 without habit of tobacco
      consumption (NHT) 13 with habit of tobacco consumption (WHT)], 46 patients with
      oral precancerous conditions (OPC) and 110 untreated patients with upper
      aerodigestive tract cancer. Eighty-six samples from the cancer patients were also
      collected after initiation of anticancer therapy. The albumin, alpha, beta and
      gamma region glycoproteins were quantitated by densitometric scanning after
      separation by polyacrylamide disc gel (PADG) electrophoresis. Mean values of
      albumin and alpha region glycoproteins were significantly lower in WHT and
      patients with OPC as compared to NHT. The gamma region glycoproteins were
      significantly elevated in WHT, patients with OPC and untreated cancer patients as
      compared to the NHT. The albumin region glycoproteins were significantly low,
      whereas, gamma region glycoproteins were significantly elevated in nonresponders
      as compared to their pretreatment levels. The glycoprotein values in complete
      responders were comparable with NHT. An extra glycoprotein band was found in the
      post beta region, in most of the individuals (>50%) with habit of tobacco
      consumption in all the groups. There was a decrease in the albumin/gamma,
      alpha/gamma and beta/gamma values in patients with OPC as well as untreated
      cancer patients as compared to NHT. Albumin/gamma, alpha/gamma and beta/gamma
      values were lower in nonresponders as compared to their pretreatment value. The
      results indicate that the alterations in glycoprotein electrophoresis pattern may
      be useful for early detection of cancer of the upper aerodigestive tract. It may
      also be helpful in treatment monitoring of cancer patients.

PMID- 9148864
TI  - Ovarian cancer and unilateral naevoid telangiectasia: a rare association.
AB  - The Authors describe the case of a 58-year-old woman affected by erythematous
      telangiectasis lesions on the antero-lateral surface of the right hip during
      papillary serous cystoadenocarcinoma of the right ovary. The diagnosis, based on
      clinical and histological findings, was unilateral naevoid telangiectasia. After
      a review of literature the Authors assume a possible role of the oestrogens in
      the pathogenesis of such infrequent disease.

PMID- 9148865
TI  - Diagnosis of primary liver cancer using lectin affinity chromatography of serum
      alkaline phosphatase.
AB  - Serum alkaline phosphatase (sALP) can be separated into unbound liver type (L
      ALP) and bound bone type (B-ALP) by means of WGA affinity chromatography. The L
      ALP from the sera of normal adults and various liver diseases was found to show
      different chromatographic behaviours on DSA affinity column with multiple peaks
      of ALP activity after the L-ALP was treated with neuraminidase to remove the
      terminal sialic acids on the sugar chain of L-ALP. The L-ALP from normal sera
      contained no bound activity on DSA, whereas that from acute or chronic hepatisis,
      liver cirrhosis and biliary obstruction had a significant amount of bound
      fractions with weak and intermediate affinity. The strongly bound fraction(s) was
      only present in the L-ALP serum from primary liver cancer (PLC) and the positive
      rate of its appearance was 100% in 38 cases of PLC, including 8 alpha-fetoprotein
      (AFP) negative cases. The WGA chromatography can be skipped and similar results
      are obtained. The percentage of the strongly bound fraction in serum L-ALP was
      not related to the level of either sALP activity or AFP, and the appearance of
      the strongly bound fraction is attributed to the structural difference of sugar
      chains in L-ALP. Therefore, this L-ALP fraction may be assumed as a new index in
      the diagnosis of PLC, and the different profiles of sALP or L-ALP on DSA
      chromatography may be used in the differential diagnosis of benign and malignant
      liver diseases.

PMID- 9148866
TI  - Primary anorectal melanomas: an istitutional experience.
AB  - Primary melanomas (M) of the rectum and anal canal are a rare pathological event,
      constituting approximately 1% of all invasive tumors in this site. From January
      1973 to December 1990 at the Istituto Nazionale per lo Studio e 1a Cura dei
      Tumori of Milan, 11 patients were treated for M (5 males and 6 females), with a
      mean age of 60 years (range 40-80). The site of origin of the M was rectal in
      four patients, anal in five patients and in the anorectal joint in two patients.
      The lesion was prevalently polypoid and the average size was 4 cm (1-7.5 cm).
      Symptoms referred by the patients were rectal bleeding and tenesmus. In one
      patient the diagnosis was made after biopsy of an inguinal metastatic lymphnode.
      Of the 11 patients, six underwent curative resection (four Miles' resections and
      two local excisions). One patient is still alive with no evidence of disease
      after 120 months. The remaining five patients were submitted to palliative
      treatment, due to the presence of metastases in four of them and to age and
      general conditions in one. All of these patients died at 1, 2, 4, 5, and 6 months
      (median: 4 months). Overall median survival was eight months: 20 months in the
      radically treated group and four months in the palliatively treated group. Our
      data are in agreement with those reported in literature and confirm the
      prognostic severity of anorectal M due both to late diagnosis and the biological
      aggressiveness of the neoplasm.

PMID- 9148867
TI  - Multicentre experience with combined hyperthermia and radiation therapy in the
      treatment of superficially located non-Hodgkin's lymphomas.
AB  - The combination of Radiation Therapy (RT) and Hyperthermia (HT) has proved to be
      an effective treatment for a wide variety of superficially located recurrences of
      different tumors, particularly those arising in previously irradiated areas. Few
      studies on the use of HT in the management of lymphomatous diseases have so far
      obtained interesting results. Eight patients with Non Hodgkin Lymphomas (LNH) - 4
      with cutaneous lymphomas and 4 with nodal recurrences after RT-Chemotherapy (CHT)
      treatment treated in three different Italian institutions with combined RT and HT
      are here reported. Rt dose ranged from 15 to 40 Gy with different fractionations,
      on the basis of previously received treatment. Hyperthermia was delivered using
      432 or 915 MHz external microwave applicators, according to extension and depth
      of the lesions and available equipment. All patients tolerated well the HT
      treatment, and in all cases average intratumoral temperatures were >42 degrees,
      with 3 out of 10 treated sites achieving the goal of average temperatures >42.5%.
      One patient, with recurrent NHL, is disease-free after 24 months from completion
      of combined therapy. Our results seem to confirm previous experiences, suggesting
      a role of HT/RT not only for palliative purposes in cutaneous lymphomas, but also
      as an adjunct to radiotherapy alone in selected patients with superficially
      located recurrences.

PMID- 9148868
TI  - Intensified carboplatin regimen with GM-CSF support in non-small cell lung cancer
      (NSCLC). A Hellenic Co-operative Oncology Group Study (HeCOG).
AB  - This is a continuation of a HeCOG previous trial utilizing carboplatin and
      vindesine in conventional doses as a non-toxic regimen provided easily on an
      outpatient basis in NSCLC. In the present study we investigated whether an
      intensified dose-carboplatin could yield a better response. Carboplatin at a dose
      of 450 mg/m2 dose in combination with vindesine 3 mg/m2 every three weeks and GM
      CSF support was used in a phase II study to treat 44 patients with non-small cell
      lung cancer (NSCLC). As compared to our previous study carboplatin dose intensity
      was increased from 75 mg/m2/wk to 150 mg/m2/wk. Six patients (13.6%) responded to
      treatment and all were partial responders. The median duration of response was 5
      months (range 1.5-9 month). After a retrospective analysis a dose response effect
      was not evident at different carboplatin AUC doses. Twenty patients (45.45%)
      experienced thrombocytopenia and seventeen patients (38.6%) anemia as major
      toxicities. This study shows that in NSCLC a dose-response effect does not exist
      between carboplatin dose intensification and response rate cannot be traced.

PMID- 9148869
TI  - Steroid hormone receptors and antineoplastic chemotherapy in human breast cancer.
AB  - Several clinical and experimental investigations suggest that the action of
      antineoplastic chemotherapy in premenopausal women influences the menopause. Such
      hormonal reactions are mediated via specific steroid hormone receptors.
      Therefore, connections between hormone receptors and antineoplastic chemotherapy
      can be assumed making possible to predict success of chemotherapy on the basis of
      receptor status. Nevertheless, clinical experiences and animal and cell culture
      experiments yielded controversial results. This was related to the predictive
      value of receptor status as well as to the benefits of combined hormone and
      chemotherapy treatments in concurrent or sequential form. It is undeniable that a
      displacing of steroidal ligand from its receptors by the usual antineoplastic
      drugs does not occur. Furthermore, the receptor levels remain unchanged after a
      treatment with antineoplastic drugs. Thus, the mechanism of action of
      chemotherapeutic drugs is not related directly to the presence or absence of
      steroid hormone receptors. Despite this fact the receptor status in
      chemotherapeutic regimes seems to be helpful to define low or high risk patients.
      Influences on the ER de-novo-synthesis, actions related to parameters
      representing reduced tumor growth rates, down-regulation of the receptor gene
      expression or via receptor mediated hormonal actions to other genes, like the
      apoptosis-related gene bcl-2, are thought to be possible mechanisms of action of
      antineoplastic drugs on steroid hormone receptors. Future investigations should
      monitor the ratios between exon lacking receptor variants and the wild-type
      receptor during chemotherapy or the control of a ligand uptake during
      chemotherapy by means of the positron emission tomography.

PMID- 9148870
TI  - Clinical use of the bcr/abl probe test in the evaluation of chronic myeloid
      leukemia patients.
AB  - CML is characterized by a reciprocal translocation between the abl and bcr genes
      on chromosomes 9 and 22 and is usually diagnosed by the presence of the
      Philadelphia (Ph1) chromosome.However, the translocation may also occur without
      the appearance of the Ph1 chromosome. In this study the diagnostic efficiency of
      the molecular hybridization assay was investigated in 227 patients using a probe
      specific for the bcr region of the gene. Gene rearrangements were observed in 96%
      of Ph1-positive cases and in 92% of the patients in whom no Ph1 chromosome could
      be detected by karyotype analysis. By using peripheral blood the assay is easy to
      perform and superior in sensitivity. Thus, it is recommended that this assay
      should be routinely used as anadjunct to classical cytogenetics.

PMID- 9148871
TI  - Depressive mood disorders in patients with operable breast cancer.
AB  - We studied 149 subjects admitted to hospital with operable, untreated breast
      cancer (108) or benign (41) breast disease (control group). Depression was
      evaluated before diagnosis and surgery, using MMPI and Rorschach tests, HDRS
      scale, and DSM-III-R diagnostic criteria during a semistructured interview. 62%
      of patients and 34% of controls (p<0.005) presented some depressive symptoms,
      whereas only 55% of patients and 18% of controls (p<0.001) met criteria for
      depressive mood disorders: 2% of patients and 0% of controls for major
      depression, 13% and 5% for dysthymia (p<0.05), 40% and 13% for depressive
      disorders NOS (p<0.001). No correlation was observed with respect to stage of
      disease, histopathologic grade, age and menopause except for ER status (p=0.03).
      During interview, 89% of patients and 65% of controls reported severe stressful
      life events 5+/-4 years before the clinical onset of the breast node. No
      differences were observed in the depression rating scales mean value whereas
      patients resulted more inhibited in their affection and emotionally controlled
      (Rorschach data) compared to controls (p<0.05). In conclusion, although the
      depression diagnostic criteria used may not be strictly correlated higher
      prevalence of depressive mood disorders and stressful life events were observed
      in patients in the pre-clinical phase of operable breast cancer. This may suggest
      an involvement of depression in the natural history of breast cancer.

PMID- 9148872
TI  - The role of somatostatin analogues in complete antiandrogen treatment in patients
      with prostatic carcinoma.
AB  - Somatostatin analogues (SMS-A) have been found to inhibit the growth of
      experimental tumors, as of prostate cancer, via several mechanisms as
      antihormonal and direct antimitogenic actions. It was demonstrated also that
      several SMS-A induce greater prostatic tumor regression with more pronounced
      histological changes if combined with LHRH analogues or in association with
      complete androgen blockade (CAB). In a phase II clinical trial we administered,
      in addition to CAB, SMS-A octreotide in 14 patients with stage D2 (group B)
      prostate cancer-8 previously hormonally treated (PHT) and 6 without any previous
      hormone treatment (NPHT); 4 other patients, 3 NPHT and one PHT, were treated with
      CAB only (group A). Antiandrogen and antitumoral activity followed assaying a)
      plasma testosterone b) prostatic specific antigen (PSA) c) prostatic acid
      phosphatase (PAP) levels and d) objective (o) and subjective (s) clinical
      improvement according to WHO criteria. Somatostatin activity was evaluated
      assaying Insulin like Growth Factor-1 (IGF-1) and Epidermal Growth Factor (EGF).
      In group B we observed 3 responses, with the best quality of response (oPR/sCR)
      among the 6 NPHT-patients (50%) and 3 responses among the PHT-patients (37,5%),
      two of them with an incomplete PHT. In group A, 2 out of 3 NPHT-patients had a
      response (oPR/sPR). Among group B patients we observed long symptom-free
      survival, when they responded (17 months), in comparison to group A patients (12
      months), but almost the same total duration of survival in the two groups, 18.5
      and 18 months, respectively. EGF and IGF-1 serum levels showed a distinct drop
      parallel to the decrease of PSA serum levels, among the patients with response
      vs. nonrespondent patients of group B during the treatment. Although our results
      showed that octreotide in small doses, in addition to CAB, having mild toxicity,
      enhance number, quality and perhaps the duration of symptom-free responses in
      patients with stage 2 prostate cancer, the therapeutic efficacy of this combined
      treatment remains to be ascertained in wider and better randomized clinical
      trials.

PMID- 9148873
TI  - Robots for surgeons or surgeons for robots?

PMID- 9148874
TI  - Image guided excision of a ruptured feeding artery "pedicle aneurysm" associated
      with an arteriovenous malformation in a child: case report.
AB  - Excision of a ruptured aneurysm located at a lenticulostriate feeding artery
      associated with an arteriovenous malformation was performed using image guided
      neuronavigation in an 8-year-old child. The management of this lesion, which is
      rare in childhood, demonstrates the potential of combining frameless stereotaxy
      for precise target approach with conventional open microneurosurgery to minimize
      morbidity. Because of the unavoidable shifting of the brain that occurs during
      surgery, a catheter pointing towards the dome of the aneurysm was placed using
      image guidance prior to insertion of spatulae.

PMID- 9148875
TI  - Three-dimensional magnetic resonance angiography in the planning of aneurysm
      surgery.
AB  - Standard planning for intracranial aneurysm surgery relies on the surgeon's
      intellectual reconstruction of the three-dimensional (3D) surgical field on the
      basis of a two-dimensional (2D) imaging modality, biplanar cerebral angiography.
      This method is relatively imprecise, and it relies on previous experience for
      optimal results. We describe a stereotactic magnetic resonance angiographic (MRA)
      guided method based on computer segmentation techniques for the planning of
      aneurysm surgery that has the potential of bringing a 3D perspective to the
      lesion. The method has been evaluated retrospectively on 20 surgical patients in
      whom the aneurysm orientation and relationship to parent vessels were shown to
      match presurgical 3D stereotactic display. When it is adapted to frameless
      interactive surgical navigation, this method may become a useful adjunct in the
      surgical obliteration of these life-threatening lesions.

PMID- 9148876
TI  - Comparison of laparoscopic imaging systems and conditions using a knot-tying
      task.
AB  - Pilot experiments to determine the important factors in the engineering of
      laparoscopic (videoscopic) imaging systems are described in this paper. In the
      first set of experiments, three videoscopic systems were compared by using a knot
      tying task: monoscopic, monoscopic with digital contrast enhancement, and
      stereoscopic. Direct viewing was used as a control. In both experienced and
      novice subject groups, no difference was found in completion time or errors
      between the videoscopic conditions. Performance with direct viewing was
      significantly better, however, indicating that there are factors in videoscopic
      imaging that degrade perception or distort the relationship between vision and
      motor response. In the second set of experiments, the effects of contrast and
      spatial resolution were examined by varying working distance and camera exposure
      while experienced subjects tied knots on high- and low-contrast surfaces. Good
      contrast was found to be most important at longer working distances. This result
      shows that performance of knot tying, a complex task, is affected by contrast
      sensitivity, which is a fundamental property of human vision.

PMID- 9148877
TI  - Image-interactive orientation in the middle cranial fossa approach to the
      internal auditory canal: an experimental study.
AB  - Approaches through the middle cranial fossa directed at reaching the internal
      auditory canal (IAC) invariably employ exposure of the geniculate ganglion, the
      superior semicircular canal (SSC) or the epitympanum. This involves risk to the
      facial nerve and hearing apparatus. To minimize this risk, we conducted a
      laboratory study on 9 cadaver temporal bones by using an image-interactive
      guidance system (StealthStation) to provide topographic orientation in the middle
      fossa approach. Surface anatomic fiducials such as the umbo of the tympanic
      membrane, Henle's spine, the root of the zygoma and various sutures were used as
      fiducials for registration of CT-images of the temporal bone. Accurate
      localization of the IAC was achieved in every specimen. Mean target localization
      error varied from 1.20 to 1.38 mm for critical structures in the temporal bone
      such as the apex of the cochlea, crus commune, ampula of the SSC and facial
      hiatus. Our results suggest that frameless stereotaxy may be used as an
      alternative to current methods in localizing the IAC in patients with small
      vestibular schwannomas or intractable vertigo undergoing middle fossa surgery.

PMID- 9148878
TI  - Multiple brain atlas database and atlas-based neuroimaging system.
AB  - For the purpose of developing multiple, complementary, fully labeled electronic
      brain atlases and an atlas-based neuroimaging system for analysis,
      quantification, and real-time manipulation of cerebral structures in two and
      three dimensions, we have digitized, enhanced, segmented, and labeled the
      following print brain atlases: Co-Planar Stereotaxic Atlas of the Human Brain by
      Talairach and Tournoux, Atlas for Stereotaxy of the Human Brain by Schaltenbrand
      and Wahren, Referentially Oriented Cerebral MRI Anatomy by Talairach and
      Tournoux, and Atlas of the Cerebral Sulci by Ono, Kubik, and Abernathey. Three
      dimensional extensions of these atlases have been developed as well. All two- and
      three-dimensional atlases are mutually preregistered and may be interactively
      registered with an actual patient's data. An atlas-based neuroimaging system has
      been developed that provides support for reformatting, registration,
      visualization, navigation, image processing, and quantification of clinical data.
      The anatomical index contains about 1,000 structures and over 400 sulcal
      patterns. Several new applications of the brain atlas database also have been
      developed, supported by various technologies such as virtual reality, the
      Internet, and electronic publishing. Fusion of information from multiple atlases
      assists the user in comprehensively understanding brain structures and
      identifying and quantifying anatomical regions in clinical data. The multiple
      brain atlas database and atlas-based neuroimaging system have substantial
      potential impact in stereotactic neurosurgery and radiotherapy by assisting in
      visualization and real-time manipulation in three dimensions of anatomical
      structures, in quantitative neuroradiology by allowing interactive analysis of
      clinical data, in three-dimensional neuroeducation, and in brain function
      studies.

PMID- 9148881
TI  - Memory, repression, and child sexual abuse: forensic implications for the mental
      health professional.
AB  - Childhood sexual abuse is prevalent in our society today. Over the last 30 years,
      mental health professionals have become increasingly involved in the assessment
      and treatment of adults who were sexually abused as children. The emergence of
      the phenomenon of recovered memories has divided both families and mental health
      professionals. The current debate over repressed memory as well as the prominent
      theories in this area are discussed. Recent legal developments of repressed
      memory litigation are discussed along with examples of legal cases that are most
      relevant to mental health professionals today.

PMID- 9148879
TI  - Interpreting the effectiveness of involuntary outpatient commitment: a conceptual
      model.
AB  - Many experimental trials of community mental health interventions fail to develop
      testable conceptual models of the specific mechanisms and pathways by which
      relevant outcomes may occur, thus falling short of usefully interpreting what
      happens inside the experimental "black box." This paper describes a conceptual
      model of involuntary outpatient commitment (OPC) for persons with severe and
      persistent mental disorders. The model represents an attempt to "unpack" the
      effects of OPC by incorporating several interacting variables at various stages.
      According to this model, court-mandated outpatient treatment may improve long
      term outcomes both directly and indirectly in several ways: by stimulating case
      management efforts, mobilizing supportive resources, improving individual
      compliance with treatment in the community, reducing clients' psychiatric
      symptoms and dangerous behavior, improving clients' social functioning, and
      finally by reducing the chance of illness relapse and rehospitalization. A
      randomized clinical trial of OPC is underway in North Carolina that will test the
      direct and indirect effects suggested by this model, using longitudinal data from
      the multiple perspectives of mental health clients, family members, and case
      managers.

PMID- 9148880
TI  - Toward the development of guidelines for the conduct of forensic psychiatric
      examinations.
AB  - Guidelines for conducting forensic psychiatric consultations and evaluations have
      not been clearly established. The authors offer and discuss such guidelines,
      which are based upon the boundary guidelines in general psychiatric practice,
      ethics principles in general psychiatry, ethics principles in forensic
      psychiatry, and the relevant case and statutory law. These guidelines are
      intended to assist the psychiatrist in appropriately conducting forensic
      evaluations whether in litigation or administrative proceedings.

PMID- 9148882
TI  - Survivors of sexual abuse allege therapist negligence.
AB  - In two recent litigation cases, adult survivors of sexual abuse claimed that
      their current symptomology was linked to the failure of mental health
      professionals to provide appropriate treatment. If mental health practitioners
      are to be held accountable for providing acceptable standards of treatment, these
      standards must be based on empirical evidence of the efficacy of treatment
      methodologies. This article provides a review of the professional literature and
      determines that with the exception of time-limited group treatment, which appears
      to reduce symptoms in some survivors of sexual abuse, there is an absence of
      clear evidence of treatment efficacy. Other data point to low consumer
      satisfaction with treatment, the absence of evidence for a consistent symptom
      presentation in survivors of sexual abuse that confounds standardizing treatment
      approaches, and iatrogenic effects of some forms of treatment. The authors
      conclude that, at this time, there is little empirical data to support the
      development of standards of practice for treating women who have been sexually
      abused as children.

PMID- 9148883
TI  - Scientific status of the concept of continuing emotional propensity for sexually
      aberrant acts.
AB  - Continuing emotional propensity for sexually aberrant acts and similar concepts
      have a central role in the prosecution of sex offenders. This article examines
      the theoretical and scientific viability of such concepts, focusing on child
      molestation. It is shown that neither theoretical nor scientific underpinnings
      exist, although there is broad clinical agreement on the existence in some
      offenders of "something more" than just a pattern of continuing behavior. Both
      the DSM-IV and addiction models of sex offending capture this viewpoint, and it
      is suggested that clinical/forensic assessment for the presence of a continuing
      emotional propensity rely on these sources until a scientific foundation can be
      laid.

PMID- 9148884
TI  - Self-mutilation and suicide attempt: distinguishing features in prisoners.
AB  - Nonlethal forms of self-injury are often discussed together with suicide attempts
      as though they belonged on a continuum of self-harm. Both types of self-injury
      are common in prisons, which have a predominantly male population; however, most
      studies of nonlethal self-injury have been done with female subjects. This
      exploratory study tested the hypothesis that prisoners who injured themselves
      without intending to die would differ clinically from prisoners who had attempted
      suicide. Inmates admitted to the prison unit of a public hospital for treatment
      of self-inflicted wounds or who had a history of previous self-injury were
      administered a standardized intake protocol by the first author, which included
      asking about their intent at the time they injured themselves. Patients were
      classified as self-mutilators or suicide attempters on the basis of intent.
      Fifteen patients reported that they had attempted to take their own lives, while
      16 reported other reasons for harming themselves. Suicide attempt was associated
      with adult affective disorder 13/15 versus 2/16 mutilators); self-mutilation with
      a history of childhood hyperactivity (12/16 versus 1/15 suicide attempters) and a
      mixed dysthymia/anxiety syndrome that began in childhood or early adolescence
      (9/16). Prison self-mutilators and suicide attempters had very different clinical
      presentations and histories. The history of childhood hyperactivity in self
      mutilators deserves further study in both correctional and noncorrectional
      populations.

PMID- 9148885
TI  - Beyond the black letter of the law: an empirical study of an individual judge's
      decision process for civil commitment hearings.
AB  - To study the role of parens patriae and "police powers" considerations in an
      individual judge's civil commitment decisions, the judge's reports of the impact
      of various characteristics of the patient were analyzed. The validity of this
      methodology was tested by comparing it to an alternative technique based on
      objective statistical analysis of the dependence of the judge's decisions upon
      patient characteristics. A probate court judge filled out a questionnaire after
      each civil commitment hearing over which he presided during a seven-month study.
      For each of 26 decisions, the judge rated the patient on 26 features and
      indicated the impact of each feature on the decision. The judge's responses were
      analyzed to measure the role of various statutory and nonstatutory considerations
      (expressed as patient characteristics) in the judge's decisions. Results using
      self-reported impacts are compared with an objective, statistical
      characterization of the judge's decision-making policy. As in previous studies,
      the parens patriae model more closely described the individual judge's decision
      process than the "police powers" model. Contextual variables (e.g., the patient's
      family favoring commitment) also were influential. Results with the two methods
      were similar. The methodology developed here can be used not only in further
      research on judicial commitment decisions but also to educate judges and other
      decision-makers individually faced with potentially tragic choices as to their
      personal implicit decision-making strategies.

PMID- 9148886
TI  - Group dynamics in forensic pretrial decision-making.
AB  - This study examines how forensic evaluators' opinions that pertain to diagnosis,
      competency to stand trial, and criminal responsibility (Maryland's version of the
      not guilty by reason of insanity plea) are rendered at a state forensic hospital
      for defendants pleading not criminally responsible. Pretrial evaluations
      completed independently by a psychiatrist, a psychologist, and a social worker
      were presented at a forensic staff conference where psychiatrist and
      psychologists openly "voted" on diagnosis, competency to stand trial, and
      criminal responsibility. These results were then sent to the court. The purpose
      of this study was to assess the clinicians' level of agreement and the role that
      conformity played in the decision-making process. A sample of twenty court
      ordered pretrial evaluations of defendants examined at the hospital between March
      and June 1991, with evaluators' opinions generated by a secret ballot, were
      compared with a matched control group from an earlier time, when opinions were
      generated by open ballot. The study was designed to compare the opinions of
      forensic evaluators in the issues of diagnosis, competency to stand trial, and
      criminal responsibility between the two samples. The defendants in the
      experimental group and the control group were matched on the basis of age, race,
      sex, and offense. It was hypothesized that with secret ballot voting there would
      be a greater disparity of agreement regarding diagnosis, competency to stand
      trial, and criminal responsibility opinions compared with the open method of
      voting. However, the results of this study did not support that hypothesis. There
      was little disparity on forensic opinions rated either by secret or open voting.

PMID- 9148887
TI  - Depression in jailed women defendants and its relationship to their adjudicative
      competence.
AB  - This study examines the relationship between depression, as measured by four
      indices, and jailed women defendants' adjudicative competence ("competency to
      stand trial"). Competence was assessed by the MacArthur Competence Assessment
      Tool-Criminal Adjudication (MacCAT-CA) in three areas: understanding, reasoning,
      and appreciation. Depression was not significantly correlated with any competence
      measure. More depressed women, however, were more likely to feel that they would
      not be treated fairly by the legal system. This finding is consistent with
      research showing that depressed people tend to have pessimistic perceptions. The
      rates of depression were far above the rates in the general female population,
      and many of the participants were clinically depressed. In addition, competence
      generally was negatively correlated with measures of psychoticism, emotional
      withdrawal, and general psychopathology. Implications of the results for
      addressing the mental health needs of women defendants, and for defense attorneys
      and forensic clinicians working with them, are discussed.

PMID- 9148888
TI  - American Psychiatric Association resources document on principles of informed
      consent in psychiatry.

PMID- 9148889
TI  - Clustering and enhanced activity of an inwardly rectifying potassium channel,
      Kir4.1, by an anchoring protein, PSD-95/SAP90.
AB  - An inwardly rectifying potassium channel predominantly expressed in glial cells,
      Kir4.1/KAB-2, has a sequence of Ser-Asn-Val in its carboxyl-terminal end,
      suggesting a possible interaction with an anchoring protein of the PSD-95 family.
      We examined the effects of PSD-95 on the distribution and function of Kir4.1 in a
      mammalian cell line. When Kir4.1 was expressed alone, the channel
      immunoreactivity was distributed homogeneously. In contrast, when co-expressed
      with PSD-95, prominent clustering of Kir4.1 in the cell membrane occurred. Kir4.1
      was co-immunoprecipitated with PSD-95 in the co-expressed cells. Glutathione S
      transferase-fusion protein of COOH terminus of Kir4.1 bound to PSD-95. These
      interactions disappeared when the Ser-Asn-Val motif was deleted. The magnitude of
      whole-cell Kir4.1 current was increased by 2-fold in cells co-expressing Kir4.1
      and PSD-95 compared with cells expressing Kir4. 1 alone. SAP97, another member of
      the PSD-95 family, showed similar effects on Kir4.1. Furthermore, we found that
      Kir4.1 as well as SAP97 distributed not diffusely but clustered in retinal glial
      cells. Therefore, PSD-95 family proteins may be a physiological regulator of the
      distribution and function of Kir4.1 in glial cells.

PMID- 9148890
TI  - The yeast JEM1p is a DnaJ-like protein of the endoplasmic reticulum membrane
      required for nuclear fusion.
AB  - DnaJ-like proteins are functional partners for Hsp70 molecular chaperones.
      Complete nucleotide sequencing of yeast chromosome X has revealed that an open
      reading frame YJL073w encodes a novel member of the DnaJ-like protein family. The
      open reading frame represents a protein of 692 amino acids with a J-domain and
      one putative membrane-spanning segment. An epitope-tagged version of the protein
      was anchored in the endoplasmic reticulum (ER) membrane and its J-domain faced
      the ER lumen. We therefore propose to designate this gene JEM1 (DnaJ-like protein
      of the ER membrane) and to designate its gene product JEM1p. The JEM1 gene is not
      essential for cell growth, but double disruption of the JEM1 gene and the SCJ1
      gene, which encodes another DnaJ-like protein in the ER lumen, causes growth
      arrest at elevated temperature. The Deltajem1 mutant is defective in nuclear
      fusion, karyogamy, during mating. A mutant JEM1p carrying a mutation in the
      highly conserved His-Pro-Asp sequence in the J-domain could not complement either
      temperature-sensitive growth of the Deltajem1 Deltascj1 double mutant or defects
      in karyogamy of the Deltajem1 mutant. JEM1p likely assists the functions of BiP,
      Hsp70 in the ER, including karyogamy.

PMID- 9148891
TI  - p53-dependent induction of apoptosis by proteasome inhibitors.
AB  - Proteolysis by the ubiquitin/proteasome pathway controls the intracellular levels
      of a number of proteins that regulate cell proliferation and cell cycle
      progression. To determine whether this pathway of protein turnover was also
      linked to apoptosis, we treated Rat-1 and PC12 cells with specific proteasome
      inhibitors. The peptide aldehydes PSI and MG115, which specifically inhibit the
      chymotrypsin-like activity of the proteasome, induced apoptosis of both cell
      types. In contrast, apoptosis was not induced by inhibitors of lysosomal
      proteases or by an alcohol analog of PSI. The tumor suppressor p53 rapidly
      accumulated in cells treated with proteasome inhibitors, as did the p53-inducible
      gene products p21 and Mdm-2. In addition, apoptosis induced by proteasome
      inhibitors was inhibited by expression of dominant-negative p53, whereas
      overexpression of wild-type p53 was sufficient to induce apoptosis of Rat-1 cells
      in transient transfection assays. Although other molecules may also be involved,
      these results suggest that stabilization and accumulation of p53 plays a key role
      in apoptosis induced by proteasome inhibitors.

PMID- 9148892
TI  - Leptin induces mitogen-activated protein kinase-dependent proliferation of
      C3H10T1/2 cells.
AB  - Leptin, secreted by adipocytes, regulates satiety and energy expenditure. Several
      forms of leptin receptors produced by alternative mRNA splicing are found in many
      tissues, including the hypothalamus, liver, lung, kidney, hematopoietic cells,
      and gonads, suggesting that leptin exerts effects in these tissues. In accordance
      with the distribution of leptin receptors, there is accumulating evidence that
      leptin plays various roles in reproduction, hematopoiesis, and the immune systems
      in addition to the regulation of food intake and energy expenditure. In the
      present study, we examined the in vitro effects of leptin on proliferation of a
      mouse embryonic cell line, C3H10T1/2, and its mechanism of action. Leptin caused
      a dose- and time-dependent increase in mitogen-activated protein kinase (MAPK)
      activity that was accompanied by an increase in C3H10T1/2 cell number. The MAPK
      kinase-1-specific inhibitor PD98059 completely blocked the increases in both MAPK
      activity and cell proliferation caused by leptin. These findings indicate that
      leptin stimulates the proliferation of C3H10T1/2 cells via the MAPK cascade.

PMID- 9148893
TI  - Identification of an adhesion site within the syndecan-4 extracellular protein
      domain.
AB  - The syndecan family of cell surface proteoglycans regulates cell adhesion and
      growth factor signaling by binding components of the extracellular matrix and
      growth factors. To date, all known ligand interactions are via the covalently
      attached glycosaminoglycan chains. To assay for potential extracellular
      interactions via the core proteins directly, the recombinant extracellular domain
      of syndecan-4 (S4ED), one of the four syndecan family members, was tested as a
      substratum for the attachment of mammalian cells. Human foreskin fibroblasts bind
      to mouse S4ED, and both mouse and chicken S4ED can block this binding, with 50%
      inhibition observed between 0.1 and 1 x 10(-7) M. The extracellular domain of
      another syndecan family member, syndecan-1, fails to compete for cell binding to
      mouse S4ED. Amino acids 56-109 of the 120-amino acid mouse S4ED compete fully,
      suggesting that the cell binding domain is within this region. The ability of
      syndecan-4 to interact with molecules at the cell surface via its core protein as
      well as its glycosaminoglycan chains may uniquely regulate the formation of cell
      surface signaling complexes following engagement of this proteoglycan with its
      extracellular ligands.

PMID- 9148894
TI  - Evidence for proton transfer from Glu-46 to the chromophore during the photocycle
      of photoactive yellow protein.
AB  - Photoactive yellow protein (PYP) belongs to the novel group of eubacterial
      photoreceptor proteins. To fully understand its light signal transduction
      mechanisms, elucidation of the intramolecular pathway of the internal proton is
      indispensable because it closely correlates with the changes in the hydrogen
      bonding network, which is likely to induce the conformational changes. For this
      purpose, the vibrational modes of PYP and its photoproduct were studied by
      Fourier transform infrared spectroscopy at -40 degrees C. The vibrational modes
      characteristic for the anionic p-coumaryl chromophore (Kim, M., Mathies, R. A.,
      Hoff, W. D., and Hellingwerf, K. J. (1995) Biochemistry 34, 12669-12672) were
      observed at 1482, 1437, and 1163 cm-1 for PYP. However, the bands corresponding
      to these modes were not observed for PYPM, the blue-shifted intermediate, but the
      1175 cm-1 band characteristic of the neutral p-coumaryl chromophore was observed,
      indicating that the phenolic oxygen of the chromophore is protonated in PYPM. A
      1736 cm-1 band was observed for PYP, but the corresponding band for PYPM was not.
      Because it disappeared in the Glu-46 --> Gln mutant of PYP, this band was
      assigned to the C=O stretching mode of the COOH group of Glu-46. These results
      strongly suggest that the proton at Glu-46 is transferred to the chromophore
      during the photoconversion from PYP to PYPM.

PMID- 9148895
TI  - Phospholipase D activity in PC12 cells. Effects of overexpression of alpha2A
      adrenergic receptors.
AB  - PC12 neuronal cells express a membrane phospholipase D (PLD) activity that is
      detected at similar levels in undifferentiated or differentiated cells. The
      regulation of this activity by agonists was explored. Membrane phospholipase D
      activity was increased by treatment of cells with the phorbol ester phorbol 12
      myristate 13-acetate (PMA) or with nerve growth factor. The ability of PMA to
      activate PLD was confirmed in intact PC12 cells. Basal activity of PLD in
      membranes was reduced in RG20, a PC12 cell line overexpressing the human alpha2A
      adrenergic receptor. PMA did not increase PLD activity in RG20 cells, as assessed
      both in membrane preparations and in intact cells. Cyclic AMP levels did not
      regulate phospholipase D activity in either cell type. However, incubation of
      RG20 cells with the alpha2-adrenergic antagonist rauwolscine or with pertussis
      toxin increased membrane PLD activity and restored activation of PLD by PMA.
      These data suggest that the effects of the overexpressed alpha2A-adrenergic
      receptor on PLD activity are mediated by precoupling of the receptor to the
      heterotrimeric GTP-binding protein, Gi, but are independent of adenylate cyclase
      regulation. The results of this study suggest that membrane phospholipase D
      activity can be negatively regulated via Gi in PC12 cells.

PMID- 9148897
TI  - Identification of phosphorylation sites on neurofilament proteins by
      nanoelectrospray mass spectrometry.
AB  - Neurofilament (NF) proteins are intermediate filaments found in the neuronal
      cytoskeleton. Phosphorylation of these proteins is considered an important factor
      in the assembly of filaments and determination of filament caliber and stability.
      Mammalian neurofilaments are composed of three polypeptide subunits, NF-L, NF-M,
      and NF-H, all of which are phosphorylated. Here we used techniques for the mass
      spectrometric sequencing of proteins from polyacrylamide gels to analyze in vivo
      phosphorylation sites on NF-M and NF-L. Neurofilaments were isolated from rat
      brain and enzymatically digested in gel. The resulting peptides were analyzed and
      sequence data obtained by nanoelectrospray mass spectrometry. Four
      phosphorylation sites have been found in the C-terminal domain of NF-M: serines
      603, 608, 666, and 766. Two of these are found in lysine-serine-proline (KSP)
      motifs and two in the variant motifs, glutamic acid-serine-proline (ESP) and
      valine-serine-proline (VSP). Serine 55 in NF-L was not found to be
      phosphorylated, which confirms the possible role of phosphorylation and
      dephosphorylation of this site in early neurofilament assembly. The techniques
      used enable sequence data and characterization of posttranslational modifications
      to be obtained for each individual subunit directly from polyacrylamide gels.

PMID- 9148896
TI  - Myogenesis and MyoD down-regulate Sp1. A mechanism for the repression of GLUT1
      during muscle cell differentiation.
AB  - Muscle cell differentiation caused a reduction of glucose transport, GLUT1
      glucose transporter expression, and GLUT1 mRNA levels. A fragment of 2.1
      kilobases of the rat GLUT1 gene linked to chloramphenicol acetyltransferase drove
      transcriptional activity in myoblasts, and differentiation caused a decrease in
      transcription. Transient transfection of 5' and 3' deletion constructs showed
      that the fragment -99/-33 of the GLUT1 gene drives transcriptional activity of
      the GLUT1 gene and participates in the reduced transcription after muscle
      differentiation. Electrophoretic mobility shift assays showed the binding of Sp1
      protein to the fragment -102/-37 in the myoblast state but not in myotubes, and
      Sp1 was found to transactivate the GLUT1 promoter. Western blot analysis
      indicated that Sp1 was drastically down-regulated during myogenesis. Furthermore,
      the forced over-expression of MyoD in C3H10T1/2 cells mimicked the effects
      observed during myogenesis, Sp1 down-regulation and reduced transcriptional
      activity of the GLUT1 gene promoter. In all, these data suggest a regulatory
      model in which MyoD activation during myogenesis causes the down-regulation of
      Sp1, which contributes to the repression of GLUT1 gene transcription and,
      therefore, leads to the reduction in GLUT1 expression and glucose transport.

PMID- 9148898
TI  - Human TEF-5 is preferentially expressed in placenta and binds to multiple
      functional elements of the human chorionic somatomammotropin-B gene enhancer.
AB  - We report the cloning of a cDNA encoding the human transcription factor hTEF-5,
      containing the TEA/ATTS DNA binding domain and related to the TEF family of
      transcription factors. hTEF-5 is expressed in skeletal and cardiac muscle, but
      the strongest expression is observed in the placenta and in placenta-derived JEG
      3 choriocarcinoma cells. In correlation with its placental expression, we show
      that hTEF-5 binds to several functional enhansons of the human chorionic
      somatomammotropin (hCS)-B gene enhancer. We define a novel functional element in
      this enhancer comprising tandemly repeated sites to which hTEF-5 binds
      cooperatively. In the corresponding region of the hCS-A enhancer, which is known
      to be inactive, this element is inactivated by a naturally occurring single base
      mutation that disrupts hTEF-5 binding. We further show that the binding of the
      previously described placental protein f/chorionic somatomammotropin enhancer
      factor-1 to TEF-binding sites is disrupted by monoclonal antibodies directed
      against the TEA domain and that this factor is a proteolytic degradation product
      of the TEF factors. These results strongly suggest that hTEF-5 regulates the
      activity of the hCS-B gene enhancer.

PMID- 9148899
TI  - High affinity saturable uptake of oxidized low density lipoprotein by macrophages
      from mice lacking the scavenger receptor class A type I/II.
AB  - Oxidation of low density lipoproteins (LDL) has been implicated as a causal
      factor in the pathogenesis of atherosclerosis. Oxidized LDL has been found to
      exhibit numerous potentially atherogenic properties in vitro, including receptor
      mediated uptake by macrophages. Oxidized LDL is a ligand for the class A
      scavenger receptor type I/II (SR-AI/II), but cross-competition studies with
      cultured macrophages suggested that there is an additional receptor(s) that is
      specific for oxidized LDL and that does not interact with acetyl LDL or other
      chemically modified LDL. A number of macrophage membrane proteins, including
      CD36, FcgammaRII-B2, scavenger receptor BI, and macrosialin/CD68, have been found
      to bind to oxidized LDL in vitro and have been proposed as candidate oxidized LDL
      receptors. However, because of overlapping ligand specificity with the SR-AI/II,
      it has been difficult to evaluate the relative importance of these proteins in
      the uptake of oxidized LDL by macrophages. In the present report, we have studied
      the uptake and degradation of oxidized LDL by macrophages from mice in which the
      SR-AI/II gene had been disrupted. The uptake of acetyl LDL was reduced by more
      than 80% in macrophages from scavenger receptor knockout mice, confirming that
      most of the uptake of acetyl LDL by macrophages can be attributed to this
      receptor. In contrast, the uptake of extensively oxidized LDL was reduced by only
      30% and showed high affinity, saturable uptake with apparent Km of about 5
      microg/ml, similar to that of the SR-AI/II. This indicates that about 70% of the
      uptake of oxidized LDL in macrophages is attributable to an alternate oxidized
      LDL receptor(s). In contrast to findings reported with CD36, mildly oxidized LDL
      was internalized much more slowly than extensively oxidized LDL. Unlabeled
      oxidized LDL, polyinosinic acid, phosphatidylserine-rich liposomes, and LDL or
      bovine albumin modified by fatty acid oxidation products were effective
      competitors for the uptake of radioiodinated oxidized LDL by macrophages from
      knockout mice, whereas acetyl LDL and malondialdehyde-modified LDL were
      relatively poor competitors. This ligand specificity differs from that of CD36
      related (class B) scavenger receptors but is similar to the reported specificity
      of macrosialin/CD68 in ligand blots. However, the rate of uptake of oxidized LDL
      by knockout macrophages was not increased by phorbol ester or in thioglycollate
      elicited macrophages, both of which are expected to increase the amount of
      macrosialin on the cell surface. In macrophages from SR-AI/II knockout mice,
      ligand blots of membrane proteins with iodinated, oxidized, or acetylated LDL
      revealed several bands, with apparent molecular size on SDS-polyacrylamide gel
      electrophoresis of 60, 94, 124, and 210 kDa, but none of the bands were specific
      for oxidized LDL. These results provide direct evidence that a receptor other
      than SR-AI/II is responsible for most of the uptake of oxidized LDL in murine
      macrophages, but further studies are needed to identify the receptor(s) involved.

PMID- 9148900
TI  - CD38 and ADP-ribosyl cyclase catalyze the synthesis of a dimeric ADP-ribose that
      potentiates the calcium-mobilizing activity of cyclic ADP-ribose.
AB  - CD38, a lymphocyte differentiation antigen, is also a bifunctional enzyme
      catalyzing the synthesis of cyclic ADP-ribose (cADPR) from NAD+ and its
      hydrolysis to ADP-ribose (ADPR). An additional enzymatic activity of CD38 shared
      by monofunctional ADP-ribosyl cyclase from Aplysia californica is the exchange of
      the base group of NAD+ (nicotinamide) with various nucleophiles. Both human CD38
      (either recombinant or purified from erythrocyte membranes) and Aplysia cyclase
      were found to catalyze the exchange of ADPR with the nicotinamide group of NAD+
      leading to the formation of a dimeric ADPR ((ADPR)2). The dimeric structure of
      the enzymatic product, which was generated by recombinant CD38 and by CD38(+)
      Namalwa cells from as low as 10 microM NAD+, was demonstrated using specific
      enzyme treatments (dinucleotide pyrophosphatase and 5'-nucleotidase) and mass
      spectrometry analyses of the resulting products. The linkage between the two ADPR
      units of (ADPR)2 was identified as that between the N1 of the adenine nucleus of
      one ADPR unit and the anomeric carbon of the terminal ribose of the second ADPR
      molecule by enzymatic analyses and by comparison with patterns of cADPR cleavage
      with Me2SO:tert-butoxide. Although (ADPR)2 itself did not release Ca2+ from sea
      urchin egg microsomal vesicles, it specifically potentiated the Ca2+-releasing
      activity of subthreshold concentrations of cADPR. Therefore, (ADPR)2 is a new
      product of CD38 that amplifies the Ca2+-mobilizing activity of cADPR.

PMID- 9148901
TI  - Daunorubicin activates NFkappaB and induces kappaB-dependent gene expression in
      HL-60 promyelocytic and Jurkat T lymphoma cells.
AB  - The anthracycline antibiotic, daunorubicin, can induce programmed cell death
      (apoptosis) in cells. Recent work suggests that this event is mediated by
      ceramide via enhanced ceramide synthase activity. Since the generation of
      ceramide has been directly linked with the activation of the transcription
      factor, NFkappaB, this was investigated as a novel target for the action of
      daunorubicin. Here we describe how treatment of HL-60 promyelocytes and Jurkat T
      lymphoma cells with daunorubicin results in the activation of the transcription
      factor NFkappaB. The effect of daunorubicin was evident following 1-2 h
      treatment, which was in contrast to the time course of activation obtained with
      the cytokine, tumor necrosis factor, where NFkappaB activation was detected
      within minutes of cellular stimulation. Activated complexes were shown to contain
      predominantly p50 and p65/RelA subunit components. Daunorubicin also induced
      IkappaB degradation and increased the expression of an NFkappaB-linked reporter
      gene. In addition, the drug was found to strongly potentiate the ability of tumor
      necrosis factor to induce an NFkappaB-linked reporter gene, suggesting a synergy
      between these two agents in this response. These events were sensitive to the
      iron chelator, deferoxamine mesylate (desferal), and the anti-oxidant and metal
      chelator pyrrolidine dithiocarbamate. A structurally related compound,
      mitoxantrone, which, unlike daunorubicin, is unable to undergo redox cycling in
      cells, also activated NFkappaB in a pyrrolidine dithiocarbamate-sensitive manner.
      A specific inhibitor of ceramide synthase, fumonisin B1, had no effect on
      daunorubicin induced NFkappaB activation at a range of concentrations previously
      reported to block apoptosis induced by this drug. However, this agent could
      inhibit increases in ceramide induced by daunorubicin, in addition to blocking
      ceramide synthase activity from HL-60 cells which was activated in response to
      daunorubicin treatment. These data therefore suggest that the effect of
      daunorubicin on NFkappaB is unlikely to involve ceramide, but may involve
      reactive oxygen species generated as a result of endogenous cellular processes
      rather than reductive metabolism of the drug. As NFkappaB may be involved in
      apoptosis, this effect may be an important aspect of the cellular responses to
      this agent.

PMID- 9148902
TI  - Casein kinase II catalyzes tyrosine phosphorylation of the yeast nucleolar
      immunophilin Fpr3.
AB  - In the yeast Saccharomyces cerevisiae, the nucleolar immunophilin, Fpr3, is
      phosphorylated at tyrosine and dephosphorylated by the phosphotyrosine-specific
      phosphoprotein phosphatase, Ptp1. In Ptp1-deficient cells, Fpr3 contains phospho
      Tyr at a single site (Tyr184), but also contains phospho-Ser and phospho-Thr.
      Ser186 (adjacent to Tyr184) is situated within a canonical site for
      phosphorylation by casein kinase II (CKII). Yeast cell lysates contain an
      activity that binds to Fpr3 in vitro and phosphorylates Fpr3 at Ser, Thr, and
      Tyr; this activity was found to be dependent on expression of functional yeast
      CKII. Moreover, purified Fpr3 was phosphorylated on Tyr184 in vitro by either
      purified yeast CKII or purified, bacterially-expressed human CKII. Likewise,
      phosphorylation of Fpr3 at tyrosine in vivo was markedly enhanced in yeast cells
      overexpressing a heterologous (Drosophila) CKII, but was undetectable in yeast
      cells carrying only a temperature-sensitive allele of the endogenous CKII, even
      when the cells were grown at a permissive temperature. Phosphorylation of Fpr3 at
      Tyr184 by CKII in vitro lagged behind phosphorylation of Fpr3 at Ser, and was
      accelerated by pre-phosphorylation of Fpr3 at Ser using CKII. Furthermore,
      synthetic peptides corresponding to the sequence surrounding Tyr184 that
      contained P-Ser (or Glu) at position 186 were much more efficient substrates for
      CKII phosphorylation of Tyr184 than a synthetic peptide containing Ala at
      position 186. These findings indicate that CKII phosphorylates Fpr3 at tyrosine
      and serine both in vivo and in vitro and thus possesses dual specificity. These
      results also indicate that Tyr184 is phosphorylated by CKII via a two-step
      process, in which phosphorylation at the +2 position provides a negatively
      charged specificity determinant that allows subsequent phosphorylation of Tyr184.

PMID- 9148903
TI  - Activation of HIV-1 long terminal repeat transcription and virus replication via
      NF-kappaB-dependent and -independent pathways by potent phosphotyrosine
      phosphatase inhibitors, the peroxovanadium compounds.
AB  - Replication of human immunodeficiency virus type 1 (HIV-1) is increased by
      different cytokines and T cell activators, also known to modulate tyrosine
      phosphorylation levels. A novel class of protein tyrosine phosphatase (PTP)
      inhibitors, peroxovanadium (pV) compounds, were tested for a putative effect on
      HIV-1 long terminal repeat (LTR) activity. We found that these PTP inhibitors
      markedly enhanced HIV-1 LTR activity in 1G5 cells, a stably transfected cell line
      that harbors an HIV-1 LTR-driven luciferase construct. A direct correlation
      between the extent of tyrosine phosphorylation and the level of HIV-1 LTR
      inducibility was seen after treatment with three different pV compounds.
      Transient transfection experiments were carried out in several T cell lines, and
      after addition of pV, a marked increase in HIV-1 LTR activity was measured.
      Monocytoid cells were tested using U937-derived cell lines and were also found to
      be sensitive to the pV-mediated potentiating effect on HIV-1 LTR activity. A
      significant reduction of the pV-mediated increase in HIV-1 LTR activity was seen
      in cells transiently transfected with an HIV-1 LTR-driven luciferase construct
      bearing a mutation in both NF-kappaB binding sites although detectable levels of
      induction remained. Electrophoretic mobility shift assays allowed the
      identification of the nuclear translocation of the NF-kappaB p50.p65 heterodimer
      complex induced by pV compounds. A dominant negative version of the repressor
      IkappaBalpha mutated on serines 32 and 36 impeded pV-induced NF-kappaB-dependent
      luciferase activity. Western blot analysis showed a clear diminution in the
      protein level of IkappaBalpha starting 30 min after pV treatment of Jurkat E6.1
      cells which is indicative of its degradation. On the other hand, no increase in
      tyrosine phosphorylation was observed on IkappaBalpha itself. Finally, we tested
      the PTP inhibitors on four cell lines latently infected with HIV-1 and showed a
      consistent pV-mediated increase in virion production. Thus, our studies suggest
      that pV-mediated activation of HIV-1 LTR activity is controlled by the nuclear
      translocation of the NF-kappaB transcription factor, which is mediated by
      IkappaBalpha serine phosphorylation and degradation, but also by a still
      undefined NF-kappaB-independent pathway.

PMID- 9148904
TI  - Alanine scanning mutagenesis of insulin.
AB  - Alanine scanning mutagenesis has been used to identify specific side chains of
      insulin which strongly influence binding to the insulin receptor. A total of 21
      new insulin analog constructs were made, and in addition 7 high pressure liquid
      chromatography-purified analogs were tested, covering alanine substitutions in
      positions B1, B2, B3, B4, B8, B9, B10, B11, B12, B13, B16, B17, B18, B20, B21,
      B22, B26, A4, A8, A9, A12, A13, A14, A15, A16, A17, A19, and A21. Binding data on
      the analogs revealed that the alanine mutations that were most disruptive for
      binding were at positions TyrA19, GlyB8, LeuB11, and GluB13, resulting in
      decreases in affinity of 1,000-, 33-, 14-, and 8-fold, respectively, relative to
      wild-type insulin. In contrast, alanine substitutions at positions GlyB20,
      ArgB22, and SerA9 resulted in an increase in affinity for the insulin receptor.
      The most striking finding is that B20Ala insulin retains high affinity binding to
      the receptor. GlyB20 is conserved in insulins from different species, and in the
      structure of the B-chain it appears to be essential for the shift from the alpha
      helix B8-B19 to the beta-turn B20-B22. Thus, replacing GlyB20 with alanine most
      likely modifies the structure of the B-chain in this region, but this structural
      change appears to enhance binding to the insulin receptor.

PMID- 9148905
TI  - Secretin promotes osmotic water transport in rat cholangiocytes by increasing
      aquaporin-1 water channels in plasma membrane. Evidence for a secretin-induced
      vesicular translocation of aquaporin-1.
AB  - Although secretin is known to stimulate ductal bile secretion by directly
      interacting with cholangiocytes, the precise cellular mechanisms accounting for
      this choleretic effect are unknown. We have previously shown that secretin
      stimulates exocytosis in cholangiocytes and that these cells transport water
      mainly via the water channel aquaporin-1 (AQP1). In this study, we tested the
      hypothesis that secretin promotes osmotic water movement in cholangiocytes by
      inducing the exocytic insertion of AQP1 into plasma membranes. Exposure of highly
      purified isolated rat cholangiocytes to secretin caused significant, dose
      dependent increases in osmotic membrane water permeability (Pf) (e.g. increased
      by 60% with 10(-7) M secretin), which was reversibly inhibited by the water
      channel blocker HgCl2. Immunoblotting analysis of cholangiocyte membrane
      fractions showed that secretin caused up to a 3-fold increase in the amount of
      AQP1 in plasma membranes and a proportional decrease in the amount of the water
      channel in microsomes, suggesting a secretin-induced redistribution of AQP1 from
      intracellular to plasma membranes. Both the secretin-induced increase in
      cholangiocyte Pf and AQP1 redistribution were blocked by two perturbations that
      inhibit secretin-stimulated exocytosis in cholangiocytes, i.e. treatment with
      colchicine and exposure at low temperatures (20 and 4 degrees C). Our results
      demonstrate that secretin increases AQP1-mediated Pf in cholangiocytes. Moreover,
      our studies implicate the microtubule-dependent vesicular translocation of AQP1
      water channels to the plasma membrane, a mechanism that appears to be essential
      for secretin-induced ductal bile secretion and suggests that AQP1 can be
      regulated by membrane trafficking.

PMID- 9148906
TI  - Desensitization and sequestration of human m2 muscarinic acetylcholine receptors
      by autoantibodies from patients with Chagas' disease.
AB  - Chronic Chagas' disease is associated with pathologic changes of the
      cardiovascular, digestive, and autonomic nervous system, culminating in autonomic
      denervation and congestive heart failure. Previously, circulating autoantibodies
      that activate signaling by cardiac muscarinic acetylcholine receptors (mAChRs)
      have been described. However, it remains unclear whether the chagasic IgGs
      directly interact with the m2 mAChRs (predominant cardiac subtype), and, if so,
      whether chronic exposure of the mAChRs to such activating IgGs would result in
      receptor desensitization. Here we performed studies with purified and
      reconstituted hm2 mAChRs and demonstrate that IgGs from chagasic serum
      immunoprecipitated the mAChRs in a manner similar to an anti-m2 mAChR monoclonal
      antibody tested in parallel. The chagasic antibodies did not directly interact
      with the ligand binding site, because the binding of radiolabeled antagonist was
      unchanged by the addition of the chagasic IgG. In intact cells stably expressing
      the hm2 mAChR, the chagasic IgGs, but not normal IgGs, mimicked the ability of
      the agonist acetylcholine to induce two effects associated with agonist-induced
      receptor desensitization: a decrease in affinity for agonist binding to m2 mAChR
      and sequestration of the hm2 mAChRs from the cell surface. The results
      demonstrate that the chagasic IgGs can directly interact with and desensitize m2
      mAChRs and provide support for the hypothesis of autoimmune mechanisms having a
      role in the pathogenesis of Chagas' cardioneuromyopathy.

PMID- 9148907
TI  - Tissue targeting of angiotensin peptides.
AB  - Angiotensin II (Ang II) is an octapeptide generated by the sequential proteolytic
      action of renin and angiotensin converting enzyme on the glycoprotein
      angiotensinogen. While numerous mammalian tissues have been shown to express some
      or all of the components of the renin-angiotensin system (RAS), the function of
      most of these tissue RAS remains a matter of conjecture. To test for tissue
      specific functions of Ang II and as an alternative to co-expressing all the
      components of RAS, we have engineered a fusion protein that leads to direct Ang
      II release within specific tissues. The angiotensin peptide is cleaved from the
      fusion protein within the secretory pathway by the ubiquitous endoprotease furin
      and is released from the cell by constitutive secretion. Direct injection of an
      expression vector encoding such a fusion protein into rat cardiac ventricles
      results in a highly localized expression of atrial natriuretic peptide mRNA (an
      angiotensin responsive marker of cardiac hypertrophy), demonstrating the utility
      of this approach for local targeting of mature peptides to tissues in animal
      models.

PMID- 9148908
TI  - Lipoprotein lipase reduces secretion of apolipoprotein E from macrophages.
AB  - Macrophages are a significant source of lipoprotein lipase (LPL) and
      apolipoprotein E (apo E) in the developing arterial wall lesion, and each of
      these proteins can importantly modulate lipid and lipoprotein metabolism by
      arterial wall cells. LPL and apo E share a number of cell surface binding sites,
      including proteoglycans, and we have previously shown that proteoglycans are
      important for modulating net secretion of apoprotein E from macrophages. We
      therefore evaluated a potential role for LPL in modulating net secretion of
      macrophage-derived apo E. In pulse-chase experiments, addition of LPL during the
      chase period produced a decrease in secretion of apoprotein E from human monocyte
      derived macrophages, from the human monocytic THP1 cell line, and from J774 cells
      transfected to constitutively express a human apo E cDNA. LPL similarly reduced
      apo E secretion when it was prebound to the macrophage cell surface at 4 degrees
      C. A native LPL particle was required to modulate apo E secretion; addition of
      monomers and aggregates did not produce the same effect. Depletion of cell
      surface proteoglycans by a 72-h incubation in 4-methylumbelliferyl-beta-D
      xyloside did not attenuate the ability of LPL to reduce apo E secretion. However,
      addition of receptor-associated protein attenuated the effect of LPL on apo E
      secretion. Although LPL could mediate removal of exogenously added apo E from the
      culture medium, detailed pulse-chase analysis suggested that it primarily
      prevented release of newly synthesized apo E from the cell layer. Cholesterol
      loading of cells or antibodies to the low density lipoprotein receptor attenuated
      LPL effects on apo E secretion. We postulate that LPL sequesters endogenously
      synthesized apo E at the cell surface by a low density lipoprotein receptor
      dependent mechanism. Such post-translational regulation of macrophage apo E
      secretion by LPL could significantly influence apo E accumulation in arterial
      vessel wall lesions.

PMID- 9148909
TI  - Mutational analysis of the major loop of Bacillus 1,3-1,4-beta-D-glucan 4
      glucanohydrolases. Effects on protein stability and substrate binding.
AB  - The carbohydrate-binding cleft of Bacillus licheniformis 1,3-1, 4-beta-D-glucan 4
      glucanohydrolase is partially covered by the surface loop between residues 51 and
      67, which is linked to beta-strand-(87-95) of the minor beta-sheet III of the
      protein core by a single disulfide bond at Cys61-Cys90. An alanine scanning
      mutagenesis approach has been applied to analyze the role of loop residues from
      Asp51 to Arg64 in substrate binding and stability by means of equilibrium urea
      denaturation, enzyme thermotolerance, and kinetics. The DeltaDeltaGU between
      oxidized and reduced forms is approximately constant for all mutants, with a
      contribution of 5.3 +/- 0.2 kcal.mol-1 for the disulfide bridge to protein
      stability. A good correlation is observed between DeltaGU values by reversible
      unfolding and enzyme thermotolerance. The N57A mutant, however, is more
      thermotolerant than the wild-type enzyme, whereas it is slightly less stable to
      reversible urea denaturation. Mutants with a <2-fold increase in Km correspond to
      mutations at residues not involved in substrate binding, for which the reduction
      in catalytic efficiency (kcat/Km) is proportional to the loss of stability
      relative to the wild-type enzyme. Y53A, N55A, F59A, and W63A, on the other hand,
      show a pronounced effect on catalytic efficiency, with Km > 2-fold and kcat < 5%
      of the wild-type values. These mutated residues are directly involved in
      substrate binding or in hydrophobic packing of the loop. Interestingly, the
      mutation M58A yields an enzyme that is more active than the wild-type enzyme (7
      fold increase in kcat), but it is slightly less stable.

PMID- 9148910
TI  - Expression and characterization of the small subunit of human DNA polymerase
      delta.
AB  - DNA polymerase delta is a heterodimer consisting of a catalytic subunit of 125
      kDa and a small subunit of 50 kDa (p50). We have overexpressed p50 in Escherichia
      coli and have characterized the recombinant protein. p50 was readily
      overexpressed using the pET vector as an insoluble protein. A procedure was
      developed for its purification and renaturation. Examination of the
      physicochemical properties of renatured p50 showed that it is a monomeric protein
      with an apparent molecular weight of 60,000, a Stokes radius of 34 A, and a
      sedimentation coefficient of 4.1 S. Its physical properties were
      indistinguishable from p50 expressed as a soluble protein using the pTACTAC
      vector. Examination of the effects of recombinant p50 on the activity of DNA
      polymerase delta showed that p50 is able to slightly stimulate (about 2-fold) the
      activity of the recombinant 125-kDa catalytic subunit using poly(dA).oligo(dT) as
      a template in the absence of proliferating cell nuclear antigen. In the presence
      of proliferating cell nulear antigen, activity is stimulated about 5-fold. Seven
      stable hybridoma cell lines were established that produced monoclonal antibodies
      against p50. One of these antibodies (13D5) inhibited the activity of calf thymus
      DNA polymerase delta. This antibody, when coupled to a solid support, also was
      found to provide a method for the immunoafffinity purification of recombinant p50
      and of DNA polymerase delta from calf thymus or HeLa extracts.
      Immunoprecipitation and enzyme-linked immunosorbent assays also confirmed that
      p50 interacts with the catalytic subunit of DNA polymerase delta.

PMID- 9148911
TI  - TrkB variants with deletions in the leucine-rich motifs of the extracellular
      domain.
AB  - We have isolated two novel variants involving the extracellular domain of TrkB
      from developing sensory neurons. These variants are generated by alternative
      splicing and lack two or all three of the leucine-rich motifs. Each of these
      variants is expressed as isoforms that possess or lack the intracellular tyrosine
      kinase domain. Fibroblast cell lines stably expressing these variants do not bind
      any of the TrkB ligands (brain-derived neurotrophic factor, neurotrophin-3, and
      neurotrophin-4/5) and neither survive nor undergo morphological transformation in
      response to neurotrophins. These results demonstrate that the leucine-rich motifs
      in TrkB are essential for ligand binding and signaling and indicate that the
      extracellular immunoglobulin-like domains alone are insufficient to confer
      neurotrophin binding to TrkB.

PMID- 9148912
TI  - Characterization of TreR, the major regulator of the Escherichia coli trehalose
      system.
AB  - The pathway of trehalose utilization in Escherichia coli is different at low and
      high osmolarity. The low osmolarity system takes up trehalose as trehalose 6
      phosphate which is hydrolyzed to glucose and glucose 6-phosphate. treB and treC,
      the genes for the enzymes involved, form an operon that is controlled by TreR
      (encoded by treR), the repressor of the system, for which trehalose 6-phosphate
      is the inducer. We have cloned and sequenced treR. The protein contains 315 amino
      acids with a molecular weight of 34,508. TreR was purified and shown to bind as a
      dimer trehalose 6-phosphate and trehalose with a Kd of 10 and 280 microM,
      respectively. The conformations of the protein differ from each other with either
      one or the other substrate-bound. Protease treatment removed the DNA-binding
      domain from the intact protein leaving the dimerization domain (a 29-kDa carboxyl
      terminal fragment) intact. Nuclease protection experiments revealed a palindromic
      sequence located directly upstream of the -35 promoter sequence of treB that
      functions as the operator of the system.

PMID- 9148913
TI  - Interactions between protein kinase C and pleckstrin homology domains. Inhibition
      by phosphatidylinositol 4,5-bisphosphate and phorbol 12-myristate 13-acetate.
AB  - Pleckstrin homology (PH) domains comprised of loosely conserved sequences of
      approximately 100 amino acid residues are a functional protein motif found in
      many signal-transducing and cytoskeletal proteins. We recently demonstrated that
      the PH domains of Tec family protein-tyrosine kinases Btk and Emt (equal to Itk
      and Tsk) interact with protein kinase C (PKC) and that PKC down-regulates Btk by
      phosphorylation. In this study we have characterized the PKC-BtkPH domain
      interaction in detail. Using pure PKC preparations, it was shown that the Btk PH
      domain interacts with PKC with high affinity (KD = 39 nM). Unlike other tested
      phospholipids, phosphatidylinositol 4,5-bisphosphate, which binds to several PH
      domains, competed with PKC for binding to the PH domain apparently because their
      binding sites on the amino-terminal portion of the PH domains overlap. The
      minimal PKC-binding sequence within the Btk PH domain was found to correspond
      roughly to the second and third beta-sheets of the PH domains of known tertiary
      structures. On the other hand, the C1 regulatory region of PKCepsilon containing
      the pseudosubstrate and zinc finger-like sequences was found to be sufficient for
      strong binding to the Btk PH domain. Phorbol 12-myristate 13-acetate (PMA), a
      potent activator of PKC that interacts with the C1 region of PKC, inhibited the
      PKC-PH domain interaction, whereas the bioinactive PMA (4-alpha-PMA) was
      ineffective. The zeta isoform of PKC, which has a single zinc finger-like motif
      instead of the two tandem zinc finger-like sequences present in conventional and
      novel PKC isoforms, does not bind PMA. Thus, as expected, PH domain binding with
      PKCzeta was not interfered with by PMA. Further, inhibitors that are known to
      attack the catalytic domains of serine/threonine kinases did not affect this PKC
      PH domain interaction. In contrast, the presence of physiological concentrations
      of Ca2+ induced less than a 2-fold increase in PKC-PH domain binding. These
      results indicate that PKC binding to PH domains involve the beta2-beta3 region of
      the Btk PH domain and the C1 region of PKC, and agents that interact with either
      of these regions (i.e. phosphatidylinositol 4,5-bisphosphate binding to the PH
      domain and PMA binding to the C1 region of PKC) might act to regulate PKC-PH
      domain binding.

PMID- 9148914
TI  - Specificity and stoichiometry of the Arabidopsis H+/amino acid transporter AAP5.
AB  - The H+-dependent AAP5 amino acid transporter from Arabidopsis thaliana was
      expressed in Xenopus oocytes, and we used radiotracer flux and electrophysiology
      methods to investigate its substrate specificity and stoichiometry. Inward
      currents of up to 9 microA were induced by a broad spectrum of amino acids,
      including anionic, cationic, and neutral amino acids. The apparent affinity of
      AAP5 for amino acids was influenced by the position of side chain branches, bulky
      ring structures, and charged groups. The maximal current was dependent on amino
      acid charge, but was relatively independent of amino acid structure. A detailed
      kinetic analysis of AAP5 using lysine, alanine, glutamate, and histidine revealed
      H+-dependent differences in the apparent affinity constants for each substrate.
      The differences were correlated to the effect of H+ concentration on the net
      charge of each amino acid and suggested that AAP5 transports only the neutral
      species of histidine and glutamate. Stoichiometry experiments, whereby the uptake
      of 3H-labeled amino acid and net inward charge were simultaneously measured in
      voltage-clamped oocytes, showed that the charge:amino acid stoichiometry was 2:1
      for lysine and 1:1 for alanine, glutamate, and histidine. The results confirm
      that histidine is transported in its neutral form and show that the positive
      charge on lysine contributes to the magnitude of its inward current. Thus, the
      transport stoichiometry of AAP5 is 1 H+:1 amino acid irrespective of the net
      charge on the transported substrate. Structural features of amino acid molecules
      that are involved in substrate recognition by AAP5 are discussed.

PMID- 9148915
TI  - Folding of the glucocorticoid receptor by the reconstituted Hsp90-based chaperone
      machinery. The initial hsp90.p60.hsp70-dependent step is sufficient for creating
      the steroid binding conformation.
AB  - Rabbit reticulocyte lysate contains a multiprotein chaperone system that
      assembles steroid receptors into a complex with hsp90. The glucocorticoid
      receptor (GR) is bound to hsp90 via its hormone binding domain (HBD), which must
      be associated with hsp90 to have a steroid binding conformation. Recently, we
      have reconstituted a receptor.hsp90 heterocomplex assembly system with purified
      rabbit hsp90 and hsp70 and bacterially expressed human p23 and p60 (Dittmar, K.
      D., Hutchison, K. A., Owens-Grillo, J. K., and Pratt, W. B. (1996) J. Biol. Chem.
      271, 12833-12839). In this work we show that when the GR is incubated with hsp90,
      hsp70, and p60, steroid binding sites are generated despite the absence of p23.
      In this minimal reconstituted system, the GR is incubated with the chaperones in
      the presence of [3H]triamcinolone acetonide ([3H]TA), which binds to the receptor
      as GR.hsp90 complexes are formed. When molybdate or p23 is also present during
      the incubation with chaperones at 30 degrees C, the formation of steroid binding
      sites can be assayed by incubating the washed GR with [3H]TA after heterocomplex
      assembly at 30 degrees C. However, in the absence of p23 or molybdate, rapid
      disassembly of GR.hsp90 complexes apparently occurs simultaneously with assembly,
      such that [3H]TA must be present during the assembly process to trap evidence of
      conversion of the GR HBD from a non-steroid binding to a steroid binding
      conformation. Mixture of purified rabbit hsp90 and hsp70 with bacterial lysate
      containing human p60 results in spontaneous formation of an hsp90.p60.hsp70
      complex that can be adsorbed with anti-p60 antibody, and the resulting immune
      complex converts the GR HBD to a steroid binding state in an ATP-dependent and K+
      dependent manner. When the GR is incubated with hsp90, hsp70, and p60 in the
      presence of the hsp90-binding antibiotic geldanamycin, GR.hsp90.p60. hsp70
      complexes are formed, but they have no steroid binding activity. Our data suggest
      that hsp90, hsp70, and p60 work together as a chaperone complex that possesses
      all of the folding/unfolding activity necessary to generate the high affinity
      steroid binding conformation of the receptor.

PMID- 9148916
TI  - Rab7 regulates transport from early to late endocytic compartments in Xenopus
      oocytes.
AB  - Rab7 has been shown to localize to late endosomes and to mediate transport from
      early to late endosome/lysosome in mammalian cells and in yeast. We developed a
      novel assay to quantify transport from early to late endosomes using the Xenopus
      oocyte. Oocytes were pulsed with avidin after which the oocytes were incubated to
      allow avidin transport to a late compartment. The oocytes were then allowed to
      internalize biotin-horseradish peroxidase (HRP). The oocytes were then injected
      with test proteins and incubated further to allow transport of biotin-HRP from
      early endosomes to late endosomal/lysosomal compartments. Transport was
      quantified by assessing the formation of HRP-biotin-avidin complexes. Injection
      of Rab7:wild-type (WT) and Rab7:Q67L, a GTPase defective mutant, stimulated
      transport. Rab5:WT had no effect. Rab7:WT-stimulated transport was inhibited by
      nocodazole, suggesting a role for intact microtubules. Wortmannin, a
      phosphatidylinositol 3-kinase inhibitor, blocked Rab7:WT-stimulated transport,
      but Rab7:Q67L-stimulated transport was unaffected by the drug. Rab7:Q67L is
      constitutively activated and may not require phosphatidylinositol 3-kinase
      activity for activation. Rab7-stimulated transport requires N-ethylmaleimide
      sensitive factor (NSF) activity as transport was blocked by N-ethylmaleimide and
      ATPase defective NSF mutants. Our results indicate that sequentially acting
      endocytic Rab GTPases utilize similar factors although their modes of action may
      be different.

PMID- 9148917
TI  - Thyroid hormone-mediated enhancement of heterodimer formation between thyroid
      hormone receptor beta and retinoid X receptor.
AB  - A subset of nuclear receptors, including those for thyroid hormone (TR), retinoic
      acid, vitamin D3, and eicosanoids, can form heterodimers with the retinoid X
      receptor (RXR) on DNA regulatory elements in the absence of their cognate
      ligands. In a mammalian two-hybrid assay, we have found that recruitment of a
      VP16-RXR chimera by a Gal4-TRbeta ligand-binding domain fusion is enhanced up to
      50-fold by thyroid hormone (T3). This was also observed with a mutant fusion,
      Gal4-TR(L454A), lacking ligand-inducible activation function (AF-2) and unable to
      interact with putative coactivators, suggesting that the AF-2 activity of TR or
      intermediary cofactors is not involved in this effect. The wild-type and mutant
      Gal4-TR fusions also exhibited hormone-dependent recruitment of RXR in yeast.
      Hormone-dependent recruitment of RXR was also evident with another Gal4-TR
      mutant, AHTm, which does not interact with the nuclear receptor corepressor N
      CoR, suggesting that ligand-enhanced dimerization is not a result of T3-induced
      corepressor release. Finally, we have shown that the interaction between RXR and
      TR is augmented by T3 in vitro, arguing against altered expression of either
      partner in vivo mediating this effect. We propose that ligand-dependent
      heterodimerization of TR and RXR in solution may provide a further level of
      control in nuclear receptor signaling.

PMID- 9148918
TI  - A novel phosphotyrosine motif with a critical amino acid at position -2 for the
      SH2 domain-mediated activation of the tyrosine phosphatase SHP-1.
AB  - SHP-1 is a protein-tyrosine phosphatase associated with inhibition of activation
      pathways in hematopoietic cells. The catalytic activity of SHP-1 is regulated by
      its two SH2 (Src homology 2) domains; phosphotyrosine peptides that bind to the
      SH2 domains activate SHP-1. The consensus sequence (I/V)XYXX(L/V) is present in
      the cytoplasmic tails of several lymphocyte receptors that interact with the
      second SH2 domain of SHP-1. In several of these receptors, there are two or three
      occurrences of the motif. Here we show that the conserved hydrophobic amino acid
      preceding the phosphotyrosine is critical for binding to and activation of SHP-1
      by peptides corresponding to sequences from killer cell inhibitory receptors. The
      interaction of most SH2 domains with phosphopeptides requires only the
      phosphotyrosine and the three residues downstream of the tyrosine. In contrast,
      the shortest peptide able to bind or activate SHP-1 also included the two
      residues upstream of the phosphotyrosine. A biphosphopeptide corresponding to the
      cytoplasmic tail of a killer cell inhibitory receptor with the potential to
      interact simultaneously with both SH2 domains of SHP-1 was the most potent
      activator of SHP-1. The hydrophobic residue upstream of the tyrosine was also
      critical in the context of the biphosphopeptide. The contribution of a
      hydrophobic amino acid two residues upstream of the tyrosine in the SHP-1-binding
      motif may be an important feature that distinguishes inhibitory receptors from
      those that provide activation signals.

PMID- 9148919
TI  - Regulation of substrate recognition by the MiaA tRNA prenyltransferase
      modification enzyme of Escherichia coli K-12.
AB  - We purified polyhistidine (His6)-tagged and native Escherichia coli MiaA tRNA
      prenyltransferase, which uses dimethylallyl diphosphate (DMAPP) to isopentenylate
      A residues adjacent to the anticodons of most tRNA species that read codons
      starting with U residues. Kinetic and binding studies of purified MiaA were
      performed with several substrates, including synthetic wild-type tRNAPhe, the
      anticodon stem-loop (ACSLPhe) of tRNAPhe, and bulk tRNA isolated from a miaA
      mutant. Gel filtration shift and steady-state kinetic determinations showed that
      affinity-purified MiaA had the same properties as native MiaA and was completely
      active for tRNAPhe binding. MiaA had a Kmapp (tRNA substrates) approximately 3
      nM, which is orders of magnitude lower than that of other purified tRNA
      modification enzymes, a Kmapp (DMAPP) = 632 nM, and a kcatapp = 0.44 s-1. MiaA
      activity was minimally affected by other modifications or nonsubstrate tRNA
      species present in bulk tRNA isolated from a miaA mutant. MiaA modified ACSLPhe
      with a kcatapp/Kmapp substrate specificity about 17-fold lower than that for
      intact tRNAPhe, mostly due to a decrease in apparent substrate binding affinity.
      Quantitative Western immunoblotting showed that MiaA is an abundant protein in
      exponentially growing bacteria (660 monomers per cell; 1.0 microM concentration)
      and is present in a catalytic excess. However, MiaA activity was strongly
      competitively inhibited for DMAPP by ATP and ADP (Kiapp = 0.06 microM),
      suggesting that MiaA activity is inhibited substantially in vivo and that DMAPP
      may bind to a conserved P-loop motif in this class of prenyltransferases. Band
      shift, filter binding, and gel filtration shift experiments support a model in
      which MiaA tRNA substrates are recognized by binding tightly to MiaA multimers
      possibly in a positively cooperative way (Kdapp approximately 0.07 microM).

PMID- 9148920
TI  - Twin hydroxymethyluracil-A base pair steps define the binding site for the DNA
      binding protein TF1.
AB  - The DNA-bending protein TF1 is the Bacillus subtilis bacteriophage SPO1-encoded
      homolog of the bacterial HU proteins and the Escherichia coli integration host
      factor. We recently proposed that TF1, which binds with high affinity (Kd was
      approximately 3 nM) to preferred sites within the hydroxymethyluracil (hmU)
      containing phage genome, identifies its binding sites based on sequence-dependent
      DNA flexibility. Here, we show that two hmU-A base pair steps coinciding with two
      previously proposed sites of DNA distortion are critical for complex formation.
      The affinity of TF1 is reduced 10-fold when both of these hmU-A base pair steps
      are replaced with A-hmU, G-C, or C-G steps; only modest changes in affinity
      result when substitutions are made at other base pairs of the TF1 binding site.
      Replacement of all hmU residues with thymine decreases the affinity of TF1
      greatly; remarkably, the high affinity is restored when the two hmU-A base pair
      steps corresponding to previously suggested sites of distortion are reintroduced
      into otherwise T-containing DNA. T-DNA constructs with 3-base bulges spaced apart
      by 9 base pairs of duplex also generate nM affinity of TF1. We suggest that twin
      hmU-A base pair steps located at the proposed sites of distortion are key to
      target site selection by TF1 and that recognition is based largely, if not
      entirely, on sequence-dependent DNA flexibility.

PMID- 9148921
TI  - Identification of CRAMP, a cathelin-related antimicrobial peptide expressed in
      the embryonic and adult mouse.
AB  - Cathelicidins are the precursors of potent antimicrobial peptides that have been
      identified in several mammalian species. Prior work has suggested that members of
      this gene family can participate in host defense through their antimicrobial
      effects and activate mesenchymal cells during wound repair. To permit further
      study of these proteins a reverse transcriptase-polymerase chain reaction
      approach was used to identify potential mouse homologs. A full-length 562-base
      pair cDNA clone was obtained encoding an NH2-terminal prepro domain homologous to
      other cathelicidins and a unique COOH-terminal peptide. This gene, named Cramp
      for cathelin-related antimicrobial peptide, was mapped to chromosome 9 at a
      region of conserved synteny to which genes for cathelicidins have been mapped in
      pig and man. Northern blot analysis detected a 1-kilobase transcript that was
      expressed in adult bone marrow and during embryogenesis as early as E12, the
      earliest stage of blood development. Reverse transcriptase-polymerase chain
      reaction also detected CRAMP expression in adult testis, spleen, stomach, and
      intestine but not in brain, liver, heart, or skeletal muscle. To evaluate further
      the expression and function of CRAMP, a peptide corresponding to the predicted
      COOH-terminal region was synthesized. CD spectral analysis showed that CRAMP will
      form an amphipathic alpha-helix similar to other antimicrobial peptides.
      Functional studies showed CRAMP to be a potent antibiotic against Gram-negative
      bacteria by inhibiting growth of a variety of bacterial strains (minimum
      inhibitory concentrations 0.5-8.0 microM) and by permeabilizing the inner
      membrane of Escherichia coli directly at 1 microM. Antiserum against CRAMP
      revealed abundant expression in myeloid precursors and neutrophils. Thus, CRAMP
      represents the first antibiotic peptide found in cells of myeloid lineage in the
      mouse. These data suggest that inflammatory cells in the mouse can use a
      nonoxidative mechanism for microbial killing and permit use of the mouse to study
      the role such peptides play in host defense and wound repair.

PMID- 9148922
TI  - Function of disintegrin-like/cysteine-rich domains of atrolysin A. Inhibition of
      platelet aggregation by recombinant protein and peptide antagonists.
AB  - Snake venom hemorrhagic metalloproteinase toxins that have metalloproteinase,
      disintegrin-like and cysteine-rich domains are significantly more potent than
      toxins with only a metalloproteinase domain. The disintegrin-like domains of
      these toxins differ from the disintegrin peptides found in crotalid and viperid
      venoms by the nature of their different disulfide bond structure and, in lieu of
      the disintegrins' signature Arg-Gly-Asp (RGD) integrin binding sequence, there is
      an XXCD disulfide-bonded cysteinyl sequence in that region. Due to these apparent
      differences, the contribution to the overall function of the hemorrhagic
      metalloproteinases by the disintegrin-like domain has been unknown. In this
      investigation we have expressed in insect cells the disintegrin-like/cysteine
      rich (DC) domains of the Crotalus atrox hemorrhagic metalloproteinase atrolysin A
      and demonstrated that the recombinant protein (A/DC) can inhibit collagen- and
      ADP-stimulated platelet aggregation. Using synthetic peptides, we have evidence
      that the region of the disintegrin-like domain that is positionally analogous to
      the RGD loop of the disintegrins is the site responsible for inhibition of
      platelet aggregation. For these synthetic peptides to have significant inhibitory
      activity, the -RSECD- cysteinyl residue must be constrained by participation in a
      disulfide bond with another cysteinyl residue. The two acidic amino acids
      adjacent to the middle cysteinyl residue in these peptides are also important for
      biological activity. These studies emphasize a functional role for the
      disintegrin-like domain in toxins and suggest structural possibilities for the
      design of antagonists of platelet aggregation.

PMID- 9148923
TI  - Quantitation of the pool of cholesterol associated with acyl-CoA:cholesterol
      acyltransferase in human fibroblasts.
AB  - The esterification of cholesterol in homogenates of human fibroblasts was
      explored as a means of estimating the size of the pool of cholesterol associated
      with the endoplasmic reticulum (ER) in vivo. The rationale was that the acyl
      coenzyme A:cholesterol acyltransferase (ACAT) in homogenates should have access
      only to cholesterol associated with the (rough) ER membrane fragments in which it
      resides. Reacting whole homogenates to completion with an excess of [14C]oleoyl
      CoA converted approximately 0.1-2% of total cell-free cholesterol to
      [14C]cholesteryl esters. Control studies indicated that membranes not associated
      with ACAT did not contribute cholesterol to this reaction. The extent of in vitro
      cholesterol esterification varied with pretreatment of the cells. Exposing intact
      cells to serum lipoproteins, oxysterols, or sphingomyelinase increased
      cholesterol esterification in homogenates severalfold; exposing the cells to
      mevinolin or cholesterol oxidase had the opposite effect. The variation in
      cholesterol esterification did not correlate with either the total cellular
      cholesterol or the intrinsic activity of ACAT, neither of which was changed
      significantly by the pretreatments. Rather, the total amount of cholesterol
      esterified in homogenates paralleled the rate of cholesterol esterification in
      the corresponding intact cells. The pool of cholesterol esterified in vitro
      therefore appears to reflect that associated with the ER in vivo. Since several
      of the mechanisms keeping cell cholesterol under tight feedback control are
      themselves located in the ER, this pool might not only be regulated
      physiologically, but could, in turn, help to regulate homeostatic effector
      pathways.

PMID- 9148924
TI  - Two RNA-binding domains determine the RNA-binding specificity of nucleolin.
AB  - Nucleolin is an abundant nucleolar RNA-binding protein that seems to be involved
      in many aspects of ribosome biogenesis. Nucleolin contains four copies of a
      consensus RNA-binding domain (CS-RBD) found in several other proteins. In vitro
      RNA-binding studies previously determined that nucleolin interacts specifically
      with a short RNA stem-loop structure. Taken individually, none of the four CS
      RBDs interacts significantly with the RNA target, but a peptide that contains the
      first two adjacent CS-RBDs (R12) is sufficient to account for nucleolin RNA
      binding specificity and affinity. The full integrity of these two domains is
      required, since N- or C-terminal deletion abolishes the specific interaction with
      the RNA. Mutation of conserved amino acids within the RNP-1 sequence of CS-RBD 1
      or 2 drastically reduces the interaction with the RNA, whereas mutation of the
      analogous residues in CS-RBDs 3 and 4 has no effect in the context of the R1234G
      protein (which corresponds to the C-terminal end of nucleolin). Our results
      demonstrate that nucleolin RNA-binding specificity is the result of a cooperation
      between two CS-RBDs (RBDs 1 and 2) and also suggests a direct or indirect
      involvement of the RNP-1 consensus sequence of both CS-RBDs in the recognition of
      the RNA target.

PMID- 9148925
TI  - Identification of the CD45-associated 116-kDa and 80-kDa proteins as the alpha-
      and beta-subunits of alpha-glucosidase II.
AB  - CD45 is an abundant, highly glycosylated transmembrane protein-tyrosine
      phosphatase expressed on hematopoietic cells. Herein we demonstrate that two
      proteins of 116 kDa and 80 kDa copurify with CD45 from mouse T cells.
      Microsequence analysis of the 116-kDa protein revealed high similarity to an
      incomplete human open reading frame that has been suggested to correspond to the
      catalytic alpha-subunit of glucosidase II. We determined the nucleotide sequence
      of the mouse cDNA and observed that it encodes a protein product nearly identical
      to its human homologue and shares an active site consensus sequence with Family
      31 glucosidases. Amino acid sequencing of the 80-kDa protein, followed by
      molecular cloning, revealed high homology to human and bovine cDNAs postulated to
      encode the beta-subunit of glucosidase II. Antisera developed to the mouse beta
      subunit allowed us to demonstrate that the interaction between CD45 and
      glucosidase II can be reconstituted in vitro in an endoglycosidase H-sensitive
      manner. The strong interaction between glucosidase II and CD45 may provide a
      paradigm for investigating novel aspects of the biology of these proteins.

PMID- 9148927
TI  - Functional activation of Nedd2/ICH-1 (caspase-2) is an early process in
      apoptosis.
AB  - The ICE/CED-3 family of proteases (caspases) play a central role in the execution
      phase of apoptosis. These proteases are synthesised as precursor molecules that
      require processing at specific aspartate residues to produce the two subunits
      that comprise the active enzyme. The activation of some of these proteases has
      been shown to occur during apoptosis. Here we show that Nedd2/ICH-1 (caspase-2)
      is activated during apoptosis induced by a variety of apoptotic stimuli. This
      activation occurs very early upon treatment of cells with apoptotic agents and
      appears to precede the activation of CPP32 (caspase-3). The activation of Nedd2
      was not seen in cells that are resistant to apoptosis. These observations suggest
      that Nedd2 is an early effector in the pathway leading to cell death. Our
      observations also lend weight to the hypothesis that a group of caspases
      containing long prodomains are the first to be activated in response to apoptotic
      signals and that they lie upstream of a second class of caspases such as CPP32
      containing short or no prodomains.

PMID- 9148926
TI  - The substitution of a single amino acid residue (Ser-116 --> Asp) alters NADP
      containing glucose-fructose oxidoreductase of Zymomonas mobilis into a glucose
      dehydrogenase with dual coenzyme specificity.
AB  - Glucose-fructose oxidoreductase (GFOR, EC 1.1.1.99.-) from the Gram-negative
      bacterium Zymomonas mobilis contains the tightly bound cofactor NADP. Based on
      the revision of the gfo DNA sequence, the derived GFOR sequence was aligned with
      enzymes catalyzing reactions with similar substrates. A novel consensus motif
      (AGKHVXCEKP) for a class of dehydrogenases was detected. From secondary structure
      analysis the serine-116 residue of GFOR was predicted as part of a Rossmann-type
      dinucleotide binding fold. An engineered mutant protein (S116D) was purified and
      shown to have lost tight cofactor binding based on (a) altered tryptophan
      fluorescence; (b) lack of NADP liberation through perchloric acid treatment of
      the protein; and (c) lack of GFOR enzyme activity. The S116D mutant showed
      glucose dehydrogenase activity (3.6 +/- 0.1 units/mg of protein) with both NADP
      and NAD as coenzymes (Km for NADP, 153 +/- 9 microM; for NAD, 375 +/- 32 microM).
      The single site mutation therefore altered GFOR, which in the wild-type situation
      contains NADP as nondissociable redox cofactor reacting in a ping-pong type
      mechanism, to a dehydrogenase with dissociable NAD(P) as cosubstrate and a
      sequential reaction type. After prolonged preincubation of the S116D mutant
      protein with excess NADP (but not NAD), GFOR activity could be restored to 70
      units/mg, one-third of wild-type activity, whereas glucose dehydrogenase activity
      decreased sharply. A second site mutant (S116D/K121A/K123Q/I124K) showed no GFOR
      activity even after preincubation with NADP, but it retained glucose
      dehydrogenase activity (4.2 +/- 0.2 units/mg of protein).

PMID- 9148928
TI  - Receptor-mediated ribosome binding to liposomes depends on lipid composition.
AB  - Ribosome binding to the endoplasmic reticulum has been traditionally studied
      using an in vitro assay in which potential ribosome receptors have been purified,
      incorporated into synthetic liposomes, and tested for activity. One such receptor
      (180 kDa; "p180") has been shown to bind ribosomes with high affinity in such a
      system when purified to homogeneity. This result has been challenged by data
      generated in other laboratories, and as a result, doubt has lingered as to the
      authenticity of p180 as a ribosome receptor. The contribution of the major
      difference between these studies, the lipid composition of the liposomes used in
      the in vitro assays, was assessed when identical fractions of rough endoplasmic
      reticulum-specific membrane proteins were incorporated into liposomes composed of
      only phosphatidylcholine (as used in other laboratories), a 50:50 mix of
      phosphatidylcholine and phosphatidylserine (as used in our original studies), or
      lipids derived from canine pancreatic microsomes (as a physiologically relevant
      control). The presence of PS was found to be crucial for the incorporation into
      and ribosome binding activity of p180 in liposomes. These observations are
      compatible with published studies on the importance of acidic phospholipids in
      ribosome binding to intact microsomes and reconcile the apparently conflicting in
      vitro results surrounding the assignment of p180 as a ribosome receptor.

PMID- 9148929
TI  - The structure of the gene for murine CTP:phosphocholine cytidylyltransferase,
      Ctpct. Relationship of exon structure to functional domains and identification of
      transcriptional start sites and potential upstream regulatory elements.
AB  - Phosphatidylcholine (PC) is the most abundant eukaryotic phospholipid and serves
      critical structural and cell-signaling functions. CTP:phosphocholine
      cytidylyltransferase (CT) is the rate-limiting enzyme in the CDP-choline pathway
      of PC biosynthesis, which is utilized by all tissues and is the sole or major PC
      biosynthetic pathway in all non-hepatic cells. Herein, we present the complete
      structure of the murine CT (Ctpct) gene. One P1 genomic clone and six subsequent
      plasmid subclones were isolated and analyzed for the exon-intron organization of
      the Ctpct gene. The gene spans approximately 26 kilobases and is composed of 9
      exons and 8 introns. The exons match the distinct functional domains of the CT
      enzyme: exon 1 is untranslated; exon 2 codes for the nuclear localization signal
      domain; exons 4-7 encompass the catalytic domain; exon 8 codes for the alpha
      helical membrane-binding domain; and exon 9 includes the C-terminal
      phosphorylation domain. Two transcriptional initiation sites, spaced 35
      nucleotides apart, were identified using 5'-rapid amplification of cDNA ends
      polymerase chain reaction. The 5' natural flanking region was found to lack TATA
      or CAAT boxes and to contain GC-rich regions, which are features typical of
      promoters of housekeeping genes. Several sites that have the potential to
      interact with transcription regulatory factors, such as Sp1, AP1, AP2, AP3, Y1,
      and TFIIIA, were identified in the 5'-region of the gene and found to be
      distributed in two distinct clusters. These data will provide the basis for
      future studies on the cis- and trans-acting factors involved in Ctpct gene
      transcription and for the creation of induced mutant mouse models of altered CT
      activity.

PMID- 9148930
TI  - In addition to SEC11, a newly identified gene, SPC3, is essential for signal
      peptidase activity in the yeast endoplasmic reticulum.
AB  - Among the three characterized subunits comprising the signal peptidase complex of
      the yeast Saccharomyces cerevisiae (Sec11p, Spc1p, and Spc2p), only Sec11p is
      essential for cell growth, signal peptide cleavage, and signal peptidase
      dependent protein degradation. Here we report the cloning of the SPC3 gene
      encoding the homolog to mammalian signal peptidase subunit SPC22/23. We find that
      Spc3p is also required for cell growth and signal peptidase activity within the
      yeast endoplasmic reticulum.

PMID- 9148931
TI  - The yeast SPC22/23 homolog Spc3p is essential for signal peptidase activity.
AB  - In eucaryotic cells signal sequences of secretory and membrane proteins are
      cleaved by the signal peptidase complex during their transport into the lumen of
      the endoplasmic reticulum. The signal peptidase complex in yeast consists of four
      subunits. To date, three of these subunits have been functionally characterized.
      One of them, the Sec11p, is essential for viability of yeast cells. It shows
      significant homology to the mammalian SPC18 and SPC21 as well as to bacterial
      leader peptidases. Two other subunits, Spc1p and Spc2p, have been shown to be
      homologous to mammalian SPC12 and SPC25, respectively, and are not essential for
      protein translocation or signal peptide cleavage. We have purified and analyzed
      the fourth subunit of yeast signal peptidase, Spc3p. The protein is essential for
      viability of yeast cells. Depletion of SPC3 leads to accumulation of precursors
      of secretory proteins in vivo and to the loss of the signal peptidase activity in
      vitro. Therefore, in contrast to the bacterial leader peptidases, yeast signal
      peptidase requires a second subunit for its function.

PMID- 9148932
TI  - Distinct regulation of osmoprotective genes in yeast and mammals. Aldose
      reductase osmotic response element is induced independent of p38 and stress
      activated protein kinase/Jun N-terminal kinase in rabbit kidney cells.
AB  - In yeast glycerol-3-phosphate dehydrogenase 1 is essential for synthesis of the
      osmoprotectant glycerol and is osmotically regulated via the high osmolarity
      glycerol (HOG1) kinase pathway. Homologous protein kinases, p38, and stress
      activated protein kinase/Jun N-terminal kinase (SAPK/JNK) are hyperosmotically
      activated in some mammalian cell lines and complement HOG1 in yeast. In the
      present study we asked whether p38 or SAPK/JNK signal synthesis of the
      osmoprotectant sorbitol in rabbit renal medullary cells (PAP-HT25), analogous to
      the glycerol system in yeast. Sorbitol synthesis is catalyzed by aldose reductase
      (AR). Hyperosmolality increases AR transcription through an osmotic response
      element (ORE) in the 5'-flanking region of the AR gene, resulting in elevated
      sorbitol. We tested if AR-ORE is targeted by p38 or SAPK/JNK pathways in PAP-HT25
      cells. Hyperosmolality (adding 150 mM NaCl) strongly induces phosphorylation of
      p38 and of c-Jun, a specific target of SAPK/JNK. Transient lipofection of a
      dominant negative mutant of SAPK kinase, SEK1-AL, into PAP-HT25 cells
      specifically inhibits hyperosmotically induced c-Jun phosphorylation. Transient
      lipofection of a dominant negative p38 kinase mutant, MKK3-AL, into PAP-HT25
      cells specifically suppresses hyperosmotic induction of p38 phosphorylation. We
      cotransfected either one of these mutants or their empty vector with an AR-ORE
      luciferase reporter construct and compared the hyperosmotically induced increase
      in luciferase activity with that in cells lipofected with only the AR-ORE
      luciferase construct. Hyperosmolality increased luciferase activity equally (5-7
      fold) under all conditions. We conclude that hyperosmolality induces p38 and
      SAPK/JNK cascades in mammalian renal cells, analogous to inducing the HOG1
      cascade in yeast. However, activation of p38 or SAPK/JNK pathways is not
      necessary for transcriptional regulation of AR through the ORE. This finding
      stands in contrast to the requirement for the HOG1 pathway for hyperosmotically
      induced activation of yeast GPD1.

PMID- 9148933
TI  - Mutation of residue Phe97 to Leu disrupts the central allosteric pathway in
      Scapharca dimeric hemoglobin.
AB  - Residue Phe97, which is thought to play a central role in the cooperative
      functioning of Scapharca dimeric hemoglobin, has been mutated to leucine to test
      its proposed role in mediating cooperative oxygen binding. This results in an 8
      fold increase in oxygen affinity and a marked decrease in cooperativity. Kinetic
      measurements of ligand binding to the Leu97 mutant suggest an altered unliganded
      (deoxy) state, which has been confirmed by high resolution crystal structures in
      the unliganded and carbon monoxide-liganded states. Analysis of the structures at
      allosteric end points reveals them to be remarkably similar to the corresponding
      wild-type structures, with differences confined to the disposition of residue 97
      side chain, F-helix geometry, and the interface water structure. Increased oxygen
      affinity results from the absence of the Phe97 side chain, whose tight packing in
      the heme pocket of the deoxy state normally restricts the heme from assuming a
      high affinity conformation. The absence of the Phe97 side chain is also
      associated with diminished cooperativity, since Leu97 packs in the heme pocket in
      both states. Residual cooperativity appears to be coupled with observed
      structural transitions and suggests that parallel pathways for communication
      exist in Scapharca dimeric hemoglobin.

PMID- 9148934
TI  - Overexpression of the G1-cyclin gene CLN2 represses the mating pathway in
      Saccharomyces cerevisiae at the level of the MEKK Ste11.
AB  - Basal and induced transcription of pheromone-dependent genes is regulated in a
      cell cycle-dependent way. FUS1, a gene strongly induced after pheromone
      treatment, shows high mRNA levels in mitosis and early G1 phase of the cell
      cycle, a decrease in G1 after START and again an increase in S phase.
      Overexpression of CLN2 was shown to repress the transcript number of pheromone
      dependent genes (1). We asked whether the activities of components of the mating
      pathway fluctuate during the cell cycle. We were also interested in determining
      at what level Cln2 represses the signal transduction machinery. Here we show that
      the activity of the mitogen-activated protein kinase Fus3 indeed fluctuates
      during the cell cycle, reflecting the oscillations of the gene transcripts. CLN2
      overexpression represses Fus3 kinase activity, independently of the phosphatase
      Msg5. Additionally, we show that the activity of the MEK Ste7 also fluctuates
      during the cell cycle. Increased Cln2 levels repress the ability of hyperactive
      STE11 alleles to induce the pathway. G protein-independent activation of Ste11
      caused by an rga1 pbs2 mutation is resistant to high levels of Cln2 kinase.
      Therefore our results suggest that Cln2-dependent repression of the mating
      pathway occurs at the level of Ste11.

PMID- 9148935
TI  - Focal adhesion kinase overexpression enhances ras-dependent integrin signaling to
      ERK2/mitogen-activated protein kinase through interactions with and activation of
      c-Src.
AB  - Cell adhesion to extracellular matrix proteins such as fibronectin (FN) triggers
      a number of intracellular signaling events including the increased tyrosine
      phosphorylation of the cytoplasmic focal adhesion protein-tyrosine kinase (PTK)
      and also the stimulation of the mitogen-activated protein kinase ERK2. Focal
      adhesion kinase (FAK) associates with integrin receptors, and FN-stimulated
      phosphorylation of FAK at Tyr-397 and Tyr-925 promotes the binding of Src family
      PTKs and Grb2, respectively. To investigate the mechanisms by which FAK, c-Src,
      and Grb2 function in FN-stimulated signaling events to ERK2, we expressed wild
      type and mutant forms of FAK in human 293 epithelial cells by transient
      transfection. FAK overexpression enhanced FN-stimulated activation of ERK2
      approximately 4-fold. This was blocked by co-expression of the dominant negative
      Asn-17 mutant Ras, indicating that FN stimulation of ERK2 was Ras-dependent. FN
      stimulated c-Src PTK activity was enhanced by wild type FAK expression, whereas
      FN-stimulated activation of ERK2 was blocked by expression of the c-Src binding
      site Phe-397 mutant of FAK. Expression of the Grb2 binding site Phe-925 mutant of
      FAK enhanced activation of ERK2, whereas a kinase-inactive Arg-454 mutant FAK did
      not. Expression of wild type and Phe-925 FAK, but not Phe-397 FAK, enhanced
      p130(Cas) association with FAK, Shc tyrosine phosphorylation, and Grb2 binding to
      Shc after FN stimulation. FN-induced Grb2-Shc association is another pathway
      leading to activation of ERK2 via Ras. The inhibitory effects of Tyr-397 FAK
      expression show that FAK-mediated association and activation of c-Src is
      essential for maximal signaling to ERK2. Moreover, multiple signaling pathways
      are activated upon the formation of an FAK.c-Src complex, and several of these
      can lead to Ras-dependent ERK2 mitogen-activated protein kinase activation.

PMID- 9148936
TI  - Cooperative effect of calcium binding to adjacent troponin molecules on the thin
      filament-myosin subfragment 1 MgATPase rate.
AB  - The myosin subfragment 1 (S1) MgATPase rate was measured using thin filaments
      with known extents of Ca2+ binding controlled by varying the ratio of native
      cardiac troponin versus an inhibitory troponin with a mutation in the sole
      regulatory Ca2+ binding site of troponin C. Fractional MgATPase activation was
      less than the fraction of troponins that bound Ca2+, implying a cooperative
      effect of bound Ca2+ on cross-bridge cycling. Addition of phalloidin did not
      alter cooperative effects between bound Ca2+ molecules in the presence or absence
      of myosin S1. When the myosin S1 concentration was raised sufficiently to
      introduce cooperative myosin-myosin effects, lower Ca2+ concentrations were
      needed to activate the MgATPase rate. MgATPase activation remained less than Ca2+
      binding, implying a true, not just an apparent, increase in Ca2+ affinity.
      MgATPase activation by Ca2+ was more cooperative than could be explained by
      cooperativeness of overall Ca2+ binding, the discrepancy between Ca2+ binding and
      MgATPase activation, or interactions between myosins. The results suggest the
      thin filament-myosin S1 MgATPase cycle requires calcium binding to adjacent
      troponin molecules and that this binding is cooperatively promoted by a single
      cycling cross-bridge. This mechanism is a potential explanation for Ca2+-mediated
      regulation of cross-bridge kinetics in muscle fibers.

PMID- 9148937
TI  - A 2'-phosphotransferase implicated in tRNA splicing is essential in Saccharomyces
      cerevisiae.
AB  - The last step of tRNA splicing in the yeast Saccharomyces cerevisiae is catalyzed
      by an NAD-dependent 2'-phosphotransferase, which transfers the splice junction 2'
      phosphate from ligated tRNA to NAD to produce ADP-ribose 1"-2" cyclic phosphate.
      We have purified the phosphotransferase about 28,000-fold from yeast extracts and
      cloned its structural gene by reverse genetics. Expression of this gene (TPT1) in
      yeast or in Escherichia coli results in overproduction of 2'-phosphotransferase
      activity in extracts. Tpt1 protein is essential for vegetative growth in yeast,
      as demonstrated by gene disruption experiments. No obvious binding motifs are
      found within the protein. Several candidate homologs in other organisms are
      identified by searches of the data base, the strongest of which is in
      Schizosaccharomyces pombe.

PMID- 9148938
TI  - Cloning and characterization of the Arabidopsis cyclic phosphodiesterase which
      hydrolyzes ADP-ribose 1'',2''-cyclic phosphate and nucleoside 2',3'-cyclic
      phosphates.
AB  - In eukaryotic cells, pre-tRNAs spliced by a pathway that produces a 3',5'
      phosphodiester, 2'-phosphomonoester linkage contain a 2'-phosphate group adjacent
      to the tRNA anticodon. This 2'-phosphate is transferred to NAD to give adenosine
      diphosphate (ADP)-ribose 1", 2"-cyclic phosphate (Appr>p), which is subsequently
      metabolized to ADP-ribose 1"-phosphate (Appr-1"p). The latter reaction is
      catalyzed by a cyclic phosphodiesterase (CPDase), previously identified in yeast
      and wheat. In the work presented here, we describe cloning of the Arabidopsis
      cDNA encoding the 20-kDa CPDase that hydrolyzes Appr>p to Appr-1"p. Properties of
      the bacterially overexpressed and purified Arabidopsis enzyme are similar to
      those of wheat CPDase. In addition to their transformation of Appr>p, both
      enzymes hydrolyze nucleoside 2',3'-cyclic phosphates to nucleoside 2'-phosphates.
      For the Arabidopsis CPDase, the apparent Km values for Appr>p, A>p, C>p, G>p, and
      U>p are 1.35, 1.34, 2.38, 16.86, and 17.67 mM, respectively. Southern analysis
      indicated that CPDase in Arabidopsis is encoded by a single copy gene that is
      expressed, at different levels, in all Arabidopsis organs that were analyzed.
      Indirect immunofluorescence, performed with transfected protoplasts, showed that
      CPDase is localized in the cytoplasm. Based on substrate specificity and products
      generated, the plant enzyme differs from other known cyclic phosphodiesterases.
      The Arabidopsis CPDase does not have recognizable structural similarity or motifs
      in common with proteins deposited in public data bases.

PMID- 9148939
TI  - In crystals of complexes of streptavidin with peptide ligands containing the HPQ
      sequence the pKa of the peptide histidine is less than 3.0.
AB  - The pH dependences of the affinities for streptavidin of linear and cyclic
      peptide ligands containing the HPQ sequence discovered by phage display were
      determined by plasmon resonance measurements. At pH values ranging from 3.0 to
      9.0, the Kd values for Ac-AEFSHPQNTIEGRK-NH2, cyclo-Ac-AE[CHPQGPPC]IEGRK-NH2, and
      cyclo-Ac-AE[CHPQFC]IEGRK-NH2, were determined by competition, and those for cyclo
      [5-S-valeramide-HPQGPPC]K-NH2 were determined directly by equilibrium affinity
      measurements. The Kd values of the ligands increase by an average factor of 3.0
      +/- 0.8 per decrease in pH unit between pH approximately 4.5 and pH approximately
      6.3. Below pH approximately 4.5 there is a smaller increase in Kd values, and
      above pH approximately 6.3 the Kd values become relatively pH-independent. We
      determined the crystal structures of complexes of streptavidin with cyclo-[5-S
      valeramide-HPQGPPC]K-NH2 at pH 1.5, 2.5, 3.0, and 3.5, with cyclo-Ac-[CHPQFC]-NH2
      at pH 2.0, 3.0, 3.6, 4.2, 4.8, and 11.8, with cyclo-Ac-[CHPQGPPC]-NH2 at pH 2.5,
      2.9, and 3.7, and with FSHPQNT at pH 4.0 and compared the structures with one
      another and with those previously determined at other pH values. At pH values
      from 3.0 to 11.8, the electron density for the peptide His side chain is strong,
      flat, and well defined. A hydrogen bond between the Ndelta1 atom of the His and
      the peptide Gln amide group indicates the His of the bound peptide in the
      crystals is uncharged at pH >/= 3.0. By determining selected structures in two
      different space groups, I222 with two crystallographically inequivalent ligand
      sites and I4122 with one site, we show that below pH approximately 3.0, the pKa
      of the bound peptide His in the crystals is influenced by crystal packing
      interactions. The presence of the Ndelta1His-NGln hydrogen bond along with pH
      dependences of the peptide affinities suggest that deprotonation of the peptide
      His is required for high affinity binding of HPQ-containing peptides to
      streptavidin both in the crystals and in solution.

PMID- 9148940
TI  - Cdc42Hs, but not Rac1, inhibits serum-stimulated cell cycle progression at G1/S
      through a mechanism requiring p38/RK.
AB  - Antimitogenic stimuli such as environmental or genotoxic stress, transforming
      growth factor-beta, and the inflammatory cytokines tumor necrosis factor and
      interleukin-1 activate two extracellular signal-regulated kinase (ERK)-based
      signaling pathways: the stress-activated protein kinase (SAPK/JNK) pathway and
      the p38 pathway. Activated p38 phosphorylates transcription factors important in
      the regulation of cell growth and apoptosis, including activating transcription
      factor 2 (ATF2), Max, cAMP response element-binding protein-homologous
      protein/growth arrest DNA damage 153 (CHDP/GADD153). In turn, p38 lies downstream
      of the Rho family GTPases Cdc42Hs and Rac1, as well as at least three mitogen
      activated protein kinase (MAPK)/ERK-kinases (MEKs): MAPK kinases-3, -6, and
      SAPK/ERK-kinase-1. Although many of the stimuli that activate p38 can also
      inhibit cell cycle progression, a clear-cut role for the p38 pathway in cell
      cycle regulation has not been established. Using a quantitative microinjection
      approach, we show here that Cdc42Hs, but not Rac1 or RhoA, can inhibit cell cycle
      progression at G1/S through a mechanism requiring activation of p38. These
      results suggest a novel role for Cdc42Hs in cell cycle inhibition. Furthermore,
      these results suggest that although both Cdc42Hs and Rac1 can activate p38 in
      situ, the effects of Cdc42Hs and Rac1 on cell cycle progression are, in fact,
      quite distinct.

PMID- 9148941
TI  - Subcellular locations of phosphatidylinositol 4-kinase isoforms.
AB  - Phosphatidylinositol (PtdIns) 4-kinase catalyzes the synthesis of PtdIns-4-P, the
      precursor of an array of lipid second messengers generated by additional
      phosphorylation by PtdIns-4-P 5-kinase and PtdIns 3-kinase. PtdIns 4-kinase
      activity is conserved from yeast to higher eukaryotes. Multiple isoforms of
      mammalian PtdIns 4-kinase have been purified, and the activities have been
      detected in almost all subcellular locations. We previously reported the cloning
      and characterization of the first mammalian PtdIns 4-kinase named PI4Kalpha
      (Wong, K., and Cantley, L. C. (1994) J. Biol. Chem. 269, 28878-28884).
      Alternatively spliced forms of PI4Kalpha have also been identified from several
      sources including bovine brain (Gehrmann, T., Vereb, G., Schmidt, M., Klix, D.,
      Meyer, H. E., Varsanyi, M., and Heilmeyer, L. M., Jr. (1996) Biochim. Biophys.
      Acta 1311, 53-63). Recently we isolated a distinct human PtdIns 4-kinase gene,
      named PI4Kbeta, that encodes an enzyme that is wortmannin sensitive (Meyers, R.,
      and Cantley, L. C. (1997) J. Biol. Chem. 272, 4384-4390). Here we report the
      locations of these enzymes and provide evidence for other yet unidentified
      isoforms present in specific organelles. PI4Kalpha is mostly membrane-bound and
      located at the endoplasmic reticulum; whereas PI4Kbeta is in the cytosol and also
      present in the Golgi region. Neither of these isoforms accounts for the major
      type II PtdIns 4-kinase activity detected in the lysosomes and plasma membrane
      fraction.

PMID- 9148942
TI  - Murine SR-BI, a high density lipoprotein receptor that mediates selective lipid
      uptake, is N-glycosylated and fatty acylated and colocalizes with plasma membrane
      caveolae.
AB  - The class B, type I scavenger receptor, SR-BI, was the first molecularly well
      defined cell surface high density lipoprotein (HDL) receptor to be described. It
      mediates transfer of lipid from HDL to cells via selective lipid uptake, a
      mechanism distinct from receptor-mediated endocytosis via clathrin-coated pits
      and vesicles. SR-BI is expressed most abundantly in steroidogenic tissues
      (adrenal gland, ovary), where trophic hormones coordinately regulate its
      expression with steroidogenesis, and in the liver, where it may participate in
      reverse cholesterol transport. Here we have used immunochemical methods to study
      the structure and subcellular localization of murine SR-BI (mSR-BI) expressed
      either in transfected Chinese hamster ovary cells or in murine adrenocortical Y1
      BS1 cells. mSR-BI, an approximately 82-kDa glycoprotein, was initially
      synthesized with multiple high mannose N-linked oligosaccharide chains, and some,
      but not all, of these were processed to complex forms during maturation of the
      protein in the Golgi apparatus. Metabolic labeling with [3H]palmitate and
      [3H]myristate demonstrated that mSR-BI was fatty acylated, a property shared with
      CD36, another class B scavenger receptor, and other proteins that concentrate in
      specialized, cholesterol- and glycolipid-rich plasma membrane microdomains called
      caveolae. OptiPrep density gradient fractionation of plasma membranes established
      that mSR-BI copurified with caveolin-1, a constituent of caveolae; and
      immunofluorescence microscopy demonstrated that mSR-BI colocalized with caveolin
      1 in punctate microdomains across the surface of cells and on the edges of cells.
      Thus, mSR-BI colocalizes with caveolae, and this raises the possibility that the
      unique properties of these specialized cell surface domains may play a critical
      role in SR-BI-mediated transfer of lipids between lipoproteins and cells.

PMID- 9148943
TI  - Amplification of the DNA repair gene O6-methylguanine-DNA methyltransferase
      associated with resistance to alkylating drugs in a mammalian cell line.
AB  - The cytotoxic action of such alkylating chemotherapeutic drugs as 2-chloroethyl-N
      nitrosourea (CNU) derivatives is countered by the repair protein O6-methylguanine
      DNA methyltransferase (MGMT), which removes O6-alkylguanine induced in the DNA by
      these agents. Resistance to these drugs is often correlated with the MGMT levels
      in normal and tumor cells of human and rodent origin. Exposure of mouse 3T3 cells
      to increasing concentrations of CNU, and subsequent selection of resistant cells,
      led to the isolation of clones with 5-10 times higher levels of MGMT activity
      than in the control. The increased MGMT expression at both mRNA and protein
      levels resulted from 5- to 10-fold amplification of the Mgmt gene. Amplification
      of this gene was not associated with concomitant amplification of another
      alkylation damage repair gene, N-methylpurine-DNA glycosylase. No amplification
      of at least three other genes on chromosome 7 (which contains the Mgmt gene) was
      observed in the drug-resistant cells. Furthermore, the amplified Mgmt sequence
      was not associated with a homogeneously staining region, or double minute
      chromosomes, nor present as episomal DNA. In situ hybridization of metaphase
      chromosomes of the drug-resistant cells indicated both translocation and
      localized amplification of the Mgmt gene.

PMID- 9148944
TI  - Contraction-induced changes in acetyl-CoA carboxylase and 5'-AMP-activated kinase
      in skeletal muscle.
AB  - The concentration of malonyl-CoA, a negative regulator of fatty acid oxidation,
      diminishes acutely in contracting skeletal muscle. To determine how this occurs,
      the activity and properties of acetyl-CoA carboxylase beta (ACC-beta), the
      skeletal muscle isozyme that catalyzes malonyl-CoA formation, were examined in
      rat gastrocnemius-soleus muscles at rest and during contractions induced by
      electrical stimulation of the sciatic nerve. To avoid the problem of
      contamination of the muscle extract by mitochondrial carboxylases, an assay was
      developed in which ACC-beta was first purified by immunoprecipitation with a
      monoclonal antibody. ACC-beta was quantitatively recovered in the immunopellet
      and exhibited a high sensitivity to citrate (12-fold activation) and a Km for
      acetyl-CoA (120 microM) similar to that reported for ACC-beta purified by other
      means. After 5 min of contraction, ACC-beta activity was decreased by 90% despite
      an apparent increase in the cytosolic concentration of citrate, a positive
      regulator of ACC. SDS-polyacrylamide gel electrophoresis of both homogenates and
      immunopellets from these muscles showed a decrease in the electrophoretic
      mobility of ACC, suggesting that phosphorylation could account for the decrease
      in ACC activity. In keeping with this notion, citrate activation of ACC purified
      from contracting muscle was markedly depressed. In addition, homogenization of
      the muscles in a buffer free of phosphatase inhibitors and containing the
      phosphatase activators glutamate and MgCl2 or treatment of immunoprecipitated ACC
      beta with purified protein phosphatase 2A abolished the decreases in both ACC
      beta activity and electrophoretic mobility caused by contraction. The rapid
      decrease in ACC-beta activity after the onset of contractions (50% by 20 s) and
      its slow restoration to initial values during recovery (60-90 min) were
      paralleled temporally by reciprocal changes in the activity of the alpha2 but not
      the alpha1 isoform of 5'-AMP-activated protein kinase (AMPK). In conclusion, the
      results suggest that the decrease in ACC activity during muscle contraction is
      caused by an increase in its phosphorylation, most probably due, at least in
      part, to activation of the alpha2 isoform of AMPK. They also suggest a dual
      mechanism for ACC regulation in muscle in which inhibition by phosphorylation
      takes precedence over activation by citrate. These alterations in ACC and AMPK
      activity, by diminishing the concentration of malonyl-CoA, could be responsible
      for the increase in fatty acid oxidation observed in skeletal muscle during
      exercise.

PMID- 9148945
TI  - Alanine-scanning mutations in the "primer grip" of p66 HIV-1 reverse
      transcriptase result in selective loss of RNA priming activity.
AB  - Alanine-scanning mutants of the primer grip region of human immunodeficiency
      virus type 1 reverse transcriptase were tested for their ability to extend RNA
      and DNA versions of the polypurine tract primer, and an oligonucleotide
      representing the 18-nucleotide sequence at the 3' end of tRNALys3. A majority of
      the mutant enzymes were either completely or severely deficient in RNA priming
      activity, but, with only one exception, were able to efficiently extend DNA
      versions of the same primers. The mutant enzymes were able to bind to RNA
      primers, indicating that the defect in RNA priming was not simply a loss of
      binding activity. Mutations at positions 229, 233, and 235 dramatically reduced
      the amount of specific RNase H cleavage at the 3' terminus of the polypurine
      tract, which is required for primer removal. An alanine substitution at position
      232 led to loss of cleavage specificity, although total activity was close to the
      wild-type level. Taken together, these results demonstrate for the first time
      that there are residues in human immunodeficiency virus type 1 reverse
      transcriptase which are specifically involved in protein-nucleic acid
      interactions with RNA primers.

PMID- 9148946
TI  - Detection in living cells of Ca2+-dependent changes in the fluorescence emission
      of an indicator composed of two green fluorescent protein variants linked by a
      calmodulin-binding sequence. A new class of fluorescent indicators.
AB  - We have designed a novel fluorescent indicator composed of two green fluorescent
      protein variants joined by the calmodulin-binding domain from smooth muscle
      myosin light chain kinase. When (Ca2+)4-calmodulin is bound to the indicator (Kd
      = 0.4 nM), fluorescence resonance energy transfer between the two fluorophores is
      attenuated; the ratio of the fluorescence intensity measured at 505 nm to the
      intensity measured at 440 nm decreases 6-fold. Images of microinjected living
      cells demonstrate that emission ratios can be used to monitor spatio-temporal
      changes in the fluorescence of the indicator. Changes in indicator fluorescence
      in these cells are coupled with no discernible lag (<1 s) to changes in the
      cytosolic free Ca2+ ion concentration, ranging from below 50 nM to approximately
      1 microM. This observation suggests that the activity of a calmodulin target with
      a typical 1 nM affinity for (Ca2+)4-calmodulin is responsive to changes in the
      intracellular Ca2+ concentration over the physiological range. It is likely that
      the indicator we describe can be modified to detect the levels of ligands and
      proteins in the cell other than calmodulin.

PMID- 9148947
TI  - Association between v-Src and protein kinase C delta in v-Src-transformed
      fibroblasts.
AB  - In response to the kinase activity of v-Src there is an increase in the membrane
      association of the novel protein kinase C (PKC) isoform PKC delta (Zang, Q.,
      Frankel, P., and Foster, D. A. (1995) Cell Growth Differ. 6, 1367-1373). We
      report here that in v-Src-transformed cells PKC delta co-immunoprecipitates with
      v-Src and is phosphorylated on tyrosine. The tyrosine-phosphorylated PKC delta
      had reduced enzymatic activity relative to the non-tyrosine-phosphorylated PKC
      delta from v-Src-transformed cells. The association between Src and PKC delta was
      dependent upon both an active Src kinase and membrane association. The
      association between c-Src Y527F and PKC delta was substantially enhanced by
      mutating a PKC phosphorylation site at Ser-12 in Src to Ala indicating that PKC
      delta phosphorylation of Src at Ser-12 destabilizes the interaction, possibly in
      a negative feedback loop. These data demonstrate that upon recruitment of PKC
      delta to the membrane in v-Src-transformed cells there is the formation of a
      Src.PKC delta complex in which PKC delta becomes phosphorylated on tyrosine and
      down-regulated.

PMID- 9148948
TI  - Intracellular location of thymidylate synthase and its state of phosphorylation.
AB  - Thymidylate synthase (TS), an enzyme that is essential for DNA synthesis, was
      found to be associated mainly with the nucleolar region of H35 rat hepatoma
      cells, as determined both by immunogold electron microscopy and by
      autoradiography. In the latter case, the location of TS was established through
      the use of [6-3H]5-fluorodeoxyuridine, which forms a tight ternary complex of TS
      with 5-fluorodeoxyuridylate (FdUMP) and 5, 10
      methylenetetrahydrofolylpolyglutamate within the cell. However, with H35 cells
      containing 50-100-fold greater amounts of TS than unmodified H35 cells, the
      enzyme, although still in the nucleus, was located primarily in the cytoplasm as
      shown by autoradiography and immunohistochemistry. In addition, TS was also
      present in mitochondrial extracts of both cell lines, as determined by enzyme
      activity measurements and by ternary complex formation with [32P]FdUMP and 5,10
      methylenetetrahydrofolate. Another unique observation is that the enzyme appears
      to be a phosphoprotein, similar to that found for other proteins associated with
      cell division and signal transduction. The significance of these findings
      relative to the role of TS in cell division remains to be determined, but suggest
      that this enzyme's contribution to the cell cycle may be more complex than
      believed previously.

PMID- 9148949
TI  - Cloning, sequencing, and enzymatic activity of an inducible aldo-keto reductase
      from Chinese hamster ovary cells.
AB  - Treatment of Chinese hamster ovary (CHO) cells by the aldehyde containing calpain
      inhibitor I resulted in the induction of a 35-kDa protein that was partially
      sequenced and shown to be a member of the aldo-keto reductase superfamily (Inoue,
      S., Sharma, R. C., Schimke, R. T., and Simoni, R. D. (1993) J. Biol. Chem. 268,
      5894-5898). Using rapid amplification of cDNA ends polymerase chain reaction, we
      have sequenced the cDNA for this protein (CHO reductase). This enzyme is a new
      member of the aldo-keto reductase superfamily and shows greatest amino acid
      sequence identity to mouse fibroblast growth factor-regulated protein and mouse
      vas deferens protein (92 and 80% sequence identity, respectively). The enzyme
      exhibits about 70% sequence identity with the aldose reductases (ALR2; EC
      1.1.1.21) and about 47% with the aldehyde reductases (ALR1; EC 1.1.1.2). Northern
      analysis showed that it is induced in preference to either ALR1 or ALR2 and RNase
      protection assays showed gene expression in bladder, testis, jejunum, and ovary
      in descending order of expression. The cDNA for this inducible reductase was
      cloned into the pET16b vector and expressed in BL21(DE3) cells. Expressed CHO
      reductase showed kinetic properties distinct from either ALR1 or ALR2 including
      the ability to metabolize ketones. This protein joins a growing number of
      inducible aldo-keto reductases that may play a role in cellular regulation and
      protection.

PMID- 9148950
TI  - Inhibition of NADPH oxidase activation by 4-(2-aminoethyl)-benzenesulfonyl
      fluoride and related compounds.
AB  - The elicitation of an oxidative burst in phagocytes rests on the assembly of a
      multicomponental complex (NADPH oxidase) consisting of a membrane-associated
      flavocytochrome (cytochrome b559), representing the redox element responsible for
      the NADPH-dependent reduction of oxygen to superoxide (O-2), two cytosolic
      components (p47(phox), p67(phox)), and the small GTPase Rac (1 or 2). We found
      that 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF), an irreversible serine
      protease inhibitor, prevented the elicitation of O-2 production in intact
      macrophages and the amphiphile-dependent activation of NADPH oxidase in a cell
      free system, consisting of solubilized membrane or purified cytochrome b559
      combined with total cytosol or a mixture of recombinant p47(phox), p67(phox), and
      Rac1. AEBSF acted at the activation step and did not interfere with the ensuing
      electron flow. It did not scavenge oxygen radicals and did not affect assay
      reagents. Five other serine protease inhibitors (three irreversible and two
      reversible) were found to lack an inhibitory effect on cell-free activation of
      NADPH oxidase. A structure-function study of AEBSF analogues demonstrated that
      the presence of a sulfonyl fluoride group was essential for inhibitory activity
      and that compounds containing an aminoalkylbenzene moiety were more active than
      amidinobenzene derivatives. Exposure of the membrane fraction or of purified
      cytochrome b559, but not of cytosol or recombinant cytosolic components, to
      AEBSF, in the presence of a critical concentration of the activating amphiphile
      lithium dodecyl sulfate, resulted in a marked impairment of their ability to
      support cell-free NADPH oxidase activation upon complementation with untreated
      cytosol or cytosolic components. Kinetic analysis of the effect of varying the
      concentration of each of the three cytosolic components on the inhibitory potency
      of AEBSF indicated that this was inversely related to the concentrations of
      p47(phox) and, to a lesser degree, p67(phox). AEBSF also prevented the amphiphile
      elicited translocation of p47(phox) and p67(phox) to the membrane. These results
      are interpreted as indicating that AEBSF interferes with the binding of p47(phox)
      and/or p67(phox) to cytochrome b559, probably by a direct effect on cytochrome
      b559.

PMID- 9148951
TI  - acrB mutation located at carboxyl-terminal region of gyrase B subunit reduces DNA
      binding of DNA gyrase.
AB  - Mutations that exhibit susceptibility to acriflavine have been isolated and
      classified as acr mutations in Escherichia coli. We cloned the acrB gene, which
      has been identified as a mutation of the gyrB gene, and found a double point
      mutation altering two consecutive amino acids (S759R/R760C) in the COOH-terminal
      region of the gyrase B subunit. The mutant B subunit was found to associate with
      the A subunit to make the quaternary structure, and the reconstituted gyrase
      showed an 80-fold reduction of specific activity in DNA supercoiling assay; the
      sensitivity to acriflavine was not different in the same unit of wild-type and
      mutant gyrases. The mutant enzyme retained intrinsic ATPase activity, but DNA
      dependent stimulation was observed infrequently. A gel shift assay showed that
      acriflavine inhibited the DNA binding of gyrase. The acrB mutation also reduced
      significantly the DNA binding of gyrase but did not change the sensitivity to
      acriflavine. These results revealed that the acrB mutation is related to the
      inhibitory mechanism of acriflavine; and the acriflavine sensitivity of the
      mutant, at least in vitro, is caused mainly by reduction of the enzyme activity.
      Further, our findings suggest that the COOH-terminal region of the B subunit is
      essential for the initial binding of gyrase to the substrate DNA.

PMID- 9148952
TI  - Regulation of mitogen-activated protein kinase phosphatase-1 expression by
      extracellular signal-related kinase-dependent and Ca2+-dependent signal pathways
      in Rat-1 cells.
AB  - Stimulation of Rat-1 cells with lysophosphatidic acid (LPA) or epidermal growth
      factor (EGF) results in a biphasic, sustained activation of extracellular signal
      regulated kinase 1 (ERK1). Pretreatment of Rat-1 cells with either cycloheximide
      or sodium orthovanadate had little effect on the early peak of ERK1 activity but
      potentiated the sustained phase. Cycloheximide also potentiated ERK1 activation
      in Rat-1 cells expressing DeltaRaf-1:ER, an estradiol-regulated form of the
      oncogenic, human Raf-1. Since cycloheximide did not potentiate MEK activity but
      abrogated the expression of mitogen-activated protein kinase phosphatase (MKP-1)
      normally seen in response to EGF and LPA, we speculated that the level of MKP-1
      expression may be an important regulator of ERK1 activity in Rat-1 cells.
      Inhibition of LPA-stimulated MEK and ERK activation with PD98059 and pertussis
      toxin, a selective inhibitor of Gi-protein-coupled signaling pathways, reduced
      LPA-stimulated MKP-1 expression by only 50%, suggesting the presence of
      additional MEK- and ERK-independent pathways for MKP-1 expression. Specific
      activation of the MEK/ERK pathway by DeltaRaf-1:ER had little or no effect on MKP
      1 expression, suggesting that activation of the Raf/MEK/ERK pathway is necessary
      but not sufficient for MKP-1 expression in Rat-1 cells. Activation of PKC played
      little part in growth factor-stimulated MKP-1 expression, but LPA- and EGF
      induced MKP-1 expression was blocked by buffering [Ca2+]i, leading to a
      potentiation of the sustained phase of ERK1 activation without potentiating MEK
      activity. In Rat-1DeltaRaf-1:ER cells, we observed a strong synergy of MKP-1
      expression when cells were stimulated with estradiol in the presence of
      ionomycin, phorbol 12-myristate 13-acetate, or okadaic acid under conditions
      where these agents did not synergize for ERK activation. These results suggest
      that activation of the Raf/MEK/ERK pathway is insufficient to induce expression
      of MKP-1 but instead requires other signals, such as Ca2+, to fully reconstitute
      the response seen with growth factors. In this way, ERK-dependent and 
      independent signals may regulate MKP-1 expression, the magnitude of sustained
      ERK1 activity, and therefore gene expression.

PMID- 9148953
TI  - Regulation of Schizosaccharomyces pombe Wee1 tyrosine kinase.
AB  - Wee1 tyrosine kinase regulates mitosis by carrying out the inhibitory tyrosine 15
      phosphorylation of Cdc2 M-phase inducing kinase. Schizosaccharomyces pombe Wee1
      is a large protein, consisting of a C-terminal catalytic domain of approximately
      350 amino acids preceded by a N-terminal domain of approximately 550 residues.
      The functional properties of the Wee1 N-terminal domain were investigated by
      expressing truncated forms of Wee1 in S. pombe. Both positive and negative
      regulatory domains were identified. Sequences important for Wee1 function were
      mapped to a central region (residues 363-408). This region is not required for
      kinase activity or nuclear localization, suggesting it may be involved in
      substrate recognition. The negative regulatory domain resides in the N-terminal
      third of Wee1, Wee1 constructs lacking this domain are more effective at delaying
      mitosis than wild-type Wee1. The negative regulatory domain contains clusters of
      potential Cdc2 phosphorylation sites. Investigations to monitor the abundance of
      Wee1 mRNA and protein during the cell cycle were also carried out.

PMID- 9148954
TI  - Arrest of mycobacterial phagosome maturation is caused by a block in vesicle
      fusion between stages controlled by rab5 and rab7.
AB  - Mycobacterium tuberculosis and the closely related organism Mycobacterium bovis
      can survive and replicate inside macrophages. Intracellular survival is at least
      in part attributed to the failure of mycobacterial phagosomes to undergo fusion
      with lysosomes. The transformation of phagosomes into phagolysosomes involves
      gradual acquisition of markers from the endosomal compartment. Members of the rab
      family of small GTPases which confer fusion competence in the endocytic pathway
      are exchanged sequentially onto the phagosomal membranes in the course of their
      maturation. To identify the step at which the fusion capability of phagosomes
      containing mycobacteria is compromised, we purified green fluorescent protein
      labeled M. bovis BCG phagosomal compartments (MPC) and compared GTP-binding
      protein profiles of these vesicles with latex bead phagosomal compartments (LBC).
      We report that the MPC do not acquire rab7, specific for late endosomes, even 7
      days postinfection, whereas this GTP-binding protein is present on the LBC within
      hours after phagocytosis. By contrast, rab5 is retained and enriched with time on
      the MPC, suggesting fusion competence with an early endosomal compartment. Prior
      infection of macrophages with M. bovis BCG also affected the dynamics of rab5 and
      rab7 acquisition by subsequently formed LBC. Selective exclusion of rab7, coupled
      with the retention of rab5 on the mycobacterial phagosome, may allow organisms
      from the M. tuberculosis complex to avert the usual physiological destination of
      phagocytosed material.

PMID- 9148955
TI  - The human papillomavirus type 16 E6 and E7 oncoproteins dissociate cellular
      telomerase activity from the maintenance of telomere length.
AB  - The "high risk" subgroup of human papillomaviruses (e.g. HPV-16 and HPV-18)
      infect and induce tumors of mucosal epithelium. These neoplasms, which can
      progress to malignancy, retain and express the papillomavirus E6 and E7
      oncogenes. In vitro, the E6 and E7 proteins associate with the cellular p53 and
      Rb proteins and interfere with their normal growth-regulatory functions. We
      report here that primary human keratinocytes transduced with the HPV-16 E6 gene,
      but not the E7 gene, express significant telomerase activity. However, despite
      this detectable enzymatic activity, E6-transduced cells continue to shorten their
      telomeres during in vitro passaging similar to control cells and to cells
      expressing the E7 and E6+E7 genes. At late passages, however, E7-transduced cells
      partially restore telomere length, although they lack detectable telomerase
      activity, demonstrating that E6-independent, telomerase-independent events
      mediate this change.

PMID- 9148956
TI  - Apparent formation of sodium dodecyl sulfate-stable complexes between serpins and
      3,4-dichloroisocoumarin-inactivated proteinases is due to regeneration of active
      proteinase from the inactivated enzyme.
AB  - Protein proteinase inhibitors of the serpin family were recently reported to form
      SDS-stable complexes with inactive serine proteinases modified at the catalytic
      serine with 3, 4-dichloroisocoumarin (DCI) that resembled the complexes formed
      with the active enzymes (Christensen, S., Valnickova, Z., Thogersen, I. B. ,
      Pizzo, S. V., Nielsen, H. R., Roepstorff, P., and Enghild, J. J. (1995) J. Biol.
      Chem. 270, 14859-14862). The discordance between these findings and other reports
      that similar active site modifications of serine proteinases block the ability of
      serpins to form SDS-stable complexes prompted us to investigate the mechanism of
      complex formation between serpins and DCI-inactivated enzymes. Both neutrophil
      elastase and beta-trypsin inactivated by DCI appeared to form SDS-stable
      complexes with the serpin, alpha1-proteinase inhibitor (alpha1PI), as reported
      previously. However, several observations suggested that such complex formation
      resulted from a reaction not with the DCI enzyme but rather with active enzyme
      regenerated from the DCI enzyme by a rate-limiting hydrolysis reaction. Thus (i)
      complex formation was blocked by active site-directed peptide chloromethyl ketone
      inhibitors; (ii) the kinetics of complex formation indicated that the reaction
      was not second order but rather showed a first-order dependence on DCI enzyme
      concentration and zero-order dependence on inhibitor concentration; and (iii)
      complex formation was accompanied by stoichiometric release of a peptide having
      the sequence SIPPE corresponding to cleavage at the alpha1PI reactive center P1
      P1' bond. Quantitation of kinetic constants for DCI and alpha1PI inactivation of
      human neutrophil elastase and trypsin and for reactivation of the DCI enzymes
      showed that the observed complex formation could be fully accounted for by
      alpha1PI preferentially reacting with active enzyme regenerated from DCI enzyme
      during the reaction. These results support previous findings of the critical
      importance of the proteinase catalytic serine in the formation of SDS-stable
      serpin-proteinase complexes and are in accord with an inhibitory mechanism in
      which the proteinase is trapped at the acyl intermediate stage of proteolysis of
      the serpin as a substrate.

PMID- 9148957
TI  - The transcriptional activators BAS1, BAS2, and ABF1 bind positive regulatory
      sites as the critical elements for adenine regulation of ADE5,7.
AB  - Adenine repression of the purine nucleotide biosynthetic genes in Saccharomyces
      cerevisiae involves down-regulation of the activator protein BAS1 or BAS2 by an
      unknown mechanism. To determine the minimal cis-acting requirements for adenine
      regulation, hybrid promoter constructs were made between ADE5,7 promoter
      fragments and a CYC1-lacZ reporter. A 139-nucleotide fragment containing two BAS1
      binding sites was sufficient to confer adenine regulation on the CYC1-lacZ
      reporter. Analysis of deletion and substitution mutations led to the conclusion
      that the proximal BAS1 binding site is both necessary and sufficient for
      regulation, whereas the distal site augments the function of the proximal site.
      By performing saturation mutagenesis, we found two essential regions that flank
      the proximal site. An ABF1 consensus sequence is within one of these regions, and
      mutations that impaired in vitro ABF1 binding impaired promoter activity in vivo.
      A second region is AT-rich and appears to bind BAS2. No substitution mutations
      led to high level constitutive promoter activity as would be expected from
      removal of an upstream repression sequence. Our results indicate that ABF1, BAS1,
      and BAS2 are required for ADE5,7 promoter function and that adenine repression
      most likely involves activator modification or a negative regulator that does not
      itself bind DNA.

PMID- 9148958
TI  - Interaction of MutS protein with the major and minor grooves of a heteroduplex
      DNA.
AB  - Thermus aquaticus MutS protein is a DNA mismatch repair protein that recognizes
      and binds to heteroduplex DNAs containing mispaired or unpaired bases. Using
      enzymatic and chemical probe methods, we have examined the binding of Taq MutS
      protein to a heteroduplex DNA having a single unpaired thymidine residue. DNase I
      footprinting identifies a symmetrical region of protection 24-28 nucleotides long
      centered on the unpaired base. Methylation protection and interference studies
      establish that Taq MutS protein makes contacts with the major groove of the
      heteroduplex in the immediate vicinity of the unpaired base. Hydroxyl radical and
      1, 10-phenanthroline-copper footprinting experiments indicate that MutS also
      interacts with the minor groove near the unpaired base. Together with the
      identification of key phosphate groups detected by ethylation interference, these
      data reveal critical contact points residing in the major and minor grooves of
      the heteroduplex DNA.

PMID- 9148959
TI  - Activated alleles of yeast SLN1 increase Mcm1-dependent reporter gene expression
      and diminish signaling through the Hog1 osmosensing pathway.
AB  - Two-component signal transduction systems involving histidine autophosphorylation
      and phosphotransfer to an aspartate residue on a receiver molecule have only
      recently been discovered in eukaryotes, although they are well studied in
      prokaryotes. The Sln1 protein of Saccharomyces cerevisiae is a two-component
      regulator involved in osmotolerance. Phosphorylation of Sln1p leads to inhibition
      of the Hog1 mitogen-activated protein kinase osmosensing pathway. We have
      discovered a second function of Sln1p by identifying recessive activated alleles
      (designated nrp2) that regulate the essential transcription factor Mcm1. nrp2
      alleles cause a 5-fold increase in the activity of an Mcm1-dependent reporter,
      whereas deletion of SLN1 causes a 10-fold decrease in reporter activity and a
      corresponding decrease in expression of Mcm1-dependent genes. In addition to
      activating Mcm1p, nrp2 mutants exhibit reduced phosphorylation of Hog1p and
      increased osmosensitivity suggesting that nrp2 mutations shift the Sln1p
      equilibrium toward the phosphorylated state. Two nrp2 mutations map to conserved
      residues in the receiver domain (P1148S and P1196L) and correspond to residues
      implicated in bacterial receivers to control receiver phosphorylation state.
      Thus, it appears that increased Sln1p phosphorylation both stimulates Mcm1p
      activity and diminishes signaling through the Hog1 osmosensing pathway.

PMID- 9148960
TI  - QSR1, an essential yeast gene with a genetic relationship to a subunit of the
      mitochondrial cytochrome bc1 complex, codes for a 60 S ribosomal subunit protein.
AB  - QSR1 (quinol-cytochrome c reductase subunit-requiring) is a highly conserved,
      essential gene in Saccharomyces cerevisiae that was identified through a
      synthetic lethal screen by its genetic relationship to QCR6, the gene for subunit
      6 (Qcr6p) of the mitochondrial cytochrome bc1 complex. The function of the QSR1
      encoded protein (Qsr1p) and its relationship to the QCR6-encoded protein are
      unknown. When yeast cell lysates are fractionated by density gradient
      centrifugation, Qsr1p separates from organelles and sediments with a uniformly
      sized population of particles that are similar to eukaryotic ribosomes upon
      velocity gradient centrifugation. When 40 S and 60 S ribosomal subunits are
      separated on velocity gradients, Qsr1p is found exclusively with the 60 S
      subunits, where it is a stoichiometric component. Extracts prepared from qsr1-1
      cells are defective in in vitro translation assays relative to the wild type. In
      yeast cell lysates in which QCR6 rescues an otherwise lethal qsr1-1 mutation,
      Qcr6p is found only in mitochondria, both in respiratory-competent cells and in
      rho0 cells in which the bc1 complex is no longer present. These results suggest
      that suppression of the qsr1-1 mutation by QCR6 occurs by a trans-relationship
      across the outer mitochondrial membrane.

PMID- 9148961
TI  - Phosphatidylcholine hydrolysis is required for pancreatic cholesterol esterase-
      and phospholipase A2-facilitated cholesterol uptake into intestinal Caco-2 cells.
AB  - Pancreatic secretion is required for efficient cholesterol absorption by the
      intestine, but the factors responsible for this effect have not been clearly
      defined. To identify factors involved and to investigate their role in
      cholesterol uptake, we studied the effect of Viokase(R), a porcine pancreatic
      extract, on cholesterol uptake into human intestinal Caco-2 cells. Viokase is
      capable of facilitating cholesterol uptake into these cells such that the level
      of uptake is 5-fold higher in the presence of solubilized Viokase. This
      stimulation is time-dependent and is dependent on the presence of bile salt.
      However, bile salt-stimulated pancreatic cholesterol esterase, which has been
      proposed to mediate cholesterol uptake, is not fully responsible. The major
      cholesterol transport activity was purified and identified as pancreatic
      phospholipase A2. Anti-phospholipase A2 antibodies abolished virtually all of the
      phospholipase A2 and cholesterol transport activity of solubilized Viokase. We
      demonstrate that both phospholipase A2 and cholesterol esterase increase
      cholesterol uptake by hydrolyzing the phosphatidylcholine that is used to prepare
      the cholesterol-containing micelles. In the absence of cholesterol esterase or
      phospholipase A2, uptake of cholesterol from micelles containing
      phosphatidylcholine is not as efficient as uptake from micelles containing
      phospholipase A2-hydrolytic products. These results indicate that phospholipase
      A2 may mediate cholesterol absorption by altering the physical-chemical state of
      cholesterol within the intestine.

PMID- 9148963
TI  - Mitogen-activated protein (MAP) kinase regulates production of tumor necrosis
      factor-alpha and release of arachidonic acid in mast cells. Indications of
      communication between p38 and p42 MAP kinases.
AB  - Aggregation of the high affinity IgE receptor (FcepsilonRI) in a mast cell line
      resulted in activation of the p42 and the stress-activated p38 mitogen-activated
      protein (MAP) kinases. Selective inhibition of these respective kinases with PD
      098059 and SB 203580 indicated that p42 MAP kinase, but not p38 MAP kinase,
      contributed to the production of the cytokine, tumor necrosis factor-alpha, and
      the release of arachidonic acid in these cells. Neither kinase, however, was
      essential for FcepsilonRI-mediated degranulation or constitutive production of
      tumor growth factor-beta. Studies with SB 203580 and the p38 MAP kinase activator
      anisomycin also revealed that p38 MAP kinase negatively regulated activation of
      p42 MAP kinase and the responses mediated by this kinase.

PMID- 9148962
TI  - Extracellular cleavage of the vascular endothelial growth factor 189-amino acid
      form by urokinase is required for its mitogenic effect.
AB  - Alternative splicing of vascular endothelial growth factor (VEGF) mRNA results in
      three distinct molecular forms of 121 or 165 (V165) amino acids that are released
      in the conditioned medium of cultured cells and one longer isoform of 189 amino
      acids (V189) that remains cell-associated. V189 has been expressed in wild type
      CHO-K1 cells and in glycosaminoglycan-deficient pgsA-745 Chinese hamster ovary
      (CHO) mutant cells. It could be released from CHO-K1 cell membranes by heparin or
      a synthetic peptide designed on the sequence encoded by exon 6 but was freely
      released from CHO mutant cells. In both cases, the immunoreactive V189 was mainly
      released as a 40-kDa cleaved form, provided that the serine protease urokinase,
      but not plasmin, was active. Recombinant V189 was purified from insect cells
      infected with a recombinant baculovirus as a nonmitogenic 50-kDa precursor that
      binds to the receptor Flt-1 but not to Flk-1. It could be matured by urokinase as
      a 38-kDa fragment able to bind to Flk-1 and to trigger cell proliferation. V165
      and V189, however, could be cleaved by plasmin as 34-kDa fragments that exhibit a
      decreased mitogenic activity. These findings indicate that the carboxyl-terminal
      domain of V189 masks its binding domain to Flk-1.

PMID- 9148964
TI  - Specific interactions between ATPase subunits of the 26 S protease.
AB  - The regulatory complex of the 26 S protease contains at least 15 distinct
      subunits. Six of these subunits (S4, S6, S6', S7, S8, and S10b) belong to a novel
      subfamily of presumptive nucleotidases that we call subunit 4 (S4)-like ATPases.
      Each of these putative ATPases was synthesized in reticulocyte lysate containing
      [35S]methionine, and the radiolabeled proteins were used in binding studies. S4,
      S6, S10b, and S6' displayed specific binding to components of the regulatory
      complex separated by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) or two
      dimensional PAGE. S4 bound to S7, and S6 bound two proteins: S8 and centractin, a
      component of the dynactin complex. S10b bound to S6' and bound much more weakly
      to S1 and p50, another component of the dynactin complex. S6' bound to S10b. Two
      subunits, S7 and S8, did not bind any components present on nitrocellulose
      membranes, presumably because S7 and S8 are already oligomeric following
      synthesis. Co-translation and sucrose gradient sedimentation of 35S-labeled
      ATPases demonstrated the formation of S6'-S10b dimers in solution but revealed
      more complex associations, namely the formation of trimers and tetramers, among
      S4, S6, S7, and S8. Progressive COOH-terminal deletions that removed as much as
      300 amino acids from S4 had no effect on the binding of S4 to S7. In striking
      contrast, truncation of 85 NH2-terminal amino acids from S4 abrogated binding,
      clearly implicating the NH2 terminus of S4 in its specific interaction with S7.
      Since S4-like ATPases contain putative coiled-coils within the first 150 NH2
      terminal amino acids, we propose that coiled-coil interactions are responsible
      for the specificity of the observed subunit associations and that these
      associations are important for self-assembly of the regulatory complex.

PMID- 9148965
TI  - Aggregation of the high affinity IgE receptor results in the tyrosine
      phosphorylation of the surface adhesion protein PECAM-1 (CD31).
AB  - One of the earliest events after aggregation of the high affinity receptor for
      IgE (FcepsilonRI) on mast cells is the activation of protein tyrosine kinases
      resulting in tyrosine phosphorylation of numerous proteins. Using a monoclonal
      antibody raised against the rat basophilic leukemia RBL-2H3 cells, we identified
      that platelet/endothelial cell adhesion molecule 1 (PECAM-1 or CD31) was tyrosine
      phosphorylated in these cells. Aggregation of PECAM-1 did not induce a detectable
      increase in its tyrosine phosphorylation, nor did it result in degranulation.
      However, the minimal tyrosine phosphorylation of PECAM-1 in nonstimulated cells
      was dramatically increased after FcepsilonRI aggregation. This receptor-induced
      tyrosine phosphorylation of PECAM-1 was an early event, independent of Ca2+
      influx or of the activation of protein kinase C and of cell adhesion. PECAM-1 is
      an adhesion molecule that is required for the transmigration of leukocytes across
      the endothelium into sites of inflammation. Therefore tyrosine phosphorylation of
      PECAM-1 may modulate its interaction with other molecules, thereby regulating the
      migration of basophils into inflammatory sites.

PMID- 9148966
TI  - The SH3 domain of amphiphysin binds the proline-rich domain of dynamin at a
      single site that defines a new SH3 binding consensus sequence.
AB  - Amphiphysin is an SH3 domain-containing neuronal protein that is highly
      concentrated in nerve terminals where it interacts via its SH3 domain with
      dynamin I, a GTPase implicated in synaptic vesicle endocytosis. We show here that
      the SH3 domain of amphiphysin, but not a mutant SH3 domain, bound with high
      affinity to a single site in the long proline-rich region of human dynamin I,
      that this site was distinct from the binding sites for other SH3 domains, and
      that the mutation of two adjacent amino acids in dynamin I was sufficient to
      abolish binding. The dynamin I sequence critically required for amphiphysin
      binding (PSRPNR) fits in the novel SH3 binding consensus identified for the SH3
      domain of amphiphysin via a combinatorial peptide library approach:
      PXRPXR(H)R(H). Our data demonstrate that the long proline-rich stretch present in
      dynamin I contained multiple SH3 domain binding sites that recognize interacting
      proteins with high specificity.

PMID- 9148967
TI  - The polymyositis-scleroderma autoantigen interacts with the helix-loop-helix
      proteins E12 and E47.
AB  - The basic helix-loop-helix (bHLH) transcription factors E12 and E47 regulate
      cellular differentiation and proliferation in diverse cell types. While looking
      for proteins that bind to E12 and E47 by the yeast interaction trap, we isolated
      the rat (r) homologue of the human (h) polymyositis-scleroderma autoantigen (PM
      Scl), which has been localized to the granular layer of the nucleolus and to
      distinct nucleocytoplasmic foci. The rPM-Scl and hPM-Scl homologues are 96%
      similar and 91% identical. We found that rPM-Scl mRNA expression was regulated by
      growth factor stimulation in cultured rat aortic smooth muscle cells. rPM-Scl
      bound to E12 and E47 but not to Id3, Gax, Myb, OCT-1, or Max. The C terminus of
      rPM-Scl (amino acids 283-353) interacted specifically with a 54-amino acid domain
      in E12 that is distinct from the bHLH domain. Finally, cotransfection of rPM-Scl
      and E47 specifically increased the promoter activity of a luciferase reporter
      construct containing an E box and did not affect the basal activity of the
      reporter construct. rPM-Scl appears to be a novel non-HLH-interacting partner of
      E12/E47 that regulates E2A protein transcription.

PMID- 9148968
TI  - A sequential two-step mechanism for the production of the mature p17:p12 form of
      caspase-3 in vitro.
AB  - The apoptotic cysteine protease, caspase-3, is expressed in cells as an inactive
      32-kDa precursor from which 17 kDa (p17) and 12 kDa (p12) subunits of the mature
      caspase-3 are proteolytically generated during apoptosis. Two amino acid
      sequences, ESMD downward arrowS (amino acids 25-29) and IETD downward arrowS
      (amino acids 172-176), in the precursor have been defined as the cleavage sites
      for the production of the p17 and p12 subunits. Using a cell-free assay system,
      we demonstrate that the caspase-3 precursor appears to be cleaved first at the
      IETD downward arrowS site, producing the p12 subunit and a 20-kDa (p20) peptide.
      Subsequently, the p20 is cleaved at the ESMD downward arrowS site, generating the
      mature p17 subunit. The cleavage at the IETD downward arrowS site required a
      protease activity that was selectively inhibited by the peptide, Ac-IETD-CHO
      (acetyl-IETD-aldehyde), and other protease inhibitors, such as the cowpox viral
      serine protease inhibitor, CrmA, and N-alpha-tosyl-L-phenylalanine chloromethyl
      ketone. The protease that catalyzed the cleavage at the ESMD/S site was
      selectively inhibited by another peptide, Ac-ESMD-CHO (acetyl-ESMD-aldehyde).
      More interestingly, the caspase-3 inhibitor, Ac-DEVD-CHO, but not the caspase-1
      inhibitor, Ac-YVAD-CHO, also selectively inhibited the protease activity that
      cleaves at the ESMD downward arrowS site. This indicated that the cleavage at the
      ESMD downward arrowS site was either autocatalytic or that it required a caspase
      3-like activity. In summary, we demonstrate that production of the p17:p12 form
      of caspase-3 is a sequential two-step process and appears to require two distinct
      enzymatic activities.

PMID- 9148969
TI  - Lactacystin and clasto-lactacystin beta-lactone modify multiple proteasome beta
      subunits and inhibit intracellular protein degradation and major
      histocompatibility complex class I antigen presentation.
AB  - The antibiotic lactacystin was reported to covalently modify beta-subunit X of
      the mammalian 20 S proteasome and inhibit several of its peptidase activities.
      However, we demonstrate that [3H]lactacystin treatment modifies all the
      proteasome's catalytic beta-subunits. Lactacystin and its more potent derivative
      beta-lactone irreversibly inhibit protein breakdown and the chymotryptic,
      tryptic, and peptidylglutamyl activities of purified 20 S and 26 S particles,
      although at different rates. Exposure to these agents for 1 to 2 h reduced the
      degradation of short- and long-lived proteins in four different mammalian cell
      lines. Unlike peptide aldehyde inhibitors, lactacystin and the beta-lactone do
      not inhibit lysosomal degradation of an endocytosed protein. These agents block
      class I antigen presentation of a model protein, ovalbumin (synthesized
      endogenously or loaded exogenously), but do not affect presentation of the
      peptide epitope SIINFEKL, which does not require proteolysis for presentation.
      Generation of most peptides required for formation of stable class I heterodimers
      is also inhibited. Because these agents inhibited protein breakdown and antigen
      presentation similarly in interferon-gamma-treated cells (where proteasomes
      contain LMP2 and LMP7 subunits in place of X and Y), all beta-subunits must be
      affected similarly. These findings confirm our prior conclusions that proteasomes
      catalyze the bulk of protein breakdown in mammalian cells and generate the
      majority of class I-bound epitopes for immune recognition.

PMID- 9148970
TI  - Intracellular association between UDP-glucose:glycoprotein glucosyltransferase
      and an incompletely folded variant of alpha1-antitrypsin.
AB  - Genetic variants of human alpha1-antitrypsin unable to fold into the native
      structural conformation are poorly secreted from hepatocytes. The molecular
      chaperone calnexin coimmunoprecipitates with secretion-incompetent variant
      null(Hong Kong) retained in stably transfected mouse hepatoma cells (Le, A.,
      Steiner, J. L., Ferrell, G. A., Shaker, J. F., and Sifers, R. N. (1994) J. Biol.
      Chem. 269, 7514-7519). Mobilization of intracellular Ca2+ stores with metabolic
      poisons diminished interaction with calnexin and coincided with
      coimmuoprecipitation of a 150-kDa protein (p150). Mobilization of endoplasmic
      reticulum lumenal Ca2+ with thapsigargin, an inhibitor of the microsomal
      Ca2+ATPase, gave a similar result. Coimmunoprecipitation of p150 was specifically
      disrupted in response to incubation of the cell lysate with exogenous CaCl2.
      Finally, in ECL Western blotting, p150 was recognized by polyclonal antiserum
      against UDP-glucose:glycoprotein glucosyltransferase that likely functions in
      glycoprotein folding and quality control (Sousa, M. C., Ferrero-Garcia, M. A.,
      and Parodi, A. J. (1992) Biochemistry 31, 97-105). The data are consistent with a
      model in which perturbation of endoplasmic reticulum Ca2+ results in a stable
      physical association between unfolded human alpha1-antitrypsin and UDP
      glucose:glycoprotein glucosyltransferase.

PMID- 9148971
TI  - Peroxisome proliferators activate extracellular signal-regulated kinases in
      immortalized mouse liver cells.
AB  - Peroxisome proliferators (PPs) are a class of nongenotoxic carcinogens in the
      rodent liver. The induction of immediate-early gene expression in immortalized
      mouse liver cells by the PPs Wy-14, 643, monoethylhexyl phthalate, ciprofibrate
      ethyl ester, and clofibrate suggested that they may be activating growth
      regulatory signal transduction pathways. We report that incubation of quiescent
      ML457 cells with Wy-14,643 resulted in the appearance of two tyrosine
      phosphorylated bands of approximately 44 and 42 kDa with maximal phosphorylation
      at 20 min. These two proteins were identified as extracellular signal-regulated
      kinases (ERKs) ERK1 and ERK2 (also known as mitogen-activated protein kinases, or
      MAPKs). Stimulation of quiescent ML457 cells with monoethylhexyl phthalate,
      ciprofibrate ethyl ester, and clofibrate also resulted in tyrosine
      phosphorylation of ERK1 and ERK2; however, the steroid PP dehydroepiandrosterone
      sulfate, which does not induce immediate-early gene expression, did not induce
      phosphorylation of ERK1 and ERK2. Kinase activity of ERK1 and ERK2 was stimulated
      by the PPs, consistent with their phosphorylation. The PPs also induced
      phosphorylation of the upstream regulator MAPK/ERK kinase (MEK). Preincubation of
      quiescent cells with MEK inhibitor PD98059 blocked activation of ERK1 and ERK2 by
      the PPs, implicating MEK activation as a requirement for PP-induced ERK
      activation. In addition, pretreatment with PD98059 greatly reduced the PP-induced
      expression of immediate-early genes c-fos, egr-1, and to a lesser extent junB.
      Induction of ERK phosphorylation and junB expression by Wy-14,643 was also seen
      in rat hepatocytes. These results attribute many of the effects of PPs on
      immediate-early gene expression to the activation of the MEK/ERK signal
      transduction pathway and add the PPs to the growing number of tumor promoters
      that modulate signaling proteins.

PMID- 9148972
TI  - Creatine phosphokinase elevation in patients presenting to the emergency
      department with cocaine-related complaints.
AB  - The incidence of creatine phosphokinase (CPK) elevation was evaluated in patients
      presenting to an urban emergency department with any complaint related to cocaine
      use within the preceeding 24 hours. Patients with obvious causes of CPK elevation
      (ie, seizure) were excluded. Forty patients were enrolled. CPK values were
      elevated in 21 patients (53%). The mean CPK value for patients with an elevated
      CPK was 1,071 IU/L. There was no statistically significant difference between the
      patient's initial complaint (muculoskeletal, psychiatric, or cardiovascular) and
      the incidence of CPK elevation (P = .35). Thirty of the 40 patients admitted to
      using some other drug(s) in addition to cocaine in the preceding 24 hours. Some
      degree of skeletal muscle injury and CPK elevation appears to be common in
      patients using cocaine.

PMID- 9148973
TI  - Hematocrit as a predictor of significant injury after penetrating trauma.
AB  - A study was undertaken to determine if there are differences in hematocrit (HCT)
      during the initial evaluation of patients with and without significant visceral
      intrathoracic or intraabdominal injury after penetrating trauma and, if so, the
      predictive value of this parameter. Sixty consecutive adults with potentially
      significant penetrating trauma who presented to an urban municipal trauma center
      during a 10-week period were studied. Diagnostic variables were recorded for all
      patients at risk for significant injury, defined as intrathoracic or
      intraabdominal injury requiring surgical intervention. Patients were ultimately
      grouped on the basis of operative findings or observation to discharge. Acquired
      variables included vital signs, initial HCT (HCT-0), HCT at 15 minutes (HCT-15),
      HCT at 30 minutes (HCT-30), and fluid administered. Twenty-one patients had
      significant injuries (INJ), and 39 did not (NO-INJ). INJ patients had lower HCT
      values than NO-INJ on presentation (35% +/- 6% and 41% +/- 5%, respectively). At
      presentation, a low HCT was predictive of significant injury, but a normal HCT
      did not preclude injury. The changes in HCT from arrival to 15 minutes, between
      INJ and NO-INJ patients, were similar (-1.5% +/- 3% and -0.6% +/- 3%
      respectively). Only when the decrease in HCT was > or =6.5% from presentation
      measurements was it predictive of injury. During the first 15 minutes a decrease
      in HCT of > or =6.5% had a positive predictive value and specificity of 1.0. The
      change in HCT between 15 and 30 minutes was less useful. There was a large
      difference between the amounts of fluid given to injured and uninjured patients,
      which may have been responsible for some of the differences in HCT between the
      two groups. These results show that HCT may have some diagnostic utility during
      the early management of penetrating trauma. Presentation with an HCT below
      normal, or an early decrease in HCT, is an indicator of potential injury.
      Although many patients with serious internal injuries do not manifest large
      decreases early after presentation, those who do have a high probability of
      internal injury. The lower the HCT, or the greater the decrease, the greater the
      probability that a significant injury exists.

PMID- 9148974
TI  - Use of physician extenders and fast tracks in United States emergency
      departments.
AB  - To describe current practice regarding the use of physician extenders (PEs) and
      the "fast track" (FT) concept in United States emergency departments (EDs), a
      telephone survey of 250 US health care facilities offering emergency services was
      conducted. Of the EDs surveyed, 21.6% were using PEs at the time of the survey,
      and of those not using PEs, 23.5% intended to do so within the next 2 years.
      Those using PEs had been using them for a mean duration of 3.5 years (the mode
      was 2 years). The mean number of hours of PE coverage was 11.4 hours on weekdays
      and 11.5 hours on weekends (the mode was 12 hours both on weekdays and weekends).
      In general, the use of PEs increased with increasing hospital size and ED census,
      in more urban settings, in teaching facilities, and in the Northeast region of
      the country. Thirty percent of EDs surveyed had FT, and of those that did not
      have FT at the time of the survey, 32.8% intended to institute FT within 2 years.
      Of those that had FT, the mean number of years in use was 2.4 (the mode was 2).
      The use of FT increased with increasing hospital size and ED census, in teaching
      hospitals, and in the Northeast region. FT was most common in the suburban
      setting. The mean estimated percentage of ED patients going through FT was 30.1%.
      The mean number of hours per day of FT operation was 13.4 hours on weekdays and
      13.7 hours on weekends (the mode was 12 hours/day both on weekdays and weekends).
      Of hospitals using PEs in the ED, 56.0% had FT; of hospitals without PEs in the
      ED, 23.5% had FT.

PMID- 9148975
TI  - Photograph documentation of motor vehicle damage by EMTs at the scene: a
      prospective multicenter study in the United States.
AB  - The purpose of this study was to determine if emergency medical service (EMS)
      personnel could take instant photographs of motor vehicle damage at crash scenes
      depicting the area and severity of damage of the crash under adverse weather
      conditions, in different lighting, and quickly enough so as not to interfere with
      patient care. This prospective multicenter trial involved 35 ambulances
      responding to motor vehicle crash scenes in rural, suburban, and urban areas in
      five centers in four states. Emergency medical technicians (EMTs) reported their
      experience implementing a protocol for use of an instant camera to photograph
      vehicle damage at crash scenes. Time reported by EMTs to take the photographs was
      1 minute or less in 204 of 288 (70.9%) of motor vehicle crashes and 2 minutes or
      longer in 12 of 288 (4.2%) of motor vehicle crashes. From one EMS agency in the
      study, 48 scene times during which photographs were taken were, on average, 1.5
      minutes shorter than 48 scene times immediately before implementation of on-scene
      crash photography. Photographs were taken in different weather and lighting
      conditions. EMTs reported they were able to determine both area and severity of
      damage in 260 of 290 (92.5%) crash photographs, but they were unable to determine
      area and severity of damage in only 2 of 290 (0.7%) crash photographs.

PMID- 9148977
TI  - Computed tomography in the emergency department.
AB  - A study was conducted to determine parameters indicating the current use of
      computed tomography (CT) in the emergency department (ED). Computerized data
      regarding patients seen in the ED between 1/1/92 and 9/30/95 were retrieved. A
      rate of 36/1,000 patients underwent CT in the ED (ED CT). Of patients eventually
      hospitalized, 6.04% had ED CT, whereas 2.81% of the discharged patients had
      undergone ED CT (P < .001). The most common region examined by ED CT was the head
      (55.38%), followed by the abdomen (14.19%), pelvis (11.96%), spine (11.46%), and
      chest (5.57%). The hospitalization rates for patients undergoing head and spine
      ED CT were 35.99% and 36.84%, respectively. The hospitalization rates for
      patients undergoing abdomen, pelvis, and chest ED CT were 50.76%, 51.46%, and
      55.61%, respectively. The mean number of patients undergoing ED CT increased
      according to age with a positive linear correlation. Head CT was most common in
      the very young and the very old. Some parameters about the use of ED CT were
      identified. The information obtained will allow comparison of practice between
      EDs in different medical centers and will be useful to hospital administrators,
      health planners, and clinicians. This retrospective analysis is to be followed by
      more comprehensive prospective studies involving different EDs in various
      sections of the country.

PMID- 9148976
TI  - Non-life-threatening blunt chest trauma: appropriate investigation and treatment.
AB  - Non-life-threatening blunt chest trauma is a commonly occurring phenomenon. No
      clear guidelines exist in the literature regarding the appropriate investigation
      and treatment, and most clinicians' practice patterns are based on anecdote,
      individual experience, and the theoretical risk of complications. A prospective
      study was undertaken of all patients with non-life-threatening blunt chest trauma
      presenting to a high-volume, community-based teaching hospital emergency
      department. No clinical features were found to have a high enough positive
      predictive value for rib fracture or any other injury to warrant their use as a
      screening tool for further investigations. No significant lung injury was
      detected in the study cohort of patients, on either an immediate or delayed
      basis. In the absence of compelling evidence of an underlying lung injury, the
      performance of chest or rib radiography is of no benefit, and considerable cost
      savings can potentially be realized.

PMID- 9148978
TI  - Seroprevalence of hepatitis B and hepatitis C among rural emergency medical care
      personnel.
AB  - To identify the prevalence of serologic markers of hepatitis B and hepatitis C
      among rural prehospital providers, a prospective descriptive study was conducted
      of a rural county emergency medical services (EMS) system. Participants included
      107 prehospital care providers: 102 EMT-Bs, 1 paramedic, and 4 law enforcement
      first responders. Blood samples taken from prehospital care providers were tested
      for hepatitis B surface antigen (HBsAg), antibody to HBsAg (HBsAb), antibody to
      hepatitis B core antigen (HBcAb), and antibody to hepatitis C (anti-HC). The 107
      providers had a total of 635 years of EMS experience (5.93 years per subject).
      Three providers (3%) had received previous blood transfusions, 7 (7%) had worked
      in a metropolitan area, and 6 (6%) had multiple sexual partners prior to the
      study. No provider reported intravenous drug use or known homosexual or bisexual
      contact. Only one sample tested positive for hepatitis C antibody (anti-HC) and
      hepatitis surface antibody (HBsAb). Rural prehospital care personnel have a low
      prevalence (0.9%) of exposure to hepatitis B and hepatitis C. Despite this fact,
      continued vigilance should be maintained in preventing transmission of bloodborne
      illnesses.

PMID- 9148979
TI  - Sternal fractures in blunt chest trauma: a practical algorithm for management.
AB  - A retrospective review of the medical records of blunt trauma patients with
      sternal fracture admitted to a level 1 trauma center from June 1990 to June 1993
      was undertaken to determine the relationship between sternal fractures and
      clinically significant myocardial injury, and to assess the usefulness of cardiac
      evaluation and monitoring in these patients. Of 33 patients with sternal
      fracture, 31 were in motor vehicle crashes and 2 were pedestrians struck. All had
      Glasgow Coma Scale score = 15. No patient had a severe, life-threatening,
      associated injury (Abbreviated Injury Score of >3). No electrocardiogram or
      echocardiogram showed evidence of acute injury or ischemia. No arrhythmias
      requiring treatment were noted. No CPK-MB fraction was >5%. These results show
      that sternal fracture is not a marker for clinically significant myocardial
      injury. The management of sternal fracture patients should be directed toward the
      treatment of associated injuries.

PMID- 9148980
TI  - Cervical prevertebral soft-tissue measurements and chest radiographic findings in
      acute traumatic aortic injury.
AB  - Acute traumatic aortic injury (ATAI) results in several characteristic chest
      radiographic findings, most notably mediastinal widening. This study was based on
      the hypothesis that blood or fluid in the widened mediastinum might track up into
      the neck and be detected on lateral cervical radiographs. In a blinded,
      retrospective, case-control review of radiology files, 13 consecutive adult cases
      of ATAI were identified and compared with 19 cases of negative aortography (NAO)
      and 18 multiple trauma victims (MT) without aortography. Cases with inadequate
      cervical films or cervical injury were excluded. Measurements included the
      cervical soft-tissue (ST) width at the third (C3) and sixth (C6) cervical
      vertebrae, mediastinal width, mediastinal-chest width ratio, and the presence of
      several characteristic chest radiograph findings of ATAI. The C3 ST measurements
      averaged 9.1 +/- 2.8 mm, 8.5 +/- 2.7 mm, and 6.9 +/- 2.2 mm for the ATAI, NAO,
      and MT groups, respectively. The C6 ST measurements averaged 19.2 +/- 4.5 mm,
      18.6 +/- 3.9, and 16.5 +/- 3.8 mm for the ATAI, NAO, and MT groups, respectively.
      These cervical ST values were not significantly different between groups at
      either C3 (P = .188) or C6 (P = .148). The incidence of abnormal ST swelling of
      >7 mm at C3 was 38%, 53%, and 33% for the ATAI, NAO, and MT groups, respectively.
      The incidence of abnormal ST swelling of >20 mm at C6 was 54%, 42%, and 11% for
      the ATAI, NAO, and MT groups, respectively. Cervical ST measurements at C3 or at
      C6 did not correlate with mediastinal-chest width ratios. Mediastinal widening,
      aortopulmonic window opacification, and blurring of the aortic knob were the most
      sensitive chest radiography findings in ATAI, although each of these lacked
      useful specificity and accuracy. Cervical ST swelling is not a useful marker for
      ATAI.

PMID- 9148981
TI  - Lung hernia.
AB  - Lung hernia is an uncommon entity usually resulting from trauma or inadequate
      healing from recent or remote thoracic surgery. A small percentage may be
      congenital. Four cases are reported, each demonstrating lung herniation resulting
      from either accidental or postsurgical trauma. Most of the previous cases have
      been reviewed in various surgical and radiological journals with only rare
      mention in the emergency medicine literature. Because emergency physicians may be
      the most immediate contact for patients who develop a lung herniation, they
      should be cognizant of this entity as a possible delayed complication to chest
      wall injury. Awareness of the clinical and radiological appearance of lung hernia
      will help to avoid its confusion with other conditions such as subcutaneous
      emphysema, chest tumor, pneumothorax, or a focus of infection.

PMID- 9148982
TI  - Rapid sequence intubation in adults with elevated intracranial pressure: a survey
      of emergency medicine residency programs.
AB  - A questionnaire entitled "Survey of Protocols for Rapid Sequence Intubation in
      Previously Healthy Adults with Elevated Intracranial Pressure" was distributed to
      the program directors of all 100 emergency medicine residency programs listed in
      the Directory of Graduate Medical Education Programs in February 1995. The
      medical literature on rapid sequence intubation in patients with suspected
      intracranial pressure elevations was reviewed. The findings of the review were
      compared with the survey responses. Sixty-seven program directors responded to
      the survey. Sixty-five programs performed rapid sequence intubation in their
      institution. Five programs performed 0 to 10 procedures annually. Six performed
      10 to 30 annually, 19 performed 30 to 50, 17 performed 50 to 100, and 18
      performed more than 100. Succinylcholine and vecuronium were the most frequently
      used neuromuscular blockers. Midazolam and thiopental were the most frequently
      used sedative induction agents. Most programs use a defasciculating agent prior
      to succinylcholine administration. The majority of programs do not use a priming
      agent before the use of a nondepolarizing neuromuscular blocking agent.
      Intravenous lidocaine was routinely administered prior to neuromuscular blockade.
      Fentanyl was the most frequently used other pretreatment medication. Rapid
      sequence intubation is used to facilitate definitive, emergent airway management
      in patients with suspected intracranial pressure elevations in almost all of the
      emergency medicine residency programs that responded to the survey. Most of these
      programs follow the guidelines recommended in the medical literature. The
      majority of these guidelines, however, are based on statistical data performed in
      the laboratory or nonemergency environments. Further clinical studies in an
      emergency medicine environment must be performed to determine the optimal drug
      regimen for rapid sequence intubation in patients with elevated intracranial
      pressure.

PMID- 9148983
TI  - Research funding in the four major emergency medicine journals.
AB  - The objective of this survey was to determine the percentage of unfunded studies
      published in the four major emergency medicine journals and to examine the
      sources in funded studies. This study was a retrospective survey of all issues of
      the four general emergency medicine journals in 1994. Funding was categorized as
      public national, private, international, institutional, or unfunded. The total
      funding and sources were recorded for each of the four journals. Confidence
      intervals (CIs) were determined to compare the percent of funded versus unfunded
      articles. Overall, significantly more of the emergency medicine articles in the
      four journals were unfunded (63% unfunded [95% CI = 56.7-69.1]; 37% funded [95%
      CI = 30.9-43.3]). The sources of funding for each of the journals varied, with
      most being private (45%). In conclusion unfunded research remains a major source
      of emergency medicine literature in the four main emergency medicine journals.

PMID- 9148984
TI  - Pelvic inflammatory disease in patients with bilateral tubal ligation.
AB  - Classic teaching has stated that women who have undergone bilateral tubal
      ligation (BTL) are not susceptible to pelvic inflammatory disease (PID). The
      purpose of this study was to confirm the existence of PID in patients with BTL
      and to compare clinical parameters of these patients with PID patients who have
      not had BTL. A retrospective chart review of emergency department (ED) patients
      diagnosed with PID over a 1-year period at a large urban university hospital
      found 209 patients who fulfilled the criteria for a definition of PID. Of the 209
      patients with PID, 24 (11.7%) had undergone BTL. Patients with and without BTL
      were compared with respect to age, white blood cell count (WBC), temperature,
      admission rate, length of hospitalization, prior history of PID, culture results,
      presence of bilateral abdominal pain, presence of rebound tenderness, and
      complications of tubo-ovarian abscess (TOA) and hydrosalpinx. Patients with BTL
      had lower WBCs (11,100/microL v14,700/microL) and were 2.5 times less likely to
      be hospitalized compared to those patients without BTL. These results show that
      PID in the setting of a prior BTL not only exists but occurs with surprising
      frequency and deserves further study. Patients with BTL and PID may have a
      clinically milder form of PID than those patients without BTL.

PMID- 9148985
TI  - Upper torso cyanosis: a marker for blunt cardiac rupture.
AB  - Cardiac rupture is a frequent cause of death following blunt trauma. Most of
      these patients die at the scene with only a few surviving to make it to the
      hospital. With improvements in prehospital care and rapid regional transport,
      more of these patients may arrive at the hospital with signs of life.
      Classically, these patients arrive with the constellation of symptoms that
      characterize cardiac tamponade (hypotension, distended neck veins, and distant
      heart sounds). The differential appearance of upper body cyanosis frequently
      accompanies these injuries. Prompt recognition and expeditious surgical treatment
      may increase the number of survivors of this catastrophic injury. Presented here
      is an illustrative case report and review of the literature.

PMID- 9148986
TI  - Incremental analysis of diagnostic peritoneal lavage fluid in adult abdominal
      trauma.
AB  - It is uncertain how much diagnostic peritoneal lavage (DPL) fluid must be
      recovered from abdominal trauma patients to avoid falsely low red blood cell
      (RBC) counts. A study was carried out to investigate this controversy. A
      convenience sample of adult abdominal trauma patients in a Level 1 university
      trauma center who were undergoing DPL with 1 L crystalloid was enrolled. Subjects
      with grossly positive or colorless effluent were excluded. A blinded prospective
      experimental design was used. Differences were evaluated among RBC counts
      collected at 200, 400, 600, and 800 mL of returned fluid using repeated-measures
      analysis of variance. In 11 patients, mean RBC counts collected at 200 and 400 mL
      were 24,600 (95% confidence interval [CI], 20,700 to 29,100) and 39,700 (95% CI,
      33,200 to 47,100) cells/microL. These were substantially lower than the final
      mean count of 95,800 (95% CI, 80,000 to 115,800), measured at 800 mL (F = 23.7, P
      < .0001). Mean counts at 600 mL were less than those obtained at 800 mL but were
      not statistically different (P = .08). Two of the 11 subjects would have been
      misclassified (as not requiring surgery) had "early" sampling been used. In
      abdominal trauma patients, the RBC count of DPL fluid regularly increases as more
      fluid is recovered. It is important to collect >600 mL of effluent to avoid
      misleading, low RBC counts and misclassification of patients.

PMID- 9148987
TI  - Alcoholic ketoacidosis presenting with extreme hypoglycemia.
AB  - A 66-year-old man with a history of chronic alcoholism presented with Kussmaul
      respirations following several days of fasting accompanied by vomiting, in the
      presence of continued ethanol intake. He was subsequently found to have a serum
      glucose level of <20 mg/dL and an anion gap of 36. Despite his profound
      hypoglycemia, he was fully alert with no obvious neurological deficits. He
      recovered without incident with intravenous saline, dextrose, thiamine, and
      antibiotics for a bacteremic pneumonia. He had no evidence of hypoxemia,
      hypotension, or other features of sepsis. Alcoholic ketoacidosis in the setting
      of hypoglycemia is discussed. If the serum glucose level is less than the anion
      gap, the diagnosis of alcoholic ketoacidosis should be considered.

PMID- 9148988
TI  - An unusual case of mesenteric ischemia in a patient with new-onset diabetes
      mellitus.
AB  - The early detection of acute mesenteric ischemia is crucial for the preservation
      of bowel viability. The emergency physician must have a high index of suspicion
      to identify mesenteric ischemia when there is a paucity of physical examination
      findings. We discuss the case of a patient who presented to the emergency
      department with confusion, hyperglycemia, abdominal tenderness, and metabolic
      acidosis who also developed mesenteric ischemia.

PMID- 9148989
TI  - Informed consent and parental choice of anesthesia and sedation for the repair of
      small lacerations in children.
AB  - This study investigated the issue of informed consent by surveying parent
      preferences for local anesthesia and sedation in the repair of small lacerations
      in their children in the emergency department (ED). Of the 45 ED patients with
      actual lacerations receiving a suture repair, 11 requested tetracaine-adrenaline
      cocaine (TAC), 25 requested infiltrated lidocaine, and 9 were not given a choice
      (lidocaine administered because of wound proximity to a mucous membrane site).
      All 45 patients preferred nonsedation over sedation. In 44 of 45 patient cases,
      parents preferred to be included in the medical decision-making for their
      children. Of the 94 non-ED cases (interviewed in private offices) with a
      hypothetical chin laceration, 16 preferred TAC and 78 preferred infiltrated
      lidocaine. Sixty-seven of 94 preferred nonsedation over sedation. In 89 of 94
      patient cases, parents preferred to be included in the medical decision-making
      for their children. Favorable points of continuous informed consent were
      presented, with risks, benefits, and alternatives disclosed. From the data
      presented, the following conclusions were drawn: (1) parents preferred
      infiltrated local anesthesia more commonly than topical local anesthesia; (2)
      parents preferred nonsedation over sedation under the clinical circumstances
      described; (3) parents overwhelmingly preferred to be included in the medical
      decisions affecting their children.

PMID- 9148990
TI  - Diagnostic evaluation for infectious etiology of sickle cell pain crisis.
AB  - Occult infections during sickle cell pain crisis can be associated with
      significant morbidity. It has been suggested that empiric workup for pneumonia
      and urinary tract infection (UTI) is required. A study was undertaken to
      determine whether clinical criteria can be used to exclude such infections as
      precipitants of pain crisis in adults. This retrospective, observational clinical
      study was conducted in an inner-city teaching hospital emergency department (ED)
      with 95,000 visits/year. Patients 18 years of age or older presenting to the ED
      with sickle cell pain crisis who had not used antipyretics within 6 hours before
      presentation were eligible. Ninety-four visits were evaluated. During initial
      evaluation the treating physician completed a questionnaire addressing systemic,
      pulmonary, and urinary tract signs and symptoms. Temperature and physical
      examination were recorded on an ED memo. Treatment modalities were at the
      discretion of the treating physician. All patients had a complete blood count,
      reticulocyte count, urinalysis, and chest radiograph. If the urinalysis was
      positive (>2 white blood cells) or the patient had clinical evidence of a UTI, a
      urine culture was obtained. UTI was confirmed through a urine culture with
      >100,000 colony-forming units/mL. Chest X-rays were reviewed by a staff
      radiologist. Definitive diagnosis of pneumonia was made by the presence of an
      infiltrate and a positive clinical response to antibiotic therapy. Thirty-eight
      patients totalling 94 visits to the ED were studied during an 18-month period.
      Six diagnoses of pneumonia and 3 diagnoses of UTI were made. All six patients
      with pneumonia had at least 4 of the signs and symptoms including fever, chills,
      cough, shortness of breath, sputum production, chest pain, hemoptysis, abnormal
      pulmonary examination, and temperature of >37.8 degrees C. Of the three patients
      with UTI, two had signs and symptoms inconsistent with UTI (asymptomatic
      bacteriuria). In patients with sickle cell pain crisis, medical history and
      physical examination can be useful to predict the absence of pneumonia, but may
      not be as beneficial in predicting the absence of UTI. These results suggest that
      empiric chest x-ray may be unnecessary to exclude pneumonia; however, routine
      urinalysis may be indicated. Because of the low incidence of these infections,
      larger studies are required to confirm these findings.

PMID- 9148991
TI  - Stool appearance in intussusception: assessing the value of the term "currant
      jelly".
AB  - This study surveyed the stool appearance descriptions of 107 inpatient children
      with intussusception. Fifty-six patients presented with grossly bloody stools
      (passed spontaneously), 10 of which were determined on chart review to resemble
      currant jelly. Of the 51 patients without grossly bloody spontaneously passed
      stools, 35 patients had rectal examination results charted. Eight of these
      children had grossly bloody stools noted on rectal examination, 4 of which were
      determined on chart review to resemble currant jelly. While most of the grossly
      bloody stools were not consistent with pure currant jelly, the most common terms
      used in describing the grossly bloody stools were "bloody," "mucus," "red," and
      "diarrhea." Since stools truly resembling currant jelly account for a minority of
      the grossly bloody stools in intussusception, the term "currant jelly stools"
      should be assessed in the teaching of intussusception. Generic terms such as
      blood, mucus, burgundy, red, etc, are more objective and sensitive at identifying
      cases of intussusception. Junior physicians who are taught the classic
      presentation of intussusception with currant jelly stool should also be taught
      that intussusception should be considered in the differential diagnosis of
      children passing any type of bloody stool. As a result, physicians with limited
      experience will be more likely to appropriately consider the diagnosis of
      intussusception, permitting a more timely diagnosis and a better outcome.

PMID- 9148992
TI  - Neonatal fever: utility of the Rochester criteria in determining low risk for
      serious bacterial infections.
AB  - The purpose of this study was to test the utility of the Rochester criteria in
      determining which febrile neonates are at low risk for serious bacterial
      infections (SBI). This was a retrospective study over a 5-year period of 134
      patients younger than 29 days old with fever without a source evaluated in the
      emergency department. Results of urinalysis, lumbar puncture, peripheral white
      blood cell count, and cultures of blood, urine, cerebrospinal fluid, and stool
      were recorded. Of the 134 neonates, 71 were high-risk, 48 low-risk, and 15 were
      not classifiable by the available data. Nineteen of the 71 high-risk patients
      (26.8%) had SBI (2 patients had 2 SBI). Three of the 48 low-risk neonates (6.3%)
      had SBI (1 patient had 2 SBI). None of the 15 nonclassifiable patients had SBI.
      Employing the Rochester criteria to the fully cultured neonates who could be risk
      stratified, the sensitivity, specificity, positive predictive value, and negative
      predictive value were 86.4%, 46.4%, 26.8%, and 93.8%, respectively. Although
      outpatient management of febrile neonates may be feasible, a small percentage of
      neonates meeting low-risk criteria will have a SBI.

PMID- 9148993
TI  - Evaluation of the cardiac STATus CK-MB/myoglobin card test to diagnose acute
      myocardial infarctions in the ED.
AB  - A study was undertaken to evaluate a Card Test called "Spectral Diagnostics Inc
      Cardiac STATus CK-MB/Myoglobin" (Toronto, Canada), which is distributed by Dade
      International Inc, Miami, FL, for the simultaneous qualitative determination of
      CK-MB and myoglobin levels in human serum. The Card Test is advertised by the
      manufacturer as an aid in diagnosing acute myocardial infarction (AMI) in the
      emergency department (ED). Fifty-eight consecutive serum samples were obtained
      from 25 patients being evaluated for AMI in an ED. Qualitative CK-MB and
      myoglobin results from the Card Test were compared with quantitative CK-MB and
      myoglobin results using the ACS-180 instrument (Ciba Corning Diagnostics,
      Medfield, MA) and Stratus IIntellect T (Dade International Inc, Miami, FL),
      respectively. Qualitative results from the STATus CK-MB/Myoglobin Card Test were
      similar, diagnostically, to quantified results using these automated instruments.

PMID- 9148994
TI  - Acute lingual tonsillitis.
AB  - A 45-year-old woman presented to the emergency department (ED) with a 3-day
      history of fever, progressive sore throat, dysphagia, and difficulty speaking.
      She was diagnosed with acute lingual tonsillitis. The ED physician must consider
      this rarely discussed disorder when presented with the previously mentioned signs
      and symptoms. This will allow for prompt diagnosis and treatment of acute lingual
      tonsillitis and may help to avoid potential airway compromise.

PMID- 9148995
TI  - Right pneumothorax with the S1Q3T3 electrocardiogram pattern usually associated
      with pulmonary embolus.
AB  - An 18-year-old man presented with a spontaneous right pneumothorax. An initial
      electrocardiogram (ECG) showed an S wave in lead I, a Q wave in lead III, and an
      inverted T wave in lead III. This ECG pattern, S1Q3T3, has been most often
      associated with pulmonary embolus. These changes resolved with partial
      reexpansion of the lung. Both right and left pneumothorax have been associated
      with ECG changes, including changes that mimic myocardial ischemia. Because the
      clinical presentation of pneumothorax may be similar to angina or pulmonary
      embolus, ECG changes with pneumothorax may lead to confusion in the diagnosis.

PMID- 9148996
TI  - Cases in electrocardiography.

PMID- 9148997
TI  - The sky is a limit: errors in prehospital diagnosis by flight physicians.
AB  - The medical records and air evacuation reports of 186 trauma patients were
      examined to determine the type and characteristics of missed diagnoses. More than
      35% of all cases of hypovolemic shock were not identified, nor were two cases of
      respiratory distress. Although unconsciousness was always identified correctly,
      almost 7% of all cases with partial unconsciousness were not recorded. Of 443
      diagnoses, 337 were correctly recorded by the flight physician, slightly more
      than 76%. The flight physicians missed 10 critical diagnoses, all of which were
      feasible, 56 important diagnoses, 42 of which were feasible, and 40 relatively
      marginal diagnoses, 27 of which were feasible. Injuries to the head, face, and
      limbs were usually diagnosed correctly, and were missed only in a few cases. Of
      considerable clinical relevance was the observation that flight physicians missed
      a significant number of critical and important feasible diagnoses of five types:
      (1) more than half of all feasible diagnoses in the eyes; (2) a third of feasible
      diagnoses of cervical spine injuries; and a significant percentage of injuries to
      the (3) abdomen, (4) chest, and (5) pelvis. Blunt diagnoses were missed more
      often than penetrating injuries. Feasible diagnoses were missed in two of the
      four cases of paralysis, approximately one third of all crush injuries, and one
      quarter of all fractures. This study illuminates preventable errors of physicians
      during air evacuation and indicates particular types of serious, feasible
      diagnoses that flight physicians are prone to miss. Medicine in the sky may pose
      limits to our diagnostic abilities but the limits could be pushed further.

PMID- 9148998
TI  - Ethics and clinical emergency medicine practice.

PMID- 9148999
TI  - Intramural hematoma of the esophagus: ED diagnosis and treatment.

PMID- 9149000
TI  - Pasteurella multocida as a cause of acute adult epiglottitis.

PMID- 9149001
TI  - Bilateral hyphemas as a result of air bag deployment.

PMID- 9149002
TI  - Translaryngeal guided intubation in the airway of a patient with acute
      gastrointestinal hemorrhage.

PMID- 9149003
TI  - Variations in ED census and day of the week.

PMID- 9149004
TI  - Analgesic prescriptions for ED patients with pelvic or dental pain.

PMID- 9149005
TI  - Refractory Raynaud's phenomenon in scleroderma: an indication for surgery.

PMID- 9149006
TI  - Subungual splinter removal.

PMID- 9149007
TI  - Topical epinephrine therapy of acute uvulitis.

PMID- 9149008
TI  - Oscar Auerbach, M.D.: in memoriam.

PMID- 9149009
TI  - Use of primary breast carcinoma characteristics to predict lymph node metastases.

PMID- 9149010
TI  - Diffuse pagetoid squamous cell carcinoma in situ of the esophagus: a case report.
AB  - BACKGROUND: In Western countries, esophageal squamous cell carcinoma is usually
      advanced at presentation and is rarely diagnosed in situ. The authors studied an
      in situ squamous cell carcinoma that occupied the entire mucosa of a 9 cm length
      of esophagus, causing dysphagia for solid food in a woman aged 68 years. METHODS:
      The esophagectomy specimen contained a circumferential region of depressed tan
      mucosa in the middle and lower thirds, bordered above and below by normal
      squamous mucosa, without ulcer, stricture, or mass. The entire lesion was
      submitted for histology and evaluated with immunostains for cytokeratins and
      markers of Paget's cells, p53 mutation, and proliferation. RESULTS: The lesion
      involved 45 cm2 of mucosa. Large, atypical cells with frequent mitoses occupied
      the basal layers of the squamous epithelium and were often separated from more
      superficial maturing cells by acantholysis. Pagetoid spread of tumor cells into
      nonneoplastic surface and gland duct epithelium was prominent. The tumor cells
      expressed cytokeratins of low molecular weight, p53 gene product, and
      proliferating cell nuclear antigen (PCNA), but lacked markers usually seen in
      Paget's cells in the breast or vulva. No invasion was evident. CONCLUSIONS: This
      extensive in situ squamous cell carcinoma of the esophagus resulted from pagetoid
      spread of tumor cells. These cells had a phenotype suggestive of origin from
      primitive epidermal stem cells and also had overexpressed p53 and PCNA, but they
      lacked the capacity to penetrate the basement membrane. Flat, erythematous areas
      of esophageal mucosa seen during endoscopy could represent early squamous cell
      carcinoma and should be biopsied.

PMID- 9149011
TI  - Basaloid squamous cell carcinoma of the esophagus: diagnosis and prognosis.
AB  - BACKGROUND: Basaloid squamous cell carcinoma (BSCC) is a recently recognized,
      poorly differentiated variant of squamous cell carcinoma (SCC), which is located
      predominantly in the upper aerodigestive tract. METHODS: In this study, clinical
      and pathologic parameters of 17 BSCCs and 133 typical SCCs of the esophagus that
      underwent potentially curative resection (no distant metastases, no residual
      tumor) were compared. In addition, light microscopic, electron microscopic, and
      immunohistochemical features of BSCC were investigated, to determine whether this
      type of carcinoma could be differentiated from other poorly differentiated
      carcinomas of the esophagus. RESULTS: Light microscopic study showed that BSCC
      was composed of relatively small tumor cells, arranged in solid lobules with
      abundant comedo-type necrosis. BSCC was almost invariably accompanied by areas of
      concomitant typical SCC, foci of squamous cell differentiation, and/or severe
      squamous cell dysplasia or carcinoma in situ of the adjacent mucosa.
      Ultrastructurally, BSCC inconsistently showed features of squamous cell
      differentiation. Immunohistochemically, BSCC displayed poor reactivity for
      antibodies against wide-range cytokeratins and cytokeratin subtypes that are
      typical of squamous cell epithelia (cytokeratin 13 and cytokeratin 14).
      Infrequently, expression of Leu7, smooth muscle actin, and S-100 protein was
      found. In comparison with typical SCC, the characteristic features of BSCC were
      older patient age, higher proliferative activity (MIB-1 labelling index), and
      higher apoptotic indices. No differences were found with regard to pT
      classification, pN classification, tumor size, blood vessel invasion, lymphatic
      vessel invasion, neural invasion, or patient gender. Moreover, no differences in
      overall survival rates were found. CONCLUSIONS: BSCC is a distinct
      histopathologic variant of SCC, characterized by a poor degree of differentiation
      and high proliferative activity. However, after potentially curative resection,
      the prognosis of patients with BSCC of the esophagus does not differ from that of
      patients with typical SCC.

PMID- 9149012
TI  - Detection of epidermal growth factor receptor in the serum of gastric carcinoma
      patients.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) is overexpressed in various
      malignancies including carcinoma of the breast, lung, esophagus, cervix, and
      stomach. In patients with gastric carcinoma, its overexpression may be associated
      with advanced stage and poor prognosis. METHODS: The levels of EGFR extracellular
      domain were determined in serum from 40 gastric carcinoma patients using enzyme
      linked immunosorbent assay. Serum EGFR levels were measured in 5 Stage I, 2 Stage
      II, 6 Stage III, and 27 Stage IV patients, and 29 healthy controls. RESULTS: The
      mean serum level for EGFR in the gastric carcinoma patients was significantly
      elevated compared with that of healthy controls (681 +/- 226 fmol/mL vs. 440 +/-
      46 fmol/mL; P < 0.0001). Thirty-one patients with gastric carcinoma (77.5%)
      showed elevated EGFR levels above a cutoff value of 532 fmol/mL (defined as 2
      standard deviations above the mean of the controls). No significant association
      was noted between positivity of EGFR and gender, age, stage, and tumor
      differentiation. CONCLUSIONS: The authors believe that serum EGFR could be useful
      as a tumor marker of gastric carcinoma for diagnosis, prognosis, follow-up after
      surgery, and monitoring patient response to chemotherapy.

PMID- 9149013
TI  - Uracil and tegafur modulated with leucovorin: an effective regimen with low
      toxicity for the treatment of colorectal carcinoma in the elderly. Oncopaz
      Cooperative Group.
AB  - BACKGROUND: In spite of the high prevalence of cancer in the elderly, little
      information is available about the efficacy and toxicity of chemotherapy in
      elderly patients. In a previous study, the authors demonstrated that the
      combination of uracil and tegafur (UFT) with leucovorin (LV) was active and well
      tolerated in patients with advanced colorectal carcinoma (ACC). The objective of
      the current study was to determine the efficacy and toxicity of this regimen in
      elderly patients with ACC. METHODS: Thirty-eight unselected patients older than
      70 years (median age, 74 years) with measurable ACC were included. All patients
      were evaluable for toxicity and response. The regimen consisted of intravenous LV
      500 mg/m2 on Day 1, oral LV 15 mg every 12 hours on Days 2-14, and oral UFT 390
      mg/m2 on Days 1-14. Treatment was repeated every 28 days for a minimum of 4
      courses per patient. RESULTS: Two hundred eighty-eight cycles of chemotherapy
      were delivered (median, 7 per patient). Two patients (5%) achieved a complete
      response and 9 (24%) a partial response, for an overall response rate of 29%.
      Toxicity was mild, without dose-limiting myelosuppression. Four patients (10%)
      experienced Grade 3-4 diarrhea, 1 patient had Grade 3-4 nausea/vomiting, and 1
      had Grade 3-4 mucositis. Grade 3-4 toxicity was more frequent among women than
      men (38% vs. 4%, P < 0.05). CONCLUSIONS: Treatment with oral UFT modulated with
      LV is effective, well tolerated, and feasible on an outpatient basis for elderly
      patients with ACC. However, elderly women should be followed closely for the
      early detection of toxicity.

PMID- 9149014
TI  - A novel chemotherapy for advanced hepatocellular carcinoma with tumor thrombosis
      of the main trunk of the portal vein.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) with tumor thrombosis of the main
      trunk of the portal vein (PVTT) has a poor prognosis. This study was designed to
      evaluate the efficacy of arterial infusion chemotherapy for advanced HCC of this
      type. METHODS: Nine patients with HCC were treated by arterial infusion of a
      chemotherapeutic agent via a subcutaneously implanted injection port. One course
      consisted of the daily administration of cisplatin (10 mg for 1 hour on Days 1-5)
      and the subsequent infusion of 5-fluorouracil (250 mg for 5 hours on Days 1-5).
      In principle, patients were to receive four serial courses of chemotherapy.
      RESULTS: The mean course of chemotherapy was 4.6 (range, 2.6-7.6) months. The
      serum total concentrations of alpha-fetoprotein and des-gamma-carboxyprothrombin
      were reduced after chemotherapy in most of the patients. Two patients showed
      complete response (CR) with disappearance of HCC and PVTT after treatment, and
      the other two showed partial response (PR) (response rate [CR + PR/All cases],
      44.4%). The 3-year survival rate was 40%. The mean survival after the therapy was
      14.9 (range, 4.1-48.9) months. The 50% survival was 9.2 months. Adverse reactions
      were tolerable nausea and loss of appetite. CONCLUSIONS: This chemotherapeutic
      regimen achieved favorable results and may be useful in treating patients with
      HCC with tumor thrombosis of the main trunk of the portal vein.

PMID- 9149015
TI  - Combined cisplatin, doxorubicin, and mitomycin for the treatment of advanced
      pleural mesothelioma: a phase II FONICAP trial. Italian Lung Cancer Task Force.
AB  - BACKGROUND: In a previous FONICAP trial, the combination of doxorubicin (D) and
      cisplatin (P) yielded an objective response rate of 25% and a subjective response
      rate of 50% in patients with mesothelioma. In human mesothelioma cell lines,
      mitomycin (M) showed a synergic activity with P and in a recent randomized study,
      the combination of M and P showed slightly superior activity when compared with
      the PD regimen. METHODS: The authors tested the activity and toxicity of a
      combination chemotherapy regimen including P, 60 mg/m2, D, 60 mg/m2, and M, 10
      mg/m2, all by intravenous infusion on Day 1 every 28 days in a Phase II study.
      RESULTS: Twenty-four chemotherapy-naive mesothelioma patients were enrolled in
      the study. Patient characteristics were the following: the median age was 58
      years; the median performance status was 1; there were 6 Stage I patients, 15
      Stage II patients, 2 Stage III patients, and 1 Stage IV patient; and 10 patients
      had previous asbestos exposure. All patients had pretreatment symptoms: 13 had
      chest pain, 9 had pleural effusion, and 7 had dyspnea. A total of 78 cycles of
      chemotherapy were administered. The only significant side effect was
      myelosuppression, with only 9.5% of patients having Grade 4 toxicity. Among 23
      patients evaluable for response, 5 achieved a partial response (20.8%; 95%
      confidence interval, 7.1-42.1%), 9 had stable disease, and 9 had progressive
      disease (including 1 early death). One patient was not evaluable because of
      treatment refusal. A clinical improvement was observed in 7 of 24 patients (29%).
      CONCLUSIONS: The combination of PDM in patients with pleural mesothelioma is
      feasible and moderately active. However, the observed level of activity is
      similar to that obtained with other two-drug regimens.

PMID- 9149016
TI  - Myxoid chondrosarcoma (chordoid sarcoma) of bone: a report of two cases and
      review of the literature.
AB  - BACKGROUND: Chondrosarcoma of bone is a well recognized, relatively common
      clinicopathologic entity. Morphologically distinct soft tissue chordoid sarcoma
      (CS), or extraskeletal myxoid chondrosarcoma, is a relatively rare tumor that has
      generally been documented in extraosseous soft tissues. METHODS: The clinical and
      pathologic features of two patients with biopsy-proven CS from the pathology
      files of the Mayo Clinic and St. Thomas's Hospital were evaluated. Routine
      hematoxylin and eosin-stained slides were reviewed in both cases. Sections from
      both were examined immunohistochemically using the avidin-biotin-peroxidase
      technique and employing commercially available antibodies to the following
      antigens: S-100 protein, cytokeratin (AE1/AE3), epithelial membrane antigen
      (EMA), CD31, and factor VIII. Appropriate positive and negative controls were
      utilized throughout these procedures. Cytogenetic analysis was performed on fresh
      samples obtained from one tumor. Clinical data were obtained from the patients'
      medical records. RESULTS: The two cases of primary CS of bone arose from the
      right distal femur and right scapula, respectively, in 2 men ages 48 and 76
      years, respectively. Morphologically, the tumors were lobulated, multinodular,
      and comprised of a uniform population of rounded to slightly spindled cells.
      Nuclei were hyperchromatic with inconspicuous nucleoli and surrounded by clear,
      vacuolated to eosinophilic cytoplasm. Neoplastic cells were arranged in
      anastomosing chords, strands, and, less often, nests and pseudopapillary
      structures embedded in an abundant, mostly hypovascular, mucinous matrix. Foci of
      hemorrhage and cystic degeneration were present in both tumors. No well developed
      hyaline cartilage or neoplastic osteoid was observed. Immunohistochemically, one
      neoplasm showed focal positivity for S-100 protein but was uniformly negative for
      cytokeratin (AE1/AE3), factor VIII, and CD31. The other tumor showed no
      immunopositivity with cytokeratin, EMA, or S-100 protein. Cytogenetic analysis in
      the latter tumor revealed a nonrandom reciprocal chromosomal translocation,
      t(9;22)(q22-31;q11-12). Both patients developed local recurrences and widespread
      distant metastases. Wide surgical excision was the primary mode of therapy. One
      patient died of tumor. CONCLUSIONS: Skeletal CS is an extraordinarily rare
      neoplasm with a distinct morphology. Although follow-up data were limited to only
      four examples, including two from the literature, the clinical course appears
      worse than that for usual chondrosarcoma of bone. Wide surgical resection appears
      to represent the best mode of therapy. The role of chemotherapy and radiation
      therapy has not been clearly defined.

PMID- 9149017
TI  - The presence of mucosal human papillomavirus in Bowen's disease of the hands.
AB  - BACKGROUND: Bowen's disease (BD) of the genital skin region is generally
      associated with human papillomavirus (HPV) infection. Various molecular analyses
      have identified mainly HPV-16 in the lesions. However, the HPV genotypes
      associated with BD of the hands have not yet been characterized. METHODS: The
      skin specimens of 12 patients with BD of the hands were investigated
      clinicopathologically and immunohistochemically, and the total DNAs extracted
      from the skin were analyzed for the presence of HPV DNA using Southern blot
      hybridization and polymerase chain reaction (PCR) in combination with restriction
      fragment length polymorphisms (RFLP) and direct sequencing analysis of the
      amplified products. In addition, the histologic localization of HPV DNA was
      examined by in situ hybridization in paraffin embedded sections of HPV positive
      patients. RESULTS: In 8 of 12 BD lesions (66.7%), HPV types (HPV-16, -31, -54, 
      58, -61, -62, and -73) were detected by Southern blot hybridization and/or PCR
      with RFLP and direct sequencing analysis. In 6 of 7 HPV positive lesions examined
      (85.7%), the viral genomes were identified by in situ hybridization in the nuclei
      of keratinocytes in the upper stratum malpighii and/or stratum corneum.
      CONCLUSIONS: These results demonstrate that BD of the hands is frequently
      associated with HPV infection. The seven HPV genotypes are known as mucosal
      (genital) HPVs and to the authors' knowledge, this is the first time HPV-31, -54,
      -58, -61, -62, and -73 have been identified in BD lesions. These findings
      strongly suggest that HPVs related to mucosal lesions play an important role in
      the development of BD of the hands.

PMID- 9149018
TI  - Predictors of axillary lymph node metastases in patients with T1 breast
      carcinoma.
AB  - BACKGROUND: Axillary lymph node metastases (ALNM) are the most important
      predictor of survival in patients with T1 breast carcinoma. Due to a relatively
      low incidence of axillary metastasis in tumors < or = 2 cm, the role of axillary
      lymph node dissection for these patients has been questioned. The purpose of this
      study was to determine the association between the incidence of ALNM and 11
      clinical/pathologic factors by univariate and multivariate analysis. METHODS: The
      authors reviewed data from 918 patients with T1 breast carcinoma who underwent
      level I/II axillary dissection between 1979 and July 1995. The association
      between the incidence of ALNM and 11 clinical/pathologic factors (size,
      lymph/vascular invasion, nuclear grade, S-phase, ploidy, palpability, age,
      estrogen receptor status, progesterone receptor status, HER-2/neu, and histology)
      was analyzed by univariate and, when significant, by multivariate analysis.
      RESULTS: Approximately 23% of the 918 patients with T1 breast carcinoma had ALNM.
      Multivariate analysis identified four factors as independent predictors of ALNM:
      lymph/vascular invasion (P < 0.0001), tumor palpability (P < 0.0001), nuclear
      grade (P = 0.0004), and tumor size (P = 0.01). Among the 117 patients with
      nonpalpable, nonhigh grade tumors < or = 1 cm without lymph/vascular invasion,
      the incidence of ALNM was only 3%. However, the 43 patients with T1c tumors with
      all 3 additional risk factors had a 49% incidence of ALNM. CONCLUSIONS: Clinical
      and pathologic features of the primary tumor can be used to estimate the risk of
      ALNM in patients with T1 breast carcinoma. Such a risk assessment might
      facilitate appropriate management. Routine axillary dissection can be omitted in
      patients at minimal risk of ALNM, if the treatment decision is not influenced by
      lymph node status. Axillary lymph node dissection should be performed routinely
      for all patients with lesions > 1 cm. [See editorial counterpoint on pages 1856
      61 and reply to counterpoint on pages 1862-4, this issue.]

PMID- 9149019
TI  - Survival of women ages 40-49 years with breast carcinoma according to method of
      detection.
AB  - BACKGROUND: The value of mammographic screening in reducing breast carcinoma
      mortality among women younger than 50 years continues to be controversial.
      Previous randomized clinical trials have not been definitive because of
      inadequate sample sizes, prolonged screening intervals, questionable
      randomization, and/or cross-contamination between intervention groups. This study
      uses a historical prospective cohort design to examine differences in prognostic
      factors at the time of breast carcinoma diagnosis and differences in overall
      survival among patients ages 40-49 years, according to the method of breast
      carcinoma detection. METHODS: Women (n = 971) ages 40-49 years diagnosed with
      invasive breast carcinoma between 1986 and 1992 were identified by TUMORS (The
      Upper Midwest Oncology Registry Services). Measures of tumor size, lymph node
      status, and overall survival were compared with breast carcinoma patients whose
      tumors were detected by breast self-exam (BSE), clinical breast exam (CBE),
      patient incidental finding (PI), or mammography. RESULTS: Mean tumor size among
      women in the mammography group was smaller than that among women in the BSE, CBE,
      and PI groups (P < 0.002). Tumors detected by mammography were significantly more
      likely to be localized than those detected by other methods (P < 0.0001).
      Patients whose tumors were detected by mammography had significantly better
      survival than patients in the other detection method groups, especially among
      those with smaller tumors (P < 0.0001). This difference persisted even after
      adjustment for lead time bias. CONCLUSIONS: Women ages 40-49 years whose invasive
      breast carcinoma is detected by mammography have significantly smaller tumors,
      more localized disease, and may have a lower risk of mortality than women whose
      tumors are detected by other methods.

PMID- 9149020
TI  - Transitional cell carcinoma of the endometrium and endometrial carcinoma with
      transitional cell differentiation.
AB  - BACKGROUND: Transitional cell carcinoma (TCC) is rare in the female genital
      tract. Although it is most common in the ovary, small series of cases in the
      cervix have been reported, with isolated cases described in the fallopian tube,
      adnexa uteri, and endometrium. METHODS: Eight cases of primary TCC involving the
      endometrium and 1 case of ovarian TCC metastatic to the endometrium were
      retrieved from the files of the Armed Forces Institute of Pathology and the
      University of Texas Southwestern Medical Center. Cases were selected based on the
      presence of endometrial TCC, whether pure or combined with other patterns, and
      regardless of the relative amount. Immunostaining for cytokeratins 7 and 20 was
      performed. RESULTS: Among the 8 women with primary endometrial tumors, the mean
      age was 61.6 years (range, 41-83 years). Uterine bleeding was the presenting
      symptom in 7 women. Macroscopically, the tumors were polypoid, and infiltrated
      the myometrium, although the extent of infiltration varied. Seven endometrial
      tumors showed a papillary component. TCC was always admixed with other patterns
      (predominantly squamous, but also endometrioid, papillary, and serous patterns),
      with the proportion of the TCC component ranging from 5% to 95% (mean, 63.8%).
      TCC was the main invasive pattern observed in all three of the cases that had
      deep myometrial invasion; these cases also had vascular invasion. Seven tumors
      were confined to the uterus; one was metastatic to the ovary. The ovarian TCC
      metastatic to the endometrium had a pure TCC pattern. Five of 7 cases of TCC had
      cytokeratin 7+/20- immunoreactivity; 2 cases were cytokeratin 7-/20-. Treatment
      of primary endometrial tumors was mainly surgical, with adjuvant radiation
      therapy in 4 cases or chemotherapy in 1 case. Survival ranged from 3 months to
      12.9 years (mean, 5.1 years). Of five women for whom follow-up was available,
      three were alive with no evidence of disease, one was alive with a local
      recurrence, and one died of unrelated disease. CONCLUSIONS: TCC is a rare,
      distinct subtype of endometrial carcinoma with morphologic features of urothelial
      differentiation, but retention of a mullerian immunoprofile. While the overall
      prognosis does not appear to be worse than what might be anticipated for the
      stage of tumor present, TCC appears to be the more aggressive histologic subtype
      among the patterns with which it is admixed.

PMID- 9149021
TI  - Progesterone induces apoptosis and up-regulation of p53 expression in human
      ovarian carcinoma cell lines.
AB  - BACKGROUND: Progesterone (PROG) has been shown to reduce the risk of developing
      ovarian carcinoma in postmenopausal women who have undergone estrogen and
      progestogen replacement therapy, and it has been clinically used to treat some
      types of ovarian tumors. It is not yet clear whether or not the antitumor
      activity of progestogen is due to its ability to induce apoptosis in
      precarcinomatous and carcinomatous ovarian cells. The apoptosis-related genes
      p53, bcl-2, and c-myc have important roles in the regulation of programmed cell
      death, and thus may be involved in the process of the suspected PROG-induced
      apoptosis. METHODS: Antiproliferation effects of PROG on 3AO and AO ovarian
      carcinoma cells were determined by 3H-thymidine incorporation. Apoptosis of the
      PROG-treated cells was determined by DNA laddering analysis and was quantitated
      by both nuclear condensation and flow cytometry after cells were stained with
      propidium iodide. Cell cycle analysis was also performed by flow cytometry. The
      expression of p53, bcl-2, and c-myc after 72 hours of PROG treatment was detected
      by Northern blot analysis. RESULTS: In both 3AO and AO cell lines, cells
      proliferation was maximally inhibited by PROG after 72 hours of treatment at 10
      microM concentration. Under the same conditions, more than 50% of PROG-treated
      cells had undergone apoptosis, whereas less than 3% of the cells were apoptotic
      in untreated cell cultures. After exposure to PROG for 72 hours, cells were
      arrested in the G1 phase of the cell cycle, and the levels of p53 mRNA were
      remarkably increased in both cell lines. No changes in expression of bcl-2 or c
      myc were detected. CONCLUSIONS: PROG significantly inhibited cell proliferation
      and induced apoptosis in both of the ovarian carcinoma cell lines tested in this
      study. PROG treatment markedly up-regulated p53 expression in these cells,
      indicating involvement of p53 in PROG-induced apoptosis.

PMID- 9149022
TI  - Prognostic factors in adult granulosa cell tumor of the ovary.
AB  - BACKGROUND: The clinical course of adult granulosa cell tumor of the ovary is
      characterized by indolent growth tending toward late recurrence. A variety of
      clinical and pathologic parameters have previously been evaluated for
      prognostication with inconclusive results. METHODS: The clinical records and
      tumor sections of 70 patients with adult granulosa cell tumors of the ovary were
      reviewed. Patients with recurrent tumors (REC) (n = 19) were compared with
      patients who remained without disease (NED) (n = 51). RESULTS: Significant
      differences in stage and tumor size were noted between the two groups; however,
      after logistic regression analysis, only stage remained statistically
      significant. Pathologic evaluation revealed that Call-Exner bodies occurred more
      frequently in tumors of the NED patients. Cellular atypia and high mitotic rates
      were more frequent in the REC group; however, after logistic regression analysis,
      only atypia remained statistically significant. When early (< 10 years) and late
      recurring tumors (> 10 years) were compared, statistically significant
      differences were again noted: early recurring tumors had fewer Call-Exner bodies,
      higher mitotic rates, and higher degrees of atypia; late recurring tumors were
      similar to tumors in the NED patients. CONCLUSIONS: Tumor stage and, to a lesser
      extent, tumor size are the only clinical parameters of prognostic importance in
      adult granulosa cell tumors. Cellular atypia and, to lesser extents, mitotic rate
      and the absence of Call-Exner bodies are the only significant pathologic
      prognosticators. It is difficult to predict early recurrences and impossible to
      predict late recurrences using these clinical and pathologic parameters.

PMID- 9149023
TI  - High and low risk prostate carcinoma determined by histologic grade and
      proliferative activity.
AB  - BACKGROUND: Histologic grade of differentiation is a strong prognostic factor for
      prostate carcinoma. However, most tumors fall in the intermediate group. Nuclear
      and nucleolar morphometry and analysis of the argyrophilic nucleolar organizer
      regions (AgNORs) were performed to improve prognosis, especially for patients
      with intermediate histologic grade tumors. METHODS: Core needle biopsies from 65
      patients with primary prostate carcinoma at diagnosis were studied. Patients
      received only hormone therapy. Formalin fixed and paraffin embedded sections were
      stained with the method of Ploton. The mean AgNOR count was calculated in 100
      tumor cells for each case. Nuclear and nucleolar areas from 100 cells were
      measured with an automated image analyzer. One-way analysis of variance and uni-
      and multivariate survival analyses were used for statistical evaluation. RESULTS:
      In the whole series, World Health Organization (WHO) tumor grade, nuclear and
      nucleolar areas, and AgNOR counts were correlated with survival time. By
      multivariate analysis, only AgNOR counts retained independent prognostic
      significance. In WHO Grade 2 carcinoma, the 5-year survival rate for patients
      with AgNOR/cell < or = 7.84 was 77%, but was only 12% for those with higher
      counts (P < 0.0001). These survival rates were similar to those obtained when
      patients with WHO Grade 1 carcinoma and Grade 2 carcinoma plus low AgNOR counts
      were compared with patients with Grade 3 carcinoma and Grade 2 carcinoma plus
      high AgNOR counts. In Gleason intermediate Grade 6 and 7 carcinomas, the 5-year
      survival rate for patients with AgNOR/cell < or = 7.84 was 71%, but was only 7%
      for those having higher counts (P = 0.0001). CONCLUSIONS: Nuclear and nucleolar
      areas, as well as AgNOR counts, supplement histologic grading in the prognostic
      assessment of prostate carcinoma in patients receiving only hormone therapy.
      AgNOR count also is a prognostic factor for patients with intermediate grade
      tumors. The combination of histologic grade and proliferative activity allows the
      stratification of patients into low and high risk groups.

PMID- 9149024
TI  - Flutamide withdrawal plus hydrocortisone resulted in clinical complete response
      in a patient with prostate carcinoma.
AB  - BACKGROUND: Combined androgen blockade (CAB) (medical or surgical castration plus
      antiandrogen therapy) is considered by many to be the optimal endocrine maneuver
      for patients with metastatic prostate carcinoma. When progression occurs after
      CAB, the discontinuation of the antiandrogen is recommended. The authors present
      a patient that had a clinical complete response to flutamide withdrawal plus
      hydrocortisone that, at last follow-up, had been maintained for more than 46
      months. METHODS: A 71-year-old man with a positive family history of prostate
      carcinoma presented in 1989 with urinary frequency and a suspicious digital
      rectal examination. He was found to have a poorly differentiated adenocarcinoma
      (Gleason 4+4). He was started on CAB and his prostate specific antigen (PSA)
      concentration declined from 96 ng/mL to the normal range and was maintained for
      the next 24 months. In 1991 his PSA began to rise, and reached 64 ng/mL by 1993.
      The patient was enrolled on a clinical trial that discontinued the flutamide
      administration and hydrocortisone was initiated. RESULTS: Physical examination at
      the time of enrollment was unremarkable. His PSA declined to below the limits of
      detection after this maneuver and at last follow-up had been maintained there for
      more than 46 months. In 1995, the patient underwent a repeat biopsy of the
      prostate and all six tissue cores were negative for carcinoma. At last follow-up
      in December 1996, the patient had no evidence of disease and was being followed
      routinely; however, the authors were continuing treatment with testicular
      suppression (leuprolide) plus hydrocortisone. CONCLUSIONS: The authors believe
      the residual androgens and steroids produced by the adrenal cortex play a
      meaningful role in prostate carcinoma cell proliferation. Based on this case and
      data from trials supporting the activity of flutamide withdrawal plus adrenal
      suppression, it appears reasonable to evaluate prospectively the discontinuation
      of antiandrogen versus antiandrogen withdrawal plus adrenal suppression in
      individuals failing CAB.

PMID- 9149025
TI  - Detection of prostate carcinoma using prostate specific antigen, its density, and
      the density of the transition zone in Japanese men with intermediate serum
      prostate specific antigen concentrations.
AB  - BACKGROUND: This study was undertaken to determine whether the prostate specific
      antigen (PSA) density (PSAD) and PSAD of the transition zone (PSADT) are useful
      in the detection of prostate carcinoma in Japanese men with intermediate levels
      of serum PSA. METHODS: Two hundred and eighty-seven Japanese men with
      intermediate serum PSA levels (2.1 ng/mL to 10 ng/mL) underwent measurement of
      prostate volume by transrectal ultrasound (TRUS) and systematic biopsy under TRUS
      guidance. The volume of the transition zone was also measured by TRUS in 134
      patients. The PSAD and PSADT were determined for each patient, and their
      relationship to prostate carcinoma detection was examined. RESULTS: Prostate
      carcinoma was detected in 30 of 287 patients (10.5%). Although the serum PSA
      levels were similar in patients with benign and malignant prostate disease (P =
      0.541), the prostate volume (P 0.0009) and PSAD (P < 0.0001) differed
      significantly in the two groups; in the patients with prostate carcinoma, the
      prostate volume was smaller, and the PSAD higher, than in the patients with
      benign disease. At the PSAD cutoff value of 0.18 ng/mL/cm3 or greater, the
      sensitivity was 70% and the specificity was 67% for the diagnosis of prostate
      carcinoma. The PSAD was found to be significantly better in the differentiation
      between benign and malignant prostate disease than the serum PSA in the receiver
      operating characteristic analyses (P = 0.045). However, the receiver operating
      characteristic curve for PSAD was not significantly different compared with that
      for PSA in the men with negative digital rectal examination findings. Prostate
      carcinoma was detected in 9.0% (12 of 134) of the patients who underwent PSADT
      determination. Receiver operating characteristic analyses showed that PSADT was
      not superior to PSA in the detection of prostate carcinoma. CONCLUSIONS: In
      Japanese men with intermediate serum PSA concentrations, PSAD offers additional
      information useful in the detection of prostate carcinoma, but PSADT does not.
      Although use of PSAD may decrease the number of unnecessary biopsies, a
      significant number of prostate carcinomas may be overlooked. Therefore, the
      authors recommend that serum PSA levels continue to be used as an indicator for
      biopsy in Japanese men.

PMID- 9149026
TI  - Quality of life and treatment outcomes: prostate carcinoma patients' perspectives
      after prostatectomy or radiation therapy.
AB  - BACKGROUND: Of the estimated 317,000 men in the United States diagnosed with
      prostate carcinoma in 1996, 57% will have localized disease, and their 5-year
      relative survival rate will be 98%. Limited information exists on patient
      reported quality of life (QOL) and the incidence and severity of treatment
      related side effects. The purpose of this study was to identify and compare
      patients' self-reported QOL and treatment side effects 1-5 years after radical
      prostatectomy or radiotherapy. METHODS: Data collection for this cross-sectional
      study included a mailed, self-administered survey with three parts: a demographic
      survey, the Functional Assessment of Cancer Therapy-General (FACT-G), and a newly
      developed Prostate Cancer Treatment Outcome Questionnaire (PCTO-Q). The FACT-G
      measured the effect of prostate carcinoma on overall QOL in the two treatment
      groups. The PCTO-Q assessed the patients' perceptions of the incidence and
      severity of specific changes in bowel, urinary, and sexual functions. The test
      retest reliability of the PCTO-Q in a pilot study was 91.2%. RESULTS: Two hundred
      seventy-four eligible men completed the questionnaires; 132 (48%) reported having
      undergone prostatectomy and 142 (52%) reported having undergone radiotherapy.
      After age adjustment, the radiotherapy group reported more bowel dysfunction (P =
      0.001), whereas the prostatectomy group reported more urinary problems (P = 0.03)
      and more sexual dysfunction (P = 0.001). Scores for the FACT-G were similar in
      the two treatment groups. CONCLUSIONS: Men undergoing treatment for clinically
      localized prostate carcinoma continue to experience difficulty long after
      treatment. In this study, the prostatectomy group fared worse in regard to sexual
      and urinary functions, whereas the radiotherapy group experienced more bowel
      dysfunction. Survivor-reported QOL and treatment outcomes can assist physicians
      in counseling patients in the selection of the preferred course of treatment.

PMID- 9149027
TI  - Allium sativum (garlic) treatment for murine transitional cell carcinoma.
AB  - BACKGROUND: Currently, immunotherapy with Bacillus Calmette-Guerin (BCG) is the
      most effective treatment for superficial bladder carcinoma, but treatment-related
      toxicity may limit its use in some patients. Alternative treatments are needed
      for patients who fail to respond to BCG immunotherapy. Allium sativum (AS), or
      garlic, is known to have a broad range of biologic activities, including immune
      stimulation and reported antitumor activity. For these reasons, the authors
      conducted a series of experiments designed to explore the possible therapeutic
      effects of AS in the MBT2 murine bladder carcinoma model. METHODS: C3H/HeN mice
      were randomized prior to initiation of each experimental protocol. Mice received
      1 x 10(3) MBT2 cells in 0.1 mL RPMI-1640, administered subcutaneously into the
      right thigh, on Day 0 of the experiment. AS was injected at the site of tumor
      transplantation on Day 1 and at 2- to 7-day intervals up to Day 28. To evaluate
      the effects of oral AS in this model, treatment was initiated 30 days prior to
      tumor inoculation and continued for 30 days after tumor inoculation. Animals in
      all experiments were followed for tumor incidence, tumor growth, and survival.
      RESULTS: In the initial experiments, subcutaneous AS significantly reduced tumor
      volume compared with the saline control (P < 0.05). Unfortunately, treatment
      related death was also observed, requiring reduction in the total dose of AS.
      Animals that received 5 weekly immunizations of AS (5 mg, 5 mg, 1 mg, 1 mg, and 1
      mg; cumulative dose = 13 mg) had significantly reduced tumor incidence, tumor
      growth, and increased survival when compared with animals that received the
      saline control. No treatment-related deaths were observed with this treatment
      schedule. To determine whether systemic AS administration might be effective,
      orally administered AS was tested at doses of 5 mg, 50 mg, and 500 mg per 100 mL
      of drinking water. Mice that received 50 mg oral AS had significant reductions in
      tumor volume (P < 0.05) when compared with animals that received the saline
      control, and mice that received 500 mg oral AS had significant reductions in both
      tumor volume and mortality (P < 0.05). CONCLUSIONS: The significant antitumor
      efficacy of subcutaneous and oral AS warrants further investigation and suggests
      that AS may provide a new and effective form of therapy for transitional cell
      carcinoma of the bladder.

PMID- 9149028
TI  - Central neurocytoma: the role of radiation therapy and long term outcome.
AB  - BACKGROUND: It has been suggested that the biologic behavior of central
      neurocytoma is indolent, although little is known regarding the role of radiation
      therapy and long term outcome. To clarify the role of radiation therapy and long
      term outcome, the authors retrospectively analyzed 15 cases of central
      neurocytoma. METHODS: Clinical records and radiologic findings of 15 cases of
      central neurocytoma diagnosed at Seoul National University Hospital between
      January 1982 and February 1995 were carefully reviewed. The duration of follow-up
      was from 18-168 months (mean, 52 months); follow-up images were reviewed and the
      patient's Karnofsky performance scale (KPS) was assessed up to the time of last
      follow-up. RESULTS: The age of the patients ranged from 15 to 60 years (mean, 25
      years) and the male to female ratio was 11:4. Macroscopic total resection of the
      tumor was performed in seven patients, two of whom received fractionated
      radiation therapy. Subtotal removal of the tumor was performed in eight patients,
      five of whom received this same therapy. In 2 of the 5 patients who did not
      receive radiation therapy after macroscopic total resection, the tumors recurred
      8 and 21 months after surgery, respectively; in contrast, recurrence was not
      detected in the 2 patients who received fractionated radiation therapy after
      macroscopic total resection. In all five patients who received fractionated
      radiation therapy after subtotal resection, the tumor shrank (n = 3) or
      disappeared (n = 2) during the postsurgical follow-up period ranging from 27-113
      months; the tumor began to shrink from 6 months to 2 years after radiation. No
      change was found in the three patients who did not receive radiation therapy
      after subtotal resection. At the time of last follow-up, the KPS was greater than
      90 in all patients except one who required assistance in his daily activities
      because of complications from radiation therapy. CONCLUSIONS: It is suggested
      that even if the biologic behavior of a central neurocytoma is benign, radiation
      therapy appears to have an effect on tumor control. However, it should be
      carefully decided whether to use radiation therapy for a residual tumor because
      radiation can cause delayed complications and the clinical course of subtotally
      resected patients who do not receive radiation therapy is extremely benign.

PMID- 9149029
TI  - Secretory meningioma: clinical, histologic, and immunohistochemical findings in
      31 cases.
AB  - BACKGROUND: Secretory meningioma is a rare histologic variant characterized by a
      unique epithelial differentiation of meningothelial cells resulting in the
      production of hyaline inclusions. Most previous reports have presented single
      case observations. The authors selected 31 cases for a clinicopathologic study to
      characterize this type of tumor further. METHODS: Clinical data were compiled and
      the extent of peritumoral edema was assessed from preoperative computed
      tomography or magnetic resonance imaging scans. Preparations of surgical
      specimens of all tumors were studied after both conventional histologic and
      immunohistochemical preparations were made. Immunostaining was performed by
      either the avidin-biotin complex method or the alkaline phosphatase-antialkaline
      phosphatase method using 22 primary antibodies. RESULTS: In the tumor collection
      used in this study, secretory meningiomas represented 3% of meningiomas. The
      female-to-male ratio was 9:1. Most tumors were located at the sphenoid ridge or
      at the frontal convexity, and recurrences were not observed. Eighty-four percent
      of tumors presented with slight to marked peritumoral edema. The MIB-1 staining
      index showed a mean of 3.8%. Inclusions and surrounding cells consistently
      expressed epithelial membrane antigen, cytokeratins, carcinoembryonic antigen,
      and carbohydrate antigen 19-9. In decreasing frequency, they also contained
      alpha1-antitrypsin, immunoglobulin (Ig)A, alpha1-antichymotrypsin, IgM, and IgG.
      Cells positive for vimentin and S-100 did not contain inclusions. All tumors were
      positive for progesterone receptors. Macrophages were stained with antibodies to
      factor XIIIa, human leukocyte antigen-DR, and alpha1-antitrypsin. In 64% of
      cases, tumor vessels lacked expression of glucose transporter protein 1.
      CONCLUSIONS: The classification of secretory meningioma as a distinct variant has
      been justified on clinical, histologic, and immunohistochemical grounds. The
      unique epithelial features call attention to the broad spectrum of
      differentiation properties found in meningiomas.

PMID- 9149030
TI  - A phase I report of paclitaxel dose escalation combined with a fixed dose of
      carboplatin in the treatment of head and neck carcinoma.
AB  - BACKGROUND: Standard therapy for advanced head and neck carcinoma is surgery and
      radiation, and the subsequent 5-year survival with this treatment has been less
      than 50%. New combined modality treatment strategies are being tested to improve
      survival. New chemotherapy combinations are being developed and administered
      simultaneously with, or sequenced with, radiation and surgery. This article
      reports the Phase I results of administering paclitaxel and carboplatin
      preoperatively. The authors' objective was to develop an outpatient chemotherapy
      that would downstage tumors and allow organ preservation with equal or improved
      survival as compared with standard therapy. METHODS: Thirty-six patients with
      untreated Stage III/IV head and neck carcinoma were treated and were evaluable
      for toxicity. All patients had lesions that were measurable in perpendicular
      planes. A nonrandomized, Phase I design was used, according to which cohorts of
      patients were treated every 21 days with escalating doses of paclitaxel (150-265
      mg/m2) given as a 3-hour infusion immediately preceding carboplatin.
      Premedication was used to avoid acute hypersensitivity reactions. Carboplatin was
      administered intravenously over 1 hour at a constant dose calculated with the
      Calvert formula (area under the curve, 7.5). RESULTS: The dose-limiting
      toxicities were neuropathy and thrombocytopenia at a paclitaxel dose of 265
      mg/m2. Neutropenic fever was observed in 30% of patients at a paclitaxel dose of
      250-265 mg/m2. Other observed adverse effects included pruritus, myalgia,
      arthralgia, alopecia, nausea, and vomiting. CONCLUSIONS: Toxicity was acceptable.
      The maximum tolerated dose of paclitaxel was 230 mg/m2 without hematopoietic
      growth factor, or 250 mg/m2 with hematopoietic growth factor, the carboplatin
      dose held constant, calculated at area under the curve of 7.5. Phase II studies
      of this combination are warranted in the treatment of these carcinomas.

PMID- 9149031
TI  - Tamoxifen-associated venous thrombosis and activated protein C resistance due to
      factor V Leiden.
AB  - BACKGROUND: Thromboembolic events are well recognized complications of cancers
      and their treatment. Tamoxifen, an antiestrogen used in the treatment of breast
      carcinoma and other malignancies, has been associated with thrombotic events.
      Activated protein C resistance due to Factor V Leiden is the most prevalent
      inherited prothrombotic defect in populations of European descent and has been
      reported as a major cofactor in the development of thrombosis in women receiving
      estrogens. METHODS: The authors report three patients who developed
      thromboembolic complications while receiving tamoxifen. These patients were
      studied for the presence of activated protein C resistance by coagulation assay
      and the presence of Factor V Leiden by molecular analysis. RESULTS: All three
      patients had resistance to activated protein C by coagulation assay and were
      determined to be heterozygous for Factor V Leiden by molecular analysis.
      CONCLUSIONS: The authors propose that inheritance of Factor V Leiden
      significantly increases the risk of thrombosis in patients who receive tamoxifen
      therapy. All patients prescribed tamoxifen should be carefully questioned
      regarding personal and family histories of thrombosis and, when indicated,
      screened for Factor V Leiden.

PMID- 9149032
TI  - Neuroblastoma in adults and adolescents: an indolent course with poor survival.
AB  - BACKGROUND: Neuroblastoma rarely occurs in adults, and less than 10% of cases
      occur in patients older than 10 years. It has been suggested that the behavior of
      this disease may be different in older patients than in young children. The
      purpose of this study was to investigate the presentation, biologic features, and
      outcome of adolescent and adult patients with neuroblastoma to define differences
      from childhood neuroblastoma. METHODS: Medical record and pathology reviews were
      conducted for 16 patients age 13 years or older (13-33 years) at diagnosis who
      presented with neuroblastoma at the University of California-San Francisco (UCSF)
      during the period 1968-1995 (patients with intracerebral tumors,
      esthesioneuroblastoma, or ganglioneuroma were excluded). Six of these patients
      received their original diagnosis at UCSF, and the others were referred after
      diagnosis. The survival for the same period for all neuroblastoma patients ages
      13-18 years (n = 38) registered in the Children's Cancer Group (CCG) was compared
      with the survival for those ages 1-13 years (n = 1912). Three of the UCSF
      patients were enrolled in CCG studies. RESULTS: Biologic characteristics observed
      in adolescents and adults differed from those observed in younger patients. In
      the UCSF population, only 6 of 15 tested patients age 13 or older had elevated
      urinary catecholamines, and 0 of 6 tested patients had MYCN amplification. There
      were two patients with Stage I disease, three with Stage II, two with Stage III,
      and nine with Stage IV. Primary sites were adrenal, pelvic, and retroperitoneal
      in four cases each; mediastinal in two cases; and paraspinal in two cases.
      Metastases in nine patients at diagnosis were observed in bone in five; in bone
      marrow in four; in lymph nodes in three; in the liver in two; and in the pleura,
      breast, and dura in one patient each. 131I-metaiodobenzylguanidine uptake was
      observed in 9 of 11 patients. Initial treatment included surgery for 13 of 16
      patients, chemotherapy for 10 of 16, radiation therapy for 7 of 16, and
      autologous bone marrow transplantation for 1 of 16. Relapses occurred in 15 of 16
      patients and death in 13 of 16, with overall survival 30% 5 years after
      diagnosis. Only 1 patient currently remains free of clinical disease 24 months
      after diagnosis. Several of these patients had long courses from diagnosis to
      death, with multiple recurrences and/or chronic, persistent disease. In the CCG
      data base, 76% of patients ages 13-18 years had metastatic disease at diagnosis.
      In this group, only 1 of 32 had MYCN amplification. The actuarial survival of all
      CCG patients ages 13-18 years was 7% at 5 years and 4% at 10 years, whereas that
      for patients ages 1-13 years was 30% at 5 years and 23% at 10 years. CONCLUSIONS:
      Neuroblastoma in adolescents and adults has different biologic characteristics
      and a longer course than in children; nevertheless, ultimately the outcome is
      poor regardless of stage. A much more aggressive or innovative therapeutic
      approach is needed for these patients.

PMID- 9149033
TI  - A neuroblastoma cell line derived from a case detected through a mass screening
      system in Japan: a case report including the biologic and phenotypic
      characteristics of the cell line.
AB  - BACKGROUND: A mass screening system in Japan, which involves measuring urinary
      catecholamine metabolites, has resulted in an increasing number of cases of
      neuroblastoma, most of which have favorable biologic properties and some of which
      are associated with tumor regression or involution. At the time this study was
      begun, the characteristics and biologic nature of the neuroblastomas had not been
      fully defined, because a cell line had not yet been established with tumor tissue
      taken from a neuroblastoma detected in the mass screening. METHODS: The authors
      established a cell line by tissue culture for over 50 generations from a
      neuroblastoma found during mass screening, which was characterized by favorable
      histology, with a triploid DNA stemline and without N-myc gene amplification. The
      morphologic and biologic characteristics of the new cell line were investigated
      in vitro. RESULTS: The cell line, designated MASS-NB-SCH-1, has neuronal
      properties, such as neurite-like processes and neurofilaments, as well as the
      expression of vimentin and fibronectin in studies of the cell morphology and
      immunohistochemistry. Karyotype analysis detected the presence of 42-46
      chromosomes, with a deletion of the short arm of 1 of the 3 copies of chromosome
      1. DNA ploidy was near-diploid in association with 20-fold amplification of N-myc
      genes. CONCLUSIONS: The cell line has a nature distinct from the original tumor
      tissue. It may be characterized by phenotypic change caused by clonal selection
      or evolution of aggressive, proliferative properties in vitro. This cell line
      will be a useful model to investigate the properties of the neuroblastoma in
      relation to the N-myc amplification mechanism.

PMID- 9149034
TI  - The age peak in childhood acute lymphoblastic leukemia: exploring the potential
      relationship with socioeconomic status.
AB  - BACKGROUND: White children have a much higher incidence rate of acute
      lymphoblastic leukemia (ALL) than do African American children. This discrepancy,
      coupled with the geographic and temporal variations in the incidence of childhood
      ALL, have led to speculation that factors associated with socioeconomic status
      (SES) may play an important role in its etiology. Because most of the variation
      is accounted for by the occurrence of a peak in incidence between the ages of 2
      and 5 years, the purpose of this study was to compare the SES of children
      diagnosed with ALL between the peak ages of 2-5 years with those children
      diagnosed at other ages (birth-1 year and 6-14 years). METHODS: Patients included
      4210 children who were diagnosed with ALL between January 1, 1989 and December
      31, 1991 by a member institution of the Children's Cancer Group or the Pediatric
      Oncology Group. Of these children, 3614 were white and 596 were African American.
      The SES of a case was defined as the SES of the child's zip code of residence at
      the time of diagnosis. Five sociodemographic variable categories for each zip
      code were obtained from the 1990 U.S. Census including per capita income, number
      of housing units by household income, number of housing units by level of
      urbanization, number of persons older than 25 years by educational attainment,
      and number of persons by occupation. Mean values were compared for white children
      versus African American children, and peak ages (2-5 years) versus nonpeak ages
      (birth-1 year and 6-14 years) for both whites and African Americans. In addition,
      Wilcoxon's rank sum tests were performed. RESULTS: There were statistically
      significant differences between the means in each of the socioeconomic categories
      when African Americans were compared with whites. However, within race, the means
      of the SES variables for white children diagnosed during the peak ages (2-5
      years) were not significantly different from children diagnosed at other ages
      (birth-1 year and 6-14 years). Similarly, all but one of the comparisons for
      African American children yielded nonstatistically significant results. Similar
      results were obtained from the Wilcoxon's rank sum tests. CONCLUSIONS: The
      results of this analysis suggest that age differences in childhood ALL incidence
      may not be solely accounted for by SES differences.

PMID- 9149035
TI  - A comparison of breast, colorectal, lung, and prostate cancers reported to the
      National Cancer Data Base and the Surveillance, Epidemiology, and End Results
      Program.
AB  - BACKGROUND: The National Cancer Data Base (NCDB) is an information resource and
      program evaluation tool of the American College of Surgeons Commission on Cancer
      and the American Cancer Society that uses a hospital-based cancer reporting
      system. The Surveillance, Epidemiology, and End Results (SEER) program is a
      population-based registry program of the National Cancer Institute. The purpose
      of this investigation was to compare the aggregate NCDB data for selected cancer
      types from a given year with comparable SEER data. METHODS: SEER data from 1992
      on 18,322 breast, 13,427 colorectal, 15,276 lung, and 21,501 prostate cancers
      were compared with NCDB data on 96,323 breast, 69,456 colorectal, 108,702 lung,
      and 107,690 prostate cancers. RESULTS: Similar levels of data completeness were
      observed. The NCDB data tended to contain less complete information about the
      Spanish or Hispanic ethnicity of patients. Tumor grade data tended to be
      incomplete in both series. Stage information about lung and prostate cancer was
      more often missing in SEER data. Patient age, race, and gender in NCDB data
      differed little from corresponding SEER data, except that SEER data reported a
      greater proportion of patients in the "other" race category that included Asian
      Americans and American Indians. Tumor laterality, anatomic site, tumor grade, and
      types of surgical treatment were similar in the NCDB and SEER data. Radical
      mastectomy was performed in 49.4% of SEER breast cancer cases compared with 49.2%
      of NCDB cases. Cancer-directed surgery was observed less often among SEER
      prostate cancer cases than among NCDB cases. The NCDB data also indicated greater
      use of radiation therapy than the SEER data for the four types of cancer
      reviewed. CONCLUSIONS: The 1992 NCDB data, in aggregate, described patient and
      disease treatment characteristics and patterns that differed only marginally from
      those described in the SEER data from the same year.

PMID- 9149036
TI  - Small bowel manometry: short or long recording sessions?
AB  - The study of small bowel motility in humans is commonly done by one of two
      techniques: short-term recording in a stationary patient or long-term recording
      in an ambulatory patient. To compare the diagnostic yield of short- and long-term
      manometric studies of small intestinal motility, we reviewed all prolonged
      records performed in our center over the years. Long-term studies that included
      less than 6 hr of recording during fasting or less than 5 hr during sleep and
      short-term studies using the perfused tube technique were excluded, leaving
      91/121 tracings suitable for review. We analyzed the first 3 hr of the fasting
      period and the first 2 hr of the postprandial period on one occasion and the
      whole tracing on another; the fasting, postprandial and sleep period were
      analyzed separately. This allowed us to compare short and long recording sessions
      in the same patient. The two analyses agreed in 81/91 of the cases. In 7/10
      patients a study was diagnosed as abnormal in the short recording but was
      considered normal after review of the long recording, while the opposite occurred
      in the remaining three. Periods of sleep and fasting contributed similarly to the
      change in diagnosis. In another 6 patients with equivocal abnormalities during
      the short period, the long period helped to establish the diagnosis of normality
      with confidence. Most of the improvement in the long-term study came from
      extension of the studies during fasting to 6-7 hr from 3 hr. Long-term records of
      small bowel motility, including study during sleep enhance the diagnostic
      accuracy of the test. Accuracy can be improved also simply by prolonging the
      recording during fasting.

PMID- 9149037
TI  - Intestinal motility during hypoxia and reoxygenation in vitro.
AB  - Ischemia-reperfusion injury leads to profound functional and structural
      alterations of the gastrointestinal tract. We developed an in vitro model of
      reperfusion injury to study the changes in intestinal motility during hypoxia
      followed by reoxygenation. We recorded the spontaneous motor activity of
      intestinal rings from the proximal mouse jejunum, using force displacement
      transducers. In addition to the rhythmic contractions, we studied the contractile
      response to transmural stimulation of intrinsic nerves. During hypoxia, the
      frequency of the spontaneous contractions and the resting tension decreased.
      While 29% of the tissues still responded to neural stimulation after 15 min of
      hypoxia, electrical field stimulation did not evoke any response after 60 min of
      hypoxia. Reoxygenation resulted in a transient increase in the baseline tension
      and an initial normalization of the spontaneous rhythmic contractions, which
      subsequently became irregular. The percentage of tissues that recovered their
      ability to respond to electrical field stimulation 10 min after reoxygenation
      decreased from 100% after 15 min of hypoxia to 47% after 60 min of hypoxia. The
      administration of the antioxidant glutathione prevented the functional
      abnormalities seen 10 min after reoxygenation. The pharmacological inhibition of
      Cu,Zn superoxide dismutase exacerbated the functional reoxygenation damage.
      Conversely, the overexpression of this radical-scavenging enzyme in transgenic
      mice increased the likelihood of functional recovery. Reoxygenation in a calcium
      free solution also prevented prolonged functional damage of the muscle rings. We
      conclude that hypoxia-reoxygenation significantly alters intestinal motility. The
      generation of reactive oxygen species and disruptions in the calcium homeostasis
      play an important role in the pathogenesis of reoxygenation damage. Interventions
      that alter the intracellular redox state or affect the secondary changes in the
      intracellular calcium concentration can prevent or blunt the effects of
      reoxygenation injury on intestinal motility.

PMID- 9149038
TI  - Electrical stimulation at a frequency higher than basal rate in human stomach.

PMID- 9149039
TI  - Efficacy of electrical stimulation at frequencies higher than basal rate in
      canine stomach.
AB  - The optimum frequency for electrically stimulating motility in the stomach is
      still in question. Some studies of gastric electrical stimulation (GES) at near
      physiologic frequencies have reported gastric electrical entrainment but with
      little efficacy in improving motility. In this study we examined the
      effectiveness of electrical stimulation at a broad range of frequencies in
      entraining gastric electrical activity (GEA) and eliciting contractions in a
      canine model. The stomachs of six dogs, each implanted with four pairs of
      stainless steel electrodes and two strain gauges were stimulated at frequencies
      ranging from 3 to 30 cycles/min. GEA and contractions were monitored before and
      during electrical stimulation. The ability of GES at different frequencies to
      reverse the effect of glucagon was also investigated. GEA was entrained in most
      animals at frequencies close to the intrinsic rate as well as at four to five
      times the intrinsic rate. At other stimulation frequencies, the recorded
      electrical control activity either remained unchanged, uncoupled, or became
      dysrhythmic. Contractile response to stimulation at four to five times the
      intrinsic rate were significantly higher than those at frequencies close to the
      intrinsic rate (P < 0.05). GES did not alter the effect of glucagon. Stimulation
      at a frequency of four times the basal rate of 5/min elicited the largest
      motility index in dogs. Stimulation at frequencies much higher than the
      physiologic rate warrants further study as a possible optimum range for GES.

PMID- 9149041
TI  - Expression of muscarinic receptor subtypes in rat gastric smooth muscle: effect
      of M3 selective antagonist on gastric motility and emptying.
AB  - Expression of muscarinic receptor subtypes in rat gastric smooth muscle was
      examined with reverse transcriptase-polymerase chain reaction (RT-PCR). Under the
      condition for detecting the messages of m1-m4 subtypes in brain, atrium, and
      gastric mucosa, only the fragments of m2 and m3 subtypes were amplified with RNA
      prepared from rat gastric smooth muscles. Furthermore, the amplified fragments
      were digested by restriction enzymes, reconfirming that the predicted size
      products of m2 and m3 contain the partial DNA sequences of m2 and m3 subtypes,
      respectively. We measured gastric motility in rats with a pressure transducer
      system under the continuous venous infusion of the muscarinic antagonists
      atropine and butylscopolamine (nonselective), AF-DX 116 (M2), zamifenacine (M3),
      and glucagon. Heart rate was monitored simultaneously in the tail. Gastric
      motility was inhibited in the presence of glucagon and zamifenacine without
      alteration of heart rate, whereas there was no inhibition in the presence of AF
      DX 116 even after the augmentation of heart rate was observed. Gastric emptying
      was also suppressed in the presence of zamifenacine, which had an effect
      comparable with that of atropine, butylscopolamine, and glucagon. These results
      indicate that the activation of the M3 subtype in gastric smooth muscle causes
      its contraction, and the M3 selective antagonist could be a potentially useful
      drug without an adverse effect on the heart for radiological and endoscopic
      examination in the upper gastrointestinal tract.

PMID- 9149040
TI  - Impaired gastric myoelectrical activity in patients with chronic renal failure.
AB  - Dysmotility and delayed emptying of the stomach have been reported in patients
      with chronic renal failure (CRF). The aim of this study was to investigate
      whether gastric myoelectrical activity was impaired in patients with CRF using
      electrogastrography. The electrogastrogram (EGG) was recorded in 24 symptomatic
      patients with CRF (15 with diabetes) and 12 normal subjects. Two 30-min EGG
      recordings before and after a test meal were analyzed using spectral analysis
      methods. It was found that patients with CRF showed a significantly lower
      percentage of normal 2-4 cpm slow waves in both fasting and fed states in
      comparison with healthy controls (in fasting state: 88.9 +/- 2.5% vs 67.4 +/-
      6.6%/63.2 +/- 7.0%, P < 0.01; in fed state: 89.6 +/- 1.8% vs 64.6 +/- 6.2%/62.0
      +/- 8.3%, P < 0.01; controls vs diabetic patients/nondiabetic patients). Both
      patient groups showed a significantly higher prevalence of the abnormal EGG,
      which was defined as the percentage of 2-4 cpm slow waves lower than 70% (fasting
      state: 8% vs 60%/56%, P < 0.01/0.05; fed state: 0% vs 53%/56%, P < 0.005/0.002;
      controls vs diabetic patients/nondiabetic patients). No significant difference
      was observed in the regularity of the gastric slow waves between the two patient
      groups. The healthy controls showed a significant increase in the dominant power
      and frequency of the EGG after the test meal. However, this increase was absent
      in the two patient groups. It was concluded that patients with chronic renal
      failure have abnormal gastric myoelectrical activity, including impaired
      regularity of the gastric slow wave and a failed increase in the power of the EGG
      at 3 cpm. Electrogastrography is an attractive noninvasive method for the study
      of gastric motility in patients with severe chronic renal failure.

PMID- 9149042
TI  - Gastric emptying in OLETF rats not expressing CCK-A receptor gene.
AB  - We have very recently demonstrated the low acidity of gastric juice and the high
      susceptibility to the development of gastric ulceration in Otsuka Long-Evans
      Tokushima Fatty (OLETF) rats not expressing CCK-A receptors. In the present
      study, gastric emptying in this strain was examined and compared with control
      Long-Evans Tokushima Otsuka (LETO) rats. Gastric emptying was evaluated by the
      phenol red method. Gastric emptying 30 and 60 min after a liquid meal in OLETF
      rats was significantly delayed compared to that in control LETO rats.
      Intraperitoneal injection of CCK-8 at a dose of 5 microg/kg significantly
      inhibited gastric emptying in control LETO rats, whereas the same dose of CCK-8
      failed to inhibit gastric emptying in OLETF rats. These results suggest for the
      first time that gastric emptying was suppressed in OLETF rats. We also confirmed
      with this mutant that CCK delays gastric emptying through the CCK-A receptors.

PMID- 9149043
TI  - Aspirin, but not sodium salicylate, indomethacin, or nabumetone, reversibly
      suppresses 1,2-dimethylhydrazine-induced colonic aberrant crypt foci in rats.
AB  - The aim of this study was to determine if selective inhibition of cyclooxygenase
      isozymes affects the initiation of carcinogen-induced colon cancer using aberrant
      crypt foci (ACF) as a surrogate biomarker. Male Sprague-Dawley rats (18 per
      group) were given single subcutaneous injections of saline (4 ml/kg), aspirin (50
      mg/kg body wt) sodium salicylate (50 mg/kg), indomethacin (4 mg/kg), nabumetone
      (100 mg/kg), or 16,16-dimethyl-prostaglandin E2 (50 mg/kg) for three days. On day
      4, 12 rats per group were given a subcutaneous injection of 1,2-dimethylhydrazine
      (12 mg base/kg body wt) and six rats per group received vehicle alone (4 ml/kg)
      every week for eight weeks, after which drug treatment ceased. Control and six
      carcinogen-treated rats per group were killed at this time and the remaining six
      rats per group killed 22 weeks later. Colons were scored for ACF number and size.
      Only aspirin caused a significant reduction in total ACF and ACF formation at the
      early time point, but at the later time, there were no significant differences
      between groups. ACF from all treatment groups increased in size at similar rates
      at both time points. Thus, only aspirin demonstrated a significant, although
      reversible, suppression of carcinogen-induced ACF. Possible mechanisms of action
      and the clinical implications of aspirin chemoprevention are discussed.

PMID- 9149044
TI  - Amplification of BCR protein associated with oncogenesis in human hepatocellular
      carcinoma.
AB  - The BCR gene is located on human chromosome 22. The normal cellular BCR gene
      encodes a 160,000-dalton phosphoprotein associated with a serine/threonine kinase
      activity. The BCR protein is involved in signal transduction. We investigated the
      expression of the BCR protein in hepatocellular carcinoma (HCC), surrounding
      noncancerous liver tissue, liver cirrhosis (LC), chronic hepatitis (CH), and
      normal liver with immunohistochemistry and a western blot analysis. BCR
      immunoreactivity was detected using a monoclonal antibody. In normal liver, and
      both CH and LC without association of HCC, the immunoreactivity of the BCR
      protein was minimal. In contrast, 73% (22 of 30) of noncancerous liver tissue
      adjacent to the HCC and 40% (12 of 30) of HCC expressed BCR protein; this
      difference was statistically significant (P < 0.01). The expression of the BCR
      protein expression correlated with the degree of histological differentiation of
      HCC (P < 0.05). In addition, the amplification of BCR protein in noncancerous
      cells was supported by the detection of specific protein using a western blot
      analysis. In two cases, the expression of BCR protein occurred only in overtly
      malignant HCC cells. As a result, the expression of the BCR protein may be
      associated with oncogenesis in human HCC.

PMID- 9149047
TI  - Characteristics of patients with single versus multiple cholesterol gallstones.

PMID- 9149046
TI  - Does antecedent ethanol intake affect course of taurocholate pancreatitis in
      rats?
AB  - The pathogenic role of acute ethanol abuse in acute pancreatitis (AP) is still
      obscure. The aim of the study was to evaluate the effect of antecedent intake of
      a high dose of 40% ethanol (5 g/kg body wt.), on trypsinogen activation,
      pancreatic lysosomal membrane labilization, and activities of phospholipase A2
      and lipase in taurocholate AP in rats. In 80 male Wistar rats, AP or sham
      operation (SO) was produced 6 hr after intragastric saline (S) or ethanol (E)
      administration, and animals were sacrificed after 6, 12, and 18 hr. Free active
      trypsin (FAT) and total potential trypsin (TPT) were assayed in the pancreatic
      homogenate. Percentage free activity (%F/T) of cathepsin B was determined as an
      index of lysosomal membrane fragility. The most evident activation of trypsin
      occured at 6 hr AP (11.6% of TPT in S group and 16.4% in E group). Antecedent
      ethanol increased FAT 18 hr after SO from 0.105 +/- 0.048 microg/g protein to
      0.258 +/- 0.054 and AP lasting 18 hr from 0.331 +/- 0.072 to 0.695 +/- 0.110. The
      %F/T of cathepsin B was highest at 18 hr of AP, suggesting maximal labilization
      of lysosomal membranes at this time. This labilization occurred earlier (at 12 hr
      of AP) in E group. The increasing effect of antecedent E on lipolytic enzymes was
      evident after 6 hr of AP. In conclusion, the antecedent intake of high dose of
      ethanol significantly promoted the conversion of trypsinogen to trypsin in
      taurocholate acute pancreatitis, whereas its additional effect toward
      labilization of pancreatic lysosomal membranes and the increase of lipolytic
      enzymes activities was less evident. Therefore, the promoting impact of acute
      ethanol intake in the development of acute pancreatitis could be mainly dependent
      on its increasing effect on trypsinogen activation.

PMID- 9149048
TI  - Noninvasive monitoring of hemodynamic changes in acute pancreatitis in rabbits.
AB  - Hemodynamic parameters of experimental acute necrotizing pancreatitis (AP) were
      monitored by means of echocardiography in rabbits. Left ventricular (LV) systolic
      and diastolic parameters were determined before and 1, 3, 6, 12, 18, and 24 hr
      after injection of taurocholic acid in the pancreatic duct in AP animals.
      Temporary LV dilatation was observed 6 hr after the AP induction [LV end
      diastolic (ED) diameter from 1.16 +/- 0.04 to 1.22 +/- 0.04 cm, P < 0.05, ED
      volume from 2.98 +/- 0.34 to 3.57 +/- 0.75 ml, P < 0.05] without decrease in
      systolic function. Cardiac output (CO) and stroke volume (StV) was increased in
      both groups 3 hr after the operation (from 0.53 +/- 0.15 to 0.71 +/- 0.06 L/min,
      P < 0.05 in AP), but in the AP animals it remained high. However, 24 hr after AP
      induction, both the CO and the StV were decreased significantly. The LV diastolic
      function was impaired 1 hr after AP induction, but had recovered after 12 hr. In
      conclusion, an early diastolic impairment followed by LV enlargement could be
      noninvasively observed in experimental AP in rabbits.

PMID- 9149045
TI  - Liver-spleen infarcts following transcatheter chemoembolization: a case report
      and review of the literature on adverse effects.

PMID- 9149050
TI  - Phospholipase A2 secretion during intestinal graft ischemia.
AB  - The time-dependent appearance of phospholipase A2 (PLA2) activity in the
      preservation media of ischemic rat intestinal grafts is described. In controls,
      Ca2+-dependent, secretory PLA2 activity accumulated rapidly during the first 6 hr
      of ischemia, followed by a linear increase for up to 48 hr. LDH levels, by
      contrast, increased linearly throughout the 48 hr of ischemia. Addition of
      inhibitors of PLA2, cyclooxygenase, and lipooxygenase blocked accumulation of
      PLA2, but not LDH. PX-13, a novel PLA2 inhibitor, was most effective: 40 microM
      inhibited release by 86%, while 25 microM indomethacin (cyclooxygenase blocker)
      or nordihydroguiaretic acid (lipooxygenase blocker) inhibited 41 and 36%,
      respectively. That appearance of PLA2 activity, but not LDH, is attenuated by
      inhibitors of the eicosanoid cascade suggests a secretory event rather than
      leakage from dying cells. The secreted PLA2 is most likely the proinflammatory
      sPLA2 that has been implicated as a stress-induced protein and priming agent in
      ischemia-reperfusion injury.

PMID- 9149051
TI  - Aminocaproic acid used to control upper gastrointestinal bleeding in radiation
      gastritis.

PMID- 9149049
TI  - Differential effect of nitric oxide inhibition as a function of preservation
      period in pancreas transplantation.
AB  - The role of nitric oxide, produced during reperfusion as a function of
      preservation time, in the development of the inflammatory process in pancreas
      transplantation has been explored. For this purpose, the effect of nitric oxide
      synthase inhibition, as well as 6-keto-prostaglandin F1alpha, leukotriene B4, and
      lipoperoxidation levels were evaluated in an experimental model of rat pancreas
      transplantation after different periods of cold preservation. The results show
      posttransplantation increases in 6-keto-prostaglandin F1alpha, leukotriene B4,
      and lipoperoxidation levels in pancreatic tissue and in plasma lipase. When
      ischemia was induced for 30 min, nitric oxide synthase inhibition prevented these
      increases, and L-arginine was able to reverse this effect. By contrast, nitric
      oxide synthase inhibition has no effect when ischemia was prolonged for 12 hr. In
      summary, this study suggests that, during reperfusion, nitric oxide modulates 6
      keto-prostaglandin F1alpha synthesis, lipoperoxidation levels, and the
      development of pancreatic injury but only when the ischemic period is quite
      short.

PMID- 9149052
TI  - Association of nonsteroidal antiinflammatory drugs with outcome in upper and
      lower gastrointestinal bleeding.
AB  - Although nonsteroidal antiinflammatory drug (NSAID) use is strongly associated
      with both upper gastrointestinal bleeding (UGIB) and lower gastrointestinal
      bleeding (LGIB), few data exist regarding the outcome of the bleeding episode for
      those consuming these drugs. Consecutive patients with UGIB or LGIB evaluated
      during the period August 1, 1990 through September 30, 1994 at a large inner city
      hospital were prospectively identified. Both prescription and over-the-counter
      NSAID use was specifically evaluated. Endoscopy was performed in most patients
      for diagnosis. Outcome measures included transfusion requirement, hospital stay,
      need for endoscopic therapy or surgery, and death. Over the 50-month study
      period, 785 patients admitted with UGIB and 161 with LGIB were studied. NSAID use
      was documented in 59% of patients with UGIB and 51% with LGIB. In UGIB, NSAID
      users were more likely to be female and older. NSAID users had a significantly
      shorter median hospital stay (4 vs 5 days), less rebleeding (11% vs 18%; P =
      0.004) and in-hospital mortality (5% vs 13%; P = 0.001) as compared to nonusers.
      These differences remained significant when controlling for age, race, and
      gender. Similar trends in outcome were seen when evaluating ulcer- and non-ulcer
      related bleeding. NSAID users with LGIB were more likely to be female, although
      rebleeding (19% vs 21%), hospital stay, and in-hospital mortality (5% vs 2%) were
      not significantly different between users and nonusers. UGIB in NSAID users
      appears to have a better prognosis as compared to nonusers. In contrast, NSAID
      use does not appear to be associated with outcome in patients with LGIB.

PMID- 9149054
TI  - Effect of pneumatic dilation on gastroesophageal reflux in achalasia.
AB  - The aims of this study were to assess the effect of pneumatic dilation on
      gastroesophageal reflux in achalasia, differentiate esophageal acid due to
      lactate from acid due to gastroesophageal reflux, and determine if chest pain and
      heartburn are reliable indicators of gastroesophageal reflux. Eight untreated
      achalasia patients underwent pre- and postdilation esophageal fluid/food residue
      lactate and pH analysis, esophageal manometry, 24-hr pH monitoring, and symptom
      assessment. All patients had a successful clinical outcome and a decrease in
      lower esophageal sphincter pressure from 29.1 +/- 12.7 to 14.7 +/- 3.8 mm Hg
      (mean +/- SD; P = 0.04). Abnormal acid exposure was present in two patients
      before and two patients after dilation. Postdilation acid exposure was mild.
      Lactate was detected before dilation in all patients. A lactate concentration >2
      mmol/liter was associated with acidic residue and one abnormal 24-hr pH profile.
      There was no correlation between an abnormal 24-hr pH test and age, lower
      esophageal sphincter pressure, or duration of symptoms prior to treatment. Chest
      pain and heartburn were unrelated to drops in pH. Gastroesophageal reflux is rare
      in untreated achalasia and esophageal acidity may result from ingestion of acidic
      foods or production of lactate. Mild gastroesophageal reflux occurs after
      dilation but is of no clinical significance. Chest pain and heartburn are not
      indicators of acid reflux in achalasia.

PMID- 9149053
TI  - Nonsteroidal antiinflammatory drugs are associated with both upper and lower
      gastrointestinal bleeding.
AB  - To evaluate the association between nonsteroidal antiinflammatory drug (NSAID)
      use and upper gastrointestinal bleeding (UGIB) and lower gastrointestinal
      bleeding (LGIB), we performed a prospective case-control study at a large inner
      city hospital over a 28-month period evaluating 461 consecutive patients
      hospitalized for UGIB and 105 with LGIB. During the same period, 1895 in-patients
      evaluated by our gastroenterology consultative service served as controls. At the
      time of initial evaluation, all patients were asked about the use of any
      prescription or over-the-counter NSAID product within one week of admission.
      Endoscopic examination was performed in most patients with bleeding. NSAID use
      was almost equivalent in patients with UGIB and LGIB (60%) and significantly
      greater than controls [34%; P < 0.001; odds ratio (OR) 3.0; 95% CI, 2.4-3.6]. The
      age, race, and gender adjusted risk for LGIB associated with NSAID use was
      significant [adjusted OR (AOR) 2.6; 95% CI 1.7-3.9], although less than UGIB (AOR
      3.2; P = 0.34). The risk associated with diverticular bleeding (N = 53, AOR 3.4;
      95% CI 1.9-6.2) was higher than duodenal ulcer bleeding although not
      significantly (N = 97, AOR 3.0). We conclude that NSAID use is strongly
      associated with LGIB and from lesions not considered associated with mucosal
      ulceration such as diverticulosis.

PMID- 9149055
TI  - Adaptation of esophageal mucosa to acid- and pepsin-induced damage: role of
      nitric oxide and epidermal growth factor.
AB  - To study whether the esophageal mucosa was able to elicit mucosal adaptation, we
      induced esophageal damage by perfusing acidified pepsin in rabbits. Mucosal
      adaptation was induced by preexposing the esophageal mucosa to a mild irritant
      (acidified saline) for 60 min prior to acidified pepsin (strong irritant).
      Macroscopic and microscopic esophageal injury, cell proliferation, and mucosal
      barrier function (H+, K+, hemoglobin flux rates) were studied. Preexposure of the
      esophageal mucosa to acidified saline significantly decreased both the mucosal
      damage and the mucosal barrier dysfunction induced by acidified pepsin. The
      development of this phenomenon was nondependent on cell proliferation.
      Concomitant treatment with either the nitric oxide synthase inhibitor, N(G)-nitro
      L-arginine, or the perfusion of immunospecific EGF-receptor antibodies or
      tyrphostin-25, an inhibitor of the tyrosine kinase activities ligated to the
      intracytoplasmatic domain of the EGF receptor, during the preexposure period
      completely reversed the protection induced by acid. We conclude that the rabbit
      esophageal mucosa shows mucosal adaptation to acid and pepsin. The development of
      this phenomenon is fast, not dependent on cell proliferation, and dependent, at
      least in part, on nitric oxide and EGF-receptor-mediated mechanisms.

PMID- 9149056
TI  - Salivary carbonic anhydrase protects gastroesophageal mucosa from acid injury.
AB  - Saliva contains several factors that protect the alimentary canal mucosa against
      acidity. We measured the secretory carbonic anhydrase (CA VI) levels in the
      saliva of patients with gastrointestinal disorders using a time-resolved
      immunofluorometric assay. The mean enzyme concentrations were found to be lower
      in patients with verified esophagitis, gastric ulcer, or duodenal ulcer than in
      control patients with nonacid peptic diseases. The biochemical data from the
      enzyme activity assays and western blots of the human gastric mucosa and gastric
      juice samples indicated that the swallowed CA VI probably retains its activity in
      the harsh environment of the gastric lumen. In the upper alimentary canal, CA VI
      may neutralize the acid by catalyzing the formation of carbon dioxide and water.
      The present findings suggest that drugs supplemented with CA VI may prove
      beneficial in treating acid-peptic diseases.

PMID- 9149059
TI  - Placement of a coated esophageal metallic mesh stent inside an uncoated stent as
      treatment of tracheoesophageal fistula.

PMID- 9149057
TI  - Histological effect of (R)-alpha-methylhistamine on ethanol damage in rat gastric
      mucosa: influence on mucus production.
AB  - (R)-alpha-Methylhistamine, a selective agonist of histamine H3 receptors,
      prevents macroscopically visible gastric lesions by absolute ethanol in the rat.
      A further insight into its activity was the aim of our study. Rats were given
      saline or (R)-alpha-methylhistamine (100 mg/kg) intragastrically. After 30 min,
      absolute ethanol was given and gastric mucosa was sampled 60 min later.
      Histologic damage and intracellular and adherent mucus were quantified. Luminal
      surface and mucous cells were examined by scanning and transmission electron
      microscopy. (R)-alpha-Methylhistamine reduced the extent of lesions by ethanol
      from 96 to 18%. Surface mucous cells and mucous neck cells were increased in
      volume and number, packaging of intracellular mucus was modified, and the
      secretory processes were promoted by (R)-alpha-methylhistamine itself, although
      these modifications were mostly evident in stomachs subsequently exposed to
      ethanol. Adherent mucus layer thickness was increased by (R)-alpha
      methylhistamine only after ethanol exposure. It is concluded that (R)-alpha
      methylhistamine predisposes mucous cells to react to ethanol.

PMID- 9149058
TI  - Pentadecapeptide BPC 157, cimetidine, ranitidine, bromocriptine, and atropine
      effect in cysteamine lesions in totally gastrectromized rats: a model for
      cytoprotective studies.
AB  - A superior effectiveness in various lesion assays was noted for the novel
      pentadecapeptide BPC 157, originated from human gastric juice protein (BPC) and
      claimed to be a cytoprotective agent. From this viewpoint, as a previously
      untreated experimental improvement to create an acid-free environmental for
      cytoprotection studies, total gastrectomy was done 24 hr before the ulcerogenic
      procedure. In the absence of stomach and gastric acid, the damaging effects of
      cysteamine (400 mg/kg subcutaneously, death 24 hr thereafter), to date thought to
      be an acid-related duodenal ulcerogen, and the BPC 157 cytoprotective effect (10
      microg or 10 ng/kg intraperitoneally) were further challenged. BPC 157 was
      compared with reference agents [cimetidine (50), ranitidine (10), omeprazole
      (10), bromocriptine (10) and atropine (10) (mg/kg intraperitoneally, 1 hr before
      cysteamine] known to be also cytoprotective. In naive rats, with intact stomach,
      all of them showed a strong beneficial effect. Interestingly, in gastrectomized
      animals, the application of BPC 157 or the reference agents before cysteamine
      significantly prevented the otherwise severe duodenal lesion development noted in
      the control gastrectomized cysteamine rats. In groups without cysteamine, no
      lesions were noted (laparotomy, gastrectomy only, 24 or 48 hr postsurgical
      period), nor was lesion potentiation seen in cysteamine-treated laparotomized
      animals. In summary, these findings--equal damaging effect of cysteamine and
      equal protection of pentadecapeptide BPC 157 and reference agents in
      gastrectomized and rats with intact stomach--seem to be particularly relevant for
      a cytoprotective viewpoint. Without a stomach, the cysteamine damaging effect was
      convincingly defined as an essential gastric acid-independent injury (analogous
      to ethanol gastric lesions). Likewise, a high "cytoprotective capacity,"
      apparently acid independent, common for all tested agents (novel pentadecapeptide
      BPC 157, cimetidine, ranitidine, omeprazole and atropine) could be clearly
      stressed.

PMID- 9149060
TI  - Composite tumor of the esophagus with tripartite differentiation.

PMID- 9149061
TI  - Increased nitric oxide production and inducible nitric oxide synthase activity in
      colonic mucosa of patients with active ulcerative colitis and Crohn's disease.
AB  - It is postulated that an enhanced production of nitric oxide by inflamed
      intestine plays a role in the pathophysiology of active inflammatory bowel
      disease. In this study, systemic NOx concentrations and colonic nitric oxide
      synthase activity were determined in patients with ulcerative colitis or Crohn's
      disease. The relationship between these two parameters and disease activity, as
      well as differences in nitric oxide synthase activity between ulcerative colitis
      and Crohn's disease, were areas of specific focus. Patients with active
      ulcerative colitis and Crohn's disease had significantly elevated plasma NOx
      concentrations; a positive correlation was found between NOx values and inducible
      nitric oxide synthase activities in the active mucosa of these patients. In
      active ulcerative colitis, levels of inducible nitric oxide synthase were
      significantly elevated in both normal and inflamed mucosa, although inducible
      nitric oxide synthase activity was higher in the latter. These colonic inducible
      nitric oxide synthase activities correlated well with the results of endoscopic
      and histologic grading of inflammation. There was no increase in constitutive
      nitric oxide synthase activity in patients with active ulcerative colitis.
      However, constitutive nitric oxide synthase activity was significantly increased
      in the inflamed mucosa in patients with Crohn's disease. In Crohn's disease,
      elevated inducible nitric oxide synthase activity was found in both normal and
      inflamed mucosa, with no significant difference between the tissues. Such
      differences in nitric oxide production in the colonic mucosa possibly reflect the
      significant differences in the pathophysiology and characteristic clinical
      features between ulcerative colitis and Crohn's disease.

PMID- 9149062
TI  - Intestinal effects of sulfate in drinking water on normal human subjects.
AB  - Uncontrolled observations implicate sulfate in drinking water at concentrations
      exceeding 500-700 mg/liter as a cause of diarrhea, but controlled studies have
      not been reported. We conducted a controlled study in normal adults to determine
      the effect of various drinking water sodium sulfate concentrations on bowel
      function. Ten healthy subjects were given a constant diet and fluid intake. Fluid
      consisted of 36 ml/kg/day of drinking water of various known sulfate
      concentrations and 500 ml of other fluid. In a dose-ranging study, four subjects
      received drinking water with sulfate concentrations of 0, 400, 600, 800, 1000,
      and 1200 mg/liters for six consecutive two-day periods. In a single-dose study,
      six other subjects received water with sulfate concentrations of 0 and 1200
      mg/liter for two consecutive six-day periods. Stool mass, frequency, and
      consistency and mouth-to-anus appearance time of colored markers were measured.
      In the dose-ranging study, the only significant linear trend was decreasing mouth
      to-anus appearance time with increasing sulfate concentrations. In the single
      dose study, 1200 mg/liter sulfate caused a significant but clinically mild
      increase in mean stool mass per six-day pool from 621 g to 922 g (P = 0.03). When
      all 10 subjects were used to compare effects of 0 mg/liter and 1200 mg/liter
      sulfate, significant differences in stool consistency (P = 0.02) and transit time
      (P = 0.03) were observed. None of the subjects reported diarrhea or passed more
      than three stools per day. In 10 normal adult subjects, sulfate in drinking water
      at a concentration of 1200 mg/liter, which is higher than reported to occur in US
      municipal water sources, caused a measurable but clinically insignificant
      increase in stool mass and decrease in stool consistency and appearance time, but
      no change in stool frequency and no complaint of diarrhea.

PMID- 9149063
TI  - Ontogenetic development and distribution of antibody transport and Fc receptor
      mRNA expression in rat intestine.
AB  - The intestine of the suckling rat has the unique capacity of absorbing
      immunoglobulins from maternal milk. We investigated intestinal Fc receptor mRNA
      expression and the absorption of orally administered antibodies to delineate the
      ontogeny and tissue specificity of this transport system. Duodenal expression of
      Fc receptor mRNA was at maximum levels between 1 and 19 days of age, but was not
      detectable during fetal life and in animals after weaning. Along the horizontal
      axis of the intestine, FcRn mRNA expression was maximum in the proximal duodenum
      and declined gradually in distal bowel. Similarly, absorption of orally
      administered antibody was low shortly after birth, but reached maximum levels at
      14 days of age. By the time of weaning, antibody uptake had almost completely
      ceased. These data further delineate the temporal and spatial nature of the
      intestinal immunoglobulin transport system, and represent additional examples of
      how the intestinal Fc receptor is transcriptionally regulated.

PMID- 9149064
TI  - Gastric lipase secretion after sham feeding and cholinergic blockade.
AB  - Our purpose was to examine gastric lipase secretion after cephalic stimulation
      (sham feeding) and to examine the effect of cholinergic blockade. Eight healthy
      volunteers, four women and four men, age 21-58 years, were studied twice on
      separate days. They were sham fed with and without infusion of atropine. Gastric
      content was measured and the amount as well as the activity of gastric lipase
      output were determined. Plasma concentrations of gastrin, secretin, and
      cholecystokinin (CCK) were measured simultaneously by radioimmunoassays. Cephalic
      stimuli can evoke human gastric lipase secretion, and this effect was almost
      ablated by atropine blockade of cholinergic receptors. The concentrations of CCK
      and secretin in plasma were unaffected by sham feeding with or without atropine
      blockade, whereas gastrin was stimulated by sham feeding after atropine blockade.
      Gastric lipase secretion in man is apparently controlled by interacting vagal and
      hormonal mechanisms.

PMID- 9149065
TI  - Hypersensitivity to 5-ASA suppositories.

PMID- 9149066
TI  - Diffuse mesenteric amyloidosis.

PMID- 9149067
TI  - Gastrospirillum hominis gastritis in a child with celiac sprue.

PMID- 9149068
TI  - cDNA sequencing of the 5' noncoding region (5' NCR) to determine hepatitis C
      genotypes in patients with chronic hepatitis C.
AB  - Reports suggest that response to interferon-alpha therapy is influenced by both
      hepatitis C viral genotype and titer. Our aim was to determine if direct,
      automated, cycle sequencing of the PCR product from an HCV RNA detection assay
      could be used to reliably determine HCV genotype. In addition, the approach was
      used to determine the HCV genotype distribution in our patient population and to
      learn if there was a correlation between HCV genotype and RNA titer that could be
      used to predict response to treatment. In all 143 consecutive patients were
      tested for both HCV RNA titer and genotype. Automated, cycle sequencing of PCR
      product was highly effective and failed to yield a genotype in only 3 (2%)
      patients. The distribution of HCV genotypes was: 1a (40%), 1b (39%), 2a (2%), 2b
      (6%), 3a (4%). There were significant differences in the median HCV RNA titers
      between genotypes 1, 2, and 3. High HCV RNA titers >4.4 x 10(6) copies/ml were
      only seen in genotype 1. However, the HCV RNA level should not be used as a
      surrogate marker of genotype because of a significant overlap of titers within
      the genotypes.

PMID- 9149070
TI  - Study of immune reactivity of minocycline-induced chronic active hepatitis.

PMID- 9149071
TI  - Treatment of inflammatory myopathies.
AB  - The treatment of the immune-mediated inflammatory myopathies remains largely
      empirical. Corticosteroids are usually effective in polymyositis and
      dermatomyositis but may need to be combined with methotrexate or azathioprine in
      some patients. Intravenous immunoglobulin (IVIg) is effective as add-on therapy
      in some patients not adequately controlled with steroids or immunosuppressive
      agents, but further controlled trials of IVIg are necessary to define the
      indications and optimal dose regimens. Cyclophosphamide, cyclosporin, or
      chlorambucil may be effective in patients with refractory polymyositis or
      dermatomyositis. Low-dose whole body or lymphoid irradiation is a last option in
      severely disabled patients resistant to all other treatments. As a small
      proportion of patients with inclusion body myositis respond to corticosteroid or
      immunosuppressive therapy, a 3-6-month trial of such therapy is justified in this
      condition. More specific immunotherapy for these disorders awaits identification
      of the target antigens and further clarification of the immunopathogenetic
      mechanisms.

PMID- 9149072
TI  - Direct muscle stimulation in acute quadriplegic myopathy.
AB  - We have previously found that muscle is electrically inexcitable in severe acute
      quadriplegic myopathy (AQM). In contrast, muscle retains normal electrical
      excitability in peripheral neuropathy. To study the relationship between muscle
      electrical excitability and all types of flaccid weakness occurring in the
      intensive care unit, we identified 14 critically ill, weak patients and measured
      the amplitude of compound muscle action potentials (CMAPs) obtained with direct
      muscle stimulation (dmCMAP) and with nerve stimulation (neCMAP). In 11 of 14
      patients dmCMAP amplitudes were reduced and the ratio of the neCMAP amplitude to
      the dmCMAP amplitude (nerve/muscle ratio) was indicative of loss of muscle
      electrical excitability. In 2 other patients, the nerve/muscle ratio indicated
      neuropathy. Direct muscle stimulation may allow differentiation of AQM from
      neuropathy even in comatose or encephalopathic critically ill patients. AQM may
      be more common than has previously been appreciated.

PMID- 9149069
TI  - Pruritus in chronic hepatitis C: association with high serum bile acids, advanced
      pathology, and bile duct abnormalities.
AB  - Pruritus is a common symptom of chronic cholestatic liver diseases but is
      considered rare in chronic hepatitis. We observed pruritus to be an unusually
      common complaint in patients with advanced chronic hepatitis C. We reviewed the
      records of 175 chronic hepatitis C patients to identify patients with severe,
      diffuse, unexplained pruritus; 12 consecutive prospective patients undergoing
      liver biopsy for chronic hepatitis C served as controls. Assessment included
      laboratory biochemical tests and assessment of liver pathology by stage, grade,
      hepatic activity index, and a bile duct score. Pruritus was present in nine
      (5.1%) patients. Serum AST, ALT, alkaline phosphatase, GGTP, total bilirubin, and
      ferritin were similar in pruritics and controls. Pruritics had higher serum bile
      acids (2028.4 +/- 223.1 mmol/liter vs 423.1 +/- 194.3, P < 0.001), higher
      transferrin saturation (57.5 +/- 6.8% vs 33.2 +/- 3.3, P < 0.01), and lower HCV
      RNA by bDNA (24.5 +/- 12.7 x 10(5) vs 172.7 +/- 54.1 x 10(5), P < 0.05).
      Pathology revealed cirrhosis in 6/9 (66.6%) pruritics vs 1/12 (8.3%) controls (P
      < 0.01). Pruritics had higher pathologic stage (3.7 +/- 0.2 vs 2.2 +/- 0.4, P <
      0.01), grade (4.4 +/- 0.2 vs 2.1 +/- 0.2, P < 0.001), activity index (14.3 +/-
      1.9 vs 8.6 +/- 1.9, P < 0.025), and bile duct score (7.6 +/- 0.6 vs 4.7 +/- 0.4,
      P < 0.01). Of eight pruritics treated with IFN-alpha2b, two had complete ALT
      response and one relapsed. Pruritus followed a relapsing course and only three
      patients partially responded despite a variety of interventions. In conclusion,
      pruritus is a common complication of advanced CHC. Its presence is associated
      with high serum bile acids, advanced pathology and bile duct abnormalities. The
      clinical course of pruritus is relapsing and response to therapy is inconsistent.
      These features suggest that pruritus in CHC has a pathogenesis that may vary from
      that of chronic cholestatic diseases.

PMID- 9149073
TI  - Long-term follow-up of Lambert-Eaton syndrome treated with intravenous
      immunoglobulin.
AB  - Recent reports have shown that patients with Lambert-Eaton myasthenic syndrome
      (LEMS) improve transiently after high-dose intravenous immunoglobulin (IVIG)
      administration. Information about the usefulness of IVIG for long-term treatment
      is rather scanty. Our findings demonstrate the efficacy of monthly IVIG courses
      at a dose of 0.4 g/kg/day for 5 days, in a 41-year-old patient with LEMS without
      detectable malignancy. Improvement in limb strength, peak expiratory flow rate,
      and electrophysiological parameters, as well as clinical signs following IVIG,
      was evident as early as 7 days after the first course and is still maintained at
      24-months follow-up.

PMID- 9149074
TI  - Age-related changes in motor unit function.
AB  - This review focuses on the functional relationship between age-related
      morphological and physiological changes at the level of the motor unit (MU). It
      is well established that older humans are weaker than younger people, exhibit
      reduced force control, and have slower neuromuscular contractile properties.
      Older people may also exhibit a decrease in MU discharge rate, and an increase in
      variability of MU discharge at high force levels. The matching of MU discharge
      and contractile properties may be an age-related neurophysiological strategy
      adopted to optimize motor control, similar to that observed in acute conditions
      such as fatigue. Because muscle force output is modulated partially by MU
      discharge behavior, the study of these properties may offer insights into the
      physiology of muscular weakness and motor function in older people. In turn, this
      will allow the implementation of optimal exercise and rehabilitation programs to
      reduce the degree of dependence associated with aging.

PMID- 9149076
TI  - Single-fiber electromyography, nerve conduction studies, and conventional
      electromyography in patients with critical-illness polyneuropathy: evidence for a
      lesion of terminal motor axons.
AB  - Nine patients at risk for critical illness polyneuropathy (CIP) were included in
      a prospective study. We performed nerve conduction studies, electromyography, and
      a stimulation single-fiber electromyography (SFEMG). Five of 9 patients were
      diagnosed as CIP because they developed abnormal spontaneous activity during the
      follow-up period. Their SFEMG revealed a significant increase in mean jitter
      (25%, P < 0.005). In 4 patients without abnormal spontaneous activity there was
      no significant increase in the mean jitter, although 1 of the latter 4 patients
      showed an increased jitter, indicating that abnormal SFEMG may precede abnormal
      spontaneous activity. Nerve conduction studies did not show any significant
      changes in both patient groups. Our findings suggest that CIP is a primarily
      axonal motor neuropathy. The increased jitter in patients with CIP indicates that
      CIP is a primarily axonal neuropathy with a lesion of terminal motor axons.

PMID- 9149075
TI  - Reliability of maximal voluntary isometric contraction testing in a multicenter
      study of patients with amyotrophic lateral sclerosis. Syntex/Synergen
      Neuroscience Joint Venture rhCNTF ALS Study Group.
AB  - Maximal voluntary isometric contraction (MVIC) is becoming widely used for
      monitoring disease progression in amyotrophic lateral sclerosis (ALS). We
      evaluated the variability of MVIC in a large multicenter (29 sites) drug trial in
      ALS. Intra- and interrater variability were assessed twice during the 19-month
      study. Intrarater reliability increased from the first to the second test,
      approaching the reliability reported for a single experienced clinical evaluator,
      but interrater reliability did not. Multiple clinical evaluators in a single site
      increased the variability of MVIC measurements. Rigorous quality assurance
      standards and monitoring of clinical evaluators should be incorporated into the
      design of multicenter studies using MVIC, since low variability is necessary to
      detect a modest treatment effect.

PMID- 9149077
TI  - Expression of Fas antigen is not associated with apoptosis in human myopathies.
AB  - To determine whether the Fas-Fas-ligand mediated apoptosis occurs in the
      pathologic process of human muscle diseases, we examined the expression of Fas
      antigen, Fas-ligand messenger RNA, and chromosomal DNA fragmentation in the
      muscle cells of patients with a variety of human muscle disorders. The present
      study demonstrated that the Fas antigen of a whole molecule was expressed on the
      muscle fibers of patients with muscle wasting diseases. However, the apoptotic
      process did not occur in the muscle cells, and there was no evidence of Fas
      ligand synthesis in the diseased muscle tissue. Our data suggest that the
      expression of Fas antigen on fibers in diseased muscle is related to unknown
      biological functions other than "apoptosis" in the process of muscle fiber
      injury.

PMID- 9149078
TI  - Depression of human electromyographic activity by fatigue of a synergistic
      muscle.
AB  - In human volunteers, lateral gastrocnemius muscles were stimulated electrically
      under ischemic conditions so as to produce fatigue. Recordings of
      electromyographic (EMG) activity were then made from those muscles and
      simultaneously from untreated medial gastrocnemius muscles during maximal
      voluntary efforts. In the lateral gastrocnemius the mean amount of EMG activity
      declined by 52% and was associated with a 35% reduction in the mean amplitude of
      the M wave (muscle compound action potential) and an insignificant change in M
      wave area. In the medial gastrocnemius the EMG was also diminished, by 29%, but
      there were no significant changes in M-wave amplitude or area. The findings in
      the medial gastrocnemius are consistent with the existence of an inhibitory
      reflex effect which originates in the fatigued lateral gastrocnemius muscle and
      serves to depress excitation in motoneurons supplying that muscle and also in
      those innervating synergists. The inhibitory effect appears to be long-lasting,
      in that a significant reduction of the EMG could still be demonstrated 10 min
      after release of the arterial cuff.

PMID- 9149079
TI  - The effect of autografting on the myosin composition in skeletal muscle fibers.
AB  - The purpose of the study was to investigate the changes in myosin heavy chain
      (MHC) and myosin light chain (MLC) isoforms following autotransplantation of
      extensor digitorum longus muscles. Muscles were grafted in "standard" and "nerve
      intact" conditions. MHC and MLC isoforms were analyzed by sodium dodecyl sulphate
      gel electrophoresis. Changes in MHC isoforms 10, 30, and 60 days after grafting
      were similar in the "standard" and the "nerve-intact" grafts. In contrast to MHC,
      changes in MLC were different in the 10th day groups, but the same in the 30th
      day groups. Sixty days after grafting the content of MLC isoforms was the same as
      the control muscles. These data indicate that transient loss of functional
      innervation, even for a short time, has permanent effect on the composition of
      MHC but not MLC isoforms in regenerating skeletal muscle fibers.

PMID- 9149080
TI  - Dystrophin gene transcripts skipping the mdx mutation.
AB  - The mdx mouse, an animal model used to study Duchenne muscular dystrophy, has a
      nonsense mutation in exon 23 of the dystrophin gene which should result in a
      truncated protein that cannot be correctly localized at the sarcolemma of the
      muscle fibers. Immunohistochemical staining with antidystrophin antibodies has
      shown that while most of the muscle tissue is dystrophin-negative, a small
      percentage of muscle fibers is clearly dystrophin-positive and has somehow
      bypassed the primary nonsense mutation. A sensitive nested polymerase chain
      reaction-based examination of dystrophin gene transcripts around the mdx mutation
      has revealed several alternatively processed transcripts. Four mRNA species
      skipped the mutation in exon 23, were in-frame, and could be translated into a
      shorter but still functional dystrophin protein. Specific tests for these
      transcripts demonstrated these were also present in normal mouse muscle tissue.

PMID- 9149081
TI  - Stimulated single-fiber electromyography in Lambert-Eaton myasthenic syndrome
      before and after 3,4-diaminopyridine.
AB  - A patient with LEMS unrelated to cancer was studied by stimulated single-fiber
      electromyography (SFEMG) before and 3 months after the onset of therapy with 3,4
      diaminopyridine. All end-plates showed a progressive reduction in blockings and
      jitter with the increase in stimulation rate. Treatment significantly corrected
      this feature, but the overall pattern of frequency-improved jitter remained. Such
      widespread finding is rare but diagnostic for Lambert-Eaton myasthenic syndrome.
      Stimulated SFEMG can be used to monitor therapy in such patients.

PMID- 9149082
TI  - Peripheral nerve dysfunction is reflected by loss of ankle reflexes but not by
      autonomic neuropathy in diabetic patients.

PMID- 9149083
TI  - Reinnervation and regeneration of denervated rat soleus muscles.

PMID- 9149084
TI  - Acute infantile weakness: a case of vaccine-associated poliomyelitis.

PMID- 9149085
TI  - Progression of paclitaxel-induced neuropathy following discontinuation of
      treatment.

PMID- 9149086
TI  - Striational autoantibodies in myasthenia gravis mainly react with ryanodine
      receptor.

PMID- 9149087
TI  - Intra-aortic injection of myoblasts in mdx mice: genetic and technetium-99m cell
      labeling and biodistribution.

PMID- 9149088
TI  - Association between internalized nuclei and mitochondrial enzyme defects in
      muscle.

PMID- 9149089
TI  - Acoustic and electrical activities during voluntary isometric contraction of
      biceps brachii muscles in patients with spastic cerebral palsy.

PMID- 9149091
TI  - Nonsystemic vasculitic neuropathy presenting as progressive paraplegia.

PMID- 9149092
TI  - Ultrasound identification of the myofacial trigger point.

PMID- 9149090
TI  - Chronic fatigue syndrome and skeletal muscle mitochondrial function.

PMID- 9149093
TI  - Organization, sequence and functional analysis of a mouse BDNF promoter.
AB  - To examine the content of the 5' flanking region of the mouse BDNF gene a mouse
      library was screened using oligonucleotides corresponding to the rat exon I
      untranslated region. A 6-kb genomic fragment containing exons I and II and
      flanking regions was isolated and sequenced. The structure of the 5' end of the
      mouse gene is similar to that of rat, exons I and II are 2 small untranslated
      regions clustered within 500 bp of each other at the 5' end of the gene. The
      nucleotide sequence homology between rat and mouse is 93%. Analysis for
      transcription factor-binding sites show a predominance of AP1 and C/EBP elements
      which are conserved between the 2 species. Deleted fragments of the 5' flanking
      region of exons I and II were fused to the luciferase reporter gene and
      transcriptional activity was analyzed by transient expression in primary cortico
      hippocampal cultures. We found that a fragment of 266 bp from exon I
      transcription start is sufficient for promoter activity in basal conditions.
      Following experimental stimulation by treatment with kainic acid, we determined
      that regulatory elements responsive to kainic acid are located within 989 bp of
      the transcriptional start of exon I.

PMID- 9149094
TI  - Differential effects of axotomy on the in vivo synthesis of the stress-inducible
      and constitutive 70-kDa heat-shock proteins in rat dorsal root ganglia.
AB  - The purpose of this study was to the test the hypothesis that heat-shock protein
      expression is upregulated (or induced) in dorsal root ganglia (DRG) following
      axotomy. To test this hypothesis, DRG or sciatic nerve (SN) proteins were pulse
      labelled in vivo with [35S]methionine and the metabolic synthesis of two major 70
      kDa heat-shock proteins, the constitutive species (hsc70) and stress-inducible
      species (hsp68), were analyzed by two-dimensional polyacrylamide gel
      electrophoresis (2D-PAGE) and fluorography. Results showed that DRG hsp68
      expression was absent (or barely detectable) under normal (sham-axotomy)
      conditions. However, following long-range axotomy (35 mm from DRG), there was a
      delayed (> 12 h post-axotomy) and transient upregulation of DRG hsp68 metabolic
      synthesis. Control studies demonstrated that, although DRG hsp68 was upregulated,
      hsp68 was not induced in SN regions proximal to the crush site. In contrast to
      DRG hsp68 expression, there was abundant DRG hsc70 synthesis under normal
      conditions that did not significantly change following axotomy. These results
      suggest that a specific stress protein response is induced in DRG following
      axotomy.

PMID- 9149095
TI  - Differential induction of heat shock mRNA in oligodendrocytes, microglia, and
      astrocytes following hyperthermia.
AB  - A time course analysis of hsp70 mRNA induction in response to a physiologically
      relevant increase in body temperature of 2.6 degrees C was performed in the
      rabbit forebrain. A protocol that combined in situ hybridization and
      cytochemistry on the same tissue section was employed to identify reactive glial
      cell types. Cytochemical markers for astrocytes, microglia, and oligodendrocytes
      were utilized in combination with a DIG-labelled hsp70 riboprobe, which permitted
      mRNA localization at high resolution. Four glial cell body-enriched regions of
      the rabbit forebrain were examined, namely, cortical layer 1, hippocampal
      fissure, corpus callosum, and fimbria. Maximal hsp70 mRNA induction was observed
      in 2 and 3 h hyperthermic animals. The colocalization analysis demonstrated that
      hsp70 mRNA was induced in oligodendrocytes and microglia, but not in forebrain
      GFAP positive astrocytes. In addition, cell counts were performed which showed
      that almost all oligodendrocytes induced hsp70 mRNA while a subpopulation of
      microglial cells responded. These data are consistent with the notion that
      oligodendrocytes, microglia, and astrocytes exhibit distinct thresholds for
      activation of the heat shock response following a physiologically relevant
      increase in body temperature.

PMID- 9149096
TI  - N-glycosylation at the conserved sites ensures the expression of properly folded
      functional ACh receptors.
AB  - The role of the conserved carbohydrate moiety in the expression of complete
      acetylcholine receptor (AChR), alpha2 beta gamma delta was re-investigated by
      expressing additional site-directed mutant subunits, lacking an N-glycosylation
      site, in Xenopus oocytes. All mutant subunits were stably expressed and appeared
      to associate with other normal subunits; however, removal of carbohydrate on the
      alpha subunit inhibited the formation of 125I-alpha-bungarotoxin (alpha-BuTX)
      binding sites and functional ACh-gated ion channels. 125I-alpha-BuTX binding to
      AChRs was also significantly reduced by removal of the conserved carbohydrate on
      the gamma or delta subunits. Immunoprecipitation with monoclonal antibodies that
      recognize the two distinct alpha-BuTX sites on the AChR indicated that the mutant
      gamma subunit did not interfere with efficient formation of the alpha-BuTX
      binding site at the alpha/delta interface, but loss of the carbohydrate did
      interfere with formation of the alpha-BuTX binding site at the alpha/mutant gamma
      interface. A similar result was obtained with the mutant delta subunit.
      Furthermore, the mutant gamma and mutant delta subunits were not incorporated
      efficiently into the mature (correct tertiary conformation capable of alpha-BuTX
      binding) alpha beta delta or alpha beta gamma complexes, respectively. Since both
      mutant gamma and mutant delta subunits were capable of assembling with the alpha
      subunits (immature assembly), these results suggest that the formation of the two
      alpha-BuTX binding sites requires correct folding of the alpha gamma and alpha
      delta complexes, which is aided by the conserved carbohydrate on the gamma and
      delta subunits. Electrophysiological experiments demonstrated that functional
      receptors containing mutant subunits were produced, but the functional properties
      of the mutant receptors were differentially altered, depending on the subunit
      mutated. Together, our results suggest that N-glycosylation of AChR subunits
      ensures the correct folding of important functional domains and expression of
      proper functional receptors in the plasma membrane.

PMID- 9149097
TI  - Seizure-induced alterations of plasma membrane calcium ATPase isoforms 1, 2 and 3
      mRNA and protein in rat hippocampus.
AB  - Improper intracellular regulation of the ubiquitous second messenger, calcium,
      has been linked to several pathological conditions. The plasma membrane calcium
      ATPase (PMCA) is one of the primary systems for translocating calcium from the
      cytosol to the extracellular milieu. As an initial assessment of the possible
      involvement of PMCAs in kainate (KA)-induced neurodegeneration, we have
      determined the effect of KA-induced seizures upon PMCA mRNA and protein. In situ
      hybridization was performed on tissue from adult male Sprague-Dawley rats
      sacrificed at various time points following i.p. injection of KA. KA altered the
      expression within the hippocampal subfields for mRNAs of PMCA isoforms 1 and 2.
      PMCA 1 and 2 mRNAs exhibited hybridization below control levels 12-48 h post
      injection within CA1 and CA3. Within the dentate gyrus, PMCA 2 mRNA hybridized
      below control levels 4 h post-injection, but recovered to control levels by 24 h
      post-injection. Alterations in combined PMCA protein levels occurred at all time
      points examined post-injection. These observations provide evidence that KA
      induced seizures alter the PMCAs at the mRNA and protein levels, suggesting a
      possible role for this calcium efflux system in the neuronal degeneration
      inherent to this paradigm.

PMID- 9149098
TI  - Differential expression of c-fos, Hsp70 and Hsp27 after photothrombotic injury in
      the rat brain.
AB  - In situ hybridization and immunohistochemistry were used to examine the
      expression of c-fos, Hsp70 and Hsp27 following photothrombotic injury in the
      right fronto-parietal cortex of the rat. C-fos mRNA and protein were detected in
      the entire cerebral cortex on the lesioned side. Hsp70 mRNA accumulation was
      observed only adjacent and peripheral to the site of the lesion. At 1 h after
      photothrombotic injury, Hsp70 expression delineates the area of necrosis at 24 h
      after photothrombotic injury. Hsp27 protein was observed in the ipsilateral
      cerebral cortex with the exception of the deep layers of the cingulate cortex. In
      addition, while c-Fos immunoreactivity was localized in cell nuclei, Hsp27
      immunoreactivity was detected in the cytoplasm of astrocytes. These results
      demonstrate that unilateral cortical injury induces changes in gene expression
      that vary according to cell type and brain region.

PMID- 9149099
TI  - Comparison of tissue distribution of two novel serine/threonine kinase genes
      containing the LIM motif (LIMK-1 and LIMK-2) in the developing rat.
AB  - We previously isolated two novel serine/threonine kinase genes containing the LIM
      motif (LIMK-1 and LIMK-2) from a rat cDNA library. To examine the functions of
      these genes, we performed in situ hybridization in the developing rat nervous
      system. LIMK-1 and LIMK-2 mRNAs mostly co-localized during development and are
      expressed preferentially in the central nervous system during mid-to-late
      gestation but the signals decreased during the post-natal period. However,
      differential gene expression was observed in some nuclei in the CNS; LIMK-1 mRNA
      was intensely expressed in the facial motor nucleus, the hypoglossal nucleus,
      deep nuclei of the cerebellum and the layers 3, 5 and 6 of the adult cerebral
      cortex while only LIMK-2 mRNA was preferentially expressed in the some parts of
      the epithelium. In the nasal cavity, LIMK-1 and LIMK-2 mRNAs were expressed
      complementarily. Our results suggest that LIMK-1 and LIMK-2 may have different
      functions in these regions during development.

PMID- 9149101
TI  - Differential expression patterns of GABA transporters (GAT1-3) in the rat
      olfactory bulb.
AB  - The localization of GABA transporters 1-3 (GAT1-3) was investigated in the rat
      olfactory bulb by using in situ hybridization and immunohistochemistry. In the
      glomerular and the internal granular layers, GAT1 mRNA was expressed in most of
      periglomerular and granule cells, which are known to be GABAergic. In addition,
      we compared GAT1 mRNA expression with that of glutamic acid decarboxylase67
      (GAD67) mRNA. The expressions were very similar in these two layers, indicating
      that GAT1 mRNA is mainly expressed in GABAergic neurons. However, in the external
      plexiform and the olfactory nerve layers, we observed more GAT1 mRNA-positive
      cells than GAD67 ones, suggesting that GAT1 mRNA is also expressed in non
      GABAergic neurons and in glial cells. GAT3 mRNA expression was observed in small
      glial-like cells which might be involved in GABAergic neurotransmission
      throughout the olfactory bulb. This was confirmed by double-immunostaining
      studies which showed the expression of both GAT3 and glial fibrillary acidic
      protein (GFAP) mRNAs in astrocytes. Moreover, GAT2 mRNA was expressed only in the
      ependyma and arachnoid. These findings suggest that the expression patterns of
      GABA transporters differ with the type of cells in the rat olfactory bulb where
      GAT1 and GAT3 may play an imporatant role in GABA-mediated transmission, such as
      lateral inhibition.

PMID- 9149100
TI  - 1,25-Dihydroxyvitamin D3 inhibits the expression of inducible nitric oxide
      synthase in rat central nervous system during experimental allergic
      encephalomyelitis.
AB  - The inducible form of nitric oxide synthase (iNOS) generates nitric oxide of
      which the excessive production is associated with central nervous system (CNS)
      inflammatory diseases. The investigation of iNOS expression during experimental
      allergic encephalomyelitis (EAE) of the Lewis rat demonstrated iNOS
      immunoreactivity and mRNA both during inflammatory bursts (days 12 and 23 post
      immunization) and during the remission phase (day 18). iNOS expression was region
      specific and expanded with time along a caudo-rostral axis, thus, correlating
      with the development of inflammatory infiltrates. Whereas cells of the
      monocyte/macrophage lineage continuously contributed to iNOS expression,
      astrocytes only expressed iNOS immunoreactivity or mRNA during the relapse (day
      23). In order to investigate possible regulatory effects of 1,25-dihydroxyvitamin
      D3 (1,25-D3) on iNOS expression, rats were treated with the hormone after the
      beginning of clinical signs (days 11, 13, 19, 21 and 23 post-immunization), and
      areas of the CNS were examined at day 23. 1,25-D3 exerted a drastic inhibitory
      effect on iNOS expression, both at the protein and the mRNA levels. However, this
      effect was region-specific, and was most pronounced in the cerebellum and
      brainstem, but non-existent in cerebral cortex. iNOS down-regulation occurred in
      macrophages, activated microglia and astrocytes. The inhibition of iNOS
      expression in some CNS structures could account for the improvement of clinical
      signs observed in EAE-rats treated with 1,25-D3. Since 1,25-D3 can be synthesized
      by activated macrophages or microglia, our results support the hypothesis that
      this hormone might be implicated in the control of the CNS-specific immune
      responses. 1,25-D3 or its analogues could, thus, be of therapeutic value in the
      management of iNOS-associated diseases of the CNS.

PMID- 9149102
TI  - Effect of chronic antipsychotic drug treatment on preprosomatostatin and
      preprotachykinin A mRNA levels in the medial prefrontal cortex, the nucleus
      accumbens and the caudate putamen of the rat.
AB  - In situ hybridization histochemistry was used to study the expression of
      preprosomatostatin (PPSOM) and preprotachykinin A (PPT-A) mRNA in the medial
      prefrontal cortex (mPFC), the nucleus accumbens (NAC) and the caudate putamen
      (CP) of the rat after chronic (21 days) treatment with the classical
      antipsychotic drug haloperidol (1 mg/kg i.p.), the atypical antipsychotic drugs
      clozapine (15 mg/kg i.p.) and amperozide (5 mg/kg i.p.), and the selective
      dopamine (DA)-D2/D3 receptor antagonist raclopride (2 mg/kg i.p.). Whereas
      amperozide markedly elevated the numerical density of PPSOM mRNA expressing
      neurons in the mPFC (52%), the other drugs did not significantly affect PPSOM
      mRNA levels in any of the brain regions studied. Amperozide also altered PPT-A
      mRNA expression in the mPFC, i.e. a decrease (22%) was found. Of the other drugs
      tested only haloperidol significantly decreased PPT-A mRNA levels in the NAC
      shell (14%), in the dorso-lateral CP (19%) and in the medial CP (15%). In view of
      the differences between amperozide and the other drugs studied, as regards both
      pre-clinical and clinical characteristics, we suggest that the specific effects
      of amperozide on PPSOM and PPT-A mRNA in the mPFC may be related to its 5-HT
      releasing action in the frontal cortex, an effect possibly caused by its alpha2
      adrenoceptor blocking activity. This effect, in turn, may be related to an
      antidepressant-like action that this compound exhibits in animal studies. The
      decrease in PPT-A mRNA levels seen after the haloperidol treatment is probably
      due to its potent DA-D2 receptor antagonism and may be related to side-effects,
      rather than therapeutic effects of this drug.

PMID- 9149103
TI  - Localization of a 42-kDa inositol 1,3,4,5-tetrakisphosphate receptor protein in
      retina and change in expression after optic nerve injury.
AB  - The mRNA and protein expression of a 42-kDa inositol 1,3,4,5-tetrakisphosphate
      receptor (InsP4R) was investigated in cryostat and paraffin sections from rat,
      porcine and bovine retina. InsP4R mRNA was localized by in situ hybridization in
      the ganglion cell layer, the inner nuclear cell layer and the outermost part of
      the outer nuclear cell layer. For immunocytochemistry, we used an antibody raised
      against a 19-amino-acid peptide (peptide-3) derived from previous microsequencing
      of proteolytic fragments of the porcine InsP4R (Stricker et al., FEBS Lett., 370
      (1995) 236). The distribution of immunoreactivity was similar in all species
      investigated. Two cell types, most likely wide-field amacrine and retinal
      ganglion cells, were intensely stained. Prominent immunoreactivity in the on/off
      sublaminae of the inner plexiform layer and in the optic nerve layer indicates a
      pre- and/or post-synaptic localization of the protein. Moreover, significant
      InsP4R protein expression in the inner segment of photoreceptors points to a
      putative role of the second messenger InsP4 in signaling processes related to
      phototransduction. However, also the endfeet of Muller glia cells in the optic
      nerve layer were intensely stained. Optic nerve crush caused only minor changes
      in retinal InsP4R mRNA levels whereas InsP4R immunoreactivity was attenuated for
      more than 4 weeks in the photoreceptor inner segments, wide-field amacrine cells,
      and in retinal ganglion cells. The immunopositive sublaminae of the inner
      plexiform layer appeared to have shrunken. However, the signal intensity
      gradually recovered after 10 weeks. Since in parallel sections stained with a
      monoclonal antibody directed against the vesicular protein synaptophysin no
      changes were found, the alterations in InsP4R immunoreactivity induced by nerve
      injury are not due to a general decline in the expression of pre-synaptic
      proteins. We, therefore, hypothesize that the InsP4R might be linked to altered
      intracellular Ca2+ signaling after neuronal injury.

PMID- 9149105
TI  - Differential distribution of synapsin IIa and IIb mRNAs in various brain
      structures and the effect of chronic morphine administration on the regional
      expression of these isoforms.
AB  - Quantitative reverse transcriptase-polymerase chain reaction and in situ
      hybridization techniques were used to determine the regional distribution of
      synapsin IIa and IIb mRNAs in rat central nervous system and to assess the effect
      of chronic morphine administration on the gene expression of these two isoforms
      of synapsin II. These isoforms are members of a family of neuron-specific
      phosphoproteins thought to be involved in the regulation of neurotransmitter
      release. Our data demonstrate the widespread distribution, yet regionally
      variable expression, of synapsin IIa and IIb mRNAs throughout the adult rat brain
      and spinal cord. The ratios of the relative abundance of synapsins IIa and IIb
      differed by up to 4.5-fold among the various regions studied. Synapsin IIa and
      IIb mRNAs were shown to be highly concentrated in the thalamus and in the
      hippocampus, whereas lower concentrations were found in most other central
      nervous system structures. In this study, we show differential regulation by
      morphine of synapsins IIa and IIb in various regions of the brain. In the
      striatum, a 2.4-fold increase was observed in the levels of synapsin IIa mRNA
      following chronic morphine regime, whereas no change was found for synapsin IIb.
      On the other hand, mRNA levels of synapsin IIb in spinal cord of chronically
      treated rats were markedly decreased (by 62%), while no alterations were observed
      in synapsin IIa. Selective regulation by morphine has also been demonstrated in
      several other central nervous system structures. The opiate-induced regulation of
      the gene expression of synapsin II isoforms could be viewed as one of the
      cellular adaptations to the persistent opiate effects and may be involved in the
      molecular mechanism underlying opiate tolerance and/or dependence.

PMID- 9149104
TI  - Evidence that carbon monoxide stimulates prostaglandin endoperoxide synthase
      activity in rat hypothalamic explants and in primary cultures of rat hypothalamic
      astrocytes.
AB  - Carbon monoxide (CO) shares with nitric oxide (NO) the ability to modulate the
      release of hypophysiotropic peptides from rat hypothalamic explants. While both
      gases are believed to act as neural messengers in the brain via the activation of
      soluble guanylyl cyclase, the latter is almost undetectable in the rat
      hypothalamus. NO has been shown to exert some of its biological actions through
      the modulation of prostaglandin endoperoxide synthase (PGHS) activity. We have,
      therefore, investigated whether CO also can use PGHS as a signaling pathway in
      the hypothalamus. Endogenous CO is produced in equimolar amounts with biliverdin
      (BV) by the catabolism of hemin through heme oxygenase (HO). Hemin, two
      inhibitors of HO, zinc-protoporphyrin-9 (ZnPP9) and tin-mesoporphyrin-9 (SnMP9),
      ferrous hemoglobin (Hb), indomethacin and dexamethasone (DEX) were used as
      pharmacological tools. Prostaglandin E2 (PGE2) released from rat hypothalamic
      explants or primary cultures of hypothalamic astrocytes was taken as a marker of
      PGHS activity. It was found that: (1) hemin evokes an increase in PGE2 release
      from hypothalamic explants; (2) this effect is counteracted by ZnPP9, SnMP9, Hb
      and indomethacin; (3) the metallo-porphyrins and indomethacin, but not Hb, are
      also able to inhibit basal PGE2 release from hypothalamic explants; and (4)
      dexamethasone does not inhibit, and even potentiates, the stimulatory effect of
      hemin on PGE2 release from hypothalamic astrocytes. The evidence presented here
      suggests that the catabolism of endogenous or exogenously added hemin is
      associated with an increase in PGE2 production in the rat hypothalamus. This
      effect can be attributed to the formation of CO, since the other end-product of
      HO, BV, does not enhance PGE2 release. Thus, at least some of the biological
      effects of CO at the hypothalamic level might be mediated by the activation of
      the PGHS pathway.

PMID- 9149106
TI  - Long-lasting enhancement of ACh receptor currents by lysophospholipids.
AB  - Lysophosphatidylcholine (LysoPtdCho) and lysophosphatidylethanolamine
      (LysoPtdEtn), which are formed by phospholipase A2-catalyzed hydrolysis of
      phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn), respectively,
      are proposed to be involved in protein kinase C (PKC) activation. Their
      physiological significance, however, remains unclear. We examined the effects of
      lysoPtdCho and lysoPtdEtn on acetylcholine (ACh) receptor currents using oocytes
      expressing Torpedo nicotinic ACh receptors. LysoPtdCho enhanced the currents in a
      washing time- and dose-dependent manner (10 nM-1 microM), reaching a maximum of
      191% at 20 min after treatment. The currents were enhanced to a lesser extent at
      higher concentrations, and instead, inhibited to 81% at 10 microM. Likewise,
      lysoPtdEtn also potentiated the currents to 200% at 10 microM, although its dose
      dependent curve shifted to right as compared with that of lysoPtdCho. The current
      potentiation was blocked by a PKC inhibitor, PKC inhibitor peptide (PKCI), or
      removal of extracellular Ca2+. In addition, lysoPtdCho and lysoPtdEtn enhanced
      the currents in mutant ACh receptors lacking PKC phosphorylation sites on the
      alpha and delta subunits. These results suggest that lysophospholipids such as
      lysoPtdCho and lysoPtdEtn potentiated ACh receptor currents by Ca2+-dependent PKC
      activation, but that this effect did not require PKC phosphorylation of the ACh
      receptor.

PMID- 9149107
TI  - Diurnal expression of recoverin in the rat retina.
AB  - The levels of expression of recoverin mRNA and protein was examined during a 24-h
      period in the rat retina. Northern blot analysis revealed that rat recoverin mRNA
      expression was consistently high during the light period, then decreased after
      onset of darkness, and gradually increased later during the dark period. The
      cyclic rhythm in recoverin protein expression was consistent with the cyclic
      rhythm in recoverin mRNA expression, insofar as recoverin mRNA and protein levels
      were lowest soon after lights off, and there was an increase in expression late
      in the dark period. These observations suggest that the rate of recoverin
      transcription may occur maximally during the period of greatest exposure to
      light, presumably when it is most needed by the photoreceptor to fulfill its role
      in visual transduction, then decreases at night, when high levels of expression
      are not required.

PMID- 9149108
TI  - Expression of adenylyl cyclase type I in cochlear inner hair cells.
AB  - Expression of calcium/calmodulin-activated adenylyl cyclase type I (ACI) mRNA has
      been determined in the cochlea and in an organ-of-Corti subdissected tissue
      fraction by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis.
      Amplification products of predicted size were obtained from the mouse cochlea and
      rat organ of Corti with nucleotide sequences corresponding to respective ACI
      brain transcripts. In addition, ACI template was detected in a rat inner hair
      cell cDNA library by PCR. Immunoreactivity to ACI has been localized within the
      organ of Corti to the inner hair cell, with diaminobenzidine staining found in
      both the cell body and in the stereocilia. Evidence, thus, has been obtained that
      both ACI transcript and protein are expressed in the inner hair cell, the primary
      mechanosensory receptor cell of the cochlea. We hypothesize that ACI is activated
      by calcium influx through a calcium/calmodulin interaction and that this adenytyl
      cyclase isoform may have a role in modulation of receptoneural afferent
      transmission and/or mechanosensory transduction in the cochlea.

PMID- 9149109
TI  - Coincident induction of K rev-1/rap 1A, rap 1B and H-ras mRNAs in the rat spinal
      cord by noxious stimulation.
AB  - Two cDNA fragments, K rev-1/rap 1A and rap 1B, were amplified from total cellular
      RNA of the rat spinal cord by reverse transcription-polymerase chain reaction
      with a set of oligonucleotide primers specific for the human rap 1A cDNA. We
      report here using Northern blot analysis with these cDNA probes that noxious
      stimulation causes a marked and coincident increase in rap 1A, rap 1B and H-ras
      mRNAs in the rat spinal cord. This suggests that Rap 1 participates in sensory
      processing in spinal neurons in parallel with Ras.

PMID- 9149110
TI  - Up-regulation of D3 dopamine receptor mRNA in the nucleus accumbens of human
      cocaine fatalities.
AB  - The effects of chronic cocaine use on D3 receptor mRNA expression in the human
      nucleus accumbens was assessed by reverse transcription-polymerase chain
      reaction. D3 receptor/cyclophilin mRNA ratios in the nucleus accumbens were
      increased 6-fold in cocaine overdose victims as compared to age-matched and drug
      free control subjects. This finding demonstrates that chronic cocaine exposure
      leads to adaptive increases in the expression of D3 receptor mRNA in a critical
      reward center in brain.

PMID- 9149111
TI  - Estrogen inhibits hypothalamic pro-opiomelanocortin gene expression in
      hypothalamic neuronal cultures.
AB  - Many in vitro studies show estrogen regulation of the hypothalamic pro
      opiomelanocortin (POMC) system, including a decrease in hypothalamic POMC mRNA
      after estradiol treatment. Because such in vivo experiments do not allow one to
      determine whether peripheral, interacting systems or extra-hypothalamic brain
      regions are involved in this regulation, we sought to establish whether estrogen
      acts directly in hypothalamus to decrease POMC mRNA. Using an in vitro approach,
      we studied effects of estradiol (E2) on POMC/cyclophilin mRNA concentrations
      (RNAse protection assays) in neuronal cultures derived from day 17 fetal rat
      hypothalamus. Chemically defined medium was deprived of progesterone for 2 days
      prior to E2 treatment and for the duration of the study. E2 (10(-13)-10(-9) M)
      dose-dependently decreased POMC mRNA concentrations during a 2-day treatment.
      Whereas the lowest dose (10(-13) M) of E2 resulted in a statistically significant
      44% decrease in POMC mRNA concentrations relative to control cultures, this
      inhibitory effect was lost because higher doses (10(-11) and 10(-9) M) did not
      produce statistically significant decrements (22 and 16%, respectively) in POMC
      mRNA concentrations. Additional time course studies revealed that this decrease
      in POMC mRNA can be seen as early as 4 h after E2 (10(-13) M) treatment. We
      conclude that E2 inhibition of POMC mRNA concentrations in hypothalamic neuronal
      cultures indicates that this inhibition can occur directly in hypothalamus.

PMID- 9149112
TI  - Rat tyrosine hydroxylase gene polymorphisms.
AB  - The rat tyrosine hydroxylase gene (TH) from a panel of outbred and inbred rat
      strains has been analysed by Southern blotting, restriction-endonuclease mapping
      and direct sequencing of PCR-amplified products for detecting DNA polymorphisms.
      Five polymorphic sites have been characterized. This information may be used in
      pharmacogenetic studies to determine the influence of the TH gene in animal
      models of affective disorders and addictive behaviours.

PMID- 9149113
TI  - Localization of gene expression for phosphatidylinositol transfer protein in the
      brain of developing and mature rats.
AB  - Gene expression for alpha- and beta-isoforms of phosphatidylinositol transfer
      protein (PITP) was examined using in situ hybridization histochemistry in
      developing and mature rat brains. During embryonic and early post-natal stages,
      gene expression for both PITP-alpha and -beta were detected widely throughout the
      entire neuraxis. In the adult brain, the expression for PITP-alpha was positive
      in almost all neurons throughout the entire brain while the expression for PITP
      beta markedly decreased in the entire gray matter regions except for the
      cerebellar cortex. By comparison with the previous findings on the expression for
      various molecules involved in the PI turnover, the present finding suggests that
      PITP is involved more intimately in some differentiation-related functions of
      immature neurons than those of mature neurons in co-operation with PI-related
      molecules and that PITPs exert their functions in adult brain in concert with
      PLCs in subtype-preferable inter-relation.

PMID- 9149114
TI  - Isolation of the gene encoding lamp-1, a lysosomal membrane protein, by
      differential screening in an animal model of status epilepticus.
AB  - The present study employed differential library screening to identify genes
      associated with kainic acid (KA)-mediated selective neuronal death. One of the
      isolated clones was lamp-1, which encodes a major lysosomal membrane protein that
      is also present in the cell membrane. Following systemic KA treatment, lamp-1 was
      induced in vulnerable hippocampal and other limbic regions. This effect was
      blocked by cycloheximide (CHX) pre-treatment. Northern blot analysis also
      demonstrated the presence of lamp-1 transcripts in non-neural tissues. These
      findings suggest a novel role for lysosomal membrane proteins as markers of
      selective neuronal vulnerability.

PMID- 9149115
TI  - Protective effect of food additives on aflatoxin-induced mutagenicity and
      hepatocarcinogenicity.
AB  - Food additives such as turmeric (Curcuma longa), and active ingredient curcumin
      (diferuloyl methane), asafoetida (flavouring agent), butylated hydroxyanisole
      (BHA), butylated hydroxytoluene (BHT) and ellagic acid were found to inhibit the
      mutagenesis induced by aflatoxin B1 (AFB1) (0.5 microg/plate) in Salmonella
      tester strains TA 98 and TA 100. Turmeric and curcumin, which were the most
      active, inhibited mutation frequency by more than 80% at concentrations of 2
      microg/plate. Other food additives were also significantly effective. Dietary
      administration of turmeric (0.05%), garlic (0.25%), curcumin and ellagic acid
      (0.005% each) to rats significantly reduced the number of gammaglutamyl
      transpeptidase-positive foci induced by AFB1 which is considered as the precursor
      of hepatocellular neoplasm. These results indicate the usefulness of antioxidant
      food additives in ameliorating aflatoxin-induced mutagenicity and
      carcinogenicity.

PMID- 9149116
TI  - Expression of androgen receptor and its implication in hepatoma cells.
AB  - Hepatocellular carcinoma (HCC) in human and murine has been known to occur more
      frequently in male than female. Attempts have been made to find a possible
      mechanism of increased growth advantage in the HCC cells by testosterone (T).
      Treatment of HepG2 human HCC cells with T increased DNA synthesis by 30-50%,
      whereas T increased it by 10-30% in FaO (rat) cells. Androgen receptor (AR)
      levels in HepG2 and FaO cells were 94.1 fmol/mg protein and 55.0 fmol/mg protein,
      respectively. Expression of AR mRNA species was detected as about 10 kb (doublet)
      in HepG2. On the other hand, much less expression of AR mRNA was observed in FaO
      cells. AR signals around 28S rRNA (4.7 kb) and the small size RNAs detected in
      the total cellular RNAs were not found in the poly(A) + RNAs isolated from the
      cells. Contrary to the earlier observation by other investigators, expression of
      hepatic AR was not down-regulated by T until 72 h of treatment. These results
      demonstrate one of the modes of action by T for the preferential development of
      HCC in male.

PMID- 9149117
TI  - Cadmium-induced 8-hydroxydeoxyguanosine formation, DNA strand breaks and
      antioxidant enzyme activities in lymphoblastoid cells.
AB  - The effect of cadmium ion (Cd) and ascorbic acid (Asc) on the induction of
      oxidative DNA damage and on the activities of antioxidant enzymes were
      investigated in human lymphoblastoid cells (AHH-1 TK+/-). Cd at low
      concentrations of 5-35 microM induced the formation of 8-hydroxy-2'
      deoxyguanosine (8-OHdG) and caused nuclear DNA strand breaks. The formation both
      of 8-OHdG and of DNA strand breaks was dose-dependent at the low Cd
      concentration; both parameters were linearly correlated with each other (R =
      0.932 and P = 0.0209). 8-OHdG formation by Cd plateaued at a Cd concentration of
      50 microM. Asc also induced 8-OHdG formation, but it had no synergistic effect
      with Cd on the formation of 8-OHdG or DNA strand breaks. Cd at the concentration
      of 50 microM induced the nuclear activity of the antioxidant enzymes, catalase
      and superoxide dismutase (SOD). Furthermore, Cd caused a decrease in the
      concentration of reduced glutathione (GSH) and an increase in concentration of
      the oxidized form (GSSG). While Asc had no observable effect on SOD activity, it
      did increase nuclear catalase activity in cells. This effect on catalase was
      synergistic with that of Cd. The linear correlation between 8-OHdG and DNA strand
      breaks induced by Cd at the lower Cd concentrations (< or = 50 microM), suggested
      that the extent of formation of DNA strand breaks induced by Cd may be offset by
      their induction of the formation of 8-OHdG and antioxidant enzyme activities.

PMID- 9149119
TI  - Frequent loss of heterozygosity of chromosome 3 short arm detected by PCR-based
      microsatellite polymorphisms in cervical squamous cell carcinoma.
AB  - Karyotypic studies have shown that genetic aberrations of the short arm of
      chromosome 3 (3p) may be involved in the pathogenesis of cervical carcinoma. In
      this study we analyzed nine polymorphic microsatellite repeats on 3p using a PCR
      based assay for loss of heterozygosity (LOH) in 64 invasive squamous cell
      carcinomas of the cervix. These markers encompass chromosome region 3p13-25. LOH
      at one or more loci was detected in 46 (79%) out of the 58 informative cases. The
      incidence of LOH at locus D3S643 (3p13) was the highest among nine markers
      examined. The difference between the frequency of LOH at D3S643 in early stage (I
      II) disease (43%) and those with advanced stage (stage III-IV) (79%) was
      statistically significant (P < 0.05). The results indicate that tumor suppressor
      gene(s) that play a role in cervical cancer may be located on the short arm of
      chromosome 3, likely near or at 3p13. The LOH at 3p13 appears to be a late event
      in tumor progression and may serve as an indicator for a less favorable clinical
      outcome.

PMID- 9149118
TI  - Emergence of osteoblast-like cells in a neoplastic human salivary cancer cell
      line after treatment with 22-oxa-1alpha, 25-dihydroxyvitamin D3.
AB  - A neoplastic clonal cell line, which was prepared by 5-azacytidine treatment of a
      neoplastic human salivary intercalated duct cell line, was cultivated in the
      presence of 22-oxa-1alpha, 25-dihydroxyvitamin D3 and 3 mM beta-glycerophosphate.
      Major alterations, such as expression of type I collagen and alkaline phosphatase
      as well as of human osteopontin and osteonectin, were observed in these cells
      with a phenotype similar to osteoblasts. In addition, formation of bone nodule
      was observed in the cultured cells. The tumors produced by transplantation into
      nude mice of the clonal cells were treated with 22-oxa-1alpha, 25
      dihydroxyvitamin D3 and examined for tumor growth and morphology. Consequently,
      growth of the treated tumor was significantly suppressed. Moreover, it was found
      that bone formation was induced in the treated tumor, in which the tumor cells
      around bone formation expressed human osteopontin and osteonectin mRNA as could
      be detected by in situ hybridization. The above findings indicate that the
      emergence of osteoblast-like cells in the human salivary cancer cells occurs in
      the presence of 22-oxa-1alpha, 25-dihydroxyvitamin D3 and beta-glycerophosphate.

PMID- 9149120
TI  - The timing of insulin/c-Ras signal is critical for its effect upon the
      differentiation of C3H10T1/2-derived preadipocytes.
AB  - The effect of the peptide hormone insulin upon the differentiation of a 10T1/2
      derived preadipocytic line was found to display a potent time-dependence. Insulin
      addition before cell confluence strongly enhanced differentiation, while addition
      after confluence had no effect. In keeping with the role of c-Ras as a downstream
      effector of insulin, c-ras downregulation before confluence abolished
      differentiation, while it was ineffective once the process of differentiation was
      underway. These data suggest that the insulin signal is effective during an early
      window of time before cell confluence, while normal c-Ras levels are required for
      its transmission.

PMID- 9149121
TI  - Inhibition of 12-O-tetradecanoylphorbol-13-acetate induced Epstein-Barr virus
      early antigen activation by natural colorants.
AB  - Natural colorants such as anthocyanins, betalains, carotenoids, curcuminoids and
      chlorophylls have been widely used in the food processing industry and in
      beverages. Most of these colorants constitute part of human dietary components
      and are considered to be harmless and non-toxic. As a part of the study of
      natural products to identify non-toxic cancer chemopreventive agents, we have
      investigated several natural colorant extracts from vegetables and fruits of
      daily human consumption for their cancer chemopreventive action using the short
      term in vitro assay which involves inhibition of Epstein-Barr virus early antigen
      activation (EBV-EA) induced by phorbol esters. Our study has identified several
      plant extracts that show profound activity in the EBA assay.

PMID- 9149122
TI  - Inhibitory effects on Epstein-Barr virus activation of anthraquinones:
      correlation with redox potentials.
AB  - The redox potentials have been determined for nine anthraquinones in phosphate
      buffer at pH 7.2 by means of cyclic voltammetry. A definite correlation has been
      found between the redox potentials and the inhibitory effects of the
      anthraquinones on the EBV-EA activation. It has further been shown that the
      correlation can be made better by introducing an electronic property, i.e. the
      atomic charge at O12 as an additional parameter.

PMID- 9149123
TI  - Apoptosis and metastasis: increased apoptosis resistance of metastatic cancer
      cells is associated with the profound deficiency of apoptosis execution
      mechanisms.
AB  - Programmed cell death, particularly adhesion-dependent regulation of cell
      survival and apoptosis, is recognized as one of the main homeostatic mechanisms
      designed to control cell positioning, eliminate misplaced cells and block
      metastatic dissemination. Recently we reported that highly metastatic cancer
      cells exhibit a higher resistance to the programmed cell death compared to their
      poorly metastatic counterparts (Cancer Lett., 101, 43-51, 1996). However, the
      molecular and genetic basis for the association of aggressive metastatic
      phenotype with resistance toward apoptosis remains to be elucidated. Here we
      extended our investigation on apoptosis and metastasis using a panel of nine
      murine and human cancer cell lines with different metastatic potential. We
      examined the relationship of the metastatic ability and the sensitivity to
      apoptosis as well as determined the status of two major apoptosis execution
      mechanisms (induction of nuclear Ca2+-dependent endonucleases and activation of
      ICE-like proteases) in cancer cells with distinct metastatic potential and
      different sensitivity to apoptosis. We found that high metastatic potential is
      strictly associated with the increased resistance to apoptosis, diminished level
      of nuclear Ca2+-dependent endonucleases, and significantly reduced activity of
      CPP32/Yama death protease. We concluded that high resistance to apoptosis of
      metastatic cancer cells is associated with and may depend upon the profound
      deficiency of major apoptosis execution mechanisms.

PMID- 9149125
TI  - p16 tumor suppressor gene mutations in Chinese esophageal carcinomas in Hong
      Kong.
AB  - The frequency and nature of genetic alterations in the p16 tumor suppressor gene
      in 25 esophageal squamous cell carcinoma specimens from Chinese patients were
      investigated by PCR-SSCP and DNA sequencing techniques. No gross deletions
      occurred in either exon 1 and 2 of the gene by PCR amplification. However,
      genetic changes were observed in three cases. These included a point mutation in
      codon 12 of exon 1 with a resulting Ala --> Thr amino acid substitution, a point
      mutation at base 91 in the non-coding region of exon 1, and a 1 base pair
      insertion in codon 116 of exon 2. The low mutation frequency of 12% is consistent
      with that of three previous studies involving Japanese and Caucasian patients (8,
      16 and 21% frequency: Esteve et al., 1996, Igaki et al., 1995 and Zhou et al.,
      1994). p16 gene mutations do not appear to play a major role in esophageal
      carcinogenesis.

PMID- 9149124
TI  - Optimization of chemotherapy administration for clinical 41.8 degrees C whole
      body hyperthermia.
AB  - Preclinical data is consistent with the concept that the timing of chemotherapy
      during radiant heat-whole body hyperthermia (WBH) should affect therapeutic
      index. In order to test this hypothesis, a controlled clinical investigation was
      initiated. Patients received carboplatin (CBDCA) on an early or late schedule
      with respect to achieving target temperature (i.e. 41.8 degrees C) in alternating
      treatment cycles. The first cycle was randomized between patients regarding the
      early or late schedule for two planned sets per patient (i.e. four cycles).
      Ifosfamide, etoposide and granulocyte colony stimulating factor were delivered
      during all cycles with a standardized schedule. A total of 53 cycles involving 17
      patients were analyzed. Detailed toxicity evaluation (i.e. delay in therapy
      secondary to thrombocytopenia, need for platelet transfusions, and days of
      hospitalization) taken collectively demonstrated a statistically and clinically
      significant advantage to delivering CBDCA 10 min after target temperature, during
      the plateau phase of WBH.

PMID- 9149126
TI  - Expression of E-cadherin and alpha- and beta-catenin mRNAs in ovarian cancers.
AB  - To know the biological role of the adherens junction, mainly consisting of E
      cadherin and alpha- and beta-catenins, associated with invasion and metastasis of
      ovarian cancers, we studied the expressions of E-cadherin and alpha- and beta
      catenin mRNAs in the cancers in comparison with those in normal counterparts. The
      integral expression of E-cadherin and alpha- and, beta-catenin mRNAs was
      suppressed in the metastatic lesions of advanced ovarian cancers, while it was
      not in the primary tumors. Therefore, the suppressed expression of main adhesion
      molecules in the adherens junction might contribute to adherens junctional
      dysfunction, which might lead to the acquirement of invasiveness and metastatic
      potential by advanced ovarian cancers as one of the rate-limiting steps.

PMID- 9149127
TI  - Promoting activity of 3-tert-butyl-4-hydroxyanisole (BHA) in BALB/3T3 cell
      transformation.
AB  - 3-Tert-butyl-4-hydroxyanisole (BHA), a synthetic antioxidant, is an initiator in
      the transformation of BALB/3T3 mouse embryo cells, when cells are treated first
      with the chemical and then with a tumor promoter, 12-O-tetradecanoylphorbol-13
      acetate. In the present study, BHA was examined for its promoting activity in
      BALB/3T3 cell transformation. BHA in a range of 5-20 microg/ml enhanced
      transformation induced by a subthreshold dose of 3-methylcholanthrene (MCA, 0.1
      microg/ml) in a dose-dependent manner. Statistically significant increases were
      noted in the proportion of dishes with transformed foci in the cultures treated
      with 10 and 20 microg/ml BHA following MCA as compared to the cultures treated
      with MCA alone. When BHA was applied to the cultures both on initiating and
      promoting stages in the absence of another initiator or promoter, however, BHA
      did not increase the transformation frequency, suggesting that the transforming
      activities of BHA are too weak and require combination with a potent initiator or
      promoter to attain complete transformation in this assay system. BHA did not
      increase postconfluent cell density nor induce DNA synthesis in density-arrested
      cells, suggesting that cell proliferation is excluded from the causal events of
      transformation enhancement by BHA in BALB/3T3 cells.

PMID- 9149128
TI  - The human KB multidrug-resistant cell line KB-C1 is hypersensitive to inhibitors
      of glycosylation.
AB  - We have previously shown that the hypersensitivity of KB MDR cells to 2-deoxy-D
      glucose is associated with diminished plasma membrane GLUT-1 levels compared with
      parental, non-MDR cells. Here we report that MDR cells are hypersensitive to the
      N-linked glycosylation inhibitor tunicamycin, which induces partial inhibition of
      GLUT-1 glycosylation and diminishes GLUT-1-mediated transport. The effect of
      tunicamycin, which also enhances the hypersensitivity of MDR cells to 2-deoxy-D
      glucose, could not be attributed to alterations in P-glycoprotein activity. The
      use of agents that act synergistically to diminish the level and activity of GLUT
      1 in MDR cells may be of clinical potential.

PMID- 9149129
TI  - Sulindac sulfide inhibits the proliferation of colon cancer cells: diminished
      expression of the proliferation markers PCNA and Ki-67.
AB  - We evaluated the effect of sulindac sulfide (SS), which reduces cell number and
      induces apoptosis in cultured colon cancer cells (CCCs), on expression of the
      proliferation markers PCNA and Ki-67 in HT-29 and HCT-15 CCCs; only the former
      express cyclooxygenases. DNA content and PCNA/Ki-67 expression were analyzed by
      bivariate flow cytometry. SS inhibited cell proliferation, determined by the
      reduced expression of PCNA and Ki-67, roughly by half at 72 h, and induced
      apoptosis (accounting for about two-thirds and one-third of the reduction in cell
      number, respectively). A similar effect of SS occurred in HT-29 and HCT-15 CCCs,
      and also in non-colonic cells, indicating that this rather general effect of SS
      on cultured cells is not dependent on inhibition of prostaglandin synthesis.

PMID- 9149130
TI  - Marked elevation of hypusine formation activity on eukaryotic initiation factor
      5A in v-HA-RAS transformed mouse NIH3T3 cells.
AB  - Hypusine formation on the eukaryotic initiation factor 5A (eIF-5A) precursor is
      ubiquitously present in eukaryotic cells and archebacteria. In this reaction,
      deoxyhypusine synthase catalyzes the conversion of one unique lysine residue on
      eIF-5A to deoxyhypusine using spermidine as the substrate. Hydroxylation of the
      deoxyhypusine residue completes hypusine formation on eIF-5A. Hypusine formation
      activity can be measured by an in vitro labeling technique in polyamine-depleted
      cells. In addition, an in vitro cross-labeling assay can be employed to measure
      simultaneously the relative deoxyhypusine synthase activity and protein substrate
      amount. Using these approaches, together with Western blot analysis, we showed
      that hypusine formation activity is serum-responsive and significantly elevated
      in Ras oncogene transfected NIH3T3 cells as compared to NIH3T3 cells. The large
      difference, >30-fold, in hypusine formation activity between these two cells is
      mainly due to difference in the amount of newly synthesized eIF-5A precursor
      rather than deoxyhypusine synthase. The deoxyhypusine synthase activity is about
      three-fold higher in Ras-3T3 cells than in 3T3 cells, and remains constant
      throughout serum stimulation in both cells. Despite the significant difference in
      eIF-5A protein amounts, the eIF-5A mRNA levels in 3T3 cells and in Ras-3T3 cells
      are almost identical. Furthermore, unlike serum-dependent increase in eIF-5A
      precursor protein, the eIF-5A mRNA in both cells is constitutively expressed
      after serum stimulation, suggesting that eIF-5A gene is regulated at
      posttranscriptional/translational level during serum stimulation and cell
      transformation.

PMID- 9149131
TI  - Extensive DNA damage induced by monochloramine in gastric cells.
AB  - Colonization of Helicobacter pylori (Hp) to gastric mucosa plays an important
      role for the pathogenesis of gastric mucosal lesions. We previously reported the
      importance of monochloramine (NH2Cl), which was derived from the interaction
      between Hp-urease and infiltrated leukocytes, in the course of Hp-associated
      gastric mucosal injury. While the long-term infection of Hp in the gastric mucosa
      is known to be one of the virulent factors which closely link to the gastric
      carcinogenesis, the details of its pathogenetic mechanisms remain speculative.
      The present study is designed to examine whether a NH2Cl could damage the DNA of
      gastric cells. Rabbit gastric mucosal cells (RGMC) or KATO III cells were
      cultured and suspended. Cell suspensions were exposed to HOCl, NH3 or NH2Cl for
      15 min to give a final concentration of 0.1 mM. The magnitude of a double strand
      break of DNA was quantified by measuring the remnant double strand stained by
      ethidium bromide (EB), and the fluorescence intensity of EB was analyzed by
      spectrophotometer. Separately, cell nuclei were stained by fluorescent dye
      (Hoechst No. 33258) in order to evaluate the levels of chromatin condensation
      evoked by DNA fragmentation. The number of cells with chromatin condensation was
      counted. During the entire experimental period, more than 85% of cells were
      persistently viable in all groups. NH2Cl significantly induced the DNA double
      strand break as well as chromatin condensation in RGMC and KATO III cells (P <
      0.05). However, NH3 or HOCl did not induce the DNA double strand break as well as
      chromatin condensation in both cells. NH2Cl, but not its precursors (NH3 or
      HOCl), enhanced the levels of DNA injury, suggesting the possible involvement in
      the carcinogenesis of Hp-associated gastric mucosa.

PMID- 9149132
TI  - Lack of involvement of p53 gene mutations in N-methyl-N-nitrosourea-induced
      bladder tumor progression in N-butyl-N-(4-hydroxybutyl)nitrosamine-treated rats
      and no suppression by indomethacin.
AB  - The relevance of p53 mutations to rat bladder cancer progression induced by a
      single injection of N-methyl-N-nitrosourea (MNU) and the chemopreventive effects
      of indomethacin (IM) were investigated in male F344 rats, initially given N-butyl
      N-(4-hydroxybutyl)nitrosamine (BBN) at a dose of 500 ppm in the drinking water
      for 10 weeks. The animals were subsequently treated with a single intraperitoneal
      injection of MNU at a dose of 50 mg/kg b.w. at week 20. A subgroup was then given
      IM dissolved in the drinking water at a concentration of 20 ppm for 20 weeks. The
      experiment was terminated at week 40 when transitional cell carcinomas (TCC) were
      observed in all animals given BBN, regardless of the administration of MNU and/or
      IM (incidences ranged from 80 to 100%). The extent of invasion was significantly
      greater with the additional MNU treatment but no inhibitory effects of IM were
      noted. A low frequency of p53 mutations was detected without relation to the
      extent of tumor invasion. Thus, only two mutations were found, one in a Ta and
      the other in a T1 carcinoma. The present study thus demonstrated that p53
      mutations are not involved in MNU-induced progression in rat urinary bladder
      cancers, suggesting that they are not critical for malignancy.

PMID- 9149133
TI  - Expression and identification of aberrant c-kit transcripts in human cancer
      cells.
AB  - We have previously cloned and sequenced a novel 3.5 kb c-kit mRNA expressed in a
      colon carcinoma cell line Colo201. Here we examined the expression of this
      truncated form of c-kit in 14 gastrointestinal cancer cells and 16 hematopoieic
      cancer cells by RT-PCR. Expression of the aberrant c-kit transcript was observed
      in various cancer cell lines. Furthermore, a new transcript which is 78 bp
      shorter than the transcript previously described was identified and
      characterized. These results indicate that two kinds of aberrant c-kit transcript
      produced by alternative promoter in intron 15 are expressed in human cancer
      cells.

PMID- 9149135
TI  - Study of plasmid replication in Escherichia coli with a combination of 2D gel
      electrophoresis and electron microscopy.
AB  - We studied theta-mode DNA replication in p15A-based Escherichia coli plasmids by
      analyzing their replication intermediates using a combination of neutral agarose
      2D gel electrophoresis and electron microscopy. Our analysis: (1) confirms the
      original assignment of various features of the 2D gel pattern; (2) shows that
      while one replication fork progresses around the plasmid DNA, the other is
      immobile, as if the replication were unidirectional; and (3) reveals that
      termination often occurs at a location away from the replication origin,
      suggesting that the replication of our plasmids is, in fact, bidirectional, the
      two forks being active at different times.

PMID- 9149136
TI  - A statistical model for locating regulatory regions in genomic DNA.
AB  - In addition to genes, chromosomal DNA contains sequences that serve as signals
      for turning on and off gene expression. These signals are thought to be
      distributed as clusters in the regulatory regions of genes. We develop a Bayesian
      model that views locating regulatory regions in genomic DNA as a change-point
      problem, with the beginning of regulatory and non-regulatory regions
      corresponding to the change points. The model is based on a hidden Markov chain.
      The data consist of nucleotide positions of protein-binding elements in a genomic
      DNA sequence. These positions are identified using a reference catalogue
      containing elements that interact with transcription factors implicated in
      controlling the expression of protein-encoding genes. Among the protein-binding
      elements in a genomic DNA sequence, the statistical model automatically selects
      those that tend to predict regulatory regions. We test the model using viral
      sequences that include known regulatory regions and provide the results obtained
      for human genomic DNA corresponding to the beta globin locus on chromosome 11.

PMID- 9149137
TI  - Six molecules of SV40 large T antigen assemble in a propeller-shaped particle
      around a channel.
AB  - The large T antigen of simian virus 40 (SV40) is a multifunctional regulatory
      protein, responsible for both the control of viral infection and the required
      alterations of cellular processes. T antigen is the only viral protein required
      for viral DNA replication. It binds specifically to the viral origin and as a
      helicase unwinds the SV40 DNA bidirectionally. The functional complex is a double
      hexameric oligomer. In the absence of DNA, but in the presence of ATP or a non
      hydrolyzable analog, T antigen assembles into hexamers, which are active as a
      helicase when a partially single-stranded (3') entry site exists on the
      substrate. We have used negative staining electron microscopy, single particle
      image processing and three-dimensional reconstruction with a new algebraic
      reconstruction techniques (ART) algorithm to study the structure of these
      hexameric particles in the presence of different nucleotide cofactors (ATP, ADP,
      and the non-hydrolyzable analogs ATPgammaS and AMP-PNP). In every case a strong 6
      fold structure was found, with the six density maxima arranged in a ring-like
      particle around a channel, and a well-defined vorticity. Because these structural
      features have recently been found in other prokaryotic helicases, they seem to be
      strongly related to the activity of the protein, which suggests a general
      functional model conserved through evolution.

PMID- 9149138
TI  - Structure and function of the dihydropteroate synthase from Staphylococcus
      aureus.
AB  - The gene encoding the dihydropteroate synthase of staphylococcus aureus has been
      cloned, sequenced and expressed in Escherichia coli. The protein has been
      purified for biochemical characterization and X-ray crystallographic studies. The
      enzyme is a dimer in solution, has a steady state kinetic mechanism that suggests
      random binding of the two substrates and half-site reactivity. The crystal
      structure of apo-enzyme and a binary complex with the substrate analogue
      hydroxymethylpterin pyrophosphate were determined at 2.2 A and 2.4 A resolution,
      respectively. The enzyme belongs to the group of "TIM-barrel" proteins and
      crystallizes as a non-crystallographic dimer. Only one molecule of the substrate
      analogue bound per dimer in the crystal. Sequencing of nine sulfonamide-resistant
      clinical isolates has shown that as many as 14 residues could be involved in
      resistance development. The residues are distributed over the surface of the
      protein, which defies a simple interpretation of their roles in resistance.
      Nevertheless, the three-dimensional structure of the substrate analogue binary
      complex could give important insight into the molecular mechanism of this enzyme.

PMID- 9149139
TI  - Protein secondary structure prediction using local alignments.
AB  - The accuracy of secondary structure prediction methods has been improved
      significantly by the use of aligned protein sequences. The PHD method and the
      NNSSP method reach 71 to 72% of sustained overall three-state accuracy when
      multiple sequence alignments are with neural networks and nearest-neighbor
      algorithms, respectively. We introduce a variant of the nearest-neighbor approach
      that can achieve similar accuracy using a single sequence as the query input. We
      compute the 50 best non-intersecting local alignments of the query sequence with
      each sequence from a set of proteins with known 3D structures. Each position of
      the query sequence is aligned with the database amino acids in alpha-helical,
      beta-strand or coil states. The prediction type of secondary structure is
      selected as the type of aligned position with the maximal total score. On the
      dataset of 124 non-membrane non-homologous proteins, used earlier as a benchmark
      for secondary structure predictions, our method reaches an overall three-state
      accuracy of 71.2%. The performance accuracy is verified by an additional test on
      461 non-homologous proteins giving an accuracy of 71.0%. The main strength of the
      method is the high level of prediction accuracy for proteins without any known
      homolog. Using multiple sequence alignments as input the method has a prediction
      accuracy of 73.5%. Prediction of secondary structure by the SSPAL method is
      available via Baylor College of Medicine World Wide Web server.

PMID- 9149140
TI  - Effects of neutral salts on RNA chain elongation and pausing by Escherichia coli
      RNA polymerase.
AB  - We examined the effects of neutral salts and the non-ionic solute 2-methyl,-2,4
      pentanediol (MPD) on transcript elongation by Escherichia coli RNA polymerase and
      on pausing induced by the multipartite his leader pause signal. All solutes
      tested slowed the overall rate of elongation, with anions showing the dominant
      effects in the order: (most inhibitory) HPO4(2-) > OAc- > SO4(2-) > ClO4- > I-
      approximately NO3- > Br approximately Cl- approximately MPD (least inhibitory).
      Although the protein structure-stabilizing anions HPO4(2-), OAc-, and SO4(2-)
      also increased the pause half-life at the his leader pause site, the remaining
      solutes accelerated escape from pause site in the order: (greatest acceleration)
      NO3- > ClO4- > I- > Br- > Cl- > MPD (least acceleration). Cl(-)-induced
      acceleration of escape from the pause site also occurred on mutant templates
      altered for the 3'-proximal region, RNA 3' end, or downstream DNA. The effect was
      eliminated, however, by base substitutions that destabilize the pause RNA hairpin
      or that extend it toward the 3' end. This "perfect hairpin" itself reduced the
      pause half-life by a factor of 3. We suggest that the pause RNA hairpin
      stabilizes a paused conformation of the transcription complex through an
      interaction with an easily disordered region of RNA polymerase. Extending the
      stem of the pause hairpin may disrupt the interaction by altering the position of
      the hairpin in the transcription complex. Anions may either compete for the
      interaction directly or disorder the site of hairpin interaction by chaotropic
      effects. We suggest that the negative effect of structure-stabilizing anions like
      OAc- and SO4(2-) may reflect passage of RNA polymerase through significantly
      different conformations during rapid elongation, some of which may expose
      hydrophobic surface.

PMID- 9149141
TI  - Multiple interactions stabilize a single paused transcription intermediate in
      which hairpin to 3' end spacing distinguishes pause and termination pathways.
AB  - Transcription is delayed in the leader regions of the Escherichia coli trp and
      his operons by multipartite pause signals that consist of four components: a
      nascent RNA structure (the pause hairpin), the 10 or 11 nt 3'-proximal region
      between the pause hairpin and the RNA 3' end, the bases in the active site, and
      approximately 14 bp of duplex DNA downstream from the pause site. Results
      described in the accompanying paper suggest that the his pause hairpin slows
      nucleotide addition via interaction with an easily disordered surface on RNA
      polymerase. Here we report that the four pause signal components slow nucleotide
      addition in a single kinetic intermediate. Formation of the paused transcription
      complex, in contrast, involves synergistic effects of RNA and DNA sequences that
      select the wild-type pause site from among several adjacent possibilities.
      Extending the pause hairpin with one G x C base-pair reduces pausing, apparently
      by interfering with pause hairpin interaction; adding a second C x G base-pair
      that reduces the 3'-proximal RNA to 9 nt or less (within the 7 to 9 nt
      characteristic of rho-independent terminators) induces transcript release. We
      propose that escape from the pause is governed by a rate-limiting isomerization
      that may require substrate NTP binding to re-establish the active site geometry,
      whereas transcript release and termination ensue when the hairpin interaction is
      weakened and isomerization to an active conformation is blocked.

PMID- 9149142
TI  - The creation of diversity in the human immunoglobulin V(lambda) repertoire.
AB  - Sequence diversity in the human antibody repertoire is generated in two steps: by
      the combinatorial assembly of V gene segments and by somatic hypermutation. Here,
      we have characterised these processes for the lambda (lambda) light chain using a
      library of 7600 lambda cDNA clones from peripheral blood lymphocytes. By
      hybridisation and sequencing we found that most lambda chains are derived from
      the cluster of V(lambda) segments closest to the J(lambda)-C(lambda) pairs and
      that there is considerable variation in the use of individual V(lambda) segments
      (ranging from 0.02% to 27%): three of the 30 functional V(lambda) segments encode
      half the expressed V(lambda) repertoire. As a result of these biases, sequence
      diversity in the primary repertoire is focused at the centre of the antigen
      binding site. By contrast, somatic hypermutation spreads diversity to the
      periphery. Comparison with the human kappa (kappa) light chain indicates that
      both kappa and lambda use the same strategy for searching sequence space and have
      almost identical patterns of diversity in the mature antibody repertoire.

PMID- 9149143
TI  - Prediction of complete gene structures in human genomic DNA.
AB  - We introduce a general probabilistic model of the gene structure of human genomic
      sequences which incorporates descriptions of the basic transcriptional,
      translational and splicing signals, as well as length distributions and
      compositional features of exons, introns and intergenic regions. Distinct sets of
      model parameters are derived to account for the many substantial differences in
      gene density and structure observed in distinct C + G compositional regions of
      the human genome. In addition, new models of the donor and acceptor splice
      signals are described which capture potentially important dependencies between
      signal positions. The model is applied to the problem of gene identification in a
      computer program, GENSCAN, which identifies complete exon/intron structures of
      genes in genomic DNA. Novel features of the program include the capacity to
      predict multiple genes in a sequence, to deal with partial as well as complete
      genes, and to predict consistent sets of genes occurring on either or both DNA
      strands. GENSCAN is shown to have substantially higher accuracy than existing
      methods when tested on standardized sets of human and vertebrate genes, with 75
      to 80% of exons identified exactly. The program is also capable of indicating
      fairly accurately the reliability of each predicted exon. Consistently high
      levels of accuracy are observed for sequences of differing C + G content and for
      distinct groups of vertebrates.

PMID- 9149144
TI  - Maturation of mammalian 20 S proteasome: purification and characterization of 13
      S and 16 S proteasome precursor complexes.
AB  - The maturation of the eukaryotic 20 S proteasome complex occurs via 13 S and 16 S
      precursor complexes in a multistep assembly pathway. These precursor complexes
      contain alpha-subunits as well as unprocessed beta-subunit proproteins. We have
      purified and characterized the different proteasome assembly intermediates and
      analysed their ability to support beta-subunit proprotein processing in vitro.
      Our data show that 13 S and 16 S proteasome precursor complexes differ not only
      in size but also in their protein content and behaviour during hydrophobic
      chromatography. By establishing conditions which allowed us to analyse beta
      prosubunit maturation in vitro we demonstrate that the processing of the
      homologous proproteins of the beta-subunits LMP2 and delta essentially takes
      place in 16 S precursor complexes. No proprotein processing activity was observed
      in 13 S precursor complexes. Furthermore, proprotein processing in vitro can be
      inhibited with a proteasome specific inhibitor, but with different efficiency for
      LMP2 and delta. A peptide, which represents the sequence of the proprotein
      processing site HGTT, exhibited no inhibitory effect on the processing of either
      subunit. These data provide further evidence that proprotein processing occurs
      via an autocatalytic mechanism. Our experiments also demonstrate that the
      chaperone protein hsc73 is associated with 16 S but not with 13 S precursor
      complexes. In support of the specificity of this interaction incubation with ATP
      leads to the dissociation of hsc73 from 16 S complexes and to the formation of
      high molecular weight aggregates. Prosubunit processing in isolated 16 S
      complexes does not, however, result in the formation of proteolytically active 20
      S proteasomes which may be due to the fact that not all beta-subunits can be
      efficiently processed in vitro. In contrast to previous assumptions subunit
      processing and formation of proteolytic activity do not coincide and final 20 S
      complex assembly seems to represent in part a separate event which requires
      additional factors or proteins which are not present or active in the purified 16
      S precursor complexes.

PMID- 9149145
TI  - Stabilization of a recombinant Fv fragment by base-loop interconnection and V(H)
      V(L) permutation.
AB  - We have developed a novel method to stabilize a recombinant antibody Fv fragment.
      The V(H) and V(L) domains of this Fv fragment, called pFv (permutated Fv), are
      covalently interconnected to each other at the two "base-loops" that normally
      connect V(H) beta strand 3 to 3b and V(L) beta strand 3 to 3b. To produce the
      base-loop stabilized Fv fragment, we connected the N-terminal half of the V(L)
      domain (V(L) 1-40) of murine antibody anti-Tac to the C-terminal half of V(H)
      (V(H) 42-115). We also fused the C terminus of V(H) by a (Gly4Ser)3 linker to the
      N-terminal half of V(H) (V(H) 1-40, thereby generating a permutated V(H) domain).
      Finally we connected the base loop of V(H) (N-terminal half) to the C-terminal
      half of V(L) (V(H) 42-115). The anti-Tac pFv fragment was fused to a truncated
      form of Pseudomonas exotoxin to generate a pFv-immunotoxin. Fvs with the correct
      structure were produced by refolding of recombinant inclusion body protein using
      a renaturation protocol that was originally developed for Fab and scFv fragments.
      Due to the artificially connected and permutated primary sequence, the folding
      pathway for the pFv structure may possibly be different from the conventional
      folding of antibody domains. Analysis of antigen binding of anti-Tac pFv, and of
      the specific cytotoxicity of pFv-immunotoxin towards antigen expressing cancer
      cells demonstrated that the anti-Tac pFv retained most of its affinity and full
      specificity when compared to anti-Tac scFv. Also anti-Tac pFv was relatively
      stable, retaining 25% of its binding activity after a 24 hour incubation in human
      serum at 37 degrees C. This indicates that connection of base loops can be a
      useful alternative to linker or disulfide stabilization of Fv fragments.

PMID- 9149146
TI  - Kinetics of DNA hydration.
AB  - The hydration of the d(CGCGAATTCGCG) B-DNA duplex in solution was studied by
      nuclear magnetic relaxation dispersion (NMRD) of the water nuclei 1H, 2H, and
      17O, and by nuclear Overhauser effects (NOEs) in high-resolution two-dimensional
      1H NMR spectra. By comparing results from the free duplex with those from its
      complex with netropsin, water molecules in the "spine of hydration" in the AATT
      region of the minor groove could be distinguished from hydration water elsewhere
      in the duplex. The 2H and 17O relaxation dispersions yield a model-independent
      residence time of 0.9(+/-0.1) ns at 4 degrees C for five highly ordered water
      molecules in the spine. When corrected for frequency offset effects, the NOE data
      yield the same residence time as the NMRD data, giving credence to both methods.
      At 27 degrees C, the residence time is estimated to 0.2 ns, a factor of 40
      shorter than the tumbling time of the duplex. The NMRD data show that all water
      molecules associated with the duplex, except the five molecules in the spine,
      have residence times significantly shorter than 1 ns at 4 degrees C. There is
      thus no long-lived hydration structure associated with the phosphate backbone. In
      contrast to 2H and 17O, the 1H relaxation dispersion is dominated by labile DNA
      protons and therefore provides little information about DNA hydration.

PMID- 9149147
TI  - Structure of TcpG, the DsbA protein folding catalyst from Vibrio cholerae.
AB  - The efficient and correct folding of bacterial disulfide bonded proteins in vivo
      is dependent upon a class of periplasmic oxidoreductase proteins called DsbA,
      after the Escherichia coli enzyme. In the pathogenic bacterium Vibrio cholerae,
      the DsbA homolog (TcpG) is responsible for the folding, maturation and secretion
      of virulence factors. Mutants in which the tcpg gene has been inactivated are
      avirulent; they no longer produce functional colonisation pili and they no longer
      secrete cholera toxin. TcpG is thus a suitable target for inhibitors that could
      counteract the virulence of this organism, thereby preventing the symptoms of
      cholera. The crystal structure of oxidized TcpG (refined at a resolution of 2.1
      A) serves as a starting point for the rational design of such inhibitors. As
      expected, TcpG has the same fold as E. coli DsbA, with which it shares
      approximately 40% sequence identity. In addition, the characteristic surface
      features of DsbA are present in TcpG, supporting the notion that these features
      play a functional role. While the overall architecture of TcpG and DsbA is
      similar and the surface features are retained in TcpG, there are significant
      differences. For example, the kinked active site helix results from a three
      residue loop in DsbA, but is caused by a proline in TcpG (making TcpG more
      similar to thioredoxin in this respect). Furthermore, the proposed peptide
      binding groove of TcpG is substantially shortened compared with that of DsbA due
      to a six-residue deletion. Also, the hydrophobic pocket of TcpG is more shallow
      and the acidic patch is much less extensive than that of E. coli DsbA. The
      identification of the structural and surface features that are retained or are
      divergent in TcpG provides a useful assessment of their functional importance in
      these protein folding catalysts and is an important prerequisite for the design
      of TcpG inhibitors.

PMID- 9149148
TI  - The three-dimensional structure of flavodoxin reductase from Escherichia coli at
      1.7 A resolution.
AB  - Flavodoxin reductase from Escherichia coli is an FAD-containing oxidoreductase
      that transports electrons between flavodoxin or ferredoxin and NADPH. Together
      with flavodoxin, the enzyme is involved in the reductive activation of three E.
      coli enzymes: cobalamin-dependent methionine synthase, pyruvate formate lyase and
      anaerobic ribonucleotide reductase. An additional function for the oxidoreductase
      appears to be to protect the bacteria against oxygen radicals. The three
      dimensional structure of flavodoxin reductase has been solved by multiple
      isomorphous replacement, and has been refined at 1.7 A to an R-value of 18.4% and
      Rfree 24.8%. The monomeric molecule contains one beta-sandwich FAD domain and an
      alpha/beta NADP domain. The overall structure is similar to other reductases of
      the NADP-ferredoxin reductase family in spite of the low sequence similarities
      within the family. Flavodoxin reductase lacks the loop which is involved in the
      binding of the adenosine moiety of FAD in other FAD binding enzymes of the
      superfamily but is missing in the FMN binding phthalate dioxygenase reductase.
      Instead of this loop, the adenine interacts with an extra tryptophan at the C
      terminus. The FAD in flavodoxin reductase has an unusual bent conformation with a
      hydrogen bond between the adenine and the isoalloxazine. This is probably the
      cause of the unusual spectrum of the enzyme. There is a pronounced cleft close to
      the isoalloxazine that appears to be well suited for binding of
      flavodoxin/ferredoxin. Two extra short strands of the NADP-binding domain
      probably act as an anchor point for the binding of flavodoxin.

PMID- 9149149
TI  - Characterization of long-range structure in the denatured state of staphylococcal
      nuclease. I. Paramagnetic relaxation enhancement by nitroxide spin labels.
AB  - Structural analysis of delta131delta, a fragment model of the denatured state of
      staphylococcal nuclease, has been extended by obtaining long-range distance
      restraints between protein chain segments based on paramagnetic relaxation
      enhancement methods. PROXYL spin labels were attached at unique cysteine residues
      introduced at 14 different sites along the polypeptide chain, and the resulting
      enhancements of amide proton relaxation were measured by NMR spectroscopy. To
      minimize perturbation of denatured state structure, these labeling sites were
      chosen on the basis of a high solvent exposure in the native state and a small
      change in stability and m-value upon mutation of the wild-type residue to
      cysteine or alanine. EPR spectroscopy confirmed that in all cases the PROXYL
      label of the modified protein was solvent-exposed and undergoing free isotropic
      rotation. By quantifying at 500 MHz and 600 MHz the enhancement of both T1 and T2
      relaxation for amide protons resolved in a 1H-15N correlation spectrum, the
      apparent correlation time for the free electron-proton vectors for six PROXYL
      labeled proteins could be estimated. With these data plus the enhancements in
      transverse relaxation rate (R2) for the other eight proteins, the time-averaged,
      r(-6) weighted distance between the free electron on the unique nitroxide and 30
      to 60 amide protons in each protein could be approximated. Inspection of the
      pattern of R2 enhancements reveals a significant amount of long-range structure
      in this denatured state, a clear indication that it is not a random coil.

PMID- 9149150
TI  - Characterization of long-range structure in the denatured state of staphylococcal
      nuclease. II. Distance restraints from paramagnetic relaxation and calculation of
      an ensemble of structures.
AB  - Structural analysis of delta131delta, a fragment model of the denatured state of
      staphylococcal nuclease, has been extended by obtaining long-range distance
      restraints between chain segments by paramagnetic relaxation enhancement.
      Fourteen unique PROXYL spin labels were introduced at sites that are solvent
      exposed in the native state, and the resulting enhancements of T2 for the amide
      protons were measured by NMR spectroscopy. When these data were combined with
      either measured or estimated correlation times tau(c), the r(-6)-weighted, time
      and ensemble-averaged distance between the spin label and 30 to 60 amide protons
      could be calculated for each spin-labeled protein. On the basis of approximately
      700 such loose distance restraints, ensembles of compatible structures were
      generated by a combined distance geometry/molecular dynamics approach. Because of
      the large uncertainty in the physical basis of these distance restraints, a
      number of calculations were carried out to establish the sensitivity of the
      calculated structures to systematic errors in these restraints. Overall, the
      structural features reflected in the paramagnetic relaxation data were robust;
      large variations in tau(c), in the bounds window of allowed distances, or in the
      number of restraint distances used had small effects on the general features
      common to all calculated structures. The global topology of this denatured form
      of staphylococcal nuclease, as described by an ensemble of conformations
      consistent with the data, is strikingly similar to that of the native state, the
      major difference being the segregation of two hydrophobic segments that form a
      beta hairpin in the native state. These findings suggest that the topology of a
      protein's fold is established in the denatured state in the absence of
      cooperative interactions involving tight packing or stable hydrogen bonding.
      Hydrophobic interactions alone may encode global topology.

PMID- 9149151
TI  - Following co-operative formation of secondary and tertiary structure in a single
      protein module.
AB  - We have prepared a family of peptide fragments of the 64 amino acid protein
      chymotrypsin inhibitor (CI2), corresponding to progressive elongation from the N
      terminus, in order to elucidate the basis of conformational preferences in single
      domain proteins and to obtain insights into their conformational pathway.
      Structural analysis of the fragment comprising the first 50 residues, CI2(1-50),
      indicates that it is mainly disordered, with patches of hydrophobic residues
      exposed to the solvent. Structural characterisation of the fragment CI2(1-63)
      which lacks only the C-terminal glycine, Gly64, shows native-like structure in
      all regions of the fragment. The study provides insights into the contribution of
      specific residues to the stability and co-operativity of the intact protein. We
      define a phiNMR value, derived from chemical shift analysis, which describes the
      build-up of structure at the level of individual residues (protons). All the
      macroscopic probes used to study the growth of structure in CI2 on elongation of
      the chain (circular dichroism, fluorescence and gel filtration) are in agreement
      with the residue-by-residue description by NMR. It is seen that secondary and
      tertiary structure build up in parallel in the fragments and show similar
      structures to those developed in the transition state for folding of the intact
      protein.

PMID- 9149152
TI  - Thermodynamics of denaturation of mutants of barnase with disulfide crosslinks.
AB  - We have measured the effects of disulfide crosslinks on the thermodynamics of
      denaturation of three mutants of barnase that contain cystine and the
      corresponding single and double cysteine mutants. At first sight, the data are
      consistent with the hypothesis that disulfide crosslinks stabilise proteins
      through entropic destabilisation of the denatured state, but the decreases in the
      entropy of denaturation are larger than predicted and are accompanied by
      decreases in the enthalpy of denaturation. These effects are not a unique feature
      of the disulfide crosslink and are observed in a range of non-crosslinked mutants
      of barnase as part of a general enthalpy-entropy compensation phenomenon.
      Similarly, effects on the heat capacity change for denaturation (delta C(p)d),
      determined from the slope of the enthalpy of denaturation versus temperature, are
      not confined to mutants with disulfide crosslinks. The value of delta C(p)d is
      lower in four stabilised mutants than in wild-type barnase, irrespective of the
      presence of a disulfide crosslink, while the delta C(p)d remains unchanged in a
      destabilised mutant containing a disulfide. The variation in delta C(p)d may
      result from an inherent temperature-dependence of delta C(p)d, since it is
      measured for each mutant over a different temperature range. The thermodynamics
      of denaturation of the disulfide mutant with a crosslink between positions 70 and
      92 change anomalously with pH but in a similar way to that of the D93N mutant of
      barnase, which lacks the D93-R69 salt-bridge present in the wild-type. This
      finding confirms initial observations in the X-ray structure of this disulfide
      mutant that the salt-bridge has been disrupted by the introduced crosslink.

PMID- 9149153
TI  - Assembly of protein tertiary structures from fragments with similar local
      sequences using simulated annealing and Bayesian scoring functions.
AB  - We explore the ability of a simple simulated annealing procedure to assemble
      native-like structures from fragments of unrelated protein structures with
      similar local sequences using Bayesian scoring functions. Environment and residue
      pair specific contributions to the scoring functions appear as the first two
      terms in a series expansion for the residue probability distributions in the
      protein database; the decoupling of the distance and environment dependencies of
      the distributions resolves the major problems with current database-derived
      scoring functions noted by Thomas and Dill. The simulated annealing procedure
      rapidly and frequently generates native-like structures for small helical
      proteins and better than random structures for small beta sheet containing
      proteins. Most of the simulated structures have native-like solvent accessibility
      and secondary structure patterns, and thus ensembles of these structures provide
      a particularly challenging set of decoys for evaluating scoring functions. We
      investigate the effects of multiple sequence information and different types of
      conformational constraints on the overall performance of the method, and the
      ability of a variety of recently developed scoring functions to recognize the
      native-like conformations in the ensembles of simulated structures.

PMID- 9149154
TI  - The practice of otolaryngology from 1896 to 1996.

PMID- 9149155
TI  - Goodhill V. "Sudden deafness and round window rupture." (Laryngoscope
      1971;81(9):1462-74).

PMID- 9149156
TI  - Victor Goodhill, MD, and perilymph fistula: reflecting on the man and the
      controversy.

PMID- 9149157
TI  - Presidential reflections.

PMID- 9149158
TI  - Celebrating a century of scholarship, leadership, and service.

PMID- 9149159
TI  - Image-guided endoscopic surgery: results of accuracy and performance in a
      multicenter clinical study using an electromagnetic tracking system.
AB  - Image-guided surgery has recently been described in the literature as a useful
      technology for improved functional endoscopic sinus surgery localization. Image
      guided surgery yields accurate knowledge of the surgical field boundaries,
      allowing safer and more thorough sinus surgery. We have previously reviewed our
      initial experience with The InstaTrak System. This article presents a multicenter
      clinical study (n=55) that assesses the system's capability for localizing
      structures in critical surgical sites. The purpose of this paper is to present
      quantitative data on accuracy and performance. We describe several new advances
      including an automated registration technique that eliminates the redundant
      computed tomography scan, compensation for head movement, and the ability to use
      interchangeable instruments.

PMID- 9149160
TI  - Clinical pathways in acoustic tumor management.
AB  - Clinical pathways are tools for cost containment and quality improvement in the
      managed care environment. This report describes our experience with developing
      and implementing a clinical pathway for acoustic neuroma surgery. Intensive care
      unit bed days and inpatient hospitalization days for cerebellopontine angle
      surgery significantly decreased during the months that the pathway was developed,
      and the incidence of complications was unchanged after adoption of the algorithm.
      We conclude that with joint neurootology and neurosurgery leadership clinical
      pathways can be a safe, cost-effective, and clinically useful technique in
      acoustic neuroma surgery in a managed care setting. As this management scheme
      evolves, surgeons must take the leadership to ensure that decisions are based on
      clinically relevant parameters.

PMID- 9149161
TI  - Benign paroxysmal positional vertigo.
AB  - Benign paroxysmal positional vertigo (BPPV) has received renewed clinical
      interest. At the Johns Hopkins Otological Vestibular Laboratory, 781 patients
      were tested on more than one occasion between September 1976 and November 1992.
      Of these patients, 187 (24%) were found to have positional nystagmus consistent
      with a diagnosis of BPPV. A retrospective analysis of these patients' records,
      including vestibular test and eye movement reports, audiograms, questionnaires,
      and hospital charts was performed. After this review, the nystagmus, initially
      diagnosed as due to BPPV, was believed to be a manifestation of another disease
      process in 36 cases. Of the remaining 151 cases, 52 (34%) presented with no
      significant preceding disorder and have been termed primary BPPV. In the
      remaining 99 patients we found coexisting or associated disorders which included
      Meniere's disease, head trauma, prior ear surgery, vestibular neuronitis,
      migraine, and others. Forty-five of these 151 patients (31%) had an associated
      diagnosis of Meniere's disease. To our knowledge a significant association
      between Meniere's disease and BPPV has not been reported. A review of the
      literature with discussion of BPPV and the associated disorders is offered.

PMID- 9149163
TI  - Mucosal injuries of the upper aerodigestive tract after smoking crack or freebase
      cocaine.
AB  - The introduction of "crack" and 'freebase" cocaine to the United States has
      resulted in an increased number of patients presenting to emergency rooms with
      cocaine-related burns of the upper aerodigestive tract. Because symptoms are
      nonspecific and histories often unreliable, the emergency room physician must
      keep a high index of suspicion for cocaine use when confronted with these types
      of patients. We present seven patients who had burns to the upper aerodigestive
      tract as a result of smoking crack or freebase cocaine. Two of seven patients
      underwent an emergency tracheotomy, probably because of delayed diagnosis and
      inadequate early medical intervention. This article reviews the history behind
      cocaine use, its different modes of administration, potential complications
      associated with smoking cocaine, diagnostic workup, and treatment options.

PMID- 9149162
TI  - Midline glossectomy and epiglottidectomy for obstructive sleep apnea syndrome.
AB  - Obstructive sleep apnea syndrome is caused by narrowing of the pharyngeal airway
      and loss of dilator tone during sleep. In patients with severe apnea surgical
      correction often requires attention to both the oropharynx and hypopharynx.
      Tongue reduction surgery has been described for persistent apnea after failure of
      palatal surgery. We describe our experience with midline glossectomy with
      epiglottidectomy in 12 patients with a mean age of 48.8 +/- 14.2 years and body
      mass index of 36.0 +/- 8.8 kg/m2. Response to treatment was defined as a
      postoperative respiratory disturbance index (RDI) below 20. Three patients (25%)
      responded to treatment. The mean apnea index decreased from 48.9 to 35.7, RDI
      decreased from 73.3 to 46.6, and lowest oxygen saturation increased from 65.9 to
      77.9%. RDI in responders decreased from 69.7 to 10. Midline glossectomy with
      epiglottidectomy has variable results, yet is effective in selected patients with
      hypopharyngeal narrowing related to macroglossia.

PMID- 9149165
TI  - Computer-assisted surgery in the frontal and maxillary sinus.
AB  - We report the intraoperative use of bent probes for 3-dimensional computer
      assisted navigation in ENT surgery with the ISG Viewing Wand. Probe calibration
      is standardized and the new probes comply with the overall application accuracy
      of the navigation system. The bent probes permit an easy access to the remotest
      locations of the maxillary and the frontal sinus and are beneficial for
      application in paranasal sinus surgery. We present our clinical experiences with
      these probes.

PMID- 9149164
TI  - Interferon gamma expression in human nasal polyps.
AB  - One feature among nasal polyps (NPs) is the predominance of lymphocytes and
      eosinophils. We hypothesize that elevated levels of interferon gamma (IFN-gamma)
      activate lymphocytes and eosinophils within the NP microenvironment. Nasal polyps
      were evaluated for distribution and levels of IFN-gamma in specimens from 27
      patients with nasal polyposis and 4 controls. Immunohistochemical study revealed
      IFN-gamma staining of eosinophils, glandular cells, and epithelium (27 of 27
      patients). ELISA analysis indicated elevated IFN-gamma levels in total NP tissues
      (25.6 +/- 7.23 pg/mg total protein [TP]) compared with controls (16.27 +/- 6.54
      pg/mg TP). Three subpopulations were identified based on IFN-gamma levels: low
      IFN-gamma group (10.7 +/- 5.51 pg/mg TP); medium IFN-gamma group (25.70 +/- 5.90
      pg/mg TP); and high IFN-gamma group (52.58 +/- 10.29 pg/mg TP). The latter levels
      were approximately 3.5 times the control levels (P<0.0025). Patients with
      previous polypectomy surgery showed higher levels of IFN-gamma compared with
      controls (P<0.0423). A trend was found with increased IFN-gamma levels and
      allergy, asthma, and topical steroid use.

PMID- 9149167
TI  - Intracellular reservoir of Streptococcus pyogenes in vivo: a possible explanation
      for recurrent pharyngotonsillitis.
AB  - Numerous theories have been presented that attempt to explain the frequent
      recurrences of pharyngotonsillitis caused by Streptococcus pyogenes; these
      recurrences occur after seemingly adequate antibiotic treatment. We previously
      have demonstrated that Spyogenes can survive for up to 7 days intracellularly in
      immortalized human respiratory epithelial cells grown in an antibiotic
      supplemented medium. Viable S pyogenes were externalized and established an
      extracellular infection, whenever the extracellular antibiotic was removed. We
      have investigated the presence of intracellular S pyogenes in two in vivo studies
      using respiratory epithelial cells collected from patients with tonsillitis and
      the tonsils of asymptomatic carriers. Electron microscopy and
      immunohistochemistry demonstrated intracellular S pyogenes in pharyngeal
      epithelial cells in 13 of 14 patients with tonsillitis (93%). Furthermore,
      intracellular S pyogenes were found in macrophage-like cells in eight (73%) and
      in epithelial cells in four (36%) tonsils from 11 asymptomatic S pyogenes
      carriers. These in vivo data strongly support the hypothesis that intracellular S
      pyogenes can constitute a reservoir of bacteria with the potential to cause
      reinfections.

PMID- 9149166
TI  - Immune responses against Streptococcus pyogenes in human palatine tonsils.
AB  - We investigated cellular immunity against Streptococcus pyogenes in human tonsils
      by measuring antigen-specific immunoglobulin-secreting cells and the production
      of cytokines from CD4+ T cells in response to M proteins. The incidence of S
      pyogenes in tonsils was significantly higher in patients with recurrent
      tonsillitis (RT) than in patients with tonsillar hypertrophy (TH). M protein
      specific immunoglobulin A (IgA) and immunoglobulin G spot-forming cells were
      increased in patients with RT compared with patients with TH. In RT the number of
      M protein-specific IgA spot-forming cells was significantly greater in the S
      pyogenes-negative subjects than in the S pyogenes-positive subjects.
      Proliferation of CD4+ T cells and production of interferon-gamma (IFN-gamma) and
      interleukins -2, -4, -5, and -6 (IL-2, IL-4, IL-5, and IL-6) from those T cells
      were observed in response to M protein. The concentrations of IFN-gamma and IL-4
      were higher in RT than in TH. These findings suggest that S pyogenes is
      associated with the pathogenesis of RT and that immune responses against M
      protein may play an important role in preventing the colonization of this
      bacteria in tonsils.

PMID- 9149168
TI  - Final results of a randomized trial comparing chemotherapy plus radiotherapy with
      chemotherapy plus surgery plus radiotherapy in locally advanced resectable
      hypopharyngeal carcinomas.
AB  - After neoadjuvant chemotherapy, a routine conservative approach followed by
      salvage surgery was evaluated in terms of local control and survival in cases of
      advanced potentially resectable hypopharyngeal carcinoma. Between 1985 and 1989,
      92 patients with T3 or T4-NO,N3 operable squamous cell hypopharyngeal carcinomas
      received three courses of neoadjuvant chemotherapy every 2 weeks involving a
      combination of cisplatin, 100 mg/m2, on day 1 and fluorouracil, 1 g/m2, on days 2
      to 5, followed by total laryngopharyngectomy plus postoperative radiotherapy in
      47 patients (arm A) or radiotherapy alone in 45 patients (arm B). Randomization
      was always performed prior to chemotherapy. The response rates of tumor and node
      to chemotherapy were, respectively, 67% in arm A versus 79% in arm B (P > 0.05)
      and 54% in arm A versus 73% in arm B (P > 0.05). Grade III or IV toxicity was
      similar, affecting 15% of patients and 7% of cycles in arm A versus 16% of
      patients and 6% of cycles in arm B. After a mean follow-up of 92 months, survival
      was statistically better (P = 0.04) in arm A (5-year overall survival, 37%;
      median survival, 40 months) than in arm B (19% and 20 months) because of a better
      local control rate (63% versus 39%; P < 0.01). Better results were obtained for
      mutilant surgery in terms of local control and overall survival, regardless of
      response to neoadjuvant chemotherapy.

PMID- 9149169
TI  - Characterization of novel cell lines from pleomorphic adenomas of the parotid
      gland established in a collagen gel system.
AB  - The pathobiology of salivary neoplasms can best be studied in a model system that
      reflects the native state of the tumor. The present study describes the use of a
      three-dimensional collagen gel (organoid) system in which pleomorphic adenomas of
      the parotid gland were propagated in vitro. Five pleomorphic adenoma cultures
      were established as organoid gels and compared with touch-preparations or
      cryopreserved specimens of native tumor. The organoid cultures demonstrated
      normal DNA content, the expression of myoepithelial cell proteins, and the
      production of sulfated acid mucins; these cellular and secretory features
      mimicked those found in the archival specimens. Further, organoid cultures of
      pleomorphic adenoma could be initiated after monolayer culture, demonstrating
      that culture on a plastic support does not alter the nature of the cells.
      Development of an in vitro culture system that maintains the native state of
      pleomorphic adenoma is an important tool for studying the pathobiology of these
      tumors.

PMID- 9149170
TI  - Carotid resection and reconstruction for advanced cervical cancer.
AB  - Patients with advanced cervical cancers often have direct invasion of their
      carotid arteries. The prognosis for these patients with nonsurgical therapy is
      extremely poor. Because complete tumor removal is the only therapy that can offer
      these patients a chance for cure, carotid resection should be performed. We
      performed carotid resection and reconstruction on nine patients with advanced
      cervical cancers. Of these patients, none suffered from severe neurologic
      postoperative complications such as permanent hemiplegia. Three of the nine
      patients have been disease free for more than 24 months. These three patients
      would not have survived without carotid resection. Further study will show the
      usefulness of carotid resection and reconstruction in decreasing the morbidity
      and mortality in patients with cervical cancer involving the carotid artery.

PMID- 9149171
TI  - Contralateral external carotid-middle cerebral artery bypass for carotid artery
      resection.
AB  - Resection of the common carotid or internal carotid artery is occasionally
      unavoidable in cases of advanced head and neck carcinoma with carotid artery
      involvement. To prevent the consequent decrease in cerebral perfusion, we have
      developed a contralateral external carotid-middle cerebral artery bypass grafting
      technique. From 1990 through 1995, six patients with advanced head and neck
      cancer involving the carotid artery underwent total tumor resection combined with
      vascular reconstruction using the contralateral external carotid- middle cerebral
      artery bypass grafting. No bypass-related complications occurred in any patient
      postoperatively. Cerebral hemodynamics after surgery indicated that this bypass
      graft worked steadily over a long term and supplied sufficient volume of blood to
      the cerebral cortex on the opposite side in every case.

PMID- 9149172
TI  - An increase in laryngeal aerosol deposition by ultrasonic nebulizer therapy with
      intermittent vocalization.
AB  - In acute or chronic laryngitis as well as pharyngitis, nebulization with steroid
      and antibiotics is considered to be a safe and effective treatment. However, the
      optimal dose, frequency, duration, and method of administration by ultrasonic
      nebulization is not known. To evaluate whether there is continual improvement
      using ultrasonic nebulizer therapy, the deposition rate of aerosol particles into
      the upper airway was studied. We analyzed the deposition rate in the upper airway
      by a counting system of radioactive isotope (99mTc-diethylene triaminepentaacetic
      acid; 99mTc DTPA). Volunteers in good health inhaled an aerosol containing 99mTc
      DTPA under various conditions of inhalation. Deep and slow inhalation at a
      respiratory rate of 12 breaths/minute resulted in a high deposition rate of 99mTc
      DTPA in the lung and a low deposition rate in the larynx. In contrast, faster
      inhalation at a respiratory rate of 36 breaths/minute resulted in an increase in
      the isotope deposition rate in the larynx. Furthermore, when the volunteers
      vocalized intermittently during the fast inhalation at a respiratory rate of 36
      breaths/minute, the isotope deposition rate in the volunteer's larynx was higher
      than in all other inhalation conditions. These results suggest that fast
      inhalation with intermittent vocalization is one of the important inhalation
      methods used to improve the deposition rate of aerosol particles into the upper
      airway with an ultrasonic nebulizer.

PMID- 9149174
TI  - Nonseptic lateral sinus thrombosis: the otolaryngologic perspective.
AB  - Nonseptic lateral sinus thrombosis (NSLST) differs from septic lateral thrombosis
      (SLST) in that it is not associated with ear or sinus infection, it usually
      occurs in the adult population, and it has an ambiguous clinical presentation.
      The otolaryngologist is often consulted about diagnostic findings associated with
      lateral sinus thrombosis. We report three cases of NSLST that required
      otolaryngologic assessment. The patients were women, ages 23 to 31 years.
      Presenting symptoms were headaches in all three patients; one also had
      concomitant ear pain. Two patients had negative head computed tomography scans;
      only magnetic resonance imaging was diagnostic. Treatment of NSLST consists of
      anticoagulation and elimination of predisposing factors. Familiarity with this
      condition is fundamental for early diagnosis and initiation of appropriate
      therapy. We discuss the origins and causes of NSLST, clinical presentation,
      preferred diagnostic strategy, and treatment alternatives.

PMID- 9149173
TI  - Posterior glottic stenosis mechanism and surgical management.
AB  - Posterior glottic stenosis with arytenoid fixation is an uncommon complication of
      laryngeal injury. Though etiologies vary; the most common is prolonged
      intubation. Patients with this problem are tracheotomy dependent and have
      compromised voice production. There has been no acceptable approach to
      reconstruction of the larynx, the majority of patients being treated with some
      type of vocal fold lateralization. The success rate with this approach varies,
      and this procedure does not take advantage of the intact neuromuscular status of
      the larynx. Over the past 3 years we have utilized an alternative approach, to
      repair the stenosis and mobilize the arytenoids in 10 patients. Our surgical
      technique involves laryngeal exposure via a laryngofissure, the removal of
      posterior glottic cicatricial tissues, and the application of an autologous
      graft. Subsequently, all but one of the patients were able to be decannulated.
      Subjective postoperative voice analysis showed improved voice production. The
      pathophysiology for this disorder and a review of different treatment modalities
      are discussed.

PMID- 9149175
TI  - Compositional differences between bilateral middle ear effusions in otitis media
      with effusion: evidence for a different etiology?
AB  - The aim of this study was to clarify the site of primary pathology in otitis
      media with effusion. Effusions were collected from 64 children with bilateral
      effusions at the time of myringotomy. The rheological properties and biochemical
      compositions of effusions were measured for 23 pairs of effusions, and the levels
      of the inflammatory mediators TNF alpha, IL-1beta, and IL-8 were measured in 41
      pairs using specific enzyme-linked immunosorbent assays (ELISAs). Measurements
      from paired ears were compared using analysis of variance (ANOVA) tests and
      significant differences were found for reduced specific viscosity, mucin content,
      protein content, and levels of IL-8. The results demonstrate that the two ears
      have different immunological processes or rates of processes which might explain
      the significantly different rheological properties of effusions. This suggests
      that each ear undergoes pathological changes independently and has implications
      for using the opposite ear as a control in clinical trials.

PMID- 9149176
TI  - Advancing ear, nose, and throat computer-assisted surgery with the arm-based ISG
      viewing wand: the stereotactic suction tube.

PMID- 9149177
TI  - Reconstruction after infrastructure maxillectomy using dual free flaps.

PMID- 9149178
TI  - Searching for the ulcerative colitis genes.

PMID- 9149179
TI  - Protein-calorie malnutrition and the etiology of cirrhosis.

PMID- 9149180
TI  - Guidelines for the diagnosis and management of Clostridium difficile-associated
      diarrhea and colitis. American College of Gastroenterology, Practice Parameters
      Committee.
AB  - Guidelines for clinical practice are intended to suggest preferable approaches to
      particular medical problems as established by interpretation and collation of
      scientifically valid research, derived from extensive review of published
      literature. When data are not available that will withstand objective scrutiny, a
      recommendation may be made based on a consensus of experts. Guidelines are
      intended to apply to the clinical situation for all physicians without regard to
      specialty. Guidelines are intended to be flexible, not necessarily indicating the
      only acceptable approach, and should be distinguished from standards of care that
      are inflexible and rarely violated. Given the wide range of choices in any health
      care problem, the physician should select the course best suited to the
      individual patient and the clinical situation presented. These guidelines are
      developed under the auspices of the American College of Gastroenterology and its
      Practice Parameters Committee. These guidelines are also approved by the
      governing boards of American College of Gastroenterology and Practice Parameters
      Committee. Expert opinion is solicited from the outset for the document.
      Guidelines are reviewed in depth by the committee, with participation from
      experienced clinicians and others in related fields. The final recommendations
      are based on the data available at the time of the production of the document and
      may be updated with pertinent scientific developments at a later time. The
      following guidelines are intended for adults and not for pediatric patients.

PMID- 9149181
TI  - Delayed gastric emptying and postoperative ileus after nongastric abdominal
      surgery: part I.

PMID- 9149182
TI  - Gastrointestinal manifestations of progressive systemic sclerosis.
AB  - Management of patients with progressive systemic sclerosis requires a thorough
      gastroenterological examination and a profound knowledge of possible
      gastrointestinal manifestations of the disease. The esophagus is the
      gastrointestinal segment most often involved. Smooth muscle atrophy leads to a
      loss of esophageal peristalsis, a defect of the lower esophageal sphincter, and
      gastric hypomotility, thus predisposing to severe reflux esophagitis. A rational
      diagnostic approach includes standard manometry and endoscopy. The prevention of
      strictures is the main aim of therapeutic efforts that may consist of lifestyle
      changes, prokinetic drugs, long-term application of proton pump inhibitors, and,
      if inevitable, surgical intervention. Involvement of the small intestine and
      colon is less common but may lead to life-threatening complications like chronic
      pseudoobstruction or pneumatosis cystoides intestinalis. The main therapeutic
      options consist of antibiotics for bacterial overgrowth and nutritional
      supplementation. Recently, a preliminary study with octreotide yielded promising
      results. Anorectal dysfunction can lead to fecal incontinence or rectal prolapse.

PMID- 9149183
TI  - HLA association and occurrence of autoantibodies in Asian-Indian patients with
      ulcerative colitis.
AB  - OBJECTIVES: The purpose of the present study was to determine the profile of HLA
      class I antigens, antinuclear antibodies (ANA), and antineutrophil cytoplasmic
      antibodies (ANCA) in ulcerative colitis (UC) patients from Northern India.
      METHODS: The study consisted of 100 UC patients with or without extraintestinal
      manifestations. Data on HLA, ANA, and ANCA were analyzed with respect to age at
      onset, sex, duration of disease, and occurrence of extraintestinal
      manifestations, and data were correlated with those of healthy controls from the
      same population. RESULTS: The most common extraintestinal manifestations in order
      of occurrence were arthralgia (53.8%), ocular lesions (18%), sacroiliitis
      (12.7%), hepatobiliary (7.7%), cutaneous (5%), and vascular (2.6%). ANA and ANCA
      were positive in only 3% of cases. Of the HLA class I antigens, HLA-A19 was
      significantly increased in UC patients compared with controls (63.4% vs. 33.5%, p
      < 0.001, RR = 3.4), particularly its subtype HLA-A33 (20.7% vs. 4%, p < 0.001, RR
      = 6.3). There was no deviation in the frequency of HLA-B locus antigens, whereas
      HLA-Cw6 was increased significantly in patients compared with controls (14.6% vs.
      3.5%, p < 0.001, RR = 4.4). CONCLUSIONS: The occurrence of extraintestinal
      manifestations in Indian patients with UC is similar to that reported elsewhere,
      although ANA and ANCA positivity is lower. HLA studies revealed that A19(33) and
      Cw6 are associated with UC.

PMID- 9149184
TI  - Dietary and nutritional abnormalities in alcoholic liver disease: a comparison
      with chronic alcoholics without liver disease.
AB  - OBJECTIVE: To document the profile and role of malnutrition in alcoholic
      hepatitis, compared with chronic alcoholics and nonalcoholic chronic liver
      disease. METHODS: To this end, we studied 67 patients with alcoholic liver
      disease (ALD) (group I), 52 chronic alcoholics without histological evidence of
      liver disease (group II), 44 nonalcoholic cirrhotics (group III), and 52 healthy
      controls (group IV). Alcoholic and nonalcoholic calories were calculated and
      percentage dietary and nutritional deficiencies computed. Anthropometric indices,
      nitrogen balance, and immune status of the patients were assessed. RESULTS:
      Alcohol constituted about 48% of daily caloric intake in patients with ALD. The
      percentage mean intake of carbohydrate, protein, and energy was decreased in all
      three study groups compared with controls. The deficiencies were more pronounced
      in patients with severe than with moderate ALD. These deficiencies were more
      severe in the group III patients. Whereas body fat stores were maintained in
      groups I and II, reduction in lean body mass and serum transferrin was
      significant in patients in groups I and III. In group II patients compared to
      group I patients, the body mass index (19.9 +/- 4.0 vs. 22.3 +/- 3.4) and triceps
      skinfold thickness (6.1 +/- 4.8 vs. 10.2 +/- 5.6 mm) were significantly lower.
      CONCLUSIONS: 1) protein energy malnutrition is common in both alcoholic and
      nonalcoholic cirrhotics, but is more pronounced in the latter; 2) the degree and
      profile of malnutrition in chronic alcoholics and in alcoholic cirrhotics are
      comparable; 3) based on our results, we hypothesize that malnutrition may not
      play a primary role in the pathogenesis of ALD.

PMID- 9149185
TI  - Hereditary hemochromatosis: presentation and diagnosis in the 1990s.
AB  - OBJECTIVES: In the past, patients with hereditary hemochromatosis have been
      identified predominantly from symptomatic presentation or from family studies. In
      the 1990s, iron studies on routine screening chemistry panels have become more
      commonplace. The purpose of this paper is to describe the clinical, laboratory,
      and presenting features of a series of patients with hereditary hemochromatosis,
      diagnosed from 1990 to 1995. METHODS: Clinical information, serum and liver iron
      studies, liver histology, and phlebotomy requirements were evaluated in 40
      patients with newly diagnosed hereditary hemochromatosis prospectively referred
      to a tertiary university-based hepatology clinic. RESULTS: Eighty-three percent
      of patients came to medical attention as a result of screening blood work: 73%
      were asymptomatic and 78% had normal physical examinations. Only three patients
      had cirrhosis from hemochromatosis alone, only two were diabetic, and only two
      had increased skin pigmentation. These findings are in contrast to previous
      reports of hemochromatosis probands in which patients with symptoms and more
      advanced disease were identified. The hepatic iron concentration, hepatic iron
      index, and age at diagnosis were similar for men and women. CONCLUSIONS: With the
      use of screening iron studies on routine serum chemistry panels, patients with
      hemochromatosis can be identified and subsequently treated before they have
      symptoms or organ damage.

PMID- 9149186
TI  - Does pretreatment with omeprazole decrease the chance of eradication of
      Helicobacter pylori in peptic ulcer patients?
AB  - OBJECTIVE: It has been reported that pretreatment with omeprazole could decrease
      the efficacy of Helicobacter pylori eradication. Our aim was to compare the
      efficacy, safety, and tolerability of the eradicating regimen,
      omeprazole/amoxicillin/metronidazole. The two antibiotics were scheduled either
      during the first or during the last 2 wk of omeprazole administration. METHODS:
      In this prospective controlled study conducted in a single center, 78 symptomatic
      peptic ulcer patients were treated for 4 wk with omeprazole 40 mg o.m.; the
      patients were randomly assigned to receive amoxicillin 1 g t.i.d. postprandially
      and metronidazole 250 mg t.i.d. postprandially, either during the first 2 wk
      (group A, n = 40) or the last 2 wk of therapy with omeprazole (group B, n = 38).
      H. pylori status was assessed by culture, histology, urease test, and IgG
      antibodies. Each patient's course was followed for 1 yr. RESULTS: H. pylori
      infection was cured in 97.4% of group A (95% CI: 0.84-0.99) and in 89% of group B
      (95% CI: 0.73-0.96, p = 0.28). Healing was achieved in 80% of the patients in
      group A (95% CI: 0.63-0.90) and in 75.7% of patients in group B (95% CI: 0.60
      0.90, p = 0.60) At 12-month follow-up, 72 patients were evaluated: 37/38 (97%) of
      patients in group A and 33/33 (100%) in group B were confirmed as cured of the
      infection (NS). Peptic ulcer healing rate reached 100% in the two groups.
      Furthermore, between the two groups, there were no significant differences in
      symptom relief or improvement. Both regimens were well tolerated, and no patient
      had to be withdrawn from therapy because of an adverse event. Minor side-effects
      appeared to be similar in the two groups (40% vs. 38%). CONCLUSIONS: This
      randomized study clearly indicates that omeprazole pretreatment does not
      significantly reduce the efficacy of eradicating therapy for H. pylori in peptic
      ulcer patients.

PMID- 9149187
TI  - Gastric metaplasia and Helicobacter pylori.
AB  - OBJECTIVES: We investigated the relationships between gastric metaplasia
      occurring during the healing and scarring stages of duodenal ulcers and
      Helicobacter pylori by examining the course of gastric metaplasia in H. pylori
      eradicated and non-eradicated patients. METHODS: One hundred and six H. pylori
      positive patients with active duodenal ulcers were assigned to either a non
      eradication group or an eradication group. The non-eradication group received
      lansoprazole for 6 wk, followed by an H2-receptor antagonist. The eradication
      group also received amoxicillin and metronidazole for 1 wk, in addition to
      lansoprazole, after initial endoscopic examination. In both groups, biopsy
      specimens were obtained from the ulcer margin in the active stage and from the
      center of the scar in the scarring stage. Specimens were examined microscopically
      as well as by rapid urease test to assess the extent of gastric metaplasia and to
      detect the presence of H. pylori. RESULTS: The extent of gastric metaplasia
      increased as the ulcers healed. The extent of gastric metaplasia was of a lesser
      degree in the non-eradication group than in the eradication group at the time of
      healing, and this tendency became increasingly apparent in the course of follow
      up, resulting in reduced defense mechanisms against acidity to promote the
      recurrence of ulcers. In the eradication group, among those in whom eradication
      was successful, gastric metaplasia presented a well-developed appearance with
      abundant intracellular mucus and remained in this condition for a prolonged
      period, resulting in adequate defense mechanisms against acidity to prevent the
      recurrence of ulcers. CONCLUSION: By the eradication of H. pylori, gastric
      metaplasia becomes well-developed and remains so for a prolonged period. Thus,
      the eradication of H. pylori appears to play a role in the prevention of ulcer
      recurrences by developing adequate defenses against acidity.

PMID- 9149189
TI  - Clinical and endoscopic risk factors in the Mallory-Weiss syndrome.
AB  - OBJECTIVES: Although patients with bleeding Mallory-Weiss tears are generally
      hospitalized, we wished to develop guidelines facilitating the selection, by
      clinical and endoscopic criteria, of patients who do not need hospitalization.
      Our specific aims were to determine whether presenting manifestations of bleeding
      differed in hemodynamically unstable patients, whether active bleeding or
      stigmata of bleeding at endoscopy were prognosticators for significant
      rebleeding, and the outcomes in endoscopically managed patients. METHODS: The
      endoscopic and clinical features of all patients with acute GI bleeding from a
      Mallory-Weiss tear were obtained from our GI Bleeding Team database over a
      consecutive 4-yr period and analyzed for prognostic indicators. RESULTS: 1)
      Presenting manifestations, e.g., hematochezia, were significantly different in
      hypotensive patients. 2) Active bleeding but not stigmata was associated with
      higher transfusion requirements. 3) Rebleeding was unusual, occurring within 24
      h, more often in patients with a bleeding/coagulation diathesis. The median
      hospital stay was 4 days (range 1-24). Fifty-seven percent of patients received
      transfusion (median 4 units, range 1-26 units); requirements were higher in
      patients with coagulopathies. CONCLUSIONS: Patients without risk factors for
      rebleeding (portal hypertension, coagulopathy), clinical features indicating
      severe bleeding (hematochezia, hemodynamic instability), or active bleeding at
      endoscopy can be managed with a brief period of observation. Patients with
      endoscopically active bleeding may benefit from endoscopic therapy.

PMID- 9149188
TI  - Mucosa-associated lymphoid tissue (MALT) in Barrett's esophagus: prospective
      evaluation and association with gastric MALT, MALT lymphoma, and Helicobacter
      pylori.
AB  - OBJECTIVES: Prospective evaluation of the prevalence of mucosa-associated
      lymphoid tissue (MALT) within Barrett's esophagus and its association with
      gastric MALT, gastric MALT lymphoma, and H. pylori infection. METHODS: From
      Barrett's esophagus patients, a minimum of six gastric biopsies were obtained, in
      addition to Barrett's surveillance biopsies. Additional gastric biopsies were
      taken from any ulcer(s), nodule(s), polyp(s), or other lesions. Patients with
      gastroesophageal reflux symptoms without Barrett's esophagus served as controls.
      RESULTS: One hundred and thirty-nine Barrett's patients were included in the
      study. One hundred and twenty-two of these patients had gastric biopsies for
      gastric MALT and H. pylori determination. H. pylori was noted in the stomach of
      48 patients and within Barrett's mucosa in 14. Barrett's MALT was noted in seven
      cases, gastric MALT in 16, and gastric MALT lymphoma in two. None of the 101
      control patients had esophageal MALT. Two of the seven patients with Barrett's
      MALT had gastric MALT. Barrett's MALT was associated with esophageal H. pylori in
      57.1% cases and gastric H. pylori in 71.4%. The prevalence of gastric and
      esophageal H. pylori in patients with Barrett's MALT was significantly higher
      compared to patients with Barrett's without MALT (p < 0.0001 and p < 0.007,
      respectively). Barrett's MALT was very focal and its esophageal location
      variable. CONCLUSIONS: Barrett's MALT was associated with both esophageal and
      gastric H. pylori colonization. Esophageal MALT was associated with Barrett's
      esophagus. Gastric biopsy sampling is warranted in any patient with Barrett's
      MALT to detect gastric MALT and H. pylori, which, if found, should be eradicated.

PMID- 9149190
TI  - Randomized, controlled comparison of two forms of preparation for screening
      flexible sigmoidoscopy.
AB  - OBJECTIVE: There is a paucity of data regarding the optimal form of bowel
      preparation for flexible sigmoidoscopy. Most endoscopists recommend enemas. A
      simpler preparation that is easy, acceptable, and that reduces patient encounter
      time would be desirable, and might be cost-effective. Our objective in this study
      was to evaluate a simple oral form of preparation for screening flexible
      sigmoidoscopy. METHODS: In this randomized, single-blind, controlled trial, we
      compared two forms of preparation in consecutive male patients referred for
      screening flexible sigmoidoscopy. The oral preparation consisted of one bottle of
      magnesium citrate and two "Dulcolax" tablets on the evening before flexible
      sigmoidoscopy. This was compared with the standard form of preparation, namely,
      two Fleet's enemas given on arrival at the endoscopy suite. Thirty-seven patients
      received the oral preparation [mean age, 62.8 +/- 8.9 (SD) yr]; 33 received
      enemas (mean age, 65.2 +/- 7.3 yr). Endoscopists were blinded to the preparation.
      RESULTS: Mean time between arrival and starting flexible sigmoidoscopy was 36 +/-
      22 (SD) min for patients on oral preparation, and 62 +/- 25 min for patients
      receiving enemas (p < 0.0001). Mean times performing flexible sigmoidoscopy were
      10 +/- 3 min and 13 +/- 4 min, respectively (p = 0.004). Mean patient
      satisfaction score (range 0-13) was higher for patients given the oral
      preparation (11.4 +/- 1.8) than for patients receiving enemas (9.6 +/- 2.4) (p =
      0.001). Fifteen patients randomized to receive the oral preparation had previous
      flexible sigmoidoscopy with an enema preparation; all preferred the oral form.
      Mean technical difficulty (range 1-10) was 3 +/- 2.2 for patients given the oral
      preparation and 4.9 +/- 3.1 for patients receiving the enema preparation (p =
      0.01). Polyps were identified in 10/37 patients who received the oral preparation
      and in 3/33 patients who received enemas (p = 0.05). Quality of colon preparation
      was judged "good" in 29, "fair" in four, and "poor" in four, among the 37
      patients given the oral form; corresponding values for 33 patients given enemas
      were 16, 10, and 7 (p = 0.03). CONCLUSION: Patient acceptance, encounter time,
      technical ease, and quality of colon preparation were significantly better with
      the oral form of colon preparation than with the standard Fleet enema
      preparation.

PMID- 9149191
TI  - Expandable stents: unusual locations.
AB  - OBJECTIVES: Expandable metallic prostheses have been used widely for malignant
      biliary stenoses and are being used increasingly for malignant dysphagia and
      esophago-airway fistulas. Potentially, such prostheses can be placed for gut
      neoplasms obstructing beyond the esophagus or gastric cardia. This series reports
      our experience with expandable metallic stents in the stomach, jejunum, and
      colon. METHODS: All patients with expandable gastrointestinal stents (other than
      biliary tree or esophagus) were reviewed. Indications for stent placement, type
      and location of prosthesis, patient demographics, procedural problems, and data
      with regard to outcome were defined. RESULTS: Over a 6-yr period, expandable
      prostheses (Z stent, Esophacoil, and Ultraflex) were placed in nine patients with
      widespread malignancy (afferent loop obstruction, three; colon obstruction,
      three; gastric outlet obstruction, two; and esophagojejunal interposition
      stricture, one). There was one colon perforation as a consequence of dilation
      prior to placement of the prosthesis. Subsequent problems included migration
      (one), occlusion by food bolus (one), and tumor overgrowths/ingrowths (three)
      which were treated with laser. Median survival approximated 9 months.
      CONCLUSIONS: Expandable metallic prostheses have the potential to palliate
      malignant gastrointestinal stenoses that have traditionally been treated with
      surgical bypass or comfort care measures only.

PMID- 9149192
TI  - 5-Aminosalicylates, sulfasalazine, steroid use, and complications in patients
      with ulcerative colitis.
AB  - OBJECTIVES: The choice between sulfasalazine and 5-aminosalicylate (5-ASA) drugs
      in the management of patients with ulcerative colitis often depends on
      idiosyncrasies of drug tolerance and control of the disease in individual
      patients. We sought to evaluate whether there were population differences in the
      effect of 5-ASA and sulfasalazine on the occurrence of clinically recognized
      adverse events. We also attempted to determine whether there were differences in
      the use of concomitant steroids and in the rates of hospitalization. METHODS: We
      reviewed a large computerized database drawn from general practices in the United
      Kingdom. There we found records of 2894 patients in whom general practitioners
      had diagnosed ulcerative colitis, and who were receiving ongoing medical therapy
      specific to ulcerative colitis. The period of data availability ran from the
      beginning of 1990 to the latter part of 1993. The average duration of observation
      was 2.1 yr per patient. Patient histories were categorized into distinct periods
      according to the dose of 5-ASAs and sulfasalazine, steroids, and
      immunosuppressants, and were further separated according to the activity of
      ulcerative colitis. Within these categories, we examined the initiation and
      discontinuation of steroids, incidence of new hospitalizations for ulcerative
      colitis, and clinical mention of adverse events. RESULTS: New clinical mentions
      of hepatic, pancreatic, renal, and hematological events other than anemia were
      similar among the 5-ASAs and were very infrequent overall. Hospitalizations for
      ulcerative colitis occurred with similar frequency (about 15 hospitalizations per
      100 patients per year) among users of those drugs. Patients receiving
      sulfasalazine had lower rates of initiation of prednisolone than did patients
      receiving 5-ASA, but sulfasalazine was used proportionately less often in
      patients who had been recently hospitalized, and it may be that sulfasalazine
      patients were somewhat less sick, overall, than were 5-ASA-using patients. The
      choice of drug did not affect discontinuation rates for prednisolone among
      established users. CONCLUSIONS: In the United Kingdom, during the period of this
      study, serious adverse reactions to drugs were not an important aspect of the
      management of patients with ulcerative colitis. Renal and pancreatic
      complications of sulfasalazine and 5-ASA therapy were extremely rare.
      Sulfasalazine and 5-ASA drugs have similar steroid-sparing properties. Disease
      specific hospitalizations are approximately 100 times more common in ulcerative
      colitis patients than are serious adverse drug effects. Considerations of drug
      efficacy should therefore dominate the choice between therapeutic agents.

PMID- 9149193
TI  - Reflux esophagitis after total gastrectomy with jejunal pouch reconstruction:
      comparison of long and short pouches.
AB  - OBJECTIVE: To evaluate the effect of the type of jejunal pouch (long or short) on
      reflux esophagitis after total gastrectomy. METHODS: Two groups of patients who
      underwent jejunal pouch reconstruction (long pouch, n = 9; short pouch, n = 9)
      after total gastrectomy were compared, and each was also compared with a group of
      healthy control subjects (n = 9). Reflux symptoms were assessed using a reflux
      score questionnaire derived from Moran's graded reflux questionnaire.
      Scintigraphy was performed to evaluate quantitatively intestinoesophageal reflux
      and pouch emptying time (t75%). RESULTS: Heartburn was more common in the long
      pouch group than in the short pouch group (56 vs 11%, p < 0.05), and the reflux
      score was significantly higher in the long pouch group (mean score 3.0 vs 1.0, p
      < 0.01). The scintigraphic reflux index in the long pouch group, short pouch
      group, and control group was 9.57 +/- 5.52, 7.05 +/- 3.35, and 1.55 +/- 0.70,
      respectively. The reflux index in the entire group of patients was significantly
      higher than that in the control group (p < 0.005). In addition, t75% was
      significantly longer in the long pouch group (46.0 +/- 16.2 min) than in the
      short pouch group (21.1 +/- 15.39 min). CONCLUSION: Our findings suggest that
      reconstruction with a short jejunal pouch is more effective than a long pouch in
      preventing reflux symptoms.

PMID- 9149194
TI  - Reproducibility of proximal probe pH parameters in 24-hour ambulatory esophageal
      pH monitoring.
AB  - OBJECTIVES: To assess the reproducibility and reliability of the proximal pH
      probe in detecting acid reflux into the proximal esophagus. METHODS: Using dual
      probe ambulatory esophageal pH monitoring, we studied 32 subjects (11 healthy
      control subjects, 10 patients with distal esophageal acid reflux, and 11 patients
      with both distal and proximal esophageal acid exposure) on two separate days
      within a 20-day period. The distal pH probe was placed 5 cm above the
      manometrically determined lower esophageal sphincter, and the proximal probe was
      positioned immediately distal to the upper esophageal sphincter. Patients were
      categorized on the basis of the esophageal pH data obtained during the first
      study. Reflux parameters assessed were the percentages of time in which pH was <4
      in the total, upright, and supine positions. To be considered reproducible, all
      three of the above parameters had to remain in the same category as the first
      day's results. RESULTS: Intrasubject reproducibility of the proximal probe was 91
      100% in healthy subjects, 70-90% in patients with distal esophageal acid reflux,
      and 45-73% in patients with proximal esophageal acid reflux. The proximal probe
      reproducibility for the overall diagnosis of gastroesophageal reflux disease was
      91% in healthy subjects, 70% in patients with distal esophageal acid reflux, and
      only 55% in those with proximal esophageal acid reflux. Statistical analysis
      demonstrated only a fair index of concordance (kappa = 0.40) for the proximal
      probe. CONCLUSIONS: The proximal pH probe has excellent specificity (91%) but
      poorer sensitivity and reproducibility (55%) for identifying abnormal amounts of
      proximal esophageal acid reflux. Therefore, a negative test result does not
      exclude proximal reflux with microaspiration as a cause of atypical reflux
      symptoms.

PMID- 9149195
TI  - Correlation between patterns of antral contractility and gastric emptying of
      radiopaque markers.
AB  - OBJECTIVES: Gastric clearance of radiopaque markers (ROMs) has been proposed as
      an easy and noninvasive technique for assessment of gastric emptying. This study
      was conducted to evaluate the role of antral obliterating contractions in gastric
      emptying of ROMs in healthy volunteers. METHODS: Fifteen healthy volunteers, 12
      males and three females, aged 21-38 yr, were enrolled in this study. Simultaneous
      recording of scintigraphic solid phase gastric emptying, gastric clearance of
      ROMs, and gastric manometry were performed after an overnight fast. The data of
      scintigraphic solid phase gastric emptying were expressed by half-emptying time
      (t1/2). The ROMs remaining in the stomach were counted fluoroscopically 2.5 and
      4.5 h after the test meal. The time for the appearance of antral obliterating
      contractions after the meal was calculated. RESULTS: Six subjects (40%) passed
      all 10 ROMs after 4.5 h of recording. Among these six subjects, five had antral
      obliterating contractions 190-251 min (mean 232.2 +/- 24.3 min) after the test
      meal. There was no significant difference in t1/2 between subjects with or
      without antral obliterating contractions within the 4.5 h of recording.
      CONCLUSIONS: There was a considerable intersubject variation in the time of first
      antral obliterating contraction after the test meal. In the healthy volunteers,
      all ROMs were passed when there was a postprandial antral obliterating
      contraction. However, some of the ROMs still passed from the stomach in the
      absence of antral obliterating contractions.

PMID- 9149196
TI  - Gastric emptying in hyperthyroidism.
AB  - OBJECTIVES: We undertook a prospective study to survey gastric emptying of a
      solid meal in patients with hyperthyroidism until euthyroidism was reached after
      pharmacological treatment with thiamazole. METHODS: Eleven women (aged 33.2 +/-
      3.2 SE yr) with recently diagnosed hyperthyroidism participated in the study.
      Thyroid function parameters and gastric emptying were examined on three
      occasions, before treatment, during the third week of treatment, and after
      euthyroidism was restored. The control group was composed of 12 age-matched
      healthy women (aged 34.5 +/- 2.3 yr). Gastric emptying of a 390-kcal 99mTc
      labeled solid meal was continuously recorded under a gamma camera over 90 min. A
      power-exponential model was used for analysis of the gastric emptying course.
      Three gastric emptying parameters were computed: t1/2, the gastric half-emptying
      time, S, the curve shape parameter, and K, the slope of the curve. RESULTS:
      Pretreatment solid phase gastric emptying of the patients was not statistically
      significantly different from that of the healthy control subjects: t1/2, 82.8 +/-
      4.9 vs 93.5 +/- 6.0 min; S, 0.996 +/- 0.103 vs 1.032 +/- 0.064; and K, 8.42 +/-
      0.47 vs 7.64 +/- 0.39 min(-1) x 10(-3). Gastric emptying during the third week of
      treatment did not change in comparison with pretreatment gastric emptying: t1/2,
      84.3 +/- 8.2 min; S, 1.014 +/- 0.123; and K, 8.92 +/- 1.12 min(-1) x 10(-3). On
      the other hand, a slight increase in rate of gastric emptying was observed after
      the restoration of euthyroidism (t1/2, 74.6 +/- 5.8 min, and K, 9.65 +/- 0.76
      min(-1) x 10(-3), p < 0.05 vs healthy control subjects for both parameters), but
      no significant change was observed in the shape parameter (S, 0.980 +/- 0.066).
      CONCLUSIONS: In women with hyperthyroidism, gastric emptying of solids does not
      differ significantly from that observed in age-matched healthy control subjects
      and remains unaffected during pharmacological treatment. After restoration of
      euthyroidism, a slight but statistically significant increase in the rate of
      gastric emptying occurs in patients as compared with healthy control subjects.

PMID- 9149197
TI  - CO2 provocation of panic: symptomatic and manometric evaluation in patients with
      noncardiac chest pain.
AB  - OBJECTIVES: Occult panic disorder (PD) may underlie 10-43% of chest pain
      syndromes in patients with normal coronary arteries. A variety of agents, such as
      intravenous lactate, oral caffeine, and inhaled CO2, has been identified that may
      provoke panic attacks in susceptible patients. The aims of this study were (1) to
      better define the relationship between noncardiac chest pain syndromes and panic
      disorder; and (2) to assess the diagnostic utility of PD provocative testing with
      inhaled CO2 in eliciting chest pain and/or esophageal manometric disturbances.
      METHODS: Fourteen patients with chest pain syndromes and negative coronary
      angiograms or stress thallium tests were evaluated for PD and underwent (1)
      standard esophageal manometry followed by continuous manometric recording; (2)
      inhalation by face mask of room air or 35% CO2, single blinded, in random order;
      (3) a previously validated Acute Panic Inventory questionnaire administered
      before and immediately after each inhalation; and (4) Tensilon 10 mg i.v.
      administration. RESULTS: Of 14 patients, 8 met DSM-IIIR criteria for panic
      disorder. Mean Acute Panic Inventory scores (reflecting panic symptoms) increased
      significantly after CO2 inhalation relative to room air in all patients. Of 14
      patients, 8 (4 PD, 4 non-PD) experienced chest pain after CO2 inhalation, whereas
      no patient had chest pain after room air inhalation. Of 14 patients, 5 had pain
      with Tensilon (4 of 5 whom responded to CO2). No specific manometric
      abnormalities occurred during any chest pain episode. CONCLUSION: CO2 inhalation
      is as effective as Tensilon in provoking chest pain in patients with noncardiac
      chest pain. The high prevalence of PD in such patients suggests that CO2
      inhalation, a known panicogen, may be useful in evaluating such patients. The
      mechanism of CO2 induced chest pain remains unknown, but does not appear to be
      attributable to demonstrable esophageal motility abnormalities.

PMID- 9149198
TI  - Impaired fibrinolysis and increased protease levels in gastric and duodenal
      mucosa of patients with active duodenal ulcer.
AB  - OBJECTIVES: Cathepsin B and L (cysteine proteases), urokinase- and tissue-type
      plasminogen activators (serine proteases), and type-1 inhibitor are involved in
      gastric mucosal injury. We determined tissue protease levels in duodenal ulcer
      and their relationship to ulcer phase, bleeding tendency, Helicobacter pylori
      infection, and use of H2-blockers. METHODS: Endoscopic biopsies of antral and
      duodenal mucosa were obtained from 61 patients with active or healed duodenal
      ulcer and control subjects. Antigen concentrations were measured by ELISA.
      RESULTS: Significantly higher levels of cathepsins, urokinase-type plasminogen
      activator, type-1 inhibitor, and significantly lower levels of tissue-type
      plasminogen activator were found in active ulcers. Bleeders had the highest
      cathepsins and urokinase-type plasminogen activator levels. Higher levels of
      urokinase-type plasminogen activator, cathepsin B, and type-1 inhibitor were
      observed in Helicobacter pylori-positive patients. CONCLUSIONS: Our results
      suggest that impaired fibrinolysis (tissue-type plasminogen activator),
      intramucosal proteases (cathepsins), tissue remodeling, and angiogenesis
      (urokinase-type plasminogen activator and type-1 inhibitor) are involved in
      duodenal ulcer formation and healing.

PMID- 9149199
TI  - Nonencapsulated, intact omeprazole granules effectively suppress intragastric
      acidity when administered via a gastrostomy.
AB  - Because of its acid-labile nature, omeprazole is usually administered as
      encapsulated enteric-coated granules. The gelatin capsule and acid-resistant
      coating are essential for effective drug absorption and optimal bioavailability.
      OBJECTIVE: This study tested the effectiveness of nonencapsulated, intact
      omeprazole granules in suppressing intragastric acidity when administered through
      a gastrostomy. METHODS: Fourteen male patients with established gastrostomies
      underwent a baseline 24-h intragastric pH monitoring study while off any acid
      suppressing medication. Via the gastrostomy, they then received 7 days of dosing
      with 20 mg omeprazole as intact granules in orange juice. Twenty-four-hour
      intragastric pH monitoring was repeated on the seventh day. RESULTS: Mean
      intragastric pH during the baseline study was 1.8 (+/- SD 0.7). This pH increased
      to 4.9 +/- 0.8 with omeprazole granules (p < 0.0001). Median intragastric pH rose
      from 1.3 to 5.3 (p < 0.0001). During the baseline study, intragastric pH was
      above 3 for 21.2 +/- 14.1%, above 4 for 14.9 +/- 11.0%, and above 5 for 9.5 +/-
      8.4% of the 24-h recording period. Corresponding values after 7 days of
      omeprazole were 80 +/- 15.1%, 72.5 +/- 16.3%, and 59.1 +/- 16.6% (p < 0.0001 for
      each comparison with pretreatment values). CONCLUSION: Omeprazole effectively
      suppresses intragastric acidity when given through a gastrostomy tube as
      nonencapsulated, intact granules.

PMID- 9149201
TI  - Budd-Chiari syndrome: a common complication of Behcet's disease.
AB  - OBJECTIVE: The Budd-Chiari syndrome is characterized by venous outflow
      obstruction of the liver, usually occurring as a consequence of thrombosis of the
      hepatic veins. Vasculitis is a major component of Behcet's syndrome. The aim of
      this study was to determine the incidence of hepatic vein thrombosis in patients
      with Behcet's disease and to estimate the effect of this entity upon the clinical
      features and course of Behcet's syndrome. METHODS: During an 8-yr period from
      1985 to 1994, from a total of 493 patients with Behcet's disease seen at
      Hacettepe University Hospital, the incidence and effect of hepatic vein
      thrombosis on the clinical course of Behcet's syndrome was investigated. The
      hepatic vein thrombosis in each case was documented by hepatic venography and
      confirmed by digital subtraction angiography, computed tomography,
      ultrasonography, and liver biopsy. Coagulation parameters including protein C,
      protein S, and anti-thrombin III levels were easured in each case. The survival
      of cases with Behcet's syndrome complicated by Budd-Chiari syndrome and the
      effect of the Budd-Chiari syndrome on the survival of individuals with Behcet's
      syndrome were determined using the Kaplan-Meier technique. RESULTS: Of the 493
      cases of Behcet's syndrome, 53 (10.8%) were found to have one or more large
      vessel thrombosis. Of these 53 patients, 14 (26.4%) had hepatic vein thrombosis.
      Of these 14 patients, 8 had an additional inferior vena cava thrombosis and 4 had
      portal vein as well as total inferior vena cava thrombosis. Only two patients
      with isolated hepatic vein thrombosis were identified. These two patients and two
      additional patients with hepatic vein thrombosis plus thrombosis of the hepatic
      portion of the inferior vena cava are currently alive. Of the 10 patients with
      total inferior vena cava and hepatic vein thrombosis (4 also had portal vein
      thrombosis), all 10 died with a mean survival of 10.3 months. During the same
      time period, 37 patients obtained from a total of 1494 patients with clinical
      evidence of either portal hypertension, hepatic venous outflow obstruction or
      inferior vena caval obstruction without Behcet's syndrome were found to have a
      Budd-Chiari syndrome. Of these 37 patients, 19 (51%) had an identifiable
      underlying disorder responsible for their hepatic vein thrombosis. CONCLUSION:
      Based upon this experience, it appears as if Budd-Chiari syndrome is a relatively
      frequent complication of Behcet's disease. When individuals with Behcet's
      syndrome have BCS, concurrent thrombosis of the portal vein and inferior vena
      cava are often found, if the patency of these vessels is assessed. The clinical
      course of patients with Behcet's syndrome complicated by Budd-Chiari syndrome is
      poor. The extent of the vascular thrombosis within the inferior vena cava rather
      than the presence of the hepatic vein thrombosis per se is the major determinant
      of survival.

PMID- 9149200
TI  - Cardiovascular and renal effects of low-dose atrial natriuretic peptide in
      compensated cirrhosis.
AB  - OBJECTIVES: Patients with cirrhosis and ascites have high plasma levels of atrial
      natriuretic peptide (ANP). Pharmacological doses of this hormone usually worsen
      systemic hemodynamics of cirrhotic patients. We assessed whether ANP influences
      cardiovascular homeostasis and renal function in patients with compensated
      cirrhosis at plasma levels comparable to those observed in patients with
      cirrhosis and ascites. METHODS: Radionuclide angiocardiography was performed in
      eight compensated cirrhotic patients during placebo (three periods of 15 min
      each) and ANP infusion (2, 4, and 6 pmol/kg.min for 15 min each), together with
      appropriate blood and urine sampling, to evaluate left ventricular diastolic,
      systolic, and stroke volume, heart rate, cardiac output, arterial pressure,
      peripheral vascular resistance, creatinine clearance, urinary sodium excretion,
      plasma renin activity, plasma aldosterone, norepinephrine and hematocrit.
      RESULTS: The infusion increased plasma ANP up to levels (52.03 +/- 2.29 pmol/L)
      comparable with those observed in 35 patients with ascites (46.42 +/- 1.57 pmol/
      L). This increment was associated with significant reductions in left ventricular
      end diastolic volume, stroke volume, cardiac index (from 3.7 +/- 0.7 to 3.1 +/-
      0.5 L/min.m2, p < 0.05) and mean arterial pressure (from 96.7 +/- 6.5 to 88.5 +/-
      9.5 mmHg, p < 0.05), while heart rate and hematocrit significantly increased.
      Peripheral vascular resistance did not change. These hemodynamic effects occurred
      despite significant increases in plasma renin activity and norepinephrine. ANP
      also induced increases in creatinine clearance, urinary sodium excretion, and
      fractional sodium excretion. CONCLUSIONS: Low-dose ANP affected cardiovascular
      homeostasis and renal sodium handling in compensated cirrhosis, suggesting that
      this hormone may be involved in the pathophysiology of systemic hemodynamic and
      renal functional abnormalities of cirrhosis.

PMID- 9149202
TI  - Glycogen content of the donor liver and its relation to postreperfusion hepatic
      energy metabolism.
AB  - OBJECTIVES: Many studies have suggested that glycogen in donor livers is an
      important fuel during cold ischemic time and at reperfusion. However, it remains
      unclear as to whether the depression of glycogen content in the graft results in
      a critical derangement of energy metabolism after reperfusion. The purpose of
      this study was to assess the possible implications of the glycogen concentration
      of donor livers for the hepatic energy metabolism after reperfusion. METHODS: The
      glycogen content of 28 donor livers and the plasma concentrations of metabolic
      substrates were measured during liver transplantation. RESULTS: Gluconeogenesis
      was maintained even in the glycogen-depleted graft at reperfusion. However,
      glycogen-depleted grafts produced more ketone bodies until 24 h after
      reperfusion. Free carnitine concentrations in these patients were significantly
      higher than those in the patients with glycogen-nondepleated grafts until 48 h
      after reperfusion. CONCLUSIONS: A glycogen-depleted liver graft may restore
      essential metabolic function by producing energy substrates through enhanced
      ketogenesis in the postreperfusion period. The enhanced production of carnitine
      by the graft provides a substrate for the production of ketone bodies and thus
      may be relevant to the enhanced ketogenesis.

PMID- 9149203
TI  - Bone mineral density in patients with pancreatic insufficiency and steatorrhea.
AB  - OBJECTIVES: Low bone mineral density (BMD) has been demonstrated in some patients
      with chronic intestinal disorders accompanied by diarrhea and malabsorption.
      However, very few studies have evaluated BMD in patients with pancreatic
      insufficiency due to cystic fibrosis. Our aim was to assess the prevalence and
      severity of bone loss in a cohort of patients with pancreatic insufficiency as a
      consequence of chronic pancreatitis. METHODS: Fourteen patients with chronic
      pancreatitis were studied. All of them presented with severe pancreatic
      insufficiency (secretin test: bicarbonate < or = 40 mEq/L) and steatorrhea (fecal
      fat > 7 g/day) and had been abstinent from alcohol for a median of 2.5 yr (range
      1-15 yr). BMD was measured with a total-body scanner for dual-energy x-ray
      absorptiometry. Results were expressed as T-score (number of SD by which a
      patient density differs from the mean of sex-matched 30-yr-old healthy controls)
      in lumbar spine (L2-L4) and femoral neck. Total serum calcium, 25-(OH)D3,
      alkaline phosphatase, and midmolecular parathyroid hormone were determined.
      RESULTS: Ten patients demonstrated osteopenia (T-score -1 to -2.5) in the lumbar
      spine and in the femoral neck. Three patients displayed osteoporosis (T-score < 
      2.5) in the lumbar spine and two in the femoral neck. Mean T-scores (+/- SEM)
      were -1.44 +/- 0.37 in the lumbar spine and -1.79 +/- 0.27 in the femoral neck.
      Total and ionic serum calcium, serum parathyroid hormone, and alkaline
      phosphatase were in the normal range in all patients. Serum 25-(OH)D3 was below
      normal range in 7 of 12 patients. T-scores of patients with pancreatitis of
      alcoholic etiology (n = 10) were similar to those of nonalcoholic patients (n =
      4). BMD did not correlate with age, bicarbonate secretion, fecal fat excretion,
      stool volume, parameters of mineral metabolism, duration of alcoholism, or mean
      alcohol intake. CONCLUSIONS: Most patients with pancreatic insufficiency as a
      consequence of chronic pancreatitis exhibit osteopenia, and some show evidence of
      osteoporosis. Identifying the intimate mechanisms for low BMD are beyond the
      limitations of the present study. More in-depth metabolic studies are necessary
      to define the pathogenic mechanism of osteopenia associated with chronic
      pancreatic disorders.

PMID- 9149204
TI  - Preoperative assessment of advanced gastric carcinoma using computed tomography.
AB  - OBJECTIVES: The role of computed tomography (CT) for the staging of gastric
      carcinoma is controversial. The purpose of this study was to evaluate the utility
      of CT in assessing the perigastric spread of advanced gastric carcinoma. METHODS:
      The study included 56 patients who underwent dynamic CT and laparotomy for the
      treatment of node-positive gastric adenocarcinoma. Preoperative CT findings were
      compared with surgical findings, and diagnostic accuracy was estimated. RESULTS:
      Sensitivity, specificity, and accuracy of preoperative CT in determining the
      perigastric tumor spreads were 33, 97, and 73% in pancreatic invasion, 36, 97,
      and 70% in level III lymph node involvement, and 89, 98, and 96% in liver
      metastasis. Peritoneal dissemination was not detected in 15 of 56 patients (27%),
      and stage IV disease was not diagnosed correctly in 18 of 40 patients (45%).
      CONCLUSIONS: Radiologists and surgeons must remember that pancreatic invasion,
      extended lymph node metastasis, and peritoneal dissemination are sometimes
      overlooked in CT examination in patients with advanced gastric carcinoma.

PMID- 9149205
TI  - Preliminary report on the use of oral tacrolimus (FK506) in the treatment of
      complicated proximal small bowel and fistulizing Crohn's disease.
AB  - BACKGROUND: Tacrolimus (FK506) has a mechanism of action similar to cyclosporine.
      Unlike standard oral cyclosporine, tacrolimus is well absorbed orally, even from
      diseased small bowel mucosa. OBJECTIVE: To report the use of oral tacrolimus in
      three patients with complicated proximal small bowel or fistulizing Crohn's
      disease as a "bridge" to methotrexate or 6-mercaptopurine. CASE REPORTS: Oral
      tacrolimus was started at doses of 0.15-0.29 mg/kg/day and adjusted to a whole
      blood tacrolimus concentration range of 10-20 ng/ml. Case 1: Gastroenterostomy
      for gastroduodenal Crohn's disease complicated by recurrent gastrointestinal
      hemorrhage from persistent duodenal ulceration. Case 2: Diffuse jejunoileal
      Crohn's disease, seven prior stricturoplasties, and a postoperative small
      intestinal fistula causing an abdominal abscess. Case 3: Perianal and pouch
      vaginal fistulae after colectomy and ileal pouch-anal anastomosis in a patient
      with Crohn's disease. All three patients had good oral absorption of tacrolimus,
      rapid clinical improvement of their Crohn's disease, and began long-term
      remission maintenance treatment with either methotrexate (n = 2) or 6
      mercaptopurine (n = 1). Dose dependent side effects resulting from tacrolimus
      therapy occurred in all three patients (nephrotoxicity, hyperkalemia, diarrhea,
      nausea, flushing, headache, tremor, paresthesias, and insomnia). CONCLUSIONS:
      Oral tacrolimus (0.15-0.29 mg/kg/day) is well absorbed in patients with Crohn's
      disease with proximal small bowel involvement or fistulae and appears to be of
      clinical benefit as a rapidly acting "bridge" to long-term therapy with
      methotrexate or 6-mercaptopurine.

PMID- 9149206
TI  - Crohn's disease and gastrocnemius vasculitis: two new cases.
AB  - We report two cases of gastrocnemius muscle vasculitis revealing Crohn's disease.
      Gastrocnemius muscle biopsy evidenced a necrotizing vasculitis resembling
      panarteritis nodosa in one case; a nonnecrotizing vasculitis was found in the
      other case. Neither of the patients had systemic vasculitic involvement, and the
      muscle disease resembled calf muscle-located panarteritis nodosa. Our literature
      review shows five cases of calf-located myalgia occurring during Crohn's disease
      characterized by heterogenous histopathological findings including vasculitic and
      myositic lesions. Thus, faced with calf-located myalgia with vasculitis or
      myositis, a search for Crohn's disease is probably necessary to determine
      precisely the frequency and the etiopathogenic mechanisms of this association.

PMID- 9149207
TI  - A novel therapeutic approach for rectal varices: a case report of rectal varices
      treated with double balloon-occluded embolotherapy.
AB  - We present a patient with continuous melena, diagnosed as rectal varices
      bleeding. She had a history of esophageal varices, which was treated by
      endoscopic ligation therapy. Eight years after the treatment of esophageal
      varices, the continuous melena began. Colonoscopic examination showed that the
      melena was caused by rectal varices, which were so severe that they could not be
      treated by either endoscopic sclerotherapy or surgical devascularization. Taking
      into considering the overall risk of treating rectal varices, we chose the
      approach of double balloon-occluded embolotherapy (DBOE) with 5% ethanolamine
      oleate with iopamodol as a liquid embolic material. DBOE is one of the
      interventional radiology techniques (Morita et al., Acta Hepatol Jpn 1994;35:109
      120), but in this case was a completely new and novel clinical procedure for
      rectal varices. After the DBOE therapy, the condition of rectal varices was
      markedly improved. Thus, DBOE might be a new tool for treating inoperable rectal
      varices.

PMID- 9149208
TI  - Role of ERCP in the diagnosis of intraductal papillary mucinous neoplasms.
AB  - Mucinous cystic neoplasms of the pancreas may present in a "ductectatic" form,
      which parallels a distinct clinical presentation. We describe six patients with
      this entity termed mucinous ductal ectasia, or intraductal papillary mucinous
      neoplasm. All six patients presented with typical clinical and endoscopic
      findings and subsequently, almost all were found to have mucinous ductal
      cystadenocarcinomas. The endoscopic and pancreatographic findings associated with
      an intraductal papillary mucinous neoplasm are characteristic, unique, and yield
      a high diagnostic accuracy. It is important to recognize these features of
      intraductal papillary mucinous neoplasm since the tumor has a lower malignant
      potential than adenocarcinoma of the pancreas, and surgical resection is curative
      in many cases.

PMID- 9149210
TI  - Spontaneous gallbladder perforation without acute inflammation or gallstones.

PMID- 9149209
TI  - Colonic motility and tone after spinal cord and cauda equina injury.
AB  - AIM: To characterize colonic motility and tone in patients with spinal cord and
      cauda equina injury. METHODS: Barostat-controlled measurements of tone and
      manometric measurements of phasic contractions in the left colon in two patients
      with spinal cord injury. ANALYSIS: Computer based analysis of tone and phasic
      activity; comparison with data from 11 healthy subjects. RESULTS: Both patients
      showed normal fasting tone and decreased postprandial tone in the colon; one had
      markedly decreased phasic contractility in the descending colon, but both had
      normal sigmoid colon motility. CONCLUSIONS: Impaired postprandial tone and phasic
      motor function of the descending colon after spinal cord injury with normal
      sigmoid motility suggests regional differences in the effect of denervation. The
      effect of the level of injury to the neural axis on colonic motor and sensory
      function requires further elucidation.

PMID- 9149211
TI  - Dysphagia from esophageal diverticulosis responding to botulinum toxin injection.

PMID- 9149212
TI  - Transient multiple hepatic nodules with marked infiltration of eosinophils caused
      by ascariasis.

PMID- 9149213
TI  - Mucinous cystadenoma of the appendix causing intussusception in an adult.

PMID- 9149214
TI  - Primary hydatid disease of the pancreas.

PMID- 9149215
TI  - Beneficial effect of lovastatin on sphincter of Oddi dyskinesia in
      hypercholesterolemia and hypertriglyceridemia.
AB  - This report describes an impaired sphincter of Oddi relaxation function in
      relation to hypercholesterolemia and hypertriglyceridemia. As indicated by
      repetitive amyl nitrite-augmented quantitative hepatobiliary scintgraphy,
      normalization of serum lipids by means of diet and a 3-month treatment period
      with 20 mg of lovastatin per day resulted in an improvement of sphincter of Oddi
      relaxation.

PMID- 9149216
TI  - GERD, DGER, or both in Barrett's esophagus?

PMID- 9149217
TI  - Screening interval for colorectal cancer with colonoscopy: the long and short of
      it.

PMID- 9149218
TI  - Subclinical hepatic encephalopathy: how best to diagnose?

PMID- 9149219
TI  - Evaluation of anal sphincter defects.

PMID- 9149220
TI  - Patients failing moderately high doses of omeprazole.

PMID- 9149221
TI  - Dismissing dietary therapy may be premature.

PMID- 9149222
TI  - Bone metabolism in treated celiac children.

PMID- 9149223
TI  - Anti-inflammatory properties of unfractioned heparin in patients with highly
      active ulcerative colitis: a pilot study.

PMID- 9149224
TI  - Extrahepatic cholestasis attributable to tuberculous adenitis.

PMID- 9149225
TI  - No relationship between smoking and hepatitis B virus-related hepatocellular
      carcinoma.

PMID- 9149226
TI  - Metastatic pancreatic carcinoma from the thyroid.

PMID- 9149227
TI  - Two forms of human double-stranded RNA-specific editase 1 (hRED1) generated by
      the insertion of an Alu cassette.
AB  - The double-stranded RNA-specific editase 1 (RED1/ADAR2) is implicated in the
      editing of precursor-mRNAs (pre-mRNA) encoding subunits of glutamate receptors
      (GluRs) in brain. Site-specific deamination of adenosine to inosine alters the
      codon at the Q/R site in GluR-B rendering the heteromeric receptor impermeable to
      Ca2+ ions. We cloned human RED1 (hRED1/hADAR2) cDNAs from a brain cDNA library.
      The human enzyme is 95% identical to the rat homologue. We characterized two
      alternatively spliced forms that differed by the presence of an Alu-J cassette in
      the deaminase domain. For the long form containing the Alu cassette, we isolated
      cDNA clones with an alternative C-terminus and 3'-UTR. An 8.8-kb transcript of
      hRED1 is most abundant in brain and heart, and lower levels are detected in other
      tissues. In vitro editing assays with purified recombinant hRED1 containing or
      lacking the Alu-J cassette revealed that both forms of the protein have the same
      substrate specificity, but differ in their catalytic activity.

PMID- 9149228
TI  - The path of mRNA through the bacterial ribosome: a site-directed crosslinking
      study using new photoreactive derivatives of guanosine and uridine.
AB  - Two new photoreactive nucleotide derivatives have been applied in site-directed
      crosslinking studies with mRNA analogues. 6-Thioguanosine triphosphate or 5
      methyleneaminouridine triphosphate was incorporated into mRNA analogues by T7
      transcription; after transcription, the 5-methyleneaminouridine residues were
      converted to a diazirine derivative. mRNA analogues carrying either 6
      thioguanosine or the diazirine derivative were bound to Escherichia coli
      ribosomes in the presence of tRNA(f)(Met), and photo-crosslinking was induced by
      irradiation at 350 nm. With 6-thioguanosine, specific crosslinks were observed
      from downstream positions +8 or +9 of the mRNA to nt 1196 in helix 34 of the 16S
      rRNA, and from position +12 to nt 530 in helix 18. With the diazirine derivative,
      a crosslink from position +2 (within the AUG codon) to nt 926 in helix 28 was
      found. Taken together with previous data obtained from downstream sites in mRNA
      analogues carrying 4-thiouridine residues, specific crosslinks have now been
      identified from downstream mRNA positions +2, +4, +6, +7, +8, +9, +11, and +12.
      The data confirm that the three 16S rRNA regions involved-helices 18, 28, and 34
      are in the direct neighborhood of the decoding area of the 30S subunit.

PMID- 9149229
TI  - Variable regions V13 and V3 of Saccharomyces cerevisiae contain structural
      features essential for normal biogenesis and stability of 5.8S and 25S rRNA.
AB  - The homologous ribosomal RNA species of all organisms can be folded into a common
      "core" secondary structure. In addition, eukaryotic rRNAs contain a large number
      of segments, located at fixed positions, that are highly variable in size and
      sequence from one organism to another. We have investigated the role of the two
      largest of these variable regions in Saccharomyces cerevisiae 25S rRNA, V13, and
      V3, by mutational analysis in a yeast strain that can be rendered completely
      dependent on the synthesis of mutant (pre-)rRNA. We found that approximately half
      of variable region V13 can be deleted without any phenotypic effect. The
      remaining portion, however, contains multiple structural features whose
      disturbance causes serious growth defects or lethality. Accumulation of 25S rRNA
      is strongly reduced by these mutations, at least in part because they inhibit
      processing of ITS2. Removal of even a relatively small portion of V3 also
      strongly reduces the cellular growth rate and larger deletions are lethal.
      Interestingly, some of the deletions in V3 cause accumulation of 27S(A) pre-rRNA
      and, moreover, appear to interfere with the close coupling between the processing
      cleavages at sites A3 and B1(S). These results demonstrate that both variable
      regions play an important role in 60S subunit formation.

PMID- 9149230
TI  - Importance of structural features for tRNA(Met) identity.
AB  - We showed previously that the tRNA tertiary structure makes an important
      contribution to the identity of yeast tRNA(Met) (Senger B, Aphasizhev R, Walter
      P, Fasiolo F, 1995, J Mol Biol 249:45-58). To learn more about the role played by
      the tRNA framework, we analyzed the effect of some phosphodiester cleavages and
      2'OH groups in tRNA binding and aminoacylation. The tRNA is inactivated provided
      the break occurs in the central core region responsible for the tertiary fold or
      in the anticodon stem/loop region. We also show that, for tRNA(Met) to bind, the
      anticodon loop, but not the anticodon stem, requires a ribosephosphate backbone.
      A tertiary mutant of yeast tRNA(Met) involving interactions from the D- and T
      loop unique to the initiator species fails to be aminoacylated, but still binds
      to yeast methionyl-tRNA synthetase. In the presence of 10 mM MgCl2, the mutant
      transcript has a 3D fold significantly stabilized by about 30 degrees C over a
      wild-type transcript as deduced from the measure of their T(m) values. The k(cat)
      defect of the tRNA(Met) mutant may arise from a failure to overcome an increase
      of the free energetic cost of distorting the more stable tRNA structure and/or a
      tRNA based MetRS conformational change required for formation of transition state
      of aminoacylation.

PMID- 9149231
TI  - Visualizing nuclear export of different classes of RNA by electron microscopy.
AB  - Export of RNA from the cell nucleus to the cytoplasm occurs through nuclear pore
      complexes (NPCs). To examine nuclear export of RNA, we have gold-labeled
      different types of RNA (i.e., mRNA, tRNA, U snRNAs), and followed their export by
      electron microscopy (EM) after their microinjection into Xenopus oocyte nuclei.
      By changing the polarity of the negatively charged colloidal gold, complexes with
      mRNA, tRNA, and U1 snRNA can be formed efficiently, and gold-tagged RNAs are
      exported to the cytoplasm with kinetics and specific saturation behavior similar
      to that of unlabeled RNAs. U6 snRNA conjugates, in contrast, remain in the
      nucleus, as does naked U6 snRNA. During export, RNA-gold was found distributed
      along the central axis of the NPC, within the nuclear basket, or accumulated at
      the nuclear and cytoplasmic periphery of the central gated channel, but not
      associated with the cytoplasmic fibrils. In an attempt to identify the initial
      NPC docking site(s) for RNA, we have explored various conditions that either
      yield docking of import ligands to the NPC or inhibit the export of nuclear RNAs.
      Surprisingly, we failed to observe docking of RNA destined for export at the
      nuclear periphery of the NPC under any of these conditions. Instead, each
      condition in which export of any of the RNA-gold conjugates was inhibited caused
      accumulation of gold particles scattered uniformly throughout the nucleoplasm.
      These results point to the existence of steps in export involving mobilization of
      the export substrate from the nucleoplasm to the NPC.

PMID- 9149232
TI  - The human U6 snRNA intramolecular helix: structural constraints and lack of
      sequence specificity.
AB  - Splicing of mRNA precursors occurs in a massive structure known as the
      spliceosome and requires the function of several small nuclear RNAs (snRNAs). A
      number of studies have suggested potentially important roles for two snRNAs, U2
      and U6, in splicing catalysis. These two RNAs interact extensively with each
      other, as well as with the pre-mRNA, and possible similarities with catalytic
      RNAs have been noted. An important feature of the U2-U6 complex is an
      intramolecular helix in U6, which forms in conjunction with activation of the
      spliceosome. Here we describe a detailed genetic analysis of residues that make
      up this helix in human U6 snRNA, using an in vivo assay in which splicing of a
      test pre-mRNA is dependent on exogenous U6 snRNA. Our results show that many, but
      not all, positions tested are sensitive to mutation. Unexpectedly, base pairing
      is fully compatible with function at all positions, and at many is both necessary
      and sufficient. For example, conversion of two noncanonical A-C pairs to G-C
      pairs did not affect splicing, nor did conversion of an A-G to C-G. Extension of
      the helix by a base pair was also tolerated, provided that base pairing was
      maintained. Most notable was the behavior of a bulged U (U74), which has been
      suggested previously to be of particular importance. Although U74 was sensitive
      to substitution or deletion, incorporation into the helix by insertion of an A
      across from it was without effect, even in the context of a second helix
      stabilizing mutation. We discuss these results in terms of possible mechanisms by
      which U6 snRNA might function in splicing catalysis.

PMID- 9149233
TI  - YRA1, an essential Saccharomyces cerevisiae gene, encodes a novel nuclear protein
      with RNA annealing activity.
AB  - The complexity of eukaryotic mRNA processing suggests a need for certain factors,
      called RNA chaperones, that can modulate RNA secondary structure as well as the
      interactions between pre-mRNA and trans-acting components. To identify factors
      that may fulfill this role in the yeast Saccharomyces cerevisiae, we fractionated
      whole-cell extracts and assayed for activity that could facilitate a specific RNA
      RNA annealing reaction. We detected one strong RNA annealing activity and
      purified it to homogeneity. This previously undescribed factor, Yra1p, is
      localized to the nucleus; its sequence contains one RNP-motif RNA-binding domain.
      The YRA1 gene contains a 766-nt intron, the second-largest identified in this
      organism, and Yra1p serves an essential, nonredundant function. Taken together,
      our findings indicate that Yra1p is likely to have an important role in S.
      cerevisiae nuclear pre-mRNA metabolism.

PMID- 9149234
TI  - Secondary structure of the nascent 7S L RNA mediates efficient transcription by
      RNA polymerase III.
AB  - A structural motif at the 5' end of human 7S L (srp) RNA that is recognized
      specifically by cellular proteins has been identified as an efficient activator
      of RNA polymerase (pol) III transcription in vivo and in vitro. Mutations
      affecting three double-stranded regions or a tetranucleotide bulge of this RNA
      motif result in strongly reduced expression rates. However, effective suppression
      is achieved by compensatory mutations restoring RNA sequence complementarity.
      This activation of transcription is also observed in the context of another pol
      III promoter and is position-dependent. The effects observed are reminiscent of
      the Tat-TAR trans-activation of the human immunodeficiency virus and attribute a
      novel function to the structure of cellular small stable RNA.

PMID- 9149235
TI  - Schistosoma mansoni: gene structure and localization of a homologue to cysteine
      protease ER 60.
AB  - We have isolated and characterized a cDNA encoding the complete sequence of a
      homologue of the ER luminal cysteine protease ER 60 in Schistosoma mansoni. The
      deduced protein of 484 amino acids contains two thioredoxin domains, each with
      the CGHC motif, that characterize all members of the protein disulfide isomerase
      family. The corresponding gene exists as a single copy and consists of six exons,
      interrupted by five very small introns of 32 to 40 nucleotides. Immunohistology
      and in situ hybridization identify the sustentacular cells of the testes, the
      wall cells of the protonephridia, and the gastrodermis of the gut to be the major
      tissues of ER 60 gene expression.

PMID- 9149236
TI  - Plasmodium falciparum-infected erythrocytes adhere to the proteoglycan
      thrombomodulin in static and flow-based systems.
AB  - Plasmodium falciparum-infected erythrocytes can bind to the glycosaminoglycan
      chondroitin sulfate A. In this paper, we demonstrate that thrombomodulin, a
      proteoglycan present on endothelial cells and placental syncytiotrophoblasts,
      supports binding of selected lines of P. falciparum-infected erythrocytes in both
      static and flow-based assays, and that adhesion is dependent on the presence of
      the chondroitin sulfate A chain of thrombomodulin. Chondroitinase treatment of
      thrombomodulin abolished binding, and free chondroitin sulfate A prevented it,
      whereas other soluble glycosaminoglycans had little or no effect. Soluble
      thrombomodulin (with, but not without, its chondroitin sulfate chain) inhibited
      binding at 40 micrograms/ml, but not at physiological concentrations. Parasitized
      erythrocytes bound to cells expressing thrombomodulin, including human umbilical
      vein endothelial cells and A549 cells, and binding was inhibited by free
      chondroitin sulfate A. Established binding to A549 cells or to immobilized
      thrombomodulin was substantially reversed by chondroitin sulfate A at 10
      micrograms/ml. The chondroitin sulfate chain of thrombomodulin is a receptor for
      malaria-infected erythrocytes in static assays and under physiological flow.

PMID- 9149237
TI  - Giardia intestinalis: volume recovery in response to cell swelling.
AB  - The trophozoite from of the protozoan parasite Giardia intestinalis is subjected
      to a changing osmotic environment in the small intestine of the host, and
      consequently effective osmoregulation and control of cell volume are essential to
      its survival. As a first step toward investigating the mechanism by which
      hypoosmotically-activated transport is controlled in this organism, we used a
      light scattering technique to monitor continuously changes in cell volume after
      osmotic challenge. There was a hyperbolic relationship between A550 and giardial
      protein concentration, resulting in linear double reciprocal plots and allowing
      the calculation of relative Giardia cell volumes from A550 values. The initial
      rate of cell swelling was directly proportional to the hypoosmotic gradient when
      the hypoosmotic difference was greater than 50 mOsm kg-1. However, a hypoosmotic
      challenge of < 30 mOsm kg-1 had little effect on cell swelling, suggesting that
      giardial cell rigidity can resist small changes in medium osmolarity. The use of
      light scattering as a measure of giardial cell volume changes was validated using
      a rapidly penetrating solute, ethylene glycol, to induce isoosmotic cell
      swelling. We have previously shown that trophozoites swelled initially when
      subjected to a hypoosmotic challenge and that a subsequent regulatory volume
      decrease was accompanied by rapid alanine efflux and activation of the uptake of
      an alanine analog, 2-aminoisobutyrate. The ethylene glycol-induced isoosmotic
      cell swelling was also followed by a regulatory volume decrease, accompanied by a
      similar rapid release of intracellular alanine and activation of 2
      aminoisobutyric acid uptake. This suggests that an increase in cell volume is the
      primary stimulus for the rapid alanine efflux after hypoosmotic challenge.

PMID- 9149238
TI  - Schistosoma mansoni: maturation rate and drug susceptibility of different
      geographic isolates.
AB  - The fecundities and drug susceptibilities of Schistosoma mansoni isolates from
      Senegal, Puerto Rico, and Kenya have been examined in mice. The Senegal parasite,
      obtained from the field in 1993, was shown to have a longer prepatent period
      (eggs first recovered in the faeces on Day 46 after infection) than those of two
      isolates, from Puerto Rico and Kenya, that had been maintained for a long period
      in the laboratory (faecal eggs recovered on Days 38 and 36 after infection,
      respectively). A Kenyan isolate, also collected from the field in 1994, was shown
      to mature more slowly than the laboratory-maintained Kenyan isolate. Tissue egg
      counts confirmed that early in infection the fecundity of the recently collected
      isolates from Senegal and Kenya was significantly lower than that of the long
      term laboratory-maintained Kenyan isolate. Praziquantel and oxamniquine treatment
      of 8-week-old infections caused a significant (P < 0.001) reduction in worm
      burden in all isolates tested. However, the reduction in worm burden after
      praziquantel treatment of infections of the Senegal isolate (50% reduction) was
      significantly lower than the > 90% reductions in worm burdens after praziquantel
      treatment of mice infected with either of the Kenyan isolates (P < 0.001). The
      study confirms that despite being tolerant to praziquantel, the Senegal isolate
      is fully susceptible to oxamniquine. The praziquantel tolerance of the Senegal
      parasite is not solely attributed to the state of maturation of the parasite at
      the time of drug administration.

PMID- 9149239
TI  - Trypanosoma cruzi in the opossum Didelphis marsupialis: a study of the
      correlations and kinetics of the systemic and scent gland infections in naturally
      and experimentally infected animals.
AB  - The genus Didelphis (Marsupialia, Didelphidae) has the unique capacity of
      supporting both multiplication cycles of Trypanosoma cruzi simultaneously;
      besides the intracellular forms, the epimastigotes can be found multiplying and
      differentiating abundantly in the lumen of the scent glands. The biological
      significance of the life cycle of T. cruzi within the scent glands of Didelphis
      marsupialis, as well as its contribution to the epidemiology of the disease, is
      presently unclear. In order to clarify the mechanisms involved in the
      colonization of this singular habitat by T. cruzi, as well as to understand its
      biological role, we have carried out a serological and parasitological follow-up
      of both natural and experimental infections of young and adult opossums. Although
      all natural infections were stable and long lasting, no infected scent glands
      were found, indicating that the stability of the systemic infections does not
      depend on the presence of flagellates in the scent gland. In 84% of the
      experimentally infected animals the colonization of the scent glands was preceded
      by a period of patent parasitemia. Parasitism of the scent glands was essentially
      permanent and bilateral, and its maintenance was independent of circulating
      parasites. Moreover, the course of the infection differed depending on the source
      (scent glands versus axenic culture-derived) of the metacyclic forms. Our results
      suggest that parasitism of the SG of D. marsupialis is most likely a secondary
      acquisition, a step toward independence from the insect vector, similarly to what
      is accepted for Trypanosoma equiperdum.

PMID- 9149240
TI  - Plasmodium falciparum: allelic variation in the merozoite surface protein 1 gene
      in wild isolates from southern Vietnam.
AB  - Allelic variation in the Plasmodium falciparum merozoite surface protein 1 (MSP1)
      gene is expressed as an association of allelic types in variable blocks. In this
      study, a PCR strategy that can detect 24 different MSP1 association types was
      used to investigate allelic variation in the MSP1 gene. We identified 236
      distinct association type clones in 136 wild isolates collected from southern
      Vietnam, analysis of which revealed that (1) recombination between two
      representative allelic types in the central part of the MSP1 gene did not exist,
      (2) frequency distribution of MSP1 association types did not differ in different
      population groups, and (3) particular MSP1 association types were predominant.
      Statistical analysis for the association of allelic types indicated significant,
      nonrandom associations between blocks 4 and 6 but not between blocks 2 and 4, and
      2 and 6. These results suggest that selection operates in favor of particular
      MSP1 association types. In addition, direct sequencing of 31 isolates confirmed
      reported sequence substitutions in the C-terminal 19-kDa Cys-rich region of MSP1,
      supporting a notion of limited variations in this region, a strong vaccine
      candidate molecule.

PMID- 9149241
TI  - Leishmania spp.: nitric oxide-mediated metabolic inhibition of promastigote and
      axenically grown amastigote forms.
AB  - The antimicrobial effect of activated macrophages on parasites involves nitric
      oxide (NO). NO induces intracellular parasite killing in murine leishmaniasis.
      Nevertheless, the mechanisms of action of NO as a final effector molecule on
      intracellular forms of Leishmania are unknown. The recent development of
      axenically grown amastigote forms of different Leishmania species allowed direct
      investigation of NO activity on active and dividing populations of the mammalian
      stage of various Leishmania species, which normally are only found
      intracellularly. Authentic NO gas, which reproduced the antimicrobial effect
      elaborated by activated macrophages, was flushed on promastigote and axenically
      cultured amastigote forms of L. mexicana, L. amazonensis, and L. chagasi
      suspended in degassed phosphate-buffered saline (PBS). After NO treatment, the
      viability of parasites gradually decreased as a function of time postflushing
      when compared to controls. Interestingly NO killing was more effective on
      promastigote forms than on amastigote forms. After 12-hr postflushing incubation
      in PBS, cultures of NO-treated parasites, contrary to controls (N2-treated),
      failed to proliferate whatever the species and the developmental stage
      considered. Addition of both FeSO4 and L-cysteine to PBS immediately after NO
      treatment reversed the capacity of authentic NO gas to inhibit the multiplication
      of both parasite stages of Leishmania. Supplementation of PBS with alpha
      ketoglutarate and cis-aconitate (citric acid cycle substrates) also reversed the
      leishmanicidal activity of NO, whereas addition of citrate was less effective.
      The course of the developmental life cycle in vitro was also inhibited by NO gas
      treatment. Enzymatic analysis showed that aconitase activity was dramatically
      reduced by NO gas, whereas glucose phosphate isomerase, aspartate transferase,
      and phosphoglucomutase activities were unchanged. In accordance, promastigote and
      amastigote forms of Leishmania were shown to be killed by antimycin A, an
      inhibitor of mitrochondrial respiration. All these data demonstrated that NO
      action led to lethal metabolic inhibition in both developmental parasite stages
      by, at least in part, triggering iron loss from enzyme(s) with iron-sulfur
      prosthetic groups, in particular aconitase.

PMID- 9149242
TI  - Schistosoma mansoni: the developmental regulation and immunolocalization of
      antioxidant enzymes.
AB  - Antioxidant enzymes from S. mansoni, cytosolic Cu-Zn superoxide dismutase (CT
      SOD), signal-peptide-containing SOD (SP-SOD), glutathione peroxidase (GPX), and
      glutathione transferase (GST) were compared for their relative levels of
      transcript expression throughout development in a semiquantitative reverse
      transcriptase-polymerase chain reaction assay. All of the antioxidant enzymes
      exhibited a similar pattern of developmental regulation. Adult worms have the
      highest level of specific mRNA compared with larval stages. GST shows the highest
      level of expression, being approximately 10-fold more abundant than CT-SOD and SP
      SOD and 100-fold more abundant than GPX. This order of expression was nearly
      consistent for all the developmental stages studied. To localize the antioxidant
      enzymes, immunofluorescence staining was performed on 3-hr schistosomula and
      adult worms. GPX, SP-SOD, and CT-SOD were all found to be associated with the
      adult tegument and gut epithelium. SP-SOD was also associated with organelle and
      cell membranes of parenchymal cells and interestingly with the spines of adult
      worms. Schistosomula, on the other hand, showed little immunofluorescence. These
      studies further demonstrate the developmental regulation of antioxidant enzymes
      and localize them to the host-parasite interface, supporting the notion that they
      have a role in allowing adult worms to evade immune attack.

PMID- 9149243
TI  - Plasmodium falciparum: a high proportion of parasites from a population of the
      Dd2 strain are able to invade erythrocytes by an alternative pathway.

PMID- 9149244
TI  - Taenia ovis: copy number of genes encoding host-protective antigens determined by
      competitive PCR.

PMID- 9149245
TI  - Haemonchus contortus: inter- and intrageographic isolate heterogeneity of
      proteases in adult worm excretory-secretory products.

PMID- 9149246
TI  - Intraoperative diagnostic and interventional magnetic resonance imaging in
      neurosurgery.
AB  - OBJECTIVE: The benefits of intraoperative magnetic resonance (MR) imaging for
      diagnostic and therapeutic measures are as follows: 1) intraoperative update of
      data sets for navigational systems, 2) intraoperative resection control of brain
      tumors, and 3) frameless and frame-based on-line MR-guided interventions. The
      concept of an intraoperative MR scanner in the sterile environment of operating
      theater is presented, and its advantages, disadvantages, and limitations are
      discussed. METHODS: A 0.2-tesla magnet (Magnetom Open; Siemens AG, Erlangen,
      Germany) inside a radiofrequency cabin with a radiofrequency-shielded sliding
      door was installed adjacent to one of the operating theaters. A specially
      designed patient transport system carried the patient in a fixed position on an
      air cushion to the scanner and back to the surgeon. RESULTS: In a series of 27
      patients, intraoperative resection control was performed in 13 cases, with
      intraoperative reregistration in 4 cases. Biopsies, cyst aspirations, and
      catheter placements (mainly frameless) were performed under direct MR
      visualization with fast image sequences. The MR-compatible equipment and the
      patient transport system are safe and reliable. CONCLUSION: Intraoperative MR
      imaging is a safe and successful tool for surgical resection control and is
      clearly superior to computed tomography. Intraoperative acquisition of data sets
      eliminates the problem of brain shift in conventional navigational systems.
      Finally, on-line MR-guided interventional procedures can be performed easily with
      this setting. As with all MR systems, individual testing with phantoms,
      application of correction programs, and determination of the optimal amount of
      contrast media are absolute prerequisites to guarantee patient safety and
      surgical success.

PMID- 9149247
TI  - Elastin degradation in the superficial temporal arteries of patients with
      intracranial aneurysms reflects changes in plasma elastase.
AB  - OBJECTIVE: alpha 1-Antitrypsin (AAT) and alpha 2-macroglobulin (AMG) are elastase
      inhibitors that bind the enzyme and reduce measured levels of free elastase. It
      was recently demonstrated that some patients with intracranial aneurysms have
      significantly elevated plasma elastase (PE) levels. Although this elevation is
      unrelated to plasma AAT, it is unknown whether abnormal AAT phenotypes or reduced
      AMG levels play a role. Moreover, the pathological significance of this elevation
      is not understood. METHODS: Plasma from 24 patients with aneurysms (ruptured, n =
      15; unruptured, n = 9) and 10 age-matched patients who comprised a control group
      was analyzed for PE and AMG levels by enzyme-linked immunosorbent assay and for
      AAT phenotype by isoelectric focusing. Sections of superficial temporal temporal
      artery obtained from these patients at the time of surgery were examined for
      evidence of elastin degradation by using a van Gieson stain, with scoring on a
      nine-point quantitative scale. RESULTS: Patients with aneurysms showed
      significantly elevated PE levels (119 +/- 28 versus 17 +/- 7 micrograms/ml, P <
      0.05), but AMG levels were not decreased. AAT phenotypic abnormalities were
      observed in 10% (2 of 20) of the patients with aneurysms, but this was not
      different from the expected population incidence (7%). Elastin degradation scores
      were significantly higher in patients with aneurysms than in patients control
      group (4.26 +/- 0.54 versus 1.21 +/- 0.43, P < 0.05). In addition, patients with
      higher elastase levels (> 80 micrograms/ml) demonstrated 55% higher degradation
      scores than did those with lower elastase levels (< 80 micrograms/ml).
      CONCLUSION: These data suggest that high PE levels may play a role in systemic
      arterial elastin degradation seen in patients with intracranial aneurysms. These
      data also support the contention that elevated elastase levels are not the result
      of decreased protease inhibitor levels. Although PE levels were significantly
      higher for the entire group of patients with aneurysms, this assay has relatively
      low sensitivity for predicting the presence of unruptured aneurysms. Additional
      study is necessary to determine whether serum elastase levels greater than 80
      micrograms/ml, in the setting of other risk factors, are useful in identifying
      asymptomatic patients for additional screening.

PMID- 9149248
TI  - Effects of iodine-125 brachytherapy on the proliferative capacity and
      histopathological features of glioblastoma recurring after initial therapy.
AB  - OBJECTIVE: To determine the effect of initial therapy (surgery and external beam
      radiation) on the proliferative capacity of glioblastoma and whether adjunctive
      high focused doses of radiation therapy can further reduce the proliferative
      capacity of the tumor. This would provide a rationale for attempting to further
      control local tumor growth with the different forms of high-dose focused
      radiation available. METHODS: Patients with glioblastoma were initially treated
      within a randomized, controlled study with or without iodine-125 (125 I)
      brachytherapy after initial surgical resection and external beam radiation (50 Gy
      in 25 fractions). Specimens from 24 consecutive patients later reoperated for
      "recurrence" were used to determine the effects of 125 I brachytherapy on the
      histological features and proliferating cell nuclear antigen index of the tumor
      tissue. RESULTS: 125 I brachytherapy reduced histological features prognostic for
      tumor progression, i.e., cellularity, pleomorphism, vessel hyperplasia, and
      degree of mitosis (P < 0.05). The degree of mitosis (marker for the mitotic or
      "M" phase) and proliferating cell nuclear antigen index (market for the late G1
      and S phase) provide complementary data on the cell kinetics of the tumor.
      Proliferating cell nuclear antigen immunostaining was lower in the 125 I
      brachytherapy group (34.6 +/- 8.2%, mean +/- standard error) compared with the
      control nonimplant group (68.2 +/- 3.5%). 125 I brachytherapy produced a dramatic
      reduction in mitotic figures (mean histological score = 0.0 +/- 0.0). CONCLUSION:
      Adjunctive treatment of glioblastoma with discrete high doses of radiation
      therapy delivered by 125 I brachytherapy allows further control of the
      proliferative capacity of the tumor.

PMID- 9149249
TI  - Management of vestibular schwannomas (acoustic neuromas): the value of
      neurophysiology for evaluation and prediction of auditory function in 420 cases.
AB  - OBJECTIVE: From 1978 to 1993, 1000 vestibular schwannomas were operated on at the
      Department of Neurosurgery at Nordstadt Hospital. The goal was to improve the
      chances of hearing preservation by recording auditory brain stem responses
      (ABRs). ABRs can be used for preoperative classification of cochlear nerve
      impairment and for prediction of the chances of hearing preservation. PATIENTS
      AND METHODS: In addition to the previously described audiometric testing, the
      patients underwent perioperative and intraoperative bilateral ABR recording at
      100-dB condensation and rarefaction click stimulation. The classification system
      of five types of ABRs, as presented before, is based on the presence and on the
      latencies of Waves I, III, and V, with a special emphasis on Wave III's
      representing the activity of the first brain stem nuclei within the auditory
      pathway. According to an analysis of 420 preoperative ABRs, in case of a
      preoperative Type 1 or 2, the rate of hearing preservation is 80%. DISCUSSION: In
      the case of good clinical and audiometric hearing, a severely deteriorated ABR is
      mostly an indicator of severe nerve compression and adhesion by the tumor. In
      view of subsequently reported experiences with intraoperative ABR monitoring, the
      value of the presented system emphasizing the importance of Wave III is stressed
      and discussed with other views in the literature. The criteria presented here are
      not designed for recognition of retrocochlear disease but aim for evaluation of
      the state of the auditory nerve and its perspective. CONCLUSION: By the presented
      classification of ABR Type B1 through B5, preoperative prediction of the
      likelihood of hearing preservation is improved.

PMID- 9149250
TI  - A new ventriculoperitoneal shunt with a telemetric intracranial pressure sensor:
      clinical experience in 94 patients with hydrocephalus.
AB  - OBJECTIVE: We have developed a telemetric intracranial pressure sensor (OSAKA
      telesensor; Nagano Keiki Seisakusyo Co. Ltd., Tokyo, Japan) and investigated the
      clinical usefulness of new ventriculoperitoneal shunting with an OSAKA
      telesensor, an on-off valve, and a programmable valve. METHODS: The OSAKA
      telesensor was applied in 94 patients at Osaka Medical College between March 1986
      and December 1995. Postoperative management, postoperative course, postural
      change of intracranial pressure (ICP), and zero drift of the OSAKA telesensor
      were investigated. RESULTS: ICP was measured easily in all patients with no
      inconvenience. The setting of the programmable valve was adjusted postoperatively
      38 times in 25 patients. Postoperative ICP in the upright position was -14.9 +/-
      4.5 mm Hg, and the difference in ICP between the supine and the upright position
      was about 20 mm Hg. The slope of the decrease in ICP with continuous postural
      changes from the supine to the upright position was steep until about 30 to 45
      degrees but became incrementally less or even rose slightly about this angle. The
      initial slope was steeper when the shunt was open than when the shunt was closed;
      it was also steeper postoperatively than preoperatively. This initial slope,
      therefore, may indicate the intracranial compliance. Seven cases of shunt
      malfunction were diagnosed correctly by ICP measurements. Zero drift of the OSAKA
      telesensor was easily corrected by comparing the ICP reading from the telesensor
      with the puncture pressure in the on-off valve. CONCLUSION: The OSAKA telesensor
      is very useful in the postoperative care and pathophysiological evaluation of
      patients with hydrocephalus.

PMID- 9149251
TI  - Magnetoencephalographic mapping: basic of a new functional risk profile in the
      selection of patients with cortical brain lesions.
AB  - OBJECTIVE: Surgical management of cortical lesions adjacent to or within the
      eloquent cerebral cortex requires a critical risk: benefit analysis of the
      procedure before intervention. This study introduced a measure of surgical risk,
      based on preoperative magnetoencephalographic (MEG) sensory and motor mapping,
      and tested its value in predicting surgical morbidity. METHODS: Forty patients
      (21 men and 19 women; mean age, 36.5 yr) with cortical lesions (12 arteriovenous
      malformations and 28 tumors) in the vicinity of the sensorimotor cortex were
      classified into high-, medium-, or low-risk categories by using the MEG-defined
      functional risk profile (FRP). This was based on the minimal distance between the
      lesion margin and the sensory and motor MEG sources, superimposed on a magnetic
      resonance imaging scan. Case management decisions were based on the MEG mapping
      derived FRP in combination with biopsy pathological findings, radiographic
      findings, and anatomic characteristics of the lesion. A recently developed
      protocol was used to transform MEG source locations into the stereotactic
      coordinate system. This procedure provided intraoperative access to MEG data in
      combination with stereotactic anatomic data displays routinely available on-line
      during surgery. RESULTS: It was determined that 11 patients diagnosed as having
      gliomas had high FRPs. The margin of the lesion was less than 4 mm from the
      nearest MEG dipole or involved the central sulcus directly. A nonoperative
      approach was used for six patients of this group, based on the MEG mapping
      derived FRP. In the group with arteriovenous malformations, 6 of 12 patients with
      high or medium FRPs underwent nonoperative therapy. The remaining 28 patients,
      whose lesions showed satisfactory FRPs, underwent uneventful lesion resection,
      without postoperative neurological deficits. CONCLUSION: Our results suggest that
      MEG mapping-derived FRPs can serve as powerful tools for use in presurgical
      planning and during surgery.

PMID- 9149252
TI  - Endoscopic transseptal transsphenoidal surgery for pituitary tumors.
AB  - OBJECTIVE: Transseptal transsphenoidal surgery of pituitary tumors is a well
      established surgical technique. The sublabial approach and the open rhinoplasty
      approach are most commonly used. In both cases, the surgical avenue is along the
      entire length of the nasal septum, removing both nasal cartilage and the vomer.
      Septal perforations and upper dental anesthesia are frequent complications of the
      standard approaches. We describe our initial experience in using the nasal
      endoscope for the first stage of the operation. METHODS: A nasal endoscope was
      used to open the anterior wall of the sphenoid sinus. Our initial incision was in
      the posterior third of the septum, removing only the vomer. After the sphenoid
      sinus was opened, we inserted a speculum and proceeded with the operation with an
      operating microscope. After the speculum was in place, it was easier to proceed
      with the microscope, which allows binocular vision and bimanual operation.
      RESULTS: The procedure was used for our most recent 14 consecutive patients with
      pituitary adenomas. No complications related to the approach were encountered for
      any of the patients in follow-up monitoring. CONCLUSION: The endoscopic
      transseptal approach to the sphenoid sinus for pituitary surgery was found to be
      easy, time-saving, and without septal or sublabial complications.

PMID- 9149253
TI  - Preliminary results on the management of unruptured intracranial aneurysms with
      magnetic resonance angiography and computed tomographic angiography.
AB  - OBJECTIVE: The goal was to assess the capability of magnetic resonance
      angiography (MRA) and computed tomographic angiography (CTA) to replace catheter
      angiography in the evaluation of unruptured intracranial aneurysms. METHODS: A
      prospective evaluation of a 1-year period included all patients suspected of
      harboring unruptured intracranial aneurysms at a single institution. All patients
      underwent magnetic resonance imaging, MRA, and CTA, for comparison with
      intraoperative findings or results from catheter angiography. Both MRA and CTA
      now provide submillimeter resolution of vascular structures, with accurate
      detection of intracranial aneurysms of a diameter greater than or equal to 3 mm.
      This resolution calls into question the universal need for catheter angiography
      in the care of patients with suspected intracranial aneurysms. When the catheter
      angiography can be avoided, radiological costs can be reduced by as much as two
      thirds while eliminating the risk of arterial injury and stroke. RESULTS:
      Excellent visualization of the intracranial vasculature was provided by both MRA
      and CTA. No vascular lesion was detected at surgery or by formal angiography that
      was not visualized by noninvasive angiographic techniques. The three-dimensional
      anatomy of the aneurysm complex (unavailable with catheter angiography) was well
      depicted by both MRA and CTA. CTA was unique in its capacity to display the
      relationship of vascular structures to bone, information that is invaluable for
      planning operative strategies for lesions such as carotidophthalmic artery
      aneurysms. Additionally, acquisition of CTA images was very rapid, with a
      scanning time of less than 1 minute. Both MRA and CTA allowed for retrospective
      manipulation of data into an infinite number of views, including views that
      paralleled those encountered through the operative microscope. Additionally, both
      MRA and CTA can depict the internal anatomy of aneurysms, an ability not
      possessed by intra-arterial angiography. This ability alerts the surgeon to
      possible intraoperative risks, such as plaque in the lumen of an aneurysm or
      calcium within the walls of the arteries. CONCLUSION: Both MRA and CTA provide
      several advantages over digital subtraction angiography, in addition to reduced
      costs and avoidance of arterial injury and stroke. These include retrospective
      manipulation of data in a 360-degree format, visualization of the internal
      anatomy of arteries and aneurysms, three-dimensional depiction of anatomy, and
      rapid data acquisition. Preliminary data and a review of the literature suggest
      that MRA, when used in concert with CTA, can replace catheter angiography in the
      assessment of select patients harboring unruptured intracranial aneurysms.
      Although no firm conclusions or generalizations can be drawn from this small
      cohort of patients, it is hoped that this report will stimulate interest and
      further study at other institutions.

PMID- 9149254
TI  - Frameless stereotactic guidance for surgery of the upper cervical spine.
AB  - OBJECTIVE: The goal was to evaluate and describe the use of a frameless, computed
      tomography-guided, stereotactic technique in complex procedures involving the
      craniocervical junction. METHODS: Eleven procedures, including transoral odontoid
      resection, posterior atlantoaxial fusion with transarticular C1-C2 screw
      fixation, and spinal tumor resection, were performed in the preceding 26 months.
      In each case, frameless stereotaxy was used to plan the incision, to define
      resection margins, and to determine the appropriate orientation of
      instrumentation. RESULTS: There were no intraoperative complications noted. Each
      patient underwent adequate resection of the pathological lesion and satisfactory
      placement of instrumentation. The stereotactic system provided detailed anatomic
      visualization, which increased the confidence of the surgeon during the
      procedure. The system limited the need for extensive surgical exposure, reduced
      fluoroscopy time, and decreased the risk of neurovascular injury. CONCLUSION:
      Frameless stereotaxy provided the surgeon with intraoperative information
      regarding the extent of bone and soft tissue resection. It provided a
      multidimensional view of anatomic relationships in the operative field, which
      significantly increased surgical accuracy and safety.

PMID- 9149255
TI  - Intraoperative microvascular Doppler sonography in aneurysm surgery.
AB  - OBJECTIVE: The goal was to evaluate the efficacy and reliability of
      intraoperative microvascular doppler sonography for the assessment of cerebral
      hemodynamics in aneurysm surgery. METHODS: For 35 patients who underwent surgery
      for the treatment of 42 intracranial aneurysms, microvascular doppler sonography
      with a 20-MHz probe (1-mm diameter) was used before and after clip application,
      to confirm the obliteration of aneurysms. Assessment of the patency of the parent
      vessels and all branching arteries was performed. The findings from doppler
      sonography were confirmed with either intraoperative angiography or immediate
      postoperative angiography. RESULTS: The 1-mm microprobe was able to insonate all
      vessels of the circle of Willis and their major branches; furthermore,
      perforating arteries were reliably insonated. For 11 patients (31%), doppler
      sonography exposed parent artery or branching artery stenosis or occlusion and
      guided the immediate adjustment of aneurysm clip placement. The findings from
      intraoperative microvascular doppler sonography correlated with findings from
      angiography in all cases. There were no complications of microvascular doppler
      probe use. CONCLUSION: Intraoperative microvascular doppler sonography is a safe,
      instantaneous, effective, reliable, and cost-effective method for documenting the
      patency of parent vessels, arterial branches, and major perforators and the
      complete occlusion of cerebral aneurysms. This technique can be reliably used, in
      many instances, instead of intraoperative angiography for the surgical treatment
      of aneurysms.

PMID- 9149256
TI  - The transcallosal interforniceal approach to the third ventricle: anatomic and
      microsurgical aspects.
AB  - OBJECTIVE: The ability to visualize median-sagittal brain structures by magnetic
      resonance imaging improves planning for surgery to treat lesions of the third
      ventricle. The most appropriate path to the third ventricle is the transcallosal
      approach. The present study was undertaken to describe the surgical anatomy and
      landmarks encountered during this approach. METHODS: The transcallosal
      interforniceal approach was undertaken in 30 formalin-fixed brains using an
      operating microscope. The surface landmarks for the approach pathway were the two
      points, P5 and P7, located 5 and 7 cm anterior to the central sulcus,
      respectively. Using these two points on the cortical surface as references, a
      variety of measurements were made to provide quantitative information about
      distances between brain structures that are encountered during the surgical
      approach. Measurements that were made include the following: 1) the distance
      between P5 and the cingulate sulcus, 2) the distance between the cingulate sulcus
      and the corpus callosum, 3) the height of the corpus callosum, 4) the distance
      between the anterior commissure and the foramen of Monro, and 5) the distance
      between the lower margin of the corpus callosum and the fornix. RESULTS: Mean
      values for these key measurements were as follows: 1) 23.96 mm (range, 15.0-32.0
      mm); 2) 13.50 mm (range, 8.0-20.0 mm) with reference to P5 and 12.73 mm (range,
      16.0-18.0 mm) with reference to P7; 3) 6.12 mm (range, 4.0-8.0 mm) with reference
      to P5 and 6.60 mm (range, 4.0-9.0 mm) with reference to P7; 4) 4.96 mm (range,
      2.5-10.0 mm), independent of P5 and P7; and 5) 8.46 mm (range, 3.0-16.0 mm) with
      reference to P5 and 11.04 mm (range, 6.0-22.0 mm) with reference to P7.
      CONCLUSION: The detailed quantitative information obtained in this study about
      the interforniceal approach permitted definition of surgical approach pathways
      that preserve important anatomic structures, such as the motor strip, genu of the
      corpus callosum, fornical commissure (hippocampal commissure), anterior
      commissure, and fornical columns. The approach through this surgical corridor can
      easily be planned and performed in individual cases using median-sagittal
      magnetic resonance imaging scans.

PMID- 9149258
TI  - Effectiveness of spinal cord stimulation in the management of chronic pain:
      analysis of technical drawbacks and solutions.
AB  - OBJECTIVE: A major drawback of currently available spinal cord stimulation (SCS)
      systems for the management of chronic intractable pain, especially of widespread
      pain patterns as in reflex sympathetic dystrophy, is the generally limited
      paresthesia coverage. The aim of this study is to analyze the origin of this
      problem and to provide solutions. METHODS: Results from theoretical studies, in
      which a computer model was used to mimic the effects of SCS on spinal nerve
      fibers, were used to analyze which factors may limit paresthesia coverage. Model
      predictions were verified by empirical data from clinical literature. RESULTS:
      When using common SCS electrodes, both perception threshold and motor/discomfort
      threshold are generally related to dorsal root stimulation. Because these
      thresholds have a small ratio (approximately 1:1.4), stimulation of dorsal column
      fibers and paresthesia coverage is limited by this small range of stimulation.
      When the distance between the epidural electrode and spinal cord is large
      (midthoracically), the threshold for dorsal column stimulation exceeds discomfort
      threshold, resulting only in segmental paresthesia. The range of dorsal column
      stimulation and paresthesia coverage can be improved when using either an
      optimally dimensioned rostrocaudal bi-/tripole or a transverse tripole ("guarded
      cathode"). When applying the latter in combination with a dual channel pulse
      generator providing simultaneous pulses, paresthesias can simply be changed to
      optimally cover the painful area. CONCLUSION: Paresthesia coverage and pain
      management by SCS can be improved when using electrodes as proposed.

PMID- 9149257
TI  - Outcome, cost analysis, and long-term follow-up in preterm infants with massive
      grade IV germinal matrix hemorrhage and progressive hydrocephalus.
AB  - OBJECTIVE: The benefit of aggressive management and surgical intervention in
      preterm infants with massive Grade IV intracranial hemorrhage has been questioned
      based on the poor outcome of this group of patients despite such therapy. To
      further delineate this problem, we reviewed the records of premature neonates in
      this category as to outcome and initial hospital cost. METHODS: We performed a
      retrospective review of the medical records at our institution from 1977 to 1987
      to identify premature neonates who had sustained massive hemorrhagic infarction
      of one hemisphere in addition to having blood in both ventricles and progressive
      hydrocephalus. RESULTS: During the study, a total of 52 such patients were
      identified, only 19 (6 female and 13 male patients) of whom survived.
      Intellectual function was observed to be greater than 2 standard deviations below
      the mean in 15 of the 19 patients, between 1 and 2 standard deviations below the
      mean in 1 of 19, and 1 standard deviation below the mean in 3 of 19. Motor
      function was as follows: 12 of 19 had marked spastic quadriparesis, 2 of 19 had
      moderate spastic quadriparesis, 3 of 19 had spastic hemiplegia, 1 of 19 had
      spastic diplegia, and 1 of 19 had mild spastic hemiparesis. Eleven of 19 had
      chronic seizure disorders. The first hospitalization cost for the group of
      patients exceeded, on the average, $150,000 per patient for the 19 long-term
      survivors. CONCLUSION: As we have previously reported, logistic regression
      analysis determined that grade of hemorrhage was the only significant predictor
      of cognitive and motor outcomes. Most premature neonates with massive
      intracranial hemorrhages do not survive. The outcomes in those who do is very
      poor and the cost so high that we suggest that until therapeutic intervention
      exhibits efficacy, the consideration of withdrawal of life support should be
      presented as an option to the parents of these unfortunate children.

PMID- 9149259
TI  - Current concepts in neuro-oncology: the cell cycle--a review.
AB  - Uncontrolled cellular proliferation is the hallmark of human malignant brain
      tumors. Their growth proceeds inexorably, in part because their cellular
      constituents have an altered genetic code that enables them to evade the checks
      and balances of the normal cell cycle. Recently, a number of major advances in
      molecular biology have led to the identification of several critical genetic and
      enzymatic pathways that are disturbed in cancer cells resulting in uncontrolled
      cell cycling. We now know that the progression of a cell through the cell cycle
      is controlled in part by a series of protein kinases, the activity of which is
      regulated by a group of proteins called cyclins. Cyclins act in concert with the
      cyclin-dependent kinases (CDKs) to phosphorylate key substrates that facilitate
      the passage of the cell through each phase of the cell cycle. A critical target
      of cyclin-CDK enzymes is the retinoblastoma tumor suppressor protein, and
      phosphorylation of this protein inhibits its ability to restrain activity of a
      family of transcription factors (E2F family), which induce expression of genes
      important for cell proliferation. In addition to the cyclins and CDKS, there is
      an emerging family of CDK inhibitors, which modulate the activity of cyclins and
      CDKs. CDK inhibitors inhibit cyclin-CDK complexes and transduce internal or
      external growth-suppressive signals, which act on the cell cycle machinery.
      Accordingly, all CDK inhibitors are candidate tumor suppressor genes. It is
      becoming clear that a common feature of cancer cells is the abrogation of cell
      cycle checkpoints, either by aberrant expression of positive regulators (for
      example, cyclins and CDKs) or the loss of negative regulators, including p21Cip1
      through loss of function of its transcriptional activator p53, or deletion or
      mutation of p16ink4A (multiple tumor suppressor 1/CDKN2) and the retinoblastoma
      tumor suppressor protein. In this review, we describe in detail our current
      knowledge of the normal cell cycle and how it is disturbed in cancer cells.
      Because there have now been a number of recent studies showing alterations in
      cell cycle gene expression in human brain tumors, we will review the derangements
      in both the positive and negative cell cycle regulators that have been reported
      for these neoplasms. A thorough understanding of the molecular events of the cell
      cycle may lead to new opportunities by which astrocytoma cell proliferation can
      be controlled either pharmacologically or by gene transfer techniques.

PMID- 9149260
TI  - Meningiomas: role of vascular endothelial growth factor/vascular permeability
      factor in angiogenesis and peritumoral edema.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF)/vascular permeability factor
      (VPF) is a potent angiogenic growth factor implicated in the tumor
      angiogenesis/metastasis of a number of human cancers. Activation of receptors for
      VEGF/VPF is specifically mitogenic to endothelial cells and increases their
      permeability. Although extensive literature exists regarding VEGF/VPF in human
      astrocytomas, little is known about its potential biological role(s) in
      meningiomas. Our interest in meningiomas was initiated by the observation that
      some meningiomas are extremely vascular and are occasionally associated with a
      considerable degree of peritumoral brain edema, both potentially related to the
      biological attributes of VEGF/VPF. METHODS: As a first test of this hypothesis,
      we examined a cohort of 18 meningiomas for expression of VEGF/VPF at the
      messenger ribonucleic acid and protein levels and correlated expression with
      pathological characteristics, vascularity, and degree of peritumoral edema.
      RESULTS: The majority of meningiomas expressed VEGF/VPF at both the messenger
      ribonucleic acid and protein levels. Corresponding serial sections were stained
      with an endothelial cell marker to obtain a microvascular density count, which
      positively correlated (P = 0.0005) with expression of VEGF/VPF. Furthermore,
      meningiomas with a large amount of peritumoral edema, as determined from the
      preoperative computed tomographic scans or magnetic resonance imaging scans, had
      elevated expression of VEGF/VPF (P = 0.05). CONCLUSION: These data suggest that
      VEGF/VPF may play a role in both meningioma vascularity and peritumoral edema.

PMID- 9149261
TI  - Effects of basic fibroblast growth factor on in vivo cerebral tumorigenesis in
      rats.
AB  - OBJECTIVE: In vitro evidence suggests that basic fibroblast growth factor (bFGF)
      promotes tumor cell proliferation and angiogenesis. In this study, we evaluated
      the early and delayed effects of recombinant human bFGF on the early and late
      phases of in vivo, in situ tumorigenesis in rats. METHODS: Brain tumors were
      induced by transplacentally exposing fetal rats to N-nitrosoethylurea on Day 17
      of pregnancy. On postnatal (PN) Day 60 or 90, N-nitrosoethylurea-exposed rats
      underwent stereotactic intraventricular implantation of Gelfoam saturated with
      bFGF (60 micrograms) or vehicle; the rats were killed 4 days (early group) or 30
      days (delayed group) later. The early and delayed effects of bFGF on the early
      phase of tumorigenesis (PN Day 60) were evaluated in 14 and 10 rats,
      respectively; early and delayed effects on the late phase of tumorigenesis (PN
      Day 90) were evaluated in 12 rats each. RESULTS: Histological examination 30 days
      after implantation showed a significantly higher tumor rate in rats that had been
      treated with bFGF on PN Day 90, compared with vehicle-treated control rats (P <
      0.05); furthermore, in the bFGF-treated animals there was significantly greater
      intratumoral and periventricular glial fibrillary acidic protein expression, as
      determined immunohistochemically. Increased vascularity in the tumor ipsilateral
      to the implant was found in 2 of 14 rats that had been treated with bFGF on PN
      Day 60. CONCLUSION: These findings support in vitro evidence that bFGF and its
      receptor complex are implicated in the genesis and progression of N
      nitrosoethylurea-induced brain tumors in this animal model.

PMID- 9149262
TI  - Long-term toxicity and neuropathology associated with the sequencing of cranial
      irradiation and enhanced chemotherapy delivery.
AB  - OBJECTIVE: The goal was to evaluate, at 1 year, 75 Long-Evans rats for survival
      rates and toxicity associated with the sequencing of cranial irradiation and
      enhanced chemotherapy delivery. METHODS: Seventy-five Long-Evans rats were
      randomized into four groups and evaluated at 1 year for survival rates and
      toxicity associated with the sequencing of cranial irradiation and enhanced
      chemotherapy delivery. Radiation (2,000 cGy) was administered as a single
      fraction, by using parallel opposed portals, 30 days before chemotherapy (Group
      1), 24 hours before chemotherapy (Group 2), 30 days after chemotherapy (Group 3),
      or without chemotherapy or without radiation (control group, Group 4). Five
      subgroups within each treatment group included rats receiving intra-arterially
      administered methotrexate (1 g/m2) or intravenously administered etoposide (200
      mg/m2) combined with intra-arterially administered carboplatin (200 mg/m2),
      administered with or without osmotic blood-rain barrier disruption, and a group
      receiving normal saline solution after blood-brain barrier disruption. RESULTS:
      There was a significant increase in total toxic effects when the three
      experimental groups were compared with the control group (P = 0.001, 0.006, and
      0.013 for Groups 1, 2, and 3, respectively). All groups receiving radiation and
      chemotherapy (particularly carboplatin and etoposide) had an increased incidence
      of hind limb paralysis, resembling experimental allergic neuritis (P = 0.053).
      Statistical analysis showed a trend toward increased mortality rates in Group 1
      (antecedent radiation), compared with the control group (P = 0.082), and an
      increased incidence of intracerebral calcification (P = 0.019). No differences in
      mortality rates were observed for Group 2 or 3, compared with the control group.
      CONCLUSION: Radiation before chemotherapy was a more toxic sequence and,
      surprisingly, carboplatin/etoposide administered in combination with radiotherapy
      was more detrimental than methotrexate. Additional studies are in progress to
      evaluate the toxicity and efficacy of sequences of cranial irradiation and
      enhanced chemotherapy in tumor-bearing rats.

PMID- 9149263
TI  - Efficacy of vancomycin/tri-iododecyclemethyl ammonium chloride-coated
      ventriculostomy catheters in reducing infection.
AB  - OBJECTIVE: The biotoxicity of tri-iododecyclemethyl ammonium chloride (TDMAC)
      coated catheters in the brain was tested, as was the efficacy of the vancomycin
      bonded, TDMAC-coated catheters to inhibit staphylococcal growth in vitro and to
      delay the onset of clinical manifestations of catheter-related staphylococcal
      ventriculitis in rabbit experimental model. METHODS: The brain toxicity of the
      TDMAC-coated catheters was tested in New Zealand White rabbits. The efficacy of
      the vancomycin-bonded, TDMAC-coated catheters in the inhibition of staphylococcal
      growth was tested in agar seeded with Staphylococcus aureus and Staphylococcus
      epidermidis strains. Sections of vancomycin-bonded, TDMAC-coated catheters were
      placed in saline solution for testing of drug release over time. Stereotactic
      placement of ventriculostomy catheters was performed in two groups of New Zealand
      White rabbits. In the experimental group, vancomycin-bonded, TDMAC-coated
      catheters were used. In the control group, TDMAC-coated catheters were used.
      Staphylococcal colonies were inoculated at the exit site of the catheters.
      Culture of the catheter tips was performed at the time of death of the animals.
      RESULTS: No toxic reactions were seen at the implantation sites or in surrounding
      brain. Significant inhibition of growth of both S. aureus and S. epidermidis was
      noted with the vancomycin-bonded catheters (P = 0.01). Vancomycin continued to be
      released from catheters for the full 6 days of the study. The median interval to
      development of clinical manifestations of ventriculitis among the experimental
      group of rabbits was 53 days; among the control group, the interval was 27 days
      (P < 0.001). CONCLUSION: Vancomycin-bonded, TDMAC-coated ventriculostomy
      catheters bind and release the drug at levels exceeding the minimum inhibitory
      concentration for S. aureus and S. epidermidis for at least 6 days and can
      significantly delay the onset of infectious ventriculitis in a rabbit model.

PMID- 9149264
TI  - Transcutaneous pressure-adjustable valves and magnetic resonance imaging: an ex
      vivo examination of the Codman-Medos programmable valve and the Sophy adjustable
      pressure valve.
AB  - OBJECTIVE: We investigated the compatibility of magnetically adjustable
      cerebrospinal fluid valves with clinical magnetic resonance imaging. Torque
      acting on the valves, subjective sensations of valve-carrying volunteers,
      extension of artifacts on acquired images, changes in valve pressure setting, and
      accurate valve function after repeated exposure to the magnetic field were
      tested. METHODS: Two externally adjustable differential pressure valves, i.e.,
      the Codman-Medos programmable valve (Medos S.A., Le Locle, Switzerland) (n = 5)
      and the Sophy programmable pressure valve (Sophysa, Orsay, France) (Model SP3, n
      = 4; Model SU8, n = 3; and Model SM8, n = 2) were exposed to the magnetic fields
      of 1.5-T clinical scanners. Ferromagnetic properties were investigated according
      to an established protocol. Subjective sensations during positioning and scanning
      and image artifacts were investigated using standard clinical imaging protocols.
      Changes in opening pressure setting during repeated magnetic field exposure were
      examined using valves affixed to a dummy. RESULTS: Deflection forces measured 117
      dynes in the Medos valve, and 2439 (Model SP3), 2172 (Model SU8) and 1914 (Model
      SM8) dynes in the Sophy valves. Torque during positioning and during imaging was
      reported for the Sophy valves. Distortion of the magnetic field with artifacts on
      acquired images ranged 6 x 6 x 12 cm around the Sophy valve and 4 x 4 x 4 cm
      around the Medos valves. Artifact extension increased with longer TE times on T2
      weighted images and when using gradient-echo sequences. The pressure setting of
      the Medos valves did not change in 31 of 88 tests. Below 170 mm H2O, the maximal
      disadjustment was 60 mm H2O in each direction. Minor changes of the pressure
      setting were observed at 50 and 30 mm H2O. In 11 of 15 tests at 200 mm H2O, the
      setting after magnetic field exposure was below 30 mm H2O. One Medos valve could
      no longer be programmed after being exposed four times to the static magnetic
      field. Sophy valves remained at or changed to "high" in 68 of 81 tests and to
      "low" in 9. All Sophy valves exhibited paramagnetic behavior after the tests. All
      remained programmable. Observed changes always occurred within the safety area of
      the magnet. CONCLUSION: Subjective disturbances resulting from paramagnetic valve
      behavior are absent in Medos valves and are minor in Sophy valves. Image
      artifacts require careful planning of valve position. Artifacts observed in
      magnetic resonance imaging are less disturbing than those observed in computed
      tomography. Medos valves are more stable regarding disadjustment than are Sophy
      valves. Radiological control of valve setting after exposure to the magnetic
      field is mandatory in both. The 0.5-mT safety line encircling the area that
      patients with pacemakers should not enter is a useful safety borderline for
      patients with pressure-adjustable valves. Failure of the programming mechanism of
      one Medos valve after several exposures to the magnetic field requires
      clarification.

PMID- 9149265
TI  - Lesions in eloquent cortex.

PMID- 9149266
TI  - Dysembryoplastic neuroepithelial tumors located in the caudate nucleus area:
      report of four cases.
AB  - OBJECTIVE AND IMPORTANCE: Dysembryoplastic neuroepithelial tumors (DNTs)
      histologically resemble gliomas but behave as stable lesions. These tumors
      initially were considered to be located exclusively within the supratentorial
      cortex. The four reported cases demonstrate that DNTs may also arise in the area
      of the caudate nuclei. Moreover, the peculiar topography of these lesions, which
      suggests a derivation from the subependymal plate, is in accordance with the
      putative origin of DNTs from secondary germinal layers. CLINICAL PRESENTATION:
      The patients experienced partial seizures (two patients), generalized seizures
      (one patient), or headaches (one patient). All patients were young (17-26 yr) at
      the onset of symptoms, and all had normal results from their neurological
      examinations. INTERVENTION: All lesions demonstrated a pseudocystic appearance on
      computed tomographic scans, were hypointense on T1-weighted magnetic resonance
      imaging scans, hyperintense on T2-weighted magnetic resonance imaging scans, and
      did not show contrast enhancement. The four tumors similarly lined the left or
      right caudate nuclei and expanded within the homolateral ventricle (three
      patients) or both lateral ventricles (one patient). In one patient, the tumor
      also involved the adjacent paraolfactory cortex. CONCLUSION: In all patients,
      stereotactic biopsies helped to identify a specific glioneuronal element of DNTs.
      None of the tumors was operated on. Radiotherapy was performed in only one
      patient. A long pre- and/or postbiopsy imaging follow-up, which was available in
      two nontreated patients (3 yr and 16 yr), demonstrated the perfect stability of
      the lesion. The occurrence of DNTs in this peculiar location needs to be
      considered to avoid misidentification as "ordinary" gliomas and prevent useless
      aggressive treatment.

PMID- 9149267
TI  - Subdural and meaningful involvement related to Wegener's granulomatosis: case
      report.
AB  - OBJECTIVE AND IMPORTANCE: The first case of Wegener's granulomatosis associated
      with subdural empyema is presented. CLINICAL PRESENTATION: A 37-year-old man was
      admitted to our hospital for treatment of bilateral subdural masses. Magnetic
      resonance imaging demonstrated strong bilateral subdural and meningeal
      enhancement. The patient was treated with subdural drainage, based on the
      diagnosis of bilateral subdural hematoma or empyema as revealed by magnetic
      resonance imaging. Even after surgery, he developed systemic symptoms that are
      typical for Wegener's granulomatosis, including hemosputum, papules, peripheral
      nervous disorders, hematuria, myalgia, and joint pain. A diagnosis of Wegener's
      granulomatosis was confirmed by positive circulating antineutrophil cytoplasmic
      antibodies and histological findings from the skin and nasal mucosa. We diagnosed
      the subdural masses as Wegener's granulomatosis from the laboratory and
      neuroimaging studies, retrospectively. INTERVENTION: Pus-like fluid containing
      hematoma with negative micro-organism was evacuated by surgery. CONCLUSION:
      Wegener's granulomatosis should be suspected in young patients with pulmonary
      symptoms and subdural hematoma without head injury. This is the first case of
      Wegener's granulomatosis associated with subdural masses.

PMID- 9149268
TI  - Cytomegalovirus disease presenting as a focal brain mass: report of two cases.
AB  - OBJECTIVE AND IMPORTANCE: Although the differential diagnosis of intracranial
      lesions in patients who have tested positive for human immunodeficiency virus is
      extensive, toxoplasmosis, lymphoma, and progressive multifocal
      leukoencephalopathy comprise approximately 90% of such cases. Cytomegalovirus
      infection of the central nervous system may be difficult to diagnose and rarely
      presents as mass lesions revealed by radiographic studies. CLINICAL PRESENTATION:
      Two patients who had tested positive for human immunodeficiency virus presented
      with progressive focal neurological deficits. Radiographic studies revealed
      solitary contrast-enhancing lesions in the right basal ganglia and right
      cerebellar hemisphere, respectively. INTERVENTION: The first patient underwent a
      stereotactic biopsy but died despite appropriate therapy. The second patient died
      without tissue having been obtained for diagnosis. Postmortem examinations
      revealed necrotizing lesions with diffuse areas of infiltrating histiocytes
      containing eosinophilic cytomegalovirus inclusion bodies. CONCLUSION: Although
      rare, cytomegalovirus infection should be considered in patients who have tested
      positive for human immunodeficiency virus and who present with enhancing
      intracranial lesions.

PMID- 9149269
TI  - Spinal extradural leiomyoma in a pediatric patient with acquired immunodeficiency
      syndrome: case report.
AB  - OBJECTIVE AND IMPORTANCE: We report a case of two separate cervicothoracic,
      extradural leiomyomas occurring in a male pediatric patient with acquired
      immunodeficiency syndrome (AIDS). To our knowledge, such a case has never been
      reported in the literature. CLINICAL PRESENTATION: A 9-year-old male patient with
      AIDS presented with progressive leg weakness. At examination, he was myelopathic
      with paraparesis and a T4 sensory level to pinprick. A magnetic resonance image
      revealed two separate cervicothoracic lesions causing cord compression.
      INTERVENTION: The patient underwent resection of both lesions. Postoperatively,
      he regained normal strength in his legs and was discharged home after 2 weeks.
      CONCLUSION: With the ever-growing number of pediatric patients with AIDS, the
      entity will likely be encountered with increasing frequency in the future.
      Because of the potential for neurological recovery and cure, the neurosurgeon
      should be cognizant of this entity.

PMID- 9149270
TI  - Cervical spinal cord infarction after surgery for a pineal region choriocarcinoma
      in the sitting position: case report.
AB  - OBJECTIVE AND IMPORTANCE: Spinal cord injury is one of several devastating
      complications after operation in the sitting position. Young patients exhibiting
      extraordinary growth spurts demonstrate a higher risk for this complication.
      CLINICAL PRESENTATION: We describe a 7-year-old male patient with a pineal region
      choriocarcinoma in whom a cervical spinal cord infarction (C5-T1) developed as an
      acute complication after operation in the sitting position. Preoperatively, high
      serum levels of human chorionic gonadotropin (5867.7 mIU/ml) and somatomedin-C
      (704 ng/ml) and an extreme growth velocity in height (16 cm/yr) were noted.
      CONCLUSION: It is assumed that, in addition to head flexion, the abnormal
      skeletal growth spurt resulting from an excessive secretion of human chorionic
      gonadotropin from a tumor was a possible predisposing factor for this
      complication. To prevent this complication, surgeons need to pay great attention
      to head positioning, especially in a young patient experiencing an active growth
      spurt.

PMID- 9149271
TI  - Dorsal approach to presacral biopsy: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Biopsy of the presacral space is often awkward,
      technically difficult, and unrewarding when the sacrum is intact and the
      procedure is performed either by open operation or with computed tomographic
      guidance through the abdomen or perineum. CLINICAL PRESENTATION: We describe a
      patient with metastatic adenocarcinoma who presented with leg pain and computed
      tomographic evidence of a high, small mass anterior to an intact sacrum.
      TECHNIQUE: By drilling a hole through the sacrum lateral to the canal and between
      the roots, a biopsy of such a mass may be performed easily, safely, and quickly.
      CONCLUSION: A dorsal approach to presacral biopsy may be easily performed with
      readily available technology.

PMID- 9149272
TI  - Use of a split bone graft to correct the cosmetic deformity associated with the
      transpetrosal-transtentorial surgical approach: technical report.
AB  - OBJECTIVE: Split bone graft reconstruction was performed after a standard
      transpetrosal-transtentorial approach to correct the cosmetic deformity in 18
      patients. TECHNIQUE: The split bone graft was made by dividing the inner table of
      the temporosuboccipital bone graft and covered the bone effect created by
      petrosectomy and mastoidectomy. The split bone graft was created and shaped
      during closure of the dura, so that the operation was not prolonged. RESULTS:
      This technique produced excellent cosmetic results immediately after surgery; the
      results were maintained during the follow-up period of between 20 and 46 months.
      No complication associated with this technique was recognized. CONCLUSION: Split
      bone graft reconstruction is a simple and safe technique for preventing the
      cosmetic deformity associated with a transpetrosal-transtentorial approach.

PMID- 9149273
TI  - The EasyGuide Neuro image-guided surgery system.

PMID- 9149274
TI  - Tew cranial/spinal retractor.

PMID- 9149275
TI  - Continuous monitoring of partial pressure of brain tissue oxygen in patients with
      severe head injury.

PMID- 9149276
TI  - Foville's plate 6.

PMID- 9149277
TI  - Outcome of surgical decompression of the second cervical root for cervicogenic
      headache.

PMID- 9149278
TI  - Comparison of surgical treatments for trigeminal neuralgia: reevaluation of
      radiofrequency rhizotomy.

PMID- 9149279
TI  - Magnetic resonance image-guided stereotactic cingulotomy for intractable
      psychiatric disease.

PMID- 9149280
TI  - Intraoperative angiography in cerebral aneurysm surgery: a prospective study of
      100 craniotomies.

PMID- 9149281
TI  - Lipoprotein (a): a potential biological marker for unruptured intracranial
      aneurysms.
AB  - OBJECTIVE: The diagnosis and treatment of intracranial aneurysms (IAs) prior to
      rupture reduces the high morbidity and mortality associated with their
      occurrence. Elevated serum lipoprotein (a) [Lp(a)] level, an independent risk
      factor for atherogenesis, has been demonstrated in sporadic IA disease (1). The
      purpose of this study was to assess the degree of correlation between elevated
      Lp(a) levels and the occurrence of IAs in asymptomatic first degree relatives of
      index cases from three families exhibiting a familial tendency towards IA
      development. METHODS: 25 family members and 41 healthy controls were screened by
      random serum Lp(a) sampling. All family members received 4-vessel cerebral
      angiography. RESULTS: Eleven family members were found on angiography to harbour
      asymptomatic aneurysms and all were successfully treated by surgery. Of these 11,
      ten had significantly raised serum Lp(a) levels (> 30 mg%). Fourteen family
      members had negative angiograms. Eight of this latter group, mean age 43.6 +/-
      3.8 years, had serum Lp(a) levels above the normal range. Mean Lp(a) levels were
      53.7 +/- 1.2 mg% in subjects with aneurysms compared with 22.1 +/- 1.45 mg% in
      subjects without demonstrable aneurysms and 10.5 +/- 0.48 mg% in the control
      population. CONCLUSION: The prevalence of elevated Lp(a) levels in these families
      and the high degree of association of raised Lp(a) levels with the presence of
      IAs in several family members warrants follow up of angiographically negative
      young subjects. We require a case-control study to establish whether particular
      polymorphisms at the apoprotein (a) gene level are associated with the occurrence
      of IAs in these families.

PMID- 9149282
TI  - Immunomodulation by hydatid cyst fluid toxin (Echinococcus granulosus).
AB  - Since the experimental infection by hydatid cysts (Echinococcus granulosus) in
      mice causes immunomodulation of the host, the effects of hydatid fluid (HF) and
      fractions of HF were compared in vitro and in vivo. Fractions of HF were obtained
      using ammonium sulphate precipitation, chloroform/methanol extraction and thin
      layer chromatography (TLC). HF proved to be toxic to murine peritoneal
      macrophages in vitro, and when macrophages were incubated with the different
      fractions of HF, most toxicity was found in a single TLC-purified fraction with
      an adjuvant-like effect on the production of specific antibodies against bovine
      albumin and human red blood cells in mice. Treatment of mice with the toxin
      caused a drop in the percentage of peripheral blood lymphocytes. Flow-cytometric
      analysis showed that T-cells from toxin-treated mice had lower membrane-CD3, CD4
      and CD8 density, and higher percentages of CD8+ splenocytes and CD4+ thymocytes
      expressing CD25. The toxin caused a down-regulation of CD4 and CD8 expression on
      thymocytes in vitro, that was dependent on the presence of macrophages. The
      results may attribute to these toxins a role in the host-parasite relationship of
      hydatidosis.

PMID- 9149283
TI  - Antigenicity and immunogenicity of multiple antigen peptides (MAP) containing P.
      vivax CS epitopes in Aotus monkeys.
AB  - Using linear synthetic peptides corresponding to the Plasmodium vivax
      circumsporozoite (CS) protein of the common type, we have identified several T
      and B-cell epitopes recognized by human individuals. Three T-cell epitopes
      studied (p6) from the amino, (p11) from the central and (p25) from the carboxyl
      regions, were widely recognized by lymphocytes of immune donors. A series of six
      peptides, in addition to p11, representing the central repeat domain of the
      CS(p11-p17) protein were used in ELISA assays to map the B-cell epitopes of this
      region. P11 was the peptide most frequently recognized by sera containing
      antibodies to the homologous CS protein as determined by IFAT. The sequences
      corresponding to peptides p6, p11 and P25 as well as that representing a
      universal T-cell epitope derived from the tetanus toxin were used to assemble
      eight different Multiple Antigen Peptides (MAP). The immunogenicity of these MAP
      was analysed in Aotus monkeys. Groups of two animals were immunized with each MAP
      and both antibody response, T-lymphocyte proliferation and in vitro gamma-IFN
      production were evaluated. Two MAPs containing the same B-cell epitope and either
      a promiscuous CS-protein derived T-cell epitope (p25) or the tetanus toxin
      epitope (p-tt30) proved to be the most immunogenic and induced high levels of
      anti-peptide antibodies that recognized the native protein. Except for animals
      immunized with MAP VII, there was no correlation between antibody levels,
      lymphocyte proliferation or gamma-IFN production in vitro. The broad recognition
      of these epitopes by individuals which had been exposed to malaria, the capacity
      of these MAPs to induce antibodies, recognize the cognate protein, and in vitro
      gamma-IFN production encourages further analyses of the potential of these
      proteins as malaria vaccine candidates for human use.

PMID- 9149284
TI  - Modelling Trypanosoma congolense parasitaemia patterns during the chronic phase
      of infection in N'Dama cattle.
AB  - We reanalyzed parasitaemia profiles of the trypanotolerant N'Dama cattle (Bos
      taurus), consecutively infected with the same four clones of Trypanosoma
      congolense. Our analysis shows that each individual parasitaemia is characterized
      by progressively longer intervals between parasites waves. This pattern is most
      visible during the chronic phase of infection. In addition, the last of the four
      infections had a significantly larger overall duration of inter-wave intervals.
      We retrieved these patterns by numerical simulations of a mathematical model,
      which incorporates assumptions about the molecular basis of antigenic variation
      and about the anti-parasitic major immune processes. Six potential factors that
      may determine parasitaemia pattern were studied: carrying capacity of the host
      environment, intrinsic growth rate of the parasite, affinity maturation of the
      immune response, immune cell birth and death rate, levels of antibodies to
      variant surface glycoprotein and levels of antibodies to invariant antigens. Our
      simulations suggest that the first five factors are not likely to determine the
      chronic phase parasitaemia pattern whereas the sixth one, namely, antibody
      response to invariant antigens, yielded profiles consistent with the experimental
      data. Being cumulative, the immune response to anti-invariant antigens may be
      increasingly effective as infection proceeds and in successive infections.
      Comparisons between N'Dama and Zebu and between chronic and acute phases will be
      needed to make a statement on the role of this phenomenon in trypanotolerance.

PMID- 9149285
TI  - Intranasal administration of Schistosoma mansoni adult worm antigen in
      combination with cholera toxin induces a Th2 cell response.
AB  - Mice immunized with soluble adult worm antigen (SWAP) in combination with cholera
      toxin (CT) displayed significantly larger numbers of IgG1, IgM and IgA secreting
      cells in the spleen and in the lungs as compared to mice which had received SWAP
      only. The ratio of SWAP-specific IgG1 to IgG2a antibody-secreting spleen cells
      was also significantly higher in the SWAP-CT group. Analysis of cytokine
      responses revealed that SWAP-stimulated spleen and lung cells from the SWAP-CT
      group produced lower levels of IFN-gamma but higher levels of IL-4 and IL-5 as
      compared to cells from the SWAP group. These findings indicate that intranasal
      administration of SWAP-CT induces a Th2 cell response in the spleen and in the
      lungs. Our findings also suggest that CT was responsible for induction of this
      Th2 cell response, since intranasal administration of SWAP alone induced a Th1
      type response in the spleen and in the lungs.

PMID- 9149286
TI  - Antibodies to diethylcarbamazine potentiate the antifilarial activity of the
      drug.
AB  - The antifilarial drug diethylcarbamazine citrate (DEC) is known to mediate in
      vivo microfilaricidal activity in conjunction with the host immune system. In
      this study passive transfer of antibodies to DEC elicited by immunization with
      methyl piperazine carboxylic acid (MPCA) coupled to bovine serum albumin (BSA),
      was found to potentiate microfilaricidal activity of subcurative doses of DEC in
      Setaria digitata infected Mastomys coucha. Active immunization of microfilaraemic
      animals with MPCA-BSA followed by administration of subcurative doses of DEC also
      resulted in rapid clearance of microfilaraemia in both S. digitata and Brugia
      malayi infected M. coucha indicating the synergistic activity of DEC and the
      antibodies to the drug. Since some of the filarial antibodies are known to react
      with DEC, it is proposed that such antibodies may potentiate the microfilaricidal
      activity of the drug in vivo.

PMID- 9149287
TI  - Opioid peptide modulation of circulatory and endocrine response to mental stress
      in humans.
AB  - Healthy subjects were classified according to their percent increase in systolic
      blood pressure (SBP) after mental arithmetic test (MAT) as low (delta SBP 9.3
      15.1%, n = 15) and high (delta SBP 35.1-45.4%, n = 15) responders. During MAT,
      low responders showed significantly (p < 0.01) increased plasma levels of beta
      endorphin, cortisol, catecholamines, and atrial natriuretic factor (ANF) and
      decreased levels of endothelin-1, whereas high responders showed increased (p <
      0.01) levels of Metenkephalin, dynorphin B, and catecholamines. Pretreatment with
      naloxone hydrochloride enhanced (p < 0.01) SBP, heart rate, noradrenaline,
      cortisol, and endothelin-1 levels, and reduced (p < 0.01) ANF in low responders
      in response to MAT, whereas it decreased (p < 0.01) hemodynamic parameters,
      noradrenaline, and endothelin-1 in high responders. The individual differences in
      hemodynamic and endocrine responses to MAT may depend on a different activation
      of the endogenous opioid system.

PMID- 9149288
TI  - An amphipathic alpha-helical synthetic peptide analogue of melittin inhibits
      herpes simplex virus-1 (HSV-1)-induced cell fusion and virus spread.
AB  - The effects of hecate, a 23-amino acid synthetic peptide analogue of melittin, on
      HSV-1-induced cell fusion and virus multiplication was investigated. Hecate
      completely inhibited cell fusion induced by HSV-1 syncytial (syn) mutants HSV-1
      HFEM (tsB5) and HSV-1 mp (MP) at a concentration of 5.0 microM. Metabolic
      labeling experiments indicated that hecate did not adversely affect cellular
      growth and protein synthesis. The synthesis of virus-specified glycoproteins B,
      C, D, and H was reduced in the presence of hecate; however, the transport of
      these glycoproteins to the surface of infected cells was not affected. Production
      of infectious virions for wild-type and syn mutants tsB5 and MP was reduced in
      the presence of hecate. The effect of hecate on virus titer was dependent on the
      multiplicity of infection. Virus titers were reduced 2-28-fold at an M.O.I. of
      0.1, 3-6-fold at an M.O.I. of 0.5, and 0-2.5-fold at an M.O.I. of 2.5. Direct
      treatment of semipurified virions with hecate reduced titers by approximately 4
      fold for KOS, 2-fold for tsB5, and over 30-fold for MP.

PMID- 9149289
TI  - Prevention of ACTH- and adrenalectomy-induced muricidal behavior: by
      benzodiazepinic ligands.
AB  - We investigated the effect of treatment with central (neuronal and glial)
      benzodiazepine binding site-active molecules on ACTH- or adrenalectomy (ADX)
      induced muricidal behavior in male Wistar rats. Pretreatment (IP) with either
      flumazenil or clonazepam prevented the subsequent induction of ADX-induced
      behavior, but only flumazenil protected against ACTH-induced behavior;
      posttreatment in both cases induced no significant modifications. Using 4'-chloro
      diazepam or PK 11195, both pre- and posttreatment afforded protection, the effect
      lasting longer (> 1 week) than that induced by flumazenil or clonazepam (2 days).
      Pretreatment with the GABAA agonist, muscimol, also resulted in complete
      protection, whereas posttreatment had only a slight effect.

PMID- 9149290
TI  - Arginine-vasopressin stimulates CRH and ACTH release by rat adrenal medulla,
      acting via the V1 receptor subtype and a protein kinase C-dependent pathway.
AB  - Arginine-vasopressin (AVP) is a hypothalamic hormone that, like CRH, stimulates
      the pituitary release of ACTH, thereby activating adrenal glucocorticoid
      secretion. Evidence indicates that rat adrenal medulla contains a CRH-ACTH system
      duplicating that existing at the hypothalamo-pituitary level and involved in the
      paracrine stimulation of the cortex secretion. Therefore, we investigated by RIA
      the effect of AVP on the release of CRH and ACTH immunoreactivities (IR) by rat
      adrenal medulla in vitro. AVP concentration-dependently enhanced the release of
      both CRH-IR and ACTH-IR, and the effect was blocked by a selective antagonist of
      the V1 subtype of AVP receptors. The CRH receptor antagonist alpha-helical-CRH
      partially reversed AVP-evoked rise in ACTH-IR release, without altering either
      CRH response or basal secretions of CRH and ACTH. The specific inhibitors of
      protein kinase C Ro31-8220 and calphostin C abolished both CRH and ACTH responses
      to AVP. In conclusion, our present findings suggest that AVP stimulates
      intramedullary the CRH-ACTH system, acting via V1 receptors and activating
      protein kinase C.

PMID- 9149291
TI  - Intra-arcuate opiate actions stimulate GRF-dependent and protein-selective
      feeding.
AB  - Growth-hormone releasing factor (GRF) induces feeding and growth hormone (GH)
      release. Opiates activate GRF neurons regulating GH release. This study sought to
      determine whether opiate actions on GRF neurons would also stimulate feeding. In
      Experiment 1, Wistar male rats received intra-arcuate morphine (0, 1, 10, and 20
      micrograms/0.5 milligrams) which increased protein intake/feeding activity. In
      Experiment 2, this effect was blocked when Wistar male rats received intra
      SCN/MPOA pretreatments with GRF antiserum followed by intra-arcuate morphine (1
      microgram/0.5 milligrams) injections. The data suggest that an opioid trigger may
      stimulate complementary central (feeding effects) and peripheral (GH release) GRF
      actions via the arcuate nucleus.

PMID- 9149292
TI  - Differential effects of baseline macronutrient preferences on macronutrient
      selection after galanin, NPY, and an overnight fast.
AB  - Rats display individual patterns of fat and carbohydrate intakes when allowed to
      self-select among individual macronutrient diets. We investigated whether these
      individual preferences in macronutrient selection could be modified by an
      overnight fast or by two orexigenic peptides, galanin and neuropeptide Y (NPY),
      which may selectively stimulate fat and carbohydrate intake. Rats were grouped by
      preference based on the ratio of average baseline fat:carbohydrate intake. In
      counterbalanced tests conducted on separate days, saline, galanin, or NPY was
      infused into the paraventricular nucleus of the hypothalamus and 60-min food
      intake was measured. When the macronutrient intakes were expressed as percent of
      total caloric intake, galanin administered into the PVN did not increase fat
      consumption compared to saline injection in either preference group. NPY slightly
      enhanced the proportion of carbohydrate intake, but only in carbohydrate
      preferring rats. When all three feeding stimuli were compared to baseline
      preferences, the only condition that significantly altered macronutrient
      selection was an overnight fast, which augmented fat intake. These data
      demonstrate that baseline preferences for fat or carbohydrate are not
      significantly modified by galanin or NPY but that an overnight fast increases fat
      preference.

PMID- 9149293
TI  - Intracisternal TRH and RX 77368 potently activate gastric vagal efferent
      discharge in rats.
AB  - The influence of intracisternal (ic) TRH and the stable TRH analog, RX 77368, on
      gastric vagal efferent discharge (GVED) was investigated in urethane-anesthetized
      rats. Consecutive IC injections of TRH (3, 30, and 300 ng) at 60 min intervals
      stimulated dose dependently multi-unit GVED with a peak increase of 90 +/- 21%,
      127 +/- 18% and 145 +/- 16% respectively. In two separate studies, IC injection
      of RX 77368 at 1.5 or 15 ng stimulated multi-unit GVED by 142 +/- 24% and 244 +/-
      95% respectively. Saline injection IC had no effect on GVED. RX 77368 (1.5 ng,
      ic) action was long lasting (84 +/- 13 min) compared with TRH (3 ng: 44 +/- 7
      min). Single-unit analysis also showed that 13 of 13 units responded to ic RX
      77368 (1.5 ng) by an increase in activity. These data indicate that low doses of
      TRH injected ic stimulate vagal efferent outflow to the rat stomach and that RX
      77368 action is more potent than TRH.

PMID- 9149294
TI  - The distribution of NPY-containing nerves and the catecholamine contents of
      canine enteric nerve plexuses.
AB  - Our previous study demonstrated that PYY was a major neuropeptide in the canine
      enteric nervous system, the present study defines the locations of NPY-containing
      enteric neurons. NPY-positive nerve cell bodies and fibers were numerous in
      gastric and pyloric myenteric plexuses as were positive nerve fibers in antral
      and pyloric muscle layers, pyloric sphincter muscle layers, and surrounding blood
      vessels. In contrast to findings for PYY, there were considerably fewer NPY
      positive nerve cell bodies and fibers in the canine ileum and colon.
      Noradrenaline was the predominant catecholamine in all plexuses, the rank order
      of its contents being: deep muscular > submucous > myenteric plexus. The
      dopamine/noradrenaline ratio was constant in all plexuses; adrenaline was present
      in minor amounts. PYY is the more abundant neuropeptide in ileum and colon, and
      NPY has a greater presence in the gastric antrum, pylorus, and surrounding blood
      vessels. PYY and NPY may play different functional roles in the GI tract.

PMID- 9149295
TI  - Hemodynamic profile of neuropeptide Y in dogs: effect of ganglionic blockade.
AB  - The hemodynamic effects of neuropeptide Y (NPY) were examined over a dose range
      of 0.03-30 nmol/kg, i.v., in anesthetized open-chest, ventilated dogs with and
      without ganglionic blockade. In normal (non-ganglion-blocked) animals, NPY
      produced significant, dose-dependent, and sustained (lasting 15-45 min) increases
      in mean arterial blood pressure and systemic vascular resistance (SVR) with a
      threshold dose of 0.3 nmol/kg and a maximum effective dose of 10 nmol/kg. Cardiac
      index (CI) decreased at doses > 1 nmol/kg, but stroke volume was not altered;
      heart rate (HR) decreased significantly at and above the 3 nmol/kg dose. No
      significant changes were observed in the left ventricular dP/dt (LVdP/dt) or the
      contractility index (LVdP/dt divided by systolic pressure). In ganglion-blocked
      animals, pressor and SVR responses to NPY were similar to those seen in normal
      animals but HR was not affected and a small but significant decrease in CI was
      seen only at the 30 nmol/kg. Furthermore, whereas LVdP/dt of ganglion-blocked
      dogs increased significantly at and above the 1 nmol/kg dose, the contractility
      index increased slightly only with the 10 and 30 nmol/kg doses. These data
      indicate that NPY produces sustained hypertension in dogs secondary to peripheral
      vasoconstriction, has a weak, direct positive inotropic action on the heart, and
      lacks chronotropic effects.

PMID- 9149296
TI  - Interactions between angiotensin II and delta opioid receptor subtype agonists
      upon water intake in rats.
AB  - Delta opioid receptor agonists, like those of mu and kappa receptors, stimulate
      water intake. To assess the relative contributions of delta1 and delta2 receptors
      in the modulation of water intake stimulated by Angiotensin II (AII), the present
      study examined the respective actions of [D-Pen2, D-Pen5]-enkephalin (DPDPE: 5-20
      ug, i.c.v.) and [D-Ala2, Glu4]-Deltorphin (Delt II: 5-20 ug, i.c.v.) upon water
      intake per se, and upon AII (0.02-20 ng, i.c.v.)-induced hyperdipsia in rats.
      Both DPDPE and Delt II dose-dependently stimulated spontaneous water intake. An
      ineffective (5 ug) dose of DPDPE differentially altered water intake when paired
      with AII, significantly increasing intake at the 0.02 ng dose, not changing
      intake at the 0.2 ng dose and significantly decreasing intake at the 2 ng dose.
      In contrast, pairing ineffective doses of Delt II (5 ug) and AII (0.2 ng)
      significantly increased water intake that persisted when either the Delt II dose
      (1 ug) or the AII dose (0.02 ng) was lowered. However, neither delta1 nor delta2
      opioid agonists significantly altered the ED50 for AII-induced drinking. Thus,
      delta2 opioid agonism appeared more consistent and reliable than delta1 opioid
      agonism in stimulating water intake when paired with AII, and these data indicate
      interactions between delta1 and delta2 agonists and AII in mediating water
      intake.

PMID- 9149297
TI  - Increased endothelin ET(A) receptor expression in rat carotid arteries after
      balloon injury.
AB  - Endothelins are vasoactive peptides and are believed to act as vascular smooth
      muscle mitogens. Vascular injury results in medial smooth muscle migration and
      proliferation with the formation of a neointima. Using quantitative
      autoradiography, we examined the expression of endothelin receptor subtypes ET(A)
      and ET(B) in the rat carotid artery 2, 8, and 16 days after balloon-catheter
      injury. At two and eight days after balloon catheterization, ET(A) receptor
      expression was significantly increased in the media of the injured vessel when
      compared to that in the media of the intact vessel. The enhanced expression of
      receptors returned to normal levels by 16 days after the injury. Neointimal cells
      also expressed ET(A) receptors at a lower level than that expressed by the
      injured media 8 days after injury, and continued to express ET(A) receptors 16
      days after the injury. ET(B) receptors were not detectable in the media or the
      neointima at any time after the injury. Our results suggest the ET(A) receptors
      may have a significant role in injury induced vascular smooth muscle
      proliferation and neointima formation.

PMID- 9149298
TI  - Somatostatin does not affect multiplication of granule cells in the rat
      cerebellum.
AB  - Somatostatin receptor are transiently expressed by immature granule cells of rat
      cerebellum. The effects of somatostatin and octreotide on cell proliferation were
      studied in cultured cerebellar explants from 10-day-old rats. Cell multiplication
      was measured using [3H]thymidine incorporation and flow cytometric analysis of
      cell cycle parameters. [3H]Thymidine incorporation occurred exclusively in
      neuroblasts of the external granule cell layer in the presence of insulin (1
      microM). The labeling index, the length of the S phase, and the potential
      doubling time were similar in vivo and in explants. Octreotide (10(-12) to 10(
      6)M) had no effect on [3H]thymidine incorporation in cerebellar explants. In
      addition, somatostatin and octreotide did not modify the proportion of cells in
      the S, G0-G1, and G2-M phases. The present results demonstrate that somatostatin
      does not affect cell multiplication in neurons of the external granule cell
      layer.

PMID- 9149300
TI  - Ischemic-reperfused rat skeletal muscle: the effect of vasoactive intestinal
      peptide (VIP) on contractile force, oxygenation and antioxidant enzyme systems.
AB  - The effect of vasoactive intestinal peptide (VIP) on the nerve-stimulated
      contraction, tissue oxygenation, lipid peroxidation and antioxidant enzymes
      activities-superoxide dismutase and catalase was investigated in the rat
      gastrocnemius muscle exposed to 4 h ischemia-4hr reperfusion. Ischemia caused
      significant decrease in muscle contractile force, oxygenation and superoxide
      dismutase enzyme activity. Reperfusion of ischemic muscle increased the muscle
      contractile force and restored the tissue oxygenation to the baseline level.
      Superoxide dismutase and catalase activities of reperfused muscle increased
      significantly. However neither ischemia nor reperfusion affected gastrocnemius
      muscle malondialdehide (MDA) levels. VIP administration at the onset of
      reperfusion significantly increased skeletal muscle contractile force and tissue
      oxygenation even higher than baseline and reperfusion values. VIP also normalized
      the increased superoxide dismutase and catalase activities of reperfused skeletal
      muscle. In conclusion, VIP, acting as a powerful antioxidant and preserving
      contractile machinery seems to be a promising endogenous peptide that can salvage
      the skeletal muscle from severe ischemia-reperfusion injury.

PMID- 9149299
TI  - VIP fibers in rat optic chiasm and optic nerve arising from the hypothalamus.
AB  - This is the first report showing VIP fibers in the optic chiasm and the optic
      nerves of intact rats. These fibers form a fan-shaped dorso-medial bundle in the
      optic nerves. After colchicine injection into the vitreous body VIP fibers could
      be followed farther in the optic nerve toward the eye when compared to intact
      rats. After removal of eyes (enucleation) the VIP fiber-bundle became more
      prominent and VIP immunoreactive perikarya appeared in the supraoptic and para
      ventricular nuclei. When five-nine months after the enucleation Phaseolus
      vulgaris leucoagglutinin was administered to the paraventricular or supraoptic
      area, the anterogradely transported tracer was demonstrated in the optic nerve.
      These observations suggest the existence of a hypothalamic projection to the eye,
      which is, at least in part, VIP immunoreactive.

PMID- 9149301
TI  - Effect of substance P and receptor antagonists on secretion of lingual lipase and
      amylase from rat von Ebner's gland.
AB  - Substance P (SP, 1 microM) when incubated with minced von Ebner's glands for 15,
      30, and 60 min, stimulated secretion of lingual lipase (12.14% +/- 0.90) and
      amylase (8.30% +/- 0.42). Only 10 microM of the SP receptor antagonist CP-96,345
      significantly inhibited SP-evoked secretion. D-Pro2-D-Phe7-D-Trp9-SP (Ia), D-Pro2
      D-Trp7,9-SP (Ib), D-Arg1-D-Trp7,9-D-Leu11-SP (Ic), or 1 microM CP-96,345 were not
      effective, suggesting that the SP receptor of von Ebner's gland might be an
      isoform. Propranolol and timolol, beta 1/beta 2-adrenergic receptor antagonists
      were not effective and the cholinergic receptor antagonist, atropine, was
      effective in only slightly reducing amylase secretion but not lingual lipase.
      Differential secretion of the two enzymes was observed for basal and stimulated
      secretion. Thus, exocytosis may not be the only pathway involved in SP-evoked
      protein secretion.

PMID- 9149302
TI  - Neuropeptide FF in the rat spinal cord during carrageenan inflammation.
AB  - The role of neuropeptide FF (NPFF) in the modulation of spinal nociception was
      studied in rats with carrageenan inflammation in the hind paw. Normally no NPFF
      ir neuronal cell bodies are found in the spinal cord. During inflammation NPFF
      neurons were seen in an area receiving innervation from the inflamed hind limb,
      but in rats pretreated with morphine no NPFF-ir neurons were found. NPFF or IgG
      from NPFF immunoserum administered intrathecally had no effect in thermal and
      mechanical nociceptive tests. Morphine produced significant antinociception in
      both tests in the inflamed paw, but the effect was not modified by NPFF. These
      findings differ from the effects of intrathecal administration of NPFF and
      opioids in acute thermal tests when no inflammation is present. The role of NPFF
      in the modulation of nociception in the spinal cord may be markedly changed
      during acute inflammation.

PMID- 9149303
TI  - Hemorphin peptides are released from hemoglobin by cathepsin D. radioimmunoassay
      against the C-part of V-V-hemorphin-7: an alternative assay for the cathepsin D
      activity.
AB  - In order to investigate the putative physiological role of the in vivo release of
      hemorphins from hemoglobin in tissues, an immunological approach was developed.
      Specific and sensitive antiserum were raised against the C-part of the V-V
      hemorphin-7. The antisera recognized to the same extent the related hemorphins V
      V-hemorphin-7 and L-V-V-hemorphin-7. The validity of our immunological approach
      was analyzed by studying the in vitro release of hemorphin from hemoglobin by
      cathepsin D and compared to the pepsin hydrolysis. These two enzymes led to the
      release of these same products suggesting that cathepsin D acted as an accurate
      pepsin-like enzyme. Moreover, considering the poor sensitivity of the available
      methods of detection for the in vitro Cathepsin D activity, our specific and
      sensitive V-V-hemorphin-7 radioimmunoassay seems to be a useful alternative assay
      for this enzymatic activity.

PMID- 9149304
TI  - Five out of six tryptophan residues in the N-terminal extracellular domain of the
      rat GLP-1 receptor are essential for its ability to bind GLP-1.
AB  - Oligonucleotide-directed mutagenesis was utilized to investigate the requirement
      of tryptophan residues located in the N-terminal domain of the glucagon-like
      peptide-1 (GLP-1) receptor for the ability to bind its ligand and to induce cAMP
      generation. W39, W72, W87, W91, W110, and W120 were mutated into alanine. Two of
      the six tryptophan residues, W72 and W110, are highly conserved within the
      receptor subfamily. After transfection of mutated cDNAs in COS-7 or CHL cells, it
      appeared that mutant W87 A bound [125I] GLP-1 with the same affinity as wild-type
      receptor and induced signal transduction to a comparable extent. In contrast,
      mutant receptors W39A, W72A, W91A, W110A, and W120A lost the ability to bind
      [125I] GLP-1. Because all mutated receptor cDNAs were transcribed on RNA level
      (Northern blot) and the receptor proteins were expressed at the plasma membrane
      level (Western blot), it is concluded that with the exception of W87 all
      trytophan residues are essential for receptor ligand interaction. This indicates
      the significance of hydrophobic interactions within the N-terminal domain of the
      GLP-1 receptor.

PMID- 9149305
TI  - Expression of the calcitonin gene family in medullary thyroid carcinoma.
AB  - The regulatory peptide calcitonin was discovered in 1962. During the last decade
      it has been demonstrated to be part of a gene family. Calcitonin is synthesized
      in the parafollicular cells (C cells) of the thyroid gland. These cells give rise
      to an endocrine tumor, medullary thyroid carcinoma (MTC), which is found in a
      sporadic and an inherited form. Calcitonin is used as a tumor marker for MTC. The
      calcitonin gene was demonstrated in 1981 to give rise to an alternative peptide
      product, alpha-CGRP, and a second gene encoding a very similar peptide, beta
      CGRP, has also been identified. A third CGRP-like peptide, amylin, was identified
      in 1986. This article summarizes the present knowledge about gene structure,
      regulation of gene expression, and expression of the calcitonin gene family in
      MTC and in MTC-derived cell lines. The methods employed for detection of gene
      expression and for measurement and characterized of peptide products are
      described, and finally the relevance of biochemical tumor markers is discussed in
      relation to the new diagnostic methods for inherited MTC based on molecular
      biological techniques.

PMID- 9149306
TI  - Fluorescein-Trp25-exendin-4, a biologically active fluorescent probe for the
      human GLP-1 receptor.
AB  - Exendin-4, a reptilian GLP-1 analogue, has been fluorescently labeled by
      covalently linking a fluorescein moiety onto the Trp residue yielding fluorescein
      Trp25-exendin-4 (FLEX). FLEX is equipotent to GLP-1(7-36)-amide and exendin-4 as
      an inhibitor of [125I] GLP-1 binding to the human GLP-1 receptor stably expressed
      in CHO cells, and maintains full biological potency and efficacy as measured by
      the stimulation of cAMP accumulation in these cells. FLEX binding to CHO/hGLP-1R
      membranes results in an increase in fluorescence anisotropy. The binding is
      specific and saturable (Kd = 2.0 +/- 0.4 nM), and GLP-1(7-36)-amide and exendin-4
      are equipotent inhibitors of FLEX binding to the human GLP-1 receptor. Thus, FLEX
      is a potent, biologically active ligand that is useful for the study of the
      binding and functional characteristics of the human GLP-1 receptor.

PMID- 9149307
TI  - Neurogenic substance P stimulates osteogenesis in vitro.
AB  - Previous studies have shown that there is colocalization of substance P (SP) and
      calcitonin gene-related peptide (CGRP) immunoreactive nerve fibers in bone,
      periosteum and bone marrow. Because SP may also possibly play a role in bone
      formation, we decided to test whether it has an osteogenic stimulating effect on
      developing bone in vitro. To this end, 0.4, 4 and 40 micrograms/ml of SP in BGJb
      medium was added daily to 3 million light density (LD) bone marrow white cells
      which were separated by Ficoll-Paque density gradient separation then seeded onto
      a previously prepared fibroblast feeder layer in Petri dishes. Seven days after
      adding SP, in the control without SP there were 2 bone colonies; with 0.4
      micrograms of SP there were 3 colonies; with 4 micrograms there were 5 colonies;
      with 40 micrograms there were 7 colonies. In addition, there was an increase in
      the size of bone colonies in the SP-added group. The results indicated that SP
      had a dose-related osteogenic stimulating effect. The increase in the number and
      size of bone colonies by SP was probably caused by stimulating stem cell mitosis,
      osteoprogenitor cell differentiation or osteoblastic activity.

PMID- 9149309
TI  - Rate of absorption.

PMID- 9149308
TI  - Effects of Cuban red propolis on galactosamine-induced hepatitis in rats.
AB  - Using transmission electron microscopy and biochemical analysis, the effect of
      cuban red propolis against hepatitis induced by 1,000 mg kg-1 of galactosamine in
      rats was studied. An ethanolic extract of propolis was prepared and it was given
      to rats at doses of 10, 50 and 100 mg kg-1, 30 min before the hepatotoxin.
      Propolis extract prevented hepatocytes alterations induced by galactosamine. It
      was mainly seen in rough endoplasmic reticulum, Golgi complex, nucleus and plasma
      membrane of hepatocytes. Propolis extract induced reversion of the increased
      activity of alanine aminotransferase and malondialdehyde concentration in the
      serum of rats treated with galactosamine. The probable role of antioxidant
      activity of propolis in the prevention of hepatitis is discussed in this paper.

PMID- 9149310
TI  - Galanin, galantide and galanin (1-14)-[alpha-aminobutyric acid8]-scyliorhinin-I:
      structure dependent effects on the rat isolated gastric fundus.
AB  - The study was undertaken using selected pharmacodynamic parameters to describe
      the effects of porcine galanin(1-29)-NH2; porcine galanin fragments; galantide;
      porcine galanin(1-14)-[alpha-aminobutyric acid8]scyliorhinin-I and the analogues
      of the latter peptides on rat isolated gastric fundus muscle. All tested
      peptides, apart from galanin(16-29)-NH2 evoked reproducible concentration
      dependent contractions with significantly decreased activities in comparison to
      the potency of the native galanin(1-29)-NH2 molecule. The order of the
      contractile ability in the group of galanin(1-29)-NH2 short fragments was as
      follows: [lysine14]galanin(1-15)-NH2 > galanin(1-15)-OH > galanin(1-15)-NH2 >
      [glycine5] galanin(1-15)-NH2 > galanin(2-15)-NH2 > [glycine5,lysine14]galanin(1
      15)-NH2. Aside from [lysine14]galanin(1-15)-NH2 which had a lower efficacy, none
      of the peptides showed significant changes in this respect in comparison to the
      intact galanin(1-29)-NH2 molecule. The concentration-response curves of the
      tested peptides were to the right and their slopes besides from: galanin(1-15)
      OH; galanin(2-15)-NH2; [glycine5]galanin(1-15)-NH2 remained not significantly
      different from galanin(1-29)-NH2. Hill's coefficient for galanin(1-29)-NH2 is
      1.03 indicating an interaction of one galanin(1-29)-NH2 molecule with one
      receptor, fulfilling criteria of classical receptor theory. For galanin fragments
      Hill's coefficients are < 1 implying that the rules of classical theory may not
      apply. Galantide and analogues exhibited a subsequent decrease in potency:
      [cycloleucine4] galantide > galantide > [homoserine6]galantide >
      [phenylalnine(4fluor)17] galantide. Galanin(1-14)-[alpha-aminobutyric acid8]
      scyliorhinin-I and its analogues contracted the gastric fundus with a decline in
      strength: galanin(1-13)-[norleucine10]-scyliorhinin-I(3-10) > galanin(1-13)
      [phenylalanine(4fluor)7]-scyliorhinin-I > galanin(1-14)-[alpha-aminobutyric
      acid8]-scyliorhinin-I > galanin(1-13)-[alpha-aminobutyric acid8, norleucine10]
      scyliorhinin-I(3-10). They all displayed a greater efficacy than galanin(1-29)
      NH2, and the concentration-response curves were slightly to the right, almost
      parallel to that of galanin(1-29)-NH2. Slopes of the curves were not
      significantly different from galanin(1-29)-NH2. Hill's coefficient for the
      galantide, [cycloleucine4]galantide; [homoserine6]galantide;
      [phenylalanine(4fluor)17]galantide and galanin(1-13)-[phenylalanine(4fluor)7]
      scyliorhinin-I are < 1. Hill's coefficients for galanin(1-13)-[norleucine10]
      scyliorhinin-I(3-10); galanin(1-14)-[alpha-aminobutyric acid8]-scyliorhinin-I;
      galanin(1-14)-[alpha-aminobutyric acid8, norleucine10]-scyliorhinin-I(3-10) are >
      1. A Hill's coefficient markedly different from 1 might indicate that an
      activation of more than one type of receptors, negative or positive receptor
      cooperativity or multiple-step agonist-receptor reaction.

PMID- 9149311
TI  - Effects of acute or chronic administration of risperidone on motor and sexual
      behavior of male rats.
AB  - A number of experiments were carried out to explore the behavioral profile of a
      novel antipsychotic, risperidone, after acute or chronic administration, in a
      dose range of 0.1-10 mg kg-1. This drug did not affect the acquisition and
      retention of avoidance behaviors in a dose of 0.1 mg kg-1, either after acute or
      chronic administration. Higher doses induced a inhibited acquisition and a
      facilitated extinction (only after chronic treatment) of active avoidance
      behavior, but no significant effect on the retention of passive avoidance
      responses. In contrast, haloperidol inhibited the acquisition and facilitated the
      extinction of active avoidance behavior, and reduced the retention of passive
      avoidance reaction at the dose of 0.1 mg kg-1 injected either acutely or
      chronically. Ambulation and rearing of rats rated in an open field was increased
      by risperidone injected acutely at the dose of 1 mg kg-1. Under the same
      experimental conditions, grooming appeared to be reduced. In the same test, acute
      or chronic haloperidol 1 or 10 mg kg-1 inhibited all behavioral items.
      Furthermore, in contrast to haloperidol, the acute or chronic administration of
      risperidone in a dose range of 0.1-10 mg kg-1 did not substantially induce
      catalepsy and did not affect apomorphine-induced stereotypies. Also, the dose of
      0.1 mg kg-1 induced a facilitation of male sexual behavior by increasing the
      frequency and reducing the latency of mountings, intromissions and ejaculations,
      while haloperidol 1 or 10 mg kg-1 inhibited this behavior. These findings suggest
      that the pharmacological profile of risperidone differs from that of classical
      neuroleptics, like haloperidol, probably due to different mechanism or site of
      action.

PMID- 9149312
TI  - Diazepam--its effects on the development of pentylenetetrazol kindling, related
      learning impairments, and neuronal cell loss.
AB  - Epileptics frequently experience cognitive disturbances. It was speculated that
      seizure activity causes neuronal cell loss which might, in part, contribute to
      these disturbances. To shed light on this problem, the kindling
      (pentylenetetrazol) model of epilepsy was used. Diazepam (DZP) was
      intraperitoneally injected (0.5 or 2.5 mg kg-1) in the course of kindling
      development. Six weeks after kindling completion the animals were tested for
      their performance in a shuttle-box and finally, the brains were processed for
      histological examination. It was found that DZP suppressed the expression of
      motor seizures. Kindled animals showed a significantly diminished shuttle-box
      performance. This impairment was not ameliorated by DZP. Moreover, the learning
      performance in control animals pretreated with DZP was low suggesting long
      lasting alterations due to DZP application. In kindled animals the number of
      neurones in the hippocampal CA1 region was significantly reduced and this effect
      was counteracted by the substance. The presented data suggest that seizure
      suppression and a reduction in neuronal cell loss must not automatically result
      in improved learning performance.

PMID- 9149313
TI  - Antidepressant treatment before hospitalization for major depression: often
      prescribed, often undertitrated.
AB  - Fifty-three patients hospitalised for major depression were given a semi
      structured interview to collect data allowing to consider the question of
      treatment in the period preceding hospitalisation. Twenty-one patients were
      discarded because they did not consult any physician (n = 5) or because they did
      it too late ( n = 11) or for they reached the threshold of major depression too
      late to allow sufficient time for efficacy of the treatment (n = 5). There
      remained a subsample of 20 potentially treatable patients. The majority of them
      refused their treatment (17%), were given no antidepressant treatment (14%) or at
      an insufficient dose (41%). If they received a sufficient dose, it was too lately
      (3%) or it was a maintenance therapy, which had not been modified in spite of a
      recurrence (14%), and finally only 10% of the potentially treatable patients
      could be considered as adequately treated, from a psychopharmacological point of
      view.

PMID- 9149314
TI  - Presentation and distribution of medicinal products after the new E.U. marketing
      procedures.
AB  - In this paper the new procedures for the marketing authorisation are considered
      from the point of the view of their influence on the medicinal product
      presentation (labelling and package leaflet), dispensing and distribution. The
      legal status of some active ingredients in different countries as well as the
      situation in the Italian domestic market have been analysed. Even if the European
      directive is completely implemented, the harmonisation process appears difficult
      in consideration of the different social, political and economical
      characteristics of the different countries, and is going to cover many years.

PMID- 9149315
TI  - Characterization of a peptide endothelium-derived constricting factor EDCF.
AB  - Endothelium regulates vascular tone by the release of dilator and constrictor
      mediators. Among the latter, besides endothelin, an 'endothelium derived
      constricting factor' EDCF sensitive to cyclooxygenase-inhibitors has been
      described. The aim of this study was to clarify the nature of this EDCF. Eluate
      from porcine aortic segments or supernatants (crude extracts) of porcine aortic
      segments were each tested for vascular effects in a bioassay system consisting of
      two endothelium-denuded acceptor vessels (rabbit abdominal aorta) before or after
      treatment with trypsin. The donor vessels were incubated with physiological
      saline solution with or without treatment with cycloheximide, quinacrine or
      indomethacine. Ultrafiltrates and fractions of a gelfiltration of the
      supernatants were also tested and compared with SDS-PAGE of these extracts.
      Finally, porcine aortic endothelial cells (PAEC) were cultured and the
      supernatant compared with that of the native aortae. A vasoconstrictive factor
      was released from the luminal surface of the porcine aortic segments, which if
      infused into the rabbit aortas induced two succeeding vasoconstrictions of 15-20
      min duration each (the first 20 min after the first of extract-infusion, the
      second after 50 min) reaching 7% amplitude of a 0.2 mumol 1(-1) norepinephrine
      induced constriction. These constrictions were enhanced if the crude extract of
      the porcine aortae was concentrated. This constricting factor was a protein with
      an approximative molecular weight of 9.000 Da. The release of this factor was
      insensitive to cycloheximide pretreatment indicating no de novo synthesis.
      However, the release of the factor could be markedly (50%) depressed by
      pretreatment with either quinacrine or indomethacine. The factor was not released
      from cultured PAEC. From these results, we conclude, that besides endothelin,
      endothelium luminally can release another endothelium-derived constricting factor
      named EDCF, a peptide with a molecular weight of 9.000 Da, which is not identical
      to endothelium and can induce long lasting vasoconstrictions. The release or
      synthesis of that EDCF seems to depend on cyclooxygenase and phospholipase A2
      activity. We, thus, propose the name PLA2-sensitive EDCF for that factor.

PMID- 9149316
TI  - Hemodynamic changes do not mediate the cardioprotection induced by the A1,
      adenosine receptor agonist CCPA in the rabbit.
AB  - Stimulation of adenosine A1 receptors is known to reduce infarct size in the
      rabbit heart. The aim of the present study was to verify whether a protective
      activity similar to that of the selective A1 receptor agonist, 2-chloro-N6
      cyclopentyladenosine (CCPA), could also be obtained by inducing comparable
      hemodynamic effects with drugs having different mechanisms of action. The effects
      of the beta-adrenoceptor blocker atenolol, the calcium channel blocker
      felodipine, the A2A-selective adenosine receptor agonist 2-hexynyl-5'-N-ethyl
      carboxamidoadenosine (2HE-NECA), and the non-selective adenosine receptor agonist
      5'-N-ethyl-carboxamidoadenosine (NECA) were tested. Groups of 12-15 anesthetized
      open-chest rabbits received a 5-min infusion of CCPA (50 micrograms kg-1 min-1),
      atenolol (1 mg kg-1 min-1), felodipine (50 micrograms kg-1 min-1), 2HE-NECA (1
      microgram kg-1 min-1), and NECA ( 1 microgram kg-1 min-1). Myocardial infarction
      was induced by a 30-min occlusion of a branch of the left coronary artery,
      followed by 3-h reperfusion. Infarct size was measured by tetrazolium staining.
      In controls, infarct size was about 40% of the zone at risk. Pretreatment with
      CCPA induced a marked decrease in heart rate (-40%) and blood pressure (-48%),
      and showed antiischemic activity (28% of the zone at risk). The other drugs
      tested produced similar effects on either heart rate (atenolol, -25%), or blood
      pressure (felodipine, 2HE-NECA and NECA, about -45%), but did not affect infarct
      size. IN this model, the reduction in infarct size by CCPA is most likely
      mediated by A1 receptors, since comparable hemodynamic effects, induced by other
      means, are not effective. A2A receptor stimulation does not appear to exert a
      protective effect.

PMID- 9149317
TI  - Cardioprotective effects of adenosine A1 and A2A receptor agonists in the
      isolated rat heart.
AB  - It has been postulated that the adenosine A1 receptor subtype, but also A2a
      receptors, are involved in mediating the beneficial properties of adenosine
      during ischemia and reperfusion. We investigated the effects of the selective A1
      adenosine receptor agonist, 2-chloro-N6-cyclopentyladenosine (CCPA), the
      selective A2A adenosine receptor agonists, 2-[p-(2-carboxyethyl)phenetylamino]-5'
      N-ethylcarboxamidoadenosine (CGS 21680), 2-hexynyl-5'-N-ethylcarboxamidoadenosine
      (2HE-NECA), and the non selective agonist, 5'-N-ethylcarboxamidoadenosine (NECA),
      on ischemia-reperfusion injury in Langendorff-perfused rat hearts. Global
      ischemia was induced for 15 min in paced hearts followed by 60 min reperfusion.
      Control hearts developed left ventricular dysfunction, as indicated by the
      increase in end diastolic pressure to 40.8 +/- 5.1 vs 5.9 +/- 1.0 mm Hg baseline,
      and in coronary perfusion pressure to 57.6 +/- 8.4 vs 28.8 +/- 2.2 mm Hg before
      ischemia. After 15 min of reperfusion, ventricular function (LVDP) recovered by
      83%, but creatine kinase levels were still significantly increased (294 +/- 55
      IUl(-1) vs basal), indicating the occurrence of myocardial injury. All adenosine
      agonists added to the perfusion medium 15 min prior to ischemia exerted
      protective effects against myocardial dysfunction and reperfusion injury. Thus,
      2HE-NECA (100 nM), CGS 21680 (10 nM), CCPA (3 nM) and NECA (100 nM) significantly
      (P < 0.05) decreased end diastolic pressure by 50-75% as compared with the
      control group. Similarly, all compounds significantly (P < 0.05) reduced coronary
      perfusion pressure by 30-45% vs control. For all drugs, recovery of LVDP occurred
      immediately after restoration of coronary flow. At 15-min reperfusion the
      adenosine agonists decreased myocardial creatine kinase release by 80-95% (P <
      0.05 vs control). These findings indicate that both A1 and A2A adenosine
      receptors are involved in protecting the myocardium against ischemia and
      reperfusion in isolated rat heart, even if through different mechanisms.

PMID- 9149318
TI  - Evaluation of the anti-oedematous effects of some H1-receptor antagonists and
      methysergide in rats.
AB  - A combined method was used for a comparative study of some H1 and H2 antagonists
      and methysergide. In male rats of the Wistar strain weighing 130 +/- 5 g, oedema
      was induced in the hind paw by the subplantar injection of zymosan, and
      simultaneously in the ear by the application of croton oil to the inner surface
      of the ear. Intraperitoneally orally administered H1 antagonists (dimethindene,
      clemastine, cyproheptadine, astemizole, cetirizine, loratadine and terfenadine)
      inhibited the oedema to a statistically significant extent, in a dose-dependent
      manner. Outstanding inhibition was observed after simultaneous administration of
      the antiserotonin methysergide with dimethindene, clemastine, loratadine or
      cetirizine.

PMID- 9149319
TI  - Structure-activity of three phospholipid analogues towards inhibition of
      phospholipase A2 in macrophages.
AB  - At concentrations 1-20 microns in culture medium of rat peritoneal macrophages
      which were stimulated with ionophore A23187, the phospholipid analogues 1-decyl-2
      octyl-glycerophosphocholine and 1-dodecyl-2-octanamido-2-deoxy
      glycerophosphocholine were found more potent inhibitors than 1-octyl-2-deoxy
      glycerophosphocholine to lower the phospholipase A2 activities. The inhibitory
      effect was measured by [3H] eicosatetraenoic acid ([3H]20:4) release in
      macrophages and extracellular fluids and synthesis of [3H] eicosanoids after
      incubation of macrophages with traces of the molecular species of lecithin 1
      octadecanoyl-2-[3H] eicosatetraenoyl glycerophosphocholine. The three
      phospholipid analogues developed higher inhibitory effects than mepacrine,
      dexamethasone or bromophenacyl bromide, at corresponding concentrations in
      medium.

PMID- 9149320
TI  - Chloroquine is a potent inhibitor of glutamate dehydrogenase in liver and kidney
      cortex of rabbit.
AB  - The effect of chloroquine and other antimalarial drugs on glutamate dehydrogenase
      activity was studied in liver and renal mitochondria as well as in kidney-cortex
      tubules of rabbit. In permeabilized mitochondria, with free access of substrates
      and drugs to glutamate dehydrogenase, 100 microns chloroquine decreased both
      glutamate synthesis and glutamate deamination by about 70 and 50%, respectively.
      Ki value was equal to 49 microns in both liver and renal mitochondria. Other
      antimalarials (amodiaquine, quinacrine, chinidine and chinine) showed much
      smaller effect on the enzyme activity. Both ADP and L-leucine, allosteric
      activators of glutamate dehydrogenase, did not abolish the inhibitory action of
      chloroquine. Moreover, when added at 200 microns concentrations all drugs besides
      chinine suppressed glutamate formation in kidney-cortex tubules while chloroquine
      and quinacrine inhibited also glutamate deamination. Furthermore, chloroquine at
      500 microns concentration decreased significantly [14C]glutamate transport into
      kidney-cortex mitochondria. In view of these observations it seems likely that
      chloroquine and some other antimalarials may inhibit the rate of glutamate
      metabolism in both liver and kidney-cortex causing hepatoxicity and
      nephrotoxicity. A possible action of chloroquine as an inhibitor of glutamate
      dehydrogenase in Plasmodium falciparum during the clinical treatment of malaria
      is discussed.

PMID- 9149321
TI  - Structure of a variable number tandem repeat of the serotonin transporter gene
      and association with affective disorder.
AB  - We have recently reported an association between a polymorphism of a variable
      number tandem repeat (VNTR) region of the serotonin transporter gene and
      susceptibility to major depressive disorder. We identified three alleles
      containing respectively 9 (STin2.9), 10 (STin2.10) and 12 (STin2.12) copies of a
      repetitive element. We report here the sequences of the three alleles. The
      repetitive element conformed to the consensus sequence, GGCTGYGACCY(R)GRRTG,
      where Y = T/C, R = G/A, with loss of the 12th base pair in one of the repeating
      elements. We have also extended the numbers of cases and controls in the study.
      The frequencies of the three alleles in 119 individuals with single or recurrent
      major depressive episodes, 128 individuals with bipolar disorder and a group of
      346 controls were compared. There was a significant difference between patients
      with affective disorder and controls in the proportion of individuals carrying
      the STin2.9 allele. For the risk of unipolar disorder given a single STin2.9
      allele, the odds ratio was 4.44 (95% Cl, 1.65-11.95) and for bipolar disorder
      3.22 (95% Cl, 1.15-9.09). The findings support the hypothesis that allelic
      variation in the serotonin transporter gene may contribute to susceptibility for
      both major depression and bipolar disorder.

PMID- 9149322
TI  - Neurotrophin-3 gene polymorphisms and schizophrenia: no evidence for linkage or
      association.
AB  - It has been suggested on the basis of neuropathological and epidemiological
      evidence that schizophrenia is, at least in part, a neurodevelopmental illness.
      Some patients show abnormalities in cell position in the medial temporal lobes of
      their brains. Neurotrophin-3 is one of many proteins essential for the proper
      growth and development of the nervous system. Therefore the finding of a
      polymorphism near the promoter region of the gene, alleles of which were
      associated with the disease, prompted us to attempt replication. In a linkage and
      association analysis of the same polymorphism using familial schizophrenics and
      population controls we found no evidence to support the finding. We conclude that
      mutations or polymorphisms at this gene are unlikely to be involved in the
      genetic aetiology of schizophrenia.

PMID- 9149323
TI  - Linkage analysis between schizophrenia and the Darier's disease region on 12q.
AB  - There have been reports of an association between Darier's disease, an autosomal
      dominant genodermatosis, and psychiatric illness. Recently the gene causing
      Darier's disease has been mapped to an area on 12q, between D12S58 and D12S84.
      The findings of linkage analysis of 4 markers in the Darier's disease region on
      12q in five families segregating schizophrenia are presented. They fail to
      support close linkage between schizophrenia and the Darier's disease region on
      12q.

PMID- 9149324
TI  - A PstI restriction fragment length polymorphism in the 5' untranslated region of
      DRD4 is not associated with schizophrenia.
AB  - We detected a PstI restriction fragment length polymorphism in the 5'-non-coding
      region of the dopamine D4 receptor gene (DRD4), making it the seventh known
      polymorphism for DRD4. DNA polymorphisms in the putative regulatory region of
      DRD4 are of interest because of the reported six-fold increase in D4 receptors in
      post-mortem schizophrenic brain tissue [Seeman P, Guan HC, Van Tol HHM (1993)
      Nature, 365, 441-445]. We found no difference in the PstI allele frequencies
      between DSM-III-R schizophrenia patients (0.76 and 0.24, n = 41), and matched
      control Caucasians (0.77 and 0.23, n = 46). The PstI DRD4 polymorphism has
      potential use in linkage and association studies with neuropsychiatric and
      cardiovascular disorders.

PMID- 9149325
TI  - Association study of bipolar disorder at the phospholipase A2 gene (PLA2A) in the
      Darier's disease (DAR) region of chromosome 12q23-q24.1.
AB  - We have previously described a pedigree in which affective disorder and Darier's
      disease cosegregate and, in an independent sample of 45 bipolar pedigrees,
      reported evidence in support of linkage between a putative susceptibility locus
      for bipolar disorder and markers in the Darier's disease region of chromosome
      12q23-q24.1. The maximum evidence for linkage was given by a polymorphism at the
      gene encoding secretory phospholipase A2 (PLA2A), a candidate gene for affective
      disorder. Dawson et al. (Psychiatric Genetics, 5, 177-180) recently reported
      allelic association with the same polymorphism at PLA2A in a sample of 54 bipolar
      probands and 56 controls. We have been unable to replicate the association in 127
      Caucasian British DSMIII-R bipolar probands and 223 Caucasian British controls.
      However, on the basis of several lines of evidence discussed in the paper, we
      believe that this genomic region in general, and the PLA2A gene in particular,
      are worthy of further study as candidates in the search for susceptibility genes
      for the functional psychoses.

PMID- 9149326
TI  - Recombination patterns around the breakpoints of a balanced 1;11 autosomal
      translocation associated with major mental illness.
AB  - The frequency and extent of pairing failure around human translocations are
      unknown. We have examined the pattern of recombination around the breakpoints of
      a balanced autosomal translocation t(1;11) (q43;q21) associated with major mental
      illness. DNA was available from 17 carriers and 10 non-translocation carriers
      with meioses involving four generations. The derivative 1 and 11 chromosomes were
      also isolated in somatic cell hybrids and used to confirm phase. We have
      genotyped pedigree members using 20 polymorphic markers within 10 cM on either
      side of both chromosome 1 and 11 breakpoints. We find no significant reduction of
      recombination in the vicinity of either breakpoint. However we estimate that
      there are insufficient meioses even in this large family to make a meaningful
      interpretation and suggest that sperm typing alone can answer these interesting
      questions.

PMID- 9149327
TI  - No association between particular DRD3 and DAT gene polymorphisms and manic
      depressive illness in a Spanish sample.
AB  - We have carried out an association study of a polymorphism in the 3'UTR of the
      dopamine transporter gene (DAT) and a polymorphism in the coding region of the D3
      receptor gene (DRD3) in Spanish patients with manic depression and in controls.
      No significant differences in allelic and genotypic frequencies of either of
      these polymorphisms was found in patients compared with controls.

PMID- 9149328
TI  - Association study between bipolar disorder and candidate genes involved in
      dopamine-serotonin metabolism and GABAergic neurotransmission: a preliminary
      report.

PMID- 9149329
TI  - Lower serum dipeptidyl peptidase IV activity in treatment resistant major
      depression: relationships with immune-inflammatory markers.
AB  - Previous research in this laboratory has shown that major depression is
      accompanied by decreased serum activity of dipeptidyl peptidase IV (DPP IV), a
      serine protease that cleaves N terminal dipeptides from peptides with penultimate
      proline or alanine. DPP IV is involved in the metabolism of peptides, T cell
      activation and proliferation, including the production of cytokines, such as
      interleukin-1 (IL-1) and IL-2. The aim of this study was to examine (i) serum DPP
      IV activity in major and treatment resistant depression (TRD) in relation to
      other established immune and inflammatory markers of that illness, and (ii) the
      effects of antidepressive treatment on DPP IV activity. Serum DPP IV activity was
      significantly lower in major depression and TRD than in normal controls. In
      normal and major depressed subjects, there were significant and positive
      relationships between serum DPP IV activity and total serum protein, serum
      albumin, zinc, iron and transferrin. In the group of depressed subjects, there
      were significant and positive relationships between serum DPP IV activity and
      number of CD4+T cells and CD4+/CD8+ T cell ratio. There were no significant
      effects of subchronic treatment with antidepressants on serum DPP IV activity.
      The findings suggest that: (i) lower serum DPP activity may occur in chronic
      depression, TRD as well as in the acute phase of major depression; (ii) lower
      serum DPP IV accompanies the 'chronic' acute phase response in depression; and
      (iii) serum DPP IV activity is tightly coupled to increased number of CD4+ T
      cells in depressed subjects, but not in normal controls. Our results do not
      exclude the possible effects of longer-term treatment with antidepressants on
      serum DPP-IV activity.

PMID- 9149330
TI  - Differences between morning and afternoon hormonal responses to D-fenfluramine in
      healthy humans.
AB  - The prolactin (PRL) and cortisol responses to oral D-fenfluramine (30 mg) and
      placebo were measured in seven healthy subjects (two women and five men) in the
      morning and in the afternoon. As compared to placebo, D-fenfluramine
      significantly increased plasma PRL levels in both the morning and the afternoon,
      with no significant circadian difference. On the contrary, D-fenfluramine
      significantly enhanced plasma cortisol levels in the afternoon, but not in the
      morning. These data suggest that the time of the day at which the D-fenfluramine
      challenge test is carried out may be an important variable in determining the
      glucocorticoid response to the 5-HT releasing agent in humans.

PMID- 9149331
TI  - Individual differences in the diurnal cycle of cortisol.
AB  - This study investigated individual differences in the diurnal cycle of cortisol
      and explored their relation to several psychosocial variables and to upper
      respiratory symptoms. Cortisol and daily experience were assessed for 2 days in
      109 healthy employed and unemployed community residents (mean age = 36.4 +/-
      12.1, 69% female); self-report upper respiratory illness (URI) symptoms were
      assessed for an additional 10 days. Fifty-six (51%) participants showed typical
      declines in cortisol during both days, 19 (17%) showed no significant diurnal
      pattern on both days, and 34 (31%) showed different diurnal patterns on the 2
      days. Individuals with no cycles did not differ from those with normal or
      inconsistent cycles on demographic factors, baseline psychological measures,
      health behaviors, or daily experiences over the two assessment days. Individuals
      without cortisol cycles, however, reported fewer URI symptoms than the remaining
      subjects. That 17% of our sample did not exhibit diurnal cycles of cortisol was
      surprising, given established views of normal endocrine function. Although
      average daily level of cortisol is related to a number of psychosocial and
      psychiatric factors (e.g. stress and depression), pattern of diurnal cycle was
      not related to any demographic or psychosocial measures in this study. The
      finding that flat cycles were related to fewer reports of URI symptoms suggests
      that perturbations in cycle may be related to processes associated with symptom
      susceptibility or symptom expression.

PMID- 9149332
TI  - Thyroid hormones correlate with symptoms of hyperactivity but not inattention in
      attention deficit hyperactivity disorder.
AB  - The diagnostic validity of dividing attention deficit hyperactivity disorder
      (ADHD) into two distinct subgroups, one with and one without hyperactivity, is
      controversial since there have been no physiological differences demonstrated
      between these two subgroups. In this study, the relationship between thyroid
      hormones and symptoms of hyperactivity was examined in subjects with resistance
      to thyroid hormone (RTH) and their unaffected family members. Clinical data were
      collected on 152 subjects; 75 subjects with RTH and 77 family members without
      RTH. Each subject was assessed using DSM-III-R criterion based, structured
      psychiatric interviews, and Total T3 (TT3), Total T4 (TT4) and TSH concentrations
      were measured. The total number of ADHD symptoms were assigned to either
      inattention or hyperactivity subgroups using DSM-III-R criteria. The total number
      of ADHD symptoms were then reassigned to inattention or hyperactivity/impulsivity
      subgroups using DSM-IV criteria. Pearson R correlation coefficients were
      calculated separately for the RTH and unaffected family members groups in order
      to determine the relationships between TSH, TT3 and TT4 concentrations, and the
      DSM-III-R and DSM-IV symptom categories of ADHD in both groups. TSH
      concentrations were not significantly correlated with any of the symptom
      categories in either group. However, in the RTH group, both TT3 and TT4
      concentrations were significantly and positively correlated with total symptoms
      of ADHD (DSM-III-R) as well as symptoms of inattention (DSM-III-R) and symptoms
      of hyperactivity (DSM-III-R). When DSM-IV criteria were used, which reassigns
      symptoms of impulsivity from the inattention to the hyperactivity category, only
      the positive correlation between TT3 and TT4 concentrations and symptoms of
      hyperactivity/impulsivity (DSM-IV) remained significant. In the group of
      unaffected family members, the relationship between TT3 concentrations and
      symptoms of hyperactivity/impulsivity (DSM-IV) was the only significant
      correlation. The data support the hypothesis that thyroid hormones may provide a
      physiological basis for the dichotomy between symptoms of inattention and
      symptoms of hyperactivity, particularly when DSM-IV criteria are applied.

PMID- 9149333
TI  - Menstrual variability and the measurement of menstrual synchrony.
AB  - While the timing of menstrual cycles must be modifiable in order for the
      phenomenon of menstrual synchrony to occur, cycle variability and the occurrence
      of irregularly long or short cycles complicate the measurement of the process of
      synchronization over time and of determining whether synchrony exists for women
      who have lived together for a long period of time. The paper examines how each of
      five different ways of measuring menstrual synchrony (utilized in the literature)
      deals with menstrual variability and irregular cycles. On the basis of this
      analysis, the mathematical concept of "the limit of a sequence,' and analysis of
      data according to these five different approaches, we recommend the approach in
      which women record their onset dates after they have been together for a
      prolonged period of time. The observed onset differences between the women are
      then compared to expected onset differences, based on the assumption of random
      onset occurrence. A significant influence of irregular cycle lengths on synchrony
      was not found in this data set and in the other studies which examined this
      issue. Research to date has focused on a relatively narrow aspect of menstrual
      regularity and synchrony and has failed to emphasize the coupled pattern of
      events over time as well as to analyze menstrual synchrony as a cyclic system.

PMID- 9149334
TI  - Differentiation of biliary epithelial cells from the mouse hepatic endodermal
      cells cultured in vitro.
AB  - Differentiation of biliary epithelial cells from hepatic endodermal cells of the
      mouse embryo was examined with a special attention to the role of the connective
      tissue. When the whole liver primordium of the 9.5-day mouse embryo was cultured
      in vitro for 5 days, the endodermal cells differentiated into mature hepatocytes
      expressing carbamoylphosphate synthetase I (CPSI) and accumulating glycogen.
      Intrahepatic bile duct cells and connective tissue were poorly developed in this
      culture. However, when the hepatic endoderm was recombined with the 4-day
      embryonic chick lung mesenchyme and cultured in vitro, the endodermal cells
      differentiated into many ductal epithelial cells as well as mature hepatocytes
      with abundant connective tissue development. These results suggest that the ducts
      might be bile ducts, and that connective tissue is very important for bile duct
      development. In addition, this in vitro culture system might be useful for the
      study of mechanisms of bile duct differentiation and congenital biliary atresia.

PMID- 9149335
TI  - Effects of cholestatic agents on the structure and function of bile canaliculi in
      neonatal rat hepatocytes in primary culture.
AB  - The effects of cytochalasin B and colchicine on the structure and function of
      bile canaliculi were studied in neonatal rat hepatocytes in primary culture.
      Cellular contacts of neonatal hepatocytes were not as tight as those of adult
      hepatocytes. There was no remarkable difference in the ultrastructure of bile
      canaliculi between neonatal and adult hepatocytes. Neonatal hepatocytes treated
      with cytochalasin B were round in shape and aggregated in groups of several
      cells. Actin filaments stained by rhodamine-phalloidin were disrupted and
      condensed at the cell periphery or around dilated bile canaliculi. Markedly
      dilated bile canaliculi with less microvilli were observed by transmission
      electron microscopy while the secretory function of horseradish peroxidase, which
      was used as a marker for uptake, transport and secretion into bile canaliculi,
      were maintained. The lumen of dilated bile canaliculi was found close to the
      undersurfaces of hepatocytes by scanning electron microscopy after turning over
      the cultured cells. By colchicine treatment, the filamentous structure of
      microtubules in neonatal hepatocytes disappeared. The ultrastructure of the bile
      canaliculi was not affected by the treatment, but transport and secretion of
      horseradish peroxidase into bile canaliculi were inhibited. The development of
      strict cellular polarity in neonatal hepatocytes may be suppressed in neonatal
      hepatocytes; however, cholestatic agents which rearrange the cytoskeleton caused
      the same morphological or functional changes of bile canaliculi as in adult
      hepatocytes.

PMID- 9149336
TI  - Normal and abnormal development of the human intrahepatic biliary system: a
      review.
AB  - Morphology and immunohistochemical features of the developmental process of the
      human intrahepatic biliary system (IBS) are reviewed. Human IBS arises from the
      ductal plate, a double-layered cylindrical structure located at the interface
      between portal mesenchyme and primitive hepatocytes. The ductal plate first
      appears from primitive hepatocytes (hepatoblasts) around 8 gestational weeks
      (GW), and its formation proceeds from the hepatic hilum to the periphery. The
      ductal plate gradually undergoes remodeling from 12 GW; some parts of the ductal
      plate disappear and other parts migrate into the portal mesenchyme. Around 20 GW,
      the migrated duct cells transform into immature bile ducts and peribiliary
      glands. Some immature peribiliary glands transform into pancreatic acinar cells
      around postnatal 3 months. The immature biliary elements express cytokeratins no.
      7, 8, 18 and 19. Several growth factors (TGF-alpha, HGF) and their receptors
      (EGFR, MET, ERBB2) were expressed in the primitive IBS cells. Some extracellular
      matrix proteins including type IV collagen, laminin and tenascin are expressed in
      the mesenchyme around the primitive IBS. During IBS remodeling, apoptosis and
      cell proliferation occur with appropriate expression of apoptosis-related
      proteins (bcl-2, Fas, c-myc, Lewis(y)). Some pancreatic digestive enzymes (alpha
      amylase, trypsinogen, lipase), cathepsin B, and matrix metalloproteinases (MMP-1,
      2, 3, 9) and their inhibitors (TIMP-1, 2) are expressed in the remodeling IBS
      cells. Glycoconjugate residues of glycoproteins gradually appear during IBS
      development. The appropriate expression of these immunophenotypes may play an
      important role in the normal development of IBS.

PMID- 9149337
TI  - Differential expression of the major histocompatibility antigens and ICAM-1 on
      bile duct epithelial cells in biliary atresia.
AB  - Aberrant expression on biliary epithelial cells of the major histocompatibility
      complex (MHC) antigens in association with adhesion molecule intercellular
      adhesion molecule-1 (ICAM-1) may be crucial to the immunopathogenesis of biliary
      atresia. The patterns of MHC class I and II expression in relation to ICAM-1
      expression as well as the associated lymphocyte subpopulations were studied in
      frozen section liver biopsies from six infants with biliary atresia. Intense ICAM
      1 expression was found on all ductal epithelial cells in association with MHC I.
      No ductal epithelial cells demonstrated MHC II expression. Lymphocyte populations
      within the portal tracts all expressed LFA-1 and were predominantly CD4 positive
      (> 70%). CD8 positive cells accounted for less than 30%. The expression of ICAM-1
      appears to be important in the pathogenesis of biliary atresia but is not linked
      to the expression of MHC II determinants. This result suggests that different
      regulatory mechanisms govern the expression of these important immunological
      receptors on biliary epithelial cells.

PMID- 9149338
TI  - Immunologic reaction and genetic factors in biliary atresia.
AB  - The characteristic histopathological features seen in the livers of patients with
      biliary atresia (BA) are very similar to those of primary biliary cirrhosis,
      which is an autoimmune disease. To clarify whether BA liver possess an
      immunological response similar to that in primary biliary cirrhosis, we studied
      HLA-DR expression in liver tissue of BA patients, using a HLA-DR staining method,
      and determined the frequency of HLA types in BA patients and their families. HLA
      DR was expressed by the bile duct epithelium in 11 of 16 liver specimens obtained
      from 13 BA patients. By contrast, HLA-DR was not expressed in liver specimens
      from 6 patients with congenital biliary dilatation. Among the HLA types seen in
      BA patients and their families, HLA-A33, -B44 and -DR6 were frequently expressed
      in blood. These results suggest that certain immunological factors and disease
      susceptible genes might be involved in the etiology of BA.

PMID- 9149339
TI  - Biliary, anorectal and esophageal atresia: a new entity?
AB  - A unique case of newborn biliary atresia associated with esophageal atresia and
      tracheoesophageal fistula, ano-rectal atresia, Reovirus type 3 infection and an
      early switch of fetal into adult hemoglobin is reported. At birth, the infant,
      who had only one umbilical artery, was operated on by primary anastomosis of the
      esophagous, and descending colostomy. At six weeks of age the baby underwent a
      "Kasai hepatic portoenterostomy-Type I" for a EHBA Type III, Subtype C2, Subgroup
      O ("aplasia" of all extrahepatic biliary ducts, including the gallbladder). The
      absence of an artery branch for the left lobe of the liver was observed.
      Histologically, the liver showed a hyperplasia of the intrahepatic bile ducts due
      to persistence of an excess of embryologic bile ducts in "ductal plate
      malformation" (DPM). Specific Reovirus type 3 antibodies were found in both the
      mother's and baby's sera. In the postoperative period the infant developed rapid
      and severe liver failure and underwent a successful liver transplantation.
      Although in most cases EHBA appears to be a perinatal event due to a necro
      inflammatory process of unknown etiology, cases associated with complex
      extrahepatic anomalies, may be due to different pathogenetic mechanisms supported
      by different causative agents operating very early in the fetal period. Viral
      infection seems to be the most reliable etiology.

PMID- 9149341
TI  - Endoscopic retrograde cholangiopancreatography (ERCP) in biliary tract disease of
      infants less than one year old.
AB  - We performed a total of 75 examinations with endoscopic retrograde
      chlangiopancreatography (ERCP) in 73 infants aged from 8 days to 300 days (mean
      71 days) between 1977 and 1995. ERCP examination was performed with a prototype
      duodenoscope and was successful in 47 of 52 examinations in biliary atresia, 9 of
      11 in neonatal hepatitis, all 4 in paucity of intra-hepatic bile duct, 4 of 5 in
      congenital biliary dilatation, 1 of 2 in duodenal stricture, and 1 case of in
      postoperative jaundice of hepatoblastoma. In 46 infants with biliary atresia,
      excluding one in whom the findings could not be evaluated due to poor x-ray image
      quality, we distinguished the following four patterns of ERCP findings: Pattern
      1, only the pancreatic duct could be demonstrated and no bile duct was visualized
      (76%); Pattern 2, only a part of the distal common bile duct with the pancreatic
      duct was visualized (2%); Pattern 3, the entire length of the common bile duct
      with the pancreatic duct was visualized without the gallbladder and the common
      hepatic duct (4%); and Pattern 4, the common bile duct and the gallbladder with
      the pancreatic duct were visualized without the common hepatic duct (18%). In all
      of these 46 patients, laparotomy, an operative cholangiogram, and histological
      evaluation of the biliary duct were performed. In 9 neonates with neonatal
      hepatitis, the biliary tract was opacified and biliary atresia was excluded.
      Laparotomy was thus avoided in these neonates. There was no complication caused
      by either ERCP or by anesthesia.

PMID- 9149340
TI  - Abnormal distribution of nerve fibers in the liver of biliary atresia.
AB  - We investigated changes in the pattern of hepatic innervation in liver specimens
      from 15 infants with biliary atresia and 4 age-matched controls by
      immunohistochemical methods. In the control, nerve fibers identified by
      immunoreactivity for neural cell adhesion molecule (NCAM) and S100 protein were
      present around the branches of hepatic arteries, portal veins and bile ducts in
      the portal areas and the hepatic lobules. In biliary atresia, NCAM and S100
      positive nerve fibers were increased in the vicinity of the hepatic arteries and
      the portal veins in the enlarged portal areas, while no nerve fibers were
      observed around bile ducts and periportal ductules which became NCAM positive. No
      innervation in the lobules was seen in any cases regardless of the histological
      alteration. These findings may suggest that the abnormal innervation in the liver
      with biliary atresia does not occur as a result of structural changes in liver
      architecture caused by portal fibrosis and inflammation, but is associated with
      immaturity or malformation of hepatic innervation in the patients.

PMID- 9149342
TI  - The treatment of biliary atresia in Europe 1969-1995.
AB  - European studies of biliary atresia have suggested that the aetiology is
      heterogeneous. Histological studies of the liver and biliary remnants excised at
      portoenterostomy have failed to identify any prognostic features except for the
      size of bile ductules in the porta hepatis. Most of the major series have
      confirmed that there is a relationship between age at portoenterostomy and
      clearance of jaundice which has been achieved in more than 67% of infants under
      10 weeks of age. Cholangitis reduced survival and bleeding from esophageal
      varices has occurred in more than 19% of long-term survivors. The 5-year jaundice
      free survival rate after portoenterostomy is 37% and the 10 year rate is 18%. It
      is predicted that these survival rates will improve. Orthotopic transplantation
      now results in long-term survival in 70% of patients who fail the
      portoenterostomy operation and long-term survival is now achieved in a majority
      of children born with biliary atresia.

PMID- 9149343
TI  - Japanese Biliary Atresia Registry, 1989 to 1994.
AB  - The Japanese Biliary Atresia Society founded in 1980 for the aim of
      investigations of all aspects of biliary atresia (BA), started a nationwide
      registry of BA patients in 1989. A total of 626 cases were registered from 1989
      to 1994. The male to female ratio was 0.58. Corrective surgery was performed in
      603 patients. Regarding the type of obstruction, 63 cases were Type I, atresia of
      the common bile duct, 9 were Type II, atresia of the hepatic ducts, and 543 were
      Type III, atresia of the porta hepatis. As initial corrective procedures,
      original Roux-en Y, Suruga II and Roux-en Y with intestinal valve were mainly
      employed. Jaundice cleared in 346 patients (57%) and decreased in 131, while it
      persisted in 120. The 5-year-follow-up showed that 34 patients, 49% of the
      patients who were followed up, were alive without jaundice, while 28 (41%) are
      dead. Thirty five, 33% of the patients who were entered to the Registry, were
      lost to follow-up.

PMID- 9149344
TI  - Determinants of life span after Kasai operation at the era of liver
      transplantation.
AB  - The aim of this work is to determine the influence of age, extrahepatic biliary
      lesions pattern (EHBP) and association to polysplenia syndrome (PS) on 10 years
      outcome of 164 patients with biliary atresia (BA) treated from 1984 to 1992 by
      initial Kasai operation (KO) and secondary liver transplantation (LT) when
      necessary. Actuarial crude survival without or after LT (CS), actuarial survival
      with native liver (NLS) and jaundice-free actuarial survival with native liver
      (JFS) were calculated from 1 to 10 years versus age (under/over 45 days), EHBP
      (favorable/ unfavorable) and PS (no/yes). Overall 10-year CS is 70%, overall 10
      year NLS and JFS are 14%. In univariate analysis, age at KO under 46 days,
      favorable EHBP (BA with patent gallbladder, and/or cystic dilatation of
      extrahepatic bile duct, or BA restricted to choledocus), and absence of PS are
      significant determinants of a better outcome regarding CS, NLS and JFS. EHBP is
      more discriminant than age. Influence of PS in this series is redundant with that
      of EHBP since 11/11 patients with PS had unfavorable EHBP.

PMID- 9149345
TI  - Treatment of biliary atresia by portoenterostomy and liver transplantation: The
      Queen Mary Hospital, Hong Kong experience.
AB  - Ninety three out of 96 patients with biliary atresia (BA) underwent Kasai 1
      portoenterostomy and 11 children subsequently underwent 12 liver transplantation
      (LTX) procedures which included 8 living related liver transplants (LRLT), 3
      reduced-size liver transplants (RSLT) and 1 orthotopic liver transplantation
      (OLT). During a follow-up period of 3-206 months (mean, 73 months) after
      portoenterostomy and 3-63 months after LTX, 50% of 96 patients are alive and well
      with total clearance of jaundice while 12% are mildly jaundiced, 10% are deeply
      jaundiced and 28% have died. Two of the 3 patients who did not undergo
      portoenterostomy and 25 from the portoenterostomy group have died. Of the latter
      group, 22 deaths occurred before, and 3 after the introduction of LTX therapy
      respectively. Of the 68 long-term survivors, 32 are less than 5, and 36 are 6-17
      years old. Complete clearance of jaundice was achieved in 55% of patients
      irrespective of whether portoenterostomy was initially performed at < 10 or
      between 10 and 12 weeks. Portoenterostomy performed beyond 13 weeks was
      associated with declining results. We conclude that (1) portoenterostomy combined
      with liver transplantation, when indicated, has given patients with BA a much
      better prognosis and (2) pediatric LTX in our institute is a well established
      procedure with 100% patient and 88% primary graft survival.

PMID- 9149346
TI  - Liver transplantation for extra hepatic biliary atresia.
AB  - Kasai portoenterostomy has transformed the prognosis for children with Extra
      Hepatic Biliary Atresia (EHBA). However, for children developing end stage liver
      disease following portoenterostomy, liver transplantation (OLT) is the treatment
      of choice. Between February 1989 and March 1996, 64 children with EHBA underwent
      79 transplants (26 males, 38 females; median age 2.2 years, range 5 months-17
      years; median weight 11.4 kg, range 5-65 kg). Of these, 58 (85%) had undergone
      previous portoenterostomy. Nineteen patients (30%) had gastrointestinal bleeding
      prior to OLT assessment. Mean serum bilirubin was 229 mumol/liter (range 11-801
      muml/liter). Four children had associated polysplenia syndrome. Of the 79
      transplants, 30 received whole and 41 reduced-size cadaveric grafts and 9 living
      related grafts. Eleven patients (17%) died, nine within one month of surgery.
      Thirteen patients were retransplanted once and one twice. There were 16 vascular
      complications (10 hepatic artery thrombosis, 3 portal vein thrombosis, 3 venous
      outflow obstruction) and 10 biliary complications (4 anastomotic leaks, 6
      strictures). Ten patients (16%) had bowel perforation following the transplant.
      The 5 year actuarial patient and graft survival for this group is 84% and 69%
      respectively with normal physical and mental development in the majority. OLT
      provides satisfactory treatment for children with EHBA with end stage liver
      disease with long term survival in the majority.

PMID- 9149347
TI  - Urgent liver transplantation for biliary atresia: the experience in Bicetre.
AB  - According to French rules for cadaver organ sharing, children with biliary
      atresia (BA) complicated with acute necrosis (ALN) can be registered on the
      waiting list for liver transplantation (LT) in a special intermediate grade
      urgent code. Over a 7 years period, 100 children have been submitted to elective
      LT for BA and 15 to urgent LT. Urgent procedures accounted for 25% of LT for BA
      in patients aged 0-2 years and 67% (8/12) in patients under 1 year of age.
      Children actuarial survival at 1, 12 and 48 months was respectively 66%, 60% and
      60% versus 92%, 86% and 85%, deaths occurring earlier in the urgent group. Graft
      actuarial survival at 1, 12 and 48 months were 60%, 53% and 53% versus 85%, 77%
      and 76% (p < 0.05), respectively. Outcome of children and grafts after LT is not
      significantly different in BA cases and in other urgent indications, excluding
      retransplantations. In a LT program based on cadaver organ donation, allocation
      of in an urgent registration code to children with BA and ALN offers them more
      than 50% chance to escape death and does not result in wasting of grafts.

PMID- 9149348
TI  - Living related partial liver transplantation in biliary atresia: 11 cases of
      experience.
AB  - Eleven children, 4 males and 7 females, with biliary atresia receiving living
      related liver graft were studied. The mean age was 1.8 years and the mean body
      weight was 10.3 kg. The donors were 4 fathers and 7 mothers. The graft was the
      lateral segment or left lobe. ABO blood group matching was compatible in 9 and
      incompatible in 2. All patients except one were crossmatch negative.
      Immunosuppression at induction was triple therapy (cyclosporine, azathioprine and
      steroid) or FK506 plus steroid. Acute rejection episodes were treated with pulse
      steroids. When the signs of rejection persisted despite steroid pulse therapy, 15
      deoxyspergualin (DSG) was added. The survival rate of the patients was 73%. Three
      patients died of portal vein thrombosis, hepatic artery thrombosis and sepsis
      respectively. Other major complications included hyperbilirubinemia, bile duct
      stenosis, bile leakage and portal vein anastomosis narrowing. Complications of
      the donor were sepsis in one, and liver dysfunction in two. Although there are
      some complications related to graft size mismatch and operative procedure, living
      related partial liver transplantation is an effective therapy in countries where
      donor source is restricted.

PMID- 9149349
TI  - Analysis of bilirubin fraction in the bile for early diagnosis of acute rejection
      in living related liver transplantation.
AB  - The diagnosis of acute rejection in liver transplantation usually needs hepatic
      biopsy, but hepatic biopsy sometimes involves severe complications. We analyzed
      biliary bilirubin fraction after living related liver transplantation by using
      high performance liquid chromatography (HPLC) and investigated availability for
      the early diagnosis of acute rejection retrospectively. Nine children with liver
      cirrhosis due to biliary atresia were included in this study, who underwent
      living related liver transplantation at The Second Department of Surgery, Tohoku
      University School of Medicine. Bile was collected daily from a biliary canulae
      inserted into the hepatic duct of the graft under aseptic and without exposure to
      the light. We measured the proportion of bilirubin diglucuronide (BDG), bilirubin
      monoglucuronide (BMG) and unconjugated bilirubin (UCB) of bile pigments in the
      bile by HPLC. In three of four patients with acute rejection, BDG + BMG (= Bc)
      was above 85% and BDG/Bc ratio was below 0.6 at the time of hepatic biopsy. After
      rejection therapy, BDG/Bc ratio increased in their bile. The remaining one case
      with acute rejection as well as bile duct injury due to arterial thrombosis of
      S2, Bc was below 85%, and BDG/Bc ratio was below 0.6. In four of the other five
      patients who had several severe complications, i.e., arterial or portal vein
      thrombosis, bile stasis due to cholangitis and sepsis due to necrotizing
      myofascitis, Bc was below 85% and BDG/Bc ratio was below 0.6. We concluded that
      analysis of biliary bilirubin fraction after liver transplantation could be
      reliable as a noninvasive maker and valuable for the early diagnosis of acute
      rejection.

PMID- 9149350
TI  - Biliary atresia: current management and outcome.
AB  - Between 1986 and 1994, 42 patients with BA were treated at the Kobe Children's
      Hospital. These patients underwent a wider excision of the hilar fibrous remnant
      with Roux-Y reconstruction (with or without intussuscepted valve) without stoma.
      Corticosteroids were used postoperatively when the stool was acholic or
      unsteadily cholic. The daily dose was reduced from 20 mg/day by half down. The
      patients were divided into two groups; in Group I (n = 17, before October 1990),
      a single course of corticosteroid therapy was employed. In Group II (n = 25, from
      November 1990 on), this regimen was repeated whenever the stool appeared less
      cholic. The bile flow improved significantly (excellent in 29% and 60%, and poor
      in 71% and 32% in Groups I and II, respectively.) Corticosteroids were used in 15
      Group I patients with good response in 10 and in 21 Group II patients, 15 of whom
      had multiple courses. Sixteen of the 21 Group II patients had a good response.
      The incidence of the cholangitis was not significantly different between the 19
      patients with valve and the 23 patients without valve. A 5 year survival
      significantly improved from 70% in Group I to 96% in Group II. In both groups,
      the survival rate significantly increased, when compared with the survival rate
      figured out with an assumption of OLT survivors as dead. On the same assumption,
      the survival rate of Group II is significantly more than that of the Group II.
      These suggest a positive contribution of liver transplantation and an aggressive
      corticosteroid therapy on better survival of Group II.

PMID- 9149351
TI  - A controlled trial of choleretic and hepatoprotective actions of Livzon and
      dehydrocholic acid in a model of obstructive jaundice in albino rats.
AB  - The authors have tried to examine the hepatoprotective and cholerectic action of
      a new indigenised drug, Livzon (Hind Chemicals Ltd., Kanpur, India) and compared
      its action to Decholin (casella-Riedel Pharma GmbH, Frankfurt, Germany), a known
      hepatoprotective and choleretic agent. Albino rats were chosen as the
      experimental animals. Obstructive jaundice was created by ligating the common
      bile ducts after taking liver biopsies. The animals were divided into three
      groups: (i) Control group-no drug was given, (ii) Livzon trial group, (iii)
      Decholin group. The animals were reoperated, liver biopsies were taken and
      histologically examined. The study confirmed the hepatoprotective and choleretic
      actions of Livzon and Decholin. However, Decholin was more of a choleretic, the
      Livzon was more hepatoprotective.

PMID- 9149352
TI  - Splenectomy in biliary atresia patients with recurrent jaundice following partial
      splenic embolization.
AB  - Splenectomy was performed for three patients with biliary atresia because of re
      exacerbation of their jaundice following treatment by partial splenic
      embolization (PSE). The subjects' red blood cell count and hemoglobin, serum
      level of hepatic enzymes (glutamic oxaloacetic transaminase, glutamic pyruvic
      transaminase, gamma-glutamyl transpeptidase, alkaline phosphatase, and lactic
      dehydrogenase), and total bilirubin (TB) were evaluated both before and after
      splenectomy in order to analyze the effects of splenectomy on these patients. The
      TB decreased significantly within 3 months after splenectomy in all three
      patients (13.0 +/- 1.6 mg/100 ml to 5.4 +/- 0.3 mg/100 ml, p < 0.05). The red
      blood cell count and hemoglobin increased gradually. There was a statistically
      significant correlation between the TB and the red blood cell count, and/or
      concentration of hemoglobin. The hepatic enzymes after splenectomy were not
      significantly different from those before splenectomy. The change in TB following
      splenectomy was essentially similar to that following PSE. These results
      suggested that the postoperative improvement in jaundice following splenectomy
      may not be due to improved hepatic function but merely a reflection of decreased
      red blood cell turnover. Splenectomy is a useful palliative procedure for
      jaundice in patients with biliary atresia for whom PSE is no longer effective.

PMID- 9149353
TI  - Further observations on cystic dilatation of the intrahepatic biliary system in
      biliary atresia after hepatic portoenterostomy: report on 10 cases.
AB  - This is a report on ten patients with cystic dilatation of the intrahepatic
      biliary system (CDIB) after hepatic portoenterostomy. They were five girls and
      five boys and the diagnosis of CDIB was made at ages 6 months to 11 years (mean
      age: 2.8 +/- 3.3 years). Follow-up ranged from one month to 15 years (mean: 5.5
      +/- 4.9 years). In order to elucidate the factors which affect the clinical
      outcome of such patients, the types of CDIB (Type A: noncommunicating solitary
      cyst, Type B: communicating solitary cyst, Type C: multi-cystic dilatation),
      clinical symptoms at onset of CDIB and the method for the treatment were reviewed
      in relation to the outcome. For the purpose of understanding pathogenesis of
      CDIB, immunohistochemical study on hepatobiliary system was done with monoclonal
      antibody for cytokeratin. Outcome of the patients of Type C was poor, whereas the
      outcome of patients with type A and B was good. The outcome of preoperatively
      jaundiced patients was poor, but jaundice-free patients showed good outcome.
      Method of treatment was not related to the outcome. As epithelium of CDIB was
      positive for monoclonal antibody of cytokeratin, it was suspected that
      pathogenesis of CDIB might be related to peribiliary gland which originated from
      ductal plate.

PMID- 9149354
TI  - Changes of hepatic volume after successful Kasai operation.
AB  - The number of long term survivors who have undergone Kasai operation for biliary
      atresia is increasing, but some have a hepatic dysfunction likely to require
      liver transplantation in the near future. Hepatic volume possibly reflects whole
      liver function, and our objective was to assess the changes of hepatic volume
      after Kasai operation. Ten patients were studied. Ages ranged from 3 to 27 years.
      They underwent Kasai operation at ages ranging from 50 to 80 days. Liver areas
      (cm2) on CT images were measured with an image processing and analysis program
      (NIH Image 1.57). Hepatic volume (cm3) was calculated by summing up the areas of
      each image and multiplying by slice thickness (cm). After Kasai operation, the
      size of the liver increased to 1.7-1.9 times the standard volume, and then
      reduced to normal size around 5 years of age. In the teens, hepatic volume
      decreased below the standard volume. Segmental hypertrophy accompanying atrophy
      of other hepatic segments was observed in 9 out of 10 patients; right lobe
      hypertrophy: 6, medial segment: 2, and lateral segment: 1. Therefore, progressive
      hepatic atrophy begins in the teens, but is compensated for by segmental
      hypertrophy.

PMID- 9149355
TI  - MRI findings in the liver in biliary atresia patients after the Kasai operation.
AB  - To evaluate liver function in biliary atresia (BA) patients after the Kasai
      operation, magnetic resonance imaging (MRI) was carried out 28 times in 19 BA
      patients. Sixteen of these were divided into three groups on the basis of the
      serum level of total bilirubin (t-bil), glutamic pyruvic transaminase (GPT) and
      gamma-glutamyltransferase (gamma-GTP) in the postoperative follow-up period (2-11
      years). In group 1 (n = 7) the t-bil was continuously kept under 1 mg/100 ml. In
      group 2 (n = 4) the t-bil was continuously kept under 1 mg/100 ml, but GPT and
      gamma-GTP remained high (GPT > 100 IU/liter, gamma-GTP > 200 IU/ liter) for more
      than 2 years. In group 3 (n = 5) an increase in the t-bil level reappeared (1-2
      mg/100 ml; n = 4, > 2 mg/100 ml; n = 1). The differences between MRI finding in
      the 3 groups, and the correlation between MRI findings and laboratory data (t
      bil, cholinesterase; ChE, GPT and gamma-GTP), which were taken around the time of
      MRI examinations, were studied. The results were as follows: (1) All 19 patients
      had normal or high signal areas of various sizes on T1 weighted images (WI). (2)
      Eighteen of 19 patients had high signal areas of various sizes on T2 WI in the
      portal system areas and/or liver parenchyma, and these areas were enhanced by
      gadolinium-DTPA in about half of the patients. (3) Ten of 16 patients had
      atrophic change over one liver lobe. (4) MRI findings for group 1 and the other
      groups were significantly different, and MRI findings, except for atrophic
      change, were correlated with the increase or decrease in laboratory data taken
      around the time of MRI examinations (p < 0.05). These results indicate that a
      normal or high signal area on T1 WI shows functional tissue, and that a high
      signal area on T2 WI shows tissue damaged by inflammation and/or progressive
      fibrosis. MRI is useful for evaluating liver function, especially in terms of
      morphological features, in BA patients after the Kasai operation, and will be one
      method for establishing their prognosis.

PMID- 9149356
TI  - Clinical significance of 99mTc-DTPA galactosyl human serum albumin scintigram in
      follow-up after Kasai operation.
AB  - The scintigram using 99mTechnetium-DTPA galactosyl human serum albumin (99mTc
      GSA) which binds to asialoglycoprotein receptors on hepatocytes is a good index
      of hepatocyte function in various liver diseases in adult patients. In 43
      patients (4 months to 30 years old) who had undergone Kasai procedure, we
      performed 53 series of 99mTc-GSA scintigrams and checked the laboratory data of
      blood draw and the clinical status. The indices for blood clearance and liver
      accumulation were evaluated on the basis of the dynamic data after 99mTc-GSA
      injection. HH15 as an index of the blood clearance, and LHL15 as an index of the
      accumulation of the hepatocytes were calculated and the HH15/LHL15 ratio (H/L15)
      was examined. 99mTc-GSA scintigram correlated with liver function and clinical
      status. Our results revealed that 1) The deterioration of the liver functions and
      clinical status correlates proportionally with H/L15, 2) The results of 99m
      Technetium-GSA scintigram correlate with several liver function tests, especially
      direct bilirubin, albumin and choline esterase, 3) This scintigram is an useful
      index of clinical status and hepatic function as well as the change of the
      hepatic parenchymal reserve in BA patients, especially for the evaluation of
      liver transplantation.

PMID- 9149357
TI  - Bone mineral analysis in patients with biliary atresia after successful Kasai
      procedure.
AB  - Metabolism is probably disturbed in patients with abnormal liver function who
      have undergone a successful Kasai procedure. We examined bone mineral metabolism
      in patients who have successfully undergone Kasai procedure. Bone mineral
      metabolism was examined in 8 patients with biliary atresia after a successful
      Kasai procedure. Five patients were female and 3 were male. The ages at Kasai
      procedure ranged from 50 to 80 days, and the follow-up periods ranged from 3 to
      27 years after the operation. All patients eat a normal oral diet. We examined
      plasma levels of 25-OH-D3, 1, 25-(OH)2-D3, Ca and phosphorus (P). Bone mineral
      content of the lumbar spine (L2-L4) was assessed by dual energy x-ray
      absorptiometry (DEXA), and the data were expressed as a bone mineral density
      (BMD). Two patients showed abnormal levels on hepatic function tests. Plasma
      levels of 1, 25-(OH)2-D3, Ca, and P were normal in all patients. The level of 25
      OH-D3 was normal in 7 patients. BMD levels were normal in 6 patients, but low in
      2 who had undergone partial splenic embolization and splenectomy, respectively,
      due to hypersplenism. In long-term survivors of Kasai procedure, measurement of
      BMD may detect bone mineral deficiency earlier than measurements of serum levels
      of 25-OH-D, 1, 25-(OH)2-D, Ca and P.

PMID- 9149358
TI  - Assessment of nutritional status of postoperative patients with biliary atresia.
AB  - Some patients of biliary atresia (BA) suffer from chronic hepatic dysfunction
      and/or persistent jaundice. The adverse effects of chronic liver disease on
      nutrition and growth should be considered on BA patients. We studied 45 BA
      patients ranging in age from 0.5 to 38 years and divided them into 2 groups.
      Group A contains the patients whose total bilirubin > or = 2 mg/100 ml, and Group
      B contains the patients whose total bilirubin < 2 mg/100 ml. We measured height,
      weight, triceps skin fold (TSF), midarm circumference (MAC) and midarm muscle
      area (MAMA). Visceral protein kinetics was evaluated on the basis of serum
      albumin and prealbumin levels. Caloric and protein intake was calculated by
      collecting intake data for 3 days. The results of this study were; 1) The mean
      TSF in Group A (47th percentile) was not significantly different from that in
      Group B (53th percentile). 2) The mean MAMA was significantly lower (p < 0.01) in
      Group A (16.4th percentile) than in Group B (36.7th percentile) 3) The prealbumin
      level was significantly lower (p < 0.001) in Group A (mean 9.9 mg/100 ml) than in
      Group B (mean 18.8 mg/100 ml). The authors conclude that the evaluation of MAMA
      and prealbumin were very useful to characterize the low metabolic status of
      protein in the damaged liver. And repeated nutritional assessment was necessary
      to evaluate liver function and provide adequate nutrition in BA patients.

PMID- 9149359
TI  - Long-term survivors in biliary atresia--findings for a 20-year survival group.
AB  - Recently, there has been remarkable increase in the survival rate in cases of
      biliary atresia (BA). However, long-term survivors are as yet a small population.
      Of the total of 152 patients undergoing surgery for BA during the period from
      1969 to 1995 in our institution, 39 of them were operated on more than 20 years
      ago with follow up for all but one of these, who can no longer be accounted for.
      Six are still alive, 1 male, and 5 females, two cases being of type I BA, and the
      other 4 of type III and 1 is unaccounted for. The prognosis of these individuals
      was clinically evaluated. At the present time, none of them is receiving hospital
      care, but 3 have experienced sequelae. Two patients required partial splenic
      embolization (PSE), endoscopic infusion sclerotherapy (EIS), and/or
      gastroesophageal decongestion and splenectomy (Hassab's operation) (Hassab 1967)
      for hypersplenism and/or portal hypertension. The other has needed hospital care
      for recurrent cholangitis. Laboratory investigations revealed a serum total
      bilirubin (TB) of less than 1.0 mg/100 ml in 3 of the 5 patients for which
      samples could be obtained, between 1.0 and 2.0 mg/100 ml in 1, and in excess of
      this in the remaining case. The 1-alanine 2 oxoglutarate aminotransferase (ALT)
      level was within the normal range in only 1, and was mildly to moderately
      elevated in 4. The white blood cell count (WBC) was less than 3,000/microliter
      and the platelet count was less than 10 x 10(4)/microliter in 1, and within the
      normal ranges in the other 4 patients. The results thus indicate that occult and
      progressive liver damage may occur in long-term survivors of BA.

PMID- 9149360
TI  - The outcome of surgery for biliary atresia and the current status of long-term
      survivors.
AB  - Between 1953 and 1995, 300 patients with biliary atresia underwent surgery at
      Tohoku University Hospital. The 10-year survival of patients who were operated on
      in or before 1965 was 9%. But the survival rate went up to 61% in patients
      operated on between 1976 and 1985. Eighty-five patients including 2 who developed
      liver failure after Kasai operation and underwent liver transplantation have
      survived more than 10 years. Eleven of them (13%) have recurrent or persistent
      jaundice. Of the 30 patients who have survived more than 20 years (10 males and
      20 females, age range; 20 to 41 years), 20 underwent hepatic portoenterostomy, 8
      underwent hepaticoenterostomy and the remaining 2 underwent hepatic
      portocholecystostomy. None of these patients has undergone liver transplantation.
      Twenty-two patients have led near-normal lives. The remaining 8 patients have
      experienced some troubles due to cholangitis, portal hypertension, intrahepatic
      gallstones and so on. Two of them are considered as candidates for liver
      transplantation. While the majority of long-term survivors of biliary atresia
      have good quality of life, close long-term follow-up is essential even in
      patients with biliary atresia aged 20 years or more.

PMID- 9149361
TI  - Dynamics of intramammary infection in the sheep caused by coagulase-negative
      staphylococci and its influence on udder tissue and milk composition.
AB  - Over an entire lactation 891 milk samples were collected from 99 ewes in a well
      managed dairy flock. Coagulase-negative staphylococci were isolated from 53 (5.9
      per cent) of the samples, with 13 (6.6 per cent) of the glands giving coagulase
      negative staphylococci in two or more consecutive samples. When a somatic cell
      count threshold of 6 x 10(5)/ml of milk was adopted as an indication of
      inflammation, 30 of the milk samples collected during early and mid-lactation,
      which contained coagulase-negative staphylococci, were considered to come from
      glands suffering subclinical mastitis. In five glands subclinical mastitis
      persisted for the entire lactation. A comparison of somatic cell counts measured
      with the fossomatic or Coulter counters suggested that the former gave the most
      reliable values, particularly in late lactation. After the experimental infection
      of 20 glands of meat breeds with coagulase-negative staphylococci, five glands
      remained infected for all 49 days of observation and seven glands excreted
      bacteria intermittently. Irrespective of the presence of coagulase-negative
      staphylococci in the sample, the composition of the milk from the challenged
      glands was significantly modified (P < 0.0001 for the infected, and P < 0.01 for
      the uninfected glands). Fat and protein concentrations were increased and lactose
      decreased, suggesting that although coagulase-negative staphylococci could not
      always be isolated, they persisted in many of the challenged glands and continued
      to influence the physiology of the gland. This possibility was supported by the
      presence of severe damage to the udder tissue of glands in which bacteria had
      been shown to be present for long periods.

PMID- 9149362
TI  - Corynebacterium pseudotuberculosis infection in Israeli cattle: clinical and
      epidemiological studies.
AB  - Morbidity due to Corynebacterium pseudotuberculosis infection occurred in 29
      dairy herds in Israel during 1989 to 1995. The disease occurred sporadically in
      17 of the herds with a morbidity of up to 5 per cent, and was epidemic in 12,
      with a morbidity of 5 to 35 per cent. Cutaneous abscesses were diagnosed in 609
      animals. Young cattle appeared to be less susceptible to the disease than older
      cows. Beef cattle herds were not affected. The disease appeared in the cutaneous
      form in 92.5 per cent of cases, the cutaneous and mastitic form in 5.9 per cent
      and the cutaneous and visceral form in 1.6 per cent. The cutaneous form appeared
      as deep subcutaneous abscesses on various parts of the body, with granulating
      ulcers exuding pus and blood. In 10 of the herds, C pseudotuberculosis was
      isolated from 33 mastitic cows which also had cutaneous lesions. The visceral
      form of the disease was detected when severely affected animals were slaughtered.
      In 23 of the herds, the disease occurred during the spring and summer dry season,
      from March to October; the highest prevalence was in the semi-arid Negev region.
      In 25 herds, the infection lasted for up to five months. The skin lesions on
      individual cows healed on average in 23.4 days, after either local or parenteral
      treatment. No significant difference was observed between the effect of systemic
      antibiotic treatment and local antiseptic treatment. One hundred and two (16.7
      per cent) severely affected animals were culled. There was a decrease in milk
      production and large increases in somatic cell counts in the 12 herds in which
      the disease was epidemic. None of the strains of isolated C pseudotuberculosis
      reduced nitrate.

PMID- 9149363
TI  - Outbreak of cryptosporidiosis in dairy goats in Brazil.
AB  - An outbreak of cryptosporidiosis is reported among 22 suckling kids aged one to
      two weeks which were maintained for experimental purposes at the veterinary
      hospital of the University of Minas Gerais. They were divided into three groups.
      Group A consisted of 10 animals with acute diarrhoea; initially their faeces were
      pasty but later they were excreted in watery streams. The animals were treated
      with gentamicin and fluid therapy but did not respond to treatment and died
      within a week. Postmortem examination revealed liquid intestinal contents,
      enlarged mesenteric lymph nodes, and hyperaemia and haemorrhage were observed in
      the final third of the small intestine of some of the animals. Of the 10 animals
      in group B four had diarrhoea and six were normal; postmortem examination showed
      that the macroscopic changes were similar to those observed in group A. Three of
      the animals with diarrhoea had a massive Cryptosporidium infection in the final
      third of the small intestine, caecum and colon. Four of the six normal animals
      had a moderate Cryptosporidium infection in the same organs. The two kids in
      group C died; they had pasty faeces, and there were many Cryptosporidium oocysts
      in the faecal smears.

PMID- 9149364
TI  - Influence of drench volume on the disposition of oxfendazole in sheep.

PMID- 9149365
TI  - Patent ductus arteriosus in an 11-month-old heifer.

PMID- 9149366
TI  - Electromyographic evaluation of a calf with white muscle disease.

PMID- 9149367
TI  - Qualifications in animal welfare science, ethics and law.

PMID- 9149369
TI  - Molasses toxicity in cattle.

PMID- 9149368
TI  - Analgesia in cats.

PMID- 9149370
TI  - Idiopathic tetanus in fattening cattle.

PMID- 9149371
TI  - Care of ferrets.

PMID- 9149373
TI  - Molecular modelling of cytochrome P4502D6 (CYP2D6) based on an alignment with
      CYP102: structural studies on specific CYP2D6 substrate metabolism.
AB  - 1. A molecular model of CYP2D6 has been constructed from the bacterial form
      CYP102 via a homology alignment between the CYP2D subfamily and CYP102 protein
      sequences. 2. A number of typical CYP2D6 substrates are shown to fit the putative
      active site of the enzyme, as can the specific inhibitor quinidine. 3. Some of
      the allelic variants in CYP2D6, which give rise to genetic polymorphisms in 2D6
      mediated metabolism, can be rationalized in terms of their position within the
      active site region. 4. The results of site-directed mutagenesis experiments are
      consistent with the CYP2D6 model generated from the CYP102 crystal structure. 5.
      The possibility of an alternative orientation within the active site may explain
      the CYP2D6-mediated metabolism of relatively large-sized substrates.

PMID- 9149374
TI  - Cytochrome P450 isoenzyme activities in cultured rat and mouse liver slices.
AB  - 1. The objective of this study was to determine the basal and inducible
      activities of several cytochrome P450 (CYP) isozymes and monitor the acinar and
      hepatocyte morphology in precision cut, cultured rat and mouse liver slices. 2.
      The slices were cultured up to 96 h in Chee's essential medium supplemented with
      insulin, transferrin, selenium, DMSO, dexamethasone and epidermal growth factor.
      A dynamic roller system was used to incubate the slices at 37 degrees C in an
      atmosphere of 95% O2:5% CO2. 3. Histopathology of the liver slices revealed
      maintenance of normal hepatic lobular architecture with time in culture. 4. CYP
      isozyme activities were measured at various times of culture. In rat liver
      slices, at 72 h, CYP1A1/1A2 activity was induced 4-fold by beta NF and 37-fold by
      dioxin (TCDD) whereas in mouse liver slices, 1A1/1A2 activity was not inducible
      by beta NF but was induced 19-fold by TCDD. At 72 h, CYP2A5 (coumarin-7
      hydroxylase) activity was not detected in rat liver slices but in mouse liver
      slices, 2A5 was induced 2-fold by beta NF, 11-fold by phenobarbital (PB) and 3
      fold by TCDD. 5. Hydroxylation of testosterone at specific positions was used as
      an indication of the activities of various P450 isoforms. Testosterone was added
      to the cultures at 0 and 72 h and the metabolites were measured at 24 and 96 h
      respectively by hplc analysis. Depending upon the species, the treatment and the
      time in culture, CYP1A, 2A, 3A, 2B and 2C activities were detectable. 3A activity
      was highly induced by PB in both rat and mouse liver slices. These results
      demonstrate that this culture system can be used to assess and compare xenobiotic
      metabolism in liver slices from rodent species.

PMID- 9149375
TI  - Extension of a predictive substrate model for human cytochrome P4502D6.
AB  - 1. Metoprolol, indoramine, codeine, tamoxifen and prodipine, compounds which are
      clinically used, and MDMA (ecstasy) were fitted in a small molecule model for
      substrates of human cytochrome P4502D6. 2. For both the R- and S-enantiomer of
      metoprolol, the R- and S-enantiomer of MDMA, and for indoramine and codeine (all
      proven substrates of cytochrome P4502D6) an acceptable fit in the substrate model
      was obtained. 3. For tamoxifen, for which the involvement of cytochrome P4502D6
      in the 4-hydroxylation is uncertain, no acceptable fit could be obtained in the
      substrate model. 4. For prodipine, a competitive inhibitor of P4502D6, for which
      the involvement of P4502D6 in the metabolism is uncertain, no acceptable fit in
      the substrate model could be obtained. 5. The substrate model was extended in a
      direction in which two large known substrates extend from the original substrate
      model. This extension did not change the flat hydrophobic region of the original
      substrate model.

PMID- 9149376
TI  - Assessment of rat liver slices as a suitable model system for studying the
      simultaneous sulphation and glucuronidation of phenolic xenobiotics.
AB  - 1. In most mammals, the xenobiotic 1-naphthol undergoes conjugation to produce
      predominantly the sulphate and glucuronide metabolites. 2. Using 1-naphthol, we
      established and validated rat liver slices as a model system to assess
      simultaneously the relative contributions of sulphation and glucuronidation to
      the metabolism of simple phenolic xenobiotics. 3. Determination of kinetic
      parameters for 1-naphthol sulphation showed identical affinity (Km approximately
      5 microM) in rat liver slices and in rat liver cytosol. 4. In liver slices, at
      low substrate concentrations (10 microM 1-naphthol), sulphation was the
      predominant pathway but was readily saturated, whereas at high concentrations of
      1-naphthol (100 microM) glucuronidation predominated. 5. In subcellular
      fractions, the Km for sulphation of 1-naphthol (5 microM) by liver cytosol was
      substantially lower than the Km for glucuronidation of 1-naphthol (48 microM) in
      liver microsomes, indicating saturation of sulphation by acceptor substrate was
      principally responsible for the shift towards glucuronidation at higher
      concentrations of 1-naphthol.

PMID- 9149378
TI  - Recognition of novel artifacts produced during the microsomal incubation of
      secondary alicyclic amines in the presence of cyanide.
AB  - 1. During the in vitro microsomal metabolism of the secondary alicyclic amines,
      nornicotine, anabasine or 4-benzylpiperidine in the presence of cyanide, a new
      product was formed. 2. Comparison of these new products with authentic compounds
      by hplc and ms showed they were the corresponding 1'-N-cyanomethyl compounds. 3.
      The source of the methylene group was shown to be formaldehyde, arising during
      incubation, from either microsomal lipid and/or glycerol used to store microsomes
      for long periods at low temperature. 4. The formation of the 1'-N-cyanomethyl
      compounds was enhanced in the presence of substrates producing formaldehyde
      during their metabolism, in direct relationship to the amount of formaldehyde
      generated. 5. The results indicate that care should be taken in interpreting data
      obtained from incubates containing secondary amines and cyanide, especially in
      the presence of substrates capable of donating formaldehyde.

PMID- 9149377
TI  - Major role of the CYP2C isozymes in deamination of amphetamine and benzphetamine:
      evidence for the quinidine-specific inhibition of the reactions catalysed by
      rabbit enzyme.
AB  - 1. The cytochrome P450 isozymes involved in the deamination of amphetamine (AP)
      and benzphetamine (BZP) have been studied in liver microsomes from rabbit and rat
      using isozyme-specific inhibitors. 2. Metabolism of BZP in rat yielding
      phenylacetone and formaldehyde was moderately inhibited by testosterone and
      chloramphenicol. N-Debenzylation was thought to be P450-dependent, but all
      inhibitors except for a non-specific inhibitor, SKF-525A, failed to inhibit this
      reaction. 3. In rabbit, quinidine and testosterone were potent inhibitors of both
      BZP deamination and dealkylation. Deamination of AP in rabbit was extensively
      inhibited only with quinidine. 4. AP deamination with purified rabbit CYP2C3,
      which was previously identified as the major isozyme responsible for this
      metabolism, was extensively inhibited with quinidine, previously thought to be a
      specific inhibitor of CYP2D. 5. These results strongly support the notion that
      the CYP2C isozymes play a major role in the deamination of both AP and BZP, but
      not for N-debenzylation of BZP in rat. However, on the basis of different
      sensitivities toward inhibitors, multiple isozymes seem to be involved in BZP
      deaminations in both species.

PMID- 9149380
TI  - Reinvestigation of a genetic-based classifier system: the effectiveness of
      recombination.
AB  - An empirical study for the effectiveness of recombination in a genetic-based
      classifier system applied to the field of ion chromatography is presented. From a
      comparison of the classifier system with and without crossover it followed that
      recombination was unable to make a significant contribution to the classification
      results. Despite this ineffectiveness, the genetic algorithm was a legitimate
      choice for solving the present classification problem because its population
      based properties were of greater importance than the issue of whether or not
      recombination significantly added to the performance. These findings prompt the
      testing of other classifier systems as well, in order to reveal the extent to
      which the presented results can be classified.

PMID- 9149381
TI  - Ion channels--analysis and simulation embedded in a flexible environment.
AB  - A collection of programs for ion-channel analysis is described. The package
      contains all standard routines for single-channel analysis and some routines for
      fluctuation analysis. Additionally, advanced algorithms for histogram building
      and filter correction are incorporated. The major advantage of this package is
      its embedding in the MATLAB environment, a general purpose program for huge
      numerical computations. Together with the ion-channel simulation facility this
      package forms the basis for optimizing analysis methods and readily incorporating
      new algorithms found in the literature.

PMID- 9149379
TI  - Effects of various pretreatments on the hepatotoxicity of inhaled styrene in the
      B6C3F1 mouse.
AB  - 1. The roles of cytochrome P450 monooxygenases (P450) and glutathione (GSH) in
      styrene hepatotoxicity were investigated in mice by pretreating with either
      phenobarbital (PB; P450 inducer), SKF 525A (P450 inhibitor), N-acetylcysteine
      (NAC; GSH precursor), or saline (vehicle control) prior to a 6-h exposure to
      either 500 ppm styrene on air. 2. Styrene caused hepatocellular degeneration or
      necrosis in all groups; these changes were more extensive and severe in mice
      pretreated with PB. Styrene significantly increased relative liver weights and
      serum ALT and SDH levels only in mice pretreated with PB. NAC did not prevent GSH
      depletion or hepatotoxicity. 3. In the fat of SKF 525A-pretreated mice a slight
      but statistically significant increase in styrene levels was observed, suggesting
      that metabolism was decreased; the SO/styrene ratio in the fat of PB-pretreated
      mice showed a slight, but statistically significant, increase indicating a slight
      increase in styrene metabolism. Neither SKF 525A nor PB caused changes in
      microsomal enzyme activity in vitro. 4. These results suggest that styrene may be
      activated by a pathway not totally dependent upon P450 enzyme activity, or more
      likely that PB and SKF 525A are not specific for the P450 enzymes involved in
      activation and detoxification of styrene.

PMID- 9149382
TI  - Freud's deshi: the coming of psychoanalysis to Japan.
AB  - This paper presents an account of four Japanese men, three of whom had an
      audience with Freud and who, with differing experiences and ambitions, returned
      to Japan to practice and develop psychoanalysis. Only two received any formal
      training, and two were strongly influenced by Buddhist thought. Freud gave no
      clear sign as to whom to appoint as leader, leaving the situation unsettled. This
      may have contributed to the continuing split and rivalry between groups, a split
      which was not resolved until the formation of the Japanese Psychoanalytic Society
      for trained analysts and the Association for interested laymen in the 1950s. From
      the beginning the development of psychoanalysis in Japan was informed by a
      paradox: the need to get Freud's approval and hence appear orthodox, while
      assimilating some of the concepts to the dictates of the culture.

PMID- 9149383
TI  - On the uses of history: the case of the Bell Curve.

PMID- 9149384
TI  - The Bell Curve and the shape of history.

PMID- 9149385
TI  - Heredity, intelligence and neuropsychology; or, why The Bell Curve is good
      science.

PMID- 9149386
TI  - Re-reconsidering Burt: beyond a reasonable doubt.
AB  - The Burt controversy has taken a number of strange twists and turns, leading many
      observers to conclude that he has been exonerated of the accusation that he
      fabricated his data on monozygotic twins reared apart. A comparison of his twin
      sample with that from other well documented studies, however, leaves little doubt
      that he committed fraud.

PMID- 9149387
TI  - The structures of triacylglycerols from sclerotia of the rye ergot Claviceps
      purpurea (Fries) Tul.
AB  - The triacylglycerol fraction of lipids extracted from sclerotia of the rye ergot
      Claviceps purpurea strain VKM F-2642D has been shown to comprise about 60% of the
      total lipids and to consist of at least seven constituents, namely, [R]-[R]-[R]
      (1.6% of the total fraction), [R-Ric]-[R]-[R] (27%), [R-Ric]-[R-Ric]-[R] (65%),
      [R-Ric]-[R-Ric]-[R-Ric] (4.8%), [R-Ric-Ric]-[R-Ric]-[R-Ric] (1.1%), [R-Ric-Ric]
      [R-Ric-Ric]-[R-Ric] (0.3%), and [R-Ric-Ric-Ric]-[R-Ric-Ric]-[R-Ric-Ric] (0.2%)
      (acyl residues at the 1(3), 2 and 3(1) positions of the glycerol moiety are
      indicated; R = nonhydroxylated fatty acid (C16, C18) residue, Ric = ricinoleyl
      residue). Non-hydroxylated fatty acyls (R) are n-16:0 (25-50% of the total), 16:1
      omega 7 (10-15%), n-18:0 (2-5%), 18:1 omega 9 (20-30%), and 18:2 omega 6,9 (10
      35%). The second and the third of the listed triacylglycerols are composed
      dominantly (by 86% or more) of 1,2-di-[R]-3-[R-Ric]-sn-glycerol and 1-[R]-2,3-di
      [R-Ric]-sn-glycerol, respectively.

PMID- 9149388
TI  - Synthesis and mass spectrometric characterization of digoxigenin and biotin
      labeled ganglioside GM1 and their uptake by and metabolism in cultured cells.
AB  - Selective acylation of mono-deacetyl lyso-GM1, i.e. beta-D-galactopyranosyl-(1-
      >3)-2-acetamido-2-deoxy-beta-D-galactopyr ano syl -(1-->4)-(alpha-D-neuraminyl-(2
      ->3))-beta-D-galactopyranosyl- (1-->4)-beta-D-glucopyranosyl-(1-->1)-(2S,3R,4E)-2
      amino-4-octa decen-1,3-diol, with N-succinimidyl-[1-14C]stearate afforded labeled
      mono-deacetyl GM1, i.e. beta-D-galactopyranosyl-(1-->3)-2-acetamido-2-deoxy-beta
      D-galactopyr ano syl- (1-->4)-(alpha-D-neuraminyl-(2-->3)-beta-D-galactopyranosyl
      (1-->4)-beta -D- glucopyranosyl-(1-->1)-(2S,3R,4E)-2-[1-14C]octadecanamido-4-
      octadecen-1, 3-diol, in good yield. Its condensation with either N-succinimidyl
      digoxigenyl-3-O-methyl carbonyl-epsilon-amino caproate or N-succinimidyl-D
      biotinyl-epsilon-aminocaproate led to radioactive GM1 derivatives carrying a tag
      for immuno-electron microscopy at the sialic acid residue. These GM1 derivatives
      could be hydrolyzed to the corresponding GM3 derivatives by treatment with GM1
      beta-galactosidase and beta-hexosaminidases. There was no further degradation by
      sialidases due to the bulky tag in the sialic acid residue. The uptake of biotin
      labeled GM1 by human skin fibroblasts, rat neuroblastoma cells B104 and human
      neuroblastoma cells SHSY5Y was 0.85, 0.58 and 1.62 nmol lipid/mg cellular
      protein, respectively, after an incubation for 66 h at 37 degrees C and was
      similar to that of untagged GM1. The uptake of digoxigenin labeled GM1 by these
      cell types was, however, significantly higher (3.1, 6.8, and 20.0 nmol lipid/mg
      cellular protein, respectively). Both the biotin and digoxigenin labeled GM1
      analogs were catabolized to the corresponding GM2 and GM3 derivatives in
      lysosomes of cultured cells. This demonstrates that these synthetic analogues are
      suitable for studying, by immuno-electron microscopy, their endocytosis and
      distribution in intralysosomal membranes.

PMID- 9149389
TI  - The enhancement by wortmannin of protein kinase C-dependent activation of
      phospholipase D in vascular endothelial cells.
AB  - Phosphatidic acid generation by phospholipase D (PLD) activation has been
      implicated in agonist- and oxidant-mediated endothelial cell signal transduction.
      We examined the effect of wortmannin on PLD activation in pulmonary artery
      endothelial and smooth muscle cells in culture. Pretreatment of bovine pulmonary
      artery endothelial cells (BPAECs) with wortmannin potentiated TPA- (100 nM), ATP-
      (100 microM), and bradykinin- (1 microM) induced [32P]PEt formation, an index of
      PLD activation. However, wortmannin by itself had no effect on PLD activity. The
      potentiating effect of wortmannin on TPA-induced PLD activation was dose- (1-10
      microM) and time-dependent (5-30 min) and was inhibited by bisindoylmalemide, an
      inhibitor of protein kinase C (PKC). Furthermore, down-regulation of PKC by
      prolonged treatment with TPA (100 nM, 18 h) attenuated the wortmannin effect.
      This effect of wortmannin was specific for TPA- or agonist-induced PLD activation
      as no potentiation of [32P]PEt formation was observed with H2O2 (1 mM) or
      ionomycin (1 microM). The effect of wortmannin was not due to activation of PKC
      alpha as determined by western blot analysis of PKC alpha in the cytosol and
      membrane fractions. Also, genistein, an inhibitor of tyrosine kinases, did not
      attenuate the wortmannin-mediated potentiation of PLD thereby suggesting non
      involvement of protein tyrosine phosphorylation. These results indicate that
      wortmannin potentiates PKC-dependent stimulation of PLD in vascular endothelial
      cells.

PMID- 9149390
TI  - Exogenously added alkylmethylglycerophosphocholine and
      alkylmethylcarbamylglycerophosphocholine accumulate in plasma membranes more than
      in intracellular membranes of rabbit platelets.
AB  - We found that extracellular addition of 2% bovine serum albumin (BSA) to a
      suspension of rabbit platelets after stimulation with platelet-activating factor
      resulted in a biphasic extraction of [3H]1-O-alkyl-2-O-methyl (or 2-O
      methylcarbamyl)-sn-glycero-3-phosphocholine. A fast phase of extraction of the
      phospholipid probe by BSA was found to be mainly due to removal of the probe
      remaining in an outer layer of platelet plasma membrane, whereas a second phase
      of extraction of the probe by BSA was mostly attributed to redistribution of the
      probe which had been flipped across the plasma membrane. On the basis of analysis
      of the biphasic extraction by BSA of 1-O-alkyl-2-O-methyl (or methylcarbamyl)-sn
      glycero-3-phosphocholine at various times after its addition, we suggested that
      the radioactive phospholipid accumulated in plasma membrane more than in
      intracellular membranes of rabbit platelets. In similar experiments with guinea
      pig polymorphonuclear leukocytes, we observed a monophasic extraction of 1-O
      alkyl-2-O-methyl (or methylcarbamyl)-sn-glycero-3-phosphocholine by BSA,
      indicating its unidirectional movement across the plasma membrane.

PMID- 9149391
TI  - A rainbow trout lectin with multimeric structure.
AB  - A novel lectin has been identified in rainbow trout serum and plasma. The lectin
      binds to Sepharose (an agarose polymer) in a calcium-dependent manner. Glucose, N
      acetyl-glucosamine, mannose, N-acetyl-mannosamine, L-fucose, maltose and alpha
      methyl-mannoside are good inhibitors of this binding, whereas glucosamine and D
      fucose inhibits to a lesser degree and mannosamine and galactose do not inhibit
      the binding to Sepharose. When analysed by SDS-PAGE under non-reducing
      conditions, the lectin appears as a characteristic ladder of bands with
      approximately 16 kDa between consecutive bands. Upon reduction, the lectin
      appears as a 16-kDa band. On size-exclusion chromatography of trout serum and
      plasma, the protein emerges over a broad range corresponding to sizes from about
      2000 kDa to less than 200 kDa. The NH2-terminal sequence (AAENRNQXPPG) shows no
      significant homology with known proteins. Because of the characteristic
      appearance in non-reducing SDS-PAGE and the lectin activity, we propose to name
      the protein "ladderlectin."

PMID- 9149392
TI  - Estrogen receptor is not primarily responsible for altered responsiveness of
      ovalbumin mRNA induction in the oviduct from genetically selected high- and low
      albumen chicken lines.
AB  - The role of estrogen receptor on ovalbumin mRNA induction by steroid hormones was
      investigated in primary cultures of oviduct cells from estrogen-stimulated
      immature chicks of genetically selected high- and low-albumen egg laying lines (H
      and L-lines). In experiment 1, the extent of ovalbumin mRNA induction and
      changes in estrogen and progesterone receptors were compared between the oviduct
      cells from H- and L-lines with or without steroid hormones in the culture medium.
      In experiment 2, the effect of estrogen receptor gene transfection on the
      induction of ovalbumin mRNA was studied in the oviduct cells from the L-line
      chicks. The results showed a close correlation of the changes in ovalbumin mRNA
      with the numbers of nuclear and total estrogen receptors in the oviduct cells but
      not with the numbers of nuclear and total progesterone receptors. Estrogen
      receptor gene transfection induced ovalbumin mRNA to a moderate extent in the
      absence of the steroid hormones. To our surprise, however, estrogen receptor gene
      transfection apparently suppressed the ovalbumin mRNA responsiveness to estrogen
      to a considerable extent. It was concluded, therefore, that the extent of
      estrogen receptor expression might not be primarily responsible for the
      differences in responsiveness to steroid hormones of oviduct cells from
      genetically selected H- and L-line chickens.

PMID- 9149393
TI  - Purification and characterization of class alpha and Mu glutathione S
      transferases from porcine liver.
AB  - Six cytosolic GSTs from porcine liver were purified by a combination of
      glutathione affinity chromatography and ion-exchange HPLC. The isoenzymes were
      characterized by SDS-PAGE, gel filtration, isoelectric focusing, immunoblotting
      analysis and determination of substrate specificities and inhibition
      characteristics. The purified GSTs belong to the alpha and mu classes,
      respectively. No class pi isoenzyme was isolated or detected. The class alpha GST
      pA1-1* exists as a homodimer (M(r) = 25.3 kDa), whereas GST pA2-3* consists of
      two subunits with different M(r) values (27.0 and 25.3 kDa). The estimated pI
      values were 9.5 and 8.8, respectively. Furthermore, four class mu porcine GSTs,
      pM1-1*, pM1-2*, pM3-?* and pM4-?*, were isolated. The isoenzyme pM1-1* possesses
      a relative molecular mass of 27.2 kDa and a pI value of 6.2. Additional pM1
      isoenzymes hybridize with the subunit pM2* (M(r) = 25.2) to furnish a
      heterodimer, which shows a pI value of 5.8. The other class mu isoenzymes are
      heterodimers with pI values of 5.45 and 5.05. Substrate specificities and
      inhibition characteristics correlate very well with those of the corresponding
      human isoenzymes. The results are discussed with regard to the usefulness of
      porcine GSTs as an in vitro testing model.

PMID- 9149394
TI  - Ethanol alters brain phospholipid levels which correlate with altered brain
      morphology.
AB  - The effects of embryonic exposure on brain phospholipid levels were studied by
      injecting various concentrations of ethanol into fertile chicken eggs at 0 days
      of development. At 18 days of development, the levels of total phospholipids and
      various phospholipid classes were assayed in brain tissue and correlated to
      neuron densities within the cerebral hemispheres and the optic lobes. Although
      ethanol concentrations ranging from 0 to 3700 microns/Kg egg wt. failed to
      influence either total brain weight or total brain phospholipid levels, ethanol
      induced changes in the levels of individual phospholipid classes were observed.
      When injected with 7 microns of ethanol/Kg egg wt., a 2- to 3-fold increase in
      brain phosphatidylethanolamine (PE) levels were observed with reduced levels of
      brain phosphatidylcholine (PC) and brain sphingomyelin (SP). When injected with
      74 microns of ethanol/Kg egg wt., ethanol-induced increases in brain
      phosphatidylserine (PS) and PE were observed with ethanol-induced decreases in
      brain PC and SP. Cell fractionation studies demonstrated ethanol-induced
      increases in brain PE and PS and ethanol-induced decreases in brain PC and SP in
      nuclear, mitochondrial, and microsomal membranes. These ethanol-induced
      alterations in brain phospholipid profiles correlated with ethanol-induced
      reductions in neuron densities within the cerebral hemispheres and optic lobes.

PMID- 9149395
TI  - Cuticular extracts of five common mantids (Mantodea:Mantidae) of the eastern
      United States.
AB  - We undertook a preliminary investigation of the cuticular extracts of five common
      mantid species in the eastern United States: Tenodera sinensis (Saussure), T.
      angustipennis (Saussure) and Mantis religiosa (Linnaeus) introduced from the Old
      World and Stagmomantis carolina (Johannson) and Bruneria borealis (Scudder),
      which are New World species. The major components of these mixtures were normal
      alkanes, predominately hentriacontane, or in the case of the parthenogenic
      species B. borealis, tritriacontane. Tricontanal was detected in the extracts of
      all five species, and smaller amounts of other aldehydes and n-tricontanol were
      detected in some species. Complex mixtures of methyl and dimethylalkanes also
      were present in these extracts. The composition of the cuticular hydrocarbons of
      these mantids may be an adaptation for reduction of evaporative water loss in
      these insects that inhabit open fields.

PMID- 9149396
TI  - Structural determination of monosialyl trisaccharides obtained from caprine
      colostrum.
AB  - Acidic oligosaccharides were separated by dialysis, ion-exchange, preparative
      paper and gel chromatography from caprine colostrum. Four sialyl trisaccharides
      were characterized by 1H-NMR spectrometry as follows: alpha-N-acetylneuraminyl
      (2,6)-beta-D-galactopyranosyl-(1,4)-2-N-acetami do-2 -deoxy-D-glucopyranose
      (Neu5Ac alpha 2-6Gal beta 1-4GlcNAc), alpha-N-acetylneuraminyl-(2,3)-beta-D
      galactopyranosyl-(1,4)-D-glucopyra nose (Neu5Ac alpha 2-3Gal beta-1-4Glc), alpha
      N-acetylneuraminyl-(2,6)-beta-D-galactopyranosyl-(1,4)-D-glucopyra nose (Neu5Ac
      alpha 2-6Gal beta 1-4Glc) and alpha-N-glycolylneuraminyl-(2,6)-beta-D
      galactopyranosyl-(1,4)-D -glucopyranose (Neu5Gc alpha 2-6Gal beta 1-4Glc).

PMID- 9149397
TI  - Comparative biochemistry of a cytosolic artiodactyl glycosidase.
AB  - Artiodactyls possess abundant neutral glycosidase activity in liver, kidney and
      intestine. This enzyme is cytosolic and displays a more neutral pH optimum, more
      acidic isoelectric point and broader substrate range than the corresponding
      acidic beta-galactosidases. The neutral glycosidases were more thermolabile than
      the respective acidic beta-galactosidases and displayed a relative molecular mass
      approximating 60 kDa. This isozyme appeared to be a minor species in both rat and
      dog liver. The porcine enzyme was studied in more detail. Porcine neutral
      glycosidase activity was detected in 45-day gestational fetuses in both liver and
      kidney but not brain. Fetal kidney activities were about half those observed in
      adult kidney extracts. Porcine neutral glycosidase was immunologically distinct
      from acidic beta-galactosidase and was immunologically similar to the
      corresponding isozymes from deer, ovine and bovine liver. Porcine neutral
      glycosidase was moderately inhibited by D-galactonic acid gamma-lactone and
      strongly inhibited by D-gluconic acid delta-lactone; however, acidic beta
      galactosidase was not inhibited by the delta-lactone. Inhibition by the gamma
      lactone was competitive for both enzymes. 4-Methylumbelliferyl-beta-D
      galactoside,-glucoside and -xyloside competed for the same active site. A
      polymorphism for fast- and slow-migrating isozymes of porcine neutral glycosidase
      was observed, which appeared to be under genetic control.

PMID- 9149398
TI  - Vitellogenin titres in normal and accelerated maturation of gregarious-phase
      Schistocerca gregaria.
AB  - Isolation of vitellogenin of the Schistocerca gregaria (Forskal) in its
      gregarious phase was achieved by a combination of gel permeation and anion
      exchange chromatography. Staining for carbohydrate and lipid moieties showed that
      the vitellogenin is a glycolipoprotein. The vitellogenin of S. gregaria has a
      native molecular weight of about 700 kDa. On SDS-PAGE, the protein showed nine
      apoproteins of about 124, 120, 105, 60, 59, 58, 57, 53 and 34 kD. Determination
      of the levels of vitellogenin by ELISA in the haemolymph of maturing females
      showed that those exposed to mature males from 1 to 2 days after ecdysis had
      increased levels of vitellogenin from day 10 (81.1 +/- 4.5). In contrast, females
      exposed to immature males or kept alone showed an increase (107.3 +/- 0.9 and
      70.2 +/- 2.7) not until day 16 or later, respectively. These results are
      consistent with the accelerating effect of pheromonal emissions from mature males
      on the maturation of female S. gregaria.

PMID- 9149399
TI  - Purification and comparison of beta-1,3-glucan binding protein from white shrimp
      (Penaeus vannamei).
AB  - A beta-glucan binding protein (BGBP) was identified in both white (Penaeus
      vannamei) and blue shrimp (P. stylirostris) plasma. White shrimp BGBP was
      purified by affinity chromatography using immobilized laminarin, and its
      molecular and biological properties were described. White shrimp BGBP is a
      monomeric protein with a molecular mass of 100 kDa, similar to those described
      for other crustacean BGBPs. White and blue shrimp BGBPs can be detected with
      antisera against crayfish BGBP and brown shrimp BGBP. Both amino acid composition
      and N-terminal sequence are markedly similar to brown shrimp (P. californiensis)
      and crayfish (Pacifastacus leniusculus) BGBP, indicating that this recognition
      protein is present in freshwater and marine crustaceans.

PMID- 9149400
TI  - Purification and characterisation of hepatic glutathione transferases from a
      herbivorous marsupial, the brushtail possum (Trichosurus vulpecula).
AB  - A single glutathione transferase isoenzyme was purified from hepatic cytosol of
      the brushtail possum and shown to represent 3.6 +/- 0.3% of the total cytosolic
      protein. Characterisation of the enzyme, termed Possum GST 1-1, indicated that it
      possessed similar catalytic activity and structural homology with isoenzymes
      belonging to the alpha class of glutathione transferases. This homodimeric GST
      exhibited a single band with an apparent molecular mass of 25.4 kDa on sodium
      dodecyl sulphate-polyacrylamide gels and an apparent pI of 9.8. Inhibition
      studies demonstrated that Possum GST 1-1 displays binding affinity for a range of
      inhibitors similar to that shown by alpha class GSTs purified from other mammals.
      Immunoblot analysis demonstrated immuno-cross reactivity between Possum GST 1-1
      and antisera raised against human alpha GST, while this GST did not cross-react
      with antisera raised against human mu and pi GST. N-terminal sequencing of
      purified Possum GST 1-1 revealed that the N-terminus of the protein is chemically
      blocked. Sequence analysis of three internal peptide sequences demonstrated
      homology with mammalian alpha GSTs. Of particular interest is the significant
      substrate specificity that Possum GST 1-1 displays with both organic and
      inorganic hydroperoxides. It is proposed that this substrate specificity is an
      evolutionary adaptation to a diet high in potentially toxic plant
      allelochemicals.

PMID- 9149401
TI  - Chicken insulin-like growth factor binding protein (IGFBP)-5: conservation of
      IGFBP-5 structure and expression during evolution.
AB  - A complementary DNA (cDNA) clone encoding chicken insulin-like growth factor
      binding protein-5 (cIGFBP-5) was isolated. The nucleotide sequence of the 1236-bp
      clone encodes a mature polypeptide of 251 amino acids with a calculated molecular
      weight of approximately 28.2 kDa. The deduced amino acid sequence is 83%
      identical to human IGFBP-5. Labeled cIGFBP-5 cDNA detected a single mRNA
      transcript of approximately 6 kb by Northern blot analysis of various tissues
      obtained from embryonic and 6 weeks post-hatch chickens; interestingly, adult
      heart showed an approximately 10-fold increase in cIGFBP-5 mRNA relative to
      embryonic heart. The pattern of IGFBP-5 mRNA expression in chicken tissues was
      similar to that found in mammals during fetal and extrauterine life. In addition,
      IGFBP-5 mRNA was abundant in primary cultures of chicken myoblasts throughout in
      vitro differentiation and fusion. The conservation of IGFBP-5 primary structure
      and expression pattern across vertebrate species suggests conservation of
      important functions during evolution, particularly in muscle differentiation.

PMID- 9149403
TI  - Changes in the resistive and reactive components of abdominal impedance during
      the 1-21 day post-mortem periods in rats.
AB  - The magnitudes of the resistive (R) and reactive (X) components of total
      abdominal impedance (Zt) at 10 kHz, and of transcellular impedance (Zi),
      cytoplasmic impedance (Ri) and cell membrane capacitance (C), were calculated
      from sequential measurements of Zt, phase angle (theta) and extracellular
      impedance (Ze), in each of eight rat cadavers maintained at 9.0 +/- 1.5 degrees
      C. Total impedance, theta, R, X, Ze and Ri increased during the first 3 days of
      death, while C decreased. Thereafter, each of these parameters decreased with
      increasing post-mortem interval. The data indicate that Zt was predominantly
      resistive, and that Zt became progressively more resistive, and less reactive,
      with increasing time since death. Transcellular impedance remained relatively
      constant during the first 9 days, prior to increasing to more than 160% of its
      initial (3 h) value at 21 days post-mortem. This change coincided temporally
      with, and was attributable to, a time-dependent decrease in cell membrane
      capacitance post-mortem. Further studies, using human post-mortem tissues or body
      segments, will determine whether or not time-related changes in one or more of
      the impedance parameters may be used to estimate post-mortem interval.

PMID- 9149402
TI  - Molecular cloning, characterization and expression of a nitric oxide synthase
      from porcine pulmonary artery endothelial cells.
AB  - The lack of sequence information and clones of porcine pulmonary artery
      endothelial cell (PAEC) constitutive nitric oxide synthase (ecNOS) cDNA limits
      comparative analysis between porcine and human PAEC. Therefore, we cloned,
      characterized and expressed the ecNOS cDNA from porcine PAEC. Two oligonucleotide
      primers were designed based on the published human ecNOS cDNA sequence and used
      to clone porcine PAEC ecNOS using 5' and 3' rapid amplification of cDNA ends
      reverse transcriptase polymerase chain reaction technique. A full-length ecNOS
      cDNA was cloned and sequenced, representing a protein of 1205 amino acids with a
      molecular mass of 134 kDa. A mammalian expression vector (pcDNA3) containing this
      cDNA was transfected into COS-7 cells, and ecNOS activity was detected by
      monitoring the formation of [3H]-citrulline from [3H]-L-arginine. Expression of
      ecNOS activity was predominantly associated (> 90%) with the total membrane
      fraction of these transfected cells. The deduced amino acid sequence of porcine
      ecNOS cDNA, containing binding sites for NADPH, flavin adenine dinucleotide and
      bound flavin mononucleotide, shows 94% identity to human ecNOS. The molecular
      weight of porcine ecNOS mRNA was estimated to be 4.7 kb by Northern blot
      analysis, similar to human ecNOS mRNA. This suggests that porcine ecNOS is
      similar to human ecNOS in deduced amino acid sequence and structure.

PMID- 9149404
TI  - Nitrogen levels in long bones from coffin burials interred for periods of 26-90
      years.
AB  - Samples of long bones were obtained from 42 bodies buried in coffins at two sites
      over a 26 to 93 year period. Quicklime had been added to 17 of the coffins and
      there was fuel oil contamination of three of these. Long bone total nitrogen
      levels obtained by the macro Kjeldahl method were subjected to statistical
      analysis and their distribution plotted on a graph of burial time versus bone
      total nitrogen content. The highest nitrogen level recorded was 4.06 g per 100 g
      of bone (26 years) and the lowest 3.27 g per 100 g of bone (80 years). The oldest
      burial (93 years) gave a total nitrogen level of 3.49 g per 100 g of bone. For
      practical purposes, for burials deeper than 4 ft, the rate at which nitrogen is
      lost is independent of depth of burial. Although the overall trend was for
      nitrogen content to decrease with age, it was noted that despite being the oldest
      of the burials, the quicklime burials still possessed a relatively high nitrogen
      content. The maintenance of a relatively high nitrogen content in the quicklime
      burials was thought at first to be due to the quicklime acting as an inhibitor of
      decomposition during the initial period of interment. Statistical analysis,
      however, showed there to be no correlation between the addition of lime and the
      bone nitrogen level. Fuel oil contamination of three of the skeletons led to a
      high nitrogen content being recorded in the long bones, giving the impression
      that those burials were more recent than they actually were.

PMID- 9149405
TI  - Multiplexing of Y chromosome specific STRs and performance for mixed samples.
AB  - A combination of four Y-specific polymorphic STR loci was amplified
      simultaneously using fluorescently labeled primers. Multiplex conditions required
      optimization to eliminate constant bands and amplification products for female
      DNA. A series of experiments was carried out for mixtures of DNA from two males,
      and from male and female individuals for the Y-specific STRs and an autosomal
      locus. For the male/male mixtures amplified with the Y specific system, and
      amplified for an autosomal locus, the minor component in the mixture could only
      be identified up to a ratio of 1:10, 1:50 respectively. In male/female DNA
      mixtures the Y STR alleles could be identified for the highest ratio tested, 400
      pg male in DNA in 800 ng female DNA which amounts to a ratio of 1:2000.

PMID- 9149406
TI  - Distribution of HLA-DQA1 alleles in Arab and Pakistani individuals from Dubai,
      United Arab Emirates.
AB  - PCR-based typing of the HLA-DQA1 locus, using allele specific oligonucleotide
      (ASO) probes and reverse dot blot methodology was used to determine allelic
      distributions and construct a database for Arab and Pakistani individuals living
      in Dubai. Genotype and allelic frequencies were calculated, and the data were
      tested for departures from Hardy-Weinberg (HWE) equilibrium. The most frequent
      HLA-DQA1 alleles among Dubaian Arabs are DQA1 4 and 1.2. Among Pakistanis, the
      most frequent allele is also DQA1 4. No significant deviations from HWE were
      detected.

PMID- 9149407
TI  - Multiplex amplification of STR loci with gender alleles using infrared
      fluorescence detection.
AB  - The analysis of short tandem repeat (STR) polymorphisms has proven extremely
      useful for gene mapping, paternity testing, and forensic analysis. Several
      commercial products are currently available for performing amplification and
      analysis of STRs. We have adapted Promega Geneprint Systems for use with a high
      sensitivity infrared (IR) fluorescent automated DNA sequencer. IR-labeled
      amplification products are generated by including a small quantity of IR-labeled
      dATP in the reaction. Several Geneprint STR loci can be multiplexed together with
      the amelogenin sex identification locus in a single amplification reaction. We
      have successfully amplified up to five Geneprint STR loci together with the
      amelogenin locus thus improving the throughput of analysis. Purified genomic DNA
      as well as simulated forensic samples have been utilized for these multiplex
      amplifications.

PMID- 9149408
TI  - The role of carbohydrates in biologically active natural products.

PMID- 9149409
TI  - The biosynthesis of C5-C25 terpenoid compounds.

PMID- 9149410
TI  - Diterpenoid and steroidal alkaloids.

PMID- 9149411
TI  - Lethal Giardia from a wild-caught sulphur-crested cockatoo (Cacatua galerita)
      established in vitro chronically infects mice.
AB  - An axenic culture of Giardia was established from a sample of infected intestine
      obtained following autopsy of a sulphur-crested cockatoo (Cacatua galerita). The
      cockatoo recently captured in the wild and with good muscle tone died along with
      several other cage mates, apparently of an overwhelming, acute infection of
      Giardia. Trophozoites which established in the traditional, axenic Giardia medium
      (TYI-S-33 with supplementary bile) were morphologically identical to G.
      duodenalis. When outbred Quackenbush Swiss neonatal mice were infected with
      trophozoites a chronic infection was established and parasites were still present
      at 38 days post-inoculation. Weight gain by infected mice was reduced by 20%,
      thus mimicking failure-to-thrive syndrome in children, and maximum parasite load
      was more than 3-fold higher in comparison with other G. duodenalis strains.
      Analysis of the electrophoretic karyotype, rDNA and hybridization studies
      together with Giemsa- and trichrome-stained samples, and scanning electron
      microscopy indicated that the bird-derived Giardia belonged to the duodenalis
      group. This is the first report of infection of mammals with Giardia isolated
      from a bird. These data may have potentially serious implications for
      contamination of watersheds and establishment of zoonotic infections.

PMID- 9149412
TI  - The histones of Plasmodium falciparum: identification, purification and a
      possible role in the pathology of malaria.
AB  - A quick and simple method of purifying the histones from Plasmodium falciparum
      culture supernatant or from infected erythrocytes is described. The proteins were
      present only in preparations rich in P. falciparum nuclear material and were
      soluble at acid pH and in strongly anionic detergents. Four proteins, of 14-18
      kDa were identified as the P. falciparum core histones. N-terminal sequence
      analysis of the 16 and 18 kDa proteins and of a tryptic fragment of the protein
      mixture revealed strong homologies with deduced cDNA or protein sequences of
      histones H2A, H2B, and H3 of P. falciparum and other species. Antibodies raised
      against the proteins cross-reacted weakly with histones of other species and, on
      immunofluorescence, localized the proteins to schizont nuclei. Anti-P. falciparum
      histone antibodies were detected in sera of semi-immune human adults but these
      antibodies did not react with human histones on a Western blot. The large
      quantities of P. falciparum histone released and the chronic nature of malarial
      infection, together with the unusually high avidity of histones for ligands found
      in renal and vascular basement membrane, raise the question of a role for
      histones in the pathogenesis of malarial infection. We suggest that histones or
      histone-antibody complexes may contribute to disease pathology.

PMID- 9149413
TI  - Enrichment and biochemical characterization of Toxoplasma gondii tachyzoite
      plasmalemma.
AB  - The protozoan parasite Toxoplasma gondii possesses a triple surface membrane
      called the pellicle. This is made of an outer plasmalemma and an inner membrane
      complex lying under the plasmalemma. Using a high salt glycerol treatment
      followed by sonication, we have obtained a partial dissociation of the pellicle.
      A plasmalemma-enriched fraction was isolated on 0.7 M sucrose. It was identified
      by immunodetection of the tachyzoite major surface antigens. Protein content,
      resolved by SDS-PAGE, revealed that the surface protein SAG1 is the major
      component of the plasmalemma. The plasmalemma fraction is made of small vesicles
      (20-100 nm) which possess a low density (1.085-1.090 g/cm3 in sucrose)
      contrasting with other eukaryotic plasma membranes (1.12-1.16 g/cm3).

PMID- 9149414
TI  - Cloning of the entire COWP gene of Cryptosporidium parvum and ultrastructural
      localization of the protein during sexual parasite development.
AB  - Molecular cloning and immunoelectron microscopy have been used to clone the full
      length gene encoding Cryptosporidium parvum oocyst wall protein (COWP) and to
      analyse at the ultrastructural level the expression and localization of COWP
      during development in the gut. COWP is 1622 amino acids long, has a typical
      leader peptide and consists of 2 amino acidic domains each containing distinct
      repeated elements possibly originating from a common ancestral precursor.
      Electron microscopy localized COWP in a large cytoplasmic inclusion and in the
      wall-forming bodies of early and late macrogametes, respectively. Ultrastructural
      analysis of double-walled sporulating and mature oocysts indicated that COWP is
      selectively localized in the inner layer of the oocyst wall. This study provides
      the first localization at the ultrastructural level of a cloned coccidian oocyst
      wall protein.

PMID- 9149415
TI  - Cloning, heterologous expression and antigenicity of a schistosome cercarial
      protease.
AB  - A gene coding for the 30 kDa Schistosoma mansoni cercarial protease was amplified
      using the polymerase chain reaction (PCR) from genomic DNA templates. Cloning and
      sequencing of several independent PCR clones revealed the presence of an intron
      additional to the one described in the original cloning of the gene. The 3 exons
      were cloned into expression vectors so that they could be expressed as separate
      glutathione-S-transferase (GST) translational fusions. Recombinant bacteria
      carrying these expression plasmids expressed the fusion proteins at high levels.
      Western blotting of bacterial lysates with sera raised against the native S.
      mansoni cercarial protease showed that all 3 exons were recognized. Thus we have
      produced recombinant bacteria capable of providing large amounts of an S. mansoni
      antigen for immunological studies and evaluation as a candidate vaccine.

PMID- 9149416
TI  - The effects of FaRPs on the motility of isolated muscle strips from the liver
      fluke, Fasciola hepatica.
AB  - The effects of a range of FMRFamide-related peptides (FaRPs) on isometric
      contractility were tested using isolated muscle strips from the liver fluke, F.
      hepatica. The neuropeptides tested were the molluscan FaRPs, FMRFamide and
      FLRFamide, the turbellarian FaRPs, RYIRFamide and GYIRFamide, the cestode
      peptides, NPF and GNFFRFamide, and the nematode FaRPs, AF-1 (KNEFIRFamide), AF-2
      (KHEYLRFamide), AF-8 (KSAYMRFamide), and PF-4 (KPNFIRFamide). Dose-response
      experiments were undertaken at a concentration range of 5 nM-5 microM for all of
      the neuropeptides tested. FMRFamide and AF-8 caused statistically significant
      increases in the amplitude and frequency of contractions at concentrations of 0.5
      microM and 5 microM. FLRFamide and AF-2 also caused significant increases in
      contraction frequency at concentrations of 0.5 microM and 5 microM, although a
      significant increase in amplitude of contraction was observed only at a
      concentration of 5 microM. GYIRFamide increased both amplitude and frequency
      significantly at concentrations of 50 nM, 0.5 microM and 5 microM. RYIRFamide
      significantly increased frequency of contractions at concentrations of 0.5 microM
      and 5 microM, but failed to have a significant effect on contraction amplitude.
      AF-1 at a concentration of 5 microM increased contraction amplitude, but failed
      to have an effect on frequency at any of the concentrations used. PF-4 caused a
      statistically significant increase in both the amplitude and frequency of
      contractions at a concentration of 5 microM. NPF and GNFFRFamide had no effect on
      the in vitro motility of F. hepatica over the range of concentrations tested. The
      results are discussed in the light of possible structure-activity relationships
      in the FaRPs tested.

PMID- 9149417
TI  - Comparative analysis of the distribution of bradykinin-, GYIRFamide- and
      neuropeptide F-like immunoreactivities in the monogenean, Diclidophora merlangi.
AB  - An indirect immunocytochemical technique combined with confocal scanning laser
      microscopy has been used to demonstrate immunoreactivities to the nonapeptide,
      RPPGFSPFR (bradykinin, BK) and the endogenous flatworm regulatory peptide,
      GYIRFamide in the nervous system of the monogenean, Diclidophora merlangi. In
      addition, a simultaneous double-labelling technique was employed to examine
      possible co-localization of GYIRFamide- and neuropeptide F (NPF)
      immunoreactivities, using antisera to the C-terminal nonapeptide-amide of NPF
      (Moniezia expansa, FAIIGRPRF. NH2). BK immunostaining was restricted to a small
      population of nerve cells and associated fibres within the ventral nerve cords
      and to 2 pairs of nerve cells innervating the cirrus and the pharynx,
      respectively. No immunopositive nerve cells and fibres were identified within the
      brain or in association with the female reproductive apparatus. In contrast,
      GYIRFamide staining was abundant throughout the central and peripheral nervous
      systems, and appeared similar to the staining pattern revealed using an FMRFamide
      antiserum. GYIRFamide immunoreactivity was localized to nerve cells and fibres
      within the paired cerebral ganglia and the longitudinal ventral, dorsal and
      lateral nerve cords and their numerous interconnecting transverse commissures.
      The plexuses of the buccal suckers, pharynx and clamps of the haptor were
      strongly immunopositive for GYIRFamide, as were nerve cells innervating the
      ootype, the oviduct and the vitelline reservoir of the reproductive apparatus.
      Double-labelling experiments indicated an apparent co-localization of GYIRFamide
      and NPF immunoreactivities.

PMID- 9149418
TI  - Effect of praziquantel and liposome-incorporated praziquantel on peritoneal
      macrophage activation in mice infected with Mesocestoides corti tetrathyridia
      (Cestoda).
AB  - The activation of peritoneal macrophage effector functions after therapy with
      free PZQ and PZQ incorporated in liposomes (lip.PZQ) was studied in the
      Mesocestoides corti-mouse model system. Each drug formulation was administered to
      an infected group of mice in 6 daily doses from day 14 p.i. Phagocytic activity
      of macrophages increased significantly after the administration of both drug
      formulations, more after lip.PZQ with an earlier peak observed for PZQ (day 3)
      than for lip.PZQ (day 6). Empty liposomes had no significant effect. The average
      counts of ingested particles in phagocytosing cells were significantly higher
      only after lip.PZQ administration. The pattern of changes in phagocytic activity
      correlated with the reduction of parasite numbers in the peritoneal cavity, with
      the highest observed on day 6 after therapy with lip.PZQ. Phagocytosis of lip.PZQ
      in vivo stimulated significantly the respiratory burst in peritoneal macrophages,
      with the highest concentration of superoxide anions recorded on day 1 after the
      last dose, whereas therapy with PZQ itself did not increase this process
      significantly. The capacity for the respiratory burst declined in all groups with
      progressing infection. It is proposed that the phagocytic activity of peritoneal
      macrophages after therapy was stimulated indirectly as a consequence of
      activation of the specific immune response. The larvicidal effect of lip.PZQ on
      the tetrathyridia in the peritoneal cavity was synergistic with the phagocytic
      activity and might be the result of double action of drug and superoxide anions
      generated during the respiratory burst stimulated by this drug formulation.

PMID- 9149419
TI  - Mechanisms of specificity of association between the nematode Steinernema
      scapterisci and its symbiotic bacterium.
AB  - We suggest a new mechanism for the maintenance of specificity of the association
      between the entomopathogenic nematode Steinernema scapterisci and its symbiotic
      bacteria. We evaluated the development and reproduction of infective and non
      infective juvenile S. scapterisci in monoxenic combinations with its symbiotic
      bacteria, Xenorhabdus sp. 'S' and with the bacterial symbiont of Steinernema
      carpocapsae and Steinernema riobravis. Although development of non-infective
      stages occurred on all Xenorhabdus spp., the development of infective juveniles
      to the 4th stage ('dauer' recovery) was significantly delayed and reduced with X.
      nematophilus and Xenorhabdus sp. 'R', the bacterial symbionts of S. carpocapsae
      and S. riobravis, respectively. 'Dauer' recovery improved significantly when the
      cultures of X. nematophilus and Xenorhabdus sp. 'R' were supplemented with cell
      free filtrates from Xenorhabdus sp. 'S'. The infective juvenile S. scapterisci
      produced in all 3 cultures were virulent to Galleria mellonella larvae,
      confirming successful retention of Xenorhabdus from other steinernematids in
      their intestine. In fact, S. scapterisci infective juveniles containing X.
      nematophilus or Xenorhabdus sp. 'R' were more virulent to G. mellonella than
      those containing their natural symbiont, Xenorhabdus sp. 'S'. We believe that
      this is the first demonstration of the symbiont-specific exit of infective
      juveniles from the 'dauer' phase which represents the finest level of specificity
      of bacteria-nematode association. This is also the first report of successful
      isolation of the natural symbiont of S. scapterisci.

PMID- 9149420
TI  - Neutral lipids and the assessment of infectivity in entomopathogenic nematodes:
      observations on four Steinernema species.
AB  - An 8-point visual index was developed for Oil Red O staining of neutral lipids in
      infective juveniles (IJs) of Steinernema carpocapsae (A11), S. riobravis (Biosys
      355), S. feltiae (UK76) and S. glaseri (NC). The visual index was found to be a
      reliable and rapid method for determining the relative neutral lipid content of
      individual IJs and was validated quantitatively by gas chromatography. The
      relationship between neutral lipid utilization and infectivity of IJs stored in
      distilled water at 25 degrees C was also investigated and the first quantitative
      results on neutral lipid utilization in entomopathogenic nematodes are reported.
      Neutral lipid contents of freshly harvested IJs of S. carpocapsae, S. riobravis.
      S. feltiae and S. glaseri were 31, 31, 24 and 26% dry wt, respectively.
      Steinernema carpocapsae showed a sigmoidal pattern for neutral lipid utilization
      while S. riobravis used neutral lipids at an almost constant rate. Survivorship
      of these two species ranged between 120 and 135 days, whereas S. feltiae and S.
      glaseri lived > 450 days and had a slower rate of lipid utilization during a 260
      day storage period. Oil Red O staining showed that individual IJs in each
      population utilized lipids at different rates, even though they had the same
      initial lipid index. The infectivity of S. riobravis, S. feltiae and S. glaseri
      declined with lipid utilization. In contrast, S. carpocapsae maintained a high
      level of infectivity even at relatively low lipid levels. Therefore, neutral
      lipid content was found to be a suitable indicator of infectivity for S.
      riobravis, S. feltiae and S. glaseri but not for S. carpocapsae.

PMID- 9149421
TI  - Genome sizes of the entomopathogenic nematodes Steinernema carpocapsae and
      Heterorhabditis bacteriophora (Nematoda:Rhabditida).
AB  - There is currently no information on the genome size and complexity in the
      entomoparasitic nematodes Steinernema and Heterorhabditis. DNA reassociation
      kinetics were used to determine the genome size and complexity in 2 species:
      Steinernema carpocapsae and Heterorhabditis bacteriophora. C0t curves derived
      from renaturation kinetics of denatured DNA indicate that the genomes of these
      entomoparasitic rhabditids are different both in size and complexity. Genome
      sizes were estimated at 2.3 x 10(8) bp for S. carpocapsae and 3.9 x 10(7) bp for
      H. bacteriophora and repetitive DNA contents were found to represent 39% and 51%
      of these respective genomes.

PMID- 9149422
TI  - Problems of reproducibility--does geologically ancient DNA survive in amber
      preserved insects?
AB  - Apparently ancient DNA has been reported from amber-preserved insects many
      millions of years old. Rigorous attempts to reproduce these DNA sequences from
      amber- and copal-preserved bees and flies have failed to detect any authentic
      ancient insect DNA. Lack of reproducibility suggests that DNA does not survive
      over millions of years even in amber, the most promising of fossil environments.

PMID- 9149423
TI  - Hemispheric specialization for global and local processing: the effect of
      stimulus category.
AB  - Neuropsychological evidence indicates that the global aspect of complex visual
      scenes is preferentially processed by the right hemisphere, and local aspects are
      preferentially processed by the left hemisphere. Using letter-based hierarchical
      stimuli (Navon figures), we recently demonstrated, in a directed-attention task,
      lateralized neural activity (assessed by positron emission tomography) in the
      left prestriate cortex during local processing, and in the right prestriate
      cortex during global processing. Furthermore, temporal-parietal cortex was
      critically activated bilaterally in a divided-attention task that involved
      varying the number of target switches between local and global levels of letter
      based hierarchical stimuli. Little is known about whether such stimulus
      categories influence such hemispheric lateralization. We now present data on
      brain activity, derived from positron emission tomography, in normal subjects
      scanned during either local or global processing of object-based hierarchical
      stimuli. We again observe attentional modulation of neural activity in prestriate
      cortex. There is now greater right-sided activation for local processing and
      greater left-sided activation for global processing, which is the opposite of
      that seen with letter-based stimuli. The results suggest that the relative
      differential hemispheric activations in the prestriate areas during global and
      local processing are modified by stimulus category.

PMID- 9149424
TI  - Pattern formation triggered by rare events: lessons from the spread of rabies.
AB  - Understanding of large-scale spatial pattern formation is a key to successful
      management in ecology and epidemiology. Neighbourhood interactions between local
      units are known to contribute to large-scale patterns, but how much do they
      contribute and what is the role of regional interactions caused by long-distance
      processes? How much long-distance dispersal do we need to explain the patterns
      that we observe in nature? There seems to be no way to answer these questions
      empirically. Therefore, we present a modelling approach that is a combination of
      a grid-based model describing local interactions and an individual-based model
      describing dispersal. Applying our approach to the spread of rabies, we show that
      in addition to local rabies dynamics, one long-distance infection per 14000 km2
      per year is sufficient to reproduce the wave-like spread of this disease. We
      conclude that even rare ecological events that couple local dynamics on a
      regional scale may have profound impacts on large-scale patterns and, in turn,
      dynamics. Furthermore, the following results emerge: (i) Both neighbourhood
      infection and long-distance infection are needed to generate the wave-like
      dispersal pattern of rabies; (ii) randomly walking rabid foxes are not sufficient
      to generate the wave pattern; and (iii) on a scale of less than 100 km x 100 km,
      temporal oscillations emerge that are independent from long-distance dispersal.

PMID- 9149425
TI  - Adaptive changes in Plasmodium transmission strategies following chloroquine
      chemotherapy.
AB  - Both theory and data suggest that malaria parasites divert resources from within
      host replication to the production of transmission stages (gametocytes) when
      conditions deteriorate. Increased investment into transmission stages should
      therefore follow subcurative treatment with antimalarial drugs, but relevant
      clinical studies necessarily lack adequate control groups. We therefore carried
      out controlled experiments to test this hypothesis, using a rodent malaria
      (Plasmodium chabaudi) model. Infections treated with a subcurative dose of the
      antimalarial chloroquine showed an earlier peak and a greater rate of gametocyte
      production relative to untreated controls. These alterations led to correlated
      changes in infectivity to mosquitoes, with the consequence that chloroquine
      treatment had no effect on the proportion of mosquitoes infected. Treatment of
      human malaria commonly does not result in complete parasite clearance. If
      surviving parasites produce compensatory increases in their rate of gametocyte
      production similar to those reported here, such treatment may have minimal effect
      on decreasing, and may actually increase, transmission. Importantly, if increased
      investment in transmission is a generalized stress response, the effect might be
      observed following a variety of antimalarial treatments, including other drugs
      and potential vaccines. Similar parasite life history counter-adaptations to
      intervention strategies are likely to occur in many disease-causing organisms.

PMID- 9149426
TI  - The biochemical basis of synaptic plasticity and neurocomputation: a new theory.
AB  - The recent finding that dendritic spines (on which 90% of all excitatory synapses
      on pyramidal cells are formed) are not permanent structures but are continually
      being formed and adsorbed has implications for the present theoretical basis of
      neurocomputation, which is largely based on the concept of fixed nerve nets. This
      evidence would tend to support the recent theories of Edelman, Freeman, Globus,
      Pribram and others that neuronal networks in the brain operate mainly as
      nonlinear dynamic, chaotic systems. This paper presents a hypothesis of a
      possible neurochemical mechanism underlying this synaptic plasticity based on
      reactive oxygen species and toxic 0-semiquinones derived from catecholamines (i)
      by the enzyme prostaglandin H synthetase induced by glutamatergic NMDA receptor
      activation and (ii) by reactive nitrogen species derived from nitric oxide in a
      low ascorbate environment. A key factor in this neuromodulation may be the fact
      that catecholamines are potent antioxidants and free radical scavengers and are
      thus able to affect the redox mediated balance at the glutamate receptors between
      synapse formation and synapse removal that may be a key factor in
      neurocomputational plasticity. But catecholamines are also easily oxidized to
      neurotoxic 0-semiquinones and this may be relevant to the pathology of several
      diseases including schizophrenia. The relationship between dopamine release and
      positive reinforcement is relevant to this hypothesis.

PMID- 9149427
TI  - A novel neuropeptide-endocrine interaction controlling ecdysteroid production in
      ixodid ticks.
AB  - Ixodid (hard) ticks are blood-feeding arthropods that require a blood meal to
      complete each stage of development. However, the hormonal events coordinating
      aspects of feeding and development are only poorly understood. We have delineated
      a new neuropeptide-endocrine interaction in the adult tick, Amblyomma hebraeum,
      that stimulates the synthesis of the moulting hormones, the ecdysteroids. In
      adult female ticks, ecdysteroid synthesis could be demonstrated in integumental
      tissue incubated in vitro with a synganglial (central nervous system) extract,
      but not in its absence. Stimulation by the synganglial extract is both time- and
      dose-dependent, but is completely abolished by trypsin treatment, suggesting that
      the activity is due to a peptide/protein. Integumental tissue ecdysteroidogenesis
      is also stimulated by elevation of the cAMP concentration using forskolin and 3
      isobutyl-l-methyl-xanthine, or by 8-bromo-cAMP. This suggests the involvement of
      at least a cAMP second messenger system in the neuropeptide-ecdysteroidogenesis
      axis, without precluding a role for other second messengers as well. Despite
      involving a quite different steroidogenic tissue, the foregoing system has some
      parallels with the known prothoracicotropic hormone (neuropeptide)-prothoracic
      gland endocrine axis of insects.

PMID- 9149428
TI  - A quantitative comparison of mechanoelectrical transduction in vestibular and
      auditory hair cells of neonatal mice.
AB  - Vestibular hair cells (VHCs) and cochlear outer hair cells (OHCs) of neonatal
      mice were stimulated by a fluid jet directed at their stereociliary bundles.
      Relations between the force exerted by the jet, bundle displacement, and the
      resulting transducer current were studied. The mean maximum transducer
      conductance in VHCs (2.6 nS) was about half that of the OHCs (5.5 nS), with the
      largest recorded values being 4.1 nS and 9.2 nS, respectively. In some OHCs
      activity of a single, 112 pS transducer channel was observed, allowing an
      estimate of the maximum number of channels: up to 36 in VHCs and 82 in OHCs,
      corresponding to about one transducer channel per tip link. The VHC bundles
      required about 330 nm of tip displacement to activate 90% of the maximum
      transducer conductance, compared to 150 nm for the OHC bundles. This corresponded
      to 2 deg of rotation about their pivots for both, due to the greater length of
      the VHC bundles. The VHC bundles' translational stiffness was one-seventh of that
      of the OHCs. Conversion to rotational stiffness almost abolished this difference.
      Rotation of the hair bundle rather than translation determines the gating of the
      transducer channels, independent of bundle height or origin of the cells.

PMID- 9149430
TI  - Profiling peptide adducts of oxidized N-acetyldopamine by electrospray mass
      spectrometry.
AB  - Phenolic and catecholamine polymers are common constituents of many biological
      systems. Cross-linking of polyphenols with other phenols, peptides, proteins and
      carbohydrates results in the synthesis of complex natural products which are not
      easily characterized. Electrospray mass spectrometry (ES-MS) and tandem mass
      spectrometry (ES-MS/MS) were used to identify polymers of oxidized N
      acetyldopamine (NADA) and peptide adducts with oxidized NADA. Following
      incubation with mushroom tyrosinase, NADA adducts of trityrosine were identified.
      It was not possible to locate the site of NADA binding to this tripeptide.
      Compounds formed by incubation of N-acetylhistidine and N-acetyllysine with
      oxidized NADA, previously characterized using classical chemical techniques, were
      confirmed using ES-MS/MS. The peptide angiotensin (DRVYIHPFHL) was used as a
      model substrate to determine whether the site(s) to which oxidized NADA bound
      could be determined. The lot of angiotensin used was contaminated with a peptide
      of mass 14 u greater than angiotensin, and it was found that the H in position 9
      of the contaminant peptide was modified. ES-MS/MS of the angiotensin and the
      contaminant peptide following incubation with oxidized NADA revealed that the C
      terminal aspartic acid was the primary amino acid to which NADA adducts were
      covalently bound, but other residues were also modified. Femto-molar sensitivity
      for analysis of complex mixtures of catecholamine-peptide adducts will facilitate
      structural elucidation of natural products not amenable to characterization using
      other spectroscopic techniques.

PMID- 9149429
TI  - Collision-induced dissociation of polyprotonated oligonucleotides produced by
      electrospray ionization.
AB  - The efficient production of polyprotonated oligonucleotides, studied at n < or =
      19, occurs from water/propan-2-ol solutions over an ammonium acetate
      concentration range between 2.5 and 40 mm and a pH range from 5 to 11. Average
      charge-state levels observed were approximately half of those found in mass
      spectra of polyanionic oligonucleotides, reflecting differences in sites of
      ionization: heterocyclic bases for protonation and phosphodiester backbone for
      deprotonation. Collision-induced dissociation mass spectra show three principal
      reaction paths: (1) release of protonated bases, with abundances dictated largely
      by base proton affinity; (2) phosphodiester chain cleavage at C3'-O3' indicative
      of sequence in the 3'-->5' direction; and (3) chain cleavage concomitant with
      base loss giving furan-type ions indicative of sequence in the 5'-->3' direction,
      analogous to reactions of polyanionic oligonucleotides. Thymine residues undergo
      very little protonation, resulting in characteristic absence of phosphodiester
      cleavage on the 3' side of T sites, producing mass-ladder gaps representing
      dinucleotides.

PMID- 9149432
TI  - Effect of cyclodextrins on the hydrolysis of an oxazolidine prodrug of (1R,2S)-(
      )-ephedrine-cis-2-(4-methoxyphenyl)-3, 4-dimethyl-5-phenyloxazolidine.
AB  - Molecular complexes of an oxazolidine prodrug of (-)-ephedrine, cis-2-(4
      methoxyphenyl)-3,4-dimethyl-5-phenyloxazolidine, with alpha-, beta-, dimethyl
      beta- (DM-beta-) and hydroxypropl-beta- (HP-beta-) cyclodextrins (CDs) were
      examined using ionspray mass spectrometry. The results suggest, under our
      experimental conditions, a 1:1 stoichiometric complex between the prodrug and all
      CDs. Apart from the putative inclusion complexation, the stabilization effect of
      CDs on the prodrug in an aqueous solution was studied. beta-, DM-beta- and HP
      beta-CD exhibited a retardation effect on the rate of hydrolysis of the prodrug.
      Conversely, alpha-CD did not alter the rate of hydrolysis even at excess
      concentrations. Presumably, the larger cavity diameter of beta-CDs may permit a
      greater depth of penetration of the prodrug, resulting in its shielding from
      hydrolysis. The observations in this work indicate that mass spectrometry could
      be a rapid and informative analytical method to aid in the preliminary evaluation
      of the potential utility of CDs in enhancement of drug stability.

PMID- 9149433
TI  - Influence of solvents and detergents on matrix-assisted laser
      desorption/ionization mass spectrometry measurements of proteins and
      oligonucleotides.
AB  - The effect of solvents was found to be critical for sample preparation in matrix
      assisted laser desorption/ionization mass spectrometry (MALDI-MS). For proteins
      and oligonucleotides the use of 2-propanol/water as a solvent for different
      matrices can significantly improve the quality of spectra. This effect is
      demonstrated with proteins ranging in molecular weight from 12 to 150 kDa and
      with a special 19-mer oligonucleotide. A comparison of MALDI-MS using of 2
      propanol as matrix solvent and high-performance capillary electrophoresis
      resulted in identical relative peak intensities for a p(dT)12-18 oligonucleotide
      mixture. Additionally, the effect of detergents for characterization of high
      molecular weight proteins in very dilute solutions was studied with this solvent.
      It was found that Triton X-100, up to a concentration of 1%, was highly
      compatible with MALDI measurements and even could improve the quality of spectra.
      Use of detergents for cell profiling has extended the detectable mass range to
      about m/z 75,000.

PMID- 9149434
TI  - Isolation and characterization of proteins from human lymphocyte nuclei using
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and
      post-source decay analysis.
AB  - The cell nucleus plays an essential role in all aspects of cell function,
      including DNA replication, gene transcription, RNA processing and cell division.
      Within the cell nucleus there are many proteins and peptides that have regulatory
      roles. Although several higher molecular weight protein components (> 30 kDa)
      have been identified and characterized, limited information is available for the
      lower molecular weight components. Nuclei from human peripheral blood lymphocytes
      were isolated and rapidly characterized by employing a strategy using reversed
      phase high-performance liquid chromatography, tryptic digestion, and post-source
      decay analysis of matrix-assisted laser desorption/ionization (MALDI) ions in
      combination with database searches. Database searches utilizing molecular weight,
      proteolytic digest fragments, and peptide sequence results identified known
      proteins. The results illustrate the usefulness of MALDI as a tool in the
      characterization of low abundance proteins in the cell nucleus.

PMID- 9149435
TI  - A highly specific method for the characterization of glycation and glyco
      oxidation products of globins.
AB  - A new method, based on matrix-assisted laser desorption/ionization (MALDI)
      measurements, has been developed for the evaluation of the glycation level of
      globins, a relevant parameter for diabetes control. It shows high levels of
      reproducibility and specificity, allowing the different glycated and glyco
      oxidized products of both alpha- and beta-globins to be distinguished. Such
      specificity is reflected in its possible diagnostic use not only for the control
      of diabetes, but also for the occurrence of 'oxidative stress'. The comparison,
      for the same samples, of the obtained MALDI data with the related HbA1c values,
      determined by a high performance liquid chromatographic method, allowed it to be
      established that HbA1c percentages are not, as usually retained, related to the
      simply glycated beta-globin, but to the whole pool of glycated and glyco-oxidized
      alpha- and beta-globins.

PMID- 9149436
TI  - Mass spectrometry in the study of non-enzymatic glyco-oxidation of proteins.
AB  - Studies that have been performed by MALDI mass spectrometry in the field of non
      enzymatic protein glyco-oxidation are briefly reviewed. The results obtained by
      in vitro and in vivo experiments demonstrate the power of this technique, which
      is able to give information on the number of sugar molecules condensed on
      specific proteins and, consequently, represents a new and specific diagnostic
      tool in diabetes control.

PMID- 9149437
TI  - A short story about the life of Curt Brunnee.

PMID- 9149438
TI  - Exogenous heparin induces fibronectin overexpression parallel to angiogenesis in
      the extracellular matrix of the chick embryo chorioallantoic membrane.
AB  - Heparin (HE) was injected into the allantoic sac of chick embryo eggs on the 5th
      day of incubation. After 48 h, a morphometric analysis of angiogenic response and
      an immunohistochemical investigation of fibronectin (FN) and type IV collagen
      immunoreactivity in developing vasculature were performed in order to verify
      whether HE-related choriollantoic membrane (CAM) angiogenic activity was
      associated with overexpression of FN and/or type IV collagen changes in CAM
      extracellular matrix. Data to be presented show a close relationship between HE
      treatment, angiogenic processes, and overexpression of FN, but not of type IV
      collagen in CAM extracellular matrix. They agree with other studies proving a
      facilitating role of FN in angiogenic processes.

PMID- 9149439
TI  - Collagen type VI is a component of the extracellular matrix microfibril network
      of the prostatic stroma.
AB  - Stroma-epithelium relationships are of great relevance in prostatic morphogenesis
      and physiology. However, little knowledge exists about either stromal cells or
      extracellular matrix composition and arrangement in this system. Ultrastructural
      analysis revealed the existence of a microfibrillar system which occupies large
      areas of the rat prostatic stroma. In this work, we have applied
      immunocytochemistry and an ATP treatment for the ultrastructural identification
      of collagen type VI microfibrils, aiming at examining its participation in the
      prostatic microfibrillar network. Immunocytochemistry was also extended to a
      human case of prostatic nodular hyperplasia. Both methods succeeded in
      identifying collagen type VI in the rat ventral prostate. Collagen type VI is
      evenly distributed throughout the stroma but mainly associated with the basal
      lamina, collagen fibrils, and around the stromal cells. The use of ATP treatment
      allowed for the discrimination between collagen type VI and elastin-associated
      microfibrils, and demonstrated that these two classes of microfibrils establish
      an extended, mixed, and open network. The same aspects of association with the
      basal lamina, with stromal cells (particularly with smooth muscle cells), and
      with fibrillar components of the stroma were observed in the human tissue. We
      suggest that the collagen type VI and elastin-associated microfibril system may
      be involved in the control of some aspects of cellular behavior and may also play
      a structural role, maintaining the organ integrity after the deformations
      occurring under smooth muscle contraction.

PMID- 9149440
TI  - The polycystic ovarian (PCO) condition: apoptosis and epithelialization of the
      ovarian antral follicles are aspects of cystogenesis in the
      dehydroepiandrosterone (DHEA)-treated rat model.
AB  - This investigation was designed to study apoptosis and epithelialization during
      cystogenesis of the dehydroepiandrosterone rat model. Using in situ DNA 3'- end
      labeling with non-radioactive digoxigenindidesoxy-UTP (dig-ddUTP), apoptosis is
      initially seen in cumulus granulosa cells and other granulosa cells facing the
      antrum. During cystogenesis, apoptosis systematically progresses from the cumulus
      towards the mural granulosa layer. In contrast, granulosa cells of atretic
      follicles undergo apoptosis in a random manner. The outer layer of mural
      granulosa cells during cystogenesis escapes apoptosis. Granulosa cells contain
      vimentin. However, the outer mural granulosa cell layer that lines the cyst
      acquires keratin. In addition to being associated with each other via gap
      junctions, the outer layer of granulosa cells acquire tight junctions. With the
      characterization of the transformation of the outer mural granulosa cells into a
      characteristic epithelium and the orderly progression of apoptosis, we further
      the understanding of the multifaceted process of cystogenesis of the ovarian
      antral follicle.

PMID- 9149441
TI  - Ultrastructure of cholesterol gallstones as observed by electron microscopy after
      freeze-fracturing.
AB  - The ultrastructure of cholesterol gallstones (mixed type) was studied in detail
      for the first time under the transmission electron microscope after freeze
      fracturing. Gallstones consisted essentially of cholesterol crystals, some
      impurities, and fluid. In accord with the theoretical 3.4 nm bilayered structure
      of cholesterol crystals, 3-4 nm periodicity of crystal layering was observed.
      However, gallstone cholesterol crystals were not perfect and often showed
      structural defects. Between crystals, complete edge-to-surface, edge-to-edge and
      surface-to-surface adhesions, and overall block-like aggregations were found.
      These may represent the structural basis for the stability of cholesterol crystal
      aggregation. The easy breakdown of cholesterol gallstones by extracorporeal shock
      wave lithotripsy is discussed in relation to their ultrastructure.

PMID- 9149442
TI  - Immunohistochemical localization of serotonin, galanin, cholecystokinin, and
      methionine-enkephalin in adrenal medullary cells of the chicken.
AB  - The identification of adrenaline- (A) and noradrenaline- (NA) containing cells in
      the adrenal medulla of the chicken and colocalization of serotonin and
      neuropeptides with A or NA in medullary cells were investigated with the use of
      immunohistochemical methods. Antisera against tyrosine hydroxylase and
      phenylethanolamine-N-methyltransferase were used as markers for catecholamine-
      and A-synthesizing cells, respectively. About 70% of catecholamine-synthesizing
      cells also exhibited immunoreactivity for phenylethanolamine-N-methyltransferase
      antiserum. Therefore, these cells are A-containing ones and the rest of cells
      seem to be NA-containing cells. Immunoreactivity with serotonin antiserum was
      observed in almost all medullary cells. Galanin-immunoreactivity was also found
      throughout the adrenal medulla, but was stronger in A-containing cells than in NA
      containing ones. Cholecystokinin-immunoreactivity was restricted to A-containing
      cells. Methionine-enkephalin-immunoreactivity was seen in both A- and NA
      containing cells, but in about half of medullary cells. From these results, it is
      suggested that serotonin, galanin, cholecystokinin, and methionine-enkephalin may
      be co-released with A and/or NA from adrenal medullary cells of the chicken.

PMID- 9149443
TI  - Conditions for the culture of bovine embryonic myogenic cells.
AB  - The objective of this experiment was to determine the growth characteristics of
      bovine embryonic muscle cells and to optimize the growth conditions for these
      cells using commercially-prepared media and sera. In the first study, the growth
      of muscle cells isolated from the hindlimb was determined by measuring DNA
      content. The DNA concentration was lowest (P < 0.001) at 24 h post-plating and
      increased to a maximum at approximately 60 h. The slopes of creatine kinase
      activity and fusion index curves were similar to the DNA; however, the creatine
      kinase activity achieved a maximum at 140 h post-plating, while the fusion index
      reached maximum at 120 h. In the second study, cells were cultured on different
      substrata, either plastic, gelatin, or collagen. There were no differences (P >
      0.05) in the cell growth rates for any of the three substrata. In the third
      study, cells were grown in 10% fetal bovine serum (FBS) and either a balanced
      salt solution (BSS; 30 mM Hepes, 10 mM glucose, 120 mM NaCl, 2.5 mM Na2HPO4, and
      3 mM KCl), McCoy's 5A, Dulbecco's Minimal Essential Medium/Ham's F12 (DMEM/F12),
      or 70% DMEM/20% M-199. Cell numbers adhering to the plate at 26 h post-plating
      were different (P > 0.001) between each medium (DMEM/M-199 > McCoy's 5A >
      DMEM/F12 > BSS). Cell proliferation rates for each treatment medium were greatest
      for DMEM/M-199, followed by McCoy's 5A, DMEM/F12, and BSS. Cell differentiation
      was highest (P < 0.05) in the DMEM/F12, followed by McCoy's 5A, DMEM/M-199, and
      BSS. In the final study, the cells were treated with different sources of serum
      added at 10% to DMEM/M-199. The sera consisted of FBS, newborn calf serum (NCS),
      horse serum (HS) and iron-supplemented calf serum (Fe(2+)-CS). The cells were
      added to each well at 10(4) cells. At 24 h post-plating, the serum-free, NCS, and
      FBS-treated cell numbers were greater (P < 0.05) than the cells treated with HS
      or Fe(2+)-CS, which may reflect the efficient adherence to the surface or faster
      adaptation to the serum by the cells. The proliferation rate was greatest (P <
      0.001) for the cells treated with Fe(2+)-CS, followed by FBS = NCS, HS, and no
      serum. Therefore, the muscle cells obtained from bovine embryos grow and
      differentiate similar to muscle cells from other species. The optimal growth
      medium for growing these cells in vitro is DMEM/M-199 plus 10% Fe(2+)-CS, while
      the optimal differentiation medium is McCoy's 5A.

PMID- 9149444
TI  - Impala, Aepyceros melampus, platelets: count, morphology, and morphometric
      observations.
AB  - There is little published information regarding the platelets of impala
      (Aepyceros melampus). In this study we determined the platelet counts of 12
      healthy adult male impalas and describe the morphology of the platelets. The
      platelet counts of the animals are high. Although the platelets appear to be
      extremely small, they have the characteristic ultrastructure of the platelets of
      the family Bovidae. They have few but prominent alpha-granules. Other cytoplasmic
      inclusions are the dense bodies, microtubules, mitochondria, and glycogen. There
      is no surface-connecting canalicular system present.

PMID- 9149445
TI  - Determination of the unit size of the corneal endothelial cell mosaic from
      Fourier component image analysis.
AB  - Scanning electron micrographs were taken of the central region of the corneal
      endothelium of cows (Holstein). The cells were outlined and an image overlay
      generated of approximately 100 cells. Via a Windows-based scanning system, the
      overlay was subjected to a two-dimensional Fourier transform on a Unix-based
      system. A custom algorithm was developed (IRIS) to sequentially analyse the
      Fourier transform pattern. The transform and resultant harmonics spectrum were
      compared to those obtained from artificial cell mosaics generated from uniform
      sized symmetrical hexagons. The position, width, and height of the 1st harmonic
      component of the frequency distribution appears to be derived from average cell
      cell border distances across the image. The radial position of the 1st harmonic
      is inversely related to the unit cell size in the mosaic, i.e. the dominant cell
      size. The application of such techniques to cell mosaic analyses is discussed.

PMID- 9149446
TI  - Three division-competent, structurally-distinct cell populations contribute to
      murine mammary epithelial renewal.
AB  - Markers for the division-competent cells in mammary gland epithelium are
      important to the understanding of normal and neoplastic mammary epithelial growth
      and architectural maintenance, but have been difficult to reveal. Using the
      presence of condensed chromosomes as an indicator of division competence, we have
      described morphological markers in the nucleus and cytoplasm that reliably
      characterize two sets of structurally-distinct, division-competent cells in
      murine (i.e. mouse and rat) mammary epithelium. The markers, based, in part, on
      cell size, nuclear and cytoplasmic staining characteristics, and distinctive
      morphological features of the nucleus and cytoplasm allow classification of the
      division-competent cells into two categories: 'large light cells' and 'small
      light cells'. Based on the degree of cytoplasmic organelle differentiation, the
      small light cells are the least differentiated cells in the epithelium, and the
      large light cells appear, structurally and functionally, to be in the early
      stages of secretory differentiation. We demonstrate, using statistical analysis
      of cell counts (per unit area of epithelium) from four stages of mammary
      epithelial growth, that there are, in fact, three division-competent cell
      populations in the rat mammary epithelium, and that the large light cell is a
      direct precursor to terminally differentiated cells, both secretory and
      myoepithelial. Using our results we synthesize a morphological model of cell
      mitosis and the progression of epithelial differentiation in murine mammary gland
      from a stem cell through two progenitors.

PMID- 9149448
TI  - Underprediction of pain in children undergoing ear piercing.
AB  - Ear piercing is a brief, standard, painful stimulus which is submitted to
      voluntarily, offering a unique opportunity for research on children's
      anticipation of pain in a naturalistic context. Self-ratings on visual analogue
      scales of fear, predicted pain, and experienced pain were collected, as each ear
      was pierced in turn, from 32 girls aged 5-11 yr. Of these, 69% underpredicted
      their pain on the first ear. These underpredictors of pain on the first ear
      expected and reported significantly greater pain when the second ear was pierced
      than did overpredictors or children who accurately predicted the pain for the
      first ear. Fear scores taken before the first ear was pierced did not
      significantly predict pain for the second ear. Younger children made less
      accurate predictions and were more likely to use the extremes of the scale. The
      results, which are consistent with those of previous studies of prediction of
      pain and anxiety, have implications for preparation of children for brief
      procedural pain: they support recommendations to encourage children to expect
      realistic rather than minimal amounts of pain.

PMID- 9149447
TI  - Body image disturbances and their change with videofeedback in anorexia nervosa.
AB  - Disturbance in the way the body is experienced is a diagnostic criterion for
      anorexia nervosa, and impedes recovery. A method relatively free of external
      prompts, to reduce the potential for experimentally induced biases, evaluated
      body image distortions (BID) in 18 patients with anorexia nervosa soon after
      admission to an inpatient unit, and 18 normal controls, before and after a
      videofeedback session. The BID were assessed in the affective and self/social
      domains by visual analogue scales in which the instructional set oriented
      subjects to (a) the sensation of fatness (Affective Response, AR), and (b) size
      compared with other young women (Comparative Size Response, CSR). The AR and CSR
      were significantly greater than normal in anorexia but decreased significantly
      with videofeedback, while values for controls were stable. The AR and CSR were
      only partially independent, indicating overlap of the domains. In anorexia only,
      the responses were related to two DSM-IV diagnostic criteria for anorexia, fear
      of gaining weight and health-weight concerns, as well as to drive for thinness
      and body dissatisfaction. Fear of gaining weight occupied a central position in
      determining the magnitudes of BID and the other measures, including anxiety and
      depression.

PMID- 9149449
TI  - Looming vulnerability to spreading contamination in subclinical OCD.
AB  - The present study examined the hypothesis, stimulated by the looming
      vulnerability model of anxiety (Riskind, in press, Behaviour Research and
      Therapy), that subclinical OCD is associated with a subjective sense of looming
      vulnerability. One-hundred and four undergraduates rated vignettes of common,
      everyday situations involving exposure to possible dirt, germs, or contamination.
      Participants in a subclinical obsessional group had a far higher sense of looming
      vulnerability to spreading contamination than did those in a control group.
      Results verified that the subjective sense of looming vulnerability still had
      separate, distinct and significant contributions to fear-of-contamination
      symptoms, with the effects of cognitive appraisals of other aspects of threat
      (such as probability of harm, or lack of control) removed. In contrast, these
      other cognitive appraisals had no significant associations with symptoms that
      proved to be independent of the subjective sense of looming vulnerability. A path
      analysis further explored the dependency of these other cognitive appraisals on
      looming vulnerability. This analysis found that part of the effects of the
      subjective sense of looming vulnerability on fears may be indirect and mediated
      via correlated effects of other cognitive appraisals.

PMID- 9149450
TI  - Covariation bias for phylogenetic versus ontogenetic fear-relevant stimuli.
AB  - In the present study, two groups of 21 subjects with either high or low fear of
      both snakes (or spiders) and damaged electrical outlets/appliances participated
      in a two phase experiment. After reading a description of an illusory correlation
      experiment, subjects were asked to imagine themselves participating in it. They
      rated their expectations for the number of occasions on which slides of snakes,
      electrical outlets, and flowers would be followed by either a shock, tone, or
      nothing. As predicted, both high and low-fear subjects reported an expectancy
      bias for both phylogenetic and ontogenetic fear-relevant stimuli and shock. In
      the second phase subjects were actually exposed to the random slide/outcome
      presentation. Only high-fear subjects demonstrated a covariation bias which was
      specific to phylogenetic fear-relevant slides and shock, indicating all other
      biases were effectively attenuated.

PMID- 9149451
TI  - Excessive responsibility in obsessional concerns: a fine-grained experimental
      analysis.
AB  - Excessive responsibility has been suggested as a central cognitive variable
      associated with Obsessive-Compulsive Disorder (OCD) (Rachman, 1993, Behaviour
      Research and Therapy, 31, 149-154; Salkovskis, 1985, Behaviour Research and
      Therapy, 23, 571-583; Salkovskis, 1989, Behaviour Research and Therapy, 27, 677
      682; Salkovskis, 1995, Current controversies in the anxiety disorders). Several
      studies using questionnaires (e.g. Rheaume, Freeston, Dugas, Letarte & Ladouceur,
      1995, Behaviour Research and Therapy, 33, 785-794) and experimental manipulations
      (Ladouceur et al., 1995, Behaviour Research and Therapy, 33, 937-946; Lopatka &
      Rachman, 1995, Behaviour Research and Therapy, 33, 673-684) have shown evidence
      for such a link between responsibility and obsessive-compulsive symptoms.
      Responsibility has been defined as the belief of possessing a pivotal power to
      provoke or preventing crucial negative consequences (Salkovskis et al., 1992
      cited in Salkovskis, 1995, Current controversies in the anxiety disorders). This
      definition emphasizes two related cognitive distortions: personal influence and
      potential negative consequences. The respective roles of each component and their
      potential interaction need to be clarified. The present study tests the effects
      of an experimental manipulation of both influence and negative consequences on
      perceived responsibility and checking behavior during a classification task.
      Seventy-seven subjects were divided into four experimental conditions: the
      Combined condition, the Influence condition, the Negative Consequences condition
      and the Control condition. After the experimental manipulation, subjects from
      each condition had to classify capsules in semi-transparent bottles. Results
      showed that personal influence is the best predictor of perceived responsibility.
      Although increased potential negative consequences were sufficient to trigger
      hesitations, combined influence and negative consequences were necessary to
      produce modifications. These results are consistent with the results obtained by
      the questionnaires (e.g. Rheaume, Ladouceur, Freeston & Letarte, 1995a, Behaviour
      Research and Therapy, 33, 159-169) and previous manipulations (e.g. Ladouceur et
      al., 1995).

PMID- 9149452
TI  - Scholastic impairments among traumatized adolescents.
AB  - This investigation sought to determine if exposure to exceptional stress is
      associated with academic deficits or whether academic deficits are specifically
      associated with post-traumatic stress disorder (PTSD). In order to address these
      questions, the Metropolitan Achievement Test (MAT) as well as a measure of
      intelligence were administered to three groups of Lebanese adolescents. The first
      group met diagnostic criteria for PTSD. The second group had been exposed to
      qualitatively and quantitatively similar stressors but did not meet diagnostic
      criteria for PTSD. The third group consisted of nontraumatized controls. Data
      analysis using IQ as a covariate determined that the MAT scores of the PTSD
      subjects were significantly lower than the scores of the stress exposed PTSD
      negatives and controls. No significant differences were observed when the MAT
      scores of the stress exposed PTSD negatives and controls were compared.

PMID- 9149453
TI  - Expectancy variables predicting tolerance and avoidance of pain in chronic pain
      patients.
AB  - Previous research on anxiety and some recent reports on chronic pain suggest that
      the response to aversive stimuli may be influenced by expectations rather than
      actual experience. This study examined the contributions of four expectancy
      related variables to the tolerance and avoidance of pain: pain expectancy,
      response expectancy, self-efficacy expectancy, and danger expectancy. Chronic
      pain sufferers volunteered to undergo cold pressor pain on two trials (the first
      for practice, and the second to determine tolerance) and then faced the prospect
      of a third trial (to determine avoidance). It was found that expected tolerance
      (or response expectancy) significantly predicted actual tolerance, whereas
      expected danger significantly predicted avoidance. These findings are in partial
      agreement with previous research. Among the clinical implications are that
      chronic pain sufferers generally associate pain with damage and they predict
      their pain tolerance well; they do not necessarily escape from a compulsory
      activity that produces pain, but given the chance they would rather avoid it in
      the first place.

PMID- 9149454
TI  - Primary obsessional slowness: long-term findings.
AB  - Cases of slowness among patients who spent large amounts of time to perform daily
      activities were first reported in 1974, and described as primary obsessional
      slowness (POS). It was observed that it was neither obsessive thoughts nor
      compulsions that directly hindered their daily activities. However, in more than
      20 years following the original report, the diagnostic independence of POS
      remains controversial, some insisting that obsessional slowness can be explained
      as secondary. The authors experienced four cases in Japan which share the same
      characteristics as the original cases. Long-term observation and treatment has
      led us to support the diagnostic independence of POS. Slowness remained after
      other accompanying symptoms of obsessive-compulsive disorder had been
      successfully treated, showing that the slowness of our patients was not
      secondary.

PMID- 9149455
TI  - Information processing in anxiety and depression.
AB  - Performance on explicit and implicit memory tasks was compared among non-clinical
      participants (N = 47) who reported low anxiety and low depression, high anxiety
      and low depression, or high anxiety and high depression. No differences were
      found among the groups in explicit memory. Differences in our measure of implicit
      memory were attributable to higher anxiety, regardless of depression. Increased
      implicit memory was specific to personally relevant information. The study
      highlights the need for further exploration of information processing in mixed
      anxiety and depression.

PMID- 9149456
TI  - The Blood-Injection Symptom Scale (BISS): assessing a structure of phobic
      symptoms elicited by blood and injections.
AB  - Assessments for blood-injury-injection phobia measure feared stimuli and overt
      behaviours, but they have not systematically addressed the symptoms of fear and
      faintness. The Blood-Injection Symptom Scale (BISS) was developed to overcome
      this omission. An exploratory factor analysis grouped symptoms triggered by blood
      and injections into three internally consistent factors (faintness, anxiety and
      tension). A confirmatory factor analysis replicated the factor structure in a new
      sample. To test the construct validity of the BISS, an attempt was made to
      reproduce Ost's (1992, Journal of Abnormal Psychology, 101, 68-74) finding that
      fear was stronger among people with concerns about injections, while faintness
      was stronger among people with concerns about blood. A community sample of 80
      individuals with concerns (i.e. fear or fainting) about blood or injections
      completed the BISS. Controlling faintness, individuals with concerns about
      injections reported more fear than people with concerns about blood. In contrast,
      controlling for fear, the latter reported more symptoms of faintness. These data
      suggest that the BISS generates stable and internally consistent subscales useful
      in the measurement of symptoms elicited by blood and injections.

PMID- 9149457
TI  - Measurement of antecedents to drug and alcohol use: psychometric properties of
      the Inventory of Drug-Taking Situations (IDTS).
AB  - The development, factor structure, and validity of the Inventory of Drug-Taking
      Situations (IDTS) is described. This 50-item self-report questionnaire, which is
      an extension of the Inventory of Drinking Situations (Annis, 1982. Inventory of
      drinking situations; Annis, Graham & Davis, 1987, Inventory of drinking
      situations (IDS): User's guide), is designed to assess the situational
      antecedents to use of a wide range of drugs of abuse. The IDTS consists of 8
      subscales that measure a client's substance use in the 8 situations identified in
      the work of Marlatt (1978, Alcoholism: New directions in behavioral research and
      treatment): Unpleasant Emotions, Physical Discomfort, Pleasant Emotions, Testing
      Personal Control, Urges and Temptations to Use, Conflict with Others, Social
      Pressure to Use, and Pleasant Times with Others. Reliability, factor structure
      and validity of the IDTS were assessed on 699 clients admitted to the Addiction
      Research Foundation's treatment facility in Toronto. The IDTS was shown to have
      reliable subscales. The IDTS total score correlated with self-ratings of the
      severity of the clients' substance use problem, and with retrospective reports of
      frequency of use (drugs) and quantity of use (alcohol), years of usage, and
      severity of dependence. Confirmatory factor analysis was used to test the fit of
      the data to Marlatt's model of substance use situations, as well as to several
      alternative models. The goodness-of-fit indicators suggested that the best fit
      for the data was an 8-factor model corresponding to the 8 subscales based on the
      Marlatt categories. Evidence was presented that the 8 subscales can be further
      grouped into 3 second-order factors: (1) negative situations, (2) positive
      situations, and (3) temptation situations. The negative situation subscales of
      Unpleasant Emotions, Conflict with Others and Physical Discomfort were found to
      be correlated with the SCL-90R Depression scale. Interpersonal Sensitivity scale
      and Somatization scale respectively. The positive social situation subscales of
      Pleasant Times with Others and Social Pressure to Use were found to be negatively
      correlated with percentage of time using alone, and positively correlated with
      pressure from friends and family to use. On the States of Change Readiness and
      Treatment Eagerness Scales (SOCRATES), clients at the precontemplation stage of
      change had relatively flat, undifferentiated IDTS profiles (i.e. little scatter
      of subscale scores), whereas clients in the determination stage had the most
      differentiation in their IDTS subscale scores. Excellent comparability was found
      for alcohol clients between the IDS and the IDTS. Evidence was also presented for
      adequate comparability between the computer and paper and pencil administrative
      formats of the IDTS.

PMID- 9149458
TI  - New perspectives in clinical practice. Introduction.

PMID- 9149459
TI  - The evolution of adjustment issues in HIV/AIDS.
AB  - The issues of emotional adjustment to AIDS have been inextricably linked to
      medical advances in fundamental knowledge about the human immunodeficiency virus
      and its potential therapies. In 1987 patients were struggling with the advantages
      and disadvantages "to do or not to do AZT (zidovudine)," whereas the choices
      imposed by combination therapies and the protease inhibitors in 1997 are
      fundamentally different and are occurring in an evolving context created by a
      number of striking medical advances, expanding populations, the availability of
      environmental support, and changing public sentiments. As the psychiatric
      treatment of HIV-positive individuals shifts increasingly from "AIDS specialists"
      to the wider therapeutic community, it is important that the therapist who has
      had relatively little experience with this population not assume that
      contemporary issues and concerns of the seropositive patient, or the patient with
      AIDS, are essentially those discussed widely in the earlier years of the
      epidemic. Patients living with this virus for a number of years have traveled a
      long and arduous journey and will experience more empathy from a therapist who
      has some knowledge of that path. Awareness of the evolution of emotional
      adjustment, counseling, and ethical issues of AIDS should amplify the general
      fund of knowledge required for good clinical management of the person living with
      AIDS.

PMID- 9149460
TI  - Contemporary treatment of schizophrenia.
AB  - Over the past decade the treatment of schizophrenia has changed in each of its
      biopsychosocial domains. Advances in neuroscience, particularly in the knowledge
      of the receptor site, led to increased effectiveness of antipsychotic medication.
      Development of more sophisticated psychoeducational and rehabilitative techniques
      enhanced the chances for fuller recovery. Evolution from therapeutic community to
      continuum of care replaced the traditional inpatient setting with a range of more
      ambulatory-based alternatives. Comprehensive treatment matches these changes with
      the phase of illness and is reinforced with a flexible and supportive
      psychotherapy that emphasizes medication compliance and educational and problem
      solving tasks.

PMID- 9149462
TI  - Depression in the context of late-life transitions.
AB  - Late-life transitions shape feelings, yet these transitions are often overlooked
      when considering the mental state of older persons. The author discusses late
      life transitions and how change in late life can present a challenge for growth.
      An understanding of these developments is necessary for mental health
      professionals trying to assess and treat depression in the elderly. Accurate
      assessment of depressive symptoms in late life requires a multifaceted, age
      adjusted understanding of the unique characteristics of life's later years. Such
      an understanding can be fostered by learning to appreciate the patina that
      develops from decades of living. Properly focused treatment can promote further
      maturation in response to the vagaries of life. Change can be fostered by an
      openness to the possibility of late-life development.

PMID- 9149461
TI  - A psychoeducational program for patients with trauma-related disorders.
AB  - The authors describe the development and implementation of a psychoeducational
      program for patients with a wide range of trauma-related symptoms and disorders.
      The psychoeducational intervention is designed to facilitate coping, promote self
      understanding, and enhance reflectiveness. Using attachment theory as the
      overarching conceptual framework, the authors educate patients about the nature
      of trauma, the effects of trauma on development, trauma-related psychiatric
      disorders, and a range of treatment approaches to trauma. They describe groups
      for adult inpatients and adults in partial hospital treatment, and for
      adolescents in either inpatient, residential, or outpatient treatment.

PMID- 9149463
TI  - Fear and anxiety in children and adolescents.
AB  - The author reviews fears and anxiety in children and adolescents. In particular,
      the nature and prevalence of fears and anxiety disorders, including panic
      disorder, are described. This is followed by a description of comorbidity and
      gender differences, and the stability or chronicity of these disorders. Factors
      believed to contribute to the development of childhood fear and anxiety are
      outlined, and finally the treatments for these disorders are reviewed.

PMID- 9149464
TI  - Anxiety disorders in primary care: a life-span perspective.
AB  - From a family-oriented life-span perspective, the authors highlight issues
      involved in recognition, assessment, and treatment of anxiety disorders. After
      reviewing prevalence rates for these disorders in child, adult, and geriatric
      groups, they discuss cross-generational transmission of illness and identify
      cross-cutting themes, such as comorbidity of anxiety and depression, relationship
      between anxiety disorders and quality of life, and links among disability,
      adversity, and anxiety. They also discuss issues specific to childbearing,
      motherhood, and bereavement, and conclude with a brief summary of treatment
      approaches.

PMID- 9149465
TI  - Panic disorder and addiction: the clinical issues of comorbidity.
AB  - Panic disorder and addiction are occasionally comorbid--4.5% of addicted patients
      have panic disorder, and 16% of panic disorder patients are comorbid for
      addiction to alcohol and other drugs. Despite these relatively low rates of
      comorbidity, the treatment of these two disorders is commonly confounded by
      issues of comorbidity, as many physicians avoid using benzodiazepines to treat
      panic disorder out of inappropriate fear of addiction, and not a few physicians
      treat panic disorder thinking that they will thereby end comorbid addiction.
      Sound clinical practice calls for clear identification of both panic disorder and
      addiction and fully effective treatments of the diseases from which the patients
      suffer.

PMID- 9149466
TI  - Panic disorder across the life span: a differential diagnostic approach to
      treatment resistance.
AB  - There has been significant progress over the past 30 years in our understanding
      of the treatment of panic disorder. There are now several different classes of
      pharmacological treatments, as well as cognitive-behavioral treatments that have
      been shown to have efficacy in treating panic disorder. Despite the increase in
      the knowledge base, many patients are only partially responsive or unresponsive
      to initial treatment efforts. A differential diagnostic approach to reviewing
      possible causes for treatment failure is presented. These causes include
      coexisting psychiatric disorders, unrecognized medical factors, environmental
      stressors, and others. Additionally, a review of factors specifically related to
      elderly and to very young treatment-resistant panic disorder patients is
      presented, along with some suggestions for evaluation and treatment. Based on the
      limited literature and clinical experience, practical clinical suggestions for
      approaching identified factors are presented.

PMID- 9149467
TI  - Discussion and overview: what can we learn if we view panic disorder across the
      life span and across different presentations and contexts?
AB  - The author reviews new understanding of the etiology of panic disorder,
      particularly as it involves factors across the life span and across multiple
      presentations. In light of this perspective, he discusses treatment implications.
      He also emphasizes the necessity of increased efforts at case finding, and
      concludes by suggesting directions for future clinical and research strategies.

PMID- 9149468
TI  - Addressing work disability through vocational rehabilitation services.

PMID- 9149469
TI  - Sarcoid arthropathy.

PMID- 9149470
TI  - Rheumatologic manifestations of tuberculosis.

PMID- 9149472
TI  - Digoxin's effect on mortality and hospitalization in heart failure: implications
      of the DIG study. Digitalis Investigation Group.

PMID- 9149471
TI  - A proper role for organized medicine in a new era.

PMID- 9149473
TI  - Troglitazone: a new antihyperglycemic agent.
AB  - Troglitazone is the first of a new family of antihyperglycemic drugs. We review
      its use in clinical practice.

PMID- 9149474
TI  - The protein-sparing modified fast for obesity-related medical problems.

PMID- 9149475
TI  - A 34-year-old woman with odynophagia and weight loss.

PMID- 9149476
TI  - Approach to adult patients with recurrent infections.
AB  - Recurrent infections often reflect underlying abnormalities, either anatomic or
      immunologic. In this paper we review how to recognize the underlying disorders in
      a variety of recurrent infections.

PMID- 9149477
TI  - Chronic hepatitis C: a clinical overview.
AB  - Recent advances in analyzing hepatitis C virus (HCV) have improved understanding
      of how it causes chronic liver disease, although the exact rate of disease
      progression and factors influencing its natural history are not entirely known.
      Tests for HCV fall into two categories: serologic and virologic. Interferon has
      shown limited efficacy in treating chronic HCV infection, and various strategies
      are being tried to improve its efficacy. HCV-related cirrhosis and liver failure
      have become one of the most common indications for liver transplantation in the
      United States.

PMID- 9149478
TI  - A live-virus "suicide" vaccine for human immunodeficiency virus.
AB  - A vaccine that uses a live, attenuated human immunodeficiency virus (HIV) may
      offer the best hope of a vaccine against acquired immunodeficiency syndrome
      (AIDS). A recent improvement should increase the safety of the live-virus
      approach: a "suicide gene" inserted into the viral RNA, which causes infected
      cells to die when treated with ganciclovir. We envision using this strategy not
      only to prevent AIDS, but also to treat it.

PMID- 9149479
TI  - Ethical issues in clinical trials in oncology.

PMID- 9149480
TI  - Coronary stent placement as a bridge to coronary artery bypass surgery in an
      unstable, anemic Jehovah's Witness patient: a case report and review of bloodless
      surgery techniques.
AB  - Bloodless cardiac surgery would be optimal for all patients undergoing major or
      complex heart surgery; however, for Jehovah's Witnesses it involves a religious
      law and is fundamentally mandated. In this context, we review a case of unstable
      angina with associated anemia requiring catheterization and definitive
      intervention in a Jehovah's Witness patient. Coronary stenting to stabilize the
      acute coronary syndrome is described with definitive total revascularization
      performed by coronary artery bypass graft surgery after utilizing erythropoietin
      and aggressive blood conservation techniques.

PMID- 9149481
TI  - The outcome of triplet pregnancies at Hartford Hospital--1989-1996.
AB  - The advent of artificial induction of ovulation has increased the incidence of
      triplet pregnancies. Although the outcome of triplet pregnancies has improved
      through advanced technology, several studies have suggested that triplets
      conceived by artificial induction of ovulation have worse prenatal and perinatal
      outcomes than those conceived naturally. Our study examined the outcome of 14
      sets of triplets conceived at Hartford Hospital between 1989 and 1996. Five of 14
      sets of triplets were conceived by artificial methods and nine of 14 were
      conceived naturally. The mean gestational age was 31.8 weeks for artificially
      conceived infants vs 29.7 weeks for naturally conceived infants. Average weight
      at birth was 1.625 kg in the artificially conceived study group and 1.377 kg in
      the naturally conceived group. Time spent in the neonatal intensive care unit was
      4.67 weeks for the artificially conceived study group and 3.57 weeks for the
      naturally conceived group. It is concluded that there was no difference in
      outcome in the triplets conceived by artificial induction of ovulation vs natural
      conception. Maternal age and sex of triplets were important factors determining
      perinatal outcomes of triplets.

PMID- 9149482
TI  - Pica: are you hungry for the facts?
AB  - Pica, the persistent and compulsive ingestion of particular food items or
      nonnutritive substances, has been associated with iron deficiency, zinc
      deficiency, geophagia, mental deficiency, developmental delay, and a family
      history of pica. Nutritional, sensory physiologic, psychosocial, and cultural
      theories have been advanced to explain this phenomenon, but the etiology of pica
      is poorly understood. Pica, secondary to iron deficiency, is relatively common
      and remits after iron therapy. Complications of pica include abdominal problems
      (sometimes necessitating surgery), lead poisoning, hypokalemia, hyperkalemia,
      mercury poisoning, phosphorus intoxication, and dental injury. Pica is an
      underdiagnosed problem that can be caused by a variety of disorders and can lead
      to serious complications.

PMID- 9149483
TI  - Trends in cancer incidence in Connecticut.
AB  - The population-based Connecticut Tumor Registry was used to examine recent trends
      (1980-84 to 1990-94) in average annual age-standardized incidence rates (ASRs)
      for invasive cancers. Noteworthy were the increase for lung cancer in women (but
      a decline in men), the sharp increase for prostate cancer (but little change in
      female breast cancer), increases for melanoma of skin (both sexes) and non
      Hodgkin's lymphoma (especially in males), and declines for colon and rectum (both
      sexes). Reducing cancer incidence rates will require expanded primary prevention
      efforts, involving mainly behavioral or life-style changes, with an important
      role for primary-care physicians.

PMID- 9149484
TI  - Ceftazidime to cefepime formulary switch: pharmacodynamic and pharmacoeconomic
      rationale.

PMID- 9149485
TI  - Marijuana: current federal law remains in effect.

PMID- 9149486
TI  - Managed care shortchanges children's mental health.

PMID- 9149487
TI  - Are doctors losing their sense of compassion?

PMID- 9149488
TI  - Mismanaged care.

PMID- 9149489
TI  - Reliability, responsibility, and trust.

PMID- 9149490
TI  - Telemedicine today.

PMID- 9149491
TI  - The birth of the RCMI Clinical Research Center is a joint venture of the
      University of Hawaii and Kapiolani Health.
AB  - Hawaii established a Clinical Research Center with collaboration from the
      University of Hawaii Pacific Biomedical Research Center, the John A. Burns School
      of Medicine and Kapiolani Health via a five year award from the Research Centers
      in Minority Institutions of the National Institutes of Health. Support offered
      includes consultative services for protocol design; epidemiological and
      biostatistical analysis; design of study forms; and data and specimen collection
      and analysis.

PMID- 9149492
TI  - The role of the physician in the organ donation process.

PMID- 9149493
TI  - Mercy Health Services: an Iowa physician network.

PMID- 9149494
TI  - The 11th commandment: thou shalt create a compliance program.

PMID- 9149496
TI  - KMA endorses Patient Protection concepts.

PMID- 9149497
TI  - Violence in medical facilities: a review of 40 incidents.
AB  - Workplace violence has become an increasing problem in the United States. This
      paper reviews 40 such incidents of non-patient violence occurring in medical
      facilities. Areas of study include categories of violence, weapons used, number
      of persons killed or wounded, precipitant for the violent act, and the presence
      of psychopathology. Additional variables such as suicide, drug and alcohol use,
      stalking, and hostage-taking are also examined. The results indicate that
      workplace violence in medical settings differs considerably from incidents in
      other work environments, particularly with respect to motivation, psychiatric
      diagnoses, weapons used, and stalking. Intervention and management strategies in
      health care institutions may, therefore, need to be modified in order to deal
      with violence. An examination of the data allows development of a profile for
      violence in medical settings and the identification of risk factors. Security
      issues for hospitals, clinics, and physician offices are also discussed.

PMID- 9149495
TI  - Alzheimer's disease: new horizons in diagnosis and treatment.
AB  - We are in the midst of an explosion in research in Alzheimer's disease. Advances
      in our scientific understanding of genetic factors and pathogenesis are leading
      to enhanced diagnostic capabilities and new presymptomatic and symptomatic
      therapies. Estrogen therapy in postmenopausal females and NSAIDs show early
      promise, while AChE inhibitors keep getting better. Armed with knowledge and new
      diagnostic and therapeutic tools, we can finally begin to fight this devastating
      disease.

PMID- 9149498
TI  - Wilms' tumor in an adult: a case report and review of the literature.
AB  - Wilms' tumor in an adult is extremely rare, with less than 250 cases reported in
      the world literature. Treatment guidelines for pediatric Wilms' tumor are well
      established; those for adults are not. This article presents the case of a 19
      year-old male diagnosed with Wilms' tumor after complaints of hematuria. He was
      categorized as Stage IV after nephrectomy and received post-operative
      radiotherapy and chemotherapy consisting of Vincristine, Adriamycin, and
      Actinomycin-D. Two years later he was found to have metastases to brain and
      lungs. He was treated with radiotherapy and bone marrow transplantation, and died
      of septic shock. The literature regarding Wilms' tumor in adults is reviewed, and
      current therapy is discussed.

PMID- 9149500
TI  - Disclosure, hearsay and previous misconduct--progress in the criminal law?

PMID- 9149499
TI  - Tuberculous lymphadenitis in the adult.

PMID- 9149501
TI  - The future of disclosure, hearsay and evidence of defendants' previous misconduct
      in criminal proceedings in England and Wales. The seventh veil.

PMID- 9149502
TI  - Disclosure: the role of the Crown Prosecution Service.

PMID- 9149503
TI  - Criminal Procedure and Investigations Act 1996.

PMID- 9149504
TI  - Disclosure: the defence perspective.

PMID- 9149505
TI  - Third party disclosure: public interest immunity.

PMID- 9149506
TI  - The Law Commission's work on hearsay and previous misconduct.

PMID- 9149507
TI  - The Law Commission's previous misconduct and hearsay proposals--a practitioner's
      response.

PMID- 9149508
TI  - Rubber and plastic ammunition lethal injuries: the Israeli experience.
AB  - Rubber and plastic ammunition was used by the Israeli Defence Forces between the
      years 1987 and 1993 (Intifada) almost exclusively as a deterrent to aggression by
      the Palestinian civilian population in the occupied territories of Gaza, Judea
      and Samaria. While designed to avoid the serious wounds and deaths caused by the
      use of conventional military ammunition, the firing of rubber and plastic bullets
      has resulted in extensive injuries and more than 20 deaths. The data from the
      autopsies of 17 of these victims, mostly teenagers, were analysed. Ten of the
      victims died from injuries inflicted by Improved Rubber Bullets, while the other
      seven succumbed to injuries caused by Plastic Bullets. In most instances, the
      cause of death was related to injuries to the brain. Ballistic features of non
      conventional bullets are discussed, and suggestions to curtail the serious
      injuries and fatalities arising from their use are given, with emphasis on firing
      from a safe range. British and South African experience with this type of
      ammunition is compared with our observations.

PMID- 9149509
TI  - Physical restraint of patients in a psychiatric hospital.
AB  - Use of physical restraint occurs within British psychiatric hospitals yet there
      has been little evaluative research on current practice. The present study aims
      to describe a group of disturbed in-patients who had required physical restraint
      at some point during the course of their stay in hospital and to classify the
      reasons for its use. Cases were identified using Case Register data and
      information obtained from patients' records. In the 48 episodes of physical
      restraint identified, patients were predominantly schizophrenic (60%), male (67%)
      and had been restrained because of physical violence to others (44%) or because
      they were attempting to abscond (31%). Although the majority of patients were
      compulsorily detained prior to the use of physical restraint, three remained
      informal. The findings are discussed in the context of the legal justifications
      for use of restraint. Further research on current practice is required to enable
      formulation of clear guidelines.

PMID- 9149511
TI  - Assessment of the perceived need for a psychiatric service to a magistrates'
      court.
AB  - One approach to diversion from custody of mentally disordered offenders is to
      provide a psychiatric liaison service to local magistrates' courts. We aimed to
      establish whether such a scheme was needed locally. Questionnaires for the bench,
      defence solicitors and bail information officers, enquiring as to the perceived
      need for a psychiatric assessment, social service care and specialist bail
      provision, were distributed for all those appearing in a magistrates' court who
      had been held overnight in police custody. Responses were received for 223
      individuals. An immediate psychiatric report was considered necessary for 4.9% of
      cases. In 2.2% of cases it was thought that remand in custody could have been
      avoided if such an opinion had been available. In 8% of cases it was thought that
      remand in custody could have been avoided if specialist bail provision were
      available. We conclude that availability of a specialist bail provision would
      lead to a greater number of diversions from custody than providing a psychiatric
      service to this magistrates' court.

PMID- 9149510
TI  - Repetitive and non-repetitive violent offending behaviour in male patients in a
      maximum security mental hospital--clinical and neuroimaging findings.
AB  - OBJECTIVE: To examine if different violent offending behaviours are associated
      with different clinical and neuroimaging profiles. METHOD: Thirty-nine
      schizophrenic and schizoaffective offenders from a maximum security mental
      hospital-20 repetitive violent offenders (RVOs) and 19 non-repetitive violent
      offenders (NRVOs)-were selected for clinical and neuroimaging assessments.
      RESULTS: Both groups had positive family history of mental illness and violence.
      Age, diagnosis, duration of illness, victim profiles and use of weapons at the
      time of the index offence were similar. RVOs had a higher prevalence of early
      parental separation, juvenile conduct problem, previous convictions of crimes not
      involving violence, impulsive suicide attempts, delusion of their lives being
      threatened at the time of the index offence and electroencephalographic (EEG)
      abnormalities localized to temporal lobes. NRVOs had a higher prevalence of
      sexual inexperience and command hallucinations to kill at the time of the index
      offence. Asymmetric gyral patterns at the temporo-parietal region were
      particularly common in RVOs and absent in NRVOs. Non-specific white matter
      changes in magnetic resonance imaging (MRI) and generalized cortical
      hypometabolism in positron emission tomography (PET) were present in both groups.
      CONCLUSIONS: Different structural and metabolic changes in the brain were
      associated with different violent offending behaviours. The complex interaction
      between violent behaviour, clinical features and neuroimaging findings in
      schizophrenia requires further studies.

PMID- 9149513
TI  - Sudden unexplained death in a psychiatric patient--a case report: the role of
      phenothiazines and physical restraint.
AB  - Psychotropic drug use has long been associated with sudden unexplained and
      unexpected death in psychiatric patients despite controversies surrounding the
      issue. Physical restraint following violent episodes in psychiatric in-patients
      is also associated with neurally mediated sudden cardiac death. A case where
      these two mechanisms have jointly resulted in sudden death is reported. The
      literature on the subject is reviewed and the measures which may be useful in
      reducing the incidence of such deaths are discussed. The need for accurate and
      detailed reporting of such cases is emphasized.

PMID- 9149512
TI  - Gender-based differences in the treatment of young offenders by the police and
      the children's court in New South Wales, Australia.
AB  - It has been consistently reported that young males commit crimes with an average
      frequency five times greater than their female peers. Most data supporting this
      view are derived from juvenile court and police statistics. Studies using data
      derived from self-reported behaviour suggest that the true relative frequency may
      be closer to 2:1. Police and juvenile justice data for the year 1994-5 in New
      South Wales, Australia, were analysed in an attempt to determine whether court
      and police statistics might reflect a form of selection bias, where the
      likelihood of arrest, trial and/or sentence is a function of gender, rather than
      frequency and nature of offence. The results suggest that the 5:1 gender ratio
      reflects a strong component of gender bias in the workings of the juvenile
      justice system in New South Wales. If suspected of a given crime, young males are
      more likely to be denied bail and (if found guilty) to be given a harsher
      sentence than young females suspected (or found guilty) of the same crime.
      Overall, if found guilty of an offence, boys were four times more likely than
      girls to receive a custodial sentence. Therefore, boys are selectively denied
      access to alternate rehabilitation resources which are made available to girls
      who are in trouble with the law. The juvenile justice system in New South Wales
      requires careful examination and reform if such apparently deeply entrenched
      biases are to be eliminated.

PMID- 9149514
TI  - Self-mutilation with needles.
AB  - Two cases of self-mutilation with needles are reported. One of the deceased
      suffered from chronic schizophrenia and committed suicide by plastic bag
      suffocation. At autopsy several needles were detected grown into the connective
      tissue of chest or abdominal organs. In the other case a knitting needle was used
      for repeated manipulations at the forehead leading to a defect of the skin and
      the skull. At least one vessel was injured leading to an extensive haemorrhage in
      the left hemisphere of the brain. The forensic and etiologic aspects of the cases
      are discussed.

PMID- 9149515
TI  - Catalytic converter and suicide risk revisited.

PMID- 9149516
TI  - Inadequacies in the Mental Health Act 1983 in relation to mentally disordered
      remand prisoners.

PMID- 9149517
TI  - When is a match not a genetic match?

PMID- 9149518
TI  - The Mental Health Act and professional hostage taking.

PMID- 9149519
TI  - Displacement of the nearest relative.

PMID- 9149520
TI  - The reform of civil justice and its effect on medical negligence litigation.

PMID- 9149521
TI  - Presidential address. The Medico-Legal Society.

PMID- 9149523
TI  - The role of the peridomiciliary area in the elimination of Triatoma infestans
      from rural Argentine communities.
AB  - The purpose of this study was to identify the origin of Triatoma infestans
      reinfestation and study its dynamics following spraying with deltamethrin inside
      and around 94 houses in three rural communities in northwestern Argentina. The
      effectiveness of the spraying was evaluated immediately after the houses were
      sprayed and two months later. In addition, five residual peridomiciliary foci
      were found and sprayed, as well as three preexisting ones that had not been
      sprayed. To monitor reinfestation, biosensors were placed in the houses and each
      family was also asked to capture triatomines and keep them in plastic bags; in
      addition, triatomines were searched for in and around houses, using an aerosol
      that dislodged them from their hiding places. Selective sprayings were carried
      out only where a colony of T. infestans was found. During the 30 months of follow
      up, the percentage of houses in which any T. infestans were captured varied
      between 3% and 9%. In six houses, T. infestans were captured during more than one
      evaluation. The number of peridomiciliary areas found to be infested (19) was
      double the number of infested houses (9). Colonies of T. infestans were found
      only in the peridomiciliary areas, where the number of T. infestans captured was
      six times higher than in the houses. Chickens were the host most frequently
      associated with peridomiciliary foci. This area was the origin and principal
      source of reinfestation. To reduce the speed of reinfestation and the frequency
      with which sprayings are needed, the following environmental and chemical control
      methods must be combined in the peridomiciliary area: reduce the number of hiding
      places of triatomines; restrict the raising of birds to structures that cannot be
      colonized by triatomines; apply an insecticide that is less likely to be degraded
      by exposure to the elements, or perform a second spraying 6 to 12 months after
      the first; and employ a device for early detection of the presence of T.
      infestans around houses.

PMID- 9149525
TI  - Cervical cancer: summary of the NIH consensus.

PMID- 9149524
TI  - Factors favoring houseplant container infestation with Aedes aegypti larvae in
      Marilia, Sao Paulo, Brazil.
AB  - Since reinvasion of Sao Paulo State by the Aedes aegypti (L.) mosquito in 1985,
      flower pots and vases have been important larval habitats despite educational
      messages focusing on their control. The objectives of this study were to
      characterize flower pots and vases as larval habitats with respect to the
      quantities present and infested, the types of plants involved, and the specific
      locations of the mosquito larvae; to explore local names for houseplants; and to
      examine factors affecting acceptance of control measures. The results showed an
      average of more than four potential plant-related larval habitats per premises,
      of which only 0.4% were occupied by the vector. Plant-related containers
      represented 31% of all the containers with Aedes aegypti larvae. Although a
      sample of 126 respondents was able to list 105 different houseplant names, 49% of
      the positive plants were of two types: ferns and the ornamental plant
      Dieffenbachia avoena. The public's apparent unwillingness to accept recommended
      anti-aegypti control measures involving houseplants seems related to the relative
      rarity of aegypti larvae in the very common houseplant containers, the control
      program's poor credibility as a source of information about plants, and a
      perception that the recommended control measures are harmful to plants. An
      intervention currently being planned for dengue control will use educational
      material that refers specifically to those plants whose containers are most
      commonly found to harbor aegypti larvae; it will also utilize information sources
      such as botanists with greater credibility regarding plants; and it will set out
      alternative plant care recommendations that are more likely to appeal as
      beneficial to the plants and that will stand a better chance of being accepted.

PMID- 9149526
TI  - Cell death induction by TNF: a matter of self control.

PMID- 9149527
TI  - Highways for protein delivery to the mitochondria.
AB  - Messenger RNA (mRNA) localisation is one of the prime mechanisms to ensure
      protein localisation in the cytoplasm of polarised embryonic cells, and has been
      well-studied in the development of Xenopus and Drosophila embryos. But what of
      other cells? Here, we discuss whether the directed transport of mRNA out of the
      nucleus, following cytoplasmic highways to a specified organelle in the
      cytoplasm, might also contribute to the exquisite fidelity of protein targeting
      observed in all eukaryotic cells.

PMID- 9149528
TI  - Does HIV tat protein also regulate genes of other viruses present in HIV
      infection?

PMID- 9149529
TI  - Enzyme HIT.

PMID- 9149530
TI  - ATP-dependent proteases that also chaperone protein biogenesis.
AB  - The ATP-dependent proteases Clp and FtsH from bacteria, as well as mitochondrial
      homologs of FtsH and Lon from yeast, may act as chaperones; they mediate not only
      proteolysis, but also the insertion of proteins into membranes and the
      disassembly or oligomerization of protein complexes. The coordination of such
      processes with selective proteolysis may function in the quality control of
      protein biogenesis.

PMID- 9149531
TI  - Silencers and locus control regions: opposite sides of the same coin.
AB  - Whether or not genes are in an active or a repressed state in a cell depends on
      the relative effect of gene silencers and locus control regions (LCRs). Here, we
      suggest that these elements act as binary switches; the state that prevails
      (activated or repressed) probably depends on a competition between protein
      complex formation and the stability of the complexes formed at either of the two
      elements.

PMID- 9149532
TI  - Histone acetylation: chromatin in action.
AB  - Histone acetylation acts as a landmark and determinant for chromatin function.
      Active roles in the transcription and assembly of chromatin have been discovered
      for histone acetyltransferases and deacetylases. This review highlights these
      roles and discusses their significance for the maintenance of cell
      differentiation.

PMID- 9149533
TI  - Pre-mRNA splicing: the discovery of a new spliceosome doubles the challenge.
AB  - A rare class of pre-mRNA introns with non-canonical consensus sequences has been
      identified in metazoan genes. The novel, low-abundance spliceosome that excises
      these introns contains one small nuclear ribonucleoprotein (snRNP) in common with
      the major spliceosome (U5) and four snRNPs that are distinct from, but
      structurally and functionally analogous to U1, U2 and U4-U6. The architecture of
      RNA components at the presumptive core of the AT-AC splicesome supports current
      models of the spliceosomal active center and raises tantalizing questions about
      spliceosome evolution.

PMID- 9149534
TI  - Methods and reagents. Degraded DNA and gel tornados.
AB  - Methods and reagents is a unique monthly column that highlights current
      discussions in the newsgroup bionet.molbio.methds-reagnts, available on the
      Internet. This month's column discusses a case of inexplicable DNA degradation
      and tornados seen in agarose gels. For details on how to partake in the
      newsgroup, see the accompanying box.

PMID- 9149535
TI  - Who uses CD-ROMs in the information age?

PMID- 9149536
TI  - Metabotropic GABA(B) receptors cloned at last.

PMID- 9149537
TI  - The 5-HT7 receptor: orphan found.

PMID- 9149538
TI  - A Ca2+ release mechanism gated by the novel pyridine nucleotide, NAADP.

PMID- 9149539
TI  - Knowledge and skills needs of pharmacology graduates in first employment: how do
      pharmacology courses measure up?

PMID- 9149540
TI  - Eosinophil lysis and free granules: an in vivo paradigm for cell activation and
      drug development.
AB  - Release of cytotoxic granule proteins from activated eosinophil granules is
      considered to be a key pathogenic mechanism in eosinophilic diseases. Degenerated
      eosinophils and extracellular eosinophil granules have been repeatedly depicted.
      The present overview describes evidence that eosinophil lysis and distribution of
      free eosinophil granules (as opposed to 'classical degranulation') is an
      important mechanism by which eosinophils affect their surroundings. Here, Carl
      Persson and Jonas Erjefalt summarize how recent reports on the induction of
      eosinophil lysis in vivo provide a new paradigm for eosinophil activation and
      thus constitute a novel basis for pharmacological manipulations in eosinophilic
      diseases.

PMID- 9149541
TI  - Calcineurin regulation of synaptic function: from ion channels to transmitter
      release and gene transcription.
AB  - Calcineurin is a calcium (Ca2+)/calmodulin (CaM)-dependent protein phosphatase
      that has been shown to regulate the activity of ion channels, neurotransmitter
      and hormone release, synaptic plasticity and gene transcription. At glutamatergic
      synapses, the inhibition of calcineurin with immunosuppressant drugs has been
      reported to enhance both the presynaptic release of glutamate and postsynaptic
      responsiveness. Several other ligand- and voltage-gated ion channels are
      negatively regulated by calcineurin. Hormone release in insulin-secreting
      pancreatic beta cells and pituitary corticotrope tumour (AtT20) cells is also
      negatively regulated by calcineurin. In this article, Jerrel Yakel discusses the
      evidence that calcineurin plays a vital role in regulating neuronal excitability
      and hormone release.

PMID- 9149542
TI  - Where is the locus in opioid withdrawal?
AB  - Identification of neuroadaptations in specific brain regions that generate
      withdrawal is crucial for understanding and perhaps treating opioid dependence.
      It has been widely proposed that the locus coeruleus (LC) is the nucleus that
      plays the primary causal role in the expression of the opioid withdrawal
      syndrome. MacDonald Christie, John Williams, Peregrine Osborne and Clare
      Bellchambers believe that this view and the interpretation of the literature on
      which it is based are at best controversial. Here, they suggest an alternative
      view in which regions close to the LC such as the periaqueductal grey, as well as
      other brain structures which are independent of the LC noradrenergic system, play
      a more important role in the expression of the opioid withdrawal syndrome.

PMID- 9149543
TI  - The health care ethics consultant and beneficence in medicine.

PMID- 9149544
TI  - Epidemiology of Helicobacter pylori infection in Barbados.
AB  - The epidemiology of Helicobacter pylori infection in Barbadian patients and
      controls was studied. H. pylori was isolated from biopsies from 50/100 (50%)
      adult patients undergoing endoscopy for investigation of upper gastrointestinal
      tract symptoms. Urease was detected in biopsies from 54 patients and gastritis
      was detected by histology in 71 patients. Serology was performed using a
      commercial ELISA method. Using an IgG concentration of 10 U/ml as a threshold,
      antibodies were detected in 78% of 100 patients undergoing endoscopy, 72% of 230
      blood donors and 22% of 50 children. The mean antibody concentration was
      significantly higher in patients (92 U/ml) than in blood donors (49 U/ml) or in
      children (9.5 U/ml). Culture-positive patients (120 U/ml) had higher IgG
      concentrations than culture-negative patients (64 U/ml). Using isolation of H.
      pylori or a positive biopsy urease test as a measure of true prevalence of
      infection, the sensitivity of serology was 96%, the specificity 42%, positive
      predictive value 67% and negative predictive value 90%. Seroprevalence increased
      with age, to a peak of more than 90% in blood donors aged 50-59 years and in
      patients aged over 60 years. The epidemiology of H. pylori in Barbados is similar
      to that in developed countries, where few children are infected, but resembles
      other developing countries in the high seroprevalence observed in middle-aged
      adults. Our results confirm the utility of serology for detecting H. pylori by a
      non-invasive technique.

PMID- 9149545
TI  - Lifestyle in Curacao. Smoking, alcohol consumption, eating habits and exercise.
AB  - The Curacao Health Study was carried out among a randomized sample (n = 2248,
      response rate = 85%) of the adult non-institutionalized population in order to
      assess aspects of lifestyle that may pose health risks. Factors examined were
      tobacco and alcohol use, eating habits and exercise behaviour. Outcome variables
      were cross-tabulated by gender, age and socioeconomic status. 17.1% of the
      participants were smokers and 20.5% were regular drinkers, including 6.3% of the
      men who consumed alcohol excessively (4 or more glasses of alcohol a day). 75% of
      the participants did not exercise regularly, 37% did not eat vegetables daily,
      and half did not eat fruit daily. Other poor eating habits were the addition of
      extra sugar and salt to prepared food by 33% and 20% of the participants,
      respectively. On the whole, men had less healthy lifestyles than women, with the
      exception of exercise behaviour. People of high socioeconomic status (SES) drank
      less alcohol, and exercised more often than those of low SES. Considering the
      high prevalence of diabetes mellitus and hypertension in the Caribbean, research
      on lifestyle factors in other Caribbean countries is required to facilitate the
      development of regional prevention and intervention programmes.

PMID- 9149546
TI  - Scanning electron microscopy of the jejunum in children with protein-energy
      malnutrition.
AB  - Samples of jejunum from seven children dying from severe oedematous malnutrition
      were fixed with intralumenal glutaraldehyde in combination with external
      immersion, using a rapid autopsy protocol. Selected areas were post-fixed in
      osmium tetroxide, dehydrated with an ethanol series and critical point dried.
      After mounting on aluminium stubs, specimens were sputter-coated with a thin
      layer of gold and palladium. Scanning electron microscopy showed patterns ranging
      from subtotal villous atrophy, through partial villous atrophy with low ridges,
      to longer, taller ridges with cerebriform convolutions. In one case, villous
      height had been interpreted as normal on light microscopy. The scanning electron
      microscope revealed that the mucosa in this case was composed of ridges and leaf
      forms. Processing for scanning electron microscopy is simple. The specimens can
      be viewed and photographed in a relatively short time. In addition, the three
      dimensional record provides clarification of ambiguities which often arise from
      routine histological sections.

PMID- 9149547
TI  - Kidney function in phasic insulin dependent diabetes mellitus in Jamaica.
AB  - In Jamaica, malnutrition related diabetes mellitus (MRDM) presents the clinical
      picture of phasic insulin dependence. This study was undertaken to investigate
      nephropathic changes associated with this group of patients. Fourteen phasic
      insulin dependent diabetes mellitus (PIDDM) patients were compared with 10
      insulin dependent (IDDM) and 10 non-insulin dependent (NIDDM) diabetes mellitus
      patients, and 10 normal controls. Each group was matched for age, sex, body mass
      index (BMI) and, in the case of the diabetic patient controls, duration of
      diabetes. Urinary microalbumin concentration was significantly (p < 0.05) higher
      in the PIDDM group (mean +/- SD: 153 +/- 48.3 mg/dl) than in the groups of NIDDM
      (35.7 +/- 9.6 mg/dl) or IDDM (38.6 +/- 15.8 mg/dl) patients. Serum urea and
      creatinine concentrations (mean +/- SE 7.6 +/- 1.0 mmol/l and 130.0 +/- 20.3
      mumol/l, respectively) were higher in the PIDDM patients than in the NIDDM and
      IDDM groups. Confounding factors such as hypertension and urinary tract
      infections were excluded as causes for these differences. We conclude that PIDDM
      patients have more severe renal dysfunction than NIDDM patients and, since
      glycosylated haemoglobin concentrations are comparable in these groups, we
      attribute this to a renal insult due to malnutrition predating the onset of the
      PIDDM.

PMID- 9149548
TI  - Invasive streptococcal infections. Report of four cases occurring in Trinidad.
AB  - Many countries are reporting a resurgence of virulent streptococcal strains but
      there is little information from the Caribbean. Four cases of severe invasive
      streptococcal infections, three of them fatal, are reported. The portal of entry
      was infected scabatic lesions in one patient and infected mosquito bites in
      another patient who developed cellulitis and gangrene; but no portal of entry was
      detected in the other patients. Group A beta haemolytic Streptococcus (GAS) was
      isolated from the blood of three patients, one of them GAS M type 3, which had
      the genome for streptococcal pyrogenic exotoxins A (SPeA) and B (SPeB). GAS M
      type 72, which had the genome for SPeB and SPeC, were isolated from the tissues
      (but not from the blood) of the patient who developed cellulitis and who was the
      sole survivor. Physicians in the Caribbean must be alerted to the presence of
      these virulent streptococcal strains, and must be prepared to manage serious
      invasive disease.

PMID- 9149549
TI  - Cardiac fibroma presenting as sudden death in a six-month-old infant.
AB  - Cardiac fibroma is a rare benign tumour which occurs predominantly in infancy and
      childhood. We present the case of a six-month-old female infant who died suddenly
      at home and was found at autopsy to have a large cardiac fibroma in the
      ventricular septum. The tumour was apparently asymptomatic although there was
      evidence of mild cardiac failure. Death was thought to be due to a fatal
      arrhythmia.

PMID- 9149550
TI  - The 'internal clocks' of circadian and interval timing.
AB  - Animals engage in a startlingly diverse array of behaviours that depend
      critically on the time of day or the ability to time short intervals. Timing
      intervals on the scale of many hours to around a day is mediated by the circadian
      timing system, while in the range of seconds to hours a different system, known
      as interval timing, is used. Recent research has illuminated some of the neural
      mechanisms underlying the 'internal clocks' of these two different timing systems
      in both animals and humans. Therapeutic applications for humans with impairments
      in either timing system may ultimately result from these endeavours.

PMID- 9149551
TI  - Stable isotope methods for studying nutrient mineral metabolism in humans.
AB  - Stable isotopes are safe, versatile, scientifically rigorous tools for studying
      nutrient metabolism in humans. They can be used to follow the metabolism of
      nutrient minerals from specific foods or diets, including the determination of
      efficiency of absorption and the effects of dietary constituents on absorption,
      and to investigate fundamental aspects of nutritional biochemistry. In this
      article we describe stable isotope methods and the results of some recent
      nutrient mineral metabolism studies in humans.

PMID- 9149552
TI  - Alternative forms of the critical power test for ramp exercise.
AB  - The critical power test provides estimates of two important parameters
      characterizing work performance; anaerobic work capacity (AWC) and critical power
      (CP). The CP concept has recently been adapted to a test procedure involving ramp
      exercise. Just as the constant power format of the CP test can be expressed in
      several mathematically equivalent forms, so too can the ramp format. This
      communication illustrates these forms and tests the various AWC and CP estimates
      so obtained. It is found that three of the four forms provide equivalent
      estimates for both AWC and CP. It is concluded that provided either endurance
      time or total work performed is taken as the dependent variable, researchers can
      expect consistent estimates for both AWC and CP.

PMID- 9149553
TI  - Physiological model of CO2 output during incremental exercise.
AB  - In this study, a physiological model to explain the pathway of CO2 output during
      incremental exercise was examined by referring to experimental data. Since CO2
      output (VCO2) shows multiple correlations with mixed venous CO2 pressure (PvCO2)
      and arterial CO2 pressure (PaCO2), the increase in the difference between PvCO2
      and PaCO2 was considered to be involved in the increase in VCO2. In order to
      better understand the influence of CO2 pressure, VCO2 was divided into the
      expiratory CO2 phase (non-lactic VCO2), which was unrelated to lactic acid
      increase and the expiratory CO2 phase (excess VCO2), which was related to lactic
      acid increase. As a result, the non-lactic VCO2 significantly correlated to
      PvCO2. When non-lactic VCO2 was zero, the value of PvCO2 was 43.7 mmHg. This was
      higher than the resting PaCO2 value. On the other hand, as PaCO2 showed an almost
      constant value in the low load phase and showed a low value in the high load
      phase, it was believed that the low value of PaCO2 was related to the excess VCO2
      that appeared in the high load phase. The CO2 excess, which was obtained by
      adding excess VCO2 in terms of the lapse of exercise time, correlated
      significantly with an increase in lactate in the blood. Based on the results, a
      model was constructed to illustrate the pathway of CO2 output. The key points of
      the model were as follows: (1) the use of the blood CO2 dissociation curve as the
      vector to transport CO2 from tissue to lungs, (2) the standard value of PaCO2 was
      established in order to divide non-lactic VCO2 and excess VCO2, (3) the
      dextroversion of the blood CO2 dissociation curve due to lactic acid was
      connected to excess VCO2, and (4) a decrease in PaCO2 was related to excess VCO2
      derived from tissue.

PMID- 9149555
TI  - Load knowledge affects low-back loading and control of balance in lifting tasks.
AB  - This study investigated the effect of the presence or absence of load knowledge
      on the low-back loading and the control of balance in lifting tasks. Low-back
      loading was quantified by the net sagittal plane torque at the lumbo-sacral
      joint. The control of balance was studied by the position of the centre of
      gravity relative to the base of support, the horizontal and vertical momentum of
      the centre of gravity and the angular momentum of the whole body. In a first
      experiment, 8 male subjects lifted a rather heavy load (22% of body mass), using
      a leglift and a backlift, while they were familiar with the load mass. To
      counteract the threat to balance, imposed by picking up a load in front of the
      body, the subjects performed specific preparations, based upon the known load
      mass; prior to load pick-up, profound changes in the horizontal and angular
      momentum were found. The preparations were technique specific. Preserving balance
      seemed easier while picking up a load with a backlift than with a leglift. In the
      second experiment, 25 male subjects lifted a 6 kg box, which they expected to be
      16 kg, because, in a series of lifts, the load mass was changed from 16 to 6 kg
      without their knowledge. Despite the 10 kg difference in actual load mass, the
      net torque at the lumbo-sacral joint was not different between lifting 6 and 16
      kg, until 150 ms after box lift-off. Moreover, lifting of the overestimated load
      mass caused a disturbance of balance in 92% of the trials. The postural reactions
      aimed at regaining balance were not accompanied by an increased low-back loading.
      It was concluded that the absence of load knowledge, and the following
      overestimation of the load mass to be lifted, lead to an increased mechanical
      load on the lumbar spine and to an increased risk of losing balance in lifting
      tasks. Both events may contribute to a higher risk of low-back injury in manual
      materials handling tasks.

PMID- 9149554
TI  - A single metric for quantifying biomechanical stress in repetitive motions and
      exertions.
AB  - The relative effects of repetition, force and posture were studied in order to
      investigate how continuous biomechanical measurements can be combined into a
      single metric corresponding to subjective discomfort. A full factorial experiment
      was conducted involving repetitive wrist flexion from a neutral posture to a
      given angle against a controlled force. Seven subjects performed the task using
      two paces (20 and 4 motions/min), two force levels (15 and 45 N) and two angles
      (15 and 45 degrees) for 1 h each. Discomfort was reported on a 10 cm visual
      analogue scale anchored between 'no discomfort' and 'very high discomfort'.
      Repeated measures analysis of variance showed that all main effects were
      statistically significant (p < 0.05) and no significant interactions were
      observed. A linear regression model was fitted to the data and used for
      generating frequency weighted digital filters that shape continuous recordings of
      repetitive motions and exertions into an output proportional to relative
      discomfort. The resulting high-pass digital filter had a 22 dB/decade attenuation
      slope. A simulated industrial task used for validating the model involved
      repetitively transferring pegs across a horizontal bar and inserting them into
      holes against a controlled resistance. Angular wrist data were recorded using an
      electrogoniometer and filtered. Six subjects performed the task of the three
      conditions consisting of (1) 15 wrist flexion, 15 N resistance and 6 motions min,
      (2) 15 wrist flexion. 45 N resistance and 12 motions/min, and (3) 45 degrees
      wrist flexion, 45 N resistance and 15 motions/min. Subjective discomfort was
      reported after performing the task for 1 h. Pearson correlations between
      subjective discomfort ratings and the integrated filtered biomechanical data for
      individual subjects ranged from 0.90 to 1.00. The pooled correlation across
      subjects was 0.67. This approach may be useful for physical stress exposure
      assessment and for design of tasks involving repetitive motions and exertions.

PMID- 9149556
TI  - Isometric muscle strength of Chinese young males in Taiwan.
AB  - This paper represents the results of an anthropometric measurement of the
      isometric muscle strength of Chinese young males in Taiwan aged from 16 to 20
      years. The study uses a sample of 120 male students and measures four types of
      muscle strength: (1) right arm strength in exerting pull, push, adduction,
      abduction, lift, and press directions with five elbow angles (60, 90, 120, 150
      and 180 degrees) in seated posture; (2) grip strength of both hands; (3) backlift
      strength: and (4) chest expanding strength. The obtained data are analysed and
      listed. Comparisons are made between the results of this study and those from
      domestic and foreign studies available in the literature. In general, their
      pattern is similar, but values obtained in this study are relatively smaller than
      those obtained in western countries.

PMID- 9149557
TI  - 'Multidrug'-resistant tuberculosis. It is time to focus on the private sector of
      medicine.

PMID- 9149558
TI  - Beyond directly observed therapy for tuberculosis.

PMID- 9149559
TI  - From magic mountains to modern times. A view from the community hospital.

PMID- 9149560
TI  - Respiratory drug delivery.

PMID- 9149561
TI  - Diagnostic interpretation of pericardial fluids.

PMID- 9149562
TI  - Why does lactic acidosis occur in acute lung injury?

PMID- 9149563
TI  - Strategies for treatment of occult carcinomas of the endobronchus.

PMID- 9149564
TI  - Retreatment tuberculosis cases. Factors associated with drug resistance and
      adverse outcomes.
AB  - STUDY OBJECTIVE: Risk factors associated with treatment failure and multidrug
      resistant tuberculosis (MDR-TB) were examined among HIV-seronegative patients who
      were previously treated for tuberculosis (TB). DESIGN: Prospective, cohort study
      of patients referred to the study hospital for retreatment of TB between March
      1986 and March 1990. PATIENTS: The patients belonged to three groups, according
      to outcomes following their previous treatment: 37 patients who abandoned
      treatment or suffered relapse after completion of therapy (group A), 91 patients
      who failed to respond to the first-line drug regimen (group B), and 78 patients
      who failed to respond to the second-line drug regimen (group C). RESULTS:
      Patients with Mycobacterium tuberculosis strains resistant to rifampin and
      isoniazid were found in 2 (6%) in group A, 29 (33%) in group B, and 49 (65%) in
      group C. Cure was achieved in 77% in group A, 54% in group B, and 36% in group C.
      Death occurred in none of the patients in group A, 8% in group B, and 24% in
      group C. In a multivariate logistic regression analysis, unfavorable response
      (failure to sterilize sputum culture, death, and abandonment) was significantly
      associated with infection with a multidrug-resistant M tuberculosis strain (p =
      0.0002), cavitary disease (p = 0.0029), or irregular use of medications (p <
      0.0001). CONCLUSIONS: These observations show that a previous treatment outcome
      and current clinical and epidemiologic histories can be used to predict the
      development of MDR-TB and adverse outcomes in patients undergoing retreatment for
      TB. Such information may be useful for identifying appropriate patient candidates
      for programs such as directly observed therapy.

PMID- 9149565
TI  - Noncompliance with directly observed therapy for tuberculosis. Epidemiology and
      effect on the outcome of treatment.
AB  - STUDY OBJECTIVES: To describe the epidemiology and clinical consequences of
      noncompliance with directly observed therapy (DOT) for treatment of tuberculosis.
      DESIGN: Retrospective review. SETTING: An urban tuberculosis control program that
      emphasizes DOT. PATIENTS: All patients treated with outpatient DOT from 1984 to
      1994. MEASUREMENTS AND RESULTS: We defined noncompliance as follows: (1) missing
      > or = 2 consecutive weeks of DOT; (2) prolongation of treatment > 30 days due to
      sporadic missed doses; or (3) incarceration for presenting a threat to public
      health. Poor outcomes of therapy were defined as a microbiologic or clinical
      failure of initial therapy, relapse, or death due to tuberculosis. Fifty-two of
      294 patients (18%) who received outpatient DOT fulfilled one or more criteria for
      noncompliance. Using multivariate logistic regression, risk factors for
      noncompliance were alcohol abuse (odds ratio, 3.0; 95% confidence interval, 1.2
      to 7.5; p = 0.02) and homelessness (odds ratio, 3.2; 95% confidence interval, 1.5
      to 7.2; p = 0.004). Noncompliant patients had poor outcomes from the initial
      course of therapy more often than compliant patients: 17 of 52 (32.7%) vs 8 of
      242 (3.3%); relative risk was 9.9; 95% confidence interval was 4.5 to 21.7 (p <
      0.001). CONCLUSIONS: In an urban tuberculosis control program, noncompliance with
      DOT was common and was closely associated with alcoholism and homelessness.
      Noncompliance was associated with a 10-fold increase in the occurrence of poor
      outcomes from treatment and accounted for most treatment failures. Innovative
      programs are needed to deal with alcoholism and homelessness in patients with
      tuberculosis.

PMID- 9149566
TI  - The utility of a single sputum specimen in the diagnosis of tuberculosis.
      Comparison between HIV-infected and non-HIV-infected patients.
AB  - STUDY OBJECTIVES: (1) To assess the utility of a single sputum specimen in the
      evaluation of HIV-infected patients who are suspected of having tuberculosis
      (TB). (2) To identify radiographic findings that discriminate between HIV
      infected patients with TB and those with pneumonia of other causes. DESIGN:
      Retrospective cohort analysis. PATIENTS: All patients evaluated at Harborview
      Medical Center, Seattle, between January 1986 and July 1994 in whom culture of
      respiratory secretions grew Mycobacterium tuberculosis or Mycobacterium avium
      complex. Patients who were coinfected with HIV formed the primary study group.
      Their chest radiographs were then compared with those of a matched group of
      patients with pneumonia of other causes. MEASUREMENTS AND RESULTS: We identified
      164 patients with TB, 20 of whom were HIV infected. The initial sputum specimen
      grew M tuberculosis in all HIV-infected patients and 99% of non-HIV-infected
      patients. Seventy percent of HIV-infected and 71% of non-HIV-infected patients
      had at least one positive smear. Most of these patients tested positive on their
      initial smear, and no significant difference was found between HIV-positive and
      HIV-negative patients (79% and 90%, respectively [p = 0.34]). The addition of a
      second sputum smear identified all HIV-infected patients and all but one in non
      HIV-infected patients who were ultimately determined to be smear positive. A
      total of 27 HIV-infected patients had a positive acid-fast bacilli sputum smear
      during the study period, 14 of which were attributable to TB (specificity = 52%).
      The only radiographic findings that discriminated between HIV-infected patients
      with TB and those with pneumonia of other causes were the presence of cavitation
      or a miliary pattern (p = 0.014). CONCLUSIONS: A single sputum specimen was
      sufficient to establish the diagnosis in all HIV-infected patients with pulmonary
      TB. A single negative sputum smear made the diagnosis of TB significantly less
      likely. However, a minimum of two smears were necessary to achieve an acceptable
      early diagnostic yield. The presenting chest radiograph failed to discriminate
      between HIV-infected patients with TB and pneumonia of other causes in most
      cases.

PMID- 9149567
TI  - Empiric treatments impair the diagnostic yield of BAL in HIV-positive patients.
AB  - OBJECTIVE: To investigate the influence of empiric treatments prior to fiberoptic
      bronchoscopy (FOB) on the diagnostic yield of BAL in HIV-positive patients with
      respiratory symptoms. METHOD: We studied 123 consecutive FOBs with BAL in HIV
      positive patients; 101 of these patients (82%) had received previous
      antimicrobial treatment from 1 to 60 days. Diagnostic yield of BAL for
      Pneumocystis carinii, Mycobacterium tuberculosis, and bacterial pneumonia was
      compared between patients with and without previous empiric treatments. RESULTS:
      A diagnosis was obtained in 85 patients (69%), of whom 17 (20%) had multiple
      infections. Diagnostic yield was higher in patients without previous treatment,
      91% (20/22) compared with 64% (65/101), p < 0.03. Diagnostic yield was also
      higher for bacterial pneumonia: seven isolations from 22 patients not receiving
      previous empiric treatment (32%), compared with 11 of those who had (11%; p <
      0.02). The duration of empiric treatment against P carinii in patients in whom it
      was isolated was significantly shorter than in those in whom P carinii was not
      detected (3.5 +/- 1.8 days compared with 5.2 +/- 2.4 days; p = 0.003). FOB
      permitted a change in treatment in 62% of patients with a final diagnosis.
      CONCLUSION: This study demonstrates that empiric treatments prior to FOB
      significantly impair the diagnostic yield of BAL in detecting common pathogens in
      HIV-infected patients with respiratory symptoms.

PMID- 9149568
TI  - Utility of lactate dehydrogenase vs radiographic severity in the differential
      diagnosis of Pneumocystis carinii pneumonia.
AB  - STUDY OBJECTIVES: In patients with HIV infection, serum lactate dehydrogenase
      (LDH) level is commonly stated to be more elevated in Pneumocystis carinii
      pneumonia (PCP) than in non-PCP. We hypothesized that LDH level reflects
      radiographic extent and severity of pneumonia rather than P carinii infection
      specifically and therefore is not useful in the differential diagnosis of lung
      infections in AIDS. DESIGN: We compared radiographic features and LDH values in
      93 sequential patients with HIV infection and a new hospital admission for
      pneumonia (53 PCP and 40 non-PCP) after excluding all patients with other
      potential causes for elevated LDH levels. The chest radiograph was graded using a
      quantitative scale (0 to 24) to assess radiographic extent and severity of
      pneumonia by two independent observers in blinded fashion. The relationship
      between radiographic score and hospital admission LDH level was analyzed by
      linear regression and Bayesian analysis was applied to different LDH ranges to
      calculate the clinical value of LDH measurements. SETTING: Tertiary care teaching
      hospital and regional AIDS referral center. RESULTS: Mean LDH level was higher in
      the PCP group (1.217 +/- 88 U/L compared with 776 +/- 55 U/L; p < 0.001), as was
      mean radiographic score (12.4 +/- 0.6 for PCP compared with 6.3 +/- 0.5 for non
      PCP; p < 0.001). For the whole sample of 93, LDH level was significantly related
      to chest radiographic score (r = 0.43, p < 0.0001). Significant overlap occurred
      between the two groups at all levels of LDH such that no cutoff level could be
      established that impacted significantly on posttest probability of PCP, whereas a
      radiographic score of > 12 yielded a 96% posttest probability of PCP.
      CONCLUSIONS: Serum LDH level reflects the degree of radiographic abnormality and
      is elevated in both PCP and non-PCP pneumonia to an extent that limits its
      utility in differentiating the two processes in hospitalized patients. The extent
      of radiographic involvement more clearly distinguishes the two conditions.

PMID- 9149569
TI  - Alveolar damage in AIDS-related Pneumocystis carinii pneumonia.
AB  - OBJECTIVE: Pneumocystis carinii pneumonia is the most common and serious of the
      pulmonary complications of AIDS. Despite this, many basic aspects in the
      pathogenesis of HIV-associated P carinii pneumonia are unknown. We therefore
      undertook a light and electron microscopic study of transbronchial biopsy
      specimens to compare pathologic features of P carinii pneumonia and other HIV
      related lung diseases. DESIGN AND PATIENTS: Thirty-seven consecutive HIV-infected
      patients undergoing a diagnostic bronchoscopy. RESULTS: P carinii pneumonia was
      characterized by an increase in inflammation, edema, exudate, fibrosts, type II
      pneumocyte proliferation, and cellular infiltration of the alveolar wall when
      compared with other lung diseases (all p < 0.05). Electron microscopy showed
      apposition of the trophozoite to the type I pneumocyte. Erosion of type I
      pneumocytes was observed in 13 of 15 patients with P carinii pneumonia, whereas
      none without P carinii pneumonia had this finding (p < 0.05). Erosion of the type
      II pneumocyte was not observed. CONCLUSION: Inflammation, interstitial fibrosis,
      and alveolar epithelial erosion are characteristic features of P carinii
      pneumonia. The changes may form the pathologic basis for the respiratory failure
      seen in patients with P carinii pneumonia. Electron microscopy did not show any
      diagnostie advantage over conventional light microscopy using routine stains.

PMID- 9149570
TI  - Aerosol delivery during continuous nebulization.
AB  - BACKGROUND AND OBJECTIVES: Continuous administration of aerosolized beta 2
      agonists has been suggested as an effective treatment for severe reversible
      airways disease. To facilitate continuous therapy and avoid a feed system for
      small-volume nebulizers (SVNs), a large-volume medication nebulizer (Vortran
      HEART) was developed. The goal of this study was to determine actual drug
      delivery of the HEART and conventional SVNs for both adult and pediatric
      breathing patterns. DESIGN: Output studies were conducted on comparable samples
      of CIS-US AeroTech II and Hospitak PowerMist SVNs and Vortran HEART large-volume
      continuous nebulizers. To duplicate clinical aerosol delivery via an aerosol
      mask, drug particles were inhaled through the mouth of a model of a human face
      for two test breathing patterns (adult = tidal volume (Vt) of 500 mL, 20
      breaths/min, duty cycle of 40%; pediatric = VT of 100 mL, 35 breaths/min, duty
      cycle of 40%), generated by a ventilator. Radiolabeled particles of saline
      solution, confirmed to behave identically to albuterol, were collected on
      absolute filters at the mouth of the face to measure the actual mass of albuterol
      particles delivered to the airway opening. RESULTS: The AeroTech II and PowerMist
      SVNs delivered 5.14 and 3.74 mg/h, respectively, for the adult breathing pattern
      and 2.97 and 2.48 mg/h, respectively, for the pediatric breathing pattern. Drug
      delivery rates of the HEART were a function of drug concentration and ranged from
      0.87 to 3.48 mg/h for the adult breathing pattern. For the pediatric breathing
      pattern, drug delivery rate was a function of drug concentration and inspired
      minute ventilation and ranged from 0.41 to 1.83 mg/h. CONCLUSION: Our data
      demonstrate that drug delivery to the patient, expressed as inhaled mass over
      time, is similar for continuous nebulization (HEART system) and intermittently
      filled SVNs. In addition, for all nebulizers, the influence of the pediatric
      breathing pattern needs to be considered. Continuous nebulization permits the
      redistribution of health-care personnel and may reduce the costs of therapy.

PMID- 9149571
TI  - The choice of jet nebulizer, nebulizing flow, and addition of albuterol affects
      the output of tobramycin aerosols.
AB  - The use of inhaled antibiotics in the treatment of cystic fibrosis has become
      widespread despite controversy in the literature as to the appropriate dosing
      regimen and its effectiveness. This study compared two tobramycin (T)
      preparations (one with and one without the addition of albuterol) using two
      different jet nebulizers in order to determine if drug output would be affected.
      Using calibrated flows from a dry compressed gas source of 6 and 8 L/min as well
      as a specific compressor (Pulmo-Aide), the Hudson 1720 nebulizer was compared
      with the newer disposable Hudson 1730. The albuterol preparation used in this
      study was the Ventolin (albuterol) Respirator Solution (VRS). The nebulizers were
      charged with (1) 2 mL T (80 mg/2 mL) with 0.5 mL VRS (5 mg/mL) and normal saline
      solution to make the total nebulizer charge of 3 or 4 mL, or (2) 2 mL T and
      either 1 or 2 mL normal saline solution. A laser diffraction analyzer (Malvern
      2600) was used to determine the aerosol particle size distribution. From the
      distribution, the respirable fraction, which is the fraction of aerosol that
      could enter and remain in the lungs, was calculated. For all solutions and each
      particular flow, the Hudson 1730 had a larger respirable fraction of T. The
      addition of VRS lowered the surface tension of the solution in the nebulizer and
      resulted in a greater output of T. This effect was most apparent for the 3-mL
      volume fills of the Hudson 1720. The greatest differences were between the 3-mL
      nebulizer charges of T using the Hudson 1720 driven by a flow of 6 L/min, which
      produced 8 mg of T in the respirable fraction, compared with 35 mg produced by
      the Hudson 1730 driven by a flow of 8 L/min. These results suggest that different
      nebulizers, different nebulizer solutions, and different techniques of
      nebulization may result in very different amounts of T aerosol output in the
      respirable fraction.

PMID- 9149572
TI  - The usefulness of diagnostic tests on pericardial fluid.
AB  - STUDY OBJECTIVES: To determine the physical, chemical, and cellular
      characteristics of pericardial fluid in various disease states and to assess
      their diagnostic accuracies. SETTING: A metropolitan university hospital. DESIGN:
      Consecutive case series. PATIENTS: One hundred seventy-five hospital patients,
      aged 1 month to 87 years, who had undergone pericardiocentesis (n = 165) or
      control subjects who had undergone open heart surgery (n = 10) between 1984 and
      1996. MEASUREMENTS: The appearance of pericardial fluid and results of chemistry
      tests, cell counts, cytologic studies, Gram's stain, and microbial cultures were
      obtained by chart review. The etiology of each pericardial fluid sample was
      determined using prospective diagnostic criteria. RESULTS: Exudates differed from
      transudates by higher leukocyte counts and ratios of fluid to serum lactate
      dehydrogenase levels. Fluid glucose levels were significantly less in exudates.
      Sensitivity for detecting exudates was high for specific gravity > 1.015 (90%),
      fluid total protein > 3.0 g/dL (97%), fluid to serum protein ratio > 0.5 (96%),
      fluid lactate dehydrogenase ratio > 0.6 (94%), and fluid to serum glucose ratio <
      1.0 (85%). None of these indicators were specific. Fluid total protein and
      specific gravity were moderately correlated (r = 0.56). Fluid cytologic study had
      a sensitivity of 92% and specificity of 100% for malignant effusion. No other
      test was diagnostic for a specific etiology. Among infection-associated
      effusions, culture-positive fluid had more neutrophils, higher lactate
      dehydrogenase levels, and lower ratios of fluid to serum glucose than culture
      negative (parainfective) fluid. CONCLUSIONS: Evaluation of pericardial fluid
      might be limited to cell count, glucose, protein, and lactate dehydrogenase
      determinations plus bacterial culture and cytology. While not used routinely,
      other tests that may be highly specific for particular diseases should be ordered
      only to confirm a high clinical suspicion.

PMID- 9149573
TI  - Noninvasive assessment of right ventricular diastolic function by electrical
      impedance tomography.
AB  - STUDY OBJECTIVES: Electrical impedance tomography (EIT) offers the possibility to
      study blood volume changes within the right atrium during the cardiac cycle. The
      aim of this study was to determine the applicability of EIT in the assessment of
      right ventricular diastolic function in COPD. DESIGN: By means of region of
      interest analysis, impedance changes within the right atrium during the cardiac
      cycle were plotted as a function of time. As a diastolic index of the right
      ventricle, the right atrium emptying volume (RAEV), defined as the ratio between
      the volume change during the rapid filling phase relative to the total
      ventricular filling volume, was calculated. In a first study, the validity of the
      EIT method was assessed by comparison of the RAEV measured by EIT and MRI in a
      group of eight patients with severe COPD and seven control subjects. A second
      study was undertaken to assess the relation between RAEV and pulmonary artery
      pressure in a group of 27 patients measured by right-sided heart catheterization.
      RESULTS: The correlation coefficient between RAEV measured with MRI and EIT was
      0.78. The difference between RAEV measured by MRI and EIT was 8.3 +/- 15.7% (mean
      +/- SD) for the control subjects and 3.5 +/- 10.9% for the COPD patients. RAEV
      values measured by EIT and MRI were larger in the control group (47.1 +/- 7.6%)
      compared with the patient group (38.1 +/- 10.4%). There was a clear nonlinear
      relationship between RAEV and the pulmonary artery pressure (y = 315 x-0.64, r =
      0.83, p < 0.001). CONCLUSION: Our results indicate that RAEV measured by EIT is a
      useful noninvasive and inexpensive method for assessing right ventricular
      diastolic function in COPD patients.

PMID- 9149574
TI  - Intraoperative transesophageal echocardiographic assessment of vascular
      anastomoses in lung transplantation. A report on 18 cases.
AB  - BACKGROUND: In patients after lung transplantation, dysfunction of pulmonary
      venous and artery anastomoses leading to reoperation is described. METHODS AND
      RESULTS: Pulmonary artery and vein anastomoses were evaluated intraoperatively by
      monoplane transesophageal echocardiography (TEE) in 18 patients undergoing lung
      transplantation (nine right, five left single lung transplantations, and four
      bilateral transplantations). All 13 right pulmonary artery anastomoses and all 22
      pulmonary vein anastomoses could be visualized by TEE. None of the nine left
      pulmonary anastomoses could be visualized. Of the 13 right pulmonary anastomoses,
      12 were considered normal, their diameter ranging from 1 to 1.7 cm (mean, 1.26 +/
      0.24 cm). A moderate stenosis of one pulmonary artery anastomosis was identified
      but did not require reoperation. Of the 22 pulmonary vein anastomoses, 16 were
      considered normal, their diameter being > 0.5 cm and the peak systolic flow
      velocity < or = 1 m/s at the location of the anastomoses. In five cases, the
      anastomoses were not considered normal, but reoperation was not indicated. In one
      case, a severe stenosis of pulmonary vein associated with graft dysfunction led
      to an early reoperation. CONCLUSION: Intraoperative TEE during lung
      transplantation contributes to the immediate evaluation of pulmonary vein and
      right pulmonary artery anastomoses and allows immediate surgical correction.
      Further investigations are necessary to establish threshold values requiring
      reoperation.

PMID- 9149575
TI  - Comparison of transesophageal and transthoracic contrast echocardiography for
      detection of an intrapulmonary shunt in liver disease.
AB  - STUDY OBJECTIVES: Contrast transthoracic echocardiography (TTE) is currently used
      to identify intrapulmonary shunt (IPS) in patients with end-stage liver disease.
      The aim of this study was to compare the use of contrast TTE and transesophageal
      echocardiography (TEE) in detecting IPS. DESIGN: Thirty-seven consecutive
      outpatients with severe liver disease awaiting liver transplantation underwent
      contrast TEE and TTE. The IPS was assessed semiquantitatively in four grades with
      TEE and as positive or negative with TTE. SETTING: ICU. INTERVENTIONS: Patients
      underwent contrast TEE after pharyngeal anesthesia alone followed by contrast
      TTE. Contrast echocardiography was performed with a modified fluid gelatin
      solution. RESULTS: Overall detection rate of an IPS was 51% with TEE and 32% with
      TTE (p < 0.001). Four patients had an IPS detected with TEE but not with TTE.
      Quality of imaging was poor in 22% with TTE and 0% with TEE (p < 0.001). A PaO2 <
      80 mm Hg or a dyspnea was associated with an IPS in 56% and 50% of patients with
      TEE and in 33% and 25% with TTE, respectively. CONCLUSION: Contrast-enhanced TEE
      is superior to TTE for detecting an IPS in patients with severe liver disease
      awaiting liver transplantation. The use of gelatin contrast solution allows an
      early detection of IPS. Because of the high sensitivity of TEE, all patients
      suspected of hepatopulmonary syndrome should undergo TEE in search of an IPS if
      TTE is normal.

PMID- 9149576
TI  - Thrombolytic therapy for pulmonary embolism. Frequency of intracranial hemorrhage
      and associated risk factors.
AB  - STUDY OBJECTIVES: To determine the risk factors and frequency of intracranial
      hemorrhage among patients undergoing thrombolysis for pulmonary embolism. DESIGN:
      A retrospective descriptive and controlled analysis. SETTING: Hospitalized
      patients at centers in the United States, Canada, and Italy. PATIENTS: All had
      evidence of pulmonary embolism on perfusion scans or angiography. INTERVENTIONS:
      None. MEASUREMENTS AND RESULTS: Data were analyzed on 312 patients from five
      previously reported studies of pulmonary embolism thrombolysis. The frequency of
      intracranial hemorrhage up to 14 days after pulmonary embolism thrombolysis was 6
      of 312 or 1.9% (95% confidence interval, 0.7 to 4.1%). Two of six intracranial
      hemorrhages were fatal. Two of the six patients received thrombolysis in
      violation of the protocol because they had pre-existing, known intracranial
      disease. Average diastolic BP at the time of hospital admission was significantly
      elevated in patients who developed an intracranial hemorrhage (90.3 +/- 15.1 mm
      Hg) compared with those who did not (77.6 +/- 10.9 mm Hg; p = 0.04). Other
      baseline characteristics and laboratory data were similar in both groups.
      Decreased level of consciousness, hemiparesis, and visual field deficits were the
      most common clinical signs of intracranial hemorrhage. CONCLUSIONS: Intracranial
      hemorrhage after pulmonary embolism thrombolysis is an infrequent but often grave
      complication. Meticulous patient screening before administering thrombolysis is
      imperative. Diastolic hypertension at the time of hospital admission is a risk
      factor for intracranial hemorrhage after pulmonary embolism thrombolysis.

PMID- 9149577
TI  - Prevalence of acute pulmonary embolism in central and subsegmental pulmonary
      arteries and relation to probability interpretation of ventilation/perfusion lung
      scans.
AB  - PURPOSE: The purpose of this investigation is to determine the prevalence of
      acute pulmonary embolism (PE) limited to subsegmental pulmonary arteries.
      BACKGROUND: Contrast-enhanced helical (spiral) and electron-beam CT, in the hands
      of experienced radiologists who are skillful with this modality, are sensitive
      for the detection of acute PE in central pulmonary arteries, but have a low
      sensitivity for the detection of PE limited to subsegmental pulmonary arteries.
      The potential for CT to diagnose PE, therefore, is partially dependent on the
      prevalence of PE limited to subsegmental pulmonary arteries. METHODS: Data are
      from the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). The
      largest pulmonary arteries that showed PE, as interpreted by the PIOPED
      angiographic readers, were identified in 375 patients in PIOPED with
      angiographically diagnosed PE. RESULTS: Among all patients with PE, 6% (95%
      confidence interval [CI], 4 to 9%) had PE limited to subsegmental branches of the
      pulmonary artery. Patients with high-probability ventilation/ perfusion (V/Q)
      scans had PE limited to subsegmental branches in only 1% (95% CI, 0 to 4%). Among
      patients with low-probability V/Q lung scans, 17% (95% CI, 8 to 29%) had PE
      limited to the subsegmental branches. Patients with low-probability V/Q scans and
      no prior cardiopulmonary disease had PE limited to the subsegmental pulmonary
      arteries in 30% (95% CI, 13 to 53%), whereas patients with low-probability V/Q
      scans who had prior cardiopulmonary disease had PE limited to subsegmental
      pulmonary arteries in 8% (95% CI, 2 to 22%) (p < 0.05). CONCLUSION: Based on data
      from all patients with PE in PIOPED, the prevalence of PE limited to subsegmental
      pulmonary arteries is low, 6%. PE limited to subsegmental pulmonary arteries was
      most prevalent among patients with low-probability V/Q scans, particularly if
      they had no prior cardiopulmonary disease.

PMID- 9149578
TI  - The effect of salmeterol on nocturnal symptoms, airway function, and inflammation
      in asthma.
AB  - STUDY OBJECTIVE: To determine the efficacy of salmeterol alone in a group of
      patients with moderate asthma with nocturnal worsening of symptoms. DESIGN:
      Double-blind, randomized, placebo-controlled crossover study. SETTING: Tertiary
      care hospital specializing in respiratory diseases. PARTICIPANTS: Ten patients
      with nocturnal asthma. INTERVENTIONS: Subjects were randomized to salmeterol, 100
      micrograms twice daily, or placebo for 6 weeks with a 1-week washout between
      treatment periods. Symptoms, nocturnal awakenings, and beta 2-agonist use were
      recorded daily. Spirometry was performed at weeks 1 and 6 of each period at
      bedtime and at 4 AM, and methacholine challenge was performed at 4 AM followed by
      bronchoscopy with BAL. BAL fluid analysis included cell count and differential
      count, eosinophil cationic protein, Charcot-Leyden crystal protein, leukotriene
      B4, and thromboxane B2. RESULTS: The percentage of nights with awakenings
      decreased significantly with salmeterol (69.8 +/- 8.7% vs 30.6 +/- 10.8% for
      placebo and salmeterol, respectively; p = 0.02). The percentage of 24-h days with
      supplemental inhaled beta 2-agonist use significantly decreased with salmeterol
      (85.9 +/- 9.4% vs 70.4 +/- 10.1% for placebo and salmeterol, respectively; p =
      0.04). There were no significant differences in bronchial reactivity, 4 AM FEV1,
      overnight percentage change in FEV1, or indexes of airway inflammation.
      CONCLUSIONS: Salmeterol alone improves the number of nocturnal awakenings and
      supplemental 24-h beta 2-agonist use in nocturnal asthma without significantly
      altering lung function and airway inflammation.

PMID- 9149579
TI  - Lung epithelial permeability and bronchial responsiveness in subjects with stable
      asthma.
AB  - Lung epithelial permeability of asthmatic patients has been reported to be
      similar or lower than that of healthy subjects and to be correlated or not to
      bronchial hyperresponsiveness. To clarify these discrepancies, we evaluated 99mTc
      DTPA pulmonary clearance in a group of carefully selected asthmatic patients with
      mild, stable asthma (n = 13; seven women; mean age +/- SD = 27.69 +/- 6.63
      years), and compared them with a group of healthy, nonsmoking subjects (n = 8;
      six women; mean age +/- SD = 24.38 +/- 5.15 years). Selection criteria for
      asthmatics were as follows: baseline FEV1 > or = 80% of predicted values, no
      bronchial infections, and/or no asthma attacks during 4 weeks prior to study and
      peak expiratory flow rate variability lower than 20%, over a period of 3 weeks.
      Patients controlled symptoms with beta 2-adrenergic drugs only, regularly or on
      demand. Mean baseline FEV1 (+/-SD) as percent of predicted was 102.38 +/- 13.97
      and 112.88 +/- 18.36, respectively (p < 0.05). In the asthmatic group, bronchial
      responsiveness to methacholine (PC20 M FEV1) ranged between 0.55 and 28.5 mg/mL.
      Mean value (+/-SD) of DTPA clearance from lungs to blood (evaluated on the first
      10 min out of 30 min of the curves) in the asthmatic group was not different from
      that of control group (68.31 +/- 21.46 and 69.5 +/- 15.73). In the asthmatic
      patients, there was no correlation between PC20 M values and DTPA T1/2 min of the
      whole lung, nor between PC20 M and inner and outer lung clearance zones.
      Moreover, both in asthmatics and healthy subjects, DTPA clearance of outer
      (alveolar) zones was significantly faster than that of inner (bronchial) zones
      (57.69 +/- 19.94 vs 102.08 +/- 38.19, p < 0.001, and 59.75 +/- 12.49 vs 103.5 +/-
      31.86, p < 0.003, respectively). Our data show that DTPA clearance in patients
      with stable asthma is similar to that found in healthy subjects; it is not
      correlated to degree of bronchial responsiveness and occurs more rapidly in the
      outer zones than in the inner zones, both in asthmatic patients and in healthy
      subjects. Thus, to date, DTPA clearance index is not a valid tool for identifying
      and/or monitoring asthmatic patients.

PMID- 9149581
TI  - Quantitative aspiration during sleep in normal subjects.
AB  - STUDY OBJECTIVE: To determine the within-subject variability and to estimate the
      quantity of occult aspiration of nasopharyngeal secretions during sleep in normal
      humans. DESIGN: Prospective duplicate full-night sleep studies. SETTING:
      Pulmonary sleep laboratory, university hospital. PARTICIPANTS: Ten normal male
      volunteers aged 22 to 55 years. INTERVENTIONS: Two full-night polysomnographic
      recordings with infusion of 2 mL/h radioactive 99mTc tracer into the nasopharynx
      through a small catheter during EEG-documented sleep. Standard lung scans were
      conducted immediately following final awakening. Aspiration was defined as the
      presence of radioactivity in the pulmonary parenchyma on two separate views.
      RESULTS: A mean sleep efficiency of 85.7 +/- 2.6% was found with no difference
      between the two study nights. A total of 5 of the 10 subjects studied had tracer
      evident in the pulmonary parenchyma following final awakening. Three had the
      tracer apparent following the first-night study and four had tracer apparent
      following the second-night study. Thus, two subjects aspirated on both nights.
      Comparing the subjects who aspirated with those who did not, no significant
      difference could be found for age, time spent in bed, sleep efficiency, apnea
      hypopnea index, arousal plus awakening index, or percent of sleep time spent in a
      supine position. The quantities of tracer aspirated were on the order of
      magnitude of 0.01 to 0.2 mL. CONCLUSIONS: Aspiration measured by this technique
      occurs commonly in healthy young men during sleep, is unrelated to sleep quality,
      and is variable within subjects studied on more than one occasion. The quantity
      aspirated is of an order of magnitude likely to contain bacterial organisms in
      physiologically significant quantities.

PMID- 9149580
TI  - Bed partners' assessment of nasal continuous positive airway pressure therapy in
      obstructive sleep apnea.
AB  - STUDY OBJECTIVE: This study aimed to evaluate the effects of nasal continuous
      positive airway pressure (nCPAP) therapy on sleep and daytime symptoms of bed
      partners and patients with obstructive sleep apnea (OSA). DESIGN: A cross
      sectional questionnaire survey. SETTING: The sleep laboratory of a university
      teaching hospital. PATIENTS: Ninety-one consecutive OSA patients within 2 to 12
      months of being prescribed nCPAP. RESULTS: Eighty-five replies (93% of sample
      population) were received. Twelve patients (14% of replies) had discontinued
      nCPAP therapy; two patients had not yet been supplied with an nCPAP device.
      Seventy-one patients continued nightly nCPAP therapy. Bed partners of these
      patients (n = 55) answered a separate questionnaire assessing improvements in
      their own sleep quality, daytime alertness, mood and quality of life (questions 1
      to 4), and evaluated the same parameters for the patients (questions 5 to 8).
      Possible scores ranged from -1 (worse) to +3 (marked improvement). Questions 1 to
      4 yielded median scores of 2, 1, 1, and 2, respectively, and scores of 3, 3, 2,
      and 3 for questions 5 to 8. A ninth question addressing perceived changes in the
      quality of their relationship resulted in a median score of 2. Mean (SD) Epworth
      sleepiness scores improved from 14.3 (5.8) to 5.2 (4.3) in patients receiving
      therapy (p < 0.005). CONCLUSIONS: These data indicate that bed partners of OSA
      patients treated with nCPAP experience important improvements in symptoms and
      personal relationships. The findings are of practical clinical use when
      counseling patients with OSA and their partners on the likely impact of nCPAP
      therapy on their quality of life.

PMID- 9149582
TI  - Group education sessions and compliance with nasal CPAP therapy.
AB  - STUDY OBJECTIVES: To determine an effective means of improving compliance with
      nasal continuous positive airway pressure (CPAP) for obstructive sleep apnea
      (OSA). DESIGN: Retrospective chart review. SETTING: An outpatient clinic at a
      Veterans Affairs Medical Center. PATIENTS: Seventy-three patients with OSA.
      INTERVENTIONS: Hour meters on CPAP machines provided documentation of nightly
      machine use. A 2-h group CPAP clinic, scheduled every 6 months, provided
      education, support, symptom treatment, and equipment monitoring for all CPAP
      patients. RESULTS: Twenty-five patients had hour meter readings taken at their
      first CPAP clinic. In these patients, nightly CPAP use increased from 5.2 +/- 0.6
      to 6.3 +/- 0.6 h per night after attendance at one CPAP clinic (p < 0.05). CPAP
      use increased from 5.2 +/- 0.5 before CPAP clinic to 6.3 +/- 0.6 h per night
      after attendance at all subsequent CPAP clinics for 34 patients (p < 0.05), an
      improvement that was sustained over 605 +/- 34 days. Twenty-nine percent of
      patients increased nightly CPAP use by at least 2 h, while only 6% decreased by >
      or = 2 h (p < 0.025). Patients receiving supplemental oxygen had higher CPAP use
      prior to CPAP clinic compared to patients not receiving oxygen (p < 0.05).
      CONCLUSIONS: Attendance in a group clinic designed to encourage patient
      compliance with CPAP therapy provided a simple and effective means of improving
      treatment of OSA.

PMID- 9149583
TI  - Postpneumonectomy pulmonary edema. A retrospective analysis of incidence and
      possible risk factors.
AB  - OBJECTIVE: To analyze the incidence of postpneumonectomy pulmonary edema (PPE)
      and to determine potential risk factors for PPE. MATERIAL AND METHODS: A group of
      197 patients was studied retrospectively, and the incidence of PPE was recorded
      over a 5-year period. Preoperative, perioperative, and postoperative clinical
      data were collected, and preoperative and postoperative chest radiographs were
      reviewed. A scoring system was used to distinguish between premanifest and
      manifest PPE. Postpneumonectomy patients with pulmonary edema, with no clinically
      evident cause, were considered to have PPE. RESULTS: The incidence of premanifest
      PPE was 12.2% (n = 24), and that of manifest PPE was 2.5% (n = 5). Mortality in
      the group of patients who developed manifest PPE was 100%. Two significant
      perioperative associations were found in the PPE group. One was the
      administration of fresh frozen plasma (FFP) transfusions (relative risk, 4.3; 95%
      confidence interval, 1.3 to 14.4 corrected for age and sex), while the other was
      higher mechanical ventilation pressures during surgery (relative risk, 3.0; 95%
      confidence interval, 1.2 to 7.3). CONCLUSION: Our data suggest that FFP
      transfusions form an important risk factor for PPE. The mechanism may be an
      increased permeability of the pulmonary vessels due to an immunologic reaction
      after multiple FFP transfusions. The significantly higher mechanical ventilation
      pressures we found in the PPE group may be explained as an early sign of the
      development of PPE.

PMID- 9149584
TI  - Complete lobar collapse following pulmonary lobectomy. Its incidence,
      predisposing factors, and clinical ramifications.
AB  - STUDY OBJECTIVE: To define the most severe form of postlobectomy atelectasis and
      determine its incidence, predisposing factors, and clinical ramifications.
      DESIGN: Retrospective case control. SETTING: The thoracic surgery unit at a 900
      bed tertiary care hospital. PATIENTS OR PARTICIPANTS: Two hundred eighteen
      patients undergoing pulmonary lobectomy or bilobectomy over a 7-year time period.
      MEASUREMENTS AND RESULTS: Severe postlobectomy atelectasis (SPLA) was defined as
      complete ipsilateral lobar or bilobar collapse with whiteout of the involved
      lobe(s) and mediastinal shift on the chest radiograph. Data were collected
      consisting of patient age, lobe(s) resected, type of postoperative pain control,
      length of hospital and ICU stay, preoperative pulmonary function, and single- vs
      double-lumen tube intubation during surgery. The incidence of SPLA was 7.8%,
      comprising 24.6% of all postoperative complications seen. There was no
      statistically significant difference in patient age, preoperative room air PO2,
      and preoperative FEV1/FVC ratio for the SPLA group vs the group without this
      complication. Patients with SPLA had significantly longer ICU stays (112.7 h vs
      28.4 h; p < 0.001) and hospital stays (14.7 days vs 9.3 days; p < 0.001) than the
      patients without complications. Patients undergoing right upper lobectomy, both
      alone or in combination with the right middle lobe, had a significantly higher
      incidence of SPLA when compared with all other types of resections (15.5% vs
      3.0%; p < 0.005). There was no influence on the incidence of SPLA when the types
      of postoperative pain control regimen and endotracheal tubes used were examined.
      CONCLUSIONS: We conclude that SPLA as defined in this study is an important
      postoperative complication with a significant incidence. Although patients
      undergoing right upper lobectomy are markedly predisposed to this problem, the
      exact pathophysiology remains unclear. Factors shown to be causes of less severe
      forms of postoperative atelectasis do not seem to contribute to the formation of
      SPLA, indicating that these two complications may be two unrelated entities.

PMID- 9149585
TI  - Is atelectasis following aortocoronary bypass related to temperature?
AB  - OBJECTIVE: To determine the frequency of acute postoperative atelectasis in
      patients undergoing aortocoronary bypass with either normothermic (warm) or
      hypothermic (cold) technique. DESIGN: Prospective, randomized study comparing two
      groups. SETTING: University-affiliated hospital. PATIENTS: Three hundred thirty
      one patients (166 cold and 165 warm) undergoing isolated aortocoronary bypass.
      MEASUREMENTS: Chest radiographs were obtained preoperatively, on the day of
      surgery, and subsequently as clinically indicated until discharge from the
      hospital. Radiologist (blinded to the patient allocation into warm or cold group)
      scored the atelectasis from 0 to 3 based on its severity. Regression analysis was
      used to determine if there was any difference in the atelectasis scores between
      the two groups. RESULTS: Mean daily postoperative atelectasis scores were not
      different between the cold and warm groups. The number of patients requiring
      chest radiographs was similar in both groups. The percent of patients with
      abnormal chest radiographs was similar in both groups. CONCLUSION: The
      temperature of cardioplegia has no effect on the development of atelectasis
      following aortocoronary bypass, and therefore temperature-related cold injury is
      not a major cause of atelectasis following this type of surgery.

PMID- 9149586
TI  - Noninvasive measurement of cardiac output by an acetylene uptake technique and
      simultaneous comparison with thermodilution in ICU patients.
AB  - A simple, accurate, and noninvasive method of cardiac output measurement can be
      an extremely useful tool for the clinician and researcher. This study used the
      acetylene gas uptake technique to measure the absorption of acetylene into the
      pulmonary circulation during a constant exhalation, which is proportional to the
      pulmonary capillary blood flow and to the cardiac output, assuming no anatomic
      shunts. We compared cardiac output measured simultaneously by this and by the
      standard thermodilution (TD) technique in 21 patients in the ICU with a variety
      of medical and surgical conditions and a wide range of cardiac outputs. We also
      compared the two techniques in 19 ambulatory patients with a 2-h interval between
      the invasive and noninvasive test to assess variability over time. The two tests
      had an excellent correlation when done simultaneously with a correlation
      coefficient of 0.89 (p < 0.001). With a 2-h interval between the two tests, the
      correlation coefficient was 0.66 (p = 0.0018). Nine patients in the simultaneous
      group had cardiomyopathy. When they were excluded, the correlation coefficient
      increased to 0.96. Most of these patients had documented tricuspid regurgitation
      (TR), which may underlie the greater difference between acetylene uptake and TD
      values, with consistently higher TD values in these patients. This study confirms
      the correlation between the acetylene uptake and the standard invasive TD
      techniques in sick patients with various medical and surgical conditions and a
      wide range of cardiac outputs. Furthermore, we believe this would be a more
      accurate method for measuring cardiac output in patients with cardiomyopathy and
      TR because it is based only on pulmonary capillary blood flow.

PMID- 9149587
TI  - Release of lactate by the lung in acute lung injury.
AB  - The pathogenesis of hyperlactatemia during sepsis is poorly understood. We have
      previously described an increase in lactate concentration across the lung in the
      dog during early endotoxemia. Accordingly, we sought to determine if the lung
      releases lactate in humans and what relation this has with lung injury. METHODS:
      We measured lactate concentrations across the lung and lung injury scores (LIS)
      in two groups of patients. Group 1 consisted of nine patients with acute lung
      injury (LIS > or = 2.0) and elevated lactate concentrations (> 2.0 mmol/L). Group
      2 contained 12 patients with no acute lung injury (LIS scores < or = 1.5), with
      or without increased lactate concentrations. Simultaneous measurements of plasma
      lactate and blood gases were obtained from indwelling arterial and pulmonary
      artery catheters. Measurements of cardiac output were also obtained. Lactate
      measurements were done using a lactate analyzer (YSI; Yellow Springs, Ohio).
      RESULTS: For each patient with acute lung injury and hyperlactatemia, an arterial
      venous lactate gradient existed demonstrating release of lactate by the lung.
      This gradient persisted after correction for changes in hemoconcentration across
      the lung. The lactate gradient across the lung was 0.4 +/- 0.2 mmol/L for group 1
      vs 0.05 +/- 0.1 mmol/L for group 2 (p = 0.001). This corresponded to a mean
      pulmonary lactate flux of 231.3 +/- 211.3 vs 5.0 +/- 37.2 mmol/h (p = 0.001). The
      lactate flux and the arterial-venous lactate difference correlated with LIS both
      for the entire sample and for the subgroup with hyperlactatemia (r = 0.69, p <
      0.01). Pulmonary lactate flux was not related to arterial lactate levels (r =
      0.25). CONCLUSION: In patients with acute lung injury and hyperlactatemia, the
      lung is a major source of lactate and lactate flux correlates with LIS. This
      lactate flux could explain some of the hyperlactatemia seen in sepsis.

PMID- 9149589
TI  - Comparison of pressure support ventilation and assist-control ventilation in the
      treatment of respiratory failure.
AB  - STUDY OBJECTIVE: To assess whether pressure support ventilation (PSV) could be
      used as an alternative ventilatory mode to assist-control (A/C) ventilation in
      the treatment of respiratory failure. DESIGN: A short-term (4-h) prospective
      study in which the beneficial effect of PSV on respiratory mechanics, gas
      exchange, arterial oxygenation, cardiovascular hemodynamics, and oxygen
      consumption was compared with A/C ventilation. SETTING: ICU of a community
      hospital. PATIENTS: Forty-five patients (mean age, 62.8 [11.8] years) with
      respiratory failure secondary to COPD, restrictive disorders, or neuromuscular
      disease requiring mechanical ventilatory support in the ICU were selected for
      study. INTERVENTIONS: The mean duration of mechanical ventilation before the
      study was 7.16 (8.64) days. Patients were switched to the PSV mode of the
      mechanical ventilator for a period of 4 h after which conventional A/C
      ventilation was resumed. RESULTS: Patients supported with PSV compared with A/C
      ventilation showed significantly higher tidal volume, minute ventilation, and
      inspiratory time in association with significantly lower pressure in the airway
      and I:E ratio. With regard to gas exchange data, an increase in dead space/tidal
      volume ratio (VD/VT), decrease in PaO2, and statistically but not clinically
      significant alteration of arterial oxygenation indexes were noted. However, when
      patients with COPD, restrictive disorders, and neuromuscular disease were
      compared, significant changes in arterial oxygenation parameters were found only
      in patients with restrictive disorders. There were significant decreases in heart
      rate, systolic pulmonary artery pressure, and pulmonary capillary wedge pressure
      when PSV was applied. Oxygen transport and oxygen consumption were unchanged.
      CONCLUSIONS: PSV could be a possible alternative to A/C ventilation in patients
      with respiratory failure. PSV caused an increase in VD/VT in association with a
      significantly lower pressure in the airway and I:E ratio. Randomized studies are
      needed to define the long-term benefits of both respiratory modes and the
      conditions in which PSV may be a valuable alternative to A/C ventilation.

PMID- 9149588
TI  - Infections and the inflammatory response in acute respiratory distress syndrome.
AB  - STUDY OBJECTIVE: Systemic inflammatory response syndrome (SIRS) and infections
      are frequently associated with the development and progression of acute
      respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome
      (MODS). We investigated, at onset and during the progression of ARDS, the
      relationships among (1) clinical variables and biological markers of SIRS, (2)
      infections defined by strict criteria, and (3) patient outcome. Biological
      markers of SIRS included serial measurements of inflammatory cytokines (IC)-tumor
      necrosis factor-alpha (TNF-alpha) and interleukins (IL) 1 beta, 2, 4, 6, and 8-in
      plasma and BAL fluid. METHODS: We prospectively studied two groups of ARDS
      patients: 34 patients treated conventionally (group 1) and nine patients who
      received glucocorticoid rescue treatment for unresolving ARDS (group 2).
      Individual SIRS criteria and SIRS composite score were recorded daily for all
      patients. Plasma IC levels were measured by enzyme-linked immunosorbent assay on
      days 1, 2, 3, 5, 7, 10, and 12 of ARDS and every third day thereafter while
      patients received mechanical ventilation. Unless contraindicated, bilateral BAL
      was performed on day 1, weekly, and when ventilator-associated pneumonia was
      suspected. Patients were closely monitored for the development of nosocomial
      infections (NIs). RESULTS: ICU mortality was similar among patients with and
      without sepsis on admission (54% vs 40%; p < 0.45). Among patients with sepsis
      induced ARDS, mortality was higher in those who subsequently developed NIs (71%
      vs 18%; p < 0.05). At the onset of ARDS, plasma TNF-alpha, IL-1 beta, IL-6, and
      IL-8 levels were significantly higher (p < 0.0001) in nonsurvivors (NS) and in
      those with sepsis (p < 0.0001). The NS group, contrary to survivors (S), had
      persistently elevated plasma IC levels over time. In 17 patients, 36 definitive
      NIs (17 in group 1 and 19 in group 2) were diagnosed by strict criteria. No
      definitive or presumed NIs caused an increase in plasma IC levels above patients'
      preinfection baseline. Daily SIRS components and SIRS composite scores were
      similar among S and NS and among patients with and without sepsis-induced ARDS,
      were unaffected by the development of NI, and did not correlate with plasma IC
      levels. CONCLUSIONS: Sepsis as a precipitating cause of ARDS was associated with
      higher plasma IC levels. However, NIs were not associated with an increase in
      SIRS composite scores, individual SIRS criteria, or plasma IC levels above
      patients' preinfection baseline. SIRS composite scores over time were similar in
      S and NS. SIRS criteria, including fever, were found to be nonspecific for NI.
      Irrespective of etiology of ARDS, plasma IC levels, but not clinical criteria,
      correlated with patient outcome. These findings suggest that final outcome in
      patients with ARDS is related to the magnitude and duration of the host
      inflammatory response and is independent of the precipitating cause of ARDS or
      the development of intercurrent NIs.

PMID- 9149590
TI  - Evidence for a hydrostatic mechanism in human neurogenic pulmonary edema.
AB  - STUDY OBJECTIVES: To identify the relative contribution of hydrostatic and
      permeability mechanisms to the development of human neurogenic pulmonary edema.
      DESIGN: Retrospective review of patients with neurogenic pulmonary edema who had
      pulmonary edema fluid analysis. SETTING: University hospital ICU. PATIENTS:
      Twelve patients with neurogenic pulmonary edema in whom the associated neurologic
      condition was subarachnoid hemorrhage (n = 8, 67%), postcraniotomy (n = 2), and
      stroke (n = 2). MEASUREMENTS: Protein concentration was measured from pulmonary
      edema fluid and plasma samples obtained shortly after the onset of clinical
      pulmonary edema. RESULTS: The mechanism of pulmonary edema was classified
      according to the initial alveolar edema fluid to plasma protein concentration
      ratio. A hydrostatic mechanism (ratio < or = 0.65) was observed in seven
      patients, none of whom had cardiac failure or intravascular volume overload. Five
      patients had evidence for increased permeability (ratio > 0.70). Patients with a
      hydrostatic mechanism had better initial oxygenation (mean +/- SD PaO2/FIO2
      [fraction of inspired oxygen] = 233 +/- 132) compared with patients with
      increased permeability (PaO2/FIo2 = 80 +/- 42), and oxygenation improved more
      rapidly in the hydrostatic patients. Overall mortality (58%) was high, but it was
      related to unresolved neurologic deficits, not to respiratory failure.
      CONCLUSION: Many of our patients had a hydrostatic mechanism for neurogenic
      pulmonary edema. This is a novel observation in humans since prior clinical case
      reports have emphasized increased permeability as the usual mechanism for
      neurogenic pulmonary edema. These findings are consistent with pulmonary
      venoconstriction or transient elevation in left-sided cardiovascular pressures as
      contributing causes to the development of human neurogenic pulmonary edema.

PMID- 9149591
TI  - Increased mortality of older patients with acute respiratory distress syndrome.
AB  - OBJECTIVE: To examine the relationship between age and mortality in ARDS patients
      and evaluate the importance of factors that increase the mortality of older ARDS
      patients. DESIGN: Prospective inception cohort study. SETTING: Community-based
      referral hospital. PATIENTS: Two hundred fifty-six ARDS patients identified from
      May 1987 to December 1990. ARDS was defined by the following: (1) PaO2/PAO2 < or
      = 0.2; (2) pulmonary capillary wedge pressure < or = 15 mm Hg; (3) total static
      thoracic compliance < or = 50 mL/cm H2O; (4) bilateral infiltrates on chest
      radiograph; and (5) an appropriate clinical setting for ARDS. MAIN OUTCOME
      MEASURES: Comparison of organ failure, incidence of sepsis, patient demographics,
      arterial oxygenation, and level of support in those 55 years and younger and
      those older than 55 years of age. Withdrawal of support in patients who died.
      RESULTS: Seventy-two of 112 patients older than 55 years (64%) died vs 65 of 144
      patients 55 years and younger (45%) (p = 0.002). Examination of patient groups
      using age identified older than 55 years as a "cutpoint" above which mortality
      was greater (p = 0.002). Older nonsurvivors did not differ from nonsurvivors 55
      years or younger with respect to gender, smoking history, ARDS risk factors, ARDS
      identifying characteristics, APACHE II (acute physiology and chronic health
      evaluation), number of organ failures, or the incidence of sepsis. In the 48 h
      prior to death, nonsurvivors 55 years and younger had more organ failure (3.4 +/-
      0.2 vs 2.8 +/- 0.2; p = 0.03), higher fraction of inspired oxygen (0.82 +/- 0.03
      vs 0.68 +/- 0.03; p = 0.008), and higher positive end-expiratory pressure levels
      (13 +/- 1 vs 8 +/- 1; p = 0.001) than older nonsurvivors. Despite more severe
      expression of disease, only 32 (50%) nonsurvivors 55 years and younger had
      support withdrawn. Significantly more nonsurvivors older than 55 years (73%) had
      support withdrawn (p = 0.009). Even in the absence of chronic disease states,
      withdrawal was more likely for patients older than 55 years (21/51) than in those
      55 years and younger (3/32; p < 0.001). CONCLUSIONS: Mortality is significantly
      higher for patients with ARDS older than 55 years. Decisions to withdraw support
      are made more often in ARDS patients older than 55 years. These data suggest that
      age bias may influence decisions to withdraw support.

PMID- 9149592
TI  - Clinically recognized cardiac dysfunction: an independent determinant of
      mortality among critically ill patients. Is there a role for serial measurement
      of cardiac troponin I?
AB  - OBJECTIVE: To determine the relative importance of clinically recognized cardiac
      dysfunction and unrecognized cardiac injury to hospital mortality. DESIGN:
      Prospective, blinded, single-center study. SETTING: Medical ICU of Barnes-Jewish
      Hospital, St. Louis, a university-affiliated teaching hospital. PATIENTS: Two
      hundred sixty adult patients requiring admission to the medical ICU.
      INTERVENTIONS: Daily blood collection. MAIN OUTCOME MEASURES: The presence of
      cardiac dysfunction (myocardial infarction, unstable angina, cardiac arrest, or
      congestive heart failure) as determined by the physicians responsible for the
      care of the patient. Daily measurement of levels of cardiac troponin I, a
      sensitive, highly specific, and long-lived marker of myocardial injury. RESULTS:
      Fifty-five (21.2%) patients had clinical evidence of cardiac dysfunction, among
      whom 22 (40%) had an elevated level of cardiac troponin I. A total of 41 (15.8%)
      patients had evidence of acute myocardial injury based on elevated levels of
      cardiac troponin I. Patients with clinically recognized cardiac dysfunction had a
      significantly greater hospital mortality rate compared to patients without
      clinically recognized cardiac dysfunction (45.5% vs 10.2%; p < 0.001). Similarly,
      patients with elevated blood levels of cardiac troponin I had a greater hospital
      mortality rate compared to patients without elevated blood levels of cardiac
      troponin I (26.8% vs 16.0%; p = 0.095). Multiple logistic-regression analysis
      controlling for potential confounding variables demonstrated that the presence of
      clinically recognized cardiac dysfunction was independently associated with
      hospital mortality (adjusted odds ratio = 3.0; 95% confidence interval = 1.9 to
      4.8; p = 0.016). However, having an elevated blood level of cardiac troponin I
      was not found to be an independent determinant of hospital mortality. CONCLUSION:
      Among critically ill medical patients, clinically recognized cardiac dysfunction
      is an independent determinant of hospital mortality. The identification of
      unrecognized cardiac injury, using serial measurements of cardiac troponin I, did
      not independently contribute to the prediction of hospital mortality.

PMID- 9149593
TI  - Radiofrequency volumetric reduction of the tongue. A porcine pilot study for the
      treatment of obstructive sleep apnea syndrome.
AB  - STUDY OBJECTIVE: To investigate, in an animal model, the feasibility of
      radiofrequency (RF) volumetric tongue reduction for the future purpose of
      determining its clinical applications in obstructive sleep apnea syndrome (OSAS).
      DESIGN: The study was performed in three stages, one in vitro bovine stage and
      two in vivo porcine stages. The last stage was a prospective investigation with
      histologic and volumetric analyses to establish outcomes. SETTING: Laboratory and
      operating room of veterinary research center. PARTICIPANTS: A homogeneous
      population of porcine animal models, including seven in stage 2 and 12 in stage
      3. INTERVENTION: RF energy was delivered by a custom-fabricated needle electrode
      and RF generator to the tongue tissue of both the in vitro and in vivo models.
      MEASUREMENTS AND RESULTS: Microultransonic crystals were used to measure three
      dimensional changes (volumetric reduction). Lesion size correlated well with
      increasing RF energy delivery (Sperman correlation coefficient of 0.986; p =
      0.0003). Histologic assessments done serially over time (1 h through 3 weeks)
      showed a well-circumscribed lesion with a normal healing progression and no
      peripheral damage to nerves. Volumetric analysis documented a very mild initial
      edematous response that promptly tapered at 24 h. At 10 days after RF, a 26.3%
      volume reduction was documented at the treatment site (circumscribed by the
      microultrasonic crystals). CONCLUSION: RF, in a porcine animal model, can safely
      reduce tongue volume in a precise and controlled manner. Further studies will
      validate the use of RF in the treatment of OSAS.

PMID- 9149594
TI  - Dexamethasone treatment does not ameliorate subglottic ischemic injury in
      rabbits.
AB  - BACKGROUND: Following tracheal intubation, a small proportion of patients develop
      laryngeal inflammation or tissue necrosis severe enough to result in clinical
      symptoms. Although corticosteroids are frequently advocated to prevent such
      injury, human studies have been inconclusive because of the low incidence of the
      problem. This study developed a rabbit model of endotracheal tube-induced
      laryngeal injury to test the hypothesis that a corticosteroid, dexamethasone,
      could ameliorate the inflammation and necrosis. METHODS: Subglottic injury was
      induced in 21 anesthetized rabbits by inflating the cuff of an endotracheal tube
      to 100 mm Hg with the cuff just below the vocal cords. Every 30 min for 2 h, the
      cuff was deflated, the tube turned 90 degrees, and the cuff then reinflated.
      After 2 h, the rabbits' tracheas were extubated. Rabbits were divided into two
      groups: the treatment group received dexamethasone (1 mg/kg) i.v. 1 h prior to
      extubation with the dose repeated 6 h following extubation; the untreated group
      received a saline solution placebo. Four additional rabbits were anesthetized for
      the same period but did not have a tracheal tube inserted. All rabbits were
      killed 24 h later and the larynxes were harvested. Sections through the larynx at
      the level of the cricoid cartilage were randomized and submitted blindly to a
      veterinary pathologist. Larynxes were scored and ranked according to the severity
      of mucosal inflammation and necrosis, and submucosal hemorrhage, edema,
      inflammation, and necrosis. Specimens were also evaluated for focal vs diffuse
      disease. RESULTS: Injured rabbits demonstrated focal to diffuse mucosal and
      submucosal inflammation and necrosis. Inflammatory exudates were present in
      sections from most of the injured rabbits and large sections of the larynxes were
      denuded of epithelium. There were no differences in injury scores between the
      treated and untreated rabbits. The four uninjured control rabbits had normal
      larynxes. CONCLUSIONS: Two hours of endotracheal tube cuff inflation to 100 mm Hg
      causes an inflammatory laryngeal injury. The histologic features of the injury
      are unaltered by treatment with 2 mg/kg dexamethasone.

PMID- 9149595
TI  - Measuring nebulizer output. Aerosol production vs gravimetric analysis.
AB  - STUDY OBJECTIVES: The function of jet nebulizers has been measured traditionally
      by gravimetric methods, i.e., by weighing nebulizers before and after
      nebulization. Newer techniques measure aerosol output directly by analyzing
      aerosolized drug or tracer, i.e., radioactive 99mTc. Because of evaporation, the
      equivalence of these methods is uncertain. The aim of this study was to determine
      if the gravimetric method is an accurate measure of aerosol production under
      different conditions of aerosol generation (i.e., nebulizer type, flow rate,
      pressure, volume fill, and concentration of solution used to nebulize a drug).
      METHODS: In the first phase of the study, we measured the aerosol output of nine
      commercially available jet nebulizers (AvaNeb; Up-Draft-Hudson RCI; Cirrus
      Intersurgical Inc; DeVilbiss 646-DeVilbiss; Powermist-Hospitak, Inc; Respirgard
      II-Marquest Medical Products; Seamless-Seamless/Dart Respiratory; Salter; Salter
      Labs; Airlife-Baxter Health Care) run under commonly used conditions (2.5 mL
      volume fill, 2.0 mL normal saline solvent, 0.5 mL albuterol, flow of 6 L/min, and
      pressures averaging 15.0 +/- 2.3 [mean +/- SD] pounds per square inch [on the]
      gauge [psig] provided by a DeVilbiss PulmoAide compressor) with simultaneously
      measured gravimetrics and filtered radioactivity. Each nebulizer was run to
      dryness with data acquired every 2 min. The change in the weight of the nebulizer
      and radioactivity captured on the filter were expressed as percentages of the
      total in the nebulizer solution. In the second phase of the study, the
      experiments were repeated using the same nebulizers with a volume fill of 5 mL
      (diluted to half normal saline solution plus albuterol), flow of 10 L/min, and
      pressures of 35.6 +/- 8.8 psig. RESULTS: The cumulative (sum of all 2-min runs)
      weight loss for each individual nebulizer ranged from 25.00 to 64.55% and
      cumulative aerosol captured varied from 12.63 to 38.76%. While different, the
      weight loss and aerosol captured were closely correlated (y = -0.62 + 0.62x; r =
      0.961, p < 0.0001). Changing volume fill and concentration of solvent did not
      affect this correlation (p = 0.921 and 0.373, respectively). However, changing
      flow from 6 L/min to 10 L/min significantly (p = 0.02) affected the relationship
      (y = -3.80 + 0.83x; r = 0.969, p < 0.001). CONCLUSIONS: When compared with direct
      methods such as filtering generated particles, the gravimetric method of
      assessing nebulizer function overestimates aerosol output by 1.8 +/- 0.18 times,
      presumably because of the loss of solvent during nebulization. However, the
      relationship between methods is predictable and appears unaffected by changing
      the type of nebulizer, volume fill, and concentration of solvent. Changes in
      nebulizer flow and pressure significantly affected the correlation. Gravimetric
      methods can be used as simple and convenient screening techniques for comparing
      jet nebulizers under a wide range of experimental conditions.

PMID- 9149596
TI  - Combination of tracheal gas insufflation and airway pressure release ventilation.
AB  - STUDY OBJECTIVE: We hypothesized that the continuous gas flow administration
      delivered through an insufflation catheter positioned above the carina during
      airway pressure release ventilation (APRV) would facilitate carbon dioxide (CO2)
      elimination, resulting in normocarbia with a substantially reduced peak airway
      pressure (Paw). To test this hypothesis, we compared intermittent positive
      pressure ventilation (IPPV), tracheal gas insufflation (TGI), APRV, and combined
      TGI and APRV (TGI + APRV). DESIGN: Animal study with random application of four
      ventilatory modes in a canine restrictive-thorax model with and without pulmonary
      edema. SETTING: Research laboratory at Kumamoto (Japan) University School of
      Medicine. SUBJECTS: Six mongrel dogs. INTERVENTIONS: Application of four
      ventilatory modes (IPPV, TGI, APRV, and TGI + APRV). MEASUREMENTS AND RESULTS:
      TGI + APRV facilitated CO2 elimination. The peak Paw was significantly lower
      during TGI + APRV than during IPPV (nonpulmonary edema model; 15 +/- 4 vs 28 +/-
      9 cm H2O; p < 0.05; pulmonary edema model: 20 +/- 4 vs 34 +/- 10 cm H2O; p <
      0.05). Normocarbia was observed in both models. Neither TGI nor APRV alone
      maintained normocarbia. CONCLUSION: The combined use of TGI and APRV is a more
      effective method of maintaining normocarbia with reduced peak Paw than either
      IPPV or APRV alone.

PMID- 9149597
TI  - Effect of erionite on the pleural mesothelium of the Fischer 344 rat.
AB  - OBJECTIVE: This study sought to assess the fibrogenic and carcinogenic potential
      of erionite (a fibrous zeolite) on the pleural mesothelium of the Fischer 344 rat
      (n = 24). DESIGN: The study was designed to examine rat pleural mesothelial
      changes by three independent observers at timed intervals, ranging from 1 to 480
      days postinoculation using erionite from the Pine Valley, Nevada (USA) area. The
      mean length and width of the erionite fibers were 2.29 and 0.48 microns,
      respectively. Only microscopic observations made by majority (2/3) or unanimity
      (3/3) were accepted for final diagnosis. RESULTS: Pleural and lung tissue were
      available for examination in 21 of the 24 rats. Fibrosis, chronic inflammation,
      and foreign body reaction occurred in 6 of 21 rats. Mesothelial hyperplasia and
      dysplasia occurred in 9 and 3 of the 21 rats, respectively. A single mesothelioma
      was identified at 434 days in a rat that had gross nodular pleural lesions.
      CONCLUSIONS: The findings reported herein confirm the strong fibrogenic potential
      of erionite but are at variance with previous studies reporting much higher
      yields of mesothelioma. The reasons for the low yield of mesothelioma in this
      study are not known, but may be related to the study design, the strict criteria
      used for histopathologic diagnosis, and/or possible differences in erionite
      physicochemical properties, associated with its geographic distribution, most
      previous animal studies having used erionite from the Rome, Oregon (USA) area.

PMID- 9149598
TI  - Alveolar epithelial fluid clearance mechanisms are intact after moderate
      hyperoxic lung injury in rats.
AB  - The capacity of the alveolar epithelial barrier to remove excess alveolar fluid
      from the airspaces of the lung was studied in an experimental model of moderate
      hyperoxic lung injury. Rats were exposed to 100% oxygen for 40 h in an exposure
      chamber and compared with control animals exposed to room air. Extravascular lung
      water was calculated gravimetrically. Alveolar and lung liquid clearance were
      studied over 1 h by instillation of a 5% albumin solution with 1.5 microCi of
      125I-labeled albumin (6 mL/kg into both lungs). The concentration of both the
      unlabeled and labeled albumin was used to calculate alveolar liquid clearance.
      Hyperoxic rats developed pulmonary edema, with a 33% increase in extravascular
      lung water to 5.3 +/- 0.1 g of water per gram of dry lung, compared with 4.0 +/-
      0.2 g of water per gram of dry lung in control rats (p < 0.05). This degree of
      edema was associated with a significant increase in the alveolar-arterial oxygen
      difference (241 +/- 61 vs 124 +/- 14 mm Hg in control animals exposed to room
      air, p < 0.05). Despite this moderate degree of lung injury, alveolar fluid
      clearance was normal (30 +/- 3%) compared with control rats (33 +/- 6%).
      Furthermore, the hyperoxic injured rats responded normally to an exogenous beta
      adrenergic agonist (terbutaline, 10(-4) mol/L) with a 67% increase in the rate of
      alveolar liquid clearance (50 +/- 5%). Thus, in the setting of moderate hyperoxic
      lung injury, the alveolar epithelial barrier is still capable of removing fluid
      at a normal rate and responding to beta-adrenergic agonist treatment. These
      experimental results have potential clinical implications for patients with acute
      lung injury.

PMID- 9149599
TI  - The role of gastroesophageal reflux in chronic cough and asthma.

PMID- 9149600
TI  - Distinguishing left ventricular aneurysm from pseudoaneurysm. A review of the
      literature.
AB  - A postmyocardial infarction left ventricular pseudoaneurysm occurs when a rupture
      of the ventricular free wall is contained by overlying, adherent pericardium. A
      postinfarction aneurysm, in contrast, is caused by scar formation resulting in
      thinning of the myocardium. Although the usual treatment for patients with
      pseudoaneurysm is urgent surgical repair, the imaging characteristics of
      pseudoaneurysm and aneurysm, for which treatment is more conservative, are quite
      similar. The literature on the natural history and imaging characteristics of the
      two entities is reviewed, and an approach to distinguishing between the two
      entities is proposed.

PMID- 9149601
TI  - Follow-up for death or recurrence is not a reliable way of assessing the accuracy
      of diagnostic tests for thromboembolic disease.

PMID- 9149602
TI  - Cigarette smoking and lung cancer trends. A light at the end of the tunnel?
AB  - OBJECTIVE: To update the epidemic curves for lung cancer in the United States by
      gender in relation to the temporal trends in adult current cigarette smoking
      prevalence. METHODS: The design of the study was ecologic, based on population
      figures. Available data on the prevalence of current cigarette smoking from 1920
      to 1990 were plotted in conjunction with age-adjusted lung cancer mortality rates
      from 1930 to 1992 for each sex. RESULTS: There was a strong temporal relationship
      between the curves for cigarette smoking prevalence and lung cancer mortality
      rate with approximately a 30-year population latency period in both men and
      women. The curves occurred later in women than in men. The lung cancer rate in
      men peaked in 1990 and then began to decline while the rate in women continued to
      rise. CONCLUSIONS: The temporal association between cigarette smoking prevalence
      and lung cancer mortality provides additional support for the causal relationship
      between smoking and lung cancer.

PMID- 9149604
TI  - Asbestos-related disorders. A realistic perspective.

PMID- 9149603
TI  - Curative irradiation of limited endobronchial carcinomas with high-dose rate
      brachytherapy. Results of a pilot study.
AB  - OBJECTIVES OF THE STUDY: Pilot study to assess high-dose rate (HDR) brachytherapy
      as sole treatment for limited endobronchial non-small cell lung carcinomas.
      INCLUSION CRITERIA: Proximal non-small cell lung cancer in a not previously
      irradiated area, with a maximal diameter of 1 cm, no visible tumor on CT scan,
      lack of other treatment options in patients with severe, chronic respiratory
      failure, surgery, or external radiotherapy for a previous lung cancer. TREATMENT
      PROTOCOL: Treatment was based on an escalating dose protocol. Patients received
      three to five fractions of 7 Gy prescribed at 10 mm from the center of the
      applicator, once a week. RESULTS: Nineteen patients were included in this trial.
      The first two patients received three fractions of 7 Gy, the four next patients
      received four fractions, and the 13 remaining patients were treated with five
      fractions of 7 Gy. Two months after the end of the procedure, tumors in 15 of 18
      evaluable patients (83%) were locally controlled with negative results of
      biopsies. At 1 year, local control was still obtained in 12 of 16 evaluable
      patients (75%). With a mean follow-up of 28-months, 1-year and 2-year actuarial
      survival rates were 78% and 58%, respectively, with a 28-month median survival.
      One patient with local control died from hemoptysis 12 months after treatment.
      Two patients suffered from severe necrosis of the bronchial wall; one of them
      died from hemoptysis. CONCLUSIONS: HDR brachytherapy is an effective treatment
      for small endobronchial tumors. Late toxicity on the bronchial wall is still too
      high and was attributed mainly to contact between the catheter and the bronchial
      mucosa. Exclusive HDR brachytherapy should be restricted to carefully selected
      patients for whom there is no alternative curative treatment. New bronchial
      applicators and a lower dose per fraction may reduce the incidence and attenuate
      the severity of late complications.

PMID- 9149605
TI  - Diagnosis of asbestosis. Primum non nocere.

PMID- 9149607
TI  - Aortic root abscess with fistula formation.
AB  - Aortic root abscess is a common complication of aortic valve endocarditis.
      However, aortic root abscess and formation of a fistula from the aortic root to
      the right ventricular outflow tract in the setting of a native aortic valve and
      previous repair of an aortic dissection with a Dacron graft is an uncommon event.
      Transesophageal echocardiography is superior to transthoracic echocardiography
      for the diagnosis of aortic root abscess. To our knowledge, no studies have
      compared the diagnostic value of cardiac MRI with transesophageal
      echocardiography for this condition.

PMID- 9149606
TI  - Pentoxifylline does not alter the response to inhaled grain dust.
AB  - Pentoxifylline (PTX) has been shown to reduce sepsis-induced neutrophil
      sequestration in the lung and inhibit endotoxin-mediated release of tumor
      necrosis factor-alpha (TNF-alpha). Previously, we have shown that endotoxin
      appears to be the principal agent in grain dust causing airway inflammation and
      airflow obstruction following grain dust inhalation. To determine whether PTX
      affects the physiologic and inflammatory events following acute grain dust
      inhalation, 10 healthy, nonsmoking subjects with normal airway reactivity were
      treated with PTX or placebo (PL) followed by corn dust extract (CDE) inhalation
      (0.08 mL/kg), using a single-blinded, crossover design. Subjects received PTX
      (1,200 mg/d) or PL for 4 days prior to CDE inhalation and 400 mg PTX or PL on the
      exposure day. Both respiratory symptoms and declines in FEV1 and FVC occurred
      following CDE exposure in both groups, but there were no significant differences
      in the frequency of symptoms or percent declines from baseline in the FEV1 and
      FVC at any of the time points measured in the study. Elevations in peripheral
      blood leukocyte and neutrophil concentrations and BAL total cell, neutrophil, TNF
      alpha, and interleukin-8 concentrations were measured 4 h following exposure to
      CDE in both the PTX- and PL-treated subjects, but no significant differences were
      found between treatment groups. These results suggest that pretreatment with PTX
      prior to inhalation of CDE, in the doses used in this study, does not alter the
      acute physiologic or inflammatory events following exposure to inhaled CDE.

PMID- 9149608
TI  - A 77-year-old man with a lung mass.

PMID- 9149609
TI  - Persistent pulmonary infiltrate and bronchorrhea in a young woman.

PMID- 9149610
TI  - Very early onset of acute amiodarone pulmonary toxicity presenting with
      hemoptysis.
AB  - A case of amiodarone pulmonary toxicity (APT) occurring within days of the start
      of therapy and presenting with hemoptysis is reported. Both the very early onset
      and the presenting symptom are highly unusual in this entity. Implications in the
      diagnosis of APT are discussed.

PMID- 9149611
TI  - Catamenial hemoptysis. Diagnosis with MRI.
AB  - Thoracic endometriosis is a rare disorder. We report a case of a 26-year-old
      woman with a 4-year history of catamenial hemoptysis due to thoracic
      endometriosis which was diagnosed by MRI and treated successfully by means of
      video-assisted thoracoscopic wedge-resection of the solitary pulmonary lesion.
      Medical therapy with hormones was not necessary. There is no evidence of
      recurrence 10 months after the operation. This case demonstrates that MRI of the
      chest may be considered for the diagnostic work-up of patients with catamenial
      hemoptysis. It also shows that wedge-resection of pulmonary endometriosis foci by
      means of video-assisted thoracoscopy-an approach that has not been described in
      the literature thus far-is an effective therapy in localized peripheral pulmonary
      parenchymal endometriosis.

PMID- 9149612
TI  - Immediate transcatheter embolization of Swan-Ganz catheter-induced pulmonary
      artery pseudoaneurysm.
AB  - Digital subtraction angiography is an indispensable complement to cut film
      studies for the detection of pulmonary artery injury. Immediate transcatheter
      embolization of catheter-induced pulmonary artery pseudoaneurysm is a safe,
      minimally invasive, fast, and cost-effective alternative to surgical treatment.

PMID- 9149613
TI  - Management of bronchopleural fistula with a variable-resistance valve and a
      single ventilator.
AB  - Independent lung ventilation with two ventilators is sometimes used in the
      management of bronchopleural fistula (BPF). We describe a patient in whom gas
      flow through a large BPF was initially reduced, and subsequently eliminated,
      during differential lung ventilation using a single ventilator and a variable
      resistance valve attached to one lumen of a bifurcated endotracheal tube.

PMID- 9149614
TI  - Nonsustained polymorphous ventricular tachycardia during amiodarone therapy for
      atrial fibrillation complicating cardiomyopathy. Management with intravenous
      magnesium sulfate.
AB  - A case is presented in which amiodarone was administered to suppress paroxysmal
      atrial fibrillation in a patient with an idiopathic cardiomyopathy. Eleven days
      after initiation of therapy with amiodarone, the patient experienced syncope and
      was noted to have recurrent episodes of polymorphous ventricular tachycardia. The
      patient was hospitalized and treated with a bolus as well as continuous infusion
      of intravenous magnesium sulfate. When the infusion was transiently discontinued,
      recurrences of polymorphous ventricular tachycardia were noted. The probable
      proarrhythmic action of amiodarone, although rare, is reviewed along with a
      discussion of the novel use of intravenous magnesium sulfate therapy.

PMID- 9149615
TI  - Recurrent alveolar proteinosis following double lung transplantation.
AB  - We present a case of recurrent alveolar proteinosis following double lung
      transplantation.

PMID- 9149616
TI  - Pulmonary tuberculosis after lung transplantation.
AB  - During a 5-year study period, we diagnosed pulmonary tuberculosis in two (2%) of
      94 lung and heart-lung transplant recipients. Each infection occurred 3 months
      after bilateral lung transplantation in the presence of evidence implicating
      donor-to-recipient transmission of the pathogen. The radiographic patterns of
      pulmonary tuberculosis were subtle: narrowing of the middle lobe bronchus of the
      right lung caused by an endobronchial granulomatous mass (n = 1) and a focal
      cluster of small nodules in the upper lobe of the left lung and small bilateral
      pleural effusions (n = 1). Each patient achieved complete clinical and
      radiographic response after antituberculous therapy. We conclude that
      Mycobacterium tuberculosis may be transmitted directly by a donor lung and may
      involve bronchial mucosa, pulmonary parenchyma, and pleura.

PMID- 9149617
TI  - Idiopathic myocardial vasculitis presenting as restrictive cardiomyopathy.
AB  - A previously unreported case of small-vessel myocardial vasculitis presenting as
      restrictive cardiomyopathy and congestive heart failure is described. The
      hemodynamic study, showing severely increased and equalized diastolic pressures
      in atrial and ventricular chambers, and cardiac MRI, showing normal pericardium
      and ventricular endomyocardial biopsy, not including myocardial vascular
      component, were insufficient to make a diagnosis. This made a thoracotomy and
      surgical cardiac biopsy necessary. Steroids and cyclophosphamide, introduced
      after histologic evidence of necrotizing vasculitis, unassociated with a systemic
      disease, became available and improved the clinical profile and the diastolic
      dysfunction at two-dimensional echocardiographic Doppler analysis.

PMID- 9149618
TI  - Pulmonary artery flotation catheters. Better late than never?

PMID- 9149619
TI  - Assessment of oxygen uptake during the six-minute walk test. The author responds.

PMID- 9149620
TI  - Aging effects on swallowing reflex.

PMID- 9149621
TI  - The critical age that the young start the devastating habits of smoking and
      narcotics.

PMID- 9149622
TI  - Peripartum pleural effusion.

PMID- 9149623
TI  - Airway obstruction with percutaneous tracheostomy.

PMID- 9149624
TI  - Fatal pneumothorax complicating BAL in a bone marrow transplant recipient with
      bronchiolitis obliterans.

PMID- 9149625
TI  - Use of pulsed-wave Doppler echocardiography to measure changes in MPAP. Is
      further validation required?

PMID- 9149626
TI  - Noninvasive measurement of pulmonary arterial blood velocity. Can it replace
      right heart catheterization?

PMID- 9149627
TI  - Why be limited to nocturnal noninvasive IPPV?

PMID- 9149628
TI  - Steroid-responsive interstitial pneumonitis after fludarabine therapy.

PMID- 9149629
TI  - Objective response to epirubicin and lonidamine. A case of advanced thymoma
      previously treated with the ADOC scheme and unresponsive to paclitaxel plus
      cyclophosphamide.

PMID- 9149631
TI  - The role of intermittent enteral feeding in reducing gastric colonization in
      mechanically ventilated patients.

PMID- 9149630
TI  - Sampling arterial blood with a fine needle.

PMID- 9149632
TI  - Another important detail of percutaneous dilatational tracheostomy technique.

PMID- 9149633
TI  - HIV databases and flowcharts are useful tools ... but.

PMID- 9149634
TI  - Reading and evaluating clinical review articles.

PMID- 9149635
TI  - Different viewpoints on alternative medicine.

PMID- 9149636
TI  - Different viewpoints on alternative medicine.

PMID- 9149637
TI  - Different viewpoints on alternative medicine.

PMID- 9149638
TI  - Different viewpoints on alternative medicine.

PMID- 9149639
TI  - Sorbitol-based elixirs, diarrhea and enteral tube feeding.

PMID- 9149640
TI  - Safety in the day care setting.

PMID- 9149641
TI  - Nails and nail disorders in children and adults.
AB  - Abnormalities of the nails can provide both subtle and obvious clues to common
      medical problems or severe systemic diseases. Heredity, minor injuries and a
      variety of infections account for many changes in the appearance of nails.
      Several dermatologic disorders, such as psoriasis and alopecia areata, and other
      multisystem disorders may present with nail changes; abnormalities of the nails
      may be the single most prominent feature. Common habits and the use of various
      cosmetics also may result in nail changes. Awareness of normal nail variants and
      well-defined abnormalities and their disease associations will be beneficial to
      most clinicians. Specific management and therapy for most nail problems are
      usually simple and appropriate for primary care physicians.

PMID- 9149642
TI  - Evaluation and management of diabetes insipidus.
AB  - Diabetes insipidus is an uncommon condition characterized by polyuria and
      polydipsia. The symptoms and biochemical changes of this condition result from
      either a lack of antidiuretic hormone or renal insensitivity to its effect.
      Failure to produce or release antidiuretic hormone may result from cranial
      pathology, including trauma and surgery. The renal insensitivity to antidiuretic
      hormone that occurs in patients with nephrogenic diabetes insipidus may be caused
      by genetic factors, drugs (especially lithium) or specific disease processes.
      Patients may compensate for polyuria and nocturia by excessive water intake but
      show marked decreases in urine specific gravity and osmolality. Patients with
      severe and uncompensated symptoms develop marked dehydration, neurologic symptoms
      and encephalopathy. The water deprivation test is useful in diagnosing diabetes
      insipidus and in differentiating neurogenic from nephrogenic cases. Neurogenic
      diabetes insipidus may respond to nasal administration of desmopressin.
      Nephrogenic diabetes insipidus requires good hydration and monitoring of body
      chemistry. Thiazides and amiloride may relieve symptoms.

PMID- 9149643
TI  - Getting the most from review articles: a guide for readers and writers.
AB  - A good medical review article is easily readable and pares down the seemingly
      overwhelming amount of information available in the literature. The research
      experience and clinical expertise of the writer do not guarantee valid and
      relevant recommendations. Uncritical acceptance of information by readers further
      potentiates the dissemination of misinformation. Only through teamwork, with each
      partner--both writer and reader--taking responsibility for a role, can review
      articles result in improved patient care. This article offers guidance to both
      consumers and producers--readers and writers-of review articles.

PMID- 9149644
TI  - Standardized forms to use in the management of HIV infection.
AB  - Family physicians should be prepared to care for the increasing number of
      patients infected with human immunodeficiency virus (HIV) and those who have
      acquired immunodeficiency syndrome. Strategies are needed to help practicing
      physicians become more competent in the medical care of patients with HIV
      infection and AIDS. This article introduces three forms that can serve as
      templates for the physician to use in evaluating and managing patients with HIV
      infection. These forms incorporate current recommendations for monitoring
      patients and cue the physician to consider specific prevention strategies.

PMID- 9149645
TI  - Exercise prescription for chronically ill patients.
AB  - Although patients with chronic illnesses typically refrain from exercise, many of
      them could benefit significantly from mild, long-term exercise therapy. While
      factors such as pain or weakness often discourage the chronically ill person from
      being physically active, lack of motivation and lack of knowledge are the primary
      obstacles. An effective way of overcoming these obstacles is to provide an
      individualized exercise regimen that both motivates and instructs. Patients who
      receive an exercise prescription enjoy this individualized approach, tend to
      exercise safely and quickly become aware of the benefits of exercise therapy as
      an adjuvant to their medical treatment.

PMID- 9149646
TI  - Vacuum-assisted vaginal delivery.
AB  - Vacuum extraction is an effective method of operative vaginal delivery. The
      procedure is widely used in Europe and many developing countries as the
      instrument of choice for assisted vaginal deliveries and has recently gained
      greater acceptance in the United States. The vacuum procedure is relatively easy
      to learn and offers a safer, less traumatic alternative to the use of forceps or
      cesarean section for indicated deliveries. Advances in extractor cup design have
      resulted in fewer cases of neonatal and maternal trauma and improved efficacy. As
      with any procedure, strict attention to technique and sound clinical judgment are
      essential for success.

PMID- 9149647
TI  - The painful foot, Part II: Common rearfoot deformities.
AB  - As with deformities of the forefoot, deformities of the rearfoot often respond
      well to conservative therapy. Rest and nonsteroidal anti-inflammatory medications
      are often used. Patients with plantar fasciitis may benefit from corticosteroid
      injections. Surgery may be helpful in refractory cases. Haglund's deformity is
      associated with pain in the area of the osseous ridge on the posterosuperior
      aspect of the calcaneus. The retrocalcaneal bursa may be inflamed. This disorder
      is diagnosed by palpation of the painful area. Conservative treatment consists of
      minimizing pressure over the osseous ridge. Corticosteroid injection is not
      advised since it may weaken the Achilles tendon. Surgical intervention consists
      of resection or reduction of the osseous ridge. Posterior calcaneal spur is
      another cause of heel pain. The spur can be visualized radiographically in the
      tendon insertion. Treatment is conservative, with footgear modification and
      nonsteroidal anti-inflammatory drug therapy. Surgery to remove the spur may be
      indicated if conservative measures fall to relieve the pain. Tarsal tunnel
      syndrome is characterized by pain and numbness from the medial malleolus to the
      sole of the foot. Conservative treatment includes reducing abnormal pronation
      with an orthosis.

PMID- 9149648
TI  - Management of radial head fracture.
AB  - A fracture involves not only bone, but also surrounding soft tissues. Attention
      to soft tissue injury may help prevent long-term complications such as
      contractures, weakness, instability and loss of proprioception. Appropriate
      treatment is directed at three phases of healing: inflammation, repair and
      remodeling. The two- to seven-day inflammatory phase is controlled with rest,
      ice, elevation, immobilization and medications to reduce the pain and swelling.
      Immobilization during the two- to eight-week repair phase promotes bone healing
      but may lead to contractures and loss of strength if continued for too long.
      Physical therapy during the several-month remodeling phase helps restore
      strength, range of motion and proprioception. Although six to eight weeks is a
      usual estimate for fracture healing, the actual time can be affected by the type
      of fracture and the person's age, nutritional and health status, and medication
      use. This review of the diagnosis and treatment of radial head fractures
      illustrates the importance of directing the treatment toward the three phases of
      healing.

PMID- 9149649
TI  - Endoscopic ultrasonography: a new diagnostic imaging modality.
AB  - Endoscopic ultrasonography uses high-frequency ultrasound to visualize the gut
      wall and the surrounding structures of the mediastinum, the abdomen and the
      pelvis. Echoendoscopes are available in two different designs. A radial scanning
      echoendoscope produces a 360 degree real-time view perpendicular to the shaft of
      the echoendoscope. A linear-array instrument produces a 100 degrees real-time
      view parallel to the shaft of the echoendoscope, permitting direct
      ultrasonographic guidance of fine needles exiting the biopsy channel. Endoscopic
      ultrasonography has been established as the preferred diagnostic tool for the
      evaluation of submucosal masses of the upper gastrointestinal tract and the
      rectosigmoid, for differentiating benign from pathologic thickened gastric folds
      and for locating pancreatic endocrine tumors. The widest application of
      endoscopic ultrasonography is in the diagnosis and staging of esophageal,
      gastric, rectal and pancreaticobiliary neoplasms. Endosonography is the most
      accurate modality available for determining the T and N stages of these tumors.
      The recent development of endoscopic ultrasound-guided fine-needle aspiration
      provides physicians with the ability to cytologically diagnose lesions visualized
      endosonographically and to confirm cancer staging with tissue.

PMID- 9149650
TI  - Fecal incontinence in children.
AB  - Functional constipation is the cause of fecal incontinence in 95 percent of
      affected children, and anatomic or neurologic causes account for up to 5 percent
      of cases. The history and the physical examination (with emphasis on abdominal,
      rectal and neurologic examinations) are most helpful in identifying organic
      disease. In some children, anorectal manometry, a barium enema radiographic
      examination and a rectal biopsy are necessary to determine the etiology. Most
      children with fecal incontinence benefit from a strict treatment plan that
      includes defecation trials, a fiber-rich diet and laxative medications. Surgery
      followed by medical treatment is required in patients with Hirschsprung's disease
      and in some patients with anal stenosis or a history of surgical repair of an
      anorectal malformation.

PMID- 9149651
TI  - Captopril renal scintigraphy in renovascular hypertension.
AB  - Renovascular disease is a common cause of secondary hypertension. Renal artery
      stenosis is present in up to one third of patients with clinical markers
      suggestive of renovascular hypertension, such as hypertension refractory to
      medical management, severe hypertension in a young patient and worsening of renal
      function after the use of an angiotensin-converting enzyme inhibitor. Early
      discovery of renal artery stenosis may allow amelioration or cure of the
      hypertension and halt progressive loss of renal function. Although renal
      arteriography remains the gold-standard aid to diagnosis and to planning surgical
      intervention, it is an invasive procedure that may cause deterioration of renal
      function. In the presence of renal artery stenosis, glomerular filtration is
      maintained by angiotensin. Administration of captopril in renal scintigraphy
      removes this compensatory mechanism and causes a temporary impairment of renal
      function in the affected kidney. Nuclear tracers can visualize this impairment,
      thus allowing assessment of the physiologic significance of a renal artery
      stenosis. The test can be done as a outpatient procedure.

PMID- 9149652
TI  - Prevention of coronary heart disease through cholesterol reduction.
AB  - Growing evidence suggests that lowering serum cholesterol levels, particularly
      low-density lipoprotein levels, will reduce the risk for coronary heart disease.
      The benefit of cholesterol-lowering therapy has been documented by many clinical
      trials. Two secondary prevention trials, the Scandinavian Simvastatin Survival
      Study and the Cholesterol and Recurrent Events trial, demonstrated a striking
      reduction in recurrent coronary heart disease without an increase in
      noncardiovascular mortality; treatment with simvastatin reduced total mortality
      by 30 percent. A primary prevention trial, the West of Scotland Coronary
      Prevention Study, demonstrated similar results in high-risk patients without
      established coronary heart disease. More recent angiographic trials revealed that
      cholesterol-lowering therapy will reduce progression of atherosclerosis and, in
      some cases, will reverse existing lesions. Use of HMG-CoA reductase inhibitors
      also appears to be beneficial and safe. Evidence supports cholesterol-lowering
      therapy in high-risk patients, both with and without established atherosclerotic
      disease.

PMID- 9149653
TI  - Cervical angina.
AB  - Cervical angina is defined as chest pain that resembles true cardiac angina but
      originates from a cervical discopathy with nerve root compression. This
      condition, which is also referred to as pseudoangina, most commonly results from
      compression of the C7 nerve root. Several simple findings from the history and
      the physical examination help make the diagnosis, which can then be confirmed
      with magnetic resonance imaging and/or discography. Coexisting coronary artery
      disease must always be ruled out. Treatment includes intermittent cervical
      traction, physical therapy, nonsteroidal anti-inflammatory drugs and muscle
      relaxants. If these measures fall to alleviate the patient's pain, referral to a
      spine surgeon may be indicated.

PMID- 9149654
TI  - Chemotherapy in the treatment of non-small cell lung cancer.
AB  - Non-small cell cancers of the lung include squamous cell carcinoma,
      adenocarcinoma and large cell carcinoma. These tumors have traditionally been
      considered to be quite resistant to both chemotherapy and radiation therapy.
      Although surgery has offered the best chance for cure, the tumor has usually
      spread too far for effective surgery by the time it is discovered. Several newer
      chemotherapeutic agents show improved survival rates in the treatment of these
      tumors. These agents include paclitaxel, carboplatin and vinorelbine. These drugs
      may be used as single agents or in combination and have also been used in
      combination with radiation. Although further study will be required before the
      optimal regimen is determined, it appears that use of these agents can improve
      the survival of patients with inoperable non-small cell cancer of the lung.

PMID- 9149655
TI  - NHLBI issues update on task force report on high blood pressure in children and
      adolescents.
AB  - Health-related behaviors that reduce the risk of cardiovascular disease should be
      encouraged for all children and their families. Physicians should monitor blood
      pressure, counsel patients about appropriate nutrition and exercise, and
      emphasize the importance of not smoking. Because black adults in the United
      States have an increased prevalence, morbidity and mortality of essential
      hypertension, the working group advises physicians to be particularly vigilant in
      monitoring blood pressure in black children, especially those with a family
      history of hypertension. Other groups with a higher prevalence of hypertension
      and any person with a family history of hypertension should be monitored closely.

PMID- 9149657
TI  - CDC data on AIDS.

PMID- 9149656
TI  - ACOG report targets nutrition in women. American College of Obstetricians and
      Gynecologists.

PMID- 9149658
TI  - Distribution and association of chronic disease and mobility difficulty across
      four body mass index categories of African-American women.
AB  - A majority of African-American women over the age of 50 are obese, have at least
      one chronic disease, and experience mobility difficulty. Using self-reported data
      from the 1992 Health and Retirement Study of 1,150 African-American women aged 30
      70 years, this report first compares chronic disease prevalence and severity,
      pain, sensory deficits, and mobility difficulty across four categories of body
      mass index and, second, investigates whether body mass index affects the
      association of chronic disease with mobility difficulty. Body mass index was
      categorized as low, medium, high, and severe, being equal to 19-24 (20%), 25-29
      (38%), 30-34 (24%), and 35 or over (18%), respectively. There were few
      differences when comparing the medium category with either the low or high
      category. Those in the severe body mass index category, however, reported
      significantly more frequent and severe hypertension, diabetes, cancer, heart
      disease, arthritis, pain, sensory deficits, and mobility difficulty than did
      those in the medium body mass index category. Obesity did not appear to affect
      the association between chronic disease and mobility difficulty. The relatively
      high rates of mobility difficulty observed among the severe body mass index group
      appear to be more likely a result of relatively high chronic disease prevalence
      and severity than to a disproportionate impact of these on mobility.

PMID- 9149659
TI  - Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish
      men. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study.
AB  - The relation of intakes of specific fatty acids and the risk of coronary heart
      disease was examined in a cohort of 21,930 smoking men aged 50-69 years who were
      initially free of diagnosed cardiovascular disease. All men participated in the
      Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study and completed a
      detailed and validated dietary questionnaire at baseline. After 6.1 years of
      follow-up from 1985-1988, the authors documented 1,399 major coronary events and
      635 coronary deaths. After controlling for age, supplement group, several
      coronary risk factors, total energy, and fiber intake, the authors observed a
      significant positive association between the intake of trans-fatty acids and the
      risk of coronary death. For men in the top quintile of trans-fatty acid intake
      (median = 6.2 g/day), the multivariate relative risk of coronary death was 1.39
      (95% confidence interval (CI) 1.09-1.78) (p for trend = 0.004) as compared with
      men in the lowest quintile of intake (median = 1.3 g/day). The intake of omega-3
      fatty acids from fish was also directly related to the risk of coronary death in
      the multivariate model adjusting also for trans-saturated and cis-monounsaturated
      fatty acids (relative risk (RR) = 1.30, 95% CI 1.01-1.67) (p for trend = 0.06 for
      men in the highest quintile of intake compared with the lowest). There was no
      association between intakes of saturated or cis-monounsaturated fatty acids,
      linoleic or linolenic acid, or dietary cholesterol and the risk of coronary
      deaths. All the associations were similar but somewhat weaker for all major
      coronary events.

PMID- 9149660
TI  - Tracking of risk factors for coronary heart disease over a 14-year period: a
      comparison between lifestyle and biologic risk factors with data from the
      Amsterdam Growth and Health Study.
AB  - Because the magnitude of tracking coefficients (i.e., stability coefficients and
      tracking for subjects at risk) greatly depends on the initial age of subjects,
      the number and spacing of longitudinal measurements, and the length of the total
      time period, it is difficult to compare tracking coefficients from different
      studies with each other. Because in the Amsterdam Growth and Health Study both
      biologic (i.e., lipoproteins, blood pressure, body fatness, and cardiopulmonary
      fitness) and lifestyle (i.e., dietary intake, daily physical activity, smoking,
      and alcohol consumption) risk factors for coronary heart disease were measured,
      this study gives the unique possibility of comparing tracking coefficients of
      biologic and lifestyle risk factors within one data set. In the Amsterdam Growth
      and Health Study, six repeated measurements were carried out on 181 subjects over
      a period from 13 to 27 years of age, beginning in 1977. The results indicated
      that, over a period of 14 years covering adolescence and young adulthood, both
      stability coefficients and tracking for subjects at risk for lifestyle risk
      factors were low (except for smoking), indicating low predictability of early
      measurements for values later in life. For the biologic risk factors
      cardiopulmonary fitness and blood pressure, tracking was also low, while for the
      lipoproteins and body fatness, tracking was much better, indicating good
      predictability.

PMID- 9149661
TI  - Heart rate variability from short electrocardiographic recordings predicts
      mortality from all causes in middle-aged and elderly men. The Zutphen Study.
AB  - Low heart rate variability is associated with high risk of sudden death in
      myocardial infarction patients. This has been attributed to unfavorable autonomic
      cardiac control. In the present study, the predictive value of heart rate
      variability for sudden death, mortality from coronary heart disease, and from all
      causes was investigated in the general population, using brief
      electrocardiographic recordings. From 1960 to 1985, 878 middle-aged Dutch men,
      aged 40-60 years, were followed and repeatedly examined as part of the Zutphen
      Study. In 1985 the remaining cohort was extended to 885 elderly men, aged 65-85
      years, and followed until 1990. Heart rate variability (standard deviation of
      duration of normal RR intervals) was determined from the resting 12-lead
      electrocardiogram. The 5-year age-adjusted relative rate of total mortality of
      men with heart rate variability of < 20 milliseconds (msec) compared with men
      with heart rate variability of 20-39 msec was 2.1 (95 percent confidence interval
      1.4-3.0) in middle-aged men and 1.4 (95% confidence interval 0.9-2.2) in elderly
      men. Death from noncoronary causes, especially cancer, contributed significantly
      to this elevated risk. The association of low heart rate variability with sudden
      death or coronary heart disease mortality was less consistent. In conclusion, in
      middle-aged men and probably in elderly men, low heart rate variability is
      predictive of mortality from all causes. This suggests that low heart rate
      variability is an indicator of compromised health in the general population.

PMID- 9149662
TI  - Alcohol intake and insulin levels. The Normative Aging Study.
AB  - Much remains to be clarified in the apparently protective effect of moderate
      alcohol use against coronary heart disease risk. Insulin levels are positively
      associated with coronary heart disease risk, so recent reports of decreased
      insulin sensitivity among nondrinkers and lower fasting insulin levels with
      increasing alcohol intake suggest the possibility that insulin may play a role.
      Between 1987 and 1991, the authors examined fasting insulin concentrations and
      the empiric fasting insulin resistance index in relation to reported alcohol
      intake (mean, 15.3 g/day; standard deviation, 19.6; range, 0-120.6) and potential
      confounders. The latter included age, obesity, fat distribution, smoking, energy,
      saturated fat intake, antihypertensive medication, and physical activity.
      Participants in this cross-sectional analysis were 938 nondiabetic men from the
      Boston, Massachusetts, area who were part of the Normative Aging Study.
      Unadjusted fasting insulin levels were significantly different (p = 0.008)
      between categories of alcohol intake, as were fasting insulin resistance index
      values (p = 0.01). After adjustment for potential confounders, analysis revealed
      that subjects consuming moderate amounts of alcohol had the lowest fasting
      insulin and fasting insulin resistance index values. Compared with values from
      moderate drinkers, fasting insulin resistance index values were higher in those
      subjects reporting no alcohol intake (p = 0.011), low intake (p = 0.004), and
      high intake (p = 0.04). A similar pattern was observed for fasting insulin
      values. Among this sample of nondiabetic men, moderate drinkers had the lowest
      levels of fasting insulin resistance index and fasting insulin, consistent with
      lower levels of insulin resistance and thus lower risk for coronary heart
      disease. These findings suggest the possibility that the coronary heart disease
      protective effects of moderate alcohol use are at least partially mediated by
      insulin.

PMID- 9149663
TI  - Comparison of effect estimates from a meta-analysis of summary data from
      published studies and from a meta-analysis using individual patient data for
      ovarian cancer studies.
AB  - To determine the relative merits of two quantitative methods used to estimate the
      summary effects of observational studies, the authors compared two methods of
      meta-analysis. Each quantified the relation between oral contraceptive use and
      the risk for ovarian cancer. One analysis consisted of a meta-analysis using
      summary data from 11 published studies from the literature (MAL) in which the
      study was the unit of analysis, and the second consisted of a meta-analysis using
      individual patient data (MAP) in which the patient was the unit of analysis. The
      authors found excellent quantitative agreement between the summary effect
      estimates from the MAL and the MAP. The MAP permits analysis 1) among outcomes,
      exposures, and confounders not investigated in the original studies, 2) when the
      original effect measures differ among studies and cannot be converted to a common
      measure (e.g., slopes vs. correlation coefficients), and 3) when there is a
      paucity of studies. The MAL permits analysis 1) when resources are limited, 2)
      when time is limited, and 3) when original study data are not available or are
      available only from a biased sample of studies. In public health epidemiology,
      data from original studies are often accessible only to limited numbers of
      research groups and for only a few types of studies that have high public health
      priority. Consequently, few opportunities for pooled analysis exist. However,
      from a policy view, MAL will provide answers to many questions and will help in
      identifying questions for future investigation.

PMID- 9149665
TI  - Incidence of functional decline and improvement in a community-dwelling, very
      elderly population.
AB  - With the aging of the population, functional decline is one of the major
      challenges to health care systems. The objective of this study was to estimate
      the incidence of functional decline and improvement in a community-dwelling
      population of people aged 75 years and above. A representative sample of elderly
      people living at home in the city of Sherbrooke (Quebec, Canada) was assessed
      yearly on three occasions (1991-1993) by a nurse. Disabilities were measured by
      the Functional Autonomy Measurement System, a 29-item rating scale developed
      according to the World Health Organization classification of disabilities. From
      the 655 subjects who agreed to participate, a total of 572 subjects completed the
      study, including 68 who subsequently died. The probability of declining was 20.1%
      for the first year and 12.4% for the second year. The incidence of functional
      decline among previously stable subjects was 11.9% (95% confidence interval (CI)
      8.9-15.9). Age was strongly related to decline (relative risk (RR) = 1.15/year,
      95% CI 1.09-1.21), but there was no significant sex effect (RRmale = 0.88, 95% CI
      0.55-1.39). The incidence of improvement among previously disabled subjects was
      estimated at 7.5% (95% CI 5.1-10.9) for the first year and 17.9% (95% CI 14.0
      23.0) for the second year. Neither age (RR = 1.07, 95% CI 0.99-1.15) nor sex
      (RRmale = 1.70, 95% CI 0.90-3.18) was significantly associated with the
      probability of improving. This study stresses the importance of precise
      measurement of disabilities and the complex and dynamic process of functional
      transitions.

PMID- 9149664
TI  - Calcium intake and fracture risk: results from the study of osteoporotic
      fractures.
AB  - The relation between dietary calcium, calcium, and vitamin D supplements and the
      risk of fractures of the hip (n = 332), ankle (n = 210), proximal humerus (n =
      241), wrist (n = 467), and vertebrae (n = 389) was investigated in a cohort study
      involving 9,704 US white women aged 65 years or older. Baseline assessments took
      place in 1986-1988 in four US metropolitan areas. Dietary calcium intake was
      assessed at baseline with a validated food frequency questionnaire. Data on new
      nonvertebral fractures were collected every 4 months during a mean of 6.6 years
      of follow-up; identification of new vertebral fractures was based on comparison
      of baseline and follow-up radiographs of the spine done a mean of 3.7 years
      apart. Results were adjusted for numerous potential confounders, including
      weight, physical activity, estrogen use, protein intake, and history of falls,
      osteoporosis, and fractures. There were no important associations between dietary
      calcium intake and the risk of any of the fractures studied. Current use of
      calcium supplements was associated with increased risk of hip (relative risk =
      1.5, 95% confidence interval 1.1-2.0) and vertebral (relative risk = 1.4, 95%
      confidence interval 1.1-1.9) fractures; current use of Tums antacid tablets was
      associated with increased risk of fractures of the proximal humerus (relative
      risk = 1.7, 95% confidence interval 1.3-2.4). There was no evidence of a
      protective effect of vitamin D supplements. Although a true adverse effect of
      calcium supplements on fracture risk cannot be ruled out, it is more likely that
      our findings are due to inadequately controlled confounding by indications for
      use of supplements. In conclusion, this study did not find a substantial
      beneficial effect of calcium on fracture risk.

PMID- 9149667
TI  - Reflections on telomeres, growth, aging, and essential hypertension.
AB  - Here we review the "telomere hypothesis of cellular aging." We propose that this
      hypothesis is relevant to our understanding of the roles of genetics as well as
      growth and development in the etiology of essential hypertension and its
      cardiovascular complications. Elements of this hypothesis and the speculations
      that we make can be directly tested using tissues (cells) obtained from human
      beings.

PMID- 9149666
TI  - Dose- and time-dependent relations between infective Anopheles inoculation and
      outcomes of Plasmodium falciparum parasitemia among children in western Kenya.
AB  - Blood-stage level Plasmodium falciparum infection (parasitemia density) is
      generally elevated prior to, or at the time of, clinical presentation of severe
      pediatric malaria episodes. Intensity of exposure to infective Anopheles mosquito
      bites is a suspected determinant of higher density parasitemia. Analyses of
      entomologic and parasitologic data collected in 1986-1987 were conducted to
      investigate whether the dose of infective bites predicted the incidence or degree
      of P. falciparum parasitemia in Kenyan children < 6 years old. At 21 consecutive
      30-day intervals, a new cohort (n approximately 50 each) was enrolled, cured of
      malaria parasites, and monitored over 84 days for recurrent parasitemia. Outcomes
      included time to parasitemia, time to parasitemia > or = 5,000/microliter, and
      parasitemia density. Ecologic and individual-level analyses were conducted. The
      mean infective bite exposure experienced by each cohort was significantly
      associated with the incidence of parasitemia (age-adjusted r2 = 0.38, p = 0.022)
      and more strongly associated with the incidence of parasitemia > or =
      5,000/microliter (age-adjusted r2 = 0.72, p < 0.001). The infective bite dose,
      analyzed as a time-dependent covariate, was associated with a 2.8 times higher
      rate of parasitemia > or = 5,000/microliter among children exposed to > or = 1
      infective bite per day as compared with the referent (rate ratio (RR) = 2.82, 95%
      confidence interval (CI) 2.24-3.56). Cumulative infective bite exposure, exposure
      duration, and age were significant predictors of recurrent parasitemia density in
      multiple linear regression analyses. The results support the contention that
      reductions in P. falciparum transmission intensity, in the absence of complete
      elimination, will reduce higher level parasitemia among African children.

PMID- 9149668
TI  - Angiotensinogen gene variation associated with variation in blood pressure in
      aboriginal Canadians.
AB  - We measured blood pressure and related clinical phenotypes in 497 adult native
      Canadians from an isolated community in Northern Ontario. We analyzed their DNA
      for genotypes of angiotensinogen. We found that the frequency of the T235 variant
      of the angiotensinogen gene was 0.89 in this sample. This variant was associated
      with a significantly increased systolic pressure but not diastolic pressure. We
      also found that sex and body mass were each highly significantly associated with
      variation in both systolic and diastolic pressures. We found a significant
      association between age and variation in systolic pressure but not diastolic
      pressure. We also found a highly significant association between plasma
      apolipoprotein B concentration and variation in diastolic pressure but not
      systolic pressure. The high frequency of the angiotensinogen T235 variant
      suggests that subjects in this young, essentially normotensive population might
      be predisposed to hypertension, which may become more apparent in the presence of
      secondary factors.

PMID- 9149669
TI  - Association of the angiotensinogen gene to serum angiotensinogen in blacks and
      whites.
AB  - A variant of the angiotensinogen gene (AGT) that encodes for threonine at codon
      235 (T235) has been associated with a higher serum angiotensinogen concentration
      and with hypertension in white subjects. The frequency of T235 is about two times
      higher in blacks than whites, suggesting that AGT may contribute to the
      susceptibility to hypertension in blacks more than it does in whites. However, an
      association of T235 with angiotensinogen level or blood pressure has not been
      observed in blacks, possibly because the high prevalence of T235 makes it
      insufficiently informative as a marker. For this reason, we undertook to further
      differentiate the T235 carrier state by constructing haplotypes with alleles in
      the 5' upstream region of AGT. One such haplotype, -1074t;T235, showed a
      significant association with angiotensinogen level in a cohort of black and white
      children and adolescents (76 blacks, mean age = 12.3 +/- 2.0 [SD] years; 139
      whites, mean age = 12.4 +/- 1.8 years). With a linear regression model, the level
      of serum angiotensinogen was significantly related to body mass index (P = .0017)
      and the haplotype (P = .0001). Within specific race groups, the haplotype was
      significantly related to serum angiotensinogen in both the blacks (P = .0277) and
      whites (P = .0001). The mean level of angiotensinogen was higher in the blacks
      carrying a single copy of the haplotype than in those without the haplotype
      (1472.2 +/- 68.4 versus 1274.9 +/- 46.7 nmol angiotensin I/L), a difference that
      was marginally significant (P = .0609). In the whites, the level of
      angiotensinogen was also higher in carriers of a single copy than in those with
      no copy (1527.9 +/- 71.2 versus 1099.2 +/- 20.1 nmol angiotensin I/L) (P =
      .0003). Serum angiotensinogen level did not increase with two copies of the
      haplotype, but in each racial group, there were only four individuals who were
      homozygous. The haplotype showed a marginally significant relation (P = .0757) to
      the mean of longitudinally determined diastolic pressures adjusted for body mass
      index, race, sex, and age. In summary, using a haplotype to differentiate further
      the T235 carrier state, we observed an association of genotype with serum
      angiotensinogen level and blood pressure in blacks and whites. The findings
      suggest that AGT may play an important role in blood pressure regulation in both
      racial groups.

PMID- 9149670
TI  - Reduced dietary potassium reversibly enhances vasopressor response to stress in
      African Americans.
AB  - Acute vasopressor responses to stress are adrenergically mediated and hence
      potentially subject to differential modulation by dietary potassium and sodium.
      The greater vasopressor responsiveness in blacks compared with whites might then
      be consequent not only to a high dietary salt intake but also to a marginally
      reduced dietary potassium intake. Under controlled metabolic conditions, we
      compared acute vasopressor responses to cold and mental stress in black and white
      normotensive men during three successive dietary periods: (1) while dietary
      potassium was reduced (30 mmol K+/70 kg per day) and salt was restricted (10 to
      14 days); (2) while salt was loaded (15 to 250 mmol Na+/70 kg per day) (7 days);
      and (3) while salt loading was continued and potassium was either supplemented
      (70 mmol K+/70 kg per day) (7 to 21 days) in 9 blacks and 6 whites or continued
      reduced (30 mmol K+/70 kg per day) (28 days) in 4 blacks (time controls). At the
      lower potassium intake, cold-induced increase in forearm vascular resistance in
      blacks was twice that in whites during both salt restriction and salt loading.
      Normalization of dietary potassium attenuated cold-induced increases in both
      forearm vascular resistance and systolic and diastolic blood pressures in blacks
      but only in systolic pressure in whites. In blacks but not in whites,
      normalization of dietary potassium attenuated mental stress-induced increases in
      systolic and diastolic pressures. In normotensive blacks but not whites, a
      marginally reduced dietary intake of potassium reversibly enhances adrenergically
      mediated vasopressor responsiveness to stress. That responsiveness so enhanced
      over time might contribute to the pathogenesis of hypertension in blacks.

PMID- 9149671
TI  - Cancer risk in users of calcium channel blockers.
AB  - Ca2+ channel blockers may cause cancer by inhibiting apoptosis or reducing
      intracellular Ca2+ in certain tissues. Recent findings suggest that drug users
      are at increased risk for cancer in general and for colon cancer in particular.
      We conducted a study in one Danish county of 17911 patients who received at least
      one prescription of Ca2+ channel blockers between 1 January 1991 and 31 December
      1993. The patients were identified from records in the National Health Insurance
      Program, which refunds part of the price of such drugs. Cancer occurrence and
      rate were determined by use of the files of the Danish Cancer Registry and
      compared with county-specific incidence rates for various categories of cancer.
      During the follow-up period of up to 3 years, 412 cancers were observed among
      users of Ca2+ channel blockers, compared with 414 expected, to yield an age- and
      sex-standardized incidence ratio (SIR) of 1.00 (95% confidence interval, 0.90 to
      1.10). There was no indication of an excess risk in the subgroup of likely long
      term users or users of specific drugs. The SIR of colon cancer, a site of a
      priori interest, was 0.8 (95% confidence interval, 0.5 to 1.1) on the basis of 34
      cases. Although the results are reassuring, the lack of association could reflect
      the relatively short follow-up after registration in the prescription database.
      Continued monitoring of cancer risk is planned.

PMID- 9149672
TI  - Left ventricular mass in the elderly. The Cardiovascular Health Study.
AB  - Left ventricular (LV) mass, as estimated from M-mode echocardiography (echo), has
      previously been shown to be an independent predictor of incident cardiovascular
      disease morbidity and mortality. We evaluated the relationship at baseline of
      echo LV mass to relevant cardiovascular disease risk factors and other potential
      covariates in the Cardiovascular Health Study, multicenter study sponsored by the
      National Heart, Lung, and Blood Institute of 5201 men and women aged 65 years or
      older (mean, 73). Two-dimensionally directed M-mode echo LV mass measurements
      could be obtained in 1357 men and 2053 women (66% of this elderly cohort).
      Stepwise linear regression analyses of the relationship of echo LV mass to
      demographic and risk factor, physical activity, electrocardiographic, and
      prevalent disease variables resulted in a model that explained 37% of the
      variance for the entire cohort. In order of decreasing importance, factors
      positively associated with echo LV mass were body weight, male sex, systolic
      pressure, presence of congestive heart failure, present smoking, major and minor
      electrocardiographic abnormalities, treatment for hypertension, valvular heart
      disease, aortic regurgitation by color Doppler, and mitral regurgitation by color
      Doppler (in men) whereas diastolic pressure, bioresistance (a measure of
      adiposity), and high-density lipoprotein cholesterol were inversely related to
      echo LV mass. Although height and weight were both related to LV mass, height
      added nothing once weight was entered in multiple linear regression analyses.
      Furthermore, in the multiple regression models, diastolic pressure was inversely
      and systolic BP positively related to LV mass, with similar magnitudes for their
      coefficients. In consonance with these findings, pulse pressure was positively
      related to LV mass in bivariate analyses. Multiple linear regression analyses
      explained less of the variance for ventricular septal thickness (R2 = .13) and LV
      posterior wall thickness (R2 = .14) than for LV mass (R2 = .37) and LV diastolic
      dimension (R2 = .27). Intriguing findings in the elderly Cardiovascular Health
      Study cohort included the presence of pulse pressure as a positive correlate, and
      high-density lipoprotein cholesterol as an inverse correlate, of LV mass.
      Longitudinal studies in the Cardiovascular Health Study cohort will help to
      clarify the importance of demographic, risk factor, and other variables, and
      changes in these variables, in predicting changes in echo LV mass and its
      components as well as the prognostic significance of LV mass in the elderly.

PMID- 9149673
TI  - Distinct mechanisms of modulation of angiotensin II type I receptor gene
      expression in heart and aorta.
AB  - The purpose of the present study was to test the hypothesis that hypertension
      induced by reduced renal mass (RRM) upregulates gene expression of the type 1
      angiotensin II (Ang II) receptor (AT1) in the thoracic aorta and heart through an
      Ang II-dependent mechanism. Three groups of rats were given 1% NaCl water and
      subjected to RRM, RRM plus captopril (RRM+Cap, 30 mg/kg per day), or sham
      surgery. Tail-cuff systolic blood pressure was significantly elevated in RRM and
      RRM+Cap rats compared with sham-operated rats. The ratios of the medial wall area
      of the thoracic aorta and heart weight to body weight were significantly elevated
      in RRM and RRM+Cap rats compared with sham-operated rats. Northern blot analysis
      indicated that the ratio of AT1 to GAPDH mRNA in the aorta was significantly
      higher in RRM (1.85 +/- 0.52) compared with sham-operated (0.21 +/- 0.04) and
      RRM+Cap (0.55 +/- 0.20) rats. In contrast, the ratio of AT1 to GAPDH mRNA in the
      heart was significantly increased in both RRM (1.09 +/- 0.23) and RRM+Cap (1.00
      +/- 0.09) compared with sham-operated (0.34 +/- 0.06) rats. Thus, RRM
      hypertension upregulates AT1 mRNA expression in both the hypertrophied aorta and
      heart. Captopril treatment without altering blood pressure in RRM rats prevents
      the increase in AT1 mRNA in the aorta but not the heart. These results suggest
      that different tissue-specific mechanisms of AT1 gene regulation exist; ie, in
      aorta, an Ang II-or kinin-dependent mechanism is operant, whereas in heart, RRM
      induced upregulation of AT1 mRNA may be pressure dependent.

PMID- 9149674
TI  - Confirmation or exclusion of stage I hypertension by ambulatory blood pressure
      monitoring.
AB  - Criteria for the diagnosis or exclusion of hypertension using ambulatory blood
      pressure monitoring have not been agreed upon. We designed this study to provide
      a statistically based guide for using results of ambulatory blood pressure
      monitoring to resolve this issue. To generate this information, we used a
      database of 228 subjects (135 men, 93 women; average age, 45 years) referred by
      their primary physicians over the past 7 years for evaluation of borderline or
      stage I hypertension (average blood pressure, 148/92 mm Hg; SD, +/-17.5/12.2 mm
      Hg). In this population, the pooled SDs of systolic and diastolic ambulatory
      blood pressures were 13.8 and 11.6 mm Hg, respectively. Using the pooled SD, we
      calculated the probability that a patient's blood pressure falls within the
      hypertensive range (> 140/90 mm Hg). The 95% confidence interval for each
      subject's blood pressure was also determined. For example, if 40 ambulatory blood
      pressure measurements are performed on a subject and the average systolic
      ambulatory blood pressure is 137 mm Hg, then there is a 10% probability that the
      patient's "true" average blood pressure is actually in the hypertensive range. By
      contrast, if the systolic pressure is 143 mm Hg, there is a 90% probability that
      the patient is hypertensive. This approach may be useful for clinical decision
      making and also for the design of clinical trials.

PMID- 9149675
TI  - Neural circulatory responses to carbon monoxide in healthy humans.
AB  - The contribution of carbon monoxide (CO) to the acute cardiovascular effects of
      smoking is not clear. Using a double-blind, randomized, vehicle-controlled study
      design, we examined the sympathetic and vascular responses to modest increases in
      carboxyhemoglobin in 10 healthy humans. We measured muscle sympathetic nerve
      activity (microneurography), forearm blood flow (plethysmography), heart rate,
      blood pressure, and minute ventilation at baseline and during 60 minutes of CO
      inhalation (1000 ppm during the first 30 minutes and 100 ppm during the last 30
      minutes). The same measurements were made in a vehicle session (room air
      inhalation) on a separate day. During the first 30 minutes of CO inhalation,
      carboxyhemoglobin levels increased progressively from 0.2 +/- 0.1% to 8.3 +/-
      0.5% and were maintained at about this level for a further 30 minutes. Forearm
      vascular resistance did not change with CO but increased slightly with vehicle;
      the effects of CO on muscle sympathetic nerve activity, forearm blood flow, blood
      pressure, heart rate, and minute ventilation were not significantly different
      from the effects of vehicle. Modest increases in carboxyhemoglobin levels
      equivalent to those resulting from cigarette smoking are unlikely to contribute
      to the acute sympathetic and hemodynamic effects of smoking in healthy humans.

PMID- 9149676
TI  - Baroreflex sensitivity assessed by complex demodulation of cardiovascular
      variability.
AB  - We used complex demodulation of cardiac interval and systolic arterial blood
      pressure oscillations in the low-frequency band (0.04 to 0.14 Hz) to investigate
      baroreceptor control of heart rate. Baroreflex sensitivity was defined as the
      instantaneous amplitude of complex-demodulated oscillations in the RR interval
      divided by the instantaneous amplitude of complex-demodulated oscillations in
      systolic blood pressure. We evaluated the method using both simulated and actual
      data obtained from 33 healthy nonsmokers during supine and standing postures. To
      test the validity and reliability of the method, we compared the mean values of
      baroreflex sensitivity calculated using complex demodulation with the values
      obtained using power spectral analysis and sequential analysis of spontaneous
      variations in blood pressure and RR interval. All three methods applied to the
      simulated data yielded the same values of baroreceptor sensitivity. Mean values
      of baroreflex sensitivity assessed by complex demodulation of the actual data
      were similar to those calculated by both power spectral analysis and sequential
      analysis (13.9 +/- 5.2 versus 13.7 +/- 6.7 or 14.3 +/- 6.5 ms/mm Hg for supine
      and 7.3 +/- 2.8 versus 7.0 +/- 3.0 or 7.2 +/- 2.8 ms/mm Hg for standing,
      respectively). In addition, a significant correlation existed between the values
      obtained by complex demodulation and power spectral analysis (r = .97, P = .0001)
      and sequential analysis (r = .98, P = .0001). Furthermore, complex demodulation
      derived baroreflex sensitivity fluctuated across time during both the supine and
      standing postures, and this could not be discerned by power spectral analysis.
      The results indicate that complex demodulation provides a dynamic assessment of
      baroreflex sensitivity and may be a useful tool in exploring reflex autonomic
      control of the cardiovascular system.

PMID- 9149677
TI  - ANP enhances bradycardic reflexes in normotensive but not spontaneously
      hypertensive rats.
AB  - Baroreflex control of heart rate in spontaneously hypertensive rats (SHR) is
      defective, largely because of a poor vagal contribution to the reflex. We have
      demonstrated previously that atrial natriuretic peptide (ANP) enhances reflex
      bradycardia in normotensive rats through an action on nonarterial vagal afferent
      pathways. In the present study, we investigated whether ANP could reverse the
      baroreflex abnormality in SHR. Heart rate reflexes were activated by three
      different methods in conscious, instrumented SHR and Wistar-Kyoto rats (WKY) in
      the presence of intravenous infusions of vehicle (saline) or rat ANP (150 ng/kg
      per minute). Heart rate responses were measured by (1) the steady-state changes
      in blood pressure after alternating slow infusions (over approximately 15 to 30
      seconds) of a pressor (methoxamine) and depressor (nitroprusside) drug
      (stimulating predominantly arterial baroreceptors), (2) the ramp method of rapid
      infusion of methoxamine (over < 10 seconds; stimulating arterial and
      cardiopulmonary baroreceptors), and (3) the von Bezold-Jarisch method of
      activating chemically sensitive cardiac receptors through serotonin injections.
      ANP enhanced the heart rate range of the arterial baroreflex (steady-state
      method) by 13 +/- 3% in WKY but had no significant effect on the sensitivity or
      any other parameter of the steady-state baroreflex. When a very rapid rise in
      blood pressure was elicited by the ramp method in WKY, ANP significantly enhanced
      baroreflex bradycardia (sensitivity increased by 29 +/- 9%, P < .05). ANP also
      enhanced the bradycardia of the von Bezold-Jarisch reflex (by 33 +/- 16%, P <
      .05) in WKY. By contrast, ANP did not influence baroreceptor or chemoreceptor
      heart rate reflex responses in SHR. We conclude that in normotensive rats, ANP
      facilitates cardiopulmonary bradycardic reflexes. The lack of effect of ANP in
      SHR may be related to an underlying structural or genetic alteration in their
      cardiac sensors, perhaps associated with cardiac hypertrophy, that prevents the
      ANP-induced activation of cardiac sensory afferents, resulting in
      cardioinhibition.

PMID- 9149678
TI  - Tumor recurrence and hypertension persistence after successful pheochromocytoma
      operation.
AB  - Pheochromocytoma is a catecholamine-secreting tumor and a rare cause of
      hypertension that is usually curable. However, pheochromocytoma may recur as a
      benign or malignant tumor, and hypertension may persist after successful surgical
      intervention. The frequency of and risk indicators for tumor recurrence and
      hypertension persistence after successful surgical intervention have not been
      adequately studied. We determined tumoral and blood pressure outcome in 129
      patients followed-up from initial pheochromocytoma resection to death or to 1994
      (796 patient-years). We assessed several candidate indicators for their
      predictive value for the risk of tumor recurrence or hypertension persistence.
      Recurrence was defined as the reappearance of disease after normalization of
      biochemical tests. Pheochromocytoma caused death or persistent or recurrent
      disease in 28 patients. Of the 114 with benign tumors at initial operation,
      pheochromocytoma recurred as a benign or malignant tumor 17 to 194 months after
      initial operation in 16 cases. Kaplan-Meier estimates of pheochromocytoma-free
      survival were 92% and 80% at 5 and 10 years, respectively. In the 98 living
      patients without recurrence, Kaplan-Meier estimates of hypertension-free survival
      were 74% and 45% at 5 and 10 years. In the Cox model, familial pheochromocytoma
      and a low ratio of plasma epinephrine to total catecholamines were independently
      associated with recurrence. Familial hypertension and age were similarly
      associated with hypertension persistence. After surgery for pheochromocytoma,
      patients should be followed-up indefinitely, especially those with familial
      tumors or a low epinephrine secretion. Pheochromocytoma should not unreservedly
      be considered a surgically remediable cause of hypertension.

PMID- 9149679
TI  - Differential alteration in vascular structure of resistance arteries isolated
      from the cerebral and mesenteric vascular beds of transgenic [(mRen-2)27],
      hypertensive rats.
AB  - In this study we examined the structural properties of cerebral and mesenteric
      resistance arteries isolated from normotensive, Sprague-Dawley (SD) rats (mean
      arterial pressure [MAP], 110 +/- 3 mm Hg) and hypertensive, transgenic (TG) rats
      (MAP, 167 +/- 4 mm Hg), which express the mouse Ren-2 renin gene. Vessels were
      set up in a pressure myograph, and ID and vascular wall thickness were determined
      at increasing intraluminal pressures. Arteries were subsequently pressurized to
      the MAP of the animal from which they were isolated and were fixed with
      glutaraldehyde before being embedded in araldite, sectioned, and examined
      histologically. The middle cerebral artery (MCA) isolated from SD rats and TG
      rats had similar media cross-sectional areas. There was no difference in MCA
      diameter at 10 mm Hg in vessels from TG rats compared with SD rats. However, at
      higher distending pressures, the diameter of the MCA from TG rats was
      significantly smaller than that of vessels from SD rats. This reduced ID at the
      higher pressures was a consequence of a decreased distensibility of the MCA from
      TG rats (as shown by a leftward shift of the stress-strain relationship in
      arteries from TG rats) and was not caused by an increase in wall thickness. First
      and second-order mesenteric resistance arteries isolated from TG rats displayed
      an increased wall thickness and media content compared with vessels from SD rats.
      However, this alteration in mesenteric artery structure did not impinge on the ID
      of arteries from TG rats; there was no difference in the IDs of mesenteric
      resistance arteries between the two strains at any distending pressure. These
      observations show that there are distinct regional alterations in vascular
      structure in hypertensive TG rats expressing the mouse Ren-2 renin gene.
      Mesenteric resistance arteries isolated from TG rats display signs of vascular
      growth, although this structural alteration does not produce a reduction in the
      ID of these arteries per se. In contrast, cerebral arteries from TG rats do not
      show increased growth but have a reduced vascular distensibility, which results
      in a smaller ID compared with vessels from SD rats.

PMID- 9149680
TI  - Adrenomedullin stimulates renin release and renin mRNA in mouse juxtaglomerular
      granular cells.
AB  - The recently discovered peptide adrenomedullin (AM) alters blood pressure through
      effects on the resistance vessels. Moreover, AM modifies the secretion of
      corticotropin and aldosterone and could thereby indirectly influence blood
      pressure through the renin-angiotensin-aldosterone system. Although plasma AM and
      renin concentration have been found to directly correlate, a causal linkage
      between AM and renin has not been shown. The present study tested the influence
      of AM on renin secretion and renin gene expression by renal juxtaglomerular
      granular cells. Prominent expression and release of AM by vascular structures has
      been reported; therefore, we investigated the local expression of AM in
      juxtaglomerular structures. Renin release from isolated perfused rat kidneys was
      dose-dependently increased by AM (1 to 30 nmol/L), whereas renal perfusate flow
      rate increased up to 17% at a constant perfusion pressure of 100 mm Hg. In
      primary cultures of mouse granular cells, AM augmented renin release, renin mRNA
      accumulation, and cAMP production in a dose- and time-dependent manner (threshold
      values in the range 10 pmol/L to 1 nmol/L). By reverse transcription-polymerase
      chain reaction, significant expression of the AM gene was detected in
      microdissected rat glomeruli with afferent arterioles and in primary cultures of
      mesangial and granular cells. We conclude that AM is expressed in juxtaglomerular
      structures and that it has a direct stimulatory effect on renin secretion and
      renin mRNA abundance by receptors on juxtaglomerular cells, possibly through
      increases in cAMP. AM could act as an autocrine/paracrine stimulatory factor in
      the control of renin secretion and renin gene expression.

PMID- 9149681
TI  - Effect of mechanical loading on vascular alpha 1D- and alpha 1B-adrenergic
      receptor expression.
AB  - Heterogeneous distribution and function of alpha 1-adrenergic receptor subtypes
      on arterial and venous vessels, together with evidence for altered alpha
      adrenergic receptor expression in hypertension, led us to examine whether
      mechanical load influences expression of alpha 1B- and alpha 1D-adrenergic
      receptors in rat aortic smooth muscle cells (SMCs). We used RNase protection and
      radioligand binding assays to measure mRNA and alpha 1-adrenergic receptor
      density. In the first model, SMCs were subjected to phasic loading using flexible
      culture plates. As a positive control for the load stimulus, postconfluent,
      quiescent passage 5 cells demonstrated the expected load-dependent morphological
      realignment. However, no changes were detected in expression of either alpha 1D-
      or alpha 1B-adrenergic receptor mRNAs or receptor density after 24 to 48 hours of
      loading. beta-Actin and SMC-specific alpha-actin mRNA, as well as cell number and
      per-cell total RNA and protein, were also unaffected. In a second model, intact
      thoracic aortas, in either the presence or absence of endothelial cells, were
      cultured for 48 hours under tonic load. Like cultured cells, 48 hours of load did
      not affect SMC expression of alpha 1-adrenergic receptor mRNAs. We used
      suprarenal aortic coarctation to examine effects of increased pressure in vivo.
      As with the previous in vitro and in situ models, hypertension (30 days) had no
      effect on expression of alpha 1B- and alpha 1D-adrenergic receptor mRNAs in the
      suprarenal aorta compared with sham coarctation. To separate pressure per se from
      humoral influences, we also measured mRNAs in the subrenal, normotensive aorta,
      alpha 1B mRNA levels decreased to 68 +/- 14% of sham-coarcted controls in
      subrenal aorta exposed to normal blood pressure but also to systemic humoral
      changes induced by coarctation. As a positive control for a load effect, SMC
      specific alpha-actin mRNA increased for loaded aorta in organ culture and in
      hypertensive aorta in vivo, whereas expression of beta-actin mRNA was unaffected.
      These results from cell culture, organ culture, and in vivo models suggest that
      pressure (load) alone has no effect on alpha 1B- and alpha 1D-adrenergic receptor
      expression. In coarctation hypertension, smooth muscle protected from the
      hypertension showed a decline in alpha 1B mRNA that may be due to a humoral
      factor or factors.

PMID- 9149682
TI  - Mechanical load opposes angiotensin-mediated decrease in vascular alpha 1
      adrenoceptors.
AB  - alpha 1-Adrenergic receptor contraction of vascular smooth muscle is augmented by
      increases in angiotensin II and also in several forms of hypertension. Whether
      angiotensin directly modulates alpha 1-adrenoceptor subtype expression to
      contribute to this effect is unknown. In a previous study, we demonstrated that
      increased mechanical load (pressure) per se does not alter expression of alpha 1B
      and alpha 1D-adrenoceptors in rat aortic smooth muscle in cell culture, in vitro
      or in vivo. However, findings in aortic coarctation hypertension suggested that a
      humoral factor, possibly angiotensin, selectively reduces alpha 1B-adrenoceptors
      and that increased mechanical load opposes this decrease. The present study
      examined this hypothesis by determining the effect of angiotensin alone and in
      the presence of mechanical loading on the expression of alpha 1D- and alpha 1B
      adrenergic receptor mRNAs and alpha 1-receptor density in cultured aortic smooth
      muscle cells. alpha 1D mRNA content, per smooth muscle cell, concentration
      dependently decreased after 3 hours of exposure to 0.3 nmol/L to 1 mumol/L
      angiotensin but by 24 hours had returned to control levels. In contrast, alpha 1B
      mRNA concentration-dependently declined at a later time (24 hours) and remained
      decreased at 48 hours to 27 +/- 6% of control with 1 mumol/L angiotensin.
      Angiotensin also decreased alpha 1-adrenoceptor density in a dose-dependent
      manner. Angiotensin had no effect on cell number in these confluent, quiescent
      cells but did increase cell protein and total RNA. This cellular hypertrophy and
      the decreases in alpha 1-adrenoceptor mRNAs were blocked by the angiotensin type
      1 receptor antagonist losartan. Cyclic mechanical loading of smooth muscle cells
      opposed the angiotensin-mediated hypertrophy and decrease in alpha 1B mRNA
      expression and alpha 1-adrenergic receptor density. These data suggest that
      angiotensin and intravascular pressure interact to affect cell growth and
      expression of alpha 1B-adrenergic receptors by vascular smooth muscle.

PMID- 9149683
TI  - Metformin inhibits ganglionic neurotransmission in renal nerves.
AB  - Intravenous administration of the antihyperglycemic agent metformin decreases
      arterial pressure and sympathetic nerve activity (SNA). To test the hypothesis
      that metformin inhibits SNA by interrupting ganglionic neurotransmission, we
      compared the actions of intravenous administration of metformin and the
      ganglionic blocker trimethaphan on postganglionic renal and preganglionic adrenal
      sympathetic nerves in pentobarbital-anesthetized male Sprague-Dawley rats.
      Intravenous metformin elicited dose-dependent decreases in postganglionic renal
      SNA (1 mg/kg: 0 +/- 0%; 10 mg/kg: -20 +/- 4%; 100 mg/kg: -92 +/- 3%; n = 7).
      Conversely, only the maximal dose of metformin affected preganglionic adrenal SNA
      (100 mg/kg: delta adrenal SNA = -14 +/- 6%; n = 8). Ganglionic blockade with
      intravenous trimethaphan (5 mg/kg) produced a differential sympathoinhibitory
      response similar to the response observed after high-dose metformin (delta renal
      SNA = -100 +/- 3%; delta adrenal SNA = -17 +/- 7%; P < .001). Preganglionic renal
      neurons were electrically stimulated in the spinal cord, before and during the
      peak of the sympathoinhibitory response to intravenous metformin, and the
      magnitude of the stimulus-evoked increases in postganglionic renal SNA were
      compared. Metformin dose-dependently attenuated the magnitude of the increase in
      postganglionic renal SNA elicited by stimulation of the spinal cord (30 mg/kg: 
      23 +/- 8%; 90 mg/kg: -65 +/- 11%; 270 mg/kg: -91 +/- 8%; n = 6 per dose). We
      conclude that high-dose intravenous metformin interrupts ganglionic
      neurotransmission in renal nerves.

PMID- 9149684
TI  - Endothelin-1 upregulation in the kidney of uninephrectomized spontaneously
      hypertensive rats and its modification by the angiotensin-converting enzyme
      inhibitor quinapril.
AB  - Endothelin (ET-1) is a potent vasoconstrictor that plays an important role in the
      control of renal circulation and tubular function. The contribution of this
      peptide to the pathogenesis of systemic hypertension and renal failure remains
      largely undefined. In spontaneously hypertensive rats (SHR) uninephrectomized at
      20 weeks of age (UNX-SHR) and followed until 45 weeks of age, we determined ET-1
      gene expression in renal tissue by reverse transcription-polymerase chain
      reaction and its localization by in situ hybridization in paraffin-embedded
      kidney sections. Age-matched SHR and normotensive Wistar-Kyoto (WKY) rats were
      chosen as controls. At the end of the follow-up, UNX-SHR had high systolic blood
      pressure, intense proteinuria, mesangial expansion, focal and segmental
      glomerular sclerosis, and tubulointerstitial lesions. In relation to WKY and SHR,
      UNX-SHR exhibited an increase in ET-1 gene expression in renal cortex and
      medulla. By in situ hybridization and immunoperoxidase staining, an
      overexpression of ET-1 gene and protein were seen in mesangial and glomerular
      epithelial cells and in some proximal tubules and vessels. Angiotensin-converting
      enzyme (ACE) activity was significantly increased in the renal brush border.
      Since in mesangial cells, angiotensin II induces ET-1 synthesis, a group of UNX
      SHR received the ACE inhibitor quinapril from the time of UNX. These animals had
      a decrease in blood pressure, proteinuria, and serum and brush border ACE
      activity and in the expression and synthesis of ET-1 in all renal areas. On the
      whole, these data show that UNX-SHR have an upregulation of ET-1 gene and protein
      in several structures of the kidney compared with SHR and WKY rats. Quinapril
      diminished ACE activity and ET-1 expression and synthesis coincidentally with an
      improvement in proteinuria and morphological lesions. The beneficial effects of
      ACE inhibitors may be due to the diminution of both angiotensin II and ET-1
      generation.

PMID- 9149685
TI  - Chronic dietary L-arginine prevents endothelial dysfunction secondary to
      environmental tobacco smoke in normocholesterolemic rabbits.
AB  - Our goal was to determine whether environmental tobacco smoke causes endothelial
      dysfunction in the absence of hypercholesterolemia and whether such an effect can
      be prevented by supplementation with L-arginine. Environmental tobacco smoke
      exposure is associated with an increase in coronary artery disease events and
      mortality. We have previously demonstrated that environmental tobacco smoke
      causes endothelial dysfunction and atherosclerosis in rabbits with diet-induced
      hypercholesterolemia and atherosclerosis and that chronic dietary L-arginine
      supplementation prevents this. The effects of L-arginine supplementation (2.25%
      solution ad libitum) and environmental tobacco smoke (smoking chambers for 10
      weeks) were examined with a 2 x 2 design in 32 rabbits fed a normal diet.
      Acetylcholine, calcium ionophore A23187, and nitroglycerin-induced vasorelaxation
      were assessed in aortic rings precontracted with phenylephrine. Endothelial L
      arginine levels were measured by chromatography. Chronic L-arginine
      supplementation increased serum (P < .001) and endothelial (P = .003) L-arginine
      levels. Environmental tobacco smoke reduced endothelium-dependent acetylcholine
      induced relaxation, and L-arginine blocked this adverse effect (P = .04).
      Environmental tobacco smoke tended to increase phenylephrine-induced contraction
      (P = .06). Neither environmental tobacco smoke nor L-arginine influenced A23187
      induced relaxation nor endothelium-independent nitroglycerin-induced relaxation.
      Endothelial dysfunction secondary to environmental tobacco smoke may occur in the
      absence of diet-induced hypercholesterolemia and atherosclerosis. Chronic dietary
      supplementation with a nitric oxide donor such as L-arginine offsets the
      endothelial dysfunction associated with environmental tobacco smoke in
      normocholesterolemic rabbits, possibly through substrate loading of the nitric
      oxide pathway.

PMID- 9149686
TI  - Nifedipine attenuates systemic and renal vasoconstriction during nitric oxide
      inhibition in humans.
AB  - Clinical states associated with nitric oxide deficiency are often accompanied by
      vasoconstriction. We studied the effects of prolonged infusion of the nitric
      oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) on systemic and renal
      hemodynamics in humans and the reversibility of the established vasoconstriction
      by calcium channel blockade with nifedipine. Seven healthy men underwent three 7
      hour clearance studies. During one study, L-NMMA (3 mg/kg priming dose plus 3
      mg.kg-1.h-1) was infused during hours 2 through 5, and during another study,
      nifedipine (0.015 mg/kg priming dose plus 0.015 mg.kg-1.h-1) was coinfused during
      hours 4 and 5. A third study served as time control. L-NMMA elicited reproducible
      systemic and renal vasoconstriction that was stable during the 4 hours of
      infusion. Systemic vascular resistance index, calculated from bioimpedance
      derived cardiac index, increased from 22 +/- 1 to 29 +/- 2 mm Hg.min.m2.L-1 (P <
      .05). Mean arterial pressure rose by 4 +/- 1 mm Hg (P < .05), and heart rate,
      stroke index, and cardiac index decreased. Renal blood flow, calculated from
      renal plasma flow, decreased from 1182 +/- 101 to 785 +/- 53 mL/min, and renal
      vascular resistance increased from 73 +/- 5 to 115 +/- 6 mm Hg.min.L-1 (P < .05).
      Glomerular filtration rate decreased from 114 +/- 6 to 104 +/- 6 mL/min (P <
      .05), and filtration fraction increased. Sodium excretion fell from 89 +/- 9 to
      32 +/- 7 mumol/min (P < .05). Nifedipine completely reversed systemic
      vasoconstriction. Nifedipine caused partial restoration of renal vascular
      resistance and complete normalization of glomerular filtration rate and sodium
      excretion but left the elevated filtration fraction unaltered. We conclude that
      sustained nitric oxide deficiency in humans is accompanied by strong systemic and
      renal vasoconstriction, decreased glomerular filtration rate, and sodium
      retention. Nifedipine can reverse most of these effects, suggesting a role for
      calcium channel blockade in pathological states of impaired nitric oxide
      activity.

PMID- 9149687
TI  - Time course changes of the mechanical properties of the carotid artery in renal
      hypertensive rats.
AB  - Distensibility of the carotid artery is not altered 2 weeks after renal artery
      clipping despite adaptive vascular hypertrophy related to hypertension. The
      purpose of this study was to assess arterial wall behavior with hypertension
      persisting for a longer period. Male Wistar rats were examined 1, 5, 9, and 24
      weeks after renal artery clipping (two-kidney, one clip renal hypertension; n =
      40) or after sham operation (n = 39). Mean blood pressure increased significantly
      to 132 +/- 4, 143 +/- 4, 153 +/- 4, and 144 +/- 4 versus 98 +/- 2, 107 +/- 2, 115
      +/- 3, and 108 +/- 3 mm Hg, respectively, in 1-, 5-, 9-, and 24-week hypertensive
      rats and age-matched controls. Cardiac and vascular hypertrophy increased in
      parallel and were correlated to mean blood pressure. Wall stress at mean blood
      pressure did not differ between the hypertensive and normotensive groups (3.79 +/
      0.24, 4.60 +/- 0.34, 4.49 +/- 0.27, and 4.14 +/- 0.28 versus 3.15 +/- 0.12, 4.14
      +/- 0.25, 4.80 +/- 0.28, and 4.69 +/- 0.32 10(3) dyne/cm2, respectively, in 1-, 5
      , 9-, and 24-week hypertensive rats and age-matched controls). Distensibility
      pressure data from the two groups fell on a common curve for all study periods.
      The intrinsic properties of the wall constituents were similar in controls and
      hypertensive rats at 1 and 5 weeks. However, the arteries became stiffer in the 9
      and 24-week hypertensive rats, as illustrated by a shift to higher levels of the
      incremental elastic modulus-stress curve. Wall stress remains constant at mean
      blood pressure as a result of the increase in wall tissue mass. With time, even
      though the distensibility-pressure curve is not shifted downward, the thickened
      wall becomes stiffer in the hypertensive rats, which may predispose them to
      accelerated alterations of the wall material.

PMID- 9149688
TI  - Cardiovascular effects of anandamide in anesthetized and conscious normotensive
      and hypertensive rats.
AB  - We previously showed that in anesthetized rats anandamide elicits bradycardia and
      a triphasic blood pressure response: transient hypotension secondary to a vagally
      mediated bradycardia, followed by a brief pressor and prolonged depressor
      response, the latter two effects being similar to those of delta 9
      tetrahydrocannabinol (THC). The prolonged depressor but not the pressor response
      was reduced after alpha-adrenergic receptor blockade or cervical spinal cord
      transection and was inhibited by the cannabinoid type 1 (CB1) receptor antagonist
      SR141716A, suggesting CB1 receptor-mediated sympathoinhibition as the underlying
      mechanism. Here we examined the relationship between sympathetic tone and the
      cardiovascular effects of anandamide by testing these effects in both conscious
      and anesthetized, normotensive and spontaneously hypertensive rats. In urethane
      anesthetized normotensive rats, SR141716A inhibited the prolonged depressor and
      bradycardic effects of anandamide and THC with similar potency, whereas it did
      not affect the pressor response to either agent. Anadamide caused similar
      hypotension in spontaneously breathing and in paralyzed, mechanically ventilated
      rats, suggesting that the hypotension is not secondary to respiratory effects. In
      conscious normotensive rats, anandamide elicited transient vagal activation and a
      brief pressor response, but the prolonged hypotensive component was absent.
      SR141716A potentiated and prolonged the brief pressor response to anandamide,
      suggesting that the depressor response may have been masked by an increased
      pressor response. All three phases of the anadamide response were present in both
      anesthetized and conscious spontaneously hypertensive rats, and the hypotensive
      component, inhibited by SR141716A in both, was more prolonged in the absence (>
      50 minutes) than the presence (10 to 15 minutes) of anesthesia. We conclude that
      anandamide causes a non-CB1 receptor-mediated pressor and a CB1 receptor-mediated
      prolonged depressor response. The depressor response can be elicited in both
      conscious and anesthetized animals, but its magnitude depends on preexisting
      sympathetic tone.

PMID- 9149689
TI  - Imperfect plans for health research in Europe.

PMID- 9149690
TI  - Microchimerism and graft tolerance: cause or effect?

PMID- 9149691
TI  - Mind over matter about keeping warm.

PMID- 9149692
TI  - Private genes, public health.

PMID- 9149693
TI  - Hepatitis B and health-care workers.

PMID- 9149694
TI  - Reducing the burden of mental illness.

PMID- 9149695
TI  - Cold exposure and winter mortality from ischaemic heart disease, cerebrovascular
      disease, respiratory disease, and all causes in warm and cold regions of Europe.
      The Eurowinter Group.
AB  - BACKGROUND: Differences in baseline mortality, age structure, and influenza
      epidemics confound comparisons of cold-related increases in mortality between
      regions with different climates. The Eurowinter study aimed to assess whether
      increases in mortality per 1 degree C fall in temperature differ in various
      European regions and to relate any differences to usual winter climate and
      measures to protect against cold. METHODS: Percentage increases in deaths per day
      per 1 degree C fall in temperature below 18 degrees C (indices of cold-related
      mortality) were estimated by generalised linear modelling. We assessed protective
      factors by surveys and adjusted by regression to 7 degrees C outdoor temperature.
      Cause-specific data gathered from 1988 to 1992 were analysed by multiple
      regression for men and women aged 50-59 and 65-74 in north Finland, south
      Finland, Baden-Wurttemburg, the Netherlands, London, and north Italy (24 groups).
      We used a similar method to analyse 1992 data in Athens and Palermo. FINDINGS:
      The percentage increases in all-cause mortality per 1 degree C fall in
      temperature below 18 degrees C were greater in warmer regions than in colder
      regions (eg, Athens 2.15% [95% CI 1.20-3.10] vs south Finland 0.27% [0.15-0.40]).
      At an outdoor temperature of 7 degrees C, the mean living-room temperature was
      19.2 degrees C in Athens and 21.7 degrees C in south Finland; 13% and 72% of
      people in these regions, respectively, wore hats when outdoors at 7 degrees C.
      Multiple regression analyses (with allowance for sex and age, in the six regions
      with full data) showed that high indices of cold-related mortality were
      associated with high mean winter temperatures, low living-room temperatures,
      limited bedroom heating, low proportions of people wearing hats, gloves, and
      anoraks, and inactivity and shivering when outdoors at 7 degrees C (p < 0.01 for
      all-cause mortality and respiratory mortality; p > 0.05 for mortality from
      ischaemic heart disease and cerebrovascular disease). INTERPRETATION: Mortality
      increased to a greater extent with given fall of temperature in regions with warm
      winters, in populations with cooler homes, and among people who wore fewer
      clothes and were less active outdoors.

PMID- 9149696
TI  - Regional patterns of disability-free life expectancy and disability-adjusted life
      expectancy: global Burden of Disease Study.
AB  - BACKGROUND: Information on non-fatal health outcomes of disease and injury has
      been largely neglected in health planning because of the conceptual and
      definitional complexity of measuring morbidity and disability in populations. One
      of our major objectives was to quantify disability for inclusion in health policy
      debates. We analysed these health outcomes in terms of disability-free life
      expectancy (DFLE) and disability-adjusted life expectancy (DALE). METHODS:
      Published and unpublished data were systematically reviewed to estimate the
      incidence, prevalence, and duration of 483 disabling sequelae of 107 diseases and
      injuries. To ensure internal consistency of these estimates, a software programme
      (DISMOD) was applied many times until consistent parameters were identified. The
      severity of disability, on a scale of 0 (perfect health) to 1 (death), was
      measured in a deliberate manner by the person-trade-off method. Spearman's and
      Pearson's correlation coefficients were used to measure disability weights among
      groups. Prevalence of seven classes of disability was back-calculated from the
      distribution of each disabling sequela across disabilities. Prevalence for each
      class of disability for different age-sex groups was used to calculate seven
      forms of DFLE and DALE based on Sullivan's method. FINDINGS: Prevalence of most
      disability classes is highest in sub-Saharan Africa and lowest in established
      market economies. Low-severity disabilities (class I and class II) are the most
      common. The expectation at birth of class I disability ranges from 6.5 years in
      established market economies to 14.7 years in sub-Saharan Africa, and for class
      II disabilities, from 8.5-18.4 years. DFLE varies significantly among regions:
      DFLE for class I disabilities at birth ranges from 9.9 years in sub-Saharan
      Africa to 47.7 years in established market economies for females and DFLE for
      class V disabilities ranges from 43.4 years for men in sub-Saharan Africa to 74.8
      years for women in established market economies. The proportion of expected life
      span at birth lived with disability adjusted for severity, varies from about 8%
      in established market economies to 15% in sub-Saharan Africa, with little
      difference between men and women. In high-income regions, nearly 90% of expected
      disability is due to non-communicable diseases and most of the remainder to
      injuries. In poorer regions, almost half of expected disability is due to
      communicable diseases and injuries. INTERPRETATION: The higher proportion of
      lifespan spent disabled in high-mortality populations is consistent with the
      compression of morbidity hypothesis. The threshold definition of disability used
      substantially affects the results of DFLE, DALE, which incorporates severity
      weights for disabilities, is a useful summary measure of the burden of disability
      and mortality.

PMID- 9149697
TI  - Polymorphisms of alpha-adducin and salt sensitivity in patients with essential
      hypertension.
AB  - BACKGROUND: Abnormalities in renal sodium transport may be involved in
      hypertension. Adducin, an alpha/beta heterodimeric protein found in the renal
      tubule is thought to regulate ion transport through changes in the actin
      cytoskeleton. We investigated whether an alpha-adducin polymorphism (Gly 460 Trp)
      is involved in essential hypertension in two separate populations. METHODS:
      Linkage analysis of three DNA markers at different distances from the alpha
      adducin locus (20-2500 kb) was done in 137 hypertensive sibling-pairs. 477
      hypertensive and 322 normotensive individuals were genotyped for the alpha
      adducin polymorphism. The blood-pressure response to acute and chronic changes in
      sodium balance was studied in hypertensive individuals with and without the 460
      Trp alpha-adducin allele. FINDINGS: Significant linkage was found for all three
      markers in the sibling-pair study. The extra shared alleles (9.1%, 6.5%, and
      4.7%) and the significance level for linkage (p = 0.0006, p = 0.0119, and p =
      0.0211) both decreased with increasing distance from the alpha-adducin locus.
      There was a significant association between the 460 Trp mutation and hypertension
      (p = 0.0003). In the salt-sensitivity test, to assess the acute blood-pressure
      response to changes in body sodium in 86 hypertensive patients, the decrease in
      mean arterial pressure was greater in 65 patients who were heterozygous for the
      mutant allele (Gly/Trp) than in 21 wild-type homozygotes (Gly/Gly) (mean decrease
      15.9 [SE 2.0] vs 7.4 [1.3] mm Hg; p = 0.001). Similarly, 21 heterozygous
      hypertensive patients showed a greater fall in mean arterial pressure in response
      to 2 months' treatment with hydrochlorothiazide than did 37 wild-type homozygous
      hypertensive patients (mean decrease 14.7 [2.2] vs 6.8 [1.4] mm Hg; p = 0.002).
      INTERPRETATION: Our findings of significant linkage of the alpha-adducin locus to
      essential hypertension and greater sensitivity to changes in sodium balance among
      patients with the mutant allele suggest that alpha-adducin is associated with a
      salt-sensitive form of essential hypertension. We suggest the alpha-adducin
      polymorphism may identify hypertensive patients who will benefit from diuretic
      treatment or manoeuvres to reduce total body sodium.

PMID- 9149698
TI  - Microchimerism and rejection in clinical transplantation.
AB  - BACKGROUND: Haemopoietic microchimerism has been identified in recipients of
      solid-organ transplants and is thought by some to be critical for the development
      and maintenance of immunological tolerance. The aim of this study was to
      correlate prospectively the persistence of donor cells with clinical outcome in
      recipients of kidney, kidney and pancreas, and liver transplants. METHODS:
      Persistence of donor cells in recipient peripheral blood was assessed at 3 days,
      and at 1, 3, 6, and 12 months after transplantation by a two-stage nested PCR
      technique to detect donor MHC HLA DR gene specifically. A pretransplant blood
      sample was collected from each patient to serve as an individual negative
      control. Seven liver, six kidney and pancreas, and 17 kidney patients were
      enrolled. 12 of the 17 kidney patients and all of the kidney and pancreas, and
      liver recipients were suitable for analysis. Exact matches for donors and
      recipients at the HLA DR loci (n = 1) or inability to obain primer pair
      specificity among similar HLA DR types (n = 4), meant that we were unable to
      analyse five patients. FINDINGS: Donor DNA was detected in 20 (80%) of 25, ten
      (40%) of 25, seven (30%) of 23, five (22%) of 23, and six (32%) of 19 recipients
      at 3 days, and 1, 3, 6 and 12 months post-transplant, respectively. Within
      individuals, the detection of donor DNA varied over time; only two patients had
      detectable donor DNA at all times. Analysis of the whole group of transplant
      patients showed a similar frequency and severity of rejection episodes in
      patients with and without microchimerism as defined by detectable donor DR genes.
      INTERPRETATION: These data suggest that a significant percentage of the
      recipients had persistent donor class II DNA in the peripheral circulation for at
      least 1 year after transplantation. We showed that a pretransplant blood sample
      is critical to avoid a false-positive result, and suggest that detectable
      chimerism may vary over time in individual patients. Therefore, analysis of
      microchimerism with a single, post-transplant analysis may not help in making
      clinical decisions for individual patients.

PMID- 9149699
TI  - An early marker for neurological deficits after perinatal brain lesions.
AB  - BACKGROUND: In normal awake infants, fidgety movements are seen from the age of 6
      weeks to 20 weeks. The aim of the study was to test the predictive value of
      absent or abnormal spontaneous movements in young infants for the later
      development of neurological deficits. METHODS: In a collaborative study involving
      five hospitals we collected data on the normal and abnormal quality of fidgety
      movements of 130 infants and compared it with assessments of neurological
      development done longitudinally until the age of 2 years. On the basis of
      ultrasound scans infants were classified as at low-risk or at high-risk of
      neurological deficits. Infants were videoed for 1 h every week from birth to
      discharge and then for 15 min every 3 to 4 weeks; quality of general movements
      was assessed. Repeated neurological assessments were also done until 24 months of
      corrected age. FINDINGS: 67 (96%) of 70 infants with normal fidgety movements had
      a normal neurological outcome. Abnormal quality or total absence of fidgety
      movements was followed by neurological abnormalities in 57 (95%) of the 60
      infants (49 had cerebral palsy and eight had developmental retardation or minor
      neurological signs). Specificity and sensitivity of fidgety movement assessment
      were higher (96% and 95%, respectively) than of ultrasound imaging of the
      infants' brain (83% and 80%, respectively). INTERPRETATION: Our technique of
      assessing spontaneous motor activity can identify and distinguish between those
      infants who require early intervention for neurological abnormalities and those
      who do not. Our technique is simple, non-intrusive, reliable, quick, and can be
      done on very young infants.

PMID- 9149700
TI  - Ecchymoses and eschars at sites of injection.

PMID- 9149701
TI  - Orally active prostacyclin analogue in primary pulmonary hypertension.

PMID- 9149702
TI  - Efficacy of camptothecin in progressive multifocal leucoencephalopathy.

PMID- 9149703
TI  - Bone-marrow transplantation in aspartylglucosaminuria.

PMID- 9149704
TI  - Human herpesvirus 7 in pityriasis rosea.

PMID- 9149706
TI  - High incidence of meningioma in survivors of Hiroshima.

PMID- 9149707
TI  - Dobrava hantavirus in Estonia: does the virus exist throughout Europe?

PMID- 9149705
TI  - Antibodies to human herpesvirus 8 in women and infants born in Haiti and the USA.

PMID- 9149708
TI  - Trypanosoma cruzi DNA in human mummies.

PMID- 9149709
TI  - Never say never to a cure for HIV-1 infection.

PMID- 9149710
TI  - Patterns of AIDS-related malignancies discussed at US meeting.

PMID- 9149711
TI  - South Africa revolutionises HIV prevention and education strategies.

PMID- 9149712
TI  - Mastocytosis.

PMID- 9149713
TI  - Occupational reproductive hazards.
AB  - Although the causes of many reproductive disorders remain unknown, scientific
      evidence is accumulating to implicate occupational agents in fertility disorders
      and adverse pregnancy outcomes. Effective assessment and management of workers
      exposed to reproductive hazards often involves a team-based approach. By
      identifying potential reproductive hazards, making appropriate referrals, and by
      educating and advocating for patients, clinicians can play an important part in
      safeguarding the reproductive health of workers.

PMID- 9149714
TI  - Neocytolysis: physiological down-regulator of red-cell mass.
AB  - It is usually considered that red-cell mass is controlled by erythropoietin
      driven bone marrow red-cell production, and no physiological mechanisms can
      shorten survival of circulating red cells. In adapting to acute plethora in
      microgravity, astronauts' red-cell mass falls too rapidly to be explained by
      diminished red-cell production. Ferrokinetics show no early decline in
      erythropolesis, but red cells radiolabelled 12 days before launch survive
      normally. Selective destruction of the youngest circulating red cells-a process
      we call neocytolysis-is the only plausible explanation. A fall in erythropoietin
      below a threshold is likely to initiate neocytolysis, probably by influencing
      surface-adhesion molecules. Recognition of neocytolysis will require re
      examination of the pathophysiology and treatment of several blood disorders,
      including the anaemia of renal disease.

PMID- 9149715
TI  - Infection, inflammation, and infarction: does acute endothelial dysfunction
      provide a link?

PMID- 9149717
TI  - Literature and history in medicine.

PMID- 9149716
TI  - Literature and history in medicine.

PMID- 9149718
TI  - Literature and history in medicine.

PMID- 9149719
TI  - Literature and history in medicine.

PMID- 9149721
TI  - HIV-prevention strategies.

PMID- 9149722
TI  - HIV-prevention strategies.

PMID- 9149723
TI  - Chorionic villus sampling and early amniocentesis for prenatal diagnosis.

PMID- 9149724
TI  - Chorionic villus sampling and early amniocentesis for prenatal diagnosis.

PMID- 9149725
TI  - ECMO for refractory cardiorespiratory failure due to meningococcal disease.

PMID- 9149726
TI  - ECMO for refractory cardiorespiratory failure due to meningococcal disease.

PMID- 9149727
TI  - Twinning rates.

PMID- 9149728
TI  - Aristolochia sp and chronic interstitial nephropathies in Indians.

PMID- 9149729
TI  - Directly observed therapy.

PMID- 9149730
TI  - PCR analysis of Y-chromosome deletions in subfertile men.

PMID- 9149731
TI  - Calcium-channel blockers and risk of cancer.

PMID- 9149732
TI  - Ethics of cloning.

PMID- 9149733
TI  - Ethics of cloning.

PMID- 9149734
TI  - Home-use HIV test kits in Turkey.

PMID- 9149735
TI  - Reproductive counselling for HIV-discordant couples.

PMID- 9149736
TI  - Packaging of nitric oxide.

PMID- 9149737
TI  - Biology and genetics of human neuroblastomas.
AB  - PURPOSE: Neuroblastomas have a variety of clinical behaviors, from spontaneous
      regression or differentiation to early metastasis and death. We have examined a
      variety of genetic variables that might explain or predict the clinical behavior.
      PATIENTS AND METHODS: We have studied DNA or RNA from a number of children
      enrolled in clinical trials with the major pediatric oncology cooperative groups.
      RESULTS: We propose that neuroblastomas may be classified into three subsets with
      distinct biological features and clinical behavior. The first subset consists of
      those tumors with hyperdiploid modal karyotypes and high TRK-A expression.
      Patients with these tumors are usually infants with low stages of disease and a
      very favorable outcome. The second group consists of tumors that have a near
      diploid DNA content, usually with 1p allelic loss or other structural changes,
      but they lack MYCN amplification, and TRK-A expression is low. The patients are
      generally older, with advanced stages of disease and an intermediate outcome. The
      third group is characterized by tumors with MYCN amplification, 1p allelic loss,
      and low or absent TRK-A expression. The patients are 1-5 years of age and have
      advanced stages of disease, rapid tumor progression, and a very poor prognosis.
      Current evidence suggests the tumor types are genetically distinct, and one type
      seldom if ever evolves into another. CONCLUSIONS: Identification of these genetic
      and clinical subsets permits a more accurate prediction of outcome. This, in
      turn, allows more appropriate selection of therapeutic intensity to minimize side
      effects in those with a favorable outcome but optimize the chance of cure in
      those requiring aggressive treatment.

PMID- 9149738
TI  - Impact of morning versus evening schedule for oral methotrexate and 6
      mercaptopurine on relapse risk for children with acute lymphoblastic leukemia.
      Nordic Society for Pediatric Hematology and Oncology (NOPHO).
AB  - PURPOSE: To study the risk of non-B-cell acute lymphoblastic leukemia (ALL)
      relapse in relation to the routines of administration of oral methotrexate (MTX)
      and 6-mercaptopurine (6MP) and to the erythrocyte (E) levels of the intracellular
      cytotoxic metabolites, that is, MTX polyglutamates and 6-thioguanine nucleotides
      (E-MTX and E-6TGN). PATIENTS AND METHODS: E-MTX and E-6TGN levels were measured
      at least three times (medians, eight and nine) in 294 children with non-B-cell
      ALL during oral MTX and 6MP therapy. For each patient, we registered (a) the
      individual circadian schedule of drug administration and (b) the coadministration
      of food, and (c) calculated a mean (m) of all E-MTX and E-6TGN measurements and
      (d) the product of mE-MTX and mE-6TGN (mE-MTX*6TGN), due to their synergistic
      action. RESULTS: A total of 42 patients were on a morning schedule, 219 were on
      an evening schedule, and 33 had miscellaneous routines. A total of 149 patients
      took the drugs with meals, 106 took the drugs between meals, and 39 had varying
      routines. With a median follow-up of 78 months, ALL has recurred in 66 patients.
      The patients on an evening schedule had a superior outcome [probability of event
      free survival (pEFS) = 0.82 +/- 0.03 vs. 0.57 +/- 0.08; p = 0.0002], whereas the
      coadministration of food did not significantly influence outcome. Patients with a
      mE-MTX*6TGN < 813 [product of median mE-MTX (4.7 nmol/mmol Hb) and mE-6TGN (173
      nmol/mmol Hb)] had an inferior outcome (pEFS = 0.70 +/- 0.04 vs. 0.85 +/- 0.03; p
      = 0.003), even if only patients on an evening schedule were analyzed. Thus, 109
      patients on the MTX/6MP evening schedule with an mE-MTX*6TGN < or = 813
      (nmol/mmol Hb)2 had a pEFS of 0.89 +/- 0.03 and a probability of continuous
      hematopoietic remission of 0.91 +/- 0.03. CONCLUSIONS: An evening schedule should
      be recommended for oral MTX/6MP maintenance therapy. The value of individual dose
      adjustments by E-MTX and E-6TGN remains to be determined in prospective
      randomized trials.

PMID- 9149739
TI  - One course versus two courses of antithymocyte globulin for the treatment of
      severe aplastic anemia in children.
AB  - PURPOSE: The aim of the therapeutic trials was to optimize the treatment of
      severe aplastic anemia (SAA) and moderate aplastic anemia in children who lack a
      suitable bone marrow donor, using immunosuppressive therapy in the most effective
      combination and dose. PATIENTS AND METHODS: Two sequential therapeutic trials for
      the treatment of severe and moderate aplastic anemia in children were conducted
      by 10 institutions. The treatment protocols included antithymocyte globulin
      (ATG), prednisone, and cyclosporine A (CSA); patients entered on the first
      protocol, 0190 (ATG X 2), were given two courses of ATG, and those enrolled on
      the second protocol, 0190B (ATG X 1), were given only one course of ATG. Ten
      patients were evaluable on ATG X 2. All patients had SAA; three had hepatitis
      induced severe aplastic anemia (HI-SAA). Twelve patients were evaluable on ATG X
      1; all had SAA, one of whom had HI-SAA. RESULTS: Seven of 10 patients on ATG X 2
      responded, and eight of 12 patients treated on ATG X 1 responded. CONCLUSION:
      Treatment with immunosuppressive therapy using ATG, CSA, and prednisone was very
      well tolerated. The response rates in both protocols were similar, and results
      compare favorably with those of previous therapeutic trials, suggesting that a
      second course of ATG is not necessary.

PMID- 9149740
TI  - Immunosuppressive therapy: a potential alternative to bone marrow transplantation
      as initial therapy for acquired severe aplastic anemia in childhood?
AB  - PURPOSE: Currently bone marrow transplantation (BMT) with an HLA-identical
      sibling donor is recommended as optimal therapy for children with acquired severe
      aplastic anemia (SAA). Immunosuppressive therapy (IST) has become a very
      successful initial therapy for SAA in children lacking a related bone marrow
      donor. We wished to evaluate whether current IST regimens may be as efficacious
      as BMT. PATIENTS AND METHODS: A retrospective review identified children treated
      for SAA over a 12-year period. Children with a related donor received a BMT.
      Children lacking a donor were treated with IST followed by a "rescue" BMT if IST
      was ineffective. IST consisted of anti-thymocyte globulin and steroid +/-
      cyclosporine A. Transfusion independence and survival rates were compared between
      the two groups. RESULTS: Twenty-seven children were identified. Nine received a
      related BMT; seven of these survive and are transfusion independent (median
      follow-up 54 months). Sixteen of 18 patients who received IST are transfusion
      independent survivors, including three of four patients who received a rescue BMT
      (median follow-up 33.5 months). Actuarial survival is 75% (95% CI = 45%, 105%)
      and 92% (95% CI = 78%, 107%) for the BMT and IST groups, respectively (p = 0.15).
      Severe toxicity was not experienced by any patient as a result of IST.
      CONCLUSIONS: Equivalent rates of transfusion independence and survival were
      experienced by patients receiving BMT and IST. We propose that a prospective
      trial be undertaken to evaluate IST as initial therapy in all children with SAA,
      to be followed by BMT if there is inadequate response.

PMID- 9149741
TI  - A feasibility, toxicity, and early response study of etoposide, ifosfamide, and
      vincristine for the treatment of children with rhabdomyosarcoma: a report from
      the Intergroup Rhabdomyosarcoma Study (IRS) IV pilot study.
AB  - PURPOSE: The purpose of this study was to determine the feasibility, toxicity,
      and early response of patients with clinical group III rhabdomyosarcoma (RMS) to
      a chemotherapy regimen of etoposide (ETOP), ifosfamide (IFOS), and vincristine
      (VCR) with hyperfractionated radiation therapy (XRT). PATIENTS AND METHODS: Sixty
      eight patients aged < 21 years, previously untreated, with clinical group III RMS
      or undifferentiated sarcoma with normal organ function were eligible for this
      study. Chemotherapy was as follows: weeks 0-8: IFOS 1.8 g/m2/day X 5 days every 3
      weeks X 3 (with mesna), ETOP 100 mg/m2/day X 5 days every 3 weeks X 3, and VCR
      1.5 mg/m2/week X 9; weeks 9-16: hyperfractionated XRT (except patients with
      parameningeal tumors with meningeal extension, who received XRT on day 0),
      IFOS/mesna weeks 9, 12, 16, and VCR weeks 9, 10, 11, 12, 16; weeks 20-99;
      IFOS/mesna q 3 weeks X 2, ETOP q 3 weeks X 2, and VCR weekly X 6 weeks. Four drug
      cycles were repeated every 9 weeks, beginning at week 29. In January 1991, the
      duration of therapy was reduced to 12 courses due to emerging evidence of IFOS
      induced renal tubular dysfunction. RESULTS: Of the 62 patients evaluable for
      response, 45 (73%) achieved a complete response. There were three fatal
      toxicities due to infection. Life-threatening neutropenia was seen in 55 of 60
      patients, and life-threatening infections occurred in 27 of 60 patients. Twenty
      five patients (42%) developed some degree of neurotoxicity from vincristine.
      Eleven patients (18%) developed nephrotoxicity, 7 cases of which were severe; 6
      of the 11 patients who developed nephrotoxicity were < 2 years old. CONCLUSIONS:
      This pilot study had toxicity and response rates comparable to the other two
      Intergroup Rhabdomyosarcoma Study (IRS)-IV pilot trials of vincristine
      actinomycin-cyclophosphamide and vincristine-actinomycin-ifosfamide and is,
      therefore, being evaluated in the current IRS randomized trial. Due to the high
      incidence of life-threatening neutropenia and infections, the use of growth
      factors is now routine. Five of 11 patients who developed nephrotoxicity did so
      after more than eight courses of IFOS; therefore, the current randomized trial
      limits IFOS to a total of eight courses.

PMID- 9149742
TI  - Bleeding disorders in Noonan syndrome: three case reports and review of the
      literature.
AB  - PURPOSE: Noonan syndrome (NS) is a congenital disorder characterized by various
      phenotypic features and congenital anomalies. Bleeding disorders are among the
      more serious, common, yet poorly defined complications associated with NS. As a
      means of focusing on these complications, we report three patients with stigmata
      of NS, each of whom had a combination of different hemostatic disorders, and
      review the literature on bleeding disorders in NS. PATIENTS AND METHODS: The
      clinical course and hemostatic abnormalities in three patients with NS were
      studied, and a literature review on NS was undertaken. RESULTS: The three
      patients we report had decreased coagulation factor levels (factors XI and II),
      von Willebrand disease, various levels of thrombocytopenia, and abnormal platelet
      function. The literature review on NS discloses multiple types of hemostatic
      abnormalities and a wide range of clinical presentations. A low level of
      coagulation factor XI is the most frequently described; thrombocytopenia and
      abnormal platelet function are also common. CONCLUSIONS: The existence of various
      types of bleeding disorders within one syndrome is unusual and requires further
      investigation. Recognition of this common complication in children with NS would
      aid both clinical management and understanding of the spectrum, the frequency,
      and perhaps even the basis of the hemostatic defects in this syndrome. We
      recommend performing coagulation screening tests in every patient with NS.

PMID- 9149743
TI  - Primary Burkitt's lymphoma of the liver: report of a case with long-term survival
      after surgical resection and combination chemotherapy.
AB  - PURPOSE: A case of primary Burkitt's cell lymphoma of the liver is reported.
      PATIENT: A 14-year-old Chinese boy presented with a 10-day history of
      postprandial epigastric pain and weight loss. RESULTS: Preoperative imaging
      studies revealed a large solid mass confined to the right lobe of the liver;
      there was no evidence of involvement of other sites. There was serological and
      immunohistochemical evidence of asymptomatic hepatitis B virus infection.
      Complete removal of the mass was achieved by right hepatic lobectomy.
      Histological examination revealed a small noncleaved cell lymphoma of Burkitt's
      type that immunostained positively for B-cell markers. The patient remains well,
      with no evidence of disease > 8 years after surgical resection and combination
      chemotherapy. CONCLUSIONS: Only five cases (two children and three adults) of
      primary small noncleaved cell lymphoma of the liver have been reported. We
      believe this is the second reported case of childhood hepatic lymphoma with long
      term disease-free survival. Further work is needed to elucidate the relationship
      between hepatitis B virus infection and the development of a primary small
      noncleaved lymphoma of the liver.

PMID- 9149744
TI  - Sensorimotor neurotoxicity associated with high-dose deferoxamine treatment.
AB  - PURPOSE: We report a reversible sensorimotor neurotixicity that developed in two
      beta-thalassemic patients treated with high-dose deferoxamine (DFO) for iron
      overload. METHODS: Two patients were treated with high-dose (120 mg/kg/day)
      intravenous DFO for iron overload. RESULTS: Sensorimotor toxicity developed after
      5 and 6 months of treatment, respectively. The development of the neurotoxicity
      did not correlate with the serum ferritin or the ratio of DFO dose to serum
      ferritin. Symptoms resolved in both patients with discontinuation of DFO
      treatment. In 1 patient, symptoms recurred with resumption of DFO treatment.
      CONCLUSIONS: These cases demonstrate that a reversible sensorimotor
      neurotoxicity, a previously unreported toxicity, may complicate DFO therapy, this
      complements the previously reported auditory and visual neurotoxicity associated
      with DFO therapy. Discontinuation of therapy at the time of onset of
      neurotoxicity is recommended, with possible resumption at lower doses.

PMID- 9149746
TI  - Neurodevelopmental side effects of bone marrow transplantation: two case
      illustrations of identical twins.
AB  - PURPOSE: Bone marrow transplantation (BMT), particularly preparative regimens,
      may have a significant impact on the developing nervous system. However, the
      effects of various BMT regimens on children's growth and development have been
      poorly documented to date. Twins serve as ideal subjects to study the impact of
      medical treatment, since they control for nonmedical (genetic and environmental)
      influences upon neurodevelopmental outcome. PATIENTS AND METHODS: Two cases of
      monozygotic twins are presented to illustrate the impact of BMT regimens. Growth
      data and neurocognitive testing are presented for each patient (affected twin) in
      relation to his/her syngeneic BMT donor and case control (control twin). RESULTS:
      These two cases illustrate the growth retardation that has been reported after
      BMT. However, changes in growth trends across twins appear to have begun after
      diagnosis, rather than after BMT per se. Comparisons of cognitive test results
      within these twin pairs illustrate learning problems in the affected twins.
      However, there was also evidence of learning anomalies in the unaffected twins.
      CONCLUSIONS: Results underscore the importance of longitudinal assessment in
      order to identify the side effects of BMT regimens for children. Differences
      across the two cases highlight important research questions regarding variables
      associated with patients, disease, and treatment (e.g., age at the time of BMT,
      previous neurotoxic treatments, underlying disease) and emphasize the importance
      of controls in this line of research.

PMID- 9149745
TI  - Steroid-refractory cutaneous graft-versus-host disease after transplantation of
      haploidentical parental CD34+ cells in children with Down's syndrome and
      recurrent acute leukemia.
AB  - PURPOSE: This study evaluated the feasibility of performing haploidentical CD34+
      selected transplants for children with Down's syndrome (DS) and recurrent
      leukemia. PATIENTS AND METHODS: Within a cohort of 15 children, two patients had
      DS. Transplantation of CD34+ cells from haploidentical parents was performed
      after the children were conditioned with fractionated total body irradiation,
      cyclophosphamide, and antithymocyte globulin (ATG). Graft-versus-host disease
      (GVHD) prophylaxis consisted of cyclosporine and a short course of methotrexate.
      RESULTS: The preparative regimen was well tolerated, and engraftment of
      polymorphonuclear cells and platelets took place promptly (by day 20) in both
      patients with DS. However, both patients with DS experienced severe grade IV GVHD
      that was limited to the skin and was refractory to salvage with high-dose
      methylprednisolone therapy. In one patient, GVHD responded to second-line salvage
      therapy with ATG, but the patient died on day 234 from leukemic relapse. The
      second patient had GVHD that did not respond to ATG and died of multisystem organ
      failure and refractory GVHD on day 44. Two of two DS patients had steroid
      refractory severe acute GVHD of the skin, while only one of 11 evaluated and
      identically treated non-DS patients had severe GVHD (p < 0.05). CONCLUSION: These
      observations in patients who underwent mismatched bone marrow transplantation
      suggests that patients with DS have an increased risk of severe acute GVHD of the
      skin in this context.

PMID- 9149747
TI  - Disseminated Burkitt's lymphoma after kidney transplantation: a case report in a
      boy with Drash syndrome.
AB  - PURPOSE: We discuss the clinical, laboratory findings and treatment of a boy who
      developed Burkitt's lymphoma (BL) after renal transplant and some issues about
      lymphoproliferative disorders after transplantation. METHODS: A 6-year-old boy
      with Drash syndrome developed disseminated Burkitt's lymphoma 38 months after
      transplantation for renal failure. Immunosuppressive therapy had consisted of
      prednisolone and cyclosporine. Polychemotherapy was initiated. RESULTS:
      Polychemotherapy induced rapid and complete remission of the disease without
      major side effects despite the renal transplant allograft and prolonged
      immunosuppression. CONCLUSIONS: A child with posttransplantation B-cell high
      grade lymphoma can be successfully treated with the same chemotherapy regimen
      used for ordinary cases.

PMID- 9149748
TI  - DDAVP therapy controls bleeding in Ehlers-Danlos syndrome.
AB  - PURPOSE: Patients with Ehlers-Danlos syndrome (EDS), especially types IV, VI, and
      VIII, are at increased risk of bleeding, and most do not have specific hemostatic
      deficiencies that would be amenable to replacement therapy. We have investigated
      the ability of DDAVP (desmopressin acetate) to control bleeding in EDS. PATIENTS
      AND METHODS: Two children with EDS, types VIII and VI, presented with hemorrhagic
      symptoms and scheduled surgical procedures. Ivy bleeding times (BTs) were
      measured before and after intravenous (i.v.) DDAVP challenge, and i.v. DDAVP was
      used prophylactically for their procedures. Laboratory testing was performed to
      rule out other hemostatic disorders. RESULTS: Both patients had prolonged BTs
      that corrected following i.v. DDAVP therapy; all other laboratory values were
      normal. Both patients had excellent clinical hemostasis with surgery, and one has
      continued to use intranasal DDAVP to control epistaxis and gingival bleeding.
      CONCLUSIONS: The bleeding time in both patients was corrected with DDAVP, and the
      patients did not have any postoperative bleeding. DDAVP should be considered in
      other patients who have EDS with bleeding tendencies.

PMID- 9149750
TI  - Helicobacter pylori gastritis in a child with sickle cell anemia and recurrent
      abdominal pain.
AB  - PURPOSE: Recurrent abdominal pain is a common complaint in children with sickle
      cell disease. Helicobacter pylori gastritis has recently been described in
      association with recurrent abdominal pain in children. PATIENTS AND METHODS: A
      case report is given of a 16-year-old black male with hemoglobin SS disease
      presenting with recurrent abdominal pain and hematemesis. RESULTS: Endoscopic
      exam of the upper gastrointestinal tract revealed gastritis, and biopsy confirmed
      H. pylori infection. Serology studies demonstrated increased anti-H. pylori
      antibody titers. The young man responded well to treatment, with resolution of
      his symptoms. CONCLUSION: Helicobacter pylori infection is a new diagnostic
      consideration for children with recurrent abdominal pain and should be included
      in the differential diagnosis of children with sickle cell disease, especially
      when abdominal pain is recurrent and accompanied by vomiting. Larger case studies
      will be necessary to determine the true incidence of H. pylori in children with
      sickle cell disease and recurrent abdominal pain.

PMID- 9149749
TI  - Autoimmune liver disease and sickle cell anemia in children: a report of three
      cases.
AB  - PURPOSE: We wish to alert clinicians to the possible association between Sickle
      cell anemia (SCA) and autoimmune liver disease (AIL). METHODS: AIL was diagnosed
      by serologic, histologic and/or cholangiographic studies in patients with known
      SCA. RESULTS: Three schoolaged children with SCA were investigated for increased
      levels of transaminases and/or worsening jaundice. All were diagnosed to have
      AIL. Two patients had autoimmune hepatitis and have responded to
      immunosuppressive therapy, and I had primary sclerosing cholangitis and is stable
      with therapy. CONCLUSIONS: Autoimmune hepatitis and sclerosing cholangitis are
      rare liver disorders of childhood, but may occur with greater frequency in
      patients with SCA. Early diagnosis and treatment is essential to prevent
      progression to liver cirrhosis. This association may provide a clue to the
      etiology of AIL and warrants further investigation.

PMID- 9149751
TI  - Transient erythroblastopenia of childhood (TEC) presenting as leukoerythroblastic
      anemia.
AB  - PURPOSE: The diagnosis of transient erythroblastopenia of childhood (TEC) is
      usually straightforward, with temporary cessation of red blood cell production
      resulting in normocytic normochromic anemia, reticulocytopenia, and bone marrow
      erythroblastopenia. We describe here a case of TEC presenting with features of
      leukoerythroblastic anemia. To our knowledge, this is the first such report for
      TEC. PATIENT AND METHODS: The case of a 1-year-old girl is described who had a
      leukoerythroblastic anemia. Bone marrow examination and clinical course indicated
      that the anemia had a benign etiology-TEC. RESULTS: The patient presented with
      anemia, leukocytosis, and a left shift, with metamyelocytes, myelocytes,
      myeloblasts, and nucleated red cells in the circulation. There was no apparent
      viral etiology, and the bone marrow aspirate findings were consistent with a
      recovering marrow. After transfusion, the patient had an uneventful recovery from
      TEC. CONCLUSION: TEC can cause leukoerythroblastic anemia. TEC with this
      presentation is clinically similar to TEC without leukoerythroblastosis, but
      other causes of leukoerythroblastosis need to be excluded.

PMID- 9149752
TI  - Hepatoblastoma metastatic to brain: prolonged survival after multiple surgical
      resections of a solitary brain lesion.
AB  - PURPOSE: Pulmonary metastases of hepatoblastoma confined to the lung have been
      cured using therapy that included radical surgical resection. We report the case
      of a child with a hepatoblastoma metastatic to brain that was successfully
      treated with multiple surgical resections, irradiation, and chemotherapy. The
      case demonstrates that such an approach, employing aggressive surgery, can
      produce durable remission of an extrapulmonary metastasis with hepatoblastoma.
      PATIENTS AND METHODS: A 17-month-old girl presented with a hepatoblastoma that
      remained unresectable after chemotherapy and irradiation and underwent orthotopic
      liver transplantation 14 months after diagnosis. After twice undergoing surgical
      resections of pulmonary metastases 22 and 31 months from diagnosis, 1 month later
      (32 months from diagnosis), she developed a solitary metastatic right brain
      lesion that later recurred twice in the same location, 5 and 6 years from initial
      diagnosis. Each time she underwent surgical resection of the brain lesion and
      received local irradiation after the first two resections and chemotherapy after
      the third. At the last surgery, resection was continued until histologically
      negative tumor margins were obtained. RESULTS: The child is currently without
      evidence of disease or neurological deficit 10.5 years from initial diagnosis.
      CONCLUSION: The durable remission achieved after multiple resections of the
      recurrent solitary cerebral metastasis in this child demonstrates that an
      aggressive surgical approach to extrapulmonary metastases in such a setting can
      contribute to prolonged survival, just as has been shown with isolated metastatic
      pulmonary disease.

PMID- 9149753
TI  - Disseminated intrathoracic desmoplastic small round-cell tumor: a case report.
AB  - PURPOSE: Recently recognized as a distinct clinicopathologic entity, desmoplastic
      small round-cell tumors typically affect young men. These aggressive tumors
      usually arise in the abdomen; other sites of primary disease have been described
      only rarely. We report the case of an extraabdominal primary tumor with
      widespread dissemination, including the subcutaneous tissue, a previously
      unrecognized metastatic site. PATIENT AND METHODS: We describe the case of a 16
      year-old boy with a primary extraabdominal metastatic desmoplastic small round
      cell tumor. RESULTS: Our patient had a primary intrathoracic desmoplastic small
      round-cell tumor and widespread dissemination involving the subcutaneous tissue,
      kidney, liver, bone, and lymph nodes. Histopathologic analysis found intense
      desmoplasia and polyphenotypic expression of neural, muscle, and epithelial
      markers. Reverse transcriptase-polymerase chain reaction analysis of fresh tumor
      tissue confirmed the characteristic EWS-WT1 transcript. CONCLUSIONS: Broader than
      originally anticipated, the clinical spectrum of desmoplastic small round-cell
      tumors continues to evolve. Primary intrathoracic tumors with soft-tissue
      dissemination and polyphenotypic expression should prompt suspicion of this
      malignancy. Molecular analysis of fresh tumor tissue is an important adjunct to
      diagnosing this rare neoplasm.

PMID- 9149754
TI  - Case of neuroblastoma with differing cytologic and molecular biologic features at
      primary and metastatic sites.

PMID- 9149755
TI  - Spontaneous remission of juvenile chronic myelomonocytic leukemia in an infant
      with Noonan syndrome.

PMID- 9149756
TI  - Turner syndrome and myelodysplastic syndrome. No reason to alert.

PMID- 9149757
TI  - Successful treatment of metastatic poor risk extragonadal germ cell tumor in a 15
      year-old boy.

PMID- 9149758
TI  - Aging and the mechanisms underlying head and postural control during voluntary
      motion.
AB  - The quality of sensory information that is necessary for balance and postural
      stability will depend to a great extent on head stability as the body moves. How
      older persons coordinate head and body motion for balance during volitional
      activities is not known. The purposes of this article are to present a basis for
      understanding the influence of aging on head control during voluntary motion and
      to discuss some data that demonstrate how elderly people might control head
      movement to improve gaze and the quality of vestibular inputs. A "top-down" or
      "head-first" control scheme is proposed as the mechanism that elderly people
      without disabilities use to maintain head position during self-initiated motion.
      This type of control ensures that the angular position of the head in space
      remains relatively constant--through the use of a head-stabilization-in-space
      (HSS) strategy--regardless of the magnitude or direction of displacements in the
      body's center of force. The HSS strategy is thought to reduce potential
      ambiguities in the interpretation of sensory inputs for balance and is derived
      primarily from a geocentric (orientation to the vertical) frame of reference.
      Egocentric (orientation of the head with respect to the body) or exocentric
      (orientation to objects in the environment) frames of reference, however, refine
      the control of head stabilization. Preliminary research suggests that elderly
      people use the HSS strategy to control head pitch during difficult balance tasks.
      These findings, if supported by more definitive studies, may be useful in the
      treatment of patients with balance disorders. The treatment of patients with
      balance dysfunction is discussed within the conceptual framework of a "head
      first" organization scheme.

PMID- 9149759
TI  - Light touch contact as a balance aid.
AB  - Canes and crutches are commonly used mobility aids, and most studies of their use
      have focused on issues equating support with the resulting decrease in force
      required of the affected limb. Clinicians, however, often observe patients with
      poor balance control using light touch of surrounding objects and surfaces to
      stabilize themselves while standing and walking. A series of studies have shown
      that sensory input to the hand and arm through contact cues at the fingertip or
      through a cane can reduce postural sway in individuals who have no impairments
      and in patients without a functioning vestibular system, even when contact force
      levels are inadequate to provide physical support of the body. This article
      summarizes these results, which have implications for design considerations of
      rehabilitation aids. Mobility devices or rehabilitation aids that provide
      feedback about applied force or enhance existing resolution of applied force
      changes across the skin surface may lead to new rehabilitation techniques.

PMID- 9149760
TI  - The role of limb movements in maintaining upright stance: the "change-in-support"
      strategy.
AB  - Change-in-support strategies, involving stepping or grasping movements of the
      limbs, are prevalent reactions to instability and appear to play a more important
      functional role in maintaining upright stance than has generally been
      appreciated. Contrary to traditional views, change-in-support reactions are not
      just strategies of last resort, but are often initiated well before the center of
      mass is near the stability limits of the base of support. Furthermore, it appears
      that subjects, when given the option, will select these reactions in preference
      to the fixed-support "hip strategy" that has been purported to be of functional
      importance. The rapid speed of compensatory change-in-support reactions
      distinguishes them from "volitional" arm and leg movements. In addition,
      compensatory stepping reactions often lack the anticipatory control elements that
      are invariably present in non-compensatory stepping, such as gait initiation.
      Even when present, these anticipatory adjustments appear to have little
      functional value during rapid compensatory movements. Lateral destabilization
      complicates the control of compensatory stepping, a finding that may be
      particularly relevant to the problem of falls and hip fractures in elderly
      people. Older adults appear to have problems in controlling lateral stability
      when stepping to recover balance, even when responding to anteroposterior
      perturbation. Increased understanding and awareness of change-in-support
      reactions should lead to development of new diagnostic and therapeutic approaches
      for detecting and treating specific causes of imbalance and falling in elderly
      people and in patients with balance impairments.

PMID- 9149761
TI  - Locomotion in patients with spinal cord injuries.
AB  - Following central motor lesions, two forms of reorganization can be observed that
      lead to improved mobility: (1) the development of increased muscle tone and (2)
      the activation of spinal locomotor centers induced by specific treadmill
      training. Tension development is different from normal during spastic gait and
      appears to be independent of exaggerated monosynaptic stretch reflexes.
      Exaggerated stretch reflexes are associated with an absence or reduction of
      functionally essential polysynaptic reflexes. Based on observations of the
      locomotor capacity of the spinal cat, recent studies have indicated that spinal
      locomotor centers can be activated and trained in patients with complete or
      incomplete paraplegia when the body is partially unloaded. The level of
      electromyographic activity in the gastrocnemius muscle, however, is considerably
      lower in patients with central motor lesions than in persons without neurological
      impairments. During the course of a daily locomotor training program, the
      amplitude of gastrocnemius muscle electromyographic activity increases during the
      stance phase and inappropriate tibialis anterior muscle activity decreases. Such
      training programs can improve the ability of patients with incomplete paraplegia
      to walk on stationary surfaces. This article reviews the pathophysiology and
      functional importance of increased muscle tone and the effects of treadmill
      training on the locomotor pattern underlying new attempts to improve the mobility
      of patients with paraplegia.

PMID- 9149762
TI  - Postural perturbations: new insights for treatment of balance disorders.
AB  - This article reviews the neural control of posture as understood through studies
      of automatic responses to mechanical perturbations. Recent studies of responses
      to postural perturbations have provided a new view of how postural stability is
      controlled, and this view has profound implications for physical therapy
      practice. We discuss the implications for rehabilitation of balance disorders and
      demonstrate how an understanding of the specific systems underlying postural
      control can help to focus and enrich our therapeutic approaches. By understanding
      the basic systems underlying control of balance, such as strategy selection,
      rapid latencies, coordinated temporal spatial patterns, force control, and
      context-specific adaptations, therapists can focus their treatment on each
      patient's specific impairments. Research on postural responses to surface
      translations has shown that balance is not based on a fixed set of equilibrium
      reflexes but on a flexible, functional motor skill that can adapt with training
      and experience. More research is needed to determine the extent to which
      quantification of automatic postural responses has practical implications for
      predicting falls in patients with constraints in their postural control system.

PMID- 9149763
TI  - Rehabilitation of balance in two patients with cerebellar dysfunction.
AB  - The treatment of two patients with cerebellar dysfunction is described. One
      patient was a 36-year-old woman with a 7-month history of dizziness and
      unsteadiness following surgical resection of a recurrent pilocystic astrocytoma
      located in the cerebellar vermis. The other patient was a 48-year-old man with
      cerebrotendinous xanthomatosis (CTX) and diffuse cerebellar atrophy, and a 10
      year history of progressive gait and balance difficulties. Each patient was
      treated with a 6-week course of physical therapy that emphasized the practice of
      activities that challenged stability. The patient with the cerebellar tumor
      resection also performed eye-head coordination exercises. Each patient had weekly
      therapy and performed selected balance retraining exercises on a daily basis at
      home. Measurements taken before and after treatment for each patient included
      self-perception of symptoms, clinical balance tests, and stability during
      selected standing and gait activities; for the patient with the cerebellar tumor
      resection, vestibular function tests and posturography were also performed. Both
      patients reported improvements in symptoms and demonstrated similar improvements
      on several kinematic indicators of stability during gait. The patient with the
      cerebellar tumor resection improved on posturography following treatment, whereas
      the patient with CTX improved on clinical balance tests. This case report
      describes two individualized treatment programs and documents functional
      improvements in two patients with different etiologies, durations, and clinical
      presentations of cerebellar dysfunction. The outcomes suggest that patients with
      cerebellar lesions, acute or chronic, may be able to learn to improve their
      postural stability.

PMID- 9149764
TI  - Balance retraining after stroke using force platform biofeedback.
AB  - Balance is a somewhat ambiguous term used to describe the ability to maintain or
      move within a weight-bearing posture without falling. Balance can further be
      broken down into three aspects: steadiness, symmetry, and dynamic stability.
      Steadiness refers to the ability to maintain a given posture with minimal
      extraneous movement (sway). The term symmetry is used to describe equal weight
      distribution between the weight-bearing components (eg, the feet in a standing
      position, the buttocks in a sitting position), and dynamic stability is the
      ability to move within a given posture without loss of balance. All of these
      components of balance (steadiness, symmetry, and dynamic stability) have been
      found to be disturbed following stroke. Balance testing of patients with
      hemiparesis secondary to stroke has revealed a greater amount of postural sway
      during static stance, asymmetry with greater weight on the nonparetic leg, and a
      decreased ability to move within a weight-bearing posture without loss of
      balance. Furthermore, research has demonstrated moderate relationships between
      balance function and gait speed (r = -.67 and .42, respectively), independence (r
      = .62), appearance (defined as "significantly abnormal," "slightly abnormal," and
      "nearly normal") (r = .50), dressing (r.55-.69), wheelchair mobility (r = .51),
      and reaching (r = .49-.78). Thus, a principal construct within physical therapy
      practice is the reestablishment of balance function in patients following stroke.
      Recent advances in technology have resulted in the commercial availability of
      numerous force platform systems for the retraining of balance function in patient
      populations, including patients with stroke. These systems are designed to
      provide visual or auditory biofeedback to patients regarding the locus of their
      center of force (COF) or center of pressure (COP), as well as training protocols
      to enhance stance symmetry, steadiness, and dynamic stability. Typical force
      platform biofeedback systems consist of at least two force plates to allow the
      weight on each foot to be determined, a computer and monitor to allow
      visualization of the COF or COP, and software that provides training protocols
      and data analysis capabilities. Some units allow auditory feedback in addition to
      the visual feedback in response to errors in performance.

PMID- 9149765
TI  - Importance of conventional units.

PMID- 9149766
TI  - Autologous blood: always safer?

PMID- 9149767
TI  - Activation of the contact system by filtration of platelet concentrates with a
      negatively charged white cell-removal filter and measurement of venous blood
      bradykinin level in patients who received filtered platelets.
AB  - BACKGROUND: Several recent reports have described hypotensive transfusion
      reactions in patients receiving platelet concentrates (PCs) filtered through
      white cell-reduction filters. It is well known that a negatively charged surface
      activates the contact system, consisting of factor XII, prekallikrein, and high
      molecular-weight kininogen. STUDY DESIGN AND METHODS: To clarify the mechanisms
      of these hypotensive reactions, the possibility that white cell-reduction
      filtration activates the contact system was examined. Venous blood plasma
      bradykinin levels were also measured in patients receiving PC transfusions
      through filters. RESULTS: None of the measured values were changed by filtration
      through a positively charged filter. However, filtration through a negatively
      charged filter resulted in a decrease in the amounts of prekallikrein and an
      increase in the amount of bradykinin generated, which indicated the activation of
      the contact system. The bradykinin level was inversely related to the activity of
      angiotensin-converting enzyme (ACE) in the PCs and was elevated by addition of an
      ACE inhibitor. Although the venous blood plasma bradykinin level did not change
      in two patients with a normal ACE activity during PC transfusion through the
      negatively charged filter, two patients who had decreased ACE activity, showed a
      significant increase in bradykinin during the transfusion. CONCLUSION: These
      results suggest that the generation of a large amount of bradykinin by filtration
      of PCs through a negatively charged filter might cause hypotensive reactions in
      patients with decreased ACE activity. The clinical significance of bradykinin
      generation requires further study.

PMID- 9149768
TI  - A point score system for predicting the likelihood of blood transfusion after hip
      or knee arthroplasty.
AB  - BACKGROUND: Given the high cost of autologous blood donation for elective
      surgery, it would be desirable to predict which patients are most likely to
      benefit from the procedure. The purpose of this study was to develop a point
      score system for predicting the likelihood of blood transfusion in hip and knee
      arthroplasty. STUDY DESIGN AND METHODS: A database of 599 patients undergoing
      elective surgery at a teaching hospital was used for the analysis. Variables were
      analyzed to determine their univariate association with postoperative blood
      transfusion. Significant factors were entered into a multiple logistic regression
      model, and a point score system was developed on the basis of the regression
      coefficients. Four strata of transfusion risk were constructed. RESULTS: Factors
      independently associated with blood transfusion included preoperative hemoglobin,
      type of arthroplasty, primary versus revision surgery, autologous donor status,
      and patient weight. Four factors were used to create a point score system with
      four strata. The likelihood of blood transfusion for patients in the four risk
      strata was 1.7, 11.0, 40.0, and 78.3 percent. The calculated area under the
      receiver operating characteristic curve was 0.86. CONCLUSION: The likelihood of a
      postoperative blood transfusion can be predicted by using this simple point score
      system. Autologous blood donation can subsequently be targeted to the high-risk
      patients.

PMID- 9149769
TI  - Generation of interleukin 8 in stored apheresis platelet concentrates and the
      preventive effect of prestorage ultraviolet B radiation.
AB  - BACKGROUND: Several recent studies have reported both the generation of
      cytokines, including interleukin (IL)-1 beta, IL-6, tumor necrosis factor alpha
      (TNF-alpha), and IL-8, in the supernatants of stored platelet concentrates (PCs)
      and the implications of this generation in febrile nonhemolytic transfusion
      reactions. Prestorage filtration is regarded as highly effective in the
      prevention of cytokine generation. STUDY DESIGN AND METHODS: Studies evaluated 1)
      the levels of these cytokines in apheresis PCs during storage, 2) the effects of
      white cell inactivation by ultraviolet B or gamma-radiation on the generation of
      cytokines, and 3) the effects of poststorage filtration on cytokine levels. The
      apheresis PCs were treated by either ultraviolet B radiation (20,000 J/m2), gamma
      radiation (30 Gy), or filtration. Samples were collected sequentially on various
      days after storage. Cytokines were determined by enzyme-linked immunosorbent
      assay. RESULTS: The average white cell count in 15 PCs tested was 2.58 +/- 0.7 x
      10(6) per mL (range, 0.7-10 x 10(6)/mL). A detectable level of IL-8 was found at
      3 days of storage, and the levels of this cytokine increased progressively with
      increasing storage time, ranging from 1.6 to 35,280 pg per mL on Day 5 and from
      2.7 to 83,601 pg per mL on Day 8. Reverse transcriptase-polymerase chain reaction
      analysis showed that the level of IL-8 paralleled the expression of IL-8
      transcripts. The levels of IL-1 beta, IL-6, TNF-alpha, and monocyte chemotactic
      protein-1 were very low, even on Day 8. Ultraviolet B-radiated PCs failed to
      generate IL-8, even at 8 days of storage, whereas levels of IL-8 in gamma
      radiated PCs were similar to those in nonirradiated PCs. Poststorage filtration
      of PCs with a negatively charged polyester filter, but not with a positively
      charged one, markedly reduced the levels of IL-8. CONCLUSION: Of the cytokines
      tested, IL-8 had the most evident generation in apheresis PCs during storage.
      Prestorage inactivation of white cells by ultraviolet B radiation, but not by
      gamma-radiation, was effective in preventing the generation of cytokines during
      the storage of PCs.

PMID- 9149770
TI  - Improvement of platelet storage conditions by using new polyolefin containers.
AB  - BACKGROUND: Storage of pooled platelet concentrates (PCs) with yields above 3.0 x
      10(11) platelets per unit in a 1-L PL-732 polyolefin container for 5 days often
      results in a drop in pH to below 6.0. Recently, new oxygen-permeable platelet
      containers (1-L PL-2410, 1-L and 1.5-L Compoflex) have been developed. The
      maximal platelet storage capacities of the new containers and the PL-732 were
      compared. STUDY DESIGN AND METHODS: Large platelet pools (n = 27) with platelet
      concentrations between 1.2 and 1.4 x 10(11) per L were made from 3 to 5 PCs
      prepared from buffy coats. The pools were divided in equal volumes among the PL
      732 and the three new platelet containers. Platelet counts in the PCs ranged from
      1.0 to 5.0 x 10(11) per unit. All PCs were stored on a flatbed shaker at 22 +/- 2
      degrees C and evaluated on Days 1, 3, 5, and 7 by measuring platelet count, pH,
      pO2, pCO2, HCO3-, glucose, lactate, platelet swirling, and soluble p-selectin.
      RESULTS: Day 7 storage of PCs (n = 6) with yields between 3.0 and 4.0 x 10(11)
      platelets in PL-732 showed mean +/- SD pH values of 5.93 +/- 0.05 and lactate
      values of 32.3 +/- 7.9 mmol per L; in 4 of these 6 PCs, pH was below 6.0. In
      contrast, storage of these PCs in 1-L PL-2410 and 1.5-L Compoflex containers and
      of 2 of these 6 PCs in 1-L Compoflex containers showed pH values above 6.8.
      Lactate values were 15.5 +/- 1.3, 15.3 +/- 1.8, and 19.5 +/- 4.7 mmol per L,
      respectively (p < 0.001 vs. PL-732). The platelet storage capacity of the new
      containers with platelet yields between 4.0 and 5.0 x 10(11) per unit (n = 6) was
      evaluated. Day 7 storage of these PCs in the 1.5-L Compoflex showed an average pH
      value of 6.74 +/- 0.20; in 2 of 6 PCs, pH was below 6.8. The average pH value in
      the PL-2410 was 6.38 +/- 0.31, and in all PCs, pH was below 6.8. Average lactate
      values were 17.8 +/- 5.7 and 25.8 +/- 5.6 mmol per L (p < 0.05), respectively.
      Soluble p-selectin values on Day 7 of storage increased approximately twofold in
      all PCs. CONCLUSION: The new oxygen-permeable containers showed platelet quality
      comparable to that with the PL-732 and for longer storage periods and at higher
      platelet counts.

PMID- 9149771
TI  - High-yield platelet concentrates attainable by continuous quality improvement
      reduce platelet transfusion cost and donor exposure.
AB  - BACKGROUND: Donor exposure risk and cost in platelet transfusion practice can be
      limited by increasing the recovery of platelets from donor units. STUDY DESIGN
      AND METHODS: This study presents results of continuous quality improvement
      efforts in platelet production and compares the in vivo therapeutic efficacy of
      currently produced platelet concentrates (PCs) with that of apheresis platelets.
      Production quality improvement measures included optimization of instrument
      performance (rotor speed trials), process (massaging whole-blood units, using cup
      liners, limiting spin-expression time, and refining plasma expression technique),
      and staff (intensive training with observation and ongoing quality control data
      feedback). Corrected count increments and increments per kg were calculated for
      transfusions of 4 pooled PCs and apheresis platelets over a 30-day period.
      RESULTS: The mean number of platelets per PC increased from 5.5 x 10(10) in 1975
      to 9.69 x 10(10) in 1994. The mean platelet dose was 3.78 x 10(11) for 4 PCs and
      4.17 x 10(11) for apheresis platelets. A total of 34 pooled PCs and 17 apheresis
      platelets was transfused to 21 patients. The mean increment, the increment per
      kg, and the corrected count increment were, respectively, 31 x 10(3) per microL,
      4.8 x 10(2) per microL, and 14,700 for 4 PCs and 35.4 x 10(3) per microL, 5.4 x
      10(2) per microL, and 14,700 for apheresis platelets. Differences were not
      significant. CONCLUSION: Therapeutic efficacy comparable to that of apheresis
      platelets can be obtained with 4 high-yield PCs.

PMID- 9149772
TI  - A multicenter evaluation of the routine use of a new white cell-reduction
      apheresis system for collection of platelets.
AB  - BACKGROUND: Residual white cells (WBCs) cause serious side effects in platelet
      transfusion. An in-line WBC-reduction system based on fluidized particle bed
      technology was recently developed as a modification of an existing
      plateletpheresis system. STUDY DESIGN AND METHODS: In an investigational phase,
      three flow profiles were evaluated using prototype software in five centers, each
      using their standard conditions. In the confirmatory phase, the released software
      was tested in three centers. WBCs were counted in two full Nageotte grids
      (dilution 1-in-5). RESULTS: With the prototype software, WBC levels were always
      below 1 x 10(6) per procedure (median, 25,000/procedure; n = 314). One profile
      proved to be superior to the other two with respect to platelet yield and
      residual WBCs, and it was incorporated in the released WBC-reduction system,
      together with a built-in process control. Median residual WBCs in these WBC
      reduction system components not rejected by the process control were 19,000 per
      procedure (n = 211/225 total), with 99.5 percent of the platelet components
      having less than 1 x 10(6) WBCs. CONCLUSION: The protocol selected in the initial
      phase, now available as a WBC-reduction system, results in platelet concentrates
      with very low residual WBC levels. This satisfies even the most stringent
      criteria for WBC reduction in platelets, without the platelet loss typically seen
      with conventional fiber filtration.

PMID- 9149773
TI  - Differentiation of anti-D, -C, and -G: clinical relevance in alloimmunized
      pregnancies.
AB  - BACKGROUND: The differentiation of anti-D, -C, and -G specificities is seldom
      considered clinically important in pretransfusion testing. However,
      distinguishing these antibody specificities in alloimmunized pregnancies may be
      essential. The clinical prognosis as well as Rh immune globulin prophylaxis
      depends on the accurate identification of these antibodies. CASE REPORT: A
      pregnant woman, para 1 gravida 4, who had received Rh immune globulin at
      appropriate intervals during her previous pregnancies was reported to have anti-D
      (titer = 4) and anti-C (titer = 32). Differential adsorption and elution studies
      showed that the patient had anti-C and anti-G, but not anti-D. This case prompted
      retrospective examination of the sera from six other women with anti-D and anti-C
      who were referred to a high-risk pregnancy clinic. Of six pregnant women reported
      to have anti-D and anti-C; two had anti-D, -C, and -G; three had anti-D and -G,
      but not anti-C; and one had anti-C and -G, but not anti-D. This last is similar
      to the index case. CONCLUSION: Cases of pregnant women with anti-C and -G, but
      not anti-D, are not infrequent. Studies to differentiate anti-D, -C, and -G
      should be performed on alloimmunized pregnant women presumptively identified as
      having anti-D and anti-C when the medical history (Rh immune globulin
      prophylactic therapy) and/or titer values (e.g., anti-C titer higher than anti-D
      titer) suggest that anti-D may not actually be present. Rh immune globulin has
      not failed in these patients, and they should receive this therapy during
      pregnancy to prevent immunization to D.

PMID- 9149774
TI  - Removing IgG antibodies from intact red cells: comparison of acid and EDTA, heat,
      and chloroquine elution methods.
AB  - BACKGROUND: To accurately phenotype red cell from patients with a positive direct
      antiglobulin test (DAT), nonlytic elution procedures were assessed for their
      ability to dissociate IgG from antibody-coated red cells without altering red
      cell antigen expression. STUDY DESIGN AND METHODS: Antibodies coating red cells
      that were sensitized in vivo (warm-reactive autoantibodies: 8 patients) or in
      vitro (42 alloantibodies) were eluted by using glycine-HCl and EDTA (acid/ EDTA),
      heat (56 degrees C, 10 min), or chloroquine method. RESULTS: Acid/EDTA elution
      gave the best results, reducing DAT positivity to microscopic levels or rendering
      the DAT negative in 48 of 50 instances, whereas 4 samples remained resistant to
      heat elution and 24 to chloroquine. Standard DAT agglutination scores
      demonstrated that both acid/EDTA and heat elution were superior to the
      chloroquine method (p < 0.0001). With the gel low-ionic-strength saline indirect
      antiglobulin test, acid/ EDTA was superior to heat (p < 0.001). Overall, acid/
      EDTA elution dissociated more antibodies than heat (p < 0.0001), especially for
      Kell system (K, k, Kpa, Kpb) alloantibodies. Common red cell antigens, other than
      Kell system antigens, were unaffected by acid/EDTA elution. In contrast, the
      expression of most blood group antigens was diminished after heat elution.
      However, it was possible to type red cell antigens by using gel low-ionic
      strength saline indirect antiglobulin tests or tube agglutination methods.
      CONCLUSION: Although heat elution may be used on a limited basis, the acid/EDTA
      method appears to be the procedure of choice for typing red cell coated with warm
      reactive IgG alloantibodies or autoantibodies.

PMID- 9149775
TI  - Detection and differentiation of platelet-specific antibodies by flow cytometry:
      the bead-mediated platelet assay.
AB  - BACKGROUND: Platelet-reactive antibodies cause a number of clinical disorders.
      The detection and differentiation of these antibodies are prerequisites for the
      adequate treatment of these disorders. The bead-mediated platelet assay described
      here enables the detection and differentiation of platelet-bound antibodies by
      the use of flow cytometry. STUDY DESIGN AND METHODS: The bead-mediated platelet
      assay is based on the isolation of human platelet glycoproteins by using flow
      cytometric standardization beads after the incubation of typed platelets with
      human sera. The specificity and sensitivity of this assay were tested with five
      sera, each containing a known platelet-reactive antibody. The monoclonal antibody
      specific immobilization of platelet antigens assay was used as a reference test.
      RESULTS: The bead-mediated platelet assay was able to determine the glycoprotein
      specificity of the antibody without cross-reactions in every case. In serial
      dilution tests, the bead-mediated platelet assay was able to detect the
      antibodies at higher dilutions than the monoclonal antibody-specific
      immobilization of platelet antigen assay. Total test time was 3.5 hours.
      CONCLUSION: The bead-mediated platelet assay is a fast and reliable method for
      the detection and differentiation of platelet-reactive antibodies.

PMID- 9149776
TI  - Factors affecting mobilization of CD34+ cells in normal donors treated with
      filgrastim.
AB  - BACKGROUND: Multiple days of apheresis are required for some normal peripheral
      blood progenitor cell (PBPC) donors, to ensure a sufficient collection of CD34+
      cells for allografting. It would be of practical value to be able to identify the
      patients with poor mobilization on the basis of simple pretreatment clinical or
      hematologic variables. STUDY DESIGN AND METHODS: Clinical characteristics and
      laboratory data for 119 normal PBPC donors who underwent apheresis on Days 4 to 6
      of treatment with granulocyte-colony-stimulating factor (filgrastim) were
      analyzed for correlations with CD34+ cell yield from the first day of apheresis.
      RESULTS: The CD34+ cell yield was significantly lower in donors who were more
      than 55 years of age, who underwent apheresis on Day 4 of filgrastim therapy, or
      who were not obese. There were weak direct correlations between CD34+ cell yield
      and the baseline white cell count, preapheresis white cell count, and
      preapheresis mononuclear cell count, and there was a weak inverse correlation
      with age. Twenty-one donors (18%) were considered to have poor mobilization (< 20
      x 10(6) CD34+ cells/L blood processed). In the multivariate analysis, the only
      significant factor was age greater than 55 years, which conferred a 3.8 times
      greater risk (95% CI, 1.1-13.7) of poor mobilization (p = 0.04). However, poor
      mobilization occurred in all age groups, so the predictive value of the model was
      low. CONCLUSION: Donor variables correlated with CD34+ cell yield only weakly, so
      no particular clinical characteristic can be used to exclude an individual as a
      PBPC donor if he or she is otherwise suitable for the apheresis procedure.

PMID- 9149777
TI  - Transmission of human immunodeficiency virus through blood transfusion: the use
      of lookback and traceback approaches to optimize recipient identification in a
      regional population.
AB  - BACKGROUND: The purpose of this study was to define the epidemiologic features of
      the transmission of human immunodeficiency virus (HIV) by blood transfusion in a
      region of Canada between 1980 and 1985 and the results of intensive recipient
      identification practices. STUDY DESIGN AND METHODS: Lookback (notification of all
      recipients of blood from an HIV-infected donor) and traceback (identification of
      the HIV-infected source donor, after an HIV-infected recipient of blood cites
      transfusion as a risk for infection) programs were established linking (with
      patient consent) a transfusion service and an HIV clinic to identify HIV-infected
      donors and the recipients of their blood. RESULTS: Twenty-two cases of documented
      HIV infection and 26 cases of presumed infection were found in local blood
      recipients. Twenty-eight recipients have died of causes unrelated to HIV. Twelve
      recipients have developed AIDS. Six of the seven living recipients have yet to
      develop an AIDS condition. These 48 infections have been linked to 11 donors who
      have subsequently tested positive for HIV infection. Six donors were found on
      subsequent blood donation. Five donors were found by traceback. CONCLUSION: Forty
      eight recipients of blood from donors who subsequently tested positive for HIV
      were identified in a low-prevalence area. Active lookback and traceback programs
      linking a transfusion service and an HIV clinic were successful in identifying
      infected recipients.

PMID- 9149779
TI  - Autologous donation error rates in Canada.
AB  - BACKGROUND: Although certain transfusion risks are eliminated by the use of
      autologous blood, clerical errors may still occur. In addition, because of
      differences in donor selection criteria and donor-patient expectations, the
      consequences of certain errors may be different in autologous and allogeneic
      donations. STUDY DESIGN AND METHODS: In January 1996, autologous donation error
      rates in Canada from 1989 to November 1995 were estimated by 1) a detailed
      questionnaire sent to hospitals supplied by the Canadian Red Cross, Blood
      Services, Transfusion Center of Quebec at Montreal autologous donation program (n
      = 31), 2) a review of that institution's quality assurance non-compliance
      reports, and 3) a detailed questionnaire sent to other Canadian Red Cross centers
      with autologous donation programs (n = 16) and hospital-based autologous programs
      in Canada (n = 3). The total number of autologous donations collected was
      determined from Canadian Red Cross annual reports and information supplied by
      hospital-based programs. RESULTS: There were 113 errors reported for 16,873 units
      collected by the Montreal center (1/149 units) based on collection center and
      hospital data. The most frequent errors were the late receipt of units for
      surgery (25% of errors) or the receipt of units in the wrong hospital (23%).
      Other Canadian programs reported 166 errors for approximately 53,500 units
      collected (1/322 units). However, this figure was based mainly on collection
      center, and not hospital, data. The most frequent errors were in labeling (48%)
      and component preparation (25%). One unit of autologous fresh-frozen plasma was
      transfused to the wrong recipient. Errors were more frequent if components were
      produced, if units were drawn in hospitals for interhospital transfer, or it
      units were shipped between Red Cross centers. CONCLUSION: Errors are not
      infrequent in autologous donation programs. Autologous transfusion should not be
      considered as being without risk.

PMID- 9149780
TI  - Relationship of the time of storage and transfusion reactions to platelet
      concentrates from buffy coats.
AB  - BACKGROUND: Transfusion reactions to platelet concentrates prepared from buffy
      coats (BC-PCs) were reviewed to determine the effect of some variables of BC-PC
      preparation and storage: time of BC storage before BC-PC preparation (1-2 days);
      time of BC-PC storage before transfusion (1-5 days); no white cell reduction
      versus laboratory and bedside BC-PC white cell reduction. STUDY DESIGN AND
      METHODS: A multiple linear logistic regression model was used by which the
      relative effect of one variable is expressed as the relative risk of transfusion
      reaction against a baseline level (1-day storage, no white cell reduction).
      RESULTS: During the 14 months of study, a total of 2707 BC-PC transfusions were
      given to 192 patients; 37 reactions (1.4%) were reported in 25 patients (13%).
      The transfusion reactions were febrile, nonhemolytic in 23 cases; allergic in 5;
      febrile and allergic in 2; and other in 7. The relative risk of transfusion
      reaction to BC-PCs prepared from BCs stored for 2 days was 1.98 times that to BC
      PCs prepared from BCs stored for 1 day (p = 0.07). The relative risk of
      transfusion reaction of 5-day-old BC-PCs was 10.7 times that of 1-day-old BC-PCs
      (p = 0.001). The relative risk of transfusion reactions of BC-PCs white cell
      reduced in the laboratory and at the bedside were 0.65 (p = 0.3) and 1.87 (p =
      0.1) times, respectively, that of non-white cell-reduced BC-PCs. CONCLUSION: Time
      of storage seems to be an important variable associated with BC-PC transfusion
      reaction.

PMID- 9149778
TI  - Transmission of parvovirus B19 by coagulation factor concentrates exposed to 100
      degrees C heat after lyophilization.
AB  - BACKGROUND: Double inactivation by solvent/detergent treatment plus heating at
      100 degrees C for 30 minutes after lyophilization has been adopted to improve
      viral safety of factor VIII and factor IX concentrates, particularly with respect
      to non-lipid-enveloped viruses. The aim of this study was to evaluate the safety
      of concentrates exposed to these virucidal methods. STUDY DESIGN AND METHODS:
      Twenty-six previously untreated hemophiliacs, 19 with factor VIII deficiency and
      7 with factor IX deficiency, were investigated in a prospective multicenter study
      over a 12-month follow-up period by the use of serologic and virologic markers
      for lipid- and non-lipid-enveloped viruses (human immunodeficiency virus types 1
      and 2; hepatitis A, B, and C viruses; B19 parvovirus antibodies; and B19 DNA).
      Overall, 270,000 U of factor VIII and 102,000 U of factor IX concentrate were
      administered during the study period. RESULTS: None of the 26 patients
      seroconverted for human immunodeficiency virus or hepatitis C virus. Hepatitis B
      virus markers remained negative in the 10 unvaccinated hemophiliacs. No hepatitis
      A virus seroconversion occurred among 17 susceptible patients. B19 seroconversion
      (IgM) and B19 viremia were observed within 2 weeks of the first concentrate
      infusion in 8 of 15 susceptible patients, 5 of 11 treated with factor VIII and 3
      of 4 with factor IX concentrate. CONCLUSION: This prospective study indicates
      that very high temperatures applied to lyophilized concentrates appear to prevent
      the transmission of hepatitis A virus to hemophiliacs. However, B19 parvovirus
      still contaminates concentrates despite the use of this robust virucidal method.

PMID- 9149781
TI  - Transfusion: the first decade. Volume 5.

PMID- 9149782
TI  - Evidence-based medicine: the case for white cell reduction.

PMID- 9149783
TI  - A short history of transfusion medicine.

PMID- 9149784
TI  - Absence of the G871A mutation in A3 blood donors from Brazil.

PMID- 9149785
TI  - Anti-hepatitis C virus seroconversion in blood donors in Japan.

PMID- 9149786
TI  - Six years' experience testing organ donors for viral markers in France.

PMID- 9149787
TI  - Sweat gland carcinoma.

PMID- 9149788
TI  - Stump the experts. Desmoplastic melanoma with features of malignant spindled and
      epithelioid schwannoma.

PMID- 9149789
TI  - Comparison of the Q-switched alexandrite (755 nm) and Q-switched Nd:YAG (1064 nm)
      lasers in the treatment of benign melanocytic nevi.
AB  - BACKGROUND: A variety of pigmented lesions have been shown to be effectively
      treated with several pigment-specific laser systems currently available. There
      has been recent evidence to indicate that they may also be useful in the
      treatment of melanocytic nevi. OBJECTIVE: To compare the clinical and histologic
      effects of the Q-switched (QS) alexandrite (755 nm) and Nd:YAG (1064 nm) lasers
      in the treatment of melanocytic nevi. METHODS: Eighteen patients received three
      QS alexandrite and Nd:YAG laser treatments to either half of a large nevus or to
      two small adjacent nevi. Tissue biopsies were obtained for histologic
      examination. Degree of clinical improvement was determined by comparative
      photographic global assessment scores. The amount of melanin present within the
      nevi before and after laser irradiation was measured by reflectance spectrometry.
      RESULTS: Clinical global assessment scores were significantly reduced in all QS
      alexandrite and QS Nd:YAG laser-treated nevi after three treatments. Melanin
      reflectance spectrometry scores improved after the first laser treatment only.
      Histologically, a significant reduction in epidermal pigmentation and melanocytes
      were observed following laser irradiation with either QS system. CONCLUSION: Both
      the QS alexandrite and Nd:YAG laser systems resulted in significant improvement
      (lightening) of treated nevi. The QS alexandrite laser produced slightly better
      results using the parameters outlined.

PMID- 9149790
TI  - Carbon dioxide laser treatment vs subcutaneous resection of axillary osmidrosis.
AB  - BACKGROUND: Axillary osmidrosis is a distressing disorder characterized by
      unpleasant odor, profuse sweating, and occasional staining of clothes that may
      handicap those affected both socially and in the work place. Various types of
      surgical procedures have been developed for the treatment of axillary
      hyperhidrosis and osmidrosis. OBJECTIVE: Our purpose is to seek a more effective
      surgical procedure than preexisting various subcutaneous resection techniques for
      axillary osmidrosis. METHODS: After single transverse incision in the center of
      one axilla, undermining was performed from the incision edges to make a wide
      subcutaneous tunnel and then apocrine glands and subcutaneous fats were vaporized
      with a CO2 laser. Subcutaneous resection technique was performed on the opposite
      axilla in the same patient. A total of 20 patients have been evaluated for 4
      months to 1 year, with an average of 8 months. RESULTS: The results from commonly
      used surgical procedures can be improved upon by the use of the CO2 laser. The
      frequency of complications and the mean duration of suture removal were
      diminished on the laser-operated side. CONCLUSIONS: CO2 laser vaporization in
      osmidrosis produces significant patient-benefit during the postoperative course.
      We believe that this laser-assisted combined surgical procedure can be a viable
      option for the treatment of axillary hyperhidrosis and osmidrosis.

PMID- 9149791
TI  - Debulking of skin cancers with radio frequency before cryosurgery.
AB  - BACKGROUND: The purpose of prior debulking of skin cancers, by curettage, is to
      prepare the lesion for cryosurgical treatment. The main inconveniences of that
      procedure are the nearly always inevitable hemorrhage and the time necessary to
      control it. METHODS: We performed a study consisting of debulking skin tumors
      with radiosurgery, prior to cryosurgery, on a series of 38 patients (31 basal
      cell carcinomas, six squamous cell carcinomas, and one Bowen's disease), meeting
      the classical indications for cryotherapy. CONCLUSIONS: The advantages of the
      latter procedure over the traditional debulking by curettage are: the time needed
      to perform a biopsy, with easy and fast control of the bleeding, is considerably
      shortened; the whole procedure can be easily performed in one single session; the
      required surgical material also is greatly reduced; and the treatment can be
      performed on an out-patient regimen.

PMID- 9149792
TI  - Perineural and neural involvement in skin cancers.
AB  - BACKGROUND: Malignant skin tumors rarely spread along nerves. Complete resection
      of involved nerves is often unsuccessful. OBJECTIVE: In the treatment of tumors
      with perineural invasion, surgeons should accurately estimate the extent of
      distant spread. METHODS: We report six cases of skin cancers, including two basal
      cell carcinomas, two squamous cell carcinomas, and two neurotropic malignant
      melanomas, that invaded nerve or perineural spaces. RESULTS: In three of the
      cases, the tumors developed on the face and involved the infraorbital nerves or
      its branches. Two patients suffered from tumors on old burn scars of lower legs.
      Branches of posttibal nerves were involved in both cases. In the last case, tumor
      invasion of a branch of the greater occipital nerve was detected. CONCLUSION: The
      extent of surgical excision should include the area of skin supplied by the
      affected nerve, which must be resected in continuity.

PMID- 9149793
TI  - Malignant metastatic eccrine poroma. Proposal for a new therapeutic protocol.
AB  - BACKGROUND: Malignant metastatic eccrine poroma is a very rare cutaneous
      neoplasm, and consequently the references in the literature regarding the
      treatment of this tumor, known also as porocarcinoma, are very poor. OBJECTIVE:
      To call attention to a new therapeutic protocol in the treatment of metastatic
      porocarcinoma, as well as to underline an antineoplastic efficacy of vitamin A
      analogues. METHODS: The results are presented on the basis of the clinical case
      of a malignant eccrine poroma with metastatic regional lymph nodes. RESULTS: With
      our new chemotherapeutic protocol, arrest of the metastatic progression was
      achieved after 3 months and the remission was maintained until the 10th month of
      therapy. CONCLUSIONS: A new chemotherapy protocol consisting of isotretinoin and
      interferon alpha has confirmed the advantages of polychemotherapy in the
      treatment of metastatic malignant eccrine poroma. On the basis of the
      considerably long, although incomplete, remission with good drug tolerance in
      spite of the high doses used as well as the undoubtedly major antineoplastic
      strength of the latest generation of synthetic retinoids, we feel that these
      findings could be a good starting point for further experimental verifications of
      the therapy of this aggressive cutaneous neoplasm.

PMID- 9149794
TI  - Ambulatory phlebectomy of the foot. Review of 75 patients.
AB  - BACKGROUND: Review of 75 patients on whom ambulatory phlebectomy of the foot was
      performed as part of their varicose vein treatment. OBJECTIVE: To demonstrate
      that ambulatory phlebectomy is an effective modality of treatment for
      varicosities of the foot. METHODS: Ambulatory phlebectomies were performed on an
      outpatient basis under local anesthesia. RESULTS: The overall satisfactory result
      of ambulatory phlebectomy of the foot employed in the 75 patients in this study
      revealed the procedure to be very effective with few complications resulting and
      with a high degree of patient satisfaction. CONCLUSIONS: Ambulatory phlebectomy
      of the foot has proven to be a most satisfactory procedure for the treatment of
      varicose veins of the foot.

PMID- 9149795
TI  - Postsclerotherapy pigmentation. Is serum ferritin level an accurate indicator?
AB  - BACKGROUND: Human beings have suffered and sought treatment for disease of veins
      as early as the recordings of the old testament. The use of irritating sclerosing
      agents have been and are widely used today to treat varicose veins and
      telangiectasia. One of the most common and cosmetically significant side effects
      of sclerosing agents is varying degrees of hyperpigmentation. It has been
      reported that elevated serum ferritin level plays a role in this
      postsclerotherapy pigmentation. OBJECTIVE: To support or negate the possibility
      of a direct correlation between serum ferritin levels and pigmentation
      postsclerotherapy using for our investigation a patient with hemochromatosis.
      METHODS: A patient with hemochromatosis having a serum ferritin level of 1200 was
      treated for spider veins. Clinical and histologic studies were performed
      pretreatment and posttreatment. RESULTS: There was no clinically apparent
      hyperpigmentation noted on the patient after sclerotherapy over a 6-month period.
      Histology reports revealed macrophagic pigmentation both pretreatment and
      posttreatment. CONCLUSION: Our results do not confirm the theory that lab values
      of elevated serum ferritin correlate with pigmentation postsclerotherapy. Further
      study of the correlation between postsclerotic pigmentation and serum ferritin
      levels are needed. One would anticipate that if a true correlation existed, then
      an extreme case such as this would clearly support this theory.

PMID- 9149796
TI  - Durometer measurements of skin induration in venous disease.
AB  - BACKGROUND: The degree of skin induration (lipodermatosclerosis) around venous
      ulcers has prognostic significance; however, objective measurements are needed to
      assess the induration. The durometer, an engineering instrument used to measure
      the hardness of metals and plastic, has recently been adapted to assess skin
      induration. OBJECTIVE: The purpose of this study was to measure skin induration
      and its relationship to skin ulceration by the use of a durometer, and to
      determine the influence of edema, if any, on durometer measurements. METHODS: The
      degree of skin induration on the medial leg was determined in six sequential,
      nonselected patients with lipodermatosclerosis and leg ulcers, and in five normal
      volunteers by using a blinded observer's clinical score (0 = normal to 3 =
      maximal induration) and a hand-held Type 0 durometer. In addition, durometer
      readings in 14 patients with edema and eight control subjects were taken on the
      tibia, the dorsum of the foot, and behind the ankle. RESULTS: Durometer readings
      in patients with leg ulcers and lipodermatosclerosis diminished as one measured
      from the superior edge of the ulcer to the knee (r = 0.925). The higher the
      clinical skin score the higher were the durometer readings (P = 0.0062). The
      presence of edema did not influence durometer measurements. CONCLUSION: The
      durometer is an effective and reliable instrument for measuring the degree of
      skin induration in venous ulceration and its readings are not affected by edema.
      Ulcers occur in skin most affected by lipodermatosclerosis.

PMID- 9149797
TI  - Bilevel tumescent anesthetic infiltration for hair transplantation.
AB  - BACKGROUND: A dual level of tumescent anesthetic infiltration has been found to
      expedite hair graft or strip harvesting for hair transplantation, reducing
      bleeding, and increasing the exit angle of the hairs, thereby promoting increased
      survivorship of hair shafts and bulbs. OBJECTIVE: To acquaint the readership with
      this variation of anesthetic tumescent technique in hair transplantation.
      METHODS: Patients were utilized for this study during international teaching
      exchanges. Larger multiport infiltrators were used for the deep infiltration;
      smaller and more narrow infiltrators were used for the more superficial
      anesthetic administration. RESULTS: Subcutaneous compression and a bilevel
      vasoconstriction in both donor and recipient sites resulted in an increased
      upwardly angled exit angle of the hairs to be harvested, an increased separation
      of individual hair shafts, and reduced bleeding. Placement of the correct
      incisional angle of instruments inserted into the donor site was facilitated.
      CONCLUSION: Utilization of a bilevel tumescent anesthetic infiltration technique
      is a superior method of anesthesia for hair transplant harvesting and
      transplanting. Bleeding at both occipital donor and frontal recipient sites was
      negligible.

PMID- 9149798
TI  - Photothermal sclerosis of leg veins.

PMID- 9149799
TI  - The role of the infrared coagulator in tattoo removal.

PMID- 9149800
TI  - Total micrografting hair transplantation using a new hair implanter.

PMID- 9149802
TI  - Evaluation of solution temperature for local tumescent anesthesia.

PMID- 9149801
TI  - Botox concerns.

PMID- 9149803
TI  - Duplex-guided sclerotherapy.

PMID- 9149804
TI  - Use of a modified binding model for the investigation of affinity dependence on
      antibody concentration in immunoassay systems.
AB  - Affinity parameters obtained from standard calibration curves of
      radioimmunoassays (RIA) have been shown to decrease with increasing antibody
      concentration. A modified binding model was introduced in which not only binding
      capacity but also affinity was influenced by the antibody concentration. This
      allows a consistent overall description of RIA standards and titration curves for
      the characterization of binding assays.

PMID- 9149805
TI  - Use of the acute phase serum amyloid A2 (SAA2) gene promoter in the analysis of
      pro- and anti-inflammatory mediators: differential kinetics of SAA2 promoter
      induction by IL-1 beta and TNF-alpha compared to IL-6.
AB  - A cytokine responsive construct, pGL2-SAA2pt, was generated by cloning the acute
      phase promoter of human serum amyloid A2 (SAA2) upstream of a luciferase reporter
      gene. The construct responds to the inflammatory mediators MoCM, IL-1 beta, TNF
      alpha, and IL-6 in a manner that closely mimics the response of the endogenous
      SAA2 gene to such stimuli: i.e. single treatments induce transcriptional
      activation by IL-1 beta and TNF-alpha to a greater extent than by IL-6 at 12-24
      h. However, timecourse experiments show that the kinetics of induction generated
      by IL-1 beta and TNF-alpha are quite distinct from IL-6, IL-6 having a much
      greater effect at 3-6 h. IL-1 beta and TNF-alpha synergize with IL-6 to give a 10
      fold increase in transcriptional readout over single cytokine treatments. The
      kinetics of this synergistic response resembles that generated by IL-6 alone. The
      IL-1 receptor antagonist, hIL-1ra, can specifically block the IL-1 beta driven
      transcriptional activation of pGL2-SAA2pt, but not that driven by TNF-alpha or IL
      6. Furthermore, in synergistic cytokine combinations, it blocks only the IL-1
      beta driven component indicating that the effect is biological and not
      attributable to toxicity. Consequently assays utilizing pGL2-SAA2pt will be
      useful both for the investigation of the kinetics of inflammatory signalling in a
      cytokine specific manner, and for the evaluation of the pro- and anti
      inflammatory properties of novel natural and synthetic molecules.

PMID- 9149806
TI  - Baculovirus cDNA libraries for expression cloning of genes encoding cell-surface
      antigens.
AB  - We describe a method for the production of baculovirus-based cDNA libraries. By
      staining with monoclonal antibodies, single positive cells can be sorted and the
      virus encoding for the surface epitope can be isolated by limiting dilution. We
      have used this method to isolate cDNAs encoding several cell-surface antigens.

PMID- 9149807
TI  - The use of computer-assisted video image analysis for the quantification of CD8+
      T lymphocytes producing tumor necrosis factor alpha spots in response to peptide
      antigens.
AB  - Enzyme-linked immunospot (ELISPOT) analysis is a sensitive technique for the
      detection and quantification of single T lymphocytes forming cytokine spots after
      antigen contact in vitro. Herein computer-assisted video image analysis (CVIA)
      was applied to automatically determine the number and size of tumor necrosis
      factor alpha (TNF-alpha) spots formed by single blood-derived CD8+ T cells after
      contact with peptide-loaded target cells. With CVIA and TNF-alpha ELISPOT
      analysis we quantified CD8+ T cells responsive to HLA-A2.1-binding tyrosinase and
      influenza matrix peptides in healthy donors. We followed the course of the virus
      specific T cell response in two HLA-A2-positive patients with reactivation of
      latent cytomegalovirus (CMV) infection during immunosuppressive therapy. The test
      proved sufficiently sensitive to detect in the blood of both patients a temporary
      expansion of CD8+ T lymphocytes reactive with a known immunogenic HLA-A2.1
      binding peptide from glycoprotein B of CMV. Reactivity to peptide antigens was
      not only reflected by numeric increases of spot formation, but also by the
      appearance of larger spot areas, presumably formed by strongly peptide-reactive
      CD8+ T cells. We conclude that the combined use of the TNF-alpha ELISPOT assay
      and CVIA allows reliable monitoring of the T cell responsiveness to peptide
      antigens in peripheral blood.

PMID- 9149808
TI  - The Fab region of IgG2 human myeloma proteins does not bear the streptococcal
      protein G-specific determinant.
AB  - Seven out of ten Fab (F(ab')2/Fab') preparations derived from purified human
      myeloma IgG showed a substantial binding to protein G-Sepharose. Subclass
      analysis revealed that the 7 protein G-reactive Fabs included 3 IgG1, 2 IgG3 and
      2 IgG4 Fabs, whereas the remaining 3 which were not adsorbed were IgG2 Fab.
      Incubation of protein G-Sepharose with non-saturating amounts of 4 Fab
      preparations, representative of all IgG subclasses, showed that gamma 1, gamma 3
      and gamma 4 Fabs adsorbed from 26 to 28.3%, whereas 80% of gamma 2 Fab was left
      in the supernatant after adsorption. These results indicate that human IgG2 lack
      PG-specific Fab-associated reactive site(s).

PMID- 9149809
TI  - An ELISA for selectins based on binding to a physiological ligand.
AB  - Members of the selectin family of adhesion receptors, consisting of L-, P- and E
      selectin, mediate the initial interaction between leukocytes and endothelium
      during leukocyte trafficking from the blood into tissue sites. These receptors
      have attracted great attention in recent years due to their participation in a
      number of acute and chronic inflammatory diseases. We describe here a new ELISA
      that measures the binding between selectin-IgG chimeras and a physiological
      ligand for L-selectin and can be used to screen selectin inhibitors. The ligand
      used is a mucin-like glycoprotein known as GlyCAM-1, which is derived from high
      endothelial venules in secondary lymphoid organs. We demonstrate binding of all
      three selectins to GlyCAM-1 and demonstrate that the binding interactions satisfy
      a number of important criteria. The advantage of this ELISA over previous assays
      is that a macromolecular physiological ligand is employed, rather than a
      fortuitous or simplified carbohydrate ligand. Thus, the protein-carbohydrate
      interactions, as well as other interactions contributing to ligand recognition,
      can be investigated. The assay is suitable for high-throughout screening of
      compounds and may find use in the identification of selectin antagonists with
      anti-inflammatory potential.

PMID- 9149810
TI  - An improved, ultrasensitive method for the detection of IgM oligoclonal bands in
      cerebrospinal fluid.
AB  - A new, 10-fold more sensitive method, based on an improved immunofixation
      technique, has been devised to detect oligoclonal IgM bands in unconcentrated
      cerebrospinal fluid (CSF). Using agarose gel electrophoresis, 5 microliters of an
      unconcentrated sample containing oligoclonal bands was separated and blotted on
      to a polyvinyldifluoride membrane. To visualise the pattern, a peroxidase
      labelled double-antibody technique was used. No prior concentration of CSF was
      needed and the process required only 5 h. The technique may prove very useful in
      diagnosing an early intrathecal immune response.

PMID- 9149811
TI  - Flow-cytometric screening for the modulation of receptor-mediated endocytosis in
      human dendritic cells: implications for the development of an in vitro technique
      for predictive testing of contact sensitizers.
AB  - The aim of this study was to explore the usefulness of human blood dendritic
      cells (DC) in the development of an in vitro model for predictive testing of
      contact sensitizers. A method was established to monitor the influence of
      chemicals on the intracellular targeting of antibody-crosslinked MHC class II
      molecules after their uptake by human DC. Using a three-colour flow-cytometric
      technique, freshly prepared DC were distinguished from other MHC class II-bearing
      cell types such as B-cells and monocytes in unseparated mononuclear cell
      suspensions of healthy volunteers. The assay is based on the pH-sensitivity of
      internalized fluorescein-coupled MHC class II specific antibodies. Quenching of
      fluorescence intensity due to internalization into acidic intracellular
      compartments was observed with untreated DC whereas internalization into less
      acidic structures following stimulation with strong contact sensitizers ensured
      that the fluorescence intensity was conserved. The usefulness of this approach
      for predictive testing of the preservatives MI/MCI, imidazolidinyl urea, methyl-4
      hydroxy-benzoate and 2-phenoxyethanol in comparison to the strong allergen DNFB
      and the irritants sodium lauryl sulphate and dithranol was explored. Whereas low
      concentrations of MI/MCI resembled the strong allergen DNFB, high concentrations
      of imidazolidinyl urea were required for a moderate response. Methyl-4-hydroxy
      benzoate and 2-phenoxyethanol as well as the irritants SLS and dithranol failed
      to induce a significant effect in this assay. The non-responsiveness to the
      latter compounds reflected their minor or absent capacity to induce contact
      hypersensitivity in humans, whereas DNFB, MI/MCI and imidazolidinyl urea are well
      established contact sensitizers. These data suggest that the capacity of a
      chemical to modulate endocytotic mechanisms in dendritic cells in vitro seems to
      reflect the probability of that substance acting as a hapten in vivo.

PMID- 9149812
TI  - A rapid method for semiquantitative analysis of the human V beta-repertoire using
      TaqManR PCR.
AB  - Analysis of the V beta-repertoire of antigen-reactive T cell populations can be
      approached using either flow-cytometry or PCR-based techniques. While the former
      method requires a complete set of V beta-specific monoclonal antibodies (mAbs)
      and large cell numbers for analysis, the latter is both time-consuming and labour
      intensive. To circumvent the drawbacks of both these methods we have employed the
      recently developed technique of TaqManR PCR to analyse the V beta-usage of human
      T cell populations. TaqManR PCR is based on the 5'-->3' nuclease activity of Taq
      polymerase. During PCR amplification an internal oligonucleotide probe, that is
      labelled with a fluorescent reporter and a quencher dye, is cleaved by Taq
      polymerase. After cleavage, quenching of the reporter dye is lost and reporter
      fluorescence can be detected with a fluorescence plate reader. Using one C beta
      specific fluorogenic probe and a panel of V beta-specific primers, we show that
      fluorescence-detected amplification of TCR beta cDNA is V beta-specific and
      linear within a 2-3-log range of template concentration. The sensitivity of
      TaqManR PCR is comparable to conventional detection of PCR-products by agarose
      gel staining, while processing time is reduced. Furthermore, superantigen-induced
      skewing of the V beta-repertoire of human T cells is readily detected with this
      method. Thus TaqManR PCR is a reliable and fast method for semiquantitative
      analysis of the V beta-repertoire of human T cell populations.

PMID- 9149813
TI  - Combined immunomagnetic cell sorting and ELISPOT assay for the phenotypic
      characterization of specific antibody-forming cells.
AB  - A combination of immunomagnetic cell sorting and ELISPOT techniques has been
      evaluated to permit enrichment and characterization of antibody-secreting cells
      (ASC). Cell suspensions containing putative ASC were first incubated with
      magnetic microbeads coated with antibodies specific for a given cell surface
      marker. After separation of bead-cell clusters and free cells, the resulting cell
      populations were examined for the presence of ASC by an ELISPOT assay. As a model
      system, the expression of selected cell differentiation markers by human
      circulating ASC has been evaluated after parenteral tetanus vaccination and
      during the course of a Leishmania infection. Prior treatment of blood MNC with
      beads coated with antibodies to CD38, HLA-DR or CD19 permitted the isolation of
      virtually all blood ASC. Further, prior immunomagnetic removal of T (CD2+) cells
      from blood MNC, followed by isolation of CD38+ cells facilitated the detection of
      Leishmania major-specific ASC in all six patients examined, whereas parasite
      specific ASC among unfractionated blood mononuclear cells could only be detected
      in 3 out of these six patients. Simple and rapid, this approach provides not only
      accurate estimates of the frequency of ASC within a given B cell population or
      subpopulation, but can also efficiently enrich functional ASC from complex cell
      suspensions and thus should be particularly useful in situations where ASC are
      present at low frequencies.

PMID- 9149814
TI  - Detection of PNA/DNA hybrid molecules by antibody Fab fragments isolated from a
      phage display library.

PMID- 9149815
TI  - Stability of a perturbed Leslie model.
AB  - A small perturbation introduced in the stochastic Leslie model leads to a long
      lived stable population in a region or parameter space where the stochastic model
      predicts the demise of the population. This somewhat surprising result is
      understood by considering a related model with a density-dependent sex ratio
      which exhibits similar features.

PMID- 9149816
TI  - The evolution of genomic imprinting: two modifier-locus models.
AB  - We present two autosomal two-locus models in which the primary locus, A, may be
      imprinted according to the alleles present at the second, modifier locus, M. In
      the first model, the modifier is cis-acting, which assumes that imprinting occurs
      late in gametogenesis: whether or not A is imprinted depends only on the M allele
      in the (unfertilized) egg. We examine three cases in which polymorphism at A is
      maintained by a mutation-selection balance or heterozygote advantage. We show
      that a newly arising modifier allele without direct fitness effects can increase
      at a rate only of the order of the mutation rate at the A locus. This result
      mirrors that found in two-locus models of the evolution of dominance modifiers.
      Modifiers that also alter fitnesses, however, may spread quickly. In the second
      model, a monomorphic primary locus, A, is imprinted according to the mother's
      genotype at the second, diallelic modifier locus, M. The model is therefore trans
      acting, which assumes imprinting occurs early in gametogenesis: whether or not A
      is imprinted depends on both of the mother's M genes. We show that a newly
      arising modifier will increase in frequency via selection if either imprinting is
      advantageous and the modifier increases the proportion of imprinted gametes or
      imprinting is disadvantageous and the proportion is decreased. Both of these
      factors-the selective effect of imprinting and the proportion of gametes
      imprinted-affect the rate of modifier evolution. Selectively maintained
      polymorphism at the modifier locus is unlikely unless the alleles interact in a
      nonadditive fashion.

PMID- 9149817
TI  - The promise of multimedia in otology.

PMID- 9149818
TI  - News from the National Institute on Deafness and Other Communication Disorders.

PMID- 9149819
TI  - Minor works of Carlo Mondini: the anatomical section of a boy born deaf.

PMID- 9149820
TI  - Postinflammatory medial canal fibrosis.
AB  - OBJECTIVE: Our objective was to describe the diagnosis and treatment of
      postinflammatory medial canal fibrosis by reviewing a large series. STUDY DESIGN:
      This study was conducted via retrospective chart review. SETTING: This study was
      conducted at a tertiary otologic referral center. PATIENTS: The 24 patients had a
      clinical diagnosis of postinflammatory medial canal stenosis. Only one of the 16
      females and eight males was under 18 years of age, and the mean age for the group
      was 50.5 years (range 5-78). fourteen patients had bilateral diseases.
      INTERVENTION: Surgical therapy was performed in 14 ears (11 patients), and
      medical therapy was performed in nine. RESULTS: For patients undergoing surgical
      treatment, mean pure-tone average hearing threshold improved from 37 dB
      preoperatively to 26 dB postoperatively. The air-bone gap improved from 24 dB to
      15 dB. There were three recurrences of disease in the surgery group. CONCLUSION:
      Postinflammatory medial canal stenosis is a rare disorder resulting from chronic
      external otitis that required surgical intervention to correct the resulting
      conductive hearing loss.

PMID- 9149821
TI  - Development of tympanosclerosis: can predicting factors be identified?
AB  - HYPOTHESIS: The etiological hypothesis is that there might be factors triggering
      an immunological chain reaction that eventually leads to tympanosclerosis
      formation. BACKGROUND: Tympanosclerosis is a condition leading to a calcification
      process in the middle ear and, occasionally, also to the lining of the inner ear.
      This sometimes leads to hearing loss due to fixation of the middle ear ossicles.
      In severe cases. deafness may occur as a result of the inner ear impairment.
      Surgery is the treatment offered, often with poor long-term results, and,
      alternatively, prescription of hearing aids. Some patients develop
      tympanosclerosis after mild inflammatory otitis media processes whereas some heal
      without tympanosclerosis after more aggressive infections. This difference may be
      due to individual variations in the inflammatory response. The biological
      mechanism of calcification in tympanosclerosis is probably similar to that
      occurring in other calcifying tissues due to diseases. METHODS: The present
      investigation was performed to develop methods for immunohistochemical analyses
      of this delicate tissue consisting of both hard bone and the very thin tympanic
      membrane. Sprague-Dawley rats were inoculated with a suspension of Streptococcus
      pneumoniae, type 3, into the middle ear and sacrificed after 1 week up to 6
      months. A new technique was elaborated where the whole specimen was prefixed
      briefly and then en bloc incubated with the primary antibodies and after that
      decalcified in edetic acid (EDTA). Primary antibodies against macrophages were
      used for the immunohistochemical staining. RESULTS: Acute otitis media was
      successfully induced in the rats and myringosclerosis was seen in 30% of the
      animals, often localized close to the bony frame where macrophages could also be
      detected. CONCLUSIONS: Acute otitis media and myringosclerosis were introduced in
      the animals. Conventional immunological techniques were tested on this delicate
      tissue. A new method for immunohistochemical staining was elaborated in which
      specimens were stained en bloc before decalcification and sectioning were
      performed. Expression of macrophages was demonstrated in the tympanic membrane.

PMID- 9149822
TI  - Clinical importance of the Korner's septum.
AB  - OBJECTIVE: To evaluate the clinical importance of the petrosquamosal lamina
      (Korner's septum [KS]), which is not only a bony plate dividing the mastoid cells
      at the level of antrum, but is also a lamina starting from the posterior aspect
      of the glenoid fossa that extends above the middle ear cavity and courses in an
      inferior direction lateral to the facial canal and proceeds to the mastoid apex.
      STUDY DESIGN AND SETTING: A retrospective review of 688 mastoidectomies performed
      in University Hospital from 1987 to 1992. PATIENTS: The study group consisted of
      389 males and 299 females (mean age 30.85 +/- 12.80, the youngest being 8 and the
      oldest being 67 years of age). MAIN OUTCOME MEASURES: The main outcome measures
      were the prevalence of KS encountered during mastoidectomies and comparison of
      prevalence of retraction pockets (RPs) or retraction and/or adhesion of the whole
      tympanic membrane (R/A-TM) between ears with KS and without KS. RESULTS: The
      prevalence of KS was 30.4% among the ears with RP or R/A-TM, 6.58% in normal
      ears, and 17.4% in ears with chronic otitis media without RP or R/A-TM.
      CONCLUSIONS: KS is an important anatomic handicap predisposing the individual to
      chronic otitis media, particularly when it is characterized by attic retraction
      pockets and cholesteatoma, and adhesive otitis media, because KS contributes to
      attic blockage. This statement is in accordance with the original articles
      written by Cheatle (1910, 1923) and Williams (1966), and recently published data
      related to supratubal recess and the cog (Tono et al., 1996).

PMID- 9149823
TI  - Tensor fold and anterior epitympanum.
AB  - HYPOTHESIS: The aim of this study was to investigate the anatomy and pathology of
      the anterior epitympanum and of the tensor fold. BACKGROUND: Early studies
      reported data that are primarily still relevant, but contemporary reports present
      conflicting data, including several erroneous concepts. METHODS: Fifty-one
      temporal bones were dissected, and the anatomic details were photographed in 42
      normal and nine infected bones. Histology was documented from seven serially
      sectioned bones, five normal and two infected. RESULTS: The tensor fold formed
      the frontal wall of the anterior epitympanum between tensor tendon and attic bony
      wall, the anterior insertion consisting of composite connective and fatty tissue
      with some bone trabeculae. The transverse crest was posterior to it and extended
      from the anterior tympanic spine to the facial canal. The tensor fold angle in
      78% of the specimens was between 45 degrees and 80 degrees, seldom horizontal,
      and the size of the supratubal recess (or space) increased as the fold angle
      increased. In 14 ears (27%) the fold had a membrane defect connecting the two
      spaces. Blockade of the tympanic isthmus caused inflammatory obliteration of the
      anterior epitympanum when the tensor fold was intact. CONCLUSIONS: The anterior
      epitympanum, a closed space around the anterior half of the head of the malleus,
      is normally closed by an intact tensor fold, but about one fourth of ears may
      show membrane defects. Aeration occurs via the tympanic isthmus through a
      constriction formed by the head of the malleus with the medial attic wall. In
      surgery for ears with epitympanal pathology, incus transposition should be
      combined with resection of the thin portion of the tensor fold for safeguarding
      permanent attic aeration.

PMID- 9149824
TI  - Structural variations of the supratubal recess: the anterior epitympanic space.
AB  - HYPOTHESIS: We sought to classify the shape and structure of the anterior
      epitympanic space (AES) and produce measurements of its dimensions together with
      its relationships with the facial nerve and geniculate ganglion. BACKGROUND: The
      AES is limited by the middle cranial fossa superiorly, zygoma root anteriorly,
      cog posteriorly, chorda tympani laterally, facial nerve medially, and tensor
      tympanic semicanal inferiorly. METHODS: The AES was examined in 30 human temporal
      bones using two different methods. Twenty bones were cut vertically and a
      modified radical mastoidectomy was performed in the other 10 bones. RESULTS: The
      AES showed two types in the vertically cut bones according to its shape and
      structure. Type I, found in 17 (85%) of the bones, showed two cavities that were
      separated by a bony landmark and the tensor tympanic fold. The name "supratubal
      ridge" is suggested for this bony landmark. In type II, which was seen in three
      (15%) of the bones, there was only one cavity. In the mastoidectomy group, again
      two types of AES were found: eight (80%) were type I and two (20%) were found to
      be type II. If we combine these findings with the vertically cut bones, we find
      that 25 (83.3%) possess an AES type I, whereas five (16.7%) are type II.
      CONCLUSIONS: These variations in the structure of the AES and its close
      relationships with a number of vital structures such as the facial nerve,
      cochlea, and middle fossa dura must be taken into account during the surgical
      management of middle ear disease.

PMID- 9149825
TI  - A new adhesive bonding material for the cementation of implantable devices in
      otologic surgery.
AB  - BACKGROUND: Presently, there are no U.S. Food and Drug Administration (FDA)
      approved adhesive bone cements for the surgical fixation of prosthetic materials
      in the middle ear. A promising new cement, 4-META/MMA-TBB opaque resin, has shown
      remarkable adhesive properties as a bone cement in vivo. The cement is composed
      of 4-methacryloyloxyethyl trimellitate anhydride (4-META) and methyl methacrylate
      (MMA) as monomers and tri-n-butyl borane (TBB) as an initiator. METHODS: An
      electromagnetic semiimplantable hearing device presently under development was
      implanted into the middle ear of six cats using 4-META/MMA-TBB resin to cement a
      titanium-encased magnet to the incus. The animals were subsequently killed (at a
      mean of 9.6 months) to assess the (temporal bones and specifically the magnet
      incus complex in each animal. RESULTS: The titanium-encapsulated magnet was
      firmly adherent to all incuses without any failure of the cement-bone interface.
      Histopathologic examination of the implanted temporal bones demonstrated lack of
      middle ear inflammation. Transmission electron microscopy of the incuses
      demonstrated a unique "hybrid layer" in the bone-side subsurface of the bone
      cement interface that elucidates the mechanism of interfacial adhesion.
      CONCLUSIONS: Our investigation highlights the special biomechanical properties as
      well as the biocompatibility of 4-META/ MMA-TBB resin that make it an attractive
      bone-bonding agent for use in otologic surgery, including its potential
      usefulness during ossicular reconstruction.

PMID- 9149826
TI  - Effect of magnetic resonance imaging on a new electromagnetic implantable middle
      ear hearing device.
AB  - OBJECTIVE: A 1.5-T magnetic resonance imager has been shown to be contraindicated
      for use in patients with pacemakers, cochlear implants, and neurostimulators. Our
      semi-implantable middle ear device uses a new adhesive bone cement. 4-META/MMA
      TBB, for cementation of a 29-mg titanium-encased neodymium-iron-boron (NdFeB)
      magnet to the incus. METHODS: Five NdFeB magnets and four solid titanium
      cylinders were cemented onto the incus of five preserved human temporal bones and
      two cadaver heads. They were all inserted into a magnetic resonance imager and
      evaluated for possible disruption. RESULTS: Owing to the magnetic torque, the
      three magnets on the temporal bone were disrupted from the incus. The two
      cylinders on the temporal bones and the two cylinders and two magnets on the
      whole heads were not affected. The magnetic resonance imaging field did not
      affect the coercive force of the NdFeB magnets. CONCLUSION: The large torque
      produced by a magnetic resonance imager may disrupt the magnet-cement and cement
      incus interfaces, causing dislodgement. We postulate that patients with
      implantable magnets on the incus should not undergo magnetic resonance imaging
      testing.

PMID- 9149827
TI  - Audiological findings of sensorineural deafness associated with a mutation in the
      mitochondrial DNA.
AB  - OBJECTIVE: The aim of this study was to investigate audiologic features and the
      lesion site of sensorineural deafness with mitochondrial DNA mutation at position
      3243. STUDY DESIGN: Case review. SETTING: The study was conducted at the Kochi
      Medical School. PATIENTS: A case of sensorineural deafness in a patient who had a
      mitochondrial DNA mutation was presented. The incidence of deafness and diabetes
      mellitus (DM) was very high in the patient's family, but she did not have DM.
      MAIN OUTCOME MEASURES: The patient's mitochondrial DNA was examined. Furthermore,
      the pure-tone audiogram, the Bekesy audiogram, an auditory brain stem response,
      and the electrocochleogram were analyzed. RESULTS: The patient's mitochondrial
      DNA had a point mutation at codon 3243 (A-->G). The pure-tone audiogram showed
      moderate sensorineural deafness. An auditory brain stem response showed normal
      latencies. The electrocochleogram showed an enhanced negative summating
      potential. CONCLUSIONS: It was speculated that the lesion site of the auditory
      system was the inner ear. The possible sites in the inner ear were hair cells,
      the stria vascularis, and the endolymphatic sac.

PMID- 9149828
TI  - Facial nerve stimulation after Nucleus 22-channel cochlear implantation.
AB  - OBJECTIVE: To review the clinical features, radiographic findings, and
      programming strategies used in our population of patients who developed facial
      nerve stimulation after cochlear implantation. STUDY DESIGN AND SETTING: Patients
      referred to our nonprofit, outpatient facility were studied prospectively.
      PATIENTS: The study consisted of 14 patients with facial nerve stimulation after
      placement of the Nucleus 22-channel cochlear implant. INTERVENTIONS: Records were
      reviewed retrospectively, and patients were studied with three-dimensional
      computed tomographic scanning techniques. Electrical testing was performed, and
      various cochlear implant programming strategies were evaluated. MAIN OUTCOME
      MEASURES: Important clinical features were reviewed. The radiographic and
      anatomical relationships of the facial nerve to the cochlea were evaluated, and
      the programming strategies used to effectively control facial nerve stimulation
      were reviewed. RESULTS: Prevalence of facial nerve stimulation in our population
      was 7%. The most common cause was otosclerosis. Anatomical data confirmed the
      close proximity of the basal turn of the cochlea and the labyrinthine segment of
      the facial nerve. There was a high correlation between the electrodes causing
      symptoms and those found radiographically to be closest to the labyrinthine
      segment of the facial nerve. We were able to control facial nerve stimulation in
      all patients through programming mode changes. CONCLUSIONS: Otosclerosis appears
      to be a risk factor for developing facial nerve stimulation after cochlear
      implantation, and the site of stimulation appears to be the labyrinthine segment
      of the facial nerve. Familiarity with more elaborate programming techniques is
      critical to managing patients with this complication.

PMID- 9149829
TI  - Open-set speech perception in congenitally deaf children using cochlear implants.
AB  - OBJECTIVE: To assess and document the development of open-set speech recognition
      in congenitally deaf children implanted with the Nucleus multichannel cochlear
      prosthesis at < 5 years of age. STUDY DESIGN: The study group consisted of 38
      consecutively chosen children in whom the decision to proceed with implantation
      had already been made. PATIENTS AND SETTING: Congenitally profoundly deaf
      children were implanted with the Nucleus multichannel cochlear implant at < 5
      years of age and followed at NYU Medical Center for a period of 1-5 years. MAIN
      OUTCOME MEASURES: Open-set speech perception was evaluated preoperatively and
      postoperatively using the following: the Glendonald Auditory Screening Procedure
      (GASP) word subset, the GASP sentence subtest, Phonetically Balanced Kindergarten
      monosyllabic word lists, Common Phrases test, Multisyllabic Lexical Neighborhood
      test, and Lexical Neighborhood test. RESULTS: Correlation coefficients were
      calculated between scores at each interval and age at implantation; one-way
      analyses of variance were performed independently. Results showed that all
      subjects had significant open-set speech recognition at the time of the last
      postoperative evaluation. Thirty-seven of the children use oral language as their
      sole means of communication. CONCLUSIONS: Multichannel cochlear implants provide
      significant and usable open-set speech perception in congenitally deaf children
      given implants at < 5 years of age.

PMID- 9149830
TI  - Efficacy of antimigrainous therapy in the treatment of migraine-associated
      dizziness.
AB  - OBJECTIVE: To assess the effects of antimigrainous therapy on migraine-associated
      dizziness/vertigo. We hypothesized that a medication's ability to ameliorate
      dizziness/vertigo in this patient population would be directly correlated with
      its efficacy in improving headache symptoms. STUDY DESIGN: Patient survey.
      SETTING: Patients were entered into the study from the University of California,
      San Diego (UCSD) Headache Clinic, a tertiary care referral clinic. PATIENTS: All
      patients presenting to the UCSD headache clinic are entered into its
      comprehensive database. Patients who identified dizziness or vertigo as symptoms
      were entered into this study and were surveyed. MAIN OUTCOME MEASURES: Patients
      were surveyed as to the nature of their vestibular symptoms, and the therapeutic
      response of these symptoms and their headaches to various antimigrainous
      medications. Patients were asked to rank therapeutic efficacy utilizing a numeric
      scale. These results were then subjected to statistical analysis (Spearman rank
      correlation) to identify any correlation between the efficacies of the
      medications in improving headache and dizziness/vertigo. RESULTS: The efficacy of
      the medications in treating migraine-associated dizziness was directly correlated
      with their ability to alleviate headaches. CONCLUSION: We conclude that
      antimigrainous therapy may offer specific treatment to patients suffering from
      the spectrum of migraine-associated vestibular disorders. This would include the
      entity known alternately as vestibular Meniere's disease, benign recurrent
      vertigo, or recurrent vestibulopathy. Given the potential benefits that may be
      derived from this therapy, clinicians should be sensitive to a history of
      migraines in patients complaining of dizziness, particularly in those complaining
      of recurrent episodic vertigo.

PMID- 9149831
TI  - Sound-evoked activity in primary afferent neurons of a mammalian vestibular
      system.
AB  - HYPOTHESIS: Some primary vestibular afferents in the cat respond to sound at
      moderately intense sound levels. BACKGROUND: In fish and amphibians, parts of the
      vestibular apparatus are involved in audition. The possibility was explored that
      the vestibular system in mammals is also acoustically responsive. METHODS:
      Microelectrodes were used to record from single afferent fibers in the inferior
      vestibular nerve of the cat; some acoustically responsive fibers were labeled
      intracellularly with biocytin. RESULTS: Vestibular afferents with regular
      spontaneous activity were unresponsive to sound, whereas a sizable fraction of
      vestibular afferents with irregular activity were acoustically responsive.
      Labeling experiments demonstrated that acoustically responsive afferents
      innervate the saccule, have cell bodies in Scarpa's ganglion, and project to
      central regions both inside and outside the traditional boundaries of the
      vestibular nuclei. Acoustically responsive vestibular afferents responded to
      sound with shorter latencies than cochlear afferents but had higher thresholds (>
      90 dB sound pressure level) and responded only in the range 0.1-3.0 kHz. In
      contrast to cochlear afferents, efferent stimulation excited background activity
      and proportionately increased sound-evoked responses in these vestibular
      afferents, that is, there was centrally mediated enhancement of gain (gain =
      spike-rate/motion). CONCLUSIONS: The evolutionary conservation of a saccular
      auditory pathway in mammals suggests that it confers survival advantages. Recent
      evidence suggests that acoustically responsive saccular afferents trigger
      acoustic reflexes of the sternocleidomastoid muscle, and hence measurement of
      such reflexes may provide a relatively simple test for saccular dysfunction.

PMID- 9149832
TI  - Evaluation of the nonorganic hearing loss suspect.
AB  - OBJECTIVE: To examine the utility of distortion-product otoacoustic emissions
      (DPOAEs) in the assessment of the nonorganic suspect because DPOAE analysis
      constitutes an objective test of hair-cell function that yields audiometriclike
      data. STUDY DESIGN: Retrospective study of clinical findings. SETTING: Audiology
      outpatient clinic of our university's medical center. PATIENTS: The study cohort
      comprised 30 patients who presented with a profile of suspicion for nonorganic
      hearing loss. Most cases were found, with the aid of DPOAE testing, to be
      nonorganic or to have nonorganic overlays to organic hearing loss. INTERVENTIONS:
      Interventions were diagnostic only. MAIN OUTCOME MEASURES: Observed audiometric
      findings and changes thereof. RESULTS: Statistically significant decreases in
      thresholds occurred in subgroups of those cases deemed to be truly nonorganic in
      origin. CONCLUSIONS: Especially considering test efficiency, the results support
      the inclusion of DPOAE analysis in the diagnostic management of the suspect
      nonorganic patient.

PMID- 9149833
TI  - Perspectives on a state enacted hearing screening assessment program in the
      newborn population.
AB  - OBJECTIVE: A review of the early performance of Ohio's statewide infant hearing
      screening program was performed to provide insight as to the impact of the
      current medical and socioeconomic climate on its implementation. BACKGROUND: In
      March 1988, the State of Ohio enacted a law that required universal screening of
      newborn children for hearing loss through a program known as the Infant Hearing
      Screening and Assessment Program (IHSAP). The program design consisted of a
      universally applied high-risk questionnaire followed by a screening auditory
      assessment for those who fail. Although the value of such a program engendered
      little early public debate, the institution of such a program represented a
      significant challenge from a public health perspective. STUDY DESIGN: The program
      performance was analyzed using data from the index population of 160,000 live
      births per annum and hospital surveys. RESULTS: The questionnaires were found to
      be failing twice the number of newborns as originally projected, whereas
      completion rates and compliance were excellent. The assessment arm was plagued
      with poor compliance rates and limited resources. Lack of resources for effective
      data management has prevented an accurate evaluation of the program's sensitivity
      and specificity. CONCLUSION: IHSAP performance is being hampered by poor
      assessment follow-up and resource limitations, both in terms of screening
      equipment and habilitative follow-up services for infants identified as hearing
      impaired. The reasons for these problems are discussed in relation to existing
      legislative guidelines and medicoeconomic realities.

PMID- 9149835
TI  - Endoscopically assisted prevention of cerebrospinal fluid leak in suboccipital
      acoustic neuroma surgery.
AB  - HYPOTHESIS: The purpose of this prospective study was to determine if direct
      inspection of air cells using endoscopy could reduce the occurrence of
      cerebrospinal fluid (CSF) leak in suboccipital acoustic neuroma surgery.
      BACKGROUND: Cerebrospinal fluid leak remains one of the most common complications
      after acoustic neuroma surgery. The suboccipital approach for excision of
      acoustic neuromas has been used increasingly since gadolinium-enhanced magnetic
      resonance imaging has improved the ability to diagnose smaller tumors.
      Suboccipital approaches are reported to have CSF leak rates of as high as 27%
      with an average rate of 12%, most presenting as rhinorrhea. Ideally, this
      complication could be avoided by careful closure of all air cells exposed during
      the approach, especially those commonly found in the posterior wall of the
      internal auditory canal and in the retrosigmoid area. Packing these cells with a
      variety of materials has been done but often indirectly, as visualization of all
      cells by the conventional operating microscopes may not be possible. Failure to
      recognize patent cells because of limited visualization may be an important cause
      of postoperative CSF leak. METHODS: This study compared CSF rhinorrhea rates of
      38 consecutive suboccipital acoustic neuroma operations, in which conventional
      techniques were used to pack the temporal bone defect around the internal
      auditory canal, with the succeeding 24 consecutive operations, in which
      endoscopes were used to visualize all exposed air cells directly. After locating
      all patent air cells endoscopically, they were specifically sealed with bone wax,
      and then a small fat graft harvested from the wound margin was used to fill the
      remaining defect. RESULTS: Postoperative CSF rhinorrhea occurred in 7 of 38
      (18.4%) operations in which no endoscopic technique was used and in 0 of 24
      operations in which endoscopes were used. CONCLUSIONS: The use of endoscopes to
      visualize the temporal bone air cells that cannot be directly observed otherwise
      appears to reduce the incidence of postoperative CSF leak in suboccipital
      acoustic neuroma surgery.

PMID- 9149834
TI  - Rare lesions of the posterior fossa with initial retrocochlear auditory and
      vestibular complaints.
AB  - OBJECTIVE: To catalog a series of rare lesions of the posterior fossa that
      appeared with unusual initial retrocochlear symptoms and signs and to make the
      reader more aware of these unusual lesions with a view to improving initial
      assessment and treatment planning. STUDY DESIGN: The study was a retrospective
      case review of seven patients. SETTING: Multidisciplinary team evaluation in a
      tertiary hospital referral center. PATIENTS: Patients with unusual lesions of the
      cerebellopontine angle and posterior fossa with initial retrocochlear symptoms
      and signs were included. INTERVENTIONS: Diagnostic and therapeutic. MAIN OUTCOME
      MEASURES: Hearing preservation and balance function. RESULTS: The rare lesions
      presented include two aneurysms of the anterior inferior cerebellar artery, one
      giant basilar artery aneurysm, and one each of the following neoplasms:
      endodermal cyst, choroid plexus papilloma, cavernous angioma, and ependymoma.
      CONCLUSIONS: A close working relationship among the otolaryngologist,
      neurotologist, neurosurgeon, and neuroradiologist is necessary to accurately
      evaluate these unusual cerebellopontine angle lesions and effect the best
      treatment outcome.

PMID- 9149836
TI  - Uncommon lesions presenting as tumors of the internal auditory canal and
      cerebellopontine angle.
AB  - OBJECTIVE: The aim of this study was to identify distinguishing characteristics
      of uncommon lesions of the cerebellopontine angle (CPA) and internal auditory
      canal (IAC) in order to attain the correct diagnosis and thus formulate an
      appropriate therapeutic protocol. STUDY DESIGN: A retrospective chart analysis
      was performed on all patients with surgically managed lesions of the IAC and CPA
      referred to neuropathology from January 1985 to April 1996. SETTING: All patients
      were treated by New York University faculty at a tertiary referral center.
      PATIENTS: Among 426 surgical cases identified, 384 patients (90.1%) with acoustic
      neuromas and 18 patients (4.2%) with meningiomas were excluded. The remaining 24
      cases, involving 17 women and seven men with a median age of 34 years, were
      analyzed. INTERVENTION: Most patients underwent audiovestibular evaluations, as
      well as magnetic resonance imaging (MRI) and computed tomographic (CT) scanning,
      and all patients underwent neurotologic surgery as part of their management
      protocol. MAIN OUTCOME MEASURES: Correlating patient presentation, preoperative
      imaging, and surgical findings often identified distinguishing characteristics of
      unusual CPA and IAC lesions. RESULTS: Unusual lesions identified at the CPA and
      IAC included: four epidermoids, four lipomas, two facial neuromas, two arachnoid
      cysts, two choroid plexus papillomas, two metastatic adenocarcinomas, one
      metastatic neuroblastoma, one ependymoma, one lymphoma, one cholesterol cyst, one
      angioleiomyoma, one venous hemangioma, one cavernous angioma, and one pontine
      glioma. CONCLUSIONS: Preoperative tumor differentiation based on the patient
      history, physical examination, audiovestibular testing, CT, and MRI help the
      surgeon to formulate an appropriate treatment protocol.

PMID- 9149837
TI  - Meningiomas intrinsic to the geniculate ganglion.
AB  - OBJECTIVE: To present the clinical, surgical and histopathological manifestations
      of meningioma intrinsic to the geniculate ganglion. STUDY DESIGN: Retrospective
      study of outcome. SETTING: Three private tertiary and one university
      (otology/neurotology) referral centers. PATIENTS: Six patients with cranial nerve
      VII paresis underwent magnetic resonance imaging and/or high-resolution computed
      tomography for subsequently histologically proven intrinsic meningioma of the
      geniculate ganglion. An additional six cases were identified in the literature.
      Most patients were female and ranged in age from 5 to 40 years. INTERVENTION:
      Total tumor removal via middle fossa and mastoid exposures followed by cable
      graft VII-VII neuroanastomosis. MAIN OUTCOME MEASURE: Meningioma can occur
      intrinsic to the geniculate ganglion and produces gradual VIIth nerve paresis as
      its first symptom. Other sites of predilection may occur extrinsically within the
      temporal bone or along intracranial venous sinuses at sites of arachnoid villi.
      RESULTS: Hearing was maintained in each patient, and postoperative House
      Brackmann grade III-V facial nerve function was achieved. CONCLUSIONS: Intrinsic
      meningiomas of the geniculate ganglion rarely occur. However, this entity should
      be included in the differential diagnosis of a slowly progressive VIIth nerve
      paresis, especially in young females. Surgical removal and cable graft VII-VII
      neuroanastomosis is the treatment of choice. Long-term follow-up should be
      maintained because of the potential for von Recklinghausen's disease.

PMID- 9149838
TI  - Vagal nerve monitoring: a comparison of techniques in a canine model.
AB  - HYPOTHESIS: An optimal technique exists for intraoperative, electrophysiologic
      vagal nerve monitoring. BACKGROUND: Analogous to facial nerve monitoring during
      lateral skull base surgery, vagal nerve monitoring may be used at surgery
      involving the jugular foramen, the posterior cranial fossa, the infratemporal
      fossa, the parapharyngeal space, and the thyroid gland to decrease the incidence
      of iatrogenic injuries. Laryngeal electromyography (EMG) is an accurate test of
      vagal nerve function: four applications have been described for use
      intraoperatively. The purpose of this study was to compare the sensitivities of
      these techniques in a canine model in order to identify the optimal method of
      intraoperative vagal nerve monitoring. METHODS: Four techniques of EMG vagal
      nerve monitoring were studied in dogs. The thyroarytenoid muscle (TA) was
      monitored directly in three techniques. Two methods used bipolar hookwire
      electrodes (L.A. Diagnostics, Los Angeles, CA) inserted in the TA percutaneously
      through the cricothyroid membrane or via direct laryngoscopy (DL). The third TA
      monitoring technique involved the use of an EMG endotracheal tube (Xomed-Treace,
      Jacksonville, FL). The fourth technique used a laryngeal surface EMG electrode
      (RLN Systems, Jefferson City, MO), laryngoscopically placed in the postcricoid
      space. After placing each monitoring device, the vagus nerve was identified
      bilaterally in the neck. The nerves were sequentially stimulated at a constant
      current of 4.1 Hz with increasing intensity (starting at 0.05 mAmps) to determine
      the minimum thresholds to stimulate vocal cord contraction. A positive response
      at the vocal cord was defined as a train of four contractions of > or = 50 mV.
      The lowest threshold for each technique in each dog was recorded. RESULTS: A
      positive response was obtained in 27 of 32 possible cases using a maximum
      boundary of 0.5 mAmps for stimulus intensity. Survival analysis was then used to
      generate Kaplan-Meier survival curves, allowing a comparison of the mean time
      needed to obtain a response. Log-rank chi statistics showed that the survival
      curves are inhomogenous (degrees of freedom [df] = 3, chi = 15.58, p < 0.001).
      The laryngeal surface electrode appears to offer the most sensitive method for
      vagal nerve monitoring. CONCLUSIONS: Four techniques of intraoperative, EMG vagal
      nerve monitoring were compared in a canine model. The results suggest that EMG
      recordings can be obtained successfully through a variety of techniques and that
      the laryngeal surface electrode appears to be the most sensitive technique in the
      canine model.

PMID- 9149839
TI  - Preoperative electroneuronography and facial nerve outcome in acoustic neuroma
      surgery.
AB  - OBJECTIVE: To determine whether preoperative electroneuronography (ENoG) predicts
      facial nerve outcome in patients undergoing acoustic neuroma surgery. STUDY
      DESIGN: Prospective, consecutive patients undergoing surgery for acoustic
      neuroma. SETTING: A private tertiary otology and neurotology practice. PATIENTS:
      One hundred consecutive patients presented for surgical removal of an acoustic
      neuroma between May 1992 and September 1993. The mean patient age was 49 years
      (range 17-77). Forty-three percent were male and 57% were female. The mean tumor
      size was 1.77 cm (range 3 mm to 5 cm). The tumors were removed by a
      translabyrinthine approach in 59% of patients, via the middle fossa in 40%, and
      retrosigmoid in 1%. The facial nerve was anatomically intact at the conclusion of
      the operation in all but one patient. INTERVENTION: Preoperative ENoG in all
      patients undergoing surgical removal of their acoustic neuromas. MAIN OUTCOME
      MEASURES: Facial nerve outcome was measured using the House-Brackmann scale
      immediately after the operation. 5-7 days after surgery, and > 1 year after
      surgical resection. RESULTS: Preoperative ENoG had no predictive value in
      determining immediate or eventual facial nerve outcome. CONCLUSIONS: ENoG has no
      value in predicting the facial nerve outcome in acoustic neuroma patients. The
      results of this study are similar to reports with smaller series in the
      literature. Preoperative ENoG has proven useful, in another study from this
      institution, in predicting the possible presence of a facial nerve neuroma. This
      test may be helpful in determining the possible etiology of an intracanalicular
      mass.

PMID- 9149840
TI  - Imaging case of the month: cochlear otosclerosis.

PMID- 9149841
TI  - Morpholino and phosphorothioate antisense oligomers compared in cell-free and in
      cell systems.
AB  - Morpholino and phosphorothioate (S-DNA) antisense oligos were compared in both
      cell-free and in-cell translation systems. In the most stringent test of
      specificity in the cell-free system, a globin-targeted S-DNA oligo was found to
      inhibit its target sequence at concentrations of 10 nM and above, but the
      sequence-specific component of this inhibition dropped below 50% at
      concentrations of 100 nM and above. A corresponding Morpholino oligo achieved
      even higher inhibition at 10 nM, but in contrast to the S-DNA, with the
      Morpholino, the sequence-specific component of this inhibition remained above 93%
      at a concentration of 3000 nM. In this same cell-free test system, several S-DNA
      oligos exhibited substantial undesired nonantisense effects at concentrations of
      300 nM and above, whereas corresponding Morpholino oligos exhibited little or no
      nonantisense activity through a concentration of 3000 nM. In scrape-loaded HeLa
      cells, both globin-targeted and HBV-targeted S-DNAs (both antisense and control
      oligos) generally failed to achieve significant translational inhibition at
      extracellular concentrations up to 3000 nM. In contrast, the Morpholino oligos
      achieved effective and specific translational inhibition at extracellular
      concentrations ranging from 30 nM to 3000 nM.

PMID- 9149842
TI  - Comparative pharmacokinetics, tissue distribution, and tumor accumulation of
      phosphorothioate, phosphorodithioate, and methylphosphonate oligonucleotides in
      nude mice.
AB  - The goals of this study were to systematically compare the pharmacokinetics and
      tissue distribution of phosphorothioate (PS), methylphosphonate (MP), and
      phosphorodithioate (PS2) oligonucleotide analogs; 15-mers of sequence d-TAC GCC
      AAC AGC TCC (5'-3') complementary to the AUG region of K-ras were radiolabeled
      with carbon-14. Oligomers were administered as a single dose in the tail vein of
      nude mice harboring a K-ras-dependent human pancreatic tumor (CFPAC1). The
      kinetics of PS, PS2, and MP oligomer availability in the bloodstream was
      followed. Concentration versus time profiles for all oligomers were biphasic,
      indicative of a two-compartment model. A rapid distribution phase with t1/2 alpha
      values of 1 minute or less and an elimination phase with average t1/2 beta values
      of 24-35 minutes were observed. Volumes of distribution (Vd) were 3.2, 4.8, and
      6.3 ml for PS2, MP, and PS, respectively, in comparison to 3.6 ml for sucrose, a
      fluid-phase marker. Relative tissue drug levels obtained at 1 and 24 hours after
      administration were kidney > liver > spleen > tumor > muscle. Total kidney and
      liver oligonucleotide accumulation was approximately 7%-15% of the initial dose,
      with tumor accumulating 2%-3%. Intact compound was recovered from all tissues,
      including tumor, as assessed by high-pressure reversed-phase HPLC coupled to
      radiometric detection. Integrity of the oligonucleotides ranged from 73% in blood
      to 43%-46% in kidney and liver. Kidney and liver appear to be the primary sites
      of metabolism. These results demonstrate widespread tissue availability of these
      compounds and suggest their development as potential antitumor agents.

PMID- 9149843
TI  - A helix 1-extended hairpin ribozyme exhibits altered cleavage behavior in vitro.
AB  - The catalytic domain of a hairpin ribozyme was incorporated at the 3'-end of a
      254-base antisense RNA directed against the RNA of human immunodeficiency virus
      type 1 (HIV-1), generating a hairpin ribozyme with a largely extended helix 1. In
      parallel, a catalytic antisense RNA based on a hammerhead ribozyme was directed
      toward the same cleavage motif in the HIV-1 target. Both ribozymes were expected
      to create identical cleavage products. Cleavage analysis in vitro confirmed that
      the hammerhead ribozyme delivered the expected cleavage products. However, the
      helix 1-extended hairpin ribozyme catalyzed additional RNA cleavage at several
      unexpected sites, which were mapped. Some of the 3' cleavage products had other
      nucleotides than G at their 5'-terminus, indicating that the helix 1-extended
      hairpin ribozyme was able to cleave bonds other than NpG+1. Inspection of the
      sequence context of the different cleavage sites suggested that unconventional
      helices 2 in combination with an asymmetric loop A consisting of up to 32
      unpaired nucleotides in the substrate strand were formed. A second variant of a
      helix 1-extended hairpin ribozyme that differed in two nucleotides gave
      consistent results.

PMID- 9149844
TI  - Characterization and evaluation of NGF antisense oligonucleotides: inhibition of
      NGF synthesis in transfected COS cells.
AB  - We present a system for the assessment of the inhibiting capacity of antisense
      oligonucleotides. The aim of this study was to identify an oligonucleotide that
      can inhibit chicken nerve growth factor (NGF) synthesis. Five antisense chicken
      NGF phosphorothioate oligonucleotides, AS1-5, were designed and were tested for
      their capacity to inhibit NGF expression in COS cells. COS cells that transiently
      expressed chicken NGF were treated with the oligonucleotides, and NGF expression
      was analyzed using a bioassay and Western blotting for NGF protein. Two
      oligonucleotides, AS 1 and AS 5, were more capable than the others of inhibiting
      expression compared with nonsense oligonucleotide, and they targeted the
      translational initiation and stop sites. The chicken NGF is expressed at a high
      level from an adenovirus major late promoter, and AS 1 was capable of inhibiting
      more than 80% of the NGF expression as determined using the bioassay and Western
      blotting. Expression of another member of the NGF gene family, neurotrophin-4,
      was not affected by treatment of the antisense oligonucleotides. A 10-fold lower
      concentration of the AS 1 oligonucleotide could be used to inhibit NGF synthesis
      if the cellular uptake was facilitated using lipofectin compared with addition of
      oligonucleotide directly to the culture medium. The amount of oligonucleotide
      taken up by the cells was similar in the lipofectin-treated cells as in the cells
      treated by a 10-fold higher concentration of medium-supplemented nucleotide. This
      system based on COS cells can facilitate evaluation of the capacity of inhibiting
      antisense oligonucleotides, particularly targeting those genes in which
      endogenous products are present in low levels and are difficult to analyze.

PMID- 9149845
TI  - Effects of S-dC28 on vascular smooth muscle cell adhesion and plasminogen
      activator production.
AB  - We sought to examine phosphorothioate oligodeoxynucleotide (PS oligo) non-G
      quartet, nonsequence specific effects on smooth muscle cell (SMC) adhesion by
      using S-dC28, a 28-mer cytidine homopolymer that lacks contiguous guanosine
      residues. Human aortic SMC were incubated with vehicle or various doses of S
      dC28, and the number of SMC adhered to noncoated plates was determined using a
      Coulter Counter. S-dC28 significantly inhibited SMC adhesion. SMC adhesion
      dramatically improved with S-dC28 in fibronectin-coated plates. When laminin
      coated plates were used, the inhibition of SMC adhesion by S-dC28 was completely
      reversed. Replacement of serum-free medium with 5% fetal bovine serum medium for
      SMC cultured on non-coated plates also greatly attenuated inhibition of adhesion
      by S-dC28. Human SMC TPA, UPA, and PAI-1 antigen levels were determined by
      ELISAs. PDGF significantly induced SMC TPA antigen production measured by an
      ELISA. Coincubation of PDGF with S-dC28 significantly attenuated SMC TPA antigen
      levels. SMC UPA antigen levels after coincubation with PDGF and S-dC28 were
      significantly greater than the values observed in SMC incubated in medium
      containing PDGF alone. SMC PAI-1 antigen levels were not altered by the addition
      of S-dC28. We conclude that S-dC28 inhibits human SMC adhesion and that this
      inhibition can be diminished by fibronectin or laminin coating of culture plates
      or by the presence of serum in the culture medium. Furthermore, S-dC28 attenuates
      SMC TPA production, thereby inhibiting SMC migration, whereas S-dC28 augments SMC
      UPA production, thus diminishing SMC cellular adhesion.

PMID- 9149846
TI  - Antisense oligonucleotides to p53 tumor suppressor suppress the induction of
      apoptosis by epidermal growth factor in NCI-H 596 human lung cancer cells.
AB  - Apoptosis has become a basic tool in developing cancer research and establishing
      new cancer strategies. However, the molecular mechanism of apoptosis is not well
      understood. Recently, the authors found that epidermal growth factor (EGF)
      induces apoptosis in various cancer cells and that there is a novel signal
      pathway mediated through p53 in signal transduction of EGF. The effect of
      antisense gene therapy to p53 tumor suppressor on EGF-dependent apoptosis was
      investigated in cultured NCI-H 596 human non-small cell lung cancer cells with a
      wild-type p53 gene. Results showed that EGF plus p53 sense oligonucleotides
      induced EGF-dependent and p53-dependent apoptosis in NCI-H 596 cells within 8
      hours. On the other hand, antisense gene therapy using antisense oligonucleotides
      to p53 tumor suppressor suppressed the induction of EGF-dependent and p53
      dependent apoptosis. Mutated p53 antisense-containing mutated CG dinucleotides
      had the same effect as that of p53 antisense on suppression of apoptosis in NCI-H
      596 cells. We found that a new nucleic acid drug, another mutated p53 antisense
      containing mutation at three bases immediately 5' and 3' from the CG
      dinucleotides, potentiated the induction of apoptosis and failed to suppress the
      induction of EGF-dependent apoptosis. These results suggest that gene therapy
      using antisense oligonucleotides to the p53 tumor suppressor is effective on EGF
      dependent apoptosis of NCI-H 596 human non-small cell lung cancer.

PMID- 9149847
TI  - Identification of an oligodeoxynucleotide sequence motif that specifically
      inhibits phosphorylation by protein tyrosine kinases.
AB  - Protein tyrosine kinases (PTKs) have central roles in cellular signal
      transduction. We have identified a sequence motif (CGT[C]GA) in phosphorothioate
      modified oligodeoxynucleotides (ODNs) that specifically inhibits the enzymatic
      activity of recombinant or immunoprecipitated PTK in vitro. Hexamer ODNs
      containing this motif block both substrate and autophosphorylation of at least
      four different PTKs but have no apparent effect on the enzymatic activity of a
      serine/threonine protein kinase. These data suggest possible new applications for
      ODNs and have implications for the design and interpretation of experiments using
      antisense or triplex ODNs.

PMID- 9149848
TI  - Triplex-forming oligonucleotides with unexpected affinity for a nontargeted GA
      repeat sequence.
AB  - We examined the affinity and the specificity of triplex formation for different
      purine ODNs directed against two portions of a purine sequence derived from the
      mouse fli-1 gene. As expected, the ODNs antiparallel to the purine strand of
      their target can form triplex DNA. One parallel ODN showed binding to its target
      sequence. We explain this unusual binding by an interaction of the ODN with a GA
      repetition present in the sequence. We further examined the interaction of this
      ODN with a target composed of 14 GA repetitions. Unexpectedly, one ODN shows
      higher affinity for a partially complementary GA target relative to its
      completely complementary target. For another ODN, the binding to the GA target is
      weaker and might involve skipping of bases in a way that resembles alternate
      strand triplex formation.

PMID- 9149849
TI  - In vivo labeling of over-expressed recombinant proteins in E. coli.

PMID- 9149850
TI  - Expression of the highly toxic centromere binding protein CENP-B in E. coli using
      the pET system in the absence of the inducer IPTG.

PMID- 9149851
TI  - Increased efficiency in screening large numbers of cDNA fragments generated by
      differential display.

PMID- 9149852
TI  - XcmI-containing vector for direct cloning of PCR products.

PMID- 9149853
TI  - High-efficiency human B-cell cloning using hygromycin B-resistant feeder cells.

PMID- 9149854
TI  - Rapid mapping and subcloning of genomic clones in bacteriophage lambda by PCR.

PMID- 9149855
TI  - PCR-based assay to determine nuclear matrix association.

PMID- 9149856
TI  - Spatial visualization of apoptosis using a whole-mount in situ DNA end-labeling
      technique.

PMID- 9149857
TI  - Direct in situ end-labeling for detection of apoptotic cells in tissue sections.

PMID- 9149858
TI  - Optimized factor V gene mutation detection using buffy-coat direct PCR.

PMID- 9149859
TI  - Spectrophotometric determination of oxidative metabolism.

PMID- 9149860
TI  - Protein staining with Ponceau S during acid-urea-triton-polyacrylamide gel
      electrophoresis.

PMID- 9149861
TI  - Isolation of nuclear proteins from human brains.

PMID- 9149862
TI  - Use of a single sequencing termination reaction to distinguish between cytosine
      and 5-methylcytosine in bisulfite-modified DNA.

PMID- 9149863
TI  - Hyaluronidase generates a single-cell suspension from cultured mouse lung
      epithelial cells.

PMID- 9149864
TI  - pPE1000: a versatile vector for the expression of epitope-tagged foreign proteins
      in transgenic plants.

PMID- 9149865
TI  - Two products for siliconizing glass plates used in gel electrophoresis.

PMID- 9149866
TI  - Rapid method for preparing adenovirus DNA.

PMID- 9149867
TI  - Microplate digestion of minipreps from a single microcentrifuge tube.

PMID- 9149868
TI  - Isolation of genomic DNA from claw clippings for genetic analysis in chickens.

PMID- 9149869
TI  - Increased yield of plasmid DNA during removal of CsCl by ethanol precipitation.

PMID- 9149870
TI  - Determining the potentiative state of a chromatin domain.

PMID- 9149871
TI  - PCR-amplified cDNA probes for verification of differentially expressed genes.
AB  - Differential display has proven to be a powerful technique for the detection and
      isolation of differentially expressed genes. By generating reproducible cDNA
      expression patterns, it is possible to compare gene expression by two or more
      cell types, developmental stages or tissues and to isolate as yet unknown
      differentially expressed genes. A sensitive method is necessary to verify the
      differential expression of the isolated cDNAs. Here we describe the use of
      adaptor-ligated. PCR-amplified total cDNA of the two cell types compared as a
      probe for Southern hybridizations with the isolated cDNAs.

PMID- 9149872
TI  - Agglutination-inhibition assay for the detection of recombinant proteins tagged
      with peptide epitopes.
AB  - We have demonstrated that the expression of recombinant proteins labeled with an
      immunoreactive epitope can be rapidly assessed and quantitated using a modified
      haemagglutination inhibition assay in enzyme-linked immunosorbent assay (ELISA)
      trays. The agglutination of erythrocytes from a droplet of whole blood provided a
      simple visual assay. The additional reagents required for the assay were a
      recombinant anti-human erythrocyte Fab fragment fused to a peptide epitope and a
      bivalent antibody with specificity to the same epitope. In this report, we found
      that a convenient and sensitive epitope was the octapeptide FLAG in conjunction
      with the M2 anti-FLAG antibody, which had affinity to FLAG incorporated either at
      the C-terminus or N-terminus of the recombinant protein. The agglutination
      inhibition (AI) assay was configured to detect as little as 1 mg/L of soluble
      recombinant protein in a 30-min assay. Since the AI assay was substantially more
      rapid and convenient than dot-blot or Western blot analyses, our laboratory now
      uses this method routinely for the assay of FLAG-labeled recombinant products
      following protein expression and subsequent small- and large-scale purification
      procedures.

PMID- 9149873
TI  - Transient selection during vaccinia virus recombination with insertion vectors
      without selectable markers.
AB  - Isolation of recombinant viruses after DNA transfection remains the most time
      consuming and labor-intensive feature in the production of vaccinia virus (VV)
      recombinants. This procedure has been aided by the design and incorporation of
      both positive and negative selectable markers into the insertion vectors. Use of
      these selectable markers is not always feasible or desirable. In the absence of
      selectable markers, individual plaque characterization is required. A method of
      transient selection during transfection and recombination is described that does
      not require that any selectable marker be present in the insertion vector
      sequence. This method relies on the co-transfection of a guanine phosphoribosyl
      transferase (gpt) selectable marker on an unlinked plasmid into VV-infected cells
      pretreated for gpt selection. Following recombination, the output virus can be
      plated on cells without any further selection and screened for recombinant virus.
      While the total recombinant virus population is slightly reduced, the total
      progeny virus is reduced even further, resulting in more than sevenfold
      enhancement in the frequency of recombinant virus, which allows for more
      efficient identification.

PMID- 9149874
TI  - Cloning DNA fragments between two adjacent/overlapping restriction sites using a
      "positive stuffer".
AB  - Here we describe a solution to a common problem encountered in recombinant DNA
      cloning when directional cloning of a DNA fragment into a predetermined plasmid
      requires the use of restriction enzymes with adjacent or overlapping recognition
      sites. In preparing the double-digested plasmid, only one enzyme will often cut,
      whereas the second will not because of the lack of a sufficiently long stretch of
      double-stranded DNA at its recognition site. The problem can be solved by
      construction of a "user-friendly" intermediary plasmid in which the desired
      restriction sites are separated by a positively selectable stuffer with
      resistance to neomycin. This approach is particularly useful in cases where the
      choices of restriction sites are severely limited, for example, when it is
      necessary to clone an additional piece of DNA into a complex vector already
      containing multiple gene cassettes.

PMID- 9149875
TI  - Making hybrids of two-hybrid systems.
AB  - Two-hybrid systems are powerful tools to find new partners for a protein of
      interest. However, exchange of material between two-hybrid users has been
      handicapped by the various versions of two-hybrid systems available and by the
      widely accepted idea that they are not compatible. In the present paper we show
      that, contrary to the dogma, the most often used two-hybrid systems may be
      combined by either transformation or mating assays. The protocol to be followed
      in each case is provided. This will greatly increase the prospects of the growing
      network of interacting proteins, by reconciling the "two-hybrid systems" and the
      "interaction trap".

PMID- 9149876
TI  - Adaptation of a beta-1,3-glucanase assay to microplate format.
AB  - A method is described for performance of a beta-1,3-glucanase assay in
      microplates. The adaptation to microassay format has been made possible through
      the availability of heat-stable microplates. Assay samples containing beta-1,3
      glucanase (cell extracts) and the substrate are mixed in 96-well, autoclavable
      microplates. Incubation of the enzyme-substrate mixture results in the release of
      reducing sugars by the action of beta-1,3-glucanase. The levels of these sugars
      are colorimetrically quantified through the addition of "copper reagent" and
      neocuproine, incubation at 100 degrees C for 10 min and the resulting reduction
      of Cu+2 to Cu+. A standard curve of glucose concentrations within the same plate
      allows for assessment of internal variance. Twenty samples can be assayed in one
      microplate in 1 h, compared to the 96 test tubes and 4 h needed for traditional
      assay methods. The net savings in reagents used with the microplate format is
      substantial. The measurement of optical density is performed rapidly for all of
      the samples, eliminating the problem of oxidization of Cu+ to Cu+2 during
      quantification. This method represents a significant savings in time, chemicals
      and cost.

PMID- 9149877
TI  - Association of enzyme inhibition with methods of museum skin preparation.
AB  - Enzyme inhibition is commonly encountered when using molecular biological
      techniques on museum-prepared animal skin samples, and this problem is
      exacerbated by a lack of information on how particular skins have been prepared
      for preservation. This report: (i) demonstrates that while some methods of museum
      preparation inhibit both proteinase K digestion and the PCR, others do not; (ii)
      describes a change in buffer conditions that reduces proteinase K enzyme
      inhibition during tissue digestion: and (iii) uses electron-dispersive X-ray
      microanalysis (EDXA) to show that the preparation methods for museum-preserved
      skin are often more complex than the treatment description provided with samples
      and also suggests that some of these descriptions are incorrect.

PMID- 9149878
TI  - Detection of mycoplasma infection of mammalian cells.
AB  - Mycoplasma infection was detected in cultures of COS cells with a novel, simple
      assay that detects the conversion of arginine to citrulline by the enzyme,
      arginine deiminase, specific to all species of mycoplasma. Transfection of COS
      cells was inhibited in mycoplasma-infected cells, a phenomenon that was readily
      reversed by treatment with a mycoplasma removal agent. Cultures of cells used for
      transfection should be regularly monitored for evidence of mycoplasma by assay of
      arginine deiminase activity or by other methods.

PMID- 9149879
TI  - An iterative and regenerative method for DNA sequencing.
AB  - This paper presents, to our knowledge, the first iterative DNA sequencing method
      that regenerates the product of interest during each iterative cycle, allowing it
      to overcome the critical obstacles that impede alternative iterative approaches
      to DNA sequencing: loss of product and the accumulation of background signal due
      to incomplete reactions. It can sequence numerous double-stranded (ds) DNA
      segments in parallel without gel resolution of DNA fragments and can sequence DNA
      that is almost entirely double-stranded, preventing the secondary structures that
      impede sequencing by hybridization. This method uses ligation of an adaptor
      containing the recognition domain for a class-IIS restriction endonuclease and
      digestion with a class-IIS restriction endonuclease that recognizes the adaptor's
      recognition domain. This generates a set of DNA templates that are each composed
      of a short overhang positioned at a fixed interval with respect to one end of the
      original dsDNA fragment. Adaptor ligation also appends a unique sequence during
      each iterative cycle, so that the polymerase chain reaction can be used to
      regenerate the desired template-precursor before class-IIS restriction
      endonuclease digestion. Following class-IIS restriction endonuclease digestion,
      sequencing of a nucleotide in each overhang occurs by template-directed ligation
      during adaptor ligation or through a separate template-directed polymerization
      step with labeled ddNTPs. DNA sequencing occurs in strides determined by the
      number of nucleotides separating the recognition and cleavage domains for the
      class-IIS restriction endonuclease encoded in the ligated adaptor, maximizing the
      span of DNA sequenced for a given number of iterative cycles. This method allows
      the concurrent sequencing of numerous dsDNA segments in a microplate format, and
      in the future it can be adapted to biochip format.

PMID- 9149880
TI  - Alternative system for detection and mapping of activation domains.
AB  - The ZEBRA protein is a transcriptional activator that induces expression of viral
      lytic genes in cells harboring latent Epstein-Barr virus (EBV). In this report it
      is shown that a derivative of ZEBRA that cannot activate transcription (Zd) can
      be used to detect and characterize activation domains. Three expression vectors
      that allow the fusion of putative activation regions in any reading frame were
      constructed using Zd. These vectors were used to demonstrate the activity of
      different classes of activation domains using a chloramphenicol acetyltransferase
      (cat) reporter gene construct containing seven ZEBRA response elements (Z7). The
      Zd/Z7 system effectively detected proline-rich, glutamine-rich and acidic
      activation domains in a variety of cell lines and cell types. Using a bioassay
      unique to the EBV Zd/Z7 system, fusion constructs can also be tested for the
      ability to activate gene expression directly from a chromatin structure, the EBV
      genome. These studies indicate that the Zd/Z7 system is an alternative to GAL4
      and can be a useful tool for identifying heterologous activation domains.

PMID- 9149881
TI  - Optimization of cellular ELISA for assay of surface antigens on human
      synoviocytes.
AB  - The cellular enzyme-linked immunosorbent assay (CELISA) permits assay of cell
      surface antigens on intact fixed cells. Using a monolayer of cells as the solid
      phase, the CELISA offers an inexpensive alternative to flow cytometry. In
      addition, this protocol has the decided advantages of miniaturization (small
      numbers of cells) and ease of replication (the 96-well cluster plate format). In
      efforts to optimize CELISA for detecting surface antigens on human fibroblastlike
      synoviocytes, the authors found that cell number, serum proteins, choice of
      culture plate, pipetting technique and fixatives may all impact the results of
      the CELISA.

PMID- 9149882
TI  - Microplate assay for measurement of histamine release from mast cells.
AB  - A microplate-format assay for measurement of histamine release by activated rat
      peritoneal mast cells, with accompanying microplate-format spectrofluorometric
      assay of histamine, is demonstrated. Reproducibility and linearity of the
      histamine assay are comparable to the historical large format assay. Transfer of
      samples in the 96-well format, from histamine release through spectrofluorometric
      assay, greatly expedites handling and provides for better independence of each
      replicate. A sample experiment is included to show a typical size experiment
      easily done in this format.

PMID- 9149883
TI  - Simultaneous detection of multiple point mutations using fluorescence-coupled
      competitive primer extension.
AB  - We report the development of a method for the simultaneous genotyping of several
      distinct nucleotide positions by means of fluorescence-coupled competitive primer
      extension. We demonstrate the application of this method for the simultaneous
      detection of three point mutations in the human mitochondrial genome, at
      nucleotide positions 3460, 11778 and 14484, which account for about 90% of cases
      with Leber's hereditary optic neuropathy. mtDNA fragments encompassing these
      nucleotide positions are initially amplified in a multiplex PCR assay. Genotyping
      is then carried out by a simultaneous primer extension assay using wild-type
      specific (FAM-labeled) and mutant-specific (JOE-labeled) oligonucleotides. Primer
      extension products are separated on a 6% polyacrylamide/8 M urea gel on a
      fluorescence DNA sequencer. Patients' genotypes can be derived from the peak
      color of the different-sized extension products. As little as 10% mutant DNA can
      be detected in heteroplasmic mixtures of wild-type and mutant mtDNA, a degree
      that is sufficient for routine clinical practice.

PMID- 9149884
TI  - Collagen-coated Ba(2+)-alginate microcarriers for the culture of anchorage
      dependent mammalian cells.
AB  - Several types of microcarriers suitable for large-scale cultivation of mammalian
      cells are commercially available. However, many of these carriers have
      disadvantages, e.g., the need for enzymatic digestion for cell harvesting, size
      limitations and insufficient biocompatibility. These limitations have been
      overcome by the development of collagen-coated Ba(2+)-alginate microcarriers.
      Ba(2+)-alginate microspheres, made with the air-jet droplet generator technique,
      were collagen-coated by incubation in a 0.5% collagen solution, with subsequent
      gelling of the collagen layer around the alginate microspheres. Human chang liver
      (CCL-13) and mouse fibroblast (L929) cell lines were cultivated in stationary,
      unstirred cultures as model systems. After a lag phase of nearly 24 h, the cells
      grew rapidly on these microcarriers and reached confluence after 3 days. The
      microcarrier cultures were stable for an additional 4-9 days and longer. Cells
      were harvested either by trypsinization or by dissolution of the alginate matrix
      using 5 mM EDTA. The main advantages of this new microcarrier system are that the
      preparation procedure is easy and can be accomplished on demand with standard
      laboratory equipment.

PMID- 9149885
TI  - Agarose-based system for separation of short tandem repeat loci.
AB  - Short tandem repeats (STRs) are traditionally analyzed on large polyacrylamide
      electrophoresis gels. We demonstrate in this study that a small (10-cm-long, 1-mm
      thick) agarose gel is sufficient for analysis of multiplexed samples for several
      commonly used STR loci. A system was developed using a high-resolution agarose,
      MetaPhor. Within an hour of electrophoresis, sufficient resolution was obtained
      to allow discrimination of triple-multiplexed STR loci. We show that this agarose
      is capable of resolving di- as well as tetranucleotide ladders. Using PCR
      conditions similar to those routinely used with sensitive detection systems, we
      found that direct staining of gels with SYBR Green I stain was comparable with
      silver staining, autoradiography or fluorescently tagged primers for sample
      detection and was considerably easier. This procedure significantly simplifies
      STR analysis and is much faster than many standard protocols.

PMID- 9149886
TI  - The PerFect lipid optimizer kit for maximizing lipid-mediated transfection of
      eukaryotic cells.
AB  - The transfection efficiencies of a panel of eight uniquely different lipid
      reagents has been evaluated with two other commercially available lipids for use
      in transfecting a diversity of eukaryotic cell lines. The PerFect lipids are
      available individually or together in an optimization panel format that can be
      tested in any given cell line, enabling one to evaluate the optimal lipid for
      transfecting each individual cell line. Our results demonstrate that no single
      lipid is optimal for plasmid transfection over a broad range of cell types, thus
      emphasizing the need for multiple unique lipid reagents and a simple format for
      testing their transfection efficiency on a given cell type.

PMID- 9149887
TI  - Risk of breast cancer associated with atypical hyperplasia of lobular and ductal
      types.
AB  - Epidemiological studies using the histological classification of Page for benign
      breast disease consistently demonstrate a positive association between atypical
      hyperplasia and the subsequent development of breast cancer. However, atypical
      hyperplasia is of either lobular or ductal types, and breast cancer risk in
      relation to type of atypical hyperplasia has not been studied extensively. Thus,
      we investigated prospectively the risk of breast cancer associated with
      histological subtypes of benign proliferative breast disease, including the types
      of atypical hyperplasia, among participants in the Nurses' Health Study who had
      biopsy-confirmed benign breast disease. Women who subsequently developed breast
      cancer were matched by year of birth and year of biopsy to participants who were
      free from breast cancer. Benign biopsy slides were classified according to the
      criteria of Page. Odds ratios (ORs) of breast cancer and 95% confidence intervals
      (CIs), adjusted for the matching variables and other breast cancer risk factors,
      were computed using unconditional logistic regression with benign
      nonproliferative breast disease as the referent group. Atypical ductal
      hyperplasia (OR = 2.4; 95% CI, 1.3-4.5) or atypical lobular hyperplasia (OR =
      5.3; 95% CI, 2.7-10.4) in a prior biopsy were associated with increased breast
      cancer risk. Atypical lobular hyperplasia was more strongly associated with the
      risk of premenopausal breast cancer (OR = 9.6; 95% CI, 3.3-27.8) than with the
      risk of postmenopausal breast cancer (OR = 3.7; 95% CI, 1.3-10.2). The
      association of atypical ductal hyperplasia and breast cancer risk varied little
      by menopausal status. The magnitude of breast cancer risk seems to vary according
      to the type of atypical hyperplasia present at biopsy.

PMID- 9149888
TI  - Human erythrocyte glucose transporter (Glut1) is immunohistochemically detected
      as a late event during malignant progression in Barrett's metaplasia.
AB  - We have previously demonstrated that the human erythrocyte glucose transporter
      (Glut1) is expressed in adenocarcinoma arising in Barrett's metaplasia (BM). We
      have also shown that Glut1 is expressed as a late event during colorectal
      carcinogenesis. The aim of this work was to determine the chronology of Glut1
      expression during the neoplastic progression in Barrett's metaplasia. Formalin
      fixed, paraffin-embedded tissue sections of 251 biopsies from 97 patients with BM
      were immunostained with the anti-Glut1 antibody MYM, after microwave-aided
      antigen retrieval, using the standard avidin-biotin complex immunoperoxidase
      technique. Dysplasia was graded as negative (ND), low grade (LGD)/indefinite or
      high grade (HGD). None of the 181 biopsies with ND (0%) or 51 biopsies with LGD
      (0%) showed Glut1 immunoreactivity. More importantly, although 0 of 6 biopsies
      with HGD (0%) expressed Glut1, 9 of 13 biopsies with adenocarcinoma (69%) were
      Glut1 positive (P = 0.0108, Fisher's exact test). Our results indicate that Glut1
      is expressed as a late event during the neoplastic progression in BM. Prospective
      studies are needed to determine the clinical utility of Glut1 immunoreactivity as
      a marker of carcinoma in patients with BM.

PMID- 9149890
TI  - Smoking, gender, and survival association with allele loss for the LOH11B lung
      cancer region on chromosome 11.
AB  - We have reported frequent allele loss for the marker HRAS on chromosome 11p in
      human lung cancer and defined the smallest common region of deletion (designated
      LOH11B) to approximately 500 kb. Here, we investigated the association of allele
      loss for LOH11B with epidemiological, pathological, and clinical parameters.
      Analysis of allele loss was performed using Southern blotting on a cohort of 200
      patients with lung cancer, and data were interpreted with the use of a
      phosphorimager. Results were statistically compared with retrospectively
      collected variables. LOH11B allele loss was significantly associated with
      cigarette consumption (P = 0.009), gender (P = 0.02), and survival (P = 0.04).
      None of the nonsmokers had allele loss as compared with 28% of the patients with
      low and 43% with high cigarette consumption. Allele loss was more frequent in men
      (43%) than in women (11%). The median survival of patients without allele loss
      was 42 months compared with 25 months for patients with allele loss. These
      results suggest that the LOH11B region contains a gene responsible for a more
      malignant phenotype independent of the metastatic potential of lung cancer. They
      also suggest that alterations in this gene are associated with cigarette
      consumption and are more frequent in men than in women.

PMID- 9149889
TI  - Hierarchical modeling of gene-environment interactions: estimating NAT2 genotype
      specific dietary effects on adenomatous polyps.
AB  - Data sparseness currently limits gene-environment interaction estimation. To
      improve effect estimates of gene-environment interactions, we give an overview of
      one approach, hierarchical modeling, and propose a two-stage hierarchical model.
      The first stage is a logistic model for the joint effects of the genetic and
      environmental factors. The second stage regresses the joint effects on genotype
      specific enzymatic activity of the environmentally derived substrate. The model
      is illustrated using a case-control study of adenomas of the large bowel, for
      which NAT2 genotype and dietary data were collected. The first-stage interactions
      of dietary components and genotype were regressed on initial conversion rates of
      dietary heterocyclic amines to aryl nitrenium ions. We fit the hierarchical model
      by penalized likelihood. Compared to effect estimates from maximum-likelihood
      logistic regression, hierarchical results are more reasonable and precise. These
      results lend further support to previous observations that hierarchical
      regression is preferable to ordinary logistic regression when multiple factors
      and their interactions are being studied. We propose that hierarchical modeling
      can act as a bridge between molecular epidemiology studies and laboratory data,
      combining both efficiently.

PMID- 9149891
TI  - Cigarette smoking and chromosome 9 alterations in bladder cancer.
AB  - Epidemiological studies suggest that bladder cancer may be caused by carcinogens
      in tobacco and certain occupational exposures. Molecular studies have shown that
      chromosome 9 alterations and TP53 mutations are the most frequent events in
      bladder cancer. To date, the relationships between epidemiological risk factors
      and genetic alterations have not been fully explored in bladder cancer. The
      purpose of this study was to explore the association between smoking and
      chromosome 9 aberrations in bladder cancer cases. Seventy-three patients with
      bladder cancer at Memorial Sloan-Kettering Cancer Center were evaluated for
      smoking history, occupational history, and chromosome 9 alterations. The
      epidemiological data were abstracted from medical charts. Patients' tumor tissues
      were analyzed using RFLP and microsatellite polymorphism assays for detection of
      chromosome 9 alterations. Elevated odds ratios (ORs) were found for chromosome 9
      alterations in smokers compared to those in nonsmokers (OR = 4.2; 95% confidence
      interval, 1.02-17.0) after controlling for age, sex, race, occupational history,
      and stage of disease. The ORs were 3.6 for those smoking < or = 20 cigarettes per
      day and 5.8 for those smoking > 20 cigarettes per day. No association was found
      between occupational history and chromosome 9 alterations. This study supplies
      evidence suggestive of the link between smoking and chromosome 9 alterations in
      the etiology of bladder cancer and indicates that potential tumor suppressor
      genes on chromosome 9 may be involved in smoking-related bladder carcinogenesis.

PMID- 9149892
TI  - Temporal variation in chlorinated hydrocarbons in healthy women.
AB  - Chlorinated hydrocarbons may increase breast cancer risk. Most epidemiological
      studies addressing this possibility have used one biological sample to measure a
      subject's cumulative exposure to these compounds. Little is known about short
      term temporal variation in organochlorines, particularly in individuals with low
      levels. Thus, the reliability of using one sample to assess blood levels of
      chlorinated hydrocarbons in an epidemiological study is unknown. To better
      understand the temporal changes in blood measures among women with
      nonoccupational exposures to these compounds, we collected two 5-ml blood
      samples, an average of 2 months apart, from each of 31 nonfasting healthy women,
      ages 45-81 years. Samples were assayed for 1,1-dichloro-2,2-bis(p
      chlorophenyl)ethylene (DDE), polychlorinated biphenyls (PCBs), and trans
      nonachlor in blinded, matched pairs. Results were adjusted for estimated total
      plasma lipids. The correlations between the two blood samples were high for DDE
      and PCBs (lipid-adjusted, r = 0.96 and r = 0.89, respectively). For trans
      nonachlor, the correlation was relatively poor (lipid-adjusted r = 0.57);
      however, with the removal of one outlier, the correlation improved substantially
      (lipid-adjusted, r = 0.90). The mean difference between the two blood samples in
      unadjusted [-0.36 ng/ml, 95% confidence interval (CI), -0.97, 0.24 ng/ml, P =
      0.23] and lipid-adjusted (-0.035 microgram/g lipid; 95% CI, -0.124, 0.055; P =
      0.44) DDE levels was small. Similarly, there was little change in the mean
      difference for unadjusted (-0.14 ng/ml; 95% CI, -0.53, 0.25 ng/ml; P = 0.47) and
      lipid-adjusted (0.006 microgram/g lipid; 95% CI, -0.050, 0.062; P = 0.82) PCB
      levels. The mean differences in trans-nonachlor levels between the two blood
      draws were also small: unadjusted (-0.03 ng/ml; 95% CI, -0.07, 0.02 ng/ml; P =
      0.20) and lipid-adjusted (-0.003 microgram/g lipid; 95% CI, -0.010, 0.004; P =
      0.33). These data suggest that temporal changes in organochlorine levels within a
      1 to 3-month period are minimal for noncancer patients and that a single measure
      for estimating exposure is highly reliable for DDE and PCB. For trans-nonachlor,
      however, where the correlation between blood draws was lower, three samples would
      be needed for estimating exposure; if an outlier is removed from our data,
      however, then we can conclude that only a single measure is sufficient. These
      data, therefore, offer no clear conclusion for the use of a single measurement
      for trans-nonachlor.

PMID- 9149893
TI  - Reduced aliquot size for a plasma organochlorine assay for use in epidemiological
      studies.
AB  - Because archived blood specimens are an important but limited resource for
      conducting epidemiological studies using biomarkers, it is important to develop
      analytical techniques that minimize the amount of sample needed. We modified an
      established 1.0-ml blood plasma organochlorine assay to use smaller volumes. We
      assessed its utility by comparing the accuracy and precision of measurements
      obtained with different-sized aliquots of spiked plasma from three pools of known
      concentration of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and
      polychlorinated biphenyls (PCBs; low, medium, and high). There was a modest
      sacrifice in accuracy using 0.5 as opposed to 1.0 ml. However, the within-batch
      coefficients of variation, a measure of laboratory error, were consistently low
      when 0.5-ml aliquots were used. For both DDE and PCB concentrations, this error
      was less than 5% for the medium and high pools [5-20 parts per billion (ng/ml)]
      and less than 9% for the low pool (< 1 part per billion). After determining that
      aliquots of 0.5 ml were sufficient, we performed a blinded quality control
      analysis of stored plasma. In this study, the within-subject variation was low
      for DDE and PCBs and substantially lower than the between-subject variation,
      suggesting that the assay would rank subjects with reasonable precision. Our
      results suggest that use of 0.5-ml as opposed to 1.0-ml aliquots should not
      compromise the power of a nested case-control study to detect differences between
      subjects and would thus save plasma for future research. For populations with
      very low levels of organochlorines, however, the larger volumes should still be
      used.

PMID- 9149894
TI  - Urinary phytoestrogen levels in young women from a multiethnic population.
AB  - Phytoestrogens include several classes of chemical compounds (i.e., isoflavones,
      coumestans, and lignans) which are structurally similar to endogenous estrogens.
      In biological systems, they have both estrogenic and antiestrogenic effects and
      may reduce the risk of developing certain types of hormonally related diseases.
      However, little information is available on population differences in exposure to
      phytoestrogens. To examine racial/ethnic differences in urinary phytoestrogen
      levels, 50 young women (ages 20-40 years) were randomly selected from
      participants in a previous epidemiological study in which 24-h urine specimens
      and a dietary assessment were obtained. Subjects were members of the Kaiser
      Permanente Medical Care Program of northern California. Selection was stratified
      on race/ethnicity. Urinary levels of seven phytoestrogens were measured using
      high-performance liquid chromatography-mass spectrometry. Substantial variation
      in phytoestrogen levels was observed and racial/ethnic differences are described.
      The highest levels of coumestrol and the lignans were observed in white women and
      the lowest levels in Latina and African American women. Genistein levels,
      however, were highest in Latina women; other isoflavone levels did not differ
      significantly by race/ethnicity.

PMID- 9149896
TI  - Application of a behavioral approach to measuring dietary change: the fat- and
      fiber-related diet behavior questionnaire.
AB  - This study reports the validity, reliability, and responsiveness of a 33-item fat
      and fiber-related behavior questionnaire (FFB) and describes how this instrument
      provides insight into the process of adopting healthy diets. Data are from the
      Eating Patterns Study, a randomized clinical trial of a physician-delivered, self
      help intervention to reduce fat and increase fiber intake. Intervention (n = 850)
      and control participants (n = 945) completed both a food frequency questionnaire
      and the FFB at baseline and at 3 and 12 months postintervention. Validity, as
      assessed by correlation of the FFB with the food frequency questionnaire at
      baseline, was 0.53 for fat (fat scale with percentage energy from fat) and 0.50
      for fiber (fiber scale with fiber g/1000 kcal; both P < 0.001). Reliability, as
      assessed by the intraclass correlation in controls across all three time points,
      was 0.77 for the fat scale and 0.74 for the fiber scale (both P < 0.001). The
      largest changes in fat-related behavior were in avoiding fat as a flavoring and
      in using specially manufactured low-fat foods, and the largest changes in fiber
      related behavior were in substituting high-fiber versions of common foods.
      Overall, the FFB was a reasonably valid and reliable measure of dietary intake,
      which provided insight into the behavioral effects of the dietary intervention.

PMID- 9149895
TI  - Use of a food frequency questionnaire to screen for dietary eligibility in a
      randomized cancer prevention phase III trial.
AB  - Cancer prevention clinical trials use food frequency questionnaires (FFQs) to
      assist in eligibility screening. FFQ reliability and validity studies are
      available, but these studies do not evaluate FFQs as screening tools. The Wheat
      Bran Fiber Trial of the University of Arizona used a FFQ as an eligibility screen
      with the goal of screening out subjects whose true daily calcium intake was less
      than 500 mg per day (for safety) and whose true dietary fiber intake was greater
      than 30 g per day (for safety and trial efficiency). Subjects ineligible by FFQ
      were interviewed for final dietary eligibility determinations. A study was
      undertaken within the Wheat Bran Fiber Trial to evaluate the sensitivity,
      specificity, positive predictive value, and negative predictive value (NPV) of
      the FFQ used in this context. Four-day food records were collected on 183
      potential participants before entry into the study. Using the 4-day averages as
      the "true" value, sensitivity, specificity, positive predictive value, and NPV
      were calculated for men and women separately under two screening conditions:
      using the target calcium and dietary fiber values and using "revised" values
      identified in interim analysis within the study. NPV was acceptable in all
      analyses. Sensitivity for low calcium intake was inadequate under the original
      criteria (0.33 for men and 0.09 for women) but acceptable under the revised
      criteria (0.80 for men and 0.81 for women). With the revised criteria,
      specificity declined, resulting in heavy screening burdens deemed worthwhile for
      the safety considerations. Dietary fiber eligibility screening worked well at
      target values. These differences were not predicted by reliability/validity
      studies.

PMID- 9149897
TI  - Serum responses to the combination of Epstein-Barr virus antigens from both
      latent and acute phases in nasopharyngeal carcinoma: complementary test of EBNA-1
      with EA-D.
AB  - Elevated serum IgA to antigens of EBV is associated with nasopharyngeal carcinoma
      (NPC). We have tested 620 NPC sera by ELISA for the presence of antibodies to EBV
      encoded DNA binding protein, EBV-specific DNA polymerase, early antigen-diffused
      (EA-D), EBV nuclear antigen 1 (EBNA-1), EBV-specific thymidine kinase, and BamHI
      Z fragment EBV replication antigen. Sensitivity of these proteins was in the
      range of 51.5-79.5% for IgA and 69.4-82.8% for IgG. The complementary use of EBNA
      1 with EA-D, however, could increase the sensitivity significantly to 98.1%.
      Western blot analysis further showed that the combination of EBNA-1 and EA-D is
      most useful for the detection of NPC. This is the first report of using double
      biomarkers including EBV gene products from both latent and active infections.
      The results of this study suggest that EBV in NPC may not be latent alone and
      that the method may be valuable for the early detection, early treatment, and
      better survival rate of patients with NPC. Because the application of recombinant
      EBV protein in ELISA is cost-effective and feasible for mass screening, the
      method may be of worth for further clinical investigation.

PMID- 9149898
TI  - Etiology of Barrett's metaplasia and esophageal adenocarcinoma.
AB  - The incidence of esophageal adenocarcinoma in the United States is rising at an
      epidemic rate. Although the cause for this rapid rise is unclear, it is well
      established that nearly all cases of esophageal adenocarcinoma arise from a
      premalignant lesion of the esophagus, known as Barrett's esophagus. Although
      Barrett's esophagus is recognized as a precursor lesion, the etiology,
      prevalence, and malignant risk of this lesion remain unclear. The relatively
      short, two-decade time frame for the rise in esophageal adenocarcinoma incidence
      and the increase across populations is a strong argument for environmental
      factors as etiological agents, perhaps interacting with genetically determined
      characteristics that define personal susceptibility. Because of the strong link
      between Barrett's esophagus and esophageal adenocarcinoma and the link between
      Barrett's esophagus and gastroesophageal reflux disease, risk factors for
      gastroesophageal reflux disease have been the prime suspects offered as possible
      explanations for the rise in esophageal adenocarcinoma. A plethora of hypotheses
      have been advanced, implicating tobacco and alcohol consumption, changes in
      obesity and diet, and the changing pattern in use of medications that affect the
      upper gastrointestinal tract. The following text will review what is currently
      known about the epidemiology of Barrett's metaplasia, its risk for malignant
      transformation, and the proposed theories of etiogenesis.

PMID- 9149899
TI  - Third international workshop on collaborative interdisciplinary studies of p53
      and other predisposing genes in Li-Fraumeni syndrome.

PMID- 9149900
TI  - Distinct roles of the receptor tyrosine kinases c-ErbB and c-Kit in regulating
      the balance between erythroid cell proliferation and differentiation.
AB  - In the bone marrow, multipotent and committed hematopoietic progenitors have to
      closely regulate their balance between sustained proliferation without
      differentiation (self renewal) and entering a terminal differentiation pathway. A
      useful model to analyze this regulation at the molecular level is committed avian
      erythroid progenitors. These are induced to undergo long-term self renewal by the
      ligand-activated receptor tyrosine kinase (RTK) c-ErbB, in cooperation with
      steroid hormone receptors. This self-renewal induction by c-ErbB even occurs in
      the presence of differentiation factors (erythropoietin and insulin). Under the
      same conditions, the RTK c-Kit is unable to sustain erythroid progenitor self
      renewal, stimulating cell proliferation without arresting terminal
      differentiation. Two mechanisms are involved in these differential activities of
      c-Kit and c-ErbB. The first one, differential regulation of receptor expression,
      proved to be of minor importance, because c-Kit was unable to induce self
      renewal, even if exogenously expressed from a retrovirus at high levels. Rather
      our results support the second mechanism, i.e., that receptor-specific signal
      transduction is responsible for the differential biological activity of c-Kit and
      c-ErbB: (a) specific tyrosine kinase inhibitors (tryphostins) were found which
      selectively inhibited the biological function of either c-Kit or c-ErbB in
      erythroblasts but did not affect ligand-induced autophosphorylation of either
      RTK; and (b) c-ErbB selectively induced SHC phosphorylation and STAT5 activation.
      The Ras pathway was similarly activated by c-Kit and c-ErbB. The c-ErbB-specific
      tyrphostin AG30 specifically blocked STAT5 activation, implicating this signal
      transducer in c-ErbB-induced self renewal.

PMID- 9149901
TI  - C-Jun and JunD suppress maturation of chondrocytes.
AB  - To analyze the function of AP-1 in cartilage formation, two types of primary
      chondrocytes, LS and US cells, were prepared from caudal (lower) and cephalic
      (upper) regions of chicken sterna, respectively. All the known components of
      chicken AP-1 (c-Fos, Fra-2, c-Jun, and JunD) were detected in both cell types,
      but the expression level of c-Jun was much higher in LS cells, which are rich in
      less mature chondrocytes than US cells. In the sterna, the expression level of c
      Jun was also lower in the maturating or hypertropic chondrocytes than in
      proliferating chondrocytes. When US cells were treated with parathyroid hormone
      (PTH), which prevented maturation as judged from the maturation-associated
      markers such as alkaline phosphatase and type X collagen, the expression levels
      of c-Jun and JunD were constitutively elevated. To analyze the possible
      relationship between differentiation status and expression levels of Jun family
      proteins, they were exogenously introduced into the entire population of US cells
      within 2 days by using high titer, replication-competent retroviral vectors.
      Maturation-associated markers in US cells were specifically lowered by exogenous
      expression of c-Jun or JunD to similar levels to those of LS cells or US cells
      treated with PTH. When US cells were infected with the virus encoding a dominant
      negative mutant of AP-1 (supJunD-1), maturation markers were moderately increased
      10 days after infection. The potent induction of alkaline phosphatase activity in
      US cells by all-trans retinoic acid was annulled by exogenous expression of
      either c-Jun or JunD. These results suggest that Jun family proteins negatively
      regulate the maturation process of chondrocytes.

PMID- 9149902
TI  - Differential expression of MEK1 and MEK2 during mouse development.
AB  - Map/Erk kinase 1 (MEK1) and MEK2 activate the Erk/ MAP kinases and have been
      implicated in cell growth and differentiation. To investigate the role of MEKs
      during mouse development, we have examined their expression and activity in
      various murine tissues during embryonic development and in the adult mouse. MEK2
      RNA message is expressed at high levels in all embryonic tissues examined,
      including all neural tissues, and liver. This can be observed by in situ
      hybridization of tissue sections of 14.5-day-old mouse embryos, as well as by
      Northern blot analyses. MEK1, on the other hand, is expressed at very low levels
      in most embryonic murine tissue but can be detected in developing skeletal
      muscle. It is expressed at higher levels in adult tissue, particularly in brain,
      where it is expressed at high levels. Western blot analyses of MEK1 and MEK2 in
      14.5-day-old embryonic and adult mouse tissue confirm the RNA analysis. Levels of
      MEK1 kinase activity are particularly high in adult brain tissues as well. These
      findings suggest that MEK2 may be the primary Erk/MAP kinase activator during
      development and that MEK1 may play a role in the proliferative or mitogenic
      response in adult mouse tissues. This study also raises the possibility that MEK1
      and MEK2 might not have redundant functions in cells but may possess unique
      specificity in their interactions with upstream activators or downstream targets.

PMID- 9149903
TI  - Short-chain fatty acid-initiated cell cycle arrest and apoptosis of colonic
      epithelial cells is linked to mitochondrial function.
AB  - Butyrate, a short-chain fatty acid produced during microbial fermentation of
      fiber, induces growth arrest, differentiation, and apoptosis of colonic
      epithelial cells in vitro, and our prior work has shown that this induction is
      tightly linked to mitochondrial activity. Here we demonstrate that 12 h following
      induction, SW620 human colonic carcinoma cells accumulate simultaneously in G0-G1
      and G2-M of the cell cycle. Four h later, during this G0-G1 to G2-M arrest, cells
      begin to undergo apoptosis. Using a series of unrelated agents that modulate
      mitochondrial functions, we demonstrate that mitochondrial electron transport and
      membrane potential are critical in initiation of this butyrate-mediated growth
      arrest and apoptosis. Colonic tumorigenesis is characterized by abnormalities in
      proliferation, apoptosis, and mitochondrial activities. Thus, butyrate may reduce
      risk for colon cancer by inducing a pathway that enhances mitochondrial function,
      ultimately resulting in initiation of growth arrest and apoptosis of colonic
      epithelial cells.

PMID- 9149904
TI  - Transfection of rhabdomyosarcoma cells with connexin43 induces myogenic
      differentiation.
AB  - Normal cell physiological processes rely heavily on cues from the extracellular
      environment to coordinate the proper functioning of cellular activities. The
      intercellular communication that takes place through gap junctions in neighboring
      cells has been implicated in growth control and embryonic differentiation.
      Indeed, many tumorigenic cells induced to overexpress gap junction proteins
      exhibit increased differentiation and decreased cell proliferation. Although
      absent in mature skeletal muscle, studies have demonstrated that gap junctions
      are present during the early stages of myogenesis, indicating their possible role
      in muscle development. In our present study, we have attempted to induce a more
      differentiated phenotype in communication-deficient rhabdomyosarcoma cells. These
      tumorigenic human cells were transfected with cDNA encoding the gap junction
      protein connexin43 (Cx43) such that clones of varying expression were isolated.
      Intercellular communication as measured with dye passage assays was directly
      proportional to the level of Cx43 expressed, and in those cells expressing Cx43
      at high levels, a marked increase in cell membrane fusion and myosin expression
      was observed. Furthermore, clones expressing Cx43 at high levels exhibited a
      significant reduction in growth rate when grown under nonadhesive conditions, an
      indication that their tumorigenicity had been reduced. This apparent increase in
      myogenic differentiation lends further evidence to the possible role of gap
      junctional coupling during developmental processes.

PMID- 9149905
TI  - Immortalization of primary epithelial cells by E1A 12S requires late, second exon
      encoded functions in addition to complex formation with pRB and p300.
AB  - Immortalization of primary cells is an early and important event in multistep
      tumorigenesis and is itself a multistep process. Adenovirus E1A 12S encodes an
      oncoprotein that can rescue cells from senescence and overcome apoptosis, leading
      to their immortalization. Five regions of 12S, located in both exons, are
      required for immortalization. Two regions in the first exon are necessary to
      activate the cell cycle, increase the number of population doublings, and
      overcome the M1 stage of mortality. However, extension of life span requires
      overcoming crisis or M2, which can be accomplished by the expression of the
      second exon. Several cellular proteins associate with the peptide encoded by the
      first exon of 12S including pRB, p107, p130, and p300. The importance of pRB-E1A
      and p300-E1A complexes in transformation is well established; however, their
      roles in 12S-mediated immortalization remain undefined. Results obtained from the
      present study using a panel of second exon immortalization-defective mutants
      demonstrate that formation of pRB-E1A and p300-E1A complexes is insufficient for
      immortalization of primary cells. We further demonstrate that the expression
      levels of another tumor suppressor protein, p53, also do not correlate with the
      inability of the mutants to immortalize. Thus, mutations in the second exon of
      12S do not affect the early steps in the immortalization pathway. The second exon
      mutants are defective in performing a late function in immortalization, involving
      the reactivation of the cell cycle, indicating that it is a crucial event in
      immortalization.

PMID- 9149906
TI  - Expression patterns of the E2F family of transcription factors during murine
      epithelial development.
AB  - The E2F family of transcription factors includes five E2F and three DP forms. E2F
      is involved in the regulation of cell proliferation, but little is known about
      E2F function during vertebrate development. We have explored the regulation of
      E2F expression during mouse organogenesis by in situ hybridization. We find
      selective up-regulation of E2F-2, E2F-4, and E2F-5 transcripts in epidermis and
      intestinal epithelium at important developmental stages. E2F-4 transcript levels
      are high in early, undifferentiated single-cell-layer ectoderm, and later in 13.5
      14.5-day-postcoitus (dpc) embryo epithelium, which contains several layers of
      proliferating cells. E2F-2 is up-regulated following the onset of E2F-4
      expression and is first apparent in undifferentiated epithelium at 13.5-14.5 days
      of gestation. In contrast, E2F-5 transcripts are detected later in gestation,
      once the epidermis shows evidence of stratification. Stratification of the
      epidermis into basal, proliferating cells and suprabasal, terminally
      differentiating cells at 15.5-19.5 days of gestation coincides with expression of
      E2F-2 and E2F-4 in basal cells and of E2F-5 in suprabasal cells. Similarly, in
      intestinal epithelium, E2F-4 up-regulation in pseudostratified epithelium at 13.5
      days of gestation precedes appearance of E2F-2 transcripts, in 14.5-dpc embryos,
      in the proliferating, intervillus epithelium. In 16.5-19.5-dpc embryos, no E2F-2
      transcripts were detected at the tip of the developing villi, which contain
      terminally differentiating cells. In contrast, E2F-5 transcripts were limited to
      the upper half of the villi and were absent in the intervillus epithelium. This
      suggests that E2F-2 and E2F-4 may participate in maintaining epithelial cells in
      a proliferative, undifferentiated phenotype, whereas E2F-5 may be important to
      maintain the differentiated state. Thus, selective regulation of E2F forms occurs
      during murine epithelial development, irrespective of the ectodermal or
      endodermal origin of such epithelia.

PMID- 9149907
TI  - Phosphatidylinositol 3-kinase inhibitor wortmannin blocks mitogenic activation of
      the transferrin receptor gene promoter in late G1.
AB  - Expression of the transferrin receptor is necessary for cells to progress through
      S-phase. The transferrin receptor gene promoter is activated as a delayed event
      following growth factor stimulation of quiescent fibroblasts. Serum stimulation
      in the presence of vanadate leads to superactivation of the transferrin receptor
      promoter, suggesting a role for tyrosine phosphorylation. Wortmannin, a potent
      inhibitor of phosphatidylinositol 3-kinase, a tyrosine kinase-regulated enzyme,
      blocks mitogen-dependent activation of the transferrin receptor promoter.
      Furthermore, wortmannin was able to block activation of this promoter when added
      several hours after serum stimulation of quiescent cells. This suggests that
      phosphatidylinositol 3-kinase may be required in mid to late G1 and that it is
      directly involved in a pathway leading to activation of the transferrin receptor
      promoter. This is further supported by the finding that the transferrin receptor
      promoter is much less responsive to mitogenic stimulation in cells that have been
      stably transfected with a dominant negative form of the phosphatidylinositol 3
      kinase regulatory subunit. Activation of S6 kinase, an event known to be
      downstream of phosphatidylinositol 3-kinase activation, appears not to be
      involved in activation of the transferrin receptor promoter since no effect was
      observed by treatment of cells with rapamycin.

PMID- 9149908
TI  - Time correlation of commitment to calcium-induced apoptosis and terminal
      differentiation in human ectocervical keratinocytes in suspension cultures.
AB  - The terminal differentiation of epithelial keratinocytes has been proposed to be
      a specialized form of programmed cell death (apoptosis). We examined the time
      correlation of apoptosis and terminal differentiation by human ectocervical
      keratinocytes in a suspension culture that induces either of these events in
      epithelial cells. We found that a loss of cell anchorage did not result in the
      immediate onset of apoptotic DNA degradation but sensitized the cells to that
      triggered by calcium. This susceptibility appeared in parallel with the
      irreversible loss of growth potential and the accumulation of involucrin,
      suggesting that the ectocervical keratinocytes in suspension become competent to
      calcium-inducible apoptosis as they committed to terminal differentiation.
      Cycloheximide, which inhibited the calcium induction of DNA fragmentation, was
      also inhibitory to terminal differentiation. These correlations support the
      notion that terminal differentiation of keratinocytes couples with apoptosis.
      Apoptosis seemed to be independent of p53 because it was down-regulated in
      suspension cultures of ectocervical keratinocytes.

PMID- 9149909
TI  - Triggering of HLA-DR antigens differentially modulates tumor necrosis factor
      alpha release by B cells at distinct stage of maturation.
AB  - Triggering of HLA class II antigens by the anti-HLA-DR monoclonal antibody (mAb)
      L243 significantly (P < 0.05) and differentially enhanced the release of tumor
      necrosis factor alpha (TNF-alpha) by the non-Hodgkin's lymphoma cells Ri-I, Ci-I,
      and Sc-I, which are at a distinct stage of B-cell differentiation, and by the
      more mature Burkitt lymphoma cell Raji; in contrast, it did not induce TNF-alpha
      release by the pre-B leukemia cells Nalm-6 and BV173. TNF-alpha release peaked at
      24 h and decreased thereafter, and it was dose dependent and preceded by an
      increase of TNF-alpha mRNA detectable after 3 h of stimulation with mAb L243.
      Secreted TNF-alpha mediated the enhancement of nuclear factor kappa B (NF-kappa
      B) and activator protein-1 (AP-1) binding activity; in fact, the triggering of
      HLA-DR antigens in the presence of antihuman TNF-alpha-neutralizing antibodies
      did not upregulate NF-kappa B and AP-1. In contrast, released TNF-alpha was not
      responsible for the homotypic aggregation of Ri-I, Ci-I, Sc-I, and Raji cells
      induced by mAb L243, and it did not affect the proliferation of B cells
      investigated. Altogether, our data demonstrate that: (a) the ability of B cells
      to release TNF-alpha after triggering of HLA-DR antigens depends on their stage
      of differentiation; (b) levels of released TNF-alpha seem to correlate with the
      stage of B-cell maturation but do not correlate with the amounts of cell surface
      HLA-DR antigens; (c) secreted TNF-alpha regulates the levels of expression of NF
      kappa B and AP-1 by an autocrine loop; and (d) intracellular signals mediating
      TNF-alpha release by B cells are distinct from those regulating homotypic
      aggregation and proliferation.

PMID- 9149910
TI  - Response of a primary human fibroblast cell line to H2O2: senescence-like growth
      arrest or apoptosis?
AB  - Hydrogen peroxide has been shown to induce either apoptosis or features of
      senescence in different cultured cell lines. We now show that both processes can
      be induced in the same culture of primary human diploid fibroblasts and that the
      outcome of apoptosis or the senescence-like phenotype is determined by the H2O2
      concentrations. At 50 and 100 microM, H2O2 predominantly induced the senescence
      like state, characterized by a reduced rate of proliferation, an increased number
      of cells in G0-G1, typically enlarged and flattened morphology, and increased
      CIP1 and fibronectin expression. At 300 and 400 microM, H2O2 mainly triggered
      apoptosis. At the intermediate 200 microM H2O2, features of both senescence and
      apoptosis were observed in the same culture. Thus, the higher the H2O2
      concentration, the higher the proportion of cells undergoing apoptosis,
      suggesting a key role of the level of damage in the choice of a cell population
      to enter apoptosis and/or the senescence-like state. Before the induction of one
      or the other process, cells entered a transient "shock state" characterized by a
      typical morphological change, cell cycle arrest in G0-G1, and the induction of
      CIP1 and BCL-2.

PMID- 9149911
TI  - Differential expression of nucleoskeleton- and cytoskeleton-associated proteins
      in Burkitt lymphoma-derived and Epstein-Barr virus-immortalized lymphoblastoid
      cell lines.
AB  - Mouse monoclonal antibodies raised against nuclear bodies isolated from an EBV
      immortalized lymphoblastoid cell line (LCL) known to contain several viral and
      cellular proteins (Jiang et al., Exp. Cell Res., 197: 314-318, 1991; Szekely et
      al., J. Gen. Virol., 76: 2423-2432, 1995; Szekely et al., J. Virol., 70: 2562
      2568, 1996). Seventy six clones gave detectable immunofluorescence staining on
      LCLs. Five independent monoclonal antibodies detected a group of apparently
      novel, high M(r) (> 200,000) proteins that shared common features of subcellular
      distribution. In LCLs, these proteins were preferentially associated with
      vimentin filaments in the cytoplasm and with distinct nuclear foci. The
      appearance of the latter differed from the premyelocytic leukemia-associated
      protein, EBV nuclear antigen #5, and retinoblastoma-protein-positive bodies that
      were used for immunization. They seemed to be connected to the cytoplasmic
      filaments through thin fibrillar nuclear structures. In mitotic cells, these
      complex structures rearranged into a perichromosomal basket that was associated
      with vimentin filaments. The target proteins, operationally designated as
      proteins associated with nuclear dots and cytoplasmic filaments (pNDCFs), were
      not present in resting human B cells or were expressed at a low level. The level
      increased considerably after EBV infection or mitogenic stimulation by
      interleukin 4 and anti-CD40 antibodies. In Burkitt lymphoma (BL) type I lines
      phenotypically representative of the in vivo tumors, the pNDCFs were either
      absent or exclusively localized to the nucleus, usually to well-defined nuclear
      foci. EBV-positive type I BLs often shift to a more LCL-like (type III) phenotype
      during prolonged in vitro propagation. Type I cells express only EBV nuclear
      antigen 1 and the surface markers CD10 and CD77, whereas type III express all
      nine growth-associated EBV-encoded proteins and a gamut of B-cell activation
      markers. Most of the type III BL cell lines contained increased amounts of pNDCFs
      bound to cytoplasmic filaments, as seen in the LCLs. We propose that the
      expression of vimentin-associated pNDCFs should be included in the definition of
      type III BL phenotype.

PMID- 9149912
TI  - Ontogeny and localization of an oncostatin M-like protein in the rat testis: its
      possible role at the start of spermatogenesis.
AB  - Oncostatin M (OSM), a member of the interleukin 6 family of cytokines, was found
      to be highly expressed in the late fetal and early neonatal rat testis, as well
      as in the maturing and adult testis. Two different forms of OSM were observed,
      one of M(r) 22,000 and the other of M(r) 36,000. In the prepubertal rat testis
      [19 days post coitum, 8 days post partum (dpp), and 15 dpp], the form with the
      higher molecular weight prevailed, whereas in the maturing testis (30 dpp, 45
      dpp, and 12 weeks post partum), a shift toward the lower molecular weight form
      was observed, as well as a decrease in its relative amount. By
      immunohistochemistry on testicular sections, OSM-specific immunostaining was
      observed in the interstitial tissue at every age studied. In contrast, OSM
      immunoreaction was localized in the Sertoli cells exclusively around the start of
      spermatogenesis, being strongest at 3 dpp. In vitro studies revealed that
      neonatal Sertoli cells produce OSM. The possible role of OSM at the start of
      spermatogenesis was investigated by using a coculture of Sertoli cells and
      gonocytes isolated from newborn rats. OSM significantly increased the survival of
      both Sertoli cells and gonocytes in a dose-dependent manner. The proliferative
      activity of the Sertoli cells was not affected by OSM, whereas that of gonocytes
      was increased by almost 60% after 6 days of culture. Comparison of the effect of
      OSM on these cocultures with other members of the interleukin 6 family of
      cytokines demonstrated that this factor is more potent than leukemia inhibitory
      factor or ciliary neurotrophic factor. On the basis of these findings, it can be
      concluded that OSM is present in the rat testis, and it is likely to play an
      important role at the start of spermatogenesis.

PMID- 9149913
TI  - The Q-Prep system: effects on the apparent expression of leucocyte cell surface
      antigens.
AB  - To facilitate the analysis of immunolabelled peripheral blood or bone marrow
      leucocytes by flow cytometry, a number of reagents are available commercially
      that lyse erythrocytes and fix leucocytes. This study has investigated the effect
      on antibody-labelled whole blood of the Q-Prep procedure, in which erythrocytes
      are lysed with formic acid, and leucocytes are fixed with formaldehyde. Whole
      blood samples were labelled with the nuclear dye LDS-751 and with antibodies to
      HLA-DR or belonging to CD2, CD3, CD4, CD7, CD8, CD10, CD13, CD14, CD19, CD20,
      CD29, CD33, CD45, CD45RA, CD56, and CD62L (TQ-1) that were directly conjugated to
      either phycoerythrin (PE) and/or fluorescein isothiocyanate (FITC). Leucocytes
      were analysed by flow cytometry either in unfixed, unlysed whole blood (15) or
      after preparation using the Q-Prep system. The binding of eight antibodies, CD19
      FITC, CD2-PE, CD3-PE, CD4-PE, CD19-PE, CD29-PE, CD45RA-PE, and CD56-PE, to the
      surface of lymphocytes was reduced, resulting in significant changes (P < 0.05)
      in the percentages of cells that stained positively and/or their mean molecules
      of equivalent fluorochrome (MEF). Further analysis revealed that this was due to
      the formic acid used during the erythrocyte lysis stage.

PMID- 9149914
TI  - Toward a new reference method for the leukocyte five-part differential.
AB  - A flow cytometric method performing a five-part leukocyte differential based on
      three-color staining with anti-CD45-fluorescein isothiocyanate (FITC), anti-CD-14
      phycoerythrin (PE)/Cy5, and a cocktail of PE-labeled anti-CD2, anti-CD16, and
      anti-HLA-DR antibodies was evaluated. Results obtained by using three different
      sample preparation procedures and two different flow cytometers were compared
      with those of a 1,000-cell manual differential for evaluation of accuracy. We
      observed excellent correlations with the manual differential for all leukocyte
      subclasses and even higher correlations between the different flow cytometric
      methods. Flow cytometric basophil results were identical to the manual counts,
      regardless of which sample preparation technique or flow cytometer was used.
      Therefore, we propose our flow cytometric method as the first acceptable
      automated reference method for basophil counting. The flow cytometric results for
      the other leukocyte subclasses were apparently influenced by the sample
      preparation, which could not be explained by cell loss during washing steps.
      Moreover, a small influence of the flow cytometer was also observed. Assessing
      the influence of sample storage, we found only minimal changes within 24 h. In
      establishing reference values, high precision of flow cytometric results
      facilitated detection of a significantly higher monocyte count for males
      (relative count: 7.08 +/- 1.73% vs. 6.44 +/- 1.33%, P < 0.05; absolute count:
      0.536 +/- 0.181 x 10(9)/liter vs. 0.456 +/- 139 x 10(9)/liter, P < 0.01). Our
      data indicate that monoclonal antibody-based flow cytometry is a highly suitable
      reference method for the five-part differential: It also shows, however, that
      studies will have to put more emphasis on methodological issues to define a
      method that shows a high interlaboratory reproducibility.

PMID- 9149915
TI  - Quality control study of the Italian Group of Cytometry on flow cytometry DNA
      content measurements: II. Factors affecting inter- and intralaboratory
      variability.
AB  - A multicentric national quality control study has been organized under the
      auspices of the Italian Group of Cytometry to find a possible influence of some
      procedural steps in DNA flow cytometry measurements on DNA index (DI) values and
      to identify the main parameters affecting the interlaboratory variability. To 40
      participating laboratories we provided suspensions containing unknown mixture of
      different cell types: an homogeneous thymocyte population used to check
      instrument linearity; one mixture composed of two cell types characterized by DI
      = 1.00 and 1.10; and another composed of three different cell types with relative
      DIs of 1.00, 1.26, and 1.62, respectively. Possible effects due to staining
      protocols were studied, allowing the participants to stain cellular DNA according
      to the procedure routinely adopted in each laboratory, in addition to a
      standardized procedure with a fixed PI solution. As far as the influence of
      instrument linearity on DI values is concerned, we did not find any correlation
      with the DI variability observed, even if the use of a standardized staining
      protocol could lead to a sensible gain in interlaboratory DI reproducibility.
      Twenty-five of 40 (65%) laboratories were able to discriminate the near-diploid
      subpopulation, and a coefficient of variation of less than 4% was the minimum
      condition necessary to recognize the DI = 1.1 population. In samples containing
      two aneuploid subpopulations, 25 of 35 (71.4%) laboratories showed a high
      reproducibility with the standard staining protocol and 22 of 38 (57.9%) with the
      free staining protocol. However, a sensible improvement in interlaboratory
      reproducibility emerged with respect to the previous trial.

PMID- 9149917
TI  - Comparison study results.

PMID- 9149916
TI  - Sequential immunophenotypic analysis of mast cells in a case of systemic mast
      cell disease evolving to a mast cell leukemia.
AB  - The immunophenotypic characteristics of both bone marrow (BM) and peripheral
      blood (PB) mast cells (MC), from a patient suffering from an aggressive systemic
      mast cell disease (SMCD), were sequentially analyzed by flow cytometry using
      direct immunofluorescence. Analysis was carried out at diagnosis, during clinical
      response induced by interferon alfa-2h/prednisone therapy, and later at relapse.
      Our results show that together with the CD117 and IgE characteristic markers, at
      diagnosis BM MC showed strong expression of CD11c, CD13, CD29, CD33, CD44, CD45,
      CD63, and CD71, and they were also positive for CD2, CD22, CD25, and CD54
      although at a lower level. PB MC displayed similar immunophenotypic
      characteristics although they had a lower expression of CD11c, CD25, CD33, CD63,
      CD69, and CD71 with a higher reactivity for CD117. Unlike BM MC, PB MC were
      weakly positive for CD41a and CD61. Sequential studies showed decreased numbers
      of both BM and PB MC during clinical response associated with a higher expression
      of the CD29 and CD54 adhesion molecules. In turn, clinical relapse was related to
      increased numbers of PB and BM MC together with lower CD2, CD11c, CD45, and and
      CD54 expression and a higher reactivity for the CD117 and CD25 antigens. CD2 had
      become negative at the last follow-up study. In addition, an increased proportion
      of S-phase MC was observed at relapse. These findings suggest that the assessment
      of the quantitative expression of cell-adhesion molecules and growth-factor
      receptors together with cell cycle studies of mast cells could be of value for
      monitoring therapy and predicting clinical outcome in aggressive SMCD.

PMID- 9149918
TI  - Visual attention in infant monkeys: effects of dietary fatty acids and age.
AB  - Effects of dietary essential fatty acids on visual attention were explored
      longitudinally in infant rhesus monkeys with a visual paired-comparison paradigm.
      Sets of primate faces and of patterns were presented at Weeks 2, 5, 9, and 13 to
      9 infants deficient in omega-3 fatty acids and 8 fed a standard nursery diet.
      Familiarization to 1 member of each pair preceded simultaneous presentation of
      both stimuli. Infants fed the deficient diet showed longer individual looks in
      both immediate and 24-hr tests. Duration of looks decreased with age to familiar
      but not to novel stimuli. The proportion of time looking at the novel stimulus (%
      novel) increased with age but was not affected by diet. Look duration and % novel
      were differentially affected and may reflect different underlying processes.

PMID- 9149919
TI  - By land or by sea: the role of perceptual similarity in infants' categorization
      of animals.
AB  - In 3 experiments, the authors used an object-examining task to investigate the
      role of perceptual similarity in infants' categorization. In Experiment 1,
      infants were familiarized with a set of either perceptually similar or
      perceptually variable exemplars from 1 category and tested with novel exemplars
      from both categories. Ten-month-olds did not respond to the category in either
      condition, and 13-month-olds responded categorically in both conditions but
      somewhat differently in the 2 conditions. Experiment 2 showed that when 10-month
      olds were familiarized with similar exemplars but not with variable exemplars,
      they responded to the categorical distinction when given tests with typical
      exemplars. Experiment 3 established that 10-month-olds could differentiate among
      the exemplars. These results suggest that the perceptual similarity of the
      exemplars influences infants' recognition of categorical distinctions.

PMID- 9149920
TI  - Interpreting infant looking: the event set x event set design.
AB  - Theory, data, and mathematical models presented suggest that perceptual
      processing may be crucial in young infant cognition. Prior results indicating
      early or innate physical knowledge are reinterpreted. Assumptions that young
      infants use higher level cognitive processes to infer, reason, believe, and so on
      are challenged in favor of perceptual processes and the effects of novelty and
      familiarity. The 2-test habituation design that compares looking at the
      "possible" with looking at the "impossible" and the problems of that design are
      considered. The authors' approach, based on regression analysis of Event Set X
      Event Set factorial designs, eliminates those problems, refines gauging the
      contribution of various variables, quantifies these contributions with standard
      parameter estimation, unconfounds the crucial variables, and tests which
      variables are responsible for looking time differences. Data are presented that
      support the perceptual processing perspective. Application of the new design to 2
      seminal studies of infant cognition are suggested.

PMID- 9149921
TI  - Numerical abstraction in infants: another look.
AB  - This article examines an important finding from the literature on infant
      numerical competence. The finding, reported by P. Starkey, E. S. Spelke, and R.
      Gelman (1990), was that infants looked longer toward a visual display that was
      equal in number to an auditory set. In Experiment 1, when the procedures
      described by P. Starkey et al. were followed and duration was held constant
      across auditory sequences that varied in number, infants looked longer toward the
      display that was not numerically equivalent to the auditory set. In Experiment 2,
      when the rate and duration of the auditory sequences were varied randomly within
      infants, no significant preference for either the equivalent or nonequivalent
      visual display was shown. These results raise questions about P. Starkey et al.'s
      claims that infants can represent the numerosity of sets in different modalities
      and then perform one-one correspondence computations over them.

PMID- 9149922
TI  - Effects of bilingualism and biliteracy on children's emerging concepts of print.
AB  - Three groups of 4- and 5-year-old children were examined for their concepts of
      how print refers to language. All of the children could identify printed letters
      and their sounds but not read alone. The groups studied were monolingual speakers
      of English, bilingual speakers of French and English, and bilingual speakers of
      Chinese (Mandarin) and English. Bilingual children were equally proficient in
      both languages and were familiar with print and storybooks in both languages. The
      tasks assessed children's understanding of the general correspondence between
      print and language in which the printed form represents a word and the specific
      correspondence between a constituent of print and one of language that determines
      representation in a given writing system. The general correspondence relation
      applies to all writing systems, but the specific correspondence relation changes
      for different kinds of writing systems. Bilingual children understood better than
      monolingual children the general symbolic representation of print. The older
      Chinese-English bilingual children also showed advanced understanding of the
      specific correspondence relations in English print.

PMID- 9149923
TI  - The effect of talker variability on word recognition in preschool children.
AB  - In a series of experiments, the authors investigated the effects of talker
      variability on children's word recognition. In Experiment 1, when stimuli were
      presented in the clear, 3- and 5-year-olds were less accurate at identifying
      words spoken by multiple talkers than those spoken by a single talker when the
      multiple-talker list was presented first. In Experiment 2, when words were
      presented in noise, 3-, 4-, and 5-year-olds again performed worse in the multiple
      talker condition than in the single-talker condition, this time regardless of
      order; processing multiple talkers became easier with age. Experiment 3 showed
      that both children and adults were slower to repeat words from multiple-talker
      than those from single-talker lists. More important, children (but not adults)
      matched acoustic properties of the stimuli (specifically, duration). These
      results provide important new information about the development of talker
      normalization in speech perception and spoken word recognition.

PMID- 9149924
TI  - What's communication got to do with it? Gesture in children blind from birth.
AB  - It is widely accepted that gesture can serve a communicative function. The
      purpose of this study was to explore gesture use in congenitally blind
      individuals who have never seen gesture and have no experience with its
      communicative function. Four children blind from birth were tested in 3 discourse
      situations (narrative, reasoning, and spatial directions) and compared with
      groups of sighted and blindfolded sighted children. Blind children produced
      gestures, although not in all of the contexts in which sighted children gestured,
      and the gestures they produced resembled those of sighted children in both form
      and content. Results suggest that gesture may serve a function for the speaker
      that is independent of its impact on the listener.

PMID- 9149925
TI  - Changing relations between phonological processing abilities and word-level
      reading as children develop from beginning to skilled readers: a 5-year
      longitudinal study.
AB  - Relations between phonological processing abilities and word-level reading skills
      were examined in a longitudinal correlational study of 216 children. Phonological
      processing abilities, word-level reading skills, and vocabulary were assessed
      annually from kindergarten through 4th grade, as the children developed from
      beginning to skilled readers. Individual differences in phonological awareness
      were related to subsequent individual differences in word-level reading for every
      time period examined. Individual differences in serial naming and vocabulary were
      related to subsequent individual differences in word-level reading initially, but
      these relations faded with development. Individual differences in letter-name
      knowledge were related to subsequent individual differences in phonological
      awareness and serial naming, but there were no relations between individual
      differences in word-level reading and any subsequent phonological processing
      ability.

PMID- 9149926
TI  - Mother-child problem solving: continuity through the early childhood years.
AB  - Maternal ratings of child temperament and observed maternal behaviors in the home
      were collected when children were 18 months old. Both variables were examined as
      predictors of mothers' problem-solving behaviors with their toddlers at 30 months
      and the children's independent problem solving at 5 years. Maternal instructional
      behavior in the home at 18 months and maternal ratings of temperament at 18
      months predicted maternal behaviors when the children were 30 months old and
      child performance in a cognitive problem-solving task. Maternal cognitive
      assistance during the 18- and 30-month tasks also predicted child cognitive task
      performance in the laboratory at 5 years of age. These same maternal behaviors
      were related to the child's performance on the Wechsler Preschool and Primary
      Scale of Intelligence (D. Wechsler, 1967) at age 5, and lack of maternal
      assistance was related to teacher ratings of learning problems at age 5.

PMID- 9149927
TI  - Attachment, parenting, and peer interactions of toddler children.
AB  - The relation of parenting variables and attachment classification to peer
      relations was studied for 156 families with toddler children. Children were
      observed at 18 months of age in the home with their parents and from 18 to 24
      months of age in peer playgroups. Playgroup teachers rated the children's ability
      to get along with their peers. Also when children were 18 months, they were
      assessed with their mothers in the Strange Situation, and an attachment
      classification was made. There were significant differences in peer reactions to
      children of different attachment classifications. Insecure-resistant children
      received fewer positive reactions to their positive behaviors, and both resistant
      and avoidant children received more negative reactions to their positive
      behaviors. Hierarchical regressions were computed to examine the contribution of
      observed parent-child interactions and the attachment classification to peer
      interactions.

PMID- 9149928
TI  - Mothers' and fathers' singing to infants.
AB  - Mothers and fathers sang a song of their choice, once to their infant and once as
      if to their infant (simulated). The pitch of songs was higher and the tempo
      slower for infant-directed than for simulated versions. Listeners varying in
      child-care experience, musical background, and cultural origin reliably
      identified which of the two versions was infant-directed (Experiment 1).
      Identification accuracy was enhanced by musical training, knowledge of the
      singers' language and culture, and by greater pitch and tempo differences between
      versions. Other adult listeners who rated the singer's emotional engagement
      assigned significantly higher ratings to infant-directed than to simulated
      versions (Experiment 2). Differences in pitch and tempo between both versions
      predicted emotional engagement ratings. Finally, rating differences between
      infant-directed and simulated versions were highly correlated with identification
      accuracy.

PMID- 9149929
TI  - "You can try or you can just give up": the impact of perceived control and coping
      style on childhood homesickness.
AB  - Research on children's coping with homesickness during relatively uncontrollable
      separations has suggested that secondary control coping (i.e., adjusting oneself
      to fit objective conditions) is often preferred over primary control coping
      (i.e., modifying objective conditions to fit oneself). Related research suggests
      that negative affect is associated with (a) relinquishing control or using
      primary control to cope with uncontrollable stressors and (b) perceiving low
      control over stressors. The convergence of these factors was examined for the
      stressor of homesickness. Among 1,032 boys and girls spending 2 weeks at
      residential summer camps, the most frequent and effective way of coping with
      homesickness was to exert secondary control by engaging in a distracting physical
      activity. Contrary to speculation, the use of secondary control coping rose in
      adolescence. Congruent with empirical predictions, the most homesick children
      perceived low control over homesickness and separation, and coped by
      relinquishing control.

PMID- 9149930
TI  - Relation between academic achievement and social adjustment: evidence from
      Chinese children.
AB  - A sample of children in Shanghai, P.R. China, initially aged 10 and 12 years,
      participated in this 2-year longitudinal project. Information on academic
      achievement and indexes of social adjustment, including social competence,
      aggression, social inhibition, leadership, and peer acceptance, was collected
      from multiple sources. It was found that academic achievement predicted
      children's social competence and peer acceptance. In turn, children's social
      functioning and adjustment, including social competence, aggression-disruption,
      leadership, and peer acceptance, uniquely contributed to academic achievement.
      These results generally supported the "reciprocal effects" model concerning the
      relations between academic achievement and social adjustment (S. P. Hinshaw,
      1992).

PMID- 9149931
TI  - Developmental differences in the understanding of and reaction to others'
      inhibition of emotional expression.
AB  - In Study 1,160 individuals from kindergarten (kd), 3rd, 6th, 9th, and college
      grades were presented story protagonists who facially expressed or did not
      express sadness/fear when encountering events that likely caused (relevant
      inhibitory cause) or did not cause (irrelevant cause) the inhibition of the
      expression of emotion. In Study 2, 108 kd, 3rd-, and 6th-grade children viewed
      peers engaging in real interactions similar to the stories. In both studies,
      kindergartners judged that relevant-inhibitory causes decreased a peer's
      emotions. Older individuals displayed an understanding of the inhibition of
      emotional expression by ascribing greater emotion to the peer under relevant
      inhibitory than irrelevant causal conditions. In Study 2, age differences in
      children's search for social information and prosocial behavior paralleled
      judgments of emotion.

PMID- 9149932
TI  - Age and sex differences in dyadic and group interaction.
AB  - This study examined age and sex differences in dyadic and group interaction in a
      standardized setting. Seven classes of 4-year-old children and 6 classes of 6
      year-old children participated. From these classes, 13 male playgroups and 13
      female playgroups were formed. The playgroups were videotaped, and frequencies of
      dyadic and group interaction were tabulated. Results showed that boys and girls
      at both ages engaged in similar frequencies but different patterns of dyadic
      interaction. Only 6-year-old boys, however, interacted in groups. The discussion
      considers the etiology of these age and sex differences.

PMID- 9149933
TI  - Exploring the genetic etiology of low general cognitive ability from 14 to 36
      months.
AB  - The genetic and environmental etiology of low general cognitive ability (g)
      during infancy and early childhood has not previously been investigated. The
      current study examined the genetic etiology of low cognitive ability at 14, 20,
      24, and 36 months with twins from the MacArthur Longitudinal Twin Study. Low g
      groups were formed from the lowest 10th percentile at each age. Univariate
      probandwise concordance rates and DeFries-Fulker (J. C. DeFries & D. W. Fulker,
      1985, 1988) multiple regression techniques suggest genetic etiology in low
      general cognitive ability groups. The stability of low general cognitive ability
      over time also appears to be primarily due to genetic factors. Although
      replication is necessary, these results suggest that the genetic etiology of low
      g during infancy and early childhood is at least as great as the heritability of
      g in the unselected population.

PMID- 9149934
TI  - Developmental changes in speed of information processing in young children.
AB  - This study investigated developmental increases in processing speed in young
      children, relative to adults, with only nonverbal stimuli. R. Kail's (1991) model
      of the rate of change in processing speed from childhood to adulthood was
      evaluated. Processing speed was measured in 34 children at 4 years, 37 at 5
      years, and 38 at 6 years and in 43 adults, with a battery of 8 computer
      administered tests. Results showed clear age-related increases in processing
      speed that cannot be attributed to increased accuracy and error rate monitoring.
      Kail's model adequately accounted for the observed rate of developmental change
      in processing speed; however, the parameter estimates of R. Kail and Y. Park
      (1992) provided more accurate predictions than did the meta-analytically derived
      estimates of Kail (1991). Findings support the global developmental trend
      hypothesis and suggest that this trend extends beyond the range of verbal skills
      evaluated in previous research.

PMID- 9149935
TI  - Challenging the notion of a thematic preference in young children.
AB  - Many researchers have argued that early cognitive development is characterized by
      a conceptual preference for thematic over taxonomic relations. However, more
      recent research indicates that infants and toddlers may not favor thematic
      relations. To resolve this discrepancy, the conceptual preferences of children
      ranging from 2 to 4 years of age were examined, using a forced-choice task
      including a target (e.g., a carrot), a thematic alternative (e.g., a rabbit), and
      a taxonomic alternative (e.g., a tomato). The effects of age, experimenter's
      instructions, hierarchical level (basic vs. superordinate), and stimulus medium
      (pictures vs. objects) were examined systematically. Children revealed no
      pervasive preference for either thematic or taxonomic relations. This challenges
      the notion of a developmental shift in conceptual preferences and suggests a more
      continuous trajectory in early conceptual development.

PMID- 9149936
TI  - Human whole-genome shotgun sequencing.

PMID- 9149937
TI  - Against a whole-genome shotgun.

PMID- 9149938
TI  - Big time for small genomes.

PMID- 9149939
TI  - An STS-based radiation hybrid map of the human genome.
AB  - We have constructed a physical map of the human genome by using a panel of 83
      whole genome radiation hybrids (the Stanford G3 panel) in conjunction with 10,478
      sequence-tagged sites (STSs) derived from random genomic DNA sequences,
      previously mapped genetic markers, and expressed sequences. Of these STSs, 5049
      are framework markers that fall into 1766 high-confidence bins. An additional 945
      STSs are indistinguishable in their map location from one or more of the
      framework markers. These 5994 mapped STSs have an average spacing of 500 kb. An
      additional 4484 STSs are positioned with respect to the framework markers.
      Comparison of the orders of markers on this map with orders derived from
      independent meiotic and YAC STS-content maps indicates that the error rate in
      defining high-confidence bins is < 5%. Analysis of 322 random cDNAs indicates
      that the map covers the vast majority of the human genome. This STS-based
      radiation hybrid map of the human genome brings us one step closer to the goal of
      a physical map containing 30,000 unique ordered landmarks with an average marker
      spacing of 100 kb.

PMID- 9149940
TI  - A linkage map of the rat genome derived from three F2 crosses.
AB  - We report the construction of a dense linkage map of the rat genome integrating
      767 simple sequence length polymorphism markers, combined over three crosses with
      high rates of polymorphism. F2 populations from WKY x S (n = 159), BN x S (n =
      91), and BN x GK (n = 139) were selected and genotyped for combinations of
      microsatellite markers. The loci define 21 linkage groups corresponding to the 20
      rat autosomal chromosomes and the X chromosome. The map spans a genetic length of
      1998 cM. This combined linkage map should facilitate the advancement of genetic
      studies for a wide variety of rat models characterized for complex phenotypes.

PMID- 9149941
TI  - A 1.1-Mb transcript map of the hereditary hemochromatosis locus.
AB  - In the process of positionally cloning a candidate gene responsible for
      hereditary hemochromatosis (HH), we constructed a 1.1-Mb transcript map of the
      region of human chromosome 6p that lies 4.5 Mb telomeric to HLA-A. A combination
      of three gene-finding techniques, direct cDNA selection, exon trapping, and
      sample sequencing, were used initially for a saturation screening of the 1.1-Mb
      region for expressed sequence fragments. As genetic analysis further narrowed the
      HH candidate locus, we sequenced completely 0.25 Mb of genomic DNA as a final
      measure to identify all genes. Besides the novel MHC class 1-like HH candidate
      gene HLA-H, we identified a family of five butyrophilin-related sequences, two
      genes with structural similarity to a type 1 sodium phosphate transporter, 12
      novel histone genes, and a gene we named RoRet based on its strong similarity to
      the 52-kD Ro/SSA lupus and Sjogren's syndrome auto-antigen and the RET finger
      protein. Several members of the butyrophilin family and the RoRet gene share an
      exon of common evolutionary origin called B30-2. The B30-2 exon was originally
      isolated from the HLA class 1 region, yet has apparently "shuffled" into several
      genes along the chromosome telomeric to the MHC. The conservation of the B30-2
      exon in several novel genes and the previously described amino acid homology of
      HLA-H to MHC class 1 molecules provide further support that this gene-rich region
      of 6p21.3 is related to the MHC. Finally, we performed an analysis of the four
      approaches for gene finding and conclude that direct selection provides the most
      effective probes for cDNA screening, and that as much as 30% of ESTs in this 1.1
      Mb region may be derived from noncoding genomic DNA.

PMID- 9149942
TI  - Clone-contig and STS maps of the hereditary hemochromatosis region on human
      chromosome 6p21.3-p22.
AB  - YAC-based and bacterial-clone based STS-content maps were constructed that served
      as the framework physical maps for the positional cloning of a candidate gene for
      hereditary hemochromatosis. The YAC-based map comprises 43 YACs and 86 STS and
      spans approximately 8 Mb of DNA between the class I region of the major
      histocompatibility complex on human chromosome 6p21.3 and D6S276 in 6p22.
      Comparison with published maps revealed a hole in the MIT/Whitehead and CEPH YAC
      maps that includes the immediate region around the hemochromatosis gene itself.
      Approximately 3 Mb of DNA was covered by a bacterial clone contig that consists
      of 38 BACs, 45 PACs, 26 PI clones and one lambda phage. The bacterial clone-based
      STS map comprises 153 STSs. A contiguous block of 8 STSs could be amplified from
      both human chromosome 6 and 5. Further characterization of selected STSs and
      bacterial clones by radiation hybrid mapping and fluorescence in situ
      hybridization, respectively, revealed the presence of a multicopy DNA segment,
      more than one bacterial clone length in size, which is duplicated near the
      chromosome-6 centromere and part of which is present in multiple copies on
      chromosome 5. Possible implications of the incomplete public YAC-contig map and
      of the multicopy segment for physical mapping and linkage disequilibrium studies
      of the hemochromatosis candidate region are discussed.

PMID- 9149943
TI  - Low frequency of microsatellites in the avian genome.
AB  - A better insight into the occurrence of microsatellites in a range of taxa may
      help to understand the evolution of simple repeats. Previous studies have found
      the relative abundance of several repeat motifs to differ among mammals,
      invertebrates, and plants. Absolute numbers of microsatellites also tend to
      correlate positively with genome size. We analyzed the occurrence, frequency, and
      distribution of microsatellites in birds, a taxon with one of the smallest known
      genome sizes among vertebrates. Dot-blot hybridization revealed that about half
      of 22 different di-, tri-, and tetranucleotide repeat motifs were clearly more
      common in human than in three species of birds: chicken, woodpecker, and swallow.
      For the remaining motifs no clear difference was found. From searching avian
      database sequences we estimated there to be 30,000-70,000 microsatellites longer
      than 20 bp in the avian genome. The number of (CA) > or = 10 would be around 7000
      9000 and the number of (CA) > or = 14 about 3000. The calculated density of avian
      microsatellites (total, one every 20-39 kb; (CA) > or = 10, one every 136-150 kb)
      is much lower than that estimated for the human genome (one every 6 and 30 kb,
      respectively). This may be explained by the fact that the avian genome contains
      relatively less noncoding DNA than most mammals and that avian SINE/LINE elements
      do not terminate in poly(A) tails, which are known to provide a resource for the
      evolution of simple repeats in mammals. We found no association between
      microsatellites and SINEs in birds. Primed in situ labeling suggested fairly even
      distribution of (CA)n repeats over chicken macrochromosomes and intermediate
      chromosomes, whereas the microchromosomes, a large part of the Z and W
      chromosomes, and most telomeres and centromeres had very low concentrations of
      (CA)n microsatellites. The scarcity of microsatellites on the microchromosomes is
      compatible to these regions likely being unusually rich in coding sequences. The
      low microsatellite density in the genome in general and on the microchromosomes
      in particular imposes an obstacle for the development of marker-rich genetic maps
      of chicken and other birds, and for the localization of quantitative trait genes.

PMID- 9149944
TI  - Fine localization of the torsion dystonia gene (DYT1) on human chromosome 9q34:
      YAC map and linkage disequilibrium.
AB  - The DYT1 gene, which maps to chromosome 9q34, appears to be responsible for most
      cases of early-onset torsion dystonia in both Ashkenazic Jewish (AJ) and non
      Jewish families. This disease is inherited in an autosomal dominant mode with
      reduced penetrance (30%-40%). The abnormal involuntary movements associated with
      this disease are believed to be caused by unbalanced neural transmission in the
      basal ganglia. Previous linkage disequilibrium studies in the AJ population
      placed the DYT1 gene in a 2-cM region between the loci D9S62a and ASS. A YAC
      contig has now been created spanning 600 kb of this region including D9S62a. The
      location of the DYT1 gene has been refined within this contig using several new
      polymorphic loci to expand the linkage disequilibrium analysis of the AJ founder
      mutation. The most likely location of the DYT1 gene is within a 150 kb region
      between the loci D9S2161 and D9S63.

PMID- 9149945
TI  - Computational and biological analysis of 680 kb of DNA sequence from the human
      5q31 cytokine gene cluster region.
AB  - With the human genome project advancing into what will be a 7- to 10-year DNA
      sequencing phase, we are presented with the challenge of developing strategies to
      convert genomic sequence data, as they become available, into biologically
      meaningful information. We have analyzed 680 kb of noncontiguous DNA sequence
      from a 1-Mb region of human chromosome 5q31, coupling computational analysis with
      gene expression studies of tissues isolated from humans as well as from mice
      containing human YAC transgenes. This genomic interval has been noted previously
      for containing the cytokine gene cluster and a quantitative trait locus
      associated with inflammatory diseases. Our analysis identified and verified
      expression of 16 new genes, as well as 7 previously known genes. Of the total of
      23 genes in this region, 78% had similarity matches to sequences in protein
      databases and 83% had exact expressed sequence tag (EST) database matches.
      Comparative mapping studies of eight of the new human genes discovered in the
      5q31 region revealed that all are located in the syntenic region of mouse
      chromosome 11q. Our analysis demonstrates an approach for examining human
      sequence as it is made available from large sequencing programs and has resulted
      in the discovery of several biomedically important genes, including a cyclin, a
      transcription factor that is homologous to an oncogene, a protein involved in DNA
      repair, and several new members of a family of transporter proteins.

PMID- 9149946
TI  - A differential hybridization scheme to identify photoreceptor-specific genes.
AB  - Identification of genes expressed preferentially or exclusively in photoreceptors
      will facilitate the understanding of photoreceptor biology as well as provide
      candidate genes for inherited retinal degenerations. To achieve this goal we
      performed a differential hybridization screen of 3717 well-isolated phage clones
      from a human retinal cDNA library. Clones were selected for further study if they
      hybridized exclusively or strongly preferentially to a probe derived from RNA
      isolated from the cone-predominant retina of 13-line ground squirrels as compared
      to a probe derived from human fibroblast RNA. Twenty percent of clones (9/45)
      identified by this screen were derived from photoreceptor-specific genes and an
      additional 24.4% (11/45) were from neural-specific genes, demonstrating the
      utility of this strategy in identifying genes important for retinal biology.

PMID- 9149947
TI  - The organization of the gamma-glutamyl transferase genes and other low copy
      repeats in human chromosome 22q11.
AB  - A clone map consisting of YACs, cosmids, and fosmids has been constructed
      covering low copy repeat regions of human chromosome 22q11. A combination of
      clone restriction digest analysis, single-copy landmark content analysis, HindIII
      Sau3AI fingerprinting, and sequencing of PCR products derived from clones was
      required to resolve the map in this region. Seven repeat-containing contigs were
      placed in 22q11, five containing gamma-glutamyl transferase (GGT) sequences
      described previously. In one case, a single interval at the resolution of the YAC
      map was shown to contain at least three GGT sequences after higher resolution
      mapping. The sequence information was used to design a rapid PCR/restriction
      digest technique that distinguishes the GGT loci placed in the YAC map. This
      approach has allowed us to resolve the previous cDNA and mapping information
      relating to GGT and link it to the physical map of 22q11.

PMID- 9149948
TI  - The human homolog of a mouse-imprinted gene, Peg3, maps to a zinc finger gene
      rich region of human chromosome 19q13.4.
AB  - Peg3 (paternally expressed gene 3) is the first imprinted gene detected in the
      proximal region of mouse chromosome 7. Because imprinting is a trait that is
      generally conserved among mammals, and imprinted domains generally encompass
      several adjacent genes, expression patterns and chromosomal environment of the
      human counterpart of Peg3 are of special interest. In this study we have
      localized human PEG3 approximately 2 Mb proximal of the telomere of chromosome
      19q, within a region known to carry large numbers of tandemly clustered Kruppel
      type zinc finger-containing (ZNF) genes. Peg3 also encodes a Kruppel-type ZNF
      protein but one that is distinguished from other ZNF gene products by the fact
      that it carries two novel proline-rich motifs. Comparison between mouse Peg3 and
      partial human PEG3 gene sequences revealed a high level of conservation between
      the two species, despite the fact that one of the two proline-rich repeats is
      absent from the human gene. Our data demonstrate that the human gene is expressed
      at highest levels in ovary and placenta; mouse Peg3, by contrast, is transcribed
      at highest levels in the adult brain. These comparative mapping, sequencing, and
      expression data provide the first clues to the potential activities of PEG3, and
      generate new tools to aid in the analysis of structure and function of a
      potentially new imprinted domain located in human chromosome 19q13.4 and mouse
      chromosome 7.

PMID- 9149949
TI  - Sequence mapping by electronic PCR.
AB  - The highly specific and sensitive PCR provides the basis for sequence-tagged
      sites (STSs), unique landmarks that have been used widely in the construction of
      genetic and physical maps of the human genome. Electronic PCR (e-PCR) refers to
      the process of recovering these unique sites in DNA sequences by searching for
      subsequences that closely match the PCR primers and have the correct order,
      orientation, and spacing that they could plausibly prime the amplification of a
      PCR product of the correct molecular weight. A software tool was developed to
      provide an efficient implementation of this search strategy and allow the sort of
      en masse searching that is required for modern genome analysis. Some sample
      searches were performed to demonstrate a number of factors that can affect the
      likelihood of obtaining a match. Analysis of one large sequence database record
      revealed the presence of several microsatellite and gene-based markers and
      allowed the exact base-pair distances among them to be calculated. This example
      provides a demonstration of how e-PCR can be used to integrate the growing body
      of genomic sequence data with existing maps, reveal relationships among markers
      that existed previously on different maps, and correlate genetic distances with
      physical distances.

PMID- 9149951
TI  - Training in firearm safety counseling in family practice residency programs.
AB  - The purpose of this study was to establish a national baseline regarding the
      prevalence of training of family practice residents regarding firearm safety
      counseling. A national survey of the residency directors at the 420 accredited
      family practice residency programs in the coterminous United States was used to
      assess the prevalence of training in firearm safety counseling, perceived
      effectiveness of such training, and perceived barriers to such counseling in
      residency programs. Program directors were sent a two-page questionnaire on
      firearm safety counseling activity in their programs and 71% responded. Few
      residencies (16%) had formal training in firearm safety counseling. The most
      common perceived barriers were no trained personnel (31%), too many other
      important issues (31%), not enough time (30%), and lack of educational resources
      (28%). Patient education materials (57%), video training programs (49%), and a
      curriculum guide (46%) were identified as resources that would be most helpful in
      implementing a firearm safety counseling program. The results showed that formal
      training in firearm safety counseling is virtually absent from family practice
      residency training programs. This finding is not surprising given that less than
      14% of the directors perceived firearm safety counseling would be effective in
      reducing firearm-related injuries or deaths and that research on effectiveness of
      such counseling is very limited.

PMID- 9149950
TI  - A transposon-based strategy for sequencing repetitive DNA in eukaryotic genomes.
AB  - Repetitive DNA is a significant component of eukaryotic genomes. We have
      developed a strategy to efficiently and accurately sequence repetitive DNA in the
      nematode Caenorhabditis elegans using integrated artificial transposons and
      automated fluorescent sequencing. Mapping and assembly tools represent important
      components of this strategy and facilitate sequence assembly in complex regions.
      We have applied the strategy to several cosmid assembly gaps resulting from
      repetitive DNA and have accurately recovered the sequences of these regions.
      Analysis of these regions revealed six novel transposon-like repetitive elements,
      IR-1, IR-2, IR-3, IR-4, IR-5, and TR-1. Each of these elements represents a
      middle-repetitive DNA family in C. elegans containing at least 3-140 copies per
      genome. Copies of IR-1, IR-2, IR-4, and IR-5 are located on all (or most) of the
      six nematode chromosomes, whereas IR-3 is predominantly located on chromosome X.
      These elements are almost exclusively interspersed between predicted genes or
      within the predicted introns of these genes, with the exception of a single IR-5
      element, which is located within a predicted exon. IR-1, IR-2, and IR-3 are
      flanked by short sequence duplications resembling the target site duplications of
      transposons. We have established a website database
      (http:(/)/www.welch.jhu.edu/approximately devine/RepDNAdb.html) to track and
      cross-reference these transposon-like repetitive elements that contains detailed
      information on individual element copies and provides links to appropriate
      GenBank records. This set of tools may be used to sequence, track, and study
      repetitive DNA in model organisms and humans.

PMID- 9149952
TI  - The extent of barriers and linkages to health care for head start children.
AB  - Data were gathered as part of a larger survey of 218 Head Start Programs in
      Region II (New York City, New York State (excluding New York City), New Jersey,
      Puerto Rico and U.S. Virgin Islands) in 1993-94. The general purpose of the
      survey was to obtain information on child health, screening practices, training
      needs, family health and community problems, barriers to diagnosis and treatment
      and the extent of linkages between Head Start programs and health and nutrition
      providers at the local level. In this study barriers to the care of Head Start
      children and their families were examined as perceived by the Health Coordinators
      or other health related staff of the Health Services Component of these programs.
      The extent of linkages with health and nutrition service providers were also
      examined. The most frequently reported barriers were lack of parent participation
      (72%), private transportation not available (67%), parents' perception of quality
      of care (64%), distance to provider (63%), cost of transportation (63%), lack of
      funding (56%), limited/inconvenient hours (56%), and health services not
      available in the community (55%). On average, programs reported linkages to 14.5
      providers (including an average of 4 nutrition programs). More than 90% of them
      reported linkages with public health services, child protective services, WIC and
      private physicians/dentists. Finally, the extent of barriers and linkages were
      compared across different geographic areas. Significant barriers were identified
      in this study, yet the survey confirmed and validated the extensive nature of
      formal linkages with health and nutrition service providers at the local levels.
      These findings may indicate that the current levels of service availability may
      not be sufficient to meet the severity and diversity of health needs of this
      population.

PMID- 9149954
TI  - Developing and evaluating a Spanish TEL-MED message on breast cancer.
AB  - A Spanish TEL-MED message on breast cancer was designed for Delaware. The
      message, created from a focus group of Latino professionals and volunteers from
      the American Cancer Society, Delaware Division, provides information for Latinas
      on breast cancer. In one minute, forty-five seconds the message answers in
      Spanish the following questions: (1) What are the symptoms of breast cancer? (2)
      What can women do to protect themselves against breast cancer? (3) What is a
      mammogram? (4) When should I have a mammogram done? (5) How much does a mammogram
      cost? The message also provides information on where to obtain low cost or free
      mammograms. A pamphlet in Spanish, featuring a picture of an elderly Latina
      listening to the phone message, describes how to access the tape. The message
      targets older Latinas who prefer to speak Spanish. The American Cancer Society,
      Delaware Division, distributed a press release featuring the Spanish TEL-MED and
      circulated the pamphlets to Latino organizations and churches. Evaluation of the
      TEL-MED message in Spanish suggests it to be an innovative way to reach older
      Latino women. The Spanish message on breast cancer was requested 58% as often as
      the breast cancer message in English, and 193% more often than the epilepsy tape
      in Spanish. The peak period for the calls to the Spanish TEL-MED message occurred
      after the initial promotional activities. These findings suggest that education
      of older Latinas on breast cancer can be augmented by the use of TEL-MED message
      in Spanish. They further suggest that the combination of TEL-MED and mass media
      campaign had a positive effect on Spanish speaking users of the TEL-MED.

PMID- 9149953
TI  - Prevalence and predictors of tobacco use among Lumbee Indian women in Robeson
      County, North Carolina.
AB  - Tobacco use among some Native American tribes is high compared to the overall US
      population. Little is known, however, about tobacco use among Native Americans in
      North Carolina, a state with strong economic ties to tobacco. To assess the
      epidemiology of tobacco use in this population, data from the North Carolina
      Native American Cervical Cancer Project was reviewed. Nine hundred eighty-two
      Lumbee Indian women in Robeson County provided general demographic information as
      well as information on cancer risk knowledge, attitudes and behaviors during the
      5-year study. Women were selected from the community using a random sample of
      5200 persons from the tribal roll of approximately 40,000 persons. 20.6% of women
      were current smokeless tobacco users, while 23.7% were current smokers.
      Demographic and social support predictors were unique for the different types of
      tobacco use. Cigarette smoking was associated with younger age, higher education,
      excellent or good self-reported health, having a recent physical exam, separated
      or divorced marital status, low church participation, and alcohol consumption.
      Conversely, use of smokeless tobacco was associated with older age, lower
      education level, fair or poor self-reported health, widowed marital status, and
      having a high number of friends. These data show a high prevalence of smokeless
      tobacco use among women in this population, and a contrast in the predictors of
      tobacco use by source. Intervention programs for tobacco use cessation should be
      sensitive to these differences.

PMID- 9149955
TI  - Preventing teen pregnancy through persuasive communications: realities, myths,
      and the hard-fact truths.
AB  - Effective campaigns are desperately needed to combat the serious social problem
      of teen pregnancy. However, public health campaigns are most often noted for
      failures, rather than successes. One reason for a campaign failing to have the
      intended effect is lack of theoretical guidance at the formative evaluation
      stage. The study reported here is a theoretically-based formative evaluation with
      inner city teens. Six focus groups were conducted to determine knowledge,
      attitudes, beliefs, and recommendations for effective campaigns to deter teen
      pregnancy. The results indicate that campaign messages need to combat positive
      attitudes toward pregnancy, negative attitudes toward birth control, the
      perception of personal invulnerability, and emphasize the negative consequences
      of sexual intercourse. This study's findings also suggest that campaigns with
      these messages need to start at an early age in order to effectively prevent teen
      pregnancy.

PMID- 9149957
TI  - Structural studies on casein micelles of human milk: dissociation of beta-casein
      of different phosphorylation levels induced by cooling and
      ethylenediaminetetraacetate.
AB  - Information on the structure of human casein micelles has been obtained from
      dissociation of beta-casein (CN). Two approaches were used: cooling at 4 degrees
      C and addition of EDTA. An initial loss of about 80% of the protein optical
      density occurred upon cooling to 4 degrees C. Dissociation was time dependent,
      and at > or = 24 h about 10% remained. However, mean size and voluminosity of
      micelles increased, as indicated by laser light scattering and viscosity
      measurements. This process was reversible, and 95% of the protein reentered the
      micelles upon incubation for 3 h at 37 degrees C. Upon cooling, amounts of
      nonphosphorylated beta-CN increased, and singly phosphorylated beta-CN levels
      were almost constant relative to the total beta-CN in micelles. Upon addition of
      EDTA (0 to 5 mM), the forms with three to five phosphates were the major
      dissociating constituents; EDTA that was added by dialysis produced similar
      results but at lower concentrations. These data suggest that, in the absence of
      significant amounts of alpha s1-CN, nonphosphorylated and singly phosphorylated
      human beta-CN may form a framework, as proposed for alpha s1-CN for bovine milk,
      along with the colloidal calcium phosphate for the development of the final
      micelle structure by addition of the more highly phosphorylated forms. The
      results also indicate that human casein micelles have a less rigid structure than
      those of other species.

PMID- 9149956
TI  - Characterization of phosphate sites in native ovine, caprine, and bovine casein
      micelles and their caseinomacropeptides: a solid-state phosphorus-31 nuclear
      magnetic resonance and sequence and mass spectrometric study.
AB  - The phosphate sites in native ovine, caprine, and bovine casein micelles have
      been analyzed using sequence analysis, mass spectrometric analysis, and solid
      state 31P nuclear magnetic resonance spectroscopy. Using a combination of S
      ethylcysteine derivatization, sequence analysis, and mass spectrometric analysis,
      the phosphorylation sites of ovine (SerP151 and SerP168), caprine (SerP151 and
      SerP168), and bovine (SerP149) caseinomacropeptides have been localized. Various
      solid-state 31P methods using magic angle spinning have been applied to ascertain
      the local structure and dynamics of the phosphorylated serine residues and the
      inorganic calcium phosphates within the micelles. Contributions from the
      phosphorylated serine residues of kappa-CN, located in the C-terminal portion of
      the molecule, to the mobile constituents of the micelles were assigned by
      comparison with 31P nuclear magnetic resonance spectra of purified
      caseinomacropeptides from the various species in the dissolved state. Comparison
      of the 31P magic angle spinning nuclear magnetic resonance spectra of ovine,
      caprine, and bovine casein micelles indicates that the micelles from these
      species are very similar but not identical.

PMID- 9149958
TI  - Comparative effects of recombinant ovine placental lactogen and bovine growth
      hormone on galactopoiesis in ewes.
AB  - The effects of recombinant ovine placental lactogen and bovine growth hormone on
      milk yield, milk composition, and concentrations of blood hormones and
      metabolites were compared in ewes during an established lactation. Beginning on d
      17 of lactation, ewes were treated for 5 d with twice daily subcutaneous
      injections of ovine placental lactogen (n = 9), bovine growth hormone (n = 10) at
      a dose of 0.10 mg/d per kg of body weight, or saline (n = 10). Circulating
      concentrations of ovine placental lactogen were 24.6 +/- 1.6 ng/ml on d 5 for
      ewes treated with ovine placental lactogen, but concentrations of ovine placental
      lactogen were undetectable in ewes treated with either saline or bovine growth
      hormone. Treatment with bovine growth hormone increased circulating
      concentrations of growth hormone, insulin-like growth factor-I, and nonesterified
      fatty acids and decreased urea concentrations relative to those in ewes treated
      with ovine placental lactogen or saline. Compared with saline treatment, no
      parameters were affected by treatment with ovine placental lactogen. Treatment
      with bovine growth hormone or ovine placental lactogen treatment had no
      significant effects on plasma concentrations of insulin, glucose, or creatinine.
      Treatment with bovine growth hormone, but not ovine placental lactogen, increased
      yields of milk, fat, and lactose. Weight of the mammary gland was increased by
      bovine growth hormone, but not by ovine placental lactogen. Despite the fact that
      ovine placental lactogen is a potent somatogen, it does not appear to exhibit the
      same galactopoietic activity as bovine growth hormone in lactating ewes.

PMID- 9149959
TI  - Effects of fatty acids and hormones on fatty acid metabolism and gluconeogenesis
      in bovine hepatocytes.
AB  - Primary cultures of hepatocytes were used to study the effects of extracellular
      oleate concentration and hormones on fatty acid metabolism and gluconeogenesis.
      Rates of oleate uptake and oxidation to acid-soluble products varied linearly as
      oleate concentrations increased (0.1 to 2 mM), but rates of triglyceride
      accumulation varied quadratically. Insulin increased the proportion of oleate
      that was esterified by 22% without affecting the formation of acid-soluble
      products. Cells incubated with 2 mM [1-(14)C]oleate for 24 h eliminated 9.6% of
      the labeled intracellular lipid as acid-soluble products in the following 24 h
      when no oleate was present during depletion and eliminated 7.7% when 2 mM oleate
      was present. Insulin reduced labeled triglyceride depletion by 49%.
      Gluconeogenesis from [2-(14)C] propionate was depressed by 24%, and formation of
      acid-soluble products was increased by 46% in cells infiltrated with lipid
      because of previous exposure to 2 mM oleate for 45 h. Rates of gluconeogenesis
      from propionate were reduced 23% when 2 mM oleate was present during the 3-h
      period that gluconeogenesis was measured, and the effect was not modified by
      lipid infiltration. Lipid infiltration influenced hepatic function, and insulin
      regulated hepatic triglyceride concentration.

PMID- 9149960
TI  - Hepatic gene expression of apolipoprotein B100 during early lactation in
      underfed, high producing dairy cows.
AB  - The hepatic gene expression of apolipoprotein B, the major protein of very low
      density lipoproteins in plasma, was studied using 8 Holstein x Friesian cows
      during the first 12 wk of lactation. Cows were fattened during gestation and were
      underfed just after parturition to increase fat mobilization and subsequent
      hepatic steatosis. Intracellular concentrations of apolipoprotein B and
      apolipoprotein B mRNA and control parameters (albumin, total lipids, RNA, and
      proteins) were determined in liver samples obtained by biopsy from each cow on
      four occasions at 1, 2, 4, and 12 wk after calving. Results were compared with
      those obtained from 5 dry cows in late pregnancy and 4 dry nonpregnant cows. The
      hepatic concentration of apolipoprotein B was lower (approximately 25%) during wk
      1, 2, and 4 after calving, a period of intense liver steatosis (44.2 to 95.7 mg
      of triglycerides/g of fresh tissue), than for nonsteatotic dry cows (pregnant or
      nonpregnant); hepatic concentrations were also lower than those during wk 12. In
      contrast, hepatic concentrations of mRNA coding for apolipoprotein B, total
      proteins, RNA, and albumin did not vary significantly during early lactation.
      These results suggested that synthesis of apolipoprotein B during early lactation
      is specifically regulated at a posttranscriptional level by a decrease in the
      rate of translation, or by a higher rate of intracellular degradation of
      apolipoprotein B, or both.

PMID- 9149961
TI  - Antibacterial peptides of bovine lactoferrin: purification and characterization.
AB  - Three peptides with antibacterial activity toward enterotoxigenic Escherichia
      coli have been purified from a pepsin digest of bovine lactoferrin. All peptides
      were cationic and originated from the N-terminus of the molecule in a region
      where a bactericidal peptide, lactoferricin B, had been previously identified.
      The most potent peptide, peptide I, was almost identical to lactoferricin B; the
      sequence corresponded to residues 17 to 42, and the molecular mass was 3195 as
      determined by mass spectrometry. A second, less active peptide, peptide II,
      consisted of two sequences, residues 1 to 16 and 43 to 48 (molecular mass of
      2673), linked by a single disulfide bond. The third peptide, peptide III, also a
      disulfide-linked heterodimer, corresponded to residues 1 to 48 (molecular mass of
      5851), cleaved between residues 42 and 43. Peptides I and II displayed
      antibacterial activity toward a number of pathogenic and food spoilage
      microorganisms, and peptide I inhibited the growth of Listeria monocytogenes at
      concentrations as low as 2 microM. Bacterial growth curves showed that
      bactericidal effects of peptides I and II were observable within 30 min of
      exposure. The results confirmed and extended those of earlier studies suggesting
      that the bactericidal domain of lactoferrin was localized in the N-terminus and
      did not involve iron-binding sites.

PMID- 9149962
TI  - Replacement of alfalfa neutral detergent fiber with a combination of nonforage
      fiber sources.
AB  - Sixteen Holstein cows in midlactation were used in a 4 x 4 Latin square design to
      determine the effect of replacing alfalfa neutral detergent fiber (NDF), with NDF
      from a combination of whole linted cottonseed, dried distillers grains, and wheat
      middlings. The four diets were a basal control diet that was low in forage and
      fiber [(5.9 g of corn silage NDF and 6.1 g of alfalfa NDF/100 g of dry matter
      (DM)], a normal forage diet (low forage plus 10 g of additional alfalfa NDF/100 g
      of DM), and two low forage diets with either 5 or 10 g of NDF from the nonforage
      fiber sources added per 100 g of DM. Milk yield, milk protein yield, and milk
      protein percentage were higher, and milk fat percentage and fat yield were lower,
      for cows fed the low forage diets than for those fed the alfalfa control diet
      that was higher in fiber. Among the low forage diets, dry matter intake, milk fat
      percentage, and fat yield all increased linearly as NDF content increased. The
      ratio of acetate to propionate in the rumen and rumination times were greater for
      the normal forage control diet than for the high nonforage fiber diet. Added NDF
      from these nonforage fiber sources increased milk fat percentage and yield, but
      this increase was less than the NDF from alfalfa and less than predicted. In
      agreement with results of similar previous trials, milk protein yield and
      percentage were increased when alfalfa NDF was replaced with fiber from nonforage
      fiber sources.

PMID- 9149963
TI  - Influence of level of concentrate allocation and fermentability of forage fiber
      on chewing behavior and production of dairy cows.
AB  - Nine midlactation dairy cows were offered one of three mixed silage rations with
      neutral detergent fiber (NDF) that was similar in concentration but different in
      fermentability. Differences in fermentability were achieved by substituting a
      high quality alfalfa silage for a low quality alfalfa silage and substituting a
      combination of ryegrass and timothy silages for a barley silage. In addition,
      concentrate was allocated at 0.30, 0.82, or 1.37 kg of dry matter/kg of dry
      matter intake (DMI) from the mixed silage ration. As expected, the NDF content of
      the mixed silage ration did not differ, although fermentability of NDF increased
      numerically as forage quality increased. Intake of NDF increased linearly, and
      DMI tended to increase linearly, as fiber fermentability of the mixed silage
      ration increased. In addition, cows produced more milk, milk fat, and milk
      protein and generated more total and milk energy. The calculated concentration of
      net energy for lactation of the total diet also increased. Results support the
      concept that NDF quality influences and can be used to predict voluntary feed
      intake, at least in relatively high producing dairy cows. The DMI increased, and
      intake of NDF and crude protein declined, as the allocation of concentrate
      increased. In addition, as concentrate allocation increased, cows spent less time
      eating and ruminating and more time resting and produced more milk, milk protein,
      and milk lactose. Cows also generated more total energy and milk energy,
      although, despite a sharp decrease in the forage proportion of the diet, the
      calculated energy density of the diet did not differ among concentrate levels.
      The lack of significant interactions between concentrate level and fiber
      fermentability for any parameter measured supports the contention that high
      quality forage is critical to a successful dairy ration, regardless of the
      proportion of forage in the diet.

PMID- 9149964
TI  - Protein degradation in response to spontaneous heating in alfalfa hay by in situ
      and ficin methods.
AB  - Alfalfa forage, field-wilted to 29.9 or 19.7% moisture and packaged in five
      baling treatments (prestorage control; conventional bales; and laboratory bales
      made at 1.0, 1.5, and 2.0 times the density of conventional bales), was evaluated
      for protein degradation characteristics by in situ and ficin assays.
      Relationships between degradation rates and accumulated heating degree days
      suggested that these degradation rates are controlled by two conditions.
      Degradation rates increased concurrently with conservation and minimal heating,
      primarily because of a large redistribution of highly degradable N that was
      soluble in prestorage controls, but not in conserved hays. For both methods, this
      effect appeared to be maximized between 100 and 125 heating degree days. With
      respect to the in situ method, these effects appeared to be less pronounced, and
      degradabilities were not affected. After bales accumulated about 125 heating
      degree days, degradation rates decreased predictably in response to heating by
      both methods, as did N degradabilities calculated from in situ data. Increases in
      degradation rates concurrent with conservation and minimal heating appear to be
      especially important considerations when results of the ficin assay are being
      interpreted.

PMID- 9149965
TI  - Effect of processed grain sorghum and expeller soybean meal on performance of
      lactating cows.
AB  - Forty-four Holstein cows were used to measure milk production responses to dry
      rolled versus pelleted grain sorghum and expeller versus solvent soybean meal in
      a 2 x 2 factorial arrangement of treatments. Pelleted grain sorghum was processed
      by grinding, increasing moisture to 31%, extruding, and drying to an exist
      temperature of 93 degrees C. Grain sorghum was included in the diets at 27% of
      dry matter, and soybean meal was the primary source of supplemental protein. Few
      interactions were observed between the methods of processing grain sorghum and
      sources of soybean meal. Pelleting of grain sorghum decreased dry matter intake
      5%, but increased milk production 3%, protein yield 4%, and efficiency 7%; fat
      yield was unaffected. Replacement of solvent soybean meal with expeller soybean
      meal had little effect on intake, but increased milk production 3%, fat yield 5%,
      and efficiency 4%; protein yield was unaffected. Plasma concentrations of amino
      acids (AA) were increased by pelleted grain sorghum and by expeller soybean meal
      at 5 and 10 wk after initiation of treatment, indicating that both of these
      treatments increased the supply of AA to the intestine. Pelleting improved the
      nutritive value of grain sorghum for lactating cows. Although total milk
      production and fat yield increased in response to expeller soybean meal, the lack
      of response in protein yield to this increased supply of RUP indicated that the
      effect was not solely due to an increased supply of AA to the intestine.

PMID- 9149966
TI  - Lactational performance of cows fed low or high ruminally undegradable protein
      prepartum and supplemental methionine and lysine postpartum.
AB  - Multiparous Holstein cows (n = 24) were fed diets containing 34 or 41% ruminally
      undegradable protein (RUP) for 30 d before parturition; then each group was fed a
      basal diet supplemented with or without ruminally stable Met (10.6 g/d) and Lys
      (15.2 g/d) for 75 d in the subsequent lactation. Supplementation of Met and Lys
      increased the milk yield of cows previously fed the low RUP diet, but milk yields
      before and after amino acid (AA) supplementation were similar for cows previously
      fed the high RUP diet. Milk protein content (percentage) increased from 2.83 to
      2.96 for cows previously fed the high RUP diet. Milk protein yield increased from
      1.13 to 1.21 kg/d when Met and Lys were fed. Data on AA concentration in plasma
      and AA extraction by the mammary gland suggest that the supplementation of Met
      and Lys corrected a Met limitation. According to the Cornell Net Carbohydrate and
      Protein System, the lactation diet was limiting for Met for maximum milk yield
      and was corrected by AA supplementation. Based on limiting AA, allowable milk
      yield was 42.5 kg/d, and the observed yield was 40.9 kg/d averaged across
      treatments. The group with the greatest allowable milk yield (45.2 kg/d) had the
      greatest actual milk yield (43.0 kg/d). The regression equation of observed milk
      yield on allowable milk yield was Y = 3.4 + 0.8805X.

PMID- 9149967
TI  - Effects of energy and protein allowances in the diets of prepubertal heifers on
      growth and milk production.
AB  - Sixty-one Italian Friesian heifers between 100 and 300 kg of body weight (BW)
      were fed one of four diets. Heifers that were fed the diet with low energy and
      low protein received 90% of the amounts of total digestible nutrients (TDN) and
      crude protein (CP) recommended by the National Research Council for large breed
      dairy heifers growing at a rate of 0.7 kg/d. Ninety and 110% of recommended
      amounts of TDN and CP, respectively, were supplied to heifers fed the diet
      containing low energy and high protein. The diet with high energy and low protein
      provided 110 and 90% of recommended amounts of TDN and CP, respectively, and
      heifers fed high energy and high protein received 110% of the recommended amounts
      of both TDN and CP. When heifers reached 300 kg of BW, all were fed an identical
      diet. Heifers were bred at approximately 370 kg of BW. The increase of either TDN
      or CP improved average daily gain (608.1 g/d for heifers fed the low energy and
      low protein diet; 658.9 g/d for heifers fed the low energy and high protein diet;
      794.4 g/d for heifers fed the high energy and low protein diet; and 847.6 g/d for
      heifers fed the high energy and high protein diet). Milk production through 36 wk
      of the first lactation was not influenced by the increased TDN or CP in the diet
      (22.7 kg/d for heifers fed low energy and low protein, 22.2 kg/d for heifers fed
      low energy and high protein diet, 20.2 kg/d for heifers fed the high energy and
      low protein diet, and 21.8 kg/d for heifers fed high energy and high protein
      diet). Results showed that Italian Friesian heifers can tolerate an average daily
      gain of approximately 800 g from 100 to 300 kg of BW without any detrimental
      effect on future milk production.

PMID- 9149968
TI  - Effect of volatile fatty acid infusion on development of the rumen epithelium in
      neonatal sheep.
AB  - The purpose of this study was to determine whether the continuous intraruminal
      infusion of calculated physiological concentrations of volatile fatty acids (VFA)
      stimulated the metabolic development of the neonatal rumen. Eight 1-wk-old lambs
      were assigned to one of three treatments: saline infusion (three lambs), VFA
      infusion (three lambs), or no infusion (two lambs). Rumen catheters were
      surgically implanted into lambs in the infusion groups. The amount of VFA
      infused, beginning at 2 wk of age, increased weekly in equal increments of 12.5%
      of the estimated net energy requirement until, at 6 wk of age, lambs received 50%
      of their estimated net energy requirement from the infused VFA. All lambs
      consumed milk replacer for ad libitum intake and had free access to water. The
      lambs that were infused with VFA tended to have longer rumen papillae. There were
      no differences in width or number of papillae per square centimeter across
      treatments. Rumen epithelial cells isolated from lambs that were infused with VFA
      tended to oxidize less glucose and produce more acetoacetate than did cells from
      lambs that were infused with saline or from uninfused lambs. beta-Hydroxybutyrate
      production by isolated rumen epithelial cells and concentrations of blood
      glucose, acetoacetate, and beta-hydroxybutyrate were not different among the
      three treatments. Thus, infusion of physiological concentrations of VFA appears
      to stimulate some aspects of rumen metabolic development.

PMID- 9149969
TI  - Effects of quality, quantity, and timing of colostrum feeding and addition of a
      dried colostrum supplement on immunoglobulin G1 absorption in Holstein bull
      calves.
AB  - Three experiments were conducted to examine the effects of quality, quantity, and
      timing of colostrum feeding and the administration of a dried colostrum
      supplement on serum Ig in Holstein bull calves. In Experiment 1, calves were fed
      colostrum that had low concentrations of immunoglobulin (Ig; 23.9 mg of IgG1/ml)
      as follows: group 1-1 (n = 6), 2 L at birth and 2 L at 12 h; group 1-2 (n = 6), 4
      L at birth and 2 L at 12 h; and group 1-3 (n = 6), 2 L at birth, 2 L at 6 h, and
      2 L at 12 h. Doubling the volume of colostrum administered at birth did not
      result in higher serum Ig at 48 h, but additional colostrum at 6 h did increase
      serum Ig. In Experiment 2, calves received 2 L of colostrum that had low
      concentrations of Ig (25.7 mg of IgG1/ml) at birth and 2 L at 12 h. Calves in
      group 2-1 (n = 6) received colostrum only. Calves in groups 2-2 (n = 5) and 2-3
      (n = 5) were fed additional dried colostrum supplement (136 and 272 g,
      respectively) at each meal. Addition of the supplement reduced efficiency of IgG1
      absorption and did not result in higher serum Ig at 48 h. In Experiment 3, calves
      were fed as follows: group 3-1 (n = 6), 2 L of colostrum containing 32.9 mg of
      IgG1/ml (low Ig) at birth and 2 L at 12 h; group 3-2 (n = 6), 2 L of colostrum
      containing 60.1 mg of IgG1/ml (high Ig) at birth and 2 L at 12 h, and group 3-3
      (n = 5), 4 L of colostrum containing 60.1 mg of IgG1/ml at birth and 2 L at 12 h.
      Colostrum high in Ig resulted in higher serum Ig concentrations at 48 h; the
      concentrations were highest when 4 L of colostrum high in Ig were fed to calves
      at birth.

PMID- 9149970
TI  - Effect of dystocia on yield, fertility, and cow losses and an economic evaluation
      of dystocia scores for Holsteins.
AB  - Lactation records of US Holstein cows were analyzed with mixed models to
      determine the effect of dystocia on 305-d milk, fat, and protein yields, days
      open, number of services, and cow losses and to estimate the economic loss
      associated with dystocia. The data were 122,715 records of 71,618 cows from 1980
      to 1991. The single-trait animal model included herd-year-season, sex of calf,
      age of dam, and dystocia score as fixed effects and animal and permanent
      environment as random effects. The effect of dystocia was significant (P < 0.01)
      on all traits within and across parities. Over multiple parities, the differences
      between score 5 (extreme difficulty) versus score 1 (no problem) for milk yield,
      fat yield, protein yield, days open, number of services, and cow deaths were
      703.6 kg, 24.1 kg, 20.8 kg, 33 d, 0.2 services, and 4.1%, respectively. The
      losses associated with traits were priced and summed to determine the total
      economic loss associated with dystocia. In addition, calf mortality was
      considered to be a cost. Across parities, estimates of costs were $0.00, $50.45,
      $96.48, $159.82, and $379.61 for scores 1 to 5, respectively. Cost of dystocia
      was relatively higher on a per incidence basis than would be expected from the
      mean of the population. The total cost associated with dystocia (i. e., within
      parity sum of costs associated with dystocia scores weighted by the probability
      of occurrence) was $28.53 for an average heifer and about $10.00 for an average
      cow for other parities.

PMID- 9149971
TI  - Estimates of genetic parameters for a test day model with random regressions for
      yield traits of first lactation Holsteins.
AB  - A model that contains both fixed and random linear regressions is described for
      analyzing test day records of dairy cows. Estimation of the variances and
      covariances for this model was achieved by Bayesian methods utilizing the Gibbs
      sampler to generate samples from the marginal posterior distributions. A single
      trait model was applied to yields of milk, fat, and protein of first lactation
      Holsteins. Heritabilities of 305-d lactation yields were 0.32, 0.28, and 0.28 for
      milk, fat, and protein, respectively. Heritabilities of daily yields were greater
      than for 305-d yields and varied from 0.40 to 0.59 for milk yield, 0.34 to 0.68
      for fat yield, and 0.33 to 0.69 for protein yield. The highest heritabilities
      were within the first 10 d of lactation for all traits. Genetic correlations
      between daily yields were higher as the interval between tests decreased, and
      correlations of daily yields with 305-d yields were greatest during midlactation.

PMID- 9149972
TI  - Relationship of yield during early lactation and days open during current
      lactation with 305-day yield.
AB  - To measure and to partition the effect of pregnancy on yield, the relationships
      among milk, fat, and protein yields during early lactation, current days open,
      and 305-d yields were investigated using sample day records of 247,310 Holstein
      cows. The model included fixed effects of calving herd-year-season, calving age,
      and days open; the continuous variable of early cumulative yield to 80, 100, 120,
      or 140 d; and a random residual effect. As days open during first lactation
      increased from 30 to 100 d, 305-d milk yield increased by 876 kg; as days open
      increased from 100 to 200 d, milk yield increased by only 172 kg. The impact of
      current days open was greater on second lactation than on first; the difference
      in 305-d milk yield between cows open 40 and 290 d was 1199 kg for first
      lactation and 1613 kg for second lactation. If early yield to 120 d was included
      in the model, the corresponding difference was reduced to 860 kg for first
      lactation and 1001 kg for second lactation. Inclusion of early yield in the model
      reduced regression coefficients for days open during first lactation by 22% for
      80-d yield, 24% for 100-d yield, 27% for 120-d yield, and 30% for 140-d yield and
      by 31, 35, 38, and 41%, respectively, for second lactation. Statistical models to
      derive adjustment factors should account for early lactation yield so that those
      factors can remove effects of pregnancy but not correlations between yield and
      fertility caused by early yield.

PMID- 9149973
TI  - Implementing a quality assurance program using a risk assessment tool on dairy
      operations.
AB  - Concerns and perceptions about antibiotic residues in milk prompted the dairy
      industry to develop a voluntary program to support rational antibiotic use on
      dairy farms. One deficiency of this program is the inability of producers to
      identify easily the weaknesses in antibiotic management in order to develop
      control plans. To overcome this deficiency, an educational approach was designed.
      The program centered on an on-farm risk assessment tool used by the producer and
      an industry educator to determine the current risk for residue violation. The
      risk assessment tool was tested by 25 field personnel working with northeastern
      milk receivers and 250 producers in seven states. The participants in the study
      identified a lack of adequate treatment records as being the highest risk factor
      for antibiotic residues, followed by deficiencies in understanding how to use
      antibiotics and poor relationships between veterinarians and their clients. When
      field representatives utilized the risk assessment tool, for most producers, risk
      of antibiotic residue decreased by approximately 19%. In particular, more farms
      kept written records or more complete records. Finally, producers with reported
      histories of antibiotic residues were less likely to implement management changes
      to reduce the risk of antibiotic residue.

PMID- 9149974
TI  - Activity of selected antimicrobial agents against strains of Staphylococcus
      aureus isolated from bovine intramammary infections that produce beta-lactamase.
AB  - The activity of selected antimicrobial agents was determined against strains of
      Staphylococcus aureus that were isolated from bovine intramammary infections and
      that were positive or negative for beta-lactamase. A total of 107 S. aureus
      strains (70 that were positive for beta-lactamase and 37 that were negative for
      beta-lactamase) were used in the study. Production of beta-lactamase was
      determined using a chromogenic cephalosporin disk method. Minimum inhibitory
      concentrations (MIC) for each test strain were determined using a commercially
      available microdilution panel. The following compounds were tested: penicillin,
      ampicillin, oxacillin, cephapirin, ceftiofur, penicillin plus novobiocin,
      erythromycin, and pirlimycin. Of the five beta-lactam compounds tested,
      penicillin and ampicillin were most affected by beta-lactamase activity, but
      oxacillin, cephapirin, and ceftiofur were not affected. Penicillin plus
      novobiocin also demonstrated excellent activity against strains of S. aureus that
      were both positive and negative for beta-lactamase. Erythromycin and pirlimycin
      demonstrated good activity against the S. aureus strains that were negative for
      beta-lactamase; 90% of the isolates had an MIC of < or = 0.5 microgram/ml
      (MIC90). The MIC90 for erythromycin and pirlimycin for strains that were positive
      for beta-lactamase was > 64.0 micrograms/ml. However, 8 strains, in addition to
      producing beta-lactamase, were also resistant to macrolides and lincosaminides.
      Recalculation of the MIC90 without these 8 strains yielded equivalent values for
      both erythromycin and pirlimycin with strains that were positive or negative for
      beta-lactamase (MIC90 < or = 0.5 microgram/ml).

PMID- 9149975
TI  - A non-invasive method for studying in vivo carpal kinematics.
AB  - Seven uninjured and three injured patients were studied using midsagittal
      computed tomographic (CT) images at 10 degrees increments from full extension to
      full flexion. Each injured patient had a confirmed scapholunate ligament tear and
      normal radiographs. CT bony contours were digitized, and incremental motion
      determined using a specifically designed automated contour-matching algorithm. We
      expressed wrist motion as a ratio of lunocapitate (midcarpal) motion, and
      radiolunate (radiocarpal) motion. In normal wrists, motion occurred equally at
      the midcarpal and radiocarpal joints. In wrists with scapholunate ligament
      disruption, lunocapitate motion increased significantly throughout the arc of
      motion.

PMID- 9149976
TI  - Experience with scaphoid grafting.
AB  - Over a period of 24 years, the author has used five different methods of bone
      grafting for ununited scaphoid fractures. The clinical and radiological results
      have been reviewed, with a minimum follow-up of 1 year. Radiologically the best
      results (78% definite union) were obtained with a "wedge" graft and Herbert
      screw, while the worst results followed the original Russe operation. The
      clinical result often did not coincide with the radiological outcome. All methods
      led to a decrease in pain in most cases, but little or no pain was achieved most
      often by the modified Russe graft. With proximal pole fractures, bony union was
      only achieved in 54% but the symptoms were always lessened.

PMID- 9149978
TI  - Congenital fusion of the scaphoid, trapezium, trapezoid and capitate.
AB  - We describe an unusual case of carpal coalition in an otherwise asymptomatic 28
      year-old man. The combination of scaphoid, trapezium, trapezoid and capitate
      fusion detailed in this article has not, to the best of our knowledge, been
      previously recorded.

PMID- 9149977
TI  - Registration bone scan in the evaluation of wrist pain.
AB  - We assessed the value of bone scintigraphy combined with X-ray registration for
      the diagnosis and management of wrist pain in 65 patients. Studies were reported
      independently by two observers before and after registration. Registration
      improved localization of scan abnormalities in 53% (observer 1) and 61% (observer
      2). In these patients, the bone scan contributed to the diagnosis independently
      of the X-ray in 37% and the management was altered in 31%. The value of the bone
      scan in the early diagnosis and management of wrist pain is increased when it is
      registered with X-rays.

PMID- 9149979
TI  - Bilateral transscapholunate dislocations.
AB  - Bilateral transscapholunate dislocations were treated with immediate open
      reduction and internal fixation. Eighteen months after injury the patient was
      asymptomatic.

PMID- 9149980
TI  - Scapholunate dissociation in the skeletally immature carpus.
AB  - Scapholunate dissociation is well documented as a condition occurring in adult
      patients. We report it in a 14-year-old female patient. Persistent wrist pain 9
      months after a well healed fracture of the distal radius triggered further
      investigation. Dynamic clinical and radiological studies demonstrated the
      instability.

PMID- 9149981
TI  - Nonunion of a distal radial fracture in a healthy child.
AB  - Nonunion of distal radial fractures in children are rare. We report a case of a
      closed distal radial fracture in a healthy child, which developed a nonunion
      following closed reduction and plaster immobilization.

PMID- 9149982
TI  - Algodystrophy is an early complication of Colles' fracture. What are the
      implications?
AB  - One hundred patients who had sustained a Colles' fracture were observed for
      features of algodystrophy at 1, 5, 9 and 12 weeks following injury. The diagnosis
      of algodystrophy was possible as soon as 1 week after fracture. Early diagnosis
      has important clinical implications: the aetiological factors may become apparent
      and different treatment modalities be identified; furthermore, early treatment
      can be started, limiting the morbidity of the condition. It is proposed that
      patients with features of algodystrophy require physiotherapy after a Colles'
      fracture. Those without features may not.

PMID- 9149984
TI  - Scaphotrapeziotrapezoid osteoarthritis after scaphotrapezial ligament injury.

PMID- 9149983
TI  - Anatomical and biomechanical studies of the pathogenesis of trapeziometacarpal
      degenerative arthritis.
AB  - An anatomical and biomechanical study of the stabilizing ligaments of the thumb
      trapeziometacarpal joint was conducted on 32 hand specimens. Five main
      ligamentous structures could be identified. The mechanical properties (in
      particular, strength) of the five ligaments using a strain-rate failure test were
      determined and evaluated quantitatively. The maximum tensile strength of each
      ligament was correlated with the condition of the trapeziometacarpal articular
      cartilage. In studying the anterior oblique ligament, maximum strength decreased
      from Grade 0 to Grade 1 by 51%. With the first intermetacarpal ligament, the drop
      from Grade 1 to Grade 2 was 53%. With the posterior oblique ligament, the
      decrease was closely related to the grade of the deterioration of the
      trapeziometacarpal articular surface. These three ligaments also significantly
      decreased in strength with age. Our results may suggest that the anterior oblique
      ligament, intermetacarpal ligament and posterior oblique ligament play a large
      role in stabilizing the trapeziometacarpal joint and that the decrease in their
      strength is related to the pathogenesis of trapeziometacarpal osteoarthritis.

PMID- 9149986
TI  - Skin replacement in Dupuytren's disease.
AB  - We have reviewed 90 rays in 67 patients who had undergone radical digital
      dermofasciectomy. Follow-up was from 24 to 100 months. Problems with skin grafts,
      moving two-point discrimination and active range of joint movement were noted.
      The recurrence rate in this series was 8%, a very much better figure for disease
      control than has been reported for standard approaches for Dupuytren's disease.
      Radical digital dermofasciectomy is strongly recommended for all cases of
      recurrent Dupuytren's disease requiring reoperation and as a primary procedure
      when there is significant skin involvement.

PMID- 9149985
TI  - Day care surgery for advanced Dupuytren's contracture.
AB  - Seventy-six consecutive patients suffering from advanced Dupuytren's contracture
      were analysed in order to evaluate the safety of day care surgery. The
      complication rates for haematoma, necrosis, infection and reflex sympathetic
      dystrophy were acceptable, but we found an unacceptably high percentage of nerve
      lesions. Day care treatment was achieved in all but seven cases. We concluded
      that advanced Dupuytren's contracture can be treated by day care surgery but the
      operations should be performed by surgeons who are skilled in hand surgery, and
      individual selection of patients with recurrence seems advisable.

PMID- 9149987
TI  - A historical record of traumatic rupture of Dupuytren's contracture.
AB  - Traumatic rupture of Dupuytren's contracture is rare. It has been reported only
      twice in recent times and only on four previous occasions over the last
      millenium. These cases are reported and the forces involved in rupturing
      Dupuytren's contracture are discussed.

PMID- 9149988
TI  - The consequences of punching glass.
AB  - We carried out a retrospective and prospective study of 67 patients who had
      sustained hand injuries from punching glass over a period of 33 months. All had
      consumed alcohol and had argued with a partner. The mean age was 25 years, 90%
      were male and 56% were unemployed. Seventy per cent of injuries occurred between
      23.00 and 04.00 hours. Total damage included division of 149 tendons, 33 nerves
      and nine arteries. Fifty-two per cent of patients required admission for more
      than 1 day. The mean number of follow-up visits was 3.6 and the majority needed
      hand therapy and occupational therapy services. Cost per injury was estimated as
      1,120 pounds. Such injuries cause major disability in an already disadvantaged
      section of society. The challenge is to educate the susceptible patient group.

PMID- 9149989
TI  - The distally based ulnar artery island flap in hand reconstruction.
AB  - The distally based ulnar artery island flap is a highly versatile flap for hand
      reconstruction. It fulfils all the necessary criteria required for a flap to the
      hand providing thin pliable hairless skin. It can be used as a composite flap
      including tendon and bone and provides an ideal tunnel for tendons to glide in.
      It can be used as a fasciocutaneous flap or as a fascial flap and can easily be
      rotated to the dorsum of the hand by opening Guyon's canal. The palm or dorsum of
      the hand and even the fingertips can be reached easily. A superficial venous
      anastomosis should be made if marked venous congestion is noted intraoperatively.
      Six cases utilizing a distally based ulnar island flap in hand reconstruction are
      presented.

PMID- 9149990
TI  - Extending the use of the palmar advancement flap with V-Y closure.

PMID- 9149991
TI  - Improving the results of ganglion aspiration by the use of hyaluronidase.
AB  - We present the results of a prospective randomized trial comparing the treatment
      of ganglia by aspiration under local anaesthetic and either instillation of
      steroid alone or with the prior use of hyaluronidase. Thirty-five patients were
      treated in each group and followed up for 2 years. The cure rate with the
      combined use of hyaluronidase and methylprednisolone was 89%, compared to 57%
      when treated by aspiration and instillation of methylprednisolone alone.

PMID- 9149992
TI  - Complications following mucous cyst excision.
AB  - Eighty-six mucous cysts in 79 patients were surgically excised. Follow-up was
      carried out at an average of 2.6 years. Fifteen digits (17%) had a residual loss
      of extension of 5 to 20 degrees at the IP or DIP joints. One patient developed a
      superficial infection and two developed a DIP pyarthrosis, which eventually
      required DIP arthrodesis. Nail deformities were present in 25 of 86 digits
      preoperatively (29%), 15 of which resolved after surgery (60%). Four of 61 digits
      developed a nail deformity which was not present preoperatively (7%). Three of 86
      digits (3%) developed recurrence. Other complications included persistent
      swelling, pain, numbness, stiffness, and radial or ulnar deviation at the DIP
      joint. We recommend that patients be informed preoperatively of the potential
      risks of decreased range of motion, persistent swelling and pain, infection,
      recurrence, and persistent or postoperatively acquired nail deformity.

PMID- 9149993
TI  - The distribution of fibrous flexor sheath ganglions.
AB  - The distribution of fibrous flexor sheath ganglions was studied in 57 patients.
      They were found to be more common in the third decade and in the middle finger.
      Both hands were equally affected. There was no clear relationship to occupation
      or repeated trauma. The striking finding in our study was the male predominance.

PMID- 9149994
TI  - Subungual glomus tumours: a different approach to diagnosis and treatment.
AB  - Nine cases of subungual glomus tumour in which a transillumination test was used
      for diagnosis and a different operative technique was used to prevent
      postoperative nail deformity are described. The transillumination test is a new
      method for identifying a glomus tumour. With our surgical technique it is simple
      to approach a glomus tumour under the proximal nail bed and it produces a minimal
      defect.

PMID- 9149995
TI  - The treatment of enchondromas in the hand by endoscopic curettage without bone
      grafting.
AB  - Nine patients with enchondromas in the hand were treated by endoscopic curettage
      of the tumour without bone grafting. The procedure was performed on an out
      patient basis using axillary block anaesthesia. New bone formation and
      remodelling of the lesions were observed in all patients. There were no
      postoperative fractures, infections, recurrences or other complications.
      Functional recovery was rapid. We conclude that endoscopic curettage without bone
      grafting is an effective treatment of enchondroma in the hand.

PMID- 9149996
TI  - Enchondroma of the scaphoid.
AB  - Enchondroma is a common benign cartilaginous tumour which arises from the
      medullary cavity, most commonly in the phalanges of the hands and feet.
      Enchondroma involving the carpal bones, however, is rare; only three cases of
      scaphoid enchondromata and one patient with multiple carpal enchondromata have
      been reported in the English literature. We report the diagnosis and treatment of
      a case of scaphoid enchondroma presenting as chronic wrist pain after relatively
      trivial injury.

PMID- 9149997
TI  - Chondrosarcoma of the hand arising in a young patient with multiple hereditary
      exostoses.

PMID- 9149998
TI  - Transient bradycardia in a mouse model for the oromandibulofacial limb
      hypogenesis syndrome following chorionic villus sampling.
AB  - Amniotic sac puncture carried out on day 13 mouse embryos induces a high
      incidence of craniofacial and limb abnormalities that resemble the anomalies seen
      in the oromandibulofacial limb hypogenesis syndrome occasionally encountered
      following chorionic villus sampling carried out during early human pregnancy. It
      has been hypothesized that this syndrome probably has a vascular basis, possibly
      due to hypotension and hypoperfusion of tissues secondary to placental trauma,
      though no detailed aetiology has so far been described. We have determined
      embryonic heart rates in control embryos, in embryos at intervals following
      anaesthesia, and following amniotic sac puncture. An increased duration of
      bradycardia is seen following this procedure which is not observed in anaesthetic
      only controls and in embryos in the contralateral (non-operated) uterine horns.
      We discuss why the incidence of oromandibulofacial limb hypogenesis syndrome is
      low following chorionic villus sampling, and propose a possible aetiology for the
      limb abnormalities seen in this condition.

PMID- 9149999
TI  - Classification of limb anomalies in oral-facial-digital syndromes.
AB  - A classification of limb anomalies in oral-facial-digital (OFD) syndromes is
      offered to help differentiate between the various types of OFD syndromes. A
      clinical case is presented with clinical features consistent with both OFD
      syndrome type I (Papillon Leage-Psaume syndrome) and type VI (Varadi syndrome).
      The final diagnosis as a new mutation of type I syndrome was established after
      reviewing the radiological findings in the hands.

PMID- 9150000
TI  - Unilateral hypertrophy of the upper extremity due to aberrant muscles.
AB  - We present a case of congenital unilateral hypertrophy of an upper extremity due
      to aberrant muscles. Reviewing the previous Japanese reports, we discuss the
      clinical features and the pathogenetic factors of this rare anomaly.

PMID- 9150001
TI  - Functional motor innervation of brachial plexus roots. An intraoperative
      electrophysiological study.
AB  - The electrophysiological properties of the normal brachial plexus and functional
      motor innervation were examined during the operation of transfer of contralateral
      C7 transfer from the healthy side. Different roots of the brachial plexus were
      stimulated and maximum amplitudes were recorded. The results showed that
      functional motor innervation of brachial plexus roots were: C5 mainly forms the
      axillary nerve to innervate the deltoid muscle; C6 mainly forms the
      musculocutaneous nerve to innervate biceps; C7 mainly forms the radial nerve to
      innervate triceps; C8 mainly forms the median nerve to innervate flexor digitorum
      superficialis and profundus; and T1 mainly forms the ulnar nerve to innervate the
      intrinsic muscles of the hand.

PMID- 9150002
TI  - Transposition of the bicipital tuberosity for treatment of fixed supination
      contracture in obstetric brachial plexus lesions.
AB  - In nine patients with obstetric brachial plexus lesions (Klumpke type), an
      impingement of the bicipital tuberosity on the ulna was the main cause for the
      forearm and hand to be fixed in supination. A surgical technique using
      reinsertion of the biceps tendon on the bicipital tuberosity is described in
      detail. It has substantially improved all patients. After a mean follow-up of
      29.4 months the hand was in a more functional position than preoperatively in all
      patients. In seven cases pronation could be increased by contraction of the
      biceps muscle. By relaxing the biceps muscle and by contraction of the supinator
      muscle a limited active supination was possible in six cases.

PMID- 9150003
TI  - Closure of fasciotomy wounds. A technical modification.
AB  - The closure of fasciotomy wounds creates problems for patient and surgeon alike.
      Split thickness skin grafting results in unsightly and insensate wounds and often
      requires general anaesthesia and prolonged inpatient care. We describe an
      improvement of a previously reported technique which is as effective as
      proprietary medical devices currently available. The technique may also be
      applied to the delayed primary closure of traumatic wounds.

PMID- 9150004
TI  - Grip and pinch strength variations in different types of workers.
AB  - We measured grip and pinch strengths in non-manual, light manual and heavy manual
      workers using a Jamar dynamometer and a pinch measuring device. Heavy manual
      workers had the strongest grips with the least difference between sides. Office
      workers had the weakest grips and the greatest difference between sides. Light
      manual workers were between these two groups. Consequently, the occupation of the
      patient must be taken into account when using grip and pinch strength
      measurements to assess the need for rehabilitation and in medicolegal reports.

PMID- 9150005
TI  - Passive axial rotation of the metacarpophalangeal joint.
AB  - We measured passive axial rotation at the metacarpophalangeal (MCP) joints of the
      index, long, ring and small fingers of both hands in 100 healthy subjects using a
      magnetic position and orientation system called an Isotrak. Large degrees of
      passive rotation were found, with the ring and small finger MCP joints displaying
      significantly greater ranges of supination than the other two joints. Supination
      ranges were also found to be significantly greater than the pronation values in
      each joint. These results support present anatomical understanding that, during
      prehensile activities, axial rotation of the MCP joints occurs to allow the hand
      to adapt to an object being held.

PMID- 9150006
TI  - Reconstruction of a metacarpophalangeal pulley in the thumb with a free extensor
      retinaculum graft.

PMID- 9150007
TI  - Variations of the flexor digitorum superficialis tendon of the little finger.
AB  - Seventy cadaveric hands were dissected to study variations of the flexor
      digitorum superficialis tendon (FDS) to the little finger. Anatomical variations
      were present in 13% of hands and 10% of the hands showed an anatomical variation
      that would preclude independent FDS function in the little finger. The distance
      of the decussation from the metacarpophalangeal joint was measured. A ratio of
      this distance to proximal phalangeal length was calculated. The ratio indicated
      that decussation position was independent of phalangeal size.

PMID- 9150008
TI  - Complete avulsion of the extensor apparatus of the little finger.

PMID- 9150009
TI  - Results of dynamic splintage following extensor tendon repair.
AB  - We report a prospective study of dynamic splintage following extensor tendon
      repair. Eighty-four patients with 101 extensor tendon injuries were studied.
      Using Dargan's evaluation system, there were 97% excellent results for the thumb
      and 93% excellent and good results for the fingers. The average total active
      motions were 107 degrees for thumbs and 245 degrees for fingers. Over 80% of
      patients regained good power grip. Patients with associated digital fractures or
      with ragged lacerations had poorer results. Overall, we found that dynamic
      splintage was a satisfactory method after extensor repair.

PMID- 9150010
TI  - MRI of the proximal interphalangeal joints.

PMID- 9150011
TI  - Compartment syndromes and epidural analgesia.

PMID- 9150012
TI  - Compartment syndrome associated with bupivacaine and fentanyl epidural analgesia
      in pediatric orthopaedics.
AB  - Two patients had a compartment syndrome after surgery at a remote site performed
      under a continuous lumbar infusion of a mixture of narcotic (fentanyl) and local
      anesthetic (bupivacaine 0.1%). Each patient had inadvertent excessive pressure
      applied to the limb distally and had no perception of pain in the presence of
      this analgesic combination. After the relief of this pressure from a sling or
      traction apparatus, each child had signs of a compartment syndrome, and this
      sensation of pathologic pain was not masked by the epidural infusion. A
      discussion of the literature questions the benefits of bupivacaine local
      anesthetic as a routine addition to epidural analgesia for orthopaedic surgery.

PMID- 9150013
TI  - Does sympathetic blockade prevent the physiologic changes associated with
      tourniquet use in children?
AB  - This study investigated a means of controlling the altered physiologic effects
      that occur when tourniquet inflation time is > or = 50 min during orthopaedic
      surgery in children. Forty patients were assigned randomly, 20 in each group.
      Both groups received inhalational anesthesia for induction. The control group had
      nitrous/narcotic with inhalation anesthesia for maintenance. The other group
      received a sympathetic blockade with 0.5% epidural bupivacaine, which was
      confirmed with the use of thermography technique and supplemented with 0.5-1%
      isoflurane. Duration of surgery and length of tourniquet inflation time were
      equal in the two groups. There was a significant difference in physiologic
      changes related to the tourniquet inflation time. The group with sympathetic
      blockade had only minor changes in blood pressure, pulse rate, and temperature
      compared with the control group.

PMID- 9150014
TI  - Humerus shaft fractures in young children: accident or abuse?
AB  - We performed a retrospective review of 34 humerus shaft fractures (HSFs) in
      children younger than 3 years to determine the frequency of child abuse in young
      children with this injury. Data were obtained from hospital records (including
      previous and subsequent emergency, clinic, and inpatient notes), radiographs, and
      county childprotective services. Cases were reviewed independently by four
      physicians and were classified as probable abuse, probable not abuse, and
      indeterminate. Only 18% were classified as probable abuse. The history and
      findings other than the fracture itself were critical in establishing cause.
      Neither age nor fracture pattern is pathognomonic of abuse, but suspicion should
      remain high. A detailed history, complete physical examination, and appropriate
      radiographic investigation are required in every case either to make the
      diagnosis of abuse or to avoid the trauma of a false accusation.

PMID- 9150015
TI  - Brachialis muscle entrapment in displaced supracondylar humerus fractures: a
      technique of closed reduction and report of initial results.
AB  - A retrospective review was conducted of 152 extension-type supracondylar humerus
      fractures in 151 children. Ninety-two (61%) of 152 of these fractures were
      displaced (Gartland type III). Initial irreducibility was present in 20 of the 92
      displaced fractures. Brachialis muscle interposition was diagnosed by physical
      examination or intraoperative findings in 18 (90%) of the 20 initially
      irreducible fractures. Sixteen of the fractures with brachialis muscle
      interposition underwent an attempt at freeing the impaled proximal fragment by
      the described "milking maneuver." The maneuver was successful in 15 of the 16
      patients and was followed by closed reduction and percutaneous pinning. Three of
      the remaining four cases required open reduction and pinning. We identify the
      incidence of initial irreducibility in displaced supracondylar humerus fractures,
      describe clinical findings suggestive of brachialis entrapment, and demonstrate
      the milking maneuver to be a valuable technique in the treatment of displaced
      supracondylar fractures with brachialis interposition.

PMID- 9150016
TI  - Management of pulseless pink hand in pediatric supracondylar fractures of
      humerus.
AB  - Thirteen (3.2%) of 410 patients seen in British Columbia's Children's Hospital in
      Vancouver from January 1984 to September 1992 with supracondylar fractures did so
      with an absence of a radial pulse in an otherwise well perfused hand. A
      combination of segmental pressure monitoring, color-flow duplex scanning, and
      magnetic resonance angiography (MRA) appears to be a valid, noninvasive, and safe
      technique in evaluating patency of the brachial artery and collateral circulation
      across the elbow. Based on this study, early revascularization of a pulseless
      otherwise well-perfused hand in children with type 3 supracondylar fractures,
      although technically feasible and safe, has a high rate of asymptomatic
      reocclusion and residual stenoses of the brachial artery. Therefore a period of
      close observation with frequent neurovascular checks should be completed before
      more invasive correction of this problem is contemplated.

PMID- 9150017
TI  - Osteochondral lesions in the radiocapitellar joint in the skeletally immature:
      radiographic, MRI, and arthroscopic findings in 13 consecutive cases.
AB  - Radiography, magnetic resonance imaging (MRI), and arthroscopy were performed in
      13 consecutive cases of osteochondral lesions of the radiocapitellar joint in 12
      patients aged 11-16 years. Nine patients had a high activity level, and two
      patients had a significant trauma before the onset of symptoms. Symptoms were
      limited range of motion, pain, and catchings or lockings. Clinical findings were
      decreased range of motion and lateral elbow tenderness. Radiography revealed
      loose body, flattening of the humeral capitellum, or subchondral cysts (or a
      combination of these) in all cases but three. There was a good correlation
      between MRI and arthroscopic examination. Nine lesions were located in the
      humeral capitellum, one lesion in the radial head, and in three cases, lesions
      were found in both sites. Loose-body removal, shaving, or subchondral drilling
      (or a combination of these) was performed in 11 cases. All surgically treated
      patients improved in the short run. Awareness of the typical clinical and
      radiologic picture will allow identification of the cases suitable for
      arthroscopy and surgical treatment. In these cases, MRI can be omitted.

PMID- 9150018
TI  - Fractures of the capitellum in adolescents.
AB  - Fractures of the capitellum are rare in children. The treatment of these injuries
      has been controversial. At a major pediatric trauma center, seven capitellar
      fractures were seen in children between 1988 and 1994. The average age of the
      children was 14.7 years (range, 11-17). Six of these fractures were type I
      injuries, with large anterosuperior fragments that required operative reduction
      and internal fixation in five cases. Internal fixation methods used were K wires
      in three patients, Herbert screws in one patient, and cannulated screws in one
      patient. The remaining type I fracture was treated with a closed reduction. The
      seventh fracture was a type II fracture, treated nonoperatively. Five children
      did well with their respective treatments, but one required reoperation to remove
      an exostosis block to flexion. Accurate open reduction and internal fixation for
      the displaced capitellar fracture in children is an effective treatment to
      restore normal elbow function.

PMID- 9150019
TI  - Surgical treatment of displaced olecranon fractures in children.
AB  - Thirty-five children who had fractures of the olecranon were reviewed. Age at the
      time of injury ranged from 0 years 2 months to 15 years 4 months. Fractures were
      retrospectively classified as type I or II according to the amount of
      displacement apparent on the initial radiographs. Type I fractures were those
      with < 3 mm of displacement, and type II were those with displacement of > or = 3
      mm. Type I fractures (n = 23) were treated with closed methods, and splint or
      cast immobilization was maintained for an average of 3 weeks. All 23 type I
      fractures had satisfactory results on follow-up. Type II fractures (n = 12) were
      treated with open reduction and internal fixation. Greater intraarticular
      displacement was often seen intraoperatively than had been appreciated
      radiographically. Ten of 12 patients with type II fractures were available for
      follow-up; all had satisfactory results. Restoration of the articular surface in
      children with olecranon fractures optimizes joint function and growth potential.
      The amount of fracture may be more than is apparent on plain radiographs.

PMID- 9150020
TI  - Displaced radial neck fractures in children treated by closed intramedullary
      pinning (Metaizeau technique).
AB  - We report the retrospective results of 17 displaced radial neck fractures
      (O'Brien type II-III) in children aged between 6 and 16 years treated with closed
      intramedullary pinning according to the Metaizeau technique, from 1988 to 1992 in
      our Pediatric Orthopaedic Service at the Ramon y Cajal Hospital. The average
      follow-up was 4.1 years. Excellent results were observed in all cases except one
      (94%). Overgrowth of the radial head was present in three cases without
      functional impairment. We recommend this closed method of treatment because it is
      simple, easy to perform, and obtains exciting results with few complications.

PMID- 9150021
TI  - Factors affecting fracture position at cast removal after pediatric forearm
      fracture.
AB  - The outcome of a pediatric forearm fracture is related to the angulation of that
      fracture at the time of union. We discuss the factors affecting the position of
      the fracture at union. Three hundred forty-six children with 369 reductions of
      forearm fractures were reviewed retrospectively. Quality of reduction at the time
      of operation and loss of reduction during the period of cast immobilization were
      assessed using axis deviation. Loss of reduction had a greater influence on the
      final position of the fracture at union than did the position of the fracture at
      initial reduction. To ensure a satisfactory outcome, all pediatric forearm
      fractures should be monitored with radiologic review and remanipulation if their
      axis deviation is > 5 in younger patients or > 3 in patients with fractures close
      to or after growth-plate closure. Right forearm fractures in boys were identified
      as a subgroup at greater risk for redisplacement.

PMID- 9150022
TI  - Long-term outcome of sacroiliac disruptions in children.
AB  - We retrospectively evaluated the outcome of sacroiliac-joint disruption in 18
      children, ranging in age from 2 to 16 years. Ten patients were treated with
      bedrest; eight were treated surgically. Follow-up was performed at an average of
      14 years (range, 8-23); three patients had daily back pain, and six had
      occasional back pain. Six patients had limited lumbosacral motion, but only two
      were symptomatic. The sacroiliac joint was fused in nine patients and irregular
      in four. Fracture reduction had been incomplete in nine patients, of whom five
      had a vertical shear injury. All developed complete or incomplete fusion of the
      sacroiliac joint, but we could not find a clear relationship between the often
      impressive radiographic changes and symptoms. Nine patients had a leg-length
      discrepancy of > 1 cm; three patients had pelvic asymmetry. Disabling long-term
      symptoms persisted from incomplete neurologic recovery in six patients.

PMID- 9150023
TI  - External fixation of pediatric femur fractures.
AB  - One-hundred and thirty-two children with 139 femur fractures were treated with
      external fixation from 1984 to 1993. Average age at presentation was 8.97 years.
      All fractures were followed until union, with an average time of external
      fixation of 11.4 weeks. There were no nonunions. Of 18 patients with definitive
      radiographic measurements at 2-year follow-up, 15 patients developed overgrowth
      (average, 8.7 mm) and three demonstrated shortening (average, 7.7 mm). No patient
      required treatment for residual leg-length discrepancy. Although pin-tract
      inflammation was common, pin-tract infection requiring intravenous antibiotics
      occurred in only six patients (4.5%). No patient developed osteomyelitis. Two
      fractures (1.4%) were not healed at the time of elective fixator removal,
      necessitating additional time in the fixator. There were two refractures (1.4%)
      and one fracture through a healing pin tract after fixator removal (0.7%).

PMID- 9150024
TI  - Isolated fractures of the tibia with intact fibula in children: a review of 95
      patients.
AB  - Isolated tibial fractures with an intact fibula are the most common tibial
      fracture pattern in children. When displaced, this fracture can be difficult to
      reduce and retain in the position because of the splinting of the intact fibula.
      A 4-year review of 95 children with fracture of the tibia with an intact fibula
      was performed at the Children's Hospital of Eastern Ontario. Eighty-one percent
      of the fractures were caused by an indirect rotational twisting force. Seventy
      three percent of fractures were localized at the distal third of the tibial
      shaft. Varus angulation deformity occurred most commonly when the fracture line
      started distally on the anteromedial side of the tibia and progressed in an
      oblique or spiral manner to the proximal posterolateral aspect of the tibia. This
      was postulated to be caused by the posterior flexor muscle forces being more
      concentrated medially, whereas laterally, the intact fibula acts like a splint,
      thus producing a bending moment resulting in varus angulation. Close follow-up
      and monitoring of the isolated tibial fractures with weekly radiographs for the
      first 3 weeks is recommended.

PMID- 9150025
TI  - Intramalleolar triplane fractures of the distal tibial epiphysis.
AB  - The intramalleolar triplane fracture of the distal tibial epiphysis is a
      relatively rare injury in children. We studied five children with intramalleolar
      triplane fractures. Four of the five children were competitive athletes. Each
      child underwent computerized tomography with three-dimensional reconstruction.
      Delineation of the intramalleolar fracture pattern with computerized tomography
      with three-dimensional reconstruction demonstrated three distinct types of
      intramalleolar triplane fractures: I. intraarticular and within the weight
      bearing zone, II. intraarticular and outside the weight-bearing zone, and III.
      extraarticular. Computerized tomography with three-dimensional reconstruction
      delineated the fracture pattern and allowed selection of the optimal treatment
      method. A classification scheme of the three types of intramalleolar triplane
      fracture is proposed.

PMID- 9150026
TI  - The use of helical computed tomographic scan to assess bony physeal bridges.
AB  - Coronal and sagittal reformatted images of the physis obtained with the helical
      computed tomography (CT) scanner were studied in five children. This technique
      allows tomographic slices at 1.0-mm thickness and can be performed in
      approximately 20 s. The distal femora were studied in two children, the distal
      tibia in two children, and the distal radius in one child. In three children,
      after physeal mapping, bar resections were performed. In all cases, the location
      and size of the bar was accurately predicted by the map constructed from the
      helical CT scan. We recommend the helical CT scan to prepare physeal maps to
      determine the extent and location of physeal bony bars because of excellent bony
      detail, radiation doses one half to one quarter those of conventional tomography,
      and the rapidity of scanning, which bypasses the need for sedation.

PMID- 9150027
TI  - Extremity lawn-mower injuries in children: report by the Research Committee of
      the Pediatric Orthopaedic Society of North America.
AB  - In a multicenter study of pediatric lawn-mower injuries (push or riding gas
      powered machines), we reviewed 144 children at an average age of injury of 7.0
      years; 77% were boys. Most injuries (92 of 104) occurred in the afternoon. The
      child was the machine operator in 36 cases, a bystander in 84, and a passenger in
      21. The average hospital stay was 13.3 days with 2.6 surgeries per child.
      Amputations occurred in 67 children; 63 were unilateral and four bilateral; the
      most common level was the toes (63%). Blood transfusions were given to 35
      children. Children injured by riding lawn mowers, when compared with those by
      push lawn mowers, were younger (5.4 vs. 11.0 years), less frequently the operator
      (15 vs. 60%), had longer hospitalizations (15.0 vs. 8.9 days), and required more
      surgeries (3.0 vs. 1.6) and blood transfusions (41 vs. 3%). Children with free
      flaps needed more transfusions (78 vs. 26%), and transfused children were younger
      (4.6 vs. 8.1 years), more likely to be bystanders (91 vs. 63%), required more
      surgeries (4.1 vs. 2.0), and were hospitalized longer (21.6 vs. 9.7 days). Soft
      tissue infections occurred in eight of 118 and osteomyelitis occurred in six of
      117 children. At an average follow-up of 1.9 years, there were 43 satisfactory
      and 84 unsatisfactory results. When excluding those children with amputations of
      digits, there were 42 satisfactory and 47 unsatisfactory results. If children
      younger than 14 years had not been permitted around lawn mowers, approximately
      85% of the injuries in this report would have been prevented. Further public
      dissemination of the following information is needed: (a) children younger than
      14 years should not operate lawn mowers, (b) children younger than 14 years
      should not be in the yard while the lawn is being mowed, and (c) no passengers,
      regardless of age, should be allowed on riding mowers.

PMID- 9150028
TI  - Ankle-foot orthoses for preambulatory children with spastic diplegia.
AB  - We evaluated the effect of articulating and solid ankle-foot orthoses (AFOs) on
      the transitional movement of sit-to-stand for 15 children aged 2-5 years with
      spastic diplegia and dynamic equinus. Kinematic and kinetic data were collected
      for each child. The time to reach stable standing was determined by using a force
      plate. Seven children were comparable to age-matched normals while barefoot and
      were slowed by the use of AFOs. Eight patients were more than 1 standard
      deviation slower than normals while barefoot. All were significantly (p < 0.003)
      improved by the use of articulating AFOs. The clinical difference between these
      groups was the presence of equinus during stable standing while barefoot for
      patients aided by AFOs, whereas the second group remained plantigrade barefoot.
      We conclude that children with spastic diplegia with uncontrolled dynamic equinus
      benefit from the use of articulating AFOs for the movement of sit-to-stand.

PMID- 9150029
TI  - Comparative study of conventional hip-knee-ankle-foot orthoses versus
      reciprocating-gait orthoses for children with high-level paraparesis.
AB  - We evaluated eight children with thoracic or high lumbar-level paraparesis for
      metabolic performance while ambulating with custom fabricated thermoplastic hip
      knee-ankle-foot orthoses (HKAFOs) and reciprocating-gait orthoses (RGOs). Seven
      of the eight children had myelomeningocele. Each patient was tested in both
      systems at self-selected speeds in a crossover study design. At self-selected
      speeds, the level of exercise intensity for both thoracic and high-lumbar
      patients with either orthosis was lower than that for normal children. The
      average metabolic cost of walking in the RGO was twice that of normal children,
      as compared with six times normal in HKAFOs. For the four thoracic-level
      patients, there was a significantly higher oxygen cost of ambulation in using
      HKAFOs versus RGOs. No significant difference in metabolic performance was found
      for the high-lumbar patients. Velocity of ambulation was faster in the RGOs than
      in the HKAFOs. For thoracic-level patients, our data suggest that an RGO will
      provide a faster, more energy-efficient gait than a statically locked HKAFO. For
      high-lumbar patients, no significant difference was found between the two
      orthoses. Seven of eight children preferred the RGO over the HKAFO.

PMID- 9150030
TI  - Does gait continue to improve 2 years after selective dorsal rhizotomy?
AB  - Although changes in the gait pattern of children with spastic diplegia 1 year
      after selective dorsal rhizotomy have been well documented, minimal information
      exists regarding the continued changes in the gait pattern over time. Despite
      improvements in gait after rhizotomy, 66-75% of patients still require
      orthopaedic surgery for residual deformities. The optimal timing of the
      orthopaedic surgery after selective dorsal rhizotomy is not well established
      because of the lack of information regarding changes in gait over a long term.
      Using three-dimensional gait analysis, the gait pattern of 23 children was
      evaluated preoperatively, 1 and 2 years postoperatively. There were significant
      improvements in hip, knee, and ankle motion at 1 year after surgery. Although
      improvements in the gait pattern were found between 1 and 2 years after surgery,
      the changes were not significant. Therefore orthopaedic intervention may be
      undertaken at 1 year after rhizotomy to enhance function, as changes in gait from
      1 to 2 years after rhizotomy are minimal.

PMID- 9150031
TI  - The evolution of gait in childhood and adolescent cerebral palsy.
AB  - A longitudinal study over a mean of 32 months was conducted on 18 subjects with
      spastic diplegia, ranging in age from 4 to 14 years. Three-dimensional gait
      analyses were performed to compare the temporal and kinematic data across the two
      time intervals. The comparison revealed a deterioration of gait stability
      evidenced by increases in double support and decreases in single support with
      time and growth (p < 0.05). Kinematic analysis revealed a loss of excursion about
      the knee, ankle, and pelvis (p < 0.05). Additionally, passive range-of-motion
      analysis revealed a decrease in the popliteal angle over time (p < 0.05). In
      conclusion, this longitudinal investigation revealed that, in contrast to the
      gait of children with intact motor function, ambulatory ability tends to worsen
      over time in spastic cerebral palsy. Insight into the natural progression of gait
      function in cerebral palsy is essential when evaluating the change in motor
      status over time or the effects of an intervention in this population.

PMID- 9150032
TI  - Neonatal gangrene of the extremities.
AB  - Vascular insufficiency of a peripheral limb is a well-recognized and serious
      complication occurring in newborn infants. A 15-year review of a Level III
      neonatal intensive care unit at The Children's Hospital of Eastern Ontario
      revealed 10 infants who had a vascular insult to a limb necessitating the
      amputation of a portion of the limb. Predisposing factors to vascular occlusion
      were prematurity, polycythemia, umbilical artery catheterization, and intensive
      care treatment for other life-threatening illnesses. The lower extremity was most
      commonly affected, requiring below-knee amputations in two infants, knee
      disarticulation in one, and toe amputations in five. The remaining infants
      required an elbow disarticulation and amputation of the fingers, and one child
      had a massive ischemic contracture of the lower limb. Care should be taken not to
      amputate prematurely and await definitive demarcation of the gangrenous portion.
      Amputation should be designed to preserve growth plates wherever possible to
      ensure an adequate stump for prosthetic fitting in the older child.

PMID- 9150034
TI  - Progression of scoliosis.

PMID- 9150033
TI  - The pelvis of fetuses in the exstrophy complex.
AB  - By using a three-dimensional computed tomography (CT) scanner, we compared the
      anatomic features of the pelvis of three fetuses of same gestational age, one
      with a normal pelvis representing the reference model, one with classic bladder
      exstrophy, and one with cloacal exstrophy. The tomography slices were selected at
      the same levels for each case. Three angles expressing external opening of the
      pelvis were defined. Comparing normal and abnormal pelvises allowed definition of
      three criteria for the correction of the malformation: (a) the sum of the
      differential angles gives the amplitude of the correction needed; (b) a
      supraacetabular osteotomy appears to allow best closure of the pelvic ring; (c)
      only three slices of a CT scan are needed, which cannot be harmful, especially
      for neonates. Therefore, we believe that a CT scan of the pelvis should be
      performed whenever an osteotomy is planned in the surgical reconstruction of
      bladder and cloacal exstrophy.

PMID- 9150035
TI  - Relationship between molar root fusion and localized periodontitis.
AB  - We investigated the relationship between molar root fusion and localized
      periodontitis in this study. A total of 143 individuals (1,109 molars) aged 23 to
      68 years were examined for the presence of molar root fusion at diseased and
      healthy sites. Molar root fusions were diagnosed by periapical radiographs and
      clinical probing. Periodontal parameters measured included probing depth (PD),
      clinical attachment loss (CAL), gingival index (GI), and plaque index (PLI)
      around fused molars. Results indicated that the prevalence of molar root fusions
      in males and females was 15.2% (93/612) and 32.2% (160/497), respectively. The
      distribution of molars with root fusions occurs in the following order: maxillary
      second molars (51.8%), mandibular second molars (32.3%), maxillary first molars
      (5.7%), and mandibular first molars (0%). Statistically significant differences
      were observed between molar root fusions at healthy and diseased sites with
      respect to PLI, GI, PD, and CAL. The highest prevalence of molar root fusion was
      observed in females.

PMID- 9150037
TI  - Manifestations of insulin-dependent diabetes mellitus in the periodontium of
      young Brazilian patients. A 10-year follow-up study.
AB  - Eight female and 3 male patients from a group of 30 patients studied 10 years
      earlier and who had received no periodontal treatment during this period, in
      order to evaluate the progression of untreated periodontal disease in patients
      with insulin-dependent diabetes mellitus, were evaluated in terms of plaque
      accumulation, gingival inflammation, probing depth, and alveolar bone loss. The
      total number of dental surfaces that presented clinically detectable plaque
      deposits increased significantly (29% to 43%; P < 0.01; chi 2 = 46.36). Site
      specific comparisons for plaque index between studies showed a significant
      variation (P < 0.01) in the upper arch only for palatal surfaces and in the lower
      arch for the buccal and lingual surfaces. The total dental surfaces with inflamed
      surrounding gingiva increased from 11% to 33% in this study (P < 0.01; chi 2 =
      175.78). Site-specific comparison for gingival index showed a significant
      variation for all upper surfaces, while such difference for the lower arch was
      significant only for the buccal and lingual surfaces. The arithmetic means for
      the probing depth for the upper buccal, upper palatal, lower buccal, and lower
      lingual surfaces increased significantly (P < 0.01). The arithmetic means of
      alveolar bone loss also increased significantly for the upper posterior and lower
      regions (P < 0.01) and for the upper anterior and lower anterior regions (P <
      0.05). The correlation between age and probing depth was significant only for the
      upper palatal region (P < 0.01). The correlation between age and bone loss was
      significant only for the upper posterior region (P < 0.05). The results of this
      follow-up study suggest that despite little variation in plaque accumulation,
      gingival inflammation, probing depth, and bone loss increased after a 10-year
      interval in patients who had received no periodontal treatment during this
      period.

PMID- 9150036
TI  - Expression of extracellular matrix proteins in human periodontal ligament cells
      during mineralization in vitro.
AB  - Periodontal regeneration is a complex process that requires coordinated responses
      from several cell types within the periodontium. It is generally accepted that
      the periodontal ligament (PDL) has a heterogeneous cell population, where some of
      the cells may be capable of differentiating into either cementoblasts or
      osteoblasts. Thus, it has been hypothesized that PDL cells play a role in
      promoting periodontal regeneration. However, definitive evidence to support this
      concept is lacking. Previously, we reported that PDL cells induce
      biomineralization as determined by Von Kossa histochemistry and transmission
      electron microscopy. To further determine the osteoblast-like properties of PDL
      cells, human PDL cells were exposed to dexamethasone (DEX) in order to promote an
      osteoblast phenotype, and then cell activity monitored during mineral nodule
      formation in vitro. For mineralization studies, cells were cultured in DMEM
      containing 10% FBS and a) vehicle only; b) ascorbic acid (50 micrograms/ml) and
      beta-glycerophosphate (10 mM); or c) ascorbic acid, beta-glycerophosphate and DEX
      (100 nM) for 30 days. In addition, the effects of DEX on PDL cells in non
      mineralizing media were determined. Cells were stained weekly to evaluate mineral
      like nodules, using the Von Kossa method. Northern blot analyses for mRNA steady
      state levels for several bone-associated proteins, i.e., osteopontin (OPN), bone
      sialoprotein (BSP), alkaline phosphatase (ALP), osteocalcin (OCN), alpha
      2(1)(type 1) collagen and osteonectin (ON), were performed. DNA levels were also
      determined during the 30-day mineralization period. Under phase contrast
      microscopy, PDL cells in non-mineralizing media treated with DEX exhibited a more
      spindle-shaped morphology when compared with similar cells not exposed to DEX.
      Mineralizing conditions were required to induce mineral nodule formation.
      However, in this situation, mineral induction was independent of DEX; and
      furthermore, DEX-treated cells did not exhibit a different morphological pattern
      when compared with non-DEX treated cells. Mineral-like nodules were first seen at
      day 15, in concert with an increase followed by a decrease in expression of type
      I collagen and ON mRNA in both DEX-treated and non-treated cultures. Using
      Northern blot analysis for detection of specific proteins, we found that PDL
      cells did not express OPN, BSP, OCN, or ALP under any of the conditions used in
      this study. DEX did not alter DNA content in the cultures during the
      mineralization period. These results confirm that human periodontal ligament
      cells can be induced to mineralize in vitro and indicate that dexamethasone does
      not significantly alter the extent and pattern of mineralization.

PMID- 9150038
TI  - Important differences in clinical data from third, second, and first generation
      periodontal probes.
AB  - This study compared relative attachment levels (RAL) and probable crevice depths
      (PCD) from 6 periodontal probes (1 third, 4 second, and 1 first generation). A
      single clinician recorded RAL and PCD in 6 patients with chronic adult
      periodontitis (mean age 48.2 years) during two visits (interval: 1 week) using a
      Latin square examination order. Replicate measurements were recorded at the 4
      interproximal sites of the Ramford index teeth to examine intra-probe
      differences. Additional single measurements were recorded at similar sites of
      units 11, 26, 31 and 46 to investigate interprobe differences. Intra-probe RAL
      and PCD reproducibility was < or = 1 mm at > 94% of the sites. All intra-probe
      Pearson correlation coefficients were > 0.85 (P = 0.00). Inter-probe RAL and PCD
      agreement was < or = 1 mm at > 49% of the sites for RAL and > 61% of the sites
      for PCD. All inter-probe Pearson correlation coefficients were > 0.42 (P = 0.00)
      for RAL and > 0.49 (P = 0.00) for PCD. Analyses of variance showed significant
      differences in RAL and PCD between the first generation probe and the second
      generation probes (P < 0.005); in RAL between the third generation probe and the
      first and second generation probes (P = 0.0354); and in PCD between the third
      generation probe and the first and second generation probes (P = 0.0475). Inter
      probe differences were clinically significant in the recorded percentages of
      pockets > or = 4 mm and > or = 6 mm. Significant inter-probe differences were
      found in RAL and PCD which have clinical importance in data interpretation and
      comparison.

PMID- 9150039
TI  - Clinical and microbiological effects of subgingival antimicrobial irrigation with
      citric acid as evaluated by an enzyme immunoassay and culture analysis.
AB  - The purpose of the present study was to compare an enzyme immunoassay with
      culture samples from untreated and non-surgically treated periodontal pockets and
      to assess the clinical and microbiological effects of citric acid irrigation as a
      supplement to scaling and root planing. The enzyme immunoassay used in this study
      is a chairside diagnostic tool aimed at identifying the presence of P.
      gingivalis, P. intermedia, and A. actinomycetemcomitans. Six sites with pocket
      depths > or = 6 mm in each of 16 patients were monitored for 24 weeks using
      clinical and microbiological parameters. In two out of the six sites, scaling and
      root planing was supplemented with subgingival citric acid irrigation of the
      pocket after completion of the mechanical treatment. The sensitivity of the
      immunoassay in relation to culture was calculated to 85.5% and the specificity to
      90.2%. The immunoassay corresponded to a detection level of 10(4) as estimated by
      culture. Sites treated with a combination of scaling and irrigation with citric
      acid demonstrated a similar healing pattern as sites treated with scaling and
      root planing alone. The profile of the marker bacteria was almost parallel for
      the two groups. The results of this investigation thus indicated that the
      immunoassay can be used as a screening tool for selected periodontal pathogens
      and that adjunctive irrigation with citric acid has no measurable clinical or
      microbiological effects.

PMID- 9150040
TI  - The use of tetracycline-containing controlled-release fibers in the treatment of
      refractory periodontitis.
AB  - The purpose of this study was to evaluate the safety and clinical efficacy of
      controlled-release tetracycline-containing fibers in patients with refractory
      periodontitis versus the preceding classical treatment. One hundred twenty-one
      sites in 20 patients were followed from baseline to 6 months after fiber
      insertion. Each selected site was > or = 5 mm deep and bled on probing. All 20
      patients had at least one site > or = 7 mm which bled on probing. Those pockets
      remained after intense and repeated conventional therapy (scaling and root
      planing and often surgery), often including the use of systemic antibiotics. This
      treatment period, the so-called control period, preceded the experimental period
      by at least 3 years, when the fibers were placed. Both treatments (in control and
      test period) were performed in the Department of Periodontology at the University
      Hospital in Leuven. At the start of the experimental period, all pockets > or = 5
      mm were treated by the placement of fibers impregnated with 25% tetracycline. The
      fibers were removed after 10 days. Probing depth, clinical attachment level,
      gingival recession, and bleeding on probing were recorded at baseline, and at 1,
      3, and 6 months following treatment. Analysis of data from all sites indicated
      that a significant decrease in probing depth and gain in attachment were present
      at all follow-up visits. The mean probing depth reduction for sites > or = 7 mm
      was 3.2 mm at month 6, with a gain in attachment of 2.7 mm, while this was -1.0
      mm and -1.9 mm, respectively, during the preceding control period. The fraction
      of bleeding pockets was reduced from 77% to 27% and from 80% to 77% during the
      experimental and control periods, respectively. No significant adverse side
      effects were observed, except for a transient redness at fiber removal in 2
      sites. Fiber insertion appeared to be time-consuming even when the operator was
      familiarized with the procedure. The results of this study prove that
      tetracycline-impregnated fibers can reduce probing depth significantly for a
      period of 6 months in patients not responding to thorough and repeated classical
      periodontal treatment.

PMID- 9150041
TI  - Blur reduction of conventional film-based tomograms for pre-surgical evaluation
      of potential mandibular implant sites.
AB  - The usefulness of motion-based cross-sectional tomography to evaluate osseous
      support and adjacent anatomical structures for dental implant placement is
      limited by the inherent blurring in these images. The goal of this study was to
      develop a method to remove blurring while permitting accurate dimensional
      analysis of the potential implant site. Defined regions (anterior, cuspid,
      premolar, molar) on two preserved human mandibles were imaged using cross
      sectional linear tomography. Algorithms were developed as a personal computer
      application to remove the blur and to aid in identification of the cortical plate
      borders and the mandibular canal. The data set of eight tomograms was digitized
      and the blur reduced with the developed algorithm. An operator measured the
      height and width of the mandible on each original tomogram and each deblurred
      tomogram in triplicate. Method error was calculated as the difference between
      direct caliper measurements of the respective skull regions and image
      measurements of height and width for both the original digitized tomograms and
      the deblurred tomograms. Method error using the original images (height: -2.72 +/
      2.15 mm; width: -0.58 +/- 1.36 mm) compared to the deblurred tomograms (height: 
      0.58 +/- 1.16 mm; width: 0.37 +/- 0.59 mm) was significantly greater for both
      height (t-test level of significance, P = 0.0047) and width (t-test level of
      significance, P = 0.0001). These findings suggest that the method developed may
      greatly improve the ability of clinicians to accurately assess the implant site
      using cross-sectional film-based linear tomograms.

PMID- 9150042
TI  - Exocellular phospholipase C activity from a Propionibacterium acnes strain
      isolated from a periodontal pocket.
AB  - The culture supernatant of a strain of Propionibacterium acnes was investigated
      for its phospholipase (PL) activity. The microorganism was isolated from a
      periodontal pocket of a patient with periodontal disease. Supernatants from
      cultures of this microorganism were used as a source to obtain enzymes. Proteins
      from the supernatants were concentrated, and their enzymatic activity was
      partially purified through molecular sieving. The procedure yielded two peaks of
      activity. This activity was shown to hydrolyze phosphatidyl choline (PC) and
      phosphatidyl ethanolamine (PE) and was effective in a pH range of 5 to 9, with an
      optimal activity at pH 7.0. Divalent cations were not required for activity of
      the enzymes. Analysis of the products obtained from the hydrolysis of PC labeled
      in the choline, phosphoryl, or acyl moieties and PE containing labeled oleic acid
      indicated that the supernatants' activity was mostly phospholipase C (PL-C).
      Phospholipase C can act synergistically with other factors to produce tissue
      damage, and hence may contribute to the pathogenesis of periodontal disease.

PMID- 9150044
TI  - Recurrent peripheral giant cell granuloma associated with cervical resorption.
AB  - A case of recurrent peripheral giant cell granuloma in a 38-year-old man is
      reported. The lesion was localized on the attached gingiva of the lower left
      second premolar (tooth #35). The surgical excision of the lesion revealed a
      superficial resorption of the cervical region of the involved tooth. The
      resorption was smoothed out, and there was no sign of recurrence or further
      resorption after 14 months. Root resorption, although extremely rare, may be
      associated with peripheral giant cell granuloma.

PMID- 9150043
TI  - Myofibroblasts in phenytoin-induced hyperplastic connective tissue in the rat and
      in human gingival overgrowth.
AB  - Phenytoin is a commonly used anticonvulsant drug for the prevention of seizures.
      A common side effect of phenytoin (PHT) therapy is connective tissue hyperplasia,
      particularly in the oral cavity manifesting as gingival overgrowth. Our previous
      studies concerning the molecular mechanisms of drug-induced gingival overgrowth
      have demonstrated that PHT alters the normal tissue turnover/wound healing signal
      by causing changes in macrophage phenotype, resulting in the upregulation of
      essential polypeptide growth factors such as platelet-derived growth factor
      (PDGF). The cellular consequences of this elevation in growth factor have not
      been investigated. The present light and electron microscopic study of rat
      hyperplastic connective tissue and human gingival overgrowth induced by PHT
      treatment revealed the presence of numerous myofibroblasts. Cells identified as
      myofibroblasts were evident in all PHT-treated tissue samples and were
      characterized by an elongated fusiform cell shape, abundant cytoplasmic rough
      endoplasmic reticulum/polyribosomes, and accumulations of sub-plasmalemmal
      microfilaments containing spindle densities. These cells were never observed in
      control tissues. Myofibroblasts are associated with the later stages of tissue
      turnover, specifically with the transition from the granulation to the remodeling
      phases of the wound healing process. The presence of myofibroblasts in
      hyperplastic connective and gingival tissues induced by PHT treatment suggests
      that PHT exacerbates the normal tissue turnover/wound healing signals responsible
      for the appearance of myofibroblasts.

PMID- 9150045
TI  - Experimentally induced periodontitis in beagle dogs causes rapid increases in
      osteoclastic resorption of alveolar bone.
AB  - This study was undertaken to observe osteoclast differentiation related to
      inflammatory progression in aggressive periodontitis induced in beagle dogs by
      ligature of the gingival sulcus. To monitor osteoclastic activity, we used
      histochemical methods (staining for tartrate-resistant acid phosphatase [TRAP])
      to visualize osteoclasts and their TRAP-positive precursors and biochemical
      methods (ELISA assay of pyridinium crosslinks) to detect bone matrix degradation
      products in gingival crevicular fluid (GCF), serum, and urine. For histochemical
      study, tissue specimens were prepared from 3 adult female beagle dogs induced
      with experimental periodontitis by silk ligature placement below the gingival
      margin of mandibular molars ligated for 3, 7, and 21 days. For biochemical study
      for pyridinoline measurement, the 24 mandibular molars of 4 male beagle dogs were
      ligated. GCF, urine, and serum were collected at day 0 and at 3, 7, 14, and 21
      days after ligation. In the early inflammatory phase of ligature-induced
      periodontitis (day 3), TRAP+ mononuclear and TRAP+ multinucleated cells were
      present in the gingival connective tissue, and active bone-resorbing cells were
      found in excavated lacunae at the alveolar crest, but osteoclasts were not
      infiltrating the periodontal ligament during this early phase. During later
      stages of the inflammatory process (7 and 21 days), osteoclasts appeared at both
      the gingival and ligament side of the alveolar bone. Osteoclastic bone resorption
      appeared to be more severe on the bone surface at the gingival side than on the
      bone surface of the periodontal ligament side. Measurement of pyridinoline
      significantly increased in GCF and urine 3 days after ligation. The results
      suggested that bone at the crest of the alveolar bone is rapidly resorbed within
      3 days of inducing experimental periodontitis.

PMID- 9150046
TI  - Report of a gingival "surgical cyst" developing secondarily to a subepithelial
      connective tissue graft.
AB  - The subepithelial connective tissue graft is a valuable technique used to cover
      exposed root surfaces or to increase the zone of attached gingiva. Cysts, such as
      the gingival cyst of the adult, are epithelial-lined cysts which may arise from
      heterotropic glandular tissue, a proliferating rete peg, remnants of the dental
      lamina, or traumatic implantation of epithelial tissue. In this paper, a case
      report is described of a "surgical cyst" or cystic morphogenesis of surgically
      implanted epithelium developing secondarily to a subepithelial connective tissue
      graft.

PMID- 9150047
TI  - Mental illness--treatable illness.

PMID- 9150048
TI  - Menopause a life stage, not an illness.

PMID- 9150049
TI  - Peplau history project.

PMID- 9150050
TI  - Former First Lady speaks out on mental health care.

PMID- 9150051
TI  - 'Free to be' peer group supports patients with MPD/DD.
AB  - 1. During the last decade, dissociative identity disorder increasingly has been
      recognized as a relatively common post-traumatic syndrome. 2. Individuals with
      MPD/DD often are estranged from abusive families and have difficulty with social
      connection; an urgent therapeutic task is the re-creation of a sense of human
      interdependency and community. 3. Group therapy can be a useful and successful
      adjunct to individual psychotherapy for relatively stable clients with MPD/DD;
      the group's focus should be here-and-now, supportive, and psychoeducative in
      nature.

PMID- 9150052
TI  - Bridging the chasm: incorporating the medically compromised patient into
      psychiatric practice.
AB  - 1. In response to health care reform, psychiatric nursing has identified an
      expanded role that includes providing care to patients with complex health
      problems. 2. Conceptual changes of role responsibilities and time commitments to
      individual and milieu care are vital in supporting a change in the traditional
      psychiatric milieu. 3. Acknowledging and helping staff accept the
      unpredictability of certain medical conditions is key to success in providing
      quality integrated care to the medically compromised psychiatric patient.

PMID- 9150053
TI  - 'Talk to me' patient communication in a long-term care facility.
AB  - 1. Staff are important facilitators for communication among elderly patients, who
      often are alone and bored for long periods. 2. Staff serve as an essential link
      between the patients and the outside world, and serve as a conduit for initiating
      contact between residents. 3. Environment--including the selection of roommates,
      the proximity of residents, and the volume of radios and televisions--may greatly
      alter residents' ability to communicate.

PMID- 9150054
TI  - "As a young girl, I... " the benefits of narrational relationships in the lives
      of older residents.
AB  - 1. Using story telling with the older resident provides an opportunity for the
      nurse to demonstrate caring, and a common reality between them is developed. 2.
      Story telling by older residents, far from merely "living in the past," can
      promote their health and well being. 3. In the narrational relationship between
      nurse and older resident, story telling is encouraged and supported; for the
      nurse, this means valuing oneself, older adults, and story telling.

PMID- 9150055
TI  - Once upon a time... therapeutic stories as a psychiatric nursing intervention.

PMID- 9150056
TI  - Catastrophic consequences secondary to psychotropic drugs, Part 2.

PMID- 9150057
TI  - AAPHD turns 60--back to the future: whatever became of dental public health?

PMID- 9150058
TI  - Prevalence and distribution of dental restorative materials in US Air Force
      veterans.
AB  - OBJECTIVES: Millions of restorative procedures are performed annually in the
      United States, yet very little is known about their distribution in the general
      population. With increasing concern about potential adverse health effects of
      some restorative materials, a better understanding of the extent of exposure to
      these materials in the population is important. The purpose of this study is to
      report the prevalence, patterns, and distribution of dental restorative materials
      in a population of male veterans. METHODS: This collaborative study with the US
      Air Force examined 1,166 male veterans to assess exposure to dental amalgam and
      other restorative materials. An inventory of dental materials in the study
      population was obtained through oral examinations. Dental materials were
      classified into five categories: (1) amalgam; (2) resin; (3) porcelain, cement,
      or temporary, including ionomer (PCT); (4) cast gold alloys/direct filling gold;
      and (5) other metals (OM). The mean age of the study participants was 52.9 years.
      Over 94 percent of the study participants were dentate. RESULTS: The study
      participants averaged 45.8 restored/replaced surfaces. Restored/replaced surfaces
      increased with age while the number of teeth decreased with age. The most
      frequently used restorative material was amalgam, averaging 19.89 surfaces per
      subject, followed by PCT (9.38), resins (8.99), OM (5.52), and gold (4.91). The
      distributions of restorative materials varied by age, arch type, and location in
      the mouth. CONCLUSION: The study population experienced substantial exposure to
      dental materials.

PMID- 9150059
TI  - Restorative treatments received by children covered by a universal, publicly
      financed, dental insurance plan.
AB  - OBJECTIVES: This study sought to identify risk markers associated with the
      provision of new restorations in children and to investigate whether the carious
      status of a tooth surface is associated with the restorative decisions of
      dentists. METHODS: A total of 911 schoolchildren in grades one, two, and three
      were randomly selected from the island of Montreal, Quebec, Canada. Dental
      examinations were carried out in 1990, 1991, and 1992. Tooth surfaces of first
      permanent molars were classified as sound, noncavitated, and cavitated. The
      carious status of a tooth was matched with restorative decisions reported to the
      insurance board. RESULTS: The presence of a carious cavity was a strong risk
      marker for placement of new restorations (odds rations > or = 4.11). After one
      year, less than 2 percent of sound tooth surfaces of first permanent molars were
      restored and about 21 percent of noncavitated tooth surfaces were restored. When
      new class I restorations placed in maxillary first permanent molars within 3-6
      months after the baseline examination were evaluated, we found that between 73
      percent and 86 percent of these new restorations were placed in sound or
      noncavitated tooth surfaces. A similar trend also was observed in mandibular
      first permanent molars. Poor agreement between epidemiologic diagnosis and
      restorative decisions was found. The restorative profile of dentists was a
      significant risk marker for placement of new restorations. CONCLUSION: The
      majority of new restorations in first permanent molars were placed in sound and
      noncavitated tooth surfaces because of the ubiquitous prevalence of these tooth
      surfaces and the validity problems of current caries diagnosis methods.

PMID- 9150060
TI  - Factors influencing the appropriateness of restorative dental treatment: an
      epidemiologic perspective.
AB  - OBJECTIVES: An epidemiology analysis was performed to identify patient and
      dentist factors influencing over- and undertreatment of restorative services in a
      sample of insured adults. METHODS: At baseline, 681 Washington State employees
      and their spouses, aged 20 to 34 years and residing in the Olympia or Pullman
      areas, were interviewed by telephone. Oral assessments were conducted to measure
      personal characteristics, oral disease, and restoration quality. Adults were
      followed for two years to measure use of restorative services from dental
      insurance claims. Each adult's baseline and claims data were linked with provider
      and practice variables collected from the dentist who provided treatment.
      RESULTS: For overtreatment, 39 percent of adults received one or more replacement
      restorations in nondecayed teeth with satisfactory fillings at baseline, while 18
      percent of adults had one or more restorations placed in teeth with no decay and
      fillings. An adult's probability of overtreatment was higher if the adult had
      more fillings at baseline, or if an adult's dentist was younger, had a busy
      practice, advertised, charged higher fees, had less continuing education, or had
      a solo practice. For undertreatment, about 16 percent of adults either received
      no replacement restorations in teeth with unsatisfactory fillings at baseline, or
      had decayed teeth at baseline that were not filled or crowned. An adult's
      probability of undertreatment was higher if an adult had less decayed or more
      missing surfaces at baseline, or if an adult's dentist believed in sharing
      information with patients, had a busy practice, or reported not placing fillings
      when radiographic evidence of new caries was present. CONCLUSIONS: A minority of
      adults aged 20 to 34 experienced potential over- or undertreatment of restorative
      services, which are influenced by both patient and dentist factors.

PMID- 9150061
TI  - Factors related to loss of root canal filled teeth.
AB  - OBJECTIVES: This case-control study characterized factors related to loss of root
      canal filled (RCF) teeth among members of the Kaiser Permanente Dental Care
      Program, a dental health maintenance organization based in Portland, Oregon.
      METHODS: Individuals were identified who were enrolled continuously from January
      1, 1987, through December 31, 1994, underwent initial root canal therapy on a
      permanent tooth (excluding third molars) in 1987 or 1988, had a clinical
      examination within two years after endodontic access, and were at least 21 years
      old at access. Patients who lost the RCF tooth by December 31, 1994, were defined
      as cases (n = 96); those who did not were defined as controls (n = 120).
      Computerized data, dental radiographs, and chart entries were reviewed to
      ascertain variables of interest, and multivariable logistic regression was used
      to describe differences between the groups. RESULTS: RCF teeth of cases had fewer
      proximal contacts at access than RCF teeth of controls (odds ratio = 2.7; 95% Cl
      = 1.4, 5.1). Cases were older (odds ratio = 1.4; 95% Cl = 1.1, 1.9 per 10-year
      increase) and more likely to have had a facial injury than controls (odds ratio =
      3.6; 95% Cl = 1.2, 10.5). Cases also had more missing teeth (odds ratio = 1.5;
      95% Cl = 1.0, 2.1) and more plaque (odds ratio = 1.7; 95% Cl = 1.0, 2.6).
      CONCLUSIONS: Conditions evident during treatment planning may help dentists
      assess patients' chances of losing an RCF tooth.

PMID- 9150062
TI  - Dissatisfaction with oral health status in an older adult population.
AB  - OBJECTIVES: The aim of this study was to assess dissatisfaction with oral health
      in an older adult population and to identify factors associated with
      dissatisfaction. METHODS: Data were obtained from 907 community-dwelling older
      adults aged 50 years and older using personal interviews and clinical
      examinations. Bivariate and multivariate analyses examined the relationships
      among dissatisfaction with oral health and a variety of sociodemographic
      variables, clinical oral health measures, and measures of the functional and
      psychosocial impact of oral disorders. RESULTS: Overall, 14.3 percent of
      respondents were dissatisfied with their ability to chew, 21.6 percent with their
      dental appearance, and 5.6 percent with their ability to speak clearly. Almost
      one-third (30.8%) were dissatisfied with at least one of these dimensions of oral
      health. Edentulous subjects were more likely to be dissatisfied than dentate
      subjects. The multivariate regression model for dentate subjects contained seven
      variables that explained 31 percent of the variance in dissatisfaction scores.
      For the edentulous, the model contained three variables that accounted for 53
      percent of the variance. CONCLUSIONS: These results suggest that demographic,
      clinical, and psychosocial impact variables are associated with dissatisfaction
      with oral health. However, psychosocial impact variables had by far the strongest
      independent effect.

PMID- 9150063
TI  - Evaluation of bias and logistics in a survey of adults at increased risk for oral
      health decrements.
AB  - OBJECTIVES: Designing research to include sufficient respondents in groups at
      highest risk for oral health decrements can present unique challenges. Our
      purpose was to evaluate bias and logistics in this survey of adults at increased
      risk for oral health decrements. METHODS: We used a telephone survey methodology
      that employed both listed numbers and random digit dialing to identify dentate
      persons 45 years old or older and to oversample blacks, poor persons, and
      residents of nonmetropolitan counties. At a second stage, a subsample of the
      respondents to the initial telephone screening was selected for further study,
      which consisted of a baseline in-person interview and a clinical examination. We
      assessed bias due to: (1) limiting the sample to households with telephones, (2)
      using predominantly listed numbers instead of random digit dialing, and (3)
      nonresponse at two stages of data collection. RESULTS: While this approach
      apparently created some biases in the sample, they were small in magnitude.
      Specifically, limiting the sample to households with telephones biased the sample
      overall toward more females, larger households, and fewer functionally impaired
      persons. Using predominantly listed numbers led to a modest bias toward selection
      of persons more likely to be younger, healthier, female, have had a recent dental
      visit, and reside in smaller households. Blacks who were selected randomly at a
      second stage were more likely to participate in baseline data gathering than
      their white counterparts. Comparisons of the data obtained in this survey with
      those from recent national surveys suggest that this methodology for sampling
      high-risk groups did not substantively bias the sample with respect to two
      important dental parameters, prevalence of edentulousness and dental care use,
      nor were conclusions about multivariate associations with dental care recency
      substantively affected. CONCLUSIONS: This method of sampling persons at high risk
      for oral health decrements resulted in only modest bias with respect to the
      population of interest.

PMID- 9150064
TI  - Nonresponse bias in a survey of Ontario dentists' infection control and attitudes
      concerning HIV.
AB  - OBJECTIVE: This study investigated late response and nonresponse bias in an HIV
      related survey of dentists. METHODS: Questionnaires with ID numbers were mailed
      to all dentists in Ontario (N = 5,997) with additional mailings four and seven
      weeks later. RESULTS: Proportionately more respondents who returned
      questionnaires less than four weeks after the first mailing reported that they
      knowingly treated (P < .05) or were willing to treat HIV-infected patients (P <
      .05); that they had an accurate perception of risk of HIV infection after a
      needlestick injury (P < .01), and preferred not to refer HIV-infected patients (P
      < .01). Linear extrapolation of cumulative percent responses indicated
      nonresponse bias in terms of attitude and knowledge items; however, the magnitude
      was low. CONCLUSIONS: The effects of late response and nonresponse bias on the
      results of this study were small. However, these results cannot be generalized
      beyond the study population, and obtaining high response rates and testing for
      nonresponse bias in surveys of attitudes related to HIV are recommended.

PMID- 9150066
TI  - Making original data from clinical studies available for alternative analysis.

PMID- 9150065
TI  - The potential of bone marrow stem cell transplantation in the treatment of
      autoimmune diseases.

PMID- 9150067
TI  - Outcome versus activity in rheumatoid arthritis: a focus blurred.

PMID- 9150068
TI  - Prospectively measured red cell folate levels in methotrexate treated patients
      with rheumatoid arthritis: relation to withdrawal and side effects.
AB  - OBJECTIVE: To investigate whether red cell folate (RCF) levels relate to side
      effects, withdrawals, or disease activity during treatment with the folic acid
      antagonist methotrexate (MTX) for rheumatoid arthritis (RA). METHODS: Side
      effects were recorded monthly, RCF levels were measured by lactoglobulin binding
      radioassays, and 8 variables for disease activity were measured in a placebo
      controlled double blind trial of 28 weeks' duration comparing efficacy of MTX (n
      = 23) and D-penicillamine (n = 23). RESULTS: From Week 20 RCF levels decreased
      only in the MTX group (p < 0.02), and 5 MTX treated patients withdrew due to side
      effects. Withdrawals had lower RCF values at Weeks 0 and 9 compared to the
      remaining patients (p < 0.05). Folate deficiency evolved in 5 patients; 2 of
      these developed cytopenia. Aberrations in the scheduled dosage increase were
      related to lower pretreatment values of RCF (p = 0.007). Side effect scores were
      inversely correlated to RCF values at Weeks 0, 9, and 28 (p < 0.05). RCF levels
      measured concomitantly with liver enzyme elevation were lower than the remaining
      values (p < 0.001). When side effects were reported, 96% of concomitantly
      measured RCF values were below 800 nmol/l. RCF values at entry did not correlate
      to improvement in any variable for disease activity, or a graded overall
      improvement. CONCLUSION: RCF levels decrease during MTX treatment and relate to
      side effects, withdrawals, liver enzyme elevations and aberrant MTX dosage
      increase, but not to the therapeutic effect. RCF above 800 nmol/l protects
      against side effects.

PMID- 9150069
TI  - Response to therapy in rheumatoid arthritis is influenced by immediately prior
      therapy.
AB  - OBJECTIVE: Clinicians do not often employ washout periods before prescribing a
      change in therapy for rheumatoid arthritis (RA). As a result, the observed
      effectiveness or lack of effectiveness of a new drug actually represents the
      effectiveness of that drug had the patient been taking placebo minus the residual
      effectiveness of the old drug. METHODS: We studied new starts of selected disease
      modifying antirheumatic drugs (DMARD) and prednisone in 2,898 patients with RA
      from 8 ARAMIS data bank centers, broken into subgroups on the basis of
      immediately prior therapy. Therefore, we examined the hypothesis that the chances
      of a treatment being observed effective depend upon the immediately preceding
      treatment. Using intent-to-treat analysis, we analyzed the effects upon Health
      Assessment Questionnaire (HAQ) disability and pain scores an average of 9 months
      after the new drug start. RESULTS: Methotrexate reduced disability significantly
      except after intramuscular gold or hydroxychloroquine and it reduced pain
      significantly after all prior therapies. Hydroxychloroquine reduced disability
      significantly after nonsteroidal antiinflammatory drugs (NSAID) only, but
      disability increased after intramuscular gold; pain was decreased only after
      NSAID only. Prednisone had no consistent effect upon disability but was
      consistently associated with decreased pain. Greatest effectiveness was always
      seen with a new drug start after NSAID only treatment versus after DMARD
      treatment. CONCLUSION: The effectiveness of a newly started RA treatment after 9
      months may be substantially influenced by immediately prior treatment. This
      finding provides an additional reason for concern about direct extrapolation of
      clinical trial data into clinical practice.

PMID- 9150070
TI  - Lack of pharmacokinetic interaction of meloxicam with methotrexate in patients
      with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the pharmacokinetic interaction of oral meloxicam with
      intravenous (i.v.) methotrexate (MTX) in patients with rheumatoid arthritis (RA).
      METHODS: Thirteen patients with RA received MTX 15 mg i.v. in the absence of
      nonsteroidal antiinflammatory drugs (NSAID) and after one week in the presence of
      steady state levels of meloxicam. Plasma concentrations of MTX and meloxicam were
      determined using validated high performance liquid chromatography methods. One
      patient did not complete the study. The interaction of meloxicam and MTX was
      examined by equivalence testing. The endpoints AUCMTX, VssMTX, CltotMTX, and
      CmaxMTX were analyzed parametrically, whereas endpoints MRTMTX, CltotMTX,
      t1/2MTX, and tmaxMTX were analyzed nonparametrically. RESULTS: The MTX plasma
      concentrations over time, with and without meloxicam, did not differ
      significantly. The point estimator for the ratio of log transformed data of the
      primary endpoint AUCMTX was 108%; the lower 95% confidence limit was 100% and the
      upper 95% confidence limit was 117%. Clinical laboratory values and adverse
      events revealed no increased MTX toxicity during concomitant treatment with
      meloxicam. CONCLUSION: In this short term interaction study there was no
      statistically significantly effect of meloxicam on the pharmacokinetics of MTX.
      The combination of MTX and meloxicam did not lead to increased MTX toxicity.

PMID- 9150072
TI  - HLA typing in a large family with multiple cases of different autoimmune
      diseases.
AB  - OBJECTIVE: Because of the concurrence, in members of one family, of different
      autoimmune disorders [rheumatoid arthritis (RA), systemic lupus erythematosus
      (SLE), psoriasis (PS), and inflammatory bowel disease (IBD)], we investigated the
      genotypes of each member and compared the results with current knowledge of
      genetic inheritance of rheumatic and other autoimmune diseases. METHODS: Sera and
      peripheral blood lymphocytes of 16 family members were collected for HLA typing
      and investigation. RESULTS: All patients with RA were DR4 positive ad 4 of 5
      showed the maternal A2B51DR4 haplotype. Two of 3 siblings with the genotype HLA
      A2/3, B8/35, DR2/3 had SLE. Patients with IBD and psoriasis shared the haplotype
      HLA-A3, B35 CW4 DR2. CONCLUSION: The results show that the important role of
      patients, sex and confirm the association between HLA haplotype and RA or SLE.
      They support the hypothesis that autoimmunity is a mendelian dominant trait, and
      that secondary genes, including these of the major histocompatibility complex,
      confer phenotypic specificity.

PMID- 9150071
TI  - HLA-DRB1, DQA1, and DQB1 genotypes and risk of vasculitis in patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the association of rheumatoid vasculitis (RV) with the
      expression of the shared epitope, HLA-DRB1*04, DQA1, and DQB1 alleles. METHODS: A
      case-control study was designed to compare the frequency of the shared epitope,
      DRB1*04 alleles, DQA1, and DQB1 alleles of 31 patients with RV with that of 76
      patients with rheumatoid arthritis (RA) without vasculitis. RV cases were
      discerned in subgroups according to presence or absence of minor skin vasculitis
      and major organ lesions. HLA-DRB1, DQA1, and DQB1 typing was performed by a
      polymerase chain reaction amplification and oligonucleotide hybridization.
      RESULTS: Overall, no associations were found between RV and the shared epitope,
      the DRB1*04 alleles, DQA1, or DQB1 alleles. The risk of developing RV with minor
      skin vasculitis (i.e., purpura or petechiae) was 10-20-fold increased in patients
      with DRB1*04, in particular in those homozygous for DRB1*04, and also in those
      with DRB1*0401. No such association was found for patients with major organ
      lesions. CONCLUSION: The occurrence of vasculitis in RA is not associated with
      the shared epitope. DQA1, or DQB1 alleles. However, the risk of minor skin
      vasculitis is higher in patients carrying DRB1*04.

PMID- 9150073
TI  - Recombinant 52 kDa Ro(SSA) ELISA detects autoantibodies in Sjogren's syndrome
      sera that go undetected by conventional serologic assays.
AB  - OBJECTIVE: To determine the utility of a recombinant 52 kDa Ro(SSA) ELISA for
      detecting Ro autoantibodies in Sjogren's syndrome (SS) sera. METHODS: Several
      different groups of SS sera previously tested for Ro and La(SSB) autoantibodies
      in clinical diagnostic labs were tested by ELISA with a recombinant human 52 kDa
      Ro fusion protein. RESULTS: Five of 18 primary SS sera (28%) that had
      undetectable Ro and La autoantibodies by conventional immunodiffusion (ID) or
      ELISA in clinical diagnostic laboratories had significant reactivity with a
      recombinant 52 kDa Ro (r52) ELISA. On repeat testing these 5 sera were again
      negative for Ro and La antibodies by ELISA with purified 60 kDa Ro and La
      antigens, but 3 of these sera were reactive with r52 by immunoblot, and
      immunoprecipitated a 52 kDa protein from human cell extracts. Twelve of 12
      primary SS sera that had detectable Ro autoantibodies by ID also reacted with the
      r52 ELISA, whereas none of 11 normal sera and only one of 27 ID-defined Ro
      negative systemic lupus erythematosus sera did. Eleven of 28 sera from patients
      with suspected SS were Ro positive by ID and 60 kDa Ro ELISA. All 11 were also Ro
      positive by the r52 ELISA. Two of the 28 suspected SS sera were Ro positive by
      the r52 Ro ELISA, but were Ro and La negative by ID and 60 kDa Ro and La ELISA.
      CONCLUSION: Anti-52 kDa Ro autoantibodies are frequently present in primary SS
      sera, but may go undetected by commonly used Ro serologic assays. Our r52 ELISA
      is more sensitive in detecting Ro antibodies in SS than conventional ID and 60
      kDA Ro ELISA.

PMID- 9150074
TI  - Thrombocytopenic purpura as initial manifestation of systemic lupus
      erythematosus.
AB  - OBJECTIVE: To study the outcome of patients with idiopathic thrombocytopenic
      purpura (ITP) treated with splenectomy, with respect to the development of
      systemic lupus erythematosus (SLE). METHODS: Two independent observers reviewed
      data of 20 clinical, laboratory, and therapeutic variables of patients with ITP,
      with no clinical or laboratory indications of SLE, who were treated by
      splenectomy from 1952 to August 1995. 115 patients were studied, 86 female, 25
      male, mean age 31.5 (SD 15.4) yrs (range 10-75), who had a mean followup of 7.2
      (SD 7.5) yrs (range 0.08-32.8). RESULTS: 14 patients (12.1%) developed SLE. The
      most common SLE manifestations were arthritis (78.5%), lymphopenia (74.1%),
      mucocutaneous manifestations (64.2%), and hemolytic anemia (35.7%). Mortality was
      greater in the SLE group than in the ITP group (3 vs 4; odds ratio 6.61, 95%
      confidence interval 1.57-27.76, p = 0.037). 67% of the patients with ITP and
      57.2% with SLE were in complete remission at the last visit (p = 0.54).
      CONCLUSION: Almost one of 8 patients with splenectomy due to ITP developed SLE.
      These patients require periodic followup to monitor other clinical data of SLE.

PMID- 9150075
TI  - Serial analysis of autoantibody responses to the collagen-like region of Clq,
      collagen type II, and double stranded DNA in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To compare autoantibody responses to the collagen-like region of Clq
      (ClqCLR) with responses to double stranded DNA (dsDNA) and native rat collagen
      type II during changes of disease activity in patients with systemic lupus
      erythematosus (SLE). METHODS: IgG antibodies to ClqCLR, dsDNA, and collagen type
      II were determined by ELISA in serial samples from 33 patients with SLE with
      different disease manifestations. Antibodies to dsDNA were also detected with the
      Crithidia luciliae test. RESULTS: Distinct antibody responses in conjunction with
      flare were observed, but the markers were more clearly related to clinical groups
      and to severity of disease than to changes of disease activity. Anti-ClqCLR
      antibodies were detected in 2/10 patients with mild flares, 7/12 patients with
      severe extrarenal flares, and in 10/11 of the patients with active lupus
      glomerulonephritis. Findings with regard to anti-dsDNA antibodies were similar.
      Antibody responses to collagen type II were detected in 7/12 of the patients with
      severe extrarenal disease, and were less frequently found in the other patients.
      ELISA absorption and elution experiments with anti-ClqCLR antibodies in the
      patient sera did not suggest cross reactivity with collagen type II and dsDNA.
      CONCLUSION: Serial investigation of 33 patients with SLE showed that antibodies
      to ClqCLR and dsDNA are markers of severe SLE, particularly SLE with kidney
      involvement. Antibodies to collagen type II are possible markers of severe
      extrarenal SLE with vasculitis and serositis. Analysis of anti-ClqCLR antibodies
      provided no evidence of cross reactivity with collagen type II and dsDNA.

PMID- 9150076
TI  - Geographic variation in the prevalence of Raynaud's phenomenon: a 5 region
      comparison.
AB  - OBJECTIVE: To determine the population based prevalence of Raynaud's phenomenon
      (RP) in 5 geographic regions: one in South Carolina, USA, and 4 in France; to
      explore the relationship of RP to the climate; to investigate possible risk
      factors; and to describe the characteristics of RP+ subjects in the general
      population. METHODS: The study consisted of 2 phases: a telephone survey of a
      randomly drawn sample of households, with 10,149 completed interviews; these were
      followed by a face to face interview and clinical evaluation (n = 1,534),
      including diagnosis of RP. The same methodology was used in all 5 regions: for
      recruitment of subjects, criteria for RP, method of RP diagnosis, and for
      gathering additional information. RESULTS: The prevalence of RP was found to be
      related to the climate. The relationship between RP and climate was complicated,
      however, by the fact that many subjects had moved between climate zones. The
      relationship of RP to a cold climate became more evident after taking the
      migration patterns into account: the majority of RP+ subjects in the 2 coldest
      regions had lived all their lives in the same or a similar climate zone; the
      majority of RP+ subjects in the 2 warmest regions had previously lived in a
      colder climate. Other factors associated with RP were family history of RP,
      cardiovascular diseases, older age, a low body mass index, use of vibrating
      tools, and outings of a day or more. The classical triphasic RP was rarely
      encountered in the general population and the most frequently observed signs and
      symptoms during an RP attack were blanching accompanied by numbness. CONCLUSION:
      In addition to being a triggering factor for RP attacks, cold also appears to be
      an etiologic factor in the pathogenesis of RP. A subclinical cold injury, more
      likely to occur in colder climates, may be responsible for the "local fault" that
      has been implicated in the pathogenesis of RP and, in association with other risk
      factors, may predispose subjects to develop clinical RP.

PMID- 9150077
TI  - A peptide sequence from platelet factor 4 (CT-112) is effective in the treatment
      of type II collagen induced arthritis in mice.
AB  - OBJECTIVE: Platelet factor 4 (PF-4) is a critical alpha chemokine in inflammation
      and injury responses, with multiple effects upon cellular activities. Discrete
      peptide sequences of the PF-4 molecule have been shown to retain biological
      activity. Our aim was to examine the influence of the PF-4 derived octapeptide
      (CT-112; TTSQVRPR) on type II collagen induced arthritis in mice, to determine if
      this peptide exhibited antiinflammatory properties. METHODS: DBA/1 mice were
      treated with CT-112 from either the time of immunization with type II collagen or
      from the initial onset of arthritis. RESULTS: CT-112 both prevented the
      development of arthritis in mice treated prophylactically and reduced progression
      of disease in animals treated therapeutically, and was active when delivered by
      either subcutaneous injection or oral gavage. No marked immunosuppressive effects
      were observed during CT-112 treatment, with only moderate decrease in antibody
      levels and mitogen responses. A significant reduction of the circulating levels
      of IL-1 was a consistent finding in mice treated therapeutically with CT-112.
      CONCLUSION: These data suggest PF-4 derived octapeptide exerts antiinflammatory
      effects of experimental arthritis in mice.

PMID- 9150078
TI  - Routine molecular genotyping of HLA-B27 in spondyloarthropathies overcomes the
      obstacles of serological typing and reveals an increased B *2702 frequency in
      ankylosing spondylitis.
AB  - OBJECTIVE: To evaluate the reproducibility and reliability of polymerase chain
      reaction (PCR) in HLA-B27 typing compared to the conventionally used
      microlymphocytotoxicity test (MLCT). To determine the HLA-B27 subtype frequencies
      (B*2701-B*2709) in patients with HLA-B27 associated disease and healthy persons
      using sequence specific oligonucleotides (SSO). METHODS: 398 consecutive patients
      were HLA-B27 typed by MLCT and PCR. Subtyping by SSO was performed in 142
      patients with HLA-B27 associated disease [ankylosing spondylitis (AS) n = 38,
      reactive arthritis 44, undifferentiated spondyloarthropathy (uSpA) 45, psoriatic
      arthritis 15] and 125 healthy HLA-B27 controls. RESULTS: MLCT identified 61 HLA
      B27 positive patients (15.3%); PCR identified 78 positive patients (19.6%). MLCT
      gave false negative results for 8 patients (2.0%) and false positives for a
      further 7 (1.8%). Only subtypes B*2702 and B*2705 were present in patients and
      controls. Overall frequencies of B*2702 in patients and controls were 14.1 and
      9.6%, respectively. The B*2702 frequency was significantly (pcorr. < 0.04) higher
      in AS (23.7%) and lower in uSpA (6.7%) patients. CONCLUSION: HLA-B27 typing by
      PCR is reliable and reproducible and therefore recommended for routine typing. It
      overcomes the obstacles of serological typing, i.e., equivocal results and cross
      reactivity. In addition, subtype frequencies (B*2702 and B*2705) are equally
      distributed among patients and controls, although subtype B*2702 seems to be more
      frequent in AS and less so in uSpA.

PMID- 9150079
TI  - HLA-DRB1*08 influences the development of disease in Mexican Mestizo with
      spondyloarthropathy.
AB  - OBJECTIVE: HLA class II encoded factors may influence the phenotype of ankylosing
      spondylitis (AS). These include HLA DRB1*07 for peripheral arthritis, and
      polymorphism of the HLA-linked LMP2 locus and HLA DRB1*08 for acute anterior
      uveitis (AAU). We studied the relationship between DRB1*08 and disease phenotype
      in additional populations of individuals with AS. METHODS: The patient population
      included 385 unrelated HLA-B27 positive individuals with AS. These included 204
      Caucasians and 2 populations of Mexican Mestizo with AS: 106 with predominately
      adult onset disease from Guadalajara and 75 with predominately juvenile onset
      disease from Mexico City. The control population of 428 individuals included 210
      random and 36 HLA-B27 positive unrelated Canadian Caucasians and 173 random and 9
      HLA-B27 positive Mexican Mestizo from Mexico City. DRB1*08 typing was by sequence
      specific polymerase chain reaction. RESULTS: A significantly higher prevalence of
      DRB1*08 was observed in Mexican patients with juvenile onset disease (44.9%) and
      especially those with undifferentiated spondyloarthropathy (55.6%) compared to
      normal unrelated Mexican Mestizo (25.4%) (p < 0.01 for both) and in patients with
      undifferentiated spondyloarthropathy versus B27 controls (11.1%) (p = 0.03),
      although no significant differences were observed in within patient group
      comparisons based on phenotypic features of disease such as AAU and age at onset.
      No significant relationship between DRB1*08 and disease phenotype was evident in
      Caucasian individuals. CONCLUSION: Our data suggest DRB1*08 may influence the
      phenotype of spondyloarthritis in Mexican Mestizo, but do not support the view
      that DRB1*08 influences the development of AAU, as reported in a Japanese
      population.

PMID- 9150080
TI  - Socioeconomic status in ankylosing spondylitis: relationship between occupation
      and disease activity.
AB  - OBJECTIVE: To identify the socioeconomic status through occupation of a large
      cohort of patients with ankylosing spondylitis (AS) and to determine possible
      relationships between occupation and clinical variables. METHODS: We analyzed the
      employment status of 1,044 patients with AS. RESULTS: 85% of patients (890 of
      1,044) were in full employment at the time of the assessment compared to 15% who
      were unemployed. When 50 employed patients were compared to 50 unemployed cases,
      the latter had increased disease activity and lower psychosocial well being.
      CONCLUSION: Employed patients from the higher occupational group (I), had less
      disease activity, and lower pain and depression than patients from the lowest
      occupational group (IV).

PMID- 9150081
TI  - Secondary amyloidosis in ankylosing spondylitis. A systematic survey of 137
      patients using abdominal fat aspiration.
AB  - OBJECTIVE: To assess the frequency and clinical significance of amyloid deposits
      in abdominal fat in patients with ankylosing spondylitis (AS). METHODS: Abdominal
      subcutaneous fat aspiration (ASFA) by fine needle was performed in 137 unselected
      patients with AS of more than 5 years of disease evolution. A followup study was
      done of patients with amyloidosis in the abdominal fat (ASFA positive test) to
      evaluate the development of clinical amyloidosis. RESULTS: In 10 (9M/1F) patients
      with AS, the ASFA revealed amyloid deposits (prevalence of 7%). Patients with AS
      and an ASFA+ test were older and had more active and severe disease than those
      without AS. Only 2 ASFA positive test patients had clinical amyloidosis at the
      time of the test. After a followup period of 2-10 yrs (mean 5.4 +/- 3.2 yrs), 3
      more patients developed symptomatology due to amyloidosis. All 5 patients with
      clinical amyloidosis showed nephropathy, and proteinuria was found in each. The
      remaining patients did not develop clinical amyloidosis during followup.
      CONCLUSION: Amyloid deposits in abdominal fat are not a rare finding in AS. A
      significant proportion of these patients do not develop clinical amyloidosis
      after a followup of several years. Thus, an ASFA + test in patients with AS is
      not always associated with a poor prognosis at least in the short term, although
      longer followup is required.

PMID- 9150082
TI  - The therapeutic effects of tenidap in canine experimental osteoarthritis:
      relationship with biochemical markers.
AB  - OBJECTIVE: To define the dose-response relationship of the therapeutic effects of
      tenidap in experimental osteoarthritis (OA) and relate this to the effects on
      interleukin 1 (IL-1) and metalloprotease activity. METHODS: The anterior cruciate
      ligament of the right knee joints of 22 mongrel dogs were sectioned (ACLS)
      through a stab wound. Seven dogs received no treatment, 5 were treated with oral
      omeprazole (20 mg/day), another 5 were treated with oral tenidap (1.5 mg/kg bid)
      plus omeprazole (20 mg/day), and 5 received tenidap (0.5 mg/kg bid) plus
      omeprazole (20 mg/day). The dogs received medication for 8 weeks beginning 4
      weeks after surgery. All dogs were killed 12 weeks after surgery, except for
      those in the first group, which were sacrificed at 4 weeks. Lesions were
      evaluated macroscopically for the incidence and size of osteophytes and the area
      and grade of cartilage erosions on the condyles and plateaus, along with
      histologic evaluation of the severity of the cartilage lesions and synovial
      inflammation. Stromelysin, collagenase, and gelatinase activities were measured
      in cartilage and synovial membrane. Also, the level of IL-1 activity was measured
      in the synovial fluid. RESULTS: Dogs treated with tenidap at both 1.5 and 0.5
      mg/kg bid exhibited a reduction in the size of osteophytes (2.25 +/- 0.30 mm,
      1.70 +/- 0.65 mm, respectively) compared to the 12 weeks OA group (3.55 +/- 0.94
      mm). Tenidap also significantly decreased the size and/or grade or cartilage
      macroscopic lesions on both condyles and plateaus. This reduction was more
      pronounced in dogs treated with the higher drug dose. The histological severity
      of cartilage lesions on femoral condyles was reduced for both tenidap doses used
      and significance (p < 0.04) reached for the 1.5 mg/kg bid tenidap treated dogs.
      Tenidap markedly and significantly reduced the level of metalloprotease activity
      for all 3 enzymes tested in synovial membrane (stromelysin, p < 0.03;
      collagenase, p < 0.02; gelatinase, p < 0.03) and in cartilage (stromelysin, p <
      0.02; collagenase, p < 0.02; gelatinase, p < 0.03) with greater reduction, in
      general, in dogs treated with the higher dose of tenidap. IL-1 activity was
      significantly reduced (p < 0.02) only in animals treated with tenidap at 1.5
      mg/kg bid. CONCLUSION: This study confirms that tenidap is an effective anti
      osteoarthritic drug in this ACLS model where therapy was begun 4 weeks after
      surgery. We have defined doses that gave graded therapeutic effects, and under
      these conditions the effectiveness coincided with the suppression of IL-1 and
      metalloprotease activity, processes known to play a major role in the
      pathophysiology of OA lesions.

PMID- 9150083
TI  - Toe dactylitis in patients with spondyloarthropathy: assessment by magnetic
      resonance imaging.
AB  - OBJECTIVE: To investigate using magnetic resonance imaging (MRI) the part played
      by flexor and extensor tenosynovitis and synovitis of the metatarsophalangeal
      (MTP), proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints in
      producing the "sausage-like" aspect of spondyloarthropathy (SpA) toe dactylitis.
      METHODS: Twelve sausage-like toes and corresponding contralateral toes of 7
      consecutive patients meeting Amor criteria for SpA were studied by MRI. RESULTS:
      All dactylitic toes showed fluid collections in the flexor synovial sheaths on
      MRI. Due to the sheath distension the plantar bone to skin distance was
      significantly increased (p < 0.05) in the dactylitic toes compared to normal
      contralateral toes. Peritendinous soft tissues were not involved since these were
      significantly thicker (p < 0.05) in normal toes. Extensor synovial sheaths were
      involved in only 4 dactylitic toes. Of the 36 joints of the 12 dactylitic toes
      only 2 MTP joints showed capsule distension. Considering MRI as the "gold
      standard", examination showed 100% sensitivity and specificity for flexor sheath
      involvement but lacked sensitivity for extensor synovial sheaths and showed a low
      specificity for joint capsule distension. CONCLUSION: Like finger dactylitis, toe
      dactylitis may also be due to flexor tenosynovitis and synovitis of MTP, PIP, and
      DIP joints may not be a required condition for sausage-shaped appearance.
      Extensor tenosynovitis may be present in addition to flexor tenosynovitis.
      Physical examination is a sufficient method for diagnosing toe dactylitis.

PMID- 9150084
TI  - Corticosteroid responsive tenosynovitis is a common pathway for limited joint
      mobility in the diabetic hand.
AB  - OBJECTIVE: To test the hypothesis that diabetic tenosynovitis participates in the
      contractures of the syndrome of limited joint mobility (SLJM). METHODS: Adults
      with diabetes mellitus were referred for the evaluation of diabetic hand
      conditions. Patients with SLJM or diabetic trigger finger were studied after
      Dupuytren's contracture, hand neuropathy, carpal tunnel syndrome, and arthritis
      were excluded. A time series design was employed in which patients were observed
      for 3 mo to obtain a baseline, then the planar flexor tendon sheaths were
      injected with 10 mg of methylprednisolone acetate or 10 mg triamcinolone
      acetonide and were reassessed at 1, 3, and 12 mo. RESULTS: Response rates,
      defined by complete resolution of digital contractures and triggering after
      corticosteroid injection, were 94% (31/33), 76% 28/33), and 61% (17/29) at 1, 3,
      and 12 mo, respectively, which were all significantly different from preinjection
      (p < 0.001). Individual response rates for SLJM and trigger finger were similar.
      No appreciable differences between methylprednisolone acetate and triamcinolone
      acetonide were observed, although there was a trend for earlier recurrence with
      methylprednisolone. CONCLUSION: Corticosteroid injection is a safe and effective
      therapy that should be considered in patients with SLJM or diabetic trigger
      finger. The excellent response to injection indicates that diabetic tenosynovitis
      is a common pathway in diabetic hand conditions.

PMID- 9150085
TI  - Nonphysician practitioner treatments and fibromyalgia syndrome.
AB  - OBJECTIVE: Patients with fibromyalgia syndrome (FM) are high consumers of
      alternative medical interventions and frequently consult nonphysician
      practitioners. Although individuals may express satisfaction with alternative
      treatment methods, their effect upon symptoms and outcome of FM is not known. We
      compare symptom reporting and functional status in patients with FM being treated
      or not being treated by nonphysician practitioners. METHODS: 82 patients with FM
      enrolled in a cross sectional study were divided into current users (n = 33) and
      nonusers (n = 49) of nonphysician practitioner treatment over the preceding 6
      months. Included were treatments by physiotherapists and psychologists, as well
      as all categories of alternative practitioners. The measurements studied were a
      patient global assessment of disease severity on a 100 mm visual analog scale
      (VAS), a physician global assessment on a 100 mm VAS, the Health Assessment
      Questionnaire (HAQ), and the Fibromyalgia Impact Questionnaire (FIQ). RESULTS:
      There were no differences for the FIQ, HAQ, or patient or physician global
      severity scores for users and nonusers of nonphysician practitioner treatments.
      The total number of health care professional visits in the preceding 6 months was
      higher for users than nonusers (27.0 vs 9.3; p < 0.001), although physician
      visits did not differ (9.0 vs 9.3). CONCLUSION: Patients with FM who had been
      treated by nonphysician practitioners during the preceding 6 months reported
      similar pain and functional impairment to those not receiving treatments.

PMID- 9150086
TI  - Fibromyalgia syndrome (FM) and nonarticular tenderness in relatives of patients
      with FM.
AB  - OBJECTIVE: To determine the prevalence of fibromyalgia (FM) and to assess
      nonarticular tenderness in relatives of patients with FM. METHODS: Thirty female
      patients with FM randomly chosen from 117 of their close relatives (parents,
      brothers, sisters, children, husbands) were assessed for nonarticular tenderness.
      A count of 18 tender points was conducted by thumb palpation, and tenderness
      thresholds were assessed by dolorimetry at 9 tender sites. FM was diagnosed
      according to the 1990 American College of Rheumatology criteria. RESULTS: The
      prevalence of FM among blood relatives of patients with FM was 26%, and among
      their husbands 19%. FM prevalence in male relatives was 14%, and in female
      relatives 41%. The mean tender point counts of male and female young relatives
      was significantly higher than that of controls: 6.1 vs 0.2 (p < 0.01), and 4.4 vs
      0.4 (p < 0.01) respectively. Similarly, adult relatives had considerably higher
      mean tender point counts than controls: 4.0 vs 0.04 (p < 0.01) and 10.3 vs 0.28
      (p < 0.01) respectively, for males and females. CONCLUSION: Relatives of patients
      with FM have a higher prevalence of FM and are more tender than the general
      population, as recently reported and shown in a healthy control group. This
      finding can be attributed to genetic and environmental factors.

PMID- 9150087
TI  - Long-term health outcomes and quality of life in American and Italian inception
      cohorts of patients with juvenile rheumatoid arthritis. I. Outcome status.
AB  - OBJECTIVE: To assess the long-term health outcomes and quality of life of
      patients with juvenile rheumatoid arthritis (JRA) using health and functional
      assessment questionnaires in 2 populations, one from the USA and one from Italy.
      METHODS: Patient eligibility criteria: (1) first examined in our units between
      1958 and 1990 during the first 6 months after onset of symptoms, (2) diagnosis of
      JRA by the American College of Rheumatology criteria, (3) disease duration of at
      least 5 years at the time of assessment of outcome. Instruments used: (1) the
      Health Assessment Questionnaire (HAQ, short form, or childhood HAQ (CHAQ), and
      (2) Quality of Life Scales (QOLS, adults only). Eligible patients were identified
      by computer search and chart review and were then mailed a packet containing a
      consent/assent form and the assessment instruments. RESULTS: Of 346 patients who
      met the eligibility criteria were able to locate 301, and 290 verbally agreed to
      participate and were mailed packets. Signed consent and complete information were
      received from 227 of the 290 (78%), 178 from the USA and 49 from Italy. Mean
      duration of disease at the time of outcome assessment was 15 yrs. 127 had
      pauciarticular, 55 polyarticular, and 45 systemic onset disease. Mean and
      (median) scores of the outcomes are shown in the table. [table: see text]
      CONCLUSION: Long-term outcome, as assessed by the instruments used, is very
      favorable in most patients with JRA 5 years or more after onset of symptoms.

PMID- 9150088
TI  - Long-term health outcomes and quality of life in American and Italian inception
      cohorts of patients with juvenile rheumatoid arthritis. II. Early predictors of
      outcome.
AB  - OBJECTIVE: To determine whether demographic, clinical, and immunogenetic
      variables measurable during the first 6 months of illness long-term health
      outcomes and quality of life in patients with juvenile rheumatoid arthritis
      (JRA). METHODS: Patient eligibility criteria: (1) first examined in our units
      between 1958 and 1990 within 6 months of onset of symptoms; (2) diagnosis of JRA
      by American College of Rheumatology criteria; (3) disease duration of at least 5
      years at the time of assessment of outcome. Instruments used: (1) the Health
      Assessment Questionnaire (HAQ, short form), or Childhood HAQ (CHAQ) to measure
      disability (0-3 scale), (2) pain, and (3) parental assessment of overall well
      being, each scored on a 15 cm visual analog scale; (4) the Quality of Life Scales
      (QOLS) (adults only). Independent variables that showed significant results using
      univariate tests underwent multiple logistic regression analysis. RESULTS: 227
      patients were available for analysis. Mean duration of disease at time of
      assessment of outcome was 15 years (range 5.3-36.1). Univariate tests allowed 11
      variables for disability, 9 for pain, 7 for overall well being, and 4 for QOL
      into the multivariate analysis. The best predictor of higher disability was the
      articular severity score (odds ratio, OR, 5.69) while antinuclear antibody
      positivity foretold less disability (OR 0.29). HLA-DR5 positivity conferred the
      greatest risk for pain (OR 3.34), while HLA-B5, DR3, and C3 were protective (OR
      0.25, 0.28, 0.33, respectively). Early hand involvement was the strongest
      predictor of poorer overall well being (OR 8.75). Only the erythrocyte
      sedimentation rate was predictive of future QOL, but the model yielded a low C
      statistic (< 70%) and the OR 95% confidence limits were extreme (OR 9.77; 95%
      confidence interval, 1.22-77.8). CONCLUSION: Clinical and immunogenetic variables
      measurable within 6 months of onset of JRA can be used to predict future
      disability, pain, and well being. QOL appears more difficult to forecast, perhaps
      due to the multiple domains that make up this outcome. Further study is needed to
      identify other genetic and laboratory factors that predict outcome in JRA with
      greater precision.

PMID- 9150089
TI  - Immunity to cartilage link protein in patients with juvenile rheumatoid
      arthritis.
AB  - OBJECTIVE: To determine whether children with juvenile rheumatoid arthritis (JRA)
      express cellular immunity to cartilage link protein. METHODS: Link protein was
      purified from human fetal epiphyseal and bovine adult nasal cartilage. It was
      used in proliferation assays with the peripheral blood lymphocytes isolated from
      54 children with JRA and 22 nonarthritic controls. RESULTS: Patients with JRA
      expressed a significantly higher prevalence of cellular proliferation to human
      link protein compared with the control group, independent of whether they had
      pauciarticular, polyarticular, or systemic disease. In the case of bovine link
      protein, significant differences were only noted for the polyarticular group.
      There was significant correlation between the immunity to bovine and to human
      link proteins. Furthermore, immune responses to both molecules correlated with
      measures of joint disease activity. CONCLUSION: These results suggest that
      immunity to link protein may play a role in the pathogenesis of JRA.

PMID- 9150090
TI  - Cutaneous necrotizing vasculitis associated with hepatitis A virus infection.
AB  - Hepatitis A virus has been recognized as an etiologic factor of cutaneous
      necrotizing vasculitis in only 2 adult cases. We describe a 2-year-old Bedouin
      girl who developed cutaneous necrotizing vasculitis during the acute phase of
      hepatitis A infection. The cutaneous punch biopsy from an ecchymotic lesion
      revealed microscopic findings of a necrotizing vasculitis process involving the
      superficial and deep blood vessel plexuses. Fibrin thrombi were present in the
      lumen of a few blood vessels. She was treated with 2 mg/kg/day, tapered during 5
      weeks. Serum liver enzymes returned to the normal range within 6 weeks of the
      first presenting symptom. A few skin scars were noted in previously necrotic
      areas. Hepatitis A is one of many viruses that may be an etiologic factor in
      development of cutaneous necrotizing vasculitis in children.

PMID- 9150091
TI  - Postpartum lupus erythematosus associated with parvovirus B19 infection.
AB  - We describe postpartum onset of systemic lupus erythematosus (SLE) associated
      with parvovirus B19 infection in a mother presenting with fever, polyarthritis,
      erythema, and multiorgan involvement. B19 infection was revealed by detection of
      B19 DNA and IgM antibodies. In addition, our patient showed low CD4+ (384 x
      10(6)/l) and CD8+ (213 x 10(6)/l) T cells, high immunoglobulin values (23.77
      g/l), hypocomplementemia, thrombocytopenia, leukopenia, and anemia. Her daughter
      had rash associated with increasingly high B19 IgG levels and transient
      antinuclear and anti-ds-DNA antibodies, suggesting that both development of SLE
      and active B19 infection occurred in pregnancy and B19 was transmitted
      prenatally. A 2 year followup showed persisting polyarthritis in the mother and
      atopy in the daughter.

PMID- 9150092
TI  - Pustulotic arthro-osteitis associated with acetabular cartilage lesion in
      pustulotic arthropathy--implication of bone marrow.
AB  - We describe a case of pustulotic arthro-osteitis with hip joint involvement.
      After right hip joint and walking did not improve despite drugs and physical
      therapy, total hip replacement was performed. During surgery, brownish
      degenerated tissue was detected on the surface of the acetabular side.
      Pathohistological examination revealed that granulation tissue caused by
      suppurative inflammation of the bone marrow had broken through the cartilage
      surface, reaching the superficial layer. Our findings suggest that hip joint
      lesions in pustulotic arthro-osteitis may originate from bone marrow lesions.

PMID- 9150093
TI  - Remitting seronegative symmetrical synovitis with pitting edema associated with
      gastric carcinoma.
AB  - We report a case of remitting seronegative symmetrical synovitis with pitting
      edema (RS3PE syndrome) associated with gastric carcinoma in an 80-year-old woman
      who developed polyarthritis with marked pitting edema of the dorsa of both hands
      and feet 7 days after fiberscopic examination of the stomach. A mass lesion was
      identified and histology of the biopsy specimen revealed gastric carcinoma.
      Polyarthritis and edema were partially relieved by an intraarticular injection of
      corticosteroid. Shortly after resection of the gastric carcinoma, her symptoms
      and signs disappeared. She has been free of symptoms for 3 yrs without
      medication.

PMID- 9150094
TI  - Prepatellar bursitis: a unique presentation of tophaceous gout in an
      normouricemic patient.
AB  - We describe a patient with no history of gout and persistently normal serum uric
      acid concentrations in whom septic acute prepatellar bursitis was diagnosed
      initially, but empiric antibiotic therapy failed. Urate crystals were detected
      when the prepatellar bursa was aspirated for the 3rd time, and the diagnosis was
      changed to gouty bursitis. The case illustrates the importance of repeatedly
      aspirating suspicious sites to establish the diagnosis in elusive cases of
      crystal deposition disease.

PMID- 9150095
TI  - Psychosocial measures in musculoskeletal trials.
AB  - Measurement of psychological and social factors in studies of musculoskeletal
      disorders has become increasingly important with the need to show an effect of
      interventions on individuals' lives. Because information of psychological states
      involves patients reporting their private sensations, specific issues of their
      assessment need to be considered. Two of these issues are the problem of what
      constitutes the gold standard and the interpretation of causal direction of
      effects. The role of psychosocial factors in the assessment of disability is
      often ignored and frequently the distinction between disability and handicap
      confused. I describe and discuss the different measures commonly used to assess
      disability in arthritis. The assessment of symptoms, such as pain, stiffness, and
      fatigue are considered, as well as the examination of psychological well being.
      Interactions between these factors are also discussed. A number of other
      psychological variables have been developed and found to play a mediating role
      between the illness and its effect. These include coping, social support and
      other health cognitions, such as perceptions of control. The important role of
      psychosocial factors and their effect on measures on symptoms and disability
      suggest that need for more detailed examination of factors associated with
      outcome, and also the need to consider more complex designs that control for some
      of these factors at the outset of studies.

PMID- 9150096
TI  - The assessment of disability and handicap in musculoskeletal disease.
AB  - The method for assessment of disability and handicap is particularly important in
      chronic musculoskeletal diseases. Outcome measures should be valid and show a
      responsiveness to change such that longitudinal studies of the diseases and their
      interventions can be carried out effectively. Psychosocial aspects may
      significantly influence these diseases and the instruments themselves.
      Researchers need to take these issues into account.

PMID- 9150097
TI  - Practical issues in psychosocial measures.
AB  - Psychosocial variables were recognized as key clinical determinants and outcomes
      in rheumatic disease. Clinical interventions can produce clinically important
      improvement in psychological status, and clinicians regularly employ anxiolytic
      and antidepressant drugs. Yet assessment of psychological status is rarely
      undertaken in routine clinical practice. In part, this failure stems from the
      fact that most formal psychological instruments are too complicated, take too
      much time to administer, cannot be administered in real time, and are difficult
      to interpret. A practical way to assess psychological status in the clinic is to
      use short depression instruments such as the Center for Epidemiological Studies
      Depression scale (CES-D) or the Arthritis Impact Measurement Scales (AIMS)
      anxiety and depression subscales. Another approach to psychological assessment is
      to measure surrogate variables, that is, variables that are not primarily
      psychological and have practical use in rheumatic disease care. The Clinical
      Health Assessment Questionnaire (CLINHAQ) assesses such surrogate variables via
      visual analog scales for pain, fatigue, and sleep disturbance, the helplessness
      subscale of the Rheumatology Attitudes index, a self-report measure of
      satisfaction with health, and the AIMS anxiety and depression scales. This
      instrument, which also contains the Health Assessment Questionnaire disability
      index, a pain diagram, and assessment of global severity, can be completed in 5
      minutes by almost all clinic patients.

PMID- 9150098
TI  - Measures of physical function and emotional well being for young adults with
      arthritis.
AB  - We investigated whether it is necessary to adapt measures of functional status as
      used with adults with rheumatoid arthritis when measuring physical function in
      young adults between 16 and 30 years of age with arthritis, and which aspects of
      emotional well being are important outcomes in young adults with arthritis. A
      questionnaire as filled in by 196 young adults with arthritis and 117 healthy
      peers of same age and sex. Functional status was measured with the 17 item Young
      Adults Disability Inventory (YADI), which includes the 8 item Modified Health
      Assessment Questionnaire (M-HAQ). Four aspects of emotional well being were
      assessed: depression, anxiety, loneliness, and self-esteem. The mean score of the
      patients on the YADI was significantly higher than that on the M-HAQ. YADI scores
      correlated significantly higher with a measure of disease symptoms than the
      scores on the M-HAQ with disease symptoms. Anxiety was not strongly correlated
      with functional status, disease symptoms, or self-reported Thompson joint score.
      Depression, loneliness, and self-esteem were moderately correlated with
      functional status and disease symptoms and weakly correlated with the Thompson
      score. There were no significant difference in emotional well being between
      patients and their healthy peers. Patients with severe symptoms were
      significantly more depressed than their healthy peers. It seems that the YADI is
      more appropriate measure of functional status in young adults with arthritis than
      the M-HAQ. Depression seems to be an important emotional outcome for young adults
      with arthritis. Anxiety does not seem to be a severely affected area of emotional
      well being.

PMID- 9150099
TI  - Psychological aspects of systemic lupus erythematosus: cognitive function, mood,
      and self-report.
AB  - Systemic lupus erythematosus (SLE) is a chronic relapsing/remitting autoimmune
      disorder with both primary and secondary effects on nervous system integrity and
      psychological functioning. In addition to the occurrence of clinical psychiatric
      syndromes such as psychosis, depression, and anxiety, other psychological
      problems documented with increased frequency in SLE include cognitive deficits
      and emotional distress. We examine issues related to cognitive function,
      including its assessment and prevalence, and confounding factors in interpreting
      cognitive problems as reflecting primary central nervous system involvement in
      SLE. Cognitive data in relation to other facets of the disease such as pain and
      fatigue, and subjective cognitive complaints are also discussed. Finally, we
      propose a potential role for cognitive assessment in the identification of SLE
      related depression.

PMID- 9150100
TI  - Psychological measures: practical issues in observational studies and clinical
      monitoring.
AB  - Psychological measures are important because they can influence the expression of
      pain and physical function in patients with arthritis. A number of instruments
      are now available that measure psychological distress and how we as individuals
      manage stress. These instruments have undergone extensive validation, although
      more work is required to evaluate the performance of these instruments measuring
      change over time. One way to interpret psychological measures and to evaluate how
      they change over time is to use normative comparisons that are conditional on
      time and other relevant covariates, using statistical methods such as quantile
      regression. Such methods have been used to interpret the developmental,
      educational, and physical growth of children. We can use similar methods to
      interpret observational studies and to guide decisions within the context of
      clinical practice.

PMID- 9150101
TI  - Psychosocial measures.

PMID- 9150102
TI  - Zolpidem efficacy in fibromyalgia.

PMID- 9150103
TI  - Silicone breast implants and breast feeding.

PMID- 9150104
TI  - Silicone breast implants and breast feeding.

PMID- 9150105
TI  - Magnetic resonance imaging in fluoroquinolone induced tendinopathy.

PMID- 9150106
TI  - Correlation of erythrocyte sedimentation rate and outdoor temperature in a
      patient with rheumatoid arthritis.

PMID- 9150107
TI  - A case of amyloidosis due to multiple myeloma that resembled systemic sclerosis.

PMID- 9150108
TI  - Persian Gulf War myalgia syndrome.

PMID- 9150109
TI  - Atypical antineutrophil cytoplasmic antibodies sera do not react with MRP8/14
      neutrophil cytosolic proteins.

PMID- 9150110
TI  - The evolving role of blood and marrow transplantation for the treatment of
      autoimmune diseases.
AB  - With over 4 decades of seminal contributions to the development and application
      of BMT, Dr. Thomas stresses the importance of collaboration between
      rheumatologists and transplant clinicians in developing this evolving area of
      treatment. While the debate concerning the value of TBI in the conditioning
      regimen and the use of autologous or allogeneic stem cells will continue, he
      states there is simply no other way to answer these questions than to begin well
      designed clinical studies. As pointed out by Dr. Hahn, unexpected post-transplant
      complications may arise in patients with SSc and SLE and possibly require
      modifications to the transplant procedure similar to the experience in patients
      with other specific diseases. Other difficulties may be encountered, including
      restricted funding of the transplant procedure by insurance carriers. The
      emergence of managed care contracts and payer limitations in the United States
      described by Dr. Appelbaum could hinder the development of innovative, curative
      therapies. As initial clinical data are being collected, it is vital to actively
      support patient referral and participation in clinical studies that will
      ultimately establish the indications, risks, costs, and benefits of hematopoietic
      stem cell transplantation for autoimmune disease.

PMID- 9150111
TI  - Preclinical investigations that subserve efforts to employ bone marrow
      transplantation for rheumatoid or autoimmune diseases.
AB  - Bone marrow transplantation (BMT) results in the replacement of host
      immunohematopoiesis with that of the donor. This procedure may be appropriate for
      patients with severe combined immunodeficiency disease, Wiskott-Aldrich syndrome,
      and after lethal myeloablation for treatment of leukemia. Preclinical studies in
      experimental mice with autoimmune disorders indicate that BMT may successfully
      prevent the development or induce remission of disease. In some experimental
      models both marrow and stroma must be transplanted for a successful outcome.
      Allogeneic, rather than syngeneic, transplants are required for successful
      outcome in these genetically based spontaneous models of autoimmune disease.
      However, remissions of relapsing forms of demyelinating autoimmune (acquired)
      central nervous system diseases can be achieved with both syngeneic and
      allogeneic marrow transplantation. These preclinical studies form part of the
      rationale for considering BMT as treatment for severe autoimmune diseases.

PMID- 9150112
TI  - Stem cell transplantation for severe autoimmune disorders, with special reference
      to rheumatic diseases.
AB  - Animal models of autoimmune disease have been successfully used to explore
      peripheral stem cell transfusion and bone marrow transplantation. Allogeneic
      marrow transplants have been shown to suppress lupus-like disease and
      experimental allergic encephalomyelitis. Autologous transplantation has also been
      successful in adjuvant arthritis. Operationally, these may be considered as graft
      versus autoimmunity effects. In humans, adoptive autoimmunity, in which the donor
      becomes apparent in the recipient, has been documented for myasthenia gravis and
      insulin dependent diabetes mellitus. Of 9 allogeneic bone marrow transplants for
      rheumatoid arthritis, 4 patients have done well for many years while one relapsed
      after 2 years. In 2 cases, autologous marrow transplant has been used
      specifically to treat autoimmune disease: one patient with CREST had only a
      transient response and one patient with myasthenia gravis had remission. While
      allogeneic bone marrow transplant is the most rational procedure, its use in
      nonmalignant disorders must be very carefully considered secondary to its
      toxicity and potential morbidity. The use of peripheral blood CD34+ cells with T
      cell depletion, may promise complete or partial longterm remission but results of
      this therapy need to be compared with other immunosuppressive combinations.

PMID- 9150113
TI  - Hematopoietic stem cell transplantation for autoimmune diseases.
AB  - Autoimmune diseases such as systemic lupus erythematosus, scleroderma, and
      rheumatoid arthritis cause significant morbidity and mortality. Although
      aggressive treatments may suppress disease activity in some cases, there are few
      if any complete cures. Since these conditions arise as a direct result of
      dysregulation of the immune system, modification of immune stem cells may be
      important in their control. Some slow acting antirheumatic drugs have significant
      effect on bone marrow, and more recently a number of case reports have appeared
      in which autoimmune diseases have gone into remission after bone marrow
      transplantation for other reasons. Data from animal models of autoimmune disease
      show significant abrogation of inflammation following bone marrow
      transplantation. Advances in the technology of stem cell transplantation coupled
      with increasing ability to identify at an early stage those patients likely to
      develop severe autoimmune disease require an indepth study of the role of stem
      cell transplantation for these conditions.

PMID- 9150114
TI  - Pre-existing autoimmune disease in patients with long-term survival after
      allogeneic bone marrow transplantation.
AB  - We reviewed the experience with allogeneic bone marrow transplantation (BMT) at
      Fred Hutchinson Cancer Research Center and affiliated Seattle hospitals for
      patients with preexisting autoimmune diseases. The review was limited to patients
      who received transplants between 1969 and 1989 from a related donor and who had
      at least 3 years of relapse-free survival. Of 901 evaluable patients, 11 were
      identified with a preexisting autoimmune disease and 2 with diseases that were
      possibly autoimmune in nature. Pretransplant diseases identified in this review
      included rheumatoid arthritis (n = 1), discoid or systemic lupus (n = 2), insulin
      dependent Type 1 diabetes (n = 3), hyperthyroidism (n = 4), dermatitis
      herpetiformis (n = 1), vasculitis (n = 1), and Crohn's disease (n = 1). All 13
      patients survive with a median followup of 14 (range, 7-20) years after
      transplantation from an HLA identical sibling (n = 10), parent (n = 1) or
      identical twin (n = 2). Pre and post-transplant histories are presented.
      Variables to be considered in the assessment of any beneficial effect of BMT are
      discussed, including consideration of different patterns of activity that
      describe the natural history of various autoimmune diseases. Although autoimmune
      disease did not recur after allogeneic BMT in these 13 patients, disease and post
      transplant variables may confound the interpretation of results from
      retrospective analysis.

PMID- 9150115
TI  - Hematopoietic stem cell transplantation in nonmalignant diseases.
AB  - Treatment of patients with nonmalignant hematopoietic diseases by marrow grafts
      from HLA identical family members has progressed to a point where event free
      survivals of 75-90% can be expected. For allografts to be successful,
      conditioning programs have been devised that provide both the immunosuppression
      and the marrow space required for the incoming grafts to be accepted. Despite
      graft versus host disease prevention with methotrexate and cyclosporine, the
      acute and chronic forms of this disease continue to pose problems for a minority
      of patients after transplant, and they may necessitate prolonged courses of
      immunosuppressive therapy. The transplant procedures required for patients with
      these nonmalignant hematopoietic diseases could be directly applied to patients
      with autoimmune diseases.

PMID- 9150116
TI  - The use of autologous transplantation in the treatment of malignant disorders.
AB  - Autologous transplantation uses high dose chemotherapy (with or without radiation
      therapy) followed by hematopoietic stem cell support in an attempt to cure
      certain malignant conditions. Autotransplantation can be considered as a
      treatment modality, if the tumor demonstrates a steep dose-response curve, marrow
      toxicity is the major dose limiting side effect of the active chemotherapeutic
      agents, and the source of the cells used for hematopoietic reconstitution is free
      of viable tumor cells. Hematopoietic stem cells can be obtained from peripheral
      blood after recovery from chemotherapy induced neutropenia or following treatment
      with hematopoietic growth factors and these peripheral blood stem cells are the
      predominant product used for autologous transplants at the present time.
      Autotransplantation has been shown to be useful in the treatment of certain
      patients with lymphomas, leukemias, myeloma, breast cancer, testicular cancer,
      ovarian cancer, and selected other tumors.

PMID- 9150117
TI  - Allogeneic stem cell transplantation for the treatment of hematologic
      malignancies: current indications and challenges.
AB  - Allogeneic stem cell transplantation is a potentially curative treatment for
      hematologic malignancies. Research efforts are expanding the acceptable donor
      pool to increase patient access to this form of therapy. Potential sources
      besides HLA matched siblings include partially mismatched family members,
      unrelated volunteers, and cord blood stem cells. Although allogeneic
      hematopoietic stem cell (ASC) transplantation may cure hematologic malignancies,
      relapse remains a problem. To prevent relapse after transplant, research efforts
      are focused on optimizing the delivery of systemic chemoradiotherapy, including
      strategies for targeting therapy to sites of disease, and augmenting the
      antileukemic effect of the allogeneic graft. It is a challenge to maintain
      clinical research in the current environment of limited resources, so new
      paradigms for support of this work may need consideration.

PMID- 9150118
TI  - Longterm followup and quality of life after hematopoietic stem cell
      transplantation.
AB  - The success of marrow or blood stem cell transplantation may depend upon events
      arising months to years later. Transplant regimen related toxicity may include
      cataract formation due to corticosteroids or total body irradiation (TBI) and
      endocrine or gonadal dysfunction requiring hormonal replacement. By 15 to 20
      years post-transplant, the cumulative incidence of secondary malignancies
      (including skin cancers) ranges from 4% (no TBI) to 14% (prior irradiation) in
      patients with previous aplastic anemia. Chronic graft versus-host-disease (GVHD)
      develops in 33% of HLA-identical sibling transplants and requires 1 to 2 years of
      immunosuppressive therapy. In allograft recipients free of GVHD, there are very
      few late infections or complications. These findings are confirmed by
      multidimensional studies of the quality of life of adult patients surviving 6 to
      18 years after marrow transplantation and demonstrate that 80% of patients rate
      their quality of life as good to excellent and 5%, as poor. Considerations of
      late effects of transplant and maintenance of quality of life are key
      considerations when weighing the risks and benefits of stem cell grafts for the
      treatment of severe autoimmune diseases. Careful followup and reporting of these
      initial patient cohorts will be vital in determining the longterm success of stem
      cell transplantation.

PMID- 9150119
TI  - Hypothesis for the pathogenesis of systemic sclerosis.
AB  - An hypothesis for the pathogenesis of systemic sclerosis is introduced. It posits
      a genetic background with environmental stimuli that activate immune cells. The
      immune cells, in turn, may damage vascular endothelium, cause proliferation of
      fibroblasts, or stimulate fibroblasts to produce collagen. Endothelial cell
      damage can also activate the immune system or induce fibroblast proliferation.
      Associated with fibroblast proliferation may be immune activation or collagen
      production. Finally, collagen production and end organ damage can induce immune
      activation thus perpetuating the cycle. Raynaud's phenomenon, an early finding in
      systemic sclerosis can cause vascular damage, thus entering the cycle at a
      different point than other environmental stimuli. This hypothesis will
      undoubtedly require change as data emerge, but it presents a conceptual model for
      testing and modification.

PMID- 9150120
TI  - Scleroderma--demographics and survival.
AB  - Scleroderma is a rare disease with limited data on its occurrence. Published
      prevalence rates vary widely with contemporary studies based on hospital
      ascertained cases, reporting rates of 30-120/million population. The annual
      incidence of new cases is much lower with rates of 2-20/million/year. Rates are
      substantially higher in females with a peak onset in the fifth and sixth decade.
      The disease is associated with a substantially reduced survival with
      approximately 50% surviving 10 years. Again, there is wide variation among
      studies probably reflecting patient selection factors. Apart from an increased
      risk of death from scleroderma related causes, there is also an increased cancer
      mortality particularly of the lung.

PMID- 9150121
TI  - Systemic lupus erythematosus: immunopathogenesis and the card game analogy.
AB  - Systemic lupus erythematosis (SLE) is a multifactorial disease with both genetic
      and environmental etiology. The complexity of factors contributing to SLE are
      considered in an analogy with a card game. The hears suit represents sex
      hormones. SLE is a disease of marked female prevalence and abnormal estrogen
      metabolism has been described in women with SLE. The clubs suit considers
      complement and other genetic factors. Increased risk of SLE has been described in
      association with some HLA markers and the complement C4A0 null allele. Although
      convincing evidence has not yet emerged, other candidate genes of importance are
      T cell receptor genes and genes encoding B cell immunoglobulin receptors and
      antibodies. Recently, abnormalities of apoptosis and of expression of the
      protooncogene Bcl-2 have been investigated. Overall different genes have been
      shown to increase the risk of SLE, and/or to influence the development of
      particular antibodies, and particular subsets of disease. The diamonds suit
      considers antigens and antibodies in the etiopathogenesis of SLE. Numerous
      autoantibodies have been described that bind a variety of targets on the cell
      surface, within the cytoplasm, or in the nucleus. It is generally agreed that
      autoantibodies develop as a consequence of both generalized polyclonal activation
      and antigen drive. The final suit of spades considers infectious, environmental,
      and other agents such as drugs, as triggers in the development of SLE.

PMID- 9150122
TI  - Systemic lupus erythematosus: demographics, prognosis, and outcome.
AB  - Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder with an
      annual incidence of 50 to 70/million and a prevalence of 500/million population.
      The highest incidence is observed in women aged 20 to 40 years. The clinical
      manifestations of SLE are remarkably heterogeneous. Major organ system
      involvement may occur in the heart, lungs, kidneys, and central nervous system
      and is responsible for most of the mortality and morbidity caused by the disease.
      Complications of drug treatment, in particular corticosteroid side effects,
      contribute to longterm morbidity. The major causes of death are directly related
      to the disease and include acute vascular neurologic events, renal failure,
      cardiovascular or pulmonary involvement, infection, and coronary artery disease.

PMID- 9150123
TI  - Development of a protocol for allogeneic marrow transplantation for severe
      systemic sclerosis: paradigm for autoimmune disease.
AB  - Some types of severe autoimmune disease are associated with significant morbidity
      and a high mortality rate. Many of these cases occur in young adults who, even if
      they survive, become severely debilitated. Systemic sclerosis (SSc) is a paradigm
      for other severe autoimmune diseases in which patients with poor prognostic
      features can be identified early in the course of the disease. Allogeneic marrow
      transplantation may be effective for the control of autoimmune diseases like SSc
      because the preparative regimen will significantly suppress the host immune
      system and the antihost effects of the donor immune system in the engrafted
      marrow will help maintain the suppression of the host immune system. Considering
      the morbidity and poor prognosis associated with severe SSc and the favorable
      outcome now associated with allogeneic marrow transplantation from HLA identical
      siblings for other nonmalignant diseases, Phase I and II studies are warranted.
      These will evaluate the safety of allogeneic marrow transplantation and explore
      its role in the management and control of a severe autoimmune disease. We review
      issues important in the development of an allogeneic marrow transplant protocol
      for severe SSc, including patient selection, plan of treatment, prevention of
      graft versus host disease, supportive care, and evaluation after transplant.

PMID- 9150124
TI  - Autologous stem cell transplantation for autoimmune diseases: issues in protocol
      development.
AB  - For patients with autoimmune disease resistant to conventional therapy,
      aggressive strategies employing high dose chemoradiotherapy and autologous stem
      cell transplant appear to be warranted. Support for this approach comes from
      animal studies employing marrow transplantation, which have shown promising
      results. Likewise, longterm control of autoimmune disease has been demonstrated
      in some survivors of allogeneic transplants for malignancy who incidentally had
      preexisting autoimmune disease. Initial strategies for autografting will use
      intensive transplant regimens incorporating cyclophosphamide with or without
      total body irradiation. Peripheral blood stem cell grafts purified by CD34
      selection will be depleted of lymphocytes, and lead to rapid hematologic
      reconstitution after treatment. Close monitoring for disease responses, adverse
      effects of intensive immunosuppression, and longterm sequelae of high dose
      therapies will be required. Initial studies are best performed as close
      collaborations between rheumatologists and transplant specialists in appropriate
      research centers.

PMID- 9150125
TI  - Choosing appropriate patients with systemic sclerosis for treatment by autologous
      stem cell transplantation.
AB  - Systemic sclerosis (SSc) with diffuse cutaneous scleroderma and visceral organ
      involvement is associated with considerable morbidity and mortality almost from
      its inception. Since the risk of accrual and progression of skin and organ
      complications is greatest in the first few years of SSc, the best opportunity for
      significantly modifying the course of SSc (prolonging survival and/or preventing
      or lessening the progressivity of organ involvement) is probably limited to the
      first 3 to 4 years. Transplantation of autologous stem cells (ASCT), after immune
      ablation of the host, has the potential to modify the disease course. Even though
      the mortality risk of ASCT is low (< 2% mortality in the first year), the
      mortality risk of the disease being treated must justify that risk. We suggest
      that patients with diffuse Sc of short duration (< 3 years from the first non
      Raynaud sign/symptom) with evidence of at least mild involvement of heart, lung,
      or kidney, have sufficiently severe disease to warrant ASCT. In contrast, we
      suggest that patients with severe/end stage organ involvement have progressed to
      the point where ASCT will not be helpful in improving that degree of organ
      involvement.

PMID- 9150126
TI  - The potential role of autologous stem cell transplantation in patients with
      systemic lupus erythematosus.
AB  - Transfer of disease by bone marrow cells has been described in experimental
      models of systemic lupus erythematosus (SLE). In one experiment, marrow ablation
      followed by transfer of T depleted allogeneic marrow resulted in prolonged
      survival of animals with SLE. Some experimental studies suggest a rationale for
      autologous stem cell transplantation indicating this intervention might "reset
      the thermostat" so that normal immunoregulation can control disease, while others
      indicate it might not be beneficial. The pros and cons of offering patients with
      SLE autologous hematopoietic stem cell transplantation are considered. A profile
      of the patient with SLE who might be considered as a candidate for autologous
      stem cell transplantation can be constructed by evaluating causes of death and
      factors that increase mortality. This profile includes life threatening disease,
      inadequate response to aggressive immunosuppressive therapy, and adequate
      function of all major organs so that risks associated with stem cell
      transplantation can be minimized.

PMID- 9150128
TI  - Hematopoietic stem cell transplants for autoimmune disease: role of EULAR.
      European League Against Rheumatism.
AB  - Despite improved survival of patients with systemic autoimmune disease, severe
      disease can still be lethal. Autologous human stem cell transplantation is an
      exciting therapeutic option for patients with organ or life threatening disease.
      The initial open pilot study must be safety oriented. Data collection will be
      standardized and centralized. Efforts will be coordinated by a working party from
      the European League Against Rheumatism and the European group for Blood and
      Marrow Transplantation.

PMID- 9150127
TI  - Hematopoietic stem cell transplantation in rheumatic diseases other than systemic
      sclerosis and systemic lupus erythematosus.
AB  - Hematopoietic stem cells (HSC) are increasingly available as an alternative to
      whole marrow aspirate for bone marrow transplantation (BMT). They may be derived
      from an HLA matched individual (allogeneic) or from the patient (autologous).
      Allogeneic BMT is associated with a 15 to 35% mortality, largely due to graft
      versus host disease. Autologous HSC are used to rescue the patient after severe
      immunosuppression, and the transplant related mortality is 3 to 5%. The
      opportunity to ablate severe autoimmune disease with increased safety is
      particularly attractive for necrotizing vasculitides,
      polymyositis/dermatomyositis, primary Sjogren's syndrome, systemic juvenile
      arthritis, relapsing polychondritis, and Behcet's disease, where correct
      selection of cases would ensure an acceptable benefit/risk ratio. Rheumatoid
      arthritis (RA), psoriasis associated arthritis (PsA) and some non-rheumatic
      diseases such as inflammatory bowel disease (IBD), multiple sclerosis, and type 1
      diabetes mellitus may also be candidates, but careful selection of patients with
      a poor prognosis is necessary. There are allogeneic BMT data from patients with
      aplastic anemia or leukemia and concurrent RA, PsA, and IBD and also autologous
      HSC BMT data from animal models to support the concept of cure. Patient studies
      should proceed using recently published protocol guidelines and centralized data
      collection.

PMID- 9150129
TI  - Pros and cons of stem cell transplantation for autoimmune disease.
AB  - The data and discussion at this symposium have provided a most useful analysis of
      the autoimmune diseases and their potential for therapy by stem cell
      transplantation. These diseases are characterized by threat to life and
      particularly by chronic, painful and debilitating courses that warrant aggressive
      therapy. Selection of patients will be difficult because of the variable disease
      course and the necessity to choose patients who still have reversible disease.
      The safety of both autologous and allogeneic stem cell grafting has progressed to
      the point where, in many cases, the risks of the disease far outweigh those of
      transplantation. In my opinion the data presented at this symposium show that we
      should proceed cautiously with both autologous and allogeneic stem cell grafts.
      Purified stem cells, which have the advantage of being free of lymphocytes,
      should be used for the first series of autologous studies. These studies are
      attractive because of the low risk of transplant related complications but are
      less likely to be curative. Allogeneic grafts from perfectly matched donors have
      the advantage of providing a completely new immunological environment. For this
      reason, I believe that curative results are most probable after allogeneic stem
      cell engraftment. Emphasis should be on the identification of patients with HLA
      matched siblings. Initially, these studies will be carried out in patients with
      advanced disease, as was the case in the early days of transplantation for
      leukemia. In considering more aggressive treatment for autoimmune diseases it
      appears there are 3 possible approaches. First, and most conservative, is to
      store peripheral blood stem cells for possible future marrow rescue and then to
      give higher doses of immunosuppressive agents, especially in combination, to see
      whether there is an improvement over conventional doses. Second, for those who
      prefer a conservative approach to stem cell transplantation, is to give
      myeloablative and lymphoablative chemotherapy followed by purified (lymphocyte
      free) hematopoietic stem cells. Third, and most likely to be curative, is
      myeloablative and lymphoablative therapy followed by stem cells from an HLA
      matched family member with subsequent short methotrexate and cyclosporine
      treatment to control GVHD. As we have heard, there are differences of opinion
      about whether the preparative regimen should include irradiation. It should be
      pointed out that total body irradiation is the most effective way to destroy
      lymphoid cells throughout the body. Careful monitoring of accumulating clinical
      results will pilot future investigation.

PMID- 9150130
TI  - A versatile transcriptional effector of Wingless signaling.

PMID- 9150131
TI  - What's up and down with histone deacetylation and transcription?

PMID- 9150132
TI  - The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a
      membrane-bound transcription factor.

PMID- 9150133
TI  - Histone deacetylase activity is required for full transcriptional repression by
      mSin3A.
AB  - Members of the Mad family of bHLH-Zip proteins heterodimerize with Max to repress
      transcription in a sequence-specific manner. Transcriptional repression by
      Mad:Max heterodimers is mediated by ternary complex formation with either of the
      corepressors mSin3A or mSin3B. We report here that mSin3A is an in vivo component
      of large, heterogeneous multiprotein complexes and is tightly and specifically
      associated with at least seven polypeptides. Two of the mSin3A-associated
      proteins, p50 and p55, are highly related to the histone deacetylase HDAC1. The
      mSin3A immunocomplexes possess histone deacetylase activity that is sensitive to
      the specific deacetylase inhibitor trapoxin. mSin3A-targeted repression of a
      reporter gene is reduced by trapoxin treatment, suggesting that histone
      deacetylation mediates transcriptional repression through Mad-Max-mSin3A
      multimeric complexes.

PMID- 9150134
TI  - Histone deacetylases associated with the mSin3 corepressor mediate mad
      transcriptional repression.
AB  - Transcriptional repression by Mad-Max heterodimers requires interaction of Mad
      with the corepressors mSin3A/B. Sin3p, the S. cerevisiae homolog of mSin3,
      functions in the same pathway as Rpd3p, a protein related to two recently
      identified mammalian histone deacetylases, HDAC1 and HDAC2. Here, we demonstrate
      that mSin3A and HDAC1/2 are associated in vivo. HDAC2 binding requires a
      conserved region of mSin3A capable of mediating transcriptional repression. In
      addition, Mad1 forms a complex with mSin3 and HDAC2 that contains histone
      deacetylase activity. Trichostatin A, an inhibitor of histone deacetylases,
      abolishes Mad repression. We propose that Mad-Max functions by recruiting the
      mSin3-HDAC corepressor complex that deacetylates nucleosomal histones, producing
      alterations in chromatin structure that block transcription.

PMID- 9150135
TI  - Histone deacetylases and SAP18, a novel polypeptide, are components of a human
      Sin3 complex.
AB  - An important event in gene expression is the covalent modification of histone
      proteins. We have found that the mammalian transcriptional repressor Sin3 (mSin3)
      exists in a complex with histone deacetylases HDAC1 and HDAC2. Consistent with
      the observation that mSin3-mediated repression of transcription involves the
      modification of histone polypeptides, we found that the mSin3-containing complex
      includes polypeptides that tether the mSin3 complex to core histone proteins. In
      addition, two novel mSin3-associated polypeptides, SAP18 and SAP30, were
      identified. We isolated a cDNA encoding human SAP18 and found that SAP18 is a
      component of an mSin3-containing complex in vivo. Moreover, we demonstrate a
      direct interaction between SAP18 and mSin3. SAP18 represses transcription in vivo
      when tethered to the promoter, consistent with the ability of SAP18 to interact
      with mSin3.

PMID- 9150136
TI  - Repression by Ume6 involves recruitment of a complex containing Sin3 corepressor
      and Rpd3 histone deacetylase to target promoters.
AB  - Sin3 and Rpd3 negatively regulate a diverse set of yeast genes. A mouse Sin3
      related protein is a transcriptional corepressor, and a human Rpd3 homolog is a
      histone deacetylase. Here, we show that Sin3 and Rpd3 are specifically required
      for transcriptional repression by Ume6, a DNA-binding protein that regulates
      genes involved in meiosis. A short region of Ume6 is sufficient to repress
      transcription, and this repression domain mediates a two-hybrid and physical
      interaction with Sin3. Coimmunoprecipitation and two-hybrid experiments indicate
      that Sin3 and Rpd3 are associated in a complex distinct from TFIID and Pol II
      holoenzyme. Rpd3 is specifically required for repression by Sin3, and artificial
      recruitment of Rpd3 results in repression. These results suggest that repression
      by Ume6 involves recruitment of a Sin3-Rpd3 complex and targeted histone
      deacetylation.

PMID- 9150137
TI  - Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and
      histone deacetylase.
AB  - The transcriptional corepressors SMRT and N-CoR function as silencing mediators
      for retinoid and thyroid hormone receptors. Here we show that SMRT and N-CoR
      directly interact with mSin3A, a corepressor for the Mad-Max heterodimer and a
      homolog of the yeast global-transcriptional repressor Sin3p. In addition, we
      demonstrate that the recently characterized histone deacetylase 1 (HDAC1)
      interacts with Sin3A and SMRT to form a multisubunit repressor complex.
      Consistent with this model, we find that HDAC inhibitors synergize with retinoic
      acid to stimulate hormone-responsive genes and differentiation of myeloid
      leukemia (HL-60) cells. This work establishes a convergence of repression
      pathways for bHLH-Zip proteins and nuclear receptors and suggests this type of
      regulation may be more widely conserved than previously suspected.

PMID- 9150138
TI  - Redistribution of silencing proteins from telomeres to the nucleolus is
      associated with extension of life span in S. cerevisiae.
AB  - A prior genetic study indicated that activity of Sir silencing proteins at a
      hypothetical AGE locus is essential for long life span. In this model, the SIR4
      42 mutation would direct the Sir protein complex to the AGE locus, giving rise to
      a long life span. We show by indirect immunofluorescence that Sir3p and Sir4p are
      redirected to the nucleolus in the SIR4-42 mutant. Furthermore, this
      relocalization is dependent on both UTH4 a novel yeast gene that extends life
      span, and its homologue YGL023. Strikingly, the Sir complex is relocalized from
      telomeres to the nucleolus in old wild-type cells. We propose that the rDNA is
      the AGE locus and that nucleolar function is compromised in old yeast cells in a
      way that may be mitigated by targeting of Sir proteins to the nucleolus.

PMID- 9150139
TI  - The yeast La protein is required for the 3' endonucleolytic cleavage that matures
      tRNA precursors.
AB  - Although the La autoantigen binds to the 3' ends of all nascent polymerase III
      transcripts, its function in vivo has long been unclear. Although S. cerevisiae
      cells lacking the La protein homolog Lhp1p are viable, cells containing a
      mutation that disrupts the anticodon stem of tRNA(Ser)CGA require Lhp1p for
      growth. We demonstrate that for the wild-type pre-tRNA(Ser)CGA and other pre
      tRNAs, Lhp1p is required for the normal endonucleolytic removal of the 3' trailer
      sequence. In cells lacking Lhp1p, the 3' trailer is removed by exonuclease(s).
      Although maturation of the mutant pre-tRNA(Ser)CGA requires Lhp1p, introduction
      of a second mutation that restores base pairing eliminates the requirement. We
      propose that binding by Lhp1p stabilizes pre-tRNAs in conformations that allow
      the 3' endonucleolytic cleavage to occur.

PMID- 9150140
TI  - Cross-intron bridging interactions in the yeast commitment complex are conserved
      in mammals.
AB  - The commitment complex is the first defined step in the yeast (S. cerevisiae)
      splicing pathway. It contains U1 snRNP as well as Mud2p, which resembles human
      U2AF65. In a genetic screen, we identified the yeast gene MSL-5, which is a novel
      commitment complex component. Genetic and biochemical criteria indicate a direct
      interaction between Msl5p and both Mud2p and the U1 snRNP protein Prp40p. This
      defines a bridge between the two ends of the intron. Msl5p (renamed BBP for
      branchpoint bridging protein) has a mammalian ortholog, the splicing factor SF1.
      Our results show that SF1 interacts strongly with human U2AF65, and that SF1 is a
      bona fide E complex component. This implies that aspects of these novel cross
      intron protein-protein interactions are conserved between yeast and mammals.

PMID- 9150141
TI  - The transcriptional activity of NF-kappaB is regulated by the IkappaB-associated
      PKAc subunit through a cyclic AMP-independent mechanism.
AB  - Stimulation of cells with inducers of NF-kappaB such as LPS and IL-1 leads to the
      degradation of IkappaB-alpha and IkappaB-beta proteins and translocation of NF
      kappaB to the nucleus. We now demonstrate that, besides the physical partitioning
      of inactive NF-kappaB to the cytosol, the transcriptional activity of NF-kappaB
      is regulated through phosphorylation of NF-kappaB p65 by protein kinase A (PKA).
      The catalytic subunit of PKA (PKAc) is maintained in an inactive state through
      association with IkappaB-alpha or IkappaB-beta in an NF-kappaB-IkappaB-PKAc
      complex. Signals that cause the degradation of IkappaB result in activation of
      PKAc in a cAMP-independent manner and the subsequent phosphorylation of p65.
      Therefore, this pathway represents a novel mechanism for the cAMP-independent
      activation of PKA and the regulation of NF-kappaB activity.

PMID- 9150142
TI  - Defective transcription-coupled repair in Cockayne syndrome B mice is associated
      with skin cancer predisposition.
AB  - A mouse model for the nucleotide excision repair disorder Cockayne syndrome (CS)
      was generated by mimicking a truncation in the CSB(ERCC6) gene of a CS-B patient.
      CSB-deficient mice exhibit all of the CS repair characteristics: ultraviolet (UV)
      sensitivity, inactivation of transcription-coupled repair, unaffected global
      genome repair, and inability to resume RNA synthesis after UV exposure. Other CS
      features thought to involve the functioning of basal transcription/repair factor
      TFIIH, such as growth failure and neurologic dysfunction, are present in mild
      form. In contrast to the human syndrome, CSB-deficient mice show increased
      susceptibility to skin cancer. Our results demonstrate that transcription-coupled
      repair of UV-induced cyclobutane pyrimidine dimers contributes to the prevention
      of carcinogenesis in mice. Further, they suggest that the lack of cancer
      predisposition in CS patients is attributable to a global genome repair process
      that in humans is more effective than in rodents.

PMID- 9150143
TI  - A primitive enzyme for a primitive cell: the protease required for excystation of
      Giardia.
AB  - Protozoan parasites of the genus Giardia are one of the earliest lineages of
      eukaryotic cells. To initiate infection, trophozoites emerge from a cyst in the
      host. Excystation is blocked by specific cysteine protease inhibitors. Using a
      biotinylated inhibitor, the target protease was identified and its corresponding
      gene cloned. The protease was localized to vesicles that release their contents
      just prior to excystation. The Giardia protease is the earliest known branch of
      the cathepsin B family. Its phylogeny confirms that the cathepsin B lineage
      evolved in primitive eukaryotic cells, prior to the divergence of plant and
      animal kingdoms, and underscores the diversity of cellular functions that this
      enzyme family facilitates.

PMID- 9150144
TI  - The vesicle docking protein p115 binds GM130, a cis-Golgi matrix protein, in a
      mitotically regulated manner.
AB  - The docking of transport vesicles with their target membrane is thought to be
      mediated by p115. We show here that GM130, a cis-Golgi matrix protein, interacts
      specifically with p115 and so could provide a membrane docking site. Deletion
      analysis showed that the N-terminus binds to p115, whereas the C-terminus binds
      to Golgi membranes. Mitotic phosphorylation of GM130 or a peptide derived from
      the N-terminus prevented binding to p115. The peptide also inhibited the NSF- but
      not the p97-dependent reassembly of Golgi cisternae from mitotic fragments,
      unless it was mitotically phosphorylated. Together, these data provide a
      molecular explanation for the COPI-mediated fragmentation of the Golgi apparatus
      at the onset of mitosis.

PMID- 9150145
TI  - Role of phosphoinositide 3-OH kinase in cell transformation and control of the
      actin cytoskeleton by Ras.
AB  - The pathways by which mammalian Ras proteins induce cortical actin rearrangement
      and cause cellular transformation are investigated using partial loss of function
      mutants of Ras and activated and inhibitory forms of various postulated target
      enzymes for Ras. Efficient transformation by Ras requires activation of other
      direct effectors in addition to the MAP kinase kinase kinase Raf and is inhibited
      by inactivation of the PI 3-kinase pathway. Actin rearrangement correlates with
      the ability of Ras mutants to activate PI 3-kinase. Inhibition of PI 3-kinase
      activity blocks Ras induction of membrane ruffling, while activated PI 3-kinase
      is sufficient to induce membrane ruffling, acting through Rac. The ability of
      activated Ras to stimulate PI 3-kinase in addition to Raf is therefore important
      in Ras transformation of mammalian cells and essential in Ras-induced
      cytoskeletal reorganization.

PMID- 9150146
TI  - Alternative initiation of translation and time-specific phosphorylation yield
      multiple forms of the essential clock protein FREQUENCY.
AB  - The frequency (frq) gene encodes central components of the
      transcription/translation-based negative-feedback loop comprising the core of the
      Neurospora circadian oscillator; posttranscriptional regulation associated with
      FRQ is surprisingly complex. Alternative use of translation initiation sites
      gives rise to two forms of FRQ whose levels peak 4-6 hr following the peak of frq
      transcript. Each form of FRQ is progressively phosphorylated over the course of
      the day, thus providing a number of temporally distinct FRQ products. The
      kinetics of these regulatory processes suggest a view of the clock where
      relatively rapid events involving translational regulation in the synthesis of
      FRQ and negative feedback of FRQ on frq transcript levels are followed by slower
      posttranslational regulation, ultimately driving the turnover of FRQ and
      reactivation of the frq gene.

PMID- 9150147
TI  - Thermally regulated translational control of FRQ mediates aspects of temperature
      responses in the neurospora circadian clock.
AB  - Two forms of FRQ, a central component of the Neurospora circadian clock, arise
      through alternative in-frame initiation of translation. Either form alone
      suffices for a functional clock at some temperatures, but both are always
      necessary for robust rhythmicity. Temperature regulates the ratio of FRQ forms by
      favoring different initiation codons at different temperatures; when either
      initiation codon is eliminated, the temperature range permissive for rhythmicity
      is demonstrably reduced. This temperature-influenced choice of translation
      initiation site represents a novel adaptive mechanism that extends the
      physiological temperature range over which clocks function. Additionally, a
      temperature-dependent threshold level of FRQ is required to establish the
      feedback loop comprising the oscillator. These data may explain how temperature
      limits permissive for rhythmicity are established, thus providing a molecular
      understanding for a basic characteristic of circadian clocks.

PMID- 9150148
TI  - Population genetics of BRCA1 and BRCA2.

PMID- 9150149
TI  - BRCA1 sequence variations in 160 individuals referred to a breast/ovarian family
      cancer clinic. Institut Curie Breast Cancer Group.
AB  - An account of familial aggregation in breast/ovarian cancer has become possible
      with the identification of BRCA1 germ-line mutations. We evaluated, for 249
      individuals registered with the Institut Curie in Paris, the prior probability
      that an individual carried a mutation that predisposes to these diseases. We
      chose 160 women for BRCA1 analysis: 103 with a family history of breast cancer
      and 57 with a family history of breast-ovarian cancer. To detect small mutations,
      we generated and analyzed 35 overlapping genomic PCR products that cover the
      coding portion of the gene, by using denaturing gradient gel electrophoresis.
      Thirty-eight truncating mutations (32 frameshifts, 4 nonsense mutations, and 2
      splice variants) were observed in 15% of women with a family history of breast
      cancer only and in 40% of those with a history of breast-ovarian cancer. Twelve
      of 25 distinct truncating mutations identified were novel and unique. Most BRCA1
      mutations that had been reported more than five times in the Breast Cancer
      Information Core were present in our series. One mutation (5149del4) observed in
      two apparently unrelated families most likely originates from a common ancestor.
      The position of truncating mutations did not significantly affect the ratio of
      the risk of breast cancer to that of ovarian cancer. In addition, 15 DNA variants
      (14 missense mutations and 1 neutral mutation) were identified, 9 of which were
      novel. Indirect evidence suggests that seven of these mutations are deleterious.

PMID- 9150150
TI  - BRCA2 in American families with four or more cases of breast or ovarian cancer:
      recurrent and novel mutations, variable expression, penetrance, and the
      possibility of families whose cancer is not attributable to BRCA1 or BRCA2.
AB  - In order to evaluate the role of inherited BRCA2 mutations in American families-
      particularly the appearance in America of European founder mutations--the BRCA2
      coding sequence, 5' UTR, and 3' UTR were screened in 22 Caucasian American
      kindreds with four or more cases of breast or ovarian cancer. Six mutations were
      found that cause a premature-termination codon; four of them have been reported
      elsewhere, and two are novel. In the four families with previously seen
      mutations, the distinct lineages at high risk of cancer were of Dutch, German,
      Irish, and Ashkenazi Jewish ancestry; mutations in Europe reflect these
      ancestries. The families with novel mutations were Puerto Rican Hispanic (exon 9
      deletion 995delCAAAT) and Ashkenazi Jewish (exon 11 deletion 6425delTT). Among
      female BRCA2-mutation carriers, risks of breast cancer were 32% by age 50 years,
      67% by age 70 years, and 80% by age 90 years, yielding a lifetime risk similar to
      that for BRCA1 but an older distribution of ages at onset. BRCA2 families also
      included multiple cases of cancers of the male breast (six cases), ovary (three
      cases), fallopian tube (two cases), pancreas (three cases), bladder (two cases),
      and prostate (two cases). Among 17 Ashkenazi Jewish families with four or more
      breast or ovarian cancers, 9 families (including 3 with ovarian cancer and 1 with
      male breast cancer) carried none of the three ancient mutations in BRCA1 or
      BRCA2. To date, both BRCA2 and BRCA1 have been screened by SSCA, supplemented by
      the protein-truncation test, in 48 families with four or more breast or ovarian
      cancers. Mutations have been detected in BRCA1 in 33 families, in BRCA2 in 6
      families, and in neither gene in 9 families, suggesting both the probable cryptic
      nature of some mutations and the likelihood of at least one other BRCA gene.

PMID- 9150151
TI  - A high proportion of novel mutations in BRCA1 with strong founder effects among
      Dutch and Belgian hereditary breast and ovarian cancer families.
AB  - We have identified 79 mutations in BRCA1 in a set of 643 Dutch and 23 Belgian
      hereditary breast and ovarian cancer families collected either for research or
      for clinical diagnostic purposes. Twenty-eight distinct mutations have been
      observed, 18 of them not previously reported and 12 of them occurring more than
      once. Most conspicuously, a 2804delAA mutation has been found 19 times and has
      never been reported outside the Netherlands. A common haplotype spanning > or =
      375 kb could be identified for each of the nine examined recurrent mutations,
      indicating the presence of multiple BRCA1 founder mutations in the Dutch
      population. The 2804delAA mutation has been estimated to have originated
      approximately 32 generations ago. No specific breast or ovarian cancer phenotype
      could be assigned to any of the common mutations, and the ovarian cancer
      incidence among 18 families with the 2804delAA mutation was heterogeneous.

PMID- 9150152
TI  - A low proportion of BRCA2 mutations in Finnish breast cancer families.
AB  - One hundred breast cancer families were identified at the Helsinki University
      Central Hospital in Finland and were screened for germ-line mutations in the
      coding regions and splice boundaries of the BRCA2 gene. Eight families (8%) were
      found to carry five different mutations, all of which are predicted to
      prematurely truncate the protein product. These BRCA2 families have early-onset
      breast cancer (mean and median age = 49 years), with four of the eight families
      including ovarian cancer but with no families including male breast cancer. A
      wide spectrum of other cancers also is seen in these families. Three mutations
      were identified in more than one family, and haplotype analysis in the families
      suggested a common founder for each recurrent mutation. One recurrent mutation,
      999del5, previously has been noted as a common mutation in Iceland. The
      relationship between the Icelandic 999del5 mutation and the Finnish 999del5
      mutation was explored by comparison of families from both countries. A common
      haplotype covering a minimal region intragenic to the BRCA2 gene was shared
      between the Icelandic and the Finnish mutation carriers.

PMID- 9150153
TI  - Founder BRCA1 and BRCA2 mutations in Ashkenazi Jews in Israel: frequency and
      differential penetrance in ovarian cancer and in breast-ovarian cancer families.
AB  - Germ-line BRCA1 and BRCA2 mutations account for most of familial breast-ovarian
      cancer. In Ashkenazi Jews, there is a high population frequency (approximately
      2%) of three founder mutations: BRCA1 185delAG, BRCA1 5382insC, and BRCA2
      6174delT. This study examined the frequency of these mutations in a series of
      Ashkenazi women with ovarian cancer unselected for family history, compared with
      the frequency of these mutations in families ascertained on the basis of family
      history of at least two affected women. Penetrance was compared, both according
      to the method of family ascertainment (i.e., on the basis of an unselected
      ovarian cancer proband vs. on the basis of family history) and for the BRCA1
      founder mutations compared with the BRCA2 6174delT mutation. There was a high
      frequency (10/22; [45%]) of germ-line mutations in Ashkenazi women with ovarian
      cancer, even in those with minimal or no family history (7/18 [39%]). In high
      risk Ashkenazi families, a founder mutation was found in 59% (25/42). Families
      with any case of ovarian cancer were significantly more likely to segregate a
      founder mutation than were families with site-specific breast cancer. Penetrance
      was higher in families ascertained on the basis of family history than in
      families ascertained on the basis of an unselected proband, but this difference
      was not significant. Penetrance of BRCA1 185delAG and BRCA1 5382insC was
      significantly higher than penetrance of BRCA2 6174delT (hazard ratio 2.1 [95% CI
      1.2-3.8]; two-tailed P = .01). Thus, the high rate of germ-line BRCA1/BRCA2
      mutations in Ashkenazi women and families with ovarian cancer is coupled with
      penetrance that is lower than previously estimated. This has been shown
      specifically for the BRCA2 6174delT mutation, but, because of ascertainment bias,
      it also may be true for BRCA1 mutations.

PMID- 9150154
TI  - Moderate frequency of BRCA1 and BRCA2 germ-line mutations in Scandinavian
      familial breast cancer.
AB  - Previous studies of high-risk breast cancer families have proposed that two major
      breast cancer-susceptibility genes, BRCA1 and BRCA2, may account for at least two
      thirds of all hereditary breast cancer. We have screened index cases from 106
      Scandinavian (mainly southern Swedish) breast cancer and breast-ovarian cancer
      families for germ-line mutations in all coding exons of the BRCA1 and BRCA2
      genes, using the protein-truncation test, SSCP analysis, or direct sequencing. A
      total of 24 families exhibited 11 different BRCA1 mutations, whereas 11 different
      BRCA2 mutations were detected in 12 families, of which 3 contained cases of male
      breast cancer. One BRCA2 mutation, 4486delG, was found in two families of the
      present study and, in a separate study, also in breast tumors from three
      unrelated males with unknown family history, suggesting that at least one BRCA2
      founder mutation exists in the Scandinavian population. We report 1 novel BRCA1
      mutation, eight additional cases of 4 BRCA1 mutations described elsewhere, and 11
      novel BRCA2 mutations (9 frameshift deletions and 2 nonsense mutations), of which
      all are predicted to cause premature truncation of the translated products. The
      relatively low frequency of BRCA1 and BRCA2 mutations in the present study could
      be explained by insufficient screening sensitivity to the location of mutations
      in uncharacterized regulatory regions, the analysis of phenocopies, or, most
      likely, within predisposed families, additional uncharacterized BRCA genes.

PMID- 9150155
TI  - Study of a single BRCA2 mutation with high carrier frequency in a small
      population.
AB  - Germ-line changes in the cancer-predisposition gene BRCA2 are found in a small
      proportion of breast cancers. Mutations in the BRCA2 gene have been studied
      mainly in families with high risk of breast cancer in females, and male breast
      cancer also has been associated with BRCA2 mutations. The importance of germ-line
      BRCA2 mutations in individuals without a family history of breast cancer is
      unknown. The same BRCA2 mutation has been found in 16/21 Icelandic breast cancer
      families, indicating a founder effect. We determined the frequency of this
      mutation, 999del5, in 1,182 Icelanders, comprising 520 randomly selected
      individuals from the population and a series of 632 female breast cancer patients
      (61.4% of patients diagnosed during the study period) and all male breast cancer
      patients diagnosed during the past 40 years. We detected the 999del5 germ-line
      mutation in 0.6% of the population, in 7.7% of female breast cancer patients, and
      in 40% of males with breast cancer. The mutation was strongly associated with
      onset of female breast cancer at age <50 years, but its penetrance and expression
      are varied. A number of cancers other than breast cancer were found to be
      increased in relatives of mutation carriers, including those with prostate and
      pancreatic cancer. Furthermore, germ-line BRCA2 mutation can be present without a
      strong family history of breast cancer. Comparison of the age at onset for
      mother/daughter pairs with the 999del5 mutation and breast cancer indicates that
      age at onset is decreasing in the younger generation. Increase in breast cancer
      incidence and lower age at onset suggest a possible contributing environmental
      factor.

PMID- 9150156
TI  - Screening for 185delAG in the Ashkenazim.
AB  - A study was initiated to assess interest, educational effectiveness, and
      implications of genetic testing for the common BRCA1 mutation, 185delAG, in the
      Ashkenazim. Of 333 individuals who attended group sessions, 309 (92%)
      participated in the study. Participants were categorized as having negative
      family history (67%), positive family history (defined, by a relaxed criterion,
      as one first-degree relative or two second-degree relatives with breast
      [premenopausal] or ovarian cancer) (22%), positive personal history (7%), and
      both positive personal history and positive family history (4%). Group education
      was effective, as shown by the improvement in participant scores from pre- to
      posteducation tests. For the 289 individuals (94%) who requested testing, the
      major reasons included concern for their own risk, concern for the risk of their
      children, and desire to learn about surveillance options. The most common reason
      given by participants who declined testing was concern about health insurance.
      Six participants found to be heterozygous for the 185delAG mutation received
      results and were offered genetic counseling. Participants had consented for
      additional testing without receiving results and were screened for the 6174delT
      mutation in BRCA2, and seven were found to be positive. All identified carriers
      reported at least one first- or second-degree relative with a history of breast
      or ovarian cancer, although they did not all meet our study criteria for positive
      family history. Given these outcomes, we conclude that screening for breast and
      ovarian cancer susceptibility is most appropriate for individuals with a positive
      personal or positive family cancer history. We propose a guideline for future
      studies designed to identify individuals who may benefit from genetic testing for
      inherited breast and ovarian cancer.

PMID- 9150157
TI  - Novel mutations and DNA-based screening in non-Jewish carriers of Tay-Sachs
      disease.
AB  - We have evaluated the feasibility of using PCR-based mutation screening for non
      Jewish enzyme-defined carriers identified through Tay-Sachs disease-prevention
      programs. Although Tay-Sachs mutations are rare in the general population, non
      Jewish individuals may be screened as spouses of Jewish carriers or as relatives
      of probands. In order to define a panel of alleles that might account for the
      majority of mutations in non-Jewish carriers, we investigated 26 independent
      alleles from 20 obligate carriers and 3 affected individuals. Eighteen alleles
      were represented by 12 previously identified mutations, 7 that were newly
      identified, and 1 that remains unidentified. We then investigated 46 enzyme
      defined carrier alleles: 19 were pseudodeficiency alleles, and five mutations
      accounted for 15 other alleles. An eighth new mutation was detected among enzyme
      defined carriers. Eleven alleles remain unidentified, despite the testing for 23
      alleles. Some may represent false positives for the enzyme test. Our results
      indicate that predominant mutations, other than the two pseudodeficiency alleles
      (739C-->T and 745C-->T) and one disease allele (IVS9+1G-->A), do not occur in the
      general population. This suggests that it is not possible to define a collection
      of mutations that could identify an overwhelming majority of the alleles in non
      Jews who may require Tay-Sachs carrier screening. We conclude that determination
      of carrier status by DNA analysis alone is inefficient because of the large
      proportion of rare alleles. Notwithstanding the possibility of false positives
      inherent to enzyme screening, this method remains an essential component of
      carrier screening in non-Jews. DNA screening can be best used as an adjunct to
      enzyme testing to exclude known HEXA pseudodeficiency alleles, the IVS9+1G-->A
      disease allele, and other mutations relevant to the subject's genetic heritage.

PMID- 9150158
TI  - Haplotype and phylogenetic analyses suggest that one European-specific mtDNA
      background plays a role in the expression of Leber hereditary optic neuropathy by
      increasing the penetrance of the primary mutations 11778 and 14484.
AB  - mtDNAs from 37 Italian subjects affected by Leber hereditary optic neuropathy
      (LHON) (28 were 11778 positive, 7 were 3460 positive, and 2 were 14484 positive)
      and from 99 Italian controls were screened for most of the mutations that
      currently are associated with LHON. High-resolution restriction-endonuclease
      analysis also was performed on all subjects, in order to define the phylogenetic
      relationships between the mtDNA haplotypes and the LHON mutations observed in
      patients and in controls. This analysis shows that the putative
      secondary/intermediate LHON mutations 4216, 4917, 13708, 15257, and 15812 are
      ancient polymorphisms, are associated in specific combinations, and define two
      common Caucasoid-specific haplotype groupings (haplogroups J and T). On the
      contrary, the same analysis shows that the primary mutations 11778, 3460, and
      14484 are recent and are due to multiple mutational events. However, phylogenetic
      analysis also reveals a different evolutionary pattern for the three primary
      mutations. The 3460 mutations are distributed randomly along the phylogenetic
      trees, without any preferential association with the nine haplogroups (H, I, J,
      K, T, U, V, W, and X) that characterize European populations, whereas the 11778
      and 14484 mutations show a strong preferential association with haplogroup J.
      This finding suggests that one ancient combination of haplogroup J-specific
      mutations increases both the penetrance of the two primary mutations 11778 and
      14484 and the risk of disease expression.

PMID- 9150159
TI  - Identification of common cystic fibrosis mutations in African-Americans with
      cystic fibrosis increases the detection rate to 75%.
AB  - Cystic fibrosis (CF)--an autosomal recessive disorder caused by mutations in CF
      transmembrane conductance regulator (CFTR) and characterized by abnormal chloride
      conduction across epithelial membranes, leading to chronic lung and exocrine
      pancreatic disease--is less common in African-Americans than in Caucasians. No
      large-scale studies of mutation identification and screening in African-American
      CF patients have been reported, to date. In this study, the entire coding and
      flanking intronic sequence of the CFTR gene was analyzed by denaturing gradient
      gel electrophoresis and sequencing in an index group of 82 African-American CF
      chromosomes to identify mutations. One novel mutation, 3120+1G-->A, occurred with
      a frequency of 12.3% and was also detected in a native African patient. To
      establish frequencies, an additional group of 66 African-American CF chromosomes
      were screened for mutations identified in two or more African-American patients.
      Screening for 16 "common Caucasian" mutations identified 52% of CF alleles in
      African-Americans, while screening for 8 "common African" mutations accounted for
      an additional 23%. The combined detection rate of 75% was comparable to the
      sensitivity of mutation analysis in Caucasian CF patients. These results indicate
      that African-Americans have their own set of "common" CF mutations that originate
      from the native African population. Inclusion of these "common" mutations
      substantially improves CF mutation detection rates in African-Americans.

PMID- 9150160
TI  - Multiple independent molecular etiology for limb-girdle muscular dystrophy type
      2A patients from various geographical origins.
AB  - Limb-girdle muscular dystrophies (LGMDs) are a group of neuromuscular diseases
      presenting great clinical heterogeneity. Mutations in CANP3, the gene encoding
      muscle-specific calpain, were used to identify this gene as the genetic site
      responsible for autosomal recessive LGMD type 2A (LGMD2A; MIM 253600). Analyses
      of the segregation of markers flanking the LGMD2A locus and a search for CANP3
      mutations were performed for 21 LGMD2 pedigrees from various origins. In addition
      to the 16 mutations described previously, we report 19 novel mutations. These
      data indicate that muscular dystrophy caused by mutations in CANP3 are found in
      patients from all countries examined so far and further support the wide
      heterogeneity of molecular defects in this rare disease.

PMID- 9150161
TI  - Linkage disequilibrium and physical mapping of X-linked juvenile retinoschisis.
AB  - X-linked juvenile retinoschisis (RS) is a recessively inherited disorder
      resulting in poor visual acuity. Affected males typically show retinal
      degeneration and intraretinal splitting. The prevalence of RS is 1:15,000
      1:30,000. Elsewhere we have mapped the RS gene between the markers DXS43 and
      DXS274 in Xp22.1-p22.2. To narrow the RS region, we analyzed 31 Finnish RS
      families with the markers DXS418, DXS999, DXS7161, and DXS365 and a new
      polymorphic microsatellite marker, HYAT1. Multipoint linkage analysis allowed us
      to localize the RS gene between the markers DXS418 and DXS7161 (LOD score =
      31.3). We have covered this region with nine YAC clones. On the basis of the
      sizes of the YACs, sequence-tagged site (STS) content mapping, and restriction
      mapping, the physical distance between DXS418 and DXS7161 is approximately 0.9
      Mb. A total of five potential CpG islands could be identified. For haplotype
      analysis, eight additional Finnish RS families were analyzed with the markers
      DXS1195, DXS418, HYAT1, DXS999, DXS7161, and DXS365. On the basis of the linkage
      disequilibrium data that were derived from the genetically isolated Finnish
      population, the critical region for RS could be narrowed to 0.2-0.3 cM, between
      the markers DXS418 and HYAT1.

PMID- 9150162
TI  - A gene for isolated congenital ptosis maps to a 3-cM region within 1p32-p34.1.
AB  - Hereditary isolated congenital ptosis is an autosomal dominant disorder with
      incomplete penetrance characterized by a variable degree of unilateral or
      bilateral drooping of the upper eyelids. We report linkage of this disorder in a
      large family to markers on chromosome 1p. In our sample of 37 meioses, nine
      informative markers did not recombine with the disease. D1S2677 gave a maximum
      two-point LOD score of 8.8 on the assumption of 90% penetrance (theta = 0).
      D1S447/2733 and D1S1616 flank the disease locus, with two-point LOD scores of
      5.6/6.6 (theta = .04) and 4.9 (theta = .05), respectively, defining a region of
      2.8 cM. FISH of YACs containing flanking recombinant markers localizes the gene
      to chromosome 1p32-p34.1. These data establish a map location for an isolated
      congenital ptosis gene and demonstrate that this disorder is genetically distinct
      from other extraocular muscle-specific disorders such as congenital fibrosis of
      the extraocular muscles and blepharophimosis.

PMID- 9150163
TI  - A genomewide linkage study of preeclampsia/eclampsia reveals evidence for a
      candidate region on 4q.
AB  - Preeclampsia (PE) and eclampsia (E) are potentially life-threatening conditions
      that can occur during human pregnancy. Generally considered to be different
      degrees of severity of the same disease process, the PE/E syndrome is thought to
      be predominantly genetic in origin, although its exact etiology and genetics are
      not fully understood. Here we report results of a genomewide linkage search for
      the gene(s) responsible for susceptibility to PE/E, using 15 informative
      pedigrees and 90 polymorphic DNA markers from all autosomes. Because of
      uncertainties concerning inheritance and diagnosis, four different models that
      assume maternal gene expression have been used to carry out LOD-score analysis.
      The region between D4S450 and D4S610 (2.8 cM) on the long arm of chromosome 4 was
      identified as a strong candidate region for a PE/E-susceptibility locus. The
      maximum multipoint LOD score within this interval was 2.9. Analysis of markers in
      the region around D4S450 and D4S610 by the affected-pedigree-member method also
      supported the possibility of a susceptibility locus in this region. However, to
      verify or exclude definitively linkage to this region, other groups of PE/E
      pedigrees will be required.

PMID- 9150164
TI  - A gene for autosomal dominant nonsyndromic hearing loss (DFNA12) maps to
      chromosome 11q22-24.
AB  - We performed linkage analysis in a Belgian family with autosomal dominant
      midfrequency hearing loss, which has a prelingual onset and a nonprogressive
      course in most patients. We found LOD scores >6 with markers on chromosome 11q.
      Analysis of key recombinants maps this deafness gene (DFNA12) to a 36-cM interval
      on chromosome 11q22-24, between markers D11S4120 and D11S912. The critical
      regions for the recessive deafness locus DFNB2 and the dominant locus DFNA11,
      which were previously localized to the long arm of chromosome 11, do not overlap
      with the candidate interval of DFNA12.

PMID- 9150165
TI  - Genetic relationships of Asians and Northern Europeans, revealed by Y-chromosomal
      DNA analysis.
AB  - We have identified a new T-->C transition on the human Y chromosome. C-allele
      chromosomes have been found only in a subset of the populations from Asia and
      northern Europe and reach their highest frequencies in Yakut, Buryats, and Finns.
      Examination of the microsatellite haplotypes of the C-allele chromosomes suggests
      that the mutation occurred recently in Asia. The Y chromosome thus provides both
      information about population relationships in Asia and evidence for a substantial
      paternal genetic contribution of Asians to northern European populations such as
      the Finns.

PMID- 9150166
TI  - Molecular analysis of deletion (17)(p11.2p11.2) in a family segregating a 17p
      paracentric inversion: implications for carriers of paracentric inversions.
AB  - A male child with multiple congenital anomalies initially was clinically
      diagnosed as having Smith-Lemli-Opitz syndrome (SLOS). Subsequent cytogenetic
      studies revealed an interstitial deletion of 17p11.2, which is associated with
      Smith-Magenis syndrome (SMS). Biochemical studies were not supportive of a
      diagnosis of SLOS, and the child did not display the typical SMS phenotype. The
      father's karyotype showed a paracentric inversion of 17p, with breakpoints in
      p11.2 and p13.3, and the same inversion was also found in two of the father's
      sisters. FISH analyses of the deleted and inverted 17p chromosomes indicated that
      the deletion was similar to that typically seen in SMS patients and was found to
      bracket the proximal inversion breakpoint. Available family members were
      genotyped at 33 polymorphic DNA loci in 17p. These studies determined that the
      deletion was of paternal origin and that the inversion was of grandpaternal
      origin. Haplotype analysis demonstrated that the 17p11.2 deletion arose following
      a recombination event involving the father's normal and inverted chromosome 17
      homologues. A mechanism is proposed to explain the simultaneous deletion and
      apparent "reinversion" of the recombinant paternal chromosome. These findings
      have implications for prenatal counseling of carriers of paracentric inversions,
      who typically are considered to bear minimal reproductive risk.

PMID- 9150167
TI  - The DiGeorge syndrome minimal critical region contains a goosecoid-like (GSCL)
      homeobox gene that is expressed early in human development.
AB  - The majority of patients with DiGeorge syndrome (DGS) and velocardiofacial
      syndrome (VCFS) have deletions of chromosomal region 22q11.2. The abnormalities
      observed in these patients include conotruncal cardiac defects, thymic hypoplasia
      or aplasia, hypocalcemia, and characteristic facial features. To understand the
      genetic basis of these disorders, we have characterized genes within the region
      that is most consistently deleted in patients with DGS/VCFS, the minimal DiGeorge
      critical region (MDGCR). In this report, we present the identification and
      characterization of a novel gene, GSCL, in the MDGCR, with homology to the
      homeodomain family of transcription factors. Further, we provide evidence that
      this gene is expressed in a limited number of adult tissues as well as in early
      human development. The identification of GSCL required a genomic sequence-based
      approach because of its restricted expression and high GC content. The early
      expression, together with the known role of homeobox-containing proteins in
      development, make GSCL an outstanding candidate for some of the abnormalities
      seen in DGS/VCFS.

PMID- 9150168
TI  - The likelihood of being affected with Huntington disease by a particular age, for
      a specific CAG size.
AB  - Prior studies describing the relationship between CAG size and the age at onset
      of Huntington disease (HD) have focused on affected persons. To further define
      the relationship between CAG repeat size and age at onset of HD, we now have
      analyzed a large cohort of affected and asymptomatic at-risk persons with CAG
      expansion. This cohort numbered 1,049 persons, including 321 at-risk and 728
      affected individuals with a CAG size of 29-121 repeats. Kaplan-Meier analysis has
      provided curves for determining the likelihood of onset at a given age, for each
      CAG repeat length in the 39-50 range. The curves were significantly different (P
      < .0005), with relatively narrow 95% confidence intervals (95% CI) (+/-10%).
      Penetrance of the mutation for HD also was examined. Although complete penetrance
      of HD was observed for CAG sizes of > or = 42, only a proportion of those with a
      CAG repeat length of 36-41 showed signs or symptoms of HD within a normal life
      span. These data provide information concerning the likelihood of being affected,
      by a specific age, with a particular CAG size, and they may be useful in
      predictive-testing programs and for the design of clinical trials for persons at
      increased risk for HD.

PMID- 9150169
TI  - Cost-effective sib-pair designs in the mapping of quantitative-trait loci.
AB  - The extreme discordant-sib-pair design has been found to be the most powerful,
      across most genetic models. In this paper, we address two of the most frequently
      asked questions related to this design. First, under the extreme discordant-sib
      pair design, a large number of people have to be screened for the phenotype of
      interest, before the desired number of discordant sibs can be collected for
      genotyping and linkage analysis. When the phenotyping cost is not negligible
      compared with the genotyping cost, such methods might not be cost effective. The
      second question is how sensitive the cost is to the genetic model and allele
      frequency. In this paper, we compare the cost under different sampling
      strategies, different genetic models, and different phenotyping:genotyping cost
      ratios. Because our knowledge of the underlying genetic model for a trait is
      limited, the discordant-sib-pair design proves to be the most robust. When the
      cost for screening probands is not included, the design that genotypes sibs with
      one sib in the top 10% and the other sib in the bottom 30% of the population with
      respect to the trait of interest is, across most models studied, the optimum
      among the designs considered in this paper. The cost under this design, across
      different genetic models, appears to be relatively robust to allele frequency and
      model type, whether additive or dominant. If probands initially must be screened
      as well, then 25% appears to be the optimal portions of the upper and lower
      distributions to be studied.

PMID- 9150170
TI  - Optimal strategies for mapping complex diseases in the presence of multiple loci.
AB  - Recent advances in genome technology have led to mapping and subsequent
      isolation, by positional cloning, of a number of genes for common and/or complex
      human diseases. It therefore will be possible to utilize information about a
      known locus in the search for additional, perhaps less penetrant, genes for a
      particular disease. It is also unclear, under these situations, what the optimal
      sampling strategy should be. To address these questions, we have calculated the
      expected LOD score for localizing one locus in a variety of two-locus models of
      disease, for four different pedigree structures, and under three different
      scenarios regarding knowledge/testing of one of the two loci. These design
      considerations are evaluated by use of a cost function that incorporates the
      costs of ascertaining different family structures, the relative costs of
      genotyping and mutation testing family members, and the amount of information
      provided by each family structure and testing scenario. The results indicate
      that, in most cases, affected sib pairs are a particularly poor strategy,
      especially when linkage or mutation data are available at the known locus. We
      also demonstrate that prescreening the sample of families for mutations at known
      susceptibility loci is, in general, a cost-effective strategy.

PMID- 9150171
TI  - Recurrent germ-line BRCA1 mutations in extended African American families with
      early-onset breast cancer.

PMID- 9150172
TI  - BRCA2 mutations in hereditary breast and ovarian cancer in France.

PMID- 9150173
TI  - Frequently occurring germ-line mutations of the BRCA1 gene in ovarian cancer
      families from Russia.

PMID- 9150174
TI  - Analysis of BRCA1 and BRCA2 mutations in Hungarian families with breast or breast
      ovarian cancer.

PMID- 9150175
TI  - Noncomplementation of radiation-induced chromosome aberrations in ataxia
      telangiectasia/ataxia-telangiectasia-variant heterodikaryons.

PMID- 9150176
TI  - Atypical Friedreich ataxia caused by compound heterozygosity for a novel missense
      mutation and the GAA triplet-repeat expansion.

PMID- 9150177
TI  - Anticipation in pediatric malignancies.

PMID- 9150178
TI  - Retinoic acid receptor expression abnormalities in lung cancer: important clues
      or major obstacles?

PMID- 9150180
TI  - An unlikely link? Researchers probe viral role in breast cancer.

PMID- 9150179
TI  - Time for integration of predictive factors for selection of breast cancer
      patients who need postoperative radiation therapy?

PMID- 9150181
TI  - Stereotactic surgery boosts accuracy when treating "hidden" brain tumors.

PMID- 9150182
TI  - ERT for survivors of endometrial cancer? A new trial will resolve debate.

PMID- 9150183
TI  - National Cancer Policy Board hears pleas for priority at first public forum.

PMID- 9150184
TI  - NCI Survivorship Office champions patient issues.

PMID- 9150185
TI  - Telomerase and early detection of cancer: a National Cancer Institute workshop.

PMID- 9150186
TI  - Suppression of retinoic acid receptor beta in non-small-cell lung cancer in vivo:
      implications for lung cancer development.
AB  - BACKGROUND: Retinoids, analogues of vitamin A, are required for the normal growth
      and differentiation of human bronchial epithelium. They are also able to reverse
      premalignant lesions and prevent second primary tumors in some patients with non
      small-cell lung cancer (NSCLC). These effects are thought to result from
      modulation of cell growth, differentiation, or apoptosis (programmed cell death).
      When certain retinoid receptors in the cell nucleus (i.e., retinoic acid
      receptors [RARs] and retinoid X receptors [RXRs]), which mediate most retinoid
      actions, are suppressed, abnormal activity may result that could enhance cancer
      development. PURPOSE: This study was designed to determine whether there are
      abnormalities in the expression of retinoid receptors in surgical specimens from
      patients with NSCLC. METHODS: Transcripts of nuclear retinoid receptors were
      detected in formalin-fixed, paraffin-embedded specimens by use of digoxigenin
      labeled riboprobes specific for RAR alpha, RAR beta, RAR gamma, RXR alpha, RXR
      beta, and RXR gamma for in situ hybridization to histologic specimens from 79
      patients with NSCLC and as control from 17 patients with non-lung cancer. The
      quality and specificity of the digoxigenin-labeled probes were determined by
      northern blotting, and the specificity of the binding of antisense riboprobes was
      verified by use of sense probes as controls. RESULTS: All receptors were
      expressed in at least 89% of control normal bronchial tissue specimens from 17
      patients without a primary lung cancer and in distant normal bronchus specimens
      from patients with NSCLC. RAR alpha, RXR alpha, and RXR gamma were expressed in
      more than 95% of the NSCLC specimens. In contrast, RAR beta, RAR gamma, and RXR
      beta expression was detected in only 42%, 72%, and 76% of NSCLC, respectively.
      CONCLUSIONS: These data suggest that the expression of RAR alpha, RXR alpha, and
      RXR gamma is not altered in NSCLC; however, expression of RAR beta and possibly
      also of RAR gamma and RXR beta is suppressed in a large percentage of patients
      with lung cancer. IMPLICATIONS: The loss of expression of one or more of these
      nuclear retinoid receptors may be associated with lung carcinogenesis.

PMID- 9150187
TI  - Immunoglobulin G responses against human papillomavirus type 16 virus-like
      particles in a prospective nonintervention cohort study of women with cervical
      intraepithelial neoplasia.
AB  - BACKGROUND: Infection with cancer-linked human papillomavirus (HPV) types such as
      HPV type 16 (HPV16) is the most important risk factor in the development of
      cervical cancer. It has been shown that immunoglobulin G (IgG) antibody responses
      against HPV16 virus-like particles (VLPs) are specifically associated with
      genital HPV16 infection. PURPOSE: The aim of this study was to determine the
      temporal relationships between the presence of HPV16 VLP-specific IgGs, HPV16
      infection patterns, and the course of premalignant cervical disease. METHODS:
      Plasma samples from 133 women who had been diagnosed originally with mild to
      moderate cervical dyskaryosis and enrolled in a prospective non-intervention
      cohort study conducted in Amsterdam, The Netherlands, from 1991 through 1996 were
      analyzed for the presence of HPV16 VLP-specific IgGs by use of an enzyme-linked
      immunosorbent assay. A detailed analysis was performed on 43 women with different
      HPV16 infection patterns during a follow-up period of 10-34 months. Progression
      or regression of cervical intraepithelial neoplasia (CIN) lesions was monitored
      by cytologic and colposcopic testing at intervals of 3-4 months. HPV typing in
      cervical smears was performed by use of a polymerase chain reaction-based assay.
      Statistical analysis of the serologic data was performed by use of the Mann
      Whitney U test or 2 x 2 table analyses. RESULTS: The presence of HPV16 VLP
      specific IgGs in the plasma of the patients was found to be associated with the
      presence of HPV16 DNA in the cervical smear. Significantly higher proportions of
      patients with persistent HPV16 infections (i.e., who were polymerase chain
      reaction positive in three to 11 consecutive tests) than of patients with cleared
      HPV16 infections were found to be positive for the presence of HPV16 VLP-specific
      IgGs (18 [69.2%] of 26 versus nine [28.1%] of 32, respectively; P = .003). HPV16
      VLP-specific IgGs were consistently detected in all women (n = 11) who were
      persistently HPV16 DNA positive during follow-up and whose disease ultimately
      progressed to CIN III (histologically diagnosed severe dysplasia or carcinoma in
      situ). CONCLUSION: HPV16 VLP-specific IgG responses are present in the plasma of
      a majority of patients with persistent HPV16 infections and histologically
      confirmed high-grade lesions but only in a smaller subset of patients with
      cleared HPV16 infections and either normal cervical histology or low-grade CIN
      lesions. IMPLICATIONS: These results suggest that HPV16 VLP-specific antibodies
      are not responsible for the clearance of virally induced CIN lesions but that
      they might, in patients with persistent HPV16 infections, be indicative of an
      increased cervical cancer risk.

PMID- 9150188
TI  - Expression of p53, glutathione S-transferase-pi, and Bcl-2 proteins and benefit
      from adjuvant radiotherapy in breast cancer.
AB  - BACKGROUND: In clinical breast cancer research, the utility of certain biomarkers
      as predictors of response to surgery, chemotherapy, or hormonal therapy has been
      studied intensively. Much less research has been done on the relevance of
      biologic predictors of response to radiotherapy, which represents an effective
      local-regional treatment for breast cancer. PURPOSE: The utility of biomarkers
      involved in DNA damage repair (p53 protein), control of programmed cell death
      (p53 and Bcl-2 proteins), and cellular detoxification (glutathione S-transferase
      pi [GST-pi] enzyme) in predicting local breast cancer recurrence was analyzed
      retrospectively in two cohorts of breast cancer patients. These patients had had
      no detectable metastases in the axillary lymph nodes (i.e., node-negative) or in
      distant sites and had had similar distributions of clinicopathologic and biologic
      prognostic features. They had been treated by conservative surgery alone (139
      case patients) or by conservative surgery followed by adjuvant radiotherapy (496
      case patients) during the period from 1984 through 1990. METHODS: The expression
      of the p53, GST-pi, and Bcl-2 proteins in the specimens of primary breast tumor
      obtained from these patients was determined by use of immunohistochemistry; cell
      proliferation activity and levels of steroid receptors were determined by use of
      a [3H]thymidine-labeling index assay and the dextran-coated charcoal technique,
      respectively. The median time of follow-up of patients was 6 years. In the
      analyses of patient outcomes, only local failures that presented as first events
      were considered. RESULTS: After surgery alone, the risk of local recurrence at 6
      years was higher for patients with tumors exhibiting elevated levels of p53 and
      GST-pi protein expression than for patients with low levels (hazard ratio [HR] =
      3.1, 95% confidence interval [CI] = 1.3-7.7, two-sided P = .012; HR = 2.7, 95% CI
      = 1.1-6.4, two-sided P = .026, respectively). Weak or no observable expression of
      Bcl-2 protein was only suggestive of a higher frequency of local failures.
      Adjustment for patient age, tumor size, cell proliferation, and estrogen receptor
      status did not change these findings. Conversely, in the series of patients given
      conservative surgery followed by radiotherapy, there was no difference in local
      tumor recurrence between patients with tumors expressing or not expressing each
      of the three markers. CONCLUSIONS: Our study provides indirect evidence of a
      benefit from radiation therapy in preventing local breast cancer relapse,
      particularly among node-negative patients with tumors that express elevated
      levels of the p53 or GST-pi proteins or that express little or no Bcl-2 protein.

PMID- 9150189
TI  - Interleukin 1-dependent and -independent mouse melanoma metastases.
AB  - BACKGROUND: The adhesion of cancer cells to the endothelial lining of blood
      vessels, which is important for metastasis, is promoted by the action of
      interleukin 1 (IL-1) and other cytokines. PURPOSE: IL-1-producing melanoma cells
      were used to induce metastases in mice to test whether melanoma metastasis-
      wherever it occurs--depends on the action of IL-1. METHODS: We used the following
      experimental designs in this study: 1) Male C57BL/6J mice were inoculated in the
      left cardiac ventricle with 5 x 10(4) murine B16 melanoma cells, and no treatment
      was given (control animals). 2) Mice received an intraperitoneal injection of
      either saline (control animals) or recombinant human IL-1 receptor antagonist
      (rHuIL-1Ra) 2 hours before the injection of cancer cells; thereafter, they
      received an additional injection of saline or rHuIL-1Ra daily for 20 days. 3)
      Mice received an intravenous injection of either saline or rHuIL-1Ra; 15 minutes
      later, mice that received saline were given either a second injection of saline
      (control animals) or an injection of bacterial lipopolysaccharide (LPS) to
      stimulate host IL-1 production and endothelial cell activation. The mice that
      received rHuIL-1Ra were also given an injection of LPS at this time. Six hours
      later, all mice were inoculated with cancer cells, followed by no further
      treatment. In all experiments, the mice were killed 20 days after the injection
      of cancer cells, and metastases were counted in multiple organs and bones.
      Metastasis incidence values (relating to the frequency that a given site was
      positive for metastasis) and metastasis development index values (relating to the
      extent of metastasis at a given site) were calculated. A hierarchical cluster
      analysis was performed to determine whether groups of organs exhibited
      characteristic changes in their metastasis development index values in response
      to the three treatments given (i.e., rHuIL-1Ra, LPS, or rHuIL-1Ra plus LPS).
      Reported P values are two-sided. RESULTS AND CONCLUSIONS: Treatment with rHuIL
      1Ra alone significantly (P<.05) reduced the occurrence of metastasis in the bone
      marrow, spleen, liver, lung, pancreas, skeletal muscle, adrenal gland, and heart,
      indicating that host- and/or melanoma-derived IL-1 promoted metastasis in these
      organs; treatment with rHuIL-1Ra had no effect on metastasis in the kidney,
      testis, brain, skin, and gastrointestinal tract, suggesting that metastasis in
      these latter organs was IL-1 independent. Treatment with LPS alone significantly
      (P<.05) enhanced metastasis in the same organs for which rHuIL-1Ra treatment
      reduced metastasis, except for the heart and the adrenal gland. Treatment with
      rHuIL-1Ra 15 minutes before LPS treatment abrogated the LPS-mediated enhancement
      of metastasis. Two independent organ groups for which IL-1 promoted melanoma
      metastasis were identified in the cluster analysis.

PMID- 9150191
TI  - You say tomato and I say tomahto: getting a handle on pronouncing apoptosis.

PMID- 9150190
TI  - Antiproliferative action of vitamin D-related compounds and insulin-like growth
      factor-binding protein 5 accumulation.
AB  - BACKGROUND AND PURPOSE: Vitamin D-related compounds can inhibit cancer cell
      growth, but the biologic mechanism of this inhibition remains to be determined.
      We investigated the possibility that these compounds interfere with the activity
      of insulin-like growth factors. Such activity can be suppressed or otherwise
      modulated by specific insulin-like growth factor-binding proteins. METHODS: The
      human breast cancer cell line MCF-7 was used in this study. The effects of 1,25
      dihydroxyvitamin D3 [1,25(OH)2D3] and two related compounds, EB1089 and KH1060,
      on cell proliferation were assessed by monitoring cell numbers and by measuring
      cellular incorporation of [3H]thymidine. Changes in the accumulation of insulin
      like growth factor-binding proteins in cell-conditioned media (i.e., culture
      fluids) were assessed by means of standard protein blotting techniques; ligand
      blots were probed with [125I]insulin-like growth factor I, and immunoblots were
      probed with antibodies raised against specific binding proteins. Binding protein
      messenger RNA levels were determined by use of RNA blotting methods and
      complementary DNA probes. RESULTS: At concentrations of 10(-8) M and 10(-9) M,
      EB1089 and KH1060 exhibited stronger antiproliferative activity than 1,25(OH)2D3.
      When each of the vitamin D-related compounds was used separately at a
      concentration of 10(-9) M, a 20- to 25-fold increase in the concentration of
      insulin-like growth factor-binding proteins in MCF-7 cell-conditioned media was
      observed; this binding capacity was increased nine-fold, ninefold, and threefold,
      respectively, in the presence of 10(-10) M EB1089, KH1060, and 1,25(OH)2D3.
      Immunoblotting experiments demonstrated that all three vitamin D-related
      compounds induced the accumulation of insulin-like growth factor-binding protein
      5 in cell-conditioned media. The accumulation of this binding protein was
      associated with an increase in cellular expression of its messenger RNA. EB1089
      and 1,25(OH)2D3 attenuated the growth-promoting activity of insulin-like growth
      factor I on MCF-7 cells; however, these compounds did not inhibit the growth
      promoting activity of long R3 IGF-I, an insulin-like growth factor I analogue
      with greatly reduced affinity for insulin-like growth factor-binding proteins.
      CONCLUSIONS AND IMPLICATIONS: Our results indicate that vitamin D-related
      compounds stimulate production of insulin-like growth factor-binding protein 5,
      thereby indirectly suppressing cell proliferation.

PMID- 9150192
TI  - Second cancers after adjuvant tamoxifen therapy for breast cancer.

PMID- 9150193
TI  - Randomized trial of two versus five years of adjuvant tamoxifen for
      postmenopausal early stage breast cancer.

PMID- 9150194
TI  - Diabetes mellitus and risk of large bowel cancer.

PMID- 9150195
TI  - Reversal of relation between body mass and endogenous estrogen concentrations
      with menopausal status.

PMID- 9150196
TI  - Breast cancer risk in rats fed a diet high in n-6 polyunsaturated fatty acids
      during pregnancy.

PMID- 9150197
TI  - Lung cancer risk from residential radon: meta-analysis of eight epidemiologic
      studies.

PMID- 9150198
TI  - Lung cancer risk from residential radon: meta-analysis of eight epidemiologic
      studies.

PMID- 9150200
TI  - The RIB element in the goaG-pspF intergenic region of Escherichia coli.
AB  - The sequence (2,700 bp) between the aldH and pspF genes of Escherichia coli was
      determined. The pspF gene encodes a sigma54 transcriptional activator of the
      phage shock protein (psp) operon (pspA to pspE). Downstream of the pspF
      transcribed region are two open reading frames (ORFs), ordL and goaG,
      convergently oriented with respect to pspF. These two ORFs, together with the
      adjacent aldH gene, may constitute a novel operon (aldH-ordL-goaG). The goaG-pspF
      intergenic region contains a complex extragenic mosaic element, RIB. The
      structure of this RIB element, which belongs to the BIME-1 family, is Y(REP1) >
      16 < Z1(REP2), where Y and Z1 are palindromic units and the central 16 bases
      contain an L motif with an ihf consensus sequence. DNA fragments containing the L
      motif of the psp RIB element effectively bind integration host factor (IHF),
      while the Y palindromic unit (REP1) of the same RIB element binds DNA gyrase
      weakly. Computer prediction of the pspF mRNA secondary structure suggested that
      the transcribed stem-loop structures formed by the 3'-flanking region of the pspF
      transcript containing the RIB element can stabilize and protect pspF mRNA.
      Analysis of pspF steady-state mRNA levels showed that transcripts with an intact
      RIB element are much more abundant than those truncated at the 3' end by deletion
      of either the entire RIB element or a single Z1 sequence (REP2). Thus, the pspF
      3'-flanking region containing the RIB element has an important role in the
      stabilization of the pspF transcript.

PMID- 9150199
TI  - Agrobacterium tumefaciens T-complex transport apparatus: a paradigm for a new
      family of multifunctional transporters in eubacteria.

PMID- 9150201
TI  - The htpG gene of Bacillus subtilis belongs to class III heat shock genes and is
      under negative control.
AB  - We show that the htpG gene of Bacillus subtilis is induced by heat, as has been
      reported for the Escherichia coli homolog. Analysis of different mutants revealed
      that the htpG gene belongs to class III heat shock genes in B. subtilis. An about
      10-fold induction after thermal upshock was found at the levels of both
      transcription and translation, and this induction resulted from enhanced
      synthesis of mRNA. By primer extension, we identified one potential transcription
      start site immediately downstream of a putative sigmaA-dependent promoter which
      became activated after thermal upshift. Northern blot analysis revealed that htpG
      is part of a monocistronic transcriptional unit. An operon fusion where the
      complete region between htpG and its upstream gene was fused to the bgaB reporter
      gene accurately reflected htpG expression. Analysis of this fusion revealed that,
      in contrast to other class III heat shock genes, htpG was not induced by osmotic
      upshock, by ethanol, or by oxygen limitation, suggesting that it belongs to a
      subgroup within class III. Deletion of the region upstream of the putative
      promoter resulted in an enhanced basal level of htpG expression, but the 10-fold
      induction was retained, suggesting that the upstream sequences are involved in
      the regulation of expression in the absence of heat shock.

PMID- 9150202
TI  - Characterization of three protein components required for functional
      reconstitution of the epoxide carboxylase multienzyme complex from Xanthobacter
      strain Py2.
AB  - Epoxide carboxylase from Xanthobacter strain Py2 catalyzes the reductant- and
      NAD+-dependent carboxylation of aliphatic epoxides to beta-keto acids. Epoxide
      carboxylase from Xanthobacter strain Py2 has been resolved from cell extracts by
      anion-exchange chromatography into three protein components, designated I, II,
      and III, that are obligately required for functional reconstitution of epoxide
      carboxylase activity. Component II has been purified to homogeneity on the basis
      of its ability to complement components I and III in restoring epoxide
      carboxylase activity. Purified component II had a specific activity for epoxide
      carboxylation of 41.8 mU x min(-1) x mg(-1) when components I and III were
      present at saturating levels. The biochemical properties of component II reveal
      that it is the flavin-containing NADPH:disulfide oxidoreductase that was recently
      shown by other means to be associated with epoxide degradation activity in
      Xanthobacter strain Py2 (J. Swaving, J. A. M. de Bont, A. Westphal, and A. Dekok,
      J. Bacteriol. 178:6644-6646, 1996). The rate of epoxide carboxylation was
      dependent on the relative concentrations of the three carboxylase components. At
      fixed concentrations of two of the components, epoxide carboxylation rates were
      saturated in a hyperbolic fashion by increasing the concentration of the third
      variable component. Methylepoxypropane has been characterized as a time
      dependent, irreversible inactivator of epoxide carboxylase activity that is
      proposed to be a mechanism-based inactivator of the enzyme. The addition of
      component I, but not that of component II or III, to methylepoxypropane
      inactivated cell extracts restored epoxide carboxylase activity, suggesting that
      component I contains the epoxide binding and activation sites.

PMID- 9150203
TI  - The disulfide bond in the Aeromonas hydrophila lipase/acyltransferase stabilizes
      the structure but is not required for secretion or activity.
AB  - Vibrio and Aeromonas spp. secrete an unusual 35-kDa lipase that shares several
      properties with mammalian lecithin-cholesterol acyltransferase. The Aeromonas
      hydrophila lipase contains two cysteine residues that form an intramolecular
      disulfide bridge. Here we show that changing either of the cysteines to serine
      does not reduce enzymatic activity, indicating that the disulfide bond is not
      required for correct folding. However, when either of the cysteines is replaced,
      the enzyme is more readily denatured by urea and more sensitive to degradation by
      trypsin than is the wild-type enzyme, evidence that the bridge has an important
      role in stabilizing the protein's structure. The two mutant proteins with serine
      for-cysteine replacements were secreted by Aeromonas salmonicida containing the
      cloned genes, although the levels of both in the culture supernatants were lower
      than the level of the wild-type enzyme. When the general secretory pathway was
      blocked with carbonyl cyanide chlorophenylhydrazone, the cell-associated pools of
      the mutant enzymes appeared to be degraded, whereas the wild-type pool remained
      stable. We conclude that reduced extracellular levels of the mutant proteins are
      the result of their increased sensitivities to proteases encountered inside the
      cell during export.

PMID- 9150204
TI  - comYA, a gene similar to comGA of Bacillus subtilis, is essential for competence
      factor-dependent DNA transformation in Streptococcus gordonii.
AB  - Tn4001 mutagenesis identified a new competence gene in Streptococcus gordonii
      Challis designated comYA. A comYA mutant was completely deficient in
      transformation and exhibited decreased levels of DNA binding and hydrolysis. The
      deduced 319-amino-acid ComYA protein exhibited 57% similarity and 33% identity to
      the ComGA transporter protein of Bacillus subtilis and contained the Walker A-box
      motif conserved in ATP-binding proteins as well as aspartic acid boxes Asp-1 and
      Asp-2 present in some components of the general secretory pathway of gram
      negative bacteria. comYA appeared to be part of a putative operon encompassing a
      comGB homolog, designated comYB, together with sequences that could encode ComGC-
      and ComGD-like peptides designated ComYC and ComYD, respectively, as well as
      other components. The putative ComYC and ComYD peptides had leader sequences
      similar to the type IV N-methylphenylalanine pilins of gram-negative bacteria,
      but unlike other examples in this class, including B. subtilis, they contained an
      alanine at position -1 of the leader instead of the usual glycine residue.
      Northern analysis identified a single 6.0-kb comYA-containing transcript strictly
      dependent on exogenous competence factor for expression in ComA1 cells. An
      identical pattern of expression was seen in wild-type Challis cells grown under
      conditions of maximal competence but not in cells that were noncompetent.

PMID- 9150205
TI  - Regulation of las and rhl quorum sensing in Pseudomonas aeruginosa.
AB  - The production of several virulence factors by Pseudomonas aeruginosa is
      controlled according to cell density through two quorum-sensing systems, las and
      rhl. The las system is comprised of the transcriptional activator protein LasR
      and of LasI, which directs the synthesis of the autoinducer PAI-1. Similarly, the
      rhl system consists of the transcriptional activator protein RhlR and of RhlI,
      which directs synthesis of the autoinducer PAI-2 (formerly referred to as factor
      2). To study the interrelation between the two P. aeruginosa quorum-sensing
      systems, we fused a lacZ reporter gene to lasR, rhlR, and rhlA and monitored
      expression of these three genes under various conditions. Our data indicate that
      lasR and rhlR are expressed in a growth-dependent manner, with activation of each
      gene occurring during the last half of log-phase growth. We also show that the
      las quorum-sensing system controls the rhl quorum-sensing system in two ways.
      First, we found that LasR and PAI-1 activated rhlR transcription. Second, we
      showed that PAI-1 blocked PAI-2 from binding to RhlR, thereby inhibiting the
      expression of rhlA. Our data thus indicate that the las system exerts two levels
      of control on RhlR, transcriptional and posttranslational.

PMID- 9150206
TI  - Menaquinone (vitamin K2) biosynthesis: overexpression, purification, and
      characterization of a new isochorismate synthase from Escherichia coli.
AB  - The first committed step in the biosynthesis of menaquinone (vitamin K2) is the
      conversion of chorismate to isochorismate, which is mediated by an isochorismate
      synthase encoded by the menF gene. This isochorismate synthase (MenF) is distinct
      from the entC-encoded isochorismate synthase (EntC) involved in enterobactin
      biosynthesis. MenF has been overexpressed under the influence of the T7 promoter
      and purified to homogeneity. The purified protein was found to have a molecular
      mass of 98 kDa as determined by gel filtration column chromatography on Sephacryl
      S-200. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a
      molecular mass of 48 kDa. Thus, the enzyme is a homodimer. The purified enzyme
      showed a pH optimum of 7.5 to 8.0 and a temperature optimum of 37 degrees C. The
      enzyme carries out the irreversible conversion of chorismate to isochorismate in
      the presence of Mg2+. The enzyme was found to have a Km of 195 +/- 23 microM and
      a k(cat) of 80 min(-1). In the presence of 30 mM beta-mercaptoethanol (BME), the
      k(cat) increased to 176 min(-1). The reducing agents BME and dithiothreitol
      stimulated the enzymatic activity more than twofold. Treatment of the enzyme with
      the cysteine-specific modifying reagent N-ethylmaleimide (NEM) resulted in the
      complete loss of activity. Preincubation of the enzyme with the substrate,
      chorismate, before NEM treatment resulted in complete protection of the enzyme
      from inactivation.

PMID- 9150207
TI  - An alkB gene homolog is differentially transcribed during the Caulobacter
      crescentus cell cycle.
AB  - A Caulobacter crescentus alkB gene homolog was identified in a clone previously
      shown to contain the heat shock genes dnaK and dnaJ; the homolog is located
      upstream of dnaK and is transcribed in the opposite orientation. An analysis of
      the alkB gene has shown that the deduced amino acid sequence is that of a 21-kDa
      protein, which is 42% identical and 78% similar to Escherichia coli AlkB.
      Furthermore, an alkB-null mutant was constructed by gene disruption and was shown
      to be highly sensitive to the alkylating agent methyl methanesulfonate (MMS).
      However, the alkB gene of C. crescentus, unlike its E. coli counterpart, is not
      located downstream of the ada gene, and its transcription is not induced by
      alkylating agents. In addition, no acquired enhanced resistance to MMS toxicity
      by treatment with low MMS doses was observed, suggesting that no adaptive
      response occurs in C. crescentus. Nevertheless, transcription of the alkB gene is
      cell cycle controlled, with a pattern of expression similar to that of several
      Caulobacter genes involved in DNA replication.

PMID- 9150208
TI  - 2-Sulfotrehalose, a novel osmolyte in haloalkaliphilic archaea.
AB  - A novel 1-->1 alpha-linked glucose disaccharide with sulfate at C-2 of one of the
      glucose moieties, 1-(2-O-sulfo-alpha-D-glucopyranosyl)-alpha-D-glycopyranose, was
      found to be the major organic solute accumulated by a Natronococcus sp. and
      several Natronobacterium species. The concentration of this novel disaccharide,
      termed sulfotrehalose, increased with increasing concentrations of external NaCl,
      behavior consistent with its identity as an osmolyte. A variety of noncharged
      disaccharides (trehalose, sucrose, cellobiose, and maltose) were added to the
      growth medium to see if they could suppress synthesis and accumulation of
      sulfotrehalose. Sucrose was the most effective in suppressing biosynthesis and
      accumulation of sulfotrehalose, with levels as low as 0.1 mM being able to
      significantly replace the novel charged osmolyte. Other common osmolytes (glycine
      betaine, glutamate, and proline) were not accumulated or used for osmotic balance
      in place of the sulfotrehalose by the halophilic archaeons.

PMID- 9150209
TI  - Differential patterns of activity displayed by two exo-beta-1,3-glucanases
      associated with the Aspergillus fumigatus cell wall.
AB  - Two exo-beta-1,3-glucanases (herein designated exoG-I and exoG-II) were isolated
      from the cell wall autolysate of the filamentous fungus Aspergillus fumigatus and
      purified by ion-exchange, hydrophobic-interaction, and gel filtration
      chromatographies. Molecular masses estimated by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and gel filtration chromatography were 82 kDa
      for the monomeric exoG-I and 230 kDa for the dimeric exoG-II. exoG-I and exoG-II
      were glycosylated, and N glycans accounted, respectively, for 2 and 44 kDa. Their
      pH optimum is 5.0. Their optimum temperatures are 55 degrees C for exoG-I and 65
      degrees C for exoG-II. By a sensitive colorimetric method and high-performance
      anion-exchange chromatography for product analysis, two patterns of exo-beta-1,3
      glucanase activities were found. The 230-kDa exoG-II enzyme acts on p-nitrophenyl
      beta-D-glucoside, beta-1,6-glucan, and beta-1,3-glucan. This activity, which
      retains the anomeric configuration of glucose released, presented a multichain
      pattern of attack of the glucan chains and a decrease in the maximum initial
      velocity (Vm) with the increasing size of the substrate. In contrast, the 82-kDa
      exoG-I, which inverts the anomeric configuration of the glucose released,
      hydrolyzed exclusively the beta-1,3-glucan chain with a minimal substrate size of
      4 glucose residues. This enzyme presented a repetitive-attack pattern,
      characterized by an increase in Vm with an increase in substrate size and by a
      degradation of the glucan chain until it reached laminaritetraose, the limit
      substrate size. The 82-kDa exoG-I and 230-kDa exoG-II enzymes correspond to a
      beta-1,3-glucan-glucohydrolase (EC 3.2.1.58) and to a beta-D-glucoside
      glucohydrolase (EC 3.2.1.21), respectively. The occurrence and functions of these
      two classes of exo-beta-1,3-glucanases in other fungal species are discussed.

PMID- 9150210
TI  - Paraquat regulation of hmp (flavohemoglobin) gene expression in Escherichia coli
      K-12 is SoxRS independent but modulated by sigma S.
AB  - We report the first example of a gene, hmp, encoding a soluble flavohemoglobin in
      Escherichia coli K-12, which is up-regulated by paraquat in a SoxRS-independent
      manner. Unlike what is found for other paraquat-inducible genes, high
      concentrations of paraquat (200 microM) were required to increase the level of
      hmp expression, and maximal induction was observed only after 20 min of exposure
      to paraquat. Neither a mutation in soxS nor one in soxR prevented the paraquat
      dependent increase in phi(hmp-lacZ) expression, but either mutant allele delayed
      full expression of phi(hmp-lacZ) activity after paraquat addition. Induction of
      hmp by paraquat was demonstrated in aerobically grown cultures during exponential
      growth and the stationary phase, thus revealing two Sox-independent regulatory
      mechanisms. Induction of hmp by paraquat in the stationary phase was dependent on
      the global regulator of stationary-phase gene expression, RpoS (sigma S).
      However, a mutation in rpoS did not prevent an increase in hmp expression by
      paraquat in exponentially growing cells. Induction of sigma S in the exponential
      phase by heat shock also induced phi(hmp-lacZ) expression in the presence of
      paraquat, supporting the role of sigma S in one of the regulatory mechanisms.
      Mutations in oxyR or rob, known regulators of several stress promoters in E.
      coli, had no effect on the induction of hmp by paraquat. Other known superoxide
      generating agents (plumbagin, menadione, and phenazine methosulfate) were not
      effective in inducing hmp expression.

PMID- 9150211
TI  - p-Cymene catabolic pathway in Pseudomonas putida F1: cloning and characterization
      of DNA encoding conversion of p-cymene to p-cumate.
AB  - Pseudomonas putida F1 utilizes p-cymene (p-isopropyltoluene) by an 11-step
      pathway through p-cumate (p-isopropylbenzoate) to isobutyrate, pyruvate, and
      acetyl coenzyme A. The cym operon, encoding the conversion of p-cymene to p
      cumate, is located just upstream of the cmt operon, which encodes the further
      catabolism of p-cumate and is located, in turn, upstream of the tod (toluene
      catabolism) operon in P. putida F1. The sequences of an 11,236-bp DNA segment
      carrying the cym operon and a 915-bp DNA segment completing the sequence of the
      2,673-bp DNA segment separating the cmt and tod operons have been determined and
      are discussed here. The cym operon contains six genes in the order cymBCAaAbDE.
      The gene products have been identified both by functional assays and by comparing
      deduced amino acid sequences to published sequences. Thus, cymAa and cymAb encode
      the two components of p-cymene monooxygenase, a hydroxylase and a reductase,
      respectively; cymB encodes p-cumic alcohol dehydrogenase; cymC encodes p-cumic
      aldehyde dehydrogenase; cymD encodes a putative outer membrane protein related to
      gene products of other aromatic hydrocarbon catabolic operons, but having an
      unknown function in p-cymene catabolism; and cymE encodes an acetyl coenzyme A
      synthetase whose role in this pathway is also unknown. Upstream of the cym operon
      is a regulatory gene, cymR. By using recombinant bacteria carrying either the
      operator-promoter region of the cym operon or the cmt operon upstream of genes
      encoding readily assayed enzymes, in the presence or absence of cymR, it was
      demonstrated that cymR encodes a repressor which controls expression of both the
      cym and cmt operons and is inducible by p-cumate but not p-cymene. Short (less
      than 350 bp) homologous DNA segments that are located upstream of cymR and
      between the cmt and tod operons may have been involved in recombination events
      that led to the current arrangement of cym, cmt, and tod genes in P. putida F1.

PMID- 9150212
TI  - Molecular characterization of a germination-specific muramidase from Clostridium
      perfringens S40 spores and nucleotide sequence of the corresponding gene.
AB  - The exudate of fully germinated spores of Clostridium perfringens S40 in 0.15 M
      KCI-50 mM potassium phosphate (pH 7.0) was found to contain another spore-lytic
      enzyme in addition to the germination-specific amidase previously characterized
      (S. Miyata, R. Moriyama, N. Miyahara, and S. Makino, Microbiology 141:2643-2650,
      1995). The lytic enzyme was purified to homogeneity by anion-exchange
      chromatography and shown to be a muramidase which requires divalent cations
      (Ca2+, Mg2+, or Mn2+) for its activity. The enzyme was inactivated by sulfhydryl
      reagents, and sodium thioglycolate reversed the inactivation by Hg2+. The
      muramidase hydrolyzed isolated spore cortical fragments from a variety of wild
      type organisms but had minimal activity on decoated spores and isolated cell
      walls. However, the enzyme was not capable of digesting isolated cortical
      fragments from spores of Bacillus subtilis ADD1, which lacks muramic acid delta
      lactam in its cortical peptidoglycan. This indicates that the enzyme recognizes
      the delta-lactam residue peculiar to spore peptidoglycan, suggesting an
      involvement of the enzyme in spore germination. Immunochemical studies indicated
      that the muramidase in its mature form is localized on the exterior of the cortex
      layer in the dormant spore. A gene encoding the muramidase, sleM, was cloned into
      Escherichia coli, and the nucleotide sequence was determined. The gene encoded a
      protein of 321 amino acids with a deduced molecular weight of 36,358. The deduced
      amino acid sequence of the sleM gene indicated that the enzyme is produced in a
      mature form. It was suggested that the muramidase belongs to a separate group
      within the lysozyme family typified by the fungus Chalaropsis lysozyme. A
      possible mechanism for cortex degradation in C. perfringens S40 spores is
      discussed.

PMID- 9150213
TI  - Molecular characterization and cellular localization of TpLRR, a processed
      leucine-rich repeat protein of Treponema pallidum, the syphilis spirochete.
AB  - Automated Edman degradation was used to obtain N-terminal and internal amino acid
      sequences from a 26-kDa protein in isolated Treponema pallidum outer membranes
      (OMs). The resulting sequences enabled us to PCR amplify from T. pallidum DNA a
      275-bp fragment of the corresponding gene. The complete nucleotide sequence of
      the gene was determined from fragments amplified by long-distance PCR. Primer
      extension verified the assigned translational start of the open reading frame
      (ORF) and putative upstream promoter elements. The ORF encoded a highly basic (pI
      9.6) 26-kDa protein which contained an N-terminal 25-amino-acid leader peptide
      terminated by a signal peptidase I cleavage site. The mature protein contained
      seven tandemly spaced copies (as well as an eighth incomplete copy) of a leucine
      rich repeat (LRR), a motif previously identified in a number of prokaryotic and
      eukaryotic proteins. Accordingly, the polypeptide was designated T. pallidum
      leucine-rich repeat protein (TpLRR). Although Triton X-114 phase partitioning
      showed that TpLRR was hydrophilic, cell localization studies showed that most of
      the antigen was associated with the peptidoglycan-cytoplasmic membrane complex
      rather than being freely soluble in the periplasmic space. Immunoblot studies
      showed that syphilis patients develop a weak antibody response to the antigen.
      Lastly, the lrr(T. pallidum) gene was mapped to a 60-kb SfiI-SpeI fragment of the
      T. pallidum chromosome which also contains the rrnA and flaA genes. The
      function(s) of TpLRR is currently unknown; however, protein-protein and/or
      protein-lipid interactions mediated by its LRR motifs may facilitate interactions
      between components of the T. pallidum cell envelope.

PMID- 9150214
TI  - Glycerol elicits energy taxis of Escherichia coli and Salmonella typhimurium.
AB  - Escherichia coli and Salmonella typhimurium show positive chemotaxis to glycerol,
      a chemical previously reported to be a repellent for E. coli. The threshold of
      the attractant response in both species was 10(-6) M glycerol. Glycerol
      chemotaxis was energy dependent and coincident with an increase in membrane
      potential. Metabolism of glycerol was required for chemotaxis, and when lactate
      was present to maintain energy production in the absence of glycerol, the
      increases in membrane potential and chemotactic response upon addition of
      glycerol were abolished. Methylation of a chemotaxis receptor was not required
      for positive glycerol chemotaxis in E. coli or S. typhimurium but is involved in
      the negative chemotaxis of E. coli to high concentrations of glycerol. We propose
      that positive chemotaxis to glycerol in E. coli and S. typhimurium is an example
      of energy taxis mediated via a signal transduction pathway that responds to
      changes in the cellular energy level.

PMID- 9150215
TI  - A role for Salmonella typhimurium cbiK in cobalamin (vitamin B12) and siroheme
      biosynthesis.
AB  - The role of cbiK, a gene found encoded within the Salmonella typhimurium cob
      operon, has been investigated by studying its in vivo function in Escherichia
      coli. First, it was found that cbiK is not required for cobalamin biosynthesis in
      the presence of a genomic cysG gene (encoding siroheme synthase) background.
      Second, in the absence of a genomic cysG gene, cobalamin biosynthesis in E. coli
      was found to be dependent upon the presence of cobA(P. denitrificans) (encoding
      the uroporphyrinogen III methyltransferase from Pseudomonas denitrificans) and
      cbiK. Third, complementation of the cysteine auxotrophy of the E. coli cysG
      deletion strain 302delta a could be attained by the combined presence of cobA(P.
      denitrificans) and the S. typhimurium cbiK gene. Collectively these results
      suggest that CbiK can function in fashion analogous to that of the N-terminal
      domain of CysG (CysG(B)), which catalyzes the final two steps in siroheme
      synthesis, i.e., NAD-dependent dehydrogenation of precorrin-2 to sirohydrochlorin
      and ferrochelation. Thus, phenotypically CysG(B) and CbiK have very similar
      properties in vivo, although the two proteins do not have any sequence
      similarity. In comparison to CysG, CbiK appears to have a greater affinity for
      Co2+ than for Fe2+, and it is likely that cbiK encodes an enzyme whose primary
      role is that of a cobalt chelatase in corrin biosynthesis.

PMID- 9150216
TI  - Regions of Escherichia coli TonB and FepA proteins essential for in vivo physical
      interactions.
AB  - The transport of Fe(III)-siderophore complexes and vitamin B12 across the outer
      membrane of Escherichia coli is an active transport process requiring a cognate
      outer membrane receptor, cytoplasmic membrane-derived proton motive force, and an
      energy-transducing protein anchored in the cytoplasmic membrane, TonB. This
      process requires direct physical contact between the outer membrane receptor and
      TonB. Previous studies have identified an amino-terminally located region (termed
      the TonB box) conserved in all known TonB-dependent outer membrane receptors as
      being essential for productive energy transduction. In the present study, a
      mutation in the TonB box of the ferric enterochelin receptor FepA resulted in the
      loss of detectable in vivo chemical cross-linking between FepA and TonB. Protease
      susceptibility studies indicated this effect was due to an alteration of
      conformation rather than the direct disruption of a specific site of physical
      contact. This suggested that TonB residue 160, implicated in previous studies as
      a site of allele-specific suppression of TonB box mutants, also made a
      conformational rather than a direct contribution to the physical interaction
      between TonB and the outer membrane receptors. This possibility was supported by
      the finding that TonB carboxyl-terminal truncations that retained Gln-160 were
      unable to participate in TonB-FepA complex formation, indicating that this site
      alone was not sufficient to support the physical interactions involved in energy
      transduction. These studies indicated that the final 48 residues of TonB were
      essential to this physical interaction. This region contains a putative
      amphipathic helix which could facilitate TonB-outer membrane interaction. Amino
      acid replacements at one site in this region were found to affect energy
      transduction but did not appear to greatly alter TonB conformation or the
      formation of a TonB-FepA complex. The effects of amino acid substitutions at
      several other TonB sites were also examined.

PMID- 9150217
TI  - The Streptomyces galP1 promoter has a novel RNA polymerase recognition sequence
      and is transcribed by a new form of RNA polymerase in vitro.
AB  - We report the identification of DNA sequences that determine the activity of the
      Streptomyces galP1 promoter and a new form of RNA polymerase holoenzyme that
      recognizes these sequences in vitro. Base substitutions were introduced
      throughout the galP1 promoter region, and bases at positions -34, -36, and -11
      with respect to the transcription start site were shown to be required for
      promoter function. These bases correspond in their positions to regions known to
      be important for RNA polymerase binding in several classes of eubacterial
      promoters, but the sequences themselves are not similar to those previously
      described. The -35 region of the galP1 promoter consists of six G residues, and
      base changes in this G hexamer had a dramatic effect on promoter activity. By
      using galP1-containing DNA template, a new RNA polymerase activity was purified
      from Streptomyces. Holoenzyme reconstitution experiments identified a new sigma
      factor that directs galP1 transcription in vitro. DNase I protection experiments
      identified a binding site for this new holoenzyme immediately upstream of the
      galP1 transcription start site.

PMID- 9150219
TI  - Comparative studies of the phage T2 and T4 DNA (N6-adenine)methyltransferases:
      amino acid changes that affect catalytic activity.
AB  - The bacteriophage T2 and T4 dam genes code for a DNA (N6
      adenine)methyltransferase (MTase). Nonglucosylated, hydroxymethylcytosine
      containing T2gt- virion DNA has a higher level of methylation than T4gt- virion
      DNA does. To investigate the basis for this difference, we compared the
      intracellular enzyme levels following phage infection as well as the in vitro
      intrinsic methylation capabilities of purified T2 and T4 Dam MTases. Results from
      Western blotting (immunoblotting) showed that the same amounts of MTase protein
      were produced after infection with T2 and T4. Kinetic analyses with purified
      homogeneous enzymes showed that the two MTases had similar Km values for the
      methyl donor, S-adenosyl-L-methionine, and for substrate DNA. In contrast, they
      had different k(cat) values (twofold higher for T2 Dam MTase). We suggest that
      this difference can account for the ability of T2 Dam to methylate viral DNA in
      vivo to a higher level than does T4 Dam. Since the T2 and T4 MTases differ at
      only three amino acid residues (at positions 20 [T4, Ser; T2, Pro], 26 [T4, Asn;
      T2, Asp], and 188 [T4, Asp; T2, Glu]), we have produced hybrid proteins to
      determine which residue(s) is responsible for increased catalytic activity. The
      results of these analyses showed that the residues at positions 20 and 26 are
      responsible for the different k(cat) values of the two MTases for both canonical
      and noncanonical sites. Moreover, a single substitution of either residue 20 or
      26 was sufficient to increase the k(cat) of T4 Dam.

PMID- 9150218
TI  - Polymorphism, duplication, and IS1-mediated rearrangement in the chromosomal his
      rfb-gnd region of Escherichia coli strains with group IA and capsular K antigens.
AB  - Individual Escherichia coli strains produce several cell surface polysaccharides.
      In E. coli E69, the his region of the chromosome contains the rfb (serotype O9
      lipopolysaccharide O-antigen biosynthesis) and cps (serotype K30 group IA
      capsular polysaccharide biosynthesis) loci. Polymorphisms in this region of the
      Escherichia coli chromosome reflect extensive antigenic diversity in the species.
      Previously, we reported a duplication of the manC-manB genes, encoding enzymes
      involved in GDP-mannose formation, upstream of rfb in strain E69 (P. Jayaratne et
      al., J. Bacteriol. 176:3126-3139, 1994). Here we show that one of the manC-manB
      copies is flanked by IS1 elements, providing a potential mechanism for the gene
      duplication. Adjacent to manB1 on the IS1-flanked segment is a further open
      reading frame (ugd), encoding uridine-5'-diphosphoglucose dehydrogenase. The Ugd
      enzyme is responsible for the production of UDP-glucuronic acid, a precursor
      required for K30 antigen synthesis. Construction of a chromosomal ugd::Gm(r)
      insertion mutation demonstrated the essential role for Ugd in the biosynthesis of
      the K30 antigen and confirmed that there is no additional functional ugd copy in
      strain E69. PCR amplification and Southern hybridization were used to examine the
      distribution of IS1 elements and ugd genes in the vicinity of rfb in other E.
      coli strains, producing different group IA K antigens. The relative order of
      genes and, where present, IS1 elements was established in these strains. The
      regions adjacent to rfb in these strains are highly variable in both size and
      gene order, but in all cases where a ugd homolog was present, it was found near
      rfb. The presence of IS1 elements in the rfb regions of several of these strains
      provides a potential mechanism for recombination and deletion events which could
      contribute to the antigenic diversity seen in surface polysaccharides.

PMID- 9150220
TI  - Genome structure and phylogeny in the genus Brucella.
AB  - PacI and SpeI restriction maps were obtained for the two chromosomes of each of
      the six species of the genus Brucella: B. melitensis, B. abortus, B. suis, B.
      canis, B. ovis, and B. neotomae. Three complementary techniques were used:
      hybridization with the two replicons as probes, cross-hybridization of
      restriction fragments, and a new mapping method. For each type strain, a unique I
      SceI site was introduced in each of the two replicons, and the location of SpeI
      sites was determined by linearization at the unique site, partial digestion, and
      end labeling of the fragments. The restriction and genetic maps of the six
      species were highly conserved. However, numerous small insertions or deletions,
      ranging from 1 to 34 kb, were observed by comparison with the map of the
      reference strain of the genus, B. melitensis 16M. A 21-kb Spel fragment specific
      to B. ovis was found in the small chromosome of this species. A 640-kb inversion
      was demonstrated in the B. abortus small chromosome. All of these data allowed
      the construction of a phylogenetic tree, which reflects the traditional phenetic
      classification of the genus.

PMID- 9150221
TI  - Regulation of transfer of the Enterococcus faecalis pheromone-responding plasmid
      pAD1: temperature-sensitive transfer mutants and identification of a new
      regulatory determinant, traD.
AB  - The enterococcal, conjugative, cytolysin plasmid pAD1 confers a mating response
      to the peptide sex pheromone cAD1 secreted by plasmid-free strains of
      Enterococcus faecalis. Cells carrying pAM714, a pAD1::Tn917 derivative with wild
      type conjugation properties, were mutagenized with ethyl methanesulfonate to
      obtain variants that were induced (in the absence of pheromone) to transfer
      plasmid DNA upon shifting from 32 to 42 degrees C. Of 31 such mutants generated,
      the results of analyses of 7 are presented in detail. All seven strains were
      thermosensitive in the E. faecalis host FA2-2; colony morphology, clumping, and
      DNA transfer correlated well with each other at the two temperatures. In the
      nonisogenic host E. faecalis OG1X, however, only one derivative (pAM2725)
      exhibited correlation of all three traits at both temperatures. Three (pAM2700,
      pAM2703, and pAM2717) clumped and had colonies characteristic of pheromone
      induced cells at 32 degrees C but transferred plasmid DNA at a higher frequency
      only at the elevated temperature. The other three (pAM2708, pAM2709, and pAM2712)
      were derepressed at both temperatures for all three characteristics. Four of the
      mutations, including that of pAM2725, mapped within the traA determinant, whereas
      two mapped identically in a previously unnoted open reading frame (designated
      traD) putatively encoding a short (23-amino-acid) peptide downstream of the
      inhibitor peptide determinant iad and in the opposite orientation. One mutant
      could not be located in the regions sequenced. Studies showed that the traA and
      traD mutations could be complemented in trans with a DNA fragment carrying the
      corresponding regions.

PMID- 9150223
TI  - The actinomycete Thermobispora bispora contains two distinct types of
      transcriptionally active 16S rRNA genes.
AB  - Here we present the first description of the presence of two distinct types of
      16S rRNA genes in the genome of a (eu)bacterium, Thermobispora bispora. We cloned
      and determined the nucleotide sequences of all four rRNA operons of T. bispora.
      Sequence comparisons revealed that the genome of T. bispora contains two distinct
      types of 16S rRNA genes, each type consisting of two identical or nearly
      identical copies, and three identical copies of the 23S RNA gene. The nucleotide
      sequences of the two types of 16S rRNA genes differ at 98 nucleotide positions
      (6.4% of total nucleotides) together with six regions of deletion-insertions.
      None of the base substitutions or insertion-deletions corresponds to any of the
      approximately 600 evolutionarily invariable or rarely variable nucleotides,
      indicating that both genes are functional. Both types of 16S rRNA genes are
      transcribed and processed as determined by Northern (RNA) hybridization and
      reverse transcriptase-mediated PCR.

PMID- 9150222
TI  - Defective export in Escherichia coli caused by DsbA'-PhoA hybrid proteins whose
      DsbA' domain cannot fold into a conformation resistant to periplasmic proteases.
AB  - The disulfide bond-forming factor DsbA and the alkaline phosphatase are stable in
      the Escherichia coli periplasmic space and can be overproduced without
      significant perturbation of the cell's physiology. By contrast, DsbA'-PhoA hybrid
      proteins resulting from TnphoA insertions into different regions of a plasmid
      borne dsbA gene could become toxic (lethal) to bacteria. Toxicity was concomitant
      with an impairment of some step of the export mechanism and depended on at least
      three parameters, i.e., (i) the rate of expression of the hybrid protein, (ii)
      the ability of the amino-terminal DsbA' domain of the hybrid protein to fold into
      a protease-resistant conformation in the periplasmic space, and (iii) the
      activity of the DegP periplasmic protease. Even under viable conditions of low
      expression, DsbA' folding-deficient hybrid proteins accumulated more than the
      folding-proficient ones in the insoluble material and this was aggravated in a
      strain lacking the DegP protease. When production was more elevated, the folding
      deficient hybrid proteins became lethal, but only in strains lacking the DegP
      activity, while the folding-proficient ones were not. Under conditions of very
      high production by degP+ or degP strains, both types of hybrid proteins
      accumulated as insoluble preproteins. Meanwhile, the export machinery was
      dramatically handicapped and the cells lost viability. However, the folding
      deficient hybrid proteins had a higher killing efficiency than the folding
      proficient ones. Free DsbA'-truncated polypeptides, although not toxic, were
      processed more slowly when they could not fold into a protease-resistant form in
      the periplasmic space. This provides indications in E. coli for a direct or
      indirect influence of the folding of a protein in the periplasmic environment on
      export efficiency.

PMID- 9150224
TI  - NAD-dependent cross-linking of dinitrogenase reductase and dinitrogenase
      reductase ADP-ribosyltransferase from Rhodospirillum rubrum.
AB  - Chemical cross-linking of dinitrogenase reductase and dinitrogenase reductase ADP
      ribosyltransferase (DRAT) from Rhodospirillum rubrum has been investigated with a
      cross-linking system utilizing two reagents, 1-ethyl-3-(3-dimethylaminopropyl)
      carbodiimide and sulfo-N-hydroxysuccinimide. Cross-linking between dinitrogenase
      reductase and DRAT requires the presence of NAD, the cellular ADP-ribose donor,
      or a NAD analog containing an unmodified nicotinamide group, such as nicotinamide
      hypoxanthine dinucleotide. NADP, which will not replace NAD in the modification
      reaction, does support cross-linking between dinitrogenase reductase and DRAT.
      The DRAT-catalyzed ADP-ribosylation of dinitrogenase reductase is inhibited by
      sodium chloride, as is the cross-linking between dinitrogenase reductase and
      DRAT, suggesting that ionic interactions are required for the association of
      these two proteins. Cross-linking is specific for native, unmodified
      dinitrogenase reductase, in that both oxygen-denatured and ADP-ribosylated
      dinitrogenase reductase fail to form a cross-linked complex with DRAT. The ADP
      bound and adenine nucleotide-free states of dinitrogenase reductase form cross
      linked complexes with DRAT; however, cross-linking is inhibited when
      dinitrogenase reductase is in its ATP-bound state.

PMID- 9150226
TI  - Plasmid-homologous sequences in the chromosome of plasmidless Coxiella burnetii
      Scurry Q217.
AB  - Chromosomal DNA from Coxiella burnetii Scurry Q217 was screened for the presence
      of plasmid-homologous sequences. Total DNA from Scurry Q217 was digested with
      NotI, and the resulting DNA fragments were separated by contour-clamped
      homogeneous electric field pulsed-field gel electrophoresis (CHEF-PFGE).
      Following hybridization with biotin-labeled QpH1 plasmid as a probe, two DNA
      fragments of 40 and 170 kb were identified as targets. These fragments were
      cloned, and subclones containing QpH1-homologous sequences were completely
      sequenced. The physical mapping of DNA fragments was achieved by PCR with primers
      derived from adjacent fragments, and a total of 18,360 bp was sequenced. Within
      the QpH1-homologous region spanning 16,624 bp, homology was as high as 99%.
      Deletions were identified within EcoRI fragments A(H)-C(H)-K(H)-B(H) (13,490 bp)
      and J(H)-G(H)-E(H)-L+-D(H) (6,509 bp) and in fragment A(H) alone (619 bp). An
      insertion of 744 bp was identified within the JDc region of Scurry Q217. A search
      for putative coding regions identified a total of 17 open reading frames (ORFs).
      Compared to plasmid QpH1, 6 ORFs were identical, 5 ORFs were different in size, 6
      ORFs were newly generated, and 25 ORFs were lost. It was found that plasmid
      homologous sequences in Scurry Q217 were of chromosomal origin.

PMID- 9150227
TI  - Rates of spontaneous mutation in an archaeon from geothermal environments.
AB  - To estimate the efficacy of mechanisms which may prevent or repair thermal damage
      to DNA in thermophilic archaea, a quantitative assay of forward mutation at
      extremely high temperature was developed for Sulfolobus acidocaldarius, based on
      the selection of pyrimidine-requiring mutants resistant to 5-fluoro-orotic acid.
      Maximum-likelihood analysis of spontaneous mutant distributions in wild-type
      cultures yielded maximal estimates of (2.8 +/- 0.7) x 10(-7) and (1.5 +/- 0.6) x
      10(-7) mutational events per cell per division cycle for the pyrE and pyrF loci,
      respectively. To our knowledge, these results provide the first accurate
      measurement of the genetic fidelity maintained by archaea that populate
      geothermal environments. The measured rates of forward mutation at the pyrE and
      pyrF loci in S. acidocaldarius are close to corresponding rates reported for
      protein-encoding genes of Escherichia coli. The normal rate of spontaneous
      mutation in E. coli at 37 degrees C is known to require the functioning of
      several enzyme systems that repair spontaneous damage in DNA. Our results provide
      indirect evidence that S. acidocaldarius has cellular mechanisms, as yet
      unidentified, which effectively compensate for the higher chemical instability of
      DNA at the temperatures and pHs that prevail within growing Sulfolobus cells.

PMID- 9150225
TI  - Two divergent catalase genes are differentially regulated during Aspergillus
      nidulans development and oxidative stress.
AB  - Catalases are ubiquitous hydrogen peroxide-detoxifying enzymes that are central
      to the cellular antioxidant response. Of two catalase activities detected in the
      fungus Aspergillus nidulans, the catA gene encodes the spore-specific catalase A
      (CatA). Here we characterize a second catalase gene, identified after probing a
      genomic library with catA, and demonstrate that it encodes catalase B. This gene,
      designated catB, predicts a 721-amino-acid polypeptide (CatB) showing 78%
      identity to an Aspergillus fumigatus catalase and 61% identity to Aspergillus
      niger CatR. Notably, similar levels of identity are found when comparing CatB to
      Escherichia coli catalase HPII (43%), A. nidulans CatA (40%), and the predicted
      peptide of a presumed catA homolog from A. fumigatus (38%). In contrast, the last
      two peptides share a 79% identity. The catalase B activity was barely detectable
      in asexual spores (conidia), disappeared after germination, and started to
      accumulate 10 h after spore inoculation, throughout growth and conidiation. The
      catB mRNA was absent from conidia, and its accumulation correlated with catalase
      activity, suggesting that catB expression is regulated at the transcription
      level. In contrast, the high CatA activity found in spores was lost gradually
      during germination and growth. In addition to its developmental regulation, CatB
      was induced by H2O2, heat shock, paraquat, or uric acid catabolism but not by
      osmotic stress. This pattern of regulation and the protective role against H2O2
      offered by CatA and CatB, at different stages of the A. nidulans life cycle,
      suggest that catalase gene redundancy performs the function of satisfying
      catalase demand at the two different stages of metabolic and genetic regulation
      represented by growing hyphae versus spores. Alternative H2O2 detoxification
      pathways in A. nidulans were indicated by the fact that catA/catB double mutants
      were able to grow in substrates whose catabolism generates H2O2.

PMID- 9150228
TI  - A [2Fe-2S] ferredoxin (FdVI) is essential for growth of the photosynthetic
      bacterium Rhodobacter capsulatus.
AB  - The physiological function of Rhodobacter capsulatus FdVI, a [2Fe-2S] ferredoxin,
      was investigated by the cloning, sequence analysis, and mutagenesis of its
      structural gene, called fdxE. The DNA region surrounding fdxE was mapped, and the
      nucleotide sequence of a 4.2-kb fragment was determined. fdxE is preceded by a
      sequence that is very similar to a sigma54 recognition site and is followed by a
      putative transcription stop signal, suggesting that fdxE forms a separate
      cistron. Two open reading frames were identified upstream and downstream of fdxE
      and were named ORFE0 and ORFE1, respectively. The former may encode a polypeptide
      having 34% similarity with HtrA, a serine protease found in enteric bacteria.
      ORFE1 is homologous to purU, a gene involved in purine biosynthesis. Interposon
      mutagenesis of fdxE was unsuccessful when attempted on the wild-type strain B10.
      Disruption of fdxE could be achieved only in strains harboring an additional copy
      of fdxE on a plasmid. Mutants obtained in this way and carrying a plasmid-borne
      copy of fdxE under the control of the nifH promoter grew only in N-free medium,
      thus demonstrating that fdxE expression is required for growth. Nevertheless,
      such mutants were found to spontaneously revert at a frequency of 5 x 10(-6) to
      an apparent wild-type phenotype, although they contained no detectable amount of
      FdVI. Taken together, the results indicate that FdVI is required for an essential
      metabolic function in R. capsulatus and that this FdVI dependence could be
      relieved by a single-mutation event. In accordance, FdVI biosynthesis was found
      to be constitutive in R. capsulatus.

PMID- 9150229
TI  - Identification and characterization of a basic cell surface-located protein from
      Lactobacillus fermentum BR11.
AB  - Extraction of Lactobacillus fermentum BR11 cells with 5 M LiCl yielded a
      preparation containing a single predominant polypeptide with an apparent
      molecular mass of 32 kDa. A clone encoding an immunoreactive 32-kDa polypeptide
      was isolated from a pUC18 library of L. fermentum BR11 DNA by screening with an
      antiserum raised against whole cells of L. fermentum BR11. Sequence determination
      of the insert in the clone revealed a complete 795-bp open reading frame (ORF)
      that defines a 28,625-Da polypeptide (BspA). N-terminal sequencing of the LiCl
      extracted polypeptide from L. fermentum BR11 confirmed that it is the same as the
      cloned BspA. BspA was found to have a sequence similar to those of family III of
      the bacterial solute-binding proteins. The sequences of two ORFs upstream of bspA
      are consistent with bspA being located in an operon encoding an ATP-binding
      cassette-type uptake system. Unusually, BspA contains no lipoprotein cleavage and
      attachment motif (LXXC), despite its origin in a gram-positive bacterium. Biotin
      labelling and trypsin digestion of whole cells indicated that this polypeptide is
      exposed on the cell surface. The isoelectric point as predicted from the putative
      mature sequence is 10.59. It was consequently hypothesized that the positively
      charged BspA is anchored by electrostatic interaction with acidic groups on the
      cell surface. It was shown that BspA could be selectively removed from the
      surface by extraction with an acidic buffer, thus supporting this hypothesis.

PMID- 9150230
TI  - A topological model for the general aromatic amino acid permease, AroP, of
      Escherichia coli.
AB  - The general aromatic amino acid permease, AroP, of Escherichia coli is
      responsible for the active transport of phenylalanine, tyrosine, and tryptophan.
      A proposed topological model for the AroP permease, consisting of 12 hydrophobic
      transmembrane spans connected by hydrophilic loops, is very similar to that of
      the closely related phenylalanine-specific permease. The validity of this model
      and its similarity to that of the PheP permease were investigated by studying
      fusion proteins of AroP permease and alkaline phosphatase. Based on the results
      obtained from the AroP-alkaline phosphatase sandwich fusions, we have
      significantly revised the proposed topological model for AroP in two regions. In
      this modified AroP topological model, the three charged residues E151, E153, and
      K160 are repositioned within the membrane in span 5. These three residues are
      conserved in a large family of amino acid transport proteins, and site-directed
      mutagenesis identifies them as being essential for transport activity. It is
      postulated that these residues together with E110 in transmembrane span 3 may be
      involved in a proton relay system.

PMID- 9150231
TI  - Cloning and characterization of the gene for amylosucrase from Neisseria
      polysaccharea: production of a linear alpha-1,4-glucan.
AB  - The gene for the amylosucrase from Neisseria polysaccharea (ATCC 43768) was
      cloned by use of a functional expression system in Escherichia coli XL1-Blue. The
      deduced amino acid sequence of the protein has homology to the sequences of the
      alpha-amylase class of enzymes, with the highest similarities being found to the
      sequences of the trehalose synthase from Pimelobacter sp. strain R48 (17) and
      amylomaltase from Thermotoga maritima (11). However, the regions of highest
      homology within the alpha-amylase class of enzymes, which are essential for the
      catalytic activity, are only scarcely found in the sequence of amylosucrase. By
      using the enzyme isolated from culture supernatants of transformed E. coli cells,
      it is possible to synthesize linear alpha-1,4-glucans from sucrose, indicating
      that the enzyme is not capable of producing alpha-1,6-glycosidic linkages on its
      own.

PMID- 9150232
TI  - Disappearance of the sigma E transcription factor from the forespore and the
      SpoIIE phosphatase from the mother cell contributes to establishment of cell
      specific gene expression during sporulation in Bacillus subtilis.
AB  - We used immunofluorescence microscopy to investigate mechanisms governing the
      establishment of cell-specific gene transcription during sporulation in the
      bacterium Bacillus subtilis. The transcription factors sigma E and sigma F are
      synthesized shortly after the start of sporulation but do not become active in
      directing gene transcription until after polar division, when the activity of
      sigma E is confined to the mother cell and the activity of sigma F is restricted
      to the forespore. We show that shortly after septation, sigma E and its
      proprotein precursor pro-sigma E appear to be absent from the forespore and that
      a null mutation in spoIIIE, a gene known to be required for the translocation of
      a chromosome into the forespore, allows sigma E and/or pro-sigma E to persist and
      sigma E to become active in the forespore. These findings suggest that the loss
      of sigma E/pro-sigma E from the forespore contributes to the compartmentalization
      of sigma E-directed gene transcription. We also investigated the distribution of
      SpoIIE, a regulatory phosphatase required for the activation of sigma F which
      exhibits a bipolar pattern of localization shortly after the start of
      sporulation. Normally, SpoIIE rapidly disappears from the sporangium, first from
      the mother-cell pole and then from the forespore pole. Here we show that a null
      mutation in spoIIIE causes the SpoIIE phosphatase to persist at both poles. The
      persistence of the SpoIIE phosphatase at the mother-cell pole could explain the
      lack of compartmentalization of sigma F activity observed in a spoIIIE null
      mutant. We conclude that the establishment of cell-specific gene transcription
      involves the loss of sigma E/pro-sigma E from the forespore and the loss of the
      SpoIIE phosphatase from the mother-cell pole and that both processes are
      dependent upon the SpoIIIE protein.

PMID- 9150233
TI  - A novel resistance mechanism against beta-lactams in Streptococcus pneumoniae
      involves CpoA, a putative glycosyltransferase.
AB  - Piperacillin resistance in Streptococcus pneumoniae was mediated by mutations in
      a novel gene, cpoA, that also confer transformation deficiency and a decrease in
      penicillin-binding protein la. cpoA is part of an operon located downstream of
      the primary sigma factor of S. pneumoniae. The deduced protein, CpoA, and the
      peptide encoded by the adjacent 3' open reading frame contained domains
      homologous to glycosyltransferases of procaryotes and eucaryotes that act on
      membrane-associated substrates, such as enzymes functioning in lipopolysaccharide
      core biosynthesis of gram-negative bacteria, RodD of Bacillus subtilis, which is
      involved in teichoic acid biosynthesis, and the human PIG-A protein, which is
      required for early steps of glycosylphosphatidylinositol anchor biosynthesis.
      This suggests that the cpo operon has a similar function related to cell surface
      components.

PMID- 9150234
TI  - Na+-induced structural change of a soil bacterium, S34, and Ca2+ requirement for
      preserving its original structure.
AB  - A drastic change in the outer membrane structure of a salt-sensitive soil
      bacterium, S34, related to the genus Deinococcus was induced by 0.2 to 0.4%
      (wt/vol) NaCl. The change was relieved by 6 mM CaCl2 and induced by 1 mM EGTA.
      The results indicate the strong dependence of the organism on calcium.

PMID- 9150235
TI  - Cloning and insertional inactivation of Streptomyces argillaceus genes involved
      in the earliest steps of biosynthesis of the sugar moieties of the antitumor
      polyketide mithramycin.
AB  - Two genes (mtmD and mtmE) were cloned and sequenced from the mithramycin producer
      Streptomyces argillaceus. Comparison with proteins in databases and enzymatic
      assays after expression in Escherichia coli showed that they encode a glucose-1
      phosphate:TTP thymidylyl transferase and a TDP-D-glucose 4,6-dehydratase,
      respectively. The mtmD gene was inactivated by gene replacement, generating a
      nonproducing mutant that accumulates a tetracyclic compound designated
      premithramycinone. The identification of premithramycinone reveals new aspects of
      the mithramycin biosynthetic pathway and suggests that at least some
      glycosylations occur before breakage of the fourth ring.

PMID- 9150236
TI  - Search for additional replication terminators in the Bacillus subtilis 168
      chromosome.
AB  - The Bacillus subtilis 168 chromosome is known to contain at least six DNA
      replication terminators in the terminus region of the chromosome. By using a
      degenerate DNA probe for the consensus terminator sequence and low-stringency
      hybridization conditions, several additional minor hybridizing bands were
      identified. DNA corresponding to the most intense of these bands was cloned and
      characterized. Although localized in the terminus region, it could not bind RTP
      and possibly represents a degenerate terminator. A search of the SubtiList
      database identified an additional terminator sequence in the terminus region,
      near glnA. It was shown to bind RTP and to function in blocking replication fork
      movement in a polar manner. Its orientation conformed to the replication fork
      trap arrangement of the other terminators. The low-stringency hybridization
      experiments failed to identify any terminus region-type terminators in the region
      of the chromosome where postinitiation control sequences (STer sites) are known
      to reside. The two most likely terminators in STer site regions, in terms of
      sequence similarity to terminus region terminators, were identified through
      sequence searching. They were synthesized and were found not to bind RTP under
      conditions that allowed binding to terminus region terminators. Neither did they
      elicit fork arrest, when present in a plasmid, under stringent conditions. It is
      concluded that the STer site terminators, at least the first two to the left of
      oriC, do not have the typical consensus A+B site makeup of terminus region
      terminators.

PMID- 9150237
TI  - Exchange of glutamate and gamma-aminobutyrate in a Lactobacillus strain.
AB  - Lactobacillus sp. strain E1 catalyzed the decarboxylation of glutamate (Glu),
      resulting in a nearly stoichiometric release of the products gamma-aminobutyrate
      (GABA) and CO2. This decarboxylation was associated with the net synthesis of
      ATP. ATP synthesis was inhibited almost completely by nigericin and about 70% by
      N,N'-dicyclohexylcarbodiimide (DCCD), without inhibition of the decarboxylation.
      These findings are consistent with the possibility that a proton motive force
      arises from the cytoplasmic proton consumption that accompanies glutamate
      decarboxylation and the electrogenic Glu/GABA antiporter and the possibility that
      this proton motive force is coupled with ATP synthesis by DCCD-sensitive ATPase.

PMID- 9150238
TI  - Antimonite is accumulated by the glycerol facilitator GlpF in Escherichia coli.
AB  - In a search for genes responsible for the accumulation of antimonite in
      Escherichia coli, TnphoA was used to create a pool of random insertional mutants,
      from which one antimonite-resistant mutant was isolated. Sequence analysis showed
      that the TnphoA insertion was located in the glpF gene, coding for the glycerol
      facilitator GlpF. The mutant was shown to be defective in polyol transport by
      GlpF. These results suggest that in solution Sb(III) is recognized as a polyol by
      the glycerol facilitator.

PMID- 9150239
TI  - Dechlorination of lindane by the cyanobacterium Anabaena sp. strain PCC7120
      depends on the function of the nir operon.
AB  - Nitrate is essential for lindane dechlorination by the cyanobacteria Anabaena sp.
      strain PCC7120 and Nostoc ellipsosporum, as it is for dechlorination of other
      organic compounds by heterotrophic microorganisms. Based on analyses of mutants
      and effects of environmental factors, we conclude that lindane dechlorination by
      Anabaena sp. requires a functional nir operon that encodes the enzymes for
      nitrate utilization.

PMID- 9150240
TI  - The Bacillus subtilis ureABC operon.
AB  - The Bacillus subtilis ureABC operon encodes homologs of the three subunits of
      urease enzymes of the family Enterobacteriaceae. Disruption of ureC prevented
      utilization of urea as a nitrogen source and resulted in a partial growth defect
      in minimal medium containing limiting amounts of arginine or allantoin as the
      sole nitrogen source.

PMID- 9150241
TI  - Purine biosynthesis in the domain Archaea without folates or modified folates.
AB  - The established pathway for the last two steps in purine biosynthesis, the
      conversion of 5-aminoimidazole-4-carboxamide ribonucleotide (ZMP) to IMP, is
      known to utilize 10-formyl-tetrahydrofolate as the required C1 donor cofactor.
      The biosynthetic conversion of ZMP to IMP in three members of the domain Archaea,
      Methanobacterium thermoautotrophicum deltaH, M. thermoautotrophicum Marburg, and
      Sulfolobus solfataricus, however, has been demonstrated to occur with only
      formate and ATP serving as cofactors. Thus, in these archaea, which use
      methanopterin (MPT) or another modified folate in place of folate as the C1
      carrier coenzyme, neither folate nor a modified folate serves as a cofactor for
      this biosynthetic transformation. It is concluded that archaea, which function
      with modified folates such as MPT, are able to carry out purine biosynthesis
      without the involvement of folates or modified folates.

PMID- 9150242
TI  - DNA sequencing and expression of the formyl coenzyme A transferase gene, frc,
      from Oxalobacter formigenes.
AB  - Oxalic acid, a highly toxic by-product of metabolism, is catabolized by a limited
      number of bacterial species utilizing an activation-decarboxylation reaction
      which yields formate and CO2. frc, the gene encoding formyl coenzyme A
      transferase, an enzyme which transfers a coenzyme A moiety to activate oxalic
      acid, was cloned from the bacterium Oxalobacter formigenes. DNA sequencing
      revealed a single open reading frame of 1,284 bp capable of encoding a 428-amino
      acid protein. A presumed promoter region and a rho-independent termination
      sequence suggest that this gene is part of a monocistronic operon. A PCR fragment
      containing the open reading frame, when overexpressed in Escherichia coli,
      produced a product exhibiting enzymatic activity similar to the purified native
      enzyme. With this, the two genes necessary for bacterial catabolism of oxalate,
      frc and oxc, have now been cloned, sequenced, and expressed.

PMID- 9150243
TI  - Effects of varying the type of saturated fatty acid in the rat diet upon serum
      lipid levels and spleen lymphocyte functions.
AB  - To obtain further information about the effects of specific dietary saturated
      fatty acids, weanling male rats were fed for 6 weeks on low fat (7.7% by weight)
      or high fat (17.8% by weight) diets which differed according to the principal
      fatty acids present. The diets were rich in caprylic and capric acids (medium
      chain triacylglycerols; MCT), lauric acid, palmitic acid at the sn-1(3) position,
      palmitic acid at the sn-2 position or stearic acid. The total proportions of
      saturated (42-46%), monounsaturated (36%), n-6 polyunsaturated (15%) and n-3
      polyunsaturated (2.2%) fatty acids were the same in all diets. Serum cholesterol
      concentrations were not different among rats fed the different diets, except that
      the concentration in the serum of rats fed the high fat diet with palmitic acid
      in the sn-2 position was high. This was reflected in higher HDL and LDL
      cholesterol concentrations in the serum of animals fed this diet. Triacylglycerol
      (TAG) concentrations tended to be higher in the serum of rats fed the low fat
      diets compared with those fed the high fat diets. They were lowest in the serum
      of MCT-fed rats irrespective of the level of fat in the diet and were highest in
      the serum of rats fed the low fat diet rich in stearic acid. These differences
      were due to lower chylomicron and VLDL TAG concentrations in the serum of MCT-fed
      rats and higher chylomicron and VLDL TAG concentrations in the serum of low fat,
      stearic acid-fed animals. The fatty acid compositions of the serum and of spleen
      lymphocytes were influenced by that of the diet fed. The ex vivo proliferation of
      lymphocytes from the spleens of rats fed the high fat diet rich in palmitic acid
      at the sn-2 position was greater than that of lymphocytes from animals fed the
      other diets. Natural killer (NK) cell activity tended to be lower for spleen
      lymphocytes from rats fed high fat diets than for those fed low fat diets
      irrespective of the principal saturated fatty acid present. NK cell activity was
      highest for spleen lymphocytes from animals fed the diets rich in palmitic acid
      and was lowest for those from animals fed the high fat diet rich in stearic acid.
      Spleen lymphocytes from the latter animals had the lowest proportion of CD16+
      cells, a marker for NK cells. Thus, this study shows that the type of saturated
      fatty acid present in the diet not only has subtle effects upon blood lipid and
      lipoprotein levels but can significantly affect lymphocyte functions. Spleen
      lymphocyte NK cell activity is decreased as the fat content of the diet
      increases. NK cell number and activity are reduced by a high fat diet rich in
      stearic acid. Spleen lymphocyte proliferation is enhanced by palmitic acid-rich
      diets, particularly if palmitic acid is in the sn-2 position of dietary TAG.

PMID- 9150244
TI  - Alterations in the structure of apolipoprotein B-100 determine the behaviour of
      LDL towards thromboplastin.
AB  - Apolipoprotein B-100 acts as an inhibitor of thromboplastin activity
      independently of the tissue factor pathway inhibitor (TFPI) associated with
      plasma lipoproteins. Analysis of the primary structure of Apo B-100 showed a
      higher than expected occurrence of lysine groups in the receptor-binding region.
      In order to demonstrate the participation of lysine groups of Apo B-100 in the
      inhibition of thromboplastin, thromboplastin and Apo B-100 were incubated
      together in the presence of poly-L-lysine, poly-L-arginine, lysine and arginine
      monomers. The inhibition of thromboplastin by Apo B-100 was completely suppressed
      in the presence of poly-L-lysine. Poly-L-arginine was found to be less effective
      and neither lysine or arginine monomers had any significant effect on the
      inhibitory effect of Apo B-100. Alterations in the structure of Apo B-100
      reconstituted in lipid vesicles resembling LDL, brought about by lipid
      peroxidation and lipid loading were examined by means of Fourier transform infra
      red spectroscopy. It was found that, upon oxidation without the addition of
      cupric ions, the apolipoprotein attains a more exposed conformation with an
      increase in alpha-helical structure. This increase occurred at the expense of
      beta-structure. On lipid loading, an increase in beta-structure at the expense of
      the alpha-helix, was demonstrated. It is therefore proposed that the variable
      action of LDL towards thromboplastin derives from alterations in the secondary
      structure of the Apo B-100, particularly the receptor-binding region.

PMID- 9150245
TI  - Regulation of the metabolism of plasma lipoproteins by apolipoprotein A-II.
AB  - Mouse apolipoprotein (apo) A-II has three variants (type A, B, and C) among
      inbred strains. To clarify the role of ApoA-II in the metabolism of high density
      lipoproteins (HDL), we constructed a new congenic mouse strain (P1.R1-Apoa2b)
      with type B ApoA-II of the SAMR1 strain on the genetic background of the SAMP1
      strain, and examined it together with another ApoA-II congenic strain (R1.P1
      Apoa2c) containing type C ApoA-II of the SAMPI strain on the SAMR1 strain and the
      parental SAMP1 and SAMR1 strains. Genetic characterization of the congenic
      strains indicated that only small regions surrounding the ApoA-II gene of the
      parental strains had been transferred. The strains with Apoa2c had lower plasma
      concentrations of HDL and ApoA-II, and a smaller HDL particle size than strains
      with Apoa2b. We detected no significant differences in the mRNA levels of ApoA-II
      or in the in vitro translational efficiency of the ApoA-II mRNA among the four
      strains. These findings suggested that the differences in the post-translational
      modification or efficiency of secretion between the Apoa2b and Apoa2c protein
      regulates the ApoA-II concentration which in turn determines the concentration
      and size of HDL in mice.

PMID- 9150246
TI  - Inhibition of proliferation of human smooth muscle cells by various HMG-CoA
      reductase inhibitors; comparison with other human cell types.
AB  - The effects of 6 HMG-CoA reductase inhibitors: pravastatin, lovastatin,
      simvastatin, atorvastatin, fluvastatin and cerivastatin were analyzed in cultured
      human smooth muscle cells, fibroblasts, endothelial cells and myoblasts. In
      vascular smooth muscle cells, pravastatin was a much weaker inhibitor of
      cholesterol synthesis than the 5 other drugs which displayed equally strong
      inhibitory potency. The anti-proliferative effects of these 6 drugs were analyzed
      by measuring cell number and mitochondrial dehydrogenase activity (MTT assay)
      after 3 days of incubation. IC25 values for inhibition of proliferation were very
      similar among the 4 cell types and were in the following order of magnitude:
      pravastatin << lovastatin = simvastatin = atorvastatin = fluvastatin <<
      cerivastatin. Only in the case of pravastatin was proliferation inhibited at
      lower concentration in smooth muscle cells than in the other cell types.
      Proliferation was also assessed by measuring DNA synthesis in these cells. A 3
      day-incubation with 1 microM of pravastatin had no effect on this parameter in
      all 4 cell types. However, 1 microM of simvastatin or lovastatin caused either an
      inhibition (in smooth muscle cells and endothelial cells) or stimulation (in
      fibroblasts) of this process. The effects of simvastatin on cell number,
      mitochondrial dehydrogenase activity and DNA synthesis were counteracted by
      simultaneous mevalonate addition. Simvastatin treatment was also associated with
      a change in the post-translational modification of the ras protein in smooth
      muscle cells, probably by inhibition of its farnesylation. Moreover, simvastatin
      treatment blocked the PDGF and bFGF-induced DNA synthesis in synchronized smooth
      muscle cells, whereas it does not affect the fetal calf serum-induced DNA
      synthesis in synchronized fibroblasts, suggesting that simvastatin blocks various
      steps of the cell cycle and that this effect depends on the cell type and the
      growth signalling pathway activated.

PMID- 9150247
TI  - Influence of bile salts on molecular interactions between sphingomyelin and
      cholesterol: relevance to bile formation and stability.
AB  - Bile salts enhance secretion of cholesterol into bile and its subsequent
      solubilization with phosphatidylcholine in mixed micelles. Sphingomyelin, a major
      structural lipid of the hepatocyte canalicular membrane, and disaturated
      phosphatidylcholines are known to impede nucleation of solid cholesterol crystals
      in supersaturated model systems. To understand these effects physico-chemically,
      we compared the influence of bile salts on interactions of cholesterol with
      natural sphingomyelins, as well as with dipalmitoyl and egg yolk
      phosphatidylcholines using various in vitro systems. Submicellar bile salts
      enhanced significantly bidirectional transfer of dehydroergosterol (a fluorescent
      cholesterol analog) between sphingomyelin and egg yolk phosphatidylcholine
      vesicles in the rank order taurocholate < tauroursodeoxycholate <
      taurodeoxycholate. Quasielastic light scattering of serially diluted
      sphingomyelin-taurocholate mixtures (1:1 molar ratio, 3 g/dl) revealed metastable
      temperature-dependent transitions between globular micelles, rod-shaped micelles
      and vesicles, suggesting that phase transitions under these experimental
      conditions were metastable only at temperatures below 37 degrees C. Ternary phase
      diagrams of all sphingomyelins and dipalmitoyl phosphatidylcholine with
      cholesterol and taurocholate (37 degrees C, 3 g/dl, 0.15 M NaCl) were identical.
      Compared to systems containing egg yolk phosphatidylcholine, the 1-phase micellar
      zone and 2- and 3-phase solid cholesterol crystal-containing zones were reduced
      markedly while the 2-phase zone with stable cholesterol-sphingomyelin liquid
      crystals was greatly expanded. Our results suggest that the high affinity of
      cholesterol for sphingomyelin is lost in the presence of bile salts. Our findings
      may be relevant to secretion of cholesterol into bile and to its inability to
      crystallize in the hepatocyte canalicular lumen or its surrounding membranes.

PMID- 9150248
TI  - Sterol carrier protein-2 mediated cholesterol esterification in transfected L
      cell fibroblasts.
AB  - The relative function of the 15 and 13.2 kDa forms of SCP-2 in cholesterol
      trafficking and metabolism was assessed using L-cell fibroblasts permanently
      transfected with the cDNA encoding for either the mouse 15 kDa or 13.2 kDa SCP-2.
      Expression of the 15 kDa, but not the 13.2 kDa SCP-2 increased [3H]cholesteryl
      ester formation from medium derived cholesterol by 30% compared to control cells.
      In both SCP-2 expressing cell lines, sphingomyelinase treatment increased the
      initial rate of [3 H]cholesteryl ester formation from plasma membrane derived
      cholesterol more than 11-fold and elevated [3H]cholesteryl ester levels 1.5-fold
      compared to control cells. Expression of both proteins resulted in nearly a 1.5
      fold increase in [3H]oleic acid esterification into cholesteryl esters, although
      [3H]oleic acid esterification into triacylglycerols was also increased in the
      13.2 kDa SCP-2 expressing cells relative to control. In both transfected cell
      lines, the cholesteryl ester mass was increased nearly 2-fold compared to control
      cells, consistent with increased cholesteryl ester synthesis. Similarly,
      triacylglycerol levels were increased 1.3-fold in the 13.2 kDa SCP-2 expressing
      cells which is consistent with the increased [3H]oleic acid esterification into
      triacylglycerol. In the 15 kDa SCP-2 expressing cells, triacylglycerol levels
      were decreased 60%, but free cholesterol levels were increased 1.2-fold relative
      to control cells. Thus, only the 15 kDa expression product, containing the
      putative targeting sequence, specifically enhanced cholesteryl ester formation
      from either plasma membrane or medium-derived cholesterol. In contrast, the 13.2
      kDa expression product, lacking the putative targeting sequence, stimulated an
      increase in [3H]oleic acid esterification into both cholesterol and
      triacylglycerol pools, suggesting a non-specific stimulation of fatty acid
      esterification.

PMID- 9150249
TI  - Micellar acceleration of oxygen-dependent reactions and its potential use in the
      study of human low density lipoprotein.
AB  - The reaction rate between superoxide and nitro-blue tetrazolium (NBT) is known to
      be accelerated/catalysed by micellar systems. Previous reports suggest that an
      accelerated rate of NBT reduction by micellar systems may be the result of either
      the binding of organic substrates such as NBT to the micellar phase giving a more
      favourable environment for superoxide reduction (an orientation effect), or the
      electrostatic interaction between micelles and superoxide. Here we show, using
      three different superoxide generating systems, that micelles composed of a number
      of different lipids or human low density lipoprotein (LDL) accelerates the
      apparent reaction between superoxide and NBT. Evidence in favour of an
      accelerated production of superoxide as opposed to the accelerated reduction of
      NBT is provided and we propose that the accelerated production of superoxide is a
      consequence of increased oxygen solubility in the lipid, rather than aqueous,
      phase. This is supported by: 1. The absence of any spectrophotometric changes due
      to interaction between lipid or LDL and reagents used. 2. The ability of micelles
      composed of a number of different fatty substances, including LDL, to accelerate
      superoxide generation, assessed by NBT reduction. 3. The behaviour of micelles,
      which appears to be one of substrate rather than catalyst, during the
      acceleration of NBT reduction. This is confirmed by the use of a known micellar
      catalyst, Triton-X100. This suggests that lipids contribute to the reaction as a
      substrate rather than a catalyst. 4. The inability of LDL to accelerate NBT
      reduction by potassium superoxide, a reaction which is independent of bimolecular
      oxygen. 5. The inability of LDL to accelerate NBT reduction when added after
      superoxide generation. 6. Studies that show LDL can enhance an NBT-independent
      monitor of oxidation, namely the transition metal-catalysed oxidation of vitamin
      C. 7. Estimations of the solubility of oxygen in LDL which appear to be
      consistent with reported physical measurements. Furthermore, we show that LDL
      modification can alter LDL-mediated micellar acceleration of superoxide
      generation. Extensive oxidation of LDL decreases micellar acceleration and
      minimal oxidation enhances it. We suggest that LDL micellar acceleration might
      serve as a novel approach to studying human LDL.

PMID- 9150250
TI  - Differential disposition of lysophosphatidylcholine in diabetes compared with
      raised glucose: implications for prostaglandin production in the diabetic kidney
      glomerulus in vivo.
AB  - An early increased formation of renal prostaglandins in diabetes which follows
      the hydrolysis of cellular phospholipids by cytosolic phospholipase A2 is of
      considerable importance in determining subsequent cellular function. As the
      disposition of concomitantly formed lysophosphatidylcholine may also affect
      cellular function, we investigated the cellular fate of exogenous
      lysophosphatidylcholine in mesangial cell-enriched glomerular cores and showed
      that in cells taken from diabetic rats there is an increased net reformation of
      phosphatidylcholine. Positional distribution of labelled palmitate from sn-1
      position palmitate-labelled lysophosphatidylcholine showed distribution to both
      sn-1 and sn-2 position of the phosphatidylcholine formed with a significantly
      increased sn-2 position labelling in diabetes. Although both a coenzyme A
      dependent acyltransferase activity and a coenzyme A-independent transacylase
      activity could be shown in these cells, the increased phosphatidylcholine
      formation in cells taken from diabetic animals was due to an increase in coenzyme
      A-independent transacylase activity. By contrast, an increase in coenzyme-A
      independent transacylase activity could not be demonstrated in cultured mesangial
      cells maintained with prolonged raised glucose concentrations. Cell homogenates
      possess the ability to transfer fatty acid from lysophosphatidylcholine to
      lysophosphatidylcholine and lysophosphatidylethanolamine with subsequent
      formation of phosphatidylcholine and phosphatidylethanolamine, respectively. In
      preparations from diabetic animals phosphatidylethanolamine formed in this manner
      was increased in the presence of an inhibitor of cytosolic phospholipase A2,
      indicating that it may provide a substrate for phospholipase A2 activity; an
      effect not seen in cultured cells maintained at raised glucose concentrations. It
      is concluded that one effect of an altered disposition of lysophosphatidylcholine
      in cells from diabetic animals would be to spare fatty acids released following
      phospholipase A2 hydrolysis of phospholipid, possibly providing the substrate for
      prostaglandin production, an effect not seen with raised glucose alone.

PMID- 9150251
TI  - The preferential mobilisation of C20 and C22 polyunsaturated fatty acids from the
      adipose tissue of the chick embryo: potential implications regarding the
      provision of essential fatty acids for neural development.
AB  - The aim of this study was to determine the relative mobilisation of the different
      fatty acyl components of the triacylglycerol (TAG) of the chick embryo's adipose
      tissue in the light of the specific requirements of the developing neural tissues
      of the embryo for C20-22 polyunsaturated fatty acids. Pieces of adipose tissue,
      obtained from embryos at various developmental stages, were incubated in vitro in
      Dulbecco's Medium containing serum albumen. The fatty acid compositions of the
      initial tissue TAG and of the free fatty acid (FFA) mobilised from the tissue
      during 1 h of incubation were determined and compared. The composition of the FFA
      released into the medium under conditions of basal (i.e., unstimulated) lipolysis
      was markedly different in several respects from that of the TAG from which it
      originated. The polyunsaturated fatty acids, 20:4n-6, 20:5n-3, 22:5n-3 and 22:6n
      3, were consistently found to be preferentially released into the medium, whereas
      the major fatty acyl constituents of the tissue, 16:0 and 18:1n-9, were
      selectively retained in the TAG. For example, at day 18 of development, the
      proportions (% w/w of fatty acids) of 20:5n-3 and 22:6n-3 released into the
      incubation medium were respectively 6.5 and 7.5 times higher than in the original
      tissue TAG. Glucagon stimulated the overall rate of mobilisation by approx. 2
      fold and also partially suppressed the preferential mobilisation of C20-22
      polyunsaturates. These results may be relevant to the elucidation of the means by
      which essential polyunsaturates are delivered from the yolk to the neural tissues
      of the embryo, with the implication of a mediatory role for the embryonic adipose
      tissue in this transfer.

PMID- 9150252
TI  - Contrasting adrenergic effects on lipoprotein lipase gene expression in the brown
      adipose tissue of intact mice and in cultured brown adipocytes from mice.
AB  - To examine the regulation of lipoprotein lipase (LPL) gene expression, LPL mRNA
      levels in the brown adipose tissue of intact mice and in mouse brown adipocyte
      cultures were examined. In intact mice, exposure to cold resulted in a rapid,
      transient, 5-fold increase in LPL mRNA level. Norepinephrine (NE) injection could
      fully mimic the effect of acute exposure to cold, and LPL mRNA and enzymatic
      activity were increased in parallel after NE injection. These results indicated
      positive adrenergic control of LPL gene expression in the brown adipose tissue of
      intact mice. In cultured mouse brown adipocytes, the level of spontaneously
      expressed LPL mRNA decreased in parallel with the progression of brown adipocyte
      differentiation. NE treatment of undifferentiated cells led to a decrease in LPL
      mRNA levels. In brown adipocytes that had reached a mature state, NE had a small
      negative or no effect on LPL mRNA levels, irrespective of whether the experiment
      was performed in the presence or absence of insulin or of newborn-calf serum. It
      was concluded that LPL gene expression in brown adipose tissue in intact mice is
      under adrenergic control but that this gene is not under positive adrenergic
      control in cultured brown adipocytes from mice, although these cells are
      otherwise adrenergically sensitive. The presence of additional factors may be
      necessary to confer adrenergic sensitivity to the LPL gene in the cultured brown
      adipocytes; alternatively, cells other than the mature brown adipocytes may
      confer the positive adrenergic sensitivity to the brown adipose tissue depots in
      situ.

PMID- 9150253
TI  - Occurrence and metabolism of anandamide and related acyl-ethanolamides in ovaries
      of the sea urchin Paracentrotus lividus.
AB  - Cannabinoid receptors have been described in sea urchin sperm and shown to
      mediate inhibition of sperm acrosome reaction. Anandamide (arachidonoyl
      ethanolamide), the mammalian physiological ligand at the cannabinoid CB1
      receptor, has been subsequently found to effect this inhibition. Here we present
      data showing that ovaries from the sea urchin Paracentrotus lividus contain
      anandamide and two related acyl-ethanolamides, as well as enzymatic activities
      potentially responsible for their biosynthesis and degradation. Pilot experiments
      carried out with either ovaries or spermatozoa, extracted from both P. lividus
      and Arbacea lixula and radiolabelled with [14C]ethanolamine, showed that in
      sexually mature ovaries of both species significant levels of radioactivity were
      incorporated into a lipid component with the same chromatographic behaviour as
      anandamide. Lipid extracts from P. lividus ovaries were purified and analysed by
      gas chromatography/mass spectrometry which showed the presence of low but
      measurable amounts of anandamide, palmitoyl- and stearoyl-ethanolamides. The
      extracts were also found to contain lipid components with the same
      chromatographic behaviour as the N-acyl-phosphatidyl-ethanolamines, the
      phospholipid precursors of acyl-ethanolamides in mammalian tissues, and capable
      of releasing anandamide, palmitoyl- and stearoyl-ethanolamides upon digestion
      with S. chromofuscus phospholipase D. Accordingly, whole homogenates from P.
      lividus contained an enzymatic activity capable of converting synthetic [3H]N
      arachidonoyl-phosphatidyl-ethanolamine into [3H]anandamide. Finally, mature
      ovaries of P. lividus were shown also to contain an amidohydrolase activity which
      catalyses the hydrolysis of anandamide and palmitoyl-ethanolamide to
      ethanolamine. This enzyme displayed subcellular distribution, pH/temperature
      dependency profiles and sensitivity to inhibitors similar but not identical to
      those of the previously described 'anandamide amidohydrolase' from mammalian
      tissues. These data support the hypothesis, formulated in previous studies, that
      anandamide or related metabolites may be oocyte-derived cannabimimetic regulators
      of sea urchin fertility.

PMID- 9150254
TI  - Dietary cholesterol and the activity of stearoyl CoA desaturase in rats: evidence
      for an indirect regulatory effect.
AB  - The effect of cholesterol on stearoyl CoA desaturase (SCD) was investigated.
      Previous work had shown that the addition of cholesterol to the diet of rats
      produced higher liver SCD activity compared to non-cholesterol-fed controls. We
      have confirmed this result and investigated the mechanism responsible for this
      cholesterol-induced higher SCD activity. Rats were fed either a 10% corn oil (CO)
      or a 10% corn oil/1% cholesterol (CO/CH) diet for 1, 3, or 7 days. SCD mRNA
      abundance was 3.3, 1.9, and 2.4 times greater in livers from CO/CH-fed animals
      after 1, 3, and 7 days, respectively. Northern hybridization of RNA from kidney,
      intestinal mucosa, heart, adipose, and liver demonstrated that cholesterol
      feeding specifically altered liver SCD mRNA. Liver esterified cholesterol content
      increased 27-fold with cholesterol feeding. This esterified cholesterol increase
      was accompanied by a proportionately greater increase in oleic acid compared to
      other fatty acids. These studies indicate that cholesterol does influence the
      expression of SCD specifically in the liver and suggest that the product, oleic
      acid, is preferentially esterified to cholesterol in the liver. Preliminary liver
      nuclear run-on assays from rats fed CO or CO/CH diets for 1 and 3 days indicate
      that transcription regulation is not a factor.

PMID- 9150255
TI  - Maize Activator transposase has a bipartite DNA binding domain that recognizes
      subterminal sequences and the terminal inverted repeats.
AB  - The mobility of maize transposable element Activator (Ac) is dependent on the 11
      bp terminal inverted repeats (IRs) and approximately 250 subterminal nucleotides
      at each end. These sequences flank the coding region for the transposase (TPase)
      protein, which is required for the transposition reaction. Here we show that Ac
      TPase has a bipartite DNA binding domain, and recognizes the IRs and subterminal
      sequences in the Ac ends. TPase binds cooperatively to repetitive ACG and TCG
      sequences, of which 25 copies are found in the 5' and 20 copies in the 3'
      subterminal regions. TPase affinity is highest when these sites are flanked on
      the 3' side by an additional G residue (A/TCGG), which is found at 75% of binding
      sites. Moreover, TPase binds specifically to the Ac IRs, albeit with much lower
      affinity. Two mutations within the IRs that immobilize Ac abolish TPase binding
      completely. The basic DNA binding domain of TPase is split into two subdomains.
      Binding to the subterminal motifs is accomplished by the C-terminal subdomain
      alone, whereas recognition of the IRs requires the N-terminal subdomain in
      addition. Furthermore, TPase is extremely flexible in DNA binding. Two direct or
      inverted binding sites are bound equally well, and sites that are five to twelve
      bases apart are similarly well bound. The consequences of these findings for the
      Ac transposition reaction are discussed.

PMID- 9150256
TI  - Regulatory elements in the promoter of the vitelline membrane gene VM32E of
      Drosophila melanogaster direct gene expression in distinct domains of the
      follicular epithelium.
AB  - The Drosophila vitelline membrane protein gene VM32E is expressed according to a
      precise temporal and spatial program in the follicle cells. Results from germ
      line transformation experiments using different fragments of the -465/-39 VM32E
      region fused to the hsp/lacZ reporter gene revealed that the region -348/-39 is
      sufficient to confer the wild-type expression pattern. Within this segment,
      distinct cis-regulatory elements control VM32E expression in ventral and dorsal
      follicle cells. The region between -135/-113 is essential for expression of the
      VM32E gene in the ventral columnar follicle cells. Expression in the dorsal
      domain requires the two regions -348/-254 and -118/-39. Furthermore, the region 
      253/-119 appears to contain a negative element that represses gene activity in
      anterior centripetal cells. We suggest that the expression of the VM32E gene
      throughout the follicular epithelium is controlled by specific cis-regulatory
      elements acting in distinct spatial domains and following a precise developmental
      program.

PMID- 9150257
TI  - A novel fission yeast gene, kms1+, is required for the formation of meiotic
      prophase-specific nuclear architecture.
AB  - In the meiotic prophase nucleus of the fission yeast Schizosaccharomyces pombe,
      chromosomes are arranged in an oriented manner: telomeres cluster in close
      proximity to the spindle pole body (SPB), while centromeres form another cluster
      at some distance from the SPB. We have isolated a mutant, kms1, in which the
      structure of the meiotic prophase nucleus appears to be distorted. Using specific
      probes to localize the SPB and telomeres, multiple signals were observed in the
      mutant nuclei, in contrast to the case in wild-type. Genetic analysis showed that
      in the mutant, meiotic recombination frequency was reduced to about one-quarter
      of the wild-type level and meiotic segregation was impaired. This phenotype
      strongly suggests that the telomere-led rearrangement of chromosomal distribution
      that normally occurs in the fission yeast meiotic nucleus is an important
      prerequisite for the efficient pairing of homologous chromosomes. The kms1 mutant
      was also impaired in karyogamy, suggesting that the kms1+ gene is involved in SPB
      function. However, the kms1+ gene is dispensable for mitotic growth. The
      predicted amino acid sequence of the gene product shows no significant similarity
      to known proteins.

PMID- 9150258
TI  - A novel cytoplasmic structure containing DNA networks in Entamoeba histolytica
      trophozoites.
AB  - We report here the presence of cytoplasmic DNA arranged in networks in the
      trophozoites of the human parasite Entamoeba histolytica. Cytoplasmic DNA was
      detected in live trophozoites in a structure that we called EhkO, using the
      fluorescent dye acridine orange, and by in situ hybridization to trophozoites
      with a rDNA probe. The EhkO was found in the axenically grown clones A, L6
      (strain HMI:IMSS) and MAVax (strain MAV) and in the polyxenically grown clone
      MAVpx (strain MAV). Bacteria present in MAVpx did not cross hybridize with the
      DNA probe neither in in situ hybridization or in Southern blot experiments.
      Autoradiography of metabolically [3H]thymidine-labeled trophozoites showed the
      presence of EhkO, and an EhkO-enriched fraction, purified from a nuclei-free
      extract and examined by light microscopy, exhibited [3H]thymidine incorporation
      into this structure. DNA was purified from the EhkO and enriched nuclear
      fractions and analyzed by transmission electron microscopy. The EhkO fraction
      contained DNA networks resembling those of trypanosome kDNA, whereas nuclear DNA
      was present mainly as linear molecules and some circles. Our findings imply that
      E. histolytica may be taxonomically more closely related to the Trypanosomatidae
      than previously suspected.

PMID- 9150259
TI  - Identification of a new cis-regulatory element in a Nicotiana tabacum
      polyubiquitin gene promoter.
AB  - The polyubiquitin gene Ubi.U4 is expressed in a complex pattern during cell
      division and plant development in Nicotiana tabacum. Plants transformed with the
      uidA reporter gene placed under the control of the proximal 263 bp of the
      promoter are able to express GUS activity in dividing cells. This expression is
      modified when a G-box-like motif is mutated. In order to clarify the
      transcriptional regulation of this gene, we analysed positively regulating
      sequences in this proximal promoter by electrophoretic mobility-shift assays
      (EMSA). We observed that the G-box-like element gave rise to only weak protein
      DNA bands but that a new motif, GCTGTAC, directs formation of numerous,
      distinctive, strong and developmentally specific shifts with nuclear extracts
      prepared from various different developmental stages and from dividing cells.
      Point mutations within this motif abolish formation of the protein-DNA complexes
      and reduce promoter activity in transient expression assays. This novel putative
      cis-acting element, which we called the U-box, present 12 nucleotides upstream of
      the G-box-like element, thus seems also to be critical for Ubi.U4 promoter
      activity.

PMID- 9150260
TI  - Screening and identification of yeast sequences that cause growth inhibition when
      overexpressed.
AB  - To isolate genes that negatively regulate cell growth, we constructed a galactose
      inducible expression library with partially digested Saccharomyces cerevisiae
      genomic DNA fragments inserted downstream of the GAL10 promoter. In all, 240,000
      yeast transformants were screened for lethality on galactose medium. From 17 such
      transformants identified, 16 nonoverlapping DNA sequences were obtained.
      Restriction mapping and determination of DNA sequences adjacent to the GAL10
      promoter indicated that the inserts encoded part or all of the URA2, RBP1, TPK3,
      SAC7, BOI1, and BNI1 genes, and also open reading frames (ORFs) from chromosomes
      IV, V, IX, XI, and XIII. Some of the identified sequences lacked the amino
      terminal sequences of the ORFs, suggesting that truncated forms of the proteins
      might be necessary for growth inhibition. The sequence of the pGA108 insert was
      highly homologous to the telomeric X-element and contained an ARS consensus
      sequence, suggesting a possible growth inhibitory effect of an RNA molecule.
      Overexpression of the BNI1 deltaN and BOI1 deltaN genes, which lacked amino
      terminal sequences, was associated with phenotypes similar to those of mutants
      defective in bud formation. Overexpression of the GIN4 and GIN12 sequences
      induced elongated buds and a G2/M arrest-like phenotype, respectively. The
      phenotypes induced by the overexpression of our cloned sequences could result
      from either a dominant-positive or a dominant-negative effect and, unexpectedly,
      in one case from an effect of an RNA.

PMID- 9150261
TI  - Cycloheximide induces a subset of low temperature-inducible genes in maize.
AB  - To investigate further the signal transduction pathway that mediates the cold
      stress response in maize, we isolated a low temperature-inducible cDNA clone
      (ZmCDPK1) that encodes a calcium-dependent protein kinase. Time-course
      experiments revealed that the low-temperature induction of ZmCDPK1 precedes that
      of mlip15, another cold-inducible gene that codes for a DNA-binding protein of
      the basic region/leucine zipper (bZIP) type, indicating that ZmCDPK1 might be
      located upstream of mlip15 in the cold-stress signal transduction pathway. We
      observed that the steady-state mRNA level of mlip15 drastically increased after
      cycloheximide treatment. In addition to mlip15, cycloheximide elevates the
      transcript levels of two other low temperature-induced genes, ZmCDPK1, and Adh1,
      which encodes alcohol dehydrogenase 1. In contrast, the chalcone synthase gene
      was only inducible by low temperature. The accumulation of the mlip15 transcript
      at low temperatures and in response to cycloheximide was significantly reduced by
      pretreatment with a calcium chelator, suggesting that calcium is involved in both
      cases of mlip15 induction. The signal transduction pathways triggered by low
      temperature and cycloheximide are discussed in relation to these observations.

PMID- 9150262
TI  - Transcription elongation factor S-II is not required for transcription-coupled
      repair in yeast.
AB  - Two different subpathways play a role in removal of UV-induced cyclobutane
      pyrimidine dimers (CPDs) by nucleotide excision repair (NER). The relatively slow
      global genome repair subpathway operates on all CPDs irrespective of their
      position in the DNA, whereas the transcription-coupled repair subpathway is
      responsible for the rapid removal of CPDs from transcribed strands. In
      Saccharomyces cerevisiae, the RAD26 gene is implicated in transcription-coupled
      repair. However, transcription-coupled repair is not completely absent in rad26
      mutants, and therefore other gene products are possibly involved in this
      subpathway. Based on in vitro experiments with purified components, the
      transcription elongation factor S-II appeared to be a candidate for a function in
      transcription-coupled repair. To investigate a possible role of S-II in
      transcription-coupled repair in vivo in yeast, S-II null mutations were
      introduced into various genetic backgrounds differing in NER capacity. UV
      sensitivity was not altered by disruption of the S-II gene in a RAD+ (NER
      proficient) strain, or in rad26 (impaired in efficient transcription-coupled
      repair), rad7 (lacking global genome repair), or rad7 rad26 (lacking global
      genome repair, but having residual transcription-coupled repair capacity)
      mutants. Moreover, S-II did not influence the repair rate on the transcribed
      strand of the RPB2 gene, either in repair-proficient or in rad7 rad26
      backgrounds. Hence, transcription-coupled repair is fully functional in yeast
      cells lacking the gene encoding S-II. Furthermore, S-II is not required for the
      Rad26-independent residual transcription-coupled repair in vivo.

PMID- 9150263
TI  - Introns boost transgene expression in Drosophila melanogaster.
AB  - Using Drosophila as a host, we have examined the effect that the presence of an
      intron has on the accumulation of a processed transgene mRNA. To provide a model
      system that was free from major position effects, two fish antifreeze protein
      (AFP) transgenes were arranged in divergent transcriptional orientation from a
      central Drosophila yolk protein promoter/enhancer region and introduced into the
      flies by P-element transformation and/or mobilization. In this way the
      organization of both the structural genes and the promoter elements mimicked
      their natural arrangements. When one member of the fish AFP transgene pair had
      its single 180 bp intron deleted, there was a 2- to 11-fold (average 5-fold)
      decrease in its mRNA level compared to that generated from the control gene
      containing the fish AFP intervening sequence. When the deleted intron was
      replaced by a 70 bp intervening sequence originating from the yolk protein 1
      gene, mRNA accumulation was restored to its original level. Even for the
      streamlined genome of Drosophila, where the intron number and size are generally
      reduced compared to mammals, the presence of an intervening sequence appears to
      facilitate mRNA accumulation.

PMID- 9150264
TI  - Identification of transposon-like elements in non-coding regions of tomato ACC
      oxidase genes.
AB  - 1-aminocyclopropane-1-carboxylate (ACC) oxidase, which catalyses the terminal
      step in ethylene biosynthesis, is encoded by a small multigene family in tomato
      that is differentially expressed in response to developmental and environmental
      cues. In this study we report the isolation and sequencing of approximately 2 kb
      of 5'-flanking sequence of three tomato ACC oxidase genes (LEACO1, LEACO2,
      LEACO3) and the occurrence of class I and class II mobile element-like insertions
      in promoter and intron regions of two of them. The LEA CO1 upstream region
      contains a 420-bp direct repeat which is present in multiple copies in the tomato
      genome and is very similar to sequences in the promoters of the tomato E4 and
      2A11 genes. The region covering the repeats resembles the remnant of a
      retrotransposon. Two copies of a small transposable element, belonging to the
      Stowaway inverted repeat element family, have been found in the 5'-flanking
      sequence and the third intron of LEACO3.

PMID- 9150265
TI  - Impaired lysogenisation of the Escherichia coli rpoA341 mutant by bacteriophage
      lambda is due to the inability of CII to act as a transcriptional activator.
AB  - The C-terminus of the alpha subunit of Escherichia coli RNA polymerase is known
      to function in transcriptional activation at certain promoters. This region was
      previously shown to be necessary for full activation of the pE promoter by the
      phage lambda CII protein in vitro. In this work we investigated the inability of
      phage lambda to follow the lysogenic pathway in cells carrying the point mutation
      rpoA341 (a change of lysine 271 to glutamic acid). We found that neither
      overexpression of the cII gene nor stabilisation of the CII protein by the can1
      mutation or by cIII gene overexpression was able to suppress the block in
      lysogenisation. In contrast, the lambda cin1 phage, which carries a CII
      independent promoter for the expression of the cI gene, was able to efficiently
      lysogenise the rpoA341 mutant strain. Furthermore, the rpoA341 mutation prevented
      the activation of pE-lacZ and pI-lacZ transcriptional fusions by CII. Therefore
      we conclude that transcriptional activation by the cII gene product is abolished
      by the rpoA341 mutation, most probably due to impaired interaction between the
      CII activator and mutant RNA polymerase. The inability of RNA polymerase to
      respond to CII results in the impairment of lysogenisation of the rpoA341 mutant
      by phage lambda.

PMID- 9150266
TI  - Secretion of the lantibiotics epidermin and gallidermin: sequence analysis of the
      genes gdmT and gdmH, their influence on epidermin production and their regulation
      by EpiQ.
AB  - The closely related lantibiotics epidermin and gallidermin are produced by
      Staphylococcus epidermidis Tu3298 and S. gallinarum Tu3928, respectively. The
      epidermin biosynthetic genes involved in maturation, regulation, and immunity
      have been identified previously. How epidermin or gallidermin is secreted,
      however, has remained unclear. Here, we characterize two additional genes, epiH
      and epiT, as well as the homologous gallidermin genes gdmH and gdmT. EpiT and
      GdmT are similar to one-component ABC transporters that are involved in the
      secretion of proteins or peptides. EpiH and GdmH are hydrophobic proteins without
      conspicuous similarities to other proteins. Comparison of the gene sequences
      revealed that epiT is incomplete, having an internal deletion that causes a frame
      shift and a second deletion at the 3'-end, while gdmT is intact. Introduction of
      epiT and epiH into the heterologous host S. carnosus (pTepi14) bearing the
      maturation and regulation genes had no significant effect on the rather low level
      of epidermin production. The presence of the homologous gdmT and gdmH, however,
      resulted in a strong increase (seven- to tenfold) in the production level, which
      is very likely to be due to increased efficiency of epidermin secretion. Both
      gdmT and gdmH were necessary for this effect, indicating that the two gene
      products cooperate in some way. In the epidermin-producing wild-type strain
      Tu3298, which contains epiH and the disrupted epiT, the addition of gdmT alone
      led to a two-fold increase in epidermin production. Both gdmT and gdmH and the
      corresponding epi genes were activated by the transcriptional regulator EpiQ;
      this is in accordance with the presence of putative EpiQ operator sites in the
      promoter regions.

PMID- 9150267
TI  - The RecB protein of Escherichia coli translocates along single-stranded DNA in
      the 3' to 5' direction: a proposed ratchet mechanism.
AB  - To investigate the role that the individual subunits play in the ATP-dependent
      helicase activity of the RecBCD protein we have investigated the ability of the
      RecB, RecC and RecD proteins to displace various 20-mer oligonucleotides annealed
      to either end or to the centre of an oligonucleotide 60 bases long. The results
      show that the only subunit which can displace the 20-mers in the absence of the
      other subunits is the RecB protein. Moreover, the 20-mer is displaced only if it
      is annealed to the 60-mer at the 5' end or the middle, suggesting that the RecB
      protein translocates along the 60-mer in the 3' to 5' direction, displacing
      annealed 20-mers as it proceeds. We have shown that reconstituted RecBC and
      RecBCD complexes displace the 20-mers but, unlike RecB, they do not require a 3'
      ended single-stranded region for helicase action, but can displace the 20-mers
      from either end of the 60-mer. The level of helicase activity of the RecBC
      complex is considerably greater than that of RecB alone, and the activity of the
      RecBCD complex appears to be greater still. This hierarchy of activity is also
      shown by DNA binding studies, but is not reflected in the ATPase activities of
      the enzymes. We have also shown that the ability of trypsin to cleave various
      sites on the RecB molecule is modified by the presence of ATP or ATP-gamma-S,
      suggesting that conformational changes may be induced in RecB upon ATP binding.
      We discuss a model for the ATP-driven, unidirectional motion of the RecB
      translocase along single-stranded DNA. In this model, the RecB molecule binds to
      single-stranded DNA and then translocates along it, one base at a time, in the 3'
      to 5' direction, by a 'ratchet' mechanism in which repeated stretching and
      contraction of the protein is coupled to ATP hydrolysis. The RecC protein in the
      RecBC complex is proposed to act as a 'sliding clamp' which increases
      processivity by preventing dissociation.

PMID- 9150268
TI  - Development of AFLP markers in barley.
AB  - To investigate the application of amplified fragment length polymorphism (AFLP)
      markers in barley, 96 primer combinations were used to generate AFLP patterns
      with two barley lines, L94 and Vada. With seven primer combinations, only a few
      intense bands were obtained, probably derived from repeated sequences. With the
      majority of the remaining 89 primer combinations, on average about 120
      amplification products were generated, and the polymorphism rate between the two
      lines was generally over 18%. Based on the number of amplified products and the
      polymorphism rate, the 48 best primer combinations were selected and tested on 16
      barley lines, again including L94 and Vada. Using a subset of 24 primer
      combinations 2188 clearly visible bands within the range from 80 to 510 bp were
      generated; 55% of these showed some degree of polymorphism among the 16 lines.
      L94 versus Vada showed the highest polymorphism rate (29%) and Proctor versus
      Nudinka yielded the lowest (12%). The polymorphism rates per primer combination
      showed little dependence on the barley lines used. Hence the most efficient and
      informative primer combinations identified for a given pair of lines turned out
      to be highly efficient when applied to others. Generally, more than 100 common
      markers (possibly locus specific) among populations or crosses were easily
      identified by comparing 48 AFLP profiles of the parent lines. The existence of
      such a large number of markers common to populations will facilitate the merging
      of molecular marker data and other genetic data into one integrated genetic map
      of barley.

PMID- 9150269
TI  - Wound-inducible and organ-specific expression of ORF13 from Agrobacterium
      rhizogenes 8196 T-DNA in transgenic tobacco plants.
AB  - Tissue-specific expression of the ORF13 promoter from Agrobacterium rhizogenes
      8196 was assessed throughout the development of transgenic tobacco plants using a
      GUS reporter gene. ORF13 exhibited high activity in roots but with different
      patterns of expression. The activity of the ORF13 promoter in vascular tissues
      increased from the base to the tip of the stem. The ORF13 promoter is wound
      inducible in a limited area adjacent to the wound site. The time course of wound
      induction of ORF13 in transgenic tobacco containing an ORF13 promoter-GUS
      translational fusion was similar to that previously described for genes involved
      in plant defense responses. A series of 5' deletions of the ORF13 promoter fused
      to the beta-glucuronidase gene was examined for expression in roots and leaves of
      transgenic plants. Cis-acting elements that modulate quantitative expression of
      the transgene after wounding were detected.

PMID- 9150270
TI  - Inhibitors of actin polymerization and calmodulin binding enhance protein kinase
      C-induced translocation of MARCKS in C6 glioma cells.
AB  - MARCKS (myristoylated alanine-rich C-kinase substrate) is known to interact with
      calmodulin, actin filaments, and anionic phospholipids at a central basic domain
      which is also the site of phosphorylation by protein kinase C (PKC). In the
      present study, cytochalasin D (CD) and calmodulin antagonists were used to
      examine the influence of F-actin and calmodulin on membrane interaction of MARCKS
      in C6 glioma cells. CD treatment for 1 h disrupted F-actin filaments, increased
      membrane bound immunoreactive MARCKS (from 51% to 62% of total), yet markedly
      enhanced the amount of MARCKS translocated to the cytosolic fraction in response
      to the phorbol ester 4beta-12-O-tetradecanoylphorbol 13-acetate. In contrast, CD
      treatment had no effect on phorbol ester-stimulated phosphorylation of MARCKS or
      on translocation of PKC alpha to the membrane fraction. Staurosporine also
      increased membrane association of MARCKS in a PKC-independent manner, as no
      change in MARCKS phosphorylation was noted and bis-indolylmaleimide (a more
      specific PKC inhibitor) did not alter MARCKS distribution. Staurosporine
      inhibited the phorbol ester-induced translocation of MARCKS but not of PKC alpha
      in both CD pretreated and untreated cells. Calmodulin antagonists
      (trifluoperazine, calmidazolium) had little effect on the cellular distribution
      or phosphorylation of MARCKS, but were synergistic with phorbol ester in
      translocating MARCKS from the membrane without a further increase in its
      phosphorylation. We conclude that cytoskeletal integrity is not required for
      phosphorylation and translocation of MARCKS in response to activated PKC, but
      that interaction with both F-actin and calmodulin might serve to independently
      modulate PKC-regulated localization and function of MARCKS at cellular membranes.

PMID- 9150271
TI  - Nitric oxide synthase and arginase in cells isolated from the rat gastric mucosa.
AB  - Nitric oxide (NO) synthase activity, which converts arginine to citrulline and
      NO, is present in homogenates of rat gastric mucosal cells. The aims of this
      study were to identify the form of NO synthase expressed in gastric cells
      isolated from fed rats, and to investigate the metabolism of arginine by
      suspensions of intact mucosal cells. Antibodies directed against the neuronal
      form of NO synthase recognised a protein of 160 kDa on immunoblots of extracts of
      gastric cells, and stained isolated cells of approx. 8 microm in diameter. NO
      synthase was enriched in a cell fraction which banded at high-density in a
      Percoll gradient, and was inhibited (IC50) by N(G)-nitro-L-arginine (0.8 microM),
      N(G)-monomethyl-L-arginine (12.6 microM), L-canavanine (147 microM),
      trifluoperazine (140 microM) and by phosphorylation involving protein kinase C.
      Intact gastric cells converted exogenous arginine to ornithine and citrulline.
      Arginase was present in the cells, and was predominantly responsible for arginine
      metabolism because formation of ornithine and citrulline was reduced by the
      arginase inhibitors, N(G)-hydroxy-L-arginine and L-ornithine, but not by NO
      synthase inhibitors such as N(G)-nitro-L-arginine. In conclusion, NO synthase
      that resembles the neuronal isoform is present in gastric mucosal cells, but a
      pathway involving arginase seems to be largely responsible for citrulline
      formation from exogenous arginine in intact mucosal cells.

PMID- 9150272
TI  - Electrogenic ion transport in the mouse endometrium: functional aspects of the
      cultured epithelium.
AB  - A primary culture of mouse endometrial epithelium grown on permeable supports was
      established and the electrogenic ion transport across the endometrial epithelium
      was studied using the short-circuit current (I(SC)) technique. Enzymatically
      isolated mouse endometrial cells were immunostained with epithelial cells
      markers, cytokeratins, indicating an epithelial origin of the culture. Mouse
      endometrial epithelial cells grown on Millipore filters formed polarized
      monolayers with junctional complexes as revealed by light and electron
      microscopy. The cultured monolayers exhibited an average basal I(SC) of 4.6 +/-
      0.3 microA/cm2, transepithelial voltage of 2.7 +/- 0.2 mV and transepithelial
      resistance of 599 +/- 30 omega cm2. The basal current was reduced by 85% in Na+
      free solution and 13% in Cl(-)-free solution. The basal current could also be
      substantially (57.7%) blocked by an apical Na+ channel blocker, amiloride (10
      microM), suggesting that Na+ absorption largely contributed to the basal current.
      Apical addition of Cl- channel blocker, DPC (2 mM), also exhibited an inhibitory
      effect, 19.4%, on the basal I(SC), indicating minor involvement of Cl- secretion
      as compared to that of Na+ absorption. The cultured endometrial epithelium also
      responded to a number of secretagogues including adrenaline and forskolin with
      increases in the I(SC), which could involve substantial Cl- secretion. The
      present study has established a culture of mouse endometrial epithelium
      exhibiting predominantly Na+ absorption under unstimulated condition, and Cl-
      secretion in response to various secretagogues. This culture may be useful for
      studying various regulatory mechanisms of electrogenic ion transport across the
      endometrial epithelium.

PMID- 9150274
TI  - Role of prostaglandin E2 in regulation of low and high water osmotic permeability
      in frog urinary bladder.
AB  - The water osmotic permeability of frog urinary bladder was found to be increased
      from 0.08 +/- 0.01 to 1.28 +/- 0.20 microl/min cm2 when serosal bathing medium
      was changed 4 times for a fresh Ringer solution. High epithelium permeability is
      accompanied by an increased content of cyclic AMP in the bladder tissue (by 42%,
      P < 0.01), higher activity of both basal and forskolin-stimulated membrane
      adenylate cyclase (AC) (by 109% and 74%, respectively, P < 0.05) and by
      appearance of aggregates of intramembranous particles in the apical membrane. The
      water flow was inhibited by 10(-9)-10(-5) M prostaglandin E2 (PGE2); the
      inhibitory effect was eliminated in the presence of 10(-4) M N-ethylmaleimide.
      The increase of water permeability due to changes of the bathing medium was
      accompanied by a decrease of serosal PGE2 concentration from 14.8 +/- 1.0 in the
      1st solution to 0.6 +/- 0.1 nM in the 5th. 10(-6) M PGE2 in vitro inhibited the
      activity of membrane AC from highly permeable bladders by 33.4% (P < 0.02).
      Pretreatment of the membranes with 10 microg/ml pertussis toxin (PT) completely
      reversed this effect (+149%, P < 0.01). A significant activation of AC was also
      observed under 10(-10) M PGE2 (by 196%). These data demonstrate that the water
      permeability could be markedly increased independently of ADH, suggesting that
      the trigger role in activation of water transport is played by a decreased level
      of PGE2 which could stimulate AC.

PMID- 9150275
TI  - Overproduction of urokinase-type plasminogen activator is regulated by
      phospholipase D- and protein kinase C-dependent pathways in murine mammary
      adenocarcinoma cells.
AB  - Urokinase-type plasminogen activator (uPA) initiates a proteolytic cascade with
      which invasive cells eliminate barriers to movement. The signaling pathways
      regulating uPA production in tumor cells remain unclear. We first studied the
      effects of n-butanol, a phospholipase D (PLD) and protein kinase C (PKC)
      inhibitor, on the production of uPA in murine mammary adenocarcinoma cells. Tumor
      cell monolayers treated during 24 h with 0.3% v/v n-butanol, secreted 45-50% less
      uPA to the culture medium than control monolayers (P < 0.001) as determined by
      radial caseinolysis, zymography and western blot. This inhibition occurred also
      with 5-h treatments and remained up to 5 h after the removal of the alcohol.
      Treatment with the phorbol ester PMA or with EGF, strongly increased uPA
      production (P < 0.001). Interestingly, a mild inhibition of uPA production was
      observed when PMA stimulation was assayed in cotreatments with n-butanol. In
      contrast EGF was unable to reverse the inhibition induced by n-butanol. H7
      significantly inhibited uPA activity (P < 0.001) secreted to the culture media.
      Furthermore, phosphatidic acid significantly stimulated uPA production meanwhile
      propranolol, which blocks phosphatidic acid availability, reduced it, suggesting
      a main regulatory role for this intermediary metabolite. These results suggest
      for the first time that uPA production is regulated by PLD and PKC signal
      transduction pathways in murine mammary adenocarcinoma cells.

PMID- 9150273
TI  - Differential expression of proteins regulating cell cycle progression in growth
      vs. differentiation.
AB  - The level of various G1 cyclins and cyclin-dependent kinases (cdks) present in
      the nuclei of synchronized ML-1 human myeloblastic leukemia cells was determined
      as a function of time after initiation of cell growth with insulin-like growth
      factor-1 (IGF-1) and transferrin (Tf), and following induction of differentiation
      with transforming growth factor-beta1 (TGF-beta1). Cyclin E and cdk2 were
      expressed at relatively high levels in the nuclei of proliferation-stimulated
      cells, whereas cyclin D1 and cdk5 were expressed at comparably high levels in the
      nuclei of differentiation-induced cells. In the nuclear extracts from
      proliferation-stimulated cells, cyclin E complexed specifically with cdk2,
      whereas in nuclear extracts from differentiation-induced cells, cyclin D1 bound
      specifically to cdk5. Increased cyclin E/cdk2 expression was accompanied by
      increased DNA synthesis, whereas increased cyclin D1/cdk5 levels correlated with
      decreased DNA synthesis. In both growth- and differentiation-induced cells,
      cyclin D2 expression preceded the expression of cyclin D3, and a significantly
      larger amount of these cyclins was present in differentiation- as compared to
      proliferation-induced cells. In contrast, cdk4 and cdk6 were present at similar
      levels in the nuclear extracts from both growth- and differentiation-induced
      cells. These data show that, in ML-1 cells, the proliferation-associated
      progression from G1 to S, as well as the differentiation-associated transit from
      G1 to maturation is accompanied by the expression of specific cyclin/cdk pairs,
      comprising cdk2/cyclin E in growth and cdk5/cyclin D1 in differentiation.

PMID- 9150276
TI  - Cationic liposome-mediated expression of HIV-regulated luciferase and diphtheria
      toxin a genes in HeLa cells infected with or expressing HIV.
AB  - HIV-regulated expression of the diphtheria toxin A fragment gene (HIV-DT-A) is a
      potential gene therapy approach to AIDS. Since cationic liposomes are safe and
      non-immunogenic for in vivo gene delivery, we examined whether LipofectAMINE or
      DMRIE reagent could mediate the transfection of HIV-DT-A (pTHA43) or the HIV
      regulated luciferase gene (pLUCA43) into HIV-infected or uninfected HeLa cells.
      pLUCA43 was expressed at a 10(3)-fold higher level in HeLa/LAV cells than in
      uninfected HeLa cells, while the extent of expression of RSV-regulated luciferase
      was the same in both cell lines. Co-transfection of HeLa cells with pTHA43 and
      the proviral HIV clone, HXB deltaBgl, resulted in complete inhibition of virus
      production. In contrast, the delivery of HIV-DT-A to chronically infected
      HeLa/LAV or HeLa/IIIB cells, or to HeLa CD4+ cells before infection, did not have
      a specific effect on virus production, since treatment of cells with control
      plasmids also reduced virus production. This reduction could be ascribed to
      cytotoxicity of the reagents. The efficiency of transfection, as measured by the
      percentage of cells expressing beta-gal, was approximately 5%. Thus, cationic
      liposome-mediated transfection was too inefficient to inhibit virus production
      when the DT-A was delivered by cationic liposomes to chronically- or de novo-
      infected cells. However, when both the virus and DT-A genes were delivered into
      the same cells by cationic liposomes, DT-A was very effective at inhibiting virus
      production. Our results indicate that the successful use of cationic liposomes
      for gene therapy will require the improvement of their transfection efficiency.

PMID- 9150277
TI  - Effect of caffeine on mucus secretion and agonist-dependent Ca2+ mobilization in
      human gastric mucus secreting cells.
AB  - Caffeine is known to stimulate gastric acid secretion, but, the effects of
      caffeine on gastric mucus secretion have not been clarified. To elucidate the
      action of caffeine on gastric mucin-producing cells and its underlying mechanism,
      the effects of caffeine on mucus glycoprotein secretion and agonist-induced
      [Ca2+]i mobilization were examined in human gastric mucin secreting cells (JR-I
      cells). The measurement of [Ca2+]i using Indo-1 and the whole cell voltage clamp
      technique were applied. Mucus glycoprotein secretion was assessed by release of
      [3H]glucosamine. Caffeine by itself failed to increase [Ca2+]i and affect
      membrane currents, while it dose-dependently inhibited agonist (acetylcholine
      (ACh) or histamine)-induced [Ca2+]i rise, resulting in inhibiting activation of
      Ca2+-dependent K+ current (I(K.Ca)) evoked by agonists. The effect of caffeine
      was reversible, and the half maximal inhibitory concentration was about 0.5 mM.
      But, caffeine did not suppress [Ca2+]i rise and activation of I(K.Ca) induced by
      A23187 or inositol trisphosphate (IP3). Theophylline or 3-isobutyl-1-methyl
      xanthine (IBMX) did not mimic the effect of caffeine. Caffeine failed to
      stimulate mucus secretion, while it significantly decreased ACh-induced mucus
      secretion. These results indicate that caffeine selectively inhibits agonist
      mediated [Ca2+]i rise in human gastric epithelial cells, probably through the
      blockade of receptor-IP3 signaling pathway, which may affect the mucin secretion.

PMID- 9150278
TI  - A characterization of permolybdate and its effect on cellular tyrosine
      phosphorylation, gap junctional intercellular communication and phosphorylation
      status of the gap junction protein, connexin43.
AB  - Biological and analytical characterizations of permolybdate (a mixture of H2O2
      and molybdate) were done. Molybdate (10 mM) and molybdenum(V) chloride (3 mM) did
      not affect gap junctional intercellular communication (GJIC), phosphorylation
      status of connexin43 (Cx43) or cellular tyrosine phosphorylation in early passage
      hamster embryonic cells (mainly fibroblast-like). High concentrations of H2O2 (3
      10 mM) affected some of the parameters. Acidified permolybdate was clearly more
      stable than the unadjusted permolybdate. The maximum biological potency of
      acidified permolybdate was found at a molar ratio of 2:1 (H2O2:molybdate). The
      mixtures of molybdenum(V) chloride and H2O2 gave a maximum effect at 4:1 molar
      ratio (H2O2:molybdenum(V)). This can be explained by decomposition of H2O2 and by
      the generation of less biologically active compounds. Spectrophotometric analyses
      of the mixtures corroborated the biological results. The Mo(V) electron spin
      resonance spectrum disappeared upon addition of H2O2 to Mo(V) solutions, and no
      spectrum appeared when H2O2 was mixed with Mo(VI). Thus, permolybdate is probably
      diperoxomolybdate, a Mo(VI) compound. Regardless of the parent metal salt, the
      H2O2/metal salt mixtures showed concentration-dependent biphasic responses with
      an initial decrease in GJIC followed by an increase. A dissociation between
      alteration in Cx43 phosphorylation status and GJIC was obtained under certain
      conditions. The biological activities of permolybdate were only partially
      mimicked by phenylarsine oxide, an alternative protein tyrosine phosphatase
      inhibitor.

PMID- 9150279
TI  - Stimulation of atrial natriuretic peptide receptor/guanylyl cyclase- A signaling
      pathway antagonizes the activation of protein kinase C-alpha in murine Leydig
      cells.
AB  - Atrial natriuretic peptide (ANP) regulates diverse physiological responses by
      binding to its specific guanylyl cyclase-A receptor (Npra) which synthesizes the
      intracellular second messenger cGMP. To understand the molecular mechanisms of
      cellular signaling of ANP, we have studied its effect on the enzymatic activity
      of overexpressed protein kinase C (PKC) in murine Leydig tumor (MA-10) cells
      which were transfected with PKC-alpha cDNA. Treatments with 12-O
      tetradecanoylphorbol-13-acetate (TPA), angiotensin II (ANG II) and endothelin-1
      (ET-1) stimulated the PKC activity by 4-5-fold in PKC-alpha cDNA transfected MA
      10 cells. The pretreatment of PKC-alpha transfected cells with ANP significantly
      inhibited the TPA-, ANG II- and ET-1-stimulated PKC activity. The agonist
      stimulated PKC activity was also inhibited in the presence of 8-bromo-cGMP,
      however, cAMP had no effect on stimulatory PKC activity. The exposure of cells to
      Npra- antagonist A71915, which blocks the production of cGMP, significantly
      reduced the inhibitory effect of ANP on agonist-stimulated PKC activity and
      accumulation of intracellular cGMP in MA-10 cells. Similarly, inhibition of cGMP
      dependent protein kinase by KT5823, restored the stimulatory levels of PKC
      activity in the presence of ANP. These results provide direct evidence that ANP
      antagonizes the agonist-stimulated PKC activity in MA-10 cells, involving the
      specific receptor Npra, its second messenger cGMP and cGMP-dependent protein
      kinase. Together, these findings implicate that ANP may act as a negative
      mediator of 'cross-talk' between PKC-alpha and Npra signaling pathway in MA-10
      cells.

PMID- 9150280
TI  - Expression and signal transduction of the glucagon receptor in betaTC3 cells.
AB  - The expression and signal transduction of the glucagon receptor (GR) have been
      studied in betaTC3 cells. Northern blot and RT-PCR analysis indicated the
      expression of the GR gene in betaTC3 cells. One-5 nM glucagon stimulated a 2.5
      fold increase in the IP(S) production. At glucagon concentrations higher than 5
      nM, the production of IP(S) was blunted but not abolished. The accumulation of
      intracellular cAMP was observed following the stimulation with 5 nM of glucagon.
      A maximal 4.5-fold increase in cAMP was observed using 250 nM glucagon and
      higher. Comparative studies using a glucagon anatogonist, des-His1[Glu]9glucagon,
      showed no effect on intracellular cAMP and IPs in betaTC3 cells. Our data shows
      that the GR gene is expressed in betaTC3 cells. The GR in betaTC3 cells transmits
      its intracellular signal by causing the accumulation of both IP(S) and cAMP.

PMID- 9150281
TI  - T cell antigen receptor dependent signalling in human lymphocytes: cholera toxin
      inhibits interleukin-2 receptor expression but not interleukin-2 synthesis by
      preventing activation of a protein kinase C isotype, PKC-alpha.
AB  - Activation and translocation of protein kinases C is a key event in the
      regulation of T lymphocyte activation, proliferation and function. Stimulation of
      human peripheral blood lymphocytes with the monoclonal antibody BMA 031 raised
      against the T cell antigen receptor led to a bimodal activation of protein
      kinases C. The immediate activation and translocation of the protein kinase C
      isoform PKC-alpha was followed by activation and translocation of the protein
      kinase C-beta isoenzyme after 90 min of stimulation. Pretreatment of the cells
      with cholera toxin for 90 min completely abolished activation of protein kinase C
      alpha. In sharp contrast, activation and translocation of protein kinase C-beta
      was not influenced by the bacterial toxin, suggesting that activation and
      translocation of different protein kinase C isoenzymes are regulated by distinct
      mechanisms of transmembrane signalling coupled to the T cell antigen receptor/CD3
      complex. The expression of high affinity IL-2 receptors was completely inhibited
      by cholera toxin, while IL-2 synthesis and secretion were not influenced in BMA
      031-stimulated human lymphocytes. Extensive control experiments have shown that
      the effects of cholera toxin were not mediated by its B subunit, and were
      independent of elevation of intracellular cAMP concentration, suggesting that
      cholera toxin interfered with a signalling pathway leading to activation of
      protein kinase C-alpha, which could be responsible for the inhibition of IL-2
      receptor expression. This hypothesis was substantiated by the finding that upon
      introduction of antibodies against protein kinase C-alpha, IL-2 receptor gene
      expression was completely suppressed. The results suggest, that protein kinase C
      alpha might be the major protein kinase C isoenzyme of a signal transduction
      cascade regulating IL-2 receptor expression in stimulated human lymphocytes.

PMID- 9150282
TI  - On the dorsal columns: translating basic research hypotheses to the clinic.

PMID- 9150283
TI  - An update on the clinical use of methadone for cancer pain.
AB  - Methadone is a synthetic opioid agonist considered a second choice drug in the
      management of cancer pain. Methadone has a number of unique characteristics
      including excellent oral and rectal absorption, no known active metabolites, high
      potency, low cost, and longer administration intervals, as well as an incomplete
      cross-tolerance with respect to other mu-opioid receptor agonist drugs. For these
      reasons, methadone has the potential of playing a major role in the treatment of
      cancer pain. However, its use is limited by the remarkably long and unpredictable
      half-life, large inter-individual variations in pharmacokinetics, the potential
      for delayed toxicity, and above all by the limited knowledge of correct
      administration intervals and the equianalgesic ratio with other opioids when
      administered chronically. Recent findings suggest that standard equianalgesic
      tables are unreliable for methadone titration in patients tolerant to high doses
      of opioid agonists and that switchovers should take place slowly and should be
      personalized. Future research has to better define the variation in both
      bioavailability and elimination of methadone in different patient populations,
      the interaction between methadone and the most commonly used drugs in cancer
      patients, the type and activity of potential methadone metabolites, and the
      equianalgesic doses between methadone and the most commonly used opioids.

PMID- 9150284
TI  - Pain syndromes and etiologies in ambulatory AIDS patients.
AB  - Ambulatory AIDS patients participating in a quality of life study were recruited
      for an assessment of pain syndromes. Of 274 patients with pain, 151 (55%)
      consented to the assessment which included a clinical interview, neurologic
      examination, and review of medical records. The number, type, and etiology of
      pains were evaluated in terms of risk factors, age, sex, CD4+ lymphocyte count,
      and performance status. The average number of pains per patient was 2.7 (range, 1
      7), yielding a total of 405 pains. The most common pain diagnoses were headache
      (46% of patients; 17% of all pains), joint pain (31% of patients; 12% of pains),
      pain due to polyneuropathy (28% of patients; 10% of pains), and muscle pain (27%
      of patients; 12% of pains). Pathophysiology was inferred for all pain syndromes
      (except for headache), 45% of pain syndromes were somatic in nature, 15% were
      visceral, 19% were neuropathic, and 4% were unknown, psychogenic, or idiopathic;
      17% of pains were classified as headache, hence pathophysiology could not be
      determined. Pain resulted from diverse etiologies, including the direct effects
      of HIV/AIDS-related conditions (30%) pre-existing unrelated conditions (24%), and
      therapies for HIV/AIDS and related conditions (4%). The latter category, pain
      related to HIV therapies, occurred in 11% of patients. In 37% of the pains, the
      etiology could not be determined from the information available. In univariate
      analyses, lower CD4+ cell counts were significantly associated with
      polyneuropathy (P < 0.05) and headache (P < 0.05), and female gender was
      significantly associated with the presence of headache (P < 0.05) and
      radiculopathy (P < 0.001). These data confirm the diversity of pain syndromes in
      AIDS patients, clarify the prevalence of common pain types, and suggest
      associations between specific patient characteristics and pain syndromes. The
      large proportion of patients who could not be given a diagnosis underscores the
      need for a careful diagnostic evaluation of pain in this population.

PMID- 9150285
TI  - Effect of transient naloxone antagonism on tolerance development in rats
      receiving continuous spinal morphine infusion.
AB  - The magnitude of tolerance and dependence is defined in part by agonist
      concentration and duration of receptor exposure. Therefore, in the face of
      continued exposure to an opioid agonist, periodic reduction in opiate receptor
      occupancy should reduce tolerance. Alternately, we have shown that reversal of
      opiate agonist action yields increased glutamate release and NMDA-antagonist
      studies indicated that this release may lead to an exacerbation of tolerance. To
      address this issue, we observed the effect of transient daily antagonism by
      naloxone of otherwise continuous opioid receptor exposure on morphine tolerance
      development. Rats with intrathecal (i.t.) catheters and osmotic minipumps were
      assigned to one of the following 7-day infusion/treatment groups: group A: i.t.
      morphine (20 nmol/h) with daily subcutaneous (s.c.) injection of naloxone 0.6
      mg/kg, group B: i.t. morphine (20 nmol/h) with daily s.c. saline, group C: i.t.
      saline (1 microl/h) with daily s.c. injection of naloxone 0.6 mg/kg, or, group D:
      i.t. saline (1 microl/h) with daily s.c. saline. Hot plate response latency was
      measured daily before and after the s.c. injection. The infusion was discontinued
      on day 7 and on day 8 the response of the rat to a probe dose of i.t. morphine
      (60 nmol) given as a bolus was observed. Elevated hot plate latencies were
      observed for groups A and B on day 1 of infusion and this declined over the
      following 3-4-day interval. Group B approached baseline, but by day 5 group A
      showed a mild hyperalgesia prior to each naloxone injection. Groups C and D
      showed no change in baseline latency. On day 8, 24 h after termination of
      morphine infusion, the magnitude of the analgesic response to the probe i.t.
      morphine was: group D = group C > group B > group A (P < 0.05, 1-way ANOVA).
      Thus, in contrast to the expectation that tolerance would be reduced by periodic
      blockade of opiate receptor occupancy, rats that had daily transient receptor
      antagonism showed a greater tolerance than rats with simple continuous receptor
      occupancy. These results are, however, consistent with work showing that (i)
      naloxone will evoke spinal glutamate release in spinal morphine tolerant rats and
      (ii) spinal NMDA receptor antagonism ameliorates loss of opiate effect in this
      spinal infusion model.

PMID- 9150286
TI  - Relationship between mechano-receptive fields of dorsal horn convergent neurons
      and the response to noxious immersion of the ipsilateral hindpaw in rats.
AB  - This study examines the relationship between mechano-receptive fields (inhibitory
      and excitatory, located on the ipsilateral hindpaw) of convergent dorsal horn
      neurons, and the responses of the neurons to noxious immersion of an entire paw
      in noxious hot water. In pentobarbital anesthetized rats with intact spinal cords
      and in unanesthetized decerebrate-spinalized rats, rat hindpaws were immersed in
      50 degrees C water for 10 s after the mechano-receptive fields had been
      delineated using 5-s noxious pinches. Convergent neurons were either excited or
      inhibited by noxious immersion of the hindpaw. In both groups, a significant
      association (chi2, P < 0.01) was found between the make-up of the mechano
      receptive field and the response of the neuron to immersion. Immersion-inhibited
      neurons (intact = 27, spinalized = 13), always had both an excitatory and an
      inhibitory mechano-receptive field on the same hindpaw. Additionally, when the
      hindpaw was removed from the noxious water, these immersion-inhibited cells
      displayed a strong afterdischarge which was immediately inhibited once the paw
      was reimmersed. Pinch-induced and immersion-induced inhibition were found in both
      spinalized and intact rats suggesting spinal mechanisms were sufficient to
      mediate this effect. The majority of immersion-excited cells showed only an
      excitatory mechano-receptive field on the hindpaw (intact rats = 18/23 or 78.3%,
      spinalized rats = 24/36 or 66.7%). However, other immersion-excited cells had
      both an inhibitory and an excitatory mechano-receptive field on the hindpaw
      (intact rats = 5/23 or 21.7%, spinalized rats = 12/36 or 33.3%). The response of
      a convergent neuron, which has its excitatory receptive field located on a paw,
      to noxious immersion of the entire paw can be predicted by the make-up of the
      mechano-receptive fields. Additionally, since noxious paw immersion affects
      ipsilateral convergent neurons in two opposite manners, it suggests that other
      effects, such as heterotopic actions, might also not be uniform.

PMID- 9150288
TI  - Habituation and the interference of pain with task performance.
AB  - Pain interrupts, distracts and is difficult to disengage from. In this experiment
      the attentional interference during pain is studied with a primary task paradigm.
      We were interested in the strength of attentional interference with repeated
      presentations of pain. Healthy volunteers (n = 24) performed a tone
      discrimination task in the presence of two types of distractors (an electrical
      pain stimulus and a control stimulus) which they were instructed to ignore. On
      some trials, tone probes were presented immediately (250 ms) after distractor
      onset, further on (750 ms) during the distractor, and immediately (250 ms) after
      distractor offset. Habituation of the task interference during the early
      processing of both the pain and the control stimulus was observed. It was also
      found that the attentional interference during pain did not completely disappear
      with repeated presentations. Finally, results clearly showed a more prolonged
      processing time of the tones during pain trials than during control trials. These
      results are discussed in terms of cognitive theories of habituation.

PMID- 9150287
TI  - Antinociceptive effects of dynorphin peptides in a model of inflammatory pain.
AB  - Dynorphin A (DYN) peptides, administered into the central nervous system, have
      produced inconsistent analgesic actions in tests using thermal stimuli. This
      study examined antinociceptive effects of intravenous and intraplantar DYN-(2-17)
      against noxious pressure in rats with Freund's adjuvant-induced unilateral
      hindpaw inflammation. The effects of DYN-(2-17) were compared to those of the
      opioid agonists morphine. (D-Ala2,N-Methyl-Phe4,Gly-ol5)-enkephalin (DAMGO) and
      DYN-(1-17). Intravenous DYN-(2-17) (0.188-10 mg/kg) produced dose-dependent
      elevations of paw pressure thresholds in inflamed and in non-inflamed paws. These
      effects were similar in magnitude to those of subcutaneous morphine (2 mg/kg), at
      doses of 0.375-1.5 mg/kg they were significantly greater on the inflamed (right)
      than on the non-inflamed (left) paw, and they were not reversible by intravenous
      naloxone (1-10 mg/kg). Intraplantar Dyn-(2-17)(0.001-0.3 mg) was ineffective,
      whereas both intraplantar DYN-(1-17)(0.15-0.3 mg) and DAMGO (0.008-0.016 mg)
      produced dose-dependent and naloxone-reversible elevations of paw pressure
      thresholds. The intraplantar injection of both Dyn peptides produced a transient
      increase in the volume of non-inflamed paws. These findings suggest that
      intravenous DYN-(2-17) produces possibly centrally mediated, non-opioid
      antinociceptive effects against noxious pressure. At certain doses these effects
      are more potent in inflamed than in non-inflamed paws. In contrast to the opioid
      peptides DYN-(1-17) and DAMGO, DYN-(2-17) does not appear to have no peripheral
      antinociceptive actions.

PMID- 9150289
TI  - Neomycin and gadolinium applied to an L5 spinal nerve lesion prevent mechanical
      allodynia-like behaviour in rats.
AB  - In male Wistar rats, the left ventral ramus of the L5 spinal nerve (RvL5) was
      cut, and animals were tested for allodynia-like behaviour in response to
      mechanical stimuli which were applied with von Frey hairs (4.3-205 mN) to the
      plantar skin of the hindpaw supplied by the intact L4 spinal nerve. After
      surgery, allodynia-like behaviour was evoked prominently on the operated (left)
      side and weakly on the contralateral (right) side. Eleven sham-operated rats
      displayed low levels of allodynia-like behaviour on the operated side comparable
      to that seen contralateral to the lesion in nerve-transected animals. In 14 rats,
      allodynic behaviour to mechanical stimuli on either side was dose dependently and
      permanently reduced, after 4-32 mg of the antibiotic Nebacetin had been applied
      locally at the transection site immediately after cutting the nerve. The same
      effect was observed when one of the active compounds of Nebacetin, neomycin, but
      not the other, bacitracin, was applied by continuous local infusion. Allodynia
      like behaviour to stimuli between 4.3 mN and 124 mN was also prevented when 1-8
      mg gadolinium acetate was applied at the transection site, whereas allodynic
      behaviour to stimuli of 205 mN was not affected at least for the first 7 days
      after the lesion. Both gadolinium and Nebacetin failed to prevent allodynic
      behaviour when applied later than 7 h after the nerve lesion. Neither substance
      interfered with the development of tactile allodynia when applied to the nerve
      rostral to the lesion site. The results suggest that Nebacetin and gadolinium
      interfere with the mechanisms at the RvL5 transection site crucial for the
      initiation of sensitisation of dorsal horn neurones and the development of
      mechanical allodynia.

PMID- 9150290
TI  - Experimental evaluation of the analgesic effect of ibuprofen on primary and
      secondary hyperalgesia.
AB  - The analgesic effect of systemic ibuprofen was investigated with two human
      experimental pain models: (i) static mechanical stimulation of the inter digital
      web between the 2nd and 3rd finger and (ii) primary and secondary hyperalgesia
      induced by a 7-min burn injury on the calf. In each double-blind, randomized, two
      way cross-over study 20 healthy male volunteers received either ibuprofen 600 mg
      or placebo tablets. Ibuprofen reduced pain evoked by static mechanical pressure
      in normal skin and by motor brush stimulation in the area of secondary
      hyperalgesia following burn injury. In contrast, ibuprofen did not reduce the
      area of secondary hyperalgesia to either pinprick or stroke following burn
      injury. Previous human experimental studies concerning the analgesic effect of
      NSAIDs are reviewed. Based on the previous literature and the present results we
      suggest that NSAIDs inhibit progressive tactile hypersensitivity but not the
      central sensitization itself.

PMID- 9150291
TI  - Developments in the treatment of cancer pain in Finland: the third nation-wide
      survey.
AB  - This survey was designed to investigate the current status of the management of
      cancer pain in Finland. In 1995 a questionnaire was randomly sent to 5% (n = 546)
      of Finnish physicians, excluding specialists not expected to treat cancer
      patients. Two previous surveys, using the same questionnaire, were conducted in
      1985 and 1990 by Vainio. The response rate was 53%. Seventy-nine percent of the
      respondents treated one or less than one cancer patient a week. Sixty-seven
      percent of them assessed the severity of cancer pain in their patients as being
      at least moderate. In 10 years, the proportion of physicians suggesting the WHO
      analgesic ladder principle to their 'typical cancer patient' had increased from
      12% to 28%. At the same time, the suggestions of 'analgesic' without definition
      had decreased from 48% to 6%. Three simulated patient cases were presented. The
      mean daily dose of opioids suggested for severe terminal cancer pain corresponded
      to 72 (18-300) mg of intramuscular morphine in 1995, being only 39 (1-77) mg in
      1985 for the same simulated patient case. Continuous infusion of opioid was
      recommended by 59% of the respondents. Non-steroidal anti-inflammatory drugs as
      the treatment of choice for bone metastases pain in a patient with breast cancer,
      was recommended by 68% of the respondents. In the case of local severe pain due
      to recurrent rectal cancer, 63% of the physicians suggested anaesthetic
      intervention. Insufficient pain relief and lack of experience were the most
      common difficulties in pain management. Only one-third of the physicians thought
      that they had enough time and ability to give sufficient psychological support to
      their patients.

PMID- 9150292
TI  - Tonic pain: a SPET study in normal subjects and cluster headache patients.
AB  - Whether the pathogenesis of cluster headache (CH) is peripheral or central is
      still matter of debate. An involvement of central structures related to pain
      perception and modulation, which also causes an alteration of the physiological
      pattern of pain perception in CH, has been hypothesized. We investigated the
      pattern of brain response to pain in normal subjects and CH patients by
      evaluating the cerebral blood flow (CBF) changes using an experimental model of
      tonic aching pain stimulation, the cold water pressor test (CWPT). CBF was
      assessed quantitatively by the Xe-133 inhalation method and single photon
      emission tomography (SPET), at rest and during CWPT, as previously described (Di
      Piero et al., 1994). CWPT was performed in 12 volunteers and in seven patients
      with CH. All the CH patients had a left-sided headache and were studied in a
      headache-free phase out of the cluster period. During CWPT, volunteers showed a
      significant CBF increase in the contralateral primary sensorimotor (P < 0.001),
      frontal (P < 0.01) and temporal (P < 0.002) regions and thalamus (P < 0.01) and
      in the ipsilateral temporal (P < 0.005) and anterior cingulate (P < 0.01)
      regions. During left-hand stimulation (ipsilateral to the headache side) by CWPT
      in CH patients, CBF changes were significantly lower than those observed in
      volunteers in the contralateral primary sensorimotor region (P < 0.0005) and
      thalamus region (P < 0.01). There were no significant differences in the brain
      response observed during the stimulation of the hand contralateral to the
      headache side. In conclusion, in a headache-free phase out of the cluster period,
      the pattern of cerebral activation during tonic pain stimulation of the hand
      ipsilateral to the headache side is critically modified in CH patients in areas
      which are probably involved in the detection of the stimulus intensity. This
      modification may reflect a marker of a biological modification of the pain
      conveyance system. The fact that it is also present out of the active period of
      the disease, suggests a possible involvement of central tonic pain mechanisms in
      the pathogenesis of CH.

PMID- 9150293
TI  - Paracetamol with and without codeine in acute pain: a quantitative systematic
      review.
AB  - In order to assess the analgesia obtained from single oral doses of paracetamol
      alone and in combination with codeine in postoperative pain, we conducted a
      systematic review of randomised controlled trials. We found 31 trials of
      paracetamol against placebo with 2515 patients, 19 trials of paracetamol plus
      codeine against placebo with 1204 patients and 13 trials of paracetamol plus
      codeine against the same dose of paracetamol with 874 patients. Pain relief
      information was extracted, and converted into dichotomous information (number of
      patients with at least 50% pain relief). Wide variations in responses to placebo
      (0-72%) and active drug (3-89%) were observed. In postoperative pain states
      paracetamol 1000 mg alone against placebo had an number-needed-to-treat (NNT) of
      3.6 (3.0-4.4) and paracetamol 600/650 mg alone an NNT of 5.0 (4.1-6.9).
      Paracetamol 600/650 mg plus codeine 60 mg against placebo had a better NNT of 3.1
      (2.6-3.8), with no overlap of 95% confidence intervals with paracetamol 600/650
      mg alone. In direct comparisons of paracetamol plus codeine with paracetamol
      alone the additional analgesic effect of 60 mg of codeine added to paracetamol
      was 12 extra patients in every 100 achieving at least 50% pain relief. In
      indirect comparisons of each with placebo it was 14 extra patients per 100. This
      was an NNT for adding codeine 60 mg of 9.1 (5.8-24). The results confirm that
      paracetamol is an effective analgesic, and that codeine 60 mg added to
      paracetamol produces worthwhile additional pain relief even in single oral doses.

PMID- 9150294
TI  - Diminishing returns or appropriate treatment strategy?--an analysis of short-term
      outcomes after pain clinic treatment.
AB  - In the United Kingdom patients with chronic pain are frequently managed in
      anaesthetist-led outpatient pain clinics. In many of these clinics the emphasis
      is on medical therapies (analgesics and psychotropic drugs, TENS, acupuncture and
      nerve blocks) with patients trying a series of different therapies until relief
      is achieved or further attempts at physical treatments are discontinued. The
      sequential trial of different treatment modalities presents clinicians with a
      problem. Patients who receive little benefit from (say) the first three
      treatments tried might be expected to be less likely to gain benefit from the
      next treatment modality. The presence or absence of such 'diminishing returns'
      from treatment will influence when therapeutic efforts based on the medical model
      of pain should be abandoned. This study examined basic outcome data on 1912
      patients seen in a single Scottish pain clinic between 1987 and 1994. The data
      were analysed to assess whether the success of treatment modalities depended on
      whether they were used as a first-choice treatment or were given after previous
      therapeutic attempts had failed. Diminution in success rates was generally not
      large although this varied between therapies. No fall-off in success rates was
      seen for antidepressants, acupuncture or sympathetic nerve blocks. However, the
      other nerve blocks all showed falling success rates when they were used as fourth
      or fifth-line treatments. That little diminution of success rates was seen
      warrants further investigation. Pain clinics need good information on the success
      or otherwise of late treatment so that they can devise rational pain management
      strategies covering multiple therapies and appropriate criteria for ending
      medical interventions. These findings suggest that allowing patients access to
      multiple pain therapies may well be an appropriate management strategy.

PMID- 9150296
TI  - Systemic physostigmine increases the antinociceptive effect of spinal morphine.
AB  - In this study we evaluated the antinociceptive effect of concurrent intrathecal
      (i.t.) and subcutaneous (s.c.) administration of morphine and physostigmine,
      respectively. The experiments were performed on male Wistar rats. Intrathecal
      administration of morphine was performed through a catheter implanted in the
      subarachnoid space. The 'tail-immersion' test was used to measure animals'
      responses to evoked nociceptive stimuli. Interaction of drugs was analyzed using
      a dose addition model. Both i.t. (1-5 microg) administration of morphine and s.c.
      (50-250 microg/kg) administration of physostigmine increased the latencies of
      nociceptive responses in a dose-dependent manner. Two micrograms of i.t. morphine
      and 100 microg/kg of s.c. physostigmine demonstrated 31.6 +/- 10.6 and 34.2 +/-
      11.4 percentage of maximal possible effect (%MPE), respectively. Simultaneous
      administration of 1 microg of i.t. morphine and 50 microg/kg of s.c.
      physostigmine produced a %MPE equal to 84.8 +/- 16.9. Thus, combined
      administration of 1 microg i.t. morphine and 50 microg/kg s.c. physostigmine
      resulted in a strong, highly significant antinociceptive effect. This effect was
      much higher than the effect expected if both drugs acted in an additive manner.
      Supra-additive interaction observed in this study might be a result of
      simultaneous activation of different neurotransmitter systems involved in
      nociceptive processing at the spinal as well as at the supraspinal level of the
      CNS.

PMID- 9150295
TI  - Blockade of peripheral neuronal barrage reduces postoperative pain.
AB  - Peripheral afferent neuronal barrage from tissue injury produces central nervous
      system hyperexcitability which may contribute to increased postoperative pain.
      Blockade of afferent neuronal barrage has been reported to reduce pain following
      some, but not all, types of surgery. This study evaluated whether blockade of
      sensory input with a long-acting local anesthetic reduces postoperative pain
      after the anesthetic effects have dissipated. Forty-eight patients underwent oral
      surgery with general anesthesia in a parallel group, double-blind, placebo
      controlled study. Subjects randomly received either 0.5% bupivacaine or saline
      intraoral injections, general anesthesia was induced with propofol, a non-opioid
      anesthetic, and 2-4 third molars extracted. Subjects were assessed at 24 and 48 h
      for postoperative pain and analgesic intake. Blood samples were collected at
      baseline, intraoperatively and at 1-h intervals postoperatively for measurement
      of beta-endorphin as an index of CNS response to nociceptor input. Plasma beta
      endorphin levels increased significantly from baseline to the end of surgery in
      the saline group in comparison to the bupivacaine group (P < 0.05), indicating
      effective blockade of nociceptor input into the CNS by the local anesthetic. Pain
      intensity was not significantly different between groups at 24 h. Pain at 48 h
      was decreased in the bupivacaine group as measured by category scale and graphic
      rating scales for pain and unpleasantness (P < 0.05). Additionally, subjects in
      the bupivacaine group self-administered fewer codeine tablets for unrelieved pain
      over 24-48 h postoperatively (P < 0.05). These data support previous animal
      studies demonstrating that blockade of peripheral nociceptive barrage during and
      immediately after tissue injury results in decreased pain at later time points.
      The results suggest that blockade of nociceptive input by administration of a
      long-acting local anesthetic decreases the development of central
      hyperexcitability, resulting in less pain and analgesic intake.

PMID- 9150297
TI  - Intrathecal pertussis toxin produces hyperalgesia and allodynia in mice.
AB  - Pertussis toxin (PTX), which causes the ADP-ribosylation and thereby inactivation
      of Gi-proteins, has been employed in analgesia testing to elucidate receptors
      that are coupled to inhibitory G-proteins, such as the mu-opioid receptor.
      Consistent with previous findings, the antinociceptive effects of morphine (1-10
      microg) as measured by tail-flick latency using a 55 degrees C water bath, were
      blocked by a single intrathecal injection of 0.5 microg PTX 6 days prior to
      intrathecal morphine administration. In addition, mice treated intrathecally with
      0.5 microg of PTX had significantly shorter baseline tail-flick latencies
      compared with vehicle treated mice using a 55 degrees C water bath when tested 6
      days after PTX or vehicle administration. Morphine-induced antinociception was
      blocked in a dose-dependent manner by PTX with complete blockade of morphine
      following a 0.3-microg dose of PTX. Further, mice administered 0.1 microg or 0.3
      microg PTX intrathecally had significantly shorter tail-flick latencies compared
      with vehicle injected mice using a 40, 45 or 50 degrees C water bath when tested
      7 days after intrathecal injection. Shorter tail-flick latencies were observed at
      45 degrees C as early as 48 h after intrathecal administration of 0.03, 0.1 or
      0.3 microg PTX and these shorter tail-flick latencies were observed up to 90 days
      after intrathecal PTX administration. The intrathecal administration of PTX
      caused hyperalgesia and allodynia that appears similar to the symptoms reported
      by patients suffering from neuropathic pain, and suggests that deficiencies in
      inhibitory systems, as compared with increases in excitatory systems, may play a
      role in the pathophysiology of at least some central or neuropathic pain states.

PMID- 9150298
TI  - Development of a brief version of the Survey of Pain Attitudes.
AB  - Because patient attitudes and beliefs about pain have been shown to affect
      treatment outcomes and adjustment to illness, a number of self-report instruments
      have been developed assess those constructs. The Survey of Pain Attitudes (SOPA)
      is a well-researched instrument that assesses patient feelings about pain
      control, solicitude (solicitous responses from others in response to one's pain),
      medication (as appropriate treatment for pain), pain-related disability, pain and
      emotions (the interaction between emotions and pain), medical cures for pain, and
      pain-related harm (pain as an indicator of physical damage or harm). The factor
      structure of the SOPA, however, has not been verified and its length makes its
      administration cumbersome. The present study examined the factor structure of the
      SOPA and developed a brief 30-item version of the original. Factor analysis
      showed that the SOPA did not contain seven unique dimensions. The brief version
      (the SOPA-B), however, clearly reflected the seven dimensions described for the
      SOPA. The psychometric properties of the SOPA-B were comparable to those of the
      SOPA. The SOPA-B appears to be a practical, easily-administered alternative to
      the longer version.

PMID- 9150300
TI  - Sodium urate arthritis: effects on the sensory properties of articular afferents
      in the chicken.
AB  - The physiological properties of joint capsule mechanoreceptors in the ankle joint
      of the chicken were studied in the 3-h period immediately after intra-articular
      injection of microcrystal sodium urate. The electrical activity was recorded from
      single C- and A-delta sensory fibres dissected from the parafibular nerve. C
      fibres showed high levels of spontaneous activity and receptive fields that
      varied from single spots 1 mm in diameter up to 4 x 4 mm. Thresholds to
      mechanical stimulation ranged from 0.1 to 8 g and 80% of the units responded to
      movement of the joint. A-delta fibres showed little spontaneous activity and
      receptive fields that varied from 1 mm to 9 x 1 mm. Thresholds to mechanical
      stimulation ranged from 0.1 to 16 g and 17% responded to joint movement. A
      comparison of the physiological properties of the C- and A-delta fibres in sodium
      urate arthritis with similar fibres in normal and monoarthritic animals indicated
      an increased sensitivity in the C-fibres but not in the A-delta fibres.
      Sensitisation was observed in the significantly increased receptive field size,
      decreased response thresholds, increased response to joint movement and the high
      level of spontaneous activity. These changes in the sensitivity of the joint
      capsule C-fibre receptors provides peripheral neural evidence for the pain
      experienced in acute gouty arthritis.

PMID- 9150301
TI  - Changes in formalin-evoked spinal Fos expression and nociceptive behaviour after
      oral administration of Bufferin A (aspirin) and L-5409709 (ibuprofen + caffeine +
      paracetamol).
AB  - This study compares the effects of two non-steroidal anti-inflammatory drugs,
      Bufferin A (BA) and L-5409709 (L-54), on nociceptive behaviour and spinal Fos
      expression induced by subcutaneous formalin in the rat. BA contains aspirin. L-54
      contains ibuprofen, caffeine and paracetamol. Doses based on the human posology
      were administered orally 30 or 40 min before subcutaneous intraplantar injection
      of formalin (1.5%, 50 microl) in the right hindpaw. Low doses (BA, 24 mg/kg; L
      54, 21.5 mg/kg) did not significantly affect the behavioural pain response. High
      doses (BA, 480 mg/kg; L-54, 430 mg/kg) reduced the late phase of the response by
      42% and 62% respectively, but did not affect the early phase of the response. No
      sedative side-effects were observed. The two drugs had different effects on the
      number of spinal Fos-like immunoreactive neurones 2 h after the formalin
      injection. Fos expression was reduced after BA treatment, and this reduction was
      correlated to and matched the reduction of the pain response. In contrast, Fos
      expression after L-54 treatment was not reduced and was not correlated to the
      reduction in the pain response. The Fos results reveal clear differences in the
      way that BA (aspirin) and L-54 (ibuprofen + caffeine + paracetamol) affected
      transmission of the noxious signal. They suggest that BA did not act beyond the
      spinal cord and that L-54 had more central sites of action than BA.

PMID- 9150299
TI  - Rapid sprouting of sympathetic axons in dorsal root ganglia of rats with a
      chronic constriction injury.
AB  - We compared the time-course of sympathetic nerve sprouting into the L4-6 dorsal
      root ganglia (DRG) of adult rats following a chronic constriction injury (CCI)
      made on the sciatic nerve, or following sciatic nerve transection at the same
      site. We also tested the rats for changes in threshold for withdrawal from
      mechanical and thermal stimuli delivered to the hindpaws. We found sympathetic
      sprouting in DRG by 4 days following CCI, paralleling the decreases in
      mechanosensory threshold and preceding changes in thermal thresholds. However,
      with sciatic nerve transection, sympathetic sprouting was not detectable until 14
      days after nerve injury. Thus, after CCI, sympathetic sprouting occurs with a
      sufficiently rapid time-course for it to play a role in the genesis of
      neuropathic pain. We suggest that the more rapid sprouting seen after CCI than
      after resection is due to the availability of products of Wallerian degeneration,
      including nerve growth factor, to both spared and regenerating axons following
      CCI, but not following resection.

PMID- 9150302
TI  - Genetic sensitivity to hot-plate nociception in DBA/2J and C57BL/6J inbred mouse
      strains: possible sex-specific mediation by delta2-opioid receptors.
AB  - The inbred mouse strains, DBA/2J (D2) and C57BL/6J (B6), display differential
      sensitivity to acute, thermal nociception as measured on the hot-plate (HP)
      assay. In an ongoing quantitative trait locus (QTL) mapping study designed to
      reveal genomic loci showing genetic linkage to HP sensitivity, a putative QTL on
      chromosome 4 (50-80 cM from the centromere) has been identified that appears to
      account for variability in this trait in male, but not female mice. An obvious
      candidate gene located in this same chromosomal region is Oprd1, which encodes
      the murine delta-opioid receptor. In an attempt to evaluate whether Oprd1
      represents this sex-specific QTL for HP sensitivity, we tested D2 and B6 mice of
      both sexes for HP latencies (hindpaw-lift, -lick or -flutter) following systemic
      injections of saline, or the opioid receptor antagonists naloxone (NAL; 0.1 and
      10 mg/kg), nor-binaltorphimine (nor-BNI; 5 mg/kg), naltrindole (NTI; 5 mg/kg), 7
      benzylidenenaltrexone (BNTX; 0.7 mg/kg), or naltriben (NTB; 1 mg/kg). High-dose
      (10 mg/kg) NAL lowered HP latencies in D2, but not B6 mice, suggesting that the
      higher HP latencies exhibited by D2 mice reflect opioid mechanisms. HP latencies
      in both strains and both sexes were unaffected by pretreatment with low-dose (0.1
      mg/kg) NAL or nor-BNI, suggesting that neither mu nor kappa receptors affect
      basal nociceptive sensitivity. The delta-receptor antagonist, NTI, and the delta2
      specific antagonist, NTB, (but not the delta1-specific antagonist, BNTX)
      effectively lowered HP latencies in a strain- and sex-dependent manner: D2 male >
      B6 male > D2 female > B6 female. These data support the possibility that Oprd1 is
      a QTL mediating HP sensitivity in mice, and more generally illustrate the
      important roles of genetic background and gender in the perception of pain.

PMID- 9150303
TI  - Attenuation of formalin pain responses in the rat by adrenal medullary
      transplants in the spinal subarachnoid space.
AB  - Previous reports have indicated that the implantation of adrenal medullary
      chromaffin cells into the spinal subarachnoid space can reduce both acute and
      chronic pain in several animal models. Recent findings suggest that acute and
      chronic pain alleviation may be mediated by distinct mechanisms. Since the
      formalin response is composed of an acute and tonic phase which can be
      pharmacologically distinguished, the ability of adrenal medullary implants to
      alter these responses was assessed. In rats with adrenal medullary transplants,
      both phases of the formalin response were attenuated, in contrast to control
      implanted animals. Suppression of the acute phase by adrenal medullary implants
      was reversed by the opiate antagonist naloxone, and partially reversed by the
      alpha-adrenergic antagonist phentolamine, suggesting that opioid peptides and
      catecholamines released by the implanted chromaffin cells contribute to the
      observed antinociception. However, neither antagonist altered the antinociceptive
      effects of adrenal medullary implants on the tonic phase of the formalin
      response. These results indicate that adrenal medullary implants in the spinal
      subarachnoid space alleviate acute and tonic pain via distinct pharmacologic
      mechanisms.

PMID- 9150304
TI  - Comments on De Benedittis and Lorenzetti: on topical aspirin/diethyl ether for
      postherpetic neuralgia, PAIN, 65 (1996) 45-51.

PMID- 9150305
TI  - Intravenous morphine-6-glucuronide (M6G) is devoid of analgesic activity in man.

PMID- 9150307
TI  - Comments on Richardson, PAIN, 65 (1996) 277-278.

PMID- 9150306
TI  - Comments on Kramis, Roberts and Gillette, PAIN, 67 (1996) 209-229.

PMID- 9150308
TI  - Reply to Sarantopoulos and Fassoulaki, PAIN, 65 (1996) 273-276.

PMID- 9150309
TI  - Comments on Anand and Craig, PAIN, 67 (1996) 3-6.

PMID- 9150310
TI  - Bias toward use of T-cell receptor variable regions in the lung: research tool or
      clinically useful technique?

PMID- 9150311
TI  - Leukocyte migration and activation in the lungs.

PMID- 9150312
TI  - Lung and blood T-cell receptor repertoire in extrinsic allergic alveolitis.
AB  - Patients with extrinsic allergic alveolitis (EAA) have accumulations of T
      lymphocytes in their lungs. CD8+ lung T-cells, in particular, have been
      implicated in the pathogenesis of EAA. The objective of the present study was to
      analyse the T-cell receptor (TCR) V alpha and V beta gene usage of CD4+ and CD8+
      lung and peripheral blood lymphocytes (PBLs) before and after treatment. Twelve
      patients with clinical signs of extrinsic allergic alveolitis were studied at
      disease onset, and nine of the 12 were also studied after treatment and clinical
      recovery. Lung cells, obtained by bronchoalveolar lavage (BAL), and paired PBL
      samples were analysed by flow cytometry using a panel of anti-TCR V monoclonal
      antibodies. The changes in TCR V gene usage were most pronounced in BAL CD8+
      cells, as compared to the BAL CD4+, PBL CD8+ and PBL CD4+ subsets. At disease
      onset, 10 of the 12 patients had lung restricted expansions of CD8+ T-cells using
      a particular V alpha or V beta gene segment, and 8 of the 12 patients had CD8+ T
      cell expansions in PBL. For the patients in whom a follow-up was possible, a
      majority of the expansions in the lungs were normalized, whereas most of the
      expansions in PBL remained. An over-representation of human leucocyte antigen
      (HLA)-DR2 (15) was detected, particularly among patients with farmer's lung. An
      increased selected T-cell receptor V gene usage may follow specific interactions
      between T-cells and antigens. In extrinsic allergic alveolitis, we determined
      that such expansions occur most frequently in the lung CD8+ T-cells. Since most
      expansions of lung CD8+ T-cells normalized with clinical improvement, these are
      further implicated in the pathogenesis of extrinsic allergic alveolitis.

PMID- 9150313
TI  - High prevalence of mollusc shell hypersensitivity pneumonitis in nacre factory
      workers.
AB  - Following the discovery of hypersensitivity pneumonitis caused by the inhalation
      of mollusc shell dust in two workers from a nacre-button factory, the health
      status of 26 workers employed in sawing mollusc shells was investigated. The
      evaluation included the administration of two questionnaires and radiological,
      functional and immunological assessments of all workers at the outset and 1 year
      later, when hygienic and therapeutic measures had been taken. Six workers, in
      whom specific inhalation challenge test was positive, were diagnosed with mollusc
      shell hypersensitivity pneumonitis, thus yielding a prevalence of 23%. Evidence
      of diffuse lung disease and systemic symptoms was found in these patients.
      Nonspecific bronchial hyperreactivity was also found more frequently in patients
      with mollusc shell hypersensitivity pneumonitis. Specific immunoglobulin G (IgG)
      level and specific skin testing failed to differentiate patients with mollusc
      shell hypersensitivity pneumonitis from other exposed workers; whereas,
      nonspecific skin testing, which was impaired in the patients, did differentiate.
      Bronchoalveolar lavage and transbronchial biopsy performed in patients with
      mollusc shell hypersensitivity pneumonitis were consistent with the disease.
      Removal from an environment containing mollusc shell dust was followed by
      regression of clinical, radiological and functional changes. The clinical picture
      of the 20 workers who did not present mollusc shell hypersensitivity pneumonitis
      remained unchanged, but functional decline was observed despite improvement in
      the environmental conditions of the factory. This report describes the first
      series of patients with mollusc shell hypersensitivity pneumonitis studied, and
      underlines the importance of careful follow-up of workers occupationally-exposed
      to mollusc shell dust.

PMID- 9150314
TI  - Altered accessory cell function of alveolar macrophages: a possible mechanism for
      induction of Th2 secretory profile in idiopathic pulmonary fibrosis.
AB  - Alveolar macrophages (AMs) are considered to play a central role in the
      pathogenesis of idiopathic pulmonary fibrosis (IPF). Recent studies have revealed
      a predominance of the type-2 T-helper (Th2) cytokine pattern of inflammatory
      response in the pulmonary interstitium in IPF. The aim of the present study was
      to determine whether or not the altered accessory cell function of AMs could
      account for the Th2 pattern of chronic inflammation in IPF. The levels of various
      cytokines were measured in the supernatants of soluble anti-CD3 monoclonal
      antibody (MoAb)-stimulated T-cells, co-cultured with autologous AMs, by enzyme
      linked immunosorbent assay (ELISA). Cells from six patients with IPF and from
      nine normal volunteers (five nonsmokers and four smokers) were examined. The
      inhibitory effect of interleukin (IL)-10 on the accessory cell function of AMs
      and the expression of CD80 and CD86 on AMs were also investigated. IL-4 and IL-5
      levels were significantly higher in the co-cultures from patients with IPF than
      in those from normal volunteers. IL-2, interferon-gamma (IFN-gamma), and IL-10
      production in these co-cultures did not differ. IL-10 suppressed T-cell
      proliferation in co-cultures with AMs from healthy volunteers (smokers and
      nonsmokers), but not with AMs from patients with IPF. Expression of CD80 and CD86
      on AMs from these groups did not differ. Thus, the altered accessory cell
      function of alveolar macrophages from patients with idiopathic pulmonary fibrosis
      may possibly relate to the pattern of type-2 T-helper cytokine production in
      response to inflammation.

PMID- 9150315
TI  - Dissociation of neutrophil emigration and metabolic activity in lobar pneumonia
      and bronchiectasis.
AB  - In animal models of pulmonary inflammation, neutrophils exhibit a dramatic influx
      of glucose in periods of high metabolic activity. This information was utilized
      to develop a technique, involving positron emission tomography (PET) of 2-[18F]
      fluoro-2-deoxy-D-glucose (18FDG), which measures neutrophil activity in situ.
      This technique was applied in a comparative study of neutrophil function in
      patients with acute lobar pneumonia or bronchiectasis. Neutrophil emigration was
      measured by gamma-scintigraphy of intravenously injected 111In-labelled
      granulocytes and neutrophil activity determined by PET of 18FDG. Neutrophil
      emigration was evident in 4 out of 5 bronchiectasis patients, whilst no
      emigration was apparent in the two pneumonia patients studied, consistent with
      animal studies showing maximum emigration soon after challenge. In contrast,
      18FDG uptake was markedly increased in 4 out of 5 pneumonia patients but not in
      the patients with bronchiectasis. Localization of radioactivity to neutrophils
      was confirmed by microautoradiography of lavage fluid in a patient with
      pneumonia. These results suggest that the elevated uptake of glucose by
      neutrophils during the inflammatory response is a postmigratory event, most
      likely reflecting the respiratory burst, and that high levels of neutrophil
      emigration are not necessarily associated with significantly increased metabolic
      activity of these cells.

PMID- 9150316
TI  - The binding of surface proteins from Staphylococcus aureus to human bronchial
      mucins.
AB  - Colonization by Staphylococcus aureus is frequently observed in obstructive lung
      diseases, particularly in cystic fibrosis. It has been shown that the bacteria
      bind to mucins, the main constituent of bronchial secretions. The binding
      mechanism, however, remains unclear. We have investigated the interactions of two
      strains of S. aureus, one mucoid and one nonmucoid, with human bronchial mucins.
      Using a solution phase assay, the binding capacity of the two strains to
      radiolabelled bronchial mucins was assessed. The bacterial constituents were
      released by lysostaphin lysis and the surface components of the nonmucoid strain
      were extracted with the use of a detergent (3-([3-cholamidopropyl]
      dimethylammonio)-1-propane sulphonate (CHAPS)). All were analysed for mucin
      binding using an overlay assay. The amount of mucins bound to the nonmucoid
      strain was threefold greater than that of the mucoid strain. In the lysostaphin
      extract from the mucoid strain, only a 57 kDa protein faintly bound 125I-labelled
      mucins, whereas three mucin-binding proteins (52, 57 and 71 kDa) were identified
      from the nonmucoid strain. Two surface proteins, one major at 60 kDa and one
      minor at 71 kDa, bound radiolabelled bronchial mucins and their binding was
      almost completely inhibited by ovine submaxillary mucin. These results indicate:
      1) differences in the mucin-binding capacity from one strain of S. aureus to
      another; and 2) the presence of external and internal adhesins binding to human
      respiratory mucins in the nonmucoid strain.

PMID- 9150317
TI  - Value of fibreoptic bronchoscopy in the diagnosis of complicated pulmonary
      unilocular cystic hydatidosis.
AB  - Complicated pulmonary unilocular cystic hydatidosis (CPUCH) is a serious
      condition, which requires immediate treatment. The aim of the present study was
      to evaluate the efficacy of fibreoptic bronchoscopy (FOB) in the final diagnosis
      of CPUCH. Of 1,726 cases, who underwent FOB evaluation between 1990 and 1994 in
      our centre, 24 patients (17 females and 7 males), who had proven CPUCH after
      thoracotomy, were included in this study. Fourteen of the 24 cases were diagnosed
      in the preoperative period by cytological and histopathological evaluation of FOB
      material, whereas the remaining 10 cases with presumed CPUCH underwent
      thoracotomy for final diagnosis. Of the 14 cases diagnosed by FOB (11 females and
      3 males); none had concomitant extrapulmonary hydatid disease. Whitish-yellow
      membranes were seen in 12 of the cases during FOB. Whilst cuticular particles,
      degenerated scoleces, and hooklets were seen in 14 cases in bronchial lavage,
      these elements were identified in brushing material in only seven. In 10 of the
      14 cases, cytological diagnosis was confirmed by FOB biopsies before thoracotomy.
      It is concluded that whilst the clinical, radiological and laboratory findings
      are presumptive, fibreoptic bronchoscopic examination and the cytological and
      histopathological examination of material obtained during that procedure are
      conclusive for the diagnosis of complicated pulmonary unilocular cystic
      hydatidosis.

PMID- 9150318
TI  - An evaluation of salmeterol in the treatment of chronic obstructive pulmonary
      disease (COPD)
AB  - The objectives of this study were to compare the efficacy and safety of
      salmeterol xinafoate (50 and 100 microg b.i.d.) with that of placebo, when added
      to existing therapy, in the treatment of patients with chronic obstructive
      pulmonary disease (COPD). Six hundred and seventy four patients were randomized
      to receive either salmeterol 50 microg b.i.d., salmeterol 100 microg b.i.d., or
      placebo treatment for a period of 16 weeks. The results showed a significant
      improvement in daily symptom scores noted for patients taking either 50 microg
      (p=0.043) or 100 microg b.i.d. salmeterol (p=0.01) compared with placebo, with a
      corresponding decrease in additional daytime salbutamol requirements for both
      salmeterol groups. The same pattern was reflected for night-time symptoms and
      additional salbutamol use. During treatment, forced expiratory volume in one
      second (FEV1) measurements improved significantly in each salmeterol group, with
      up to a 7% improvement observed at the end of the study. Although no difference
      was observed between treatment groups for the distance walked in 6 min, patients
      treated with salmeterol 50 microg b.i.d. were significantly less breathless than
      those treated with placebo after their 6 min walk, after 8 weeks (p=0.024) and 16
      weeks (p=0.004) of therapy. Adverse events were similar in all three groups
      except for tremor, which was significantly higher in the 100 microg b.i.d.
      salmeterol group (p=0.005) compared both with 50 microg b.i.d. salmeterol and
      placebo. Salmeterol offered further positive improvement to the effect of therapy
      in patients with chronic obstructive pulmonary disease when added to their
      existing regimens. This clinical improvement was similar both with 50 and 100
      microg b.i.d. dosage, although the group receiving 50 microg b.i.d. tolerated the
      drug better than those receiving 100 microg b.i.d. salmeterol.

PMID- 9150319
TI  - Gender difference in smoking effects on lung function and risk of hospitalization
      for COPD: results from a Danish longitudinal population study.
AB  - Recent findings suggest that females may be more susceptible than males to the
      deleterious influence of tobacco smoking in developing chronic obstructive
      pulmonary disease (COPD). This paper studies the interaction of gender and
      smoking on development of COPD as assessed by lung function and hospital
      admission. A total of 13,897 subjects, born after 1920, from two population
      studies, 9,083 from the Copenhagen City Heart Study (CCHS) and 4,814 from the
      Glostrup Population Studies (GPS), were followed for 7-16 yrs. Data were linked
      with information on hospital admissions caused by COPD. Based on cross-sectional
      data, in the CCHS the estimated excess loss of forced expiratory volume in one
      second (FEV1) per pack-year of smoking was 7.4 mL in female smokers who inhaled
      and 6.3 mL in male smokers who inhaled. In the GPS, the corresponding excess loss
      of FEV1 was 10.5 and 8.4 mL in females and males, respectively. Two hundred and
      eighteen subjects in the CCHS and 23 in the GPS were hospitalized during follow
      up. Risk associated with pack-years was higher in females than in males (relative
      risks (RRs) for 1-20, 20-40 and >40 pack-years were 7.0 (3.5-14.1), 9.8 (4.9
      19.6) and 23.3 (10.7-50.9) in females, and 3.2 (1.1-9.1), 5.7 (2.2-14.3) and 8.4
      (3.3-21.6) in males) but the interaction term gender x pack-years did not reach
      significance (p=0.08). Results were similar in the GPS. After adjusting for
      smoking in more detail, females in both cohorts had an increased risk of
      hospitalization for COPD compared to males with a RR of 1.5 (1.2-2.1) in the CCHS
      and 3.6 (1.4-9.0) in the GPS. This was not likely to be caused by a generally
      increased rate of hospital admission for females. Results were similar when
      including deaths from COPD as endpoint. In two independent population samples,
      smoking had greater impact on the lung function of females than males, and after
      adjusting for smoking females subsequently suffered a higher risk of being
      admitted to hospital for COPD. Results suggest that adverse effects of smoking on
      lung function may be greater in females than in males.

PMID- 9150320
TI  - Transtracheal oxygen therapy: an effective and safe alternative to nasal oxygen
      administration.
AB  - Transtracheal oxygen therapy (TTOT) improves the efficiency of oxygen delivery
      and overcomes the discomfort associated with nasal oxygen delivery in patients on
      long-term oxygen therapy (LTOT). In addition, TTOT improves compliance and
      quality of life, and may reduce morbidity. Experience with TTOT in Europe is,
      however, scarce and the safety of TTOT has not yet been completely determined.
      These were reasons for testing the acceptance, efficacy and safety of TTOT.
      Patients were selected on the basis of the accepted indications and
      contraindications for TTOT. In 75 patients (48 males and 27 females) the mean
      follow-up time was 16 (range 0.5-51.5) months. Compared to nasal cannulae, TTOT
      caused a reduction in the oxygen flow rate of 47 (33-60)% at rest and a
      significant increase in the number of hours that oxygen was used. All patients on
      TTOT used oxygen for at least 20 h x day(-1). Most patients saw the procedure as
      a minor intervention. It was usually performed on an out-patient basis. In 34
      patients, 51 mainly minor complications were seen, and most of these occurred in
      the first 10 patients. After precautions had been taken, complications occurred
      less frequently. No patient needed to be hospitalized because of a complication.
      TTOT had to be stopped in two patients; nevertheless, all patients preferred TTOT
      to the nasal cannulae. We conclude that transtracheal oxygen therapy is an
      effective and safe alternative to nasal oxygen administration, provided that it
      is restricted to a well-defined group of patients and applied by a motivated and
      experienced group of physicians.

PMID- 9150321
TI  - Effect of corticosteroids on release of RANTES and sICAM-1 from cultured human
      bronchial epithelial cells, induced by TNF-alpha.
AB  - We have recently demonstrated that human bronchial epithelial cells can
      synthesise and release several inflammatory mediators, including the factor
      regulated on activation, normal T-cell expressed and secreted (RANTES) and
      soluble intercellular adhesion molecule-1 (sICAM-1), which influence the activity
      of eosinophils, and may, therefore play a role in the aetiology of asthma. In
      this study we investigated whether corticosteroids could influence the release of
      these proinflammatory mediators from human bronchial epithelial cells. Human
      bronchial epithelial cells were cultured to confluence as explant cultures, and
      incubated in the presence of 50 ng x mL(-1) tumour necrosis factor-alpha (TNF
      alpha) +/- 0-10(-4) M of either fluticasone propionate (FP), beclomethasone
      dipropionate (BDP), or hydrocortisone (HC) for 24 h. The culture medium was
      collected and analyzed for RANTES and sICAM-1, by enzyme-linked immunosorbent
      assay (ELISA), and the cells were analysed for total protein. The TNF-alpha
      significantly increased the release both of RANTES and sICAM-1 (63.0 fg RANTES x
      microg(-1) protein; p<0.05; 8.8 pg sICAM-1 x microg(-1) protein; p<0.02), when
      compared with untreated cells (10.3 fg RANTES x microg(-1) protein; 2.6 pg sICAM
      1 x microg(-1) cellular protein). The TNF-alpha-induced release both of RANTES
      and sICAM-1 occurred in a time-dependent manner, and was maximal by 24 h
      incubation. FP 10(-6)-10(-4) M significantly attenuated the TNF-alpha-induced
      release both of RANTES and sICAM-1. In contrast, 10(-4) M BDP or HC significantly
      attenuated the release of only sICAM-1. These results suggest that
      corticosteroids may prevent airway inflammation by downregulating the synthesis
      and/or release of proinflammatory mediators from bronchial epithelial cells.
      Furthermore, fluticasone propionate may be more efficacious than beclomethasone
      dipropionate or hydrocortisone in this respect.

PMID- 9150322
TI  - Effects of two weeks of topical budesonide treatment on microvascular exudative
      responsiveness in healthy human nasal airways.
AB  - Extravasation and luminal entry of plasma (mucosal exudation) is not only a key
      feature of airway inflammation in rhinitis and asthma but also a major first-line
      respiratory defence mechanism. Topical steroids are effective antiexudative
      agents in disease but, so far, little is known about the direct effects of these
      drugs on the responsiveness of the microcirculation in human airways. In this
      study, the effects of prolonged budesonide treatment on histamine-induced mucosal
      exudation of plasma was examined in 42 healthy subjects. Placebo and budesonide
      (100 microg per nasal cavity b.i.d.) were given for 2 weeks in a double-blind and
      placebo-controlled parallel-group protocol. Using a nasal pool technique, nasal
      challenges with isotonic saline and histamine (40 and 400 microg x mL(-1)) were
      carried out before and late in the treatment periods. The lavage fluid levels of
      alpha2-macroglobulin were measured as an index of mucosal exudation of bulk
      plasma. Histamine produced concentration-dependent mucosal exudation of plasma
      before as well as after treatment with either placebo or budesonide. The topical
      steroid treatment only marginally (1.8 fold) decreased the response to the low
      concentration histamine (40 microg x mL(-1)) and, although it was significantly
      (2.8 fold) reduced, histamine 400 microg x mL(-1) still produced significant
      mucosal exudation of plasma in the budesonide group. If the present observations
      are extrapolated to inflammatory conditions, the antiexudative effects of topical
      steroids in rhinitis (and asthma) may reflect only a small degree of
      microvascular antipermeability effects. We suggest that topical steroid treatment
      may not impede mucosal exudation responses when called for in acute human airway
      defence reactions.

PMID- 9150323
TI  - Increased bronchoalveolar granulocytes and granulocyte/macrophage colony
      stimulating factor during exacerbations of chronic bronchitis.
AB  - Although inflammatory changes are found throughout the airways of patients with
      chronic bronchitis, the mechanisms of the pathogenesis of chronic bronchitis are
      still unclear. The aim of this study was to investigate airways inflammation in
      patients with and without an exacerbation of bronchitis. Thirteen chronic
      bronchitic patients and nine normal subjects were studied. Eight of the patients
      were studied under baseline conditions (B), and five during an exacerbation of
      bronchitis (E). Bronchoscopy and bronchoalveolar lavage (BAL) with cytological
      analysis were performed, and the levels of granulocyte/macrophage colony
      stimulating factor (GM-CSF) were determined in sera and in BAL supernatants by a
      solid phase enzyme immunoassay. Compared with patients under baseline conditions,
      chronic bronchitic patients with an exacerbation had increased numbers of BAL
      neutrophils (10+/-3 and 83+/-18x10(3) cells x mL(-1), respectively; p<0.0001) and
      of BAL eosinophils (1.9+/-0.5 and 6.7/-1.9x10(3) cells x mL(-1), respectively;
      p=0.014). Patients with chronic bronchitis, as a whole, had significantly
      increased levels of BAL GM-CSF compared to control subjects (36+/-5 and 19+/-4 pg
      x mL(-1), respectively; p=0.035), and similar levels of serum GM-CSF. Serum
      levels of GM-CSF were markedly increased in chronic bronchitic patients with an
      exacerbation, as compared with patients under baseline conditions (1.4+/-0.4 and
      13+/-1 pg x mL(-1), respectively; p <0.0001). BAL levels of GM-CSF were also
      increased in chronic bronchitic patients with an exacerbation (25+/-5 and 54+/-8
      pg x mL(-1), respectively; p=0.009). During exacerbations of chronic bronchitis
      there are changes in the cell populations in bronchoalveolar lavage of patients
      consistent with a recruitment of polymorphonuclear leucocytes in the airway
      lumen. The increased levels of granulocyte/macrophage colony-stimulating factor
      might suggest a role for this cytokine in the inflammatory processes of chronic
      bronchitis.

PMID- 9150324
TI  - The effect of nedocromil sodium on human airway epithelial cell-induced
      eosinophil chemotaxis and adherence to human endothelial cell in vitro.
AB  - Although some studies have shown that long-term treatment of asthmatics with
      nedocromil sodium can reduce airway hyperresponsiveness and improve symptoms and
      lung function, the mechanisms underlying its effects are not well understood. We
      have investigated the effect of nedocromil sodium on eosinophil chemotaxis,
      eosinophil adherence to human endothelial cells and release of soluble
      intercellular adhesion molecule-1 (sICAM-1) from endothelial cells, induced by
      conditioned medium collected from cultured human bronchial epithelial cells.
      Conditioned medium significantly increased eosinophil chemotaxis from a baseline
      median value of 2.1 (range 1.9-4.5) cells-high power field(-1) (HPF) to 10.5
      (range 7.8-12.3) cells-HPF(-1) (p<0.05). Similarly, conditioned medium
      significantly increased eosinophil adherence to endothelial cells from a baseline
      value of 9 (range 8-12)% to 23 (range 21-30)% (p<0.05). Nedocromil sodium, at 10(
      5) M concentration, significantly attenuated the eosinophil chemotaxis and
      adherence induced by conditioned medium. Conditioned medium also significantly
      increased the release of sICAM-1 from endothelial cells, from a baseline value of
      11.5 (range 8.1-15.4) pg x microg(-1) protein to 67.6 (range 55.6-73.5) pg x
      microg(-1) protein (p<0.05). This was significantly attenuated by anti-tumour
      necrosis factor-alpha (TNF-alpha), anti-interleukin-1beta (IL-1beta) and 10(-5) M
      nedocromil sodium. These findings suggest that human bronchial epithelial cell
      derived mediators may potentiate eosinophil activity, and that this can be
      modulated by nedocromil sodium, suggesting a possible mechanism underlying its
      anti-inflammatory effect.

PMID- 9150325
TI  - The effect of inhaled sodium cromoglycate on cellular infiltration into the
      bronchial mucosa and the expression of adhesion molecules in asthmatics.
AB  - There is no direct evidence of the anti-inflammatory effect of inhaled sodium
      cromoglycate (SCG). To investigate whether inhaled SCG has any effect on cellular
      infiltration into the bronchial mucosa and the expression of adhesion molecules
      in patients with asthma, biopsies of the bronchial mucosa were taken from nine
      patients with atopic bronchial asthma before and after treatment with inhaled SCG
      (8 mg x day(-1)) from a metered-dose inhaler (MDI). Eosinophils were stained with
      anti-EG2, neutrophils with anti-NP57, mast cells with anti-AA1, T-lymphocytes
      with anti-CD4, CD8 and CD3, and macrophages with anti-CD68. Intercellular
      adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1),
      endothelial leucocyte adhesion molecule-1 (ELAM-1) and P-selectin were stained at
      the same time as adhesion molecules expressed in vascular endothelium. The
      intensity of ICAM-1 expression in the bronchial epithelium was also evaluated.
      The numbers of eosinophils, mast cells, T-lymphocytes and macrophages were
      significantly reduced as a result of SCG administration, and the expression of
      ICAM-1, VCAM-1 and ELAM-1 was also significantly inhibited. A significant
      correlation was found between ICAM-1 expression and T-lymphocytes and between
      VCAM-1 expression and eosinophils. It was concluded that sodium cromoglycate does
      have an effect on the infiltration of the bronchial mucosa by inflammatory cells
      and also on the expression of adhesion molecules.

PMID- 9150327
TI  - Short-term effects of particulate air pollution on respiratory morbidity in
      asthmatic children.
AB  - Short-term effects of air pollution (consisting primarily of sulphur dioxide and
      particulate matter but with low acidity) on respiratory morbidity were studied in
      asthmatic children from Sokolov, Czech Republic. Eighty nine children with
      asthma, who recorded daily peak expiratory flow measurements, symptoms and
      medication use in a diary, were analysed for 7 months during the winter of 1991
      1992. Air pollution measurements included: SO2, total suspended particulates
      (TSPs), inhalable particles, ie. particulate matter of aerodynamic diameter < or
      = 10 microm, particle strong acidity (PSA) and fine particle sulphate
      concentration (SO4). Linear and logistic regression analyses estimated the impact
      of air pollutants adjusted for trend, temperature and weekend and autocorrelated
      errors. Exposure to elevated levels of air pollution was associated with
      decreased peak expiratory flow rates, increased respiratory symptoms, increased
      prevalence of school absence and fever, and increased medication use. Prolonged
      exposure to particle SO4 showed the largest effect estimates. At the end of
      January, an air pollution episode occurred, during which respiratory symptoms,
      prevalence of fever, school absence and asthma medication increased. The
      association between respiratory symptoms and particulate SO4 was highly dependent
      on this episode, whilst the associations between lung function and SO4 as well as
      between fever and SO4 were still observed when this air pollution episode was
      excluded. Some evidence was found that exposure to air pollution might have
      enhanced the respiratory symptoms while children were experiencing respiratory
      infections. In this study, a panel of children with mild asthma experienced small
      decreases in peak expiratory flow and increased dyspnoea in association with fine
      particles formed during air pollution episodes.

PMID- 9150326
TI  - Activity of inhaled lysine acetylsalicylate (L-ASA) on bradykinin-induced
      bronchoconstriction in asthmatics: evidence of contribution of prostaglandins.
AB  - When administered by inhalation, bradykinin provokes dose-related
      bronchoconstriction in asthmatic subjects by a mechanism believed to involve
      activation of sensory nerve endings. However, little is known of the change in
      airway responsiveness to bradykinin after cyclo-oxygenase blockade. The aim of
      the present study was to investigate the effect of the potent cyclo-oxygenase
      inhibitor, lysine acetylsalicylate (L-ASA), administered by inhalation, on
      bradykinin-induced bronchoconstriction in a group of 12 asthmatic subjects. The
      subjects attended the laboratory on four separate occasions to receive nebulized
      L-ASA (solution of 90 mg x mL(-1)) or matched placebo (glycine, solution of 30 mg
      x mL(-1)) 15 min prior to bronchoprovocation tests with bradykinin and
      methacholine in a randomized, double-blind order with at least a 5 day interval.
      Changes in airway calibre were followed as forced expiratory volume in one second
      (FEV1), and responsiveness to agonists was expressed as the provocative
      concentration causing a 20% fall in FEV1 from baseline (PC20). Administration
      both of L-ASA and glycine solution caused a small but significant acute fall in
      FEV1 from baseline, with gradual recovery within 20 min. When compared to
      placebo, inhaled L-ASA reduced the airway responsiveness to bradykinin in 11 of
      the 12 subjects studied, the geometric mean (range) values for PC20 bradykinin
      increasing significantly (p<0.001) by 1.7 doubling dose from 0.55 (0.11-5.05) to
      1.72 (0.26-6.05) mg x mL(-1) after placebo and L-ASA, respectively. No
      significant change in airway responsiveness to methacholine was recorded after L
      ASA. It is concluded that administration of lysine acetylsalicylate by inhalation
      protects the asthmatic airways against bradykinin-induced bronchoconstriction,
      thus suggesting that endogenous prostaglandins may play a contributory role in
      the bronchoconstriction to kinins in human asthma.

PMID- 9150328
TI  - Lung function and airway responsiveness in children and adolescents after hyaline
      membrane disease: a matched cohort study.
AB  - Some investigators consider prematurity to be responsible for the lung function
      abnormalities found in prematurely born children and adolescents who had neonatal
      respiratory diseases. This study attempts to measure the effect of neonatal
      respiratory disease on lung function during school age and adolescence, by
      controlling the confounding effect due to prematurity. Lung volumes, airway
      resistance and specific airway conductance measured by plethysmography, maximum
      expiratory flow-volume curves, pulmonary diffusion of carbon monoxide, and the
      airway responsiveness to a challenge with methacholine, were determined in a
      cohort of children aged 8-14 yrs, who had suffered from hyaline membrane disease
      but who did not develop bronchopulmonary dysplasia. The values obtained were
      compared with those of children without hyaline membrane disease, not ventilated
      for other causes, and matched for gestational age, sex and age. Thirty six pairs
      of children were enrolled, of which 26 participated in the methacholine test.
      Compared to their paired controls, children with hyaline membrane disease had a
      significantly lower forced expiratory volume in one second (FEV1), forced mid
      expiratory flow (FEF25-75), and maximal expiratory flow when 75, 50 and 25% of
      the forced vital capacity remained in the lung (MEF75, MEF50 and MEF25,
      respectively), and a significantly higher airway resistance (Raw). The effect was
      less in children born more prematurely, who showed less difference in FEF25-75,
      MEF75 and MEF25. The duration of treatment with steroids in the neonatal period
      was associated with a reduction in the differences in FEV1, MEF25 and Raw.
      Independent of prematurity, hyaline membrane disease and its treatment is
      associated with alterations in long-term lung function, even in children who do
      not develop bronchopulmonary dysplasia. The effect can be less in more premature
      children, and neonatal steroids can have a long-term preventive effect.

PMID- 9150329
TI  - Ureaplasma urealyticum colonization, prematurity and bronchopulmonary dysplasia.
AB  - The aim of the present study was to determine the association between the
      presence of Ureaplasma urealyticum in endotracheal aspirates and bronchopulmonary
      dysplasia (BPD). In addition, a review of similar studies from the English
      literature is presented. During the period February 1990 until March 1991, 108
      mechanically-ventilated infants were included in a prospective study.
      Endotracheal aspirates were cultured for U. urealyticum. Birth weight,
      gestational age and development of BPD was recorded. Cultures were positive in 23
      infants, resulting in a 21% colonization. The infants with positive cultures had
      a significantly lower gestational age (mean 28.9 vs 31.5 weeks; range 25-40 vs 25
      42 weeks; p=0.0014). A positive U. urealyticum culture was not associated with a
      low birth weight (mean 1,390 vs 1,690 g; range 675-4,090 vs 700-3,600 g;
      p=0.0712). A positive U. urealyticum culture was significantly associated with
      BPD (p=0.0373). However, after correction for gestational age by logistic
      regression analysis, BPD failed to correlate with the presence of positive U.
      urealyticum cultures. A MEDLINE search of the English language literature was
      performed to identify all studies having the association of U. urealyticum
      colonization and BPD. Fourteen controlled studies were found. Five studies found
      no significant association between U. urealyticum colonization and BPD. In two
      studies, after correction for gestational age, the association between U.
      urealyticum colonization and BPD did not remain significant. In five studies with
      a significant association between U. urealyticum colonization and BPD, no
      correction for gestational age had taken place. In conclusion, U. urealyticum
      colonization is not associated with the development of bronchopulmonary
      dysplasia. U. urealyticum is often associated with gestational age and/or low
      birth weight; to investigate the association between U. urealyticum and
      bronchopulmonary dysplasia correction for both parameters should be made.

PMID- 9150330
TI  - Respiratory resistance by the forced oscillation technique in asthmatic children
      and cystic fibrosis patients.
AB  - Measurement of the total resistance of the respiratory system (Rrs) is an
      attractive alternative to measurement of forced expiratory volume in one second
      (FEV1) in young children because it requires minimal co-operation. The purpose of
      this study was to assess the ability of the forced oscillation technique (FOT) to
      detect airway obstruction in asthmatic children and in patients with cystic
      fibrosis (CF). Spirometry and Rrs were recorded in 45 asthmatic children (32
      males and 13 females) and in 45 patients with CF (28 males and 17 females). Rrs
      was measured at 10 Hz with the Siregnost FD5 (Siemens, Germany). The asthmatic
      children were slightly younger than the patients with CF (10+/-3 vs 14+/-7 yrs),
      and had milder airway obstruction (FEV1 80+/-19 vs 66+/-27% of predicted). Rrs
      was significantly higher in the asthmatic children (6.6+/-1.7 cmH2O x L(-1) x s)
      than in the patients with CF (4.8+/-1.4 cmH2O x L(-1) x s). A normal FEV1 (> or =
      mean -2SD) was associated with a normal Rrs (< or = mean +2SD) in 17 of the 45
      asthmatic children and in 13 of the 45 CF patients. By contrast, a low FEV1 (<
      mean -2SD) was associated with an increased Rrs (> mean +2SD) in 21 of the 45
      asthmatic children, but in only 3 of the 45 CF patients. Thus, FEV1 and Rrs
      yielded concordant information in asthmatic children much more often (38 out of
      45) than in CF patients (16 out of 45) (p < 0.001). In CF, Rrs failed to detect
      even severe airways obstruction. These findings might be accounted for by the
      inability of Rrs to reflect peripheral obstruction. We conclude that total
      respiratory resistance is suitable to assess airways obstruction in asthmatic
      children but not in cystic fibrosis patients.

PMID- 9150331
TI  - Home intravenous therapy in cystic fibrosis: a prospective randomized trial
      examining clinical, quality of life and cost aspects.
AB  - In this study, we set out to determine if home intravenous (i.v.) antibiotic
      therapy in adult patients with cystic fibrosis (CF) is a feasible, effective and
      less costly alternative to hospitalization, and to assess the impact of home
      therapy on quality of life. The study was a prospective, randomized, two-factor
      mixed design involving adults presenting with respiratory exacerbations of CF.
      Patients were randomized such that they were discharged home after 2-4 days, or
      remained in hospital. Seventeen patients had 31 admissions (13 home and 18
      hospital). Following 10 days of therapy, there were no significant differences
      between home or hospital arms with respect to body weight, 12 minute walking
      distance, sputum weight, pulse oximetry, or improvement in lung function (forced
      expiratory volume in one second (FEV1), or forced vital capacity (FVC)). Patients
      who remained in hospital were less fatigued and noted a greater degree of
      mastery. Patients discharged early noted less disruption to their family life,
      personal life and sleeping pattern. The total cost for the home therapy arm was
      approximately half that of the hospital therapy arm. Home intravenous antibiotic
      therapy in patients with cystic fibrosis was a feasible, cost-effective
      alternative to receiving therapy in hospital. Although there was no clinical
      compromise associated with home therapy, there were advantages and disadvantages
      in terms of quality of life.

PMID- 9150332
TI  - Gas compression artefacts when testing peak expiratory flow meters with
      mechanically-driven syringes.
AB  - Mechanically-driven syringes used to test peak expiratory flow (PEF) meters must
      produce the American Thoracic Society (ATS) standard waveforms with PEF accuracy
      of 2%. However, gas compression within the syringe could result in significant
      PEF inaccuracy when testing high resistance meters. The gas compression artefact
      was investigated in a mechanical syringe (PWG; MH Custom Design & Mfg L.C.,
      Midvale, Ut, USA) of 13.6 L connected to a standard range mini-Wright PEF meter
      (Clement Clarke International, Harlow, UK). Scaled versions of the ATS standard
      waveform No. 24, with peak flows of 750 and 450 L x min(-1), were discharged
      through the PEF meter from different starting piston positions to vary syringe
      volume (Vsyr). The PEF recorded by the meter decreased linearly with increasing
      Vsyr. PEF decreased by 0.31 and 0.27% per litre for the ATS standard waveforms
      with PEF of 750 and 450 L x min(-1), respectively. The target PEF computed from
      piston displacement overread the actual PEF delivered into the PEF meter by
      approximately 4% when Vsyr = 13.6 L. Overreading fell to approximately 1% when
      Vsyr was reduced to 3.62 L. Therefore, gas compression error in commercially
      available large mechanical syringes can exceed the 2% inaccuracy limit when
      testing high resistance portable PEF meters. Measurements can be corrected for
      gas compression by linearly extrapolating PEF recordings to zero volume.

PMID- 9150333
TI  - Comparison of jet and ultrasonic nebulizer pulmonary aerosol deposition during
      mechanical ventilation.
AB  - Increased delivery of aerosol to a model lung (attached to a mechanical
      ventilator) has been demonstrated with an ultrasonic nebulizer as compared to a
      jet nebulizer. This study examined whether the increased aerosol deposition with
      an ultrasonic nebulizer could also be demonstrated in vivo. Seven patients (6
      male and 1 female) were studied during mechanical ventilalion (Siemens Servo
      900C, Middlesex, UK) after open heart surgery. Two studies were performed in each
      patient. In the first study, aerosol was delivered via a Siemens Servo 945
      nebulizer system (high setting) driving a System 22 Acorn jet nebulizer (Medic
      Aid, Sussex, UK) containing 3 mL (99m)technetium-labelled human serum albumin
      (99mTc-HSA) (50 microg; activity 74 MBq). In the second study, a DP100 ultrasonic
      nebulizer (DP Medical, Meylan, France) containing 12 mL 99mTc-HSA (50 microg;
      activity 185 MBq) was used. Pulmonary deposition was quantified using a gamma
      camera. The humidification of the circuit and the ventilator settings were kept
      constant according to the patient's clinical requirements. The total lung aerosol
      deposition (mean+/-SD), as a percentage of initial nebulizer activity, was
      greater using the ultrasonic nebulizer than using the jet nebulizer (53+/-1.4 vs
      2.3+/-0.9%; p<0.002). The ultrasonic nebulizer was also associated with a
      reduction in the time required to complete nebulization (9 vs 21 min,
      respectively) (p<0.0001). Use of the DP100 ultrasonic nebulizer more than doubled
      lung deposition compared with the System 22 jet nebulizers in mechanically
      ventilated patients. Their efficiency, speed of drug delivery, and compatibility
      with mechanical ventilator circuits make ultrasonic nebulizers potentially
      attractive for use during mechanical ventilation.

PMID- 9150334
TI  - Effects of four different methods of sampling arterial blood and storage time on
      gas tensions and shunt calculation in the 100% oxygen test.
AB  - At the present time, plastic syringes are most commonly used for collecting
      arterial blood. The oxygen tension of the arterial blood (Pa,O2) in these
      syringes may fall. We studied the effect of the type of syringe, metabolism, and
      storage time on the arterial oxygen pressures measured and on the pulmonary shunt
      calculated. In 10 patients, 2-3 h after aortacoronary bypass surgery, a 100%
      oxygen test was performed. Four arterial blood gas samples were withdrawn from
      each patient in random order, two in glass syringes and two in plastic syringes.
      One glass and one plastic syringe were stored at room temperature (RT), and the
      others were stored in ice-water (IW). Each sample was analysed as soon as
      possible, and repeated 15, 30, 60 and 120 min after sampling. The Pa,O2
      measurement in blood in the glass syringe in IW measured as soon as possible
      after sampling was considered the "gold standard". Pulmonary shunt calculations
      were performed using the results of the various blood gas analyses. Compared with
      the "gold standard", all of the other methods showed significant deterioration in
      the Pa,O2 measurement. The effect due to diffusion was 0.05 kPa x min(-1), and
      that due to metabolism 0.11 kPa x min(-1). The Pa,O2 in the glass syringes stored
      in IW remained stable with time. The pulmonary shunt was significantly
      overestimated when the "gold standard" blood gas results were not used (range 0.8
      9.9%). Glass (not plastic) syringes should be used in the 100% oxygen test. The
      syringe should be cooled immediately, even when the sample is analysed as soon as
      possible.

PMID- 9150336
TI  - Impact of sleep in respiratory failure.
AB  - Sleep has a physiological influence on respiration, which can have major adverse
      effects on gas exchange in patients with respiratory insufficiency. These effects
      relate largely to a reduction in various stimulant inputs to the brainstem
      respiratory centre. Conditions that may be associated with sleep-related
      respiratory insufficiency range from pulmonary disorders (such as chronic
      obstructive pulmonary disease (COPD)), to central respiratory insufficiency (such
      as central alveolar hypoventilation), neurological and neuromuscular disorders
      (such as polio and muscular dystrophy), and thoracic cage disorders (such as
      kyphoscoliosis). All these conditions have in common the finding of hypoxaemia
      and hypercapnia, which become more pronounced during sleep. The relative
      hypoventilation, which is common to each condition, is due to varying
      combinations of an inadequate respiratory drive and an increase in the work of
      breathing. Management of respiratory insufficiency during sleep should be
      directed first at optimizing the underlying disorder, then at correcting
      hypoxaemia with controlled low-flow supplemental oxygen. Pharmacological therapy
      may be effective in some instances, but the choice of agent varies with the
      underlying disorder. Assisted ventilation is an important part of the management
      of advanced cases, and the recent development of intermittent positive pressure
      ventilation by nasal mask (NIPPV) has been an important advance in this area. Use
      of NIPPV during the night is associated with beneficial effects during the day,
      particularly improved awake gas exchange and respiratory muscle strength, in
      addition to less dyspnoea and improved quality of life. Electrophrenic pacing of
      the diaphragm is helpful in highly selected cases, particularly patients with
      central respiratory insufficiency and high quadriplegia, but is frequently
      complicated by the development of obstructive sleep apnoea.

PMID- 9150335
TI  - The exogenous surfactant Curosurf enhances phosphatidylcholine content in
      isolated type II cells.
AB  - The exogenous surfactant, Curosurf, contains proteins as well as phospholipids.
      We investigated the possibility that these might affect the reutilization of
      exogenous phospholipid by type II alveolar cells isolated from rat lung. The time
      course of incorporation into lamellar bodies of radioactivity from tritiated
      dipalmitoyl-phosphatidylcholine (DPPC) contained within liposomes was studied.
      Rates of uptake were compared between liposomes prepared from pure phospholipids
      and from Curosurf. The incorporation of labelled choline into newly synthesized
      phosphatidylcholine was also determined in the presence of both preparations. The
      rate of DPPC incorporation over the first 4 h was the same, but, after 6 and 8 h,
      the radioactivity associated with lamellar bodies was about 40% higher from
      Curosurf liposomes. By contrast, both Curosurf and the phospholipid mixture
      enhanced choline incorporation into phosphatidylcholine to the same extent. We
      conclude that Curosurf enhances the surfactant-related phosphatidylcholine
      content of type II cells by two mechanisms, one of which depends on the presence
      of proteins in exogenous surfactant. The difference in incorporation of
      radioactivity from liposome-associated labelled dipalmitoyl-phosphatidylcholine
      cannot be explained just by an increase in reutilization of choline from degraded
      dipalmitoyl-phosphatidylcholine.

PMID- 9150337
TI  - Hyperinflation and respiratory muscle interaction.
AB  - Hyperinflation clearly affects respiratory muscle interaction. It commonly
      increases the rib cage contribution to chest wall motion, whilst it reduces the
      abdominal contribution. This change is thought to result from the fact that
      hyperinflation severely reduces the mechanical advantage of the diaphragm, whilst
      it affects the mechanical advantage of the neck and rib cage muscles to a lesser
      extent. The mechanical disadvantage in the diaphragm induced by hyperinflation is
      presumably primarily the result of the length changes undergone by the diaphragm
      in acute hyperinflation. Changes in diaphragmatic geometry are generally
      considered to be less important in the reduction of the diaphragm's force
      generating capacity. Further factors contributing to the mechanical disadvantage
      in the diaphragm include a reduction in the appositional component of
      diaphragmatic action (through reduction in the zone of apposition), and a
      reduction in the insertional component (through a shift in the alignment of the
      diaphragmatic fibres from axial to radial). In chronic hyperinflation, the
      diaphragm adapts to the chronically hyperinflated state. This adaptation to
      chronic foreshortening is similar to the adaptation occurring in the skeletal
      muscle. It is caused by a dropout of sarcomeres in series along the muscle
      fibres. It restores the force-generating capacity of the muscle, in part, but it
      reduces the capacity of the muscle to undergo length changes. The mechanical
      advantage of the parasternal intercostals and the scalenes is possibly less
      affected, because the length changes undergone by these muscles during
      hyperinflation are smaller. The factors determining the mechanical advantage of
      the parasternal intercostals are complex. Variables related to the mechanical
      advantage of the parasternal intercostals include: length changes; changes in
      angle between the parasternal intercostals and the sternum and between rib and
      sternum; and changes in mechanical arrangement among different parasternals. At
      present, it is difficult to develop an integrated view of these factors and of
      their change with hyperinflation. Finally, hyperinflation commonly results in
      recruitment of expiratory muscles. The functional significance of this expiratory
      muscle recruitment in patients is still debated.

PMID- 9150338
TI  - Pleural tuberculosis.
AB  - Tuberculous pleural effusions occur in up to 30% of patients with tuberculosis.
      It appears that the percentage of patients with pleural effusion is comparable in
      human immunodeficiency virus (HIV)-positive and HIV-negative individuals,
      although there is some evidence that HIV-positive patients with CD4+ counts <200
      cells x mL(-1) are less likely to have a tuberculous pleural effusion. There has
      recently been a considerable amount of research dealing with the immunology of
      tuberculous pleurisy. At present, we have more evidence that activated cells
      produce cytokines in a complex pleural response to mycobacteria. Intramacrophage
      elimination of mycobacterial antigens, granuloma formation, direct neutralization
      of mycobacteria and fibrosis are the main facets of this reaction. With respect
      to diagnosis, adenosine deaminase and interferon gamma in pleural fluid have
      proved to be useful tests. Detection of mycobacterial deoxyribonucleic acid (DNA)
      by the polymerase chain reaction is an interesting test, but its usefulness in
      the diagnosis of tuberculous pleurisy needs further confirmation. The recommended
      treatment for tuberculous pleurisy is a 6 month regimen of isoniazid and
      rifampicin, with the addition of pyrazinamide in the first 2 months. HIV patients
      may require a longer treatment. The general use of corticosteroids is not
      recommended at this time, but they can be used in individuals who are markedly
      symptomatic.

PMID- 9150339
TI  - Allergic alveolitis following exposure to epoxy polyester powder paint containing
      low amounts (<1%) of acid anhydrides.
AB  - Only one case report concerning allergic alveolitis caused by polyester powder
      paint has been published previously. The aim of this study was to determine
      whether phthalic anhydride (PA) or trimellitic anhydride (TMA) is the alveolitis
      causing agent in such paint. A 61 year old woman showed recurrent symptoms of
      chills, cough, and fever whilst at work. She was working in a plant where epoxy
      polyester powder paints were used to paint metal. The paint was found to contain
      low (<1%) amounts of TMA and PA. The patient showed shadowing on chest
      radiographs. In bronchoalveolar lavage, lymphocytosis (67%) and a low T-helper/T
      suppressor ratio (0.2) were found. Transfer factor was within normal limits, but
      a slight reduction was verified after re-exposure to the paint. The symptoms,
      exposure, reduction in transfer factor, findings on chest radiographs and
      bronchoalveolar lavage were consistent with allergic alveolitis. In conclusion,
      the polyester powder paint used in the plant caused allergic alve olitis in this
      patient. Of the constituents in the paint, trimellitic anhydride and phthalic
      anhydride were the possible causative agents.

PMID- 9150340
TI  - Atypical mycobacteriosis in a lung transplant recipient.
AB  - Although mycobacterial infections are more frequent in lung transplant recipients
      than in other solid organ recipients only occasional reports of infection from
      atypical Mycobacteria have been reported in patients receiving lung
      transplantation. We present a case of pleural and cutaneous infection due to
      Mycobacterium fortuitum in a double-lung transplant recipient. The infection was
      rapidly responsive to therapy with a two drug regimen and no reduction of
      immunosuppression was necessary.

PMID- 9150341
TI  - Intravascular lymphomatosis diagnosed by transbronchial lung biopsy.
AB  - Intravascular lymphomatosis is a rare lymphoma presenting a variety of symptoms
      due to proliferation of tumour cells within blood vessels in the brain, the skin
      and other organs. This disease is generally considered to be highly malignant,
      but to be relatively susceptible to combined chemotherapy, when diagnosed in the
      early stage. We describe a case of intravascular lymphomatosis, presenting with
      diffuse interstitial shadows on chest radiographic image, which could be
      diagnosed by transbronchial lung biopsy. The patient showed a good response to
      combined chemotherapy. We propose that transbronchial lung biopsy is a useful
      procedure for the diagnosis of intravascular lymphomatosis.

PMID- 9150343
TI  - A comprehensive graphic approach to peak flow "traffic light system" 
      interpretation.

PMID- 9150342
TI  - Diffuse pulmonary calcinosis without calcium metabolism abnormalities in a renal
      transplant recipient.
AB  - Eighteen years after an uneventful renal transplantation, the chest radiograph of
      an asymptomatic 50 year old man showed diffuse bilateral infiltrations,
      predominately at the right apex. Computed tomography (CT) scan demonstrated a
      diffuse alveolar pattern, the alveoli being filled with a very dense material,
      with some tracheal calcifications. Bronchoalveolar lavage fluid analysis was
      normal, but bronchial and transbronchial biopsies revealed calcium deposits in
      the bronchial mucosa and in the alveolar septa. The diagnosis of diffuse
      pulmonary calcinosis was established, despite normal blood calcium, phosphorus
      and magnesium levels, based upon computed tomography scan and pathological
      findings at fibreoptic bronchoscopy, without the need for an open lung biopsy.

PMID- 9150344
TI  - Molecular epidemiology of hematological neoplasms--present status and future
      directions.
AB  - The field of molecular epidemiology, using modern epidemiological approaches and
      taking the advantage of the advances in molecular biology can provide new tools
      for the exploration of etiological determinants, either environmental or
      hereditary, in the development of hematological neoplasms. It is now possible to
      identify some host susceptibility characteristics, to measure the effective dose
      of exposure, and to identify early, pre-clinical biological effects, using
      sensitive and specific biomarkers. The significant variation in the incidence of
      hematological neoplasms in different geographical areas, races, and age groups,
      the high rates of familial aggregation in certain populations, the involvement of
      protooncogenes and tumor suppressor genes in the development of hematological
      neoplasms, as well as of many environmental agents such as chemicals, radiation,
      and viruses, support the important role of molecular epidemiology in the
      investigation of the development of hematological neoplasms.

PMID- 9150345
TI  - The in vitro effects of all-trans-retinoic acid and hematopoietic growth factors
      on the clonal growth and self-renewal of blast stem cells in acute promyelocytic
      leukemia.
AB  - All-trans-retinoic acid (ATRA) has been used as a potent therapeutic agent to
      induce differentiation of acute promyelocytic leukemia (APL) cells, and
      granulocyte colony-stimulating factor (G-CSF) has been reported to enhance this
      effect of ATRA in vitro. We investigated the effects of ATRA and three myeloid
      growth factors, including G-CSF, on the growth of the leukemic stem cells of 10
      APL patients. G-CSF was the most powerful stimulator of leukemic colony formation
      in five out of 10 patients, but was neither the major stimulant of self-renewal
      of the blast stem cells nor an inducer of maturation. In contrast, ATRA was
      highly effective in inducing morphological maturation of leukemic promyelocytes,
      but variable results were obtained in regard to its effects on the growth of
      blast stem cells: ATRA suppressed both clonal growth and self-renewal in some
      patients, but was inactive or even had stimulating effects in the other patients.
      Similar variable effects were observed with the combination of ATRA and G-CSF.
      These findings indicate that the differentiation-inducing effect of ATRA is not
      always associated with growth inhibition of leukemic stem cells in vitro and
      justify the use of chemotherapy in conjunction with ATRA in the treatment of APL.

PMID- 9150346
TI  - Acute promyelocytic leukemia--from the bench to the bedside.

PMID- 9150347
TI  - Cytokines, molecular biological abnormalities, and acute myelogenous leukemia.
AB  - Leukemia cell proliferation is dependent upon cytokines produced by the leukemia
      cells or by the microenvironment under stimulation by leukemia cells. Abnormal
      expression of the p53, rb, and ras genes is associated with cytokine production,
      suggesting that abnormal expression can affect leukemia cells by affecting
      intracellular growth controls and by stimulating cytokine production. While these
      observations suggest that cytokines can be used to stimulate leukemia
      proliferation during cytotoxic therapy increasing the sensitivity to treatment,
      they also suggest that inhibition of cytokine affects could increase clinical
      responses by reducing leukemia cell regrowth between courses of therapy.

PMID- 9150348
TI  - Expression of the MDR1 and MDR3 gene products in acute and chronic leukemias.
AB  - We performed immunocytochemistry to detect mdr1 and mdr3 P-glycoproteins (P-gps)
      in 81 patients with acute and chronic leukemia, using the mdr1 P-gp-specific
      monoclonal antibody (MoAb) MRK16, and the mdr3 P-gp-specific MDR3M.
      Immunoreactivity for the mdr1 gene product was positive in 27 out of 81 (33%)
      patients. Immunoreactivity with the anti-mdr3 P-gp MoAb was positive in 20 out of
      81 (25%) patients. Of 54 patients with acute leukemia, 17 (31%) were positive for
      mdr1 P-gp and 8 (15%) for mdr3 P-gp. A high proportion (60%) of patients with
      chronic lymphocytic leukemia (CLL) were mdr3 P-gp positive. Of the patients with
      granular-lymphocyte proliferative disorder (GLPD), a chronic T-cell or natural
      killer cell leukemia, 8/17 (47%) were positive for mdr1 P-gp and 6/17 (35%) for
      mdr3 P-gp. Of 23 patients with chronic leukemia (CLL and GLPD), 10 (37%) were
      positive for mdr1 P-gp and 12 (44%) for mdr3 P-gp. To clarify the function of the
      mdr3 P-gp, we examined the intracellular rhodamine123 (Rh123) levels of mdr1 P-gp
      negative and mdr3 P-gp-positive leukemic cells from patients with acute
      lymphocytic leukaemia, on the addition of 10 microM cyclosporin A (CyA). The
      addition of CyA led to significant increases in intracellular Rh123 levels in
      mdr1 P-gp-negative and mdr3 P-gp-positive leukemic cells. Results of the assay
      for dye efflux suggested that the mdr3 P-gp has a role in drug resistance, and
      functional drug-efflux capacity. In 31 acute leukemia patients at initial
      diagnosis, mdr1 or mdr3 P-gp expression correlated significantly to an outcome of
      complete remission (CR). In 54 acute leukemia patients, exposure to precytotoxic
      agents correlated significantly to expression, with a significant higher number
      of patients mdr1 or mdr3 P-gp positive than negative. In the 54 patients with
      acute leukemia, mdr1 P-gp expression correlated to mdr3 P-gp expression
      significantly (p=0.0007). In the 27 patients with chronic leukemia (CLL and
      GLPD), mdr1 and mdr3 P-gp expression did not correlate to exposure to
      precytotoxic agents, nor did mdr1 P-gp expression correlate to mdr3 P-gp
      expression. It may be speculated that precytotoxic agents induced mdr1 and mdr3 P
      gp expression in acute leukemia; however, in chronic leukemia, both P-gps were
      expressed independently of exposure to precytotoxic agents.

PMID- 9150349
TI  - CB1093, a novel vitamin D analog; effects on differentiation and clonal growth on
      HL-60 and de novo leukemia cells.
AB  - We studied the effects of a novel vitamin D analog CB1093, EB1089 (one of the
      most antileukemic analogs yet) and 1 alpha,25(OH)2D3 both on HL-60 cells and
      cells from 13 AML patients. Differentiation was measured both by induction of
      superoxide production and non-specific esterase. Cell proliferation was assessed
      by colony assay and 3H-thymidine incorporation. The effect on serum calcium was
      measured in rats. The CB1093 proved to be the most efficient of the analogs
      tested so far, both in inducing differentiation and in inhibiting proliferation.
      This, combined with its low hypercalcemic effect shown here, makes it a promising
      candidate for preclinical animal studies.

PMID- 9150350
TI  - A model system in haematology and immunology: the human monocytic cell line MONO
      MAC-1.
AB  - MONO-MAC-1 is a human cell line with properties of blood monocytes, which can be
      used as a model system to study monocytic functions in vitro. In the present
      study, we prepared a karyotype of MONO-MAC-1, analysed the growth behaviour,
      determined the presence of differentiation-associated antigens and studied the
      expression and secretion of several cytokines upon stimulation with 12-O
      tetradecanoyl phorbol 13-acetate (TPA) and lipopolysaccharide (LPS). The MONO-MAC
      1 cells have a near diploid karyotype and contain several recurrent chromosomal
      rearrangements, in particular the translocation (9;11) commonly found in AML-M5.
      Stimulation with TPA or LPS induced changes in morphology and gene expression,
      especially an increase in the level of the differentiation marker CD14 and the
      production of monocyte-related cytokines. Both biomodulators alone were
      sufficient to promote TNF alpha release; however, the combination of TPA and LPS
      resulted in a synergistic increase of TNF alpha secretion. Northern blot analysis
      indicated that upregulated production of TNF alpha was due to induced synthesis
      of mRNA. The mRNA accumulation peaked approximately 2 h after stimulation and
      maximum levels of TNF alpha were found in the supernatants after 4-8 h of
      culture. The MONO-MAC-1 cells could not be restimulated with the same inducer to
      release TNF alpha when a 48 h pre-treatment was carried out with LPS or TPA. LPS
      induced the release of granulocyte colony-stimulating factor (G-CSF), while TPA
      failed to do so. Vice versa, secretion of macrophage CSF (M-CSF) could be induced
      by TPA, but not by LPS. However, LPS enhanced the TPA-induced M-CSF production.
      Similarly, incubation of MONO-MAC-1, simultaneously with TPA and LPS, led to
      granulocyte macrophage CSF (GM-CSF) and interleukin-1beta (IL-1beta)secretion,
      while both stimulators alone had almost no (TPA) or only a weak (LPS) effect on
      the secretion of GM-CSF and IL-1beta. Our results demonstrate that MONO-MAC-1 is
      a unique cell line with distinct monocytic features; certain monocytic properties
      can be upregulated by activation of intracellular signalling pathway(s). We
      suggest that, besides the LPS receptor CD14, activation of PKC participates in
      these process, especially in the production and secretion of cytokines by MONO
      MAC-1 cells.

PMID- 9150351
TI  - Expression of LECAM-1 and LFA-1 on pre-B lymphoma cells but not on preneoplastic
      pre-B cells in SL/KH mice.
AB  - The pre-B lymphoma-prone inbred strain SL/Kh mice showed a polyclonal expansion
      of BP-1+ pre-B cells in bone marrow early in life. Preneoplastic pre-B cells did
      not express adhesion molecules LECAM-1 and LFA-1, whereas neoplastic pre-B cells
      consistently expressed both molecules. There were two types of pre-B lymphomas in
      SL/Kh with distinct in vivo behavior. One infiltrated lymph nodes and spleen and
      another, predominantly bone marrow. However, lymphoma cells of both types
      expressed BP-1, LECAM-1 and LFA-1. Expression of these adhesion molecules on BP
      1+ cells, therefore, may represent an important consequence of pre-B
      lymphomagenesis in SL/Kh strain, but is not sufficient to explain the in vivo
      behavior of the pre-B lymphoma cells.

PMID- 9150352
TI  - The human bladder carcinoma cell line 5637 constitutively secretes functional
      cytokines.
AB  - We have studied cytokine secretion by the human bladder carcinoma cell line 5637
      using growth factor-dependent cell line bioassays and specific ELISA. The 5637
      cell line-conditioned medium (5637 CM) stimulated proliferation of human growth
      factor-dependent leukemia cell lines in a dose-dependent fashion. Quantitation by
      specific ELISA and by bioassays detected high amounts of G-CSF and GM-CSF and
      smaller quantities of IL-1beta, M-CSF and SCF in 5637 CM; the concentration of IL
      3 was below the detection level of the ELISA, if present at all. The G-CSF and GM
      CSF activities secreted by 5637 cells could be inhibited specifically by
      neutralizing anti-G-CSF and anti-GM-CSF antibodies. In conclusion, 5637 bladder
      carcinoma cells constitutively produce and secrete several functionally active
      cytokines; 5637 CM is a valuable, reliable and inexpensive source for cytokines,
      for instance for the culture of growth factor-responsive or -dependent
      hematopoietic primary cells and cell lines.

PMID- 9150353
TI  - Acute myeloid leukemia M2B (subacute myeloid leukemia) in China.

PMID- 9150354
TI  - A patient with myeloma who still has pure red cell aplasia despite the most
      intensive immune modulation.

PMID- 9150355
TI  - The mouse mammary tumor associated gene INT3 is a unique member of the NOTCH gene
      family (NOTCH4).
AB  - The INT3 gene is frequently rearranged in mouse mammary tumor virus (MMTV)
      induced mammary tumors of the CzechII mouse strain. We have completed the
      nucleotide sequence of the normal 6.5 Kb INT3 RNA and defined the intron/exon
      boundaries of the gene. The open reading frame of INT3 RNA should encode a 200 kd
      protein which shares 60% homology with the mouse homologue of Drosophila NOTCH.
      INT3 is unique among other members of the NOTCH family by containing 29 instead
      of 36 EGF-like repeats in the extracellular domain of the gene product. Five
      novel EGF-like repeats have been created as consequence of apparent small
      deletions which have occurred within the coding region for the extracellular
      domain during evolution. Nucleotide sequence analysis of host-viral junction
      fragments from nine independent MMTV-induced mammary tumors containing a
      rearranged INT3 gene reveals that all of the integration events occur within a
      174 bp region 3' of the sequences encoding the LIN12 repeats in the INT3
      extracellular domain and 5' of the sequences encoding the transmembrane domain.
      Therefore, the only tumorigenic INT3 mutations resulting from MMTV proviral
      insertions are those which results in the expression of the intracellular domain.
      This strongly suggests that MMTV-induced activation of INT3 is manifest in the
      absence of the regulatory action of the extracellular domain, including the LIN12
      repeat sequences, leaving the expressed intracellular domain constitutively free
      to function in its role in mammary tumorigenesis.

PMID- 9150356
TI  - DPC4 (SMAD4) mediates transforming growth factor-beta1 (TGF-beta1) induced growth
      inhibition and transcriptional response in breast tumour cells.
AB  - A family of structurally related proteins homologous to the Drosophila mothers
      against dpp (MAD) gene product have been implicated in signal transduction by
      members of the TGF-beta superfamily. One of these MAD related proteins (DPC4) has
      been cloned as a candidate tumour suppressor in pancreas carcinomas, suggesting a
      role for DPC4 in growth regulation by TGF-beta related proteins. The involvement
      of DPC4 in TGF-beta1 induced growth inhibition and transcriptional response is
      demonstrated here, by the introduction of DPC4 in the TGF-beta and activin
      insensitive breast tumour cell line MDA-MB-468, from which the DPC4 gene is
      deleted. Transfection of DPC4 in this cell line restores both growth inhibition
      and the induction of a TGF-beta sensitive reporter construct (3TPlux) by TGF
      beta1. In contrast, a DPC4 splice variant lacking amino acid residues 223-301 and
      cloned from another TGF-beta and activin resistant breast tumour cell line (MDA
      MB-231), does not restore the induction of the 3TPlux reporter by TGF-beta1. We
      also show that in this latter cell line activin resistance is partly due to the
      absence of a functional activin type IB receptor. These results indicate that
      DPC4 is part of the TGF-beta signalling cascade and mediates TGF-beta induced
      growth inhibition. Together with the deletion of DPC4 from pancreas carcinomas
      these results suggest a role for DPC4 as a tumour suppressor.

PMID- 9150357
TI  - Human small Maf proteins form heterodimers with CNC family transcription factors
      and recognize the NF-E2 motif.
AB  - The transcription factor NF-E2, a heterodimeric protein complex composed of p45
      and small Maf family proteins, is considered crucial for the regulation of
      erythroid gene expression and platelet formation. To facilitate the
      characterization of NF-E2 functions in human cells, we isolated cDNAs encoding
      two members of the small Maf family, MafK and MafG. The human mafK and mafG genes
      encode proteins of 156 and 162 amino acid residues, respectively, whose deduced
      amino acid sequences show approximately 95% identity to their respective chicken
      counterparts. Expression of mafK mRNA is high in heart, skeletal muscle and
      placenta, whereas mafG mRNA is abundant in skeletal muscle and is moderately
      expressed in heart and brain. Both are expressed in all hematopoietic cell lines,
      including those of erythroid and megakaryocytic lineages. In electrophoretic gel
      mobility shift assays binding to NF-E2 sites was found to depend on formation of
      homodimers or heterodimers with p45 and p45-related CNC family proteins. The
      results suggest that the small Maf family proteins function in human cells
      through interaction with various basic-leucine zipper-type transcription factors.

PMID- 9150358
TI  - Cellular localisation of the ataxia-telangiectasia (ATM) gene product and
      discrimination between mutated and normal forms.
AB  - The recently cloned gene (ATM) mutated in the human genetic disorder ataxia
      telangiectasia (A-T) is involved in DNA damage response at different cell cycle
      checkpoints and also appears to have a wider role in signal transduction.
      Antibodies prepared against peptides from the predicted protein sequence detected
      a approximately 350 kDa protein corresponding to the open reading frame, which
      was absent in 13/23 A-T homozygotes. Subcellular fractionation,
      immunoelectronmicroscopy and immunofluorescence showed that the ATM protein is
      present in the nucleus and cytoplasmic vesicles. This distribution did not change
      after irradiation. We also provide evidence that ATM protein binds to p53 and
      this association is defective in A-T cells compatible with the defective p53
      response in these cells. These results provide further support for a role for the
      ATM protein as a sensor of DNA damage and in a more general role in cell
      signalling, compatible with the broader phenotype of the syndrome.

PMID- 9150359
TI  - Polyomavirus large T antigen overcomes p53 dependent growth arrest.
AB  - Polyomavirus transforms cells in culture and induces tumors in mice without
      apparent interaction with or inactivation of the p53 tumor suppressor protein. In
      this report we investigate the ability of polyomavirus T antigens to overcome the
      growth suppression function of p53. A temperature sensitive p53 gene was
      introduced into mouse embryo fibroblasts derived from a p53 null mouse, resulting
      in expression of a protein with a mutant conformation at 37 degrees C and a
      functionally wild-type conformation at 32 degrees C. We found that expression of
      p53 at 32 degrees C induced the cyclin-dependent kinase inhibitor p21/WAF1 and
      arrested cell growth in the G1/G0 phase of the cell cycle. Only the under
      phosphorylated form of the retinoblastoma tumor suppressor protein (pRB) was
      detected in these growth arrested cells. We introduced both polyomavirus large T
      (LT) and middle T (MT) antigens into this cell line and showed that LT overcame
      p53-dependent growth arrest, while MT did not. In cells grown at 32 degrees C, LT
      expession led to cell proliferation and phosphorylation of pRB in the presence of
      p21. A mutant LT containing a defective pRB binding domain failed to overcome the
      growth arrest, indicating that interaction of LT with RB proteins is required to
      override p53 function. Although the polyomavirus T antigens do not interact with
      p53 directly, our results indicate that the virus, through LT, is able to
      interfere with the growth suppressive activity of p53.

PMID- 9150360
TI  - Actin cytoskeleton polymerization in Dbl-transformed NIH3T3 fibroblasts is
      dependent on cell adhesion to specific extracellular matrix proteins.
AB  - The Dbl oncogene is the putative exchange factor for two small GTP-binding
      proteins, RhoA and CDC42 which are involved in the polymerization of actin to
      produce stress fibers and filopodia, respectively. We report here that Dbl
      oncogene-transformed NIH3T3 cells show actin stress fibers only when cells are
      plated on fibronectin. Plating of cells on collagen I and IV as well as on poly-D
      lysine and gelatin induces polymerization of actin to form filopodia,
      lamellipodia and membrane ruffles but not stress fibers. The putative collagen
      receptors, alpha1/beta1 and alpha2/beta1 integrins are expressed at reduced level
      in Dbl-transformed cells compared to untransformed NIH3T3 fibroblasts.
      Nevertheless, adhesion to collagens is not altered. Inhibitory monoclonal
      antibody to mouse integrin beta1 subunit blocked adhesion of both Dbl-transformed
      and untransformed NIH3T3 cells, demonstrating that adhesion to collagen I and IV
      is mediated by the beta1 family of integrins. Dbl product rapidly induces the
      depolymerization of actin stress fibers, rounding up of the cells, and formation
      of filopodia and lamellipodia when microinjected in NIH3T3 cells plated on
      gelatin. Thus, Dbl may exert its effect on actin cytoskeleton organization in
      response to extracellular proteins by altering integrin-mediated signalling
      pathways.

PMID- 9150361
TI  - Signal transduction through atypical PKCs, but not the EGF receptor, is necessary
      for UVC-induced AP-1 activation in immortal murine cells.
AB  - The exposure of mammalian cells to ultraviolet (u.v.) irradiation leads to
      activation of transcription factors, such as AP-1 and NFkappaB. It is postulated
      that the EGF receptor but not protein kinase C (PKC) is the major membrane
      mediator in UVC-induced signal transduction. We demonstrate here that the
      antisense oligonucleotides of PKC zeta and the dominant negative mutant of PKC
      lambda/iota as well as dominant negative PKC zeta markedly blocked UVC-induced AP
      1 activity. In contrast, UVC-induced AP-1 activity in cells devoid of the EGF
      receptor (B82), is not significantly different from that of the stable
      transfectants with a kinase-deficient EGF receptor (B82M721), or wild-type EGF
      receptor (B82L). This was found at all UVC irradiation doses and time courses
      studied, while high levels of EGF-induced AP-1 activity were observed in B82L
      cells but not in B82 cells. This evidence strongly suggests that atypical PKCs,
      but not the EGF receptor, is necessary for UVC-induced AP-1 activation in JB6 and
      B82 cells.

PMID- 9150362
TI  - Evidence for the inactivation of multiple replicative lifespan genes in immortal
      human squamous cell carcinoma keratinocytes.
AB  - Human keratinocyte immortality is genetically recessive to the normal phenotype
      of limited replicative lifespan and appears to require the dysfunction of p53 and
      the cyclin D-Cdk inhibitor p16. In order to test for the inactivation of other
      candidate replicative lifespan genes in the immortal cells of human tumors, we
      developed a series of mortal and immortal keratinocyte cultures derived from
      neoplastic lesions of the head and neck which were amenable to molecular genetic
      analysis by the loss of heterozygosity (LOH) technique. The results indicate that
      keratinocyte immortalization in head and neck squamous cell carcinoma (SCC-HN)
      development involves the inactivation of at least two further pathways to
      senescence and four in all. Chromosomes 1, 4 and 7 carry genes representing
      immortality complementation groups C, B and D respectively and immortal
      keratinocytes showed LOH at either 4q32-q34 between D4S1554 and D4S171 (group B)
      or 7q31 (group D) but never 1q25 (group C). These results tentatively suggest
      that the genes responsible for the immortality complementation groups encode
      proteins on the same pathway to senescence. In addition, all of the immortal
      keratinocyte lines possessed high levels of telomerase activity and a suppressor
      of telomerase activity has been mapped to the short arm of chromosome 3p. Five
      out of eight lines showed LOH at 3p21.2-p21.3, a region which may carry a gene
      capable of suppressing SCC-HN telomerase. However, alternative mechanisms of
      telomerase reactivation were also suggested by our results. None of the above
      genetic alterations were seen in seven senescent neoplastic keratinocyte
      cultures. Other loci harbouring antiproliferative genes implicated in replicative
      lifespan showed few or no alterations and any alterations seen were additional to
      those described above.

PMID- 9150363
TI  - Mapping of adenovirus 5 E1A domains responsible for suppression of neu-mediated
      transformation via transcriptional repression of neu.
AB  - Overexpression of neu (also known as c-erbB-2 or HER-2) commonly occurs in human
      cancer and is also known to enchance tumor metastasis and chemoresistance. Our
      earlier reports showed that the adenovirus 5 E1A can suppresss the neu-mediated
      transformation by repression of neu. Thus, E1A has the potential to be used as a
      therapeutic agent against the neu-overexpressing human cancers. However, a
      serious concern to this approach is that E1A is also capable of immortalizing
      primary culture cells and can co-operate with ras or E1B oncogenes to transform
      them. The E1A CR2 domain (amino acid residues 120 to 140) necessary for binding
      to RB is believed to be required for this oncogenic function. Here, we report
      that deletion of CR2 region did not affect E1A's capability to repress neu.
      Interestingly, deletion of the amino acid residues 4 to 25 or 40 to 80 completely
      disrupted E1A-mediated neu repression. By deleting the amino acid residues from
      81 to 185, we have successfully generated a mini-E1A mutant that was sufficient
      to inhibit neu promoter activity and suppress neu-mediated transformation. The
      mini-E1A mutant does not contain the CR2 domain that is crucial for RB binding
      and immortalization, and hence, may serve as a more selective tumor suppressor,
      and a safer therapeutic agent. It may also be a useful tool to further
      investigate the molecular mechanism(s) of neu overexpression and E1A-mediated
      transcriptional repression in cancer cells.

PMID- 9150364
TI  - Identification of a zinc-finger gene at 6q25: a chromosomal region implicated in
      development of many solid tumors.
AB  - We have used a rat model of epithelial ovarian cancer to identify a gene that
      shows decreased or lost expression in independently transformed rat ovarian
      surface epithelial cell lines compared to the normal progenitor cells. Hence, we
      refer to this gene as Lot-1 (Lost on transformation 1, GenBank accession no.
      U72620). Here, we report the cloning of the likely human homologue and its
      initial characterization. The deduced amino acid sequences of the cDNAs for rat
      and human LOT-1 (GenBank accession no. U72621) contain seven zinc finger motifs
      of the C2H2 type as well as proline and glutamine rich areas. The genes share
      76.4% identity at the nucleotide level, 67.7% at the amino acid level and 85.5%
      within the seven zinc finger motifs. LOT-1 is ubiquitously expressed in normal
      human tissues but was not expressed in four of 11 (36%) human ovarian cancer cell
      lines or spontaneously transformed human ovarian surface epithelial cells. The
      human gene maps to chromosome 6 at band q25. We show that there is a 38%
      incidence of allelic loss at this chromosomal location in human ovarian cancers.
      This chromosomal region has also been implicated in the genesis of breast,
      kidney, and pleural mesothelial cancers. We suggest that this newly identified
      gene is not only of intrinsic interest as a ubiquitously expressed probable
      transcription factor but is a plausible candidate for the tumor suppressor gene
      which likely resides in the region of chromosome 6 defined by band q25.

PMID- 9150366
TI  - A region of interstitial 17q25 allelic loss in ovarian tumors coincides with a
      defined region of loss in breast tumors.
AB  - Chromosomal regions of allelic imbalance in tumors are predicted to define the
      general location of tumor suppressor genes. We previously localized a putative
      breast tumor suppressor gene to a 3 cM region on 17q25 by deletion mapping of
      microsatellite markers in breast tumors. To determine if the same 17q25 region of
      loss is important in the genesis of other tumor types, 32 ovarian tumors and 24
      prostate tumors, as well as 33 additional breast tumors, were analysed with 17q25
      polymorphic microsatellite markers. While no significant loss was observed in
      prostate tumors, greater than half of ovarian tumors exhibited loss coincident
      with the candidate region previously defined in breast tumors. These results
      suggest that one or more novel tumor suppressor genes exist on 17q25 within a
      concordant region of interstitial loss defined in both breast and ovarian
      neoplasms.

PMID- 9150365
TI  - Cyclin D1 expression is a major target of the cAMP-induced inhibition of cell
      cycle entry in fibroblasts.
AB  - We previously described in the CCL39 hamster fibroblast cell line the inhibition
      of DNA synthesis reinitiation by agents that elevate cyclic AMP. Here, we show
      that 8Br-cAMP strongly blocks both the growth factor-induced increase in cyclin
      D1 protein expression and decrease in p27(KIP1) protein levels, leaving untouched
      the levels of cyclin D3, cdk2 and cdk4. To assess the role of cyclin D1 in the
      cAMP-mediated inhibition of DNA synthesis, we overexpressed the cyclin D1 gene in
      CCL39 and analysed the cAMP response in stable transfectants. We showed that the
      kinase activities associated to G1 cyclin-cdk complexes are significantly more
      resistant to cAMP in cyclin D1 transfectants than in their normal counterparts,
      although the serum-induced p27(KIP1) disparition is still cAMP sensitive in
      cyclin D1 overexpressors. Interestingly, the mitogen-induced DNA synthesis
      reinitiation is also much less inhibited by cAMP in cyclin D1 transfectants than
      in control cells. These data clearly establish that the cAMP-inducible blockade
      of the G1 phase of the cell cycle can be partially alleviated by overexpression
      of cyclin D1 in hamster fibroblasts, thus strongly suggesting that cyclin D1
      protein is one of the major targets for cAMP inhibitory action in fibroblasts.

PMID- 9150367
TI  - Transcriptional activation of the matrix metalloproteinase-9 gene in an H-ras and
      v-myc transformed rat embryo cell line.
AB  - The 92 kd type IV collagenase/gelatinase (MMP-9) is important in mediating
      basement membrane and extracellular matrix degradation in metastasis. Because MMP
      9 is made in tumor cells, but not in quiescent normal cells, we wished to
      identify the transcriptional elements responsible for its synthesis in tumor
      cells. We chose to characterize transcriptional regulation of the MMP-9 gene in a
      highly metastatic H-ras and v-myc transformed rat embryo cell line which
      overexpresses MMP-9. Using transient transfection of reporter gene constructs
      containing either 5'-deleted or mutated MMP-9 promoter fragments, as well as
      electrophoretic mobility shift assays, we have demonstrated that multiple
      transcription factor consensus binding motifs in the promoter, including those
      for NFkappaB, SP-1, Ets, AP-1, and a retinoblastoma binding element, participate
      in transcriptional regulation of MMP-9 expression in this cell line. Also,
      deletion of an alternating purine-pyrimidine tract in the downstream promoter was
      found to decrease transcriptional activity, suggesting that promoter conformation
      may be important in MMP-9 regulation. Thus multiple pathways leading to
      activation of NFkappaB, SP-1, Ets, AP-1, and retinoblastoma binding factors in
      tumor cells all may contribute to MMP-9 transcription and hence to metastasis.

PMID- 9150368
TI  - Interaction between Cdc37 and Cdk4 in human cells.
AB  - Using the yeast two-hybrid system we have identified novel potential Cdk4
      interacting proteins. Here we described the interaction of Cdk4 with a human
      homologue of the yeast Drosophila CDC37 gene products. Cdc37 protein specifically
      interacts with Cdk4 and Cdk6, but not with Cdc2, Cdk2, Cdk3, Cdk5 and any of a
      number of cyclins tested. Cdc37 is not an inhibitor nor an activator of the
      Cdk4/cyclin D1 kinase, while it appears to facilitate complex assembly between
      Cdk4, and cyclin D1 in vitro. Cdc37 competes with p16 for binding to Cdk4,
      suggesting that p16 might exert part of its inhibitory function by affecting the
      formation of Cdk4/cyclin D1 complexes via Cdc37.

PMID- 9150369
TI  - Differential effects of acetylcholine and bradykinin on prostanoid release from
      the rat mesenteric bed: role of endothelium and of nitric oxide.
AB  - The roles of nitric oxide and of endothelium in the effects of the vasorelaxing
      agents acetylcholine and bradykinin on the production of prostanoids was studied
      in the isolated and perfused mesenteric vascular bed of the rat. Prostanoids were
      measured in the perfusate by high-performance liquid chromatography (HPLC). In
      the intact vascular bed, 1 microM bradykinin increased the release of 6-keto
      prostaglandinF(1alpha) (stable metabolite of prostacyclin) and of prostaglandin
      E2 and 10 microM acetylcholine stimulated the efflux of prostacyclin only. In the
      de-endothelialized vascular bed, bradykinin increased the release of prostacyclin
      whereas acetylcholine increased the efflux of thromboxane. The inhibition of
      nitric oxide synthesis with 100 microM N(G)-nitro-L-arginine methyl ester
      prevented the effect of bradykinin but did not modify the effects of
      acetylcholine on prostanoid release. In addition, 100 microM L-arginine reversed
      the inhibitory effect of N(G)-nitro L-arginine methyl ester on bradykinin
      stimulated prostaglandin production. It is concluded that acetylcholine and
      bradykinin stimulate prostanoid release in the rat mesenteric vascular bed with
      different patterns and through different mechanisms.

PMID- 9150370
TI  - Effects of the incubation of long-chain polyunsaturated fatty acids on platelet
      lipids and thromboxane release.
AB  - Alterations of dietary lipids have been advocated to manipulate platelet release
      of thromboxane A2. We studied the effects of incubating platelets with several
      different polyunsaturated fatty acids on platelet-lipid profile and release of
      thromboxane A2 in response to platelet stimulation. Porcine platelets were
      isolated by centrifugation, washed three times in Tyrode's solution, and
      incubated with fatty acids (500 microM) in Tyrode's solution with albumin. Seven
      polyunsaturated fatty acids of varying lengths (18-, 20-, and 22-carbon chain) of
      the omega3 and omega6 families were incubated for 60 min at concentrations of 0,
      10, 30, and 100 microM with saturated fatty acids comprising the remainder of the
      500 microM fatty acids. The platelets were then stimulated for 5 min with A23187
      (30 microM). Indomethacin was added, and the platelets were pelleted. Platelet
      lipids were extracted in hexane, transesterified and quantified by gas
      chromatography. Using radioimmunoassay, we measured thromboxane B2, the stable
      metabolite of thromboxane A2, in the platelets' supernatant. A 1-h incubation in
      each of the seven polyunsaturated fatty acids had no significant effect on
      platelet-lipid composition. We found a significant increase in thromboxane B2
      production in arachidonic acid (100 microM) incubated platelets (324.0 +/- 63.8%
      of baseline) that was inhibited by eicosapentaenoic acid (81.0 +/- 26.8%, P <
      0.01) and to a lesser extent by dihomogammalinolenic acid (189.8 +/- 28.3%, P <
      0.03). We conclude that in altering diets to affect platelet release of
      thromboxane, the two fatty acids of interest are the 20-carbon chain fatty acids,
      dihomogammalinolenic acid and eicosapentaenoic acid. The ideal amount of each of
      these fatty acids to be incorporated entails supraphysiologic but
      pharmacologically achievable levels of fatty acids in plasma.

PMID- 9150371
TI  - Role of nitric oxide on uterine and ovarian prostaglandin synthesis during
      luteolysis in the rat.
AB  - In previous studies in our laboratory, we demonstrated that oxytocin (oxy)
      augmented prostaglandin F(2alpha) (PGF(2alpha)) synthesis via enhancing the
      uptake of Ca2+ by uterine tissue. On the other hand, we have shown that oxy
      enhances PGF(2alpha) synthesis in uterine and ovarian tissues during the corpus
      luteum (CL) regression in the rat. In the present study we explore the possible
      relation between endogenous nitric oxide (NO) and oxy on PGs synthesis during the
      luteolytic phase in the rat. The experiments were done in uterine and ovarian
      preparations isolated from pseudopregnant (psp) rats during the luteolytic phase.
      Tissues were incubated "in vitro" with 1)- oxy (50 mU/ml), 2)-NMMA (N(G)
      monomethyl-L-arginine), a potent NOs inhibitor (300 uM), and 3)- both reagents
      (oxy + NMMA). NMMA decreases the synthesis of both PGs (PGE and PGF(2alpha)) and
      oxy enhances PGF(2alpha) synthesis in uterine and ovarian tissue. When reagents
      were used in combination (oxy + NMMA), we found different results in uterus and
      ovaries; i.e., in uterine tissue the NO inhibition did not affect the increase of
      PGF(2alpha) synthesis by oxy. Meanwhile, in ovaries the oxy effect over the
      PGF(2alpha) synthesis was not seen when NOs was inhibited. Probably oxy acts via
      different mechanisms on PGF(2alpha) synthesis in uterine and ovarian tissue. This
      assumption was confirmed when the NOs activity in both tissues (uterine and
      ovarian) was measured after oxy treatment. We found that oxy enhanced the NOs
      activity in ovarian tissues from psp rats but did not modify the enzyme activity
      in uterine tissue.

PMID- 9150372
TI  - Effects of gamma-linolenic acid and arachidonic acid on cell cycle progression
      and apoptosis induction in normal and transformed cells.
AB  - The effects of arachidonic acid (AA) and gamma-linolenic acid (GLA) on cell cycle
      progression and apoptosis induction, using flow cytometry, were compared on
      normal human skin fibroblasts, strain HSF43 with wild type (wt) p53, large T
      antigen transformed HSF43 cells (line E8T4) with non functional p53, and on two
      lymphoblast cell lines, TK6 with wt p53 and WTK1 with mutant p53. AA and GLA
      caused similar dose (50, 75 and 100 microg/ml AA and GLA) and time dependent (24
      and 48 h) induction of apoptosis in each cell line. The degrees of the response
      of the four cell lines were, however, different. The normal HSF43 cells were most
      resistant against apoptosis induction and the WTK1 cells most susceptible. The
      apoptosis induction appeared to be independent of functional p53. Cell cycle
      progression was also similarly affected by AA and GLA in the two cell types. In
      the fibroblast type cells (HSF43 and E8T4) S- and G2/M-phase arrests were evident
      after 48 h exposure to AA and GLA, and in the lymphoblast cell lines (TK6 and
      WTK1) the cells were arrested in the G1-phase.

PMID- 9150373
TI  - Effect of nordihydroguaretic acid and fluconazole on the LTC4/PGE2 ratio in the
      kidney of mice damaged by Candida albicans.
AB  - The kidney is a major target organ in generalized candidiasis. When mice were
      infected with C.albicans, prostaglandin E2 (PGE2)-like activity was found to be
      significantly decreased while leukotriene C4 (LTC4)-like activity increased in
      the kidneys within 10 days. The aim of this study is to investigate the effect of
      nordihydroguaretic (NDGA) and fluconazole on the LTC4/PGE2 ratio in the mice
      kidneys infected by proteinase (+) C. albicans. The LTC4/PGE2 ratio was found to
      be significantly decreased both in NDGA and fluconazole-pretreated groups. These
      results indicate that pretreatment with the lipoxygenase inhibitor NDGA and the
      antifungal drug fluconazole, protect the kidney against C. albicans infection.
      These results also indicate a possible role of arachidonic acid metabolites
      (increase LTC4 and decrease PGE2) in kidney damage due to C. albicans infection.

PMID- 9150374
TI  - Cytotoxic action of alpha-linolenic and eicosapentaenoic acids on myeloma cells
      in vitro.
AB  - Both alpha-linolenic (ALA) and eicosapentaenoic acids (EPA) were toxic to SP 2/0
      mouse myeloma cells in vitro. On the other hand, linoleic acid (LA), gamma
      linolenic acid (GLA), di-homo-gamma linolenic acid (DGLA), arachidonic acid (AA),
      docosahexaenoic acid (DHA) and oleic acid (OA) were much less effective in their
      growth suppressive actions. Both nordihydroguaiaretic acid (NDGA) and
      Indomethacin (IM) could block the action of the fatty acids indicating a role for
      prostaglandins (PGs) and leukotrienes (LTs) in the growth suppressive action of
      ALA and EPA. Superoxide dismutase (SOD) completely blocked, while vitamin E and
      reduced glutathione (GSH) could prevent to a limited extent the anti
      proliferative effects of ALA and EPA. Catalase, mannitol, chlorpromazine (CPZ)
      and trifluoperazine (TFP) did not block the cytotoxic actions of ALA and EPA.
      N(G)-mono-methyl L-arginine (N(G)MMA), an analogue of L-arginine, which inhibits
      nitric oxide synthase, was ineffective in preventing the cytotoxicity induced by
      ALA and EPA. Fatty acid analysis of the various lipid fractions of SP 2/0 cells
      treated with ALA and EPA showed significant incorporation of these fatty acids in
      the cell membrane lipid pools. These results suggest that ALA and EPA induced
      suppression of SP 2/0 cell proliferation is cyclo-oxygenase (CO), lipoxygenase
      (LO) and superoxide dependent. Lipid peroxidation has only a limited role in this
      process. Both calmodulin dependent process and L-arginine derived nitric oxide do
      not seem to have a role in the cytotoxic action of ALA and EPA in these cells.

PMID- 9150375
TI  - Tumor cell-endothelial cell interactions: evidence for roles for lipoxygenase
      products of arachidonic acid in metastasis.
AB  - Adhesion of tumor cells (TC) to endothelial cells (EC) is necessary for movement
      of TC out of the interstitium to form metastatic deposits. This interaction may
      be influenced by proadhesive molecules such as lipoxygenase products of
      arachidonic acid metabolism. We studied the effect of inflammatory stimuli,
      A23187 calcium ionophore, n-formyl-methionyl-leucine-phenylalanine (FMLP) and
      phorbol myristate acetate (PMA) on TC-EC interaction. Adherence of metastatic
      breast tumor cell line (MCF-7), choriocarcinoma cell line (JEG-3), and non
      metastatic pituitary cell (GH-3) were assayed as the number of radiolabeled TC
      attached to EC (cpm/well). TC and EC were incubated with A23187, FMLP, and PMA
      for varying time periods. Lipoxygenase products (LTB4, 5-HETE) were measured
      under basal and stimulated conditions using RP-HPLC and RIA. There were no
      differences in basal adherence of TC lines to EC. When EC were incubated with
      stimuli, there were significant increases in the numbers of MCF-7 and JEG-3 cells
      adherent to EC compared to GH-3. Light and phase contrast microscopy confirmed
      that TC were attached to EC. Upon stimulation, GH-3 preferentially produced
      prostaglandins (PGI1(2)) while MCF-7 and JEG-3 produced lipoxygenase products
      (LTB4 and 5-HETE). Pre-incubation of MCF-7 and JEG-3 with the lipoxygenase
      inhibitor nordihydroguiaretic acid resulted in partial inhibition of adhesion to
      EC. Our data strongly indicate a role for lipoxygenase products of arachidonic
      acid in adherence of TC to EC.

PMID- 9150376
TI  - Antiedematous effects of combination therapies with the leukotriene synthesis
      inhibitor BAY X 1005 in the archidonic acid-induced mouse ear inflammation test.
AB  - The leukotriene synthesis inhibitor (LSI) BAY X 1005 was tested in the
      arachidonic acid (AA)-induced mouse ear inflammation test (AA-MEIT) alone and in
      combination with other representative anti-inflammatory compounds for
      antiedematous effects. When BAY X 1005 was used as a monotherapy, the ED50 (half
      maximal effect) was observed at 5.1 mg/kg per os (p.o.) and at 0.8 microg for
      topical application. The maximal inhibition of edema formation was estimated to
      be 63% for p.o. application and 54% for topical application. Furthermore,
      experiments were carried out in which the animals were conditioned with a
      combination of the H1/5-HT receptor antagonists pyrilamine and methysergide in
      addition to treatment with BAY X 1005. This conditioning treatment alone, without
      BAY X 1005, resulted in a 45 +/- 13% reduction in edema formation. ED50 substance
      effects were observed at 5.3 mg/kg p.o. and at 0.02 microg per ear for topical
      application. The maximal inhibition of edema formation in the conditioned groups
      was 82% for the oral administration of BAY X 1005 and 72% for the topical
      application. To further characterize the antiinflammatory properties of BAY X
      1005 in the conditioned and unconditioned AA-MEIT, BAY X 1005 was tested in
      combination with the nitric oxide (NO) synthase inhibitor L-NAME, with the
      cyclooxygenase inhibitor indomethacin, and in combination with both compounds.
      BAY X 1005 consistently exerted anti-inflammatory effects in the AA-MEIT. The
      effects of a combination of different inhibitors of inflammatory mediators were
      not simply additive in this model, as was demonstrated in the case of the
      combination of L-NAME and indomethacin where a smaller inhibition than with
      either substance alone was observed. In the conditioned model, a combination of
      BAY X 1005 with L-NAME or indomethacin, or with both compounds together was less
      effective than the monotherapy with BAY X 1005. Taken together, these data
      suggest that cyclooxygenase products and NO have little effect on edema formation
      in the conditioned and unconditioned AA-MEIT model and that their interaction
      with leukotrienes is of minor quantitative importance. Our results underline the
      complexity of the AA-MEIT model and provide a rationale for H1/5-HT-conditioning
      animals to compensate for peculiarities in the mouse-specific mediator spectrum
      and to recognize the importance of the leukotriene-specific inflammatory
      response.

PMID- 9150377
TI  - Gamma linolenic acid regulates gap junction communication in endothelial cells
      and their interaction with tumour cells.
AB  - Tumour-endothelial cell adhesion forms a key role in the establishment of distant
      metastases. This study examined the effect of gamma linolenic acid (GLA), an anti
      cancer polyunsaturated fatty acid (PUFA), on both the gap junction communication
      of human vascular endothelial cells and tumour cell-endothelial interactions. By
      using scrape loading of Lucifer yellow dye, we showed that GLA at non-toxic
      levels increased Lucifer yellow transfer, indicating improved gap junction
      communication. The fatty acid also corrected the communication that was reduced
      by the mitogenic and motogenic factor HGF/SF. GLA inhibited the tyrosine
      phosphorylation of connexin-43, a protein that formed gap junction in this cell.
      When human tumour cells were added to quiescent or HGF/SF-activated endothelial
      cells, the presence of GLA reduced adhesion of tumour cells to the endothelium.
      It is concluded that GLA reduces tumour-endothelium adhesion, partly by improved
      gap junction communications of the endothelium.

PMID- 9150378
TI  - Effects of aminoguanidine and N(G)-nitro-L-arginine methyl ester on vascular
      responses of aortae and lungs from streptozotocin-diabetic rats.
AB  - Aminoguanidine (AG) treatment can prevent the development of some functional
      anomalies in experimentally diabetic rats, possibly via the prevention of a
      diabetes-induced vascular dysfunction. The acute effects of AG on endothelium
      dependent relaxation of aortae in the presence of indomethacin and on pressor
      responses and prostacyclin release in isolated perfused lungs, were therefore
      investigated using tissues from control and streptozotocin-diabetic rats.
      Endothelium-dependent relaxations of aortae were reduced by aminoguanidine
      (control 20%, and diabetic 25%). For lungs, angiotensin II-induced pressor
      responses were unaffected by AG, whereas the nitric oxide synthase inhibitor L
      NAME caused integrated pressor responses to be increased in lungs from control
      and diabetic rats (2.0 and 1.8 fold respectively). Individually, AG (1 mM) and L
      NAME (10 microM) did not affect total cumulative prostacyclin release by control
      lungs, whereas significant increases for both were observed for diabetic lungs.
      In summary, these studies firstly provide evidence that AG can increase
      prostacyclin release from tissues in vitro, with little effect upon endothelium
      dependent vasodilatation, and secondly, that the regulation of vasodilator
      prostanoid release by the pulmonary circulation of the rat may be altered in
      experimental diabetes.

PMID- 9150379
TI  - PGE1-induced arterial thromboresistance is a vascular property as identified by
      cross-perfusion technique.
AB  - Prostaglandin (PG) E1 has been shown to improve thromboresistance. This
      experiment was designed to examine whether an effect on the arterial wall or the
      platelets is responsible for this phenomenon. Using a cross-perfusion model, the
      aortic and iliac artery endothelium of rabbits was removed by a balloon catheter
      before being perfused with blood of donor rabbits. Donor and/or receiver animals
      were treated with 20 microg PGE1 or vehicle (cyclodextrin) intravenously daily
      for 1 week. After the last administration of PGE1 or its vehicle, the animals
      were killed and native blood from a donor rabbit was recirculated (30 ml/min) via
      a deendothelialized segment of a receiver rabbit. The contact (C) and spread (S)
      platelets as well as the denuded surface covered with platelet aggregates (> 5
      microm in height) were quantified by morphometry. Deposition of (111)In-oxine
      labeled autologous platelets was quantitatively determined per surface unit. In
      addition, PGI(2)- and TXB2-formation by the denuded aortic and iliac artery
      segments was determined. Pretreatment of receiver rabbits with PGE1 resulted in
      morphometrically assessed decreased platelet adhesion and aggregation, even when
      the donor rabbit was vehicle-treated. A vehicle-treated receiver rabbit, in
      contrast, shows platelet deposition comparable to controls, even if the donor
      rabbit was PGE1-pretreated. Treatment of donor animals with PGE1 did not result
      in a reduction in thrombogenicity. The beneficial in vivo PGE1 action of
      decreased arterial thrombogenicity is thus mediated by an effect on the vascular
      wall rather than on circulating platelets.

PMID- 9150380
TI  - Prostanoids and free radicals in Cl4C-induced hepatotoxicity in rats: effect of
      astilbin.
AB  - A beneficial effect of flavonoids in Cl(4)C-induced hepatoxicity in rats has been
      reported. In this communication we have evaluated the protective effect of
      astilbin, an active flavonoid isolated from a crude extract of Hymenaea martiana,
      as well as its action on liver arachidonate metabolism in Cl(4)C-treated rats.
      The following groups of rats were studied: Group I = controls; Group II =
      Astilbine-treated animals (40 mg/Kg); Group III = Cl(4)C-treated at 1 ml/kg;
      Group IV = Astilbine + ClC4 and Group V = Vitamine E (50 mg/Kg) + Cl(4)C-treated
      animals. Histological findings, superoxide dismutase activity, lipoperoxides and
      prostanoid profiling studies revealed that the hepatoprotective effect of
      astilbine was higher than that of vitamin E. Astilbine was capable to restore
      lipoperoxides and tissue prostanoids to basal values.

PMID- 9150381
TI  - Differential control of cyclins D1 and D3 and the cdk inhibitor p27Kip1 by
      diverse signalling pathways in Swiss 3T3 cells.
AB  - Quiescent Swiss 3T3 cells can be induced to re-enter the cell cycle by
      stimulation of a variety of growth factor-dependent signal transduction cascades.
      We have utilised this cell system to investigate the point of convergence of
      mitogenic signalling by analysing the changes that distinct mitogens induce in
      the components of the cell cycle regulatory machinery (the G1 cyclins, cdks and
      their inhibitors). In the presence of insulin, activation of cAMP-dependent
      protein kinase caused a dramatic post-transcriptional down-regulation of
      p27(Kip1), an increase in cyclin D3 but had little effect on cyclin D1 levels,
      whilst activation of protein kinase C had a more modest effect on cyclin D3 and
      p27(Kip1) but caused a striking elevation in the expression of cyclin D1. The
      neuropeptide bombesin, when combined with insulin, caused increased expression of
      cyclin D1 and down-regulation of p27(Kip1) mRNA and protein. Thus each
      combination of mitogenic agents had different effects on the components
      responsible for regulating the orderly progression of the cell cycle. This
      outcome is incompatible with a single route to mitogenesis and demonstrates that
      different mitogens remain distinct in the signalling responses they initiate,
      only converging at the levels of the expression of the D-type cyclins and the
      inhibitor p27(Kip1).

PMID- 9150382
TI  - Amino acid residues which distinguish the mitogenic potentials of two FGF
      receptors.
AB  - Fibroblast growth factors mediate cellular responses by interacting with a family
      of related receptor tyrosine kinases (FGFRs). We have previously shown that FGFR
      1, but not of FGFR-4, ectopically expressed in BaF3 lymphoid cells allows for
      proliferation in response to FGFs, and that the intracellular signaling halves of
      these two receptors distinguish their mitogenic potentials (Wang et al., 1994).
      In order to map the residues which functionally distinguish these receptors, a
      panel of chimeric receptors whose cytodomains bear different contributions from
      FGFR-1 and FGFR-4 were constructed and characterized. The behavior of these
      chimeras implicate amino acids from both the kinase insert and kinase domains in
      receptor-mediated proliferation. Specifically, two tyrosine residues present in
      the short kinase insert domain of FGFR-1 and absent from FGFR-4 are a necessary,
      but not sufficient, component of a fully mitogenic receptor, suggesting that
      tyrosine phosphorylation in the kinase insert promotes a mitogenic signaling
      pathway. A strongly mitogenic receptor also requires one or two FGFR-1-specific
      residues from either of two regions within the kinase domain. One of these
      regions is within the kinase domain's activation loop, where FGFR-1, but not FGFR
      4, bears a key aspartate residue. The mitogenic potentials of FGFR-1, FGFR-4, and
      the chimeric receptors strongly correlates with the magnitude of ligand-induced
      receptor autophosphorylation in BaF3 cells. We discuss mechanisms by which these
      few key amino acid differences may determine the levels of ligand-induced FGF
      receptor autophosphorylation and mitogenic potency.

PMID- 9150383
TI  - Cell to substratum adhesion is involved in v-Src-induced cellular protein
      tyrosine phosphorylation: implication for the adhesion-regulated protein tyrosine
      phosphatase activity.
AB  - Protein tyrosine phosphorylation accompanies the integrin-mediated cell to
      substratum adhesion, and is essential for the progression of G1/S phase of the
      cell-cycle in normal fibroblasts. To examine how cellular protein tyrosine
      phosphatase (PTPase) activity is involved in regulating the adhesion-dependent
      protein tyrosine phosphorylation, we employed fibroblast cells bearing an active
      form of a protein tyrosine kinase (PTK), v-Src. We found that the v-Src induced
      tyrosine phosphorylation in certain proteins such as tensin, talin, p120, p80/85
      (cortactin) and paxillin was greatly reduced when the cell to substratum adhesion
      was lost. Readhesion of the cells onto fibronectin restored these phosphorylation
      events, while this was inhibited by the addition of RGD peptide. The kinase
      activity of the v-Src was unchanged by the loss of cell to substratum adhesion.
      On the other hand, treatment with a protein tyrosine phosphatase inhibitor
      vanadate caused much the same increase in the v-Src-mediated cellular tyrosine
      phosphorylation between cells adhered to the culture environments and cells kept
      in suspension. These data suggest that PTPase(s) appears to be more critical than
      the v-Src PTK in determining the cell adhesion-dependent protein tyrosine
      phosphorylation. Moreover, most of the protein tyrosine phosphorylations that are
      mediated by the v-Src but still dependent on the cell adhesion were indeed
      greatly reduced during an anchorage-independent growth of v-Src cells. Thus our
      data collectively indicate that the v-Src induced high level of tyrosine
      phosphorylation in certain types of proteins are still under the control of the
      integrin(s) or the cell adhesion to culture substratum, and most of these
      adhesion-regulated high levels of tyrosine phosphorylations are not essential for
      the transformed phenotype.

PMID- 9150384
TI  - The retinoblastoma gene family is differentially expressed during embryogenesis.
AB  - We report differential expression of the RB1 tumor suppressor gene and the
      homologous genes p107 and p130 during embryogenesis. Abundant RB1 transcripts
      were detected during neurogenesis, hematopoiesis, myogenesis, lens development
      and in the ganglion cell layer of the embryonic retina, prior to and during
      differentiation. The expression pattern of RB1 mirrored the defects in RB1 mutant
      mice (RB-/-). In the heart, lung, kidney and intestine, p107, but not RB1, was
      expressed. In the liver and the central nervous system p107 and RB1 were co
      expressed, consistent with the accelerated cell death observed in RB-/-; p107-/-
      double knock-out mice. In the central nervous system, p107 expression was
      restricted to proliferating cells surrounding the ventricles, while RB1 was
      expressed in areas of both proliferating and differentiating cells. In contrast
      to RB1 and p107, expression of p130 was low throughout embryogenesis. In situ
      hybridization and Western blot analyses showed that the expression of p107 and
      p130 was not markedly altered in RB-/- embryos compared to control littermates.
      Our results suggest that members of RB1 gene family have distinct, but
      overlapping roles in embryogenesis, with p107 and RB1 possibly having redundant
      functions in the central nervous system and liver.

PMID- 9150385
TI  - Frequent inactivation of p16INK4a in oral premalignant lesions.
AB  - Head and neck carcinogenesis is believed to be a multistep process, whereby
      genetic events accumulate in the carcinogen-exposed field at risk, resulting in
      distinct phenotypic premalignant changes that eventually evolve into invasive
      cancer. Frequent loss of heterozygosity (LOH) at the chromosome 9p21 region and
      inactivation of p16(INK4a) by different mechanisms have been described in head
      and neck squamous cell carcinoma (HNSCC). Recently, we reported that loss of 9p21
      is also frequent in oral premalignant lesions. To investigate potential
      inactivation of p16(INK4a) in these premalignant lesions, we analysed 74 biopsies
      from 36 patients by immunohistochemistry (IHC) for expression of the p16 protein.
      Loss of p16 expression was found in 28 (38%) of the lesion biopsies from 17
      patients (47%). LOH at the D9s171, a marker in the 9p21 region, was observed in
      19 lesion biopsies from 12 cases and correlated with absence of p16 by IHC in 11
      (92%) of the 12 comparable cases and 15 (79%) of 19 lesion biopsies. By direct
      sequencing of ten lesion biopsies from ten individuals with LOH at D9s171 for
      p16(INK4a) exon 2, one non-sense mutation at codon 88 (GGA-->TGA) was identified.
      Our data suggest that inactivation of p16(INK4a) may play an important role in
      early head and neck cancer development.

PMID- 9150386
TI  - Constitutive expression of lymphoma-associated NFKB-2/Lyt-10 proteins is
      tumorigenic in murine fibroblasts.
AB  - The NFKB-2 (Lyt-10) gene codes for an NF-kappaB-related transcription factor
      containing rel-polyG-ankyrin domains. Rearrangements of the NFKB-2 locus leading
      to the production of 3' truncated NFKB-2 proteins are recurrently found in
      lymphoid neoplasms, particularly cutaneous lymphomas. Such mutant NFKB-2 proteins
      have lost the ability to repress transcription that is typical of NFKB-2 subunit
      p52, and function as constitutive transcriptional activators. To verify whether
      the expression of abnormal NFKB-2 proteins can lead to malignant transformations
      in mammalian cells, we transfected human lymphoblastoid cell lines and murine
      fibroblasts (Balb/3T3) with expression vectors carrying the cDNAs coding for
      normal NFKB-2p52, Lyt-10C alpha or LB40 proteins, which are representative of the
      abnormal types found in lymphoma cases. The expression of both normal and mutant
      NFKB-2 proteins has a lethal effect on lymphoblastoid cells and a cytotoxic
      effect was also observed in murine fibroblasts. The fibroblast cell lines
      expressing Lyt-10C alpha or LB40, but not those expressing normal NFKB-2p52, were
      capable of forming colonies in soft agar. The analysis of individual clones
      revealed that cloning efficiency correlated with the expression levels of the
      abnormal proteins. Injection of the Lyt-10C alpha-transfected Balb cells in SCID
      mice led to tumor formation in all of the animals, whereas no tumors were
      observed in the mice injected with control or NFKB-2p52-transfected cells, thus
      indicating that abnormal NFKB-2 protein expression is tumorigenic in vivo. Our
      results show that mutant NFKB-2 proteins can lead to the transformed phenotype,
      and support the hypothesis that alterations in NFKB-2 genes may play a role in
      lymphomagenesis.

PMID- 9150387
TI  - The expression of RET and its multiple splice forms in developing human kidney.
AB  - A series of inductive events between two different cell groups, the ureteric bud
      epithelium and metanephric mesenchyme, gives rise to the functional mammalian
      kidney. These reciprocal inductive interactions involve a number of molecules,
      one of which is the RET receptor tyrosine kinase. The phenotype of mice lacking
      functional RET includes kidney agenesis or severe dysgenesis, indicating a
      requirement for RET in kidney organogenesis. To investigate RET expression in
      human kidney development, we used a semi-quantitative RT-PCR-based strategy to
      examine a panel of kidney RNA samples ranging from 8-24 weeks gestational age. We
      found RET expression was highest earlier in development (14 weeks) with
      expression decreasing through to 24 weeks gestation. While three alternative RET
      transcripts generated by exon skipping at the 5' end of the gene were all
      detected throughout kidney development, expression of one transcript, RET2/6,
      where exon 2 was spliced to exon 6, varied relative to full length RET during
      this period. Levels of RET2/6 were highest at the earliest age of fetal kidney
      examined (8 weeks) and decreased relative to all other RET transcripts to low
      adult levels. The period of high expression coincides with a period of rapid bud
      bifurcation. Thus, it is possible that RET2/6 has a role in the early growth and
      differentiation of the human kidney.

PMID- 9150388
TI  - Inhibition of activated Ras-induced neuronal differentiation of PC12 cells by the
      LIM domain of LIM-kinase 1.
AB  - LIM-kinase 1 and 2 (LIMK1 and LIMK2) are members of a novel class of protein
      kinases with structures composed of two LIM motifs at the N-terminus and an
      unusual protein kinase domain at the C-terminus. The cellular functions of the
      LIMK family proteins have remained unknown. In the present study, we examined
      effects of LIMKs on neuronal differentiation of PC12 pheochromocytoma cells.
      Transient expression analyses revealed that LIMK1, in itself, had no apparent
      effect on PC12 cells, but the oncogenic Ras-induced differentiation of PC12 cells
      was notably inhibited by co-expression with LIMK1 or LIMK2. A mutant of LIMK1
      lacking a protein kinase domain (delta K) similarly inhibited Ras-induced
      differentiation of PC12 cells, but a mutant lacking a LIM domain (delta LIM)
      failed to do so, indicating that a LIM domain but not a protein kinase domain is
      required for the inhibitory activity. This notion was further supported by the
      finding that mutation, changing conserved cysteines involved in zinc coordination
      to glycines in both of two LIM motifs, abolished the inhibitory activity of delta
      K. Additionally, we also found that the constitutively activated MAP kinase
      kinase (MAPKK)-induced differentiation of PC12 cells was inhibited by co
      expression with delta K. Furthermore, AK did not inhibit the kinase activity of
      MAP kinase (MAPK) stimulated by MAPKK, when co-expressed in COS7 cells. These
      findings suggest that LIMK1 inhibits neuronal differentiation of PC12 cells,
      through its LIM domain and by interfering with events downstream of MAPK
      activation.

PMID- 9150389
TI  - Regulation of cellular response to cisplatin-induced DNA damage and DNA repair in
      cells overexpressing p185(erbB-2) is dependent on the ras signaling pathway.
AB  - We have examined the role of erbB-2 expression in the modulation of cellular
      toxicity to cisplatin. We have demonstrated that treatment of NIH3T3-erbB-2
      cells, which overexpress the p185(erbB-2) product of the human erbB-2 gene, with
      a monoclonal antibody directed against the extracellular domain (TAb-250),
      results in enhanced cisplatin cytotoxicity. A similar enhancement was obtained
      when cells were exposed to herbimycin A and its analogue CP127 374, both of which
      inhibit tyrosine kinase activity. Using the host cell reactivation (HCR) of
      reporter gene expression from cisplatin-damaged plasmid and unscheduled DNA
      synthesis (UDS) following cisplatin treatment of cells, we have found that
      modulation of erbB-2 by TAb-250 was associated with inhibition of DNA repair. TAb
      250 alone, under conditions which modulate DNA repair, slightly reduces the S
      phase of the cell cycle, while cisplatin induced arrest at S and G2 phases.
      Combination of TAb-250 and cisplatin only slightly prevented cisplatin-induced S
      and G2 blocks. Since the ras pathway is one of the major signaling components
      coupled to erbB-2, we have examined the role of ras in DNA repair regulation.
      Transient expression of a ras dominant negative mutant, Asn-17-ras(H), prevents
      DNA repair modulation by TAb-250, suggesting that the erbB-2 receptor regulates
      DNA repair mechanism(s), at least in part, through ras-coupled pathway(s).

PMID- 9150390
TI  - Influence of Bcl-2 overexpression on the ceramide pathway in daunorubicin-induced
      apoptosis of leukemic cells.
AB  - We have previously demonstrated that daunorubicin (DNR) induces apoptosis in some
      leukemic myeloid cell lines. We investigated a potential protective role for Bcl
      2 in apoptosis induced by DNR in two leukemic cell lines, one myeloid and one
      lymphoid, overexpressing the anti-apoptotic gene Bcl-2. Parental cells treated
      with DNR exhibited classical features of apoptosis 6 h after drug exposure, all
      the cells being dead after 30-48 h. In contrast, overexpression of Bcl-2
      significantly delayed, but did not prevent the occurrence of DNR-induced
      apoptosis, with no surviving cells 96 h after drug exposure. To elucidate the
      mechanism of the protection mediated by Bcl-2, we explored the signaling pathway
      which initiates DNR-induced apoptosis. In this report, we show that, in both the
      myeloid and lymphoid parental cell lines, DNR triggered a sphingomyelin (SM)
      hydrolysis after 10-15 min with a concomitant ceramide generation. Moreover,
      exogenous ceramide induced DNA fragmentation in these cells, with levels similar
      to those observed with DNR treatment. In contrast, Bcl-2 overexpression protected
      the cells against apoptosis induced by ceramide treatment, without preventing the
      early SM hydrolysis nor the ceramide generation in these cells. Our results
      strongly suggest that Bcl-2-mediated protection of DNR-induced apoptosis is
      effected downstream of the SM-ceramide signaling pathway.

PMID- 9150391
TI  - Inactivation of p53 results in high rates of homologous recombination.
AB  - Using a plasmid substrate which integrates into the genome, we determined that
      the rate of homologous recombination was suppressed by p53. Human tumor cell
      lines, mutant or null for p53 had recombination rates 10000-times greater than
      primary fibroblasts. When isogenic cell pairs from tumor cells or primary
      fibroblasts were compared, differing only in one genetic change which inactivated
      p53, the recombination rate increased > 100-fold. Functional inactivation of p53
      by dominant mutant p53, by large T antigen of SV40 virus, by E6 protein of human
      papilloma virus, or by genetic deletion led to the same result. Our results
      suggest that p53 suppresses spontaneous homologous recombination, and that p53 is
      not required for recombination to proceed. The mechanism of recombination
      suppression may be related to the reported association of p53 with Rad 51, but
      the functional consequences of this association are not yet established. It is
      suggested that suppression of homologous recombination is the means by which p53
      maintains genetic stability.

PMID- 9150392
TI  - Tolerance of high levels of wild-type p53 in transformed epithelial cells
      dependent on auto-regulation by mdm-2.
AB  - A significant proportion of human cancers express high levels of p53 protein in
      the absence of an underlying mutation in the gene. Using transformed (Vh1) and
      non-transformed (FRTL-5) rat thyroid epithelial cell lines as a model, we have
      examined the mechanisms by which high levels of wild-type p53 may be tolerated.
      Stable transfection with p53-dependent reporter constructs demonstrated that the
      'excess' wild-type p53 in Vh1 cells is not associated with a comparable increase
      in p53-dependent transcription (though the response to u.v. irradiation is
      retained). Mdm-2, which binds p53 and inhibits its transactivation activity, is
      overexpressed in Vh1 cells in the absence of gene amplification and in a p53
      dependent manner. Furthermore disruption of p53-mdm-2 complex formation in Vh1
      cells by microinjection of an antibody to the p53-binding domain of mdm-2
      resulted in a dramatic increase in p53-dependent transcription. Since only a
      small proportion of the p53 in Vh1 cells was found to be in complex with mdm-2
      (the majority of unbound protein being in a latent form), this suggests that mdm
      2 selectively binds a pool of p53 that would otherwise be active as a sequence
      specific activator of transcription. We suggest that, in some types of tumour,
      the 'sensitivity' of the p53-driven mdm-2 feedback loop may be sufficient to
      prevent free, active p53 reaching the level required for growth arrest or
      apoptosis, making them an ideal target for therapies designed to disrupt p53-mdm
      2 interactions.

PMID- 9150393
TI  - Two functional assays employed to detect an unusual mutation in the
      oligomerisation domain of p53 in a Li-Fraumeni like family.
AB  - Previous investigations of a Li - Fraumeni like family (Barnes et al., 1992)
      demonstrated that both the proband and her mother had elevated p53 protein levels
      in both tumour tissue and normal tissue at sites distant from the tumour,
      although no mutation was found in the p53 gene. In the present study two recently
      described functional assays for p53, an apoptotic assay and the functional assay
      for the separation of alleles in yeast (FASAY), have been employed to study the
      functional activity of p53 from this patient. The results of the apoptotic assay
      demonstrated that this patient had a p53 functional defect and the FASAY result
      suggested that this defect was in fact a germline mutation of the p53 gene. A
      point mutation of codon 337, which results in an amino acid substitution of a
      cysteine for an arginine, was demonstrated initially in cDNA and was confirmed by
      sequencing of genomic DNA. This is an unusual mutation as it is in the
      oligomerisation domain of p53, in contrast to the majority of p53 mutations which
      are in the core DNA binding domain. This mutation results in a protein which
      still retains partial transactivational activity in the FASAY. The mutation of
      codon 337 is only the second reported case of a germline missense mutation
      occurring in the oligomerisation domain of p53.

PMID- 9150394
TI  - Role of p21Waf1/Cip1/Sdi1 in cell death and DNA repair as studied using a
      tetracycline-inducible system in p53-deficient cells.
AB  - Postulated roles for p21(Waf1/Cip1/Sdi1) (p21) in DNA repair and apoptosis remain
      controversial. Studies suggest both stimulatory and inhibitory effects of p21 in
      DNA repair. p21 has also been implicated in induction or protection from
      apoptosis. Using the tetracycline inducible expression system, we studied the
      role of p21 in DNA repair and apoptosis in wild-type p53 deficient DLD1
      colorectal carcinoma cells. These cells displayed marked heterogeneity in their
      ability to tolerate higher levels of exogenous p21. The majority of the p21
      overexpressing cells grew slower and did not exhibit apoptotic phenotype, some
      cells underwent apoptotic death within 5-8 days following p21 induction while
      other became giant cells prior to undergoing cell death. Induction of p21
      transgene neither sensitized to nor protected from adriamycin-induced acute cell
      death. p21 also did not alter the clonogenic survival following adriamycin
      treatment. Clonogenic survival after u.v.-irradiation was, however, increased
      when p21 expression was transiently induced a few hours before and after u.v.
      irradiation. Consistent with its effect on clonogenic survival, p21 also enhanced
      the cellular capacity to repair three different exogenously introduced u.v.
      damaged reporter plasmids. Taken together our results demonstrate that p21 may
      modulate the nucleotide excision repair process to facilitate the repair of u.v.
      type DNA damage even in the absence of wild-type p53.

PMID- 9150395
TI  - Sheared purine x purine pairing in biology.
AB  - The Watson-Crick G x C and A x T base-paired DNA duplex has been the single most
      important milestone in modem molecular biology. However, it is possible that
      other types of stable DNA structures besides the double helix might exist, since
      only about 5% of the human chromosome is transcribed and expressed. Stable, four
      stranded G-tetraplex DNA structures occur in the extensive tandem repeated
      sequences at the telomeres of chromosome. Formation of stable triplexes of the Py
      x Pu x Py or Pu x Pu x Py type have been implicated at the control regions of
      certain human genes. We review and discuss the various types of DNA duplex
      structures containing stable sheared base-pairs and compare their structural
      characteristics with that of B-DNA. Pu x Pu structural motifs are found in the
      highly conserved sequences at the replication origins of several single-stranded
      DNA viruses and in the peri-centromeric regions of human chromosomes, and may be
      involved in important biological functions, such as viral DNA replication and
      centromere formation.

PMID- 9150396
TI  - Fast and slow tracks in lysozyme folding: insight into the role of domains in the
      folding process.
AB  - The folding of lysozyme involves parallel events in which hydrogen exchange
      kinetics indicate the development of persistent structure at very different
      rates. We have monitored directly the kinetics of formation of the native
      molecule by the binding of a fluorescently labelled inhibitor, MeU-diNAG (4
      methylumbelliferyl-N,N'-diacetyl-beta-D-chitobioside). The data show that native
      character monitored in this way also develops with different timescales. Although
      the rate determining step on the slow pathway (approximately 75% of molecules at
      pH 5.5, 20 degrees C) can be attributed to the need to reorganise structure
      formed early in the folding process, the data indicate that the rate determining
      step on the fast track (involving approximately 25% of molecules) involves the
      docking of the two constituent domains of the protein. In the fast folding track
      the data are consistent with a model in which each domain forms persistent
      structure prior to their docking in a locally cooperative manner on a timescale
      comparable to the folding of small single domain proteins.

PMID- 9150397
TI  - Alternative structures of the cauliflower mosaic virus 35 S RNA leader:
      implications for viral expression and replication.
AB  - The CaMV 35 S RNA functions as both messenger and pregenomic RNA under the
      control of its 600 nts leader, which contains regulatory elements involved in
      splicing, polyadenylation, translation, reverse transcription, and probably also
      packaging. The structure of the leader has been characterized theoretically and
      experimentally. The predicted conformation, a low-energy elongated hairpin, base
      pairing the two halves of the leader, with a cross-like structure at the top, is
      strongly supported by enzymatic probing, chemical modification, and phylogenetic
      comparison. The elongated hairpin is stabilized by strong base-pairing between
      the ends of the leader, regions which are important in allowing translation
      downstream of the leader via the ribosome shunt mechanism. At high ionic strength
      the 35 S RNA leader exhibits additional higher order structures of low
      electrophoretic mobility: (1) a long-range pseudoknot connecting central and
      terminal parts of the leader; (2) a dimer. Alternative structures of the CaMV 35
      S RNA leader may co-exist and have specialized functions. Their potential impact
      on CaMV life cycle regulation is discussed.

PMID- 9150398
TI  - Recognition of bacteriophage Qbeta plus strand RNA as a template by Qbeta
      replicase: role of RNA interactions mediated by ribosomal proteins S1 and host
      factor.
AB  - RNA-protein interactions between bacteriophage Qbeta plus strand RNA and the
      components of the Qbeta replicase system were studied by deletion analysis.
      Internal, 5'-terminal and 3'-terminal deletions were assayed for template
      activity with replicase in vitro. Of the two internal binding sites previously
      described for replicase, we found that the S-site (map position 1247 to 1346)
      could be deleted without any significant effect on template activity, whereas
      deletion of the M-site (map position 2545 to 2867) resulted in a strong
      inactivation and a high salt sensitivity of the residual activity. Binding
      complexes of the deletion mutant RNAs with the different proteins involved in
      Qbeta RNA replication were analysed by electron microscopy. The formation of
      looped complex structures, previously reported and explained as simultaneous
      interactions with replicase at the S and the M-site, was abolished by deleting
      the S-site but, surprisingly, not by deleting the M-site. The same types of
      complexes observed with replicase were also formed with purified protein S1 (the
      alpha subunit of replicase), suggesting that these internal interactions with
      Qbeta RNA are mediated by the S1 protein. The Qbeta host factor, a protein
      required for the template activity of the Qbeta plus strand, was reported earlier
      to form similar complexes by binding to the S and M-sites (or adjacent sites) and
      in addition to the 3'-end, resulting in double-looped structures. The patterns of
      looped complexes observed with the deletion mutant RNAs suggest that the binding
      of host factor might not involve the S and M-sites themselves but adjacent
      downstream sites. An additional internal host factor interaction near map
      position 2300 was detected with several mutant RNAs. Qbeta RNA molecules with 3'
      truncations formed 3'-terminal loops with similar efficiency as wild-type RNA,
      indicating that recognition of the 3'-end by host factor is not dependent on a
      specific 3'-terminal base sequence.

PMID- 9150399
TI  - Assessing the reliability of RNA folding using statistical mechanics.
AB  - We have analyzed the base-pairing probability distributions of 16 S and 16 S
      like, and 23 S and 23 S-like ribosomal RNAs of Archaea, Bacteria, chloroplasts,
      mitochondria and Eukarya, as predicted by the partition function approach for RNA
      folding introduced by McCaskill. A quantitative analysis of the reliability of
      RNA folding is done by comparing the base-pairing probability distributions with
      the structures predicted by comparative sequence analysis (comparative
      structures). We distinguish two factors that show a relationship to the
      reliability of RNA minimum free energy structure. The first factor is the
      dominance of one particular base-pair or the absence of base-pairing for a given
      base within the base-pairing probability distribution (BPPD). We characterize the
      BPPD per base, including the probability of not base-pairing, by its Shannon
      entropy (S). The S value indicates the uncertainty about the base-pairing of a
      base: low S values result from BPPDs that are strongly dominated by a single base
      pair or by the absence of base-pairing. We show that bases with low S values have
      a relatively high probability that their minimum free energy (MFE) structure
      corresponds to the comparative structure. The BPPDs of prokaryotes that live at
      high temperatures (thermophilic Archaea and Bacteria) have, calculated at 37
      degrees C, lower S values than the BPPDs of prokaryotes that live at lower
      temperatures (mesophilic and psychrophilic Archaea and Bacteria). This reflects
      an adaptation of the ribosomal RNAs to the environmental temperature. A second
      factor that is important to consider with regard to the reliability of MFE
      structure folding is a variable degree of applicability of the thermodynamic
      model of RNA folding for different groups of RNAs. Here we show that among the
      bases that show low S values, the Archaea and Bacteria have similar, high
      probabilities (0.96 and 0.94 in 16 S and 0.93 and 0.91 in 23 S, respectively)
      that the MFE structure corresponds to the comparative structure. These
      probabilities are lower in the chloroplasts (16 S 0.91, 23 S 0.79), mitochondria
      (16 S-like 0.89, 23 S-like 0.69) and Eukarya (18 S 0.81, 28 S 0.86).

PMID- 9150400
TI  - Phenotypic heterogeneity of mutational changes at a conserved nucleotide in 16 S
      ribosomal RNA.
AB  - RNA sites that contain unpaired or mismatched nucleotides can be interaction
      sites for other macromolecules. C1054, a virtually universally conserved
      nucleotide in the 16 S (small subunit) ribosomal RNA of Escherichia coli, is part
      of a highly conserved bulge in helix 34, which has been located at the decoding
      site of the ribosome. This helix has been implicated in several translational
      events, including peptide chain termination and decoding accuracy. Here, we
      observed interesting differences in phenotype associated with the three base
      substitutions at, and the deletion of, nucleotide C1054. The phenotypes examined
      include suppression of nonsense codons on different media and at different
      temperatures, lethality conditioned by temperature and level of expression of the
      mutant rRNA, ribosome profiles upon centrifugation through sucrose density
      gradients, association of mutant 30 S subunits with 50 S subunits, and effects on
      the action of tRNA suppressor mutants. Some of our findings contradict previously
      reported properties of individual mutants. Particularly notable is our finding
      that the first reported 16 S rRNA suppressor of UGA mutations was not a C1054
      deletion but rather the base substitution C1054A. After constructing deltaC1054
      by site-directed mutagenesis, we observed, among other differences, that it does
      not suppress any of the trpA mutations previously reported to be suppressed by
      the original UGA suppressor. In general, our results are consistent with the
      suggestion that the termination codon readthrough effects of mutations at
      nucleotide 1054 are the result of defects in peptide chain termination rather
      than of decreases in general translational accuracy. The phenotypic heterogeneity
      associated with different mutations at this one nucleotide position may be
      related to the mechanisms of involvement of this nucleotide, the two-nucleotide
      bulge, and/or helix 34 in particular translational events. In particular,
      previous indications from other laboratories of conformational changes associated
      with this region are consistent with differential effects of 1054 mutations on
      RNA-RNA or RNA-protein interactions. Finally, the association of a variety of
      phenotypes with different changes at the same nucleotide may eventually shed
      light on speculations about the coevolution of parts of ribosomal RNA with other
      translational macromolecules.

PMID- 9150401
TI  - Folding of the presequence of yeast pAPI into an amphipathic helix determines
      transport of the protein from the cytosol to the vacuole.
AB  - To investigate the role of the 17 residues long presequence (p17) in the
      transport of the precursor of yeast API (pAPI) from the cytosol to the vacuole we
      have studied the effects of point mutations upon its conformation and on the
      process of transport. 1H NMR analysis of p17 indicates that in aqueous solution
      26% of the molecules have the 4-12 segment folded into an helix. The hydrophobic
      environment provided by SDS micelles promotes the folding of 54% of the p17
      molecules into a 5-16 amphipathic alpha-helix. Both Schiffer-Edmunson helical
      wheel analysis of segment 4-12 and residue hydrophobic moments calculated
      considering all possible side-chain orientations between 80 and 120 degrees,
      indicate the amphipathic character of the helixes assembled in water and
      detergent. Charge interactions between the dipole pairs N-Glu2Glu3 and C
      Lys12Lys13 are essential for helix stability and condition pAPI transport.
      Substitution of either Pro2Pro3 or Lys2Lys3 for Glu2Glu3, results in moderate
      destabilization of the helix, decreases protein targeting to the vacuolar
      membrane and partly inhibits translocation of the protein to the vacuolar lumen.
      Replacement of either Pro12Pro13 or Glu12Glu13 for Lys12Lys13, causes a major
      disruption of the helix, decreases protein targeting and blocks completely the
      translocation of the protein to the vacuolar lumen. Replacement of Gly7 for Ile7,
      a substitution which is known to destabilize alpha-helixes in peptides and
      proteins as a result of the peptide bond to the solvent at Gly residues, produces
      similar effects as the substitutions for the K12K13 pair. The effects of Gly7 on
      helix stability and protein transport are partly reversed by introduction of Asp
      residues at positions 2 and 3 and Ala at position 4. Replacements such as Arg2
      for Glu2, or Arg6 for Glu6, which change the net and local charges of the
      presequence without altering its conformation, have no effect on the protein
      transport. These results provide direct evidence of the involvement of the
      presequence in the transport of pAPI from the cytosol to the vacuole. They show
      that folding of the pAPI presequence is conditioned by the physical/chemical
      properties of the environment and is critical for targeting the protein to the
      vacuolar membrane and for its translocation to the vacuolar lumen.

PMID- 9150402
TI  - The membrane topology of the fusion peptide region of influenza hemagglutinin
      determined by spin-labeling EPR.
AB  - Hemagglutinin (HA) is a homotrimeric surface glycoprotein of the influenza virus.
      In infection, it induces membrane fusion between viral and endosomal membranes at
      low pH. Each monomer consists of the receptor-binding HA1 domain and the membrane
      interacting HA2 domain. It has been known that the NH2-terminal region of the HA2
      domain, the so-called "fusion peptide", inserts into the target membrane and
      plays a crucial role in triggering fusion between the viral and endosomal
      membranes. A major portion of the HA2 domain (FHA2: aa 1 to 127) of influenza
      virus X-31, including the NH2-terminal fusion peptide region, was expressed in
      Escherichia coli. Through site-directed mutagenesis, eight cysteine (Cys) mutants
      in the fusion peptide region of HA2 (A5C, I6C, A7C, G8C, I10C, N12C, G13C, W14C)
      were generated and modified with a nitroxide spin label. Using spin-labeling
      electron paramagnetic resonance (EPR) techniques, we investigated the
      conformation, membrane topology and the local oligomeric state of the fusion
      peptide region in the membrane. EPR spectra showed that this region is likely to
      exist as a flexible monomer in the membrane at both neutral and fusogenic pH
      conditions. In addition, EPR power saturation methods allowed us to measure the
      depth in the membrane of the spin label at each mutation site. The resulting
      depth profile is consistent with an alpha-helix tilted approximately 25 degrees
      from the horizontal plane of the membrane with a maximum depth of 15 A from the
      phosphate group. The tilt and rotational orientation correlates well with a
      calculated amphiphilicity of this region.

PMID- 9150403
TI  - Crystal structure of an alternating octamer r(GUAUGUA)dC with adjacent G x U
      wobble pairs.
AB  - The crystal structure of the RNA duplex, r(GUAUGUA)dC, with a 3'-terminal deoxy C
      residue, has been determined at 1.38 A resolution. The r(GUAUGU) hexameric
      consensus sequence is present at the exon-intron junction in pre-mRNAs of yeast
      and higher eukaryotic organisms. The crystal belongs to the rhombohedral space
      group R3. The hexagonal unit cell dimensions are a = b = 39.71 A, c = 68.15 A and
      gamma = 120 degrees with one duplex in the asymmetric unit. The structure was
      solved using the molecular replacement method. The final model contains 332 atoms
      of the duplex and 67 solvent molecules. The R-factor is 17.6% (Rfree of 23.1%)
      for 4035 reflections with F > or = 1.5sigma(F) in the resolution range 10.0 to
      1.38 A. The duplex is of the A-type with a pseudodyad relating the two strands.
      The RNA helix is slightly distorted, in spite of the presence of two adjacent G x
      U wobble base-pairs located at the center of the helix. The twist angle between
      the wobble pairs, 38.1 degrees, is above the average value and those between the
      wobble base-pairs and the flanking Watson-Crick base-pairs, 26.7 degrees and 26.3
      degrees, respectively, are lower than the average values. The twist between the
      junction base-pairs are about 24 degrees. The G x U wobble pairs are bridged by
      water molecules and solvated in the grooves. G x U base-pairs are as stable as
      the Watson-Crick A x U pairs and only slightly less stable than the G x C pairs
      accounting for their frequent occurrence in RNA.

PMID- 9150404
TI  - Crystal structures of the side-by-side binding of distamycin to AT-containing DNA
      octamers d(ICITACIC) and d(ICATATIC).
AB  - To understand the recognition interactions between AT-containing alternating DNA
      and minor groove binding drugs, the crystal structures of the side-by-side
      binding of two distamycin molecules to the DNA octamers d(ICITACIC)2 and
      d(ICATATIC)2, referred to here as TA and ATAT, respectively, have been determined
      at 1.6 A and 2.2 A, respectively. Compared to the previous 2:1 all-IC
      d(ICICICIC)2-distamycin complex, the substitutions of the I x C base-pairs by the
      A x T base-pairs enable the interactions of the drug with its natural target to
      be studied. Both complexes assume side-by-side drug binding, isomorphous to the
      all IC counterpart in the tetragonal space group P4(1)22 (a = b = 28.03 A, c =
      58.04 A and a = b = 27.86 A, c = 58.62 A, respectively). The ATAT complex also
      crystallized in a new polymorphic monoclinic space group C2 (a = 33.38 A, b =
      25.33 A, c = 28.11 A and beta = 120.45 degrees) and was solved at 1.9 A
      resolution. The structures of the three double drug x DNA complexes are very
      similar, characterized by systematic hydrogen bonding and van der Waals
      interactions. Each drug hydrogen bonds with the bases of the proximal DNA strand
      only and stacks with the sugar moiety, while the side-by-side drugs themselves
      exhibit pyrrole ring-peptide stacking. The pyrrole-peptide interaction is crucial
      for the side-by-side binding mode of the distamycin/netropsin family of drugs.
      The purine-pyrimidine alternation is probably responsible for the striking
      alternation in the helical and backbone conformations. The structures are
      conserved between the pure IC complex and the AT substituted complexes but
      further details of the side-by-side binding to DNA are provided by the 1.6 A
      resolution structure of TA.

PMID- 9150405
TI  - Nine polymorphic crystal structures of d(CCGGGCCCGG), d(CCGGGCCm5CGG),
      d(Cm5CGGGCCm5CGG) and d(CCGGGCC(Br)5CGG) in three different conformations:
      effects of spermine binding and methylation on the bending and condensation of A
      DNA.
AB  - The A-DNA decamer d(CCGGGCCm5CGG) crystallizes in the presence of spermine in
      three polymorphic forms and with one duplex in the asymmetric unit: hexagonal
      (P6(1)), unit cell of 55.0 A x 55.0 A x 45.9 A; orthorhombic (P2(1)2(1)2(1)),
      unit cell of 24.8 A x 44.6 A x 48.0 A, and a second orthorhombic (P2(1)2(1)2(1)),
      unit cell of 23.6 A x 40.8 A x 43.4 A. The reduction in cell volume among the
      three different forms is accompanied by a large reduction in solvent content (67%
      versus 40% versus 24%) and a significant reduction in volume per base-pair (2005
      A(3) versus 1325 A(3) versus 1048 A(3)). There is also a concomitant increase in
      the number of bound spermine molecules per duplex (0 versus 1 versus 2) as well
      as an increase in DNA bending (10 degrees versus 16 degrees versus 31 degrees),
      which correspond to major groove widths of 8.0 A versus 4.5 A versus 1.3 A,
      respectively. The P6(1) crystal form, which represents a new space group for A
      DNA decamers, supports one of the most hydrated and extended DNA duplexes to
      date, while the second orthorhombic form supports one of the least-hydrated and
      most-condensed non-Z-DNA duplexes. The unmethylated analogue d(CCGGGCCCGG), the
      double-methyl derivative d(Cm5CGGGCCm5CGG) and the bromine derivative
      d(CCGGGCC(Br)5CGG) also crystallize in at least two of the aforementioned
      conformations, and all nine crystal structures were determined. We report, in
      detail, on the three crystal structures of d(CCGGGCCm5CGG) and the effects of
      methylation and spermine binding on A-DNA conformation.

PMID- 9150406
TI  - Thermodynamics of the interactions of lac repressor with variants of the
      symmetric lac operator: effects of converting a consensus site to a non-specific
      site.
AB  - What are the thermodynamic consequences of the stepwise conversion of a highly
      specific (consensus) protein-DNA interface to one that is nonspecific? How do the
      magnitudes of key favorable contributions to complex stability (burial of
      hydrophobic surfaces and reduction of DNA phosphate charge density) change as the
      DNA sequence of the specific site is detuned? To address these questions we
      investigated the binding of lac repressor (LacI) to a series of 40 bp fragments
      carrying symmetric (consensus) and variant operator sequences over a range of
      temperatures and salt concentrations. Variant DNA sites contained symmetrical
      single and double base-pair substitutions at positions 4 and/or 5 [sequence: see
      text] in each 10 bp half site of the symmetric lac operator (Osym). Non-specific
      interactions were examined using a 40 bp non-operator DNA fragment. Disruption of
      the consensus interface by a single symmetrical substitution reduces the observed
      equilibrium association constant (K(obs)) for Osym by three to four orders of
      magnitude; double symmetrical substitutions approach the six orders in magnitude
      difference between specific and non-specific binding to a 40 bp fragment. At
      these adjacent positions in the consensus site, the free energy effects of
      multiple substitutions are non-additive: the first reduces /deltaG(obs)o/ by 3 to
      5 kcal mol(-1), approximately halfway to the non-specific level, whereas the
      second is less deleterious, reducing /deltaG(obs)o/ by less than 3 kcal mol(-1).
      Variant-specific dependences of K(obs) on temperature and salt concentration
      characterize these LacI-operator interactions. In general, binding constants and
      standard free energies of binding both exhibit characteristic extrema near 290 K.
      As a consequence, both the enthalpic and entropic contributions to stability of
      Osym and variant complexes change from positive (i.e. entropy driven) at lower
      temperatures to negative (i.e. enthalpy driven) at higher temperatures,
      indicating that the heat capacity change upon binding, deltaC(obs)o, is large and
      negative. In general, /deltaC(obs)o/ decreases as the specificity and stability
      of the variant complex decreases. Stabilities of complexes of LacI with Osym and
      all variant operators are strongly [salt]-dependent. Binding constants for the
      variant complexes exhibit a power-dependence on [salt] that is larger in
      magnitude (i.e. more negative) than for Osym, but no obvious trend relates
      changes in contributions from the polyelectrolyte effect and the observed
      reductions in stability (delta deltaG(obs)o). These variant-specific
      thermodynamic signatures provide novel insights into the consequences of
      converting a consensus interface to a less specific one; such insights are not
      obtained from comparisons at the level of delta deltaG(obs)o. We propose that
      this variant-specific behavior arises from a strong effect of operator sequence
      on the extent of induced conformational changes in the protein (and possibly also
      in the DNA site) which accompany binding.

PMID- 9150407
TI  - Three-dimensional structure of an Fab-peptide complex: structural basis of HIV-1
      protease inhibition by a monoclonal antibody.
AB  - F11.2.32, a monoclonal antibody raised against HIV-1 protease (Kd = 5 nM), which
      inhibits proteolytic activity of the enzyme (K(inh) = 35(+/-3)nM), has been
      studied by crystallographic methods. The three-dimensional structure of the
      complex between the Fab fragment and a synthetic peptide, spanning residues 36 to
      46 of the protease, has been determined at 2.2 A resolution, and that of the Fab
      in the free state has been determined at 2.6 A resolution. The refined model of
      the complex reveals ten well-ordered residues of the peptide (P36 to P45) bound
      in a hydrophobic cavity at the centre of the antigen-binding site. The peptide
      adopts a beta hairpin-like structure in which residues P38 to P42 form a type II
      beta-turn conformation. An intermolecular antiparallel beta-sheet is formed
      between the peptide and the CDR3-H loop of the antibody; additional polar
      interactions occur between main-chain atoms of the peptide and hydroxyl groups
      from tyrosine residues protruding from CDR1-L and CDR3-H. Three water molecules,
      located at the antigen-antibody interface, mediate polar interactions between the
      peptide and the most buried hypervariable loops, CDR3-L and CDR1-H. A comparison
      between the free and complexed Fab fragments shows that significant
      conformational changes occur in the long hypervariable regions, CDR1-L and CDR3
      H, upon binding the peptide. The conformation of the bound peptide, which shows
      no overall structural similarity to the corresponding segment in HIV-1 protease,
      suggests that F11.2.32 might inhibit proteolysis by distorting the native
      structure of the enzyme.

PMID- 9150408
TI  - Characterization of NADP+ binding to perdeuterated MurB: backbone atom NMR
      assignments and chemical-shift changes.
AB  - Backbone-atom resonances have been assigned for both the substrate-free and the
      NADP+-complexed forms of UDP-N-acetylenolpyruvylglucosamine reductase (MurB), a
      monomeric, 347-residue (38.5 kDa) flavoenzyme essential for bacterial cell-wall
      biosynthesis. NMR studies were performed using perdeuterated, uniformly 13C/15N
      labeled samples of MurB. In the case of substrate-free MurB, one or more backbone
      atoms have been assigned for 334 residues (96%). The assigned backbone atoms
      include 309 1HN and 15N atoms (94%), 315 13CO atoms (91%), 331 13C(alpha) atoms
      (95%), and 297 13C(beta) atoms (93%). For NADP+-complexed MurB, one or more
      backbone atoms have been assigned for 313 residues (90%); these include 283 1HN
      and 15N atoms (86%), 305 13CO atoms (88%), 310 13C(alpha) atoms (89%), and 269
      13C(beta) atoms (84%). The strategies used for obtaining resonance assignments
      are described in detail. Information on the secondary structure in solution for
      both the substrate-free and NADP+-complexed forms of the enzyme has been derived
      both from 13C(alpha) and 13C(beta) chemical-shift deviations from random-coil
      values and from 1HN-1HN NOEs. These data are compared to X-ray crystallographic
      structures of substrate-free MurB and MurB complexed with the UDP-N
      acetylglucosamine enolpyruvate (UNAGEP) substrate. NADP+ binding induces
      significant chemical-shift changes in residues both within the known UNAGEP and
      FAD binding pockets and within regions known to undergo conformational changes
      upon UNAGEP binding. The NMR data indicate that NADP+ and UNAGEP utilize the same
      binding pocket and, furthermore, that the binding of NADP+ induces structural
      changes in MurB. Finally, many of the residues within the UNAGEP/NADP+ binding
      pocket were difficult to assign due to dynamic processes which weaken and/or
      broaden the respective resonances. Overall, our results are consistent with MurB
      having a flexible active site.

PMID- 9150409
TI  - Site-directed mutagenesis of active site contact residues in a hydrolytic abzyme:
      evidence for an essential histidine involved in transition state stabilization.
AB  - Specific molecular interactions involved in catalysis by antibody 6D9 were
      investigated by site-directed mutagenesis. The catalytic antibody 6D9, which was
      generated against a transition state analog (III), hydrolyzes a non-bioactive
      chloramphenicol monoester derivative (I) to produce chloramphenicol (II).
      Construction of a three-dimensional molecular model of 6D9 and sequence
      comparison within a panel of related antibodies suggested candidates for
      catalytic residues, His (L27d), Tyr (L32), Tyr (H58) and Arg (H100b); these were
      targeted for the site-directed mutagenesis study. The Y-H58-F and R-H100b-A
      mutants possessed catalytic activities comparable to that of the wild-type, and
      the Y-H58-H and Y-L32-F mutant displayed an approximately fivefold decrease in
      k(cat)/Km. In the transition state analysis, the plots of logK(TSA) versus
      log(k(cat)/Km) for the mutants are linear, with a slope of approximately 1.0,
      indicating that the entire hapten-binding energy in the mutants is also utilized
      to bind the transition state and to accelerate the catalysis. In addition, a
      dramatic change in the catalytic activity was observed when the histidine residue
      (27d) in the CDR1 light chain was replaced with alanine. The H-L27d-A mutant had
      no detectable catalytic activity. This mutation led to a large, 40-fold reduction
      in transition state binding, with no change in substrate binding. Coupled with
      the previous kinetic studies and chemical modifications of the intact 6D9
      antibody, this mutagenesis study has demonstrated that His L27d plays an
      essential role in stabilization of the transition state, the mechanism of
      catalysis by the 6D9 antibody.

PMID- 9150410
TI  - Two complementary methods for predicting peptides binding major
      histocompatibility complex molecules.
AB  - Peptides that bind to major histocompatibility complex products (MHC) are known
      to exhibit certain sequence motifs which, though common, are neither necessary
      nor sufficient for binding: MHCs bind certain peptides that do not have the
      characteristic motifs and only about 30% of the peptides having the required
      motif, bind. In order to develop and test more accurate methods we measured the
      binding affinity of 463 nonamer peptides to HLA-A2.1. We describe two methods for
      predicting whether a given peptide will bind to an MHC and apply them to these
      peptides. One method is based on simulating a neural network and another, called
      the polynomial method, is based on statistical parameter estimation assuming
      independent binding of the side-chains of residues. We compare these methods with
      each other and with standard motif-based methods. The two methods are
      complementary, and both are superior to sequence motifs. The neural net is
      superior to simple motif searches in eliminating false positives. Its behavior
      can be coarsely tuned to the strength of binding desired and it is extendable in
      a straightforward fashion to other alleles. The polynomial method, on the other
      hand, has high sensitivity and is a superior method for eliminating false
      negatives. We discuss the validity of the independent binding assumption in such
      predictions.

PMID- 9150411
TI  - Prediction of protein side-chain rotamers from a backbone-dependent rotamer
      library: a new homology modeling tool.
AB  - Modeling by homology is the most accurate computational method for translating an
      amino acid sequence into a protein structure. Homology modeling can be divided
      into two sub-problems, placing the polypeptide backbone and adding side-chains.
      We present a method for rapidly predicting the conformations of protein side
      chains, starting from main-chain coordinates alone. The method involves using
      fewer than ten rotamers per residue from a backbone-dependent rotamer library and
      a search to remove steric conflicts. The method is initially tested on 299 high
      resolution crystal structures by rebuilding side-chains onto the experimentally
      determined backbone structures. A total of 77% of chi1 and 66% of chi(1 + 2)
      dihedral angles are predicted within 40 degrees of their crystal structure
      values. We then tested the method on the entire database of known structures in
      the Protein Data Bank. The predictive accuracy of the algorithm was strongly
      correlated with the resolution of the structures. In an effort to simulate a
      realistic homology modeling problem, 9424 homology models were created using
      three different modeling strategies. For prediction purposes, pairs of structures
      were identified which shared between 30% and 90% sequence identity. One strategy
      results in 82% of chi1 and 72% chi(1 + 2) dihedral angles predicted within 40
      degrees of the target crystal structure values, suggesting that movements of the
      backbone associated with this degree of sequence identity are not large enough to
      disrupt the predictive ability of our method for non-native backbones. These
      results compared favorably with existing methods over a comprehensive data set.

PMID- 9150412
TI  - Dextromethorphan protects against cerebral injury following transient, but not
      permanent, focal ischemia in rats.
AB  - Dextromethorphan (DM) has been observed to afford neuroprotection in a variety of
      in vitro and in vivo experimental models of CNS injury. We have evaluated the
      neuroprotective activity of DM following both transient (2 h) and permanent focal
      cerebral ischemia in the rat. Middle cerebral artery occlusion (MCAO) was
      produced in male Sprague-Dawley rats using the intraluminal filament technique.
      Animals were dosed s.c with 20 mg/kg DM at 0.5, 1, 2, 4, and 6 hours post
      occlusion. Analysis of brain injury was performed 24 hours after permanent
      occlusion or reperfusion. Following transient MCAO, vehicle treated rats
      exhibited a total infarct volume of 203 +/- 33 mm3. DM produced a 61% reduction
      in infarct volume to 79 +/- 13 mm3. Permanent MCAO produced a larger infarct
      volume (406 +/- 44 mm3) which was not significantly reduced in size by treatment
      with DM (313 +/- 58 mm3). Infarcted hemispheric oedema was not different in
      vehicle treated rats following transient or permanent MCAO and was not reduced by
      DM in either group. Following transient MCAO, rectal temperature was elevated 1,2
      and 5 hours post occlusion. While not inducing hypothermia or altering
      physiological parameters such as blood pressure and blood gases, DM attenuated
      this injury-related increase in temperature, an effect which appeared to
      correlate with its ability to protect neurons in temperature regulating
      hypothalamic centres. The DM-induced reduction in infarction demonstrated in our
      model of transient focal cerebral ischemia provides further support for the in
      vivo neuroprotective activity of this compound. Importantly, these data
      demonstrate the limited neuroprotective efficacy of DM when attempting to combat
      more severe focal ischemic injuries and imply that drug-induced hypothermia is
      not ultimately responsible for its protective action.

PMID- 9150413
TI  - Endogenous codeine and morphine in anorexia and bulimia nervosa.
AB  - The endogenous plasma alkaloids codeine and morphine were shown to be elevated in
      patients with anorexia nervosa and bulimia nervosa compared to control subjects.
      The role of these opioids in the pathophysiology of these eating disorders is
      discussed in relation to an auto-addiction opioid model. This model proposes that
      endogenous opioids are released during an initial period of dieting and reinforce
      a state of starvation dependence [1,2].

PMID- 9150415
TI  - Effects of triamcinolone on brain and cerebrospinal fluid apolipoprotein E levels
      in rats.
AB  - The effects of the short term administration of triamcinolone (0.5 mg per 100 g
      body weight, 5 days) on apolipoprotein E and A-I concentrations in cerebrospinal
      fluid (CSF), brain extract and serum were studied in male Wistar rats using
      enzyme immunoassays. ApoE was significantly increased by triamcinolone in apoE
      rich HDL1 in serum; 40+/-13 (mean+/-SD) vs. 68+/-23 mg/dl (15 saline-treated rats
      vs. 11 triamcinolone-treated rats)(P<0.01), which was paralleled by an increase
      in serum apoA-I (76+/-21 vs. 184+/-24 mg/dl), while serum lipids also increased
      significantly. No significant difference was observed in the apoE concentrations
      in CSF (296+/-170 vs. 269+/-67 microg/dl) or brain extract (5.0+/-1.6 vs. 5.7+/
      1.8 microg/g wet weight). The apoA-I concentrations found in CSF and brain
      extract were much lower than those for apoE and were not appreciably affected by
      triamcinolone: 7.7+/-5.5 vs. 4.5+/-3.1 microg/dl for CSF and <0.5 vs. <0.5
      microg/g wet weight for brain extract. The apo E metabolism in the rat central
      nervous system appears to be refractory to the short term administration of
      triamcinolone and to changes in the serum lipoprotein metabolism. ApoA-I appears
      unlikely to play a significant role in the rat central nervous system.

PMID- 9150414
TI  - Influence of endothelium in contraction induced by phorbol ester in isolated rat
      aortic rings.
AB  - The present study aimed to investigate the possible role of endothelium in
      contractile response to phorbol 12,13-diacetate (PDA) by measuring the
      contractile force in rat isolated aortic rings. PDA at low concentrations induced
      small and sustained tension in arteries with intact endothelium. N(G)-Nitro-L
      arginine (100 microM), a nitric oxide synthase inhibitor and methylene blue (10
      microM), an O2-generator induced a large increase in tension in the presence of
      PDA. The magnitude of contractions in response to N(G)-Nitro-L-arginine was
      related to concentrations of PDA. Staurosporine (10 nM), an inhibitor of protein
      kinase C completely inhibited contractile response to PDA as well as potentiating
      effects of N(G)-Nitro-L-arginine and methylene blue. Removal of the endothelium
      abolished contractile responses to both N(G)-Nitro-L-arginine and methylene blue
      in the presence of PDA. Removal of extracellular Ca2+ suppressed contractile
      responses to both PDA and N(G)-Nitro-L-arginine. On the other hand, N(G)-Nitro-L
      arginine (100 microM) did not induce contractions of the rat aorta pre-treated
      with 4-alpha-phorbol 12-myristate 13-acetate, an inactive form of phorbol ester.
      Acetylcholine concentration-dependently induced reduction of tension induced by
      PDA (0.3 microM) in rat aorta. N(G)-Nitro-L-arginine or removal of endothelium
      prevented the effect of the acetylcholine-induced relaxation. Indomethacin (1
      microM), glibenclamide (3 microM) and charybdotoxin (100 nM) did not affect the
      PDA response in rat aorta. These results indicate that in rat aorta, the basal
      release of nitric oxide could modulate the PDA-induced contraction, which is
      likely to accounts for the smaller contractile response induced by PDA in
      arteries with intact endothelium compared to much larger contractions seen in
      arteries without endothelium.

PMID- 9150416
TI  - Production of adrenomedullin in human vascular endothelial cells.
AB  - To examine the production of adrenomedullin (AM) in human vascular endothelial
      cells, AM concentrations in cultured endothelial cells derived from the human
      umbilical vein and the conditioned media of the cells were measured in the
      present study. The cultured endothelial cells secreted immunoreactive AM (ir-AM)
      into the medium at a rate of 14.7 +/- 3.0 fmol/10(6) cells/24 h with an
      intracellular ir-AM of 5.2 +/- 0.8 fmol/l0(6) cells. Analysis by reverse phase
      high performance-liquid chromatography (HPLC) showed that ir-AM in both the cells
      and the conditioned medium eluted at the position identical to that of human AM(1
      52). Treatment with dexamethasone significantly augmented the secretion of ir-AM
      from the cells without any effect on the intracellular ir-AM concentration.
      Northern blot analysis showed not only the presence of the 1.6 kb human AM
      precursor mRNA in the endothelial cells, but also its increased expression in the
      dexamethasone-treated cells. Thus, AM was synthesized and secreted by the human
      endothelial cells of the umbilical vein, and glucocorticoid augmented the AM
      production. These findings suggest not only the role of AM as a local modulator
      of the vascular tone but also the possibility that endothelial cells contribute
      to circulating AM in the human blood.

PMID- 9150417
TI  - Effect of route and frequency of administration of apomorphine on growth hormone
      release in African catfish (Clarias gariepinus).
AB  - Apomorphine is known to stimulate growth hormone release in African catfish
      following an intraperitoneal (IP) injection. In the present study the effect of
      apomorphine (5 or 20 mg/kg body weight) on plasma GH levels was evaluated after
      gastro-intestinal or parenteral delivery. Apomorphine increased the plasma GH
      concentration regardless of the route of administration, indicating that
      apomorphine can be absorbed from the intestinal tract. The effect of repeated
      administration of apomorphine differed clearly between the tested doses. Although
      a single IP injection with 20 mg apomorphine/kg body weight resulted in a clear
      increase in plasma GH levels, a second injection given 12 hours later was
      ineffective. In contrast the last of 4 consecutive injections with 5 mg
      apomorphine/kg body weight given at intervals of 12 hours stimulated the plasma
      GH levels in a similar way to a single IP injection with the same dose.

PMID- 9150418
TI  - Uric acid changes in serum during different forms of hepatic vascular inflow
      occlusion.
AB  - The present study was conducted to develop an efficient marker which can evaluate
      the influence of the occlusion of hepatic vascular inflow, which technique is
      commonly used in major liver surgery or in liver transplantation. Serum samples
      from the rats induced by hepatic vascular inflow occlusion were analyzed with
      high performance liquid chromatography with the electrochemical detection, and a
      substance which changed in accordance with the duration of the occlusion was
      obtained. Both the retention time and the ultraviolet absorption spectra of the
      substance completely agreed with those of an authentic uric acid and the
      substance was ultimately determined to be uric acid. To evaluate the changes in
      serum uric acid during different forms of hepatic vascular inflow occlusion we
      devised the four types of experimental model, viz. the occlusion of hepatic
      artery, portal vein, both hepatic artery and portal vein and both hepatic artery
      and portal vein of left hepatic lobes. From the device of experiments our results
      indicated that in the early stage of hepatic vascular inflow occlusion the high
      values of serum uric acid did not reflect the damage of hepatic circulation but
      rather responded to the intestinal congestion. Our results also indicated that
      even after the declamping of hepatic vascular inflow if high values of serum uric
      acid are prolonged it means the deterioration of the portocaval circulation
      including both intestinal and hepatic circulation. So that the evaluation of the
      severity of injured liver due to hepatic vascular inflow occlusion should be done
      with the caution especially in vivo study when uric acid values are used as a
      marker.

PMID- 9150419
TI  - Polyamine transport systems of Leishmania donovani promastigotes.
AB  - The following observations are conjointly indicative of the presence of distinct
      energy-dependent, saturable and multiple polyamine transport systems in
      Leishmania donovani promastigotes, the causative agent for visceral
      leishmaniasis. Spermidine was influxed with as much as seven times higher rate
      than putrescine, while both spermidine and putrescine transporters exhibited
      equally high affinity for the respective polyamine. N-Ethylmaleimide arrested the
      complete functionality of both the transporters which could be restored by
      reduced glutathione. Putrescine transporter did not recognize spermine but
      spermidine was recognized to some extent, while spermidine transporter
      significantly recognized spermine but putrescine was absolutely spared. A few
      aromatic diamines viz., diaminobiphenyl and the analogs as well as aliphatic
      diamines viz., cadaverine and agmatine were selectively recognized by the
      putrescine transporter only. L. donovani promastigotes grown in presence of alpha
      difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase,
      registered marked upregulation of putrescine transport while spermidine transport
      was only marginally induced. PA transport systems provide the alternative pool of
      polyamines in L. donovani promastigotes in the absence of an adequate
      intracellular PA repertoire.

PMID- 9150420
TI  - Potent inhibition of human neuronal nitric oxide synthase by N(G)-nitro-L
      arginine methyl ester results from contaminating N(G)-nitro-L-arginine.
AB  - N(G)-Nitro-L-arginine methyl ester (L-NAME), inhibits the three isozymes of
      nitric oxide synthase (NOS) in vitro and in vivo. The mechanism of NOS inhibition
      by L-NAME is uncertain. L-NAME was a time-dependent inhibitor of neuronal NOS
      (nNOS). Concommitantly, L-NAME was hydrolyzed, non-enzymatically, to N(G)-Nitro-L
      arginine (L-NA) during the enzyme assay. The time-dependent inhibition of nNOS by
      L-NAME was the result of this time-dependent formation of L-NA. Furthermore, N(G)
      Nitro-L-arginine methyl amide, which is an isosteric analogue of L-NAME that is
      much less susceptible to hydrolysis, was a rapidly reversible weak inhibitor of
      NOS. These data suggested that L-NAME itself was a weak and rapidly reversible
      inhibitor of nNOS. Most of the inhibition of nNOS by a solution of L-NAME is the
      result of the formation of L-NA. L-NAME was a substrate for porcine liver
      esterase.

PMID- 9150421
TI  - An enzyme- linked immunosorbent assay for heparan sulfate proteoglycans.
AB  - An enzyme- linked immunosorbent assay (ELISA) for heparan sulfate proteoglycan
      (HSPG) was developed based on the high affinity binding profile of HSPG to
      lipoprotein lipase (LPL). LPL was shown to bind to precoated HSPG in dose
      dependent manner and was determined spectrophotometrically using specific anti-
      LPL antibody. This ELISA allowed to evaluate HSPG produced by PC12 cell with
      clear linearity at range of 10 - 500 ng/ml. Soluble chondroitin sulfate
      proteoglycan (CSPG) from rat brain, which was not detectable by this method, did
      not exhibit any inhibitory effects on affinity binding of HSPG to LPL, even if 8
      times higher concentrations of CSPG to HSPG was added. The sensitivity of this
      ELISA was about 100 times higher than that of conventional carbazole reaction
      method. These findings indicated its potential usefulness of this method for
      measuring small amounts of HSPG capable of binding to LPL and for studying
      biological implications of HSPG - LPL interaction.

PMID- 9150422
TI  - Antihyperglycemic mechanism of M16209, an antidiabetic agent, in 3T3-L1
      adipocytes.
AB  - We investigated the effect of M16209 (1-(3-bromobenzo[b]furan-2
      ylsulfonyl)hydantoin) on glucose transport and the insulin signaling system in
      mouse-derived 3T3-L1 adipocytes. When M16209 (30 and 100 microM) was added to 3T3
      L1 adipocytes and preincubated for 24 hours, the uptake of 2-deoxy-D-[3H]-glucose
      (2-DG) after insulin stimulation was enhanced. This effect was seen when
      preincubation with M16209 was performed in the presence of 6 and 20 ng/ml
      insulin, but M16209 did not increase the response to 600 ng/ml insulin. M16209
      (100 microM) did not interfere with (125)I-insulin binding or with tyrosine
      phosphorylation of the insulin receptor beta-subunit and IRS-1. M16209 (100
      microM) also had no effect on the level of glucose transporter (GLUT1 and GLUT4)
      protein, but it promoted the translocation of intracellular GLUT4 to the plasma
      membrane. In contrast, M16209 had no effect on the translocation of GLUT1. In
      summary, M16209 enhanced 2-DG uptake by 3T3-L1 adipocytes. Insulin binding to its
      receptor, autophosphorylation of the insulin receptor beta-subunit, and tyrosine
      phosphorylation of IRS-1 were unaffected by M16209. However, translocation of
      GLUT4 from the intracellular pool to the plasma membrane was facilitated.

PMID- 9150423
TI  - Antisense oligodeoxynucleotide to delta opioid receptors blocks cocaine-induced
      place preference in mice.
AB  - The effect of intracerebroventricular (i.c.v.) treatment with antisense
      oligodeoxynucleotide (A-oligo) to delta opioid receptor mRNA on cocaine-induced
      place preference was examined in mice. Cocaine (10 mg/kg, s.c.) produced a
      significant place preference. I.c.v. treatment with A-oligo (0.001-1
      microg/mouse) dose-dependently attenuated the cocaine (10 mg/kg, s.c.)-induced
      place preference, although mismatched oligodeoxynucleotide (1 microg/mouse,
      i.c.v.) was ineffective. In the present study, we found that the selective
      reduction in number and/or function of central delta opioid receptors by A-oligo
      suppresses the cocaine-induced place preference. These results suggest that the
      conditioned reward by cocaine may be partially mediated by central delta opioid
      receptors.

PMID- 9150424
TI  - Praziquantel has no direct effect on (Na(+)+K+)-ATPases and (Ca2(+)-Mg2+)ATPases
      of Schistosoma mansoni.
AB  - Therapeutic concentrations of praziquantel produce a rapid and intense
      contraction of the human flatworm Schistosoma mansoni. As an action on ATPases
      responsible for calcium homeostasis arises as a possible explanation for the
      molecular mechanism of this effect, we tested here the effect of praziquantel on
      different preparations from male adult worms that were previously characterized
      for their content in (Na(+)+K+)-ATPase and (Ca2(+)-Mg2+)ATPase activities from
      different origins. Concentrations as high as 100 microM praziquantel did not
      inhibit (Na(+)+K+)-ATPase from tegument and carcass nor (Ca2(+)-Mg2+)ATPase from
      heterogeneous (P1) and microsomal (P4) fractions. As 100 microM praziquantel was
      also without effect on calcium permeability of microsomal vesicles actively
      loaded with 45Ca2+, the present results discard three hypotheses recently raised
      for the mechanism of praziquantel-induced contraction of S. mansoni.

PMID- 9150425
TI  - Cloning of a human epididymis-specific mRNA, HE6, encoding a novel member of the
      seven transmembrane-domain receptor superfamily.
AB  - A novel gene product, HE6, showing homology to the seven transmembrane-domain
      (Tm7) receptor superfamily, has been cloned by differential screening from a
      human epididymal cDNA library. The cDNA clone represented an abundant
      approximately 5-kb mRNA, comprising 0.01% of the cDNA library. Northern blot
      analysis including various human tissues revealed an epididymis-specific
      expression. In situ transcript hybridization localized the mRNA within the
      epithelial cells lining the epididymal duct. Southern blot analysis, employing a
      fragment encoding part of the amino-terminal extracellular domain as a probe,
      identified an autosomal single-copy gene in the human genome. Homologous cDNA
      products showing 90% sequence identity were observed in the epididymides of all
      mammalian species investigated. A cloning and sequencing strategy, combining
      approximately 3.7-kb cDNA fragments obtained by conventional cDNA library
      construction with overlapping 5' rapid amplification of cDNA ends (RACE)
      fragments, yielded total sequence information of 4.7 kb for the human mRNA. This
      sequence comprises a long open reading frame of 3.1 kb. A homology search for
      related sequences revealed highest similarity (25% amino acid identity) with the
      secretin/vasoactive intestinal peptide (VIP) superfamily of G-protein-coupled
      receptors. The predicted extracellular amino-terminal extension, however, was
      much longer than in the other members, and showed similarity to highly
      glycosylated mucin-like cell-surface molecules.

PMID- 9150426
TI  - The manganese superoxide dismutase gene of Drosophila: structure, expression, and
      evidence for regulation by MAP kinase.
AB  - The gene encoding manganese superoxide dismutase (MnSOD) from Drosophila
      melanogaster has been isolated and its expression has been studied. In contrast
      to several mammalian MnSOD genes, the Drosophila gene contains a single intron
      and is transcribed into a single 0.8-kb transcript. Whole-mount in situ
      hybridization reveals extensive transcript accumulation in ovarian nurse cells
      and a heavy maternal contribution to the early embryo. Larval imaginal discs are
      enriched with MnSOD transcripts relative to other larval tissues, further
      suggesting a possible relationship between high MnSOD expression and mitotic
      activity. The 5'-upstream region contains several well-known regulatory elements
      including metal response, antioxidant response, and xenobiotic response elements
      (MRE, ARE, and XRE, respectively), sites for activator protein-1 (AP-1), nuclear
      factor-kappaB (NF-kappaB), adenosine 3',5'-cyclic monophosphate regulator binding
      element factor (CREB), as well as classic TATA and CAAT boxes. That MnSOD
      expression in Drosophila is regulated in part by the transcription factor AP-1
      via the MAP kinase signal transduction pathway is suggested by experiments which
      show that a hypomorphic mutation of the MAP kinase-encoding rolled gene
      substantially reduces levels of MnSOD transcripts and correlates with reduced
      resistance to oxidative stress in rolled mutants.

PMID- 9150427
TI  - The mouse elongation factor-2 gene: isolation and characterization of the
      promoter.
AB  - Elongation factor 2 (EF-2) is a protein involved in peptide chain elongation in
      eukaryotes. We isolated the mouse EF-2 gene and characterized its promoter. We
      showed that the majority of enhancer elements were located within 500 bp of the
      flanking sequence and identified a factor binding site sequence (CGTCACGTGACGC)
      located between nucleotides -58 and -47 containing two CGTCA motifs separated by
      two nucleotides. The motif represents a half-site for binding of the cAMP
      response element (CRE) binding protein (CREB). Mutation analysis indicated that
      the presence of one CGTCA site alone conferred cAMP inducibility, but the
      presence of one or two CGTCA sites and spacing nucleotides elicited cAMP
      independent, constitutive expression. UV cross-linking and DNA affinity
      chromatography revealed that three 40-, 43-, and 65-kD proteins bound to the CRE
      like element. Of these, the 65-kD protein was unique to the CRE-like element. The
      40-kD protein was ATF1 and the 43-kD protein with the molecular size of CREB was
      not CREB, on the basis of reactivity to their respective antibodies. Because ATF1
      responds poorly to cAMP induction, it is likely the contributor to the
      constitutive expression rather than inductive expression of the CRE-like element,
      and, thus, the EF-2 gene.

PMID- 9150428
TI  - Tissue-specific expression of pancreatic-type RNases and RNase inhibitor in
      humans.
AB  - The tissue-specific expression of five human pancreatic-type RNases and RNase
      inhibitor was analyzed by Northern hybridization against poly(A)+ RNA prepared
      from 16 normal tissues. The widespread expression of RNase 1 was observed in
      almost all of the tissues. RNase 4 and angiogenin showed a similar distribution
      of expression abundantly present in the liver. This suggested the identity of the
      cell types producing these two molecules. However, no relativity appeared to be
      present between the vascularization of the tissues and the angiogenin expression.
      A narrow range of expression of the eosinophil-derived neurotoxin gene was
      observed. This localization seems related to the phagocytic cells in the tissues.
      The undetectable level of the eosinophil cationic protein mRNA in normal tissues
      suggests that the differentiation of eosinophils, triggered by inflammation
      and/or atopy, is required. The expression of RNase inhibitor was found to be
      ubiquitous. The regulatory function of inhibitor against RNases in the cell
      should be considered in studying the physiological significance of the pancreatic
      type RNase family.

PMID- 9150429
TI  - Histone acetylation influences thyroid hormone and retinoic acid-mediated gene
      expression.
AB  - Thyroid hormone (T3) and retinoic acid (RA) receptors regulate transcription of
      the rat growth hormone (GH) gene through binding to a common hormone response
      element (HRE) in the promoter. We have investigated the effect of histone
      acetylation on hormone-dependent expression of the rat GH gene. We examined the
      effect of butyrate, which induces histone hyperacetylation, and trichostatin A
      (TSA), a highly specific inhibitor of histone deacetylases. GH-mRNA levels were
      significantly increased in pituitary GH4C1 cells incubated with T3 and RA, and
      this response was further stimulated in the presence of 1 mM butyrate. The effect
      of butyrate was mimicked by TSA. Butyrate and TSA also enhanced the activity of
      recombinant constructs containing the GH promoter directing chloramphenicol
      acetyl transferase (CAT) reporter gene expression. CAT activity increased by 4-
      to 8-fold after incubation with 1 nM T3 and 1 microM RA, and this response was
      stimulated 2- to 4-fold further in the presence of 0.25 mM butyrate. This
      concentration of butyrate did not influence basal expression of CAT. TSA produced
      a dose-dependent increase of CAT activity in the absence of ligands, and between
      5 and 200 nM potentiated the effect of T3 and RA. These compounds also increased
      the hormonal response of constructs in which the HRE was linked to heterologous
      [mouse mammary tumor virus (MMTV) and thymidine kinase (TK)] promoters. With
      butyrate >1 mM, basal activity of the GH promoter increased by more than 10-fold
      and the effect of T3 and RA was no longer observed. Overexpression of T3
      receptors was able to counteract the stimulation of basal CAT levels caused by
      butyrate. Thus, in the absence of ligand, the T3 receptor acts as a constitutive
      repressor of gene expression. Upon binding of the hormone, the T3 receptor is
      converted into an activator. Our findings suggest that histone acetylation, which
      alters chromatin structure, may play an important role in hormone-mediated
      transcriptional regulation.

PMID- 9150430
TI  - Subtractive cloning and characterization of DRAL, a novel LIM-domain protein down
      regulated in rhabdomyosarcoma.
AB  - A subtractive cloning procedure was used to characterize the molecular changes
      involved in transformation of normal myoblasts to rhabdomyosarcoma (RMS) cells.
      Here we describe the cloning of DRAL, a novel LIM-domain protein expressed in
      primary myoblasts but down-regulated in the RMS cell line RD. DRAL is a LIM-only
      protein with five LIM domains whereby one LIM domain consists only of the second
      half of the consensus motif. Interestingly, down-regulation of DRAL was not
      confined to the RD RMS cells, but was a phenomenon extended to other RMS cell
      lines of both embryonal and alveolar subtype, and to some breast cancer cell
      lines. Analysis of the expression pattern in normal human tissues revealed that
      DRAL is expressed at high levels in the heart, suggesting an important function
      in the specification of the terminally differentiated phenotype of heart muscle
      cells. Immunofluorescence studies using an antibody directed against recombinant
      DRAL localized the protein predominantly in the nucleus of cultured cells. On the
      basis of these results, we conclude that down-regulation of DRAL correlates with
      the tumor phenotype of RMS cells.

PMID- 9150431
TI  - Competitive-differential polymerase chain reaction for gene dosage estimation of
      erbB-1 (egfr), erbB-2, and erbB-3 oncogenes.
AB  - Increases in the average gene copy number (AGCN) of the erbB oncogenes,
      especially the erbB-2 gene, have been found in a variety of human cancers. Such
      information is useful with respect to prognosis of the disease. Poor
      reproducibility and DNA damage complicate quantitative polymerase chain reaction
      (PCR)-based methods. Therefore, we describe a quantitative PCR method for the
      estimation of AGCN in the oncogenes erbB-1 (egfr), erbB-2, and erbB-3. The method
      comprises a competitive and differential PCR in a one-tube reaction (competitive
      differential PCR, or cdPCR). Genomic sequences of the oncogene and the human beta
      globin (HBB) reference gene and two competitors for the oncogene and reference
      gene were amplified with two primer pairs simultaneously. The competitors were
      chosen to be amplified with the same efficiency as the genomic sequences. Using
      this method, we confirmed egfr and erbB-2 amplification in cancer cell lines and
      tumor tissue, and we also detected erbB-3 amplifications. Furthermore, gene
      dosage decreases were detectable, e.g., an erbB-2 hemizygosity in MCF-7 cells.
      Thus, cdPCR facilitates the detection of both increases and decreases in AGCN
      with high reproducibility, sensitivity, and accuracy. This method is therefore
      suitable for clinical studies on erbB oncogene dosage deviations.

PMID- 9150432
TI  - FMR1 enhancer is regulated by cAMP through a cAMP-responsive element.
AB  - FMR1 (Fra X Mental Retardation 1), a gene of unknown function, is responsible for
      an important hereditary mental retardation, the fragile X syndrome. In this
      study, a 22-bp enhancer (methylation sensitive element, MSE) in the FMR1 promoter
      was defined by DNase I footprinting assay, and the binding of this element by
      nuclear factor was prevented by DNA CpG methylation. A cAMP-responsive element
      (CRE)-like sequence and a myc-binding sequence in MSE were identified. In the
      transfection assay, MSE demonstrated a strong, methylation-sensitive enhancer
      activity. MSE could be bound by recombinant CRE-binding protein (CREB), and its
      activity was stimulated by CREB in a co-transfection assay. In PC12 cells,
      forskolin elevated MSE activity several fold, and this induction was abolished in
      CRE mutants. The involvement of cAMP in the expression of FMR1 should be a clue
      to both the function of FMR1 and the pathogenesis of fragile X syndrome.

PMID- 9150433
TI  - Expression of protein kinase regulator genes in human ear and cloning of a gamma
      subtype of the 14-3-3 family of proteins.
AB  - We have used oligonucleotides corresponding to conserved regions of protein
      kinase regulators of 14-3-3 gene family as primers to amplify these genes from
      cDNAs constructed from the human fetal inner ear. Sequence characterization of
      clones revealed that the 14-3-3 cDNA library from the fetal inner ear has high
      abundance of clones encoding a protein kinase regulator (theta subtype), a member
      of 14-3-3 gene family, and relatively lower abundance of clones for two other
      members of the gene family. One of these genes is identical to the eta subtype of
      human 14-3-3 genes; there is no cloned gene for the other subtype in the human 14
      3-3 gene family in the nucleic acid data bases. A sequence homology search
      revealed that the latter shared significant homology with the gamma subtype of
      the rat 14-3-3 family. On the basis of the sequence data, it appears that this
      clone represents a human homolog of the rat gamma subtype. The results
      demonstrate the expression of 14-3-3 genes in the inner ear, characterize a human
      homolog of the rat gamma subtype of 14-3-3, implicate these proteins in ear
      development, and indicate the utility of gene family polymerase chain reaction
      (PCR) for investigating gene expression in specific tissues.

PMID- 9150434
TI  - A four-amino-acid insertion in the ligand-binding domain inactivates hRXRbeta and
      renders dominant negative activity.
AB  - Retinoid X receptors (RXRs) are members of the steroid and thyroid hormone
      receptor superfamily of hormone-dependent transcription factors that mediate the
      pleiotropic effect of retinoids. Here, we report the initial characterization of
      an isoform of hRXR beta, termed hRXR beta3, which was previously identified as an
      H-2RIIBP isoform (Epplen and Epplen, 1992). The hRXR beta3 isoform cotains an in
      frame insertion of four amino acids (SLSR) in the ligand binding domain at codon
      419. The isoform is generated by alternate use of a 3' splice acceptor site and
      was detectable by reverse transcription polymerase chain reaction (RT-PCR) in all
      human tumor cell lines and mouse tissues examined. Chimeric receptors, in which
      the ligand-binding domain of hRXR alpha was substituted by the corresponding
      domain from hRXR beta3, were used to investigate the consequences of the SLSR
      insertion on the transactivation and DNA-binding functions of the chimeric
      receptor. Co-transfection assays revealed that a chimera RXR alpha/beta3 receptor
      failed to transactivate the RXR-specific CRBPII promoter, whereas the identical
      chimera lacking the SLSR insertion was active. The RXR alpha/beta3 receptor
      exhibited dominant negative activity against active retinoid X and retinoic acid
      receptors on retinoid-responsive promoters. Moreover, the RXR alpha/beta3 protein
      failed to interact physically with the retinoic acid receptor (RAR) to form
      heterodimers as detected by physical association assays, and failed to bind DNA
      containing an RAR-responsive element. Therefore, this suggests that the SLSR
      insertion in the ligand-binding domain of the RXR alpha/beta3 receptor is
      responsible for the altered behavior of the chimera. Our findings raise the
      possibility that RXR alpha/beta3, and perhaps hRXR beta3 isoform, function by
      titrating a limiting adaptor molecule that is involved in mediating retinoid
      function.

PMID- 9150435
TI  - Physical mapping of the murine casein locus reveals the gene order as alpha-beta
      gamma-epsilon-kappa.
AB  - The murine casein locus has been characterized by long-range restriction mapping
      and the analysis of large fragment genomic clones. Cloned sequences from five
      mouse casein genes (alpha, beta, gamma, epsilon, kappa) were used to screen a
      murine (strain 129) genomic library in a bacterial artificial chromosome vector
      (BAC). Of the nine clones isolated, two contained three casein genes alpha, beta,
      gamma and gamma, epsilon, kappa, respectively. The following combinations were
      found in other clones: alpha + beta, beta + gamma; and gamma + epsilon. Thus, the
      gene order in the locus can be deduced to be alpha-beta-gamma-epsilon-kappa. This
      order was confirmed by restriction analysis of the clones. A contig map of the
      clones and flanking sequences has been established by characterizing seven BAC
      clones, which together span approximately 470 kb. Long-range restriction analysis
      of genomic DNA indicates that the murine casein locus is confined to a 250-kb
      partial Xho I fragment. The alpha and beta casein genes were shown to be arranged
      in a tail-to-tail orientation.

PMID- 9150436
TI  - The promoter activity of the phospholipase C-gamma2 gene is regulated by a cell
      type-specific control element.
AB  - We have cloned and characterized a genomic DNA spanning the 5'-flanking region,
      the first and second exons, and the first intron of the human PLC-gamma2 gene.
      The proximal upstream region is highly GC-rich and lacks a TATA box, whereas the
      distal region contains several AT-rich tracts. Multiple transcription initiation
      sites were identified by primer extension analysis. Based on the transient
      transfection assays, the major transcriptional activation element was identified
      between -183 and +43 (G2SE) and a transcriptional repressive element was found
      between -303 and -184 (G2RE). The expression of PLC-gamma2 in various cell lines
      was examined using monoclonal anti-PLC-gamma2 antibody. PLC-gamma2 was highly
      expressed in B-cell lines such as Daudi, SP2, and Ramos cells, whereas it existed
      at very low levels in Jurkat, 3T3-L1, NBL-7, and C6Bu-1 cells. Moderate levels of
      PLC-gamma2 were also detected in C2C12, P19, U937, HL60, A431, and PC12 cells.
      The 4-kb genomic fragment upstream of -1,654 was able to activate transcription
      from the PLC-gamma2 promoter in Daudi and C2C12 cells, but not in Jurkat cells,
      which is consistent with the PLC-gamma2 protein expression levels in those cell
      lines. These results suggest that the cell-type-specific expression of PLC-gamma2
      might be attributed to the transcriptional regulation by the upstream cis
      element.

PMID- 9150437
TI  - Induction of O6-alkylguanine-DNA-alkyltransferase in the hepatocytes of rats
      following treatment with 2-acetylaminofluorene.
AB  - Molecular and immunohistological techniques have been used to study the induction
      in rat liver of the DNA repair protein O6-alkylguanine-DNA-alkyltransferase
      (ATase), following an acute dose (60 mg/kg) of the hepatocarcinogen, 2
      acetylaminofluorene (2-AAF). An increase in ATase activity was specific to the
      liver, with a five- to six-fold induction being observed 72 hr after
      administration of 2-AAF. A similar temporal increase of both activity and ATase
      protein (detected by immunoblotting) was observed up to 1 week following
      treatment, but after 2 weeks the activity had returned to control levels.
      Although maximal induction of hepatic ATase mRNA was observed as early as 24 hr,
      the levels remained elevated at least 1 week after 2-AAF treatment. Using a
      rabbit antiserum raised against purified recombinant rat ATase, ATase-specific
      staining was observed in the nuclei of both nonhepatocytes and hepatocytes in
      control liver sections. There was, however, a significant differential staining
      of hepatocytes across the liver lobule, with ATase staining being most intense in
      the periportal region. In the livers of 2-AAF-treated rats, an increased
      intensity of staining was observed in hepatocytes throughout the liver lobule,
      whereas the nonparenchymal cells showed much less, or no, increase in staining.
      The increased expression of ATase in hepatocytes and its differential
      distribution across the lobule were confirmed by image analysis. Thus, ATase
      induction in response to 2-AAF treatment was an hepatocyte-specific response and
      not confined to any particular region of the liver lobule.

PMID- 9150438
TI  - Protein quality--a determinant of the intracellular fate of membrane-bound
      cytochromes P450 in yeast.
AB  - To elucidate mechanisms determining the intracellular localization of cytochromes
      P450, authentic and mutant cytochromes P450 52A4 (P450Cm2) and P450 52A5
      (P450Alk2A) were heterologously expressed in Saccharomyces cerevisiae and the
      ultrastructure of the respective transformants was investigated by means of
      immunoelectron microscopy. As a result, overproduction of both wild-type P450
      forms resulted in a massive proliferation of tubular membrane structures
      distributed over the whole cytoplasm. In contrast, all mutant P450Cm2 and Alk2A
      forms tested were mainly localized within stacks of paired membranes which often
      occurred in close vicinity to the nucleus. As found by serial sectioning of a
      single cell, these stacked membranes bearing the mutant P450 actually represented
      plates of consecutive membranes arranged one upon the other. A tubular network of
      endoplasmic reticulum membranes as observed after expression of the wild-type
      proteins could not be detected. Generally, the kind of mutation introduced into
      the P450 forms did not influence the morphology of the induced membranes. Even
      single amino acid exchanges in the cytosolic domain caused the formation of
      membrane stacks. The common feature of all mutant P450 forms causing the
      formation of stacked membranes was, however, their lower protein stability after
      heterologous expression in the S. cerevisiae host cells, compared to the
      stability of the authentic cytochromes P450. Furthermore, the proliferated
      membranes containing the different P450 forms were characterized by means of
      subcellular fractionation experiments. Using this approach, clear differences in
      the distribution of spectrally active and inactive P450 molecules were found. The
      results obtained suggest the presence of an intracellular sorting mechanism based
      on the protein quality, which finally leads to the differences in the
      intracellular distribution of wild-type and mutant cytochromes P450.

PMID- 9150439
TI  - The human p167 gene encodes a unique structural protein that contains centrosomin
      A homology and associates with a multicomponent complex.
AB  - The characterization of novel cytoplasmic, structural, and enzymatic proteins has
      been enhanced by a panel of monoclonal antibodies specific for protein substrates
      of transforming and nontransforming c-Src mutants. These protein substrates have
      included the focal adhesion kinase (FAK), cortactin, AFAP-110, p120CAS, and
      p130CAS. The monoclonal antibody 4G8 was generated as part of this panel of
      antibodies and was used to isolate the human gene for a 167-kD polypeptide. The
      cDNA sequence is 5,238 nucleotides in length with a predicted open reading frame
      consisting of 1,382 amino acids. The polypeptide is largely hydrophilic and
      highly charged. The central region of p167 has 88% identity with the entire 278
      amino-acid encoded sequence of the murine centrosomin A gene. The carboxyl third
      of p167 contains a unique cluster of 10 amino acid repeats with the consensus
      sequence (A/M)DDDRGPRRG. The p167 protein was found primarily in the cytoplasm of
      lymphocytes and is part of a multicomponent protein complex with prominent
      members of 167, 120, 64, 45, 40, 38, and 25 kD. Finally, we illustrate the
      conservation of p167 and its associated complex, and demonstrate its expression
      in different human tissues and cell types. The data suggest that p167 is novel
      and has an important cellular function as a cytoplasmic structural protein.

PMID- 9150440
TI  - Syncope: current diagnosis and treatment.
AB  - The patient with syncope often poses a formidable diagnostic challenge. A large
      number of underlying causes must be considered, ranging in severity from benign
      to life-threatening. A careful, systematic clinical evaluation beginning with a
      history, physical examination, and ECG will establish the diagnosis in most
      patients, and the judicious use of specialized testing will confirm or uncover
      the cause in many of the remaining cases. Further basic and clinical research
      into the pathogenesis and treatment of neurocardiogenic syncope, the role of HUT
      testing in neurally mediated syncope, and the optimal use of EPS in patients with
      cardiac disease will markedly improve our management of these patients in the
      future.

PMID- 9150441
TI  - What doctors don't know about kidneys.

PMID- 9150442
TI  - The nature of renal cell injury.
AB  - The main functional change in patients with acute renal failure (ARF) is a
      decrease in glomerular filtration rate (GFR). The virtual complete recovery of
      renal function in those patients who survive ARF, as well as the minimal renal
      histological abnormalities during ARF when the GFR is less than 10 ml/min,
      suggest that a major component of the renal tubular cell injury is sublethal or
      reversible. Experimental models of acute tubular necrosis frequently have placed
      the emphasis on irreversible proximal tubular cell death. The nature of the renal
      tubular cell injury in ischemic acute renal failure, however, includes not only
      cell death (necrosis or apoptosis) but also sublethal injury causing cell
      dysfunction. The role of intracellular calcium, the calcium-dependent enzymes
      calpain, phospholipase A2 and nitric oxide synthase (NOS), in the
      pathophophysiology of this renal tubular cell injury during hypoxia/ischemia is
      described. The effects of calpain and nitric oxide (NO) on the cytoskeleton and
      cell adhesion are discussed. Potential mechanisms whereby tubular injury leads to
      a profound fall in GFR, including increased tubuloglomerular feedback and
      increased distal tubular obstruction, in ischemic acute renal failure are
      proposed.

PMID- 9150443
TI  - The importance of context in cytokine action.

PMID- 9150444
TI  - Biology of TGF-beta in knockout and transgenic mouse models.
AB  - This paper reviews the basic biology and biochemistry of the TGF-beta isoforms
      including their unique serine-threonine receptors and signaling intermediates.
      Dysregulation of TGF-beta expression and/or receptor/signaling function have been
      implicated in a wide variety of pathologies. We will discuss mechanisms
      underlying some of these disease processes as gained from study of transgenic
      mice in which expression of TGF-beta 1 has either been lost by targeted deletion
      of its gene, is overexpressed in a tissue-specific manner, or blocked by its
      latency associated peptide.

PMID- 9150445
TI  - Platelet-derived growth factor: a key regulator of connective tissue cells in
      embryogenesis and pathogenesis.
AB  - Studies of PDGF-A, PDGF-B and PDGF receptor-beta knock-out mice have revealed
      critical functions for the PDGF-PDGF receptor signaling systems in the ontogeny
      of connective tissue cells: the mesangial cells of kidney glomeruli and the
      alveolar smooth muscle cells (SMC) of the lung. The phenotypes of the PDGF mutant
      mice have also shed light on the identity and functions of these cell types, as
      well as revealed analogies suggesting that common morphogenetic principles have
      evolved for use in different organs, involving related growth factors and cell
      types. Although the lethality of PDGF knock-out mice has not allowed an
      investigation of the role of PDGF in SMC of the vessel wall, regulation of PDGF
      and its receptors in adult vessels following injury is consistent with a role for
      PDGF in the fibroproliferative response in the intima that occurs as part of the
      pathogenesis of atherosclerosis. PDGF modulation of connective tissue synthesis
      may thus be critical to connective tissue phenotype and proliferation in both
      embryogenesis and pathogenesis.

PMID- 9150446
TI  - Cytokine regulation of schistosome-induced granuloma and fibrosis.
AB  - Schistosomiasis mansoni, a major cause of hepatic fibrosis in many developing
      countries, triggers a granulomatous inflammatory reaction in response to its eggs
      that lodge in the liver. The egg antigens are eliminated slowly, and the
      persistent granulomatous response leads to prolonged matrix synthesis and hepatic
      fibrosis. In mice, soluble egg antigens (SEA) induce interleukin 4 synthesis,
      promoting a dominant T helper type 2 lymphocyte accumulation with the release of
      additional cytokines (IL-5, IL-10), which not only suppress Th1 lymphocyte subset
      cytokines, but mediate the characteristic pathophysiology. Manipulation of the
      cytokine profile with antagonists or exogenous cytokine delivery alters the
      course of the hepatic inflammation and fibrosis. In the evolution of the
      granulomatous response to the S. mansoni eggs, transforming growth factor beta
      (TGF-beta) is also produced that may modulate inflammation and regulate
      fibrogenesis. In TGF-beta 1-gene targeted mutant mice that over-express TGF-beta
      1 (TGF-beta 1 transgenics) or in which TGF-beta 1 has been inactivated (TGF-beta
      1-/-; null mutation) or partially inactivated (TGF-beta 1+/-; null mutation
      heterozygotes), the altered production of TGF-beta 1 impacts on S. mansoni
      granuloma and hepatic fibrosis. In addition to the Th1/Th2 cytokine balance,
      modulation of TGF-beta 1 may change the outcome of chronic inflammatory fibrotic
      disease.

PMID- 9150447
TI  - Latent transforming growth factor-beta: structural features and mechanisms of
      activation.
AB  - Transforming growth factor-beta are cytokines with a wide range of biological
      effects. They play a pathologic role in inflammatory and fibrosing diseases such
      as nephrosclerosis. TGF-beta s are secreted in a latent form due to noncovalent
      association with latency associated peptide (LAP), which is a homodimer formed
      from the propeptide region of TGF-beta. LAP is disulfide linked to another
      protein, latent TGF-beta binding protein (LTBP). LTBP has features in common with
      extracellular matrix proteins, and targets latent TGF-beta to the matrix.
      Activation of latent TGF-beta can be accomplished in vitro by denaturing
      treatments, plasmin digestion, ionizing radiation and interaction with
      thrombospondin. The mechanisms by which latent TGF-beta is activated
      physiologically are not well understood. Results to date suggest an important
      role for proteases, particularly plasmin, although other mechanisms probably
      exist. A general model of activation is proposed in which latent TGF-beta is
      released from the extracellular matrix by proteases, localized to cell surfaces,
      and activated by cell-associated plasmin.

PMID- 9150448
TI  - Regulation of vascular morphogenesis by the matricellular protein SPARC.

PMID- 9150449
TI  - TGF-beta in kidney fibrosis: a target for gene therapy.

PMID- 9150450
TI  - Gelatinase A is a glomerular mesangial cell growth and differentiation factor.
AB  - The members of the matrix metalloproteinase gene family play critical roles in
      numerous physiologic events, including cellular migration, tissue remodeling in
      wound healing and development, as well as in the evolution of the inflammatory
      process. The 72 kDa gelatinase A (formerly denoted 72 kDa Type IV collagenase) is
      centrally involved in the inflammatory and sclerotic events common to most forms
      of chronic glomerular disease. In this article recent studies are summarized
      which demonstrate that this particular enzyme can directly affect the
      proliferative and differentiation properties of the intrinsic glomerular
      mesangial cell, both in vitro and in vivo.

PMID- 9150451
TI  - TGF-beta and the endothelium during immune injury.
AB  - During immune injury, activation of endothelial cells by inflammatory cytokines
      stimulates leukocyte adhesion to the endothelium, turns the endothelium from an
      anticoagulant surface to one that is frankly procoagulant, and results in the
      release of vasoactive mediators and growth factors. Cytokine activation of
      endothelial cells also results in increased endothelial cell TGF-beta 1 synthesis
      and enhanced activation of latent TGF-beta, the latter involving a shift of
      plasmin production from the apical to subendothelial surface. In cytokine
      stimulated endothelial cells, TGF-beta hinders leukocyte adhesion and
      transmigration via inhibition of IL-8 and E-selectin expression. TGF-beta also
      profoundly diminishes cytokine-stimulated inducible nitric oxide synthase
      production and instead augments endothelial nitric oxide synthase expression.
      Thus, some of the TGF-beta actions on endothelium during immune activation can
      viewed as immunosuppressive. TGF-beta also influences mechanisms of vascular
      remodeling during the healing phase of immune injury. It stimulates PDGF-B
      synthesis by endothelial cells, causes bFGF release from subendothelial matrix,
      and promotes VEGF synthesis by non-endothelial cells. Together these mediators
      control angiogenesis, a critical component of the vascular repair phenomenon.
      Further, endothelial cell derived PDGF-B and bFGF influence the proliferation and
      migration of neighboring cells. Thus, endothelial cells and TGF-beta actions on
      the endothelium play important roles both during the initial phase of immune
      injury and during the later remodeling phase.

PMID- 9150452
TI  - Integrins as signaling molecules and targets for tumor therapy.
AB  - Adhesion molecules include ligands and receptors. Together they provide cells
      with anchorage and traction for migration, and the receptors also mediate signals
      that control cell polarity, survival, growth, differentiation and gene
      expression. Integrins are a major group of versatile adhesion receptors that
      serve both adhesive and signaling functions. They possess shared and unique
      specifics both outside and inside the cell. Many of the integrins share an
      affinity toward the RGD recognition sequence in their extracellular matrix
      ligands, but are still capable of distinguishing different RGD-containing
      proteins. The shared signaling pathways are likely to include changes in
      intracellular Ca2+ and PIP2 concentrations, and the activation of protein kinase
      C and focal adhesion kinase. Examples of integrin-specific signaling include that
      the alpha v beta 3 integrin (vitronectin receptor) can potentiate the effects of
      insulin and certain other growth factors and that the alpha 5 beta 1 integrin
      (fibronectin receptor) supports cell survival in serum-free cultures by up
      regulating the anti-apoptosis protein Bcl-2. Another integrin function is that
      some integrins, in particular alpha 5 beta 1, are necessary for fibronectin
      matrix formation. Overexpression of alpha 5 beta 1, which results in the assembly
      of additional fibronectin matrix, reduces tumorigenicity of cultured tumor cells.
      Systemic treatment of tumor-bearing mice with an artificially generated
      fibronectin matrix suppresses metastasis. These and other findings indicate that
      the ligand binding and signaling functions of integrins offer targets for new
      therapeutic approaches.

PMID- 9150453
TI  - Selectin ligands, leukocyte trafficking, and fucosyltransferase genes.

PMID- 9150454
TI  - The solid state environment orchestrates embryonic development and tissue
      remodeling.
AB  - Cell interactions with extracellular matrix and with other cells play critical
      roles in morphogenesis during development and in tissue homeostasis and
      remodeling throughout life. Extracellular matrix is information-rich, not only
      because it is comprised of multifunctional structural ligands for cell surface
      adhesion receptors, but also because it contains peptide signaling factors, and
      proteinases and their inhibitors. The functions of these groups of molecules are
      extensively interrelated. In this review, three primary cell culture models are
      described that focus on adhesion receptors and their roles in complex aspects of
      morphogenesis and remodeling: the regulation of proteinase expression by
      fibronectin and integrins in synovial fibroblasts; the regulation of osteoblast
      differentiation and survival by fibronectin, and the regulation of trophoblast
      differentiation and invasion by integrins, cadherins and immunoglobulin family
      adhesion receptors.

PMID- 9150455
TI  - Modulation of cell proliferation by the integrin cytoplasmic domain.
AB  - Integrin adhesion receptors modulate cell functions, including cell proliferation
      and survival. The beta 1C integrin, an alternatively spliced form of beta 1A,
      containing a unique cytoplasmic domain sequence, inhibits cell growth in vitro.
      In vivo, the expression of beta 1C correlates with a benign, nonproliferative
      phenotype in epithelial cells. The studies discussed in this article indicate
      that modulation of cell proliferation, in normal or pathological conditions,
      might be achieved by the regulated expression of variant integrin subunits.

PMID- 9150456
TI  - Integrins and laminins in tissue remodeling.

PMID- 9150457
TI  - Adhesion molecules in the glomerular mesangium.
AB  - Experimental evidence indicates that extensive "cross-talk" exists between
      glomerular cells, extracellular matrix molecules and soluble mediator substances
      affecting the proliferative and secretory phenotype of glomerular mesangial
      cells. Both matrix and cytokines regulate mesangial cell behavior in vitro and in
      vivo after binding to specific cell surface receptors. It appears as if the
      concerted action of insoluble and soluble ligands on mesangial cells involves a
      reciprocal regulation of matrix molecules and cytokines as well as expression and
      affinity of their respective receptors. Elucidation of the potential biologic and
      clinical relevance of cell-matrix interactions in the glomerular mesangium
      represents a challenging goal in current kidney research. This brief review
      summarizes recent investigations concerning regulation of expression and function
      of adhesion molecules and matrix receptors in the mesangium. In addition to
      results from cell culture studies, descriptive findings on expression and
      regulation of adhesion molecules and their potential role for altered mesangial
      cell behavior in glomerular disease is considered.

PMID- 9150459
TI  - Leukocytes, cell adhesion molecules and ischemic acute renal failure.
AB  - Ischemic acute renal failure (ARF) is a common clinical syndrome, associated with
      high morbidity and mortality, for which there is no specific therapy.
      Polymorphonuclear neutrophils (PMN) recruited during reperfusion have been
      implicated as mediators of renal parenchymal injury in ischemic ARF. Leukocyte
      adhesion molecules appear to facilitate PMN recruitment in this setting.
      Complementary studies using monoclonal antibodies, antisense oligonucleotides and
      gene "knock-out" indicate that blockade of CD11/CD18 integrins and intercellular
      adhesion molecule-1 (ICAM-1) attenuates ARF in some experimental models of renal
      ischemia. These exciting observations may herald the development of novel anti
      adhesion strategies for use in human disease.

PMID- 9150458
TI  - Emerging paradigms of integrin ligand binding and activation.
AB  - Adhesion of cells to each other or to the extracellular matrix provides essential
      signals that regulate many cellular functions including cell migration,
      proliferation, differentiation and apoptosis. The integrin superfamily
      orchestrates many of these complex adhesive events through regulated interactions
      with a large variety of ligands. Crystallization of some ligands and of a ligand
      binding integrin domain, reviewed here, together with extensive mutagenesis
      studies are beginning to shed light on the inner workings of these receptors.

PMID- 9150460
TI  - Leukocyte migration in immune complex glomerulonephritis: role of adhesion
      receptors.
AB  - The application of our evolving knowledge of adhesion receptors to experimental
      models of immune complex glomerulonephritis has led to substantial advances in
      our understanding of how leukocytes emigrate from the vasculature into glomeruli
      and produce glomerular dysfunction. With respect to neutrophil (PMN) migration
      and activation in the context of nephritis, the adhesion molecules alpha M beta
      2, alpha IIb beta 3, and intercellular adhesion molecule-1 (ICAM-1) seem to be
      most essential, with more modest (and less well defined) contributions by P
      selectin, alpha 4 beta 1, and vascular cell adhesion molecule-1 (VCAM-1). The
      influx of PMNs is driven largely by complement and alpha chemokines. In contrast
      to PMNs, monocyte/macrophage migration and activation during nephritis appear to
      be largely mediated by the adhesion molecules alpha L beta 2, alpha 4 beta 1,
      ICAM-1, VCAM-1, and potentially P-selectin. Monocyte/macrophage migration also
      differs from that of PMNs in that it is complement-independent and involves beta
      chemokines. Further refinement of our understanding of the role of adhesion
      receptors in immune glomerulonephritis may eventually lead to clinically
      applicable strategies to ameliorate glomerular inflammation and resulting
      glomerulosclerosis.

PMID- 9150461
TI  - Adhesion molecules and rejection of renal allografts.
AB  - Despite an increasing amount of immunohistochemical and molecular biology data
      relating to the pathogenesis of kidney transplant rejection, the pathological
      diagnosis of this condition still rests on routine light microscopy. The
      detection of changes in expression and distribution of adhesion molecules in
      renal allograft biopsies may open a new era of increased accuracy of rejection
      diagnosis. Of the various adhesion molecule reactivities, peritubular capillary
      VCAM-1 staining appears to be the most specific finding for chronic rejection.
      This same staining reaction is seen in acute rejection, but may have less
      specificity in that setting.

PMID- 9150462
TI  - Angiotensin II and L-arginine in tissue fibrosis: more than blood pressure.
AB  - Angiotensin II (Ang II) blockade and restriction of dietary protein are thought
      to retard progression of renal disease primarily by reducing glomerular capillary
      pressure and thereby reducing injury to renal tissues. Relatively recent data
      suggest that both of these therapies may also act through pressure-independent
      mechanisms to reduce repair processes that follow tissue injury and which, if not
      self-limited, can continue to cause tissue fibrosis and organ failure. We review
      recent data suggesting that Ang II is a profibrotic molecule independent of blood
      pressure. Therapeutic actions of dietary restriction of total protein and
      restriction of the amino acid L-arginine that appear independent of pressure are
      also discussed. These effects are separated into those that reduce injury and
      those that reduce tissue repair. Finally, we ask whether the Ang II blockade or
      restriction of dietary protein could be more effective if they were aimed not
      only at limiting injury, but also at halting excessive repair.

PMID- 9150464
TI  - Can Alport syndrome be treated by gene therapy?

PMID- 9150463
TI  - Therapeutic potential of RGD peptides in acute renal injury.

PMID- 9150465
TI  - Cyclic ADP-ribose metabolism in rat kidney: high capacity for synthesis in
      glomeruli.
AB  - Recent discovery of cyclic ADP-ribose (cADPR) as an agent that triggers Ca2+
      release from intracellular stores, through ryanodine receptor channel, is an
      important new development in the investigation of intracellular signaling
      mechanisms. We determined the capacity of kidney and its components for synthesis
      of cADPR from beta-NAD, that is catalyzed by enzyme ADP-ribosyl cyclase, and
      enzymatic inactivation that is catalyzed by cADPR-glycohydrolase. Little or no
      activity of ADP-ribosyl cyclase was found in extracts from the whole rat kidney,
      renal cortex, outer and inner medulla. On the other hand, incubation of beta-NAD
      with similar extracts from rat liver, spleen, heart, and brain resulted in
      biosynthesis of cADPR. In addition, extracts from suspension of proximal tubules
      or microdissected proximal convoluted tubules virtually lacked ADP-ribosyl
      cyclase activity. In sharp contrast to proximal tubules and cortex, extracts from
      glomeruli had high ADP-ribosyl cyclase activity, similar to that found in non
      renal tissues. Authenticity of cADPR biosynthesized in glomeruli was documented
      by several criteria such as HPLC analysis, effect of inhibitors and homologous
      desensitization of Ca(2+)-release bioassay. On the other hand, the activity of
      cADPR-glycohydrolase was similar in extracts from glomeruli and in extracts from
      kidney cortex. Mesangial cells and vascular smooth muscle cells grown in primary
      culture displayed considerable ADPR-ribose cyclase activity. Our results show
      that extracts from glomeruli, unlike extracts from renal tissue zones and
      proximal tubules, have a singularly high capacity for synthesis of cADPR. We
      surmise that cADPR-triggered Ca(2+)-releasing system can serve as an
      intracellular signaling pathway that may be operant in regulations of glomerular
      cell functions.

PMID- 9150466
TI  - Effects of insulin on rat renal microvessels: studies in the isolated perfused
      hydronephrotic kidney.
AB  - Although insulin is demonstrated to decrease vascular tone, the role of insulin
      in renal microcirculation has not been fully determined. In the present study,
      the effect of insulin on renal microvascular tone was assessed using the isolated
      perfused hydronephrotic rat kidney. Insulin (300 microU/ml) had no effect on the
      basal renal microvessel diameter. In addition, insulin did not alter myogenic
      (that is, pressure-induced) constriction of preglomerular microvessels, with
      similar magnitude of constriction of preglomerular microvessels, with similar
      magnitude of constriction observed in response to elevated renal perfusion
      pressure from 80 to 180 mm Hg (interlobular artery, -23 +/- 3% vs. -19 +/- 4%;
      afferent arteriole, -22 +/- 3% vs. -21 +/- 4%, for control and insulin,
      respectively). In striking contrast, insulin dose-dependently reversed the
      norepinephrine (NE)-induced tone of interlobular arteries, afferent arterioles,
      and efferent arterioles, with 94 +/- 9%, 104 +/- 6%, and 86 +/- 10% reversal at
      300 microU/ml, respectively. These vasodilator actions were markedly inhibited by
      N-Arg; in the presence of N-Arg, insulin (300 microU/ml) exerted only a modest
      dilator action on interlobular arteries (24 +/- 9% reversal), afferent arterioles
      (23 +/- 10% reversal), and efferent arterioles (14 +/- 9% reversal). A similar
      renal microvascular responsiveness to insulin was also observed during
      angiotensin II (Ang II)-induced constriction. In conclusion, the ability of
      insulin to dilate the renal microvasculature differs, with marked inhibitory
      action during NE/Ang II-induced constriction and almost no inhibition during
      myogenic constriction. Furthermore, the present study suggests that the insulin
      induced renal vasodilation is mediated by nitric oxide.

PMID- 9150467
TI  - Interaction between beta 2-microglobulin and advanced glycation end products in
      the development of dialysis related-amyloidosis.
AB  - Dialysis related amyloidosis (DRA) is a progressive debilitating complication of
      long-term dialysis. beta 2-microglobulin (beta 2m) amyloid deposition occurs
      preferentially in older patients and initially is located in collagen-rich osteo
      articular tissues. Since an age-dependent increase in the formation of advanced
      glycation end products (AGE) has been observed in collagen-containing structures,
      we hypothesized that AGE-modified beta 2m in the amyloid of DRA may be formed
      locally in osteo-articular structures as a subsequent event of its binding to
      collagen-AGE. Based on this hypothesis, we investigated the binding between beta
      2m and AGE-modified collagen (collagen-AGE) in vitro. Significantly larger
      amounts of human beta 2m were bound to types I to IV of immobilized collagen-AGE
      than to unmodified collagens (P < 0.0001). The quantity of beta 2m bound to
      collagen-AGE was dependent on the concentrations of both beta 2m and of AGE
      contained in collagen (P < 0.01). Unmodified beta 2m was more avidly bound to
      collagen-AGE or collagen in comparison to AGE-modified beta 2m (P < 0.0001). beta
      2m bound to collagen-AGE could be modified further by nonenzymatic glycosylation
      during three weeks of incubation with physiologic concentrations of glucose.
      Similar processes in vivo may be important in the pathobiology of DRA.

PMID- 9150468
TI  - Contrasting effects of proinflammatory and T-helper lymphocyte subset-2 cytokines
      on the 5-lipoxygenase pathway in monocytes.
AB  - Human peripheral blood monocytes (HPBMs) express 5-lipoxygenase (5-LO) and 5-LO
      activating protein (FLAP), and hence have an ability to synthesize
      proinflammatory leukotrienes (LTs). Regulation of 5-LO and FLAP expression is a
      major determinant of cellular LT synthesis. We examined the effects of
      proinflammatory [interleukin (IL)-1 and interferon (IFN)-gamma] and T helper
      lymphocyte subset 2 (TH-2; IL-4 and IL-13) cytokines on (1) LTB4 production, and
      (2) 5-LO and FLAP expression in HPBMs. We show that IL-1 and IFN-gamma stimulate,
      whereas IL-4 and IL-13 inhibit ionophore-activated LTB4 release. The stimulatory
      effects of IL-1 and IFN-gamma were apparent at 16 to 36 hours of incubation. IL-1
      modestly increased FLAP mRNA and significantly increased 5-LO mRNA steady state
      levels at 24 and 36 hours of incubation, respectively. IFN-gamma did not change
      the mRNA or protein expression of either 5-LO or FLAP. The inhibitory effects of
      IL-4 and IL-13 were associated with decreased FLAP mRNA and protein steady state
      levels. These results demonstrate that regulation of monocyte LTB4 biosynthesis
      by different cytokines proceeds via different pathways that partly involve
      modulation of the expression of the key proteins, 5-LO and FLAP. In addition, the
      contrasting effects of proinflammatory and TH-2-derived cytokines on monocyte
      LTB4 production demonstrate mechanisms by which cytokine subpopulations may
      modulate monocyte function in inflammation.

PMID- 9150469
TI  - Effects of chloride channel blockers on hypoxic injury in rat proximal tubules.
AB  - These studies examined the pathways and consequences of chloride uptake into
      proximal tubule cells during in vitro hypoxia. The chloride channel blocker
      diphenylamine-2-carboxylate (DPC) markedly reduced the degree of hypoxia-induced
      membrane damage as measured by the release of lactate dehydrogenase (LDH). DPC
      reduced the release of LDH from hypoxic tubules from 38 +/- 2.7% to 16 +/- 1.7%
      after 30 minutes of hypoxia (P < 0.001, N = 16) and also reduced 36Cl- uptake by
      hypoxic tubules. The reduction in LDH release was not associated with better
      preservation of cell ATP content or with protection against hypoxia-induced DNA
      damage. Other Cl- channel blockers, such as niflumic acid, 5-nitro-2-(3
      phenylpropylamino)-benzoate (NPPB) and 2-[(2-cyclopentyl-6,7-dichloro-2,3-dihyrdo
      2-methyl-1-oxo-1H-in den-5-yl)oxy] acetic acid (IAA-94) provided even greater
      protection than DPC and were as effective as 2 mM glycine. The Cl- channel
      blockers appear to act late in the course of hypoxic injury since DNA damage, an
      early manifestation of injury, is not prevented by the blockers and since
      addition of the Cl- channel blocker after the hypoxic injury has begun reduces
      further membrane damage. These results support the conclusion that transport
      through Cl- channels contributes to hypoxic cell injury in proximal tubular
      cells.

PMID- 9150470
TI  - Effects of sex hormones on fluid and solute transport in Madin-Darby canine
      kidney cells.
AB  - Polycystic kidney disease progresses more rapidly in men than in women. To
      investigate the basis for this sexual dimorphism, we exposed Madin-Darby canine
      kidney (MDCK) cells grown on collagen-coated cell culture inserts to control
      media, or to estradiol or testosterone (1 nM-1 microM). Compared to control and
      estradiol-treated cells, testosterone stimulated fluid secretion in a dose
      dependent manner, enhancing fluid secretion 4.8-fold at 1 nM and 19.7-fold at 1
      microM (0.59 +/- 0.18 vs. 0.03 +/- 0.01 microliter/cm2/hr, P < 0.001). Chloride
      transport paralleled fluid secretion. Testosterone increased cellular cyclic AMP
      levels 3.2-fold at 1 nM and 12.3-fold at 1 microM (81.3 +/- 30.7 vs. 6.6 +/- 3.3
      pmol/mg protein, P < 0.001). GDP beta S (500 microM), an inhibitor of Gs, and
      2',3'-dideoxyadenosine (10 microM), an inhibitor of the catalytic subunit of
      adenylate cyclase, suppressed testosterone-induced fluid and solute secretion.
      Neither testosterone nor estradiol had any effect on microsomal Na,K-ATPase
      activity, cellular proliferation or cellular total protein content. Our studies
      show that testosterone stimulates fluid secretion and solute transport by MDCK
      cells by increasing cAMP generation. In vivo, testosterone may contribute to cyst
      expansion by enhancing fluid secretion. This observation may help explain the
      worse prognosis of polycystic kidney disease observed in men.

PMID- 9150471
TI  - Defective renal calcium reabsorption in genetic hypercalciuric rats.
AB  - Idiopathic hypercalciuria is a frequent cause of calcium (Ca) containing kidney
      stones. We have previously shown that there is increased intestinal Ca absorption
      in selectively inbred genetic hypercalciuric stone forming (GHS) rats; however,
      excess Ca excretion persists when the rats are fed a low Ca diet indicating a
      defect in renal Ca reabsorption and/or increased bone resorption. To determine if
      GHS rats have a defect in renal Ca reabsorption we performed 14C-inulin clearance
      studies on parathyroidectomized female GHS and control (Ctl) rats. After three
      baseline collections, chlorothiazide (CTZ) or furosemide (FUR) was infused and
      three more collections were obtained. Both GFR and filtered load of Ca did not
      differ among the groups; however, fractional and absolute excretion (UcaV) of Ca
      was three times higher in GHS rats. The increased Ca excretion was not diminished
      by a low Ca diet. Urine flow rate nearly tripled in all rats after either FUR or
      CTZ. After CTZ, UcaV was decreased to a greater extent in GHS compared to Ctl
      rats. After FUR, UcaV was increased to a greater extent in Ctl rats compared to
      GHS rats. These data indicate that GHS rats have a defect in renal Ca
      reabsorption, in addition to increased intestinal Ca absorption. The effect of
      CTZ was greater, and that of FUR was smaller, in GHS compared with Ctl rats,
      suggesting that the defect in renal Ca handling might be at the level of the
      thick ascending limb.

PMID- 9150472
TI  - Distribution of alpha 1B-adrenergic receptor mRNA expression along rat nephron
      segments.
AB  - Although several alpha-adrenergic receptor genes are expressed in the rat kidney,
      little information is available on their expression in the renal nephron
      segments. We investigated the distribution of alpha 1B-adrenergic receptor mRNA
      in rat nephron segments using reverse transcription and polymerase chain reaction
      (RT-PCR). The nephron segments of six- to eight-week-old male Sprague-Dawley rats
      were microdissected. Total RNA was prepared by the acid-guanidinium-phenol
      chloroform method and used in the following RT-PCR assay. The PCR products were
      size-fractionated with electrophoresis, visualized with ethidium bromide staining
      and confirmed by Southern blot analysis. Because the PCR primers spanned an
      intron, the amplification product of the predicted size was considered to be from
      alpha 1B-adrenergic receptor cDNA and not from genomic DNA. The PCR products were
      detected in glomerulus (Glm), proximal convoluted and straight tubules (PCT, PST)
      and cortical and medullary thick ascending limbs of Henle (CTAL, MTAL). No
      signals were detected in cortical or medullary collecting ducts (CCD, MCD). Large
      signals were detected in the PCT, and PST, while small signals were found in the
      Glm, CTAL and MTAL. The alpha 1B-adrenergic receptor mRNA was detected for the
      first time in rat Glm, PCT, PST and TAL using RT-PCR. alpha 1BAR mRNA seems to be
      expressed in the specific sites along the nephron and may play significant roles
      in renal functions, although the specific physiological effects of the renal
      alpha 1B-adrenergic receptor are unknown.

PMID- 9150473
TI  - Transforming growth factor beta 1 and renal injury following subtotal nephrectomy
      in the rat: role of the renin-angiotensin system.
AB  - Transforming growth factor-beta (TGF-beta) and the renin-angiotensin system (RAS)
      have both been implicated in the pathogenesis of chronic renal disease. The
      present experiment investigated the chronology of TGF-beta 1 gene expression
      following subtotal nephrectomy (STNx) in the rat and the effect of blocking the
      RAS by angiotensin converting enzyme (ACE) inhibition or by angiotensin II
      receptor (AT1) antagonism. Rats that had undergone subtotal nephrectomy developed
      hypertension, proteinuria, renal impairement, glomerulosclerosis,
      tubulointerstitial fibrosis and mononuclear cell infiltration. These changes were
      associated with a 2.5-fold increase in TGF-beta 1 gene expression during a 16
      week time course. In situ hybridization localized TGF-beta 1 mRNA to sclerotic
      glomeruli, areas of tubuloin-terstitial injury and sites of mononuclear cell
      infiltration. Administration of the ACE inhibitor ramipril and the AT1 receptor
      blocker valsartan blunted the increase in TGF-beta 1 mRNA, and attenuated the
      structural and functional manifestations of injury. These data suggest an
      interaction between the intrarenal RAS and TGF-beta in the pathogenesis of the
      glomerular and tubulointerstitial fibrosis that follow a major reduction in renal
      mass.

PMID- 9150474
TI  - Renal TGF-beta in HIV-associated kidney diseases.
AB  - Human immunodeficiency virus (HIV)-1 infection may be complicated by progressive
      renal glomerular disease, including focal segmental glomerulosclerosis (FSGS) and
      proliferative glomerulonephritis. We examined renal tissue from 71 patients,
      including biopsies and autopsies from patients in the presence and absence of HIV
      1 infection. We assessed the extent of TGF-beta, interstitial fibrosis, and
      interstitial CD45-positive cellular infiltrate using immunohistochemistry.
      Extracellular TGF-beta 1/beta 3 was largely confined to the renal interstitium,
      with the highest scores in HIV-seropositive renal disease and crescentic
      nephritis. Among all biopsies, the TGF-beta 1/beta 3 score correlated with the
      fibrosis score (r = 0.79, P < 0.0001) and with the CD45 score (r = 0.60, P <
      0.0001). Biopsies from HIV-infected patients, taken together, showed marginally
      more TGF-beta 1/beta 3 compared to biopsies from HIV-uninfected patients (P =
      0.05); similarly, HIV-associated FSGS showed marginally more TGF-beta 1/beta 3
      compared to FSGS biopsies obtained from HIV-uninfected patients (P = 0.05).
      Intracellular TGF-beta 1 and TGF-beta 3 were both expressed by renal tubular
      epithelial cells and in extraglomerular crescents, whereas TGF-beta 3 was also
      present within interstitial mononuclear cells and eosinophils, and, exclusively
      in HIV-infected patients, within glomerular cells. In conclusion, TGF-beta
      expression was increased in several progressive glomerular diseases, and was
      particularly but not uniquely elevated in HIV-associated renal diseases.

PMID- 9150475
TI  - Development of a population-specific regression equation to estimate total body
      water in hemodialysis patients.
AB  - We have previously shown that the impedance index (height corrected resistance)
      is a valid and reliable correlate of total body water (TBW) in hemodialysis
      patients. We estimated TBW by single frequency bioelectrical impedance analysis
      (BIA) in 3009 in-center hemodialysis patients, and developed an ESRD-specific TBW
      equation from routinely available demographic and anthropometric variables. The
      mean +/- SD age was 60.5 +/- 15.5 years; 47% were female, 47% African-American,
      and 36% diabetic. Dialysis duration was 3.8 +/- 3.7 years. Mean TBW was 40.8 +/-
      9.3 kg, 56 +/- 9% of body weight. A stepwise linear regression equation was fit
      on a two-thirds random sample, deriving significant parameter estimates for the
      variables age, gender, height, weight, diabetic status, weight squared, and the
      cross-products of age and gender, age and weight, gender and weight, and height
      and weight. The equation was then validated in the remaining one-third sample,
      and compared with TBW estimates by the Watson and Hume-Weyer formulae. TBW
      estimated by our equation (40.6 +/- 8.6 kg) was not significantly different from
      the BIA TBW (40.5 +/- 9.3 kg). In contrast, TBW estimated by the Watson (37.0 +/-
      7.6 kg) and Hume-Weyer (37.9 +/- 7.7 kg) formulae underestimated TBW by a mean of
      3.5 and 2.6 kg, respectively. A population-specific equation provides superior
      prediction of TBW in hemodialysis patients. The use of formulae developed and
      validated in non-uremic populations may result in underestimates of TBW in
      patients with ESRD, and potentially, overestimates of dialysis dose approximated
      by the clearance-time to TBW ratio (Kt/V).

PMID- 9150476
TI  - Mycophenolate mofetil limits renal damage and prolongs life in murine lupus
      autoimmune disease.
AB  - Classical immunosuppressants like cyclophosphamide give excellent results in
      human lupus nephritis. However, they augment malignancies and viral infections.
      Here we investigated the effect of the new immunosuppressant agent, mycophenolate
      mofetil (MMF), in New Zealand Black x New Zealand White (NZBxW) F1 hybrid mice, a
      model of genetically determined immune complex disease that mimics systemic lupus
      in humans. MMF has a selective antiproliferative effect on T- and B-lymphocytes,
      inhibits antibody formation and blocks the glycosylation of lymphocyte
      glycoproteins involved in the adhesion of leukocytes to endothelial cells. Two
      groups of NZBxW mice were used: group 1 (N = 20) given daily MMF (60 mg/kg p.o.)
      and group 2 (N = 15) given daily vehicle alone. Treatment started at three months
      of age and lasted until the death of the animals. Results showed that percentage
      of proteinuric mice was significantly reduced by MMF treatment and serum BUN
      levels were also lower than vehicle. MMF had a suppressive effect on autoantibody
      production and protected animals from leukopenia and anemia. Life survival of MMF
      treated lupus mice was significantly improved in respect to untreated animals.
      Thus, MMF delayed renal function deterioration and prolonged life survival in
      murine lupus nephritis. MMF has been already recognized as reasonably well
      tolerated in renal transplant patients and despite its gastrointestinal toxicity
      its overall safety profile appears superior to azathioprine. Human studies are
      needed to establish whether MMF may function as a steroid-sparing drug in lupus
      nephritis.

PMID- 9150477
TI  - Suppressive effect of calcium on parathyroid hormone release in adynamic renal
      osteodystrophy and secondary hyperparathyroidism.
AB  - Serum parathyroid hormone (PTH) levels are markedly lower in patients with the
      adynamic lesion (AD) of renal osteodystrophy than in those with secondary
      hyperparathyroidism (2 degrees HPT), but serum PTH values are often moderately
      elevated in AD when compared to subjects with normal renal and parathyroid gland
      function (NL). To study the inhibitory effect of calcium on PTH release in AD and
      in 2 degrees HPT, the response to two-hour intravenous calcium infusions was
      examined in 6 patients with AD, in 31 patients with 2 degrees HPT and in 20 NL.
      Basal serum PTH levels were 88 +/- 51, 536 +/- 395, and 26 +/- 6 pg/ml,
      respectively, in AD, 2 degrees HPT and NL, whereas basal ionized calcium levels
      did not differ. When expressed as a percentage of pre-infusion values, PTH levels
      at the end of two-hour calcium infusions were higher both in AD (23.2 +/- 5.6%)
      and in 2 degrees HPT (27.8 +/- 12.3%) than in NL, (11.9 +/- 5.8%, P < 0.001).
      Both the amplitude of suppression (%) and the rate of decline (min-1) in serum
      PTH were less in AD and 2 degrees HPT than in NL, P < 0.05 for each parameter;
      corresponding values for each group, with 95% confidence intervals, were 77% (73
      to 82) and 0.039 min-1 (0.030 to 0.048) in AD, 72% (68 to 76) and 0.031 min-1
      (0.025 to 0.036) in 2 degrees HPT and 87% (84 to 89) and 0.070 min-1 (0.058 to
      0.089) in NL. Neither variable differed between AD and 2 degrees HPT. Basal and
      nadir serum PTH levels were highly correlated: r = 0.95 and P < 0.05 in AD; r =
      0.90 and P < 0.01 in 2 degrees HPT; r = 0.75 and P < 0.01 in NL. The slope of
      this relationship was less, however, both in AD and in 2 degrees HPT than in NL,
      P < 0.05 by analysis of co-variance. Thus, serum PTH levels fell below 20% of pre
      infusion values in fewer subjects with AD (1 of 6) or 2 degrees HPT (9 of 31)
      than in NL (17 of 20) (chi 2 = 17.81, P < 0.005). The results indicate that the
      inhibitory effect of calcium on PTH release in vivo does not differ in AD and 2
      degrees HPT despite marked differences in basal serum PTH levels. Variations in
      functional parathyroid gland mass rather than disturbances in calcium-sensing by
      the parathyroids probably account not only for the lower basal serum PTH levels
      in patients with AD compared to those with 2 degrees HPT, but also for the
      moderately elevated serum PTH values commonly seen in patients with AD.

PMID- 9150478
TI  - Thin GBM nephropathy: premature glomerular obsolescence is associated with
      hypertension and late onset renal failure.
AB  - Thin glomerular basement membrane (GBM) nephropathy, also called familial benign
      hematuria, is characterized by chronic hematuria and uniform thinning of the
      lamina densa of the glomerular basement membrane. It generally holds an excellent
      renal prognosis. Alport syndrome in early stages can also show attenuation of the
      GBM; conversely, renal insufficiency has been reported in familial benign
      hematuria. To discern early Alport syndrome from thin GBM nephropathy, we carried
      out a prospective epidemiological study in which 19 normotensive and non-azotemic
      adult patients with chronic microscopic (18 of 19) and macroscopic (1 of 19)
      hematuria and biopsy-proven thin GBM nephropathy were followed for a median of 12
      years (range 9 to 15 years). Renal biopsies of thin GBM patients at entry showed
      an increased incidence of focal global glomerulosclerosis when compared to
      disease controls as IgA nephropathy (P = 0.047) and normal renal tissue (P =
      0.0075). All renal biopsies showed the presence of the Goodpasture antigen when
      tested immunohistochemically. Presence of Alport syndrome was excluded clinically
      as none of the patients had complaints of hearing loss or abnormalities by
      audiography and ophthalmology. At the end of follow-up, the incidence of
      hypertension in thin GBM nephropathy (35%) exceeded that of healthy clinical
      controls (P = 0.048), and one hypertensive patient developed mild renal failure.
      In the normotensive patients, the glomerular filtration rate at follow-up as
      measured by inulin clearance was reduced in three out of seven; these were over
      50 years of age. Although no family members were known to have renal disease at
      inclusion, within four families six elderly first degree relatives had developed
      unexplained renal insufficiency at the end of follow-up. Thus, thin GBM
      nephropathy predisposes to premature glomerular obsolescence, leading in time to
      increased incidences of hypertension and late onset renal insufficiency.

PMID- 9150479
TI  - Nephropathy of type II diabetes: evidence for hereditary factors?
AB  - Family studies point to an important genetic element in the genesis of diabetic
      nephropathy, but it is not known whether renal abnormalities are present prior to
      the onset of diabetes. To address this issue we examined all consecutive patients
      suffering from type II diabetes with a duration of more than 10 years who
      attended a diabetes outpatient clinic. Ninety-four patients had nephropathy, 307
      did not. All offspring who were phenotypically normal (no hypertension, normal
      oral glucose tolerance, non-smoking) and agreed to participate were examined, 26
      from nephropathic and 30 from non-nephropathic diabetic parents. They were
      compared with 30 offspring matched for age, gender and BMI from non-diabetic
      parents as controls. We measured urinary albumin excretion under baseline
      conditions and at several time points after ingestion of 300 g cooked beef and
      submaximal treadmill exercise, respectively. In addition, casual blood pressure,
      ambulatory blood pressure, urinary albumin and urinary alpha-1-microglobulin were
      measured. Primary renal disease was excluded by clinical examination. Under
      baseline conditions, median urinary albumin excretion rate (AER; microgram/min)
      was significantly (P < 0.005) higher in offspring of nephropathic type II
      diabetic patients (7.8; range 1.04 to 19.5) than in the offspring of non
      nephropathic type II diabetic patients (4.8; 0.36 to 17.5) and controls (4.4;
      0.16 to 18.4). Submaximal treadmill exercise caused a greater proportional
      increase of AER in offspring of nephropathic type II diabetics (median 16-fold)
      than in offspring of non-nephropathic diabetic patients (6.3-fold) or controls
      (4.8-fold). In offspring of nephropathic diabetic patients casual and
      particularly ambulatory systolic blood pressures were significantly higher, but
      AER was not correlated with blood pressure. In summary, higher values, albeit
      within the normal range, for baseline and postexercise albuminuria were noted in
      phenotypically normal offspring of parents with type II diabetes and nephropathy.
      The observation suggests that changes in transglomerular albumin traffic are
      demonstrable prior to the onset of diabetes and diabetic nephropathy in subjects
      with a potential genetic predisposition to these conditions.

PMID- 9150480
TI  - Conversion from cyclosporine A to azathioprine treatment improves LDL oxidation
      in kidney transplant recipients.
AB  - The use of the immuno-suppressant cyclosporine A (CsA) after transplantation has
      been associated with less favorable plasma lipid profiles, which may contribute
      to the high incidence of cardiovascular morbidity and mortality in transplant
      recipients. Recent studies have suggested that oxidative modification of LDL
      plays an important role in the initiation and progression of atherosclerosis. It
      has also been demonstrated that CsA may facilitate lipid peroxidation in vitro
      and in vivo. Therefore, we determined several parameters of LDL oxidizability in
      renal transplant recipients who were switched from CsA to azathioprine (AZA)
      based immunosuppressive treatment. The susceptibility of LDL to in vitro
      oxidation, LDL particle size, plasma titers of IgG and IgM antibodies against
      oxidized LDL and plasma LDL subclass patterns in 19 renal transplant recipients
      were determined during CsA treatment and 16 weeks after these patients were
      converted to AZA treatment. In addition, mean arterial pressure was recorded, and
      glomerular filtration rate and renal blood flow were estimated from the clearance
      of radiolabeled thalamate and hippurate. After conversion, the plasma
      concentrations of total cholesterol, LDL cholesterol and triglyceride decreased,
      while plasma HDL cholesterol did not change. During CsA therapy plasma LDL was
      significantly more susceptible to in vitro oxidation than during AZA, as
      reflected by a longer lag phase during in vitro oxidation (98.9 +/- 24.3 vs.
      114.7 +/- 17.3 min, P = 0.031). In addition, the LDL size increased (236.5 +/-
      7.3 vs. 240.7 +/- 6.8 nm, P = 0.00001), and the titers of IgM- and IgG
      autoantibodies against oxidized LDL decreased significantly after patients were
      converted from CsA to AZA. The more atherogenic LDL subclass pattern B was
      present in 13 out of 19 patients during CsA. In five patients, pattern B changed
      into pattern A after conversion. The subclass B pattern was maintained in eight
      patients and subclass A pattern in six patients. In all patients the lag time of
      in vitro LDL oxidation increased, although the biggest changes were found in
      those patients in whom the LDL subclass changed from pattern B to pattern A. Mean
      arterial pressure decreased and renal function improved significantly after
      conversion. No correlation between parameters of lipid peroxidation and changes
      in blood pressure or renal function upon conversion, underlying renal disease,
      time since transplantation, or antihypertensive treatment was found. Our study
      demonstrates that treatment with CsA increases the susceptibility of LDL to in
      vitro oxidation, and also enhances the oxidation of LDL in vivo. In addition,
      conversion to AZA results in a more favorable lipid profile, which in combination
      with a lower arterial pressure and better renal function may decrease the risk
      for atherosclerosis. These factors may account for the cardiovascular
      complications during CsA treatment after organ transplantation, and also when CsA
      is used for other diseases.

PMID- 9150481
TI  - Microtubule active taxanes inhibit polycystic kidney disease progression in cpk
      mice.
AB  - Homozygous cpk/cpk mice develop polycystic kidney disease and die of uremia
      between the fourth and fifth weeks of age. Cpk/cpk mice treated weekly with
      paclitaxel (Taxol) can live to over six months of age. This dramatic moderation
      of polycystic kidney disease progression has been postulated to be a result of
      paclitaxel's ability to stabilize microtubules. In this study, the ability of
      taxanes with differing abilities to promote spontaneous in vitro assembly of
      tubulin dimers into microtubules were tested for their ability to inhibit the
      progression of polycystic kidney disease in polycystic cpk/cpk mice. We found
      that taxanes that are active in promoting microtubule assembly, including
      paclitaxel, 10-deactyl-taxol and cephalomannine increased the survival of
      polycystic cpk/cpk mice significantly longer than control animals. In contrast,
      the microtubule inactive taxane baccatin-III has no effect on the progression of
      renal failure in cpk/cpk mice. We conclude that the ability to promote
      microtubule assembly may be necessary for paclitaxel and related taxanes to
      modulate the progression of polycystic kidney progression in cpk/cpk mice.

PMID- 9150482
TI  - Intrarenal nitric oxide monitoring with a Clark-type electrode: potential
      pitfalls.

PMID- 9150483
TI  - Efficient morphometric analysis of glomerular mesangium in insulin-dependent
      diabetic patients with early nephropathy. The European Study of the Progression
      of Renal Disease in Type 1 (Insulin Dependent) Diabetes (ESPRIT) Study Group.

PMID- 9150484
TI  - Representational difference analysis of cDNA of genes expressed in embryonic
      kidney.
AB  - Representational difference analysis of cDNA (cDNA-RDA) is a PCR-based
      differential cloning method. It involves hybridization of two populations of cDNA
      with selective amplification of differentially expressed genes. To isolate the
      differentially expressed genes during renal development, mRNAs from embryonic
      kidneys at day 13 (E13) and postnatal kidneys from three-week-old (P3) mice were
      extracted, and double stranded cDNAs prepared. Double stranded cDNAs were
      digested with DpnII, adaptor-ligated, and amplified by PCR, using adaptor primer
      to generate "representative amplicons." These reflect the "representation" of
      most of the cDNA population. The term "amplicons" denotes amplified PCR product.
      Among the two populations of cDNA, E13 kidney cDNA was used as a "tester,"
      containing target genes, and P3 kidney cDNA as a "driver," driving the process of
      subtraction, following which, they were subjected to cDNA-RDA under low
      stringency conditions. During the first round of cDNA-RDA embryonic globin genes
      were isolated. To competitively eliminate these genes, plasmid DNAs of globin
      genes were supplemented into driver, and subjected to the second round of cDNA
      RDA. This resulted in the isolation of four cDNA clones: H19 gene, mesoderm
      specific cDNA, COL2A1 gene, and a novel cDNA. By Northern blot analyses, the H19
      gene and mesoderm-specific cDNA exhibited a high degree of developmental
      regulation, that is, they were abundantly expressed in E13 kidney, and their
      expression was barely detectable in P3 kidney. The differential developmental
      regulation of mesoderm-specific cDNA was confirmed by tissue in situ
      hybridization experiments. The COL2A1 and novel cDNA were rare transcripts in the
      embryonic Kidney. However, Southern blot analyses of representations indicated
      their up-regulated expressions in E13 kidneys. The novel gene was differentially
      expressed in 13-day embryonic lung, and Northern blot analysis revealed an
      approximately 10 Kb transcript. These results indicate that cDNA-RDA is a
      sensitive technique to identify rare transcripts with differential expression,
      and since there is a minimal chance to isolate false positive clones, cDNA-RDA
      may serve as a powerful tool for delineating up- or down-regulation of the genes
      involved in various pathological or physiological states of the kidney.

PMID- 9150485
TI  - The renal consequences of arterial hypertension.

PMID- 9150486
TI  - Practical development of genetically engineered animals as human disease models.
AB  - Since transgenic (Tg) mice were first produced in 1980, the technology to produce
      genetically engineered animals, such as Tg and knock-out mice, has advanced
      exponentially. These animals have contributed greatly to basic research at the
      molecular level and have proven to be powerful tools for elucidating complex
      biological processes. The effort that is required to develop and establish
      genetically engineered animals as models for human diseases or toxicologic
      studies is not always appreciated by researchers and laboratory animal
      scientists. Genetically engineered animals remain only candidates of defined
      animal models until they are developed for practical use, in accordance with
      their objectives, through cooperation between the researchers performing the
      experiments and laboratory animal scientists. The practical development of these
      animals consists of three steps: establishment as standardized laboratory animals
      through the setting of quality standards and the establishment of a production
      and supply system; establishment as defined animal models through confirmation of
      the usefulness and limitations of the animal in the purpose of use; and
      establishment of an in vivo experimentation system (an animal experimentation
      system), using the defined animal models. This report serves as an introduction
      to those that follow and describes our concept of how best to establish
      genetically engineered animals as valid animal models. The development of Tg mice
      carrying the poliovirus receptor gene (PVR) will be used as an example. The TgPVR
      mice were produced by the introduction of the human poliovirus receptor gene into
      the mouse genome, mainly to study the molecular mechanisms of pathogenesis of the
      virus. The value of these mice is that they mimic human and nonhuman primate
      susceptibility to poliovirus infection and thus serve as a model for the study of
      the disease and for the assessment of poliovirus vaccines. They are being touted
      as a replacement for nonhuman primates in the neurovirulence testing of oral
      poliovirus vaccine.

PMID- 9150487
TI  - Development of a neurovirulent testing system for oral poliovirus vaccine with
      transgenic mice.
AB  - Because only primates are susceptible to polioviruses, the neurovirulent safety
      and consistency of oral poliovirus vaccine (OPV) were assayed in the monkey
      neurovirulence test. After the development of transgenic (Tg) mice carrying the
      gene for human poliovirus receptor (PVR), the suitability of these mice to
      replace monkeys for OPV testing was evaluated. Two lines of Tg mice, TgPVR1 and
      TgPVR21, were tested. The TgPVR21 mice, inoculated in the spinal cord, were as
      sensitive as monkeys in discriminating between type-3 and type-2 OPV lots that
      had passed and those that had failed the monkey neurovirulence test. Results of
      the new molecular assay by polymerase chain reaction and restriction enzyme
      cleavage indicated that each OPV lot contained minuscule amounts of neurovirulent
      revertants in the viral genome. All type-3 OPV lots that failed the monkey
      neurovirulence test had higher percentages of 472-C revertants than did lots that
      passed this test. Analysis of multiple type-3 OPV lots also indicated a good
      correlation between the contents of 472-C revertants and results of the TgPVR21
      mouse test. An overview of a significant set of data suggests that the TgPVR21
      mouse model is suitable for the evaluation of type-3 and type-2 OPV. The
      necessity of the TgPVR mouse test for the neurovirulence of type-1 OPV, which is
      the most stable of the three Sabin strains, is under consideration.

PMID- 9150488
TI  - Rapid carcinogenicity testing system with transgenic mice harboring human
      prototype c-HRAS gene.
AB  - Rapid carcinogenicity tests were done with transgenic (Tg) mice human prototype c
      HRAS gene, namely BALB/cByJ x C57BL/6JF1-TgN(HRAS)2 or CB6F1-HRAS2 mice. The
      studies were conducted as the first step in the evaluation of the CB6F1-HRAS2
      mouse as a model for the rapid carcinogenicity testing system. Results of short
      term tests of various genotoxic carcinogens indicated that CB6F1-HRAS2 mice are
      more susceptible to these carcinogens than control non-Tg mice. According to the
      first-step evaluation studies, more rapid onset and a higher incidence of more
      malignant tumors can be expected with a higher probability after treatment with
      various genotoxic carcinogens in the CB6F1-HRAS2 mice than in control non-Tg
      mice. The CB6F1-HRAS2 mouse seems to be a promising candidate as an animal model
      for the development of a rapid carcinogenicity testing system.

PMID- 9150489
TI  - Activated and inactivated renin-angiotensin system in transgenic animals: from
      genes to blood pressure.
AB  - Much of our knowledge about blood pressure regulation has come from a huge number
      of biochemical, endocrinologic, pharmacologic, clinical, and physiologic studies.
      The renin-angiotensin system, composed of enzymatic and signal-transduction
      cascades, has a key role in regulating arterial blood pressure and in developing
      certain forms of experimentally induced hypertension and hypertension in human
      beings. Angiotensin peptides, the products of this system, exert a wide range of
      physiologically important effects on many tissues, including those of the
      cardiovascular system, through their actions on angiotensin receptors. Recently,
      several groups have succeeded in generating animals transgenic for the renin or
      angiotensinogen genes, or with a targeted disruption of the component genes of
      the renin-angiotensin system. This brief review describes advances of the in vivo
      analysis of blood pressure regulation by focusing on the renin-angiotensin
      system.

PMID- 9150490
TI  - Pathogenesis of Sendai virus infection in the Syrian hamster.
AB  - Young adult male Syrian hamsters were inoculated intranasally with Sendai virus,
      then killed and examined at postinoculation days (PID) 3, 5, 7, 9, 12, 16, and
      21. Evaluation included clinical assessment, histologic examination,
      immunohistochemistry, viral isolation, and antibody response. Inoculated and
      control hamsters remained asymptomatic throughout the study. There was a focal to
      segmental rhinitis involving respiratory tract epithelium lining the dorsal and
      ventral meatus and nasal septum, and segmental lesions involving all regions of
      the trachea. At PID 5 and 7, there was focal bronchitis and bronchioloalveolitis,
      respectively. In general, most lesions had resolved by PID 12, although in
      hamsters examined at PID 21, residual lesions were present in the nasal passages
      in one of three, and in the trachea in two of three animals. In immunoperoxidase
      stained preparations, viral antigen was present in the respiratory tract
      epithelium of the nasal passages and trachea beginning at PID 3, with extension
      to scattered bronchi at PID 5. Sendai virus was recovered from the lungs of
      inoculated animals at PID 5. Antibodies to Sendai virus were first detected at
      PID 7, and titers remained high throughout the remainder of the 21-day study.
      This report provides additional evidence that Syrian hamsters are susceptible to
      Sendai virus infection, and that the lesions and sites of replication in the
      upper and lower portions of the respiratory tract are similar to those observed
      in susceptible strains of laboratory mice.

PMID- 9150492
TI  - Development of a murine hypothermia model for study of respiratory tract
      influenza virus infection.
AB  - A hypothermia model was developed to predict mortality and morbidity caused by
      respiratory influenza virus infection in mice. To increase virulence, egg
      propagated influenza A/PR/8 virus was adapted for growth in mice by four blind
      serial passages. The mouse-adapted influenza A virus was then used to infect
      groups of BALB/c mice via the intranasal route, and the 50% lethal dose (LD50)
      was determined. Rectal temperature of the infected mice was monitored daily, and
      survival rate was determined at day 14 after infection. The lowest average body
      temperature recorded in infected mice was approximately 10 degrees C below that
      in noninfected mice. In mice that developed hypothermia, with body temperature of
      32 degrees C or lower, morbidity and mortality inevitably occurred. In this
      study, the LD50 and the 50% hypothermia-inducing dose (HID50) for mouse-adapted
      influenza A virus were compared and calculated to be at the same dose. These
      results suggest that the HID50 model could be used to predict mortality and
      morbidity associated with influenza virus infection in mice. This model could
      potentially be used to substantially reduce the time and extent of suffering
      inflicted on experimental animals due to viral infections, and therefore may
      serve as a more humane alternative to LD50 determinations.

PMID- 9150493
TI  - Spontaneous Leydig cell tumors in inbred laboratory mice.
AB  - Six Leydig cell tumors were identified in 6,500 male mice necropsied over a
      period of 8.5 years. All tumors developed spontaneously in BALB/cJ and BALB/cByJ
      inbred mice. When submitted for necropsy, affected mice were 8 to 9 months old.
      The incidence was calculated to be 5.5 per 100,000 males retained as breeders.
      Tumors were unilateral, with no predilection for right or left testis,
      Histologically all Leydig cell tumors were well differentiated and of the solid,
      diffuse type.

PMID- 9150491
TI  - Hepatic hemosiderosis in common marmosets, Callithrix jacchus: effect of diet on
      incidence and severity.
AB  - We examined the effect of dietary iron concentration on the incidence of hepatic
      hemosiderosis in common marmosets (Callithrix jacchus) and assessed the impact of
      hemosiderosis on animal health. Thirteen young adult common marmosets were fed
      nutritionally balanced natural-ingredient diets formulated to contain either 100
      or 500 ppm of iron. Six were fed the low-iron and seven received the high-iron
      diet. Baseline blood values and liver iron content were determined for each
      animal. Animals were weighted monthly, blood work (hematologic analysis, serum
      iron concentration, total iron-binding capacity, percent of transferrin
      saturation) was performed semi-annually, and liver biopsies for iron analysis
      were obtained after marmosets had consumed the test diets for 13 months or at
      necropsy. Midway in study, the high-iron diet was reformulated to contain 350 ppm
      of iron because of the death of a male which had consumed that diet for 7 months.
      Four of seven marmosets fed the high-iron diet died during the first year of the
      study, compared with one death in the low-iron cohort. The mean increase in liver
      iron content of the marmosets fed the high-iron diet was 6,371 micrograms/g, dry
      weight analysis. In contrast the low-iron cohort had a mean decrease of 621.5
      micrograms/g. These results indicate that liver iron content can be affected by
      dietary iron intake. The increased mortality in the marmosets fed the high-iron
      diet also suggests that hepatic hemosiderosis can be detrimental to marmoset
      health.

PMID- 9150494
TI  - Comparison of the hemodynamic and hematologic toxicity of a protamine variant
      after reversal of low-molecular-weight heparin anticoagulation in a canine model.
AB  - Using the dog as an animal model, we developed an experimental preparation to
      compare hemodynamic and hematologic toxicity of anticoagulation reversal.
      Currently, protamine sulfate reversal of standard unfractionated heparin and low
      molecular-weight heparin (LMWH) anticoagulation causes adverse side effects,
      including decreased systemic mean arterial pressure (MAP), decreased cardiac
      output (CO), decreased oxygen consumption (VO2), and thrombocytopenia. In
      addition, standard protamine is only marginally effective at reversing the factor
      Xa inhibition induced by LMWHs. We have produced protamine-like variant peptides
      to decrease the adverse responses attributed to standard protamine. The
      hemodynamic, hematologic, and coagulation effects of standard protamine and the
      protamine variant (+18RGD) were assessed after reversal of LMWH anticoagulation
      in anesthetized dogs. Flow probes and vascular catheters were surgically
      implanted for measurement of hemodynamic parameters including MAP, CO, VO2, and
      heart rate (HR). Hematologic studies (platelet and white blood cell counts) and
      coagulation studies (activated clotting time [ACT], activated partial
      thromboplastin time [aPTT], thrombin clotting time [TCT], antifactor Xa and
      antifactor IIa values) also were performed. The protamine variant +18RGD was less
      toxic, induced less thrombocytopenia, and was more effective in anticoagulation
      reversal than was standard protamine sulfate. Results of this study indicate that
      the dog may be a useful model for investigating important hemodynamic,
      hematologic, and coagulation parameters during reversal of LMWH anticoagulation
      by use of synthetic protamine variants.

PMID- 9150495
TI  - Nitric oxide inhibition causes an exaggerated pressor response in Yucatan
      miniature swine.
AB  - The involvement to nitric oxide (NO) in cardiovascular and renal function was
      evaluated in 12 anesthetized Yucatan miniature swine. The effect of NO blockade
      on blood pressure was measured in six additional conscious swine. In the
      anesthetized swine, mean arterial pressure (MAP), heart rate, glomerular
      filtration rate (GFR), and urinary excretion of water, sodium, and potassium were
      measured after systemic inhibition of NO synthesis by NG-nitro-L-arginine methyl
      ester (L-NAME), and were compared with values for a control period. After NO
      synthesis blockade, MAP increased by 63 +/- 5 mm Hg, a far greater increase than
      those observed in rats, dogs, domestic swine, or humans. The changes in GFR,
      urine flow rate (UFR), and sodium excretion (UNaV) were time-dependent. The GFR
      decreased to 50 +/- 6% of control values immediately after L-NAME administration,
      but returned to control values within 1 h. Significant increases in UFR and UNaV
      were observed only during the third experimental period, 40 to 60 min after drug
      infusion. In the conscious swine, L-NAME administration increased MAP by 24 +/- 4
      mm Hg. Administration of the sympatholytic hexamethonium bromide fully reversed
      the increase of MAP in anesthetized and conscious swine. These findings indicate
      that NO has an important role in the maintenance of cardiovascular and renal
      function in Yucatan miniature swine. The exaggerated pressor response to NO
      blockade in miniature swine appears to involve the sympathetic nervous system.

PMID- 9150496
TI  - SWR: an inbred strain suitable for generating transgenic mice.
AB  - Production of fertilized oocytes and generation of transgenic mice is generally
      more efficient using F2 hybrid embryos than embryos from inbred mice. Most F2
      hybrids are of the C57BL/6 background because of its genetic and embryologic
      features. However, our goal of developing a transgenic mouse model for rheumatoid
      arthritis necessitated using a susceptible mouse strain such as DBA/1. We
      prepared alpha and beta T-cell receptor (TCR) chain gene constructs and
      microinjected them into embryos from DBA/1, SWR, (DBA/1 x SWR)F1, and (SWR x
      DBA/1)F1 strains. We found SWR female mice to be prolific ovulators in response
      to exogenous hormones, with oocyte numbers comparable to those produced by
      (C57BL/6 x C3H)F1 female mice. Embryos from the (SWR x DBA/1)F1 or SWR strain
      were large and had prominent pronuclei, whereas (DBA/1 x SWR)F1 embryos were
      smaller and had less visible pronuclei, similar to those of DBA/1 embryos.
      Therefore, the pronuclear size and visibility are features of the SWR female mice
      and are independent of the genotype of the fertilizing spermatozoa. Resistance to
      lysis after co-injection of alpha beta TCR constructs and the efficiency of
      generating DNA-positive founders were comparable in SWR, (SWR x DBA/1)F1, and
      (C57BL6 x C3H)F2 embryos. Thus, the SWR mouse is another inbred strain, in
      addition to the FVB inbred strain, found to be highly suitable for propagation of
      transgenes. Furthermore, the SWR mouse is well defined genetically, and SWR
      females have a high ovulation rate, comparable to that of F1 hybrid mice.

PMID- 9150497
TI  - Training a large number of laboratory mice using running wheels and analyzing
      running behavior by use of a computer-assisted system.
AB  - A great many studies in the literature describe the variety of ways to provide
      physical training to small laboratory animals. Forced running on a treadmill or
      swimming training require considerable effort from the researcher, but permit the
      investigator to control the amount of exercise. Another option is to provide
      animals with access to running wheels, which they can voluntarily operate. Wheels
      can be used to investigate the running behavior of the animals. Wheel motion
      usually has been detected with magnets and microswitches and has been recorded
      using strip chart recorders or electromechanical counters. Computers also have
      been used in recording, but the measured parameters usually have been able to
      define only the total distance run in a fixed period. We designed a system, using
      running wheels, that can be used for long periods, up to years, for training a
      large number of laboratory mice simultaneously (maximal n = 96). The running
      parameters estimated by our system include running distance, speed, and time.
      Cumulative estimates of the running parameters can be produced for any period, as
      short as 1 sec. It is also easy to perform statistical analyses on the data.
      Using the system, we investigated the running behavior of 21 young C57BL/6 male
      mice. After the fast growth period, until 8 weeks of age, the mice ran 4 to 5
      km/day at an average speed of 23 m/min, and spent 3 h running each day. This took
      place during the hours of darkness.

PMID- 9150498
TI  - Breeding of bonnet monkeys (Macaca radiata) in captivity.
AB  - The results of studies on the breeding of South Indian bonnet monkeys (macaca
      radiata) over 20 years at our institution are presented. The menstrual cycle and
      hormonal changes were similar to those reported for Macaca mulatta. It was noted
      that summer amenorrhoea could be eliminated by housing the monkeys in rooms
      supplied with humidified air. Although a fertility index (proportion of animals
      becoming pregnant within three exposures to a proven fertile male) of 60 to 65%
      was achieved by random breeding, an index of 80 to 85% was achieved by controlled
      breeding (prior monitoring of serum estradiol-17 beta concentration on days 7, 8,
      9, and 10).

PMID- 9150499
TI  - Measurement of flow rates through aortic branches in the anesthetized rabbit.
AB  - The volumetric flow rates, mean and pulsatile, in the aorta and its major
      branches were measured in nonfed, anesthetized rabbits, using a transit time
      Doppler ultrasonic flowmeter. Anesthesia was maintained with isoflurane, and a
      vasodilator was applied topically during the measurements to avoid introducing
      additional flow resistance due to vasoconstriction. The cranial mesenteric and
      celiac arteries received the bulk of the aortic flow, (mean +/- SD) 29.5 +/- 6.6%
      and 23.3 +/- 5.8%, respectively, for mean flow. The brachiocephalic artery
      received as much as 14.7 +/- 3.2%, while each of the other branches received a
      considerably smaller fraction: 7.1 +/- 2.5% for the left subclavian artery, 6.2
      +/- 2.6% and 5.1 +/- 2.2%, respectively, for the right and left renal arteries,
      and 6.0 +/- 2.5% for each of the two iliac arteries. Flow divisions were nearly
      the same in paired vessels. Peak pulsatile flow divisions were similar to their
      steady flow counterparts in the brachiocephalic, left subclavian, celiac, and
      cranial mesenteric arteries, but were smaller in the renal and iliac arteries,
      although the difference was not statistically significant. Reverse flow from one
      or more of the branches back into the aorta occurred in diastole in seven of
      eight rabbits studied.

PMID- 9150500
TI  - Blood sampling technique for measurement of plasma arginine vasopressin
      concentration in conscious and unrestrained rats.
AB  - A new technique for collecting blood from conscious and unrestrained rats is
      reported. Plasma arginine vasopressin (AVP) concentration has been known to be
      influenced by various procedures used for blood collection (e.g., manual contact
      and anesthesia). In the study reported here, the improvement of the routine
      jugular vein cannula method was undertaken by extending the connection tubing to
      allow use of a swivel mechanism. Plasma AVP, glucose, and corticosterone
      concentrations in virgin rats were measured in blood samples collected by use of
      the new method and of two generally accepted methods (decapitation and routine
      jugular vein cannula methods). All values of the three parameters obtained were
      the lowest when the new method was used, suggesting that this new swivel method
      induced the least stress in the rats.

PMID- 9150501
TI  - Differentiation of EF-4 biovars by analysis of methicillin resistance.

PMID- 9150502
TI  - Asymptomatic adenoviral respiratory tract infection in guinea pigs.

PMID- 9150503
TI  - Body composition of the 12-week-old pig studied by dissection.

PMID- 9150504
TI  - Birth of normal young by microinsemination with frozen-thawed round spermatids
      collected from aged azoospermic mice.

PMID- 9150505
TI  - Fatal perforating intestinal ulceration attributable to flunixin meglumine
      overdose in rats.

PMID- 9150506
TI  - Immunologic and ultrastructural characteristics of T-cell lymphoblastic lymphoma
      associated with mast cell infiltration in a Wistar rat.

PMID- 9150507
TI  - Atrophy of the hippocampus, parietal cortex, and insula in Alzheimer's disease: a
      volumetric magnetic resonance imaging study.
AB  - The hippocampus, parietal cortex, and insula were measured on volumetric magnetic
      resonance imaging to determine whether patients with early Alzheimer's disease
      had significantly more atrophy than healthy controls. To determine whether the
      atrophy is limited to certain cortical regions, the striate cortex was measured
      because this area is not usually neuropathologically involved early in
      Alzheimer's disease. Eight mildly to moderately impaired patients who met
      National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and
      Related Disorders Association criteria for probable Alzheimer's disease and eight
      controls who matched for age, gender, and educational level were studied. Atrophy
      was quantified in the following regions: hippocampus, parietal cortex, insular
      cortex, and striate cortex. The authors found significantly more atrophy of the
      hippocampus (p < 0.0001), parietal cortex (p < 0.025), and insula (p < 0.003) in
      the Alzheimer's patients. Measures of the striate cortex did not differ between
      the groups. There were no significant left-right differences in any of the
      regions measured. Their findings show that mildly to moderately impaired
      Alzheimer's patients have significantly more atrophy of the hippocampus, parietal
      cortex, and insula than healthy age-matched controls. Furthermore, this atrophy
      is probably discrete because the groups did not differ on measures of the striate
      cortex. Selective atrophy of the parietal and insular cortices has not previously
      been reported using the authors' methodology on volumetric magnetic resonance
      imaging. Their data suggest that the insula may be involved early in Alzheimer's
      disease and that atrophy of the insular cortex may contribute to the cognitive
      deficits typical of early Alzheimer's disease.

PMID- 9150508
TI  - Orienting of visual attention in Alzheimer's disease: its implication in favor of
      the interhemispheric balance.
AB  - Visual attention in dementia of Alzheimer's disease (AD) has not been
      investigated as extensively as memory or language. The aim of this research was
      to study the orienting of attention in patients with AD (which temporo-parietal
      areas are primarily affected) compared with patients with Parkinson-Dementia,
      Parkinson's disease, and normal controls, using the Posner paradigm. Subjects
      were instructed to respond by pressing a response key after the appearance of a
      target at the same location (valid trial) or at the opposite location (invalid
      trial) indicated by a central cue (arrow). According to the experimental
      procedure developed by Posner, it has been hypothesized that parietal lobes are
      involved in "disengagement operation" (when attention has to move from one
      location to another in the controlateral field). Results showed no differences
      between AD and the other groups and between left and right hemifield. In
      conclusion, the authors did not find any sign of difficulty with disengagement,
      and results are discussed in terms of Kinsbourne's interpretation of a balance
      between hemispheres.

PMID- 9150510
TI  - Breakdown of cross-modal function in dementia.
AB  - To evaluate the possibility that specific language abnormalities in dementia are
      related to impaired cross-modal ability, the authors studied patients with
      Alzheimer's disease (which is characterized by a generalized language breakdown
      or aphasia) and patients with Parkinson's disease and dementia (a disorder
      associated more with selective deficits in naming than with aphasia). Both groups
      were initially equated for severity of dementia. Compared with nondemented
      patients with Parkinson's disease and age-equivalent healthy controls, patients
      with Alzheimer's disease and Parkinson's disease with dementia showed significant
      deficits in cross-modal ability. Moreover, the cross-modal deficits were
      significantly associated with object-naming ability. Results support the concept
      that language capacity and cross-modal functions are interrelated.

PMID- 9150509
TI  - Anosognosia and procedural learning in Alzheimer's disease.
AB  - Awareness of cognitive deficits may rely on the implicit learning of intellectual
      limitations, and anosognosia in Alzheimer's disease (AD) may result from deficits
      in implicit learning. To examine this hypothesis, a consecutive series of 55
      patients with probable AD were divided into groups with mild (n = 13), severe (n
      = 12), or no anosognosia (n = 30) and were assessed with a neuropsychological
      battery that included tests of declarative and procedural learning. Whereas there
      were no significant between-group differences in tests of declarative learning
      (the Buschke Selective Reminding Test and the Benton Visual Retention Test),
      patients with severe anosognosia showed a significantly worse performance on
      procedural learning (as measured with the Maze Learning Test) and a test
      assessing set shifting abilities (the Wisconsin Card Sorting Test) than AD
      patients without anosognosia. The authors' results suggest that deficits in
      procedural learning and anosognosia in AD may result from dysfunction in habit
      learning systems.

PMID- 9150511
TI  - Cognitive deficits distinguish patients with adolescent- and adult-onset
      schizophrenia.
AB  - Recent studies have shown that patients with schizophrenia who have an adolescent
      symptom onset (before age 21) have a worse clinical course and greater frequency
      of cerebral abnormalities than those with an adult-onset (after age 25). However,
      little is known about the neuropsychological functioning of these groups. A
      comprehensive neuropsychological examination was administered to groups of
      patients with schizophrenia with either an adolescent- or adult symptom-onset and
      a healthy control group. The adolescent-onset group performed worse than the
      adult-onset and control groups, particularly on measures of memory and executive
      function. The adult-onset group also performed worse than the controls, but to a
      lesser extent than did the adolescent-onset group. Results are discussed with
      reference to hypotheses that adolescent-onset schizophrenia represents a distinct
      neurodevelopmental disease entity.

PMID- 9150512
TI  - Differentiating patients with higher cerebral dysfunction from patients with
      psychiatric or acute medical illness using the BNI Screen for Higher Cerebral
      Functions.
AB  - The BNI Screen for Higher Cerebral Functions (BNIS) was administered to 41
      patients with known cerebral dysfunction. 22 psychiatric patients (some of whom
      were psychotic) without documented brain lesions, and 22 medical inpatients
      without neurological or psychiatric diagnoses. Patients with cerebral dysfunction
      scored significantly lower than the medical and psychiatric patients (p < 0.05).
      Utilizing the recommended cutoff score of 47, 40 of the 41 brain-dysfunctional
      patients were correctly classified as impaired, but only seven of the medical and
      five of the psychiatric patients were correctly classified. Using age-based T
      scores, 36 of the 41 brain-dysfunctional patients (87.8%) were correctly
      classified. Specificity improved slightly, but these numbers were still low
      (55%), primarily because psychotic patients performed like neurological patients
      (100%). This study provides further empirical validation of this screening
      instrument in identifying patients with brain disorders.

PMID- 9150513
TI  - Creutzfeldt-Jakob disease with features of obsessive-compulsive disorder and
      anorexia nervosa: the role of cortical-subcortical systems.
AB  - The authors examined the clinical and neuropathological characteristics of a
      patient who developed features of obsessive-compulsive disorder (OCD) and
      anorexia nervosa (AN) as the initial presentation of Creutzfeldt-Jakob disease.
      He had mild Parkinsonism and showed deficits in visual scanning, set shifting,
      graphomotor speed, sequencing, and verbal and nonverbal memory. Neuropathological
      study showed spongiosis and neuronal loss in cortical (e.g., frontal, temporal,
      parietal), and especially in subcortical structures (e.g., basal ganglia,
      thalamus). This study supports the hypothesis of abnormal frontal-striatal
      functioning in the cause of OCD, even in demented subjects. In addition, the
      authors discuss the role of frontal-temporal-subcortical dysfunction in the cause
      of acquired AN.

PMID- 9150515
TI  - A cross-cultural study on impaired self-awareness in Japanese patients with brain
      dysfunction.
AB  - Japanese patients with brain dysfunction (21 with severe traumatic brain injury
      [TBI], 21 with right, and 21 with left cerebral vascular accidents [CVA]) were
      asked to make behavioral ratings regarding their competencies in several areas.
      Relatives of patients and physical therapists who treated them also rated each
      patient's behavioral competency. Japanese patients with TBI overestimated their
      behavioral competencies compared with therapists ratings, but not relatives'
      ratings. Japanese patients with TBI overstimated self-care skills but not their
      ability to interact in socioemotional situations. Patients who had right and left
      CVA did not differ in their mean ratings of behavioral competency. Among all
      patient groups, there was no correlation between self-reported competencies and
      performance on a neuropsychological test. Family ratings of patients' behavioral
      competencies correlated with the patients' neuropsychological test performance.
      Post hoc analyses of patients with TBI suggest that speed of finger tapping
      related to an impaired self-awareness. Whereas cultural factors may influence
      self-reports of behavioral competency, patients across cultures with brain
      dysfunction seem to have reduced insight into their actual level of
      neuropsychological functioning.

PMID- 9150514
TI  - Are there sex differences in hemispatial visual neglect after unilateral stroke?
AB  - This study examined the hypothesis of greater functional asymmetry in the male
      compared with the female brain for contralesional spatial neglect. One hundred
      thirty-eight consecutive patients with computed tomography verified unilateral
      first strokes were examined within two months of onset. An aggregate measure of
      neglect was based on four clinical tasks: copying/drawing, line bisection, line
      cancellation, and figure cancellation. The incidence and severity of neglect were
      significantly greater after right-than left-hemisphere lesions and equal in men
      and women. Sex differences were not found between anterior and posterior groups
      after left- or right-hemisphere strokes. When neglect was based on different
      scores between ipsilateral versus contralesional response times on a Visual
      Search Task, the incidence was higher in females than males with right-hemisphere
      lesions.

PMID- 9150516
TI  - The Medical College of Georgia Complex Figures: reliability and preliminary
      normative data using an intentional learning paradigm in older adults.
AB  - Reliability and preliminary normative data are provided for the Medical College
      of Georgia Complex Figures (MCGCF). Forms A and B were examined in 77 healthy
      older adults, aged 55-75, and found to be of comparable difficulty. Despite the
      use of parallel forms, there was a practice effect on retesting for each of the
      recall trials of the MCGCF. There was no effect of gender on performance, but a
      correction factor is recommended for those aged 65 and older. Preliminary age
      adjusted normative tables are available, as is information to facilitate the
      interpretation of intrasubject (i.e., idiographic) performances within and
      between trials. The latter data are particularly relevant for clinical practice,
      but are rarely reported in the literature. Still lacking for the MCGCF is
      independent validation of their utility in the evaluation of clinical
      populations. Whereas examination of the various complex figures reveals no prima
      facie evidence to suggest a lack of congruence in clinical utility between the
      MCGCF and the Taylor figure, this key question can only be addressed through
      independent empirical validation.

PMID- 9150517
TI  - Septuagenarian Sydenham's with secondary hypomania.
AB  - A 74-year-old man with a remote history of Sydenham's chorea but no personal or
      family history of mood disorder had simultaneous onset of severe, generalized
      chorea and a mild manic syndrome in clear consciousness. Both chorea and
      hypomania improved after treatment with sodium valproate and clonazepam. Agitated
      delirium or mood lability have been described in Sydenham's, but this case is the
      first report of criteria-based secondary mania with probable Sydenham's chorea,
      as well as the longest reported remission between symptomatic Sydenham's
      episodes. The parallel course of this patient's hypomania and chorea supports
      current pathophysiologic theories of idiopathic mania.

PMID- 9150518
TI  - Attention deficit hyperactivity disorder associated with orbitofrontal epilepsy
      in a father and a son.
AB  - The authors report on a father and son with frontal lobe epilepsy and symptoms of
      attention deficit hyperactivity disorder (ADHD). Attention deficit hyperactivity
      is a syndrome defined by criteria that include inattention, impulsive behavior,
      impaired concentration and motor restlessness. It does not require medical or
      neurobehavioral evaluation to determine an underlying etiology. The father is a
      45-year-old man evaluated for possible ADHD. His referral came after the
      diagnosis of ADHD in his 6-year-old son who responded well to treatment with
      methylphenidate HCL. Neurobehavioral evaluation of the father suggested frontal
      lobe dysfunction. Magnetic resonance imaging and electroencephalography (EEG)
      were normal. Brain 99mTc HMPAO single-photon emission computed tomography (SPECT)
      revealed left orbitofrontal hypoperfusion. Additional history from his wife
      revealed episodic symptoms suggestive of nonconvulsive epilepsy that included
      nonresponsive staring, complex automatic behavior, and amnesic lacunas. Treatment
      of the father with carbmazepine produced dramatic improvement. Subsequent
      evaluation of his son, currently on maintenance treatment with methylphenidate
      HCL for ADHD, elicited a history consistent with atonic and simple motor partial
      epilepsy. The son's brain SPECT revealed bilateral orbitofrontal hypoperfusion
      defects. Attention deficit hyperactivity disorder is a syndrome that may be
      caused by frontal lobe lesions or epilepsy. In the setting of possible ADHD,
      neurological evaluation is warranted. Although overreliance on structural imaging
      or EEG in such an evaluation must be discouraged, brain SPECT may be useful to
      evaluate patients with symptoms of attention disorders for frontal epilepsy.

PMID- 9150519
TI  - Positive vitreous cultures from eyes without signs of infectious endophthalmitis.
AB  - BACKGROUND AND OBJECTIVE: There is little information on the rate of false
      positive vitreous cultures, because cultures from presumably sterile vitreous are
      not routinely taken in clinical practice. The objective of this study was to
      determine the rate of positive vitreous cultures from patients who have no signs
      of endophthalmitis. PATIENTS AND METHODS: Aerobic cultures from vitreous biopsies
      were taken from 36 consecutive eyes in which there was no clinical evidence of
      endophthalmitis. Effluent collected in cassettes during pars plana vitrectomies
      was processed and cultured in a standard manner. Balanced salt solution was
      processed intraoperatively through the vitrector and cultured as a negative
      control. RESULTS: Positive cultures were obtained in 8 of 36 eyes (22.2%).
      Coagulase-negative Staphylococcus and Corynebacteria accounted for 7 of the 9
      identified organisms. No organism was grown in more than one medium. None of the
      patients were treated for endophthalmitis after surgery, and none had signs of
      intraocular infection. CONCLUSIONS: A substantial number of vitrectomy cultures
      from effluent specimens grow low-virulence organisms in the absence of clinical
      signs of endophthalmitis. The absence of inflammation at the time of surgery
      suggests that these positive cultures are contaminants.

PMID- 9150520
TI  - Intraoperative mitomycin-C for glaucoma associated with ocular inflammation.
AB  - BACKGROUND AND OBJECTIVE: The authors studied the efficacy and complications of
      intraoperative mitomycin-C in glaucoma associated with ocular inflammation.
      PATIENTS AND METHODS: The authors retrospectively reviewed the medical records of
      24 consecutive patients (24 eyes) with glaucoma and ocular inflammation who had
      been treated with trabeculectomy and intraoperative mitomycin-C. Patient ages
      ranged from 10 to 83 years (mean 43 years). All patients were observed for at
      least 6 months. RESULTS: With a mean follow-up time of 14.6 months, 18 of the 24
      patients (75%) retained vision and had an intraocular pressure of 21 mm Hg or
      lower with or without medications (range 4 to 21 mm Hg; mean 13.4 mm Hg). Fifteen
      of 24 patients (62%) had an intraocular pressure of 21 mm Hg or lower with no
      medications. Three patients required tube shunt implants. One patient had a
      retinal detachment and lost light perception. One patient had endophthalmitis 14
      months after surgery. Seven of 24 patients lost two or more lines of Snellen
      acuity. CONCLUSION: Trabeculectomy with mitomycin-C can control intraocular
      pressure in glaucoma associated with ocular inflammation, but complications are
      frequent.

PMID- 9150521
TI  - Frequency of induced astigmatism following phacoemulsification with suturing
      versus without suturing.
AB  - BACKGROUND AND OBJECTIVES: To compare the postoperative astigmatism between
      sutured wounds and nonsutured wounds after cataract surgery with a 3.2-mm scleral
      tunnel incision. PATIENTS AND METHODS: One hundred ten eyes of 110 patients were
      studied. Eyes with cataracts were randomly assigned to either the sutured or the
      unsutured procedure. Identical surgical methods were used in every case except
      for wound closure technique. Data on uncorrected visual acuity and induced
      astigmatism were analyzed for 6 months after the surgery. RESULTS: Both groups
      displayed similar uncorrected visual acuity. Mean induced corneal astigmatism was
      "against-the-rule" with both techniques, and it remained stable during the study.
      No significant differences were found between the two groups (P > .1).
      CONCLUSION: This study has shown that the differences in surgically induced
      astigmatisms of sutured wounds and nonsutured wounds after cataract surgery were
      not statistically significant when a 3.2-mm self-sealing incision was used.

PMID- 9150522
TI  - Capsule excision after failed Molteno surgery.
AB  - BACKGROUND AND OBJECTIVES: To determine the frequency of scar tissue formation
      requiring surgical intervention after single-plate Molteno implantation and the
      outcome of excision of the encapsulated bleb. PATIENTS AND METHODS: A
      retrospective study was performed on 95 eyes of 79 consecutive patients who
      underwent a single-stage Molteno implantation for refractory glaucoma. Fourteen
      eyes of 12 patients developed an encapsulated bleb. A successful outcome after
      bleb excision was defined as final intraocular pressure (IOP) between 6 and 22 mm
      Hg with the same amount of medication as preoperatively or less. RESULTS: At the
      end of the mean follow-up of 30 months (range 8 to 75), the mean IOP (19.7 +/-
      3.8 mm Hg) after bleb excision was significantly lower than the preoperative IOP
      (35.2 +/- 10.1 mm Hg; P < .001). The overall conventional success rate was 75%.
      CONCLUSION: Excision of the encapsulated Molteno bleb offers an alternative in
      severely damaged eyes that have undergone several surgical procedures.

PMID- 9150523
TI  - Laser photocoagulation of diabetic macular edema.

PMID- 9150524
TI  - Photodynamic therapy for choriocapillaris using tin ethyl etiopurpurin (SnET2).
AB  - BACKGROUND AND OBJECTIVE: To investigate the use of photodynamic therapy (PDT)
      using tin ethyl etiopurpurin (SnET2) for occluding the choriocapillaris in the
      eyes of pigmented rabbits. MATERIALS AND METHODS: Following intravenous injection
      of SnET2 (0.5 and 1 mg/kg) or lipid emulsion alone, the fundus of pigmented
      rabbits (n = 21) was irradiated starting 15 to 45 minutes after photosensitizer
      injection using 664-nm light at a fluence of 300 mW/cm2 and light doses of 5 to
      20 J/cm2. Funduscopy, fluorescein angiography, and light and electron microscopy
      were performed at 1, 14, and 28 days after PDT. RESULTS: Following SnET2 and PDT,
      closure of the choriocapillaris was achieved with light doses as low as 5 J/cm2
      (17 seconds) and a drug dose of 0.5 mg/kg of SnET2. Vascular occlusion was
      documented by fluorescein angiography and histology. Photodynamic damage was
      noted in the choriocapillary endothelial cells. Retinal pigment epithelial damage
      and outer retinal damage were also observed. No funduscopic, angiographic, or
      histologic findings were present in the eyes of pigmented control rabbits.
      CONCLUSIONS: PDT with SnET2 was effective in this animal model, using low levels
      of activating light for the occlusion of the choriocapillaris. This has clinical
      implications for the treatment of choroidal neovascularization and could be a
      more selective therapy than thermal laser photocoagulation.

PMID- 9150525
TI  - Cornea and iris changes in congenital ectropion uvea after trabeculotomy.
AB  - This article details a previously undescribed complication of trabeculotomy
      occurring in a patient with congenital ectropion uvea and discusses its possible
      association with an anterior chamber membrane. A 6-year-old boy with congenital
      ectropion uvea underwent trabeculotomy. After the trabeculotome was swept into
      the anterior chamber, multiple ovoid and round endothelial and posterior stromal
      opacities developed in the cornea, and new areas of iris surface irregularities
      appeared. This is the first reported case of corneal endothelial and iris changes
      occurring in a patient with congenital ectropion uvea after trabeculotomy without
      direct endothelial or iris contact from the trabeculotome. The exact cause of
      these changes is unknown.

PMID- 9150526
TI  - Traumatic cataract and Wieger's ligament.
AB  - The objective of this study was to determine the relationship between posterior
      subcapsular contusion cataract and Wieger's ligament. Two clinical cases of
      traumatic cataract, occurring in young patients, were analyzed. In neither case
      was there evidence of penetrating or perforating injuries to the globe. During
      cataract extraction a smooth oval defect in the posterior capsule was observed;
      however, there was no evidence of intraoperative capsular damage. The outline of
      the defect was consistent with the border of Wieger's ligament. It appears that
      blunt trauma avulsed this region of lens capsule, resulting in these findings.

PMID- 9150527
TI  - Measurement of head-turn in ocular torticollis.
AB  - There is a need for a simple and accurate method to measure head-turn in patients
      who suffer from torticollis secondary to ocular disease. In the technique
      described here, a fixation object is moved from a point in front of the patient
      to a point at which the patient's face is straight. The distance that the object
      is moved is proportional to the amount of head-turn the patient has. With a
      simple mathematical calculation, the angle of head-turn can be determined, even
      during a routine clinical evaluation.

PMID- 9150528
TI  - Corneal autograft patches for covering exposed transscleral sutures.
AB  - This article details the authors' experience with a relatively unknown technique
      for covering exposed ends of transscleral sutures. During combined transscleral
      suturing of a posterior chamber intraocular lens (PC IOL) with a penetrating
      keratoplasty, buttons from the excised recipient cornea are sutured with 10-0
      nylon over the protruding suture ends. This technique has been used successfully
      in four cases.

PMID- 9150529
TI  - Human dura mater as a wrapping material for hydroxyapatite implantation in the
      anophthalmic socket.
AB  - Homologous sclera and autologous fascia lata have been accepted as common
      wrapping materials for hydroxyapatite implantation; however, various problems
      have been observed, such as the risk of transmittable diseases such as AIDS or
      hepatitis. This report details the use of cadaver dura mater to wrap
      hydroxyapatite implants. For 73 eyes of 73 patients with hydroxyapatite
      implantation, cadaver dura mater was used to wrap the hydroxyapatite after
      enucleation or secondary implantation. Of the 73 patients, 20 had conjunctival
      erosion; however, all of the patients but 1 healed spontaneously within an
      average of 22 days. Only 1 of the 73 patients progressed to implant exposure
      requiring a dermis graft. The authors suggest that cadaver dura mater is a
      suitable wrapping material for hydroxyapatite implantation.

PMID- 9150530
TI  - More on procedures in the evaluation of the febrile pediatric patient.

PMID- 9150531
TI  - More on asthma and cough.

PMID- 9150532
TI  - Dad, did you take a good look at this baby?

PMID- 9150533
TI  - Pediatrics and child sexual abuse: where we've been and where we're going.
AB  - Those of us in pediatrics who take a special interest in child abuse have had a
      unique opportunity to watch an important body of knowledge develop. Our challenge
      for the next century is to continue to build our knowledge base, to train young
      physicians in the care of abused and neglected children, and to remain committed
      to the concept that every child in this country deserves a wholesome, healthy
      childhood.

PMID- 9150534
TI  - Preparation for child abuse litigation: perspectives of the prosecutor and the
      pediatrician.

PMID- 9150535
TI  - Sexual abuse and adolescents.

PMID- 9150536
TI  - The pediatrician's role in child abuse interviewing.
AB  - The history of sexual abuse that a child gives to the pediatrician may be the
      single most important factor in determining if a child has been abused. Most
      children have completely normal anogenital examinations; very rarely is
      definitive forensic evidence obtained or a sexually transmitted disease
      discovered. Physicians, in general, are given unique authority and privilege in
      reporting such hearsay evidence. The pediatrician often is the first professional
      with whom a child has contact when an allegation of abuse is made. Child
      protective issues then become paramount. It is important, therefore, for the
      physician to have the basic skills and knowledge of the developmentally
      appropriate approach to interviewing a child. How that interview is preserved and
      documented is also critically important and will be scrutinized in any legal
      proceedings. The physician's interview should not replace a skilled forensic
      interview but be considered a supplement, whose purpose is foremost the health,
      well-being, and protection of the child.

PMID- 9150537
TI  - Examination for sexual abuse in prepubertal children: an update.
AB  - The complete physical examination of prepubertal children should always include a
      genital examination. Most children, even those who have been sexually abused,
      will have a normal genital examination. A child's acceptance and tolerance for
      this aspect of the examination will be enhanced by use of the techniques
      described. Sexually abused children may be identified through routine review of
      systems and history, including behavioral and psychosocial, and open-ended
      questions regarding sexual abuse. Regular genital examinations will also help to
      identify sexually abused children. Although the diagnosis of sexual abuse can
      never rely solely on physical findings, abnormal findings suspicious for sexual
      abuse are significantly more useful if there have been prior documented normal
      examinations. When sexually abused children initially present to their medical
      practitioner, the practitioner should obtain a complete medical and psychosocial
      history and perform a thorough examination. The practitioner need not be an
      expert in the interpretation of the possible legal significance of specific
      genital findings but should recognize normal, abnormal, and suspicious findings.
      Reassurance from a trusted practitioner relating to a normal body can be the most
      valuable treatment for a child's emotional healing. Practitioners need to be
      aware of the resources in their community for medical evaluations for sexual
      abuse, legal investigations, and mental health referrals. If there is a local
      center for child abuse evaluations, such as a Child Advocacy Center or Center of
      Excellence for child protection, practitioners should consider referrals to and
      consultations with these resources.

PMID- 9150538
TI  - Anogenital skin diseases of childhood.
AB  - Evaluation of anogenital lesions in children is a challenging problem. The
      differential diagnosis includes a spectrum of traumatic, infectious, neoplastic,
      and genetic disorders. The possibility of sexual abuse should always be
      considered and investigated as indicated. A systematic work-up will expedite the
      correct diagnosis and limit unnecessary anxiety for parents, children, and
      physicians. Referral to a center that provides specialized service for the
      evaluation and treatment of these disorders may be indicated.

PMID- 9150539
TI  - Epizootic disseminated toxoplasmosis in captive slender-tailed meerkats (Suricata
      suricatta).
AB  - Fatal disseminated toxoplasmosis was diagnosed in seven captive slender-tailed
      meerkats (Suricata suricatta) according to clinicopathologic findings and
      immunohistochemistry. Five of nine meerkats died during an outbreak in late 1994.
      These included four kits (2.5 to 4.5 months old) and a 4-year-old meerkat. Two
      other meerkats, both adults, died in 1992 and 1995. Respiratory insufficiency
      (4/7) and incoordination (3/7) were the most consistent clinical signs. although
      two of seven meerkats died unexpectedly. At necropsy, the lungs were reddened and
      noncollapsed (6/7), and had multiple pale round foci (4/7). Yellow foci of
      necrosis in mesenteric lymph nodes (4/7), splenomegaly (3/7), and
      hydropericardium (3/7) were other common gross findings. Microscopically,
      interstitial pneumonia was present in all seven meerkats, being acute to subacute
      in six of them. Type 2 pneumocyte hyperplasia, aggregates of foamy macrophages,
      and giant cells were consistently seen. Multifocal to locally extensive necrosis
      of mesenteric lymph nodes (4/7), mild to severe multifocal necrotizing hepatitis
      (5/6), and mild nonsuppurative encephalitis (4/6) were also seen. Toxoplasma-like
      organisms were consistently associated with these lesions and were stained by the
      avidin biotin peroxidase procedure with an antiserum that does not cross-react
      with Neospora caninum. Meerkats were most likely infected after an oral, primary
      exposure to Toxoplasma. Several observations indicate that meerkats may be highly
      susceptible to toxoplasmosis.

PMID- 9150540
TI  - Multiple pigmented cutaneous papules associated with a novel canine
      papillomavirus in an immunosuppressed dog.
AB  - Cutaneous papillomavirus infection was diagnosed in a 6-year-old female Boxer dog
      that was under long-term corticosteroid therapy for atopic dermatitis. Multiple
      black, rounded papules were present on the ventral skin. Spontaneous regression
      occurred within 3 weeks after cessation of corticosteroids. Histologically, the
      lesions consisted of well-demarcated cup-shaped foci of epidermal endophytic
      hyperplasia with marked parakeratosis. In the upper stratum spinosum and in the
      stratum granulosum, solitary or small collections of enlarged keratinocytes were
      observed with basophilic intranuclear inclusion bodies and a single eosinophilic
      fibrillar cytoplasmic inclusion. Ultrastructurally, viruslike particles (40-45 nm
      in diameter) were observed within the nucleus, free or aggregated in crystalline
      arrays. Undulating fibrillar material, thought to be a modified keratin protein,
      was observed in the cytoplasmic inclusion. Immunohistochemistry, restriction
      enzyme analysis, and molecular hybridization experiments indicated that these
      distinctive clinical, histologic, and cytologic features were associated with a
      novel canine papillomavirus.

PMID- 9150541
TI  - Fatal infections with Balamuthia mandrillaris (a free-living amoeba) in gorillas
      and other Old World primates.
AB  - Balamuthia mandrillaris is a newly described free-living amoeba capable of
      causing fatal meningoencephalitis in humans and animals. Because the number of
      human cases is rapidly increasing, this infection is now considered an important
      emerging disease by the medical community. A retrospective review of the
      pathology database for the Zoological Society of San Diego (the San Diego Zoo and
      San Diego Wild Animal Park) for the period July 1965 through December 1994
      revealed five cases of amoebic meningoencephalitis, all in Old World primates.
      The infected animals were a 3-year, 10-month-old female mandrill (Papio sphinx),
      from which the original isolation of B. mandrillaris was made, a 5-year-old male
      white-cheeked gibbon (Hylobates concolor leucogenys), a 1-year-old female western
      lowland gorilla (Gorilla gorilla gorilla), a 13-year, 5-month-old male western
      lowland gorilla, and a 6-year-old female Kikuyu colobus monkey (Colobus guereza
      kikuyuensis). Two different disease patterns were identified: the gibbon,
      mandrill, and 1-year-old gorilla had an acute to subacute necrotizing amoebic
      meningoencephalitis with a short clinical course, and the adult gorilla and
      colobus monkey had a granulomatous amoebic meningoencephalitis with extraneural
      fibrogranulomatous inflammatory lesions and a long clinical course. Indirect
      immunofluorescent staining of amoebas in brain sections with a Balamuthia
      specific polyclonal antibody was positive in all five animals. Indirect
      immunofluorescent staining for several species of Acanthamoeba, Naegleria
      fowleri, and Hartmanella vermiformis was negative. Direct examination of water
      and soil samples from the gorilla and former mandrill enclosures revealed
      unidentified amoebas in 11/27 samples, but intraperitoneal inoculations in mice
      failed to induce disease. Attempts to isolate amoebas from frozen tissues from
      the adult male gorilla were unsuccessful.

PMID- 9150542
TI  - The equine endometrial mast cell during the puerperal period: evaluation of mast
      cell numbers and types in comparison to other inflammatory changes.
AB  - Endometrial biopsies of 44 broodmares were histologically examined on days 3, 6,
      and 9 postpartum. The mares were subdivided into three groups according to the
      course of the puerperal period. In 29 mares, parturition and expulsion of the
      placenta was normal, six mares showed dystocia, and in nine mares, the placenta
      was retained for > 2 hours. Tissue samples were evaluated histologically, and the
      average numbers of granulocytes, lymphocytes, macrophages, siderophages, and mast
      cells was determined. Protease content of mast cells was examined with a double
      enzyme immunohistochemical staining technique, using a histochemical reaction for
      chloroacetate esterase and fast blue to detect chymase activity and an
      immunohistochemical staining method with a polyclonal antibody and fast red for
      the detection of tryptase. Analyzing the cell numbers using the statistical
      software Statistica, a marked inflammatory reaction was observed in the
      endometrium postpartum. Although the number of granulocytes decreased during the
      first 9 days postpartum, the number of lymphocytes, macrophages, and siderophages
      increased. No significant difference in the number of any of these cell types
      could be demonstrated in the three different courses of the puerperal period,
      although the numbers of these cells seemed to be lower in mares with dystocia. In
      contrast with other cells, no change in the number of endometrial mast cells was
      observed during the puerperal period, but a significantly lower number were found
      in the endometrium of mares with retained placenta. The enzyme
      immunohistochemical double-labeling technique could demonstrate only tryptase
      positive mast cells; no chymase activity was detectable in any endometrial mast
      cells. The number of mast cells detected with the metachromatic staining
      technique was significantly higher than that detected with double labeling. These
      results support the hypothesis that a sufficient number of mast cells may be
      necessary for a normal postnatal period and suggest a mast cell subtype in the
      equine endometrium that is tryptase and chymase negative.

PMID- 9150543
TI  - Cutaneous malignant melanomas in 57 cats: identification of (amelanotic) signet
      ring and balloon cell types and verification of their origin by
      immunohistochemistry, electron microscopy, and in situ hybridization.
AB  - Cutaneous malignant melanomas in cats, both melanotic and amelanotic, were
      diagnosed in 57 of 1.530 skin tumors during the period 1991-1995. All melanomas
      occurred in domestic shorthaircats of ages 3-19 years (mean = 11.5 years).
      Postmortem examination was performed on 16 cats. All had metastases in the
      regional lymph node and several organ systems. The average time of survival after
      surgical removal of the tumor was 4.5 months. Histologically, five types of
      melanomas could be distinguished: epithelioid, spindle, mixed, signet-ring, and
      balloon cell. Whereas all epithelioid, spindle, and mixed epithelioid/spindle
      cell types showed pigmentation, signet-ring and balloon cell types were often
      amelanotic. Immunohistochemical examination of the melanomas revealed a positive
      staining for S-100, vimentin, and neuron-specific enolase. The melanomas were
      negative for muscle cell markers, except in some of the signet-ring cell
      melanomas; 13 of 21 tumors showed a weak positive staining for polyclonal desmin.
      Electron microscopic examination of signet-ring cell melanomas revealed an
      abundance of intermediate filaments, whereas in some of these tumors a few cells
      with melanosomes were found. Nonisotopic in situ hybridization for mRNA encoding
      for tyrosinase verified the melanocytic origin of the amelanotic signet-ring and
      balloon cell melanomas.

PMID- 9150544
TI  - Temporal and morphologic characterization of the distribution of porcine
      reproductive and respiratory syndrome virus (PRRSV) by in situ hybridization in
      pigs infected with isolates of PRRSV that differ in virulence.
AB  - Three groups of 5-week-old cesarian-derived, colostrum-deprived pigs were
      inoculated intranasally with either a high-virulence isolate (VR2385) or a low
      virulence isolate (VR2431) of porcine reproductive and respiratory syndrome virus
      (PRRSV) or with uninfected cell culture and media. Formalin-fixed, paraffin
      embedded tissues from pigs euthanatized at 10, 21, and 28 days post-inoculation
      were examined by in situ hybridization for PRRSV nucleic acid using a digoxigenin
      labeled antisense RNA probe approximately 1,000 nucleotides in length. Alveolar
      macrophages were positive in the lungs of 9/9, 2/2, and 0/2 VR2385-inoculated
      pigs and 7/9, 1/2, and 2/3 VR2431-inoculated pigs at 10, 21, and 28 days post
      inoculation, respectively. More positive cells were detected in lungs from VR2385
      inoculated pigs compared to VR2431-inoculated pigs at 10 and 21 days post
      inoculation. Positive cells within lymph nodes were tingible body macrophages in
      germinal centers and macrophages or interdigitating dendritic cells within the
      paracortical area. VR2385 was detected in the tracheobronchial lymph node (TBLN)
      and mediastinal lymph node (MLN) of 7/9 and 9/9 pigs at 10 days post-inoculation,
      but was only detected in the TBLN of 1/2 and 0/2 pigs and in the MLN of 0/2 and
      1/2 pigs at 21 and 28 days post-inoculation, respectively. In contrast, VR2431
      was detected in teh TBLN and MLN of 5/9 and 2/9 pigs at 10 days post-inoculation
      and in the TBLN of 0/2 and 1/3 pigs and in the MLN of 0/2 and 0/3 pigs at 21 and
      28 days post-inoculation, respectively. There were more positive cells in TBLN
      and MLN in pigs inoculated with VR2385 at 10 days post-inoculation. Macrophages
      located at the epithelial-lymphoid interface of tonsilar crypts and within the
      paracortical areas were positive in tonsils of 9/9, 2/2, and 1/2 VR2385
      inoculated pigs and 7/9, 1/2, and 1/3 VR2431-inoculated pigs at 10, 21, and 28
      days post-inoculation, respectively. Positive cells in the thymic medulla were
      multinucleate and were only detected at 10 days post-inoculation in 2/9 VR2385
      inoculated pigs and 4/9 VR2431-inoculated pigs. Positive cells within the spleen
      were few, spindle-shaped, located within smooth muscle trabecula, and only
      present at 10 days post-inoculation in 3/9 VR2385-inoculated pigs. We conclude
      that the tissue tropism and distribution of positive cells within tissues is
      similar for VR2385 and VR2431. However, tissues from more pigs and more cells
      within tissues were positive in pigs inoculated with VR2385 than VR2431 at 10 and
      21 days post-inoculation. These findings indicate that the more virulent isolate
      VR2385 may replicate better in vivo than the less virulent isolate VR2431. This
      supports the hypothesis that an increased ability to replicate in vivo
      contributes to increased virulence of PRRSV.

PMID- 9150545
TI  - Naturally occurring herpes simplex encephalitis in a domestic rabbit (Oryctolagus
      cuniculus).
AB  - An approximately 1-year-old domestic rabbit showed severe neurologic signs with
      circling and turning somersaults. Histologically, a nonsuppurative
      meningoencephalitis with neuronal cell necrosis and numerous intranuclear
      inclusion bodies in neurons and glial cells was found. Electron microscopic
      examination revealed herpesvirus particles in affected cells. A human herpes
      simplex virus was identified by means of immunocytochemistry and in situ
      hybridization as the causal agent and was further classified as herpes simplex
      virus 1 by polymerase chain reaction analysis. Because encephalitis is easily
      induced in rabbits by experimental infection with herpes simplex virus, the
      source of infection is suspected to be a human with herpes labialis who had close
      contact with the rabbit.

PMID- 9150546
TI  - T-cell-rich B-cell lymphoma in a cat.
AB  - T-cell-rich B-cell lymphoma is a neoplasm recognized in humans in which a
      neoplastic proliferation of large B lymphocytes is present amid a background of
      reactive T lymphocytes. A 13-year-old Domestic Shorthair cat developed a mass in
      the region of the left parotid gland. Histologically, the mass was composed of
      scattered large atypical cells within a dense background of uniform small
      lymphoid cells. Immunohistochemically, the large cells were uniformly labeled
      using antiserum directed against the B-lymphocyte marker BLA.36, whereas labeling
      of nearly all of the small cells was limited to the T-lymphocyte marker CD3. The
      histomorphologic and immunohistochemical features of this unique feline neoplasm
      are characteristic of T-cell-rich B-cell lymphoma of humans.

PMID- 9150548
TI  - Immunohistochemical demonstration of equine herpesvirus-1 antigen in neurons and
      astrocytes of horses with acute paralysis.
AB  - Equine herpesvirus-1 (EHV-1) infection in a few widely scattered neurons and
      astrocytes plus endothelial cells in brain and spinal cord of two horses with
      naturally occurring paralytic disease was demonstrated by use of an
      immunoperoxidase technique. These horses were euthanatized less than 48 hours
      after the onset of clinical signs. No staining for EHV-1 was demonstrated in
      brain or spinal cord of three horses that had a longer duration of clinical
      disease or in two uninfected horses.

PMID- 9150547
TI  - Gastric ulcer associated with a Helicobacter-like organism in a cougar (Felis
      concolor).
AB  - A 12-year-old captive female cougar (Felis concolor) died following perforation
      of a gastric ulcer. Histologically, erosions and ulcers were present in the
      antral area of the stomach. Fibroplasia and infiltrates of neutrophils bordered
      the ulcers. Modified Steiner silver stain revealed numerous tightly coiled
      helical bacteria. The bacteria stained positively with a rabbit polyclonal anti
      Helicobacter pylori antibody. Morphology, location, and positive
      immunohistochemical staining suggests that the organism is a Helicobacter.

PMID- 9150549
TI  - Exocrine pancreatic insufficiency in a yellow-naped Amazon (Amazona ochrocephala)
      with pancreatic adenocarcinoma.
AB  - This report describes exocrine pancreatic insufficiency in a yellow-naped Amazon
      (Amazona ochrocephala) with complete effacement of the pancreas by a pancreatic
      adenocarcinoma. The bird presented with a 3-month history of weight loss and
      voluminous, foul-smelling droppings. Clinically, routine hematologic findings
      were normal and fecal tests were performed to evaluate exocrine pancreatic
      function. The fecal function tests were positive for neutral and split fats and
      negative for trypsin. Oral administration of corn oil did not result in elevation
      of blood triglyceride levels. Two days later, the triglyceride tolerance test was
      repeated using corn oil mixed with pancreatic enzymes. This time, there was a 70%
      elevation of blood triglyceride levels. Because of a poor prognosis, the bird was
      euthanatized. At necropsy, the pancreas was diffusely enlarged, white, nodular,
      and firm. The liver contained multiple, 1-2-mm-diameter, randomly located, tan
      nodules. Microscopically, the pancreas was effaced by numerous lobules of
      neoplastic ductular structures surrounded by abundant fibrous connective tissue.
      In the liver, the hepatic parenchyma was replaced by multiple, well-demarcated,
      nonencapsulated foci of neoplastic tissue similar to that in the pancreas.

PMID- 9150550
TI  - Ovarian steroid cell tumor resembling luteoma associated with
      hyperadrenocorticism (Cushing's disease) in a dog.
AB  - An ovarian steroid cell tumor was diagnosed in a 6.5-year-old female Rottweiler.
      The animal was polydipsic and polyuric, with an enlarged, pot-bellied abdomen.
      Radiographs and ultrasound examinations revealed an approximately 13-cm-diameter
      cystic mass below the right kidney. A low-dose dexamethasone suppression test was
      consistent with hyperadrenocorticism. Surgical exploration revealed an enlarged,
      lobulated left ovary approximately 10 cm in diameter, weighing 550 gs.
      Histologically, the ovarian tumor consisted of dense sheets and nests of round to
      polyhedral cells with abundant, finely vesiculated cytoplasm. The overall
      features were most consistent with ovarian steroid cells tumor resembling luteoma
      and associated with hyperadrenocorticism.

PMID- 9150551
TI  - Cell adhesion molecules--update.
AB  - Cell adhesion molecules are glycoproteins expressed on the cell surface and play
      an important role in inflammatory as well as neoplastic diseases. There are four
      main groups: the integrin family, the immunoglobulin superfamily, selectins, and
      cadherins. The integrin family has eight subfamilies, designated as beta 1
      through beta 8. The most widely studied subfamilies are beta 1 (CD29, very late
      activation [VLA] members), beta 2 (leukocyte integrins such as CD11a/CD18,
      CD11b/CD18, CD11c/CD18, and alpha d beta 2), beta 3 (CD61, cytoadhesions), and
      beta 7 (alpha 4 beta 7 and alpha E beta 7). The immunoglobulin superfamily
      includes leukocyte function antigen-2 (LFA-2 or CD2), leukocyte function antigen
      3 (LFA-3 or CD58), intercellular adhesion molecules (ICAMs), vascular adhesion
      molecule-1 (VCAM-1), platelet-endothelial cell adhesion molecule-1 (PE-CAM-1),
      and mucosal addressin cell adhesion molecule-1 (MAdCAM-1). The selectin family
      includes E-selectin (CD62E), P-selectin (CD62P), and L-selectin (CD62L).
      Cadherins are major cell-cell adhesion molecules and include epithelial (E),
      placental (P), and neural (N) subclasses. The binding sites (ligands/receptors)
      are different for each of these cell adhesion molecules (e.g., ICAM binds to
      CD11/CD18; VCAM-1 binds to VLA-4). The specific cell adhesion molecules and their
      ligands that may be involved in pathologic conditions and potential therapeutic
      strategies by modulating the expression of these molecules will be discussed.

PMID- 9150552
TI  - Dubbing animal diseases with color.

PMID- 9150553
TI  - Comparison of three methods of ulnar fixation in horses.
AB  - OBJECTIVE: This study compares the mechanical properties of three methods of
      equine ulnar fixation: dynamic compression plating, pins and wires tension band,
      and a prototype grip system. STUDY DESIGN: The mechanical properties of dynamic
      compression plating, pins and wires tension band, and a prototype grip system
      repair of equine ulnar fractures were evaluated in a cadaveric osteotomy model.
      ANIMALS OR SAMPLE POPULATION: Fifteen pairs of the radius and ulna from equine
      cadavers. METHODS: The three repair techniques were evaluated to mimic the pull
      of the triceps brachii muscle in single cycle to failure and in cyclic fatigue
      loading. Single cycle results were evaluated as the axial and angular
      displacement. Cyclic fatigue results were evaluated as the number of cycles to
      failure. RESULTS: Dynamic compression plate fixation and pins and wires tension
      band had significantly less axial displacement of the proximal fragment than the
      grip system (P < .05). No significant difference in angular rotation of the
      proximal fragment was present between the three techniques. Dynamic compression
      plating had significantly greater fatigue resistance than the grip system (P <
      .05). Cyclic failure was characterized by screw loosening or breakage and wire
      breakage. CONCLUSIONS: Dynamic compression plates were better than the other
      techniques at maintaining compression of a transverse ulnar osteotomy at the
      level of the anconeal process just proximal to the trochlear notch. CLINICAL
      RELEVANCE: Knowledge of fixation technique mechanical properties is essential for
      surgeons to select the proper method of fracture repair.

PMID- 9150554
TI  - The effects of ischemia and reperfusion on mucosal respiratory function,
      adenosine triphosphate, electrolyte, and water content in the ascending colon of
      ponies.
AB  - OBJECTIVE: The purpose of this study was to examine the effects of ischemia and
      reperfusion on the biochemical integrity of equine colonic mucosa to assess the
      relative roles of ischemic- and reperfusion-induced damage. STUDY DESIGN: Two
      hours of no-flow ischemia experimentally induced by 720 degrees counterclockwise
      ascending colon volvulus followed by 2 hours reperfusion after derotation.
      ANIMALS: Ten ponies. METHODS: Ascending colon biopsies were obtained every hour
      for measurement of mucosal adenosine triphosphate (ATP), water, sodium, and
      potassium content. Additional samples were homogenized for assay of mitochondrial
      respiratory function. RESULTS: ATP content diminished 92% after ischemia and
      recovered to only 44% of control levels (P < .001 versus controls) after 2 hours
      reperfusion. Reperfusion increased mucosal water and decreased sodium and
      potassium content for the duration of the experiment. Both NADH-(pyruvate) and
      FADH-linked (succinate) respiration decreased after ischemia and did not recover
      during reperfusion indicating electron transport chain dysfunction. CONCLUSIONS:
      Two hours ischemia induced severe metabolic dysfunction in equine colon mucosa
      which persisted throughout reperfusion. Unequivocal evidence of injury specific
      to reperfusion was not observed in this study suggesting that much of the damage
      observed during reperfusion may be a continuation of injury induced during the
      ischemic period and not specific to reperfusion per se. CLINICAL RELEVANCE: This
      study suggests that greater efforts to metabolically support ischemically injured
      mucosa may be an important aspect of obtaining improved survival of horses
      affected by ascending colon volvulus (ACV).

PMID- 9150555
TI  - Role of endothelium and nitric oxide in the response of equine colonic arterial
      rings to vasoconstrictor agents.
AB  - OBJECTIVE: To determine the in vitro contractile responses of equine colonic
      arteries to angiotensin II, histamine, serotonin, norepinephrine, prostaglandin
      F2 alpha, vasopressin, and a thromboxane-B2-analogue. STUDY DESIGN: The tension
      generated in colonic arterial rings placed in organ baths with oxygenated
      Tyrode's solution at 37 degrees C after exposure to the previously mentioned
      chemical agents was measured using force-transducers interfaced with a polygraph.
      SAMPLE POPULATION: Large colon arterial rings collected from eight horses.
      METHODS: The rings were allowed to equilibrate for 45 minutes after applying 2 g
      tension. Bath solution was replaced and tension reapplied at 15-minute intervals.
      Cumulative-concentration-responses were determined for concentrations ranging
      from 10(-8) M to 10(-4) M on three vessel groups namely endothelium intact,
      endothelium denuded, and L-NAME treated. The maximal response for each vessel was
      considered as 100%; responses to lower concentrations were calculated as a
      percentage of the maximum. The EC50 value was determined for each concentration
      response relationship of each agent. RESULTS: Vessels with denuded endothelium or
      those incubated with L-NAME had greater contractile responses. Angiotensin,
      histamine, serotonin, and norepinephrine produced greater maximal responses than
      the other agents. Endothelium denuded rings had lower EC50 values. Responses to
      norepinephrine and serotonin were affected less by denudation. CONCLUSIONS:
      Endothelium plays an important role in modulating responses of colonic arterial
      rings to contractile agents. Endothelium-derived vasodilators, other than nitric
      oxide, may modulate contractile responses of equine colonic arteries. CLINICAL
      RELEVANCE: Endothelial damage associated with colonic vovulus may be a major
      factor for sustained reduced perfusion after surgical correction.

PMID- 9150556
TI  - Endogenous benzodiazepine activity in the peripheral and portal blood of dogs
      with congenital portosystemic shunts.
AB  - OBJECTIVE: The purpose of this study was to determine whether an endogenous
      benzodiazepine receptor ligand (EBZ) was present in the arterial and portal blood
      of dogs with congenital portosystemic shunts (CPSS). STUDY DESIGN: The presence
      or absence of an EBZ was determined by the collection of systemic and portal
      blood from dogs with CPSS. ANIMALS: Fifteen client-owned dogs with a confirmed
      CPSS. All dogs had historical signs compatible with hepatic encephalopathy. Eight
      healthy dogs were used as controls. METHODS: In all dogs, systemic blood samples
      were collected after they were anesthetized. Portal blood samples were collected
      intraoperatively. EBZ was measured by radioreceptor assay. RESULTS: In 10 of 15
      dogs, the portal blood concentration of EBZ was significantly elevated compared
      with normal dogs (mean, 13.2 +/- 18.55 ng/mL). Five dogs had elevated systemic
      blood EBZ levels (mean, 8.2 +/- 16.08 ng/mL). Eleven of 15 dogs had a higher
      portal than systemic blood concentration of EBZ. In contrast, control dogs had
      extremely low EBZ concentrations detected in their portal blood (mean, 0.16 +/-
      0.3 ng/mL) and systemic blood (0 ng/mL). The mean portal and systemic blood
      concentrations in dogs with CPSS were significantly greater than in control dogs
      (P < .05). CONCLUSIONS: Elevated blood levels of EBZ were found in dogs with
      CPSS. The portosystemic gradient noted in 11 dogs suggests the gastrointestinal
      tract as a possible source for the endogenous ligand. CLINICAL RELEVANCE:
      Generalized motor seizures have been reported in dogs after surgical correction
      of CPSS. If the presence of a CPSS results in stimulation of brain receptors for
      benzodiazepines, post-CPSS ligation seizures may result from a withdrawal of EBZ
      after ligation of the portosystemic shunt.

PMID- 9150557
TI  - Acute, unilateral transverse sinus occlusion during craniectomy in seven dogs
      with space-occupying intracranial disease.
AB  - OBJECTIVE: The purpose of this study was to determine the effect of acute,
      unilateral transverse sinus occlusion on intracranial pressure (ICP) and
      postoperative mortality in dogs with structural intracranial disease. STUDY
      DESIGN: Affected dogs had a single transverse sinus occluded during craniectomy
      for intracranial mass biopsy or removal. ANIMALS: Seven dogs with space-occupying
      intracranial disease in the cerebellopontine angle area. METHODS: The ipsilateral
      transverse sinus was permanently occluded during the surgical approach to the
      intracranial lesion to increase surgical exposure by allowing a caudal lateral
      rostrotentorial craniectomy to be combined with a suboccipital craniectomy. In
      five dogs, intracranial pressure was monitored during surgery using a fiberoptic
      intracranial pressure monitoring device. RESULTS: Initial ICP varied among dogs,
      ranging from 7 to 21 mm Hg. Intracranial pressure, however, decreased in all dogs
      after craniectomy and durotomy (P < .05). No increase in intracranial pressure
      occurred after transverse sinus occlusion (P = .42). All dogs survived the
      surgical procedure. CONCLUSIONS: Acute, unilateral transverse sinus occlusion
      during craniectomy in dogs with space-occupying intracranial lesions did not
      result in significant increases in ICP or intraoperative mortality. CLINICAL
      RELEVANCE: Acute, unilateral transverse sinus occlusion during craniectomy can be
      used to increased surgical exposure to the caudal fossa of the brain without
      increased risk of increasing ICP.

PMID- 9150558
TI  - Partial resection and omentalization: a new technique for management of prostatic
      retention cysts in dogs.
AB  - OBJECTIVE: The purpose of this study was to determine the results of a new
      technique for management of prostatic retention cysts in dogs. STUDY DESIGN: A
      retrospective clinical study. ANIMALS: Eighteen client-owned dogs. METHODS: Dogs
      with prostatic retention cysts were treated by celiotomy and drainage of the
      cysts. The majority of the cyst wall was resected and residual cyst cavities were
      packed with omentum. All dogs were castrated. RESULTS: Long-term resolution of
      clinical signs was achieved in all dogs, with follow-up periods ranging from 6 to
      42 months. Five dogs developed urinary incontinence postoperatively. This
      persisted in two dogs, but was well controlled with phenylpropanolamine. In the
      remaining dogs, the incontinence was transient and resolved within 2 months of
      surgery. CONCLUSIONS: Partial cyst resection combined with omentalization and
      castration was a simple and effective means of managing prostatic retention
      cysts. The incidence of serious complications, including postoperative urinary
      incontinence, was low.

PMID- 9150559
TI  - Passive drainage versus primary closure after total ear canal ablation-lateral
      bulla osteotomy in dogs: 59 dogs (1985-1995).
AB  - OBJECTIVE: Compare passive wound drainage to primary closure of total ear canal
      ablation-lateral bulla osteotomy (TECA-LBO) in dogs. STUDY DESIGN: Retrospective
      analysis of medical records. SAMPLE POPULATION: Fifty-nine dogs with end-stage
      otitis externa or neoplasia of the external and middle ear. METHODS: Medical
      records of dogs with TECA-LBO were reviewed. Dogs were divided into postoperative
      drain and primary closure groups. Statistical analyses were performed to identify
      differences in data for signalment, preoperative treatment, duration of
      hospitalization, immediate complications, and long-term complications between
      groups. RESULTS: No significant differences were detected in signalment,
      diagnosis, and duration of medical management between groups (P > .05). Duration
      of hospitalization was greater for dogs in the drain group (P < .05). Immediate
      postoperative complications occurred in 26 of 59 dogs and included ipsilateral
      facial palsy, incision swelling, vestibular signs, premature drain removal, and
      one dog died of aspiration pneumonia. Long-term (> 6 months) complications were
      identified in 12 of 50 dogs and included dermatitis of the medial aspect of the
      pinna, chronic fistula formation, and permanent facial paralysis. No association
      between immediate or long term complications and method of closure was
      identified. CONCLUSIONS: Primary closure is an acceptable alternative in dogs
      undergoing TECA-LBO when surgical wound dead space can be managed with meticulous
      hemostasis, complete debridement of devitalized tissue, and accurate apposition
      of tissue planes.

PMID- 9150560
TI  - Clinical and radiographic evaluation of intertrochanteric osteotomy in dogs: a
      retrospective study of 18 dogs.
AB  - OBJECTIVE: To determine whether intertrochanteric osteotomy (ITO) can prevent the
      progression of degenerative joint disease (DJD) in dysplastic hip joints. STUDY
      DESIGN: The results of ITO were assessed retrospectively by using owner
      questionnaires, physical examination, and radiographic evaluation. ANIMALS:
      Eighteen client-owned dogs (29 coxofemoral joints were evaluated). METHODS:
      Lameness was scored according to a grading system. A scoring system was also
      developed to assess radiographically evident osteoarthritis on a ventrodorsal
      projection of the coxofemoral joints in extension. RESULTS: Twenty-nine ITO were
      performed in 18 dogs with varying degrees of hip dysplasia. The dogs were lame on
      19 of 29 rear limbs on physical examination before surgery. In 22 of the 29 hip
      joints, palpation caused signs of pain. The median age at the first and second
      surgical procedure was 14.5 months and 18 months, respectively. Follow-up
      evaluation was performed on average at 9.77 (FU I), 22.52 (FU II), and 47.50
      months (FU III) after surgery. Based on the owners' evaluation, there was a
      tendency toward improvement after surgery. The results of the physical
      examination at the preoperative examination and at the three follow-up
      examinations did not differ significantly. The follow-up radiographic scores
      showed significantly worse DJD than the preoperative scores. CONCLUSIONS: ITO
      does not prevent progression of DJD in the dysplastic hip. CLINICAL RELEVANCE:
      Knowledge of the long-term effects of ITO is essential for surgeons trying to
      achieve improvement in dogs with hip dysplasia.

PMID- 9150561
TI  - Results of screw/wire/polymethylmethacrylate composite fixation for acetabular
      fracture repair in 14 dogs.
AB  - OBJECTIVE: To assess the clinical results in dogs with acetabular fractures
      stabilized using a screw-wire-polymethylmethacrylate (SWP) composite fixation.
      STUDY DESIGN: A retrospective study of client-owned dogs with acetabular
      fractures. ANIMALS: Fourteen dogs ranging in age from 4 to 95 months (mean, 34 +/
      25 months; median, 25 months) and body weight from 8 to 39 kg (mean, 25 +/- 6
      kg; median, 27 kg). METHODS: Medical records and radiographs were retrospectively
      evaluated to determine location of the fracture, presence of preexisting
      degenerative joint disease, accuracy of fracture reduction and complications
      associated with surgery. Long-term results were evaluated by subjective
      assessment of lameness, elicitation of pain and/or crepitus on manipulation of
      the coxofemoral joint, measurements of pelvic limb circumference, coxofemoral
      joint goniometric measurements, and radiographic evaluation. RESULTS: Fracture
      reduction was considered anatomic in 13 dogs. At the time of the last follow-up
      evaluation (mean, 347 +/- 261 days; median, 380 days) 10 dogs were sound on the
      affected limb, three dogs had a subtle weight-bearing lameness of the affected
      limb, and the remaining dog had a consistent non-weight-bearing lameness of the
      affected limb. Mild (n = 10) or moderate (n = 1) degenerative changes of the
      affected coxofemoral joint attributed to the acetabular fracture and its repair
      were noted on the follow-up radiographs in 11 dogs. Limb circumference of the
      affected limb ranged from -8.2% to +10.8% (mean, -0.8 +/- 4.2%; median, -0.7%) of
      the contralateral limb. CONCLUSIONS: The SWP composite fixation consistently
      maintained anatomic reduction, was associated with few complications, and yielded
      satisfactory clinical results. CLINICAL RELEVANCE: The SWP composite fixation
      technique would seem to be an acceptable means of stabilizing acetabular
      fractures in dogs.

PMID- 9150562
TI  - Evaluation of percutaneous gastrostomy as a technique for permanent gastropexy.
AB  - OBJECTIVE: This study was designed to evaluate right-sided percutaneous
      endoscopic gastrostomy (PEG) as a method for creation of a permanent gastropexy.
      STUDY DESIGN: Percutaneous endoscopic gastrostomy adhesions were evaluated by
      gross examination and by mechanical testing and the results were compared with
      those obtained by conventional incisional gastropexy. ANIMALS OR SAMPLE
      POPULATION: Fourteen mixed-breed dogs. METHODS: Incisional gastropexies were
      performed on the dogs of group one (N = 7) and PEG tubes were placed in the dogs
      of group 2 (N = 7). All skin sutures (group 1) and PEG tubes (group 2) were
      removed on day 14. The animals were maintained for an additional 44 days before
      euthanasia and immediate necropsy. Gastropexy adhesions were evaluated and
      collected for biomechanical evaluation using a materials testing machine.
      RESULTS: The duration of the procedure for group 2 was less (32.86 min +/- 7.65)
      than for group 1 (56.29 min +/- 8.28). The number of complications was not
      significantly different between group 1 and group 2 (P = .103). Gastroperitoneal
      adhesions were present in 7 of 7 dogs in group 1 and 4 of 7 dogs in group 2. The
      adhesion lengths and widths were significantly lager in dogs in group 1 compared
      with those in group 2. The adhesions present in group 1 dogs sustained
      significantly greater tensile loads to failure (61.98 +/- 14.65 N), compared with
      the adhesions present in group 2 dogs (22.31 +/- 26.87 N). CONCLUSIONS: Right
      sided PEG inconsistently formed a weak gastropexy and the procedure was
      associated with a trend toward greater morbidity than incisional gastropexy.
      CLINICAL RELEVANCE: Right-sided PEG is not recommended as a means of prophylactic
      gastropexy.

PMID- 9150563
TI  - Diaphragmatic hernia repair in three young horses.
AB  - OBJECTIVE: This clinical report describes surgical correction of diaphragmatic
      hernia in three young horses. STUDY DESIGN: Retrospective investigation of
      medical records and subsequent racing performance. ANIMALS: Three young horses
      with diaphragmatic hernia. RESULTS: Three young horses with signs of abdominal
      pain had diaphragmatic hernia causing small intestinal strangulation. The
      strangulated small intestine was resected and an end-to-end jejuno-jejunal (two
      horses) or a side-to-side jejuno-cecal anastomosis (one horse) was performed.
      Diaphragmatic hernias were closed with a continuous suture pattern. All horses
      recovered and raced. No difference in race records was found between the subject
      horses and their siblings. One subject horse died of colic at 5 years of age, but
      the cause of the colic was undetermined. The remaining two horses are in use as
      broodmares and have produced multiple foals without recurrence of signs of
      diaphragmatic hernia. CONCLUSIONS: Diaphragmatic hernias can be repaired in
      horses. These horses can achieve race records similar to their siblings and can
      produce foals without recurrence of signs of diaphragmatic hernia.

PMID- 9150564
TI  - Anesthesia in sheep with propofol or with xylazine-ketamine followed by
      halothane.
AB  - OBJECTIVE: This study evaluates the clinical usefulness and anesthetic effect of
      propofol, and compares these effects with those of xylazine-ketamine-halothane
      anesthesia in sheep. STUDY DESIGN: Prospective, randomized, clinical trial.
      ANIMALS OR SAMPLE POPULATION: Fourteen healthy adult male sheep. METHODS: Sheep
      were randomly assigned to two different drug regimens: (1) Bolus injection of
      propofol (3 mg/kg, intravenously [i.v.]) followed by continuous intravenous
      infusion and (2) xylazine (0.11 mg/kg, i.v.) and ketamine (2.2 mg/kg, i.v.) for
      induction followed by halothane anesthesia. Heart rate, respiratory rate, and
      arterial blood pressures were monitored during anesthesia. Venous blood samples
      were collected for blood gas analysis. Quality of induction and recovery were
      also recorded. RESULTS: The average dose of propofol used to induce and maintain
      anesthesia was 6.63 +/- 2.06 mg/kg and 29.3 +/- 11.7 mg/kg/hr (0.49 +/- 0.20
      mg/kg/min), respectively. The duration of propofol anesthesia was 45.3 +/- 13.2
      minutes and recovery to standing occurred in 14.7 +/- 5.7 minutes. Sheep
      receiving xylazine-ketamine-halothane were anesthetized for 35.9 +/- 4.0 minutes
      and recovery to standing occurred within 28.5 +/- 7.5 minutes. Sheep anesthetized
      with propofol had a significantly higher heart rate, diastolic blood pressure and
      Pvo2, and a lower Pvco2 at 30 minutes and lower BE at 15 and 30 minutes than
      sheep anesthetized with xylazine-ketamine-halothane. CONCLUSIONS: Propofol
      anesthesia was characterized by a smooth induction, effective surgical anesthesia
      and rapid recovery which was comparable to anesthesia with xylazine-ketamine
      halothane. CLINICAL RELEVANCE: Propofol may be indicated in situations when it is
      desirable to maintain anesthesia with an intravenous infusion followed by a rapid
      recovery in healthy sheep.

PMID- 9150565
TI  - Origin of the biologically important elements.
AB  - The chemical elements most widely distributed in terrestrial living creatures are
      the ones (apart from inert helium and neon) that are commonest in the Universe-
      hydrogen, oxygen, carbon, and nitrogen. A chemically different Universe would
      clearly have different biology, if any. We explore here the nuclear processes in
      stars, the early Universe, and elsewhere that have produced these common
      elements, and, while we are at it, also encounter the production of lithium,
      gold, uranium, and other elements of sociological, if not biological, importance.
      The relevant processes are, for the most part, well understood. Much less well
      understood is the overall history of chemical evolution of the Galaxy, from pure
      hydrogen and helium to the mix of elements we see today. One implication is that
      we cannot do a very good job of estimating how many stars and which ones might be
      orbited by habitable planets.

PMID- 9150566
TI  - Circumstellar and interstellar synthesis of organic molecules.
AB  - We review the formation and evolution of complex circumstellar and interstellar
      molecules. A number of promising chemical routes are discussed which may lead to
      the formation of polycyclic aromatic hydrocarbon molecules, fullerenes, and
      unsaturated hydrocarbon chains in the outflows from stars. Some of the problems
      with these chemical schemes are pointed out as well. We also review the role of
      grains in the formation of complex molecules in interstellar molecular clouds.
      This starts with the formation of simple molecules in an ice grain mantle. UV
      photolysis and/or thermal polymerization can convert some of these simple
      molecules into more complex polymeric structures. Some of these species may be
      released to the gas phase, particularly in the warm regions around newly formed
      stars. Methanol and formaldehyde seem to play an important role in this drive
      towards molecular complexity and their chemistry is traced in some detail.

PMID- 9150567
TI  - Detection of organic matter in interstellar grains.
AB  - Star formation and the subsequent evolution of planetary systems occurs in dense
      molecular clouds, which are comprised, in part, of interstellar dust grains
      gathered from the diffuse interstellar medium (DISM). Radio observations of the
      interstellar medium reveal the presence of organic molecules in the gas phase and
      infrared observational studies provide details concerning the solid-state
      features in dust grains. In particular, a series of absorption bands have been
      observed near 3.4 microns (approximately 2940 cm-1) towards bright infrared
      objects which are seen through large column densities of interstellar dust.
      Comparisons of organic residues, produced under a variety of laboratory
      conditions, to the diffuse interstellar medium observations have shown that
      aliphatic hydrocarbon grains are responsible for the spectral absorption features
      observed near 3.4 microns (approximately 2940 cm-1). These hydrocarbons appear to
      carry the -CH2- and -CH3 functional groups in the abundance ratio CH2/CH3
      approximately 2.5, and the amount of carbon tied up in this component is greater
      than 4% of the cosmic carbon available. On a galactic scale, the strength of the
      3.4 microns band does not scale linearly with visual extinction, but instead
      increases more rapidly for objects near the Galactic Center. A similar trend is
      noted in the strength of the Si-O absorption band near 9.7 microns. The similar
      behavior of the C-H and Si-O stretching bands suggests that these two components
      may be coupled, perhaps in the form of grains with silicate cores and refractory
      organic mantles. The ubiquity of the hydrocarbon features seen in the near
      infrared near 3.4 microns throughout out Galaxy and in other galaxies
      demonstrates the widespread availability of such material for incorporation into
      the many newly forming planetary systems. The similarity of the 3.4 microns
      features in any organic material with aliphatic hydrocarbons underscores the need
      for complete astronomical observational coverage in the 2-30 microns region, of
      lines of sight which sample dust in both dense and diffuse interstellar clouds,
      in order to uniquely specify the composition of interstellar organics. This paper
      reviews the information available from ground-based observations, although
      currently the Infrared Satellite Observatory is adding to our body of knowledge
      on this subject by providing more extensive wavelength coverage. The Murchison
      carbonaceous meteorite has also been used as an analog to the interstellar
      observations and has revealed a striking similarity between the light
      hydrocarbons in the meteorite and the ISM; therefore this review includes
      comparisons with the meteoritic analog as well as with relevant laboratory
      residues. Fundamental to the evolution of the biogenic molecules, to the process
      of planetary system formation, and perhaps to the origin of life, is the
      connection between the organic material found in the interstellar medium and that
      incorporated in the most primitive solar system bodies.

PMID- 9150568
TI  - The nature and evolution of interstellar ices.
AB  - The evolution of icy grain mantles is governed by the environment in which they
      exist. This review presents an overview of the study of the molecules that make
      up the mantles and discusses their relevance to the origin of life. Models
      predict two phases of mantle growth during cloud collapse: simple polar and
      nonpolar molecules dominate the mantle layers at early and late times,
      respectively (Section 1). The effect of processing on grain mantle composition
      and the connection between organics in grain mantles and prebiotic chemistry is
      introduced. Section 2 describes how infrared spectroscopy of dense cloud sources,
      combined with theoretical models and laboratory data, gives us information on the
      composition and abundance of the ices in varying regions. The observed features
      and how they are used as diagnostics of mantle evolution are discussed in Section
      3. This section also discusses the importance of these molecules to prebiotic
      chemistry. Section 4 compares grain mantle composition in different low-mass star
      forming regions, which best represent the solar birthplace. The final section
      (Section 5) summarizes the information presented, emphasizing the link between
      the study of interstellar dust and the origin of life.

PMID- 9150569
TI  - Interstellar ices studied with the Infrared Space Observatory.
AB  - The Infrared Space Observatory (ISO) was launched by the European Space Agency on
      17 November 1995. The availability of spectra from the Short Wavelength
      Spectrometer (SWS) on ISO is a landmark in the study of interstellar ices and
      organics; they provide a wealth of data in the 2-20 microns region of the
      spectrum covering the principal solid state resonances of condensed matter in
      interstellar clouds. We thus have the opportunity to study many species likely to
      be relevant to the inventory of CNO-bearing interstellar material present at the
      formation of our own and other planetary systems. This paper presents a brief
      overview of what has been learned from the data available so far. A comparison is
      made between the compositions of ices in molecular clouds, protostellar
      condensations and comets. Key areas of uncertainty are highlighted as a basis for
      future research.

PMID- 9150570
TI  - The search for interstellar glycine.
AB  - Millimeter arrays can be used to identify hot young molecular cores which contain
      large, highly saturated interstellar molecules, including biomolecules. These
      cores are prime locations for searching for interstellar glycine. The current
      status of the interstellar glycine search is discussed.

PMID- 9150571
TI  - The origin of low mass stars.
AB  - Recent evidence indicates that most low mass stars in the Galaxy (< 5 M [symbol:
      see text]) form alongside massive stars in clusters embedded in giant molecular
      clouds. Once their parental gas is removed, the fate of these clusters is to
      disperse and blend into the field population of the galactic disk. The
      distribution of stellar masses in the solar neighborhood, called the Initial Mass
      Function, is discussed in the context of the origin of low mass stars. Arguments
      based on the production rate of field stars are presented that point to giant
      molecular clouds as the primary birth sites for low mass stars. The role of
      observations of molecular clouds at millimeter and infrared wavelengths in
      confirming this picture is reviewed. Millimeter-wave observations have revealed
      that molecular clouds consist of low-density gas interspersed with high-density
      cores. Near-infrared images of these clouds indicate that stars form
      preferentially in these cores, with the number of young stars roughly scaling
      with the mass of the core. Molecular-line and near-infrared observations which
      characterize star formation in the nearest giant molecular cloud complex in Orion
      are presented. The implications for the Sun forming in a cluster environment are
      briefly discussed.

PMID- 9150572
TI  - Analogs of the early solar system.
AB  - Within the last few decades, the existence of protoplanetary disks has been
      inferred on the basis of emission from T Tauri stars that does not arise from a
      stellar photosphere. More recently, high-resolution interferometric techniques
      have resolved the dust continuum emission, and millimeter arrays have imaged
      circumstellar molecular gas. These measurements corroborate the disk
      interpretation; many T Tauri stars are surrounded by centrifugally supported
      circumstellar disks with radial sizes of order 100 AU. Further proof issues from
      Hubble Space Telescope images of disks that are illuminated externally. The
      morphology of circumstellar dust is revealed in striking detail and affirms the
      prevalence and dimensions of disks imaged at longer wavelengths. The fate of
      circumstellar material around young stars must be understood in order to discern
      the degree to which these disks are proto-planetary. Observational studies of
      circumstellar disks which are in the beginning of a dispersal phase are
      challenging and place great demands on astronomical techniques. Nevertheless, the
      connection between disks and the formation of extra-solar planets is supported by
      increasing circumstantial evidence. Optically thin dust continuum emission
      persists in T Tauri stars and is detected around some young main sequence stars.
      Since the dust is subject to rapid dispersal by radiation pressure and Poynting
      Robertson drag, some mechanism of replenishment is required. Disks around nearby
      young main sequence stars show evidence for inner voids and disk asymmetries that
      should also disappear on short timescales. The presence of large orbiting bodies
      which collide and interact with the resulting debris can explain both the
      persistence of optically thin dust and the maintenance of otherwise-ephemeral
      dynamical features. Together with recent detections of extra-solar planets, these
      observations lend some support to the hypothesis that circumstellar disks
      commonly give birth to planetary systems.

PMID- 9150573
TI  - The early solar system.
AB  - Life arose on an early Earth which was the product to the conditions present, and
      processes operating, during formation of the solar system. The formation and
      early state of the solar system are reviewed in order to better understand the
      nature of the early Earth, and to constrain the conditions present during the
      origin and early evolution of life on this planet.

PMID- 9150574
TI  - Physics and chemistry of the solar nebula.
AB  - The solar system is thought to have begun in a flattened disk of gas and dust
      referred to traditionally as the solar nebula. Such a construct seems to be a
      natural product of the collapse of dense parts of giant molecular clouds, the
      vast star-forming regions that pepper the Milky Way and other galaxies.
      Gravitational, magnetic and thermal forces within the solar nebula forced a
      gradual evolution of mass toward the center (where the sun formed) and angular
      momentum (borne by a small fraction of the mass) toward the outer more distant
      regions of the disk. This evolution was accompanied by heating and a strong
      temperature contrast from the hot, inner regions to the cold, more remote parts
      of the disk. The resulting chemistry in the disk determined the initial
      distribution of organic matter in the planets; most of the reduced carbon
      species, in condensed form, were located beyond the asteroid belt (the 'outer'
      solar system). The Earth could have received much of its inventory of pre
      biological material from comets and other icy fragments of the process of
      planetary formation in the outer solar system.

PMID- 9150575
TI  - Chemical evolution on Titan: comparisons to the prebiotic earth.
AB  - Models for the origin of Titan's atmosphere, the processing of the atmosphere and
      surface and its exobiological role are reviewed. Titan has gained widespread
      acceptance in the origin of life field as a model for the types of evolutionary
      processes that could have occurred on prebiotic Earth. Both Titan and Earth
      possess significant atmospheres (> or = 1 atm) composed mainly of molecular
      nitrogen with smaller amounts of more reactive species. Both of these atmospheres
      are processed primarily by solar ultraviolet light with high energy particles
      interactions contributing to a lesser extent. The products of these reactions
      condense or are dissolved in other atmospheric species (aerosols/clouds) and fall
      to the surface. There these products may have been further processed on Titan and
      the primitive Earth by impacting comets and meteorites. While the low
      temperatures on Titan (approximately 72-180 K) preclude the presence of permanent
      liquid water on the surface, it has been suggested that tectonic activity or
      impacts by meteors and comets could produce liquid water pools on the surface for
      thousands of years. Hydrolysis and oligomerization reactions in these pools might
      form chemicals of prebiological significance. Other direct comparisons between
      the conditions on present day Titan and those proposed for prebiotic Earth are
      also presented.

PMID- 9150576
TI  - Is extraterrestrial organic matter relevant to the origin of life on Earth?
AB  - I review the relative importance of internal and external sources of prebiotic
      molecules on Earth at the time of life's origin approximately 3.7 Gyr ago. The
      efficiency of synthesis in the Earth's atmosphere was critically dependent on its
      oxidation state. If the early atmosphere was non-reducing and CO2-dominated,
      external delivery might have been the dominant source. Interplanetary dust grains
      and micrometeorites currently deliver carbonaceous matter to the Earth's surface
      at a rate of approximately 3 x 10(5) kg/yr (equivalent to a biomass in
      approximately 2 Gyr), but this may have been as high as 5 x 10(7) kg/yr (a
      biomass in only approximately 10 Myr) during the epoch of late bombardment. Much
      of the incoming material is in the form of chemically inactive kerogens and
      amorphous carbon; but if the Earth once had a dense (approximately 10-bar)
      atmosphere, small comets rich in a variety of prebiotic molecules may have been
      sufficiently air-braked to land non-destructively. Lingering uncertainties
      regarding the impact history of the Earth and the density and composition of its
      early atmosphere limit our ability to draw firm conclusions.

PMID- 9150577
TI  - The search for life on Mars.
AB  - Mars appears to have no life on its surface today. However, the presence of
      fluvial features provides evidence that liquid water was once present on the
      martian surface. By analogy with Earth, life may have originated on Mars early in
      its history, possibly during the end of the late heavy bombardment. Analysis of
      the one meteorite from Mars which dates to this early time appears to contain
      evidence of this early environment and possibly life. As the climate cooled and
      liquid water became unavailable, life would have eventually died out. The cold
      deserts of Antarctica provide a glimpse of what martian ecosystems might have
      been like as conditions worsened. The search for fossil evidence of past life on
      Mars may provide the first direct indication of life beyond Earth.

PMID- 9150578
TI  - Habitable zones around low mass stars and the search for extraterrestrial life.
AB  - Habitable planets are likely to exist around stars not too different from the Sun
      if current theories about terrestrial climate evolution are correct. Some of
      these planets may have evolved life, and some of the inhabited planets may have
      evolved O2-rich atmospheres. Such atmospheres could be detected spectroscopically
      on planets around nearby stars using a space-based interferometer to search for
      the 9.6 micron band of O3. Planets with O2-rich atmospheres that lie within the
      habitable zone around their parent star are, in all probability, inhabited.

PMID- 9150579
TI  - When exceptions prove the rule: how extremity of deviance determines the impact
      of deviant examples on stereotypes.
AB  - The authors examined how the extent to which counterstereotypic individuals
      deviate from perceivers' stereotypes affects their impact on these stereotypes
      and found that extremely deviant group members provoke less stereotype
      assimilation than do moderately deviant ones. Extremely deviant examples can even
      provoke boomerang effects, that is, enhance the very stereotype that they
      violate. When participants whose prior stereotype were moderate or extreme were
      exposed to moderately or extremely deviant examples, the deviant examples' impact
      on stereotypes depended both on their extremity and on the extremity of
      perceivers' prior stereotypes. Boomerang effects were obtained only for extreme
      stereotype participants exposed to extremely deviant examples and were mediated
      by perceptions of the typicality of the deviant examples. Open-ended explanations
      revealed that the atypicality of extremely deviant examples was used as grounds
      for dismissing them.

PMID- 9150580
TI  - A new look at defensive projection: thought suppression, accessibility, and
      biased person perception.
AB  - It has long been assumed that people perceive in others qualities that they wish
      to deny in themselves, but empirical evidence for defensive projection is limited
      and controversial. A new model for projection is presented in this article.
      People might try to actively suppress thoughts about the possibility that they
      have undesirable personality traits, but it was hypothesized that this response
      to threat ultimately causes thoughts about the unwanted traits to become
      chronically accessible. As a result, those trait concepts will be used to
      interpret others' behavior. Studies 1-4 showed that those people who both avoid
      thinking about having threatening personality traits and deny possessing them
      (repressors) also readily infer those traits from others' behavior. Studies 5-6
      provided experimental support for the model. Unfavorable traits were attributed
      to participants, who, when they were asked or predisposed to not think about the
      traits, subsequently projected them onto someone else.

PMID- 9150581
TI  - Mood and the correction of positive versus negative stereotypes.
AB  - The present research examined the effects of sadness on the correction of social
      stereotypes. Participants who either were not induced to feel sad were asked to
      form an impression of a single individual who belonged to a group that had either
      stereotypically positive or negative implications. Experiments 1 and 2 showed
      that sad people corrected for their negative, but not for their positive
      stereotypes. Experiment 3 demonstrated that this asymmetry was not due to
      stereotype valence per se but to whether the stereotype was perceived as an
      inappropriate basis for judgment. A model is presented that suggests that sad
      people do not simply ignore category-based information, but rather correct for
      their stereotypes only when they are perceived as inappropriate, which tends to
      be more often the case if the stereotype is negative than if it is positive. The
      implications of the present results for 4 extant models of mood and information
      processing are discussed.

PMID- 9150582
TI  - Emotional state and the use of stimulus dimensions in judgment.
AB  - Previous studies have demonstrated that, when they are emotional, individuals are
      more likely to attend to emotional stimuli. However, such work has not
      established that individuals attend to the emotional dimensions of complex
      stimuli or that such changes in focus of attention judgments. In the present
      experiments a multidimensional scaling analysis was used to assess the weights
      that happy, sad, and neutral-emotion participants gave to emotional and
      nonemotional dimensions of face stimuli in judgments of similarity. Compared to
      neutral-emotion participants, those in emotional states gave more weight to the
      emotional dimension of the faces, less weight to other face dimensions, and rated
      pairs of faces that expressed the same emotion as more similar. Emotion-congruent
      dimension use was also observed in one experiment. Results are discussed with
      respect to emotional response categories (P.M. Niedenthal & J.B. Halberstadt,
      1995), the tendency for stimuli to cohere as categories on the basis of the
      emotional response they elicit in the perceiver.

PMID- 9150583
TI  - How do I judge my outcome when I do not know the outcome of others? The
      psychology of the fair process effect.
AB  - On the basis of fairness heuristic theory, the authors provide an explanation of
      the frequently replicated fair process effect (the finding that perceived
      procedural fairness positively affects how people react to outcomes). The authors
      argue that, in many situations, people may find it difficult to assess whether
      their outcome is fair or unfair and satisfying or unsatisfying because they only
      have information about their own outcome and they do not know the outcomes of
      others and that, in these situations, people use the fairness of the procedure as
      a heuristic substitute to assess how to judge their outcome. The results of 2
      experiments corroborate the authors' line of reasoning. Findings are discussed in
      terms of recent developments toward an integration of the procedural and
      distributive justice domains.

PMID- 9150584
TI  - Brief encounters ending in estrangement: motivated language use and interpersonal
      rapport in the question-answer paradigm.
AB  - Three experiments explored need-for-for-closure effects in the question-answer
      paradigm. In experiment 1, participants under high (vs. low) need for closure
      selected more abstract interview questions. In Experiments 2 and 3, such
      questions elicited more abstract answers--answers that casually implicated the
      object (vs. the subject) of the sentence and that prompted a less positive
      perceived rapport between the interviewer and the interviewee. These findings are
      discussed in reference to the role of motivation in language and the possible
      interpersonal consequences of motivated language use.

PMID- 9150585
TI  - Self-interest and fairness in problems of resource allocation: allocators versus
      recipients.
AB  - Two studies explored the tension between self-interest and the equality norm in
      problems of resource allocation. Study 1 presented graduate business students
      with a hypothetical task requiring them to make a series of managerial decisions.
      On learning the outcome of those decisions, they were asked to divide a bonus
      pool between self and a rival manager (who had opted for very different decisions
      and achieved either the same results as self on 2 criteria or a better result on
      1 criterion and a worse result on the other criterion). Study 2 required Stanford
      and San Jose State undergraduates to consider the division of a hypothetical
      scholarship fund between candidates from their 2 schools. Data from both studies
      contrasted the apparent evenhandedness and lack of self-interest manifested by
      allocators with the self-serving responses of evaluators. Furthermore, when faced
      with different claims, participants were inclined to justify an unequal
      allocation of resources--provided that they, or a representative of their group,
      received the larger share--that few personally would have recommended, demanded,
      or imposed.

PMID- 9150586
TI  - Neuroticism, marital interaction, and the trajectory of marital satisfaction.
AB  - Theories of how initially satisfied marriages deteriorate or remain stable over
      time have been limited by a failure to distinguish between key facets of change.
      The present study defines the trajectory of marital satisfaction in terms of 2
      separate parameters--(a) the initial level of satisfaction and (b) the rate of
      change in satisfaction over time--and seeks to estimate unique effects on each of
      these parameters with variables derived from intrapersonal and interpersonal
      models of marriage. Sixty newlywed couples completed measures of neuroticism,
      were observed during a marital interaction and provided reports of marital
      satisfaction every 6 months for 4 years. Neuroticism was associated with initial
      levels of marital satisfaction but had no additional effects on rates of change.
      Behavior during marital interaction predicted rates of change in marital
      satisfaction but was not associated with initial levels.

PMID- 9150587
TI  - Motivated language use in intergroup contexts: need-for-closure effects on the
      linguistic intergroup bias.
AB  - Two experiments examined the impact of the motivation for cognitive closure on
      the abstractness of linguistic communications in intergroup contexts.
      Participants described positive and negative behaviors attributed to either an in
      group or an out-group member. Individuals high (vs. low) in need for closure
      exhibited greater linguistic abstraction when describing positive behaviors of in
      group members and negative behaviors of out-group members. These differences
      disappeared for descriptions of negative behaviors of out-group members. The
      discussion relates these results to the interface of motivation, language, and
      social cognition.

PMID- 9150588
TI  - Terror management and cognitive-experiential self-theory: evidence that terror
      management occurs in the experiential system.
AB  - The authors hypothesized, on the basis of terror management theory and cognitive
      experiential self-theory, that participants in an experiential mode of thinking
      would respond to mortality salience with increased worldview defense and
      increased accessibility of death-related thoughts, whereas participants in a
      rational mode would not. Results from 3 studies provided convergent evidence that
      when participants were in an experiential mode, mortality salience produced the
      typical worldview defense effect, but when participants were in a rational mode
      it did not. Study 4 revealed that mortality salience also led to a delayed
      increase in the accessibility of death-related thoughts only when participants
      were in an experiential mode. These results supported the notion that worldwide
      defense is intensified only if individuals are in an experiential mode when
      considering their mortality. Discussion focuses on implications for understanding
      terror management processes.

PMID- 9150589
TI  - Predicting women's well-being in midlife: the importance of personality
      development and social role involvements.
AB  - Theories of adult development suggest that both personality and social roles are
      sources of adult well-being, but most research has examined only social roles. An
      integrated model was used, including personality, number of roles, and role
      quality, to predict well-being in 2 longitudinal studies of college-educated
      women. Results for both samples indicated that role quality and personality
      development were important components of the path to well-being, whereas number
      of roles, occupied was important mainly in early adulthood. Moreover, the results
      provided support for E. Erikson's (1968) notion of the importance of the
      sequencing of personality development for later well-being. Path analyses
      indicated that engagement in multiple roles during early adulthood facilitated
      the development of identity, which predicted generativity and role quality, which
      in turn predicted well-being.

PMID- 9150590
TI  - Self-determination and persistence in a real-life setting: toward a motivational
      model of high school dropout.
AB  - The purpose of this study was to propose and test a motivational model of high
      school dropout. The model posits that teachers, parents, and the school
      administration's behaviors towards students influence students' perceptions of
      competence and autonomy. The less autonomy supportive the social agents'
      behaviors are, the less positive the students' perceptions of competence and
      autonomy. In turn, the less positive students' perceptions are, the lower their
      level of self-determined school motivation are. Finally, low levels of self
      determined motivation lead students to develop intentions to drop out of high
      school, which are later implemented, leading to actual dropout behavior. This
      model was tested with high school students (N = 4,537) by means of a prospective
      design. Results from analyses of variance and a structural equation modeling
      analysis (with LISREL) were found to support the model for all participants and
      for each gender separately.

PMID- 9150591
TI  - Adult attachment style and information processing: individual differences in
      curiosity and cognitive closure.
AB  - Five studies examined the association between adult attachment style and
      information processing. Studies 1-2 focused on information search (curiosity
      related beliefs and behaviors). Studies 3-5 focused on the integration of new
      information within cognitive structures; namely, the level of cognitive closure
      and its expressions in social judgements. Secure and anxious-ambivalent persons
      described themselves as more curious and held more positive attitudes toward
      curiosity than did avoidant persons. Time competition between information search
      and social interaction increased information search among avoidant persons, but
      decreased it among anxious-ambivalent persons. Finally, secure persons reported
      less preference for cognitive closure and were more likely to rely on new
      information in making social judgements than avoidant and anxious-ambivalent
      persons. The theoretical implications of the link between attachment and
      information processing are discussed.

PMID- 9150592
TI  - Characterization of in planta-induced rust genes isolated from a haustorium
      specific cDNA library.
AB  - Rust fungi are plant parasites that depend on living host tissue for growth. For
      invasion of leaves, dikaryotic urediospores differentiate germ tubes and
      infection structures that penetrate through stomata. Biotrophic growth occurs by
      intercellular mycelia that form haustoria within host cells. A cDNA library was
      constructed from haustoria isolated from broad bean leaves infected by Uromyces
      fabae. Differential screening revealed that a high proportion (19%) of the
      haustorial cDNAs are specifically expressed in planta but are not expressed, or
      are much weaker, in germlings or infection structures produced in vitro. A total
      of 31 different in planta-induced genes (PIGs) were identified. Some of the PIGs
      are highly expressed in haustoria. The PIGs are single or low copy number genes
      in the rust genome. A variety of developmentally regulated expression patterns of
      PIG mRNAs were observed. Sequence analysis of PIG cDNAs revealed similarities to
      genes encoding proteins involved in amino acid transport, thiamine biosynthesis,
      short-chain dehydrogenases, metallothioneins, cytochrome P-450 monooxygenases,
      and peptidyl-prolyl isomerases.

PMID- 9150593
TI  - A putative amino acid transporter is specifically expressed in haustoria of the
      rust fungus Uromyces fabae.
AB  - A cDNA library constructed from haustoria of the rust fungus Uromyces fabae was
      screened for clones that are differentially expressed in haustoria. One family of
      cDNAs (in planta-induced gene 2 [PIG2] was isolated and found to encode a protein
      with high homologies to fungal amino acid transporters. A cDNA clone containing
      the complete coding region of PIG2 and the corresponding genomic clone were
      isolated and sequenced, revealing the presence of 17 introns in the PIG2 gene.
      Expression of PIG2 mRNA appeared to be restricted to haustoria. With antibodies
      raised against synthetic peptides, the PIG2-encoded protein was found in
      membranes fractions of isolated haustoria but not of germinated rust spores. With
      immunofluorescence microscopy, the putative amino acid transporter was localized
      to plasma membranes of the haustorial bodies, but not detected in the haustorial
      neck, haustorial mother cells, or intercellular fungal hyphae growing within
      infected leaf tissue. These data present for the first time molecular evidence
      that the rust haustorium plays a special role in the uptake of nutrients from an
      infected host cell.

PMID- 9150594
TI  - The melanin biosynthesis genes of Alternaria alternata can restore pathogenicity
      of the melanin-deficient mutants of Magnaporthe grisea.
AB  - The phytopathogenic fungi Magnaporthe grisea and Alternaria alternata produce
      melanin via the polyketide biosynthesis, and both fungi form melanized colonies.
      However, the site of melanin deposition and the role of melanin in pathogenicity
      differ between these two fungi. M. grisea accumulates melanin in appressoria, and
      their melanization is essential for host penetration. On the other hand, A.
      alternata produces colorless appressoria, and melanin is not relevant to host
      penetration. We examined whether the melanin biosynthesis genes of A. alternata
      could complement the melanin-deficient mutations of M. grisea. Melanin-deficient,
      nonpathogenic mutants of M. grisea, albino (Alb-), rosy (Rsy-), and buff (Buf-),
      were successfully transformed with a cosmid clone pMRB1 that carries melanin
      biosynthesis genes ALM, BRM1, and BRM2 of A. alternata. This transformation
      restored the melanin synthesis of the Alb- and Buf- mutants, but not that of the
      Rsy- mutant. The melanin-restored transformants regained mycelial melanization,
      appressorium melanization, and pathogenicity to rice. Further, transformation of
      Alb- and Buf- mutants with subcloned ALM and BRM2 genes, respectively, also
      produced melanin-restored transformants. These results indicate that the
      Alternaria genes ALM and BRM2 can restore pathogenicity to the mutants Alb- and
      Buf-, respectively, due to their function during appressorium development in M.
      grisea.

PMID- 9150595
TI  - Molecular characterization and expression of the Erwinia carotovora hrpNEcc gene,
      which encodes an elicitor of the hypersensitive reaction.
AB  - The nucleotide sequence of hrpNEcc DNA, cloned from Erwinia carotovora subsp.
      carotovora strain Ecc71, reveals a coding region of 1,068 bp which matches the
      size of hrpNEcc transcripts. hrpNEcc is predicted to encode a glycine-rich
      protein of approximately 36 kDa. Like the elicitors of the hypersensitive
      reaction (HR) produced by E. chrysanthemi (HarpinEch) and E. amylovora
      (HarpinEa), the deduced 36-kDa protein does not possess a typical signal
      sequence, but it contains a putative membrane-spanning domain. In Escherichia
      coli strains overexpressing hrpNEcc, the 36-kDa protein has been identified as
      the hrpNEcc product by Western blot analysis using anti-HarpinEch antibodies. The
      36-kDa protein fractionated from E. coli elicits the HR in tobacco leaves.
      Moreover, a HrpN- and RsmA- double mutant (RsmA = regulator of secondary
      metabolites) does not produce this 36-kDa protein or elicit the HR, although this
      strain, like the RsmA- and HrpN+ bacteria, overproduces extracellular enzymes and
      macerates celery petioles. These observations demonstrate that hrpNEcc encodes
      the elicitor of the HR, designated HarpinEcc. The levels of hrpNEcc transcripts
      are affected in both RsmA+ and RsmA- strains by media composition and carbon
      sources, although the mRNA levels are substantially higher in the RsmA- strains.
      The expression of hrpNEcc in Ecc71 is cell density dependent and is activated by
      the quorum-sensing signal, N-(3-oxohexanoyl)-L-homoserine lactone (OHL). By
      contrast, hrpNEcc expression in an RsmA- strain is independent of cell density,
      and substantial expression occurs in the absence of OHL. The effects of cultural
      conditions and the occurrence of putative cis-acting sequences, such as consensus
      sigma 54 promoters and an hrp promoter upstream of the transcriptional start
      site, indicate that the production of HarpinEcc in wild-type RsmA+ E. carotovora
      subsp. carotovora is tightly regulated. These observations, taken along with the
      finding that the HR is caused by RsmA- mutants but not by RsmA+ strains (Cui et
      al., 1996, Mol. Plant-Microbe Interact. 9:565-573), strongly support the idea
      that the inability of the wild-type pectolytic E. carotovora subsp. carotovora to
      elicit the HR is due to the lack of a significant level of HarpinEcc production.

PMID- 9150596
TI  - Two separate regions in the genome of the tobacco etch virus contain determinants
      of the wilting response of Tabasco pepper.
AB  - Infection of Tabasco pepper by the tobacco etch virus (TEV) typically causes
      wilting associated with root necrosis. However, a strain of TEV, designated TEV
      nonwilting (TEV NW), is able to infect Tabasco pepper plants but does not cause
      wilting. In order to locate the genetic determinants responsible for the wilting
      response, a full-length cDNA clone of TEV NW from which infectious transcripts
      can be derived was made. A number of chimeric constructs were prepared by
      substituting cDNA fragments between TEV HAT (which causes wilting) and TEV NW
      clones. This approach was used to identify two wilting determinants in TEV HAT:
      one encompasses the 3' one-third of the P3 encoding region; the other spans the
      3' end of the CI, the 6-kDa protein, and the 5' end of the VPg-NIa coding
      regions. Substitutions of both these TEV NW fragments into TEV HAT resulted in
      infection but not wilting of Tabasco pepper, while the replacement of either of
      the fragments alone did not alter the wilting response. This indicates that both
      TEV NW regions contain determinants necessary but not sufficient to alter the
      wilting response and that both must be present in order to avoid the wilting
      response. There was no difference between the in vitro transcription-translation
      products derived from constructs containing these regions from TEV HAT and TEV
      NW.

PMID- 9150597
TI  - hrpf of Xanthomonas campestris pv. vesicatoria encodes an 87-kDa protein with
      homology to NoIX of Rhizobium fredii.
AB  - The gram-negative bacterium Xanthomonas campestris pv. vesicatoria is the causal
      agent of bacterial spot disease on pepper and tomato plants. The main hrp
      (hypersensitive reaction and pathogenicity) gene cluster in X. campestris pv.
      vesicatoria spans a 23-kb chromosomal region, comprising six complementation
      groups designated hrpA to hrpF. Analysis of the hrpF locus revealed a single open
      reading frame encoding HrpF (86.4 kDa). HrpF is predominantly hydrophilic, and
      contains two hydrophobic domains in the C terminus. An interesting feature is the
      presence of two imperfect direct repeats in the N-terminal region. Deletion
      studies showed that one repeat is sufficient for function. Epitope tagging of
      HrpF allowed detection of the protein in X. campestris pv. vesicatoria.
      Subcellular localization studies suggest that HrpF is both in the soluble
      fraction and in the inner membrane. Interestingly, HrpF is 48% identical (67%
      similar) to the Rhizobium fredii NoIX protein that is part of the host
      specificity locus. Since several Hrp proteins are believed to be components of
      the types of III hrp protein secretion apparatus, allowing export of proteins
      essential for the interaction with the plant, the possible role of hrpF and NoIX
      in secretion is discussed.

PMID- 9150598
TI  - New Rhizobium leguminosarum flavonoid-induced proteins revealed by proteome
      analysis of differentially displayed proteins.
AB  - Proteome analysis was used to establish the first two-dimensional protein map of
      Rhizobium. R. leguminosarum bv. trifolii strain ANU843 was grown in defined
      medium in the presence and absence of the flavonoid 7,4'-dihydroxyflavone. Over
      1,700 constitutive proteins were resolved, representing about 30% of the
      estimated genomic output. Proteome analysis of flavonoid-treated cells was done
      to reveal differentially displayed proteins. The results showed that while the
      global expression pattern of proteins was largely unaltered by the treatment,
      four inducible proteins were observed. The four inducible proteins and 20
      constitutively expressed proteins were subjected to sequence analysis to provide
      internal standards for the construction of a two-dimensional Rhizobium protein
      data base. The identity of 12 proteins, including NodE and NodB, was established.
      NodE was present throughout the growth of the cells but was diminished in amount
      in stationary phase cells whereas NodB was not detected in the later stages of
      growth. Two of the induced proteins sequenced did not match any known nodulation
      gene product, with one of these being present in mid-late log and stationary
      phase cells and possessing four consecutive His residues at the N-terminal
      sequencing was successful with 100 to 200 fmol of protein. Proteome analysis
      provides a sensitive new tool to examine plant-microbe interactions.

PMID- 9150599
TI  - A single amino acid substitution in the antimicrobial defense protein cecropin B
      is associated with diminished degradation by leaf intercellular fluid.
AB  - Degradation is one of several factors that may affect the level of accumulation
      of transgene products in plants. In plants engineered to secrete antimicrobial
      proteins to the intercellular compartment of leaves, the degenerative activity of
      proteases residing in leaf intercellular fluid (IF) could be critical to
      achieving the expected transgene function. We synthesized a structural analogue
      (MB39) of the antibacterial protein cecropin B and compared the susceptibility of
      both proteins to degradation in vitro by IF extracted from leaves of various
      crops. The half-life of the two proteins in the various IF extracts ranged from 3
      min to 25.5 h, with the analogue MB39 displaying the longer half-life in IF from
      nine of 10 species. Overall, the half-life of MB39 averaged 2.9 times greater
      than that of cecropin B. Analysis of the peptides produced by endopeptidase
      activity in potato iF indicated that the 5.7-fold lower degradation rate of MB39
      was associated with the substitution of valine for methionine at residue 11 of
      cecropin B. These findings point to the possibility of tailoring antimicrobial
      protein genes to reduce the rate of protein degradation in a particular target
      crop.

PMID- 9150600
TI  - VR-ACS6 is an auxin-inducible 1-aminocyclopropane-1-carboxylate synthase gene in
      mungbean (Vigna radiata).
AB  - We have isolated four cDNA clones of ACC synthase from etiolated mungbean
      seedlings treated with auxin. pVR-ACS2, pVR-ACS3 and pVR-ACS6 contained the same
      sequences as the previously reported DNA fragments, pMAC2, pMAC3 (Botella et al.
      1992b) and pMBA1 (Kim et al. 1992), respectively. pVR-ACS1 was identical with
      pAIM-1 (Botella et al. 1992a). VR-ACS6 was specifically induced in response to
      the auxin signal. The IAA-induction of VR-ACS6 was very rapid (within 30 min) and
      insensitive to cycloheximide treatment at concentrations up to 100 microM.
      Significant accumulation of VR-ACS6 mRNA was detected at 1 microM IAA. The IAA
      induced expression of VR-ACS6 was suppressed by ABA and ethylene, but enhanced by
      BA. These characteristics of VR-ACS6 expression were well correlated with the
      physiological data of auxin-induced ethylene production in mungbean hypocotyls.
      VR-ACS1 was strongly induced by cycloheximide, but was found to be not auxin
      specific. Inhibitors of either ethylene biosynthesis (AOA) or action (NBD)
      increased the basal level of VR-ACS1 mRNA.

PMID- 9150601
TI  - A serine/threonine protein kinase gene isolated by an in vivo binding procedure
      using the Arabidopsis floral homeotic gene product, AGAMOUS.
AB  - During the course of characterizing fragments bound to an Arabidopsis floral
      protein AGAMOUS in vivo, a gene encoding a putative serine/threonine protein
      kinase was found on one of the fragments. The deduced 426 amino acid residues of
      the gene, named APK2a, are 65% identical to a previously reported Arabidopsis
      serine/threonine protein kinase, APK1a. The gene is composed of 6 exons and maps
      at 10 cM from the upper end of chromosome 1. Northern hybridization experiments
      indicated that the gene is strongly expressed in leaves, moderately in roots, and
      very weakly in flowers. Further in situ analysis of the expression in floral buds
      showed that the APK2a gene is expressed at pedicels, is not expressed at the
      floral organ primordia of wild type floral buds, but is moderately expressed in
      the floral organ primordia of the agamous mutant. In vitro binding assay suggest
      that the AGAMOUS protein binds to a sequence similar to, but different from, the
      known MADS-binding consensus sequences, the CArG box, located 3' downstream of
      the APK2a gene. These results suggest that APK2a expression is negatively
      regulated by the AG protein. A close homologue of the APK2a gene, named APK2b,
      was also isolated from the Arabidopsis cDNA library. The expression pattern of
      the APK2b gene differs from that of APK2a. It is strongly expressed in leaves,
      moderately in flowers, and weakly in roots.

PMID- 9150602
TI  - Accumulation of a glycoprotein that is homologous to a seed storage protein in
      mung bean hypocotyls at the late stage of tissue elongation.
AB  - Physiological changes were examined in the amount of a 50-kDa glycoprotein (gp50)
      that was recovered in a nuclear fraction from hypocotyls of mung bean (Vigna
      radiata) seedlings. Immunoblot analysis indicated that the glycoprotein was
      present in hypocotyls and epicotyls from 4- and 5-day-old seedlings but not in
      hypocotyls from 2-day-old seedlings. The glycoprotein was not detected in leaves
      or roots. When we divided hypocotyls of 3-day-old seedlings into elongating
      region (0 to 1.5 cm below the cotyledon) and the mature region, we found gp50 in
      the mature region only. The results suggest that the 50-kDa glycoprotein is
      synthesized de novo and accumulates at the late stage during elongation of cells
      in the hypocotyl. Furthermore, an antibody specific to gp50 reacted with a major
      50-kDa protein in cotyledons, which is known as a storage protein in mung bean
      cotyledon. Eighteen amino acid residues among 22 amino-terminal residues of gp50
      were identical to those of the storage protein from cotyledon. A peptide map of
      the glycoprotein after digestion with V8 protease was similar to that of the
      storage protein. Overall, our findings suggest that the glycoprotein recovered in
      the nuclear fraction is an isoform of the seed storage protein that is expressed
      only in the mature cells of hypocotyls and epicotyls.

PMID- 9150603
TI  - Identification of stylar RNases associated with gametophytic self-incompatibility
      in almond (Prunus dulcis).
AB  - Stylar proteins of 13 almond (Prunus dulcis) cultivars with known S-genotypes
      were surveyed by IEF and 2D-PAGE combined with immunoblot and N-terminal amino
      acid sequence analyses to identify S-RNases associated with gametophytic self
      incompatibility (SI) in this plant species. RNase activities corresponding to Sa
      and Sb, two of the four S-alleles tested, were identified by IEF and RNase
      activity staining. The Sa-RNase band reacted with the anti-S4-serum prepared from
      Japanese pear (Pyrus serotina); no reaction with the antiserum was observed with
      the Sb-RNase band. When the Sa-RNase band was excised from an IEF gel stained for
      RNase activity, subjected to SDS-PAGE, and detected by immunoblotting, it
      appeared that this band consisted of a single protein that reacted with the anti
      S4-serum with M(r) of about 28 kDa. With 2D-PAGE and silver staining of the
      stylar extracts, all four S-proteins could be successfully distinguished from
      each other in the highly basic zone of the gel. Although Sb-, Sc-, and Sd
      proteins had roughly the same M(r) of about 30 kDa, the Sc-protein seemed to be
      slightly smaller than the Sb-protein and slightly larger than the Sd-protein. In
      2D-PAGE profiles as well, the Sa-protein had M(r) of about 28 kDa, apparently
      smaller than the other three proteins. A bud sport, in which one of the two S
      alleles of the original cultivar is impaired, was visualized as a loss of Sc
      protein, which is consistent with the previous pollination study. All four S
      proteins reacted with the anti-S4-serum, probably because of the differing
      conformations of these S-proteins in the IEF and 2D-PAGE gels. The Sa-protein in
      2D-PAGE appeared to be identical to Sa-RNase in IEF; both had the same M(r) and
      were reactive with the anti-S4-serum. N-terminal amino acid sequence analysis of
      the four S-proteins revealed that they were highly homologous to each other and
      similar to the S-RNases of Malus, Pyrus, Scrophulariaceae, and Solanaceae. Taken
      together, RNases in the style are strongly suggested to be associated with the
      gametophytic SI of almond. This is the first report identifying and
      characterizing S-RNase in almond.

PMID- 9150604
TI  - Inhibition by 1-aminocyclobutane-1-carboxylate of the activity of 1
      aminocyclopropane-1-carboxylate oxidase obtained from senescing petals of
      carnation (Dianthus caryophyllus L.) flowers.
AB  - We partially purified 1-aminocyclopropane-1-carboxylate (ACC) oxidase from
      senescing petals of carnation (Dianthus caryophyllus L. cv. Nora) flowers and
      investigated its general characteristics, and, in particular, the inhibition of
      its activity by ACC analogs. The enzyme had an optimum pH at 7-7.5 and required
      Fe2+, ascorbate and NaHCO3 for its maximal activity. The Km for ACC was
      calculated as 111-125 microM in the presence of NaHCO3. Its M(r) was estimated to
      be 35 and 36 kDa by gel-filtration chromatography on HPLC and SDS-PAGE,
      respectively, indicating that the enzyme exists in a monomeric form. These
      properties were in agreement with those reported previously with ACC oxidases
      from different plant tissues including senescing carnation petals. Among six ACC
      analogs tested, 1-aminocyclobutane-1-carboxylate (ACBC) inhibited most severely
      the activity of ACC oxidase from carnation petals. ACBC acted as a competitive
      inhibitor with the Ki of 20-30 microM. The comparison between the Km for ACC and
      the Ki for ACBC indicated that ACBC had an affinity which was ca. 5-fold higher
      than that of ACC. Whereas ACC inactivated carnation ACC oxidase in a time
      dependent manner during incubation, ACBC did not cause the inactivation of the
      enzyme. Preliminary experiments showed that ACBC and its N-substituted
      derivatives delayed the onset of senescence in cut carnation flowers.

PMID- 9150605
TI  - Somatic excision of the Ac transposable element in transgenic Arabidopsis
      thaliana after 5-azacytidine treatment.
AB  - We have introduced the maize Ac transposable element in Arabidopsis thaliana and
      found that after three selfing generations, the element is immobile and
      extensively methylated. Moreover, the nopaline synthase (nos) gene present on the
      same transferred T-DNA, was active early after transformation and regeneration,
      but inactive in most of the S1 progeny. We used 5-azacytidine (5AzaC) to
      determine whether a reduction in the methylation would affect both Ac
      transposition and expression of the nos gene. After treatment with 5AzaC doses
      from 0.3 mM to 1.0 mM, approximately 25% of the plants produced detectable
      amounts of nopaline, indicating that the nos gene was reactivated. Using the
      polymerase chain reaction (PCR) to detect the empty donor site left by Ac
      transposition, we demonstrated that 5AzaC also activates Ac excision in the
      transgenic plants. Approximately 13% of the 5AzaC treated plants (doses from 0.1
      mM to 1.0 mM) were shown to have empty donor sites due to Ac excision. None of
      the plants cultivated in the absence of 5AzaC showed evidence for Ac
      transposition or reactivation of the nos gene. Further analysis using Southern
      blot indicate that some demethylation occurred in the genome of individual
      plants. These results may represent demethylation in few cells during development
      which may be sufficient to reactivate in these cells the expression of the nos
      and Ac transposase transgenes, the latter promoting Ac transposition in somatic
      cells.

PMID- 9150606
TI  - A rapid increase in the level of binding protein (BiP) is accompanied by
      synthesis and degradation of storage proteins in pumpkin cotyledons.
AB  - The binding protein (BiP) has been implicated in cotranslational folding of
      nascent polypeptides, and in the recognition and disposal of aberrant
      polypeptides. To elucidate the involvement of BiP in the biosynthesis of vacuolar
      proteins, we have characterized the protein in pumpkin cotyledons during seed
      maturation and seedling growth. Isolated microsomes from maturing pumpkin
      cotyledons contained a significant amount of BiP, protein-disulfide isomerase and
      calreticulin. We have purified a 70-kDa protein; sequences of the N-terminus and
      internal fragments of this protein exhibited a high identity to the sequence of
      soybean. Immunoblot analysis with specific antibodies raised against the purified
      BiP showed that the amount of BiP in a cotyledon increased markedly at the middle
      stages and then decreased. The increase was accompanied by the synthesis of
      storage proteins and the development of the endoplasmic reticulum in the
      cotyledons at the middle stage of seed maturation. Most of these storage proteins
      degraded dramatically between 2 and 5 days after seed germination, and the
      degradation was also accompanied by a rapid increase in the level of BiP.
      Subcellular fractionation of the 4-day-old cotyledons showed a high accumulation
      of BiP in the endoplasmic reticulum. It is possible that BiP might be involved in
      the synthesis of seed storage proteins during maturation and in the synthesis of
      hydrolytic enzymes responsible for the degradation of the storage proteins during
      seed germination.

PMID- 9150607
TI  - Cloning and functional expression of a novel geranylgeranyl pyrophosphate
      synthase gene from Arabidopsis thaliana in Escherichia coli.
AB  - A gene encoding a novel geranylgeranyl pyrophosphate (GGPP) synthase from
      Arabidopsis thaliana has been identified and termed GGPS5. The gene has been
      sequenced and expressed in Escherichia coli. The deduced amino acid sequence
      showed 64.5% and 57.5% identify with a putative GGPP synthase from Arabidopsis
      and Capsicum annuum, respectively. GGPP enzymatic activity was detected in E.
      coli cells expressing the GGPS5 gene in two different ways. One was the direct
      measurement of GGPP synthase activity in cell extracts and the other was the
      yellow color production of cells when the GGPS5 gene was co-expressed with crtB,
      crtI, crtY and crtZ genes derived from Erwinia uredovora.

PMID- 9150608
TI  - Cloning of a rice cDNA encoding a transcription factor homologous to barley
      GAMyb.
AB  - A cDNA clone, OsGAmyb, which encodes a homologue to the barley Myb-like
      transcription factor, HvGAMyb, was isolated from a rice endosperm cDNA library.
      The clone was used to show that expression of the OsGAmyb gene in aleurone cells
      was stimulated by gibberellic acid and the gene product was shown to
      transactivate an alpha-amylase gene promoter in transient expression analyses.

PMID- 9150609
TI  - Heterologous expression and subcellular localization of pumpkin seed tonoplast
      intrinsic proteins (TIP) in yeast cells.
AB  - Two tonoplast intrinsic proteins (TIP) of pumpkin seeds, pMP23 and MP28, were
      expressed in yeast cells under control of the GAL1 promoter, and the subcellular
      localization of the proteins was analyzed. The pMP23 and MP28 stably accumulated
      in the yeast vacuolar membrane when the proteins were expressed in the proteinase
      A-deficient strain (pep4), which lacks the activities of vacuolar proteases.
      However, pMP23 and MP28 did not accumulate in the wild-type strain; the expressed
      pMP23 and MP28 were degraded in a proteinase A-dependent manner. These results
      indicate that pMP23 and MP28 are transported to the vacuolar membrane when
      expressed in yeast.

PMID- 9150610
TI  - Rapid reconstitution of tonoplast H(+)-translocating pyrophosphatase from
      cultured rice cells into liposomes.
AB  - We report the rapid and functional reconstitution of H(+)-pyrophosphatase (H(+)
      PPase) from the tonoplast of cultured rice (Oryza sativa L.) cells to
      proteoliposomes. The CHAPS-solubilized H(+)-PPase was incorporated into liposomes
      by gel-filtration. Both the activities of PPi-hydrolysis and H(+)-pumping were
      influenced by the lipid-protein ratio and cholesterol.

PMID- 9150611
TI  - Changes in levels of mRNAs for cell wall-related enzymes in growing cotton fiber
      cells.
AB  - mRNAs for cell wall-related enzymes in developing cotton fiber cells were
      measured by reverse transcription-PCR analysis. Both endo-1,4-beta-glucanase and
      expansin mRNA levels were high during cell elongation but decreased when cell
      elongation ceased, and xyloglucan decreased. The endo-1,3-beta-glucanase mRNA
      level was very low in the elongating cells but increased gradually at the onset
      of secondary wall synthesis, accompanying the massive deposition of cellulose.
      Endoxyloglucan transferase and sucrose synthase mRNA levels were constant during
      all stages of growth.

PMID- 9150612
TI  - dad-1, A putative programmed cell death suppressor gene in rice.
AB  - The human dad-1 cDNA homolog was isolated from rice plants. The amino acid
      sequence of the predicted protein product is well conserved in both animals and
      plants. This rice dad-1 homolog can rescue the temperature-sensitive dad-1
      mutants of hamster cells from apoptotic death, suggesting that the rice dad-1
      homolog also functions as a suppressor for programmed cell death.

PMID- 9150613
TI  - SUNCT syndrome. A clinical review.
AB  - The clinical features of SUNCT syndrome have been reviewed in 21 patients. There
      were 17 men and 4 women, rendering a clear male preponderance (ratio of 4.25).
      The mean age at onset was around 51 years. Attacks were experienced mostly in the
      orbital/periorbital area and always recurred on the same side, with an erratic
      temporal pattern and remissions of varying lengths. Most attacks were moderate to
      severe in intensity and burning, electrical, or stabbing in character. The
      attacks were regularly accompanied by prominent, ipsilateral, conjunctival
      injection; tearing; and rhinorrhea or nasal obstruction. There were many
      precipitating mechanisms. Exclusively spontaneous attacks were described in 3
      patients. The usual duration of paroxysms ranged from 10 to 60 seconds, Whereas
      the longest duration varied from 60 to 300 seconds. The frequency of attacks
      during the symptomatic periods varied from less than 1 attack daily to more than
      30 per hour. In the majority of patients, supplementary examinations failed to
      show any notable abnormality. However, 2 patients were documented to have a
      symptomatic form of SUNCT, with a vascular malformation in the ipsilateral
      cerebellopontine angle. A variety of drugs and local anesthetic blockades,
      inclusive of tic douloureux drugs, were tried, but a persistent, convincingly
      beneficial effect was generally lacking. SUNCT syndrome is in the differential
      diagnosis when encountering unilateral, orbital/periorbital headache syndromes.

PMID- 9150614
TI  - Headache during pregnancy and in the postpartum: a prospective study.
AB  - The association between sex hormones and chronic headache has been the subject of
      a good deal of speculation. Headache is predicted to improve during pregnancy,
      when estrogen levels rise steadily until delivery. Retrospective studies have
      suggested that women with a history of migraines do tend to report decreases in
      headache activity with pregnancy. The purpose of this naturalistic study was to
      examine changes in headache that may occur during pregnancy and postpartum in
      women complaining of migraine, tension-type, or combined migraine and tension
      type headaches in a prospective design. Thirty women recorded their headaches
      daily throughout pregnancy and up to 12 weeks postpartum. Results based on these
      ratings demonstrated a nonsignificant trend for headache to decrease throughout
      pregnancy and to increase during the birth week. Headache patterns varied
      slightly depending on headache diagnosis and parity. Contrary to previous
      retrospective study reports, migraine sufferers demonstrated an increase in
      headache in the third trimester. In addition, there was a tendency in multiparous
      women for headaches to increase in the third trimester, whereas primiparous women
      reported less headache activity throughout pregnancy and the postpartum.

PMID- 9150615
TI  - Cerebrospinal fluid neuropeptides and monoaminergic transmitters in patients with
      trigeminal neuralgia.
AB  - The pathogenesis of trigeminal neuralgia remains largely unknown. "Peripheral" as
      well as "central" causes have been suggested. To investigate the role of
      serotonergic, noradrenergic, dopaminergic, and peptidergic systems, we determined
      the concentrations of epinephrine, norepinephrine, and their breakdown product,
      vanillylmandelic acid, in the cerebrospinal fluid of 16 patients (55.3 +/- 8.3
      years) with trigeminal neuralgia. As a marker for the dopaminergic system, we
      determined cerebrospinal fluid concentrations of dopamine and its metabolite,
      homovanillic acid. As a marker for the serotonergic system, we measured
      cerebrospinal fluid levels of the serotonin metabolite, 5-hydroxyindoleacetic
      acid. In addition, levels of the neuropeptides, substance P and somatostatin,
      were determined. The concentration of norepinephrine (P < 0.01) and its
      metabolite, vanillylmandelic acid, (P < 0.05) were significantly decreased in our
      patients. The level of the dopamine metabolite, homovanillic acid, was also
      significantly reduced (P < 0.01). Also significantly decreased was 5
      hydroxyindoleacetic acid (P < 0.01). Substance P was significantly elevated (P <
      0.05). Somatostatin was significantly decreased (P < 0.05). We hypothesize that
      the sum of complex neurochemical changes plays a role in the pathogenesis of
      trigeminal neuralgia. The elevated substance P could support the concept of a
      neurogenic inflammation in the trigeminovascular system, whereas changes in the
      monoaminergic transmitters and their metabolites seem to reflect a more central
      dysfunction possibly due to a longer duration of the disease and an accompanying
      depression.

PMID- 9150616
TI  - Psychophysical precedents of migraine in relation to the time of onset of the
      headache: the migraine time line.
AB  - We conducted a prospective study of 19 female migraine patients who kept a diary
      four times per day at 8 AM, 1 PM, 6 PM, and 11 PM for 10 consecutive weeks. In
      the diary, the patients recorded the occurrence as well as the features and
      associated symptoms of their headaches. They also rated five mood states:
      alertness, tension, irritability, depression, and fatigue, as well as the quality
      of sleep and the incidence and stressfulness of daily hassles as measurements of
      stress. They quantified the variables through the use of 100-mm visual analog
      scales. In the diaries, we identified 68 migraine headaches of which 23 developed
      during the night, 19 during the morning, 16 during the afternoon, and 10 during
      the evening. The headaches which developed during the evening or night were
      preceded by an increased incidence of daily hassles during the afternoon. The
      headaches which developed during the morning or afternoon were preceded by
      increased tension the previous days. The day before the headaches which developed
      during the morning, the incidence of daily hassles was increased during the
      morning, afternoon, and evening. The increased tension at 1 PM was followed by
      increased fatigue at 6 PM, which was still present at 8 AM of the morning during
      which the headaches developed. The day before the headaches which developed
      during the afternoon, the increased tension at 6 PM was followed by increased
      alertness at 11 PM. The next morning, the stressfulness of daily hassles was
      increased at 8 AM, followed by increased tension and irritability at 1 PM. We
      conclude that there are three different sequences of events with regard to the
      psychophysical precedents of migraine, depending on the time of onset of the
      headache: the migraine time line.

PMID- 9150617
TI  - The stress response in headache sufferers: physiological and psychological
      reactivity.
AB  - When examining headache sufferers' reactivity to stress, few studies attend to
      differing characteristics of the environment. In this study, we evaluated the
      influence of the clarity/ambiguity and positive/negative valence of an event on
      subjects' physiological and psychological reactivity. Migraine (n = 30), tension
      (n = 39), and control (n = 35) subjects participated in a laboratory experience
      in which they had to practice and then deliver a news story to a videocamera
      (similar to a newscaster on television). During this experience, they received
      performance feedback and were instructed to try to use the information to improve
      their performance. In reality, this feedback was noncontingent, with subjects
      semirandomly assigned to either a positive, negative, or ambiguous feedback
      condition. Physiological and psychological measures were collected prior to this
      experience, during an anticipation or practice period prior to the newscast, and
      during a recovery period following the delivery of the news story. Results
      suggested that tension subjects might not attend to information from their
      environment when assessing, responding, or reevaluating potentially stressful
      events: relying instead on more global beliefs or attributions. Results also
      indicated that migraine might be associated with a prolonged cardiovascular
      response (i.e., delayed recovery) following a stressful experience.

PMID- 9150618
TI  - Headache in Sweden: the importance of working conditions.
AB  - Headache is a common health problem that causes individual suffering as well as
      public expense. Because epidemiological studies have shown that headache is most
      prevalent among persons younger than 55 years, the influence of working
      conditions is of interest. In this study, we examined the importance of working
      conditions as a risk factor for frequent headache among the general Swedish
      population. Data from the Swedish Survey of Living Conditions for the 2-year
      period, 1988 and 1989, were used. In this survey, a probability sample of the
      Swedish population aged 16 years and older was interviewed. Frequent headache was
      defined as a positive answer to the question, "Have you (during the last 2 weeks)
      had recurrent headache or migraine?" Work stress was studied for two indices:
      physical work stress and mental work stress. The physical work stress index
      contained measurements of seven working conditions, and the mental work stress
      index contained measurements of three working conditions. The proportion of
      persons who reported frequent headache was greater among women than men, and
      frequent headache was most common in the age group 25 to 44 years. The logistic
      regression analyses showed that both physical and mental work stress were
      strongly associated with frequent headache among both men and women even after
      controlling for potential confounders. The associations between work stress and
      frequent headache may be dose-dependent. Heavy mental work stress was most
      strongly associated with frequent headache among men (odds ratio 3.03 [1.92 to
      4.78]) while heavy physical work stress was most strongly associated with
      frequent headache among women (odds ratio 3.48 [1.13 to 10.65]). Improved working
      conditions could be one way of preventing headache, thereby decreasing individual
      suffering and employer as well as public expense.

PMID- 9150619
TI  - The menstrual cycle and migraine: a time-series analysis of 20 women migraineurs.
AB  - This study examined the prevalence of menstrually related headache and the
      relationship between the menstrual cycle and stress in a group of young women
      migraineurs sampled from a general population. Participants (N = 20) meeting
      International Headache Society criteria for migraine with or migraine without
      sure and not meeting criteria for menstrual migraine, provided daily headache
      activity, perceived stress, cognitive appraisal, and coping strategy data during
      two menstrual cycles. Multiple regression was used to analyze these data
      following a time-series approach in which the phases of the menstrual cycle were
      used as predictors of variation in each participant's headache, stress,
      appraisal, and coping data. Analyses revealed that fewer participants than
      expected showed significant relationships between their menstrual cycle and their
      headache activity (20%). However, for these women the amount of variation
      explained by the menstrual cycle was substantial. We suggest that, though some
      women's migraines vary with their menstrual cycle, the number of women
      substantially affected may be much smaller than has been estimated in the
      literature. Relationships between the menstrual cycle and the stress process were
      also found; however, inconsistencies between this and a previous study in our
      laboratory suggest that the nature of this relationship may vary across women
      migraineurs.

PMID- 9150620
TI  - Headache diary in the diagnosis of childhood migraine.
AB  - The usefulness of a headache diary in the diagnosis of migraine and in the
      clarification of migraine symptoms was studied in 145 children. These children
      belong to a 1-year age cohort of 5356 children that has been followed since
      birth. The children were enrolled in the present study according to their
      headache status in a questionnaire study at the age of 8 to 9 years, at which
      time 50 children had migraine, 43 had nonmigrainous headache, and 52 did not have
      recurrent headache. Information on their present headache status was collected
      with a face-to-face interview at the age of 11 to 13 years and from a headache
      diary after the interview. The children kept the diary for 2 to 7 months.
      Altogether, 72 children had migraine according to the International Headache
      Society criteria for migraine, either in the interview or in the diary. Eight
      children were diagnosed only according to the diary (11.1%). Thirty-three
      children had both migraine attacks and nonmigrainous headache episodes according
      to the diary, even though they were able to report only one type of headache
      episode in the interview. The duration of headache episodes was underestimated in
      the interview, compared to the diary, in the children with migraine. Many
      children recognized new aura symptoms, associated symptoms, and characteristics
      of pain when they started to pay attention to these when filling in the diary
      during the follow-up period. The headache diary is useful in clarifying the
      features of headache attacks and in the diagnosis of headache types in children.

PMID- 9150621
TI  - Twenty-four-hour effectiveness of BMS 180048 in the acute treatment of migraine
      headaches.
AB  - The efficacy of BMS 180048, a 5-HT1 agonist in the acute treatment of a migraine
      headache, was evaluated in 216 patients. Three doses of the study drug were
      compared to placebo. Patients received a single test dose in the physician's
      office while being evaluated with a Holter monitor during a headache-free day.
      They then treated a migraines headache with a single dose of the study drug as an
      outpatient. The 150 mg- and 200-mg doses of BMS were significantly superior to
      placebo on change in pain intensity at 2 hours. Patients treated with BMS 180048
      had a longer duration of response than placebo-treated patients. At the 24-hour
      point, only 24% of the 150-mg group and 25% of the 200-mg group had relapsed,
      compared to placebo which had a 42% relapse rate. It is concluded that BMS 180048
      is an effective compound for the treatment of migraine headaches with a prolonged
      duration of response.

PMID- 9150622
TI  - Idiopathic hypertrophic cranial pachymeningitis: an unusual cause of subacute and
      chronic headache.
AB  - Three cases of idiopathic hypertrophic cranial pachymeningitis are presented. The
      diagnosis was based on the CT scan or MRI findings (or both) of thickened
      enhancing dura. In all cases, meningeal biopsies were performed and microscopic
      findings were compatible with nonspecific inflammation. All cases presented with
      subacute and chronic localized headache. Two cases had associated chronic
      meningitis. One cases presented with a syndrome of multiple cranial nerve
      involvement (polyneuritis cranialis). Corticosteroids, in the form of
      prednisolone 60 mg/day, were effective in all cases. Two cases with less severe
      pachymeningitis received corticosteroids for 2 weeks, then were tapered off in 4
      to 6 weeks. A case with extensive lesions needed a long-term low dosage of
      prednisolone, 5 to 10 mg/day for maintenance therapy. Idiopathic hypertrophic
      cranial pachymeningitis may be related to the Tolosa-Hunt syndrome, the syndrome
      of polyneuritis cranialis, and multifocal fibrosclerosis.

PMID- 9150623
TI  - Botulinum toxin injection for cervicogenic headache.
AB  - We report a 28-year-old woman with a 5-year history of cervicogenic headache
      following a whiplash injury. Her unilateral neck pain, if aggravated by exertion,
      would create a predictable sequence of events leading to a hemicephalgia. She
      proved medically refractory to usual therapies, but had a striking response to a
      single botulinum toxin Injection in her symptomatic trapezius muscle. Repeated
      Injections every 3 months have been required to maintain this benefit. The
      Implications of this observation are discussed.

PMID- 9150624
TI  - Prolotherapy for chronic headache.

PMID- 9150625
TI  - Treatment of headache with bupropion.

PMID- 9150626
TI  - Treatment of acute migraine with intravenous droperidol.

PMID- 9150627
TI  - Impact of two social-cognitive interventions to prevent adolescent substance use:
      test of an amenability to treatment model.
AB  - An amenability to treatment model stipulates that interventions may be
      differentially effective for subgroups of individuals with similar
      characteristics. Using such a model, the present study tests the impact of two
      social-cognitive interventions implemented in the sixth (Intervention I) and
      eighth/ninth (Intervention II) grades on students' skill acquisition and on their
      ninth and tenth grade substance use. A randomized factorial design was used to
      examine main and interaction effects within the context of student family
      household status and gender. Positive program effects were found for Intervention
      II on skill acquisition and overall drug involvement. Interaction effects of
      Intervention II x Family Household Status provided support for the amenability to
      treatment model, but no support for the model was observed based on student
      gender. Possible explanations for the study findings are presented and future
      research directions are proposed to address why differences emerge in amenability
      to intervention and why such differences occur for specific subgroups.

PMID- 9150628
TI  - Enhancing outcomes in an indicated drug prevention program for high-risk youth.
AB  - This study examined the net effects of refining a high school-based indicated
      drug prevention program. The Personal Growth Class (PGC), tailored to meet the
      needs of high-risk youth, was designed to increase control of drug use, school
      performance, and emotional well-being. The program integrates social support and
      life-skills training. Process evaluation revealed the need for program
      enhancements to address underestimated levels of depression, anger, and suicidal
      behaviors prevalent among high-risk youth and to ensure that core content was
      being emphasized consistently. Youth participating in Late cohorts received the
      refined PGC with enhanced skills training. Study participants (N = 280) were
      youth, primarily ages fifteen to-seventeen, at high-risk for school failure or
      dropout. Indicators of emotional well-being (e.g., depression, stress, anger,
      self-esteem, personal control), drug involvement, and school performance were
      compared for Late versus Early cohorts. Regression analyses revealed the Late
      versus Early cohorts showed significantly greater decreases in hard drug use,
      depression, perceived stress, and anger, and greater increases in self-esteem.
      The results support arguments that effective indicated prevention programs should
      target specific high-risk youth employing strategies to counteract the
      multifaceted risk factors they experience and enhance needed protective factors.

PMID- 9150629
TI  - Salience of alcohol expectancies and drinking outcomes.
AB  - There is a body of research which indicates that endorsement of positive alcohol
      expectancies predicts alcohol drinking patterns; however, there is inconsistency
      in the literature regarding which particular alcohol expectancies predict
      drinking. Although an individual may endorse a variety of alcohol expectancy
      beliefs, these beliefs may not be of equal importance to drinking decisions. This
      study investigated whether the prediction of drinking might be enhanced by
      considering salience of alcohol expectancies rather than mere endorsement.
      Hierarchical regression analyses demonstrated that expectancy salience
      significantly improved the prediction of total alcohol consumption above and
      beyond the effects of expectancy endorsement. Expectancy salience was less
      effective as a predictor of heavy drinking.

PMID- 9150630
TI  - Experimental evaluation of "The Images Within": an alcohol education and
      prevention program.
AB  - A program titled "The Images Within" was implemented and evaluated in three sites
      on the east coast of the United States. This school curriculum uses art work
      developed by children of alcoholics to stimulate classroom discussions of the
      problems of parental alcohol abuse. The evaluation with 278 experimental and 310
      control students indicated increased knowledge about the effects of alcohol and
      improved skills in coping with alcohol problems and help seeking behavior.
      Process data indicated that related programs were initiated, students were
      stimulated by the program and teachers were positive in their perceptions of the
      program. Schools implementing this program need to have developed referral
      networks to handle the individual concerns that are expressed as a result of
      participation in "The Images Within."

PMID- 9150631
TI  - Environmental predictors of drinking and drinking-related problems in young
      adults.
AB  - We examined relationships among drinking norms, peer alcohol use, alcohol
      availability, drinking location, alcohol consumption, and drinking-related
      problems among young adult drinkers. The specific objectives of our study were to
      assess the relative contribution of normative and physical environmental factors
      to drinking and drinking consequences. Subjects were 3,095 young adults, aged
      eighteen to twenty years old who participated in the Communities Mobilizing for
      Change on Alcohol Project baseline survey. Alcohol consumption (i.e., number of
      drinks on the last occasion) and drinking consequences served as dependent
      variables. Multiple linear regression was used to identify predictors of alcohol
      consumption, and logistic regression was employed to identify predictors of
      drinking consequences. Drinking norms and peer alcohol use were positively
      related to alcohol consumption and to drinking consequences. Drinking in a public
      setting was positively related to alcohol consumption, but not to drinking
      related problems. Findings suggest that policies and programs that alter the
      normative and physical environment surrounding drinking may reduce alcohol
      consumption and subsequent problems in young adults.

PMID- 9150632
TI  - A test of magnitude: does the strength of predictors explain differences in drug
      use among adolescents?
AB  - Prior research has provided much needed information on the association between
      gender, race, predictive factors, and drug use. However, none have provided
      conclusive evidence regarding the extent to which gender and race differences, or
      their interaction, in adolescent drug use is accounted for by predictors. Using
      data on adolescents in four public schools, this study examined variations in the
      comparative strength of predictors of self-reported drug use. Data were collected
      as part of an ongoing longitudinal study of a federally funded multi-model
      program intervention for the prevention of alcohol and drug abuse among high risk
      youth. Analysis of variance was used to examine gender by race differences in
      predictors and drug use and logistic regression was used to assess the
      comparative strength of predictors of adolescent drug use and to explore the
      effect of gender by race on the decision to use drugs. Findings indicated, in
      general, whites, both male and female, had a significantly stronger positive
      association between predictors and drug use relative to blacks. Regarding the
      effect of gender by race on the decision to use drugs, these data indicate, with
      or without adjustments, white females were most likely to use gateway substances,
      followed by white males.

PMID- 9150633
TI  - Putting choice back into the health care equation.

PMID- 9150634
TI  - Assessing risk.

PMID- 9150635
TI  - G.P. vs. specialist.

PMID- 9150636
TI  - Impressions.

PMID- 9150638
TI  - Gum disease may increase risk of heart disease.

PMID- 9150637
TI  - Casting alloys.

PMID- 9150639
TI  - Steroid inhalers and glaucoma.

PMID- 9150640
TI  - New developments in resin restorative systems.
AB  - Efforts have been made during the last several years to develop polymer
      formulations that could replace ceramic materials for the restoration of occlusal
      surfaces. In most cases, resins have exhibited insufficient wear resistance,
      whereas the ceramic materials have had a history of excessively abrading whatever
      opposes them occlusally. Based on recent clinical information, it appears that
      major successes have been achieved in reaching the goal. The author discusses
      these advances and proposes a possible replacement for amalgam, based on new
      technology.

PMID- 9150641
TI  - Investigating the range of surgical effects on soft tissue produced by a carbon
      dioxide laser.
AB  - The authors investigated the surgical and collateral effects on soft tissue of a
      carbon dioxide laser emitting at 9.3 micrometers. Specifically, incision widths
      and depths as well as effectiveness were studied. Three different laser modes
      were investigated: gated continuous wave, or Cw, Superpulse and OptiPulse
      (Medical Optics). Incision depths correlated positively with average power;
      higher powers produced deeper incisions. The gated Cw mode quickly produced wide,
      deep incisions; Superpulse achieved narrower, deep incisions; OptiPulse caused
      very narrow, shallow incisions. Collateral damage to adjacent tissues was reduced
      by a factor of about 2 using Superpulse, and by a factor of 10 using OptiPulse. A
      wide range of effects is achieved in soft tissue, depending on the laser
      parameter combination used.

PMID- 9150642
TI  - Assessing dental anxiety, dental care use and oral status in older adults.
AB  - This study examined associations between dental anxiety and dental care use and
      oral health status in dentate older adults. Analysis of data from the Piedmont
      65+ Dental Study revealed that aspects of dental care use and oral health status
      were independently associated with high dental anxiety. These results suggest
      that measures to control dental anxiety may help to improve dental care use and
      oral health status in older adults.

PMID- 9150643
TI  - Effects of smoking and smoking cessation on healing after mechanical periodontal
      therapy.
AB  - This study investigated the effect of cigarette smoking on 143 patients' clinical
      and microbiological responses to mechanical therapy. Treatment included four to
      six sessions of subgingival scaling and root planing and instruction in oral
      hygiene. Results indicate that current smokers have less healing and reduction in
      subgingival Bacteroides forsythus and Porphyromonas gingivalis after treatment
      compared to former and nonsmokers, suggesting that smoking impairs periodontal
      healing. As the healing and microbial response of former smokers is comparable to
      that of nonsmokers, smoking cessation may restore the normal periodontal healing
      response.

PMID- 9150644
TI  - Patterns of TMJ surgery: evidence of sex differences.
AB  - This study investigated the records from one insurance company's reimbursed
      claims for any TMD-related treatment. Females were disproportionately represented
      among those treated by surgical means.

PMID- 9150645
TI  - A chemical treatment regimen to reduce bacterial contamination in dental
      waterlines.
AB  - This article describes a pilot study in which the authors used aerobic bacterial
      cultures to compare the effects of 1:10 mouthwash, 1:20 mouthwash and 2 percent
      ethanol in reservoir systems with seven conventional water systems. The long
      term, low-concentration antiseptic reduced bacteria to within acceptable limits.

PMID- 9150646
TI  - Combining reconstructive and regenerative therapies.
AB  - The authors used combined reconstructive and regenerative therapy to treat a
      patient who had a surgically created osseous defect that also was associated with
      a perforated root canal. The defect involved a maxillary canine that exhibited 10
      millimeters of attachment loss on its mesial surface. Tetracycline root surface
      conditioning, glass ionomer cement, a decalcified freeze-dried bone allograft and
      an expanded-polytetrafluorethylene membrane were used to achieve a 7- to 8-mm
      gain in clinical attachment level two years after the initial surgery. This case
      illustrates the use of glass ionomer cement, in conjunction with regenerative
      therapy, to effectively treat a root perforation adjacent to a periodontal
      osseous defect.

PMID- 9150647
TI  - When it is best to remove a tooth.

PMID- 9150649
TI  - Painless palatal anesthesia.

PMID- 9150648
TI  - Diabetes, clinical dentistry and changing paradigms.

PMID- 9150650
TI  - Antibiotic use in dentistry. ADA Council on Scientific Affairs.
AB  - Although microbial resistance to antibiotics is increasing rapidly and alarmingly
      throughout the world, dentistry has been relatively conservative with antibiotic
      use and probably has not contributed greatly to the problem. The ADA Council on
      Scientific Affairs has prepared this statement on the use of antibiotics in
      dentistry to clarify the profession's role in combating the growing microbial
      resistance to this popular class of drugs.

PMID- 9150651
TI  - Dental hygienists in the United States: results of an ADA survey.
AB  - The Survey Center of the American Dental Association conducts an annual survey of
      approximately 5 percent of all private practitioners in the United States. This
      survey is sent to a randomly selected group of dentists in private practice,
      including general practitioners and specialists and ADA members and nonmembers.
      It attempts to collect information on various practice characteristics such as
      work schedules, patient visits, non-dentist staff employment, expenses and wages.
      Using information from the 1991 to 1995 Survey of Dental Practice reports, this
      article examines the employment of dental hygienists.

PMID- 9150652
TI  - Who's to blame?

PMID- 9150653
TI  - Public health and optometry--an eye on prevention.

PMID- 9150654
TI  - Optometrists in the media.

PMID- 9150655
TI  - Xalatan difficulties.

PMID- 9150656
TI  - No calculations required.

PMID- 9150657
TI  - Contact lens use after corneal trauma.
AB  - BACKGROUND: This study was performed to explore the epidemiology and visual
      outcomes of major anterior segment trauma cases referred to the Contact Lens
      Service (CLS) in a large, urban, eye trauma center at a university hospital.
      METHODS: All eye trauma patients seen on the CLS at The University of Illinois in
      Chicago for a 2-year period were identified (n = 122). A search of all eye trauma
      cases seen at UIC (n = 2279) during the same period yielded 757 cases with the
      same diagnostic codes. RESULTS: CLS cases represent 16.1% of cases with similar
      diagnoses and 5.35% of all cases seen during the period of study. Cases were
      predominantly young men (mean age, 28 years). The mean age for CLS cases (mean
      age, 17 years) was significantly younger. Best-corrected visual acuity was 20/100
      or better in 75% of cases with a contact lens and in 68% of cases with a
      spectacle lens; 82% of CLS cases had iris damage versus 14.5% of non-CLS cases;
      73% of CLS cases were aphakic; 105 CLS cases were given contact lenses. Mean
      follow-up time was 24 months. Mean wearing time was 11 hours/day. On interview,
      35 of 79 cases (44%) continued to wear lenses. CONCLUSIONS: Cases referred to the
      CLS tended to be young men with unilateral injuries-predominantly open globes
      with resultant aphakia and iris damage. Good visual acuity was achieved in most
      cases. Long-term success wearing contact lenses for this population was poor,
      suggesting that alternatives to contact lens wear should be more actively
      considered.

PMID- 9150658
TI  - Hazardous chemical exposure: guidelines for the optometric office.
AB  - BACKGROUND: The Occupational Safety and Health Administration (OSHA) Hazard
      Communication Standard (HCS) applies to all types of employers, including
      optometrists. The purpose of the standard is to ensure that employees are aware
      of chemical hazards in the workplace and know how to protect themselves. Any
      optometric office that uses chemicals such as acetone, alcohol, lens-tinting
      dyes, or disinfection chemicals must comply with HCS. METHODS: Optometrists must
      develop, implement, and maintain a written Hazard Communication Program for their
      practices. The program must describe how they plan to meet the requirements of
      HCS. It should include the development of a listing of all hazardous chemicals
      used in the office, the collection of appropriate Material Safety Data Sheets
      (MSDS) for each chemical, the labeling of hazardous chemical containers, and the
      provision of an effective employee-training program. RESULTS: The implementation
      of an effective Hazard Communication Program will help ensure employee safety. A
      sample outline for a Hazard Communication Program for an optometric office is
      provided. CONCLUSIONS: Optometrists with one or more employees have an obligation
      to ensure these employees are provided with a healthy and safe workplace. OSHA
      has established specific requirements relating to employees' potential exposure
      to chemicals. Failure to comply with OSHA regulations may result in significant
      fines.

PMID- 9150659
TI  - A primary care team approach to the prevention of ocular complications of
      diabetes: a program review.
AB  - BACKGROUND: Diabetes mellitus is a serious public health concern. Approximately
      7.8 million Americans have been diagnosed with the disease. Researchers estimate
      an additional 6 to 7 million individuals currently have the disease, but remain
      undiagnosed. Diabetes is the leading cause of new blindness in Americans 20 to 74
      years of age. Disproportionately high rates of diabetes exist within Native
      American, Hispanic, and black populations. METHODS: This process review documents
      the experiences of a collaborative primary care team approach to the prevention
      and treatment of ocular complications of diabetes in patients receiving care at
      the White Earth Indian Health Center, Bemidji Area Indian Health Service. The
      White Earth Indian Health Center was one of four primary care clinics that pilot
      tested the Minnesota Department of Health Diabetes Control Program. RESULTS: The
      rate of diabetic eye examination increased to 86% of all individuals diagnosed
      with diabetes. CONCLUSIONS: This article describes the experiences of the White
      Earth Indian Health Center in establishing priorities, selecting guidelines, and
      implementing and monitoring a pilot-project for the prevention of ocular
      complications of diabetes. Application or modifications of this model may be of
      benefit to other programs that use the primary care team approach in the care and
      management of diabetes and other chronic disease entities.

PMID- 9150660
TI  - Effects of changes in lighting level on performance with the AcuVision 1000.
AB  - BACKGROUND: The AcuVision 1000 Trainer is an instrument designed to assess and
      train eye-hand coordination in athletes. Variable environmental conditions are
      encountered when sports-vision screenings are performed. The effect of these
      factors on scores attained on sports-vision testing equipment is an important
      consideration when results for different populations are compared. METHODS: This
      study investigated the effect of different lighting levels on subject
      performance. Twenty-five subjects performed three trials at each of three
      lighting levels (day-light, dim room, and dark. The presentation order of
      lighting level was counterbalanced and subjects were randomly assigned to the
      various presentation orders. RESULTS: The results indicate a statistically
      significant difference in performance at the various levels. High lighting levels
      decreased scores significantly, whereas there was no significant difference
      between the two lower levels. CONCLUSIONS: This study emphasizes the effect
      lighting can have on performance, and illustrates the need to properly control
      environmental factors through well-defined testing protocols for the use of the
      AcuVision 1000.

PMID- 9150661
TI  - Ocular ischemic syndrome as initial manifestation of bilateral carotid occlusive
      disease.
AB  - BACKGROUND: The ocular ischemic syndrome is a rare constellation of ocular signs
      and symptoms that are secondary to severe carotid artery stenosis. The patient
      may report decreased vision and ocular pain, while objective findings are
      variable and include midperipheral dot and blot hemorrhages, rubeosis (with or
      without neovascular glaucoma), a mid-dilated and poorly reactive pupil, and
      uveitis. The visual prognosis is generally poor, and treatment is primarily aimed
      at management of the underlying carotid occlusive disease. METHODS: Two cases are
      presented in which the ocular ischemic syndrome was the initial manifestation of
      complete bilateral internal carotid artery occlusion. Both patients experienced
      severe unilateral loss of vision. Internal carotid endarterectomies could not be
      performed, so medical and surgical management concentrated on maintenance of
      vascular collateral pathways. CONCLUSIONS: The ophthalmic complications of the
      ocular ischemic syndrome can be devastating--the underlying systemic conditions
      are life-threatening. It is imperative the clinician be aware of the signs and
      symptoms of carotid artery disease in order to facilitate prompt diagnosis and
      appropriate referral.

PMID- 9150663
TI  - ECG of the month. Alien intruders. Ventricular parasystole.

PMID- 9150662
TI  - The artist and defective sight (a book review and commentary).
AB  - BACKGROUND: Many authors have wondered if an artist "sees" things differently
      because of a vision disorder. For example, if a famous artist has a color
      deficiency, what would the effect be on his paintings? Would a painting be
      affected by a cataractous eye--or by presbyopia--or by diabetic retinopathy? Such
      questions have always interested the eye and vision specialist. METHODS/RESULTS:
      A 1970 book entitled The World Through Blunted Sight, written by British
      ophthalmologist Patrick Trevor-Roper, attempts to answer those questions.
      CONCLUSIONS: Interesting speculations are offered about the effects of myopia,
      astigmatism, presbyopia, and altered color vision on the works of such well-known
      artists as Monet, Holbein, Whistler, Gainsborough, and many others.

PMID- 9150664
TI  - Stridor in the neonate: laryngomalacia.
AB  - Stridor in the neonate is usually congenital in etiology, the most common cause
      being laryngomalacia. Emergency airway management is always the first priority.
      The history is highly suggestive of the diagnosis in the majority of cases, but
      endoscopy is required for confirmation. The possibility of synchronous lesions
      must not be overlooked. Laryngomalacia presents with stridor usually within the
      first few weeks of life. The stridor is inspiratory in nature and varies with
      position and activity level. Anatomic, histologic, and neurologic factors have
      been proposed as the cause of laryngomalacia. Patients typically have a benign
      form of the disease, which they outgrow by age two. A small percentage of
      patients will have a severe form of the disease requiring surgical intervention.

PMID- 9150665
TI  - A 31-year-old woman with lupus erythematosus and fatal multisystem complications.
AB  - A 31-year-old woman with systemic lupus erythematosus presented with respiratory
      and renal symptoms followed by abdominal pain and seizure. Clinical diagnoses of
      lupus pneumonitis, nephritis, vasculitis, and cerebritis were made. The patient
      had a progressively downhill course with pancytopenia and hemolysis treated with
      aggressive immunosuppressive therapy and extended plasmapheresis. Lupus
      pneumonitis leading to diffuse alveolar damage was the immediate cause of death.
      Diffuse proliferative lupus nephritis was seen in the biopsy, and the autopsy
      demonstrated thrombotic microangiopathy. Extra-renal complications of lupus and
      response to therapy are discussed in the format of a Tulane Clinicopathologic
      Conference.

PMID- 9150666
TI  - Radiology case of the month. Chronic seizure disorder. Arteriovenous
      malformation.

PMID- 9150667
TI  - The Journal 150 & 100 years ago. September 1846 and 1896.

PMID- 9150668
TI  - AIDS orphans in Louisiana in the year 2000: the potential economic impact on the
      foster care system.
AB  - This study estimates the number of AIDS orphans in Louisiana and projects the
      fiscal demand on the state's foster care system in the year 2000. The Michaels
      and Levine model is used to estimate the number of orphans, and state foster care
      data are used to project the placement cost of those AIDS orphans. Between 1992
      and the year 2000, the AIDS orphan count in Louisiana is estimated to range
      between 1,242 and 2,627 infants and children. Black children are estimated to
      comprise the overwhelming majority of this population. If only 50% of the AIDS
      orphans this study projects for the year 2000 require foster care services, the
      state of Louisiana would need additional revenues for that year alone, ranging
      from $308,112 to $624,546, to serve those new entrants. This study provides a
      critical starting point for state policy planning. The AIDS orphan population in
      Louisiana is growing each year and the needs of these infants and children must
      be anticipated and accommodated.

PMID- 9150669
TI  - Nosocomial central venous catheter-related infections in intensive care units.
AB  - To examine the recent microbiology of catheter-related infections (CRIs) in the
      intensive care unit (ICU) setting and to determine the association between
      selected factors and mortality among ICU patients diagnosed with a CRI, a
      retrospective review of all ICU patients determined to have a CRI between January
      1992 and December 1994 was undertaken. A total of 108 patients with 111 episodes
      of CRIs were identified. The most common isolate was coagulase negative
      staphylococcus (37.9%), followed by Staphylococcus aureus (20.9%). Methicillin
      resistance was common in both CNS (93%), and S aureus (42%) isolates. Factors
      predictive for death in a multivariate analysis were as follows: male sex
      (relative risk (RR) 2.43, 95% confidence interval (CI) 1.0, 6.07), hypotension
      (RR 6.90, 95% CI 1.56, 12.2), American Society of Anesthesiologist physical
      status score greater than 3 (RR 4.36, 95% CI 1.56, 12.2), and underlying medical
      condition (RR 3.50, 95% CI 1.17, 10.5). This study demonstrated the increasing
      proportion of CRIs due to methicillin-resistant organisms in the ICU. Functional
      status and degree of illness were the strongest predictors for survival in this
      population.

PMID- 9150670
TI  - Neuroretinitis in cat scratch disease associated with macular star.

PMID- 9150671
TI  - Case records of the Department of Medicine University of Mississippi Medical
      Center. Chronic active hepatitis with cirrhosis of liver secondary to alpha-1
      antitrypsin deficiency.

PMID- 9150673
TI  - The Medicare-to-private payment gap: is Medicare the "high" payer? American
      Medical Association Center for Health Policy Research.

PMID- 9150672
TI  - California Proposition 215 and Arizona Health Proposition 200 challenged.

PMID- 9150674
TI  - Blood transfusion quality improvement project findings.

PMID- 9150675
TI  - Saint Gotthard's unwanted burden.

PMID- 9150676
TI  - The fires of Saint Anthony.

PMID- 9150677
TI  - The epidemiology of stroke: a focus on Rhode Island.

PMID- 9150678
TI  - Management of acute strokes.

PMID- 9150679
TI  - Vascular dementia.

PMID- 9150680
TI  - Stroke prevention.

PMID- 9150681
TI  - Stroke research: recent and future.

PMID- 9150682
TI  - First the chicken, then the egg; the heartburn came later.

PMID- 9150683
TI  - Recent cerebrovascular mortality in Rhode Island.

PMID- 9150684
TI  - Hypertension control: progress, but....

PMID- 9150685
TI  - Point of view: for the children of incarcerated addict-mothers, prescription:
      school.

PMID- 9150686
TI  - New HCFA physician incentive plan regulations: a physician's guide.

PMID- 9150687
TI  - Dracunculiasis. Global surveillance summary, 1996.

PMID- 9150688
TI  - Azelastine nasal spray for allergic rhinitis.

PMID- 9150689
TI  - Treatment of Lyme disease.

PMID- 9150690
TI  - The clinical management of hirsutism.

PMID- 9150691
TI  - Extrarenal aspects of angiotensin II function.
AB  - The cloning of angiotensin II (Ang II) receptor genes and the availability of
      specific receptor ligands allows characterization of Ang II receptor-mediated
      actions. Most of the well-known Ang II effects such as vasoconstriction, drinking
      response and cell proliferation are mediated through the AT1 receptor. Little is
      known about the physiological effect of the AT2 receptor, though there are some
      reports describing the involvement of the AT2 receptor in blood pressure
      regulation. Recent data demonstrate that the AT2-mediated actions are inhibitory
      to AT1- and mitogen-induced growth effects, indicating a balancing mechanism for
      Ang II-controlled mechanisms. It has also been demonstrated that AT2 receptor
      inactivation induces endothelial cell proliferation in the presence of Ang II.
      Additionally, AT2 receptor activation enhances nerve growth factor-induced
      differentiation of PCI2W cells and a role in apoptotic changes has also been
      reported. Based on recent findings, this article focuses on the role of Ang II in
      growth and differentiation processes with respect to the AT2 receptor in these
      events.

PMID- 9150692
TI  - Predicting the effects of long-term medical treatment in acromegaly. At what
      cost? For what benefits?

PMID- 9150693
TI  - Obesity and diabetes and the beta-3 adrenergic receptor.

PMID- 9150694
TI  - An important role of IGF-I in intrauterine growth in humans.

PMID- 9150695
TI  - Results of somatostatin receptor scintigraphy do not predict pituitary tumor
      volume- and hormone-response to ocreotide therapy and do not correlate with tumor
      histology.
AB  - The value of somatostatin receptor scintigraphy (SRS) to predict the effect of
      somatostatin analog therapy on pituitary adenomas is not clear, due to the use of
      different radiopharmaceuticals (123I-Tyr3-octreotide and 111In-pentetreotide) and
      the small number of patients in previous studies. We used 111In-pentetreotide
      scintigraphy in 49 patients in order to (i) correlate SRS results with basal
      tumor volume as well as volume- and hormone-response to 3 months of octreotide
      therapy (Oct-Tx). (ii) identify tumor remnants after incomplete surgery and (iii)
      evaluate any correlation with immuno histology. Twenty-five patients had a GH
      secreting adenoma (GH-A, 15 prior to intended surgery, 10 with
      persistent/recurrent disease after previous therapy). Twenty-four patients had a
      clinically non-functioning adenoma (NF-A). For SRS, planar and single photon
      emission computer tomographic images (SPECT) were recorded 4 h and 24 h post
      injection. SRS grading was as follows: GO, no uptake: G1, uptake comparable to
      normal pituitary; G2, increased uptake: G3, very intense uptake. G2/3 was seen in
      8/25 GH-A and in 12/24 NF-A. Pretreatment tumor volume (magnetic resonance
      imaging (MRI) tended to be related to 111In-pentetreotide uptake in GH-A with a
      tumor visible on MRI (G0/1 (n = 10) vs G2/3 (n = 8): 3.6 +/- 1.9 vs 10.5 +/- 6.5
      cm3 (mean +/- S.E.), P = 0.051), but not in NF-A (G0/1 (n = 12) vs G2/3 (n = 12):
      17.0 +/- 10.1 vs 14.3 +/- 3.6 cm3). SRS did not identify a tumor remnant in the 7
      MRI-negative patients with persistent post-operative acromegaly. Basal GH (6-h
      profile) and IGF-1 in GH-A did not correlate with SRS results (G0/1 (n = 17) vs
      G2/3 (n = 8), GH: 32.3 +/- 18.2 vs 29.3 +/- 7.4 micrograms/l IGF-I: 851 +/- 80 vs
      1038 +/- 153 micrograms/l). During Oct-Tx of GH-A neither tumor shrinkage nor GH
      suppression was related to SRS results. In 6 NF-A classified as gonadotropinomas
      (by their plasma glycoprotein hormone or alpha-subunit concentrations, basally
      and/or in response to TRH) 111In-pentetreotide uptake was not different from that
      of the non-gonadotropin/non-secreting adenomas. SRS results were not related to
      the immunohistological subtype in 22 GH-A (monohormonal mixed
      somatotrope/lactotrope, plurihormonal) or in 22 NF-A (null-cell adenomas,
      gonadotropinomas silent hormonal adenomas). We conclude that 111In-pentetreotide
      SRS reflects tumor volume poorly in GH-A and not at all in NF-A. It does not
      predict the effect of Oct-Tx on the volume of both GH-A and NF-A, nor on the GH
      concentration in GH-A. 111In-pentetreotide SRS is unable to identify post
      operative tumor remnants not visible on MRI.

PMID- 9150697
TI  - Apoptosis and p53 suppressor gene protein expression in human anterior pituitary
      adenomas.
AB  - Human anterior pituitary adenomas proliferate and express the p53 tumour
      suppressor gene protein, but it is not known if apoptosis (programmed cell death)
      occurs. Therefore, the detection of apoptosis was undertaken in tumorous human
      anterior pituitary tissue and compared with p53 protein expression, tumour type
      and tumour size. Apoptosis (detected by the in situ end labelling technique) and
      p53 suppressor gene protein (detected by DO.1-antibody immunocytochemistry) were
      determined in formalin-fixed and paraffin-embedded tissue from 37 human pituitary
      adenomas (2 macroprolactinomas, 9 somatotrophinomas and 26 non-functioning
      adenomas). Two normal anterior pituitaries were also included in this study. Pre
      operative tumour size was scored 1 to 4 from magnetic resonance imaging
      radiology. Apoptosis was found in 7 of 29 tumours (24%), 11% of somatotrophinomas
      and 33% of non-functioning adenomas, although this difference was not
      significant. The p53 tumour suppressor protein was found in 7 of 31 tumours
      (23%), 33% of somatotrophinomas and 19% of non-functioning adenomas. Apoptosis
      and p53 protein expression were not found in normal anterior pituitary. In
      conclusion, apoptosis occurs in human anterior pituitary adenomas, but no
      significant association was found between apoptosis and p53 protein expression,
      tumour type or tumour size.

PMID- 9150696
TI  - Growth hormone increases and insulin-like growth factor-I decreases circulating
      lipoprotein(a)
AB  - BACKGROUND: Elevated serum lipoprotein(a) (Lp(a)) is a strong risk factor for
      coronary artery disease (CAD). Genetic factors appear to account for the major
      variance in Lp(a) levels but the contribution hormones make in modulating Lp(a)
      levels is not yet clear. In the present investigation we determined the effects
      of human growth hormone (hGH) and insulin-like growth factor-I (IGF-I) on
      circulating Lp(a). METHODS: Four groups of patients were studied. Group a: adults
      with GH deficiency (n = 7) treated with hGH (0.05 U/kg/day, s.c.); group b: girls
      with Turner syndrome (n = 7) treated with hGH (0.1 U/kg/day, s.c.); group c:
      prepubertal boys with idiopathic short stature (n = 6) treated with the GH
      secretagogue (GHRP) hexarelin (60 micrograms t.i.d. intranasally); group d: Laron
      syndrome patients (n = 10) treated with IGF-I (100-200 micrograms/kg/day, s.c.).
      Following overnight fasting, serum was sampled before the initiation of treatment
      and during 6-9 months treatment. RESULTS: Serum IGF-I rose significantly in all
      the subjects in all four groups. In the first three groups in which IGF-I was
      elevated by exogenous or endogenous GH stimulation, serum Lp(a) increased
      significantly (119 +/- 35%, P < 0.01; 126 +/- 44%, P < 0.05; 102 +/- 29%, P <
      0.01 for groups a, b, and c respectively). By contrast, serum Lp(a) levels
      decreased in group d to whom exogenous IGF-I was administered (-66 +/- 5%, P <
      0.001). The differential effect of endogenous vs exogenous IGF-I on serum Lp(a)
      paralleled the behaviour of serum insulin. Insulin was significantly increased in
      all the subjects receiving hGH or GHRP (65.2 +/- 31%, P = 0.109; 93.7 +/- 53%, P
      = 0.062; 353.8 +/- 52.7%, P < 0.01 for groups a, b, and c respectively) whereas
      insulin levels were reduced following exogenous administration of IGF-I (-34.1 +/
      9.1%, P < 0.01). CONCLUSIONS: We conclude that long-term GH treatment increases
      and IGF-I decreases circulating levels of Lp(a). These findings may have clinical
      relevance in view of the increasing use of hGH in children and adults and the
      role of Lp(a) as a CAD risk factor.

PMID- 9150698
TI  - C-type natriuretic peptide exerts stimulatory effects on the corticotropin
      releasing hormone-induced secretion of hormones in normal man.
AB  - C-type natriuretic peptide and atrial natriuretic peptide have been reported to
      bind to distinct receptors and to exert opposing effects on different systems.
      Although it is known that atrial natriuretic peptide inhibits the corticotropin
      releasing hormone-stimulated hormone release in man, the corresponding action of
      C-type natriuretic peptide has so far not been characterized. We investigated the
      effects of 30-min infusions of 150 and 300 micrograms C-type natriuretic peptide
      on adrenocorticotropin, cortisol, and prolactin release stimulated by 100
      micrograms corticotropin-releasing hormone and on cardiovascular parameters in 8
      healthy male volunteers. Compared with placebo, 300 micrograms C-type natriuretic
      peptide significantly (P < 0.05) enhanced the stimulation of cortisol (area under
      curve (arbitrary units): 520 +/- 35 vs 651 +/- 55) and prolactin (area under
      curve: 29 +/- 3 vs 37 +/- 5). Adrenocorticotropin levels were increased, but the
      differences did not reach statistical significance (maximum increment: 27 +/- 4
      vs 36 +/- 2 pg/ml). C-type natriuretic peptide at a dose of 150 micrograms had no
      clear effect on these hormones and C-type natriuretic peptide also produced no
      cardiovascular or subjective effects. Our data suggest stimulatory effects of C
      type natriuretic peptide on corticotropin-releasing hormone-induced hormone
      release and offer further evidence for a complex role of different natriuretic
      peptides in endocrine regulation.

PMID- 9150699
TI  - Greater disorderliness of ACTH and cortisol release accompanies pituitary
      dependent Cushing's disease.
AB  - We investigated the episodicity of 24-h ACTH and cortisol secretory profiles in
      16 patients with Cushing's disease and 25 healthy matched controls, with a
      recently introduced scale- and model-independent regularity statistic,
      approximate entropy (ApEn). The mean (+/-S.E.M.) ApEn value for plasma ACTH
      concentrations in Cushing's disease was 1.3817 +/- 0.033, and in controls 0.8394
      +/- 0.049 (P < 10(-10)); for plasma cortisol concentrations the values were
      1.4575 +/- 0.052 and 0.8637 +/- 0.020 respectively (P < 10(-10)), implying
      greater irregularity of release for both hormones in Cushing's subjects. The
      calculated sensitivity and specificity of ApEn for ACTH profiles were 94% and
      100% respectively. For cortisol the sensitivity and specificity were both 100%.
      ApEn was not correlated with sex, age, or the total 24-h secretion rate of ACTH
      and cortisol in patients and controls. The increased ApEn in patients with
      Cushing's disease points to an increased disorderliness of ACTH and cortisol
      secretion compared with healthy controls. In conjunction with the available
      literature, we hypothesize more generally that autonomous endocrine tumors may be
      typified by reduced regularity, orderliness, or synchrony of the time structure
      of hormone release.

PMID- 9150700
TI  - Prostate specific antigen in boys with precocious puberty before and during
      gonadal suppression by GnRH agonist treatment.
AB  - In healthy boys, the pituitary-gonadal axis exhibits diurnal variation in early
      puberty. Serum testosterone levels are higher during the night and low or
      immeasurable during the day. These fluctuating levels of circulating androgens in
      early pubertal boys are difficult to monitor. Prostate specific antigen (PSA) is
      a marker of the androgen-dependent prostatic epithelial cell activity and it is
      used in the diagnosis and surveillance of adult patients with prostatic cancer.
      We have measured PSA concentrations in serum from boys with precocious puberty
      before and during gonadal suppression with GnRH agonists to evaluate the effect
      of normal and precocious puberty on PSA levels and to study the correlation
      between testosterone and PSA in boys. METHODS: PSA was measured by an
      ultrasensitive immunofluorometric assay with a detection limit of 0.03
      microgram/l. Testosterone was measured by an RIA with a sensitivity of 0.23
      nmol/l, and sex hormone binding globulin was measured by a time-resolved
      immunofluorescence assay (sensitivity 0.23 nmol/l). Five boys with central
      precocious puberty (CPP) were studied before and after 12 months of GnRH agonist
      treatment. Sixty healthy boys (12 in each Tanner stage of puberty) and 37 healthy
      young males served as controls. RESULTS: PSA levels were immeasurable in all
      prepubertal boys, whereas PSA levels increased with increasing stage of pubertal
      maturation. There was a significant correlation between PSA and testosterone and
      free androgen indices (r = 0.61 and r = 0.65 respectively, both P < 0.001). All 5
      boys with CPP had significantly elevated PSA levels which decreased to very low
      or immeasurable levels after GnRH agonist treatment. CONCLUSION: PSA may be a
      useful marker of testosterone activity in boys with normal or precocious puberty.

PMID- 9150701
TI  - Pulsatile gonadotrophin secretion in hypothyroid women of reproductive age.
AB  - Hypothyroid women may have various disturbances of the reproductive system.
      Although menstrual cycle disturbances and infertility have been reported in
      hypothyroidism, gonadotrophin levels have usually been found in the normal range.
      We have investigated whether female hypothyroid patients of reproductive age have
      any alteration in the pulsatile secretory pattern of gonadotrophin secretion. LH
      and FSH were assayed on days 2-5 of the menstrual cycle in blood samples taken
      every 10 min for 8 h from six hypothyroid women and six age-matched control
      subjects. Pulsatility was analysed using the Cluster and Detect programs. There
      was no significant difference in the number of peaks identified (3.7 +/- 0.8 vs
      3.7 +/- 0.8 for LH, and 3.7 +/- 0.8 vs 4.2 +/- 0.5 for ESH), the mean duration of
      peaks (LH: 68.0 +/- 6.9 vs 72.7 +/- 5.1 min; FSH: 81.9 +/- 8.1 vs 71.2 +/- 10.3
      min), the area under the peaks (LH: 91.5 +/- 20.4 vs 148.2 +/- 55.1 IU/l per min;
      FSH: 71.5 +/- 4.5 vs 62.7 +/- 15.0 IU/l per min), and the incremental amplitude
      from baseline (LH: 2.2 +/- 0.4 vs 3.0 +/- 0.8 IU/l; FSH: 1.4 +/- 0.2 vs 2.1 +/-
      0.5 IU/ l). However, the absolute pulse amplitude was greater in hypothyroid
      patients (LH: 14.5 +/- 1.4 vs 8.3 +/- 1.3 IU/l, P < 0.01; FSH: 9.0 +/- 1.5 vs 5.8
      +/- 1.2 IU/l, P = 0.04), as were the integrated concentrations (LH: 6.6 +/- 0.7
      vs 3.2 +/- 0.4 IU/l per min, P < 0.01; FSH: 4.3 +/- 0.4 vs 2.1 +/- 0.5 IU/l per
      min, P < 0.01). Oestradiol values were comparable in the two groups (42.7 +/- 0.4
      vs 43.5 +/- 9.7 pg/ml). These results indicate that in hypothyroid women there is
      an increased baseline level with a normal pulsatility of the gonadotrophin
      secretion. Similar oestrogen levels in both groups, and normal or near-normal
      cycles in our patients suggest either a decreased biological potency of the
      gonadotrophins or a mild ovarian resistance.

PMID- 9150702
TI  - Lack of relationship between 17-hydroxyprogesterone response to buserelin testing
      and hyperinsulinemia in polycystic ovary syndrome.
AB  - OBJECTIVE: To determine whether hyperinsulinism affects cytochrome P450c17 alpha
      activity by investigating the correlation between 17-hydroxyprogesterone (17-OHP)
      hyper-responsiveness to the gonadotropin-releasing hormone (GnRH) agonist,
      buserelin, and the insulin response to oral glucose in polycystic ovary syndrome
      (PCOS). DESIGN: Ultrasound, clinical and hormonal parameters were used to define
      PCOS in this prospective clinical study. We investigated the correlation between
      the 17-OHP response to buserelin testing and the insulin response to oral glucose
      in PCOS. METHODS: Twenty-eight women with PCOS and eighteen normal women were
      included in the study. 17-OHP response to buserelin, and insulin and C-peptide
      responses to oral glucose were measured. RESULTS: Twenty-five women with PCOS had
      an increased 17-OHP response. The PCOS patients showed significantly higher mean
      post-glucose load insulin and C-peptide levels than controls (P < 0.05). No
      significant correlations were found between basal 17-OHP and fasting insulin or
      fasting C-peptide, between peak 17-OHP and fasting insulin, peak insulin or peak
      C-peptide, between 17-OHP area under the curve (AUC) and insulin AUC or C-peptide
      AUC, and between percent increment in 17-OHP and insulin AUC or C-peptide AUC (P
      > 0.05). CONCLUSIONS: Lack of a relationship between the 17-OHP response to the
      GnRH agonist buserelin and hyperinsulinism suggests that hyperinsulinism may not
      play a role in the dysregulation of the cytochrome P450c17 alpha enzyme seen in
      PCOS.

PMID- 9150703
TI  - Lanreotide in the treatment of patients with thyroid eye disease.
AB  - Octreotide, a potent synthetic somatostatin (SM) analogue, was recently evaluated
      and found to have a beneficial effect in thyroid eye disease (TED), mostly in
      those patients with a positive Octreoscan-111. Lanreotide (LRT; Somatuline
      Ipsen), a new SM long-acting analogue, is more active than natural SM and shows a
      much longer duration of action. The aim of the present preliminary study was to
      evaluate the therapeutic effect of LRT in the treatment of TED. Five patients,
      three males and two females, mean age 50.6 +/- 7.6 S.D. (45-64) years, all with
      severe symptoms of TED were studied. A similar number of patients, matched for
      age, sex and severity of ophthalmopathy served as controls. All the patients and
      controls were investigated with orbital scintigraphy using 111 In DTPA-D-Phe1
      octreotide (Octreoscan-111) and selected on the basis of positive octreoscan. The
      NOSPECS system, as adapted by Donaldson et al. (Journal of Clinical Endocrinology
      and Metabolism 1973 37 276-285) and a disease activity score, as proposed
      recently by an International Workshop, have been followed in this study in order
      to evaluate the response to treatment. The five patients who comprised the
      treatment group received 0.04 g LRT i.m. once every 2 weeks over a period of 3
      months, after which the Octreoscan-111 was repeated. The control patients were
      given an injection of water i.m., also once every 2 weeks for 3 months, after
      which they were evaluated clinically. No Octreoscan-111 was performed in the
      controls. All patients and controls were evaluated by the same physician, who was
      unaware of the type of treatment used. A decrease in the NOSPECS score and the
      clinical activity score was regarded as a positive response, while no change or
      an increase in the NOSPECS score along with no clinical improvement was regarded
      as a negative response. After 3 months of treatment with LRT, four patients
      showed a statistically significant improvement in ophthalmopathy in both eyes and
      one in one eye. Three of the control patients with TED did not show any change,
      one showed a minor improvement in one eye and no change in the other and one
      showed deterioration in both eyes. An interesting finding was that orbital
      Octreoscan-111 activity was absent in all the patients after LRT treatment. In
      conclusion, these preliminary results show that LRT has a beneficial effect on
      patients with TED, and that since it has to be given only once every 2 weeks, it
      is probably superior to any other form of SM treatment. However, as the number of
      patients was small, further studies are needed to confirm our results.

PMID- 9150704
TI  - Molecular analysis of the RET proto-oncogene in patients with sporadic medullary
      thyroid carcinoma: a novel point mutation in the extracellular cysteine-rich
      domain.
AB  - Germline point mutations in the RET proto-oncogene are associated with multiple
      endocrine neoplasia type 2 (2A and 2B) and familial medullary thyroid carcinoma.
      On the other hand, somatic point mutations of RET have been described in a subset
      of sporadic medullary thyroid carcinomas (MTCs). We examined tumor and blood DNA
      of thirteen apparently sporadic MTC patients for mutations in RET exons 10, 11,
      13, 15 and 16 to determine whether they had true sporadic tumors or either de
      novo or occult germline mutations. Three different somatic missense mutations
      were documented in seven patients. In five patients a mutation in exon 16, codon
      918, (ATG-->ACG) causing a Met-->Thr substitution was found. In the remaining two
      patients the mutation affected exon 11: codon 630 in one case and codon 634 in
      the other. In both cases a T-->C transversion was identified causing a Cys-->Arg
      substitution. In conclusion, absence of a germline mutation in RET exons 10, 11,
      13 or 16 is evidence against an inherited form in all cases. In seven patients,
      identification of a somatic mutation supported the previous clinical diagnosis of
      sporadic medullary thyroid carcinoma; in one of them we identified a hitherto
      undescribed somatic point mutation at codon 630.

PMID- 9150706
TI  - Improvement of cytochrome P450c17 catalytic processivity as a novel mechanism to
      attenuate hormonal consequences of enzyme decay in the testes after a
      gonadotropin surge.
AB  - OBJECTIVE: The aim of this study was to gain understanding of the apparent
      discrepancy between the moderate restriction of testosterone synthesizing
      capacity and the nearly complete decay of the androgen-producing enzyme,
      cytochrome P450c17 (CYP17; steroid 17 alpha-hydroxylase/17,20-lyase), in rat
      testes during the desensitization phase induced by a single, high-dose
      gonadotropin (human chorionic gonadotropin, hCG) injection. DESIGN AND METHODS:
      Adult male rats received 25 IU hCG i.v., and purified Leydig cells and crude
      interstitial cell microsomes were prepared 0, 4, 12, 24, 48, 72, 120 and 192 h
      afterwards. Component CYP17 activities, i.e. simultaneously catalyzed productive
      androgen formation and abortive 17 alpha-hydroxyprogesterone release, and their
      ratio (processivity), were compared with CYP17 levels and testosterone secretion
      rates. RESULTS: Leydig cells isolated 48 h after the artificial hCG surge produce
      62% less testosterone than control cells upon stimulation in vitro, though CYP17
      levels are reduced by 97%. Its total activity decreases by 87%, resulting in a
      4.5-fold rise in the turnover number; the processivity is additionally improved 5
      fold over controls. Parallel changes occur in interstitial cell microsomes; a
      negative linear correlation exists between the ratio of productive over total
      CYP17 activities and the actual CYP17 concentrations. CYP17 is partly denatured
      to P420 during hCG action, but other heme proteins (cytochrome b5) remain
      unchanged. Animal treatment with estradiol results in CYP17 down-regulation
      without any concomitant effect on enzyme processivity. CONCLUSION: Improved CYP17
      processivity is suggested to be the consequence of (otherwise rate-limiting)
      improved electron transfer efficiency towards CYP17. It explains the relatively
      high testosterone secretion during Leydig cell desensitization and is interpreted
      to be a protective mechanism to confine adverse consequences of enzyme decay.

PMID- 9150705
TI  - Anti-obesity and anti-diabetic effects of CL316,243, a highly specific beta 3
      adrenoceptor agonist, in Otsuka Long-Evans Tokushima Fatty rats: induction of
      uncoupling protein and activation of glucose transporter 4 in white fat.
AB  - The anti-obesity and anti-diabetic effects of a highly specific beta 3
      adrenoceptor agonist, CL316,243 (CL; beta 1: beta 2: beta 3 = 0:1:100,000), were
      investigated in Otsuka Long-Evans Tokushima Fatty (fatty) and Long-Evans
      Tokushima Otsuka (control) rats. Daily injection of CL (0.1 mg/kg, s.c.) to these
      rats (10 weeks old) for 14 weeks caused a significant reduction in body weight
      (fatty, 27%; control, 15%), associated with a marked decrease in fat pad weight
      (inguinal: fatty, 60%; control, 36%; retroperitoneal: fatty, 75%; control, 77%)
      without affecting food intake. The levels of uncoupling protein mRNA and protein
      levels of uncoupling protein (UCP), as well as guanosine 5'-diphosphate-binding
      (a reliable index of thermogenesis) in brown adipose tissue, were lower in the
      fatty than in the control rats. However, after CL treatment, these parameters in
      brown adipose tissue increased significantly 2- to 3-fold in both groups.
      Furthermore, uncoupling protein was induced in white adipose tissue as well as in
      brown adipose tissue. The fatty rats showed hyperglycemia and hyperinsulinemia
      during the glucose tolerance test, but CL ameliorated these parameters. These
      findings suggest that decreased thermogenesis in brown adipose tissue may be one
      of the causes of obesity in the fatty rats and that administration of CL prevents
      obesity by decreasing white fat mass, by activating brown adipose tissue
      thermogenesis, and by inducing uncoupling protein in white adipose tissue.
      Furthermore, CL treatment may inhibit diabetes mellitus by ameliorating obesity
      and by activating glucose transporter 4 in white adipose tissue and brown adipose
      tissue.

PMID- 9150707
TI  - Biosynthesis, processing and sorting of neutrophil proteins: insight into
      neutrophil granule development.
AB  - Neutrophil granulocytes are specialized phagocytic cells that carry a collection
      of granules for regulated secretion, each with distinct constituents. The
      granules can be classified as azurophil (primary), developed first, followed in
      time by specific (secondary) granules gelatinase granules, and secretory
      vesicles. Stage- and tissue-specific transcription factors govern the successive
      expression of genes for granule proteins to allow storage of the gene products in
      these organelle categories whose packaging is separated in time. Many of the
      granule proteins, in particular those of the heterogeneous lysosome-like
      azurophil granules, are subject to extensive post-translational proteolytic
      processing into mature proteins, most commonly as a post-sorting event. A
      selective aggregation of proteins destined for storage in granules, as discussed
      in this review, would facilitate their retention and eliminate a need for
      distinct sorting motifs on each granule protein. Aggregation of granule proteins,
      that are often cationic, would be assisted by the anionic serglycin proteoglycans
      present in neutrophils. The antibacterial granule proteins can serve as models
      for antibiotics and some of them possess a potentially useful therapeutic ability
      to bind and neutralize endotoxin. Because aberrant expression of transcription
      factors regulating the synthesis of granule proteins is often found in leukemia,
      the clarification of mechanisms regulating the timed expression of granule
      proteins will shed light on the maturation block in myeloid leukemias.

PMID- 9150708
TI  - Perioperative use of recombinant human erythropoietin in patients refusing blood
      transfusions. Pathophysiological considerations based on 5 cases.
AB  - The efficacy of the administration of recombinant human erythropoietin (rHuEPO)
      in the treatment of anaemia in critically ill surgical patients refusing red cell
      transfusions requires further documentation. Herein, we report the outcome of 5
      consecutive severely anaemic Jehovah's Witness patients (lowest haemoglobin
      concentration 27 g/1), who were discharged from the hospital in good condition
      after treatment. RHuEPO (50-280 U/kg body weight) was daily administered to 4 of
      the patients, who either exhibited preoperative anaemia or developed
      postoperative anaemia refractory to endogenous EPO probably due to inflammation.
      RHuEPO treatment was followed by a steep rise in reticulocytes and haemoglobin
      concentration. The fifth patient, who exhibited no signs of systemic inflammation
      following emergency hemicolectomy, was also treated with intravenous iron, but
      not with rHuEPO. His blood haemoglobin concentration rose from 27 g/l to 92 g/l
      in 3 wk. These observations indicate that the administration of rHuEPO is
      justified in the management of life-threatening anaemia, although only on a
      humanitarian basis, because there is no predictor for the possible spontaneous
      recovery.

PMID- 9150709
TI  - Iron status in young Danes. Evaluation by serum ferritin and haemoglobin in a
      population survey of 634 individuals aged 14-23 yr.
AB  - Iron status was assessed by serum ferritin and haemoglobin in a population survey
      comprising 634 randomly selected urban Danes (312 males, 322 females) 14-23 yr
      old. At all ages, males had significantly higher serum ferritin and haemoglobin
      values than females. Males: median serum ferritin displayed a steady increase
      with age from 33 to 109 micrograms/l (rs = 0.53, p < 0.0001). The prevalence of
      absent mobilizable body iron stores (serum ferritin < 13 micrograms/l) was 3.5%
      at 16-17 yr of age, gradually declining to 0% at 22-23 yr. None of the males had
      iron deficiency anaemia (serum ferritin < 13 micrograms/l and haemoglobin < 129
      g/l). Females: median ferritin values displayed a slight increase with age from
      28 to 39 micrograms/l (rs = 0.19, p < 0.001). The prevalence of absent iron
      stores was 12.5% at 16-17 yr of age, declining to 6.6% at 22-23 yr. The
      prevalence of iron deficiency anaemia (serum ferritin < 13 micrograms/l and
      haemoglobin < 121 g/l) was 4.7% at 16-17 yr of age, declining to 1.3% at 22-23 yr
      of age. Compared with surveys in other parts of Scandinavia, young Danes had
      slightly higher serum ferritin levels, and a lower prevalence of iron deficiency.

PMID- 9150710
TI  - Assessment of erythropoiesis following renal transplantation.
AB  - Ten patients, who received cadaveric kidneys, were followed for 24 wk with serial
      measurements of serum erythropoietin (S-Epo), transferrin receptor (S-TfR) and
      iron variables. The mean pretransplant creatinine clearance was 8.2 (range 0-22)
      ml/min and the mean haemoglobin (Hb) level was 99 +/- 18.6 (range 66-124) g/l.
      Nine patients demonstrated a gradual increase in S-Epo levels, which reached a
      peak, and was accompanied by a parallel increase in S-TfR levels with a median
      lag period of 3 wk between both peaks. Hb correction followed the S-TfR peak
      after a second lag period (median 7 wk). Elevated S-Epo and S-TfR did not result
      in correction of anaemia in 1 patient due to impaired graft function. Within 4
      months, S-Epo levels reached the normal range while TfR levels were higher than
      normal. Follow-up of iron status demonstrated the development of iron deficiency
      in 5 patients, which was corrected spontaneously. Improvement in erythropoiesis
      after renal transplantation seems to occur by means of expansion of the erythroid
      marrow, as detected by increasing S-TfR levels, subsequent to a S-Epo peak. This
      expansion precedes Hb normalization. A nonuraemic environment is probably a
      prerequisite for the correction of anaemia but not for the increase in S-Epo or S
      TfR levels. Iron deficiency may occur after transplantation due to an increase in
      iron utilization.

PMID- 9150712
TI  - Some correlations between light transmission changes and some commonly used in
      vitro assays for the assessment of platelet concentrates.
AB  - This study aims to relate the duration of light transmission changes (LTCs)
      through platelet concentrates (PCs) to the results of a panel analytical
      procedures, many of which have correlated with platelet in vivo viability. LTCs
      of 16 PCs stored in P1-732 containers were studied over 10 d. On d 1, platelet
      counts and total PC ATP content were determined. On d 7, determination of the
      following parameters was carried out: pH, bicarbonate, the rate of oxygen
      consumption, the dispersion of the size distribution, the total platelet ATP
      content, the extent of shape change (ESC), the osmotic reversal reaction and
      extracellular lactate dehydrogenase (LDH) level. In addition, the rate of lactate
      production was determined over storage. A second series consisting of 18 PCs
      stored in P1-146 containers was monitored over 7 d. Mean platelet volume (MPV)
      was determined on d 3 and 7 and ESC was analysed on d 3. LTCs correlated
      significantly with pH, bicarbonate, the rate of oxygen consumption, increased
      platelet size distribution and decreased ESC. In addition, significant
      correlations were found when comparing LTCs with MPV(s). This study demonstrates
      that LTCs are closely related to parameters reflecting platelet metabolism.

PMID- 9150711
TI  - Amplification of multiple regions of chromosome 12, including 12q13-15, in
      chronic lymphocytic leukaemia.
AB  - Trisomy 12 is a frequent abnormality in chronic lymphocytic leukaemia (CLL). The
      biological importance of trisomy 12 is still poorly understood but it has been
      suggested that one or several genes are duplicated leading to malignant
      transformation. We present a case with amplification of 12q13-22 found in a
      clinically aggressive relapse of CLL. A smaller region, 12q13-15, was amplified
      most frequently and a YAC containing the MDM2 gene gave the highest number of
      signals. Additionally, in a subclone an amplicon containing at least 5 copies of
      a cosmid from 12q23-24 was detected. The case shows that small duplications of
      chromosome 12, not revealed by cytogenetic analysis, may occur in CLL. Also, it
      shows that cytogenetic clonal evolution can occur in CLL without morphological
      evidence of blast transformation. Our results indicate that the 12q13-15 region
      carries an important gene for CLL progression.

PMID- 9150713
TI  - Recovery of drug sensitivity by MS-209, a new multidrug resistance-reversing
      agent, on acute myelogenous leukaemic blasts and K562 cells resistant to
      adriamycin cell line.
AB  - The efficacy of MS-209, a quinoline derivative synthesized as a new multidrug
      resistance (MDR)-reversing agent, was studied on blast cells from 33 acute
      myelogenous leukaemia (AML) patients and on the human myelogenous leukaemia K562
      cell line resistant to adriamycin (K562/ADM). By the addition of MS-209, the
      intracellular daunorubicin (DNR) contents which had been found to be low in P-gp
      positive AML blasts and in K562/ADM were significantly enhanced to the level of P
      gp-negative blasts and that of sensitive K562. The intracellular rhodamine
      (Rh123) contents also increased in P-gp-positive blasts and K562/ADM cells with
      MS-209. A leukaemic blast colony assay also demonstrated the effect of MS-209,
      i.e. a high D10 value for DNR of P-gp-positive blasts was reduced to the D10
      level similar to that observed in P-gp-negative blasts by the addition of MS-209.
      The greater DNR sensitivity reversing effect of MS-209 was observed in blasts
      with higher P-gp positivity. These findings suggest the potential usefulness of
      MS-209 in overcoming MDR in AML patients, especially those with high P-gp
      expression. This study clarified the relationship between the clinical outcome of
      the patients and the P-gp positivity, intracellular DNR content and DNR drug
      sensitivity of leukaemic progenitors.

PMID- 9150714
TI  - Effects of in vivo administration of G-CSF on neutrophil functions in healthy
      volunteers.
AB  - The aim of the present study was to investigate the in vivo effects of
      granulocyte colony-stimulating factor (G-CSF) on neutrophil (PMN) function. G-CSF
      was administered once daily as s.c. injection for 6 d (d1-6) to healthy male
      volunteers. PMN migration (modified Boyden chamber), chemiluminescence (CL),
      adherence to nylon fibers and phagocytosis of IgG- and IgG-C3-coated particles
      were investigated before (d1), during (d2, d5) and 3 wk after G-CSF 7.5-10
      micrograms/kg/d (n = 12). PMN surface expression of adhesion- and Fc gamma
      receptors was measured on d1, d5, d8 and 3 wk after G-CSF 3-5 micrograms/kg (n =
      12). Results obtained after G-CSF were compared to baseline using Wilcoxon's
      signed rank test. G-CSF induced PMNs showed a significantly (p < 0.05) decreased
      chemokinetic response (d5) as well as a reduced chemotaxis towards zymosan
      activated serum, FMLP and IL-8, respectively. Chemotaxis was reduced both at d2
      and d5. Neutrophil adherence, phagocytosis and luminol-enhanced CL increased,
      whereas G-CSF had no effect on lucigenin-enhanced CL. G-CSF (3-5 micrograms/kg)
      caused an enhanced expression of CD11b, CD18, CD35, CD64 (Fc gamma RI) and CD32
      (Fc gamma RII), respectively. We conclude that neutrophils produced in response
      to G-CSF have a reduced chemotaxis but an enhanced adherence and phagocytic
      capacity. G-CSF in vivo does not stimulate the respiratory burst.

PMID- 9150715
TI  - Radiological insertion of long-term indwelling right atrial catheters in
      haematology patients.

PMID- 9150716
TI  - Severe autoimmune hemolytic anemia in hairy cell leukemia.

PMID- 9150717
TI  - Successful treatment of syndrome of inappropriate antidiuretic secretion (SIADH)
      in 2 patients with CNS involvement of chronic lymphocytic leukaemia.

PMID- 9150718
TI  - Markers for the gene ob and serum leptin levels in human morbid obesity.
AB  - Leptin, the product of the ob gene, reduces body fat in genetically obese animals
      and circulates in elevated concentrations in the blood of obese patients.
      Polymorphic markers situated in the proximity of the human ob gene have recently
      been suggested to be linked to morbid obesity. We have studied the possible
      association between the microsatellite markers near the ob gene and morbid
      obesity in 252 morbidly obese patients with a mean body mass index (BMI) of 43 +/
      7 kg/m2, and 151 lean controls with a mean BMI of 22 +/- 2 kg/m2, and searched
      for linkage of these gene markers to obesity in 76 affected sib-pairs (BMI > or =
      32). No significant association was observed between any of the eight
      microsatellite markers and morbid obesity, and affected-sib-pair analysis failed
      to show linkage of three selected ob gene markers to obesity in the sibships.
      There was a strong positive correlation between serum leptin levels and BMI in
      morbidly obese patients; a carrier status for either of the two most prevalent
      alleles of the microsatellite marker D7S530 in the vicinity of the ob gene was
      associated with serum leptin levels in the obese subjects. Two of the markers
      (D7S2519, D7S649) showed a significant relation to the weight-losing response to
      a 16-week very-low-calorie dietary intervention. We have thus been able to
      confirm a tight relationship between serum leptin and body mass but have found no
      evidence for genetic linkage of the ob gene markers to morbid obesity in a
      population considered to represent a genetic isolate and to be an ideal model for
      studies of complex disorders.

PMID- 9150719
TI  - Possible association of the allele status of the CS.7/HhaI polymorphism 5' of the
      CFTR gene with postnatal female survival.
AB  - Cystic fibrosis (CF) patients show a high degree of linkage disequilibrium
      between the CF transmembrane conductance regulator (CFTR) gene and polymorphisms
      5' of that gene. To determine whether the region 5' of CFTR contains biologically
      important sequences, the allele frequencies of six CFTR-linked polymorphisms
      (metH/MspI, XV-2c/TaqI, CS.7/HhaI, KM19/PstI, MP6d9/MspI, J44/XbaI) were
      determined in 417 randomly selected elderly individuals (over 75 years of age)
      from the Czech population. The elderly individuals were considered "escapees" of
      strong selective pressures that had operated during their lifetime, prior to the
      introduction of modern health care since 1950. The pooled allele frequencies of
      the analyzed marker polymorphisms in the elderly did not significantly differ
      from published data. However, when analyzed by ex, the allele frequencies of
      markers CS.7/HhaI and KM19/PstI differed significantly (P < 0.05) between elderly
      females and males. The allele frequencies of the six polymorphisms were then
      determined in 646 newborns and 345 young adults of reproductive age; these
      individuals were selected in a similar manner and drawn from the same population.
      In these control groups, the studied marker polymorphisms exhibited no
      statistically significant differences between sexes and/or between individuals of
      the same sex, only between different age groups. A gradual relative increase in
      the frequency of allele "2" of marker CS.7/HhaI was observed from newborn females
      to elderly women, the overall difference in allele frequencies of this marker
      polymorphism between newborn females and elderly women reaching statistical
      significance (P < 0.05). Interestingly, allele "2" is the major constituent of
      the extended "B-haplotype", which is in strong linkage disequilibrium with common
      CF alleles. Taken together, our data suggest that the region spanning markers
      CS.7 and KM19 is associated with a genetic factor that influences postnatal
      female survival, providing a possible mechanism for increasing the frequency of
      particular mutations in the adjacent CFTR gene.

PMID- 9150720
TI  - Dinucleotide repeat in the 3' flanking region provides a clue to the molecular
      evolution of the Duffy gene.
AB  - The Duffy blood group system consists of three alleles, FYA, FYB, and FY. To
      study the molecular evolution of the three alleles, we established the
      polymorphism of a dinucleotide (GT) repeat sequence (designated FyGT/C) in the 3'
      flanking region of the Duffy gene, and studied the relationship between FyGT/C
      and Duffy polymorphism in Japanese, people of African origin, and chimpanzee. By
      single-strand conformation polymorphism and sequence analysis, five and two
      alleles were identified in Japanese and Africans, respectively. In 110 random
      Japanese, the FyGT/C genotypes observed were in agreement with Hardy-Weinberg
      law. From the sequence of the chimpanzee Duffy gene, including both flanking
      regions, FYB was identified as the ancestral gene of the human alleles. The
      FyGT/C sequences associated with the FY allele of Africans were distinct from
      those of Duffy positives, whereas the FYB and FYA alleles shared common FyGT/C
      sequences. Thus, it is suggested that the first split took place between the FYB
      and FY alleles, and the second between the FYB and FYA alleles.

PMID- 9150721
TI  - The gene for microfibril-associated protein-1 (MFAP1) is located several
      megabases centromeric to FBN1 and is not mutated in Marfan syndrome.
AB  - Linkage studies have mapped the Marfan syndrome (MFS) locus to chromosome region
      15q15-q21 with no convincing evidence of genetic heterogeneity. The fibrillin-1
      (FBN1) gene, located at 15q21.1, that encodes the major component of the
      defective microfibrils, has been identified as the gene for MFS. However,
      extensive mutation screening in many laboratories has detected FBN1 mutations in
      only a fraction of MFS probands studied, leading to the hypothesis that the
      missing mutations could involve another microfibril gene located in the same
      region. Recently, the gene for microfibril-associated protein-1 (MFAP1, also
      called AMP) has been isolated and mapped to the 15q15-q21 region that overlaps
      the location of the FBN1 gene. Here we report that the two loci are physically
      close, making MFAP1 an alternative positional candidate gene for MFS. We have
      carried out MFAP1 mutation screening and gene expression analysis in 48 probands
      with MFS or related phenotypes who were selected for this study because their
      fibroblast cultures synthesized fibrillin at normal levels. No MFAP1 mutations
      were identified, and transcription occurred equally from both alleles. We
      conclude that the MFAP1 locus is not a reservoir for the hidden MFS mutations.

PMID- 9150722
TI  - Exclusion of ZFM1 as a candidate gene for multiple endocrine neoplasia type 1
      (MEN1).
AB  - The multiple endocrine neoplasia type 1 (MEN1) locus has been previously
      localised to 11q13 by combined tumour deletion mapping and linkage studies and a
      3.8-cM region flanked by PYGM and D11S97 has been defined. The zinc finger in the
      MEN1 locus (ZFM1) gene, which has also been mapped to this region, represents a
      candidate gene for MEN1. The ZFM1 gene, which consists of 14 exons, encodes a 623
      amino acid protein and exons 2, 8 and 12 encode the putative nuclear localisation
      signal, a zinc finger motif, and a proline-rich region, respectively. We have
      investigated these potentially functional regions for germ-line mutations by
      single-stranded conformational polymorphism (SSCP) analysis in 64 unrelated MEN1
      patients. In addition, we performed DNA sequence analysis of all the 14 exons and
      13 of the 26 exon-intron boundaries in four unrelated MEN1 patients. A 6-bp
      deletion that resulted in the loss of two proline residues at codons 479 and 480
      in exon 12 was found in one MEN1 patient. However, this did not co-segregate with
      MEN1 in the family and represented a rare polymorphism. Analysis by SSCP, DNA
      sequencing, northern blotting, Southern blotting and pulsed field gel
      electrophoresis revealed no additional genetic abnormalities of ZFM1 in the other
      MEN1 patients. Thus, our results indicate that ZFM1 is excluded as a candidate
      gene for MEN1.

PMID- 9150723
TI  - Alternative splicing of hMSH2 in normal human tissues.
AB  - hMSH2 is a homolog of bacterial mutS and yeast Msh2, a member of the group of
      mismatch repair genes whose products bind to mismatched regions of double
      stranded DNA. We analyzed expression of hMSH2 in normal human organs by the
      polymerase chain reaction coupled with reverse transcription and found two novel
      types of alternatively spliced mRNAs that were expressed in normal human organs.
      One lacked exon 13, and the other lacked a portion from the second nucleotide of
      codon 633 to the second nucleotide of codon 719. In the latter transcript, intro
      12 started with TA and ended with TT (TA-TT intron) which did not meet the GT-AG
      rule. Both types of transcript resulted in frameshifts which generated truncated
      hMSH2 proteins lacking the main part of the highly conserved region. The
      biological significance of the alternative splicing remains to be elucidated.

PMID- 9150724
TI  - Comparative genomic hybridization reveals a partial de novo trisomy 6q23-qter in
      an infant with congenital malformations: delineation of the phenotype.
AB  - We report the use of comparative genomic hybridization (CGH) to define the origin
      of a small extra segment (unidentifiable by classical cytogenetics) present in a
      de novo add(13)q34 chromosome that we found in the karyotype of a newly born boy
      with congenital heart defects, brain anomalies and dysmorphic signs. Initial
      investigation with fluorescence in situ hybridization (FISH) and a chromosome-13
      specific library revealed that the excess material was not derived from
      chromosome 13. To uncover the origin of the unknown chromosome material, CGH was
      carried out on DNA isolated from blood lymphocytes of the patient. By using a
      conventional fluorescence microscope with no digital imaging devices, a single
      distinct region with gain of fluorescent intensity was observed on distal
      chromosome 6q. Confirmation of this finding by FISH with a chromosome-6-specific
      paint and a subtelomeric yeast artificial chromosome clone from 6q26-q27, in
      combination with the band morphology of the small extra chromosomal segment,
      allowed us to diagnose the additional material as being derived from chromosome
      6q23-qter. FISH with a telomere 13q probe detected a terminal deletion of 13q34
      qter on the derivative chromosome 13, indicating that the der(13) was a result of
      a translocation event. Genotyping of the hypervariable apolipoprotein (a) gene,
      which lies within 6q26-q27, showed that the additional chromosome 6 material was
      inherited from the mother. The karyotype of the proposita is therefore: 46,XY,
      13,+der(13)t(6;13)(q23;q34) de novo (mat). Our results confirm the usefulness of
      CGH as an attractive alternative method for the characterization of
      constitutional small genetic imbalances and contribute to the delineation of the
      trisomy 6q23-qter phenotype.

PMID- 9150725
TI  - Trp290Cys mutation in exon IIIa of the fibroblast growth factor receptor 2
      (FGFR2) gene is associated with Pfeiffer syndrome.
AB  - Pfeiffer syndrome is a skeletal disorder characterized by craniosynostosis
      associated with foot and hand anomalies. Mutations in the genes encoding
      fibroblast growth factor receptors 1 and 2 (FGFR1 and FGFR2) have recently been
      implicated in the aetiology of such a syndrome, as well as of other
      craniosynostotic conditions. We now report a novel missense mutation, a G to C
      transversion at position 1049 (exon IIIa) of FGFR2, detected in a patient with
      severe Pfeiffer clinical features. The mutation results in the substitution of a
      cysteine for tryptophan-290 in the third immunoglobulin-like domain and affects
      both spliceoforms of FGFR2. Mutations causing replacement of tryptophan-290 have
      also been reported previously in Crouzon syndrome, a similar but clinically
      distinct craniosynostotic disorder. This finding confirms the involvement of
      mutations of FGFR2 exon IIIa in Pfeiffer syndrome, and emphasizes both the
      extensive heterogeneity of the FGFR2 mutations that result in the Pfeiffer
      phenotype and the perturbations caused by unpaired cysteine residues in receptor
      dimerization and transduction of the FGFs signal.

PMID- 9150726
TI  - The pathogenicity of the Pro1148Ala substitution in the FBN1 gene: causing or
      predisposing to Marfan syndrome and aortic aneurysm, or clinically innocent?
AB  - In individuals with the Marfan syndrome (MFS), mutations have been identified in
      the fibrillin-1 gene (FBN1) at 15q21.1. A proline-to-alanine change at position
      1148 in exon 27 (Pro1148Ala) has been reported in probands with MFS, aortic
      aneurysm or Marfanoid-craniosynostosis. It was suggested that this mutation could
      be a risk factor for aortic dilatation, since it was rarely observed in control
      populations. To investigate further the pathogenicity of this substitution, we
      screened 416 unrelated control individuals by allele-specific oligonucleotide
      (ASO) hybridization. We found 16 individuals who carried the alanine allele
      (3.8%), 3 of whom were homozygous. Five were of Latin American and eight were of
      Asian extraction. We also screened 133 probands with MFS, aortic aneurysm or
      related connective tissue disorders and found 4 (3%) that were heterozygous for
      the 1148Ala allele. All positive results were confirmed by DNA sequencing. In 20
      individuals with 1148Ala, we confirmed the association with the rarer A allele at
      the IVS27-5G-->A polymorphism. Our results suggest that the Pro1148Ala change is
      a polymorphism of ancient evolutionary origin that is more prevalent in Asian and
      Latin American than in Caucasian or African populations.

PMID- 9150727
TI  - Identification of novel mutations in the human EXT1 tumor suppressor gene.
AB  - Hereditary multiple exostoses (EXT) is a genetically heterogeneous bone disorder
      caused by genes segregating on human chromosomes 8, 11, and 19 and designated
      EXT1, EXT2 and EXT3, respectively. Recently, the EXT1 gene has been isolated and
      partially characterized and appears to encode a tumor suppressor gene. We have
      identified six mutations in the human EXT1 gene from six unrelated multiple
      exostoses families segregating for the EXT gene on chromosome 8. One of the
      mutations we detected is the same 1-bp deletion in exon 6 that was previously
      reported in two independent EXT families. The other five mutations, in exons 1,
      6, 9, and the splice junction at the 3' end of exon 2, are novel. In each case,
      the mutation is likely to result in a truncated or nonfunctional EXT1 protein.
      These results corroborate and extend the previous report of mutations in this
      gene in two EXT families, and provide additional support for the EXT1 gene as the
      cause of hereditary multiple exostoses in families showing linkage to chromosome
      8.

PMID- 9150728
TI  - Isolation of a human gene (HES1) with homology to an Escherichia coli and a
      zebrafish protein that maps to chromosome 21q22.3.
AB  - Exon trapping was performed with chromosome 21 cosmids to identify those that may
      be involved in the pathogenesis of Down syndrome, or several of the genetic
      diseases that map to chromosome 21. BLASTX analysis revealed two exons with
      significant homology to a zebrafish protein (ES1) and an Escherichia coli protein
      (sigma cross-reacting protein 27A), both of unknown function. The exons also
      showed identity with several expressed sequence tags (ESTs). Sequences from all
      ESTs derived from this gene and reverse transcription-polymerase chain reaction
      (RT-PCR) analysis were used to determine the full cDNA sequence, which
      corresponded to an mRNA of 1.7 kb with an open reading frame of 268 amino acids.
      The mRNA from this gene, termed HES1, is ubiquitously expressed, but strongly so
      in heart and skeletal muscle. Potential mitochondrial targeting signals were
      found in both the human and zebrafish proteins, consistent with the high
      expression levels in muscle tissues. The strong homology between the E. coli,
      zebrafish and HES1 proteins suggests an important biological role. Hybridization
      of RT-PCR products to a cosmid contig in chromosome 21q22.3, mapped HES1 just
      proximal to D21S25, a critical mapping region for several genetic diseases. Given
      the mapping position, this gene is a candidate for involvement in these
      disorders, including autoimmune polyglandular disease type I and the autosomal
      nonsyndromic deafness loci, DFNB8 and DFNB10. In addition, the initial method of
      EST identification for gene isolation presented here is valid for many genes and
      can be used to obtain initial sequence contigs without cloning or library
      screening.

PMID- 9150729
TI  - Mutations of the CD40 ligand gene in 13 Japanese patients with X-linked hyper-IgM
      syndrome.
AB  - X-linked hyper-IgM syndrome (XHIM) is a rare primary immunodeficiency caused by a
      defective CD40 ligand. We identified mutations of the CD40 ligand gene in 13
      unrelated Japanese XHIM patients. Of the four patients with missense mutations,
      one had a mutation within the transmembrane domain, and the three others had
      mutations affecting the TNF homology region of the extracellular domain. Two of
      the missense mutations resulted in the substitution of amino acids that are
      highly conserved in TNF family proteins. Three patients had nonsense mutations,
      all of which resulted in the truncation of the TNF homology domain of the CD40
      ligand. Three patients had genomic DNA deletions of 2, 3 or 4 nucleotides,
      respectively. All of the deletions were flanked by direct repeat sequences,
      suggesting that these deletions were caused by slipped mispairing. Three patients
      had mutations within introns resulting in altered splicing, and multiple splicing
      products were found in one patient. Thus, each of the 13 Japanese patients had
      different mutations, 9 of them being novel mutations. These results indicate that
      mutations in XHIM are highly heterogeneous, although codon 140 seems to be a hot
      spot of the CD40 ligand gene since two additional point mutations were located at
      Trp 140, bringing the total numbers of mutations affecting codon 140 to six. In
      one XHIM family with a missense mutation, prenatal diagnosis was performed by
      single-strand conformation polymorphism analysis of genomic DNA of a male fetus.

PMID- 9150730
TI  - Carrier and prenatal diagnosis of X-linked severe combined immunodeficiency:
      mutation detection methods and utilization.
AB  - IL2RG, the gene encoding the common gamma chain, gamma c, of the receptor for
      interleukin-2 and other cytokines, has been identified as the disease gene for
      severe combined immunodeficiency (SCID) of the X-linked type. Specific mutational
      diagnosis for X-linked SCID has thus become possible. For many women at risk for
      carrying an IL2RG mutation, no samples were saved from an affected male relative
      prior to either death or bone marrow transplantation (BMT). To establish optimal
      methods for genetic evaluation of such women, we compared mutational screening by
      single-strand conformational polymorphism, heteroduplex analysis and dideoxy
      fingerprinting (ddF). Abnormally migrating band patterns were followed up with
      direct sequencing for identification of specific mutations. The most sensitive
      method, ddF, detected heterozygous alterations, subsequently confirmed to
      represent significant mutations, in all of 19 unrelated obligate or suspected
      carriers studied. Some of these women, as well as others at risk for carrying an
      X-linked SCID mutation, enrolled in a study of prenatal diagnosis after fetal
      testing for gender determination. Originally using linkage analysis and, more
      recently, specific detection of IL2RG mutations, we evaluated pregnancies at risk
      for X-linked SCID prospectively on a research basis. Of 27 male fetuses tested 14
      were predicted to be unaffected and confirmed to have normal immune status at
      birth. Among pregnancies predicted to be affected, 2 were terminated, while 11
      affected males were born at term. Nine of these received neonatal BMT, one had
      BMT at 3 months of age, and one underwent a successful experimental in utero BMT.
      In our study cohort accurate prenatal diagnosis assisted decision making and
      expanded treatment options for families at risk for having infants with a severe,
      but treatable genetic disorder that presents early in life.

PMID- 9150731
TI  - Carbonic anhydrase II (CA II) deficiency in Maghrebian patients: evidence for
      founder effect and genomic recombination at the CA II locus.
AB  - A splice junction mutation at the exon 2-intron 2 boundary of the carbonic
      anhydrase II (CA II) gene was previously shown to be the unique mutation
      underlying the CA II deficiency syndrome in patients of Arab descent. Fourteen
      Tunisian (Maghrebian) families with a history of osteopetrosis, renal tubular
      acidosis, mental retardation, and CA II deficiency were studied to test the
      hypothesis that the mutation, found in all 24 patients, derived from a common
      ancestor originating in the Arabic Peninsula. A filiation study permitted us to
      trace these families back to a common Arabic tribe that settled in the Maghreb in
      the tenth century, indicating a common ethnic origin for these families.
      Segregation of the mutation with a TaqI biallelic restriction site polymorphism
      upstream of the CA II gene was studied by sequence-tagged site analysis in all
      the family members. These studies showed cosegregation of the Taq (-) allele with
      the mutation in 12 families out of 14. This observation supports a founder effect
      to explain the common CA II deficiency allele in this population. In the
      remaining two families, a genomic recombination or gene conversion occurred
      between the TaqI restriction marker and the mutation causing the disease. The
      relatively high recombination frequency suggests the presence of a hot spot for
      recombination or gene conversion at the CA II locus.

PMID- 9150732
TI  - The tricho-rhino-phalangeal syndromes: frequency and parental origin of 8q
      deletions.
AB  - The tricho-rhino-phalangeal syndromes type I (TRPS I) and type II (TRPS II)
      result from the deletion of overlapping sets of genes within the Langer-Giedion
      syndrome chromosomal region (LGCR) on chromosome 8. In contrast to TRPS I
      patients, most TRPS II patients have cytogenetically visible deletions and are
      often mentally retarded. Using Southern blot and fluorescence in situ
      hybridization analysis, we searched for submicroscopic deletions in 12 patients
      with TRPS I and an apparently normal karyotype. One patient of normal
      intelligence was found to have a deletion of approximately 5 Mb. This suggests
      that mental retardation in TRPS is caused by genes outside the 5-Mb region. Using
      three LGCR microsatellite markers, we determined the parental origin of this TRPS
      I deletion and of eight TRPS II deletions. In six patients, the deletion was of
      paternal origin and in three patients it was of maternal origin.

PMID- 9150733
TI  - New amino acid polymorphism, Ala/Val4058, in exon 45 of the polycystic kidney
      disease 1 gene: evolution of alleles.
AB  - The PKD1 gene, which is responsible for the most common form of autosomal
      dominant polycystic kidney disease, has recently been cloned and sequenced. Many
      disease-causing mutations have been characterized in this gene, most of them
      resulting in premature protein termination. However, mutation analysis not
      routinely implemented for family investigations in a clinical setting, because of
      the large size and complexity of the gene. Instead, genetic linkage analysis
      using highly polymorphic CA dinucleotide repeats that map around the gene is
      still the method of choice. Recently, a few intragenic polymorphisms have been
      described that are also useful for linkage studies. Here, a new diallelic
      polymorphism is described for amino acid residue 4058, Ala/Val4058, with allelic
      frequencies of 0.88 and 0.12, respectively, and a heterozygosity of 0.23, in the
      Greek and Greek-Cypriot populations. Interestingly, this polymorphism and Ala4091
      A/G, which has previously been described in Caucasians, were not detected in DNA
      from 44 Japanese samples tested. This is particularly important when allelic
      frequencies in a particular population are used for linkage analysis of families
      of different ethnic origin. Also, observation of the two polymorphisms together
      as haplotypes suggests that the Ala/Val4058 polymorphism occurred more recently
      than the establishment of the Ala4091-A/G polymorphism, and specifically on the G
      allele.

PMID- 9150734
TI  - Mutations and sequence variants in the testis-determining region of the Y
      chromosome in individuals with a 46,XY female phenotype.
AB  - The testis-determining gene SRY (sex determining region, Y) is located on the
      short arm of the Y chromosome and consists of a single exon, the central third of
      which is predicted to encode a conserved motif with DNA binding/bending
      properties. We describe the screening of 26 patients who presented with 46,XY
      partial or complete gonadal dysgenesis for mutations in both the SRY open reading
      frame (ORF) and in 3.8 kb of Y-specific flanking sequences. DNA samples were
      screened by using the fluorescence-assisted mismatch analysis (FAMA) method. In
      two patients, de novo mutations causing complete gonadal dysgenesis were detected
      in the SRY ORF. One was a nonsense mutation 5' to the HMG box, whereas the other
      was a missense substitution located at the C terminus of the conserved motif and
      identical to one previously detected in an unrelated patient. In addition, two Y
      specific polymorphisms were found 5' to the SRY gene, and a sequence variant was
      identified 3' to the SRY polyadenylation site. No duplications of the DSS region
      in 20 of these patients were detected.

PMID- 9150735
TI  - Identification of a modifier gene locus on chromosome 1p35-36 in familial
      adenomatous polyposis.
AB  - Phenotypic variability based on nonallelic heterogeneity is a characteristic
      feature of the dominantly inherited disease, familial adenomatous polyposis
      (FAP). A modifying locus, called Mom-1, which strongly influences disease
      expression has been mapped in the mouse model of FAP to the region of murine
      chromosome 4, which has synteny to human chromosome 1p35-36. In the present
      study, this chromosomal region was investigated by using 14 microsatellite
      markers within a large FAP kindred in which patients harbor the same germ-line
      mutation but show markedly different disease characteristics. The linkage program
      MLINK was used to determine whether any correlation exists between these markers
      and the development of extracolonic symptoms in polyposis coli patients.
      Depending on the mode of inheritance of the affected locus, a maximum lod score
      was observed for markers D1S211 and D1S197, reaching 2.08 and 1.77, respectively.
      The observed values obtained within one large FAP family are supportive of a
      phenotype-modifying locus within this chromosomal region.

PMID- 9150736
TI  - A small intraexonic deletion within the dystrophin gene suggests a possible
      mechanism of mutagenesis.
AB  - A case of Duchenne muscular dystrophy is described with an unusual mutation
      consisting of a 17-bp deletion within exon 47 of the dystrophin gene. The
      sequences on either side of the deletion have a high degree of intrastrand base
      complementarity. It is hypothesised that the mechanism generating the deletion
      may have been the formation of hairpin loop structure in a single strand of DNA
      followed by enzymatic degradation at unpaired regions within the loop.

PMID- 9150737
TI  - Lack of association between five polymorphisms in the human glucocorticoid
      receptor gene and glucocorticoid resistance.
AB  - Glucocorticoid resistance due to mutations in the gene for the glucocorticoid
      receptor has been suggested to be more common than is thought at present, owing
      to the relative mildness of its symptoms and the difficulty of its diagnosis. To
      investigate the prevalence of mutations in the glucocorticoid receptor gene
      responsible for relative insensitivity to glucocorticoids, we carried out
      polymerase chain reaction/single-strand conformation analysis of the
      glucocorticoid receptor gene in a group of 20, otherwise healthy, persons with a
      reduced response in a dexamethasone suppression test and in 20 controls. We did
      not find mutations or polymorphisms associated with a reduced sensitivity to
      glucocorticoids. However, we identified five novel polymorphisms in the gene for
      the human glucocorticoid receptor, which may be useful in analyzing whether loss
      of (part of) the glucocorticoid receptor gene plays a role in glucocorticoid
      resistant malignancies. Although relative resistance to glucocorticoids seems to
      be rather frequent in otherwise healthy persons, it is not usually associated
      with mutations or polymorphisms in the glucocorticoid receptor gene.

PMID- 9150738
TI  - Hb Lepore-Baltimore (delta 68Leu-beta 84Thr) and Hb Lepore-Washington-Boston
      (delta 87Gln-beta IVS-II-8) in central Portugal and Spanish Alta Extremadura.
AB  - Hb Lepore is one of the most common abnormal haemoglobins in Caucasians in
      Central Portugal and in the Spanish Alta Extremadura (0.28% in a survey of school
      children). A group of 19 Portuguese and 14 Spanish Hb Lepore carriers (all
      unrelated) was characterised at the molecular level by the polymerase chain
      reaction, sequencing and restriction enzyme analysis. The Portuguese and one
      Spanish carrier were heterozygous for Hb Lepore-Baltimore, whereas all other
      Spanish subjects were Hb Lepore-Washington-Boston carriers. Sequencing of the Hb
      Lepore-Baltimore gene further established the crossover at delta 68-beta 84, a
      region two codons (CDs) shorter than that previously described and easily
      confirmed by digestion with MaeI and BanI. Data from haplotype analysis suggest
      that this crossover occurred as an independent event on the Iberian Peninsula.
      The haematological data were similar in both groups except for the levels of Hb F
      and the G gamma chain, which were significantly higher in the Hb Lepore-Baltimore
      heterozygotes. Quantification of the globin chains and the mRNA transcripts
      showed that the delta beta gene is transcribed at a higher level than the delta
      gene with levels of translation giving rise to 10%-15% of Hb Lepore. The
      different levels of Hb F observed in the two groups are the results of the higher
      transcription rate of the gamma genes in Hb Lepore-Baltimore heterozygotes and an
      apparently less efficient translation of G gamma genes in Hb Lepore-Washington
      Boston heterozygotes.

PMID- 9150739
TI  - Characterization and significance of nine novel mutations in exon 16 of the
      neurofibromatosis type 1 (NF1) gene.
AB  - Nine novel mutations have been characterized as the result of screening exon 16
      of the human NF1 gene in 465 unrelated neurofibromatosis type 1 patients. These
      lesions include three nonsense and two missense mutations, two deletions, one
      duplication, and one mutation in the 5' splice site of intron 16. Although exon
      16 is the largest NF1 exon, no mutations have so far been reported in this
      region. This apparent paucity of lesions may be due either to a reduced
      functional importance of exon 16 or a screening bias or both. However,
      consideration of the mutability of exon 16 in comparison with other exons
      suggests that, at least for single base pair substitutions, no such factors need
      be invoked. Any previous lack of exon 16 mutations in this category would be
      explicable in terms of a lower propensity to mutate for codons in this gene
      region.

PMID- 9150740
TI  - B-cell-negative severe combined immunodeficiency associated with a common gamma
      chain mutation.
AB  - Severe combined immunodeficiency (SCID) is caused by a variety of underlying
      defects. Approximately 40% of cases are thought to be of the X-linked type
      (SCIDX1), which is phenotypically characterised by the absence, or very low
      numbers, of T cells, but normal or even high B cell numbers. The gene responsible
      for SCIDX1 is that coding for the common gamma chain (gamma c), a component of
      multiple cytokine receptors. Mutations in this gene have been demonstrated in a
      large number of boys affected by typical SCIDX1. We describe a sporadic case of a
      boy who had SCID with absent B cells and absent T cells, but in whom a mutation
      in the gamma c gene has been demonstrated. In the absence of a typical X-linked
      pedigree, the phenotype in this boy suggested an autosomal recessive form of SCID
      and the family would usually have been counselled accordingly. This family raises
      the question of the true frequency of SCIDX1 amongst sporadic male cases of SCID
      and highlights the need to screen these boys for gamma chain mutations.

PMID- 9150741
TI  - Common ancestry of three Ashkenazi-American families with Alport syndrome and
      COL4A5 R1677Q.
AB  - Mutations in the basement membrane collagen gene COL4A5 cause the progressive
      renal glomerular nephropathy and typical hearing loss that occur in X-linked
      Alport syndrome. Nearly all cases involve distinct mutations, as expected for an
      X-linked disease that significantly reduces the fitness of affected males. A few
      exceptional COL4A5 mutations appear to be associated with a reduced disease
      severity and may account for a significant proportion of late-onset Alport
      syndrome in populations where a founder effect has occurred. The novel mutation
      reported here, COL4A5 arg1677gln, has been detected in three independently
      ascertained Ashkenazi-American families, causes a relatively mild form of
      nephritis with typical onset in the fourth or fifth decade, and may be involved
      in the etiology of a large proportion of adult-onset hereditary nephritis in
      Ashkenazi Jews.

PMID- 9150742
TI  - Refinement of the hereditary neuralgic amyotrophy (HNA) locus to chromosome 17q24
      q25.
AB  - Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant, recurrent focal
      neuropathy characterized by episodes of painful brachial plexus neuropathy with
      muscle weakness and atrophy, as well as sensory disturbances. Single episodes are
      commonly preceded by unspecific infections or immunization, or are associated
      with parturition. Minor facial dysmorphic features are present in some pedigrees
      but do not clearly segregate with the disease. To confirm the recently described
      HNA locus on distal chromosome 17q, we performed a genetic linkage study in an
      extended Turkish pedigree. We were able to refine the HNA locus on chromosome
      17q24-q25 in a 16-cM region.

PMID- 9150743
TI  - Polymorphisms in the PMP-22 gene region (17p11.2-12) are crucial for simplified
      diagnosis of duplications/deletions.
AB  - DNA duplications and deletions of a 1.5-Mb region in chromosome 17p11.2-12
      comprising the gene encoding peripheral myelin protein 22 (PMP-22) are the common
      mutations in Charcot-Marie-Tooth disease type 1 (CMT1) and hereditary neuropathy
      with liability to pressure palsies (HNPP). A 1.7-kb recombination hotspot region
      has been identified within misaligned flanking repeats (CMT1-REP elements) by
      detection of CMT- and HNPP-specific junction fragments in Southern blot analyses.
      In order to simplify routine diagnosis we introduce a polymerase chain reaction
      based method to identify directly specific REP junction fragments. Using this
      test, specific fragments were detected in approximately 67% of both CMT
      duplication and HNPP deletion cases. Polymorphism within a specific restriction
      enzyme recognition site is crucial for both Southern blot and PCR analyses of
      junction fragments.

PMID- 9150744
TI  - Identification of an HD patient with a (CAG)180 repeat expansion and the
      propagation of highly expanded CAG repeats in lambda phage.
AB  - The Huntington's disease mutation has been identified as a CAG/polyglutamine
      repeat expansion in a large gene of unknown function. In order to develop the
      transgenic systems necessary to uncover the molecular pathology of this disorder,
      it is necessary to be able to manipulate highly expanded CAG repeats in a cloned
      form. We have identified a patient with an expanded allele of greater than 170
      repeat units and have cloned the mutant allele in the lambda zap vector. The
      recovery of highly expanded repeats after clone propagation was more efficient
      when repeats were maintained as lambda phage clones rather than as the plasmid
      counterparts. Manipulation of the repeats as phage clones has enabled us to
      generate Huntington's disease transgenic mice that contain highly expanded
      (CAG)115-(CAG)150 repeats and that develop a progressive neurological phenotype.

PMID- 9150745
TI  - Mermaid: a not-so-new family of human repetitive elements.

PMID- 9150746
TI  - Cycling-PRINS. A method to improve the accuracy of telomeric sequence detection
      in mammalian chromosomes.
AB  - The presence of (TTAGGG)n telomeric sequence was investigated in a Chinese
      hamster tumor-derived cell line, using single primed in situ labelling (single
      PRINS) and multiple cycles of amplification (cycling-PRINS). The telomeric
      sequence hybridized the centromere of most chromosomes, using both techniques.
      However, signals visible at the telomeric regions of some chromosomes and an
      enhancement of the frequency signals at the centromere of chromosome 1 were
      obtained using cycling-PRINS. These results indicate that cycling-PRINS
      represents a promising improvement for detection of telomeric sequence in cell
      lines where the conventional methods failed to demonstrate their presence.

PMID- 9150747
TI  - Human chromosome aberrations induced in vitro by Paracoccidioides brasiliensis
      glycoproteic component (GP 43).
AB  - The in vitro cytogenetic effects of the 43-kDa molecular mass exocellular
      glycoproteic component (GP 43) from Paracoccidioides brasiliensis were studied in
      cultures from human lymphocytes. The sample included 10 healthy, white, non
      smoking, non-related males (mean age of 31.3 +/- 8.2 years). Besides the control,
      three concentrations of GP 43 (0.125, 1.25 and 5 micrograms/ml) were used. In
      each group, around 1000 cells were examined in search of chromosome aberrations,
      and 30000 metaphases were analysed for the determination of the Mitotic Index.
      The authors conclude that GP 43 most probably causes inhibition of the cell cycle
      and aneugenic and clastogenic effects.

PMID- 9150748
TI  - Genotoxicity of ethyl carbamate (urethane) in Salmonella, yeast and human
      lymphoblastoid cells.
AB  - Ethyl carbamate is a known carcinogen occurring in fermented food and beverages
      and is therefore of interest for food safety assurance. We studied the
      genotoxicity of ethyl carbamate in Salmonella typhimurium, in Saccharomyces
      cerevisiae and in human lymphoblastoid TK6 cells. In absence of cytochrome P450
      enzymes, no ethyl carbamate-mediated genotoxicity was observed in any of the
      three test systems in the non-cytotoxic range. In the presence of an activating
      system, ethyl carbamate was found to be mutagenic in Salmonella typhimurium
      strain TA100 but not in strains TA98 and TA102, indicating base-pair
      substitutions at G-C base pairs. In contrast, no significant mutagenicity of
      ethyl carbamate could be detected in human lymphoblastoid TK6 cells. However,
      applied in cytotoxic concentrations, ethyl carbamate was genotoxic for
      Saccharomyces cerevisiae in the absence of P450-mediated metabolic activation.
      Inhibitors of P450IIE1 (DMSO, ethanol and dithiodiethylcarbamate) diminished
      ethyl carbamate-mediated mutagenicity in Salmonella typhimurium strain TA100 in a
      dose dependent manner, suggesting that P450IIE1 is the activating enzyme.

PMID- 9150749
TI  - Interference with microtubules and induction of micronuclei in vitro by various
      bisphenols.
AB  - Bisphenols, in particular bisphenol-A (BP-A), are monomers of various plastics
      including polycarbonates and epoxy resins which are used in numerous consumer
      products. The release of BP-A from some of these materials has recently been
      reported. BP-A is a weak estrogen and structurally related to the aneuploidogenic
      stilbene estrogen diethylstilbestrol (DES). We have therefore studied BP-A and
      four other bisphenols for their aneuploidogenic potential by assaying their (i)
      interference with the cell-free assembly of microtubules (MT); (ii) disruption of
      the cytoplasmic MT complex in cultured Chinese hamster V79 cells; (iii)
      disruption of the mitotic spindle and induction of metaphase arrest in V79 cells;
      and (iv) induction of micronuclei (MN) in V79 cells. At concentrations without
      gross cytotoxicity, BP-A as well as its alkyl-fluorinated and ring-methylated
      analog were active at all endpoints tested, whereas the bisphenol without alkyl
      groups was completely inactive. 4,4'-Dihydroxybenzophenone was inactive against
      cell-free and cytoplasmic MT but disrupted the mitotic spindle and induced
      metaphase arrest and MN. The MN caused by the various bisphenols were analyzed
      for the presence of kinetochores by staining with CREST antibodies. All induced
      MN were CREST-positive, implying that they contain whole chromosomes/chromatids.
      The effects on MT and the induction of metaphase arrest and of CREST-positive MN
      suggest that the environmental estrogen BP-A and some of its analogs are
      potential aneuploidogens.

PMID- 9150750
TI  - Detection of micronuclei in gill cells and haemocytes of mussels exposed to
      benzo[a]pyrene.
AB  - Mediterranean mussels were exposed to benzo[a]pyrene for 2 days at doses which
      had previously caused the formation of specific adducts in gill DNA. Micronuclei
      and other nuclear abnormalities were detected in gill cells and haemocytes in
      order to ascertain the induction of cytogenetic damage in two different target
      cells in parallel. A number of procedural details were examined initially to
      improve the quality of slides obtained from mussel cells. Adequate cytological
      preparations were obtained when gill cells and haemocytes were suspended,
      respectively, in Alsever and sea water with EDTA, cytospun and fixed with
      absolute methanol. In the exposed mussels, micronuclei significantly increased in
      both the large gill cells (the main cell type) and the agranular haemocytes.
      Granular haemocytes, cells present in variable proportions between individual
      mussels, did not show cytogenetic damage except at the highest B[a]P doses. In
      the same slides, steady levels of binucleated cells were detected, whereas the
      incidence of other nuclear abnormalities was significantly higher in the exposed
      compared with control mussels. Precise knowledge of the replication kinetics of
      gill cells and haemocytes is still lacking.

PMID- 9150751
TI  - Formation of 8-hydroxy-2'-deoxyguanosine following treatment of 2'-deoxyguanosine
      or DNA by hydrogen peroxide or glutathione.
AB  - We have demonstrated that free radicals generated by hydrogen peroxide (H2O2), in
      the presence of divalent iron (Fe2+) and a chelator (EDTA), oxidize 2'
      deoxyguanosine (dG) to 8-hydroxy-2'-deoxyguanosine (8-OHdG). The 8-OHdG formed by
      this reaction was isolated and quantitated using reverse-phase HPLC with UV and
      electrochemical detection. A 1-h incubation of dG with H2O2 caused a 50% increase
      in 8-OHdG over background, which increased to 100% after 2 h. However, when an
      H2O2-generating system [glutathione (GSH), Fe2+, EDTA] was used, there was no
      increase in 8-OHdG yield after the 1-h incubation, but up to a 50% increase over
      background was observed with GSH after 2-h incubation. Attempts to detect
      increased levels of 8-OHdG after H2O2- or GSH-treatment of purified calf thymus
      or rat DNA, or purified Salmonella typhimurium DNA were not successful. This may
      have been because the treatment procedures used generated 8-OHdG in the control
      samples at sufficiently high levels to mask any H2O2-induced responses that may
      have been present. This artifactual production of 8-OHdG has presented a problem
      in all in vitro studies to date. In contrast, treatment of Salmonella cells
      (strain TA104) with increasing concentrations of H2O2, caused a doubling in the 8
      OHdG yield. GSH-treatment of strain TA104 cells under the same conditions did not
      result in an increase of 8-OHdG. The study presented here shows that the
      ubiquitous molecule H2O2 can play a major role in DNA oxidation, mutation, and
      damage.

PMID- 9150752
TI  - An in vivo micronucleus assay for detecting the clastogenic effect in rat kidney
      cells.
AB  - A micronucleus assay in vivo has been developed that is based on the use of
      freshly isolated kidney cells from mononephrectomized rats. In this validation
      study, a statistically significant increase in the frequency of micronucleated
      cells was detected in rats given i.p. a single dose of four kidney carcinogens, N
      nitrosodimethylamine, N-nitrosodiethylamine, N-ethyl-N-hydroxyethylnitrosamine
      and N-nitroso-N-methylurea. The clastogenic effect was more marked when the same
      dose was injected for 3 successive days. As compared to controls, treated rats
      displayed a reduction in the frequency of binucleated cells, presumably due to a
      toxicity-induced inhibition of cellular proliferation. The proposed method should
      be suitable for the detection of the clastogenic effect of procarcinogens
      biotransformed into reactive species in the kidney.

PMID- 9150753
TI  - DNA adducts in human placenta as related to air pollution and to GSTM1 genotype.
AB  - DNA adducts in human placenta have been studied in relation to metabolic genotype
      for glutathione S-transferase M1 (GSTM1) in 98 mothers living in two regions with
      a different annual average air pollution levels: Northern Bohemia-the district of
      Teplice as polluted industrial area (mines, brown coal power plants) and Southern
      Bohemia-the district of Prachatice as agricultural area without heavy industry.
      Forty-nine placenta samples (25 from the Teplice district and 24 from the
      Prachatice district) from non-smoking mothers with the date of delivery in the
      summer period and 49 placenta samples (25 from the Teplice district and 24 from
      Prachatice district) from mothers with the date of delivery in the winter period
      were analysed. The total DNA adduct levels were calculated as the sum of adducts
      in the diagnoal radioactive zone (DRZ) and one distinct spot outside of the DRZ
      (termed X), which was detected in almost all placenta samples. We found total DNA
      adduct levels of 1.40 +/- 0.87 (0.04-3.65) and 1.04 +/- 0.63 (0.11-3.08) adducts
      per 10(8) nucleotides for the Teplice and Prachatice districts, respectively. The
      significant difference between both districts in placental DNA adduct levels was
      found for the winter sampling period only (1.49 vs. 0.96 adducts per 10(8)
      nucleotides; p = 0.023). No seasonal variation was observed for DNA adduct levels
      in the overall population studied. A positive GSTM1 genotype was detected in 51
      subjects, while GSTM1-null genotype was found in 47 subjects. Higher DNA adduct
      levels were detected in a group with GSTM1-null genotype (p = 0.009). This
      finding seems more significant for subjects in the Teplice district (p = 0.047)
      than for those in the Prachatice district (p = 0.092). Significant district and
      seasonal differences were found in subgroups carrying the GSTM1-null genotype.
      DNA adduct levels in placentas of mothers with GSTM1-null genotype living in the
      polluted district of Teplice were higher than those in Prachatice (p = 0.050);
      also the adduct levels in placentas sampled in the summer period were higher than
      those sampled in the winter period (p = 0.011). Our results indicate that
      simultaneous analysis of DNA adducts and metabolic genotypes could emphasize the
      use of DNA adduct measurements, particularly in the case of the environmental
      exposure when the total doses of genotoxic pollutants are very low.

PMID- 9150754
TI  - The use of the same image analysis system to detect genetic damage in human
      lymphocytes treated with doxorubicin in the Comet and fluoresence in situ
      hybridisation (FISH) assays.
AB  - Two assays, the alkaline single cell gel electrophoresis (Comet) assay and the
      fluorescence in situ hybridisation (FISH) of a whole chromosome or 'chromosome
      painting' assay have gained importance in recent years as witnessed by the
      increasing yield of scientific literature using these techniques. Thus, it would
      be useful to have one system to measure both endpoints. In the present
      communication, a cost-effective electronic imaging system developed by Kinetic
      Imaging Ltd., UK, has been used to measure, after treatment of human lymphocytes
      with doxorubicin, DNA damage in the Comet assay (using software package KOMET)
      and chromosome damage with the FISH technique (using software package KROMASCAN).
      The chromosome damage has been detected using chromoprobe-M for chromosome 1 and
      compared with chromosome damage measured using the conventional Giemsa staining
      technique. In all three assays, cycling cells were treated, after
      phytohaemagglutinin stimulation, at 48 h for about 20 h, which resulted in
      statistically significant dose-related responses in each assay. In non-cycling
      cells there was no increase in damage in the Comet assay, but there was in the
      chromosome assays. The FISH assay was only conducted in cycling cells, since the
      probe used was metaphase-specific. At the highest doses of doxorubicin used, FISH
      and conventional chromosome assays had similar sensitivities.

PMID- 9150755
TI  - High body temperature induces micronuclei in mouse bone marrow.
AB  - The mouse micronucleus test was conducted to investigate the effect of high body
      temperature on micronucleus induction. Group of 10 male ddY mice were exposed to
      30 degrees C for 1, 3 or 6 h, 37 degrees C for 0.5, 1, 2, 3 or 4 h, and 40
      degrees C for 1 or 2 h. Bone marrow cells were sampled 24 h after heat exposure.
      Exposure of mice to 37 degrees C for 3 or 4 h and 40 degrees C for 1 or 2 h
      raised body temperature to approximately 40.5 degrees C and produced
      statistically significant increases in micronucleated polychromatic erythrocyte
      frequencies (8.1 +/- 4.5, 6.0 +/- 2.1, 5.3 +/- 3.3, 7.5 +/- 2.9%, respectively;
      control frequencies, 2.0 +/- 1.1%). In addition, about 25% of the induced
      micronuclei were relatively large (diameter of micronucleus > or = 1/4 diameter
      of cytoplasm). These results suggest that body temperatures of 39.5 degrees C or
      higher for more than 30 min induce micronuclei in bone marrow cells, and one
      possible mechanism is disturbance of the mitotic apparatus.

PMID- 9150756
TI  - Mutation induction and mutation frequency decline in halogen light-irradiated
      Escherichia coli K-12 AB1157 strains.
AB  - The effects of halogen light irradiation on reversion of argE3-->Arg+ in E. coli
      K12 strain AB1157 and its mfd- mutant, and on mutation frequency decline (MFD)
      after transiently incubating irradiated bacteria under non-growing conditions
      were studied. The induction of mutations, the mutational specificity, and the MFD
      effect had the same characteristic features as those seen in E. coli B strains
      after irradiation with 254 nm UV light. MFD which is due to repair of
      premutagenic lesion in the transcribed strand of glnU gene and prevents mutations
      leading to supB formation, was not observed in halogen light-induced mutations in
      the mfd-1 strain. Overproduction of UmuD'C proteins led to a large increase in
      mutation frequency, which was much greater in mfd- than in mfd+ strains. In
      bacteria irradiated with halogen light and incubated immediately in a rich medium
      to express mutations, the formation of supB predominated strongly over that of
      supE(ochre) in mfd- cells but was at a similar level in mfd+ cells. Introduction
      of zcf117::Tn10 to AB1157 strain makes cells more sensitive to halogen light
      irradiation, whereas introduction of mfd-1 does not.

PMID- 9150757
TI  - Differential effect of acetyltransferase expression on the genotoxicity of
      heterocyclic amines in CHO cells.
AB  - We earlier developed the Chinese hamster ovary UV5P3 cell line that expresses
      cytochrome P4501A2 and lacks nucleotide excision repair for studying metabolism
      and mutagenicity of heterocyclic amines. The Chinese hamster ovary UV5P3 cells
      are approximately 50-fold more sensitive to the cooked food mutagen, 2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) than 2-amino-3-methylimidazo[4,5
      f]quinoline (IQ), another genotoxic compound found in cooked food, with respect
      to cytotoxicity and mutation induction at the adenine phosphoribosyltransferase
      (aprt) locus. To test the hypothesis that the important missing activity in our
      CHO system for IQ genotoxicity was acetyltransferase, we transfected the UV5P3
      cells with cDNA plasmids of either the human NAT2 N-acetyltransferase gene or a
      bacterial O-acetyltransferase gene. Functionally transformed clones were
      determined by the differential cytotoxicity assay using IQ, and confirmed by
      measuring the enzyme activity with isoniazid as substrate. Two clones designated
      5P3NAT2 and 5P3YG (expressing human and bacterial transferases, respectively)
      were characterized. Both cell lines were sensitive to killing by IQ at
      concentrations as low as 4 ng/ml. Based on the D37 value, the dose that reduced
      the survival to 37% relative to untreated controls, the acetyltransferase
      expressing lines showed approximately 1000-fold increase in sensitivity to the
      killing effect of IQ over the parental UV5P3 cell line. The same dramatic change
      in sensitivity was also seen in mutation response at the aprt locus and with
      chromosomal aberrations and sister chromatid exchanges. In contrast, these cell
      lines showed cytotoxicity to PhIP similar to that of the parental line UV5P3.
      These results suggest that PhIP does not require acetyltransferase for metabolic
      activation leading to genotoxicity in these cells. These new cell lines
      constitute a sensitive cell system for assessing genotoxicity of compounds
      requiring metabolic activation by both P450IA2 and acetyltransferase, as well as
      for studying the molecular processes by which DNA damage can lead to mutation and
      cancer.

PMID- 9150758
TI  - Cytogenetic effects of softwood kraft pulp bleaching effluents and
      methanesulfonyl chloride in Chinese hamster ovary cells.
AB  - The genotoxicity of effluents collected from a conventional 5-stage softwood
      kraft pulp bleaching process was studied in Chinese hamster ovary (CHO) cells in
      vitro. Spent liquor from the first chlorination stage (C/D), where elemental
      chlorine and chlorine dioxide had been used in equal proportions, was shown to
      induce a dose-dependent increase in sister chromatid exchanges (SCEs) without
      metabolic activation (4-h treatment), with a maximum increase of 1.6 times over
      the control level at 204 microliters/ml; this dose also induced 15.5- and 20.5
      fold increases in cells with chromatid-type chromosomal aberrations after 4-h and
      a 20-h treatment, respectively. Another C/D stage spent liquor from a process
      where the ratio of elemental chlorine and chlorine dioxide had been 9:1 produced
      a 40.5-fold elevation of cells with chromatid-type aberrations at 204
      microliters/ml (20-h treatment). This sample clearly increased chromosomal
      aberrations also when tested as a concentrate (4-h treatment), which showed that
      the observed clastogenicity was not unspecifically due to the relatively large
      volumes used in the treatments with the unconcentrated liquors. In general, the
      use of rat liver S9 mix reduced the genotoxicity of the spent liquors. The
      results agree with earlier findings on the Salmonella mutagenicity of the same
      C/D samples: both the prokaryotic and eukaryotic assays showed a reduction in
      genotoxicity when the amount of elemental chlorine in the bleaching process was
      reduced. An effluent sample collected from the alkaline stage of the process was
      not clastogenic with or without metabolic activation. Methanesulfonyl chloride, a
      new compound identified in bleaching plant air, was found to be induce
      chromosomal aberrations in the presence of S9 mix.

PMID- 9150759
TI  - Modulation of mitomycin C mutagenicity on Saccharomyces cerevisiae by
      glutathione, cytochrome P-450, and mitochondria interactions.
AB  - It is well established that most anticancer drugs also have mutagenic effects and
      require metabolic activation before exerting their mutagenic/antiblastic
      activity. Antitumoral compound effects strongly depend on the
      biochemical/physiological conditions of the tumoral cells, and especially on the
      activation of specific drugs metabolizing enzymes and on respiration. We examined
      the mitomycin C-induced mutagenic effects on the D7 strain of Saccharomyces
      cerevisiae and on its derivative mitochondrial mutant p degrees at different
      contents of glutathione and cytochrome P-450, molecules able to
      activate/detoxicate xenobiotics. The mutagenic activity of the drug was evaluated
      as frequency of mitotic gene conversion and reversion in different physiological
      conditions. The highest frequencies of reversion and especially of gene
      conversion were observed at the highest cytochrome P-450 contents in the D7
      strain with a further increase at high glutathione level. In the respiratory
      deficient strain, the highest frequency of convertants was shown at low
      glutathione level and lack of cytochrome P-450. These results suggest the
      relevance of mitochondrial functionality for the expression of genotoxic activity
      of this anticancer drug.

PMID- 9150760
TI  - Allium cepa anaphase-telophase root tip chromosome aberration assay on N-methyl-N
      nitrosourea, maleic hydrazide, sodium azide, and ethyl methanesulfonate.
AB  - The Allium anaphase-telophase assay was used to show genotoxicity of N-methyl-N
      nitrosourea (MNU), maleic hydrazide (MH), sodium azide (NaN3) and ethyl
      methanesulfonate (EMS). All agents induced chromosome aberrations at
      statistically significant levels. The rank of the lowest doses with positive
      effect was as follows: NaN3 0.3 mg/l < MH 1 mg/l < MNU 41 mg/l < EMS 100 mg/l.
      The results were compared with results from other plant assays (Arabidopsis,
      Vicia, Tradescantia) and for MH and MNU the values were found to be within the
      same range, whereas the results in the Allium test for NaN3 and EMS were in a
      lower range than that found for the other plant assays. EMS and MMS (methyl
      methanesulfonate), two chemicals used as positive controls in mutagenicity
      testing, were compared in the Allium test, and MMS was found to be about ten
      times more potent in inducing chromosome aberrations than EMS. Recording of
      micronuclei in interphase cells showed that this endpoint does not give more
      information of clastogenicity than recording of chromosome aberrations in
      anaphase-telophase cells.

PMID- 9150761
TI  - Micronucleus induction in germ and somatic cells of the mouse after exposure to
      the butadiene metabolites diepoxybutane and epoxybutene.
AB  - The genotoxicity of diepoxibutane (DEB) and epoxybutene (EB), two of the main
      metabolites of 1,3-butadiene, was tested in the germ and somatic cells of the
      mouse by applying an MN assay in early spermatids, and in peripheral blood
      reticulocytes of a subgroup of the same animals. DEB (0.17 and 0.35 mmol/kg) and
      EB (0.35, 0.70 and 1.04 mmol/kg) were administered i.p. In the germ cell assay,
      significant increases of MN were observed after treatment of premeiotic S-phase
      cells with both butadiene metabolites, but DEB was shown to be more powerful than
      EB in the induction of chromosomal damage. A weak effect of the same compounds
      was also found after treatment of late spermatocytes, approaching the meiotic
      divisions. From the MN assay in peripheral blood reticulocytes, a statistically
      significant increase of the frequency of MN was detected at each dose tested for
      both chemicals. However, the results have again shown that DEB is much more
      efficient than EB in inducing chromosome damage.

PMID- 9150762
TI  - The effect of dietary flavonoids on DNA damage (strand breaks and oxidised
      pyrimdines) and growth in human cells.
AB  - The effects of the flavonoids quercetin, myricetin and silymarin on DNA damage
      and cytotoxicity in human cells were investigated. DNA strand breaks and oxidised
      pyrimidines were determined using alkaline single cell gel electrophoresis (the
      comet assay). Inhibition of cell growth was also measured. Caco-2 (colon), HepG2
      (liver), HeLa (epithelial) cells and normal human lymphocytes showed different,
      dose-dependent susceptibilities (in terms of strand breakage) to the various
      flavonoids, quercetin being the most damaging. This agreed well with the ability
      of the flavonoids to inhibit cell growth. None of the flavonoids induced DNA base
      oxidation above background levels. All of the flavonoids under investigation
      caused depletion of reduced glutathione, which, in the case of quercetin,
      occurred prior to cell death. Neither cytotoxicity nor genotoxicity was
      associated with the antioxidant enzyme capacity (glutathione, glutathione
      reductase, glutathione peroxidase and catalase) of the cells.

PMID- 9150763
TI  - SCE analysis in peripheral blood lymphocytes of a group of filling station
      attendants.
AB  - Petroleum derivatives constitute a complex mixture of chemicals which contain
      known genotoxicants. Thus, chronic occupational exposure to such derivatives may
      be considered to possess genotoxic risk. Service station attendants are workers
      exposed to petroleum derivatives and, as consequence, biomonitoring studies
      designed to evaluate the genetic risk are required. Here we present the data on
      sister chromatid exchange (SCE) frequencies, proliferation rate index (PRI) and
      cells with high frequency of SCE (HFC) from a group of 42 attendant workers. In
      addition, data from a group of 45 unexposed (controls) are presented. The results
      obtained indicate that there are no significant differences in SCE values between
      the exposed workers when compared to the non-exposed individuals. The only
      difference is found when smoking habit is considered, the smokers having
      significant increases in the SCE frequency. There is a slight increase in the HFC
      frequency of the occupationally exposed group but the difference did not attain
      statistical significance.

PMID- 9150764
TI  - Genotoxic effects of 2-trans-hexenal in human buccal mucosa cells in vivo.
AB  - In 7 non-smoking healthy volunteers, the number of micronuclei (MN) was
      determined in exfoliated buccal mucosa cells before and after rinsing the mouth
      with an aqueous 10 ppm solution of 2-trans-hexenal during 3 consecutive days. All
      individuals showed at least a doubling of the MN frequency during one of the next
      4 days. An increase of the mean group MN frequency was observed on the fourth
      day, becoming significant between the sixth and the seventh day. During the next
      2 days, the MN frequency dropped down to nearly the control level. In a second
      study, 7 other volunteers were examined before and after eating 3-6 bananas per
      day over a period of 3 days. The bananas contained about 35 ppm of hexenal. Six
      of the 7 individuals showed at least a doubling of the MN frequency during one of
      the next 6 days. An increase in the mean MN counts was also observed, but the
      difference to the control value become non-significant during the test period.
      The results show for the first time that the flavoring constituent 2-trans
      hexenal, which is present in many human foods exerts genotoxic effects on human
      buccal mucosa cells in vivo.

PMID- 9150765
TI  - Species-specificity of pyrimethamine in the rodent bone marrow micronucleus test.
AB  - An antiprotozoal agent pyrimethamine is a potent clastogen that induces
      structural chromosome aberrations and micronuclei in cultured Chinese hamster
      (CHL) cells in vitro. Our previous study on the compound, however, demonstrated
      no significant induction of micronuclei in the mouse bone marrow micronucleus
      test, even with dosings on 4 consecutive days. In the present study, we
      investigated the clastogenicity of pyrimethamine in the rat bone marrow
      micronucleus test. An obvious dose-dependent increase in the frequency of
      micronucleated polychromatic erythrocytes (MNPCEs) was observed when the compound
      was given 3 times by oral gavage at 20-120 mg/kg/day. The MNPCE frequency at the
      highest dose was 80 times that of the control group. Single dose of pyrimethamine
      at 80 and 160 mg/kg also significantly induced MNPCEs. Thus, pyrimethamine showed
      species-specific effects in rodent bone marrow micronucleus assays. Our finding
      implies that micronucleus tests using not only mouse, but also rat, may be
      necessary for the evaluation of clastogens detected in in vitro cytogenetic
      studies.

PMID- 9150766
TI  - DNA damage induced by 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX)
      in HL-60 cells and purified DNA in vitro.
AB  - Chlorinated tap water often contains 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]
      furanone (MX), which is a potent directly acting bacterial mutagen. We have
      investigated the induction of DNA damage by MX in a promyelocytic human leukaemia
      cell line (HL-60 cells). Exposure of HL-60 cells to 100-300 microM MX resulted in
      increased levels of DNA single-strand breaks and/or alkali-labile sites (SSBs) as
      detected by alkaline filter elution. When adding inhibitors of DNA break repair
      (AraC plus hydroxyurea), increased levels of DNA SSBs were observed at very low
      concentrations (1-3 microM) of MX, as observed by both alkaline filter elution
      and the single-cell gel electrophoresis assay. Increased DNA SSBs could also be
      observed if DNA repair inhibitors were added immediately after exposure to 10
      microM MX, indicating that low concentrations of MX cause a relatively stable
      modification of DNA that may be recognized and incised by DNA repair enzyme
      activities. Further studies with DNA break repair inhibitors indicated that HL-60
      cells exposed to 10 microM MX for 1 h repaired 50% of their initial DNA damage
      during a 2-h period and the repair appeared to be complete at 22 h. Analysis of
      MX-treated DNA by sequencing methods indicated that MX preferentially reacts with
      guanines in DNA.

PMID- 9150767
TI  - A comparative investigation of DNA adducts, DNA strand breaks and gene mutations
      induced by benzo[a]pyrene and (+/-)-anti-benzo[a]pyrene-7,8-diol 9,10-oxide in
      cultured human cells.
AB  - Genotoxic effects of benzo[a]pyrene (BP) and its reactive metabolites (+/-)-anti
      benzo[a]pyrene-7,8-diol 9,10-oxide ((+/-)-anti-BPDE) were comparatively
      investigated in vitro with the permanent human fibroblast cell line MRC5CV1.
      Induced DNA adducts were measured by 32P-postlabeling, DNA strand breakage was
      determined by the comet assay and the HPRT gene mutation test was used to detect
      cytotoxicity and mutagenicity. Treatment of MRC5CV1 cells with S9 mix-activated
      BP or with (+/-)-anti-BPDE resulted in a concentration-dependent increase in DNA
      adducts and strand breaks. Genotoxic effects of BP and (+/-)-anti-BPDE were
      detected by 32P-postlabeling and the comet assay with similar sensitivity.
      However, under the same experimental conditions, a clear induction of gene
      mutations was only found after (+/-)-anti-BPDE treatment. The relationship
      between the induction of primary DNA alterations like DNA strand breaks and DNA
      adducts and the induction of gene mutations is discussed.

PMID- 9150768
TI  - Induction of unique tandem-base change mutations in bacterial spores exposed to
      extreme dryness.
AB  - Despite the remarkable resistance to desiccation, Bacillus subtilis spores
      manifest indications of DNA damage when being kept in an extremely dry
      environment made by high vacuum. Spores of strain TKJ3422 (uvrA10 spl-1 recA4)
      with triple repair defects lost colony-forming capacity dependent on the duration
      and strength of the exposure. Mutations to rifampicin resistance were induced in
      the spores of the strain HA101 with wild-type repair capability and the strain
      TKJ6312 (uvrA10 spl-1) with double repair defects. The majority of nalidixic acid
      resistant mutations induced by the exposure to high vacuum belonged to one
      particular allele gyrA12 carrying a tandem-base change, 5'-CA to 5'-TT, at codon
      84 of the gyrA gene coding for DNA gyrase subunit A. This allele has never been
      found among more than 500 mutants obtained by various treatments other than
      vacuum exposure. These results indicate forced dehydration of DNA in the
      microenvironment of the spore core causes unique damage leading to lethal and
      mutagenic consequences.

PMID- 9150769
TI  - Neurological complications of subarachnoid and epidural anaesthesia.

PMID- 9150770
TI  - Severe complications associated with epidural and spinal anaesthesias in Finland
      1987-1993. A study based on patient insurance claims [see comment].
AB  - BACKGROUND: The Patient Injury Act has been in effect in Finland since 1 May
      1987. This legislation is a no-fault compensation scheme and implies that if a
      patient during the course of medical treatment suffers any injury as a result of
      that treatment he or she may file a claim to the Patient Insurance Association
      (PIA). From 1 May 1987 to 31 December 1993, 23,500 claims for compensation were
      made. METHODS: All claims made to PIA involving spinal and epidural anaesthesias
      during the above period were collected and reviewed and a data base was prepared.
      The total number of anaesthetics given during this period was estimated by
      sending questionnaires to every hospital in the country. RESULTS: Eighty-six
      claims were associated with spinal and/or epidural anaesthesia. Respectively, the
      total the number of spinal and epidural anaesthesias administered was 550,000 and
      170,000. There were 25 serious complications associated with spinal anaesthesia:
      cardiac arrests (2), paraplegia (5), permanent cauda equina syndrome (1),
      peroneal nerve paresis (6), neurological deficits (7), and bacterial infections
      (4). The 9 serious complications which were associated with epidural anaesthesia
      were: paraparesis (1), permanent cauda equina syndrome (1), peroneal nerve
      paresis (1), neurological deficit (1), bacterial infections (2), acute toxic
      reactions related to the anaesthetic solution (2), and overdose of epidural
      opioid (1). CONCLUSIONS: According to this material the incidence of serious
      complications was 0.45:10,000 following spinal and 0.52:10,000 following epidural
      anaesthesia. Atraumatic technique, careful patient selection and early diagnosis
      and treatment of complications are essential in avoiding permanent injury.

PMID- 9150771
TI  - Peripheral neurologic deficits in relation to subarachnoid or epidural
      administration of local anesthetics for surgery. A survey of 21 cases.
AB  - BACKGROUND: Recent case reports have suggested that subarachnoid or epidural
      administration of local anesthetics may cause peripheral neurologic deficits.
      METHODS: To describe the course and evaluate possible risk factors of such
      reactions, 21 reports in the Swedish adverse drug reactions register were
      reviewed. RESULTS: The reports concerned subarachnoid administration of
      hyperbaric lidocaine (n = 9), plain bupivacaine (n = 4), hyperbaric bupivacaine
      (n = 2), bupivacaine with epinephrine (n = 1) and mepivacaine (n = 1), and
      epidural administration of bupivacaine (n = 2) and mepivacaine (n = 2). Pain in
      the lower extremities was reported in 12 patients (57%) and
      paresthesias/hypesthesias were reported in 11 patients (52%). Seven reports (33%)
      concerned low back pain or abdominal pain from Th9-Th10 and downwards. Urinary
      incontinence was reported in 3 patients, fecal incontinence in 2 patients, and
      erectile dysfunction, loss of sensation of full bladder and quadriceps muscle
      paresis were each reported in one patient. Two clinically distinct subgroups of
      patients were identified, one group with reversible nerve root affection which
      disappeared within 2 weeks and one group with apparently irreversible nerve root
      affection, still persistent after 1 month to 4 years. In the group with
      reversible root symptoms, none had motor deficits, whereas 50% had motor deficits
      in the group with irreversible symptoms. Possible risk factors include
      concomitant peripheral neurologic disease and use of other drugs associated with
      neurotoxicity. CONCLUSIONS: This database study does not contain complete
      information for the cases reported, and a causal relationship between
      subarachnoid or epidural administration of local anesthetics and neurologic
      deficits therefore remains uncertain. The increase in the number of reports on
      lidocaine after the introduction of very fine-bore spinal needles is consistent
      with the suspicion that lidocaine at the concentration 50 mg/ml is neurotoxic and
      that it may not be diluted rapidly enough in the cerebrospinal fluid when
      injected through such needles.

PMID- 9150772
TI  - Comparison of continuous epidural infusion of fentanyl and bupivacaine with
      intermittent epidural administration of morphine for postoperative pain
      management in children.
AB  - BACKGROUND: The aim of this study was to compare epidural infusion of bupivacaine
      and fentanyl and intermittent epidural morphine with regard to analgesic effect,
      and incidence and severity of side effects in children undergoing major abdominal
      or genito-urological surgery in order to improve the postoperative pain
      management of children. METHODS: A double-blind, block-randomised study design
      was used. Thirty-one children aged 3 months to 6 years undergoing major abdominal
      or genito-urological surgery were studied. After induction of anaesthesia a
      lumbar epidural catheter was placed at L3-4 or L4-5. Postoperatively, the
      children received either 30 micrograms/kg of morphine every 8 h or a continuous
      infusion of fentanyl 2 micrograms/ml and bupivacaine 1.0 mg/ml at a rate of 0.25
      ml.kg-1.h-1. All children additionally received rectal paracetamol in doses of 50
      100 mg.kg-1.d-1 on a regular basis, and amol in doses of 50-100 mg.kg-1.d-1 on a
      regular basis, and if necessary supplementary intravenous morphine in doses of 50
      micrograms/kg. Postoperatively, pain, administration of supplemental morphine and
      side effects were recorded 5 times by one observer during the day of surgery and
      the first postoperative day. All children had an epidural catheter throughout the
      study period. RESULTS: Both regimens provided effective analgesia, but
      significantly better pain relief was obtained in children receiving the
      fentanyl/bupivacaine regimen. Sedation, pruritus, vomiting, and administration of
      antiemetics were seen in both treatment groups, and even though both the
      incidence and severity of side effects tended to be higher in children receiving
      morphine, no statistically significant difference was found. No episodes of
      respiratory depression or motor blockade were noticed. CONCLUSIONS: Continuous
      epidural infusion of fentanyl and bupivacaine was found to be superior to
      intermittent epidural morphine. The initial regimen should be fentanyl 2
      micrograms/ml and bupivacaine 1.0 mg/ml infused at a rate of 0.25 ml.kg-1.h-1.

PMID- 9150773
TI  - Preoperative infiltration of bupivacaine--effects on pain relief and trauma
      response (cortisol and interleukin-6).
AB  - HYPOTHESIS: Subcutaneous infiltration of bupivacaine before skin incision can
      reduce postoperative pain and modulate the stress response. METHODS: In a
      randomized study on pain relief after hysterectomy 29 patients were referred into
      one of three groups, receiving 30 ml of bupivacaine 0.25% with adrenaline, 30 ml
      of saline or no infiltration along the line of the proposed incision 10 min
      before start of surgery. A Visual Analogue Scale was used for repeated pain
      ratings. Postoperative pain relief was provided with patient-controlled analgesia
      with intravenous morphine 0.04 mg/kg. Lockout time was 10 min. The immunological
      and endocrine stress response to trauma was reflected by blood interleukin-6 (IL
      6) and cortisol concentrations measured during 72 h following skin incision.
      RESULTS: There were large individual variations in the accumulated postoperative
      consumption of morphine at 20 h after start of surgery. It was significantly
      reduced in patients receiving infiltration of bupivacaine. They used 39 mg (9-62)
      median (range) of intravenous morphine whereas the patients in the saline group
      used 65 mg (47-120) and patients in the control group used 54 mg (36-130) (P <
      0.05). Significant elevation of plasma IL-6 and serum cortisol levels appeared in
      all groups with peak values at 3 h. There were no differences between the groups.
      There was a correlation between cortisol and IL-6. Six of the 29 patients had a
      postoperative infection which was reflected in increased IL-6 levels. CONCLUSION:
      Preoperative subcutaneous infiltration of bupivacaine significantly reduced the
      postoperative consumption of intravenous morphine.

PMID- 9150774
TI  - Antinociceptive effect of perioperative adenosine infusion in abdominal
      hysterectomy.
AB  - BACKGROUND: Adenosine (ADO), and stable analogs thereof, have been shown to exert
      antinociceptive action in cutaneous and deep somatic pain under experimental and
      clinical conditions in animals and in humans. The aims of this randomized double
      blind placebo-controlled study were to evaluate if a low dose of intravenous
      (i.v.) ADO could reduce the requirements of volatile anesthetic and postoperative
      opioid in connection to hysterectomy, where visceral nociception significantly
      contributes to pain. METHODS: Forty-three women, age 32-65 years, ASA I and II,
      scheduled for abdominal hysterectomy, were assigned to receive an i.v. infusion
      of either adenosine, 80 micrograms.kg-1.min-1, or placebo during surgery.
      Anesthesia was maintained with isoflurane (ISO)/N2O/ O2 inhalation.
      Postoperatively, a reduced dose of 40 micrograms.kg-1.min-1 was continued for 3
      h. RESULTS: The end-tidal (ET-) ISO was equal between groups before surgery.
      During surgery, the ISO requirement was increased, compared to the preoperative
      level, in the placebo group, while the requirement declined in the ADO group. The
      overall ISO requirement in the ADO group was reduced by 36% (P < 0.002). The
      first 24 h postoperative opioid requirement, with equal resting pain in both
      groups, was 18% (P < 0.05) lower in the ADO group. CONCLUSION: A low dose of
      perioperative adenosine infusion in abdominal hysterectomy reduces the
      requirements of volatile anesthetic and postoperative opioid analgesic.

PMID- 9150775
TI  - Analysis of anaesthesia in patients suspected to be susceptible to malignant
      hyperthermia before diagnostic in vitro contracture test.
AB  - BACKGROUND: It is well known that patients susceptible to malignant hyperthermia
      (MH) do not always develop clinical signs of MH at their first anaesthetic. Large
      material concerning this epidemiological problem do not exist. Therefore, we
      undertook the present investigation at the Danish Malignant Hyperthermia
      Register. METHODS: Retrospective analysis of anaesthetics given to 371 patients
      before in vitro contracture test (IVCT) for susceptibility to MH or before death
      of MH. Patients (or relatives in the case of a dead patient) gave information
      about previous anaesthetics and anaesthetic charts were collected and reviewed.
      RESULTS: Fifteen patients died of clinical MH, 112 patients survived an episode
      of suspected MH, and 244 patients were relatives of the above. Of the 127
      patients with clinical signs of MH, 37% had received anaesthesia before, and
      trigger agents (potent inhalational agents and/or suxamethonium) were used in 98%
      of patients with no statistical difference between MH-susceptible (MHS) and non
      susceptible (MHN) patients. Emergency anaesthesia was more frequent in patients
      with fulminant MH compared to those with abortive forms of MH (P < 0.01). Of the
      244 relatives, 48% had received anaesthesia before MH was suspected in the family
      and trigger agents were used in 44% of the anaesthetics without statistical
      difference between MHS and MHN relatives. In 17 cases, trigger agents were used
      for anaesthesia after MH was suspected in the family, but before IVCT.
      CONCLUSION: The clinical expressivity of the MHS phenotype was found to be 34%
      54%.

PMID- 9150776
TI  - Haemodynamics during inhalation of a 50% nitrous-oxide-in-oxygen mixture with and
      without hypovolaemia.
AB  - BACKGROUND: Inhalation of a gas mixture containing 50% nitrous oxide in oxygen
      (N2O/O2) is widely used for pain relief in emergency situations, which may also
      be associated with blood loss. The aim of this study was to evaluate the
      haemodynamic effects of this gas mixture in normo- and hypovolaemic subjects.
      METHODS: Six healthy males were studied during inhalation of N2O/O2 before and
      after withdrawal of 900 ml of blood. On each occasion, we measured systemic and
      pulmonary arterial pressures, cardiac output, blood gases, extravascular lung
      water, and the blood flow and oxygen consumption in the whole body, liver and
      kidneys. RESULTS: Inhalation of N2O/O2 reduced the stroke volume and increased
      peripheral resistance. Oxygen uptake decreased in the liver (-30%) and in the
      whole body (-23%). Blood withdrawal reduced the pulmonary arterial and central
      venous pressures (-30 to -50%) and further decreased stroke volume and the blood
      flows to the liver and the kidney (-15%). The extravascular lung water tended to
      increase both during inhalation of N2O/O2 and during hypovolaemia. CONCLUSION:
      N2O/O2 aggravated the hypokinetic circulation induced by hypovolaemia. However,
      the oxygen consumption decreased only during inhalation of N2O/O2. This opens up
      the possibility that the cardiodepression associated with N2O/O2 is caused by a
      change in metabolic demands.

PMID- 9150777
TI  - Can final EMG baseline be used as a reference to calculate neuromuscular
      recovery?
AB  - BACKGROUND: Investigations recording recovery times of muscle relaxants have used
      initial or final baseline of a neuromuscular trace, or both, as a reference for
      data analysis. We evaluated the use of final baseline of EMG traces as a reliable
      reference to calculate recovery times. METHODS: We analyzed EMG traces from 82
      children who had full spontaneous neuromuscular recovery following a single dose
      of mivacurium. Times from administration of mivacurium to 25, 50, 75, and 90% EMG
      recoveries were measured using both initial and final baselines as a reference.
      EMG traces with final baseline of 100 +/- 10% of the initial baseline were
      regarded as optimal. Recovery times from all other traces were compared to the
      times obtained from these optimal traces. Poor final baseline was defined as that
      of < 80% of initial baseline. Inter-group comparisons were made using Kruskal
      Wallis test followed by Mann-Whitney U tests. RESULTS: EMG recovery times were
      similar for optimal traces whether the reference was the initial or the final
      baseline of the EMG trace. If the final baseline was used as the reference, then
      traces with poor final EMG baseline also showed similar neuromuscular recovery
      times. If the initial baseline was used as the reference for EMG traces with poor
      final baseline, then neuromuscular recovery times became 24-55% longer (P <
      0.05). CONCLUSIONS: We conclude that the final baseline of an EMG trace can be
      used as a reference for calculations of neuromuscular recovery times following a
      bolus injection of mivacurium.

PMID- 9150778
TI  - Nitrous oxide has different effects on the EEG and somatosensory evoked
      potentials during isoflurane anaesthesia in patients.
AB  - BACKGROUND: Electroencephalogram (EEG) and somatosensory evoked potentials (SEPs)
      are altered by inhalation anaesthesia. Nitrous oxide is commonly used in
      combination with volatile anaesthetics. We have studied the effects of nitrous
      oxide on both EEG and SEPs simultaneously during isoflurane burst-suppression
      anaesthesia. METHODS: Twelve ASA I-II patients undergoing abdominal or
      orthopaedic surgery were anaesthetized with isoflurane by mask. After intubation
      and relaxation the isoflurane concentration was increased to a level at which an
      EEG burst-suppression pattern occurred (mean isoflurane end-tidal concentration
      1.9 (SD 0.2) %. With a stable isoflurane concentration, the patients received
      isoflurane-air-oxygen and isoflurane-nitrous oxide-oxygen (FiO2 0.4) in a
      randomized cross-over manner. EEG and SEPs were simultaneously recorded before,
      and after wash-out or wash-in periods for nitrous oxide. The proportion of EEG
      suppressions as well as SEP amplitudes for cortical N20 were calculated. RESULTS:
      The proportion of EEG suppressions decreased from 53.5% to 34% (P < 0.05) when
      air was replaced by nitrous oxide. At the same time, the cortical N20 amplitude
      was reduced by 69% (P < 0.01). CONCLUSION: The results suggest that during
      isoflurane anaesthesia, nitrous oxide has a different effect on EEG and cortical
      SEP at the same time. The effects of nitrous oxide may be mediated by cortical
      and subcortical generators.

PMID- 9150779
TI  - The haemodynamic effects of rocuronium and vecuronium are different under
      balanced anaesthesia.
AB  - BACKGROUND: Rocuronium has been reported to have minimal haemodynamic effects.
      However, this conclusion has been drawn primarily from investigations conducted
      under narcotic-based anaesthesia. This study was designed to evaluate the
      cardiovascular effects of rocuronium under isoflurane/N2O/fentanyl anaesthesia
      and to compare rocuronium's haemodynamic effects to those of vecuronium and
      pancuronium. METHODS: Anaesthesia was induced with fentanyl 2 micrograms/kg,
      thiopentone 4 mg/kg, and suxamethonium 0.5 mg/kg in 75 ASA I or II patients.
      After tracheal intubation, anaesthesia was maintained with isoflurane 0.5% and
      N2O 50% in oxygen. Five min after intubation (baseline), patients randomly
      received either vecuronium 100 micrograms/kg, rocuronium 600 micrograms/kg,
      rocuronium 900 micrograms/kg, rocuronium 1200 micrograms/kg, or pancuronium 140
      micrograms/kg. One min after administration of muscle relaxant, mean arterial
      pressure (MAP) and heart rate (HR) were recorded and were subsequently measured
      at 1-min intervals for the next 4 min. RESULTS: HR decreased significantly (P <
      0.05) at all times compared to baseline in patients receiving vecuronium. HR
      significantly (P < 0.05) increased in those receiving rocuronium 1200
      micrograms/kg or pancuronium. Patients who received vecuronium had a significant
      (P < 0.05) decrease in MAP at all times compared to baseline. Comparing results
      between groups, patients who received rocuronium or pancuronium had significantly
      (P < 0.05) higher MAP compared to those administered vecuronium. CONCLUSION: The
      haemodynamic effects of rocuronium and vecuronium are different under balanced
      anaesthesia. Rocuronium may attenuate the fall in MAP that often occurs under
      balanced anaesthesia without surgical stimulation.

PMID- 9150780
TI  - Tramadol in the treatment of postanesthetic shivering.
AB  - BACKGROUND: As an inhibitor of the reuptake of serotonin and norepinephrine in
      the spinal cord, the mechanism of action of tramadol resembles that of nefopam,
      which has been used in the treatment of postanesthetic shivering. METHODS: In a
      randomized, placebo-controlled, double-blind study, we assessed the effects of
      tramadol (0.5 mg.kg-1, 1 mg.kg-1 and 2 mg.kg-1 i.v.) or normal saline on
      shivering after a standardized general anesthesia in 40 adult patients, ASA
      physical status I or II (group 1), and in 64 adult patients regardless of the
      foregoing general anesthesia and ASA physical status (group 2). RESULTS: Tramadol
      1 mg.kg-1 or more abolished shivering completely 5 min after treatment in all
      patients of groups 1 and 2. In group 1, the three dosages of tramadol were not
      statistically different in lowering the severity and prevalence of postanesthetic
      shivering. Tramadol 0.5 mg.kg-1 was significantly slower than tramadol 1 or 2
      mg.kg-1 in tempering the severity as well as lowering the prevalence of
      postanesthetic shivering in group 2. CONCLUSION: Tramadol's distinct features in
      the treatment of shivering reside in its high safety profile and weak sedative
      properties, particularly in patients with poor cardiorespiratory reserve, in
      outpatients and on recurrence of shivering.

PMID- 9150781
TI  - Outcome effects of different protective hypothermia levels during cardiac arrest
      in rats.
AB  - BACKGROUND: Although hypothermia is widely used to protect the brain during
      cardiac and neurologic surgery, the optimal level of cooling has not been
      established. This study examined the protective effect of graded levels of
      surface cooling on cerebral function in rats after complete global cerebral
      ischemia. METHODS: Groups of ketamine-anesthetized rats (13 animals in each
      group) were cooled to cranial temperatures of 34, 30, 27, 24, or 22 degrees C
      before circulatory arrest. Also a normothermic (37 degrees C) group was tested.
      After cooling, an 11-min circulatory arrest was produced by atraumatic chest
      compression. Circulatory arrest was followed by cardiopulmonary resuscitation and
      rewarming without postischemic intensive care. On the fifth postinsult day,
      neurologic outcome was scored on a 50-point neurodeficit scale (NDS 0 = normal).
      The percent of ischemic pyramidal neurons in the CA1 hippocampal region was also
      determined. RESULTS: There were no survivors in the normothermic group.
      Neurologic recovery was enhanced with 30 degrees C cranial temperature, as
      compared to outcome in the 34 degrees C group. Further cooling did not change
      outcome. The neurodeficit scales were significantly lower in all other groups
      compared to the 34 degrees C group on the fifth postinsult day. The percent of
      ischemic neurons did not change significantly as a function of cooling, but the
      lowest count appeared at 27 degrees C. CONCLUSION: In this model, moderate (30
      degrees C) cooling improved neurologic outcome. There was no additional benefit
      from more extreme hypothermia.

PMID- 9150782
TI  - Magnesium--a profibrillatory or antifibrillatory drug depending on plasma
      concentration, heart rate and myocardial perfusion.
AB  - BACKGROUND: The opinions on the efficacy of magnesium as an antiarrhythmic drug
      vary considerably. The action of magnesium on vulnerability to fibrillation was
      therefore investigated in anaesthetized, open-chest pigs under different
      conditions as regards plasma concentration, heart rate and myocardial perfusion.
      METHODS: Vulnerability to fibrillation was assessed by electrical fibrillation
      threshold (EFT), measured with 100-ms duration diastolic impulses. These stimuli
      were delivered to the heart normally perfused, at a usual (90 and 120 beats/min)
      or accelerated (180 beats/min) rate. Vulnerability to fibrillation was also
      assessed at the high rate (180 beats/min) in the heart made ischaemic by complete
      occlusion of the left anterior descending coronary artery near its origin. EFT
      was then measured at the end of occlusion periods which were of increasing
      duration (30, 60, 90, 120 s). Monophasic action potential (MAP) duration,
      intraventricular conduction time, left ventricular dP/dt max (LVdP/dt max) and
      mean blood pressure were concurrently measured. RESULTS: In the absence of
      ischaemia, 5 mumol.kg-1.min-1 magnesium i.v. infusion, which raised plasma
      concentration to 1.78 +/- 0.14 mmol/L, lowered EFT, measured at the rate of 116
      beats/min, from 14.0 +/- 1.1 to 6.8 +/- 1.0 mA (P < 0.001), without significant
      variation of the other parameters. Administered as previously or in a markedly
      higher dose (400 mumol.kg-1 loading dose and 10 mumol.kg-1.min-1 infusion) which
      raised plasma concentration up to 4.84 +/- 0.52 mmol/L, magnesium significantly
      influenced neither EFT nor MAP duration, reduced by the high rate (180 beats/min)
      to 6.2-6.7 mA and 212-220 ms respectively. Under the same conditions, at the same
      180 beats/min rate, ischaemia brings about a fall of EFT, from 6.9 down to nearly
      0 mA, with occurrence of fibrillation, in approximately 120 s. Magnesium failed
      to slow this fall and to delay the onset of fibrillation. In contrast, within the
      minutes following the end of occlusion, magnesium increased EFT to a great extent
      (from 7.1 +/- 0.4 to 13.5 +/- 0.7 mA, P < 0.001), with a significant prolongation
      of MAP duration (212 +/- 6 to 234 +/- 8 ms, P < 0.01). CONCLUSION: Magnesium may
      develop profibrillatory or antifibrillatory effects depending on plasma
      concentration, heart rate and myocardial perfusion.

PMID- 9150783
TI  - Inhibitory effect of local anaesthetics on reactive oxygen species production by
      human neutrophils.
AB  - BACKGROUND: Reactive oxygen species (ROS) generated from neutrophils accumulated
      in various major organs are thought to play a pivotal role in the pathogenesis of
      host auto-injury. Lidocaine has been shown to reduce the injury. We investigated
      the effect of local anaesthetics (lidocaine, mepivacaine and bupivacaine) on ROS
      production by neutrophils using an in vitro system. METHODS: We measured the
      production of superoxide (ferricytochrome c method), hydrogen peroxide (H2O2:
      scopoletin fluorescence technique), and hydroxyl radical (OH.: ethylene gas
      method) by neutrophils isolated from human adult volunteers in the absence and
      presence of lidocaine (2-200 micrograms/mL), mepivacaine (3-300 micrograms/mL),
      and bupivacaine (3-300 micrograms/mL). We also measured the ROS generation in a
      cell-free (xanthine-xanthine oxidase) system. RESULTS: Lidocaine and mepivacaine
      at higher levels significantly decreased the production of ROS by neutrophils.
      However, these local anaesthetics at clinically relevant blood concentrations had
      no effect on the levels of ROS. Furthermore, lidocaine and mepivacaine failed to
      reduce ROS generated by the cell-free system. Bupivacaine did not decrease ROS
      generation by either generating system. CONCLUSION: In conclusion, in the present
      in vitro system, only concentrations of lidocaine and mepivacaine 100-fold higher
      than clinically feasible ones reduced ROS production by human neutrophils.
      However, the local anaesthetics at clinically relevant blood concentrations had
      no suppressive effect. Further studies using in vivo systems are required to
      elucidate the inhibitory effects of local anaesthetics on ROS generation in
      clinical settings.

PMID- 9150784
TI  - A tube in the pharynx for emergency ventilation.
AB  - BACKGROUND: If the endotracheal placement of a nasal advanced tube fails,
      ventilation via this tube could bridge the time until a fibreoptic bronchoscope
      is available. This study investigates the efficiency of ventilation via a tube
      resting with its tip in the pharynx near the glottis. METHODS: In 20 patients
      respiratory data during ventilation via a pharyngeally placed tube were recorded
      by means of pulse oximetry, capnometry and side-stream spirometry. Results were
      compared with those measured previously in the same patients during conventional
      facemask ventilation. RESULTS: Oxygen saturation and end-tidal carbon dioxide
      concentration remained unchanged using ventilation via facemask (SO2 98.5 +/-
      0.9%, FECO2 4.5 +/- 0.7 vol%) or pharyngeal tube (SO2 98.6 +/- 0.7%, FECO2 4.8 +/
      0.4 vol%). No significant differences were found between the two groups with
      regard to peak airway pressure, tidal volume leakage, compliance and resistance
      of the respiratory system. CONCLUSIONS: Our results suggest an effective
      ventilation and oxygenation via a tube placed with its tip in the pharynx. This
      technique may be helpful during difficult and prolonged nasal intubation.

PMID- 9150785
TI  - Blockade of ATP-sensitive K+ channel abolishes the anti-ischemic effects of
      isoflurane in dog hearts.
AB  - BACKGROUND: Although isoflurane is reported to have a protective effect against
      ischemic damage on the myocardium, the mechanisms of this effect are not clear.
      Activation of adenosine triphosphate sensitive potassium (KATP) channels is
      indicated to protect myocardium during ischemia. Thus, it was hypothesized that
      if isoflurane could activate KATP channels, blockade of KATP channels would
      decrease its cardioprotective effect. METHODS: Mongrel dogs, anesthetized with
      morphine, urethane, and chloralose, were subjected to 15 min of left anterior
      descending coronary artery occlusion followed by 60 min reperfusion. The dogs
      were divided into three groups: the control group (n = 8), ISO group (n = 8) and
      ISOGC group (n = 8). In the ISO and ISOGC groups, 1 MAC of isoflurane was
      administrated during ischemia and reperfusion. In the ISOGC group, 0.3 mg/kg of
      glibenclamide, the KATP channel blocker, was given 45 min before ischemia. Full
      thickness samples of myocardium were obtained and the concentrations of adenosine
      monophosphate, adenosine diphosphate, adenosine triphosphate (ATP), creatine
      phosphate and lactate in the endocardial portion of the myocardium were measured.
      RESULTS: The ischemia-reperfusion caused a 25.4% and 27.6% reduction of
      myocardial ATP in the control and ISOGC groups, respectively. In contrast, the
      ISO group showed only 11.0% reduction of ATP, which was significantly lower
      compared to the other groups (P < 0.01). CONCLUSIONS: Our results shows that
      blockade of the KATP channel abolishes cardioprotective effects of isoflurane in
      myocardial ischemia-reperfusion. The KATP channel may play a role in the ATP
      sparing effect of isoflurane.

PMID- 9150786
TI  - The use of indomethacin to treat acute rises of intracranial pressure and improve
      global cerebral perfusion in a child with head trauma.
AB  - BACKGROUND: The use of vasoconstrictors (e.g. dihydroergotamine, indomethacin)
      for the treatment of increased intracranial pressure (ICP) secondary to brain
      trauma is controversial. In particular, it has been suggested that
      vasoconstrictors be employed only for intracranial hypertension secondary to
      hyperemia, when venous jugular bulb saturation (SjO2) is > 75%. METHOD: We
      administered indomethacin as a bolus i.v. (5-10 mg) on 18 occasions to a multiple
      injured 3-year-old child with acute rises of ICP secondary to severe brain trauma
      (GCS score 7) determining a large hypodensity area in and swelling of the right
      hemisphere. RESULTS: Before indomethacin administration the average of mean ICP
      was 68.1 +/- 10.8 (SD) mm Hg (range 47-84) and the cerebral perfusion pressure
      (CCP) was 38.4 +/- 10.4 mm Hg (range 30-65). In response to indomethacin, ICP
      dropped in a few seconds to 22.7 +/- 5.6 and CCP increased to 82.4 +/- 6.1 mm Hg
      (P < 0.001), while the mean arterial pressure remained unchanged. On 6 occasions
      SjO2 was also evaluated immediately before and 5 and 10 min after indomethacin
      administration. Before indomethacin administration, SjO2 values were within the
      normal range on 2 occasions and abnormally low on four. SjO2 increased from the
      mean value of 45.6 +/- 15.7 to 59.8 +/- 8.9 (after 5 min) and 60.6 +/- 12.4%
      (after 10 min) (P < 0.01 versus pre-indomethacin). At the same time the cerebral
      venous pH increased from 7.43 +/- 0.01 to 7.45 +/- 0.01 (P = 0.01). These
      findinge suggest that the global cerebral perfusion was improved. Eighteen days
      after injury the child was awake and was discharged from the ICU. CONCLUSION: To
      our knowledge, increase of SjO2 in response to indomethacin has not been
      previously reported. Although great caution is necessary in the use of
      indomethacin for the treatment of ICP, these findings suggest that indomethacin
      can be useful for the treatment of acute rises of ICP compromising severely the
      CCP, even if SjO2 is normal or abnormally low. Under these circumstances,
      indomethacin can improve the global cerebral perfusion.

PMID- 9150787
TI  - Long QT interval syndrome with increased QT dispersion.
AB  - This case report describes the anaesthetic management of a patient with sporadic
      type long QT interval syndrome (LQTS), and increased QT dispersion, who presented
      for removal of an ovarian cyst. Beta adrenergic blockade and adequate depth of
      anaesthesia for successful management is emphasized. The successful use of
      epidural administration of lignocaine and opioids in addition to general
      anaesthesia is described.

PMID- 9150788
TI  - Is glycine a safe irrigating fluid?

PMID- 9150789
TI  - Streptomycin/lignocaine local infiltration in the treatment of hypertrophic scar
      pain. A preliminary report.

PMID- 9150790
TI  - Microcirculation in skeletal muscle during hypoperfusion.

PMID- 9150791
TI  - Manganese and copper-zinc superoxide dismutases in the developing rat retina.
AB  - To determine whether superoxide dismutases (SODs) may be connected with cellular
      differentiation in the retina, we studied these enzymes by immunolocalization and
      immunochemical quantitative analysis in developing rat retinas. Four days after
      birth, manganese superoxide dismutase (Mn-SOD) and copper-zinc superoxide
      dismutase (CuZn-SOD) immunoreactivities were observed in the neural retina but
      not in immature neuroblasts. In 9-day-old rats, Mn-SOD immunoreactivity was
      located in the ganglion cell layer, inner plexiform layer, some cells of the
      inner nuclear layer, outer plexiform layer, and photoreceptor inner segments
      differentiated from immature neuroblasts. CuZn-SOD immunoreactivity was found in
      the same sites except the photoreceptor inner segments. The immunohistochemical
      staining in 9-day-old rat retinas was the same as in adult retinas. Our
      quantitative analysis showed increased SODs when retinal cell differentiation
      ceased. Our results suggest that the concentration of SODs in retinal neuroblasts
      is too low that immunoreactivity of SODs cannot be visualized. When the
      differentiation of retinal neuroblasts progresses, SODs appear to be increased in
      mature retinal cells to protect them from oxidative stress induced by light
      exposure when the eyes are open.

PMID- 9150792
TI  - Vasoactive intestinal polypeptide immunoreactive nerves in the gill arch of
      teleost fish, Carassius auratus L.
AB  - The localization of vasoactive intestinal polypeptide (VIP)-immunoreactive (ir)
      nerve cell bodies and fibers has been studied in the gill arches of goldfish
      (Carassius auratus, L.) using the peroxidase-antiperoxidase (PAP)
      immunohistochemical method. It was found that VIP-ir nerve cell bodies are
      localized in connective tissue on the oral side of the gill arch; these cells
      were present as single cells, in couples or as small clusters. Moreover, a dense
      network of VIP-ir fibers was observed beneath the lining epithelium of the raker
      cushion. The possible involvement of this peptide in mucus secretion in the gill
      arches of teleost is discussed.

PMID- 9150793
TI  - Immunocytochemical identification of immature rat peritoneal mast cells using a
      monoclonal antibody specific for rat mast cells.
AB  - The lack of immunological or morphological markers makes identification of
      immature mast cells difficult. In the present study we have used a rat mast cell
      specific monoclonal antibody (mAb AA4) to immunolabel mast cells during
      repopulation of the peritoneal cavity. Peritoneal cells were collected six days
      after injection of distilled water and examined by light and electron microscopy.
      mAb AA4 stained immature mast cells in various stages of maturation including a
      population of very immature mast cells that could not be identified using
      conventional staining methods. These cells had virtually no cytoplasmic granules
      and peripherally located lobated nuclei. Thus, immunolabeling with mAb AA4 has
      revealed a population of very immature mast cells not previously reported during
      repopulation of the peritoneal cavity.

PMID- 9150794
TI  - Flow cytometric analysis of band 3 protein of human erythrocytes.
AB  - Flow cytometry was used to quantify the transmembrane anion exchanger (band 3
      protein) of human erythrocytes by covalently bound eosin-5-maleimide. In vitro
      and in vivo vesiculated red blood cells were investigated. The fluorescence and
      light scatter signals of cells after heat induced vesiculation, in vivo ageing,
      and in patients with hereditary spherocytosis were decreased. These results
      reflect a deficiency of band 3 protein which is presumably caused by membrane
      surface area loss. It was possible to distinguish control erythrocytes,
      erythrocytes from patients with hereditary spherocytosis, and from other forms of
      haemolytic anaemias on the basis of their light scatter and fluorescence signals
      characteristics.

PMID- 9150795
TI  - Development of hydrogen peroxide (H2O2)-generating oxidases in chick organs with
      special reference to kidneys.
AB  - The developmental pattern of H2O2-producing oxidases (OX) was studied in chick
      kidneys (mesonephros, metanephros), intestine, liver, yolk sac and adrenal glands
      between embryonic days (ED) 5-20 as well as in chick organs after hatching.
      Sections from snap frozen tissue fixed in cold cacodylate-buffered 2%
      glutaraldehyde were processed by cerium-DAB-Co-H2O2 methods for benzylamine OX,
      diamine OX, histamine OX, alpha-hydroxyacid OX, D-amino acid OX (AAOX) and
      monoamine OX (MAOX). Prenatally, only activities of AAOX and MAOX could be
      demonstrated. AAOX appeared primarily in the proximal tubular cells of both types
      of kidneys. In the metanephros the enzyme was also detected in the thick
      ascending limbs of Henle's loops. The amount of reaction product in tubular cells
      increased with their maturation. MAOX activity was detected in immature
      enterocytes, in smooth muscle cells of large systemic arteries (on ED 5-6) as
      well as in proximal tubular cells of the mesonephros and adrenal gland. Later the
      enzyme appeared also in smooth muscle cells of the intestinal wall and in
      endothelial and smooth muscle cells of arterioles of the mesonephros. In the
      metanephros MAOX was detected at the same locations with a time delay because of
      a developmental shift of the kidney. Inhibition tests revealed that MAOX differs
      in epithelial cells from that in smooth muscle cells. Benzylamine OX, diamine OX
      and histamine OX were detected postnatally in smooth muscle cells of the arterial
      media and muscularis externa of the intestinal wall with low activities. It is
      concluded that MAOX and AAOX activities represent useful markers in the
      development of renal tubules. In addition, MAOX activity can be considered an
      indicator of maturation of components of the vascular wall.

PMID- 9150796
TI  - Differences in the localization of the postsynaptic nitric oxide synthase I and
      acetylcholinesterase suggest a heterogeneity of neuromuscular junctions in rat
      and mouse skeletal muscles.
AB  - Recently, nitric oxide synthase (NOS) I has been identified in skeletal muscle
      fibers, where the enzyme is found to be associated to the sarcolemma by the alpha
      1-syntrophin-dystrophin complex. It has, however, been proposed that a
      substantial proportion of NOS I at the neuromuscular junction (NMJ) is of
      neuronal origin. We have, therefore, investigated the distribution of NOS I in
      NMJ of normal rats and mice as well as mdx mice which lack dystrophin and,
      consequently, NOS I in the sarcolemma region by enzyme histochemical and
      immunohistochemical techniques. Sites of NOS I accumulation, evident at NMJ of
      healthy animals, were absent in mdx mice, indicating a predominantly, if not
      exclusively, postsynaptic localization of NOS I at NMJ. Moreover, simultaneous
      demonstration of acetylcholinesterase (AChE) activity revealed a heterogeneity of
      NMJ in rat and mouse skeletal muscles: type I showed only AChE activity and was
      found to predominate; type II was spatially separated from the AChE-positive NMJ,
      occurred less frequently and contained both AChE activity and NOS I. These data
      suggest that type II NMJ are provided with additional regulatory mechanisms, such
      as free radical signaling by the NOS I-derived NO which may exert modulatory
      effects on the choline acetyltransferase/ACh/AChE pathway. Furthermore, type II
      may represent those NMJ where recently glutamate-gated NMDA-type Ca2+ channels
      have been described, which in analogy to those in the nervous system may serve
      also in skeletal muscle fibers as NOS I activators.

PMID- 9150798
TI  - Signal transduction and phagosome biogenesis in human macrophages during
      phagocytosis of Mycobacterium bovis BCG.
AB  - Downstream signal transduction via heterotrimeric GTP-binding proteins to protein
      kinase C has been reported to be a central event in induction of rapid
      phagocytosis of extracellular particles by macrophages. However, the signalling
      pathway involved in mycobacterial uptake and phagosome biogenesis is poorly
      understood, and there is lack of information about in situ localization of PKC,
      cytoskeletal proteins, and G-proteins in mycobacterial vacuoles. Employing
      immunocytochemical methods, we provide evidence that alpha-subunits of
      stimulatory and inhibitory G-proteins and PKC beta as well as two major
      cytoskeletal components, microfilaments and microtubules, participate in uptake
      of Mycobacterium bovis BCG by human macrophages and co-localize in phagosomes.
      This implies that cellular signalling via G-proteins and PKC beta may occur not
      only at the level of the plasma membrane; rather, the alpha-subunit of G-proteins
      and PKC beta may be translocated to the effector proteins involved in phagosomal
      biogenesis. A similar pattern of accumulation of G-proteins, PKC, and both
      microfilamental and microtubular cytoskeleton around vacuoles containing
      internalized latex beads indicates their general role in phagocytosis.

PMID- 9150797
TI  - Epidermal growth factor binding sites in the mouse exocrine and endocrine
      pancreas shown by in vivo quantitative microautoradiography and confocal laser
      scanning microscopy.
AB  - Microautoradiography at 3, 6 and 15 min after intravenous injection of 125I-EGF
      was used to investigate the distribution of epidermal growth factor (EGF) binding
      sites in the pancreas of normal male mice. The autoradiographs were observed by
      confocal laser microscopy, which allows the quantification of silver grains. The
      results demonstrated that both endocrine and exocrine pancreatic cells exhibited
      substantial specific binding of 125I-EGF. The highest level of EGF binding was
      found in the duct cells of the exocrine pancreas followed by the acinar cells.
      The cells of the islets of Langerhans also showed substantial specific binding of
      125I-EGF though the binding level was lower than that of the exocrine pancreas.
      In the control experiments, mice were injected with 125I-EGF and various amounts
      of unlabeled EGF.

PMID- 9150799
TI  - Apoptotic and necrotic cell death following kindling induced seizures.
AB  - The study was designed to determine which type of cell death occurs following
      kindling induced seizures, and to determine which neurons die. For this purpose
      seizures were kindled from the entorhinal cortex. Following a range of 5-85 stage
      5 seizures, rats were sacrificed, and the tissue was prepared for analysis. The
      TUNEL and silver impregnation methods were used to identify apoptotic or necrotic
      cell death, respectively. These methods were subsequently combined with
      immunocytochemistry, to determine if diseased neurons expressed somatostatin or
      the NMDA receptor (NMDAR1). The tissue analysis demonstrated that following
      kindling induced seizures, 1) hippocampal and extrahippocampal neurons die, 2)
      some neurons die through apoptosis, others through necrosis, and 3) some of the
      diseased neurons express somatostatin, others the NMDAR1 and that both
      subpopulations of neurons are present at hippocampal and extrahippocampal sites.

PMID- 9150800
TI  - Histochemical study of lectin binding in the major salivary glands of adult
      fallow-deer (Dama dama L.).
AB  - The sugar residues in glycoconjugates present in the parotid and mandibular
      glands of the adult fallow-deer were detected and characterized by using a
      battery of eight different lectin-horseradish peroxidase conjugates. In some
      cases a treatment with sialidase preceded the lectin staining. Parotid secretory
      cells produced glycoconjugates with N-acetylgalactosamine, N-acetylglucosamine
      and mannose residues. Mucous acinar cells were the most reactive sites of the
      mandibular gland and contained conspicuous quantities of oligosaccharides with
      terminal sialic acid radicals. Galactosil-(beta 1-->3)N-acetylgalactosamine was
      the most abundant penultimate sugar linked to N-acetylneuraminic acid. Mandibular
      mucous cells also presented N-acetylglucosamine and sialylated components with
      the terminal dimer sialic acid-N-acetylgalactosamine. Demilunar cells contained
      glycoconjugates with fucose and mannose residues. The apical surface of duct
      cells was stained by all the lectins.

PMID- 9150801
TI  - Sulphated polyanions in cytoplasm and nuclei of epithelial cells of Branchiostoma
      demonstrated by the cationic dye Cupromeronic Blue.
AB  - The intracellular occurrence and distribution of sulphated polyanions,
      interpreted to represent mucins, were studied in secretory epithelial cells in
      the primitive chordates Branchiostoma lanceolatum and B. floridae at the electron
      microscopical level by using Cupromeronic Blue (CMB). CMB-precipitates were
      mainly found within two potential types of mucin vesicles (apical and basal) and
      Golgi cisterns. The mucin vesicles form a distinct population of secretory
      granules different from another nonmucin granule population. Within the epidermal
      cells the staining intensity of the Golgi cisterns with CMB increased from the
      cis to the trans compartment. The pharyngeal mucous cells showed staining only in
      the trans Golgi compartment. These findings indicate, that CMB can be used for
      intracellular localization of mucins and that sulphation of the mucins in the
      investigated cells may occur within different compartments of the Golgi complex.
      Apparently the mucin is secreted apically but only in the epidermis it forms a
      dense layer covering the apical microvilli. In the Branchiostoma epidermal cells
      a layer of specialized basal vesicles occurred, containing unusually large and
      branched CMB-precipitates which possibly serve mechanical functions. In the
      nuclei CMB-precipitates were regularly demonstrated in the euchromatin of the
      cell types studied.

PMID- 9150802
TI  - A note on the preparation of whole mount samples suitable for observation with
      the confocal laser scanning microscope.
AB  - The effects of fixatives and pretreatment on the immunofluorescence of whole
      mount specimens prepared for confocal laser scanning microscopy (CLSM) were
      examined. Intact villi were obtained from the proximal small intestine of mice
      fixed with 4% paraformaldehyde (4P) or 0.5% paraformaldehyde and 15% of saturated
      picric acid (PPa). Before immunostaining for laminin and tenascin, each specimen
      was pretreated with deoxycholate, while some 4P-fixed specimens received further
      pepsin pretreatment. Regardless of the fixatives employed, laminin and tenascin
      showed adequate immunofluorescence. Without pepsin pretreatment, the 4P-fixed
      specimens emitted conspicuous background fluorescence, and immunofluorescence was
      weak in the lamina propria. Pepsin pretreatment reduced the background
      fluorescence, but also diminished the immunofluorescence, especially that of
      tenascin. The PPa-fixed specimens displayed intense immunofluorescence of laminin
      and tenascin with very little background, even deeply within the lamina propria.
      When the PPa-fixed specimens were immunostained for vasoactive intestinal
      peptide, immunopositive nerve fibres were observed within the lamina propria.
      Ultrastructural investigation of the PPa-fixed specimens revealed that membranous
      structures in all cells were almost lost while tissue architecture was well
      preserved. These results indicate that PPa fixation and pretreatment with
      deoxycholate are suitable for preparing whole mount specimens for CLSM studies.

PMID- 9150803
TI  - Functional and ultrastructural studies on the burst of c-kit ligand containing
      secretory cytoplasmatic vesicles.
AB  - A fibroblast-like cell line (D064) was established from canine marrow long-term
      cultures. These cells start to differentiate into hematopoietic progenitor
      precursors under the influence of c-kit ligand, functioning in an autocrine and
      paracrine fashion. The message for c-kit ligand is transcribed in the fibroblast
      like cell line and the ligand for the tyrosine-kinase c-kit is expressed on the
      cell surface as well as secreted in its soluble form. With a monoclonal antibody
      directed against all isoforms of c-kit ligand, the expression of c-kit ligand was
      investigated functionally and topographically by electron microscopy.
      Ultrastructural analysis revealed c-kit ligand in electron dense vesicles which
      were transported to the cell surface and burst to release the soluble, non
      membrane bound isoform of c-kit ligand. A membrane bound isoform of c-kit ligand
      was also present on the cell membrane.

PMID- 9150804
TI  - Transient expression of the serotonin transporter in the developing mouse
      thalamocortical system.
AB  - The serotonin transporter was visualized in sections through the developing mouse
      thalamus by autoradiography of [3H]citalopram binding. In late gestation, a high
      density of transporter expression appeared in the ventrobasal thalamic complex
      and medial geniculate body. During the first postnatal week, binding in these
      areas decreased to low levels. A similar pattern of transient [3H]citalopram
      binding was observed in the somatosensory cortex, although the rise and decline
      of labeling occurred some days later. The density of the serotonergic innervation
      in the ventrobasal thalamic complex is known to be very low during the entire
      developmental period. Therefore, these data suggest that the serotonin
      transporter may be expressed transiently by thalamic neurons projecting to the
      cerebral cortex (as a "heterocarrier") which are capable of taking up serotonin
      in the somatosensory cortex. We propose that serotonin may act temporarily as a
      "false" transmitter in thalamocortical axons.

PMID- 9150805
TI  - Angiotensin-converting enzyme inhibition in cirrhotic patients--pharmacokinetics
      of ramipril.
AB  - In an open trial, the pharmacokinetics of the angiotensin converting enzyme
      inhibitor ramipril and its active metabolite ramiprilat were studied in 12
      patients with liver cirrhosis. After a single oral dose of 5 mg ramipril plasma
      levels of the parent compound reached peak concentrations of 48.6 +/- 39.8 ng/ml
      after 0.7 +/- 0.5 h and declined rapidly to 0.7 +/- 1.2 ng/ml after 8 h. Plasma
      levels of ramiprilat reached peak concentrations of 3.8 +/- 2.9 ng/ml after 3.0
      +/- 2.2 h, thereafter declined slowly and could be detected up to 240 h. The
      total recovery of ramipril and metabolites in urine within 96 h was on average
      46.0 +/- 10.9% of the administered dose. Major fractions were due to
      diketopiperazines and glucuronides of ramipril and ramiprilat. The overall ACE
      inhibition was still 92.0 +/- 8.6%. In conclusion, patients with liver cirrhosis
      had enough capacity to metabolize and excrete the parent compound ramipril, but
      had not enough capacity to form ramiprilat, although enough ramiprilat was formed
      for sufficient ACE inhibition of about 90%. This indicates that titration of the
      dose should start with 5 mg or even lower doses in patients with markedly
      impaired liver function.

PMID- 9150806
TI  - Increased serum levels of soluble CD44-isoform v5 in rheumatic diseases are
      restricted to seropositive rheumatoid arthritis.
AB  - Serum levels of sCD44v5 were measured in 134 patients with definite inflammatory
      rheumatic diseases (IRD) using a sandwich type ELISA. 94 patients suffered from
      erosive IgM-rheumatoid factor positive rheumatoid arthritis (RA+), 20 with
      undifferentiated seronegative polyarthritis, 12 with osteoarthropathia psoriatica
      and psoriasis vulgaris, 3 with systemic lupus erythematosus, 3 with scleroderma
      and 2 with reactive arthritis. Elevated serum levels (> 58 ng/ml to 221 ng/ml;
      median: 93 ng/ml) were only detected in 54/94 (57%) patients with RA+, but not in
      other IRD. They correlated with advanced stages of disease (Steinbrocker stages
      III + IV; p < 0.05), elevated CRP-levels (p < 0.01) and higher measurements of
      IgM rheumatoid factor.

PMID- 9150808
TI  - CT in simple partial seizures in children: a clinical and computed tomography
      study.
AB  - INTRODUCTION: Therapeutic relevance of computed tomography (CT) in children with
      simple partial seizures (SPS) is reported to be remarkably low (1-2%). There are
      not studies, however, from the developing countries where neuroinfections are
      among important causes of seizures. The present study from India is aimed at
      evaluating the significance of CT in the management of SPS in children and to
      determine the difference in clinical features of children with and without focal
      brain lesions in CT. PATIENTS AND METHODS: CT scans of all patients aged 15 years
      of younger with SPS, seen over a period of 15 months, were reviewed. The clinical
      features of the patients with focal lesions in the CT were compared with those of
      children without focal abnormalities. RESULTS: Focal structural lesions were
      present in 117 (59.09%) of 198 children. These included: solitary contrast
      enhancing CT lesion-16.16%, focal calcification-12.12%, cysticerosis-10.10%,
      focal atrophy-9.59%, tuberculoma-6.56% and infarction-6.06%. Neuroinfections or
      their sequelae were responsible for seizures in 89 children (44.94%). There were
      no statistically significant differences in clinical features of patients with
      and without focal lesions in CT. CONCLUSIONS: CT study in children with SPS in
      developing countries has significant therapeutic relevance. It is not possible to
      clinically differentiate children with focal lesions from those without focal
      lesions in CT.

PMID- 9150807
TI  - A quantitative study of daytime sleepiness induced by carbamazepine and add-on
      vigabatrin in epileptic patients.
AB  - INTRODUCTION: The clinical relevance of daytime sleepiness associated with
      carbamazepine (CBZ) and vigabatrin (VGB) was objectively assessed by the multiple
      sleep latency test (MSLT) and nocturnal sleep recordings. MATERIAL AND METHODS:
      Twenty-six patients with partial epilepsy and mean monthly seizure frequency of
      4, aged 18 to 48 years, receiving chronic monotherapy with CBZ and subsequent VGB
      addition for 2 months (14 patients), were compared with a group of healthy
      subjects. Subjective daytime sleepiness was complained by 13 patients on CBZ
      monotherapy and 9 patients during VGB add-on treatment. RESULTS: No differences
      in nocturnal sleep parameters, but significantly shorter daytime sleep latencies
      at the MSLT, were detected in CBZ-treated patients as compared with healthy
      controls. Addition of VGB therapy did not further enhance objective daytime
      sleepiness. CONCLUSION: Some sleepiness occurs in chronically CBZ-treated
      epileptic patients, which can be objectively measured by the MSLT, but it is not
      aggravated by add-on VGB.

PMID- 9150809
TI  - The influence of clinical relapses and steroid therapy on the development of Gd
      enhancing lesions: a longitudinal MRI study in relapsing-remitting multiple
      sclerosis patients.
AB  - Fifty-three patients with relapsing-remitting multiple sclerosis who had monthly
      Gd (gadolinium) enhanced MRI (Magnetic Resonance Imaging) and clinical
      evaluation, were divided into two subgroups: 1) patients with a clinical relapse,
      treated with IVMP (intravenous methylprednisolone) and at least one enhancing
      lesion on MRI. 2) patients who did not have a clinical relapse but with at least
      one enhancing lesion on MRI. In group 1, we evaluated the number and volume of
      enhancing lesions on the scan before and three scans after IVMP therapy; in group
      2, we considered the first scan with enhancing lesions and the subsequent three
      scans. The mean number and volume of enhancing lesions on the first scan was
      significantly higher in patients with clinical relapse compared to patients
      without clinical relapse. In group 1, we found a consistent reduction in the
      first scan following steroid treatment which returned to initial levels at the
      following scan. Both volumetric and numerical evaluation are appropriate MRI
      outcome measures in monitoring therapeutic trials.

PMID- 9150810
TI  - Serum sAPO-1/Fas levels in multiple sclerosis.
AB  - Soluble APO-1 (sAPO-1) may prevent apoptosis of lymphocytes induced by activation
      of the APO-1/Fas receptor. OBJECTIVES: To determine sAPO-1 levels in the serum of
      multiple sclerosis (MS) patients and controls in order to investigate if abnormal
      lymphocyte apoptosis occurs in this disease. METHODS: Serum samples from patients
      with MS, other neurological diseases, systemic lupus erythematosus and healthy
      controls were determined by enzyme-linked immunosorbent assay. RESULTS: We did
      not detect differences in mean serum sAPO-1 levels between patients with multiple
      sclerosis and controls. CONCLUSIONS: This preliminary study suggests that
      resistance of peripheral blood lymphocytes to apoptosis mediated by sAPO-1 is not
      likely to be a major factor in the development of autoreactive cells in MS.

PMID- 9150811
TI  - Selegiline as the primary treatment of Parkinson's disease--a long-term double
      blind study.
AB  - INTRODUCTION: To assess the therapeutic efficacy of selegiline combined with
      levodopa in the long-term treatment of Parkinson's disease (PD). MATERIAL AND
      METHODS: A randomized, prospective, double-blind study on 44 patients with PD
      needing levodopa therapy after the initial double-blind treatment with placebo or
      selegiline was carried out. The patients were followed-up for 5 years under
      combination therapy. RESULTS: Selegiline induced a significant (P < 0.001)
      slowing in the need to increase the daily levodopa dose in order to compensate
      for the progression of the disease. After 5 years of combination therapy the mean
      dose of levodopa was on average 320 mg lower in the selegiline group (405 +/- 59
      mg vs 725 +/- 78 mg). The difference in the levodopa doses between the two groups
      increased along with follow-up time, as also the ratio of the levodopa doses
      (placebo/selegiline group). The number of daily levodopa doses needed to
      compensate for the occurrence of motor fluctuations was significantly lower in
      the selegiline group. The parkinsonian disability did not differ between the two
      groups because the clinical condition was kept as optimal as possible by
      adjusting the levodopa dosage. Nine patients in the placebo group needed
      initiation of additional dopaminergic therapy in comparison to one in the
      selegiline group (P = 0.004). During the 5-year follow-up period 11 patients were
      withdrawn from the selegiline group, 7 due to adverse events. There was no
      difference in mortality between the two groups. CONCLUSIONS: Selegiline therapy
      offers beneficial long-term effets in the treatment of PD.

PMID- 9150812
TI  - Regional measurements of NO formed in vivo during brain ischemia.
AB  - Nitric oxide formed in vivo in the rat brain regions of hippocampus, striatum,
      neocortex and cerebellum was spin trapped and measured ex vivo by cryogenic
      electron paramagnetic resonance spectroscopy. In non-ischemic control animals the
      rate of nitric oxide (NO) formation in the individual brain regions ranged from
      15 to 42 pmol.g-1.min-1. During exposure to global ischemia for 7 min the
      generation of NO increased in all parts of the brain. In the hippocampus the rate
      of NO formation during ischemia increased by 6-fold from a control rate of 19
      pmol.g-1.min-1. This increase was attenuated 47% by pretreatment with the NO
      synthase antagonist 7-nitroindazole, whereas pretreatment with the non-NMDA
      receptor anatogonist NBQX and the Ca2+ channel blocker NS638 did not influence
      the NO formation. The data show that short-duration ischemia elicits a
      significant, NO-synthase-dependent formation of NO in all brain regions.

PMID- 9150813
TI  - Neuropsychological deficits in adults with neurofibromatosis type 1.
AB  - OBJECTIVES: To examine neuropsychological deficits in adults with
      Neurofibromatosis type 1 (NF1) with and without an affective mental disorder
      (i.e. dysthymia). MATERIAL AND METHODS: Seventy adult NF1 patients were followed
      up after a 12-year period. Of 65 patients assessed earlier with the Comprehensive
      Psychopathological Rating Scale (CPRS), 19 patients had died. The remaining
      patients were assessed by the CPRS with the exception of 4 patients, and were
      psychiatrically diagnosed according to DSM III-R. Twelve patients were excluded
      because of advanced age, and psychiatric illness other than affective disorder.
      The remaining 30 NF1 patients (7 with affective disorder and 23 psychiatrically
      healthy), and a control group of 23 normal adults were assessed on a variety of
      neuropsychological tests. RESULTS: Results indicated NF1-related deficits in
      inductive reasoning, visuoconstructive skill, visual and tactual memory, logical
      abstraction, coordination, and mental flexibility, although basic motor speed and
      vocabulary were not affected by NF1. An affective disorder exacerbated the
      neuropsychological deficits associated with NF1 only with regard to tests
      assessing motor functions. CONCLUSIONS: NF1 results in a relatively global
      cognitive impairment among adults, and additional depressive symptoms appear to
      slow down basic motor processes. It was speculated that the NF1-related cognitive
      deficits may partly result from white-matter lesions in subcortical brain areas,
      due to proliferation of glial tissue, aberrant myelination or hamartomas.

PMID- 9150814
TI  - Impotence and nerve entrapment in long distance amateur cyclists.
AB  - OBJECTIVES: To assess the frequency and duration of symptoms suggesting
      peripheral nerve compression after long distance cycling. MATERIAL AND METHODS: A
      questionnaire based cross sectional study among 260 participants in a Norwegian
      annual bicycle touring race of 540 km. RESULTS: Thirty-five of 160 responding
      males (22%) reported symptoms from the innervation area of the pudendal or
      cavernous nerves. Thirty-three had penile numbness or hypaesthesia after the
      tour. In 10, the numbness lasted for more than one week. Impotence was reported
      by 21 (13%) of the males. It lasted for more than one week in 11, and for more
      than one month in three. Both genital numbness and impotence were correlated with
      weakness in the hands after the ride, a complaint reported by 32 (19%) of all 169
      respondents. Forty-six cyclists (30%) indicated paraesthesia or numbness in the
      fingers, half of them from the ulnar nerve area only. CONCLUSION: The frequency
      of impotence, numbness of the penis, hand weakness and sensory symptoms from the
      fingers in bicycle sport may be higher than hitherto recognized. It afflicts both
      experienced cyclists and novices. In some, the complaints may last up to eight
      months. Besides changing the hand and body position on the bike, restricting the
      training intensity, and taking ample pauses may also be necessary in prolonged
      and vigorous bicycle riding to prevent damage to peripheral nerves.

PMID- 9150815
TI  - Parainfectious myelitis: three distinct clinico-imagiological patterns with
      prognostic implications.
AB  - Seventeen parainfectious myelitis patients were studied for site, extent and
      severity of lesions. Three patterns were observed each having distinct clinical,
      electrophysiological and MRI features: 1) focal segmental myelitis--focal cord
      lesion with long tract signs and good prognosis; 2) ascending myelitis-
      continuous lesion from conus to mid-cord with upper and lower motor neuron signs
      (not necessarily spinal shock), dysautonomia and poor outcome; 3) disseminated
      myelitis--discrete lesions scattered throughout the cord with subtle signs in
      spinal segmental distribution, above and below the transverse level and moderate
      outcome. Severe autonomic dysfunction, denervation of paraspinal muscles, "dense"
      lesion on imaging and often (but not always) the absent somatosensory evoked
      potentials carried poor outcome. In conclusion "parainfectious myelitis" is a
      better term to describe transverse myelitis, as the lesion extends to a large
      vertical extent. Further classification into 3 subgroups may improve
      understanding of anatomical and physiological dysfunction and prediction of
      outcome.

PMID- 9150816
TI  - Adverse effects in epilepsy therapy. Wait and see or go for it?
AB  - OBJECTIVES: Attention for adverse effects (AEs) is important for optimizing
      epilepsy treatment. However, a uniform strategy is lacking. In particular there
      appears to be a dichotomy between those who "wait and see" and those who "go for
      it", i.e. routinely check a list of AEs. Our intention is to identify the effects
      of different approaches. METHODS: Trial reports on carbamazepine or valproate
      monotherapy (Medline-search), and data from the Nijmegen Epilepsy Research Group
      were analyzed. RESULTS: Analysis suggests that for certain AEs, such as diplopia,
      dysarthria, affect and mood disturbances, headache, dizziness, gastro-intestinal
      disturbances, dermatological disturbances and idiosyncratic reactions, it does
      not matter which approach is chosen. However, sedation, cognitive impairments,
      sexual dysfunction, hair changes, nystagmus, gait disturbances, tremor and weight
      changes are reported more frequently when routinely checked. The value of routine
      laboratory monitoring is, however, questioned. CONCLUSIONS: Use of different
      strategies to detect AEs obstructs estimation of risks of AEDs. Baseline
      measurements and regular checking for those AEs, which are reported more
      frequently by authors who actively search for AEs, is advisable.

PMID- 9150817
TI  - Review of research on the clinical presentation of acquired childhood aphasia.

PMID- 9150818
TI  - Partial remission in depressive disorders.
AB  - Although the concept of partial or incomplete remission from depression has been
      noted in the literature for many decades, it is only recently that a precise
      definition of partial remission has been formulated (1). This paper reviews
      publications relating to this concept, in terms of prevalence, clinical
      characteristics and implications for prognosis. There have been too few studies
      to allow conclusive evidence to be presented, but partial remission may affect
      one third of subjects treated for depression, and may increase the risk of
      further depressive relapse and adversely affect social and work performance. This
      paper highlights the need to increase awareness of this concept among clinicians
      so that residual symptoms may be aggressively treated, and also comments on the
      need for researchers to consider this important group in all treatment and
      outcome studies.

PMID- 9150819
TI  - Severity of alcohol dependence and its relationship to neurological soft signs,
      neuropsychological impairment and family history.
AB  - We examined the relationship between severity of alcohol dependence, subtle
      neurological impairment, neuropsychological deficits and genetic vulnerability
      among 36 day hospital attenders who satisfied the DSM-III-R criteria for alcohol
      dependence. Severity of alcohol dependence was unrelated to the presence of a
      family history, but was correlated with neurological soft signs and
      neuropsychological impairment. Neurological soft signs were correlated with
      neuropsychological impairment on both Trail A and Trail B. Patients with an
      affected first-degree relative exhibited more neurological soft signs. These data
      indicate that severity of alcohol dependence is related not only to
      neuropsychological impairment, but also to subtle neurological deficits which may
      not be apparent on conventional neurological examination. Patients with a
      positive family history of alcohol dependence may be particularly susceptible to
      the neurological sequelae of alcohol dependence, or may have neurological
      deficits which antedate their alcohol dependence.

PMID- 9150820
TI  - Beck's Depression Inventory as a screening instrument for adolescent depression
      in Sweden: gender differences.
AB  - Beck's Depression Inventory was administered in a study of all students aged 16
      17 years in the first year of high school in a Swedish town, and was completed by
      93% of them (n = 2270). Cronbach's reliability coefficient alpha was 0.89, and
      there were strong correlations between item scores and total scores. A diagnostic
      interview focused on depressive diagnosis during the last year was conducted with
      88% (n = 199) of all students with high scores (> or = 16), and with the same
      number of controls with low scores. A depressive diagnosis was confirmed in 73%
      of high scorers and 13% of low scorers. The questionnaire performed better with
      girls than with boys. The mean score was significantly higher for girls, and the
      proposed limit for moderate depression (a score of 16) was reached by 14.2% of
      girls and 4.8% of boys. All symptoms were significantly more frequent and more
      severe in girls. It was found that 20% of girls and 6% of boys reported suicidal
      ideation. In a factor analysis the strongest factor that emerged differed between
      the sexes. For boys it included sadness, crying and suicidal ideation, and for
      girls it included failure, guilt, self-dislike and feeling unattractive, combined
      with suicidal ideation. The gender differences are discussed.

PMID- 9150821
TI  - Drugs taken in fatal and non-fatal self-poisoning: a study in south London.
AB  - This study compared the number and type of substances taken in deliberate self
      poisoning with fatal (n = 127) and non-fatal (n = 521) outcome. The aims were (i)
      to describe substances typically involved in self-poisoning in England and Wales,
      (ii) to examine the role of drug "cocktails' and (iii) to examine whether toxic
      substances are over-represented in cases with fatal outcome. Over-the-counter
      (OTC) analgesics, minor tranquillizers and antidepressants accounted for about
      70% of substances taken, irrespective of outcome. Compared with survivors, cases
      who died had taken a higher mean number of substances. Among self-poisonings with
      a single substance, antidepressants and paracetamol-opiate combinations were over
      represented in fatal-outcome cases. This report emphasizes the role of OTC
      analgesics and antidepressants in overdose-related mortality in England and
      Wales.

PMID- 9150822
TI  - Dose escalation vs. continued doses of paroxetine and maprotiline: a prospective
      study in depressed out-patients with inadequate treatment response.
AB  - In view of the fact that controlled prospective studies on the benefits of dose
      escalation of the selective serotonin re-uptake inhibitor (SSRI) paroxetine are
      lacking, we conducted a double-blind, randomized, parallel-group multicentre
      study designed to compare the possible benefits of dose escalation of paroxetine
      and maprotiline in patients suffering from major or minor depression according to
      modified Research Diagnostic Criteria (RDC) with inadequate treatment response.
      The study sample consisted of 544 out-patients with different degrees of severity
      of depression. Patients received either 20 mg paroxetine (n = 271) or 100 mg
      maprotiline (n = 273) for the first 3 weeks in a double-blind manner. Response
      after 3 weeks was defined using explicit operationalized criteria. Patients with
      inadequate treatment response (paroxetine group, n = 86; maprotiline group, n =
      88) were again randomized to either continuation of the previous dosage
      (paroxetine, n = 36; maprotiline, n = 48) or increased doses, i.e. 40 mg
      paroxetine (n = 50) or 150 mg maprotiline (n = 40), respectively. Intention-to
      treat and completer analyses were performed. Defining response as a reduction in
      Hamilton Depression Rating Scale (17-item version) (HAMD-17) score of at least
      50% from baseline, no significant benefits of dose escalation were found for
      either paroxetine or maprotiline. Stratification according to baseline severity
      of depression also revealed no significant benefits of dose escalation. After
      dose escalation, new adverse events that had not been present during treatment
      with lower doses rarely occurred. Our results support the view that a dose of 20
      mg paroxetine is optimal for the acute treatment of depression in the majority of
      patients.

PMID- 9150824
TI  - Overcoming resistance to exposure in panic disorder with agoraphobia.
AB  - The issue of panic disorder resistant to treatment (whether pharmacological or
      psychological) has attracted little research attention, despite its clinical
      frequency and importance. The aim of this study was to compare three treatment
      modalities, namely exposure alone (E), exposure associated with imipramine (EI)
      and cognitive therapy supplementing exposure (EC), in a sample of 21 patients
      with DSM-IV panic disorder and agoraphobia, who failed to respond to a first
      standard course of individual behavioural treatment based on exposure in vivo.
      Treatments were administered according to a cross-over, controlled design (E-EI
      EC, EI-EC-E, EC-E-EI). Twelve of the 21 patients achieved remission (panic-free
      status) during the trial. In 8 cases this occurred after exposure alone (E) and
      in two cases each after the other treatments (EI and EC). The results revealed a
      significant effect of the factor time on a number of variables, and the
      superiority of exposure alone compared to other treatment modalities with regard
      to some variables. These findings suggest that long-term behavioural treatment
      based on exposure may be necessary in some patients, and may induce clinical
      remission. However, patients who do not respond to exposure show poor tolerance
      of and compliance with pharmacological treatment, and are unlikely to achieve
      remission with imipramine or cognitive therapy, even though this may occur in
      individual cases.

PMID- 9150823
TI  - Differences between urban and rural suicides.
AB  - As part of a nation-wide psychological autopsy we examined the differences in DSM
      III-R mental disorders, recent life events and other characteristics between
      urban (n = 143) and rural (n = 85) completed suicides in a random sample of 229
      cases from the National Suicide Prevention Project in Finland for the period 1987
      1988. Psychoactive substance use disorders (48% vs. 34%), cluster B personality
      disorders (24% vs. 9%) and psychiatric comorbidity (66% vs. 42%) were found more
      commonly among urban than rural suicides. Urban suicides were also more often
      reported to be preceded by a recent separation (25% vs. 8%), whereas rural
      suicide victims tended to have lacked a close companion of the opposite sex (36%
      vs. 18%) and to have had physical disorders (56% vs. 40%). Overall, urban and
      rural suicides may vary with regard to the prevalence of some mental disorders,
      their comorbidity, and physical disorders, as well as the preceding life
      situation. This variation may also imply the need for differences in strategies
      for suicide prevention in each setting.

PMID- 9150825
TI  - Mental illness, physical abuse and burden of care on relatives: a study of acute
      psychiatric admission patients.
AB  - As mental health care policies increasingly emphasize treatment and care in
      community settings, there has been concern over the burden that families of
      mentally ill people might suffer as a result. We conducted a study of the
      prevalence of abuse faced by relatives of patients admitted during a 6-month
      period to the acute psychiatric unit of a busy general hospital, who had
      previously been living with a relative. Patients and their relatives were
      assessed using semi-structured interview schedules. The experience of burden and
      the specific experiences of abuse since the onset of their relative's illness
      were recorded. In total, 32 (32%) of the 101 relatives had been struck on at
      least one or two occasions. Verbal abuse, threats and temper outbursts were
      reported by over 50% of the relatives. Principal correlates of abuse were
      diagnosis, concurrent drug misuse and a poor pre-morbid relationship between
      carer and patient.

PMID- 9150826
TI  - Criminal and psychiatric histories of Finnish arsonists.
AB  - We investigated psychiatric and demographic variables and lifetime criminality
      among arsonists referred for a pre-trial psychiatric assessment. The medical and
      criminal records of 282 arsonists were studied in order to compare first-time and
      repeat offenders with regard to diagnostic, demographic and biological variables.
      Alcohol dependence and antisocial personality disorder were common among
      recidivist offenders. This finding was especially prominent among offenders who
      committed violent crimes. Recidivist offenders commonly had a history of long
      lasting enuresis during their childhood. They were younger at the time of their
      first offence, and were more often intoxicated with alcohol during the arson
      attempt. Among arsonists, lifetime criminal recidivism was primarily associated
      with alcohol dependence and antisocial personality disorder. Psychosis was a
      common diagnosis among subjects who had no record of recidivist criminal
      offences.

PMID- 9150827
TI  - The prevalence of current major depression and dysthymia in a Norwegian general
      practice.
AB  - Existing studies suggest that depression is underdiagnosed and undertreated in
      general practice, and that the known prevalence of this mood disorder in a
      primary care population may represent only the "tip of the iceberg'. A total of
      100 consecutive patients in an average Norwegian general practice were tested, of
      whom 31 patients were diagnosed as having a depressive illness in this study; 28
      patients were diagnosed as having current major depression and three as having
      dysthymia. In total, 21 of the 28 patients with current major depression
      presented with other symptoms as their major complaints at the consultation in
      which they were tested. Twelve of these 21 patients had some kind of pain
      problem.

PMID- 9150828
TI  - Relationships between characteristics of the ward atmosphere and treatment
      outcome in a psychiatric day-care unit based on occupational therapy.
AB  - The relationships between characteristics of the ward atmosphere and treatment
      outcome in a psychiatric day-care unit were investigated. The treatment programme
      was based on occupational group therapy and included long-term mentally ill
      patients, equally distributed with regard to psychosis and non-psychosis
      diagnoses. The ward atmosphere was rated on the Community-Oriented Programs
      Environment Scale (COPES), and outcome variables concerned symptoms, global
      mental health, quality of life, and functioning in daily life. The COPES ratings
      were re-coded in order to control for the fact that different levels of ward
      atmosphere factors are recommended for psychotic and non-psychotic patients. The
      results revealed that an optimal initial level of anger and aggression in
      treatment was significantly associated with improvement in global mental health
      and functioning in everyday life. Initial optimal levels of staff control and
      practical orientation were significantly associated with improvement in
      psychiatric symptoms. The characteristics of the ward atmosphere at the end of
      the treatment period were significantly correlated with various aspects of
      functioning in daily life. The study demonstrated associations with outcome
      variables not previously linked with ward atmosphere characteristics, e.g.
      functioning in daily life and quality of life.

PMID- 9150829
TI  - Personality and personality disorders predict development and relapses of major
      depression.
AB  - The aim of this study was to investigate the role of personality deviations in
      the development and relapses of major depression. The study is based on an
      investigation of an initial sample of 298 psychiatric out-patients, who were re
      evaluated after 6 years when the sample included 253 patients. SCID-R was used
      for assessment of possible relapses and new cases, and a logistic regression
      analysis was used to determine the best prediction of the recurrence of
      depression. Borderline personality disorders and dependency predicted relapses.
      In addition, borderline personality disorders, together with avoidant personality
      disorders, predicted the development of new cases. Comorbid clinical syndromes
      appear to be of no importance. These findings suggest that the comorbidity with
      personality deviations accounts for the chronicity and poor prognosis in major
      depression.

PMID- 9150830
TI  - A two-phase, double-blind randomized study of three haloperidol plasma levels for
      acute psychosis with reassignment of initial non-responders.
AB  - To clarify the plasma level/therapeutic response relationship of haloperidol
      (HPDL) we used a prospective double-blind design in 95 acutely psychotic
      patients. After drug washout, patients were randomly assigned to a low, middle or
      high plasma level range for 2 weeks (phase A), and then 50% of the initial non
      responders were randomly reassigned into the putative therapeutic range for an
      additional 2 weeks (phase B). There were no significant differences in clinical
      outcome between the three plasma level ranges in phase A. However, in phase B
      initial non-responders displayed greater improvement in the middle range than in
      the low or the high ranges. No further benefit was observed when plasma levels
      were raised to or maintained in the high range.

PMID- 9150831
TI  - Development and validation of a computerized screening test for personality
      disorders in DSM-III-R.
AB  - The available self-report instruments designed to measure personality disorder
      (PD) are time-consuming to administer and/or score and can be impractical for
      routine clinical use. There is a need for a computerized method of personality
      assessment based on contemporary systems of classification. A computerized DSM
      III-R-based questionnaire was developed and validated against the structured
      clinical interview for DSM-III-R Axis-II disorders on a sample of 60 subjects.
      The computerized test showed moderate validity as a diagnostic instrument (mean
      kappa coefficient = 0.47). With adjusted cut-off scores it was valid as a
      screening instrument (mean sensitivity = 0.87). Antisocial, borderline and
      avoidant PD scores were strongly correlated across measures and not subject to
      significant observer bias.

PMID- 9150832
TI  - The importance of a differentiated psychopathology of catatonia.

PMID- 9150833
TI  - Thymus hyperplasia, differential diagnosis in the wheezing infant.
AB  - Thymus hyperplasia is not a rare condition in infancy, but it is generally
      considered not to cause any symptoms. We present here a series of 11 children
      seen at the National Institute of Pediatrics (NIP), Mexico-city, that do have
      respiratory symptoms secondary to the enlarged gland. Age of onset of the
      symptoms was median at birth, with age of first visit to the NIP of 6 months.
      Symptoms were respiratory crisis and various respiratory complaints. Five
      underwent thoracotomy and resection of the right pulmonary lobe was necessary in
      one, because of irreversible changes in the lung tissue due to chronic
      compression. In another patient thymic lobectomy was executed because extrinsic
      compression of the right upper bronchus resulted in recurrent atelectasia. The
      five biopsies taken during the intervention showed normal or hyperplastic or
      involutive thymic tissue without signs of malignancy. The evolution was positive
      in all the patients. In conclusion thymic hyperplasia must be taken into account
      in the evaluation of an infant with respiratory symptoms.

PMID- 9150834
TI  - Performance of a fully automated in vitro allergy testing system.
AB  - BACKGROUND: Since the development of the radioallergosorbent test (RAST) for
      quantification of allergen-specific IgE, numerous non-radoisotopic methods have
      been devised which combine the proven cellulose disc technology with enzyme
      linked immunoassay methods. The HY.TEC EIA (Hycor Biomedical, Inc. Irvine, CA)
      was compared with Pharmacia CAP with respect to overall system features and assay
      performance characteristics. METHODS: The HY.TEC EIA and Pharmacia CAP were
      compared with respect to calibrator range, sensitivity, type of detection, type
      of solid phase, throughput, and mode of operation. To determine the assay
      sensitivity and specificity for a variety of allergens, a total of 2,447 tests
      were performed on both CAP and HY.TEC EIA. The samples were scored positive in
      both cases using a cutoff of 0.35 IU/mL. RESULTS: The general features of the
      HY.TEC EIA system are comparable to Pharmacia UniCAP, with the added advantage of
      higher throughput. Intra-assay precision was 7% and inter-assay precision was 9
      15%. Using CAP as a comparative method, HY.TEC EIA has a sensitivity of 94.0% and
      a specificity of 94.4%. CONCLUSIONS: The HY.TEC EIA demonstrates excellent
      agreement with the Pharmacia CAP system in the determination of allergen-specific
      IgE. With the automation necessary in today's clinical laboratory, we conclude
      that the HY.TEC EIA is a state-of-the-art tool for the diagnosis of allergic
      disease.

PMID- 9150835
TI  - Clinical tolerance, parasitological efficacy and environmental effects of
      dehumidifiers in stable asthmatics sensitized to house dust mites.
AB  - Dehumidifiers (DH) are potentially effective appliances as coadjuvant therapy in
      the treatment of bronchial asthma caused by sensitization to house dust mites.
      The aims of this study were to analyze DH tolerance in asthmatic patients, to
      assess the parasitological effects and to analyze the environmental effects
      produced by the use of these appliances in the bedrooms of asthmatic patients
      sensitized to house dust mites. 10 stable asthmatic patients sensitized to house
      dust mites were studied. DH appliances (CD-300) were installed in their bedrooms.
      Each patient was given symptom scoring tables and a portable peak expiratory flow
      (P.E.F.) during a period of 5 months, 1 month before installing the DH and 4
      months afterwards. To study the parasitological efficacy of the DHs, we analyzed
      dust samples from the bedrooms and determined the Der p I, Der f I and Der II
      allergens by means of a modified ELISA based on monoclonal antibodies. Dust
      samples were collected before installing the DHs and after they had been working
      for 2 and 4 months. Dry temperature and relative humidity measurements at three
      time intervals (7-9, 15-17 and 22-24 h) were carried out. The 1st measurement was
      done prior to installation of the DHs in the patients' bedrooms and the 2nd and
      3rd were achieved 2 and 4 months respectively after the installation. Statistical
      analysis was done by comparison of paired means. No significant differences were
      detected in the patients' symptoms nor in the P.E.F. measurements in the course
      of the study. Decreases in the house dust mite allergens were observed in 4
      bedrooms. A significant decrease in relative humidity in the bedrooms of mite
      asthma patients after use of dehumidifier appliances was observed (p < 0.01).
      Significant differences between the measurements of the bedrooms with and without
      DH were detected (p < 0.01). In summary, DHs were well tolerated by stable
      asthmatic patients, produced a significant decrease in the relative humidity
      level and showed some parasitological efficacy.

PMID- 9150836
TI  - In vitro IgE synthesis in neonates with different family history of atopy.
AB  - In this study we want to correlate family history of atopy and in vitro synthesis
      of IgE, IL4 and IFN gamma in 5 neonates with biparental (group A), 5 with
      uniparental (group B) and 5 with absent family history of atopy (group C). An
      aliquot of neonatal blood mononuclear cells (NBMC) was incubated in presence of
      PHA in combination with the phorbol ester acetate (TPA). The supernatants of
      cultures were harvested after 48-72 hours of incubation and stored at -20 degrees
      C until testing for lymphokine production by ELISA kits. Only one neonate of
      group B showed detectable in vitro synthesis of IL4 (45 pg/ml) after PHA + TPA
      stimulation. All the others failed to produce detectable levels either of IL4 or
      IFN gamma. Another aliquot of NBMC was cultured in the presence of saturating
      concentrations of rhIL4 for 48 h. After this pre-incubation step, the non
      adherent cells were cultured in the presence of: 1) rhIL4; 2) rhIL4 + anti-IL4
      antibody (Ab); 3) rhIL4 + anti-IFN gamma Ab; 4) rhIFN gamma, 5) rhIFN gamma +
      anti-IFN gamma Ab + rhIL4; 6) PWM + rhIL4; 7) unstimulated culture. The
      supernatants of these cultures were tested for their IgE content. In general,
      spontaneous IgE production by NBMC was very low, rhIL4 did not induce a
      significant increase of IgE synthesis. The other modalities of stimulations did
      not produce significative changes. We did not observe significative differences
      among the three groups of neonates. On the basis of our results, we conclude that
      NBMC aren't able to produce significative amounts of IgE in vitro either
      spontaneously or after IL4 stimulation. This test and the evaluation of IL4 and
      IFN gamma in vitro production aren't useful markers of atopy predisposition.

PMID- 9150837
TI  - Prevalence of atopy in young healthy population, in Izmir, Turkey.
AB  - The aim of this study was to determine the prevalence of atopy especially in
      young aged group in which allergic diseases are frequently seen. We carried out
      this study in Izmir which is located on the west coast of Turkey and has all the
      characteristics of mediterranean climate. However, we evaluated whether
      geographical characteristics such as climate, dampness, kinds of plant might be
      affected on prevalence of atopy. Participants were randomly selected and detailed
      standard questionnaire about if they or their relatives had any allergic symptoms
      were applied. The skin prick tests (SPT) with standardzied allergen extracts were
      performed and serum total IgE levels were assayed. The study group consisted of
      277 individuals, aged 15-25 years. Based on the questionnaire, 123 (44.4%)
      participants described positive history of atopy. In 127 of 277 subjects (46%)
      was found at least one positive skin-test response and the most frequent allergen
      was house-dust mites. SPT was positive in 68 (55.2%) of 123 subjects who had
      atopic history and in 59 (38%) of 154 subjects who had negative history of atopy.
      The subjects who had atopic history showed more frequently positive SPT
      prevalence than the others (p < 0.01). Geometric mean of total IgE level was
      105.5 kU/L in SPT positive 127 subjects and 57.7 kU/L in SPT negative 150
      subjects. There was a positive relationship between total IgE level and positive
      SPT (p < 0.01). History of atopy was correlated with total IgE levels in males (p
      < 0.01) but not in females. Women more often than men reported atopic history in
      the absence of true atopy.

PMID- 9150838
TI  - Comparative study of inhaled amiloride and inhaled furosemide in exercise-induced
      asthma.
AB  - BACKGROUND: Certain diuretics such as furosemide, when inhaled, have been found
      to be useful in preventing Exercise-Induced Asthma (EIA). STUDY OBJECTIVE: To
      assess the possible preventive effect of inhaled amiloride in EIA. DESIGN: A
      double blind, randomized, cross-over study comparing the effect of inhaled
      amiloride, inhaled furosemide and placebo in EIA. PATIENTS: Sixteen asthmatic
      patients (8 males and 8 females) with an average age of 21 years (range 9-31) who
      presented a FEV1 decrease of over 15% in a previous free-running exercise test.
      INTERVENTIONS: Solutions were inhaled with a Hudson nebulizer connected to an
      oxygen source in different days before exercise testing. A Vitalograph Compact
      (Ohmeda, England) spirometer was used and FEV1 was obtained at baseline, three
      minutes after solution inhalation, immediately after exercise and then every 5
      min. until 20 minutes post-exercise. The changes in FEV1 percentages (FEV1%) and
      the mean FEV1 decreases expressed as percentages for each solution were compared.
      RESULTS: Inhaled furosemide diminished the fall in the FEV1 at every time after
      exercise. The maximum decrease in mean FEV1 was at 5 minutes post-exercise and
      was 11 +/- 7% with furosemide, 24 +/- 14% (p < 0.01) with amiloride and 19 +/-
      12% (p < 0.05) with placebo. Amiloride administration resulted in a slight but
      significative increase in the FEV1 fall (p < 0.01 when compared with placebo).
      CONCLUSIONS: Amiloride is not useful to protect EIA whereas Furosemide does it.
      These differences results may be related to the differents mechanisms of action
      of the two diuretics.

PMID- 9150839
TI  - Nasal hypersensitivity in purulent middle ear effusion.
AB  - The existence of a physiopathologic connection between nose and middle ear is
      widely accepted so that chronic purulent middle ear effusion (CPMEE) could be
      expected to be usually associated with nasal chronic disease or impaired
      function. Nevertheless such association is less frequently observed in clinical
      practice than one could expect, possibly because of inadequate nasal function
      evaluation. Thirty-five patients affected by CPMEE were included in this study in
      order to assess the incidence of nasal disorders. E.N.T. clinical history was
      obtained and E.N.T. physical examination, nasal endoscopy by fiber optics,
      anterior rhino-rheo-manometry, non-specific nasal provocation test with
      histamine, mucociliary transport test, and allergic skin tests were performed. In
      the clinical history assessment 26 patients were affected by chronic
      rhinopathies, 16 by chronic pharyngitis, and 20 by frequent headache. At
      rhinoscopy we registered nasal septum deviation in 24 cases and mean and inferior
      turbinates hypertrophy in 31 cases. CPMEE and nasal septum deviation or
      turbinates hypertrophy were more frequently ipsilateral (p < .001 and p < .05,
      respectively). Total nasal resistance was 0.99 +/- 0.49; it was abnormally high
      in 11 subjects bilaterally and in 4 subjects monolaterally and increased
      significantly in 32 patients following nasal provocation test. Mucociliary
      transport time was longer in CPMEE subjects than in 10 healthy subjects (18 +/- 5
      vs 13 +/- 4 min; p < .05). Finally 10 patients presented positive skin tests. On
      the whole, 96% of non allergic patients included in this study showed signs of
      non-specific nasal hypersensitivity which could theoretically cause purulent
      middle ear effusion to chronicize. Indeed recurrent histamine release in response
      to specific and/or aspecific stimuli could cause the obstruction of the
      Eustachian tube and consequently inadequate middle ear ventilation.

PMID- 9150840
TI  - Sensitization to Anisakis simplex: an unusual presentation.
AB  - It has recently been published patients suffering from urticaria or anaphylaxia
      induced by nematodes usually parasitizing fishs or cephalopode, in whom, Anisakis
      simplex (AK) sensitization prevalence was detected up to 37%. We tried out a
      prospective study to evaluate the presence of AK specific-IgE in an asthmatic
      population, comparing to other group of patients with urticaria. Complaints
      related to food ingestion were recorded in both, and dietetic measures were
      advised. Thirteen patients (13/66; 20%) showed AK specific IgE. Nine of them were
      asthmatics (p < 0.01), and only 4 suffered from urticaria. Four patients, three
      of them asthmatics, could link symptoms after fishs, cephalopode or,
      surprisingly, seafood intake, including epigastralgia, rhinorrhea,
      conjunctivitis, hives, and dyspnea. Atopia was not a consistent status, only five
      AK sensitized patients also did to common inhalants (all skin prick-test positive
      to house dust mites). Asthmatic AK-sensitized patients were older than non AK
      sensitized asthmatics (46.23 vs 30.1; p < 0.05). The way of sensitization could
      be inhalative or through digestive mucosa parasitization by live larvae.
      Possibility that an AK allergen can play a role in adult asthma, should be
      considered specially in countries with high fish or seafood diet content.

PMID- 9150841
TI  - Cytokine serum profiles in allergic and non-allergic asthma. Increased production
      of IL-10 by non-allergic asthmatic patients.
AB  - Studies were undertaken to determine whether differences in serum cytokine
      balances could be involved in the pathogenesis of allergic and in non-allergic
      asthma. At this propose, interferon-gamma, tumor necrosis factor-alpha,
      interleukin-2, interleukin-4, interleukin-6, and interleukin-10 were measured by
      enzimoimmunoassay. The analysis was performed on 24 allergic and 24 non-allergic
      asthmatic patients and 16 healthy subjects. IFN-gamma and TNF-alpha, included
      into the type 1 cytokines, appeared significantly increased in the allergic with
      respect to the non-allergic asthmatic patients (p = 0.01) and (p < 0.001)
      respectively, while IL-10, which belongs to the type 2 cytokines, was
      significantly increased in the non-allergic asthmatic (p < 0.001). The IL-6
      analysis did not show any significant difference in either of the study group.
      The most interesting finding was the high serum IL-10 values detected in
      intrinsic asthmatic patients, which in turn, suggests that this cytokine could
      participate in the regulation of different immunological features that occurs in
      non-allergic asthma, and maybe it could indicate a higher stimulated state of
      cells in this type of asthma. The data presented in this report show a different
      cytokine profile in serum from allergic and non-allergic asthmatic patients and
      denote a stronger prevalence of type 2 cytokines in intrinsic asthma.

PMID- 9150842
TI  - Leukotrienes and their antagonists in allergic disorders.
AB  - Cysteinyl leukotrienes are important mediators of asthma, and inhibition of their
      effects may represent a potential breakthrough in the therapy of allergic
      rhinitis and asthma. Strategies for inhibition of cysteinyl leukotriene receptors
      and inhibition of 5-lipoxygenase activity. The leukotrienes antagonists, with
      particular reference to asthma and allergic rhinitis, is reviewed in this paper.
      In studies in asthmatic patients, these compounds can inhibit bronchoconstriction
      in response to exercise, aspirin and allergen. Results from clinical studies
      using receptor antagonists, such as LY-171883, SK&F-104353, ICI-204219, ONO-1078,
      MK-751, MK-0679, demonstrate beneficial effects, with improvement in symptoms and
      forced expiratory volume in one second (FEV1), and a reduction in the use of beta
      2-adrenergic relief medication. NZ-107 was studied for its effect on airway
      inflammation caused by intratracheal injection of LTB4 or IL-5, or by inhalation
      of PAF, and by cell activation. Analysis of the BAL fluid revealed that both
      induced eosinophilia and neutrophilia were suppressed. Surprisingly, although PAF
      and superoxide generation were inhibited in macrophages and eosinophils, NZ-107
      had no effect on neutrophil activation. U-75302 was studied in guinea pigs and
      inhibited LTB4 induced chemotaxis of eosinophils in vitro and antigen-induced
      lung eosinophilia in vivo. Further studies are needed to clarify the exact
      mechanism by which these compounds provide beneficial effects.

PMID- 9150843
TI  - Molecular diagnosis of congenital bilateral absence of the vas deferens: analyses
      of the CFTR gene in 64 French patients.
AB  - Congenital bilateral absence of the vas deferens is a congenital reproductive
      disorder that affects about one in 1000 male individuals. Screening of the entire
      coding and flanking sequences of the cystic fibrosis transmembrane conductance
      regulator (CFTR) gene in 64 males with CBAVD revealed that in only 23% CBAVD was
      caused by two CFTR mutations. The 5T allele in one copy, that causes reduced
      levels of the normal CFTR protein, in combination with a CFTR mutation in the
      other copy, was one of the most common causes of CBAVD. Twenty six per cent of
      men with CBAVD had the 5T allele. The presence of only one CFTR mutation or the
      5T allele in 34% of patients suggests that undetected changes in CFTR may be
      involved in CBAVD. These molecular defects are probably mutations with partial
      penetrance. Moreover, the high proportion (20%) of patients with CBAVD who did
      not have CFTR mutations or the 5T allele allows to propose that another gene or
      genes could be responsible for CBAVD. In these cases, in vitro fertilization may
      be required and the genetic counselling appears to be very complex and additional
      studies, including CFTR mRNA and linkage analyses, are required to resolve these
      questions.

PMID- 9150844
TI  - Characterization of an isodicentric Y-chromosome for the long arm in a newborn
      with mixed gonadal dysgenesis.
AB  - A newborn infant was referred for evaluation because of ambiguous genitalia.
      Examination of the genitalia revealed a hypospadiac phallus measuring 1.5 cm in
      length with chordee. Subtle phenotypic features consistent with Turner syndrome
      were present including hypertelorism, anti-mongoloid slant to the eyes, mild
      widening of the neck, but no definitive webbing, shield like chest and positive
      cubitus valgus. A pelvic and renal sonogram confirmed the presence of a uterus
      and normal-appearing kidneys. There was incomplete fusion of the scrotum. No
      gonads were palpable within the scrotal sac. The patient was assigned a female
      gender on the basis of the presence of a uterus, the phenotypic appearance of the
      genitalia and the malignant potential of the gonads. The cytogenetic findings
      with QFQ-banding revealed an abnormal karyotype, i.e., mos 46,X,idic(Y)
      (p11.2)[77]/45,X[29]/46,X,idic(Y) (p11?) [2]/
      47,XY,idic(Y)(p11.2)[2]/47,X,idic(Y)(p11.2), + idic(Y)(p11.2)[1]/46,XY[1]. The
      presence of an abnormal isodicentric Y-chromosome was evaluated by FISH-technique
      to ensure a finer characterization than routine methods. The genotype-phenotype
      correlation could not be established since mosaicisms of highly variable nature
      can exhibit an unpredictable outcome.

PMID- 9150845
TI  - Agenesis of corpus callosum and anophthalmia in the asplenia syndrome. A
      recognisable association?
AB  - We present a newborn infant with the asplenia syndrome and unique associated
      features of corpus callosum agenesis, anophthalmia and coloboma. Previous reports
      of eye abnormalities or corpus callosum agenesis in patients with asplenia
      suggest that this may represent a distinct clinically recognisable entity of
      abnormal lateralisation.

PMID- 9150846
TI  - Cytogenetic characterization of interspecific somatic hybrids by PRINS.
AB  - The primed in situ (PRINS) labeling technique was developed as an alternative
      method to classical cytogenetics and in situ hybridization (FISH) for the
      characterization of interspecific somatic hybrids. Full karyotypes were performed
      using Alu specific primers generating the painting of all human material
      associated with R like banding. The representativity of individual human
      chromosomes was established using primers specific for discriminent alpha
      satellite DNA sequences providing specific signals on the centromeres of the
      targeted chromosomes and corresponding spots in interphase nuclei. Due to the use
      of synthetic oligonucleotide primers and of directly labeled haptens. PRINS
      method avoid repetitive probes preparation, eliminates secondary amplification of
      signals and the whole process can be performed within a timespan of 1 hour.
      Providing qualitative and quantitative answers, the simple PRINS method appears
      very well adapted to the specific problematic of somatic hybrids as for their
      characterization than for their periodic controls imposed by their instability.
      The method has been tested on 4 human-rodent hybrid cell lines. In particular,
      the somatic hybrid clone ALE 4 was shown to be monochromosomal for the der(11)
      from the reciprocal translocation t(11:22).

PMID- 9150847
TI  - Uniparental disomy (UPD). Genomic imprinting and a case for new genetics
      (prenatal and clinical implications: the "Likon" concept).
AB  - Uniparental disomy (UPD) is often the result of an aneuploid event masquerading
      under the features of diploidy. As such, it may never be recognized, being at 2
      opposite phenotypic poles, harmless to the bearer, or, if harmful, eventually
      responsible for uncharacteristic although perhaps serious conditions. UPD can
      also be associated with problems such as recessiveness or mosaicism. This article
      considers the chances of unmasking UPD, in the course of CVS or AC prenatal
      diagnosis, by reviewing the main cytogenetic signals and major familial or
      personal antecedents raising its suspicion. Once suspected, the lead toward UPD
      may or may not be followed through appropriate molecular studies. UPD for either
      maternal or paternal chromosomes 13, 21 and 22 may not have consistent, common
      deleterious effects, while other identified UPD's are too rare to call.
      Unconditionally, main, consistent or near consistent damages to the phenotype
      have been traced to specific chromosome pairs such as 15 mat (Prader-Willi
      syndrome), 15 pat (Angelman syndrome), 11 pat (Wiedemann-Beck with syndrome), 14
      mat and pat (multiple cogenital and developmental anomalies [MCDA]-several rather
      constant) and 7 mat (Russel-Silver [RS] and Growth-failure [GF]). The above
      problems all stem from an alteration of the normal, developmentally important
      genomic imprinting processes and most of them may recognize several
      etiopathogenic paths, other than UPD, none of which abides by straight Mendelian
      rules. In this very area, therefore, a new, non-traditional type of inheritance
      is confronting genetic counselling. In this paper, for want of appropriate
      semantic language, the neologism "likon" (or "laikon") is coined to make
      reference to the hemizygously expressed sequences of the genomic parts imprinted
      in the somatic tissues. Broadening the definition, the word is then applied to
      the 4 possible epigenotypes of imprinted domains, which depend on the parental
      sex-of-origin: germinally "resting" (R), or "acting" (A), to be made somatically
      silent, that is to say "unexpressed" (U), or transcribed and "expressed" (E),
      thus abbreviated as EA, ER, UA and UR. Entire pedigrees may then be analyzed
      accordingly in health and in disease. Examples are presented herewith.

PMID- 9150848
TI  - Prevalence, male germ-line origin and new patterns of inversions in haemophilia
      A.
AB  - Following the discovery of the FVIII gene inversion by Lakich et al. [1] and
      Naylor et al. [2], we have investigated this mutation in 108 French and Algerian
      severe haemophilia A patients. We have found that only 29 severe haemophiliacs
      (27%) exhibited the rearrangement whereas Lakich et al. [1] and Naylor et al. [2]
      respectively estimated the inversion frequency at 47% and 42% in severe
      haemophiliacs. The reason for this discrepancy is not accounted for. In this
      study, we observed two novel patterns of inversions as yet unreported. We did not
      find any correlation between the presence of the inversion and a particular RLFP
      haplotype, or ethnic origin, or the absence of a FVIII inhibitor. Among the cases
      with the inversion, the proportion of sporadic and transmitted cases was roughly
      equivalent and we also confirm that the inversion occurs preferentially in the
      male germ-line.

PMID- 9150849
TI  - A phenotypical male infant with 46,X,der(Y)t(X;Y)(?;p11) de novo.

PMID- 9150850
TI  - Collaborative study of mosaic tetrasomy 12p or Pallister-Killian syndrome
      (nineteen fetuses or children).
AB  - The difficulties in the diagnosis of Pallister-Killian syndrome are illustrated
      in this study of nineteen fetuses and children. Diagnosis based on clinical
      appearance alone is often difficult due to the broad spectrum of clinical
      anomalies not specific to this syndrome. Due to mosaicism, it is altogether
      necessary to examine several tissues for the presence of tetrasomy 12p, including
      circulating lymphocytes in which mosaicism can be as low as 1-3%, amniocytes,
      chorionic cells and skin fibro-blasts in which mosaicism ranges from 6-100%. When
      highly suspected on ultrasound examination, the diagnosis recommends prenatal
      cytogenetic studies because survivors are severely mentally retarded. All the
      cases are sporadic with only a single preliminary report of recurrence. The
      cytogenetic diagnosis is therefore helpful in order to reassure family members in
      regard to genetic counseling.

PMID- 9150851
TI  - Trisomy for the distal segment of the short arm of chromosome 17 in a boy with
      mild mental retardation and some dysmorphic features.
AB  - The authors describe a boy with a triangular face, wide forehead, telecanthus,
      large ears, prominent root of the nose, long and bulging philtrum, thin upper
      lip, everted lower lip, high arched palate, micrognathism, pointed chin,
      overriding toes, joint laxity, and mild mental retardation. Cytogenetic
      investigation disclosed the presence of an added chromosome, a very small
      acrocentric, consisting in the presence of the last band of the short arm of
      chromosome 17. This anomaly results from a 3:1 mal segregation of a balanced
      (13q17p) reciprocal maternal translocation leading to a trisomy 17pter. This is a
      previously undescribed chromosome anomaly.

PMID- 9150852
TI  - Cerebrovascular selectivity and vasospasmolytic action of the novel calcium
      antagonist (+/-)-(E)-1-(3-fluoro-6, 11-dihydrodibenz[b,e]oxepin-11-yl)-4-(3
      phenyl-2-propenyl)-piperazine dimaleate in isolated cerebral arteries of the
      rabbit and dog.
AB  - The cerebrovascular selectivity and vasospasmolytic action of AJ-3941 ((+/-)-(E)
      1-(3-fluoro-6, 11-dihydrodibenz[b,e]oxepin-11-yl)-4-(3-phenyl-2-propenyl)-p
      iperazine dimaleate. CAS 143110-70-7), a new calcium antagonist, were studied in
      isolated rabbit and dog arterial preparations. In rabbit arterial ring
      preparations, AJ-3941 dose-dependently inhibited the contractions of various
      arteries caused by high K(+)-depolarization (high K+) and prostaglandin F2 alpha
      (PG). The inhibitory potency of AJ-3941 varied in different arteries, in
      descending order as follows: high K+: basilar > coronary > femoral > renal >
      mesenteric artery, PG: basilar > coronary > > femoral and renal artery. The
      median inhibitory concentration (IC50) in the basilar artery was over 40 times
      lower than that in the mesenteric or femoral artery for which the weakest
      inhibition in the examined arteries was observed. This selective action of AJ
      3941 for cerebral artery was also observed in the frontal and middle cerebral
      arteries of dogs. The selectivity for the rabbit basilar artery was higher than
      those of flunarizine and nicardipine. Additionally, the contractile response of
      the rabbit basilar artery induced by phorbol 12,13-dibutyrate (PDBu), an
      activator of protein kinase C (PKC), was greater than those of the arteries
      examined such as the coronary, femoral and mesenteric arteries. The response in
      the basilar artery was greatly reduced in Ca(2+)-free medium, while this was not
      the case in other arteries. AJ-3941 as well as H-7, an inhibitor of PKC, potently
      inhibited PDBu-induced contractile response in the basilar artery in the
      presence, but not in the absence of Ca2+ in the medium, whereas the existing
      calcium antagonists, diltiazem and nicardipine, did not inhibit the contractile
      response in both conditions. These results suggest that the PKC-dependent system
      which is mediated by influx of extracellular Ca2+ profoundly contributes to the
      contraction of the cerebral artery and that the cerebroselective-vasodilating
      effect of AJ-3941 may depend, at least partly, on the inhibition of the PKC
      mediated contractile response. In rabbit basilar arteries, AJ-3941 caused a dose
      dependent inhibition of the contraction induced by various vasospasmogens, such
      as endothelin-1 (ET), arachidonic acid, 15-hydroperoxy-eicosatetraenoic acid and
      the thromboxane A2-mimetic U-46619. Furthermore, when isolated basilar arteries
      of the dog were perfused intraluminally with AJ-3941 at the concentration that
      inhibits high K(+)- or PG-induced contraction in the rabbit basilar artery, AJ
      3941 effectively antagonized the vasospasm induced by extraluminal application of
      PG or ET. However, when flunarizine, nicardipine, diltiazem or verapamil was used
      for intraluminal perfusion of the same preparations, none of these drugs exerted
      spasmolytic effect. These results indicate that AJ-3941 has cerebrovascular
      selective-vasospasmolytic action, and consequently is thought to be effective in
      cerebrovascular disorder such as vasospasm following subarachnoid hemorrhage.

PMID- 9150853
TI  - Quantitative determination of pentaerythrityl tetranitrate and its metabolites in
      human plasma by gas chromatography/mass spectrometry.
AB  - Up to now, there has been no data available on the pharmacokinetics of
      pentaerythrityl tetranitrate (PETN, CAS 78-11-5) and its metabolites,
      pentaerythrityl-trinitrate (PE-tri-N), pentaerythrityl-dinitrate (PE-di-N),
      pentaerythrityl-mononitrate (PE-mono-N) in human plasma. Therefore, in order to
      determine PETN and its metabolites in plasma sensitive and highly selective GC/MS
      methods had to be developed and validated. PETN and its metabolite PE-tri-N were
      validated in the concentration range 50 pg/ml to 10 ng/ml. Isosorbide dinitrate
      (ISDN) was used as the internal standard and the analytes were extracted with
      dichloromethane from the plasma. The mass spectrometric tests were carried out
      using chemical ionization in the negative mode (NlCl) with the application of
      ammonia as a reagent gas. The nitrate ion m/z 62 was determined in the analytes
      and internal standard. The accuracy of the mean of the quality control samples
      during the three days (between days) was between 100 and 110% (PETN), as well as
      90 and 106% (PE-tri-N). After an oral application of 100 mg PETN in a pilot
      study, unchanged PETN and PE-tri-N was measured in plasma. Both metabolites PE-di
      N and PE-mono-N were validated at the concentration range of 0.25 ng/ml to 25
      ng/ml plasma. After extraction, these analytes were derivatized with BSTFA (N,O
      bis[trimethylsilyl]trifluoro-acetamide). The applied internal standard was
      isosorbide-5-mononitrate (IS-5-MN). The mass spectrometric tests were carried out
      in the same manner as for PETN and PE-tri-N with chemical ionization in the NlCl
      mode. The detected masses were m/z 324 for PE-di-N, m/z 351 for PE-mono-N and m/z
      217 for IS-5-MN. The accuracy of the mean of the quality control samples during 5
      days were between 104 and 107% (PE-di-N) and 102 and 106% (PE-mono-N). The
      maximum concentration of these analytes in the subject samples were on the
      average all over 5 ng/ml plasma after the oral administration of 100 mg PETN.

PMID- 9150854
TI  - Effects of the alpha-/beta-blocking agent carvedilol on hepatic and systemic
      hemodynamics in patients with cirrhosis and portal hypertension.
AB  - To enhance the portal hypotensive effect of nonselective beta-blockers,
      combinations of vasoactive agents with different mechanisms should be considered.
      The effect of carvedilol (CAS 72956-09-3, Artist), and alpha-/beta-blocking
      agent, on hepatic and systemic hemodynamics in 10 patients with portal
      hypertension was evaluated. After administration of carvedilol, the hepatic
      venous pressure gradient (HVPG) decreased from 15.9 +/- 3.2 mmHg to 13.3 +/- 4.0
      mmHg (mean +/- SD) at 60 min (-15%) and to 12.9 +/- 3.0 mmHg at 90 min (-17%, p <
      0.05). However, only 5 patients showed a decrease of HVPG by more than 20% at 60
      or 90 min. The estimated hepatic blood flow (EHBF) was not significantly reduced.
      In contrast, heart rate (-8%, p < 0.05), mean arterial pressure (-10%, p < 0.01),
      and cardiac index (CI) (-8%, p < 0.05) were all reduced at 90 min, while total
      systemic vascular resistance was not altered. The reduction of HVPG was
      significantly correlated with the decrease of CI (r = 0.6415, p < 0.05). The
      portal hypotensive effect of carvedilol may mainly result from a reduction of CI.
      However, because of the greater reduction of HVPG than that of CI, other additive
      actions were suggested.

PMID- 9150855
TI  - Disposition and metabolism of the new oral antidiabetic drug troglitazone in
      rats, mice and dogs.
AB  - The pharmacokinetics of troglitazone (CAS 97322-87-7, CS-045), a new oral
      antidiabetic drug for the treatment of non-insulin-dependent diabetes mellitus
      (NIDDM), were investigated in rats, mice and dogs following oral and intravenous
      administration of 14C-labeled troglitazone at doses of 5 mg/kg. The absorption
      rates, calculated from the AUC ratios of total radioactivity after oral and
      intravenous administration, or from the biliary excretion rate after
      intraduodenal administration in rats were both as high as 75%. High uptake by the
      liver, one of the pharmacological target organs, was demonstrated in both rats
      and mice. Furthermore, in the KK mouse, an obese NIDDM model animal, the
      radioactivity was incorporated selectively as troglitazone itself to muscle, the
      peripheral target organ. Troglitazone reversibly bound to serum albumin with a
      high ratio (> 99%). Troglitazone was mostly metabolized to the conjugates:
      sulfate (M 1) and glucuronide (M 2). The oxidized metabolite, a quinone-type
      metabolite (M 3), was found to be further metabolized to the sulfate (U 2). The
      biliary excretion rates of these conjugates were high in each animal, and the
      occurrence of enterohepatic circulation of the conjugates was also suggested. Sex
      differences in pharmacokinetics were observed in rats; i.e. females showed a
      higher plasma concentration of troglitazone, and a lower concentration of M 1,
      than males, and they excreted the sex-related metabolite, a hydroxylated M 1 (U
      1), in the bile.

PMID- 9150856
TI  - Bioavailability of oral vitamins, minerals, and trace elements in perspective.
AB  - Bioavailability of orally administered vitamins, minerals, and trace elements is
      subject to a complex set of influences. Still, administrative regulation is
      necessary on how to quantify it. The most common approach to this problem is to
      determine the fraction of an oral dose that reaches the systemic circulation. For
      micronutrients, however, this approach has to consider the physiological plasma
      concentration as well as the mechanisms that regulate intestinal absorption and
      distribution of micronutrients between functional and storage compartments in
      response to the demand. The rate of exchange between these compartments has an
      impact on the delivery of such compounds into the plasma compartment as well as
      on the plasma clearance. Monitoring the area under the plasma concentration time
      curve after oral administration is an inadequate tool for bioavailability
      determination if there are substantial impacts of homeostatic mechanisms on the
      plasma concentration of a micronutrient. In nutritional science the term
      "bioavailability" encompasses the sum of impacts that may reduce or foster the
      metabolic utilisation of a nutrient. Bioavailability in this sense can be
      quantified by the rate by which deficiency symptoms are cured or by the weight
      gain during growth. both of these endpoints, again, are influenced by homeostatic
      mechanisms. To exemplify the scope of impacts on parameters that are commonly
      used to quantify the bioavailability of oral micronutrient preparations the basic
      traits of homeostatic regulation are summarised and compared for iron, magnesium,
      vitamin A, folic acid, and vitamin B12. The mechanisms that adapt absorption,
      distribution, and excretion of these five micronutrients to the demand differ to
      such an extent that no common approach can be derived to consider these impacts
      in bioavailability determination. In consequence, therefore, we recommend to
      define and regulate individual strategies for bioavailability testing for each
      micronutrient with regulated kinetics.

PMID- 9150857
TI  - Absorption and distribution of naproxen in rats orally treated with naproxen
      betainate sodium salt monohydrate. Comparison with naproxen.
AB  - The S-naproxen betainate sodium salt monohydrate (naproxen-betaNa, CAS 104124-26
      7, Aprenin) was synthesized to improve bioavailability and tolerability of
      naproxen. 24 albino rats were treated with naproxen-betaNa (84 mg/kg) and 24 with
      S-naproxen (naproxen) (50 mg/kg) by the oral route, the doses being equimolar.
      The animals were sacrificed and naproxen was assayed in timed plasma samples
      drawn off over a 24-h period and in tissues excised 1 h after administration.
      Peak concentrations of naproxen proved to be higher with naproxen-betaNa than
      with naproxen as such. The area under the curve of naproxen concentrations
      observed with the two administrations overlapped as did concentrations of the
      drug in the lungs, myocardium and liver. Naproxen concentrations in the gastric
      wall after naproxen-betaNa proved to be lower than after administration of
      naproxen as such, which allowed the authors to assume that naproxen-betaNa has a
      better gastric tolerability.

PMID- 9150858
TI  - Comparative bioavailability study on naproxen betainate sodium salt monohydrate
      and naproxen sodium salt in healthy volunteers.
AB  - The S-naproxen betainate sodium salt monohydrate (naproxen-betaNa, CAS 104124-26
      7, Aprenin, test drug), and the sodium salt of S-naproxen (reference), were
      administered to twelve healthy volunteers of both sexes according to a crossover
      design, in a single dose of one 575 mg capsule of test, containing 342 mg of S
      naproxen and two 275 mg tablets of reference, containing 502 mg of S-naproxen.
      Blood samples were drawn off over a 24-h period before (time 0) and after
      administration at foreseen time intervals. Naproxen was measured in plasma by a
      validated HPLC assay with UV detection which was able to detect 1 microgram/ml
      and proved to be linear in the range 1-100 micrograms/ml. The non-compartmental
      pharmacokinetic parameters obtained were statistically processed according to the
      EU guidance note on bioavailability and bioequivalence Cmax, AUC0-24h and AUC0
      infinity were normalized to the dose of 502 mg of naproxen and log-transformed
      before statistical analysis to assess bioequivalence. Dose-normalized values of
      plasma concentrations encountered with the two formulations proved to overlap,
      with the exception of the first sampling time which showed naproxen
      concentrations that were higher with test drug than with reference. The specific
      test for bioequivalence led to 90% confidence intervals within the 80-125% range
      with target pharmacokinetic parameters, whereas the time to peak (tmax) observed
      with the test and reference drugs did not differ to any statistically significant
      degree when analysed with Wilcoxon's non-parametric test. It is concluded that
      the test drug should be declared bioequivalent with the reference drug in terms
      of dose-normalized concentrations, despite the more rapid increase in plasma
      concentrations of naproxen observed at the first sampling time with test drug.

PMID- 9150859
TI  - Effect of an active metabolite of the antiallergic agent tazanolast on histamine
      release from rat mast cells.
AB  - WP-871 (3'-(1H-tetrazol-5-yl)oxanilic acid monohydrate, CAS 114607-46-4) is a
      monohydrate of a main active metabolite of tazanolast (butyl 3'-(1H-tetrazol-5
      yl) oxanilate, CAS 82989-25-1), an orally active antiallergic drug. WP-871
      inhibited dose-dependently compound 48/80-induced histamine release from rat
      peritoneal mast cells. In a similar dose range, WP-871 was effective in
      inhibiting compound 48/80-induced 45Ca uptake into mast cells from extracellular
      medium and compound 48/80-induced translocation of protein kinase C from the
      cytosol to the membrane fraction of mast cells. WP-871 also inhibited inositol
      trisphosphate production but did not exhibit a direct inhibitory effect on
      phospholipase C in mast cells. WP-871 caused no increase in cAMP content in mast
      cells. These results suggest that WP-871 may inhibit histamine release mainly by
      preventing the increase in intracellular Ca2+ concentration, which is a critical
      event in signal transduction leading to histamine release in mast cells.

PMID- 9150860
TI  - Experimental studies on the antitussive properties of the new xanthine derivative
      1H-purine-2,6-dione, 3,7-dihydro-3-methyl-7[(5-methyl-1,2,4-oxadiazol-3
      yl)methyl]. 1st communication: in vivo demonstration of the effects on animal
      models of cough and of mucociliary clearance.
AB  - CH-13584 (formerly: KHL-8425, 1H-purine-2,6-dione, 3,7-dihydro-3-methyl-7[(5
      methyl-1,2,4-oxadiazol-3-yl)methyl], CAS 115779-20-9) is a new xanthine
      derivative synthesized with the purpose to develop a highly safe compound against
      several pulmonary disorders, especially for the treatment of acute and chronic
      cough. CH-13584 showed acute and chronic antitussive activity on citric acid
      spray-evoked cough model in guinea-pig. CH-13584 was also effective on capsaicine
      spray and mechanical irritation-induced cough in guinea-pig and rabbit,
      respectively. The effectivity of CH-13584 on antitussive tests reached and in
      some cases even exceeded the effectivity of the reference compounds. The compound
      increased the mucociliary clearance at lower doses than bromhexine.

PMID- 9150861
TI  - Absorption of tretinoin in rats and rabbits following oral and dermal
      application.
AB  - To assess the teratogenic potential of Airol cream (0.05% tretinoin, CAS 302-79
      4), plasma concentrations were compared after repeated dermal applications of the
      maximum dose which could be applied reliably and after oral administration of the
      highest non-teratogenic dose. The test preparation was applied dermally in two
      equal portions to rats and rabbits at 2 g/animal/d (equivalent to a tretinoin
      dose of 3.7 mg/kg/d) and at 6 g/kg/d (equivalent to 3 mg tretinoin/kg/d),
      respectively. After a single oral administration of 2 mg/kg, Cmax and AUC for
      tretinoin in rat plasma were 285 +/- 14.6 ng/ml and 595 +/- 123 ng h/ml,
      respectively. Corresponding values for the rabbit were 78.4 +/- 16.9 ng/ml and
      126 +/- 25.4 ng h/ml. In both species, plasma concentrations of tretinoin after
      dermal application were consistently below the assay quantification limit (< 5
      ng/ml and < 2 ng/ml for rat and rabbit, respectively), despite marked irritation
      of the skin. Thus repeated topical application of the test preparation produced
      plasma concentration of tretinoin which were well below the plasma concentrations
      produced by a non-teratogenic oral dose of 2 mg/kg in the rat and rabbit.

PMID- 9150862
TI  - Synthesis and antibacterial activities of some 4,5-dihydro-1H-1,2,4-triazol-5
      ones.
AB  - Twenty-one new 1-methyl- and 1-ethyl-3,4-disubstituted-4,5-dihydro- 1H-1,2,4
      triazol-5-ones were synthesized and characterised by elemental analysis, 1H-NMR
      and IR spectra. These new and 16 recently reported derivatives of 4,5-dihydro-1H
      1,2,4-triazol-5-one ring were screened for their antibacterial activities.

PMID- 9150863
TI  - Synthesis and antimicrobial activity of 1-dialkylaminomethyl- 2-(p-substituted
      phenyl)-5-substituted benzimidazole derivatives.
AB  - 1-(Dialkylaminomethyl)-2-(p-substituted phenyl)-5-substituted benzimidazole
      derivatives 1 have been synthesized by reacting 2-phenylbenzimidazole derivatives
      with formaldehyde and a secondary amine. The derivatives of 2-phenylbenzimidazole
      were obtained by reacting the bisulfide addition product of substituted
      benzaldehydes with 4-substituted-o-phenylenediamines. Their structures were
      confirmed by microanalysis, IR and NMR spectral analysis. Antimicrobial activity
      of the compounds was investigated by the microdilution susceptibility test in
      Mueller-Hinton Broth and Sabouraud Dextrose Broth was used for the determination
      of antibacterial and antifungal activities. Test organisms: Staphylococcus aureus
      ATCC 29213 and Enterococcus faecalis ATCC 29212 as Gram-positive bacteria,
      Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853 as Gram
      negative bacteria, and Candida albicans, C. parapsilosis, C. stellatoidea as
      yeast-like fungi. Compounds 1a, 1b, 1c, 1e and 1i showed slight to moderate
      activity against all microorganisms. Compound 1g showed the highest activity. It
      was found more potent than streptomycin against Enterococcus faecalis and
      Pseudomonas aeruginosa.

PMID- 9150864
TI  - Aqueous humor penetration of topically applied ciprofloxacin, ofloxacin and
      tobramycin.
AB  - The purpose of this study was to determine the aqueous humor concentrations of
      topically applied ciprofloxacin (CAS 86393-32-0), ofloxacin (CAS 82419-36-1) and
      tobramycin (CAS 79645-27-5). Thirty patients undergoing cataract extraction or
      trabeculectomy were randomly divided into three groups and each of the group
      received either 0.3% ciprofloxacin, ofloxacin or tobramycin topical drops
      preoperatively. Eyedrops were instilled for six times at a frequency of one drop
      every 15 minutes, beginning 90 minutes before initiation of the surgery. At the
      time of surgery, 0.1 ml aqueous fluid was aspirated from the anterior chamber.
      Concentrations of the antimicrobial agents were determined using the microbroth
      dilution procedure outlined by the National Committee for Clinical Laboratory
      Standards. Escherichia coli (ATCC 25922) was used as a standard strain for
      determination of minimal inhibitory concentrations (MICs). The mean aqueous
      levels of ciprofloxacin and ofloxacin were found to be 0.092 +/- 0.077
      microgram/ml, 0.964 +/- 0.693 microgram/ml, respectively. Tobramycin did not
      reach the concentration that could be detected by applied method. CONCLUSION: The
      mean aqueous humor levels of ofloxacin and ciprofloxacin were more than the MICs
      levels for most of the ocular pathogens which may cause postoperative
      endophthalmitis.

PMID- 9150865
TI  - Electron-topological investigation of the structure-antitumor activity
      relationship of thiosemicarbazone derivatives.
AB  - In the frameworks of the electron-topological method (ETM) the structure
      antitumor activity relationship was investigated for a series of
      thiosemicarbazone derivatives. The series included 70 compounds. Conformational
      analysis and quantum-chemical calculations were carried out for each compound.
      The revealed activity feature showed a satisfactory description of the class of
      active compounds according to two different parameters P and alpha estimating the
      probabilities of the feature realization in the class of active compounds (they
      are equal to 0.94 and 0.86, correspondingly). The results of testing demonstrated
      the high ability of ETM in predicting the activity investigated.

PMID- 9150866
TI  - Conservation and diversity in the structure of translation initiation factor EIF3
      from humans and yeast.
AB  - Initiation factor eIF3 plays a central role in the initiation pathway,
      influencing ribosome association, ternary complex binding to 40S subunits, and
      mRNA binding, in part through an interaction with eIF4F. We are attempting to
      clone and sequence DNAs encoding the subunits of this complex factor. Mammalian
      eIF3 comprises 10 subunits; full-length human cDNAs have been cloned for eight of
      these, and partial clones are in hand for the remaining two. Yeast eIF3 comprises
      at least seven subunits, with six of the seven genes identified and sequenced.
      Comparison of eIF3 subunit sequences between human and yeast reveals an
      unexpectedly large diversity of structure. Surprisingly, comparisons with other
      sequences in the data base suggest that some of the eIF3 subunits may have
      functions apart from the eIF3 complex. Work is in progress to use the cloned DNAs
      as tools for elucidating the structure of eIF3 and its interactions with other
      initiation factors.

PMID- 9150867
TI  - The regulation of the protein kinase PKR by RNA.
AB  - A model is presented for the regulation of the double-stranded RNA (dsRNA)
      activated mammalian protein kinase PKR, which is involved in protein synthesis
      inhibition and the antiviral response in cells. A series of previous findings
      abut PKROs behavior are reviewed, including its effects on translation; the
      activation of its protein kinase activity; binding sites for PKR on RNA; PKROs
      protein domains, which include two double-stranded RNA binding motifs (dsRBMs);
      and the likelihood of PKR dimer formation. The model which emerges to account for
      many of these observations includes the suggestion that PKR dimers form which are
      stabilized and rearranged upon binding to dsRNA regions 60 bp or longer. The
      hypothesis includes protein conformational changes within each member of a PKR
      dimer bound to dsRNA which re-position an inhibitory polypeptide domain and thus
      allow kinase activation. Also considered are ways in which PKR interacts with
      imperfectly duplexed, highly structured RNA molecules.

PMID- 9150869
TI  - The ternary complex of aminoacylated tRNA and EF-Tu-GTP. Recognition of a bond
      and a fold.
AB  - The refined crystal structure of the ternary complex of yeast Phe-tRNAPhe,
      Thermus aquaticus elongation factor EF-Tu and the non-hydrolyzable GTP analog,
      GDPNP, reveals many details of the EF-Tu recognition of aminoacylated tRNA (aa
      tRNA). EF-Tu-GTP recognizes the aminoacyl bond and one side of the backbone fold
      of the acceptor helix and has a high affinity for all ordinary elongator aa-tRNAs
      by binding to this aa-tRNA motif. Yet, the binding of deacylated tRNA, initiator
      tRNA, and selenocysteine-specific tRNA (tRNASec) is effectively discriminated
      against. Subtle rearrangements of the binding pocket may occur to optimize the
      fit to any side chain of the aminoacyl group and interactions with EF-Tu
      stabilize the 3'-aminoacyl isomer of aa-tRNA. A general complementarity is
      observed in the location of the binding sites in tRNA for synthetases and for EF
      Tu. The complex formation is highly specific for the GTP-bound conformation of EF
      Tu, which can explain the effects of various mutants.

PMID- 9150868
TI  - A ribosomal protein from Thermus thermophilus is homologous to a general shock
      protein.
AB  - The gene encoding the ribosomal protein from Thermus thermophilus, TL5, which
      binds to the 5S rRNA, has been cloned and sequenced. The codon usage shows a
      clear preference for G/C rich codons that is characteristic for many genes in
      thermophilic bacteria. The deduced amino acid sequence consists of 206 residues.
      The sequence of TL5 shows a strong similarity to a general shock protein from
      Bacillus subtilis, named CTC. The protein CTC is homologous in its N-terminal
      part to the 5S rRNA binding protein, L25, from E coli. An alignment of the TL5,
      CTC and L25 sequences displays a number of residues that are totally conserved.
      No clear sequence similarity was found between TL5 and other proteins which are
      known to bind to 5S rRNA. The evolutionary relationship of a heat shock protein
      in mesophiles and a ribosomal protein in thermophilic bacteria as well as a
      possible role of TL5 in the ribosome are discussed.

PMID- 9150870
TI  - Functional specificity of amino acid at position 246 in the tRNA mimicry domain
      of bacterial release factor 2.
AB  - The termination of protein synthesis in bacteria requires codon-specific
      polypeptide release factors RF-1 (UAG/UAA specific) and RF-2 (UGA/UAA specific).
      We have proposed that release factors mimic tRNA and recognize the stop codon for
      polypeptide release (Nakamura et al (1996) Cell 87, 147-150). In contrast to the
      textbook view, genetic experiments have indicated that Escherichia coli RF-2
      terminates translation very weakly at UAA while Salmonella RF-2 decodes this
      signal efficiently. Moreover, an excess of E coli RF-2 was toxic to cells while
      an excess of Salmonella RF-2 was not. These two RF-2 proteins are identical
      except for 16 out of 365 amino acids. Fragment swap experiments and site-directed
      mutagenesis revealed that a residue at position 246 is solely responsible for
      these two phenotypes. Upon substituting Ala (equivalent to Salmonella RF-2) for
      Thr-246 of E coli RF-2, the protein acquired increased release activity for UAA
      as well as for UGA. These results led us to conclude that E coli RF-2 activity is
      potentially weak and that the amino acid at position 246 plays a crucial role,
      not for codon discrimination, but for stop codon recognition or polypeptide
      release, presumably constituting an essential moiety of tRNA mimicry or
      interacting with peptidyltransferase centers of the ribosome.

PMID- 9150871
TI  - The translational stop signal: codon with a context, or extended factor
      recognition element?
AB  - Wide ranging studies of the readthrough of translational stop codons within the
      last 25 years have suggested that the stop codon might be only part of the
      molecular signature for recognition of the termination signal. Such studies do
      not distinguish between effects on suppression and effects on termination, and so
      we have used a number of different approaches to deduce whether the stop signal
      is a codon with a context or an extended factor recognition element. A data base
      of natural termination sites from a wide range of organisms (148 organisms,
      approximately 40,000 sequences) shows a very marked bias in the bases surrounding
      the stop codon in the genes for all organisms examined, with the most dramatic
      bias in the base following the codon (+4). The nature of this base determines the
      efficiency of the stop signal in vivo, and in Escherichia coli this is reinforced
      by overexpressing the stimulatory factor, release factor 3. Strong signals,
      defined by their high relative rates of selecting the decoding release factors,
      are enhanced whereas weak signals respond relatively poorly. Site-directed cross
      linking from the +1, and bases up to +6 but not beyond make close contact with
      the bacterial release factor-2. The translational stop signal is deduced to be an
      extended factor recognition sequence with a core element, rather than simply a
      factor recognition triplet codon influenced by context.

PMID- 9150872
TI  - Influence of the last amino acid in the nascent peptide on EF-Tu during decoding.
AB  - The last two amino acids of the nascent peptide at the ribosomal P-site influence
      the efficiency of termination readthrough at the stop codon UGA (Mottagui-Tabar
      et al (1994) EMBO J 13, 249-257; Bjornsson et al (1996) EMBO J 15, 1696-1704).
      Here we analyze this effect on readthrough by wild type or a UGA suppressor form
      (Su9) of tRNA(Trp) by varying the codons at positions-1 and -2 at the 5' side of
      UGA. Strains with wild-type or mutant (ArBr) forms of elongation factor Tu (EF
      Tu) were analyzed (Vijgenboom et al (1985) EMBO J4, 1049-1052). The effect on
      readthrough by changing these-1 and -2 codons is different on the two forms of
      tRNA(Trp) and is also dependent on the structure of EF-Tu. Readthrough by the
      tRNA(Trp)-derived suppressor, but not wild-type tRNA(Trp), is sensitive to the
      van der Waals volume of the last amino acid in the nascent peptide. Together with
      mutant EF-Tu, both forms of tRNA(Trp) are sensitive. The data suggest that the C
      terminal amino acid in the nascent peptide is in a functional interaction with
      the EF-Tu ternary complex. This interaction is changed by mutation in tRNA(Trp)
      at position 24 or in EF-Tu at position 375. No indication of a changed
      interaction between the mutant EF-Tu and the penultimate amino acid could be
      found. Mutant forms of RF2 (Mikuni et al (1991) Biochimie 73, 1509-1516) and
      ribosomal proteins S4 and S12 (Faxen et al (1988) J Bacteriol 170, 3756-3760)
      were found not be altered in sensitivity to the last two amino acids in the
      nascent peptide.

PMID- 9150873
TI  - Dual functions of ribosome recycling factor in protein biosynthesis:
      disassembling the termination complex and preventing translational errors.
AB  - We summarize in this communication the data supporting the two functions of
      ribosome recycling factor (RRF, originally called ribosome releasing factor). The
      first described role involves the disassembly of the termination complex which
      consists of mRNA, tRNA and the ribosome bound to the mRNA at the termination
      codon. This process is catalyzed by two factors, elongation factor G (EF-G) and
      RRF. RRF stimulated protein synthesis as much as eight-fold in the in vitro
      lysozyme synthesis system, when ribosomes were limiting. In the absence of RRF,
      ribosomes remain mRNA-bound at the termination codon and translate downstream
      codons. In the in vitro system, the site of reinitiation is the triplet codon 3'
      to the termination codon. RRF is an essential protein for bacterial life.
      Temperature sensitive (ts) RRF mutants were isolated and in vivo translational
      reinitiation due to inactivation of ts RRF was demonstrated using the beta
      galactosidase reporter gene placed downstream from the termination codon. A
      second function of RRF involves preventing errors in translation. In
      polyphenylalanine synthesis programmed by polyuridylic acid, misincorporation of
      isoleucine, leucine or a mixture of amino acids was stimulated upto 17-fold when
      RRF was omitted from the in vitro system. RRF did not influence the large error
      (10-fold increase) induced by streptomycin. This means that RRF participates not
      only in the disassembly of the termination complex but also in peptide
      elongation. Extending this concept and its conventional role for releasing
      ribosomes from mRNA, involvement of RRF in the reinitiation in the 3A' system (a
      construct using S aureus protein A, a collaborative work with Dr Isaksson), in
      programmed frame shifting, in trans-translation with 10Sa RNA (collaborative work
      with Dr Muto), and in the reinitiation downstream from the ORF A of the IS 3
      (insertion sequence of a transposon, collaborative work with Dr Sekine) are
      discussed on the basis of preliminary data to be published elsewhere. Finally, we
      review the known RRF sequences from various organisms including eukaryotes and
      discuss the possible mechanism for disassembly of the eukaryotic termination
      complex.

PMID- 9150874
TI  - Structural model for the selenocysteine-specific elongation factor SelB.
AB  - A structural model was established for the N-terminal part of translation factor
      SelB which shares sequence similarity with EF-Tu, taking into account the
      coordinates of the EF-Tu 3D structure and the consensus of SelB sequences from
      four bacteria. The model showed that SelB is homologous in its N-terminal domains
      over all three domains of EF-Tu. The guanine nucleotide binding site and the
      residues involved in GTP hydrolysis are similar to those of EF-Tu, but with some
      subtle differences possibly responsible for the higher affinity of SelB for GTP
      compared to GDP. In accordance, the EF-Tu epitopes interacting with EF-Ts are
      lacking in SelB. Information on the formation of the selenocysteyl-binding pocket
      is presented. A phylogenetic comparison of the SelB domains homologous to EF-Tu
      with those from EF-Tu and initiation factor 2 indicated that SelB forms a
      separate class of translation factors.

PMID- 9150875
TI  - Structural organization of Escherichia coli tmRNA.
AB  - A secondary structure of Escherichia coli 10Sa RNA (tmRNA) recently proposed on
      the basis of a variety of chemical and enzymatic probing data combined with
      phylogenetic analysis (Felden et al, in press), indicates a highly folded
      structure. Several long-range interactions including pseudoknots are proposed
      based on comparative analysis of 10 tmRNA genes. Whereas most of the probing data
      support these predicted secondary structures, several atypical reactivities in
      specific domains of the molecule suggest structural dynamics, perhaps relating to
      the complex functions of the molecule as both tRNA and mRNA. The structure of
      tmRNA has three modular units; a tRNA-like domain, an mRNA-like domain and an
      intricate connecting unit probably responsible for correct orientation of the two
      functional parts of the molecule.

PMID- 9150876
TI  - Structure and function of 10Sa RNA: trans-translation system.
AB  - 10Sa RNA is a small stable bacterial RNA in which the 5'- and 3'-end sequences
      are folded into a tRNA-like structure. The RNA is aminoacylatable with alanine in
      vitro, and it interacts with 70S ribosomes in the cell. Recently, Escherichia
      coli 10Sa RNA has been shown to contain the sequence-encoding tag-peptides, which
      are found to attach to the C-termini of truncated peptides synthesized in vivo.
      We have found that the E coli 10Sa RNA stimulates incorporation of the tag
      specific amino acids into proteins depending on the poly(U)-directed poly
      phenylalanine synthesis in the in vitro translation system. Our finding supports
      the 'trans-translation' model proposed for the tag synthesis, in which alanyl
      10Sa RNA enters the ribosome when translation stops at the 3'-end of the
      truncated mRNA lacking a stop codon, and translation of the tag-peptide occurs by
      switching the template from mRNA to 10Sa RNA. In this unique reaction, 10Sa RNA
      acts both as a tRNA and as an mRNA.

PMID- 9150877
TI  - Codon reassignment in Candida species: an evolutionary conundrum.
AB  - A number of Candida species translate the standard leucine CUG codon as serine
      rather than as leucine. Such codon reassignment in nuclear-encoded mRNAs is
      unusual and raises a number of important questions about the origin of the
      genetic code and its continuing evolution. In particular we must establish how a
      codon can come to be reassigned without extinction of the species and what, if
      any, selective pressure drives such potentially catastrophic changes. Recent
      studies on the structure and identity of the novel CUG-decoding tRNA(Ser) from
      several different Candida species have begun to shed light on possible
      evolutionary mechanisms which could have facilitated such changes to the genetic
      code. These findings are reviewed here and a possible molecular mechanism
      proposed for how the standard leucine CUG codon could have become reassigned as a
      serine codon.

PMID- 9150878
TI  - Two nucleotides 5'-adjacent to the anticodon of rat cytoplasmic tRNA(Asp) are not
      edited.
AB  - Cytoplasmic tRNA(Asp) of rat liver was purified by the solid-phase hybridization
      method and its nucleotide sequence was analyzed by Donis-Keller's method. The
      results suggested that the two nucleotides next to the anticodon were identical
      to its gene sequence, a finding that is inconsistent with a previous report
      demonstrating by several methods that C32 and T33 on the tRNA(Asp) gene are post
      transcriptionally converted to U32 and C33, respectively (Beier et al (1992)
      Nucleic Acids Res 20, 2679-2683). Our results indicate that the tRNA hybridized
      to an oligonucleotide, designed on the basis of the tRNA(Asp) gene sequence,
      undergoes no editing and possesses C32 and U33 as predicted from the DNA
      sequence. Analysis of cDNA synthesized from the purified tRNA(Asp) by the RT-PCR
      method supported the finding that RNA editing is not involved in the maturation
      process of rat cytoplasmic tRNA(Asp).

PMID- 9150879
TI  - Nonsense suppression in mammalian cells.
AB  - Mammalian cells contain suppressor tRNAs that can translate nonsense codons such
      as UAG and UGA localized at a specific site of natural mRNAs. For translation of
      these nonsense codons, a specific secondary or tertiary structure of mRNAs
      located in the region surrounding the translatable nonsense codon is required. In
      mammalian cells, transcriptional expression of the tRNA gene encoding UAG
      suppressor glutamine tRNA is repressed by the binding of a nuclear protein to a
      specific site in the 5'-flanking region of the gene. Based on these findings, we
      discuss the translational regulation of nonsense codons in mammalian mRNAs.

PMID- 9150880
TI  - Some novel transcription attenuation mechanisms used by bacteria.
AB  - A variety of transcription attenuation mechanisms are used by bacteria to
      regulate gene and operon expression. This review summarizes previous and current
      studies designed to elucidate the features of the specific attenuation mechanisms
      that regulate expression of the tryptophanase (tna) operon of Escherichia coli
      and the tryptophan (trp) operon of Bacillus subtilis. Initiation of transcription
      in the tna operon is regulated by catabolite repression. Once initiated,
      transcription is regulated by tryptophan-induced inhibition of Rho-mediated
      transcription termination in the leader region of the operon. An operon-encoded
      leader peptide, TnaC, containing a crucial tryptophan residue, plays an essential
      role in induction. This peptide appears to act in cis on the ribosome translating
      tnaC to inhibit its release at the tnaC stop codon. The stalled ribosome would
      block Rho's access to the tna transcript, thereby preventing termination.
      Transcription of the trp operon of B subtilis is regulated by an attenuation
      mechanism that responds to a tryptophan-activated eleven subunit RNA-binding
      regulatory protein, called TRAP. Activated TRAP binds to repeated GAG sequences
      in the leader segment of the trp operon transcript, disrupting an RNA
      antiterminator and promoting formation of a terminator. Activated TRAP also
      regulates translation of trpG in the folate operon by binding to repeat GAG
      sequences surrounding the trpG ribosome binding site. A temperature sensitive
      tryptophanyl-tRNA synthetase (trpS) mutant was previously observed to overexpress
      the trp operon and trpG, when grown at elevated temperatures in the presence of
      tryptophan. We have found that the trpS defect increases trp operon and trpG
      expression by interfering with TRAP's ability to act. We suggest that either
      accumulation of uncharged tRNA(Trp) or overproduction of a TRAP-binding
      transcript reduces the level of functional TRAP in the trpS mutant.

PMID- 9150882
TI  - Differential contributions of two elements of rho-independent terminator to
      transcription termination and mRNA stabilization.
AB  - The hallmark features of rho-independent transcription terminators are a G(+)C
      rich dyad symmetry sequence followed by a run of T residues on a sense strand.
      Both of these structural elements are required for efficient transcription
      termination. Besides its primary function, rho-independent terminators are also
      known to enhance expression of an upstream gene by stabilizing RNA in a few
      cases. The Escherichia coli crp gene encoding cAMP receptor protein (CRP)
      contains a typical rho-independent terminator. To gain further insight into the
      roles of the G(+)C-rich dyad symmetry sequence and the poly(T) tract both in
      transcription termination and mRNA stabilization, we constructed a series of
      variant crp terminators and analyzed their abilities regarding these two
      functions. Disruption of the G(+)C-rich dyad symmetry sequence almost completely
      eliminated terminator activity while disruption of the poly(T) tract reduced
      terminator activity significantly but not completely. Thus, the contribution of
      the G(+)C-rich dyad symmetry sequence to transcription termination is larger than
      that of the poly(T) tract. Disruption of the G(+)C-rich dyad symmetry region
      reduced expression of the upstream crp gene by accelerating the rate of mRNA
      degradation. However, disruption of the poly(T) sequence had no effect on the
      stability of the crp mRNA, indicating that the poly(T) tract plays no role in
      mRNA stabilization. When the crp terminator was replaced by terminators derived
      from other genes, the fusion genes expressed the crp mRNA at the same level as
      did the native crp gene, suggesting that the mRNA stabilization effect is
      probably a general nature of rho-independent terminators.

PMID- 9150881
TI  - Structure and regulation of the Salmonella typhimurium rnc-era-recO operon.
AB  - The Escherichia coli rnc-era-recO operon encodes ribonuclease III (RNase III; a
      dsRNA endonuclease involved in rRNA and mRNA processing and decay), Era (an
      essential G-protein of unknown functions and RecO (involved in the RecF
      homologous recombination pathway). Expression of the rnc and era genes is
      negatively autoregulated: RNase III cleaves the rncO 'operator' in the
      untranslated leader, destabilizing the operon mRNA. As part of a larger effort to
      understand RNase III and Era structure and function, we characterized rnc operon
      structure, function and regulation in the closely related bacterium Salmonella
      typhimurium. Construction of a S typhimurium strain conditionally defective for
      RNase III and Era expression showed that Era is essential for cell growth. This
      mutant strain also enabled selection of recombinant clones containing the intact
      S typhimurium rnc-era-recO operon, whose nucleotide sequence, predicted protein
      sequence, and predicted rncO RNA secondary structure were all highly conserved
      with those of E coli. Furthermore, genetic and biochemical analysis revealed that
      S typhimurium rnc gene expression is negatively autoregulated by a mechanism very
      similar or identical to that in E coli, and that the cleavage specificities of
      RNase IIIs.t. and RNase IIIE.c. are indistinguishable with regard to rncO
      cleavage and S typhimurium 23S rRNA fragmentation in vivo.

PMID- 9150883
TI  - Cytoplasmic mRNA for human triosephosphate isomerase is immune to nonsense
      mediated decay despite forming polysomes.
AB  - Nonsense codons between position 14 within the first exon and position 193 within
      the penultimate exon of the human gene for triosephosphate isomerase reduce mRNA
      abundance to 25% of normal. The reduction in abundance is due to the decay of
      newly synthesized mRNA that copurifies with nuclei. TPI mRNA that copurifies with
      cytoplasm is immune to decay. We show here that immunity is not due to the
      failure of nonsense-containing mRNA to form polysomes. This finding indicates
      that cytoplasmic mRNA, in contrast to nucleus-associated mRNA, may have lost one
      or more factors that are required for nonsense-mediated decay or gained one or
      more factors that confer immunity to nonsense-mediated decay.

PMID- 9150884
TI  - mRNA decapping activities and their biological roles.
AB  - The 5' cap structure of eukaryotic mRNAs is significant for a variety of cellular
      events and also serves to protect mRNAs from premature degradation. Analysis of
      mRNA decay in Saccharomyces cerevisiae has shown that removal of the 5' cap
      structure is a key step in the turnover of many yeast mRNAs, and that this
      decapping is carried out by Dcp1p. In addition to the yeast decapping enzyme,
      other activities that can cleave the 5' cap structure have been described. These
      include two mammalian enzymes and two viral activities that cleave cellular mRNA
      cap structures as part of their life cycle. Here we review these various
      decapping activities and discuss their biological roles.

PMID- 9150885
TI  - Site-specific substitution of inosine at the terminal positions of a pre-mRNA
      intron: implications for the configuration of the terminal base interaction.
AB  - Genetic evidence in yeast has revealed that a non-Watson-Crick base-pairing
      interaction between terminal guanosine residues of the intron is required for the
      second step of pre-mRNA splicing. To explore the likely configuration of the
      interaction between the terminal guanosines of the intron, inosine was uniformly
      incorporated into an adenovirus pre-mRNA substrate (Ade) to replace guanosine
      residues. Splicing of the inosine-containing Ade pre-mRNA was completely
      inhibited. Psoralen cross-linking reveals that the association of U1 and U2
      snRNPs with the intron was impaired. To eliminate the deleterious effects caused
      by complete inosine replacement, guanosine residues at the splice site(s) of the
      Ade pre-mRNA were substituted by inosine. Such pre-mRNA substrates were obtained
      by ligation of two or three RNA fragments; the 3' piece was primed with inosine
      or mono-phosphate inosine. Splicing of the Ade pre-mRNA containing an inosine
      residue at the 5' or the 3' splice site, or at both sites proceeds normally.
      Thus, the functions of the terminal guanosine residues of the intron in splicing
      can be replaced by inosine. This result supports the previous notion that an N1
      carbonyl symmetric interaction likely occurs between the intron terminal residues
      during pre-mRNA splicing.

PMID- 9150886
TI  - In vitro catalytic activities of DNA/RNA chimeric hammerhead ribozymes against
      AML1-MTG8 mRNA, a fused gene transcript in acute myeloid leukemia with t(8;21).
AB  - In order to design the best construct for therapeutic hammerhead ribozymes
      against AML1-MTG8, the t(8;21)-associated fusion mRNA of acute myeloid leukemia,
      we synthesized DNA/RNA chimeric ribozymes directed to the area adjacent to the
      fusion point between AML1 and MTG8. Catalytic efficiency and fusion gene
      specificity of ribozymes were examined by kinetic studies of the cleavage
      reactions of AML1-MTG8, AML1, and MTG8 RNAs transcribed in vitro. Ribozyme 2
      (Rz2) specifically cleaved AML1-MTG8 RNA at three nucleotides downstream of the
      fusion junction with high efficiency. The highest cleavage efficiency was
      achieved by Rz4.3, which targeted non-contiguous sequences and cleaved at 19
      nucleotides downstream of the fusion junction. Rz4.3 also cleaved MTG8 RNA but
      the cleavage efficiency was three orders of magnitude lower than that for AML1
      MTG8 RNA. Therefore, Rz4.3 and Rz2 are the proper ribozymes for in vivo
      application to modulate gene expression of the AML1-MTG8.

PMID- 9150887
TI  - A role for Rev in the association of HIV-1 gag mRNA with cytoskeletal beta-actin
      and viral protein expression.
AB  - Human immunodeficiency virus type-1 (HIV-1) Rev acts by inducing the specific
      nucleocytoplasmic transport of a class of incompletely spliced RNAs that encodes
      the viral structural proteins. The transfection of HeLa cells with a rev
      defective HIV-1 expression plasmid, however, resulted in the export of
      overexpressed, intron-containing species of viral RNAs, possibly through a
      default process of nuclear retention. Thus, this system enabled us to directly
      compare Rev+ and Rev+ cells as to the usage of RRE-containing mRNAs by the
      cellular translational machinery. Biochemical examination of the transfected
      cells revealed that although significant levels of gag and env mRNAs were
      detected in both the presence and absence of Rev, efficient production of viral
      proteins was strictly dependent on the presence of Rev. A fluorescence in situ
      hybridisation assay confirmed these findings and provided further evidence that
      even in the presence of Rev, not all of the viral mRNA was equally translated. At
      the early phase of RNA export in Rev+ cells, gag mRNA was observed throughout
      both the cytoplasm and nucleoplasm as uniform fine stippling. In addition, the
      mRNA formed clusters mainly in the perinuclear region, which were not observed in
      Rev+ cells. In the presence of Rev, expression of the gag protein was limited to
      these perinuclear sites where the mRNA accumulated. Subsequent staining of the
      cytoskeletal proteins demonstrated that in Rev+ cells gag mRNA is colocalized
      with beta-actin in the sites where the RNA formed clusters. In the absence of
      Rev, in contrast, the gag mRNA failed to associate with the cytoskeletal
      proteins. These results suggest that in addition to promoting the emergence of
      intron-containing RNA from the nucleus, Rev plays an important role in the
      compartmentation of translation by directing RRE-containing mRNAs to the beta
      actin to form the perinuclear clusters at which the synthesis of viral structural
      proteins begins.

PMID- 9150888
TI  - The post-transcriptional regulator Rev of HIV: implications for its interaction
      with the nucleolar protein B23.
AB  - Human T cell leukemia virus type 1 (HTLV-1) and human immunodeficiency virus type
      1 (HIV-1) belong to the complex retrovirus whose replication is controlled by
      trans-acting proteins. HIV-1 encodes several regulatory proteins, including two
      essential trans-activations for viral replication, Rev and Tat. Both Rev and Tat
      have a nucleolar targeting signal and are actually located predominantly in the
      nucleoli. Within the nucleoli, Rev is localized to the combined regions of the
      dense fibrillar (DFC) and the granular (GC) components. Tat does not colocalize
      precisely with any nucleolar component tested, but partly overlaps regions of the
      DFC and the GC. Regions of both Rev and Tat are overlapped by the distribution of
      the major nucleolar protein B23. Overexpression of Rev causes nucleolar
      ballooning and general structural deformity with aberrant accumulation of rRNAs,
      whereas Tat does not have that effect. B23 is markedly accumulated in those
      nucleoli deformed by Rev. Components of the nucleolar DFC, GC, and fibrillar
      center domains are not accumulated but dispersed in a few small spots or larger
      patches within the enlarged nucleoli. Cytophotometric DNA determinations revealed
      that transient expression of Rev results in accumulation of G2, prophase, and
      mitotic cells which have failed cytokinesis, suggesting that Rev is capable of
      preventing or slowing the progression through mitosis. Tat, in contrast, does not
      affect the cell cycle. We speculate, based on these results, that Rev represses
      cell growth inhibiting the transport of ribosomal proteins and preribosomal
      particles across the nuclear envelope and affecting the cell cycle, both of which
      may be related to the proposed functions of B23.

PMID- 9150889
TI  - Structural and functional evidence that initiation and elongation of HIV-1
      reverse transcription are distinct processes.
AB  - Retroviral reverse transcription starts with the extension of a cellular tRNA
      primer bound near the 5' end of the viral genomic RNA at a site called the primer
      binding site (PBS). Formation of the HIV-1 initiation complex between tRNA3(Lys),
      viral RNA and reverse transcriptase probably occurs during encapsidation of these
      components. tRNA3(Lys) is thought to be selectively packaged by interaction with
      the reverse transcriptase domain of the Pr160Gag-Pol precursor protein, then
      annealed to the PBS of viral RNA with the help of the nucleocapsid protein.
      tRNA3(Lys) and HIV-1 viral RNA form a highly-structured complex, with extended
      interactions between the two molecules. Two different modes of reverse
      transcription have been distinguished: initiation, a tRNA3(Lys)-specific and
      distributive mode of polymerization corresponding to the addition of the first
      five nucleotides, followed by elongation, a non-specific and processive mode of
      DNA synthesis. These two modes are reminiscent of the initiation and elongation
      processes previously observed with DNA-dependent RNA polymerases.

PMID- 9150890
TI  - A multi-functional enzyme with RNA polymerase and RNase activities: molecular
      anatomy of influenza virus RNA polymerase.
AB  - Influenza virus-associated RNA polymerase is composed of one molecule each of
      three viral P proteins and carries the complete activity of capped RNA-primed
      vRNA-directed transcription. The RNA polymerase holoenzyme also carries capped
      RNA endonuclease to generate capped oligonucleotide primers for transcription and
      3'-to-5' exonuclease to remove erroneously polymerized nucleotides at nascent RNA
      3' termini prior to the addition of correct substrates. PB1 is the core subunit
      for not only RNA synthesis but also the assembly of PB2 and PA into the
      holoenzyme complex, while PB2 plays a key role in capped RNA cleavage. The
      transcriptase is converted into the RNA replicase with the full activity of
      replication, ie vRNA-directed cRNA synthesis and cRNA-directed vRNA synthesis,
      after interaction with an as yet unidentified host factor(s).

PMID- 9150891
TI  - Identification of host factors that regulate the influenza virus RNA polymerase
      activity.
AB  - Transcription and replication of the influenza virus RNA genome take place in the
      nuclei of infected cells. Ribonucleoprotein (RNP) complexes consisting of viral
      RNA, RNA polymerase, and nucleocapsid protein (NP) are proven to be the catalytic
      unit for RNA synthesis, while it has been indicated that the viral RNA polymerase
      activity is modulated by host-derived nuclear factors. Here we have identified
      such host factors present in nuclear extracts prepared from uninfected HeLa cells
      with biochemical complementation assays using the in vitro RNA synthesis system.
      The stimulatory activity was not absorbed to phosphocellulose but was tightly
      bound to Q-Sepharose. The eluate recovered from Q-Sepharose was able to stimulate
      the RNA synthesis catalyzed by both RNP complexes and purified RNA polymerase and
      NP. The stimulatory activity was further separated into two distinct fractions,
      designated RAF-1 (RNA polymerase activating factor-1) and RAF-2 fractions,
      through phenyl-Sepharose column chromatography. When these fractions were
      fractionated through a gel filtration column, RAF-1 and RAF-2 activities were
      recovered in fractions corresponding to the molecular mass of 350 kDa and 60 kDa,
      respectively. Furthermore, the RAF-2 fraction was shown to contain an inhibitory
      activity, tentatively designated RIF-1 (RNA polymerase inhibitory factor-1). RIF
      1 sedimented as fast as bovine serum albumin in glycerol density gradient
      centrifugation. Roles of these host factors are discussed in the context of viral
      RNA transcription and replication.

PMID- 9150892
TI  - Mechanisms of primer RNA synthesis and D-loop/R-loop-dependent DNA replication in
      Escherichia coli.
AB  - In DNA replication, DNA chains are generally initiated from small pieces of
      ribonucleotides attached to DNA templates. These 'primers' are synthesized by
      various enzymatic mechanisms in Escherichia coli. Studies on primer RNA synthesis
      on single-stranded DNA templates containing specific 'priming signals' revealed
      the presence of two distinct modes, ie immobile and mobile priming. The former
      includes primer RNA synthesis by primase encoded by dnaG and by RNA polymerase
      containing a sigma 70 subunit. Priming is initiated at a specific site in
      immobile priming. Novel immobile priming signals were identified from various
      plasmid replicons, some of which function in initiation of the leading strand
      synthesis. The latter, on the other hands involves a protein complex, primosome,
      which contains DnaB, the replicative helicase for E coli chromosomal replication.
      Utilizing the energy fueled by ATP hydrolysis of DnaB protein, primosomes are
      able to translocate on a template DNA and primase synthesizes primer RNAs at
      multiple sites. Two distinct primosomes, DnaA-dependent and PriA-dependent, have
      been identified, which are differentially utilized for E coli chromosomal
      replication. Whereas DnaA-dependent primosome supports normal chromosomal
      replication from oriC, the PriA-dependent primosome functions in oriC-independent
      chromosomal replication observed in DNA-damaged cells or cells lacking RNaseH
      activity. In oriC-independent replication, PriA protein may recognize the D- or R
      loop structure, respectively, to initiate assembly of a primosome which mediates
      primer RNA synthesis and replication fork progression.

PMID- 9150894
TI  - Some morphological features of a visual thalamic nucleus in a reptile:
      observations on nucleus rotundus in Caiman crocodilus.
AB  - The morphology of nucleus rotundus, a visual thalamic nucleus, was investigated
      in one species of reptiles. Caiman crocodilus, using Nisst stained material in
      transverse, sagittal, and horizontal planes. The topographical location of
      nucleus rotundus and its relationship to surrounding thalamic nuclear groups are
      described. Nucleus rotundus in Caiman can be subdivided into three areas: (1) an
      outer shell; (2) an inner core; and (3) a cell poor zone located between the
      shell and core. Most rotundal core neurons were round, fusiform, triangular, pear
      shaped, or elliptical. Core neurons were not distributed evenly throughout the
      nucleus but, in many instances, were arranged in clusters composed of two to ten
      neurons. Quantitative measurements of area, perimeter, and eccentricity (greatest
      width/greatest length), which served as an index of cell roundness, were made on
      rotundal core neuron profiles in transverse, sagittal, and horizontal planes of
      section. Qualitative and quantitative observations were not appreciably different
      regardless of the plane of orientation. Both qualitative and quantitative data
      suggest that relay cells located in the core of nucleus rotundus are not a
      homogeneous population of neurons but comprise several subtypes.

PMID- 9150893
TI  - Prokaryotic and eukaryotic translation factors. Ad Hoc Nomenclature Subcommittee
      Report.

PMID- 9150895
TI  - Postembryonic changes in the structure of the olfactory bulb of the chinook
      salmon (Oncorhynchus tshawytscha) across its life history.
AB  - Juvenile chinook salmon (Oncorhynchus tshawytscha) memorize odors characteristic
      of their natal stream, then use these imprinted olfactory cues to return to that
      same stream years later as sexually mature adults. In a preliminary effort to
      identify neuroanatomical changes in the salmon olfactory system that may underlie
      these behavioral capabilities, the structure of the olfactory bulb (OB) was
      studied at three developmental periods across the life history: in early juvenile
      development (0.1-4 months of age), in late juvenile development (11-16 months),
      and as spawning adults (48 months). Using antibodies that selectively label
      primary olfactory afferents (anti-keyhole limpet hemocyanin), combined with a
      thionin counterstain, the telencephalon (TEL), OB, and two of the bulb's laminar
      components, the olfactory nerve-glomerular layer (ONL-GL) and inner cell layer
      (ICL), could be easily identified. Laminar organization and relative volume (i.e.
      percent of OB comprised by ONL-GL or ICL) were then compared across groups, and
      absolute volumes of the OB, ONL-GL, and ICL were compared to that of the TEL at
      each stage. Three age-related processes were observed across the life history.
      First, a rapid increase in organizational and structural maturity of the OB was
      found to be confined to early juvenile life. Second, an increase in OB, ONL-GL,
      and ICL volume, relative to TEL volume, was found to occur across the entire life
      history. Lastly, the composition of the OB itself changed, in that an increase in
      the relative volume of the ONL-GL, and a decrease in that of the ICL, were
      observed across the life history. Taken together, these results indicate that the
      OB of young salmon matures dramatically while the fish is still in the freshwater
      phase of its life history. Then, during migration to the ocean and growth to the
      adult stage, the volume of the OB, relative to that of the telencephalon, and the
      relative volume of the input layer of the bulb, both undergo a marked, continuous
      increase. These changes in the structure, and presumably the function, of the
      olfactory bulb of salmon may be important in the behavioral phenomena of
      olfactory imprinting as juveniles and homing as adults.

PMID- 9150896
TI  - Autoradiographic localization of arginine vasopressin binding sites in the brain
      of adult and developing Brazilian opossums.
AB  - We are utilizing the Brazilian short-tailed opossum, Monodelphis domestica, to
      study the development of the vasopressinergic system. Earlier studies
      demonstrated that arginine vasopressin-like immunoreactivity was present very
      early in the Brazilian opossum brain, suggesting a role for vasopressin in the
      developing central nervous system of mammals. In this study, we have utilized
      [3H]arginine vasopressin autoradiography to describe the distribution of arginine
      vasopressin binding sites in adult and developing Brazilian opossum brains. In
      general, arginine vasopressin binding patterns in adult opossum brains resembled
      those of other species. However, we found very few labelled areas in neonatal
      Brazilian opossum brains. At birth, only the ventral tegmental area and the
      nucleus of the solitary tract were labelled. Binding was not evident in the
      forebrain until 25 days of postnatal age. The anterior pituitary was heavily
      labelled from birth onward, but binding in the brain itself remained at low
      levels until 35 days postnatal. Heavy binding was observed in only a few areas of
      the brain in adults, including the dorsal part of the lateral septal nucleus, the
      suprachiasmatic nucleus, the dorsal and median raphe, the nucleus of the solitary
      tract, and the caudal part of the spinal trigeminal nucleus. Surprisingly,
      arginine vasopressin binding sites in the Brazilian opossum appeared much later
      than arginine vasopressin immunoreactivity and, in many cases, after neurogenesis
      was complete. These findings suggest that the arginine vasopressin binding sites
      are not playing a developmental role in opossums, although the peptide is present
      at an early age.

PMID- 9150897
TI  - Cyto- and myeloarchitectonic organisation of the spinal cord of an echidna
      (Tachyglossus aculeatus).
AB  - We have studied the cyto- and myeloarchitectural organisation of the spinal cord
      of an echidna (Tachyglossus aculeatus) with the aid of Nisst staining, darkfield
      examination and p-phenylenediamine staining. We have also examined the
      distribution of unmyelinated afferents by labelling with a peroxidase-conjugated
      lectin derived from Griffonia simplicifolia (B1 isolectin). The cytoarchitectural
      features characterising the laminar organisation of the spinal cord in eutherian
      mammals were broadly applicable to the spinal cord of this monotreme. In
      addition, we identified a distinct group of large neurons in the ventral part of
      lamina X, extending into the ventral funiculus, that we have called the median
      nuclear group. We were unable to identify a central cervical nucleus in this
      echidna on the basis of cytoarchitectural criteria, although all other spinal
      cord nuclei found in eutherians could be found in this monotreme. Lectin
      labelling with the Griffonia simplicifolia isolectin B4 revealed a subpopulation
      of dorsal root ganglion cells similar to those labelled in Eutheria. In this
      echidna, labelling of unmyelinated fibres was found in Lissauer's zone and
      laminae I and II, as seen in rats (Rattus norvegicus); there were also deeper
      patches extending into laminae III to V and what appeared to be commissural axons
      approaching the dorsal grey commissure, which have not been seen in Eutheria.
      Fibre calibre in the dorsal and ventral roots of this echidna was similar to that
      reported in Eutheria, suggesting similar proportion of afferent fibre classes and
      alpha and gamma motoneurons. In the echidna, mean diameter of myelinated dorsal
      root axons was 4.65 microns at T1 and 5.22 microns at L3, with a clear bimodal
      distribution in the L3 dorsal root showing distinct groups at 1 to 5 microns and
      6 to 12 microns. These made up approximately 45 and 55% of the total myelinated
      axon population, respectively. Myelinated fibres in the ventral root at L3 showed
      two major peaks in distribution. These were at 1 to 4 microns (approximately 32%
      of the total myelinated fibre population) and at 7 to 14 microns (approximately
      58% of the total myelinated fibre population). The cross-sectional area of the
      dorsal columns of this monotreme was comparable to that of a eutherian mammal of
      similar body weight, and myelinated axon calibre was similar to that seen in the
      domestic cat. Our findings indicated that spinal cord cytoarchitectural
      organisation is highly conserved across class Mammalia, although the lectin
      labelling findings suggested that termination of unmyelinated afferents in
      echidnas may differ from that found in Eutheria. The dorsal column system appears
      to be as anatomically well developed in this monotreme as in those eutherian
      mammals considered to have a pronounced discriminative tactile sense.

PMID- 9150898
TI  - Mitoxantrone dose augmentation utilizing filgrastim support in combination with
      fixed-dose 5-fluorouracil and leucovorin in women with metastatic breast cancer.
AB  - Based on reports of substantial antitumor efficacy of the combination of
      mitoxantrone (DHAD), 5-fluorouracil (FU) and leucovorin (LV), a clinical trial
      was performed to attempt augmentation of the dose of DHAD with filgrastim
      support. The doses and schedules, all intravenous, were DHAD (total dose divided
      over days 1 and 2), level I, 16 mg/m2; II, 20 mg/m2; III, 24 mg/m2; IV, 32 mg/m2;
      and LV, 300 mg, followed by FU, 350 mg/m2, on days 1-3. Filgrastim was given at 5
      micrograms/kg/day subcutaneously on days 4-13. The planned cycle length was 21
      days. Three or 4 patients were to be entered at each dose level and the maximum
      tolerated dose (MTD) was defined as the dose immediately below that which
      resulted in 2 patients with dose-limiting toxicity (DLT) in cycle 1. Once an
      apparent MTD was identified, an additional 6 patients were to be entered. Twenty
      patients (pts) were entered: level I: 3 pts; II: 3 pts; III: 10 pts: IV: 4 pts.
      The major toxicity was found to be cumulative thrombocytopenia with platelet
      counts < or = 20,000/microL occurring after cycle 1 at all levels beyond level I
      and five pts (25%) were removed from treatment solely because of platelet
      toxicity. Additional serious toxicities included grade 4 stomatitis in one
      patient (level IV) and cardiac toxicity in 2 patients with prior doxorubicin
      exposure. Ten pts had measurable and 8 had evaluable disease, and in 17 pts
      assessed, 5 (29%) achieved an objective response. The response rates in this
      study are lower than reported in the literature for the combination of DHAD, 5FU,
      LV and this may be related to the fact that only 40% of the patients were removed
      from protocol treatment because of disease progression. On the basis of limited
      DHAD-dose augmentation, toxicities observed, and modest response rate, the
      filgrastim-supported DHAD, 5FU, LV regimen as utilized in this study cannot be
      recommended for further development for treatment of women with metastatic breast
      cancer.

PMID- 9150900
TI  - Serum concentration of tumor necrosis factor in patients with breast cancer.
AB  - BACKGROUND: The outcome of breast cancer is usually determined by multiple
      factors. Serum tumor necrosis factor alpha concentration has been found to be
      increased in the circulation of patients with malignancy. This study was designed
      with the aim to investigate any correlation between the serum tumor necrosis
      factor alpha and the clinicopathological features and furthermore evaluate the
      prognostic significance of serum tumor necrosis factor alpha concentration in
      breast cancer. METHODS: Forty consecutive patients with invasive breast cancer
      undergoing modified radical mastectomy were prospectively included and evaluated.
      Venous blood samples were collected before the surgery. Sera were obtained by
      centrifugation, and stored at -70 degrees C until assayed. The control group
      consisted 30 healthy, age-matched subjects. Serum concentrations of tumor
      necrosis factor alpha were measured by the quantitative sandwich enzyme
      immunoassay technique. The data on tumor size, age, estrogen receptor status,
      lymph node status and TNM staging were reviewed and recorded. RESULTS: The mean
      value of serum tumor necrosis factor alpha in patients with invasive breast
      cancer was 1.47 +/- 0.58 pg/ml and that of the control group was 0.98 +/- 0.37
      pg/ml, and the difference was significant (P < 0.01). With univariable analysis,
      patients with maximum tumor size of 5 cm or larger (P = 0.03), more advanced TNM
      staging (P < 0.01); and more advanced lymph node status (P < 0.01) were shown to
      have significantly higher serum concentrations of tumor necrosis factor alpha.
      However, with multivariable analysis, TNM staging appeared as the only
      independent factor (P < 0.01) predicting the significant, higher serum
      concentrations of tumor necrosis factor alpha. CONCLUSION: Preoperative
      evaluation of serum tumor necrosis factor alpha concentrations may be a valuable
      parameter for reflecting the severity of staging for invasive breast cancer.

PMID- 9150899
TI  - Feasibility of obtaining breast epithelial cells from healthy women for studies
      of cellular proliferation.
AB  - Increased dietary fat intake and rate of breast epithelial cell proliferation
      have each been associated with the development of breast cancer. The goal of this
      study was to measure the effect of a low fat, high carbohydrate diet on the rate
      of breast epithelial cell proliferation in women at high risk for breast cancer.
      Women were recruited from the intervention and control groups of a randomized low
      fat dietary intervention trial, breast epithelial cells were obtained by fine
      needle aspiration, and cell proliferation was assessed in these samples using
      immunofluorescent detection of Ki-67 and PCNA. The effects of needle size and
      study group on cell yield and cytologic features of the cells were also examined.
      Fifty three women (20 in the intervention group and 33 in the control group)
      underwent the biopsy procedure. Slides from 38 subjects were stained for Ki-67
      and from 14 subjects for PCNA. No cell proliferation (fluorescence) was detected
      for either Ki-67 or PCNA in any of the slides. Epithelial cell yield and number
      of stromal fragments were greater with a larger needle size. Numbers of stromal
      fragments and bipolar naked nuclei were greater in the low fat as compared to the
      control group but no differences in epithelial cell yield were observed between
      the two groups. This study confirms that fine needle aspiration biopsy is a
      feasible method of obtaining epithelial cells from women without discrete breast
      masses, but suggests that cell proliferation cannot be assessed using Ki-67 and
      PCNA in such samples.

PMID- 9150901
TI  - Prognostic significance of etiological risk factors in early breast cancer.
AB  - Several risk factors for the etiology of breast cancer have also been correlated
      with the prognosis of breast cancer. However, the published studies have yielded
      conflicting results. Women under 71 years of age with stage I, II, or III breast
      cancer were eligible for inclusion in a clinical study. 866 patients with breast
      cancer entered the study, of whom 463 had positive lymph nodes. Survival was
      analysed using Cox's proportional hazards model. Age at menarche parity, age at
      menopause and family history were not consistently related to survival. Young age
      at first full-term pregnancy was related to decreased survival (adjusted relative
      risk (RR): 1.69, 95% confidence intervals (95% CI): 1.04-2.68), but it cannot be
      excluded that this result was due to chance alone. Use of oral contraceptives was
      not correlated with survival (RR: 1.10, 95% CI: 0.80-1.51) nor was family history
      (RR: 0.93, 95% CI: 0.66-1.30). This study provided little support for the
      hypothesis that risk factors for breast cancer are related to survival.

PMID- 9150902
TI  - Hospital-related differences in breast cancer management. Analysis of an
      unselected population-based series of 1353 radically operated patients.
AB  - A retrospective review is presented of 1353 consecutive patients with
      histopathologically confirmed invasive breast carcinoma treated radically with
      curative intent during the decade 1980-89. None had received adjuvant systemic
      therapy with hormones or prolonged chemotherapy. The distribution of lymph-node
      negative (N-) and lymph-node positive (N+) patients was 75% and 25%,
      respectively. The treatment and outcome were analysed as regards conventional
      prognostic parameters, in particular considering the axillary lymph-node status
      and the responsible hospital category (General Municipal Hospitals (MH)) versus
      Comprehensive Cancer Center (CC)). The most striking difference was detected as
      regards the number of examined lymph nodes. The median number of nodes described
      at the MH was 7, as compared to 14 at the CC (p < 0.001). In patients with pT1
      tumours the highest rate of lymph-node positivity was observed when 10 or more
      axillary nodes were removed. Adjuvant radiotherapy reduced the loco-regional
      recurrence rate in the N-patients, whereas only the regional recurrences were
      reduced among the N+ patients. The five- and 10-year tumor-related survival rates
      were 86% and 76%, respectively, with no difference between the MH and the CC. As
      life-prolonging adjuvant hormone therapy and chemotherapy is now available for
      patients with axillary lymph node metastases, it is important that patients with
      breast cancer are operated adequately with the aim to remove at least 10 axillary
      lymph nodes. A thorough examination of the axillary content should be performed
      by the pathologist, and the number of resected lymph nodes and metastases should
      be reported. The establishment of nation-wide standard criteria for the
      management of breast cancer is recommended.

PMID- 9150903
TI  - Antineoplastic activity of sterically stabilized alkylphosphocholine liposomes in
      human breast carcinomas.
AB  - New sterically stabilized liposomes derived from the antitumor agent
      hexadecylphosphocholine with reduced uptake by the mononuclear phagocyte system
      and improved antitumor activities were developed and tested. The bilayer of such
      sterically stabilized liposomes consists of hexadecylphosphocholine, cholesterol
      and polyethylene glycol-linked phosphoethanolamine. The measurement of carbon
      clearance in mice shows that these stabilized liposomes, in contrast to
      conventional alkylphosphocholine liposomes, are not largely engulfed by the
      mononuclear phagocyte system. Their therapeutic activity on experimental human
      breast carcinomas MaTu. MT-1 and MT-3 was tested in nude mice. Especially in the
      MaTu models the sterically stabilized hexadecylphosphocholine liposomes resulted
      in significantly reduced tumor growth in comparison to conventional
      hexadecylphosphocholine liposomes or free hexadecylphosphocholine. The enhanced
      therapeutic efficacy of sterically stabilized hexadecylphosphocholine liposomes
      is probably related to the extended circulation time of the formulation and its
      accumulation in tumors.

PMID- 9150904
TI  - Establishment and characterisation of new cell lines from human breast tumours
      initially established as tumour xenografts in NMRI nude mice.
AB  - Human breast cancer cell lines are required as models for use in the
      understanding of breast carcinoma, and for improving the ability of cell screens
      to detect appropriate anti-cancer agents. Four human breast cancer cell lines (MT
      1, MaTu. MT-3 and MC4000) were established from human tumour xenografts grown in
      nude mice. All the lines were shown to be of human origin by karyotype analysis,
      were epithelial in morphology by both light and electron microscopy, were
      positive for cytokeratin 18, and were free from mycoplasma, bacterial, yeast and
      fungal contamination. All of the new lines were shown to be ER and PgR negative,
      while using the same procedures (i.e. radioligand binding and immunohistochemical
      staining) the positive control cell line MCF-7 was shown to be positive. MaTu had
      been previously reported as ER and PgR positive in vivo and it may be that this
      characteristic had been lost due to in vitro selection pressures. The growth
      rates of all the new breast cancer cell lines were similar and within the limits
      required for incorporation into a panel for screening anti-cancer drugs by a
      microtetrazolium based, colorimetric growth inhibition assay. Three of the lines
      (MT-1. MaTu and MC4000) were also able to grow into macroscopic colonies for use
      in a non-agar clonogenic assay. In addition, both MT-1 and MaTu formed spheroids
      and were clonogenic in soft-agar. The new lines demonstrated a wide range of
      sensitivities to anticancer agents commonly used in the treatment of breast
      cancer, and together with their corresponding xenografts are providing additional
      systems for the evaluation of new compounds.

PMID- 9150905
TI  - Guidelines for systemic therapy of early stage breast cancer.
AB  - Optimal treatment of early stage breast cancer remains an active area of study.
      An expert multidisciplinary committee reviewed clinical data on systemic therapy
      for early stage, stage I and II breast cancer. Guidelines for treatment were
      developed for Texas Oncology. P.A., the largest private practice group of
      oncologists in the United States. This group of physicians treats approximately
      5000 new breast cancer patients each year and has a major impact on oncology care
      in the state of Texas. These guidelines identify prognostic factors which help
      the practitioner in choosing treatment for patients. Subsets of patients are
      identified for whom no systemic therapy is warrented. Standard chemotherapy and
      hormonal therapy regimens are outlined for patients with early stage disease at
      increased risk for relapse. Dose intensification for high risk stage II patients
      is reviewed. Timing of therapy and the sequencing of chemotherapy and radiation
      therapy is addressed. Strategies for the follow-up of patients with a history of
      breast cancer are outlined.

PMID- 9150906
TI  - A guide for the guideline reader.

PMID- 9150908
TI  - Prefractionation of protein samples prior to two-dimensional electrophoresis.
AB  - Thousands of proteins may be visualised on a two-dimensional (2-D) gel, but only
      hundreds are present at levels sufficient for chemical analysis. Therefore,
      prefractionation of protein samples prior to 2-D polyacrylamide gel
      electrophoresis (PAGE) will be important for the investigation of proteins that
      are present at sub-picogram levels in physiological samples. We describe an
      approach to prefractionate protein samples prior to 2-D PAGE using the Gradiflow,
      which is a new (preparative) electrokinetic membrane apparatus designed to
      fractionate proteins in a number of different ways. We have fractionated human
      serum under nonreducing conditions using the 'reflux' mode, in which proteins are
      fractionated according to their relative mobility under controlled
      electrophoretic conditions, where the current is periodically reversed. We
      describe how fractionation occurs and present examples of enrichment of specific
      proteins.

PMID- 9150907
TI  - Improvement of the solubilization of proteins in two-dimensional electrophoresis
      with immobilized pH gradients.
AB  - Membrane and nuclear proteins of poor solubility have been separated by high
      resolution two-dimensional (2-D) gel electrophoresis. Isoelectric focusing with
      immobilized pH gradients leads to severe quantitative losses of proteins in the
      resulting 2-D map, although the resolution is usually high. Protein solubility
      could be improved by using denaturing solutions containing various detergents and
      chaotropes. Best results were obtained with a denaturing solution containing
      urea, thiourea, and detergents (both nonionic and zwitterionic). The usefulness
      of thiourea-containing denaturing mixtures is shown for microsomal and nuclear
      proteins as well as for tubulin, a protein highly prone to aggregation.

PMID- 9150909
TI  - Improved and simplified in-gel sample application using reswelling of dry
      immobilized pH gradients.
AB  - A simple and inexpensive methacrylate rehydration chamber was built to
      accommodate ten immobilized pH gradient (IPG) strips. In the chamber, entire IPG
      gels were used for sample application, with the protein entering the gels during
      their rehydration. For rehydration, commercially available or laboratory-made
      strips were positioned in the grooves with the gel in contact with 500 microL of
      sample for 6 h or overnight. This avoided the use of sample cups, eliminated
      precipitation at the sample application site, thus improving resolution over the
      entire pH range of the gels. It also allowed precise control of protein amounts
      and sample volumes loaded into the IPG gels, and also lowered costs of reagents
      during rehydration and equilibration owing to the reduced volumes. Up to 5 mg of
      protein can be loaded on wide IPG gels and up to 15 mg of some samples on narrow
      pH range gels.

PMID- 9150910
TI  - Very alkaline immobilized pH gradients for two-dimensional electrophoresis of
      ribosomal and nuclear proteins.
AB  - Basic proteins normally lost by the cathodic drift of carrier ampholyte focusing,
      or separated by NEPHGE with limited reproducibility, could be well separated by
      two-dimensional (2-D) electrophoresis under equilibrium conditions using
      immobilized pH gradients (IPGs) 4-10 and 6-10 using a previously published
      protocol (Gorg et al., Electrophoresis 1988, 9, 531-546). In the present study we
      have extended the pH gradient to pH 12 with IPGs 8-12, 9-12 and 10-12 for the
      analysis of very basic proteins. Different optimization steps with respect to pH
      engineering, gel composition and running conditions, such as substitution of
      acrylamide by dimethylacrylamide and addition of isopropanol with and without
      methylcellulose to the IPG rehydration solution (in order to suppress the reverse
      electroosmotic flow) were necessary to obtain highly reproducible 2-D patterns of
      ribosomal proteins from HeLa cells and mouse liver. Histones from chicken
      erythrocyte nuclei as well as total cell extracts of erythrocytes were also
      successfully separated under steady-state conditions. Due to the selectivity of
      isoelectric focusing in IPG 9-12, where the more acidic proteins abandon the gel,
      the tedious procedure of nuclei preparation prior to histone extraction can be
      omitted.

PMID- 9150911
TI  - Reproducibility of polypeptide spot positions in two-dimensional gels run using
      carrier ampholytes in the isoelectric focusing dimension.
AB  - The reproducibility of complex protein patterns in two-dimensional (2-D) gels run
      with carrier ampholytes in the first dimension has been investigated. Two
      different laboratories collaborated in the study and 18 or 19 gels were run in
      each laboratory for comparison. The electrophoresis chemicals, running devices,
      and samples were standardized in both labs. The resulting 37 gels were scanned
      with a charge-coupled device (CCD) camera and spots were located, counted,
      quantified, and matched using a commercially available image analysis system.
      Subsequently, the reproducibility of spot position was determined. To perform the
      statistical analysis, the test gels were initially each matched to a master
      reference gel. Next, three sets of 12 gels (the image analysis software database
      could analyze only 12 gels at a time) were analyzed and the isoelectric point
      (pI) and molecular weight (M(r)) positional variation of all the spots that
      matched across the gels in each set was determined. The resulting statistical
      analysis indicates very high reproducibility of the carrier ampholyte technique.

PMID- 9150912
TI  - pH changes in Immobiline gels due to low-molecular mass ion adsorption and
      conditions for salt front formation during electrophoretic desorption.
AB  - A simple theoretical model of low molecular mass ion adsorption on a weak
      exchanger is proposed. For a system containing immobilized charges in uniform
      concentration the pH change values connected with neutral salt addition and
      followed by further washing and voltage application are evaluated. The question
      of stability of the moving boundary, arising in the area near the electrodes, is
      considered for the constant current stabilization at different values of
      Immobiline concentration, pK values of Immoboline and salt concentration. The
      threshold values of ion mobility capable of providing a sharp salt front
      formation are also evaluated for conditions of strong adsorption. We found that,
      with extremely acidic Immobilines, a sharp salt front does not arise under the
      latter condition, even in the case of very high Immobiline concentrations.

PMID- 9150913
TI  - Identification of mouse liver proteins on two-dimensional electrophoresis gels by
      matrix-assisted laser desorption/ionization mass spectrometry of in situ
      enzymatic digests.
AB  - A number of proteins from a silver-stained two-dimensional (2-D) electrophoresis
      gel of mouse liver whole-cell lysate were identified by peptide mass mapping and
      sequence database searching. The excised protein spots were processed by in situ
      reduction and alkylation, followed by Lys-C digestion. The masses of the
      resulting peptide mixtures were measured with a matrix-assisted laser
      desorption/ionization (MALDI) reflection-time-of-flight mass spectrometer. These
      masses were used successfully to search a protein sequence database. Optimized
      silver staining and digestion protocols allowed proteins to be identified
      routinely at the low picomole level. The high mass accuracy and resolution
      provided by delayed extraction were important for high specificity in the
      database search. Fragment ion data obtained by MALDI post-source decay (PSD)
      measurements not only provided confirmation of peptide identification, but could
      be used to identify the protein from a single peptide without spectral
      interpretation.

PMID- 9150914
TI  - High sensitivity identification of proteins by electrospray ionization tandem
      mass spectrometry: initial comparison between an ion trap mass spectrometer and a
      triple quadrupole mass spectrometer.
AB  - Recently, we have shown that a solid-phase-microextraction/capillary
      electrophoresis device coupled to an electrospray ionization triple quadrupole
      mass spectrometer through a microelectrospray interface represents a powerful
      analytical system for the rapid, conclusive and sensitive identification of
      proteins separated by gel electrophoresis. Here we report on the successful
      coupling of the same device to an electrospray ionization ion trap mass
      spectrometer and on the comparative evaluation of the performance of the triple
      quadrupole and ion-trap-based systems. In the ion trap mass spectrometer-based
      system, using a tryptic digest of a calibrated bovine serum albumin sample, we
      achieved limits of detection in the single mass spectrometry (MS) and tandem MS
      mode, respectively, of 400 amol (if 20 microL of solution at a concentration of
      20 amol/microL was applied). The system was also successfully used to identify
      six yeast proteins isolated from a single analytical two-dimensional
      polyacrylamide gel. For the detection of unfragmented peptide ions both systems
      showed comparable sensitivity, whereas the ion-trap-based system showed superior
      performance with fragment ion spectra.

PMID- 9150915
TI  - Comparison of in-gel and on-membrane digestion methods at low to sub-pmol level
      for subsequent peptide and fragment-ion mass analysis using matrix-assisted laser
      desorption/ionization mass spectrometry.
AB  - The success of the mass spectrometric-based approaches for the identification of
      gel-separated proteins relies upon recovery of peptides, without high levels of
      ionization-suppressing contaminants, in solvents compatible with the mass
      spectrometer being employed. We sought to determine whether in-gel or on-membrane
      digestion provided a significant advantage when low to sub-pmol quantities of gel
      separated proteins were analyzed by matrix-assisted laser-desorption/ionization
      mass spectrometry (MALDI-MS) with respect to the number and size of released
      peptides. Serial dilutions of five standard proteins of M(r) 17,000 to 97,000
      (from 16 pmol to 125 fmol) were electrophoresed and subjected to in-gel digestion
      (using a microcolumn clean-up protocol, Courchesne, P.L. and Patterson, S. D.,
      BioTechniques, 1997, in press) or on-membrane digestion following blotting to the
      PVDF-based membranes, Immobilon-P and Immobilon-CD. Peptide maps were able to be
      obtained for all proteins at the detection limit of each method (Immobilon-P and
      Immobilon-CD, 0.5 pmol; and in-gel, 125 fmol), and searches of Swiss-Prot or a
      non-redundant database (> 193000 entries) successfully identified all of the
      proteins, except beta-casein. Fragment-ion spectra using a curved-field reflector
      MALDI-MS were obtained from more than one peptide per protein at loads down to
      250 fmol (except beta-casein). Using the uninterpreted data, a search of the
      nonredundant database and a six-way translation of GenBank dbEST (> 2,208,000
      entries total) was able to identify myoglobin, carbonic anhydrase II, and
      phosphorylase b.

PMID- 9150916
TI  - Sensitivity and mass accuracy for proteins analyzed directly from polyacrylamide
      gels: implications for proteome mapping.
AB  - Matrix-assisted laser desorption ionization (MALDI) mass spectra have been
      obtained directly from thin-layer isoelectric focusing (IEF) gels with as little
      as 700 femtomoles of alpha- and beta-chain bovine hemoglobin and bovine carbonic
      anhydrase, and 2 picomoles of bovine trypsinogen, soybean trypsin inhibitor, and
      bovine serum albumin all loaded onto a single lane. By soaking the gel in a
      matrix solution, matrix was deposited over the entire gel surface, allowing MALDI
      scanning down complete lanes of the one-dimensional gel. As long as matrix
      crystals were deposited finely on the surface of the gel, time-lag focusing
      techniques were capable of ameliorating some of the mass accuracy limitations
      inherent in desorbing from uneven insulator surfaces with external calibration.
      Eleven measurements on the 5 kDa alpha-subunit proteins of lentil lectin measured
      over the course of 1 h and referenced to a single calibration yielded a standard
      deviation of 0.025%. Colloidal gold staining was found to be compatible with
      desorption directly from IEF and sodium dodecyl sulfate (SDS)-polyacrylamide
      gels. This direct approach simplifies the interface between gel electrophoresis
      and mass spectrometry dramatically, making the process more amenable to
      automation.

PMID- 9150917
TI  - Rapid mass spectrometric identification of proteins from two-dimensional
      polyacrylamide gels after in gel proteolytic digestion.
AB  - We report a rapid method for identifying proteins resolved by two-dimensional
      polyacrylamide gel electrophoresis (2-D PAGE) using matrix-assisted laser
      desorption ionization-mass spectrometry (MALDI-MS). In-gel digestion was
      performed in a way such that the volume ratio of trypsin solution to gel plug was
      quantitatively controlled to promote reproducible digestion and to maximize the
      digestion yield. To make the digestion samples more compatible with MALDI-MS, the
      volatile salt ammonium bicarbonate in the digestion buffer was largely removed
      prior to peptide extraction. Samples of mixed tryptic peptides from in-gel
      digestion were used without purification to obtain molecular weights by MALDI-MS
      with alpha-cyano, 4-hydroxy-cinnamic acid as the matrix. Modifications of MALDI
      sample loading procedures improved the detection sensitivity by one half to one
      order of magnitude. The peptide mass peaks in MALDI-MS spectra were distinguished
      from those of impurities by using several types of controls, and masses were
      corrected by using trypsin autodigestion fragments as internal calibration
      standards. Two different peptide-matching computer programs were used to
      interrogate sequence databases and identify proteins. Identification was enhanced
      by generation of orthogonal data sets (by using different proteases) and by
      including experimental values of isoelectric point (pI) and molecular weight to
      exclude false entries in the candidate lists. Approximately 1% of the material
      from a spot was used in each sample loading, and nine protein spots from rat
      liver 2-D PAGE gels were identified correctly, as judged by comparison with
      identification results previously obtained from Edman sequencing. A previously
      identified low-abundance spot was not identified by MALDI-MS, presumably because
      there was insufficient material in a single gel. The sample handling procedure
      reported here should permit us to identify many 2-D PAGE protein spots of medium
      abundance.

PMID- 9150918
TI  - Detailed peptide characterization using PEPTIDEMASS--a World-Wide-Web-accessible
      tool.
AB  - In peptide mass fingerprinting, there are frequently peptides whose masses cannot
      be explained. These are usually attributed to either a missed cleavage site
      during the chemical or enzymatic cutting process, the lack of reduction and
      alkylation of a protein, protein modifications like the oxidation of methionine,
      or the presence of protein post-translational modifications. However, they could
      equally be due to database errors, unusual splicing events, variants of a protein
      in a population, or artifactual protein modifications. Unfortunately the
      verification of each of these possibilities can be tedious and time-consuming. To
      better utilize annotated protein databases for the understanding of peptide mass
      fingerprinting data, we have written the program "PEPTIDEMASS". This program
      generates the theoretical peptide masses of any protein in the SWISS-PROT
      database, or of any sequence specified by the user. If the sequence is derived
      from the SWISS-PROT database, the program takes into account any annotations for
      that protein in order to generate the peptide masses. In this manner, the user
      can obtain the predicted masses of peptides from proteins which are known to have
      signal sequences, propeptides, transit peptides, simple post-translational
      modifications, and disulfide bonds. Users are also warned if any peptide masses
      are subject to change from protein isoforms, database conflicts, or an mRNA
      splicing variation. The program is freely accessible to the scientific community
      via the ExPASy World Wide Web server, at the URL address:
      http://www.expasy.ch/www/tools.html.

PMID- 9150919
TI  - Immobilized pH gradient two-dimensional gel electrophoresis and mass
      spectrometric identification of cytokine-regulated proteins in ME-180 cervical
      carcinoma cells.
AB  - Two-dimensional (2-D) polyacrylamide gel electrophoresis combined with mass
      spectrometry is a powerful combination of technologies that allows high
      resolution separation of proteins and their rapid identification. Immobilized pH
      gradient (IPG) first-dimensional gels have several advantages over carrier
      ampholyte isoelectric focusing, including a high degree of reproducibility, good
      protein spot resolution, and a selection of pH range. Here we demonstrate the
      utility and efficacy of combining IPG 2-D gel electrophoresis with mass
      spectrometry to identify interferon-gamma- (IFN) and tumor necrosis factor (TNF)
      regulated proteins in ME-180 cervical carcinoma cells. Three cytokine-regulated
      proteins have been identified, using imidazole-zinc-stained preparative IPG 2-D
      gels and in-gel tryptic digestion followed by matrix-assisted laser desorption
      ionization time-of-flight (MALDI-TOF) mass spectrometry for determination of
      peptide masses and sequences: 1) triosephosphate isomerase, a glycolytic pathway
      enzyme, 2) proteasome subunit C3, which is important in protein degradation, and
      3) Ran, a GTP-binding protein important in cell cycle regulation, protein import
      into the nucleus, and RNA export from the nucleus.

PMID- 9150920
TI  - Identification of two-dimensional gel electrophoresis resolved yeast proteins by
      matrix-assisted laser desorption ionization mass spectrometry.
AB  - Protein extract from yeast cells growing exponentially in saline medium was
      separated by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), with
      the separation in the first dimension on a wide range immobilized pH (3-10)
      gradient. From one preparative 2-D gel a number of previously identified proteins
      were used as test material for our initial matrix-assisted laser desorption
      ionization mass spectrometry (MALDI-MS) efforts on large scale rapid protein spot
      identification. Sample preparation via in-gel trypsin digestion was slightly
      modified to be compatible to MS analysis, and via this modified procedure MS
      generated peptide mass profiles could, in most cases with good precision,
      identify the protein in question. Preferential ionization was tested on a yeast
      aldehyde dehydrogenase (ALD7), and it was shown that the ionization of some
      peptides was clearly suppressed by the presence of others. Roughly 50% of the
      observed peptide masses was found by the search routines in the database, and the
      mass measurement accuracy of the peptides was within 0.5 Da. Silver-stained gels
      could be used with good results for the generation of peptides to be analyzed by
      MALDI-MS. For one of the 2-D resolved proteins, glycerol 3-phosphatase (GPP1),
      the post-source decay (PSD) spectrum proved crucial in identification.

PMID- 9150921
TI  - The analysis of myocardial proteins by infrared and ultraviolet laser desorption
      mass spectrometry.
AB  - The use of infrared (IR) and ultraviolet (UV) matrix-assisted laser desorption
      (MALDI) mass spectrometry to analyse myocardial proteins separated by two
      dimensional (2-D) polyacrylamide gel electrophoresis (PAGE) is discussed.
      Proteins were electroblotted onto a FluoroTrans polyvinylidene difluoride (PVDF)
      membrane in order to facilitate analysis by MALDI, which represented the most
      efficient means of extracting large numbers of proteins simultaneously. Once on a
      FluoroTrans membrane, IR-MALDI was used to obtain spectra from selected protein
      spots, but no useful signals were obtained with UV MALDI. Spectra were generated
      from 46 of 50 spots analysed with protein masses from 13 to 82 kDa and
      isoelectric points (pI) 4.7-7.8. For those protein spots that had previously been
      characterised, and for which both sequence and post-translational modification
      data were known, IR-MALDI data was within plus or minus 0.5% of the expected
      mass. Some spots contained more than one protein signal, illustrating the
      increased information obtainable from MALDI, but also suggesting the limit of
      resolution of 2-D gels for separating large numbers of proteins. Attempts to
      digest proteins with specific proteases and generate peptide mass fingerprints by
      MALDI analysis on the membrane were unsuccessful with either IR or UV lasers. The
      peptides were extracted from the membrane and readily analysed by UV MALDI for
      peptide spectra. Poor data was obtained for peptide digests with IR-MALDI,
      probably because of matrix suppression by digest buffer. In order to obtain the
      maximum amount of information from blotted proteins, both IR and UV MALDI were
      required.

PMID- 9150922
TI  - Probing protein function using a combination of gene knockout and proteome
      analysis by mass spectrometry.
AB  - Recently the determination of the genome sequences of three procaryotes
      (Haemophilus influenzae, Methanococcus jannaschii and Mycoplasma genitalium) as
      well as the first eucaryotic genome (Saccharomyces cerevisiae) were completed.
      Between 40-60% of the genes were found to code for proteins to which no function
      could be assigned. We describe an approach which combines proteome analysis
      (mapping of expressed proteins isolated by two-dimensional polyacrylamide gel
      electrophoresis to the genome) with genetic manipulations to study the complex
      pattern of protein regulation occurring in Escherichia coli in response to
      sulfate starvation. We have previously described the upregulation of eight spots
      on two-dimensional (2-D) gels in response to sulfate starvation and the
      assignment of six of these to entries in the E. coli genome sequence (Quadroni et
      al., Eur. J. Biochem. 1996, 239, 773-781). Here we describe the identification of
      the remaining two proteins which are encoded in a sulfate-controlled operon in
      the 21.5' region of the E. coli genome. Upregulated protein spots were cut from
      multiple 2-D gels collected and run on a modified funnel gel to concentrate the
      proteins and remove the sodium dodecyl sulfate before digestion. The peptide
      masses obtained from the digests were used to search the SwissProt database or a
      six-frame translation of the EMBL DNA database using a peptide mass
      fingerprinting algorithm. A digest can be reanalyzed after deuterium exchange to
      obtain a second, orthogonal data set to increase the confidence level of protein
      identification. The digests of the remaining unidentified proteins were used for
      peptide fragment generation using either post-source decay in a matrix-assisted
      laser desorption ionization (MALDI) time-of-flight mass spectrometer or collision
      induced dissociation (CID) coupled mass spectrometry (MS/MS) with triple stage
      quadrupole or ion trap mass spectrometers. The spectra were used as peptide
      fragment fingerprints to search the SwissProt and EMBL databases.

PMID- 9150923
TI  - Convergence of amino acid compositions of certain groups of protein aids in their
      identification on two-dimensional electrophoresis gels.
AB  - The amino acid composition (AAC) versus the protein identity (PI) method was used
      for establishment of the identities of proteins from bovine brain and kidneys
      which were prefractionated on a CM52 cation exchanger and by preparative flat-bed
      isoelectric focusing. Established identities of proteins whose AACs converge with
      those of other members of their proper superfamily are reliable. Groups of
      convergent AACs can be extracted from protein databases using the standard root
      mean-square rule (Rmsd) with measures the difference between the AAC of chosen
      protein versus those in the database. Convergence of AACs of proteins is
      dependent on several factors such as the upper limit of Rmsd, the limits of
      variations of molecular mass (m) and isoelectric point (pI), the number of
      proteins with similar AACs present in protein databases, and the domain structure
      of proteins. AACs of many proteins remain unique if the Rmsd is maintained within
      1.5-1.0 with m +/- 3kDA and pI +/- 4. Certain groups of multidomain proteins have
      quasi-unique AACs only if the Rmsd is restrained to a value within 1.0 and 0.7.
      Convergence of AACs of certain groups of proteins may indicate that a common
      biological function exists for some members of each group. The AAC-PI method may
      become an additional search tool for protein functions.

PMID- 9150925
TI  - Comparing two-dimensional electrophoretic gel images across the Internet.
AB  - Scientists around the world often work on similar data so the need to share
      results and compare data arises periodically. We describe a method of comparing
      two two-dimensional (2-D) protein gels of similar samples created in different
      laboratories to help identify or suggest protein spot identification. Now that 2
      D gels and associated databases frequently appear on the Internet, this opens up
      the possibility of visually comparing one's own experimental 2-D gel image data
      with data from another gel in a remote Internet database. In general, there are a
      few ways to compare images: (i) slide one gel (autoradiograph or stained gel)
      over the other while back-illuminated, or (ii) build a 2-D gel computer database
      from both gels after scanning and analyzing these gels. These are impractical
      since in the first case the gel from the Internet database is not locally
      available. In the second, the costs of building a multi-gel database solely to
      answer the question of whether a spot is the same spot may be excessive if only a
      single visual comparison is needed. We describe a distributed gel comparison
      program (URL: http://www-lmmb.ncifcrf.gov/flicker) which runs on any World Wide
      Web (WWW) connected computer and is invoked from a Java-capable web browser. One
      gel image is read from any Internet 2-D gel database (e.g. SWISS-2DPAGE) and the
      other may reside on the investigator's computer. Images may be more easily
      compared by first applying spatial warping or other transforms interactively on
      the user's computer. First, regions of interest are "landmarked" with several
      corresponding points in each gel image, then one gel image is warped to the
      geometry of the other. As the two gels are rapidly alternated, or flickered, in
      the same window, the user can slide one gel past the other to visually align
      corresponding spots by matching local morphology. This flicker-comparison
      technique may be applied to analyzing other types of one-dimensional and 2-D
      biomedical images.

PMID- 9150924
TI  - Proteome analysis of glycoforms: a review of strategies for the
      microcharacterisation of glycoproteins separated by two-dimensional
      polyacrylamide gel electrophoresis.
AB  - Preparative two-dimensional polyacrylamide electrophoresis (2-D PAGE) is a method
      of separation which for the first time allows protein isoforms to be readily
      purified for subsequent analysis. The profile of the 2-D separation of the
      protein complement (proteome) of eukaryotic cells and tissues typically contains
      obvious 'trains' of spots which differ in pI and/or apparent molecular mass.
      These are usually isoforms of the same protein and result from post-translational
      modifications. There is growing evidence that alterations to the glycosylation
      and/or phosphorylation of a protein can be correlated with developmental and
      pathological changes; these changes can be visualised on the 2-D separation. It
      is not clear, however, how these modifications alter the structural properties of
      the protein and affect their migration in this mode of separation. Strategies
      need to be developed to obtain a more detailed understanding of the reason for
      the appearance of isoforms as discrete spots on 2-D PAGE. Standard proteins,
      fetuin and ovalbumin, were used to monitor the effect of the removal of glycans
      and phosphates on the migration of the glycoproteins in the 2-D system. The
      isoforms were not simply explained by the presence or absence of a single
      modification. To further investigate the reasons for the different migration of
      the isoforms it is necessary to characterise the modifications in more detail.
      Unlike protein analysis, until recently the available methodology for the
      analysis of the glycans attached to proteins has not been sensitive enough to
      allow analysis of single spots in gels or blots resulting from 2-D
      electrophoresis. In this paper we review current and future strategies for
      characterisation of protein modifications using single spots from 2-D gels.

PMID- 9150926
TI  - Construction of HSC-2DPAGE: a two-dimensional gel electrophoresis database of
      heart proteins.
AB  - The dissemination of information relating to the characterisation of proteins
      from two-dimensional electrophoresis (2-DE) gel databases is essential for their
      effective utilisation in the study of protein expression in cell biology. Since
      the inception of the World Wide Web and the pioneering development of SWISS
      2DPAGE as a tool for retrieving information on proteins separated by 2-DE, the
      Internet has become the method of choice for disseminating and accessing
      information on 2-DE protein databases. At Harefield we have established HSC
      2DPAGE which is an advanced interface for accessing protein database relating to
      heart disease. The Web site currently includes databases of proteins from human,
      dog and rat ventricular tissue and a human endothelial cell line. The databases
      are searchable individually or as a whole by remote keyword searches. Each
      database is represented by both synthetic (computer generated) and real (scanned
      gel) clickable images upon which characterised protein spots are highlighted by
      hyperlinked symbols. The database conforms to all the rules proposed for
      federated 2-DE protein databases and individual protein entries are linked to
      other protein databases such as SWISS-PROT by active cross-references. This paper
      describes the construction of HSC-2DPAGE, its maintenance, and access via the
      Internet.

PMID- 9150927
TI  - Towards design and comparison of World Wide Web-accessible myocardial two
      dimensional gel electrophoresis protein databases.
AB  - In addition to the recently published HEART-2DPAGE--a myocardial World Wide Web
      accessible 2-DE gel protein database--the usage and installation of software
      tools are described with regard to the hard- and software environments. Further,
      access to the HEART-2DPAGE from other two-dimensional electrophoresis (2-DE)
      databases using name or accession code of a protein is now available. Moreover,
      database images, published in the myocardial HSC-2DPAGE and HEART-2DPAGE
      databases are compared. Using the warping tool of the common image processing
      system Khoros the database images are matched and added in order to visualize the
      effects of warping. The application of such image processing tools is aimed at
      improving the comparability of protein spot patterns of different gel images
      available through the net.

PMID- 9150928
TI  - An on-line two-dimensional polyacrylamide gel electrophoresis protein database of
      adult Drosophila melanogaster.
AB  - An annotated two-dimensional polyacrylamide gel electrophoresis (2-D PAGE)
      protein database of adult Drosophila melanogaster has been constructed, based on
      the protein patterns of heads, thoraces and abdomens of adult male and female
      Drosophila melanogaster. About 1200 major protein spots are catalogued. Common
      proteins, found in all body parts, as well as bodypart- and sex-specifically
      expressed proteins are reported. Of the major proteins, 91, or 7.5%, are
      differentially expressed in the two sexes or in different body parts, at least in
      part reflecting specific functional requirements. At the present time 43
      proteins, or about 3.5% of the detected proteins, have been identified. These
      data can be accessed interactively from our World Wide Web (WWW) server through
      clickable inline gel images and hypertext links. Identified protein spots are
      cross-referenced, through hypertext links, to the SWISS-PROT annotated database
      of protein primary sequences and the Fly-Base database of Drosophila genomic
      data. Our reference gels can be used to gain immediate access to protein spot
      identify and to the pattern of differentially expressed proteins in Drosophila
      melanogaster. The work presented in this article ties together information from
      protein 2-D PAGE, molecular biology and genetics and offers a uniform way to
      access this large volume of data.

PMID- 9150929
TI  - The Dictyostelium discoideum proteome--the SWISS-2DPAGE database of the
      multicellular aggregate (slug).
AB  - The cellular slime mold Dictyostelium discoideum is a eukaryotic microorganism
      which has developmental life stages attractive to the cell and molecular
      biologist. By displaying the two-dimensional polyacrylamide gel electrophoresis
      (2-D PAGE) protein map of different developmental stages, the key molecules can
      be identified and characterised, allowing a detailed understanding of the D.
      discoideum proteome. Here we describe the preparation of reference gel of the D.
      discoideum multicellular aggregate, the slug. Proteins were separated by 2-D PAGE
      with immobilised pH gradients (pH 3.5-10) in the first dimension and sodium
      dodecyl sulfate (SDS)-PAGE in the second dimension. Micropreparative gels were
      electroblotted onto polyvinylidene difluoride (PVDF) membranes and 150 spots were
      visualised by amido black staining. Protein spots were excised and 31 were
      putatively identified by matching their amino acid composition, estimated
      isoelectric point (pI) and molecular weight (M(r)) against the SWISS-PROT
      database with the ExPASy AAcompID tool (http://
      expasy.hcuge.ch/ch2d/aacompi.html). A total of 25 proteins were identified by
      matching against database entries for D. discoideum, and another six by cross
      species matching against database entries for Saccharomyces cerevisiae proteins.
      This map will be available in the SWISS-2DPAGE database.

PMID- 9150930
TI  - Large-scale protein modelling and integration with the SWISS-PROT and SWISS
      2DPAGE databases: the example of Escherichia coli.
AB  - Knowledge-based molecular modelling of proteins has proven useful in many
      instances, including the rational design of mutagenesis experiments, but it has
      generally been limited by the availability of expensive computer hardware and
      software. To overcome these limitations, we developed the SWISS-MODEL server for
      automated knowledge-based protein modelling. The SWISS-MODEL server uses the
      Brookhaven Protein Data Bank as a source of structural information and
      automatically generates protein models for sequences which share significant
      similarities with at least one protein of known three-dimensional structure. We
      have now used the software framework of the server to generate large collections
      of protein models, and established the SWISS-MODEL Repository, a new database for
      automatically generated and theoretical protein models. This repository is
      directly integrated with the SWISS-PROT and SWISS-2DPAGE databases through the
      ExPASy World Wide Web server (URL is http://expasy.hcuge.ch). Here we present an
      illustration of this process by an application to the Escherichia coli sequences.

PMID- 9150931
TI  - The assay development of a molecular marker for transmissible spongiform
      encephalopathies.
AB  - The transmissible spongiform encephalopathies are a group of neurodegenerative
      diseases which include Creutzfeldt-Jakob disease (CJD) in humans, scrapie in
      sheep, and bovine spongiform encephalopathy (BSE) in cattle. Two-dimensional
      electrophoresis of proteins was previously used to identify two marker proteins,
      130/131, which are selectively present in the cerebrospinal fluid (CSF) of
      patients with CJD and not in patients with other dementias. The recent
      characterization of these proteins by amino acid sequencing has identified them
      as members of the 14-3-3 family of proteins. Polyclonal antibodies against 14-3-3
      (all isoforms), 14-3-3 gamma, 14-3-3 beta, and 14-3-3 theta are immunoreactive
      with a 30 kDa marker band from CJD CSF. Silver staining of two-dimensional
      electrophoresis separated BSE CSF proteins does not identify a similar marker.
      However, 14-3-3 immunoreactivity is found in cattle CSF when these proteins are
      blotted to polyvinylidene difluoride but not when blotted to nitrocellulose.

PMID- 9150932
TI  - Characterization of target antigens from anti-neutrophil cytoplasmic antibodies
      in autoimmune hepatitis type-I.
AB  - The occurrence of anti-neutrophil cytoplasmic antibodies (ANCA) has been
      described in sera of patients with autoimmune hepatitis (AIH). The significance
      of this finding remains uncertain and the nature of the target antigen(s) has not
      yet been defined. We studied 32 sera from patients with AIH type-I and prepared
      extracts of human neutrophils to identify the target antigen(s). A 43 kDa
      dominant immunoreactive protein was found and identified as the cytoskeletal
      component actin. Initial studies to define the antigenic determinants identified
      three different actin domains.

PMID- 9150933
TI  - Two-dimensional electrophoretic analysis of human milk-fat-globule membrane
      proteins with attention to apolipoprotein E patterns.
AB  - Two-dimensional (2-D; Iso Dalt method) electrophoresis was done on lipid membrane
      fractions from human milk samples collected in polypropylene tubes at home by the
      mother. The samples represent milk from two weeks to ten months post partum.
      Identification was made by immunoassay of Western blots. Apolipoprotein E was not
      easily seen on silver-stained gels because concentration is small and spots
      overlap another protein. Blot assays show a more complex pattern than 34 kDa
      plasma apo E with molecular size isoforms at 36 kDa, 34 kDa, 20 kDa and 15 kDa.
      One sample was negative for apo E. Apo E plays an important role in lipid
      transport in tissue and in the brain. It is synthesized in a variety of tissues
      by specific cells. Milk may reflect several sources.

PMID- 9150934
TI  - Computer-supported analysis (MegaBlot) of allopurinol-induced changes in the
      autoantibody repertoires of rats suffering from experimental lens-induced
      uveitis.
AB  - Using a new quantitative immunoblot technique (MegaBlot and artificial neural
      network) sera of rats with lens-induced uveitis (LIU) were tested against Western
      blots (WB) of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE) separations of protein fractions from rat lenses. The blots were scanned
      using digital image analysis and evaluated by multivariate analysis of
      discriminance and an artificial neural network. Five groups of LIU rats (male
      Wistar rats, n = 28) were investigated: no treatment, single doses of
      methylprednisolone (MPR; 7.5 mg/kg body weight, intravenous), allopurinol (AL; 50
      mg/kg body weight, intravenous), a combination of both drugs (AL and MPR), and
      repeated application of AL (ALFR; 50 mg/kg body weight intravenous every 2 weeks
      during the immunization period and a daily dose of approximately 25 mg/kg body
      weight, orally). ALFR, MPR, and MPRAL show statistically significant
      immunological effects in LIU treatment. Classification of WBs using both
      discriminance analysis or neural network resulted in 100% correct assignment; and
      82% (discriminance analysis) and 86% (neural network) of WBs were correctly
      assigned using only unknown blots for classification (not studied before). The
      MegaBlot technique is able to detect therapeutically induced changes in
      autoantibody repertoires allowing therapeutic control and a prognostic view of
      treatment.

PMID- 9150935
TI  - Acute-phase proteins in perinatal human plasma.
AB  - Plasma from eight newborns (4 pre-term and 4 full-term) with early-onset (< 72 h)
      sepsis and six apparently healthy controls was analyzed. The presence of spots
      identified as haptoglobin and serum amyloid A protein was the electrophoretic
      result most consistently associated with disease. Time course monitoring showed
      rises, peaks and declines of spot intensity as expected for acute-phase proteins
      induced by transient stimuli. Haptoglobin beta chains appear to be undersialated
      in pre-term newborns, whereas post-translational modifications of alpha chains
      and serum amyloid A protein are similar to those observed in adults. The
      undersialation of beta chain and occurrence of alpha chain phenotypes different
      from those found in maternal serum indicate that perinatal haptoglobin originates
      from neonatal synthesis.

PMID- 9150936
TI  - Improved electrophoretic separation and immunoblotting of beta-amyloid (A beta)
      peptides 1-40, 1-42, and 1-43.
AB  - Beta-amyloid peptides (A beta peptides) form the main protein component of the
      amyloid deposits found in the brains of Alzheimer's disease (AD) patients.
      Soluble A beta peptides, which are proteolytic fragments of the amyloid-precursor
      protein (APP) are constitutively secreted by cells expressing APP during normal
      metabolism [1] and are also present in human plasma and cerebrospinal fluid [2].
      Missense mutations in Codon 717 of the APP gene are responsible for a small
      percentage of inherited AD cases (FAD) and increase the amount of A beta peptides
      containing additional carboxy terminal amino acids (A beta 1-42, A beta 1-43) [3,
      4]. Recent findings indicate that FAD mutations in the presenilin 1 and 2 genes
      also increase the amount of these longer A beta peptides [5]. A beta 1-42
      polymerizes more rapidly in vitro [6] than A beta 1-40 and has been identified as
      the major component of the brain amyloid deposits [7-9]. We recently developed a
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) system [10]
      for the separation of these two peptides. Here we describe a modified version of
      the original SDS-PAGE procedure, which allows the separation of A beta 1-40, A
      beta 1-42, and A beta 1-43 for the first time. Detection of the three A beta
      peptides in the lower ng and pg range is realized by optimized silver staining or
      immunoblot procedures. These nonradioactive methods may validate results obtained
      by ELISA procedures used to study the metabolic fate of APP. They may help to
      define the neurotoxic potential of the longer A beta peptides in relation to
      their aggregation state.

PMID- 9150937
TI  - A comparison of selected mRNA and protein abundances in human liver.
AB  - In order to obtain an estimate of the overall level of correlation between mRNA
      and protein abundances for a well-characterized pharmaceutically relevant
      biological system, we have analyzed human liver by quantitative two-dimensional
      electrophoresis (for protein abundances) and by Transcript Image methodology (for
      mRNA abundances). Incyte's LifeSeq database was searched for expressed sequence
      tag (EST) sequences corresponding to a series of 23 proteins identified on 2-D
      maps in the Large Scale Biology (LSB) Molecular Anatomy database, resulting in
      estimated abundances for 19 messages (4 were undetected) among 7926 liver clones
      sequenced. A correlation coefficient of 0.48 was obtained between the mRNA and
      protein abundances determined by the two approaches, suggesting that post
      transcriptional regulation of gene expression is a frequent phenomenon in higher
      organisms. A comparison with published data (Kawamoto, S., et al., Gene 1996,
      174, 151-158) on the abundances of liver mRNAs for plasma proteins (secreted by
      the liver) suggests that higher abundance messages are strongly enriched in
      secreted sequences. Our data confirms this: of the 50 most abundant liver mRNAs,
      29 coded for secreted proteins, while none of the 50 most abundant proteins
      appeared to be secreted products (although four plasma and red blood cell
      proteins were present in this group as contaminants from tissue blood).

PMID- 9150938
TI  - Identification of ADP-ribosylation factor-6 in brush-border membrane and early
      endosomes of human kidney proximal tubules.
AB  - The expression and distribution of ADP-ribosylation factor (ARF) small GTP
      binding proteins in kidney tissue was examined. Various anti-ARF antibodies were
      raised against purified rec-ARF 1 and rec-ARF 6 and their specificity was
      determined. Using indirect immunofluorescence analysis of intact kidney, ARF
      proteins were found to be predominantly expressed in kidney tubules as compared
      to glomeruli. This result was further supported by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis of
      purified human kidney glomeruli and proximal tubules. Both ARF 1 and ARF 6 were
      detected in purified human glomeruli and proximal tubules; however, ARF 1 was
      more abundant than ARF 6 in these kidney structures. Brush-border membrane
      vesicles (BBMV) and early endosomes (EE) derived from the receptor-mediated
      endocytosis pathway were isolated from purified proximal tubules of rat, dog and
      human kidney using a combination of magnesium precipitation and wheat-germ
      agglutinin negative selection techniques. We demonstrated that ARF 6 is
      associated with BBMV and with EE derived from receptor-mediated endocytosis
      pathway of human kidney proximal tubules. Using a combination of SDS-PAGE and
      quantitative enhanced chemiluminescence Western blot analysis, the quantification
      of the ARF 6 distribution in membrane and cytoplasmic fractions of proximal
      tubules was made and its predominance in membrane fractions was demonstrated. By
      analogy with the functional role of ARF 1 in Golgi protein transport, we suggest
      that ARF 6 may play an important role in the regulation of receptor-mediated
      endocytosis and protein reabsorption by kidney proximal tubules.

PMID- 9150939
TI  - Spermatocytes and round spermatids of rat testis: the difference between in vivo
      and in vitro protein patterns.
AB  - During mammalian spermatogenesis meiotic cell division and spermiogenesis occurs.
      Gene expression during this process is temporally regulated at the
      transcriptional and translational levels but the mechanisms are not well
      understood. In this publication we have investigated the synthesis of proteins in
      vitro to detect the proteins with a high metabolic turnover and to compare them
      with the in vivo protein map. RNA of spermatocytes and round spermatid cell
      populations, purified by centrifugal elutriation, and total testis was isolated.
      The poly A+ mRNA fraction was translated using a rabbit reticulocyte lysate. The
      translation products were separated by two-dimensional (2-D) gel electrophoresis
      using nonlinear 3.5-10 immobilized pH gradients for the first-dimensional
      separation. The gels with 35S-translated proteins were transferred onto
      polyvinylidene difluoride (PVDF) membranes and scanned using a phosphorimager. A
      highly reproducible and complex protein pattern was obtained using this
      methodology. Only rat testis messages were translated. Using Melanie 2 software
      we could compare and detect more than 1000 proteins on 2-D radioactive images.
      Some changes could be observed in protein expression between the different cell
      types but they were not statistically significant. The comparison between the 2-D
      rat testis map and the in vitro translated patterns show no matching between any
      spots. This result suggests that the post-transcriptional modifications occurring
      in the reticulocyte system are not the same as those that occur in vivo in the
      testis. Rabbit reticulocyte proteins were detected by staining PVDF membranes
      with colloidal gold. Rat testis and reticulocyte patterns were completely
      different.

PMID- 9150940
TI  - "Active" two-dimensional electrophoresis of rat liver DNA-polymerase alpha.
AB  - The approach of so-called active gel analysis was used to determine the position
      and appearance of the catalytic subunit of rat liver DNA polymerase alpha on a
      two-dimensional (2-D) electrophoretic map. In this case a polyacrylamide gel
      containing DNA was used for the second dimension. DNA presence does not change
      the 2-D protein pattern but makes it possible to conduct a polymerase reaction
      directly in the gel after separation. A crude extract of rat liver nuclei was
      used for analysis. The extract is quickly isolated and contains mainly DNA
      polymerase alpha activity. It was shown that this enzyme restores its activity
      after 2-D electrophoresis and sodium dodecyl sulfate (SDS) elution. After
      polymerase reaction with labeled dNTPs and autoradiography, the catalytic
      polypeptide or, rather, polypeptide cluster is revealed as chains of spots
      (possibly because of the presence of different hydrolyzed and phosphorylated
      forms). These spots are located on the 2-D electrophoretic map in the region
      corresponding to molecular masses of 160, 140, and 130 kDa and pI 5.5-6.2.

PMID- 9150941
TI  - Two-dimensional gel electrophoresis of Caenorhabditis elegans homogenates and
      identification of protein spots by microsequencing.
AB  - Employing isoelectric focusing on immobilized pH gradients followed by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) we have obtained a
      map of C. elegans proteins, from a mixed culture containing all developmental
      stages, presenting over 2000 spots within the window of isoelectric points (pI)
      3.5-9 and a molecular mass of 10-200 kDa. Edman microsequencing yielded
      successful results in 12 out of 24 analyzed spots. All but one of the N-terminal
      sequences retrieved C. elegans sequences in cosmid and/or expressed sequence tag
      clones. Structurally related protein sequences found in data banks included
      enzymes in energy metabolism (cytochrome oxydase, ATP synthase, enolase), a fatty
      acid-binding protein, a translationally controlled tumor protein, an unknown C.
      elegans protein, an acidic ribosomal protein, a titin-like protein, a G-protein
      beta chain, cyclophilin, and cathepsin D. Experimental determination of N-termini
      allowed us to define sites of signal cleavage providing further information on
      the physiological role of the newly found C. elegans proteins. This report
      demonstrates the possibility of two-dimensional gel electrophoresis and Edman
      microsequencing in the elucidation of C. elegans proteome.

PMID- 9150942
TI  - Characterization of Chlamydia trachomatis l2-induced tyrosine-phosphorylated HeLa
      cell proteins by two-dimensional gel electrophoresis.
AB  - Chlamydia trachomatis is an obligate intracellular bacteria, inducing its own
      uptake in nonprofessional phagocytes either by phagocytosis or pinocytosis. We
      have previously shown that C. trachomatis L2 induces tyrosine phosphorylation of
      eukaryotic proteins upon their entry by phagocytosis. In this paper we
      characterize the tyrosine-phosphorylated proteins by two-dimensional gel
      electrophoresis. In immunoblotting with anti-phosphotyrosine antibodies of C.
      trachomatis L2-infected HeLa cells, but not with uninfected cells, two rows of
      spots were observed with a molecular mass of 69 and 71 kDa and pI from 5.0 to
      5.2. In addition, a single spot of 100 kDa and pI 6.2 was observed.

PMID- 9150943
TI  - Characterisation of wool intermediate filament proteins separated by
      micropreparative two-dimensional electrophoresis.
AB  - Wool intermediate filament proteins (IFP) are a subclass of the cytokeratins, a
      group of structural proteins which form intermediate filaments in many cell
      types. Post-translational modifications, such as phosphorylation, play an
      important role in the control of intermediate filament assembly. Two-dimensional
      electrophoresis has previously been used to study the IFP distribution in wools
      with different physical characteristics. Charge heterogeneity has been observed
      in Type I and Type II IFP. In a previous study, two-dimensional electrophoresis
      of alkaline phosphatase-treated wool protein extracts was used to show that Type
      II IFP are phosphorylated. To facilitate post-separation analysis,
      micropreparative two-dimensional electrophoresis was used to separate milligram
      quantities of wool protein. Direct phosphoamino acid analysis has confirmed the
      presence of phosphorylation on serine residues on Type II IFP, whose identity was
      confirmed by amino acid compositional analysis. The isoelectric points of Type I
      IFP are very similar and they do not separate completely on the commercially
      available pH 4-7 immobilized pH gradients (IPG) used in this study. In situ
      tryptic digestion followed by automated Edman sequencing of the high performance
      liquid chromatography (HPLC)-separated peptides was used to confirm the identity
      of this group as Type I IFP. To improve the separation of the Type I IFP it will
      be necessary to use narrow range IPGs such as Immobiline DryPlates which are
      available from Pharmacia Biotech, in the pH ranges 4.2-4.9, 4.5-5.4, 5.0-6.0 and
      5.6-6.6.

PMID- 9150944
TI  - A two-dimensional electrophoresis database of human breast epithelial cell
      proteins.
AB  - As sequencing of the human genome progresses, attention is turning to when and
      where specific genes are being expressed and how that expression is regulated.
      The human breast, with the highly specific, but transient, function of milk
      production (lactation), exemplifies human gene regulation. The molecular
      mechanisms for the dramatic structural and functional changes involved in
      shifting from lactation-capable to lactation-incapable tissue are poorly
      understood, as are the mechanisms that result in deviation from normal breast
      cell growth into different types of breast neoplasms. We are using quantitative
      two-dimensional electrophoresis (2-DE) to determine which proteins are present in
      different types of human breast cells (milk-producing and -nonproducing, estrogen
      receptor-positive and -negative, normal and malignant) and which proteins change
      in abundance in response to stimuli that trigger cell differentiation, growth, or
      death. A composite map of proteins found in human breast cells is being generated
      and used as an index of human genes that are differentially expressed, both
      qualitatively and quantitatively. Proteins found in 15 different types of human
      breast cells, two from healthy tissue (from milk and reduction mammoplasty
      tissue) and 13 from tumor tissue, are now included in the composite map. Copies
      of the human breast epithelial cell protein map are available on the World Wide
      Web (URL: http:(/)/www.anl.gov/CMB/PMG/ projects/index_hbreast.html) with links
      to quantitative data and identifications for proteins found to be differentially
      expressed in these epithelial cells. Links to the Swiss-Prot and enzyme metabolic
      pathway databases are also provided. The World Wide Web presentation is designed
      to allow public access to the available 2-DE data together with logical
      connections to databases providing genome-related information.

PMID- 9150946
TI  - Two-dimensional electrophoretic analysis of human breast carcinoma proteins:
      mapping of proteins that bind to the SH3 domain of mixed lineage kinase MLK2.
AB  - MLK2, a member of the mixed lineage kinase (MLK) family of protein kinases, first
      reported by Dorow et al. (Eur. J. Biochem. 1993, 213, 701-710), comprises several
      distinct structural domains including an src homology-3 (SH3) domain, a kinase
      catalytic domain, a unique domain containing two leucine zipper motifs, a
      polybasic sequence, and a cdc42/rac interactive binding motif. Each of these
      domains has been shown in other systems to be associated with a specific type of
      protein interaction in the regulation of cellular signal transduction. To study
      the role of MLK2 in recruiting specific substrates, we constructed a recombinant
      cDNA encoding the N-terminal 100 amino acids of MLK2 (MLK2N), including the SH3
      domain (residues 23-77), fused to glutathione S-transferase. This fusion protein
      was expressed in Escherichia coli, purified using gluthathione-Sepharose affinity
      chromatography and employed in an affinity approach to isolate MLK2-SH3 domain
      binding proteins from lysates of 35S-labelled MDA-MB231 human breast tumour
      cells. Electrophoretic analysis of bound proteins revealed that two low-abundance
      proteins with a molecular weights (Mr) of approximately 31,500 and approximately
      34,000, bound consistently to the MLK2N protein. To establish accurately the Mt /
      isoelectric point (pI) loci of these MLK2-SH3 domain binding proteins, a number
      of abundant proteins in a two-dimensional electrophoresis (2-DE) master gel were
      identified to serve as triangulation marker points. Proteins were identified by
      (i) direct Edman degradation following electroblotting onto polyvinylidene
      difluoride (PVDF) membranes, (ii) Edman degradation of peptides generated by in
      gel proteolysis and fractionation by rapid (approximately 12 min) microbore
      column (2.1 mm ID) reversed-phase high performance liquid chromatography (HPLC),
      (iii) mass spectrometric methods including peptide-mass fingerprinting and
      electrospray (ESI)-mass spectrometry (MS)-MS utilizing capillary (0.2-0.3 mm ID)
      column chromatography, or (iv) immunoblot analysis. Using this information, a
      preliminary 2-DE protein database for the human breast carcinoma cell line MDA
      MB231, comprising 21 identified proteins, has been constructed and can be
      accessed via the World Wide Web (URL address: http:(/)/
      www.ludwig.edu.au/www/jpsl/jpslhome.htm l).

PMID- 9150945
TI  - Analysis of polypeptide expression in benign and malignant human breast lesions.
AB  - Results of two-dimensional electrophoresis (2-DE) analyses of human breast
      carcinoma are described. Tumor cells were extracted and purified from breast
      carcinomas with different proliferative indeces and degrees of genomic stability.
      Cells purified from fibroadenoma tissue served as controls for benign cells. The
      following results were observed: (i) Analysis of samples from different areas of
      the same tumor showed a high degree of similarity in the pattern of polypeptide
      expression. Similarly, analysis of two tumors and their metastases revealed
      similar 2-DE profiles. (ii) In contrast, large variations were observed between
      different lesions with comparable histological characteristics. Larger
      differences in polypeptide expression were observed between potentially highly
      malignant carcinomas compared to comparisons of less malignant lesions. These
      differences were in the same order of magnitude as those observed comparing a
      breast carcinoma to a lung carcinoma. (iii) The levels of all cytokeratin forms
      resolved (CK7, CK8, CK15, and CK18) were significantly lower in carcinomas
      compared to fibroadenomas. (iv) The levels of high molecular weight tropomyosins
      (1-3) were lower in carcinomas compared to fibroadenomas. The expression of
      tropomyosin-1 was found to be 1.7-fold higher in primary tumors with metastatic
      spread to axillar lymph nodes compared to primary tumors with no evidence of
      metastasis (p < 0.05). (v) The expression of proliferating cell nuclear antigen
      (PCNA) and some members of the stress protein family (pHSP60, HSP90, and
      calreticulin) were higher in carcinomas. We conclude that malignant progression
      of breast carcinomas results in large heterogeneity in polypeptide expression
      between different tumors, but that some common themes such as decreased
      expression of cytokeratin and tropomyosin polypeptides can be discerned.

PMID- 9150948
TI  - A two-dimensional gel database of human colon carcinoma proteins.
AB  - The master two-dimensional gel database of human colon carcinoma cells currently
      lists cellular proteins from normal crypts and the colorectal cancer cell lines
      LIM 1863, LIM 1215 and LIM 1899 (Ward et al., Electrophoresis 1990, 11, 883-891;
      Ji et al., Electrophoresis 1994, 15, 391-405). Updated two-dimensional
      electrophoretic (2-DE) maps of cellular proteins from LIM 1215 cells, acquired
      under both nonreducing and reducing conditions, are presented. Fifteen cellular
      proteins are identified in the reducing 2-DE gel map, and seven in the
      nonreducing gel map, along with a tabular listing of their M(r)/pI loci and mode
      of identification. We also include our mass spectrometric based procedures for
      identifying 2-DE resolved proteins. This procedure relies on a combination of
      capillary column (0.10-0.32 mm internal diameter) reversed-phase HPLC peptide
      mapping of in-gel digested proteins, peptide mass fingerprinting, sequence
      analysis by either collision-induced dissociation or post-source-decay
      fragmentation, and protein identification using available database search
      algorithms. These data, and descriptions of the micro-techniques employed in this
      laboratory for identifying 2-DE resolved proteins can be accessed via the
      internet URL: http:(/)/www.ludwig.edu.au.

PMID- 9150947
TI  - Renal cell carcinoma and normal kidney protein expression.
AB  - Renal cell carcinoma (RCC), a human kidney cancer from the proximal tubular
      epithelium, accounts for about 3% of adult malignancies. Molecular and
      cytogenetic analysis have highlighted deletions, translocations, or loss of
      heterozygosity in the 3p21-p26, a putative RCC locus, as well as in 6q, 8p, 9pq,
      and 14pq. Studies on phenotypic expression of human kidney tissue and on post
      translational modifications in RCC have not yet provided a marker for early renal
      cell carcinoma diagnosis. Current diagnostic methods do not help to detect the
      tumor before advanced stages. We therefore used two-dimensional polyacrylamide
      gel electrophoresis (2-D PAGE) to study normal and tumor kidney tissues in ten
      patients suffering from RCC. A human kidney protein map in the SWISS-2DPAGE
      database accessible through the ExPASy WWW Molecular Biology Server was
      established. Of 2789 separated polypeptides, 43 were identified by gel
      comparison, amino acid analysis, N-terminal sequencing, and/or immunodetection.
      The comparison between normal and tumor kidney tissues showed four polypeptides
      to be absent in RCC. One of them was identified as ubiquinol cytochrome c
      reductase (UQCR), whose locus has elsewhere been tentatively assigned to
      chromosome 19p12 or chromosome 22. A second polypeptide was identified as
      mitochondrial NADH-ubiquinone oxido-reductase complex I whose locus is located on
      chromosome 18p11.2 and chromosome 19q13.3. These result suggest that the lack of
      UQCR and of mitochondrial NADH-ubiquinone oxidoreductase complex I expression in
      RCC may be caused by unknown deletions, or by changes in gene transcription or
      translation. It might indicate that mitochondrial disfunction plays a major role
      in RCC genesis or evolution.

PMID- 9150950
TI  - Specific sample preparation in colorectal cancer.
AB  - Large tissue samples from ten patients operated for colorectal cancer were
      prepared in the operating room in iced phosphate buffered saline, containing
      ethylene diaminetetraacetic acid and protease inhibitors. After cutting the
      specimens into small fragments, the tissues were gently pressed through a steel
      mesh. Membranes were permeabilized in chilled ethanol 70% to allow cytosolic
      fluoresceine isothiocyanate labeling, performed with anti-cytokeratin (CAM 5.2)
      antibodies. Samples were quantitatively sorted with a fluorescence activated cell
      sorter (FACS) and denatured before processing separation by two-dimensional
      electrophoresis on polyacrylamide gels. This procedure made it possible to sample
      about 4 x 10(7) viable normal and tumoral cells before fixation, and up to 4 x
      10(6) cells after FACS. The gels run before and after fixation showed no major
      differences. The rate of cytokeratin-positive cells in the samples was the
      following (mean, CI 5-95%): mucosa 29.5% (8.9-66.7%), tumor 44.3% (6.6-94.8%).
      The epithelial cell content in colorectal cancer and normal mucosa shows
      important intersample variations. This is important for any comparison of fresh
      samples, whether at DNA, RNA, or at the protein level. We propose a method
      allowing the preparation of pure epithelial cell samples from normal and tumoral
      colonic fresh mucosa.

PMID- 9150949
TI  - Electrophoretic analysis of the novel antigen for the gastrointestinal-specific
      monoclonal antibody, A33.
AB  - The murine monoclonal antibody A33 (mAbA33) recognises a human cell membrane
      associated antigen selectively expressed in epithelial cells of the lower
      gastrointestinal tract and > 90% of colonic cancers, but is not detected in a
      wide range of other normal tissues by immunohistochemical analysis. In phase I/II
      clinical triasl, mAbA33 has been shown to target advanced colon cancers and the
      humanized version is currently being evaluated in therapy studies. Although the
      mAbA33 has been well characterised by immunohistochemical and clinical studies,
      until recently, the target antigen has remained poorly defined. This was largely
      attributable to the antigenic determinant recognised by mAbA33 being dependent on
      the native spatial conformation of the A33 antigen which impeded its
      identification by conventional two-dimensional electrophoresis (2-DE) and
      immunoblot analysis. We have developed an immunoblot method, based on
      nonreducing/non-urea precast 2-DE gels, that has facilitated the purification of
      the detergent (0.3% Triton X-100) solubilised A33 antigen from the human colon
      cancer cell lines LIM1215 and SW1222. Under these 2-DE conditions, the A33
      antigen electrophoreses with an apparent M(r) approximately 41000 and pI 5.0-6.0.
      Attempts to isolate the A33 antigen from 2-DE gels for direct structural analysis
      were unsuccessful, due to its co-electrophoresis with actin and cytokeratin
      proteins. However, using Western blot and biosensor detection the A33 antigen has
      been purified chromatographically and N-terminal sequence analysis was possible.
      Using polyclonal antibodies raised against a synthetic peptide corresponding to
      the N-terminal region of the A33 antigen we have used Western blot analysis to
      localise the molecule in our master 2-DE protein database for normal human colon
      crypts and several colon carcinoma cell lines (URL address:
      http:(/)/www.ludwig.edu.au). Under reducing 2-DE conditions, the A33 antigen
      electrophoresis as 6 differentially charged isoforms (pI 4.6-4.8) with a single
      molecular weight species at M(r) approximately 55000.

PMID- 9150951
TI  - The different expression of proteins recognized by monoclonal anti-heat shock
      protein 70 (hsp70) antibody in human colonic diseases.
AB  - Analysis of the expression of hsp70 (70 kDa heat-shock proteins) in normal and
      pathological tissues might prove their potential diagnostic and prognostic
      values. In the present study, we combined high-resolution two-dimensional
      polyacrylamide gel electrophoresis with immunoblotting to study hsp70 expression
      in normal, preneoplastic and neoplastic colonic mucosa. By monoclonal anti-hsp70
      antibody, recognizing both the constitutive and inducible forms of hsp70, we have
      detected six charge isoforms localized in the pH 5.1-5.3 range and in the
      molecular mass range of 68-69 kDa in normal colonic mucosa. Immunostaining of
      hsp70 in polypous and malignant tissues revealed qualitative as well as
      quantitative changes in the expression of more acidic isoforms of hsp70 in
      comparison with normal tissue. Furthermore, the different basic isoforms of hsp70
      were detected in chronically inflamed colonic mucosa from patients suffering from
      ulcerative colitis (UC) or Crohn's disease (CD). Besides the standard hsp70
      protein pattern, additional proteins with molecular masses of about 39, 40, 74
      and 75 kDa were variably immunostained in normal and pathological specimens.
      These observations suggest that hsp70 expression may be closely linked to disease
      etiology and/or pathophysiology.

PMID- 9150952
TI  - Protein expression changes associated with radiation-induced neoplastic
      progression of human prostate epithelial cells.
AB  - Carcinogenic progression in most epithelial systems is a multistep process and
      presents as numerous (un)stable intermediate stages prior to the development of a
      fully malignant phenotype. Recently, we reported the neoplastic transformation of
      an SV40 immortalized, neonatal human prostate epithelial cell line (267B1) by
      multiple exposures to X-rays [1, 2]. The parental 267B1 cells acquired anchorage
      independence and exhibited morphological transformation following exposure to two
      consecutive doses of 2 Gy. Exposure of either the parental 267B1 cells or the
      anchorage-independent derivatives (F3-SAC) to a total dose of 30 Gy of X-rays
      yielded tumorigenic transformants (267B1-XR and 267B1-SXR, respectively). All of
      these radiation-treated derivatives (F3-SAC, 267B1-XR, and 267B1-SXR) were
      characterized by reduced cell size and poorly organized actin stress fibers [2,
      3]. The present study examines the protein expression changes associated with
      cytoskeletal alterations during the different steps of neoplastic progression
      induced by X-rays in the in vitro human prostate cell system. This analysis was
      achieved by using the high resolving power of two-dimensional polyacrylamide gel
      electrophoresis (2-D PAGE) in the 267B1, F3-SAC, 267B1-XR, and 267B1-SXR cells.
      We report changes in the expression of gelsolin in the partially transformed,
      anchorage-independent, nontumorigenic (F3-SAC) cells and a progressive loss of
      expression of tropomyosin isoforms (TM-1 and TM-3), and myosin light chain-2 (MLC
      2) in the tumorigenic (267B1-XR; 267B1-SXR) cells, respectively. In contrast, our
      results demonstrate that the levels of the small GTP-binding protein Rho-A, an
      active participant in the actin stress fiber organization, are not altered during
      neoplastic progression of these 267B1 cells. Thus the changes in synthesis of
      gelsolin, tropomyosins, and MLC-2 provide a rationale for the alterations in the
      actin stress fiber formation and reduction in cell size during the exposure of
      prostate epithelial cells to multiple doses of X-rays.

PMID- 9150954
TI  - Two-dimensional electrophoresis of precision-cut testis slices: toxicologic
      application.
AB  - Advances in tissue slice technology and a recent novel application of this
      technique to reproductive toxicology using bovine testis have demonstrated the
      remarkable utility of this approach. The objective of the present study was to
      combine this in vitro toxicity test system with large-scale two-dimensional
      polyacrylamide gel electrophoresis (2-DE) to detect and study alterations in
      testicular-slice protein patterns as molecular correlates of 1,3,5
      trinitrobenzene (TNB) and 1,3-dinitrobenzene (DNB) toxicity. Previous studies
      have shown that testicular slices remain viable for > 24 h and, as measured by
      protein synthesis inhibition, TNB causes dose-related injury. Tissue-slices were
      prepared from bovine testicles incubated for 2, 4 or 6 h and exposed to either
      100 microM, 500 microM or 1 mM DNB or TNB in the incubation medium. Slices were
      collected, solubilized, and separated by large scale 2-DE. Resulting protein
      patterns were then examined by image analysis, which revealed coefficients of
      variation in protein spot abundance comparable to patterns from fresh rodent
      tissue samples. Furthermore, specific protein alterations indicated dose-related
      inductions and declines in protein abundance, some progressive over time. The
      results of this investigation demonstrate the potential toxicologic utility of
      combining in vitro tissue-slice technology with high-resolution 2-DE protein
      mapping. The consolidation of these methods offers a novel approach for toxicity
      screening and testing, reduces experimental cost, and reduces the use of
      laboratory animals.

PMID- 9150953
TI  - Simultaneous analysis of cyclin and oncogene expression using multiple monoclonal
      antibody immunoblots.
AB  - Cell dysfunction or dysregulation in cancer generally results from complex gene
      interactions, numerous cellular events and environmental influences which modify
      gene expression or post-translational protein modifications. Genetic analysis in
      itself cannot always predict or diagnose multigenic diseases. The major technical
      difficulty is thus to detect, identify and measure simultaneously the expression
      of several genes and the post-translational modifications of their products. In
      order to progress to this direction, this paper describes a simple immunoblot
      method using several monoclonal anti-bodies to simultaneously analyze oncogene
      expression and cell cycle specific checkpoints in patient solid biopsies and
      transformed cell lines. One mg of normal human liver biopsy and HEPG2
      (hepatoblastoma-derived cell line) protein samples have been separated by two
      dimensional polyacrylamide gel electrophoresis (2-D PAGE) and transferred onto
      polyvinylidene difluoride (PVDF) membranes. The membranes were stained with amido
      black, scanned and tested separately with the nine monoclonal antibodies p53, c
      myc, PCNA, MEK1, pan-ras, Cip1, Cdc2, Kip1, and TCTP. The nine antibodies of
      interest were then combined to form a mixture, and simultaneously used as the
      primary antibodies. This antibody mixture simultaneously detected the nine
      proteins of interest on both samples and it demonstrated the extensive expression
      changes and the presence of various isoforms most likely due to post
      translational modifications of gene products.

PMID- 9150955
TI  - A protein expression database for the molecular pharmacology of cancer.
AB  - In the last six years, the Developmental Therapeutics Program (DTP) of the US
      National Cancer Institute (NCI) has screened over 60,000 chemical compounds and a
      larger number of natural product extracts for their ability to inhibit growth of
      60 different cancer cell lines representing different organs of origin. Whereas
      inhibition of the growth of one cancer cell type gives no information on drug
      specificity, the relative growth inhibitory activities against 60 different cells
      constitute patterns that encode detailed information on mechanisms of action and
      resistance (as reviewed in Boyd and Paull, Drug Devel. Res. 1995, 34, 19-109 and
      Weinstein et al., Science 1997, 275, 343-349). In order to correlate the patterns
      of activity with properties of the cells, we and other laboratories are
      characterizing the cells with respect to a large number of factors at the DNA,
      mRNA, and protein levels. As part of that effort, we have developed a two
      dimensional gel electrophoresis (2-DE) protein expression database covering all
      60 cell types (Buolamwini et al., submitted). Here we present analyses of the
      correlations among protein spots (i) in terms of their patterns of expression and
      (ii) in terms of their apparent relationships to the pharmacology of a set of
      3989 screened compounds. The correlations tend to be stronger for the latter than
      for the former, suggesting that the spots have more robust signatures in terms of
      the pharmacology than in terms of expression levels. Links to pertinent databases
      and tools of analysis will be updated progressively at
      http:@www.nci.nih.gov/intra/lmp/jnwbio.htm and
      http:@epnwsl.ncifcrf.gov:2345/dis3d/dtp.++ +html.

PMID- 9150956
TI  - Construction of a directory of tobacco plasma membrane proteins by combined two
      dimensional gel electrophoresis and protein sequencing.
AB  - The polypeptide pattern of the plasma membrane from tobacco was studied by two
      dimensional gel electrophoresis. When using classical carrier ampholyte
      isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (IEF/SDS-PAGE) approximately 400 polypeptide spots were detected after silver
      staining and computer analysis using the QUEST software. This resolution was
      sufficient to assess physiological effects such as changes in a phytohormone
      concentration. By using pH 4-8 immobilized pH gradient (IPG)-IEF and 10%T SDS
      PAGE gels, approximately 600 polypeptides, corresponding to ca. 80% of the total
      population expected, were resolved. This cross-section of the plasma membrane
      polypeptide population was mainly constituted by low or intermediate molecular
      mass (25 to 45 kDa) and acidic (5.2 < pI < 6.1) polypeptides. After sample
      application by in-gel rehydration, large amounts of plasma membrane protein
      (between 5 mg and 10 mg protein) were analyzed using IPG-IEF, and N-terminal
      protein sequencing was performed for polypeptides collected from one gel.
      Internal protein sequences were also obtained. Nearly all protein sequences
      corresponded to unidentified proteins but several of them matched translated
      sequences from unidentified plant expressed sequence tags (ESTs). It is concluded
      that the combined use of IPG-IEF gels and in-gel rehydration allows, in the case
      of plant membrane protein, both analytical and micropreparative separations with
      an efficiency comparable to that demonstrated for soluble proteins. Finally, it
      is suggested that a systematic investigation of plant plasma membrane
      polypeptides is feasible and would constitute a source of new and plant-specific
      genes.

PMID- 9150957
TI  - Clinical studies of the vibration syndrome using a cold stress test measuring
      finger temperature.
AB  - Since nine years multicentre, transversal and longitudinal clinical studies on
      hand-arm, vibration-exposed patients are being performed in cooperation with
      French occupational medicine centers and social security institutions. These
      studies are based upon current clinical assessment and standardized, temperature
      measuring cooling tests. Data acquisition uses a portable, 10-channel, micro
      processor-based temperature recorder and miniature thermal sensors. Temperature
      is monitored at the ten finger tips continuously, before, during and after a cold
      stress performed in strictly controlled conditions. Data from examinations
      performed at outlying sites are transferred through the telephonic network to a
      central processing unit. Data analysis uses a specific, expert-type software
      procedure based upon previous clinical studies on (i) 238 "normal" subjects, and
      (ii) 3,046 patients with vascular disturbances of the upper extremities of
      various etiologies. This procedure includes a staging process which assigns each
      finger a class representing the degree of severity of the abnormalities of
      response to cold ("dysthermia") related to vascular disorders. All data
      processing is fully automatic and results in a printed examination report. To
      date, over 1,623 vibration-exposed forestry, building and mechanical workers were
      examined. Sixty-three per cent of patients had received high dose of vibration
      (daily use of chain saws, air hammers, ballast tampers over many years). Typical
      white finger attacks or only neurological symptoms were found in 36% and 23% of
      patients respectively. The rate of sever dysthermia was much higher in patients
      with white finger attacks (83%) than in patients without (32%). In 90% of the
      vibration-exposed patients, the severity of dysthermia has differed greatly from
      one finger to another and between hands, while in non-exposed patients with
      primary Raynaud syndrome the dysthermia are generally similar for all fingers but
      the thumbs. Of 208 forestry workers who were asymptomatic but had dysthermia on a
      first examination, 31% have developed vascular or neural symptoms within
      subsequent follow-up. Of 223 symptomatic patients with more or less severe
      dysthermia at a first examination performed in winter, 17% had the same
      abnormalities in summer and microvascular lesions at capillaroscopy, while the
      other 83% had reversible dysthermia and only functional capillaroscopic
      abnormalities. These studies suggest that temperature-measuring cooling tests
      performed under well-defined, standard conditions provide significant data for
      grading the severity and assessing the reversibility of Raynaud phenomena, and
      for detecting subclinical vasomotor disorders in asymptomatic patients.

PMID- 9150958
TI  - Vibration syndrome and autonomic nervous system.
AB  - It is well known that hand-arm vibration affects the hand and arm which are
      directly exposed to vibration. However, through the sympathetic nervous system,
      hand-arm vibration can affect the foot which is not directly exposed to
      vibration. Hand-arm vibration activates the sympathetic nervous system, and
      induces vasoconstriction in the four extremities. And patients with vibration
      syndrome have circulatory disturbances of the foot as well; some patients had
      Raynaud's phenomenon of both fingers and toes, those with VWF were likely to
      complain of coldness in the feet as well as the hands, and had low skin
      temperature of the fingers and toes. In addition, arterial pathological changes
      like medial muscular hypertrophy have been observed in both fingers and toes of
      the patients. Prolonged repeated vasoconstriction of the foot induced by hand-arm
      vibration through the sympathetic nervous system is supposed to result in
      arterial changes like medial muscular hypertrophy in the foot and eventually
      circulatory disturbances of the feet. Hyperactivity of the sympathetic nervous
      system to cold, which is shown in patients with VWF, also probably contributes to
      the foot disturbances. The effect of hand-arm vibration through the sympathetic
      nervous system should be considered in hand-arm vibration syndrome.

PMID- 9150959
TI  - Vascular responses to acute vibration in the fingers of normal subjects.
AB  - The aim of this experimental study was to investigate the pathophysiological
      mechanisms involved in the acute effects of unilateral vibration on the digital
      circulation of healthy men. In the fingers of both hands of eight male subjects
      (age 23-47 years) who had never worked with vibrating tools, finger blood flow
      (FBF) and finger skin temperature (FST) in thermoneutral conditions, and the
      percentage change of finger systolic pressure (FSP %) after local cooling from 30
      to 10 degrees C were measured. The right hand was exposed for 30 min to
      sinusoidal vibration with a frequency of 125 Hz and an acceleration of 87.5 m.s.
      2r.m.s. A control condition consisted of exposure to the same static load (10 N)
      but without vibration. The measures of digital circulation were taken before
      exposure to vibration and static load and at 0, 30, 60, and 90 min after the end
      of each exposure. Exposure to static load caused no significant changes in FBF,
      FST, or FSP % in either the test right or the control left finger. Immediately
      after vibration, there was a temporary increase in FBF in the vibrated right
      finger, while the non-vibrated left finger exhibited no vasodilation. In both the
      vibrated and non-vibrated fingers, FBF and FST significantly reduced during the
      recovery time. A large inter-subject variability was observed for FBF and, to a
      lesser extent, for FST. In the vibrated right finger the decrease in blood flow
      was significantly related to cold-induced vasoconstriction in the digital
      vessels. Such a relation was not observed in the non-vibrated left finger. The
      results of this investigation suggest that acute vibration can disturb the
      function of digital vessels through two different and opposite mechanisms.
      Vibration appears to produce local vasodilation and to trigger a central
      sympathetic reflex vasoconstriction which can be recorded in the ipsilateral and
      the contralateral finger to vibration. Both local and central vasoconstrictor
      mechanisms are likely to be involved in the response to cold observed in the
      digital vessels of a vibrated finger.

PMID- 9150960
TI  - Experience on the reversibility of the vibration-induced white finger disease.
AB  - In connection with medical appraisements of the occupational disease No. 2104
      "Vibration-induced vasospastic disease" 240 patients could be examined a first
      time, 94 of them a second time, 42 patients a third time and 11 patients a forth
      time. The interval between examinations was 2, 4 or 6 years respectively. The
      standard procedure besides clinical whole body examination included anamnestic
      questionnaire, cold-provocation test with infrared thermography and vibrotactile
      perception test. The evaluation of the diagnoses in principle followed the
      Stockholm vascular V and sensorineural SN stages and was used to establish the
      grade of disability for compensation. The re-examinations after 2-6 years gave
      information on the development of the health status after cessation of vibration
      exposure. In only about 54% of all cases there was any improvement, in 39% the
      health status was unchanged, in 7% aggravated. It is obvious that the
      reversibility of the VWF if any needs many years abstaining from vibration
      exposure.

PMID- 9150961
TI  - Age-related evaluation of peripheral circulation of workers with vibration
      exposure.
AB  - This study was designed to clarify the age variation of the indices in the
      accelerated plethysmography (APG) for fingers and set the standard ageing curve.
      The indices of APG of workers with exposure to vibration were compared with those
      of the standard ageing curves. The subjects were 815 male workers, ranging in age
      from 18 to 66, without exposure to vibration and without history of hypertension,
      circulatory diseases or diabetes. Their indices of APG are used establishing the
      standard ageing curves. The workers occupationally exposed to hand-arm vibration
      were also the subjects to evaluate peripheral circulation of hand. The APG was
      measured on the index finger tip of his dominant side by an accelerated
      plethysmometer. The subjects were divided into age groups at intervals of 5
      years. In all age groups from 18 to 64 years, each index of APG showed an
      approximately normal distribution in a logarithmic scale. The mode of the
      distribution shifted to a lower value with increasing age. The standard ageing
      curves were drawn by calculating 25th, 50th and 75th percentiles by a
      nonparametric method for each group. Each index of the standard ageing curves
      dropped with increasing age. The significant age effect was slightly marked below
      30 years, but marked between 30 and 50 years. The indices of APG of workers with
      exposure to vibration were also compared with those of the standard ageing curve.
      The indices of -b/a and a/d of workers with exposure to vibration were
      deteriorated beyond physiological change. We established the standard ageing
      curves for APG for male men. The technique is good for the evaluation of
      peripheral circulation disorder of aged workers with occupational exposure to
      vibration.

PMID- 9150963
TI  - Application of Stockholm criteria to patients with hand-arm vibration syndrome in
      a follow-up study.
AB  - We applied Stockholm criterion to patients with hand-arm vibration syndrome
      (HAVS) for assessing the therapeutic effects in comparison with the criterion of
      the Ministry of Labour in Japan (MLJ). Forty male patients recognized as an
      occupational disease were examined in two times (mean interval periods 3.0
      years). The subjects were free from vibratory tasks during the mean period of 8.3
      years. The clinical examinations and some laboratory tests were conducted with
      the same procedures by the two same occupational physicians. The criterion of MLJ
      was graded more severe than Stockholm one for the vascular component at the first
      examination. According to Stockholm criterion, 16 patients (40%) were classified
      into stage 0 in the vascular component, 11 (70%) of which complained of coldness
      in the fingers. At the second examination, 9 of 16 patients in stage 0 had
      Raynaud's phenomenon (RP). On the other hand, the criterion of MLJ could reflect
      an improvement of symptoms, for example, coldness. The findings may indicate that
      Stockholm criterion for vascular component is not enough to assess the clinical
      changes for light stages according to the severity of RP alone. For the
      sensorineural (SN) component, both criteria were almost compatible. From the
      viewpoint of preventive medicine, it was concluded that Stockholm criterion was
      not suitable for evaluating their clinical severity in the early stage of HAVS.

PMID- 9150962
TI  - Involvement of endothelin in peripheral circulatory change induced by hand-arm
      vibration.
AB  - Physiologic mechanisms involving local vasoregulating factor, endothelium-derived
      relaxing factor (EDRF) and endothelium-derived constricting factors (EDCF) have
      been postulated to play a role in VWF. Recent evidence that endothelin is a
      potent vasoconstrictor peptide indicates that it may play a role in
      vasoregulation during vibration exposure through the local actions of EDRF or
      EDCF. Therefore, we examined the effects of grasping (50 N) and hand-arm
      vibration with an unweighted acceleration of 50 m/s2 rms at a frequency of 120 Hz
      in the direction of X-axis on digital blood flow (DBF) and on the level of plasma
      endothelin in 7 healthy male office workers. DBF was measured by an apparatus
      based on the thermal diffusion method where the thermal diffusion flow probe was
      incorporated in the Peltier's stack. In the grasping test, DBF decreased by about
      40% from resting level within 1 minute after the grasping was begun, and was
      maintained at almost the same level during grasping, but increased immediately
      after cessation of grasping. In the vibration exposure test, initial decrease in
      DBF due to grasping was the same as that observed in the grasping test, but DBF
      gradually increased when exposure to vibration was performed simultaneously. No
      significant change in plasma endothelin level was induced by grasping. Endothelin
      was significantly lower after exposure to vibration than at rest and after
      grasping. The grasping-induced decrease in DBF seemed to be due to mechanical
      compression of the vessels. The negative correlation between DBF and endothelin
      during vibration exposure suggests that a reduction in release of endothelin from
      smooth muscle into the vessel cavity during vibration leads to vasodilatation,
      possibly attributable to the local axon reflex.

PMID- 9150964
TI  - Re-evaluation of capillaroscopy of finger nailfold in vibration-exposed workers.
AB  - Two hundred and ninety-four vibration-exposed workers were examined for vibration
      disease (VD) for the worker's accident compensation. Most subjects were male.
      Their ages ranged from 24 to 68 years. Duration of vibration exposure ranged from
      3 to 30 years. After acclimatization at 25 degrees C to 27 degrees C for at least
      an hour, the nailfold capillaries of the ring (or middle) finger were studied
      with a light microscope. A cold water immersion test (5 degrees C, 10 min) was
      then performed. The morphological findings of the nailfold capillaries were
      classified based on the criteria by Fagrell & Lundberg. A hundred and eighty
      subjects were diagnosed as VD and 75 as non VD, even without taking the
      capillaroscopic findings into consideration. The classification of the
      capillarograms retrospectively investigated were as follows, i.e. in 98 VD
      subjects 40 cases were stage A, 42 stage B, and 16 cases stage C. In 26 nonVD
      subjects 13 cases were stage A, 10 stage B, and 3 cases stage C, respectively.
      When the borderline of VD and nonVD existed between stage A and stages B and C,
      the sensitivity was 59.2%, specificity was 50.0%, and false positive and negative
      were 50.0% and 40.8%. Relationship between the capillary stage and recovery (%)
      of the skin temperature during the cold water immersion test was also studied.
      The recovery in stage C was not always lower than that in stage A. Among them,
      arteriography was performed in 57 cases. Despite the use of vasodilator, markedly
      delayed perfusion of the finger tips was observed in 28 cases. Their capillary
      stages were A in 12 cases, B in 11 and C in 3. The peripheral microcirculatory
      state in VD should be carefully evaluated in combination with appropriately
      selected examinations, including finger nailfold capillaroscopy.

PMID- 9150965
TI  - A new criterion proposed for the diagnosis of hand-arm vibration syndrome.
AB  - To propose a new criterion for the diagnosis of hand-arm vibration syndrome
      (HAVS), we evaluated the severity of the patients in comparison with the
      criterion of the Ministry of Labour in Japan (MLJ) and the Stockholm criterion.
      The characteristics of the Stockholm criterion was to classify severe cases with
      vascular disorders, because of evaluation due to the frequency of Raynaud's
      phenomenon alone. The Stockholm criterion diagnosed the HAVS separately in
      vascular and sensorineural disorders. The MLJ criterion was able to subdivide
      light stages. In vascular disorders, the MLJ criterion made serious consideration
      about cold sensation which appeared long before the occurrence of Raynaud's
      phenomenon. The MLJ criterion diagnosed the patients with vascular, sensorineural
      and motor (musculoskeletal) system disorders comprehensively. A new criterion
      which we proposed includes sensorineural, vascular and motor system disorders,
      the grade of which is evaluated in each system. The diagnosis might be done
      comprehensively.

PMID- 9150967
TI  - The serum level of endothelin in patients with hand-arm vibration syndrome.
AB  - The authors discuss the relationship of serum concentrations of endothelin in
      patients with vascular disease due to vibration and the severity of the disease;
      the highest concentrations were found in the most advanced forms of disease.
      Combination of the vascular disease due to vibration with complicating
      cardiovascular diseases is also discussed. The authors prepared methodical norms
      for the elaboration and evaluation of the results of serum concentrations of
      endothelin. These norms are useful for comparing studies in various regions and
      for international cooperation. The paper presents preliminary results so far of
      small group of patients. The examination could be a useful additional method for
      the classification and assessment of severity and prognosis of the disease.

PMID- 9150966
TI  - High level of plasma thrombomodulin (TM) concentration and correlation with
      endothelin (ET)-1 in vibration-exposed patients.
AB  - We measured plasma level of TM and ET-1 in vibration exposed patients. The
      results showed the plasma level of TM in vibration exposed patients was
      significantly higher than in normal controls. The present findings showed
      relatively wide damage of endothelial cells in the vascular bed of vibration
      exposed patients. On the other hand, the mean level of ET-1 in these patients
      tended to be higher than in normal controls, though there was no difference.
      Further studies are necessary about the mechanism of endothelial damage in
      vibration syndrome patients and its contribution to peripheral circulatory
      disturbance of vibration syndrome including the role of ET-1.

PMID- 9150968
TI  - Finger systolic blood pressures: effects of cold provocation on the reference
      finger.
AB  - Finger systolic blood pressure measured after cold provocation and ischemia of a
      digit is used to assist in the diagnosis of vibration-induced white finger, VWF.
      A reduction in finger systolic blood pressure after cooling is assumed to
      indicate vascular dysfunction. The percentage pressure change observed in the
      tested finger is often corrected for whole body effects (systemic systolic
      pressure changes) according to the pressure change measured in a reference
      finger. The commonly used method of correction is based on assumptions as to the
      causes of any changes occurring in the reference finger. It is assumed that the
      reference finger is not differentially susceptible to the cold provocation of the
      test finger, arising from either close proximity to the cold provocation or from
      a vascular disorder in the reference finger. An experiment has been undertaken to
      investigate the repeatability, over three days, of measurements of the arm
      systolic pressures of both arms and the finger systolic pressures in air of four
      fingers of both hands. The systolic pressures of both arms and of four fingers of
      one hand were also measured whilst the fifth finger of the same hand was
      subjected to cold provocation at 10 degrees C. Twelve healthy male subjects were
      rested in a supine position for 15 minutes in a room at 21-24 degrees C before
      measurements were taken. Finger systolic blood pressures were recorded using
      strain gauge plethysmography. The results show that the systolic blood pressure
      measurements were generally repeatable, but differed with measurement location.
      Cold provocation of the test finger had little consistent effect on the systolic
      pressures measured at other locations. The results are interpreted with regard to
      the correction of finger systolic pressure using a reference measurement.

PMID- 9150969
TI  - The use of PSSD testing in comparison to vibrotactile testing of vibration
      exposed workers.
AB  - With the acceptance of the Stockholm scale for the neurological effects of Hand
      Arm. Vibration Syndrome, there has been increasing interest in selection of the
      appropriate screening and diagnostic procedures for worker evaluation. With the
      increased attention to worker surveillance to decrease morbidity, workers
      compensation and legal liability, a system that provides early detection as well
      as diagnostic specificity would be desirable. Up to now, most screening tests
      have suffered from lack of specificity or are time consuming in administration.
      Most diagnostic tests are too expensive or impractical to use on a screening
      basis. The Pressure Sensitive Sensory Device (PSSD) system with a modification of
      the two point discrimination system has been shown to be at least as effective in
      comparison to vibrotactile testing as well as less time consuming. In addition,
      the study shows that there is a favorable correlation between PSSD and nerve
      conduction studies. This system offers and effective method of evaluation of
      workers for the effects of Hand-Arm Vibration Syndrome as well as other
      ergonomically induced conditions such as Carpal Tunnel Syndrome. Studies of
      various population groups will be presented.

PMID- 9150970
TI  - Digital nerve conduction velocity for evaluation of peripheral nerve impairments
      in vibration syndrome.
AB  - In order to evaluate peripheral nerve impairments in vibration syndrome, sensory
      nerve conduction velocity (SCV) in the digital segment of the median nerve was
      measured by applying electrical stimulation to the wrist and recording from two
      pairs of electrodes attached to the middle finger. Fractionated SCVs were also
      measured in the palm-to-finger, wrist-to-palm, and elbow-to-wrist segments of the
      median nerve. Subjects were 65 patients with vibration syndrome and 48 healthy
      controls of similar age. SCVs in the digital nerve segment were significantly
      slower in the patients than in the controls. Significant slowing was also found
      in the wrist-to-palm segment. SCVs in the palm-to-finger and elbow-to-wrist
      segments did not differ between the two groups. Slowed SCVs were most frequently
      encountered in the digital segment (38% of the patients). The slowing in the
      wrist-to-palm segment was found in 20% of the patients. Present findings indicate
      that the digital segment is most frequently affected in vibration-induced
      neuropathy, and measurement of SCVs in the digital segment would serve to
      evaluate the peripheral neuropathy in vibration syndrome.

PMID- 9150972
TI  - The growth and recovery of vibrotactile TTs caused by hand-transmitted repetitive
      shocks of various waveforms.
AB  - The effect of shock repetition rate on the temporary threshold shifts (TTSs) in
      vibrotactile perception at the fingers has been studied with shocks having
      exponential decays and hanning waveforms. The repetition rate of shocks delivered
      at the hand varied from 2 shocks per second up to 64 shocks per second. Subjects
      were exposed to vertical hand-transmitted repetitive shock vibration of equal
      energy contents. The magnitudes of the stimuli were adjusted to 2.8 ms-2 r.m.s.
      so that they were all equally severe according to current standards for assessing
      the severity of hand-transmitted vibration (e.g. International Standard 5349,
      1986). It was found that the TTS in vibrotactile perception decreased with
      decreasing shock repetition rate for both waveforms. The relation between the
      TTS, the logarithm of exposure time, and the logarithm of the ratio between the
      frequency-weighted r.m.s. acceleration and the peak amplitude was described by
      the relation TTS = 16.1 + 3.9log10T + 17.9log10 (RMS/PEAK), where TTS is the
      temporary threshold shift (in decibels), T is the exposure time, and RMS is the
      frequency-weighted r.m.s. acceleration according to BS 6842 and ISO 5349, and
      PEAK is the peak amplitude of the frequency-weighted acceleration. This shows
      that current standards are not appropriate for the prediction of the changes in
      vibrotactile perception produced by shocks such as those on many hand-held
      percussive tools.

PMID- 9150971
TI  - Response to psychological stressors in hand-arm vibration syndrome patients.
AB  - We investigated urinary catecholamines' response to acute psychological stress
      test in hand-arm vibration syndrome patients. Thirteen patients with vibration
      induced white finger (VWF) in higher frequency of attack, 7 patients with VWF in
      lower frequency, 6 patients without VWF and 17 healthy subjects were examined.
      All subjects were male and their average age (SD) was 59.2 (6.4), 56.3 (2.9),
      58.2 (4.7) and 56.8 (4.9), respectively. After an initial rest for 1 hour, acute
      psychological stress test with stressors--mirror drawing, watching horror video
      and arithmetic under intermittent noise was performed for 1 hour. Subjective
      complaints to the stress test were greater in patients with hand-arm vibration
      syndrome than in the healthy controls. The patient group with VWF in higher
      frequency indicated significant increases of urinary catecholamines (p < 0.05);
      average values (SD) at rest period and at stress test were 2.42 (1.17) and 3.71
      (1.82) micrograms/h for norepinephrine, and 1.47 (0.73) and 2.66 (1.79)
      micrograms/h for epinephrine, respectively. Increasing tendency of urinary
      catecholamines was observed in other three groups, however, they were not
      statistically significant. The sympathoadrenal medullary response to
      psychological stressors increased especially in hand-arm vibration syndrome
      patients with VWF in higher frequency.

PMID- 9150973
TI  - Vibrotactile perception sensitivity and its relation to hand-arm vibration
      exposure.
AB  - Vibrotactile perception thresholds (VPT) at seven test frequencies (8-500 Hz)
      have been measured and evaluated among 170 male employees at a heavy engineering
      production workshop, 125 of them were at present, or in the past, exposed to hand
      arm vibration. All participants were examined by a physician and none had
      symptoms of diseases or were exposed to other factors known to cause sensory
      neuropathies. VPTs [for the three lowest (8-32 Hz; non-Pacinian), for the four
      highest (63-500 Hz; Pacinian) and for all test frequencies together] and a
      sensitivity index (SI) has been individually graded in four (normal, slightly
      deteriorated, deteriorated and seriously deteriorated) and two (normal, abnormal)
      stages, respectively, and put in relation to individual exposure of vibration.
      The results do not show any clear relationship on an individual basis between
      vibration exposure and degraded vibrotactile perception. On a group basis,
      however, there is a clear tendency towards detoriorated VPTs when the study group
      is divided in exposure categories. The detorioration is most pronounced in the
      frequency range mediated by Pacinian corpuscles. In this range an approximately
      four-fold increase of relative risk for elevated VPT for those in the highest
      exposure category was observed compared to the non-exposed group. Corresponding
      relative risk estimate for SI is about 6. Therefore, the results suggest an
      existence of an exposure-response relationship.

PMID- 9150974
TI  - Temperature and vibration perception thresholds in workers exposed to hand-arm
      vibration.
AB  - Exposure to hand-arm vibration causes damage in the peripheral nerves of the
      upper extremities, and a method for early detection of neuropathy induced by
      vibration is needed. The thin nerve fibres seem to be the most sensitive to
      vibration and may be damaged first. In the present study, vibration and thermal
      thresholds in workers exposed to hand-arm vibration were compared in a case
      control study. Previously, both vibration perception and temperature sense have
      been impaired in workers exposed to hand-arm vibration. The study population
      consisted of 15 workers exposed to hand-arm vibration (mean age 37.1 yrs) and 15
      controls matched for age (mean age 36.1 yrs). The vibration perception thresholds
      (VPT) were measured with modified Bruel & Kjaer's equipment with the limits
      technique method. Thermal sense was measured by the Marstock method with a
      thermostimulator, in which the Peltier element controls the temperature of a thin
      metal plate (surface 35 x 40 mm) in contact with the skin. The lumberjacks had
      lower cold thresholds and wider neutral zones of temperature sensation in the
      hands and slightly higher VPTs at the high frequencies (125-500 Hz) than the
      controls. The results for the matched pairs showed 80-87% of the lumberjacks to
      have wider neutral zones, but only 53-66% of them had higher VPTs than the
      controls. In an intraindividual comparison of the lumberjacks (the newly scaled
      results with the mean and standard deviation of the controls), the temperature
      sense was often (66-73%) deteriorated more than the VPTs at 125-500 Hz. In
      addition, the newly scaled results showed the width of the neutral zone to be
      significantly more deteriorated than the VPTs at 125 and 250 Hz in the fingers.
      This indicates that measurement of the temperature sense is useful in the
      prevention of nerve damage caused by vibration and might be more sensitive to
      vibration than vibration perception.

PMID- 9150975
TI  - Assessment of heat pain perception in relation to vibration exposure.
AB  - The effect of vibration on thin unmyelinated sensory fibers was studied by
      perception threshold measurement of heat pain. The investigation was a cross
      sectional study of 98 vibration-exposed and 53 non-vibration-exposed workers.
      Pain perception was determined by using the "Marstock" method. The perception
      threshold of contact heat induced pain was assessed by the method of limits.
      Quantified personal energy-equivalent vibration exposure was assessed for all
      subjects on a group basis. The cumulated lifetime equivalent frequency-weighted
      vibration exposure was estimated based on measurements according to ISO 5349. The
      mean heat perception threshold was 46.2 degrees C (SD 2.6 degrees C) for the
      right hand and 46.0 degrees C (SD 2.7 degrees C) for the left. The results showed
      no mean difference (left = 0.1 degree C, right = 0.6 degree C) in heat pain
      perception between vibration-exposed and non-exposed subjects. There was a high
      correlation between the right and left hand measurements (r = 0.81). The risk
      (rate ratio) for impairment was 1.02 (95% CI 0.81-1.30) for the right hand and
      1.00 (95% CI 0.79-1.26) for the left. The results of the study did not indicate
      any impairment as assessed by an increased perception threshold for heat pain.
      The lack of an increased heat pain threshold among the vibration-exposed workers
      in our study cannot exclude a possible lesional somatosensory influence from the
      exposure, as the lesional effect may also be a lowering of the threshold. The
      multiple and unrelated percepts of thermal sensations imply that it is not
      legitimate to draw conclusions about the total status of the small calibre
      afferents when testing only the heat pain perception.

PMID- 9150976
TI  - Investigations of the suitability of pallesthesiometry in the diagnostics of
      functional disturbances of the peripheral nervous system.
AB  - This contribution presents the results of fundamental investigations of the
      suitability of measurements of vibration sensitivity threshold
      (pallesthesiometry) as a method for the assessment of vibration-induced nerve
      impairments. Sinusoidal vibration stimuli are applied at the fingertips of the
      subjects in this method. The sensitivity threshold of the subjects is determined
      similar like the hearing threshold in audiometry and is used as a measure for
      possibly existing nerve disorders. Laboratory and field experiments were carried
      out by means of a simple to serve and inexpensive pallesthesiometer. The test
      results proved the suitability of the pallesthesiometry for screening purposes in
      principle. Concentration and cooperation of the subjects as well as the suitable
      selection of the investigation frequencies according to the frequency content of
      the vibration exposure are of essential meaning for comparable and reliable
      measuring results. Furthermore the rest and vibration-free position of the hand
      and fingers during the measurement of the thresholds are important to avoid
      measurement falsifications. A most extensive standardization of the investigation
      methodology and of the measuring equipment as well as the establishment of
      normative values of the sensitivity thresholds for different age groups are
      necessary for a broad application of the pallesthesiometry in practice.

PMID- 9150977
TI  - Nerve conduction velocities in the lower extremities among patients with
      vibration syndrome.
AB  - In order to clarify the effect of vibration syndrome (VS) on the peripheral
      nervous system (PNS) in the lower extremities, 59 patients with VS (age 58.5 +/-
      5.1 years) and 49 age-matched controls (age 57.0 +/- 5.1 years) were examined for
      sensory nerve conduction velocities (SCV) in the sural nerve (SSCV) and the
      medial plantar nerve (PSCV) in the summer of 1993 and 1994. They had not been
      suffering from diseases and injuries which might have affected the SCV in the
      lower extremities. These patients were divided into two subgroups, one with past
      vibration exposure to chainsaw (N = 22) and the other with past vibration
      exposure to rock drills and other tools (N = 37). SCVs corrected by skin
      temperature were subjected to statistical analysis. In PSCV a significant
      reduction among all patients (40.8 +/- 4.24 m/s, p < 0.01) including two
      subgroups (chainsaw, 39.7 +/- 4.7 m/s, p < 0.01; rock drill and others, 41.0 +/-
      4.6 m/s, p < 0.01) was observed compared with those of the controls (43.2 +/-
      4.31 m/s), but there was no significant reduction in SSCV. Significantly more
      subjects with PSCV below the standard of PSCV (ten percentile value of those of
      the controls) were observed among all patients (17/59, 28.8%, p < 0.05) including
      two subgroups (chainsaw, 7/22, 31.8%, p < 0.05; rock drill and others, 10/37,
      27.0%, p < 0.05) than in the controls (4/49, 8.2%). These findings suggested that
      VS affected the PNS function in the lower extremities and that its mechanism was
      considered to mediate a circulatory disturbance, and to differ from SCV reduction
      in the finger.

PMID- 9150978
TI  - Effect of starting temperature on the repeatability of thermotactile thresholds.
AB  - Hand-transmitted vibration has been observed to cause a wide variety of different
      signs and symptoms of neurological dysfunction. Different tests of tactile
      sensitivity, encompassing sensations of pressure, vibration, pain and temperature
      have been employed in the quantification of the sensorineural effects of
      vibration. However, since the results of such tests are dependent on different
      variables, and different versions of each test are used in different
      laboratories, the results are rarely reported in a manner allowing a direct
      comparison of results between studies. This paper reports on an investigation of
      the repeatability of thermotactile thresholds, as used in the detection of some
      neurological effects of hand-transmitted vibration. In the test, the temperature
      of a surface increased or decreased from a fixed reference (i.e. starting)
      temperature at a rate of 1 degree C per second. In a group of 10 health male
      subjects, five measures of both warm and cool thermal thresholds were obtained
      with each of 5 different starting temperatures on each of 3 different days. The
      'neutral zone' between the warm and cool thresholds was also calculated. The
      starting temperature was found to have a significant effect on warm and cool
      thresholds, and less effect on the width of the neutral zone. It is concluded
      that the starting temperature should be controlled when determining thermotactile
      thresholds.

PMID- 9150979
TI  - The vibrotactile threshold (VT) at the fingertips of chain saw operators.
AB  - The vibration sensitivity of the skin at the ten fingertips was tested with 72
      chain saw operators examined due to VWF-disease and compared with controls. The
      vibrotactile perception threshold (frequency f = 125 Hz, load p = 1.3 N) proved
      to be 3 to 5 times as high for the exposed group compared to controls. There was
      no correlation between vibration sensitivity and peripheral circulation found in
      cold provocation test. Two different testing instruments (pallaesthesiometer =
      vibrotactometer) showed significant differences in results probably due to
      different technical details of the methods. It may be concluded that a
      standardization of the instrumentation and method is necessary for testing the
      vibrotactile perception threshold as a part of the nervous function in a
      comparable manner.

PMID- 9150980
TI  - Effect of impulse vibration and noise on vasomotor function of peripheral blood
      vessels among pneumatic forge hammer operators.
AB  - An evaluation of the effect of impulse vibration and noise on vasomotor function
      of blood vessels among pneumatic forge hammer operators has been presented based
      on thermal tests (cooling). The study covered the following groups of workers;
      pneumatic forge hammer operators (I), pneumatic forging hammer operators (II),
      hammer operator's assistants (III), operators of forging presses and machines
      (IV) and the control group. The results of the study showed that in groups I and
      III it was impulse noise not vibration that caused changes in the functioning of
      peripheral blood vessels.

PMID- 9150981
TI  - Hand-arm vibration in tropical rain forestry workers.
AB  - Working conditions and health hazards including vibration syndrome related to
      forestry work using chain-saws were studied in Papua New Guinea and Indonesia.
      The subjects comprised 291 workers including 97 chain-saw operators. The health
      examination consisted of peripheral circulatory and sensory tests in the upper
      extremities. The vibration spectrum measured at the handle of the chain-saw
      indicated that these acceleration levels would lead to a moderately high risk of
      hand-arm vibration syndrome (HAVS). The peripheral circulatory function tests
      revealed dysfunction after more than five years vibration exposure. However, in
      general, the results of the function tests and subjective complaints showed fewer
      health problems compared to those of Japanese forestry workers. The reason of
      such differences of vibration effects seem to be the following: (1) warmer
      climate (more than 25 degrees C throughout the year), (2) young workers and short
      work experience. (3) short time vibration exposures on working days in the
      natural forests, (4) seasonal changes in logging work (5) healthy workers
      effects. Thus, we found no clear evidence that the workers of our study suffered
      from HAVS. A principal component analysis was applied. The factor score of the
      components of the reactive dynamics of peripheral circulation differed
      significantly after more than five years' exposure. On the other hand, we cannot
      deny the possibility that subclinical dysfunction of peripheral circulation may
      be caused by chain-saw operation in the tropics in future. Further investigations
      on the HAVS among forestry workers in the tropic environment are needed.

PMID- 9150982
TI  - Health status of the workers using mechanized hand tools in an electric parts'
      maker.
AB  - The aim was to clarify the relations between the health status of the workers
      operating mechanized hand tools (MT). MT included electric drivers and air
      drivers, and the working conditions in an electric parts' maker. Fifty-nine
      female workers underwent the special examination for vibration hazards, made up
      of 39 MT operators (Group A) and 20 controls (Group B) who worked without MT at
      the same plant. The authors made questions about their health and working
      conditions and physical examinations. The measured items of the peripheral
      nervous system were the vibratory sensation and sensory nerve conduction velocity
      (SNCV) in the hand and arm. Those of the musculoskeletal function were pinching
      power, grasping power, back strength, and tapping ability. The frequency of the
      complaints "tingling of hands" and "numbness of hands" and "difficulty of finger
      extension" in Group A was significantly higher than in Group B. The frequency of
      "swelling of hands" and "heavy feeling of arms" in Group A had a higher tendency
      than in Group B. There was no difference in the results of physical examinations
      and vibratory sensation. Pinching power and grasping power (both hands) and back
      strength in Group A was greater than in Group B. Median SNCV in the hand in Group
      A was significantly slower than in Group B. The maximum vibration acceleration
      level (0.56-1.8 m/s2) of the MT used at the plant did not exceed the exposure
      guideline of ISO. The results suggest that although the vibration level was low
      enough, physiological changes appeared in the workers with MT.

PMID- 9150983
TI  - Operating vibrating tools and prevalence of subjective complaints in vibration
      syndrome.
AB  - The aim of this paper is to evaluate the prevalence of subjective symptoms and
      signs related to vibration syndrome in various groups of subjects exposed to hand
      arm vibration (HAV). In 9 groups of subjects occupationally exposed to HAV, one
      group of subjects previously exposed to HAV, one control group, and 2 groups of
      general population (males and females), the prevalence of finger blanching,
      numbness in the hands, stiffness in the hands, and pain in the hands were
      investigated. The age of subjects ranged from 25 to 59 years. In subjects exposed
      to HAV, hand-transmitted vibration levels (HTVLs) were measured by means of
      vibration dosimeters, and the frequency-weighted acceleration levels [(Lh,w)eq,t]
      were determined as the vibration levels. The prevalence of vibration-induced
      white finger (VWF) in the exposed subjects was in the range of 0.0-9.6%, and that
      in subjects who were previously exposed to HAV was 4.1%. The prevalence rates of
      finger blanching in males and females of the general population were 2.7 and
      3.4%, respectively. The highest prevalence rate of VWF was observed among
      subjects exposed to HTVLs of 2.7-5.1 m/s2. The prevalence of numbness of the
      hands fluctuated among the groups; i.e., in the exposed groups: in the range of
      6.5-30.4%; in those previously exposed to HAV: 16.4%; and was 13.4% in males and
      29.5% in females of the general population. The prevalence rates of stiffness in
      the hands were in the range of 7.6-65.2% in the exposed workers, 13.7% in those
      previously exposed to HAV, and was 5.5% in males and 20.9% in females of the
      general population. The prevalence of pain in the hands was between 7.4 and 17.4%
      in the exposed groups, 1.4% in those who stopped exposure to vibration, and 1.2%
      in subjects without segmental vibration exposure. Among the subjective symptoms,
      only VWF showed a significant positive correlation with the measured vibration
      acceleration; Y = -0.9 + 1.9 X, r = 0.8, P = 0.01. It was concluded that VWF is
      the most appropriate signs in decisions concerning quantitative recommendations
      for segmental vibration exposure.

PMID- 9150984
TI  - Screening of vibration-induced disorders in the building industry using digital
      tactilometry. Results of a field study.
AB  - As occupational physicians in the building industry, we observed among these
      workers a high frequency of vibration exposure, during different tasks. We
      intended to study vibration exposure effects on vibration perception thresholds
      measured by digital tactilometry in this population of construction workers. A
      cross-sectional field study was made, 405 subjects were examined; each of them
      answered a questionnaire, underwent a medical examination and performed a test
      measuring his vibration perception thresholds, 150 subjects constituted the
      reference group. A close relationship between age and thresholds among the non
      exposed group was observed. A threshold normalization of age of study the 204
      exposed subjects was applied. Two exposure indices allowing time dependency
      vibration exposure analysis were defined the present daily exposure and cumulated
      exposure. In the examined population, thresholds rise with the present daily
      exposure in hours per day for 125 Hertz, while no significant influence of
      cumulated exposure is apparent. It was also pointed out that subjects exposed
      more than one and a half hour per day have higher thresholds than reference
      subjects, even if they do not have any clinical neurological complaints. This
      results seems to indicate the infraclinical feature of the test. These results
      suggest that screening of hand-arm vibration exposed population should be
      developed using this method. As occupational physicians in the construction
      industry, practising in Paris and surrounding areas, the authors studied the
      relationship between neurological disorders measured by vibrotactile perception
      thresholds, and hand-arm vibration exposure, among workers. They present the
      results of a field study they led within their institute, in collaboration with
      the tested workers' firms, and with the financial participation of the French
      Ministry of Labour.

PMID- 9150985
TI  - Results of independent medical interview and examination in the diagnosis and
      assessment of hand-arm vibration syndrome.
AB  - In the UK the use of the Stockholm Classification has been recommended by the
      Health and Safety Executive and by the Working Party of the Faculty of
      Occupational Medicine. The Stockholm Workshop 1994 did not recommend any changes
      to the existing classification but considered the variety of screening and
      diagnostic tests suitable for the staging of HAVS. Thirty one males claiming to
      be suffering from HAVS were interviewed and examined by each of the authors
      independently. The examination of each patient included detailed occupational and
      medical histories, standard physical examination with the additional tests of the
      rewarm time and aesthesiometry. Thermal neutral zone test (TNZ), vibrotactile
      thresholds and grip strength were also performed by McGeoch. All patients were
      classified by the Taylor/Pelmear and Stockholm Classifications. Both authors
      agreed that all the patients were suffering from HAVS. Agreement to within one
      stage was high for both the vascular and neurological elements. The additional
      neurological tests used by McGeoch appeared to result the raising of the
      neurological staging. The results indicate that independent interview plus
      objective tests performed by experienced physicians allow for reliable diagnosis
      and staging of claimants. Standardisation of tests is urgently required.

PMID- 9150986
TI  - Vibration syndrome in railway track maintenance workers.
AB  - An inquiry was sent to all railway maintenance workers in three railway districts
      in Finland and hand-arm vibration was measured on the handlebars of tools used by
      maintenance workers. The study group included 252 (82%) subjects, whose mean age
      was 41 years and who had worked in track maintenance for 14 years (SD 9). In
      Finland there are over 600 railway maintenance workers who use vibrating tools.
      The frequency-weighted acceleration of hand-arm vibration was calculated
      according to the ISO 5349 standard. Hand-held tamping machines had caused most of
      the vibration exposure, and aw4h was 10.6 m/s2 measured on the handlebar of
      tamping machine, but many workers also used other vibrating tools. The annual
      vibration level was 2.5 m/s2 when the use of all vibrating tools and the exposure
      time was taken into account. In the questionnaire the prevalence of vibration
      induced white finger (VWF) was 14% in the entire material, and the prevalence of
      VWF increased significantly with the total duration of the maintenance work. In
      addition, 39% of the subjects had suffered numbness of the hands, and the
      prevalence of hand numbness also increased significantly with the total duration
      of maintenance work. According to the measurements of vibration and the
      prevalence of hand symptoms the present investigation indicates vibration
      syndrome as being related to railway track maintenance work. In the exposure
      group, where tamping machines mainly were used and exposure to other vibration
      was small, the prevalence of VWF was also significantly higher, but the
      prevalence of hand numbness insignificant compared with the control group. In
      this study vascular and nerve hand symptoms were considered to cause serious
      trouble in work by 4-11% of the maintenance workers.

PMID- 9150987
TI  - Statistical analysis of vibration-induced bone and joint damages.
AB  - Vibration-induced damages to bones and joints are still occupational diseases
      with insufficient knowledge about causing and moderating factors and resulting
      damages. For a better understanding of these relationships also retrospective
      analyses of already acknowledged occupational diseases may be used. Already
      recorded detailed data for 203 in 1970 to 1979 acknowledged occupational diseases
      in the building industry and the building material industry of the GDR are the
      basis for the here described investigations. The data were gathered from the
      original documents of the occupational diseases and scaled in cooperation of an
      industrial engineer and an industrial physician. For the purposes of this
      investigations the data are to distinguish between data which describe the
      conditions of the work place (e.g. material, tools and posture), the exposure
      parameters (e.g. beginning of exposure and latency period) and the disease (e.g.
      anamnestical and radiological data). These data are treated for the use with
      sophisticated computerized statistical methods. The following analyses were
      carried out. Investigation of the connections between the several
      characteristics, which describe the occupational disease (health damages),
      including the comparison of the severity of the damages at the individual joints.
      Investigation of the side dependence of the damages. Investigation of the
      influence of the age at the beginning of the exposure and the age at the
      acknowledgement of the occupational disease and herewith of the exposure
      duration. Investigation of the effect of different occupational and exposure
      conditions.

PMID- 9150988
TI  - Low intensity vibration exposure in postmen.
AB  - The complaints of white fingers in postmen who had used motorbikes and had been
      exposed to low intensity vibration were studied. Their vibration exposure was
      found to be 1-3 m/s2 per day, four hour equivalent value of frequency weighted
      acceleration. The rate of white fingers among all subjects was 2.8%. The rate was
      related not only to vibration/cold exposure but also to age and delivery area
      locations. The major part of the white finger occurrence reported here was
      considered to be due to primary Raynaud's syndrome, and it seems safe to conclude
      that, a daily vibration exposure of up to 2.5-3 m/s2 (4 h equivalent value) has
      not caused white fingers in this population.

PMID- 9150989
TI  - Bone mineralization changes in saw operators.
AB  - In vibration disease the impact on bone and joint systems is considered to be the
      least frequent one. It includes a degenerative component, rare necrotic
      alteration and osteoporosis, together with cystic alterations, in the carpal
      bones. The authors concentrated only on osteoporosis in the proximal parts of
      upper extremities. They evaluated by X-rays of the thorax the extent of
      mineralization and, consequently, the osteoporosis of the clavicles. For that
      purpose they used the corticodiaphyseal Barnett-Nordin index (BNI). In a group of
      107 chain saw operators whose both upper extremities had been exposed to the
      impact of vibration exceeding the threshold limit while operating a chain saw, a
      statistically significant difference was established in the mineralization of
      clavicles. These findings contrasted with a control group of 107 healthy males
      who had never worked with vibrating equipment. The authors did not establish a
      statistically significant dependence of these changes on simultaneously diagnosed
      traumatic vasoneurosis and neuropathy. After the risk elimination of vibration
      the value of the BNI indicates the dynamics and the reversibility of the
      parameter under observation. These findings suggest that osteoporosis due to the
      impact of vibrations is by no means a rare phenomenon. It does not affect only
      the distal parts of the upper extremities. Similarly as angiological and
      neurological changes, osteoporosis tends towards spontaneous adjustment, once the
      risk of vibrations has been eliminated.

PMID- 9150991
TI  - Determination of "vibration emission values" for fastener driving tools
      (nailers).
AB  - Hand-held fastener driving tools (nailers, staplers, pinners) differ considerably
      from other vibrating tools in terms of mode of vibration. For satisfying the
      requirements of the Machinery Directive 89/392/EEC, including also the compulsory
      declaration of a characteristic vibration value, appropriate measuring methods
      had to be developed. The measuring method elaborated by the BIA and standardised
      under ISO 8662-11 takes into account existing regulations and, in particular,
      specifications applying to the standardised vibration measuring instrument. Apart
      from aspects related to measuring and working conditions, a particular problem
      consisted of excluding vibrations which are recorded although not generated by
      the tool. In addition, the use of vibration measuring instruments according to
      ISO 8041 was required, too. For these reasons a release cycle time was defined
      which is both a representative measure for the daily vibration dose and a
      compromise in terms of measuring accuracy. The paper presents first results
      obtained on the basis of the standard. It also gives an overview of the state of
      the art by indicating the load range as a function of the fastener size.

PMID- 9150990
TI  - Hand-arm vibration and terrain vehicles.
AB  - Hand-arm vibration was measured on the handlebars of terrain vehicles (N = 36)
      and a postal inquiry was made among N = 2705 reindeer herders (snowmobile
      drivers). Since many subjects had also used other vibrating tools the snowmobile
      group proper (N = 334) was established. In the whole group 19% of the subjects
      reported having experienced white finger attacks and 48% numbness of the hands.
      The frequency-weighted acceleration of snowmobile vibration was 3.5 m/s2, and
      risk evaluation using the ISO 5349 standard predicted the prevalence of white
      finger well in the snowmobile group proper. The vibration levels were 1.6-7.9
      m/s2 on snowmobiles, 5.5-11.8 m/s2 on all-terrain vehicles and 6.9-12.7 m/s2 on
      terrain motorcycles. The most critical points for damping the vibration were the
      motor mounting and resonance in the steering yoke. There is need for health care,
      technical improvements, and other protection means to reduce the symptoms of
      vibration in driving terrain vehicles.

PMID- 9150992
TI  - State of health in dental technicians with regard to vibration exposure and
      overload of upper extremities.
AB  - The authors examined 120 dental technicians, 111 women, 9 men, of mean age 44.8
      years, mean duration of exposure 24.9 years. Cold water test, plethysmographic
      investigation, and EMG (in indicated persons), X-ray, neurological and orthopedic
      examinations were performed. Combination of exposure to vibration above the limit
      value, with overload of upper extremities, was proved by hygienic measurement.
      The most frequent subjective complaints included vertebral complaints (52.5%),
      paresthesiae in the hand fingers (47.4%) and pain in the joints of upper
      extremities (elbow 26.6%, shoulder 10.8%, wrist 6.6% and small joints of hand
      6.6%). Four workers reported history of white fingers, but the cold water test
      did not prove it. Deteriorated plethysmographic curve was in 11 cases only.
      Pathological motor conduction in nervus medianus was found (by EMG investigation)
      in 13 persons. Carpal tunnel syndrome was acknowledged in 4 individuals as an
      occupational disease. The results of these investigations show the hazard of
      dental technicians work and the necessity of improvement of their work
      conditions.

PMID- 9150994
TI  - PIMEX--an instructive way to study vibration exposure and work posture.
AB  - The PIMEX-method (PIcture-Mix-EXposure) involves measurement of exposure with a
      direct-reading instrument. The signal from the instrument is superimposed to the
      recording from a video camera to produce a video film which continuously shows
      the subject at work and how exposure varies. Application can be a physical factor
      such as vibration. We used this new method to study vibrations from hand held
      grinders. Using Bruel and Kjaer miniaturized accelerometer 4374 and vibration
      meter 2513 we measured vibrations at the grinders main and support handles. We
      studied different grinders at work on the metal surface as well as at idle speed.
      Workers posture such as arms in under-up position was evaluated. The PIMEX-method
      has been encouraging to show correlation between vibration exposure, work
      technique and different grinders.

PMID- 9150993
TI  - Diurnal rhythms of the neuroendocrine system in professional riveters with
      different constitutional types.
AB  - In our earlier investigations it have been shown that experimental vibration
      exposure causes different endocrine reactions in hypothalamo-pituitary
      adrenocortical (HPA) and hypothalamo-pituitary-gonadal (HPG) systems in men of
      different constitutional types. The present study was carried out to determine
      diurnal rhythms of HPA and HPG systems in professional male riveters during a
      working day under industrial conditions. The state of HPA and HPG systems was
      evaluated according to the concentration of hormones cortisol (Cort.) and
      testosterone (T) in saliva. Mixed saliva was collected without stimulation at
      7.00, 11.00, 15.00, 19.00 and 23.00 h. The concentration of hormones was
      determined by radio-immunoassay. Only healthy workers with a long working time
      under vibration exposure were chosen for participation in the investigation. The
      workers were divided into three groups of abdominal (A), muscular (M) and
      pectoral (P) somatotypes according to the antropometric signs (Bunaris
      classification, 1941). The results of investigating the HPA system have shown
      that usual diurnal rhythm of Cort, was observed in 60% of all cases. This rhythm
      is characterised by the maximum concentration of Cort, at 7.00 h with subsequent
      lowering during the day. In 10% of all cases we observed very low concentration
      of Cort, at 7.00 h and in 30% there was a significant increase of the level of
      Cort, at 15.00 and 19.00 h. Another change of diurnal rhythm was revealed in the
      HPG system. The diurnal rhythm of T completely corresponds to the rhythm of Cort.
      The accordance of T concentration to the diurnal rhythm we observed only in 27%
      of all cases. In 47% of all cases the increase of T took place at 15.00 and 19.00
      h and in 20% the "monotonous" curve of T concentration without any changes of
      rhythm and with a low concentration at 7.00 h was observed. We also revealed
      different distribution of A, M and P somatotypes in connection with various
      diurnal rhythms of hormone curves. The result allows us to suppose that
      constitutional dependence of changes of diurnal rhythm of HPA and HPG systems
      probably underlines the adaptive processes to long time vibration exposure.

PMID- 9150995
TI  - Treatment of vascular disease caused by vibration.
AB  - Vascular diseases caused by vibration are treated by different methods. We
      ourselves applied in our patients subcutaneous injections of hot-spring gas, per
      os prazosin (postsynaptic blocker of alpha-sympathetic receptors) which except
      for its vasodilatory effect improves the rheologic qualities of blood).
      Subcutaneous injections of hot-spring gas were administered to 31 males aged 32
      to 67 years (average 50.58 years) for 15 days, Prazosin VUFB to 12 males aged 33
      to 64 years (average 47.8 years) for 28 days and pentoxifylline (Agapurin SPOFA)
      to 20 males aged 29 to 69 years (average 46.35 years) for 28 days. Simultaneous
      nervous disease caused by vibration was present in 12 patients, articular
      affections caused by vibration in 10 patients, and disease of peripheral nerves
      and joints in 16 patients. The subjective complaints were influenced mostly by
      hotspring gas, the cold water test by prazosin, the skin temperature and
      plethysmogram by pentoxifylline. When evaluating the number of favourably
      influenced indicators pentoxifylline is the most successful. Tolerance of all
      three methods proved to be good.

PMID- 9150996
TI  - Consideration of grip and push forces for the assessment of vibration exposure.
AB  - There is much influence of the coupling forces between hand and grip of the
      vibrating tool on the measuring results as well as on the vibration effects on
      the hand-arm system. In a research project the effects of grip and push forces on
      acute responses of the hand-arm system under vibration conditions have been
      studied. Using these results of the biodynamic response, vibration perception
      threshold and subjective vibration sensation a bonus/malus system for a
      correction of the measured frequency-weighted r.m.s. acceleration was drafted, to
      assess the hand-arm vibration at the workplace: Since there is no difference
      between the acute effects of grip force and push force, so the forces have to be
      added and defined as coupling force Fcf. On the basis of this coupling force Fcf
      a correcting factor cF may be calculated. The factor amounts to 0.6 at Fcf = 20
      N, 1.0 at Fcf = 120 N and 1.1 at Fcf = 200 N. To correct the measured weighted
      r.m.s. acceleration ahwz (Fcf) depending on coupling forces the r.m.s.
      acceleration has to be multiplied with the correcting factor cF. The drafted
      procedure enables to assess vibration exposure depending on coupling forces in a
      standardized way.

PMID- 9150997
TI  - Evaluation of indoor air quality using the decibel concept. Part I--proposal of
      new units.
AB  - Weber-Fechner's law concerning the perception of sound by man with time expressed
      as a logarithmic function can also be used for the odour constituent used in the
      evaluation of indoor air quality in buildings. A new unit dB (odour) based on the
      concentration of Total Volatile Organic Compounds (TVOC) is proposed as it is
      currently the basis for determining the air change rate. On the Psycho-Physical
      Scale according to Yaglou, the weakest odour that can be detected by the human
      small sensors is equal to one and corresponds to the lower limit of percentage
      dissatisfaction (PD) of 5.8% and a threshold concentration (TVOC) of 50
      micrograms/m3-0 dB (odour). The upper limit is determined by the initial value of
      toxicity TVOC-25,000 micrograms/m3-135 dB (odour). Optimal values corresponding
      to PD = 20% (according to EUR 14449 EN) and admissible values corresponding to PD
      = 30% (see Table 3) are proposed, therefore the same values used to evaluate
      noise can be used to evaluate air quality and additionally the contribution of
      individual constituents (at present acoustic and odour) to the overall quality of
      the environment can be ascertained. The determination of the required volume of
      fresh air for ventilation and air-conditioning systems according to the new
      principles is the subject of the Part II of this paper.

PMID- 9150998
TI  - Evaluation of indoor air quality using the decibel concept. Part II-ventilation
      for acceptable indoor air quality.
AB  - Weber-Fechner's law concerning the perception of sound by man with time expressed
      as a logarithmic function can also be used for the odour constituent used in the
      evaluation of indoor air quality in buildings. A new unit dB (odour) based on the
      concentration of Total Volatile Organic Compounds (TVOC) is proposed as it is
      currently the basis for determining the air change rate. On the Psycho-Physical
      Scale according to Yaglou, the weakest odour that can be detected by the human
      smell sensors is equal to one and corresponds to the lower limit of percentage
      dissatisfaction (PD) of 5.8% and a threshold concentration (TVOC) of 50
      micrograms/m3-0 dB (odour). The upper limit is determined by the initial value of
      toxicity TVOC -25,000 micrograms/m3-135 dB (odour). Optimal values corresponding
      to PD = 20% (according to EUR 14449 EN) and admissible values corresponding to PD
      = 30% (see Part I of this paper) are proposed, therefore the same values used to
      evaluate noise can be used to evaluate air quality and additionally the
      contribution of individual constituents (at present acoustic and odour) to the
      overall quality of the environment can be ascertained.

PMID- 9151000
TI  - New serovars of plesiomonas shigelloides--1996.
AB  - Eight new 0 (91-98) and H (46-49) antigens are described. Their reference strains
      come from Czech Republic, Cuba and USA. The majority of reference strains are of
      human origin. Some of the new antigens have been found in other strains coming
      mostly from water.

PMID- 9150999
TI  - Success of an outpatient claudication group training program for patients with
      peripheral arterial occlusive disease (PAOD): the Tubingen model.
AB  - Active exercise therapy plays a decisive role in the prognosis for early forms of
      peripheral arterial occlusive disease (stages I and II). We present a model
      project for an outpatient claudication group which has proved successful in the
      active exercise therapy of early forms of arterial occlusive disease (PAOD). In
      addition to the training principles familiar from intensified, performance-keyed
      walking programs, a newly developed pedal ergometer was employed which makes
      controlled endurance training possible for this patient group. The distance
      patients were able to walk without pain increased significantly in 17 out of the
      26 patients taking part in the program. This clinical success was confirmed by an
      examination of arterial hemodynamics. The transformation of a theoretical concept
      into a functioning training program and the positive results achieved with it
      should encourage others to establish similar programs close to the patients'
      homes.

PMID- 9151001
TI  - Campylobacter spp. and Salmonella spp. in black-headed gulls (Larus ridibundus).
AB  - Cloacal examination of 41 juvenile black-headed gulls (Larus ridibundus) by
      cultivation demonstrated Campylobacter jejuni in 26 (63%) and Salmonella
      typhimurium in 21 (51%) of them. All the bird samples were collected in a
      breeding colony near the town Hodonin, South Moravia, Czech Republic in 1996.
      Twenty six Campylobacter isolates were tested for antibiotic and drug
      sensitivity: all were resistant to at least three agents (Penicillin, Tetracyclin
      and Sulfomethoxazol-trimethoprim) while all were sensitive to Augmentan,
      Cefotaxim, Ciprofloxacin, Erythromycin, Nitrofurantoin and Cephazidine. Four
      percent of isolates were resistant to Ampicillin and Nalidixic acid. Of the 21 S.
      typhimurium isolates tested, 33% were sensitive to all drugs assayed, proportions
      of the strains resistant to Sulfomethoxazol-trimethoprim, Tetracyclin and
      Streptomycin were 58%, 16% and 8%, respectively.

PMID- 9151002
TI  - Hospitalization for pneumonia in the Finnish working-age population.
AB  - The aim of this investigation was to describe the use of hospital services among
      the Finnish working-age population aged 15 to 64 years on account of pneumonia.
      The study was based on nationwide hospital discharge records maintained by the
      National Research and Development Centre for Welfare and Health. Pneumonia caused
      63,414 periods of hospital treatment and a total of 568,861 hospitalization days
      among working-age people in Finland from 1984 to 1993. The mean annual age
      specific rate of pneumonia-related hospital treatment periods per 1000 persons
      among men was 2.67 (SD 0.17) and among women 1.10 (SD 0.08). The men had more
      treatment periods than the women in every 5-year age group, the greatest
      difference being in the youngest age groups and in the oldest ones. In men the
      mean annual rate of treatment periods increased rapidly after the age of 40 years
      (from 1.54 per 1000 persons in age group 40-45 years to 7.86 per 1000 in age
      group 60-64 years). In women the increase in corresponding age groups was more
      moderate (from 0.77 to 3.19). The increasing number of pneumonia-related hospital
      treatment periods after the age of 40 is facing the challenge for the
      occupational health care in the future.

PMID- 9151003
TI  - An attempt to demonstrate the increased resistance of selected bacterial strains
      during repeated exposure to UV radiation at 254 nm.
AB  - Evidence was provided that in a repeatedly irradiated bacterial suspension of
      Escherichia coli K12: AB 1157, 1886, 2463, under the described experimental
      conditions, gradually mutants more resistant to UV radiation survive. Under these
      circumstances it may happen that selection and an increase of bacterial clones
      with an increased UV resistance develop, manifested by a reduced effectiveness of
      UV radiation during repeated irradiation. Although the cumulating damage of DNA
      in microbes can lead to a reduction of their survival as well as a reduction of
      their absolute numbers, it can be hardly assumed that during practical use in air
      conditioning units or during disinfection of drinking water all bacteria will be
      destroyed. In that case even repeated UV irradiation is not necessarily a
      reliable disinfection tool.

PMID- 9151004
TI  - The effects of storage time on the growth of bacterial flora in bottled drinking
      water.
AB  - An elevated count of mesophilic and psychrophilic bacteria (10(3)-10(4) CFU/1 ml)
      was detected in uncarbonated bottled water stored for a period of 1 year. None of
      the 120 samples contained faecal coliform bacteria or streptococci. Psychrophilic
      and mesophilic bacteria counts detected in bottled water within 24 hours of
      bottling conformed to Czech Republic standard CSN 56 78 59. Counts of the same
      bacteria detected up to 6 months after bottling were also within the limits set
      by the above norm.

PMID- 9151005
TI  - Changes in some psychophysiological parameters in speech information processing
      under masking noise effect.
AB  - The aim of the present work was to study the influence of masking broad-band
      (white), impulse and interrupted noise with intensities LAeq 60 and 90 dB(A) on
      the execution of some psychophysiological tasks. The following parameters were
      studied: pulse frequency and variation, breathing frequency and variation,
      vascular tone etc. The psychological tasks model different parts of the
      operators' activity and include: conduction of mathematical calculations at datum
      speed; test related to the information processing; complex optional task supplied
      by Piorkovski's device. After statistical processing of results by Student
      Fischer's t test and monofactor dispersion analysis it was established that the
      masking noise effect was more strongly expressed in the execution of
      psychophysiological tasks connected with the main memory. Of all tested
      physiological parameters the changes in the peripheral circulation, expressed in
      elevated vascular tone of peripheral blood vessels, were the most significant.

PMID- 9151007
TI  - Urinary epidermal growth factor.

PMID- 9151006
TI  - Health aspects of formaldehyde in the indoor environment. Czech and Slovak
      experience.
AB  - The effects of formaldehyde on human beings has been a subject of study in the
      former Czechoslovakia since the beginning of the 1980s. The first studies quite
      naturally arose from concern over its effects in occupational settings.
      Initially, the allergic effects of formaldehyde on the skin were studied. Two
      main approaches to the study of the biologic effects of formaldehyde on humans
      were employed. The cytogenetic analyses of peripheral lymphocytes and
      immunological analysis of selected humoral immunity parameters were used to
      demonstrate the formaldehyde exposure in both occupational and non-occupational
      indoor environment. The analysis of the results, especially from the non
      occupational settings (e.g. school classrooms), was beset with problems with
      interpretation and lead to suggested maximum acceptable concentration (MAC)
      values that were unrealistically low, ranging from 0.035 mg.m-3 (whole day mean)
      and short term-up to 30 minute sampling 0.050 mg.m-3. These rather stringent
      requirements are fully acceptable for the open air. However, they are difficult
      to achieve in indoor air settings, and are open to criticism from the point of
      view of exposure assessment. Because of the problems in interpreting genotoxic
      and immunological parameters, a risk assessment approach was adopted for this
      discussion.

PMID- 9151008
TI  - Mechanisms influencing the selection of T cell epitopes by MHC class II
      molecules.

PMID- 9151009
TI  - Neurobiological findings in first admission patients with schizophrenia or
      schizophreniform disorder.
AB  - Fifty patients with a DSM-III-R diagnose of schizophrenia or schizophreniform
      disorder were compared to 25 healthy volunteers on structural and functional
      brain measurements. The patients were studied during their first admission to
      psychiatric hospital. In the patient group correlations between structural and
      functional brain measurements and clinical symptoms were performed. Brain
      structure was studied by CT scans. The schizophrenic patients had significantly
      smaller brain volume and brain length and more sulcal, but not ventricular, CSF
      than the controls. These findings were not an effect of sex, abuse, educational
      status or neuroleptic treatment. Brain function was studied by rCBF measurement
      (at baseline conditions and during mental activation), neuropsychological tests
      and neurological examination. The patients had significantly lower rCBF in the
      prefrontal regions during baseline condition and this was more pronounced during
      mental activation when compared with the controls. In the striatal region the
      patients had higher rCBF than the controls during activation. In no other region
      did rCBF differ between the patients and the controls. This points to a
      dysfunction in schizophrenic patients somewhere in th fronto-striatal-thalamic
      circuit. The patients performed poorer than the controls on practically all the
      psychological tests. Especially poor performance was seen in the more complicated
      tests depending on ability of abstraction, planning and sequential organisation
      and on semantic memory. The patients had more neurological abnormalities than the
      controls. Correlations between brain structure and rCBF were few. The
      neurological impaired patient group had more signs of structural brain deficits
      than the neurological normal patient group. Poor performance on a variety of
      psychological tests was correlated to signs of structural cerebral deficits. The
      significant correlations between the neurobiological measurements and clinical
      symptoms in the patients were sparse. However there was a trend that more
      symptoms both positive, negative and thought disorder were correlated to higher
      rCBF values in frontal, temporal and striatal regions, and that absence of
      positive symptoms correlated to structural brain deficits. Thus both structural
      and functional brain deficits can be detected early in the disease of
      schizophrenia. The findings point to primary cortical deficits probably located
      in the frontal and temporo-limbic areas.

PMID- 9151010
TI  - Hip fractures. Epidemiology, risk factors, falls, energy absorption, hip
      protectors, and prevention.
AB  - The present review summarizes the pathogenic mechanisms leading to hip fracture
      based on epidemiological, experimental, and controlled studies. The estimated
      lifetime risk of hip fracture is about 14% in postmenopausal women and 6% in men.
      The incidence of hip fractures increases exponentially with aging, but the time
      trend in increasing age-specific incidence may not be a universal phenomenon.
      Postmenopausal women suffering earlier non-hip fractures have an increased risk
      of later hip fracture. The relative risk being highest within the first years
      following the fracture. Nursing home residents have a high risk of hip fracture
      (annual rate of 5-6%), and the incidence of falls is about 1,500 falls/1,000
      persons/year. Most hip fractures are a result of a direct trauma against the hip.
      The incidence of falls on the hip among nursing home residents is about 290
      falls/1,000 persons/year and about 24% of these impacts lead to hip fracture. The
      force acting on the hip may reach 3.7 kN in falls on the hip from standing
      height, which means that only susceptible subjects will sustain a hip fracture in
      such falls. The effective load acting on the hip is 35% of the body weight in
      unprotected falls on the hip. Women with hip fractures have a lower body weight
      compared with controls, and they may also have less soft tissue covering the hip
      even when adjusted for body mass index, indicating a more android body habitus.
      Experimental studies show that the passive energy absorption in soft tissue
      covering the hip may influence the risk of hip fracture, and being an important
      determinant for the development of hip fracture, maybe more important than bone
      strength. External hip protectors were developed and tested in an open randomised
      nursing home study. The rate of hip fractures was reduced by 50%, corresponding
      to 9 out of 247 residents saved from sustaining a hip fracture. The review points
      to the essentials of the development of hip fracture, which constitutes; risk of
      fall, type of fall, type of impact, energy absorption, and lastly bone strength,
      which is the ultimate and last permissive factor in the cascade leading to hip
      fracture. Risk estimation and prevention of hip fractures may prove realistic
      when these issues are taken into consideration.

PMID- 9151011
TI  - Long-term effects of internally deposited alpha-particle emitting radionuclides.
      Epidemiological, pathological and molecular-biological studies of Danish
      Thorotrast-administered patients and their offspring.

PMID- 9151012
TI  - Regulation of renal sodium and water excretion in the nephrotic syndrome and
      cirrhosis of the liver.
AB  - Atrial natriuretic peptide (ANP) produced in the heart and prostaglandin E2
      (PGE2) synthesised in the kidneys facilitate renal excretion of sodium and water,
      and thus oppose the actions of angiotensin II, aldosterone, arginine vasopressin
      (AVP), endothelin, and the renal sympathetic nerves. In the present work we
      studied the contributions and interactions of these substances in the regulation
      of blood volume (BV), renal haemodynamics, renal sodium and water handling and
      blood pressure (BP) in patients with glomerulonephritis and cirrhosis. The aim
      was through a better understanding of the pathophysiology to improve the
      treatment of fluid retention in these patients, which occurs as development of
      the nephrotic syndrome and accumulation of ascites, respectively. Normotensive
      patients with glomerulonephritis but without the nephrotic syndrome had normal
      baseline BV values measured as the sum of plasma volume and red cell volume; they
      responded to BV expansion after infusion of albumin and BV depletion after
      administration of furosemide with appropriate counterregulatory hormonal changes.
      However, they tended to hold more fluid within the intravascular phase after both
      manipulations than did the healthy subjects. The acutely induced increase in BV
      did not affect the BP, which was likely attributable to the changes in plasma
      values of angiotensin II and ANP shown. ANP could be expected to be a tool in the
      management of fluid accumulation in patients with the nephrotic syndrome and
      cirrhosis. The non-renal effects of high-dose ANP were studied for the first time
      in dialysis patients without excretory kidney function. A reversible shift of
      fluid away from the intravascular phase was demonstrated. The BV was maximally
      reduced 30 min after ANP had been given. The BP was reduced before fluid
      displacement occurred and to the same extent in patients and healthy subjects.
      The reduction in the BV was negatively correlated to the reduction in BP. From
      that study it is inferred that the BP reducing effect of ANP is not mediated by
      its diuretic effect or ability to displace fluid from the intravascular to the
      interstitial fluid compartment. As a pharmacological dose of ANP was given, it
      can only be suggested that endogenous ANP, by altering transcapillary Starling
      mechanisms, assists in buffering intravascular fluid expansion until renal
      excretion or dialysis can take place. The same dose of ANP was given to patients
      with the nephrotic syndrome and cirrhosis. The ability of ANP to increase sodium
      excretion through inhibition of sodium reabsorption in the distal tubules and to
      increase the glomerular filtration rate (GFR) was blunted in both patient groups,
      but the BP was reduced to the same extent as in the healthy controls. Patients
      with the nephrotic syndrome tended to have a slightly elevated BP. We only
      studied patients with normal or slightly reduced GFR. They had a normal BV,
      reduced renal filtration fraction, suppressed aldosterone, increased ANP, but
      normal plasma values of angiotensin II, endothelin, and AVP, and normal urinary
      excretion of PGE2. Thus, neither haemodynamic nor hormonal factors can easily
      explain the spontaneous sodium retention or the resistance to the effects of ANP
      and furosemide. An interesting finding, not previously reported in nephrotic
      humans, was the low cyclic guanosine 3'5'-monophosphate (cGMP) in plasma and
      urine in relation to ANP, both before and after administration of ANP. It is
      hypothesised that renal resistance to ANP, exaggerated renal cGMP degradation, or
      preponderance of clearance receptors in nephrotic kidneys may contribute to
      sodium retention and the low filtration fraction. Elevation of ANP in these
      patients is connected with increased albuminuria, and probably an increase in
      intraglomerular capillary pressure. The resistance to furosemide could not be
      attributed to delayed passage of fluid from the interstitial to the intravascular
      fluid phase, but is most likely due to renal tubular resistan

PMID- 9151013
TI  - Altered calcium homeostasis in the rat cochlear duct and endogenous
      corticosteroid insufficiency.
AB  - Free calcium concentration (CCa2+) profiles were evaluated in perilymph,
      endolymph, marginal cells, spiral ligament and blood serum of adrenalectomized
      (ADX) rats. Free CCa2+ was significantly greater in perilymph and significantly
      reduced in the serum of the ADX animals as compared to sham-operated animals. In
      addition, higher levels of free CCa2+ were found in the spiral ligament in ADX
      animals. Free CCa2+ did not appear to be affected by ADX in marginal cells and
      endolymph. These data suggest that marked reductions in endogenous levels of
      corticosteroids may have a systematic effect on free CCa2+ that is detectable in
      blood serum as well as cochlear fluids and tissues.

PMID- 9151014
TI  - CO2 laser in the diagnosis and treatment of early cancer of the vocal fold.
AB  - A total of 74 patients underwent cordectomy using CO2 laser for either diagnosis
      or treatment of an early cancer of the vocal fold. Type I cordectomy consisted in
      the resection of the entire epithelium, while leaving the vocal ligament intact.
      Type II cordectomy involved removal of the vocal fold from the vocal process to
      the anterior commissure and passing through the inferior thyroarytenoid muscle.
      Type IIIA required vocal fold resection along the internal side of the thyroid
      ala, while type IIIB included removal of the anterior commissure. Type I
      cordectomies were carried out with an Acuspot micromanipulator, which provided a
      250-micron-diameter beam for a working distance of 400 mm, and in the shot-by
      shot cutting mode with 3 W power superpulse. This cordectomy was carried out in
      39 patients and a dysplasia or an early carcinoma were detected in 45.9% of
      cases. Type II and type III procedures were performed with the Microslad
      micromanipulator having a 700-micron-diameter beam in the continuous cutting
      mode, 7 W power superpulse. Fifteen cases were treated by type II cordectomy, of
      which 3 T1aN0M0 cases underwent postoperative radiotherapy due to insufficient
      resections and 2 cases with T1bN0M0 tumors later underwent reconstructive
      laryngectomy. A type III cordectomy was used for 14 cases of T1aN0M0 carcinomas
      and 3 cases of severe dysplasia. The margins of resection were found to be
      positive histologically in 23.5% of these cases, making frozen section
      examinations mandatory at time of surgery. Results of all procedures showed that
      voice was best after a type I cordectomy where only the epithelium was resected.
      In the type II and type III cordectomies, the quality of voice depended on the
      development of a fibrous fold and the absence of anterior synechia in the healed
      larynx.

PMID- 9151015
TI  - The effects of alcohol and smoking upon the age, anatomic sites and stage in the
      development of cancer of the oral cavity and oropharynx in females in the south
      west Netherlands.
AB  - A retrospective review of 303 women, aged 40 or over, with squamous cell
      carcinomas of the oral cavity or oropharynx was conducted in the south-west
      Netherlands to study the effects of smoking and alcohol upon the age of onset,
      site and stage of disease. It was noted that patients presenting with
      oropharyngeal cancers were younger and had a higher incidence of smoking and
      history of heavy drinking. Age at presentation was also affected by the amount of
      alcohol and tobacco consumed with non-users presenting with tumors approximately
      15 years later. A specific finding was that heavy drinkers and smokers tended to
      present with late-stage-disease.

PMID- 9151016
TI  - Prognostic significance of DNA ploidy in mucoepidermoid carcinoma.
AB  - Thirty-four mucoepidermoid carcinomas were studied retrospectively with regard to
      histological and clinical parameters. In 28 of the tumors DNA patterns were also
      assessed using flow cytometry. Twenty-two of the 28 tumors (79%) were DNA diploid
      and 6 (21%) DNA aneuploid. Two tumors (7%) showed intratumoral DNA as indicated
      by different stemlines in specimens investigated from different parts of the
      tumor. DNA ploidy correlated significantly with cervical lymph node status (P <
      0.01), but not with tumor size or histological grade. The mean S-phase value was
      2.7% and was significantly higher in aneuploid samples than in diploid ones (P <
      0.05). The recurrence rate was significantly lower for patients with stage I and
      II tumor compared with those with stage III and IV disease (P < 0.01). Five
      aneuploid tumors showed significantly higher recurrence rates (5/6) than the
      diploid ones (1/22) (P < 0.01). In univariate analysis for survival, only N stage
      tumor (P < 0.05) and tumor DNA ploidy (P < 0.0003) had significant prognostic
      influence. Thus, DNA ploidy seems to be a valuable parameter for evaluating the
      biological behavior of mucoepidermoid carcinomas of the salivary glands.

PMID- 9151017
TI  - Static and dynamic posturography in prevalent laterally directed whiplash
      injuries.
AB  - Static and dynamic posturography was used to study patients who had experienced a
      prevalent laterally directed whiplash in a car accident. Results of both static
      and dynamic examinations were recorded. Findings showed that the whiplash injury
      had provoked shifting of the pressor center of the body toward a side that was at
      least indicative of the kind of cervical twist experienced, even when not
      corresponding to the prevalent direction of the trauma incurred.

PMID- 9151018
TI  - Borders and topographic relationships of the paraglottic space.
AB  - The precise topographic relationships of the paraglottic space (PGS) were
      investigated in serial plastinated or frozen whole-organ sections of 46 normal
      adult larynges. Laterally, the PGS was bordered by the thyroid cartilage.
      Superomedially, the PGS in some specimens was only separated from the
      periepiglottic space by a coherent collagenous fiber septum. The paraglottic
      adipose tissue extended between the caudal fibers of the thyroarytenoid muscle.
      Inferomedially, the PGS was bordered by the conus elasticus. The anteroinferior
      portion of the PGS extended beyond the larynx beneath the inferior rim of the
      thyroid cartilage. Posteroinferiorly, the paraglottic adipose tissue extended
      towards the cricoarytenoid joint. Dorsally, the PGS was bordered by the mucosal
      lining of the piriform sinus. Due to the intimate topographic and histologic
      relationships present, cancer involving the PGS may rapidly infiltrate all
      adjacent anatomic structures.

PMID- 9151019
TI  - Immunohistochemical and electron microscopical characterization of stromal cells
      in nasopharyngeal angiofibromas.
AB  - Twenty-eight cases of nasopharyngeal angiofibroma were studied
      immunohistochemically for cytoskeletal phenotyping of stromal cells. Electron
      microscopy was also used to study the ultrastructure of five of the tumors. All
      typical stromal cells showed intensive immunostaining for vimentin, but were
      negative for smooth muscle actin and desmin. Ultrastructurally, most of these
      cells appeared to be exclusively fibroblasts. However, in some areas stromal
      cells were seen that morphologically resembled myofibroblasts by their shapes and
      arrangement, and were characterized by the coexpression of vimentin and smooth
      muscle actin. Electron microscopy confirmed their myofibroblastic nature. The
      present study showed that the typical stromal cells in nasopharyngeal
      angiofibromas were fibroblasts and not myofibroblasts. In these tumors
      myofibroblasts occurred only focally, in connection with fibrotic areas and
      exclusively as a vimentin+/actin+cytoskeletal phenotype. This indicates that
      myofibroblasts are not primary stromal tumor cells in nasopharyngeal
      angiofibromas, but occur due to regressive changes.

PMID- 9151020
TI  - Staging and treatment of nasopharyngeal angiofibroma.
AB  - To analyze the prognostic value of clinical-radiologic staging, morbidity,
      mortality and results of treatment used in the Instituto Nacional de
      Cancerologia, Mexico, a retrospective study of angiofibroma was performed. Charts
      were reviewed from patients who attended the institute from 1977 to 1993. History
      and physical examination, rhinoscopy and fiber-optic nasopharyngolaryngoscopy
      were done in every patient. Radiologic evaluation was done with computed
      tomography, after which Chandler's staging system was used. Disease-free interval
      curves were estimated for patients who had presented with stage III or IV tumors.
      Thirty-one patients were treated with surgery and/or radiotherapy. Most of the
      patients had stage III (70.9%) or stage JV (25.8%) disease. Surgical procedures
      included lateral rhinotomies (15 cases), transpalatal dissections (11 cases),
      transantral degloving (3 cases), median rhinotomies (2 cases), infratemporal
      transzygomatic dissections (2 cases), frontotemporal craniotomy (1 case) and
      suprahyoid pharyngotomy (1 case). Radiotherapy (as 3000-5500 cGy) was
      administered to 16 patients: 7 patients with stage III persistent or recurrent
      tumor and 8 patients as initial treatment for stage IV disease. The disease-free
      interval of patients with stage III and IV disease was 80.3% and 19%,
      respectively, after 36 months of follow-up. Findings demonstrated that surgery
      was the treatment chosen in patients with stage II and III disease, with low
      morbidity and mortality, and good results in disease control. In contrast,
      radiotherapy was usually the treatment in stage IV disease, but had low
      effectiveness, indicating the need to carefully investigate the value of
      craniofacial approaches in these tumors.

PMID- 9151021
TI  - Mucociliary function of the maxillary sinuses after restoring ventilation: a
      radioisotopic study of the maxillary sinus.
AB  - Ostium patency and sinus ventilation play a key role in the normal function of
      the sinuses and the pathogenesis of sinusitis. Experience with endoscopic
      treatment modalities has indicated that even severe mucosal disease in the
      maxillary and frontal sinuses will heal after eradication of an infectious focus
      in the ethmoid and maintaining ventilation and drainage of sinuses. The aim of
      this study was to use scintigraphic methods to evaluate possible differences in
      mucociliary function of chronically diseased maxillary sinuses after
      establishment of ventilation. Fourteen patients (22 maxillary sinuses) and 3
      controls (6 maxillary sinuses) were evaluated after functional endoscopic sinus
      surgery. The drainage ratios of sinuses at 20 min were calculated at the 3rd
      postoperative day and again at 3 weeks. When the early and late postoperative
      drainage ratios were compared it was found that mucociliary function returned to
      normal after 3 weeks in sinuses with cysts but without hyperplastic mucosal
      degeneration. While the mucociliary function and drainage improved significantly
      in sinuses with hyperplastic mucosa, depending on the severity and extension of
      the pathology present, it was still less than levels found in normal sinuses at 3
      weeks.

PMID- 9151022
TI  - Significance of tubal resection in surgical treatment of middle ear carcinoma.
AB  - We successfully carried out total en bloc resection of squamous cell carcinoma of
      the middle ear in two patients. Both patients have been free of the disease for
      32-39 months. In one of the cases, the eustachian tube was resected totally with
      the temporal bone. Postoperative histopathological examination proved tumor
      invasion into the cartilaginous part of the tube. We would like to emphasize the
      significance of total resection of the eustachian tube when neoplastic invasion
      into the tube is highly suspected. Axial computed tomography is of great value
      for preoperative evaluation of such invasion. Anterior mobilization of the
      carotid artery from the carotid canal facilitates resection of the petrous apex
      and should be done after management of the eustachian tube. The carotid canal is
      best exposed ventrally, since lateral exposure is at high risk for injuring the
      bony part of the eustachian tube and may possibly disseminate tumor cells.

PMID- 9151023
TI  - Implications of United States healthcare reform for European cardiothoracic
      surgery.

PMID- 9151024
TI  - Early experience with single lung transplantation for emphysema with simultaneous
      volume reduction of the contralateral lung.
AB  - OBJECTIVE: Single lung transplantation (SLT) for emphysema has given satisfactory
      long term results in most patients. The mediastinal shift caused by the native
      emphysematous lung may require further surgical intervention in selected cases.
      METHODS: We report a technique of simultaneous SLT and volume reduction of the
      contralateral lung in 4 patients with end stage respiratory failure secondary to
      emphysema. There were two right and two left SLT, performed in two male and two
      female patients. Their mean age was 52.2 (S.D. 4) years (range between 41 and 57
      years) and the ischaemia time averaged 255.6 (S.D. 16) min (range between 225 and
      255 min). The volume of the contralateral lung was reduced using staples. The
      stapled lines were buttressed by the donors pericardium. RESULTS: Their were no
      operative related complications apart from air leak which settled spontaneously
      within 5 days postoperatively. Teh pre-operative FEVI showed a mean value of 0.57
      (S.D. 0.1) L (17.2% (S.D. 2) of the predicted) which improved to 1.79 (S.D. 0.4)
      L (58.2% (S.D. 8) of the predicted) at last follow up (P < 0.005). Radiological
      examinations at 1 year showed central mediastinum with satisfactory respiratory
      function. CONCLUSION: We conclude that this technique can be performed for
      patients with emphysema without increase in the operative morbidity and with good
      early respiratory function. Further follow up is required to assess the long term
      results of this procedure.

PMID- 9151025
TI  - Right ventricular function in the donor heart.
AB  - OBJECTIVES: Early morbidity and mortality post cardiac transplantation is
      frequently caused by right ventricular failure; this is usually attributed to an
      elevated pulmonary vascular resistance in the recipient. Brain death in the donor
      is recognised as causing left ventricular dysfunction, but its effects on the
      right ventricle have not previously been studied. The aim of this study was to
      investigate right ventricular function following brain death, using a canine
      model. METHODS: The hearts of 33 dogs were instrumented with micromanometers,
      flow probes and dimension transducers to measure minor/major axes, and right and
      left ventricular free wall to septal distances. Left ventricular volume was
      calculated according to the prolate ellipsoid model and right ventricular volume
      was calculated according to the shell subtraction method. Systolic function for
      left and right ventricles was analysed by plotting ventricular stroke work vs.
      end-diastolic volume during a caval occlusion (preload-independent recruitable
      stroke work PRSW). Brain death was instigated by inflation of a subdurally placed
      intracranial balloon; subsequently blood pressure was maintained with intravenous
      fluid whilst no inotropic medications were given. Data were collected at
      baseline, and at 2 and 4 h thereafter. A two-tailed paired Student's t-test was
      applied to compare post-brain death data with baseline measurements. RESULTS: All
      animals had an initial hyperdynamic response post brain death ensued by the
      development of diabetes insipidus. Brain stem death was validated by
      neuropathological examination at the termination of the experiments. Right and
      left ventricular systolic function had deteriorated significantly 2 h post brain
      death by 34.4% (+/- 5.1%, P < 0.001) and 20.4% (+/- 3.4%, P < 0.001),
      respectively, from baseline PRSW [RV = 23.6 erg.10(3) (+/- 1.5), LV = 76.2
      erg.10(3) (+/- 3.5)]. This deterioration remained at 4 h post brain death (29.4%
      (+/- 4.9%, P < 0.001) and 21.2% (+/- 4.3%, P < 0.001), respectively). (The
      results are expressed as mean and S.E.M.). CONCLUSIONS: Brain death causes a
      significant decrease in left and right ventricular function. The injury to the
      right ventricle is more prominent than the left ventricle, and at 2 h post brain
      death it is significantly greater. Failure of the right ventricle post
      transplantation in clinical practice may be related to this brain death induced
      injury. Further studies are required to investigate the mechanisms of this
      injury.

PMID- 9151026
TI  - Clinical evaluation of Duraflo II heparin treated extracorporeal circulation
      circuits (2nd version). The European Working Group on heparin coated
      extracorporeal circulation circuits.
AB  - OBJECTIVES: To evaluate whether the application of heparin treated circuits for
      elective coronary artery surgery improves postoperative recovery, a European
      multicenter randomised clinical trial was carried out. METHODS: In 11 European
      heart centers, 805 low-risk patients underwent cardiopulmonary bypass (CPB) with
      either an untreated circuit (n = 407) or an identical but heparin treated circuit
      (n = 398, Duraflo II). RESULTS: Significant differences were found among
      participating centers with respect to patient characteristics, blood handling
      procedures and postoperative care. The use of heparin treated circuits revealed
      no overall changes in blood loss, blood use, time on ventilator, occurrence of
      adverse events, morbidity, mortality, and intensive care stay. These results did
      not change after adjustment for centers and (other) prognostic factors as
      analysed with logistic regression. In both groups no clinical or technical
      (patient or device related) side effects were reported. Because female gender and
      aortic cross clamp time appeared as prognostic factors in the logistic regression
      analysis, a subgroup analysis with these variables was performed. In a
      subpopulation of females (n = 99), those receiving heparin treated circuits
      needed less blood products, had a lower incidence of rhythm disturbances and were
      extubated earlier than controls. In another subgroup of patients with aortic
      cross clamp time exceeding 60 min (n = 197), the amount of patients requiring
      prolonged intensive care treatment (> 24 h) was significantly lower when they
      received heparin treated circuits versus controls. CONCLUSION: These findings
      suggest that improved recovery can be expected with heparin treated circuits in
      specific higher risk patient populations (e.g. females) and when prolonged aortic
      cross clamp time is anticipated. Further investigations are recommended to
      analyses the clinical benefit of heparin treated circuits in studies with
      patients in different well defined risk categories and under better standardised
      circumstances.

PMID- 9151028
TI  - Hemostatic effects of three colloid plasma substitutes for priming solution in
      cardiopulmonary bypass.
AB  - OBJECTIVE: To evaluate the effects on hemostasis of three different plasma
      substitutes with special reference to a newly developed hydroxyethyl starch used
      as priming solution in an extracorporeal circuit as well as peri- and
      postoperative infusion fluid, we studied 36 patients randomly assigned to one of
      three groups, undergoing coronary artery bypass grafting. METHODS: The
      compositions of the priming solutions were: 2.5% hydroxyethyl starch; 3% gelatin;
      and 4% human albumin. Platelet function tests and clotting assays were performed
      on blood samples collected during and after cardiopulmonary bypass. RESULTS: We
      found that plasma von Willebrand Factor remained higher in the human albumin
      group. Hydroxyethyl starch preserved platelet agglutination as well as human
      albumin, whereas platelet aggregation induced by adenosine 5'-di phosphate (ADP)
      proved to be similarly affected during cardiopulmonary bypass in the three study
      groups. Prolongation of the in vitro bleeding constant during the bypass period
      and subsequent partial recovery showed an affected platelet function in all
      groups during cardiopulmonary bypass. The clotting times, activated partial
      thromboplastin time and prothrombin time were similar in the three groups. Blood
      loss, peri- and postoperatively, showed also no differences. Hydroxyethyl starch
      appeared most cost-effective as priming solution in an extracorporeal circuit.
      CONCLUSIONS: We conclude that, with human albumin the golden standard, 2.5%
      hydroxyethyl starch is a suitable colloid plasma substitute to be used as priming
      solution in an extracorporeal circuit as well as peri- and postoperative infusion
      fluid, reasonably well maintaining hemostasis.

PMID- 9151029
TI  - The relation between arterial oxygen tension and cerebral blood flow during
      cardiopulmonary bypass.
AB  - OBJECTIVES: Neurological impairment occurs in up to 25% of infants undergoing
      cardiopulmonary bypass with or without circulatory arrest. Potential causes
      include alterations in cerebral blood flow, hypoxia and embolisation. During
      cardiopulmonary bypass, arterial oxygen tension is maintained at levels which
      under normal conditions cause cerebral vasoconstriction; this is a potential
      mechanism for ischaemia. The aim of this study was to explore the relation
      between arterial oxygen tension and cerebral blood flow during cardiopulmonary
      bypass. METHODS: Near infrared spectroscopy was used to explore the relation
      between arterial oxygen tension and cerebral blood flow in 14 patients (median
      age 8 months; range 1 month to 10 years 11 months). The relations between
      arterial oxygen tension, arterial carbon dioxide tension, temperature,
      haematocrit, pump flow rate, mean arterial pressure and cerebral blood flow, were
      examined using multivariate analysis. RESULTS: There was no relation between
      cerebral blood flow and arterial oxygen tension, but a highly significant
      relation was observed between cerebral blood flow and pump flow rate, with
      cerebral blood flow decreasing 4.2-fold per L.m-2.min-1 decrease of pump flow
      rate. CONCLUSION: There was no relation between arterial oxygen tension and
      cerebral blood flow during cardiopulmonary bypass, but low pump flow rate may
      lead to reduced cerebral blood flow.

PMID- 9151030
TI  - A predictive parameter in patients with brain related complications after cardiac
      surgery?
AB  - OBJECTIVE: The prognostic estimation of cerebral complications after cardiac
      surgery is a major problem in the early postoperative period. Neuron specific
      enolase (NSE) is an enzyme involved in glycolysis, which is localized in neurons
      and axonal processes. It escapes into the blood and cerebrospinal fluid at the
      time of neural injury. Therefore we focused the study on the question of how far
      serum levels of neuron specific enolase can predict the neurological and
      neuropsychological outcome after cardiac surgery. METHODS: We determined, with a
      prospective study design of NSE serum levels in 200 patients undergoing cardiac
      surgery preoperatively, right after the operation and 48 h later. The NSE was
      measured with a solid phase enzyme immuno assay which utilized a highly specific
      monoclonal antibody to NSE. We evaluated the neurological and neuropsychological
      status before and 72 h after surgical intervention. As a control group we
      recruited 50 patients undergoing general surgical treatment. RESULTS: The
      preoperative serum levels of NSE are constantly low in all patients with a mean
      value of 11.1 ng/ml (8.3-13.6) and a mean +/- S.D. of 3.12 in the main group and
      a mean value of 9.6 ng/ml (7.8-10.3) and a mean +/- S.D. of 1.84 in the control
      group. The early postoperative measurements indicated a significant increase to a
      mean value of 19.7 ng/ml (8.7-70.9) with a mean +/- S.D. of 2.89 in the main
      group. In contrast there is no increase of NSE serum levels after general
      surgery. The 48 h postoperative mean levels declined to 14.2 ng/ml (9.9-26.2),
      S.D. of 3.23. In 17 out of the 200 patients a neurological complication occurred.
      Elevated NSE levels were found in 16 of these 17 patients. The highest
      concentrations of NSE were measured in 7 patients with the most severe
      neurological complications being transient ischemic attack and stroke.
      CONCLUSIONS: The early serum levels of NSE after cardiopulmonary bypass, in those
      patients with severe neurological deficits, indicate that NSE is a suitable
      marker for the detection and quantification of cerebral injury after open heart
      surgery. Therefore, in addition NSE seems to be of predictive value for the
      clinical outcome and gives implications for the treatment and prognosis of
      patients with brain related complications in cardiac surgery.

PMID- 9151031
TI  - Serum S-100 protein concentration after cardiac surgery: a randomized trial of
      arterial line filtration.
AB  - INTRODUCTION: Embolization of gaseous and particulate matter is incriminated in
      the neuropsychological morbidity of CPB and can be reduced by membrane
      oxygenators and arterial line filtration. It is not known if the use of arterial
      line filtration in conjunction with membrane oxygenators might have an additive
      effect in reducing cerebral injury. METHODS: Forty patients undergoing elective
      coronary artery surgery were prospectively randomized to a 43 microns heparin
      coated arterial line filter (Cobe Sentry) or to no filtration (control group).
      All operations were performed by one surgeon (DPT) using intermittent ischaemia
      with nonpulsatile CPB, a COBE CML membrane oxygenator and alpha-stat paCO2
      management. Flow rates were maintained between 2.0 and 2.4 l-1 m2 per min with a
      perfusion pressure of 50-80 mmHg and a systemic temperature of 34 degrees C.
      Cerebral injury was defined by careful neurological examination and serial
      measurement of the serum concentration of S-100 protein (a highly specific
      astroglial cell derivative, elevated serum levels of which correlate with proven
      cerebral injury). RESULTS: There was no difference [mean (S.D.)] in the control
      and filter groups with respect to age [61(9) vs. 62(9) years], ejection fraction,
      number of grafts [2.8(0.6) vs. 2.6(0.7)] or CPB times [55(19) vs. 57(18) min].
      Preoperatively, no patient had detectable S-100. In the postoperative period 23
      of 40 patients (58%) showed elevated S-100 levels. At 1, 5 and 24 h the
      respective number of patients in the control and filter groups with elevated S
      100 was (14 vs. 9), (4 vs. 0), (4 vs. 0)) (P < 0.05). No patient had overt
      cerebral injury. CONCLUSIONS: This study suggests that (i) subclinical cerebral
      injury is common (58% of patients in this study) even after apparently
      uncomplicated surgery with short CPB times; (ii) serum S-100 protein is a
      valuable marker for investigating potentially cerebral protective innovations
      during CPB; and (iii) arterial line filtration significantly reduces but does not
      eliminate cerebral injury.

PMID- 9151032
TI  - Surgery of the thoracic aorta using deep hypothermic total circulatory arrest.
      Are there neurological consequences other than frank cerebral defects?
AB  - OBJECTIVE: Deep hypothermic total circulatory arrest has reduced primary
      morbidity and mortality in thoracic aortic surgery. Although frank neurological
      deficits have been proven to be a rare complication of this technique, the rate
      of subtle but irreversible neuropsychological disorders remains unknown. METHODS:
      A total of 23 patients (15 male, 8 female) who had undergone surgery for
      dissection or aneurysm of the thoracic aorta using deep hypothermic total
      circulatory arrest (mean 25.5 min, range 10-75 min) were studied retrospectively.
      The mean follow-up was 17 months. The following psychometric tests were
      conducted: a computer-based test battery to assess tonic alertness and sustained
      attention, the trail making test (TMT part A and B), the Munchner Gedachtnistest
      and a verbal learning test. In addition, a cerebral dopamine D2 receptor
      scintigraphy (using the SPECT technique) was performed. For comparison, 10
      healthy subjects were studied. RESULTS: With regard to tonic alertness, 69.6 and
      30.4% were below the 50th and 10th centiles, respectively, according to age- and
      education-corrected standard values. The impairment in sustained attention
      correlated significantly with the duration of the circulatory arrest. On the
      tests assessing short-term memory, the patients scored 30% below their age- and
      education-corrected peers. In terms of long-term memory, 60.9 and 39.1% of the
      patients were below one and two standard deviations, respectively. Concerning
      speed of information processing whilst 78.3% of the patients were below the 50th
      and 21.7% below the 10th centile. Indicative of some persistent and functional
      brain alteration, the dopamine D2 receptor binding was significantly reduced when
      compared with healthy subjects. CONCLUSIONS: These data prove a substantial and
      chronic reduction of higher cognitive function in some of the patients who
      underwent cardiac surgery using deep hypothermic total circulatory arrest; this
      was accompanied by a depression of the cerebral dopamine D2 receptor binding.

PMID- 9151033
TI  - Retrograde cerebral perfusion through antero-axillary thoracotomy in the aortic
      arch surgery.
AB  - OBJECTIVE: We have recently found that left antero-axillary thoracotomy provides
      an ideal view of aortic arch and makes the direct cannulation to superior vena
      cava possible for retrograde cerebral perfusion during circulatory arrest.
      METHOD: Twelve patients with distal aortic arch aneurysm or aortic dissection
      underwent the repair of aortic arch through this approach. Mean duration of
      retrograde cerebral perfusion was 41 min. RESULTS: Two hospital deaths occurred
      due to respiratory failure and stroke. The remaining patients survived without
      any neurological deficits. CONCLUSION: Antero-axillary thoracotomy may be an
      ideal approach which combines the advantages of median sternotomy and postero
      lateral thoracotomy.

PMID- 9151034
TI  - Re-mediastinoscopy in the assessment of resectability of lung cancer.
AB  - OBJECTIVE: Thirty-one patients underwent re-mediastinoscopy in the diagnostic
      assessment of lung cancer. The reason for a repeat mediastinoscopy was either a
      negative result at the first operation in spite of CT indication of enlarged
      nodes or an incomplete first mediastinoscopy. METHODS: All patients underwent a
      conventional mediastinoscopy. RESULTS: In 22 patients with enlarged mediastinal
      lymph nodes at computed tomography, 10 had a positive lymph node histology at re
      mediastinoscopy, while 12 were negative. In 9 patients with no enlarged
      mediastinal nodes at CT scan, but incomplete biopsies at the first
      mediastinoscopy, 1 patient had lymph node metastases. The median duration from
      the first to the second mediastinoscopy was 43 days. No major complications
      occurred. The staging of the patients was greatly affected by the re
      mediastinoscopy. Of 31 patients judged as operable according to the initial
      mediastinoscopy only 60% were found to be operable following the second
      mediastinoscopy. CONCLUSION: This study has demonstrated the value of re
      mediastinoscopy in assessment of resectability of lung cancer.

PMID- 9151035
TI  - Extended operation for non-small cell lung cancer invading great vessels and left
      atrium.
AB  - OBJECTIVE: We analyzed the results of surgical treatment in patients with non
      small cell lung cancer invading the great vessels (GV) and left atrium (LA) by
      direct extension and without distant metastases. METHODS: From 1976 to 1993, 42
      patients (37/male, 5/female) with lung cancer invading the GV and LA were treated
      surgically, 13 had invasion of the superior vena cava and innominate vein, 15 of
      the aorta and subclavian artery, and 14 of the left atrium. In all 42 the
      diagnosis was confirmed by pathological examination. Surgical resection included
      pneumonectomy (16 patients) and lobectomy (26 patients). The histologic type was
      squamous cell carcinoma in 27 patients, adenocarcinoma in 12, and large cell
      carcinoma in 3. Preoperatively, 13 patients were treated with radiation and
      chemotherapy. Postoperatively, further treatment was given to 22 patients. All
      were staged according to the international TNM staging system. Survival was
      calculated by the Kaplan-Meler method. RESULTS: A total of 15 patients underwent
      complete resection. Reliability of clinical N factor was 80%. The overall
      survival was 17% at 3 years (median survival time (MST), 14 months). The
      operative mortality was 2.4%. Patients with lung cancer invading GV (MST, 19
      months) had significantly longer survival than did those with cancer invading LA
      (MST, 10 months, P = 0.036). There were significant prognostic differences
      between N0-1 and N2-3 (MST, 22 months; MST, 9 months, respectively, P = 0.0013).
      Cox regression analysis identified pathological N factor, completeness of
      resection, and pre- and postoperative radiotherapy as important in affecting
      survival. CONCLUSIONS: We conclude that patients with pathological N0-1 non-small
      cell lung cancer invading great vessels can achieve long-term survival with
      adequate surgical treatment.

PMID- 9151036
TI  - Comparison of two preoperative indices to predict perioperative mortality in non
      cardiac thoracic surgery.
AB  - OBJECTIVE: The preoperative classifications: physical status of the American
      Society of Anesthesiologists (ASA-PS) and/or cardiac risk index (CRI) of Goldman
      are widely used to estimate the perioperative risk in patients undergoing
      noncardiac throacic surgery. We tried to determine the validity of both methods
      in predicting the perioperative mortality in 845 consecutive patients scheduled
      for major elective noncardiac thoracic surgery. METHODS: Preoperatively, each
      patient was assigned 2 independent estimations of risk according to the ASA-score
      (ASA grade, I-IV) and CRI score (CRI grade, I-IV), respectively. RESULTS: Twenty
      five patients died within 4 weeks after the operation, the others survived the
      perioperative period. The grading according to ASA as well as to the CRI score
      showed a direct correlation with the outcome: The higher the preoperative score,
      the higher was the mortality rate. When various combinations of ASA and CRI were
      tested, the lowest mortality rate was found in presence of ASA < or = III and CRI
      = I. Multivariate regression analysis showed that the ASA score had an
      independent correlation with perioperative mortality, whereas such a relationship
      was absent for CRI. CONCLUSIONS: The subjective assessment by an experienced
      anesthesiologist as expressed by the ASA-score is a valid method in the
      determination of the perioperative risk. CRI does not contribute additional
      information for the general perioperative risk.

PMID- 9151037
TI  - Are pulmonary homografts subjected to pulmonary hypertension more appropriate for
      aortic valve replacement than normal pulmonary homografts? Results of
      echocardiography in a multicentric study.
AB  - OBJECTIVE: To compare the function in aortic position of cryopreserved pulmonary
      homografts subjected to pulmonary hypertension with that of normal cryopreserved
      pulmonary homografts. METHODS: Pulmonary valves (52) were implanted in aortic
      position in different cardiothoracic centres. The valves were classified as
      follows: Group I-pulmonary hypertension (procured from recipients of heart/heart
      lung transplantation, 31 valves), Group II-normal pulmonary pressure (procured
      from cadavers and multiorgan donors, 21 valves). Regular echocardiographic follow
      up was obtained by the implanting centers. Significant echo changes were defined
      as insufficiency > 2+ and/or stenosis producing a delta P > 30 mm Hg. RESULTS:
      Pulmonary homografts showed the following significant echo changes: in the
      Pulmonary Hypertension Group, 7, 27 and 33% at 12, 24 and 36 months,
      respectively; in the normal PA Group 10, 37.5 and 80% at 12, 24 and 36 months,
      respectively. In both groups the most common echocardiographic alteration was
      homograft insufficiency rather than stenosis. Thus, pulmonary homografts
      subjected to long-term pulmonary hypertension have significantly less echo
      changes than normal pulmonary homografts, especially after 12 months (chi 2: P <
      0.036). CONCLUSIONS: These findings suggest that pulmonary valves subjected to
      pulmonary hypertension might be more appropriate than normal pulmonary homograft
      for aortic valve replacement, constituting a possible alternative in case of lack
      of aortic valve homografts. However, the failure of two out of five valves in the
      longer term must dictate caution while waiting further long-term results.

PMID- 9151038
TI  - Is the arterial switch operation still a challenge in small centers?
AB  - OBJECTIVE: In the last years, major changes as regards timing for operation,
      surgical technique, and perioperative care determined a great improvement in the
      arterial switch operation (ASO) allowing excellent mid-term results in a few
      leading centers. This stimulated the widespread adoption of ASO as procedure of
      choice for transposition of the great arteries (TGA), even in small institutions.
      We reviewed our early experience with ASO in an attempt to evaluate its safety in
      a small center. METHODS: Since April 1992, 39 consecutive patients underwent TGA
      repair by ASO in our department. There were 27 patients with simple TGA, 8 with
      TGA and VSD and 4 with Taussig-Bing heart and aortic coarctation. Median age and
      weight at operation were 7 days and 3.5 kg, respectively. Neonatal repair was
      performed in 34 patients. In accordance with the Planche coronary classification,
      type I was encountered in 21 patients, type II in 4 and type III in 14. Several
      modifications of the original technique were used, mainly regarding coronary
      relocation, pulmonary artery reconstruction and approaches for associated VSD
      closure and aortic arch repair. RESULTS: Early mortality was 2.6% (n = 1), the
      only operative death being related to unsatisfactory coronary relocation. Since
      modified ultrafiltration was adopted, mean ICU stay decreased from 5 +/- 4 days
      (n = 21) to 2 +/- 1 days (n = 17) (P < 0.05). Three patients required reoperation
      for residual ASD and/or VSD closure. There were no late deaths. After a mean
      follow-up of 26 +/- 15 months all survivors are thriving and are currently
      asymptomatic. CONCLUSIONS: Although this series is rather small, most of the
      major coronary anomalies and complex anatomic associations were encountered. This
      experience suggests that neonatal repair of TGA by ASO can be safely accomplished
      even in small centers. Modified ultrafiltration appears to improve the early
      outcome of neonates undergoing ASO.

PMID- 9151039
TI  - Management strategy and long-term outcome for truncus arteriosus.
AB  - OBJECTIVE: Evaluation of a consistent policy of elective repair of truncus
      arteriosus at 2-3 months of age for the patients who are independent of hospital
      ward care, and long-term outcome. METHODS: Retrospective study of 82 patients
      with truncus arteriosus who underwent total repair at the Victorian Paediatric
      Cardiac Surgical Unit between 1979 and December 1995. The timing was based on a
      consistent policy of elective repair at 2-3 months of age for patients who were
      independent of hospital ward care. Earlier repair was performed when the patients
      were in uncontrolled congestive heart failure. RESULTS: Follow-up was complete
      for all patients with a mean of 76 months (1-183). There were 11 hospital deaths
      (13.4% CL 9-18.5), and five late deaths, actuarial survival at 80 months was 81%
      (CL 70-88%) with 39 patients uncensored at that point. For the purpose of this
      presentation, patients have been grouped according to their age at repair; 1,
      neonates n = 17 (hospital mortality = 5); 2, infants 1-6 months of age n = 48
      (hospital mortality = 4); 3, patients beyond 6 months n = 17 (hospital mortality
      = 2). This series includes 10 patients with interrupted aortic arch with no
      mortality, and 10 patients with discontinuous pulmonary artery (hospital
      mortality = 2). Thirty-seven patients have had 54 conduits replaced to date.
      Using multiple regression, body weight < 3 kg was the only significant
      independent risk factor for hospital mortality. CONCLUSIONS: Our management
      policy tended to gather patients with risk factors described elsewhere into
      presentation group 1 and low risk truncus patients into presentation group 2.
      Deferral of surgery to 2-3 months of age is possible and lowers the surgical
      risk.

PMID- 9151041
TI  - Non-destructive assessment of 62 Dutch Bjork-Shiley convexo-concave heart valves.
AB  - OBJECTIVE: Non-destructive assessment of 62 Bjork-Shiley convexo-concave heart
      valves in view of the risk of fracture and possible detection of defects by means
      of X-ray or acoustics. METHODS: Scanning electron microscopy and stereomicroscopy
      of an unselected sample of valves, representing approximately 70% of the valves
      explanted between 1991 and 1996. Mean duration of implantation was 10.7 +/- 1.9
      years. RESULTS: Six of the 62 valves had a fracture with disk escape. Of the
      remaining 56 valves, 11 (19.6%) had a single-leg fracture and seven (12.5%)
      showed a crack. Valves, 24 (42.8%), revealed no significant defect. After 4600
      days of implantation, large valves (i.e. > or = 29 mm) showed a 6.7 time increase
      in the risk of crack or single-leg fracture compared with smaller valves (OR 6.7,
      95% CI 1.8-24.6, P = 0.04). In a small in-vitro experiment with single-leg
      fracture, rapid smearing occurred, resulting in strut leg separation upon some
      movement. CONCLUSIONS: After approximately 400 x 10(6) cycles, 42.5% of the
      retrieved intact valves was without significant defect, while 32% had a serious
      prefracture defect. Time evolution from defect to fracture remains unpredictable.
      Also, detection of prefracture defects, including single-leg fracture, remains
      difficult, because a "well-detectable' fracture with dislocation is just a brief
      condition. However, technical knowledge can enhance the epidemiological and
      manufacturing information used for clinical decision making.

PMID- 9151040
TI  - Spinal cord protection using hypothermic cardiocirculatory arrest in extended
      repair of recoarctation and persistent hypoplastic aortic arch.
AB  - OBJECTIVE: In recurrent coarctation collateral circulation may not be sufficient
      to maintain adequate perfusion of the lower body during the period of surgical
      repair. Different techniques such as interposition of a Gott-shunt, use of left
      heart bypass or hypothermic cardiocirculatory arrest are used to prevent spinal
      cord injury. METHODS: Twenty-eight operations for recurrent coarctation were
      performed in 26 patients following end-to-end anastomosis (58%), patch plasty
      (21%), subclavian flap aortoplasty (14%) and graft interposition (7%). Associated
      cardiac defects were present in 77% of the patients. Eleven patients who had
      adequate (> 50 mmHg) distal perfusion pressure during a test occlusion were
      operated on using simple cross-clamping (group I, mean age 8.5 +/- 3.8 years). In
      group I, end-to-end anastomosis was performed in nine patients and graft
      interposition in two patients. In 17 cases (including two patients from group I)
      with insufficient collateral circulation and with persistent hypoplasia of the
      arch, hypothermic cardiocirculatory arrest was used (group II, mean age 12.8 +/-
      9.6 years). In group II end-to-end anastomosis was performed in three patients
      and graft interposition in 14 patients. Mean bypass-time was 116 +/- 36 min and
      arrest-time 33 +/- 16 min. Hypothermic cardiocirculatory arrest was begun when
      nasopharyngeal temperature was below 20 degrees C, corresponding to a rectal
      temperature of 24 +/- 3 degrees C. RESULTS: Hypothermic cardiocirculatory arrest
      allowed open reconstruction of the arch and/or complete or partial replacement of
      the arch and the coarctation segment. In-hospital mortality was 0 and 5.9% in
      group I and II, respectively. The one patient who died in group II had
      simultaneous correction of an anomalous pulmonary venous connection and death was
      unrelated to the method of coarctation repair. Reversible laryngeal nerve paresis
      was observed in two patients in group II, no other neurologic complications were
      observed in either group. Postoperative gradients over the repair site were less
      than 20 mmHg by Doppler-echocardiography. Two patients of group I had to have a
      second, early reoperation because of stenosis at the anastomotic site.
      Reconstruction of the distal aortic arch was then performed during hypothermic
      cardiocirculatory arrest. CONCLUSIONS: The use of hypothermic cardiocirculatory
      arrest in this special indication is a safe method which allows open
      reconstruction of the coarctation site and the aortic arch and protection of the
      spinal cord. The need for early reoperation because of inadequate repair may be
      reduced.

PMID- 9151042
TI  - Mechanical cardiac valve thrombosis in patients in critical hemodynamic
      compromise.
AB  - BACKGROUND: Valve obstruction is a life threatening complication of mechanical
      valve prosthesis. METHODS: From 1985 to 1993, 29 consecutive patients were
      hospitalized in our intensive care unit for mechanical prosthetic valve
      thrombosis (PVT). There were 12 men and 17 women aged 25-75 years (57 +/- 12).
      Prosthetic valve location was mitral in 14 patients, aortic in 6, aortic and
      mitral in 9. PVT occurred from 15 days to 174 months (67 +/- 52 months) after
      surgery. Delay from first symptoms to hospitalization ranged from 1 to 45 days
      (11 +/- 11). RESULTS: First clinical symptoms were progressive left heart failure
      in 17 patients, stroke in 6, and chest pain in 6. Furthermore, acute myocardial
      infarction was later documented in 3. Left heart failure NYHA III-IV was present
      in 26 patients (90%) on admission and 10 of those were in cardiogenic shock.
      Anticoagulation regimen was inadequate in 13 cases (45%). It has been recently
      stopped in 8 patients and incorrectly conducted in 5. Total hospital mortality
      was 41.3% (12). It was independent of type and position of the valve prosthesis.
      Diagnosis of PVT was only made at autopsy in 3 patients who died of recurrent
      myocardial infarction (2) or cardiogenic shock (1). Five further patients died
      before any surgery could be attempted (cardiac arrest: 2, cardiogenic shock: 3).
      Valve replacement could be done in 21 cases, 7 of whom were in cardiogenic shock
      and 9 had severe pulmonary edema. Four patients died after surgery, the operative
      mortality was 19%. CONCLUSION: PVT remains a serious complication of mechanical
      heart valve prostheses. Overall mortality rate is high, related to difficulty to
      diagnosis, delay to hospitalization and severe clinical condition at admission.
      In our study, operative risk remained acceptable even when the clinical
      presentation was severe.

PMID- 9151043
TI  - Inhibition of atrial fibrillation by pulmonary vein isolation and auricular
      resection--experimental study in a sheep model.
AB  - OBJECTIVE: The MAZE procedure has proven effective for surgically treating atrial
      fibrillation, but its acceptance has been limited due to the complex dissection
      pattern. A new simplified operative technique, that comprises two important
      components of the MAZE procedure, has been evaluated in an established animal
      model of induced sustained atrial fibrillation. METHODS: In eight sheep, median
      sternotomy was performed for cardiopulmonary bypass via femoral and bicaval
      cannuiation. Bipolar atrial and ventricular electrodes (16) were applied for
      computerized EKG-sampling. Atrial fibrillation was induced during continuous
      theophylline infusion (0.5 mg/kg/min) by repetitive (10x) biatrial stimulation.
      Atrial response was monitored and mapped. The operative procedure was
      accomplished in induced ventricular fibrillation: Right and left atrial
      appendices were resected and a circumferential transmural incision around all
      pulmonary veins was performed and closed. After defibrillation, the atria were
      stimulated again using the above protocol and EKGs were sampled. RESULTS:
      Sustained atrial fibrillation was inducible in all animals (80 stimulation
      episodes, median duration 31 s, 6 incessant episodes) prior to dissection. Post
      resection of the atrial appendices and pulmonary vein isolation, atrial
      fibrillation was not inducible in any of the eight animals (80 stimulation
      episodes). A significant interatrial (104 +/- 13 ms) and atrioventricular (208 +/
      19 ms) conduction delay was observed post dissection. CONCLUSION: We conclude
      that the described procedure is effective for the inhibition of sustained atrial
      fibrillation in morphologically unaltered atria. The operative approach involves
      less dissection than the MAZE procedure, which could facilitate its use in
      concomitant mitral procedures. The clinical significance of the observed AV-Delay
      has to be evaluated.

PMID- 9151044
TI  - Clinical results with single lead VDD pacing.
AB  - OBJECTIVE: For patients with atrioventricular block single lead atrial
      synchronous ventricular pacing (VDD) may have advantages compared to conventional
      dual chamber pacing (DDD) since it eliminates the need for an atrial lead. The
      purpose of this study was to investigate the clinical performance of a novel VDD
      pacemaker and the reliability of atrial sensing via the "floating' atrial
      electrode. METHODS: 31 patients (10 females; age 64 +/- 13 years) underwent an
      implantation of a VDD pacemaker system (Intermedics UNITY). The patients were
      analyzed with regard to implantation parameters, complications and postoperative
      atrial sensing performance using the diagnostic data of the pacemaker memory. The
      mean follow-up was 6.3 (1-18) months. RESULTS: The implantation procedure did not
      differ from that of conventional single chamber pacemakers. Dislocation of a
      ventricular electrode was the only complication observed. The P wave at
      implantation was 1.6 +/- 0.9 mV and dropped to 0.9 +/- 0.4 mV at predischarge.
      During follow-up the atrial sensing threshold remained stable. The atrial sensing
      performance (percentage of atrial synchronous ventricular complexes) after
      reprogramming the highest atrial sensitivity was 99.7%. Two patients (6%)
      developed atrial fibrillation. 29 patients (94%) remained in VDD mode as
      primarily intended. CONCLUSIONS: From these results it is concluded that VDD
      pacing represents an excellent alternative in patients with atrioventricular
      block and intact sinus node function. The atrial sensing was found to be
      reliable.

PMID- 9151045
TI  - Systemic candidiasis in cardiac surgery patients.
AB  - OBJECTIVE: To examine the frequency, predisposing factors and consequences of
      systemic candidiasis in cardiac surgery patients. We also examined fluconazole
      efficacy in the treatment of disseminated fungal disease. METHODS: A total of
      2615 adult patients of mean +/- S.D. age 60.8 +/- 8.7 years who underwent open
      heart surgery between July 1993 and April 1995, were enrolled in the initial
      protocol. Patients were divided in two groups according to length of stay in the
      intensive care unit (ICU). The cut-off was a length of stay of 9 days. RESULTS:
      In the group of patients with prolonged stay (n = 54), 11 patients (20.3%)
      developed systemic candidiasis, usually after the twentieth postoperative day.
      Predisposing factors were patient age, history of diabetes mellitus, presence of
      central venous catheters, prolonged mechanical ventilatory support, prolonged ICU
      stay, and administration of antibiotics and of total parenteral nutrition for a
      prolonged period. The patients who developed systemic candidiasis had a median
      ICU and hospital stay of 58 and 60 days respectively. The mortality rate was
      27.2%. Patients receiving fluconazole, improved and eventually negative cultures
      were obtained. CONCLUSIONS: We concluded that a significant percentage of
      patients who remained in the cardiothoracic ICU for more than 9 days developed
      systemic candidiasis. Systemic candidiasis resulted in a significant prolongation
      of ICU and hospital length of stay, thus increasing extensively total
      hospitalization costs. Fluconazole seems to be an effective and well-tolerated
      agent in the treatment of severe life-threatening systemic candidiasis, and a
      very good alternative to amphotericin B, in cardiac surgery patients.

PMID- 9151046
TI  - Coronary revascularisation in young adults.
AB  - OBJECTIVE: To evaluate the long-term outcome of coronary artery bypass surgery
      (CABG) in patients < 40 years old and to determine factors predictive of adverse
      outcomes. METHODS: Retrospective review of data on 220 patients who underwent
      isolated CABG at Green Lane Hospital, New Zealand from 1970 to 1992. RESULTS: The
      actuarial survival after surgery was 91, 74 and 50% at 5, 10 and 15 years,
      respectively. Recurrence of ischaemic symptoms occurred at a median time of 72
      months, and only 20% of patients remained asymptomatic 10 years after CABG.
      Univariate analysis of potentially adverse surgical factors showed that patients
      who had prolonged bypass time (> or = 100 min, P < 0.007) had increased late
      mortality. There were two distinct operative eras with respect to the use of IMA
      conduits (4% pre 1985, 87% post 1984) The relationship between IMA conduits use
      and survival was significant on time independent analysis (P < 0.02), but was not
      using the log-rank test. Preoperative clinical characteristics associated with
      increased late mortality were impaired left ventricular function (end-systolic
      volume (ESV) > or = 80 ml, P = 0.008; ejection fraction < 40%, P = 0.0005), and
      lack of aspirin use either pre- or post-operatively (P < 0.0001). Multivariate
      analysis indicated that reduced ejection fraction (P = 0.04) and prolonged bypass
      time (P = 0.05) was associated with an increased risk of late death. Aspirin
      therapy (P = 0.001) was associated with decreased late mortality. Cumulative
      events rate of reintervention and mortality was reduced in female patients (P =
      0.0009). At review, 45% of patients had total cholesterol > 6.5 mmol/l.
      CONCLUSION: To avoid the early recurrence of symptoms, the need for
      reintervention and late mortality, young patients should receive IMA conduits,
      cardioplegia as myocardial protection, aspirin and therapy to modify/ameliorate
      their risk factors including dyslipidaemia, diabetes and left ventricular
      dysfunction.

PMID- 9151047
TI  - Recombinant hirudin as an anticoagulant during cardiac operations: experiments in
      a pig model.
AB  - OBJECTIVE: The efficacy and safety of recombinant hirudin (r-hirudin) compared
      with heparin as an anticoagulant during open-heart surgery has been studied in a
      pig model. METHODS: A total of 18 Gottingen minipigs were randomly divided into
      three treatment groups and subjected to cardiopulmonary bypass for 1 h. Heparin
      treated animals received a bolus of unfractionated heparin of 400 IU/kg body
      weight. Recombinant hirudin was given by a bolus injection of 1 mg/kg body
      weight, followed by a 1 h lasting infusion of 1 mg/kg body weight per h. The
      heparin-anticoagulated animals and one group of the hirudin-treated animals
      additionally received aprotinin at a dosage of 17500 KIU/kg body weight (KIU,
      kallikrein inhibitory units). In the second group of r-hirudin-treated animals,
      the aprotinin was replaced by saline. RESULTS: The extracorporeal circuit
      remained patent for a 1 h pump period in all of the animals studied. There was no
      evidence of vascular occlusion or clot formation in the r-hirudin-treated
      animals. The anticoagulant efficacy of the hirudin protocol used is further
      demonstrated by the results of electron-microscopical scans of the pump-line
      filters. Fibrin deposits were visible only in the heparin-treated animals and not
      in r-hirudin-treated pigs. Despite this strong anticoagulant effect, there was no
      evidence of an increased bleeding tendency in r-hirudin-treated pigs. Moreover,
      histological studies showed a statistically significant (P < 0.05) higher
      incidence of tissue bleeding in the heparin/aprotinin-treated animals compared
      with the r-hirudin/aprotinin-treated pigs. Studying the platelet function, a
      statistically significant (P < 0.01) better preserved ADP- and collagen-induced
      platelet aggregation was seen in the r-hirudin/aprotinin-treated animals when
      compared with heparin/aprotinin-treated animals. CONCLUSIONS: These data
      demonstrate that r-hirudin can be used successfully as an alternative
      anticoagulant to heparin during cardiac operations including cardiopulmonary
      bypass. The better preservation of platelet function suggests that r-hirudin may
      reduce the postoperative risk of bleeding.

PMID- 9151048
TI  - Postischemic synthesis of high energy phosphates in isolated porcine hearts
      during reperfusion with 11 or 25 degrees C hypothermic perfluorocarbon emulsion
      FC 43. A 31P magnetic resonance spectroscopy study.
AB  - OBJECTIVE: One aim of coronary reperfusion after myocardial ischemia is to
      restore the myocardial content of high energy phosphates. The superiority of the
      artificial oxygen carrier perfluorocarbon emulsion FC43 over blood solution is
      known, therefore, in this paper we examined the temperature-dependence of this
      substance. METHOD: The changes of the high energy phosphates phosphocreatine
      (PCr) and inorganic phosphate (Pi) were documented in 29 isolated pig hearts,
      employing a 4.7 Tesla magnetic-resonance-spectroscope (MRS). After 15 min warm
      ischemia, reperfusion with warm blood and a cardioplegic ischemia period of 45
      min, these hearts were reperfused with either 11 or 25 degrees C hypothermic
      oxygenated perfluorocarbon emulsion FC43, both under continuous spectroscopy. MRS
      is able to directly measure PCr as well as Pi. Their relation expresses the state
      of myocardial energy stores. RESULTS: Reperfusion with 11 degrees C hypothermic
      FC43 (n = 14) caused an increase of the relation PCr to Pi by a factor of 9,
      compared to an increase by a factor of 4 with 25 degrees C emulsion (n = 15) (P <
      0.05). During 80 min of reperfusion with 11 degrees C cold FC43 emulsion the
      average flow rate was 90 +/- 12 and 96 +/- 11 ml/min during reperfusion with 25
      degrees C hypothermic FC43 emulsion. Both rates fell only slightly in the course
      of time. CONCLUSION: We conclude that reperfusion with 11 degrees C hypothermic
      oxygenated FC43 in isolated ischemic porcine hearts leads to a clear increase of
      the index PCr/Pi compared with reperfusion at 25 degrees C. The correlation
      between the synthesis of myocardial high energy phosphates with postcardioplegic
      ventricular function is questionable. If further studies will show an improvement
      of myocardial function after perfusion with hypothermic oxygenated
      perfluorocarbon emulsion FC43, this solution may find clinical application in the
      storage of explanted human hearts for transplantation, during transportation to
      the recipient.

PMID- 9151049
TI  - Effect of cardioplegia infusion pressure on coronary artery endothelium and
      cardiac mechanical function.
AB  - OBJECTIVE: Monitoring of cardioplegia infusion pressure may be important,
      particularly in immature hearts and in hearts without coronary artery disease. We
      have investigated the effects of infusion pressure on the preservation of the
      isolated rat heart. METHODS: Hearts (five in each group) were subjected to a
      single (20 ml) infusion of St. Thomas' Hospital cardioplegic solution at
      pressures of 60, 120, 180 and 240 cmH2O (44-176 mmHg), followed by 30 min of
      hypothermic (20 degrees C) ischemia. RESULTS: Mean recovery of cardiac output
      (expressed as a percentage of its preischemic value) decreased with increasing
      infusion pressure: 96.1 +/- 0.6%, 87.3 +/- 2.1% (P < 0.05 vs. 60 cmH2O), 79.3 +/-
      2.8% (P < 0.05 vs. 120 cmH2O), 72.0 +/- 3.0% (not significant vs. 180 cmH2O),
      respectively. Endothelial function, as assessed by pre- and post-ischemic ability
      to secrete NO in response to 5-hydroxytryptamine, remained relatively normal
      after infusion at 60 cmH2O, but changed from vasodilation to vasoconstriction
      after infusion at 240 cmH2O. Electron microscopy revealed mild endothelial damage
      after infusion at 240 cmH2O, which was greatly exacerbated by reperfusion and was
      accompanied by regions of myocyte damage compatible with reperfusion of
      unprotected myocardium. The relationship between cardioplegia infusion pressure
      and infusion time was not linear and implied that infusion pressures greater than
      120 cmH2O caused vascular smooth muscle constriction. CONCLUSIONS: These results
      suggest that even mildly raised cardioplegia infusion pressures may be
      detrimental to cardiac preservation and the effects are possibly mediated through
      endothelial damage and pressure-induced coronary vasoconstriction.

PMID- 9151050
TI  - Plasma levels of immunoinhibitory cytokines interleukin-10 and transforming
      growth factor-beta in patients undergoing coronary artery bypass grafting.
AB  - OBJECTIVE: Cardiovascular surgery with extracorporeal circulation causes a
      systemic inflammatory response, which can lead to organ failure and increased
      postoperative morbidity. Advances in knowledge about the interactions between
      markers of cellular and humoral immunity involved in the inflammatory response to
      cardiopulmonary bypass (CPB) may reduce the deleterious effects and improve the
      outcome for patients undergoing cardiac surgery. METHODS: To determine the
      release of immunoinhibiting cytokines during CPB, we measured plasma levels of
      interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) in 30
      patients undergoing elective coronary artery bypass grafting. Arterial blood
      samples were collected at eight time points before, during and after CPB, using a
      standardized ELISA-technique. RESULTS: Plasma IL-10 and TGF-beta increased
      significantly after weaning off CPB (P < 0.05) and peaked respectively at time of
      skin closure (IL-10, 308 +/- 180 pg/ml; TGF-beta, 1860 +/- 906 pg/ml; mean peak
      +/-S.D.). Postoperatively, 6 h, IL-10 decreased to 19.8 +/- 9.8 pg/ml (P < 0.05)
      and TGF-beta decreased to 1133 +/- 547 pg/ml (P < 0.05). CONCLUSIONS: Both
      cytokines are major immunoregulatory factors with negative influence on T cell
      mediated immunologic response. The significantly elevated levels at the end of
      CPB indicate that IL-10 and TGF-beta may be important factors of immunologic
      dysregulation following CPB.

PMID- 9151051
TI  - Phosphatidylcholine coated chest drains: are they better than conventional drains
      after open heart surgery?
AB  - INTRODUCTION: Inadequate thoracic drainage after open heart surgery has serious
      deleterious consequences. Thrombus formation within the chest drains is primarily
      responsible for the occlusion of chest drains. Chest drains coated with
      derivatives of phosphatidylcholine (PC), commonest phospholipid on cell
      membranes, potentially have a less thrombogenic surface. MATERIALS AND METHODS:
      In a prospective randomised double blind study, we compared PC-coated drains
      (Group I, n = 25) with non coated drains (Group II, n = 26) after open heart
      surgery. Drain performance, post-operative complications and clinical course were
      compared. RESULTS: PC-coated drains had a significantly shorter period of
      drainage, 20.4 +/- 1.0 versus 28.9 +/- 3.7 h (P < 0.05). Otherwise, mean volume
      drained, number clots removed from drain and the ease of drainage of the two
      types of drains were similar. There were no significant differences in the
      incidence of post-operative pericardial effusions, dysrhythmias, ambulation time
      and hospital stay. CONCLUSIONS: We conclude that the PC coated drains may be of
      importance in cases where prolonged drainage is anticipated otherwise they have
      no significant advantage.

PMID- 9151052
TI  - Bilateral thoracoscopy for sympathectomy in the treatment of hyperhidrosis.
AB  - Thoracoscopic sympathectomy has been established as the least invasive technique
      with high success rates for treatment of palmary hyperhidrosis [1,4,5]. In our
      procedure both sides are treated during the same operation. A bilateral
      thoracoscopy was performed in 20 patients for incapacitating hyperhidrosis.
      Immediate complications at operation were minimal. All patients reported
      satisfaction with the procedure in spite of compensatory sweating. The short
      hospital stay has significant financial benefits and these are increased if both
      sides are treated at the same time. This procedure is more aggressive than the
      single side procedure but the morbidity is not increased.

PMID- 9151053
TI  - Simplified technique for antegrade cerebral perfusion.

PMID- 9151054
TI  - Acute bicaval obstruction as a result of intracapsular haemorrhage in a right
      atrial myxoma: report of a case.
AB  - Right atrial myxomas are rare and presentation is characterised by the gradual
      onset of one or more of a triad of constitutional, obstructive, or embolic
      symptoms. We describe a case in which interstitial haemorrhage within a right
      atrial myxoma resulted in rapid expansion and presentation with features of
      rapidly progressing bicaval obstruction and atrial flutter. Transthoracic
      echocardiography failed to detect this tumour; however, transoesophageal echo
      clearly displayed it and gave information on its attachment and relations which
      proved to be valuable in the planning of its surgical excision.

PMID- 9151055
TI  - Intramural right atrial myocardial hemangioma treated by emergency surgery.
AB  - An unusual case of myocardial cavernous hemangioma causing dissection of the
      right atrial wall is described. A subsequent intramural hematoma presented as an
      extensive pseudotumor of the heart and was complicated by hematopericardium and
      tamponade. Tumor resection could be performed successfully. Diagnostic approach,
      surgical treatment and histopathological findings are presented.

PMID- 9151057
TI  - Bilateral internal mammary artery atherosclerosis: a late complication of delayed
      repair of coarctation of the aorta.
AB  - A 58-year old patient who had undergone repair of aortic coarctation at 19 years
      of age, subsequently developed coronary artery disease requiring coronary artery
      bypass surgery. At operation both internal mammary arteries were found to be
      totally occluded with calcific atherosclerosis. We therefore advise that the
      internal mammary arteries should be assessed carefully in patients with similar
      past histories.

PMID- 9151056
TI  - Lipomatous hypertrophy of the interatrial septum: indication for surgery?
AB  - A fortuitous finding during open heart surgery of lipomatous hypertrophy of the
      interatrial septum is described in a 65-year old man with ischaemic heart
      complaints due to coronary artery disease and with premature ventricular
      contractions. An incision biopsy confirmed the diagnosis. The choice of treatment
      of lipomatous hypertrophy of the interatrial septum is controversial. Indications
      for surgery and surgical techniques are discussed.

PMID- 9151058
TI  - Failure of gastroepiploic artery graft due to gastroduodenal artery stenosis.
AB  - We report a patient with recurrent angina after gastroepiploic artery grafting to
      the right coronary artery because of a stenotic lesion of the gastroduodenal
      artery, which limited blood flow through the right gastroepiploic artery graft
      and caused myocardial ischemia. The patient was successfully treated by saphenous
      vein grafting to the right coronary artery without cardiopulmonary bypass.

PMID- 9151059
TI  - Anomalous coronary artery fistula with simultaneous drainage to the left atrium
      and the coronary sinus.

PMID- 9151060
TI  - Extracorporeal membrane oxygenation and the treatment of critical pulmonary
      hypertension in congenital heart disease.

PMID- 9151061
TI  - The use of low-dose aprotinin, epsilon-aminocaproic acid or tranexamic acid for
      prevention of mediastinal bleeding in patients receiving aspirin before coronary
      artery bypass operations.
AB  - Patients undergoing primary myocardial revascularization were randomized to one
      of three drug regimens (low-dose aprotinin, epsilon-aminocaproic Acid or
      tranexamic Acid) to determine which drug regimen would most effectively reduce
      post-operative bleeding and the need for blood products. All patients had
      received 325 mg of aspirin within 48 h before operation. All three drug regimens
      reduced the requirements for blood products and postoperative bleeding after
      coronary artery bypass operations. There was, however, no significant difference
      between drug regimens.

PMID- 9151062
TI  - Resin composites in dentistry: the monomer systems.
AB  - The present review outlines the history of monomers used in resin composites,
      motivates further development, and highlights recent and ongoing research
      reported in the field of dental monomer systems. The monomer systems of most
      present-day resin composites are based on BisGMA, developed some 40 years ago, or
      derivatives of BisGMA. In the remaining resin composites, urethane monomers or
      oligomers are used as the basis of the monomer system. The main deficiencies of
      current resin composites are polymerization shrinkage and insufficient wear
      resistance under high masticatory forces. Both factors are highly influenced by
      the monomer system, and considerable efforts are being made around the world to
      reduce or eliminate these undesirable properties. The use of fluoride-releasing
      monomer systems, some of which are under investigation, has been suggested to
      mitigate the negative effects of marginal gaps formed in consequence of
      polymerization shrinkage. The very crux of the problem has also been approached
      with the synthesis of potentially low-shrinking/non-shrinking resin composites
      involving ring opening or cyclopolymerizable monomers. By the use of additives
      with a supposed chain transfer agent function, monomer systems have been
      formulated that improve the degree of conversion of methacrylate double bonds and
      mechanical properties. Many promising monomer systems have been devised, the
      implementation of which may be expected to improve the longevity of resin
      composite fillings and expand the indications for resin composites.

PMID- 9151063
TI  - Dental anxiety among adolescents in St. Petersburg, Russia.
AB  - This small-size epidemiologic investigation examined the prevalence and etiology
      of dental fear and anxiety among 288 schoolchildren aged 13-18 years in St.
      Petersburg, Russia. The adolescent population was collected from a larger
      sociological investigation performed in Russia during the early period of
      reforms. The investigation revealed a comparatively elevated anxiety level with
      an average DAS score of 10.0 and a prevalence of high dental fear of 12.6%. The
      present study showed that the origin of dental anxiety as reported by adolescent,
      urban Russians parallels much of previous results from the US and Western Europe.
      Thus, the etiology of dental anxiety was related to negative dental experiences
      and this conditional learning seemed to be especially prevalent in the presence
      of previous oral pain experiences and an existing dental anxiety in the family.

PMID- 9151064
TI  - Hypothetical mortality risk associated with spiral tomography of the maxilla and
      mandible prior to endosseous implant treatment.
AB  - Radiation dose delivered from the SCANORA radiography unit during the cross
      sectional mode for dentotangential projections was determined. With regard to
      oral implantology, patient situations of an edentulous maxilla and mandible as
      well as a single tooth gap in regions 16 and 46 were simulated. Radiation doses
      were measured between 0.2 and 22.5 mGy to organs and tissues in the head and neck
      region when the complete maxilla or mandible was examined. When examining a
      single tooth gap, only 8% to 40% of that radiation dose was generally observed.
      Based on these results, the mortality risk was estimated according to a
      calculation model recommended by the Committee on the Biological Effects of
      Ionizing Radiations. The mortality risk ranged from 31.4 x 10(-6) for 20-year-old
      men to 4.8 x 10(-6) for 65-year-old women when cross-sectional imaging of the
      complete maxilla was performed. The values decreased by 70% when a single tooth
      gap in the molar region of the maxilla was radiographed. The figures for the
      mortality risk for examinations of the complete mandible were similar to those
      for the complete maxilla, but the mortality risk decreased by 80% if only a
      single tooth gap in the molar region of the mandible was examined. Calculations
      according to the International Commission on Radiological Protection carried out
      for comparison did not reveal the decrease of the mortality risk with age and
      resulted in a higher risk value in comparison to the group of 35-year old
      individuals in calculations according to the Committee on the Biological Effects
      of Ionizing Radiations.

PMID- 9151065
TI  - Intraepithelial lymphocytes bearing the gamma/delta receptor in the oral and
      jejunal mucosa in patients with dermatitis herpetiformis.
AB  - Lymphocytes bearing T cell receptor (TcR) gamma/delta are increased in the
      jejunal mucosa of patients with dermatitis herpetiformis (DH) and coeliac
      disease. In this study, we examined whether increased numbers of gamma/delta TcR
      positive lymphocytes occur in the oral mucosa of patients with DH. Oral and
      jejunal mucosal biopsies were taken from 13 newly diagnosed and 13 gluten free
      diet (GFD)-treated patients with DH. Monoclonal antibodies and avidin-biotin
      peroxidase method was used for staining, and TcR positive cells were counted from
      the buccal and jejunal epithelium. Very few gamma/delta TcR positive lymphocytes
      were seen in the buccal epithelium of untreated or GFD-treated DH patients
      (median 0.4 and 0.3 cells/mm2), whereas alpha/beta TcR positive lymphocytes were
      frequent in both groups of DH patients (154 and 250 cells/mm2) and healthy
      controls (135 cells/mm2). The numbers of gamma/delta TcR positive intraepithelial
      lymphocytes were significantly increased in the jejunum of both untreated (43
      cells/mm) and GFD-treated (27 cells/mm) DH patients compared to control patients
      (2.2 cells/mm). The present study did not, therefore, disclose any evidence for
      active recruitment of gamma/delta TcR positive lymphocytes in the oral
      epithelium, but showed substantial amounts of intraepithelial alpha/beta TcR
      positive lymphocytes both in DH patients and healthy controls.

PMID- 9151066
TI  - Changes in TGF-beta 1 levels in gingiva, crevicular fluid and serum associated
      with periodontal inflammation in humans and dogs.
AB  - Transforming growth factor-beta (TGF-beta) represents a family of polypeptide
      growth factors, involved in embryogenesis, inflammation, regulation of immune
      responses and wound healing. To determine whether TGF-beta contributes to the
      evolution of periodontal disease, we assayed TGF-beta levels in gingiva and
      crevicular fluid of patients with gingivitis and periodontitis. In parallel, TGF
      beta was quantified in gingival fluid and serum of beagles with experimentally
      induced periodontitis. Disease was monitored by several clinical parameters
      including Plaque Index, Gingival Index, probing depth, and epithelial attachment
      loss. Gingival tissues were obtained from 9 patients at the time of periodontal
      surgery, and gingival fluid samples were collected from an additional population
      of 10 periodontal patients. In 14 beagles, experimental periodontitis was induced
      and gingival fluids collected 6 months later. Fluid was collected by paper strips
      and volume measured by Periotron. Additionally, sera was collected before and 9
      months after the ligature-induced periodontitis in 7 beagles. The levels of TGF
      beta 1 were measured by ELISA. In the patients, a significantly higher
      concentration of TGF-beta 1 was observed both in the gingival tissues and fluid
      samples obtained from the sites with deeper periodontal pockets than in the less
      involved sites. In beagles, TGF-beta 1 levels measured in gingival fluid were
      elevated in moderate disease, declining in fluid samples obtained from the
      pockets during more advanced experimental periodontitis. Furthermore, with the
      progression of experimental periodontitis, a decrease in TGF-beta 1 occurred in
      the sera of the beagle dogs. These data suggest that TGF-beta 1 may play a role
      in the pathogenesis and diagnosis of periodontal disease, and that its actions
      can be further explored in an animal model.

PMID- 9151067
TI  - Quantification of human myeloperoxidase in oral fluids.
AB  - Peroxidase activity in human whole saliva is derived from salivary peroxidase and
      myeloperoxidase. Present spectrophotometric assays are relatively non-specific
      and influenced by ions present in salivary secretions, resulting in an over
      and/or underestimation of peroxidase activities. Specific polyclonal or
      monoclonal antibodies would greatly simplify the identification of salivary
      peroxidase and myeloperoxidase in human saliva and determine the relative
      contribution of each enzyme to the total peroxidase activity in human saliva. In
      the present study, a highly purified preparation of myeloperoxidase was used to
      raise polyclonal antibodies against the antigen. The antibodies were purified and
      extensively characterized in terms of their ability to interact with the antigen,
      with other mammalian peroxidases, and with other proteins present in salivary
      fluids. The antibodies recognized only myeloperoxidase and did not cross-react
      with any of the substances tested, showing that these antibodies can be used to
      detect and differentiate myeloperoxidase from other peroxidases in saliva. We
      have also developed and tested a sandwich ELISA which can be used in a clinical
      setting to quantify myeloperoxidase in whole saliva and gingival crevicular
      fluid.

PMID- 9151068
TI  - Oral, perioral and systemic pathosis in HgCl2-induced autoimmunity in the BN rat.
AB  - Male BN rats were repeatedly skin-injected with HgCl2 solution and sacrificed
      after 6, 9, 14, 21, 28 or 24 days. Mononuclear cell infiltrates were observed in
      the oral mucosa and in lacrimal, salivary and thyroid glands from 6-9 days
      onwards, with a peak at 14-21 days. Immunohistochemistry identified these cells
      as predominantly T cells with some NK cells but very few B cells. Reversible
      parenchymal changes were observed but there was no obvious persistent tissue
      destruction. Serum titers of IgE, IgG1, anti-laminin and anti-DNP, but not IgG2a
      antibodies, were raised and peaked at 14-21 days. However, there was no
      correlation, within animals, between these titers and the extent of mononuclear
      cell infiltration. Mercury was histochemically detected within dendritic
      cells/macrophages in the connective tissue stroma of the glands and in the oral
      mucosa, but no correlation was found between the distribution of mercury and the
      degree of inflammation. We conclude that the accumulation of mononuclear cells in
      oral and perioral tissues of HgCl2-treated BN rats does not represent a local
      immune response to tissue-retained Hg. Instead, we propose that the extravasation
      represents an epiphenomenon that is not necessarily deleterious to the
      infiltrated organ.

PMID- 9151069
TI  - Effects of frequent mouthrinses with palatinose and xylitol on dental plaque.
AB  - The aim was to evaluate the effects of frequent mouthrinses with palatinose,
      xylitol and a mixture of palatinose and xylitol on plaque pH, plaque formation
      and cariogenic microorganisms. 15 subjects refrained from toothbrushing during 3
      test periods and rinsed 15 x daily for 4 d with 10 ml of: (1) 50% palatinose, (2)
      37.5% palatinose + 12.5% xylitol, or (3) 50% xylitol. A contrast period with no
      mouthrinses was also carried out. The 4 periods were carried out in a randomized
      order with a cross-over design. After the 4-day periods, 3 parameters were
      measured: (1) plaque pH during the first 30 min after a mouthrinse with
      palatinose, a mixture of palatinose and xylitol or xylitol alone, directly
      followed by a 2nd rinse with 10% sucrose; (2) number of mutans streptococci and
      lactobacilli in plaque and saliva; (3) plaque index. The most pronounced pH drop
      for the sugar substitutes was found when rinsing with 50% palatinose after the
      palatinose period, and the least pH drop with 50% xylitol after the xylitol
      period. The sucrose rinse gave similar pH fall after all 4 periods. The microbial
      data showed no differences between the 4 periods, but the mutans streptococcus
      counts in saliva decreased after the xylitol period in contrast to the 3 other
      periods. Regarding the plaque index, xylitol gave lower scores compared to the
      other 3 periods.

PMID- 9151071
TI  - Are sodium lauryl sulfate-containing toothpastes suitable vehicles for xylitol?
AB  - The hypothesis to be tested in this study was that toothpastes containing sodium
      lauryl sulfate (SLS) is unsuitable vehicles for xylitol. The bacteriostatic (and
      cariostatic) effect of xylitol is assumed to be caused by intracellular
      accumulation of xylitol-5-P in plaque bacteria. Experiments were designed to
      investigate whether presence of SLS would affect the uptake of xylitol by
      interacting with the bacterial membranes and thus inhibit xylitol-5-P formation.
      It was shown in an in vitro study that even very low concentrations of the strong
      anionic detergent SLS inhibited uptake of xylitol and xylitol-5-phosphate
      formation by dental plaque totally. The mild nonionic detergent ethoxylated
      stearyl alcohol (30x EO) had no such effect. In vivo experiments with toothpastes
      containing xylitol and either the strong or the mild detergent, showed that
      xylitol in toothpaste with SLS was not available for the plaque bacteria and gave
      no adaptation to xylitol, whereas in the presence of 30x EO it was available, and
      a xylitol adaptation was observed. Glucose metabolism, which was also studied for
      the plaque samples, was not significantly affected by presence of any of the 2
      detergents, indicating that the amounts of xylitol in toothpastes were presumably
      too low to give clinical significant effects, even when mild detergents are used.

PMID- 9151070
TI  - Effects of xylitol, xylitol-sorbitol, and placebo chewing gums on the plaque of
      habitual xylitol consumers.
AB  - Xylitol reduces plaque but the reduction mechanism is largely unknown. The main
      aim of the present study was to determine whether the xylitol-induced reduction
      in the amount of plaque and the number of mutans streptococci could be
      demonstrated in subjects with (presumably) high levels of xylitol-resistant (XR;
      not inhibited by xylitol) mutans streptococci acquired following previous xylitol
      consumptions. 37 healthy dental students participated in the double-blind study.
      All subjects had been uncontrolled, habitual consumers of xylitol-containing
      products for at least 1 yr before the study. A 1-month washout period was
      followed by a 2-week test period during which either xylitol, xylitol-sorbitol or
      unsweetened chewing gum base was chewed 3-5 x a day. Plaque and saliva samples
      were collected at baseline and at the 2-week point for determination of the
      amount of plaque, microbiological variables, and hydrolytic enzymes. Mixtures of
      xylitol and sorbitol seemed to perform equally well with respect to reduction in
      the amount of plaque but not the number of mutans streptococci. Thus, polyols
      were the active ingredients of chewing gums able to modulate the amount of plaque
      and its microbial composition. Xylitol reduced plaque with a mechanism which
      appeared not to be associated with the study-induced changes in the proportion
      (%) of mutans streptococci in plaque, the number of salivary mutans streptococci,
      the proportion of XR strains in plaque or saliva, or the hydrolytic enzyme
      activities of plaque.

PMID- 9151072
TI  - Resin bonding to enamel and dentin with one-component UDMA/HEMA adhesives.
AB  - The aim of this study was to investigate the potential of UDMA/HEMA mixtures as
      priming and sealing components of dental adhesives. The monomers were mixed in
      weight ratios 100/0, 80/20, 60/40, 50/50, 40/60, 20/80, 10/90, and 0/100, light
      activated, and dissolved in acetone at equal parts. The 60/40 UDMA/HEMA mixture
      served as a reference which was modified with 5, 10, 20, and 30 parts 4-MET
      relative to the mass of the basic monomer mixture. Shear bond strengths (24 h) of
      resin composite cylinders, bonded with the adhesive monomers on human enamel and
      dentin, were determined following a total etch technique with phosphoric acid and
      application of the adhesives in 2 coats on moist tooth surfaces. Average bond
      strength to enamel was 32 MPa with no difference between the adhesives. On
      dentin, significantly different bond strengths were found between UDMA (12.9 MPA)
      and HEMA (19.4 MPa), whereas all binary mixtures' bond strengths were not
      significantly different (mean 16.2 MPa). Addition of 5 to 20 wt% 4-MET resulted
      in a significantly increased mean shear bond strength of 22.3 MPa on dentin. At
      10%, a maximum mean strength of 25.4 MPa was recorded. It is concluded that
      mixtures of commonly used polymerizable monomers, characterized by hydrophilic
      moieties and dissolved in acetone, are promising candidates for effective resin
      bonding to enamel and dentin, provided application by the moist bonding
      technique.

PMID- 9151074
TI  - Effects of division of attention during encoding and retrieval on age differences
      in episodic memory.
AB  - This study examined the effects of dual task requirements on age differences in
      free recall performance. One thousand adults ranging in age between 35 and 80
      years performed a word recall task alone and concurrently with a card-sorting
      task (at encoding, retrieval, or both). Age differences in memory performance
      were substantial under single task conditions, but after correcting memory
      performance under dual task conditions for differences in single task
      performance, age did not predict performance. These results do not support the
      hypothesis that reduced attentional capacity in old age is underlying age
      differences in episodic memory.

PMID- 9151073
TI  - Adult age differences in long-term semantic priming.
AB  - Young and older adults were first asked to decide if a list of individually
      presented words were "living" (e.g., "tree") or "nonliving" (e.g., "store"). This
      was termed the "orienting task." Next, subjects performed a pronunciation task.
      Semantic priming for young and older adults was indexed by determining if
      semantic congruence between words in the orienting task and words in the
      pronunciation task improved performance on the pronunciation task relative to
      pronounced words from semantic categories not primed in the orienting task. The
      present data, from two different experiments, revealed that subjects pronounced
      high-dominance exemplars of the "living" words primed in the orienting task
      faster than words not primed in the orienting task. These data indicated that
      semantic priming for relatively long prime-target stimulus onset asynchronies can
      occur, and that such priming is at least as robust for older adults as for young
      adults. The results are discussed in terms of four current models of semantic
      priming.

PMID- 9151075
TI  - Sustained attention and aging: overcoming the decrement?
AB  - A literature review found equivocal evidence of a performance decline at
      senescence on sustained attention (vigilance) tasks. The strongest evidence for
      such age effects was from Parasuraman and Giambra (PG; 1991). It was hypothesized
      that reduced perceptual and information-processing abilities of older adults
      (i.e., non-sustained attentional components of the task) were responsible for the
      age effects reported by PG and that such outcomes could be eliminated or reduced
      by minimizing the influence of those components. In Tasks 1 (n = 457) and 2 (n =
      427), which used PG's procedure and stimulus conditions, age effects on detection
      accuracy and on the detection time decrement were not found. False alarms were
      significantly greater in the old group than in the young group. In Task 3 (n =
      417), which minimized non-sustained attention components, some marginal evidence
      of age effects emerged. Potential explanations of these outcomes, such as an
      extremely small age effect, sampling bias, power differences, and undetected
      visual difficulties are considered, and further manipulations and controls are
      proposed.

PMID- 9151076
TI  - Effects of retention interval length on young and elderly adults' memory for
      spatial information.
AB  - Adult age differences in spatial memory following retention intervals of various
      lengths were examined in 47 young and 56 elderly subjects who recalled spatial
      information following either a 3-, 15-, or 30-min retention interval. The elderly
      adults were significantly less accurate than the young adults following the 30
      min retention interval only; there was no statistically significant effect of age
      at the 3-min and 15-min retention intervals. It is concluded that younger adults
      experience greater temporal stability of spatial memory than do older adults, and
      the relevance of the present findings for Craik's environmental support
      hypothesis is discussed.

PMID- 9151077
TI  - Isometric pinch force control and learning in older adults.
AB  - The learning of a dynamic isometric pinch force task was investigated in young
      adults (aged 19 to 29 years) and older adults (aged 64 to 75 years) through use
      of a visuo-motor tracking paradigm. Both groups significantly improved
      performance over trials, retained what was learned 1 week later, successfully
      transferred to a new target, and demonstrated interlimb transfer of training
      effects, reflecting a strong central component to this task that is apparently
      intact in older adults. However, performance differences between the two groups
      remained throughout the trials. Although it appeared that older adults were able
      to utilize a model-based strategy to predict the target path, as evidenced by
      minimal response lag, their absolute performance was inferior to that of young
      adults relative to an overall root mean square error score, a correlation
      coefficient, and their increased use of high-frequency components in the tracking
      signal. The age-related performance differences may be attributable to a
      peripheral decrement in tactile sensibility and/or muscle reorganization as well
      as a slowness in processing afferent information.

PMID- 9151078
TI  - Chromosomal anomalies as a predisposing factor for male infertility.
AB  - A "genetic factor" can be the reason for about 20% of male infertility cases.
      This could be due to chromosomal aberrations in sperm with immediate effect on
      conception or may result in recurrent spontaneous abortions of paternal origin.
      Techniques for the analysis of sperm chromosomal aberrations are still far from
      ideal. Sperm penetration to zona-free hamster oocytes and random in situ
      hybridization with sperm DNA using a range of fluorescent probes--are currently
      under investigation. Sperm chromosome analysis was performed in three distinct
      subgroups, (a) healthy, fertile individuals, (b) healthy but infertile subjects,
      and (c) carriers of chromosomal aberrations in lymphocytes. Sperm chromosomal
      aberrations occur in normal and fertile population in range from 1.9% to 15.8%.
      The aberrations are concerned both with number and structure of chromosomes. In
      infertile individuals, the main chromosome aberrations observed were
      translocations and pericentric inversions. Several hypotheses are also described
      indicating possible reasons for subfertility due to chromosomal anomalies. There
      are few gene families that can be involved in the regulation of spermatogenesis,
      mainly located on the Y-chromosome. Identification of defective gene(s) may lead
      to novel therapeutic strategies for infertility treatment.

PMID- 9151079
TI  - Influence of leukemia inhibitory factor (LIF) on the survival, proliferation and
      differentiation of human erythroid progenitor cells. In vitro studies under serum
      free conditions.
AB  - Different inflammatory cytokines are involved in the pathogenesis of the anemia
      of chronic disease (ACD), by inhibiting the proliferation of erythroid
      progenitors. Leukemia inhibitory factor (LIF), is an important inflammatory
      cytokine, and the purpose of this study was to evaluate its effect on the
      proliferation and viability of human erythroid progenitors. We have found that
      LIF slightly increased the survival of human early progenitor cells cultured
      under serum free conditions. LIF also slightly costimulated in vitro growth of
      human erythroid colonies. This last effect seems to be a direct one, because we
      found that LIF receptor (LIF-R) is expressed in cells isolated from growing in
      vitro human erythroid BFU-E colonies. These data, and the data reported by others
      in in vivo models, where LIF administration to experimental animals did not
      change the values of erythropoietic parameters, demonstrate that this
      inflammatory cytokine itself is not involved in the pathogenesis of ACD.

PMID- 9151080
TI  - Transformation of a human mixed GH-PRL adenoma cell population in response to
      long-term bromocriptine treatment.
AB  - A child was operated 3 times because of a recurrent growth hormone- and prolactin
      producing pituitary adenoma. Between the operations she was treated for five
      years with bromocriptine. The characteristics of the tumour cell population
      collected after the last operation was now examined by electron microscopy,
      immunocytochemistry, and in tissue culture and compared to those of the primary
      tumour cells reported earlier. A prominent change was the reversal of the
      proportion of the densely and sparsely granulated cells in favour of the GH-type,
      densely granulated cells. These cells, some of them coexpressing PRL, did not
      essentially change their characteristics either in vivo or in culture. On the
      other hand, pleomorphous cells with smaller cytoplasmic area and prominent
      lysosomal structures represented the sparsely granulated population containing
      PRL or both PRL and GH. The morphological alteration of the PRL-type cells was
      also reflected in vitro. Hence, while GH-type cells prevail, at least a sub
      population of PRL-type cells survives long-term bromocriptine administration. A
      shift in the incidence of the two cell types in favour of the GH-type cells
      explains the change in the endocrine status of the patient.

PMID- 9151081
TI  - The correlation between NK cytotoxic activity and the production of the
      proinflammatory cytokines during the ageing process.

PMID- 9151082
TI  - 26 kD TNF alpha precursor molecule and 17 kD mature TNF alpha form differentiate
      the clinical status of the patients with long-standing diabetes mellitus of type
      I.

PMID- 9151083
TI  - Soluble and membrane bound IL-2 receptors (alpha and beta chains) in chronic
      hemodialyzed patients.

PMID- 9151084
TI  - BAL-isolated cells after administration of mutein VI rhTNF-alpha into Morris
      hepatoma.

PMID- 9151085
TI  - Ultrastructural analysis of pulmonary capillaries after mutein VI rhTNF-alpha
      administration into Morris hepatoma.

PMID- 9151086
TI  - The effect of rhTNF-alpha on morphology of placenta in pregnant rabbits.

PMID- 9151087
TI  - The effect of danazol on the activity of peritoneal macrophages.

PMID- 9151088
TI  - Effects of eicosanoids secreted by stimulated Kupffer cells on isolated rat
      hepatocytes.

PMID- 9151089
TI  - The influence of testicular and peritoneal macrophages on Leydig cell secretory
      function in co-culture.

PMID- 9151090
TI  - Immunocytochemical localization of interleukin-1 (IL-1) in testicular macrophages
      and Leydig cells of the bank vole (Clethrionomys glareolus, S.).

PMID- 9151091
TI  - The effect of IL-1 on basal and hCG-stimulated testosterone secretion by Leydig
      cells of the bank voles (Clethrionomys glareolus, S.).

PMID- 9151092
TI  - Investigation on apoptosis in Leydig cells cultured in vitro.

PMID- 9151093
TI  - Topography of the changes of free calcium ions due to steroid hormone action on
      human spermatozoa.

PMID- 9151094
TI  - Immunohistochemical localization of androgen receptor (AR) in rat ovary.

PMID- 9151095
TI  - Studies on mechanisms of steroid hormone action on thymus stromal cells.

PMID- 9151096
TI  - Immunocytochemical investigations of the thyroid gland of guinea pig in histamine
      shock.

PMID- 9151097
TI  - Solid cell nests (SCN) in the thyroid gland of some laboratory and wild mammals:
      histochemical and preliminary immunocytochemical studies.

PMID- 9151098
TI  - The significance of the immunocytochemical investigations in diagnosis and
      prognosis of pituitary adenomas.

PMID- 9151099
TI  - Ultrastructural investigations on the guinea pig parotid glands after application
      of exogenous histamine.

PMID- 9151100
TI  - Morphobiochemical studies on alpha-amylase secretion by pancreatic follicles of
      guinea pigs after the application of exogenous histamine.

PMID- 9151101
TI  - Effect of different fluorine doses on the supraoptic nucleus of the rat.

PMID- 9151102
TI  - On the spatial organization of ubiquitin-dependent proteolysis in HeLa cells.

PMID- 9151103
TI  - The culture of human keratinocyte. Immunocytochemical and ultrastructural assays
      of proliferation and differentiation.

PMID- 9151104
TI  - Evaluation of laminin and cytokeratin-10 expression in squamous cell carcinoma of
      the skin.

PMID- 9151105
TI  - Fibrous connective tissue of rat binds anti-immunoglobulin antibodies.

PMID- 9151106
TI  - Histochemical investigations of the skeletal muscle fibres during the reversed
      passive Arthus reaction in guinea pigs.

PMID- 9151107
TI  - The tetraploidy of Purkinje cells in the cerebellum in reference to the problem
      of polyploidy.

PMID- 9151108
TI  - Computerized analysis of cytochemical reactions of spermatozoa in rats
      chronically treated with lead acetate [Pb(II)].

PMID- 9151109
TI  - Three-dimensional reconstruction by confocal laser scanning microscopy in routine
      pathologic specimens of benign and malignant lesions of the human breast.
AB  - Confocal laser scanning microscopy (CLSM) has become an exciting new instrument
      because of its increased resolution over conventional wide-field microscopy and
      its high performance three-dimensional (3D) optical sectioning. Although CLSM has
      been used extensively in cell biology, few applications have been reported in
      routine clinical pathology. In this study, 3D reconstruction was performed on
      routine formalin-fixed, paraffin-embedded tissues of normal mammary duct, simple
      ductal hyperplasia, intraductal papillary hyperplasia, ductal carcinoma in situ,
      invasive carcinoma, and lymph node metastatic carcinomas of the human breast by
      using computer-assisted CLSM in conjunction with a 3D reconstruction software
      package (microVoxel). The selected specimens were sectioned at 30 microns,
      mounted on glass slides, and stained with the DNA fluorescent probe, YOYO-1
      iodide. The nuclear DNA and chromatin texture were clearly demonstrated after
      pretreatment with RNAase and hydrolysis with 2 N HCl. High quality 3D images were
      obtained by processing the optical section stacks with volume render and surface
      display parameters in microVoxel. 3D morphologic characteristics of different
      breast lesions were examined in various orientations by angular image rotation.
      The clearly benign lesions (simple ductal hyperplasia and intraductal papillary
      hyperplasia) revealed similar 3D morphologic features, including: (1) smooth
      nuclear surface and homogeneous chromatin fluorescence intensity; (2)
      hyperplastic cell nuclei showing similar shape and volume; and (3) clearcut
      margin of basement membrane defined by spindle-shaped myocytes of the ductal
      outer layer. In contrast, carcinomas displayed remarkably different features in
      3D morphology, including: (1) irregular nuclear surface: (2) marked nuclear
      pleomorphism (irregular, angulated and indented shape of nuclear volume); (3)
      irregular and coarse chromatin texture; (4) chaotic arrangement of tumor cell
      nuclei; and (5) absence of myocytes, indicating no clear margin at the site of
      infiltration of cancer cells. In conclusion, nuclear structure, specifically
      demonstrated by CLSM of YOYO-1 iodide fluorescently stained cells, used in tandem
      with 3D volume morphologic reconstruction, may provide a useful research
      diagnostic tool in pathology.

PMID- 9151110
TI  - Changes in osteopontin mRNA expression during phenotypic transition of rabbit
      arterial smooth muscle cells.
AB  - Transition from a contractile to a synthetic phenotype appears to be an early key
      event during the development of intimal thickening after arterial wall injury. We
      examined the expression of osteopontin mRNA, proliferation, and phenotypic
      properties of smooth muscle cells (SMCs) in rabbit neointima after balloon
      denudation and in primary culture. A strong osteopontin mRNA signal was detected
      in the thickened intima 1 week after balloon denudation and in the surface layer
      of the intima 2 weeks after balloon denudation. Ki-67 immunohistochemistry showed
      that osteopontin mRNA expression increased when SMCs entered the proliferating
      phase in the intima. Rabbit arterial SMCs on type I collagen after 1 day of
      primary culture with growth factors, as well as freshly isolated cells, were in
      the G0 phase (contractile phenotype) and did not express osteopontin mRNA. After
      3 days of culture, most cells entered the G1B phase (synthetic phenotype) and
      expressed osteopontin mRNA. In the absence of growth factors, most cells
      transferred to the G1A phase (intermediate phenotype) after 3 and 7 days, but did
      not express osteopontin mRNA. Our findings indicate that the osteopontin gene
      provides a marker that can be used to distinguish the phenotypic properties of
      vascular SMCs.

PMID- 9151111
TI  - Hyaluronan and chondroitin sulfate proteoglycans are colocalized to the ciliary
      zonule of the rat eye: a histochemical and immunocytochemical study.
AB  - In previous studies, chondroitin sulfate proteoglycans have been localized to the
      periphery of the zonular fibers and the individual zonular fibrils (or
      microfibrils) after Cuprolinic blue staining in conjunction with chondroitinase
      digestions and immunogold labelling with 2-B-6 antibody. In the present study, we
      wished to determine if these proteoglycans are linked to hyaluronan to form a
      large multimolecular aggregate. To accomplish this, we localized the hyaluronan
      using a biotinylated hyaluronan-binding protein fragment of chondroitin sulfate
      proteoglycan, containing also the link protein, purified from bovine nasal
      cartilage. The results showed that the ciliary zonule of the rat eye was reactive
      with the biotinylated hyaluronan-binding probe as demonstrated by streptavidin
      peroxidase-diaminobenzidine staining and streptavidin-gold labelling. Hyaluronan
      gold labelling showed that the gold particles were mostly localized on the
      periphery of the zonular fibers, which was similar to the localization pattern of
      the zonule associated-proteoglycans. This hyaluronan-binding probe also strongly
      labelled the sites of zonule insertion over the basement membrane of the inner
      ciliary epithelium at the pars plana and the lens capsule at the equatorial
      region, which suggests its probable role in the attachment of ciliary zonule to
      the basement membranes. To demonstrate whether these two molecules are linked to
      one another, ultrastructural colocalization of both hyaluronan and chondroitin
      sulfate proteoglycans was performed on the same sections by double-gold
      labelling, and combined Cuprolinic blue staining and hyaluronan-gold labelling.
      Gold particles of 15 and 10 nm in sizes labelling both hyaluronan and chondroitin
      4-sulfate, were colocalized to the surface of the zonular fibers. The combined
      Cuprolinic blue staining and hyaluronan-gold labelling showed that the gold
      particles were localized towards the ends of the Cuprolinic blue-stained rodlets,
      which strongly suggests that these chondroitin sulfate proteoglycans are linked
      to the hyaluronan chain to form a large aggregate surrounding the periphery of
      the zonular fibers. These ciliary zonule-associated proteoglycan-hyaluronan
      aggregates may play a role in organizing the individual zonular fibrils
      (microfibrils) into bundles of zonular fibers.

PMID- 9151112
TI  - Ultrastructural immunolocalization of polyamines in HeLa cells subjected to fast
      freezing fixation and freeze substitution.
AB  - Polyamines have been localized at the ultrastructural level in HeLa cells
      subjected first to fast-freezing fixation (FFF)-freeze substitution (FS) and then
      to an immunocytochemical method combining anti-polyamine antibodies and
      immunogold labelling. Polyamines were found in both the cytoplasm and the nucleus
      and, in the latter, particularly over the dense chromatin area. To our knowledge,
      this is the first example of the electron microscopic localization of a hapten
      after FFF-FS. For the preservation of fine ultrastructural details, this FFF-FS
      method is not only adequate but also greatly reduces, if not totally eliminates,
      any leeching-out and redistribution of the polyamines during the preparation of
      the sample. For the preservation of antigenicity in situ during FS, epoxy resin
      was more effective than hydrophilic LR white resin, probably due to the
      solubility of polyamines in the latter.

PMID- 9151113
TI  - Localization of vitronectin in the normal and atherosclerotic human vessel wall.
AB  - Vitronectin (Vn) regulates proteolytic enzyme systems, as well as cell migration
      and tissue remodelling. These processes have been implicated in the pathogenesis
      of atherosclerosis. In this study, the distribution of Vn antigen in apparently
      normal and atherosclerotic human blood vessels was evaluated. Normal and diseased
      vessels showed Vn immunostaining in the lamina elastica interna and externa, and
      in strand-like structures in the adventitia. In most of these instances, the Vn
      antigen appeared to be located in the proximity of elastin. In pulmonary
      arteries, Vn staining was additionally detected in the media. The intima was
      devoid of Vn antigen in all vessels studied. In general, there was increased
      deposition of Vn antigen in the atherosclerotic arteries. In particular, strong
      Vn staining was apparent in amorphous material adjacent to cholesterol clefts and
      in acellular fibrous tissue, in plaques present in the carotic artery and aorta.
      Collagen layers and fresh fibrin depositions were devoid of Vn antigen. In spite
      of the abundance of Vn immunostaining throughout the normal and diseased vessel
      wall, the Vn transcript was not detectably by in situ hybridization. These
      results indicate that Vn is a constituent of the normal vessel wall and raise the
      possibility that increased local deposition of Vn may be related to the
      development of atherosclerotic vascular disease.

PMID- 9151114
TI  - Lectin-binding glycoconjugates in Paramecium primaurelia: changes with cellular
      age and starvation.
AB  - Lectins with different sugar specificities and binding to phagosome-lysosome
      systems as well as cell surface constituents were used to study glycoconjugate
      variation throughout culture and clonal life in Paramecium primaurelia,
      particularly during the transition period from logarithmic to stationary growth
      phase and in relation to clonal decline, respectively. These lectins include
      Griffonia simplicifolia agglutinin II (GS II), Ricinus communis agglutinin
      (RCA120). Arachis hypogea agglutinin (PNA), succinyl concanavalin A (succinyl-con
      A), and Triticum vulgaris agglutinin (WGA). The labeling obtained varies both
      according to the lectin used and to the culture and clonal age of the cells.
      Negative results were obtained in logarithmic growth phase cells and in clonal
      young cells by using lectin GS II. Conversely, lectins RCA120 and PNA bind to the
      cell surface, the oral region as well as cilia, and do not undergo modifications
      with culture or clonal age and after permeabilization. WGA binds to constituents
      of the cell surface, trichocyst tips, food vacuoles, the oral region, and cilia
      but the extent of labeling decreases as culture age increases; during clonal
      decline, cells show the same labeling pattern as starved cells. Finally, the
      lectin succinyl-con A shows a large amount of binding sites on the cell surface,
      on trichocyst tips, and in the oral region of logarithmic-phase cells, whereas
      the number of sites decreases in late stationary phase. The data obtained partly
      differ from those reported in the literature and the differences can be
      attributed to the culture conditions and species examined. Nevertheless, the
      assumption that a rearrangement of some glycoconjugates of membrane throughout
      culture and clonal life of Paramecium is confirmed.

PMID- 9151115
TI  - Nuclear ribonucleoprotein-containing structures undergo severe rearrangement
      during spontaneous thymocyte apoptosis. A morphological study by electron
      microscopy.
AB  - The rearrangement of nuclear ribonucleoprotein (RNP)-containing structures during
      spontaneous thymocyte apoptosis has been investigated by electron microscopy.
      Along with chromatin margination and condensation. RNPs segregate into the
      central portion of the nucleus, in the form of heterogeneous clusters of granules
      which contain interchromatin and perichromatin granules, perichromatin fibrils,
      nucleolar components, and probably coiled bodies. In parallel with progressive
      chromatin condensation and karyorrhexis, granule clusters are then extruded into
      the cytoplasm and are finally released at the cell surface as membrane-bound
      cytoplasmic debris, sometimes in association with apparently undamaged organelles
      such as centrioles. It is likely that this RNP segregation may correlate with a
      severe impairment of protein synthesis. A similar phenomenon was observed in
      elongating spermatids, when transcriptional arrest is induced during the process
      of reversible silencing of the male genome. It may be hypothesized that
      segregation into heterogeneous granule clusters could be a common mechanism to
      remove redundant RNP-containing structures from the cell.

PMID- 9151116
TI  - Distinct subcellular localization of beta-tubulin epitopes in the adult mouse
      brain.
AB  - A panel of monoclonal antibodies specific of alpha-tubulin (TU-01, TU-09) and
      beta-tubulin (TU-06, TU-13) subunits was used to study the location of N-terminal
      structural domains of tubulin in adult mouse brain. The specificity of antibodies
      was confirmed b immunoblotting experiments. Immunohistochemical staining of
      vibratome sections from cerebral cortex, cerebellum, hippocampus, and corpus
      callosum showed that antibodies TU-01, TU-09, and TU-13 reacted with neuronal and
      glial cells and their processes, whereas the TU-06 antibody stained only the
      perikarya. Dendrites and axons were either unstained or their staining was very
      weak. As the TU-06 epitope is located on the N-terminal structural domain of beta
      tubulin, the observed staining pattern cannot be interpreted as evidence of a
      distinct subcellular localization of beta-tubulin isotypes or known post
      translational modifications. The limited distribution of the epitope could,
      rather, reflect differences between the conformations of tubulin molecules in
      microtubules of somata and neurites or, alternatively, a specific masking of the
      corresponding region on the N-terminal domain of beta-tubulin by interacting
      protein(s) in dendrites and axons.

PMID- 9151117
TI  - The expression of sf-1/Ad4BP is related to the process of luteinization in the
      marmoset (Callithrix jacchus) ovary.
AB  - Expression of the nuclear receptor, steroidogenic factor-1 (SF-1/Ad4BP), was
      studied in a primate (marmoset) ovary using immunohistochemical, RT-PCR, and
      immunoblot techniques. The periovulatory phase was compared with the luteal
      phase. With PCR we found a marmoset homolog of SF-1/Ad4BP to be expressed in
      ovarian and other steroidogenic tissues. Characteristically, the periovulatory
      ovaries consisted of growing (non-luteinized) small follicles together with large
      luteinizing follicles and many corpora lutea accessoria (Clas), which had
      developed from atretic large follicles. During the luteal phase, true corpora
      lutea (Cls) were additionally found. In general, we found that small follicles
      were devoid of any immunoreactivity of SF-1/Ad4BP. In large follicles, the
      luteinizing theca and granulosa cells express SF-1/Ad4BP. All luteal cells of
      Clas showed a nuclear staining in both ovary types. In Cls, only a few luteal
      cells were positive. Large follicles of different sizes showed no differences in
      expression level, as evidenced by immunoblot analysis. Our results indicate that
      SF-1/ Ad4BP participates in the activation of genc transcription during the onset
      of luteinization and that Clas are essential for ovarian luteal function.

PMID- 9151118
TI  - Localization of regulatory peptides in the male urogenital apparatus of domestic
      equidae: a comparative immunohistochemical study in Equus caballus and Equus
      asinus.
AB  - An immunohistochemical study was carried out on specimens of testis, excurrent
      duct including the male accessory glands and urethra in its various tracts in the
      horse and the donkey, in order to localize nine regulatory peptides.
      Immunoreactivities were tested by means of Labelled Strept Avidin-Biotin (LSAB)
      method. The study has shown that Equine male genitalia are supplied by many
      peptide immunoreactive nerves containing NPY-, VIP-, leu- and met-Enkephalin-,
      Substance P-, CGRP- and Bombesin/GRP-like peptides, each of them having a
      characteristic distribution pattern. These neurotransmitters were localized in
      nerve fibers running in the connective tissue or in contact with the smooth
      muscle cells, as well as in sub- and intraepithelial nerve terminals, and in
      perivascular nerve fibers. In addition, leu- and met-Enkephalin-like
      immunoreactive endocrine cells were shown in the bulbourethral gland of the
      horse. In both species it was evident that an extensive utilization of NPY and
      VIP exists. A contingent of NPY- and VIP-ir nerve fibers may have an intrinsic
      origin. The other regulatory peptides tested show a characteristic distribution
      pattern, limited to some organs and peculiar to each of the two species of
      Equidae. Differences observed comparing E. caballus and E. asinus might be
      related to the species-specific balance of the accessory neurotransmitters which
      in turn accompany adrenergic innervation. In both species it is noteworthy the
      complete absence of any regulatory peptide in the testis, with the exception of
      the perivascular localization of NPY-ir nerve fibers.

PMID- 9151119
TI  - Comparative stereological study on zonation and cellular composition of adrenal
      glands of normal and anencephalic human fetuses. I. Zonation of the gland.
AB  - Comparative stereological studies were performed on zonation of adrenal glands in
      10 anencephalic and 11 normal fetuses, aged between 24 and 39 postovulatory
      weeks. The development of adrenal fetal zone (FZ) is the main factor responsible
      for normal adrenal gland growth during the intra-uterine life. At the end of
      fetal period volume of this zone attains over 8200 mm3 and constitutes 69-70% of
      the total gland volume, while respective values for zona glomerulosa (ZG), zona
      fasciculata (ZF) and medulla (M) are 1665 mm3 (14%), 833 mm3 (7%) and 1071 mm3
      (9%). These data were in striking contrast with those found in adrenals of
      anencephalic fetuses, in which volume of the gland attained only ca 35% of that
      in normal fetuses. In the oldest anencephalic fetus studied (39 weeks) the volume
      of the fetal zone was 962 mm3 (ca 8-folds lower than in normal fetus) comprising
      only 25% of the total gland volume. For the remaining zones the values were: ZG
      1501 mm3 (ca 90% of the normal value and 39% of the total gland volume); ZF-770
      mm3 (ca 92% and 20% respectively), and M-539 mm3 (ca 50% and 14%, respectively).
      This stereological study provides the first systemic description of the
      development of adrenal gland of anencephalic fetuses in comparison with the
      normally developing gland. Moreover, evidence is given that the growth of adrenal
      medulla is also retarded in anencephaly while the growth of the zona glomerulosa
      remains rather unaffected.

PMID- 9151120
TI  - The alveolar type II cell is a pluripotential stem cell in the genesis of human
      adenocarcinomas and squamous cell carcinomas.
AB  - Studies in a canine bronchogenic carcinoma model indicate that alveolar type II
      cells may differentiate from carcinogen-exposed epithelium of larger bronchi and
      generate adenocarcinomas with bronchioloalveolar and other growth patterns. In
      this study, we investigated whether type II cells are one of the major
      proliferating cells (= stem cells) in the genesis of two major subsets of
      bronchogenic carcinoma in humans. Adenocarcinomas (17 bronchioloalveolar; 3
      papillary; and 10 other) and squamous cell carcinomas (n = 27) as well as
      (pre)neoplastic lesions in adjacent bronchi and bronchioles were examined for the
      presence of type II cell markers and cellular proliferation markers (PCNA; Ki-67)
      using light and electron microscopy and immunohistochemistry. Distinctive
      features of type II cells, which do not depend upon the degree of cell maturity,
      are the approximately cuboid shape, large and roundish nucleus, cytoplasmic
      staining for surfactant protein A (SP-A), and presence of multilamellar bodies or
      their precursory forms. Cells with this phenotype were found in early progressive
      (i.e., dysplastic, in situ, microinvasive) lesions in conducting airways and in
      all the carcinomas investigated, although with a much greater abundance among
      glandular lesions compared to squamous lesions. The most consistent sites of type
      II cells were the basal and adjacent epithelial layers. Nuclear PCNA (Ki-67)
      expression usually predominated in the same region. None of the lesions displayed
      specific Clara cell features. Our findings strongly suggest that the type II cell
      is a pluripotential stem cell in human lung carcinogenesis. Based on our findings
      in humans and dogs, we postulate that type II tumor stem cells may originate from
      one of two sources: (1) normal bronchial epithelium (by an oncofetal mechanism of
      differentiation); and (2) normal alveolar type II cells.

PMID- 9151121
TI  - Analysis of allogenic lymphocytes in rat thymus following sublethal irradiation.
AB  - The effects of allogeneic lymphocytes on the rat thymus following sublethal
      irradiation were investigated using immunofluorescence. The recovery of thymus
      weight following irradiation was delayed in rats 6 days after receiving
      lymphocytes compared to controls. Allogeneic cells forming colonies were detected
      by immunofluorescence in both the cortex and medulla of the host thymus, most
      frequently on day 15 when an appropriate number (3 x 10(6)) was injected. The
      allogeneic cells detected in the host thymus, presumably T lymphocytes, appeared
      to disturb thymic reconstitution following irradiation. However, double
      immunofluorescence staining revealed that allogeneic cells did not affect the
      thymic stromal microenvironment. Allogeneic cells may have subsequently affected
      thymic tissue via cytokines. It is important to investigate not only the
      character of allogeneic cells in the host thymus but also the interactions of
      donor allogeneic cells, host immature lymphocytes and thymic epithelial cells
      because of the possibility that these allogeneic cells in the host thymus could
      prevent the rejection of allogeneic transplants.

PMID- 9151122
TI  - Ultrastructural changes in the synthetic and secretory patterns of pulmonary
      surfactant following pilocarpine in vivo.
AB  - Previous studies have demonstrated that the muscarinic agonist pilocarpine
      stimulates the secretion of pulmonary surfactant from mammalian alveolar type II
      cells. The results of the present study quantify, via ultrastructural stereologic
      analysis, this response through 24 hours. The cytoplasmic volume density of
      lamellar bodies decreases significantly at 0.5 and 4 hours post-injection. This
      value is increased significantly at 12 hours post-injection. Elements of the
      secretory apparatus increase significantly at many of the post-injection times.
      At 12 hours post-injection many of the type II cells are quite laden with
      lamellar bodies, with some appearing surprisingly large. This may be a useful
      model for continued study of the relationship between synthesis and secretion of
      pulmonary surfactant.

PMID- 9151123
TI  - Membrane skeletons in avian erythrocytes as revealed by the quick-freezing and
      deep-etching method.
AB  - Ultrastructure of chicken erythrocytes were examined by the quick-freezing and
      deep-etching (QF-DE) method. Some erythrocytes were fixed with paraformaldehyde
      and prepared with erythrocyte-splitting method or saponin treatment to remove
      soluble proteins before quick-freezing. Others were prepared in the cytosol
      buffer with the erythrocyte-splitting method to obtain natural state of
      cytoskeletons. Non-expanding membrane skeletons were highly condensed on the
      cytoplasmic side of lipid membrane in the paraformaldehyde-fixed specimens. Under
      unilateral extension of the specimens, long stretched filaments were connected
      alternately with condensed filamentous or granular structures under erythrocyte
      membranes. As the membrane skeletons got closer to the marginal bands, they
      become more dense network structures. Moreover, in the fresh unfixed specimens,
      dense networks of filaments were localized underlying erythrocyte membranes in a
      relatively intact state. Fine filaments connected the marginal microtubule bands
      to the cytoplasmic sides of erythrocyte membranes. The different distribution of
      each cytoskeletal component and the association of these structures may support
      the elliptocytic shape of chicken erythrocytes and resist the dynamic
      circumstance.

PMID- 9151124
TI  - Endotheliitis-like changes in chronic hepatitis C.
AB  - Liver biopsies in hepatitis C frequently show bile duct damage, lymphoid
      follicles, large and small droplet fat, hepatocyte multinucleation. Mallory body
      like material, and activation of sinusoidal inflammatory cells. Even though these
      lesions are useful parameters in the diagnosis of hepatitis C, their specificity
      remains uncertain. Endotheliitis-like changes of small portal veins have been
      described for various liver diseases, including viral hepatitis. The aim of the
      present study was to investigate the prevalence and severity of endotheliitis
      like changes in chronic hepatitis C in comparison with chronic hepatitis B. For
      this purpose, liver biopsies of 50 patients with chronic hepatitis C and 48
      patients which chronic hepatitis B were systematically analyzed for the presence
      of endotheliitis-like changes. Endotheliitis-like changes were defined as
      lymphocytic infiltration of venous walls, subendothelial lymphocyte accumulation,
      adherence of lymphocytes to the endothelium, and endothelial cell damage.
      Endotheliitis-like change severity was graded (borderline/questionable; slight to
      moderate; severe), and endotheliitis-like changes were analyzed in small portal
      veins and in central veins. Endotheliitis-like changes were significantly more
      frequent in chronic hepatitis C than in chronic hepatitis B (41.5% vs. 6.9%; p <
      0.05). In chronic hepatitis C, endotheliitis-like changes predominated in small
      portal veins, but 27% of small hepatic veins were involved as well. The findings
      indicate that endotheliitis-like changes may represent a useful histological
      parameter in the diagnosis of chronic hepatitis C.

PMID- 9151125
TI  - Hepatocyte apoptosis in hepatic iron overload diseases.
AB  - In this retrospective study, we systematically analyzed hepatocyte apoptosis in
      three situations of hepatic iron overload (hereditary hemochromatosis; hepatic
      iron overload of unknown reason; iron overload due to hyperhemolysis or exogenous
      iron administration). Apoptosis was assessed by use of DNA nick end-labelling.
      The results suggest that hepatic iron overload is associated with an increased
      apoptotic rate of hepatocytes, and that iron-laden hepatocytes in hemochromatosis
      behave, with respect to apoptosis, differently from those in other states of iron
      overload. The hepatocyte apoptotic rate tended to increase as a function of the
      degree of iron storage. As in other pathological liver changes studied so far, an
      elevated apoptotic rate of hepatocytes predominated in the pericentral parts of
      liver acini in hemochromatosis, but not in the two other groups of hepatic iron
      overload. Possible mechanisms for this difference are discussed, particularly
      with respect to a participation of the Kupffer cell system.

PMID- 9151126
TI  - Structural and ultrastructural study of the myocardium after 24-hour preservation
      in University of Wisconsin solution.
AB  - This study deals with myocardial preservation after 24 hours of continuous
      perfusion with University of Wisconsin (UW) solution, focusing on the
      morphological changes produced by preservation and reperfusion, and their
      possible relationship to the composition of the solution and the immediate
      hemodynamic findings after orthotopic heart transplantation in dogs. Following
      preservation, the histological images of the myocardium were normal in almost
      every case. After revascularization, although 50% of the hearts recovered
      preoperative functional levels, there were relevant histological changes in all
      of them. These changes consisted of interstitial edema, damage to at least 50% of
      the mitochondria, presence of contraction bands, loss of intercellular junction
      structure and vasoconstriction. According to these results, the association of
      continuous perfusion and UW solution appears to be effective during the ischemic
      period of prolonged myocardial preservation, but not during reperfusion. Perhaps
      the proportion of viable hearts could be increased by preventing
      vasoconstriction.

PMID- 9151127
TI  - The skin injury induced by high energy dose of ultraviolet in hairless
      descendants of Mexican hairless dogs.
AB  - Histopathological changes in the dorsal skin of hairless descendants of Mexican
      hairless dogs (MHDs) exposed to artificial irradiation with high energy dose (180
      kJ/m2) of ultraviolet (UV) rays (UVA + B) were investigated. Macroscopically,
      erythema and edema were observed in the irradiated skin at 1 day after
      irradiation (DAI), and blister formation occurred except one dog at 2 DAI.
      Erythema almost disappeared at 5 DAI, and at 6 DAI, the skin recovered to almost
      normal state. Light microscopically, sunburn cells were observed at 1 DAI. Then
      intercellular edema and blister formation in the epidermis and dermal edema were
      evident at 2 and 3 DAI. At 6 DAI, the skin showed almost normal features except
      for slight epidermal thickening, but melanin granules, which were distributed in
      almost the whole length of the epidermis before UV irradiation, were detected
      only in cells which seemed to be melanocytes except one dog.
      Dihydroxyphenylalanine (DOPA)-positive melanocytes almost disappeared at 1 and 2
      DAI, and at 6 DAI, the number of DOPA-positive melanocytes increased over the
      level before UV irradiation. The ultrastructural features of melanocytes were
      characterized by vacuolated cytoplasm, decreased melanosomes, irregular-shaped
      nuclei and shortened dendrites at 1 DAI, and returned to normal at 6 DAI. These
      findings of melanocytes reflect the severity of the skin injury and support weak
      suntan reaction in this case. In conclusion, severe form of UV-induced skin
      injury seen in humans could be reproduced in hairless descendants of MHDs exposed
      to high energy dose of artificial UVA + B.

PMID- 9151128
TI  - Comparative stereological studies on zonation and cellular composition of adrenal
      glands of normal and anencephalic human fetuses. II. Cellular composition of the
      gland.
AB  - In our previous paper (Bocian-Sobkowska et al., 1997) we demonstrated a striking
      difference in development of zonation in adrenals of normal and anencephalic
      human fetuses. The purpose of the present study was to characterize, by means of
      stereology, the cellular composition of developing adrenals in the same case.
      Studies were performed on 11 pairs of adrenal glands from normal fetuses and 10
      from anencephalic fetuses. In the studied period of development (24 to 39 weeks
      of intra-uterine life) the average volume of cells in normal glands increased as
      follows: zona glomerulosa (ZG) from 355 to 870 microns3; zona fasciculata (ZF)
      from 779 to 1200 microns3; fetal zone (FZ) from 2004 to 2380 microns3: and
      medulla (M) from 600 to 970 microns3. In anencephalic fetuses, the appropriate
      values were: ZG-380-680 microns3; ZF-460-680 microns3; FZ-1820-1680 microns3; and
      M-870-1400 microns3. At the end of the studied period the number of ZG cells in
      normal fetuses was two fold higher than in anencephalics, ZF cells-6-fold and in
      FZ-5-fold higher, while in the M the number of cells was nearly equal in both
      groups. During the whole investigated period of intra-uterine development the
      total number of adrenocortical cells in normal glands increased ca 2.5-fold,
      while in anencephalic glands only ca 0.5-fold, reaching at the end ca 40% of
      normal value. In both normal and anencephalic adrenals the number of ZG and M
      cells was highly correlated with ZG/M cell ratio, being slightly higher in normal
      glands. No such relation was demonstrated for cells of the remaining
      adrenocortical zones.

PMID- 9151129
TI  - Ultrastructural alterations of the cortical epithelial cells of the rat thymus
      after cyclophosphamide treatment.
AB  - A single dose of cyclophosphamide (CY) was administered to Sprague-Dawley rats to
      investigate the effects of CY on thymic cortical epithelial cells (TCE) at the
      ultrastructural level. The most striking finding among the alterations in the TCE
      after CY treatment was a cytoplasmic vacuolization with an increased amount of
      granular and membranous content. The granular content appeared not only as dense
      bodies but also as loosely aggregated forms or finely dispersed granules. The
      membranous structures appeared in various forms including vesicular, tubular,
      vacuolar and irregular membranous structures and myelin figures. Some of the
      membranous structures contained granular material. Several vacuoles were closely
      associated with the endoplasmic reticulum (ER). The morphological alterations of
      the ER were also remarkable. The Golgi apparatus, mitochondria and vesicles
      increased in number. The cytoplasm became densely granulated due to an increased
      number of ribosomes and an increased amount of granular material. The
      tonofilaments lost their original array and increased in amount. The cell surface
      exhibited many cytoplasmic processes like microvilli. It seems that the above
      features result not only from some damage by CY, but also signs of a
      hyperfunctional state of the TCE, probably due to their important functions in
      repopulation and maturation of the cortical thymocytes during recovery after CY
      induced acute thymic involution, including the secretion of some humoral factors.

PMID- 9151130
TI  - Estimation and comparison of the contents of blood group B antigens in selected
      human tissues by microphotometric quantification of Griffonia simplicifolia
      agglutinin I-B4 staining with or without prior alpha-galactosidase digestion.
AB  - Griffonia simplicifolia agglutinin I-B4 (GSAI-B4) has broader specificity for B
      antigen variants and can recognize the antigens in a wide variety of human
      tissues. Thus, the concentration range of GSAI-B4 required for staining and the
      susceptibility of staining to alpha-galactosidase digestion is presumed to
      correlate well with the density of B antigens in tissue sections. By
      microphotometric quantification of staining intensity at different concentrations
      of GSAI-B4 with or without alpha-galactosidase digestion, concentration of B
      antigens in selected tissues was evaluated and compared. Based on the present
      results and the previous ones of direct measurement of galactose of B antigens in
      sublingual glands and red blood cells (Ito et al., 1993), the order of
      concentration of B antigens in tissues examined was estimated as follows; mucous
      cells of sublingual glands from German nonsecretors < red blood cells and
      vascular endothelial cells (= 2.7 x 10(-3) nmole/cm2), thyroid papillary
      carcinomas and Hassall's corpuscles from nonsecretors < mucous cells of
      sublingual gland from Japanese nonsecretors < pancreatic acinar cells from both
      secretor and nonsecretors, Hassall's corpuscles and kidney collecting tubules
      form secretors < mucous cells of sublingual gland from secretors (> 8.5-11.7
      nmole/cm2) and mucous cells of Brunner's gland from nonsecretors < mucous cells
      of Brunner's gland from secretors. From the above estimation, it is apparent that
      the expression of B antigen in Brunner's gland is partly dependent on the
      secretor status of individuals and that Japanese nonsecretors secrete substantial
      amounts of B antigens from sublingual gland while German nonsecretors do not. The
      present results also revealed an unexpected staining behavior of GSAI-B4 in some
      tissues, i.e. in mucous cells of sublingual glands and collecting tubules of
      kidney from secretors, staining intensity was markedly depressed at higher
      concentration of the lectin and this depression was recovered by prior alpha
      galactosidase digestion. In addition, the present method was successfully applied
      for the estimation of the content of B antigens neo-expressed in thyroid
      papillary carcinomas, showing that the content of B antigen had a similar level
      to that of red blood cells and vascular endothelial cells.

PMID- 9151131
TI  - Objective differential classification of thyroid lesions by nuclear quantitative
      assessment.
AB  - Quantitative nuclear parameters estimated by morphometric and stereological
      methods in combination with discriminant analysis were used in order to evaluate
      the diagnostic efficiency of thyroid lesions. This study includes 55 patients
      with thyroid pathology. Samples of follicular adenomas, follicular carcinomas,
      and papillary carcinomas were examined by image analysis to obtain size and form
      nuclear parameters. Stepwise discriminant analyses were performed. There was an
      increase in nuclear size from follicular adenomas to follicular carcinomas, and a
      greater increase from follicular carcinomas to papillary carcinomas. The increase
      was more significant when the three-dimensional estimates of the volume-weighted
      mean nuclear volume were assessed. No significant differences between follicular
      adenomas and follicular carcinomas were found with respect to the nuclear form
      factors, however, a significant increase in nuclear elongation and irregularity
      was registered between follicular and papillary tumors (p < 0.01). The overall
      accuracy rate of discrimination was 75% when the three lesions were included in
      the analysis, with an efficiency of 85% for papillary carcinoma samples. These
      percentages increased when two lesion discrimination was performed. The worst
      discrimination (69% of efficiency) was found between follicular adenomas and
      follicular carcinomas.

PMID- 9151132
TI  - Ultrastructure of atheromatous lesions experimentally induced in Syrian hamsters
      of the APA strain.
AB  - In order to examine whether diabetes enhances, primary aortic lesions up to
      atherosclerotic ones, mild primary lesions were induced in aorta of APA hamsters
      by an administration of vitamin D2 (VD) and/or stop-and-reflow (SR)-operation, a
      modification of renal artery clamping. At 2 months after the treatment with the
      combination of VD-administration and SR-operation, atheromatous lesions,
      characterized by an appearance of many foam cells in the intima, were observed in
      the abdominal aorta, the site of SR-operation, in streptozotocin (SZ)-induced
      diabetic APA hamsters. Foam cells in the atheromatous lesions were originated
      from smooth muscle cells and monocyte/ macrophages. On the other hand, neither VD
      administration alone nor SR-operation alone developed atheromatous lesions in SZ
      induced diabetic APA hamsters. In conclusion, we succeeded in a rapid induction
      of atherosclerotic lesions in abdominal aorta of SZ-induced diabetic APA hamsters
      by the combination of VD-administration and SR-operation.

PMID- 9151133
TI  - 5-Azacytidine (5Az) induces apoptosis in PC12 cells: a model for 5Az-induced
      apoptosis in developing neuronal cells.
AB  - Our previous in vivo and in vitro studies showed that 5-azacytidine (5Az), a
      cytidine analog, induced apoptosis in developing neuronal cells in mice. To
      develop a system in which the precise molecular mechanism of 5Az-induced
      apoptosis in developing neuronal cells could be elucidated, we carried out the
      present study with PC12 cells. These cells are derived from a rat
      pheochromocytoma and extrude neurites in response to nerve growth factor (NGF).
      Light microscopy showed dose-dependent pyknotic and karyorrhectic changes in
      undifferentiated PC12 cells. Although they were less sensitive to 5Az, NGF
      treated differentiated cells showed the same changes. Analysis by the TUNEL
      method (an in situ method for the detection of apoptosis) showed positive signals
      in the pyknotic and fragmented nuclei of these cells. Transmission electron
      microscopy revealed margination, segmentation, and condensation of nuclear
      chromatin, cell body shrinkage, and cytoplasmic vacuolization. Scanning electron
      microscopy demonstrated bleb formation on the cell surface. These
      pathomorphological changes are typical of apoptosis. 5Az seemed to affect cells
      that were in the proliferative stage; when the cells were terminally
      differentiated, their sensitivity to 5Az appeared to decline. PC12 cells could be
      used as a pathomorphological and biochemical model for studies of 5Az-induced
      neuronal cell apoptosis at the molecular and genetic level.

PMID- 9151134
TI  - Field emission SEM, conventional TEM and HVTEM study of submandibular gland in
      prenatal and postnatal aging mouse.
AB  - The development of acinar and ductal cells of the mouse submandibular gland was
      studied using field emission SEM, conventional TEM and HVTEM methods. The
      specimens, at 15 and 18 days of gestation and 1, 3, 7, 14, 21, 30, 90 and 180
      postnatal days were fixed in 2.5% glutaraldehyde solution in 0.1 M sodium
      phosphate buffer (pH 7.3). At 15 and 18 days of gestation, the structure of mouse
      submandibular gland contains acinar and ductal cells in proliferation. The
      cytoplasmic organelles such as mitochondria, granular endoplasmic reticulum and
      Golgi apparatuses are scattered in the cytoplasm. At 18 prenatal days only
      several acinar cells present immature secretory granules in the apical portion.
      In this stage the acinar and ductal cells are enveloped by bundles of fine
      collagen fibrils disposed in several directions. There are also numerous
      capillaries located closely to the acinar cell membranes. In the aging stages of
      1, 3, 7, 14, 21, and 30 postnatal days, the histo-differentiation of acinar,
      intercalated and ductal cell components are observed. At newborn day one the
      cytoplasmic organelles start to place themselves around the nucleus. Several
      immature secretory granules are observed at day one, however, they increase in
      the aging days. At postnatal day 30, the cytoplasms of acinar and ductal cells
      are filled with a large number of secretory granules of different sizes. The
      stacks of granular endoplasmic reticulum and Golgi apparatus and some vesicles
      and free ribosomes are noted. The intercellular membranes are attached by
      desmosomes and cytoplasmic interdigitations. The luminal surface shows several
      small projections of microvilli. An electron-dense line of basement membranes
      followed by fine collagen fibrils are recognized. Delicate capillaries are found
      in the outer surface of acinar cells. At postnatal day 90 and 180 the acinar,
      intercalated and striated ductal cells reveal numerous secretory granules in the
      apical portion. The acinar cells showed basal nuclei and the parallel arrangement
      of granular endoplasmic reticulum. The mitochondria are located at the base of
      ductal cells showing a typical pattern of cristae. In these stages the
      intercellular digitations of cytoplasmic protrusions and desmosomes are also
      noted. The cytoplasm of myoepithelial cells are seen along the cell membranes.
      The spongy-like structures constituting the basement membrane are followed by
      bundles of fine collagen fibers.

PMID- 9151135
TI  - Growth factors and remyelination in the CNS.
AB  - It is now well established that there is an inherent capacity within the central
      nervous system (CNS) to remyelinate areas of white matter that have undergone
      demyelination. However this repair process is not universally consistent or
      sustained, and persistent demyelination occurs in a number of situations, most
      notably in the chronic multiple sclerosis (MS) plaque. Thus there is a need to
      investigate ways in which myelin deficits within the CNS may be restored. One
      approach to this problem is to investigate ways in which the inherent
      remyelinating capacity of the CNS may be stimulated to remyelinate areas of long
      term demyelination. The expression of growth factors, which are known to be
      involved in developmental myelinogenesis, in areas of demyelination strongly
      suggests that they are involved in spontaneous remyelination. Therefore delivery
      of exogenous growth factors into areas of persistent demyelination is a potential
      therapeutic strategy for stimulating remyelination. This review will discuss the
      evidence that growth factors may have a role in promoting CNS remyelination by
      enhancing the survival and stimulating the proliferation and recruitment of
      remyelinating oligodendrocytes.

PMID- 9151136
TI  - Adhesion molecules as targets for cancer therapy.
AB  - Adhesion molecules mediate cell-cell and cell-matrix interactions and are
      essential for numerous physiological and pathological processes. Recent evidence
      from many laboratories suggests that adhesion molecules play an important role in
      tumor progression and may promote tumor growth and organ-specific metastasis.
      Certain adhesion molecules may also function as tumor suppressors. In this
      review, we describe current concepts concerning the role of the adhesion
      molecules in the pathogenesis of cancer and the development of therapeutic
      approaches which make use of this information. Hence, by preventing tumor cells
      from interacting with each other or with their microenvironment, tumor growth and
      metastasis can be suppressed. The feasibility of using anti-adhesion strategies
      to treat cancer has been demonstrated in many animal models. Thus, monoclonal
      antibodies (MAbs) against adhesion molecules, synthetic peptidic and nonpeptidic
      analogues of the recognition sequences on their receptors, soluble adhesion
      molecules and antisense oligonucleotides can inhibit tumor growth and gene
      therapy can restore the functions of altered tumor-suppressive adhesion
      molecules.

PMID- 9151137
TI  - The microanatomy of calcium stores in human neutrophils: relationship of
      structure to function.
AB  - As changes in cytosolic free Ca2+ play key roles in coupling responses in
      neutrophils, it is important to locate and identify Ca2+ storage sites within
      these cells. Here, recent data is presented which highlights the functional link
      between microanatomical structure and cell signalling function. Fluorescent
      optical probes for cytosolic free Ca2+ have been used, together with organelle
      specific markers. We present evidence from conventional fluorescence microscopy,
      together with ratiometric and confocal laser scanning fluorescence microscopy,
      which pin-points two cellular locations for Ca2+ within the neutrophil; one
      within the nuclear lobes, and the other towards the cell periphery. Knowledge of
      these two locations provides a clear insight into how signalling in this cell
      type is regulated and provides a framework for explaining how specific stimuli
      act to produce specific responses.

PMID- 9151138
TI  - Gastric mucosal injury and repair: effect of aging.
AB  - Although the gastric mucosa of healthy adult animals possesses the inherent
      capacity to promptly repair (often within 24 h) after a minor to moderate injury,
      aging appears to diminish its reparative capacity. At least two different repair
      mechanisms are thought to participate in full repair of the damaged gastric
      mucosa: the initial rapid process of mucosal restitution begins by migration of
      viable epithelial cells from gastric pits and glands; the subsequent slower
      process is replacement of lost cells by cell division. Intracellular events that
      regulate these processes are poorly understood, nor do we know how they may be
      affected by aging. However, evidence is accumulating which suggests that a number
      of gastrointestinal hormones/growth factors, most notably EGF and TGF-alpha may
      play a critical role in regulating gastric mucosal reparative processes. Since
      EGF and TGF-alpha exert their physiological actions by activating the intrinsic
      tyrosine kinase (Tyr-k) activity of their common receptor, the EGF-R, studies
      have been performed to assess the role of EGF-R Tyr-k in regulating mucosal
      reparative processes during aging. Recent data suggest that the age-related
      decline in mucosal repair after acute injury could in part be due to decreased
      activation of EGF-R Tyr-k. In addition, polyamines and prostaglandins are also
      thought to be involved in gastric mucosal reparative processes. Although the
      involvement of polyamines in gastric mucosal reparative processes during aging
      has not yet been studied, decreased mucosal prostaglandin levels in the aged are
      thought to be a causative factor for the increased susceptibility of the mucosa
      to injury. These and other relevant matters are discussed in the current review.

PMID- 9151139
TI  - Neuropeptides in the seminal vesicles: locations, binding sites and functional
      implications.
AB  - The importance of neuronal factors in the normal physiology of the seminal
      vesicles has been traditionally underestimated when compared to the trophic role
      of androgens. Immunohistochemical, autoradiographical and pharmacological
      experiments have, however, raised the possibility that neuropeptides, such as
      vasoactive intestinal polypeptide (VIP), neuropeptide tyrosine (NPY) and
      calcitonin gene-related peptide (CGRP), are necessary for full seminal vesicle
      function and development. These neuropeptides may be involved in the regulation
      of secretion, smooth muscle tone and blood flow. Furthermore, neuropeptides may
      have functional interactions with androgens affecting, probably, androgen
      receptor-dependent gene expression in these glands. It is now timely to focus
      attention on the biological relevance of neuropeptides in the seminal vesicles.

PMID- 9151140
TI  - Distribution and pathophysiologic role of molybdenum-containing enzymes.
AB  - The importance of molybdenum-containing enzymes in the pathophysiology of a
      number of clinical disorders necessitates a comprehensive understanding of their
      histological localization and expression. The objectives of this review are to
      cover such enzymes so far reported and their enzyme- and immunohistochemical
      localization in various tissues and species, and to discuss their possible
      pathophysiological effects. The molybdenum cofactor is essential for the activity
      of the three molybdenum-containing enzymes, sulfite oxidase, xanthine oxidase and
      aldehyde oxidase. Sulfite oxidase serves as the terminal enzyme in the pathway of
      the oxidative degradation of sulfur amino acids, and is also involved in
      preventing the toxic effects of sulfur dioxide. Biochemical study has revealed a
      high activity of sulfite oxidase mainly in the liver, heart and kidney with
      lesser activity observed in other tissues. Subcellular observations have shown
      that this enzyme is present in the mitochondrial intermembraneous spaces.
      Xanthine oxidase is the final enzyme in the conversion of hypoxanthine to
      xanthine, and subsequently, to uric acid. Unlike sulfite and aldehyde oxidases,
      xanthine oxidase can be converted to xanthine dehydrogenase, and vice versa.
      Xanthine oxidase has been widely investigated for its role in post-ischemic
      reperfusion tissue injury. Enzyme- and immunohistochemical studies of its
      localization in various animal species and tissues have shown its ubiquitous
      distribution in the liver, small and large intestine, lung and kidney, and other
      tissues. Aldehyde oxidase shares a similar substrate specificity with xanthine
      oxidase. Although the tissue localization of this enzyme has not been studied as
      thoroughly as that of xanthine oxidase, aldehyde oxidase is reportedly found in
      the digestive gland of terrestrial gastropods, the antennae of certain moths as
      well as the mammalian liver. Recently, the ubiquitous distribution of aldehyde
      oxidase has been demonstrated in rat tissues. The aldehyde oxidase activity of
      herbivores exceeds that of carnivores, suggesting a possible role of this enzyme
      as a protection against the effects of toxic plants. The relationship between the
      tissue localization of these enzymes and their pathophysiological roles is
      reviewed.

PMID- 9151141
TI  - Antioxidant enzyme levels in cancer.
AB  - Normal cells are protected by antioxidant enzymes from the toxic effects of high
      concentrations of reactive oxygen species generated during cellular metabolism.
      Even though cancer cells generate reactive oxygen species, it has been
      demonstrated biochemically that antioxidant enzyme levels are low in most animal
      and human cancers. However, a few cancer types have been found to have elevated
      levels of antioxidant enzymes, particularly manganese superoxide dismutase.
      Morphologic studies of animal and human cancer have confirmed that although the
      majority of tumor cell types from several organ systems have low antioxidant
      enzymes, adenocarcinomas may have elevated manganese superoxide dismutase and
      catalase levels. However, all cancers examined to date have some imbalance in
      antioxidant enzyme levels compared with the cell of origin. Antioxidant enzyme
      importance in cancer genesis has been difficult to evaluate in early cancerous
      lesions using biochemical techniques because such lesions are small and therefore
      below the level of detection. Using immunohistochemical techniques, early lesions
      of human and animal cancers were demonstrated to have low antioxidant enzymes,
      thus suggesting a role for these enzymes both in the genesis of cancer and the
      malignant phenotype. All but one human cancer cell type (the granular cell
      variant of human renal adenocarcinoma) examined showed both low catalase and
      glutathione peroxidase levels, suggesting that most cancer cell types cannot
      detoxify hydrogen peroxide. Our results to date are used to propose new cancer
      therapies based on modulation of cellular redox state.

PMID- 9151142
TI  - Hepatocyte growth factor/scatter factor, a cytokine playing multiple and converse
      roles.
AB  - Hepatocyte growth factor (HGF), otherwise known as scatter factor (SF), is a
      recently identified cytokine which exerts a wide spectrum of biological functions
      on a variety of cell types. Its receptor is encoded by the c-met proto-oncogene.
      HGF/SF has been implicated in the regulation of mitogenesis, motogenesis, and
      morphogenesis. Over the past few years, the structure, function and signal
      transduction pathways of HGF/SF and its receptor have become clearer. The
      cytokine is now known to play important roles in the regulation of both normal
      physiological processes as well as pathological ones. This review summarises
      recent progress involving HGF/SF and its receptor and discusses their role in
      cell biology, organ regeneration, cancer and other processes. Hepatocyte growth
      factor (HGF) is a pleiotropic growth factor originally identified as a potent
      mitogen agent for rat hepatocytes. Subsequent studies have shown that it is
      mitogenic for a wide range of epithelial cells and not limited to hepatocytes.
      Its behaviour as a motogenic stimulator promoted its independent discovery and
      naming of scatter factor (SF). Analysis of cDNA and amino acid sequences have
      revealed that the two molecules are the same. A number of cytokine agents are
      known to stimulate cellular motility, however, it is the function of HGF/SF as a
      potent motogenic, mitogenic and morpho-regulatory agent on the diverse variety of
      cell types that makes the discovery of HGF/SF factor one of the most interesting
      stories in terms of identification of novel cytokines.

PMID- 9151143
TI  - Collagen types VIII and X, two non-fibrillar, short-chain collagens. Structure
      homologies, functions and involvement in pathology.
AB  - Collagens can be divided into two groups, i.e., fibrillar and non-fibrillar
      collagens. Short-chain collagens, a subgroup of non-fibrillar collagens,
      comprises collagen type VIII and type X. These two collagen types show several
      similarities in structure and possibly also in function. Type VIII collagen
      appears to be secreted by rapidly proliferating cells. It can be found in
      basement membranes and may serve as a molecular bridge between different types of
      matrix molecules. In different tissues this collagen type may serve different
      functions. Stabilization of membranes, angiogenesis, and interactions with other
      extracellular matrix molecules. Since collagen type X is produced by hypertrophic
      chondrocytes, this collagen type can only be found in matrix of the hypertrophic
      zone of the epiphyseal growth plate cartilage. Collagen type X is probably
      involved in the process of mineralization, endochondral ossification, and is also
      proposed to play a role in angiogenesis. Collagen types VII and X may be involved
      in matrix and bone disorders. Their structure, function, and involvement in
      pathology are discussed in this review.

PMID- 9151144
TI  - Immunocytochemical correlates of an extrapituitary adrenocortical regulation in
      man.
AB  - Investigations reviewed in this article provide cytochemical and functional
      support for a significant involvement of extrapituitary factors in human
      adrenocortical functions. Among these factors neural messengers may play a
      crucial role in the adrenocortical regulation, arising from specifically coded
      postganglionic neurons with both, extrinsic and intrinsic locations, as well as
      from chemically characteristic afferent neurons. The close association of
      varicose transmitter segments with steroid hormone synthesizing cells and their
      occurrence at arteries and sinusoid capillaries are indicative for both direct
      and indirect regulatory mechanisms on cortical functions. The immunohistochemical
      presence of neuropeptides and cytokines in endocrine and/or immune cells of the
      human adrenal medulla and cortex as well as specific binding sites on
      steroidogenic cells indicate the modulatory implication of additional short
      paracrine- and ultrashort-autocrine-feedback loops on cortical cell proliferation
      and steroid metabolism. The summarized data suggest that basal endocrine
      influence of the hypothalamo-pituitary axis on adrenocortical growth and
      functions in man is controlled by the nervous system that also regulates local
      fine-tuning of human cortical activity.

PMID- 9151145
TI  - Molecular clues to pathogenesis in prion diseases.
AB  - The infectious agent of the transmissible spongiform encephalopathies (TSE)
      resembles a virus in that it propagates in vivo and has distinct strains.
      However, compelling evidence strongly suggests that a posttranslational
      structural alteration in a glycoprotein PrPC (the normal, cellular isoform of the
      so-called prion protein) is responsible for pathogenesis of these diseases.
      According to this hypothesis-now close to being generally accepted-iatrogen,
      sporadic and familial forms of TSE would have the same molecular mechanism: the
      conversion of PrPC into a protease-resistant isoform PrPSc kinetically behaves as
      an autocatalytic process which, combined with the high turnover rate of the
      normal isoform, may endow the system with bistability properties and subsequent
      threshold behavior between normal and pathogenic steady-states. Normal prion
      protein seems to be necessary for long-term survival of Purkinje neurons,
      regulation of circadian rhythms and, more controversially, for normal synaptic
      function. At least part of the pathology might be due to the unavailability of
      normal isoform rather than to the accumulation of PrPSc. NMR structure of the
      normal mouse prion protein reveals a short, unexpected beta-sheet which might be
      a nucleation site for the conformational transition between PrPC and PrPSc. Prion
      diseases may challenge the edged distinction that we use to make between
      informational (DNA) and functional (proteins) macromolecules. Pathogenic
      mechanism of prions might also be involved in other proteins to achieve and pass
      on their conformation. Hence, structural inheritance at the molecular level might
      be the missing link for the understanding of the structural inheritance processes
      featured at the cellular level. Moreover, evolutionary paradigm postulating a
      primitive RNA world is weakened by the mechanism of prion diseases.

PMID- 9151146
TI  - Making long-term peritoneal dialysis possible.

PMID- 9151147
TI  - Do potassium deficient diets and K+ removal by dialysis contribute to the
      cardiovascular morbidity and mortality of patients with end stage renal disease?

PMID- 9151149
TI  - Permeability and adsorption capacity of dialysis membranes to lipid A.
AB  - Hemodialysis membranes were tested in vitro for possible penetration by low
      molecular weight endotoxins containing lipid A. Using lipid A from Escherichia
      coli as a model substance for this kind of pyrogen, different dialyzers (F4, E3.
      Acepal 1300, Altraflux, F 40, Polyflux 110, Filtral 12, F 60) were challenged by
      tangential filtration in aqueous medium. All membranes exhibited impermability to
      lipid A (as well as to LPS from Pseudomonas aeruginosa), which was proved by
      additional experiments using culture filtrates of Pseudomonas aeruginosa in
      bicarbonate dialysis fluid, as well as by employing miniaturized dialyzers with
      synthetic lipid A as a contaminant. Furthermore, the highest adsorption
      capacities were found for polysulfone and polyamide membranes.

PMID- 9151148
TI  - Beta 2-microglobulin removal by synthetic dialysis membranes. Mechanisms and
      kinetics of the molecule.
AB  - Beta 2-microglobulin (beta 2-m) accumulation represents a possible complication
      of long term dialysis. It is therefore important to evaluate the capacity of
      removal of this molecule from the patient by different dialysis membranes. The
      present study is aimed at evaluating the mechanisms involved in beta 2-m removal
      by three different synthetic membranes: a) highly asymmetric hydrophobic
      polysulfone (Biosulfane, NMC), b) moderately asymmetric and hydrophobic
      polysulfone (PS600, Fresenius), c) Polyacylonitrile (AN69HF, Hospal). The
      adsorption capacity and sieving coefficients of the three membranes for native
      and labeled beta 2-m were studied in vitro utilizing human blood. The amount
      adsorbed by the membrane was measured by the elution of the molecule obtained
      with a detergent solution. Clearances, total removal and membrane adsorption were
      studied in six patients treated in a randomized sequence with the three
      membranes. For this purpose, plasma and dialysate measurements as well as total
      collection of spent dialysate and beta 2-m elution from the used dialyzers were
      carried out. Ex novo generation of beta 2-m did not take place during in vitro
      circulation. The molecule was removed by the studied membranes both by filtration
      and adsorption. The Biosulfane membrane removed beta 2-m mostly by adsorption
      while the PS600 membrane removed beta 2-m almost entirely by filtration.
      Intermediate behaviour was shown by AN69 membrane. Similar quantities of beta 2-m
      were removed from the patients with the three membranes. Total removal could only
      be precisely measured by adding the quantity of beta 2-m eluted from the membrane
      to the amount recovered in the spent dialysate. Out of total removal, adsorption
      was more than 90% with Biosulfane, while only 5% with the PS600. These findings
      contribute to the understanding of the discrepancy found between the clearance
      measured from the plasma side and that measured from the dialysate side. In
      conclusion, clearance and sieving measurements for beta 2-m cannot be correctly
      performed unless the capacity of adsorption of the membrane is taken into
      account.

PMID- 9151150
TI  - Clinical evaluation of AK 100 ULTRA for predilution HF with on-line prepared
      bicarbonate substitution fluid. Comparison with HD and acetate postdilution HF.
AB  - Convective transport across dialysis membranes has been known for a long time to
      be a good alternative to diffusion. Predilution hemofiltration (HF) offers a
      better clearance of small molecules and overcomes the blood viscosity problems
      related to conventional postdilution HF treatment. Three patients have performed
      a total of 293 predilution HF treatments with AK 100 ULTRA. The bicarbonate
      substitution fluid has been prepared on-line by the machine. The treatments have
      been well tolerated and no adverse patients reactions related to the quality of
      the substitution fluid or the predilution HF treatment have been observed. There
      is a drop in creatinine for all patients indicating an improved creatinine
      clearance. Bicarbonate predilution HF has been shown to be a safe and efficient
      treatment modality, it offers the possibility to improve the cardiovascular
      stability of patients having problems with other treatment modalities an it
      offers an improved intertreatment well-being for the patients.

PMID- 9151151
TI  - Comparison between urea removal in hemodialysis and continuous ambulatory
      peritoneal dialysis using a mathematical kinetic model.
AB  - Urea removal by continuous ambulatory peritoneal dialysis (CAPD) was compared
      with that by hemodialysis (HD) using a mathematical kinetic model. The time
      averaged urea-nitrogen concentration (TAC) in the blood of a patient on
      maintenance HD was calculated by the model. Clearance with HD giving a TAC value
      equal to the constant urea-nitrogen concentration in the blood of a patient on
      CAPD was obtained, leading to the relation of equivalent clearances between HD
      and CAPD on the assumption that the urea-generation rate of the patient on CAPD
      was equal to that of the patient on HD.

PMID- 9151152
TI  - Coagulation activation in extracorporeal hemodialysis.
AB  - The authors evaluated the behavior of protein C activity, factor X and factor VII
      coagulant activity and serum lipoprotein(a) before and after dialytic treatment
      in patients on maintenance hemodialysis. They observed depressed protein C
      activity that significantly (p < 0.005) increased and became normal immediately
      after hemodialysis while factor X and factor VII increased (p < 0.01; p < 0.05)
      despite heparinization together with amount of serum lipoprotein(a). In vitro
      incubation (30' at 37 degrees C) of uremic and healthy blood showed a decrease in
      serum lipoprotein(a) concentration. After heparin addition (final concentration
      0.5 U/ml) lipoprotein(a) increased in the uremic blood only. The clinical and
      physiopathological implications of these results are discussed.

PMID- 9151153
TI  - The use of a heparin removal device: a valid alternative to protamine.
AB  - PURPOSE: Experiments were carried out to test the efficacy and safety of the
      heparin removal device, a plasmapheresis filter that binds and eliminates
      heparin, in the context of extracorporeal circulation. PROCEDURES AND FINDINGS:
      Six dogs were put on cardiopulmonary bypass after heparinization. Upon weaning,
      additional heparin was administered to obtain an activated clotting time above
      900s. The animals were connected to the heparin removal device and with flows of
      500 ml/min, activated clotting time, activated partial thromboplastin time and
      plasma heparin concentrations were normalised to baseline after 30 min.
      Hemodynamic parameters remained unaffected. A slight decrease in red and white
      blood cell count and in platelets was observed which however recovered
      spontaneously two hours after the filter procedure. No damage to blood components
      could be observed. CONCLUSIONS: The use of a heparin removal device is as
      efficient as systemic administration of protamine to reverse the effects of
      heparinization. It may prevent the adverse reactions linked to protamine
      administration and therefore be indicated in certain subgroups of patients
      undergoing cardiopulmonary bypass.

PMID- 9151154
TI  - Cardiopulmonary by-pass in a patient with acquired C1 inhibitor deficiency.
AB  - C1 inhibitor (C1-INH) regulates, complement, contact system, coagulation and
      fibrinolysis. Bleeding complications during cardiopulmonary bypass (CPB) have
      been described in a deficient patient. We report a 72 year old man affected with
      acquired C1-INH deficiency who successfully underwent CPB.

PMID- 9151156
TI  - Long-term therapy for uremic bleeding: effects of conjugate estrogens on the
      expression of platelet surface receptors for von Willebrand factor and fibrinogen
      (GPIb and GPIIb/IIIa glycoproteins)

PMID- 9151157
TI  - Stress corrosion in prosthetic heart valves.

PMID- 9151155
TI  - Changes in bradykinin and prostaglandins plasma levels during dextran-sulfate low
      density-lipoprotein apheresis.
AB  - The negative charges of dextran-sulfate (DS) used for low-density-lipoprotein
      (LDL) apheresis initiate the intrinsic coagulation pathway in which plasma
      kallikrein acts on the high-molecular-weight kininogen to produce large amounts
      of bradykinin. This study was undertaken to assess whether bradykinin generated
      during DS LDL apheresis has any physiologic effects in vivo. The plasma levels of
      bradykinin, prostaglandins and cyclic guanosine monophosphate (cGMP) were
      compared. when either of two anticoagulants, heparin or nafamostat mesilate (NM),
      was used during DS LDL apheresis. Although anticoagulative action by NM depends
      on the inhibition of thrombin activity this substance also inhibits the activity
      of plasma kallikrein. During apheresis using heparin, the plasma levels of
      prostaglandin E2 (PGE2) increased significantly (5.6 +/- 1.2 (mean +/- SE, n = 4)
      pg/ml before apheresis and 33.4 +/- 13.2 after apheresis, p < 0.05) in
      association with an increase in bradykinin levels (17.9 +/- 2.6 pg/ml before
      apheresis and 470 +/- 135 after apheresis, p < 0.01). Interestingly, these
      changes were suppressed during apheresis using NM. There were no appreciable
      changes in cGMP during DS LDL apheresis with either of the anticoagulants. This
      finding suggests that bradykinin generated during apheresis has some
      pathophysiological effects via activation of the prostaglandin system. Our
      results support the view that in patients taking angiotensin-converting-enzyme
      inhibitors, the anaphylactoid reaction occurring during apheresis may be caused
      by an excessive rise in the bradykinin levels.

PMID- 9151158
TI  - Cell response to hyperbaric oxygen treatment.
AB  - Wound healing involves matrix deposition, angiogenesis, and new tissue growth.
      Cellular activity during healing is related to tissue oxygen levels. Since wound
      healing requires oxygen, the purpose of this study was to investigate the effects
      of hyperbaric oxygen (HBO) on cells involved in wound healing. Cultured
      endothelial cells and fibroblasts were exposed to HBO. The effect of varied
      partial pressure, oxygen saturation, and duration and frequency of exposure to
      HBO on cell proliferation was determined by 3H-labeled thymidine incorporation.
      HBO causes an increase in the partial pressure of oxygen in the medium of
      cultured cells, leading to increased endothelial cell and fibroblast
      proliferation. Increased endothelial cell proliferation occurred after 15 min of
      HBO. Fibroblasts required 120 min of HBO to produce a response. A second exposure
      to HBO on the same day produced no additional increase in cell proliferation. A
      120-min HBO exposure stimulated fibroblast proliferation for 72 h after the
      exposure. An increase in pressure from 2.4 to 4.0 atmospheres absolute did not
      enhance the proliferative response. These studies begin to elucidate the effects
      of HBO on cells involved in wound healing and establish a scientific foundation
      upon which to develop more efficacious and cost-effective HBO therapeutic
      protocols.

PMID- 9151159
TI  - The influence of orthognathic surgery on occlusal force in patients with vertical
      facial deformities.
AB  - This study utilized bite-force measurements to determine the effect of various
      orthognathic surgery procedures on occlusal force generation in 42 patients with
      vertical facial deformities. The results showed that orthognathic surgery
      produced marked alterations in occlusal force levels which continued to occur up
      to a year after surgery. Measurements indicated that advancement of the mandible
      may result in weaker force levels, while bimaxillary surgery for the treatment of
      a "long face" brings the previously weaker bite force to a more "normal" level.

PMID- 9151160
TI  - Treatment of recurrent mandibular dislocation, Part I: Leclerc blocking
      procedure.
AB  - Nine patients with recurrent mandibular dislocation, who underwent the blocking
      procedure of Leclerc and Girard, as modified by Gosserez and Dautrey, are
      presented. The follow-up period range from 2.5 to 5 years. An axiographic study
      revealed significant postoperative limitation of translation of the condyle when
      opening, while maximal mouth opening as measured between the incisors, as well as
      translation of the condyle in protrusion and mediotrusion, showed no significant
      limitation. Long-term evaluation showed a high incidence of clicking and pain,
      not evident prior to surgery. The causes for recurrence in three cases were
      analysed.

PMID- 9151161
TI  - Treatment of recurrent mandibular dislocation, Part II: Eminectomy.
AB  - Fourteen patients underwent eminectomy for recurrent mandibular dislocation. The
      clinical follow-up period ranged from 7 months to 5 years. The function of the
      temporomandibular joint before and after eminectomy was analysed clinically and
      by computer-aided axiography. There was no significant decrease in the condylar
      path angle postoperatively, though the articular eminence had been removed up to
      its most medial portion. Translatory border movements showed significant
      limitation six months after surgery and normal range of motion in the first and
      second year after the operation. Postoperative hypermobility of the condyle was
      not observed.

PMID- 9151162
TI  - A method of harvesting corticocancellous bone chips for reconstructive
      maxillofacial surgery.
AB  - A method is described to harvest bone chips for maxillofacial surgery with large
      burs and a special collecting net connected to a suction device. Three nets and
      four burs were tested in vitro on a pig mandible to determine the optimal
      combination. All burs produced bone chips of rather similar sizes. The midsized
      net (hole diameter 0.5 mm) collected most bone chips during a 1-min drilling.

PMID- 9151163
TI  - Mandibular bone graft in the anterior maxilla for single-tooth implants.
      Presentation of surgical method.
AB  - Nine patients with 10 implants were included in the study. A bone graft from the
      symphyseal region of the mandible was used to augment the ridge 4 months before
      implant insertion. All implant sites showed a sufficient amount of bone at the
      time of implant insertion. One implant was not integrated at the time of abutment
      connection. Bone resorption after augmentation was assessed by measurements of
      the width of the alveolar ridge at four different levels. The measurements were
      performed before and after the bone-grafting procedure, at implant insertion and
      at abutment connection. The bone resorption in the buccal/palatal direction was
      60% when measured from the time of bone grafting to abutment connection. The bone
      resorption was already obvious after 4 months (25%). The results indicate that
      the described bone grafting technique is applicable in patients with a narrow
      alveolar ridge, even though the resorption of the graft was extensive.

PMID- 9151164
TI  - Foreign body in the maxillary antrum. A case report.

PMID- 9151165
TI  - Detection of unknown primary head and neck tumors by positron emission
      tomography.
AB  - The purpose of this study was to investigate the potential of using positron
      emission tomography (PET) with 18F-labeled fluoro-2-deoxy-D-glucose (FDG) to
      detect unknown primary tumors of cervical metastases. Thirteen patients with
      various histologic types of cervical metastases of unknown primary origin were
      studied. Patients received 185-370 MBq FDG intravenously and were scanned from 30
      min after injection onward. Whole-body scans were made with a Siemens ECAT 951/31
      PET camera. PET identified the primary tumor in four patients: plasmocytoma,
      squamous cell carcinoma of the oropharynx, squamous cell carcinoma of the larynx,
      and bronchial carcinoma, respectively. All known metastatic tumor sites were
      visualized. PET did not identify a primary tumor in one patient in whom a
      squamous cell carcinoma at the base of the tongue was found in a later phase. In
      the remaining eight patients, a primary lesion was never found. The follow up
      ranged from 18 to 30 months. A previously unknown primary tumor can be identified
      with FDG-PET in approximately 30% of patients with cervical metastases. PET can
      reveal useful information that results in more appropriate treatment, and it can
      be of value in guiding endoscopic biopsies for histologic diagnosis.

PMID- 9151166
TI  - Selection of adenoid cystic carcinoma cell clone highly metastatic to the lung:
      an experimental study.
AB  - Lung metastasis is very common in patients with adenoid cystic carcinoma (ACC).
      The purpose of the present study is to establish a model for an experimental
      study of ACC metastatic mechanisms and antimetastatic procedures. After five
      repeated selection in vivo, combined with an in vitro cloning technique and
      analysis of platelet aggregation activity, a clone (Acc-M) highly metastatic to
      the lung was selected from an ACC cell line (Acc-2). The metastatic rate was 96%
      vs 18% for Acc-M and the Acc-2 cell line. The metastatic rate and the weight of
      the lung with metastases correlated positively with platelet aggregation
      activity. The present study might be important for research into mechanisms of
      ACC metastases.

PMID- 9151167
TI  - Squamous cell carcinoma of the lower lip in renal-transplant recipients. Report
      of six cases.
AB  - The incidence of squamous cell carcinoma of the lower lip in immunosuppressed
      renal-transplant recipients is considerably higher than in the normal population.
      In addition to immunosuppressive treatment, the most important risk factors for
      the development of lip cancer in these patients are exposure to sunlight and
      smoking habits. Regular surveillance of renal-transplant recipients and early
      biopsy of premalignant lesions of the lip allow early detection of lip cancer.
      Patients should also be advised to avoid unprotected exposure to sunlight, to use
      appropriate sunscreens and to stop smoking. Six cases of squamous cell carcinoma
      of the lower lip in renal-transplant recipients are described.

PMID- 9151169
TI  - Chondrolipoma of the tongue. A case report.
AB  - Chondrolipoma is a rare benign oral tumour. We present a case in a 68-year-old
      diabetic woman.

PMID- 9151168
TI  - Gustatory rhinorrhea after maxillectomy. Two case reports and considerations on
      etiology and pathophysiology.
AB  - Gustatory rhinorrhea consists of free discharge of thin mucus from the nose
      during ingestion or after other gustatory stimulus. At maxillectomy, the nerve
      fibers going both to the salivary glands of the palate and to the secretory
      glands of the nasal mucosa may be damaged. A misdirection between the
      regenerating fibers of these two groups produces gustatory rhinorrhea.

PMID- 9151170
TI  - Metaphyseal fibrous defect (nonossifying fibroma) in the mandible. A case report.
AB  - A 7-year-old boy presented in whom a metaphyseal fibrous defect was diagnosed.
      The lesion was enucleated under local anesthesia. The postoperative course was
      uneventful and there have been no signs of recurrence as of 14 months after
      operation. Although rare, metaphyseal fibrous defect should be included in the
      differential diagnosis of tumors arising in the jaws.

PMID- 9151171
TI  - Characterization and management of deep neck infections.
AB  - A retrospective review was conducted of 91 patients with deep neck infections to
      determine the pattern of clinical disease and formulate a management plan. The
      spaces involved, as determined by clinical, radiologic, and operative findings,
      were the peritonsillar space (72 patients), parapharyngeal space (eight patients)
      submandibular space (seven patients), retropharyngeal space (one patient)
      superficial space (one patient), anterior visceral space (one patient), and
      visceral vascular space (one patient). Of the 19 patients who did not have a
      peritonsillar space infection the origin of the infection was found in eight;
      four of these were odontogenic. Thirty-eight patients required surgical drainage
      of the abscess. Five patients underwent tracheotomy due to increasing dyspnea.
      One patient with diabetes mellitus and a past history of myocardial infarction
      died of unknown cause. All other patients had an uneventful recovery without
      major complications. The combination of early radiologic diagnosis, effective
      antimicrobial therapy, and intensive surgical management contributed to the good
      prognosis.

PMID- 9151172
TI  - Flexible (Polyactive) versus rigid (hydroxyapatite) dental implants.
AB  - In a beagle dog study, the peri-implant bone changes around flexible (Polyactive)
      and rigid hydroxyapatite (HA) implants were investigated radiographically by
      quantitative digital subtraction analysis and by assessment of marginal bone
      height, with the aid of a computerized method. A loss of approximately 1 mm of
      marginal bone height was observed for both the dense Polyactive and the HA
      implants, after 6 months of loading. This value appeared to be stable from 12
      weeks of loading onward. Along the total length of the implant during the first 6
      weeks of loading, both the flexible (dense Polyactive) and the rigid (HA)
      implants showed a decrease in density. However, after this 6-week period, the
      bone density around the implants increased, and after 18 weeks the original bone
      density was reached. The flexible Polyactive implants provoked less decrease in
      density than the rigid HA implants, although not to a statistically significant
      level. This finding sustains the hypothesis that flexible implant materials may
      transfer stresses to the surrounding bone more favorably.

PMID- 9151173
TI  - Influence of implant diameters on the integration of screw implants. An
      experimental study in rabbits.
AB  - The influence of diameter on the integration of titanium screw-shaped implants
      was studied in the rabbit tibia by means of removal torque measurements and
      histomorphometry. Implants 3.0, 3.75, 5.0, and 6.0 mm in diameter and 6.0 mm long
      were inserted through one cortical layer in the tibial metaphyses of nine rabbits
      and allowed to heal for 12 weeks. The implants were then unscrewed with a torque
      gauge, and the peak torque required to shear off the implants was recorded. The
      histologic analysis in undemineralized ground sections comprised (1) a gross
      description of the implant sites and assessments of (2) the total implant length
      in bone and (3) in the cortical passage, as well as (4) the thickness of the
      cortical bone adjacent to the implants. From the removal torque values obtained
      and morphometric measurements, a mean shear stress value was calculated for each
      implant type. The biomechanical tests showed a statistically significant increase
      of removal torque with increasing implant diameter. The resistance to shear
      seemed to be determined by the implant surface in supportive cortical bone,
      whereas the newly formed bone at the periosteal and endosteal surfaces did not
      seem to have any supportive properties after 12 weeks. It is suggested that wide
      diameter implants may be used clinically to increase implant stability.

PMID- 9151174
TI  - Histologic and histometric evaluation of rat alveolar wound healing around
      polyurethane resin implants.
AB  - The biocompatibility of polyurethane resin-implants derived from castor bean
      (Ricinus communis) was analyzed in the rat dental alveolus. Histometric
      evaluation of trial areas adjacent to the implants showed, by week 1, the polymer
      granules encircled by a conspicuous capsule and surrounded by immature connective
      tissue. By weeks 2 and 3, the implants were surrounded by less prominent fibrous
      capsules and most of the tested area was occupied by mature trabecular bone. By
      week 6, the fibrous capsule was thinner and the tested area was almost totally
      covered with bone, which in several places was in close contact with the
      implants. The results suggest that the material is compatible, as it was
      progressively integrated into alveolar bone in the wound-healing process.

PMID- 9151175
TI  - The frequency, prognosis and significance of nerve injuries in total hip
      arthroplasty.
AB  - Although the incidence of post-operative nerve palsy after total hip replacement
      is rare, it is an important complication for the patient. In a retrospective
      study the results of 2713 hip arthroplasties were reviewed. Sixty-one cases
      (2.24%) of post-operative neuropathy were identified. 13 of the sciatic nerve, 33
      of the peroneal nerve and 15 of the femoral nerve. The risk is significantly
      higher in revisions (3.06%), especially when exchanging the acetabular component
      (8.5%) rather than in primary arthroplasties (2.13%). After an average period of
      107 months (11-240) from operation, 41 patients with nerve lesions were
      questioned about their subjective functional capacity: 17% had recovered
      completely, 39% had noticed an improvement, and in 44% there was no change; 56.1%
      complained of weakness and had a complete paralysis. In all cases there was
      dysfunction of sensibility. Another 17.1% had a sensibility defect without
      weakness. There was pain in 51.2%, paraesthesia in 34.1% and areas of complete
      anaesthesia in 19.5%. Altogether 61% of the 41 patients had either gait problems
      or were dependent on orthotic devices. In summary, only about a third of the
      patients studied achieved a satisfactory degree of functional recovery.

PMID- 9151176
TI  - Anterior instrumentation in idiopathic scoliosis: a minimum follow-up of 10
      years.
AB  - One hundred and thirty-four patients with idiopathic scoliosis were treated
      between 1973 and 1993 in our hospital, and 53 were followed for a minimum of 10
      years in a retrospective study. Forty-five were female and 8 male with an average
      age of 32 years at follow up. Dwyer instrumentation was used in 17 and Zielke in
      36. The curve was thoracic in 16, thoracolumbar in 27 and lumbar in 10. The
      average preoperative Cobb angle was 64 degrees. The average angle at follow up
      was 21 degrees with 62% of the average correction maintained (61% in the Dwyer
      and 65% in the Zielke). Most patients were satisfied subjectively and we
      recommend this type of operation.

PMID- 9151177
TI  - Magnetic resonance chemical shift imaging in bone and soft tissue tumours.
AB  - A study was carried out in 14 patients to assess the location and differential
      diagnosis of bone and soft tissue tumours with a 0.5 Tesla scanner, using water
      and fat images obtained by the three-point Dixon technique. We compared the
      magnetic resonance imaging findings obtained with this technique with
      conventional MRI, T1-T2-weighted images, and gadalinium-diethylenetriamine penta
      acetic acid enhanced T1-weighted images. Localisation was better with the three
      point Dixon technique than with conventional magnetic resonance imaging.
      Differentiation between the fat and water component around the tumour was
      possible. The gadalinium-diethylenetriamine penta-acetic acid enhanced water
      images were very sensitive to enhancement of the tissue. The three-point Dixon
      technique is useful when the tumour area is difficult to detect by conventional
      magnetic resonance imaging and information about its components is needed; these
      images can be made at the low magnet field.

PMID- 9151178
TI  - Massive osteolysis induced by high molecular weight polyethylene wear debris.
AB  - We investigated the mechanism by which particulate wear debris of polyethylene
      may induce bone resorption using an in vivo model. Two uncemented total hip
      prostheses, in which the socket was directly in contact with acetabular bone,
      were selected because there was massive bone loss around the implant. A thick
      synovium-like layer was found at the polyethylene-bone interface during revision
      operations. Samples were examined by transmitted and polarised light microscopy,
      and by transmission electron microscopy. This study demonstrates that
      polyethylene wear products alone can cause massive osteolysis by triggering the
      formation of foreign body granuloma at the bone-implant interface.

PMID- 9151179
TI  - Vertebral lesions associated with palmoplantar pustulosis.
AB  - Spinal lesions were reviewed in 9 patients (3 men and 6 women) who presented with
      palmoplantar pustulosis. Cervical lesions were found in 3 patients and
      lumbosacral involvement in 7. The duration of disease averaged 4.8 years. Seven
      patients had associated sterno-costo-clavicular hyperostotic lesions, and all
      showed abnormalities in blood tests which suggested chronic inflammation.
      Vertebral lesions were assessed as a spondylodiscitis type in 4, single level
      syndesmophyte-forming type in 1, multiple hyperostosis type in 4, and an ivory
      vertebra type in 1. Five patients were treated conservatively, and 4 with
      progressive spondylodiscitis type lesions underwent curettage and anterior
      interbody fusions. At follow-up, all patients improved in both spinal and
      cutaneous presentations, and 4 who underwent surgery and 1 with tonsillectomy
      attained complete cure. The vertebral manifestations of palmoplantar pustulosis
      may vary, but rapidly progressive lesions need surgery for favourable early
      improvement from the vertebro-cutaneous symptom complex.

PMID- 9151180
TI  - Uncemented revision stem for biological osteosynthesis in periprosthetic femoral
      fractures.
AB  - Fractures around a femoral prosthesis have been treated with plating and
      additional cement, but this leads to further reduction of bone stock in the
      proximal femur. Since February 1992, we have dealt with this problem in 12
      patients by revision using a long uncemented stem and distal interlocking
      combined with homologous bone grafting. Bony ingrowth and remodelling led to
      restoration of the proximal femur. After bone healing, removal of the distal
      interlocking screws converts the distal load transfer to the proximal anchoring
      of the revision stem so that osteointegration can occur in the trochanteric
      region. The clinical results were good in all the patients after a mean follow up
      of 23.5 months. This is a method which provides biological osteosynthesis and is
      especially indicated in younger patients.

PMID- 9151181
TI  - Changes in bone mineral density around a stable uncemented total hip
      arthroplasty.
AB  - Changes in bone mineral density (BMD) around the components of the Zweymueller
      total hip arthroplasty were measured, using dual energy X-ray absorptiometry, in
      36 women who were operated on for primary osteoarthritis. Seven regions of
      interest were studied. No changes occurred around the screw socket and the
      greater trochanter: but there was a significant reduction of BMD, only when
      measured immediately after the operation at the lesser trochanter and at the
      distal femoral cortex lateral and medial to the tip of the stem. These changes
      were not related to the age of the patients. The reduction of BMD in the femur
      was mostly associated with areas where bone had been removed at operation. The
      press-fit fixation of the Zweymueller stem and the maintenance of its fixation
      with time did not induce further bone turnover around it. The absence of changes
      in bone mineral density was due to the relatively small amount of subchondral
      removed and to the continued stable fixation of the socket.

PMID- 9151182
TI  - Quantitative assessment of callus distraction using dual energy X-ray
      absorptiometry.
AB  - Bone mineralisation during and after limb lengthening procedures on the femur or
      tibia using unilateral fixators has been monitored quantitatively using dual
      energy X-ray absorptiometry (DEXA). We measured the bone mineral density (BMD)
      prospectively in the newly formed callus, in the bone adjacent to the callus and
      in the proximal femur. In twenty-one patients we showed a typical course with a
      peak value at 4-6 weeks after beginning distraction and a minimum value at
      maximum distraction. In the consolidation period the BMD in the distraction gap
      increased until the fixator was removed. The BMD in the regenerated bone
      increased faster in the regions of interest (ROI) opposite the fixator compared
      to those near it. Dynamisation caused more homogeneous regeneration equalising
      VBMD in the different ROIs. The BMD in the proximal femur of the leg which was
      operated on decreased to 67% and in the opposite leg to 87% of the preoperative
      value. DEXA provides a precise and quantitative assessment of callus and bone
      mineralisation during limb lengthening and helps in understanding what is
      happening during these procedures.

PMID- 9151183
TI  - Extralesional resection for tumours of the pelvic bones.
AB  - A retrospective analysis of 92 patients with tumours of the bony pelvis is
      presented. Limbsparing operations may be adequate or inadequate. Adequate
      operations are those in which the excision is extralesional and the function of
      the limb is preserved as far as possible. An operation is inadequate if either
      oncological principles are abandoned or if carried out with no regard for them,
      but function is preserved to a greater extent. The postoperative mortality in 92
      patients was 1.2%. In 12, oncological principles were not fulfilled. Long term
      results were available in 78 patients: 42 are alive and free of disease after
      more than 5 years, 17 of them for more than 10 years and 2 for more than 25
      years. One patient with recurrence and metastases to the lungs is alive after 12
      years.

PMID- 9151184
TI  - Adherence of Staphylococcus aureus slime-producing strain variants to
      biomaterials used in orthopaedic surgery.
AB  - The adherence of Staphylococcus aureus to biomaterials used in orthopaedic
      surgery (polymethylmethacrylate, fresh bone, steel and titanium alloys) and to
      glass was studied in vitro at 1, 2, 6, 24 and 48 h of incubation. Nonslime
      producing strains (72, 80 and 510) and slime-producing variants of these strains
      were used. An automated and fast method of ATP-bioluminiscence was applied to
      determine bacterial viability. The lowest adherence corresponded to
      polymethylmethacrylate and bone, and the highest to metals. Significant adherence
      was detected in all cases after 6 h and was strain dependent, being lowest for
      strain 72. In most cases, adherence of nonslime-producing variants was not
      significant compared with controls, and slime-producing were more adherent than
      nonslime-producing variants. These differences were maximal at 6 h or 48 h,
      depending on the strain and the material. The findings suggest that the
      appearance of slime-producing cells within a given nonslime-producing bacterial
      population may jeopardise postoperative immune systems and antibiotic efficacy as
      a consequence of biofilm formation on implants and prostheses.

PMID- 9151185
TI  - A surgical technique for lengthening tight hamstring muscles in patients with low
      back pain.
AB  - An original technique for lengthening primary tight semitendinosus and
      semimembranosus muscles in their proximal portion is presented. The authors
      consider that primary shortening of these muscles rebounds on hip biomechanics
      and on the spine kinematics chain.

PMID- 9151186
TI  - Stress fracture of the femoral component in total knee replacement: a report of 3
      cases.
AB  - We report 3 cases of stress fracture of the femoral component (small size
      Whiteside Ortholoc II) in total knee replacements which occurred at 32, 52, and
      73 months after operation. The site was at the junction between the medial
      posterior bevelled surface and the posterior flange. The most likely cause of
      failure is due to the thinness of the metal at this point.

PMID- 9151187
TI  - Fracture of the neck of a femoral component in a total hip arthroplasty: a case
      report.
AB  - Fracture of components of a total hip arthroplasty occur is a recognised
      complication. We report an unusual case in which the fracture occurred through
      the neck of a femoral component on a Lord type of total hip arthroplasty.

PMID- 9151188
TI  - Bilateral demyelinating neuropathy in a solitary lytic and sclerotic myeloma of
      the proximal humerus: a case report.
AB  - Mixed lytic and sclerotic myeloma are uncommon and occur at an earlier age than
      multiple myeloma in areas of persistent haemopoiesis. Their characteristic
      symptoms are pain, swelling and pathological fractures and they are usually
      detected at an early stage. We report a case of a mixed sclerotic/lytic myeloma
      of the humerus presenting at an unusually advanced stage and associated with a
      bilateral progressive demyelinating peripheral sensory and motor polyneuropathy
      resembling polyradiculitis. The neurological changes partly disappeared after the
      tumour had been resected which suggests that nerve reconstitution may occur due
      to reversal of the demyelination.

PMID- 9151190
TI  - Comparison of albumin binding capacities of three different reactive dye
      derivatized poly(ethylene glycol dimethacrylate-hydroxyethyl methacrylate)
      microbeads.
AB  - Bovine serum albumin (BSA) adsorption onto dye-derivatized poly(ethylene glycol
      dimethacrylate-hydroxyethyl methacrylate) [poly(EGDMA-HEMA)] microbeads carrying
      three different reactive dye ligands (i.e. Congo Red. Cibacron Blue F3GA, and
      Alkali Blue 6B) was investigated. Swellable poly(EGDMA-HEMA) microbeads, in the
      size range of 150-200 microns, were produced by a modified suspension
      copolymerization of EGDMA and HEMA. The dyes were covalently attached to the
      microbeads. The maximum amounts of dye loadings were 14.5, 16.5, and 23.7 mumol g
      1 for Congo Red, Cibacron Blue F3GA, and Alkali Blue 6B, respectively. The
      maximum BSA adsorption on the dye-derivatized microbeads from aqueous solutions
      containing different amounts of BSA were 90, 60.5, and 40 mg g-1 for the Congo
      Red, Cibacron Blue F3GA, and Alkali Blue 6B carrying microbeads, respectively.
      The maximum BSA adsorptions were observed at pH 6.0 in all cases. Desorption of
      albumin molecules were achieved by using 1.0 M NaSCN (pH 8.0). High desorption
      ratios (more than 85% of the adsorbed BSA) were observed in all cases. It was
      possible to reuse these novel sorbents without significant losses in the
      adsorption capacities.

PMID- 9151189
TI  - Pre-incisional caudal epidural blockade and the relief of pain after lumbar spine
      operations.
AB  - We report the effect of pre-incisional caudal epidural injection of a mixture of
      20 ml 0.25% bupivacaine and 0.1 mg buprenorphine performed under general
      anaesthesia for relieving wound pain after posterior interbody fusion and
      laminotomy for spinal stenosis. Pain was compared in groups with and without
      blockade: 24 and 23 patients with fusion, and 30 and 28 with laminotomy
      respectively. In the first 12 h after each operation, the group with blockade
      required additional analgesics less frequently and had a lower visual analogue
      scale score than those without blockade. In, and after, the second 24 h patients
      with hypotension of 10 mm Hg, or more, after the blockade required additional
      analgesics less frequently than those without blockade for both operations and
      had a lower visual analogue score than those without blockade for laminotomy, but
      not for fusion. This is a simple procedure for relieving wound pain and in
      patients with hypotension caused by the block, the effect continued even after
      the analgesic action had disappeared.

PMID- 9151191
TI  - Enhanced hydrogel adhesion by polymer interdiffusion: use of linear poly(ethylene
      glycol) as an adhesion promoter.
AB  - The fracture energy required to separate layers of hydrogel films was
      investigated to evaluate the impact of bulk polymer diffusion on
      hydrogel/hydrogel adhesion and to obtain molecular information on the fracture
      energy in polymer mucoadhesion. Poly(ethylene glycol) (PEG) was incorporated in a
      hydrogel and was used as an adhesion promoter. The influence of PEG molecular
      weight and contact time on PEG diffusion across the hydrogel/hydrogel interface
      was investigated by using tensiometric studies and near-field FTIR microscopy.
      These experiments indicated that linear PEG diffusion enhanced the adhesion
      between the two hydrogel layers. The enhanced adhesion could not be explained by
      surface wetting phenomena alone. These results indicated that bulk diffusion of
      linear polymers such as PEG (adhesion promoter) incorporated into polymer
      networks (hydrogels) was an effective technique for enhancing gel/gel adhesion in
      various applications including polymer/mucus interactions in mucoadhesion and
      development of mucoadhesive controlled drug delivery systems.

PMID- 9151192
TI  - Synthesis and characterization of biodegradable polyrotaxane as a novel
      supramolecular-structured drug carrier.
AB  - Polyrotaxanes were synthesized as novel biodegradable polymers with
      supramolecular assembly and their properties evaluated in vitro. The synthesis of
      biodegradable polyrotaxanes consists of three steps: preparation of an inclusion
      complex consisting of alpha-cyclodextrins (alpha-CDs) and amino-terminated
      poly(ethylene glycol) (PEG); introduction of L-phenylalanine (L-Phc) at each
      complex terminal via peptide linkages: and hydroxypropylation of alpha-CDs in the
      polyrotaxanes. Succinimide ester of benzyloxycarbonyl-L-Phe was condensed with
      the terminal amino groups of the inclusion complex. 1H-NMR and GPC results showed
      that alpha-CDs were threaded onto a PEG chain and L-Phe moieties were introduced
      at each terminal of the PEG chain. Further, the amount of threaded alpha-CDs was
      found to be governed by the molecular weight of PEG. The hydroxypropylation of
      alpha-CDs improved the solubility of the polyrotaxanes in PBS (pH 7.4). The
      hydroxypropylated (HP-) polyrotaxanes were characterized by terminal peptide
      cleavage using papain. In vitro degradation of HP-polyrotaxanes revealed that HP
      alpha-CDs threaded onto a PEG chain were released only when terminal peptide
      linkages were cleaved. Moreover, threaded HP-alpha-CDs onto a PEG chain was found
      to be completely released. Kinetics of terminal peptide cleavage were also
      evaluated by catalytic efficiency (kcat/K(m)). The kcat/K(m) values were found to
      be independent of the molecular weight of HP-polyrotaxanes but to be affected by
      terminal hydrophobic moieties. It is proposed that our designed polyrotaxanes are
      feasible as novel drug carriers.

PMID- 9151193
TI  - Protein release from poly(epsilon-caprolactone) microspheres prepared by melt
      encapsulation and solvent evaporation techniques: a comparative study.
AB  - Poly(epsilon-caprolactone) (PCL) microspheres containing c. 3% bovine serum
      albumin (BSA) were prepared by melt encapsulation and solvent evaporation
      techniques. PCL, because of its low Tm, enabled the melt encapsulation of BSA at
      75 degrees C thereby avoiding potentially toxic organic solvents such as
      dichloromethane (DCM). Unlike the solvent evaporation method, melt encapsulation
      led to 100% incorporation efficiency which is a key factor in the
      microencapsulation of water-soluble drugs. Examination of the stability of the
      encapsulated protein by sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis (SDS-PAGE) demonstrated that protein integrity was unaffected by
      both methods of encapsulation. In vitro release of the protein into phosphate
      buffer examined at 37 degrees C from microspheres prepared by both techniques
      showed that the release rate from melt-encapsulated microspheres was somewhat
      slower compared to the release from solvent-evaporated spheres. Both released
      around 20% of the incorporated protein in 2 weeks amounting to approximately 6.5
      micrograms mg-1 of microspheres. Although the diffusivity of macromolecules in
      PCL is rather low, it is shown that PCL microspheres are capable of delivering
      sufficient quantity of proteins by diffusion for prolonged periods to function as
      a carrier for many vaccines. Unlike poly(lactic acid) (PLA) and poly(glycolic
      acid) (PGA) polymers which generate extreme acid environments during their
      degradation, the delayed degradation characteristics of PCL do not generate an
      acid environment during protein release and, therefore, may be advantageous for
      sustained delivery of proteins and polypeptides.

PMID- 9151194
TI  - Calcium effect on the membrane preparation of segmented
      poly(ether/urethane/amide) (PEUN) as a biomedical material.
AB  - Poly(ether/urethane/amide) (PEUN), a segmented polyurethane, was characterized
      concerning phase relationship, viscosity in solution, hydraulic permeability,
      mechanical properties, and in vivo biocompatibility with tissue and blood. PEUN
      was dissolved at the highest concentration of 0.5% in N,N-dimethylformamide
      (DMF). Addition of calcium chloride at concentrations up to 3.1% progressively
      increased the solubility of PEUN in DMF PEUN2 membrane was prepared by casting
      from mixtures of PEUN, 3% calcium chloride, and DMF, from which calcium chloride
      was sufficiently removed. The PEUN2 membrane thus obtained was compared with PEUN
      membrane which was prepared by casting from DMF solution without the addition of
      calcium chloride. The water permeability across PEUN2 membrane was higher than
      that across PEUN membrane. PEUN2 membrane in the swollen state exhibited a lower
      tensile modulus and much greater elastic property than PEUN membrane. Tissue
      compatibility of PEUN2 membrane was better than that of PEUN membrane.
      Thromboresistance of PEUN membrane was good, while PEUN2-coated surface was
      thrombogenic to some extent in vivo. Our characterization suggested that PEUN2
      membrane is more hydrophilic than PEUN membrane, possibly because of the assembly
      of polar groups on the segments of PEUN molecules which show affinity to calcium
      chloride in membrane processing.

PMID- 9151195
TI  - Comparison between in vitro and in vivo UHMW-PE degradation.
AB  - There is an increasing interest in orthopedics for clinical problems associated
      with wear and failure of ultra-high-molecular-weight (UHMW) polyethylene devices.
      Wear not only affects the implant performance but, more importantly, produces the
      release of particulate debris in the surrounding tissues and fluids. The debris
      in turn cause a deleterious biological response that can include an inflammatory
      reaction with subsequent loosening of the implant components. Surface wear is
      certainly promoted from the oxidation process that can occur during the
      prosthesis life. However, the oxidation mechanism involved during the
      implantation period has not been described yet for the UHMW-polyethylene devices.
      Here, the comparison of FT-IR spectra of a retrieved acetabular cup (9 years in a
      human body) and thin UHMW-PE films treated respectively with: H2O2, KO2/THF, and
      Fe[II]/H2O2 solutions indicates the effect of the high reactive hydroxyl radicals
      as the most important cause of in vivo polymer degradation.

PMID- 9151196
TI  - Diseases and injuries in athletes. A review.

PMID- 9151197
TI  - Effect of slow versus fast desaturation on the ventilatory response to hypoxia.
AB  - The ventilatory response to progressive hypoxia was studied in 15 healthy adult
      males by employing two different rates of desaturation. In a slow hypoxic ramp,
      peripheral oxygen saturation was gradually reduced to 70% over 10-13 min, while
      in a fast ramp the saturation was reduced over 3-5 min. The ventilatory response
      to hypoxia was evaluated as the slope of the regression between oxygen
      desaturation and minute ventilation (l/min/%). There was no significant
      difference in the slope between the slow and fast ramps. The subjects were
      further divided into two subgroups; namely high and low responders, according to
      the value of their slopes. A slope of 0.6 l/min/% was considered the cut-off
      limit for this classification. In the group of high responders, the hypoxic
      ventilatory response was significantly higher with the slow ramp than with the
      fast ramp (p < 0.05). In the low responders, the response was significantly
      higher with the fast ramp (p < 0.05). We conclude that the hypoxic ventilatory
      responses are influenced by the rate of desaturation and they appear to be
      related to the individual sensitivity to hypoxia. These responses are reversed in
      the low compared with the high responders.

PMID- 9151198
TI  - Survival of nosocomial pathogenic bacteria at ambient temperature.
AB  - Staphylococcus aureus and many gram-negative rods are prevalent nosocomial
      pathogens. The mechanisms by which these organisms persist and spread within the
      hospital environment have not been clearly defined. We found that these bacteria
      have an extraordinary capability for survival in the environment. The viabilities
      of staphylococcal and gram-negative (Escherichia coli and Pseudomonas aeruginosa)
      isolates were assessed on three environmental surfaces: a non-nutrient surface, a
      woven cotton fiber, and a blood protein coagulum. The bacteria were dried on
      these surfaces and quantitatively subcultured over six months. The viability was
      consistently higher on dried blood surfaces. Viability was next highest on cotton
      strings. For both of these environments, staphylococci appeared to lose viability
      between three and six months, while E. coli and P. aeruginosa survived longer.
      Survival on a clean non-nutrient surface (tubes alone) for all organisms was much
      briefer and did not extend beyond four weeks. Such extended survival on blood and
      fiber surfaces, as observed in part, explains the difficulty in controlling
      colonization of patients by and spread of these nosocomial pathogens.

PMID- 9151200
TI  - Increased leukocyte adhesiveness/aggregation is the single best biochemical
      indicator of disease activity in adolescent patients with inflammatory bowel
      disease.
AB  - We determined the relative utility of inflammatory markers in evaluating disease
      activity in adolescent patients with inflammatory bowel disease (IBD). Sixty-one
      adolescent patients and 50 age and sex matched volunteers who served as controls
      were evaluated prospectively. The erythrocyte sedimentation rate (ESR), C
      reactive protein (CRP), white blood cell count (WBCC), and the leukocyte
      adhesiveness/aggregation (LAA) test were determined in each patient. There were
      28 subjects in remission and 33 in relapse. Their percentage of aggregated white
      blood cells in the peripheral blood was 7 +/- 5 and 16 +/- 8, respectively, when
      compared with the control group (5 +/- 3) (p < 0.0001). Moreover, the LAA test
      was the only one which could effectively classify patients with IBD into their
      correct diagnostic categories of remission, mild-moderate, or moderate-severe
      disease activity. The LAA test is superior to other acute phase reactants used in
      daily practice to detect the presence of inflammation as well as for the
      assessment of its severity in adolescent patients with IBD. In addition, our
      findings may have biological relevance to the disease process and its potential
      manipulation by anti-adhesive agents.

PMID- 9151199
TI  - The pattern of inflammation in rat sepsis due to enterotoxin-producing
      Staphylococcus aureus: a comparison with ischemia-reperfusion injury.
AB  - Sepsis and trauma have similarities in their immunopathologic profiles. Both
      conditions can result in multi-system organ failure which is sometimes associated
      with cytokine generation and inflammatory cell activation. Furthermore, decreases
      in peripheral blood monocyte expression of HLA-DR have been noted in both human
      sepsis and trauma. However, the magnitude, onset, and time course of such stimuli
      are often difficult to ascertain in human studies. Thus, to study a more detailed
      in vivo immunologic profile in these conditions, rat models were employed. Our
      aim was to describe and analyze cytokine and peripheral blood immunophenotype
      patterns in bacterially induced rat sepsis and to compare this to rat ischemia
      reperfusion injury. Sprague-Dawley rats underwent either bacterial injection with
      enterotoxin producing Staphylococcus aureus or hind limb ischemia/ reperfusion.
      Two bacterial doses which were either lethal or sublethal at 24-48 hours were
      utilized. Peripheral blood neutrophils and B-lymphocytes were studied for
      expression of beta-integrins (CD11b and CD11b/c) and I-A, respectively, using
      flow cytometry. Corresponding plasma levels of TNF alpha and interferon gamma
      were measured by ELISA. At 24 hr, a lethal bacterial lethal bacterial dose
      injection resulted in significantly higher levels of neutrophil CD11b/c
      expression (p < 0.005) compared with ischemia-reperfusion treatment. B-cell I-A
      expression was also higher in lethal sepsis. Gamma interferon levels were
      significantly higher in lethal sepsis compared with ischemia-reperfusion (p =
      0.005). Studies over time showed that CD11b expression and interferon gamma were
      both more marked at 6 hr than at 24 hr in lethal sepsis. This pattern was not
      observed in sublethal sepsis or in ischemia-reperfusion. CD11b/c expression on
      the other hand remained elevated at comparable levels at 6 and 24 hr in lethal
      sepsis. B-cell I-A expression in ischemia-reperfusion and sublethal sepsis
      decreased at 24 hr compared with baseline. Lethal sepsis in rats injected with
      enterotoxin producing staphylococcus results in phasic alterations in neutrophil
      CD11b and plasma interferon levels prior to death. In analogy to the findings of
      monocyte decreases in DR expression observed in human trauma and sepsis, rat B
      cell I-A expression showed decreases in sublethal sepsis as well as in ischemia
      reperfusion injury. However, this was not observed in lethal sepsis. These
      findings have implications in understanding the immunologic/inflammatory changes
      observed in human sepsis and trauma.

PMID- 9151201
TI  - Ambulatory blood pressure measurement in type-II diabetic patients with autonomic
      neuropathy.
AB  - The aim of our study was to access the 24-hr ambulatory blood pressure (BP) in
      diabetic patients with autonomic neuropathy (AN). Twenty-two NIDDM patients
      without hypertension, being treated with sulfonylureas, were studied. The 24-hr
      ambulatory blood pressure recordings were performed using portable non-invasive
      automatic system. Autonomic neuropathy was assessed by standard cardiovascular
      reflex tests. There were ten patients with and 12 without AN, matched for age,
      body mass index, duration of diabetes and glycemic control. Mean BP increased at
      night in four of the subjects with AN and decreased in the remaining 18 patients.
      The group of subjects with nocturnal increases in BP had more severe autonomic
      nerve dysfunction compared with those with decreases in nocturnal BP. No
      significant difference between clinical and ambulatory day-time measurements was
      found. In three patients with AN after 5 weeks intensified therapy. 24-hr BP did
      not show any significant difference.

PMID- 9151202
TI  - Diabetic retinopathy and urinary albumin excretion rate in type II (non-insulin
      dependent) diabetic patients.
AB  - The aim of this study was to access the associations between urinary albumin
      excretion rate (AER) and diabetic retinopathy and its major risk factors in 105
      type II non-insulin-dependent diabetic (NIDDM) patients. In 44.7% of the
      patients, there were no signs of retinopathy (NR), whereas 30.4% had background
      (BR) and 24.7% proliferative retinopathy (PR). Patients with retinopathy, both BR
      and PR, were older and the duration of diabetes was longer, than in the group
      consisting of patients with NR. Patients with retinopathy had elevated AER (BR:
      9.4 +/- 2.8 micrograms/min, PR: 19.3 +/- 1.7 micrograms/min; vs. NR: 4.3 +/- 2.1
      micrograms/min, p < 0.001). Patients with retinopathy had a higher systolic blood
      pressure and the metabolic control was worse than those without retifiopathy. In
      the diabetic group as a whole, raised AER was correlated with the duration of
      diabetes (rs = 0.287, p < 0.01) and systolic blood pressure (rs = 0.269; p <
      0.01).

PMID- 9151203
TI  - A case report of pancreatic mucinous cystadenoma in a patient receiving chronic
      hemodialysis.
AB  - Cystic neoplasms of the pancreas are rare, accounting for about 9 to 10% of
      cystic pancreatic lesions. A 63-year-old man, who had been receiving chronic
      hemodialysis due to diabetic chronic renal failure, was admitted after the
      discovery of cystic masses in the pancreatic tail. Abdominal ultrasonography and
      computed tomography revealed multiloculated cystic tumors. Endoscopic retrograde
      cholangiopancreatography (ERCP) demonstrated findings consistent with malignant
      tumors. Preoperatively, he was thought to have a cystadenocarcinoma in the
      pancreatic tail for which he underwent a distal pancreatectomy and splenectomy.
      Histologic analysis of the resected mass established the diagnosis mucinous
      cystadenoma. To our knowledge, pancreatic mucinous cystadenoma occurring in a
      patient receiving chronic hemodialysis has not been previously reported.
      Therefore, we present a novel case in this report.

PMID- 9151204
TI  - Essential thrombocythemia following polycythemia vera: an unusual sequence.
AB  - Myeloproliferative disorders (MPD) are prone to modification and evolution during
      the progression of the disease. While post-polycythemia myeloid metaplasia and
      chronic myelogenous leukemia following polycythemia vera have been frequently
      described, no report is available about the evolution of polycythemia vera into
      essential thrombocythemia. Our case is probably the first report on this
      occurrence. In the course of a fortuitous observation of electrocardiographic
      alterations, a diagnosis of polycythemia vera was ruled out in accordance with
      polycythemia vera study group criteria. At the time of diagnosis, RBC was 6 x
      10(12)/L, WBC 15 x 10(9)/L, Ht 59% and platelets 1000 x 10(9)/L. The patient was
      treated with phlebotomies and radioactive phosphorus achieving a good remission
      or the disease. Five years later, platelets rose to over 3300 x 10(9)/L without
      significant modification or RBC, WBC and Ht. The restaging or the disease was
      consistent for an essential thrombocythemia. In particular, RBC mass was within
      normal levels. During the last ten years, the patient has been followed
      recurrently and the blood picture remained stationary, without an increase in the
      hematocrit but with a platelet count between 658 and 800 x 10(9)/L. We conclude
      that this report may complete data concerning the evolution of MPD in others.

PMID- 9151205
TI  - Peri-operative chylous ascites.
AB  - Chylous ascites occurs when lymphatics are disrupted due to primary lymphatic
      disease, infection, malignancy, or chronic liver disease. It may also occur
      following inadvertent interruption of abdominal lymphatics during surgery
      involving retroperitoneal dissection. It is suggested by some that during liver
      transplantation, severed hepatic lymphatics should be ligated or stented to avoid
      post-operative pleural and abdominal accumulation of chylous fluid. The
      occurrence of chylous ascites and the need to ligate lymphatics after orthotopic
      transplantation was assessed in 180 consecutive patients subjected to this
      procedure. Pre-operative chylous ascites present in one patient resolved
      following transplantation. Three patients who required retroperitoneal dissection
      to complete the biliary anastomosis via choledochojejunostomy or perform a
      hepatic artery graft developed post-operative chylous ascites which rapidly
      resolved without complications. These findings indicate special attention to
      transacted hepatic lymphatics is not required during orthotopic liver
      transplantation. Chylous ascites rarely occurs after liver transplantation and
      its transitory development is due to retroperitoneal dissection.

PMID- 9151206
TI  - G-proteins and insulin signaling.

PMID- 9151208
TI  - Some reflections on the early days of sequence searching.
AB  - Russell Doolittle is a biocomputing pioneer who was among the first to use
      computers in the 1960s to compare sequences. He contributed to the discovery of
      unforeseen sequence similarities, such as the relationship between v-src and v
      mos. Doolittle's reflection demonstrates the enormous advances made in
      bioinformatics, soft- and hardware, and the concurrent explosion in data storage
      and acceleration of communication. Today's advanced technology was not available
      at the beginning of Doolittle's career, when no databases existed, and
      researchers knew by heart most of the sequences which had been published.

PMID- 9151207
TI  - Cell cycle and apoptosis: possible roles of Gadd45 and MyD118 proteins inferred
      from their homology to ribosomal proteins.
AB  - The function and structure of many disease gene products are currently poorly
      understood, and the easiest way to proceed is to search databases for homologous
      proteins to infer function or structure from the closest database match.
      Bioinformatics provides a variety of methods that reach beyond the standard
      database searches with single query sequences. The identification of a large
      superfamily of ribosome-associated proteins by computer analysis enabled Eugene
      Koonin to infer functional information for Gadd45, which is part of a cell-cycle
      checkpoint pathway defective in ataxia-telangiectasia.

PMID- 9151209
TI  - Naked DNA for vaccine or therapy.

PMID- 9151210
TI  - Gene therapy: from retrovirus to triplex DNA repair.

PMID- 9151212
TI  - Specific cytotoxic T lymphocytes in gene therapy.
AB  - Cytotoxic T lymphocytes possess the capacity to lyse target cells which express
      antigens on their surface recognized by the T cell receptor. These cells are
      crucial in the body's defense against foreign antigens. It has long been a goal
      of tumor biology to utilize T cells specialized in the elimination of unwanted
      cells for the treatment of cancer. The killing activity of T lymphocytes is
      restricted to specific antigen-presenting cells. For this reason the use of
      cytotoxic T cells in the elimination of cancer cells is limited to cancer cells
      which present neoantigens on their surface. To circumvent this limitation we
      describe a procedure in which the zeta component of the T cell receptor is
      genetically manipulated and equipped with an extracellular recognition domain.
      Introduction of a chimeric gene, consisting of the zeta chain of the T cell
      receptor and a single-chain antibody domain, into cytotoxic T lymphocytes results
      in T cells with a predetermined recognition specificity for particular tumor
      cells. The MHC restriction of target cell recognition can be avoided and tumor
      cells recognized by the single chain antibody domain can be recognized and lysed.
      Retroviral-mediated gene transduction was used to introduce chimeric zeta chain
      constructs into primary T cells of mice. The cocultivation of retrovirus
      producing helper cells with in vitro activated T lymphocytes led to a high gene
      transduction efficiency into primary T cells. These primary T cells assumed a
      predetermined specificity for target cell recognition and lysis. The production
      and provision of tumor cell specific T lymphocytes might not be sufficient to
      eradicate large tumors in vivo. Using a Schwannoma cell line, we showed that
      transplanted tumors secrete transforming growth factor beta and thereby stifle
      the action of lymphocytes. We suggest that a coordinated strategy including the
      suppression of tumor cells specific antilymphocyte action and the provision of
      tumor cell specific T cells might be required to successfully eliminate tumor
      cells in vivo.

PMID- 9151211
TI  - Biosynthetic retrovectoring systems for gene therapy.
AB  - Chemical and physical methods of introducing genes into cells (transfection) are
      being combined with viral transduction as one possible approach toward overcoming
      the shortcomings of current gene transfer methods. Although several different
      strategies are being developed worldwide, this article focuses on modification of
      retroviral vectoring systems. One goal of this work is to combine the safety and
      ease of transfection methods with the permanency that is presently achieved only
      by integrating viruses. Work with retrotransposon pseudotypes, synthetic
      retrovectors, and liposomal delivery of retrovirus vectors is discussed.

PMID- 9151213
TI  - Triplex DNA: fundamentals, advances, and potential applications for gene therapy.
AB  - The ability to target specific sequences of DNA through oligonucleotide-based
      triple-helix formation provides a powerful tool for genetic manipulation. Under
      experimental conditions, triplex DNA can inhibit DNA transcription and
      replication, generate site-specific mutations, cleave DNA, and induce homologous
      recombination. This review describes the binding requirements for triplex
      formation, surveys recent advancements in the chemistry and biology of triple
      helices and considers several potential applications of triplex DNA for use in
      genetic therapy.

PMID- 9151214
TI  - Conditional, tissue-specific expression of Q205L G alpha i2 in vivo mimics
      insulin action.
AB  - Deficiency of the G protein subunit G alpha i2 that is known to mediate the
      inhibitory control of adenylylcyclase impairs insulin action [11]. Using the
      promoter for the phosphoenolpyruvate carboxykinase gene, conditional tissue
      specific expression of the constitutively active mutant form (Q205L) of G alpha
      i2 was achieved in mice harboring the transgene. Expression of Q205L G alpha i2
      was detected in liver and adipose tissue of transgenic mice. Whereas the G alpha
      i2 deficient mice displayed blunted glucose tolerance, the Q205L G alpha i2
      expressing mice displayed enhanced glucose tolerance. Hexose transport and the
      recruitment of GLUT4, but not GLUT1, transporters to the membrane were elevated
      in adipocytes from Q205L G alpha i2 expressing mice in the absence of insulin.
      Additionally, hepatic glycogen synthase was found to be activated in Q205L G
      alpha i2 expressing mice, in the absence of the administration of insulin. Serum
      insulin levels in transgenic mice fasted overnight were equivalent to those of
      their control littermates. These data demonstrate that much as G alpha i2
      deficiency leads to insulin resistance, expression of Q205L constitutively active
      G alpha i2 mimics insulin action in vivo, reflecting a permissive role of G alpha
      i2 in signaling via this growth factor receptor tyrosine kinase linked pathway.

PMID- 9151215
TI  - Induction of tumor-specific cytotoxic T lymphocytes by immunization with
      autologous tumor cells and interleukin-2 gene transfected fibroblasts.
AB  - In a phase I trial designed to study a vaccine composed of autologous tumor cells
      and interleukin-2 gene transfected fibroblasts we analyzed lymphocytes
      infiltrating the vaccination site (VIL) in two melanoma patients. Functional
      studies demonstrated that numbers of MHC class I restricted cytotoxic T cells
      directed against the autologous tumor had increased at the immunization site in
      both cases. Analysis of the variability of T cell receptors (TCR) in the VIL of
      one patient revealed that the cytotoxic T lymphocytes consisted of a predominant
      population of TCRBV21S3+ T cells. Enrichment of this subpopulation to more than
      99% by specific anti-TCRBV21S3 monoclonal antibody linked immunomagnetic beads
      and sequencing of the TCR-beta chain disclosed exactly the same V-D-J junctional
      sequence in all eight TCRBV21 transcripts from these VIL. The identical sequence
      was also detected in all eight TCRBV21 transcripts from the patient's tumor
      infiltrating lymphocytes, indicating that the same CTL clone had infiltrated the
      tumor, circulated in the peripheral blood, and was amplified at the vaccination
      site. The TCRBV21S3+ T cells were also found to display an MHC class I restricted
      cytotoxic activity specifically directed against the autologous tumor cells. At
      the beginning of treatment these cells were undetectable at the vaccination site
      and delayed-type hypersensitivity testing was negative, contrasting with the
      positive results after therapy. Thus it is likely that vaccination with
      autologous tumor cells plus interleukin-2 gene transfected allogeneic fibroblasts
      had induced not only local accumulation but also an increase in the frequency of
      circulating tumor specific CTL.

PMID- 9151216
TI  - Phase I study to the immunotherapy of metastatic malignant melanoma by a cancer
      vaccine consisting of autologous cancer cells transfected with the human IL-2
      gene.

PMID- 9151218
TI  - Boron neutron capture therapy of brain tumors--current status and future
      prospects.

PMID- 9151217
TI  - Gene therapy for glioblastoma [correction of gliobestome] multiform: in vivo
      tumor transduction with the herpes simplex thymidine kinase gene followed by
      ganciclovir.

PMID- 9151219
TI  - The rationale and requirements for the development of boron neutron capture
      therapy of brain tumors.
AB  - The dismal clinical results in the treatment of glioblastoma multiforme despite
      aggressive surgery, conventional radiotherapy, and chemotherapy, either alone or
      in combination has led to the development of alternative therapeutic modalities.
      Among these is boron neutron capture therapy (BNCT). This binary system is based
      upon two key requirements: (1) the development and use of neutron beams from
      nuclear reactors or other sources with the capability for delivering high fluxes
      of thermal neutrons at depths sufficient to reach all tumor foci, and (2) the
      development and synthesis of boron compounds that can penetrate the normal
      bloodbrain barrier, selectively target neoplastic cells, and persist therein for
      suitable periods of time prior to irradiation. The earlier clinical failures with
      BNCT related directly to the lack of tissue penetration by neutron beams and to
      boron compounds that showed little specificity for and low retention by tumor
      cells, while attaining high concentrations in blood. Progress has been made both
      in neutron beam and compound development, but it remains to be determined whether
      these are sufficient to improve therapeutic outcomes by BNCT in comparison with
      current therapeutic regimens for the treatment of malignant gliomas.

PMID- 9151220
TI  - Early history of development of boron neutron capture therapy of tumors.
AB  - The stable isotope 10B has a peculiarly marked avidity to capture slow neutrons
      whereupon it disintegrates into a lithium and a helium atom. These give up the
      2.4 MeV of disintegration energy which they share within 5 and 9 microns of the
      10B atom respectively. This means that the cell closest to the 10B atom bears the
      brunt of its atomic explosion. The objective of the tumor therapist is to find a
      carrier molecule for the boron atom which will concentrate in the tumor. Although
      a number of investigators saw the peculiar advantage of this selective tactic to
      achieve destruction of a species of unwanted cells, no success in animal studies
      was achieved until 1950. Sweet and colleagues found that the capillary blood
      brain barrier keeps many substances out of the normal brain but that the gliomas
      had much less of such a barrier. He, Brownell, Soloway and Hatanaka in Boston
      together with Farr. Godwin, Robertson, Stickley. Konikowski and others at the
      Brookhaven. National Laboratory worked partially in collaboration and partly
      independently. We irradiated at 3 nuclear reactors several series of glioma
      patients with no long-term remission, much less a cure being achieved. Hatanaka
      on his return to Japan kept BNCT alive by treating a total of 140 patients with
      various brain tumors. Beginning in 1972, Mishima and colleagues have achieved
      useful concentrations of 10B-borono-phenylalanine, an analogue of the melanin
      precursor tyrosine, for BNCT of melanomas.

PMID- 9151221
TI  - The requirements and development of neutron beams for neutron capture therapy of
      brain cancer.
AB  - One of the two overriding conditions for successful BNCT is that there must be a
      sufficient number of thermal neutrons delivered to each of the boronated cells in
      the tumour bed (target volume). Despite the poor experience with BNCT in the USA
      some 40 years ago, the continued apparent success of BNCT in Japan since 1968,
      lead indirectly to the re-start of clinical trials on BNCT in 1994 at both
      Brookhaven and MIT. Similar trials will start soon at Petten in Europe. At other
      centres worldwide, many neutron beam designs are being proposed with either
      thermal or epithermal neutrons, emanating predominantly from nuclear research
      reactors. It is apparent that whilst the success of BNCT depends on a suitable
      neutron beam, there is a diversity in available designs, as well as each proposed
      type of neutron source, with consequently different characteristics of the
      emergent neutron beam. The paper presents the historical development of neutron
      beams used for BNCT, addresses the requirements on the types of beams, describes
      some of the existing designs and other proposals elsewhere and lastly, considers
      the broader requirements in designing NCT facilities. The focus of the paper is
      on treatment of brain cancer, neutron beam requirements for other types of cancer
      may vary.

PMID- 9151223
TI  - Liposomes as drug delivery vehicles for boron agents.
AB  - The successful treatment of cancer by boron neutron capture therapy (BNCT)
      requires the selective concentration of boron-10 within malignant tumors. The
      potential of liposomes to deliver boron-rich compounds to tumors has been
      assessed by examination of the biodistribution of boron delivered by liposomes in
      tumor-bearing mice. Small unilamellar vesicles have been found to stably
      encapsulate high concentrations of water-soluble ionic boron compounds.
      Alternatively, lipophilic boron-containing species have been embedded within the
      phospholipid bilayer of liposomes, and both hydrophilic and lipophilic boron
      compounds have been incorporated within the same liposome formulation. The
      biodistribution of boron was determined at several time points over 48 hr after
      i.v. injection of liposomal suspensions in BALB/c mice bearing EMT6 tumors. The
      tumor-selective delivery of boron by the liposomes was demonstrated as tumor
      boron concentrations increased for several hours post-injection. Even at the low
      injected doses employed (6-18 mg boron/kg body weight) therapeutic tumor boron
      concentrations were observed (> 30 micrograms boron/g tissue) and high
      tumor/blood ratios were achieved (> 5). The most favorable results were obtained
      with the polyhedral borane Na3[a2-B20H1-NH2CH2CH2NH2]. Liposomes encapsulating
      this species produced a tumor boron concentration of 45 micrograms/g tissue at 30
      hr post-injection, at which time the tumor/blood boron ratio was 9.3.

PMID- 9151222
TI  - Chemistry and biology of some low molecular weight boron compounds for boron
      neutron capture therapy.
AB  - Boronated DNA targeting agents are especially attractive candidates for BNCT
      because they may deliver boron-10 to the nuclei of tumor cells. Numerous boron
      containing analogs have been synthesized and some have shown promising results in
      initial biological tests. One of the most challenging tasks in this special field
      of research remains the finding of suitable targeting strategies for the
      selective delivery of boron rich DNA-intercalator/alkylator to tumor cells.
      Synthetic and biological studies of boron compounds suitable for DNA-binding are
      reviewed. The amino acid p-boronophenylalanine (BPA) is presently of considerable
      clinical interest. Other boronated amino acids might also be candidates for BNCT
      either per se, as part of part of tumor-seeking peptides or conjugated to
      targeting macromolecules. A large number of boronated L- and D-amino acids with
      varying liphophicility and sterical requirements are now available for
      evaluation. Recent synthetic and biological studies of aromatic boronoamino
      acids, carboranylamino acids and carboranyl amines are also reviewed.

PMID- 9151224
TI  - Enhanced survival of glioma bearing rats following boron neutron capture therapy
      with blood-brain barrier disruption and intracarotid injection of
      boronophenylalanine.
AB  - Boronophenylalanine (BPA) has been used for boron neutron capture therapy (BNCT)
      of brain tumors in both experimental animals and humans. The purpose of the
      present study was to determine if the efficacy of BNCT could be enhanced by means
      of intracarotid (i.c.) injection of BPA with or without blood-brain barrier
      disruption (BBB-D) and neutron irradiation using a rat brain tumor model. For
      biodistribution studies, F98 glioma cells were implanted stereotactically into
      the brains of Fischer rats, and 12 days later BBB-D was carried out by i.c.
      infusion of 25% mannitol (1.373 mOsmol/ml), followed immediately by i.c.
      administration of 300, 500 or 800 mg of BPA/kg body weight (b.w.). At the 500 mg
      dose a fourfold increase in tumor boron concentration (94.5 micrograms/g) was
      seen at 2.5 hours after BBB-D. compared to 20.8 micrograms/g in i.v. injected
      animals. The best composite tumor to normal tissue ratios were observed at 2.5
      hours after BBB-D, at which time the tumor: blood (T: Bl) ratio was 10.9, and the
      tumor: brain (T:Br) ratio was 7.5, compared to 3.2 and 5.0 respectively for i.v.
      injected rats. In contrast, animals that had received i.c. BPA without BBB-D had
      T : Bl and T:Br ratios of 8.5 and 5.9, respectively, and the tumor boron
      concentration was 42.7 micrograms/g. For therapy experiments, initiated 14 days
      after intracerebral implantation of F98 glioma cells, 500 mg/kg b.w. of BPA were
      administered i.v. or i.c. with or without BBB-D, and the animals were irradiated
      2.5 hours later at the Brook-haven Medical Research Reactor with a collimated
      beam of thermal neutrons delivered to the head. The mean survival time for
      untreated control rats was 24 +/- 3 days, 30 +/- 2 days for irradiate controls,
      37 +/- 3 days for those receiving i.v. BPA, 52 +/- 15 days for rats receiving
      i.c. BPA without BBB-D, and 95 +/- 95 days for BBB-D followed by i.c. BPA and
      BNCT. The latter group had a 246% increase in life span (ILS) compared to
      untreated controls and a 124% ILS compared to that of i.v. injected animals.
      These survival data are the best ever obtained with the F98 glioma model and
      suggest that i.c. administration of BPA with or without BBB-D may be useful as a
      means to increase the efficacy of BNCT.

PMID- 9151226
TI  - Microdosimetry for boron neutron capture therapy: a review.
AB  - A review of the microdosimetry of boron neutron capture therapy is presented
      focusing on the progression of key scientific ideas and developments in this
      field rather than on a comprehensive and inclusive review of the literature. The
      author concludes that from a microdosimetry perspective the field is highly
      advanced, but what is lacking is the correlation of the proposed models and
      results with experimental radiobiological data.

PMID- 9151225
TI  - A review: CNS effects and normal tissue tolerance in dogs.
AB  - Large animal studies have been utilized to define tolerance of normal brain to
      irradiation and verify treatment planning programs with two recently installed
      epithermal neutron beams. The normal brain tolerance studies utilized two
      biological endpoints, magnetic resonance visible damage only and neurologic signs
      progressing to death. The studies focused on defining the proton RBE for the
      contaminant fast neutrons, and from nitrogen capture of thermal neutrons and
      boron capture reaction biologic effect. The proton RBE was approximately 3.0 to
      6.7, depending on whether a dose reduction factor for the low gamma dose rate was
      employed. The microscopic distribution of the boron compounds, coupled with the
      extremely short length of the fission fragments from thermal neutron capture by
      10B yields an observed biologic effect much less than would be expected from such
      high LET irradiation. This observed biologic effect, which is a product of the
      microdistribution of the boron atom and the relative biologic effect of the
      fission fragments has been termed compound factor. The compound factor was based
      on the calculated physical dose from the fission fragment in blood based on
      measured blood 10B concentration. The approximate compound factor for BSH was
      studied at the two institutions and it ranged from 0.27 to 0.55, depending on the
      site and the endpoint chosen. The mean compound factor for BPA was only studied
      at one site and was found to be 1.1 for both endpoints. The increase in the
      compound factor for BPA is in keeping with previous calculations based on the
      differences in compound distribution. Results of these studies has helped the
      initiation of phase I and phase II clinical trials at Brook haven National
      Laboratory and the planned European clinical trials at Petten, The Netherlands.

PMID- 9151227
TI  - Computational dosimetry and treatment planning for boron neutron capture therapy.
AB  - The technology for computational dosimetry and treatment planning for Boron
      Neutron Capture Therapy (BNCT) has advanced significantly over the past few
      years. Because of the more complex nature of the problem, the computational
      methods that work well for treatment planning in photon radiotherapy are not
      applicable to BNCT. The necessary methods have, however, been developed and have
      been successfully employed both for research applications as well as human
      trials, although further improvements in speed are needed for routine clinical
      applications. Computational geometry for BNCT applications can be constructed
      directly from tomographic medical imagery and computed radiation dose
      distributions can be readily displayed in formats that are familiar to the
      radiotherapy community.

PMID- 9151228
TI  - Boron neutron capture therapy. Clinical brain tumor studies.
AB  - Since 1968, we have treated 149 patients and performed boron-neutron capture
      therapy (BNCT) on 164 occasions using 5 reactors in Japan. There were 64 patients
      with glioblastoma, 39 patients with anaplastic astrocytoma and 17 patients with
      low grade astrocytoma (grade 1 or 2). There were 30 patients with other types of
      tumor. The overall response rate in the glioma patients was 64%. Seven patients
      (12%) of glioblastoma, 22 patients (56%) of anaplastic astrocytoma and 8 patients
      (62%) of low grade astrocytoma lived more than 2 years. Median survival time of
      glioblastoma was 640 days. Median survival times of patients with anaplastic
      astrocytoma was 1811 days, and 1669 days in low grade astrocytoma. Six patients
      (5 glioblastoma and one anaplastic astrocytoma) died within 90 days after BNCT.
      Six patients (two glioblastoma and four anaplastic astrocytomas) lived more than
      10 years. Histological grading, age of the patients, neutron fluence at the
      target point and target depth or size of the tumor were proved to be important
      factors. BNCT is an effective treatment for malignant brain tumors. We are now
      able to radiate the tumor more correctly with a high enough dose of neutron beam,
      even if we use thermal neutron beam.

PMID- 9151229
TI  - Pharmacokinetics and boron uptake of BSH (Na2B12H11SH) in patients with
      intracranial tumors.
AB  - We evaluated retrospectively the pharmacokinetics and boron uptake of BSH
      (mercaptoundecahydrododecarborate) for Boron Neutron Capture Therapy (BNCT) in
      123 patients undergoing craniotomy for intracranial tumors. The pharmacokinetics
      revealed that BSH could move easily from blood to the peripheral organs; it was
      retained there and elimination was very slow. BSH after intra-arterial infusion
      (i.a.) was found to move into the peripheral organs more easily than after intra
      venous (i.v.) infusion. In patients with malignant glioma, the average values of
      boron concentration in tumor and the tumor to blood ratio (T/B ratio) after i.a.
      infusion were 26.8 +/- 19.5 micrograms/g (range, 6.1-104.7 micrograms/g) and 1.77
      +/- 1.30 (range, 0.47-6.65) respectively. On the other hand, after i.v. infusion
      the values were 20.9 +/- 12.2 micrograms/g (range, 7.0-39.7 micrograms/g) and
      1.30 +/- 0.65 (range, 0.61-2.94) respectively. The differences are not
      statistically significant. Boron uptake in malignant glioma was about three times
      higher than low grade glioma. We found a good correlation between boron uptake
      and time interval from BSH infusion, and 15-20 hours after BSH infusion the boron
      concentration in tumor was above 20 micrograms/g 10B in 69% of the malignant
      glioma patients; T/B ratio was above one in 75%, and above two in 44% of them. We
      recommend intra-venous infusion of BSH clinically since it is safer, and results
      in sufficient boron concentration in tumor, and the planned irradiation might be
      optimal around 15-20 hours after the BSH infusion for treating malignant glioma.

PMID- 9151231
TI  - Boron neutron capture therapy for glioblastoma multiforme using p
      boronophenylalanine and epithermal neutrons: trial design and early clinical
      results.
AB  - A Phase I/II clinical trial of boron neutron capture therapy (BNCT) for
      glioblastoma multiforme is underway using the amino acid analog p
      boronophenylalanine (BPA) and the epithermal neutron beam at the Brook-haven
      Medical Research Reactor. Biodistribution studies were carried out in 18 patients
      at the time of craniotomy using an i.v. infusion of BPA, solubilized as a
      fructose complex (BPA-F). There were no toxic effects related to the BPA-F
      administration at doses of 130, 170, 210, or 250 mg BPA/kg body weight. The
      tumor/ blood, brain/blood and scalp/blood boron concentration ratios were
      approximately 3.5:1, 1:1 and 1.5:1, respectively. Ten patients have received BNCT
      following 2-hr infusions of 250 mg BPA/kg body weight. The average boron
      concentration in the blood during the irradiation was 13.0 +/- 1.5 micrograms
      10B/g. The prescribed maximum dose to normal brain (1 cm3 volume) was 10.5 photon
      equivalent Gy (Gy-Eq). Estimated maximum and minimum doses (mean +/- sd, n = 10)
      to the tumor volume were 52.6 +/- 4.9 Gy-Eq (range: 64.4-47.6) and 25.2 +/- 4.2
      Gy-Eq (range: 32.3-20.0), respectively). The estimated minimum dose to the target
      volume (tumor +2 cm margin) was 12.3 +/- 2.7 Gy-Eq (range: 16.2-7.8). There were
      no adverse effects on normal brain. The scalp showed mild erythema, followed by
      epilation in the 8 cm diameter field. Four patients developed recurrent tumor,
      apparently in the lower dose (deeper) regions of the target volume, at post-BNCT
      intervals of 7,5,3.5 and 3 months, respectively. The remaining patients have had
      less than 4 months of post-BNCT follow-up. BNCT, at this starting dose level,
      appears safe. Plans are underway to begin the dose escalation phase of this
      protocol.

PMID- 9151230
TI  - Binding and distribution of Na2B12H11SH on cellular and subcellular level in
      tumor tissue of glioma patients in boron neutron capture therapy.
AB  - To determine binding and distribution of Na2B12H11SH (BSH) in glioma tissue in
      case of boron neutron capture therapy, an antibody to this compound was produced
      and used in immunohistochemical investigations. It is possible to trace BSH in
      immunohistochemistry, because BSH is firmly bound to the glioma tissue. The
      antibody against BSH is specific for that antigen, as tumor tissue from patients
      without BSH administration did not stain. In areas of healthy brain from BSH
      infused patients, no staining of tissue was detectable. In tumor tissues, BSH is
      presenting as a strong staining in cytoplasm and nucleus areas.

PMID- 9151232
TI  - The role of boron MRI in boron neutron capture therapy.
AB  - Boron magnetic resonance imaging (MRI) and spectroscopy (MRS) are being developed
      for use in boron neutron capture therapy (BNCT). With continued development,
      boron MRI may be used to locate BNCT agents in vivo, evaluate the
      pharmacokinetics of BNCT agents, and aid in treatment planning.

PMID- 9151233
TI  - In vivo diagnosis of human malignant melanoma with positron emission tomography
      using specific melanoma-seeking 18F-DOPA analogue.
AB  - Detection and diagnosis of human malignant melanoma by Positron Emission
      Tomography (PET) using 18F-10B-L-BPA, a specific melanogenesis-seeking compound
      synthesized for use in Boron Neutron Capture Therapy for malignant melanoma
      (NCT), has been developed. This resulted in a novel, highly effective methodology
      for the selective three dimensional imaging of metastatic malignant melanomas,
      and for accurate determination of 10B concentration in the tumor and surrounding
      tissue, providing almost all diagnostic information necessary for complete non
      invasive radiation dose planning in the treatment of malignant melanoma both for
      NCT as well as other therapeutic modalities.

PMID- 9151235
TI  - Strategic planning workshop on research needs for neutron capture therapy.
AB  - The workshop 'Research Needs for Neutron Capture Therapy', held in Williamsburg,
      VA, May 9-12. 1995 addressed key issues and questions related to optimization of
      boron neutron capture therapy (BNCT), in general, and to the possibility of
      success of the present BNCT trials at the Brookhaven National Laboratory (BNL)
      and Massachusetts Institute of Technology (MIT), in particular. Both trials use
      nuclear fission reactors as neutron sources for BNCT of glioblastoma multiforme
      (BNL) and of deep seated melanoma (MIT). Presentations and discussions focussed
      on optimal boron-labeled compounds, mainly for brain tumors such as glioblastoma
      multiforme, and the best mode of compound delivery to the tumor. Also, optimizing
      neutron irradiation with dose delivery to the tumor cells and the issues of
      dosimetry of BNCT especially in the brain were discussed. Planning of treatment
      and of follow-up of patients, coordination of BNCT at various treatment sites,
      and the potential of delivery BNCT to various types of cancer with an
      appropriately tailored protocol were additional issues. The need for multicentric
      interdisciplinary cooperation among the different medical specialties was
      highlighted.

PMID- 9151234
TI  - Boron neutron capture enhanced fast neutron radiotherapy for malignant gliomas
      and other tumors.
AB  - Both fast neutron radiotherapy and boron neutron capture therapy have been
      investigated as new radiation treatment techniques for patients with malignant
      gliomas. While each of these techniques individually has shown the potential for
      pathological eradication of malignant glioma, to date neither has evolved into an
      accepted, improved method of treatment. We have recently begun a research program
      investigating the feasibility of combining the benefits of both types of therapy.
      As a fast neutron beam penetrates tissue some of the particles are degraded to
      thermal energies. These can be captured by 10B or other suitable isotopes
      resulting in a highly-localized release of additional energy during a course of
      fast neutron radiotherapy. In this article we will review the rationale for such
      an approach, and review the underlying physics as well as in vitro, in vivo, and
      early human studies testing its feasibility. If appropriate carrier agents can be
      found that preferentially-localize in tumor cells, this approach ena be applied
      to many different tumor systems.

PMID- 9151236
TI  - Evaluation of the changes in serum lipid profile and ferritin concentrations in
      relation to body ascorbic acid status in healthy pre- and postmenopausal women.
AB  - The aim of this work was to study the relationship between body ascorbic acid
      (AA) status and serum lipid profile and ferritin concentrations in healthy pre-
      and postmenopausal women. The mean leukocyte and plasma ascorbate values in
      postmenopausal women were found to be significantly low but within acceptable
      ranges as compared to premenopausal women. According to these results, plasma and
      leukocyte AA concentrations decreased after the cessation of ovarian hormone
      production. In addition, significant increases in total cholesterol, triglyceride
      and LDL-cholesterol but a significant decrease in HDL-cholesterol were observed
      in postmenopausal women as compared to premenopausal women. A close positive
      relationship was found between plasma and leukocyte AA and body iron status in
      postmenopausal women. The findings were prominent especially in the subgroup of
      postmenopausal women with low body AA status. Thus, it is concluded that women
      having low body AA concentrations might have a predisposition for iron depletion.

PMID- 9151237
TI  - Hypoglycemic activity of to-kai-san (Chinese medicines) in normal and KK-Ay mice.
AB  - The hypoglycemic effect of To-Kai-San (TS) was studied in normal mice,
      streptozotocin-induced diabetic mice, one of the animal models of insulin
      dependent diabetes mellitus (IDDM) with hypoinsulinemia, and KK-Ay mice, one of
      the animal models of non-insulin-dependent diabetes mellitus (NIDDM) with
      hyperinsulinemia. TS (1,500 mg/kg) reduced the blood glucose of the KK-Ay mice
      from 441 +/- 36 to 285 +/- 52 mg/100 ml 7 h after a single oral administration (p
      < 0.001). However, no changes in blood glucose were observed in the normal and
      STZ-induced diabetic mice. TS also decreased the blood glucose 20 days after
      repeated administration to normal and KK-Ay mice. In addition, TS-treated KK-Ay
      mice showed decreased plasma insulin levels after both single and repeated
      administration. From these findings, it is believed that TS may require the
      presence of insulin to display its activity.

PMID- 9151238
TI  - Synthesis of monoesters of pyrroloquinoline quinone and imidazopyrroloquinoline,
      and radical scavenging activities using electron spin resonance in vitro and
      pharmacological activity in vivo.
AB  - Monoesters with the ester groups at C-2 of pyrroloquinoline quinone (PQQ) and C-9
      of imidazopyrroloquinoline (IPQ) were synthesized, and radical scavenging
      activities of coenzyme PQQ, IPQ compounds synthesized from PQQ and various amino
      acids, and monoesters of PQQ and IPQ were studied in vitro and in vivo. PQQ and
      PQQ monoesters had strong radical scavenging activity using ESR in in vitro
      experiments. The IC50 value for superoxide (O2-) was from 1 to 6 x 10(-8) M and
      that for the hydroxy radical (.OH) was from 4 to 6 x 10(-5) M. IPQ compounds and
      IPQ monoesters also showed radical scavenging activity. These compounds prevented
      injury during in vivo experiments, such as hydrocortisone-induced cataracts,
      endotoxin shock and CCl4-induced liver injury (isolated hepatocytes and rats).
      Especially, the monoesters of PQQ and IPQ prevented liver injury in rats equally
      by oral or intraperitoneal administration. These results suggest that PQQ
      functions as a radical scavenging factor in addition to being a cofactor of
      quinoprotein enzymes, and monoesters with the ester groups at C-2 of PQQ and C-9
      of IPQ are developed as treatment or preventive medicine for disease caused by
      radical compounds on the basis of strong radical scavenging activities,
      absorbability into cells, toxicity, safety and chemical stability.

PMID- 9151239
TI  - In vivo absorption of calcium carbonate and magnesium oxide from the large
      intestine in rats.
AB  - This study was conducted to evaluate the ability of the large intestine to absorb
      calcium (Ca) and magnesium (Mg) from their sparingly water-soluble salts, and
      also to determine whether fructooligosaccharides (FOS) stimulate the absorption
      of these minerals in rat large intestine in vivo. Rats were fed Ca- and Mg-free
      diets with and without 5% FOS. An aqueous suspension of CaCO3 and MgO was infused
      into the stomach via a gastric tube or into the cecum via an implanted catheter.
      Coprophagy was prevented by using wire-mesh anal cups throughout the experiment
      so as to exclude the re-ingestion of feces as an oral mineral source. In rats fed
      an FOS-free diet, the absorption degrees of Ca and Mg infused into the cecum were
      the same as those infused into the stomach. The absorption degree of phosphorus
      (P) was slightly but significantly higher in rats with the infusion of Ca and Mg
      into the cecum than in rats with the infusion of Ca and Mg into the stomach. FOS
      feeding increased the absorption of Mg to a similar extent in either case of
      infusion via cecal and oral routes, while FOS-feeding did not increase the
      absorption of Ca in rats with infusion of Ca and Mg into the cecum. We concluded
      that both CaCO3 and MgO are absorbed in the large intestine, and we ascertained
      that the increasing effect of FOS on the absorption of Mg took place mainly in
      the large intestine.

PMID- 9151240
TI  - Lipoprotein and apoprotein profiles of hyperlipidemic atherosclerosis-prone
      Japanese quail.
AB  - The purpose of this study was to characterize the lipoprotein and apoprotein
      profiles of hyperlipidemic atherosclerosis-prone (HAP) Japanese quail. HAP and
      commercially available (CA) Japanese quail were fed either a semi-purified diet
      containing 1% cholesterol or a cholesterol-free diet for two weeks. The
      lipoproteins of CA and HAP quail fed cholesterol-free diet were composed of two
      fractions: densities ranging from 1.02 to 1.09 and from 1.09 to 1.21. The
      lipoprotein distribution patterns obtained from both strains showed an HDL
      predominant pattern. A protein of 26 kDa was the major apoprotein in the entire
      density range of the lipoprotein class. Marked increases in the cholesterol ester
      levels were observed in the lower density fractions (1.006 < d < 1.055:
      chylomicron and VLDL fractions) of the cholesterol-fed quail, accounting for 46%
      of the total lipids in CA quail and 54% in HAP quail. In addition, the presence
      of a protein of 470 kDa was exclusively observed in the lower density fractions
      (1.006 < d < 1.055) of the cholesterol-fed HAP quail. The fatty-acid compositions
      of the chylomicron and VLDL fractions were affected by the dietary cholesterol in
      both strains: a decrease in concentration of 16: 0 and increase in 18: 0 (weight
      %). However, cholesterol feeding had no effect on the level of cholesterol,
      chemical composition or fatty-acid composition of the HDL fractions in either
      strain. Although the lipoprotein and apoprotein profiles of HAP quail showed
      resemblances to those of the CA quail, expression of the 470 kDa protein in the
      lipoproteins (d < 1.055) appeared to be pronounced in HAP quail. The relevance of
      these lipoprotein and apoprotein profiles to the genesis of atherosclerosis was
      discussed in this study.

PMID- 9151241
TI  - Japanese dietary protein allowance is sufficient for moderate physical exercise
      in young men.
AB  - The sufficiency of the dietary protein allowances recommended by the Ministry of
      Health and Welfare of Japan for various physical exercises has not been examined.
      We investigated the protein requirement for moderate-intensity physical exercise
      using nitrogen balance in the isoenergetic state. Seventeen healthy college
      students exercised for 10 days with an adaptation period of three days and non
      exercise control period of 10 days. They were given a maintenance level of energy
      and 1.08 g/kg per day of high quality mixed proteins recommended by the Ministry
      of Health and Welfare of Japan throughout the experimental period. They performed
      treadmill running during the exercise period at about 65% of VO2max for 25, 41 or
      48 min/day, which required 200, 300 or 400 kcal of extra energy, respectively.
      Although the exercise increased dermal nitrogen loss, urinary nitrogen excretion
      tended to decrease. Consequently, the exercise ranging from 200 to 400 kcal/day
      did not significantly alter the nitrogen balance. Thiobarbituric acid-reactive
      substances and glutathione disulfide were not increased after exercise,
      suggesting that the moderate exercise, recommended for health promotion by the
      Ministry of Health and Welfare of Japan, does not cause oxidative damage to
      healthy subjects. These findings demonstrate that a protein intake of 1.08 g/kg
      per day is enough for moderate exercise.

PMID- 9151242
TI  - Nutritional status of centenarians assessed by activity and anthropometric,
      hematological and biochemical characteristics.
AB  - For the maintenance of good health of very old people such as centenarians,
      nutrition is very important. However, the information on their nutritional status
      is very limited. In this study, we evaluated the nutritional status of
      centenarians by comparison with elderly in their 70 s and young adults. Volunteer
      subjects were comprised of 71 centenarians (51 females, 20 males) who were not
      bed ridden, 84 elderly in their 70 s (51 females, 33 males) who had no specific
      health problems and 27 healthy young adults in their 20 s (17 females, 10 males).
      We compared 11 items of the activities of daily living (ADL), height, weight,
      hematological (hemoglobin, hematocrit and red blood cell count) and biochemical
      [total protein, albumin, total-, HDL-, LDL- and VLDL-cholesterols, triglycerides,
      glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT)
      and creatinine] variables among the three age groups. Since the atrophy of muscle
      is more severe than the atrophies of other tissues in the elderly, we studied the
      muscle protein breakdown using plasma 3-methylhistidine (3-MH) as a marker. The
      results of all indices except serum lipids, GOT and GPT, were lower in the
      centenarians than in the subjects in their 20 s (p < 0.05) and were lower than
      the lower reference limits. Most of the results of the elderly in their 70s were
      within the reference intervals. However, as compared to the young subjects, they
      had: 1) normal ADL; 2) shorter height; 3) heavier weight in females and lighter
      weight in males; 4) lower total protein and albumin levels and albumin/globulin
      (A/G) ratios; and 5) higher total- and LDL-cholesterol levels in females and HDL
      cholesterol levels in males (p < 0.05). The plasma 3-MH concentration was higher
      in the centenarian group than in the young and elderly groups (p < 0.05).
      However, serum creatinine concentrations also tended to be high in the group,
      suggesting that a high 3-MH concentration did not indicate accelerated muscle
      protein breakdown but rather poor kidney functions. The results of this study
      show that the centenarians had shrunken stature, low hematological values and
      poor protein nutrition but rather normal lipid nutrition, however the elderly
      subjects in their 70s could still maintain most nutritional parameters in
      relatively normal condition.

PMID- 9151243
TI  - Dietary lipids and incidence of cerebral infarction in a Japanese rural
      community.
AB  - OBJECTIVE: To assess the relationship between dietary lipids and incidence of
      cerebral infarction in a Japanese rural population. DESIGN: A cohort study from
      July 1977 through December 1992. SETTING: Akadani-Ijimino (A-I) district, Niigata
      Prefecture, Japan. SUBJECTS AND METHODS: All the residents, 1,182 men and 1,469
      women, aged 40 years and over. Out of these members, 954 men and 1,329 women who
      were initially free of stroke completed a semiquantitative food frequency
      questionnaire in 1977, and were then subjected to a follow-up for 15.5 years. The
      occurrence of stroke was determined by the annual follow-up examination and
      registry. Dietary lipid was adjusted for total energy or fat intake by the
      residual method. Sex- and age-stratified and blood pressure- and atrial
      fibrillation-adjusted relative risk for cerebral infarction was estimated by the
      Cox proportional hazard model. RESULTS: There were 75 new cases of cerebral
      infarction during the observation period. The relative risk for cerebral
      infarction was less than one in the highest quartile level of total fat,
      saturated fatty acids (S), Keys score and westernized dietary pattern: 0.68-0.94.
      It ranged between 1.36 and 1.57 in the highest level of polyunsaturated (P), n-3
      and n-6 fatty acids, and P/S ratio. CONCLUSION: This study suggests the
      possibility that the traditional Japanese diet, very low fat intake, was likely
      to increase the risk of stroke through the low level of serum cholesterol as an
      intermediary factor.

PMID- 9151244
TI  - Endogenous factors responsible for the textural characteristics of buckwheat
      products.
AB  - Endogenous factors responsible for the textural characteristics of buckwheat
      products were studied. An analysis with various buckwheat samples showed that
      there were variations in protein, starch, amylose and amylopectin contents among
      the various buckwheat flours examined. The protein contents of the buckwheat
      flours were significantly negatively-correlated to the starch, amylose and
      amylopectin contents of buckwheat. A texturometric analysis showed that the
      springiness of heated-dough made from buckwheat flour was positively correlated
      to its starch content and amylopectin content, and the springiness and chewiness
      was negatively correlated to the protein content. Experiments adding isolated
      buckwheat protein or starch to buckwheat dough confirmed the above-mentioned
      correlation between texture and components. This study suggests that both the
      protein and starch present in buckwheat flour may be important factors
      responsible for the textural characteristics of buckwheat products.

PMID- 9151245
TI  - Long-term feeding of high vitamin E diet improves the decreased mitogen response
      of rat splenic lymphocytes with aging.
AB  - This study was performed to investigate whether the long-term feeding of a high
      vitamin E (VE) diet has a beneficial effect on the decreased cellular immune
      functions caused by aging. Male Fisher rats, 12 weeks old, were fed a regular (50
      mg VE/kg diet) or high VE diet (585 mg VE/kg diet) for 12 months. Then, the rats
      were sacrificed under anesthesia and their cellular immune functions were
      measured. The proliferation of splenic lymphocytes with PHA or Con A was
      significantly lower in old rats fed the regular diet as compared to that of young
      rats (two months old). In contrast, the proliferation of splenic lymphocytes in
      old rats fed the high VE diet was similar to that of young rats. The in vitro
      effect of macrophages (M phi) on the proliferation of splenic lymphocytes from
      young rats was investigated under Con A stimulation. Although splenic M phi
      isolated from old rats fed the regular diet did not have any effect on the
      proliferation of splenic lymphocytes, M phi from old rats fed the high VE diet
      significantly enhanced the proliferation of splenic lymphocytes. The
      responsiveness of splenic lymphocytes isolated from each group to the M phi of
      young rats under Con A stimulation was not significantly different between the
      young rats and old rats fed the regular diet. In old rats fed the high VE diet,
      the responsiveness of splenic lymphocytes to young rat M phi was significantly
      higher than that of the young rats or old rats fed the regular diet. Furthermore,
      the high VE diet induced a significant increase in interleukin 2 (IL2) production
      from splenocytes in both young rats and old rats following in vitro stimulation
      with Con A for 48 h. These results suggest that VE has the ability to improve the
      decreased cellular immune functions caused by aging, and appears to be associated
      with the enhancement of both M phi functions and lymphocyte responsiveness.

PMID- 9151246
TI  - Effects of lactitol-oligosaccharides on calcium and magnesium absorption in rats.
AB  - Lactitol-oligosaccharide (LO) was prepared from lactitol by transglycosylation
      reaction with Aspergillus oryzae beta-galactosidase. LO is resistant to
      metabolism in the small intestine but not in the large intestine. The effects of
      LO, lactose (Lac), lactitol (Lacol) and galactooligosaccharide (GL) on calcium
      and magnesium absorption were determined by feeding 8-week-old Sprague-Dawley
      male rats diets containing 5% of the above carbohydrates for two weeks. The
      results obtained were as follows. 1) A significant increase of calcium absorption
      was observed in the LO diet. 2) A significant increase of magnesium absorption
      was observed in the LO, GL and Lacol diets. 3) The concentration of total
      volatile fatty acids (VFA) in the cecal contents increased significantly in the
      LO, GL and Lacol diets. The main constituent of VFA in the cecal contents was
      found to be acetic acid. 4) The correlations between calcium and magnesium
      absorption ratios and total VFA concentration in the cecum were found to be
      significantly related. These findings suggest that LO is metabolized to VFA,
      among which acetic acid concentration seems to have the most stimulatory effect
      on the absorption of calcium.

PMID- 9151248
TI  - Antioxidative activity of barley hordein and its loss by deamidation.
AB  - Barley hordein was comparable to maize zein in antioxidation under a powder model
      system. Various deamidated "hordein" preparations were obtained and examined for
      their molecular-size distribution (by Sephacryl S-100 gel filtration),
      hydrophobicity (by fluorescence measurement using fluorescent probes) and
      antioxidative activity (by the ferric thiocyanate method). Deamidation caused
      fragmentation of the hordein molecule and simultaneously lowered its fatty acid
      binding capacity rather than its surface hydrophobicity. Then, the antioxidative
      activity diminished with increasing deamidation. When the fatty acid-binding
      capacity was plotted against the antioxidative activity, a high correlation (r2 =
      0.92) was observed between these two events.

PMID- 9151247
TI  - Menaquinone-4 accumulation in various tissues after an oral administration of
      phylloquinone in Wistar rats.
AB  - The distributions of phylloquinone (PK) and menaquinone-4 (MK-4) in various
      tissues were assessed after the oral administration of phylloquinone. Wistar rats
      were fed a vitamin-K-deficient diet for nine days, fasted for 24 h and then given
      phylloquinone orally at 4 mg/kg body weight. Rats were sacrificed 0, 6, 12 and 24
      h after the administration, and an analysis was made of the vitamin K analogues
      in the plasma, liver, brain, testis, kidney and spleen. The phylloquinone
      concentration in plasma and the tissues reached a peak 6 h after the oral
      administration of phylloquinone. By contrast, the concentration of MK-4 peaked in
      the liver, plasma, kidney and spleen at 12 h, and in brain and testis at 24 h.
      This data suggests that the ingested phylloquinone was probably converted into MK
      4 within the tissues themselves, rather than via hepatic metabolism. The evidence
      for this is that, after phylloquinone administration, (i) in each of the tissues,
      the MK-4 concentration increased much more slowly than that of phylloquinone, and
      (ii) the MK-4 concentration in the plasma and liver reached only much lower
      levels than those seen in other tissues.

PMID- 9151249
TI  - High-fat sunflower and olive oil diets affect serum lipid levels in steatotic rat
      liver differently.
AB  - This work describes the long-term effects of two different diets, one rich in
      olive oil and the other in sunflower oil, on serum lipid and lipoprotein levels
      after the establishment of fatty liver in rats 8 and 15 months old. The serum
      lipid and lipoprotein levels as well as the steatotic process have been evaluated
      by biochemical and histological methods, respectively. The results showed that
      fatty liver was well developed with both long-term high-fat diets, and
      hepatocytes were filled with many lipid droplets. This process was more evident
      in the portal zones, where fat hepatocytes were more numerous. Serum total
      cholesterol (TC) and HDL-C levels were highest in the sunflower oil fed rats,
      whereas the TG and LDL-C levels were highest in the olive oil group. Finally, the
      atherogenic indexes (HDL/TC, HDL/LDL, HDL/(TC-HDL)) were higher in the sunflower
      oil diet group than in the olive oil group.

PMID- 9151250
TI  - Supplementation of methionine to a low soybean protein diet strikingly increases
      pancreatic amylase activity in rats.
AB  - Feed efficiency in rats fed a low soybean protein isolate (SPI) diet (100 g/kg
      diet) was dramatically improved with the supplementation of L-methionine (3 g/kg
      diet). Pancreatic amylase activity was low in rats fed a low SPI diet, and was
      much higher in the supplemented group than in the non-supplemented group.
      Pancreatic trypsinogen and chymotrypsinogen contents (as activities of trypsin
      and chymotrypsin) were not changed with the methionine supplementation. In the
      small intestine, sucrase and leucine aminopeptidase in the jejunum and ileum were
      not clearly changed. In conclusion, a small amount of methionine supplemented to
      a low SPI diet especially induced pancreatic amylase among digestive enzymes. The
      factor involved in nutritional status, not the physiological action of methionine
      itself, may contribute the induction of amylase.

PMID- 9151251
TI  - Hydrolytic conditions for the formation of open-chain oligopeptides from
      cyclosporin A.

PMID- 9151252
TI  - L-Ala-substituted rat galanin analogs distinguish between hypothalamic and
      jejunal galanin receptor subtypes.
AB  - In order to explore which amino acids or which blocks of amino acids in the 29
      amino acid neuropeptide galanin are important for recognition of the endogenous
      ligand by galanin receptor subtypes present in the jejunum and in the
      hypothalamus, respectively, we have carried out L-Ala substitutions of individual
      amino acids or of blocks of amino acids in the rat galanin sequence and examined
      the binding of the obtained analogs to the rat hypothalamic and jejunal galanin
      receptor subtypes. This study reveals that the galanin sequence YLLGPH9-14 is
      essential for recognition of galanin by both the rat hypothalamic and jejunal
      galanin receptor subtypes. Substitution of the N-terminal amino acids. GWTL1-4,
      leads to total loss of affinity of galanin for both hypothalamic and jejunal
      galanin receptors. The alpha-helical C-terminal amino acid (25-29) part of
      galanin has no greater influence on the affinity of galanin to the hypothalamic
      galanin receptor subtype. L-Ala substitution of the C-terminal amino acids of
      galanin KHGLT25-29 shows, however, that this C-terminal motif is essential for
      the recognition by the jejunal galanin receptor subtype, whereas amino acids in
      the middle portion of galanin NSAG5-8 are of importance for binding to the
      hypothalamic but not to the jejunal receptor. [Ala5-8]Galanin thus has a more
      than 100-fold higher affinity to jejunal receptor than to the hypothalamic
      receptor, while [Ala25-29]galanin has a more than 100-fold higher affinity for
      the hypothalamic than for jejunal galanin receptor subtypes. pH dependence of the
      galanin binding to these receptor subtypes is also different.

PMID- 9151253
TI  - Conformations of cis- and trans-2,3-methanomethionine stereoisomers in the
      tripeptide mimic system Ac[cyclo-M]NHiPr.
AB  - Quenched molecular dynamics (QMD) was used to simulate low-energy conformers of
      the tripeptide mimics Ac?cyclo-Met?NHiPr, where the 2.3-methanomethionine is the
      cis-derivative (2R,3S)-cyclo-Met and the trans-derivative (2R,3R)-cyclo-Met.
      Variations of the favored omicron, upsilon values. and differences between the
      simulated preferred conformations for the two structures, were rationalized and
      discussed. Physical data for the cis-derivative (NMR, CD and FT-IR) gave no
      conclusive evidence for any preferred conformation. However for the trans
      derivative, Ac?(2R,3R)-cyclo-Met?NHiPr, the physical data suggests that a
      conformer with partial helical structure is favored. This work provides details
      of how the rigidly constrained side chain and cyclopropane of 2,3-methanoamino
      acids can be used to manipulate phi, psi values in a logical fashion.

PMID- 9151254
TI  - Solution structure of synthetic peptide inhibitor and substrate of cAMP-dependent
      protein kinase. A study by 2D H NMR and molecular dynamics.
AB  - Peptides derived from the inhibitor of cAMP-dependent protein kinase. PKI, have
      been studied by 2D 1H NMR techniques. These include the inhibitor PKI(6-22), the
      substrate [Ala20-Ser21]PKI(5-24), and a phosphorylated form of the latter [Ala20
      Ser21P]PKI(5-24). A homologous fold was found in the three peptides which
      consisted of an N-terminal segment in helical conformation to residue 13 and a C
      terminal segment poorly defined conformationally. A parallel study was carried
      out by molecular dynamics (MD) for the inhibitor peptide PKI(5-24). The N
      terminal helix, as observed in the crystal structure of the catalytic subunit
      PKI(5-24) complex, was conserved in the MD simulations with the enzyme-free
      inhibitor. Similarly the Gly14-Gly17 turn was apparent in all MD structures,
      whereas the C-terminal region, residues 18-24, was directed towards the N
      terminal helix in contrast to the extended conformation of this segment pointing
      away from the N-terminal helix in the crystal structure. This is primarily due to
      ionic interaction between Asp9 and Arg15. Indeed, a detailed analysis of the NOE
      contacts by NOESY at low temperature (2 degrees C) shows the occurrence of pH
      dependent contacts with Phe10. We conclude that the binding of short inhibitors,
      such as PKI(5-24), to the enzyme involves a conformational rearrangement of the C
      terminal region. The substrate [Ala20-Ser21]PKI(5-24) and the product [Ala20
      Ser21P]PKI(5-24), give very similar structures with local rearrangements
      involving some of the side chains.

PMID- 9151255
TI  - Chemical synthesis and characterization of the epidermal growth factor-like
      module of human complement protease C1r.
AB  - C1r is one of the two serine proteases of C1, the first component of complement,
      in which it is associated in a calcium-dependent manner to the homologous serine
      protease C1s. This interaction is mediated by the N-terminal region of C1r, which
      comprises a single epidermal growth factor (EGF)-like module containing the
      consensus sequence required for calcium binding, surrounded by two CUB modules.
      With a view to determine the structure of the EGF-like module of C1r and evaluate
      its contribution to calcium binding, this module [C1r(123-175)] was synthesized
      by automated solid-phase methodology using the Boc strategy. A first synthesis
      using the Boc-His(Z) derivative gave very low yield, due to partial deprotection
      of His residues leading to chain termination by acetylation, and to insertion of
      glycine residues. This could be circumvented by using the Boc-His(DNP) derivative
      and by condensation of appropriate glycine-containing segments. The synthetic
      peptide was efficiently folded under redox conditions to the species with three
      correct disulfide bridges, as determined by mass spectrometry and N-terminal
      sequence analyses of thermolytic fragments. The homogeneity of the synthetic
      peptide was assessed by reversed-phase HPLC and electrospray mass spectrometry.
      One-dimensional 1H NMR spectroscopic analysis provided evidence that the EGF-like
      module had a well defined structure, and was able to bind calcium with an
      apparent Kd of 10 mM. This value, comparable to that found for the isolated EGF
      like modules of coagulation factors IX and X, is much higher than that measured
      for native C1r. As already proposed for factors IX and X, it is suggested that
      neighbouring module(s), most probably the N-terminal CUB module, contribute(s) to
      the calcium binding site.

PMID- 9151256
TI  - Size-exclusion chromatography of protected synthetic polypeptide tandems in an
      organic solvent.
AB  - A novel method for analytical and preparative size exclusion chromatography of
      large water-insoluble protected peptides in an organic solvent was developed.
      This method was applied to analysis and separation of protected synthetic peptide
      tandem repeats and to a control of the reaction of peptide fragment coupling.
      Columns containing Toyopearl HW-40, HW-50; HW-55 and HW-60 gels of Fine grade
      were used, and the selectivity of each sorbent, as well as the chromatographic
      behaviour of the peptides on them, were examined. Separation ranges of these gels
      applied to separation of protected peptides in DMF were shown to be much smaller
      (ca. 400-14,000 Da) than those of the same gels applied to protein separations in
      water buffers (100-1,000,000 Da). An initial evaluation of efficiency of
      Toyopearl HW Superfine grade gels with respect to similar separations was
      performed.

PMID- 9151257
TI  - Synthesis and activity of partial retro-inverso analogs of the antimetastatic
      laminin-derived peptide, YIGSR-NH2.
AB  - This paper describes the synthesis and biological evaluation of six partial retro
      inverso peptidomimetic analogs of YIGSR-NH2, a synthetic peptide from the beta 1
      chain of laminin, which has antimetastatic activity. The intent was to improve
      the antimetastatic potency of YIGSR-NH2 by limiting the in vivo enzymatic
      degradation through the incorporation of fraudulent peptide bonds. We have
      prepared the following retro-inverso peptides, Tyr-Ile-Gly-Ser-gArg-CHO (1), Tyr
      gIle-mGly-Ser-Arg-NH2 (2), Tyr-gIle-mGly-Ser-gArg-CHO (3), gTyr-D-rIle-mGly-Ser
      Arg-NH2 (4), Tyr-Ile-Gly-gSer-D-rArg-CHO (5) and Tyr-gIle-rGly-D-rSer-D-rArg-CHO
      (6). In vitro assays for B16F10 melanoma cell adhesion showed no significant
      activity for these six peptides. Peptides 1-3, 5 and 6 were further tested, in
      vivo, for their ability to inhibit tumor metastases to the lung in mice injected
      in the tail vein with B16F10 melanoma cells. All five of the retro-inverso
      peptides tested showed statistically significant inhibition of metastasis, but
      the most active peptides were 5 and 6, which showed 57 and 69% inhibition of
      metastasis, respectively.

PMID- 9151258
TI  - Nuclear magnetic resonance studies of the C-terminal human growth hormone
      fragment I179-C182-[SS]-C189-P191 and the related trisulfide peptide I179-C182
      [SSS]-C189-P191.
AB  - The synthetic C-terminal hGH fragment I179-C182-[SS]-C189-P191 and the related
      trisulfide peptide I179-C182-[SSS]-C189-P191 have been studied using homonuclear
      1H-NMR methods and distance geometry calculations. The 1H-NMR spectra of both the
      disulfide (diS) and the trisulfide (triS) were completely assigned. Amide proton
      exchange rates, NOEs and the temperature dependence of the NH chemical shifts
      indicate a hydrogen bond in triS between Val185 and Ser188 stabilizing a turn in
      this region. 3JH,H coupling constants and NOEs were measured and used as input
      for distance geometry calculations. For triS two families of structures with
      averaged pairwise backbone root mean square deviations for Cys182-Cys189 of 1.3
      1.5 A were found, only one of which is compatible with experimental data. For diS
      only one family of structures was found, but with such a low structural
      definition (back bone rmsd > 2 A) that no interpretation into a consensus
      structure is useful. The generated structures were compared to the crystal
      structure of the terminal loop in hGH, complexed to its binding proteins. The
      resemblance was low between the solution structures of the tridecapeptides and
      the terminal hGH loop.

PMID- 9151259
TI  - Influence of L-naphthylalanine in position 3 of AVP and its analogues on their
      pharmacological properties.
AB  - We describe the synthesis and pharmacological properties of two series of
      analogues: one which consists of three peptides having L-1-naphthylalanine in
      position 3 and the second composed of analogues substituted in position 3 with L
      2-naphthylalanine. All peptides were tested in bioassays for pressor and
      antidiuretic activities. We also checked the uterotonic activity in vitro. We
      observed that the activity of counterparts in both series is, in two cases,
      strikingly different. One of the new analogues, [(L-2-Nal)3,(D-Arg)8]VP is among
      the most potent antagonists of the vasopressor response to AVP. Moreover, it is
      the first potent V1 antagonist devoid of antiuterotonic activity. This analogue
      was designed without modification of position 1, which was previously thought to
      be essential for substantial pressor antagonism. Two other peptides, [Mpa1;(L-2
      Nal)3;(D-Arg)8]VP and [Mpa1,(L-1-Nal)3,D-Arg)8]VP, are highly potent V2 agonists.
      The second analogue is highly selective. With the exception of [(L-2-Nal)3]AVP,
      which showed weak antioxytocic activity, (L-Nal)3 modification resulted in the
      almost complete removal of interaction of our analogues with oxytocic receptors
      in vitro. Our results suggest that position 3 in AVP and its analogues is
      important not only for binding and recognition as previously though, but also for
      pressor, antidiuretic and uterotonic activities. We also assume that the
      hindering effect caused by bulky naphthyl moiety has a significant impact on the
      bioactive conformations of molecules which contain Nal residue, and can thus
      influence their interaction with V1, V2 and oxytocic receptors.

PMID- 9151260
TI  - Salt-dependent conformational diversity of alternating poly (Glu-Leu).
AB  - Alternating poly(Glu-Leu) was synthesized by the condensation of the
      corresponding dipeptide p-nitrophenyl ester at high concentration. It exhibits a
      random coil structure in pure water at neutral pH. Addition of monovalent
      cations, such as NH4+ to a final 0.1 M solution, induces a transition to a water
      soluble beta-structure. The salt effect is quite selective since no transition
      was observed with Li+, Na+ or Cs+ ions. Addition of 0.5 equiv of calcium, cobalt
      or manganese chlorides per glutamyl residue induces similar coil to beta-sheet
      transitions. No polymer precipitation was observed at these very low salt
      concentrations. Addition of 0.5 equiv. of Cu2+ or 0.15 equiv. of Fe3- induces a
      coil to alpha-helix transition. Molecular modeling has been used to understand
      tentatively the main factors controlling the different conformations observed
      with the various metal ions.

PMID- 9151261
TI  - Use of Fmoc-N-(2-hydroxy-4-methoxybenzyl)amino acids in peptide synthesis.
AB  - The use of N,O-bisFmoc-N-(2-hydroxy-4-methoxybenzyl)amino acid derivatives in the
      synthesis of peptides with difficult sequences has already been described. With
      these amino acid derivatives the reversible protecting group 2-hydroxy-4
      methoxybenzyl (Hmb) for the backbone amide bonds of peptide chains is introduced,
      and thus the aggregation due to hydrogen-bond interchain association is
      inhibited. This paper describes the synthesis and use of Fmoc-N-(2-hydroxy-4
      methoxybenzyl)amino acid derivatives as an alternative means of introducing Hmb
      backbone protection. These new monoFmoc derivatives were obtained in higher yield
      than the bisFmoc derivatives. Coupling yields to the amino peptide resin were the
      same as those obtained with bisFmoc derivatives, under the TBTU HOBt/DIEA
      conditions. We also compared different syntheses of a difficult peptide with the
      Fmoc approach [triple coupling, capping, use of chaotropic agents, backbone
      protection using monoFmoc (Hmb)Ala] and with optimized Boc chemistry. Both the
      backbone protection and optimized Boc chemistry approaches gave the desired
      product in excellent yield and purity.

PMID- 9151262
TI  - Judson C. Hickey Scientific Writing Award Winner. A method of fabrication of a
      facial prosthesis that improves retention and durability: a clinical report.
AB  - This clinical report describes a technique for the fabrication of a facial
      prosthesis with a visible light-curing resin overlaid with a silicone elastomer.
      Clinical observations have revealed considerable improvement in the duration of
      retention of the prosthesis with an adhesive and enhanced longevity of the
      prosthesis as compared with conventional silicone elastomer facial prostheses
      retained with the same adhesive.

PMID- 9151263
TI  - Temporary prosthesis for laryngotracheal stenosis: a clinical report.
AB  - Clinical and laboratory procedures to fabricate a transitional prosthesis for
      patients treated with laryngofissure surgery have been described. Hard resin
      promoted healing of the surgical area and maintained the opening because of its
      stiffness. The prosthesis, which can be highly polished, was easily removed by
      the patient for proper hygiene and was fabricated to accurately fit the inside
      margins of the wound. All these factors were important for a good clinical
      result.

PMID- 9151264
TI  - Precision of in vivo colorimetric assessments of teeth.
AB  - PURPOSE: The repeatability of an intraoral positioning device for a tristimulus
      photoelectric colorimeter was assessed with the left maxillary central incisors
      of seven subjects. MATERIAL AND METHODS: Intraclass correlation coefficients and
      repeatability color differences were determined from repeated color measurements
      made by the same examiner on 3 separate days. Interexaminer repeatability was
      tested by comparing CIELAB measurements of the same tooth made by two different
      examiner combinations, both using the positioning device. RESULTS: High
      intraclass correlation coefficients were demonstrated for intraexaminer and
      interexaminer repeatability. Repeatability color differences were 0.34 delta E
      units for intraexaminer assessments, whereas interexaminer repeatability color
      differences were 0.13 and 0.61 delta E units for the two examiner pairs.
      CONCLUSIONS: It was concluded that a colorimeter, equipped with a custom
      positioning jig, had acceptable precision for intraoral measurement of
      longitudinal changes in tooth color.

PMID- 9151265
TI  - Effect of irradiation time on tensile properties of stiffness and strength of
      composites.
AB  - PURPOSE: We compared the effect of irradiation time on the diametral tensile
      strength and stiffness of three visible light-cured composites. The sensitivity
      of the two mechanical properties to differentiate between the materials was also
      investigated. MATERIAL AND METHODS: Cylindrical specimens of three composites
      were cured for 20, 40, 80, and 120 seconds (n = 10) and loaded up to failure in a
      diametral tensile strength test. Stiffness and diametral tensile strength values
      were recorded. RESULTS: Irradiation time significantly influenced diametral
      tensile strength (p = 0.0017) and stiffness (p = 0.0002). With the same
      irradiation times the three tested materials demonstrated no significant
      difference when diametral tensile strength was studied (p = 0.31). However,
      stiffness values did show a significant difference (p = 0.0002). CONCLUSIONS:
      This study found that stiffness is more sensitive in disclosing differences in
      tensile properties between the materials than diametral tensile strength.

PMID- 9151266
TI  - Effect of convergence angle on retention of resin-bonded retainers cemented with
      resinous cements.
AB  - STATEMENT OF PROBLEM: Poor retention is a common cause of failure for resin
      bonded restorations. PURPOSE: This study evaluated the effect of the convergence
      angle of tooth preparations on retention of resin-bonded restorations, luted with
      adhesive and conventional resinous cements. MATERIAL AND METHODS: A total of 80
      posterior retainers with four different tooth preparation angles were cemented
      with two different resinous cements, and retentive strength was measured.
      RESULTS: The results indicated that (1) increased tapering of tooth preparations
      resulted in loss of retention and this variable was statistically significant for
      both cements used when convergence angles exceeded 10 degrees and (2) sandblasted
      nickel-chromium retainers, combined with adhesive resins, should provide
      sufficient retention for posterior resin-bonded fixed partial dentures.

PMID- 9151267
TI  - Marginal fidelity of crowns fabricated from six proprietary provisional
      materials.
AB  - STATEMENT OF PROBLEM: The most important requirement for an interim crown is
      suitable marginal adaptation. PURPOSE: This in vitro study compared vertical
      discrepancies of margins for complete crowns made with six provisional materials
      (Provipont, Protemp Garant, Unifast LC, Triad VLC, Splintline, and Jet). MATERIAL
      AND METHODS: A direct technique was used to fabricate 60 provisional complete
      crowns on prepared molars with a polyvinyl siloxane impression and a vacuum
      formed polypropylene sheet as matrices. A measuring microscope was used to
      measure vertical marginal discrepancies at x 100. Data were analyzed with Kruskal
      Wallis one-way analysis of variance and Mann-Whitney U tests (alpha = 0.05).
      RESULTS: Significant differences were found between resinous materials tested (p
      = 0.0002) and multiple comparisons tests indicated no significant difference
      between Splintline and Protemp Garant; Provipont, Unifast LC, and Triad VLC; and
      Unifast LC, Triad and Jet provisional materials. CONCLUSIONS: This study
      indicated that provisional crowns fabricated with Splintline and Protemp Garant
      interim restorative materials recorded the least marginal discrepancies.

PMID- 9151268
TI  - In vivo color stability of resin-veneered telescopic dentures: a double blind
      pilot study.
AB  - STATEMENT OF PROBLEM: Discoloration is a major disadvantage of resin veneers on
      telescopic dentures. In vitro color measurements with large and flat samples of
      resin veneer composites have been published, but no in vivo data are available.
      PURPOSE: This study describes the discoloration of resin veneers in vivo by use
      of spectrophotometry and the L*a*b* system of the Commission Internationale de
      L'Eclairage (CIE). METHODS: In a clinical evaluation of this technique, two
      composite veneer materials were compared in 18 patients. RESULTS: Both brands
      discolored significantly after 1 year. While L* and a* were not changed
      significantly, b* and the total color difference delta E increased by
      approximately 2 units each year. No statistically significant differences were
      found between the materials.

PMID- 9151269
TI  - Tissue volume considerations in implant prosthodontics.
AB  - STATEMENT OF PROBLEM: The replacement of intraoral hard and soft tissue is
      dependent on careful dimensional consideration. The prosthetic phase of implant
      treatment frequently involves the restoration of significant amounts of hard and
      soft tissue in addition to teeth. Although similarities to both tooth-supported
      fixed prostheses and removable prostheses exist, implant-supported fixed
      prostheses engender unique problems with respect to prosthetic contours. PURPOSE:
      This article depicts diagnostic methods used to compare anticipated prosthesis
      volume with existing clinical conditions. The proper functional, esthetic, and
      biomechanical design of the definitive prosthesis will be shown to relate
      directly to understanding these dimensional requirements.

PMID- 9151270
TI  - The precision of fit at the implant prosthodontic interface.
AB  - STATEMENT OF PROBLEM: Percussion, visual observation, and conventional periapical
      radiographs are the methods most frequently used clinically to evaluate the
      accuracy of implant component assemblies, whereas methods to measure the
      precision of fit are limited. PURPOSE: In this study the Periotest instrument was
      used to evaluate the stability of the interfaces between the implant and the
      abutment, along with the abutment and the gold cylinder under a series of
      assembly conditions. The hypothesis tested is that a more negative Periotest
      value (PTV) would indicate an accurate fit and a more positive value PTV would
      correlate with an inaccurate fit. MATERIAL AND METHODS: To investigate this
      hypothesis in vitro, two bovine ribs were used as patient simulation models. Each
      model contained three self-tapping Branemark implants placed approximately 7 to
      10 mm apart and arranged in a reasonable curvature. A series of component
      assembly conditions were created as accurate and inaccurate with thickness gauges
      of 25.4 microns, 50.8 microns, and 101.6 microns. RESULTS: The mean Periotest
      values and SDs for accurately assembled abutments and gold cylinders were -6.0 +/
      0.32 and -3.4 +/- 0.68, respectively. Periotest value data of the assembly
      conditions were statistically analyzed with multiple regression analysis. The
      misfit in the implant to abutment interface resulted in a more negative Periotest
      value trend (r = 0.54) with increases in gauge thickness. However, the same
      magnitudes of misfit at the abutment to gold cylinder interface produced a more
      positive Periotest value trend (r = 0.72). CONCLUSION: The PTV trends were
      consistent with increased stability at the abutment to implant interface from the
      increasing magnitude of misfit created with the thickness gauges. In contrast,
      the measurement trends observed for the abutment to gold cylinder interface were
      consistent with decreased stability with each increase in gauge thickness
      inserted at the interface.

PMID- 9151271
TI  - Construction of a clinical implant performance scale for implant systems with
      overdentures with the Delphi method.
AB  - STATEMENT OF PROBLEM: The success of an implant system is often judged on the
      survival rate of the separate implants. This does not give a complete view of the
      "real" success of a system. To make that possible the total clinical performance,
      surgical and prosthetic, has to be considered. PURPOSE: This study aimed to set
      up a clinical performance scale for different implant systems retaining
      mandibular overdentures. MATERIAL AND METHODS: All data regarding surgical and
      prosthetic complications incurred and treatment procedures needed after implant
      placement were collected from a group of 90 patients who were treated either with
      two root form implants connected with a bar and supporting a mandibular
      overdenture or with a transmandibular implant system that supported an
      overdenture. All items were scored into five categories on the scale, defined as
      the "clinical implant performance" scale. The Delphi method was applied to
      categorize each item. A panel of experts assessed the items. RESULTS: After three
      rounds there was complete consensus between the experts for 65% of the items for
      the root form implant systems, and for 87% of the items at least five out of six
      experts gave the same score. For 55% of the items for the transmandibular
      implants systems there was complete consensus, and for 85% of the items at least
      five out of six experts scored in the same way. CONCLUSIONS: The Delphi method
      provides a useful scale for evaluating the clinical performance of implant
      systems retaining mandibular overdentures. The presented scale makes it possible
      to compare the overall performance of different implant systems for overdentures.

PMID- 9151272
TI  - Management of temporomandibular disorders: concepts and controversies.
AB  - STATEMENT OF PROBLEM: Controversy continues in the area of epidemiology,
      etiology, diagnosis, and management of temporomandibular disorders (TMD). The
      field is replete with testimonials and clinical opinion, but it has been lacking
      in scientific foundation. PURPOSE: This article reviews the recent
      temporomandibular disorder and orofacial pain literature and summarizes the
      concepts published in the 1993 and 1996 American Academy of Orofacial Pain
      guidelines. Temporomandibular disorders rarely occur as single entities but
      rather as multiple problems with overlapping symptoms. CLINICAL SIGNIFICANCE: The
      multicausal nature of these problems and the number of conditions with similar
      signs and symptoms demand an effective differential diagnostic process.
      Diagnostic criteria are used from an operational standpoint to establish specific
      diagnoses based on a multiaxial diagnostic model. CONCLUSION: Because little is
      known about the natural course of the various classifications of
      temporomandibular disorders, and because most treatment approaches are reported
      to be equally effective, a conservative, noninvasive management program is
      endorsed. The emphasis is on a medical multidisciplinary model similar to ones
      used for other musculoskeletal disorders that involve the patient in the physical
      and behavioral management of his or her own problem. This article concludes that
      a majority of temporomandibular disorder patients achieve good relief of symptoms
      with noninvasive reversible therapy.

PMID- 9151273
TI  - Evaluation of wear: enamel opposing three ceramic materials and a gold alloy.
AB  - STATEMENT OF PROBLEM: The wear of human enamel and of the restorative material is
      often a critical concern when selecting a restorative material for any given
      clinical restorative treatment. PURPOSE: This in vitro wear investigation
      evaluated three ceramic restorative materials and one type III gold (the control)
      opposing enamel. MATERIAL AND METHODS: The area of enamel lost at specified time
      intervals, the stylus area lost, and the combined stylus and enamel vertical
      height lost were evaluated. RESULTS: Enamel wear opposing one type III gold was
      statistically similar to that of Dicor MGC, which was lower than that of Vita
      Mark II and IPS Empress, which were also statistically similar in value.
      CONCLUSIONS: The total vertical height lost from the type III gold specimens and
      opposing enamel was statistically lower than that of Dicor MGC and IPS Empress
      (alpha < 0.05).

PMID- 9151275
TI  - Retention of Candida albicans on acrylic resin and silicone of different surface
      topography.
AB  - STATEMENT OF PROBLEM: The adhesion of microorganisms to a denture surface is a
      prerequisite for colonization. PURPOSE: This study compared the retention of
      Candida albicans on smooth and rough acrylic resin and silicone surfaces after a
      washing procedure to determine the effect of surface roughness on prosthesis
      infection and hygiene. MATERIAL AND METHODS: Standardized cell suspensions of C.
      albicans were incubated with smooth and rough acrylic resin and silicone surfaces
      for 1 hour at 24 degrees C. After washing, cells that had been retained on the
      surface were stained with acridine orange and examined with incident beam
      fluorescent microscopy. RESULTS: There was no significant difference in cell
      numbers on either of the smooth surfaces. Significantly higher numbers of cells
      (p > 0.0005) were observed on roughened surfaces (silicone > acrylic resin) than
      on smooth surfaces. The fitting surface of the maxillary denture was not
      polished. CONCLUSIONS: Silicones used in prostheses were processed against dental
      stone. The resultant surface roughness may facilitate microbial retention and
      infection and should therefore be kept to a minimum.

PMID- 9151274
TI  - Water sorption and solubility of glass fiber-reinforced denture polymethyl
      methacrylate resin.
AB  - Polymethyl methacrylate (PMMA) absorbs water slowly over a period of time,
      primarily because of the polar properties of the resin molecules. The aim of this
      study was to determine the water sorption and solubility of heat-cured and
      chemical-cured glass fiber (GF) PMMA composite used in dentures. The test
      specimens (n = 5) were fabricated from experimental, unidirectional, continuous
      GF reinforcement; the GF concentration of the test specimens was approximately
      11% by weight. Water sorption and solubility were tested in accordance with
      International Standards Organization specification No. 1567. The results revealed
      that the type of acrylate had more of an effect on water sorption than did the
      presence of GF reinforcement in the test specimen (p = 0.001 and p = 0.049,
      respectively). In the GF-reinforced test specimens the type of PMMA also affected
      the water sorption values (p = 0.006). GF reinforcement affected the solubility
      values of the test specimen (p = 0.002), but the type of acrylate had no effect
      on solubility (p = 0.585). The results of this study suggest that the water
      sorption and solubility of unreinforced PMMA and PMMA reinforced with GF are in
      accordance with International Standards Organization specification No. 1567.

PMID- 9151277
TI  - A procedure for a modified cylindric titanium abutment.
AB  - In the restoration of a single anterior edentulous space with a dental implant,
      there are three transmucosal elements that could be used within the Nobel Biocare
      system: the CeraOne abutment, the Estheticone abutment with a nonrotating gold
      cylinder, and the CerAdapt abutment. This article describes a procedure to modify
      the CeraOne cylindric titanium abutment with titanium ceramics to achieve an
      anatomically shaped transmucosal element that does not show evidence of the metal
      through thin gingival tissue.

PMID- 9151276
TI  - Crown foundations with a custom matrix, composites, and reverse carving.
AB  - This article describes a restorative technique for the formation of composite
      cores for artificial crowns. The procedure uses a semirigid matrix with reverse
      carving to form the cores on substantially compromised teeth. The matrix allows
      the placement of the composite under pressure to reduce voids and gaps and
      permits completion of multiple cores simultaneously. Reverse carving enables
      development of a common axis for multiple cores. The dentist can perform the
      tooth preparation for the crown at the time of the core restoration. The effort
      commonly applied to developing tooth morphologic features in the core can be
      invested instead in the formation of the interim restoration. The remaining tooth
      structure, pin or post placement, and location of the finish line can be
      evaluated with the insight of a crown foundation and not merely as a traditional
      restoration.

PMID- 9151278
TI  - Facial approach to stabilization of mobile maxillary anterior teeth with steep
      vertical overlap and occlusal trauma.
AB  - The necessity for splinting and the advantages of some types of permanent,
      semipermanent, and temporary splinting are given. Specific step-by-step
      instructions are given for a special purpose splint that can be used for
      stabilizing mobile maxillary teeth when the patient has thin teeth faciolingually
      and a steep vertical overlap. This can be the treatment of choice for such
      patients.

PMID- 9151279
TI  - Pattern waxes and inaccuracies in fixed and removable partial denture castings.
AB  - It is the desire of every dentist and dental technician to produce a restoration
      that will fit the patient with a minimum of adjustments and certainly one that
      does not require remaking. Yet many abuse the materials with which they work,
      either through improper manipulation, lack of familiarity with their properties,
      or by attempting to reduce laboratory time by taking short cuts. Wax is one of
      the materials that requires more knowledge and skill to manipulate accurately
      because it has a considerably higher coefficient of thermal expansion (and
      contraction) than any other dental material. It often contributes considerably to
      the inaccuracies of cast dental restorations. This article provides a review of
      dental waxes used to make prosthodontic castings and points out some of the
      properties of waxes that must be controlled to make accurate restorations.

PMID- 9151281
TI  - Tissue stops aid in improving accuracy of impressions.

PMID- 9151280
TI  - Improving marginal adaptation for type III gold castings.

PMID- 9151282
TI  - Development of a screening method for anti-6 beta-hydroxycortisol antibody using
      an enzyme-linked immunosorbent assay (ELISA) and its applications.
AB  - An indirect enzyme-linked immunosorbent assay (ELISA) for the detection of anti-6
      beta-hydroxycortisol (6 beta-OHC) antibody has been developed. After immunization
      of 6 beta-OHC protein conjugates in New Zealand White rabbits, specific
      polyclonal antibody to 6 beta-OHC was detected by ELISA in which the wells of
      microtiter plates were coated with 6 beta-OHC conjugated to protein. The rabbit
      anti-6 beta-OHC antibody titer was above 1:500,000 dilution. Cross-reactivity
      with other structurally related steroids such as cortisol hydrocortisone was less
      than 5%. The sensitivity of the polyclonal antibody was comparable to previous
      studies reported, and was within the accepted detection limit for 6 beta-OHC in
      man and in laboratory animals. The assay has a low detection limit of 1 ng/ml, an
      intraassay variation of 3.1% and an interassay variation of 5.2%. The application
      of the anti-6 beta-OHC-based-ELISA to detect urinary 6 beta-OHC was tested by
      measuring the concentration of 6 beta-OHC in man before and after enzyme
      induction by rifampicin treatment. The mean 24 h urine output of 6 beta-OHC in
      man subjects was 370 +/- 105 micrograms and 1350 +/- 201 micrograms before and
      after rifampicin administration, respectively. This polyclonal anti-6 beta-OHC
      antibody-based ELISA can be modified to detect mouse anti-6 beta-OHC IgG with
      equally good precision and specificity which should be useful in screening
      positive clones of a 6 beta-OHC IgG secreting mouse hybridoma currently being
      developed for detecting enzyme induction of CYP3A4 in man and laboratory animals.

PMID- 9151283
TI  - A general method for DNA polymorphism identification in genetic assessment and
      molecular diagnosis.
AB  - A general methodology for the analysis of human diseases at the nucleic acid
      level has been described. This method consists of a semiautomated, nontoxic
      analytic procedure, staining DNA bands with silver nitrate instead of ethidium
      bromide after DNA amplification by PCR. This technique provides a sensitive assay
      with enhanced accuracy and offers the possibility of carrying out the molecular
      analysis of several polymorphisms in a single day simplifying molecular genetics
      with diagnostic purposes.

PMID- 9151284
TI  - Effects of verapamil on electroconvulsive shock- and clonidine-induced amnesia.
AB  - The effect of the Ca2+ blocker verapamil on amnesia induced by electroconvulsive
      shock (ECS) or by the alpha-adrenoceptor agonist clonidine was studied in male
      Wistar rats trained in passive avoidance task ("step down"). Clonidine (0.1
      mg/kg, i.p.) and ECS induced a pronounced amnesia, significantly reducing the
      percentage of rats that had acquired the task upon retention tests, given 3 h, 24
      h and 7 days after training. Verapamil (10 mg/kg) administered orally for 12 days
      (5 days before and 7 days after training) completely abolished the ECS- or
      clonidine-induced amnesia. These data suggest that calcium channel blocker
      verapamil has a protective effect against experimentally provoked memory deficit
      and might be useful for the treatment of cognitive disorders.

PMID- 9151285
TI  - Effects of anapsos on the activity of the enzyme Cu-Zn-superoxide dismutase in an
      animal model of neuronal degeneration.
AB  - The enzyme Cu-Zn-SOD is a metalloenzyme that catalyzes the dismutation of the
      superoxide radical into hydrogen peroxide and molecular oxygen, being a defense
      system against free radical formation. Free radical reactions are implicated in a
      variety of physiological and pathological processes as aging, apoptosis and
      neurodegenerative diseases, and abnormalities associated with SOD have been
      recently documented in several neurodegenerative processes. In this study, we
      have evaluated the effect of anapsos on Cu-Zn-SOD activity in rats with
      injections of beta-amyloid protein or water bilaterally into the hippocampus.
      These injections caused severe cell depletion in the gyrus dentatus. Anapsos is a
      biological extract obtained from the fern Polypodium leucotomos with
      immunomodulatory and anti-neoplastic effects tested in animals and humans. Cu-Zn
      SOD activity was measured in the hypothalamus, hippocampus, cerebral cortex,
      liver and spleen of rats treated i.p. with three doses of anapsos for 7 days (4,
      20 and 100 mg/kg/day). Control animals were treated with saline solution under
      the same conditions. Anapsos significantly modified enzyme activity in all the
      areas tested. Lower doses of anapsos produced decreased SOD activity in the
      hypothalamus, hippocampus, liver and spleen, while in the cerebral cortex, a
      significant dose-dependent increase in SOD activity was observed. These results
      indicate that anapos was able to modify Cu-Zn-SOD activity in this animal model
      of neuronal degeneration, which may indicate the participation of anapsos in
      mechanisms of tissue repair after brain damage.

PMID- 9151287
TI  - Vascular chemical sulfhydryl alkylation in vitro: alterations in intracellular
      calcium and cAMP and cGMP metabolism.
AB  - This study examined the effect of N-ethylmaleimide (NEM, 10(-7) M) on agonist
      induced contraction and the relaxation following drug-washout, of vascular smooth
      muscle (VSM) segments derived from hypertensive rabbits. Mean blood pressure
      increase was produced either by renal constriction plus contralateral
      nephrectomy, or by cadmium acetate ingestion. Freely-ionized calcium (45Ca)flux,
      cyclic 3':5'-guanosine monophosphate (cGMP), and cyclic 3':5' adenosine
      monophosphate (cAMP), were analyzed. NEM was used as a stereoselective probe to
      clarify the role of sulfhydryl (SH) groups in hypertension. Contractile response
      to norepinephrine (NE, 5.9 x 10(-7) M), angiotensin II (AT, 9.8 x 10(-8) M), and
      potassium chloride (KCl, 2.2 x 10(-2) M) were significantly depressed in
      hypertensive tissue. Exposure to NEM, before agonist challenge, caused an even
      greater depression in contractile response. As for the normotensive group, an
      inhibition of relaxation occurred when NEM was added after the development of a
      maximal contractile response to NE, AT or KCl. Changes in contractile ability and
      in relaxation were attributed to specific alterations in calcium distribution.
      These alterations were examined by 45Ca washout components and were related to
      cAMP and cGMP metabolism. These results suggest a regulatory role of SH groups in
      contraction and relaxation and a modification of this role in hypertension.

PMID- 9151286
TI  - Antianxiety profile of ondansetron, a selective 5-HT3 antagonist, in a novel
      animal model.
AB  - The profile of action of ondansetron was assessed in a novel animal model of
      anxiety. The mirrored chamber is a nonpunishing quantitative model of anxiety
      which measures approach-conflict behavior. Ondansetron in all the doses tested
      (0.01, 0.1 and 1 mg/kg i.p.) showed significant anxiolytic action as compared to
      naive mice, but it was less potent as compared to a well-known anxiolytic,
      diazepam (1 mg/kg). These results suggest that ondansetron has anxiolytic
      efficacy in nonconflict paradigms of anxiety, a response not mediated by the
      conventional neurotransmitter receptors. GABA-benzodiazepine as flumazenil (4
      mg/kg), a benzodiazepine receptor antagonist, failed to reverse the behavioral
      parameters evoked by ondansetron.

PMID- 9151288
TI  - Effect of angiotensin-converting enzyme inhibition on Na+/H(+)-exchange and
      Ca(2+)-efflux in human erythrocytes.
AB  - The effect of the angiotensin-converting enzyme inhibitor, captopril, on Na+/H(+)
      exchange activity and on Ca(2+)-ATPase mediated Ca(2+)-efflux was investigated in
      red blood cell membranes of patients with essential hypertension. The erythrocyte
      Na+/H(+)-exchange rate was measured as the difference in H(+)-efflux rate when
      measured in the presence or absence of Na+. The erythrocyte Ca(2+)-transport
      mediated by Ca(2+)-ATPase was assayed as the erythrocyte Ca(2+)-efflux rate. Our
      data show that captopril, in vitro and in vivo, inhibits the Ca(2+)-ATPase
      mediated Ca(2+)-efflux rate in human erythrocytes, while in vivo it stimulates
      the erythrocytes Na+/H(+)-exchange rate.

PMID- 9151289
TI  - Abnormalities in the metabolism of acetaminophen in patients infected with the
      human immunodeficiency virus (HIV).
AB  - The urinary concentration of acetaminophen and its glucuronide, sulphate,
      cysteine, and mercapturate conjugates was measured by high-performance liquid
      chromatography in 32 healthy volunteers, 9 untreated symptom-free HIV
      seropositive subjects, and 19 patients with AIDS after a single oral dose of 1.5
      g of acetaminophen. The concentration of the glucuronide conjugate was
      significantly lower in AIDS patients when simultaneously compared with
      concentrations found in healthy individuals and symptoms-free HIV-seropositive
      subjects. Differences between healthy volunteers and symptom-free HIV
      seropositives were not encountered. By contrast, urinary concentrations of
      sulphate and oxidation pathway-derived metabolites were significantly higher in
      AIDS patients as compared with the other two groups. When AIDS patients treated
      with zidovudine were compared with those not given this medication, differences
      in the urinary excretion of acetaminophen and its metabolites were not observed.
      However, the urinary concentration of mercapturic acid was significantly higher
      in those given enzyme inducers, such as rifampicin or phenytoin, than in AIDS
      patients not treated with these drugs. In summary, patients with advanced HIV
      infection showed reduced acetaminophen glucuronidation and increased formation of
      the hepatotoxic oxidation metabolites, which was independent of zidovudine
      therapy.

PMID- 9151290
TI  - Modeling neuronal degeneration in the rodent hippocampus: an approach for
      studying degenerative neuropathology in dementia.

PMID- 9151291
TI  - Blockade of protein kinase C is involved in the inhibition by cycloheterophyllin
      of neutrophil superoxide anion generation.
AB  - Cycloheterophyllin, a prenylflavone, inhibited the superoxide anion (O2-)
      generation from formylmethionyl-leucyl-phenylalanine (fMLP)- and phorbol 12
      myristate 13-acetate (PMA)-stimulated rat neutrophils in a concentration
      dependent manner with IC50 values of 47.0 +/- 5.0 and 1.7 +/- 0.4 microM,
      respectively. Cycloheterophyllin had no effect on O2- generation in xanthine
      xanthine oxidase system and during dihydroxyfumaric acid (DHF) autoxidation.
      Cycloheterophyllin exerted a concentration-dependent inhibition of neutrophil
      cytosolic protein kinase C (PKC) and rat brain PKC, but had no effect on porcine
      heart protein kinase A (PKA). Unlike staurosporine, cycloheterophyllin did not
      affect the trypsin-treated rat brain PKC. [3H]Phorbol 12,13-dibutyrate ([3H]PDB)
      binding to neutrophil cytosolic PKC was significantly suppressed by
      cycloheterophyllin. However, cycloheterophyllin had negligible effect on the PMA
      induced membrane translocation of PKC-beta and PKC-delta in neutrophils.
      Moreover, the fMLP-induced [Ca2+]i elevation and inositol trisphosphate (IP3)
      formation of neutrophils were not affected by cycloheterophyllin at
      concentrations which significantly suppressed the O2- generation. In cell-free
      system, addition of arachidonate (AA) into the mixture of cytosol and membrane
      fractions of the resting neutrophils to make NADPH oxidase assembly and
      activation. Cycloheterophyllin had no effect on O2- generation in AA-activated
      cell-free system. These results suggest that the suppression of PKC activity
      through the interaction with the regulatory region of PKC is involved in the
      inhibition by cycloheterophyllin of the O2- generation in rat neutrophils.

PMID- 9151292
TI  - Histamine H1 receptors in C6 glial cells are coupled to calcium-dependent
      potassium channels via release of calcium from internal stores.
AB  - We investigated the action of histamine on C6-astroglioma cells using patch clamp
      recording and intracellular calcium measurement. Application of 100 microM
      histamine hyperpolarized the resting membrane potential and increased free
      intracellular calcium. Membrane hyperpolarization was accompanied by a decrease
      in input resistance. The effect of histamine was reversible and responses
      persisted following repeated applications. In voltage clamp experiments histamine
      elicited an outward current associated with a conductance increase and a reversal
      potential near the Nernst potential for potassium. The action of histamine was
      blocked by mepyramine but not by cimetidine or thioperamide suggesting that a H1
      receptor mediated the response. Quinidine and charybdotoxin, but not apamin,
      blocked the hyperpolarization. Buffering internal calcium with BAPTA diminished
      the activation of the potassium channel, suggesting a calcium-dependent K(+)
      channel, which was also found to be regulated by protein kinase C and
      phosphatases. The increase in intracellular calcium was not dependent on external
      calcium or sensitive to pertussis toxin, cholera toxin, forskolin or 8-bromo
      cAMP. Both the hyperpolarization and the increase in intracellular calcium were
      blocked by thapsigargin or the phospholipase C inhibitor U73122. These results
      indicate that histamine liberates calcium from internal stores by activation of
      phospholipase C which in turn leads to an increase of intracellular Ca2+ and
      thereby to the activation of a calcium-dependent potassium channel in C6 glial
      cells.

PMID- 9151294
TI  - Role of central nicotinic and beta-adrenergic receptors in the onset and further
      development of tail-tremor induced by repeated nicotine administration to rats.
AB  - The effects of nicotinic and beta-adrenergic receptor antagonists on tail-tremor
      induced by repeated nicotine administration were investigated in rats. The daily
      administration of nicotine (0.5 mg/kg/day, s.c.) for 8 days resulted in an
      augmentation of tail-tremor. However, repeated administration of dimethyl phenyl
      piperazinium iodide (1 mg/kg/day, s.c.) for 8 days did not cause tail-tremor.
      Mecamylamine (0.5 mg/kg, i.p), administered before the nicotine injection on each
      day, abolished the tail-tremor. After discontinuation of the mecamylamine
      treatment, nicotine injections caused tail-tremor augmentation. Propranolol (20
      mg/kg, i.p.), administered before the nicotine on each day, suppressed the
      appearance of tail-tremor. After the discontinuation of propranolol treatment,
      the degree of tail-tremor induced by a single injection of nicotine on day 9 was
      much greater in the propranolol-treated group than in the saline-treated control
      group. Neither carteolol (20 mg/kg, i.p.) nor metoprolol (20 mg/kg, i.p.)
      treatment showed such effects. Intraspinal injection of 6-hydroxydopamine
      markedly enhanced the tail-tremor induced on the first day of nicotine injection.
      This effect became more intense on subsequent administration of nicotine. The
      enhanced tail-tremor following 6-hydroxydopamine treatment was abolished by
      mecamylamine (0.5 and 1 mg/kg, i.p.), and was suppressed by propranolol (5-20
      mg/kg, s.c.) in a dose-dependent manner. These results suggest that central
      nicotinic receptors are essential for the onset and for the further development
      of tail-tremor induced by the repeated administration of nicotine, and that beta
      2-adrenoceptors are associated with the tremor mechanism. Moreover, spinal
      noradrenergic mechanisms may be involved in the manifestation of this phenomenon.

PMID- 9151293
TI  - Involvement of 5-hydroxytryptamine and bradykinin in the hyperalgesia induced in
      rats by collagenase from Clostridium histolyticum.
AB  - The involvement of bradykinin, 5-hydroxytryptamine, substance P and prostanoids
      in the hyperalgesia elicited by collagenase in rat paw was investigated.
      Collagenase (100 micrograms) induced a slight hyperalgesia in kininogen deficient
      rats in comparison with the behavioural response obtained in normal rats.
      Lisinopril (10(-5) M), and angiotensin-converting enzyme inhibitor, increased the
      duration of the hyperalgesia elicited in normal rats. Ondansetron (0.5 to 5
      mumol/kg), a 5-HT3 antagonist, suppressed the hyperalgesia as did methysergide
      (1.1 to 11 mumol/kg), a mixed 5-HT1 and 5-HT2 receptor antagonist. However, the
      hyperalgesia was not modified by RP 67580 (1.8 to 18 mumol/kg), a NK1 receptor
      antagonist, and was only slightly delayed by indomethacin (2 mg/kg), a cyclo
      oxygenase inhibitor. The oedema-promoting effect of 5-HT (6 nmol) was inhibited
      by methysergide but not by ondansetron. The swelling induced by collagenase in
      rat paw was reduced by methysergide but not by ondansetron. We conclude that the
      behavioural response induced by collagenase depends on an interactions between
      bradykinin and 5-HT. Prostanoids play a minor role in the beginning of the
      reaction whereas substance P is not significantly involved in this hyperalgesia.

PMID- 9151295
TI  - Cholecystokinin-8S increases dynorphin B, aspartate and glutamate release in the
      fronto-parietal cortex of the rat via different receptor subtypes.
AB  - The effect of sulphated cholecystokinin-8 (CCK-8S) on extracellular dynorphin B,
      aspartate, glutamate and GABA levels in the rat fronto-parietal cortex was
      investigated with in vivo microdialysis. The peptide was infused through the
      microdialysis probe trying to mimic local CCK-8S release. Basal levels of
      dynorphin B were around 20 pM, aspartate 100 nM, glutamate 600 nM and GABA 30 nM.
      CCK-8S (10 microM) induced a approximately 3-fold increase in extracellular
      dynorphin B, aspartate and glutamate levels, while GABA levels were only slightly
      increased. The effect of CCK-8S was restricted to the stimulated neocortex.
      Systemic pretreatment with the CCKB antagonist, L-365, 260, but not with the CCKA
      antagonist, L-364, 718, significantly antagonised the effect of CCK-8S on
      cortical dynorphin B and aspartate release. However, both CCKA and CCKB
      antagonists inhibited the increase in cortical glutamate levels. Thus, the
      present results indicate that cortical CCK release exerts a stimulatory
      modulation on cortical dynorphin B and aspartate release via the CCKB receptor
      subtype, and on glutamate release via both CCKA and CCKB receptor subtypes.
      Considering electrophysiological evidence that CCK increases neuronal firing
      rates in many brain regions, it may be suggested that CCK represents a
      stimulatory system modulating the function of the neocortex.

PMID- 9151296
TI  - Involvement of mu- and delta-opioid receptors in the effects of systemic and
      locally perfused morphine on extracellular levels of dopamine, DOPAC and HVA in
      the nucleus accumbens of the halothane-anaesthetized rat.
AB  - The effects of systemic and intra-accumbens infusion of morphine on the
      extracellular level of dopamine (DA) and its metabolites, DOPAC and HVA, were
      investigated in the nucleus accumbens (NAcc) of halothane-anaesthetized rats
      using in vivo microdialysis. Morphine in a dose of 1 or 5 mg/kg i.v. produced a
      significant increase (60-100% of baseline levels) in the extracellular level of
      DA for at least 3 h. Morphine at 5, but not 1 mg/kg, produced a small (10-15%)
      but significant reduction in the level of DOPAC when compared with saline in the
      first h following injection. Pretreatment with the preferential mu-opioid
      receptor antagonist naloxone in a dose of 1 or 3 mg/kg i.p. significantly blocked
      the morphine-induced changes in the extracellular levels of DA and DOPAC.
      Pretreatment with the selective delta-opioid receptor antagonist, naltrindole, at
      1 mg/kg i.p. blocked only the morphine-induced decrease in DA metabolism.
      Furthermore, in the presence of naltrindole, systemic morphine induced a large
      and long-lasting increase in the level of DOPAC and HVA, which was significantly
      higher than in rats receiving combinations of saline/water + saline, saline/water
      + morphine and naltrindole + saline. When applied directly into the NAcc,
      morphine at concentrations of 125, 250 and 500 ng infused over 10 min produced a
      dose-related increase in the extracellular level of accumbens DA with either no
      effect or a small reduction in the level of DOPAC and HVA. The effects of intra
      accumbens morphine on DA levels were significantly blocked by pretreatment with
      i.p. naltrindole but not naloxone. These results indicate that, while systemic
      morphine probably increases DA via activation of mu-opioid receptors, local
      perfusion of morphine increases DA in the NAcc via activation of delta-opioid
      receptors located in the NAcc. Furthermore, under the conditions of the study, it
      appears that activation of mu- and delta-opioid receptors by morphine
      respectively increases and decreases DA metabolism.

PMID- 9151297
TI  - Conditioned place preference: no tolerance to the rewarding properties of
      morphine.
AB  - The effect of repeated morphine administration on conditioned place preference
      (CPP) using a novel treatment schedule, i.e., drug treatment was always
      contingent with the conditioned environmental stimuli, was investigated. We also
      examined whether changes in the mu- and kappa-opioid receptor binding occurred in
      the brain of morphine-treated animals. Intraperitoneal (i.p.) administration of
      morphine (2 and 10 mg/kg) induced a place preference after 8 daily conditioning
      trials (4 morphine injections on alternate trials), the level of preference being
      the same with the two doses of the opiate. No change in place preference was
      observed in the morphine-treated rats at 2 mg/kg, when animals were further
      trained up to a total of 32 conditioning trials (16 morphine injections).
      Conversely, after 20 conditioning trials (10 morphine injections), a stronger CPP
      response developed in the morphine-treated rats at 10 mg/kg. Signs of morphine
      withdrawal were never detected in morphine-treated rats during the experiment.
      Loss of body weight (index of opiate dependence) was not observed either 24 h or
      48 h after the last morphine administration. mu- and kappa-opioid receptor
      density and affinity were not affected by repeated morphine administrations at
      either dose. The results demonstrate that no tolerance develops to the rewarding
      properties of morphine. Indeed, a sensitisation effect may occur at increasing
      doses of the opiate. Furthermore, changes in the rewarding effect of morphine are
      not dependent upon alterations in opioid receptors involved in the reinforcing
      mechanisms.

PMID- 9151298
TI  - Prevention by morphine of apomorphine- and oxytocin-induced penile erection and
      yawning: involvement of nitric oxide.
AB  - The possible involvement of nitric oxide in the prevention by morphine of
      apomorphine- and oxytocin-induced penile erection and yawning was investigated by
      measuring the concentration of NO2- and NO3- in the dialysate obtained with a
      vertical microdialysis probe implanted in the paraventricular nucleus of the
      hypothalamus of male rats. Either apomorphine (80 micrograms/kg s.c.) or oxytocin
      (30 ng i.c.v.) increased significantly basal NO2- and NO3- concentration in the
      paraventricular dialysate, penile erection and yawning. Morphine (1.5 and 10
      mg/kg i.p.) prevented dose-dependently either apomorphine or oxytocin responses
      when given 15 min before apomorphine or oxytocin. Prevention by morphine of
      apomorphine and oxytocin responses was abolished by naloxone (3 mg/kg i.p.) given
      15 min before morphine. Morphine prevented apomorphine and oxytocin responses
      also when given in the lateral ventricles or directly in the paraventricular
      nucleus. In contrast, the selective agonist of the kappa opioid receptor subtype
      U-69,593 was found to be ineffective. The present results confirm previous
      findings showing that morphine acts through mu receptors in the paraventricular
      nucleus to prevent apomorphine and oxytocin-induced penile erection and yawning
      and suggest that this morphine effect is mediated by a decreased activity of
      nitric oxide in the paraventricular nucleus of the hypothalamus.

PMID- 9151299
TI  - Blockade of voltage-sensitive sodium channels by NS-7, a novel neuroprotective
      compound, in the rat brain.
AB  - The effects of 4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy) pyrimidine
      hydrochloride (NS-7), a novel neuroprotective compound, on the voltage-sensitive
      sodium channels (VSSC) were examined in the rat brain and cardiac myocytes. NS-7
      inhibited [3H]batrachotoxinin A 20 alpha-benzoate (BTX) binding (neurotoxin
      receptor site 2) in brain membranes with a Ki value of 1 microM, while the
      compound was less effective in the cardiac myocytes (Ki = 13 microM). Aconitine,
      on the other hand, inhibited [3H]BTX binding to brain membranes and cardiac
      myocytes with the same potency. In contrast. NS-7 had no affinity for
      [3H]saxitoxin binding in brain (neurotoxin receptor site 1). In superfused slices
      of the rat cerebral cortex, NS-7 inhibited the veratridine (5 microM)-evoked
      glutamate release in a concentration-dependent manner, the IC50 value of which
      was 7.7 microM, whereas the compound showed a weak and not significant
      suppression of KCl-evoked glutamate release. The tissue concentrations of NS-7 in
      the rat cerebral cortex and heart were 89 and 28 nmole/g tissue, respectively, 5
      min after its intravenous injection (8 mg/kg). Furthermore, in the cerebral
      cortex, NS-7 distributed preferentially to the membrane-enriched synaptosomal
      fraction. Since neurotoxin receptor site 2 is located in the transmembrane region
      of the VSSC moiety, the channel function may be substantially inhibited by a
      peripheral administration of NS-7. These results suggest that the blockade of
      neurotoxin receptor site 2 of VSSC in the brain contributes to the
      neuroprotective action of NS-7.

PMID- 9151300
TI  - The effects of catechol on various membrane conductances in lumbar sympathetic
      postganglionic neurones of the guinea-pig.
AB  - The effects of catechol on membrane properties in lumbar sympathetic
      postganglionic neurones isolated from guinea-pigs were studied in vitro in
      current and voltage clamp using single intracellular microelectrodes. Neurones
      with properties characteristic of two previously described classes of neurone
      (phasic and tonic) were studied. Catechol (3-12 mM) produced a few mV
      depolarization and a dose-dependent increase in membrane resistance which were
      both larger in tonic than in phasic neurones. In the presence of catechol, both
      phasic and tonic neurones fired only a single action potential at the beginning
      of a maintained depolarizing current step. In both neurone types, catechol
      reduced action potential amplitude and slowed its time course. The peak of the
      afterhyperpolarization became delayed and reduced in amplitude, particularly in
      tonic neurones. The time constant of inactivation of IA was reduced by catechol
      without change in the voltage sensitivity of activation or inactivation: IC50 was
      3 mM in phasic and 4 mM in tonic neurones. Catechol also blocked a slow voltage
      activated K+ current (resembling ID) that was present in many tonic neurones.
      Catechol did not modify the slow calcium-activated potassium current (gKCa1) or
      the anomalous rectifier; neither did it appear to affect the fast calcium
      activated potassium current (IC) or the delayed rectifier. Catechol did not
      change the overall rate of spontaneous synaptic activity nor enhance the release
      of quanta of ACh from preganglionic terminals evoked by nerve stimulation. We
      conclude that, in addition to blocking IA, catechol blocks the slow ID-like
      current in sympathetic neurones. It also has a profound effect on the action
      potential probably by increasing inactivation of voltage-dependent Na+ channels.
      The change from tonic to phasic discharge in tonic neurones cannot be attributed
      solely to its effects on IA.

PMID- 9151301
TI  - Rat big endothelin-1-induced bronchoconstriction and vasoconstriction in the
      isolated perfused rat lung: role of endothelin converting enzyme and neutral
      endopeptidase 24.11.
AB  - Treatment of animals with big endothelin-1 (bET) causes pulmonary hypertension
      and bronchoconstriction, both in vivo and in perfused lungs. The biological
      activity of bET requires proteolytic cleavage to ET-1 by endothelin converting
      enzymes (ECE) and possibly other proteases such as neutral endopeptidase 24.11
      (NEP 24.11). Since the role of NEP 24.11 in the physiological activation of bET
      is unclear, we investigated the effects of the selective NEP 24.11 inhibitor
      thiorphan on bET-induced vaso- and bronchoconstriction in the isolated perfused
      rat lung. We also studied the effects of phosphoramidon and (S)-2-biphenyl-4-yl-1
      (1H-tetraol-5-yl)-ehtylaminomethylphosphonic acid (CGS-26303), i.e. agents which
      block not only NEP 24.11 but also ECE. The bET-induced vasoconstriction was much
      less prominent than the bronchoconstriction, i.e. after exposure for 110 min
      vascular and airway conductance were decreased by 33% and 80% respectively. The
      small bET-induced vasoconstriction was attenuated to a similar degree by
      pretreatment with any of the three protease inhibitors. However, thiorphan up to
      a concentration of 10 microM had only little effect on the bET-induced
      bronchoconstriction, while 10 microM phosphoramidon or CGS-26303 provided half
      maximal and 100 microM phosphoramidon complete protection in this model. This
      profile of inhibitor action suggests that in rat lung ECE is the major enzyme
      responsible for activation of bET.

PMID- 9151303
TI  - Cholecystokinin-JMV-180 and pilocarpine are potent inhibitors of cholecystokinin
      and carbachol actions on guinea pig pancreatic acinar cells.
AB  - The release of amylase and the elevation of cytoplasmic Ca2+ concentration
      ([Ca2+]i) in response to cholecystokinin-octapeptide (CCK-8), the cholecystokinin
      analogue JMV-180, the stable choline ester carbamylcholine (carbachol) and the
      muscarinic agonist pilocarpine were studied in guinea-pig pancreatic acinar
      cells. The maximal amylase and [Ca2+]i responses to JMV-180 and pilocarpine were
      12-15% of the corresponding responses to CCK-8 and carbachol. The amylase and
      [Ca2+]i responses to maximal concentrations of CCK-8 and carbachol were inhibited
      in concentration-dependent manners by JMV-180 and pilocarpine, respectively. In
      individual acinar cells, JMV-180 and pilocarpine like low concentrations of CCK-8
      and carbachol caused oscillations of [Ca2+]i. The sustained [Ca2+]i responses to
      maximal concentrations of CCK-8 and carbachol were transformed into oscillatory
      responses during simultaneous exposure to JMV-180 and pilocarpine, respectively.
      Maximal concentrations of JMV-180 and pilocarpine did not cause homologous or
      heterologous desensitization of the [Ca2+]i responses but inhibited
      desensitization evoked by maximal concentrations of CCK-8 or carbachol. JMV-180
      and pilocarpine acted as weak, partial agonists exhibiting effective inhibition
      of the acinar cell responses to full agonists. The effects appeared to be best
      explained by interactions with two forms of the respective receptor with JMV-180
      and pilocarpine acting as partial agonists for one state of the receptor and as
      antagonist for the second state.

PMID- 9151302
TI  - Leukotriene-evoked cyclic chloride secretion is mediated by enteric neuronal
      modulation in guinea-pig colon.
AB  - Short term exposure to leukotrienes evoked a well known nerve mediated increase
      in short circuit current. It is unknown whether leukotrienes evoke in addition
      oscillations in chloride secretion, as has been reported for some of the other
      mediators released during inflammation. Therefore, the aim of this study was to
      characterize the effects of a long time exposure of leukotrienes on mucosal
      functions. Conventional Ussing chamber, and intracellular recording techniques
      were used to investigate the actions of leukotriene D4 and C4 on short-circuit
      current and excitability of submucosal neurons in guinea-pig distal colon. In
      Ussing chambers, long term exposure to leukotriene D4 or C4 evoked rhythmic
      oscillations in short-circuit current in 35% and 50% of tissues, respectively.
      These current bursts were blocked by tetrodotoxin, atropine, hexamethonium and
      piroxicam. Secretory response to short term exposure of leukotrienes was
      significantly higher in tissues exhibiting current bursts. Likewise, the
      potentiating effects of leukotrienes on the response to field stimulation was
      only observed in tissues exhibiting current bursts. In intracellular recording
      experiments, leukotriene C4 evoked activation of submucosal neurons that was
      partly sensitive to indomethacin; no oscillations in neuronal excitability could
      be demonstrated. Results suggested that long term exposure to leukotrienes evoked
      current bursts that were mediated by neural, cholinergic mechanisms as well as
      endogeneous prostaglandins.

PMID- 9151304
TI  - Involvement of both L- and N-type voltage-dependent Ca2+ channels in KCl- and
      veratridine-evoked transmitter release from non-adrenergic, non-cholinergic
      nerves in the rabbit iris sphincter muscle.
AB  - To determine which types of voltage-dependent Ca2+ channels mediate tachykinin
      release in the isolated rabbit iris sphincter muscle, we examined the effects of
      several Ca2+ channel modulators on contractions induced by either an elevation of
      the extracellular KCl concentration or application of the Na+ channel activator
      veratridine. Contractions caused by either 45.9 mM KCl or veratridine (10 microM)
      were inhibited by spantide (10 microM), a tachykinin receptor antagonist, and
      capsaicin (10 microM), a tachykinin-depleting agent, but were not changed by
      atropine. Nicardipine, an L-type Ca2+ channel blocker, inhibited contractions
      induced by KCl and veratridine in a concentration-dependent manner. omega
      Conotoxin GVIA (1 microM), an N-type Ca2+ channel blocker, inhibited only
      contractions induced by lower concentrations of KCl, both when applied alone and
      when combined with nicardipine. Bay K 8644, an L-type Ca2+ channel activator,
      caused a spantide- and nicardipine-sensitive contraction in muscles partially
      depolarized with 15.9 mM KCl, and enhanced contractions induced by 15.9 mM KCl
      and veratridine (2 microM). omega-Agatoxin IVA (0.3 microM), a P-type voltage
      dependent Ca2+ channel blocker, did not affect contractions induced by either KCl
      or veratridine. Contractions induced by exogenous substance P were not modified
      by any of the Ca2+ channel blockers or by Bay K 8644. These results suggest that,
      in the rabbit iris sphincter muscle. L- and N-type voltage-dependent Ca2+
      channels are involved in neurotransmitter release from tachykininergic nerves
      elicited by high KCl and by veratridine.

PMID- 9151305
TI  - A long-lasting hypotensive effect of topical diltiazem on the intraocular
      pressure in conscious rabbits.
AB  - The effect of calcium channel blockers on intraocular pressure and aqueous humor
      dynamics remains still controversial, although preliminary evidence suggests that
      these drugs may be beneficial in the management of ocular hypertension and low
      tension glaucoma. Having previously reported the ocular hypotensive effect of
      topical nifedipine and verapamil in albino rabbits, the original aim of the
      present work was to evaluate the effect of topical diltiazem on aqueous humor
      dynamics in this species. Intraocular pressure was measured with a manual
      applanation tonometer. The experiments examining the ocular actions of diltiazem
      were carried out in two stages. In the first one, short term effects of topical
      diltiazem on intraocular pressure were studied in groups of 13 albino rabbits
      receiving 8 different doses of the drug in order to obtain a dose-response curve.
      Tonographies were performed in 13 anaesthetized animals before and 90 min after
      drug instillation. In a second phase, the persistence of the effect of diltiazem
      on intraocular pressure was examined in 6 groups of 10 rabbits each receiving
      three different doses of the drug. Topical diltiazem was found to lower
      intraocular pressure in a dose-related fashion. The maximum response to diltiazem
      was greater and the ED50 lower than those previously reported for nifedipine and
      verapamil. In the tonographic study, diltiazem was shown to reduce the facility
      of aqueous humor outflow and inflow. Diltiazem exhibited a long lasting effect on
      intraocular pressure that was again dose-related. Depending on the dose
      administered, the calculated time necessary for the peak effect to be halved
      ranged from 0.6 to 7.0 days. Due to the intensity and the persistence of its
      intraocular pressure-lowering effect, diltiazem shows great potential for the
      treatment of glaucoma, since a daily or less frequent administration may be
      enough to control ocular hypertension.

PMID- 9151306
TI  - Cardiac electrophysiological actions of NS-21 and its active metabolite, RCC-36,
      compared with terodiline.
AB  - Terodiline, an anticholinergic drug with a Ca2+ blocking action, is thought to be
      associated with torsade de pointes, a serious ventricular tachycardia. NS-21 is a
      newly developed drug for the treatment of urinary frequency and urinary
      incontinence and it has pharmacological properties similar to those of
      terodiline. It remains unknown, however, whether NS-21 and its active metabolite,
      RCC-36, have any proarrhythmic activity. The electrophysiological properties of
      NS-21 and RCC-36 were examined in guinea pig ventricular myocytes and were
      compared with those of terodiline using the whole-cell patch-clamp technique. NS
      21, RCC-36 and terodiline inhibited L-type Ca2+ currents in a concentration
      dependent manner with IC50 values of 27.0, 27.0 and 33.5 microM, respectively. At
      a concentration of 10 microM, terodiline inhibited both the time-dependent
      current and the tail current of the delayed rectifier K+ current, with the latter
      being significantly inhibited at voltages more positive than +10 mV. In contrast,
      NS-21 and RCC-36 had almost no effect on either of these currents. Terodiline
      also inhibited the inward rectifier K+ current significantly at voltages more
      negative than -100 mV, whereas NS-21 and RCC-36 had little effect. If the
      proarrhythmic activity of terodiline resulted primarily from the combined
      inhibition of K+ and Ca2+ currents, one might expect that NS-21 and RCC-36, which
      inhibit L-type Ca2+ currents without affecting either the delayed rectifier K+
      current or the inward rectifier K+ current, would not share the proarrhythmic
      activities of terodiline.

PMID- 9151307
TI  - Inhibitory effects of NS-21, a novel drug for urinary incontinence, and its
      active metabolite, RCC-36, on L-type calcium currents in isolated guinea pig
      detrusor smooth muscle cells.
AB  - The inhibitory effects of NS-21, a newly developed drug for the treatment of
      urinary frequency and urinary incontinence, and its active metabolite, RCC-36, on
      L-type Ca2+ currents (ICa) in guinea pig detrusor smooth muscle cells have been
      compared to those of terodiline by a whole-cell patch-clamp technique. Like
      terodiline (10 microM), both NS-21 (10 microM) and RCC-36 (10 microM) induced a
      sizeable decrease in ICa elicited from a holding potential of -60 mV without
      changing the current-voltage relationship. The three drugs shifted the
      inactivation curves for ICa in the hyperpolarizing direction by 13 to 20 mV but
      had no effect on the activation curves for ICa resulting in a decrease in the
      calcium window current. The inhibitory effects of NS-21 and RCC-36 were greater
      than those of terodiline. The three drugs inhibited ICa in a concentration- and
      holding-potential-dependent manner. The IC50 values at a holding potential of -60
      mV were 7.9 microM for NS-21, 6.4 microM for RCC-36, and 5.9 microM for
      terodiline, and at -40 mV they were 1.3, 1.2, and 3.5 microM, respectively. The
      ratio calculated by dividing the IC50 value at -60 mV by the value at -40 mV was
      6.1, 5.3 and 1.7, respectively, indicating that the inhibitory effects of NS-21
      and RCC-36 on ICa were more sensitive to voltage than those of terodiline. These
      results suggest that NS-21 and RCC-36 could be more effective in the treatment of
      urinary bladder ailments, such as urinary frequency and urinary incontinence.

PMID- 9151308
TI  - Batten disease, a twenty-eight-year struggle: past, present and future.

PMID- 9151309
TI  - Neuronal ceroid lipofuscinoses in Scandinavia. Epidemiology and clinical
      pictures.
AB  - The epidemiology of neuronal ceroid lipofuscinoses (NCL) in Scandinavia was
      studied. For juvenile NCL 40 Swedish living patients were identified. The
      corresponding number for Finland was 61, for Norway 28, for Denmark 16 and for
      Iceland three. The prevalence of juvenile NCL was thus 4.6, 12.2, 6.5, 3.1 and 11
      per million inhabitants in Sweden, Finland, Norway, Denmark, and Iceland,
      respectively. For calculating incidence the years 1976-85 were used. The
      incidence was 2.2 per 100,000 live births in Sweden, 4.8 in Finland, 3.7 in
      Norway, 2.0 in Denmark, and 7.0 in Iceland. Late infantile NCL was found in five
      Swedish children, including one variant form, CLN5. This gives a prevalence of
      about 0.6 per million. In Finland 13 cases gave a prevalence of 2.6 per million
      with the variant form in 80% of cases. In Norway, three children corresponded to
      a prevalence of 0.7 per million and one case in Iceland to 3.8 per million. No
      Danish cases were reported. As for infantile NCL, sixteen Swedish cases have been
      diagnosed during the 27-year period 1968-95, six are presently alive. This gives
      an estimated prevalence of 0.7 per million and an incidence of 0.6 per 100,000.
      The prevalence and incidence of infantile NCL in Finland were 5.4 per million and
      5 per 100,000, respectively. The prevalence in Norway was 0.2 per million
      inhabitants. The variability of onset, clinical course and symptoms in the
      Swedish cases of juvenile and infantile NCL were analysed.

PMID- 9151310
TI  - From locus to cellular disturbances: positional cloning of the infantile neuronal
      ceroid lipofuscinosis gene.
AB  - Neuronal ceroid lipofuscinoses (NCL) represent a group of common progressive
      encephalopathies of children with a global incidence of 1 in 12,500. NCL are
      divided into three autosomal recessive subtypes, all assigned to different
      chromosomal loci. The infantile subtype of NCL (INCL) is characterized by early
      visual loss and mental deterioration, and leads to a vegetative state of the
      patients by 3 years of age. We pursued the identification of the gene defective
      in INCL, enriched in the Finnish population by a positional cloning approach and
      identified mutations in the palmitoyl-protein thioesterase (PPT) gene in INCL
      patients. We have further shown that PPT represents a novel lysosomal enzyme and
      is routed to the lysosomes via the mannose 6-phosphate receptor-mediated pathway.
      The worldwide most common mutation in the PPT gene, INCLFin, results in the
      deficient routing of the mutant PPT to lysosomes and undetectable enzyme activity
      in the brain tissue of patients. Our results suggest that INCL can be classified
      as a new member of lysosomal enzyme deficiencies.

PMID- 9151311
TI  - Structure of the CLN3 gene and predicted structure, location and function of CLN3
      protein.
AB  - The genomic sequence of the human CLN3 gene, which is defective in juvenile onset
      neuronal ceroid lipofuscinosis (Batten disease) is being delineated using a
      variety of methods. A Saccharomyces cerevisiae gene, YHC3 (for Yeast Homologue to
      human CLN3), which is highly similar to the human disease gene, has been
      identified by computer-aided homology searching. Topology predictions indicate
      the CLN3 protein contains six transmembrane segments. Most similarity between the
      human and yeast proteins lies either in the transmembrane segments or along one
      face of the predicted protein structure.

PMID- 9151312
TI  - Strategy for mutation detection in CLN3: characterisation of two Finnish
      mutations.
AB  - A strategy for detection of mutations in CLN3, the gene for Batten disease or
      juvenile onset neuronal ceroid lipofuscinosis, has been devised using a technique
      which detects conformation polymorphisms and direct sequencing of genomic DNA
      fragments. We define two mutations found uniquely in Finnish patients, one a
      large deletion (2.8 kb), the other a point mutation affecting the 5'splice donor
      site of an intron.

PMID- 9151313
TI  - Cross-species homology of the CLN3 gene.
AB  - A murine cDNA clone was isolated by screening a mouse cDNA library with the human
      CLN3 cDNA. Sequence analysis indicates that the corresponding CLN3 proteins are
      highly homologous. We have compared these with recently identified CLN3 sequences
      from the dog, the nematode C. elegans, and baker's yeast S. cerevisiae. The CLN3
      protein is remarkably conserved across eukaryotic species. Several protein
      modification sites which may be crucial for the function of the protein are
      conserved.

PMID- 9151314
TI  - Genetic linkage analysis of a variant of juvenile onset neuronal ceroid
      lipofuscinosis with granular osmiophilic deposits.
AB  - A number of variant forms of the neuronal ceroid lipofuscinoses (NCL) have been
      described and remain unmapped. The genes for infantile (CLN1), juvenile (CLN3)
      and Finnish-variant late-infantile (CLN5) have previously been mapped to
      chromosome regions 1p32, 16p12 and 13q21.1-32 respectively. The locus for a
      variant form of juvenile onset NCL characterised by cytosomal granular
      osmiophilic deposits (GROD) has been excluded from the CLN3 region of chromosome
      16. This study describes the outcome of genetic linkage analysis in four families
      with this variant at the loci for the CLN1 and CLN5 genes. Using highly
      informative microsatellite markers tightly linked to the CLN5 locus we have
      excluded the JNCL variant with GROD from this region. Marker typing across the
      CLN1 region suggests that JNCL with GROD may be an allelic variant of infantile
      NCL.

PMID- 9151315
TI  - The mechanism and functional roles of protein palmitoylation in the nervous
      system.
AB  - Palmitoylation refers to the covalent attachment of long-chain fatty acids,
      mostly palmitic acid, to the side chain of cysteine residues of proteins. In
      recent years, a considerable number of functionally relevant nervous system
      proteins including ion channels, neurotransmitter receptors, signal transduction
      components and cell-adhesion molecules have been found to be palmitoylated.
      However, the lack of a generalized and unambiguous role for the fatty acids in
      these proteins has questioned the importance of palmitoylation in the functioning
      of the nervous system. Last year, it was found that the deficiency of palmitoyl
      protein thioesterase (PPT), one of the enzymes responsible for the removal of
      palmitate from proteins, is the underlying cause of infantile neuronal ceroid
      lipofuscinosis (INCL). This finding not only constitutes a step forward in
      elucidating the pathogenesis of INCL, but it also provides new impetus in the
      search for the function(s) of protein palmitoylation. This work succinctly
      outlines the molecular mechanisms involved in dynamic acylation and the potential
      biological role(s) of this modification, and it constitutes an introduction to
      those presentations in this issue which specifically deal with the pathogenic
      mechanisms of INCL.

PMID- 9151316
TI  - Palmitoyl-protein thioesterase and the molecular pathogenesis of infantile
      neuronal ceroid lipofuscinosis.
AB  - Palmitoyl-protein thioesterase (PPT) has recently been shown to be the defective
      enzyme underlying the infantile form of neuronal ceroid lipofuscinosis (INCL). In
      this paper, we review the enzymology of PPT, evidence for its localization in
      lysosomes, and recent advances in understanding the metabolic defect caused by
      PPT deficiency. Absence of PPT activity in lysosomes isolated from INCL
      lymphoblasts is demonstrated. A model for the formation of the storage bodies in
      INCL involving defective autophagocytic proteolysis is proposed.

PMID- 9151317
TI  - Low molecular weight storage material in infantile ceroid lipofuscinosis (CLN1).
AB  - The identification of the genetic defect in CLN1 as a palmitoyl-protein
      thioesterase deficiency initiated a search for the lysosomal storage material.
      Pulse-chase labelling of fibroblasts and lymphoblastoid cell lines with
      [35S]cysteine revealed the presence of lipid [35S]cysteine material in CLN1
      fibroblasts and not in controls, CLN2 or CLN3 patients or other patients with
      lipidosis. A single band comigrated with the acylcysteine standard and labelling
      with [3H]palmitate showed a band of material which eluted from the silicic acid
      column with the phospholipid fraction and which co-migrated with the lipid
      [35S]cysteine band. The storage material is tentatively identified as
      palmitoylcysteine.

PMID- 9151318
TI  - Expression studies of CLN3 protein.
AB  - Expression of the gene for Batten disease (CLN3) was studied in Escherichia coli
      and in a cell-free rabbit reticulocyte expression systems. A full-length
      recombinant fusion CLN3 protein was not produced in the bacterial systems used.
      However, both N-terminal fragment encompassing 246 amino acids and short C
      terminal fragment containing 428-438 amino acids of the CLN3 protein were
      successfully overexpressed in bacteria. Further studies showed that the C
      terminal sequence of the CLN3 protein corresponding to the 356-438 amino acid
      residues was responsible for inhibition of protein synthesis in bacteria. The
      full-length CLN3 gene product was readily synthesized in vitro in the cell-free
      rabbit reticulocyte expression system. The product obtained, corresponding to
      core CLN3 protein, showed an approximate molecular weight of 43 kDa.
      Immunoprecipitation of this product with pAb to 4-19 amino acids of the CLN3
      protein allows us to suggest that CLN3 protein translation starts at Met-1.

PMID- 9151319
TI  - Upregulation of Bcl-2 and elevation of ceramide in Batten disease.
AB  - The late infantile and juvenile variants of Batten disease are genetically
      distinct neurodegenerative disorders. Hallmarks of Batten disease include
      cognitive and motor decline, seizures and blindness due to retinitis pigmentosa.
      Recently, the CLN3 gene responsible for the juvenile variant has been cloned.
      Also, apoptosis was proven to be the mechanism by which neurons and
      photoreceptors die. This paper provides mechanistic support for the occurrence of
      apoptosis in this disease: There was marked upregulation of Bcl-2 in brain from
      the late infantile and juvenile types at the protein and RNA levels both by
      immunocytochemistry and by Northern blot analysis; there were also a 42% to 197%
      increase in brain ceramide determinations in brains from three patients with the
      juvenile type and three patients with the late infantile type. Double
      immunolabeling of brain sections for apoptosis and Bcl-2 supported a protective
      role for Bcl-2 in the juvenile form of Batten disease. These results raise the
      possibility that the intact CLN3 gene is normally antiapoptotic, and that it
      could be an upstream regulator of ceramide.

PMID- 9151320
TI  - Farnesylation of Batten disease CLN3 protein.
AB  - The carboxyl terminal of the predicted amino acid sequence of the Batten disease
      CLN3 gene protein is CQLS. This motif is expected to be a site for farnesylation
      at the cysteine residue. In order to determine whether this is indeed
      farnesylated we have carried out the in-vitro prenylation of tetrapeptides CVLS,
      CAIL and CQLS using a farnesyl transferase preparation from bovine brain. The
      data shows that the CQLS is a good acceptor of a farnesyl group similar to CVLS
      while it is a poor acceptor of a geranylgeranyl group unlike CAIL, which is a
      good acceptor of a geranylgeranyl group. This suggests that the CLN3 gene product
      may be a farnesylated protein.

PMID- 9151321
TI  - Different patterns of hydrophobic protein storage in different forms of neuronal
      ceroid lipofuscinosis (NCL, Batten disease).
AB  - Since the discovery of mitochondrial ATP synthase subunit c storage in different
      forms of neuronal ceroid lipofuscinosis (NCL, Batten disease), it has been found
      that other hydrophobic proteins also accumulate in different forms. Costorage of
      subunit c of vacuolar ATPase is observed in "mnd/mnd" mice and in English
      Setters, Border Collies and Tibetan Terriers. A small amount is stored in the
      ovine disease and none in the human late-infantile disease. It is a storage body
      matrix component. An additional 8 kDa component immunoreactive to vacuolar ATPase
      subunit c antibodies is found in brain-derived storage bodies. The sphingolipid
      activator proteins, SAPs A and D, are stored in the human infantile disease and a
      form in Miniature Schnauzer dogs, but neither of the c subunits are. These
      results suggest two classes of NCL, the subunit c-storing diseases, related by a
      series of lesions in a subunit c-turnover pathway, and the SAP-storing diseases.

PMID- 9151322
TI  - Sphingolipid activator proteins (SAPs) in neuronal ceroid lipofuscinoses (NCL).
AB  - Based on the predominant component of the storage material the neuronal ceroid
      lipofuscinoses (NCL) can be divided into two categories: one storing
      mitochondrial ATP synthase subunit c and the other storing sphingolipid activator
      proteins (SAPs). The latter group is represented by the human infantile NCL
      (INCL), a congenital ovine NCL, and a canine NCL. Small amounts of SAPs also
      accumulate in most other forms of NCL. The SAPs, their functions and occurrence
      in different forms of NCL, as well as the relationship between SAPs and palmitoyl
      protein thioesterase, an enzyme implicated in INCL, are discussed.

PMID- 9151323
TI  - Decreased lysosomal subunit c-degrading activity in fibroblasts from patients
      with late infantile neuronal ceroid lipofuscinosis.
AB  - We investigated in in-vitro cell-free incubation experiments which factor,
      lysosomal proteolytic dysfunction or structural alteration of subunit c, is
      responsible for the specific delay in the degradation of subunit c in patient
      cells with the late infantile form of neuronal ceroid lipofuscinosis. Experiments
      using substrates and soluble lysosomal fractions isolated separately from control
      and patient cells indicated that lysosomes from control cells are able to degrade
      mitochondrial subunit c either from control or patient cells at much faster rate
      than lysosomes from patient cells. Subunit c stored in patient cell lysosomes
      showed much more resistance to proteolytic attack than mitochondrial subunit c,
      suggesting that conformation of subunit c as well as lysosomal proteolytic
      dysfunction both participate in the specific lysosomal accumulation of subunit c
      in the late infantile disease.

PMID- 9151324
TI  - Light and electron microscopic studies on subunit c in cultured fibroblasts in
      late infantile and juvenile Batten disease.
AB  - Immunohistochemical and ultrastructural studies were undertaken to determine
      whether accumulation of subunit c of mitochondrial ATP synthase could be detected
      microscopically in fibroblasts cultured from patients with late infantile and
      with juvenile Batten disease. Cells were grown for five weeks with and without
      colchicine to inhibit cell division, and were studied grown on slides, as
      cytospin preparations or as centrifuged pellets. The two different
      immunohistochemical detection methods used (peroxidase/DAB and immunogoldsilver)
      gave different results, but neither method indicated any accumulation of subunit
      c. There was no ultrastructural or electronhistochemical evidence of storage. The
      published biochemical results which give apparently conflicting evidence of
      excess amounts of subunit c in cultured fibroblasts can be explained by
      quantitative differences and sensitivity of the detection methods.

PMID- 9151325
TI  - The ovine model of neuronal ceroid lipofuscinosis (NCL): its contribution to
      understanding the pathogenesis of Batten disease.
AB  - Development of the ovine model of NCL has been pivotal to our present
      understanding of the ceroid lipofuscinoses. Analyses of isolated storage product
      have shown it to be composed of identifiable chemical species of which subunit c
      of mitochondrial ATP synthase is dominant (ca 50%). It is an extremely
      hydrophobic protein and failure to catabolise it may be associated with a
      propensity to form paracrystalline structures with lipids that cannot be degraded
      by the normal complement of lysosomal enzymes. However, the putative biochemical
      defect must be related to it and may reside within the mitochondria. Multiple
      copies of subunit c help form the transmembrane Fo complex which, with partially
      immobilised lipids, forms an Fo complex domain. This may need to be disassembled
      in an orderly fashion before proteolysis of subunit c can occur. It is postulated
      that the primary defect may involve disassembly of the Fo complex domain which
      may involve more than one step.

PMID- 9151326
TI  - DNA diagnosis and identification of carriers of infantile and juvenile neuronal
      ceroid lipofuscinoses.
AB  - The recent identification of the genes and the mutations underlying infantile
      neuronal ceroid lipofuscinosis and juvenile onset neuronal ceroid lipofuscinosis
      facilitates specific DNA-based diagnostics for the disorders. We have developed a
      solid-phase minisequencing test for the identification of the major Finnish INCL
      mutation, an A to T transversion at nucleotide position 364 of the palmitoyl
      protein thioesterase gene on chromosome 1. This test has been applied for
      prenatal diagnosis and for identification of disease carriers in INCL families.
      For population-based screening for INCL carriers the coverage of the test would
      be 98%. In addition, by combining the solid-phase minisequencing test with whole
      genome preamplification, we have developed a procedure that allows reliable
      identification of the INCLFin-mutation in single blastomeres from in-vitro
      fertilized embryos. This method is applicable for preimplantation diagnosis, and
      thus it offers an alternative to early prenatal diagnosis in the prevention of
      INCL. A modification of the solid-phase minisequencing test was devised for
      detection of the major INCL mutation, a 1.02 kb deletion in the CLN3 gene on
      chromosome 16. The coverage of this test for diagnosis of INCL and identification
      of carriers is 90% in Finland and > 80% worldwide.

PMID- 9151327
TI  - Morphologic diagnosis in neuronal ceroid lipofuscinosis.
AB  - Morphologic pathology in NCL is marked by two processes, the interaction of which
      has not yet been completely clarified: 1) degeneration of nerve cells, foremost
      in the cerebral cortex, resulting in considerable cerebral atrophy in early
      childhood forms, likely responsible for clinical and neuroradiological findings;
      2) widespread accumulation of autofluorescent lysosomal lipopigments of varying
      ultrastructure, the demonstration of which is still largely responsible for
      diagnostic recognition of an individual patient's NCL. Numerous tissues and
      organs are available for biopsy, among them brain (historical), rectum (still
      favoured by some), skeletal muscle and peripheral nerves (largely by coincidence
      or "mistake"), skin and conjunctiva (the latter inferior to former in diagnostic
      yield) and, most easily retrievable, circulating lymphocytes. The distinct
      ultrastructure in the circulating lymphocytes permits a close
      cliniconeuropathological correlation which may only be surpassed by future
      genetic results. Diagnostic morphology of NCL variants and adult NCL, however, is
      still problematic, the former concerning autopsy studies of the brain, the latter
      concerning extracerebral biopsies.

PMID- 9151328
TI  - Neurophysiological findings in neuronal ceroid lipofuscinoses.

PMID- 9151329
TI  - Brain perfusion SPECT abnormalities in neuronal ceroid lipofuscinoses.
AB  - Brain perfusion was studied with the Tc-99m-HMPAO SPECT method in 19 INCL
      patients, 21 JNCL patients and 5 patients with Jansky-Bielschowsky variant
      disease (JBVD). The typical SPECT findings at an early stage of INCL were
      bilateral anterior frontal, posterior temporoparietal and occipital
      hypoperfusion, whereas reduction in cerebellar perfusion appeared later. However,
      perfusion of basal ganglia and thalami, although atrophic on MRI, was usually
      well preserved up to the terminal stage. All JNCL patients except one had at
      least one hypoperfused area. Mild hypoperfusion was usually located in the
      parietal and occipital lobes and cerebellum, whereas more severe hypoperfusion
      was observed in the temporal lobes. In JNCL, SPECT revealed lesions not detected
      on CT. All JBVD patients had supra- and infratentorial hypoperfusion, which was
      usually bilateral. This study shows that although in NCLs brain hypoperfusion can
      appear prior to structural abnormalities seen on MRI or CT, such abnormalities
      are not always associated with significant hypoperfusion.

PMID- 9151330
TI  - The value of positron emission tomography in the diagnosis and monitoring of late
      infantile and juvenile lipopigment storage disorders (so-called Batten or
      neuronal ceroid lipofuscinoses).
AB  - Positron Emission Tomography (PET) with 2-deoxy-2 [18F]-fluoro-D-glucose provides
      a measure of functional brain activity, particularly in the dendritic field. In
      CLN3 (juvenile neuronal ceroid lipofuscinosis or juvenile Batten disease, with
      fingerprint inclusions) hypometabolism slowly spreads from calcarine to anterior
      areas, sparing subcortical structures and brainstem. In CLN2 (late infantile
      neuronal ceroid lipofuscinosis or Jansky-Bielschowsky disease, with curvilinear
      inclusions) degeneration is rapid with generalized cortical and subcortical
      hypometabolism. This is associated with rapidly progressive cerebral atrophy on
      anatomical neuroimaging. A 4-year-old child with CLN2 scanned with PET 13 months
      after the clinical onset showed hypometabolism, severe in the thalamus and mild
      in cortical areas. Three other patients with CLN2 had severe generalized
      hypometabolism and brain atrophy. Longitudinal PET studies in CLN may provide key
      insights into degenerative processes.

PMID- 9151331
TI  - Lamotrigine therapy in infantile neuronal ceroid lipofuscinosis (INCL).
AB  - Since 1990, altogether 16 INCL patients received lamotrigine (LTG) because of
      intractable epilepsy. The response to LTG was favorable in 15/16 children. The
      severity of seizures decreased significantly in 15/16 patients, the frequency of
      seizures decreased in 14/16, and the effects were maintained. In addition, LTG
      had a beneficial effect on the well-being of 14/16 children. LTG failed to
      maintain it's efficacy in monotherapy. No severe side effects were found.

PMID- 9151332
TI  - Bone marrow transplantation in late infantile Batten disease and juvenile Batten
      disease.
AB  - Two patients, one each with LINCL and JNCL, underwent BMT in an attempt to alter
      the course of their disease. The LINCL patient received two transplants, one when
      asymptomatic, which was rapidly rejected, and a second BMT at age 3 years 9
      months when the EEG had become abnormal. He has deteriorated in the following 2
      years and now has only a few words, limited vision and feeding difficulties. Only
      two major seizures have occurred, but minor seizures are frequent. Although he is
      less severely affected than his sister at the same age, it is difficult to know
      if BMT has had any effect. The most significant difference is the relative
      mildness of seizure activity. The JNCL patient, transplanted at 8 years, when her
      visual problems had already started, is still in mainstream school, has good
      speech and good quality of life at age 9 1/2 years. No regression has been found,
      but EEG changes are now present and her vision has further deteriorated. The
      effect of BMT, if any, will not become apparent for several years in the more
      slowly progressive JNCL.

PMID- 9151333
TI  - In-utero and post-delivery supplementation of motor neuron degeneration mutant
      mice with polyunsaturated fatty acids does not alter the clinical or pathological
      course.
AB  - We have studied the effects of polyunsaturated fatty acid (PUFA) supplementation
      in utero and throughout life in mnd mutant mice, a proposed model for juvenile
      neuronal ceroid lipofuscinosis (CLN-3). Unlike our earlier in-vitro studies in
      humans with CLN-3, and in-vitro studies in CLN-3 lymphoblasts, we saw no
      beneficial effects in electroretinographic, electron microscopic or clinical
      studies in the mnd mice. Electron microscopy of brain revealed a pattern which
      was not consistent with the characteristic ceroid patterns in CLN-3. Our data
      suggest that the mnd mouse is not responsive to PUFA supplementation and may not
      be an appropriate animal model for CLN-3.

PMID- 9151334
TI  - Risk factors for latex hypersensitivity in childhood.
AB  - As hypersensitivity to natural rubber latex (NRL) has become an increasingly
      recognized problem in children, identification of all groups at risk seems
      important. In this study hypersensitivity to NRL was evaluated in 337 children
      with potential risk factors. We identified by questionnaire children's underlying
      diseases, history of surgical procedures, evidence of atopy and patient's history
      of NRL-specific reactions. Hypersensitivity to NRL and other allergens relevant
      in the Dusseldorf area was evaluated by skin prick test and specific IgE. In 9.2%
      of all children hypersensitivity to NRL was observed. Significant risk factors
      for hypersensitivity to NRL were, among the underlying diseases, spina bifida
      (odds ratio 29.2), hydrocephalus internus (10.1), gastrointestinal malformation
      (5.2) and atopy (2.2). Surgical procedures with significant risk were the
      implantation of a ventriculo-peritoneal shunt (15.7) and surgery of the
      gastrointestinal tract (3.1). Frequency of surgical procedures correlated (p <
      0.001) with risk of hypersensitivity. Frequent surgery and atopy were found to
      have an additional effect on the risk of hypersensitivity. Information about
      previous NRL-specific reactions obtained by questionnaire was of little
      predictive value when performing multivariate analysis. For children at high risk
      for hypersensitivity to NRL preoperative evaluation and, in case of
      hypersensitivity, preventive measures seem to be advised.

PMID- 9151335
TI  - Comparison of three immunoassays for diagnosing sensitization to latex in
      children with spina bifida.
AB  - As natural rubber latex (latex) has become more widespread in our environment,
      physicians have become increasingly aware of the problem of possible allergic
      reactions. Many fatal and near-fatal incidents have been reported (mainly during
      surgery) (1-3) and data has been published on groups frequently exposed to latex,
      such as patients with spina bifida (4-9), healthcare professionals (10-12) and
      occupationally exposed persons (13). The incidence of latex allergy in children
      seems to be increasing (14). Tests are therefore needed which can reliably detect
      sensitization to latex. Our aim was to compare the diagnostic accuracy of three
      commercial immunoassays for measuring specific IgE in serum to latex.

PMID- 9151336
TI  - The potential role of gastroesophageal reflux in the pathogenesis of food-induced
      wheezing.
AB  - Severe reactive airways disease (RAD) in children is frequently associated with
      gastroesophageal reflux or food allergy. However a relationship between these two
      confounding factors has yet to be investigated. We postulate that, in certain
      patients with micro-aspiration of gastric contents into the airways, food
      allergens sensitize T cells in the peribronchial lymphoid tissue and induce the
      production of food-specific IgE antibodies that sensitize airway cells.
      Subsequent exposure to these food allergens might then induce IgE dependent
      mediator release from mast cells as well as T cell and eosinophil activation,
      thus contributing to airway inflammation and RAD. In the current report, we
      describe the case of a patient with severe asthma who had food allergy and
      gastroesophageal reflux whose clinical findings support this hypothesis. We also
      provide additional evidence for a high rate of food sensitization in patients
      with bronchopulmonary dysplasia (BPD), RAD and GER. We conclude that additional
      studies are warranted to examine the possibility that patients who have RAD and
      GER require an evaluation for food allergy.

PMID- 9151337
TI  - Application of an electrophoretic methodology for the identification of low
      molecular weight proteins in foods.
AB  - Identification and characterisation of food proteins are core features of food
      allergy research. Current methods used to identify allergenic proteins in food
      have insufficient resolution and are unable to detect low molecular weight
      proteins. In this study we report the use of a simple SDS-PAGE method which
      allows resolution of small proteins. We have subsequently applied this method and
      reported presence of low molecular weight proteins in a range of hydrolysed milk
      formulae (Nutramigen, Pregistimil, Alfare, Pepti-Junior and Pregomin), and crude
      peanut protein extract. The molecular weight distribution for the peanut extract
      and the hydrolysates ranged between 5-200kDa and 2-17kDa respectively.

PMID- 9151338
TI  - CD4+ cells from patients with Common Variable Immunodeficiency have a reduced
      ability of CD40 ligand membrane expression after in vitro stimulation.
AB  - BACKGROUND: Common Variable Immunodeficiency (CVID) is characterized by defective
      antibody production. This has been variably attributed to intrinsic B-cell
      defects or to T-cell disfunctions. Recently, it has been reported that the
      expression of the CD40 Ligand (CD40L), a T-cell surface molecule that plays a
      critical role in the cell-contact-mediated helper signals provided to B-cells, is
      defective in a subset of patients with CVID. METHODS: To demonstrate that the
      defective expression is due to intrinsic functional abnormalities of CD4+
      lymphocytes, CD4+ cells were purified from eight patients with CVID and eight age
      paired controls, stimulated with PMA+Ionomycin, and studied for CD40L expression
      by flow cytometry using specific monoclonal antibodies. RESULTS AND CONCLUSIONS:
      The percentage of CD4+ cells expressing CD40L after optimal stimulation was
      correlated with age both in patients with CVID (r: 0.74; p: 0.04) and in healthy
      controls (r: 0.73; p: 0.04). The percentage of CD40L+ cells was reduced in
      patients with CVID compared to that of controls (p: 0.02 when data are paired for
      age) with a reduced density of expression (p: < 0.01). The defect was variable in
      different patients and in some cases it was marginal.

PMID- 9151339
TI  - Serum eosinophil cationic protein and interleukin-5 in children with bronchial
      asthma and acute bronchiolitis.
AB  - The aim of our study was to evaluate the clinical applicability of serum
      eosinophil cationic protein (ECP), interleukin-5 (IL-5) and total eosinophil
      counts in childhood asthma and bronchiolitis. These parameters were measured in
      44 children aged 12-84 months with moderate and mild asthma during symptomatic
      and asymptomatic phases of disease. Fifteen of the patients were included at the
      time of admission to hospital due to an acute asthmatic attack, and ten of these
      were also examined one month after discharge. None of the patients were treated
      with glucocorticoids or cromoglycate at any time during the study. Serum ECP was
      significantly increased in the children with acute asthma compared to children
      with stable moderate asthma, stable mild asthma, as well as to controls. There
      was no difference between the groups with stable asthma or between stable asthma
      and controls, and there was large overlap between all groups of asthmatics and
      controls. Detectable levels of circulating IL-5 were demonstrated in eight of 15
      children with acute asthma, with significantly higher levels in atopic children,
      whereas all samples from children with stable asthma and controls were negative.
      The results suggest that even though serum ECP and IL-5 increases during acute
      asthmatic attacks, these parameters cannot alone be used to discriminate between
      different groups of young children with stable asthma, nor between asthmatics and
      healthy controls. In addition, the same parameters of eosinophil inflammation
      were examined in serum samples from 25 children aged 1-17 months undergoing their
      first episode of acute bronchiolitis. Children with acute respiratory syncytial
      virus (RSV) bronchiolitis had significantly higher levels of serum ECP than those
      with RSV negative disease, whereas the total eosinophil counts were significantly
      decreased in all patients with acute bronchiolitis. Serum IL-5 was only detected
      in two children with acute bronchiolitis. The results suggest that the
      inflammation in RSV bronchiolitis differs from that induced by other viruses.

PMID- 9151340
TI  - Short stature in children with respiratory allergy.
AB  - We evaluated the prevalence of short stature (SS) among children with respiratory
      allergic disease followed up in a specialised centre. These patients (N = 617; 8
      months to 16 years) with respiratory allergy (asthma and/or rhinitis) were
      evaluated for SS (stature shorter than the 3rd percentile, NCHS pattern). The
      possible links between SS and gender; current age; type, severity, and duration
      of the allergic disease, treatment with corticosteroid and birth weight were also
      studied. To assess the influence of the socioeconomic level on SS frequency among
      atopics, 120 of these patients were compared to their non-atopics siblings. The
      overall prevalence of SS was 7.9%. Relationship between SS and gender type and
      severity of the allergic disease and treatment with corticosteroids were not
      observed. A significant higher frequency of SS occurred among patients with
      longer period of disease and birth weight less than 2,500 gr. Analysis of the
      pairs of brothers showed significant higher frequency of SS between allergics
      (12.5% x 4.2%) showing influence of allergic disease per se. Longitudinal studies
      for long periods of time are required to properly establish the relation between
      atopic disease and SS.

PMID- 9151341
TI  - Isolation of type 1 and type 2 cloned mite allergen-specific T cells from an
      asthmatic child.
AB  - Allergen-specific T cells have been thought to play a central role in the
      pathogenesis of asthma. It has been well documented that allergen-specific T
      cells derived from atopic patients are predominantly of type 2 T helper cell
      pattern. However, allergen-specific T cells derived in nonatopic normals are of
      type 1 in contrast to atopic patients. The purpose of the study was to develop
      and characterize both mite allergen-specific TH1 and TH2 clones from the same
      asthmatic child. With exogenous supplemental cytokine, both TH1 and TH2 clones
      from the same patient have been developed and maintained in this laboratory for
      more than one year. All these T cell clones showed dose dependent allergen
      specific proliferative response and expressed with CD4+, CD45RA- markers.
      Elucidation of the origin and interaction between these two different types of T
      helper cells might shed light on understanding the pathogenesis of atopic
      diseases and the mechanisms of hyposensitization in atopic patients.

PMID- 9151342
TI  - Monoclonal antibody therapy of inflammatory bowel disease.
AB  - Animal models of inflammatory bowel disease have provided insight in the
      regulation of mucosal inflammation. This has resulted in novel therapeutic
      approaches that specifically target a single inflammatory mediator. Monoclonal
      antibody therapy has been used in steroid refractory Crohn's disease patients.
      Anti-TNF antibody administration induced complete remissions and few side effects
      were observed. Although these findings need to be confirmed in controlled and
      long term treatment studies they may guide the development of specific and
      effective therapies for these diseases.

PMID- 9151343
TI  - Antiepileptic drug treatment in the nineties in The Netherlands.
AB  - In this review the 'state of the art' of treating patients with epilepsy in the
      nineties in the Netherlands is presented. It describes general strategies for
      treatment with antiepileptic drugs and the history of development of the
      classical anticonvulsant drugs. Eight new drugs, including vigabatrin,
      lamotrigine, felbamate, oxcarbazepine, gabapentin, tiagabine, levetiracetam and
      topiramate are discussed. A review of their pharmacological and clinical
      properties is presented. Dutch experience with these drugs is included.

PMID- 9151344
TI  - Are SSRIs true antidepressant drugs? A plea for the re-evaluation of their
      therapeutic potential and safety.

PMID- 9151345
TI  - Pharmacoeconomics: where is the link with pharmacokinetics and biopharmaceutics?
AB  - Several, mainly macroeconomic factors are putting increasing pressure on health
      care budgets. These budget constraints lead to cost containment measures by all
      partners involved in health care. Pharmacotherapy, too, is facing an increasing
      involvement in health economics or outcomes research. This paper will first deal
      with some basic principles of pharmacoeconomics. The relationship with
      pharmacokinetics and biopharmaceutics has perhaps not yet been an issue as such,
      though it should be pointed out that they play a key role in the efficiency of
      drug use. Many of the basic R&D investments aimed at developing cost-effective
      medicines should be founded on adequate pharmacokinetics. Also a rational use of
      drugs in practice can be achieved by adequate drug monitoring, resulting in a
      gain in cost-effectiveness. Last but not least, pharmacokinetics and
      biopharmaceutics can offer opportunities for the rational use of new or existing
      pharmaceutical products and for the maintenance of a sufficient market share.
      Some of these more technical aspects are discussed in the second part of this
      presentation.

PMID- 9151346
TI  - Lifestyle, fibrinolysis and lipids.
AB  - Lifestyle including eating habits, physical training, smoking, drinking alcoholic
      beverages etc. can to a certain extent maintain or spoil our health. The
      physiological mechanisms of haemostasis and of lipoprotein metabolism play a role
      in acute cardiovascular diseases but also in a great number of chronic diseases
      in which vascular pathology is prominent. Imparied fibrinolysis and increased
      lipid levels are often incriminated in vascular disease. Lifestyle can modify
      fibrinolysis as well as lipid levels. Physical training, moderate eating habits,
      no smoking, moderate alcohol intake will be a beneficial influence on both
      fibrinolysis and lipid levels. The possibility that long-term pharmacological
      intervention may adversely affect fibrinolysis and lipid levels should always be
      considered.

PMID- 9151347
TI  - The anaesthetist as determinant factor of quality of surgical antimicrobial
      prophylaxis. A survey in a university hospital.
AB  - In actual surgical antimicrobial prophylaxis, the anaesthetist administers the
      drugs at induction of anaesthesia. In the first phase of our quality-of-use
      intervention study on antimicrobial drugs in a large university hospital,
      information on the practice of antimicrobial prophylaxis was needed. The staff of
      44 anaesthetists was interviewed by means of a questionnaire. Response rate was
      36/44 (82%). The anaesthetists' method of administering surgical prophylaxis was
      rather uniform and inexpensive: cephalosporins were almost exclusively
      administered by bolus method. The main reason was that infusion was more
      cumbersome (range 77-85%). Communication between surgeon and anaesthetist was
      reported to be poor, and in two out of three operating departments, orders of
      prophylaxis transmitted at or after induction accounted for more than 80%.
      Seventy-seven percent of the responders asked the surgeon if prophylaxis was
      necessary if they were in doubt; 20% responded that they checked it
      systematically. The data collected by the inquiry proved useful in the process of
      optimizing surgical prophylaxis in our hospital.

PMID- 9151348
TI  - Consumption of anti-infective drugs in Bulgaria for the period from 1979 to 1994.
AB  - The use of systemic antibacterial drugs in Bulgaria for the period from 1979 to
      1994 had been studied using the Defined Daily Doses (DDD) methodology. The total
      consumption of antibacterials, the consumption by therapeutic groups and
      preparations were presented. The usage of anti-infectives in Bulgaria was growing
      during the period under discussion. Most of the groups followed the general
      tendency of the total consumption showing their own variations throughout the
      years. The role of the different preparations was defined. Bulgarians' way of
      using antibacterials showed the following characteristics: permanent increase in
      the total consumption; high consumption of tetracyclines and extended spectrum
      penicillins; low consumption of narrow spectrum antibiotics; and relatively high
      consumption of aminoglycosides and chloramphenicol. In this study an attempt was
      made to relate the data with several factors influencing the consumption. For
      comparison we studied available statistical data of some other countries.

PMID- 9151349
TI  - Patient-oriented pharmacy on a special ward: results of a pilot project in
      Germany.
AB  - In Germany a pilot project in patient-oriented pharmacy has been started in the
      Berufsgenossenschaftliche Unfallklinik Ludwigshafen to demonstrate the efficiency
      of this modem way of practising pharmacy in hospital. A special ward of the
      orthopaedic department (spinal injuries, 25 beds) was chosen for this project.
      Since February 1st, 1994, the pharmacists have taken over the stock management on
      the ward and dispense oral drugs in unit-dose systems for each patient. The
      pharmacists participate also in ward rounds and check the patients' medication
      charts in order to support and inform the physicians. So the project is a
      combination of improved patient care and an advisory service in pharmaceutical
      questions for the medical staff. In the first year of this project, which is
      still ongoing (February 1994-January 1995), 123 patients were treated on the
      ward; the average duration of stay was about 77 days. During this first year the
      pharmacists registered 111 questions and events leading to pharmaceutical
      interventions. The most important results of the project are the improvement in
      drug safety and more effective drug use. Other positive results are: during the
      course of the project the cooperation between the medical and pharmaceutical
      staff has been improved and the drug management by the pharmacy has resulted in a
      17 per cent reduction of medication costs in comparison to the year before. All
      these results clearly demonstrate the success of these first steps in patient
      oriented pharmacy.

PMID- 9151351
TI  - Interaction between the Drug Information Centre and the Regional Centre for
      Adverse Drug Reaction Monitoring in northern Sweden.

PMID- 9151350
TI  - An evaluation of community pharmacy records in the development of pharmaceutical
      care in The Netherlands.
AB  - An electronic patient database linking prescribes with a Dutch community pharmacy
      consortium was evaluated in a subset of the population of Noordwijk (11,760
      patients out of a total of 25,600). The pharmacy database (a file of 41 disease
      contra-indications representing a subset of the prescribers' medical diagnosis)
      was studied in order to assess its value for the accurate discrimination of
      target patient groups within the community and for support to the pharmaceutical
      care of individual patients. The aim was to examine the application of the
      pharmacy records to pharmaceutical care, tested by measuring the accuracy of the
      pharmacy database to predict the community public health profile; and, more
      specifically, the accuracy to identify three potential target groups for
      pharmaceutical care. The records of patients with angina, chronic respiratory
      disease and diabetes (n = 1116), representing 65% of the total pharmacy morbidity
      records, were studied in detail and verified by the files and texts of the
      prescriber's individual patient records. From samples of patients (n = 273) from
      the three patient groups, the extent and nature of co-morbidity, polypharmacy
      (drug entities prescribed annually) and drug therapy instability (prescription
      changes to dose or dose form annually) were characterised. Angina patients showed
      the most comorbidity, 46% having three or more additional diseases; chronic
      respiratory disease patients showed most drug therapy instability; and insulin
      dependent diabetic patients received most polypharmacy per disease. The pharmacy
      database predicted the prevalence of 10 of 23 relevant disease categories
      (representing 51% of the total morbidity on the medical records). However, the
      prevalences of eight categories were underestimated and of five categories
      overestimated. Of the three patient groups, 73% of patients appeared on both the
      pharmacy and the medical database. Of the total co-morbidity recorded for these
      patients, 68% of records were common to both databases. The database
      discrepancies (32%) were due to morbidity omitted (12%) and morbidity unverified
      (10%) on the pharmacy database, together with morbidity omitted from the medical
      database (10%). The current pharmacy database provides a limited view of
      morbidity. A strategic approach to pharmaceutical care requires pharmacists and
      prescribers to verify and share patient information if patient groups and
      individuals within a group are to be usefully targeted.

PMID- 9151352
TI  - Noise stress does not modulate effects of smoking/nicotine on beta-endorphin,
      cortisol, ACTH, glucose, and mood.
AB  - Noise-dependent effects of smoking multiple cigarettes on subjective state and
      blood concentrations of ACTH, beta-endorphin, cortisol, and glucose were assessed
      in a repeated measures design where noise level (high versus minimal) was crossed
      with nicotine dose (quasi-ad lib own brand versus 1.0 mg FTC nicotine machine
      delivered dose versus 0.05 mg FTC nicotine machine-delivered dose). Cortisol and
      ACTH were increased by nicotine, but not by noise and there was no noise by dose
      interaction. In contrast, nicotine did not increase beta-endorphin in either
      noise condition and there was no dose by noise interaction for beta-endorphin.
      However, noise was associated with a modest increase in beta-endorphin. The
      effects of nicotine on blood glucose varied as a function of the number of
      cigarettes smoked. However, the effects of nicotine on glucose, hormones, and
      subjective state did not vary as a function of noise stress.

PMID- 9151353
TI  - Acquisition of cocaine self-administration after social stress: role of accumbens
      dopamine.
AB  - Exposure to either aversive or rewarding environmental stimuli increases
      extracellular dopamine (DA) concentrations in terminal areas of the
      mesocorticolimbic dopamine system. Furthermore, behavioral reactivity to an
      environmental stressor has been shown to correlate with latency to initiate self
      administration of psychomotor stimulant drugs. The present study examined the
      behavioral and dopaminergic responses of rats to social defeat stress and
      compared latencies to initiate cocaine self-administration in defeated and non
      defeated rats. In vivo microdialysis was used to examine the effects of social
      defeat stress on DA concentrations in nucleus accumbens of freely-moving rats.
      During the experimental session, dialysate and video recording samples were
      collected from previously-defeated and non-defeated "intruder" rats in
      consecutive phases, while (1) in the home cage, (2) when placed in the empty,
      soiled cage of a resident rat which had previously defeated them, and (3) when
      exposed to threat of defeat by the resident. Immediately following threat of
      defeat, previously-defeated and non-defeated intruders were given the opportunity
      to self-administer cocaine IV. When exposed to the olfactory cues of an
      aggressive resident, extracellular DA levels in nucleus accumbens increased to
      approximately 135% of baseline in previously defeated rats versus 125% of
      baseline in non-defeated rats. When exposed to social threat by the resident, DA
      levels further increased to 145% of baseline in previously defeated rats versus
      120% in non-defeated rats. Previously defeated rats acquired cocaine self
      administration in approximately half the time of non-defeated rats, consistent
      with the hypothesis that prior stress exposure may induce a cross-sensitization
      to the rewarding effects of cocaine. These results are consistent with the idea
      that exposure to stress may induce changes in central dopaminergic activity,
      which may render an individual more vulnerable to acquiring psychomotor stimulant
      self-administration.

PMID- 9151354
TI  - Cocaine impairs acquisition of an autoshaped lever-touch response.
AB  - The effects of daily peripheral (IP) post-session injection of cocaine on the
      development of an autoshaped lever-touch response in rats were investigated. Male
      Sprague-Dawley rats received ten daily pairings of a retractable lever
      (conditioned stimulus; CS) and food delivery (unconditioned stimulus; UCS). Food
      delivery occurred if the subjects contacted the extended lever within 10 s, or,
      if the subjects failed to contact the lever, at the end of the 10-s stimulus
      interval. These contingencies resulted in increased lever-touch responses over 10
      days of conditioning. Cocaine (5.6-19.0 mg/kg) impaired development of the lever
      touch response, as compared to saline-treated control subjects. Because the
      injections were given immediately after each conditioning session, we suggest
      that cocaine affects the neural processes involved in consolidation. Three
      additional control experiments support this suggestion. The effect of cocaine on
      lever-touch acquisition was time-dependent as daily injection of cocaine (5.6
      mg/kg) 3 h after each conditioning session did not affect lever-touch
      acquisition. In addition, the effect of cocaine was dependent upon the explicit
      pairing of lever extension (CS) and food delivery (UCS) as immediate post-session
      cocaine (5.6 mg/kg) administration did not alter responding when the presentation
      of both the CS and the UCS was uncorrelated. Cocaine (5.6 mg/kg) administered to
      subjects previously trained to a performance criterion did not affect lever-touch
      responding, indicating that cocaine administration (5.6 mg/kg) impairs the
      development, but not the maintenance, of autoshaped lever-touch responding. In
      contrast, the highest dose of cocaine tested, 19.0 mg/kg, did decrease lever
      touch responding in well-trained subjects, indicating that post-session
      administration of higher doses of cocaine can produce aversive effects that may
      affect both the acquisition and maintenance of appetitively motivated behavior in
      the rat. The relative contributions of the instrumental and classical
      associations inherent in the autoshaping procedure were investigated by altering
      response contingencies. Rats showed no evidence of learning the lever-touch
      response when lever insertion and food delivery were positively correlated, and
      no explicit response contingency was present (classical conditioning); further,
      cocaine-treated subjects did not differ from saline-treated subjects. However,
      cocaine did impair lever-touch responding in the instrumental version of the
      task. Taken together, these results show that the post-session administration of
      cocaine can impair the acquisition of a multi-trial, multi-session appetitively
      motivated response.

PMID- 9151355
TI  - Ethanol effects on self-administration of alfentanil, cocaine, and nomifensine in
      rhesus monkeys.
AB  - A common form of polydrug use is that of cocaine and ethanol. The identification
      of an ethanol-cocaine combination product, cocaethylene, with properties in
      common with cocaine, has led to speculation that this metabolite may contribute
      to the co-abuse of cocaine and ethanol. In order to determine whether ethanol
      pretreatments selectively altered cocaine's reinforcing potency, ethanol
      pretreatments were given to monkeys trained to press levers and receive IV
      infusions of several doses of cocaine or alfentanil. In addition, nomifensine, a
      drug which has a mechanism of action similar to cocaine's, was evaluated in the
      presence and absence of ethanol in monkeys with the cocaine baseline history.
      Ethanol, in doses ranging from 100 to 1780 mg/kg, given 10 min before the 130-min
      session, had no effect on responding maintained by alfentanil. These doses also
      had no significant effect on cocaine-maintained responding, although the potency
      of cocaine as a reinforcer was increased following administration of 1000 mg/kg
      ethanol in two of the four subjects. The potency of nomifensine as a reinforcer
      was significantly increased by 1000 mg/kg ethanol, but again, this enhancement
      was limited to the same two subjects. These data indicate that, in this paradigm,
      cocaethylene did not selectively modify cocaine's reinforcing potency, but there
      appear to be individual differences with respect to ethanol's ability to
      stimulate rates of drug-maintained responding.

PMID- 9151356
TI  - Evidence that the median raphe nucleus--dorsal hippocampal pathway mediates
      diazepam withdrawal-induced anxiety.
AB  - On the basis of our previous series of experiments we had postulated that the
      increased anxiety that occurred during diazepam withdrawal was mediated by
      increased 5-HT release in the hippocampus. The present series of experiments
      provide evidence for a major role of the median raphe nucleus (MRN) dorsal
      hippocampal pathway. Rats were treated once daily for 21 days with diazepam (2
      mg/kg IP) and then tested after 24 h withdrawal in the social interaction test of
      anxiety. Relative to chronically vehicle treated animals, those withdrawn from
      diazepam were significantly more anxious and had significantly greater K(+)
      evoked release of [3H]-5-hydroxytryptamine (5-HT) from slices of dorsal and of
      ventral regions of the hippocampus. Estimation of extracellular concentrations of
      5-HT within the dorsal hippocampus, using in-vivo microdialysis, showed doubling
      in the levels of 5-HT in the rats withdrawn from chronic diazepam treatment. This
      just failed to reach significance, but 33% of the rats showed dramatic increases
      (650%). It was not possible to test these animals in the social interaction test,
      but it is proposed that only the diazepam-withdrawn rats with raised
      extracellular levels of 5-HT would have displayed increased anxiety. 5-HT1A
      receptor agonists injected into the MRN decrease the MRN firing rate, and hence
      the release of 5-HT in the dorsal hippocampus. As a further test of our
      hypothesis, we examined the effects of MRN injection of the 5-HT1A receptor
      agonist, 8-OH DPAT, on animals withdrawn from diazepam and tested in the low
      light familiar condition of the social interaction test. 8-OH DPAT (50-200 ng)
      dose-dependently reversed the anxiogenic effect of diazepam withdrawal, while
      having no effects in chronic vehicle-treated animals. These results provide clear
      evidence that the MRN-dorsal hippocampal 5-HT pathway is at least one of the
      pathways playing an important role in mediating diazepam withdrawal-induced
      anxiety.

PMID- 9151357
TI  - Increased cyclic AMP response to forskolin in Epstein-Barr virus-transformed
      human B-lymphocytes derived from schizophrenics.
AB  - Phorbol 12-myristate-13-acetate (PMA), a protein kinase C (PKC) activator,
      elevated basal cyclic AMP levels and enhanced isoproterenol-, prostaglandin E1-
      (PGE1), forskolin- and cholera toxin-stimulated cyclic AMP accumulation in
      Epstein-Barr virus (EBV)-transformed human B-lymphocytes. Staurosporine, a PKC
      inhibitor, significantly antagonized the increase in cyclic AMP accumulation
      produced by PMA, whereas the inactive phorbol ester, 4 alpha-phorbol 12,13
      didecanoate (4 alpha PDD), had no effect. Basal levels of cyclic AMP and the
      accumulation of cyclic AMP produced by PMA, isoproterenol, PGE1, cholera toxin
      and the combination of these compounds with PMA were not significantly different
      between schizophrenics and controls. The cyclic AMP response to forskolin in the
      presence and absence of PMA was significantly greater in EBV-transformed human B
      lymphocytes from schizophrenics. These results suggest that activation of
      adenylyl cyclase by forskolin is elevated in EBV-transformed B-lymphocytes
      derived from schizophrenics and that this elevation is further enhanced through a
      PKC-dependent phosphorylation mechanism.

PMID- 9151358
TI  - 5-HT3 receptor mediated dopamine release in the nucleus accumbens during
      withdrawal from continuous cocaine.
AB  - The present experiment examined changes in the ability of the selective 5-HT3
      receptor agonist, 1-(m-chlorophenyl)-biguanide (mCPBG), to facilitate K(+)
      induced dopamine (DA) release during withdrawal from continuous cocaine
      administration. Rats were withdrawn from continuous cocaine administration (40
      mg/kg per day cocaine for 14 days) for 7 days, and then slices from the nucleus
      accumbens obtained. Following an equilibration period, the slices were perfused
      with 0, 12.5, 25, or 50 microM mCPBG in the absence and presence of 25 mM K+. The
      samples were assayed for DA content by HPLC with electrochemical detection.
      Continuous cocaine administration significantly attenuated the ability of mCPBG
      to facilitate K(+)-induced DA overflow compared to saline control rats. These
      results suggest that continuous cocaine administration functionally down
      regulates 5-HT3 receptors in the nucleus accumbens. These results further suggest
      that 5-HT3 receptor subsensitivity may represent a partial mechanism for the
      tolerance induced by continuous cocaine administration.

PMID- 9151359
TI  - Subchronic effects of clozapine and haloperidol on rats' forelimb force and
      duration during a press-while-licking task.
AB  - In order to compare and contrast the behavioral effects of the typical
      neuroleptic haloperidol with the atypical neuroleptic clozapine, ten daily doses
      of these drugs were administered to separate groups of rats trained to extend the
      forelimb through a rectangular hole and to exert downward pressure on a force
      transducer to gain access to water. Doses were individually titrated daily for
      each rat in an attempt to achieve a 50% reduction in time on task (analogous to
      response rate) during 8-min daily sessions. Clozapine-treated rats exhibited
      dramatic tolerance to the drug's suppressive effect on time on task. In contrast,
      haloperidol rats displayed little tolerance on this measure. Despite the
      tolerance reflected by time on task, no tolerance was seen in clozapine's marked
      slowing of the dominant frequency of oscillations in forelimb force as measured
      by Fourier analysis of the force-time recordings. Haloperidol did not slow the
      dominant frequency. No tolerance was seen for clozapine's effects on forelimb
      force or tremor measures. Haloperidol did not significantly affect forelimb
      force. Both haloperidol and clozapine produced increases in the duration of long
      duration forelimb responses, and no tolerance was seen for either drug on this
      measure of behavior. For clozapine, the dissociation between the tendency to
      respond (time on task) and the observed slowing of the dominant frequency may
      reflect effects peculiar to atypical neuroleptics, while the lengthening of long
      duration responses by both drugs may reflect a more general behavioral effect
      that is characteristic of both typical and atypical antipsychotic drugs.

PMID- 9151360
TI  - Effects of haloperidol on sensory processing in the hippocampus during classical
      eyeblink conditioning.
AB  - The rabbit classical eyeblink conditioning paradigm was used to assess the
      effects of haloperidol on hippocampal function. Haloperidol disrupted hippocampal
      activity and conditioned responses (CRs) at low but not high conditioned stimulus
      (CS) intensities. The observed relationship of hippocampal activity and the CR
      suggested that the hippocampus encoded sensory features associated with the
      learned response. Sensory processing by the hippocampus appeared to be altered by
      haloperidol through attenuation of the ability of a CS to evoke a learned
      response. Results are discussed in terms of the role of the hippocampus in
      sensory processing and possible mechanisms for the beneficial effects of
      haloperidol in schizophrenia. Classical eyeblink conditioning may provide a model
      system for studying behavioral and biological issues relevant to the etiology and
      treatment of schizophrenia.

PMID- 9151361
TI  - Inhibition of 5-HT cell firing in the DRN by non-selective 5-HT reuptake
      inhibitors: studies on the role of 5-HT1A autoreceptors and noradrenergic
      mechanisms.
AB  - Improved clinical antidepressant efficacy may result if the acute inhibition of 5
      HT cell firing induced by antidepressants is prevented. Here we examined whether
      inhibition of 5-HT cell firing by non-selective 5-HT uptake inhibiting
      antidepressant drugs is reversed by a selective 5-HT1A receptor antagonist. In
      addition, we examined whether concomitant blockade of NA uptake offsets the
      inhibition of 5-HT cell firing resulting from 5-HT uptake blockade.
      Antidepressants which block 5-HT uptake (paroxetine, clomipramine, amitriptyline,
      venlafaxine), all caused dose-dependent and complete inhibition of 5-HT cell
      firing. Desipramine, a selective NA uptake blocker, caused a slight reduction in
      firing. The selective 5-HT1A receptor antagonist, WAY 100635, reversed the
      inhibition of 5-HT cell firing induced by clomipramine, amitriptyline,
      venlafaxine, and paroxetine, but not that induced by the alpha 1 adrenoceptor
      antagonist, prazosin. Desipramine, at a dose which increased extracellular NA in
      the DRN, reversed the effect of prazosin but did not alter the ability of
      paroxetine to inhibit 5-HT cell firing. Our data indicate that antidepressant
      drugs with 5-HT uptake blocking properties inhibit 5-HT cell firing via
      activation of 5-HT1A autoreceptors, and do so irrespective of their effects on NA
      uptake. These data are discussed in relation to the application of 5-HT1A
      receptor antagonists to enhance the clinical efficacy of antidepressant drugs.

PMID- 9151362
TI  - Antidepressant treatment in helpless rats: effect on the electrophysiological
      activity of raphe dorsalis serotonergic neurons.
AB  - Chronic treatment with antidepressants renders serotonergic neuronal firing less
      sensitive to the inhibitory effect of serotonin (5-HT) reuptake blockers in the
      rat, and this has been considered as a major correlate of the therapeutic action
      of these drugs. We investigated whether the same mechanisms could be evidenced in
      an experimental model of depression, the learned helplessness paradigm. Rats
      rendered helpless by a single session of inescapable electrical footshocks
      exhibit, for several days, depression-like behavioural deficits which can be
      reversed by sub-chronic, but not acute, treatment with antidepressants. Recording
      of serotonergic neurons in the dorsal raphe nucleus revealed that, under baseline
      conditions, the spontaneous firing was similar in helpless rats and in non
      helpless controls. However, neurons in the former group exhibited an enhanced
      sensitivity to the inhibitory action of the 5-HT reuptake blocker, citalopram
      (ED50 = 0.18 +/- 0.02 mg/kg IV in helpless rats versus 0.27 +/- 0.03 mg/kg IV in
      controls, P < 0.05). Treatment with zimeldine during 3 consecutive days induced
      in both helpless and control rats, a decrease in the inhibitory response of
      serotonergic neurons to the citalopram challenge, which resulted in a
      normalization of the neuronal reactivity in the helpless group (ED50 = 0.31 +/-
      0.03 mg/kg IV). Since this adaptive phenomenon parallels the behavioural
      improvement induced by the repeated administration of zimeldine and other
      antidepressants in helpless rats, it might be considered as a crucial event in
      the mechanism of therapeutic action of these drugs.

PMID- 9151363
TI  - Improvement in accuracy of delayed recall in aged and non-aged, mature monkeys
      after intramuscular or transdermal administration of the CNS nicotinic receptor
      agonist ABT-418.
AB  - ABT-418 was evaluated for its ability to enhance accuracy on a delayed matching
      to-sample (DMTS) task by aged monkeys following intramuscular administration, and
      in non-aged mature monkeys following transdermal application. Aged monkeys were
      impaired in their performance of the DMTS task such that the longest delay
      intervals performed at above-chance levels extended only to 20 s. In contrast,
      for non-aged, mature animals, delay intervals extended to 140 s. In aged monkeys,
      the response to ABT-418 was highly individualized with animals responding to one
      or more doses in the range of 2-259 nmol/kg. A systematic dose-dependent
      enhancement of DMTS accuracy was not observed. When the individualized "best
      dose" was administered on a separate occasion, overall DMTS accuracy was
      increased by 12.6%. By 24 h after administration, accuracy was at control levels.
      In young monkeys, a significant dose-dependent enhancement of DMTS performance
      (an overall increase of 11.25% above baseline accuracy) was observed 5 h after
      application of a transdermal patch designed to maintain steady-state plasma
      levels of ABT-418 of 40-60 ng/ml over a 24-h period. Again there was some
      individual responsiveness to one of the three doses. When data included only the
      individualized best doses of ABT-418 for each animal, a similar enhancement of
      accuracy was observed for both the 5-h and 24-h test intervals. In neither the
      aged nor the young cohorts was enhancement of performance associated with altered
      response latencies or with any overt side effects of ABT-418. Thus, these data
      are consistent with the ability of ABT-418 to improve DMTS performance in both
      young and aged monkeys. In aged monkeys, this response was observed only after
      administration of individualized optimal doses for different monkeys. In young
      monkeys, a more systematic enhancement of DMTS accuracy was observed. Further,
      transdermal delivery of ABT-418 in non-aged monkeys demonstrated prolonged
      performance enhancement compared with IM injection to at least 24 h after patch
      administration.

PMID- 9151364
TI  - The GABAA agonist THIP produces slow wave sleep and reduces spindling activity in
      NREM sleep in humans.
AB  - Recent studies in the rat demonstrated that systemic administration of muscimol
      and THIP, both selective GABAA receptor agonists, elevates slow wave activity in
      the EEG during non-rapid eye movement (NREM) sleep. In this placebo-controlled
      study, we assessed the influence of an oral dose of 20 mg THIP on nocturnal sleep
      in young healthy humans. Compared to placebo, THIP increased slow wave sleep by
      about 25 min. Spectral analysis of the EEG within NREM sleep revealed significant
      elevations in the lower frequencies (< 8 Hz) and reductions in the spindle
      frequency range (approximately 10-16 Hz). In accordance with previous findings in
      the rat, these data imply that GABAA agonists promote deep NREM sleep, without
      suppressing REM sleep. These effects are opposite to those induced by agonistic
      modulators of GABAA receptors such as benzodiazepines and are at variance with
      established mechanisms according to which GABAA agonists and modulatory agonists
      would have similar effects. The sleep response to GABAA agonists is highly
      similar to that evoked by sustained wakefulness, suggesting that GABAA receptors
      may be implicated in the homeostatic regulation of sleep.

PMID- 9151365
TI  - Discriminative stimulus effects of buprenorphine in the rat.
AB  - Buprenorphine, a potent "low efficacy" or "partial" morphine-like opioid agonist,
      has morphine-like discriminative effects in animals and humans discriminating
      morphine or a related drug. The purpose of the present study was to characterize
      further the discriminative effects of buprenorphine in subjects trained to
      discriminate buprenorphine itself. Rats trained to discriminate between SC
      injections of saline and either 0.03 or 0.1 mg/kg buprenorphine generalized
      completely to morphine and to other morphine-like agonists. These drugs were
      approximately 3 times more potent in the rats trained with 0.03 mg/kg
      buprenorphine than in those trained with 0.1 mg/kg; however, the potency of
      buprenorphine itself did not differ significantly between groups. Indicative of
      efficacy differences among mixed-action opioids, rats discriminating 0.03 mg/kg
      buprenorphine generalized completely to butorphanol and pentazocine and partially
      to nalbuphine, whereas those discriminating 0.1 mg/kg generalized completely to
      butorphanol, partially to pentazocine, and little to nalbuphine. Stimulus control
      of behavior by 0.1 mg/kg buprenorphine was blocked surmountably by low doses of
      antagonists, stereoselective, and pharmacologically selective. These results are
      consistent with those of other studies showing that the discriminative effects of
      buprenorphine are morphine-like and mediated by the mu-opioid receptor, and
      extend the conditions under which this has been demonstrated to stimulus control
      maintained by buprenorphine itself.

PMID- 9151366
TI  - Risperidone-induced galactorrhea.

PMID- 9151367
TI  - The role of nitric oxide in respiratory disease.
AB  - Nitric oxide (NO) is found in both the upper and lower airways of man. In the
      lower airways it is found at concentrations less than 3 ppb, and in the upper
      airways at about 400 ppb. The NO found in the upper airways is thought to play a
      role in maintaining the sterility of the paranasal sinuses. NO is also produced
      by the endothelium of the pulmonary vasculature. Endothelium-derived NO is a
      potent vasodilator involved in maintaining low pulmonary tone. Impaired
      endothelial NO production is thought to be involved in some types of pulmonary
      hypertension. When inhaled, NO acts as a selective pulmonary vasodilator which is
      used to treat respiratory diseases. One area in which NO has proven to be
      particularly effective is in the treatment of persistent pulmonary hypertension
      of the newborn. Inhaled NO therapy can be used in the treatment of adult
      respiratory distress syndrome, primary pulmonary hypertension and chronic
      obstructive pulmonary disease.

PMID- 9151368
TI  - Skin and bones: dermatologic conditions with skeletal abnormalities.
AB  - OBJECTIVE: Radiologists should be aware of the fact that many dermatologic
      conditions have associated skeletal abnormalities. This pictorial essay seeks to
      acquaint radiologists with these associations. DESIGN: Twenty-four skin and bone
      conditions are portrayed and discussed under the headings of: disorders of the
      epidermis, disorders of the dermis, disorders of the sebaceous glands, disorders
      of pigmentation, disorders of the nails, tumors, the phakomatoses, immunologic
      allergic disorders, and infections. In addition, a table is provided as an
      expanded listing of conditions with such associations. CONCLUSION: This pictorial
      essay will help radiologists and other practitioners become familiar with
      dermatologic conditions that have associated skeletal abnormalities.

PMID- 9151369
TI  - Microscopic intraosseous extension of osteosarcoma: assessment on dynamic
      contrast-enhanced MRI.
AB  - OBJECTIVE: This study investigated whether dynamic MRI could determine
      microscopic intraosseous invasion in osteosarcoma. PATIENTS: Six patients with
      osteosarcoma who underwent total resection of the tumor after chemotherapy were
      studied. DESIGN: The steepest slope value of the time-intensity curve was
      calculated on the basis of the first-pass method on dynamic MRI performed after
      chemotherapy. Slope value modified log = [100.(SIb - SIa)/(Tb - Ta)/SIa], where
      SIa and SIb represent the signal intensity at time points Ta and Tb when the
      steepest slope started and ended, respectively. The slope value was correlated
      with the histological findings of the surgical specimens. The findings on
      conventional MRI were also reviewed. RESULTS AND CONCLUSIONS: In five of six
      patients microscopic tumor invasion ranging from 1 to 3.5 cm in depth was
      pathologically proven. The slope value within the microscopic invasion (-0.052 +/
      0.267) was significantly greater than that of tumour-free marrow (-0.609 +/-
      0.220) and less than that in areas showing macroscopic tumor invasion (0.595 +/-
      0.483) (P < 0.001). Histological examination disclosed the dilatation of small
      vessels within the macroscopic and microscopic invasion. Findings on conventional
      MRI varied among patients; microscopic invasion was not detected in one,
      underestimated in two, and overestimated in two. It is concluded that calculation
      of the slope value on dynamic MRI can discriminate regions of microscopic
      invasion from tumor-free marrow in patients with osteosarcoma after chemotherapy.

PMID- 9151370
TI  - The prevalence of diffuse idiopathic skeletal hyperostosis (DISH) in two large
      American Midwest metropolitan hospital populations.
AB  - OBJECTIVE: There are no published large-scale studies of the overall prevalence
      of diffuse idiopathic skeletal hyperostosis (DISH) and it has been proposed that
      the prevalence is greater than previously reported. We thus decided to review
      chest radiographs in a population of patients over 50 years of age seen at two
      large but differing metropolitan hospitals in a major American Mid-west city.
      DESIGN AND PATIENTS: The posterior-anterior and lateral chest radiographs of 1363
      patients were reviewed for evidence of DISH at the University of Minnesota
      Hospital and Clinic. There were 500 consecutive inpatient admissions, 540
      consecutive patients who attended the outpatient clinics and 326 patients
      collected from our film archive. A population of 1001 patients seen at Hennepin
      County Medical Center was also studied. It was possible to subclassify this
      latter group with respect to race. RESULTS AND CONCLUSION: Using strict criteria,
      i.e., four or more levels involved, the overall prevalence of DISH in the male
      population over age 50 years was 25% and in the female population over age 50
      years was 15%. This prevalence climbed to 28% in males over 80 years and to over
      35% in males over age 70 years. In females over 80 years, the prevalence was
      found to be 26%. Although our population base was small, DISH was found to be
      less common in the black, Native-American and Asian populations. The prevalence
      of DISH was also found to be far lower in a similar white population with
      osteoporosis. The overall prevalence of DISH was higher than expected in a
      predominantly white population over age 50 years with a lesser incidence in the
      black, Native-American and Asian populations, suggesting a genetic origin of the
      condition.

PMID- 9151371
TI  - MRI appearances of dysplasia epiphysealis hemimelica of the knee.
AB  - OBJECTIVE: The study was undertaken to describe the magnetic resonance imaging
      (MRI) appearances of dysplasia epiphysealis hemimelica (DEH) of the knee and to
      determine whether MRI provides additional information concerning the anomaly
      compared with more traditional methods of diagnosis. DESIGN AND PATIENTS: The
      subjects of the study were three children (one girl and two boys, aged 13 months,
      3 years and 11 years) with DEH of the knee. All the patients had plain films of
      the knee and MRI scans. RESULTS AND CONCLUSION: Plain radiographs showed bone
      overgrowth and asymmetrical ossification centres with adjacent scattered
      calcifications which coalesced to form a lobulated irregular mass. MRI showed a
      definite cartilaginous or osteocartilaginous lesion. Its origin from the
      epiphysis was much more clearly defined. MRI showed the extent of the lesion non
      invasively, as well as any potential cleavage plane between the epiphysis and the
      mass lesion. Abnormal surface nodularity and joint involvement could be
      determined. It is concluded that plain films supplemented with MRI provide the
      greatest amount of diagnostic information in cases of DEH. MRI is useful to show
      the exact location and extent of the lesion, any joint involvement and any
      potential cleavage between the epiphysis and the mass lesion.

PMID- 9151372
TI  - MRI in chronic recurrent multifocal osteomyelitis.
AB  - OBJECTIVE: To review our experience of chronic recurrent multifocal osteomyelitis
      (CRMO) and to assess the value of MRI in this rare disease, which mainly affects
      children and adolescents. DESIGN AND PATIENTS: Seventeen patients from our
      departments were reviewed. All underwent conventional radiography and MRI, and
      most had bone scintigraphy. All had undergone bone biopsy, with microbiological
      and histopathological examinations, to exclude infectious disease, tumours and
      tumour-like lesions. RESULTS AND CONCLUSION: CRMO affects predominantly the
      tubular bones of the limbs, followed by the clavicle and the spine. Other
      locations are rare. Diagnosis is important in avoiding unnecessary diagnostic
      procedures and to initiate appropriate therapy, and is usually based on a
      characteristic course and the appearances on radiography. However, CRMO lesions
      of tubular bones and the spine exhibit quite characteristic MRI features which
      support the diagnosis, while the appearance of the early clavicular lesion is non
      specific. At all sites of CRMO in the skeleton, MRI is valuable in assessing the
      extent and activity of the lesion. It may exclude pyogenic involvement of the
      bone and soft tissues and guide effective biopsy.

PMID- 9151373
TI  - Morel-Lavallee effusions in the thigh.
AB  - OBJECTIVE: To assess the radiological features of Morel-Lavallee effusion in the
      thigh. DESIGN AND PATIENTS: A retrospective study of clinical records and
      radiological studies was carried out on three patients with Morel-Lavallee
      effusion. RESULTS AND CONCLUSIONS: Ultrasound and computed tomography (CT) were
      able to locate the effusion in the three patients. CT demonstrated a capsule
      around the lesion. A fluid-fluid level was visible with both techniques.
      Ultrasound and CT are good methods for assessing patients with Morel-Lavallee
      effusion of the thigh. CT can be used to distinguish patients requiring surgical
      treatment from those who could be treated by conservative measures.

PMID- 9151374
TI  - Dedifferentiated parosteal osteosarcoma of the radius.
AB  - A 35-year-old woman presented with a painful swelling in the left distal radius
      that had been present for 1 year. Radiography and computerized tomography
      revealed a sclerotic surface lesion that had grown over the year and eroded the
      cortex. Histological examination demonstrated two distinct components: a
      cartilaginous low- to moderate-grade osteosarcoma on the surface and a high-grade
      osteosarcoma in the intramedullary component. This case is uncommon in two
      aspects: the radius is a rare site for such a tumor and the dedifferentiation was
      revealed at the time of the first surgery and was not secondary to recurrence.

PMID- 9151375
TI  - Benign giant cell tumor of bone with osteosarcomatous transformation
      ("dedifferentiated" primary malignant GCT): report of two cases.
AB  - It is not uncommon for sarcomatous transformation of giant cell tumor (GCT) of
      bone to occur after radiation, but rarely does malignant transformation occur
      spontaneously, with less than 15 cases reported up to 1995. Only four of these
      cases have been documented in detail. We report two additional cases of GCT of
      bone spontaneously transforming or "dedifferentiating" into osteosarcoma without
      radiation therapy. The first case is absolutely unique and most interesting in
      that the dedifferentiation process occurred in one of multiple GCT lung
      metastases 6 years after successful eradication of a primary tibial tumor. The
      right lung was resected due to development of a large tumor, and at pathologic
      examination, demonstrated several small nodules of conventional GCT and a much
      larger, 14-cm mass composed of a mixture of GCT and high-grade osteosarcoma. The
      second case involved a physician, who had a large tumor in the sacrum with vague
      symptoms for 8 years. Open biopsy revealed conventional, benign GCT of bone with
      a secondary aneurysmal bone cyst. Complete curettage 2 weeks later revealed, in
      addition to areas of conventional, benign GCT a second component of very high
      grade osteosarcoma. Both patients died less than 1.5 years from diagnosis. This
      report of osteosarcomatous transformation of a conventional GCT of bone
      strengthens the theory that there is a mesenchymal cell line in GCT that may
      spontaneously transform to sarcoma.

PMID- 9151376
TI  - Xanthomatous infiltration of ankle tendons.
AB  - We present a case of type II hyperbetalipoproteinemia in a patient whose
      diagnosis had been previously unrecognized, and who had previously been
      misdiagnosed with rheumatoid arthritis and later gout. Radiographic and MR
      imaging features of the patient's ankles were pronounced but otherwise typical of
      xanthomatous infiltration. Radiologic assessment can be useful in permitting a
      specific diagnosis to be made in patients with periarticular and tendinous
      swelling.

PMID- 9151377
TI  - Periosteal gouty tophi of the anterior mid tibia.

PMID- 9151379
TI  - The expression of CD4 and CD8 molecules conditions the behavior of V beta +
      murine thymocytes upon superantigenic challenge.
AB  - We investigated the capacity of the Staphylococcal enterotoxin (SE) B, a
      superantigen (SAg) specific for TCR V beta domain, to modulate V beta 8+
      thymocytes selection in adult mice. Thymocytes were collected at various time
      intervals after SEB injection (10 and 100 micrograms) and V beta 8+ modulation
      was analysed by three color flow cytometry. SEB failed to affect V beta 8+
      thymocytes comprised in the less mature compartments, namely, CD4+8+ and CD4-CD8
      , whereas it selectively affected V beta 8+CD4+8+ (downward modulation) and V
      beta 8+CD4-8+ thymocytes (upward modulation). The different response to SEB
      challenge between CD4+8- and CD4-8+ thymocytes appeared dependent on the CD4/MHC
      class II interaction, as V beta 8+CD4-8+ thymocytes carrying a transgenic CD4
      molecule capable of interacting with MHC class II showed the same response of V
      beta 8+CD4+8- thymocytes. At variance with thymocytes, however, V beta 8+CD4+8-
      and V beta 8+CD4-8+ splenic T lymphocytes responded to SAg challenge in identical
      manner (upward modulation) highlighting the importance of maturation status
      and/or microenvironment in SAg response. V beta 8+ thymocytes remaining in the
      thymus were assessed for their capacity to respond to a SAg challenge. Thus,
      thymocytes were obtained at various time intervals after SEB injection and
      cultured in the presence of SEB or SEA, a Sag specific for V beta 10 as control.
      A reduced mitotic response to SEB but not to SEA was noticed irrespective of the
      number of V beta 8+ responding cells present in culture. It is concluded that
      SAgs affect TCR specific thymocytes by conditioning their redistribution and
      inducing an anergic status.

PMID- 9151380
TI  - Interleukin (IL)-2 deficiency aggravates the defect of natural killer cell
      activity in AIDS patients.
AB  - A decrease in natural killer (NK) cell activity is a common feature of the immune
      dysfunction found in patients with human immunodeficiency virus (HIV)-induced
      acquired immune deficiency syndrome (AIDS). The present study was aimed at
      exploring the NK and the lymphokine-activated killer (LAK) cell activities of
      lymphocytes from HIV-seropositive subjects. The in vitro production of
      interleukins (IL-2 and IL-10) in response to mitogens was also studied. Two
      groups of HIV-seropositive subjects were studied: asymptomatic and AIDS patients.
      Controls were normal blood donors. The NK cell activity in peripheral blood
      mononuclear cells (PBMC) from AIDS patients was significantly lower than that in
      PBMC from both HIV-seronegative subjects and asymptomatic patients. There was no
      significant difference between asymptomatic patients and controls. Exposure of
      PBMC from all three groups of individuals to an optimal dose of IL-2 in vitro
      enhanced LAK cell activity. At all three effector: target cell ratios, the LAK
      activity in AIDS patients remained below that in normal subjects. However, the
      proportional increase of lytic activity with IL-2 was slightly higher in AIDS
      patients than in HIV-seronegative subjects. The mitogen-induced production of IL
      2 was especially reduced in AIDS patients. In contrast, very high levels of
      mitogen-induced production of IL-10 were found in the AIDS group, as compared to
      asymptomatic subjects or to controls. We therefore conclude that the alteration
      of NK cell activity occurs at an advanced stage of HIV infection, that the
      reduction of cytotoxic activity is partially restored by exogenous IL-2, and that
      decreased production of IL-2 and increased production of IL-10 may account for
      part of this reduction in cytotoxicity.

PMID- 9151378
TI  - SAPALDIA: methods and participation in the cross-sectional part of the Swiss
      Study on Air Pollution and Lung Diseases in Adults.
AB  - SAPALDIA--the Swiss Study on Air Pollution and Lung Diseases in Adults--focuses
      on the long term health effects of low to moderate levels of air pollutants as
      typically seen in different parts of Switzerland. The aim of the SAPALDIA cross
      sectional study carried out in 1991 was to determine the prevalence of bronchial
      asthma, chronic bronchitis and allergic conditions in the adult population of
      Switzerland and to identify and to determine the respective importance of
      potentially influencing factors. These could be both personal (smoking habits,
      allergy status, family history, occupation) and environmental (outdoor and indoor
      pollution, aeroallergens, climate). A further aim of the cross-sectional study
      consisted in the identification of individuals susceptible to present symptoms
      during a two year observation period and to be included in the SAPALDIA follow-up
      study. This technical report represents the methodological documentation for the
      cross-sectional study of SAPALDIA. The instruments and the methods of
      standardisation are presented and discussed. The medical examination consisted of
      a computerised interview using a standardised questionnaire, the taking of a
      blood sample for serological tests, allergy skin testing, the measurement of end
      expiratory CO and body height, and pulmonary function testing followed by
      methacholine challenge testing or bronchodilatation testing. The pattern of
      participation and the 9651 participants of the study, representing 59.3% of the
      sample, are described. Based on information on non-participants gained by
      telephone interviews and mailed short questionnaires, possible selection biases
      are quantified and discussed.

PMID- 9151381
TI  - Thymic interdigitating cells express thioredoxin (TRX/ADF): an
      immunohistochemical study of 82 thymus and thymoma samples.
AB  - Thymic ID cells are involved in the differentiation of mature T cells which are
      resistant against apoptosis. TRX/ADF is a potent thiol-related reducing agent,
      acts as a redox regulator, and it can attenuate the induction of apoptosis of T
      lineage lymphocytes. In the present study, 42 thymoma-free thymus and 40 thymoma
      samples were examined to identify the expression of TRX/ADF in human thymic
      tissue. TRX/ADF high-producer (TRXh) cells with cytoplasmic protrusions were
      found distributed in the thymic medulla. These TRXh cells were negative for CD3,
      a lymphocyte marker, keratin, an epithelial cell marker, and CD68 or lysozyme,
      macrophage/monocyte markers, but were positive for S100 protein and HLA-DR
      complex. Our results revealed that the TRXh cells in the thymic medulla were ID
      cells. As TRX/ADF has an important and fundamental role in cellular responses
      acting against oxidative stress, TRX/ADF may provide an explanation of cellular
      interaction between the medullary ID cells and the mature T cells.

PMID- 9151382
TI  - Post-thymic T-cell development in the rat.
AB  - The presence or absence of CD4, CD8, Thy-1, RT6 and CD45RC revealed a number of T
      cell subpopulations in the rat. Vascular thymus transplantation was used in RT7
      congenics to establish the lineage relationship between these subpopulations by
      following phenotypic changes after thymus emigration. We found that recent thymic
      emigrants exhibit the Thy-1+/RT6-/CD45RC- phenotype and express either CD4 or
      CD8. Within 11 days after emigration, these cells differentiated into Thy-1
      /RT6+/CD45RC+ cells. From 33 to 76 days following transplantation, a proportion
      of the latter lost RT6 and/or CD45RC expression, suggesting further
      differentiation. The pathway of 'mature' T-cell differentiation could be
      reconstructed from these data and analysis of the differences between T-cell
      subsets in thymectomized and normal control rats. End-stages of post-thymic T
      cell differentiation in the rat were most likely to be Thy-1-/RT6+/CD45RC- and
      Thy-1-/RT6-/CD45RC+ T cells.

PMID- 9151383
TI  - Antibodies' problem in invertebrate immunology.

PMID- 9151384
TI  - Acquisition and use of DNA-based HLA typing data in bone marrow registries.
AB  - The increased use of DNA-based typing techniques has improved the accuracy and
      reliability of HLA types assigned to patients requiring an allogeneic bone marrow
      transplant and their potential donors, facilitating better donor selection. The
      benefits of this technology, which will completely replace serologic typing
      within the next few years, have not yet been fully exploited since the typing
      information obtained in the form of DNA sequence polymorphisms is presently
      converted to an HLA allelic type for submission to a registry. Furthermore,
      within the registry, the allelic type may be further converted to a serologic
      antigen for use in the search and match process. Because the current nomenclature
      system makes selection of donors who are likely to provide optimal matches
      difficult, it is critical that DNA-based HLA typing data be recorded by
      registries as sequence polymorphisms tested as positive or negative rather than
      interpreted HLA types and that searching and matching utilize these
      polymorphisms. Until this transition is complete, we will not fully utilize this
      powerful HLA typing technology to best serve those patients seeking unrelated
      donors.

PMID- 9151385
TI  - Extensive HLA class II studies in 58 non-DRB1*15 (DR2) narcoleptic patients with
      cataplexy.
AB  - Narcolepsy is a sleep disorder that has been shown to be tightly associated with
      HLA DR15 (DR2). In this study, 58 non-DR15 patients with narcolepsy-cataplexy
      were typed at the HLA DRB1, DQA1 and DQB1 loci. Subjects included both sporadic
      cases and narcoleptic probands from multiplex families. Additional markers
      studied in the class II region were the promoters of the DQA1 and DQB1 genes, two
      CA repeat polymorphisms (DQCAR and DQCARII) located between the DQA1 and DQB1
      genes, three CA repeat markers (G51152, T16CAR and G411624R) located between DQB1
      and DQB3 and polymorphisms at the DQB2 locus. Twenty-one (36%) of these 58 non
      DR15 narcoleptic patients were DQA1*0102 and DQB1*0602, a DQ1 subtype normally
      associated with DRB1*15 in DR2-positive narcoleptic subjects. Additional
      microsatellite and DQA1 promoter diversity was found in some of these non-DR15
      but DQB1*0602-positive haplotypes but the known allele specific codons of
      DQA1*0102 and DQB1*0602 were maintained in all 21 cases. The 37 non
      DQA1*0102/DQB1*0602 subjects did not share any particular HLA DR or DQ alleles.
      We conclude that HLA DQA1*0102 and DQB1*0602 are the most likely primary
      candidate susceptibility genes for narcolepsy in the HLA class II region.

PMID- 9151386
TI  - MHC-DRB allelic sequences incorporate distinct intragenic trans-specific
      segments.
AB  - The second exon of primate MHC-DRB genes encodes discrete areas of allelic
      hypervariability (HVR), which are used as the basis for lineage assignments to
      determine genetic and evolutionary relationships. Comparisons of these regions
      have led to the "trans-species hypothesis", which proposes that certain MHC
      alleles from one species are more closely related to those from other species
      than they are to each other; i.e., that allelic lineages are ancestral in origin.
      We evaluated this paradigm in an analysis of macaque and baboon MHC-DRB genes
      using oligotyping and sequencing of 87 new nonhuman primate DRB alleles. A
      remarkable conservation of sequence motifs in the HVRIII region (codon 60-79) was
      observed, detected both by hybridization and by sequencing; some of these motifs
      were found in species such as prosimians that have diverged from the human
      lineage 50 MYA. However, these fixed HVRIII motif sequences nevertheless occur on
      a background of diverse lineages suggesting that it is the segmental motif,
      rather than the allele per se which is trans-specific in origin. Sequences within
      the first hypervariable region (codons 7-14) identified lineage assignments to
      several DRB loci (DRB1, DRB3, DRB4, DRB5, DRB6 and DRB7), although a large number
      of DRB nucleotide sequences did not correspond to a defined allelic motif,
      suggesting that many of the nonhuman sequences lack human HVRI homologs and have
      accumulated additional intraspecies variation subsequent to speciation. While
      there are certain allelic lineages in HVRI that show trans-species conservation,
      other sequence motifs seem purely species-specific. These differences suggest
      that HVRI and HVRIII regions have distinct mechanisms for maintenance of trans
      specific sequence elements, with different evolutionary histories for segmental
      nucleotide conservation.

PMID- 9151387
TI  - CpG methylation patterns in the 5' part of the nonclassical HLA-G gene in
      peripheral blood CD34+ cells and CD2+ lymphocytes.
AB  - A dominant goal of research focused on the nonclassical human leukocyte antigen G
      (HLA-G) gene is to understand the molecular mechanism involved in its limited
      expression. In the present report, we examined DNA methylation as a potential
      regulatory mechanism of HLA-G transcription in two cell types of the adult
      lymphomyeloid lineage: CD2+ lymphocytes express several mRNA isoforms while
      transcripts are undetectable in CD34+ hematopoietic cells. The methylation status
      of 63 CpG sites in the promoter and in the 5' CpG island was established using
      bisulfite-treated genomic DNA sequencing. Methylation was first analyzed by the
      direct sequencing of bisulfite-treated and amplified products. The general
      patterns of CpG methylation in the 5' part of the gene were found to be similar
      for CD34+ cells and CD2+ lymphocytes: the distribution of methylation was not
      uniform across the 63 CpG sites. In the promoter region, both CpG dinucleotides
      were partially or fully methylated whereas in the CpG island, several CpG sites
      were totally demethylated. Unexpectedly, in HLA-G positive CD2+ lymphocytes, a
      great number of CpG dinucleotides displayed a higher frequency of methylation
      relative to that found in CD34+ cells. However, the sequence analysis of cloned
      products revealed that the molecules have different methylation patterns which
      suggests that the HLA-G gene is differentially expressed in CD2+ cells. Our
      results suggest that methylation is not the sole mechanism that achieves the
      repression of HLA-G transcription in immature CD34+ cells.

PMID- 9151388
TI  - HLA-B typing by allele separation followed by direct sequencing.
AB  - Due to the enormous allelic diversity of the HLA-B locus, it has been difficult
      to design an unambiguous molecular typing method for the alleles at this locus.
      Here we describe a technique for the direct sequencing of HLA-B alleles.
      Initially, HLA-B alleles were PCR-amplified after locus-specific reverse
      transcription of RNA. Alleles were then separated using denaturing gradient gel
      electrophoresis (DGGE), which separates DNA fragments based on their sequence
      composition. Amplification products were excised from the gel and eluted DNA was
      reamplified and directly sequenced. The derived sequences were aligned to a
      database of published HLA-B sequences, and an initial allele assignment was made.
      This approach was theoretically sufficient to type 92 of the 118 known HLA-B
      alleles. The majority of the remaining 26 alleles contain differences at the
      beginning of exon 2, a region outside the DGGE-separated PCR products. Therefore,
      we used heterozygous sequencing of this region to identify 19 of these 26
      alleles, raising the resolution power to 111 alleles. Using this technique, we
      analyzed immortalized cell lines and blood samples from several different
      sources. Nine immortalized cell lines were obtained from the 10th International
      Histocompatibility Workshop (IHWS) and nine were derived from aboriginal peoples.
      Additionally, 25 blood samples were acquired from a panel of donors previously
      shown to be difficult to type using serological techniques. Altogether, using
      this new method of allele separation by DGGE followed by direct sequencing, we
      typed 52 different alleles from 57 individuals, covering 40 serological
      specificities.

PMID- 9151389
TI  - Five HLA-B22 group alleles in Japanese.
AB  - HLA-B22-group alleles in Japanese were identified using PCR-single-strand
      conformation polymorphism (SSCP) and sequence analyses. We analyzed genomic DNAs
      obtained from Japanese individuals positive for HLA-B22 group antigens (HLA-B54,
      B55, B56) including two locally proposed splits (B55.2, and B22N). In the SSCP
      analysis of both exons 2 and 3, we discriminated five different B22-group
      alleles. Each allelic pattern corresponded to each serological split antigen.
      Direct sequencing analysis of exon 2 and exon 3 showed that alleles encoding B54,
      B55.1 and B56 antigens in Japanese are encoded by B*5401, B*5502 and B*5601,
      respectively, and those encoding B55.2 and B22N antigens are previously
      unidentified alleles, B*5504 and B*5603, respectively. Full-length cDNA
      sequencing showed that the B*5603 sequence is identical to those of B*5501,
      B*5502, B*5601, and B*5602 in exons 1 to 2 except for a synonymous substitution
      at nucleotide position 165 in exon 2. On the other hand, the sequence of exons 3
      to 7 was identical to those of some B15 and B46 alleles, suggesting that B*5603
      was generated by a recombination event between one of the B55 and B56 alleles and
      one of the B15 and B46 alleles in intron 2. As for B*5504, the entire exon 1 to 7
      sequence is identical to that of B*5502 except that the 5'-half of the exon 3
      sequence is identical to those of some B7, B27, B40 and B48 alleles, suggesting
      that an event such as gene conversion, segmental exchange, or double
      recombination occurred in this region.

PMID- 9151390
TI  - Serologic ambiguity and allelic frequency of the HLA-B40 family in the Korean
      population.
AB  - The most frequently identified HLA-B type in Koreans is HLA-B40 (13.4%). Due to
      the lack of mono-specific alloantisera and cross reactivity of sera used as
      typing reagents, discrimination between the serologic splits of B40, B60 and B61,
      has been a problem in tissue typing laboratories. In this study, an efficient PCR
      SSP typing system was established to distinguish B60 and B61 and to assess the
      difficulty in serologic assignment for these types. The SSP system was also used
      to elucidate the frequency of B40 alleles (B*4001-B*4008) encoding B40 molecules
      in the Korean population. Eighty eight unrelated individuals identified
      serologically as B40 positive were selected from 358 consecutive volunteers from
      the unrelated bone marrow registry. Seven sets of PCR that amplify exons 2 and 3
      of the HLA-B gene using 10 sequence specific primers (SSP) were used for
      discrimination between B60 and B61, and for B40 allelic typing. A clear
      discrimination of B60 and B61 was possible in all samples including 48
      serologically ambiguous samples (B60-14/48; B61-34/48) and 5 potentially B40
      homozygous samples (B60/ B61 heterozygotes-4/5; B60 homozygote-1/5). Therefore,
      the use of a focused SSP approach enhances serologic definition of HLA types in
      routine clinical testing. In allelic typing, all B60 samples (26) appeared to be
      B*4001, but B61 samples revealed more heterogeneity (B*4002-36/58, B*4003-4/ 58,
      B*4006-18/58). In addition, B*4003 seemed to be closely associated with the A24
      Cw3-DRB1*02 haplotype (3/4). The characterization of allele frequency as well as
      haplotypic association will be helpful in determination of the optimal size of
      the volunteer marrow donor pool in the Korean population.

PMID- 9151391
TI  - Molecular analysis of HLA-B35 alleles and their relationship to HLA-B15 alleles.
AB  - The HLA-B35 serotype is one of the largest allelic groups of HLA class I
      molecules and includes four isotypes. Of the four, the B35 variant isoform is
      relatively rare and is the most acidic form. DNA sequencing of the rare isoforms
      revealed three alleles, B*1522, B*3511, and B*3517. A phylogenetic tree of HLA
      B15- and HLA-B35-related alleles for the exon 2 and 3 nucleotide sequences showed
      that exon 2 of B*1522 clusters with B35 alleles whereas exon 3 clusters with B15
      alleles. Branches of the tree suggest that the serodeterminants of B35, B62, B63,
      and B70 may reside in the alpha 1 domain, encoded by exon 2. The B*1520 and
      B*1522 genes, which type as B62 and B35, respectively, are hybrid molecules
      alternatively using exon 2 and exon 3 sequences of B*3501 and B*1501. A
      comparison of intron 2 sequences for B*3501, B*1501 and B*1522 suggests that the
      recombination site may have been in the region at the 3' end of intron 2. Despite
      being flanked by two highly polymorphic exons (exons 2 and 3), intron 2 is
      relatively well conserved in the B-locus, and it is characterized by seven to
      eight tandem repeats of the CGGGG pentanucleotide. A high degree of sequence
      homology and repetitive sequences are essential for a significant frequency of
      recombination. In this report, we reveal more about the complex evolutionary
      history of the HLA-B alleles.

PMID- 9151392
TI  - HLA-DR 52- and 51-associated DRB1 alleles in Kenya, east Africa.
AB  - The genes of the major histocompatibility complex (MHC) are amongst the most
      polymorphic loci known in the human population. The population genetics of the
      MHC encoded HLA loci of sub-Saharan Africa are of major interest because of their
      particular genetic diversity. Here we report on the HLA-DR 52- and 51-associated
      determinants of the DRB1 loci observed in 165 East African individuals studied in
      Nairobi, Kenya. The HLA-DR typing was done by serologic and by molecular DNA
      techniques (PCR-SSOP). The most frequent allele identified was DRB1*1101,
      followed by DRB1*1503 and DRB1*1302. Some unexpected alleles were repeatedly
      identified: DRB1*1108, DRB1*1316 and DRB1*1421. Most of the DR 52- and 51
      associated DRB1 alleles were correctly identified by serology as part of the DR3,
      DR5, DR6 and DR2 groups respectively. The HLA-DRB1 profile reported here
      corroborates previous genetic and linguistic data supporting the concept that the
      Eastern African Black population is genetically distinct from other African Black
      populations. This has important implications in public health issues related to
      the genetic profile of a population (transplantation, vaccine design for
      example).

PMID- 9151393
TI  - Monoclonal antibodies specific for porcine monocytes/macrophages: macrophage
      heterogeneity in the pig evidenced by the expression of surface antigens.
AB  - Macrophages are widely distributed in most tissues of the body, where they play
      important roles in host defense and repair of tissue damage. In this report we
      describe the production and characterization of a panel of six monoclonal
      antibodies (mAb) against porcine macrophages and their use for phenotyping tissue
      macrophages. All mAbs were produced by immunizing mice with porcine alveolar
      macrophages. Three of them (2A10/11, 3B11/11 and 3F7/11) react mainly with
      macrophages and, at a lower extent, blood monocytes, whereas the others (1E12/11,
      2C12/10 and 4E9/11) also recognize granulocytes. Antigens recognized by these
      antibodies could be characterized by Western blot and/or immunoprecipitation,
      with the exception of that one recognized by 2C12/10. By their behavior in SDS
      PAGE under reducing and nonreducing conditions, all seem to be single
      polypeptides, whose apparent molecular weight under reducing conditions are:
      1E12/11 and 3B11/11 larger than 204 kDa; 2A10/11, 150 kDa; 4E9/11, 125-170 kDa;
      and 3F7/11, 135 kDa. Immunohistochemical analyses of both lymphoid and non
      lymphoid organs using these mAbs reveal important antigenic heterogeneity among
      tissue macrophages. These mAbs are, therefore, useful tools for the study of
      porcine macrophage maturation and differentiation and for determining their
      heterogeneity both in normal and pathological conditions.

PMID- 9151394
TI  - A novel HLA-DRB1*11 allele (DRB1*1127).

PMID- 9151395
TI  - HLA-DQA1 genotyping by bi-directional sequencing of PCR-amplified DNA spanning
      exon 2.
AB  - We describe a simple, reliable technique for HLA-DQA1 genotyping based on direct
      DNA sequencing of PCR amplified fragments from genomic DNA. The alleles of DQA1
      can be divided into two subsets, with one subset demonstrating a 3 base deletion
      in exon 2 relative to the other. Typing heterozygous individuals who possess one
      allele from each sub-group can be difficult using a direct sequencing approach,
      since the two overlapping DNA sequences move out of phase by 3 nucleotides once
      the point of deletion is reached. The complete sequence is obtained by performing
      two separate sequencing reactions with fluorescent dye primers, coming from
      either end of the template. This allows all heterozygous positions in exon 2 to
      be unambiguously assigned.

PMID- 9151396
TI  - Human TAP1 polymorphisms detected by denaturing gradient gel electrophoresis.
AB  - Presentation of endogenous peptides by major histocompatibility complex class I
      (MHC) molecules is controlled, in part, by the Tap1 and Tap2 genes in the MHC
      class II region that encode a heterodimeric peptide transporter. Polymorphisms of
      human Tap1 in normal individuals have now been investigated systematically by
      denaturing gradient gel electrophoresis (DGGE) analysis of fragments of genomic
      DNA generated by the polymerase chain reaction. Polymorphisms identified by
      distinctive DGGE band patterns were confirmed by DNA sequencing. In addition to
      four previously described polymorphisms in the open reading frame, DGGE detected
      three new polymorphisms: a G-->T substitution in the promoter region, a 10-bp
      insert in intron 9, and a G-->T substitution 80-bp downstream of the translation
      termination codon.

PMID- 9151397
TI  - The novel HLA-DRB1*0807 allele is present in a Carib Amerindian population: the
      Yucpa.
AB  - Nucleotide sequences of five novel HLA-DRB1*08 alleles have been recently
      reported but their frequency in different populations is still unknown. The
      presence of DRB1*08 variants among Carib-speaking Yucpa Amerindians of the Perija
      Range in the border between Colombia and Venezuela was tested by PCR-DNA typing.
      DRB1*0807 was the only DRB1*08 variant found in this population with a frequency
      of 0.1250. Until very recently, DRB1*0802 was the predominant DRB1*08 allele
      present among full-blooded Amerindians, but in the last 3 years DRB1*0804 has
      been found in 2 South American tribes and *0811 in 2 North American tribes. The
      description of a new functional DRB1*08 variant in Amerindians suggests that
      extensive gene polymorphism among Amerindians might not be limited to the HLA-B
      Class I locus.

PMID- 9151398
TI  - FIV induced encephalopathy: early brain lesions in the absence of viral
      replication in monocyte/macrophages. A pathogenetic model.
AB  - FIV induced encephalopathy represents a model for the study of the
      neuropathogenesis of AIDS. It has yet to be determined whether massive viral
      replication is a prerequisite for the development of early brain lesions. Using a
      drug delivery system developed by us, we have shown that early encephalic lesions
      appear in FIV infected subjects even when viral transport within the brain has
      been markedly reduced or blocked.

PMID- 9151399
TI  - Relationship between radical production and natural killer cytotoxic factor
      (NKCF) in canine natural killer (NK) cell-mediated cytotoxicity.
AB  - The relationship between radical production and natural killer cytotoxic factor
      (NKCF) release via canine natural killer (NK)-mediated cytotoxic mechanism was
      examined. Radical production and NKCF release was induced in NK cells stimulated
      with either dead target cells, or their cytoplasmic membranes, as well as live
      target cells. Canine NKCF evoked target cell lysis but did not induce radical
      production. Radical production was inhibited by the addition of Tiron or n-propyl
      gallate, whereas NK-mediated cytotoxicity and NKCF release were only inhibited by
      the addition of n-propyl gallate. These results suggested that radical production
      and NKCF release may be induced by the contact and binding of NK cells to the
      target cell cytoplasmic membrane. Therefore, the release of NKCF from NK cells
      attached to the target cell cytoplasmic membrane may be associated with the
      production of radicals, especially hydroxyl radicals.

PMID- 9151400
TI  - Further analysis of the phenotype and distribution of tumor cells in sporadic B
      cell and T-cell lymphomas in the lymph node and spleen of cattle.
AB  - Immunohistologic studies were performed to identify the phenotype and
      distribution of neoplastic lymphocytes in the spleens of BLV-negative animals
      examined by PCR and diagnosed as having sporadic bovine leukosis. Tumor cells
      from three cases of sporadic bovine leukosis were identified as of B-cell
      lineage. Tumor cells from three additional cattle were identified as CD3+ CD4-
      CD8+, CD3+ CD4- CD8-, and CD3+ CD4- WC1+, respectively. The last case was
      diagnosed as a gamma/delta T-cell lymphoma. Differences in morphology
      proliferative characteristics were recognized between B- and T-cell type
      lymphomas. The tumor cells in B-cell type lymphoma were characterized as follows:
      medium or large in size, round or polymorphic nucleus with rough chromatin with
      some tumor cells containing a convoluted nucleus. These tumor cells of B-cell
      type lymphoma were present in the red pulp and periarteriolar lymphoid sheath.
      Tumor cells of the T-cell type lymphoma were uniformly smaller than B-cell type
      and present around arteries or replaced red pulp of the spleen.

PMID- 9151402
TI  - Postnatal development of lymphocyte subpopulations in the intestinal mucosa in
      goat.
AB  - The incidence and location of CD2+, CD4+, CD8+ and gamma/delta T-lymphocytes and
      B-lymphocytes were studied in the intestinal mucosa in goats of one week, one
      month, three months and seven months old, using monoclonal antibodies and
      immunohistochemical methods. At all ages CD2+ lymphocytes were the major
      subpopulation in the intestinal mucosa, more numerous in the small than in the
      large intestine and in the villi than in the crypt region. In one week-old
      animals most of CD2+ lymphocytes were scattered in the lamina propria and the
      number of lymphocytes that expressed CD4 was less than those that expressed CD8,
      resulting in a CD4/CD8 ratio less than 1. CD2+ lymphocytes increased markedly
      until one month old, with a higher increase of CD4+ subpopulation than CD8+ with
      an inversion of the CD4/CD8 ratio. CD4+ lymphocytes were localised in the lamina
      propria forming clusters, whereas CD8+ lymphocytes were scattered peripherally
      under the epithelium and in older animals from three month old, CD8+ lymphocytes
      were also abundant between epithelial cells. The gamma/delta T-lymphocytes
      recognised with the mAb CACTB6A represented a minor subpopulation located between
      epithelial cells or in the lamina propria, no evident changes were observed with
      age. IgM+ cells were a minor subpopulation in all animals (never higher than 1
      cell per 1500 microns-2) located in the crypt region of the lamina propria.

PMID- 9151401
TI  - Factors controlling haemopoiesis in ovine long-term bone marrow cultures.
AB  - We describe an adaptation of the Dexter technique for obtaining ovine long-term
      bone marrow cultures able to sustain haemopoiesis in vitro for long periods. Two
      inocula of bone marrow cells collected at three-five weeks interval, in IMDM
      supplemented with fetal calf serum (10%), horse serum (10%) and hydrocortisone (5
      x 10(-7) M), gave rise to the growth of an adherent cell layer which supported,
      in most cases, active haemopoiesis for up to 15 weeks. The cell layer was
      composed of macrophages, fibroblasts and adipocytes. Haemopoietic cells formed
      large foci of "cobblestone" areas. Haemopoietic progenitors were also released
      into the supernatant medium and were detectable by clonogenic assay. Granulocytes
      and monocyte-macrophages differentiated in the cultures in constant proportion
      until week five, when the monocytic lineage superseded the myelocytic one. These
      cultures, between weeks five and twelve, produced colony forming cells in a
      constant pattern, indicating the presence and self renewing of early haemopoietic
      progenitor cells.

PMID- 9151403
TI  - Trk-like proteins during the post-hatching growth of the avian bursa of
      Fabricius.
AB  - Neurotrophins are growth factors acting on responsive cells through membrane
      receptors identified as Trk tyrosine kinase proteins (A, B and C). Trks are
      present in the mammalian lymphoid organs, and indirect evidence suggests that
      they are also present in the avian bursa of Fabricius. This study was designed to
      analyze (a) the occurrence and localization of Trk proteins in the bursa of
      Fabricius; and (b) whether the post-hatching growth of the organ (from hatching
      to 75 days) involves cells expressing Trk proteins. We used pigeon bursae of
      Fabricius, and rabbit polyclonal antibodies against specific epitopes of TrkA,
      TrkB and TrkC. Cytokeratins and vimentin were studied in parallel with label non
      lymphoid cells of the bursal follicles. Immunoreactivity (IR) for all assessed
      antigens was found in specific non-lymphoid cells. From hatching to 15 days, TrkB
      like IR was found outside the follicles in cells localized beneath the follicle
      associated (FAE) and interfollicular (IFE) epithelium. Between 30-75 days TrkB
      like IR labelled the medullary secretory dendritic cells (SDC). The density of
      SDC displaying IR increased up to 60 days. TrkA-like and TrkC-like IR was
      primarily observed in FAE and IFE, but also in the medullary reticular epithelial
      cells (REC) up to 15 days. The present results provide evidence of the
      occurrence, localization and post-hatching changes in Trk proteins in avian bursa
      of Fabricius. Trks were localized on non-lymphoid cells which participate in
      providing the adequate microenvironment for B lymphocyte maturation. Furthermore,
      the cell segregation in the expression of Trks suggests specific roles for their
      ligands in controlling the function of medullary SDC and REC, hence bursal
      lymphoid follicle physiology.

PMID- 9151404
TI  - Transforming growth factor-beta isoforms in the developing chicken intestine and
      spleen: increase in transforming growth factor-beta 4 with coccidia infection.
AB  - Expression of transforming growth factor-betas 2, 3 and 4 (TGF-beta) in the
      developing chicken intestine and spleen was investigated using specific cDNA
      probes and antibodies for the different TGF-beta isoforms. Coordinate expression
      of the mRNAs for TGF-beta s 2, 3 and 4 was detected in the embryonic intestine by
      8 days, with maximal expression of the mRNAs for TGF-beta s 2 and 4 occurring at
      12 and 19 days, respectively, while expression of TGF-beta 3 mRNA remained
      constant during this time. While specific antibodies for TGF-beta s 2, 3 and 4
      could detect only weak immunohistochemical staining of the intestinal epithelium
      in 4-, 12- and 16-day-old embryos, intense staining for TGF-beta s 2, 3 and 4 was
      detected in the tips of the intestinal villi of 19-day-old embryos. In the
      spleen, expression of the mRNAs for TGF-beta s 2 and 3 increased in the newly
      hatched chick compared with the embryo and then decreased in the adult to levels
      that were lower than in the embryo; expression of TGF-beta 4 mRNA increased
      progressively with developmental age, with expression in the adult spleen being
      significantly higher than in the embryonic and hatchling spleen.
      Immunohistochemical staining of spleens showed a selective increase in the level
      of reactive TGF-beta 4 with increasing developmental age, while staining for TGF
      beta s 2 and 3 was constant during development. After infection of 1-month-old
      chickens with coccidian parasite, expression of TGF-beta 4 mRNAs increased 5-8
      fold in intestinal intra-epithelial lymphocytes and 2.5-fold in spleen cells,
      while expression of the mRNAs for TGF-beta s 2 and 3 remained constant in these
      cells. The results of this study suggest that TGF-beta may play a role in
      development of the intestine and spleen in the chicken and that TGF-beta 4 in
      particular increases after infection of coccidia in the chicken.

PMID- 9151405
TI  - Comparative antibody response in harbour and grey seals naturally infected by a
      morbillivirus.
AB  - The antibody response of free-ranging harbour and grey seals, naturally infected
      by a morbillivirus, was assessed using a virus neutralizing test and a radio
      immunoprecipitation assay. The prevalence of antibody was similar between
      species, however, grey seals had significantly higher virus neutralizing titers.
      Serum from clinically healthy grey seals precipitated the nucleocapsid (N)
      protein along with the hemagglutinin (H) and fusion (F) glycoproteins. By
      contrast, significantly fewer harbour seal sera precipitated the envelope
      glycoproteins and responses were weaker than those of grey seals. One harbour
      seal with acute morbillivirus pneumonia, and two with encephalitis precipitated
      only the N protein. Serum from four harbour seals with encephalitis weakly
      recognized the envelope glycoproteins. Thus, the antibody response of grey seals
      appears more competent than that of harbour seals with respect to morbillivirus
      antigens. We speculate that this difference between the species may be an
      important determinant of morbillivirus susceptibility.

PMID- 9151406
TI  - p53 mutation as a potential cellular factor for tumor development in enzootic
      bovine leukosis.
AB  - Mutations of p53 in the lymphocytes from peripheral blood and from tumoral lymph
      nodes in six naturally occurring bovine leukemia virus (BLV)-infected cows were
      examined. A point mutation of the p53 gene was found in three of six (50%) BLV
      infected cows. These p53 gene mutations resulted in amino acid substitutions of
      codons 144, 167 and 241. The BLV-infected cow in the tumor stage had abnormally
      proliferating monoclonal B-lymphocytes having the p53 mutation. However, the
      mutation was not found in somatic cells, except for tumor cells. These results
      show that p53 mutation plays an important role in the pathogenesis of BLV-induced
      neoplasms, and that the B-lymphocyte bearing p53 mutations may be a target cell
      for tumor formation of enzootic bovine leukosis.

PMID- 9151407
TI  - A sero-epidemiological study of Haemophilus somnus infection in dairy cattle.
AB  - Five repeated cross-sectional serological surveys of 790 dairy cattle in 4 dairy
      herds between December 1985 and February 1987 provided an opportunity to study
      the changes in the seroprevalence of Haemophilus somnus across the 5 surveys and
      with respect to some demographic and disease variables. The demographic variables
      included were age (heifers or cows) and farm, representing two groups of herds
      (two herds in each group, located in the Central and Northern Valleys of
      California). The serological status of cattle as either negative or positive
      against H. somnus, Campylobacter fetus and Leptospira hardjo were determined with
      enzyme linked-immunosorbent assays. Logistic regression analysis was used to
      compute maximum likelihood estimates of adjusted odds ratios and their respective
      95% confidence intervals. The baseline risk of being H. somnus seropositive in
      the cattle observed at first sampling did not vary significantly during the study
      period after adjustment for the effects of covariates. Only at first sampling
      were cows about twice as likely to be H. somnus seropositive than heifers. At
      samplings 1 and 3, but not at 2 and 5, being in the herds of the Central Valley
      appeared protective. In contrast, at sampling 4 the cattle in herds in the
      Central Valley were about 7 times more likely to be H. somnus seropositive. C.
      fetus-positive cattle were about 3 times more likely to be H. somnus seropositive
      at sampling 1 only. The relationship between H. somnus status and L. hardjo was
      not significant during the study period.

PMID- 9151408
TI  - The effect of activation of granulocytes on enzyme release and hydrogen peroxide
      and superoxide production in buffaloes.
AB  - Polymorphonuclear cells kill microorganisms by the stock of antibiotic proteins
      and peptides stored in their lysosomal granules and have the ability to produce
      reactive oxygen intermediates (ROI) such as H2O2, O2-, and HOCl. Since the
      components involved in the microbicidal functions of buffalo (Bos bubalis)
      polymorphonuclear cells (PMN) have not been characterized, an assessment was made
      of the levels of various enzymes, the extent of extracellular release of these
      enzymes, and also their ability to produce H2O2/O2- upon activation with
      opsonized zymosan (OZ) or lipopolysaccharide (LPS). Using GPC-HPLC, OZ was shown
      to be a more potent secretagogue than LPS, causing a significantly greater
      release of low-molecular-weight components. Varying levels of the enzymes
      (myeloperoxidase, lactate dehydrogenase, acid and alkaline phosphatases, beta
      galactosidase, beta-D-glucuronidase, elastase and lysozyme) were recorded in the
      buffalo PMN and both the activators (OZ and LPS) caused significant release of
      all the enzymes except alkaline phosphatase. Both the activators also caused a
      significant increase in H2O2/O2- production by the PMN. However, OZ caused a more
      pronounced activation than LPS. The studies revealed the presence of oxygen
      dependent and oxygen-independent microbicidal systems with buffalo PMN, which
      responded more effectively to zymosan activation.

PMID- 9151410
TI  - A preliminary comparison of plasma fibrinogen concentrations, leukocyte numbers
      and erythrocyte sedimentation rate as non-specific indicators of inflammatory
      conditions in buffalo (Bubalis bubalis).
AB  - The plasma fibrinogen concentration (Fib), total leukocyte count (TLC),
      neutrophil, lymphocyte and monocyte numbers, and the erythrocyte sedimentation
      rate (ESR) were determined in 153 buffaloes suffering from different clinical
      conditions. Fib increased significantly (p < 0.05) in chronic mastitis, pyrexia,
      pyometra, cutaneous abscesses, tail gangrene and acute indigestion, whereas in
      most of the other conditions studied it varied non-significantly. TLC increased
      significantly in chronic mastitis, pyrexia, endometritis, cutaneous abscesses and
      infected skin wounds. An increase in neutrophils was associated with an increased
      TLC. Numbers of lymphocytes varied non-significantly in most of the conditions.
      Monocytes decreased significantly in most of the acute conditions. ESR was
      significantly elevated in all clinical conditions. Significantly increased mean
      Fib values in the different conditions varied from 703 +/- 119 to 725 +/- 140
      mg/dl, while the maximum individual value was 1510 mg/dl in a case of cutaneous
      myiasis. The significantly increased mean TLC ranged from 9.48 +/- 2.91 to 11.1
      +/- 3.5 x 10(3)/microliter, while it was 21.7 x 10(3)/microliter in a case of
      meningitis. ESR values in sick buffaloes varied from 57 to 111 mm in the first
      hour.

PMID- 9151409
TI  - Bovine cells infected in vivo with Theileria annulata express CD11b, the C3bi
      complement receptor.
AB  - Bovine cells from cattle infected with Theileria annulata were phenotyped with
      monoclonal antibodies recognizing bovine leukocyte antigens. Macroschizont
      infected, transformed cell lines prepared from peripheral blood mononuclear cells
      of cattle, infected with sporozoites, were assessed by flow cytometry;
      parasitized cells in tissues from infected cattle were examined by
      immunocytochemical techniques. Co-expression of markers for different cell
      lineages by the cell lines precluded a definite conclusion as to their phenotypic
      origins. For, while the pattern of leukocyte antigens expressed by these in vivo
      derived schizont-infected cells, which included CD11b, was indicative of a
      myeloid origin, the possibility that they were NK cells could not be excluded.
      The monoclonal antibody (MAb) IL-A15, which recognizes CD11b, reacted with a high
      proportion of parasitized cells in sections of tissues from infected cattle at
      all stages of acute disease. Mononuclear cells infected with parasites at all
      stages of differentiation, from macroschizont to microschizont, expressed CD11b.
      Such parasitized cells occurred throughout the lymphoid tissues, being found in
      the thymus, spleen and lymph nodes, particularly the prescapular node draining
      the site of infection, the hepatic, mesenteric and precrural nodes, as well as in
      the reticulo-endothelial tissue of the liver, kidney, lung, abomasum, adrenal and
      pituitary glands. These observations provided the first evidence for a myeloid
      origin for the parasitized T. annulata cells found in infected bovine tissues and
      blood and suggested a mechanism whereby schizonts could transfer from cell to
      cell during mechanical infection with schizont-infected cells.

PMID- 9151411
TI  - The effects of the method of calculation on the evaluation of the pharmacokinetic
      parameters of oxytetracycline after intravenous administration to calves.
AB  - The aim of this study was to assess the differences in the values of the
      pharmacokinetic parameters attributable to the use of either linear or nonlinear
      regression analysis and to find the effect of weighting schemes on these
      differences. Six calves received 20 mg/kg oxytetracycline i.v. Blood samples were
      drawn during 72 h. The assay of the drug was performed microbiologically. A
      bicompartmental pharmacokinetic model was used, kinetic analysis being carried
      out by linear regression (LR) and by weighted least-squares nonlinear regression
      (WLSNLR). Statistical analysis included a test for normality, the Kruskall-Wallis
      test and ANOVA with log transformation. The A0, alpha and B0 did not show any
      statistically significant differences attributable to the mathematical method
      used. On the other hand, the statistically significant differences in the beta
      values found using the Kruskall-Wallis test and ANOVA with log transformation
      could be attributed to the different methods employed. ANOVA with log
      transformation determined statistically significant differences between the
      parameters obtained by linear analysis and those obtained by WLSNLR when the
      weighting (w) was 1. When weights were 1/x, 1/x2 or 1/square root of x, no
      statistically significant differences were found. The optimal weighting scheme
      was w = 1/x2 because of a more homogeneous scatter and random distribution of
      residuals about the abcissa axis in a plot of weighted residuals in the ordinate
      versus time in the abcissa. It was concluded that the use of these different
      procedures can give major variations in the apparent value of beta, the most
      important pharmacokinetic parameter. The correct selection of the weighting
      procedure is therefore fundamental in obtaining the best estimate of this
      pharmacokinetic parameter in WLSNLR.

PMID- 9151412
TI  - Some pharmacokinetic parameters of oxfendazole in sheep.

PMID- 9151414
TI  - Human arm stiffness and equilibrium-point trajectory during multi-joint movement.
AB  - By using a newly designed high-performance manipulandum and a new estimation
      algorithm, we measured human multi-joint arm stiffness parameters during multi
      joint point-to-point movements on a horizontal plane. This manipulandum allows us
      to apply a sufficient perturbation to subject's arm within a brief period during
      movement. Arm stiffness parameters were reliably estimated using a new algorithm,
      in which all unknown structural parameters could be estimated independent of arm
      posture (i.e., constant values under any arm posture). Arm stiffness during
      transverse movement was considerably greater than that during corresponding
      posture, but not during a longitudinal movement. Although the ratios of elbow,
      shoulder, and double-joint stiffness were varied in time, the orientation of
      stiffness ellipses during the movement did not change much. Equilibrium-point
      trajectories that were predicted from measured stiffness parameters and actual
      trajectories were slightly sinusoidally curved in Cartesian space and their
      velocity profiles were quite different from the velocity profiles of actual hand
      trajectories. This result contradicts the hypothesis that the brain does not take
      the dynamics into account in movement control depending on the neuromuscular
      servo mechanism; rather, it implies that the brain needs to acquire some internal
      models of controlled objects.

PMID- 9151413
TI  - The characterization of infectious bursal disease virus strains/isolates from
      field outbreaks in India.
AB  - Three infectious bursal disease virus (IBDV) isolates were adapted to culture in
      chick embryo fibroblast cells in which they produced a cytopathic effect. The
      isolates were identified as IBDV by virus neutralization tests using a standard
      hyperimmune serum against infectious bursal disease, physicochemical properties
      and their pathogenicity in chick embryos and chicks. The IBDV S394 strain was
      antigenically different from IBDV S194/IBDV S494 as well as from the IBDV
      Intermediate Georgia strain, one of the vaccine strains in use in India.

PMID- 9151415
TI  - The role of the plant properties in point-to-point arm movements: a robustness
      study.
AB  - In recent papers we demonstrated by means of a modeling study that the smoothness
      of hand paths and the bell-shaped character of hand velocity profiles which have
      been experimentally observed in point-to-point arm movements can be largely
      attributed to the biomechanical properties of the arm rather than to specific
      planning by the central nervous system. In this paper we present a study of the
      robustness of our earlier results comprising two goals: (i) the determination of
      the range of model parameters for which such observations remain valid, (ii) the
      identification of possible relationships between model parameters and kinematic
      variables. The results of this study imply three conclusions: (i) the valid range
      of the tested model parameters (namely the main muscle parameters) is large, (ii)
      the modeled phenomena are well behaved in that parametric changes do not give
      rise to bifurcations or other behavioral discontinuities in the analyzed ranges,
      (iii) there exist precise relationships between certain muscle parameters and the
      time course of the hand velocity. These results point out that the phenomena
      observed in our previous work are indeed robust and can lead to useful insights
      into the mechanisms comprising the regulatory action of the central nervous
      system as well as into the design principles for biologically inspired artificial
      arms.

PMID- 9151416
TI  - EEG simulation: variation of spectral envelope, pulse synchrony and approximately
      40 Hz oscillation.
AB  - Macroscopic EEG travelling wave phenomena and cortical pulse synchronisation
      effects are related within a single simple simulation. Non-specific activation
      acts to control the transfer function of the simulated cortex, and thus
      determines the relative amplitude of macroscopic EEG waves generated by rhythmic
      inputs. When concurrent asynchronous excitatory inputs to separate, local,
      cortical sites are introduced, the simulation reproduces both gamma-band (40 Hz)
      electrocorticogram (ECoG) activity and synchronous oscillation of action
      potential pulse density at the separate sites. The gamma-band ECoG and pulse
      synchrony effects depend on different mechanisms: the former upon local
      excitatory/inhibitory interactions, and the latter on corticocortical
      interactions. The pattern of synchronous activity depends upon both structural
      and dynamic aspects of gain, and is sustained by linearised versions of the
      simulation's state equations. Dynamic properties of the simulation, which are
      independent of scale, describe both microscopic and macroscopic phenomena, all in
      accord with physiological findings.

PMID- 9151417
TI  - Nested reentrant and recurrent computation in early vision: a Bayesian
      neuromorphic model applied to hyperacuity.
AB  - Hyperacuity is demonstrated in a neuromorphic model of the early visual system.
      The model incorporates Bayesian principles which are embodied in the dynamics of
      reentrant and recurrent feedback processes. Each retinotopically mapped area in
      the model represents a transformation of data from the visual field. Sensory
      information propagates in a bottom-up direction from one area to the next, while
      information based on Bayesian priors propagates in a top-down direction through
      reentrant connections. The 'bottom-up' and 'top-down' information maintain a
      separate existence in distinct layers of the model, but they interact through
      local connections within each area. Transformations between one area and the next
      are defined by the reentrant synaptic connections between areas, while local
      prior probability maps are defined by local recurrent connections within layers.
      The representation of hyperacuity is accomplished using a model of functional
      multiplicity: the large ratio of neurons in striate cortex compared with the
      number of afferent fibers projecting from the lateral geniculate nucleus. High
      functional multiplicity, in conjunction with hierarchical reentrant processing,
      allows the model to represent a fine-grained restoration of the line structure of
      visual input.

PMID- 9151418
TI  - On Hebbian-like adaptation in heart muscle: a proposal for 'cardiac memory'.
AB  - Studies on the effects of external pacing of heart suggest that the organ, like
      the nervous system, possesses the properties of 'memory' and adaptation. Changes
      induced in cardiac activation patterns persist long after the agent that induced
      those changes itself is removed. After the effects of stimulation have
      disappeared, response to the stimulus applied for a second time is much greater
      than the earlier response. Motivated by such results, this paper further explores
      the possibility of a 'cardiac memory'. In particular, we point out that
      communication via gap junctions in cardiac tissue is similar to synaptic
      conductance in nervous tissue and demonstrate, with the aid of a mathematical
      model, that cardiac tissue can exhibit memory-like behavior if gap-junctional
      conductances are allowed to adapt according to a Hebbian-like mechanism.

PMID- 9151419
TI  - Parallel processing by a homogeneous group of coupled model neurons can enhance,
      reduce and generate signal correlations.
AB  - Correlated activities have been proposed as correlates of flexible association
      and assembly coding. We addressed the basic question of how signal correlations
      on parallel pathways are enhanced, reduced and generated by homogeneous groups of
      coupled neurons, and how this depends on the input activities and their
      interactions with internal coupling processes. For this we simulated a fully
      connected group of identical impulse-coded neurons with dynamic input and
      threshold processes and additive or multiplicative lateral coupling. Input
      signals were Gaussian white noise (GWN), completely independent or partially
      correlated on a subgroup of the parallel inputs. We show that in states of high
      average spike rates input-output correlations were weak while the network could
      generate correlated activities of stochastic, oscillatory and rhythmic bursting
      types depending exclusively on lateral coupling strength. In states of low
      average spike rates input-output correlations were high and the network could
      effectively enhance or reduce differences in spatial correlation applied to its
      parallel inputs. The correlation differences were more pronounced with
      multiplicative lateral coupling than with the additive interactions commonly
      used. As the different modes of correlation processing emerged already by global
      changes in the average spike rate and lateral coupling strength, we assume that
      in real cortical circuits changes in correlational processing may also be induced
      by unspecific modulations of activation and lateral coupling.

PMID- 9151420
TI  - Analysis of phase-locking is informative for studying event-related EEG activity.
AB  - A new method is presented for quantitative evaluation of single-sweep phase and
      amplitude electro-encephalogram (EEG) characteristics that is a more informative
      approach in comparison with conventional signal averaging. In the averaged
      potential, phase-locking and amplitude effects of the EEG response cannot be
      separated. To overcome this problem, single-trial EEG sweeps are decomposed into
      separate presentations of their phase relationships and amplitude
      characteristics. The stability of the phase-coupling to stimulus is then
      evaluated independently by analyzing the single-sweep phase presentations. The
      method has the following advantages: information about stability of the phase
      locking can be used to assess event-related oscillatory activity; the method
      permits evaluation of the timing of event-related phase-locking; and a global
      assessment and comparison of the phase-locking of ensembles of single sweeps
      elicited in different processing conditions is possible. The method was employed
      to study auditory alpha and theta responses in young and middle-aged adults. The
      results showed that whereas amplitudes of frequency responses tended to decrease,
      the phase-locking increased significantly with age. The synchronization with
      stimulus (phase-locking) was the only parameter reliably to differentiate the
      brain responses of the two age groups, as well as to reveal specific age-related
      changes in frontal evoked alpha activity. Thus, the present approach can be used
      to evaluate dynamic brain processes more precisely.

PMID- 9151421
TI  - Optimization of catalase biosynthesis in submerged cultures of Aspergillus niger
      mutant.
AB  - The effect of some medium components, viscous substances and metabolic
      inhibitors, on catalase production by mutant Aspergillus niger has been studied
      in shake culture. Altering the composition of the basal medium, particularly
      substituting NaNO3 for KNO3, and peptone for yeast extract brought an increase in
      extra- and intracellular catalase activity by 1.5- and 3-fold, respectively. The
      addition of 2.0-6.0 mg sodium alginate or pectin/ml as viscous additive to the
      medium, containing glucose as carbon source, increased the medium viscosity and
      catalase production in shake culture by about 2.8- to 3.0-fold. The highest yield
      of extracellular catalase activity of A. niger was obtained in the presence of
      sodium orthovanadate and Triton X-100, which improved the activity of this enzyme
      by about 1.5-2.2-fold. A significant increase in intracellular catalase activity
      was observed in the presence of hematin, Tween 80 and sodium orthovanadate (1.7-,
      1.6- and 1.4-fold respectively). The time course of growth and enzyme production
      by A. niger in the optimized medium is also reported.

PMID- 9151422
TI  - Characterization of cellulase complex of Streptomyces albaduncus.
AB  - Exoglucanase and endoglucanase (glucanases) enzymes of S. albaduncus were found
      to be very stable, showing only 36% and 8% loss in activities respectively after
      3 days of incubation at 50 degrees C. In contrast, beta-glucosidase was
      significantly less stable retaining only 22.30% activity after 30 min incubation
      at 40 degrees C. The glucanases manifested maximum stability in pH range of 5.5
      6.0 whereas beta-glucosidase was completely stable over a broad pH range of 6.5
      9.0. Both glucanases were enhanced by some cations whereas beta-glucosidase did
      not require any cation for activity. K(m) values for crude exoglucanase,
      endoglucanase and beta-glucosidase were 40.00 mg/ml, 92.30 mg/ml and 1.714 mM
      with maximum reaction velocities (Vmax) of 0.606, 33.330 and 0.109 IU/mg of
      protein, respectively. The enzymes were subject to end-product inhibition, with
      exo- and endo-glucanases decreasing by 20% and 70% respectively, in the presence
      of 0.3% glucose. However, beta-glucosidase showed marked resistance to glucose
      inhibition, retaining 59% of residual activity even in the presence of 30%
      glucose in the reaction mixture. This characteristic may be advantageous in the
      commercial exploitation of enzyme system. An activation of beta-glucosidase at
      lower concentrations of glucose suggests competitive inhibition.

PMID- 9151423
TI  - The metabolism of gluconate in Escherichia coli. The subsidiary system and the
      nature of the gntS gene.
AB  - The transport and phosphorylation of gluconate in E. coli occurs through two
      systems (GntI and GntII) which duplicate activities. bioH-asd deletion mutants do
      not grow on media with gluconate as sole carbon source because they lack the GntI
      system and do not express GntII. Although E. coli c177 is a delta (bioH-asd)
      mutant, it carries the pyrB linked mutation gnt177 that enables it to metabolize
      this substrate through inducible expression of the GntII system. Several gntS
      derivatives which are unable to grow on gluconate were isolated from E. coli C177
      by spontaneous curing of the transposon Tn10 previously inserted at the gntS
      locus (zjf::Tn10, min 95.3). A representative gntS mutant, E. coli TI141A
      retained the ability to take up gluconate but had lost the thermosensitive
      gluconokinase activity (gene gntV, min 96.9). Furthermore, it could be
      demonstrated that gntV is repressed in E. coli TI141A. The results indicate that
      gntS might specify a trans-acting positive regulator involved in the control of
      at least the expression of the thermosensitive gluconokinase (GntII), instead of
      a gluconate uptake system as it was previously postulated. Likewise, these
      results can be used to reconsider whether the locus altered by the gnt177 lesion
      is allelic with that of the GntII permease instead of a regulator, as it was
      originally postulated.

PMID- 9151425
TI  - Diversity within bacterial isolates hybridizing with Comamonas probe ppT.
AB  - Diversity within bacteria isolated from activated sludge and the Baltic sea and
      recognized by the rRNA targeted oligonucleotide probe ppT (designed by BRAUN
      HOWLAND et al., 1993 to recognize C. testosteroni) was studied. The partial
      nucleotide sequences of 16S genes of the isolates revealed that the activated
      sludge and Baltic sea isolates each formed a separate group distinct from C.
      testosteroni. The analysis of phage and bacteriocin sensitivity as well as whole
      cell protein patterns revealed the same grouping, but in these characters also
      intragroup variation was observed. As a conclusion, neither of the studied groups
      were C. testosteroni, but they probably belong to two previously unknown species
      common in activated sludge or the Baltic sea.

PMID- 9151424
TI  - Localization of alanyl aminopeptidase and leucyl aminopeptidase in cells of
      Pseudomonas aeruginosa by application of different methods for periplasm release.
AB  - Various methods for the isolation of periplasm were examined and compared with
      regard to the complete release of known periplasmic marker enzymes and the
      contamination of the periplasm by cytosol for Pseudomonas aeruginosa PAO1 as a
      significant Gram-negative test strain. The aim of the investigations was to
      clarify the exact localization of alanyl aminopeptidase (AAP) and leucyl
      aminopeptidase (LAP) of this microorganism and to evaluate these methods. The
      osmotic shock of NOSSAL and HEPPEL (1996) was the most effective method with the
      lowest contamination by the cytosolic marker enzyme malic enzyme, but some
      proteins, which are located near the inner side of the cytoplasmic membrane, can
      be released additionally into the periplasm. All other procedures like chloroform
      or polymyxin treatment, the magnesium chloride washing of intact bacteria and
      spheroblasting by lysozyme in the presence of EDTA or magnesium chloride resulted
      only in a partial, sometimes only very low release of periplasm. The periplasmic
      enzymes are bound either more by hydrophobic or more by ionic interactions to the
      cell envelope and show a different behaviour with the different releasing agents.
      These methods are useful for a further differentiation between really periplasmic
      protein, and those proteins, which were false positive found in periplasm as a
      result of the osmotic shock. Our results show that AAP from Pseudomonas
      aeruginosa is a periplasmic enzyme with hydrophobic interactions to the
      cytoplasmic membrane, corresponding to the early results of LAZDUNSKI and MURGIER
      for Escherichia coli (LAZDUNSKI et al. 1975a and b, MURGIER et al. 1977), and LAP
      is cytosolic, but located near the cytoplasmic membrane. The AAP is not a real
      amphipatic membrane protein, as could be demonstrated by phase separation
      experiments with Triton X-114.

PMID- 9151426
TI  - Evidence for and characterization of cytochrome P-450 in Neurospora crassa.
AB  - Cytochrome P-450 was detected in microsomes and presumably in cytosol of
      Neurospora crassa, and was found to be inducible by progesterone. In the
      microsomal fraction cytochrome b5 and NADPH-cytochrome c reductase activities
      were measurable, too. Cytochrome P-450 of Neurospora crassa is inhibited by SKF
      525 A and by inhibitors of ergosterol biosynthesis. After induction of cytochrome
      P-450 with progesterone 11 alpha-hydroxyprogesterone as one metabolite of
      progesterone was detected in the culture media as well as in the mycelia. After
      42 hours about 70% of progesterone were metabolized.

PMID- 9151427
TI  - Effects of haemoglobin O2 saturation on volume regulation in adrenergically
      stimulated red blood cells from the trout, Oncorhynchus mykiss.
AB  - Adrenergic stimulation of trout red blood cells activates a Na+/H(+)-exchange. If
      unopposed, the ensuing increase in cell Na+ leads to an isosmotic cell swelling.
      In this study the effect of the level of haemoglobin O2 saturation on volume
      regulation has been investigated in adrenergically stimulated red blood cells
      from trout: at full haemoglobin O2 saturation, net influx of Na+ through the
      Na+/H(+)-exchanger was balanced by net efflux of K+ and no increases in cell
      volume took place. In contrast, at low O2 saturation (8-14%) adrenergic
      stimulation led to a substantial increase in cell Na+, K+ and volume. Moreover,
      cell volume recovery after adrenergic swelling was incomplete at low O2
      saturation, whereas cells at high O2 saturation exhibited a fast and complete
      cell volume recovery. In cells exposed to alternating high and low O2 saturation,
      volume regulation was similar to the regulation found in cells maintained at high
      O2 saturation. In cells at high O2 saturation, extrusion of cellular Na+ by the
      Na+/K(+)-pump significantly contributed to the volume decrease. It is concluded
      that trout red blood cells at high or alternating O2 saturations possess a
      powerful regulatory volume decrease response that is shut off at low O2
      saturation. The physiological implications of this regulation is discussed.

PMID- 9151428
TI  - Phenotypic variation in seasonal adjustments of testis size, body weight, and
      food intake in deer mice: role of pineal function and ambient temperature.
AB  - We investigated pineal function as well as reproductive and energetic
      characteristics in male deer mice (Peromyscus maniculatus) that differentially
      respond to short photoperiod with full, partial or no gonadal regression. In mice
      at both high (23 degrees C) and low temperature (1 degree C), these phenotypic
      differences in reproductive responses to short days were not reflected by
      differences in urinary excretion of 6-sulphatoxy-melatonin, the main metabolite
      of pineal melatonin. Neither duration nor amplitude or phase-angle of nocturnal
      peaks in 6-sulphatoxymelatonin significantly differed between reproductive
      phenotypes at either temperature. Differences in testis size were, however,
      associated with different energy requirements. In gonadally regressed males only,
      food intake and body weight were significantly (P < 0.01) reduced by up to 29%
      and 13% respectively. Chronic cold exposure (5 degrees C) had no effect on the
      proportion of males undergoing testicular regression under short days, but caused
      a general elevation in body weights among all mice (P < 0.05). Phenotypic
      differences in body weight and food intake were maintained in the cold. Together,
      these results suggest that within-population variation of reproductive responses
      in male deer mice is based on post-pineal differences in the regulation of
      gonadal function, and that phenotypic characteristics in reproductive and
      energetic responses to short days are largely unaffected by ambient temperature.

PMID- 9151429
TI  - Endotoxin-challenges precocial neonates and iron changes.
AB  - In adult mammals fever is associated with the reduction of blood plasma iron
      level. Immature mammals, however, show either a decrease (precocial animals such
      as guinea pig neonates) or a lack of reduction (altricial animals such as human
      neonates) of plasma iron in response to endotoxin. In order to determine whether
      this difference is connected with maturity just after delivery, plasma iron
      concentration, hematocrit, body temperature and body mass were measured in rat
      pups injected with E. coli endotoxin in doses of 50 or 200 micrograms kg-1. Rat
      pups, like human neonates, are altricial animals. In 7-day-old rats injection of
      LPS led to a dose-dependent decrease in plasma iron level. The fall in plasma
      iron was accompanied by changes in body temperature and body mass. The results
      showed that plasma iron response to endotoxin in altricial rat neonates is
      similar to that observed in precocial guinea pig pups.

PMID- 9151430
TI  - The effect of exercise and restraint on pectoral muscle metabolism in pigeons.
AB  - The effect of various activity regimes on metabolism of pigeon pectoralis was
      examined by measurement of blood lactate following exercise, total lactate
      dehydrogenase activity of pectoral muscle, and proportions of specific isoenzymes
      of pectoral muscle lactate dehydrogenase. Sprint-trained birds had the highest
      pectoral muscle lactate dehydrogenase activity (1409 IU.g-1 wet tissue), while
      endurance-trained birds had the highest peak lactate levels (287 mg.dl-1, extra
      polated from decay curves) and fastest half-time of the lactate response (4.8
      min) following exercise, but the lowest lactate dehydrogenase activity (115 IU.g
      1 wet tissue). Immobilization of one wing for 3 weeks following endurance
      training produced a marked increase in lactate dehydrogenase activity of the
      immobilized muscle, compared to that in the contralateral pectoralis and
      endurance-trained muscle. Aerobic forms of the lactate dehydrogenase enzyme (that
      favor conversion of lactate to pyruvate) predominated in pectoral muscle of
      endurance-trained birds, while cage-confined birds exhibited primarily the
      anaerobic isoenzymes. These results demonstrate that conversion of pectoral
      muscle lactate dehydrogenase isoenzymes, total lactate dehydrogenase activity,
      and half-time of lactate response after exercise is dependent on activity regime
      in pigeons. In this respect, pigeon pectoral muscle responds to training and
      disuse in a manner similar to that of mammalian skeletal muscle.

PMID- 9151431
TI  - Na(+)-dependent Ca2+ uptake in isolated opercular epithelium of Fundulus
      heteroclitus.
AB  - It is concluded that Ca2+ transport across the basolateral membranes of the
      ionocytes in killifish skin is mediated for the major part by a Na+/Ca(2+)
      exchange mechanism that is driven by the (transmembrane) Na+ gradient established
      by Na+/K(+)-ATPase. The conclusion is based, firstly, on the biochemical evidence
      for the presence of a Na+/Ca(2+)-exchanger next to the Ca(2+)-ATPase in the
      basolateral membranes of killifish gill cells. Secondly, the transcellular Ca2+
      uptake measured in an Ussing chamber setup was 85% and 80% reduced in freshwater
      (FW) and SW (SW) opercular membranes, respectively, as the Na+ gradient across
      the basolateral membrane was directly or indirectly (by ouabain) reduced.
      Thapsigargin or dibutyryl-cAMP/IBMX in SW opercular membranes reduced Ca2+ influx
      to 46%, comparable to the effects seen in FW membranes [reduction to 56%;
      Marshall et al. 1995a]. Basal Ca2+ influx across the opercular membrane was 48%
      lower in membranes from fish adapted to SW than in membranes from fish adapted to
      FW. Branchial Na+/K(+)-ATPase activity was two times higher in SW adapted fish.

PMID- 9151433
TI  - Seasonal variation in the resting metabolic rate of male wood mice Apodemus
      sylvaticus from two contrasting habitats 15 km apart.
AB  - Diurnal and nocturnal resting metabolic rates of winter- and summer-acclimatized
      adult male wood mice Apodemus sylvaticus from two adjacent populations, 15 km
      apart, were measured. One population lived in deciduous woodland, and experienced
      a narrower daily range of temperatures than the second population, which
      inhabited maritime sand-dunes. Ambient temperature and body mass had significant
      effects on the resting metabolism of mice, excluding winter-acclimatized sand
      dune animals where only temperature explained significant amounts of the observed
      variation. Only in this latter group could a thermoneutral zone be determined,
      with a lower critical temperature of ca. 25 degrees C and resting metabolism of
      0.155 W. Nocturnal resting metabolic rates were significantly greater than
      diurnal levels. Winter acclimatization was associated with reductions in thermal
      conductance and resting metabolism, thus minimizing energy expenditure at rest.
      Site differences in thermoregulatory strategies were only found in winter,
      thermal conductances remained similar but mice from the sand-dunes had
      significantly lower metabolic rates than those from the woodland. Winter
      acclimatization in wood mice was influenced by factors in addition to
      photoperiod. Intra-specific and individual variations in resting metabolism, as
      shown in this study, potentially have a pronounced effect on the daily energy
      expenditure of a free-living animal.

PMID- 9151432
TI  - Effect of constant and fluctuating temperature on daily melatonin production by
      eyecups from Rana perezi.
AB  - We analysed the effect of daily temperature cycles in relation to constant
      temperature on day/night melatonin synthesis in frog eyecups in culture. Eyecups
      were cultured for 24 h under 12L:12D photoperiod and two thermal regimes,
      constant temperature (25, 15 and 5 degrees C) and thermoperiod (WL/CD,
      thermophase coinciding with photophase and cryophase coinciding with scotophase;
      and CL/WD, cryophase coinciding with photophase and thermophase coinciding with
      scotophase). A negative correlation between ocular serotonin N-acetyltransferase
      activity and culture temperature for both diurnal and nocturnal activities has
      been observed. This effect of increased ocular activity at low temperature is
      more pronounced than the well-known stimulatory effect of darkness, and it does
      not depend on the photoperiod phase. The lack of interactions between the phase
      of photoperiod and culture temperature indicates that the effects of both factors
      are independent. Night-time temperature is the key factor in determining the
      amplitude of the melatonin rhythm in the Rana perezi retina. However, daytime
      temperature can not counteract the inhibitory effect of light on ocular melatonin
      synthesis.

PMID- 9151434
TI  - Lead poisoning of children in Africa, II. Kwazulu/Natal, South Africa.
AB  - The prevalence of elevated blood lead (PbB) levels in rural and semi-urban areas
      of Kwazulu/Natal (KZN) as well as the risk factors for elevation of PbB among
      children in informal settlements are examined. The study involved over 1200
      children in two age groups: 3-5 and 8-10 years old. Average PbB level in Besters,
      an informal settlement in the Durban metropolitan region, was 10 micrograms/dl
      with 5% of the children showing PbB level of greater than 25 micrograms/dl. By
      comparison, average PbB value in Vulamehlo, a rural area located 90-120 km from
      Durban, was 3.8 micrograms/dl and 2% of the PbB was greater than 10
      micrograms/dl. The results show that many children in KZN are at risk of being
      lead poisoned. Household factors that were significantly associated with PbB
      levels in children included distance from tarred roads, overcrowding, hygienic
      habits in the household and the burning of solid wastes for heating or cooking.
      Lack of significant association with child risk behaviors is attributed to the
      over-riding influence of high levels of contaminated dusts both indoor and
      outdoor. With recent introduction of unleaded gasoline in South Africa, a number
      of unique socio-ecological factors are expected to slow the change in PbB levels
      of children in some townships.

PMID- 9151435
TI  - Lead poisoning of children in Africa, III. Kaduna, Nigeria.
AB  - This study investigated the prevalence of elevated blood lead (PbB) levels in
      children 1-6 years old in Kaduna, a medium size city in northern Nigeria. Mean
      PbB was found to be 10.6 micrograms/dl, and 2% of the children had PbB levels
      greater than 30 micrograms/dl. Highest average PbB levels were found in children
      5 years old and was attributed to the tendency for this age group to play longer
      in contaminated outdoor environments. The strongest associations were found
      between PbB and whether the family owned a car or lived in a house on a tarred
      road. Potential sources of lead in the city as well as household and behavior
      risk factors likely to result in exposure of children to lead are discussed. This
      study provides additional data pointing to childhood lead poisoning as being a
      major public health problem in urban areas of Africa.

PMID- 9151436
TI  - Baseline studies in the Slave River, NWT, 1990-1994: Part II. Body burden
      contaminants in whole fish tissue and livers.
AB  - The Northwest Territories section of the Slave River is the recipient of chemical
      compounds from a variety of sources, including upstream industry and agriculture.
      In 1990, concerned government agencies formulated a practical, focussed, and
      comprehensive environmental monitoring program to assess contamination in the
      river and the Slave River Environmental Quality Monitoring Program was
      established. The program was designed to respond to the distinct requirements of
      two major monitoring goals. The first priority was to ascertain whether the fish
      in the Slave River were safe to eat. The second goal was to establish a baseline
      data set with which to compare future effects from upstream activities and long
      range transport of contaminants. From the data gathered in the present study, it
      appears that whole tissue of fish (muscle) is fit for human consumption.
      Throughout the monitoring period, consistently low concentrations of
      organochlorine pesticides, PCBs, dioxin and furan isomers, PAHs, chlorinated
      phenolics, and heavy metals have been observed and median concentrations have all
      been below federal fish consumption advisories. Also, the numerous data values
      below analytical detection limits attest to the relatively uncontaminated nature
      of the fish. These results were comparable with other studies conducted on arctic
      animals. The heavy metals observed in fish tissue are probably of natural
      origins, since inorganic analyses of suspended sediment in the Slave River
      indicated relatively elevated levels, with no known anthropogenic source. While
      the present study concluded that contaminant levels in whole fish are low,
      toxaphene levels in burbot livers should continue to be monitored since
      concentrations were consistently above fish consumption advisories during the
      monitoring and are eaten extensively by the native peoples. The second goal of
      the monitoring program was to develop a baseline data set and the values tabled
      in the current paper are useful in establishing a foundation for future
      comparison.

PMID- 9151437
TI  - Land application of sewage sludge in China.
AB  - Land application of sewage sludge in China is thoroughly reviewed. Operation of
      sewage sludge disposal is usually expensive and/or easy to contaminate the
      environment. In China, most sewage sludge has not been treated and disposed of
      properly, resulting in environmental pollution and potential exposure to humans.
      In the near future, sewage sludge production in China will increase rapidly
      together with the dramatic increase of municipal wastewater treatment ratio
      (treated/produced), implying that the problem of sewage sludge disposal will
      become more serious and unavoidable. Proper land utilization of stabilized sewage
      sludge can make a positive contribution to agriculture, forestry, horticulture
      and city development. Heavy metals, organic pollutants and pathogens concentrated
      in sewage sludge during wastewater treatment are the main obstacles to land
      application of sewage sludge. To promote land application of sewage sludge in
      China, a statewide survey of sewage sludge production and harmful components in
      sewage sludge should be carried out. Sewage sludge management and technologies
      for sludge treatment and disposal suitable to Chinese conditions should be paid
      more attention.

PMID- 9151438
TI  - Accumulation of copper, nickel, lead and zinc by snail, Lunella coronatus and
      pearl oyster, Pinctada radiata from the Kuwait coast before and after the Gulf
      War oil spill.
AB  - This study investigated the contribution of the 1991 oil spill to heavy metal
      contamination in the marine environment of the Gulf in Kuwait by analyzing
      moleskin organisms (gastropod snail, Lunella coronatus and bivalve Pearl oyster,
      Pinctada radiata) for their heavy metal contents before and after the spill.
      Concentrations of copper (Cu), nickel (Ni), lead (Pb) and zinc (Zn) were
      determined in the soft tissue of both snail and oyster samples from three coastal
      stations during 1990 and 1994. In the 1990 samples, the metal concentrations in
      snail and oysters from different sampling stations were between 0.35 and 0.67;
      0.11 and 2.29 micrograms/g for Cu, 1.50 and 4.50; 0.47 and 1.33 micrograms/g for
      Ni, 0.16 and 2.98; 0.44 and 0.69 microgram/g for Pb and 19.94 and 54.79; 247.20
      and 1204.40 micrograms/g for Zn, respectively. In the 1994 samples, the metal
      concentrations were between 11.24 and 55.00; 28.90 and 168.43 micrograms/g for
      Cu, 15.33 and 16.96; 0.08 and 1.54 micrograms/g for Ni, 0.37 and 0.57
      microgram/g; 0.07 and 0.44 microgram/g for Pb and 28.86 and 486.61; 17.75 and
      575.00 micrograms/g for Zn respectively. The 1994 samples have significantly
      higher mean concentrations of Cu, Ni and Zn than the 1990 samples, except Pb in
      the 1994 samples, which showed a slightly lower mean concentration. The
      difference in patterns of metal occurrence and the significant increase in the
      Cu, Ni, and Zn concentrations in the 1994 snail and oyster samples were due to a
      contribution from the 1991 Gulf War oil spill.

PMID- 9151439
TI  - Extraction of lead, cadmium and zinc from overglaze decorations on ceramic
      dinnerware by acidic and basic food substances.
AB  - Dinnerware decorated with overglaze designs can release toxic metals into food
      substances in amounts high enough to constitute health hazards. When dishes made
      in the US before 1970 were filled with 4% acetic acid for 24 h, lead
      concentrations of up to 610 micrograms/ml and cadmium concentrations of up to 15
      micrograms/ml were measured. Acetic acid leachates from more than half the dishes
      tested for lead (78 of 149) contained levels exceeding the US Food and Drug
      Administration (FDA) allowable concentration of 3.0 micrograms/ml. One-fourth of
      dishes tested for cadmium (26 of 98) exceeded the FDA limit of 0.5 microgram/ml.
      High concentrations of lead, cadmium and zinc were also released into 1%
      solutions of citric and lactic acids. Significant amounts of these metals were
      extracted by basic solutions of sodium citrate and sodium tripolyphosphate, as
      well as by commercial food substances including sauerkraut juice, pickle juice,
      orange juice, and low-lactose milk. Relative concentrations of lead, zinc and
      cadmium released depend on the leaching agent used. Citric acid leachates contain
      higher lead:cadmium and zinc:cadmium (but lower lead:zinc) ratios than do acetic
      acid leachates from nominally identical dishes. Repeated extractions with acetic
      acid show that even after 20 consecutive 24-h leachings many dishes still release
      lead in concentrations exceeding FDA limits.

PMID- 9151440
TI  - Determination of environmental reference concentration of six PAHs in urban areas
      (Pavia, Italy).
AB  - We propose a sampling strategy, using individual dosimetry to measure the daily
      inhaled quantity of PAHs in urban air. The method was applied to monitor 56
      subjects living in an Italian town (Pavia; 80 000 inhabitants) and the
      Environmental Reference Concentration (E.R.C.) of six PAHs (classified as
      'possible' carcinogenic agents for humans) was determined. The individual
      environmental samplings took place in two different seasons (winter and summer),
      for persons living in four different urban areas with different traffic density.
      Subjects were selected using a specific questionnaire designed to collect
      information on indoor and indoor+outdoor exposure times. The mean +/- S.D. value
      of Benzo[a]pyrene [BaP] was 0.37 +/- 0.15 ng m-3 in winter and 0.12 +/- 0.07 ng m
      3 in summer. Assuming 18 m3 as the daily inhaled quantity the estimate of the BaP
      inhaled quantity was 6.66 ng/day in winter and 2.16 ng/day in summer.

PMID- 9151441
TI  - Personal exposure to elements in Mexico City air.
AB  - Personal exposures to various metals in airborne particulates in Mexico City were
      measured over a seven consecutive-day period. Subjects were divided into two
      groups, Group A, whose work required them to spend considerable time outdoors and
      in traffic (messengers, delivery men, taxi drivers, salesmen), and Group B who
      spent most of their time indoors (university professors, consultants, managers
      and research workers). Group A spent 32 +/- 8.5% of their time outdoors, while
      Group B spent 10.7 +/- 6.7% of their time outdoors. Group A had higher exposures
      to airborne lead, zinc, vanadium, manganese and chromium than did Group B. There
      was no difference between the groups with respect to airborne copper exposures.
      Overall exposures to the various airborne metals were: lead, 435 +/- 220 ng m-3;
      zinc, 361 +/- 253 ng m-3; vanadium, 23 +/- 12 ng m-3; manganese, < or = 30 +/- 25
      ng m-3; chromium, < or = 8.5 +/- 5.5 ng m-3; and copper, < or = 45 +/- 32 ng m-3.
      A significant number of samples were below the analytical limits of detection for
      manganese and copper.

PMID- 9151442
TI  - Determination of copper levels in serum of healthy subjects by atomic absorption
      spectrometry.
AB  - Copper levels in serum samples of 84 healthy subjects living in southeastern
      Spain were determined using the flame atomic absorption spectrometry technique.
      Mineralization of samples was carried out with an HNO3/HClO4 (4:1) mixture in a
      thermostated mineralization block. The accuracy of the method was tested by using
      a standard reference material. A mean recovery percentage of 104.70% was
      obtained. The relative standard deviation (R.S.D.) as a measurement of the
      precision of the method was lower than 5% in the concentration range considered.
      Mean copper concentrations were 1.092 +/- 0.365 mg/l (with the range 0.304-2.000
      mg/l) and 1.113 +/- 0.253 mg/l (corresponding to an interval of 0.648-1.760 mg/l)
      for women and men, respectively. There are no significant differences between the
      copper levels in serum according to either sex or geography zone (P > 0.05). For
      example, there were no differences of copper levels in serum of subjects from
      coastal and mountainous zones. Estimated daily dietary intakes on copper in women
      and men were 1.38 and 2.10 mg Cu/day respectively.

PMID- 9151445
TI  - Kinetics of Ca(2+)- and ATP-dependent, voltage-controlled anion conductance in
      the plasma membrane of mesophyll cells of Pisum sativum.
AB  - Whole-cell patch-clamp techniques were used to measure anion currents through the
      plasma membrane of protoplasts of mesophyll cells of expanding pea (Pisum sativum
      L.) leaves. Voltage-induced changes of the currents could be modelled with single
      exponential activation and deactivation kinetics. The anion currents were
      activated at negative membrane potentials. The time constant of activation, tau
      act, increased from 145 ms at -140 mV to 380 ms at -20 mV. A Boltzmann fit to the
      activation curve, n infinity (delta GVm/delta Gmax), yielded a half-activation
      voltage of +27 mV. Opening and closing rate constants, alpha and beta
      respectively, were calculated from the values of tau and n infinity. The currents
      depended on the presence of cytoplasmic Ca2+ concentrations higher than 10(-6) M.
      Including 3 mM MgATP in the intracellular solution resulted in a voltage
      dependent inactivation of the anion current. The conductance-voltage relation
      resulting from the voltage-dependent activation and inactivation had a maximum at
      about -25 mV. The relations of the current in pea are discussed with respect to
      the anion currents in guard cells and suspension-cultured tobacco cells, and its
      possible role in growing leaf cells.

PMID- 9151448
TI  - Interaction of auxin-binding protein 1 with maize coleoptile plasma membranes in
      vitro.
AB  - In a search for membrane "docking proteins" interacting with Zea mays auxin
      binding protein (ABP1) the binding of purified ABP1 to maize coleoptile plasma
      membrane vesicles was investigated. Concentration-dependent, saturable binding of
      ABP1 to the membrane vesicles was observed in binding assays using 10(-8)-10(-6)
      M ABP1. Biotinylated ABP1 was displaced from the membrane binding sites by
      competition with unlabeled ABP1, demonstrating specific binding. The association
      step proved to be pH-dependent with maximum binding at pH 5.0 or lower. Auxins
      did not influence the ABP1 binding to plasma-membrane vesicles, but ABP1
      associated with plasma-membrane vesicles was still able to specifically bind
      [3H]naphthalene-1-acetic acid. The rather stable interaction of ABP1 with plasma
      membrane vesicles was only affected by strong alkaline buffers or detergents. The
      binding capacity was calculated to be in the range of 0.2 pmol ABP1 per g
      coleoptile fresh weight.

PMID- 9151446
TI  - Overexpression of a soybean gene encoding cytosolic glutamine synthetase in
      shoots of transgenic Lotus corniculatus L. plants triggers changes in ammonium
      assimilation and plant development.
AB  - A soybean cytosolic glutamine synthetase gene (GS15) was fused with the
      constitutive 35S cauliflower mosaic virus (CaMV) promoter in order to direct
      overexpression in Lotus corniculatus L. plants. Following transformation with
      Agrobacterium rhizogenes, eight independent Lotus transformants were obtained
      which synthesized additional cytosolic glutamine synthetase (GS) in the shoots.
      To eliminate any interference caused by the T-DNA from the Ri plasmid, three
      primary transformants were crossed with untransformed plants and progeny devoid
      of TL- and TR-DNA sequences were chosen for further analyses. These plants had a
      50-80% increase in total leaf GS activity. Plants were grown under different
      nitrogen regimes (4 or 12 mM NH4+) and aspects of carbon and nitrogen metabolism
      were examined. In roots, an increase in free amino acids and ammonium was
      accompanied by a decrease in soluble carbohydrates in the transgenic plants
      cultivated with 12 mM NH4+ in comparison to the wild type grown under the same
      conditions. Labelling experiments using 15NH4+ were carried out in order to
      monitor the influx of ammonium and its subsequent incorporation into amino acids.
      This experiment showed that both ammonium uptake in the roots and the subsequent
      translocation of amino acids to the shoots was lower in plants overexpressing GS.
      It was concluded that the build up of ammonium and the increase in amino acid
      concentration in the roots was the result of shoot protein degradation. Moreover,
      following three weeks of hydroponic culture early floral development was observed
      in the transformed plants. As all these properties are characteristic of
      senescent plants, these findings suggest that expression of cytosolic GS in the
      shoots may accelerate plant development, leading to early senescence and
      premature flowering when plants are grown on an ammonium-rich medium.

PMID- 9151450
TI  - NopA64, a novel nucleolar phosphoprotein from proliferating onion cells, sharing
      immunological determinants with mammalian nucleolin.
AB  - Five major soluble nuclear proteins associated with cell proliferation were
      identified in Allium cepa L. root cells. One of them, of 64 kDa, was revealed by
      Western blotting with anti-mammalian nucleolin antibodies. A polyclonal antibody
      raised against this protein, which we have named NopA64, localised it in the
      nucleolus as well as in nuclear coiled bodies. Together with NopA64, the antibody
      also revealed a smaller form, called NopA61. Both proteins were present in the
      soluble ribonucleoprotein fraction and in the nuclear matrix of proliferating
      cells, but NopA61 was the only form revealed in differentiated cells. NopA64
      contained epitopes also present in other plants, in mammalian nucleolin and in
      its yeast homologue, gar2. In mammals, the highest homology was with 50-kDa
      nucleolin fragments containing the RNA-binding motifs and the glycine-arginine
      rich (GAR) domain. NopA64 was moderately phosphorylated in vitro by exogenous
      casein kinase II and cdc2 kinase, whereas NopA61 was highly phosphorylated by
      casein kinase II. Furthermore, NopA61 was the only band detected after
      dephosphorylation as well as after endoproteolysis of NopA64. This protein could
      be one of the various functional homologues of mammalian nucleolin in plant
      cells.

PMID- 9151451
TI  - Nitrate reductase activation state in barley roots in relation to the energy and
      carbohydrate status.
AB  - The NADH-dependent nitrate reductase (NR, EC 1.6.6.1) in roots of hydroponically
      grown barley seedlings was extracted, desalted and the activity measured in
      buffer containing either Mg2+ (10 mM) or EDTA (5 mM). The former gives the actual
      NR activity (NRact) equivalent to dephospho-NR, whereas the latter gives the
      maximum NR capacity of the dephospho-form (NRmax). Both values together permit an
      estimation of the NR-phosphorylation state. Changes in NRact and NRmax were
      followed in response to root aeration or to shoot illumination or shoot removal,
      and were correlated with sugar contents and adenylate levels. Ethanol formation
      was also measured in roots differing in NR activity in order to obtain
      information on the relation between anaerobic alcoholic fermentation and nitrate
      reduction. In aerated roots, NR was highly phosphorylated (about 80%) and largely
      inactive. It was partly dephosphorylated (activated) by anoxia or by cellular
      acidification (pH 4.8 plus propionic acid). Anaerobic activation
      (dephosphorylation) of NR was stronger at acidic external pH (5) than at slightly
      alkaline pH (8), although ATP levels decreased and AMP levels increased at pH 5
      and at pH 8 to the same extent. Thus, rapid changes in the NR-phosphorylation
      state in response to anaerobiosis were not directly triggered by the adenylate
      pool, but rather by cytosolic pH. Under prolonged darkness (24 h) or after shoot
      removal. NRmax decreased slowly without a large change in the phosphorylation
      state. This decrease of NRmax was correlated with a large decrease in the sugar
      content, and was prevented by glucose feeding, which had only minor effects on
      the phosphorylation state. Cycloheximide also prevented the decrease in NRmax
      without affecting the phosphorylation state. In contrast, anaerobiosis or
      cellular acidification prevented the decrease of NRmax and at the same time
      decreased the NR-phosphorylation state. It is suggested that NR turnover in roots
      is controlled by several factors: NR synthesis appears to depend on sugar
      availability, which has little effect on the phosphorylation state; in addition,
      NR degradation appears to be strongly affected by the phosphorylation state in
      such a way that the inactive phospho-NR is a better substrate for NR degradation
      than the dephospho-form. The rate of anaerobic ethanol formation was not affected
      by NR activity, indicating that the purpose of NR activation under hypoxia or
      anoxia is not to decrease or prevent alcoholic fermentation.

PMID- 9151452
TI  - Proximal row carpectomy: an alternative to wrist fusion?
AB  - Problems with implant failure and silicone synovitis and a high complication rate
      in wrist arthrodesis have recently increased the interest in solutions that use
      residual biological articular surfaces. These include limited intercarpal fusions
      and proximal row carpectomy (PRC). PRC is a relatively easy procedure with few
      complications. We reviewed 27 personal cases. According to this study PRC offers
      a painless range of motion, with an average of 68 degrees flexion/extension range
      and an average grip strength of 60% of the contralateral side. The failure rate
      is 18.5%. However, failures can be successfully converted into wrist arthrodesis.
      Our follow-up period ranges from 6 to 36 months. Late deterioration has not been
      reported in the literature. On the contrary, improvement of mobility and grip
      strength several months after operation have been observed. We still favor PRC as
      a salvage procedure in order to offer the patient some motion, provided that
      there is no osteoarthritis over the capitate and the lunate facet preoperatively.

PMID- 9151453
TI  - Intraoperative EMG response of the musculature after stimulation of the
      glenohumeral joint capsule.
AB  - In an experimental study we investigated the EMG response in 10 human subjects
      after intraarticular stimulation of the shoulder joint capsule following
      arthroscopic insertion of the stimulating electrode in the anterior glenohumeral
      ligaments. The muscle response was documented by mono- or bipolar electrodes.
      Reproducible EMG response patterns were present in superficial as well as in deep
      muscle layers. The response time ranged from 100 to 516 msec. The earliest muscle
      response was found in the anterior part of the deltoid muscle and the latest one
      in the supraspinatus muscle and the lateral part of the deltoid muscle. CLINICAL
      RELEVANCE: The results of this study suggest a significant influence of the
      tension in the joint capsule on the activity of the stabilizing musculature.

PMID- 9151454
TI  - Skeletal metastases of unknown origin: a retrospective analysis of 29 cases.
AB  - The objective of this study was to assess the diagnostic strategy in identifying
      occult primary carcinomas in metastatic bone disease. The records of 29 patients
      seen between 1983 and 1993 were reviewed retrospectively. The patients had been
      evaluated nonuniformly with a wide array of diagnostic procedures. The primary
      tumor was identified in 22 patients antemortem, and in 2 patients postmortem. In
      5 patients a diagnosis of the primary tumor was never obtained. Eleven of the
      primary tumors were carcinomas of the lung, 3 were prostatic carcinomas, 2 were
      carcinomas of the breast and 2 were malignant lymphomas. In 4 patients
      respectively a carcinoma of the kidney, the pancreas, the ovary or the stomach
      was found. One patient had a carcinoid tumor of the small intestine, and one had
      a retroperitoneal rhabdomyosarcoma. The average survival time after clinical
      onset of skeletal metastases was 12 months. We propose a flow sheet to evaluate
      this category of patients including a medical history, thorough physical
      examination, routine laboratory tests, chest radiography, bone scintigram,
      ultrasonography or computed tomography of the abdomen and biopsy of the most
      accessible metastasis. These tests allowed premortem diagnosis of the primary
      tumor in 75% of the cases. Biopsy should be considered the last test to be
      performed.

PMID- 9151455
TI  - Multiple noncontiguous injuries of the spine in a child: atlantooccipital
      dislocation and seat-belt injury of the lumbar spine.
AB  - Multiple noncontiguous injuries of nonadjoining regions of the spine in children
      are rare. Such injuries can be overlooked as the neurological deficit caused by
      one injury can be masked by the other. The combination of atlantooccipital
      dislocation and a seat-belt injury of the spine in children is rare. We describe
      an unusual case of atlantooccipital dislocation in combination with a seat-belt
      injury of the lumbar spine in a surviving child. Early halo-vest immobilization
      was an effective treatment in this patient. Although survival with
      atlantooccipital injuries is becoming common, severe and persistent neurological
      deficits can result in high morbidity. A brief description of the pathomechanics,
      diagnosis and treatment of the atlantooccipital dislocation and lumbar seat-belt
      injury is given.

PMID- 9151456
TI  - Atlantoaxial rotatory fixation. A case report and proposal of a new
      classification system.
AB  - Atlantoaxial rotatory fixation (AARF) remains a relatively rare finding. A case
      of AARF is reported and the existing Fielding and Hawkins classification is
      reviewed. Furthermore a new classification system is proposed.

PMID- 9151457
TI  - Bilateral stress-fracture of the calcaneal tubercle.
AB  - A case of bilateral stress fracture of the calcaneal tubercle (beak-fractures) in
      a 67-year-old woman is presented. The pathogenesis and treatment are discussed,
      followed by some general considerations on stress fractures.

PMID- 9151458
TI  - Nodular fasciitis of the hallux: difficulties in diagnosis.
AB  - Nodular fasciitis or proliferative fasciitis is currently classified as a tumor
      like hyperplastic lesion of soft tissues. Histological characteristics of this
      lesion have often caused diagnostic problems since it can be mistaken for a
      malignant mesenchymal neoplasm. To highlight this we report a case of nodular
      fasciitis that was difficult to diagnose because of its atypical radiographic and
      clinical features.

PMID- 9151459
TI  - Renal ultrasound mass screening in school children.

PMID- 9151460
TI  - High-frequency oscillatory ventilation--a new management for respiratory distress
      syndrome and intractable respiratory failure.
AB  - High-frequency oscillatory ventilation (HFOV) has been proved to decrease the
      incidence of volutrauma and improve oxygenation and ventilation in severe
      pulmonary diseases by many investigators with animal studies and clinical
      reports, particularly in prematurities with severe respiratory distress syndrome.
      Patients with intractable respiratory failure or air-leak syndrome may be rescued
      by HFOV. During HFOV small volume, less than dead space, is delivered at high
      frequencies. Both inspiration and expiration are active. Oxygenation is mainly
      maintained by mean airway pressure to achieve optimal lung volume. Carbon dioxide
      elimination is mainly controlled by delivered volume. Mean airway pressure,
      fraction of inspiratory oxygen and amplitude are the only three items that need
      frequent adjustments after initial settings. The first two items determine the
      oxygenation and the last one determines ventilation. Careful monitoring of
      conditions the patients, discontinuous learning and cooperation of all coworkers
      are important to use the new therapy. Further studies with long-term follow-up
      are important to assess its appropriate role in different treatment methods and
      different degrees of respiratory diseases.

PMID- 9151462
TI  - Prognostic value of color Doppler echocardiographic findings in premature
      newborns with patent ductus arteriosus.
AB  - This study intended to evaluate the relationship between the prognosis for
      premature newborns (PM) with patient ductus arteriosus (PDA) and their Doppler
      echocardiographic findings. From January 1989 to December 1995, of 369 premature
      newborns in their first postnatal week, 196 underwent ductal evaluations
      echocardiographically: 47 of these 196 cases were found to have PDA. Each
      echocardiogram had complete data for cardiac output, ejection fraction, the left
      atrial-to-the-aortic ratio (LA/AO), the systolic time interval of the right
      ventricle (RVSTI), the transvalvular pressure gradient from tricuspid
      regurgitation (TGTR) and ductal Doppler color flow maps. These 47 premature
      newborns with PDA were grouped into (A) "asymptomatic" patients whose ductus
      closed spontaneously within a one-year follow-up (15 subjects), (B) "symptomatic"
      patients whose ductus were closed by pharmacological or surgical managements (20
      subjects), and (C) "complicated" patients whose ductus caused mortality of the
      host (12 subjects). The remaining 149 premature newborns with a closed ductus
      (CD) served as controls. The RVSTI in these 47 premature newborns with PDA was
      found to be significantly higher than those of 149 CD (0.26 +/- 0.12 vs. 0.18 +/-
      0.06, p < 0.005), and denoting that PM-PDA had a higher mean pulmonary arterial
      pressure. The TGTR of these 47 premature newborns with PDA was also higher than
      these of the 149 CD controls (30.50 +/- 11.85 mmHg vs. 20.54 +/- 6.88 mmHg, p <
      0.005), denoting that PM-PDA had a higher pulmonary arterial systolic pressures.
      Gestational age of group C neonates was younger than group A (29.46 +/- 3.41
      weeks vs. 32.80 +/- 2.78 weeks, P < 0.01). The birth weight of Group C neonates
      was lower than that of Group A (1366.17 +/- 684.28 gm vs. 2061.67 +/- 751.77 gm.
      p < 0.01), therefore, extreme prematurity and small-for-gestational-age could
      have increased the mortality of PM-PDA. Doppler color flow maps of group C showed
      a wider ductal patency, less ductal waist-narrowing, more vehement red-color
      forward flow and less midstream mosaicism. It was concluded that patient with
      extreme prematurity, with very-low-birth-weight or wider patent ductus, higher
      pulmonary hypertension, less midstream mosaicism, or less ductal waist-narrowing
      would have a poorer prognosis.

PMID- 9151461
TI  - Pediatric Wilson's disease: presentation and management.
AB  - Eleven patients (4 males, 7 females) with Wilson's disease who presented before
      18 years of age are described. The mean age onset of symptoms was 11.2 +/- 3.9
      (SD) years. The mean age at diagnosis was 13.3 +/- 3.4 (SD) years. All patients
      had hepatic manifestations of the disease when diagnosed: cirrhosis (6 patients),
      chronic hepatitis (2) and fulminant hepatic failure (3). Three patients were
      asymptomatic at diagnosis. Two of the symptomatic patients presented with new
      undescribed manifestations: one with blurred vision and the other with acalculous
      cholecystitis. At diagnosis, 6 patients had Kayser Fleischer rings and 5 had
      hemolytic anemia. The three patients with fulminant hepatic failure had hemolysis
      with relatively low serum aminotransferase and alkaline phosphatase levels,
      possibly helpful findings for rapid diagnosis of Wilson's disease in such
      presentation. Ten patients were treated with penicillamine. Liver transplantation
      was performed in 4 patients, 2 of which presented with fulminant hepatic failure.
      One patient died while waiting for liver transplantation, the remainder of the
      patients live free of symptoms. It is important to be aware of the different
      manifestations of Wilson's disease in the pediatric population, in order to make
      appropriate evaluations in a timely manner to facilitate early diagnosis and
      appropriate treatment.

PMID- 9151463
TI  - Intravenous immunoglobulin therapy in juvenile dermatomyositis.
AB  - To investigate the effects of intravenous immunoglobulin (IVIG) on patients of
      juvenile dermatomyositis (JDM), seven children with JDM were given monthly IVIG
      in conjunction with other treatments. The indications included disease
      exacerbation, inability to reduce dose of steroid, replacing cytotoxic drug
      because of complication and remission-induction for those with severe initial
      manifestations. Two patients were reported to improve slowly and maintained
      improved status while on a markedly reduced dose of steroid. One patient
      responded favorably to the first three courses only. Three patients had evident
      and quick responses, which could be seen as early as two or three days after the
      infusion. One patient failed to experience any beneficial effect by IVIG. Four
      initial responders had an aggravation some time after discontinuing the monthly
      regimen. The untoward reactions included only two occasions of fever, and another
      two occasions of fever associated with transient proteinuria. In conclusion, IVIG
      may be of value in terms of its quick, pulsatile effect and the adjuvant
      potential to reduce the side effect resulting from exposure to steroid or other
      immunosuppressive agents as well. However, its long-term efficacy is doubtful,
      based on this observation.

PMID- 9151464
TI  - Juvenile nephronophthisis-medullary cystic disease complex: a family study.
AB  - Two sisters, eight and six years old, respectively, were admitted to Mackay
      Memorial Hospital in 1993 with the chief complaints of growth retardation,
      polyuria and nocturnal enuresis. Poor urinary concentration, sodium wasting,
      anemia and renal insufficiency were noted during hospitalization. Ultrasonography
      revealed increased renal echogenicity, loss of corticomedullary differentiation
      and multiple tiny corticomedullary cysts in both kidneys. Renal histopathology
      showed mild increase in glomerular mesangial cellularity and matrix, mild focal
      tubular atrophy with thickening of the tubular basement membrane. Other family
      members were screened by ultrasonography and found another six patients in two
      generations of the paternal side. Renal cysts were found in five cases. Three of
      them had progressively deteriorating renal failure. Five had stable renal
      function after three years of supportive treatment. Thus, it was concluded that
      the age of onset does not differentiate medullary cystic disease (MCD) from
      juvenile nephonophthisis (JN), and that JN and MCD could be considered a clinical
      complex. The absence of corticomedullary cysts on ultrasonography does not
      preclude the diagnosis. It is also suggested that any children with clinical
      symptoms of polyuria, polydipsia, anemia and growth retardation from their early
      years should be carefully examined, and the family history should be investigated
      to permit early detection of the disease.

PMID- 9151465
TI  - Differentiation of Fanconi anemia from aplastic anemia by chromosomal breakage
      test.
AB  - Aplastic anemia (AA) is a disorder of heterogeneous pathogenesis caused by
      diverse etiologies. Fanconi anemia (FA) has the similar features of pancytopenia
      but is characterized by spontaneous or induced chromosomal instability and a
      variety of congenital anomalies. A cytogenetic breakage study is used to enable
      the diagnostic differentiation between FA and the so-called "idiopathic" AA. This
      method is based on the effect of the bifunctional alkylating agent mitomycin C
      (MMC) and alkylating mutagen diepoxybutane (DEB) on the chromosomes of peripheral
      lymphocytes in culture. Among thirty-three new cases of bone marrow failure with
      unknown etiologies, three young male patients were confirmed as victims of FA.
      The methodology and clinical manifestations were discussed. A prenatal screening
      was also performed to exclude the possibility of homozygous FA in one fetus at
      risk. The adequate dose of MMC used in our tests for diagnosis of FA were 20
      ng/mL, while DEB did not work. These findings may suggest genetic diversity or
      other contributing factors in the pathogenesis of FA.

PMID- 9151466
TI  - Magnetic resonance imaging in symptomatic/cryptogenic partial epilepsies of
      infants and children.
AB  - In order to identify the brain lesions of symptomatic/cryptogenic partial
      epilepsies (S/CPEs) in infants and children, magnetic resonance imaging (MRI)
      studies, thorough encephalographic (EEGic) studies, and detailed clinical and
      neurologic evaluations were obtained in 300 infants and children who were
      diagnosed to have S/CPEs with onset before the age of 13 years during the past 7
      years. The overall detection rate of brain lesions by MRI was 41.7% (125/300).
      Congenital malformations (18 cases), vascular malformations (9 cases),
      neurocutaneous syndromes (13 cases), and space-taking lesions (20 cases)
      constitute a large percentage of SPEs in infants and children. A variety of
      insults such as infection, ischemia, hemorrhage, trauma and metabolic disorders
      can result in destructive parenchymal loss lesions including porencephaly, focal
      atrophy, hemiatrophy, and diffuse brain atrophy (20 cases). Major etiologic
      factors leading to infarction, encephalomalacia, leukomalacia, included trauma,
      hvpoxicischemic encephalopathy (HIE), systemic lupus erythematosus (SLE),
      encephalitis, vasculitis, venous thrombosis, vasculopathies, and heart problems
      (22 cases). Mesial temporal sclerosis (MTS) could be evidenced in around 20%
      (18/95) of cases with temporal lobe epilepsy (TLE), which was strongly associated
      with past histories of febrile seizures and encephalitis complicated by status
      epileptics. However, cases with porencephaly, global atrophy or delayed
      myelination of unilateral temporal lobe on MRI were more related to HIE. With the
      advent of neuroimaging techniques, particularly MRI, a wide variety of underlying
      pathology can be detected as a cause of symptomatic partial epilepsies in
      pediatric patients. The occurrence of S/CPE indicates the presence of localized
      brain dysfunction, and many of the causes are potentially treatable. An orderly
      and thorough clinical and laboratory investigations, as well as neuroimaging
      studies should be made to diagnose and treat any underlying conditions.

PMID- 9151467
TI  - High-frequency oscillatory ventilation for infants and children with adult
      respiratory distress syndrome.
AB  - Two infants and two children suffered from severe hypoxemia, presenting as a
      ratio of arterial to alveolar PaO2 < 0.1, persisting for more than 3 hours in
      spite of high settings on conventional mechanical ventilator. Adult respiratory
      distress syndrome was diagnosed with the support of bilateral diffuse haziness on
      chest radiographs. High-frequency oscillatory ventilation with high-lung-volume
      strategy resulted in prompt decrease in oxygenation index and increase in ratio
      of arterial to alveolar P O2 in three (75%) of the 4 patients within 6 hours.
      After a mean duration of 96 hours, high-frequency oscillatory ventilation could
      be weaned off and conventional ventilation could be resumed at lower mean airway
      pressure in 3 patients. They continued to improve and finally recovered. The
      other one showed initially steady improvement on high-frequency oscillatory
      ventilation for 20 hours, but ultimately died of unresolved cytomegalovirus
      pneumonitis and intractable pulmonary hemorrhage. There were 2 episodes of
      pneumothorax developing during high-frequency oscillatory ventilation. After
      decreasing mean airway pressure and amplitude, the airleak resolved with chest
      tube insertion. We conclude that high-frequency oscillatory ventilation with high
      lung-volume strategy may be an effective rescue therapy to relieve profound
      hypoxemia in infants and children with adult respiratory distress syndrome.

PMID- 9151468
TI  - Early echo-guided percutaneous aspiration of peripheral lung abscesses in
      children: report of two cases.
AB  - A 9 year-old boy and a 7 year-old girl suffered from fever and chest pains before
      they were brought to Chang Gung Children's Hospital. Chest radiographs and
      computed tomography scans showed lung abscesses with pleural attachment, and
      using echo-guidance, percutaneous aspirations were done which confirmed the
      growth of Fusobacterium sp, and Veillonella parvula respectively, both of which
      are susceptible to penicillin G. The fever and chest pains subsided within 24
      hours after the procedure. We suggest using early percutaneous aspiration of
      peripheral located lung abscesses soon after admission, rather than after a 10-14
      day trial of antibiotic therapy: it can be a safe and cost-effective procedure to
      shorten the duration of the parenteral antibiotic treatment and hospitalization.

PMID- 9151469
TI  - Ultrasonic demonstration of ectopic urethral ureter in duplex kidney: report of
      two cases.
AB  - Two cases of duplex kidney with ectopic urethral ureter are reported. Using
      abdominal ultrasound, the poorly functioning upper pole pelvis of the involved
      kidney was found to be sonolucent which may have been misinterpreted for a simple
      renal cyst. The corresponding ureter was dilated and drained into the proximal
      urethra. Ultrasound is an ideal imaging modality in the assessment of children
      with a duplicated renal system and may provide detailed information about this
      structural anomaly, such as the exact insertion of the ectopic ureter.

PMID- 9151471
TI  - Hydrops fetalis due to placental chorioangioma: report of one case.
AB  - Chorioangioma is the most common tumor of the placenta. However, a large one
      complicated with hydrops fetalis is rare. We report a patient who had hydrops
      fetalis associated with placental chorioangioma. The clinical manifestations
      included generalized edema, coagulopathy, thrombocytopenia, anemia,
      hypoproteinemia and hepatosplenomegaly. The hospital course was complicated with
      acute renal failure and repeated pneumonia. The patient died on the 54th day of
      life due to persistent lung atelectasis and hypovolemic shock. The
      pathophysiology and management of the complications of hydrops fetalis with
      chorioangioma are discussed.

PMID- 9151470
TI  - Cat scratch disease in a child.
AB  - We report a case of a 9-year-old girl scratched on the right side of her neck by
      a kitten about one month prior to admission. She was well until three weeks later
      when she developed enlarged right neck masses, a pustula on the scratch site,
      right injected conjunctiva, headache, general malaise and fever, thus fulfilling
      the clinical criteria for CSD. Initially, she was treated by a practicing
      physician but the manifestations persisted for one week. After admission,
      leukocytosis and a mildly elevated erythrocyte sedimentary rate were noted. The
      serum IgG titer to Bartonella henselae was performed by means of indirect
      fluorescent antibody (IFA) test at the National Institute of Preventive Medicine.
      The serum titer of anti-B, henselae Ig G was 1:256 and greater (> or = 1:256).
      The positive serum titer(negative titer being < 1:64) to B, henselae, the
      organism thought to be responsible for CSD, also supports this diagnosis. She was
      treated with a 7-day course of intravenous gentamicin and the fever subsided
      within 24 hours. Following this, she improved clinically and was discharged one
      week later. One month after discharge, she remained well with no palpable neck
      masses.

PMID- 9151472
TI  - Pseudomonas aeruginosa endophthalmitis in prematurity: report of two cases.
AB  - Invasive bacterial eye infections in the neonate range from perforating keratitis
      to endophthalmitis. Endophthalmitis secondary to Pseudomonas aeruginosa has
      gained clinical and therapeutic importance since mortality rates are high and
      prognosis concerning preservation of vision is poor, especially in premature
      infants. We presented two cases with meningitis, septicemia and P. aeruginosa
      endophthalmitis. If premature infants develop a sepsis-like picture with cloudy
      cornea and purulent conjunctivitis, we have to consider the possibility of
      endophthalmitis and do a full ophthalmologic evaluation. Treatment should be
      started early and consists of systemic antibiotic therapy, as in septicemia. As
      P. aeruginosa spreads easily, prompt isolation and strict handwashing are
      indicated.

PMID- 9151473
TI  - Pharmacokinetics and tissue residues of netilmicin and vancomycin in chickens.
AB  - Following a single intravenous injection of 10 mg netilmicin or 30 mg
      vancomycin/kg b.w. to normal chickens, the tested drugs obeyed a two or three
      compartments open model, with half-lives of distribution of 0.30 and 0.20 hours,
      respectively. The elimination half-lives following intravenous injection were
      0.41 and 4.85 hours, respectively. Following a single intramuscular injection of
      10 mg netilmicin or 30 mg vancomycin/kg b.w. to normal chickens, the serum drug
      concentrations peaked 2 hours post-injection with half-lives of absorption equal
      to 0.63 and 0.56 hours, respectively. The mean systemic bioavailability of
      netilmicin and vancomycin following a single intramuscular administration in
      normal chickens was 27.29 and 43.61%, respectively. These values indicated a
      limited and moderate absorption for netilmicin and vancomycin from intramuscular
      site, respectively. During repeated intramuscular administrations of both
      antibiotics for five consecutive days in normal chickens, the serum drug
      concentrations peaked two hours post each dose. The drugs concentrations during
      multiple dosage regimens were significantly increased in 2nd, 3rd, 4th and 5th
      days in comparison to the 1st day. Netilmicin and vancomycin persisted in liver
      and kidney for 96 and 120 hours, respectively, after the last intramuscular
      administration. The withdrawal time of netilmicin and vancomycin could be
      considered as five and six days, respectively. The in-vitro protein binding
      percents of netilmicin and vancomycin were 7.45 and 5.81%, respectively.

PMID- 9151474
TI  - Distribution of Aujeszky's disease virus in experimentally infected mink (Mustela
      vison).
AB  - Eight Mink (Mustela vison) were inoculated orally with Aujeszky's disease virus
      (ADV). Three mink were killed at the onset of clinical signs and the other mink
      died spontaneously after inoculation. The incubation period ranged from 72 to 96
      hours and was followed by a short illness characterised by increasing salivation,
      vomiting and retching, depression and coma. Microscopically, lesions were
      confined to the brain stem and consisted of a discrete non-suppurative
      encephalitis. Viral antigen was detected by an immunoperoxidase technique
      predominantly in association with specific lesions, although sometimes it was
      found within non-altered areas in the brain stem. Virus isolation confirmed the
      presence of ADV in the central nervous system. Fibrinoid degeneration of vessel
      walls was present in pharynx, larynx and myocardium in association with
      haemorrhages. Microthrombi were observed in heart and brain.

PMID- 9151475
TI  - Association of Pasteurella haemolytica, Pasteurella multocida and Haemophilus
      somnus with pneumonia in calves.
AB  - Pathological and bacteriological observations were made on 100 (0.98%) pneumonic
      lungs of 10140 slaughtered beef calves during March 1995-June 1996 period. Gross
      lesions were mainly lobular and occasionally lobar pattern and, were frequently
      observed in the pars cranialis of lobus cranialis dexter. In histological
      examination, proliferative-exudative pneumonia was observed in 79 cases, and
      proliferative pneumonia alone in 21 cases. In bacteriological examination,
      Pasteurella haemolytica. Pasteurella multocida and Haemophilus somnus were
      isolated from 42.8 and 10 of pneumonic lungs respectively. In 7 cases, P.
      haemolytica and H. somnus were isolated from the same sample P. haemolytica and
      P. multocida were also found in the same sample in 2 cases. There was a close
      relation among these organisms and exudative inflammation (P < 0.01).

PMID- 9151476
TI  - A new method for myocardial activation imaging.
AB  - Noninvasive images of the myocardial activation sequence are acquired, based on a
      new formulation of the inverse problem of electrocardiography in terms of the
      critical points of the ventricular surface activation map. It is shown that the
      method is stable with respect to substantial amounts of correlated noise common
      in the measurements and modeling of electrocardiography and that problems
      associated with conventional regularization techniques can be circumvented.
      Examples of application of the method to measured human data are presented. This
      first invasive validation of results compares well to previously published
      results obtained by using a standard approach. The method can provide additional
      constraints on, and thus improve, traditional methods aimed at solving the
      inverse problem of electrocardiography.

PMID- 9151477
TI  - Generalized eigensystem techniques for the inverse problem of electrocardiography
      applied to a realistic heart-torso geometry.
AB  - We have previously proposed two novel solutions to the inverse problem of
      electrocardiography, the generalized eigensystem technique (GES) and the modified
      generalized eigensystem technique (tGES), and have compared these techniques with
      other numerical techniques using both homogeneous and inhomogeneous eccentric
      spheres model problems. In those studies we found our generalized eigensystem
      approaches generally gave superior performance over both truncated singular value
      decomposition (SVD) and zero-order Tikhonov regularization (TIK). In this paper
      we extend the comparison to the case of a realistic heart-torso geometry. With
      this model, the GES and tGES approaches again provide smaller relative errors
      between the true potentials and the numerically derived potentials than the other
      methods studied. In addition, the isopotential maps recovered using GES and tGES
      appear to be more accurate than the maps recovered using either SVD and TIK.

PMID- 9151478
TI  - Investigation of a Lorentz force biomagnetometer.
AB  - This work evaluates an approach to the noninvasive measurement of small ionic
      current flows by a technique of Lorentz force magnetometry. An instrument was
      constructed that is basically a very sensitive force-balance that can measure
      Lorentz forces experienced by ionic currents flowing in small objects when
      exposed to strong oscillating magnetic fields. For objects that can fit on a
      microscope slide, the system is sensitive to ion current dipole moments as low as
      180 pA-m. Images were made of ionic currents flowing in thin profiles by a
      process of scanning a localized magnetic field over the object, measuring
      generated Lorentz forces, and using a computer to reconstruct images. It can be
      shown that this method of Lorentz magnetometry has an immunity to ambient
      magnetic noise and has system characteristics that might suggest its possible use
      in biomagnetometry of small thin specimens.

PMID- 9151479
TI  - Development and application of ultrasonic surgical instruments.
AB  - In this paper, a new approach for designing ultrasonic surgical instruments (USI)
      is presented. These medical instruments convert an ultrasonic signal into a
      mechanical vibration by utilizing a magnetostrictive method and have been found
      to be very useful for various medical procedures. The implemented system consists
      of an ultrasonic generator, a transducer, and waveguide instruments. The
      generator produces a high-current ultrasonic signal. The transducer converts this
      signal into a mechanical vibration. By use of the waveguide instrument, the
      vibration can be propagated and amplified. This new type of USI possesses a
      comprehensive ability to stop bleeding, cut bone tissues, regulate frequency
      automatically, control temperature, etc. The results from animal experiments and
      from human clinical operations show that the developed USI has the advantages in
      various aspects over the conventional equipment.

PMID- 9151480
TI  - An imaging colorimeter for noncontact tissue color mapping.
AB  - There has been a considerable effort in several medical fields, for objective
      color analysis and characterization of biological tissues. Conventional
      colorimeters have proved inadequate for this purpose, since they do not provide
      spatial color information and because the measuring procedure randomly affects
      the color of the tissue. In this paper an imaging colorimeter is presented, where
      the nonimaging optical photodetector of colorimeters is replaced with the charge
      coupled device (CCD) sensor of a color video camera, enabling the independent
      capturing of the color information for any spatial point within its field-of
      view. Combining imaging and colorimetry methods, the acquired image is calibrated
      and corrected, under several ambient light conditions, providing noncontact
      reproducible color measurements and mapping, free of the errors and the
      limitations present in conventional colorimeters. This system was used for
      monitoring of blood supply changes of psoriatic plaques, that have undergone
      Psoralens and ultraviolet-A radiation (PUVA) therapy, where reproducible and
      reliable measurements were demonstrated. These features highlight the potential
      of the imaging colorimeters as clinical and research tools for the
      standardization of clinical diagnosis and for the objective evaluation of
      treatment effectiveness.

PMID- 9151481
TI  - Determination of glucose concentrations in an aqueous matrix from NIR spectra
      using optimal time-domain filtering and partial least-squares regression.
AB  - We have investigated the use of a time-domain optimal filtering method to
      simultaneously minimize both the baseline variation and high-frequency noise in
      near-infrared (NIR) spectrophotometric absorption data of glucose dissolved in a
      simple aqueous (deionized water) matrix. By coupling a third-order (six-pole)
      digital Butterworth bandpass filter with partial least-squares (PLS) regression
      modeling, glucose concentrations were determined for a set of test data with a
      standard error of prediction (SEP) of 10.53 mg/dl (mean percent error: 4.24%)
      using seven PLS factors. Compared to the unfiltered test data for six PLS factors
      and a SEP = 17.00 (mean percent error: 7.38%) this results shows more than a 38%
      decrease in the error. The glucose concentrations ranged from 51 mg/dl to 493
      mg/dl, and the NIR spectral region between 2088 nm and 2354 nm (4789 cm-1 and
      4248 cm-1) was used to develop the optimal PLS model. The optimal PLS model was
      determined from a sequence of three-dimensional performance response maps for
      different numbers of PLS factors (2-10). A total of 99 NIR spectra were generated
      for glucose dissolved in deionized water using a NIRsystems 5000 dispersive
      spectrophotometer. Nine of these spectra were generated for only water, which
      were averaged and subtracted from the remaining 90 spectra to generate the
      training and test data sets, thereby, removing the intrinsic high background
      absorption due to the water. The training set consisted of 57 spectra and
      associated glucose concentration target values, and the test set was comprised of
      the remaining 33 spectra and target values. Performance results were compared for
      three different digital Butterworth bandpass filters (four-poles, six-poles, and
      eight-poles), and a digital Gaussian filter design approach (i.e., Fourier
      filtering).

PMID- 9151482
TI  - Suboptimal dual adaptive control for blood pressure management.
AB  - This paper presents a new approach for adaptive control of blood pressure using
      vasoactive drugs. The idea is to use an adaptive controller that incorporates the
      concept of duality in the sense of Feldbaum and to consider the cost functional M
      steps ahead in time. The dual property means that the control signal is chosen in
      such a way that estimation of the model parameters and regulation of the output
      signals are optimally balanced. Extensive computer simulations for different
      values of M shows that the sample mean of the achieved cost tends asymptotically
      to a limiting value while the variance is reduced. The proposed subotimal
      adaptive controller has also an improved transient response when compared to a
      certainty equivalent controller.

PMID- 9151483
TI  - Identification of intrinsic and reflex contributions to human ankle stiffness
      dynamics.
AB  - We have examined dynamic stiffness at the human ankle using position
      perturbations which were designed to provide a wide-bandwidth input with low
      average velocity. A parallel-cascade, nonlinear system identification technique
      was used to separate overall stiffness into intrinsic and reflex components.
      Intrinsic stiffness was described by a linear, second-order system similar to
      that demonstrated previously. Reflex stiffness dynamics were more complex,
      comprising a delay, a unidirectional rate-sensitive element and then lowpass
      dynamics. Reflex mechanisms were found to be most important at frequencies of 5
      10 Hz. The gain and dynamics of reflex stiffness varied strongly with the
      parameters of the perturbation, the gain decreasing as the mean velocity of the
      perturbation increased. Under some conditions, torques generated by reflex
      mechanisms were of the same magnitude as those from intrinsic mechanisms. It is
      concluded that reflex stiffness can be large enough to be important functionally,
      but that its effects will depend strongly upon the particular conditions.

PMID- 9151484
TI  - Design of a recognition system to predict movement during anesthesia.
AB  - The need for a reliable method of predicting movement during anesthesia has
      existed since the introduction of anesthesia. This paper proposes a recognition
      system, based on the autoregressive (AR) modeling and neural network analysis of
      the electroencephalograph (EEG) signals, to predict movement following surgical
      stimulation. The input to the neural network will be the AR parameters, the
      hemodynamic parameters blood pressure (BP) and heart rate (HR), and the
      anesthetic concentration in terms of the minimum alveolar concentration (MAC).
      The output will be the prediction of movement. Design of the system and results
      from the preliminary tests on dogs are presented in this paper. The experiments
      were carried out on 13 dogs at different levels of halothane. Movement prediction
      was tested by monitoring the response to tail clamping, which is considered to be
      a supramaximal stimulus in dogs. The EEG data obtained prior to tail clamping was
      processed using a tenth-order AR model and the parameters obtained were used as
      input to a three-layer perceptron feedforward neural network. Using only AR
      parameters the network was able to correctly classify subsequent movement in 85%
      of the cases as compared to 65% when only hemodynamic parameters were used as the
      input to the network. When both the measures were combined, the recognition rate
      rose to greater than 92%. When the anesthetic concentration was added as an input
      the network could be considerably simplified without sacrificing classification
      accuracy. This recognition system shows the feasibility of using the EEG signals
      for movement during anesthesia.

PMID- 9151485
TI  - Noise reduction for NMR FID signals via Gabor expansion.
AB  - The parameters in a nuclear magnetic resonance (NMR) free induction decay (FID)
      signal contain information that is useful in biological and biomedical
      applications and research. A real time-sampled FID signal is well modeled as a
      finite mixture of modulated exponential sequences plus noise. We propose to use
      the generalized Gabor expansion for noise reduction, where the generalized Gabor
      expansion represents a signal in terms of a collection of time-shifted and
      frequency-modulated versions of a single sequence (prototype sequence). For FID
      signal-fitting, we choose the exponential sequence as the prototype function.
      Using the generalized Gabor expansion and exponential prototype sequences for FID
      model-fitting, an NMR FID signal can be well represented by the Gabor
      coefficients distributed in the joint time-frequency domain (JTFD). The Gabor
      coefficients reflect the weights of modulated exponential sequences in a signal.
      One of the important features is that the nonzero Gabor coefficients of a
      modulated exponential sequence will span a very small area in the JTFD, whereas
      the Gabor coefficients of the noise will not. If the exponent constant of the
      prototype sequence in the generalized Gabor expansion matches that of a modulated
      exponential sequence in the signal, then only one of the Gabor coefficients is
      nonzero in the JTFD. This is a very important property since it can be exploited
      to separate a signal from noise and to estimate modulated exponential sequence
      parameters.

PMID- 9151486
TI  - Triatoma virus pathogenicity in laboratory colonies of Triatoma infestans
      (Hemiptera:Reduviidae).
AB  - In a survey of wild populations of Triatoma infestans (Klug) in Argentina, 10%
      were infected with Triatoma virus (TrV). The virus also was detected in a
      laboratory colony 18 mo after being established, with infection rates up to 100%.
      Mortality rate was 97.6% in nymphs and the molting process was inhibited, thereby
      increasing development time. Because the virus was detected in colony nymphs. TrV
      may be transmitted vertically. However, the higher infection rate in the colony
      compared with natural populations also indicates other route(s) of transmission.

PMID- 9151487
TI  - Abundance, parity, and Japanese encephalitis virus infection of mosquitoes
      (Diptera:Culicidae) in Sepang District, Malaysia.
AB  - A 2-yr study of Japanese encephalitis (JE) virus in Sepang District, Selangor,
      Malaysia, was carried out to identify the mosquito vectors and to determine their
      seasonal abundance, parity, and infection rates. In total, 81,889 mosquitoes
      belonging to 9 genera and > 50 species were identified from CDC trap collections
      augmented with dry ice during 1992 and 1993. Culex tritaeniorhynchus Giles and
      Culex gelidus Giles were the most abundant species, and both increased in numbers
      with increases in rainfall. Overall, 45 JE virus isolations were made from 7
      species-Cx. tritaeniorhynchus (24), Cx. gelidus (12), Culex fuscocephala Theobald
      (2), Aedes butleri Theobald (4), Culex quinquefasciatus Say (1), Aedes
      lineatopennis Ludlow (1), and Aedes (Cancraedes) sp. (1). Based on elevated
      abundance and JE infection rates, Cx. tritaeniorhynchus appears to be the most
      important vector of JE virus in Sepang.

PMID- 9151489
TI  - Effects of rice culture practices on the abundance of Culex mosquitoes
      (Diptera:Culicidae) in northern Thailand.
AB  - In 1991-1993, the density (numbers per 10 dips) and abundance (density x flooded
      area) of mosquitoes were studied in 3 areas of northern Thailand with different
      environmental conditions. Culex tritaeniorhynchus Giles, Cx. vishnui Theobald,
      and Cx. gelidus Theobald were predominant among the 8 Culex species collected.
      Abundance of these 3 species varied significantly among the 3 areas. Type of
      habitat classified according to agricultural practices in rainy and dry season
      significantly influenced larval abundance of Cx. tritaeniorhynchus and Cx.
      vishnui. Seasonal variation in larval abundance was significant only in Cx.
      vishnui. The response of the 3 vector mosquitoes to environmental heterogeneity
      is discussed.

PMID- 9151488
TI  - Status of malaria vectors in Italy.
AB  - About 30 yr after malaria eradication, surveys to assess the presence and
      abundance of anopheline vectors were carried out in central and southern Italy
      and in the islands of Sardinia and Sicily from 1992 to 1994. Anopheles
      labranchiae Falleroni was present in scattered foci in all regions, except for
      Tuscany, where it breeds almost exclusively in rice fields (Grosseto Province).
      Most common breeding sites were rivers and streams, followed by ponds and ground
      pools. The highest adult density was found in Tuscany near rice fields and along
      the west coast of Calabria. Anophelines in Grosseto were abundant at human bait,
      with peaks of > 200 landings per human per night and vectorial capacity between
      7.3 and 26 for Plasmodium falciparum and between 8.3 and 32.5 for Plasmodium
      vivax. Anopheles sacharovi Favre, a former malaria vector in Puglia and Sardinia,
      was not found in these regions. The other vector in southern Italy, Anopheles
      superpictus Grassi, was found at low densities on the western and eastern coasts
      of Calabria. All anopheline populations were fully susceptible to deltamethrin,
      malathion, and DDT but showed reduced susceptibility to permethrin and propoxur.
      These data are discussed in the light of a possible reintroduction of malaria
      into Italy.

PMID- 9151490
TI  - Field morphological variation and laboratory hybridization of Culicoides
      variipennis sonorensis and C. v. occidentalis (Diptera:Ceratopogonidae) in
      southern California.
AB  - Two field populations of Culicoides variipennis (Coquillett) from southern
      California, C. v. occidentalis Wirth & Jones from the Salton Sea and C. v.
      sonorensis Wirth & Jones from a dairy wastewater pond in the Chino Basin, were
      sampled monthly from February to July (6-7 mo). Morphometric analyses of slide
      mounted adults reared from field-collected larvae and pupae indicated that
      females of the 2 forms were indistinguishable. Two of the standard characters,
      wing length and mandibular teeth, were correlated with seasonal temperature
      changes. Males of C. v. sonorensis were distinguishable by the presence of
      spicules on the aedeagus, which were entirely lacking in C. v. occidentalis. Two
      populations of C. v. occidentalis (Salton Sea and Bolsa Chica Marsh) and a
      laboratory strain of C. v. sonorensis hybridized successfully in the laboratory
      and were maintained for 6 generations. Differential hybrid viability (F1) was
      observed in reciprocal crosses. Males of C. v. occidentalis mated with females of
      C. v. sonorensis resulted in a lower egg hatch (7.4%) than did the reciprocal
      cross (75.6%). Hybrid males displayed spicules on the aedeagus (a character of C.
      v. sonorensis), but the number of spicules was sometimes reduced compared with
      parental C. v. sonorensis (AA strain). Spicules in a field population of C. v.
      sonorensis were similar in number to the laboratory C. v. sonorensis-C. v.
      occidentalis hybrids. Based on successful hybridization, the 2 forms should be
      considered closely related. The 2 forms are separated ecologically by the nature
      and distribution of their larval habitats.

PMID- 9151491
TI  - Indoor resting by outdoor biting females of Anopheles gambiae complex
      (Diptera:Culicidae) in the Sahel of northern Senegal.
AB  - Three villages in the Senegal River basin were selected to study the biting and
      resting behavior of Anopheles gambiae s.l. in relation to human habits,
      rainfalls, and rice culture irrigation. All inhabitants sleep outside throughout
      the year, mainly under poor quality bednets. Mosquitoes were collected host
      seeking during the night on human bait outside and resting during the day inside
      and outside in pit shelters. An. gambiae s.s. and An. arabiensis fed mainly
      outside, the only place where hosts are available; fed and gravid females resting
      indoors fed outside. The proportions of An. gambiae s.s. and An. arabiensis in
      outdoor biting catches and in indoor spray catches were not significantly
      different, but they differed from year to year with the latter sampling method,
      An. gambiae s.s. predominated in 1990, a more wet and humid year, whereas An.
      arabiensis was more common in 1991, which was an arid year. Both species are
      highly endophilic in this arid area where outdoor-resting places are limited.

PMID- 9151492
TI  - Anopheline (Diptera:Culicidae) breeding in a traditional tank-based village
      ecosystem in north central Sri Lanka.
AB  - A 13-mo survey of immature anopheline mosquitoes breeding in surface water
      habitats was done at Mahameegaswewa village within the Huruluwewa watershed in
      north central Sri Lanka as part of a multidisciplinary study on malaria
      epidemiology. The watershed is representative of the ancient small tank-based
      irrigation network that still forms an important component of the rice production
      system in the low elevation dry zone. In total, 3,818 immatures representing 12
      species were obtained from 2,940 samples taken from 5 larval habitats within the
      village ecosystem. Anopheles varuna Iyengar and An. culicifacies Giles were the
      most abundant species collected. Peak abundance in both species occurred in
      August-October. Anopheles barbirostris Van der Wulp and An. peditaeniatus
      Leicester also were abundant, but neither these nor the other anophelines
      attained comparable abundance to An. varuna and An. culicifacies. A clear
      progression in breeding habitat use from stream bed to tank bed and drainage area
      pools was seen in An. culicifacies during the premonsoon period. Environmental
      management measures to reduce or modify these habitats could potentially decrease
      malaria. transmission.

PMID- 9151493
TI  - Enema infusion technique inappropriate for evaluating viral competence of ticks.
AB  - To determine whether anal infusion of virus simulates the natural route of
      infection rather than intracoelomic injection, we compared the course of
      Venezuelan equine encephalitis (VEE) virus infection in Amblyomma cajennense (F.)
      ticks that had been exposed to virus by enema infusion with that in ticks fed on
      a viremic host or exposed by intracoelomic inoculation. Although virus was
      detected in virtually all ticks 14 d after exposure, orally exposed ticks
      contained significantly less virus (10(1.9) plaque-forming units [PFU] per tick)
      than did ticks infected by enema (10(4.1) PFU per tick) or intracoelomically
      (10(4.2) PFU per tick). At 42 d after virus exposure, only 1% of 512 orally
      exposed ticks contained virus, but most enema (77%, n = 43) or intracoelomically
      (79%, n = 29) exposed ticks were infected. Replication of VEE virus in A.
      cajennense ticks exposed to virus by enema infusion, therefore, appeared more
      similar to that of ticks inoculated intracoelomically than to those exposed
      orally. Thus, because enema infusion may bypass potential midgut infection and
      escape barriers, this procedure may not be appropriate for determining vector
      competence in ixodid ticks.

PMID- 9151494
TI  - Density-dependent seasonal dynamics of blacklegged tick (Acari:Ixodidae) nymphs.
AB  - The midsummer seasonal decline in abundance of unfed Ixodes scapularis Say nymphs
      on experimental plots in New Jersey was density-dependent. Nymph density was
      manipulated on 9 plots (10 by 10 m each) in Morristown. National Historical Park,
      NJ, in early June 1994. Subsequent rates of decline were directly proportional to
      initial density (linear regression, R2 = 0.83). A 6-fold manipulation of density
      caused more than a 10-fold increase in per-capita disappearance rate. Absence of
      density-dependent mortality in simultaneous field cage experiments implicated
      dispersal at rates higher than reported previously, positive-density-dependent
      host finding success, or predation, possibly in the form of host grooming. Each
      of these possibilities has important implications for the role of unfed nymphs in
      the regulation of I. scapularis populations.

PMID- 9151495
TI  - Evaluation of German cockroach (Orthoptera:Blattellidae) allergen and seasonal
      variation in low-income housing.
AB  - Six apartments in a low-income housing project were evaluated for German
      cockroach. Blattella germanica (L.), infestation and concentration of an allergen
      derived from these cockroaches (Bla g II). Kitchen and living room samples were
      collected monthly for 1 yr. In addition, airborne sampling was carried out in 5
      kitchens. The kitchen had the highest allergen concentration in 65% of visits and
      the highest number of cockroaches trapped in 69% of visits. In the kitchen, the
      highest cockroach levels were seen in June, whereas the values for Bla g II
      peaked in August. In keeping with this, the closest correlation was between Bla g
      II (microgram/g dust) and the number of cockroaches found 2 mo earlier. Airborne
      samples were assayed for 2 separate allergens. Bla g II and Bla g I. No allergen
      was detectable in the absence of disturbance. By contrast, during disturbance
      with a vacuum cleaner both Bla g II and Bla g I were detectable in the air of
      each apartment. Results suggest that immunochemical assay of a major allergen in
      dust samples from the kitchen floor may be used to monitor exposure to German
      cockroaches, also that cockroach levels may be used as an indicator or predictor
      of allergen in dust.

PMID- 9151496
TI  - Multivariate analysis to discriminate species of phlebotomine sand flies
      (Diptera:Psychodidae): Lutzomyia townsendi, L. spinicrassa, and L. youngi.
AB  - Multivariate discriminant analysis was employed to discriminate on a
      morphological basis females of 3 closely related sand fly species, Lutzomyia
      townsendi (Ortiz), L. spinicrassa Morales, Osorno-Mesa, Osorno & Hoyos, and L.
      youngi Feliciangeli & Murillo. Principal component and canonical discriminant
      analysis compared a set of 31 morphological characters measured from known
      specimens to detect differences among the 3 species. A subset of 6 characters
      separated the 3 species with a high level of confidence. A simple method is
      presented to identify an unknown specimen as L. townsendi, L. spinicrassa, or L.
      youngi using these 6 morphological characters.

PMID- 9151497
TI  - Demodex sinocricetuli: new species of hair follicle mite (Acari:Demodecidae) from
      the Chinese form of the striped hamster, Cricetulus barabensis
      (Rodentia:Muridae).
AB  - Demodex sinocricetuli sp. nov. is described in all its life stages from the
      Chinese form of the striped hamster, Cricetulus barabensis. A large sample size
      of > 11,500 mites (96% adults and only 4% ova and immatures) was surveyed. The
      cause of the apparent reproductive stasis is not known. Limited data sets from
      other demodecid species reveal populations that are 42-82% adult.

PMID- 9151499
TI  - Arthropod succession on exposed carrion in three contrasting tropical habitats on
      Hawaii Island, Hawaii.
AB  - Decomposition studies were conducted using domestic pig carcasses to determine
      arthropod succession patterns on exposed carrion for the island of Hawaii. The
      carcasses were placed in upland forest and woodland (1,877 m), rainforest (1,169
      m) and midelevation woodlands (646 m) habitats. Marked differences in species
      composition, rates of biomass removal, and succession patterns were observed
      between these 3 sites. These results also differed from patterns observed during
      previous decomposition studies conducted on the island of Oahu.

PMID- 9151498
TI  - Resistance to Bacillus sphaericus involves different mechanisms in Culex pipiens
      (Diptera:Culicidae) larvae.
AB  - Field Culex pipiens pipiens (L.) mosquitoes that were collected after a control
      failure with Spherimos in southern France developed high resistance (> 10,000
      fold) to Bacillus sphaericus crystal toxin after < 8 generations of laboratory
      selection. We show that this resistance is encoded by a single major recessive
      gene on linkage group I at 22.1 recombination units from the sex locus, and that
      it is not associated with any loss of binding affinity between brush border
      membrane fractions and the B. sphaericus radiolabeled toxin. Thus, in Southern
      France, resistance differs from the high B. sphaericus resistance developed after
      laboratory selection of Californian C. p. quinquefasciatus. This demonstrates
      that at least 2 different mechanisms may confer high levels of resistance to B.
      sphaericus crystal toxin in mosquitoes of the C. pipiens complex. These results
      have important implications for mosquito control strategies.

PMID- 9151500
TI  - Susceptibility of immature Ixodes scapularis (Acari:Ixodidae) to plant-derived
      acaricides.
AB  - Plant-derived acaricides, extracted from various botanical species, and
      commercially available phytochemicals were evaluated for biological activity
      against immature Ixodes scapularis (Say) using the disposable pipet method. In
      addition, residual activity of the plant extracts was determined. Of the 13 plant
      extracts tested, 9 exhibited biological activity with Alaska yellow cedar,
      Chamaecyparis nootkatensis (D. Don) Spach., being the most effective against the
      nymphal ticks (LC50 = 0.151% wt:vol) and eastern red cedar, Juniperus virginiana
      L., showing the greatest activity against larval ticks (LC50 = .001% wt:vol). The
      commercially available products were significantly less active than the plant
      extracts we prepared, but some commercial compounds did exhibit limited activity.
      Only the Alaska yellow cedar exhibited any residual activity that lasted 21 d
      after treatment.

PMID- 9151501
TI  - Vector competence of mosquitoes (Diptera:Culicidae) from Massachusetts for a
      sympatric isolate of eastern equine encephalomyelitis virus.
AB  - We tested susceptibility to per os infection and potential salivary transmission
      for eastern equine encephalomyelitis (EEE) virus in Aedes canadensis (Theobald),
      Aedes vexans (Meigen), Anopheles quadrimaculatus (Say), Anopheles punctipennis
      (Say), Coquillettidia perturbans (Walker), and Culex salinarius (Coquillett).
      Culiseta melanura (Coquillett), the documented enzootic vector of EEE virus, was
      our control. Based on these estimates of laboratory vector competence and other
      behavioral and ecological components of vectorial capacity, we ranked these 6
      species from the most to least probable epidemic vectors: Cx. salinarius, An.
      quadrimaculatus, Ae. canadensis, Cq. perturbans, Ae. vexans, and An.
      punctipennis.

PMID- 9151502
TI  - Effects of temperature on Chrysomya rufifacies (Diptera:Calliphoridae)
      development.
AB  - Growth curves were studied for the egg, larva, and pupa of Chrysomya rufifacies
      (Macquart) under mean cyclic temperatures of 15.6, 21.1, 26.7, and 35.0 degrees C
      and a constant temperature of 25.0 degrees C. Development from egg to adult under
      all regimes ranged from 190 to 598 h. A constant temperature of 25 degrees C
      produced a range of pupation times from 134 to 162 h, with adult emergence
      ranging from 237 to 289 h. The maximal preferential temperature of 35.1 degrees C
      was determined for maggots using a gradient system. Highly predictable
      developmental time, minimal larval length variation, and low cohort variation
      emphasize the utility of this species in entomological-based postmortem interval
      determinations. Therefore, C. rufifacies should be of primary forensic importance
      when recovered alone or in conjunction with other species of Calliphoridae.

PMID- 9151503
TI  - Parasites of mammals on the Sevilleta National Wildlife Refuge, Socorro, New
      Mexico: Cuterebra austeni and C. neomexicana (Diptera:Oestridae) from Neotoma and
      Peromyscus (Rodentia:Muridae), 1991-1994.
AB  - In total, 6,486 rodents representing 3 families (Muridae, Heteromyidae, and
      Sciuridae) and 24 species were trapped May through August of 1991 through 1994.
      Of these, only the white-throated woodrat. Neotoma albigula Hartley; pinon mouse,
      Peromyscus truei Shufeldt; and white-footed mouse, P. leucopus Rafinesque, were
      infested with Cuterebra Clark larvae. Of the 594 N. albigula that were captured
      103 (17.3%) were infested with 139 Cuterebra larvae with all infestations
      occurring in the throat region. N. albigula infestations were observed in 4 of 5
      habitats sampled. The highest prevalence of infestation occurred during May-June
      (27.2%) versus July-August (9.1%) and in males (25.2%) versus females (18.3%).
      Prevalence of infestation was not significantly different between animals from
      the mark-release webs versus removal webs or adults versus juveniles. Also, there
      was no correlation between relative density of N. albigula and prevalence of
      infestation. Fifteen adults were reared from puparia and identified as C. austeni
      Sabrosky. Of 716 P. truei captured, 22 (3.1%) were infested with a total of 25
      Cuterebra larvae with all infestations occurring in the scapular region. Although
      P. truei were captured in all 5 habitats, they were only infested in the pinon
      juniper habitat: the highest prevalence of infestation occurred during July
      August (10.9%) versus May-June (3.3%). Prevalence of infestation was not
      significantly different between animals from mark-release webs versus removal
      webs, males versus females, or adults versus juveniles. As in the N. albigula,
      there was no correlation between relative density of P. truei and prevalence of
      infestation. The adult reared from a puparium was identified as C. neomexicana
      Sabrosky. Of the 310 P. leucopus captured, only 3 (1%) were infested with
      Cuterebra larvae.

PMID- 9151504
TI  - A new species of Leptotrombidium (Acari:Trombiculidae) collected in active rice
      fields in northern Thailand.
AB  - Leptotrombidium (Leptotrombidium) chiangraiensis Tanskul & Linthicum is described
      and illustrated as new from specimens collected from the rodents Rattus rattus
      (L., 1758), Rattus argentiventer (Robinson & Kloss, 1916), Rattus losea (Swinhoe,
      1870), and Bandicota indica (Bechstein, 1800) in Chiangrai Province northern
      Thailand. The new species was collected in active rice fields and adjacent fruit
      plantation areas. The etiological agent of scrub typhus, Orientia (formerly
      Rickettsia) tsutsugamushi (Hayashi), has been isolated from patients who live and
      work in the same habitat where L. chiangraiensis is the predominant
      Leptotrombidium species.

PMID- 9151505
TI  - Some factors affecting infestation of white-tailed deer by blacklegged ticks and
      winter ticks (Acari:Ixodidae) in southeastern Missouri.
AB  - A total of 5,669 ticks of 4 species was collected from 515 hunter killed, white
      tailed deer. Odocoileus virginianus (Zimmerman), in southeastern Missouri from
      1993 through 1995. The American dog tick, Dermacentor variabilis (Say) (4
      adults), the lone star tick,  Amblyomma americanum (L.) (57 adults, 2 nymphs),
      the blacklegged tick, Ixodes scapularis (Say) (3,120 adults), and the winter
      tick, Dermacentor albipictus (Packard) (2.059 adults, 436 nymphs, 1 larva) were
      collected. Patterns of adult D. albipictus and I. scapularies infesting deer were
      analyzed with respect to upland versus lowland habitat, county, and host sex.
      Prevalence and intensity of infestation by D. albipictus were higher on bucks
      than does, and a higher infestation prevalence was recorded for this tick on deer
      from upland than from lowland habitats. Mean intensities for D. albipictus were
      not significantly different between counties. Prevalence and mean intensity of
      infestation for I. scapularis were significantly higher on deer from uplands than
      lowlands and on bucks than does; mean intensities also differed between counties
      for this tick. Because adjacent populations, as well as the sex of the host, can
      differ in infestation rates, differences between local populations of I.
      scapularis should be recognized to optimize tick surveys and population models.

PMID- 9151506
TI  - Computer modeling: a new approach to the investigation of disease.

PMID- 9151507
TI  - Why Java can't print (yet).

PMID- 9151508
TI  - A computational model of the progression of Alzheimer's disease.
AB  - Computational modeling allows analysis of the role of network dynamics in the
      initiation and progression of neuropathology in Alzheimer's disease. The model
      focuses on a final common breakdown in function, termed runaway synaptic
      modification. This phenomenon could account for evidence that neuropathological
      markers associated with neuronal death in Alzheimer's disease first appear and
      attain their highest concentration in subregions of the hippocampal formation,
      and then successively spread into the temporal lobe cortex and the cortex of the
      frontal and parietal lobes. The model demonstrates how the spread of
      neuropathology from the hippocampus into neocortical structures could result from
      the mechanisms of consolidation. Initial sensitivity of the hippocampus and
      entorhinal cortex to the neuropathological process is proposed to result from an
      imbalance of variables regulating the influence of synaptic transmission on
      synaptic modification. Memory deficits are described as due to increased
      interference effects on recent memory caused by runaway synaptic modification,
      which ultimately leads to impairments of remote and semantic memory.

PMID- 9151509
TI  - Noise-driven neuroplasticity in self-organizing feature maps: a
      neurocomputational model of phantom limbs.
AB  - The term "phantom limb" denotes the sensation that an extremity is present
      although it has been lost. A number of clinical features and recent findings of
      cortical map plasticity after destruction of afferent pathways (deafferentation)
      suggest that phantom limbs are caused by large-scale cortical reorganization
      processes. However, in paraplegics, who also suffer from cortical
      deafferentation, phantom sensations rarely develop, and if they do, they are
      weak, lacking in detail, and delayed, occurring after months. This has been taken
      to suggest a non-cortical genesis of phantom limbs. This article proposes a
      biologically plausible minimal neural network model to solve this apparent
      puzzle. Deafferentation was simulated in trained self-organizing feature maps.
      Reorganization was found to be directed by input noise. According to the model,
      the production of input noise by the deafferented primary sensory neuron promotes
      cortical reorganization in amputees. No such noise is generated or conducted to
      the cortex in paraplegics.

PMID- 9151510
TI  - Neural network simulations, cortical connectivity, and schizophrenic psychosis.
AB  - Recent studies have suggested that reduced corticocortical connectivity is
      associated with schizophrenia. My colleagues and I have used neural network
      simulations to explore parallel, distributed processing systems with reduced
      connectivity. These systems often behaved in a "schizophrenic-like" manner.
      Excessively pruned attractor networks became functionally fragmented, suggesting
      "loose associations," and produced recurrent, intrusive representations
      suggestive of delusions. Pruning backpropagation simulations of speech perception
      networks produced spontaneous output, which provided a model of auditory
      hallucination or "voices." This model also suggested how dopamine-blocking drugs
      may reduce positive symptoms, and why negative symptoms arise in the wake of
      positive symptoms.

PMID- 9151511
TI  - Cause of death in COPD: still an open question?

PMID- 9151512
TI  - Pulmonary function in patients with systemic sclerosis.
AB  - The lungs are frequently affected in systemic sclerosis (SSc), a generalized
      connective tissue disorder. We evaluated the prevalence of respiratory functional
      abnormalities and their correlation with symptoms and radiograph features in a
      group of 34 patients who fulfilled the American Rheumatism Association criteria
      for the diagnosis of systemic sclerosis. Patients were submitted to a specific
      respiratory questionnaire and to lung function tests. Measurements were performed
      according to the European Coal and Steel Community (ECSC) recommendations and
      results expressed as a SD score, an accurate method that, taking into account the
      dispersion of the parameters in the reference population, allows precise
      definition of pathological subjects. Of the patients examined, 38% reported
      dyspnoea at rest or on exertion. No other respiratory symptoms were reported.
      Fifty percent had a normal chest radiograph. This study documents the high
      prevalence of respiratory functional abnormalities in patients with SSc. A
      restrictive pattern was found in 41% and an isolated diffusion impairment in 18%.
      No significant relationship was found between the isolated impairment of transfer
      factor of the lungs for carbon monoxide (TL,CO) and the mean duration of the
      scleroderma: thus, it does not seem to represent an early sign of severe
      restrictive disease. No bronchial or bronchiolar obstructive patterns were
      observed: it can be stated that small airways dysfunction is not a characteristic
      manifestation of SSc as considered previously. A significant association was
      found between the group of subjects with chest radiographic abnormalities and
      that with a restrictive pattern or isolated TL,CO alteration (p = 0.018). Chest
      radiographic abnormalities were also found in 29% and dyspnoea in 35% of the
      patients with normal respiratory function. The mean duration of scleroderma was
      not significantly different between the groups with and without abnormalities on
      chest radiography, between the groups with and without a restrictive pattern or
      isolated diffusion impairment, and between the groups of patients with and
      without dyspnoea. In conclusion, an accurate evaluation of respiratory function
      is recommended in the assessment of patients with systemic sclerosis, since the
      functional involvement of the lung cannot be predicted on the basis of the chest
      radiograph and the respiratory symptoms.

PMID- 9151513
TI  - Correction of hypoxia and hypercapnia in COPD patients: effects on
      cerebrovascular flow.
AB  - To assess the responsiveness of cerebral blood flow to arterial carbon dioxide
      tension (Pa,CO2), arterial oxygen tension (Pa,O2), and pH modifications, in
      chronic hypercapnia, we measured middle cerebral blood flow velocity (CBFV) by
      transcranial Doppler ultrasound in 13 chronically hypercapnic, long-term
      ventilated patients with chronic obstructive pulmonary disease (COPD), in the
      following conditions: 1) breathing room air; 2) with oxygen supplementation; 3)
      during mechanical noninvasive intermittent positive pressure ventilation (nIPPV)
      with O2 enrichment. Under baseline conditions (room air), the CBFV was within the
      normal range. During oxygen administration, a statistically significant increase
      was obtained in Pa,O2 (6.5 +/- 0.6 vs 11.2 +/- 1.9 kPa (49.1 +/- 4.3 vs 84.3 +/-
      14.6 mmHg)), without relevant variations in: CBFV (54.2 +/- 9.1 cm.s-1), Pa,CO2
      (8.6 +/- 1.0 kPa (64.7 +/- 7.7 mmHg)) and hydrogen ion concentration [H+] (42.9
      +/- 2.9 nM), compared to baseline values (CBFV = 52.8 +/- 10.7 cm.s-1; Pa,CO2 =
      (8.4 +/- 0.9 kPa (63.1 +/- 7.1 mmHg; [H+] = 41.8 +/- 2.8 nM). After nIPPV, Pa,O2
      did not increase any further (10.6 +/- 1.7 kPa (79.2 +/- 12.7 mmHg)), while CBFV
      (40.9 +/- 12.6 cm.s-1), Pa,CO2 (7.5 +/- 1.3 kPa (56.2 +/- 9.4 mmHg)) and [H+]
      (39.1 +/- 4.6 nM) showed a significant reduction compared to oxygen therapy (p <
      0.01). We therefore conclude that in chronically hypercapnic long-term ventilated
      patients cerebral blood flow depends mainly on changes in Pa,CO2 and [H+], whilst
      oxygen does not seem to interfere with cerebral flow velocity. The reduction of
      Pa,CO2, due to mechanical ventilation, may determine cerebral blood vessel
      constriction, with possible impairment of cerebral functions.

PMID- 9151514
TI  - Comparison of endobronchial needle aspiration with forceps and brush biopsies in
      the diagnosis of endobronchial lung cancer.
AB  - Endobronchial forceps biopsy (FB) specimens of lung carcinoma are not uncommonly
      interpreted as nondiagnostic owing to extensive crush artefact, necrosis, or
      insufficient tissue. FB cannot be performed in some endobronchial lung cancers
      (EBLCs) with massive bleeding tendency due to fragility and friability.
      Cytological studies from the brushings and washings may also be unproductive,
      increasing the bronchoscopist's frustration. The aim of this study was to compare
      the diagnostic yield and complications of endobronchial needle aspiration (EBNA)
      with those of FB and brush biopsy (BB) in EBLCs examined by fibreoptic
      bronchoscopy. A prospective sequential study was carried out on 151 in-patients
      with EBLC. Bronchial aspiration (BA), EBNA and BB were performed in the patients
      with respiratory distress and with accompanying tumours of high bleeding
      tendency, completely obstructing main bronchi (Group 1: 68 patients). BA, EBNA
      and FB were performed in those with either central or peripheral EBLCs but
      without respiratory distress and/or significant bleeding tendency (Group 2: 83
      patients). In Group 1, the diagnostic yield of EBNA was found to be 90%, whereas
      that of BB was 66% (p < 0.05). In the same group, EBNA provided cell types in
      95%, compared with 88% by BB (p > 0.05). EBNA was diagnostic in 92% of Group 2
      patients, while FB established diagnosis in 78% of patients (p > 0.05). In
      determining cell type, no significant difference was found between EBNA (95%) and
      FB (97%) (p > 0.05). Regarding complications (only bleeding), there was no
      significant difference (p > 0.05) between EBNA (7%) and BB (13%), or between EBNA
      (4%) and FB (17%). We conclude that in endobronchial lung cancers: 1) the
      diagnostic yield of endobronchial needle aspiration is higher than brush biopsy;
      2) endobronchial needle aspiration increases the yield of brush biopsy when
      forceps biopsy cannot be performed owing to significant bleeding; 3)
      endobronchial needle aspiration increases the diagnostic yield when a forceps
      biopsy specimen is inadequate because of crush artefact, necrosis, or tissue
      resistance; and 4) endobronchial needle aspiration is as safe as brush biopsy and
      forceps biopsy.

PMID- 9151515
TI  - Breathlessness and control of breathing in patients with COPD.
AB  - We tried to verify, in a clinical setting, the hypothesis that enhanced
      perception of dyspnoea (PD) and increased respiratory drive (RD): 1) relate to
      each other; and 2) elicit an integrated response that leads to a decrease in RD
      and tidal volume (VT) aimed at minimizing PD. In 34 patients with chronic
      obstructive pulmonary disease (COPD), dyspnoea was graded on a four-point scale
      after a Medical Research Council (MRC) questionnaire concerning respiratory
      symptoms. Patients were divided into four groups according to the dyspnoea score.
      Pulmonary volumes, arterial blood gases, VT, respiratory frequency (fR),
      inspiratory time (tI), expiratory time (tE), maximal inspiratory pressure (MIP),
      and maximal expiratory pressure (MEP) were measured. RD was also assessed in
      terms both of mouth occlusion pressure (P0.1) and electromyographic (EMG)
      activity of the respiratory muscles. Increase in dyspnoea rating was associated
      with decrease in vital capacity (VC), forced expiratory volume in one second
      (FEV1), MIP, VT and tI; and increase in arterial carbon dioxide tension (Pa,CO2),
      P0.1, and EMG (analysis of variance (ANOVA) and Bonferroni's test). A rapid and
      shallow pattern of breathing (RSB) characterized the group with the highest
      dyspnoea rating. Stepwise multiple regression analysis showed that: 1) tI and
      FEV1 accounted for a substantial proportion of the variability in VT and tI,
      respectively; 2) VT and MIP, together, predicted a substantial proportion of the
      variability in Pa,CO2 (r2 = 0.50). We conclude that, in patients with chronic
      obstructive pulmonary disease clinical rating of dyspnoea appears to be
      associated with muscle weakness and increase in respiratory drive. The increased
      respiratory drive is modulated into a rapid and shallow pattern of breathing,
      which leads to hypercapnia.

PMID- 9151516
TI  - Bronchiolitis obliterans organizing pneumonia secondary to amiodarone: clinical,
      radiological and histological pattern.
AB  - The most common lung tissue reaction to amiodarone toxicity is a nonspecific
      pulmonary chronic interstitial pneumonia. In a minority of patients diffuse
      alveolar damage, alveolar haemorrhage or bronchiolitis obliterans organizing
      pneumonia (BOOP) is encountered. We report the case of a patient with clinical,
      functional, radiological and histological signs of BOOP secondary to amiodarone.
      The condition was partially reversible after suspending drug treatment, and
      resolved after corticosteroid treatment without relapse after a 14 month follow
      up.

PMID- 9151517
TI  - What is the appropriate use of the rapid diagnostic tests for tuberculosis?

PMID- 9151518
TI  - Interstitial lung disease: basic mechanisms and genetic predisposition.
AB  - Diffuse (interstitial) lung disease comprises a wide variety of relatively
      uncommon conditions, which present with characteristic clusters of clinical
      features and often with aberrant lung function. These diseases cause major
      morbidity and mortality due to lung injury and fibrosis. Some of these diseases
      are of known aetiology, whereas others are not. It has been suggested that the
      environment is a major contributing factor in this group of diseases. However,
      since not all individuals exposed to a common environment develop interstitial
      diseases, we can hypothesize that there is a genetic predisposition to their
      development. Therefore, if we can identify individuals who are genetically
      predisposed to develop diseases characterized by lung injury and fibrosis, then
      management strategies can be designed which will attempt to identify early
      disease and, in the longer term, to develop targeted genetic interventional
      approaches to treatment.

PMID- 9151519
TI  - Clinical diagnosis and assessment of obstructive sleep apnoea syndrome.
AB  - Obstructive sleep apnoea (OSA) syndrome is very common, affecting up to 4% of
      adult males. The pathophysiology of OSA is complex and incompletely understood,
      but upper airway (UA) obstruction appears to be the net result of an inability of
      the UA dilating muscles to maintain a patent oropharyngeal airway during sleep. A
      narrowed UA is common among OSA patients, and in adults this is usually due to
      nonspecific factors, such as fat deposition in the neck, or abnormal bony
      morphology of the UA. The present criteria for the diagnosis of OSA are not well
      defined, and different centres use different thresholds of apnoea and hypopnoea
      frequency during sleep to diagnose the clinical syndrome. The advent of many
      simplified diagnostic systems, some of which are portable and suitable for use in
      the patient's home, represents a major advance, but many of these systems are
      poorly validated, and there is no uniformity of measured variables among the
      various systems, apart from arterial oxygen saturation (Sa,O2). The established
      prevalence of OSA among the general population implies that most patients with
      suspected OSA should be initially assessed outside major sleep laboratories, in
      many cases by clinicians who may not have as detailed an understanding of the
      syndrome as clinicians who have undertaken specific training in sleep medicine.
      It is important, therefore, that clear-cut guidelines and criteria be established
      for the assessment and management of patients with suspected OSA.

PMID- 9151520
TI  - Causes of death in patients with COPD and chronic respiratory failure.
AB  - Although the factors associated with mortality, such as forced expiratory volume
      in one second (FEV1), arterial oxygen tension (Pa,O2) and pulmonary arterial
      pressure, have been well described, there is limited information on the
      circumstances of death in patients with chronic obstructive pulmonary disease
      (COPD). The aim of this study was to investigate the causes and circumstances of
      death in patients with COPD and chronic respiratory failure (Pa,O2 < 8.0 kPa (60
      mmHg) breathing air), treated with long-term oxygen therapy (LTOT). Ten European
      centres participated in the study and data were collected from patients both
      during a period of clinical stability and at the time of death. Of the 215
      patients evaluated (161 males and 54 females; aged 66 +/- 10 yrs), the major
      causes of death were: acute on chronic respiratory failure (38%); heart failure
      (13%); pulmonary infection (11%); pulmonary embolism (10%); cardiac arrhythmia
      (8%); and lung cancer (7%). Seventy five percent of patients died in hospital.
      There was no difference in the number of patients who died in the morning,
      afternoon and night hours. Twenty percent of the total died during sleep and in
      26% death was unexpected. A lower arterial carbon dioxide tension (Pa,CO2), less
      oxygen usage per 24 h, and increased incidence of arrhythmias were seen in those
      patients who died suddenly. Drug therapy was not related to unexpected death. The
      majority of patients with chronic obstructive pulmonary disease on long-term
      oxygen therapy died from chronic or acute on chronic respiratory failure.
      Prevention and treatment of respiratory failure in patients with chronic
      obstructive pulmonary disease is likely to have the greatest impact in reducing
      mortality.

PMID- 9151521
TI  - Multiple functions of alpha 1-antitrypsin and alpha 1-antichymotrypsin. 2. Role
      of serpins and their target enzymes in controlling neutrophil chemotaxis.

PMID- 9151522
TI  - Primary pulmonary hypertension: a continuing diagnostic and therapeutic
      challenge.
AB  - Primary pulmonary hypertension (PPH) continues to present both diagnostic and
      therapeutic challenges to the physician, reflecting the lack of understanding
      about the basic mechanism of the disease. The onset of the condition is usually
      insidious, the main symptoms of dyspnoea, syncope and angina often being ascribed
      to functional or emotional causes. As a result, delay in diagnosis is the norm,
      with an interval from onset of symptoms to diagnosis of up 2 yrs. The ability of
      the vasodilator drugs that are now available to produce sustained improvement in
      patients with PPH is limited by a number of factors. The prognosis is generally
      severe; however, despite the overall dismal prognosis, duration of survival
      ranges up to 10 years or more. It is important to consider the possibility of an
      early stage, when functional changes are prevalent in a substantial number of
      patients with primary pulmonary hypertension. At this stage, an optimized therapy
      would be expected to interrupt the course of pulmonary hypertension or, at the
      very least, retard its progression.

PMID- 9151523
TI  - Noninvasive mechanical ventilation and acute respiratory failure: indications and
      limitations.
AB  - Noninvasive mechanical ventilation (NMV) now represents the first step in the
      management of acute on chronic respiratory failure (A/CRF). During the last 5
      yrs, many studies have confirmed the feasibility of NMV in an acute setting,
      either by facial or nasal interface, used in addition to volumetric or barometric
      respirators, to manage A/CRF. The best indications for NMV are slowly progressive
      A/CRF, frequently represented by chronic obstructive pulmonary disease (COPD), or
      restrictive pulmonary disease. The criteria to initiate NMV in such patients are
      worsening of respiratory status and arterial blood gas (ABG) values, with
      increased hypoxia, hypercapnia and respiratory acidosis, despite optimal
      management with medication, physiotherapy and oxygen therapy. Respiratory
      encephalopathy is not an absolute contraindication; however, bronchial
      hypersecretion indicates that care is needed under NMV. Invasive mechanical
      ventilation with endotracheal (ET) intubation is discussed in the case of failure
      of NMV, when clinical status and ABG values worsen in spite of it. The signal for
      ET intubation is then obvious, represented by severe dyspnoea leading to
      respiratory pauses or arrest, severe cyanosis, and signs of haemodynamic
      instability. Despite immediate evidence of ominous cardiorespiratory
      inefficiency, ET intubation may be delayed and often avoided with the help of
      NMV. Criteria should be studied to identify guidelines for cessation of NMV, in
      order not to continue with the technique too long considering the safety of the
      patient. Indications for NMV in other kinds of ARF have received less study and
      are more controversial.

PMID- 9151524
TI  - Negative pressure ventilation in COPD patients with acute on chronic respiratory
      failure.
AB  - Negative pressure ventilators act by exposing the surface of the chest wall to
      subatmospheric pressure during inspiration. During negative pressure ventilation
      (NPV), tidal volume is related to the peak of the inspiratory negative pressure
      and the pressure waveform generated by the ventilator pump; for the same peak of
      negative pressure a square wave produces a greater tidal volume than a half sine
      wave. Several uncontrolled studies suggest that NPV may have a potential
      therapeutic role in the treatment of acute on chronic respiratory failure in
      patients with chronic obstructive pulmonary disease (COPD), reducing the need for
      endotracheal intubation. Recently, NPV has been used with a good outcome as a
      first-line treatment in COPD patients with severe acute respiratory failure and
      hypoxic hypercapnic coma. The positive results of these reports need to be
      confirmed by further controlled studies before recommending the generalized use
      of NPV in COPD patients with acute respiratory failure as standard care.

PMID- 9151525
TI  - Noninvasive pressure support ventilation: physiological and clinical results in
      patients with COPD and acute respiratory failure.
AB  - Noninvasive ventilation may bring considerable benefits in the treatment of acute
      respiratory failure, especially in patients with chronic obstructive pulmonary
      disease. Reduction in the need for endotracheal intubation has been well
      documented. In selected groups a reduction in morbidity, mortality, and length of
      hospital stay have been demonstrated. The efficacy of the technique is very
      dependent on the skill and motivation of the team.

PMID- 9151526
TI  - Physiological and clinical consequences of positive end-expiratory pressure.
AB  - The aims of positive end-expiratory pressure (PEEP) are: 1) in acute lung
      failure, to increase lung volume and to improve oxygenation; 2) in acute
      exacerbation of chronic obstructive pulmonary disease (COPD), to unload
      inspiratory muscles. Excessive levels of PEEP may increase the risk of
      barotrauma. Application of low levels of PEEP may replace intrinsic PEEP in acute
      exacerbation of COPD, without increasing lung volume; however, the haemodynamic
      consequences of PEEP must be taken into account.

PMID- 9151527
TI  - Scoring of severity in patients admitted to a respiratory intensive care unit.
AB  - A number of attempts have been made to develop measures of severity of illness
      for patients in the intensive care unit (ICU), but the impact of these indices in
      a Respiratory Intensive Care Unit (RICU) has not really been studied. At present,
      outcome can be accurately predicted in approximately 85% of ICU patients, while
      no data are available for the RICU. These indices will be reviewed in the
      article. The sophisticated Mortality Probability Model (MPM) II is used to
      predict the outcome of ICU patients. This technique is based on statistically
      derived weights for its variables. The "most popular" indices are the Acute
      Physiology and Chronic Health Education (APACHE), the Simplified Acute
      Physiological Score (SAPS) and the Therapeutic Intervention Scoring System
      (TISS). Overall, the predictive accuracy of the latest APACHE III equation and
      score is rather good, but there are important limitations concerning its use in
      the RICU. The SAPS includes 17 variables, and can be considered as a simplified
      version of APACHE sharing with it the same problems of application. The TISS
      requires data on approximately 70 treatment variables and assigns each a score
      ranging 1-4. A high score represents serious intervention, while a low score
      illness requires much less medical or nursing intervention. The sum of these
      scores indicates severity of illness because more critical patients are presumed
      to require higher levels of interventions. The RICU is also characterized by the
      use of noninvasive mechanical ventilation (NMV) in the treatment of acute
      respiratory failure. Some indices able to predict the success of NMV, have been
      developed recently during a brief trial of NMV, and included the level of
      acidosis and hypercapnia.

PMID- 9151528
TI  - Noninvasive mechanical ventilation in acute on chronic respiratory failure:
      determinants of success and failure.
AB  - Mechanical ventilation (MV) has been indicated in the treatment of acute
      respiratory failure (ARF) if conservative treatment fails. The recent innovations
      of noninvasive methods of mechanical ventilation (NMV) make it possible to avoid
      the complications of invasive MV, at the same time ensuring a similar degree of
      efficacy. A review of the literature from 1989 to 1996 shows that use of NMV in
      ARF has been reported in several studies involving more than 500 patients, mostly
      with chronic obstructive pulmonary disease (COPD). NMV was successful in 51-91%
      of cases, the severity of ARF being widely different among the different studies.
      Only three prospective, controlled, randomized studies compared the effectiveness
      of NMV with "conventional" medical therapy. Controlled studies of NMV versus
      endotracheal (ET) intubation are lacking. Success with NMV was associated with
      less severely abnormal baseline clinical and functional parameters and with less
      severe levels of acidosis assessed during an initial trial of NMV. Therefore, NMV
      may be useful in selected patients with ARF. Patients should have clinical and
      physiological evidence of ARF, and should be sufficiently co-operative. It is
      commonly said that NMV should be avoided and ET intubation performed in patients
      with haemodynamic instability, uncontrolled arrhythmias, gastrointestinal
      bleeding, or high risk for aspiration. With these limitations, NMV in selected
      patients with ARF is well-tolerated and may be useful in avoiding ET intubation
      in most cases of COPD, and with a wide range of success rates in other diseases.
      This in turn has several advantages in terms of avoiding complications of
      invasive MV, reducing the length of stay in the Intensive Care Unit (ICU), and
      probably the number of ICU readmissions. Side-effects of NMV appear less severe
      than those induced by invasive MV.

PMID- 9151529
TI  - Patient ventilator interfaces: practical aspects in the chronic situation.
AB  - In the ventilator-dependent patient, the nonpsychological problems of the chronic
      phase relate mainly to aspects of the patient ventilator interface.
      Humidification, suctioning of secretions, and ventilatory circuit and monitoring
      are the three most important aspects to which careful attention is needed. Good
      humidification can be obtained by means of various devices, which can provide
      humidity directly or indirectly: in the tracheostomized patient, the heat and
      moisture exchanger appears to be a good method because of its antibacterial
      properties. Airway suctioning is frequently needed in patients receiving
      ventilation invasively. Suctioning of secretions might possibly be associated
      with the risk of major cardiorespiratory complications: bacterial colonization of
      the airways and the subsequent increased risk of infection should be carefully
      considered. Problems concerning the ventilatory circuit and monitoring can be
      specific in patients with a tracheal cannula and those with a nasal/facial
      interface. Long-term tracheostomy in itself represents a real risk for bacterial
      colonization, damage to the tracheal mucosa, and to functioning of the vocal
      cords (both for speech and swallowing): therefore, a switch from invasive to
      noninvasive ventilatory interface may be proposed. Most problems with the nasal
      mask interface concern air leakage and the skin mucosal lesions. Two major
      aspects must be taken into account when considering the long-term effects of
      noninvasive ventilatory support monitoring: the possible effect of CO2
      rebreathing, and the inadequate volume/pressure delivery, so that proper
      ventilation cannot be achieved. Use of an oral/mouth interface is of limited
      interest in subjects with restrictive disorders: air gastric distension and
      orthodontic problems are the most common side-effects in chronic use.

PMID- 9151530
TI  - Where and how must we perform noninvasive mechanical ventilation?
AB  - The classic experience of mechanical ventilation (MV) has recently been
      integrated with the use of devices providing noninvasive ventilatory assistance
      in the Intermediate Intensive Care Unit (IICU), to which patients suffering from
      acute on chronic respiratory insufficiency may be admitted for therapy.
      Noninvasive mechanical ventilation (NMV) has been demonstrated to be mandatory
      during severe relapses of chronic obstructive pulmonary disease (COPD). This
      method of ventilation can reduce mortality, morbidity and time spent in the
      Intensive Care Unit (ICU) when related to standard medical therapy alone. NMV
      should be considered for routine care in selected patients after optimization of
      the delivery system and education of personnel. An ideal monitoring system during
      MV is important to patient management. It must present interpretable data, high
      technical accuracy, high sensitivity, good reproducibility, be practical to use,
      be of low risk to the patient and inexpensive. During acute relapses of COPD in
      patients who require MV, malnutrition and a multifactorial score (Acute
      Physiology and Chronic Health Evaluation (Apache) II score) has been shown to be
      poor and an unfavourable index of outcome. Specific standards for the IICU are
      necessary, in terms of location, ventilators used, and a training programme in
      intensive care medicine. Dedicated pulmonary intensivists and nurses should be
      trained to have a comprehensive theoretical knowledge of the field of intensive
      respiratory care. COPD patients are the usual candidates for frequent admissions
      and prolonged stays in the ICU. Advanced COPD may frequently need periods of
      intensive treatment, monitoring and nursing. These patients may benefit from NMV
      which provides a specific intermediate treatment. With regard to an optimal
      cost/benefit ratio, the IICU is a reasonable alternative for COPD patients with
      less severe acute respiratory failure (ARF), reducing superfluous ICU stays.

PMID- 9151531
TI  - Markers of acute airway inflammation.
AB  - In asthma, acute inflammation induced by allergen challenge in allergic patients
      leads to an early and a late phase reaction. Immunoglobulin E (IgE)-mediated cell
      activation plays a crucial role in acute inflammation and leads to the release of
      proinflammatory mediators, such as histamine, eicosanoids, platelet-activating
      factor, oxygen-free radicals, neuropeptides and cytokines. These mediators are
      capable of inducing constriction of airways smooth muscle, increased secretion of
      mucus, and vasodilatation, as well as several important biological events,
      including modulation of the expression of adhesion molecules in endothelial and
      epithelial cells, and of inflammatory cell recruitment. Clinically, acute airway
      inflammation is characterized by a bronchoconstrictive response with acute
      symptoms, including wheezing and dyspnoea which can be reversed by short-acting
      bronchodilators, among which beta 2-agonists play a major role.

PMID- 9151532
TI  - Knowledge of inflammatory cytokines and mediators in asthma: what is its
      importance in clinical practice?

PMID- 9151533
TI  - Non-Hodgkin's lymphoma with rheumatism-like presentation and multiple cystic and
      nodular lesions in the liver.
AB  - We report the case of a non-Hodgkin's lymphoma in an isolated and not previously
      diagnosed "adult polycystic liver disease". In this case, a rheumatism-like
      presentation was associated with the discovery of multiple nodular and cystic
      lesions in the liver. Of these, the former were related to lymphoma involvement,
      the latter to pre-existent liver disease. The singularity of the case, not
      previously reported, and some difficulties met in diagnosing the two pathologies,
      justify the report.

PMID- 9151534
TI  - Study on the suitability of sow colostrum for the serological diagnosis of
      porcine reproductive and respiratory syndrome (PRRS).
AB  - Serum and colostrum from 73 sows were collected. The serum samples were tested by
      Immuno. Peroxidase Monolayer Assay (IPMA) and the corresponding colostrum samples
      with the indirect Immuno fluorescent Antibody (IFA) technique. All serum positive
      sows were colostrum positive and all colostrum negative were serum negative.
      Eight sows only reacted positively in the colostral testing. Compared to the
      serum standard test the specificity was 82.6% and the sensitivity 100%. The
      observed agreement between both tests was 89.2%. In addition all serum samples
      were also tested with the IF test (IFT). Of the eight sows which were negative in
      the IPMA serum test and positive in the IFA colostrum test, three were found
      positive when the serum was tested with IFA. Consequently, the observed agreement
      was higher at 93.2%. After the suitability of colostrum for porcine reproductive
      and respiratory syndrome (PRRS) diagnosis was demonstrated, 1915 colostrum
      samples collected from 135 different farms were tested in a comparative study
      with the IPMA and IFA techniques. Of the 1915 colostrum samples 139 were positive
      with both IPMA and IFA. With IPMA only, 43 samples were positive compared with
      192 samples found positive with the IFA technique. A total of 1541 samples were
      negative in both tests. The observed agreement between both tests was 87.5%. The
      quotient of the observed agreement minus chance agreement and the maximum
      possible agreement beyond chance level (Kappa Quotient) was 0.49. In 90% of the
      farms that tested IFA positive there was a seroconversion of more than 50% of all
      colostrum tested. By comparison only 29% of the IPMA positive farms were positive
      with more than 50%. Based on the epidemiological findings on PRRS it was
      concluded that the IFA technique indicates a higher sensitivity for the detection
      of PRRS virus antibodies in sow colostrum. Finally the possible advantages and
      disadvantages of sow colostrum testing and serum testing are discussed.

PMID- 9151536
TI  - Bacteria associated with enzootic pneumonia in goats.
AB  - A histological and microbiological study of lung samples from 83 slaughtered
      goats (33 kids and 50 adults) drawn from a flock with a history of
      pleuropneumonia caused by mycoplasmas of the M. mycoides group was carried out. A
      total of 82% (27/33) of kids and 36% (18/50) of adult goats presented pulmonary
      lesions characteristic of enzootic pneumonia: lesions took the form of
      bronchointerstitial pneumonia with peribronchial and peribronchiolar
      proliferation of lymphocytes. Microbiological analysis confirmed a range of
      mycoplasma species, including Mycoplasma mycoides ssp. mycoides Large Colony
      (MmmlC) (3.70%; 1/27), Mycoplasma mycoides ssp. capri (Mmc) (7.40%; 2/27),
      Mycoplasma putrefaciens (22.2%; 6/27), Mycoplasma arginini (3.70%; 1/27) and
      Mycoplasma sp. (7.40%; 2/ 27), as well as Pasteurella multocida (14.8%; 4/27),
      associated with enzootic pneumonia lesions in younger animals, whereas Mycoplasma
      sp. was associated with enzootic pneumonia in adult goats (22.0%; 4/18). Cilia
      associated respiratory (CAR) bacillus found by histochemical examination was
      associated with enzootic pneumonia in kids (25.9%; 7/27) and goats (44.4%; 8/18),
      being the first description of this bacterium in adult goats.

PMID- 9151537
TI  - Ultrastructural findings in natural canine hepatozoonosis.
AB  - The ultrastructure of several stages of Hepatozoon canis found in dogs with
      clinically and histologically diagnosed infections was determined using
      transmission electron microscopy. Merozoites, macro- and microschizonts and
      gamonts were found in spleen, liver, kidneys and lungs. Macro- and micromeronts
      were characterized by their size and by the presence of intracytoplasmic
      amylopectin granules. Gamonts, which provide the basis for clinical diagnosis of
      the disease, were observed within mononuclear cells (monocytes/macrophages); they
      were butterfly-shaped and exhibited varying electron densities. On the basis of
      the microscopic observations reported here, it is clear that the life cycle of H.
      canis is a complex one.

PMID- 9151538
TI  - The nature of periodontal diseases.
AB  - Periodontal diseases are infections. They have a number of properties in common
      with infections in other parts of the body, but have unique features resulting
      from the passage of the tooth through the soft tissue integument into the oral
      cavity. The tooth provides a solid, non-shedding surface for the colonization of
      potentially pathogenic bacterial species as well as a wide range of host
      compatible species. Periodontal pathogens frequently colonize the periodontal
      area for prolonged periods of time prior to disease initiation. Disease is caused
      by a finite set of bacterial species leading to the development of multiple
      periodontal diseases. Disease occurs at individual periodontal sites and leaves
      an historical record of the damage to the periodontium in the form of periodontal
      attachment or bone loss. This feature provides difficulty in investigation since
      it is often unclear whether the infectious process is presently occurring or is a
      reflection of past destruction. Control of periodontal diseases is most
      effectively performed by eliminating or suppressing the organisms that cause them
      and establishing a host compatible microbiota. When tissue damage has been
      extensive, regenerative or replacement procedures should be instituted after the
      infection has been controlled.

PMID- 9151535
TI  - Characterization of a large transferrin-binding protein from Actinobacillus
      pleuropneumoniae serotype 7.
AB  - The binding of transferrin at the surface of Actinobacillus pleuropneumoniae (A.
      pp.) is mediated by two proteins of approximately 60 and 100 kDa. The 60 kDa
      protein has been shown to be highly divergent among different serotypes and to
      induce a serotype-specific protective immune response. In this study we have
      characterized the 100 kDa transferrin-binding protein of A. pp. serotype 7 and
      designated it as TfbB. The tfbB gene was found to be located immediately
      downstream of the tfbA gene. It was cloned and sequenced, and antibodies raised
      against the isolated recombinant protein detected, with a constant intensity, a
      100 kDa protein in A. pp. serotypes 2, 4, 6, 7, 8, 9, 10 and 11, and a
      polypeptide of approximately 103 kDa in serotypes 1, 3, 5A and 12. In addition,
      comparative analysis of the deduced amino acid sequence showed more than 40%
      identity with the large transferrin-binding proteins of Neisseria meningitidis
      and Haemophilus influenzae. The TfbB protein was expressed in E. coli outer
      membranes in a conformation eliciting porcine transferrin-specific binding
      activity. Sera of pigs immunized with these TfbB-containing E. coli membranes
      recognized functional membrane-associated TfbB protein whereas no such reaction
      was observed upon immunization with isolated recombinant TfbB protein. A
      preliminary animal experiment showed that TfbB-containing outer membrane
      preparations from recombinant E. coli can reduce significantly the mortality of
      an A.pp. infection with the homologous strain.

PMID- 9151539
TI  - An overview of Food and Drug Administration regulation of drugs, biologics, and
      devices to be used for management of periodontal diseases.
AB  - The Food and Drug Administration (FDA) has been actively involved in assuring the
      safety and effectiveness of medical products since 1906. The FDA was granted
      increased authority to regulate drugs in 1938 and devices in 1976. The regulatory
      requirements for marketing in the United States vary according to the type of
      product and the degree of risk associated with it. One route to the market is
      through the premarket notification [510(kappa)] process in which devices are
      evaluated according to their substantial equivalence to devices marketed prior to
      May 28, 1976. Many devices specifically intended to treat periodontal conditions
      have progressed through the 510(kappa) process based on their substantial
      equivalence to predicate devices. In some cases manufacturers have needed to
      provide clinical data in the form of Investigational Device Exemptions (IDE) to
      support an equivalence determination. Certain devices with indications for use in
      periodontal evaluation or therapy, specifically, those determined by FDA to be
      not substantially equivalent to legally marketed devices, require Premarket
      Approval Applications (PMA). For new drug products, clinical trials are carried
      out under an approved Investigational New Drug Application (IND). Application for
      approval for marketing is requested through a New Drug Application. Data from
      clinical trials conducted outside the United States may be considered by the FDA
      in support of the safety and effectiveness of the product. The FDA is continually
      developing and updating guidance documents and guidelines to assist manufacturers
      in gaining clearance/approval to market new products.

PMID- 9151540
TI  - International regulatory aspects of clinical periodontal research.
AB  - The Food and Drug Administration (FDA) was the pioneer regulatory agency to set
      standards for clinical studies aimed at approval of new drugs. For years the
      FDA's rules represented the most thorough, stringent, and consistent policy. Now
      most other developed countries have comparable requirements for the conduct of
      clinical trials. The European Community (EC). Canadian, and Japanese regulations
      are most important for United States (US) scientists attempting to globalize
      their research. Regulations in Eastern Europe, some Asian countries, and Latin
      America are of growing importance. The Pacific-Rim appears to be the fastest
      growing pharmaceutical market in the next decade. Currently, the EC and Japan's
      Good Clinical Practice (GCP) regulations are more detailed than those of the US.
      Moreover, the World Health Organization recently published GCP recommendations
      similar to the EC requirements. Well-designed and well-controlled studies done in
      the EC, US, and other developed countries are generally accepted throughout the
      world. Japan and some other countries require studies in local patients. American
      scientists cannot expect to conduct studies in other countries as principal
      investigators, but many are associated with national clinicians. Mutual
      recognition of marketing approvals is the ultimate goal for the globalization of
      drug research. While it is the objective of the Scheme for the Mutual Recognition
      of Evaluation Reports on Pharmaceutical Products and the EC Decentralized
      Procedure, it is not apparent when the FDA will totally accept another regulatory
      body's approval decision. The International Conference on Harmonization involves
      the EC, Japan, and the US. This most important series of meetings will finally
      align the major countries more closely in regulating clinical studies and the
      production of safe, effective, and quality products, especially in these times of
      worldwide economic considerations and health care reform. It is imperative that
      US dental scientists become more familiar with pertinent regulations in leading
      foreign countries.

PMID- 9151541
TI  - Voluntary programs: ADA Seal program and international implications.
AB  - For about 130 years the American Dental Association (ADA) has aided the
      profession and the public in selecting safe and effective dental products. Since
      1930, dental products have been evaluated through the ADA Seal program. In
      accordance with the ADA's Bylaws, the Council on Scientific Affairs assesses
      information evaluating the safety, efficacy, appropriate use, and promotional
      claims of dental products. In doing so, the Council may award the ADA's Seal of
      Acceptance. In collaboration with interested parties, expert consultants, and
      Council members, the ADA produces guidelines suggesting appropriate methodologies
      and submission data to assist manufacturers in voluntarily earning the Seal of
      Acceptance. To date, numerous professional and consumer products have been
      evaluated, and about 1,300 of these products bear the Association's Seal of
      Acceptance. When a product is awarded the Seal it means that adequate data have
      been submitted and reviewed and, based on available information, the product
      meets ADA guidelines of safety and effectiveness. Dental health care
      professionals and consumers who use products that have the Seal can be confident
      that a product's properties and performance are consistent with current
      professional standards and manufacturers' claims. The ADA Seal program serves to
      help dentists and manufacturers meet their ethical obligations to the public by
      promoting safe and effective health care products.

PMID- 9151543
TI  - Subject recruitment, retention, and compliance in clinical trials in
      periodontics.
AB  - Recruitment of subjects in randomized controlled trials is the process of
      screening and enrolling a predetermined number of subjects within a planned time.
      Differences between projected and actual recruitment rates are common and, when
      large, form a serious threat to the successful completion of the trial.
      Recruitment can be enhanced by 1) use of different, concurrent recruitment
      methods; 2) avoiding underestimations of the costs and time intensity of subject
      recruitment; and 3) regular monitoring of the efficiency of the recruitment
      effort. The recruitment process can be complicated by legal requirements of
      proper representation of sex and race characteristics or by stringent entry
      criteria. Complex designs (e.g., trials with a pre-randomization placebo run-in,
      split-mouth designs) have not yet shown to be cost-effective and may endanger
      recruitment success. Enhancing both subject retention and protocol compliance
      requires careful planning, attention to product design and staff training. The
      impact on trial findings is discussed.

PMID- 9151542
TI  - Design principles and statistical considerations in periodontal clinical trials.
AB  - Although clinical trials are a small subset of conducted biomedical research,
      they have become powerful investigational tools for the evaluation and approval
      of new treatments by clinician groups and regulatory agencies like the US Food
      and Drug Administration. To impact the delivery of care, trials in general must
      meet three criteria: clarity, comparability, and generalizability. Accordingly,
      trials can offer meaningful data if they have procedures which are well defined
      and subjects who represent a reasonably homogeneous population. The evaluation of
      periodontitis interventions presents several challenges due to the disease's
      heterogeneity and its irregular, episodic pattern; nevertheless, the intent of
      these novel interventions is to prevent, diagnose, inhibit, or reverse
      periodontal disease progression. Careful consideration of the trial's objectives
      should dictate clinical endpoints (primary and surrogate), comparison groups
      (placebo, standard therapy, test therapy), and equivalence versus superiority as
      the basis for conclusions. Several design elements such as control population
      specification, randomization, masking, sample size calculation, and
      standardization of procedures for patient care and assessment can decrease
      potential bias and variability. In both parallel and paired (split-mouth) design
      trials, multiplicities of endpoints, treatments, and subgroups require strategies
      which address the broader scope of chance findings without excessive loss of
      study power. Also, the longitudinal assessment of multiple periodontal sites
      within patients produces correlated data structures for which analytic methods
      need to account for the appropriate sampling unit. With these design and analytic
      elements, clinical trials can provide important evidence to investigators,
      patients, and governmental agencies for the introduction of novel interventions
      in periodontal practice.

PMID- 9151544
TI  - The research team, calibration, and quality assurance in clinical trials in
      periodontics.
AB  - The present report provides an overview of practical issues related to training,
      calibrating, and monitoring the individuals involved in conducting a clinical
      trial. These aspects are considered in relation to a theoretical multi-center
      clinical trial designed to test the safety and efficacy of a new periodontal
      treatment. Many factors need to be controlled in order to reduce inherent
      variability and provide standardization across the study population and study
      centers in a large-scale multi-center clinical trial. Components incorporated to
      control these factors include identification and recruitment of study centers,
      pre-study training and organization of the teams at the different research
      centers, quality assurance procedures and monitoring of the study for compliance
      with protocol and safety requirements, and management of databases. Details are
      given regarding the use of pre-study survey questionnaires to assess research
      center capabilities, methods for training and calibrating examiners and
      therapists and methods for integrating these aspects prior to actual study
      commencement, and quality assurance after the study has begun. The review
      considers the critical practical details regarding all of these aspects of study
      organization and execution.

PMID- 9151545
TI  - Randomized clinical trials in periodontology: ethical considerations.
AB  - Ethical justification for starting a clinical trial requires at the outset an
      accurate statement of "no difference" regarding the two or more agents to be
      compared. This may be expressed as "theoretical equipoise" (no data to support
      the superiority of one of the agents) or, preferably, as "clinical equipoise"
      (there are insufficient data to resolve controversy among experts as to which is
      superior). This presents a problem when a placebo control is proposed,
      particularly when the outcome measure entails irreversible loss of function;
      preliminary data often suggest the superiority of the "active agent." Informed
      consent should ordinarily include the fact that treatment assignments will be
      accomplished by a process of randomization and, in the case of double-blind
      designs, that neither the subject nor the investigator will know the subject's
      treatment assignment until the end of the trial. In general, clinical trials
      should be monitored by data and safety monitoring boards that have access to
      unblinded data; they should be guided by stopping rules that should be agreed
      upon by all concerned before the trial is begun. Women and minorities must be
      included unless there is strong justification for their exclusion. Care must be
      taken to balance the competing objectives of validity (the results will be
      correct), generalizability (the results will be broadly applicable), and
      efficiency (the study will not be unduly expensive).

PMID- 9151546
TI  - Overview of clinical trials of periodontal diagnosis methods and devices.
AB  - Changing views of the pathogenesis and progression of the periodontal diseases
      and new modalities for treatment have stimulated a plethora of physical,
      biochemical, microbiologic, and immunologic diagnostic procedures, tests, and
      devices. Clinical trials address needs for: 1) screening tests and risk
      assessment for disease susceptibility; 2) identification of active and
      progressive disease sites; 3) making therapeutic decisions; 4) monitoring
      therapy; 5) establishing a maintenance schedule; and 6) prognosis assessment.
      Needs and priorities of general, specialty, and public health practitioners
      differ. Validation of tests proceeds in a hierarchy of study designs from cross
      sectional and case control studies to retrospective and prospective longitudinal
      multi-center trials. For broad-scale application, randomized controlled trials
      (and eventual meta-analysis) will be required. Design issues are those common to
      all clinical trials in periodontics plus special considerations depending on type
      of test and its intended use. For diagnostic tests, recommended surrogate
      endpoints are attachment and alveolar bone levels-the traditional "gold
      standards." Validation of diagnostic tests is best accomplished by generation of
      2 x 2 contingency tables to calculate sensitivity and specificity, positive and
      negative predictive values, relative and absolute risks, and odds rations. Each
      has a place-depending on the clinical situation and needs of the clinician.

PMID- 9151547
TI  - Regulatory issues unique to clinical trials on periodontal diagnostic methods and
      devices.
AB  - A wide variety of in vitro diagnostic products have been proposed for use in
      patients with periodontal disease. The Food and Drug Administration (FDA) review
      focuses on three important issues. First, the product must exhibit acceptable
      analytical performance (accuracy, precision, analytical sensitivity, and
      analytical specificity). Second, the effectiveness of the device must be clearly
      defined. The studies required to establish this will depend largely on the
      proposed intended use of the product. At a minimum, clinical or diagnostic
      sensitivity and specificity should be established. Finally, the product must meet
      the labeling requirements for in vitro devices. These requirements outlined in
      CFR 809.10(b) are comprehensive and cover 15 key elements including information
      about the principles of the analytical method; handling of instruments, reagents,
      and patient samples; test limitations; and test performance. Applicants
      developing products for any in vitro diagnostic device are encouraged to review
      the labeling regulations along with other divisional and office guidance material
      to help in defining the submission requirements. The FDA is willing to meet and
      work with companies prior to and during preclinical and clinical trials to assist
      in the development of appropriate study protocols.

PMID- 9151548
TI  - The use of periodontal probes and radiographs in clinical trials of diagnostic
      tests.
AB  - Periodontal probing attachment level measurements and intraoral radiographs are
      used to assess the level of the clinical attachment and bone support in the
      diagnosis of periodontitis. Together these physical measurements of tooth support
      comprise the standard against which new diagnostic tests are compared. Since
      probing and radiographs provide a measure of the severity of attachment or bone
      loss at one point in time, serial measurements must be compared to determine
      whether periodontitis is progressive. Periodontal probing may be performed
      manually or by using controlled force electronic instruments. The resolution,
      depending on the instrument, will vary from 1.0 mm to 0.1 mm. Variations in
      probing force, size and shape of tip, location of tip placement, detection or
      reference landmarks for attachment level probing, degree of gingival
      inflammation, and transcription may adversely influence accuracy. Electronic
      probes offer the advantage of improved resolution, force control, and automatic
      recording, but the literature is inconsistent about the advantages in terms of
      repeatability and accuracy. Radiographic assessment of alveolar bone loss may be
      achieved by visual interpretation, measurement, or digital image analysis. While
      visual interpretation of unstandardized radiographs is insensitive to changes in
      bone, standardized radiographs can permit measurement of changes on the order of
      0.2 mm when computerized methods are used. Newer techniques such as digital
      subtraction radiography permit detection of bony changes too small to be seen by
      the unaided eye and are over 95% sensitive and specific in detecting bony changes
      less than 10 mg.

PMID- 9151549
TI  - Evaluation of components of gingival crevicular fluid as diagnostic tests.
AB  - Gingival crevicular fluid (GCF) is an inflammatory exudate that can be collected
      at the gingival margin or within the gingival crevice. The biochemical analysis
      of the fluid offers a noninvasive means of assessing the host response in
      periodontal disease. In recent years, the relationship of measures of the
      inflammatory response in GCF to risk for development of active periodontal
      disease (defined as clinical attachment loss or radiographic bone loss) has been
      studied in longitudinal trials. The greatest interest has focused on
      prostaglandin E2, an arachidonic acid metabolite; beta-glucuronidase and
      neutrophil elastase, markers of lysosomal enzyme release from neutrophils; and
      aspartate aminotransferase, a cytoplasmic enzyme indicative of cellular necrosis.
      Analysis of the data allows a number of conclusions to be drawn concerning the
      potential diagnostic significance of GCF: 1) an exuberant host inflammatory
      response is associated with progressive disease in patients with periodontitis;
      2) collection of GCF using small precut strips is a reproducible and reliable
      collection technique; 3) the total amount of the mediator and not concentration
      of the mediator in the GCF sample can be reported when timed samples are
      collected; and 4) technology exists for GCF-based diagnostic tests to be
      performed in the dental office. Nevertheless, many questions remain. Still to be
      determined are: 1) the relationship of test results to the development of
      periodontitis in patients with gingivitis; 2) the level of test accuracy needed
      to justify use of these tests; 3) the unit of observation (patient, site) that is
      being evaluated by the test; and 4) the need for such tests as perceived by
      clinicians. While these questions are formidable, introduction of GCF-based
      diagnostic tests will provide clinicians with an improved, quantitative means of
      evaluating patients and offer specific criteria to assess the effectiveness of
      treatment.

PMID- 9151550
TI  - Principles of evaluation of the diagnostic value of subgingival bacteria.
AB  - This paper describes steps in the process of evaluating subgingival bacteria
      assays for the diagnosis of periodontal disease. The first step examines the
      infectious etiology of periodontal disease in pointing to specific oral bacteria
      as periodontal pathogens. Second is characterization of the laboratory test to
      detect and quantitate these pathogens as to sensitivity, specificity, and
      positive and negative predictive value. Third is the role of the laboratory test
      in the diagnosis of the different forms of periodontal disease which is related
      to the current clinical rather than microbiological definition of these diseases.
      The fourth and most important step is an analysis of the significance of
      subgingival bacterial tests in clinical decision-making.

PMID- 9151551
TI  - Overview of periodontal clinical trials utilizing anti-infective or host
      modulating agents.
AB  - Issues in periodontal trials designed to evaluate anti-infective or host
      modulating agents for the prevention and treatment of periodontal diseases are
      reviewed in this paper. Clinical trial designs, prevention versus treatment,
      disease activity, utility of new measurement technologies, ethical and safety
      issues, selection of outcome variables, and clinical significance are discussed.
      In general, randomized parallel arm, double-blinded, controlled clinical trials
      are most appropriate for testing anti-infective and host modulating agents. New
      measurement technologies may offer increased measurement resolution and automated
      data capture; but, depending on their specific application and level of examiner
      reproducibility, these technologies may or may not result in lowered thresholds
      for declaring change. Mechanical therapy for common plaque-associated gingivitis
      and adult periodontitis is effective, has low risk, and is widely accepted as a
      minimum standard of care. New agents for treatment of these diseases must carry
      minimal risk and have equal or greater effectiveness than this standard of care.
      Outcome variables for gingivitis trials should include a visual index of gingival
      inflammation and a separate or component index of gingival bleeding. Prevention
      studies of periodontitis require a longer duration than treatment studies.
      Maintenance of mean clinical attachment level should be a primary outcome measure
      for all prevention studies of adult periodontitis. Maintenance of alveolar bone
      support is an essential additional outcome for agents specifically acting on
      bone. The design and conduct of clinical trials for anti-infective and host
      modulating agents depend on the specific hypothesis to be tested and the ethical
      demands of providing safe and effective care for all study volunteers.

PMID- 9151552
TI  - Regulatory issues for evaluation of therapies to prevent or arrest disease
      progression.
AB  - The Federal Food Drug and Cosmetic Act gives authority to the US Food and Drug
      Administration (FDA) to regulate foods, human and veterinary drugs, biological
      products, and cosmetics which are to be introduced into interstate commerce. The
      approval of pharmaceutical products for the treatment and/or prevention of
      periodontal diseases requires presentation of evidence that supports the safety
      and efficacy of the particular drug therapy in question. Sponsors need to
      carefully consider each step in the overall development plan beginning with an
      Investigational New Drug Application and concluding with submission of a New Drug
      Application for pre-market approval. This paper focuses specifically on the
      design, conduct, and analysis of clinical trials of drugs for the prevention or
      treatment of periodontal diseases. It is based upon a guidance document under
      development at the time of this presentation by FDA's Center for Drug Evaluation
      and Research that will include separate chemistry, toxicology, and
      biopharmaceutics sections. Unlike more formal FDA guidelines, a guidance document
      can be more easily and regularly updated to reflect changes in the state of the
      art of periodontal diagnosis and treatment.

PMID- 9151553
TI  - Design and implementation of clinical trials of antimicrobial drugs and devices
      used in periodontal disease treatment.
AB  - The design and implementation of clinical trials (CTs) carried out to evaluate
      antimicrobial and anti-infective drugs and devices are one of the most difficult
      challenges in contemporary periodontal research and product development. The
      overwhelming amount of evidence which has established a microbial etiology for
      periodontitis is the basis for developing and testing antimicrobial treatments.
      Well-designed antimicrobial CTs start with a carefully crafted hypothesis and a
      protocol which explicitly integrates the requirements of the patient, the
      clinician, the sponsor, and regulatory authorities. Surrogate variables for
      effectiveness must be clinically relevant, scientifically sound, and
      statistically valid. Currently, clinical attachment level measurements and
      alveolar bone assessments are accepted as proof of effectiveness. Indication and
      claim support of the antimicrobial product guide the design and implementation of
      the CT. Adverse microbiologic consequences, such as lack of antimicrobial
      susceptibility, wrong spectrum, incorrect dosage, non-compliance, and drug
      interference, must be monitored. Successful CTs balance a large group of
      variables used to screen, randomize, and assign subjects to experimental and
      control groups to ensure that prognostic and risk factors are properly accounted
      for.

PMID- 9151554
TI  - The design and implementation of trials of host modulation agents.
AB  - Over the last two decades it has become more evident that although oral
      microorganisms are essential agents of periodontal pathogenesis, interpatient
      variability in the host response is a major determinant of the expression of
      periodontal disease extent and severity. Data from animal models and human
      studies have identified many of the components of the host inflammatory response
      which serve as critical mediators of clinical inflammation, attachment loss, and
      bone resorption. Studies suggest that certain pharmacologic agents, which act at
      a molecular level to block specific inflammatory mediators, appear to attenuate
      disease progression. These promising findings herald a new era in periodontal
      medicine. Anti-infective therapies may soon be supplemented with anti
      inflammatory pharmacological agents. However, there are many unanswered issues
      regarding formulation design, clinical application, potential indication claims,
      and clinical study design. Furthermore, current considerations of fundamental
      mechanisms of pathogenesis, as well as new data from epidemiologic studies
      emphasizing the multifactorial nature of disease, are changing the underlying
      assumptions which have served to guide our design of anti-infective drug trials
      over the last two decades. There are new questions regarding appropriate outcome
      measurements which are to be reconsidered. For example, the measurement of a
      change in periodontal disease status, either during progression or in response to
      therapy, is fundamentally unidimensional and may be only mildly informative when
      one considers that the disease is multifactorial by nature. Using an example from
      intensive care medicine, pathophysiologic studies of septic shock have
      demonstrated that the microbial dose and the host inflammatory mediator response
      are far better predictors of patient morbidity and mortality than any combination
      of clinical signs associated with clinical shock. Clinical trials of anti
      cytokine and anti-inflammatory drugs to treat shock are now designed and
      conducted taking strategic advantage of this knowledge by including measurements
      of microbial dose and host response. It appears prudent that the design and
      implementation of clinical trials of host modulation agents also benefit from our
      current insights into pathogenesis and not represent a template-driven adaptation
      of historical, anti-infective clinical trial protocols.

PMID- 9151555
TI  - Overview of clinical trials on periodontal regeneration.
AB  - Periodontal regeneration means healing after periodontal surgery that results in
      the restoration of the tooth-supporting tissues; namely, cementum, alveolar bone,
      and periodontal ligament. The response of the periodontium to conventional
      periodontal flap surgery is primarily repair. Regenerative flap procedures
      involve modifications intended to alter variables in the normal wound healing
      response to shift the outcome from repair to regeneration. Technical
      manipulations, devices, pharmacological agents, and biologicals have been used to
      obtain regeneration. Evaluation of periodontal therapy is done by clinical and
      histological assessments. Human clinical trials depend on probing, re-entry, and
      radiographic measurements which cannot distinguish between periodontal repair and
      regeneration. Histological studies are difficult in humans because they require
      the retrieval of tissue blocks containing the teeth and their surrounding
      tissues, and for this reason these studies have largely been done in animal
      models; however, the use of animal models creates problems of interpretation when
      applying the information to the human. There are other fundamental problems
      related to assessment of new methods of periodontal regeneration. Ideally,
      periodontal regeneration is attempted after resolving the periodontitis that
      produced the loss of periodontal support. Does the type of periodontal disease
      affect the outcome? If it does, then separate clinical trials would be indicated
      to manage defects produced by different diseases. Furthermore, certain types of
      periodontal defects apparently respond better than others (for example, intrabony
      defects versus suprabony defects). Does each type of defect require a separate
      trial? Do subjects respond differently and, if so, how should this be factored
      into selection of the study population and sample size? There appear to be more
      questions than answers concerning the design of clinical trials for periodontal
      regeneration. This is not surprising since regeneration has been possible for
      only a few years, is apparently unpredictable, and the origin and nature of the
      new tissue are poorly understood. These factors make it important that the design
      of clinical trials be openly and thoroughly discussed so that practical solutions
      are forthcoming.

PMID- 9151556
TI  - Regulatory issues relating to therapies for periodontal regeneration.
AB  - The Food and Drug Administration (FDA) has regulated medical devices since May
      1976, when the Medical Device Amendments were enacted. The clinical trial
      requirements for the marketing of periodontal regeneration devices have been
      dependent, in part, on the degree of their similarity to devices marketed prior
      to the legislative enactment date in terms of materials, indication statements,
      and labeling claims. Nonresorbable barriers were allowed to be marketed based on
      their equivalence to devices marketed prior to the enactment date based on
      biocompatability and clinical trial data under the premarket notification
      requirements section of the law. Bone filling materials such as hydroxyapatite
      were first marketed based on the finding of equivalence to predicate devices.
      Newer technologies such as bioabsorbable barriers have also been reviewed under
      the premarket notification provisions of the law, but manufacturers have been
      required to provide more extensive safety and effectiveness data to establish
      equivalence to pre-Amendments devices. Data to answer questions related to the
      potential toxicity of breakdown products, period of absorption, and ultimate
      clinical effectiveness needed to be answered prior to marketing. New devices that
      incorporate technologies that are not substantially equivalent to predicate
      devices must proceed through the premarket approval route to marketing. For new
      devices considered a potential significant risk to the patient population,
      clinical trials are conducted via the investigational device exemption (IDE)
      requirements that specify the means by which trials will proceed in order to
      protect the rights of patients. New devices of organic origin, such as bone
      morphogenic protein, have followed the premarket approval route with IDE
      requirements instituted as a condition for their path to the marketplace. Issues
      associated with immediate and long-term contact including potential toxicity,
      tumorigenicity, and sensitization need to be addressed with appropriate animal
      models.

PMID- 9151557
TI  - Outcome variables for the study of periodontal regeneration.
AB  - The most reliable outcome variable for assessing periodontal regeneration is
      human histology; however, the morbidity associated with this technique makes it
      feasible only in isolated case studies designed to prove that a drug, device, or
      technique is capable of regenerating the lost periodontium including bone,
      cementum, and functionally oriented periodontal ligament. In the absence of this
      genuine variable, other "surrogate" variables must be used. Of these, measurement
      of new bone is the primary alternative. Direct bone measurements, including
      linear and volumetric assessment, are by far the best tools; however, the need
      for a second surgical procedure is a definite drawback of this technique. To
      overcome this problem, other outcomes have been employed: sounding bone
      measurements is a less invasive method, albeit it is also less accurate. Another
      tool that has been tested extensively is radiographic analysis. Conventional
      radiography is not useful in most regenerative trails where minimal or no crestal
      changes occur. The use of standardized radiographs and image processing
      techniques to measure alveolar bone changes has not significantly enhanced the
      applicability of this method. Digital subtraction radiography (DSR) offers some
      improvement over previous techniques; however, the correlation between the
      magnitude of clinical bone changes and changes in the digital image is yet to be
      substantiated. Other variables have been successfully used in regenerative
      studies. These include clinical attachment level changes, change in probing
      depth, and gingival recession. The information derived from these variables,
      especially attachment level changes, supplement and substantiate the direct bone
      measurements. Other variables that may be monitored are those associated with
      plaque formation, periodontal pathogens and gingival inflammation; while not
      direct measures of regeneration, these variables are likely to affect future
      prognosis and treatment stability. In summary, direct bone measurements are the
      most ideal surrogate outcome variable, although clinical attachment level
      measurements are commonly used in large-scale regenerative clinical trials.
      Clinical response may be assessed at different time intervals; however, the
      endpoint measurements for regenerative studies should be taken at least 12-months
      postoperatively.

PMID- 9151558
TI  - Specific issues in clinical trials on the use of barrier membranes in periodontal
      regeneration.
AB  - There are presently a number of different barriers available for use clinically
      in guided tissue regeneration (GTR) procedures. A number of trials using these
      techniques and comparing different types of barrier membranes are being published
      in the scientific literature. This review discusses issues related to clinical
      trials on the use of barrier membranes in periodontal regeneration. Outcome
      measures, both clinical and histological, are discussed in relation to results
      following GTR procedures. The difference between regeneration and repair is
      reviewed as well as methods of clinical and histologic assessment of both these
      outcomes. Data regarding the impact of patient variables and tooth or defect
      variables on outcomes are presented and suggestions for study designs are made
      based on these variables. Aspects of assessing for an appropriate sample size in
      superiority and equivalency trials using GTR techniques are presented as well as
      interpretation of results following these trials and their clinical significance.

PMID- 9151559
TI  - The use of biologic response modifiers in human clinical trials.
AB  - To optimize regeneration of the periodontium, new cementum, periodontal ligament,
      and bone must be formed. Conventional periodontal surgery decreases the
      likelihood of continued progressive periodontal disease however, it does not lead
      to significant periodontal regeneration. In vitro studies have identified a class
      of biologic response modifiers loosely referred to as growth factors, which
      stimulate the cellular events of tissue regeneration. The most promising are
      mitogenic and differentiation factors. Based on promising results from animal
      studies, the application of growth factors to predictably stimulate periodontal
      regeneration is entering human clinical trials. This manuscript deals with
      several important considerations in testing biologic response modifiers in
      humans. Suggestions are made regarding the following parameters: 1) selection of
      the unit of measurement; 2) patient and lesion selection; 3) identification of
      controls; 4) selection of outcome parameters; 5) statistical approach; and 6)
      considerations in treatment regimens.

PMID- 9151560
TI  - Overview of clinical trials on endosseous implants.
AB  - Early history of clinical trials on endosseous implants revolved around anecdotal
      reports on predominantly blade implants in the U.S. The first criteria to define
      success or failure were established at the National Institutes of Health (NIH)
      Harvard Conference in 1978. This was followed by the multi-center trials from the
      Branemark group which described round, metallic implants. At the 1988 NIH
      Conference, questions dealt with the following: 1) the effectiveness of dental
      implants for the long-term; 2) indications and contra-indications of various
      types of implants; 3) requirements for management of dental implants; 4) health
      risks of dental implants; and 5) future directions in research. In the ensuing 7
      years since the second NIH Conference, most of the data generated have been from
      non-controlled case reports, which describe a 90% success rate in 5 years or more
      with many types of endosteal systems in both partially and fully edentulous
      patients. Therefore, it can be said that there is evidence that dental implants
      are effective for the long-term. The other questions posed at the 1988 NIH
      Conference have not been as well described and have led to many controversies and
      future research areas. Two areas which will have a special future impact are 1)
      the establishment of a standard of care and risk-benefit ratio for implants and
      2) the use of various factors to accelerate bone formation to allow greater
      access to dental implants by patients.

PMID- 9151561
TI  - The Food and Drug Administration and the regulation of clinical trials for
      endosseous implants.
AB  - The Office of Device Evaluation (ODE), within the Center for Devices and
      Radiological Health of the Food and Drug Administration is the primary component
      responsible for the premarket review of medical devices. Dental devices are
      reviewed by the Dental Devices Branch within ODE. Premarket submissions to FDA
      for dental endosseous implants should include complete characterization of the
      device and often may necessitate the inclusion of mechanical and other bench
      testing and clinical data. FDA guidance documents are available which outline the
      information that should be included in the submissions. The guidance document for
      premarket approval submissions for dental endosseous implants also provides
      guidance on clinical trials for dental implants. This guidance document addresses
      such issues as the number of patients and study sites, length of follow-up, post
      implant assessment, and pooling of data. The review of dental endosseous implants
      involves many challenging issues, including success/failure criteria, new designs
      and new indicated uses. The Dental Branch continues to gather information to
      address these issues.

PMID- 9151562
TI  - Outcomes and their measurement in clinical trials of endosseous oral implants.
AB  - The clinical suitability of an oral implant system should be substantiated by
      well-planned clinical trials that meet the expectations of both the patient and
      the clinician; i.e., to offer anchorage to a dental prosthesis for one or more
      decades. The literature often reports on the survival rather than on the success
      rate, and for the latter a large variety of more or less stringent criteria have
      been proposed. Although the use of cumulative percentages to assess survival or
      success on consecutive patients, the so-called Kaplan-Meier statistics, is
      essential, many publications only report on absolute percentages, thus giving
      much too optimistic results. Indeed, the large number of recently inserted
      implants tend to dilute the small fraction that has gone through the maximum
      observation period. Multi-center studies on consecutive patients who are not
      selected on the basis of bone quality and volume should be recommended. Otherwise
      the labeling of the implant should clearly mention which groups; e.g., smokers or
      patients with limited bone volume are not part of the validated target group. The
      final outcome measurement would be that an endosseous implant is no longer able
      to carry out its purpose: to anchor or support successfully a functional dental
      prosthesis. Like many other clinical evaluations, surrogate parameters have been
      sought to assess interim success rates. The stability of the marginal bone level
      is one parameter proposed by many, although bone loss as such is not synonymous
      with failure. Several implant systems with a roughened surface (plasma sprayed or
      coated) suffer from progressive marginal bone loss and consequently ongoing loss
      of implants even after 5 or more years. Those implant systems should be evaluated
      with cumulative success rates over a period of 10 years. Only those that
      demonstrated a clustering of both bone and implant loss during the first 1 or 2
      years after insertion and subsequently a levelling off for those two parameters-a
      so-called plateau pattern, should be allowed to draw conclusions after 5 years.
      Since radiographs reveal only the approximal areas, measurement of the attachment
      level by means of probing towards a reference point on the abutment should also
      be performed annually. Intra-oral radiographs can only reveal absence of
      radiolucency at the bone-implant interface, but do not prove osseointegration.
      The use of an electronic device offers objective results and reveals even
      subclinical mobilities of endosseous implants. One can conclude that there is an
      urgent need for a consensus between health authorities, third parties, and the
      scientific community to define a set of universally-acceptable success criteria,
      to impose the use of cumulative success rates, and to ask for observation periods
      of 10 years for implants that do not demonstrate stable results after one or two
      years.

PMID- 9151563
TI  - Clinical trials of endosseous implants: issues in analysis and interpretation.
AB  - The majority of contemporary endosseous dental implant systems are based on
      designs and materials that, over the last three decades, have proved to be
      predictably reliable. With proper surgical and prosthetic protocols, rates of
      implant loss have been held to 15% or less over a 5-year period. This information
      was obtained largely through longitudinal descriptive studies, primarily aimed at
      obtaining implant survival rates under ideal clinical conditions, with strict
      inclusion and exclusion criteria for admitting patients into the studies. It is
      important to emphasize that under conditions of routine clinical practice, where
      patient selection may be more relaxed than in clinical trials and clinicians
      attempt to stretch the limits of current technology, the survival rates may not
      necessarily match those reported in the literature. Since "surviving" implants
      may exhibit characteristics likely to lead to eventual loss of the implant, for
      example severe osseous defects, such implants may not necessarily be considered
      successful. Successful implants should fulfill a list of other criteria
      considered essential for long-term survival. Differences in implant design
      preclude some of these criteria from being uniformly applied to all systems.
      There is a need to identify criteria for success that can be applied to the
      majority of implant systems. Implants that fail to meet these criteria should be
      considered failures. Since failure rates may include "failed" as well as
      "failing" ("ailing") implants, the two categories should be listed separately.
      From a practical standpoint, implant failures can be grouped into "early"
      failures, primarily the result of surgical and/or postoperative complications,
      and "late" failures that arise during and following the restorative phase. The
      ability of individual systems to achieve excellent success rates, despite some
      major differences in their design from other systems, suggests that some
      requirements, initially considered essential for success, may not be as critical
      as originally believed. Examples include the need for submerging implants during
      initial wound healing or the need for stress breaking devices. On the other hand,
      a basic requirement for implant success, such as primary stability at the time of
      insertion and following loading of the implant, may be the unifying principle
      behind the need for adequate bone volume and density, longer or wider implants,
      and the 3 to 6-month delay recommended before implants are placed in function.
      With relatively low failure rates, a large number of patients may have to be
      included in long-term clinical trials before a statistically significant
      association can be established between failure rates and potential contributing
      factors. For the same reasons, and to avoid type 2 errors, large populations may
      be needed to show that two systems have comparable success rates. Proving the
      superiority of one system over another may require fewer subjects. Given the
      overall low failure rate and the tendency of failures to cluster in individual
      subjects, failure rates could be markedly affected by the attrition of a few
      critical subjects. Additional research is needed to validate methods in current
      use for the clinical determination of osseointegration, and the diagnosis and
      treatment of occlusal trauma and microbial infections around implants. Also, more
      reliable methods are needed for the identification of the primary cause(s) of
      implant morbidity; i.e., infection or occlusal factors.

PMID- 9151564
TI  - Clinical trials on placement of implants in existing bone.
AB  - The use of dental implants has become a predictable and frequently used treatment
      modality in partially and fully edentulous patients. In 1987, the United States
      Food and Drug Administration (FDA) classified dental implants as class III
      medical devices. In 1989, a proposed rule was published by the FDA calling for a
      Premarket Approval Application (PMA) for dental implants. A PMA requires the
      demonstration of safety and effectiveness through clinical trials. Although the
      effective date for Premarket Approvals and detailed information on study
      requirements have not been announced, many implant manufacturers have already
      initiated multi-center clinical trials. Despite these initiatives, several
      aspects regarding appropriate study designs, outcome criteria, and success or
      failure analysis still need clarification. Trials should be designed to minimize
      bias and variability. The cornerstone of the experimental design is set by the
      study objective. It will determine which of many possible clinical trial
      parameters are essential to enable the presentation of data to a regulatory body
      on which basis the safety and effectiveness of a device can be judged. With the
      multiplicity of patient characteristics, implant types, supported prostheses,
      study designs, evaluation parameters, and statistical analyses, it is a difficult
      task to design an optimal trial. It is the purpose of this paper to propose
      designs and components for implant clinical trials with various objectives.

PMID- 9151565
TI  - Clinical trials on implants in regenerated bone.
AB  - The lack of a sufficient volume of healthy jaw bone was the most important local
      contraindication for the placement of dental implants in the 1980s. Thus, several
      attempts have been made in the past 10 years to develop new surgical methods for
      the reconstruction of lost jaw bone in potential implant patients. At present,
      methods such as guided bone regeneration utilizing barrier membranes or sinus
      lift procedures are widely used in dental offices. There are, however, some
      concerns about the efficacy and predictability of these procedures. There is a
      need to determine how new bone regenerative procedures should be properly
      evaluated. The goal of the present paper is to establish some guidelines for
      clinical trials on implants in regenerated bone. It is proposed that such trials
      should be conducted in two main phases according to predetermined endpoints. The
      first main phase evaluates the new bone regenerative procedure. This almost
      always requires an initial development period including step-by-step
      modifications to identify essential surgical factors for the achievement of
      successful treatment outcomes. At the end, the surgical protocol will be
      established in detail. This is followed by the validation period to evaluate
      efficacy and predictability of this surgical protocol in a clinical study with
      consecutively treated patients. After successful bone regeneration has been
      properly documented, the second main phase evaluates the implants inserted in
      regenerated bone in a prospective clinical study utilizing the same protocol as
      for implants in pristine, non-regenerated bone. This documentation allows the
      evaluation of tissue integration of these implants and their 5-year success
      rates.

PMID- 9151566
TI  - Clinical trials on therapies for peri-implant infections.
AB  - Peri-implant infections are pathological conditions which are normally localized
      in the soft tissues surrounding an oral implant. They may range from a rather
      localized mucositis lesion reflecting the host response to a bacterial challenge
      to a more advanced lesion "termed peri-implantitis" when previously
      osseointegrated oral implants have been partially disintegrated; i.e. have lost
      alveolar bone around the implant. Usually these lesions start as a result of
      plaque accumulation and show similar progression as observed around teeth.
      Muscositis seems to be a prerequisite for the following peri-implantitis.
      However, the factors involving the transition to a more advanced lesion are still
      not known. Logically, the therapy for peri-implant infection has to be related to
      antibacterial treatment prior to the attempt to surgically regenerate peri
      implant alveolar bone lost as a result of the infection. In order to diagnose
      these lesions at an early stage frequent assessments of clinical parameters are
      needed during maintenance therapy. The anti-infective treatment may intercept the
      development of the lesion. Following mechanical debridement of plaque deposits
      the application of efficacious antiseptics (chlorhexidine) is a necessity.
      Following this, antibiotics may cumulatively be applied to control the infection.
      Only a few longitudinal studies have documented the efficacy of such treatment
      regimens, and controls have generally not been available for ethical reasons. In
      regenerating the lost jaw bone only case reports are available today. Controlled
      animal studies will have to be performed to document the possibility of re
      osseointegration and the factors influencing predictability.

PMID- 9151567
TI  - Human gingival fibroblast migration promoted by platelet-derived growth factor on
      titanium is correlated with release of urokinase type plasminogen activator.
AB  - The purpose of this study was to examine if the migration of human gingival
      fibroblasts on titanium was promoted by platelet-derived growth factor (PDGF) and
      whether the release of urokinase-type plasminogen activator (uPA) was correlated
      with it. The migration of the fibroblast on titanium was significantly promoted
      by PDGF in a wound healing assay (p < 0.001). The promotive effect was inhibited
      by aprotinin, a serine protease inhibitor used for the inhibition of uPA (p <
      0.001). The conditioned medium when fibroblast migration was promoted contained a
      higher concentration of uPA than did that of the control. These results indicated
      that the promotive effect of PDGF on the migration of human gingival fibroblasts
      on titanium was correlated with the release of uPA from the fibroblasts.

PMID- 9151568
TI  - Methicillin-resistant Staphylococcus aureus and Candida albicans on denture
      surfaces.
AB  - Infectious diseases caused by methicillin-resistant Staphylococcus aureus, MRSA,
      and Candida albicans are often serious in compromised hosts. We enumerated MRSA
      and C. albicans on denture surfaces and in saliva samples from 29 adults.
      Staphylococcus species, MRSA, and methicillin-resistant Staphylococcus
      epidermidis, MRSE, were detected on 17, 3, and 1 of the 29 denture surfaces,
      respectively. C. albicans were detected on 22 denture surfaces. All saliva
      samples from patients whose dentures carried Staphylococcus species and C.
      albicans were also found to contain both microorganisms. Adherence of isolated 3H
      labeled cells of MRSA and C. albicans to resin beads and saliva-coated resin
      beads was examined. Cells of both microorganisms adhered in significantly higher
      numbers to saliva-coated resin beads than to resin beads. The hydrophobicity of
      the MRSA isolated from denture surfaces varied from strain to strain; that of C.
      albicans strains was moderately high. The zeta potentials of MRSA isolates and of
      C. albicans isolates determined in KCI buffer were significantly low. The
      potential of the resin beads decreased after treatment with saliva. Two out of 5
      MRSA strains were found to be inhibited in growth by oral Streptococcus,
      Actinomyces, and gram-negative bacterial strains, suggesting that some oral
      bacterial species play a role in inhibiting the colonization of Staphylococcus
      species. No isolates of C. albicans were inhibited in their growth by any of the
      oral bacteria tested. Isolates of MRSA and C. albicans coaggregated with
      Porphyromonas gingivalis and Fusobacterium nucleatum strains. Using denture
      cleaners every night for 2 weeks did not reduce numbers of Staphylococcus species
      or C. albicans organisms in saliva.

PMID- 9151569
TI  - Surface reaction between titanium castings and investments.
AB  - The selection of investments suitable for titanium castings is critical because
      the surface-reacted layer greatly affects their mechanical properties. This study
      analyzed the interfacial zone of titanium castings obtained from various
      commercial investments and examined the relationship between the surface-reacted
      layer and the hardness. CP titanium disks (20 mm diameter, 1 mm thick, n = 5)
      were cast using eight commercial casting systems and investments for titanium
      casting: two alumina-based investments (T-invest, CD-titan investment), two
      spinel-based investments (Titanmold, Titavest MZ), three zirconia-based
      investments (Asahivest-D, Titaniumvest EX, Tycast investment TM), and a magnesia
      based investment (Selevest CB). The Vickers hardness of cast disks in cross
      section was tested at 50 microns intervals from the surface to 0.5 mm in depth.
      The cross-section was observed metallurgically, and an elemental mapping
      measurement of the reacted layer was conducted under the EPMA. The Vickers
      hardnesses at 50 microns from the surface of the specimens ranged 312 to 624 and
      were significantly different among the investments (p < 0.01). The thickness of
      the reacted layer, rich in O, Si, Al, Zr, Mg, and P, ranged from 10 to 60
      microns. No correlation was seen between the thickness of reacted layer and the
      hardness (p > 0.05). However, the specimens cast with alumina-based and zirconia
      based investments were harder than the spinel-based and magnesia-based
      investments at 500 microns. Although the free energies of metal oxide formation
      of alumina and zirconia were lower than titania, these data suggest that silica,
      alumina and zirconia were reduced by contact with molten titanium. Accordingly,
      silicon, aluminum and zirconium diffused to the interior of the titanium castings
      and changed their mechanical properties.

PMID- 9151571
TI  - Use of the buccal fat pad as a pedicle graft.
AB  - A technique was developed to use the pedicle buccal fat pad as method for closing
      an oro-antral communication. The buccal fat pad is situated in the posterior part
      of the maxilla and bounded by the pterygopalatine fossa, buccal muscle, and
      masseter muscle. It is supplied by blood from small branches of the maxillary
      artery, the superficial temporal artery, and the facial artery. Generally, the
      buccal fat pad can be easily reached by a horizontal incision over the periosteum
      near the maxillary third molar. As much as 60 x 50mm2 can be obtained. For
      reconstructive surgery, the buccal fat pad is suitable for closing the sinus near
      the hard and soft palate and naso-oral fistulae. In our case, graft tissues after
      surgery healed satisfactorily, began to epithelialize at two weeks after
      operation, and appeared with normal mucous-like changes at about one month. Thus,
      the pedicle buccal fat pad is a safe, simple, convenient, and effective grafting
      method, if it is applied to appropriate cases.

PMID- 9151570
TI  - A morphological study of root resorption of the maxillary first deciduous molars.
AB  - The aim of this study was to elucidate the relationship between root resorption
      of the maxillary first deciduous molars and the developmental state of the
      successive permanent teeth. Twenty-four specimens of the maxilla from 12 dry
      skulls were classified into four dental eruption stages based upon their
      deciduous and permanent dentition. Serial sections prepared from the maxilla and
      embedded in polyester resin were observed with soft X-ray films. The area from
      the lowest point of the protruded part of the zygomatic process to the alveolar
      crest of the maxillary first deciduous molar was divided into 6 areas parallel to
      the Frankfort plane. Specimens from the upper 1/6, 3/6 and 5/6 areas were used.
      In addition, the shortest distance from the root resorption surface to the bony
      crypt was measured. The bony crypt containing the successive permanent tooth germ
      was located closer to the buccal root among the 3 roots of first deciduous molars
      but grew lingually with the progress of eruption stage. The distance from the
      root resorption surface to the bony crypt shortened and resorption actively
      progressed from the deciduous dentition stage to the first molar, and the central
      incisor reached the occlusal line in the deciduous dentition stage. Three
      dimensional reconstruction to reproduce the relationship between the root and
      bony crypt revealed an increase in the root resorption surface with the eruption
      phase and growth of the bony crypt in the direction of root furcation.

PMID- 9151572
TI  - Long-term stability following surgical orthodontic treatment of mandibular
      prognathisms: investigation by means of lateral X-ray cephalogram.
AB  - The purpose of this study was to investigate the long-term stability of jaw
      relations and occlusion following surgical orthodontic treatment of mandibular
      prognathisms and skeletal openbites. Subjects consisted of fifteen adult
      patients. Ten patients underwent the sagittal split ramus osteotomy (SSRO) of the
      mandible and five patients underwent two jaw surgery (Le Fort I osteotomy of the
      maxilla and SSRO of the mandible). They were observed over five years after the
      end of active treatment, and lateral X-ray cephalograms were taken at each stage.
      In the SSRO group, pogonion was retrograded an average of 8.7mm due to the
      operation and it was further replaced 0.4mm backward after the end of active
      treatment. Although the vertical distance between nasion and menton decreased
      2.9mm between the operative period, it increased 1.8mm after the end of active
      treatment. On the other hand, in the two jaw surgery group, point A was advanced
      4.0mm forward and < SNA increased 3.1 degrees between the operative period.
      Pogonion was retrograded 11.4mm between the same period, but moved 0.7mm forward
      after the end of active treatment. A comparison of the osteosynthesis methods
      revealed that pogonion in the wiring group was retrograded 8.3mm backward between
      the operative period, but moved 2.1mm forward during the postsurgical orthodontic
      treatment. Pogonion in the rigid group was retrograded 12.6mm backward between
      the operative period, but moved 1.6mm forward during the postsurgical orthodontic
      treatment. However, both groups were stabilized completely after the end of
      active treatment. A comparison of the differences in the orthodontic treatment
      method revealed that < Ul-SN in the extraction group inclined 8.3 degrees
      lingually during presurgical orthodontic treatment, but it tipped 7.0 degrees
      labially during the postsurgical orthodontic treatment and inclined 3.4 degrees
      lingually after the end of active treatment. < Ul-SN in the non-extraction group
      inclined 5.5 degrees lingually during the presurgical orthodontic treatment, but
      it tipped 2.0 degrees labially during the postsurgical orthodontic treatment and
      inclined 1.9 degrees lingually after the end of active treatment.

PMID- 9151573
TI  - Fundamental study of the relationship between the lateral mandibular position and
      the bulging of the temporal muscle region.
AB  - Greene proposed a temporal-muscle-gripping method to judge the suitability of the
      mandibular position by gripping the temporal muscle region. Ogiwara examined the
      relationship between the anteroposterior mandibular position and the bulging of
      the temporal muscle region. However, the relationship between the lateral
      mandibular position and the bulging of the temporal muscle region has not been
      clarified. In this study, the relationship between the lateral mandibular
      position and the bulging of the temporal muscle region was examined. Five
      dentulous subjects were required to occlude at the tapping point and laterally
      deviated mandibular positions from the tapping point. The bulging of the temporal
      muscle region was measured at each mandibular position. Results were as follows.
      The bulging of the temporal muscle region at occlusion was influenced by lateral
      deviations in the mandibular position. The bulging was larger and started earlier
      on the deviated side than on the opposite side. In the measurement of the
      starting time of bulging of the temporal muscle region, the value of the
      difference in the starting time of bulging between the right and the left side at
      more than 0.4 mm lateral deviated mandibular position was larger than the value
      of the difference in the starting time of bulging between the right and the left
      side at the tapping point in all five subjects (p < 0.05).

PMID- 9151574
TI  - Electrochemical bacteriocidal action based on electron transfer of salivary
      bacteria.
AB  - Based upon the observation that most oral bacteria are negatively charged, we
      attempted to restrain the development of oral bacteria in saliva by applying a
      constant electric potential to an electrode. The development of salivary bacteria
      was clearly restrained by applying 0.74V electric current for 30 min. This
      restraint was in inverse proportion to the concentration of the suspension of
      salivary bacteria. The authors hypothesize that the electrochemical restraining
      was based on electron transfer between the salivary bacteria and the electrode.

PMID- 9151575
TI  - Adenomatoid odontogenic tumor with extensive formation of tubular dentin.
AB  - Although the adenomatoid odontogenic tumor (AOT) is categorized as an odontogenic
      epithelial tumor with odontogenic ectomesenchyme, AOT with induction of true
      tubular dentin with or without concomitant formation of enamel is exceedingly
      rare. This paper reports a case of AOT showing evidence of extensive induction of
      tubular dentin, but without concomitant formation of enamel. The patient was a 20
      year-old female with a rather well-circumscribed intraosseous lesion of the
      maxillary incisor-premolar area without an embedded tooth. Histologically,
      extensive induction of a dysplastic form of tubular dentin with globular
      calcification was evident, in addition to the characteristic histological
      features of AOT. The present case lends support to the categorization of AOT as
      an odontogenic tumor consisting of a disorderly mixture of odontogenic epithelium
      and odontogenic ectomesenchyme with or without dental hard tissue formation.

PMID- 9151576
TI  - New directions for dental education in Japan.
AB  - To meet recent changes in the oral health sciences, general science, and social
      needs, the guidelines for the dental curriculum were revised by the Japanese
      Deans Meeting in 1994. This new program addresses the need to modify both
      undergraduate and postgraduate dental education in Japan. Lifelong education for
      dentists has been also modified recently. Reforming of dental education is pushed
      forward with the concept of continuity and flexibility. In this report, an
      overview of dental education and the most recent dental curriculum in Japan is
      briefly discussed.

PMID- 9151577
TI  - Functioning survival rate of fixtures and superstructures of osseointegrated
      implants: ten years of progress in Tokyo Dental College Hospital (second report).
AB  - Osseointegrated implant bridges (OIB) have shown excellent results in the
      majority of cases. Since 1983, 1,022 fixtures has been applied to 241
      superstructures in Tokyo Dental College Hospital. The aim of present study was to
      examine their functioning survival rate during recent ten years. The functioning
      survival rate of the superstructure of OIB has been almost 100% in both maxilla
      and mandible. Although 13.0% of these fixtures had to be removed in maxillary
      complete cases, only 3.3% of fixtures were removed in other cases. In maxillary
      complete cases, the functioning survival rate of OIB fixtures gradually decreases
      from 91% to 74% (91%, less than 3 years; 84%, between 3 and 7 years; 74%, more
      than 7 years), but it remained at about 97% for all periods in other cases.
      Apparently, the functioning survival rate of OIB fixture is generally determined
      within the period of one year, so almost the same rate is maintained thereafter.
      It is suggested that if more fixture numbers in the superstructure were applied
      to maxillary complete cases, the functional survival rate might improve.

PMID- 9151578
TI  - A study on the tapping point drawing method for registration of maxillomandibular
      relationships in edentulous patients: Part I. Influence of the tapping force on
      the tapping point.
AB  - To investigate the registration of maxillomandibular relationships by the tapping
      point drawing method, the characteristics of tapping points were measured in ten
      edentulous subjects by tracing the tapping points when various tapping forces
      were used. In seven subjects, when tapping involved a heavy force, the tapping
      point position markedly shifted from the position when light force was used. The
      position of the tapping point shifted in the antero-posterior direction in five
      subjects and in the right-left direction in two others. The tapping point
      position of the other three subjects did not change when stronger tapping forces
      were applied; these tapping points either coincided with the apex of the gothic
      arch or included it. Furthermore, in all subjects, the tapping point size
      increased when the degree of tapping force increased. However, the degree of
      increase in tapping point size was smaller in the subjects in whom the tapping
      point position coincided with the apex of the gothic arch or included it. From
      these findings, we have confirmed that accurate tapping point tracing
      necessitates controlling the tapping force.

PMID- 9151579
TI  - Clinical and histological observations of continuously formed bilateral
      mandibular deciduous central incisor roots after traumatic coronal destruction.
AB  - We encountered a rare case of continuously forming bilateral mandibular deciduous
      central incisor roots after traumatic coronal destruction. The patient, 3 year 3
      month old boy, had sustained an external injury which had caused the crowns of
      hist bilateral deciduous central incisors to fall out when he was 12 months old.
      Oral examination revealed two small, hard tissues resembling tooth structures on
      the alveolar ridge in the area of the lost mandibular central incisors. X-ray
      examination revealed them to be deciduous central incisor roots. We observed the
      extracted roots histologically and found that the lesion of the crown fracture
      and pulpal exposure on these roots was completely covered by newly formed
      irregular dentin and cementoid tissues. In this case, the causes of the
      continuous root formation were considered to be that the pulp tissues of
      traumatized teeth were able survive, so the injured lesion was quickly healed and
      covered with gingival tissue. The vital pulp produced the reparative hard tissue,
      sealing the site of pulpal exposure and continuing root formation after the
      trauma.

PMID- 9151580
TI  - Inhibitory effects of funoran on the adherence and colonization of oral bacteria.
AB  - Funoran, a sulfated polysaccharide extracted from the seaweed Gloiopeltis
      furcata, strongly inhibited the adsorption of mutans streptococci to saliva
      coated hydroxyapatite (S-HA) used as an experimental pellicle and strongly
      desorbed cariogenic mutans streptococci pre-adsorbed to S-HA. Colonization
      inhibition and anticariogenic effects of funoran were also investigated in
      experimental rats. The colonization of Streptococcus cricetus E49 inoculated on
      the molar teeth of experimental rats administered funoran was less frequent than
      that in a funoran-free group. The mean buccal and lingual, sulcal, and total
      caries scores of rat groups administered funoran were significantly lower than
      those of the funoran-free group. The inhibitory effect of funoran on
      periodontopathic bacterial attachment was studied in vitro. Funoran strongly
      inhibited the adsorption of Porphyromonas gingivalis, Fusobacterium nucleatum,
      and actinomyces species to S-HA and collagen-coated hydroxyapatite (Co-HA) and
      apparently inhibited their attachment to the human gingival fibroblast Gin-1 cell
      line. The present study indicates that funoran inhibits colonization by
      cariogenic and periodontopathic bacteria and excludes them from human oral
      cavity.

PMID- 9151581
TI  - Properties of the elastic modulus from buccal compact bone of human mandible.
AB  - The aim of this study was to elucidate the elastic modulus of the mandible, which
      is an important factor in analysis of its physical dynamics. To meet this need,
      three point bending tests of small bone specimens were performed. The authors
      concluded that the elastic modulus of the mandible varied with site and
      orientation. When the specimens were obtained from regions paralleling the
      mandibular plane, the values in the lower portions were generally higher than
      those in the upper portions, indicating that these regions are more rigid. The
      elastic modulus in the marginal portions of the mandible, such as the mandibular
      plane, had comparatively high values. Relatively lower values were found as the
      angle to the margin of the mandible increased. In the incisal and premolar
      regions, anisotropic characteristics approximated those of unidirectional fiber
      reinforced composite materials. In the molar regions, there was a broad
      distribution of values, reflecting the complexity of mandibular structure.

PMID- 9151582
TI  - Transposition of the mental nerve and inferior alveolar nerve trunk.
AB  - Transposition of the mental nerve trunk is performed as a preprosthetic
      procedure. It is effective for patients with hyperesthesia caused by dental
      prosthesis and resorption of the alveolar ridge caused by aging. It is also
      performed to protect a location for implant insertion and to preserve the
      inferior alveolar nerve during mandibular tumor excision surgery. The demand for
      this surgery is increasing. The disadvantages of the surgery performed with the
      usual methods include the difficulty of the procedure and the long operation
      time. In an attempt to solve these problems, this study was conducted at the
      Department of Oral and Maxillofacial Surgery, Medical University Hanover,
      introducing an improved surgical method and presenting the actual operation
      performed in our department. This surgical method is considered superior because
      it is easy to perform, requires no special equipment and results in recovery of
      the mental nerve after surgery.

PMID- 9151583
TI  - Microbiology of ligature-induced marginal inflammation around osseointegrated
      implants and ankylosed teeth in cynomolgus monkeys (Macaca fascicularis).
AB  - The microbiota associated with ligature-induced marginal inflammation around
      osseointegrated dental implants, ankylosed teeth, and normal control teeth was
      investigated in 8 cynomolgus monkeys (Macaca fascicularis).
      Submucosal/subgingival plaque was sampled with paper points on the day of
      literature placement and after 7 weeks. The samples were evaluated by phase
      contrast microscopy and by cultivation on enriched non-selective and various
      solid media. The submucosal/subgingival flora was changed 7 weeks after ligation.
      The total number of cultivable bacteria and the proportions of motile rods,
      anaerobic Gram-negative rods, black-pigmented rods, Porphyromonas gingivalis, and
      Prevotella intermedia increased significantly around implants, ankylosed teeth,
      and normal control teeth. Except for a significantly higher proportion of
      anaerobic Gram-positive cocci around implants compared to ankylosed teeth and
      normal control teeth at the end of the study, no significant microbiological
      differences were observed between implants, ankylosed teeth, and normal control
      teeth neither at baseline nor at the end of the study. Consequently, the
      microbiota associated with marginal inflammation around implants, ankylosed
      teeth, and normal control teeth appears to be rather similar in cynomolgus
      monkeys.

PMID- 9151584
TI  - The influence of abutment surface roughness on plaque accumulation and peri
      implant mucositis.
AB  - Bacterial adhesion to intra-oral, hard surfaces is firmly influenced by the
      surface roughness to these structures. Previous studies showed a remarkable
      higher subgingival bacterial load on rough surfaces when compared to smooth
      sites. More recently, the additional effect of a further smoothening of intra
      oral hard surfaces on clinical and microbiological parameters was examined in a
      short-term experiment. The results indicated that a reduction in surface
      roughness below R(a) = 0.2 microns, the so-called "thresholds R(a)", had no
      further effect on the quantitative/qualitative microbiological adhesion or
      colonisation, neither supra- nor subgingivally. This study aims to examine the
      long-term effects of smoothening intra-oral hard transgingival surfaces. In 6
      patients expecting an overdenture in the lower jaw, supported by endosseus
      titanium implants, 2 different abutments (transmucosal part of the implant): a
      standard machined titanium (R(a) = 0.2 microns) and one highly polished and made
      of a ceramic material (R(a) = 0.06 microns) were randomly installed. After 3
      months of intra-oral exposure, supra- and subgingival plaque samples from both
      abutments were compared with each other by means of differential phase-contrast
      microscopy (DPCM). Clinical periodontal parameters (probing depth, gingival
      recession, bleeding upon probing and Periotest-value) were recorded around each
      abutment. After 12 months, the supra- and subgingival samples were additionally
      cultured in aerobic, CO2-enriched and anaerobic conditions. The same clinical
      parameters as at the 3-month interval were recorded after 12 months. At 3 months,
      spirochetes and motile organisms were only detected subgingivally around the
      titanium abutments. After 12 months, however, both abutment-types harboured equal
      proportions of spirochetes and motile organisms, both supra- and subgingivally.
      The microbial culturing (month 12) failed to detect large inter-abutment
      differences. The differences in number of colony- forming units (aerobic and
      anaerobic) were within one division of a logarithmic scale. The aerobic culture
      data showed a higher proportion of Gram-negative organisms in the subgingival
      flora of the rougher abutments. From the group of potentially "pathogenic"
      bacteria, only Prevotella intermedia and Fusobacterium nucleatum were detected
      for anaerobic culturing and again the inter-abutment differences were negligible.
      Clinically, the smoothest abutment showed a slightly higher increase in probing
      depth between months 3 and 12, and more bleeding on probing. The present results
      confirm the findings of our previous short-term study, indicating that a further
      reduction of the surface roughness, below a certain "threshold R(a)" (0.2
      microns), has no major impact on the supra- and subgingival microbial
      composition.

PMID- 9151585
TI  - The peri-implant hard and soft tissues at different implant systems. A
      comparative study in the dog.
AB  - The aim of this study of the present experiment was to study the marginal
      periimplant tissues at intentionally non-submerged (1-stage implants) and
      initially submerged and subsequently exposed implants (2-stage implants). 5
      beagle dogs, about 1-year-old, were used, 3 months after the extraction of the
      mandibular premolars, fixtures of the Astra Tech Implants Dental System, the
      Branemark System and the Bonefit--ITI system were installed. In each mandibular
      quadrant, 1 fixture of each implant system was installed in a randomised order.
      The installation procedure followed the recommendations given in the manuals for
      each system. Thus, following installation, the bone crest coincided with the
      fixture margin of the Astra Tech Implants Dental System and the Branemark System,
      whereas the border between the plasma sprayed and the machined surface of the
      Bonefit-ITI implant system was positioned at the level of the bone crest.
      Following a healing period of 3 months, abutment connection was carried out in
      the 2-stage systems (the Astra Tech Implants Dental System and the Branemark
      system). A 6-month period of plaque control was initiated. The animals were
      sacrificed and biopsies representing each important region dissected. The tissue
      samples were prepared for light microscopy and exposed to histometric and
      morphometric measurements. The mucosal barrier which formed to the titanium
      surface following 1-stage and 2-stage implant installations comprised an
      epithelial and a connective tissue component, which for that 3 systems studied,
      had similar dimensions and composition. The amount of lamellar bone contained in
      the periimplant region close to the fixture part of the 3-implant systems was
      almost identical. It is suggested that correctly performed implant installation
      may ensure proper conditions for both and hard tissue healing, and that the
      geometry of the titanium implant seems to be of limited importance.

PMID- 9151586
TI  - Rehabilitation of mandibular edentulism by single crystal sapphire implants and
      overdentures: 3-12 year results in 86 patients. A dual center international
      study.
AB  - 86 patients, in 2 Scandinavian centers, participated in a prospective study of
      mandibular edentulism, treated with overdentures supported by Bioceram sapphire
      implants. Implant success and prosthesis stability as well as parameters for peri
      implant health were evaluated. Masticatory function and complications were also
      documented. The study began in 1991 and clinical treatment of the last patients
      was completed in 1991. The patients have been followed for at least 3 years, and
      up to 12 years. 4 patients were lost to follow-up. Of the initial 324 implants, 7
      implants failed before prosthetic treatment. 3 patients lost 1 implant each
      within the 1st year, and 4 patients lost all 4 implants. 16 implants were lost
      between 36 and 42 months in function, due to lack of osseointegration and pain.
      The loss of implants could be attributable to an association, not statistically
      verified, between bone quality and anatomy, with heavy smoking as a risk factor.
      Based on the remaining implants, the cumulative implant success rates were 95.2%,
      91.3%, 91.3%, 91.3% at 3, 5, 10 and 12 year follow-up respectively. The
      cumulative success rates for overdentures were 96.4%, 92.8% and 92.8%
      respectively, for the same follow-up periods. Indices for the health of the peri
      implant mucosa disclosed no serious inflammatory reactions in the surrounding
      soft tissues. Patient satisfaction with this form of oral rehabilitation was high
      in all but 2 patients who experienced discomfort.

PMID- 9151587
TI  - Correlations between radiographic, clinical and mobility parameters after loading
      of oral implants with fixed partial dentures. A 2-year longitudinal study.
AB  - The aim of present study was to correlate the changes in the peri-implant tissues
      occurring after functional loading of non-submerged titanium implants and
      assessed by radiographic, clinical and mobility measurements. 11 patients with
      distal extension situations received 18 implants of the ITI Dental Implant
      System. After a healing period of 3 months, the suprastructures were fabricated
      and seated 5 months post-surgically. For the assessment of peri-implant bone
      changes, standardized vertical bitewing radiographs with reproducible exposure
      geometry were evaluated using computer assisted densitometric image analyses
      (CADIA) and bone height measurements. Since the radiographic evaluations were
      performed at mesial and distal sites only, the clinical parameters from these
      implant aspects were included in the analysis. Clinical periodontal parameters
      modified for the use around implants were obtained, damping characteristics were
      expressed as Periotest readings and standardized radiographs were obtained at 1,
      3, 6, 12 and 24 months after loading. In addition, radiographs were also taken at
      the start of functional loading. The data obtained from this small sample of
      implants demonstrated a wide range of different tissue alterations when using
      radiographic, clinical and mobility assessments. The parameters of probing
      attachment level (PAL) in combination with radiographic parameters obtained at 1,
      3, and 6 months after loading were good predictors for the peri-implant tissue
      status at 2 years. This was shown by means of multiple stepwise regression
      analyses. Mobility measurements did not reveal valuable predictive information
      with the statistical models applied. Assessments of probing attachment levels
      using periodontal probes rendered information on peri-implant tissue alterations,
      which were closely correlated to the radiographically measurable peri-implant
      bone changes.

PMID- 9151588
TI  - Evaluation of an endosseous titanium implant with a sandblasted and acid-etched
      surface in the canine mandible: radiographic results.
AB  - Previous studies have demonstrated in short-term experiments that sandblasted and
      acid-etched (SLA) titanium implant had a greater bone-to-implant contact than a
      titanium plasma-sprayed (TPS) implant in non-oral bone. In the present study, an
      SLA implant was compared radiographically to a TPS implant under unloaded and
      loaded conditions in the canine mandible for up to 15 months. 69 implants were
      placed in 6 foxhounds. Standardized radiographs were taken at baseline, preload,
      3, 6, 9, and 12 months of loading. Loaded implants were restored with gold crowns
      similar to the natural dentition. Radiographic assessment of the bone response to
      the implants was carried out by measuring the distance between the implant
      shoulder and the most coronal bone-to-implant contact (DIB) and by evaluated of
      bone density changes using computer-assisted densitometric image analysis
      (CADIA). 5 different areas-of-interest (AOI) were defined coronally and apically
      along the implant. DIB measurements revealed that SLA implants had significantly
      less bone height loss (0.52 mm) than TPS implants (0.69 mm) at the preload
      evaluation (p = 0.0142) as well as at 3 months of loading (0.73 mm/1.06 mm; p =
      0.0337). This difference was maintained between the implant types during the 1
      year follow-up period. The same trend was also evident for CADIA measurements
      with SLA implants showing higher crestal bone density values when comparing
      preload to baseline data (p = 0.0890) and 3 months to baseline data (p = 0.0912).
      No measurable bone density changes were apparent in the apical areas of either
      implant. These results suggest that SLA implants are superior to TPS implants as
      measured radiographically in oral bone under unloaded and loaded conditions.

PMID- 9151590
TI  - Quantitative determination of the stability of the implant-tissue interface using
      resonance frequency analysis.
AB  - Bone anchored implants are now being used in dentistry for supporting intraoral
      and craniofacial prostheses. Although high success rates have been reported, a
      small number of implants may fail during the early healing phase or lateral in
      function. Currently available clinical methods to determine implant stability and
      osseointegration are relatively crude and may entail percussing a fixture with a
      blunt instrument. Radiographs are of value, but a standardised technique is
      necessary to ensure repeatability. This investigation was designed to study the
      application of a non-invasive test method using resonance frequency analysis to
      make quantitative measurements of the stability of the implant tissue interface
      in-vitro and in-vivo. The resonance frequency of a small transducer was measured
      when attached to implants embedded at different heights in an aluminum block. A
      strong correlation (r = 0.94, p < 0.01) was observed between the observed
      frequency and the height of implantation fixture exposed. The change in stiffness
      observed in the bone surrounding an implant during healing was modelled by
      embedding implants in self-curing polymethylmethacrylate and measuring the
      resonance frequency at periods during polymerisation. A significant increase in
      resonance frequency was observed related to the increase in stiffness. Resonance
      frequency measurements were also made on implants in-vivo and the results
      correlated well with the in-vitro findings.

PMID- 9151589
TI  - Procollagen alpha 1(I) transcripts in cells near the interface of coralline
      implants in rats, detected by in situ hybridization.
AB  - Cells procollagen alpha 1(I) transcripts were demonstrated at the interface of
      natural coral mineral implanted in the femur of rats after 7, 14, 21 and 28 days
      by in situ hybridization with digoxigenin-labelled RNA probes. Procollagen alpha
      1(I) transcripts were detectable in osteoblasts between 7 and 28 days after
      implantation. As early as 7 days after implantation, procollagen alpha 1(I) RNA
      expression was also demonstrated in fibroblasts; the transcripts steady state
      levels decreased until the 28th day, when they subsided completely. The
      development of bone was significantly during the 4 weeks of implantation.
      Inhibition of bone development by the coralline material could not be recorded.

PMID- 9151591
TI  - Immediate transmucosal implants using the principle of guided tissue regeneration
      (II). A cross-sectional study comparing the clinical outcome 1 year after
      immediate to standard implant placement.
AB  - The aim of the present study was to compare the peri-implant mucosal conditions 1
      year after immediate transmucosal implant placement without or in combination
      with guided tissue regeneration with the situation after regular placement of
      transmucosal 1-stage procedure implants in partially edentulous patients. The
      test group consisted of 15 patients who required the immediate replacement of 20
      teeth with oral implants in combination with guided tissue regeneration. The
      control group 1 consisted of 6 patients who received 8 immediate implants,
      without concomitant bone regeneration procedure due to the small size of the
      extracted roots in comparison with diameter of the implants. The 20 patients of
      the control group 2 were randomly chosen from over 150 partially edentulous
      patients who received implants of the ITI Dental Implant System according to the
      standard procedure. Similar favorable clinical parameters were found around the
      implants of all the 3 groups with low plaque and mucosal indices, similar amounts
      of recession, pocket probing depths and clinical attachment levels. The immediate
      implants demonstrated lower frequencies of sites bleeding on probing. The study
      has established that immediate oral implants are a feasible treatment modality
      with high predictability.

PMID- 9151592
TI  - Bone regeneration in extraction sites after immediate placement of an e-PTFE
      membrane with or without a biomaterial. A report on 12 consecutive cases.
AB  - The efficacy in restoring a buccal dehiscence after tooth extraction has been
      studied in 12 consecutive cases using guided bone regeneration with (6 patients)
      or without (6 patients) a biomaterial (DFDBA or Bio Oss) beneath an e-PTFE
      membrane. A correlation between the clinical impression of density at drilling
      time and the histological signs of bone formation has been evaluated too. The
      membrane was removed after 6 or 9 months and a biopsy was performed. Clinically,
      GBR was highly predictable for regeneration of the alveolar bone after tooth
      extraction with buccal dehiscence. The histology fully confirmed the clinical and
      radiographical results, showing bone formation in all cases with individual
      variations in the amount of bone formed. 6-month biopsies from the membrane sites
      had lamellar bone with large medullary spaces, while a good bone density was
      observed at 9 months. The membrane/biomaterial sites demonstrated mineralization
      and large amounts of allograft at 6 months. Thus, bone regeneration seems to take
      more time when grafting material is used.

PMID- 9151594
TI  - Transversal fixation of restorations in combination with the Octa abutment of the
      ITI Dental Implant System.
AB  - In aesthetically demanding locations of the dentition, the replacement of a
      single tooth by means of an oral implant is often difficult because of technical
      limitations of the abutments systems used. The transversal Fixation System in
      combination with the Octa abutment of the ITI Dental Implant System presents a
      novel development to overcome these limitations. The report describes the
      engineering and design of this technical development.

PMID- 9151593
TI  - Reconstruction of the resorbed edentulous maxilla using autogenous rib grafts and
      osseointegrated implants.
AB  - 14 patients with severely resorbed edentulous maxillae underwent reconstruction
      by the use of autogenous rib graft on-lays and osseointegrated Branemark System
      implants in a one-stage procedure. 75 implants were installed. 16 (21.3%) failed
      to osseointegrate at the abutment connection. After a mean observation period of
      5.2 years, 55 (73.3%) of the original implants were osseointegrated. 10
      supplementary implants were inserted in 3 patients. At the end of the observation
      periods, 2 patients had overdentures and 12 had fixed prostheses. The mean
      marginal bone loss was 2.13 mm (SD 0.47 mm) the 1st year after grafting, and 2.92
      mm (SD 1.27 mm) at the end of the follow-up periods. Long-term follow-up did not
      show any persistent donor site discomfort. The results indicate that this
      technique is a conceivable alternative for patients with severe maxillary
      resorption.

PMID- 9151595
TI  - Recession of the soft tissue margin at oral implants. A 2-year longitudinal
      prospective study.
AB  - The aim of this study was to longitudinally evaluate alterations in the position
      of the periimplant soft tissue margin, occurring during a 2-year period after
      insertion of fixed prostheses. 41 patients, subjected to treatment with partial
      or full-arch implant supported fixed prostheses based on a total of 163 standard
      Branemark oral implants, were included in the study. A baseline examination was
      performed at time of insertion of the prosthetic construction and involved
      assessments of plaque, mucositis, probing depth, bleeding on probing marginal
      soft tissue level, width of masticatory mucosa and marginal soft tissue mobility.
      All patients were re-examined after 6 months, and after 1 and 2 years,
      respectively. A regression analysis was performed to evaluate if alterations,
      occurring in the position of the periimplant soft tissue margin during the 2
      years, could be predicted by various variables recorded at time of the
      installation of the fixed prosthesis. The descriptive analysis showed a slight
      decrease in mean probing depth (0.2 mm) and width of masticatory mucosa (0.3 mm)
      during the follow-up period. Apical displacement of the soft tissue margin mainly
      took place during the first 6 months of observation. Lingual sites in the
      mandible showed the most pronounced soft tissue recession, decrease of probing
      depth, and decrease of width of masticatory mucosa. The statistical analysis
      revealed that lack of masticatory mucosa and mobility of the periimplant soft
      tissue at time of bridge installation were poor predictors of soft tissue
      recession occurring during the 2 years of follow-up, but indicated in greater
      amount of recession in women than men, in the mandible than in the maxilla, at
      lingual than at facial sites and with increased initial probing depth. It was
      suggested that the recession of the periimplant soft tissue margin mainly may be
      the result of a remodelling of the soft tissue in order to establish "appropriate
      biological dimensions" of the periimplant soft tissue barrier, i.e., the required
      dimension of epithelial-connective tissue attachment in relation to the
      faciolingual thickness of the supracrestal soft tissue.

PMID- 9151596
TI  - Initial attachment of human gingival fibroblast-like cells in vitro to titanium
      surfaces pretreated with saliva and serum.
AB  - Wound healing at the implant-soft tissue interface occurs in the presence of
      saliva and blood. The aim of this in vitro study was to investigate potential
      influence of saliva and serum on initial attachment of human gingival fibroblast
      like cells to titanium (Ti) surfaces 10 x 10 mm large specimens were prepared
      from pure Ti, incubated for 1 h in either whole human saliva, fetal calf serum,
      their mixtures in proportions 75:25, 50:50 and 25:75, or buffer as control.
      Subsequently suspensions of human gingival fibroblast-like cells were applied in
      4 separate assays to Ti surfaces for 40 min and cell attachment was evaluated by
      means of image analysis under reflected light microscopy. Significantly lower
      numbers of attached cells (p < 0.001) were found on all surfaces pretreated with
      saliva alone or in combination with serum. Pretreatment with serum alone showed
      no consistent enhancing effect on cell adhesion. These results suggest that
      exposure of implant necks to saliva during implant insertion or periimplantitis
      treatment might inhibit adhesion of gingival fibroblasts and thus indirectly
      support isolation of the implant by epithelial proliferation.

PMID- 9151597
TI  - Surgical correction of malpositioned implants. A case report.
AB  - A new technique for surgical correction of malpositioned implants is described. A
      64-year-old female got her first fixed prosthesis anchored to 6 Branemark
      implants in her upper jaw, in April 1993. The implants were poorly positioned and
      despite great efforts to make the construction aesthetically acceptable, the
      patient did not approve. In order to obtain better aesthetics, it was decided to
      move some of the osseointegrated implants to other positions. With a trephine
      drill, fixtures were removed including the surrounding bone, and 2 of them were
      placed in new sites made with the same drill. After a healing period of 6 months,
      abutments were connected and a new fixed prosthesis was made. After 1 year of
      loading, all implants were still stable. A marginal bone resorption to the 3rd
      thread was found around one of the implants.

PMID- 9151598
TI  - The effect of antimicrobial therapy on periimplantitis lesions. An experimental
      study in the dog.
AB  - The objective of the present study was to evaluate the effect of systemic
      antibiotics and local debridement in the treatment of experimentally induced
      periimplantitis lesions. 5 Labrador dogs, and about 1-year old, were included in
      the study. In order to establish bilateral recipient sites for implants the
      mandibular right and left 1st molars, 4th and 3rd premolars were removed. 6
      titanium fixtures (Branemark System Nobelpharma AB, Goteborg, Sweden) were
      installed and standard abutments were connected 3 months after fixture
      installation. Cotton floss ligatures were placed in a submarginal position around
      the neck of the abutments and the animals were placed on a diet which allowed
      plaque accumulation. After 6-8 weeks, when the tissue destruction amounted to
      about 20% of the fixture length, the ligatures were removed. 1 month after
      ligature removal, an antibiotic regimen (amoxicillin and metronidazole) was
      initiated and maintained for 3 weeks. In the left side of the mandible, buccal
      and lingual mucoperiosteal flaps were elevated, the granulation tissue within the
      bone craters adjacent to the implants was curetted, and the abutments were
      removed. The exposed outer surface, the internal part of the fixtures, as well as
      the abutments were treated with a detergent, delmopinol. The cleaned abutments
      were autoclaved, and connected to the clean fixtures. The mucoperiosteal flaps
      were replaced to their original position, adapted to the abutments and sutured. A
      careful plaque control program was initiated for the left jaw quadrants. In the
      right side of the mandible no local treatment was given to the fixtures and the
      abutments following ligature removal. Furthermore, no plaque control was provided
      to the implant segments in the right jaws. After 4 months of healing block
      biopsies including one implant with adjacent hard and soft tissue were harvested
      and prepared for light microscopy. It was observed that systemic antimicrobial
      therapy, combined with implant cleaning, curettage of the bone defect and regular
      plaque control resulted in (i) resolution of the periimplantitis lesion, (ii) a
      significant recession of the marginal periimplant mucosa, and (iii) a minor
      additional apical shift of the base of the bone defect. In the untreated sites
      the plaque associated infiltrate remained and was in several sites examined in
      contact with the adjacent bone tissue.

PMID- 9151599
TI  - A prospective 15-year follow-up study of mandibular fixed prostheses supported by
      osseointegrated implants. Clinical results and marginal bone loss.
AB  - In this prospective study 47 edentulous patients were treated with mandibular
      fixed prostheses supported by osseointegrated Branemark implants and followed for
      12 to 15 years. Three (1%) of the 273 inserted implants were lost, two before and
      one six years after placement of the fixed prosthesis. The cumulative success
      rate (CSR) of the implants was 98.9% both after 10 and 15 years. None of the
      fixed prostheses was lost and at the last follow-up, all patients had stable
      fixed prostheses in function (CSR 100%). The marginal bone loss around the
      implants was small, on average 0.5 mm during the first post surgical year and
      thereafter about 0.05 mm annually. More bone was lost around the anterior
      implants than around the most posterior ones. Smoking and poor oral hygiene had
      significant influence on bone loss, while occlusal loading factors such as
      maximal bite force, tooth clenching and length of cantilevers were of minor
      importance. It is concluded that the long-term results of the mandibular implant
      treatment were extremely successful, regarding both the fixed prostheses and
      implant stability. Bone resorption around the implants, albeit limited, was
      influenced by several factors, smoking and oral hygiene appeared to be most
      important.

PMID- 9151600
TI  - Non-submerged implants in the treatment of the edentulous lower jar. A 2-year
      longitudinal study.
AB  - Non-submerged ITI Bonefit implants (ITI Dental Implant System) were inserted in
      edentulous lower jaws of 46 patients. The patients were provided with either a
      fixed prosthesis or an overdenture, and has been followed during a 2-year-period.
      At the 1-year examination, the suprastructures were removed permitting test of
      the individual implant stability. Radiographic examinations were performed in
      connection with the loading of the implants and at the 1-year examination. In
      total 216 implants were inserted. 4 implants were lost before loading and 4
      during the 2nd year of function, which gives a survival rate after 1 year 98% and
      after 2 years of 96%. The mean marginal bone loss during the first year of
      function was 0.1 mm. However, the marginal bone changes had a high degree of
      variation and four implants showed a severe bone loss. The intention is to follow
      this patient group with annual examinations during 5 years.

PMID- 9151601
TI  - A clinical retrospective evaluation of FA/HA coated (Biocomp) dental implants.
      Results after 1 year.
AB  - In this retrospective clinical evaluation, the performance of loaded titanium
      implants with a bilayer bioactive surface coating of the relatively reactive
      hydroxylapatite (HA, outer layer) and the more stable fluorapatite (FA, inner
      layer) was evaluated. 98 consecutive patients were included in the study for a
      total of 354 implants, loaded by overdentures, fixed partial dentures and single
      tooth replacements. Statistical analyses revealed a cumulative probability of
      implant survival on a per patient basis of 94.5% (s.e. 2.7%), one year after
      implant installation. On implants that were lost parts of the bilayer FA/HA
      coating had vanished as a result of primary or secondary infection and
      subsequently epithelial down growth. Most complications were associated with
      implants placed in the maxilla. Periotest values (PTV) were generally high,
      indicating adequate osseointegration. The PTV's were statistically significantly
      less favorable in implants placed in the maxilla. The most favorable PTV's and
      gingival index scores were found around implants servicing overdentures. Marginal
      bone loss averaged approximately 2mm during the observation period. The amount of
      marginal bone loss corresponded with the distance from the neck of the implant to
      the first thread of the implant's cervical screw-section. It is concluded that,
      during the relatively short observation period, the FA/HA coated implants
      function adequately. However, in the absence of a direct implant-to-bone contact
      preceding implant loss, part of the FA/HA coating on the titanium implants
      generally dissolves.

PMID- 9151602
TI  - Radiographic evaluation of mandibular posterior implant sites: correlation
      between panoramic and tomographic determinations.
AB  - The purpose of the present study was to compare bone height determinations of
      implant sites by different radiographic techniques. Available bone height was
      measured in regions posterior to the mental foramen on panoramic radiographs, and
      on tomographs where the faciolingual dimension was at least 5mm. The bone heights
      were recorded at 401 edentulous and dentate sites in 100 patients. The overall
      mean bone height (m +/- SD) was 11.25 +/- 3.29 mm on panoramic radiographs and
      8.81 +/- 3.38 mm on tomographs. The correlation between the two radiographic
      techniques ranged from 0.36 to 0.91 if the material was stratified according to
      factors such as height of available bone, age, gender and the presence of teeth.
      Gender was significantly correlated to panoramic and tomographic measurements in
      all regions. However, the precision of predicted tomographic measurements by
      using a linear regression model was not significantly increased by including
      gender as an explanatory variable. For evaluation of available bone height in
      mandibular regions posterior to the mental foramen, tomography is recommended for
      all prospective implant sites.

PMID- 9151603
TI  - Supracrestal bone growth around partially inserted titanium implants in dogs. A
      pilot study.
AB  - 8 titanium implants (Nobel Biocare, Goteborg, Sweden) were inserted into
      edentulous lower premolar areas of 4 dogs so that 6 threads of the implant
      protruded from the bone crest. Newly-developed perforated dome-shaped titanium
      space maintainers were fixed to the implant with cover screws. Autogenous bone
      fragments were placed under the space maintainers. On one side of the arch, the
      space maintainer was covered with a non resorbable cell occluding barrier. The
      implant/space maintainers were submerged under coronally positioned flaps.
      Following a 3-month healing period, there was a mean gain of new bone amounting
      to 2.5 mm for all specimens. A greater height of bone was found for those sites
      in which an ePTFE membrane was used; 3.1 mm vs. 1.9 mm (p < 0.05). This study
      demonstrated the potential of coronal bone growth of the alveolar bone in a
      protected space around crew implants with exposed treads when placed in the dog.

PMID- 9151604
TI  - Guided bone regeneration in the treatment of periimplantitis.
AB  - The objective of the present experiment was to study the soft and hard tissue
      healing following treatment of experimentally induced periimplantitis. 5 labrador
      dogs about 1-year old were used. The mandibular right and left 1st molars, 4th
      and 3rd premolars were removed, titanium fixtures (Branemark System) were
      installed, and standard abutments were connected in a 2nd stage procedure. After
      3 months experimental periimplantitis was induced by the placement of cotton
      floss ligatures in a submarginal position. 6 weeks later the ligatures were
      removed. 1 month after ligature removal, an antibiotic regimen was initiated.
      During a 3-week period, each dog was given tablets of amoxicillin and
      metronidazole. In the left side of the mandible, buccal and lingual
      mucoperiosteal flaps were elevated and granulation tissue within the bone craters
      curetted. The abutments were removed. The exposed outer surfaces and the internal
      part of the fixtures were carefully cleaned with a detergent (delmopinol HC1). An
      e-PTFE membrane was placed over each fixture and adjusted to cover the bone
      crater. New cover screws were fitted through the membranes to the cleaned
      fixtures. The implants were submerged and the flaps sutured. In the right side of
      the mandible no local treatment was performed. The dogs were sacrificed after 4
      months and biopsies prepared for histological examination. The findings indicated
      that treatment of a periimplantitis lesion, including comprehensive systemic
      antimicrobial therapy and cleaning of submerged implants resulted in (i) the
      elimination of the inflammatory process in the periimplant tissues and (ii) the
      establishment of a dense connective tissue capsule in direct contact with the
      previously exposed surface of the implant system. It was also observed that (iii)
      new bone was frequently laid down on the pristine cover screws.

PMID- 9151605
TI  - Immunological responses to maxillary on-lay allogeneic bone grafts.
AB  - 4 patients with severely resorbed maxillae underwent rehabilitation with on-lays
      of allogeneic femoral head bone grafts, titanium implants (Branemark System) and
      fixed prostheses. Donors and recipients were matched according to blood groups
      (ABO/Rh). Potential immunological responses were monitored by determining
      autoantibodies in peripheral blood, and inflammatory reactions in the recipient
      site. Biopsies from the bone graft 6 months after grafting showed vital bone.
      After a mean observation period of 19.5 months, 22 of 23 implants were
      osseointegrated. None of the investigated autoantibodies were detected in
      peripheral blood, and there was no local inflammatory response. Allogeneic bone
      grafts in combination with titanium implants can be used in reconstruction of
      edentulous severely resorbed maxillae without immunological reactions directed
      against the graft.

PMID- 9151606
TI  - Simultaneous force measurements in 3 dimensions on oral endosseous implants in
      vitro and in vivo. A methodological study.
AB  - A novel piezo-electric force transducer was developed that is mounted directly on
      ITI-implants and allows for simultaneous force measurements in 3 dimensions. The
      reliability of this measuring method in vitro and in vivo was evaluated. For test
      and calibration measurements 5 edentulous patients with 2 mandibular implants
      were selected and master casts obtained with original implants in situ. Preload
      of the abutment screw was measured with a torque controller by repeated
      tightening and loosening. The introduction of additional preloads when bar
      connectors or telescopes were mounted was examined on the casts and in the mouth.
      Tests were carried out to identify the influence of screw tensions on force
      measurements by loading the implants in vertical and transverse directions.
      Calibration measurements in vivo and in vitro were carried out by means of a
      spring balance. A regression model was calculated to analyze the influence of the
      applied preload on measured forces. The mean preload value was 315, ranging from
      200 to 480N. A significant correlation of applied loads to measured forces was
      found (r = 0.99). It was independent of the preload in vertical direction but
      dependent in transverse direction. No additional tension of the abutment screw
      was ever observed when bars were mounted. Calibration measurements with the
      spring balance showed that bars contribute to load sharing between the implants.
      Comparable results were found for all measurements in vitro and in vivo. It was
      concluded that the new piezo-electric transducer is an adequate instrument to
      measure forces in 3 dimensions on ITI-implants.

PMID- 9151607
TI  - 3-D in vivo force measurements on mandibular implants supporting overdentures. A
      comparative study.
AB  - Force transmission onto implants supporting overdentures was measured in vivo by
      means of piezoelectric transducers that allow for simultaneous force
      registrations in 3 dimensions. The transducers are directly mounted onto the
      implants, beneath the anchorage device. The force registrations were analyzed
      with regard to the anchorage device and retention mechanism of overdenture
      support. The 3 types of denture anchorage were a U-shaped bar, a round clip-bar
      and single telescopes. Forces were measured in the following test situations:
      maximum force when biting in centric occlusion, maximum bite force during biting
      on a bite plate, grinding and chewing bread. Multiple regression showed that the
      vertical component of maximum forces was dependent on the anchorage device and
      test situation. The transverse components reached 10 to 50% of the vertical force
      magnitude. With the bite plate in situ maximum forces measured in vertical
      direction were significantly higher or the ipsilateral implant with telescopes
      than with bars (p < 0.01 and p < 0.001). Chewing and grinding resulted in lower
      vertical forces compared to maximum biting. In transverse dimensions, mainly in
      the anterior-posterior direction, registered forces reached magnitudes that
      resembled the vertical component (50 to 100%). Force magnitudes of chewing and
      grinding were similar for all three anchorage devices. However, differences were
      observed between bars and telescopes with regard to the direction of transverse
      force components. The results of this study do not suggest the preference of one
      specific anchorage system or retention mechanism for overdenture support.
      However, rigid bars contribute to load sharing and stress distribution onto the
      implants.

PMID- 9151608
TI  - A pilot study comparing screw-shaped implants. Surface analysis and histologic
      evaluation of bone healing.
AB  - The purpose of this study was to compare surface treatment and bone formation
      adjacent to 2 screw shaped implants of similar design manufactured by two
      different companies. The test implants were manufactured by SERF (Decines,
      France), while the controls were manufactured by Nobelpharma (Goteborg, Sweden).
      The surface of 3 standard 3.75 mm test and 3 standard 3.75 mm control implants
      were investigated by means of scanning electron microscopy (SEM), X-ray micro
      analysis, electron spectroscopy for chemical analysis (ESCA) and surface
      topography analysis. There was a microscopic difference on the thread design
      (SEM). Test threads were flat at the edge, while controls appeared rounded at the
      edge of the threads. Tests and controls were made of commercially pure titanium,
      with a regular topography. Results of ESCA indicated that the carbon peak for
      SERF implants was slightly higher than for the Branemark implants. 5 test and 5
      control implants were installed into the epiphyseal head of the femur of 2 ewes
      using a standardized surgical technique. In order to stain the bone for
      histologic analysis, oxytetracycline injections were given 17 and 8 days before
      the animals were sacrificed. The animals were sacrificed 12 weeks after implant
      placement. Histomorphometric analysis indicated that there was an average bone to
      implant contact orf 68% for the test implants and 61% for the controls. There
      were no statistical differences between tests and controls. The preliminary
      results of this pilot study indicated that early bone healing for the 2 screw
      shaped implants investigated were similar.

PMID- 9151609
TI  - The influence of periodontitis on the subgingival flora around implants in
      partially edentulous patients.
AB  - The hypothesis that teeth act as reservoirs of micro-organisms for the
      colonization of oral implants has recently been stated several times. The present
      study aimed at examining, in partially edentulous patients with severe
      periodontitis, whether pockets around teeth and implants harbored a comparable
      micro-flora. In 6 patients (3 with refractory periodontitis and 3 with advanced
      chronic adult periodontitis), plaque samples were taken from a deep and shallow
      pocket around both teeth and implants for differential phase contrast microscopy
      and DNA probe analysis. The results showed important differences in the sub
      gingival flora between the 2 disease groups, as well as between deep and shallow
      pockets, around both implants and teeth. On the other hand, when pockets around
      teeth and implants with equal depths were compared a striking similarity was
      observed in the microbial composition. These observations confirm the hypothesis
      that pockets around teeth act as a reservoir and highlight the importance of
      periodontal health when oral implants are planned.

PMID- 9151610
TI  - The use of palatal implants for orthodontic anchorage. Design and clinical
      application of the orthosystem.
AB  - This paper presents the Orthosystem (Institute Straumann, Waldenburg/
      Switzerland), a new endosseous orthodontic implant anchor system for palatal
      anchorage. The Orthosystem may replace compliance dependent extraoral anchoring
      aids for orthodontics and makes a bonding of well aligned mandibular dentition
      and it's use with class II elastics unnecessary. The fixture is designed for a
      one-stage application. It consists of an implant of pure titanium with a surface
      treated, screw-shaped endosseous part of 3.3 mm diameter and lengths of 4 and 6
      mm. Above the polished transmucosal neck follows as abutment where transpalatal
      arches made of rigid orthodontic wires (0.032 x 0.032 inch) are fixed by means of
      a clamp-cap. 6 patients with an angle class II malocclusion were implanted with
      the 6 mm fixture in the proximal midsagittal region of the palate during a pilot
      study. The treatment goal was extraction of the first maxillary premolars with
      subsequent retraction of the frontal dentition under maximal anchorage of the
      lateral teeth. For the implantation a simple surgical procedure of 10 min length
      was required while no further invasive action are needed until explantation. This
      way the strain on the patients was reduced to a minimum. They are now at varying
      stages of active treatment and the most advanced case is demonstrated here. The
      clinical and radiological findings after 12 months of treatment comprising 3
      months of healing revealed no implant mobility or dislocation, favourable
      periimplant soft tissue conditions, and no marked mesial movement of the implant
      supported teeth. The frontal dentition was retracted by 8 mm with space closure
      occurring in a relatively short treatment period.

PMID- 9151611
TI  - Comparison of soft tissue healing and osseointegration of IMZ implants placed in
      one-stage and two-stage techniques: a pilot study.
AB  - The osseointegration of endosseous dental implants is well documented. Implants
      have proven to be a viable treatment option for the replacement of missing teeth.
      The surgical phase of implant dentistry for most implant systems involves two
      stages--the placement of the implant and its subsequent uncovering. The IMZ
      (Interpore International) implant system is classically a two-stage system. No
      significant differences were demonstrated in osseointegration and soft tissue
      healing for IMZ implants placed in one-stage and two-stage procedures in this
      pilot study.

PMID- 9151612
TI  - Ultimate tensile strength of five interchangeable prosthetic retaining screws.
AB  - Implant prosthetic retaining screws have been reported to serve as built-in
      safety factors to protect against overload in the implant's "vertical stack,"
      although loosening and fracture of retaining screws are often considered
      complications. Manufacturers have responded by introducing interchangeable
      prosthetic retaining screws, which can give the clinician the impression that
      interchanging screws will not have an adverse effect on the remainder of the
      implant complex and/or the integration of the implant itself. The objective of
      this investigation was to measure the ultimate tensile strength of four retaining
      screws from three manufacturers and two alloy types (gold and titanium) using the
      Nobelpharma gold prosthetic retaining screws as a standard for the comparisons.
      Five screws of each type were loaded in tension in an Instron Universal Testing
      Machine until fracture occurred. A Tukey-Kramer Test (significance level = .05)
      analysis of the data showed that all of the interchangeable prosthetic retaining
      screws were significantly different from the control screws in respect to
      ultimate tensile strength. The data suggest that interchanging prosthetic
      retaining screws will influence their built-in safety feature.

PMID- 9151613
TI  - One-step fixed edentulous implant impressions and maxillomandibular jaw
      relationships: technical note.
AB  - A custom impression tray fabricated from the diagnostic wax-up of existing
      denture can be used to simultaneously record the final impression and the
      maxillomandibular jaw relationships for edentulous implant patients. The
      technique, which also involves a soldering index for the metallic substructure,
      is easy to perform and cost effective.

PMID- 9151614
TI  - Testing progressive loading of endosteal implants with the Periotest: a pilot
      study.
AB  - The progressive loading of implants was first suggested by Misch in 1980. A major
      indicator of successful osseointegration is lack of implant mobility. In a pilot
      study, 26 implants were placed in eight patients. Fifteen of the implants were
      progressively loaded before placement of the final restorations. The remaining 11
      implants were allowed to heal with healing abutments only and were not loaded
      until placement of the final restorations. Three measurements were taken for each
      of the implants at the time of uncovering and at the final restoration
      appointment using the Periotest. The mean change in Periotest values was -0.27
      for the non-loaded group as compared with -1.51 for the progressively loaded
      group. There was a significantly larger increase (P < 0.001) in implant rigidity
      for the progressively loaded group. Progressive loading appears to enhance
      implant rigidity. The Periotest has the potential of being a valuable instrument
      for the determination of osseointegration.

PMID- 9151615
TI  - Repair of implant overdenture clip attachments: technical note.
AB  - A technique is described for repositioning the clip attachments of implant
      overdentures during repair or relining procedures using a direct method. During
      maintenance procedures, clip attachments must be repositioned correctly to
      prevent torquing of the bar and abutments and precautions taken to avoid locking
      the prosthesis to the undercut areas of the bar. This technique ensures proper
      positioning of the attachments and decreases the amount of polymerization
      shrinkage.

PMID- 9151616
TI  - Load distribution on implants with a cantilevered substructure: an in vitro pilot
      study.
AB  - The forces distributed on six Nobelpharma implants were analyzed by strain gauges
      fixed to various implant combinations that were placed in a replica of a human
      edentulous mandible and connected to a cast gold alloy superstructure. The
      mandible was supported on its lower border and the superstructure loaded in
      different locations. Although force distribution was found to be asymmetrical,
      statistical analysis revealed no significant differences. Loads applied to one
      side of the superstructure were largely carried by the implants on that side,
      demonstrating torquing of the casting in the midline. Loads applied to the
      cantilever resulted in large extension forces in implants on the opposite side of
      the fulcrum. The magnitudes of the loads distributed on the screw varied as a
      result of the combinations, inter-implant spaces, and implant locations.

PMID- 9151617
TI  - ITI World Symposium 1995. Washington, DC, April 28-29, 1995. Abstracts.

PMID- 9151618
TI  - Medical complications following successful pediatric dental treatment.
AB  - Dental treatment is usually performed without any development of medical sequela.
      However, patients can acquire serious, life threatening complications, even
      though successful dental treatment is completed. This paper presents four case
      reports of medical complications following routine pediatric dental treatment.
      The cases include: Ludwig's angina, endocarditis, brain abscess, and anesthetic
      toxicity. Many of the medical complications were caused by pre-existing
      conditions and were not necessarily direct result of dental treatment. Although
      medical complications following dental treatment cause grave concern, the dental
      practitioner can learn much from these occurrences.

PMID- 9151619
TI  - Dentinogenesis imperfecta: influence of an overdenture on gingival tissues and
      tooth mobility.
AB  - Case report of a child demonstrating severely-worn primary dentition with
      dentinogenesis imperfecta is presented. Overdentures were fabricated in order to
      preserve clinical crowns, re-establish the clinical dimension of occlusion and
      provide esthetics. The patient underwent monthly recall visits for a 6-month
      period, during which most rapid changes concerning the gingival tissues and tooth
      mobility were expected.

PMID- 9151620
TI  - Frankel appliance type III: correct fabrication and case report of skeletal Class
      III malocclusion.
AB  - The functional Regulator was developed by Rolf Frankel of Zwickau, Germany in
      1966. The Frankel appliance is used to effect changes in sagittal, transverse,
      and vertical jaw relationships and remove the abnormal muscle forces in the
      labial and buccal areas that restrict skeletal growth, thereby, providing an
      environment which maximizes skeletal growth. Four main types of functional
      regulators have been described by Frankel. They are the FR I, II, III and IV. One
      of these appliances, the FR-III, is used in the treatment of skeletal Class III
      malocclusion. This appliance is used during early mixed dentition stage to
      correct skeletal Class III malocclusion, characterized by maxillary skeletal
      retrusion and no mandibular prognathism. The correct fabrication of FR-III is
      required. In order to do it, one must pay attention to the following: mixing the
      alginate impression material in a thick consistency, optimum vestibular depth,
      oblique mounting of casts in the vertiiculator, minimum incisal vertical height
      of construction bite, sufficient working model trimming, rectangular wax relief
      of the occlusal margin area in the working cast and a palatal bow of 1.2 mm heavy
      wire. Finally one case is reported.

PMID- 9151621
TI  - The use of caries detector dye in diagnosis of occlusal carious lesions.
AB  - The purpose of this in vitro study was to compare the accuracy of diagnosis of
      carious lesions in the occlusal pit, fissure, and groove system of lower molars
      examined by two methods: examination by using caries detector dye. vs.
      traditional tactile examination using a dental explorer. Thirty human lower
      permanent molars were examined in this study. The occlusal surface of each tooth
      was examined by explorer; a linear measurement in millimeters of carious lesions
      diagnosed in the pit, fissure and groove system was recorded. The same surface
      was then stained with caries detection dye. Linear measurements in millimeters
      were then recorded for areas of stain remaining in the pit, fissure, and groove
      system. The thirty teeth were then sectioned buccal lingually in three sections,
      exposing 180 saggital histological cross sections for histological examination.
      Histological cross section confirmed a ratio of 1:1 (100%) accuracy by caries
      detection dye in diagnosing decay underlying the occlusal surface. Concurrent
      examination of the same occlusal surfaces by traditional explorer examination was
      reliable only in a 1:4 ratio (25%). Other findings of significance revealed by
      histological examination of the cross sections include: a sub-ridge occlusal
      transverse ridge of enamel; different shape and direction of occlusal grooves
      compared to traditional teaching; and unpredictable path of caries underlying the
      occlusal grooves.

PMID- 9151622
TI  - Fissure micromorphology and sealant adaptation after occlusal enameloplasty.
AB  - This study evaluated fissure micromorphology after enameloplasty, and the effect
      of thermocycling on the adaptation of enamel surfaces of filled and unfilled
      sealants after different occlusal surface treatments. A total of 150 human
      noncarious extracted molars were cleaned with a water slurry of fine flour of
      pumice using Crescent Snap-On pointed brushes in a slow-speed handpiece. The
      teeth were divided at random into six groups of 20 teeth each: Group 1: Pumice
      prophylaxis and PrismaShield filled sealant; Group 2: Pumice prophylaxis and
      Delton opaque unfilled sealant; Group 3: Treatment with a diamond fissure bur
      (Sorensen Ponta K.G. 2137 F) and PrismaShield sealant; Group 4: Treatment with a
      diamond fissure bur (Sorensen Ponta K.G. 2137 F) and Delton opaque sealant; Group
      5: Treatment with a 1/4 round carbide bur and PrismaShield sealant; Group 6:
      Treatment with a 1/4 round carbide bur and Delton opaque sealant. Before sealant
      placement, the enamel occlusal surfaces were acid-etched for 30 seconds using
      disposable brushes, rinsed and dried. The sealants were light-cured for 40
      seconds. Immediately after curing the sealant, all teeth were placed in distilled
      water for 48 hours. Sixty teeth were thermocycled (x 500, 5 degrees C-55 degrees
      C, 30-second dwell time) and 60 teeth were not thermocycled. For each treatment
      modality, five additional teeth served as controls and did not receive the
      sealant. The results revealed a superior sealant adaptation to enamel when the
      enameloplasty technique was used. There was no difference in penetration
      capabilities and adaptation between the filled and the unfilled sealants or
      between the thermocycled or not thermocycled groups.

PMID- 9151623
TI  - Electromyographic and ultrasonographic evaluation of the circum-oral musculature
      in children.
AB  - Muscle activity and thickness of the circum-oral musculature in children with
      class I molar occlusion having normal anterior relation, anterior deep-bite and
      anterior open-bite were measured using electromyographic and ultrasonographic
      techniques. The results demonstrated that the upper lip muscle thickness was
      least in open-bite subjects and lower lip muscle thickness was maximum in deep
      bite subjects. The muscle activity in both the upper and lower lip was high in
      deep-bite subjects. A significantly negative correlation between muscle activity
      and thickness was noted only in the middle and left side of the lower lip in
      subjects having normal anterior relation. The upper lip contributed to the
      maximum EMG activity in all the three groups observed.

PMID- 9151624
TI  - Influencing factors of nursing caries.
AB  - This study was done to determine some of the effecting factors in the formation
      of nursing caries. For this purpose, 161 children with nursing caries, aged 2 to
      5 years, were chosen. The control group was formed by 181 children with no
      caries. The ratio of giving up the habits in the group having nursing caries
      during the 12 months period was lower than the control group. The children
      falling asleep with the nursing caries bottle and a more incidence of nursing
      caries compared to those who did not. It was found that the type of carbohydrate
      liquid did not have a different effect in the formation of nursing caries.
      Commenced toothbrushing age did not show significant differences between those
      who developed nursing caries and those who did not. Even though the families had
      enough knowledge about the formation of caries, this was unable to stop the
      formation of the phenomenon.

PMID- 9151625
TI  - Periodontal findings in cases of posterior cross-bite.
AB  - The relationship between cross-bite and periodontal health in the posterior
      segment was investigated in 44 teenage subjects. The result did show a
      relationship between the cross-bite and periodontal health as assessed by Plaque
      Index, Gingival Index and pocket depth measurements. Pocket depth in all sites
      with the exception in the distal site for both sexes does not reach a significant
      difference between the cross-bite and the control teeth. The periodontal status
      of the teeth in cross-bite revealed a more unfavorable periodontal condition in
      males compared to the females but no statistical significant difference was
      reached.

PMID- 9151626
TI  - The time used to administer local anesthesia to 5 and 6 year olds.
AB  - Pediatric dentistry and local anesthesia textbooks recommend injecting the local
      anesthetic during dental anesthesia and the rate of 1 ml per min. On the other
      hand, there are indications that, in practice, most dentists inject the
      anesthetic considerably faster. There has been no study indicating an ideal rate.
      Fourteen 5 and 6 year olds received treatment of two operative appointments and
      the injections were videotaped. All injections were administered by the same
      dentist, who did not know that the injections would be timed. There was an equal
      number of maxillary infiltrations and mandibular blocks. Each child received the
      same type of injection in both appointments. In all cases 1.8 ml of anesthetic
      were administered and provided anesthetic effect for the operative procedures.
      Two pediatric dentists rated the behavior of the children during the injection.
      The injections were timed from tissue piercing until withdrawal of the needle and
      the times ranged between 36 seconds and 161 seconds (2 minutes 41 seconds) with
      an average of 80.67 seconds (SD:34.84). This average is about 2/3 the time
      recommended to administer 1.8 ml. No statistically significant correlation was
      found between the time it took to administer the local anesthetic and the
      behavior of the children, or between the time and whether the children saw the
      needle prior to anesthesia administrator. The data presented no evidence to
      suggest that varying the time it takes to administer one capsule of anesthetic
      between 36 and 161 seconds affects the behavior of the children of the success of
      the anesthesia.

PMID- 9151627
TI  - Natal teeth: case report.
AB  - The natal teeth are defined as the presence of teeth at birth and the etiology is
      rather obscure. Clinically, the teeth show normal size and shape, although they
      reveal an immature appearance. The histological aspect show enamel with the
      possibility of presenting normal mineralization or being hypoplastic. The dentin
      may show alterations. The incidence of natal teeth varies greatly, with a
      predisposition for the female sex. This paper relates a case report of two
      partially erupted natal teeth in a female baby 9 days-old. The presence of teeth
      made the parents anxious. In their mind, that meant the child was abnormal. On
      the radiograph the erupted teeth showed little radio-opacity, without a radicular
      formation. The therapy utilized was the keeping of the teeth and a periodic
      monitoring, cleaning and daily topical applications sodium fluoride. The case was
      monitored by monthly consultations. At 9 months of age the primary central lower
      did not present mobility. On the radiograph examination incomplete radicular
      formation was observed.

PMID- 9151628
TI  - Orofaciodigital syndrome I: a case report.
AB  - Orofaciodigital syndrome I is a syndrome, which affects the maxillofacial region.
      Abnormally developed vestibular frenulum, cleft tongue, asymmetric cleft palate,
      pseudocleft of the upper lip and hypoplasia of the nasal cartilages are some of
      the other features. There are some malformations in foot and hand fingers and
      also mild mental deficiency is present. OFD I syndrome follows an chi-linked
      dominant mode of transmission trait limited to females and lethal in males.
      Because of the esthetic and functional manifestations in the maxillofacial
      region, the syndrome has great importance for pediatric dentistry.

PMID- 9151630
TI  - Local, hypoplastic type of amelogenesis imperfecta: a clinical, genetic,
      radiological and dermatoglyphic study.
AB  - A patient and her family members showing X-linked dominant form local,
      hypoplastic type of amelogenesis imperfecta (AI) were investigated from view
      point of their teeth, clinical, genetic, radiological and particularly
      dermatoglyphic findings. It was suggested that it might be a close relationship
      between the intra-uterine development of both AI and unusual dermatoglyphs
      originated from the same layer, ectoderm and an X-linked dominant gene could
      determine both abnormal teeth and unusual dermatoglyphic characteristics in
      questions.

PMID- 9151629
TI  - Chlorhexidine spray effects on plaque accumulation in developmentally disabled
      patients.
AB  - Chlorhexidine gluconate has been studied as an adjunct to standard oral hygiene
      techniques in developmentally disabled patients in reducing plaque accumulation.
      The purpose of this double blind crossover study was to determine the efficacy of
      two concentrations of chlorhexidine spray (0.12% and 0.06%) on plaque
      accumulation in developmentally disabled patients. Informed consent was obtained
      for 8 developmentally disabled patients 12 to 33 years of age. Patients were
      randomly assigned to one of two groups of four each. One group received twice
      daily 0.12% chlorhexidine spray while the other received the 0.06% chlorhexidine
      spray for 30 days, followed by twice daily chlorhexidine spray (0.12% and 0.06%)
      alternating groups, for a period of 30 days. Final plaque indices were
      determined. Normal oral hygiene practices continued throughout the study.
      Significant plaque reduction occurred with the 0.12% and 0.06% spray solutions.
      No significant differences occurred between the two concentrations. The results
      of this study suggest that twice daily chlorhexidine spray at a concentration of
      0.06% is as effective in reducing plaque accumulation as a 0.12% chlorhexidine
      concentration.

PMID- 9151631
TI  - Viva the Academy! An advertisement for ourselves.

PMID- 9151632
TI  - The experimental verification of the efficacy of finite element modeling to
      dental implant systems.
AB  - In vitro experimental data of angular displacement vs. applied force were
      obtained on a fully osseointegrated pair of endosseous implants in a mandible of
      a macaca mulatta monkey. These data are compared with calculated displacement
      data for a given force from a three-dimensional finite element model reproducing
      the geometric structure of a portion of the mandible holding the implants. The
      displacements show agreement over a range of forces in the elastic region within
      3%. The FE model yields a full description of the bending of the implant and the
      distribution of the stress in the bone surrounding the implants.

PMID- 9151633
TI  - Types, uses, and evaluation of the plate-form implant.
AB  - Plate-form blades have shown a high rate of success over their 25+ years of
      service. Contributing to their longevity is the design of the implant, which
      transfers the applied forces over a large area of bone. Three types of implants
      are being considered: (1) the Ramus Blade, designed for the body and ramus region
      of the mandible; (2) the Ramus Frame, designed for the totally edentulous
      mandible with moderate to severe bone atrophy; and (3) the single-tooth
      replacement, an implant for single or multiple tooth loss. Both 316-L stainless
      steel and titanium metal types have been used to fabricate each implant type.
      Blades are, in the author's opinion, the most universal of the implants used
      today, for they are utilized in so many variable bone widths and heights. Besides
      being in service for periods of up to 27 years, they are patient-acceptable in
      terms of comfort, function and minimal maintenance.

PMID- 9151634
TI  - Sinus grafting related to implantology. Statistical analysis of 15 years of
      surgical experience (1979-1994).
AB  - Sinus cavities are often a major obstacle to the placement of dental implants in
      the posterior maxilla, especially when early tooth loss has occurred. Several
      grafting procedures aimed at reducing the expanded volume of these pneumatic
      cavities have been routinely utilized since 1979. Essentially, these techniques
      have consisted of recreating the necessary viable bone volume at the floor of
      sinus cavities by placing different bone substitute materials to allow for the
      insertion of endosseous implant devices. The progress achieved in the refinement
      of the surgical procedures and the knowledge acquired in the field of patient
      screening and selection, choice of biomaterials, management of complications,
      etc., have made sinus graft surgery highly codified and predictable. A
      comprehensive statistical study by multifactorial procedures was carried out to
      establish a Burt Contingency Chart. This chart visualizes the frequencies of all
      the "modality combinations" among the selected "qualitative parameters" and, by a
      " factorial analysis", the "multiple correlations", so that the "statistical
      affinities" that may exist among the same variables can be determined. This
      critical study endeavors to search for and reveal the favorable clinical,
      biologic and scientific parameters necessary for the success of sinus graft
      surgery on short-, medium-, and long-term bases (more than nine years). It is a
      particularly homogenous study, since all the operative procedures have been
      carried out exclusively by the author under standardized conditions. The wide
      variety of biomaterials utilized by the author since 1979 shows the development
      of bone substitute biomaterials as they have been introduced into the market
      during the past 15 years. The large number of patients treated, the variety of
      grafting materials, the important success rate obtained, and the long duration of
      patient follow-up have been instrumental in enabling us to establish
      scientifically significant results. Autogenous bone and its combinations with
      calcium- and phosphorus-containing biomaterials remain undoubtedly the best all
      purpose biomaterials. The synthetic biomaterials have their own specific
      indications according to their stable (non-resorbable) or unstable (resorbable)
      nature and their rates of metabolic "turnover". Differently treated bones from
      the tissue bank (if not contaminated or immunologically questionable) behave in a
      fashion not unlike autogenous bone. Root-form implants are by far the best
      implants in the reconstructed sinus sites, while other implant types
      (subperiosteal implants, etc.) inserted beneath the reinforced osseous sinus
      floor, buccal wall, and pyramidal process, also have their indications.

PMID- 9151635
TI  - Cast titanium dental implants for the posterior mandible.
AB  - The purpose of this paper is to present the results of the evaluation of five
      patients who received titanium dental implant replicas of extracted molars and
      pre-molars, placed in the posterior mandible. The replicas were placed in the
      sockets where the molars and bicuspids had been extracted. The implant replicas
      were fabricated in two parts, an abutment portion and a root portion connected by
      a titanium screw. The root portion was made of cast titanium. The abutment
      portion was made of a high noble metal to which porcelain could be fused, so that
      the crown restoration could be made directly on the abutment. The patient's ages
      ranged from 27 to 63 years. Four were male and one was female. The implants were
      placed three to six weeks after extraction. All implants integrated. The longest
      follow-up with the implant in function was five years.

PMID- 9151637
TI  - Pre-surgical dental implant assessment by magnetic resonance imaging.
AB  - The use of magnetic resonance imaging (MRI) for pre-surgical implant assessment
      of available bone in the maxilla and mandible is described. An acrylic surgical
      template with suitable MRI reference markers allows potential implant sites, as
      chosen on the MR images, to be accurately identified at surgery. MRI is a
      tomographic modality capable of giving accurate information on the three
      dimensional relationships of all the relevant anatomic structures. Our results
      show that MRI is reasonably tolerant of artifacts caused by metal pins and
      amalgam fillings. Unlike computerized tomography (CT) and other x-radiographic
      techniques, MRI uses no ionizing radiation, and is capable of angulating and
      offsetting its scan plane at will. Good bone detail is available because
      cancellous bone yields a strong signal from the marrow fat, while cortical bone
      and dental enamel are dark. The excellent anatomic detail provided by thin-slice
      high-resolution MRI allows for assessment of the suitability of sites to receive
      an implant in terms of bone quality and thickness, and the relative position of
      the site to important structures such as the inferior dental nerve and nasal
      sinuses. The MRI technique used is described in detail. The principles underlying
      image contrast are outlined where appropriate and examples shown. To date, we
      have used MRI in conjunction with rotational panoramic x-rays (OPG) to plan 26
      implants (21 maxillary, 5 mandibular) in 12 patients.

PMID- 9151636
TI  - Recovery of alveolar bone by the guided bone regeneration technique.
AB  - Bone defects associated with the removal of endosteal implants often create
      challenging problems for clinicians. The guided bone regeneration (GBR) technique
      has been recently used in the treatment of such defects, and promising results
      have been obtained. This report describes the use of Gore-Tex tissue augmentation
      material (GTAM) membranes after the removal of Bioceram screw implants in two
      patients who wore the implants for 10 years and seven years, respectively. After
      removal, the residual bone defects were treated by the GBR technique. Bone
      regeneration was confirmed in the defects around the newly placed implants, and
      decreased bone mass was avoided in both patients. In case 1, a free gingival
      graft was used to increase the area of attached gingiva around the implants,
      since the status of peri-implant soft tissue is also crucial to the outcome of
      therapy. This technique was very effective in maintaining an adequate width of
      attached gingiva.

PMID- 9151638
TI  - Serum immunoglobulin G responses to various Actinobacillus actinomycetemcomitans
      serotypes in a young ethnographically heterogeneous periodontitis patient group.
AB  - Sera from young patients with periodontal diseases have been shown to often
      contain highly elevated antibody levels to Actinobacillus actinomycetemcomitans,
      in particular serotype b. Such responses were reportedly predominated by
      antibodies of the immunoglobulin G2 (IgG2) subclass. The aim of this study was to
      investigate an ethnically diverse group of 14 early-onset periodontitis and 15
      rapidly progressive periodontitis patients for the occurrence of elevated
      antibody titers against the five known A. actinomycetemcomitans serotypes, and to
      compare the patient's IgG subclass response profiles. Enzyme-linked immunosorbent
      assays were used to measure both total IgG and subclass specific IgG titers.
      Twenty-four subjects had markedly elevate total IgG levels against at least one
      serotype. The frequencies of high responses against serotypes a, b, c, d and e
      were 7, 11, 6, 4, and 4, respectively. Elevated antibody responses were
      predominated by IgG2, regardless of the serotype to which the response was
      directed. The serotype specificity of the host responses was further investigated
      by competitive binding studies with serotype-specific monoclonal antibodies.
      Twelve sera were found to contain antibodies capable of strongly inhibit the
      binding of monoclonal antibodies against a single serotype; four other sera had
      antibodies against epitopes of two, and one serum against those of three
      serotypes. The findings document broad serotype diversity in an ethnically
      heterogeneous group of patients and indicate that strong antibody responses to A.
      actinomycetemcomitans are predominated by IgG2 regardless of the serotype of the
      infective agent.

PMID- 9151639
TI  - Recognition of antigenic epitopes in lipopolysaccharide and protein from
      Actinobacillus actinomycetemcomitans by serum antibodies in untreated rapidly
      progressive periodontitis patients.
AB  - Actinobacillus actinomycetemcomitans has been associated with early-onset
      periodontitis, including the localized juvenile and rapidly progressive forms.
      The immunodominant antigens of A. actinomycetemcomitans recognized by rapidly
      progressive periodontitis patients remain unidentified. Sera from 22 patients
      with rapidly progressive periodontitis and 20 periodontally normal subjects were
      tested by enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G
      antibodies to whole-cell sonicate, protein, purified lipopolysaccharide and
      lipopolysaccharide fractions of A. actinomycetemcomitans. The median titers of
      rapidly progressive periodontitis patients and control subjects to whole-cell
      sonicate were 25.0 and 14.5 ELISA units, respectively (not significantly
      different). Binding of antibody from patient sera occurred to both the
      lipopolysaccharide and the protein fractions, with greater binding to
      lipopolysaccharide than to protein. We show for the first time that patient sera
      contain antibodies that bind specifically to antigenic epitopes in lipid A and in
      the core carbohydrate of lipopolysaccharide that were previously considered to be
      inaccessible and unavailable, as well as to epitopes in the O side chains. Sera
      manifesting antibody titers 2-fold or greater than the median titer for control
      sera were judged to be seropositive. More patients were seropositive for lipid A
      than for any of the other antigen preparations studied, and the median titer for
      patient sera to lipid A but to none of the other purified lipopolysaccharide
      fractions was significantly elevated relative to control values. Of 22 patients,
      10 were seropositive to whole-cell sonicate, 7 to protein, 8 to
      lipopolysaccharide, 7 to the high-molecular-weight lipopolysaccharide
      polysaccharide fraction rich in O side chains, and 16 to lipid A. The core
      carbohydrate did not adhere to the test plate surface, and this precluded ELISA
      measurements. However, when the core carbohydrate was used in the ELISA
      inhibition assay, it reduced antibody binding to lipopolysaccharide-coated plates
      by up to 45%, thereby demonstrating antibody binding to core carbohydrate. The
      core carbohydrate fraction from the Re mutant of Salmonella minnesota known to
      contain no O-side chains also inhibited binding of specific antibody to plates
      coated with A actinomycetemcomitans lipopolysaccharide. Overall, there was
      extreme variation in responses among patients to the various antigen
      preparations, with no single pattern dominating. Lipopolysaccharide and its
      components appear to be the immunodominant epitopes, since most rapidly
      progressive periodontitis patients are seropositive for lipopolysaccharide and/or
      its components and they have titers relative to those for proteins.

PMID- 9151640
TI  - Antibody reactive with Actinobacillus actinomycetemcomitans leukotoxin in early
      onset periodontitis patients.
AB  - The objective of this study was to determine whether a relationship exists
      between antibody reactive with the Actinobacillus actinomycetemcomitans
      leukotoxin and the severity of periodontal disease. Serum concentrations of
      antibody reactive with the leukotoxin were determined for 119 early-onset
      periodontitis patients and 59 non-periodontitis subjects using limiting dilution
      analysis on Western blots. Immunoglobulin G (IgG) antibody reactive with the A.
      actinomycetemcomitans leukotoxin ranged from undetectable to 29 micrograms/ml
      (mean = 3.13 +/- 0.97 micrograms/ml for the generalized early-onset periodontitis
      and 2.17 +/- 0.86 micrograms/ml for the localized juvenile periodontitis patients
      vs 0.32 +/- 0.24 ng/ml for 59 non-periodontitis controls), and the dominant
      subclass was IgG1. Analysis of the relationship between antibody reactive with A.
      actinomycetemcomitans sonicate, A. actinomycetemcomitans leukotoxin and
      attachment loss patterns indicates that seropositive generalized early-onset
      periodontitis patients had decreased attachment loss compared with patients
      lacking this antibody. The statistical relationship appeared to be stronger for
      the sonicate than the purified leukotoxin. These data suggest that antibody
      reactive with A. actinomycetemcomitans leukotoxin may be protective in early
      onset periodontitis, but given that the sonicate appeared better than the
      leukotoxin alone, it is not likely that leukotoxin is the only antigen of
      importance to host defense.

PMID- 9151641
TI  - Myeloperoxidase isoform activities released by human neutrophils in response to
      dental and periodontal bacteria.
AB  - Myeloperoxidase is an enzyme released by polymorphonuclear leukocytes which has
      been used, experimentally, as an indicator of periodontal disease activity when
      measured in gingival crevicular fluid. There are three myeloperoxidase isoforms:
      MPO I, MPO II and MPO III. We examined the activities of myeloperoxidase isoforms
      released by neutrophils in response to serum-opsonized Actinobacillus
      actinomycetemcomitans, Haemophilus aphrophilus, Eikenella corrodens,
      Capnocytophaga sputigena and Streptococcus sanguis. Isoform activities were
      determined using intermediate-pressure liquid chromatography and microenzyme
      assay. A. actinomycetemcomitans stimulated higher levels of myeloperoxidase
      release than any other oral bacteria unless pre-opsonized with serum (or protein
      A-purified immunoglobulin) from an individual with localized juvenile
      periodontitis. Most oral bacteria stimulated the release of all myeloperoxidase
      isoforms with a profile enriched in MPO I and diminished in MPO III.
      Exceptionally, serum-opsonized A. actinomycetemcomitans stimulated
      myeloperoxidase isoform release in proportion to the neutrophil granule
      constituency with or without localized juvenile periodontitis serum pre
      opsonization. Because myeloperoxidase isoform profiles reflect how neutrophils
      were stimulated, isoform analysis may refine future diagnostic tests based upon
      myeloperoxidase.

PMID- 9151642
TI  - Investigation of the Actinobacillus actinomycetemcomitans genome by pulsed field
      gel electrophoresis.
AB  - Pulsed field gel electrophoresis was used to investigate nineteen strains of
      Actinobacillus actinomycetemcomitans. The genome was found to contain a single
      chromosome whose size we estimate to be 2300 kb from the sum of restriction
      fragments generated with rare cutting endonucleases. We detected the presence of
      large plasmids with sizes ranging from 35 to 300 kb. In some strains,
      extrachromosomal elements constitute over 20% of the total genome. Comparison of
      the profiles of ApaI digests of the 19 strains showed a high degree of
      polymorphism with 13 different profiles, providing a new tool for epidemiological
      studies.

PMID- 9151643
TI  - Occurrence of temperate bacteriophages in different Actinobacillus
      actinomycetemcomitans serotypes isolated from periodontally healthy individuals.
AB  - The occurrence of temperate bacteriophages was studied in 34 isolates of
      Actinobacillus actinomycetemcomitans derived from 27 periodontally healthy
      Finnish individuals both by lysis/plaque assays and by DNA hybridizations. In
      addition the serotype, the ribotype and the arbitrarily primed polymerase chain
      reaction (AP-PCR) profile were determined for each A. actinomycetemcomitans
      strain. Fourteen isolates showed hybridization patterns very similar to that of a
      known lysogen when probed with the genome of the previously characterized
      temperate phage Aa phi 23. Only 6 of these 14 strains had produced lysis or
      single plaques on suitable indicator strains. Phage Aa phi 247 derived from one
      of these lysogens was indistinguishable from Aa phi 23 by electron microscopy,
      and the genomes showed highly related DNA hybridization patterns. The remaining
      20 isolates exhibited hybridization patterns very different from that of Aa phi
      23 DNA. Seven of these strains also gave lysis or single plaques, suggesting that
      21 of the 34 strains were lysogenic. These data indicate that the prophages per
      se do not represent a virulence factor exclusively associated with periodontal
      disease. Presence of an Aa phi 23-related prophage correlated with serotype a and
      AP-PCR type 1 of the bacterial host. This may indicate that Aa phi 23 and related
      phages have a limited host range.

PMID- 9151644
TI  - Hemagglutinin activity and heterogeneity of related Porphyromonas gingivalis
      proteinases.
AB  - Thiol-dependent proteinases that are expressed and released by Porphyromonas
      gingivalis are considered virulence factors in periodontitis because of their
      potential to effect matrix degradation and inflammation. A number of P.
      gingivalis thiol-proteinases have been described, however, with similar
      biochemical characteristics. In this report we demonstrate that an isolate P.
      gingivalis proteinase consists of noncovalently associated peptides and that
      slight variations in the association pattern of these peptides could result in
      different proteinases with different affinities and activities. We also describe
      the co-purification of thiol-proteinase activity with hemagglutinin activity and
      demonstrate that each type of activity has similar inhibition profiles. With the
      use of monoclonal antibodies against the P. gingivalis proteinase we follow
      proteinase released into the culture medium over the course of 10 days and, by
      Western blot analysis, demonstrate that many of the proteinases with varying
      molecular weight are related. The identification of a single, immunoreactive, 140
      kDa proteinase detected early in the culture and in association with the P.
      gingivalis cells suggests that multiple proteinase may originate from a single
      140 kDa proteinase.

PMID- 9151645
TI  - Age-related changes in salivary antibodies to commensal oral and gut biota.
AB  - The prevalence of mucosally derived infections appears to increase with age,
      suggesting dysfunction at the mucosal surfaces. The present investigation was
      undertaken to examine any age-related changes in secretion rates and
      concentrations of secretory antibodies in whole and parotid saliva in a healthy
      adult population. A total of 116 subjects were subdivided into the following age
      groups: 20-39 years, 40-59 years, 60-79 years and 80 years and over. Specific
      immunoglobulin A (IgA), IgG and IgM antibodies in whole and parotid saliva to
      Streptococcus mutans (serotype c), Actinomyces viscosus NCTC 10951, and
      Escherichia coli NCTC 10418 were quantified by enzyme-linked immunosorbent assay.
      IgA antibodies to all three organisms examined increased with age in both whole
      and parotid saliva, whereas IgG antibody levels to S. mutans in whole saliva were
      significantly decreased with age. IgG antibodies to E. coli in parotid saliva
      were reduced in older age groups. IgM antibody levels to S. mutans were reduced
      with age in both secretions, whereas IgM antibodies to A. viscosus were greatest
      in the oldest age groups. No significant changes with age were observed in
      salivary IgM antibody levels to E. coli. No significant reduction in the
      secretion rates of IgA antibodies were observed in parotid or whole saliva,
      whereas IgG and IgM antibody secretion rates to all three microorganisms were
      reduced in most age groups in both whole and parotid saliva. The results of this
      investigation have demonstrated age-related changes with salivary antibodies,
      but, whereas salivary IgG and IgM antibodies showed decreases, salivary IgA
      levels generally increased with age. This suggests that the ability to form IgA
      antibody responses is not impaired with increased age, and that secretion rates
      and functional properties of antibodies may be as important as concentrations in
      protection against mucosal infective diseases.

PMID- 9151647
TI  - The future of mental health research in primary care settings.

PMID- 9151646
TI  - The US National Comorbidity Survey: overview and future directions.

PMID- 9151648
TI  - The future of psychiatric case register studies.

PMID- 9151649
TI  - The future of mental health services research.

PMID- 9151650
TI  - Advocacy in the mental health services field.
AB  - Advocacy in the mental health services field is gaining importance since the
      traditional role of mental health hospitals is changing, particularly in North
      America and in Western Europe. This review will define advocacy, its goals and
      fundamental principles. It will then delineate the skills and strategies needed
      for any intervention on behalf of a patient or a group of patients. It will also
      deal with the issues and approaches most frequently raised and used, and finally,
      with the limits of advocacy. METHOD: The method used for this review was mainly a
      recension of the literature concerning advocacy throughout North America and
      Europe, having in view to see emerging the principal stakes and concerns related
      to this process. RESULTS: Advocacy has a significant impact on patients'
      awareness of their rights and their capacity to exercise them. It also prevents
      potential abuse of patients. On the other hand, some patients have an increased
      opportunity to cease treatment, and this could lead to serious medical
      consequences. There is also the possibility of retaliation from staff, as a
      result of being involved with an advocate. The combination of high quality care
      and effective advocacy is the best guarantee that a mental health patient will
      get the care he wants and needs with human dignity.

PMID- 9151651
TI  - The contribution of epidemiology to psychosomatic medicine.
AB  - OBJECTIVE: To discuss the contribution of epidemiology and epidemiological
      methods to psychosomatic medicine. METHOD: Critical review of the literature,
      including both philosophical concepts and empirical data. RESULTS: The adjective
      "psychosomatic" has been used in two different ways: in the so called
      "psychosomatic" or holistic approach to medicine; and in a narrower approach,
      referring to particular disorders in which psychological factors were considered
      to have a fundamental aetiological role. While the ideal of the holistic,
      "humanistic" or "anthropological" approach should probably be never abandoned,
      the practical limitations of encompassing models, including Engel's bio-psycho
      social model are also obvious: they may be heuristically sterile. On the other
      side, in relation to the narrow psychosomatic approach, psychogenetic views in
      the so called "psychosomatic illnesses" have been strongly criticized on
      empirical grounds. The potential of epidemiological methods to study these
      illnesses, but also "somatopsychic" disorders is shown in a number of papers in
      the empirical literature. We have grouped such contributions, including our own
      experience, in the five categories suggested by M. Shephered for epidemiological
      methods in general: 1) the completion of the spectrum of disease; 2) the
      establishment of outcome; 3) the actuarial assessment of morbid risk; 4) the
      evaluation of the efficacy of treatment; and 5) the conceptual construction of
      diagnosis and classification. CONCLUSIONS: The contribution of epidemiological
      data to areas of interest in psychosomatic medicine has been relevant in recent
      years. The potential of epidemiological methods in this area is very important
      both to increase knowledge and to improve the quality of clinical practice.

PMID- 9151652
TI  - Protein transport from the cytoplasm into the vacuole.
AB  - The fungal vacuole is integrally involved in various cellular processes that
      include protein and organellar degradation and recycling. The ability to
      sequester numerous hydrolases within the cell makes the hydrolytic capacity of
      the vacuole critical under certain environmental conditions. Accordingly,
      cellular constituents destined for degradation are delivered to the vacuole
      through the secretory pathway, by endocytosis and from the cytoplasm. Different
      mechanisms have evolved to accommodate these multiple transport pathways. Protein
      transport from the cytoplasm into the vacuole in particular relies on the dynamic
      nature of the vacuole membrane. This review describes recent research on this
      topic from yeast systems and points out the direction of future studies aimed at
      understanding this complex organelle.

PMID- 9151653
TI  - The H+ pump in frog skin (Rana esculenta): identification and localization of a V
      ATPase.
AB  - We here report on studies on the frog skin epithelium to identify the nature of
      its excretory H+ pump by comparing transport studies, using inhibitors highly
      specific for V-ATPases, with results from immunocytochemistry using V-ATPase
      directed antibodies. Bafilomycin A1 (10 microM) blocked H+ excretion (69 +/- 8%
      inhibition) and therefore Na+ absorption (61 +/- 17% inhibition after 60 min
      application, n = 6) in open-circuited skins bathed on their apical side with a 1
      mm Na2SO4 solution, "low-Na+ conditions" under which H+ and Na+ fluxes are
      coupled 1:1. The electrogenic outward H+ current measured in absence of Na+
      transport (in the presence of 50 microM amiloride) was also blocked by 10 microM
      bafilomycin A1 or 5 microM concanamycin A. In contrast, no effects were found on
      the large and dominant Na+ transport (short-circuit current), which develops with
      apical solutions containing 115 mm Na+ ("high-Na+ conditions"), demonstrating a
      specific action on H+ transport. In immunocytochemistry, V-ATPase-like
      immunoreactivity to the monoclonal antibody E11 directed to the 31-kDa subunit E
      of the bovine renal V-ATPase was localized only in mitochondria-rich cells (i) in
      their apical region which corresponds to apical plasma membrane infoldings, and
      (ii) intracellularly in their neck region and apically around the nucleus. In
      membrane extracts of the isolated frog skin epithelium, the selectivity of the
      antibody binding was tested with immunoblots. The antibody labeled exclusively a
      band of about 31 kDa, very likely the corresponding subunit E of the frog V
      ATPase. Our investigations now deliver conclusive evidence that H+ excretion is
      mediated by a V-ATPase being the electrogenic H+ pump in frog skin.

PMID- 9151654
TI  - The chloride conductance of tight junctions of rat ileum can be increased by cAMP
      but not by carbachol.
AB  - It is well known, that in mammalian small intestine, cAMP increases Cl-
      permeability of the apical membrane of enterocytes as part of its secretory
      action. Paradoxically, this is usually accompanied by an increase of the
      transepithelial resistance. In the present study we report that in the presence
      of bumetanide (to block basolateral Cl- uptake) cAMP always decreased the
      transepithelial resistance. We examined whether this decrease in resistance was
      due to a cAMP-dependent increase of the paracellular electrolyte permeability in
      addition to the increase of the Cl- permeability of the apical cell membrane. We
      used diffusion potentials induced by serosal replacement of NaCl, and
      transepithelial current passage to evoke transport number effects. The results
      revealed that cAMP (but not carbachol) could increase the Cl- permeability of the
      tight junctions in rat ileum. Moreover, we observed a variation in
      transepithelial resistance of individual tissue preparations, inversely related
      to the cation selectivity of the tissue, suggesting that Na+ permeability of the
      tight junctions can vary between preparations.

PMID- 9151655
TI  - Characterization of the high-affinity verapamil binding site in a plant plasma
      membrane Ca2+-selective channel.
AB  - Despite biochemical evidence for the existence of high-affinity phenylalkylamine
      receptors in higher plants, their effects on channel activity have only been
      demonstrated at relatively high concentrations. We have performed a quantitative
      single-channel analysis of the changes induced by extracellular verapamil in the
      rca channel [a wheat root plasma membrane Ca2+-selective channel (Pineros &
      Tester, 1995. Planta 195:478-488)]. Concentrations as low as 0.5 microM verapamil
      induced a blockade of the inward current, with no evident reduction of the single
      channel current amplitude. Blockade by verapamil was concentration and voltage
      dependent. Preliminary analysis suggested the blockade was due to a reduction in
      the maximum open state probability rather than a change in V0.5. Further analysis
      of the association and dissociation rate constants revealed a binding site
      located 56 to 59% down the voltage drop from the extracellular face of the
      channel, with a Kd(0) of 24 to 26 microM. This results in a Kd at -100 mV of 2
      microM. Methoxyverapamil had qualitatively the same effects. This intra-pore
      binding site can be accessed directly from the extracellular side of the rca
      channel, but apparently not from the cytosolic side.

PMID- 9151656
TI  - Inositol polyphosphates modify the kinetics of a small chloride channel in
      skeletal muscle sarcoplasmic reticulum.
AB  - The actions of D-myo-inositol 1,4,5-trisphosphate (IP3) and D-myo-inositol
      1,3,4,5-tetrakisphospate (IP4) on small chloride (SCl) channels from rabbit
      skeletal muscle sarcoplasmic reticulum are reported. We find that the inositol
      polyphosphates (6-40 microM) are potent reversible blockers of SCl channels in
      lipid bilayers at -40 mV with >10(-5) m cis (cytoplasmic) Ca2+ when added to the
      cis, but not trans, chamber. IP3 or IP4 at 20 microM reduced the mean open time
      from 89 +/- 16 msec to 11 +/- 2 msec or to 8.0 +/- 1.0 msec respectively, by
      abolishing the longest time constant component in the open time distribution.
      Neither IP3 nor IP4 altered the six single-channel conductance levels. The
      fraction of low conductance events increased approximately 4-fold and the dwell
      time at the lower conductance levels increased approximately 3-fold. Channel
      gating was altered so that most transitions were between the closed level and an
      open level, in contrast to control channels which remained open for long periods
      with many transitions between the six open levels. The actions of the inositol
      polyphosphates were: (1) not prevented by 20 microg/ml cis heparin (an IP3
      receptor blocker); (2) mimicked by 10 microM cis synthetic inositol
      polyphosphates, L-chiro-inositol 1,4,6-trisphosphate and L-chiro-inositol 1,4,6
      trisphosphorothionate (which do not bind to IP3 receptors); (3) mimicked by cis
      additions of the polyanions heparin or hepran (20 microg/ml each) and vanadate
      (500 microM). The results suggest that an interaction between polyanions and SCl
      channels would allow the channels to be modulated in vivo by inositol
      polyphosphates.

PMID- 9151657
TI  - Extracellular GTP causes membrane-potential oscillations through the parallel
      activation of Mg2+ and Na+ currents in Paramecium tetraurelia.
AB  - Paramecium tetraurelia responds to extracellular GTP (>/= 10 nm) with repeated
      episodes of prolonged backward swimming. These backward swimming events cause
      repulsion from the stimulus and are the behavioral consequence of an oscillating
      membrane depolarization. Ion substitution experiments showed that either Mg2+ or
      Na+ could support these responses in wild-type cells, with increasing
      concentrations of either cation increasing the extent of backward swimming.
      Applying GTP to cells under voltage clamp elicited oscillating inward currents
      with a periodicity similar to that of the membrane-potential and behavioral
      responses. These currents were also Mg2+- and Na+-dependent, suggesting that GTP
      acts through Mg2+-specific (IMg) and Na+-specific (INa) conductances that have
      been described previously in Paramecium. This suggestion is strengthened by the
      finding that Mg2+ failed to support normal behavioral or electrophysiological
      responses to GTP in a mutant that specifically lacks IMg ("eccentric"), while Na+
      failed to support GTP responses in "fast-2," a mutant that specifically lacks
      INa. Both mutants responded normally to GTP if the alternative cation was
      provided. As IMg and INa are both Ca2+-dependent currents, the characteristic GTP
      behavior could result from oscillations in intracellular Ca2+ concentration.
      Indeed, applying GTP to cells in the absence of either Mg2+ or Na+ revealed a
      minor inward current with a periodicity similar to that of the depolarizations.
      This current persisted when known voltage-dependent Ca2+ currents were blocked
      pharmacologically or genetically, which implies that it may represent the
      activation of a novel purinergic-receptor-coupled Ca2+ conductance.

PMID- 9151658
TI  - Immunolocalization of lacrimal gland PKC isoforms. Effect of phorbol esters and
      cholinergic agonists on their cellular distribution.
AB  - In previous studies, we showed that lacrimal gland acini express three isoforms
      of protein kinase C (PKC): PKCalpha,-delta, and -epsilon. In the present study,
      we report the identification of two other PKC isoforms, namely PKCmu and 
      iota/lambda. Using immunofluorescence techniques, we showed that these isoforms
      are differentially located. PKCalpha and -mu showed the most prominent membrane
      localization, whereas PKCdelta, -epsilon and -iota/lambda were mainly cytosolic.
      Using cell fractionation and western blotting techniques, we showed that the
      phorbol ester, phorbol 12,13-dibutyrate (PdBu, 10(-6) M), translocated all PKC
      isoforms, except PKCiota/lambda, from the soluble fraction into the particulate
      fraction. The effect was maximum at 5 min and persisted at 10 min. PKCepsilon was
      the most responsive to PdBu reaching almost maximal translocation at a PdBu
      concentration as low as 10(-9) M. The cholinergic agonist, carbachol (10(-5) and
      10(-3) M), induced translocation which was transient for PKCdelta, and -mu, but
      persisted for 10 min for PKCepsilon. Carbachol did not translocate PKCalpha and,
      like PdBu, did not translocate PKCiota/lambda. We concluded that lacrimal gland
      PKC isoforms are differentially localized and that they translocate
      differentially in response to phorbol esters and cholinergic agonists.

PMID- 9151659
TI  - The antifungal imidazole clotrimazole and its major in vivo metabolite are potent
      blockers of the calcium-activated potassium channel in murine erythroleukemia
      cells.
AB  - Clotrimazole (CLT), a member of the antifungal imidazole family of compounds, has
      been found to inhibit both calcium (Ca2+)-activated 86Rb and potassium (K) fluxes
      of human red cells and to inhibit red cell binding of 125I-charybdotoxin (ChTX)
      [11]. We have now used patch-clamp techniques to demonstrate reversible
      inhibition of whole cell KCa2+ currents in murine erythroleukemia (MEL) cells by
      submicromolar concentrations of CLT. Inhibition was equivalent whether currents
      were elicited by bath application of the Ca2+ ionophore A23187 or by dialyzing
      cells with a pipette solution containing micromolar concentrations of free Ca2+.
      The extent of inhibition of whole cell MEL KCa2+ currents was voltage-dependent,
      decreasing with increasing test potential. We also determined the single channel
      basis of the CLT inhibition in MEL cells by demonstrating the inhibition of a
      calcium-activated, ChTX-sensitive K channel by CLT in outside-out patches. The
      channel was also blocked by the des-imidazolyl metabolite of CLT, 2-chlorophenyl
      bisphenyl-methanol (MET II) [15], thus demonstrating that the imidazole ring is
      not required for the inhibitory action of CLT. Single KCa2+ channels were also
      evident in inside-out patches of MEL cells. Block of K current by CLT was not
      unique to MEL cells. CLT also inhibited a component of the whole cell K current
      in PC12 cells. Channel specificity of block by CLT was determined by examining
      its effects on other types of voltage-sensitive currents. CLT block showed the
      following rank order of potency: K currents in PC12 cells > Ca2+ currents in PC12
      cells >> Na currents in sympathetic neurons. These results demonstrate that
      direct inhibition of single KCa2+ by CLT can be dissociated from inhibition of
      cytochrome P-450 in MEL cells.

PMID- 9151660
TI  - Role of Cl- in electrogenic H+ secretion by cortical distal tubule.
AB  - The presence of an electrogenic H+-ATPase has been described in the late distal
      tubule, a segment which contains intercalated cells. The present paper studies
      the electrogenicity of this transport mechanism, which has been demonstrated in
      turtle bladder and in cortical collecting duct. Transepithelial PD (Vt) was
      measured by means of Ling-Gerard microelectrodes in late distal tubule of rat
      renal cortex during in vivo microperfusion. The tubules were perfused with
      electrolyte solutions to which 2 x 10(-7) M bafilomycin or 4.6 x 10(-8) M
      concanamycin were added. No significant increase in lumen-negative Vt upon
      perfusion with these inhibitors as compared to control, was observed as well as
      when 10(-3) m amiloride, 10(-5) M benzamil or 3 mM Ba2+ were perfused alone or in
      combination. The effect of an inhibition of electrogenic H+ secretion, i.e.,
      increase in lumen-negative Vt by 2-4 mV, was observed only when Cl- channels were
      blocked by 10(-5) M 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB). This
      blocker also reduced the rate of bicarbonate reabsorption in this segment from
      1.21 +/- 0.14 (n = 8) to 0.62 +/- 0.03 (8) nmol.cm-2.sec-1 as determined by
      stationary microperfusion and pH measurement by ion-exchange resin
      microelectrodes. These results indicate that: (i) the participation of the
      vacuolar H+ ATPase in the establishment of cortical late distal tubule Vt is
      minor in physiological conditions, but can be demonstrated after blocking Cl-
      channels, thus suggesting a shunting effect of this anion; and, (ii) the rate of
      H+ secretion in this segment is reduced by a Cl- channel blocker, supporting
      coupling of H+-ATPase with Cl- transport.

PMID- 9151661
TI  - Opening of cardiac sarcolemmal KATP channels by dinitrophenol separate from
      metabolic inhibition.
AB  - Opening of ATP-sensitive K+ (KATP) channels by the uncoupler of oxidative
      phosphorylation, 2,4 dinitrophenol (DNP), has been assumed to be secondary to
      metabolic inhibition and reduced intracellular ATP levels. Herein, we present
      data which show that DNP (200 microM) can induce opening of cardiac KATP
      channels, under whole-cell and inside-out conditions, despite millimolar
      concentrations of ATP (1-2. 5 mm). DNP-induced currents had a single channel
      conductance (71 pS), inward rectification, reversal potential, and intraburst
      kinetic properties (open time constant, tauopen: 4.8 msec; fast closed time
      constant, tauclosed(f): 0.33 msec) characteristic of KATP channels suggesting
      that DNP did not affect the pore region of the channel, but may have altered the
      functional coupling of the ATP-dependent channel gating. A DNP analogue, with the
      pH-titrable hydroxyl replaced by a methyl group, could not open KATP channels.
      The pH-dependence of the effect of DNP on channel opening under whole-cell, cell
      attached, and inside-out conditions suggested that transfer of protonated DNP
      across the sarcolemma is essential for activation of KATP channels in the
      presence of ATP. We conclude that the use of DNP for metabolic stress-induced
      KATP channel opening should be reevaluated.

PMID- 9151663
TI  - A proteasome cap subunit required for spindle pole body duplication in yeast.
AB  - Proteasome-mediated protein degradation is a key regulatory mechanism in a
      diversity of complex processes, including the control of cell cycle progression.
      The selection of substrates for degradation clearly depends on the specificity of
      ubiquitination mechanisms, but further regulation may occur within the
      proteasomal 19S cap complexes, which attach to the ends of the 20S proteolytic
      core and are thought to control entry of substrates into the core. We have
      characterized a gene from Saccharomyces cerevisiae that displays extensive
      sequence similarity to members of a family of ATPases that are components of the
      19S complex, including human subunit p42 and S. cerevisiae SUG1/CIM3 and CIM5
      products. This gene, termed PCS1 (for proteasomal cap subunit), is identical to
      the recently described SUG2 gene (Russell, S.J., U.G. Sathyanarayana, and S.A.
      Johnston. 1996. J. Biol. Chem. 271:32810-32817). We have shown that PCS1 function
      is essential for viability. A temperature-sensitive pcs1 strain arrests
      principally in the second cycle after transfer to the restrictive temperature,
      blocking as large-budded cells with a G2 content of unsegregated DNA. EM reveals
      that each arrested pcs1 cell has failed to duplicate its spindle pole body (SPB),
      which becomes enlarged as in other monopolar mutants. Additionally, we have shown
      localization of a functional Pcs1-green fluorescent protein fusion to the nucleus
      throughout the cell cycle. We hypothesize that Pcs1p plays a role in the
      degradation of certain potentially nuclear component(s) in a manner that
      specifically is required for SPB duplication.

PMID- 9151662
TI  - Subnuclear trafficking of glucocorticoid receptors in vitro: chromatin recycling
      and nuclear export.
AB  - We have used digitonin-permeabilized cells to examine in vitro nuclear export of
      glucocorticoid receptors (GRs). In situ biochemical extractions in this system
      revealed a distinct subnuclear compartment, which collects GRs that have been
      released from chromatin and serves as a nuclear export staging area. Unliganded
      nuclear GRs within this compartment are not restricted in their subnuclear
      trafficking as they have the capacity to recycle to chromatin upon rebinding
      hormone. Thus, GRs that release from chromatin do not require transit through the
      cytoplasm to regain functionality. In addition, chromatin-released receptors
      export from nuclei of permeabilized cells in an ATP- and cytosol-independent
      process that is stimulated by sodium molybdate, other group VI-A transition metal
      oxyanions, and some tyrosine phosphatase inhibitors. The stimulation of in vitro
      nuclear export by these compounds is not unique to GR, but is restricted to other
      proteins such as the 70- and 90-kD heat shock proteins, hsp70 and hsp90,
      respectively, and heterogeneous nuclear RNP (hnRNP) A1. Under analogous
      conditions, the 56-kD heat shock protein, hsp56, and hnRNP C do not export from
      nuclei of permeabilized cells. If tyrosine kinase inhibitors genistein and
      tyrphostin AG126 are included to prevent increased tyrosine phosphorylation, in
      vitro nuclear export of GR is inhibited. Thus, our results are consistent with
      the involvement of a phosphotyrosine system in the general regulation of nuclear
      protein export, even for proteins such as GR and hnRNP A1 that use distinct
      nuclear export pathways.

PMID- 9151664
TI  - Multiple determinants direct the orientation of signal-anchor proteins: the
      topogenic role of the hydrophobic signal domain.
AB  - The orientation of signal-anchor proteins in the endoplasmic reticulum membrane
      is largely determined by the charged residues flanking the apolar, membrane
      spanning domain and is influenced by the folding properties of the NH2-terminal
      sequence. However, these features are not generally sufficient to ensure a unique
      topology. The topogenic role of the hydrophobic signal domain was studied in vivo
      by expressing mutants of the asialoglycoprotein receptor subunit H1 in COS-7
      cells. By replacing the 19-residue transmembrane segment of wild-type and mutant
      H1 by stretches of 7-25 leucine residues, we found that the length and
      hydrophobicity of the apolar sequence significantly affected protein orientation.
      Translocation of the NH2 terminus was favored by long, hydrophobic sequences and
      translocation of the COOH terminus by short ones. The topogenic contributions of
      the transmembrane domain, the flanking charges, and a hydrophilic NH2-terminal
      portion were additive. In combination these determinants were sufficient to
      achieve unique membrane insertion in either orientation.

PMID- 9151665
TI  - Two new Ypt GTPases are required for exit from the yeast trans-Golgi compartment.
AB  - Small GTPases of the Ypt/rab family are involved in the regulation of vesicular
      transport. These GTPases apparently function during the targeting of vesicles to
      the acceptor compartment. Two members of the Ypt/rab family, Ypt1p and Sec4p,
      have been shown to regulate early and late steps of the yeast exocytic pathway,
      respectively. Here we tested the role of two newly identified GTPases, Ypt31p and
      Ypt32p. These two proteins share 81% identity and 90% similarity, and belong to
      the same protein subfamily as Ypt1p and Sec4p. Yeast cells can tolerate deletion
      of either the YPT31 or the YPT32 gene, but not both. These observations suggest
      that Ypt31p and Ypt32p perform identical or overlapping functions. Cells deleted
      for the YPT31 gene and carrying a conditional ypt32 mutation exhibit protein
      transport defects in the late exocytic pathway, but not in vacuolar protein
      sorting. The ypt31/ 32 mutant secretory defect is clearly downstream from that
      displayed by a ypt1 mutant and is similar to that of sec4 mutant cells. However,
      electron microscopy revealed that while sec4 mutant cells accumulate secretory
      vesicles, ypt31/32 mutant cells accumulate aberrant Golgi structures. The
      ypt31/32 phenotype is epistatic to that of a sec1 mutant, which accumulates
      secretory vesicles. Together, these results indicate that the Ypt31/32p GTPases
      are required for a step that occurs in the trans-Golgi compartment, between the
      reactions regulated by Ypt1p and Sec4p. This step might involve budding of
      vesicles from the trans-Golgi. Alternatively, Ypt31/32p might promote secretion
      indirectly, by allowing fusion of recycling vesicles with the trans-Golgi
      compartment.

PMID- 9151666
TI  - p53/58 binds COPI and is required for selective transport through the early
      secretory pathway.
AB  - p53/58 is a transmembrane protein that continuously recycles between the ER and
      pre-Golgi intermediates composed of vesicular-tubular clusters (VTCs) found in
      the cell periphery and at the cis face of the Golgi complex. We have generated an
      antibody that uniquely recognizes the p53/58 cytoplasmic tail. Here we present
      evidence that this antibody arrests the anterograde transport of vesicular
      stomatitis virus glycoprotein and leads to the accumulation of p58 in pre-Golgi
      intermediates. Consistent with a role for the KKXX retrieval motif found at the
      cytoplasmic carboxyl terminus of p53/58 in retrograde traffic, inhibition of
      transport through VTCs correlates with the ability of the antibody to block
      recruitment of COPI coats to the p53/58 cytoplasmic tail and to p53/58-containing
      membranes. We suggest that p53/58 function may be required for the coupled
      exchange of COPII for COPI coats during segregation of anterograde and retrograde
      transported proteins.

PMID- 9151668
TI  - Transport of a large oligomeric protein by the cytoplasm to vacuole protein
      targeting pathway.
AB  - Aminopeptidase I (API) is transported into the yeast vacuole by the cytoplasm to
      vacuole targeting (Cvt) pathway. Genetic evidence suggests that autophagy, a
      major degradative pathway in eukaryotes, and the Cvt pathway share largely the
      same cellular machinery. To understand the mechanism of the Cvt import process,
      we examined the native state of API. Dodecameric assembly of precursor API in the
      cytoplasm and membrane binding were rapid events, whereas subsequent vacuolar
      import appeared to be rate limiting. A unique temperature-sensitive API-targeting
      mutant allowed us to kinetically monitor its oligomeric state during
      translocation. Our findings indicate that API is maintained as a dodecamer
      throughout its import and will be useful to study the posttranslational movement
      of folded proteins across biological membranes.

PMID- 9151667
TI  - Differential sorting of lysosomal enzymes out of the regulated secretory pathway
      in pancreatic beta-cells.
AB  - In cells specialized for secretory granule exocytosis, lysosomal hydrolases may
      enter the regulated secretory pathway. Using mouse pancreatic islets and the INS
      1 beta-cell line as models, we have compared the itineraries of procathepsins L
      and B, two closely related members of the papain superfamily known to exhibit low
      and high affinity for mannose-6-phosphate receptors (MPRs), respectively.
      Interestingly, shortly after pulse labeling INS cells, a substantial fraction of
      both proenzymes exhibit regulated exocytosis. After several hours, much
      procathepsin L remains as precursor in a compartment that persists in its ability
      to undergo regulated exocytosis in parallel with insulin, while procathepsin B is
      efficiently converted to the mature form and can no longer be secreted. However,
      in islets from transgenic mice devoid of cation-dependent MPRs, the modest
      fraction of procathepsin B normally remaining within mature secretory granules is
      increased approximately fourfold. In normal mouse islets, immunoelectron
      microscopy established that both cathepsins are present in immature beta
      granules, while immunolabeling for cathepsin L, but not B, persists in mature
      beta-granules. By contrast, in islets from normal male Sprague-Dawley rats, much
      of the proenzyme sorting appears to occur earlier, significantly diminishing the
      stimulus-dependent release of procathepsin B. Evidently, in the context of
      different systems, MPR-mediated sorting of lysosomal proenzymes occurs to a
      variable extent within the trans-Golgi network and is continued, as needed,
      within immature secretory granules. Lysosomal proenzymes that fail to be sorted
      at both sites remain as residents of mature secretory granules.

PMID- 9151669
TI  - Transmembrane domain sequence requirements for activation of the p185c-neu
      receptor tyrosine kinase.
AB  - The receptor tyrosine kinase p185c-neu can be constitutively activated by the
      transmembrane domain mutation Val664-->Glu, found in the oncogenic mutant
      p185neu. This mutation is predicted to allow intermolecular hydrogen bonding and
      receptor dimerization. Understanding the activation of p185c-neu has assumed
      greater relevance with the recent observation that achondroplasia, the most
      common genetic form of human dwarfism, is caused by a similar transmembrane
      domain mutation that activates fibroblast growth factor receptor (FGFR) 3. We
      have isolated novel transforming derivatives of p185c-neu using a large pool of
      degenerate oligonucleotides encoding variants of the transmembrane domain.
      Several of the transforming isolates identified were unusual in that they lacked
      a Glu at residue 664, and others were unique in that they contained multiple Glu
      residues within the transmembrane domain. The Glu residues in the transforming
      isolates often exhibited a spacing of seven residues or occurred in positions
      likely to represent the helical interface. However, the distinction between the
      sequences of the transforming clones and the nontransforming clones did not
      suggest clear rules for predicting which specific sequences would result in
      receptor activation and transformation. To investigate these requirements
      further, entirely novel transmembrane sequences were constructed based on tandem
      repeats of simple heptad sequences. Activation was achieved by transmembrane
      sequences such as [VVVEVVA]n or [VVVEVVV]n, whereas activation was not achieved
      by a transmembrane domain consisting only of Val residues. In the context of
      these transmembrane domains, Glu or Gln were equally activating, while Lys, Ser,
      and Asp were not. Using transmembrane domains with two Glu residues, the spacing
      between these was systematically varied from two to eight residues, with only the
      heptad spacing resulting in receptor activation. These results are discussed in
      the context of activating mutations in the transmembrane domain of FGFR3 that are
      responsible for the human developmental syndromes achondroplasia and acanthosis
      nigricans with Crouzon Syndrome.

PMID- 9151670
TI  - Mitochondrial regulation of store-operated calcium signaling in T lymphocytes.
AB  - Mitochondria act as potent buffers of intracellular Ca2+ in many cells, but a
      more active role in modulating the generation of Ca2+ signals is not well
      established. We have investigated the ability of mitochondria to modulate store
      operated or "capacitative" Ca2+ entry in Jurkat leukemic T cells and human T
      lymphocytes using fluorescence imaging techniques. Depletion of the ER Ca2+ store
      with thapsigargin (TG) activates Ca2+ release-activated Ca2+ (CRAC) channels in T
      cells, and the ensuing influx of Ca2+ loads a TG-insensitive intracellular store
      that by several criteria appears to be mitochondria. Loading of this store is
      prevented by carbonyl cyanide m-chlorophenylhydrazone or by antimycin A1 +
      oligomycin, agents that are known to inhibit mitochondrial Ca2+ import by
      dissipating the mitochondrial membrane potential. Conversely, intracellular Na+
      depletion, which inhibits Na+-dependent Ca2+ export from mitochondria, enhances
      store loading. In addition, we find that rhod-2 labels mitochondria in T cells,
      and it reports changes in Ca2+ levels that are consistent with its localization
      in the TG-insensitive store. Ca2+ uptake by the mitochondrial store is sensitive
      (threshold is <400 nM cytosolic Ca2+), rapid (detectable within 8 s), and does
      not readily saturate. The rate of mitochondrial Ca2+ uptake is sensitive to
      extracellular [Ca2+], indicating that mitochondria sense Ca2+ gradients near CRAC
      channels. Remarkably, mitochondrial uncouplers or Na+ depletion prevent the
      ability of T cells to maintain a high rate of capacitative Ca2+ entry over
      prolonged periods of >10 min. Under these conditions, the rate of Ca2+ influx in
      single cells undergoes abrupt transitions from a high influx to a low influx
      state. These results demonstrate that mitochondria not only buffer the Ca2+ that
      enters T cells via store-operated Ca2+ channels, but also play an active role in
      modulating the rate of capacitative Ca2+ entry.

PMID- 9151671
TI  - Chlamydomonas inner-arm dynein mutant, ida5, has a mutation in an actin-encoding
      gene.
AB  - Chlamydomonas flagellar inner-arm dynein consists of seven subspecies (a-g), of
      which all but f contain actin as subunits. The mutant ida5 and a new strain, ida5
      t, lack four subspecies (a, c, d, and e). These mutants were found to have
      mutations in the conventional actin gene, such that its product is totally lost;
      ida5 has a single-base deletion that results in a stop codon at a position about
      two-thirds from the 5' end of the coding region, and ida5-t lacks a large portion
      of the entire actin gene. Two-dimensional gel electrophoresis patterns of the
      axonemes and inner-arm subspecies b and g of ida5 lacked the spot of actin
      (isoelectric point [pI] = approximately 5.3) but had two novel spots with pIs of
      approximately 5.6 and approximately 5.7 instead. Western blot with different
      kinds of anti-actin antibodies suggested that the proteins responsible for the
      two novel spots and conventional actin are different but share some antigenicity.
      Since Chlamydomonas has been shown to have only a single copy of the conventional
      actin gene, it is likely that the novel spots in ida5 and ida5-t originated from
      another gene(s) that codes for a novel actin-like protein(s) (NAP), which has
      hitherto been undetected in wild-type cells. These mutants retain the two inner
      arm subspecies b and g, in addition to f, possibly because NAP can functionally
      substitute for the actin in these subspecies while they cannot in other
      subspecies. The net growth rate of ida5 and ida5-t cells did not differ from that
      of wild type, but the mating efficiency was greatly reduced. This defect was
      apparently caused by deficient growth of the fertilization tubule. These results
      suggest that NAP can carry out some, but not all, functions performed by
      conventional actin in the cytoplasm and raise the possibility that Chlamydomonas
      can live without ordinary actin.

PMID- 9151672
TI  - An unexpected localization of basonuclin in the centrosome, mitochondria, and
      acrosome of developing spermatids.
AB  - Basonuclin is a zinc finger protein that was thought to be restricted to
      keratinocytes of stratified squamous epithelia. In epidermis, basonuclin is
      associated with the nuclei of mitotically active basal cells but not in
      terminally differentiating keratinocytes. We report here the isolation of a novel
      form of basonuclin, which we show is also expressed in stratified epithelia. Most
      unexpectedly, we find both forms in testis, where a surprising localization
      pattern was uncovered. While basonuclin RNA expression occurs in mitotically
      active germ cells, protein was not detected until the meiotic stage, where
      basonuclin localized to the appendage of the distal centriole of spermatocytes
      and spermatids. Near the end of spermiogenesis, basonuclin also accumulated in
      the acrosome and mitochondrial sheath surrounding the flagellum. Intriguingly, a
      perfect six-amino acid residue mitochondrial targeting sequence (Komiya, T., N.
      Hachiya, M. Sakaguchi, T. Omura, and K. Mihara. 1994. J. Biol. Chem. 269:30893
      30897; Shore, G.C., H.M. McBride, D.G. Millar, N.A. Steenaart, and M. Nguyen.
      1995. Eur. J. Biochem. 227: 9-18; McBride, H.M., I.S. Goping, and G.C. Shore.
      1996. J. Cell. Biol. 134:307-313) is present in basonuclin 1a but not in the 1b
      form. Moreover, three distinct affinity-purified peptide antibodies gave this
      unusual pattern of basonuclin antibody staining, which was confirmed by cell
      fractionation studies. Our findings suggest a unique role for basonuclin in
      centrosomes within the developing spermatid, and a role for one of the protein
      forms in germ cell mitochondrial function. Its localization with the acrosome
      suggests that it may also perform a special function during or shortly after
      fertilization.

PMID- 9151673
TI  - Agrin binds to the nerve-muscle basal lamina via laminin.
AB  - Agrin is a heparan sulfate proteoglycan that is required for the formation and
      maintenance of neuromuscular junctions. During development, agrin is secreted
      from motor neurons to trigger the local aggregation of acetylcholine receptors
      (AChRs) and other proteins in the muscle fiber, which together compose the
      postsynaptic apparatus. After release from the motor neuron, agrin binds to the
      developing muscle basal lamina and remains associated with the synaptic portion
      throughout adulthood. We have recently shown that full-length chick agrin binds
      to a basement membrane-like preparation called Matrigel. The first 130 amino
      acids from the NH2 terminus are necessary for the binding, and they are the
      reason why, on cultured chick myotubes, AChR clusters induced by full-length
      agrin are small. In the current report we show that an NH2-terminal fragment of
      agrin containing these 130 amino acids is sufficient to bind to Matrigel and that
      the binding to this preparation is mediated by laminin-1. The fragment also binds
      to laminin-2 and -4, the predominant laminin isoforms of the muscle fiber basal
      lamina. On cultured myotubes, it colocalizes with laminin and is enriched in AChR
      aggregates. In addition, we show that the effect of full-length agrin on the size
      of AChR clusters is reversed in the presence of the NH2-terminal agrin fragment.
      These data strongly suggest that binding of agrin to laminin provides the basis
      of its localization to synaptic basal lamina and other basement membranes.

PMID- 9151675
TI  - Tyrosine phosphorylation at a site highly conserved in the L1 family of cell
      adhesion molecules abolishes ankyrin binding and increases lateral mobility of
      neurofascin.
AB  - This paper presents evidence that a member of the L1 family of ankyrin-binding
      cell adhesion molecules is a substrate for protein tyrosine kinase(s) and
      phosphatase(s), identifies the highly conserved FIGQY tyrosine in the cytoplasmic
      domain as the principal site of phosphorylation, and demonstrates that
      phosphorylation of the FIGQY tyrosine abolishes ankyrin-binding activity.
      Neurofascin expressed in neuroblastoma cells is subject to tyrosine
      phosphorylation after activation of tyrosine kinases by NGF or bFGF or
      inactivation of tyrosine phosphatases with vanadate or dephostatin. Furthermore,
      both neurofascin and the related molecule Nr-CAM are tyrosine phosphorylated in a
      developmentally regulated pattern in rat brain. The FIGQY sequence is present in
      the cytoplasmic domains of all members of the L1 family of neural cell adhesion
      molecules. Phosphorylation of the FIGQY tyrosine abolishes ankyrin binding, as
      determined by coimmunoprecipitation of endogenous ankyrin and in vitro ankyrin
      binding assays. Measurements of fluorescence recovery after photobleaching
      demonstrate that phosphorylation of the FIGQY tyrosine also increases lateral
      mobility of neurofascin expressed in neuroblastoma cells to the same extent as
      removal of the cytoplasmic domain. Ankyrin binding, therefore, appears to
      regulate the dynamic behavior of neurofascin and is the target for regulation by
      tyrosine phosphorylation in response to external signals. These findings suggest
      that tyrosine phosphorylation at the FIGQY site represents a highly conserved
      mechanism, used by the entire class of L1-related cell adhesion molecules, for
      regulation of ankyrin-dependent connections to the spectrin skeleton.

PMID- 9151674
TI  - The laminin alpha chains: expression, developmental transitions, and chromosomal
      locations of alpha1-5, identification of heterotrimeric laminins 8-11, and
      cloning of a novel alpha3 isoform.
AB  - Laminin trimers composed of alpha, beta, and gamma chains are major components of
      basal laminae (BLs) throughout the body. To date, three alpha chains (alpha1-3)
      have been shown to assemble into at least seven heterotrimers (called laminins 1
      7). Genes encoding two additional alpha chains (alpha4 and alpha5) have been
      cloned, but little is known about their expression, and their protein products
      have not been identified. Here we generated antisera to recombinant alpha4 and
      alpha5 and used them to identify authentic proteins in tissue extracts.
      Immunoprecipitation and immunoblotting showed that alpha4 and alpha5 assemble
      into four novel laminin heterotrimers (laminins 8-11: alpha4beta1gamma1,
      alpha4beta2gamma1, alpha5beta1gamma1, and alpha5beta2gamma1, respectively). Using
      a panel of nucleotide and antibody probes, we surveyed the expression of alpha1-5
      in murine tissues. All five chains were expressed in both embryos and adults, but
      each was distributed in a distinct pattern at both RNA and protein levels.
      Overall, alpha4 and alpha5 exhibited the broadest patterns of expression, while
      expression of alpha1 was the most restricted. Immunohistochemical analysis of
      kidney, lung, and heart showed that the alpha chains were confined to
      extracellular matrix and, with few exceptions, to BLs. All developing and adult
      BLs examined contained at least one alpha chain, all alpha chains were present in
      multiple BLs, and some BLs contained two or three alpha chains. Detailed analysis
      of developing kidney revealed that some individual BLs, including those of the
      tubule and glomerulus, changed in laminin chain composition as they matured,
      expressing up to three different alpha chains and two different beta chains in an
      elaborate and dynamic progression. Interspecific backcross mapping of the five
      alpha chain genes revealed that they are distributed on four mouse chromosomes.
      Finally, we identified a novel full-length alpha3 isoform encoded by the Lama3
      gene, which was previously believed to encode only truncated chains. Together,
      these results reveal remarkable diversity in BL composition and complexity in BL
      development.

PMID- 9151676
TI  - Specific uptake of tumor necrosis factor-alpha is involved in growth control of
      Trypanosoma brucei.
AB  - Trypanosoma brucei is lysed by tumor necrosis factor-alpha (TNF-alpha) in a dose
      dependent way, involving specific binding of the cytokine to a trypanosomal
      glycoprotein present in the flagellar pocket of the parasite. TNF-alpha-gold
      particles are endocytosed via coated pits and vesicles and are directed towards
      lysosome-like digestive organelles. The specific uptake of the cytokine by the
      parasite results in a developmentally regulated loss of osmoregulatory capacity.
      TNF-alpha specific lysis is prevented when lysis assays are performed at a
      temperature <26 degrees C, despite uptake of the cytokine. Inhibition of lysis is
      also observed when a lysosomotropic agent is added during the first 2 h of
      incubation. Both monomorphic and pleomorphic trypanosomes are lysed but only when
      isolated during the peak of parasitaemia. Lysis is not observed with early
      infection stage parasites or procyclic (insect-specific) forms. Anti-TNF-alpha
      treatment of T. brucei-infected mice reveals a dramatic increase in parasitaemia
      in the blood circulation, the spleen, the lymph nodes, and the peritoneal cavity.
      These data suggest that in the mammalian host, TNF-alpha is involved in the
      growth control of T. brucei.

PMID- 9151677
TI  - alpha3beta1 Integrin is required for normal development of the epidermal basement
      membrane.
AB  - Integrins alpha3beta1 and alpha6beta4 are abundant receptors on keratinocytes for
      laminin-5, a major component of the basement membrane between the epidermis and
      the dermis in skin. These integrins are recruited to distinct adhesion structures
      within keratinocytes; alpha6beta4 is present in hemidesmosomes, while alpha3beta1
      is recruited into focal contacts in cultured cells. To determine whether
      differences in localization reflect distinct functions of these integrins in the
      epidermis, we studied skin development in alpha3beta1-deficient mice. Examination
      of extracellular matrix by immunofluorescence microscopy and electron microscopy
      revealed regions of disorganized basement membrane in alpha3beta1-deficient skin.
      Disorganized matrix was first detected by day 15.5 of embryonic development and
      became progressively more extensive as development proceeded. In neonatal skin,
      matrix disorganization was frequently accompanied by blistering at the dermal
      epidermal junction. Laminin-5 and other matrix proteins remained associated with
      both the dermal and epidermal sides of blisters, suggesting rupture of the
      basement membrane itself, rather than detachment of the epidermis from the
      basement membrane as occurs in some blistering disorders such as epidermolysis
      bullosa. Consistent with this notion, primary keratinocytes from alpha3beta1
      deficient skin adhered to laminin-5 through alpha6 integrins. However,
      alpha3beta1-deficient keratinocytes spread poorly compared with wild-type cells
      on laminin-5, demonstrating a postattachment requirement for alpha3beta1 and
      indicating distinct roles for alpha3beta1 and alpha6beta4. Our findings support a
      novel role for alpha3beta1 in establishment and/or maintenance of basement
      membrane integrity, while alpha6beta4 is required for stable adhesion of the
      epidermis to the basement membrane through hemidesmosomes.

PMID- 9151678
TI  - Expression of a P-selectin ligand in zona pellucida of porcine oocytes and P
      selectin on acrosomal membrane of porcine sperm cells. Potential implications for
      their involvement in sperm-egg interactions.
AB  - The selectin family of cell adhesion molecules mediates initial leukocyte
      adhesion to vascular endothelial cells at sites of inflammation. O-glycan
      structural similarities between oligosaccharides from human leukocyte P-selectin
      glycoprotein ligand-1 (PSGL-1) and from zona pellucida glycoproteins of porcine
      oocytes indicate the possible existence of a P-selectin ligand in the zona
      pellucida. Here, using biochemical as well as morphological approaches, we
      demonstrate that a P-selectin ligand is expressed in the porcine zona pellucida.
      In addition, a search for a specific receptor for this ligand leads to the
      identification of P-selectin on the acrosomal membrane of porcine sperm cells. In
      vitro binding of porcine acrosome-reacted sperm cells to oocytes was found to be
      Ca2+ dependent and inhibitable with either P-selectin, P-selectin receptor
      globulin, or leukocyte adhesion blocking antibodies against P-selectin and PSGL
      1. Moreover, porcine sperm cells were found to be capable of binding to human
      promyeloid cell line HL-60. Taken together, our findings implicate a potential
      role for the oocyte P-selectin ligand and the sperm P-selectin in porcine sperm
      egg interactions.

PMID- 9151679
TI  - Tenascin supports lymphocyte rolling.
AB  - Tenascin is a large extracellular matrix molecule expressed at specific sites in
      the adult, including immune system tissues such as the bone marrow, thymus,
      spleen, and T cell areas of lymph nodes. Tenascin has been reported to have both
      adhesive and anti-adhesive effects in static assays. We report here that tenascin
      supports the tethering and rolling of lymphocytes and lymphoblastic cell lines
      under flow conditions. Binding was calcium dependent and was not inhibited by
      treatment of lymphocytes with O-glycoprotease or a panel of glycosidases
      including neuraminidase and heparitinase but was inhibited by treatment of cells
      with proteinase K. Binding was to the fibrinogen-like terminal domain of tenascin
      as determined by antibody blocking studies and binding to recombinant tenascin
      proteins. When compared to rolling of the same cell type on E-selectin, rolling
      on tenascin was found to be smoother at all shear stresses tested, suggesting
      that cells formed a larger number of bonds on the tenascin substrate than on the
      E-selectin substrate. When protein plating densities were adjusted to give
      similar profiles of cell detachment under increasing shears, the density of
      tenascin was 8.5-fold greater than that of E-selectin. Binding to tenascin was
      not dependent on any molecules previously identified as tenascin receptors and is
      likely to involve a novel tenascin receptor on lymphocytes. We postulate that the
      ability of tenascin to support lymphocyte rolling may reflect its ability to
      support cell migration and that this interaction may be used by lymphocytes
      migrating through secondary lymphoid organs.

PMID- 9151680
TI  - Reduction in surface urokinase receptor forces malignant cells into a protracted
      state of dormancy.
AB  - Considerable evidence links urokinase plasminogen activator (uPA) bound to its
      surface receptor (uPAR) with enhanced invasiveness of cancer cells. By blocking
      uPAR expression in human epidermoid carcinoma cells (HEp3), we have now
      identified an additional and novel in vivo function for this receptor by showing
      that receptor-deficient cells enter a state of dormancy reminiscent of that
      observed in human cancer metastasis. Its main characteristic is survival without
      signs of progressive growth. Five clones transfected with a vector expressing
      uPAR antisense RNA under the beta-actin promoter were isolated and shown to have
      uPAR (at the mRNA and protein levels) reduced by 50 to 80%; four clones,
      transfected with vector alone and having uPAR levels similar to those of parental
      cells, served as controls. In confirmation of our previous results, reduced uPAR
      always coincided with a significantly reduced invasiveness. Each of the control
      clones produced rapidly growing, highly metastatic tumors within 2 wk of
      inoculation on chorioallantoic membranes (CAMs) of chick embryos. In contrast,
      each of the clones with low surface uPAR, whose proliferation rate in culture was
      indistinguishable from controls, remained dormant for up to 5 mo when inoculated
      on CAMs. Thus, the reduction in uPAR altered the phenotype of HEp3 tumor cells
      from tumorigenic to dormant. Although protracted, tumor dormancy was not
      permanent since in spite of maintaining low uPAR levels, each of the in vivo
      passaged antisense clones eventually reemerged from dormancy to initiate
      progressive growth and to form metastases at a level of 20 to 90% of that of
      fully malignant control. This observation suggested that other factors, whose
      expression is dependent on cumulative and prolonged in vivo effects, can
      compensate for the lack of a full complement of surface uPAR required for the
      expression of malignant properties. These "reemerged," uPAR-deficient clones were
      easily distinguishable from the vector-transfected controls by the fact that
      after only 1 wk in culture, the invasion of CAM by all five clones and
      tumorigenicity of four of the five clones were reduced back to the values
      observed before in vivo maintenance. In contrast, dissociated and in vitro-grown
      cells of control tumors were fully invasive and produced large, metastatic tumors
      when reinoculated on CAMs. Quantitation of the percent of apoptotic and S-phase
      cells in vivo, in the control and uPAR-deficient, dormant clones, showed that the
      mechanism responsible for the dormancy was a diminished proliferation.

PMID- 9151682
TI  - Deciphering the function of neurexins at cellular junctions.

PMID- 9151681
TI  - Phosphorylation of human pro-urokinase on Ser138/303 impairs its receptor
      dependent ability to promote myelomonocytic adherence and motility.
AB  - Serine phosphorylation of human pro-urokinase (pro-uPA) by A431 human carcinoma
      cells results in a catalytically active molecule with reduced sensitivity to
      plasminogen activator inhibitor type 1. We mapped the phosphorylated seryl
      residues by analyzing the in vivo phosphorylation state of engineered pro-uPA
      variants carrying a COOH-terminal poly-histidine tag. Stably transfected A431
      cells do not incorporate radioactive phosphate into tagged pro-uPA in which the
      serines 138 and 303 have been replaced with glutamic residues, although
      endogenous nontagged pro-uPA is 32P-labeled on A and B chains. Moreover, the
      catalytic-independent ability of the mono- and di-substituted "phosphorylation
      like" variants to bind to the GPI-anchored urokinase receptor (uPAR) and promote
      adherence of differentiating U937, HL-60, and THP-1 myelomonocytic cells was
      examined. We found that glutamic residues as well as the naturally occurring
      phosphoserines at positions 138 and 303 abolish proadhesive ability, although
      they do not interfere with receptor binding. In addition, pro-uPA carrying
      Glu138/303 lacks the capability to induce a chemotactic response of THP-1 cells.
      The exclusive presence of Glu138 reduces pro-uPA proadhesive and chemotactic
      ability by 70-80%, indicating that a phosphoserine residue at the same position
      plays a major inhibitory role of myeloid cell response to pro-urokinase. The di
      substitution does not affect pro-uPA ability to interact with vitronectin or to
      enhance binding of urea-denatured vitronectin to uPAR. However, unlike wild-type
      tagged pro-uPA, the di-substituted variant does not induce receptor polarization
      in pre-adherent U937 cells. Taken together, the data support the possibility that
      pro-uPA phosphorylation on Ser138/303 can modulate uPAR transducing ability.

PMID- 9151683
TI  - A nuclear export signal in Kap95p is required for both recycling the import
      factor and interaction with the nucleoporin GLFG repeat regions of Nup116p and
      Nup100p.
AB  - During nuclear import, cytosolic transport factors move through the nuclear pore
      complex (NPC) to the nuclear compartment. Kap95p is required during import for
      docking the nuclear localization signal-receptor and ligand to the NPC. Recycling
      of this factor back to the cytoplasm is necessary for continued rounds of import;
      however, the mechanism for Kap95p recycling is unknown. We have determined that
      recycling of Kap95p requires a nuclear export signal (NES). A region containing
      the NES in Kap95p was sufficient to mediate active nuclear export in a
      microinjection assay. Moreover, the NES was necessary for function. Mutation of
      the NES in Kap95p resulted in a temperaturesensitive import mutant, and
      immunofluorescence microscopy experiments showed that the mutated Kap95p was not
      recycled but instead localized in the nucleus and at the nuclear envelope. Srp1p,
      the yeast nuclear localization signal-receptor, also accumulated in the nuclei of
      the arrested kap95 mutant cells. Wild-type and NES-mutated Kap95p both bound
      Gsp1p (the yeast Ran/TC4 homologue), Srp1p, and the FXFG repeat region of the
      nucleoporin Nup1p. In contrast, the NES mutation abolished Kap95p interaction
      with the GLFG repeat regions from the nucleoporins Nup116p and Nup100p. In vivo
      interaction was demonstrated by isolation of Kap95p from yeast nuclear lysates in
      either protein A-tagged Nup116p or protein A-tagged Nup100p complexes. The
      protein A-tagged Nup116p complex also specifically contained Gle2p. These results
      support a model in which a step in the recycling of Kap95p is mediated by
      interaction of an NES with GLFG regions. Analysis of genetic interactions
      suggests Nup116p has a primary role in Kap95p recycling, with Nup100p
      compensating in the absence of Nup116p. This finding highlights an important role
      for a subfamily of GLFG nucleoporins in nuclear export processes.

PMID- 9151684
TI  - The Hsp70 homologue Lhs1p is involved in a novel function of the yeast
      endoplasmic reticulum, refolding and stabilization of heat-denatured protein
      aggregates.
AB  - Heat stress is an obvious hazard, and mechanisms to recover from thermal damage,
      largely unknown as of yet, have evolved in all organisms. We have recently shown
      that a marker protein in the ER of Saccharomyces cerevisiae, denatured by
      exposure of cells to 50 degrees C after preconditioning at 37 degrees C, was
      reactivated by an ATP-dependent machinery, when the cells were returned to
      physiological temperature 24 degrees C. Here we show that refolding of the marker
      enzyme Hsp150Delta-beta-lactamase, inactivated and aggregated by the 50 degrees C
      treatment, required a novel ER-located homologue of the Hsp70 family, Lhs1p. In
      the absence of Lhs1p, Hsp150Delta-beta-lactamase failed to be solubilized and
      reactivated and was slowly degraded. Coimmunoprecipitation experiments suggested
      that Lhs1p was somehow associated with heat-denatured Hsp150Delta- beta
      lactamase, whereas no association with native marker protein molecules could be
      detected. Similar findings were obtained for a natural glycoprotein of S.
      cerevisiae, pro-carboxypeptidase Y (pro-CPY). Lhs1p had no significant role in
      folding or secretion of newly synthesized Hsp150Delta-beta-lactamase or pro-CPY,
      suggesting that the machinery repairing heat-damaged proteins may have specific
      features as compared to chaperones assisting de novo folding. After
      preconditioning and 50 degrees C treatment, cells lacking Lhs1p remained capable
      of protein synthesis and secretion for several hours at 24 degrees C, but only
      10% were able to form colonies, as compared to wild-type cells. We suggest that
      Lhs1p is involved in a novel function operating in the yeast ER, refolding and
      stabilization against proteolysis of heatdenatured protein. Lhs1p may be part of
      a fundamental heat-resistant survival machinery needed for recovery of yeast
      cells from severe heat stress.

PMID- 9151685
TI  - An intralysosomal hsp70 is required for a selective pathway of lysosomal protein
      degradation.
AB  - Previous studies have implicated the heat shock cognate (hsc) protein of 73 kD
      (hsc73) in stimulating a lysosomal pathway of proteolysis that is selective for
      particular cytosolic proteins. This pathway is activated by serum deprivation in
      confluent cultured human fibroblasts. We now show, using indirect
      immunofluorescence and laser scanning confocal microscopy, that a heat shock
      protein (hsp) of the 70-kD family (hsp70) is associated with lysosomes (ly
      hsc73). An mAb designated 13D3 specifically recognizes hsc73, and this antibody
      colocalizes with an antibody to lgp120, a lysosomal marker protein. Most, but not
      all, lysosomes contain ly-hsc73, and the morphological appearance of these
      organelles dramatically changes in response to serum withdrawal; the punctate
      lysosomes fuse to form tubules. Based on susceptibility to digestion by trypsin
      and by immunoblot analysis after two-dimensional electrophoresis of isolated
      lysosomes and isolated lysosomal membranes, most ly-hsc73 is within the lysosomal
      lumen. We determined the functional importance of the ly-hsc73 by radiolabeling
      cellular proteins with [3H]leucine and then allowing cells to endocytose excess
      mAb 13D3 before measuring protein degradation in the presence and absence of
      serum. The increased protein degradation in response to serum deprivation was
      completely inhibited by endocytosed mAb 13D3, while protein degradation in cells
      maintained in the presence of serum was unaffected. The intralysosomal digestion
      of endocytosed [3H]RNase A was not affected by the endocytosed mAb 13D3. These
      results suggest that ly-hsc73 is required for a step in the degradative pathway
      before protein digestion within lysosomes, most likely for the import of
      substrate proteins.

PMID- 9151686
TI  - Characterization of the adaptor-related protein complex, AP-3.
AB  - We have recently shown that two proteins related to two of the adaptor subunits
      of clathrincoated vesicles, p47 (mu3) and beta-NAP (beta3B), are part of an
      adaptor-like complex not associated with clathrin (Simpson, F., N.A. Bright, M.A.
      West, L.S. Newman, R.B. Darnell, and M.S. Robinson, 1996. J. Cell Biol. 133:749
      760). In the present study we have searched the EST database and have identified,
      cloned, and sequenced a ubiquitously expressed homologue of beta-NAP, beta3A, as
      well as homologues of the alpha/gamma and sigma adaptor subunits, delta and
      sigma3, which are also ubiquitously expressed. Antibodies raised against
      recombinant delta and sigma3 show that they are the other two subunits of the
      adaptor-like complex. We are calling this complex AP-3, a name that has also been
      used for the neuronalspecific phosphoprotein AP180, but we feel that it is a more
      appropriate designation for an adaptor-related heterotetramer. Immunofluorescence
      using anti-delta antibodies reveals that the AP-3 complex is associated with the
      Golgi region of the cell as well as with more peripheral structures. These
      peripheral structures show only limited colocalization with endosomal markers and
      may correspond to a postTGN biosynthetic compartment. The delta subunit is
      closely related to the protein product of the Drosophila garnet gene, which when
      mutated results in reduced pigmentation of the eyes and other tissues. Because
      pigment granules are believed to be similar to lysosomes, this suggests either
      that the AP-3 complex may be directly involved in trafficking to lysosomes or
      alternatively that it may be involved in another pathway, but that missorting in
      that pathway may indirectly lead to defects in pigment granules.

PMID- 9151687
TI  - Connexin46 is retained as monomers in a trans-Golgi compartment of osteoblastic
      cells.
AB  - Connexins are gap junction proteins that form aqueous channels to interconnect
      adjacent cells. Rat osteoblasts express connexin43 (Cx43), which forms functional
      gap junctions at the cell surface. We have found that ROS 17/2.8 osteosarcoma
      cells, UMR 106-01 osteosarcoma cells, and primary rat calvarial osteoblastic
      cells also express another gap junction protein, Cx46. Cx46 is a major component
      of plasma membrane gap junctions in lens. In contrast, Cx46 expressed by
      osteoblastic cells was predominantly localized to an intracellular perinuclear
      compartment, which appeared to be an aspect of the TGN as determined by
      immunofluorescence colocalization. Hela cells transfected with rat Cx46 cDNA
      (Hela/Cx46) assembled Cx46 into functional gap junction channels at the cell
      surface. Both rat lens and Hela/Cx46 cells expressed 53-kD (nonphosphorylated)
      and 68-kD (phosphorylated) forms of Cx46; however, only the 53-kD form was
      produced by osteoblasts. To examine connexin assembly, monomers were resolved
      from oligomers by sucrose gradient velocity sedimentation analysis of 1% Triton X
      100-solubilized extracts. While Cx43 was assembled into multimeric complexes, ROS
      cells contained only the monomer form of Cx46. In contrast, Cx46 expressed by rat
      lens and Hela/Cx46 cells was assembled into multimers. These studies suggest that
      assembly and cell surface expression of two closely related connexins were
      differentially regulated in the same cell. Furthermore, oligomerization may be
      required for connexin transport from the TGN to the cell surface.

PMID- 9151688
TI  - Coordinated incorporation of skeletal muscle dihydropyridine receptors and
      ryanodine receptors in peripheral couplings of BC3H1 cells.
AB  - Rapid release of calcium from the sarcoplasmic reticulum (SR) of skeletal muscle
      fibers during excitation-contraction (e-c) coupling is initiated by the
      interaction of surface membrane calcium channels (dihydropyridine receptors;
      DHPRs) with the calcium release channels of the SR (ryanodine receptors; RyRs, or
      feet). We studied the early differentiation of calcium release units, which
      mediate this interaction, in BC3H1 cells. Immunofluorescence labelings of
      differentiating myocytes with antibodies against alpha1 and alpha2 subunits of
      DHPRs, RyRs, and triadin show that the skeletal isoforms of all four proteins are
      abundantly expressed upon differentiation, they appear concomitantly, and they
      are colocalized. The transverse tubular system is poorly organized, and thus
      clusters of e-c coupling proteins are predominantly located at the cell
      periphery. Freeze fracture analysis of the surface membrane reveals tetrads of
      large intramembrane particles, arranged in orderly arrays. These appear
      concomitantly with arrays of feet (RyRs) and with the appearance of DHPR/RyS
      clusters, confirming that the four components of the tetrads correspond to
      skeletal muscle DHPRs. The arrangement of tetrads and feet in developing
      junctions indicates that incorporation of DHPRs in junctional domains of the
      surface membrane proceeds gradually and is highly coordinated with the formation
      of RyR arrays. Within the arrays, tetrads are positioned at a spacing of twice
      the distance between the feet. The incorporation of individual DHPRs into tetrads
      occurs exclusively at positions corresponding to alternate feet, suggesting that
      the assembly of RyR arrays not only guides the assembly of tetrads but also
      determines their characteristic spacing in the junction.

PMID- 9151689
TI  - mRNAs for microtubule proteins are specifically colocalized during the sequential
      formation of basal body, flagella, and cytoskeletal microtubules in the
      differentiation of Naegleria gruberi.
AB  - We have examined the distribution of four mRNAs-alpha-tubulin, beta-tubulin,
      flagellar calmodulin, and Class I mRNA-during differentiation of Naegleria
      gruberi amebas into flagellates by in situ hybridization. Three of the four mRNAs
      alpha-tubulin, beta-tubulin, and Class I mRNA-began to be colocalized at the
      periphery of the cells as soon as transcription of the respective genes was
      activated and before any microtubular structures were observable. At 70 min after
      the initiation of differentiation, these mRNAs were relocalized to the base of
      the growing flagella, adjacent to the basal bodies and microtubule organizing
      center for the cytoskeletal microtubules. Within an additional 15 min, the mRNAs
      were translocated to the posterior of the flagellated cells, and by the end of
      differentiation (120 min), very low levels of the mRNAs were observed.
      Cytochalasin D inhibited stage-specific localization of the mRNAs, demonstrating
      that RNA localization was actin dependent. Since cytochalasin D also blocked
      differentiation, this raises the possibility that actin-dependent RNA movement is
      an essential process for differentiation.

PMID- 9151690
TI  - The Drosophila gene abnormal spindle encodes a novel microtubule-associated
      protein that associates with the polar regions of the mitotic spindle.
AB  - abnormal spindle, a gene required for normal spindle structure and function in
      Drosophila melanogaster, lies immediately adjacent the gene tolloid at 96A/B. It
      encodes a 220-kD polypeptide with a predicted pI of 10.8. The recessive mutant
      allele asp1 directs the synthesis of a COOH terminally truncated or internally
      deleted peptide of approximately 124 kD. Wild-type Asp protein copurifies with
      microtubules and is not released by salt concentrations known to dissociate most
      other microtubule-associated proteins. The bacterially expressed NH2-terminal 512
      amino acid peptide, which has a number of potential phosphorylation sites for
      p34(cdc2) and MAP kinases, strongly binds to microtubules. The central 579-amino
      acid segment of the molecule contains one short motif homologous to sequences in
      a number of actin bundling proteins and a second motif present at the calmodulin
      binding sites of several proteins. Immunofluorescence studies show that the wild
      type Asp protein is localized to the polar regions of the spindle immediately
      surrounding the centrosome. These findings are discussed in relation to the known
      spindle abnormalities in asp mutants.

PMID- 9151691
TI  - Dictyostelium IQGAP-related protein specifically involved in the completion of
      cytokinesis.
AB  - The gapA gene encoding a novel RasGTPase-activating protein (RasGAP)-related
      protein was found to be disrupted in a cytokinesis mutant of Dictyostelium that
      grows as giant and multinucleate cells in a dish culture. The predicted sequence
      of the GAPA protein showed considerable homology to those of Gap1/Sar1 from
      fission yeast and the COOH-terminal half of mammalian IQGAPs, the similarity
      extending beyond the RasGAP-related domain. In suspension culture, gapA- cells
      showed normal growth in terms of the increase in cell mass, but cytokinesis
      inefficiently occurred to produce spherical giant cells. Time-lapse recording of
      the dynamics of cell division in a dish culture revealed that, in the case of
      gapA- cells, cytokinesis was very frequently reversed at the step in which the
      midbody connecting the daughter cells should be severed. Earlier steps of
      cytokinesis in the gapA- cells seemed to be normal, since myosin II was
      accumulated at the cleavage furrow. Upon starvation, gapA- cells developed and
      formed fruiting bodies with viable spores, like the wild-type cells. These
      results indicate that the GAPA protein is specifically involved in the completion
      of cytokinesis. Recently, it was reported that IQGAPs are putative effectors for
      Rac and CDC42, members of the Rho family of GTPases, and participate in
      reorganization of the actin cytoskeleton. Thus, it is possible that Dictyostelium
      GAPA participates in the severing of the midbody by regulating the actin
      cytoskeleton through an interaction with a member of small GTPases.

PMID- 9151693
TI  - Androgen ablation leads to an upregulation and intranuclear accumulation of
      deoxyribonuclease I in rat prostate epithelial cells paralleling their apoptotic
      elimination.
AB  - After androgen ablation by castration, the epithelial cells of the rat ventral
      prostate are eliminated by apoptosis. The number of cells showing apoptotic
      chromatin degradation increases with time up to day 3 after castration as
      verified by in situ end labeling of fragmented DNA. Apoptotic chromatin
      degradation is catalyzed by a Ca2+, Mg2+-dependent endonuclease. Recently,
      evidence has been presented that suggests deoxyribonuclease I (DNase I) is
      identical or very closely related to the apoptotic endonuclease (Peitsch, M.C.,
      B. Polzar, H. Stephan, T. Crompton, H.R. MacDonald, H.G. Mannherz, and J.
      Tschopp. 1993. EMBO [Eur. Mol. Biol. Organ.] J. 12:371-377). Therefore, the
      expression of DNase I in the ventral prostate of the rat was analyzed before and
      after androgen ablation at the level of protein, enzymatic activity, and gene
      transcripts using immunohistochemical and biochemical techniques. DNase I
      immunoreactivity was detected only in a few single epithelial cells before
      androgen ablation. After castration, a time-dependent increase in DNase I
      immunoreactivity was observed within the epithelial cells. It first appeared
      after about 12 h in the apical region of a large number of epithelial cells. Up
      to day 3 after castration, the intracellular DNase I antigenicity continuously
      increased, and the cell nuclei gradually became DNase I positive. At day 5,
      almost all nuclei of the epithelium were stained by anti-DNase I. DNase I
      immunoreactivity was particularly concentrated in cells showing morphological
      signs of apoptosis, like nuclear fragmentation, and in many cases was found to
      persist in apoptotic bodies. DNase I gene transcripts were detected in control
      animals using dot and Northern blotting as well as RNase protection assay. After
      androgen ablation, the amount of DNase I gene transcripts in total extractable
      RNA was found unchanged or only slightly decreased up to day 5. Their exclusive
      localization within the epithelial cells was verified by in situ hybridization.
      Before castration, the DNase I gene transcripts were homogeneously distributed in
      all epithelial cells. At day 3, DNase I-specific mRNA was found to be highly
      concentrated in cells of apoptotic morphology. Using the zymogram technique, a
      single endonucleolytic activity of about 32 kD was detected in tissue homogenates
      before castration. After androgen ablation, the endonucleolytic activity
      increased about four- to sevenfold up to day 3. At day 5, however, it had dropped
      to its original level. At day 1, three new endonucleolytic variants of higher
      molecular mass were expressed. At day 3, the predominant endonucleolytic activity
      exhibited an apparent molecular mass of 32 kD. Enzymatic analysis of the
      endonucleases present in prostate homogenates before and after castration
      demonstrated properties identical to DNase I. They were inhibited by chelators of
      divalent cations, Zn2+ ions and monomeric actin. Immunodepletion was achieved by
      immobilized antibodies specific for rat parotid DNase I. A polyclonal antibody
      raised against denatured DNase I was shown by Western blotting to stain a 32-kD
      band after enrichment of the endonuclease from day 0 and 3 homogenates by
      preparative gel electrophoresis. The data thus indicate that androgen ablation
      leads to translational upregulation of an endonucleolytic activity with
      properties identical to DNase I in rat ventral prostate, followed by its
      intracellular retention and final nuclear translocation in those epithelial cells
      that are destined to apoptotic elimination.

PMID- 9151692
TI  - A glycine-rich RNA-binding protein mediating cold-inducible suppression of
      mammalian cell growth.
AB  - In response to low ambient temperature, mammalian cells as well as microorganisms
      change various physiological functions, but the molecular mechanisms underlying
      these adaptations are just beginning to be understood. We report here the
      isolation of a mouse cold-inducible RNA-binding protein (cirp) cDNA and
      investigation of its role in cold-stress response of mammalian cells. The cirp
      cDNA encoded an 18-kD protein consisting of an amino-terminal RNAbinding domain
      and a carboxyl-terminal glycine-rich domain and exhibited structural similarity
      to a class of stress-induced RNA-binding proteins found in plants.
      Immunofluorescence microscopy showed that CIRP was localized in the nucleoplasm
      of BALB/3T3 mouse fibroblasts. When the culture temperature was lowered from 37
      to 32 degrees C, expression of CIRP was induced and growth of BALB/3T3 cells was
      impaired as compared with that at 37 degrees C. By suppressing the induction of
      CIRP with antisense oligodeoxynucleotides, this impairment was alleviated, while
      overexpression of CIRP resulted in impaired growth at 37 degrees C with
      prolongation of G1 phase of the cell cycle. These results indicate that CIRP
      plays an essential role in cold-induced growth suppression of mouse fibroblasts.
      Identification of CIRP may provide a clue to the regulatory mechanisms of cold
      responses in mammalian cells.

PMID- 9151694
TI  - Identification of a novel marker for primordial smooth muscle and its
      differential expression pattern in contractile vs noncontractile cells.
AB  - The assembly of the vessel wall from its cellular and extracellular matrix
      components is an essential event in embryogenesis. Recently, we used the
      descending aorta of the embryonic quail to define the morphological events that
      initiate the formation of a multilayered vessel wall from a nascent endothelial
      cell tube (Hungerford, J.E., G.K. Owens, W.S. Argraves, and C.D. Little. 1996.
      Dev. Biol. 178:375-392). We generated an mAb, 1E12, that specifically labels
      smooth muscle cells from the early stages of development to adulthood. The goal
      of our present study was to characterize further the 1E12 antigen using both
      cytological and biochemical methods. The 1E12 antigen colocalizes with the actin
      cytoskeleton in smooth muscle cells grown on planar substrates in vitro; in
      contrast, embryonic vascular smooth muscle cells in situ contain 1E12 antigen
      that is distributed in threadlike filaments and in cytoplasmic rosette-like
      patterns. Initial biochemical analysis shows that the 1E12 mAb recognizes a
      protein, Mr = 100,000, in lysates of adult avian gizzard. An additional
      polypeptide band, Mr = 40,000, is also recognized in preparations of lysate, when
      stronger extraction conditions are used. We have identified the 100-kD
      polypeptide as smooth muscle alpha-actinin by tandem mass spectroscopy analysis.
      The 1E12 antibody is an IgM isotype. To prepare a more convenient 1E12
      immunoreagent, we constructed a single chain antibody (sFv) using recombinant
      protein technology. The sFv recognizes a single 100-kD protein in gizzard
      lysates. Additionally, the recombinant antibody recognizes purified smooth muscle
      alpha-actinin. Our results suggest that the 1E12 antigen is a member of the alpha
      actinin family of cytoskeletal proteins; furthermore, the onset of its expression
      defines a primordial cell restricted to the smooth muscle lineage.

PMID- 9151695
TI  - Carcinoembryonic antigen, a human tumor marker, cooperates with Myc and Bcl-2 in
      cellular transformation.
AB  - Carcinoembryonic antigen (CEA) is a tumor marker that is overexpressed in many
      human cancers and functions in vitro as a homotypic intercellular adhesion
      molecule. We have investigated the possibility of synergy between CEA, v-Myc, and
      Bcl-2 in the transformation of cells with differentiation capacity. We find that
      v-Myc increases the cell division rate and maximum density of rat L6 myoblasts
      but also markedly stimulates both apoptosis and surprisingly, differentiation,
      thus preventing transformation. The superposition of Bcl-2 blocks the apoptotic
      stimulation of v-Myc and independently promotes further cell division at
      confluence, but still allows differentiation. The further expression of CEA has a
      dominant effect in blocking differentiation, regardless of the presence of the
      other activated oncogenes, generating cells that enter a reversible quiescent G0
      like state in medium promoting differentiation. Transfectants expressing CEA with
      or without v-myc and bcl-2 allow the emergence of cells with the property of
      heritable, efficient, anchorage-independent growth in soft agar and the ability
      to markedly reduce the latency for tumor formation in nude mice. We propose that
      by prolonging cell survival in the presence of differentiation signals, CEA
      represents a novel class of dominant differentiation-blocking oncogene.

PMID- 9151696
TI  - Polyoma middle T-induced vascular tumor formation: the role of the plasminogen
      activator/plasmin system.
AB  - The middle T antigen of murine Polyomavirus (PymT) rapidly transforms endothelial
      cells, leading to the formation of vascular tumors in newborn mice. Transformed
      endothelial (End.) cell lines established from such tumors exhibit altered
      proteolytic activity as a result of increased expression of urokinase-type
      plasminogen activator (uPA) and are capable of inducing vascular tumors
      efficiently when injected into adult mice. In this study we have used mice
      lacking components of the PA/plasmin system to analyze the role of this system in
      the transformation process and in tumor growth. We found that the proteolytic
      status of the host is not a critical determinant for PymT-induced vascular tumor
      formation. In addition, the lack of either uPA or tissue-type PA (tPA) activity
      is not limiting for the establishment and proliferation of End. cells in vitro,
      although the combined loss of both PA activities leads to a marked reduction in
      proliferation rates. Furthermore, the in vitro morphogenetic properties of mutant
      End. cells in fibrin gels could only be correlated with an altered proteolytic
      status in cells lacking both uPA and tPA. However, in contrast with tumors
      induced by PymT itself, the tumorigenic potential of mutant and wild-type End.
      cell lines was found to be highly dependent on the proteolytic status of both the
      tumor cells and the host. Thus, genetic alterations in the PA/plasmin system
      affect vascular tumor development, indicating that this system is a causal
      component in PymTmediated oncogenesis.

PMID- 9151697
TI  - Regulatory T cells specific for the same framework 3 region of the Vbeta8.2 chain
      are involved in the control of collagen II-induced arthritis and experimental
      autoimmune encephalomyelitis.
AB  - Recent evidence indicates that chronic autoimmune disease can result from
      breakdown of regulation and subsequent activation of self-reactive T cells. In
      many murine autoimmune disease systems and in the Lewis rat, antigen-specific T
      cells utilizing the T cell receptor (TCR) Vbeta8.2 gene segment play a major
      role. In the myelin basic protein-induced experimental autoimmune
      encephalomyelitis (EAE) model in H-2(u) mice, we had shown that T cells
      recognizing a peptide determinant within the framework 3 region of the Vbeta8.2
      chain have a critical role in influencing the course of the disease. Here, we
      report experiments in another disease system, collagen II (CII)-induced arthritis
      (CIA) in DBA/1LacJ (H-2(q)) mice, indicating a remarkably parallel control
      circuit to that found for EAE. A critical role is played by CII-specific Vbeta8.2
      bearing T cells in the CIA system, which we have confirmed. Animals treated with
      the superantigen SEB before CII administration are significantly protected from
      CIA. Next, we tested the ability of peptides encompassing the entire Vbeta8.2
      chain to induce proliferative responses. Only TCR peptide B5 (amino acids 76
      101), a regulatory peptide in EAE, induced proliferation. B5 was then used to
      vaccinate DBA/1LacJ mice and was shown to reduce greatly the severity and
      incidence of CIA as measured by joint inflammation or histology. Furthermore,
      similar protection was found when B5 was administered after CII immunization. It
      was shown that there is physiological induction of a proliferative response to B5
      during CIA and that the determinant within B5 is produced from a single chain TCR
      construct containing the entire Vbeta8.2 chain. Finally, the regulation of CIA is
      discussed in the context of other experimental autoimmune diseases, especially
      EAE, with emphasis on what appear to be strikingly common mechanisms.

PMID- 9151698
TI  - Preferential interaction of a novel tumor surface protein (p38.5) with naive
      natural killer cells.
AB  - A receptor-ligand interaction exclusive to natural killer (NK) cell-mediated
      recognition and triggering of tumor cell destruction has not yet been identified.
      In contrast, molecules that are involved in cellular adhesion and regulation of
      NK cytolysis have been well studied. In this report, a novel tumor surface
      protein is identified that exhibits characteristics of a recognition structure
      for naive NK cells. A tagged ligand-cell adsorption technique revealed a 38.5-kD
      plasma membrane protein (p38.5) from a prototypical NK-susceptible cell line
      (K562) that preferentially bound to NK cells (CD3(-)CD5(-)CD16(+)) relative to T
      lymphocytes (CD3(+)CD5(+) CD16(-)). The molecule was purified to apparent
      homogeneity for further characterization. An amino acid sequence of an 11-mer
      internal peptide of p38.5 did not exhibit homology to known proteins. Affinity
      purified antibody generated against this peptide (anti-p38.5) reacted with a
      single protein of 38.5 kD on Western blots of whole cell extracts of K562. Flow
      cytometry and immunoprecipitation studies of surface-labeled tumor cells
      demonstrated expression of p38.5 on NK-susceptible tumor cell lines (K562, MOLT
      4, Jurkat), whereas p38.5 was not detected on NK-resistant tumor cell lines
      (A549, Raji, MDA-MB-231). Significantly, p38.5 loss variants derived from wild
      type Jurkat and Molt-4 cell lines exhibited decreased susceptibility to NK cell
      mediated lysis demonstrating a strong association between cell surface expression
      of p38.5 and cytotoxicity. Purified p38.5 retained preferential binding to NK
      cells and inhibited NK activity in a dose-dependent manner, thereby providing
      direct evidence of a role in the lytic process. Binding studies identified a 70
      kD membrane protein from NK cells as a possible receptor for the p38.5 tumor
      ligand. Consistent with cellular adsorption studies, the 70-kD, p38.5 binding
      protein was not detected on T lymphocytes. Based on studies demonstrating
      selective binding of p38.5 to NK cells, lack of expression on NK-resistant tumor
      cell lines and ability of the purified molecule to block cytolysis, we conclude
      that p38.5 may serve as a recognition/triggering ligand for naive human NK cells.

PMID- 9151699
TI  - A novel inhibitory receptor (ILT3) expressed on monocytes, macrophages, and
      dendritic cells involved in antigen processing.
AB  - Immunoglobulin-like transcript (ILT) 3 is a novel cell surface molecule of the
      immunoglobulin superfamily, which is selectively expressed by myeloid antigen
      presenting cells (APCs) such as monocytes, macrophages, and dendritic cells. The
      cytoplasmic region of ILT3 contains putative immunoreceptor tyrosine-based
      inhibitory motifs that suggest an inhibitory function of ILT3. Indeed, co
      ligation of ILT3 to stimulatory receptors expressed by APCs results in a dramatic
      blunting of the increased [Ca2+]i and tyrosine phosphorylation triggered by these
      receptors. Signal extinction involves SH2-containing protein tyrosine phosphatase
      1, which is recruited by ILT3 upon cross-linking. ILT3 can also function in
      antigen capture and presentation. It is efficiently internalized upon cross
      linking, and delivers its ligand to an intracellular compartment where it is
      processed and presented to T cells. Thus, ILT3 is a novel inhibitory receptor
      that can negatively regulate activation of APCs and can be used by APCs for
      antigen uptake.

PMID- 9151700
TI  - The immunoglobulin (Ig)alpha and Igbeta cytoplasmic domains are independently
      sufficient to signal B cell maturation and activation in transgenic mice.
AB  - The B cell antigen receptor, composed of membrane immunoglobulin (Ig) sheathed by
      the Igalpha/Igbeta heterodimer plays a critical role in mediating B cell
      development and responses to antigen. The cytoplasmic tails of Igalpha and Igbeta
      differ substantially but have been well conserved in evolution. Transfection
      experiments have revealed that, while these tails share an esssential tyrosine
      based activation motif (ITAM), they perform differently in some but not all
      assays and have been proposed to recruit distinct downstream effectors. We have
      created transgenic mouse lines expressing chimeric receptors comprising an IgM
      fused to the cytoplasmic domain of each of the sheath polypeptides. IgM/alpha and
      IgM/beta chimeras (but not an IgM/beta with mutant ITAM) are each independently
      sufficient to mediate allelic exclusion, rescue B cell development in gene
      targeted Igmu- mice that lack endogenous antigen receptors, as well as signal for
      B7 upregulation. While the (IgM/alpha) x (IgM/beta) double-transgenic mouse
      revealed somewhat more efficient allelic exclusion, our data indicate that each
      of the sheath polypeptides is sufficient to mediate many of the essential
      functions of the B cell antigen receptor, even if the combination gives optimal
      activity.

PMID- 9151701
TI  - Spermine inhibits proinflammatory cytokine synthesis in human mononuclear cells:
      a counterregulatory mechanism that restrains the immune response.
AB  - The local production of proinflammatory cytokines mediates the host response to
      inflammation, infection, and injury, whereas an overexpression of these mediators
      can injure or kill the host. Recently, we identified a class of multivalent
      guanylhydrazone compounds that are effective inhibitors of proinflammatory
      cytokine synthesis in monocytes/macrophages. The structure of one such cationic
      molecule suggested a molecular mimicry with spermine, a ubiquitous endogenous
      biogenic amine that increases significantly at sites of inflammation and
      infection. Here, we addressed the hypothesis that spermine might counterregulate
      the innate immune response by downregulating the synthesis of potentially
      injurious cytokines. When spermine was added to cultures of human peripheral
      blood mononuclear cells stimulated with lipopolysaccharide (LPS), it effectively
      inhibited the synthesis of the proinflammatory cytokines tumor necrosis factor
      (TNF), interleukin-1 (IL-1), IL-6, MIP-1alpha, and MIP-1beta. The inhibition of
      cytokine synthesis was specific and reversible, with significant inhibition of
      TNF synthesis occurring even when spermine was added after LPS. The mechanism of
      spermine-mediated cytokine suppression was posttranscriptional and independent of
      polyamine oxidase activity. Local administration of spermine in vivo protected
      mice against the development of acute footpad inflammation induced by
      carrageenan. These results identify a distinct molecular counterregulatory role
      for spermine in downregulating the monocyte proinflammatory cytokine response.

PMID- 9151702
TI  - Transforming growth factor beta (TGF-beta)-dependent inhibition of T helper cell
      2 (Th2)-induced autoimmunity by self-major histocompatibility complex (MHC) class
      II-specific, regulatory CD4(+) T cell lines.
AB  - Autoreactive anti-MHC class II T cells are found in Brown Norway (BN) and Lewis
      (LEW) rats that receive either HgCl2 or gold salts. These T cells have a T helper
      cell 2 (Th2) phenotype in the former strain and are responsible for Th2-mediated
      autoimmunity. In contrast, T cells that expand in LEW rats produce IL-2 and
      prevent experimental autoimmune encephalomyelitis, a cell-mediated autoimmune
      disease. The aim of this work was to investigate, using T cell lines derived from
      HgCl2-injected LEW rats (LEWHg), the effect of these autoreactive T cells on the
      development of Th2-mediated autoimmunity. The five LEWHg T cell lines obtained
      protect against Th2-mediated autoimmunity induced by HgCl2 in (LEW x BN)F1
      hybrids. The lines produce, in addition to IL-2, IFN-gamma and TGF-beta, and the
      protective effect is TGF-beta dependent since protection is abrogated by anti-TGF
      beta treatment. These results identify regulatory, TGF-beta-producing,
      autoreactive T cells that are distinct from classical Th1 or Th2 and inhibit both
      Th1- and Th2-mediated autoimmune diseases.

PMID- 9151703
TI  - A regulatory role for TRAF1 in antigen-induced apoptosis of T cells.
AB  - Tumor necrosis factor receptor (TNFR)-associated factor 2 (TRAF2) and TRAF1 were
      found as components of the TNFR2 signaling complex, which exerts multiple
      biological effects on cells such as cell proliferation, cytokine production, and
      cell death. In the TNFR2-mediated signaling pathways, TRAF2 works as a mediator
      for activation signals such as NF-kappaB, but the role of TRAF1 has not been
      previously determined. Here we show in transgenic mice that TRAF1 overexpression
      inhibits antigen-induced apoptosis of CD8(+) T lymphocytes. Our results
      demonstrate a biological role for TRAF1 as a regulator of apoptotic signals and
      also support the hypothesis that the combination of TRAF proteins in a given cell
      type determines distinct biological effects triggered by members of the TNF
      receptor superfamily.

PMID- 9151704
TI  - Role of repetitive antigen patterns for induction of antibodies against
      antibodies.
AB  - Antibody responses against antibodies, such as rheumatoid factors, are found in
      several immunopathological diseases and may play a role in disease pathogenesis.
      Experience shows that they are usually difficult to induce experimentally.
      Antibodies specific for immunoglobulin constant regions (anti-allotypic) or for
      variable regions (anti-idiotypic) have been investigated in animal models; the
      latter have even been postulated to regulate antibody and T cell responses via
      network-like interactions. Why and how such anti-antibodies are induced during
      autoimmune diseases, has remained largely unclear. Because repetitively arranged
      epitopes in a paracrystalline structure of a viral envelope cross-link B cell
      receptors efficiently to induce a prompt T-independent IgM response, this study
      used immune complexes containing viruses or bacteria to evaluate the role of
      antigen pattern for induction of anti-antibody responses. We present evidence
      that antibodies bound to strictly ordered, but not to irregularly arranged,
      antigens dramatically enhance induction of anti-antibodies, already after a
      single immunization and without using adjuvants. The results indicate a novel
      link between anti-antibody responses and infectious agents, and suggest a similar
      role for repetitive self-antigens such as DNA or collagen involved in chronic
      immunopathological diseases.

PMID- 9151705
TI  - Identification of an epitope on the Entamoeba histolytica 170-kD lectin
      conferring antibody-mediated protection against invasive amebiasis.
AB  - The emergence of multidrug-resistant organisms and the failure to eradicate
      infection by a number of important pathogens has led to increased efforts to
      develop vaccines to prevent infectious diseases. However, the nature of the
      immune response to vaccination with a given antigen can be complex and
      unpredictable. An example is the galactose- and N-acetylgalactosamine-inhibitable
      lectin, a surface antigen of Entamoeba histolytica that has been identified as a
      major candidate in a vaccine to prevent amebiasis. Vaccination with the lectin
      can induce protective immunity to amebic liver abscess in some animals, but
      others of the same species exhibit exacerbations of disease after vaccination. To
      better understand this phenomenon, we used recombinant proteins corresponding to
      four distinct domains of the molecule, and synthetic peptides to localize both
      protective and exacerbative epitopes of the heavy chain subunit of the lectin. We
      show that protective immunity after vaccination can be correlated with the
      development of an antibody response to a region of 25 amino acid residues of the
      lectin, and have confirmed the importance of the antibody response to this region
      by passive immunization studies. In addition, we show that exacerbation of
      disease can be linked to the development of antibodies that bind to an NH2
      terminal domain of the lectin. These findings are clinically relevant, as
      individuals who are colonized with E. histolytica but are resistant to invasive
      disease have a high prevalence of antibodies to the protective epitope(s),
      compared to individuals with a history of invasive amebiasis. These studies
      should enable us to develop an improved vaccine for amebiasis, and provide a
      model for the identification of protective and exacerbative epitopes of complex
      antigens.

PMID- 9151706
TI  - Altered hapten ligands antagonize trinitrophenyl-specific cytotoxic T cells and
      block internalization of hapten-specific receptors.
AB  - Low molecular chemicals (haptens) frequently cause T cell-mediated adverse immune
      reactions. Our previous work provided evidence that hapten-specific T cells, in
      analogy to those specific for nominal peptide antigens, direct their TCR towards
      hapten-modified, MHC-associated peptides. We now demonstrate that trinitrophenyl
      (TNP)-specific, class I MHC-restricted CTL from mice may exhibit exquisite
      specificity for subtle structural details of these hapten determinants,
      surpassing even the specificity of immunoglobulins. More importantly, these CTL
      could be antagonized by ligands altered either in their peptide sequence or in
      their hapten structure. The system was employed to examine the molecular basis of
      T cell antagonism. Whereas agonists resulted in a dose-dependent downregulation
      of TCR in different mouse T cell clones, antagonistic peptides totally failed to
      do so despite engaging the specific TCR. Moreover, simultaneous presentation of
      antagonist and agonist on the same antigen presenting cell prevented TCR
      internalization. No signs of anergy or functional receptor inactivation were
      observed in CTL treated with antagonist-loaded target cells. Based on a serial
      triggering model of T cell activation, our data favor a model in which
      antagonists block T cell functions by competitively engaging the specific TCR in
      unproductive interactions.

PMID- 9151707
TI  - Kinetics and extent of T cell activation as measured with the calcium signal.
AB  - We have characterized the calcium response of a peptide-major histocompatibility
      complex (MHC)-specific CD4(+) T lymphocyte line at the single cell level using a
      variety of ligands, alone and in combination. We are able to distinguish four
      general patterns of intracellular calcium elevation, with only the most robust
      correlating with T cell proliferation. Whereas all three antagonist peptides
      tested reduce the calcium response to an agonist ligand, two give very different
      calcium release patterns and the third gives none at all, arguing that (a)
      antagonism does not require calcium release and (b) it involves interactions that
      are more T cell receptor proximal. We have also measured the time between the
      first T cell-antigen-presenting cell contact and the onset of the calcium signal.
      The duration of this delay correlates with the strength of the stimulus, with
      stronger stimuli giving a more rapid response. The dose dependence of this delay
      suggests that the rate-limiting step in triggering the calcium response is not
      the clustering of peptide-MHC complexes on the cell surface but more likely
      involves the accumulation of some intracellular molecule or complex with a half
      life of a few minutes.

PMID- 9151708
TI  - A new mouse gene, SRG3, related to the SWI3 of Saccharomyces cerevisiae, is
      required for apoptosis induced by glucocorticoids in a thymoma cell line.
AB  - We isolated a new mouse gene that is highly expressed in thymocytes, testis, and
      brain. This gene, SRG3, showed a significant sequence homology to SWI3, a yeast
      transcriptional activator, and its human homolog BAF155. SRG3 encodes 1,100 amino
      acids and has 33-47% identity with SWI3 protein over three regions. The SRG3
      protein contains an acidic NH2 terminus, a myb-like DNA binding domain, a leucine
      zipper motif, and a proline- and glutamine-rich region at its COOH terminus.
      Rabbit antiserum raised against a COOH-terminal polypeptide of the SRG3
      recognized a protein with an apparent molecular mass of 155 kD. The serum also
      detected a 170-kD protein that seems to be a mouse homologue of human BAF170.
      Immunoprecipitation of cell extract with the antiserum against the mouse SRG3
      also brought down a 195-kD protein that could be recognized by an antiserum
      raised against human SWI2 protein. The results suggest that the SRG3 protein
      associates with a mouse SWI2. The SRG3 protein is expressed about three times
      higher in thymocytes than in peripheral lymphocytes. The expression of anti-sense
      RNA to SRG3 mRNA in a thymoma cell line, S49.1, reduced the expression level of
      the SRG3 protein, and decreased the apoptotic cell death induced by
      glucocorticoids. These results suggest that the SRG3 protein is involved in the
      glucocorticoid-induced apoptosis in the thymoma cell line. This implicates that
      the SRG3 may play an important regulatory role during T cell development in
      thymus.

PMID- 9151709
TI  - Unequal death in T helper cell (Th)1 and Th2 effectors: Th1, but not Th2,
      effectors undergo rapid Fas/FasL-mediated apoptosis.
AB  - T helper cell (Th) 1, but not Th2, effectors undergo rapid Fas/Fas ligand (FasL)
      mediated, activation-induced cell death upon restimulation with antigen. Unequal
      apoptosis is also observed without restimulation, after a longer lag period. Both
      effectors undergo delayed apoptosis induced by a non-Fas-mediated pathway. When
      Th1 and Th2 effectors are co-cultured, Th2 effectors survive preferentially,
      suggesting the responsible factor(s) is intrinsic to each population. Both Th1
      and Th2 effectors express Fas and FasL, but only Th2 effectors express high
      levels of FAP-1, a Fas-associated phosphatase that may act to inhibit Fas
      signaling. The rapid death of Th1 effectors leading to selective Th2 survival
      provides a novel mechanism for differential regulation of the two subsets.

PMID- 9151710
TI  - Galectin-1, an endogenous lectin produced by thymic epithelial cells, induces
      apoptosis of human thymocytes.
AB  - Galectin-1, a beta-galactoside binding protein, is produced by thymic epithelial
      cells and binds to human thymocytes. We have previously reported that galectin-1
      induces the apoptosis of activated T lymphocytes. Because the majority of
      thymocytes die via apoptosis while still within the thymus, we tested whether
      galectin-1 could induce the apoptosis of these cells. We now report that in vitro
      exposure to galectin-1 induced apoptosis of two subsets of CD4(lo) CD8(lo)
      thymocytes. The phenotypes of susceptible thymocytes were consistent with that of
      both negatively selected and nonselected cells. Galectin-1-induced apoptosis was
      enhanced by preexposure of thymocytes to antibody to CD3, suggesting that
      galectin-1 may be a participant in T-cell- receptor mediated apoptosis. In
      contrast, pretreatment of thymocytes with dexamethasone had no effect on galectin
      1 susceptibility. We noted that 71% of the cells undergoing apoptosis after
      galectin-1 treatment had a DNA content greater than 2N, indicating that
      proliferating thymocytes were most sensitive to galectin-1. We propose that
      galectin-1 plays a role in the apoptosis of both negatively selected and
      nonselected thymocytes, and that the susceptibility of thymocytes to galectin-1
      is regulated, in part, by entry or exit from the cell cycle.

PMID- 9151711
TI  - Degradation of T cell receptor (TCR)-CD3-zeta complexes after antigenic
      stimulation.
AB  - T cell activation by specific antigen results in a rapid and long-lasting
      downregulation of triggered T cell receptors (TCRs). In this work, we
      investigated the fate of downregulated TCR- CD3-zeta complexes. T cells
      stimulated by peptide-pulsed antigen-presenting cells (APCs) undergo an antigen
      dose-dependent decrease of the total cellular content of TCR-beta, CD3-epsilon,
      and zeta chains, as detected by FACS(R) analysis on fixed and permeabilized T-APC
      conjugates and by Western blot analysis on cell lysates. The time course of CD3
      zeta chain consumption overlaps with that of TCR downregulation, indicating that
      internalized TCR-CD3 complexes are promptly degraded. Inhibitors of lysosomal
      function (bafilomycin A1, folimycin) markedly reduced zeta chain degradation,
      leading to the accumulation of zeta chain in large Lamp1(+) vesicles. These
      results indicate that in T cell-APC conjugates, triggered TCRs are rapidly
      removed from the cell surface and are degraded in the lysosomal compartment.

PMID- 9151712
TI  - CXCR4/fusin is not a species-specific barrier in murine cells for HIV-1 entry.
AB  - Since some murine cells expressing human CD4 fail to internalize HIV-1, another
      block was thought to be located at the level of viral entry in addition to CD4.
      Recently, CXCR4 was shown to function as a coreceptor for T cell line-tropic HIV
      1 entry. Here we demonstrated that cells expressing murine CXCR4 and human CD4
      fused with cells expressing the env proteins derived from T cell line-tropic HIV
      1 and were infected with T cell line-tropic HIV-1 strains. In contrast, the same
      cells were not infected with chimeric clones constructed by substitution of
      monocyte- or macrophage-tropic strain-derived env region or V3 region into T cell
      line-tropic HIV-1, indicating V3 loop of envelope protein is required for murine
      CXCR4mediated HIV-1 entry. We conclude that murine CXCR4 is not a species
      specific barrier to the entry of T cell line-tropic HIV-1.

PMID- 9151713
TI  - The nasal-associated lymphoid tissue of adult mice acts as an entry site for the
      mouse mammary tumor retrovirus.
AB  - Mouse mammary tumor virus (MMTV) is a B type retrovirus transmitted to the
      suckling offspring through milk. MMTV crosses the intestinal barrier of neonates,
      initially infects the lymphoid cells of the Peyer's patches, and later spreads to
      all lymphoid organs and to the mammary gland. Adult mice can be infected
      systemically, but not by oral MMTV administration. In this study, we show that
      nasal administration of infected milk induces the infection of adult mice. Nasal
      MMTV infection shared the main features of systemic and neonatal intestinal MMTV
      infections: deletion of the superantigen (SAg)-reactive T cell subset from the
      peripheral T cell population, presence of viral DNA in lymphoid cells, and
      transmission of MMTV from mother to offspring. Viral DNA was restricted to the
      lungs and nasal-associated lymphoid tissue (NALT) 6 d after nasal infection.
      Furthermore, SAg-induced T cell proliferation was only detected in NALT. These
      results demonstrate that MMTV crosses the intact epithelium of the upper
      respiratory tract of adult mice and infects the lymphoid follicles associated
      with these structures.

PMID- 9151714
TI  - The Vav binding site (Y315) in ZAP-70 is critical for antigen receptor-mediated
      signal transduction.
AB  - Stimulation of antigen receptors in T and B cells leads to the activation of the
      Src and Syk families of protein tyrosine kinases (PTK). These PTKs subsequently
      phosphorylate numerous intracellular substrates, including the 95-kD
      protooncogene product Vav. Vav is essential for both T and B cell development and
      T and B cell antigen receptor-mediated signal transduction. After receptor
      ligation, Vav associates with phosphorylated Syk and ZAP-70 PTKs, an interaction
      that depends upon its SH2 domain. Here we demonstrate that a point mutation of
      tyrosine 315 (Y315F) in ZAP-70, a putative Vav SH2 domain binding site,
      eliminated the Vav- ZAP-70 interaction. Moreover, the Y315 mutation impaired the
      function of ZAP-70 in antigen receptor signaling. Surprisingly, this mutation
      also resulted in marked reduction in the tyrosine phosphorylation of ZAP-70, Vav,
      SLP-76, and Shc. These data demonstrate that the Vav binding site in ZAP-70 plays
      a critical role in antigen receptor-mediated signal transduction.

PMID- 9151715
TI  - The in vivo time course for elimination of adrenalectomy-induced apoptotic
      profiles from the granule cell layer of the rat hippocampus.
AB  - Although apoptotic cellular degeneration has been reported to be extremely rapid
      with the use of in vitro models, the time needed to clear apoptotic neurons in
      the in vivo brain is unknown. In this study we used a simple morphological
      approach to solve this problem. Four days after adrenalectomy (ADX), all of the
      operated rats morphologically displayed hippocampal granule cell apoptosis that
      was prevented completely by corticosterone replacement immediately after ADX.
      Therefore, we intravenously injected the rats with corticosterone 4 d after ADX
      and subsequently maintained them on corticosterone replacement in saline drinking
      water. This corticosterone replacement could protect healthy granule cells
      promptly and continuously against hormone-deficient apoptosis, because the normal
      glucocorticoid receptor immunoreactivity within the granule cell nuclei, which
      disappeared after ADX, was identified 1 hr after corticosterone replacement was
      started, and this effect persisted for several days. However, this corticosterone
      treatment could not prevent the irreversible apoptosis of the already degenerated
      granule cells at various stages of the same progressive apoptotic process. Then
      we successively traced the disappearance of apoptotic granule cells throughout
      the hippocampus at different time points by Nissl and silver staining. Given that
      the apoptotic cells at the earliest stage of the degenerating process when the
      ADX rats received corticosterone injection were the last to disappear, the period
      from corticosterone injection until the disappearance of the last degenerating
      debris of apoptotic cells was taken to represent the time course for elimination
      of apoptotic neurons in vivo. We discovered that the elimination of apoptotic
      granule cells took 72 hr.

PMID- 9151716
TI  - Interneurons of the dentate-hilus border of the rat dentate gyrus: morphological
      and electrophysiological heterogeneity.
AB  - Interneurons located near the border of the dentate granule cell layer and the
      hilus were studied in hippocampal slices using whole-cell current clamp and
      biocytin staining. Because these interneurons exhibit both morphological and
      electrophysiological diversity, we asked whether passive electrotonic parameters
      or repetitive firing behavior correlated with axonal distribution. Each
      interneuron was distinguished by a preferred axonal distribution in the molecular
      layer or granule cell layer, and four groups could be discerned, the axons of
      which arborized in (1) the granule cell layer, (2) the inner molecular layer, (3)
      the outer molecular layer, and (4) diffusely in the molecular layer. In our
      sample, interneurons with axons arborizing diffusely in the molecular layer were
      most frequent, and those with axons restricted to the granule cell layer were
      least frequent. Resting potential, input resistance, time constant, electrotonic
      length, and spike frequency adaptation (SFA) were not significantly different
      among the four groups, and the variability in SFA between cells with similar
      axonal distributions was striking. Clear differences in action potential
      morphology and afterhyperpolarizations, however, emerged when nonadapting
      interneurons were compared with those exhibiting SFA. Interneurons exhibiting SFA
      had characteristically broader spikes, progressive slowing of action potential
      repolarization during repetitive firing, and slow afterhyperpolarizations that
      distinguished them from nonadapting interneurons. We propose that the variability
      in repetitive firing behavior and morphology exhibited by each of these
      interneurons makes each interneuron unique and may provide a high level of fine
      tuning of inhibitory control critical to information processing in the dentate.

PMID- 9151717
TI  - Suppression of cathepsins B and L causes a proliferation of lysosomes and the
      formation of meganeurites in hippocampus.
AB  - Cultured hippocampal slices exhibited prominent ultrastructural features of brain
      aging after exposure to an inhibitor of cathepsins B and L. Six days of treatment
      with N-CBZ-L-phenylalanyl-L-alanine-diazomethylketone (ZPAD) resulted in a
      dramatic increase in the number of lysosomes in the perikarya of neurons and
      glial cells throughout the slices. Furthermore, lysosomes in CA1 and CA3
      pyramidal cells were not restricted to the soma but instead were located
      throughout dendritic processes. Clusters of lysosomes were commonly found within
      bulging segments of proximal dendrites that were notable for an absence of
      microtubules and neurofilaments. Although pyknotic nuclei were sometimes
      encountered, most of the cells in slices exposed to ZPAD for 6 d appeared
      relatively normal. Slices given 7 d of recovery contained several unique
      features, compared with those processed immediately after incubation with the
      inhibitor. Cell bodies of CA1 neurons were largely cleared of the excess
      lysosomes but had gained fusiform, somatic extensions that were filled with fused
      lysosomes and related complex, dense bodies. These appendages, similar in form
      and content to structures previously referred to as "meganeurites," were not
      observed in CA3 neurons or granule cells. Because meganeurites were often
      interposed between cell body and axon, they have the potential to interfere with
      processes requiring axonal transport. It is suggested that inactivation of
      cathepsins B and L results in a proliferation of lysosomes and that meganeurite
      generation provides a means of storing residual catabolic organelles. The
      accumulated material could be eliminated by pinching off the meganeurite but, at
      least in some cases, this action would result in axotomy. Reduced cathepsin L
      activity, increased numbers of lysosomes, and the formation of meganeurites are
      all reported to occur during brain aging; thus, it is possible that the infusion
      of ZPAD into cultured slices sets in motion a greatly accelerated gerontological
      sequence.

PMID- 9151718
TI  - Neurosteroid prolongs GABAA channel deactivation by altering kinetics of
      desensitized states.
AB  - Fast applications of GABA (1 mM) to nucleated and outside-out patches excised
      from granule neurons in cerebellar slices from developing rats evoked currents
      with a double exponential time course reminiscent of that of IPSCs. A
      neurosteroid 3alpha, 21dihydroxy-5alpha-pregnan-20-one (THDOC) remarkably
      increased the slow deactivation time constant and slowed down recovery from
      desensitization, as estimated by paired-pulse GABA applications. THDOC also
      reduced the amplitude of GABA currents, whereas it failed to affect the fast
      deactivation component and its relative contribution to peak amplitude. The
      effects of THDOC on slow deactivation were greater in rats younger than postnatal
      day 13 (P13) as compared with rats at P30-P35. THDOC failed to alter deactivation
      of short responses induced by a less-potent agonist taurine at saturating doses.
      These responses had deactivation kinetics described by a fast single exponential
      decay, little desensitization, and quick recovery. However, THDOC slowed
      deactivation if taurine responses were long enough to allow consistent
      desensitization, suggesting that desensitized states are required for the
      neurosteroid to modulate GABA responses. In outside-out patches, just as
      desensitized states prolonged GABA responses by producing reopening of channels
      activated by brief GABA pulses, THDOC increased the channel open probability by
      further increasing the number of late channel openings, resulting in a
      prolongation of the slow deactivation. Our data suggest that neurosteroid
      potentiates the inhibitory postsynaptic transmission via the prolongation of the
      slow deactivation and that the alteration of kinetics of entry and exit from
      desensitized states underlies the allosteric modification of GABAA receptors by
      neurosteroids.

PMID- 9151719
TI  - Secondary activation of a cation conductance is responsible for NMDA toxicity in
      acutely isolated hippocampal neurons.
AB  - One of the key questions concerning glutamate toxicity is how a transient NMDA
      exposure can lead to a delayed death of neurons. To address this issue, we
      performed whole-cell recording on acutely isolated hippocampal CA1 neurons to
      monitor the membrane response after NMDA exposure. Transient NMDA exposure (100
      microM, 10 min) induced an inward current (postexposure current; Ipe) which was
      associated with a Ca2+- and Na+-permeable cation conductance. Ipe continuously
      increased (in the absence of NMDA) until death of the neuron occurred.
      Application of NMDA in the absence of extracellular calcium failed to trigger Ipe
      and neuronal death. Postexposure suppression of Ipe protected against NMDA
      toxicity. These results indicate that a cation current, which is induced by an
      increase in intracellular calcium concentration ([Ca2+]i) and is itself partly
      carried by Ca2+, links the initial NMDA exposure to neuronal death.

PMID- 9151720
TI  - Immunogold localization of the dopamine transporter: an ultrastructural study of
      the rat ventral tegmental area.
AB  - The dopamine transporter (DAT) plays an important role in the plasmalemmal
      reuptake of dopamine and, thus, in the termination of normal dopaminergic
      neurotransmission. DAT is also a major binding site for cocaine and other
      stimulants, the psychoactive effects of which are associated primarily with the
      inhibition of dopamine reuptake within mesocorticolimbic dopaminergic neurons. We
      used electron microscopy with an anti-peptide antiserum directed against the N
      terminal domain of DAT to determine the subcellular localization of this
      transporter in the rat ventral tegmental area (VTA), the region that contains the
      cell bodies and dendrites of these dopaminergic neurons. We show that in the VTA,
      almost 95% of the DAT immunogold-labeled profiles are neuronal perikarya and
      dendrites, and the remainder are unmyelinated axons. Within perikarya and large
      proximal dendrites, almost all of the DAT immunogold particles are associated
      with intracellular membranes, including saccules of Golgi and cytoplasmic
      tubulovesicles. In contrast, within medium- to small-diameter dendrites and
      unmyelinated axons, most of the DAT gold particles are located on plasma
      membranes. In dually labeled tissue, peroxidase reaction product for the
      catecholamine-synthesizing enzyme tyrosine hydroxylase is present in DAT
      immunoreactive profiles. These findings suggest that intermediate and distal
      dendrites are both the primary sites of dopamine reuptake and the principal
      targets of cocaine and related psychostimulants within dopaminergic neurons in
      the VTA.

PMID- 9151721
TI  - Identification of endogenous sympathetic neuron pituitary adenylate cyclase
      activating polypeptide (PACAP): depolarization regulates production and secretion
      through induction of multiple propeptide transcripts.
AB  - The vasoactive intestinal peptide/pituitary adenylate cyclase-activating
      polypeptide (PACAP)/secretin/glucagon family of peptides displays numerous
      physiological roles in autonomic nervous system development and function. The
      regulated endogenous production and release of PACAP peptides in sympathetic
      neurons of the superior cervical ganglion (SCG) was investigated. The two
      posttranslationally processed forms of PACAP, PACAP27 and PACAP38, were
      identified in rat adult, neonatal, and cultured SCG neurons. PACAP38 levels were
      approximately 5-10 fmol/adult SCG and approximately 2 fmol/neonatal SCG; PACAP27
      levels were comparable. The authenticity of peptide immunoreactivity in these
      tissues was verified by coelution with synthetic PACAP in reverse-phase HPLC
      analysis. Reverse transcription-PCR and sequence-specific hybridization revealed
      PACAP mRNA in adult, neonatal, and cultured SCG neurons; in situ hybridization
      histochemistry and immunocytochemistry localized the PACAP peptide and proPACAP
      mRNA to a subset of the SCG neuronal population. Basal and stimulated release of
      endogenous PACAP38 from cultured sympathetic neurons was established, suggesting
      that these peptides may function as signaling molecules at target tissues.
      Chronic depolarization with 40 mM potassium stimulated the PACAP secretory rate
      10- to 20-fold, with concomitant increases in cellular PACAP peptide and mRNA
      levels. When examined using Northern analysis, depolarizing conditions not only
      stimulated the 2.2 kb form of PACAP mRNA, but also induced the expression of a
      shortened, 0.9 kb, transcript. Further reverse-transcription PCR analysis
      demonstrated that this smaller transcript was not identical to the unique
      testicular message. These studies identify PACAP38 and PACAP27 as regulated
      endogenous releasable peptides contributing to the functional diversity and
      phenotypic plasticity of the sympathetic nervous system.

PMID- 9151722
TI  - Dysregulation of diurnal rhythms of serotonin 5-HT2C and corticosteroid receptor
      gene expression in the hippocampus with food restriction and glucocorticoids.
AB  - Both serotonergic dysfunction and glucocorticoid hypersecretion are implicated in
      affective and eating disorders. The adverse effects of serotonergic (5-HT)2C
      receptor activation on mood and food intake, the antidepressant efficacy of 5-HT2
      receptor antagonists, and the hyperphagia observed in 5-HT2C receptor knockout
      mice all suggest a key role for increased 5-HT2C receptor-mediated
      neurotransmission. Glucocorticoids, however, downregulate 5-HT2C receptor mRNA in
      the hippocampus, and it is unclear how increased 5-HT2C receptor sensitivity is
      achieved in the presence of elevated glucocorticoid levels in depression. Here we
      show a monophasic diurnal rhythm of 5-HT2C receptor mRNA expression in the rat
      hippocampus that parallels time-dependent variations in 5-HT2C receptor agonist
      induced behaviors in open field tests. Rats entrained to chronic food restriction
      show marked but intermittent corticosterone hypersecretion and maintain an
      unaltered 5-HT2C receptor mRNA rhythm. The 5-HT2C receptor mRNA rhythm, however,
      is suppressed by even modest constant elevations of corticosterone (adrenalectomy
      + pellet) or with elevated corticosterone during the daytime (8 A.M.), whereas a
      normal rhythm exists in animals that have the same dose of corticosterone in the
      evening (6 P.M.). Thus, animals showing even a transient daytime corticosterone
      nadir exhibit normal hippocampal 5-HT2C receptor mRNA rhythms, even in the
      presence of overt corticosterone hypersecretion. Chronic food restriction also
      abolishes the normal diurnal variation in hippocampal glucocorticoid receptor
      (GR) and mineralocorticoid receptor mRNAs and produces, unusually, both elevated
      corticosterone and increased GR. The mismatch between elevated glucocorticoids
      and maintained 5-HT2C receptor and increased GR gene expression in the
      hippocampus provides a new model to dissect mechanisms that may underlie
      affective and eating disorders.

PMID- 9151723
TI  - Somatostatin inhibits excitatory transmission at rat hippocampal synapses via
      presynaptic receptors.
AB  - Somatostatin is one of the major peptides in interneurons of the hippocampus. It
      is believed to play a role in memory formation and to reduce the susceptibility
      of the hippocampus to seizure-like activity. However, at the cellular level, the
      actions of somatostatin on hippocampal neurons are still controversial, ranging
      from inhibition to excitation. In the present study, we measured autaptic
      currents of hippocampal neurons isolated in single-neuron microcultures.
      Somatostatin and the analogous peptides seglitide and octreotide reduced
      glutamatergic, but not GABAergic, autaptic currents via pertussis toxin-sensitive
      G-proteins. This effect was observed whether autaptic currents were mediated by
      NMDA or non-NMDA glutamate receptors. Furthermore, somatostatin did not affect
      currents evoked by the direct application of glutamate, but reduced the frequency
      of spontaneously occurring excitatory autaptic currents. These results show that
      presynaptic somatostatin receptors of the SRIF1 family inhibit glutamate release
      at hippocampal synapses. Somatostatin, seglitide, and octreotide also reduced the
      frequency of miniature excitatory postsynaptic currents in mass cultures without
      affecting their amplitudes. In addition, all three agonists inhibited voltage
      activated Ca2+ currents at neuronal somata, but failed to alter K+ currents,
      effects that were also abolished by pertussis toxin. Thus, presynaptic
      somatostatin receptors in the hippocampus selectively inhibit excitatory
      transmission via G-proteins of the Gi/Go family and through at least two separate
      mechanisms, the modulation of Ca2+ channels and an effect downstream of Ca2+
      entry. This presynaptic inhibition by somatostatin may provide a basis for its
      reportedly anticonvulsive action.

PMID- 9151724
TI  - A novel basal promoter element is required for expression of the rat tyrosine
      hydroxylase gene.
AB  - Transcription of the rat tyrosine hydroxylase (TH) gene is controlled by enhancer
      sequences in its 5' flanking region; these enhancers include the AP1, dyad, and
      cAMP response element (CRE) motifs. We show that a novel basal promoter element (
      17 GCCTGCCTGGCGA -5) positioned between the TATA box and +1 works in conjunction
      with the upstream AP1-dyad and CRE enhancers but cannot support transcription by
      itself. A mutation of this element, termed partial dyad, reduces basal expression
      of a reporter gene in TH-positive cell lines and TH-negative lines but has no
      effect on cAMP- or KCl-induced expression. A double mutant at positions -17 and 
      11 of the partial dyad reduces transcriptional activation by 80%. Conversely,
      insertion of this element into a heterologous promoter restores basal expression
      to levels mediated by the native TH promoter. The partial dyad is a novel
      activational element that is required for full expression of the TH gene and may
      assist in the function of the AP1, dyad, and CRE motifs and also other enhancers
      further upstream. Hence, the rat TH gene is unusual in that its enhancers will
      not function with a heterologous promoter but require a specific TH promoter
      sequence for full activation.

PMID- 9151725
TI  - Pigment-dispersing hormone shifts the phase of the circadian pacemaker of the
      cockroach Leucophaea maderae.
AB  - An antiserum against the crustacean neuropeptide pigment-dispersing hormone
      stains a small set of neurons in the optic lobes of several hemimetabolous and
      holometabolous insects. These cells, the primary branches of which in the optic
      lobe lie in the accessory medulla, fulfill several criteria predicted for neurons
      of the circadian clock. For example, in fruit flies they express timeless and
      period, which are two molecular components of the circadian pacemaker. To test
      whether pigment-dispersing hormone fulfills a circadian function in the cockroach
      Leucophaea maderae, 150 fmol of synthetic peptide was injected into the vicinity
      of the accessory medulla. This resulted in a stable phase-dependent resetting of
      the phase of the circadian locomotor activity rhythm, which depended on the
      amount of pigment-dispersing hormone injected. The resulting phase-response curve
      differs from that obtained with light pulses, suggesting that pigment-dispersing
      hormone-immunoreactive neurons are not part of the visual input pathway to the
      pacemaker but an integral part of it and/or part of a nonphotic input into the
      clock. A possible role of these neurons in coupling the bilaterally paired
      circadian pacemakers is discussed.

PMID- 9151726
TI  - The monomeric G-proteins Rac1 and/or Cdc42 are required for the inhibition of
      voltage-dependent calcium current by bradykinin.
AB  - Although regulation of voltage-dependent calcium current (ICa,V) by
      neurotransmitters is a ubiquitous mechanism among nerve cells, the signaling
      pathways involved are not well understood. We have determined previously that in
      a neuroblastoma-glioma hybrid cell line (NG108-15), the heterotrimeric G-protein
      G13 mediates the inhibition of ICa,V produced by bradykinin (BK) via an unknown
      mechanism. Various reports indicate that G13 can couple to RhoA, Rac1, and Cdc42,
      which are closely related members of the Rho family of monomeric G-proteins. We
      have investigated their role as signaling intermediates in the pathway used by BK
      to inhibit ICa,V. Using immunoblot analysis and the PCR, we found evidence that
      RhoA, Rac1, and Cdc42 all are expressed in NG108-15 cells. Intracellularly
      perfused recombinant Rho-GDI (an inhibitor of guanine nucleotide exchange
      specific for the Rho family) attenuated the inhibition of ICa,V by BK. These
      findings indicate that activation of RhoA, Rac1, or Cdc42 may be required for the
      response to BK. To determine whether any of these monomeric G-proteins mediate
      the response to BK, we have intracellularly applied blocking antibodies specific
      for each of the candidate proteins. Only the anti-Rac1 antibody blocked the
      response to BK. In parallel experiments, peptides corresponding to the C-terminal
      regions of Rac1 and Cdc42 blocked the same response. These data indicate a novel
      functional contribution of Rac1 and possibly also of Cdc42 to the inhibition of
      ICa,V by neurotransmitters.

PMID- 9151727
TI  - The responses of rat trigeminal ganglion neurons to capsaicin and two nonpungent
      vanilloid receptor agonists, olvanil and glyceryl nonamide.
AB  - Capsaicin, the pungent ingredient in hot pepper, activates and subsequently
      desensitizes a subset of polymodal nociceptors. Because its initial application
      to skin produces pain, nonpungent analogs such as olvanil and glyceryl nonivamide
      (GLNVA) were synthesized to enhance its clinical use. To explore how these
      nonpungent analogs differ from capsaicin, whole-cell patch-clamp recordings were
      performed on cultured rat trigeminal ganglion neurons. In neurons held at -60 mV,
      capsaicin, olvanil, and GLNVA were found to activate one or two kinetically
      distinct inward currents. Two inward currents were also activated when
      extracellular Ca2+ was replaced with Ba2+ and also when intracellular chloride
      was replaced by aspartate. The reversal potentials of the rapidly and slowly
      activating currents were 15.3 +/- 6 and -4.0 +/- 2.5 mV, respectively. These data
      provide strong evidence for subtypes of vanilloid receptors. One difference among
      these agonists is that, on average, the activation kinetics of the currents
      evoked by 1 microM olvanil and 30 microM GLNVA are considerably slower than those
      evoked by 1 microM capsaicin. Measurements of the peak current, Ip, versus
      agonist concentration were fit to the Hill equation to yield values of the half
      maximal concentrations (K1/2), and the Hill coefficients (n). For capsaicin,
      olvanil, and GLNVA, K1/2 = 0.68, 0.59, and 27.0 microM and n = 1.38, 1.32, and
      1.24, respectively. We propose that olvanil and GLNVA are nonpungent because they
      activate different subtypes of receptors and/or because of their activation
      kinetics (compared with capsaicin) are, on average, slower than the rate they
      inhibit action potentials from polymodal nociceptors.

PMID- 9151728
TI  - Bone morphogenetic proteins induce astroglial differentiation of oligodendroglial
      astroglial progenitor cells.
AB  - We have used bipotent postnatal cortical oligodendroglial-astroglial progenitor
      cells (O-2As) to examine the role of inductive signals in astroglial lineage
      commitment. O-2A progenitor cells undergo progressive oligodendroglial
      differentiation when cultured in serum-free medium, but differentiate into
      astrocytes in medium supplemented with FBS. We now report that the bone
      morphogenetic proteins (BMPs), a major subclass of the transforming growth factor
      beta (TGFbeta) superfamily, promote the selective, dose-dependent differentiation
      of O-2As into astrocytes with concurrent suppression of oligodendroglial
      differentiation. This astroglial-inductive action is not sanctioned by other
      members of the TGFbeta superfamily. Astroglial differentiation requires only very
      brief initial exposure to the BMPs and is accompanied by increased cellular
      survival and accelerated exit from cell cycle. Dual-label immunofluorescence
      microscopy documents that O-2A progenitor cells express a complement of BMP type
      I and type II receptor subunits required for signal transduction. Furthermore,
      expression of BMP2 in vivo reaches maximal levels during the period of
      gliogenesis. These results suggest that the BMPs act as potent inductive factors
      in postnatal glial lineage commitment that initiate a stable program of
      astroglial differentiation.

PMID- 9151729
TI  - Neuritic outgrowth associated with astroglial phenotypic changes induced by
      antisense glial fibrillary acidic protein (GFAP) mRNA in injured neuron-astrocyte
      cocultures.
AB  - In the adult CNS, axons fail to regenerate after injury. Among the cell
      interactions that lead to this failure are those developed with astrocytes. In an
      effort to elucidate the mechanisms underlying these negative interactions, we
      have used astrocytes treated with antisense glial fibrillary acidic protein
      (GFAP) mRNA to inhibit the formation of gliofilaments, indispensable for the
      astroglial morphological response to injury, and have studied their permissivity
      for neuritic outgrowth. In a neuron-astrocyte coculture, a mechanical lesion led
      to hypertrophy of astrocytes neighboring the lesion. Neuronal cell bodies and
      neurites were absent both from the area of lesion and from its surroundings.
      Reactive astrocytes appeared, therefore, to be a nonpermissive substrate.
      Transfection that used antisense GFAP mRNA blocked astroglial morphological
      changes and was characterized by both a persistence of neuronal cell bodies in
      the vicinity of the lesion site and a growth of neurites into the same region.
      These morphological differences were associated with a 46% decrease in the GFAP
      translation capacity and a 50% increase in the concentration of GAP-43 in the
      treated cultures. Neurons were associated mainly with an extracellular laminin
      network, which was predominant at the lesion site in treated cocultures. In
      contrast, those astrocytes highly laminin-immunoreactive appeared to be a
      nonpermissive substrate for neurons. These results show that inhibition in GFAP
      synthesis, leading to a reduction of astroglial hypertrophy, relieves the
      blockade of neuritic outgrowth that normally is observed after a lesion. The
      mechanisms may involve changes in the secretion of extracellular matrix molecules
      by astrocytes.

PMID- 9151730
TI  - Control of action potential-induced Ca2+ signaling in the soma of hippocampal
      neurons by Ca2+ release from intracellular stores.
AB  - Stimulus-induced increases in neuronal Ca2+ concentration are important signaling
      events for transcriptional regulation and neuronal plasticity. Electrical inputs
      are thought to mediate Ca2+ responses in the soma by triggering action
      potentials, which in turn open voltage-gated Ca2+ channels in the somatic plasma
      membrane. It is not yet known to what extent internal Ca2+ amplification
      contributes to the somatic Ca2+ responses. Here we used fluorescent Ca2+
      measurements in cultured hippocampal neurons and report that the amplitude of the
      somatic Ca2+ increase triggered by field stimulation is independent of the
      extracellular Ca2+ concentration as long as the concentration is greater than 50
      microM. Furthermore, significantly more La3+ has to be added extracellularly for
      blocking Ca2+ responses, as predicted from the reported La3+ dependence of
      voltage-gated Ca2+ channels. These measurements suggest that field stimulation
      induced somatic Ca2+ responses in hippocampal neurons are largely attributable to
      Ca2+ release from intracellular stores. Only a small number of Ca2+ ions have to
      enter across the plasma membrane for this intracellular Ca2+ amplification
      process to occur. Rapid fluorescence-imaging measurements showed that the
      internal Ca2+ amplification occurs over 10-15 msec and linearly increases
      intracellular Ca2+ concentrations for up to 40 action potentials. At a fixed
      number of field pulses, frequencies of 40 Hz were optimal for somatic Ca2+
      increases. Our studies suggest that the opening of intracellular Ca2+ release
      channels plays a crucial part in shaping the action potential-induced neuronal
      Ca2+ response.

PMID- 9151731
TI  - Calcium entry through cyclic nucleotide-gated channels in individual cilia of
      olfactory receptor cells: spatiotemporal dynamics.
AB  - Transient elevations of intracellular Ca2+ play an important role in regulating
      the sensitivity of olfactory transduction, but such elevations have not been
      demonstrated in the olfactory cilia, which are the site of primary odor
      transduction. To begin to understand Ca2+ signaling in olfactory cilia, we used
      high-resolution imaging techniques to study the Ca2+ transients that occur in
      salamander olfactory receptor neurons (ORNs) as a result of cyclic nucleotide
      gated (CNG) channel activation. To visualize ciliary Ca2+ signals, we loaded ORNs
      with the Ca2+ indicator dye Fluo-3 AM and measured fluorescence with a laser
      scanning confocal microscope. Application of the phosphodiesterase inhibitor IBMX
      increased fluorescence in the cilia and other neuronal compartments; the ciliary
      signal occurred first and was more transient. This signal could be abolished by
      lowering external Ca2+ or by applying LY83583, a potent blocker of CNG channels,
      indicating that Ca2+ entry through CNG channels was the primary source of
      fluorescence increases. Direct activation of CNG channels with low levels of 8-Br
      cGMP (1 microM) led to tonic Ca2+ signals that were restricted locally to the
      cilia and the dendritic knob. Elevated external K+, which depolarizes cell
      membranes, increased fluorescence signals in the cell body and dendrite but
      failed to increase ciliary Ca2+ fluorescence. The results demonstrate the
      existence and spatiotemporal properties of Ca2+ transients in individual
      olfactory cilia and implicate CNG channels as a major pathway for Ca2+ entry into
      ORN cilia during odor transduction.

PMID- 9151732
TI  - The characterization of the Olf-1/EBF-like HLH transcription factor family:
      implications in olfactory gene regulation and neuronal development.
AB  - The Olf-1/EBF helix-loop-helix (HLH) transcription factor has been implicated in
      olfactory gene regulation and in B-cell development. Using homology screening
      methods, we identified two additional Olf-1/EBF-like cDNAs from a mouse embryonic
      cDNA library. The Olf-1/EBF-like (O/E) proteins O/E-1, O/E-2, and O/E-3 define a
      family of transcription factors that share structural similarities and
      biochemical activities. Although these O/E genes are expressed within olfactory
      epithelium in an identical pattern, they exhibit different patterns of expression
      in the developing nervous system. Although O/E-1 mRNA is present in several
      tissues in addition to olfactory neurons and developing B-cells, O/E-2 and O/E-3
      are expressed at high levels only in olfactory tissue. In O/E-1 knock-out
      animals, the presence of two additional O/E family members in olfactory neurons
      may provide redundancy and allow normal olfactory neurodevelopment. Further, the
      identification of the O/E family of HLH transcription factors and their embryonic
      expression patterns suggest that the O/E proteins may have a more general
      function in neuronal development.

PMID- 9151733
TI  - Cloning and functional characterization of Roaz, a zinc finger protein that
      interacts with O/E-1 to regulate gene expression: implications for olfactory
      neuronal development.
AB  - We have identified a protein, Rat O/E-1-associated zinc finger protein (Roaz),
      that plays a role in regulating the temporal and spatial pattern of olfactory
      neuronal-specific gene expression. This protein functions by interacting with the
      olfactory factor O/E-1 and modulating its transcriptional activity. Roaz,
      isolated via a yeast two-hybrid screen, encoded a protein containing 29 C2H2 zinc
      fingers of the TFIIIA type. The Roaz mRNA was found in brain, eye, olfactory
      epithelium, spleen, and heart. In situ hybridization data indicated that Roaz was
      expressed in the basal layer, consisting of neural precursor cells and immature
      sensory neurons of the olfactory epithelium, but not in the mature receptor
      cells. We showed that the Roaz protein bound specifically to O/E-1 by using the
      yeast two-hybrid system. The two proteins formed a stable complex in
      coimmunoprecipitation and in vitro binding assays. Introduction of Roaz and O/E-1
      into cells containing an olfactory promoter-driven luciferase reporter
      demonstrated that Roaz abolished O/E-1-mediated transcriptional activation. We
      propose that the function of Roaz is to modulate negatively the transactivational
      activity of O/E-1 and to act as a switch protein in the coordination of olfactory
      sensory neuron differentiation.

PMID- 9151734
TI  - Slow-channel transgenic mice: a model of postsynaptic organellar degeneration at
      the neuromuscular junction.
AB  - The slow-channel congenital myasthenic syndrome (SCCMS) is a dominantly inherited
      disorder of neuromuscular transmission characterized by delayed closure of the
      skeletal muscle acetylcholine receptor (AChR) ion channel and degeneration of the
      neuromuscular junction. The identification of a series of AChR subunit mutations
      in the SCCMS supports the hypothesis that the altered kinetics of the endplate
      currents in this disease are attributable to inherited abnormalities of the AChR.
      To investigate the role of these mutant AChR subunits in the development of the
      synaptic degeneration seen in the SCCMS, we have studied the properties of the
      AChR mutation, epsilonL269F, found in a family with SCCMS, using both in vitro
      and in vivo expression systems. The mutation causes a sixfold increase in the
      open time of AChRs expressed in vitro, similar to the phenotype of other reported
      mutants. Transgenic mice expressing this mutant develop a syndrome that is highly
      reminiscent of the SCCMS. Mice have fatigability of limb muscles,
      electrophysiological evidence of slow AChR ion channels, and defective
      neuromuscular transmission. Pathologically, the motor endplates show focal
      accumulation of calcium and striking ultrastructural changes, including
      enlargement and degeneration of the subsynaptic mitochondria and nuclei. These
      findings clearly demonstrate the role of this mutation in the spectrum of
      abnormalities associated with the SCCMS and point to the subsynaptic organelles
      as principal targets in this disease. These transgenic mice provide a useful
      model for the study of excitotoxic synaptic degeneration.

PMID- 9151735
TI  - Reduction of CuZn-superoxide dismutase activity exacerbates neuronal cell injury
      and edema formation after transient focal cerebral ischemia.
AB  - Apoptotic neuronal cell death has recently been associated with the development
      of infarction after cerebral ischemia. In a variety of studies, CuZn-superoxide
      dismutase (CuZn-SOD) has been shown to protect the brain from ischemic injury. A
      possible role for CuZn-SOD-related modulation of neuronal viability is suggested
      by the finding that CuZn-SOD inhibits apoptotic neuronal cell death in response
      to some forms of cellular damage. We evaluated this possibility in the model of
      transient focal cerebral ischemia in mice bearing a disruption of the CuZn-SOD
      gene (Sod1). Homozygous mutant (Sod1 -/-) mice had no detectable CuZn-SOD
      activity, and heterozygous mutants (Sod1 +/-) showed a 50% decrease compared with
      wild-type mice. Sod1 -/- mice showed a high level of blood-brain barrier
      disruption soon after 1 hr of middle cerebral artery occlusion and 100% mortality
      at 24 hr after ischemia. Sod1 +/- mice showed 30% mortality at 24 hr after
      ischemia, and neurological deficits were exacerbated compared with wild-type
      controls. The Sod1 +/- animals also had increased infarct volume and brain
      swelling, accompanied by increased apoptotic neuronal cell death as indicated by
      the in situ nick-end labeling technique to detect DNA fragmentation and
      morphological criteria. These results suggest that oxygen-free radicals,
      especially superoxide anions, are an important factor for the development of
      infarction by brain edema formation and apoptotic neuronal cell death after focal
      cerebral ischemia and reperfusion.

PMID- 9151736
TI  - Upregulation of the endosomal-lysosomal pathway in the trembler-J neuropathy.
AB  - A nonconservative leucine to proline mutation in peripheral myelin protein 22
      (PMP22) causes the Trembler-J (TrJ) neuropathy in mice and humans. The expression
      levels and localization of the PMP22 protein in the TrJ mouse have not been
      previously determined. The aim of our studies was to reevaluate the extent of
      myelin deficit in genotyped heterozygous and homozygous animals and to examine
      how the TrJ mutation alters the normal in vivo post-translational processing of
      PMP22. Morphological studies show evidence for primary dysmyelination and myelin
      instability in affected animals. As expected, Western blot analysis indicates
      that in adult heterozygous TrJ animals, the level of PMP22 is markedly decreased,
      similar to myelin basic protein and protein zero, whereas myelin-associated
      glycoprotein is largely unaffected. The decrease in myelin protein expression is
      associated with an increase in lysosomal biogenesis, suggestive of augmented
      endocytosis or autophagy. Double-immunolabeling experiments show the accumulation
      of PMP22 in endosomal/lysosomal structures of TrJ Schwann cells, and chloroquine
      treatment of nerve segments indicates that the degradation of protein zero,
      PMP22, and myelin basic protein is augmented in TrJ nerves. These studies suggest
      that the TrJ mutation alters myelin stability and that the mutant protein is
      likely degraded via the lysosomal pathway.

PMID- 9151737
TI  - Neurotrophins protect cultured cerebellar granule neurons against the early phase
      of cell death by a two-component mechanism.
AB  - Cerebellar granule neurons cultured with serum develop a mature neuronal
      phenotype, including stimulus-coupled release of glutamate, and depend on
      elevated potassium for survival. We find that cells cultured with serum undergo
      two phases of cell death. By 6 d in vitro, 30-50% of the cells present are dead;
      after this time the remaining cells die. Elevated potassium prevents only this
      later phase of death, whereas neurotrophins protect these cells against the early
      phase of death. Factors that bind p75(NTR) or TNF-R, members of the same receptor
      family, exhibit voltage-sensitive calcium channel-dependent protection, whereas
      ligands of expressed Trk receptors show additional calcium channel-independent
      protection. The cells express TrkB protein and show elevated c-Fos and c-Jun
      levels in response to BDNF. No TrkA is detected, although p75(NTR) protein is
      expressed and NGF induces depolarization-dependent elevation of c-Jun levels. In
      the presence of the protein kinase C inhibitor bisindolylmaleimide, BDNF-induced
      survival promotion is reduced partially, whereas NGF-induced death is unmasked.
      Basal survival mechanisms are insensitive to inhibition of PK-C or PI-3 kinase.
      We conclude that BDNF promotes survival in part via its TrkB receptor, whereas
      there is an additional pathway promoting survival and elevating c-Jun evoked by
      both NGF and BDNF via a non-Trk receptor.

PMID- 9151738
TI  - Alzheimer's presenilin mutation sensitizes neural cells to apoptosis induced by
      trophic factor withdrawal and amyloid beta-peptide: involvement of calcium and
      oxyradicals.
AB  - Most autosomal dominant inherited forms of early onset Alzheimer's disease (AD)
      are caused by mutations in the presenilin-1 (PS-1) gene on chromosome 14. PS-1 is
      an integral membrane protein with six to nine membrane-spanning domains and is
      expressed in neurons throughout the brain wherein it is localized mainly in
      endoplasmic reticulum (ER). The mechanism or mechanisms whereby PS-1 mutations
      promote neuron degeneration in AD are unknown. Recent findings suggest links
      among deposition of amyloid beta-peptide (Abeta), oxidative stress, disruption of
      ion homeostasis, and an apoptotic form of neuron death in AD. We now report that
      expression of the human PS-1 L286V mutation in PC12 cells increases their
      susceptibility to apoptosis induced by trophic factor withdrawal and Abeta.
      Increases in oxidative stress and intracellular calcium levels induced by the
      apoptotic stimuli were exacerbated greatly in cells expressing the PS-1 mutation,
      as compared with control cell lines and lines overexpressing wild-type PS-1. The
      antiapoptotic gene product Bcl-2 prevented apoptosis after NGF withdrawal from
      differentiated PC12 cells expressing mutant PS-1. Elevations of [Ca2+]i in
      response to thapsigargin, an inhibitor of the ER Ca2+-ATPase, were increased in
      cells expressing mutant PS-1, and this adverse effect was abolished in cells
      expressing Bcl-2. Antioxidants and blockers of calcium influx and release from ER
      protected cells against the adverse consequences of the PS-1 mutation. By
      perturbing cellular calcium regulation and promoting oxidative stress, PS-1
      mutations may sensitize neurons to apoptotic death in AD.

PMID- 9151739
TI  - Tissue inhibitor of metalloproteinases-1 (TIMP-1) is differentially induced in
      neurons and astrocytes after seizures: evidence for developmental, immediate
      early gene, and lesion response.
AB  - We investigated in vivo the expression of the tissue inhibitor of
      metalloproteinases-1 (TIMP-1) in the rat CNS after kainate (KA)-induced
      excitotoxic seizures. In situ hybridization revealed that TIMP-1 mRNA is induced
      rapidly and massively in most regions of the adult forebrain after KA treatment.
      Neuronal activity seems to be necessary but not sufficient to trigger TIMP-1
      induction, because it is not observed in seizing 10-d-old pups, unlike what is
      observed in 21- and 35-d-old animals after seizures. The rapid induction of TIMP
      1 is not prevented by the inhibitor of protein synthesis cycloheximide,
      suggesting that, after seizures, TIMP-1 is induced in neurons as an immediate
      early gene (IEG). The initial neuronal upregulation is followed by enhanced
      expression in astrocytes, as assessed by double-labeling experiments. In the
      hippocampus rapid increases in mRNA are followed by relatively delayed (8 hr
      after KA) increases in TIMP-1 immunoreactivity in the perisomatic and dendro
      axonic areas, suggesting secretion of the protein. At 3 d after KA treatment,
      strong immunoreactivity is found in astrocytes and in the cell bodies and dendro
      axonic projections of resistant neurons such as the dentate granule cells. Taken
      together, the results suggest that TIMP-1 may be instrumental for neurons and
      astrocytes in coupling early cellular events triggered by seizures with the
      regulation of long-lasting changes involved in tissue reorganization and/or
      neuroprotection.

PMID- 9151740
TI  - A new form of inherited red-blindness identified in zebrafish.
AB  - A red-blind zebrafish mutant, partial optokinetic response b (pob), has been
      isolated by measuring eye movements of larvae in a three-generation screen for
      recessive mutations affecting the visual system. pob larvae exhibit eye movements
      in response to rotating black and white stripes illuminated with white light, but
      they do not move their eyes when the stripes are illuminated with red light.
      Physiological, immunohistochemical, and in situ hybridization analyses of pob
      retinas showed a selective loss of red-sensitive cones at 5 days
      postfertilization (dpf). At 3 dpf, cells expressing red opsin are present,
      suggesting that red-sensitive cones form initially but then disappear rapidly,
      whereas other photoreceptors remain. Linkage analysis indicated that the mutation
      identified in the pob mutant is not at the red opsin locus. Because red opsin is
      the only known molecule unique to red cones, these data suggest that a novel gene
      is required for the maintenance or function of red cones.

PMID- 9151741
TI  - Implication of OTX2 in pigment epithelium determination and neural retina
      differentiation.
AB  - The expression pattern of Otx2, a homeobox-containing gene, was analyzed from the
      beginning of eye morphogenesis until neural retina differentiation in chick
      embryos. Early on, Otx2 expression was diffuse throughout the optic vesicles but
      became restricted to their dorsal part when the vesicles contacted the surface
      ectoderm. As the optic cup forms, Otx2 was expressed only in the outer layer,
      which gives rise to the pigment epithelium. This early Otx2 expression pattern
      was complementary to that of PAX2, which localizes to the ventral half of the
      developing eye and optic stalk. Otx2 expression was always observed in the
      pigment epithelium at all stages analyzed but was extended to scattered cells
      located in the central portion of the neural retina around stage 22. The number
      of cells expressing Otx2 transcripts increased with time, following a central to
      peripheral gradient. Bromodeoxyuridine labeling in combination with
      immunohistochemistry with anti-OTX2 antiserum and different cell-specific markers
      were used to determine that OTX2-positive cells are postmitotic neuroblasts
      undergoing differentiation into several, if not all, of the distinct cell types
      present in the chick retina. These data indicate that Otx2 might have a double
      role in eye development. First, it might be necessary for the early specification
      and subsequent functioning of the pigment epithelium. Later, OTX2 expression
      might be involved in retina neurogenesis, defining a differentiation feature
      common to the distinct retinal cell classes.

PMID- 9151742
TI  - Presynaptic initiation by action potentials of retrograde signals in developing
      neurons.
AB  - Until recently, the only means by which electrical activity was believed to
      initiate retrograde signals was via postsynaptic events: modulated synthesis or
      release of trophic factors. We have evidence in chick embryos for a presynaptic
      initiation of retrograde signals from the retina to the isthmo-optic nucleus,
      which is known to undergo 55% neuron death between embryonic days 12 and 17 and
      to become laminated during this period. Intraocular injections of saxitoxin just
      before embryonic day 14 reduce neuron death and prevent lamination in the isthmo
      optic nucleus within as few as 6 hr. We show that these rapid effects are
      attributable to the direct action of saxitoxin on the isthmo-optic terminals.
      Alternative possibilities, such as an indirect effect via the target cells, are
      ruled out by control experiments. Normally, action potentials may lead to a chain
      of second messenger events in the axon terminal that is signaled retrogradely via
      the transport of a long-lived second messenger.

PMID- 9151743
TI  - Neurotrophin-3 promotes the differentiation of muscle spindle afferents in the
      absence of peripheral targets.
AB  - The neurons of the dorsal root ganglia (DRG) that supply muscle spindles require
      target-derived factors for survival. One necessary factor for these neurons is
      neurotrophin-3 (NT3). To determine whether NT3 can promote the survival of these
      neurons in the absence of other target-derived factors, we analyzed the effects
      of exogenous NT3 after early limb bud deletion in the chick. In control embryos,
      limb bud deletion eliminated approximately 90% of the trkC-positive (trkC+)
      neurons in lumbar DRG on the deleted side. In addition, the deletion led to a
      dramatic loss of collateral sensory projections to motoneurons. Exogenous NT3
      restored a normal population of trkC+ neurons in lumbar DRG on the deleted side
      and increased the number of trkC+ neurons in DRG with normal targets
      (contralateral lumbar and thoracic). The effect was highly selective; NT3
      increased the number of trkC+ neurons without significantly changing the number
      of either trkA+ or trkB+ neurons. The effect of NT3 was attributable to the
      rescue of DRG neurons from cell death, because exogenous NT3 reduced the number
      of pyknotic nuclei without significantly altering proliferation. Analysis of
      spinal projections showed further that many of the trkC+ neurons rescued by NT3
      projected to the ventral spinal cord. These neurons thus had central projections
      characteristic of muscle spindle afferents. Together, our results indicate that
      NT3 signaling is both necessary and sufficient for the development of the
      proprioceptive phenotype, even in the absence of other signals from limb muscle.

PMID- 9151745
TI  - Selective expression of dopamine D3 receptor mRNA in proliferative zones during
      embryonic development of the rat brain.
AB  - We studied by in situ hybridization histochemistry the expression of D3 receptor
      (D3R) mRNA at various stages of rat brain development. The first expression of
      D3R mRNA was detected at embryonic day 14 (E14) in the striatal and
      rhinencephalic neuroepithelia and throughout the tectal neuroepithelium. From E16
      to E19 D3R mRNA expression extended along a rostrocaudal axis to additional
      proliferative ventricular zones of the basal forebrain, including the
      neuroepithelia of the olfactory bulb, nucleus accumbens, septum, and amygdala,
      whereas D1 and D2 receptor (D1R and D2R) mRNAs were expressed predominantly by
      migrating neuroblasts and/or differentiating striatal neurons. Only a few
      neuroblasts, migrating in the lateral cortical stream or developing as cerebellar
      Purkinje cells, expressed D3R mRNA from E18. At birth D3R expression mRNA
      appeared in differentiating neuronal fields of the nucleus accumbens and medial
      mamillary body primordia and on P5 reached a distribution similar to that found
      in adult. In addition, a transient upregulation was detected on P5 in the medial
      mamillary bodies, parietofrontal cortex, and olfactory tubercle. In the adult
      brain D3R gene expression continued in the striatal proliferative subventricular
      zone. The late expression D3R mRNA in neurons, after achievement of dopamine
      innervation, supports the existence of a regulating factor released from dopamine
      neurons, as suggested by denervation studies in the adult. The sustained and
      abundant D3R gene expression, predominantly in germinative neuroepithelial zones
      actively involved in neurogenesis of most basal forebrain structures, supports
      the hypothesis of a neurogenetic but minor morphogenetic modulatory role for the
      D3R during CNS development.

PMID- 9151744
TI  - Norepinephrine facilitates the development of the murine sweat response but is
      not essential.
AB  - During development, the sympathetic neurons innervating sweat glands undergo a
      neurotransmitter switch from noradrenergic to cholinergic between postnatal day
      (P) 4, when the sympathetic neurons first contact the sweat glands, and P21.
      Several in vitro experiments suggest that norepinephrine (NE), produced by
      sympathetic neurons, stimulates sweat glands to produce a factor that then
      induces the phenotypic switch. We tested this hypothesis in vivo using dopamine
      beta-hydroxylase-deficient mice (DBH -/-), which are unable to synthesize NE and
      epinephrine, and tyrosine hydroxylase-deficient mice (TH -/-), which are unable
      to synthesize any catecholamines. The cholinergic agonist pilocarpine and
      electrostimulation of the sciatic nerve both elicited a sweat response in adult
      DBH -/- mice that was indistinguishable from the response of controls, and the
      cholinergic antagonist atropine effectively blocked these responses. We did note,
      however, a 1- to 2-week delay in the acquisition of the sweat response in DBH -/-
      mice. Although diminished in magnitude, a sweat response to pilocarpine was also
      noted in TH -/- mice at P21. Immunohistochemistry demonstrated that TH and
      vasoactive intestinal peptide were detectable at P14 and increased to adult
      levels by P21 in DBH +/- and DBH -/- mice. These observations indicate that NE is
      not essential for the acquisition of the cholinergic phenotype, but it may
      facilitate its postnatal development.

PMID- 9151746
TI  - Competition among the axonal projections of an identified neuron contributes to
      the retraction of some of those projections.
AB  - AP neurons in the embryonic leech CNS extend lateral projections to peripheral
      targets through the ganglionic nerve roots and longitudinal projections toward
      neighboring ganglia through the connective nerves. The lateral projections grow
      extensively in the periphery; in contrast, the longitudinal projections achieve
      relatively little growth and eventually retract, the majority having essentially
      disappeared by the end of embryogenesis. Cutting both nerve roots, which
      eliminates both lateral projections, however, induces the longitudinal
      projections of the AP neuron to begin to grow rapidly toward adjacent ganglia
      within 14 hr after the axotomy. By using a laser microbeam to cut just the
      lateral projections of the AP cells, we further show that it is indeed the loss
      of its lateral projections, and not a secondary response to the cutting of other
      components of the root nerves, that induces the longitudinal projections of the
      AP cell to grow extensively. In addition, we report that reducing the outgrowth
      of the lateral projections by: (1) cutting only one lateral projection, or (2)
      ablating pioneer neurons required by the AP neuron to establish its peripheral
      arbor, also results in a significant increase in the growth of the longitudinal
      projections. Finally, we demonstrate that increasing the outgrowth of the
      longitudinal projections by ablating the AP cells in adjacent ganglia results in
      a significant reduction in the outgrowth of the lateral projections. Taken
      together, these results indicate, first, that the longitudinal and lateral
      projections usually grow at the expense of each other, and second, that normally
      the extensive outgrowth of its lateral projections is a necessary condition for a
      developing AP neuron to retract its longitudinal projections.

PMID- 9151747
TI  - The fusiform face area: a module in human extrastriate cortex specialized for
      face perception.
AB  - Using functional magnetic resonance imaging (fMRI), we found an area in the
      fusiform gyrus in 12 of the 15 subjects tested that was significantly more active
      when the subjects viewed faces than when they viewed assorted common objects.
      This face activation was used to define a specific region of interest
      individually for each subject, within which several new tests of face specificity
      were run. In each of five subjects tested, the predefined candidate "face area"
      also responded significantly more strongly to passive viewing of (1) intact than
      scrambled two-tone faces, (2) full front-view face photos than front-view photos
      of houses, and (in a different set of five subjects) (3) three-quarter-view face
      photos (with hair concealed) than photos of human hands; it also responded more
      strongly during (4) a consecutive matching task performed on three-quarter-view
      faces versus hands. Our technique of running multiple tests applied to the same
      region defined functionally within individual subjects provides a solution to two
      common problems in functional imaging: (1) the requirement to correct for
      multiple statistical comparisons and (2) the inevitable ambiguity in the
      interpretation of any study in which only two or three conditions are compared.
      Our data allow us to reject alternative accounts of the function of the fusiform
      face area (area "FF") that appeal to visual attention, subordinate-level
      classification, or general processing of any animate or human forms,
      demonstrating that this region is selectively involved in the perception of
      faces.

PMID- 9151748
TI  - How is a sensory map read Out? Effects of microstimulation in visual area MT on
      saccades and smooth pursuit eye movements.
AB  - To generate behavioral responses based on sensory input, motor areas of the brain
      must interpret, or "read out," signals from sensory maps. Our experiments tested
      several algorithms for how the motor systems for smooth pursuit and saccadic eye
      movements might extract a usable signal of target velocity from the distributed
      representation of velocity in the middle temporal visual area (MT or V5). Using
      microstimulation, we attempted to manipulate the velocity information within MT
      while monkeys tracked a moving visual stimulus. We examined the effects of the
      microstimulation on smooth pursuit and on the compensation for target velocity
      shown by saccadic eye movements. Microstimulation could alter both the speed and
      direction of the motion estimates of both types of eye movements and could also
      cause monkeys to generate pursuit even when the visual target was actually
      stationary. The pattern of alterations suggests that microstimulation can
      introduce an additional velocity signal into MT and that the pursuit and saccadic
      systems usually compute a vector average of the visually evoked and
      microstimulation-induced velocity signals (pursuit, 55 of 122 experiments;
      saccades, 70 of 122). Microstimulation effects in a few experiments were
      consistent with vector summation of these two signals (pursuit, 6 of 122;
      saccades, 2 of 122). In the remainder of the experiments, microstimulation caused
      either an apparent impairment in motion processing (pursuit, 47 of 122; saccades,
      41 of 122) or had no effect (pursuit, 14 of 122; saccades, 9 of 122). Within
      individual experiments, the effects on pursuit and saccades were usually similar,
      but the occasional striking exception suggests that the two eye movement systems
      may perform motion computations somewhat independently.

PMID- 9151749
TI  - Vasopressin/serotonin interactions in the anterior hypothalamus control
      aggressive behavior in golden hamsters.
AB  - Studies in several species of rodents show that arginine vasopressin (AVP) acting
      through a V1A receptor facilitates offensive aggression, i.e., the initiation of
      attacks and bites, whereas serotonin (5-HT) acting through a 5-HT1B receptor
      inhibits aggressive responding. One area of the CNS that seems critical for the
      organization of aggressive behavior is the basolateral hypothalamus, particularly
      the anterior hypothalamic region. The present studies examine the neuroanatomical
      and neurochemical interaction between AVP and 5-HT at the level of the anterior
      hypothalamus (AH) in the control of offensive aggression in Syrian golden
      hamsters. First, specific V1A and 5-HT1B binding sites in the AH are shown by in
      vitro receptor autoradiography. The binding for each neurotransmitter colocalizes
      with a dense field of immunoreactive AVP and 5-HT fibers and putative terminals.
      Putative 5-HT synapses on AVP neurons in the area of the AH are identified by
      double-staining immunocytochemistry and laser scanning confocal microscopy. These
      morphological data predispose a functional interaction between AVP and 5-HT at
      the level of the AH. When tested for offensive aggression in a resident/intruder
      paradigm, resident hamsters treated with fluoxetine, a selective 5-HT reuptake
      inhibitor, have significantly longer latencies to bite and bite fewer times than
      vehicle-treated controls. Conversely, AVP microinjections into the AH
      significantly shorten the latency to bite and increase biting attacks. The action
      of microinjected AVP to increase offensive aggression is blocked by the
      pretreatment of hamsters with fluoxetine. These data suggest that 5-HT inhibits
      fighting, in part, by antagonizing the aggression-promoting action of the AVP
      system.

PMID- 9151750
TI  - Glial cell line-derived neurotrophic factor protects against ischemia-induced
      injury in the cerebral cortex.
AB  - Glial cell line-derived neurotrophic factor (GDNF), a recently described and
      cloned member of the transforming growth factor (TGF)-beta superfamily, has been
      shown to have marked trophic activity on several populations of central neurons.
      Survival-promoting and injury protectant activity in vitro and in vivo, using
      several paradigms, has been demonstrated for ventral mesencephalic dopaminergic
      neurons and spinal cord motoneurons. In view of a proposed commonality of
      mechanisms, involving intracellular free radical generation, depolarization
      induced Ca2+ influx, and mitochondrial respiratory enzyme injury, between such
      GDNF-responsive paradigms and those of ischemia-induced injury, we tested the
      effects of GDNF on the extent of neural degeneration induced by transient middle
      cerebral artery (MCA) occlusion. We now report that intracerebroventricular and
      intraparenchymal administration of GDNF potently protects the cerebral
      hemispheres from damage induced by MCA occlusion. In addition, the increase in
      nitric oxide that accompanies MCA occlusion and subsequent reperfusion is blocked
      almost completely by GDNF. Thus, this protein may play an important role in the
      treatment of cerebrovascular occlusive disease.

PMID- 9151751
TI  - Firing properties of head direction cells in the rat anterior thalamic nucleus:
      dependence on vestibular input.
AB  - Vestibular information influences spatial orientation and navigation in
      laboratory animals and humans. Neurons within the rat anterior thalamus encode
      the directional heading of the animal in absolute space. These neurons, referred
      to as head direction (HD) cells, fire selectively when the rat points its head in
      a specific direction in the horizontal plane with respect to the external
      laboratory reference frame. HD cells are thought to represent an essential
      component of a neural network that processes allocentric spatial information. The
      functional properties of HD cells may be dependent on vestibular input. Here,
      anterior thalamic HD cells were recorded before and after sodium arsanilate
      induced vestibular system lesion. Vestibular lesions abolished the directional
      firing properties of HD cells. The time course of disruption in the directional
      firing properties paralleled the loss of vestibular function. Arsanilate-treated
      rats exhibited only minor changes in locomotor behavior, which were unlikely to
      account for the loss of direction-specific firing. Vestibular lesions also
      disrupted the influence of angular head velocity on anterior thalamic single-unit
      firing rates. Finally, a subset of anterior thalamic neurons recorded from
      vestibular-lesioned rats exhibited a pattern of intermittent firing bursts that
      were distinctly unrelated to HD. This novel anterior thalamic firing pattern has
      not been encountered in any vestibular-intact rat. These data suggest that: (1)
      the neural code for directional bearing is critically dependent on vestibular
      information; and (2) this loss of HD cell information may represent a
      neurobiological mechanism to account for the orientation and navigational
      deficits observed after vestibular dysfunction.

PMID- 9151752
TI  - Local blockade of sodium channels by tetrodotoxin ameliorates tissue loss and
      long-term functional deficits resulting from experimental spinal cord injury.
AB  - Although relatively little is known of the mechanisms involved in secondary
      axonal loss after spinal cord injury (SCI), recent data from in vitro models of
      white matter (WM) injury have implicated abnormal sodium influx as a key event.
      We hypothesized that blockade of sodium channels after SCI would reduce WM loss
      and long-term functional deficits. To test this hypothesis, a sufficient and safe
      dose (0.15 nmol) of the potent Na+ channel blocker tetrodotoxin (TTX) was
      determined through a dose-response study. We microinjected TTX or vehicle (VEH)
      into the injury site at 15 min after a standardized contusive SCI in the rat.
      Behavioral tests were performed 1 d after injury and weekly thereafter.
      Quantitative histopathology at 8 weeks postinjury showed that TTX treatment
      significantly reduced tissue loss at the injury site, with greater effect on
      sparing of WM than gray matter. TTX did not change the pattern of chronic
      histopathology typical of this SCI model, but restricted its extent, tripled the
      area of residual WM at the epicenter, and reduced the average length of the
      lesions. Serotonin immunoreactivity caudal to the epicenter, a marker for
      descending motor control axons, was nearly threefold that of VEH controls. The
      increase in WM at the epicenter was significantly correlated with the decrease in
      functional deficits. The TTX group exhibited a significantly enhanced recovery of
      coordinated hindlimb functions, more normal hindlimb reflexes, and earlier
      establishment of a reflex bladder. The results demonstrate that Na+ channels play
      a critical role in WM loss in vivo after SCI.

PMID- 9151753
TI  - Transient changes in flocculonodular lobe protein kinase C expression during
      vestibular compensation.
AB  - Protein kinase C (PKC) is a family of intracellular signal transduction enzymes,
      comprising isoforms that vary in sensitivity to calcium, arachidonic acid, and
      diacylglycerol. PKC isoforms alpha, gamma, and delta are expressed by cerebellar
      Purkinje cells and neurons in the cerebellar nuclei and vestibular nuclei of the
      Long-Evans rat. In control rats, these PKCs are distributed symmetrically in the
      flocculonodular-lobe Purkinje cells. Behavioral recovery from vestibular
      dysfunction produced by unilateral labyrinthectomy (UL) is accompanied by
      asymmetric expression of PKC isoforms in these regions within 6 hr after UL.
      These expression changes were localized within parasagittal regions of the
      flocculus and nodulus. The distribution of PKCalpha, -gamma, and -delta were
      identical, suggesting that they are coregulated in cerebellar Purkinje cells
      during this early compensatory period. The pattern of Purkinje cell PKC
      expression returned to the control, symmetric distribution within 24 hr after UL.
      It is hypothesized that these regional changes in Purkinje cell PKC expression
      are an early intracellular signal contributing to vestibular compensation. In
      particular, regulation of PKC expression may contribute to changes in the
      efficacy of cerebellar synaptic plasticity during the acute post-UL period.

PMID- 9151754
TI  - Paradoxical effects of external modulation of inhibitory interneurons.
AB  - The neocortex, hippocampus, and several other brain regions contain populations
      of excitatory principal cells with recurrent connections and strong interactions
      with local inhibitory interneurons. To improve our understanding of the
      interactions among these cell types, we modeled the dynamic behavior of this type
      of network, including external inputs. A surprising finding was that increasing
      the direct external inhibitory input to the inhibitory interneurons, without
      directly affecting any other part of the network, can, in some circumstances,
      cause the interneurons to increase their firing rates. The main prerequisite for
      this paradoxical response to external input is that the recurrent connections
      among the excitatory cells are strong enough to make the excitatory network
      unstable when feedback inhibition is removed. Because this requirement is met in
      the neocortex and several regions of the hippocampus, these observations have
      important implications for understanding the responses of interneurons to a
      variety of pharmacological and electrical manipulations. The analysis can be
      extended to a scenario with periodically varying external input, where it
      predicts a systematic relationship between the phase shift and depth of
      modulation for each interneuron. This prediction was tested by recording from
      interneurons in the CA1 region of the rat hippocampus in vivo, and the results
      broadly confirmed the model. These findings have further implications for the
      function of inhibitory and neuromodulatory circuits, which can be tested
      experimentally.

PMID- 9151755
TI  - Neuropeptide hierarchies and the activation of sequential motor behaviors in the
      hawkmoth, Manduca sexta.
AB  - In insects, the shedding of the old cuticle at the end of a molt involves a
      stereotyped sequence of distinct behaviors. Our studies on the isolated nervous
      system of Manduca sexta show that the peptides ecdysis-triggering hormone (ETH)
      and crustacean cardioactive peptide (CCAP) elicit the first two motor behaviors,
      the pre-ecdysis and ecdysis behaviors, respectively. Exposing isolated abdominal
      ganglia to ETH resulted in the generation of sustained pre-ecdysis bursts. By
      contrast, exposing the entire isolated CNS to ETH resulted in the sequential
      appearance of pre-ecdysis and ecdysis motor outputs. Previous research has shown
      that ETH activates neurons within the brain that then release eclosion hormone
      within the CNS. The latter elevates cGMP levels within and increases the
      excitability of a group of neurons containing CCAP. In our experiments, the ETH
      induced onset of ecdysis bursts was always associated with a rise in
      intracellular cGMP within these CCAP neurons. We also found that CCAP
      immunoreactivity decreases centrally during normal ecdysis. Isolated, desheathed
      abdominal ganglia responded to CCAP by generating rhythmical ecdysis bursts.
      These ecdysis motor bursts persisted as long as CCAP was present and could be
      reinduced by successive application of the peptide. CCAP exposure also actively
      terminated pre-ecdysis bursts from the abdominal CNS, even in the continued
      presence of ETH. Thus, the sequential performance of the two behaviors arises
      from one modulator activating the first behavior and also initiating the release
      of the second modulator. The second modulator then turns off the first behavior
      while activating the second.

PMID- 9151756
TI  - The low-affinity neurotrophin receptor p75 regulates the function but not the
      selective survival of specific subpopulations of sensory neurons.
AB  - Mice with a targeted deletion of the low-affinity neurotrophin receptor p75 (p75
      /-) exhibit a 50% loss of large- and small-diameter sensory neurons in the dorsal
      root ganglion. Using neurophysiological recording techniques, we now show that
      p75 is not required for the survival of specific, functionally defined
      subpopulations of sensory neurons. Rather, p75-/- mice exhibit losses of neurons
      that subserve nociceptive as well as non-nociceptive functions. The receptive
      properties of large myelinated afferent fibers were normal in p75-/- mice.
      However, the receptive properties of subpopulations of afferent fibers with thin
      myelinated or unmyelinated axons were strikingly impaired in mice lacking p75.
      Furthermore, the presence of p75 is required for normal mechanotransduction in C
      fibers and D-hair receptors and normal heat sensitivity in A-fiber nociceptors.

PMID- 9151757
TI  - Temperature dependency of basal and evoked release of amino acids and calcitonin
      gene-related peptide from rat dorsal spinal cord.
AB  - Moderate hypothermia significantly diminishes consequences of spinal and cerebral
      anoxia. One component of this neuroprotection has been hypothesized to be
      suppression of excitotoxic transmitter release. Whether this suppression is
      attributable to reduced hypoxic injury that induces release or an alteration of
      the release process itself is unclear. We sought to characterize the temperature
      sensitivity (Q10) of basal and evoked calcitonin gene-related peptide (CGRP) and
      amino acid release from dorsal horn slices of rat spinal cord over a range of
      temperatures from 40 to 8 degrees C. At 40 degrees C, potassium (60 mM) and
      capsaicin (10 microM) evoked a 21- and 32-fold increase in basal CGRP
      concentrations, respectively. Capsaicin had no effect on glutamate release, but
      potassium evoked a 2.7-fold increase. Release evoked by either potassium or
      capsaicin was reduced in a biphasic fashion with declining temperature. Over the
      range of 40 to 34 degrees C, the Q10 values for evoked release for CGRP were 11.3
      (potassium) and 39.7 (capsaicin) and for glutamate, 5. 5 (potassium). Over the
      range of 34 to 8 degrees C, Q10 values were near unity for all evoked release
      (0.8 and 1.3 for CGRP and 1.2 for glutamate). Although serine, glycine,
      glutamine, taurine, and citrulline showed no evoked release, basal levels were
      reduced at temperatures below 34 degrees C. The pronounced temperature dependency
      of evoked transmitter release between 40 and 34 degrees C is consistent with the
      profound cerebral protection observed with mild hypothermia in which metabolic
      activity is only slightly depressed.

PMID- 9151758
TI  - Metabotropic glutamate agonist-induced rotation: a pharmacological, FOS
      immunohistochemical, and [14C]-2-deoxyglucose autoradiographic study.
AB  - Metabotropic glutamate receptors (mGluRs) are a major class of excitatory amino
      acid receptors. Eight mGluR subtypes, coupled to a variety of effector systems,
      have been cloned. These receptors have been classified into three groups based on
      amino acid sequence homology, effector systems, and pharmacological profile.
      Group I mGluRs increase phosphoinositide turnover, whereas groups II and III
      mGluRs are negatively coupled to adenylyl cyclase. The striatum possesses a high
      density of mGluR binding sites, and several mGluR mRNAs and proteins are
      expressed by striatal neurons. In rats, unilateral striatal injection of the
      nonsubtype selective mGluR agonist 1-aminocyclopentane-1S,3R-dicarboxylic acid
      (1S,3R-ACPD) results in contralateral rotation with delayed onset, thought to be
      secondary to an increase in dopamine release. We sought to determine the mGluR
      subtype(s) involved, the modulation of the rotation by other basal ganglia
      neurotransmitter systems, and the functional anatomy underlying the rotational
      behavior. The group I mGluR agonist 3,5-dihydroxyphenylglycine (DHPG) induced
      contralateral rotation in a dose-dependent manner, whereas group II and group III
      agonists were ineffective. Rotation induced by DHPG or 1S,3R-ACPD was attenuated
      by group I antagonists, but not by group II or group III antagonists. This
      suggests that the rotation is mediated by group I mGluRs. Rotation induced by
      DHPG or 1S,3R-ACPD was attenuated by pretreatment with antagonists at muscarinic
      cholinergic, adenosine A2, dopamine D2, or dopamine D1 receptors. Examination of
      FOS-like immunoreactivity after group I and group II mGluR agonist administration
      suggests increased activity in the striatopallidal pathway. However, [14C]-2
      deoxyglucose uptake studies indicate increased activity in nuclei of the
      striatopallidal (indirect) pathway, particularly in the subthalamic nucleus, only
      after group I mGluR activation.

PMID- 9151759
TI  - Synaptic enhancement and enhanced excitability in presynaptic and postsynaptic
      neurons in the conditioned stimulus pathway of Hermissenda.
AB  - Identified type A photoreceptors of Hermissenda express differential effects of
      classical conditioning. Lateral type A photoreceptors exhibit an increase in
      excitability to both the conditioned stimulus (CS; light) and extrinsic current.
      In contrast, medial type A photoreceptors do not express enhanced excitability,
      but do show enhancement of the medial B to medial A synaptic connection.
      Therefore, both enhanced excitability and changes in synaptic strength may
      contribute to long-term plasticity underlying classical conditioning. The
      activation of protein kinase C (PKC) is involved in the induction of enhanced
      excitability of identified type B photoreceptors produced by one-trial
      conditioning and the expression of enhanced excitability in B photoreceptors
      after multitrial classical conditioning. We have examined a possible role for
      persistent kinase activity in the expression of enhanced excitability in lateral
      type A photoreceptors and enhancement of the medial B to medial type A synaptic
      connection after classical conditioning. Injection of the PKC inhibitor peptide
      PKC(19-36) into medial type B photoreceptors of conditioned animals did not
      significantly change the amplitude of medial A IPSPs elicited by single spikes in
      the medial B photoreceptor. Injections of PKC(19-36) into medial B photoreceptors
      of pseudorandom controls also did not significantly change the amplitude of IPSPs
      recorded from the medial A photoreceptor. In contrast, spikes elicited by
      extrinsic current in lateral type A photoreceptors of conditioned animals were
      significantly reduced in frequency after intracellular injection of PKC(19-36) as
      compared with pseudorandom controls. Injection of the noninhibitory analog
      peptide [glu27]PKC(19-36) did not affect excitability. Thus, enhanced
      excitability in the lateral A photoreceptor of conditioned animals seems to be
      influenced, in part, by a constitutively active kinase or a persistent kinase
      activator, whereas synaptic enhancement of the connection between the medial B
      and medial A photoreceptors of conditioned animals may involve a different
      mechanism.

PMID- 9151760
TI  - GABA in the nucleus accumbens shell participates in the central regulation of
      feeding behavior.
AB  - We have demonstrated previously that injections of 6, 7-dinitroquinoxaline-2,3
      dione into the nucleus accumbens shell (AcbSh) elicits pronounced feeding in
      satiated rats. This glutamate antagonist blocks AMPA and kainate receptors and
      most likely increases food intake by disrupting a tonic excitatory input to the
      AcbSh, thus decreasing the firing rate of a population of local neurons. Because
      the application of GABA agonists also decreases neuronal activity, we
      hypothesized that administration of GABA agonists into the AcbSh would stimulate
      feeding in satiated rats. We found that acute inhibition of cells in the AcbSh
      via administration of the GABAA receptor agonist muscimol or the GABAB receptor
      agonist baclofen elicited intense, dose-related feeding without altering water
      intake. Muscimol-induced feeding was blocked by coadministration of the selective
      GABAA receptor blocker bicuculline, but not by the GABAB receptor blocker
      saclofen. Conversely, baclofen-induced feeding was blocked by coadministration of
      saclofen, but was not affected by bicuculline. Furthermore, we found that
      increasing local levels of GABA by administration of a selective GABA
      transaminase inhibitor, gamma-vinyl-GABA, elicited robust feeding in satiated
      rats, suggesting a physiological role for endogenous AcbSh GABA in the control of
      feeding. A mapping study showed that although some feeding can be elicited by
      muscimol injections near the lateral ventricles, the ventromedial AcbSh is the
      most sensitive site for eliciting feeding. These findings demonstrate that
      manipulation of GABA-sensitive cells in the AcbSh can have a pronounced, but
      specific, effect on feeding behavior in rats. They also constitute the initial
      description of a novel and potentially important component of the central
      mechanisms controlling food intake.

PMID- 9151761
TI  - An escalating dose/multiple high-dose binge pattern of amphetamine administration
      results in differential changes in the extracellular dopamine response profiles
      in caudate-putamen and nucleus accumbens.
AB  - Amphetamine (AMPH)-induced psychosis is most frequently associated with a chronic
      high-dose "binge" or "run" pattern of stimulant abuse, generally preceded by a
      period of gradually escalating doses of the drug. We showed previously that
      animals subjected to such a regimen of AMPH administration developed, over
      multiple daily binges, a unique pattern of behavioral response that included a
      decrease in stereotypy and a pronounced increase in locomotion. Because of the
      involvement of mesolimbic and mesostriatal dopamine (DA) pathways in locomotion
      and stereotypy, respectively, we hypothesized that a persistent shift in the
      relative magnitude of caudate-putamen (CP) and nucleus accumbens (NAC) DA
      transmission may contribute to this altered behavioral profile. To test this
      hypothesis, we examined CP and NAC extracellular DA in response to multiple high
      dose AMPH binges. Our results revealed that with multiple binges the CP DA
      response but not the NAC response developed a profound tolerance/tachyphylaxis to
      the drug-induced increase in extracellular transmitter. These differential
      regional response alterations seem to correspond to the shift in the relative
      expression of stereotypy and locomotion. We hypothesize that changes in DA
      synthesis, perhaps mediated by regionally specific adaptations in DA autoreceptor
      function, contribute to the differential extracellular transmitter response
      profiles, and suggest that these neurochemical changes may have important
      implications for the mechanisms underlying the addictive and psychotogenic
      properties of AMPH.

PMID- 9151762
TI  - Long-term intracerebroventricular infusion of corticotropin-releasing hormone
      alters neuroendocrine, neurochemical, autonomic, behavioral, and cytokine
      responses to a systemic inflammatory challenge.
AB  - Corticotropin-releasing hormone (CRH) was infused intracerebroventricularly into
      rats for 7 d via a miniosmotic pump (1 microg . microl-1 . hr-1). Body
      temperature and locomotor activity were recorded during the treatment using
      biotelemetry, whereas hippocampal serotonergic neurotransmission and free
      corticosterone levels were monitored using in vivo microdialysis on day 7 of CRH
      treatment. During the microdialysis experiment, behavioral activity was scored by
      assessing the time during which rats were active (locomotion, grooming, eating,
      drinking). Continuous intracerebroventricular infusion of CRH produced a
      transient increase in body temperature and locomotion. Moreover,
      intracerebroventricularly CRH-treated rats showed elevated free corticosterone
      levels with no apparent diurnal rhythm. Intraperitoneal administration of
      bacterial endotoxin -lipopolysaccharide (LPS); 100 microg/kg body weight- on day
      7 of CRH/vehicle treatment produced a marked fever response in control animals,
      which was significantly blunted in intracerebroventricularly CRH-treated rats.
      Although free corticosterone levels reached similar peak concentrations in both
      intracerebroventricularly vehicle- and CRH-infused groups after LPS, this
      response was delayed significantly by approximately 1 hr in the
      intracerebroventricularly CRH-treated animals. Microdialysis experiments showed
      no changes in basal extracellular levels of serotonin and 5-hydroxyindoleacetic
      acid in intracerebroventricularly CRH-infused animals. Injection of LPS in
      intracerebroventricularly CRH-treated rats produced a blunted 5-HT response and a
      delayed onset of behavioral inhibition and other signs of sickness behavior.
      Assessment of the endotoxin-induced cytokine responses showed significantly
      enhanced plasma interleukin-1 (IL-1) and IL-6 bioactivities in the
      intracerebroventricularly CRH-infused animals 3 hr after injection of LPS,
      whereas tumor necrosis factor bioactivity responses were not different. Our data
      demonstrate that chronically elevated brain CRH levels produce marked changes in
      basal (largely CRH regulated) physiological and behavioral processes accompanied
      by aberrant responses to an acute challenge. The present study provides evidence
      that chronic CRH hypersecretion is an important factor in the etiology of stress
      related disorders.

PMID- 9151763
TI  - A slow outward current activated by FMRFamide in heart interneurons of the
      medicinal leech.
AB  - The endogenous neuropeptide FMRFamide (Phe-Met-Arg-Phe-NH2) can accelerate the
      oscillation of reciprocally inhibitory pairs of interneurons that pace heartbeat
      in the medicinal leech. A model based on all available biophysical data of a two
      cell heart interneuron oscillator provides a theoretical basis for understanding
      this modulation. Previously observed modulation of K+ currents by FMRFamide
      cannot account for this acceleratory effect in the model. This observation
      prompted the present reexamination of K+ currents in heart interneurons. We
      devised better methods for separation of the various components of K+ current and
      more accurately measured their activation and deactivation kinetics. Moreover, we
      demonstrated that FMRFamide activates a previously undetected K+ current (IKF),
      which has very slow activation and deactivation kinetics. Addition of
      physiologically measured amounts of IKF to the model two-cell oscillator can
      account for the acceleratory effect of FMRFamide.

PMID- 9151764
TI  - Postnatal development of serotonergic innervation, 5-HT1A receptor expression,
      and 5-HT responses in rat motoneurons.
AB  - We compared the electrophysiological responses to serotonin (5-HT) of neonatal
      and juvenile rat hypoglossal motoneurons (HMs) by using intracellular recording
      techniques in a brainstem slice preparation. In neonatal HMs (</=P8), 5-HT caused
      a substantial decrease in the amplitude of spike afterhyperpolarization (AHP)
      that was associated with an increase in the minimal repetitive firing frequency
      (Fmin). Previous work has shown that this effect of 5-HT was mediated by the 5
      HT1A receptor and may be secondary to inhibition of N- and P/Q-type calcium
      channels. In contrast to results from neonates, we found that 5-HT did not
      inhibit the AHP in juvenile HMs (>/= P20). Application of a cocktail of calcium
      channel toxins (omega-Conotoxin-GVIA and omega-Agatoxin-IVA) to juvenile HMs
      substantially inhibited the AHP, indicating that calcium entry through N- and P/Q
      type channels supports the AHP in juvenile HMs, as it does in neonates. In
      addition, intracellular injection of the long-lasting GTP analog GTPgammaS
      induced an agonist-independent increase in Fmin similar to that seen in neonates
      in the presence of 5-HT. Together, these results suggested that intracellular
      mechanisms downstream of the 5-HT1A receptor capable of inhibiting the AHP were
      intact in juvenile HMs. Therefore, we investigated the possibility that age
      related changes in effects of 5-HT on the AHP resulted from altered expression of
      the 5-HT1A receptor. To this end, we performed ligand-binding autoradiography
      using [3H]8-OH-DPAT, a 5-HT1A agonist, and in situ hybridization using
      radiolabeled oligonucleotide probes specific for the 5-HT1A receptor. The two
      approaches gave remarkably similar results. The highest levels of 5-HT1A receptor
      expression were found in neonatal HMs, with maximal binding and hybridization at
      approximately postnatal day 7 (P7) and only low levels of receptor expression by
      P28. Finally, immunohistochemistry for 5-HT revealed that these developmental
      changes in 5-HT1A receptor expression occurred coincident with a postnatal
      increase in serotonergic innervation of the hypoglossal nucleus (nXII). Together,
      these findings indicate that developmental changes occur in the serotonergic
      innervation of nXII and in the expression of 5-HT1A receptors in HMs during the
      early postnatal period, resulting in markedly different effects of 5-HT on firing
      behavior in neonatal and juvenile HMs.

PMID- 9151765
TI  - Visual and somatosensory information about object shape control manipulative
      fingertip forces.
AB  - We investigated the importance of visual versus somatosensory information for the
      adaptation of the fingertip forces to object shape when humans used the tips of
      the right index finger and thumb to lift a test object. The angle of the two flat
      grip surfaces in relation to the vertical plane was changed between trials from 
      40 to 30 degrees. At 0 degrees the two surfaces were parallel, and at positive
      and negative angles the object tapered upward and downward, respectively.
      Subjects automatically adapted the balance between the horizontal grip force and
      the vertical lift force to the object shape and thereby maintained a rather
      constant safety margin against frictional slips, despite the huge variation in
      finger force requirements. Subjects used visual cues to adapt force to object
      shape parametrically in anticipation of the force requirements imposed once the
      object was contacted. In the absence of somatosensory information from the
      digits, sighted subjects still adapted the force coordination to object shape,
      but without vision and somatosensory inputs the performance was severely
      impaired. With normal digital sensibility, subjects adapted the force
      coordination to object shape even without vision. Shape cues obtained by
      somatosensory mechanisms were expressed in the motor output about 0. 1 sec after
      contact. Before this point in time, memory of force coordination used in the
      previous trial controlled the force output. We conclude that both visual and
      somatosensory inputs can be used in conjunction with sensorimotor memories to
      adapt the force output to object shape automatically for grasp stability.

PMID- 9151766
TI  - Effects of 4-aminopyridine on muscle and motor unit force in canine motor neuron
      disease.
AB  - Hereditary Canine Spinal Muscular Atrophy (HCSMA) is an autosomal dominant
      disorder of motor neurons that shares features with human motor neuron disease.
      In animals exhibiting the accelerated phenotype (homozygotes), we demonstrated
      previously that many motor units exhibit functional deficits that likely reflect
      underlying deficits in neurotrans-mission. The drug 4-aminopyridine (4AP) blocks
      voltage-dependent potassium conductances and is capable of increasing
      neurotransmission by overcoming axonal conduction block or by increasing
      transmitter release. In this study, we determined whether and to what extent 4AP
      could enhance muscle force production in HCSMA. Systemic 4AP (1-2 mg/kg)
      increased nerve-evoked whole muscle twitch force and electromyograms (EMG) to a
      greater extent in older homozygous animals than in similarly aged, symptomless
      HCSMA animals or in one younger homozygous animal. The possibility that this
      difference was caused by the presence of failing motor units in the muscles from
      homozygotes was tested directly by administering 4AP while recording force
      produced by failing motor units. The results showed that the twitch force and EMG
      of failing motor units could be significantly increased by 4AP, whereas no effect
      was observed in a nonfailing motor unit from a symptomless, aged-matched HCSMA
      animal. The ability of 4AP to increase force in failing units may be related to
      the extent of failure. Although 4AP increased peak forces during unit tetanic
      activation, tetanic force failure was not eliminated. These results demonstrate
      that the force outputs of failing motor units in HCSMA homozygotes can be
      increased by 4AP. Possible sites of 4AP action are considered.

PMID- 9151767
TI  - Early neuropathologic effects of mild or moderate hypoxemia after controlled
      cortical impact injury in rats.
AB  - Hypoxemia has detrimental effects after traumatic brain injury (TBI) in both
      experimental models and humans. The purpose of this study was to determine the
      effect of mild or moderate hypoxemia on early histologic and motor functional
      outcome after controlled cortical impact (CCI) in rats. Anesthetized rats
      underwent CCI and were randomized to receive mild (FiO2 = 13%, n = 6), moderate
      (FiO2 = 11%, n = 9), or no (FiO2 = 33%, n = 6) hypoxemia for 30 min after trauma.
      Sham-operated rats without hypoxemia (n = 7) were used as controls. Motor
      function (beam balance latency) was assessed on days 0-5. Rats were killed 7 days
      after injury and their brains removed for assessment of survival of hippocampal
      neurons and contusion volume. Terminal deoxynucleotidyl transferase-mediated
      biotin-dUTP nick end labeling (TUNEL) was performed on brain sections from rats
      killed at 6, 24, and 72 h after CCI and moderate hypoxemia to assess DNA
      fragmentation in situ. Mild and moderate hypoxemia augmented motor function
      deficits after CCI in a dose-dependent manner. Moderate hypoxemia after CCI
      reduced 7-day survival of CA3 neurons but not CA1 neurons vs. sham (55 [46-86]
      vs. 99 [95-130], p < 0.05, and 79 [63-86] vs. 101 [81-123], NS, respectively; %
      uninjured hemisphere, median [range]). The addition of mild or moderate hypoxemia
      did not increase contusion volume. TUNEL-positive neurons were seen in
      ipsilateral cortex and dentate gyrus at 6, 24, and 72 h after trauma, and in
      ipsilateral CA3 hippocampal neurons and thalamus at 24 and 72 h. Moderate
      hypoxemia augments CA3 neuronal death and early motor functional deficits after
      CCI. The pattern of DNA fragmentation in selectively vulnerable neurons suggests
      that apoptosis may play a role in the delayed neuronal death seen after TBI.

PMID- 9151768
TI  - Delayed administration of basic fibroblast growth factor (bFGF) attenuates
      cognitive dysfunction following parasagittal fluid percussion brain injury in the
      rat.
AB  - The present study evaluates the therapeutic effects of delayed administration of
      bFGF on cognitive dysfunction and histopathological damage following lateral
      fluid-percussion (FP) brain injury. Male Sprague-Dawley rats were trained to
      learn a visuospatial task in a Morris Water Maze (MWM) paradigm and then were
      anesthetized and subjected to either FP brain injury of moderate severity (2.5
      2.8 atm, n = 32) or surgery without brain injury (n = 10). Twenty-four hours
      postinjury, an infusion cannula connected to a mini-osmotic pump was implanted
      into the area of maximal cortical injury to continuously infuse either bFGF (2.0
      g) or vehicle for 7 days. Treatment with bFGF significantly attenuated
      posttraumatic memory dysfunction in the MWM at 8 days postinjury when compared to
      vehicle treatment (p < 0.05). The cortical lesion and significant cell loss in
      the ipsilateral CA3 region of the hippocampus, produced by FP injury, was not
      affected by bFGF treatment. However, immunohistochemical evaluation of glial
      fibrillary acidic protein revealed a trend toward increased astrocytosis in the
      injured cortex of bFGF-treated animals compared to vehicle-treated animals (p <
      0.1). These results indicate that bFGF may be efficacious in attenuating
      cognitive dysfunction associated with traumatic brain injury.

PMID- 9151769
TI  - Expression of basic fibroblast growth factor mRNA after transient focal ischemia:
      comparison with expression of c-fos, c-jun, and hsp 70 mRNA.
AB  - We have reported that basic fibroblast growth factor (bFGF) prevents retrograde
      degeneration of thalamic neurons after middle cerebral artery (MCA) occlusion. To
      identify the protective mechanism of bFGF, we examined bFGF mRNA expression in a
      model of transient focal ischemia with in situ hybridization. Compared to c-fos,
      c-jun, and hsp 70 mRNA expression, upregulation of the bFGF mRNA expression was
      delayed until 6 h after reperfusion. By 12 h, bFGF mRNA was markedly induced in
      the peri-infarcted cortex, cingulate cortex, and peri-infarcted white matter. At
      24 h and 2 days the induction of bFGF mRNA in these regions persisted, and
      disappeared by 5 day. The quantitative assessment of bFGF mRNA expression
      revealed that optical density ratios of the cingulate gyrus and the caudoputamen
      were significantly higher at 12 h, 24 h, and 2 d after reperfusion than those in
      sham controls. Microscopic observation indicated bFGF mRNA signals were present
      in several types of cortical cells, including neurons and nonneuronal cells.
      Since intrinsic bFGF, released from the damaged tissue, can influence the healing
      response through receptors upregulated by injury, it is reasonable that this
      pattern of bFGF mRNA expression parallels the bFGFR mRNA expression previously
      reported.

PMID- 9151770
TI  - Effects of the novel NMDA antagonists CP-98,113, CP-101,581 and CP-101,606 on
      cognitive function and regional cerebral edema following experimental brain
      injury in the rat.
AB  - The present study evaluated the effects of two novel N-methyl-D-aspartate (NMDA)
      receptor blockers and ifenprodil derivatives, CP-101,606 and CP-101,581, and
      their racemic mixture CP-98,113, on spatial memory and regional cerebral edema
      following experimental fluid-percussion (FP) brain injury in the rat (n = 66).
      Fifteen minutes after brain injury (2.5 atm), animals received either (1) CP
      98,113 (5 mg/kg, i.p., n = 11), (2) CP-101,581 (5 mg/kg, i.p., n = 13), (3) CP
      101,606 (6.5 mg/kg, i.p., n = 12), or (4) DMSO vehicle (equal volume, n = 12);
      followed by a continuous 24-h subcutaneous infusion of drug at a rate of 1.5
      mg/kg/h by means of miniature osmotic (Alzet) pumps implanted subcutaneously.
      Control (uninjured) animals were subjected to identical anesthesia and surgery
      without injury and received DMSO vehicle (n = 8); CP-98,113 (5 mg/kg, i.p., n =
      3); CP-101,581 (5 mg/kg, i.p., n = 3); or CP-101,606 (6.5 mg/kg, i.p., n = 3). FP
      brain injury produced a significant cognitive impairment assessed at 2 days
      postinjury using a well-characterized testing paradigm of visuospatial memory in
      the Morris Water Maze (MWM) (p < 0.001). Administration of either CP-98,113, CP
      101,581, or CP-101,606 had no effect on sham (uninjured) animals, but significant
      attenuated spatial memory impairment assessed at 2 days postinjury (p = 0.004, p
      = 0.02, or p = 0.02, respectively). Administration of CP-89,113 but not CP
      101,581 or CP-101,606 significantly reduced the extent of regional cerebral edema
      in the cortex adjacent to the site of injury (p < 0.05) and in the ipsilateral
      hippocampus (p < 0.05) and thalamus (p < 0.05). These results suggest that
      excitatory neurotransmission may play a pivotal role in the pathogenesis of
      memory dysfunction following traumatic brain injury (TBI) and that blockade of
      the NMDA receptor may significantly attenuate cognitive deficits associated with
      TBI.

PMID- 9151771
TI  - L-arginine and superoxide dismutase prevent or reverse cerebral hypoperfusion
      after fluid-percussion traumatic brain injury.
AB  - To determine whether treatment with L-arginine or superoxide dismutase (SOD)
      would prove effective in reducing cerebral hypoperfusion after traumatic brain
      injury (TBI), we measured cerebral blood flow (CBF) using laser Doppler flowmetry
      (LDF) in rats treated before or after moderate (2.2 atm) fluid-percussion (FP)
      TBI. Rats were anesthetized with isoflurane and prepared for midline FP TBI and
      then for LDF by thinning the calvaria using an air-cooled drill. Rats were then
      randomly assigned to receive sham injury, sham injury plus L-arginine (100 mg/kg,
      5 min after sham TBI), TBI plus 0.9% NaCl, TBI plus L-arginine (100 mg/kg, 5 min
      post-TBI), TBI plus SOD (24,000 U/kg pre-TBI + 1600 units/kg/min for 15 min after
      TBI), or TBI plus SOD and L-arginine. A second group of rats received TBI plus
      saline, L-, or D-arginine (100 mg/kg, 5 min after-TBI). After treatment and TBI
      or sham injury, CBF was measured continuously using LDF for 2 h and CBF was
      expressed as a percent of the preinjury baseline for 2 h after TBI. Rats treated
      with saline or D-arginine exhibited significant reductions in CBF that persisted
      throughout the monitoring period. Rats treated with L-arginine alone or in
      combination with SOD exhibited no decreases in CBF after TBI. CBF in the SOD
      treated group decreased significantly within 15 min after TBI but returned to
      baseline levels by 45 min after TBI. These studies indicate that L-arginine but
      not D-arginine administered after TBI prevents posttraumatic hypoperfusion and
      that pretreatment with SOD will restore CBF after a brief period of
      hypoperfusion.

PMID- 9151772
TI  - Neuropathology of human spinal cord injury sustained in sports-related
      activities.
AB  - The neuropathology of 20 cases of traumatic human spinal injury is described.
      Cases were classified as having "complete" or "incomplete" spinal cord injuries
      based upon the neuropathological findings. Special attention was directed to
      those cases with neuropathological evidence of continuity of long tract axons
      across the lesion but that were obtained from individuals with clinically
      complete sensory and motor loss. Clinical and neuropathological data were
      obtained from the Western Australian Spinal Cord Injury Database and were
      selected from those cases involving sports-related injuries. From the total of 20
      cases of spinal injury, 6 exhibited neuropathologically and clinically complete
      cord injuries, 4 were neuropathologically incomplete yet clinically complete, and
      4 were neuropathologically and clinically incomplete (one being motor complete
      yet sensory incomplete). The clinical/neuropathological correlation was
      indeterminate in 6 cases because of death at or shortly after the accident. The
      neuropathological findings varied with the severity of trauma and the length of
      survival. In those cases examined less than 3 months postinjury, there was
      typically swelling of the cord from vasogenic edema with petechial hemorrhage and
      myelomalacia. Central hemorrhagic necrosis was common as was hyperemia with free
      red cells present among disrupted tissue. Activated astrocytes and polymorphs or
      macrophages were observed and early stages of glial cell scar formation were
      evident. Wallerian degeneration was evident in motor tracts caudal to the level
      of insult and in sensory tracts rostral to the lesion. Cases examined 3-6 months
      postinjury often revealed multilocular cysts with gliotic walls often extending
      several millimeters above and below the primary locus of injury. In the "chronic"
      cases (i.e., those surviving more than 6 months), there was evidence of varying
      degrees of preserved long tract parenchyma, nerve root regeneration, and Schwann
      cell remyelination of long tract axons. The degree of sparing of long motor and
      sensory tract parenchyma generally correlated well with the clinical observations
      of residual function. In four cases, however, there was a residuum of motor or
      sensory tract axons that appeared to have been spared injury, but the clinical
      data reported chronically complete sensory and motor loss. The presence of
      clinically complete yet neuropathologically incomplete injury was more often
      associated with crush or flexion injuries than with extension or compression
      trauma. The preserved parenchyma in these types of lesion may provide the
      anatomical substrate for restorative intervention.

PMID- 9151773
TI  - Normal placentation: a tale that requires an epithelial-to-endothelial
      conversion.

PMID- 9151774
TI  - An antagonist of osteoclast integrins prevents experimental osteoporosis.

PMID- 9151775
TI  - Increased pressure on G protein-coupled receptor kinases.

PMID- 9151776
TI  - Heparan sulfate proteoglycans of the cardiovascular system. Specific structures
      emerge but how is synthesis regulated?

PMID- 9151777
TI  - CD1 presentation of microbial nonpeptide antigens to T cells.

PMID- 9151778
TI  - 3-Chlorotyrosine, a specific marker of myeloperoxidase-catalyzed oxidation, is
      markedly elevated in low density lipoprotein isolated from human atherosclerotic
      intima.
AB  - Oxidation of LDL may be of pivotal importance in atherogenesis, but the
      mechanisms that promote oxidation in vivo remain poorly understood. We have
      explored the possibility that one pathway involves myeloperoxidase, a heme
      protein secreted by phagocytes. Myeloperoxidase is the only human enzyme known to
      generate hypochlorous acid (HOCl), a potent oxidizing agent, at physiological
      halide concentrations. LDL exposed to the complete myeloperoxidase-H2O2-Cl-
      system underwent chlorination of its protein tyrosyl residues. Treatment of LDL
      with reagent HOCl resulted in 3-chlorotyrosine formation, implicating HOCl as an
      intermediate in the enzymatic reaction pathway. In contrast, 3-chlorotyrosine was
      undetectable in LDL oxidized by hydroxyl radical, copper, iron, hemin, glucose,
      peroxynitrite, horseradish peroxidase, lactoperoxidase, or lipoxygenase. These
      results indicate that 3-chlorotyrosine is a specific marker for LDL oxidation by
      myeloperoxidase. To address the role of myeloperoxidase in promoting LDL
      oxidation in vivo, we used stable isotope dilution gas chromatography-mass
      spectrometry to quantify 3-chlorotyrosine in human aortic tissue and in LDL
      isolated from atherosclerotic lesions. The level of 3-chlorotyrosine in
      atherosclerotic tissue obtained during vascular surgery was sixfold higher than
      that of normal aortic intima. Moreover, the level of 3-chlorotyrosine was 30-fold
      higher in LDL isolated from atherosclerotic intima compared with circulating LDL.
      The detection of 3-chlorotyrosine in human atherosclerotic lesions indicates that
      halogenation reactions catalyzed by the myeloperoxidase system of phagocytes
      constitute one pathway for protein oxidation in vivo. These findings raise the
      possibility that the myeloperoxidase-H2O2-Cl- system plays a critical role in
      converting LDL into an atherogenic form.

PMID- 9151779
TI  - Sensitivity of Kaposi's sarcoma-associated herpesvirus replication to antiviral
      drugs. Implications for potential therapy.
AB  - Using a cell line (termed BCBL-1) derived from a peripheral effusion (body cavity
      based) lymphoma latently infected with Kaposi's sarcoma-associated herpesvirus
      (KSHV), we recently reported the successful induction of KSHV replication in
      culture (Renne, R., W. Zhong, B. Herndier, M. McGrath, N. Abbey, D. Kedes, and D.
      Ganem. 1996. Nat. Med. 2:342-346). Here we report the first use of this system
      for establishing the susceptibility of KSHV to available antiviral drugs.
      Latently infected BCBL-1 cells were induced to lytic replication with phorbol
      esters; such cells secrete large numbers of KSHV virions into the culture medium.
      We assayed the ability of the antivirals to block KSHV production, as measured by
      the release of encapsidated viral DNA. The results show that KSHV replication is
      insensitive to acyclovir (9-[(2-hydroxyethoxy)-methyl]guanine) (50% inhibitory
      concentration [IC50] = 60-80 microM), but sensitive to ganciclovir (9-[1,3
      dihydroxy-2-propoxymethyl]guanine) (IC50 = 2.7-4 microM), foscarnet (trisodium
      phosphonoformate hexahydrate) (IC50 = 80-100 microM), and cidofovir (1-[(S)-3
      hydroxy-2-(phosphonomethoxy)propyl]cytosine) (IC50 = 0.5-1 microM).

PMID- 9151781
TI  - Rapamycin (sirolimus) inhibits proliferating cell nuclear antigen expression and
      blocks cell cycle in the G1 phase in human keratinocyte stem cells.
AB  - Because the immunosuppressant rapamycin (sirolimus) blocks T cell proliferation
      in G1 phase, it has been proposed as a potential treatment for psoriasis, a skin
      disease characterized by T cell activation and keratinocyte stem cell
      hyperproliferation. To determine another potentially important mechanism through
      which rapamycin can act as an antipsoriatic agent, we tested its direct effect on
      keratinocyte stem cell proliferation in vitro as well as in vivo. In vivo cell
      cycle quiescent (G0 phase) stem cell keratinocytes in primary culture
      sequentially express de novo cyclin D1 and proliferating cell nuclear antigen
      (PCNA), prior to S phase entry, and upregulate beta1 integrin. Rapamycin
      inhibited the growth of keratinocytes that were leaving quiescence as well as
      those already in cell cycle without affecting cell viability. Although beta1
      integrin(bright) expression was not affected, the number of beta1
      integrin(bright) cells entering S/G2/M was significantly lowered by rapamycin.
      Cells treated with rapamycin exhibited decreased PCNA expression while cyclin D1
      expression, which precedes PCNA expression in the cell cycle, was not affected.
      We found similar effects on stem cell keratinocytes in patients with psoriasis
      treated systemically with rapamycin. Because PCNA is required for cell cycle
      progression from G1 to S phase, our data indicate that inhibition of PCNA protein
      synthesis may be an important regulatory element in the ability of rapamycin to
      exert a G1 block.

PMID- 9151780
TI  - G-protein-coupled receptor kinase activity is increased in hypertension.
AB  - Impaired vascular beta-adrenergic responsiveness may play an important role in
      the development and/or maintenance of hypertension. This defect has been
      associated with an alteration in receptor/guanine nucleotide regulatory protein
      (G-protein) interactions. However, the locus of this defect remains unclear. G
      Protein-coupled receptor kinases (GRKs) phosphorylate serine/threonine residues
      on G-protein-linked receptors in an agonist-dependent manner. GRK activation
      mediates reduced receptor responsiveness and impaired receptor/G-protein
      coupling. To determine whether the impairment in beta-adrenergic response in
      human hypertension might be associated with altered GRK activity, we studied
      lymphocytes from younger hypertensive subjects as compared with older and younger
      normotensive subjects. We assessed GRK activity by rhodopsin phosphorylation and
      GRK expression by immunoblot. GRK activity was significantly increased in
      lymphocytes from younger hypertensive subjects and paralleled an increase in GRK
      2 (beta ARK-1) protein expression. In contrast, no alterations in cAMP-dependent
      kinase (A-kinase) activity or GRK-5/6 expression were noted. GRK activity was not
      increased in lymphocytes from older normotensive subjects who demonstrated a
      similar impairment in beta-adrenergic-mediated adenylyl cyclase activation. These
      studies indicate that GRK activity is selectively increased in lymphocytes from
      hypertensive subjects. The increase in GRK activity may underlie the reduction in
      beta-adrenergic responsiveness characteristic of the hypertensive state.

PMID- 9151782
TI  - Cloning and sequencing of the pancreatic islet neogenesis associated protein
      (INGAP) gene and its expression in islet neogenesis in hamsters.
AB  - Induction of islet neogenesis by cellophane wrapping (CW) reverses streptozotocin
      induced (STZ) diabetes. Administration of Ilotropin, a protein extract isolated
      from CW pancreata, causes recapitulation of normal islet ontogeny and reverses
      STZ diabetes, reducing mortality by 50%. We investigated the hypothesis that a
      novel gene encoding a constituent of Ilotropin was expressed in the hamster
      pancreas undergoing islet neogenesis. Islet neogenesis associated protein (INGAP)
      is a product of a novel gene expressed in regenerating hamster pancreas. Northern
      blot analysis showed a strong single transcript of 850 bp at 1 and 2 d after CW
      that disappeared by the 6th day and was absent from untreated control pancreata.
      INGAP gene is expressed in acinar cells, but not in islets. Western blot analysis
      demonstrated the presence of INGAP in Ilotropin but not in extracts from control
      pancreata. A synthetic pentadecapeptide, corresponding to a region unique to
      INGAP, stimulated a 2.4-fold increase in [3H]thymidine incorporation into hamster
      duct epithelium in primary culture and a rat pancreatic duct cell line but had no
      effect on a hamster insulinoma tumor cell line. A portion of human INGAP gene was
      cloned and appears to be highly homologous to the hamster gene. This data
      suggests that the INGAP gene is a novel pancreatic gene expressed during islet
      neogenesis whose protein product is a constituent of Ilotropin and is capable of
      initiating duct cell proliferation, a prerequisite for islet neogenesis.

PMID- 9151783
TI  - The role of alveolar macrophages in Pneumocystis carinii degradation and
      clearance from the lung.
AB  - Although studies indicate that alveolar macrophages participate in host defense
      against Pneumocystis carinii, their role in organism degradation and clearance
      from the lung has not yet been established. We, therefore, quantified the uptake
      and degradation of 35S-labeled P. carinii by cultured macrophages, demonstrating
      significant degradation of P. carinii over 6 h. We further evaluated the role of
      macrophages in elimination of P. carinii from the living host. Rats received
      either intratracheal PBS, liposomal PBS (L-PBS), or liposomal dichloromethylene
      diphosphonate (L-Cl2MDP), a preparation which leads to selective depletion of
      macrophages. Over 72 h, L-Cl2MDP-treated animals had loss of > 85% of their
      alveolar macrophages. In contrast, L-PBS-treated rats had cellular differentials
      identical to rats receiving PBS. Macrophage-depleted rats and controls were next
      inoculated with P. carinii and organism clearance was determined after 24 h. P.
      carinii elimination was evaluated with both cyst counts and an ELISA directed
      against glycoprotein A (gpA), the major antigen of P. carinii. Both assays
      indicated that macrophage-depleted rats had substantial inpairment of P. carinii
      clearance compared to L-PBS- or PBS-treated rats. These data provide the first
      direct evidence that macrophages mediate elimination of P. carinii from the
      living host.

PMID- 9151784
TI  - Transcellular activation of platelets and endothelial cells by bioactive lipids
      in platelet microparticles.
AB  - Microparticles are released during platelet activation in vitro and have been
      detected in vivo in syndromes of platelet activation. They have been reported to
      express both pro- and anticoagulant activities. Nevertheless, their functional
      significance has remained unresolved. To address the mechanism(s) of cellular
      activation by platelet microparticles, we examined their effects on platelets and
      endothelial cells. Activation of human platelets by diverse stimuli (thrombin,
      0.1 U/ml; collagen, 4 microg/ml; and the calcium ionophore A23187, 1 microM)
      results in shedding of microparticles. Pretreatment of these particles, but not
      membrane fractions from resting platelets, with (s)PLA2 evokes a dose-dependent
      increase in platelet aggregation, intracellular [Ca2+] movement, and inositol
      phosphate formation. These effects localize to the arachidonic acid fraction of
      the microparticles and are mimicked by arachidonic acid isolated from them.
      However, platelet activation requires prior metabolism of microparticle
      arachidonic acid to thromboxane A2. Thus, pretreatment of platelets with the
      cyclooxygenase (COX) inhibitor, indomethacin (20 microM), the thromboxane
      antagonist SQ29,548 (1 microM), or the protein kinase C inhibitor GF109203X (5
      microM) prevents platelet activation by microparticles. However, platelet
      microparticles fail to evoke an inositol phosphate response directly, via either
      of the cloned thromboxane receptor isoforms stably expressed in human embryonic
      kidney (HEK) 293 cells. Prelabeling platelets with [2H(8)] arachidonate was used
      to demonstrate platelet metabolism of the microparticle-derived substrate to
      thromboxane. Platelet microparticles can also induce expression of COX-2 and
      prostacyclin (PGI2) production, but not expression of COX-1, in human endothelial
      cells. These effects are prevented by pretreatment with actinomycin D (12 microM)
      or cycloheximide (5 microg/ml). Expression of COX-2 is again induced by the
      microparticle arachidonate fraction, which it may then use to synthesize PGI2.
      Both PGE2 and iloprost, a stable PGI2 analog, evoke human umbilical vein
      endothelial cell COX-2 expression, albeit with kinetics that differ from the
      response to platelet microparticles. These studies indicate a novel mechanism of
      transcellular lipid metabolism whereby platelet activation may be amplified or
      modulated by concentrated delivery of arachidonic acid to adjacent platelets and
      endothelial cells.

PMID- 9151785
TI  - Production of heparin binding epidermal growth factor-like growth factor in the
      early phase of regeneration after acute renal injury. Isolation and localization
      of bioactive molecules.
AB  - We have recently reported that heparin-binding epidermal growth factor-like
      growth factor (HB-EGF) mRNA is induced in the rat kidney after acute ischemic
      injury. The present studies were designed to investigate whether bioactive HB-EGF
      protein is also produced in response to renal injury induced by either
      ischemia/reperfusion or aminoglycosides. Heparin-binding proteins were purified
      from kidney homogenates by heparin affinity column chromatography using elution
      with a 0.2-2.0 M gradient of NaCl. A single peak of proteins that eluted at 1.0
      1.2 M NaCl was detected in the postischemic kidney within 6 h of injury. This
      eluate fraction stimulated DNA synthesis in quiescent Balb/c3T3, RIE, and NRK-52E
      cell lines, all of which are responsive to the epidermal growth factor family of
      mitogenic proteins. The EGF receptor of A431 cells was also tyrosine
      phosphorylated by this eluate peak. Furthermore, immunoblotting with a polyclonal
      antibody against rat HB-EGF indicated that the eluate peak contained
      immunoreactive proteins of 22 and 29 kD mol wt, consistent with the reported
      sizes of the secreted form and membrane anchored form of HB-EGF, respectively.
      Immunohistochemical studies revealed that HB-EGF was produced predominantly in
      distal tubules in kidneys injured either by ischemia/reperfusion or
      aminoglycoside administration. We also found that during metanephric development
      immunoreactive HB-EGF was detected in the ureteric bud as early as E14.5 and
      persisted in structures arising from the ureteric bud throughout embryogenesis.
      These results suggest that in response to acute injury, HB-EGF is produced
      predominantly in distal tubules and that endogenous HB-EGF may be an important
      growth factor involved in renal epithelial cell repair, proliferation, and
      regeneration in the early stages of recovery after acute renal injury, as well as
      in nephrogenesis.

PMID- 9151786
TI  - Human cytotrophoblasts adopt a vascular phenotype as they differentiate. A
      strategy for successful endovascular invasion?
AB  - Establishment of the human placenta requires that fetal cytotrophoblast stem
      cells in anchoring chorionic villi become invasive. These cytotrophoblasts
      aggregate into cell columns and invade both the uterine interstitium and
      vasculature, anchoring the fetus to the mother and establishing blood flow to the
      placenta. Cytotrophoblasts colonizing spiral arterioles replace maternal
      endothelium as far as the first third of the myometrium. We show here that
      differentiating cytotrophoblasts transform their adhesion receptor phenotype so
      as to resemble the endothelial cells they replace. Cytotrophoblasts in cell
      columns show reduced E-cadherin staining and express VE-(endothelial) cadherin,
      platelet-endothelial adhesion molecule-1, vascular endothelial adhesion molecule
      1, and alpha-4-integrins. Cytotrophoblasts in the uterine interstitium and
      maternal vasculature continue to express these receptors, and, like endothelial
      cells during angiogenesis, also stain for alphaVbeta3. In functional studies,
      alphaVbeta3 and VE-cadherin enhance, while E-cadherin restrains, cytotrophoblast
      invasiveness. Cytotrophoblasts expressing alpha4 integrins bound immobilized VCAM
      1 in vitro, suggesting that this receptor-pair could mediate cytotrophoblast
      endothelium or cytotrophoblast-cytotrophoblast interactions in vivo, during
      endovascular invasion. In the pregnancy disorder preeclampsia, in which
      endovascular invasion remains superficial, cytotrophoblasts fail to express most
      of these endothelial markers (Zhou et al., 1997. J. Clin. Invest. 99:2152-2164.),
      suggesting that this adhesion phenotype switch is required for successful
      endovascular invasion and normal placentation.

PMID- 9151787
TI  - Preeclampsia is associated with failure of human cytotrophoblasts to mimic a
      vascular adhesion phenotype. One cause of defective endovascular invasion in this
      syndrome?
AB  - In human pregnancy, placental cytotrophoblasts that invade the uterus
      downregulate the expression of adhesion receptors that are characteristic of
      their epithelial origin, and upregulate the expression of adhesion receptors that
      are expressed by vascular cells. We suggest that this transformation could be
      critical to endovascular invasion, the process whereby cytotrophoblasts invade
      the uterine spiral arterioles and line their walls (Zhou et al. J. Clin. Invest.
      1997. 99: 2139-2151.). To better understand the in vivo significance of these
      findings, we tested the hypothesis that in preeclampsia, an important disease of
      pregnancy in which endovascular invasion is abrogated, cytotrophoblasts fail to
      adopt a vascular adhesion phenotype. In experiments described here we stained
      placental bed biopsy specimens from age-matched control pregnancies and from
      those complicated by preeclampsia with antibodies that recognize adhesion
      molecules that are normally modulated during this transformation. In
      preeclampsia, differentiating/invading cytotrophoblasts fail to express properly
      many of these molecules, including integrin, cadherin, and Ig superfamily
      members. These results suggest that preeclampsia is associated with failure of
      cytotrophoblasts to mimic a vascular adhesion phenotype. The functional
      consequences of this abnormality are unknown, but are likely to affect negatively
      cytotrophoblast endovascular invasion and uterine arteriole remodeling, thereby
      compromising blood flow to the maternal-fetal interface.

PMID- 9151788
TI  - Homing of mucosal leukocytes to joints. Distinct endothelial ligands in synovium
      mediate leukocyte-subtype specific adhesion.
AB  - Inflammation and infection of the gut can be followed by reactive arthritis at a
      distant joint. Leukocyte recruitment into synovium is essential for this process,
      but nothing is known about the endothelial adhesion molecules in synovial
      membrane which direct the homing of activated, gut-derived leukocytes to joints.
      Here we analyzed the expression of the known endothelial adhesion molecules in
      inflamed synovium and their function in binding of mucosal leukocytes.
      Intercellular adhesion molecule-1 (ICAM-1/CD54) and vascular adhesion protein-1
      (VAP-1) were most prominently expressed in synovial vessels. All other adhesion
      molecules were found at lower levels in inflamed synovia, except mucosal
      addressin which was absent. Binding of macrophages isolated from lamina propria
      of the gut to synovial endothelium was almost entirely P-selectin-dependent. In
      contrast, small intestinal lymphocytes and immunoblasts both relied mainly on VAP
      1 in recognition of synovial vessels. Thus, endothelial P-selectin and VAP-1
      mediate binding of mucosal effector cells to synovium in a leukocyte subtype
      selective manner. Antiadhesive therapy against these inducible molecules should
      ablate the pathogenetic cascade leading to inappropriate homing of leukocytes to
      joints in arthritis.

PMID- 9151789
TI  - Role of the glucosamine pathway in fat-induced insulin resistance.
AB  - To examine whether the hexosamine biosynthetic pathway might play a role in fat
      induced insulin resistance, we monitored the effects of prolonged elevations in
      FFA availability both on skeletal muscle levels of UDP-N-acetyl-hexosamines and
      on peripheral glucose disposal during 7-h euglycemic-hyperinsulinemic
      (approximately 500 microU/ml) clamp studies. When the insulin-induced decrease in
      the plasma FFA levels (to approximately 0.3 mM) was prevented by infusion of a
      lipid emulsion in 15 conscious rats (plasma FFA approximately 1.4 mM), glucose
      uptake (5-7 h = 32.5+/-1.7 vs 0-2 h = 45.2+/-2.8 mg/kg per min; P < 0.01) and
      glycogen synthesis (P < 0.01) were markedly decreased. During lipid infusion,
      muscle UDP-N-acetyl-glucosamine (UDP-GlcNAc) increased by twofold (to 53.4+/-1.1
      at 3 h and to 55.5+/-1.1 nmol/gram at 7 h vs 20.4+/-1.7 at 0 h, P < 0.01) while
      glucose-6-phosphate (Glc-6-P) levels were increased at 3 h (475+/-49 nmol/gram)
      and decreased at 7 h (133+/-7 vs 337+/-28 nmol/gram at 0 h, P < 0.01). To discern
      whether such an increase in the skeletal muscle UDP-GlcNAc concentration could
      account for the development of insulin resistance, we generated similar increases
      in muscle UDP-GlcNAc using three alternate experimental approaches. Euglycemic
      clamps were performed after prolonged hyperglycemia (18 mM, n = 10), or increased
      availability of either glucosamine (3 micromol/kg per min; n = 10) or uridine (30
      micromol/kg per min; n = 4). These conditions all resulted in very similar
      increases in the skeletal muscle UDP-GlcNAc (to approximately 55 nmol/gram) and
      markedly impaired glucose uptake and glycogen synthesis. Thus, fat-induced
      insulin resistance is associated with: (a) decreased skeletal muscle Glc-6-P
      levels indicating defective transport/phosphorylation of glucose; (b) marked
      accumulation of the endproducts of the hexosamine biosynthetic pathway preceding
      the onset of insulin resistance. Most important, the same degree of insulin
      resistance can be reproduced in the absence of increased FFA availability by a
      similar increase in skeletal muscle UDP-N-acetyl-hexosamines. In conclusion, our
      results support the hypothesis that increased FFA availability induces skeletal
      muscle insulin resistance by increasing the flux of fructose-6-phosphate into the
      hexosamine pathway.

PMID- 9151790
TI  - T cell source of type 1 cytokines determines illness patterns in respiratory
      syncytial virus-infected mice.
AB  - Manipulation of the cytokine microenvironment at the time of vaccination can
      influence immune responses to remote challenge, providing a strategy to study the
      molecular pathogenesis of respiratory syncytial virus (RSV) vaccine-enhanced
      disease in the mouse model. Although treatment with antibody against IL-4 or
      recombinant IL-12 (rIL-12) at the time of formalin-inactivated RSV vaccination
      induced a similar shift in the pattern of cytokine mRNA expression upon live
      virus challenge, anti-IL-4 treated mice had increased CD8+ cytotoxic T lymphocyte
      activity and reduced illness compared with rIL-12-treated mice. To define
      effector mechanisms responsible for these patterns, CD4+ and/or CD8+ T
      lymphocytes were selectively depleted in vivo at the time of RSV challenge. In
      rIL-12-treated mice, CD4+ lymphocytes made the largest contribution to IFN-gamma
      mRNA, RSV clearance, and illness, while in anti-IL-4 treated mice, CD8+
      lymphocytes were the major effector. The effector responsible for virus clearance
      also mediated illness, suggesting that efficiency of virus clearance determined
      disease expression. These results demonstrate that the phenotype of effector
      cells involved in the immune response to virus challenge may be a more important
      determinant of disease than patterns of cytokine expression classically assigned
      to Th1 and Th2 lymphocytes.

PMID- 9151791
TI  - Vascular dysfunction induced by elevated glucose levels in rats is mediated by
      vascular endothelial growth factor.
AB  - The purpose of these experiments was to investigate a potential role for vascular
      endothelial growth factor (VEGF) in mediating vascular dysfunction induced by
      increased glucose flux via the sorbitol pathway. Skin chambers were mounted on
      the backs of Sprague-Dawley rats and 1 wk later, granulation tissue in the
      chamber was exposed twice daily for 7 d to 5 mM glucose, 30 mM glucose, or 1 mM
      sorbitol in the presence and absence of neutralizing VEGF antibodies. Albumin
      permeation and blood flow were increased two- to three-fold by 30 mM glucose and
      1 mM sorbitol; these increases were prevented by coadministration of neutralizing
      VEGF antibodies. Blood flow and albumin permeation were increased approximately
      2.5-fold 1 h after topical application of recombinant human VEGF and these
      effects were prevented by nitric oxide synthase (NOS) inhibitors (aminoguanidine
      and N(G)-monomethyl L-arginine). Topical application of a superoxide generating
      system increased albumin permeation and blood flow and these changes were
      markedly attenuated by VEGF antibody and NOS inhibitors. Application of sodium
      nitroprusside for 7 d or the single application of a calcium ionophore, A23187,
      mimicked effects of glucose, sorbitol, and VEGF on vascular dysfunction and the
      ionophore effect was prevented by coadministration of aminoguanidine. These
      observations suggest a potentially important role for VEGF in mediating vascular
      dysfunction induced by "hypoxia-like" cytosolic metabolic imbalances (reductive
      stress, increased superoxide, and nitric oxide production) linked to increased
      flux of glucose via the sorbitol pathway.

PMID- 9151792
TI  - Endogenous endothelins mediate increased distal tubule acidification induced by
      dietary acid in rats.
AB  - We examined if endogenous endothelins mediate the decreased HCO3 secretion and
      increased H+ secretion in in vivo-perfused distal tubules of rats fed dietary
      acid as (NH4)2SO4. Animals given (NH4)2SO4 drinking solution had higher
      endothelin-1 addition to renal interstitial fluid than those given distilled H2O
      (480+/-51 vs. 293+/-32 fmol g kidney wt(-1) min(-1), respectively, P < 0.03).
      (NH4)2SO4-ingesting animals infused with bosentan (10 mg/kg) to inhibit A- and B
      type endothelin receptors had higher HCO3 secretion than baseline (NH4)2SO4
      animals (-4.7+/-0.4 vs. -2.4+/-0.3 pmol mm(-1) min(-1), P < 0.01), but (NH4)2SO4
      animals given a specific inhibitor of A-type endothelin receptors (BQ-123) did
      not (-2.0+/-0.2 pmol mm(-1) min(-1), P = NS vs. baseline). H+ secretion was lower
      in bosentan-infused compared with baseline (NH4)2SO4 animals (27.7+/-2.5 vs.
      43.9+/-4.0 pmol mm(-1) min(-1), P < 0.03), but that for BQ-123-infused (NH4)2SO4
      animals was not (42.9+/-4.2 pmol mm(-1) min(-1), P = NS vs. baseline). Bosentan
      had no effect on distal tubule HCO3 or H+ secretion in control animals. The data
      show that dietary acid increases endothelin-1 addition to renal interstitial
      fluid and that inhibition of B- but not A-type endothelin receptors blunts the
      decreased HCO3 secretion and increased H+ secretion in the distal tubule of
      animals given dietary acid. The data are consistent with endogenous endothelins
      as mediators of increased distal tubule acidification induced by dietary acid.

PMID- 9151793
TI  - Increased blood pressure in rats after long-term inhibition of the neuronal
      isoform of nitric oxide synthase.
AB  - In the kidney, nitric oxide synthase (NOS) of the neuronal isoform (nNOS) is
      predominantly located in the macula densa cells. Unspecific chronic NOS
      inhibition in rats leads to elevated blood pressure (P(A)), associated with
      increased renal vascular resistance. This study was designed to examine the
      effect of chronic selective inhibition of nNOS with 7-nitro indazole (7-NI) on
      P(A), GFR, and the tubuloglomerular feedback (TGF) system. P(A) was repeatedly
      measured by a noninvasive tail-cuff technique for 4 wk in rats treated orally
      with 7-NI, and in control rats. After treatment, the animals were anesthetized
      and renal excretion rates, GFR, and TGF activity were determined. After 1 wk of 7
      NI treatment P(A) was increased from 129+/-4 to 143 2 mmHg. GFR (1.85+/-0.1 vs.
      1.97+/-0.2 ml/min in controls) was unchanged, but micropuncture studies revealed
      a more sensitive TGF than in controls. After 4 wk of 7-NI treatment P(A) was
      152+/-4 mmHg, but no change in GFR (1.90+/-0.5 ml/min) or TGF sensitivity was
      detected. Acute administration of 7-NI to nontreated rats did not affect P(A),
      but decreased GFR (1.49+/-0.1 ml/min) and increased TGF sensitivity. In
      conclusion, chronic nNOS inhibition leads to increased P(A). Our results suggest
      that the elevated P(A) could be caused by an initially increased TGF sensitivity,
      leading to decreased GFR and an increased body fluid volume.

PMID- 9151794
TI  - Mechanism of impaired insulin-stimulated muscle glucose metabolism in subjects
      with insulin-dependent diabetes mellitus.
AB  - To determine the mechanism of impaired insulin-stimulated muscle glycogen
      metabolism in patients with poorly controlled insulin-dependent diabetes mellitus
      (IDDM), we used 13C-NMR spectroscopy to monitor the peak intensity of the C1
      resonance of the glucosyl units in muscle glycogen during a 6-h hyperglycemic
      hyperinsulinemic clamp using [1-(13)C]glucose-enriched infusate followed by
      nonenriched glucose. Under similar steady state (t = 3-6 h) plasma glucose
      (approximately 9.0 mM) and insulin concentrations (approximately 400 pM),
      nonoxidative glucose metabolism was significantly less in the IDDM subjects
      compared with age-weight-matched control subjects (37+/-6 vs. 73+/-11 micromol/kg
      of body wt per minute, P < 0.05), which could be attributed to an approximately
      45% reduction in the net rate of muscle glycogen synthesis in the IDDM subjects
      compared with the control subjects (108+/-16 vs. 195+/-6 micromol/liter of muscle
      per minute, P < 0.001). Muscle glycogen turnover in the IDDM subjects was
      significantly less than that of the controls (16+/-4 vs. 33+/-5%, P < 0.05),
      indicating that a marked reduction in flux through glycogen synthase was
      responsible for the reduced rate of net glycogen synthesis in the IDDM subjects.
      31P-NMR spectroscopy was used to determine the intramuscular concentration of
      glucose-6-phosphate (G-6-P) under the same hyperglycemic-hyperinsulinemic
      conditions. Basal G-6-P concentration was similar between the two groups
      (approximately 0.10 mmol/kg of muscle) but the increment in G-6-P concentration
      in response to the glucose-insulin infusion was approximately 50% less in the
      IDDM subjects compared with the control subjects (0.07+/-0.02 vs. 0.13+/-0.02
      mmol/kg of muscle, P < 0.05). When nonoxidative glucose metabolic rates in the
      control subjects were matched to the IDDM subjects, the increment in the G-6-P
      concentration (0.06+/-0.02 mmol/kg of muscle) was no different than that in the
      IDDM subjects. Together, these data indicate that defective glucose
      transport/phosphorylation is the major factor responsible for the lower rate of
      muscle glycogen synthesis in the poorly controlled insulin-dependent diabetic
      subjects.

PMID- 9151795
TI  - Treatment with depleting CD4 monoclonal antibody results in a preferential loss
      of circulating naive T cells but does not affect IFN-gamma secreting TH1 cells in
      humans.
AB  - CD4(pos) TH1 T cells are considered to play a central role in a number of human
      autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis.
      Experimental treatment protocols aimed at selectively eliminating CD4(pos) T
      cells thus far have yielded disappointing clinical results. Here we analyzed
      phenotype and function of circulating T cells in multiple sclerosis patients
      treated with the chimeric CD4 mAb cM-T412 in a randomized, double-blind, placebo
      controlled, magnetic resonance imaging-monitored phase II trial. Treatment
      resulted in a long-lasting depletion of CD4(pos) T cells but did not affect
      CD8(pos) T cell numbers. Analysis of CD4(pos) subpopulations showed that
      unprimed, CD45RA(pos)/R0(neg) lymphocytes were approximately three times more
      sensitive to the mAb than primed, CD45RA(neg)/R0(pos) T cells. Notably, within
      the CD45RA(pos) subset, T cells with phenotypic evidence of prior activation,
      i.e., expressing Fas, were relatively insensitive to cM-T412, compared with
      Fas(neg) cells. Remarkably, while a decrease in the number of IL-4-producing T
      helper 2 (TH2)-type cells in the anti-CD4 treated group was observed, numbers of
      IFN-gamma-producing T helper 1 (TH1)-type cells remained stable, resulting in a
      significant increase in the TH1/TH2 ratio. Our data show that treatment with
      depleting CD4 mAb does not eliminate the cells most strongly involved in the
      disease process, i.e., primed, IFN-gamma-producing TH1-type cells, and may
      therefore give an explanation for the lack of beneficial clinical effects of
      depleting CD4 mAb in human chronic autoimmune disease.

PMID- 9151796
TI  - Scott syndrome erythrocytes contain a membrane protein capable of mediating Ca2+
      dependent transbilayer migration of membrane phospholipids.
AB  - Phospholipid (PL) scramblase is a plasma membrane protein that mediates
      accelerated transbilayer migration of PLs upon binding Ca2+, facilitating rapid
      mobilization of phosphatidylserine to the cell surface upon elevation of internal
      Ca2+. In patients with Scott syndrome, a congenital bleeding disorder related to
      defective expression of membrane coagulant activity, circulating blood cells show
      decreased cell surface exposure of phosphatidylserine at elevated cytosolic
      [Ca2+], implying an underlying defect or deficiency of PL scramblase. To gain
      insight into the molecular basis of this disorder, we compared PL scramblase in
      Scott erythrocyte membranes to those of normal controls. Whereas membranes of
      Scott cells were unresponsive to Ca2+-induced activation of PL scramblase at
      neutral pH, apparently normal PL scramblase activity was induced at pH < 6.0.
      After extraction with octylglucoside, a membrane protein was isolated from the
      Scott cells which exhibited normal PL scramblase activity when reconstituted in
      vesicles with exogenous PLs. Like PL scramblase from normal erythrocytes, PL
      scramblase from Scott erythrocytes was maximally activated either by addition of
      Ca2+ (at pH 7.4) or by acidification to pH < 6.0, and similar apparent affinities
      for Ca2+ and rates of transbilayer transfer of PLs were observed. This suggests
      that the defect in Scott syndrome is related to an altered interaction of Ca2+
      with PL scramblase on the endofacial surface of the cell membrane, due either to
      an intrinsic constraint upon the protein preventing interaction with Ca2+ in
      situ, or due to an unidentified inhibitor or cofactor in the Scott cell that is
      dissociated by detergent.

PMID- 9151797
TI  - Growth hormone and bile acid synthesis. Key role for the activity of hepatic
      microsomal cholesterol 7alpha-hydroxylase in the rat.
AB  - Growth hormone (GH) has an important role in the regulation of hepatic LDL
      receptor expression and plasma lipoprotein levels. This investigation was
      undertaken to characterize the effects of GH on hepatic cholesterol and bile acid
      metabolism in the rat. In hypophysectomized (Hx) rats, the activities of the rate
      limiting enzymes in cholesterol and bile acid biosynthesis, 3-hydroxy-3
      methylglutaryl coenzyme A reductase (HMG CoA reductase) and cholesterol 7alpha
      hydroxylase (C7alphaOH), were reduced by 71 and 64%, respectively. HMG CoA
      reductase mRNA levels were reduced by 37%, whereas C7alphaOH mRNA was increased
      by 81%. LDL receptor expression was reduced by 18% in Hx rats, without any change
      in the LDL receptor mRNA levels. Although the normal diurnal variation of
      C7alphaOH activity was preserved in Hx rats, the activity of C7alphaOH was much
      reduced both at midday and midnight. Total hepatic cholesterol was increased by
      14% in Hx animals whereas microsomal cholesterol was unchanged. The rate of
      cholesterol esterification was enhanced (by 38%) in liver microsomes from Hx
      rats. Stepwise hormonal substitution of Hx rats showed that GH, but not thyroid
      hormone or cortisone, was essential to normalize the enzymatic activity of
      C7alphaOH. GH also normalized the altered plasma lipoprotein pattern in Hx rats,
      and increased the fecal output of bile acids. The latter effect was particularly
      evident when GH was combined with cortisone and thyroid hormone. Also in normal
      rats, GH stimulated C7alphaOH activity. In conclusion, GH has an essential role
      to maintain a normal enzymatic activity of C7alphaOH, and this, at least in part,
      explains the effects of GH on hepatic cholesterol metabolism. GH is also of
      critical importance to normalize the altered plasma lipoprotein pattern in Hx
      rats.

PMID- 9151798
TI  - Leukocyte adhesion in angiogenic blood vessels. Role of E-selectin, P-selectin,
      and beta2 integrin in lymphotoxin-mediated leukocyte recruitment in tumor
      microvessels.
AB  - Interaction of circulating leukocytes with tumor microvasculature is a critical
      event in the recruitment of effector cells into the tumor stroma. We have
      examined the ability of lymphotoxin (TNF-beta), to stimulate rolling, adhesion,
      and transmigration of leukocytes in angiogenic blood vessels induced by tumor
      spheroids of Lewis lung carcinoma (LLC) implanted in dorsal skinfold chambers of
      nude mice. In the absence of cytokine stimulation, circulating leukocytes failed
      to appreciably interact with tumor microvessels (TMV), although significant
      rolling and adhesion was observed in normal vessels. However, stimulation with
      lymphotoxin (LT) resulted in a rapid increase in the number of fast and slow
      rolling leukocytes in TMV. Treatment with anti-P-selectin mAb 5H1 resulted in
      inhibition of fast rollers alone, while combination treatment with anti-P
      selectin and anti-E-selectin (9A9) mAbs effectively blocked slow rolling of
      leukocytes. Superfusion of the lymphotoxin-stimulated neovasculature with
      leukotriene B4 (LTB4) resulted in stable cell adhesion followed by emigration of
      leukocytes into the tumor stroma. LTB4-mediated adhesion and transmigration was
      significantly inhibited by treatment with anti-beta2 mAb 2E6. These studies
      delineate a multistep cascade of leukocyte adhesion in TMV and demonstrate that
      stimulation of the neovasculature with cytokines and chemoattractants can result
      in P- and E-selectin-dependent rolling and beta2-dependent stable adhesion
      followed by transmigration into the tumor stroma.

PMID- 9151799
TI  - Inhibition of human colon cancer cell growth by selective inhibition of
      cyclooxygenase-2.
AB  - A considerable amount of evidence collected from several different experimental
      systems indicates that cyclooxygenase-2 (COX-2) may play a role in colorectal
      tumorigenesis. Large epidemiologic studies have shown a 40-50% reduction in
      mortality from colorectal cancer in persons taking aspirin or other nonsteroidal
      antiinflammatory drugs on a regular basis. One property shared by all of these
      drugs is their ability to inhibit COX, a key enzyme in the conversion of
      arachidonic acid to prostaglandins. Two isoforms of COX have been characterized,
      COX-1 and COX-2. COX-2 is expressed at high levels in intestinal tumors in humans
      and rodents. In this study, we selected two transformed human colon cancer cell
      lines for studies on the role of COX-2 in intestinal tumorigenesis. We evaluated
      HCA-7 cells which express high levels of COX-2 protein constitutively and HCT-116
      cells which lack COX-2 protein. Treatment of nude mice implanted with HCA-7 cells
      with a selective COX-2 inhibitor (SC-58125), reduced tumor formation by 85-90%.
      SC-58125 also inhibited colony formation of cultured HCA-7 cells. Conversely, SC
      58125 had no effect on HCT-116 implants in nude mice or colony formation in
      culture. Here we provide evidence that there may be a direct link between
      inhibition of intestinal cancer growth and selective inhibition of the COX-2
      pathway.

PMID- 9151800
TI  - Anti-beta2-glycoprotein I (beta2GPI) monoclonal antibodies with lupus
      anticoagulant-like activity enhance the beta2GPI binding to phospholipids.
AB  - beta2-Glycoprotein I (beta2GPI), a plasma glycoprotein with phospholipid-binding
      property, is known to be the actual target antigen for autoimmune type
      anticardiolipin antibodies (aCLs). Certain groups of aCLs (anti-beta2GPI
      antibodies) exert lupus anticoagulant (LA) activity and perturb the function of
      vascular endothelial cells. This investigation aimed at highlighting some
      insights into the molecular basis by which aCLs exert their biological effects by
      using anti-beta2GPI mAbs with well-characterized epitopes from mice and from
      patients with antiphospholipid syndrome. Anti-beta2GPI mAbs directed against the
      third domain (Cof-20 and Cof-22) and fourth domain (Cof-21, EY1C8, and EY2C9) of
      beta2GPI inhibited the thrombin generation induced by Russell's viper venom in
      diluted plasma and that induced by the prothrombinase complex reconstituted with
      purified clotting factors. This anticoagulant activity was abrogated in the
      presence of an excess amount of phospholipids, thus resembling the LA activity.
      In stark contrast, anti-beta2GPI mAbs directed against the fifth domain and the
      carboxy-terminal region of the fourth domain showed no LA-like activity. These
      findings suggest that the LA activity of anti-beta2GPI antibodies depends on
      their epitope specificity. Experiments carried out to clarify the mechanism of
      the LA activity showed that anti-beta2GPI mAbs with LA-like activity, but not
      those without this effect, enhance the beta2GPI binding to phospholipids. In
      addition, the F(ab')2 fragment, but not the Fab' fragment, of the anti-beta2GPI
      mAbs was found to enhance the LA activity and the beta2GPI binding to
      phospholipids, suggesting that anti-beta2GPI antibodies induce formation of
      multiple complexes of beta2GPI on the surface of phospholipids because of their
      bivalent property. This clustering of beta2GPI molecules induced by anti-beta2GPI
      antibodies, probably because of their multivalent property and epitope
      specificity, might hinder the lateral mobility and activation of clotting factors
      on the surface of phospholipids and thus exert LA activity. Clustering of
      beta2GPI molecules may also explain the molecular mechanism by which anti
      beta2GPI antibodies alter the function of leukocytes and endothelial cells. The
      well-documented heterogeneous LA activity of aCLs (anti-beta2GPI antibodies) may
      also be explained by their epitope specificity.

PMID- 9151801
TI  - Sib-pair analysis detects elevated Lp(a) levels and large variation of Lp(a)
      concentration in subjects with familial defective ApoB.
AB  - Whether or not Lp(a) plasma levels are affected by the apoB R3500Q mutation,
      which causes Familial Defective apoB (FDB), is still a matter of debate. We have
      analyzed 300 family members of 13 unrelated Dutch index patients for the apoB
      mutation and the apolipoprotein(a) [apo(a)] genotype. Total cholesterol, LDL
      cholesterol, and lipoprotein(a) [Lp(a)] concentrations were determined in 85 FDB
      heterozygotes and 106 non-FDB relatives. Mean LDL levels were significantly
      elevated in FDB subjects compared to non-FDB relatives (P < 0.001). Median Lp(a)
      levels were not different between FDB subjects and their non-FDB relatives. In
      contrast, sib-pair analysis demonstrated a significant effect of the FDB status
      on Lp(a) levels. In sib pairs identical by descent for apo(a) alleles but
      discordant for the FDB mutation (n = 11) each sib with FDB had a higher Lp(a)
      level than the corresponding non-FDB sib. Further, all possible sib pairs (n =
      105) were grouped into three categories according to the absence/presence of the
      apoB R3500Q mutation in one or both subjects of a sib pair. The variability of
      differences in Lp(a) levels within the sib pairs increased with the number (0, 1,
      and 2) of FDB subjects present in the sib pair. This suggests that the FDB status
      increases Lp(a) level and variability, and that apoB may be a variability gene
      for Lp(a) levels in plasma.

PMID- 9151802
TI  - The midcycle increase in ovarian glucose uptake is associated with enhanced
      expression of glucose transporter 3. Possible role for interleukin-1, a putative
      intermediary in the ovulatory process.
AB  - This study characterizes the rat ovary as a site of hormonally dependent glucose
      transporter (Glut) expression, and explores the potential role of interleukin
      (IL)-1, a putative intermediary in the ovulatory process, in this regard.
      Molecular probing throughout a simulated estrous cycle revealed a significant
      surge in ovarian Glut3 (but not Glut1) expression at the time of ovulation.
      Treatment of cultured whole ovarian dispersates from immature rats with IL-1beta
      resulted in upregulation of the relative abundance of the Glut1 (4.5-fold) and
      Glut3 (3.5-fold) proteins as determined by Western blot analysis. Other members
      of the Glut family (i.e., Gluts 2, 4, and 5) remained undetectable. The ability
      of IL-1 to upregulate Glut1 and Glut3 transcripts proved time-, dose-, nitric
      oxide-, and protein biosynthesis-dependent but glucose independent. Other ovarian
      agonists (i.e., TNF alpha, IGF-I, interferon-gamma, and insulin) were without
      effect. Taken together, our findings establish the mammalian ovary as a site of
      cyclically determined Glut1 and Glut3 expression, and disclose the ability of IL
      1 to induce the ovarian expression as well as translation of Glut1 and Glut3 (but
      not of Gluts 2, 4, or 5). Our observations also establish IL-1 as the first known
      regulator of Glut3, the most efficient Glut known to date. In so doing, IL-1, a
      putative component of the ovulatory process, may be acting to meet the increased
      metabolic demands imposed on the growing follicle and the ovulated cumulus
      enclosed oocyte.

PMID- 9151803
TI  - A peptidomimetic antagonist of the alpha(v)beta3 integrin inhibits bone
      resorption in vitro and prevents osteoporosis in vivo.
AB  - Osteoclastic bone degradation requires intimacy between the matrix and the
      resorptive cell. While the precise role the integrin alpha(v)beta3 plays in the
      process is not yet understood, occupancy of the heterodimer by soluble ligand or
      by blocking antibody effectively inhibits bone resorption in vitro and in vivo,
      suggesting that alpha(v)beta3 blockade may prevent postmenopausal osteoporosis.
      Thus, we identified a synthetic chemical peptide mimetic, beta-[2-[[5
      [(aminoiminomethyl)amino]-1-oxopentyl]amino]-1-+ ++oxoethyl]amino-3
      pyridinepropanoic acid, bistrifluoroacetate (SC56631) based upon the
      alpha(v)beta3 ligand, Arg-Gly-Asp (RGD), which recognizes the isolated integrin,
      and its relative, alpha(v)beta5, as effectively as does the natural peptide. The
      mimetic dampens osteoclastic bone resorption in vitro and in vivo. Most
      importantly, intravenous administration of the mimetic prevents the 55% loss of
      trabecular bone sustained by rats within 6 wk of oophorectomy. Histological
      examination of bones taken from SC56631-treated, oophorectomized animals also
      demonstrates the compound's bone sparing properties and its capacity to decrease
      osteoclast number. Thus, an RGD mimetic prevents the rapid bone loss that
      accompanies estrogen withdrawal.

PMID- 9151804
TI  - Cell-homologous genes in the Kaposi's sarcoma-associated rhadinovirus human
      herpesvirus 8: determinants of its pathogenicity?

PMID- 9151805
TI  - The cyclin encoded by Kaposi's sarcoma-associated herpesvirus stimulates cdk6 to
      phosphorylate the retinoblastoma protein and histone H1.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8) is a novel
      gammaherpesvirus implicated in the cause of Kaposi's sarcoma and certain
      malignancies of lymphatic origin. One of the candidate genes possibly involved in
      promoting tumor development is an open reading frame (ORF) with sequence
      similarity to human type D cyclin genes. This cyclin-like gene, when expressed in
      tissue culture cells, promotes phosphorylation and inactivation of the
      retinoblastoma tumor suppressor protein and thereby may result in deregulation of
      cell division control. We report here the biochemical characterization of this
      cyclin (KSHV-cyc) and the kinase activity that it elicits upon expression in
      tissue culture cells. We demonstrate that the kinase activity associated with
      KSHV-cyc is sensitive to the cdk inhibitor p27 (KIP) and due to activation of
      cdk6. However, in contrast to cdk6 activated by cellular type D cyclins, the cdk6
      activated by KSHV-cyc is capable of phosphorylating not only the retinoblastoma
      protein but also histone H1. This finding implies that activation by KSHV-cyc
      alters the substrate preference of this cdk. This may have important
      physiological consequences in that the kinase activity triggered by this viral
      cyclin may abrogate cell cycle checkpoints in addition to those targeted by
      cellular cyclin D-cdk6 kinase.

PMID- 9151807
TI  - Circularization and cleavage of guinea pig cytomegalovirus genomes.
AB  - The mechanisms by which herpesvirus genome ends are fused to form circles after
      infection and are re-formed by cleavage from concatemeric DNA are unknown. We
      used the simple structure of guinea pig cytomegalovirus genomes, which have
      either one repeated DNA sequence at each end or one repeat at one end and no
      repeat at the other, to study these mechanisms. In circular DNA, two restriction
      fragments contained fused terminal sequences and had sizes consistent with the
      presence of single or double terminal repeats. This result implies a simple
      ligation of genomic ends and shows that circularization does not occur by
      annealing of single-stranded terminal repeats formed by exonuclease digestion.
      Cleavage to form the two genome types occurred at two sites, and homologies
      between these sites identified two potential cis elements that may be necessary
      for cleavage. One element coincided with the A-rich region of a pac2 sequence and
      had 9 of 11 bases identical between the two sites. The second element had six
      bases identical at both sites, in each case 7 bp from the termini. To confirm the
      presence of cis cleavage elements, a recombinant virus in which foreign sequences
      displaced the 6- and 11-bp elements 1 kb from the cleavage point was constructed.
      Cleavage at the disrupted site did not occur. In a second recombinant virus,
      restoration of 64 bases containing the 6- and 11-bp elements to the disrupted
      cleavage site restored cleavage. Therefore, cis cleavage elements exist within
      this 64-base region, and sequence conservation suggests that they are the 6- and
      11-bp elements.

PMID- 9151806
TI  - The herpes simplex virus type 1 2.0-kilobase latency-associated transcript is a
      stable intron which branches at a guanosine.
AB  - We have used a minigene construct of the herpes simplex virus type 1 (HSV-1)
      latency-associated transcript (LAT) gene to analyze its transcripts in transient
      transfection assays. A 2.8-kb fragment of the approximately 8.5-kb LAT gene
      encompassing the 2.0-kb LAT was cloned into a eukaryotic expression vector
      downstream of the cytomegalovirus immediate-early gene promoter. Northern
      hybridization of RNA isolated from transfected COS-1 cells identified three LAT
      specific transcripts, 3.4, 2.0, and 1.4 kb in size. Mapping of these transcripts
      by Northern hybridization indicated that the 1.4- and 2.0-kb RNAs are
      nonoverlapping, while the 3.4-kb RNA overlaps both smaller RNAs. Reverse
      transcription-PCR (RT-PCR) and partial sequencing of the 1.4-kb RNA revealed that
      this RNA is the spliced exons of the 3.4-kb primary transcript. The 2.0-kb LAT
      appears to be an intron accumulating after splicing of the minor LAT (mLAT) pre
      mRNA. The splice donor and acceptor sites for the 2.0-kb LAT identified in
      transfected and HSV-1-infected cells are identical. Mapping of the branch point
      of this intron by RT-PCR in transfected and HSV-1-infected cells, as well as in
      latently infected murine trigemial ganglia, shows that it is a guanosine. This
      branch site does not bear homology to consensus mammalian branch site sequences.
      These data provide evidence that the 2.0-kb LAT is an intron of the mLAT pre-mRNA
      with a unique branch point.

PMID- 9151808
TI  - Characterization of molecularly cloned simian-human immunodeficiency viruses
      causing rapid CD4+ lymphocyte depletion in rhesus monkeys.
AB  - In vivo passage of a chimeric simian-human immunodeficiency virus (SHIV-89.6)
      expressing the human immunodeficiency virus type 1 (HIV-1) tat, rev, vpu, and env
      genes generated pathogenic viruses (SHIV-89.6P) inducing rapid CD4+ lymphocyte
      depletion and AIDS-like illness in rhesus monkeys (K. Reimann, J. T. Li, R.
      Veazey, M. Halloran, I.-W. Park, G. B. Karlsson, J. Sodroski, and N. L. Letvin,
      J. Virol. 70:6922-6928, 1996). To characterize the molecular changes responsible
      for this increase in virulence, infectious proviral clones of SHIV-89.6P isolates
      were derived. Viruses generated from some of these clones caused a rapid and
      profound decline of CD4+ lymphocytes in a high percentage of inoculated monkeys.
      Nucleotide changes potentially responsible for the increased virulence of SHIV
      89.6P were limited to the env, tat, or long terminal repeat sequences, with most
      of the observed changes in env. Nucleotide changes in env altered 12 amino acids
      in the gp120 and gp41 exterior domains, and a 140-bp deletion in env resulted in
      the substitution of the carboxyl terminus of the SIVmac gp41 glycoprotein for
      that of the HIV-1 gp41 glycoprotein. The availability of pathogenic proviral
      clones should facilitate dissection of the molecular determinants of SHIV-89.6P
      virulence.

PMID- 9151809
TI  - Activation of endothelial cells via antibody-enhanced dengue virus infection of
      peripheral blood monocytes.
AB  - Although endothelial cells have been speculated to be a target in the
      pathogenesis of dengue hemorrhagic fever (DHF), there has been little evidence
      linking dengue virus infection to any alteration in endothelial cell function. In
      this study, we show that human umbilical vein endothelial cells become activated
      when exposed to culture fluids from dengue virus-infected peripheral blood
      monocytes. Maximum activation was achieved with culture fluids from monocytes in
      which virus infection was enhanced by the addition of dengue virus-immune serum,
      thus correlating with epidemiological evidence that prior immunity to dengue
      virus is a major risk factor for DHF. Activation was strongest for endothelial
      cell expression of VCAM-1 and ICAM-1. In contrast, activation of endothelial cell
      E-selectin expression appeared to be more transient, as indicated by its
      detection at 3 h, but not at 16 h, of treatment. Treatment of monocyte culture
      fluids with anti-tumor necrosis factor alpha (TNF-alpha) antibody largely
      abolished the activation effect (as measured by endothelial cell expression of
      ICAM-1), whereas treatment with IL-1beta receptor antagonist had a much smaller
      inhibitory effect on activation. Endothelial cells inoculated directly with
      dengue virus or with virus-antibody combinations were poorly infectable (compared
      to Vero cells or peripheral blood monocytes), and virus-inoculated endothelial
      cells showed no increased expression of VCAM-1, ICAM-1, or E-selectin. Taken
      together, the results strongly indicate that dengue virus can modulate
      endothelial cell function by an indirect route, in which a key intermediary is
      TNF-alpha released from virus-infected monocytes.

PMID- 9151810
TI  - Genetic drift can dominate short-term human immunodeficiency virus type 1 nef
      quasispecies evolution in vivo.
AB  - The evolution of human immunodeficiency virus (HIV) type 1 nef quasispecies in a
      patient clonally infected with a contaminated batch of blood clotting factor IX
      was monitored. nef sequences were derived at 11, 25, and 41 months postinfection
      from infected peripheral blood mononuclear cells after molecular cloning of PCR
      amplified proviral DNA. The phylogenetic relationships among a total of 41
      informative sequences were established by split decomposition analysis and used
      as a basis to establish a substitution matrix and to score synonymous (s) and
      nonsynonymous (ns) substitutions. The number of observed in-phase stop codons
      within the nef sequences was comparable to that expected on a random basis.
      Similarly, the numbers of observed s and ns substitutions did not differ
      significantly from expected values. No codon position was preferentially mutated.
      The maximum sequence divergence increased in a linear manner, with approximately
      4.4 nucleotide and approximately 3.2 amino acid changes per year. It appears that
      stochastic processes strongly influence short-term HIV nef quasispecies evolution
      in vivo.

PMID- 9151811
TI  - Genetic diversity of feline immunodeficiency virus: dual infection,
      recombination, and distinct evolutionary rates among envelope sequence clades.
AB  - For the rapid genetic analysis of feline immunodeficiency virus (FIV), we
      developed a heteroduplex mobility assay (HMA) that utilizes a PCR-amplified
      fragment of the FIV envelope gene spanning the third and fourth variable regions
      of the envelope surface protein coding sequence. Viral sequences were
      successfully amplified from blood specimens from 98 naturally infected cats from
      Australia, Canada, Germany, Italy, South Africa, and the United States. Eighty
      were clearly assignable to the A or B envelope sequence subtypes. Three belonged
      to subtype C, one was dually infected with viruses harboring the A and B env
      subtypes, and several were categorized as outliers to any of the established
      subtypes or as probable intersubtype recombinants. Some geographic clustering was
      evident, with subtypes A and B found in greater frequency in the western and
      eastern regions of the United States, respectively. Subtypes A, B, and C were
      found on more than one continent, and countries with more than two samples
      analyzed contained at least two subtypes. The broadest representation of subtypes
      was found in Munich, Germany, where three subtypes and one virus that was not
      classifiable by HMA were found. Thirteen samples were selected for DNA sequence
      determination over the same region of env used for HMA. Analysis of all available
      FIV env sequences from this and previous studies revealed the existence of
      recombinant viruses generated from subtype A/B, B/D, and A/C envelope gene
      sequences. Subtype A env sequences were less diverse than subtype B sequences,
      although both groups had well-supported clusters. Furthermore, the mutational
      pattern giving rise to diversification in the two subtypes differed, with the
      subtype A viruses showing half as many synonymous site mutations compared to
      subtype B yet showing similar levels of nonsynonymous site changes. These results
      are consistent with the hypothesis that FIV-B is an older virus group and is
      possibly more host adapted than FIV-A.

PMID- 9151812
TI  - The antiretrovirus drug 3'-azido-3'-deoxythymidine increases the retrovirus
      mutation rate.
AB  - It was previously observed that the nucleoside analog 5-azacytidine increased the
      spleen necrosis virus (SNV) mutation rate 13-fold in one cycle of retrovirus
      replication (V. K. Pathak and H. M. Temin, J. Virol. 66:3093-3100, 1992). Based
      on this observation, we hypothesized that nucleoside analogs used as antiviral
      drugs may also increase retrovirus mutation rates. We sought to determine if 3'
      azido-3'-deoxythymidine (AZT), the primary treatment for human immunodeficiency
      virus type 1 (HIV-1) infection, increases the retrovirus mutation rate. Two
      assays were used to determine the effects of AZT on retrovirus mutation rates.
      The strategy of the first assay involved measuring the in vivo rate of
      inactivation of the lacZ gene in one replication cycle of SNV- and murine
      leukemia virus-based retroviral vectors. We observed 7- and 10-fold increases in
      the SNV mutant frequency following treatment of target cells with 0.1 and 0.5
      microM AZT, respectively. The murine leukemia virus mutant frequency increased
      two- and threefold following treatment of target cells with 0.5 and 1.0 microM
      AZT, respectively. The second assay used an SNV-based shuttle vector containing
      the lacZ alpha gene. Proviruses were recovered as plasmids in Escherichia coli,
      and the rate of inactivation of lacZ alpha was measured. The results indicated
      that treatment of target cells increased the overall mutation rate two- to
      threefold. DNA sequence analysis of mutant proviruses indicated that AZT
      increased both the deletion and substitution rates. These results suggest that
      AZT treatment of HIV-1 infection may increase the degree of viral variation and
      alter virus evolution or pathogenesis.

PMID- 9151813
TI  - Expression and purification of vesicular stomatitis virus N-P complex from
      Escherichia coli: role in genome RNA transcription and replication in vitro.
AB  - The nucleocapsid protein (N) and phosphoprotein (P) genes of vesicular stomatitis
      virus (VSV), Indiana serotype, were coexpressed in Escherichia coli BL21(DE3) by
      using the expression vector pET-3a. The coexpression resulted in the formation of
      N-P complex. The purified N-P complex was found to inhibit transcription in vitro
      mediated by viral ribonucleoprotein (RNP) complex in a dose-dependent manner.
      However, addition of uninfected mammalian cell extracts together with the N-P
      complex to the transcribing RNP resulted in the synthesis of full-length negative
      strand genome RNA. These results indicate that the N-P complex regulated
      transcription and a cellular factor(s) in combination with the N-P complex may
      switch the RNA polymerase from transcription to replication mode.

PMID- 9151814
TI  - An infectious clone of human parainfluenza virus type 3.
AB  - A full-length clone of the human parainfluenza virus type 3 (HPIV-3) genome
      (called pHPIV-3) was constructed, and recombinant, infectious HPIV-3 was
      generated by transfecting pHPIV-3 and support plasmids encoding the HPIV-3 NP, P,
      and L proteins into HeLa cells infected with a vaccinia virus recombinant which
      expresses T7 RNA polymerase. T7 RNA polymerase promoters on the transfected
      plasmids direct the synthesis of transcripts encoding the NP, P, and L proteins
      and a full-length, positive-sense copy of the HPIV-3 genome. Generation of virus
      was dependent on transfection of pHPIV-3 and the HPIV-3 P- and L-encoding
      plasmids. However, a plasmid encoding the NP protein was not required since NP
      was expressed from pHPIV-3. Recovered virus was neutralized by anti-HPIV-3
      antisera and shown to contain specific base substitutions characteristic of pHPIV
      3. Recombination was shown to occur during recovery, as viruses with two distinct
      genotypes and phenotypes were isolated. The ability to produce infectious HPIV-3
      engineered to contain specific alterations within the HPIV-3 genes and cis-acting
      elements expedites the study of all aspects of the virus replication cycle.
      Additionally, analysis of mutations may lead to the identification of attenuating
      genotypes, a key step in the development of a live virus vaccine.

PMID- 9151815
TI  - Pathological changes in the spleens of gamma interferon receptor-deficient mice
      infected with murine gammaherpesvirus: a role for CD8 T cells.
AB  - Murine gammaherpesvirus is a natural rodent pathogen which causes a primary
      infection in the lungs and establishes a persistent infection in B lymphocytes.
      During the primary infection, large amounts of gamma interferon (IFN-gamma) are
      produced by spleen, mediastinal, and cervical lymph node cells. To investigate
      the role of IFN-gamma in control of the virus infection, mice lacking the
      cellular receptor for IFN-gamma (IFN-gamma R-/- mice) were infected with murine
      gammaherpesvirus 68 (MHV68). IFN-gamma R-/- mice showed no difference from wild
      type mice in the titers of infectious virus in the lungs or in the rate of
      clearance of the lung infection. In the spleen, however, clear differences were
      observed. By 14 days postinfection, spleens from IFN-gamma R-/- mice were pale,
      shrunken, and fibrous. Histological examination showed that there was an early
      (day 10) infiltration of granulocytes followed by widespread destruction of
      splenic architecture (days 14 to 17). A marked decrease in the number of splenic
      B cells and CD4+ and CD8+ T cells occurred. These changes were accompanied by a
      10- to 100-fold greater load of latently infected cells in IFN-gamma R-/- mice
      than in wild-type mice at 14 to 17 days postinfection, but this was reduced to
      the levels found in wild-type mice by 21 days postinfection. Treatment of the
      mice with the antiviral drug 2'-deoxyl-5-ethyl-beta-4'-thiouridine from 6 days
      postinfection did not prevent the occurrence of these changes. The changes were,
      however, completely reversed by depletion of CD8+ T cells prior to and during the
      primary infection. Depletion of CD4+ T cells also reversed the major pathological
      and virological changes, although in this case there was evidence of some
      histological changes. Thus, the lack of IFN-gamma receptor had profound
      consequences in spleens of MHV68-infected mice. The possible mechanisms involved
      in these changes are discussed.

PMID- 9151817
TI  - Virion swelling is not required for cotranslational disassembly of cowpea
      chlorotic mottle virus in vitro.
AB  - The mechanism by which virions of cowpea chlorotic mottle virus (CCMV)
      disassemble and allow for translation of the virion RNA is not well understood.
      Previous models have suggested that virion swelling is required to expose the
      virion RNA for translation in a process referred to as cotranslational
      disassembly (M. Brisco, R. Hull, and T. M. A. Wilson, Virology 148:210-217, 1986;
      J. W. Roenhorst, J. W. M. van Lent, and B. J. M. Verduin, Virology 164:91-98,
      1988; J. W. Roenhorst, J. M. Verduin, and R. W. Goldbach, Virology 168:138-146,
      1989). Previous work in our laboratory has identified point mutations in the CCMV
      coat protein which result in virions with altered swelling characteristics (J.
      Fox, F. G. Albert, J. Speir, and M. J. Young, Virology 227:229-233, 1997; J. M.
      Fox, X. Zhao, J. A. Speir, and M. J. Young, Virology 222:115-122, 1996). The wild
      type and mutant CCMV virions were used to correlate virion swelling with the
      ability of virion RNA to be translated in a cell-free wheat germ extract. Mutant
      virions unable to swell (cpK42R) are as infectious as wild-type virions in vivo,
      and the levels of translated encapsidated virion RNA are similar to those of wild
      type virions in vitro. Mutant virions capable of swelling but not of
      disassembling in vitro (cpR26C) are noninfectious and have severely reduced
      levels of translation of the encapsidated virion RNA in vitro. These studies
      suggest that virion swelling is not required for the cotranslational disassembly
      of CCMV. Additionally, the results indicate that there is a pH-dependent
      structural transition in the virion, other than swelling, that results in the
      RNA's being exposed for translation in vitro. An alternative model suggesting
      that cotranslational disassembly of CCMV involves presentation of the virion RNA
      through the virion fivefold axis is proposed.

PMID- 9151816
TI  - Divergent patterns of progression to AIDS after infection from the same source:
      human immunodeficiency virus type 1 evolution and antiviral responses.
AB  - The rate of progression to AIDS in human immunodeficiency virus type 1 (HIV-1)
      infected individuals is determined by a complex series of interactions between
      the host and virus. Here we evaluate virologic properties and host responses in
      two men near-simultaneously infected with HIV-1 from the same sexual partner--one
      individual progressed to AIDS in less than 2 years, and the other remains
      asymptomatic 3 years postinfection. Distinct neutralizing antibody and cellular
      immune responses were evident, with the slower progressor exhibiting generally
      stronger and broader responses, except for cytotoxic T-lymphocyte responses early
      in infection. Virtually identical, homogeneous virus populations were found in
      both patients in the first sample obtained; however, a second unrelated HIV-1
      virus population was also found in the fast progressor. Whether the second
      population emanated from an additional source of infection or the two were
      transmitted from the original source could not be determined. The virus
      population in the slower progressor turned over and diversified rapidly, whereas
      both virus populations in the rapid progressor evolved at a much slower rate. In
      addition, the character of mutational changes underlying these diversities
      appeared to be distinct, with a bias for diversifying selection developing in the
      slower progressor and a reciprocal bias towards purifying selection maintained in
      both populations in the fast progressor. Thus, the rapid evolution that is a
      hallmark of HIV replication may be a reflection of strong host resistance against
      emerging virus variants and a longer period of asymptomatic infection.
      Furthermore, rapid progression was not linked to a collapse of any appreciable
      immune response following attainment of some threshold of antigenic diversity but
      rather to a failure to drive this diversification and a condition of relatively
      unimpeded expansion of variants with optimized replicative capacity within the
      host.

PMID- 9151818
TI  - The adeno-associated virus type 2 p40 promoter requires a proximal Sp1
      interaction and a p19 CArG-like element to facilitate Rep transactivation.
AB  - We have identified the sequence elements that are required for adeno-associated
      virus type 2 p40 promoter activity. Mutation of specific promoter elements showed
      that two Sp1 sites at approximately -50 (Sp1-50) and -70 (GGT-70) bp upstream of
      the start of the p40 messages were necessary for maximal promoter activity. As
      expected, the TATA site at -30 was also essential. In vitro DNA binding
      experiments confirmed that the Sp1-50 and GGT-70 sites were bound by Sp1 or Sp1
      like proteins. Two other transcription elements, the ATF-80 and AP1-40 sites, may
      play a role in p40 activity. Mutation of these elements resulted in a modest
      decrease in p40 transcription, but DNA binding experiments did not clearly
      demonstrate binding of transcription factors to these sites. In contrast, a major
      late transcription factor site at -110 was shown to bind the transcription
      factor, but mutation of this site had no effect on p40 activity. In a previous
      report, we have shown that transactivation of the p40 promoter by the viral Rep
      proteins required an upstream Rep binding element (in the terminal repeat or the
      p5 promoter), an unidentified p19 promoter element, and a p40 promoter element
      (D. J. Pereira and N. Muzyczka, J. Virol. 71:1747-1756, 1997). Here we
      demonstrate that the CArG-140 element in the p19 promoter and the Sp1-50 element
      in the p40 promoter are the specific p19 and p40 elements required for Rep
      induction of p40. As in the case of the p19 promoter, Sp1 facilitates interaction
      of Rep with the p40 promoter by interaction of the two proteins. Furthermore,
      electron microscopy experiments demonstrated that when Rep is bound to an
      upstream Rep binding element, it can interact with a proximal Sp1 site by protein
      contacts and create a loop in the intervening DNA. This finding suggests a common
      mechanism whereby the Rep binding element in the TR or the p5 promoter induces
      p19 and p40 activity by interaction with their respective Sp1 sites.

PMID- 9151819
TI  - Human papillomavirus type 16 E6 protein transcriptionally modulates fibronectin
      gene expression by induction of protein complexes binding to the cyclic AMP
      response element.
AB  - Although human papillomavirus type 16 (HPV16) E6 protein has a transcription
      modulatory activity for a wide variety of viral promoters, a cellular target for
      this activity of E6 has not yet been identified. In this study, using
      differential hybridization, we identified a mouse fibronectin (FN) gene as a
      putative cellular target whose expression is up-regulated by E6. Chloramphenicol
      acetyltransferase (CAT) assays with mouse and rat FN promoter-CAT fusion
      constructs indicated that HPV16 E6 transactivates the FN promoters in a p53
      independent manner. Deletion and site-specific mutation analyses revealed that
      transactivation by HPV16 E6 depends upon a cyclic AMP response element (CRE)
      located at -160 relative to the start site of transcription. Gel retardation
      assays demonstrated that nuclear extracts from the HPV16 E6-expressing cells,
      compared to those from parental 10T1/2 cells, have increased binding activity to
      the CRE. Antibodies against c-Jun and ATF-2 disrupted this binding activity.
      These data indicate that HPV16 E6 transcriptionally modulates FN gene expression
      via the CRE by inducing the binding of the protein complexes, probably including
      c-Jun and ATF-2, to the CRE.

PMID- 9151820
TI  - Antibodies with specificity to native gp120 and neutralization activity against
      primary human immunodeficiency virus type 1 isolates elicited by immunization
      with oligomeric gp160.
AB  - Current human immunodeficiency virus type 1 (HIV-1) envelope vaccine candidates
      elicit high antibody binding titers with neutralizing activity against T-cell
      line-adapted but not primary HIV-1 isolates. Serum antibodies from these human
      vaccine recipients were also found to be preferentially directed to linear
      epitopes within gp120 that are poorly exposed on native gp120. Systemic
      immunization of rabbits with an affinity-purified oligomeric gp160 protein
      formulated with either Alhydrogel or monophosphoryl lipid A-containing adjuvants
      resulted in the induction of high-titered serum antibodies that preferentially
      bound epitopes exposed on native forms of gp120 and gp160, recognized a
      restricted number of linear epitopes, efficiently bound heterologous strains of
      monomeric gp120 and cell surface-expressed oligomeric gp120/gp41, and neutralized
      several strains of T-cell line-adapted HIV-1. Additionally, those immune sera
      with the highest oligomeric gp160 antibody binding titers had neutralizing
      activity against some primary HIV-1 isolates, using phytohemagglutinin-stimulated
      peripheral blood mononuclear cell targets. Induction of an antibody response
      preferentially reactive with natively folded gp120/gp160 was dependent on the
      tertiary structure of the HIV-1 envelope immunogen as well as its adjuvant
      formulation, route of administration, and number of immunizations administered.
      These studies demonstrate the capacity of a soluble HIV-1 envelope glycoprotein
      vaccine to elicit an antibody response capable of neutralizing primary HIV-1
      isolates.

PMID- 9151822
TI  - Retention of viral infectivity after extensive mutation of the highly conserved
      immunodominant domain of the feline immunodeficiency virus envelope.
AB  - In lentiviruses, including human immunodeficiency virus and feline
      immunodeficiency virus (FIV), the principal immunodominant domain (PID) of the
      transmembrane glycoprotein elicits a strong humoral response in infected hosts.
      The PID is marked by the presence of two cysteines that delimit a sequence,
      composed of five to seven amino acids in different lentiviruses, which is highly
      conserved among isolates of the same lentiviral species. While the conservation
      of the sequence suggests the presence of functional constraints, the conservation
      of the immunodominance among divergent lentiviruses raises the hypothesis of a
      selective advantage for the infecting virus conferred by the host humoral
      response against this domain. We and others have previously shown that an
      appropriate structure of the PID is required for the production of a functional
      envelope. In the present work, we analyzed virological functions and immune
      reactivity of the envelope after random mutagenesis of the PID of FIV. We
      obtained nine mutant envelopes which were correctly processed and retained
      fusogenic ability. Mutation of the two C-terminal residues of the PID sequence
      between the cysteines in a molecular clone of FIV abolished infectivity. In
      contrast, three molecular clones containing extensive mutations in the four N
      terminal amino acids were infectious. However, the mutations affected PID
      reactivity with sera from infected cats. Our results suggest that functional
      constraints, although existent, are not sufficient to account for PID sequence
      conservation. Such conservation may also result from positive selection by anti
      PID antibodies which enhance infection.

PMID- 9151821
TI  - Conservation and host specificity of Vpr-mediated cell cycle arrest suggest a
      fundamental role in primate lentivirus evolution and biology.
AB  - The human immunodeficiency virus type 1 (HIV-1) Vpr protein prevents infected
      cells from passing through mitosis by arresting them in the G2 phase of the cell
      cycle. Vpr is conserved among all primate lentiviruses, suggesting an important
      role in the virus life cycle. Moreover, in this study we show that the ability to
      cause cell cycle arrest is also conserved in Vpr proteins from a wide variety of
      both tissue culture-passaged and uncultured human (HIV-1 and HIV-2), sooty
      mangabey (simian immunodeficiency virus SIV(SM)), African green monkey
      (SIV(AGM)), and Sykes' monkey (SIV(SYK)) isolates. However, this property is cell
      type specific and appears to depend on the particular primate species from which
      the cells are derived. SIV(AGM) and SIV(SYK) Vpr proteins are capable of
      arresting African green monkey cells but are completely inactive in human cells.
      By contrast, HIV-1, HIV-2, and SIV(SM) Vpr proteins function in both simian and
      human cell types, although SIV(SM) Vpr functions more efficiently in simian cells
      than it does in human cells. Neither differential protein stability nor
      subcellular localization explains the species-specific activities of these
      proteins. These results thus suggest that Vpr exerts its G2 arrest function by
      interacting with cellular factors that have evolved differently among the various
      primate species.

PMID- 9151823
TI  - A pulmonary influenza virus infection in SCID mice can be cured by treatment with
      hemagglutinin-specific antibodies that display very low virus-neutralizing
      activity in vitro.
AB  - We have previously shown that a pulmonary influenza virus infection in SCID mice
      can be cured by treatment with monoclonal antibodies (MAbs) specific for the
      viral transmembrane protein hemagglutinin (HA) but not for matrix 2. Since both
      types of MAbs react with infected cells but only the former neutralizes the
      virus, it appeared that passive MAbs cured by neutralization of progeny virus
      rather than reaction with infected host cells. To prove this, we selected a set
      of four HA-specific MAbs, all of the immunoglobulin G2a isotype, which reacted
      well with native HA expressed on infected cells yet differed greatly (>10,000
      fold) in virus neutralization (VN) activity in vitro, apparently because of
      differences in antibody avidity and accessibility of the respective determinants
      on the HA of mature virions. Since the VN activities of these MAbs in vitro were
      differentially enhanced by serum components, we determined their prophylactic
      activities in vivo and used them as measures of their actual VN activities in
      vivo. The comparison of therapeutic and prophylactic activities indicated that
      these MAbs cured the infection to a greater extent by VN activity (which was
      greatly enhanced in vivo) and to a lesser extent by reaction with infected host
      cells. Neither complement- nor NK cell-dependent mechanisms were involved in the
      MAb-mediated virus clearance.

PMID- 9151824
TI  - The purified myxoma virus gamma interferon receptor homolog M-T7 interacts with
      the heparin-binding domains of chemokines.
AB  - The myxoma virus T7 protein M-T7 is a functional soluble gamma interferon
      receptor homolog that has previously been shown to bind gamma interferon and
      inhibit its antiviral activities in a species-specific manner, but gene knockout
      analysis has suggested a further role for M-T7 in blocking leukocyte influx into
      infected lesions. We purified M-T7 to apparent homogeneity and showed that M-T7
      is an N-linked glycoprotein that appears to be a stable homotrimer with a
      molecular mass of approximately 113 kDa in solution. M-T7, in addition to forming
      inhibitory complexes with rabbit gamma interferon, was also shown to bind to
      human interleukin-8, a prototypic member of the chemokine superfamily. Moreover,
      M-T7 was able to interact promiscuously with all members of the CXC, CC, and C
      chemokine subfamilies tested. Binding of human RANTES to M-T7 can be competed by
      rabbit gamma interferon and also by cold RANTES competitor with a 50% inhibitory
      concentration of 900 nM. Although M-T7 retains binding to a number of interleukin
      8 N-terminal (ELR) deletion mutants, binding to mutants containing deletions in
      the C-terminal heparin-binding domain of interleukin-8 is abrogated. Furthermore,
      heparin effectively competes the interaction of M-T7 with the chemokine RANTES
      but not with rabbit gamma interferon. We propose that this novel M-T7 interaction
      with members of the chemokine superfamily may be facilitated through the
      conserved heparin-binding domains found in a wide spectrum of chemokines and that
      M-T7 may function by modulating chemokine-glycosaminoglycan interactions in virus
      infected tissues.

PMID- 9151825
TI  - Upregulation of signalase processing and induction of prM-E secretion by the
      flavivirus NS2B-NS3 protease: roles of protease components.
AB  - Recently, we have shown that the ability of the flavivirus NS2B-NS3 protease
      complex to promote efficient signalase processing of the C-prM precursor, as well
      as secretion of prM and E, does not appear to depend strictly on cleavage of the
      precursor at its Lys-Arg-Gly dibasic site by the protease. We suggested that the
      association of the protease with the precursor via NS2B may be sufficient by
      itself for the above effects. To study the proposed association in more detail,
      we have developed an assay in which processing at the C-prM dibasic cleavage site
      is abolished by Lys-->Gly conversion. We constructed deletion mutants and
      chimeras of the West Nile (WN) flavivirus NS2B protein and expressed them in the
      context of [5'-C-->NS3(243)] containing either wild-type C-prM or its cleavage
      site mutant. All NS2B variants were able to form active protease complexes.
      Deletion of the carboxy-terminal cluster of hydrophobic amino acids in NS2B had
      no apparent effect on the formation of prM and prM-E secretion for the cassettes
      containing either wild-type or mutated C-prM precursor. Deletion of the amino
      terminal hydrophobic cluster in NS2B did not affect prM-E secretion for the
      cassettes with wild-type C-prM but abrogated prM-E secretion for the cassettes
      with the mutated dibasic cleavage site in C-prM. Similarly, the NS2B-NS3(178)
      protease of Japanese encephalitis (JE) virus, when substituted for the WN virus
      NS2B-NS3(243) protease, was able to promote prM-E secretion for the cassette with
      the wild-type C-prM precursor but not with the mutated one. Replacement of the
      deleted amino-terminal hydrophobic cluster in the WN virus NS2B protein with an
      analogous JE virus sequence restored the ability of the protease to promote prM-E
      secretion. On the basis of these observations, roles of individual protease
      components in upregulation of C-prM signalase processing are discussed.

PMID- 9151826
TI  - The Nef protein of human immunodeficiency virus type 1 enhances serine
      phosphorylation of the viral matrix.
AB  - The human immunodeficiency virus type 1 matrix (MA) protein is phosphorylated
      during virion maturation on its C-terminal tyrosine and on several serine
      residues. Whereas MA tyrosine phosphorylation facilitates viral nuclear import,
      the significance of MA serine phosphorylation remains unclear. Here, we report
      that MA serine but not tyrosine phosphorylation is strongly enhanced by Nef.
      Mutations that abrogated the membrane association of Nef and its ability to bind
      a cellular serine/threonine kinase greatly diminished the extent of virion MA
      serine phosphorylation. Correspondingly, a protein kinase coimmunoprecipitated
      with Nef could phosphorylate MA on serine in vitro, producing a phosphopeptide
      pattern reminiscent of that of virion MA. Recombinant p21-activated kinase
      hPAK65, a recently proposed relative of the Nef-associated kinase, achieved a
      comparable result. Taken together, these data suggest that MA is a target of the
      Nef-associated serine kinase.

PMID- 9151828
TI  - Mutant adenovirus type 9 E4 ORF1 genes define three protein regions required for
      transformation of CREF cells.
AB  - Human adenovirus type 9 (Ad9) elicits exclusively estrogen-dependent mammary
      tumors in rats, and an essential oncogenic determinant for this virus is Ad9 E4
      open reading frame 1 (9ORF1), which encodes a 125-residue cytoplasmic protein
      with cellular growth-transforming activity in vitro. In this study, we engineered
      48 different mutant 9ORF1 genes in an attempt to identify regions of this viral
      protein essential for transformation of the established rat embryo fibroblast
      cell line CREF. In initial assays with CREF cells, 17 of the 48 mutant 9ORF1
      genes proved to be severely defective for generating transformed foci but only 7
      of these defective genes expressed detectable amounts of protein. To further
      examine the defects of the seven mutant proteins, we selected individual cell
      pools of stable CREF transformants for the wild-type and mutant 9ORF1 genes.
      Compared to cell pools expressing the wild-type 9ORF1 protein, most cell pools
      expressing mutant proteins displayed decreased growth in soft agar, and all
      generated significantly smaller tumors in syngeneic animals. The altered amino
      acid residues of the seven mutant 9ORF1 polypeptides clustered within three
      separate regions referred to as region I (residues 34 to 41), region II (residues
      89 to 91), and C-terminal region III (residues 122 to 125). By using indirect
      immunofluorescence, we also assessed whether the mutant proteins localized
      properly to the cytoplasm of cells. The region I and region II mutants displayed
      approximately wild-type subcellular localizations, whereas most region III
      mutants aberrantly accumulated within the nucleus of cells. In summary, we have
      identified three 9ORF1 protein regions necessary for cellular transformation and
      have demonstrated that C-terminal region III sequences significantly influence
      the proper localization of the 9ORF1 polypeptide in cells.

PMID- 9151827
TI  - Effect of mutations in the nucleocapsid protein (NCp7) upon Pr160(gag-pol) and
      tRNA(Lys) incorporation into human immunodeficiency virus type 1.
AB  - COS-7 cells were transfected with DNAs containing mutations in the NCp7 sequences
      of human immunodeficiency virus. Selective incorporation into the virus of
      tRNA(Lys) was measured by two-dimensional polyacrylamide gel electrophoresis, and
      Pr160(gag-pol) incorporation into the virus was detected in Western blots of
      viral protein. Mutations tested included cysteine and histidine mutations in
      either of the Cys-His boxes, as well as mutations in the N- and C-terminal
      flanking regions and in the linker region between the two Cys-His boxes. Of 10
      mutations tested, only 2 inhibited tRNA(Lys) incorporation: a P31L mutation in
      the linker region and a deletion which removed both Cys-His boxes and the linker
      region (deltaK14-T50). The P31L mutation prevents the incorporation of Pr160(gag
      pol) into the virus. Cotransfection of COS cells with both P31L DNA and a plasmid
      coding only for unprocessed Pr160(gag-pol) resulted in the viral incorporation of
      Pr160(gag-pol) and the rescue of selective packaging of tRNA(Lys) into the
      virion. In the deltaK14-T50 mutant, Pr160(gag-pol) is incorporated into the
      virus. Selective tRNA(Lys) packaging is not rescued by cotransfection with a
      plasmid coding for Pr160(gag-pol) but is rescued by cotransfection with DNA
      coding for wild-type Pr55(gag). Since Pr55(gag) does not by itself selectively
      package tRNA(Lys), the deltaK14-T50 mutation may be affecting tRNA(Lys) binding
      to a cytoplasmic Pr55(gag)/Pr160(gag-pol) complex.

PMID- 9151829
TI  - Analysis of LaCrosse virus S mRNA 5' termini in infected mosquito cells and Aedes
      triseriatus mosquitoes.
AB  - Nucleotide sequences were determined for the 5' termini of La Crosse virus (LAC)
      S segment mRNA from persistently infected mosquito cell cultures (C6/36 from
      Aedes albopictus) and embryos (Aedes triseriatus). LAC primes transcription of
      its mRNA with "scavenged" 5' caps and adjacent oligonucleotides from host mRNAs,
      and these non-virus-encoded 5'-terminal extensions are heterogeneous in infected
      mammalian cells. The nature of mosquito host-derived primers has not been
      previously investigated. During early C6/36 cell infection, LAC mRNA 5'-terminal
      sequences were heterogeneous, but variability decreased as infection persisted.
      One predominant sequence, 5' CCACTCGCCACT (sequence 1), was observed throughout
      C6/36 cell infection but was more prevalent after 15 days postinfection. This LAC
      mRNA 5'-terminal sequence comprised 81% of the scavenged host oligonucleotides
      from vertically infected A. triseriatus eggs during embryogenesis. As these
      embryos progressed in the dormant overwintering stage (diapause), the predominant
      scavenged sequence became 5' AGGAAAAGATGGT (sequence 2), and sequence 1 became
      less prevalent. As the eggs emerged from diapause, the LAC mRNA 5' termini were
      more variable; 33% had sequence 1, and the remainder were heterogeneous. In post
      diapausing eggs, 100% of viral mRNAs had sequence 1 at their 5' termini.
      Molecular analyses thus revealed continuous but selective LAC cap scavenging
      during persistent C6/36 cell infection and during embryogenesis and diapause in
      A. triseriatus eggs. The variety of host-derived sequences was limited in both
      biosynthetically active (embryonating) and dormant (diapausing) eggs.

PMID- 9151831
TI  - Characterization of human immunodeficiency virus type 1 matrix revertants:
      effects on virus assembly, Gag processing, and Env incorporation into virions.
AB  - The matrix protein of human immunodeficiency virus type 1 (HIV-1) has been
      postulated to serve a variety of functions in the virus life cycle. Previously,
      we introduced a large number of mutations into the HIV-1 matrix and determined
      the effects on virus replication. These studies identified domains involved in
      virus assembly and release and envelope glycoprotein incorporation into virions.
      Here we describe the identification and characterization of viral revertants
      containing second-site changes in the matrix which compensate for the effects of
      four of the original mutations on matrix function. Specifically, mutations at
      matrix residues 4 and 6 severely impaired virus assembly and release;
      substitutions at residues 4 and 6 reversed the phenotype of the amino acid 4
      change while second-site mutations at matrix positions 10, 69, and 97 partially
      or fully reversed the phenotype of the amino acid 6 substitution. A mutation at
      matrix residue 62 reversed the effect of a position 34 change which blocks
      envelope glycoprotein incorporation into virions, and substitutions at residues
      27 and 51 reversed the phenotype of a position 86 mutation which redirects virus
      assembly to the cytoplasm. In addition to determining the effects of the
      compensatory changes in the context of the original mutations, we also introduced
      and analyzed the second-site changes alone in the context of the wild-type
      molecular clone. The data presented here define potential intermolecular and
      intramolecular interactions which occur in the matrix during the virus life cycle
      and have implications for our understanding of the relationship between matrix
      structure and function.

PMID- 9151830
TI  - Human cytomegalovirus tegument protein pp71 (ppUL82) enhances the infectivity of
      viral DNA and accelerates the infectious cycle.
AB  - Three tegument proteins of human cytomegalovirus (HCMV), ppUL82 (pp71), pUL69,
      and ppUL83 (pp65), were examined for the ability to stimulate the production of
      infectious virus from human diploid fibroblasts transfected with viral DNA.
      Although viral DNA alone had a low intrinsic infectivity of 3 to 8 plaques/microg
      of viral DNA, cotransfection of a plasmid expressing pp71 increased the
      infectivity of HCMV DNA 30- to 80-fold. The increase in infectivity produced by
      pp71 was reflected in an increased number of nuclei observed to express high
      levels of the major immediate-early proteins IE1 and IE2. Cotransfection of viral
      DNA with plasmids directing expression of IE1 and IE2 also resulted in extensive
      IE1 and IE2 expression in the transfected cells; however, the infectivity of
      viral DNA was only marginally increased. pp71 also facilitated late gene
      expression, virus transmission to adjacent cells, and plaque formation. In
      contrast, expression of pUL69 reduced the pp71- and IE1/IE2-mediated enhancement
      of HCMV DNA infectivity and also failed to produce any increase in the number of
      cells expressing IE1 and IE2 over that seen with viral DNA alone. Expression of
      pp65 did not alter the infectivity of HCMV DNA, nor did it modify the effects of
      pp71 or pUL69. These results imply that pp71 plays a critical role in the
      initiation of infection apart from its function as a transactivator of IE1 and
      IE2.

PMID- 9151832
TI  - CD4-independent infection by human immunodeficiency virus type 2 strain ROD/B:
      the role of the N-terminal domain of CXCR-4 in fusion and entry.
AB  - The human immunodeficiency virus type 2 (HIV-2) strain ROD/B can efficiently use
      the 7tm chemokine receptor CXCR-4 as a primary receptor to enter CD4-negative
      cells. We have stably expressed CXCR-4 on mink lung Mv-1-lu and feline kidney CCC
      cells (normally restrictive to HIV entry) and have shown efficient fusion, entry,
      and replication of ROD/B. Mutation of the two N-linked glycosylation sites on
      CXCR-4 (N11-->I, and N176-->Q) or pretreatment of CCC or Mv-1-lu cells expressing
      wild-type CXCR-4 with the glycosylation inhibitor tunicamycin increased fusion
      and entry by ROD/B. Deletion of portions of the N terminus of CXCR-4 resulted in
      a 3- to 10-fold decrease in cell-free infection by ROD/B and complete inhibition
      of cell-cell fusion by both ROD/B and another HIV-2 strain, CBL23. These data
      suggest that the N-terminal domain of CXCR-4 is involved in but is not essential
      for the efficient fusion of ROD/B with CD4-negative cells. Deletion of the C
      terminal (intracellular) domain of CXCR-4 did not significantly affect entry by
      ROD/B, indicating that intracellular signalling through this domain does not play
      a significant role in entry by HIV-2.

PMID- 9151833
TI  - In vitro assembly of virus-like particles with Rous sarcoma virus Gag deletion
      mutants: identification of the p10 domain as a morphological determinant in the
      formation of spherical particles.
AB  - Retroviruses are unusual in that expression of a single protein, Gag, leads to
      budding of virus-like particles into the extracellular space. We have developed
      conditions under which virus-like particles are formed spontaneously in vitro
      from fragments of Rous sarcoma virus (RSV) Gag protein purified after expression
      in Escherichia coli. The CA-NC fragment of Gag was shown previously to assemble
      into hollow cylinders (S. Campbell and V. M. Vogt, J. Virol. 69:6487-6497, 1995).
      We have now extended these studies to larger Gag proteins. In every case
      examined, assembly into regular structures required RNA. A nearly full-length Gag
      missing only the C-terminal PR domain, as well as similar proteins missing in
      addition the N-terminal half of MA, the C-terminal half of MA, the entire MA
      sequence, or the entire p2 sequence, all assembled into spherical particles
      resembling RSV in size. By contrast, proteins missing p10 assembled into
      cylindrical particles like those formed by CA-NC alone. Thin section electron
      microscopy showed that each of these Gag proteins formed in the expressing E.
      coli cells particles similar in shape to those seen in vitro. We conclude from
      these results that neither the sequences required for membrane binding in vivo,
      near the N terminus of Gag, nor the sequences required for a late step in
      budding, in the p2 portion of Gag, are essential for formation of virus-like
      particles in this system. Furthermore, we postulate the existence of a shape
      determining sequence in p10, which provides or facilitates interactions required
      for the growing particle to be constrained to a spherical shape.

PMID- 9151834
TI  - Differential susceptibility of naive and memory CD4+ T cells to the cytopathic
      effects of infection with human immunodeficiency virus type 1 strain LAI.
AB  - CD4+ T lymphocytes of individuals infected with human immunodeficiency virus type
      1 (HIV-1) exhibit a qualitative defect in their ability to mount memory responses
      to previously encountered antigens although their responses to mitogens remain
      normal. T cells responsible for memory responses can be distinguished from naive
      T cells based on differential expression of isoforms of the tyrosine phosphatase
      CD45. It has been suggested that memory CD4+ T cells from infected individuals
      have a greater virus burden than naive CD4+ T cells and that this accounts for
      the loss of recall responses in infected individuals. However, it has been
      unclear whether naive and memory T cells are equally susceptible to infection and
      to the cytopathic effects of the virus. We therefore infected highly purified
      resting naive and memory CD4+ T cells from HIV-1-seronegative individuals with
      HIV-1(LAI). Infected cells were then stimulated with phytohemagglutinin to render
      them permissive for viral replication. Cell viability and growth rate were
      monitored for 8 to 10 days as indicators of cytopathic effects induced by HIV
      1(LAI). Our results indicated that naive and memory CD4+ T cells display marked
      differences in susceptibility to the cytopathic effects induced by HIV-1(LAI),
      infection. The cytopathic effects induced by HIV-1(LAI) were much more severe in
      memory CD4+ T cells than in naive CD4+ T cells. Differential cytopathic effects
      in naive and memory T cells were not due to differences in virus entry into and
      replication in these cell populations. Rather, memory cells were more susceptible
      to cytopathic effects. Pronounced cytopathic effects in memory cells were clearly
      detectable at 7 day postinfection. Cell death occurred at the single-cell level
      and was not accompanied by syncytium formation. The growth rate of infected
      memory CD4+ T cells was also severely compromised compared to that of naive CD4+
      T cells, whereas the growth rates of both uninfected naive and memory CD4+ T
      cells were approximately the same. At least a portion of the dying cells
      exhibited biochemical changes characteristic of apoptosis. These results suggest
      that the selective functional defects present in the memory CD4+ T-cell subset of
      HIV-1-infected individuals may in part be the result of the greater
      susceptibility of memory T cells to cytopathic effects induced by HIV-1.

PMID- 9151835
TI  - Human T-cell leukemia virus type 1 Tax protein transforms rat fibroblasts via two
      distinct pathways.
AB  - The human T-cell leukemia virus type 1 (HTLV-1) Tax protein activates the
      transcription of several cellular genes. This function is thought to play a
      critical role in the Tax-dependent transformation step in HTLV-1 leukemogenesis.
      Tax activates transcription via three enhancers: the cyclic AMP response element
      (CRE)-like sequence, the kappaB element, and the CArG box. Their involvement in
      the transformation of rat fibroblasts by Tax was examined by colony formation of
      Rat-1 cells in soft agar and Ras cooperative focus formation of rat embryo
      fibroblasts (REF). Among Tax mutants, those retaining activity for the CArG box
      transformed REF like wild-type Tax, while those inactive for the CArG box did
      not. Thus, the activation of the CArG box pathway is essential for the
      transformation of REF by Tax. In contrast, activation of the kappaB element
      correlated with the transformation of Rat-1 by Tax. These results show that Tax
      transforms rat fibroblasts via two distinct pathways.

PMID- 9151836
TI  - Putative alpha-helical structures in the human immunodeficiency virus type 1 Vpu
      protein and CD4 are involved in binding and degradation of the CD4 molecule.
AB  - The human immunodeficiency virus type 1 (HIV-1) vpu gene encodes a 16-kDa class I
      integral membrane phosphoprotein with an N-terminal membrane-spanning region and
      a C-terminal cytoplasmic domain. In the cytoplasmic domain, two amphipathic alpha
      helices joined by a flexible turn containing two phosphoacceptor sites have been
      predicted. Previous studies have shown that Vpu downregulates CD4 molecules by
      inducing their specific degradation in the endoplasmic reticulum. Phosphorylation
      of serine residues 52 and 56, present within the cytoplasmic domain of the Vpu
      protein, has been shown to be essential to this Vpu function. However, the
      contribution of these two phosphoacceptor sites in the mechanism of CD4
      degradation remains undefined. Interestingly, a specific interaction between Vpu
      and CD4 was recently demonstrated in coimmunoprecipitation experiments. Binding
      of Vpu was shown to be necessary but not sufficient to mediate CD4 degradation,
      indicating that interaction between Vpu and CD4 represents an early step critical
      in triggering a process leading to CD4 degradation. To delineate the sequence(s)
      and/or structural determinant(s) involved in this Vpu-CD4 interaction and in the
      Vpu-mediated CD4 degradation, we performed a mutational analysis of the
      cytoplasmic domain of CD4 and Vpu. Coimmunoprecipitation experiments reveal that
      disruption of the putative alpha-helical structure in the membrane-proximal
      cytoplasmic domain of CD4 affects the binding to Vpu, suggesting that this
      structure may act as an interface for the CD4-Vpu interaction that mediates CD4
      degradation. Vpu proteins containing mutations in either or both of the
      phosphoacceptor sites (Ser52 or/and Ser56) were inactive in regard to CD4
      degradation yet retained the capacity to interact with the cytoplasmic domain of
      CD4. In an attempt to define the minimal region responsible for this interaction,
      we tested a panel of mutations which were designed to affect the integrity of the
      putative alpha-helices present in the cytoplasmic domain of Vpu. Our results
      indicate that although both C-terminal alpha-helices are required for degradation
      of CD4, only alpha-helix I, located in the membrane-proximal cytoplasmic region
      of Vpu, is involved in the interaction between Vpu and CD4. Taken together, these
      results demonstrate that alpha-helical structures in the HIV-1 Vpu and CD4
      proteins are involved in binding and degradation of CD4 molecules.

PMID- 9151838
TI  - Incorporation of Pr160(gag-pol) into virus particles requires the presence of
      both the major homology region and adjacent C-terminal capsid sequences within
      the Gag-Pol polyprotein.
AB  - The determinants critical for the incorporation of Pr160(gag-pol) into human
      immunodeficiency virus type 1 (HIV-1) particles were examined by cotransfecting
      cells with (i) a plasmid expressing wild-type Gag protein and (ii) a series of
      chimeric Gag-Pol expression plasmids in which individual murine leukemia virus
      (MLV) Gag regions and subdomains precisely replaced their HIV-1 counterparts. The
      presence of the MLV MA and NC Gag regions in the chimeric Gag-Pol precursor had
      no detectable effect on the incorporation of Gag-Pol into progeny virions. In
      contrast, the entire HIV-1 CA region was required to achieve wild-type levels of
      Gag-Pol assembly into particles; both the CA major homology region and the
      adjacent C-terminal CA sequences play dominant roles in this process yet, when
      assayed in the context of a chimeric Gag-Pol polyprotein, restored the defect
      affecting Gag-Pol incorporation to approximately half of the wild-type level.

PMID- 9151837
TI  - The Rep78 gene product of adeno-associated virus (AAV) self-associates to form a
      hexameric complex in the presence of AAV ori sequences.
AB  - The Rep78 and Rep68 proteins of adeno-associated virus (AAV) are replication
      initiator proteins that bind the viral replicative-form origin of replication,
      nick the origin in a site- and strand-specific fashion, and mediate vectorial
      unwinding of the DNA duplex via an ATP-dependent helicase activity, thus
      initiating a strand displacement mechanism of viral DNA replication. Genetic and
      biochemical studies have identified Rep mutants that demonstrate a trans-dominant
      negative phenotype in vitro and in vivo, suggesting the possibility that
      multimerization of Rep is essential for certain replicative functions. In this
      study, we have investigated the ability of the largest of the Rep proteins,
      Rep78, to self-associate in vitro and in vivo. Self-association of Rep78 in vivo
      was demonstrated through the use of a mammalian two-hybrid system. Rep-Rep
      protein interaction was confirmed in vitro through coimmunoprecipitation
      experiments with a bacterially expressed maltose-binding protein-Rep78 fusion
      protein in combination with [35S]methionine-labeled Rep78 synthesized in a
      coupled in vitro transcription-translation system. Mapping studies with N- and C
      terminal truncation mutant forms of Rep indicate that amino acid sequences
      required for maximal self-association occur between residues 164 and 484. Site
      directed mutagenesis identified two essential motifs within this 321-amino-acid
      region: (i) a putative alpha-helix bearing a 3,4-hydrophobic heptad repeat
      reminiscent of those found in coiled-coil domains and (ii) a previously
      recognized nucleoside triphosphate-binding motif. Deletion of either of these
      regions from the full-length polypeptide resulted in severe impairment of Rep-Rep
      interaction. In addition, gel filtration chromatography and protein cross-linking
      experiments indicated that Rep78 forms a hexameric complex in the presence of AAV
      ori sequences.

PMID- 9151839
TI  - Broad spectrum of in vivo fitness of human immunodeficiency virus type 1
      subpopulations differing at reverse transcriptase codons 41 and 215.
AB  - Viral populations in a human immunodeficiency virus type 1 (HIV-1)-infected
      individual behave as a quasispecies with a rated distribution of fitness
      variants. Fitness distributions in naturally occurring viral populations have
      been difficult to study due to the lack of markers for individual virus clones
      and complicating inter- and intrahost factors like the presence of multiple cell
      types with distinct tropisms, differences in route of transmission, and
      intervening immunity. Here, we quantitated the relative fitness in vivo of three
      subpopulations of HIV-1 marked by mutations at codons 41 and 215 of reverse
      transcriptase (RT) directly related to zidovudine resistance in an untreated
      individual who was infected by a zidovudine-resistant strain transmitted from a
      donor on therapy. The transmission event did not have a substantial impact on the
      distribution of mutants within the dominant virus population replicating to high
      levels in the recipient. The evolution of the RT gene was monitored for 20
      months. All 102 clones obtained from the donor and the recipient at the different
      time points contained the M41L mutation, which is associated with a fourfold
      reduction in zidovudine sensitivity. The leucine at position 41 was stable,
      although it was encoded by TTG and CTG triplets that fluctuated in abundance
      partially due to founder effects of clones with nonsilent mutations at codon 215.
      Of the three subpopulations in the patient, distinguished by a tyrosine (TAC),
      aspartic acid (GAC), or serine (TCC) at the 215 position of RT, the relative
      fitness of the GAC variant was calculated to be 10 to 25% higher than the initial
      TAC variant, and the relative fitness of the TCC variant was 1% higher than that
      of the GAC variant. Similar to other RNA viruses, lentivirus populations like HIV
      1 in patients with a high virus load apparently consist of a broader spectrum of
      fitness variants than the 1 to 2% fitness difference sufficient for significant
      replicative advantage.

PMID- 9151840
TI  - cis-Acting inhibitory elements within the pol-env region of human T-cell leukemia
      virus type 1 possibly involved in viral persistence.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) remains latent throughout the life of
      the carrier, with cells containing the provirus and viral gene expression
      efficiently down-regulated. On a molecular level, exactly how viruses are down
      regulated in vivo remains unresolved. We described here the possibility that down
      regulation results from the presence of inhibitory elements within the gag-env
      region of the provirus in fresh peripheral blood mononuclear cells from carriers.
      In vitro experiments then revealed that potent cis-acting inhibitory elements
      (CIEs) are indeed contained in two discrete fragments from the pol region and
      weaker ones in the env region. The effect of CIEs is relieved by the HTLV-1
      posttranscriptional regulator Rex through binding to the Rex-responsive element
      (RxRE), suggesting that Rex might interfere with pre-mRNA degradation and/or
      activate the export of mRNA molecules harboring both of the inhibitory elements
      and RxRE on the same RNA molecule. Thus, we propose the hypothesis that such
      functions of CIEs may be involved in HTLV-1 persistence.

PMID- 9151841
TI  - Human T cells recovered from human/Balb radiation chimeras are hypersensitive to
      human immunodeficiency virus type 1 infection.
AB  - Replication of human immunodeficiency virus type 1 (HIV-1) is regulated by virus
      encoded regulatory proteins, as well as by a variety of cellular factors.
      Productive infection of human T lymphocytes by HIV-1 is dependent upon the
      activation status of the target cells. In general, short-term mitogenic
      stimulation of CD4 T cells is used to enhance infection of peripheral blood
      mononuclear cells (PBMC) in vitro. Recently, we demonstrated that adoptive
      transfer of human PBMC into lethally irradiated BALB/c mice, radioprotected with
      severe combined immunodeficiency (SCID) mouse bone marrow, leads to marked T-cell
      activation and proliferation. In the present study, we investigated the effect of
      such xenoactivation of human T cells on their susceptibility to HIV-1 infection.
      Human cells that were recovered from human/Balb radiation chimeras supported
      efficient replication of laboratory strains of HIV-1, as well as of HIV-1
      clinical isolates. The multiplicity of infection required to attain effective
      virus replication in the recovered xenoactivated human cells was 10- to 100-fold
      lower than that needed for infection of short- or long-term phytohemagglutinin
      (PHA)-stimulated blasts or of various T-cell lines. Analysis of human cell
      surface activation markers has indicated that xenoactivation in the mouse, in
      contrast to in vitro stimulation with PHA, is associated with a marked
      downregulation of CD25 (interleukin 2 receptor). Our results demonstrate that
      human cells recovered from human/Balb radiation chimeras, which are
      hypersensitive to HIV-1 infection, differ from in vitro-stimulated cells in their
      activation status. Therefore, this system could be used to study host factors
      that participate in HIV-1 infection and replication in vitro and in vivo.

PMID- 9151842
TI  - Derepression of prophage P2 by satellite phage P4: cloning of the P4 epsilon gene
      and identification of its product.
AB  - Escherichia coli phage P4 lacks all of the genetic information necessary for
      capsid, tail, and lysis functions. P4 is therefore dependent on a helper phage,
      such as P2, for lytic propagation. During P4 superinfection of a P2 lysogen, the
      P2 prophage is derepressed by the action of the P4-encoded epsilon gene. We have
      cloned the epsilon gene and identified the 10-kDa E protein. The epsilon gene
      product is the only P4 protein required to derepress prophage P2, which leads to
      in situ P2 DNA replication. A two-plasmid derepression assay system has been
      developed to examine the derepression activity of E. The reporter plasmid
      contains the two face-to-face promoters, Pe and Pc, involved in the lysis
      lysogeny transcriptional switch of phage P2 and the immunity repressor C. The Pe
      promoter is coupled to a cat reporter gene. In the construct, the C repressor is
      transcribed from the Pc promoter and represses the Pe promoter, which mimics the
      in situ-repressed P2 prophage. The E protein is supplied in trans from a
      compatible plasmid in which the epsilon gene is under the control of the T7
      promoter. We show here that in the two-plasmid assay system, induction of the E
      protein derepresses the Pe promoter. The ash9 mutation, which is located upstream
      of the epsilon gene, enhances the E-mediated derepression of the Pe promoter. The
      purified E protein shows no specific DNA binding activity, and the implications
      of this are discussed.

PMID- 9151843
TI  - Baculovirus inhibitor of apoptosis functions at or upstream of the apoptotic
      suppressor P35 to prevent programmed cell death.
AB  - Members of the inhibitor of apoptosis (iap) gene family prevent programmed cell
      death induced by multiple signals in diverse organisms, suggesting that they act
      at a conserved step in the apoptotic pathway. To investigate the molecular
      mechanism of iap function, we expressed epitope-tagged Op-iap, the prototype
      viral iap from Orgyia pseudotsugata nuclear polyhedrosis virus, by using novel
      baculovirus recombinants and stably transfected insect cell lines. Epitope-tagged
      Op-iap blocked both virus- and UV radiation-induced apoptosis. With or without
      apoptotic stimuli, Op-IAP protein (31 kDa) cofractionated with cellular membranes
      and the cytosol, suggesting a cytoplasmic site of action. To identify the step(s)
      at which Op-iap blocks apoptosis, we monitored the effect of Op-iap expression on
      in vivo activation of the insect CED-3/ICE death proteases (caspases). Op-iap
      prevented in vivo caspase-mediated cleavage of the baculovirus substrate
      inhibitor P35 and blocked caspase activity upon viral infection or UV
      irradiation. However, unlike the stoichiometric inhibitor P35, Op-IAP failed to
      affect activated caspase as determined by in vitro protease assays. These
      findings provide the first biochemical evidence that Op-iap blocks activation of
      the host caspase or inhibits its activity by a mechanism distinct from P35.
      Moreover, as suggested by the capacity of Op-iap to block apoptosis induced by
      diverse signals, including virus infection and UV radiation, iap functions at a
      central point at or upstream from steps involving the death proteases.

PMID- 9151844
TI  - Experimental infection of cynomolgus monkeys with simian parvovirus.
AB  - Simian parvovirus is a recently discovered parvovirus that was first isolated
      from cynomolgus monkeys. It is similar to human B19 parvovirus in terms of virus
      genome, tropism for erythroid cells, and characteristic pathology in natural
      infections. Cynomolgus monkeys were infected with simian parvovirus to
      investigate their potential usefulness as an animal model of human B19
      parvovirus. Six adult female cynomolgus monkeys were inoculated with purified
      simian parvovirus by the intravenous or intranasal route and monitored for
      evidence of clinical abnormalities; this included the preparation of complete
      hematological profiles. Viremia and simian parvovirus-specific antibody were
      determined in infected monkeys by dot blot and Western blot assays, respectively.
      Bone marrow was examined at necropsy 6, 10, or 15 days postinfection. All of the
      monkeys developed a smoldering, low-grade viremia that peaked approximately 10 to
      12 days after inoculation. Peak viremia coincided with the appearance of specific
      antibody and was followed by sudden clearance of the virus and complete, but
      transient, absence of reticulocytes from the peripheral blood. Clinical signs
      were mild and involved mainly anorexia and slight weight loss. Infection was
      associated with a mild decrease in hemoglobin, hematocrit, and erythrocyte
      numbers. Bone marrow showed marked destruction of erythroid cells coincident with
      peak viremia. Our findings indicate that infection of healthy monkeys by simian
      parvovirus is self-limited and mild, with transient cessation of erythropoiesis.
      Our study has reproduced Koch's postulates and further shown that simian
      parvovirus infection of monkeys is almost identical to human B19 parvovirus
      infection of humans. Accordingly, this animal model may prove valuable in the
      study of the pathogenesis of B19 virus infection.

PMID- 9151845
TI  - dUTPase-minus caprine arthritis-encephalitis virus is attenuated for pathogenesis
      and accumulates G-to-A substitutions.
AB  - The importance of the virally encoded dUTPase for CAEV replication, invasiveness,
      pathogenesis, and genetic stability was investigated in goats infected by viruses
      with single point (DU-G) and deletion (DU-1) mutations of the dUTPase gene (DU
      gene). The DU gene was found to be dispensable for CAEV replication in vivo as
      judged by times taken to seroconvert, frequencies of viral isolation, and tissue
      distribution of viral RNAs. DU- reversion at week 34 in one of three goats
      infected with the single point mutant DU-G, however, suggested that the viral
      dUTPase confers some advantages for replication in vivo. Moreover, we show that
      dUTPase is necessary for the timely development of bilateral arthritic lesions of
      the carpus. Finally, dUTPase was shown to efficiently prevent accumulation of G
      to-A transitions in the viral genome.

PMID- 9151846
TI  - Murine retroviruses use at least six different receptors for entry into Mus dunni
      cells.
AB  - Murine retroviruses have been divided into six interference groups that use
      different receptors for cell entry: the ecotropic, xenotropic, polytropic,
      amphotropic, 10A1, and Mus dunni endogenous virus groups. Some interference is
      observed between xenotropic and polytropic viruses and between amphotropic and
      10A1 viruses, indicating some overlap in receptor specificity between these
      groups, but otherwise these interference groups appear completely independent. In
      contrast, one study found interference among many of these groups when Mus dunni
      wild mouse cells were examined with an immunofluorescence assay to detect
      infection by the challenge virus. Here we have used a more direct assay for cell
      entry by using pseudotyped retroviral vectors to measure interference in M. dunni
      cells, and we find no evidence for extensive interference between members of
      different murine retrovirus groups. Indeed, our results in M. dunni cells are
      consistent with interference results observed in other cell types and indicate
      that the anomalous interference results previously observed in M. dunni cells
      with the immunofluorescence assay were most likely due to factors other than
      those that affect receptor-mediated virus entry. In summary, our results show
      that murine retroviruses use at least six different receptors for entry into M.
      dunni cells.

PMID- 9151847
TI  - Identification of a novel antiapoptotic functional domain in simian virus 40
      large T antigen.
AB  - The ability of DNA tumor virus proteins to trigger apoptosis in mammalian cells
      is well established. For example, transgenic expression of a simian virus 40
      (SV40) T-antigen N-terminal fragment (N-termTag) is known to induce apoptosis in
      choroid plexus epithelial cells. SV40 T-antigen-induced apoptosis has generally
      been considered to be a p53-dependent event because cell death in the brain is
      greatly diminished in a p53-/- background strain and is abrogated by expression
      of wild-type (p53-binding) SV40 T antigen. We now show that while N-termTags
      triggered apoptosis in rat embryo fibroblasts cultured in low serum, expression
      of full-length T antigens unable to bind p53 [mut(p53-)Tags] protected against
      apoptosis without causing transformation. One domain essential for blocking
      apoptosis by T antigen was mapped to amino acids 525 to 541. This domain has >60%
      homology with a domain of adenovirus type 5 E1B 19K required to prevent E1A
      induced apoptosis. In the context of both wild-type T antigen and mut(p53-)Tags,
      mutation of two conserved amino acids in this region eliminated T antigen's
      antiapoptotic activity in REF-52 cells. These data suggest that SV40 T antigen
      contains a novel functional domain involved in preventing apoptosis independently
      of inactivation of p53.

PMID- 9151848
TI  - Efficient encapsidation of human immunodeficiency virus type 1 vectors and
      further characterization of cis elements required for encapsidation.
AB  - To determine whether there is a cis-acting effect of translational expression of
      gag on RNA encapsidation, we compared the encapsidation of wild-type RNA with
      that of a mutant in which the translation of gag was ablated. This comparison
      indicated that there is not such a cis effect. To determine what is necessary and
      sufficient for encapsidation, we measured the relative encapsidation efficiencies
      of human immunodeficiency virus type 1 vector RNAs containing mutations in
      domains proximal to the canonical encapsidation signal or containing large
      deletions in the remainder of the genome. These data indicate that TAR and two
      additional regions are required for encapsidation and that the 5' end of the
      genome is sufficient for encapsidation. The Rev-responsive element is required
      mainly for efficient RNA transport from the nucleus to the cytoplasm. A foreign
      sequence was found to have a negative effect on encapsidation upon placement
      within the parental vector. Interestingly, this negative effect was compounded by
      multiple copies of the sequence.

PMID- 9151849
TI  - Virus-like particle-induced fusion from without in tissue culture cells: role of
      outer-layer proteins VP4 and VP7.
AB  - We recently described an assay that measures fusion from without induced in
      tissue culture cells by rotavirus, a nonenveloped, triple-protein-layered member
      of the Reoviridae family (M. M. Falconer, J. M. Gilbert, A. M. Roper, H. B.
      Greenberg, and J. S. Gavora, J. Virol. 69:5582-5591, 1995). The conditions
      required for syncytium formation are similar to those for viral penetration of
      the plasma membrane during the course of viral infection of host cells, as the
      presence of the outer-layer proteins VP4 and VP7 and the cleavage of VP4 are
      required. Here we present evidence that virus-like particles (VLPs) produced in
      Spodoptera frugiperda Sf-9 cells from recombinant baculoviruses expressing the
      four structural proteins of rotavirus can induce cell-cell fusion to the same
      extent as native rotavirus. This VLP-mediated fusion activity was dependent on
      trypsinization of VP4, and the strain-specific phenotype of individual VP4
      molecules was retained in the syncytium assay similar to what has been seen with
      reassortant rotaviruses. We show that intact rotavirus and VLPs induce syncytia
      with cells that are permissive to rotavirus infection whereas nonpermissive cells
      are refractory to syncytium formation. This finding further supports our
      hypothesis that the syncytium assay accurately reflects very early events
      involved in viral infection and specifically the events related to viral entry
      into the cell. Our results also demonstrate that neither viral replication nor
      rotavirus proteins other than VP2, VP6, VP4, and VP7 are required for fusion and
      that both VP4 and VP7 are essential. The combination of a cell-cell fusion assay
      and the availability of recombinant VLPs will permit us to dissect the mechanisms
      of rotavirus penetration into host cells.

PMID- 9151850
TI  - The amphotropic murine leukemia virus receptor gene encodes a 71-kilodalton
      protein that is induced by phosphate depletion.
AB  - The amphotropic murine leukemia virus (MuLV) can infect cells from a number of
      mammals, including humans, via its specific receptor. Basic knowledge of
      amphotropic MuLV receptor expression is likely to be useful in the development
      and improvement of gene therapy protocols based on amphotropic-pseudotyped
      vectors. To investigate the expression of the human receptor for the amphotropic
      MuLV (GLVR-2, newly termed Pit2), we determined its mRNA levels in several cell
      lines and found them to vary significantly. Induction of increased levels of mRNA
      after removal of phosphate from the media was observed in two osteosarcoma cell
      lines. The increase in GLVR-2 mRNA resulted in a concomitant rise in the levels
      of a 71-kDa protein specifically recognized by affinity-purified antibodies
      against GLVR-2. Using these antibodies, we were able to confirm the intracellular
      topology of the large hydrophilic domain between the proposed sixth and seventh
      transmembrane domains of the GLVR-2 protein. This assignment is in agreement with
      the fourth extracellular loop being outside the cell, consistent with the
      proposal that the fourth extracellular loop of GLVR-2 contains the envelope
      binding site.

PMID- 9151851
TI  - Role of the extracellular domain of human herpesvirus 7 glycoprotein B in virus
      binding to cell surface heparan sulfate proteoglycans.
AB  - In an attempt to identify the human herpesvirus 7 (HHV-7) envelope protein(s)
      involved in cell surface binding, the extracellular domain of the HHV-7
      glycoprotein B (gB) homolog protein was cloned and expressed as a fusion product
      with the Fc domain of human immunoglobulin G heavy chain gamma1 (gB-Fc) in an
      eukaryotic cell system. Indirect immunofluorescence followed by flow cytometric
      analysis revealed specific binding of gB-Fc to the membrane of SupT1 cells but
      not to other CD4+ T-lymphoblastoid cell lines, such as Jurkat or PM1, clearly
      indicating that gB-Fc did not bind to the CD4 molecule. This was also suggested
      by the ability of gB-Fc to bind to CD4-negative fibroblastoid Chinese hamster
      ovary (CHO) cells. The binding was abrogated by enzymatic removal of cell surface
      heparan sulfate proteoglycans by heparinase and heparitinase but not by treatment
      with condroitinase ABC. In addition, binding of the gB-Fc fusion protein to CHO
      cells was severely impaired in the presence of soluble heparin, as well as when
      heparan sulfate-deficient mutant CHO cells were used. Consistent with these
      findings, soluble heparin was found to block HHV-7 infection and syncytium
      formation in the SupT1 cell line. Although the CD4 antigen is a critical
      component of the receptor for the T-lymphotropic HHV-7, these findings suggest
      that heparin-like molecules also play an important role in HHV-7-cell surface
      interactions required for infection and that gB represents one of the HHV-7
      envelope proteins involved in the adsorption of virus-to-cell surface
      proteoglycans.

PMID- 9151852
TI  - Characterization of the antibody response specific for the human endogenous
      retrovirus HTDV/HERV-K.
AB  - Differentiated human teratocarcinoma cell lines produce the human teratocarcinoma
      derived virus (HTDV) particles encoded by the human endogenous retrovirus
      sequence HERV-K. We screened almost 2,000 human sera for antibodies against this
      endogenous human retrovirus, HTDV/HERV-K. Specificity of the immunofluorescence
      reactions using particle producing teratocarcinoma cells was confirmed by
      immunoelectron microscopy of ultrathin frozen sections. Immunoblot analyses using
      lysates of HTDV-producing cells revealed a 80-kDa HERV-K Gag precursor and a 90
      kDa putative viral Env protein after incubation with positive sera. No processed
      Gag protein could be observed. Virus-specific bands were not detected in lysates
      of nonproducing cells. High antibody titers were found in about 60% of male
      patients with germ cell tumors. Antibody reactivity declined after tumor removal.
      In healthy blood donors, anti-HTDV reactivity was found only at low titers in a
      small percentage (3.9%) of individuals. A slightly elevated but statistically
      significant percentage of HTDV positivity was also observed for sera of pregnant
      women, whereas human immunodeficiency virus-positive individuals exhibited no
      peculiarity compared to normal blood donors. Our results provide evidence that
      HTDV particles are expressed in vivo and that the immune reaction against
      HTDV/HERV-K is specific for defined viral proteins.

PMID- 9151853
TI  - Bone marrow failure by cytomegalovirus is associated with an in vivo deficiency
      in the expression of essential stromal hemopoietin genes.
AB  - Bone marrow (BM) failure associated with cytomegalovirus (CMV) infection is a
      feared complication after clinical BM transplantation. Experiments in long-term
      BM cultures have indicated that BM stromal cells (BMSC) are targets of productive
      CMV infection, but an in situ infection of BM stroma remained to be documented,
      and the pathomechanism is open to question. Here we describe a murine in vivo
      model of lethal CMV aplastic anemia (CMV-AA). The reconstitution of hematopoietic
      progenitor cells expressing stem cell factor (SCF) receptor was found to be
      defective in CMV-AA. While murine CMV replication in permissive parenchymal
      tissues is cytolytic, the hematopoietic cord was found to be a site of very
      limited virus production with foci of reticular BMSC expressing the intranuclear
      viral IE1 protein, but with only a few BMSC positive for viral genome in the in
      situ hybridization. XX-XY BM chimeras were established in order to quantitate Y
      chromosome-tagged BMSC by a PCR specific for the male-sex-determining gene Tdy.
      This approach revealed that murine CMV infection is not associated with a
      significant loss of BMSC. Despite the physical integrity of the stromal network,
      the functional integrity of the stroma was impaired. While housekeeping genes
      were expressed normally in BMSC of infected mice, the expression of genes
      encoding the essential hemopoietins SCF, granulocyte colony-stimulating factor,
      and interleukin-6 was markedly reduced. In conclusion, the mechanism of BM
      failure is not a stromal lesion but an insufficient stromal function. These
      findings explain CMV-AA as a manifestation of multiple hemopoietin deficiency.

PMID- 9151854
TI  - The major immediate-early proteins IE1 and IE2 of human cytomegalovirus
      colocalize with and disrupt PML-associated nuclear bodies at very early times in
      infected permissive cells.
AB  - The major immediate-early (MIE) gene products of human cytomegalovirus (HCMV) are
      nuclear phosphoproteins that are thought to play key roles in initiating lytic
      cycle gene regulation pathways. We have examined the intranuclear localization
      pattern of both the IE1 and IE2 proteins in virus-infected and DNA-transfected
      cells. When HCMV-infected human diploid fibroblast (HF) cells were stained with
      specific monoclonal antibodies, IE1 localized as a mixture of nuclear diffuse and
      punctate patterns at very early times (2 h) but changed to an exclusively nuclear
      diffuse pattern at later times. In contrast, IE2 was distributed predominantly in
      nuclear punctate structures continuously from 2 to at least 12 h after infection.
      These punctate structures resembled the preexisting PML-associated nuclear bodies
      (ND10 or PML oncogenic domains [PODs]) that are disrupted and dispersed by the
      IE110 protein as a very early event in herpes simplex virus (HSV) infection.
      However, HCMV differed from HSV by leading instead to a change in both the PML
      and SP100 protein distribution from punctate bodies to uniform diffuse patterns,
      a process that was complete in 50% of the cells at 2 h and in 90% of the cells by
      4 h after infection. Confocal double-label indirect immunofluorescence assay
      analysis confirmed that both IE1 and IE2 colocalized transiently with PML in
      punctate bodies at very early times after infection. In transient expression
      assays, introduction of IE1-encoding plasmid DNA alone into Vero or HF cells
      produced the typical total redistribution of PML into a uniform nuclear diffuse
      pattern together with the IE1 protein, whereas introduction of IE2-encoding
      plasmid DNA alone resulted in stable colocalization of the IE2 protein with PML
      in the PODs. A truncated mutant form of IE1 gave large nuclear aggregates and
      failed to redistribute PML, and similarly a deleted mutant form of IE2 failed to
      colocalize with the punctate PML bodies, confirming the specificity of these
      effects. Furthermore, both Vero and U373 cell lines constitutively expressing IE1
      also showed total PML relocalization together with the IE1 protein into a nuclear
      diffuse pattern, although a very small percentage of the cells which failed to
      express IE1 reverted to a punctate PML pattern. Finally, the PML redistribution
      activity of IE1 and the direct association of IE2 with PML punctate bodies were
      both confirmed by infection with E1A-negative recombinant adenovirus vectors
      expressing either IE1 or IE2 alone. These results confirm that transient
      colocalization with and disruption of PML-associated nuclear bodies by IE1 and
      continuous targeting to PML-associated nuclear bodies by IE2 are intrinsic
      properties of these two MIE regulatory proteins, which we suggest may represent
      critical initial events for efficient lytic cycle infection by HCMV.

PMID- 9151855
TI  - The herpes simplex virus immediate-early protein ICP0 affects transcription from
      the viral genome and infected-cell survival in the absence of ICP4 and ICP27.
AB  - ICP4, ICP0, and ICP27 are the immediate-early (IE) regulatory proteins of herpes
      simplex virus that have the greatest effect on viral gene expression and growth.
      Comparative analysis of viral mutants defective in various subsets of these IE
      genes should help elucidate how these proteins affect cellular and viral
      processes. This study focuses on the mutant d97, which is defective for the genes
      encoding ICP4, ICP0, and ICP27 and expresses the bacterial beta-galactosidase
      (beta-gal) gene from the ICP0 promoter. Together with the d92 virus (ICP4- ICP27
      ) and the ICP0-complementing cell line L7, d97 provided a unique opportunity to
      evaluate ICP0 function in the absence of the regulatory activities specified by
      ICP4 and ICP27. The pattern of protein synthesis in d97-infected cells was unique
      relative to other IE gene mutants in that it was similar to that seen in the
      absence of prior viral protein synthesis, possibly approximating the effect of
      cellular factors and virion components alone. Inactivation of ICP0 in the absence
      of ICP4 produced a significant decrease in the levels of the early mRNAs ICP6 and
      thymidine kinase (tk). There was also a marginal reduction in the levels of the
      IE ICP22 mRNA, and this was most notable at low multiplicity of infection (MOI).
      In d97-infected L7 cells, the levels of the viral mRNAs were mostly restored to
      those observed in infections with d92. Nuclear runoff transcription analysis
      demonstrated that the presence of ICP0 resulted in an increase in the
      transcription rates of the analyzed genes. The transcription rates of the early
      genes were dramatically reduced in the absence of ICP0. At low MOI, the
      transcription rates of ICP6 and tk were comparable to the rate of transcription
      of a cellular gene. Relevant to the potential use of d97 as a transfer vector, it
      was also determined that the absence of ICP0 reduced the cellular toxicity of the
      virus compared to that of d92. The beta-gal transgene expressed from an IE
      promoter was detected for up to 14 days postinfection; however, the level of beta
      gal expression declined dramatically after 1 day postinfection. In the presence
      of ICP0, the level of expression of beta-gal was increased; however the infected
      monolayer was destroyed by 3 days postinfection. Therefore, deletion of ICP0 in
      the absence of ICP4 and ICP27 reduces toxicity and lowers the level of expression
      of genes from the viral genome.

PMID- 9151856
TI  - Long-term gene delivery into the livers of immunocompetent mice with E1/E4
      defective adenoviruses.
AB  - We have compared the in vitro and in vivo behaviors of a set of isogenic E1- and
      E1/E4-defective adenoviruses expressing the lacZ gene of Escherichia coli from
      the Rous sarcoma virus long terminal repeat. Infection of tumor-derived
      established cell lines of human origin with the doubly defective adenoviruses
      resulted in (i) a lower replication of the viral backbone that correlated with
      reduced levels of E2A-specific RNA and protein, (ii) a significant shutoff of
      late gene and protein expression, and (iii) no apparent virus-induced
      cytotoxicity. Independently of the extent of the deletion, the additional
      inactivation of E4 from the viral backbone therefore drastically disabled the
      virus in vitro, with no apparent effect on transgene expression. A lacZ
      transgenic model was used to compare the different recombinant adenoviruses in
      the livers of C57BL/6 mice. The immune response to the virally encoded beta
      galactosidase was minimal in this model, as infusion of the E1-defective
      adenovirus resulted in a time course of transgene expression that mimicked that
      in immunodeficient (nu/nu) mice, with very little inflammation and necrosis in
      the liver. Administration of a doubly defective adenovirus to the transgenic
      animals led to long-term extrachromosomal persistence of viral DNA in the liver,
      with no detectable methylation of CpG dinucleotides. However, transient transgene
      expression was observed independently of the extent of the E4 deletion,
      suggesting that the choice of the promoter may be critical to maintain transgene
      expression from these attenuated adenovirus vectors.

PMID- 9151857
TI  - Induction of the transcription factor Sp1 during human cytomegalovirus infection
      mediates upregulation of the p65 and p105/p50 NF-kappaB promoters.
AB  - During human cytomegalovirus (HCMV) infection, the promoters for the classical NF
      kappaB subunits (p65 and p105/p50) are transactivated. Previously, we
      demonstrated that the viral immediate-early (IE) proteins (IE1-72, IE2-55, and
      IE2-86) were involved in this upregulation. These viral factors alone, however,
      could not account for the entirety of the increased levels of transcription.
      Because one of the hallmarks of HCMV infection is the induction of cellular
      transcription factors, we hypothesized that one or more of these induced factors
      was also critical to the regulation of NF-kappaB during infection. Sp1 was one
      such factor that might be involved because p65 promoter activity was upregulated
      by Sp1 and both of the NF-kappaB subunit promoters are GC rich and contain Sp1
      binding sites. Therefore, to detail the role that Sp1 plays in the regulation of
      NF-kappaB during infection, we initially examined Sp1 levels for changes during
      infection. HCMV infection resulted in increased Sp1 mRNA expression, protein
      levels, and DNA binding activity. Because both promoters were transactivated by
      Sp1, we reasoned that the upregulation of Sp1 played a role in p65 and p105/p50
      promoter activity during infection. To address the specific role of Sp1 in p65
      and p105/p50 promoter transactivation by HCMV, we mutated both promoters. These
      results demonstrated that the Sp1-specific DNA binding sites were involved in the
      virus-mediated transactivation. Last, to further dissect the role of HCMV in the
      Sp1-mediated induction of NF-kappaB, we examined the role that the viral IE genes
      played in Sp1 regulation. The IE gene products (IE1-72, IE2-55, and IE2-86)
      cooperated with Sp1 to increase promoter transactivation and physically
      interacted with Sp1. In addition, the IE2-86 product increased Sp1 DNA binding by
      possibly freeing up inactive Sp1. These data supported our hypothesis that Sp1
      was involved in the upregulation of NF-kappaB during HCMV infection through the
      Sp1 binding sites in the p65 and p105/p50 promoters and additionally demonstrated
      a potential viral mechanism that might be responsible for the upregulation of Sp1
      activity.

PMID- 9151858
TI  - Characterization of LMP-1's association with TRAF1, TRAF2, and TRAF3.
AB  - The latent membrane protein 1 (LMP-1) of Epstein-Barr virus (EBV) contributes to
      the immortalizing activity of EBV in primary, human B lymphocytes. LMP-1 is
      targeted to the plasma membrane, where it influences signaling pathways of
      infected cells. LMP-1 has been found to associate with members of the tumor
      necrosis factor receptor-associated factor (TRAF) family of proteins. As with LMP
      1, the TRAF molecules have been shown to participate in cell signaling pathways.
      We have characterized and mapped in detail a region of LMP-1 that associates with
      TRAF1, TRAF2, and TRAF3. TRAF3 alone associates with LMP-1 in a yeast two-hybrid
      assay, whereas all three TRAF molecules associate with LMP-1 under various
      conditions when they are assayed in extracts of human cells. TRAF1, TRAF2, and
      TRAF3 appear to associate independently with LMP-1 but bind an overlapping target
      site. TRAF3 associates with LMP-1 most avidly and can compete with TRAF1 and
      TRAF2 for binding to LMP-1. TRAF2 associates with truncated derivatives of the
      carboxy terminus of LMP-1 more efficiently than with the intact terminus,
      indicating that LMP-1's conformation may regulate its association with TRAF2.
      Finally, point mutations that decrease LMP-1's association with the three TRAF
      molecules to 3 to 20% of wild-type levels do not detectably affect otherwise
      intact LMP-1's induction of NF-kappaB activity. Therefore, these associations are
      not necessary for the majority of intact LMP-1's induction of this signaling
      pathway.

PMID- 9151860
TI  - Molecular cloning of Mus dunni endogenous virus: an unusual retrovirus in a new
      murine viral interference group with a wide host range.
AB  - Mus dunni endogenous virus (MDEV) is activated from cells of the Asian wild mouse
      M. dunni (also known as Mus terricolor) in response to treatment with either 5
      iodo-2'-deoxyuridine or hydrocortisone. MDEV represents a new murine retrovirus
      interference group and thus appears to use a different receptor for entry into
      cells than do other murine retroviruses. Here we show that MDEV is also not in
      the gibbon ape leukemia virus or RD114 virus interference groups. A retroviral
      vector with an MDEV pseudotype was capable of efficiently infecting a wide
      variety of cells from different species, indicating that the MDEV receptor is
      widely expressed. We isolated a molecular clone of this virus which exhibited no
      hybridization to any cloned retrovirus examined, suggesting that MDEV has an
      unusual genome. One copy of a possible retrovirus element that weakly hybridized
      with MDEV was present in the genomes of laboratory strains of mice, while no such
      elements were present in other species examined. A virus activated by 5-iodo-2'
      deoxyuridine from cells of a BALB/c mouse, however, was not related to MDEV by
      either hybridization or interference analyses.

PMID- 9151859
TI  - Epstein-Barr virus uses HLA class II as a cofactor for infection of B
      lymphocytes.
AB  - Infection of B lymphocytes by Epstein-Barr virus (EBV) requires attachment of
      virus via binding of viral glycoprotein gp350 to CD21 on the cell surface.
      Penetration of the cell membrane additionally involves a complex of three
      glycoproteins, gH, gL, and gp42. Glycoprotein gp42 binds to HLA-DR. Interference
      with this interaction with a soluble form of gp42, with a monoclonal antibody
      (MAb) to gp42, or with a MAb to HLA-DR inhibited virus infection. It was not
      possible to superinfect cells that failed to express HLA-DR unless expression was
      restored by transfection or creation of hybrid cell lines with complementing
      deficiencies in expression of HLA class II. HLA class II molecules thus serve as
      cofactors for infection of human B cells.

PMID- 9151861
TI  - The cytotoxicity of the parvovirus minute virus of mice nonstructural protein NS1
      is related to changes in the synthesis and phosphorylation of cell proteins.
AB  - Autonomous parvoviruses exert lytic and cytostatic effects believed to contribute
      to their antineoplastic activity. Studies with inducible clones have demonstrated
      a direct involvement of parvovirus nonstructural proteins (NS) in oncolysis.
      Human and rat fibroblasts have been stably transfected with MVM(p) (minute virus
      of mice prototype strain) NS genes cloned under the control of a hormone
      inducible promoter. Dexamethasone-induced synthesis of the NS proteins in
      sensitive transformed cells results in cell killing within a few days. From these
      sensitive cell lines have been isolated some NS-resistant clones that also prove
      resistant to MVM(p) infection, suggesting that cell factors modulate NS
      cytotoxicity. We have previously reported that factors involved in cell cycle
      regulation may contribute to this modulation, since NS toxicity requires cell
      proliferation and correlates with a cell cycle perturbation leading to an arrest
      in phase S/G2. In addition to its role in cytotoxicity, NS1 can regulate
      transcription driven by parvovirus and nonparvovirus promoters. Since
      phosphorylation is a critical event in controlling the activity of many proteins,
      notably transcription factors and cell cycle-regulated proteins, we have examined
      the effect of NS1 on the synthesis and phosphorylation of cell proteins. Our
      results indicate that NS1 interferes, within 7 h of induction, with
      phosphorylation of a protein of about 14 kDa (p14). Cell synchronization has
      enabled us to show that phosphorylation of this protein occurs in early S phase
      and is prevented when NS1 is induced. This early effect of NS1 on p14
      phosphorylation may be directly linked to cytotoxicity and is probably related to
      the previously reported inhibition of cell DNA synthesis. Late in the induction
      period (24 h), NS1 also alters the synthesis of a 50-kDa protein and a 35-kDa
      protein (p50 and p35, respectively). Microsequencing of p35 reveals sequence
      homology with beta-tubulin. These effects of NS1, observed only in NS1-sensitive
      cell lines, may be related to the protein's cytotoxicity.

PMID- 9151862
TI  - Poliovirus infection and expression of the poliovirus protein 2B provoke the
      disassembly of the Golgi complex, the organelle target for the antipoliovirus
      drug Ro-090179.
AB  - Infection of Vero cells with poliovirus results in complete disassembly of the
      Golgi complex. Milestones of the process of disassembly are the release to the
      cytosol of the beta-COP bound to Golgi membranes, the disruption of the cis-Golgi
      network into fragments scattered throughout the cytoplasm, and the disassembly of
      the stacked cisternae by a process mediated by long tubular structures. Transient
      expression of the viral protein 2B in COS-7 cells also causes the disassembly of
      the Golgi complex by a process preceded by the accumulation of the protein in the
      Golgi area. Vero cells infected for 3 h show no recognizable Golgi complexes at
      the ultrastructural level and display an enormously swollen endoplasmic reticulum
      (ER) with extensive areas of its surface heavily coated. Ro-090179 (Ro), a
      flavonoid isolated from the herb Agastache rugosa, provokes the specific swelling
      and disruption of the Golgi complex and strongly inhibits poliovirus infection.
      Ro provokes the swelling and the disruption of the stacked cisternae and trans
      Golgi elements without affecting the cis-most Golgi cisternae much. Moreover, Ro
      inhibits the fusion of the Golgi complex with the ER in cells treated with
      brefeldin A and provokes the accumulation of the intermediate compartment
      membrane protein p58 into ERD2-positive Golgi elements but has no effect on the
      anterograde transport involved in protein secretion. Our results indicate that
      the secretory pathway and specifically the Golgi complex are preferential targets
      of poliovirus.

PMID- 9151863
TI  - Evolution of human immunodeficiency virus type 1 in perinatally infected infants
      with rapid and slow progression to disease.
AB  - We addressed the relationship between the origin and evolution of human
      immunodeficiency virus type 1 (HIV-1) variants and disease outcome in perinatally
      infected infants by studying the V3 regions of viral variants in samples obtained
      from five transmitting mothers at delivery and obtained sequentially over the
      first year of life from their infected infants, two of whom (rapid progressors)
      rapidly progressed to having AIDS. Phylogenetic analyses disclosed that the V3
      sequences from each mother-infant pair clustered together and were clearly
      distinct from those of the other pairs. Within each pair, the child's sequences
      formed a monophyletic group, indicating that a single variant initiated the
      infection in both rapid and slow progressors. Plasma HIV-1 RNA levels increased
      in all five infants during their first months of life and then declined within
      the first semester of life only in the three slow progressors. V3 variability
      increased over time in all infants, but no differences in the pattern of V3
      evolution in terms of potential viral phenotype were observed. The numbers of
      synonymous and nonsynonymous substitutions varied during the first semester of
      life regardless of viral load, CD4+-cell count, and disease progression.
      Conversely, during the second semester of life the rate of nonsynonymous
      substitutions was higher than that of synonymous substitutions in the slow
      progressors but not in the rapid progressors, thus suggesting a stronger host
      selective pressure in the former. In view of the proposal that V3 genetic
      evolution is driven mainly by host immune constraints, these findings suggest
      that while the immune response to V3 might contribute to regulating viral levels
      after the first semester of life, it is unlikely to play a determinant role in
      the initial viral decline soon after birth.

PMID- 9151864
TI  - RevM10-expressing T cells derived in vivo from transduced human hematopoietic
      stem-progenitor cells inhibit human immunodeficiency virus replication.
AB  - A key feature of the pathogenesis of human immunodeficiency virus type 1 (HIV-1)
      infection is the gradual loss of CD4-positive T cells. A number of gene therapy
      strategies have been designed with the intent of inhibiting HIV replication in
      mature T cells. As T cells are products of hematolymphoid differentiation,
      insertion of antiviral genes into hematopoietic stem cells could serve as a
      vehicle to confer long-term protection in progeny T cells derived from transduced
      stem cells. One such "cellular immunization" strategy utilizes the gene coding
      for the HIV-1 rev trans-dominant mutant protein RevM10 which has been
      demonstrated to inhibit HIV-1 replication in T-cell lines and in primary T cells.
      In this study, we used a Moloney murine leukemia virus-based retrovirus encoding
      a bicistronic message coexpressing RevM10 and the murine CD8-alpha' chain (Lyt2).
      This vector allows rapid selection of transgene-expressing cells as well as
      quantitation of transgene expression. We demonstrate that RevM10-transduced CD34
      enriched hematopoietic progenitor-stem cells (HPSC) isolated from human umbilical
      cord blood or from granulocyte colony-stimulating factor-mobilized peripheral
      blood can give rise to mature thymocytes in the SCID-hu thymus/liver mouse model.
      The phenotypic distribution of HPSC-derived thymocytes is normal, and expression
      of the transgene can be detected by flow cytometric analysis. Moreover, we
      demonstrate that RevM10 can inhibit HIV replication in T cells derived from
      transduced HPSC after expansion in vitro. This is the first demonstration of anti
      HIV efficacy in T cells derived from transduced human HPSC.

PMID- 9151865
TI  - A retention signal necessary and sufficient for Golgi localization maps to the
      cytoplasmic tail of a Bunyaviridae (Uukuniemi virus) membrane glycoprotein.
AB  - Members of the Bunyaviridae family mature by a budding process in the Golgi
      complex. The site of maturation is thought to be largely determined by the
      accumulation of the two spike glycoproteins, G1 and G2, in this organelle. Here
      we show that the signal for localizing the Uukuniemi virus (a phlebovirus) spike
      protein complex to the Golgi complex resides in the cytoplasmic tail of G1. We
      constructed chimeric proteins in which the ectodomain, transmembrane domain
      (TMD), and cytoplasmic tail (CT) of Uukuniemi virus G1 were exchanged with the
      corresponding domains of either vesicular stomatitis virus G protein (VSV G),
      chicken lysozyme, or CD4, all proteins readily transported to the plasma
      membrane. The chimeras were expressed in HeLa or BHK-21 cells by using either the
      T7 RNA polymerase-driven vaccinia virus system or the Semliki Forest virus
      system. The fate of the chimeric proteins was monitored by indirect
      immunofluorescence, and their localizations were compared by double labeling with
      markers specific for the Golgi complex. The results showed that the ectodomain
      and TMD (including the 10 flanking residues on either side of the membrane) of G1
      played no apparent role in targeting chimeric proteins to the Golgi complex.
      Instead, all chimeras containing the CT of G1 were efficiently targeted to the
      Golgi complex and colocalized with mannosidase II, a Golgi-specific enzyme.
      Conversely, replacing the CT of G1 with that from VSV G resulted in the efficient
      transport of the chimeric protein to the cell surface. Progressive deletions of
      the G1 tail suggested that the Golgi retention signal maps to a region
      encompassing approximately residues 10 to 50, counting from the proposed border
      between the TMD and the tail. Both G1 and G2 were found to be acylated, as shown
      by incorporation of [3H]palmitate into the viral proteins. By mutational analyses
      of CD4-G1 chimeras, the sites for palmitylation were mapped to two closely spaced
      cysteine residues in the G1 tail. Changing either or both of these cysteines to
      alanine had no effect on the targeting of the chimeric protein to the Golgi
      complex.

PMID- 9151866
TI  - Cold-adapted poliovirus mutants bypass a postentry replication block.
AB  - In the current model of poliovirus entry, the initial interaction of the native
      virion with its cellular receptor is followed by a transition to an altered form,
      which then acts as an intermediate in viral entry. While the native virion
      sediments at 160S in a sucrose gradient, the altered particle sediments at 135S,
      has lost the coat protein VP4, and has become more hydrophobic. Altered particles
      can be found both associated with cells and in the culture medium. It has been
      hypothesized that the cell-associated 135S particle releases the viral genome
      into the cell cytoplasm and that nonproductive transitions to the 135S form are
      responsible for the high particle-to-PFU ratio observed for polioviruses. At 25
      degrees C, a temperature at which the transition to 135S particles does not
      occur, the P1/Mahoney strain of poliovirus was unable to replicate, and cold
      adapted (ca) mutants were selected from the population. These mutants have not
      gained the ability to convert to 135S particles at 25 degrees C, and the block to
      wild-type (wt) infection at low temperatures is not at the level of cellular
      entry. The particle-to-PFU ratio of poliovirus does not change at 25 degrees C in
      the absence of alteration. Three independent amino acid changes in the 2C coding
      region were identified in ca mutants, at positions 218 (Val to Ile), 241 (Arg to
      Ala), and 309 (Met to Val). Introduction of any of these mutations individually
      into wt poliovirus by site-directed mutagenesis confers the ca phenotype. All
      three serotypes of the Sabin vaccine strains and the P3/Leon strain of poliovirus
      also exhibit the ca phenotype. These results do not support a model of poliovirus
      entry into cells that includes an obligatory transition to the 135S particle.

PMID- 9151867
TI  - Coxsackievirus A21 binds to decay-accelerating factor but requires intercellular
      adhesion molecule 1 for cell entry.
AB  - It is becoming increasingly apparent that many viruses employ multiple receptor
      molecules in their cell entry mechanisms. The human enterovirus coxsackievirus
      A21 (CAV21) has been reported to bind to the N-terminal domain of intercellular
      adhesion molecule 1 (ICAM-1) and undergo limited replication in ICAM-1-expressing
      murine L cells. In this study, we show that in addition to binding to ICAM-1,
      CAV21 binds to the first short consensus repeat (SCR) of decay-accelerating
      factor (DAF). Dual antibody blockade using both anti-ICAM-1 (domain 1) and anti
      DAF (SCR1) monoclonal antibodies (MAbs) is required to completely abolish binding
      and replication of high-titered CAV21. However, the binding of CAV21 to DAF,
      unlike that to ICAM-1, does not initiate a productive cell infection. The
      capacity of an anti-DAF (SCR3) MAb to block CAV21 infection but not binding,
      coupled with immunoprecipitation data from chemical cross-linking studies,
      indicates that DAF and ICAM-1 are closely associated on the cell surface. It is
      therefore suggested that DAF may function as a low-affinity attachment receptor
      either enhancing viral presentation or providing a viral sequestration site for
      subsequent high-affinity binding to ICAM-1.

PMID- 9151868
TI  - Role of the first and third extracellular domains of CXCR-4 in human
      immunodeficiency virus coreceptor activity.
AB  - The CXCR-4 chemokine receptor and CD4 behave as coreceptors for cell line-adapted
      human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and for dual-tropic
      HIV strains, which also use the CCR-5 coreceptor. The cell line-adapted HIV-1
      strains LAI and NDK and the dual-tropic HIV-2 strain ROD were able to infect CD4+
      cells expressing human CXCR-4, while only LAI was able to infect cells expressing
      the rat homolog of CXCR-4. This strain selectivity was addressed by using human
      rat CXCR-4 chimeras. All chimeras tested mediated LAI infection, but only those
      containing the third extracellular domain (e3) of human CXCR-4 mediated NDK and
      ROD infection. The e3 domain might be required for the functional interaction of
      NDK and ROD, but not LAI, with CXCR-4. Alternatively, LAI might also interact
      with e3 but in a different way. Monoclonal antibody 12G5, raised against human
      CXCR-4, did not stain cells expressing rat CXCR-4. Chimeric human-rat CXCR-4
      allowed us to map the 12G5 epitope in the e3 domain. The ability of 12G5 to
      neutralize infection by certain HIV-1 and HIV-2 strains is also consistent with
      the role of e3 in the coreceptor activity of CXCR-4. The deletion of most of the
      amino-terminal extracellular domain (e1) abolished the coreceptor activity of
      human CXCR-4 for ROD and NDK but not for LAI. These results indicate that HIV
      strains have different requirements for their interaction with CXCR-4. They also
      suggest differences in the interaction of dual-tropic HIV with CCR-5 and CXCR-4.

PMID- 9151869
TI  - Epstein-Barr virus latent membrane protein 2 associates with and is a substrate
      for mitogen-activated protein kinase.
AB  - The latent membrane protein 2 (LMP2) of Epstein-Barr virus interferes with B
      lymphocyte signal transduction through the immunoglobulin (Ig) receptor. Two
      isoforms of LMP2 exist and differ only in that one isoform (LMP2a) contains an N
      terminal cytoplasmic domain that the other isoform does not. LMP2a is a
      phosphoprotein that is phosphorylated on tyrosines and serines in the cytoplasmic
      domain. GST1-119, a glutathione S-transferase (GST) fusion protein containing the
      119 amino acids of the cytoplasmic domain, affinity precipitated serine kinase
      activity from BJAB cell extracts. The affinity-precipitated kinase phosphorylated
      LMP2a sequences, and kinase activity was increased following induction. Probing
      of Western immunoblots of affinity-precipitated proteins showed that the Erk1
      form of mitogen-activated protein kinase (MAPK) was present. Purified MAPK
      phosphorylated GST fusion proteins containing the cytoplasmic domain of LMP2a and
      mutational analyses were used to identify S15 and S102 as the sites of in vitro
      phosphorylation. A polyclonal rabbit antiserum was prepared against a maltose
      binding protein-LMP2a cytoplasmic domain fusion protein (MBP1-119) and used to
      immunoprecipitate LMP2a from the in vitro-immortalized lymphoblastoid B-cell line
      B95-8CR. LMP2a immunoprecipitates from B95-8CR contained MAPK as a coprecipitated
      protein. Cross-linking surface Ig on B95-8CR cells failed to induce MAPK activity
      within the cells. Treatment of B95-8CR with phorbol myristate acetate (PMA) was
      able to bypass the Ig receptor block and activate MAPK activity. Phosphorylation
      of LMP2a on serine residues increased after PMA induction. The possible role for
      LMP2a serine phosphorylation by MAPK in the control of latency is discussed.

PMID- 9151870
TI  - Tempo and mode of nucleotide substitutions in gag and env gene fragments in human
      immunodeficiency virus type 1 populations with a known transmission history.
AB  - The complex evolutionary process of human immunodeficiency virus type 1 (HIV-1)
      is marked by a high level of genetic variation. It has been shown that the HIV-1
      genome is characterized by variable and more constant regions, unequal nucleotide
      frequencies, and preference for G-to-A substitutions. However, this knowledge has
      largely been neglected in phylogenetic analyses of HIV-1 nucleotide sequences,
      even though these analyses are applied to a number of important biological
      questions. The purpose of this study was to identify a realistic model of HIV-1
      evolution and to statistically test if the application of such a model
      significantly improves the accuracy of phylogenetic analyses. A unique and
      recently reported HIV-1 transmission cluster consisting of nine infected
      individuals, for whom the direction and time for each transmission were exactly
      known, formed the basis for the analyses which were performed under a general
      model of nucleotide substitution using population sequences from the env V3 and
      p17gag regions of the HIV-1 genome. Examination of seven different substitution
      models by maximum-likelihood methods revealed that the fit of the general
      reversible (REV) model was significantly better than that of simpler models,
      indicating that it is important to account for the asymmetric substitution
      pattern of HIV-1 and that the nucleotide substitution rate varied significantly
      across sites. The shape parameter alpha, which describes the variation across
      sites by a gamma distribution, was estimated to be 0.38 and 0.25 for env V3 and
      p17gag, respectively. In env V3, the estimated average transition/transversion
      rate ratio was 1.42. Thus, the REV model with variable rates across sites
      (described by a gamma distribution) provides the best description of HIV-1
      evolution, whereas simple models are unrealistic and inaccurate. It is likely
      that the accuracy of phylogenetic studies of HIV-1 and many other viruses would
      improve substantially by the use of more realistic nucleotide substitution
      models. This is especially true when attempts are made to estimate the age of
      distant viral ancestors from contemporary viral sequences.

PMID- 9151872
TI  - Selective targeting of human cells by a chimeric adenovirus vector containing a
      modified fiber protein.
AB  - The adenovirus fiber protein is responsible for attachment of the virion to
      unidentified cell surface receptors. There are at least two distinct adenovirus
      fiber receptors which interact with the group B (Ad3) and group C (Ad5)
      adenoviruses. We have previously shown by using expressed adenovirus fiber
      proteins that it is possible to change the specificity of the fiber protein by
      exchanging the head domain with another serotype which recognizes a different
      receptor (S. C. Stevenson et al., J. Virol. 69:2850-2857, 1995). A chimeric fiber
      cDNA containing the Ad3 fiber head domain fused to the Ad5 fiber tail and shaft
      was incorporated into the genome of an adenovirus vector with E1 and E3 deleted
      encoding beta-galactosidase to generate Av9LacZ4, an adenovirus particle which
      contains a chimeric fiber protein. Western blot analysis of the chimeric fiber
      vector confirmed expression of the chimeric fiber protein and its association
      with the adenovirus capsid. Transduction experiments with fiber protein
      competitors demonstrated the altered receptor tropism of the chimeric fiber
      vector compared to that of the parental Av1LacZ4 vector. Transduction of a panel
      of human cell lines with the chimeric and parental vectors provided evidence for
      a different cellular distribution of the Ad5 and Ad3 receptors. Three cell lines
      (THP-1, MRC-5, and FaDu) were more efficiently transduced by the vector
      containing the Ad3 fiber head than by the Ad5 fiber vector. In contrast, human
      coronary artery endothelial cells were transduced more readily with the vector
      containing the Ad5 fiber than with the chimeric fiber vector. HeLa and human
      umbilical vein endothelial cells were transduced at equivalent levels compared
      with human diploid fibroblasts, which were refractory to transduction with both
      vectors. These results provide evidence for the differential expression of the
      Ad5 and Ad3 receptors on human cell lines derived from clinically relevant target
      tissues. Furthermore, we show that exchange of the fiber head domain is a viable
      approach to the production of adenovirus vectors with cell-type-selective
      transduction properties. It may be possible to extend this approach to the use of
      ligands for a range of different cellular receptors in order to target gene
      transfer to specific cell types at the level of transduction.

PMID- 9151871
TI  - Herpes simplex virus type 1 prereplicative sites are a heterogeneous population:
      only a subset are likely to be precursors to replication compartments.
AB  - When herpes simplex virus type 1 (HSV-1) DNA replication is blocked by viral
      polymerase inhibitors, such as phosphonoacetic acid (PAA) or acyclovir (ACV),
      UL29 (ICP8) localizes to numerous punctate nuclear foci which are called
      prereplicative sites. Since this pattern can form in cells infected with mutants
      which are defective in UL5, UL8, UL9, or UL52 in the presence of polymerase
      inhibitors (C. J. Lukonis and S. K. Weller, J. Virol. 70:1751-1758, 1996; L. M.
      Liptak, S. L. Uprichard, and D. M. Knipe, J. Virol. 70:1759-1767, 1996), we
      previously proposed that it is unlikely that these numerous UL29 foci actually
      represent a functional subassembly of viral replication proteins that could lead
      to the formation of replication compartments (C. J. Lukonis and S. K. Weller, J.
      Virol. 70:1751-1758, 1996). In this paper, we have investigated the requirement
      for formation of the prereplicative site pattern by using double mutants of HSV.
      From the analysis of mutants lacking both UL5 and UL9, we conclude that neither
      viral helicase is required for the prereplicative site pattern to form as long as
      a polymerase inhibitor is present. From the analysis of mutants defective in both
      UL30 and UL5, we suggest that the prereplicative site pattern can form under
      conditions in which viral and/or cellular polymerases are inhibited. Furthermore,
      reexamination of the UL29 staining pattern in cells infected with wild-type virus
      in the presence of PAA reveals that at least two different UL29 staining patterns
      can be detected in these cells. One population of cells contains numerous
      (greater than 20) punctate UL29 foci which are sites of cellular DNA synthesis.
      In another population of cells, fewer punctate foci (less than 15) are detected,
      and these structures do not colocalize with sites of cellular DNA synthesis.
      Instead, they colocalize with PML, a component of nuclear matrix structures known
      as ND10. We propose that ND10-associated UL29 sites represent domains at which
      replication compartments form.

PMID- 9151873
TI  - Open reading frame 26 of human herpesvirus 8 encodes a tetradecanoyl phorbol
      acetate- and butyrate-inducible 32-kilodalton protein expressed in a body cavity
      based lymphoma cell line.
AB  - DNA sequences corresponding to a novel herpesvirus (human herpesvirus 8 [HHV8])
      are associated with Kaposi's sarcoma (KS), Castleman's disease, and body cavity
      based lymphomas (BCBL). Studies of a BCBL-derived cell line suggest a direct
      correlation between seropositivity against antigens specifically present in such
      lines and the development of KS. We have generated recombinant proteins
      corresponding to open reading frame (ORF) 26 of HHV8 and have produced affinity
      purified antibodies. Using these antibodies, we studied the expression of HHV8
      ORF26 in a BCBL-derived cell line and found that it encodes a cytoplasmic protein
      whose expression is induced 16-fold by treatment with phorbol ester or sodium
      butyrate. This protein induction correlates with a significant induction of viral
      RNA transcripts. Interestingly, under our experimental conditions minimal
      increases in viral DNA were observed. No antibodies to the ORF26 protein of HHV8
      were found in the sera from two human immunodeficiency virus-positive patients
      with KS as determined by immunoprecipitation analysis. However, antibodies in the
      sera from the two KS patients immunoprecipitated a 34-kDa protein found in
      extracts from induced BCBL1 cells that was not recognized by the control sera.

PMID- 9151874
TI  - Diminishing adenovirus gene expression and viral replication by promoter
      replacement.
AB  - The adenovirus E4 promoter was replaced by a synthetic promoter composed of a
      minimal TATA box and five consensus 17-mer yeast GAL4-binding-site elements. The
      viral vectors, which also contained human factor IX (hFIX) cDNA driven by Rous
      sarcoma virus long terminal repeat in the E1 region, were then constructed and
      expanded in 293 cells permanently expressing GAL4/VP16 fusion protein. Viral
      replication and expression of adenovirus E4 genes and late genes (hexon and
      fiber) were evaluated in vitro in the human lung carcinoma cell line H1299. Viral
      replication and viral gene expression were dramatically reduced in the cells
      transduced by vectors with a replaced E4 promoter compared to the levels in the
      cells transduced by vectors with the wild-type E4 promoter. The levels of
      transgene (hFIX) expression remained similar between vectors with or without E4
      promoter replacement. These results indicate that diminution of viral gene
      expression and viral replication is achievable by promoter replacement.

PMID- 9151875
TI  - Hepatitis B virus replication is cell cycle independent during liver regeneration
      in transgenic mice.
AB  - The content of hepatitis B virus (HBV) replicative forms and HBV core protein in
      the liver of HBV transgenic mice is transiently reduced during massive liver
      regeneration following partial hepatectomy while the steady-state content of
      viral RNA is unchanged. This antiviral effect is triggered by interferon and
      tumor necrosis factor that are induced in the liver following hepatectomy and
      either prevent the formation or accelerate the degradation of viral nucleocapsids
      in the cytoplasm of the hepatocyte. Despite massive hepatocellular turnover, this
      effect is independent of liver cell division, indicating that HBV replicates
      efficiently in resting and dividing hepatocytes.

PMID- 9151876
TI  - Human immunodeficiency virus-associated vasculopathy in transgenic mice.
AB  - There is substantial clinical evidence for the development of vascular disorders
      in human immunodeficiency virus (HIV)-infected individuals, particularly in the
      form of vasculitis. Transgenic mice carrying a replication-defective HIV-1
      provirus with selective deletion of the gag, pol, and env genes developed
      extensive vasculopathy. Restricted expression of HIV nonstructural genes in
      smooth muscle cells was accompanied by the migration and proliferation of these
      cells in blood vessels of all sizes and at different body sites. The frequent
      infiltration observed in the hypertrophic vessel walls occurred predominantly in
      the adventitia and was composed of primarily T cells and occasionally plasma
      cells. The intimal thickening generated significant luminal narrowing in some
      vessels, and the restricted blood flow led to ischemia in the affected tissues.
      Interestingly, the endothelium did not appear to support HIV gene expression or
      be involved in the pathological process. This transgenic model provides an
      opportunity to dissect the mechanism underlying HIV-associated vasculopathy.

PMID- 9151877
TI  - Efficient pseudotyping of murine leukemia virus particles with chimeric human
      foamy virus envelope proteins.
AB  - Incorporation of human foamy virus (HFV) envelope proteins into murine leukemia
      virus (MuLV) particles was studied in a transient transfection packaging cell
      system. We report here that wild-type HFV envelope protein can pseudotype MuLV
      particles, albeit at low efficiency. Complete or partial removal of the HFV
      cytoplasmic tail resulted in an abolishment or reduction of HFV-mediated
      infectivity, implicating a role of the HFV envelope cytoplasmic tail in the
      pseudotyping of MuLV particles. Mutation of the endoplasmic reticulum retention
      signal present in the HFV envelope cytoplasmic tail did not result in a higher
      relative infectivity of pseudotyped retroviral vectors. However, a chimeric
      envelope protein, containing an unprocessed MuLV envelope cytoplasmic domain
      fused to a truncated HFV envelope protein, showed an enhanced HFV specific
      infectivity as a result of an increased incorporation of chimeric envelope
      proteins into MuLV particles.

PMID- 9151878
TI  - Simian foamy virus isolated from an accidentally infected human individual.
AB  - Evidence for natural foamy virus (FV) infections in humans is still lacking.
      However, accidental infections of humans with simian FV have been demonstrated by
      serology and PCR, but all previous attempts to recover infectious virus in such
      cases have failed. Here we describe the isolation of a simian FV from peripheral
      blood mononuclear cells (PBMC) of a healthy animal caretaker, who acquired the
      virus 20 years ago from an African green monkey (AGM) bite. Properties of the
      human isolate such as host range in cell cultures including human PBMC and
      ability to induce neutralizing antibodies in the primate host proved to be
      similar to those of FV obtained from AGM. The genomic sequence of the isolate was
      found to be virtually identical to the proviral sequence present in the host
      lymphocytes and related to AGM isolates but distinct from those of all FV
      isolates handled in the laboratory. For successful virus isolation, it was
      essential to stimulate the host lymphocytes by phytohemagglutinin and interleukin
      2 for 2 weeks prior to cocultivation with permissive cells. In contrast to the
      situation found in FV-infected monkeys, virus isolation from the saliva of the
      animal caretaker was not possible, and no evidence for FV transmission to family
      contacts was obtained. We conclude that, in contrast to active infection in
      monkeys, FV persists in a state of latency following accidental infection of
      humans.

PMID- 9151879
TI  - Gene transfer to human cells using retrovirus vectors produced by a new
      polytropic packaging cell line.
AB  - We report here the construction of a new packaging cell line, called MPAC, that
      packages defective retroviral vectors in viral particles with envelope proteins
      derived from a Moloney mink cell focus-inducing (MCF) polytropic virus. We
      characterized the tropism of MPAC-packaged retroviral vectors and show that some
      human cell lines can be infected with these vectors while others cannot. In
      addition, we show that some human cells fully support MCF virus replication while
      others either partially or fully restrict MCF virus replication.

PMID- 9151880
TI  - Monoclonal antibodies to a 55-kilodalton protein present in duck liver inhibit
      infection of primary duck hepatocytes with duck hepatitis B virus.
AB  - As an approach to identifying hepatocyte receptors for the avian hepadnavirus
      duck hepatitis B virus (DHBV), hybridomas were prepared from mice immunized with
      permissive duck hepatocytes. Monoclonal antibodies (MAbs) were screened for the
      ability to inhibit binding of DHBV particles to primary duck hepatocytes and to
      block infection. We identified two MAbs which partially blocked binding and
      caused marked inhibition of infection of primary duck hepatocytes with DHBV. Lack
      of cross-reactivity with DHBV envelope proteins suggested that inhibition of
      infection was due to specific interaction between the antibodies and a host cell
      surface molecule. Both MAbs immunoprecipitated a 55-kDa protein (p55) expressed
      in duck liver and several other duck tissues. p55 homologs were also identified
      in other birds and mammals. We predict from our data that only a small proportion
      of total cellular p55 molecules are expressed at the surfaces of hepatocytes and
      that p55 is involved in some early step in the infectious pathway.

PMID- 9151881
TI  - Association of ERK2 mitogen-activated protein kinase with human immunodeficiency
      virus particles.
AB  - Here we report the presence of a protein kinase activity associated with human
      immunodeficiency virus type 1 (HIV-1) particles. We observed phosphorylation of
      five major proteins by the endogenous protein kinase activity. Phosphoamino acid
      analysis revealed phosphorylated serine and threonine residues. In addition, we
      observed autophosphorylation of two proteins in the presence of gamma-ATP in an
      in-gel phosphorylation assay. These two proteins are not linked by a disulfide
      bond, suggesting that two different protein kinases are associated with HIV-1
      virions. Our results indicate the presence of ERK2 mitogen-activated protein
      kinase and of a 53,000-molecular-weight protein kinase associated with virions.
      Moreover, the use of different HIV strains derived from T cells and promonocytic
      cells, as well as the use of human T-cell leukemia virus type 1 particles,
      demonstrates that ERK2 is strongly associated with retrovirus particles in a cell
      independent manner. Exogenous substrates, such as histone proteins, and a viral
      substrate, such as Gag protein, are phosphorylated by virus-associated protein
      kinases.

PMID- 9151882
TI  - Bovine herpesvirus 1 glycoprotein B does not productively interact with cell
      surface heparan sulfate in a pseudorabies virion background.
AB  - Attachment to cell surface heparan sulfate proteoglycans is the first step in
      infection by several alphaherpesviruses. This interaction is primarily mediated
      by virion glycoprotein C (gC). In herpes simplex virus, in the absence of the
      nonessential gC, heparan sulfate binding is effected by glycoprotein B. In
      contrast, gC-negative pseudorabies virus (PrV) infects target cells via a heparan
      sulfate-independent mechanism, indicating that PrV virion gB does not
      productively interact with heparan sulfate. To assay whether a heterologous
      alphaherpesvirus gB protein will confer productive heparan sulfate binding on gC
      negative PrV, gC was deleted from an infectious PrV recombinant, PrV-9112C2,
      which expresses bovine herpesvirus 1 (BHV-1) gB instead of PrV gB. Our data show
      that gC-negative PrV-BHV-1 gB recombinant 9112C2-delta gCbeta was not inhibited
      in infection by soluble heparin, in contrast to the gC-positive parental strain.
      Similar results were obtained when wild-type BHV-1 was compared with a gC
      negative BHV-1 mutant. Moreover, infection of cells proficient or deficient in
      heparan sulfate biosynthesis occurred with equal efficiency by PrV-9112C2-delta
      gCbeta, whereas heparan sulfate-positive cells showed an approximately fivefold
      higher plating efficiency than heparan sulfate-negative cells with the parental
      gC-positive virus. In summary, our data show that in a PrV gC-negative virion
      background, BHV-1 gB is not able to mediate infection by productive interaction
      with heparan sulfate, and they indicate the same lack of heparin interaction for
      BHV-1 gB in gC-negative BHV-1.

PMID- 9151883
TI  - Uracil DNA glycosylase specifically interacts with Vpr of both human
      immunodeficiency virus type 1 and simian immunodeficiency virus of sooty
      mangabeys, but binding does not correlate with cell cycle arrest.
AB  - The Vpr protein encoded by human immunodeficiency virus type 1 (HIV-1) is
      important for growth of virus in macrophages and prevents infected cells from
      passing into mitosis (G2 arrest). The cellular target for these functions is not
      known, but Vpr of HIV-1 and the related Vpr from simian immunodeficiency virus of
      sooty mangabeys (SIV(SM)) bind the DNA repair enzyme UNG, while the Vpx protein
      of SIV(SM) does not. Nonetheless, a mutational analysis of Vpr showed that
      binding to UNG is neither necessary nor sufficient for the effect of Vpr on the
      cell cycle.

PMID- 9151884
TI  - Contribution of virion ICAM-1 to human immunodeficiency virus infectivity and
      sensitivity to neutralization.
AB  - Incorporation of the intercellular adhesion molecule ICAM-1 into human
      immunodeficiency virus type 1 (HIV-1) particles increased virus infectivity on
      peripheral blood mononuclear cells (PBMCs) by two- to sevenfold. The degree of
      ICAM-1-mediated enhancement was greater for viruses bearing envelope
      glycoproteins derived from primary HIV-1 isolates than for those bearing envelope
      glycoproteins from laboratory-adapted strains. Treatment of target PBMCs with an
      antibody against LFA-1, a principal ICAM-1 receptor, was able to nullify the ICAM
      1-mediated enhancement. The incorporation of ICAM-1 rendered HIV-1 virions less
      susceptible to neutralization by a monoclonal antibody directed against the viral
      envelope glycoproteins. Surprisingly, an antibody against ICAM-1 completely
      neutralized infection by ICAM-1-containing viruses, reducing the efficiency of
      virus entry by almost 100-fold. Thus, HIV-1 neutralization by an ICAM-1-directed
      antibody involves more than an inhibition of the contribution of ICAM-1 to virus
      entry.

PMID- 9151885
TI  - Novel and frequent mutations of hepatitis B virus coincide with a major
      histocompatibility complex class I-restricted T-cell epitope of the surface
      antigen.
AB  - We examined the full-length hepatitis B virus (HBV) envelope (surface antigen or
      HBV small surface antigen [HBsAg]) sequences of 12 different liver samples from
      10 different hepatoma-containing chronic carriers. Surprisingly, novel and
      frequent mutations occurred predominantly at amino acids 40 and 47 of HBsAg, in
      addition to within a known protective B-cell epitope (so-called group a
      determinant of HBsAg 124-148). Approximately 58% of chronic carriers contain
      mutations at the group a determinant. The mutation frequency at the hotspot
      codons 40 and 47 is approximately 83%, 1 order of magnitude higher than at the
      known polymorphic sites of subtype-specific determinants at codons 122 and 160,
      which is approximately 4%. This new mutational domain is found to coincide with a
      major histocompatibility complex class I-restricted T-cell epitope. The potential
      biological significance of this novel mutation in the immunopathogenesis of HBV
      chronic carriers is discussed.

PMID- 9151887
TI  - The carboxy-terminal two-thirds of the cowpea chlorotic mottle bromovirus capsid
      protein is incapable of virion formation yet supports systemic movement.
AB  - Previous investigations into recombination in cowpea chlorotic mottle bromovirus
      (CCMV) resulted in the recovery of an unusual recombinant virus, 3-57, which
      caused a symptomless infection of cowpeas but formed no detectable virions.
      Sequence analysis of cDNA clones derived from 3-57 determined that mutations near
      the 5' terminus of the capsid protein gene introduced an early translational
      termination codon. Further mutations introduced a new in-frame start codon that
      allowed translation of the 3' two-thirds of the capsid protein gene. Based on the
      mutations observed in 3-57, wild-type CCMV clones were modified to determine if
      the carboxyl two-thirds of the capsid protein functions independently of the
      complete protein in long-distance movement. Analysis of these mutants determined
      that while virion formation is not required for systemic infection, the carboxy
      terminal two-thirds of the capsid protein is both required and sufficient for
      systemic movement of viral RNA. This indicates that the CCMV capsid protein is
      multifunctional, with a distinct long-distance movement function in addition to
      its role in virion formation.

PMID- 9151886
TI  - A homolog of interleukin-10 is encoded by the poxvirus orf virus.
AB  - A gene encoding a polypeptide with homology to interleukin-10 (IL-10) has been
      discovered in the genome of orf virus (OV) strain NZ2, a parapoxvirus that
      infects sheep, goats, and humans. The predicted polypeptide sequence shows high
      levels of amino acid identity to IL-10 of sheep (80%), cattle (75%), humans
      (67%), and mice (64%), as well as IL-10-like proteins of Epstein-Barr virus (63%)
      and equine herpesvirus (67%). The C-terminal region, comprising two-thirds of the
      OV protein, is identical to ovine IL-10, which suggests that this gene has been
      captured from its host sheep during the evolution of OV. The IL-10-like gene is
      transcribed early. Conditioned medium from COS cells transfected with a
      eukaryotic expression vector containing the OV IL-10-like gene showed the same
      biological activity as ovine IL-10 in a murine thymocyte proliferation assay. OV
      IL-10 is likely to be important in immune evasion by OV, since IL-10 is a
      multifunctional cytokine that has inhibitory effects on nonspecific immunity and
      Th1 effector function.

PMID- 9151888
TI  - Transformation by bovine papillomavirus type 1 E6 is independent of
      transcriptional activation by E6.
AB  - We have generated mutants of bovine papillomavirus type 1 E6 (BE6) that are
      defective for transcriptional activation and have analyzed these mutants for
      transformation of contact-inhibited cells and association with the mammalian
      protein E6-AP. These BE6 mutants demonstrate that transformation by BE6 does not
      require transcriptional activation and that association of BE6 with E6-AP is a
      function separable from transcriptional activation by BE6. Association of BE6
      with E6-AP appears to be necessary but not sufficient for transformation by BE6.
      In addition, the mutational analysis of BE6 demonstrates that transactivation,
      transformation, and association with E6-AP all require sequences throughout the
      BE6 gene, indicating that the papillomavirus E6 proteins do not have a simple
      domain structure.

PMID- 9151889
TI  - Molecular mimicry and T cell-mediated autoimmune disease.

PMID- 9151890
TI  - Suppression of herpes simplex virus type 1 (HSV-1)-induced pneumonia in mice by
      inhibition of inducible nitric oxide synthase (iNOS, NOS2).
AB  - Intranasal Herpes simplex virus type 1 (HSV-1) infection of mice caused
      pneumonia. Manifestations of the disease included: histological pneumonitis,
      pulmonary influx of lymphocytes, decreased pulmonary compliance, and decreased
      survival. Immunohistochemical staining demonstrated iNOS induction and the
      nitrotyrosine antigen in the lungs of infected, but not uninfected mice,
      suggesting that nitric oxide contributes to the development of pneumonia. To
      elucidate the role of nitric oxide in the pathogenesis of HSV-1 pneumonia,
      infected mice were treated either with the inhibitor of nitric oxide synthase
      activity, N(G)-monomethyl-L-arginine (L-NMMA), or, as a control, with PBS or D
      NMMA. L-NMMA treatment decreased the histological evidence of pneumonia and
      reduced the bronchoalveolar lavage lymphocyte number to one-quarter of the total
      measured in control-treated mice. L-NMMA treatment significantly improved
      survival and pulmonary compliance of HSV-1-infected mice. Strikingly, the L-NMMA
      mediated suppression of pneumonia occurred despite the presence of a 17-fold
      higher pulmonary viral titer. Taken together, these data demonstrated a
      previously unrecognized role of nitric oxide in HSV-1-induced pneumonia. Of note,
      suppression of pneumonia occurred despite higher pulmonary virus content;
      therefore, our data suggest that HSV-1 pneumonia is due to aspects of the
      inflammatory response rather than to direct viral cytopathic effects.

PMID- 9151891
TI  - Role of different T cell receptors in the development of pre-T cells.
AB  - The development of pre-T cells with productive TCR-beta rearrangements can be
      mediated by each the pre-T cell receptor (pre-TCR), the TCR-alphabeta as well as
      the TCR-gammadelta, albeit by distinct mechanisms. Although the TCR-gammadelta
      affects CD4-8- precursor cells irrespective of their rearrangement status by TCR
      beta mechanisms not involving TCR-beta selection, both the pre-TCR and the TCR
      alphabeta select only cells with productive TCR-beta genes for expansion and
      maturation. The TCR-alphabeta appears to be much less effective than the pre-TCR
      because of the paucity of TCR-alpha proteins in TCR-beta-positive precursors
      since an early expressed transgenic TCR-alphabeta can largely substitute for the
      pre-TCR. Thus, the TCR-alphabeta can assume a role not only in the rescue from
      programmed cell death of CD4+8+ but also of CD4-8- thymocytes. In evolution this
      double function of the TCR-alphabeta may have been responsible for the maturation
      of alphabeta T cells before the advent of the pre-TCR-alpha chain.

PMID- 9151892
TI  - T cell receptor (TCR)-beta gene recombination: dissociation from cell cycle
      regulation and developmental progression during T cell ontogeny.
AB  - T cell lymphopoiesis involves extensive cell division and differentiation; these
      must be balanced by export and programmed cell death to maintain thymic
      homeostasis. Details regarding the nature of these processes, as well as their
      relationships to each other and to the definitive process of T cell receptor
      (TCR) gene recombination, are presently emerging. Two widely held concepts are
      that cell cycle status is inherently and inversely linked to gene recombination
      and that the outcomes of gene recombination regulate developmental progression.
      In this study, we analyze TCR-beta recombination and cell cycle status with
      respect to differentiation during early T cell ontogeny. We find that although
      differentiation, cell cycle fluctuations, and gene recombination are coincident
      during normal T cell development, differentiation and cell cycle status are not
      inherently linked to the recombination process or its products. Rather,
      recombination appears to occur in parallel with these events as part of a
      genetically patterned program of development. We propose that the outcome of gene
      recombination (i.e., TCR expression) may not influence developmental progression
      per se, but instead serves to perpetuate those developing cells that have been
      successful in recombination. The potential consequences of this model for the
      regulation of thymic lymphopoiesis and programmed cell death are discussed.

PMID- 9151893
TI  - Several carcinoembryonic antigens (CD66) serve as receptors for gonococcal
      opacity proteins.
AB  - Neisseria gonorrhoeae (GC) is a human pathogen that adheres to and invades
      genital surfaces. Although pili are required for the initial adherence, the
      interaction of GC with epithelial cells is also promoted by a family of outer
      membrane proteins, the opacity (Opa) proteins such as OpaA protein from strain
      MS11. Studies have demonstrated that the interaction of the OpaA GC with
      epithelial cells involves binding to heparan sulfate attached to syndecan
      receptors. However, other Opa proteins interact with CEA gene family member 1
      (CGM1) or biliary glycoprotein (BGP), members of the CD66 antigen family. In this
      study, we demonstrate that, in addition, the 180-kD carcinoembryonic antigen
      (CEA) is a receptor for Opa proteins. This conclusion was based on the following
      observations. First, transfected HeLa cells expressing CEA (HeLa-CEA) and the CEA
      expressing colon cancer cell line (LS 174T) bound and subsequently engulfed the
      Opa+ bacteria. These interactions were inhibited by anti-CEA antibody, but could
      not be inhibited by addition of heparin. Furthermore, OpaI E. coli directly bound
      purified CEA. We also compared the adherence and invasion by Opa+ bacteria of
      CD66 transfected HeLa cells: HeLa-BGPa, HeLa-CGM6, HeLa-NCA, HeLa-CGM1a, HeLa
      CEA, and HeLa-Neo serving as negative control. Using OpaI as the prototype, the
      relative ability of the transfected HeLa cell lines to support adherence was (CEA
      = BGPa >CGM1a >NCA >>CGM6 = Neo). The ability to mediate invasion of the
      transfectant cells was (CGM1a >CEA >BGPa >NCA >CGM6 = Neo). Among the Opa
      proteins tested, OpaC proved to be bifunctional, able to mediate adherence to
      both syndecan receptors and to CD66 antigens.

PMID- 9151894
TI  - The active site of ICP47, a herpes simplex virus-encoded inhibitor of the major
      histocompatibility complex (MHC)-encoded peptide transporter associated with
      antigen processing (TAP), maps to the NH2-terminal 35 residues.
AB  - The herpes simplex virus (HSV) immediate early protein ICP47 inhibits the
      transporter associated with antigen processing (TAP)-dependent peptide
      translocation. As a consequence, empty major histocompatibility complex (MHC)
      class I molecules are retained in the endoplasmic reticulum and recognition of
      HSV-infected cells by cytotoxic T lymphocytes is abolished. We chemically
      synthesized full-length ICP47 (sICP47) and show that sICP47 inhibits TAP
      dependent peptide translocation in human cells. Its biological activity is
      indistinguishable from that of recombinant ICP47 (rICP47). By using synthetic
      peptides, we mapped the core sequence of ICP47 minimally required for TAP
      inhibition to residues 2-35. This segment is located within the region of the
      molecule conserved between ICP47 from HSV-1 and HSV-2. Through alanine scanning
      substitution we identified three segments within this region that are critical
      for the ability to inhibit TAP function. The interaction of ICP47 with TAP is
      unlikely to mimic precisely that of the transported peptides, as deduced from
      differential labeling of the TAP1 and TAP2 subunits using sICP47 fragments with
      chemical cross-linkers.

PMID- 9151896
TI  - Direct ex vivo analysis of activated, Fas-sensitive autoreactive T cells in human
      autoimmune disease.
AB  - The frequency of clonally expanded and persistent T cells recognizing the
      immunodominant autoantigenic peptide of myelin basic protein (MBP)p85-99 was
      directly measured ex vivo in subjects with typical relapsing remitting multiple
      sclerosis (MS). T cells expressing mRNA transcripts encoding T cell receptor
      (TCR)-alpha and -beta chains found in T cell clones previously isolated from
      these subjects recognizing the MBPp85-99 epitope were examined. In contrast to
      frequencies of 1 in 10(5)-10(6) as measured by limiting dilution analysis,
      estimates of the T cell frequencies expressing MBPp85-99-associated TCR chain
      transcripts were as high as 1 in 300. These high frequencies were confirmed by
      performing PCR on single T cells isolated by flow cytometry. MBPp85-99 TCR
      transcripts were present in IL-2 receptor alpha-positive T cells which were
      induced to undergo Fas-mediated cell death upon antigen stimulation. These data
      demonstrate that at least a subpopulation of patients with MS can have a very
      high frequency of activated autoreactive T cells.

PMID- 9151895
TI  - Chronic tumor necrosis factor alters T cell responses by attenuating T cell
      receptor signaling.
AB  - Repeated injections of adult mice with recombinant murine TNF prolong the
      survival of NZB/W F1 mice, and suppress type I insulin-dependent diabetes
      mellitus (IDDM) in non-obese diabetic (NOD) mice. To determine whether repeated
      TNF injections suppress T cell function in adult mice, we studied the responses
      of influenza hemagglutinin-specific T cells derived from T cell receptor (HNT
      TCR) transgenic mice. Treatment of adult mice with murine TNF for 3 wk suppressed
      a broad range of T cell responses, including proliferation and cytokine
      production. Furthermore, T cell responses of HNT-TCR transgenic mice also
      expressing the human TNF-globin transgene were markedly reduced compared to HNT
      TCR single transgenic littermates, indicating that sustained p55 TNF-R signaling
      is sufficient to suppress T cell function in vivo. Using a model of chronic TNF
      exposure in vitro, we demonstrate that (a) chronic TNF effects are dose and time
      dependent, (b) TNF suppresses the responses of both Th1 and Th2 T helper subsets,
      (c) the suppressive effects of endogenous TNF produced in T cell cultures could
      be reversed with neutralizing monoclonal antibodies to TNF, and (d) prolonged TNF
      exposure attenuates T cell receptor signaling. The finding that anti-TNF
      treatment in vivo enhances T cell proliferative responses and cytokine production
      provides evidence for a novel regulatory effect of TNF on T cells in healthy
      laboratory mice. These effects are more pronounced in chronic inflammatory
      disease. In addition, our data provide a mechanism through which prolonged TNF
      exposure suppresses disease in animal models of autoimmunity.

PMID- 9151897
TI  - Human macrophage-derived chemokine (MDC), a novel chemoattractant for monocytes,
      monocyte-derived dendritic cells, and natural killer cells.
AB  - A cDNA encoding a novel human chemokine was isolated by random sequencing of cDNA
      clones from human monocyte-derived macrophages. This protein has been termed
      macrophage-derived chemokine (MDC) because it appears to be synthesized
      specifically by cells of the macrophage lineage. MDC has the four-cysteine motif
      and other highly conserved residues characteristic of CC chemokines, but it
      shares <35% identity with any of the known chemokines. Recombinant MDC was
      expressed in Chinese hamster ovary cells and purified by heparin-Sepharose
      chromatography. NH2-terminal sequencing and mass spectrophotometry were used to
      verify the NH2 terminus and molecular mass of recombinant MDC (8,081 dalton). In
      microchamber migration assays, monocyte-derived dendritic cells and IL-2
      activated natural killer cells migrated to MDC in a dose-dependent manner, with a
      maximal chemotactic response at 1 ng/ml. Freshly isolated monocytes also migrated
      toward MDC, but with a peak response at 100 ng/ml MDC. Northern analyses
      indicated MDC is highly expressed in macrophages and in monocyte-derived
      dendritic cells, but not in monocytes, natural killer cells, or several cell
      lines of epithelial, endothelial, or fibroblast origin. High expression was also
      detected in normal thymus and less expression in lung and spleen. Unlike most
      other CC chemokines, MDC is encoded on human chromosome 16. MDC is thus a unique
      member of the CC chemokine family that may play a fundamental role in the
      function of dendritic cells, natural killer cells, and monocytes.

PMID- 9151898
TI  - Immediate early and early lytic cycle proteins are frequent targets of the
      Epstein-Barr virus-induced cytotoxic T cell response.
AB  - Epstein-Barr virus (EBV), a human gamma-herpesvirus, can establish both
      nonproductive (latent) and productive (lytic) infections. Although the CD8+
      cytotoxic T lymphocyte (CTL) response to latently infected cells is well
      characterized, very little is known about T cell controls over lytic infection;
      this imbalance in our understanding belies the importance of virus-replicative
      lesions in several aspects of EBV disease pathogenesis. The present work shows
      that the primary CD8+ CTL response to EBV in infectious mononucleosis patients
      contains multiple lytic antigen-specific reactivities at levels at least as high
      as those seen against latent antigens; similar reactivities are also detectable
      in CTL memory. Clonal analysis revealed individual responses to the two immediate
      early proteins BZLF1 and BRLF1, and to three (BMLF1, BMRF1, and BALF2) of the six
      early proteins tested. In several cases, the peptide epitope and HLA-restricting
      determinant recognized by these CTLs has been defined, one unusual feature being
      the number of responses restricted through HLA-C alleles. The work strongly
      suggests that EBV-replicative lesions are subject to direct CTL control in vivo
      and that immediate early and early proteins are frequently the immunodominant
      targets. This contrasts with findings in alpha- and beta-herpesvirus systems
      (herpes simplex, cytomegalovirus) where viral interference with the antigen
      processing pathway during lytic infection renders immediate early and early
      proteins much less immunogenic. The unique capacity of gamma-herpesvirus to
      amplify the viral load in vivo through a latent growth-transforming infection may
      have rendered these agents less dependent upon viral replication as a means of
      successfully colonizing their hosts.

PMID- 9151899
TI  - The cytolytically inactive terminal complement complex activates endothelial
      cells to express adhesion molecules and tissue factor procoagulant activity.
AB  - The membrane attack complex of complement (C) in sublytic concentrations
      stimulates endothelial cells (EC) to express adhesion molecules and to release
      biologically active products. We have examined the ability of a cytolytically
      inactive form of this complex, which is incapable of inserting into the cell
      membrane, to upregulate the expression of adhesion molecules and of tissue factor
      (TF) procoagulant activity. The inactive terminal C complex (iTCC) was prepared
      by mixing C5b6, C7, C8, and C9 and was purified by fast protein liquid
      chromatography on a Superose 12 column. Binding of this complex to EC was found
      to be dose dependent and was inhibited by anti-C9 antibodies, as assessed both by
      ELISA using an mAb anti-C9 neoantigen and by measuring cell-bound 125I-labeled
      iTCC. Exposure of EC to iTCC resulted in a dose- and time-dependent expression of
      endothelial leukocyte adhesion molecule 1, intercellular adhesion molecule 1, and
      vascular cell adhesion molecule 1 accompanied by increased levels of the
      corresponding mRNA, but not in the rapid expression of P-selectin. Inactive TCC
      also induced increased TF activity evaluated by a chromogenic assay that measures
      the formation of factor Xa. These effects were inhibited by anti-C9 antibodies.
      The data support the conclusion that iTCC may induce proinflammatory and
      procoagulant activities on EC.

PMID- 9151900
TI  - Minimal bystander activation of CD8 T cells during the virus-induced polyclonal T
      cell response.
AB  - Acute infections with viruses such as lymphocytic choriomeningitis virus (LCMV)
      are associated with a massive polyclonal T cell response, but the specificities
      of only a small percentage of these activated T cells are known. To determine if
      bystander stimulation of T cells not specific to the virus plays a role in this T
      cell response, we examined two different systems, HY-specific T cell receptor
      (TCR)-transgenic mice, which have a restricted TCR repertoire, and LCMV-carrier
      mice, which are tolerant to LCMV. LCMV infection of HY-transgenic C57BL/6 mice
      induced antiviral CTLs that lysed target cells coated with two of the three
      immunodominant epitopes previously defined for LCMV (glycoprotein 33 and
      nucleoprotein 397). Although LCMV-induced cytotoxic T lymphocytes (CTLs) from
      C57BL/6 mice could lyse uninfected H-2(k) and H-2(d) allogeneic targets, LCMV
      induced CTLs from HY mice lysed only the H-2(k)-expressing cells. The HY mice
      generated both anti-H-2(k) and anti-H-2(d) CTL in mixed leukocyte reactions,
      providing evidence that the generation of allospecific CTLs during acute LCMV
      infection is antigen specific. During the LCMV infection there was blastogenesis
      of the CD8+ T cell population, but the HY-specific T cells (as determined by
      expression of the TCR-alpha chain) remained small in size. To examine the
      potential for bystander stimulation under conditions of a very strong CTL
      response, T cell chimeras were made between normal and HY mice. Even in the
      context of a normal virus-induced CTL response, no stimulation of HY-specific T
      cells was observed, and HY-specific cells were diluted in number by day 9 after
      infection. In LCMV-carrier mice in which donor and host T cells could be
      distinguished by Thy1 allotypic markers, adoptive transfer of LCMV-immune T cells
      into LCMV-carrier mice, whose T cells were tolerant to LCMV, resulted in
      activation and proliferation of donor CD8 cells, but little or no activation of
      host CD8 cells. These results support the hypothesis that the massive polyclonal
      CTL response to LCMV infection is virus-specific and that bystander activation of
      non-virus-specific T cells is not a significant component of this response.

PMID- 9151901
TI  - Pathogenesis of an infectious mononucleosis-like disease induced by a murine
      gamma-herpesvirus: role for a viral superantigen?
AB  - The murine gamma-herpesvirus 68 has many similarities to EBV, and induces a
      syndrome comparable to infectious mononucleosis (IM). The frequency of activated
      CD8+ T cells (CD62L(lo)) in the peripheral blood increased greater than fourfold
      by 21 d after infection of C57BL/6J (H-2(b)) mice, and remained high for at least
      a further month. The spectrum of T cell receptor usage was greatly skewed, with
      as many as 75% of the CD8+ T cells in the blood expressing a Vbeta4+ phenotype.
      Interestingly, the Vbeta4 dominance was also seen, to varying extents, in H-2(k),
      H-2(d), H-2(u), and H-2(q) strains of mice. In addition, although CD4 depletion
      from day 11 had no effect on the Vbeta4 bias of the T cells, the Vbeta4+CD8+
      expansion was absent in H-2IA(b)-deficient congenic mice. However, the numbers of
      cycling cells in the CD4 antibody-depleted mice and mice that are CD4 deficient
      as a consequence of the deletion of MHC class II, were generally lower. The
      findings suggest that the IM-like disease is driven both by cytokines provided by
      CD4+ T cells and by a viral superantigen presented by MHC class II glycoproteins
      to Vbeta4+CD8+ T cells.

PMID- 9151902
TI  - Identification of high potency microbial and self ligands for a human
      autoreactive class II-restricted T cell clone.
AB  - CD4+ class II-restricted T cells specific for self antigens are thought to be
      involved in the pathogenesis of most human autoimmune diseases and molecular
      mimicry between foreign and self ligands has been implicated as a possible
      mechanism for their activation. In this report we introduce combinatorial peptide
      libraries as a powerful tool to identify cross-reactive ligands for these T
      cells. The antigen recognition of a CD4+ T cell clone (TCC) specific for myelin
      basic protein peptide (MBP) (86-96) was dissected by the response to a set of 220
      11-mer peptide sublibraries. Based on the results obtained with the libraries for
      each position of the antigen, artificial peptides were found that induced
      proliferative responses at much lower concentrations than MBP(86-96). In addition
      stimulatory ligands derived from protein sequences of self and microbial proteins
      were identified, some of them even more potent agonists than MBP(86-96). These
      results indicate that: (a) for at least some autoreactive CD4+ T cells antigen
      recognition is highly degenerate; (b) the autoantigen used to establish the TCC
      represents only a suboptimal ligand for the TCC; (c) a completely random and
      unbiased approach such as combinatorial peptide libraries can decrypt the
      spectrum of stimulatory ligands for a T cell receptor (TCR).

PMID- 9151903
TI  - Lipopolysaccharide (LPS)-induced macrophage activation and signal transduction in
      the absence of Src-family kinases Hck, Fgr, and Lyn.
AB  - Lipopolysaccharide (LPS) stimulates immune responses by interacting with the
      membrane receptor CD14 to induce the generation of cytokines such as tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-1, and IL-6. The mechanism by which
      the LPS signal is transduced from the extracellular environment to the nuclear
      compartment is not well defined. Recently, an increasing amount of evidence
      suggests that protein tyrosine kinases especially the Src-family kinases Hck,
      Fgr, and Lyn, play important roles in LPS signaling. To directly address the
      physiological function of Hck, Fgr and Lyn in LPS signaling, a genetic approach
      has been used to generate null mutations of all three kinases in a single mouse
      strain. hck-/-fgr-/-lyn-/- mice are moderately healthy and fertile; macrophages
      cultured from these mice express normal levels of CD14 and no other Src-family
      kinases were detected. Although the total protein phosphotyrosine level is
      greatly reduced in macrophages derived from hck-/-fgr-/-lyn-/- mice, functional
      analyses indicate that both elicited peritoneal (PEMs) and bone marrow-derived
      macrophages (BMDMs) from triple mutant mice have no major defects in LPS-induced
      activation. Nitrite production and cytokine secretion (IL-1, IL-6, and TNF-alpha)
      are normal or even enhanced in hck-/-fgr-/-lyn-/- macrophages after LPS
      stimulation. The development of tumor cell cytotoxicity is normal in triple
      mutant BMDMs and only partially impaired in PEMs after LPS stimulation.
      Furthermore, the activation of the ERK1/2 and JNK kinases, as well as the
      transcription factor NF-kappaB, are the same in normal and mutant macrophages
      after LPS stimulation. The current study provides direct evidence that three Src
      family kinases Hck, Fgr, and Lyn are not obligatory for LPS-initiated signal
      transduction.

PMID- 9151904
TI  - Costimulation through B7-2 (CD86) is required for the induction of a lung mucosal
      T helper cell 2 (TH2) immune response and altered airway responsiveness.
AB  - The recruitment of eosinophils into the airways after allergen exposure is
      dependent on interleukin (IL) 5 secreted from antigen-specific CD4+ T cells of
      the T helper cell (Th) 2 subset. However, while it is established that
      costimulation through CD28 is required for TCR-mediated activation and IL-2
      production, the importance of this mechanism for the induction of a Th2 immune
      response is less clear. In the present study, we administered the fusion protein
      CTLA-4 immunoglobulin (Ig) into the lungs before allergen provocation to
      determine whether CD28/CTLA-4 ligands are required for allergen-induced
      eosinophil accumulation and the production of Th2 cytokines. Administration of
      CTLA-4 Ig inhibited the recruitment of eosinophils into the lungs by 75% and
      suppressed IgE in the bronchoalveolar lavage fluid. CTLA-4 Ig also inhibited the
      production of IL-4, IL-5, and IL-10 by 70-80% and enhanced interferon-gamma
      production from CD3-T cell receptor-activated lung Thy1.2+ cells. Allergen
      exposure upregulated expression of B7-2, but not B7-1, on B cells from the lung
      within 24 h. Moreover, airway administration of an anti-B7-2 monoclonal antibody
      (mAb) inhibited eosinophil infiltration, IgE production, and Th2 cytokine
      secretion comparable in magnitude to that observed with CTLA-4 Ig. Treatment with
      an anti-B7-1 mAb had a small, but significant effect on eosinophil accumulation,
      although was less effective in inhibiting Th2 cytokine production. The anti-B7-2,
      but not anti-B7-1, mAb also inhibited antigen-induced airway hyperresponsiveness
      in vivo. In all of the parameters assessed, the combination of both the anti-B7-1
      and anti-B7-2 mAb was no more effective than anti-B7-2 mAb treatment alone. We
      propose that strategies aimed at inhibition of CD28 interactions with B7-2
      molecules may represent a novel therapeutic target for the treatment of lung
      mucosal allergic inflammation.

PMID- 9151906
TI  - Aspirin-triggered 15-epi-lipoxin A4 (LXA4) and LXA4 stable analogues are potent
      inhibitors of acute inflammation: evidence for anti-inflammatory receptors.
AB  - Lipoxins are bioactive eicosanoids that are immunomodulators. In human myeloid
      cells, lipoxin (LX) A4 actions are mediated by interaction with a G protein
      coupled receptor. To explore functions of LXA4 and aspirin-triggered
      5(S),6(R),15(R)-trihydroxy-7,9,13-trans-11-cis-eicosatetraenoic acid (15-epi
      LXA4) in vivo, we cloned and characterized a mouse LXA4 receptor (LXA4R). When
      expressed in Chinese hamster ovary cells, the mouse LXA4R showed specific binding
      to [3H]LXA4 (K(d) approximately 1.5 nM), and with LXA4 activated GTP hydrolysis.
      Mouse LXA4R mRNA was most abundant in neutrophils. In addition to LXA4 and 15-epi
      LXA4, bioactive LX stable analogues competed with both [3H]LXA4 and
      [3H]leukotriene D4 (LTD4)-specific binding in vitro to neutrophils and
      endothelial cells, respectively. Topical application of LXA4 analogues and novel
      aspirin-triggered 15-epi-LXA4 stable analogues to mouse ears markedly inhibited
      neutrophil infiltration in vivo as assessed by both light microscopy and reduced
      myeloperoxidase activity in skin biopsies. The 15(R)-16-phenoxy-17,18, 19,20
      tetranor-LXA4 methyl ester (15-epi-16-phenoxy-LXA4), an analogue of aspirin
      triggered 15-epi-LXA4, and 15(S)-16-phenoxy-17,18,19,20-tetranor-LXA4 methyl
      ester (16-phenoxy-LXA4) were each as potent as equimolar applications of the anti
      inflammatory, dexamethasone. Thus, we identified murine LXA4R, which is highly
      expressed on murine neutrophils, and showed that both LXA4 and 15-epi-LXA4 stable
      analogues inhibit neutrophil infiltration in the mouse ear model of inflammation.
      These findings provide direct in vivo evidence for an anti-inflammatory action
      for both aspirin-triggered LXA4 and LXA4 stable analogues and their site of
      action in vivo.

PMID- 9151907
TI  - Resistance to Leishmania major is linked to the H2 region on chromosome 17 and to
      chromosome 9.
AB  - In Leishmaniasis, as in many infectious diseases, clinical manifestations are
      determined by the interaction between the genetics of the host and of the
      parasite. Here we describe studies mapping two loci controlling resistance to
      murine cutaneous leishmaniasis. Mice infected with L. major show marked genetic
      differences in disease manifestations: BALB/c mice are susceptible, exhibiting
      enlarging lesions that progress to systemic disease and death, whereas C57BL/6
      are resistant, developing small, self-healing lesions. F2 animals from a C57BL/6
      X BALB/c cross showed a continuous distribution of lesion score. Quantitative
      trait loci (QTL) have been mapped after a non-parametric QTL analysis on a genome
      wide scan on 199 animals. QTLs identified were confirmed in a second cross of 271
      animals. Linkage was confirmed to a chromosome 9 locus (D9Mit67-D9Mit71) and to a
      region including the H2 locus on chromosome 17. These have been named Imr2 and
      Imr1, respectively.

PMID- 9151909
TI  - Results of 90 consecutive hepatectomies for hepatocellular carcinoma: a
      multivariate analysis of survival.
AB  - The surgical results and postoperative management of 90 patients with
      hepatocellular carcinoma (HCC) who underwent hepatectomy were reviewed, and
      clinical factors relating to HCC were analyzed to determine what type of HCC
      responds best to hepatectomy. The patients consisted of 69 men and 21 women.
      Serum anti-hepatitis C virus was positive in 76.9% of patients and hepatitis B
      surface antigen was positive in 18.9%. The operative procedures consisted of
      right lobectomy in six patients, left lobectomy in seven, right hepatic
      segmentectomy in eight, left lateral segmentectomy in 13, two adjoining
      subsegmentectomy in 17, subsegmentectomy in 29, and partial hepatectomy in 10.
      Liver cirrhosis was confirmed histopathologically in 63 patients. There were two
      operative deaths and two other in-hospital deaths. During the follow-up period,
      HCC recurred in 64 of the remaining 86 patients at the following sites: liver in
      56 patients (87.5%), bones in four (6.3%), lymph nodes in three (4.7%), and lung
      in one (1.6%). Transcatheter arterial chemoembolization was performed in 22 of
      the patients with recurrence, transcatheter arterial chemoembolization in
      combination with percutaneous ethanol injection was performed in 14, hepatectomy
      was performed in six, and irradiation with Linac x-rays was performed in eight.
      The cumulative 3- and 5-year survival rates were 63.8% and 37.8%, respectively.
      Univariate and multivariate analyses of factors influencing survival disclosed
      that having a single HCC nodule of up to a maximal diameter of 4.0 cm, an absence
      of intrahepatic metastasis, and a functional liver reserve estimated as clinical
      stage I contributed significantly and independently to increasing the survival
      rate.

PMID- 9151908
TI  - Local delivery of interleukin 4 by retrovirus-transduced T lymphocytes
      ameliorates experimental autoimmune encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an inflammatory autoimmune
      disease of the central nervous system which serves as a model for the human
      disease multiple sclerosis. We demonstrate here that encephalitogenic T cells,
      transduced with a retroviral gene, construct to express interleukin 4, and can
      delay the onset and reduce the severity of EAE when adoptively transferred to
      myelin basic protein-immunized mice. Thus, T lymphocytes transduced with
      retroviral vectors can deliver "regulatory cytokines" in a site-specific manner
      and may represent a viable therapeutic strategy for the treatment of autoimmune
      disease.

PMID- 9151905
TI  - CCR5 levels and expression pattern correlate with infectability by macrophage
      tropic HIV-1, in vitro.
AB  - Chemokine receptors serve as coreceptors for HIV entry into CD4+ cells. Their
      expression is thought to determine the tropism of viral strains for different
      cell types, and also to influence susceptibility to infection and rates of
      disease progression. Of the chemokine receptors, CCR5 is the most important for
      viral transmission, since CCR5 is the principal receptor for primary, macrophage
      tropic viruses, and individuals homozygous for a defective CCR5 allele
      (delta32/delta32) are highly resistant to infection with HIV-1. In this study,
      CCR5-specific mAbs were generated using transfectants expressing high levels of
      CCR5. The specificity of these mAbs was confirmed using a broad panel of
      chemokine receptor transfectants, and by their non-reactivity with T cells from
      delta32/delta32 individuals. CCR5 showed a distinct pattern of expression, being
      abundant on long-term activated, IL-2-stimulated T cells, on a subset of
      effector/memory T cells in blood, and on tissue macrophages. A comparison of
      normal and CCR5 delta32 heterozygotes revealed markedly reduced expression of
      CCR5 on T cells from the heterozygotes. There was considerable individual to
      individual variability in the expression of CCR5 on blood T cells, that related
      to factors other than CCR5 genotype. Low expression of CCR5 correlated with the
      reduced infectability of T cells with macrophage-tropic HIV-1, in vitro. Anti
      CCR5 mAbs inhibited the infection of PBMC by macrophage-tropic HIV-1 in vitro,
      but did not inhibit infection by T cell-tropic virus. Anti-CCR5 mAbs were poor
      inhibitors of chemokine binding, indicating that HIV-1 and ligands bind to
      separate, but overlapping regions of CCR5. These results illustrate many of the
      important biological features of CCR5, and demonstrate the feasibility of
      blocking macrophage-tropic HIV-1 entry into cells with an anti-CCR5 reagent.

PMID- 9151911
TI  - Serum transforming growth factor-alpha level can be a parameter for evaluating
      liver regeneration after partial hepatectomy in patients with liver cancer.
AB  - Sensitive and reliable laboratory parameters are necessary to evaluate the degree
      of liver regeneration serially in patients after partial hepatectomy for liver
      cancer. We evaluated the serum levels of transforming growth factor-alpha (TGF
      alpha) and hepatocyte growth factor (HGF), both of which are potent mitogens for
      hepatocytes, in 22 hepatectomized patients with liver cancer: 10 patients with
      hepatocellular carcinoma and 12 patients with metastatic liver tumors. Ten
      patients who underwent laparotomy for nonhepatic surgery were also studied as
      surgical controls. The serum TGF-alpha and HGF levels were measured by sandwich
      enzyme-linked immunosorbent assay techniques. Both the serum TGF-alpha and HGF
      levels increased after partial hepatectomy. However, there was no correlation
      between the levels of TGF-alpha and HGF. The maximal level of TGF-alpha achieved
      in each case correlated significantly with the resected liver volume and the
      increased volume of the remaining liver. Hepatocyte growth factor showed no such
      correlations. After nonhepatic surgery, the HGF level also increased
      significantly, while the TGF-alpha level did not. These results suggest that the
      serum TGF-alpha level varies depending on the regenerative stimulus to the liver,
      and that its increase corresponds with the degree of liver regeneration that
      occurs in patients after partial hepatectomy for liver cancer. In contrast, it is
      unlikely that the serum HGF level reflects liver regeneration. In conclusion, the
      serum TGF-alpha level can be used as a parameter for evaluating liver
      regeneration in patients who have undergone partial hepatectomy.

PMID- 9151910
TI  - Clinicopathologic factors influencing the long-term prognosis following hepatic
      resection for large hepatocellular carcinoma more than 10 cm in diameter.
AB  - We resected 158 cases of hepatocellular carcinoma (HCC), including 20 (12.6%)
      cases of large HCC. These 20 cases were divided into group 1 (curative resection,
      n = 9) and group 2 (noncurative resection, n = 11). The clinicopathologic
      features and long-term survival of the cases were evaluated. In groups 1 and 2,
      portal vein invasion (Vp+) was noted in 44.4% and 63.3%, intrahepatic metastasis
      (IM+) in 77.8% and 100%, absence of a fibrous capsule (Fc-) in 55.6% and 63.6%,
      and stage III or IV in 77.8% and 100%, respectively. The DNA ploidy pattern was
      aneuploid in 44.4% of group 1 and 100% of group 2. In group 1, the 1-, 3-, and 5
      year cumulative survival rates were 75%, 62.5%, and 62.5%, respectively (the
      longest survivor is alive after 11 years 1 month). Five cases survived more than
      3 years in group 1, and all were Vp(-) and nonaneuploid. On the other hand, in
      group 2, the 1-year survival rate was only 33.3%; none survived more than 2
      years. These results suggest that even patients with large HCC have a favorable
      long-term prognosis if their clinicopathologic factors are Vp(-) and
      nonaneuploid, and if curative resection can be performed.

PMID- 9151912
TI  - Adjuvant chemotherapy with epirubicin and carmofur after radical resection of
      hepatocellular carcinoma: a prospective randomized study.
AB  - The intrahepatic recurrence rate is extremely high, even after radical resection
      of hepatocellular carcinoma (HCC). One report showed intra-arterial
      administration of epirubicin to be effective in the treatment of nonresectable
      HCC. We evaluated the effect of postoperative adjuvant chemotherapy including
      this drug. Fifty-seven patients who had undergone radical resection of HCC were
      entered in this study. Using the sealed-envelope method, 27 patients were
      assigned to a group undergoing resection only and 29 patients to a group also
      receiving adjuvant chemotherapy after resection. The protocol of the chemotherapy
      was intra-arterial administration of epirubicin (40 mg/m2) at 1 month after
      resection followed by intravenous administration of epirubicin (40 mg/m2) every 3
      months for 2 years. In addition, 1-hexylcarbamoyl-5-fluorouracil (HCFU;
      carmofur), 300 mg/d, was administered orally every day, beginning from 1 month
      after the resection and continuing (in principle) for 24 months. The
      clinicopathologic backgrounds were well randomized between the two groups. The
      chemotherapy protocol was performed completely in only five patients (7.2%).
      Twenty-four (82.8%) patients had to cease the protocol due to various reasons:
      change to a new therapy after recurrence of HCC in 19 cases (79.2%), severe side
      effects of the chemotherapy in three cases (12.5%), liver failure in one case
      (4.2%), and a postoperative complication in one case (4.2%). The mean total doses
      were 128 +/- 114 mg for epirubicin and 144 +/- 84 g for HCFU. The cumulative
      overall and disease-free survival rates for 5 years were not significantly
      different between the two groups. The results of this prospective randomized
      study suggest that this adjuvant chemotherapy protocol with epirubicin and HCFU
      after radical resection of HCC was not effective.

PMID- 9151913
TI  - Hepatocellular carcinoma patients showing long-term complete responses to
      chemoembolization.
AB  - The objective was to evaluate hepatocellular carcinoma (HCC) patients showing a
      long-term complete response (CR) to chemoembolization. We defined the criteria of
      CR as normalized tumor marker, no enhanced tumor in diagnostic images, and no
      tumor cells found at autopsy. Five HCC patients showing long-term CR to
      chemoembolization were evaluated. The CR period ranged from 3.5 to 7 years (mean,
      5.7 years). The survival period ranged from 3.5 to 9 years (mean, 6.7 years).
      Four cases (80%) were stage IV according to the TNM classification due to a
      portal tumor thrombus. The liver function was rated as Child's A in four cases
      (80%). Long-term CR to chemoembolization can be achieved even in some advanced
      HCC cases with a tumor thrombus. We speculate that the good antitumor effect is
      brought about by the stagnation of both the arterial and portal blood flows to
      the HCC. Good liver function is also considered to be an important factor for
      long-term CR and a long survival period. If the liver function is good, advanced
      HCC with a portal tumor thrombus should be treated aggressively with
      chemoembolization.

PMID- 9151914
TI  - Factors associated with survival exceeding 5 years after transcatheter arterial
      embolization for hepatocellular carcinoma.
AB  - During the period between April 1981 and March 1988, 232 consecutive patients
      underwent transcatheter arterial embolization (TAE) for hepatocellular carcinoma
      at the Department of Radiology, Wakayama Medical College. A > or = 5-year course
      calculated from the time of the initial TAE was able to be confirmed in 216
      patients, who became the subjects of this study. Five-year survival rates were
      calculated by the direct method, while the clinical features existing at the time
      of the initial therapy and the clinical course of patients surviving > or = 5
      years were studied. The 5-year survival rate was 6.0%. Comparison of the patients
      dying within 1 year and the patients surviving for > or = 5 years revealed
      differences in the severity of liver cirrhosis and the tumor type. The long-term
      survivors tended to have low serum alpha-fetoprotein values. The clinical picture
      of the patients surviving > or = 5 years after TAE was characterized by
      relatively mild liver cirrhosis (Child's class A or B), a serum alpha-fetoprotein
      value of < or = 1,500 ng/dL, relatively small nodular-type tumors with a maximum
      main tumor diameter of < or = 5.5 cm, a tumor-occupying rate of less than 20%,
      and absence of portal vein involvement by the tumor. There were patients in whom
      a relatively small number of TAE sessions was effective in controlling the tumor
      for a prolonged period, with the patients then dying of causes unrelated to the
      tumor, as well as patients in whom proliferation of the tumor was controlled by
      numerous applications of transcatheter therapy, resulting in > or = 5-year
      survival but with eventual death due to the tumor. Transcatheter arterial
      embolization makes a major contribution to achieving long-term survival of > or =
      5 years in patients with hepatocellular carcinoma.

PMID- 9151915
TI  - Prospective and randomized trial of lipiodol-transcatheter arterial
      chemoembolization for treatment of hepatocellular carcinoma: a comparison of
      epirubicin and doxorubicin (second cooperative study). The Cooperative Study
      Group for Liver Cancer Treatment of Japan.
AB  - A randomized, controlled clinical trial was conducted to compare the use of
      epirubicin (EPI) and doxorubicin (DOX) in Lipiodol (Laboratoire Guerbet, Roissy
      Charles-de-Gaulle Cedex, France)-transcatheter arterial chemoembolization as a
      treatment of hepatocellular carcinoma. One hundred ninety-two hospitals
      participated, and 415 patients were enrolled in the study during the period
      between October 1989 and December 1990. The patients were randomly allocated to
      group A (EPI) or group B (DOX) by a centralized telephone registration. The
      actual doses of EPI and DOX were 72 mg/body and 48 mg/body, respectively. The 1-,
      2-, and 3-year survival rates were, respectively, 69%, 44%, and 33% for group A
      and 73%, 54%, and 37% for group B. There were no statistically significant
      differences (P = .2296, log-rank test). When each group of patients was
      classified retrospectively into high-risk and low-risk subgroups based on the
      severity index calculated by the Cox regression model from the significant
      prognostic factors (the pretreatment tumor size, the pretreatment serum alpha
      fetoprotein level, tumor encroachment, and Child's classification), the survival
      curve of the low-risk DOX subgroup was significantly superior to that of the low
      risk EPI subgroup (P = .0182). However, there was no significant difference
      between the high-risk subgroups (P = .4606). The change in the serum alpha
      fetoprotein level, the extent of Lipiodol accumulation in the tumor, and the
      extent of tumor reduction after the treatment did not show any significant
      differences between the groups. The white blood cell count in group B showed a
      tendency to decrease slightly more than in group A at 3 weeks after Lipiodol
      transcatheter arterial chemoembolization. In conclusion, there was no
      statistically significant difference between the survival curves of the EPI and
      DOX groups in Lipiodol-transcatheter arterial embolization treatment of
      hepatocellular carcinoma.

PMID- 9151916
TI  - Combination of transcatheter arterial embolization and percutaneous ethanol
      injection for hepatocellular carcinoma: comparison of efficacies of doxorubicin
      and epirubicin in transcatheter arterial embolization.
AB  - We administered a combination of transcatheter arterial embolization (TAE) and
      percutaneous ethanol injection (PEI) (ie, pretreatment with TAE and subsequent
      PEI) to treat 56 patients with multiple lesions (number of nodules < or = 3) or a
      single large (diameter > or = 3 cm) encapsulated lesion of hepatocellular
      carcinoma. The TAE included doxorubicin (40 mg) in 32 cases and epirubicin (mean,
      82 mg) in the remaining 24 cases, and the efficacies of the two were compared.
      The therapeutic efficacy was evaluated on the basis of the survival rate and
      recurrence-free survival rate revealed by clinical follow-up. Both rates showed
      significant differences between the doxorubicin and epirubicin groups, with both
      being superior in the epirubicin group. It was surmised that epirubicin is a
      useful chemotherapeutic agent in TAE for patients with hepatocellular carcinoma.

PMID- 9151918
TI  - Antitumor effect of transcatheter oily chemoembolization for hepatocellular
      carcinoma assessed by computed tomography: role of iodized oil.
AB  - The efficacy of transcatheter oily chemoembolization (TOCE) was evaluated in 82
      patients with unresectable hepatocellular carcinoma (HCC) by computed tomography
      more than 6 months after TOCE. A doxorubicin in oil emulsion (DOE) was
      administered to 42 cases and an epirubicin in oil emulsion (EOE) was administered
      to 40 cases. No significant differences were found in the patient background
      characteristics between the DOE-treated group and the EOE-treated group. Tumor
      regression of more than 50% of the product of two dimensions was observed in 26
      DOE-treated cases and in 25 EOE-treated cases at 1 year or more after TOCE. No
      difference in antitumor effect was observed between DOE and EOE, although a
      sufficient dose per tumor volume would be required to manifest an antitumor
      effect on hepatocellular carcinoma.

PMID- 9151917
TI  - Evaluation of combined therapy with chemoembolization and ethanol injection for
      advanced hepatocellular carcinoma.
AB  - To evaluate the therapeutic efficacy of transcatheter arterial chemoembolization
      (TACE) combined with percutaneous ethanol injection therapy (PEIT) for advanced
      hepatocellular carcinoma, we studied the effectiveness of TACE therapy combined
      with PEIT (50 cases) and TACE alone (50 cases). In both groups, patients had
      multiple lesions, or a single lesion with a diameter exceeding 2 cm or with
      vascular invasion (stages II, III, and IV in the tumor staging classification of
      the Liver Cancer Study Group of Japan). The clinical features in the two groups
      were comparable. The cumulative survival rates with TACE-PEIT were 95.0% for 1
      year, 72.5% for 2 years, and 50.0% for 3 years, whereas the rates with TACE alone
      were 92.5% for 1 year, 57.5% for 2 years, and 20.0% for 3 years. The survival
      rate in the TACE-PEIT group was significantly higher than that in the TACE alone
      group. Moreover, the survival rate of patients with stage II or III disease in
      the TACE-PEIT group was significantly better than that in the TACE alone group,
      and the survival rate of patients with Child's classification B or C in the TACE
      PEIT group was significantly higher than that in the TACE alone group.
      Multivariate analysis using Cox's proportional hazard regression model showed
      that the most significant prognostic factors in the TACE-PEIT group were tumor
      embolus in the portal vein and the number of tumors. These results suggest the
      effectiveness of combining TACE and PEIT for the treatment of advanced
      hepatocellular carcinoma.

PMID- 9151919
TI  - Optimal lipiodol volume in transcatheter arterial chemoembolotherapy for
      hepatocellular carcinoma: study based on lipiodol accumulation patterns and
      histopathologic findings.
AB  - To clarify the optimal dose of Lipiodol (Andre Guerbet, Aulnay-sous-Bois, France)
      during Lipiodol-transcatheter arterial embolization (L-TAE) and segmental L-TAE
      used to treat hepatocellular carcinoma, we studied the relationship between the
      volume of Lipiodol used during these procedures and the necrosis rates in
      resected specimens, as well as the correlation with the Lipiodol accumulation
      pattern based on the computed tomography findings (L-CT) and the volume of
      Lipiodol in resected and nonresected cases after L-TAE or segmental L-TAE. The L
      CT and the dose of Lipiodol injected (mL) were studied correlatively in 198 cases
      (28 resected cases and 170 nonresected cases; tumor size < or = 5 cm in 52 cases
      and > 5 cm in 118 cases) that underwent L-TAE and in 80 cases (14 resected cases
      and 66 nonresected cases, tumor size < or = 5 cm in 52 cases and > 5 cm in 14
      cases) that underwent segmental L-TAE. The L-CT was classified into four types:
      type I, homogeneous accumulation (type Ia, accumulation around the tumor; type
      Ib, no accumulation around the tumor); type II, partial defect; type III,
      sporadic accumulation; and type IV, punctate or no accumulation. In the 42
      resected cases (L-TAE, 28 cases; segmental L-TAE, 14 cases), type I was seen in
      68% (Ib, 100%) of the L-TAE cases and 93% (Ia, 79%; Ib, 14%) of the segmental L
      TAE cases. The necrosis rate of the cases with type Ib L-CT was 90% to 100%, and
      all type Ia cases showed complete necrosis. In the 236 nonresected cases (L-TAE,
      170 cases; segmental L-TAE, 66 cases), the volume of Lipiodol injected correlated
      with the L-CT type. In the L-TAE cases with a tumor size < or =5 cm, the
      frequency of the injected Lipiodol volume (D) being greater than the tumor
      diameter (d) (D > or = d) was 90%, and 87% of the cases with D > or = d showed
      type Ib L-CT. In the group whose tumor diameter (d) was more than 5 cm, the
      frequency of D > or = d was 25%, and 70% of the cases of D > or = d were type Ib.
      The frequency of D < d was 75%, and in 13% of these cases the L-CT was type Ib
      and the maximum dose was approximately 10 mL. In segmental L-TAE using the same
      dose of Lipiodol as in L-TAE, the frequency of D > or = d was 83%, and 93% of
      those cases showed type I, including 85% of type Ia. There was a correlation
      between the L-CT type and the necrosis rate, and type I, especially Ia in
      segmental L-TAE, showed complete necrosis in almost all cases. In L-TAE,
      standards for the optimal dose of Lipiodol are thought to be as follows: D > or =
      d in cases with d < or = 5, and slightly D < d and 10 mL maximally in cases with
      d > 5. In segmental L-TAE using the same dose of Lipiodol as in L-TAE,
      enhancement of the therapeutic effect was seen compared with L-TAE. This is
      surmised to have been because of the higher Lipiodol volume with anticancer
      agents per unit volume of the tumor in segmental L-TAE.

PMID- 9151920
TI  - Total necrosis of hepatocellular carcinoma with a combination therapy of arterial
      infusion of chemotherapeutic lipiodol and transcatheter arterial embolization:
      report of 14 cases.
AB  - Combination therapy consisting of Lipiodol (Laboratoire Guerbet, Villepinte,
      France) containing styrene maleic acid neocarzinostatin and transcatheter
      arterial embolization (L-TAE) has been an important conservative therapy for
      hepatocellular carcinoma (HCC). We examined the clinical and pathologic
      characteristics of 14 HCC cases that achieved total tumor necrosis in response to
      L-TAE. The HCCs of all cases were resected 45 +/- 17 days after L-TAE and were
      confirmed to be totally necrotic. Ultrasonography showed a mean tumor size of 2.5
      +/- 1.0 cm, often with a halo formation around the tumor. Angiographically,
      neovascularity and clear tumor stains were observed in all cases. Computed
      tomography portography showed nodular perfusion defects in all the cases
      examined. There were portal invasions in two cases. On Lipiodol-computed
      tomography, Lipiodol was densely and homogeneously retained within the whole
      tumor. The number of tumors was single in all diagnostic images. Macroscopic view
      of HCCs were single nodular type in nine cases and single nodular type with extra
      growth in four cases. Clear capsular formation was seen in each HCC nodule. Soft
      x-rays were taken to observe the exact distribution of Lipiodol in the operative
      specimens. Microscopic intrahepatic metastases were found histologically in four
      cases. Histologic examination showed the trabecular pattern with broad blood
      spaces in which Lipiodol was positive with Sudan III staining. Necrosis was seen
      not only in the main tumor, but also in the capsular invasions and microscopic
      metastases with Lipiodol deposition. The characteristics of the cases with total
      tumor necrosis were as follows. Deposition of Lipiodol throughout the tumor was
      essential, and clinically the cases showed a single HCC tumor with a diameter of
      more than 5 cm and arterial hypervascularity. The pathologic findings included
      expansive growth with capsular formation and trabecular-type HCC with abundant
      blood spaces. These findings are important for evaluating the radical efficacy of
      L-TAE.

PMID- 9151921
TI  - Appraisal of combination treatment for hepatocellular carcinoma: long-term follow
      up and lipiodol-percutaneous ethanol injection therapy.
AB  - Since 1988, 124 patients with hepatocellular carcinoma were treated in our
      departments. Among them, 31 cases treated by surgical resection and 30 cases
      administered a combination therapy (Lipiodol [Laboratoire Guerbet, Villepinte,
      France]-transcatheter arterial embolization [L-TAE] and lipiodol-percutaneous
      ethanol injection therapy [L-PEIT]) were analyzed retrospectively. The 1-, 3-,
      and 5-year survival rates were, respectively, 89.0%, 72.7%, and 63.6% for the
      surgical resection group and 93.3%, 72.8%, and 42.0% for the combination therapy
      group. The follow-up results at less than 4 years after the procedures revealed
      that the survival rate with the combination therapy was slightly better than that
      with the surgical treatment. However, in the subsequent 4 years, the survival
      rate of the combination therapy group decreased rapidly. The reasons for this
      deterioration were local recurrence and/or new primary lesions of hepatocellular
      carcinoma, mainly due to inappropriate ethanol injection. To achieve adequate and
      accurate injection of ethanol, a 10% volume of Lipiodol was mixed with the
      ethanol so that the location of the injected ethanol could be easily confirmed.
      The effectiveness of L-PEIT was thus confirmed by computed tomography, performed
      on the following day. Defective Lipiodol accumulation in the tumor and/ or
      neighboring tissues was able to be corrected by additional ethanol injections.
      With this L-PEIT technique, the tumor necrosis rate is now improving. Therefore,
      a better prognosis is expected.

PMID- 9151923
TI  - Phase II study of Spherex (degradable starch microspheres) injected into the
      hepatic artery in conjunction with doxorubicin and cisplatin in the treatment of
      advanced-stage hepatocellular carcinoma: interim analysis.
AB  - Patients with advanced-stage unresectable hepatocellular carcinoma (HCC) were
      treated with intrahepatic arterial doxorubicin 30 mg/m2 plus escalating doses of
      cisplatin up to 100 mg/m2 in conjunction with rapid bolus injection of Spherex
      (degradable starch microspheres; Kabi Pharmacia, Lund, Sweden) into the hepatic
      artery, until slowing or reversal of blood flow. Treatments were repeated every 4
      to 6 weeks until progression, or were continued indefinitely if there was disease
      stability or response. Thirty-five evaluable patients have so far been accrued to
      the study. Objective tumor responses have occurred in 22 patients (63%), of whom
      20 had partial responses and two had complete responses. Four of the patients had
      reversal of tumor-induced portal vein thrombus. Toxicities included death, one
      patient (and a death of uncertain cause in an additional patient); hepatitis, two
      patients; pancreatitis, one patient; dyspnea/hypotension, two patients; and
      hepatic artery nontransient thrombosis in four patients. Six patients have
      survived 2 years and an additional 10 patients have survived 1 year. The addition
      of Spherex to intrahepatic arterial chemotherapy for advanced-stage HCC appears
      to be relatively safe and is well tolerated even in patients with portal vein
      thrombosis, which represent the majority of patients with advanced-stage HCC.

PMID- 9151922
TI  - Zinostatin stimalamer-transcatheter arterial embolization for hepatocellular
      carcinoma: a comparison with lipiodol-transcatheter arterial embolization.
AB  - Twenty patients with unresectable hepatocellular carcinoma were treated by
      zinostatin stimalamer-transcatheter arterial embolization (SMANCS-TAE). After
      administration of SMANCS, a superselective catheterization technique was used to
      inject gelatin sponge particles into the artery or artery branch supplying the
      cancer-bearing segment. We compared the results of SMANCS-TAE with Lipiodol
      (Yamanouchi, Tokyo, Japan)-TAE performed during the same period. In 18 of 20
      patients (90%), a tumor necrosis rate of 100% (grade 4) was obtained after one or
      two courses of SMANCS-TAE. The SMANCS group was superior to the Lipiodol-TAE
      group in terms of the tumor reduction rate, alpha-fetoprotein reduction rate, and
      cumulative 1.5-year survival rate, but not significantly. No severe side effects
      were noted after SMANCS-TAE. SMANCS-TAE appears to have potential as a new
      treatment for hepatocellularcarcinoma, and patients treated with this technique
      will be monitored to elucidate the long-term effects.

PMID- 9151924
TI  - Spherex (degradable starch microspheres) chemo-occlusion--enhancement of tumor
      drug concentration and therapeutic efficacy: an overview.
AB  - The efficacy of systemic chemotherapy in the treatment of primary and secondary
      liver cancer is poor. Intra-arterial delivery of fluoropyrimidines resulted in a
      significantly higher tumor response, but survival was prolonged by only a few
      months. Obviously, there is still a great need for improved therapeutic
      strategies. As the regional blood flow is of importance for the advantage of
      intra-arterial administration of cytotoxic drugs, degradable starch microspheres
      (DSMs) have been developed specifically to achieve temporary vascular occlusion
      during coadministration of cytotoxic drugs. Peak plasma concentrations, as well
      as the area under the concentration-time curve (AUC) of mitomycin C in plasma
      have been found to be significantly reduced following intra-arterial
      coadministration with DSMs. Similar results were also obtained with other drugs,
      such as nitrosoureas, doxorubicin, and 5-fluorouracil. The temporary vascular
      occlusion induced by DSMs enables a coadministered drug to be lodged in the
      target area for a prolonged period of time, resulting in a selectively increased
      uptake of labeled low molecular weight markers and several cytotoxic drugs into
      liver tumors compared with normal liver tissue. Vascular occlusion induced by
      DSMs has been demonstrated to redistribute the blood flow to hypovascular areas,
      which might be of particular importance for improving the efficacy of intra
      arterial chemotherapy of hypovascular liver tumors. Passage through arteriovenous
      shunts was generally increased after DSM injection. However, this was without
      clinical significance as respiratory distress symptoms were found in only 1% of
      the sessions and were not considered to be serious in any of these patients. To
      take advantage of the pharmacokinetic modulation of coinjected drugs and, in
      addition, the redistribution of blood flow to hypovascular tumor areas, the goal
      is to achieve an almost complete vascular occlusion by injection of DSMs.
      Therefore, due to the wide variation between patients in the size and vascularity
      of liver tumors, the dose of DSMs has to be individualized. Degradable starch
      microspheres have been shown to enhance the antitumor efficacy of several
      cytotoxic drugs in animal experimental models and in noncomparative and
      randomized clinical studies.

PMID- 9151925
TI  - Indication of chemoembolization therapy without gelatin sponge for hepatocellular
      carcinoma.
AB  - This study evaluated the effect of chemoembolization (C-LIP) consisting of
      ethiodized oil (Lipiodol Ultra Fluid; Andre Guerbet, Aulnay-sous-Bois, France)
      and epirubicin, without gelatin sponge on hepatocellular carcinoma (HCC),
      administered by hepatic arterial infusion. We analyzed the cases from two points
      of view: the local recurrence rate for hypervascular solitary small HCC (tumor
      size: < or =3 cm in diameter) and the cumulative survival rate for advanced HCC
      (stage VI according to the criteria of Liver Cancer Group of Japan) following C
      LIP therapy. The C-LIP also was compared with transcather arterial embolization
      (TAE; C-LIP followed by gelatin sponge) and percutaneous ethanol injection
      therapy (PEIT). In the small HCC cases, the recurrence rate at 1 year after C-LIP
      was 77% (10 of 13 patients), while the local recurrence rate was 46% (six of 13
      patients) at 6 months and 61% (eight of 13 patients) at 1 year. The local
      recurrence rate at 1 year was 29% (four of 14 patients) after TAE and 20% (three
      of 15 patients) after PEIT. These results showed that the effect of local
      anticancer therapy by C-LIP was not as potent as that of TAE or PEIT. In advanced
      HCC cases, the cumulative survival rate for 13 patients treated by C-LIP was 72%
      at 6 months, 36% at 1 year, and 14% at 2 years. However, the survival rates for
      13 patients at 6 months, 1 year, and 2 years after TAE were 46%, 23%, and 8%,
      respectively. There was no difference between the C-LIP patients and TAE patients
      with regard to the pretreatment liver function. Three patients died within 2
      months after the initial TAE. These deaths were mainly due to damage to the
      noncancerous liver parenchyma. Therapy with C-LIP alone was not appropriate for
      hypervascular solitary small HCCs, and additional treatment was necessary. We
      think C-LIP therapy should be selected instead of TAE for advanced HCCs to avoid
      severe parenchymal damage.

PMID- 9151926
TI  - Combined therapy with external beam irradiation and hepatic arterial epirubicin
      infusion through an implanted port for advanced hepatocellular carcinoma.
AB  - Nineteen patients with advanced stage IV hepatocellular carcinoma for which
      transcatheter arterial embolization and percutaneous ethanol injection were not
      indicated have been treated by combined therapy with external beam irradiation
      and repeated hepatic arterial epirubicin infusion through an implanted port. The
      response rate was 47%, and the median survival was 11.6 months (range, 4.0 to
      27.1 months). Eighteen of the 19 patients were able to undergo the infusion
      therapy on an outpatient basis 3 to 7 weeks after initiation of therapy. This
      combined therapy was effective in improving tumor-bearing survival and less
      stressful for the patients because of the minimal therapy-related toxicity and
      brief hospitalization.

PMID- 9151927
TI  - The effect of YNK-01 (an oral prodrug of cytarabine) on hepatocellular carcinoma.
AB  - Thirty-two patients with hepatocellular carcinoma (HCC) were treated with YNK-01,
      a prodrug of cytarabine for oral administration. A dose of 200 mg/d of YNK-01 was
      administered to 17 cases and 300 mg/d to 15 cases. One course was 2 weeks in
      duration, and this was repeated every 4 weeks for as long as the patients were
      able to tolerate it. There were five partial responses (15%) and 13 patients with
      no change (41%). A higher partial response rate was observed in the 300 mg/d
      group (27%) compared with the 200 mg/d group (6%). The average durations of
      partial response and no change were approximately 4 and 3 months, respectively.
      The main side effects of YNK-01 were anemia, leukopenia, thrombocytopenia, and
      symptoms of the alimentary tract (nausea, anorexia, diarrhea, etc). These results
      suggest that YNK-01 is a potentially useful oral agent for chemotherapy of
      hepatocellular carcinoma.

PMID- 9151929
TI  - Hepatic arterial infusion chemotherapy combined with hyperthermia for metastatic
      liver tumors of colorectal cancer.
AB  - The efficacy of combined hepatic arterial infusion chemotherapy and hyperthermia
      for unresectable hepatic tumors of colorectal cancer was retrospectively compared
      with hepatic arterial infusion chemotherapy alone. Nine cases were treated with
      combination therapy and eight cases were treated with hepatic arterial infusion
      alone. The response rate in the combined hepatic arterial infusion/hyperthermia
      group was higher (44% v 25%) and the survival period longer (2-year survival, 35%
      v 12%) than in the group treated with hepatic arterial infusion alone. The
      toxicity was not severe, with the exception of gastrointestinal symptoms,
      suggesting that this combination of modalities is useful in the treatment of
      metastatic liver tumors.

PMID- 9151928
TI  - Regional adjuvant chemotherapy after partial hepatectomy for metastatic
      colorectal carcinoma.
AB  - The prognostic factors after hepatic resection for metastases from colorectal
      carcinoma were examined, and the results of adjuvant hepatic arterial
      chemotherapy are presented. Hepatic resection was undertaken in 57 patients with
      metastatic liver tumor from colorectal cancer. Adjuvant hepatic arterial
      chemotherapy using 5-fluorouracil, doxorubicin or epirubicin, and mitomycin C was
      administered to 31 patients. The 3- and 5-year survival rates for the 57 patients
      were 53% and 23%, respectively. The significant prognostic factors were solitary
      liver tumor and metachronous liver tumor. However, type of hepatectomy, surgical
      margin, site of the primary tumor, and histologic differentiation of the
      carcinoma did not relate to the prognosis. The 3- and 5-year survival rates for
      the patients given adjuvant arterial chemotherapy were 57% and 57%, respectively,
      indicating a significantly better survival rate than in the nontreated patients.
      These results suggest that hepatic arterial chemotherapy is effective treatment
      in patients with hepatic resection for metastases from colorectal carcinoma.
      However, recurrence in the lung is relatively high. Further improvement might be
      achieved by administering hepatic arterial chemotherapy as well as effective
      systemic chemotherapy.

PMID- 9151930
TI  - Efficacy of endoscopic variceal ligation for bleeding esophageal varices in
      patients with tumor thrombus of the portal vein trunk (Vp3) associated with
      hepatocellular carcinoma.
AB  - We studied the efficacy of endoscopic variceal ligation (EVL) in 16 patients with
      tumor thrombus of the portal vein trunk (Vp3) associated with hepatocellular
      carcinoma. The average (+/-SD) number of O rings used was 9.0 +/- 5.0 for the
      esophageal varices (n = 7) and 16.4 +/- 4.5 for the esophagogastric varices (n =
      9). The variceal size was quickly reduced in 11 of the 13 cases whose therapeutic
      outcome was able to be assessed by endoscopy. The red color sign improved in 10
      of the 13 cases, but the therapeutic end point (F0, RC-) was achieved in only two
      patients, who were also treated by endoscopic injection sclerotherapy. Emergency
      EVL achieved only short-term survival (17.14 +/- 6.64 days) and transient
      hemostasis. Elective EVL was associated with a survival duration of 90.0 +/-
      64.25 days. The difference in the survival rate between emergency and elective
      cases was significant (P < .05). With regard to the timing of its application,
      EVL, being a less-invasive treatment, should be performed electively before
      variceal rebleeding for those patients with Vp3 hepatocellular carcinoma whose
      liver function is preserved.

PMID- 9151931
TI  - The anxiolytic-like effects of the neurosteroid allopregnanolone: interactions
      with GABA(A) receptors.
AB  - The neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone) was
      administered systemically to rats which were tested in the Geller-Seifter
      conflict paradigm, an established animal model of anxiety. Allopregnanolone was
      found to produce significant anxiolytic-like effects at a dose of 8 mg/kg. When
      three ligands that function at different sites on the gamma-aminobutyric
      acid/benzodiazepine receptor-chloride ionophore complex (GABA(A) receptors) were
      examined in conjunction with allopregnanolone, the anti-conflict effects of
      allopregnanolone were effectively reversed only by the benzodiazepine receptor
      inverse agonist RO15-4513 (ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo
      [1,5-alpha]-[1,4]benzodiazepine-3-carboxylate). Since this inverse agonist has
      been reported to inhibit the GABA(A)-activated chloride flux in neuronal
      membranes, it is likely that the stimulation of the chloride channel in GABA(A)
      receptors is an important component of the effects of allopregnanolone. In
      contrast, the benzodiazepine receptor antagonist flumazenil (ethyl-8-fluoro-5,6
      dihydro-5-methyl-6-oxo-4H-imidazo [1,5-alpha]-[1,4]benzodiazepine-3-carboxylate)
      did not block the anxiolytic-like actions of allopregnanolone, indicating that
      allopregnanolone does not bind at the benzodiazepine site directly.
      Isopropylbicyclophosphate, which binds at the picrotoxinin site on the GABA(A)
      receptors and blocks the behavioral actions of ethanol, also dose-dependently
      reversed the anti-conflict effect of this neurosteroid. The results suggest that
      allopregnanolone may be working either at a site specific for the benzodiazepine
      receptor inverse agonist RO15-4513 or at the picrotoxinin site to produce its
      potent anxiolytic-like behavioral effects.

PMID- 9151932
TI  - 5-HT2C receptors mediate penile erections in rats: actions of novel and selective
      agonists and antagonists.
AB  - The mixed 5-HT2A/5-HT2B/5-HT2C receptor agonist, m-(chlorophenyl)piperazine
      (mCPP), elicited penile erections in rats, an action mimicked by the selective 5
      HT2C receptor agonist, RO 60-0175 (S)-2-(6-chloro-5-fluoroindol-1-yl)-1
      methylethylamine), whereas the preferential 5-HT2B receptor agonist, BW 723C86 (1
      [5-(thienylmethoxy)-1H-3-indoyl] propan-2-amine) was ineffective. The actions of
      mCPP and RO 60-0175 were dose-dependently abolished by the novel 5-HT2B/5-HT2C
      receptor antagonists, SB 200,646 (1-(1-methylindol-5-yl)-3-(3-pyridyl) urea) and
      SB 206,553 (5 methyl-1-(3-pyridil-carbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3 
      f]indole). In contrast, penile erections were not significantly affected by the
      selective 5-HT2B receptor antagonist, SB 204,741 (1-(1-methylindol-5-yl)-3-(3
      methylisothiazol-5-yl)-urea) nor by the selective 5-HT2A receptor antagonist, MDL
      100,907 ([R(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-p
      iperidine-methanol]). These data provide rigorous pharmacological evidence that
      activation of 5-HT2C receptor elicits penile erections in the rat. This model
      should, thus, be of use for characterising novel ligands at this site.

PMID- 9151933
TI  - Regional variation in the effects of nicotine on catecholamine overflow in rat
      brain.
AB  - The effects of acute, repeated intermittent and continuous administration of
      nicotine on the overflow of noradrenaline in the ventral hippocampus and dopamine
      in the nucleus accumbens and striatum have been studied. Daily injections of
      nicotine (0.4 mg/kg(-1) for 5 days) enhanced noradrenaline and dopamine overflow
      in the ventral hippocampus and nucleus accumbens respectively (P < 0.01 and P <
      0.05) but not dopamine in the striatum in response to a nicotine challenge. The
      responses in the ventral hippocampus and nucleus accumbens were attenuated (P <
      0.01) by the constant infusion of nicotine at a dose of 1 mg kg(-1) per day; the
      dopamine response in the striatum required a higher dose (4 mg kg(-1) per day)
      before desensitisation was observed. The data suggest that the dopamine
      projections to the striatum are less sensitive to both stimulation and
      desensitisation by nicotine than the catecholamine projections to the ventral
      hippocampus and nucleus accumbens.

PMID- 9151934
TI  - NS 1619 activates Ca2+-activated K+ currents in rat vas deferens.
AB  - The effects of NS 1619, a newly developed activator of large-conductance Ca2+
      activated K+ channels, were investigated on single smooth muscle fibers
      dissociated enzymatically from rat vas deferens and on contractions of the
      epididymal half of vas deferens. K+ currents were recorded using whole-cell patch
      clamp methods in near-physiological K+ solutions (5.4 mM extracellular K+/145 mM
      intracellular K+). When cell membrane voltage was stepped to test potentials (-60
      to +60 mV) from a holding potential of -10 mV, NS 1619 increased the outwardly
      rectifying K+ current in a concentration-dependent manner. The increased portion
      of the K+ current by NS 1619 was totally abolished by charybdotoxin (100 nM) but
      not by glibenclamide (3 microM). NS 1619 reduced electrically stimulated
      contractile responses of rat vas deferens in a concentration-dependent manner,
      and charybdotoxin but not glibenclamide partially inhibited the effect of NS
      1619. NS 1619 (50 microM) inhibited the noradrenaline-induced contraction.
      Charybdotoxin (100 nM) partially reduced the NS 1619-induced inhibition while
      glibenclamide (3 microM) had no effect. NS 1619 (10-100 microM) reduced the high
      K+-induced contractions in a noncompetitive manner. The present results indicate
      that NS 1619 activates charybdotoxin-sensitive Ca2+-activated K+ channels and
      probably inhibits Ca2+ influx. These two effects might account largely for the
      observed mechanical inhibition induced by NS 1619 in the epididymal half of
      isolated rat vas deferens.

PMID- 9151935
TI  - Modulation of enkephalin release by nociceptin (orphanin FQ).
AB  - Nociceptin (orphanin FQ) is an endogenous peptide agonist for the newly
      discovered receptor (opioid receptor-like 1 receptor, ORL1) that bears striking
      homology to opioid receptors. Initial reports claimed that this peptide had
      hypoalgesic effects following i.c.v. or i.t. administration. The present study
      demonstrates that, in the presence of opioid receptor blockade, nociceptin can
      substantially alter the magnitude of the stimulated release of methionine
      enkephalin from the guinea pig myenteric plexus. This effect is concentration
      dependent. Low doses (1 or 10 nM) inhibit whereas higher concentrations (100 or
      1000 nM) enhance evoked enkephalin release. In contrast, in the absence of opioid
      receptor blockade, a statistically significant inhibition of stimulated
      enkephalin release is observed in response to 1, 100 or 1000 nM nociceptin.
      However, the magnitude of this effect did not differ among these concentrations.
      Furthermore, at 10 nM nociceptin, either an inhibition or enhancement of
      stimulated enkephalin release is manifest. The ability of naloxone to alter the
      nociceptin modulation of enkephalin release suggests that a component of the
      nociceptin modulation of enkephalin release is mediated via opioid receptors.
      This is consistent with the observation that this peptide has modest affinity for
      opioid receptors (L > K > 8) which, under appropriate conditions, should be
      sufficient to permit interactions with multiple opioid receptor types. This
      complicates dose responsiveness for nociceptin since both the naloxone-resistant
      (ORL1-mediated) and naloxone-sensitive (opioid receptor-mediated) component
      exhibit a concentration-dependent bimodality (albeit in opposite directions).
      Determination of i.c.v. or i.t. nociceptin dose responsiveness over several
      orders of magnitude is suggested before concluding the physiological effects of
      this peptide.

PMID- 9151936
TI  - Neurochemical studies with the novel anticonvulsant levetiracetam in mouse brain.
AB  - Levetiracetam is a novel antiepileptic agent with a wide spectrum of activity
      against experimental and clinical seizures. The mechanism of its anticonvulsant
      action remains to be determined. We have investigated the effects of
      levetiracetam on several gamma-aminobutyric acid (GABA)-related neurochemical
      parameters in mouse brain. Adult male mice were randomised into two groups and
      administered levetiracetam (0-300 mg/kg) intraperitoneally either as a single
      dose or twice daily for 5 days. Four hours after the final dose, animals were
      killed and their brains removed. Brain tissues were analysed for concentrations
      of GABA, glutamate and glutamine and for the activities of GABA-transaminase and
      glutamic acid decarboxylase. Single dose and repeated levetiracetam treatments
      were without effect on all of the parameters investigated. The anticonvulsant
      action of levetiracetam is unlikely to be mediated via an action on the GABAergic
      system.

PMID- 9151937
TI  - Heterogeneity of the inhibitory influence of sulfonylureas on prostanoid-induced
      smooth muscle contraction.
AB  - In addition to their hypoglycemic influence, sulfonylureas have been reported to
      inhibit prostanoid-induced vasoconstriction. Using isometric tension measurements
      we investigated whether this inhibitory influence is exerted by different
      sulfonylureas in various types of blood vessels from different species and in
      other types of smooth muscle cells. It was found that in addition to
      glibenclamide and tolbutamide also gliclazide (1 mM) and tolazamide (1 mM) block
      contractions induced by prostaglandin F2alpha and the thromboxane A2 mimetic U
      46619 in rat aorta, but not the contractions elicited by norepinephrine,
      serotonin or high potassium. Glibenclamide (10 microM) inhibits the prostaglandin
      F2alpha- and U-46619-induced contractions on rat tail, femoral and renal
      interlobar arteries and on bovine retinal and ciliary arteries, but not those on
      aorta and carotid artery from guinea pigs and on human subcutaneous arteries.
      Glibenclamide (10 microM), tolbutamide (1 mM), tolazamide (1 mM) and gliclazide
      (1 mM) all block contractions induced by U-46619, but not those induced by
      carbachol, on rat intrapulmonary bronchioles. However, prostanoid-induced
      contractions of guinea-pig trachea and main bronchi are not influenced by
      glibenclamide (10 microM). From these results it is concluded that the ability of
      sulfonylureas to block prostanoid-induced contractions is shared by all
      sulfonylureas tested, that this is not limited to vascular smooth muscle cells
      and that it shows a heterogeneity, that might be linked to interspecies
      differences.

PMID- 9151938
TI  - Effect of rilmenidine on arterial pressure and urinary output in the
      spontaneously hypertensive rat.
AB  - Rilmenidine is an antihypertensive agent acting at the imidazoline receptor that
      may have both central effects in the ventral lateral medulla and direct effects
      on the kidney to alter Na+ excretion. The present experiments examined whether
      rilmenidine induces a leftward shift or change in the slope of the pressure
      natriuresis curve in the spontaneously hypertensive rat (SHR). A single oral
      gavage dose indicated that 3 and 10 mg/kg rilmenidine significantly lowers
      arterial pressure at 4-12 h after administration by oral gavage. The effect of
      rilmenidine on pressure-natriuresis was studied using twice daily doses of 1 and
      3 mg/kg for control and treated SHR drinking tap water or 1% NaCl for 3 days. Na+
      excretion was measured over 24 h, and mean arterial pressure was measured 6-8 h
      after the morning dose of rilmenidine. The results indicate that 1 mg/kg had no
      effect, while the pressure-natriuresis relationship for the rats receiving the 3
      mg/kg dose was shifted to the left and was not significantly different from the
      vertical slope of the untreated SHR. This experiment also suggested that
      rilmenidine may attenuate the salt preference of the rats. This was confirmed in
      an additional series of experiments in which the rats had access to both tap
      water and 1% NaCl. Thus, rilmenidine shifts the pressure-natriuresis relationship
      to the left and reduces salt preference in SHR.

PMID- 9151939
TI  - Noradrenergic and peptidergic sympathetic regulation of cutaneous
      microcirculation in the rat.
AB  - Cutaneous microcirculatory changes were measured by laser-Doppler flowmetry in
      response to electrical stimulation of sympathetic efferent fibres of the rat's
      saphenous nerve. After perineural capsaicin (2%) pretreatment, electrical
      stimulation of the peripheral stump of the cut saphenous nerve evoked a reduction
      in blood flow (vasoconstriction) followed by a minimal enhancement. This late
      vasodilatation was further reduced by resiniferatoxin (1 microg/kg i.v.), and
      vasoconstriction was abolished by guanethidine (8 mg/kg i.v.), indicating the
      involvement of sensory and sympathetic fibres in the respective responses. The
      vasoconstrictor response was analysed after blockade of antidromic vasodilatation
      by combined capsaicin-resiniferatoxin pretreatment. alpha-Adrenoceptor
      antagonists (1 mg/kg phentolamine, 0.5 mg/kg prazosin and 1 mg/kg GYKI-12743 (RS
      2-(3)N-(2-benzo;1,4i-dioxanyl)-methylamino(propyl)-3(2H) -piridazinone
      hydrochloride) inhibited, but did not eliminate the blood flow reduction evoked
      by 3 Hz stimulation. At 10 Hz stimulation significant inhibition was obtained
      only with GYKI-12743. No inhibition was observed with propranolol (10 microg/kg)
      on any occasion. A functional neuropeptide Y antagonist, alpha-trinositol (D-myo
      inositol-1,2,6-trisphosphate, PP56; 50 mg/kg i.v.), markedly diminished the
      vasocontrictor response remaining after treatments with the alpha-adrenoceptor
      blocking agents. Inhibition was more pronounced at 10 Hz. Since 3 Hz corresponds
      to an average, and 10 Hz approaches the maximal firing rate of the sympathetic
      efferents, these results emphasise the significant role of neuropeptide Y in
      regulation of the cutaneous microcirculation by sympathetic fibres under
      physiological circumstances, particularly during high activity.

PMID- 9151940
TI  - Potentiation of the insulinotropic and hypoglycemic action of gliquidone by
      succinic acid esters.
AB  - The monoethyl, monopropyl and monoisopropyl esters of succinic acid, administered
      intravenously at the dose of 2 micromol/g body weight, were found to increase the
      insulinotropic action of gliquidone (0.2 nmol/g body weight) in anaesthetized
      rats. The monoisopropyl ester of succinic acid also doubled the hypoglycemic
      action of gliquidone. These findings indicate that it is possible to design
      esters of succinic acid that are devoid of the risk of generating methanol by
      intracellular hydrolysis, and yet susceptible to increase both the insulinotropic
      and hypoglycemic responses to antidiabetic agents.

PMID- 9151941
TI  - Pharmacology of ABT-491, a highly potent platelet-activating factor receptor
      antagonist.
AB  - ABT-491 (4-ethynyl-N, N-dimethyl-3-[3-fluoro-4-[(2-methyl-1H-imidazo-[4,5
      c]pyridin-1-yl)methy l]benzoyl]-1H- indole-1-carboxamide hydrochloride) is a
      novel PAF (platelet-activating factor) receptor antagonist with a K(i) for
      inhibiting PAF binding to human platelets of 0.6 nM. Binding kinetics of ABT-491
      to the PAF receptor is consistent with a relatively slow off-rate of the
      antagonist when compared to PAF. Inhibition of PAF binding is selective and is
      correlated with functional antagonism of PAF-mediated cellular responses (Ca2+
      mobilization, priming, and degranulation). Administration of ABT-491 in vivo
      leads to potent inhibition of PAF-induced inflammatory responses (increased
      vascular permeability, hypotension, and edema) and PAF-induced lethality. Oral
      potency (ED50) was between 0.03 and 0.4 mg/kg in rat, mouse, and guinea-pig. When
      administered intravenously in these species, ABT-491 exhibited ED50 values
      between 0.005 and 0.016 mg/kg. An oral dose of 0.5 mg/kg in rat provided > 50%
      protection for 8 h against cutaneous PAF challenge. ABT-491 administered orally
      was also effective in inhibiting lipopolysaccharide-induced hypotension (ED50 =
      0.04 mg/kg), gastrointestinal damage (0.05 mg/kg, 79% inhibition), and lethality
      (1 mg/kg, 85% vs. 57% survival). The potency of this novel antagonist suggests
      that ABT-491 will be useful in the treatment of PAF-mediated diseases.

PMID- 9151942
TI  - Pentoxifylline decreases brain levels of platelet activating factor in murine
      AIDS.
AB  - Tumor necrosis factor-alpha (TNF-alpha) and platelet-activating factor (PAF) have
      been implicated in the pathogenesis of human immunodeficiency virus (HIV)
      associated encephalopathy. The effects of pentoxifylline on brain PAF levels were
      examined in mice infected with the LP-BM5 murine leukemia virus (MuLV). Seven
      weeks after viral inoculation, significant increases in serum TNF-alpha and brain
      PAF levels were observed. One week of treatment with pentoxifylline initiated 6
      weeks postinfection significantly reduced both serum TNF-alpha and brain PAF
      levels. A significant positive correlation was observed between the levels of
      these substances (r = 0.62; P < 0.01). This study demonstrates that
      pentoxifylline treatment was effective in decreasing the levels of TNF-alpha in
      the serum and PAF levels in the brain of mice infected with the LP-BM5 MuLV.

PMID- 9151944
TI  - Mutational analysis of the putative devazepide binding site of the CCK(A)
      receptor.
AB  - Recently a molecular model was proposed for the binding site of the antagonist
      3S(-)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3-yl) -1H
      indole-2-carboxamide (devazepide) on the cholecystokinin-A (CCK(A)) receptor (Van
      der Bent et al., 1994. Drug Design Discov. 12, 129-148). Fifteen amino acids were
      identified, including hydrophilic ones such as Ser139, Asn349 and Ser379, that
      might interact with the carboxamide moiety in devazepide. To provide mutational
      evidence for this model, wild-type and mutant receptors (S139A, N349A and S379A)
      were transiently expressed and compared with respect to the ability of devazepide
      to inhibit binding of radiolabelled cholecystokinin-(26-33)-peptide amide (CCK-8)
      and CCK-8-evoked Ca2+ mobilization. The data presented suggest the involvement of
      the three residues in antagonist binding, although to a different extent.
      However, it does not seem likely that hydrogen bonds are the driving force in
      view of the relatively minor changes in receptor affinity and activity.

PMID- 9151943
TI  - Functional link between tyrosine phosphorylation and human serotonin transporter
      gene expression.
AB  - Treatment of the JAR human placental choriocarcinoma cells with herbimycin A, an
      inhibitor of tyrosine kinases, led to an increase in the activity of the
      serotonin transporter. This effect was accompanied by an increase in the
      serotonin transporter density and in the steady-state levels of the serotonin
      transporter mRNA. A treatment time of > 4 h was necessary for herbimycin A to
      elicit its effect. Actinomycin D and cycloheximide blocked the effect. There was
      no increase in the steady-state levels of the serotonin transporter mRNA when
      cells were treated with herbimycin A in the presence of actinomycin D. The
      herbimycin A-induced increase in the transporter activity was abolished by
      genistein, another inhibitor of tyrosine kinases. But the increase in the
      transporter mRNA levels caused by herbimycin A was not affected by genistein.
      Treatment of cells with herbimycin A resulted in an increase in the tyrosine
      phosphorylation of specific cellular proteins, suggesting that herbimycin A
      directly or indirectly activates specific tyrosine kinases. It is concluded that
      tyrosine phosphorylation is an essential component in the signaling pathways
      participating in the regulation of the human serotonin transporter gene
      expression.

PMID- 9151945
TI  - Effects of neuroamines and divalent cations on cloned and mutated ATP-gated
      channels.
AB  - Sensitivities to dopamine, 5-hydroxytryptamine, Zn2+ and Cd2+ were studied in
      P2X1, P2X2, P2X3 and P2X4 purinoceptors and mutants of P2X2 purinoceptors
      expressed in Xenopus oocytes. Dopamine (10 and 100 microM) and 5
      hydroxytryptamine (1 to 100 microM) enhanced the inward current activated by
      extracellular ATP through P2X2 and P2X4 purinoceptors. Zn2+ (1 to 100 microM) and
      Cd2+ (10 microM to 1 microM) enhanced the current through P2X2 purinoceptors. As
      for P2X4 purinoceptors, the ATP-activated current was, however, enhanced after
      the washout of Zn2+ (100 microM) or Cd2+ (1 mM). Three mutants of P2X2
      purinoceptors were constructed by substituting negatively charged amino-acid
      residues. The magnitude of the enhancement by Zn2+, Cd2+ and dopamine was
      attenuated when Asp221 was replaced by histidine. The results suggest that
      dopamine, Zn2+ and Cd2+ require some common motif for the current enhancement.

PMID- 9151946
TI  - 'Wide-spectrum Ca2+ channel antagonists': lipophilicity, inhibition, and recovery
      of secretion in chromaffin cells.
AB  - Repetitive application of short depolarizing K+ pulses (70 mM K+, 2 mM Ca2+ Krebs
      HEPES solution, for 10 s every 5 min) produced reproducible catecholamine
      secretory responses from superfused bovine chromaffin cells. At 10 microM for 15
      min, the piperazine derivatives dotarizine, flunarizine and lidoflazine inhibited
      secretion by around 90%; cinnarizine halved the secretory response. Recovery of
      secretion after 30-min washout with Krebs-HEPES solution amounted to 75% in the
      case of dotarizine, 8% for flunarizine, 46% for lidoflazine and 21% for
      cinnarizine. The benzothiazol derivatives (10 microM) (+)-S-lubeluzole and R91154
      (the (-)-R-enantiomer of lubeluzole) blocked the response by 75%; sabeluzole
      inhibited secretion by only 34% and R56865 (N-[1-(4-(4-fluorophenoxy)butyl]-4
      piperidinyl-N-methyl-2-benzo-thiaz olamine) by 61%. Recoveries were around 70% in
      the case of these four benzothiazol derivatives. The diphenylbutyl-piperazine
      derivatives fluspirilene and penfluridol inhibited secretion by over 80%; no
      recovery was produced after 30-min washout. The inhibition of secretion was time
      dependent, as the recovery of the response was. Blockade of secretion by
      dotarizine and flunarizine occurred even in the absence of intermittent K+
      stimulations of the cells. No obvious correlation was seen between the
      octanol/water partition coefficients of the ten compounds tested (that ranged
      between 6 and 4.61), the rate and extent of blockade of secretion, and the
      recovery of the secretory response upon washout. Rather than non-specific actions
      on ion channels (and secretion) due to their high lipophilicity, we believe that
      blockade of various Ca2+ channels relates to their binding properties to specific
      channel micro and macrodomains, as the case might be for 'narrow' (omega
      conotoxin GVIA) and 'wide-spectrum' (omega-conotoxin MVIIC) peptide toxins.

PMID- 9151947
TI  - Leukocyte adhesion--structure and function of human leukocyte beta2-integrins and
      their cellular ligands.
AB  - Leukocyte adhesion is of pivotal functional importance and this has resulted in
      extensive research and rapid development in the field. Leukocyte adhesion
      involves members of three molecular families: integrins, members of the
      immunoglobulin superfamily and carbohydrate binding selectins and sialoadhesins.
      Recently, considerable structural information on leukocyte integrins and members
      of the immunoglobulin superfamily of adhesion molecules has been obtained. This
      fact, combined with the identification of several novel adhesion molecules, has
      increased our understanding of how they function at the molecular level.
      Furthermore, the important issue of how integrins are activated to become
      adhesive is rapidly advancing. It is clearly evident that the knowledge
      accumulated from basic research will increasingly be applied in clinical
      medicine. In this review we focus on two important families of adhesion
      molecules, the leukocyte-specific beta2-integrins and their ligands, the
      intercellular adhesion molecules. Emphasis is put on their structural/functional
      relationships, their mode of regulation and on novel adhesion molecules recently
      discovered.

PMID- 9151948
TI  - Bilirubin oxidation provoked by endotoxin treatment is suppressed by feeding
      ascorbic acid in a rat mutant unable to synthesize ascorbic acid.
AB  - We examined the possibility that bilirubin oxidation is provoked in vivo by using
      scurvy-prone ODS-od/od rats treated with endotoxin (lipopolysaccharide).
      Recently, bilirubin oxidative metabolites were isolated from human urine and
      named biotripyrrin-a and biotripyrrin-b. In ODS-od/od rats fed an ascorbic-acid
      free diet, the concentration of bilirubin metabolites in urine was increased 7.0
      fold at 3 h after injection of lipopolysaccharide and 4.4-fold at 10 h compared
      to the control rats injected with saline. The dietary supplement of ascorbic
      acid, the physiological antioxidant, suppressed the increase in bilirubin
      metabolites in urine after lipopolysaccharide injection: concentrations of
      biotripyrrin-a and biotripyrrin-b in urine collected 6.5-10 h after the injection
      were lower in rats fed an ascorbic-acid-supplemented diet than in rats fed an
      ascorbic-acid-free diet. Moreover, feeding of ascorbic acid suppressed the
      hepatic mRNA level of heme oxygenase-1, the rate-limiting enzyme of bilirubin
      biosynthesis, in rats injected with lipopolysaccharide. These findings indicate
      that bilirubin oxidation is markedly stimulated in lipopolysaccharide-treated
      rats and suggest that bilirubin and ascorbic acid have physiologically protective
      effects against oxidative stress.

PMID- 9151949
TI  - Characterization of the basal and pheromone-stimulated phosphorylation states of
      Ste12p.
AB  - The Saccharomyces cerevisiae transcription factor Ste12p is required for basal
      and activated expression of pheromone-responsive genes, and for invasive growth
      in haploid cells. In diploid yeast, Ste12p is implicated in pseudohyphal
      development. The ability of Ste12p to effect these various responses in three
      different cell types must require stringent regulation of its transcriptional
      activation function and interaction with additional transcription factors. We
      have examined the phosphorylation state of Ste12p in untreated and pheromone
      treated haploid cells, and found eight constitutively phosphorylated peptides.
      Phosphorylation at the constitutive sites does not require the protein kinases of
      the pheromone-response pathway. Treatment of haploid yeast with mating pheromone
      causes the appearance of novel relatively minor phosphorylations on Ste12p. Brief
      [35S]methionine labeling reveals novel pheromone-dependent, electrophoretically
      slower migrating Ste12p species. Similarly, the sole difference we observe in
      tryptic phosphopeptides generated from Ste12p from pheromone-treated and
      untreated cells is the transient appearance of two novel minor hydrophobic
      phosphopeptides. The pheromone-dependent phosphorylation of Ste12p requires an
      intact pheromone-response pathway and localization of Ste12p to the nucleus, but
      does not require the Ste12p DNA-binding domain. We conclude from these
      experiments that the pheromone-response pathway induces the formation of specific
      hyperphosphorylation on Ste12p, which can only be detected as apparently minor
      modifications in vivo. We argue that, if Ste12p is regulated by direct pheromone
      responsive phosphorylation, then that phosphorylation must be represented by the
      two novel phosphopeptides. However, we cannot exclude the possibility that
      pheromone-responsive transcription is controlled by direct phosphorylation of a
      target other than Ste12p.

PMID- 9151950
TI  - A second isoform of 3-ketoacyl-CoA thiolase found in Caenorhabditis elegans,
      which is similar to sterol carrier protein x but lacks the sequence of sterol
      carrier protein 2.
AB  - We cloned a full-length cDNA of the nematode Caenorhabditis elegans that encodes
      a 44-kDa protein (P-44, 412 residues) similar to sterol carrier protein x (SCPx).
      Mammalian SCPx is a bipartite protein: its 404-residue N-terminal and 143-residue
      C-terminal domains are similar to 3-ketoacyl-CoA thiolase and identical to the
      precursor of sterol carrier protein 2 (SCP2; also termed non-specific lipid
      transfer protein), respectively. P-44 has 56% sequence identity to the thiolase
      domain of SCPx but lacks the SCP2 sequence. Northern blot analysis revealed only
      a single mRNA species of 1.4 kb, which agrees well with the length of the cDNA
      (1371 bp), making it improbable that alternative splicing produces an SCPx-like
      fusion protein. The sequence similarities of P-44 to conventional thiolases are
      lesser than that to SCPx. Purified recombinant P-44 cleaved long-chain 3-ketoacyl
      CoAs (C(8-16)) in a thiolytic manner by the ping-pong bi-bi reaction mechanism.
      The inhibition of P-44 by acetyl-CoA was competitive with CoA and non-competitive
      with 3-ketooctanoyl-CoA. This pattern of inhibition is shared with SCPx but not
      with conventional 3-ketoacyl-CoA thiolase, which is inhibited uncompetitively
      with respect to 3-ketoacyl-CoA. From these results, we concluded that nematode P
      44 and mammalian SCPx constitute a second isoform of thiolase, which we propose
      to term type-II 3-ketoacyl-CoA thiolase.

PMID- 9151951
TI  - Purification and characterisation of cathepsin B mRNA 3'-untranslated-region
      binding protein (CBBP), a protein that represses cathepsin B mRNA translation.
AB  - We reported that the 3'-untranslated region (3'-UTR) of cathepsin B mRNA of
      Sarcophaga peregrina (flesh fly) is necessary for the repression of its
      translation, and detected the 3'-UTR-binding protein in lysates of larval
      hemocytes in which cathepsin B mRNA translation was repressed [Yano, T., Kurata,
      S. & Natori, S. (1995) Eur. J. Biochem. 234, 39-43]. In this study, we purified
      the 3'-UTR-binding protein from an embryonic cell line of Sarcophaga. The
      purified protein (CBBP) was found to repress cathepsin B mRNA translation in a
      rabbit reticulocyte lysate. We found that the CBBP contents of the hemocytes did
      not change during metamorphosis, although the cathepsin B mRNA became
      translatable only at the pupal stage. Moreover, we found that pupal, but not
      larval hemocytes, contained a factor that inhibited the binding of CBBP to the 3'
      UTR. A regulatory mechanism of cathepsin B expression in Sarcophaga hemocytes is
      discussed.

PMID- 9151952
TI  - Intracellular location, complex formation, and function of the transporter
      associated with antigen processing in yeast.
AB  - Peptide transport across the membrane of the endoplasmic reticulum (ER) gains
      increasing importance in view of its potential function in selective protein
      degradation and antigen processing. An example for peptide transport in the ER is
      the transporter associated with antigen processing (TAP), which supplies peptides
      for the formation of major-histocompatibility-complex class-I complexes. Here, we
      have expressed human TAP1 and TAP2 in the yeast Saccharomyces cerevisiae.
      Expression of both genes resulted in the formation of a stable TAP heterodimer
      that was localized mainly in the ER. Although a minor fraction of TAP is found in
      the plasma membrane, TAP is unable to restore a-factor secretion in a mutant cell
      line that lacks the yeast mating-factor transporter Ste6. Nevertheless, in vitro
      studies with microsomal vesicles demonstrated that the TAP complex is fully
      functional in the ER membrane in terms of selective peptide binding, ATP
      dependent transport, and specific inhibition by the viral protein of herpes
      simplex virus ICP47. This offers opportunities for topological, structural and
      mechanistic studies as well as genetic screenings for TAP functionality.

PMID- 9151953
TI  - Denaturation and reactivation of dimeric human glutathione reductase--an assay
      for folding inhibitors.
AB  - Human glutathione reductase (GR; which catalyzes the reaction NADPH + GSSG + H+ -
      > 2 GSH + NADP+) is an obligatory FAD-containing homodimer of known geometry.
      Native human GR, a potential target of antimalarial and cytostatic agents, cannot
      be dissociated by dilution or by means of subunit-interface mimetics, similarly
      to well-studied viral dimeric proteins. However, ab initio folding and/or
      dimerization of human GR can be inhibited by point mutations or by peptides
      corresponding to subunit-interface areas, for example synthetic peptide P11,
      which represents the intersubunit-contact helix H11. The structure of this
      peptide, which might assist inhibitor design, was solved by high-resolution NMR
      spectroscopy. Residues 440-453, were found to be alpha helical in the isolated
      peptide. To quantitate the efficacy of inhibitors such as P11, we developed the
      following unfolding/reactivation assay. The effects of various guanidine
      hydrochloride (Gdn/HCl) concentrations were studied by analytical
      ultracentrifugation. It was shown that human GR denatured by greater than 3 M
      Gdn/HCl is monomeric and free of FAD. Circular-dichroism experiments at 223 nm
      indicated a half-life of approximately 20 s at 20 degrees C for the unfolding
      process. To optimize the reactivation yield, four parameters [protein
      concentration (x) in the range 0.3-10 microg/ml, cofactor supplementation,
      temperature (y: 0-32 degrees C), and time (0-72 h)] were varied systematically,
      and a reactivation score z was given to each constellation of parameters. This
      type of analysis might be useful to optimize refolding and activation yields for
      other proteins. For human GR, the highest recovery was found not to occur at one
      of the corners of the x,y plane, but close to its center. Consequently, the
      optimal assay conditions for folding and dimerization inhibitors are as follows.
      The enzyme (at 300 microg/ml) is denatured by 5 M guanidine hydrochloride/5 mM
      dithiothreitol, then reactivated by dilution to 1 microg/ml at pH 6.9 and 20
      degrees C. In the absence of inhibitors, this procedure leads to 70% of the
      control activity within 8 h. Peptides representing the upper subunit interface
      (for instance residues 436-478) of human GR were found to inhibit refolding with
      EC50% values in the micromolar range, whereas fragments from other regions of the
      protein had no influence on this process. For peptide P11, the EC50% value was 20
      microM. In conclusion, hGR, enzyme with a tight intersubunit contact area of 21
      nm2, appears to be suitable for studying protein folding, dimerization, and
      prosthetic-group complexation in the absence and presence of compounds that
      inhibit these processes. There is a shortage, at least for oligomeric enzymes of
      eukaryotes, of published systematic studies on protein (re)activation.

PMID- 9151954
TI  - cDNA cloning and expression of chicken aminopeptidase H, possessing endopeptidase
      as well as aminopeptidase activity.
AB  - Chicken aminopeptidase H is a cysteine protease possessing endopeptidase as well
      as aminopeptidase activity [Rhyu, M. R., Nishimura, T., Kato, Y., Okitani, A. &
      Kato, H. (1992) Eur. J. Biochem. 208, 53-59]. This enzyme exhibits molecular
      masses of 400 kDa on gel filtration and 52 kDa on SDS/PAGE, indicating that it
      consists of eight subunits with the same molecular mass. In the current study, we
      cloned the cDNA for the catalytic subunit of chicken aminopeptidase H. The open
      reading frame of the aminopeptidase H gene consists of 1362 base pairs encoding a
      52-kDa protein consistent with the molecular mass determined on SDS/PAGE; the
      deduced amino acid sequence contains all the partial sequences determined for the
      purified enzyme. The sequence is similar to that of the bleomycin hydrolase of
      rabbit lung, which has been partially determined. The recombinant 52-kDa protein
      expressed in COS7 cells exhibited both aminopeptidase and endopeptidase
      activities, which were inhibited by monoiodoacetic acid. Furthermore, the
      expression of aminopeptidase H in COS7 cells was also recognized on
      immunoblotting. This gene is the first one for aminopeptidase H in an animal
      tissue whose sequence has been completely determined.

PMID- 9151956
TI  - Enzymes of octadecanoid biosynthesis in plants--12-oxo-phytodienoate 10,11
      reductase.
AB  - Octadecanoids, potent cyclic plant signaling molecules derived from alpha
      linolenic acid, are involved in the regulation of a multitude of physiological
      processes such as senescence, herbivore and pathogen defense, mechanoperception
      and morphogenesis. The first cyclic intermediate in the Vick-Zimmerman pathway of
      octadecanoid biosynthesis is 12-oxo-phytodienoic acid. Its conversion to the end
      product of the pathway, jasmonic acid, a C12 compound, first proceeds through
      reduction to 3-oxo-2-(pent-2'-enyl)-cyclopentane-1-octanoic acid, which is then
      converted to jasmonic acid by three cycles of beta-oxidation. The first of these
      conversions is a decisive point in the biosynthetic sequence, in that it channels
      the octadecanoid into the pathway of beta-oxidation. 12-Oxo-phytodienoate
      reductase was purified to apparent homogeneity from a cell suspension culture of
      Corydalis sempervirens. The enzyme is soluble and a monomer of apparent molecular
      mass 41 kDa which prefers NADPH over NADH to reduce the 10,11-double bond of 12
      oxo-phytodienoic acid. The structure of the reaction product was proved by
      derivatization, GC/MS and NMR analysis. The enzyme accepts both the cis and the
      trans isomer of 12-oxo-phydodienoic acid, with a preference for the cis-isomer
      (6:1). 12-Oxo-phytodienoate reductase will also convert the synthetic substrate 2
      cyclohexenone to cyclohexanone, but the enzyme did not reduce some other cyclic
      alpha,beta-unsaturated ketones tested (the plant hormone abscisic acid or the
      steroids testosterone and progesterone). Characteristic parameters of 12-oxo
      phytodienoate reductase were determined.

PMID- 9151955
TI  - The GLY1 gene of Saccharomyces cerevisiae encodes a low-specific L-threonine
      aldolase that catalyzes cleavage of L-allo-threonine and L-threonine to glycine-
      expression of the gene in Escherichia coli and purification and characterization
      of the enzyme.
AB  - The GLY1 gene of Saccharomyces cerevisiae is required for the biosynthesis of
      glycine for cell growth [McNeil, J. B., McIntosh, E. V., Taylor, B. V., Zhang, F
      R., Tang, S. & Bognar, A. L. (1994) J. Biol. Chem. 269, 9155-9165], but its gene
      product has not been identified. We have found that the GLY1 protein is similar
      in primary structure to L-allo-threonine aldolase of Aeromonas jandiae DK-39,
      which stereospecifically catalyzes the interconversion of L-allo-threonine and
      glycine. The GLY1 gene was amplified by PCR, with a designed ribosome-binding
      site, cloned into pUC118, and expressed in Escherichia coli cells. The enzyme was
      purified to homogeneity, as judged by polyacrylamide gel electrophoresis. The
      enzyme has a molecular mass of about 170 kDa and consists of four subunits
      identical in molecular mass. The enzyme contains 2 mol pyridoxal 5'-phosphate/4
      mol of subunit as a cofactor, and its absorption spectrum exhibits maxima at 280
      nm and 420 nm. The enzyme catalyzes the cleavage of not only L-allo-threonine to
      glycine but also L-threonine. We have termed the enzyme a low-specific L
      threonine aldolase to distinguish it from L-allo-threonine aldolase.

PMID- 9151957
TI  - Molecular cloning and functional characterization of the Paracoccus denitrificans
      porin.
AB  - Bacterial porins facilitate the passive uptake of small solutes across the outer
      membrane of the cell. The channel properties and the primary structure of the
      porin from Paracoccus denitrificans were investigated. As judged from single
      channel conductance experiments, this porin forms trimeric pores that show no ion
      selectivity in potassium chloride solution, which indicates that the charges
      within or near the channel are balanced. Based on peptide fragment sequence, the
      gene porG, which codes for this general pore protein, was cloned and analyzed.
      Its primary translation product contains a 20-residue signal sequence, followed
      by the 295 amino acids of the mature protein with a molecular mass of 31.9 kDa.
      Sequence alignments with porins from Rhodopseudomonas blastica and Rhodobacter
      capsulatus and secondary structure predictions suggest a typical rigid barrel
      structure consisting of 16 antiparallel beta-strands.

PMID- 9151958
TI  - Differential stabilization of topoisomerase-II-DNA cleavable complexes by
      doxorubicin and etoposide in doxorubicin-resistant rat glioblastoma cells.
AB  - Using the technique of alkaline filter elution, we have evaluated the DNA damage
      induced by doxorubicin and etoposide in a rat glioblastoma cell line, C6, and its
      doxorubicin-selected resistant variant, C6 0.5. DNA damage paralleled drug
      induced cytotoxicity, but it appeared that the same DNA damage generated much
      less cytotoxicity in resistant cells than in sensitive ones, resistant cells
      being able to tolerate more DNA damage than sensitive cells. We have then
      quantified the doxorubicin- and etoposide-induced complexes between topoisomerase
      II (topoII) DNA with the technique of SDS/KCl precipitation. Etoposide produced a
      concentration-dependent increase in topoII-DNA complexes, which was higher in
      resistant cells at equitoxicity, just as was DNA damage. In contrast, doxorubicin
      induced topoII-DNA complexes, which were much less abundant than those induced by
      etoposide, were not differently produced in sensitive and resistant cells. This
      indicates that the DNA damage occurring in resistant cells at high doxorubicin
      concentrations might originate from source other than topoII-DNA complex
      formation. When verapamil was added during drug exposure, it restored doxorubicin
      intracellular accumulation to the level reached in sensitive cells, partially
      reversed both doxorubicin and etoposide resistance, increased the formation of
      etoposide-induced topoII-DNA complexes, but not those induced by doxorubicin.
      Immunoblot analysis of topoII as well as the measure of its catalytic activity in
      nuclear extracts revealed a quantitative defect of this enzyme in the resistant
      line. When inhibiting this activity by doxorubicin and etoposide, we observed
      that the concentrations of etoposide required for a given inhibition of
      kinetoplast DNA decatenation are much higher that those of doxorubicin. The
      topoII extracted from both cell lines is, therefore, much more sensitive to
      doxorubicin than to etoposide, but no difference in drug sensitivity was evident
      between sensitive and resistant cells, indicating that no qualitative alteration
      in topoII catalytic activity was likely to occur.

PMID- 9151959
TI  - Kinetics of reciprocal pro-urokinase/plasminogen activation--stimulation by a
      template formed by the urokinase receptor bound to poly(D-lysine).
AB  - The two zymogens, plasminogen and pro-urokinase plasminogen activator (pro-uPA),
      constitute a system of reciprocal activation, since plasmin, generated by uPA
      catalysed plasminogen activation, can activate pro-uPA to uPA. Two such zymogens,
      when mixed, will undergo autocatalytic, reciprocal activation resulting in
      generation of proteolytic activity. As an example of reciprocal zymogen
      activation, the plasminogen/pro-uPA system was analysed in terms of a kinetic
      model which describes the progression in activated enzymes. This model gave a
      detailed description of the progress curves in plasmin and uPA. It accounted for
      the effects of varying the concentration of the zymogens, and also for the
      effects of plasmin substrates and inhibitors in the reaction mixture. The model
      assumes non-significant zymogen activity. It did not, however, exclude that a
      very low initial proteolytic activity, accounting for maximally 0.01% of that
      obtained when pro-uPA is fully activated, could be attributed to a genuine pro
      uPA activity. Binding of the uPA receptor (uPAR) to pro-uPA/uPA might affect
      separate steps of the reciprocal activation reaction, or it might induce a
      significant pro-uPA activity. To distinguish between these possibilities the
      effect of a recombinant soluble (residues 1-277) form of uPAR, uPAR-(1-277)
      peptide, on reciprocal pro-uPA/plasminogen activation was studied. uPAR-(1-277)
      peptide attenuated reciprocal zymogen activation, and the results suggested that
      this was due to a decreased accessibility of the pro-uPA/uPAR-(1-277)-peptide
      complex to activation by plasmin. The uPAR-(1-277)-peptide in the presence of
      poly(D-lysine) caused a 20-fold enhancement of reciprocal zymogen activation.
      Kinetic analysis of separate activation steps revealed that this was due to a
      threefold stimulation of plasminogen activation by uPA/uPAR-(1-277)-peptide
      combined with a sixfold stimulation of plasmin's activation of pro-uPA/uPAR-(1
      277)-peptide. The results suggested that poly(D-lysine) provided a template for a
      catalytically favourable interaction between plasminogen/plasmin and the uPAR-(1
      277)-peptide complex with pro-uPA/uPA. There was no indication of a significant
      uPAR-(1-277)-peptide-induced enhancement of pro-uPA activity.

PMID- 9151960
TI  - Kinetic characterization of individual hexose transporters of Saccharomyces
      cerevisiae and their relation to the triggering mechanisms of glucose repression.
AB  - In Saccharomyces cerevisiae, there are a large number of genes (HXT1
      HXT17/SNF3/RGT2) encoding putative hexose transporters which, together with a
      galactose permease gene (GAL2), belong to a superfamily of monosaccharide
      facilitator genes. We have performed a systematic analysis of the HXT1-7 and GAL2
      genes and their function in hexose transport. Glucose uptake was below the
      detection level in the hxt1-7 null strain growing on maltose. Determination of
      the kinetic parameters of individual hexose transporter-related proteins (Hxtp)
      expressed in the hxt null background revealed Hxt1p and Hxt3p as low-affinity
      transporters (Km(glucose) = 50-100 mM), Hxt2p and Hxt4p as moderately low in
      affinity (Km(glucose) about 10 mM), and Hxt6p, Hxt7p as well as Gal2p as high
      affinity transporters (Km(glucosse) = 1-2 mM). However, Hxt2p kinetics in cells
      grown on low glucose concentrations showed a high-affinity (Km = 1.5 mM) and a
      low-affinity component (Km = 60 mM). Furthermore, we investigated the involvement
      of glucose transport in glucose signalling. Glucose repression of MAL2, SUC2 and
      GAL1 was not dependent on a specific transporter but, instead, the strength of
      the repression signal was dependent on the level of expression, the properties of
      the individual transporters and the kind of sugar transported. The strength of
      the glucose repression signal correlated with the glucose consumption rates in
      the different strains, indicating that glucose transport limits the provision of
      a triggering signal rather then being directly involved in the triggering
      mechanism.

PMID- 9151962
TI  - Unusual characteristics of amino-terminal and hydrophobic domains in nuclear
      encoded thylakoid signal peptides.
AB  - Thylakoid transfer signals carry information specifying translocation by either a
      Sec- or delta pH-dependent protein translocator in the chloroplast thylakoid
      membrane, yet all resemble classical signal peptides in overall structural terms.
      Comparison of known transfer signals reveals two differences: (a) signals for the
      delta pH-driven system invariably contain a critical twin-arginine (Arg-Arg)
      motif prior to the hydrophobic (H) domain, whereas known Sec-dependent signals
      contain lysine, and (b) the H-domains of Sec-dependent signals are generally
      longer. Previous work has shown that a twin-Arg motif before the H-domain is
      critical for targeting by the delta pH-dependent pathway; in this report we show
      that the charge characteristics of this region are not important for sorting by
      the Sec pathway. Twin-Lys, twin-Arg or single Arg are all acceptable to the Sec
      system, although single Lys/Arg is preferred. The single Lys in pre-plastocyanin
      can even be replaced by an uncharged residue without apparent effect. We have
      also generated a pre-plastocyanin mutant containing an H-domain which, in terms
      of hydropathy profile, is identical to that of a delta pH-dependent protein. This
      mutant is also transported efficiently by the Sec system, demonstrating that
      hydrophobicity per se is not a key sorting determinant. However, the
      characteristics of the H-domain may be important in avoiding a different form of
      mis-targeting: to the endoplasmic reticulum. Thylakoid signal peptides have
      undergone substantial structural changes during the evolution of the chloroplast
      from endosymbiotic cyanobacterium: plastid-encoded and cyanobacterial signals
      contain H-domains that are highly hydrophobic and enriched in Leu and aromatic
      residues, whereas nuclear-encoded counterparts are Ala-rich and far less
      hydrophobic. We speculate that this trend may reflect a need to avoid
      mistargeting through recognition by cytosolic signal recognition particle, which
      preferentially interacts with more hydrophobic signal peptides.

PMID- 9151961
TI  - Mapping and mutational analysis of the IgE-binding epitopes on Ara h 1, a legume
      vicilin protein and a major allergen in peanut hypersensitivity.
AB  - Peanut allergy is a significant health problem because of the prevelance and
      potential severity of the allergic reaction. Serum IgE from patients with
      documented peanut hypersensitivity reactions and overlapping peptides were used
      to identify the IgE-binding epitopes on the major peanut allergen, Ara h 1. At
      least twenty-three different linear IgE-binding epitopes, located throughout the
      length of the Ara h 1 protein, were identified. All of the epitopes were 6-10
      amino acids in length, but there was no obvious sequence motif shared by all
      peptides. Four of the peptides appeared to be immunodominant IgE-binding epitopes
      in that they were recognized by serum from more than 80% of the patients tested
      and bound more IgE than any of the other Ara h 1 epitopes. Mutational analysis of
      the immunodominant epitopes revealed that single amino acid changes within these
      peptides had dramatic effects on IgE-binding characteristics. The identification
      and determination of the IgE-binding capabilities of core amino acids in epitopes
      on the Ara h 1 protein will make it possible to address the pathophysiologic and
      immunologic mechanisms regarding peanut hypersensitivity reactions specifically
      and food hypersensitivity in general.

PMID- 9151963
TI  - Analysis of backbone dynamics in cytochrome b5 using 15N-NMR relaxation
      measurements.
AB  - Determination of 15N-NMR relaxation rates has allowed the characterisation of the
      dynamic properties of 55 1H-15N bond vectors in a soluble haem-binding domain of
      bovine microsomal ferricytochrome b5 consisting of the first 104 amino acid
      residues. Measurements of heteronuclear [1H]-15N-NMR nuclear Overhauser effects,
      and 15N-NMR longitudinal and transverse relaxation rates have been analysed using
      both model-free and reduced spectral density mapping approaches, demonstrating
      the application of these methods to a paramagnetic system. Analysis reveals that,
      for those regions which have been assessed, the polypeptide backbone of
      ferricytochrome b5 is largely rigid (average S2 = 0.80), and that minimal
      internal backbone motion occurs on the sub-nanosecond timescale. In contrast,
      motions on the microsecond to millisecond timescale, especially pronounced for
      the loop region extending from residues 28 to 31, and which may be of biological
      relevance, are indicated.

PMID- 9151964
TI  - Characterization of the interactions of Alzheimer beta-amyloid peptides with
      phospholipid membranes.
AB  - Increasing evidence suggests that Alzheimer beta-amyloid peptides (AAPbeta) may
      be toxic agents in Alzheimer disease. We investigated the possibility that the
      toxicity may be the result of peptide-lipid interactions, involving either the
      cell membrane or the intracellular vesicular system. The interaction of the
      AAPbeta-(1-40), AAPbeta-(1-42), AAPbeta-(9-25) and AAPbeta-(25-35)-peptides with
      acidic and zwitterionic phospholipids was investigated by means of circular
      dichroism, vesicle disruption and lipid-aggregation assays. These studies were
      undertaken at peptide concentrations approaching in vivo levels and at
      physiological salt concentrations. Circular-dichroism studies demonstrate that
      acidic phospholipids induce a conformational change from random coil to beta
      structure in AAPbeta-(1-40)-peptide and AAPbeta-(1-42)-peptide at pH 6.0. In
      contrast, at pH 7.0, only AAPbeta-(1-42)-peptide was induced to adopt beta
      structure. Phosphatidylinositol was the most efficient inducer of beta structure
      in AAPbeta-(1-42)-peptide. To further investigate the peptide-lipid interactions,
      we examined the ability of the AAPbeta peptides to disrupt and/or aggregate
      phospholipid vesicles. These properties were found to be mediated predominantly
      through electrostatic interactions with the phospholipid headgroup. The data
      presented in this paper have implications for AAPbeta toxicity and senile-plaque
      formation.

PMID- 9151965
TI  - Characterization of the equilibrium intermediates in acid denaturation of human
      stefin B.
AB  - Acid-induced denaturation of recombinant human stefin B was followed using
      circular dichroism (CD) and fluorimetry. By comparing different spectroscopic
      probes, a number of equilibrium intermediates were detected. In pH denaturation
      at very low salt concentration (0.03 M NaCl) four states can be distinguished: N 
      I(N) - I1 - U, where N is the native state, I(N) is a native-like intermediate,
      I1 is an acid intermediate state with properties of a molten globule and U is the
      unfolded state. State 1, exhibits no near-ultraviolet CD but has some residual
      far-ultraviolet CD. It differs from U in its ability to increase fluorescence of
      1-anilino-naphthalene 8-sulfonate (ANS). In 0.42 M salt, the pH denaturation is
      three-state between the dimeric native state N2 and intermediates I(N2) and I2,
      which are also dimeric according to size-exclusion chromatography. The acid
      intermediate I2 is more structured than I1: it binds ANS to a lower extent an I1,
      its Tyr residues are protected from the solvent, it shows some near-ultraviolet
      CD and its far-ultraviolet CD is even more intense than that for the native
      state. 1H-NMR spectra confirmed the overall structural features of the acid
      intermediates. To obtain the enthalpies of unfolding, microcalorimetric
      measurements were performed under conditions where the acid intermediates are
      maximally populated (18 degrees C): state I(N) from pH 5.0 to 4.6, 0.03 M salt:
      state I1 below pH 3.8, 0.42 M salt; and state I1 in equilibrium with I(N) at pH
      4.05, 0.03 M salt. Enthalpies of unfolding for states I(N) and I1 were comparable
      to those of the native state. The enthalpy of unfolding for state I1 could not be
      determined.

PMID- 9151967
TI  - Probing substrate backbone function in prolyl oligopeptidase catalysis--large
      positional effects of peptide bond monothioxylation.
AB  - Site-specific effects on the catalytic activity of prolyl oligopeptidase from
      human placenta were studied using oligopeptide substrates in which a peptide bond
      has been replaced by a thioxo peptide bond. Two series of tetrapeptide-4
      nitroanilides, Ala-Gly-Pro-Phe-NH-Np and Ala-Ala-Pro-Phe-NH-Np, along with all
      possible monothioxylated derivatives, were synthesised and k(cat) and Km values
      were determined for proteolytic cleavage at the Pro-Phe bond. Regardless of
      either Gly or Ala in the P2 subsite, tetrapeptides were rendered uncleavable by
      thioxylation at the Pro-Phe linkage. As a result, Ala-Xaa-Pro-psi[CS-NH]-Phe-NH
      Np (Xaa = Gly or Ala) displayed competitive inhibition with Ki-values of 12
      microM and 44 microM, respectively. Furthermore, in controlling proteolytic
      susceptibility of the substrates, cooperation of the P3-P2 thioxylation site and
      the side chain at the P2 subsite was obtained. Thioxylation at this position
      enhanced k(cat)/Km fivefold in the Gly series, but led to a 1.7-fold decrease in
      the Ala series of substrates. With respect to the Xaa-Pro peptide bond, all of
      the substrates underwent cis/trans isomerisation, thus presenting two stable
      conformers to the protease. However, the magnitudes of the isomerisation
      constants suggested that neither isomerisation rates nor cis/trans equilibria can
      explain the effect of thioxylation on the steady-state constants of proteolysis.

PMID- 9151966
TI  - Functional expression of Fasciola hepatica cathepsin L1 in Saccharomyces
      cerevisiae.
AB  - A cDNA encoding the complete precursor of a Fasciola hepatica cathepsin L
      protease was isolated and sequenced. Functionally active enzyme was expressed and
      secreted by Saccharomyces cerevisiae transformed with a plasmid carrying the
      complete gene. Experiments with temperature-sensitive yeast mutants showed that
      the enzyme is trafficked through the yeast secretory pathway. Yeast transformed
      with a truncated gene, which lacked the pre-peptide-encoding and most of the pro
      peptide-encoding sequences, did not express funtionally active enzyme. The yeast
      expressed enzyme exhibited physicochemical properties in common with the native
      enzyme including, pH optimum for activity, stability at 37 degrees C and ability
      to cleave gelatin and immunoglobulin. Enzyme kinetic data showed that the native
      and yeast-expressed cathepsin L1 have similar specificities for substrates with
      hydrophobic residues in the P2 position. This is the first report of the
      functional expression of a cathepsin L proteinase in S. cerevisiae that did not
      require the use of yeast secretory signal sequences.

PMID- 9151968
TI  - Overexpression of the coenzyme-F420-dependent N5,N10
      methylenetetrahydromethanopterin dehydrogenase gene from the hyperthermophilic
      Methanopyrus kandleri.
AB  - The mtd gene encoding coenzyme-F420-dependent N5,N10
      methylenetetrahydromethanopterin dehydrogenase (Mtd) in the hyperthermophilic
      Methanopyrus kandleri has been cloned, sequenced and functionally overexpressed
      in Escherichia coli. The overproduced enzyme was purified in a 90% yield to
      apparent homogeneity by means of only one chromatographic step. Its
      thermostability properties and most of its catalytic properties were the same as
      those of the native enzyme purified directly from M. kandleri. Only the
      dependence of the activity on the concentration of lyotropic salts differed
      slightly. Northern blot analysis revealed that in M. kandleri the mtd gene is
      monocistronically transcribed.

PMID- 9151969
TI  - Identification and activation of profollipsin, a latent precursor form of porcine
      follipsin.
AB  - A latent protease has been identified in column fractions obtained during the
      purification of the porcine ovarian serine protease follipsin. The latent enzyme
      was readily activated by trypsin treatment. The trypsin-activated enzyme was
      purified using a benzamidine-Sepharose 6B column and was shown to be composed of
      two distinct, covalently associated polypeptides with Mr of 45000 and 32000. This
      polypeptide chain composition, together with its substrate specificity,
      inhibition profile using various protease inhibitors, cross-reactivity with anti
      follipsin antibody, and ability to activate single-chain precursor tissue
      plasminogen activator, indicated its identity as porcine follipsin. The
      activation of the enzyme with trypsin was found to occur by the hydrolysis of an
      internal peptide bond resulting in a two-chain structure. Thus, we conclude that
      the latent enzyme is the inactive precursor form (profollipsin) of follipsin. The
      present study also shows that the follicular fluid of porcine ovary contains a
      profollipsin-activating enzyme activity.

PMID- 9151970
TI  - Kinetic investigations with inhibitors that mimic the posthomolysis intermediate
      in the reactions of coenzyme-B12-dependent glycerol dehydratase and diol
      dehydratase.
AB  - Kinetic investigations were performed on the coenzyme-B12-dependent glycerol
      dehydratase and diol dehydratase reactions using 1,2-propanediol as substrate and
      [omega-(adenosin-5'-O-yl)alkyl]cobalamins as mimics of the posthomolysis
      intermediate state of the coenzyme. All the coenzyme-B12 analogues with
      oligomethylene chains (C3-C7) inserted between the central Co atom and the 5' O
      of the adenosine moiety were competitive inhibitors with respect to coenzyme B12.
      The apparent inhibition constants (Ki) of the shorter-chain inhibitors,
      especially the C5 inhibitor, were smaller for both enzymes than those of the
      longer-chain (C6, C7) compounds. These results are in agreement with the expected
      (0.6-0.9 nm) distance between the Co and 5'-methylene paramagnetic centers in the
      posthomolysis intermediate state of coenzyme B12 in these reactions.

PMID- 9151971
TI  - The predominant protein in peroxisomal cores of sunflower cotyledons is a
      catalase that differs in primary structure from the catalase in the peroxisomal
      matrix.
AB  - This paper describes a biochemical study on the protein composition of
      crystalline inclusions (cores) from plant peroxisomes. By SDS/PAGE and
      immunoblotting, a catalase of 59 kDa was identified as the predominant protein
      component in purified cores from sunflower (Helianthus annuus L.) cotyledons. A
      55-kDa catalase was the only additional peptide detected. In contrast to in
      cores, the 55-kDa catalase was the major catalase protein in matrix fractions
      obtained from lysed peroxisomes. These findings suggested two peroxisomal
      populations of catalase differing in molecular structure and subperoxisomal
      compartmentation in sunflower cotyledons. Evidence for different amino acid
      sequences of the two catalases was found by peptide mapping with endoproteinase
      Glu-C, by expressing a cDNA encoding matrix catalase in Escherichia coli, and by
      partial amino acid sequencing of peptide fragments from 59-kDa core catalase.
      These results contradict the previous view that the formation of cores occurred
      via condensation of matrix catalase, and indicate that new concepts on the
      biogenesis and physiological function of plant peroxisomal cores need to be
      developed.

PMID- 9151972
TI  - 1-(5-phospho-beta-D-ribosyl)2'-phosphoadenosine 5'-phosphate cyclic anhydride
      induced Ca2+ release in human T-cell lines.
AB  - 1-(5-Phospho-beta-D-ribosyl)2'-phosphoadenosine 5'-phosphate cyclic anhydride [2'
      phospho-cyclic ADP-ribose, cAdo(2')P(5')PP-Rib] was prepared enzymatically from
      NADP+ using ADP-ribosyl-cyclase from Aplysia californica. The product was
      purified by HPLC and characterized by NMR and mass spectroscopy, by conversion to
      1-(5-phospho-beta-D-ribosyl)adenosine 5'-phosphate cyclic anhydride (cADP-Rib) by
      alkaline phosphatase and by resistance to snake venom phosphodiesterase. cAdo
      (2')P(5')PP-Rib dose-dependently released Ca2+ from an intracellular, non
      endoplasmic reticular Ca2+ pool of permeabilized Jurkat and HPB. ALL T
      lymphocytes. In contrast, the closely related compounds 1-(5-phospho-beta-D
      ribosyl)3'phosphoadenosine 5'-phosphate cyclic anhydride and 1-(5-phospho-beta-D
      ribosyl)cyclic 2',3'-phosphoadenosine 5'-phosphate cyclic anhydride did not
      induce Ca2+-release from permeabilized T cells. The Ca2+ pool sensitive to
      cAdo(2')P(5')PP-Rib partially overlapped with the Ca2+ pool sensitive to cADP-Rib
      recently described in T cells [Guse, A. H., da Silva, C. P., Emmrich, F., Ashamu,
      G. A., Potter, B. V. L. & Mayr, G. W. (1995) Characterization of cyclic adenosine
      diphosphate-ribose-induced Ca2+-release in T-lymphocyte cell lines, J. Immunol.
      155, 3353-3359]. Control experiments suggest that the results were neither due to
      Ca2+ contaminations in the cADP-Rib preparation nor to catabolism of
      cAdo(2')P(5')PP-Rib to cADP-Rib.

PMID- 9151973
TI  - Affinity labeling of Escherichia coli glucosamine-6-phosphate synthase with a
      fructose 6-phosphate analog--evidence for proximity between the N-terminal
      cysteine and the fructose-6-phosphate-binding site.
AB  - Glucosamine-6-phosphate synthase (GlcNP-synthase) catalyzes the formation of
      glucosamine 6-phosphate from fructose 6-phosphate using the gamma-amide
      functionality of glutamine as the nitrogen source. In the absence of glutamine,
      GlcNP-synthase was recently found to catalyze the formation of glucose 6
      phosphate corresponding to a phosphoglucoisomerase-like activity. Here we report
      active-site directed, irreversible inhibition of Escherichia coli GlcNP-synthase
      (k(inact) = 0.60 +/- 0.05 min(-1), Kirr = 1.40 +/- 0.20 mM) by anhydro-1,2
      hexitol 6-phosphates previously known as irreversible inhibitors of
      phosphoglucoisomerase. Enzyme inactivation with the tritiated affinity label,
      followed by tryptic digestion and purification of the radioactive fragments,
      allowed identification of three peptides. Two of them, accounting for 54% of the
      recovered radioactivity, are believed to result from the nucleophilic attack of
      side-chain carboxylates of Glu255 and Glu258 and thiol of Cys300 of the fructose
      6-phosphate-binding site on the epoxide functionality of the inhibitor. The major
      peptide corresponds to derivatization of the N-terminal cysteine from the
      glutamine-binding site by the inhibitor. These results provide evidence for the
      close proximity of glutamine and fructose-6-phosphate-binding sites recently
      suggested by Bearne [Bearne, S. L. (1996) J. Biol. Chem. 271, 3052-3057].

PMID- 9151974
TI  - Structure/function relationship study of Tyr14 and Arg22 in trichosanthin, a
      ribosome-inactivating protein.
AB  - Amino acids Tyr14 and Arg22 in trichosanthin are residues on helix A1 close to
      the active-site cleft. They are invariant in various type-I and type-II ribosome
      inactivating proteins. In this study, Tyr14 was changed to Phe and Arg22 to Lys
      and Leu. Modified proteins were purified, and activities compared by assaying
      their median inhibitory concentration (ID50) on a rabbit-reticulocyte-lysate
      protein-synthesis system. While the ID50 of wild-type trichosanthin was 0.02 nM,
      those for [Phe14], [Lys22], [Leu22] and [Phe14, Leu22]trichosanthin were 0.10,
      0.03, 0.25 and 0.15 nM, respectively. Therefore, compared with Tyr14, Arg22
      appears to play a more important role in trichosanthin. Structural studies on
      [Leu22]trichosanthin showed that two water molecules occupy the space left by the
      side chain of Arg22, and hydrogen bonds exist between these water molecules and
      nearby residues to retain the conformation. The use of intermolecular rather than
      intramolecular hydrogen bonds may have an adverse effect on stability or folding
      of the protein and results in a mild decrease in activity.

PMID- 9151975
TI  - Elongation of N-acetyllactosamine repeats in diantennary oligosaccharides.
AB  - Glycosylated [Asn22]lysozyme has been shown to contain N-acetyllactosamine
      repeats when expressed in chinese hamster ovary (CHO) cells. We find that the
      major portion of N-acetyllactosamine repeats are associated with diantennary
      oligosaccharides. In Lec2 CHO cells, which are deficient in sialylation,
      glycosylated lysozyme is synthesized with increased contents of N
      acetyllactosamine repeats terminating in beta-galactosyl residues. In the Lec2
      cells and the parental CHO cell line, Pro 5, only a minor portion of the
      oligosaccharides in lysozyme are of the triantennary type. Previously, it has
      been shown that the synthesis of N-acetyllactosamine repeats in Asn-linked
      oligosaccharides is enhanced by an increase in the activity of the elongating
      beta-N-acetylglucosaminyl transferase and by the synthesis of beta-1,6-linked
      antennae. The results with glycosylated lysozyme suggest that glycoproteins
      bearing diantennary oligosaccharides can contain several N-acetyllactosamine
      repeats and that the number of the latter can be increased by decreasing the
      activity of the capping sialyl transferases.

PMID- 9151976
TI  - Collagen fibrillogenesis during sea urchin development--retention of SURF motifs
      from the N-propeptide of the 2alpha chain in mature fibrils.
AB  - The sea urchin 2alpha fibrillar collagen chain has a unique amino-propeptide
      structure with several repetitions of a still unknown 140-145-amino-acid, four
      Cys module called SURF (for sea urchin fibrillar module). To follow the
      expression of the amino-propeptide of the 2alpha chain and assign a function to
      this domain, we have overproduced in Escherichia coli several recombinant
      proteins corresponding either to the amino-propeptide or to the amino
      telopeptide. Monoclonal and/or polyclonal antibodies against these recombinant
      proteins allowed us to observe a similar tissue distribution during the first
      stages of development. A signal is first observed at the prism stage as
      intracellular spots in mesenchymal cells. In plutei, immunofluorescence staining
      is observed around the skeleton spicules and as a thin meshwork surrounding the
      mesenchymal cells. At the ultrastructural level, and using antibodies against the
      amino-propeptide, gold particles are observed at the surface of 25 nm thin
      periodic fibrils. By rotary shadowing, these fibrils show a brush-bottle aspect,
      exhibiting at their surface numerous periodically distributed thin rods ended by
      a small globule. These data indicate that the amino-propeptide is maintained
      during fibrillogenesis. As previously suggested, the retention of the amino
      propeptide could play an important role in regulation of the fibril growth. We
      propose that the important region of this amino-propeptide in the widely
      encountered 25-nm-diameter fibrils is the short triple-helical segment. The
      globular part of the amino-propeptide will not only restrict the fibril growth
      but also interact with other neighbouring components and playing, as suspected
      from our immunofluorescence studies, a function during the spiculogenesis of the
      sea urchin embryo.

PMID- 9151977
TI  - C-terminal extension of the H2-activating subunit, HoxH, directs maturation of
      the NAD-reducing hydrogenase in Alcaligenes eutrophus.
AB  - Formation of enzymatically active [NiFe] hydrogenases is dependent on a number of
      posttranslational steps, including metal attachment to a precursor of the
      catalytic subunit, truncation of a small C-terminal peptide from the precursor,
      and oligomerisation of the subunits. Two amino acid replacements were introduced
      by site-directed mutagenesis at the C-terminal proteolytic cleavage site of HoxH,
      the Ni-containing subunit of the cytoplasmic NAD-reducing hydrogenase of
      Alcaligenes eutrophus H16. Replacement of Ala465, the first residue of the 24
      amino-acid cleaved polypeptide, by Pro yielded a form of HoxH that was blocked in
      C-terminal proteolysis. This HoxH subunit, although capable of binding Ni, was
      blocked in formation of a stable tetrameric holoenzyme. In the second mutant, the
      C-terminal extension of HoxH was eliminated by substituting the Ala codon for a
      translational stop codon. Although this mutant subunit was able to form the
      oligomeric holoenzyme, it was devoid of Ni. Both mutant proteins contained only
      traces of H2-activating functions. H2-dependent reduction of NAD and
      benzylviologen, and D2/H+-exchange activity were almost completely abolished,
      while the NADH oxidoreductase activity, mediated by the diaphorase moiety of the
      hydrogenase, was retained. These results allow the following conclusions: the C
      terminal extension of HoxH is neccessary to direct specific Ni insertion into the
      hydrogenase; subunit assembly to the holoenzyme is not dependent on Ni insertion;
      and a precursor with the C-terminal peptide is not competent for assembly.

PMID- 9151978
TI  - Identification and characterization of the genes for mitochondrial ribosomal
      proteins of Saccharomyces cerevisiae.
AB  - We have purified 13 large subunit proteins of the mitochondrial ribosome of the
      yeast Saccharomyces cerevisiae and determined their partial amino acid sequences.
      To elucidate the structure and function of these proteins, we searched for their
      genes by comparing our sequence data with those deduced from the genomic
      nucleotide sequence data of S. cerevisiae and analyzed them. In addition, we
      searched for the genes encoding proteins whose N-terminal amino acid sequences we
      have reported previously [Grohmann, L., Graack, H.-R., Kruft, V., Choli, T.,
      Goldschmidt-Reisin, S. & Kitakawa, M. (1991) FEBS Lett. 284, 51-56]. Thus, we
      were able to identify and characterize 12 new genes for large subunit proteins of
      the yeast mitochondrial ribosome. Furthermore, we determined the N-terminal amino
      acid sequences of seven small subunit proteins and subsequently identified the
      genes for five of them, three of which were found to be new.

PMID- 9151979
TI  - Characterization of four toxins from Buthus martensi scorpion venom, which act on
      apamin-sensitive Ca2+-activated K+ channels.
AB  - Four peptidyl inhibitors of the small-conductance Ca2+-activated K+ channels
      (SK(Ca)) have been isolated from the venom of the Chinese scorpion Buthus
      martensi. These peptides were identified by screening C18 HPLC fractions of the
      crude venom by means of mass analysis by matrix-assisted-laser
      desorption/ionization time-of-flight mass spectrometry, and toxicological tests
      in mice. Edman degradation analysis of the purified peptides showed sequences of
      28-31 amino acids including 6 cysteine residues. Three of the sequences were
      similar to the P01 peptides from Androctonus scorpions, showing 76% sequence
      similarity for the most closely related, named BmP01, and 46% for the other two,
      named BmP02 and BmP03. Like the P01 peptides, these molecules showed a low toxic
      activity in mice after intracerebroventricular injection, and competed (K0.5 > 1
      microM) with iodinated apamin for binding to its receptor site from rat brain,
      which has been proved to be the SK(Ca) channels. The fourth toxin was
      structurally related to the P05/leiurotoxin I toxin family, with 90% similarity,
      and was named BmP05. This toxin exhibited a high toxic activity with lethal
      effects in mice. Due to its small representation in the venom [less than 0.01%
      (by mass)], its biological properties have been assessed on the synthetic
      analogue of BmP05, which was assembled on a solid phase by means of Fmoc
      methodology. The synthetic peptide was physicochemically identical to the natural
      peptide, as shown by comparison of their molecular masses and amino acid
      compositions, and by their coelution after coinjection on capillary
      electrophoresis. These results confirmed the primary structure of BmP05 including
      an amidated C-terminus. Similarly to natural BmP05, synthetic BmP05 produced
      toxic and lethal effects after intracerebroventricular injection in mice (LD50 =
      37 ng), and was able to compete with iodinated apamin for binding to its receptor
      in rat brain (K0.5 = 20 pM).

PMID- 9151981
TI  - Structural and serological characterisation of the O-antigenic polysaccharide of
      the lipopolysaccharide from Acinetobacter strain 90 belonging to DNA group 10.
AB  - Water-soluble lipopolysaccharide (phenol/water extraction) isolated from
      Acinetobacter strain 90, which belongs to DNA group 10, was hydrolysed with 1%
      acetic acid, ultracentrifuged, and water-soluble products finally eluted from a
      Sephadex G-50 column. The major fraction, a polysaccharide, contained D-Gal, D
      GlcNAc, D-GalNAc, and 4,6-dideoxy-4-[(R)-3-hydroxybutyramido]-D-galactose
      (Fuc4NBuOH). The polysaccharide was characterised by means of monosaccharide
      analyses, Smith-degradation, N-deacetylation/deamination, and NMR studies, and
      was shown to have a branched pentasaccharide repeating unit. [structure in text]
      This structure was specifically recognised in western blots and enzyme
      immunoassays by polyclonal rabbit antisera.

PMID- 9151980
TI  - Human pancreatic ribonuclease--deletion of the carboxyl-terminal EDST extension
      enhances ribonuclease activity and thermostability.
AB  - Mammalian ribonucleases constitute one of the fastest evolving protein families
      in nature. The addition of a four-residue carboxyl-terminal tail: Glu-Asp-Ser-Thr
      (EDST) in human pancreatic ribonuclease (HPR) in comparison with bovine
      pancreatic RNase (RNase A) could have adaptive significance in humans. We have
      cloned and expressed human pancreatic ribonuclease in Escherichia coli to probe
      the influence of the four-residue extension and neighboring C-terminal residues
      on the biochemical properties of the enzyme. Removal of the C-terminal extension
      from HPR yielded an enzyme, HPR-(1-124)-peptide, with enhanced ability to cleave
      poly(C). HPR-(1-124)-peptide also exhibited a steep increase in thermal stability
      mimicking that known for RNase A. Wild-type HPR had significantly low thermal
      stability compared to RNase A. The study identifies the C-terminal boundary in
      the human pancreatic ribonuclease required for efficient catalysis.

PMID- 9151982
TI  - Structural and serological characterisation of the O-antigenic polysaccharide of
      the lipopolysaccharide from Acinetobacter junii strain 65.
AB  - A polysaccharide containing rhamnose (Rha) and Gal was isolated by acetic acid
      hydrolysis, followed by gel-permeation chromatography, from the water-soluble
      lipopolysaccharide (phenol/water extracted) from Acinetobacter junii strain 65.
      The polysaccharide was characterised by means of monosaccharide analyses, Smith
      degradation, and NMR studies, and was shown to have a linear pentasaccharide
      repeating unit, as depicted below. This structure was specifically recognised in
      western blots and enzyme immunoassays by polyclonal rabbit antisera. [structure
      in text]

PMID- 9151983
TI  - Expression of bovine beta-lactoglobulin/human erythropoietin fusion protein in
      the milk of transgenic mice and rabbits.
AB  - We have generated several transgenic mouse lines and rabbits expressing
      efficiently (up to 0.3 mg/ml in mice and up to 0.5 mg/ml in rabbits) human
      erythropoietin in their milk as bovine beta-lactoglobulin fusion protein. Human
      erythropoietin cDNA was inserted in frame into exon 5 of the bovine beta
      lactoglobulin gene with a linker oligonucleotide encoding the cleavage site for
      bacterial IgA protease. RNA analysis performed on one lactating transgenic mouse
      and one transgenic rabbit revealed that the fusion gene was expressed almost
      exlusively in the mammary gland, although low amounts of transgene-derived RNA
      were detectable in salivary glands and uterus or in the kidney. The fusion
      protein was specifically cleaved with IgA protease. The erythropoietin part
      obtained upon digestion had a lower molecular mass than recombinant
      erythropoietin produced in Chinese hamster ovary cells. By deglycosylation
      analysis it was shown that the difference in size was due to a different type of
      glycosylation. Biological activity of the fusion protein, as determined by growth
      stimulation of TF-1 erythroleukemia cells, was less than 15% of that of human
      recombinant erythropoietin. Upon digestion of the fusion protein with IgA
      protease, biological activity comparable to that of the recombinant
      erythropoietin was recovered. Transgenic males and virgin females did not show
      signs of enhanced erythropoiesis, but lactating females expressing the transgene
      displayed transient increases in their hematocrit values.

PMID- 9151984
TI  - Visualization of a covalent intermediate between microsomal epoxide hydrolase,
      but not cholesterol epoxide hydrolase, and their substrates.
AB  - Mammalian soluble and microsomal epoxide hydrolases have been proposed to belong
      to the family of alpha/beta-hydrolase-fold enzymes. These enzymes hydrolyse their
      substrates by a catalytic triad, with the first step of the enzymatic reaction
      being the formation of a covalent enzyme-substrate ester. In the present paper,
      we describe the direct visualization of the ester formation between rat
      microsomal epoxide hydrolase and its substrate. Microsomal epoxide hydrolase was
      precipitated with acetone after brief incubation with [1-(14)C]epoxystearic acid.
      After denaturing SDS gel electrophoresis the protein-bound radioactivity was
      detected by fluorography. Pure epoxide hydrolase and crude microsomes showed a
      single radioactive signal of the expected molecular mass that could be suppressed
      by inclusion of the competitive inhibitor 1,1,1-trichloropropene oxide in the
      incubation mixture. In a similar manner, 4-fluorochalcone-oxide-sensitive binding
      of epoxystearic acid to rat soluble epoxide hydrolase could be demonstrated in
      rat liver cytosol. Under similar conditions, no covalent binding of [26
      (14)C]cholesterol-5alpha,6alpha-epoxide to microsomal proteins or solubilized
      fractions tenfold enriched in cholesterol epoxide hydrolase activity could be
      observed. Our data provide definitive proof for the formation of an enzyme
      substrate-ester intermediate formed in the course of epoxide hydrolysis by
      microsomal epoxide hydrolase, show no formation of a covalent intermediate
      between cholesterol epoxide hydrolase and its substrate under the same conditions
      as those under which an intermediate was shown for both microsomal and soluble
      epoxide hydrolases and therefore indicate that the cholesterol epoxide hydrolase
      apparently does not act by a similar mechanism and is probably not structurally
      related to microsomal and soluble epoxide hydrolases.

PMID- 9151985
TI  - A simple mathematical model and practical approach for evaluating citric acid
      cycle fluxes in perfused rat hearts by 13C-NMR and 1H-NMR spectroscopy.
AB  - We propose a simple mathematical model and a practical approach for evaluating
      the flux constant and the absolute value of flux in the citric acid cycle in
      perfused organs by 13C-NMR and 1H-NMR spectroscopy. We demonstrate that 13C-NMR
      glutamate spectra are independent of the relative sizes of the mitochondrial and
      cytosolic compartments and the exchange rates of glutamates, unless there is a
      difference in 13C chemical shifts of glutamate carbons between the two
      compartments. Wistar rat hearts (five beating and four KCl-arrested hearts) were
      aerobically perfused with 100% enriched [2-(13)C]acetate and the kinetics of
      glutamate carbon labeling from perchloric acid extracts were studied at various
      perfusion times. Under our experimental conditions, the citric acid cycle flux
      constant, which represents the fraction of glutamate in exchange with the citric
      acid cycle per unit time, is about 0.350 +/- 0.003 min(-1) for beating hearts and
      0.0741 +/- 0.004 min(-1) for KCl-arrested hearts. The absolute values of the
      citric acid flux for beating hearts and for KCl-arrested hearts are 1.06 +/- 0.06
      micromol x min(-1) x mg(-1) and 0.21 +/- 0.02 micromol x min(-1) x g(-1),
      respectively. The fraction of unlabeled acetate determined from the proton signal
      of the methyl group is small and essentially the same in beating and arrested
      hearts (7.4 +/- 1.7% and 8.8 +/- 2.1%, respectively). Thus, the large difference
      in the Glu C2/C4 between beating and arrested hearts is not due to the important
      contribution from anaplerotic sources in arrested hearts but simply to a
      substantial difference in citric acid cycle fluxes. Our model fits the
      experimental data well, indicating a fast exchange between 2-oxoglutarate and
      glutamate in the mitochondria of rat hearts. Analysis of the flux constant,
      calculated from the half-time of glutamate C4 labeling given in the literature,
      allows for a comparison of the citric acid flux for various working conditions in
      different animal species.

PMID- 9151986
TI  - Differential characterization of neutrophil cytochrome p30 and cytochrome b-558
      by low-temperature absorption and resonance Raman spectroscopies.
AB  - Cytochrome p30, a novel hemoprotein isolated from rabbit peritoneal neutrophils
      [Escriou, V., Laporte, F., Garin, J., Brandolin, G. & Vignais, P. V. (1994) J.
      Biol. Chem. 269, 14007-14014] has been characterized by low-temperature (77 K)
      absorption and resonance Raman spectroscopies. The spectral data have been
      compared with those obtained with neutrophil cytochrome b-558. At room
      temperature, the absorption difference spectra (reduced minus oxidized) of
      cytochrome p30 and cytochrome b-558 could not been distinguished from each other.
      However, at 77 K, significant differences were observed. In particular, the alpha
      band of cytochrome p30 was split whereas that of cytochrome b-558 was
      symmetrical, but particularly broad. The resonance Raman spectra of cytochrome
      p30 provided evidence for the presence of two hemes both in the ferric and
      ferrous states. One of them was a six-coordinated low-spin heme either oxidized
      or reduced whereas the other one was a high-spin heme, five-coordinated in the
      reduced state and six-coordinated in the oxidized state. It is probable that two
      histidine residues constitute the axial ligands of the six-coordinated low-spin
      heme of cytochrome p30. The resonance Raman spectra of cytochrome b-558 allowed
      the detection of a six-coordinated low-spin heme, similar to that found in
      cytochrome p30. The component typical of the high-spin heme of cytochrome p30 was
      however absent in the spectra of oxidized and reduced cytochrome b-558.

PMID- 9151987
TI  - A target of phosphatidylinositol 3,4,5-trisphosphate with a zinc finger motif
      similar to that of the ADP-ribosylation-factor GTPase-activating protein and two
      pleckstrin homology domains.
AB  - We have purified a protein that binds phosphatidylinositol 3,4,5-trisphosphate
      [PtdIns(3,4,5)P3] using beads bearing a PtdIns(3,4,5)P3 analogue. This protein,
      with a molecular mass of 43 kDa, was termed PtdIns(3,4,5)P3-binding protein. The
      partial amino acid sequences were determined and a full-length cDNA encoding the
      protein was isolated from bovine brain cDNA library. The clone harbored an open
      reading frame of 373 amino acids which contained one zinc finger motif similar to
      that of ADP-ribosylation-factor GTPase-activating protein and two pleckstrin
      homology domains. The entire sequence was 83% similar to centaurin alpha, another
      PtdIns(3,4,5)P3-binding protein. The protein bound PtdIns(3,4,5)P3 with a higher
      affinity than it did inositol 1,3,4,5-tetrakisphosphate, phosphatidylinositol 4,5
      bisphosphate, phosphatidylinositol 3,4-bisphosphate, and phosphatidylinositol 3
      phosphate suggesting that the binding to PtdIns(3,4,5)P3 was specific. The
      binding activity was weaker in the mutants with a point mutation in the conserved
      sequences in each pleckstrin homology domain. Introduction of both mutations
      abolished the activity. These results suggest that this new binding protein binds
      PtdIns(3,4,5)P3 through two pleckstrin domains present in the molecule.

PMID- 9151988
TI  - Nuclear factor of activated T cells (NFAT) is a possible target for dexamethasone
      in thymocyte apoptosis.
AB  - Cell death plays a critical role in the generation of an effective immune system.
      During maturation T lymphocytes are generated, censored and eliminated in the
      thymus. These events are temporally associated with developmental changes in the
      levels of transcription factors including NFAT. The NFAT transcription factor
      (nuclear factor of activated T cells) is implicated in the regulation of T
      lymphocyte proliferation and transcriptional activation of genes encoding
      lymphokines. It has been demonstrated that discontinuities in the inducibility of
      NFAT and AP-1 transcription factors occur during transition of immature
      thymocytes into cortical thymocytes which are eliminated by apoptosis. To
      understand the molecular basis of these developmental intrathymic changes, we
      studied DNA-binding activities of transcription factors during dexamethasone
      induced apoptosis of immature thymocytes. We observed a specific loss of NFAT DNA
      binding activity after dexamethasone treatment. It correlated with a selective
      disappearance of one out of two AP-1 complexes. Our data suggest that NFAT
      complex is a possible target in dexamethasone-induced apoptosis.

PMID- 9151989
TI  - Inhibition of malignant cell proliferation by culture media conditioned by
      cardiac or skeletal muscle.
AB  - The present work is an attempt to explain the high resistance of muscles to
      cancer development. We used primary cultures of rat skeletal and cardiac muscle,
      and examined the effect of the supernatant of these cultures (conditioned medium;
      CM) on proliferation of cancer cells. The results demonstrated that CM inhibited
      the proliferation of several types of malignant cells by more than 50%, without a
      significant inhibition on normal cells. Cell cycle analysis revealed that CM
      increased the number of cells in S and G2 phases, suggesting a cytostatic effect
      of CM. For defining the biological properties of the factor(s) which are present
      in the CM, skeletal muscle cultures were grown in chemically defined medium
      (serum free medium). The concentrated sample was applied to a Sephadex G-50
      column and three fractions were obtained. Only one fraction showed inhibitory
      activity. Four protein bands were observed in this fraction, as revealed by SDS
      PAGE. We suggest that some, or all of these proteins are responsible for
      inhibition of tumor cell replication.

PMID- 9151990
TI  - Ricin-binding proteins along the endocytic pathway: the major endosomal ricin
      binding protein is endosome-specific.
AB  - Ricin is internalized after binding at the cell surface via lectin activity of
      the B-chain recognizing terminal galactose residues. Ricin-A chain is then
      translocated to the cytosol from various endocytic structures. Cell death is the
      result of catalytic inactivation of protein synthesis. Using (125)I-ricin
      overlays, we examined the distribution of ricin binding-proteins within highly
      purified preparations of plasma membrane vesicles, endosomes and lysosomes from
      lymphocytes. All compartments of the endocytic pathway had distinct profiles;
      some ricin-binding proteins were present throughout the pathway; others were
      restricted to the plasma membrane and endosomes. The major endosomal protein
      recognized by (125)I-ricin, a 166 kDa glycoprotein, was endosome-specific. When
      endosomal proteins were solubilized before chromatography onto ricin-agarose this
      protein was also by far the major specifically-bound glycoprotein. This 166 kDa
      glycoprotein might be involved in ricin translocation from this compartment.

PMID- 9151991
TI  - Programmed cell death in the honey-bee (Apis mellifera L.) larvae midgut.
AB  - The histochemical and cytochemical localization of acid phosphatase has been used
      in an attempt to map the sites of cellular lysis and death. Reaction product was
      found both in the brush border of the midgut epithelium and in the basal
      membrane. Vacuolar acid phosphatase activity was found in the regenerative
      epithelial cells. Extra-cisternal reaction product was associated with the
      endoplasmic reticulum which was dilated in lysed areas of the cytoplasm. Free
      acid and alkaline phosphatase activity was found in the basal area of the midgut
      epithelial cells and the former also occurred in the haemocoel. In the
      tracheoblastic cells only vacuolar acid phosphatase activity was seen. Chromatin
      aggregates were distributed throughout the nucleus and the nuclear envelope
      showed some infolding. Certain mature epithelial cells proved positive for anti
      histone associated DNA fragmentation indicative of programmed cell death.

PMID- 9151993
TI  - Extra-lysosomal proteolysis and expression of calpains and calpastatin in
      cultured thyroid cells.
AB  - Proteolysis at neutral pH in the soluble fraction of cultured pig thyroid
      epithelial cells was examined using a synthetic calpain substrate, succinyl-Leu
      Tyr-7-amino-4-methylcoumarin. The Ca2+-independent proteolytic activity was
      largely inhibited by substances known to affect cysteine- and metalloproteases,
      whereas no or little effects were obtained with inhibitors affecting serine- and
      aspartic proteases. Addition of Ca2+ did not significantly alter the rate of
      substrate degradation. Biochemical separation via hydrophobic interaction
      chromatography and Western blotting demonstrated the presence of both m-calpain
      (40% of total calpain) and mu-calpain (60%) in confluent thyrocytes.
      Determination of calpastatin activity indicated a 30 times higher level of the
      inhibitor as compared to total calpain activity. Western blotting showed the
      presence of a 110 kD calpastatin form with additional low mol wt forms possibly
      representing fragmentation products. In immunofluorescent stainings, m-calpain
      had a diffuse cytoplasmic distribution whereas mu-calpain was located both in the
      cytoplasm and at the cell-cell contacts. Calpastatin immunoreactivity was mainly
      granular and located close to the nucleus, although a fibrillar distribution was
      also observed. The results show the presence of all components of the
      calpain/calpastatin system and indicate a strict control of calpain activity in
      cultured thyrocytes. The different subcellular distributions of calpains and
      calpastatin suggests that they are compartmentalized and require mobilization to
      interact.

PMID- 9151992
TI  - Monoclonal antibody raised against human mitotic cyclin B1, identifies cyclin B
      like mitotic proteins in synchronized onion (Allium cepa L.) root meristem.
AB  - Cyclin B-like mitotic proteins have been detected in synchronized Allium cepa L.
      root tip cells by using mouse monoclonal anti-cyclin B1 antibody raised against
      human cyclin B1. Immunoblot shows two closely placed isoforms of cyclin B-like
      proteins having an apparent molecular weight around 54 kDa. In vivo [35S]
      methionine labelling followed by immunoprecipitation and autoradiography
      indicates that cyclin B-like proteins are mainly synthesized in the G2 phase of
      the cell cycle and destroyed in late mitosis. Immunoblotting data depict that the
      level of cyclin B-like proteins reaches the maximum at the late G2 to early M
      phase; and it becomes degraded in the late hours of mitosis. Moreover, the cyclin
      B isoforms are stabilized in colchicine-arrested metaphase cells as already
      reported in animal cells.

PMID- 9151994
TI  - Stimulation of collagen synthesis in rat cardiac fibroblasts by exposure to
      hypoxic culture conditions and suppression of the effect by natriuretic peptides.
AB  - Synthesis of type I and type III collagens by rat cardiac fibroblasts was
      stimulated when the cells were cultured under 95% N2/5% CO2 for one hour followed
      by incubation under normoxic conditions for 24 hours. The stimulative effect was
      attenuated by the presence of atrial natriuretic peptide (ANP, 10(-6) M) or brain
      natriuretic peptide (BNP, 10 6 M) in the culture medium. Northern blot analysis
      indicated that alpha1(I) and alpha1(III) collagen mRNA levels were also increased
      by hypoxia, and decreased with the addition of ANP or BNP in a dose-dependent
      manner. These results indicate interaction between intracellular signals of a
      physical stimulus (hypoxic stress) and those of a chemical one (ANP or BNP) and
      demonstrate that both signals regulate collagen synthesis by cardiac fibroblasts
      at the levels of the mRNAs. The results also suggest that natriuretic peptides
      produced by cardiomyocytes in vivo may function as paracrine factors that play a
      role in the prevention of cardiac fibrosis in ischaemic heart diseases.

PMID- 9151995
TI  - The effect of human endothelial cell-derived proteoglycans on human smooth muscle
      cell growth.
AB  - Extracellular proteoglycans (PGs) purified from cultured human arterial
      endothelial cells were tested for their effects on the proliferation of human
      vascular smooth muscle cells (VSMC). Fractions containing perlecan, the basement
      membrane heparan sulphate (HS) PG, the large chondrotin sulphate (CS)
      proteoglycan from connective tissue and other immunoreactive CS did not inhibit
      the proliferation of human VSMC. Native endothelial extracellular matrix, which
      was shown to contain the same PGs, demonstrated a pronounced stimulatory effect
      on the proliferation of human VSMCs. This stimulatory effect was not removed by
      pre-incubation of the matrix with 1 M NaCl, heparin, platelet extract or plasmin.
      These experiments demonstrate that PGs produced by human arterial endothelial
      cells do not inhibit the proliferation of VSMC. These data do not support the
      hypothesis that human endothelial cells, in vivo, control the activation or
      proliferation of VSMCs directly by the secretion of a non-proliferative molecule.
      Instead they support the hypothesis that the endothelial cells counteract intimal
      hyperplasia of VSMC indirectly by providing a barrier from activating factors in
      the plasma.

PMID- 9151996
TI  - Properties of self-reinforced ultra-high-molecular-weight polyethylene
      composites.
AB  - The physical properties of ultra-high-molecular-weight polyethylene (UHMWPE)
      fibre/UHMWPE matrix composites have been characterized. It was found that the
      tensile strength and modulus, and creep resistance, were significantly increased
      after incorporating UHMWPE fibres into a UHMWPE matrix. The longitudinal tensile
      strength of the resulting self-reinforced composite increased with fibre content,
      according to the law of mixtures. The transverse strength did not change for
      fibre content of up to 7%. The double-notch impact strength of the composites was
      higher than plain UHMWPE. There was no difference in wear properties between the
      composites and plain UHMWPE. The cross-section and tensile fracture surfaces of
      the composites were examined by scanning electron microscopy (SEM). Overall
      results indicate that the self-reinforced UHMWPE composites may be good
      candidates for load-bearing biomedical applications.

PMID- 9151997
TI  - In vitro calcified tendon collagen: an atomic force and scanning electron
      microscopy investigation.
AB  - Atomic force microscopy (AFM), scanning electron microscopy and X-ray energy
      dispersive spectroscopy have been performed on decalcified turkey tendons
      submitted to in vitro calcification in order to investigate the morphology and
      the surface relationships between the inorganic phase and the collagen fibres
      during deposition and compare with those found for physiologically calcified
      samples. 'Tapping mode' AFM was used to reduce the vertical force applied to the
      samples, which were examined without any preparation. A further characterization
      has been carried out by means of X-ray diffraction, infrared absorption and
      chemical analyses. The observations indicate that the inorganic phase deposited
      on collagen fibres during in vitro calcification is poorly crystalline B
      carbonated apatite. The composition, structure and dimensions of apatitic
      crystallites, as well as their orientation with respect to collagen fibrils, are
      very similar to those characteristic of physiologically calcified tissues.
      However, the crystallites seem to be nucleated on the fibril surface, without
      appreciably affecting the molecular packing of collagen.

PMID- 9151998
TI  - Characterization of cellular response to silicone implants in rats: implications
      for foreign-body carcinogenesis.
AB  - Foreign-body (FB) carcinogenesis is a classic model of multistage tumour
      development in rodents. Previous studies have demonstrated that the physical
      characteristics of the implant, and not the chemical composition, are the
      critical determinants of tumour development. The recent controversy over silicone
      breast implants has raised questions regarding the potential carcinogenicity of
      lifetime tissue exposure to silicone products. The present study was designed to
      determine whether the inflammatory and fibrotic reactions associated with
      silicone implants are due to a non-specific foreign-body reaction or whether
      these responses reflect the unique chemical composition of silicone. F344 rats
      were implanted subcutaneously with one of three biomaterials: silicone elastomer
      (Group 1); impermeable cellulose acetate filters (Group 2, positive control); or
      porous cellulose acetate filters (Group 3, negative control). The silicone and
      cellulose implants of Groups 1 and 2 have been previously shown to induce
      fibrosarcomas in rodents, whereas the porous cellulose acetate implants of Group
      3 have been shown to be non-carcinogenic. One week and two months after
      implantation, the pericapsular tissues were evaluated using histopathological and
      in situ immunohistochemical analyses. Endpoints included expression of leucocyte
      antigens CD4 (T helper/inducer), CD8 (T suppressor/cytotoxic) and CD11 b/c
      (macrophage), proliferating cell nuclear antigen (PCNA) as an indicator of
      proliferation, and in situ end-labelling (ISEL) of 3'OH DNA strand breaks as an
      indicator of DNA damage and apoptosis. The results indicated that the acute and
      chronic cellular responses to silicone (Group 1) were not different from
      impermeable cellulose filters (Group 2) of identical size and shape, suggesting
      that these responses were not unique to silicone. The inflammatory response to
      the carcinogenic cellulose and silicone implants (Groups 1 and 2) was attenuated
      and associated with the formation of a thick fibrotic capsule. In contrast, the
      porous cellulose filters (Group 3) induced a markedly different cellular response
      in which the inflammatory reaction was more extensive, prolonged and associated
      with minimal fibrosis. Within the fibrotic capsule surrounding the tumorigenic
      implants, but not the non-tumorigenic implants, cell proliferation and apoptotic
      cell death were increased and associated with persistent DNA strand breaks. Taken
      together, the results suggest that the micrometre-scale surface morphology of the
      implant determines the nature of the subsequent cellular response which may
      predispose to tumour development. Further, these studies serve to emphasize the
      critical importance of appropriate physical controls in studies designed to
      evaluate carcinogenic or autoimmune manifestations associated with silicone
      implants in order to rule out the contribution of the chronic foreign-body
      reaction.

PMID- 9151999
TI  - Comparative rheological investigation of crude gastric mucin and natural gastric
      mucus.
AB  - Mucus is a viscoelastic gel covering the entire alimentary tract. It represents a
      pre-epithelial diffusion barrier influencing the drug absorption process. In this
      way the rheological properties of mucus play an important role. The purpose of
      our investigation was to evaluate and compare the rheological properties of
      rehydrated dried crude porcine gastric mucin (Sigma mucin) and isolated natural
      porcine gastric mucus. Two different rheological approaches were used: constant
      shear and oscillatory shear conditions. The results obtained under steady shear
      conditions show that the reduction of apparent viscosity is caused by time, shear
      rate and temperature. With increasing Sigma mucin concentration the rheological
      behaviour changes from time-independent systems fitting in with the Casson model
      to time-dependent systems fitting in with the Herschel-Bulkley rheological model.
      Measurements performed under oscillatory shear conditions clearly show how the
      mechanical response of different concentrated systems has changed from
      dispersions with prevailing plastic to prevailing elastic properties. Mechanical
      deformation and frequency response of natural gastric porcine mucus have shown a
      strong gel structure with elastic properties. Comparing both systems it can be
      concluded that after rehydration of dried crude gastric porcine mucin, a model
      mucus system with rheological properties equivalent to natural mucus cannot be
      obtained.

PMID- 9152001
TI  - Surface-dimpled commercially pure titanium implant and bone ingrowth.
AB  - The purpose of this investigation was to examine the effect of the surface
      macrostructure of a dimpled commercially pure titanium (cp Ti) implant on bone
      ingrowth in vivo by means of histological examination and a push-out test.
      Cylindrical implants were inserted in one femur of each experimental rabbit and
      the animals were killed at 1.5, 3 and 13 months after implantation. The femur
      with the implant of each animal was then examined in a push-out test. The
      fracture surfaces of the bone-implant interface after the push-out test were
      examined under light and electron microscopy. It seems that the dimpled cp Ti
      surface results in the increased retention of the cp Ti implant in bone due to
      interlocking between vital bone and the dimples.

PMID- 9152002
TI  - Preparation of polymeric urease discs by an electron beam irradiation technique.
AB  - A preparation method of immobilized urease discs by an electron beam irradiation
      technique was developed, and the relationship between enzyme activity and
      preparation conditions was investigated. The immobilized urease disc was a thin
      circular film (200 microm, 5 mm phi) that is useful for biomedical applications.
      The activity of urease irradiated with 1 Mrad at room temperature was protected
      by the presence of cysteine. The activity of the immobilized urease discs was
      studied as a function of monomer concentration (80-90%) and the thicker disc gave
      a high activity. The durability of the immobilized urease discs gave a high
      activity. The durability of the immobilized urease discs was evaluated by
      repeated batch enzyme reactions, and a high activity yield (80-85%) was obtained.

PMID- 9152000
TI  - Effect of hydroxyapatite particle size on myoblasts and fibroblasts.
AB  - After surgery, the bone and soft tissues around integrated biomaterials can be
      adversely affected by implant-related factors acting over a period of years.
      However, few studies have directly addressed the effects upon the adjacent soft
      tissue. The present study was designed to test the biological effects of various
      sized hydroxyapatite (HA) particles on myoblasts and fibroblasts. Both the
      myoblasts and fibroblasts were mixed in in vitro culture with 0.1% (1 mg ml(-1))
      of various sized HA particles (0.5-3.0, 37-63, 177-250, 420-841 microm) for 1 h,
      3 h, 1 day, 3 days and 7 days to test their effects on the cell culture. The
      results show that adding HA particles into a cell culture can decrease the cell
      count significantly. The transforming growth factor-beta1 (TGF-beta1)
      concentrations in the culture medium decreased significantly on addition of HA
      particles. When calculated as a ratio to the cell number, the TGF-beta1 titre
      increased most significantly in the groups of medium-sized particles. The
      prostaglandin E2 (PGE2) concentrations in the medium increased significantly. The
      changes in TGF-beta1 and PGE2 concentrations with the smallest particles were
      most significant and persisted longer. The inhibitory effects of the HA particles
      on the cell culture were mediated by the increased synthesis of PGE2. Caution
      should be exercised before considering the use of an HA product which could
      easily break down into a fine powder.

PMID- 9152003
TI  - Action of eugenol as a retarder against polymerization of methyl methacrylate by
      benzoyl peroxide.
AB  - This study was undertaken to examine an effect of eugenol on polymerization of
      methyl methacrylate (MMA) by benzoyl peroxide (BPO) and 2,2'
      azobisisobutyronitrile (AIBN) in the presence of eugenol. The induction period
      and initial rate of polymerization (IRP) were determined from polymerization
      curves of MMA using differential scanning calorimetry (DSC). The induction period
      increased with increasing concentration of eugenol in both BPO and AIBN systems.
      The IRP decreased as the concentration of eugenol in both BPO and AIBN systems.
      The IRP decreased as the concentration of eugenol increased. Its decreasing rate
      in the BPO system was higher than that in the AIBN system. In the BPO system, the
      IRP was reduced to zero at 0.5 mol% of eugenol. Eugenol in the BPO system was an
      efficient retarder, although the decrease in IRP was relatively small, below 0.05
      mol%. Eugenol was an inhibitor even at high concentration in the AIBN system. The
      suppressible effect of eugenol appears to be due to the interaction between free
      radicals from BPO and eugenol.

PMID- 9152004
TI  - The molecular basis of embryonic kidney development.
AB  - The development of the mature mammalian kidney begins with the invasion of
      metanephric mesenchyme by ureteric bud. Mesenchymal cells near the bud become
      induced and convert to an epithelium which goes on to generate the functional
      filtering unit of the kidney, the nephron. The collecting duct system is
      elaborated by the branching ureter, the growth of which is dependent upon signals
      from the metanephric mesenchyme. The process of reciprocal induction between
      ureter and mesenchyme is repeated many times over during development and is the
      key step in generating the overall architecture of the kidney. Genetic studies in
      mice have allowed researchers to begin to unravel the molecular signals that
      govern these early events. These experiments have revealed that a number of
      essential gene products are required for distinct steps in kidney organogenesis.
      Here we review and summarize the developmental role played by some of these
      molecules, especially certain transcription factors and growth factors and their
      receptors. Although the factors involved are far from completely known a rough
      framework of a molecular cascade which governs embryonic kidney development is
      beginning to emerge.

PMID- 9152005
TI  - Expression of the mouse Gli and Ptc genes is adjacent to embryonic sources of
      hedgehog signals suggesting a conservation of pathways between flies and mice.
AB  - The three mouse Gli genes are putative transcription factors which are the
      homologs of cubitus interruptus (ci) in Drosophila. Along with the gene patched
      (Ptc), ci has been implicated in the hedgehog (Hh) signal transduction pathway.
      To assess the role of Gli in embryogenesis, we compared its expression with that
      of Ptc and Hh family members in mouse. We found that Gli and Ptc are expressed in
      similar domains in diverse regions of the developing mouse embryo and these
      regions are adjacent to Hh signals. We also show that Gli is expressed
      ectopically along with Ptc and Shh in Strong's luxoid mutant mice. These results
      are consistent with conservation of the Hh signal transduction pathway in mice
      with Gli potentially mediating Hh signaling in multiple regions of the developing
      embryo.

PMID- 9152006
TI  - Generation of completely embryonic stem cell-derived mutant mice using tetraploid
      blastocyst injection.
AB  - Embryonic stem (ES) cells provide a unique tool for producing specifically
      designed mutations in mice. Here, we describe an alternative approach toward the
      generation of mice which are derived completely from ES cells (ES mice), as
      judged by glucose phosphate isomerase (GPI) analysis, without prior passage
      through the germline. By injecting wild-type and mutant ES cells into tetraploid
      blastocysts, viable and fertile ES mice were generated, suggesting that
      totipotency of ES cells was not affected by long-term culture and experimental
      manipulation in vitro. When ES cell clones harboring a lacZ reporter gene
      introduced by either targeted insertion or a gene-trap approach were used, the
      expression pattern of the lacZ gene in ES fetuses was identical to that of
      fetuses that were derived from breeding of chimeric mice. Thus, this technique
      can be considered as a useful and rapid approach to produce fetuses and mice
      directly from ES cells carrying predetermined genetic changes and offers many
      applications for studies in molecular genetics and developmental biology.

PMID- 9152007
TI  - Expression and regulation of a netrin homologue in the zebrafish embryo.
AB  - Proteins of the Netrin family have been implicated in axon guidance in both C.
      elegans and vertebrates. Here, we report the cloning and expression analysis of a
      zebrafish netrin homologue (net1). net1 is expressed in the floor plate and the
      anterior ventral neural tube. Its expression is ectopically induced by
      misexpression of sonic hedgehog (shh) and a dominant negative mutant of the
      regulatory subunit of protein kinase A (dnReg). Ectopic activation of net1,
      however, is restricted to distinct regions in the brain. Upon overexpression of
      shh or dnReg in cyclops mutants, which have strongly impaired net1 expression in
      the ventral neural tube, rescue of net1 expression was observed in the brain but
      not in the spinal cord. Ectopic expression of dnReg and Shh protein can be
      detected at high levels throughout injected embryos from pre-gastrula stages
      onwards suggesting that the competence of the neural plate to respond to Shh
      signalling activity differs regionally. Similar to net1, axial, the zebrafish
      homologue of mammalian HNF3beta, which is also expressed along the ventral neural
      tube, is ectopically induced in the brain of embryos injected with dnReg mRNA.
      Neurons differentiate normally within domains of ectopic net1 and axial
      expression. Thus, dorsal neuronal differentiation appears to be unaffected
      despite co-expression of a gene program specific for the ventral neural tube.
      This also suggests that these ectopically expressing regions have not
      differentiated into floor plate.

PMID- 9152008
TI  - Functional expression of rat synapse-associated proteins SAP97 and SAP102 in
      Drosophila dlg-1 mutants: effects on tumor suppression and synaptic bouton
      structure.
AB  - The synapse-associated proteins SAP97 and SAP102 are mammalian proteins that are
      structurally related to the Drosophila tumor suppressor protein DlgA. Previous
      analyses revealed that DlgA is essential for the integrity of epithelia and
      neuromuscular synapses. Here we show that synaptic bouton structure is severely
      affected in mutant larvae carrying the dlg-1(XI-2) allele. We have tested SAP97
      and SAP102 for functional homology to DlgA by heterologous expression in
      Drosophila. Both SAP97 and SAP102 can suppress tumor formation in dlg-1 mutant
      flies and mimic DlgA at larval neuromuscular junctions. Neuronal expression of
      SAP97 or SAP102 is required for morphological restoration of synaptic boutons,
      indicating that presynaptic DlgA function is essential for establishing
      structurally intact motor nerve terminals at larval neuromuscular junctions.

PMID- 9152010
TI  - A graded response to BMP-4 spatially coordinates patterning of the mesoderm and
      ectoderm in the zebrafish.
AB  - The effects of signal perturbation on expression domains of molecular markers for
      the mesoderm and ectoderm have been analysed across the dorso-ventral axis in
      zebrafish embryos. Injection of RNA encoding bone morphogenetic protein-4 (BMP-4)
      ventralised the embryo, expanding the intermediate mesoderm and non-neural
      ectoderm at the expense of the dorso-anterior mesoderm and neural plate. A dose
      dependent response was observed both morphologically and in expression of gta3,
      MyoD and pax2. Conversely, increases in dorso-anterior mesoderm and neurectoderm
      were generated by injection of RNA encoding either a dominant-negative BMP
      receptor (delta BMPR) or noggin, as demonstrated by goosecoid and pax2
      expression. Ventral BMP-4 expression was also inhibited. Thus, patterning of both
      the mesoderm and the ectoderm during gastrulation appears to depend, directly or
      indirectly, on the level of BMP activity. Consistent with their locations prior
      to formation of the neural tube, elevated BMP-4 increased the number of dorsal
      spinal cord neurons whilst sonic hedgehog and islet1 expression in the ventral
      spinal cord were reduced. However, the ectopic neurons were not positioned more
      ventrally, implicating a prepattern in the dorsal neural tube that is independent
      of the ventral central nervous system.

PMID- 9152009
TI  - Evidence for genetic control of Sonic hedgehog by Gli3 in mouse limb development.
AB  - Sonic hedgehog (Shh) expression in the developing limb is associated with the
      zone of polarising activity (ZPA), and both are restricted to the posterior part
      of the limb bud. We show that the expression patterns of Shh and Gli3, a member
      of the Gli-family believed to function in transcriptional control, appear to be
      mutually exclusive in limb buds of mouse embryos. In the polydactyly mouse mutant
      extra toes (Xt), possessing a null mutation of Gli3, Shh is additionally
      expressed in the anterior region of the limb bud. The transcript of Ptc, the
      putative receptor for Shh protein, can be detected anteriorly as well. Other
      genes known to be involved in limb outgrowth and patterning, like Fibroblast
      growth factor (Fgf), Bone morphogenetic protein (Bmp), and Hoxd are misexpressed
      in relation to the ectopic Shh expression domain in Xt limb buds. This data
      suggest that Gli3 is a regulator of Shh expression in mouse limb development.

PMID- 9152012
TI  - Cell-lineage and clonal-contribution map of the trochophore larva of Patella
      vulgata (mollusca).
AB  - Molluscan development is characterised by its extremely regular cleavage pattern.
      In numerous molluscs the fate of various early-cleavage stage blastomeres has
      been determined and fate maps have been constructed. On the basis of similarities
      between these fate maps, a generalised molluscan cell-lineage map has been
      constructed. Recently, the validity of this map has been challenged. In this
      study, the cell-lineage of the first-, second-, and third-quartet micromeres and
      third-generation macromeres of the equally-cleaving gastropod mollusc Patella
      vulgata was studied by fluorescent cell-lineage tracer injection followed by
      epifluorescence microscopy and confocal laser scanning microscopy. For the first
      time, a complete cell-lineage map, in the form of a clonal-contribution map of
      the trochophore, has been constructed with the use of fluorescent cell-lineage
      tracers. This map both agrees and differs in a number of respects with the
      generalised cell-lineage map of molluscs. The most important deviation is that
      the micromere 2d, formerly referred to as the first somatoblast, is not the only
      cell that forms the foot and shell gland in Patella.

PMID- 9152011
TI  - Winged-helix, Hedgehog and Bmp genes are differentially expressed in distinct
      cell layers of the murine yolk sac.
AB  - The visceral yolk sac plays a critical role in normal embryogenesis, yet little
      is known about the specific molecules that regulate its development. We show here
      that four winged-helix genes (HNF-3alpha, HNF-3beta, HNF-3gamma and HFH-4) are
      restricted to visceral endoderm. In the absence of HNF-3beta, visceral endoderm
      forms but the morphogenetic movements by which the embryo becomes enclosed within
      its yolk sac are disrupted and serum protein gene transcription is greatly
      reduced. Hedgehog and Bmp genes, which encode signaling molecules known to play
      multiple roles in embryonic development, are also differentially expressed in the
      closely apposed yolk sac mesoderm and endoderm layers. Our results suggest that
      similar mechanisms may be utilized to mediate inductive interactions in both
      extraembryonic and embryonic tissues.

PMID- 9152013
TI  - Expression of the helix-loop-helix factor, Hes3, during embryo development
      suggests a role in early midbrain-hindbrain patterning.
AB  - The Hes gene family members are mammalian homologues of the Drosophila hairy and
      Enhancer of split genes. hairy and Enhancer of split function in both
      segmentation and in the Notch neurogenic pathway during Drosophila embryo
      development. Previous expression data suggested a conserved role for the Hes
      genes in the Notch signalling pathway, but not in segmentation. Here, Hes3
      expression during mouse embryogenesis is described. During early development of
      the central nervous system, Hes3 is expressed specifically in the region of the
      midbrain/hindbrain boundary, and in rhombomeres 2, 4, 6 and 7. This pattern
      suggests that Hes3 may have a conserved role as a segmentation gene. Later in
      development, Hes3 is co-expressed with other neurogenic gene homologues in the
      developing central nervous system and epithelial cells undergoing mesenchyme
      induction.

PMID- 9152015
TI  - Effect of ethanol pretreatment on mercury distribution in organs of fetal guinea
      pigs following in utero exposure to mercury vapor.
AB  - Ethanol (Et-OH), which is an inhibitor of catalase, reduces oxidation of mercury
      vapor (Hg0) into ionic mercury (Hg2+). Consequently, exposure of pregnant animals
      to Hg0 with pretreatment of Et-OH causes penetration of larger amount of Hg0 to
      the fetus. The fate of Hg0 in the fetus of pregnant guinea pigs, thus penetrated,
      was investigated. Et-OH pretreatment of the dams resulted in the transfer of more
      mercury to the fetuses and led to a marked increase in mercury in the fetal
      liver. Furthermore, according to the mercury distribution in the fetal organs,
      the animals in the Et-OH-pretreated group fell into two subgroups: a group of
      fetuses (subgroup 1) had higher mercury concentrations in the brain, heart and
      kidney compared with the group which was exposed to Hg0 without Et-OH
      pretreatment (Hg0 group) and another group (subgroup 2) with similar organ
      mercury concentrations to that of the Hg0 group. Determination of metallothionein
      (MT) concentrations showed that MT concentration in the fetal liver of subgroup 2
      was significantly higher than that of subgroup 1 and the Hg0 group. Further, the
      Sephadex G-75 chromatography of the cytosol of the fetal liver in subgroup 2
      revealed that most of mercury, about 66%, was bound to metallothionein-like
      protein. On the other hand, in the cytosol of fetal liver of subgroup 1, a small
      amount, about 10% appeared in fractions corresponding to MT. These findings
      suggest that fetal hepatic MT plays a significant defense role against mercury
      crossing the placenta and is involved in regulating for the mercury distribution
      in the fetus.

PMID- 9152014
TI  - Effect of thiols on cadmium-induced expression of metallothionein and other
      oxidant stress genes in rat lung epithelial cells.
AB  - This study examined cadmium-induced alterations in metallothionein-1 (MT),
      glutathione-S-transferase Ya (GST), and heme oxygenase-1 (HO) gene expression in
      an adult rat lung epithelial cell line. Elevations in MT mRNA and HO mRNA
      occurred as early as 1 h after exposure to a sub-toxic concentration of CdCl(2)
      (10 microM) whereas GST expression did not increase significantly until 4 h after
      Cd addition. At t = 8 h, levels of GST, MT, and HO mRNA were elevated 9-fold, 27
      fold, and 44-fold, respectively, over basal expression. By 24 h, MT expression
      was almost back to baseline levels. GST mRNA and HO mRNA were also reduced,
      compared to 8 h, but to a lesser extent than MT expression. The MT gene was more
      responsive to low Cd concentrations (5 microM) than the genes for HO or GST
      whereas HO was induced more than the others at higher Cd doses (10-20 microM).
      Pro-oxidant conditions play a role in Cd-induced gene expression, as suggested by
      the rapid decline (15-30 min) in glutathione (GSH), amounting to 25-30% of
      baseline, that occurred after exposure to 10 microM CdCl(2). This was followed by
      resynthesis of GSH to a concentration higher than the initial. Depleting GSH by
      treatment of cells with buthionine sulfoximine (BSO) enhanced Cd-induced
      expression of MT, GST, and HO whereas thiol supplementation, by treatment with N
      acetyl cysteine (NAC), had an attenuating effect. BSO and NAC pretreatment had no
      effect on basal gene expression or Cd uptake. In summary, this study has shown
      that: (1) Cd increases MT, GST, and HO gene expression in a time- and dose
      dependent fashion: (2) MT gene expression appears to be most sensitive to Cd
      whereas the HO gene is most inducible at higher Cd concentrations; (3) Cd-induced
      expression is enhanced by GSH depletion and suppressed by thiol supplementation.

PMID- 9152016
TI  - Antimony-induced alterations in thiol homeostasis and adenine nucleotide status
      in cultured cardiac myocytes.
AB  - Cultured cardiac myocytes were exposed for up to 4 h to 50 and 100 microM
      potassium antimonyl tartrate (PAT). After 4 h, 50 and 100 microM PAT killed 14
      and 33% respectively of the cardiac myocytes. PAT-induced alterations in both
      protein and nonprotein thiol homeostasis. Transient increases in oxidized
      glutathione disulfide (GSSG) levels were detected after cells were treated with
      100 microM PAT for 2 h. After 4 h, both concentrations of PAT significantly
      depleted reduced glutathione (GSH) levels. Protein thiols levels were also
      decreased after a 2-h exposure to 50 and 100 microM PAT. Cells treated with 50
      microM and 100 microM PAT had a 15% and 40% reduction respectively in protein
      thiols after 4 h. PAT also significantly inhibited glutathione peroxidase and
      pyruvate dehydrogenase activity in cardiac myocytes. Pyruvate dehydrogenase
      activity levels were inhibited as early as 1 h after cells were treated with both
      concentrations of PAT. Cardiac myocyte ATP levels were also decreased by PAT, but
      only after a 4-h exposure to 50 microM and 100 microM PAT. Decreases in cellular
      ATP levels paralleled PAT toxicity put appeared to be secondary to other cellular
      changes initiated by PAT exposure.

PMID- 9152017
TI  - Computational predictive programs (expert systems) in toxicology.
AB  - The increasing number of pollutants in the environment raises the problem of the
      toxicological risk evaluation of these chemicals. Several so called expert
      systems (ES) have been claimed to be able to predict toxicity of certain chemical
      structures. Different approaches are currently used for these ES, based on
      explicit rules derived from the knowledge of human experts that compiled lists of
      toxic moieties for instance in the case of programs called HazardExpert and DEREK
      or relying on statistical approaches, as in the CASE and TOPKAT programs. Here we
      describe and compare these and other intelligent computer programs because of
      their utility in obtaining at least a first rough indication of the potential
      toxic activity of chemicals.

PMID- 9152018
TI  - Immunotoxicological effects of benzene inhalation in male Sprague-Dawley rats.
AB  - The inhalation of benzene is toxic to various components of the immunologic
      system in rodents. Spleen and thymus weights, total spleen and femur marrow cell
      counts, enumeration of spleen B- and T-lymphocytes, and an assessment of humoral
      immunocompetence, were used to evaluate the immunotoxicity of benzene in male
      Sprague-Dawley rats. Rats were exposed to 0, 30, 200 or 400 ppm benzene for 6
      h/day, 5 days/week for 2 or 4 weeks. An early indicator of immunotoxicity was a
      reduction in the number of B-lymphocytes after 2 weeks of 400 ppm. After 4 weeks
      of 400 ppm, there was a reduction in thymus weight and spleen B-, CD4+/CD5+ and
      CD5+ T-lymphocytes. Rats exposed to 30, 200 or 400 ppm benzene for 2 or 4 weeks
      and challenged with sheep red blood cells developed a humoral response comparable
      to that of the control (0 ppm) animals. Enumeration of spleen T- and B
      lymphocytes in rats exposed to benzene and challenged with SRBC showed only a
      transient reduction in spleen B-lymphocytes after 2 weeks of exposure to 400 ppm.
      These data suggest that there are no immunotoxicological effects of exposure to
      200 ppm benzene or less, in rats exposed for 6 h/day, 5 days/week for 2 or 4
      weeks.

PMID- 9152019
TI  - A Drosophila Tpr protein homolog is localized both in the extrachromosomal
      channel network and to nuclear pore complexes.
AB  - Here we report structural, molecular, and biochemical characterizations of Bx34,
      a Drosophila melanogaster nuclear coiled-coil protein which is localized to
      extrachromosomal and extranucleolar spaces in the nuclear interior and which is
      homologous to the mammalian nuclear pore complex protein Tpr. In the nuclear
      interior, Bx34 is excluded from chromosomes and the nucleolus and generally
      localizes to regions between these structures and the nuclear periphery. This
      distribution matches the 'extrachromosomal channel network' described previously.
      In the nuclear periphery, Bx34 localizes on or near nuclear pore complexes.
      Biochemically, Bx34 isolates exclusively with the nuclear matrix fraction. The
      Bx34 cDNA sequence predicts a large protein (262 kDa) with two distinct
      structural domains. The Bx34 N-terminal 70% (180 kDa) is predicted to form an
      extended region of coiled-coil, while the C-terminal 30% (82 kDa) is predicted to
      be unstructured and acidic. Bx34 shows moderate sequence identity over its entire
      length to the mammalian nuclear pore complex protein 'Tpr' (28% amino acid
      identity and 50% similarity). Furthermore, several of the sequence motifs and
      biochemical similarities between Bx34 and Tpr are sufficiently striking that it
      is likely that Bx34 and Tpr are functionally related. The Bx34 gene exists in a
      single copy in region 48C of chromosome 2R. The localization of coiled-coil Bx34
      to both the nuclear interior and nuclear pore complexes and its sequence
      similarity to a known nuclear pore complex protein leads to speculations about a
      role for Bx34 in nucleo-cytoplasmic transport which we can test using molecular
      genetic approaches.

PMID- 9152020
TI  - Mutation of a gene for a Drosophila kinesin-like protein, Klp38B, leads to
      failure of cytokinesis.
AB  - Mutations in a gene (Klp38B) encoding a novel kinesin-like protein in Drosophila
      melanogaster lead to the formation of polyploid cells in the larval central
      nervous system and in the follicle cells of adult egg chambers. Some homozygous
      mutants survive to adulthood and also exhibit morphological defects indicative of
      abnormal cell cycle progression, including rough eyes, missing bristles, and
      abnormal abdominal cuticles. In larval brains, there is no accumulation of
      mitotic cells and the frequency of anaphase figures is comparable to wild type,
      suggesting that nuclear division is not affected. Such brains contain polyploid
      cells with metaphase and anaphase chromosomes associated with bipolar spindles.
      Such spindles have a number of unseparated centrosomes at their poles reflecting
      the degree of polyploidy of the cell. Follicle cells frequently contain two
      nuclei of roughly equal size. Taken together, we conclude that these Klp38B
      mutations lead to a failure of cytokinesis resulting in polyploidy, and discuss
      whether or not this is a direct effect of the mutation.

PMID- 9152021
TI  - Functional analysis of human RPS14 null alleles.
AB  - Previously we described a large collection of cloned human DNAs that encode
      chemically defined missense mutations within the ribosomal protein S14 sequence.
      We determined that biologically inactive (i.e. null) alleles resulted primarily
      from point mutations targeted to two internal segments of the S14-coding sequence
      and designated these functionally critical regions as domains B and D. Further,
      we inferred that structural determinants within domains B and D are required for
      proper incorporation of the S14 protein into nascent 40 S ribosomal particles
      and/or for the normal function of mature cytoplasmic ribosomes. In this study we
      have used immunofluorescence to monitor the intracellular trafficking of
      epitopically labeled human S14 protein isoforms transiently expressed by cultured
      Chinese hamster cells. Data obtained distinguish null alleles of RPS14 which
      encode proteins that are not incorporated into pre-ribosomal subunit particles
      from null alleles whose products are compatible with normal ribosome assembly
      processes but result in functionally inactive cytoplasmic 40 S ribosomal
      subunits. Mutations assigned to the first allele class involve amino acid
      replacements located within S14 domains B and D; whereas mutations assigned to
      the second class are distributed throughout the S14 protein-coding sequence.

PMID- 9152022
TI  - Contrasting effects of K8 and K18 on stabilizing K19 expression, cell motility
      and tumorigenicity in the BSp73 adenocarcinoma.
AB  - The co-expression of vimentin and keratin-type intermediate filaments in the same
      cell was often reported to correlate with increased invasiveness and a more
      aggressive tumorigenic phenotype. To address the possible physiological relevance
      of these observations, we transfected simple keratins (K8 and 18) either
      individually, or in combination, into a tumorigenic but non-metastatic pancreatic
      adenocarcinoma that expresses vimentin but no keratins. Expression of K8 resulted
      in the stabilization of endogenous K19 in these cells, and formation of keratin
      filaments containing K8 and K19. Transfection of K18 yielded unstable K18
      protein, but K18 could be stabilized when K8 was co-expressed in the same cells.
      Clones expressing K18 alone, or together with K8, displayed a reduced ability to
      grow in soft agar and decreased motility when compared to control, or K8/19
      expressing cells. Moreover, K18 expressing cells were dramatically inhibited in
      their ability to form tumors when injected into syngeneic animals. The extent of
      suppression in the tumorigenicity of these cells correlated with the level of K18
      expressed by these cells. The results show that K18 expression in cells may
      result in the suppression of the motile and tumorigenic abilities of this
      adenocarcinoma.

PMID- 9152023
TI  - Imaging of Ca2+ transients induced in Paramecium cells by a polyamine
      secretagogue.
AB  - In Paramecium tetraurelia cells analysis of transient changes in Ca2+
      concentration, [Ca2+]i, during aminoethyldextran (AED) stimulated synchronous (<1
      second) trichocyst exocytosis has been hampered by various technical problems
      which we now have overcome. While Fura Red was found appropriate for quantitative
      double wavelength recordings, Fluo-3 allowed to follow, semi-quantitatively but
      with high time resolution, [Ca2+]i changes by rapid confocal laser scanning
      microscopy (CLSM). Resting values are between 50 and 70 nM in the strains
      analysed (7S wild type, as well as a non-discharge and a trichocyst-free mutant,
      nd9-28 degrees C and tl). In all strains [Ca2+]i first increases at the site of
      AED application, up to 10-fold above basal values, followed by a spillover into
      deeper cell regions. This might: (i) allow a vigorous Ca2+ flush during
      activation, and subsequently (ii) facilitate re-establishment of Ca2+ homeostasis
      within > or =20 seconds. Because of cell dislocation during vigorous trichocyst
      exocytosis, 7S cells could be reasonably analysed only by CLSM after Fluo-3
      injection. In 7S cells cortical [Ca2+]i transients are strictly parallelled by
      trichocyst exocytosis, i.e. in the subsecond time range and precisely at the site
      of AED application. Injection of Ca2+ is a much less efficient trigger for
      exocytosis. Ca2+-buffer injections suggest a requirement of [Ca2+]i >1 to 10
      microM for exocytosis to occur in response to AED. In conclusion, our data
      indicate: (i) correlation of cortical [Ca2+]i transients with exocytosis, as well
      as (ii) occurrence of a similar signal transduction mechanism in mutant cells
      where target structures may be defective or absent.

PMID- 9152024
TI  - Activation of the beta2 integrin Mac-1 (CD11b/CD18) by an endogenous lipid
      mediator of human neutrophils and HL-60 cells.
AB  - beta2 integrins (CD11/CD18) play a key role in the adhesion, activation,
      migration and phagocytosis of human neutrophils. In order to exert their
      functions, beta2 integrins require activation, which results in an enhancement of
      ligand affinity. This functional up-regulation is probably due to a
      conformational change of the beta2 integrins, but the mechanisms of inside-out
      signaling that trigger this activation are still under investigation. In the
      present study, the effect of cellular lipids on the affinity state of beta2
      integrins was investigated. Lipids were extracted from human neutrophils and HL
      60 cells after stimulation with IL-8 or phorbol ester, respectively. The extracts
      were purified by anion exchange chromatography and/or HPLC fractionation. The
      lipid extracts induced the adhesion of neutrophils to fibrinogen and, in a cell
      free assay system, the binding of C3bi-coated zymosan-particles by purified beta2
      integrin Mac-1 (CD11b/CD18). The integrin up-regulating activity was resistant to
      ester hydrolysis, eluted as one particular HPLC-fraction, and showed an
      absorption maximum at 194+/-2 nm. Taken together, these data support the concept
      that activated neutrophils and HL-60 cells can generate an endogenous lipid
      mediator, which up-regulates ligand binding activity of beta2 integrins.

PMID- 9152025
TI  - Sec12p requires Rer1p for sorting to coatomer (COPI)-coated vesicles and
      retrieval to the ER.
AB  - In Saccharomyces cerevisiae cells lacking the Rer1 protein (Rer1p), the type II
      transmembrane protein Sec12p fails to be retained in the ER. The transmembrane
      domain of Sec12p is sufficient to confer Rer1p-dependent ER retention to other
      membrane proteins. In rer1 mutants a large part of the Sec12-derived proteins can
      escape to the late Golgi. In contrast, rer3 mutants accumulate Sec12-derived
      hybrid proteins carrying early Golgi modifications. We found that rer3 mutants
      harbour unique alleles of the alpha-COP-encoding RET1 gene. ret1 mutants, along
      with other coatomer mutants, fail to retrieve KKXX-tagged type I transmembrane
      proteins from the Golgi back to the ER. Surprisingly rer3-11(=ret1-12) mutants do
      not affect this kind of ER recycling. Pulse-chase experiments using these mutants
      show that alpha-COP and Rer1p function together in a very early Golgi compartment
      to initiate the recycling of Sec12p-derived hybrid proteins. Rer1p protein may be
      directly involved in the retrieval process since it also recycles between the
      early Golgi and ER in a coatomer (COPI)-dependent manner. Rer1p may act as an
      adapter coupling the recycling of non-KKXX transmembrane proteins like Sec12p to
      the coatomer (COPI)-mediated backward traffic.

PMID- 9152026
TI  - Localization of a novel 210 kDa protein in Xenopus tight junctions.
AB  - The tight junction is the most apical member of the intercellular junctional
      complex. It functions as a permeability barrier between epithelial cells and
      maintains the integrity of the apical and basolateral membrane domains. In order
      to study tight junctions in Xenopus laevis, a polyclonal antibody was raised
      which recognized Xenopus ZO-1. Monoclonal antibody 19B1 (mAb 19B1) was generated
      in rats using a crude membrane preparation from Xenopus lung as antigen. mAb 19B1
      gave immunofluorescent staining patterns identical to those seen with anti-ZO-1
      on monolayers of Xenopus A6 kidney epithelial cells and on frozen sections of
      Xenopus kidney, liver, and embryos. Electron microscopy showed that the 19B1
      antigen colocalized with ZO-1 at the tight junction. Western blotting and
      immunoprecipitation demonstrated that ZO-1 is an approximately 220 kDa protein in
      Xenopus, while mAb 19B1 identified an approximately 210 kDa antigen on
      immunoblots. Immunoprecipitates of ZO-1 were not recognized by mAb 19B1 by
      western analysis. The solubility properties of the 19B1 antigen suggested that it
      is a peripheral membrane protein. Thus, the antigen recognized by the new
      monoclonal antibody 19B1 is not ZO-1 and represents a different Xenopus tight
      junction associated protein.

PMID- 9152028
TI  - The carboxy-terminal peptides of 46 kDa and 300 kDa mannose 6-phosphate receptors
      share partial sequence homology and contain information for sorting in the early
      endosomal pathway.
AB  - Recycling of mannose 6-phosphate receptors was investigated by microinjection of
      F(ab) fragments against their carboxy-terminal peptides (residues 54-67 or 150
      164 of the cytoplasmic domain of 46 kDa and 300 kDa mannose 6-phosphate receptor,
      respectively). For each receptor, masking the carboxy-terminal peptide by the
      corresponding F(ab) fragments resulted in complete depletion of the intracellular
      pool. Redistributed 300 kDa mannose 6-phosphate receptor was shown to accumulate
      at the plasma membrane and to internalize anti-ectodomain antibodies.
      Internalization of anti-ectodomain antibodies was also observed for redistributed
      46 kDa mannose 6-phosphate receptor. Semiquantitative analysis suggested that for
      both redistributed receptors the amount of intracellularly accumulated anti
      ectodomain antibodies was reduced. In addition, downstream transport along the
      endosomal pathway was slowed down. These data suggest that sorting information
      for early steps in the endocytic pathway is contained within the carboxy-terminal
      peptides of mannose 6-phosphate receptors.

PMID- 9152027
TI  - Characterization of the interactions of alpha-catenin with alpha-actinin and beta
      catenin/plakoglobin.
AB  - Cadherins are calcium-dependent, cell surface glycoproteins involved in cell-cell
      adhesion. To function in cell-cell adhesion, the transmembrane cadherin molecule
      must be associated with the cytoskeleton via cytoplasmic proteins known as
      catenins. Three catenins, alpha-catenin, beta-catenin and gamma-catenin (also
      known as plakoglobin), have been identified. beta-catenin or plakoglobin is
      associated directly with the cadherin; alpha-catenin binds to beta
      catenin/plakoglobin and serves to link the cadherin/catenin complex to the actin
      cytoskeleton. The domains on the cadherin and betacatenin/plakoglobin that are
      responsible for protein-protein interactions have been mapped. However, little is
      known about the molecular interactions between alpha-catenin and beta
      catenin/plakoglobin or about the interactions between alpha-catenin and the
      cytoskeleton. In this study we have used the yeast two-hybrid system to map the
      domains on alpha-catenin that allow it to associate with beta-catenin/plakoglobin
      and with alpha-actinin. We also identify a region on alpha-actinin that is
      responsible for its interaction with alpha-catenin. The yeast two-hybrid data
      were confirmed with biochemical studies.

PMID- 9152029
TI  - The search for an effective malaria vaccine.

PMID- 9152030
TI  - Moraxella (Branhamella) catarrhalis--clinical and molecular aspects of a
      rediscovered pathogen.
AB  - Since its discovery at the end of the nineteenth century, Moraxella (Branhamella)
      catarrhalis has undergone several changes of nomenclature and periodic changes in
      its perceived status as either a commensal or a pathogen. Molecular analysis
      based on DNA hybridisation or 16S rDNA sequence comparisons has established its
      phylogenetic position as a member of the Moraxellaceae and shown that it is
      related more closely to Acinetobacter spp. than to the genus Neisseria in which
      it was placed formerly. However, confusion with phenotypically similar Neisseria
      spp. can occur in the routine diagnostic laboratory if appropriate identification
      tests are not performed. M. catarrhalis is now accepted as the third commonest
      pathogen of the respiratory tract after Streptococcus pneumoniae and Haemophilus
      influenzae. It is a significant cause of otitis media and sinusitis in children
      and of lower respiratory tract infections in adults, especially those with
      underlying chest disease. Nosocomial spread of infection, especially within
      respiratory wards, has been reported. Invasive infection is uncommon, but
      analysis of reports for England and Wales between 1992 and 1995 revealed 89 cases
      of M. catarrhalis bacteraemia, with the peak incidence in children aged 1-2
      years. Carriage rates of M. catarrhalis are high in children and in the elderly,
      but its role as a commensal organism has probably been overstated in the past.
      Approximately 90% of strains are now beta-lactamase positive and, given that the
      first such strain was reported in 1976, this represents a dramatic increase in
      frequency over the last 20 years which has not been paralleled in any other
      species. The BRO-1 and BRO-2 beta-lactamase enzymes of M. catarrhalis are found
      in other Moraxellaceae, but are not related to beta-lactamases of any other
      species and their origin is therefore unknown. Molecular and typing studies have
      shown that the M. catarrhalis species is genetically heterogeneous and these
      methods have aided epidemiological investigation. Studies of factors that may be
      related to pathogenicity have shown the existence of three serotypes of
      lipooligosaccharide and the presence of fimbriae and a possible capsule. Some
      strains are serum-resistant, probably by virtue of interference with complement
      action, whilst transferrin- and lactoferrin-binding proteins enable the organism
      to obtain iron from its environment. An antibody response in humans to various M.
      catarrhalis antigens, including highly conserved outer-membrane proteins, has
      been demonstrated. Increased understanding of the organism's pathogenic
      properties and the host response to it may help to identify suitable vaccine
      targets or lead to other strategies to prevent infection. Whilst it remains, at
      present, the third most important respiratory pathogen, the impact of
      immunisation strategies for other organisms may change this position. The speed
      with which M. catarrhalis acquired beta-lactamase demonstrates the capacity of
      this organism to surprise us.

PMID- 9152032
TI  - Epidemiological analysis of strains of Salmonella enterica serotype Enteritidis
      from foodborne outbreaks occurring in Italy, 1980-1994.
AB  - Polymerase chain reaction (PCR-) ribotyping was performed on 243 strains of
      Salmonella enterica serotype Enteritidis isolated during the years 1980-1994 from
      58 foodborne outbreaks occurring in different regions of Italy. The majority (37)
      of the outbreaks were attributed to phage type (PT) 4, followed by PT1 (seven
      outbreaks); the latter was identified in 1993 in Italy in epidemic strains of
      Enteritidis. In eight cases more than one phage type was recognised from a single
      event. Nine PCR-ribotypes (PCR-RTs) were detected, with a strong prevalence of
      PCR-RTs f7 and e5 (23 and 21 outbreaks, respectively). In two instances two
      distinct PCR-RTs were identified within strains from a single outbreak. All but
      one of the PT1 outbreaks were caused by PCR-RT f7, whereas PT4 outbreaks could be
      subdivided into six subsets. Clustering of isolates was consistent with data
      obtained from epidemiological investigations. PCR-ribotyping proved to be an
      effective and reliable tool for subtyping isolates of Enteritidis belonging to
      the most frequent phage types. Nevertheless, in terms of laboratory expertise and
      lack of inter-laboratory standardisation, this typing technique is best suited
      for reference laboratories.

PMID- 9152031
TI  - Failure to isolate Helicobacter pylori from stray cats indicates that H. pylori
      in cats may be an anthroponosis--an animal infection with a human pathogen.
AB  - The recent isolation of Helicobacter pylori from cats obtained from a commercial
      supplier has potentially important public health implications. The present study
      investigated whether H. pylori infection was common in stray cats. Twenty-five
      cats were examined for the presence of H. pylori by histological examination,
      culture and two polymerase chain reaction (PCR) assays. Histologically, the
      gastric biopsy specimens from all cats showed large spiral organisms typical of
      H. felis and not H. pylori. Samples from 23 cats yielded bacterial growth and two
      had no growth. Colonies grossly similar to H. pylori were tested for catalase,
      oxidase, urease and Gram's stain reactions. None was H. pylori. All samples
      tested as positive by the Helicobacter 16S rRNA genus-specific PCR assay and only
      six cats and a mouse stomach infected with H. heilmannii gave positive results
      with the adhesin subunit A (hpaA)-specific PCR assay, which is consistent with
      either H. pylori or H. heilmannii. The helicobacters identified in these samples
      by PCR were not cultivable and hence were probably H. heilmannii. H. pylori
      infection is uncommon in stray cats and owning pet cats should not be a threat to
      public health in relation to H. pylori infection.

PMID- 9152033
TI  - Analysis of Neisseria gonorrhoeae in Ontario, Canada, with decreased
      susceptibility to quinolones by pulsed-field gel electrophoresis, auxotyping,
      serotyping and plasmid content.
AB  - The incidence of Neisseria gonorrhoeae with reduced susceptibility to quinolones
      increased from 0.18% (63 of 3285) in 1992 to 0.56% (15 of 2663) in 1993 and 0.62%
      (46 of 2846) in 1994. In all, 65 of the 67 isolates of Neisseria gonorrhoeae with
      decreased susceptibility to quinolones were characterised by pulsed-field gel
      electrophoresis (PFGE), auxotyping, serotyping and plasmid content. The strains
      were distributed among 14 auxotype/serovar (A/S) classes. Thirty isolates (46.2%)
      which were penicillin-susceptible with ciprofloxacin MIC90 of 0.12 mg/L and
      norfloxacin MIC90 of 1.0 mg/L belonged to a single A/S class, OUHL/IA-2. All but
      two of the 30 isolates had identical PFGE restriction profiles with NheI
      restriction endonuclease. Fifteen isolates (23.1%) with MICs in the intermediate
      (or resistant) categories for penicillin and with ciprofloxacin and norfloxacin
      MIC90 of 0.25 and 4.0 mg/L and (0.5 and 4.0 mg/L) respectively, belonged to A/S
      class P/IB-1. The 15 isolates showed nine different patterns with NheI and eight
      patterns with SpeI restriction endonucleases. Two of three beta-lactamase
      producing (PPNG) isolates belonged to A/S class P/IB-5 and had a dissimilar PFGE
      restriction profile with NheI endonuclease; the other isolate belonged to A/S
      class P/IB-8. The remaining 17 isolates were distributed among 11 A/S classes.
      Three isolates within the common A/S class NR/IB-1 were subdivided into two types
      by PFGE as were three isolates belonging to A/S class NR/IB-2. Overall the 65
      isolates of N. gonorrhoeae were distributed into 30 NheI and 26 SpeI
      macrorestriction profiles. All but one isolate harboured the 2.6-MDa cryptic
      plasmid and 18 isolates carried the 24.5-MDa transferable plasmid. The three PPNG
      isolates carried the 4.5-MDa Asian beta-lactamase-producing plasmid and a 25.2
      MDa conjugative plasmid was found in the two TRNG isolates.

PMID- 9152034
TI  - Induction of ulceration and severe gastritis in Mongolian gerbil by Helicobacter
      pylori infection.
AB  - Specific pathogen-free Mongolian gerbils were infected orally with Helicobacter
      pylori to establish a new small animal model of severe gastritis H. pylori was
      recovered by culture from both antrum and body over a 16-week period after a
      single inoculation. The number of H. pylori colonising the antrum was about 100
      fold higher than in the body, and this was consistent throughout the experiment.
      Histological examination showed that all animals developed severe inflammation
      with infiltration of polymorphonuclear leucocytes and mononuclear cells into the
      lamina propria and submucosa of the antrum from 4 weeks after infection. From 8
      weeks after infection, multifocal lymphoid follicles appeared in the lamina
      propria and submucosa, and micro-erosions were also observed in the epithelial
      layer. At 16 weeks after infection, ulceration with disruption of the lamina
      muscularis mucosae was observed in the antral mucosa. To determine whether H.
      pylori caused gastritis or not, infected gerbils were treated with amoxycillin.
      After the treatment, gastritis could not be seen in the gastric mucosa.
      Therefore, the Mongolian gerbil is a useful small animal model to study the
      pathogenesis of H. pylori in gastric ulceration and severe gastritis and to
      assess anti-H. pylori treatment.

PMID- 9152035
TI  - Detection of Vibrio cholerae and V. mimicus heat-stable toxin gene sequence by
      PCR.
AB  - Previously the heat-stable enterotoxin in Vibrio cholerae and V. mimicus has been
      detected by suckling mouse assay, a non-specific approach, and by DNA probes, a
      time-consuming method. This report describes a polymerase chain reaction (PCR)
      procedure for the detection of the stn (NAG-ST) and sto (O1-ST) gene sequences
      that is rapid and specific, allowing toxin gene molecular characterisation. A
      total of 34 V. cholerae and V. mimicus isolates was examined for ST and CT genes.
      The NAG-ST gene sequence was amplified in 13 of 22 non-O1/non-O139 V. cholerae
      and three of five V. mimicus strains. A new enterotoxin gene sequence pattern was
      found with MseI and TaqI restriction endonuclease PCR fragment digestion of two
      V. cholerae isolates, in addition to the pattern anticipated from the Genbank
      sequence, and found with the other ST+. These results show that ST-PCR detection
      is useful for the characterisation of V. cholerae and V. mimicus.

PMID- 9152036
TI  - Role of type-1 fimbriae in the pathogenesis of chronic pyelonephritis in relation
      to reactive oxygen species.
AB  - The role of type-1 fimbriae in the pathogenesis of chronic pyelonephritis was
      studied for two Escherichia coli strains. Although both strains produced a
      similar total oxidative burst of chemiluminescence in macrophages from uninfected
      mice, the extracellular oxidative burst was greater with the non-fimbriate mutant
      E. coli BH-5 than its type-1 fimbriate parent E. coli 31-B. Moreover, macrophages
      from mice infected with the non-fimbriate mutant gave a much greater oxidative
      burst when stimulated with latex particles than that given by macrophages from
      mice infected with the type-1 fimbriate parent. These results correlated with the
      degree of renal inflammation and scarring as measured by malondialdehyde
      formation. Hence, the role of type-1 fimbriae in the pathogenesis of chronic UTI
      although documented does not appear to be significant.

PMID- 9152037
TI  - The ability of a Proteus mirabilis strain to invade the bloodstream is
      independent of its proticine production/proticine sensitivity type.
AB  - Proteus mirabilis strains frequently infect the upper urinary tract and some
      progress to invade the bloodstream. In an attempt to determine if these were
      features only of particular strains of P. mirabilis, isolates from the blood of
      38 unrelated patients, many of whom had an underlying urinary tract infection,
      and eight from different sources and sites within the upper urinary tract, were
      analysed by proticine production/proticine sensitivity (p/s) typing. Twenty-six
      different p/s types were found among the 38 isolates from blood and seven among
      the eight isolates from the upper urinary tract. The p/s types found previously
      to be associated frequently with virulence for the upper urinary tract were not
      found. Analyses of the frequency of occurrence of the different p/s types and of
      their distribution showed no evidence that the p/s characteristics of a P.
      mirabilis strain conferred any advantage on its ability to infect the upper
      urinary tract or invade the bloodstream.

PMID- 9152038
TI  - Detection of Ureaplasma urealyticum in urine of patients with systemic lupus
      erythematosus and healthy individuals by culture and polymerase chain reaction.
AB  - A method was developed to detect Ureaplasma urealyticum in urine by the
      polymerase chain reaction (PCR). A 457-bp fragment of the urease gene of U.
      urealyticum was amplified by PCR. Before PCR, components disturbing the
      amplification had to be reduced. This was possible by diluting the urine 1 in 10
      with distilled water and by the extraction of the U. urealyticum DNA. Urine
      specimens from 41 patients with systemic lupus erythematosus (SLE) and 21 healthy
      individuals were treated by the dilution method and investigated by PCR for U.
      urealyticum DNA. The results were compared with those obtained by culture and the
      detection rates of PCR and culture were found to be identical. Also there was no
      difference in the detection rates of U. urealyticum from urine of SLE patients
      and healthy individuals; 10 (24.4%) of the 41 urine specimens from SLE patients
      and five (23.8%) of the 21 urine specimens from healthy individuals gave positive
      results for U. urealyticum. The results of this study do not indicate a decisive
      role for U. urealyticum in SLE.

PMID- 9152039
TI  - Widely used, commercially available Chlamydia pneumoniae antigen contaminated
      with mycoplasma.
AB  - Mycoplasma contamination was detected in a widely used commercially available
      Chlamydia pneumoniae antigen preparation. Contamination was studied with a
      mycoplasma group-specific 16S rRNA polymerase chain reaction (PCR) and sequence
      analysis. Several lots of the purified C. pneumoniae antigen from the Washington
      Research Foundation appeared to be contaminated with the same Mycoplasma species,
      which appeared to be closely related to M. arginini. Antigen slides prepared for
      the detection of chlamydia antibodies by MRL Diagnostics were contaminated with
      the same Mycoplasma sp. Chlamydia antigen slides from Labsystems OY and two
      chlamydia complement fixation reagents (Virion International Distribution Ltd and
      Behring Werke) were not contaminated. It is concluded that commercially available
      C. pneumoniae antigens may contain mycoplasma antigens as well. Although the
      impact of such mycoplasma contamination on the results of chlamydia serology may
      not be significant, routine screening of all antigen preparations obtained by
      tissue culture before their distribution and use is recommended.

PMID- 9152040
TI  - Susceptibilities of Actinobacillus actinomycetemcomitans biofilms to oral
      antiseptics.
AB  - The susceptibilities of Actinobacillus actinomycetemcomitans cultures, grown as 1
      or 3-day-old biofilms or as planktonic suspensions, to concentrations of
      chlorhexidine digluconate, cetylpyridinium chloride or triclosan used in
      commercial mouthwashes were compared. Three-day biofilms were the most resistant
      form of the organism and chlorhexidine was the most active antiseptic. Comparison
      of solutions of the pure antibacterial agent with commercial products containing
      the same concentration of antiseptic showed little difference in in-vitro
      activities. The results emphasise that the testing of antimicrobial mouthwashes
      should be performed on bacteria grown as biofilms.

PMID- 9152041
TI  - Microbiology of chronic maxillary sinusitis: comparison between specimens
      obtained by sinus endoscopy and by surgical drainage.
AB  - The aerobic and anaerobic microbiology of sinus aspirates obtained during surgery
      was compared with culture of samples obtained by endoscopy. Six patients with
      chronic maxillary sinusitis were evaluated. Polymicrobial flora was found in all
      specimens (two-to-five isolates/sample). A total of 24 isolates (18 anaerobic,
      five aerobic and one micro-aerophilic) was obtained from sinus aspirates, and 25
      isolates (16 anaerobic and nine aerobic) were found in endoscopic specimens. The
      predominant organisms were Prevotella spp., Fusobacterium nucleatum,
      Peptostreptococcus spp. and Staphylococcus spp. Concordance in the type and
      concentration of organisms was found in all cases. Sixteen of the 18 anaerobes
      isolated from sinus aspirates were also found in the concomitant endoscopic
      sample. Five aerobic isolates were found in both sinus aspirates and endoscopic
      samples and their concentration was similar. However, four aerobic gram-positive
      bacteria (<10(4) cfu/sample) were found only in endoscopy samples. This pilot
      study demonstrates the usefulness of endoscopic aspiration in the isolation of
      bacteria from chronically infected maxillary sinuses.

PMID- 9152042
TI  - Bursting firing of action potentials in central snail neurons elicited by d
      amphetamine: role of cytoplasmic second messengers.
AB  - The role of the intracellular second messengers on the bursting firing of action
      potentials in central snail neurons elicited by d-amphetamine was studied in the
      identified RP4 neuron of the African snail Achatina fulica Ferussac. Oscillation
      of membrane potential and bursting firing of action potentials were elicited by d
      amphetamine in a concentration dependent manner. The bursting firing of action
      potentials was decreased following extracellular application of (1) H8 (N-(2
      methyl-amino) ethyl-3-isoquinoline sulphonamide dihydrochloride), a specific
      protein kinase A inhibitor and (2) anisomycin, a protein synthesis inhibitor.
      However, the bursting firing of action potentials were not affected after (1)
      extracellular application of H7 (1,(5-isoquinoline-sulphonyl)-2-methylpiperasine
      dihydrochloride), a specific protein kinase C (PKC) inhibitor, or (2)
      intracellular application of GDPbetaS, a G protein inhibitor. The oscillation of
      membrane potential of the bursting activity was blocked after intracellular
      injection of 3'-deoxyadenosine, an adenylyl-cyclase inhibitor. These results
      suggested that the bursting firing of action potentials elicited by d-amphetamine
      in snail neurons may be associated with the cyclic adenosine monophosphate (cAMP)
      second messenger system: on the other hand it may not be associated with the G
      protein and protein kinase C activity.

PMID- 9152043
TI  - Localization of dopamine receptors and associated mRNA in transplants of human
      fetal striatal tissue in rodents with experimental Huntington's disease.
AB  - Huntington's Disease (HD) is characterized by deficits in motor and cognitive
      functions. This neurodegenerative disease shows an extensive loss of medium-sized
      spiny projection neurons (GABAergic) within the neostriatum. With the loss of
      these neurons, there is a concomitant loss of associated receptors, such as those
      for GABA, glutamate, and dopamine. In the present study, we have addressed the
      question of whether dopamine receptors are re-established in the lesioned rodent
      striatum following the transplantation of human striatal cells. Human striatal
      cell suspension or saline (transplant controls) was injected into the striatum of
      rats previously lesioned with quinolinic acid (QA). Three nine months following
      transplantation, the animals were sacrificed and the brains were processed for
      receptor autoradiography and in situ hybridization of dopamine D1 and D2 receptor
      subtypes. Our results demonstrate that animals transplanted with human striatal
      cells show a significant increase in D1 receptors following transplantation when
      compared to the lesion area in control animals, while D1 receptor mRNA remains
      unchanged. In contrast to D1 receptor binding, D2 receptor levels are not
      increased in the lesioned and transplanted area of the striatum when compared to
      controls; however, D2 receptor mRNA levels are significantly increased. These
      results demonstrate that at the times the animals were examined, D1 and D2
      receptors were differentially regulated. Our results further indicate that human
      striatal primordium will survive following transplantation and will express D1
      receptors and D2 receptor mRNA that are depleted in the QA lesioned rodent
      striatum. This study compliments and extends previous findings on human striatal
      cell transplantation in rodent models of HD.

PMID- 9152044
TI  - Macrophages/microglia as 'sensors' of injury in the pineal gland of rats
      following a non-penetrative blast.
AB  - The pineal gland of adult rats was examined immunohistochemically and electron
      microscopically following exposure of the animals to a single blast equivalent to
      110 kg TNT explosive. The most dramatic feature in rats killed at 7, 14 and 21
      days after the blast was the upsurge of a large number of macrophages/microglia
      intensely immunostained with OX-42, OX-18, OX-6 and ED1 antibodies. These
      antibodies recognise the complement type three (CR3) receptors, major
      histocompatibility complex class I and class II (MHC I and MHC II) antigens and
      monocyte/macrophage antigens. Cell counts in OX-42 immunostained sections showed
      a two-fold increase at these intervals but returned to normal values at 28 days.
      The immunolabelled cells appeared extremely hypertrophic after the blast when
      compared with those in normal rats. In the latter and in rats killed at 28 days
      after the blast, immunoreactive cells were sparsely distributed. Ultrastructural
      study confirmed a wider occurrence of perivascular macrophages/microglia after
      the blast and the cells were laden with massive amounts of phagosomes resembling
      degenerating pinealocyte processes. It is concluded that the seemingly quiescent
      macrophages/microglia present normally in pineal gland were activated by the
      external blast force. The induced changes including the increase in cell numbers
      and endocytosis, however, were reversible in longer surviving animals.

PMID- 9152045
TI  - Oxidative stress affects the selective ion permeability of voltage-sensitive Ca2+
      channels in cultured retinal cells.
AB  - The effect of ascorbate/Fe2+-induced oxidative stress on the intracellular Ca2+
      concentration ([Ca2+]i) and on the voltage-sensitive Ca2+ channels (VSCC) of
      chick retinal cells was evaluated in this study. We also analyzed the effect of
      oxidation on the intracellular Na+ concentration ([Na+]i) and on the Ca2+
      dependent release of [3H])gamma-aminobutric acid (GABA) evoked by 50 mM KCI. The
      resting [Ca2+]i was not affected by oxidation, but the [Ca2+]i response
      (delta[Ca2+]i) to K+-depolarization was significantly inhibited under oxidative
      stress conditions. The Ca2+ influx stimulated by membrane depolarization was
      mediated by L- and N-type VSCC, and by N-metyl-D-aspartate (NMDA) receptor
      channel, activated by endogenous glutamate released by glutamatergic cells. In
      cultured retinal cells L-type channels are the major route of Ca2+ influx during
      depolarization and the most affected by oxidative stress. The N-type VSCC seem
      not to be affected by oxidant conditions; they were found to be involved in
      glutamatergic transmission and only indirectly in the release of [3H]GABA evoked
      by K+-depolarization. Although the Ca2+-dependent release of [3H]GABA evoked by
      50 mM KCl is mediated by Ca2+ entry through L-type Ca2+ channels, it is not
      affected by pre-incubation with the oxidant pair. The oxidative stress conditions
      increased the [Na+]i in Ca2+-free medium, by a process dependent of Na+ entry
      through L-type VSCC. The increased permeability of L-type VSCC to Na+ may
      increase the Ca2+-independent release of endogenous glutamate which, by
      activating the NMDA receptors, induces the release of [3H]GABA by reversal of its
      transporter. The equilibrium between the release of GABA and glutamate may play
      an in important role in neuroprotection against excitotoxic insults.

PMID- 9152046
TI  - Theta-activity-dependent and -independent muscarinic facilitation of long-term
      potentiation in guinea pig hippocampal slices.
AB  - Cholinergic input to the hippocampus originates in the septum and diagonal band.
      Guinea pig hippocampal slices in a bath of carbachol, a cholinergic agonist,
      displayed different patterns of rhythmical activities depending on the carbachol
      concentration. Exposure to 50 or 100 microM led to intermittent induction of
      theta-like activities (TLAs). Long-term potentiation (LTP), induced by tetanus.
      was facilitated at concentrations within the optimum range for generating TLAs.
      This facilitation was blocked by the muscarinic receptor antagonist atropine.
      Augmentation of LTP during TLAs was greater than that during the rest period of
      TLAs which, in turn, was greater than that induced without activation of the
      muscarinic receptors. These results suggest that there are two muscarinic
      facilitation processes of LTP, one dependent on and the other independent of
      TLAs, with the former being more easily facilitated than the latter.

PMID- 9152047
TI  - Acute 3-nitropropionic acid intoxication induces striatal astrocytic cell death
      and dysfunction of the blood-brain barrier: involvement of dopamine toxicity.
AB  - Mechanisms underlying the selective vulnerability of the lateral striatal area to
      the toxic effects of 3-nitropropionic acid (3-NPA) were investigated in rats. A
      single exposure to 3-NPA (20 mg/kg, s.c.) induced no deficits in behavior and
      histology, but subsequent injection produced motor symptoms, catalepsy, lip
      smacking, abnormal gait, paddling, rolling, opisthotonos, tremor, recombence,
      somnolence and so on, in 30% of the animals within a few hours. Diffusion
      weighted magnetic resonance imaging of the brains revealed an area of high signal
      intensity in the bilateral striata. By this stage (within a few hours), striatal
      astrocytes had become swollen and disintegrated. Extravasation of immunoglobulin
      G was detected, indicating blood-brain barrier (BBB) dysfunction. Electron
      microscopy revealed edema and disorganization of structures inside the astrocytic
      end-feet around the branches of the lateral striatal artery. Neurons were less
      vulnerable than astrocytes to the 3-NPA injury. Treatment of the rats with D2
      receptor agonist prior to exposure to 3-NPA attenuated the behavioral
      abnormalities and histological damage whereas pretreatment with D2 antagonist
      exacerbated these changes. The concentrations of extracellular dopamine (DA) and
      dihydroxyphenyl acetic acid (DOPAC) were both increased in rats exposed to 3-NPA.
      In vitro imaging of astrocytes revealed a progressive increase in [Ca2+]i after
      superfusion with 3-NPA, and the 'ceiling' level was maintained even after
      extensive washing. DA superfusion also increased the astrocytic [Ca2+]i and this
      increase was reversible. Data indicate that 3-NPA-induced striatal damage was
      associated with astrocytic cell death and dysfunction of the BBB. Intracellular
      edema and extreme Ca2+ overload induced by the toxin were further aggravated by
      an increase in the level of DA activity. These factors acting either singly or in
      combination may trigger astrocyte destruction.

PMID- 9152049
TI  - Inhibition of spinal monosynaptic reflex in newborn rats by aurintricarboxylic
      acid.
AB  - The effect of aurintricarboxylic acid (ATA), an inhibitor of nuclease, on
      glutamatergic synaptic transmission was examined electrophysiologically in the
      isolated spinal cords of newborn rats. Monosynaptic reflex (MSR) was depressed
      about 20%, 50 min after exposure to 100 microM of ATA. Pretreatment with APV, a N
      methyl-D-aspartate (NMDA) type receptor antagonist, depressed MSR by about 10%,
      but additional application of ATA did not affect the MSR further. In contrast,
      the remaining MSR following treatment with DNQX, a non-NMDA type receptor
      antagonist, in the Mg2+-free medium was almost completely inhibited by addition
      of ATA. ATA depressed NMDA- but not D,L-alpha-amino-3-hydroxy-5-methyl-4
      isoxalone propionic acid (AMPA)- or kainate-induced depolarization in the medium
      containing normal ionic composition. Thus it is concluded that the reduction of
      MSR by ATA is due to blockade of NMDA type but non-NMDA type glutamate receptors.
      The present study also confirmed the previous conclusion that Ia monosynaptic
      transmission in the spinal cord of the newborn rat is mediated by NMDA as well as
      non-NMDA type glutamate receptors.

PMID- 9152048
TI  - Two components of transmitter release in retinal bipolar cells: exocytosis and
      mobilization of synaptic vesicles.
AB  - Ca2+-transmitter release coupling was examined using bipolar cells with large
      presynaptic terminals dissociated from the goldfish retina. Presynaptic Ca2+
      current (I(Ca)) was recorded under the whole-cell voltage clamp. Release of
      excitatory amino acid transmitter was simultaneously monitored as the current
      through N-methyl-D-asperate (NMDA) receptors of reporter cells or as the membrane
      capacitance (C(m)) change associated with exocytosis. When I(Ca) was activated by
      a long depolarizing pulse, a double-peaked transmitter-induced current (I(tr))
      was elicited in reporter cells. The rapid component of I(tr) was evoked
      immediately after the onset of depolarization, and was affected only slightly by
      intracellularly applied Ca2+ chelators. The delayed slow component of I(tr) was
      elicited during depolarization once a fixed amount of Ca2+ was accumulated in
      presynaptic terminals, and its appearance was suppressed or retarded by Ca2+
      chelators. Two components of transmitter release were also recognized by
      monitoring C(m) changes elicited by the activation of I(Ca). These results
      suggest that bipolar cells have at least two pools of synaptic vesicles; a small,
      immediately releasable pool and a large releasable pool. The rapid and the
      delayed slow components of transmitter release may reflect exocytosis and
      mobilization of synaptic vesicles, respectively.

PMID- 9152051
TI  - Scandinavian Society for the Study of Diabetes 32nd annual meeting. Gothenburg,
      Sweden, 23-25 May 1997. Abstracts.

PMID- 9152050
TI  - Light microscopic comparison of the patterns of glutamate-like and homocysteate
      like immunoreactivities in rat dorsal lateral geniculate after combined visual
      cortical and retinal ablations.
AB  - To study the contribution of retinal and cortical afferents to the patterns of
      glutamate- and homocysteate-like immunoreactivities in dorsal lateral geniculate,
      combined retinal and cortical ablations were performed in rats. In controls,
      glutamate immunoreactivity was in terminal-like dots and neurons. Homocysteate
      immunoreactivity was in small puncta. In lesioned animals, most glutamate
      immunoreactive dots disappeared. In contrast, abundant puncta resembling parts of
      glial cells were immunoreactive for homocysteate.

PMID- 9152052
TI  - International Association for Dental Research. Divisional abstracts.

PMID- 9152053
TI  - Finance. Measuring up.

PMID- 9152054
TI  - Internet. Navigating MEDLINE.

PMID- 9152055
TI  - Pharmaceuticals ... medicine labels are hard to read.

PMID- 9152056
TI  - Home care goes corporate.
AB  - Some 18,000 home health agencies dot today's landscape--one of health care's last
      cottage industries. But the spread of managed care, plus long-promised Medicare
      payment reform, will change all that. Waves of consolidation and cost-cutting
      won't be far behind.

PMID- 9152057
TI  - With costs and demands for expertise rising, health care is increasingly putting
      computer systems on ... remote control.
AB  - Outside managers already have a grip on running the information systems that
      power and support health care. It's their largest market--and it's just getting
      started. Investment analysts see a boom in the making, fueled by accelerating
      costs and demands for expertise.

PMID- 9152058
TI  - Humana gets happy. But can its new look and customer-friendly attitude reverse an
      earnings slump?
AB  - After a series of strategic missteps and a stall in earnings, the HMO aims to
      buff up its image with a new emphasis on pleasing doctors and patients. Now if
      only investors agree to wait out the makeover.

PMID- 9152059
TI  - Consumers. What a little arm-twisting can do.

PMID- 9152060
TI  - Compensation. Show them the money.

PMID- 9152061
TI  - Software. Data rich, information poor.

PMID- 9152062
TI  - Pediatric care. Waking up to the crib's dangers.

PMID- 9152063
TI  - Treatment of uveitis by oral administration of retinal antigens: results of a
      phase I/II randomized masked trial.
AB  - PURPOSE: To evaluate the effect and safety of the oral administration of retinal
      antigens as a treatment of ocular inflammation. METHODS: In a phase I/II
      randomized masked trial, patients with endogenous uveitis who were dependent on
      immunosuppressive agents were randomly assigned to receive either retinal S
      antigen alone (10 patients), retinal S antigen and a mixture of soluble retinal
      antigens (10 patients), a mixture of soluble retinal antigens alone (10
      patients), or placebo (15 patients). An attempt was then made to taper patients
      completely off their standard immunosuppressive therapy over an 8 week period.
      The primary study endpoint was time to ocular inflammatory attack. The secondary
      study endpoint was the ability to taper patients completely off their
      immunosuppressive or cytotoxic medication within 8 weeks. RESULTS: Time to
      development of the main study endpoint was not statistically significantly
      different for any of the four treatment groups. However, the group receiving the
      purified S antigen alone appeared to be tapered off their immunosuppressive
      medication more successfully compared with patients given placebo (P = .08),
      whereas all the other groups appeared to do worse than did those receiving
      placebo. No toxic effects attributable to any treatment were observed.
      CONCLUSIONS: This phase I/II study is the first to test the use of orally
      administered S antigen in the treatment of uveitis. Although not statistically
      significant, patients given S antigen were more likely to be tapered off their
      chronically administered systemic immunosuppressive therapy than were the other
      groups tested.

PMID- 9152064
TI  - Blood serum interleukin-1 receptor antagonist in pars planitis and ocular Behcet
      disease.
AB  - PURPOSE: To determine the levels of interleukin-1 receptor antagonist (IL-1ra) in
      the blood serum of patients with idiopathic bilateral pars planitis and Behcet
      disease. METHODS: Five milliliters of blood was with-drawn from the cubital vein
      of 91 patients (58 with the ocular type and five with the combined type of Behcet
      disease; 28 with pars planitis) and 36 volunteers. Serum was separated from these
      samples and stored at -70 C until assayed. Interleukin-1 receptor antagonist
      levels were determined by human IL-1ra enzyme-linked immunosorbent assay kits. In
      patients not receiving any systemic medication, one serum sample was obtained
      before initiating treatment and another when the patients had been under full
      medical treatment for 6 weeks or more. RESULTS: Pretreatment mean +/- SD serum IL
      1ra levels were 320 +/- 32 pg/ml for the patients with pars planitis, 380 +/- 54
      pg/ml for patients with Behcet disease, and 271 +/- 29 pg/ml for the control
      subjects (no statistical significance). During treatment, a mean serum level of
      352 +/- 37 pg/ml was observed in patients with pars planitis (not significantly
      different from control subjects) and 538 +/- 79 pg/ml in patients with ocular
      Behcet disease (P = .0116 compared with control subjects). The greatest increase
      in IL-1ra levels was observed in patients with Behcet disease who received a
      combination of cyclosporine and corticosteroids. CONCLUSIONS: Because IL-1ra is
      one of the natural immunomodulating molecules, the significant increase of serum
      IL-1ra levels, especially after combined treatment with cyclosporine and
      corticosteroids, could indicate that the therapeutic effects of this regimen may
      be mediated through its effects on this molecule.

PMID- 9152065
TI  - Monocyte chemotactic protein-1 in proliferative vitreoretinal disorders.
AB  - PURPOSE: To investigate whether the chemokines monocyte chemotactic protein-1
      (MCP-1) and interleukin-8 (IL-8) are involved in the pathogenesis of
      proliferative vitreoretinal disorders and to study their possible interaction
      with IL-6. METHODS: In a prospective study of 125 consecutive patients (125
      eyes), vitreous and paired serum samples were obtained and were assayed for MCP-1
      and IL-8. Levels of IL-6 were determined by proliferation of the IL-6-dependent
      hybridoma cell line 7TD1. RESULTS: Monocyte chemotactic protein-1 was detected in
      13 (48%) of 27 vitreous samples from patients with retinal detachment, in five
      (63%) of eight samples from patients with macular pucker, in 31 (72%) of 43
      samples from patients with proliferative vitreoretinopathy, and in 32 (76%) of 42
      samples from patients with proliferative diabetic retinopathy, but not in samples
      from five patients with idiopathic epiretinal membrane. There was a significant
      (P = .049) correlation between the incidence of MCP-1 detection in retinal
      detachment, macular pucker, and proliferative vitreoretinopathy groups and the
      severity of proliferation. Interleukin-8 was detected in two vitreous samples
      from eyes with retinal detachment, in two samples from eyes with proliferative
      vitreoretinopathy, and in three samples from eyes with proliferative diabetic
      retinopathy. Monocyte chemotactic protein-1 levels in the vitreous samples were
      positively correlated with IL-6 levels (r = .31, P = .01). Interleukin-6 levels
      were significantly (P = .0097) greater in vitreous samples with than without
      detectable levels of MCP-1. CONCLUSION: Monocyte chemotactic protein-1 is present
      in a substantial percent of vitreous samples from eyes with proliferative
      vitreoretinal disorders and may help in stimulating the infiltration of monocytes
      and macrophages into eyes with these disorders.

PMID- 9152066
TI  - Autoimmune retinopathy in the absence of cancer.
AB  - PURPOSE: To report the clinical and immunologic features of two patients with
      progressive retinal degeneration and circulating antiretinal antibodies without
      systemic malignancy. METHODS: Two patients were followed up for 5 to 7 years.
      Comprehensive medical and ophthalmic examinations and visual function testing
      included manual perimetry and standardized electroretinography. Patient sera were
      tested for antiretinal antibodies by Western blot and immunoperoxidase indirect
      cytochemistry techniques. RESULTS: Two patients had family history of autoimmune
      disease. Each had severe monocular visual loss with photopsia, a ring scotoma,
      and abnormal electroretinogram despite a normal-appearing ocular fundus. One had
      a flat electroretinogram; the other had inner retina dysfunction, with selective
      b wave loss and abnormal oscillatory potentials. Both patients' sera had
      antiretinal antibodies that specifically labeled the inner plexiform layer of
      donor retina by indirect immunoperoxidase testing. Neither had any sign of
      cancer. CONCLUSIONS: In two patients without systemic malignancy, the symptoms,
      perimetric findings, and normal fundus appearance resembled cancer associated
      retinopathy. Electroretinography and antibody findings indicating dysfunction of
      the inner retina are distinct from those of cancer-associated retinopathy. These
      two cases raise the possibility of an autoimmune mechanism for retinal
      degeneration that is not cancer associated. Further study is necessary to
      determine the role of antiretinal antibodies in these patients.

PMID- 9152067
TI  - Retinal function abnormalities in membranoproliferative glomerulonephritis type
      II.
AB  - PURPOSE: To characterize retinal electrophysiologic and psychophysical
      abnormalities associated with membranoproliferative glomerulonephritis type II.
      METHODS: Three adults with membranoproliferative glomerulonephritis type II were
      studied. Retinal function was measured psychophysically (automated perimetry,
      Farnsworth D-15 color vision testing, and dark adaptometry) and
      electrophysiologically (full-field flash electroretinography and electro
      oculography). RESULTS: Two symptomatic individuals had prominent drusenlike
      deposits and retinal pigment epithelial disturbances, findings characteristic of
      membranoproliferative glomerulonephritis type II retinopathy. These individuals
      had mild visual field and color vision abnormalities, prolonged dark adaptation,
      and delayed electroretinographic dark-adapted dim and bright flash responses of
      normal amplitude. The electro-oculogram of the most severely affected individual
      was abnormal. The third individual who was asymptomatic had the mildest fundus
      abnormalities and exhibited normal psychophysical and electrophysiologic
      responses. CONCLUSIONS: Membranoproliferative glomerulonephritis type II
      retinopathy may be associated with symptomatic and measurable psychophysical and
      electrophysiologic abnormalities of retinal function.

PMID- 9152068
TI  - Surgical management of posteriorly dislocated silicone plate haptic intraocular
      lenses.
AB  - PURPOSE: To report a large series of delayed posterior dislocation of silicone
      plate haptic intraocular lenses after Nd:YAG laser capsulotomy and discuss the
      surgical management of this complication. METHODS: We reviewed the records of 11
      consecutive patients (11 eyes) with delayed onset of posterior dislocation of a
      plate haptic silicone intraocular lens. The cause of the posterior capsular
      defect, time to dislocation, surgical management techniques, complications, and
      visual outcome were recorded. RESULTS: In eight of the 11 eyes, the silicone
      plate haptic intraocular lens dislocated an average of 1.8 months (range, 0 to
      6.5 months) after Nd:YAG posterior capsulotomy. The other three eyes had surgical
      complications at the time of cataract extraction that compromised posterior
      capsular or zonular integrity and led to silicone plate haptic intraocular lens
      dislocation from 9 weeks to 6 months (mean, 3.6 months) postoperatively. Surgical
      management consisted of pars plana vitrectomy with intraocular lens repositioning
      (six eyes) or exchange (five eyes). The average follow-up period after
      intraocular lens repositioning or exchange was 6.5 months (range, 1 to 14
      months). Best-corrected visual acuity at the last follow-up examination measured
      20/40 or better in all but one eye that had preexisting macular disease.
      CONCLUSIONS: Cataract surgeons and patients should be aware of the potential for
      plate haptic silicone intraocular lenses to undergo delayed posterior dislocation
      through capsular defects. This complication can be managed effectively with
      vitrectomy and either repositioning or exchange of the implant. Postoperative
      visual acuity is generally excellent, and complications are minimal.

PMID- 9152069
TI  - Comparison of astigmatism after penetrating keratoplasty by experienced cornea
      surgeons and cornea fellows.
AB  - PURPOSE: We compared surgically induced astigmatism after penetrating
      keratoplasty performed by supervised cornea fellows and experienced cornea
      surgeons. METHODS: Data were collected by retrospective chart review of 166 cases
      (166 eyes) of penetrating keratoplasty: 63 performed by two cornea surgeons and
      103 by four cornea fellows. Astigmatism was calculated using scalar and vector
      methods. Vector analysis was performed on 109 of 166 eyes. Two techniques were
      compared: intraoperative keratometry and suture adjustment and the torque
      antitorque running suture technique with no intraoperative keratometry or suture
      adjustment. RESULTS: Mean surgically induced scalar astigmatism changed from
      preoperative astigmatism by 3.27 diopters (fellows) and 2.94 diopters (attending
      surgeons). In 109 cases, surgically induced vector cylinder changed from
      peroperative astigmatism by 4.21 diopters at 98 degrees (fellows) and 4.25
      diopters at 114 degrees (surgeons). Surgically induced vector astigmatism changed
      from preoperative astigmatism by 4.67 diopters at 93 degrees in the first 6
      months (fellows) and by 3.79 diopters at 103 degrees in the second 6 months.
      Analysis of x-axis and y-axis components of the surgically induced vector
      cylinder showed that the majority of the astigmatism was induced in the y-axis
      and that this difference was significant (P < .001) in all comparisons,
      independent of technique or surgeon group. CONCLUSIONS: Penetrating keratoplasty
      performed by supervised cornea fellows resulted in similar rates of surgically
      induced vector astigmatism, surface asymmetry, and surface regularity as that by
      experienced surgeons. Fellows induced significantly more with-the-rule
      astigmatism, but this tendency decreased with further training. Penetrating
      keratoplasty astigmatic outcomes were not significantly different whether or not
      intraopertive keratometry and suture adjustment were utilized. This study
      supports the concept that increased experience with corneal transplantation
      improves the outcome of penetrating keratoplasty by using the criterion of
      postoperative astigmatism as a measures.

PMID- 9152070
TI  - A comparison of retinal and choroidal hemodynamics in patients with primary open
      angle glaucoma and normal-pressure glaucoma.
AB  - PURPOSE: To quantify, compare, and assess differences between retinal and
      choroidal hemodynamics in normal control subjects and patients with ocular
      hypertension, primary open-angle glaucoma, and normal-pressure glaucoma. METHODS:
      Video fluorescein angiograms were made in 20 normal subjects, 11 patients with
      ocular hypertension, 45 patients with primary open-angle glaucoma, and 43
      patients with normal-pressure glaucoma. Choroidal dye build-up curves were
      analyzed using an exponential model. The model time constant tau reflected the
      local blood refreshment time, the time needed to replace the blood volume in a
      tissue volume. Retinal arteriovenous passage time was estimated from the time
      lapse between retinal arterial and venous dye curves. RESULTS: The retinal
      arteriovenous passage time was longer in patients with primary open-angle
      glaucoma compared with normal subjects and patients with normal-pressure
      glaucoma; the average arteriovenous passage times (+/-SEM) in normal subjects and
      in patients with ocular hypertension, primary open-angle glaucoma, and normal
      pressure glaucoma were, respectively, 2.44 +/- 0.19, 2.90 +/- 0.37, 3.02 +/-
      0.17, and 2.55 +/- 0.15 seconds. Choroidal tau was longest in the normal-pressure
      glaucoma group but not as long in the primary open-angle glaucoma group; tau
      values in normal subjects and patients with ocular hypertension, primary open
      angle glaucoma, and normal-pressure glaucoma were, respectively, 4.6 +/- 0.29,
      5.6 +/- 0.69, 6.2 +/- 0.39, and 7.1 +/- 0.33 seconds. CONCLUSIONS: Whereas
      choroidal circulation is especially slower in patients with normal-pressure
      glaucoma, retinal circulation is delayed in patients with primary open-angle
      glaucoma. The choroidal and retinal vascular systems behave differently in
      primary open-angle and normal-pressure glaucoma, which may be important in the
      management of glaucoma.

PMID- 9152071
TI  - Indocyanine green angiography of the peripapillary region in glaucomatous eyes by
      confocal scanning laser ophthalmoscopy.
AB  - PURPOSE: To investigate the peripapillary region in glaucomatous eyes by
      indocyanine green angiography. METHODS: Indocyanine green angiography of the
      optic disk and peripapillary region was evaluated by modified confocal scanning
      laser ophthalmoscopy in 22 eyes of 22 patients with glaucoma and in 10 normal
      eyes of 10 control patients with unilateral choroidal melanoma. The occurrence
      and extent of indocyanine green angiographic anomalies were correlated with optic
      disk morphology and the severity of glaucoma. RESULTS: In the 32 eyes of 32
      patients, two types of peripapillary defects were identified in the late-phase
      angiograms. The first was hypofluorescent areas in the peripapillary region and
      was more common in eyes with glaucoma (P < .02); their occurrence and extent
      correlated with age (P < .01). In nine of the 17 eyes, alpha (peripheral) zone
      peripapillary atrophy corresponded with the areas of peripapillary indocyanine
      green hypofluorescene. The second defect, hypofluorescent halos adjacent to and
      extending around the full circumference of the optic disk margins, did not
      correlate with any of the study factors. CONCLUSIONS: Indocyanine green
      angiography showed areas of hypofluorescene in the peripapillary region in late
      phase angiograms in 68% of glaucomatous eyes compared with 20% of control eyes.
      These hypofluorescent areas might be either of result of blockage of background
      fluorescence by pigment or caused by an absence of vascular tissue
      (choriocapillaris).

PMID- 9152072
TI  - Mapping structural damage of the optic disk to visual field defect in glaucoma.
AB  - PURPOSE: To evaluate the relation between the location of focal visual field
      defects and optic disk damage in eyes with glaucoma by short-wavelength automated
      perimetery and confocal scanning laser ophthalmoscopy. METHODS: In 14 patients
      (14 eyes) with open-angle glaucoma, focal optic disk damage, and focal visual
      field loss, we obtain visual fields with short-wave-length automated perimetry.
      The short-wavelength automated perimetry visual field was divided into 21 zones,
      representing retinal nerve fiber layer arcuate bundles. Test points were compared
      with a normative database. The optic disk was assessed with a confocal scanning
      laser ophthalmoscope. Optic disk measurements were calculated in 10-degree
      sectors and compared with a normative database using a new measure, the rim area
      ratio, which adjusts for individual differences in disk size. RESULTS: The mean
      number (+/-SD) of damaged visual field zones was 3.9 (+/-1.9), and the mean
      number of damaged rim sectors was 5.0 (+/-2.9). Focal defects on the optic disk
      and on short-wavelength automated perimetry were topographically related with
      specific damaged visual field zones corresponding to specific damaged rim
      sectors. CONCLUSIONS: In patients with open-angle glaucoma with focal optic disk
      damage and focal visual field loss, defects in optic disk and short-wavelength
      automated perimetry are topographically related. The rim area ratio can be used
      to identify focal optic nerve defects.

PMID- 9152073
TI  - Optic nerve contact and compression by the carotid artery in asymptomatic
      patients.
AB  - PURPOSE: To estimate the frequency and clinical correlates of contact and
      compression of the intracranial optic nerve by the supraclinoid carotid artery in
      asymptomatic patients. METHODS: In a retrospective study, we identified
      asymptomatic patients who had undergone magnetic resonance imaging with sequences
      that could be used to evaluate the relation between the intracranial optic nerve
      and the carotid artery. These patients underwent neuroimaging evaluations for
      reasons unrelated to loss of vision, optic neuropathy, or carotid artery
      disorders. The relation between the optic nerve and carotid artery was graded in
      a standardized manner. The effect of a number of clinical covariates on the risk
      of compression was evaluated using multiple logistic regression. RESULTS: The
      frequencies of some of the artery-nerve relationships included contact of one or
      both optic nerves in 70 (70%) of 100 patients; bilateral compression in 12 (12%)
      of 100 patients; and unilateral compression with no arterial contact or
      compression on the opposite side in five (5%) of 100 patients. The estimated odds
      of compression were significantly increased as the diameter of the carotid artery
      increased. CONCLUSIONS: Among asymptomatic patients, supraclinoid carotid artery
      contact with the intracranial optic nerve occurs frequently. Anatomic
      compression, on the other hand, especially when unilateral, occurs infrequently.
      The risk of anatomic compression of the optic nerve is directly proportional to
      the diameter of the carotid artery.

PMID- 9152074
TI  - Tolerance and uveitis.

PMID- 9152075
TI  - Harvesting a lamellar graft from a corneoscleral button: a new technique.
AB  - PURPOSE: To describe a new technique for harvesting a lamellar graft from a
      corneoscleral button in the absence of an artificial anterior chamber. METHODS:
      Two layers of sterile fine-weave fabric were wrapped tightly around a glass
      orbital implant. The corneoscleral button was sutured firmly at its scleral rim
      onto the fabric. The lamellar graft then was dissected in the regular fashion.
      RESULTS: The lamellar graft was successfully obtained. During the dissection, the
      donor cornea and its supporting fabric-covered glass ball were easily handled,
      and there was minimal risk of perforation of the posterior lamella of the donor
      cornea. CONCLUSION: This simple technique allows a lamellar graft to be easily
      obtained from a corneoscleral button without specialized and expensive equipment.

PMID- 9152076
TI  - Ophthalmic dirofilariasis.
AB  - PURPOSE: To report a rare case of ophthalmic dirofilariasis in a 68-year-old man
      with sudden, intense pain and itching in the left eye. The nematode was located
      in the eye and recognized as Dirofilaria repens. METHODS: Slit-lamp examination
      disclosed a moving nematelminth under the bulbar conjunctiva of the left eye. The
      nematode was surgically removed. RESULTS: The nematelminth surgically removed
      from the subconjunctival space was identified as D repens on the basis of
      transverse sections and its macroscopic characteristics. CONCLUSION: It is
      important to identify the nematode as D repens, based on both its microscopic and
      macroscopic characteristics, to avoid treatment with anthelminthic agents. The
      surgical removal of the worm is the sole recommended treatment.

PMID- 9152077
TI  - Adie syndrome as the initial sign of primary Sjogren syndrome.
AB  - PURPOSE: To report Adie syndrome as the initial sign of primary Sjogren syndrome.
      METHODS: Case report. RESULTS: Adie syndrome was associated with necrotizing
      gingivitis and xerostomia. Antibodies against Ro (SS-A) were present. Prednisone
      and antimalarial drugs were ineffective in treating Adie syndrome but improved
      the necrotizing gingivitis. CONCLUSION: Search for Sjogren syndrome is mandated
      in patients with Adie syndrome. The latter condition is likely related to
      ganglionitis, a mechanism responsible for peripheral nervous system involvement
      in primary Sjogren syndrome.

PMID- 9152078
TI  - Juvenile pilocytic astrocytoma masquerading as amblyopia.
AB  - PURPOSE: A healthy 13-year-old girl, previously diagnosed with amblyopia in her
      right eye, was seen in consultation after her vision continued to decrease.
      METHODS: A complete ophthalmologic examination including visual field testing and
      optic nerve photography was performed in the neuro-ophthalmologic clinic.
      Magnetic resonance imaging study was also obtained. RESULTS: Visual sensory
      deficits and pale optic nerves were noted on clinical examination. Visual field
      testing showed a chiasmatic junctional defect. Magnetic resonance imaging
      verified a large chiasmatic mass, histologically proven to be a juvenile
      pilocytic astrocytoma. CONCLUSION: Early recognition of signs and symptoms of
      chiasmatic lesions is essential for preventing visual loss.

PMID- 9152080
TI  - Retinal venous beading with recurrent preretinal hemorrhage.
AB  - PURPOSE: To report a patient with idiopathic retinal venous beading and recurrent
      preretinal hemorrhage. METHOD: Case report of a 17-year-old girl with bilateral
      retinal venous beading, greater in the left eye than in the right eye, and
      recurrent preretinal hemorrhage in the left eye. RESULTS: Complete blood cell
      count, platelet count, blood glucose level, and hemoglobin electrophoresis were
      normal. Fluorescein angiography showed normal retinal arterial and venous filling
      with no evidence of retinal capillary nonperfusion or neovascularization.
      CONCLUSION: Idiopathic retinal venous beading may be associated with recurrent
      preretinal hemorrhage, even in the absence of retinal ischemia or
      neovascularization.

PMID- 9152079
TI  - Phototoxic reactions caused by sodium fluorescein.
AB  - PURPOSE: To report three cases of phototoxic reactions to intravenous fluorescein
      for retinal angiography and to describe provocative testing in a volunteer.
      METHODS: Three patients with phototoxic reactions were interviewed, and one
      volunteer underwent a controlled challenge test by applying a potent sunscreen
      and exposing skin areas to direct sunlight before and after fluorescein
      administration. RESULTS: All patients experienced marked cutaneous erythema,
      edema, and pain to sun-exposed areas within 1 hour of exposure. The reaction
      faded during a variable period of time, and one case resulted in mild epidermal
      desquamation and prolonged discomfort. We noted minimal skin changes in the
      volunteer who was exposed to the sun before fluorescein administration; however,
      marked blanching erythema and pain were noted after fluorescein administration
      and sunlight. CONCLUSIONS: Consistent with its in vitro properties as a
      photodynamic dye, fluorescein may rarely act as a phototoxic agent in humans at
      doses employed for fluorescein angiography.

PMID- 9152081
TI  - Epiretinal membrane and traction retinal detachment complicating laser-induced
      chorioretinal venous anastomosis.
AB  - PURPOSE: To report a patient with a sight-threatening complication of laser
      induced chorioretinal venous anastomosis for treatment of central retinal vein
      occlusion. METHOD: A 69-year-old woman with a nonischemic central retinal vein
      occlusion underwent focal argon laser photocoagulation treatment to create a
      chorioretinal venous anastomosis. RESULTS: Massive preretinal fibrosis and
      traction retinal detachment developed over the area of argon laser
      photocoagulation, which required vitreous surgery. CONCLUSION: Laser-induced
      chorioretinal venous anastomosis to treat central retinal vein occlusion can be
      associated with severe complications, underscoring the need for additional study
      of this new treatment modality.

PMID- 9152083
TI  - Use of the ganciclovir implant for treating cytomegalovirus retinitis secondary
      to immunosuppression after bone marrow transplantation.
AB  - PURPOSE: To report a case in which we treated cytomegalovirus retinitis using an
      intravitreal ganciclovir sustained-release device in a patient negative for the
      human immunodeficiency virus, with a history of myeloproliferative syndrome with
      myelofibrosis and profound immunosuppression after allogeneic bone marrow
      transplantation. METHODS: Case report. Review of medical records and fundus
      photographs. RESULTS: After the ganciclovir device was implanted, the
      cytomegalovirus retinitis did not progress, and visual acuity improved. We
      removed the device 9 months after implantation. CONCLUSIONS: The ganciclovir
      sustained-release device may be useful for treating cytomegalovirus retinitis in
      patients without the acquired immunodeficiency syndrome who are profoundly
      immunosuppressed and fail conventional intravenous therapy. If immune suppression
      is of limited duration, the device can be removed.

PMID- 9152082
TI  - Retinal perivasculitis in an immunocompetent patient with systemic herpes simplex
      infection.
AB  - PURPOSE: To describe a case of retinal perivasculitis in an immunocompetent
      patient with systemic herpes simplex infection. METHODS: Polymerase chain
      reaction amplifications were performed for aqueous and blood samples using
      primers specific for the following members of the herpesvirus family:
      cytomegalovirus, Epstein-Barr virus, herpes simplex virus (types 1 and 2), and
      varicella-zoster virus. The patient was placed on intravenous acyclovir and
      systemic corticosteroids. RESULTS: A positive polymerase chain reaction signal
      was found only for herpes simplex virus type 1. Vision in the left eye improved
      from light perception to 20/25, and signs of retinal perivasculitis resolved.
      CONCLUSION: The use of molecular diagnostic modalities in clinical practice may
      aid in determining infectious etiologies in patients with atypical clinical
      manifestations.

PMID- 9152084
TI  - Sarcoidosis manifesting as uveitis and menometrorrhagia.
AB  - PURPOSE: To report a rare systemic manifestation of sarcoidosis identified in a
      47-year-old white woman while she was undergoing evaluation for bilateral
      recurrent uveitis. METHODS: The patient underwent clinical and laboratory
      evaluation for bilateral recurrent uveitis including serologic and radiologic
      testing, a gallium scan, and an endometrial biopsy. RESULTS: Although the
      serologic tests and chest x-ray were normal, the gallium scan was consistent with
      sarcoidosis, and the endometrial biopsy provided a tissue diagnosis. CONCLUSION:
      Sarcoidosis involving the female reproductive tract is rare. A thorough review of
      systems is crucial in the evaluation of any patient with recurrent uveitis.

PMID- 9152085
TI  - Combined macular hole and cataract surgery.
AB  - PURPOSE: Cataract often develops after macular hole surgery, necessitating
      cataract surgery. We report a combination of macular hole surgery and cataract
      surgery on four eyes of four patients. METHODS: Four eyes of four patients had a
      full-thickness stage III or IV macular hole and some degree of cataract. Combined
      cataract surgery with intraocular lens implant and macular hole surgery was
      associated with intravitreal perfluoropropane at 15% concentration and with face
      down positioning for 21 days. RESULTS: After combined cataract and macular hole
      surgery, the rim of subretinal fluid resolved successfully in four eyes of four
      patients. Twelve months after surgery, the macular hole reopened in one eye in
      association with the new onset of macular pucker. Best-corrected visual acuities
      ranged from 20/25 to 20/100 12 months after surgery, while preoperative visual
      acuities with best correction were 20/70 to 20/200. CONCLUSIONS: In selected
      cases, a combination of cataract surgery with intraocular lens implant and
      macular hole surgery offers advantages. This combined approach warrants
      consideration.

PMID- 9152086
TI  - Visual field loss caused by retinal vascular occlusion after vitrectomy surgery.
AB  - PURPOSE: To report complete superonasal retinal arterial occlusion with resulting
      temporal visual field loss after uneventful pars plana vitrectomy with gas-fluid
      exchange. METHOD: Case report. RESULTS: Superonasal retinal arterial occlusion
      was observed 12 days after vitrectomy surgery. Within 10 weeks, the artery
      reperfused, leaving minimal vascular attenuation and mild optic atrophy.
      CONCLUSIONS: Uneventful vitrectomy surgery can be associated with notable
      peripheral visual field loss caused by arterial occlusion in the immediate
      postoperative period. Rapid resorption of the intraocular gas and timely
      postoperative examination may disclose retinal arteriolar occlusion; otherwise,
      subsequent reperfusion may leave little evidence of the vascular event.

PMID- 9152087
TI  - Sulfur hexafluoride and perfluoropropane do not escape from a plastic syringe
      closed with a stopcock.
AB  - PURPOSE: To evaluate during various intervals of time the escape of long-acting
      gases contained in a plastic syringe closed with a stopcock or a plastic cap.
      METHODS: A 60-ml plastic syringe was filled or partially filled with a long
      acting gas, either sulfur hexafluoride or perfluoropropane. The tip of the
      syringe was closed with either a stopcock or the syringe's plastic cap. After
      various intervals of time, the concentration of the long-acting gas in the
      syringe was measured by gas chromatography. RESULTS: The concentration of both
      long-acting gases was higher than 98% at 24 hours after filling when the syringe
      was closed with a stopcock; however, it was less than 41% when the syringe was
      filled and capped tightly with its plastic cap. CONCLUSION: The proportion of
      long-acting gases escaping in 24 hours from a filled syringe capped with a
      stopcock is clinically insignificant.

PMID- 9152088
TI  - Ultrasound biomicroscopy in the diagnosis of persistent hypotony after
      vitrectomy.
AB  - PURPOSE: To describe a case of persistent hypotony after an otherwise successful
      vitreous surgery for epiretinal membrane, in which ciliochoroidal detachment was
      detected by ultrasound biomicroscopy but not by ophthalmoscopy. METHOD: We used
      ultrasound biomicroscopy to determine the cause of persistent postoperative
      hypotony. RESULTS: Ultrasound biomicroscopy clearly disclosed ciliochoroidal
      detachment. In an attempt to resolve ciliochoroidal detachment, we performed
      vitrectomy and fluid-gas exchange combined with diathermy around the sites of
      sclerotomy. Postoperatively, the regression of ciliochoroidal detachment was
      confirmed by ultrasound biomicroscopy. CONCLUSIONS: Using ultrasound
      biomicroscopy, we were able to visualize ciliochoroidal detachment and its
      regression clearly, which we had not observed during ophthalmoscopy.

PMID- 9152089
TI  - Nocardia scleritis.
AB  - PURPOSE: To describe a case of Nocardia scleritis, an unusual ocular infection.
      METHODS: Case report and review of pertinent literature. RESULTS: An 83-year-old
      man with leukocytoclastic vasculitis was initially examined for infectious
      necrotizing scleritis after explantation of an extruded scleral buckle. The
      patient was successfully treated with sulfonamides. CONCLUSIONS: Nocardia
      asteroides may cause infectious scleritis in the absence of cataract surgery or
      trauma. Treatment with sulfonamides can result in a satisfactory outcome.

PMID- 9152090
TI  - Optic nerve hypoplasia: absence of posterior pituitary bright signal on magnetic
      resonance imaging correlates with diabetes insipidus.

PMID- 9152091
TI  - Comparison of suture-in and suture-out postkeratoplasty astigmatism with single
      running suture or combined running and interrupted sutures.

PMID- 9152092
TI  - The rationale and ethics of medication-free research in schizophrenia.
AB  - Schizophrenia research is receiving intense scrutiny from an ethical perspective.
      Medication-free protocols present a most vexing dilemma in that they greatly
      enhance the opportunity for advancing knowledge but also raise the prospect of
      withholding known effective treatment. In this article, we discuss the purpose of
      medication-free protocols in new drug development and nontreatment research.
      Potential benefits and risks associated with drug discontinuation are evaluated,
      and methods for minimizing risk and increasing benefits are proposed as
      guidelines for the protection of individual subjects. The complex problem of
      informed consent also is addressed. Medication-free research in schizophrenia is
      difficult, but it can be conducted relatively, safely with freely consenting,
      competent subjects. Assurance that studies meet this standard is required. We
      believe that such investigations can meet high standards of ethics and subject
      protection, and that a radical revision of procedures for research review and
      implementation is not indicated.

PMID- 9152093
TI  - Medication-free research with schizophrenic patients. A European perspective.

PMID- 9152094
TI  - The call of the sirens. Navigating the ethics of medication-free research in
      schizophrenia.

PMID- 9152095
TI  - A quantitative analysis of smooth pursuit eye tracking in monozygotic twins
      discordant for schizophrenia.
AB  - BACKGROUND: Previous studies of discordant monozygotic (MZ) twins have suggested
      that abnormal smooth pursuit eye tracking is an indicator of genetic liability
      for schizophrenia. We attempted to replicate this in a different sample of twins.
      METHODS: Probands from 12 sets of MZ twins discordant for schizophrenia who met
      DSM-III-R criteria for schizophrenia or schizoaffective disorder and their co
      twins without psychiatric diagnosis (except 2 with a history of substance abuse)
      and 12 sets of normal control MZ twins. Psychiatric diagnosis was based on
      Structured Clinical Interview; monozygosity was based on analysis of 19 red blood
      cell antigens. Smooth pursuit eye movement gain (equal to the ratio of eye-target
      velocity) and numbers, amplitudes, and subtypes of saccadic eye movements were
      compared. Measures were derived from computer analysis of digitized infrared
      oculographic recordings of constant velocity (16.67 degrees per second) smooth
      pursuit eye tracking. RESULTS: Quantitative measures of eye tracking for the
      affected twin were inferior to those of the unaffected co-twin, with affected
      twins showing significant decreases in gain and significant increases in numbers
      and amplitudes of total and intrusive saccades. Moreover, whereas means for the
      group of affected twins differed significantly from those of normal controls on
      measures of gain and total saccades, means for the group of unaffected co-twins
      were well within the normal range. CONCLUSIONS: These data are consistent with
      the hypothesis that abnormal eye tracking is associated with the expression of
      illness, or phenotype, in schizophrenia, at least in this twin sample. The data
      raise questions regarding the use of eye tracking measurement for identifying
      putative gene carriers among at-risk relatives in genetic linkage studies of
      schizophrenia.

PMID- 9152096
TI  - Smooth pursuit eye tracking in twins. A critical commentary.

PMID- 9152097
TI  - Magnetic source imaging evidence of sex differences in cerebral lateralization in
      schizophrenia.
AB  - BACKGROUND: It has been postulated that schizophrenia represents a disorder of
      anomalous cerebral lateralization. This study is a replication of earlier
      preliminary findings using a multichannel neuromagnetometer, suggesting altered
      lateralization in schizophrenia in male subjects, with an extension of the
      findings to female subjects. METHODS: We used magnetoencephalography-based
      magnetic source imaging to estimate the intracranial location of the 100
      millisecond latency auditory-evoked field component (M100) in both left and right
      hemispheres of 20 patients with paranoid schizophrenia and 20 controls without
      schizophrenia. Neuroanatomical data were obtained by means of magnetic resonance
      imaging, from which we segmented and computed volumes of both total brain and
      left and right superior temporal gyri. RESULTS: Locations of M100 source were
      compatible with neuronal generators located in the transverse gyri of Heschl on
      the superior temporal gyri in both study groups; M100 sources were asymmetric in
      all the control subjects. The male patient subgroup exhibited significantly less
      asymmetry than the control group, while the female patient subgroup actually
      showed significantly more asymmetry. The male patient subgroup generally had
      smaller superior temporal gyri than the control group. No evidence of total brain
      volume differences was observed. CONCLUSIONS: Our findings support previous
      magnetoencephalography-based studies suggesting anomalous cerebral lateralization
      in schizophrenia. Further, in extending our studies to female patients, our data
      suggest that the nature of this anomaly is sex specific, a finding that, to our
      knowledge, has not previously been reported.

PMID- 9152098
TI  - Psychotic exacerbations and enhanced vasopressin secretion in schizophrenic
      patients with hyponatremia and polydipsia.
AB  - BACKGROUND: For unclear reasons, life-threatening water intoxication often
      coincides with acute psychosis in polydipsic schizophrenic patients with chronic
      hyponatremia. In contrast, most polydipsic schizophrenic patients are
      normonatremic and never manifest hyponatremia. To explore whether the effect of
      acute psychosis on water balance differs in these 2 schizophrenic subgroups, we
      compared their responses to drug-induced psychotic exacerbations. METHODS:
      Matched polydipsic schizophrenic patients with (n = 6) and without (n = 8)
      hyponatremia were identified based on past and current indexes of fluid intake
      and hydration. A transient psychotic exacerbation was induced with an infusion of
      the psychotomimetic methylphenidate hydrochloride (0.5 mg/kg of body weight over
      a 60-second period). Antidiuretic hormone levels, subjective desire for water,
      and factors known to influence water balance were measured at 15-minute intervals
      for 2 hours. RESULTS: Except for the expected differences in plasma osmolality
      and sodium, basal measures were similar in the 2 groups. Following
      methylphenidate administration, antidiuretic hormone levels increased more in the
      hyponatremic patients (P < .02), despite their consistently lower plasma
      osmolality (P < .007). No known or putative antidiuretic hormone stimulus could
      account for this finding. Only basal positive psychotic symptoms (P < .09) and
      plasma sodium (P < .18) were even marginally associated with the peak
      antidiuretic hormone responses, but neither factor could explain the difference
      in the response by the 2 groups. CONCLUSION: Psychotic exacerbations are
      associated with enhanced antidiuretic hormone secretion, for unknown reasons, in
      schizophrenic patients with hyponatremia and polydipsia, thereby placing them at
      increased risk of life-threatening water intoxication.

PMID- 9152100
TI  - Backward masking performance in unaffected siblings of schizophrenic patients.
      Evidence for a vulnerability indicator.
AB  - BACKGROUND: Visual masking is a procedure that is used to assess the earliest
      components of visual processing. In backward masking, the identification of an
      initial stimulus (the target) is disrupted by a later stimulus (the mask). The
      masking function can be divided into an early component (e.g., up to about 60 ms)
      that reflects the involvement of sensory-perceptual processes, and a later
      component that reflects susceptibility to attentional disengagement as the mask
      diverts processing away from the representation of the target. Schizophrenic
      patients show anomalies on both masking components. It is not known whether
      backward masking deficits reflect enduring genetic vulnerability to
      schizophrenia. METHODS: We assessed 32 unaffected siblings of schizophrenic
      patients and 52 normal control subjects on the early and late components of 4
      masking conditions. The conditions differentially involved the sustained and
      transient visual pathways. RESULTS: The unaffected siblings showed poorer overall
      performance than control subjects on the masking procedures. More specifically,
      siblings showed anomalies on the early, sensory-perceptual component, but not on
      the later, attentional disengagement component. CONCLUSIONS: The backward masking
      performance deficits that have been observed in schizophrenic patients appear to
      reflect enduring vulnerability to the disorder rather than only the symptoms of
      the illness. This vulnerability appears to be associated with early, sensory
      perceptual processes.

PMID- 9152099
TI  - Relapse and rehospitalization during maintenance treatment of schizophrenia. The
      effects of dose reduction and family treatment.
AB  - BACKGROUND: Previous studies have examined dose reduction and family treatment in
      schizophrenia, but none has examined their interaction. This study assessed the
      impact of dose reduction of antipsychotic medication and family treatment on
      relapse and rehospitalization during maintenance treatment. METHODS: Subjects
      were 313 male and female outpatients at 5 centers with a DSM-III-R diagnosis of
      schizophrenia or schizoaffective disorder. In a 3 x 2 design, subjects were
      randomized to 1 of 3 medication strategies using fluphenazine decanoate under
      double-blind conditions: continuous moderate dose (standard) (12.5-50 mg every 2
      weeks); continuous low dose (2.5-10 mg every 2 weeks); or targeted, early
      intervention (fluphenazine only when symptomatic). Subjects also were randomized
      to 1 of 2 family treatment strategies (supportive or applied). Supportive family
      management involved monthly group meetings. The more intensive applied family
      management involved monthly group meetings and home visits where communication
      and problem-solving skills were taught. Patients and families were treated and
      assessed for 2 years. RESULTS: Both continuous low-dose and targeted treatment
      increased use of rescue medication and relapse; only targeted treatment increased
      rehospitalization. This pattern was consistent across both family treatments;
      there were no differences between family treatments. CONCLUSIONS: These findings
      reaffirm the value of antipsychotic medication in preventing relapse and
      rehospitalization. The absence of family treatment differences may be because
      both conditions engaged families.

PMID- 9152102
TI  - The brain metabolic patterns of clozapine- and fluphenazine-treated patients with
      schizophrenia during a continuous performance task.
AB  - BACKGROUND: The comparison of the effects of 2 classes of neuroleptic drugs on
      regional brain functional activities may reveal common mechanisms of
      antipsychotic drug efficacy. METHODS: The regional cerebral glucose metabolic
      rates of patients with schizophrenia who were and were not receiving neuroleptic
      drugs and normal control subjects were obtained by positron emission tomography
      using fludeoxyglucose F 18 as the tracer. RESULTS: Compared with normal controls
      and patients not receiving medication, fluphenazine hydrochloride- and clozapine
      treated patients had lower global gray matter absolute metabolic rates throughout
      the cortex. When normalized regional glucose metabolic rates were examined, both
      medications lowered rates in the superior prefrontal cortex and increased rates
      in the limbic cortex. Fluphenazine, but not clozapine, increased metabolic rates
      in the subcortical and lateral temporal lobes, whereas clozapine, but not
      fluphenazine, decreased inferior prefrontal cortex activity. CONCLUSIONS: These
      changes are consistent with the idea that neuroleptic drugs lead to
      "compensation" and "adaptation" rather than "normalization" of the functional
      activities of brain structures in schizophrenia. The overall similarity of their
      global and regional metabolic effects suggests that both classes of antipsychotic
      drugs share some common mechanisms of action. One possibility is that of inducing
      a shift in the balance of cortical to limbic cortex activity. Differential
      effects in the inferior prefrontal cortex and the basal ganglia might underlie
      differences in the therapeutic efficacy and side effect profile of clozapine and
      fluphenazine.

PMID- 9152101
TI  - Thought disorder in schizophrenic and control adoptees and their relatives.
AB  - BACKGROUND: Previous research showed significantly elevated levels of thought
      disorder in the relatives of persons with schizophrenia, as well as in the
      persons with schizophrenia themselves. Comparisons of schizophrenic and control
      adoptees and their respective relatives provide a method for minimizing the
      confounding of genetic and environmental sources of familial resemblance and for
      elucidating whether the elevated levels of thought disorder in persons with
      schizophrenia and their relatives reflect the influence of shared genetic
      factors, shared environmental factors, or both. The present study provides the
      first such adoption-sample data on an operationally defined measure of thought
      disorder. METHODS: Speech samples elicited by standard interview questions from
      schizophrenic and control adoptees and their respective biological and adoptive
      relatives were tape-recorded. Verbatim transcripts of these speech samples were
      scored, while unaware of the personal or family diagnoses of the subjects, using
      the Thought Disorder Index (TDI). RESULTS: The mean TDI scores were significantly
      higher in schizophrenic than in control adoptees and in biological relatives of
      the schizophrenic adoptees than in the biological relatives of the control
      adoptees, whereas the respective groups of adoptive relatives did not differ
      significantly. The differences were most marked for the samples of biological
      sibs and half sibs, which were larger and more representative than the samples of
      parents. CONCLUSION: Results suggest that the elevated TDI scores in the
      relatives of persons with schizophrenia that have been found in other studies
      reflect the operation of genes increasing the liability for schizophrenia, rather
      than the rearing experiences that were shared in common with schizophrenic
      probands.

PMID- 9152103
TI  - Increased phospholipid breakdown in schizophrenia. Evidence for the involvement
      of a calcium-independent phospholipase A2.
AB  - BACKGROUND: Magnetic resonance spectroscopy studies have suggested above-normal
      turnover of membrane phospholipids in brains of patients with schizophrenia. One
      possible explanation for these findings is increased activity of the phospholipid
      catabolizing enzyme phospholipase A2 (PLA2). However, attempts to demonstrate
      higher PLA2 activity in the serum of subjects with schizophrenia have led to
      conflicting results. We hypothesized that this was due to serum PLA2 activity
      consisting of a family of different enzymes, with each group of investigators
      measuring activity of different PLA2 forms. DESIGN: Activity of PLA2 in serum
      samples obtained from 24 individuals with schizophrenia was compared with serum
      obtained from 33 age- and sex-matched control subjects, using both fluorometric
      and radiometric assays with different substrates. Each method had previously
      yielded conflicting results concerning the status of the enzyme in schizophrenia.
      RESULTS: With the fluorometric assay, serum PLA2 activity in individuals with
      schizophrenia was markedly increased by 49% compared with control subjects (P <
      .001). In contrast, radiometric assay of the same serum samples resulted in PLA2
      activity not significantly different between patients and control subjects.
      Further investigations demonstrated that, whereas the radiometric assay measured
      activity of a calcium-dependent enzyme, the fluorometric assay detected a calcium
      insensitive enzyme possessing an acid-neutral pH optimum. CONCLUSIONS: Increased
      calcium-independent PLA2 activity was seen in the serum of patients with
      schizophrenia. This change, if present also in the brain, may well explain the
      increased levels of phosphodiesters observed using magnetic resonance
      spectroscopy and therefore may contribute to the pathophysiological features of
      the disorder.

PMID- 9152105
TI  - Physician-assisted suicide.

PMID- 9152104
TI  - Unusual cause of dysarthria in a patient with cerebrovascular disease.

PMID- 9152106
TI  - To be or not to be? That is the question facing many neurology residency
      programs.

PMID- 9152107
TI  - Diagnostic criteria for genetic studies of Tourette syndrome.

PMID- 9152108
TI  - Lou Gehrig and amyotrophic lateral sclerosis. Is vitamin E to be revisited?
AB  - Investigators are beginning to reexamine the use of vitamin E for the treatment
      of amyotrophic lateral sclerosis. Vitamin E was isolated in the 1920s, and the
      results of animal studies led rapidly to clinical use. Regrettably, vitamin E did
      not ameliorate the progression of amyotrophic lateral sclerosis for Lou Gehrig,
      but more recent advances may identify subpopulations that do respond to vitamin
      E.

PMID- 9152109
TI  - Treatment of depression improves adherence to interferon beta-1b therapy for
      multiple sclerosis.
AB  - OBJECTIVES: To examine the relationship between patient-reported depression and
      adherence to therapy with interferon beta-1b (IFN beta-1b) and to test the
      hypothesis that treatment of depression is associated with improved adherence.
      DESIGN: Patients with multiple sclerosis were followed up 6 months after
      initiating therapy with IFN beta-1b. SETTING: A university outpatient multiple
      sclerosis center, an academic group practice, and a health maintenance
      organization. PATIENTS: Eighty-five patients with clinically evident multiple
      sclerosis taking IFN beta-1b. MAIN OUTCOME MEASURE: Follow-up questionnaire.
      RESULTS: Thirty-five (41%) of the 85 patients reported new or increased
      depression within 6 months of initiating therapy with IFN beta-1b. Patients
      experiencing symptoms of depression were more likely to discontinue therapy.
      Among the patients reporting new or increased depression, 86% who received
      psychotherapy or antidepressant medication and 38% of the patients who received
      no therapy for depression continued the IFN beta-1b therapy (P = .003). Although
      psychotherapy was used as a treatment option more frequently in university and
      academic group practice-based multiple sclerosis clinics than in the health
      maintenance organization (P = .02), the treatment adherence patterns were similar
      across sites. CONCLUSIONS: These findings support previous findings that patients
      report increased depression after initiating therapy with IFN beta-1b. Although
      the source of this depression is unclear, these findings suggest that treating
      patient-reported depression increases adherence to treatment.

PMID- 9152110
TI  - Clinical characteristics of a chromosome 17-linked rapidly progressive familial
      frontotemporal dementia.
AB  - OBJECTIVE: To describe symptoms, signs, neuroimaging results, and neuropathologic
      findings in patients from a family with chromosome 17q21-linked autosomal
      dominant frontotemporal dementia. DESIGN: Multiple case report with genetic
      investigations. SUBJECTS: The disease was observed in a Swedish family and
      documented in 3 generations. Four siblings are described in this article.
      RESULTS: A rapidly progressive dementia with genetic linkage to chromosome 17q21
      was observed. The mean age of onset was 51 years and the average duration of
      disease to death was 3 years. Two patients started with speech disturbances
      leading to a progressive, nonfluent aphasia, 1 patient had onset symptoms of leg
      apraxia and akinesia and muscular rigidity, and in 1 patient reckless driving was
      the first symptom. Loss of spontaneous speech developed later in all patients and
      emotional bluntness in 3 of the patients. Cerebral perfusion was decreased in the
      frontal areas in all patients. In the person with apraxia as the onset symptom,
      the cerebral blood flow was also diminished in the left hemisphere, where a
      slight atrophy was detected on magnetic resonance imaging scans. At the
      postmortem examination, slight gliosis of the parietal lobes was observed in this
      patient. In all patients there was a frontocentral degeneration of the cortex
      with discrete microvacuolation and gliosis. CONCLUSION: Clinical features of
      frontotemporal dementia, parkinsonism, an early age of onset, a rapid disease
      progression, and variable onset symptoms were seen in these patients. Two other
      clinically distinct diseases, dementia with pallido-ponto-nigral degeneration and
      a disinhibition-dementia-parkinsonism-amyotrophy complex, have recently been
      mapped to chromosome 17q21. In the family described in this article, genetic
      linkage was detected to the same region, suggesting the possibility that these
      diseases may originate from pathogenic mutations in the same gene.

PMID- 9152111
TI  - Simulated car crashes and crash predictors in drivers with Alzheimer disease.
AB  - BACKGROUND: Alzheimer disease (AD) is the most common cause of dementia and can
      impair cognitive abilities crucial to the task of driving. Rational decisions
      about whether such impaired individuals should continue to drive require
      objective assessments of driver performance. OBJECTIVE: To measure relevant
      performance factors using high-fidelity driving simulation. DESIGN: We examined
      the effect of AD on driver collision avoidance using the Iowa Driving Simulator,
      which provided a high-fidelity, closely controlled environment in which to
      observe serious errors by at-risk drivers. We determined how such unsafe events
      are predicted by visual and cognitive factors sensitive to decline in aging and
      AD. SETTING: The University of Iowa Hospitals and Clinics, Iowa City, and the
      Iowa Driving Simulator. PARTICIPANTS: Thirty-nine licensed drivers: 21 with AD
      and 18 controls without dementia. MAIN OUTCOME MEASURES: We determined the number
      of crashes and related performance errors and analyzed how these occurrences were
      predicted by visual and cognitive factors. RESULTS: Six participants (29%) with
      AD experienced crashes vs 0 of 18 control participants (P = .022). Drivers with
      AD were more than twice as likely to experience close calls (P = .042). Plots of
      critical control factors in the moments preceding a crash revealed patterns of
      driver in-attention and error. Strong predictors of crashes included visuospatial
      impairment, reduction in the useful field of view, and reduced perception of 3
      dimensional structure-from-motion. CONCLUSIONS: High-fidelity driving simulation
      provides a unique new source of performance parameters to standardize the
      assessment of driver fitness. Detailed observations of crashes and other safety
      errors provide unbiased evidence to aid in the difficult clinical decision of
      whether older or medically impaired individuals should continue to drive. The
      findings are complementary to evidence currently being gathered using techniques
      from epidemiology and cognitive neuroscience.

PMID- 9152112
TI  - Recurrent supratentorial malignant gliomas in children. Long-term salvage therapy
      with oral etoposide.
AB  - BACKGROUND: A long-term regimen of oral etoposide, a type of chemotherapy, is
      used in oncology and is effective in treating germ-cell tumors, lymphomas, Kaposi
      sarcoma, and primary brain tumors. OBJECTIVE: To examine the toxic effects and
      efficacy of long-term salvage chemotherapy using oral etoposide. PATIENTS AND
      METHODS: Fourteen children (8 boys and 6 girls) with recurrent supratentorial
      gliomas, ranging in age from 4 to 18 years (median age, 9 years), were treated
      with etoposide. Tumor histologic grades included Daumas-Duport grade 3 (10
      children) and grade 4 astrocytomas (4 children). All children had been treated
      previously with radiotherapy (median dose, 60 Gy) and nitrosourea-based
      chemotherapy. Each cycle of therapy consisted of 21 days of etoposide (50 mg/m2
      daily) followed by a 14-day period of rest and an additional 21 days of etoposide
      (50 mg/m2 daily). Measurements of complete blood cell counts were taken biweekly.
      A neurological examination and a magnetic resonance image of the brain with
      contrast medium were performed before each cycle of therapy. RESULTS: Treatment
      related complications included the following partial alopecia (8 children);
      diarrhea (6 children); weight loss (4 children); anemia (4 children); neutropenia
      (4 children) and thrombocytopenia (4 children). Four children required
      transfusion (4 with packed red blood cells and 3 with platelets) and 2 children
      received antibiotic therapy for neutropenic fever. There were no treatment
      related deaths. All children were examined for response. In 7 children (50%), the
      results of magnetic resonance imaging indicated either a partial response (3
      children) or stable disease (4 children), with a median duration of response of 8
      months. CONCLUSION: Oral etoposide is a well tolerated and relatively nontoxic
      chemotherapeutic agent with demonstrated activity in children with recurrent
      supratentorial gliomas.

PMID- 9152114
TI  - Neuromuscular blocking drugs do not alter the pupillary light reflex of
      anesthetized humans.
AB  - OBJECTIVE: To test the hypothesis that systemically administered neuromuscular
      blocking drugs acutely alter resting pupil size or the direct reflex response to
      light in anesthetized humans. DESIGN: Patients were randomized to receive an
      intravenous injection of saline (0.15 mL/kg), pancuronium bromide (0.1 mg/kg), or
      vecuronium bromide (0.15 mg/kg) after induction of general anesthesia and
      tracheal intubation. SETTING: The University of California, San Francisco,
      Moffitt-Long Hospitals. PATIENTS: Healthy adults (American Society of
      Anesthesiologists physical status I or II) of either sex scheduled for elective
      surgery requiring general anesthesia, tracheal intubation, and muscle relaxation
      of an anticipated duration of 2 or more hours. MAIN OUTCOME MEASURES:
      Measurements of resting pupil size, direct reflex response to light, and
      constriction velocity were obtained in double-blinded fashion using infrared
      pupillometry. RESULTS: Pupillary size, reflex amplitude, and constriction
      velocity were not altered by the presence of either vecuronium or pancuronium.
      Tetanic stimuli and concomitant isoflurane administration respectively increased
      and decreased pupillary light reflex amplitude, indicating that pupillary
      responses were not fixed. CONCLUSIONS: We conclude that systemically administered
      neuromuscular blocking drugs (vecuronium and pancuronium) do not acutely affect
      the pupillary light reflex in healthy, anesthetized patients.

PMID- 9152113
TI  - A positron emission tomographic study of impaired word recognition and
      phonological processing in dyslexic men.
AB  - BACKGROUND: Developmental dyslexia is characterized by impaired word recognition,
      which is thought to result from deficits in phonological processing. Improvements
      during the course of development are thought to disproportionately involve
      orthographic components of reading; phonological deficits persist into adulthood.
      OBJECTIVE: To localize the neural correlates of impaired word recognition and
      phonological processing in men with developmental dyslexia. METHODS: Regional
      cerebral blood flow was measured with oxygen 15 positron emission tomography in
      17 men with dyslexia and in 14 matched controls during the performance of
      phonological and orthographic tasks--pronunciation (reading aloud) and lexical
      decision making--designed to activate posterior and anterior perisylvian
      cortices, respectively. RESULTS: Altered patterns of activation (reduced
      activation, unusual deactivation) were seen in dyslexic men in mid- to posterior
      temporal cortex bilaterally and in inferior parietal cortex, predominantly on the
      left, during both pronunciation and decision making. In contrast, dyslexic men
      demonstrated essentially normal activation of left inferior frontal cortex during
      both phonological and orthographic decision making. CONCLUSION: These, along with
      prior findings, are compatible with a hypothesis of bilateral involvement of
      posterior temporal and parietal cortices in dyslexia.

PMID- 9152115
TI  - Localized proton magnetic resonance spectroscopy in patients with adult
      adrenoleukodystrophy. Increase of choline compounds in normal appearing white
      matter.
AB  - OBJECTIVES: To describe the changes in the results of magnetic resonance imaging
      and spectroscopy occurring in the normal-appearing white matter of patients with
      adult adrenoleukodystrophy and to present evidence of a particular change that
      may serve as a marker for the follow-up of the disease. DESIGN: Neurologic,
      magnetic resonance imaging, and localized proton spectroscopic examinations were
      performed in 11 patients with adult adrenoleukodystrophy and compared with 11 sex
      and age-matched controls. PATIENTS: Eleven patients with adult
      adrenoleukodystrophy participated in a trial of dietary therapy with glyceryl
      trioleate and glyceryl trierucate (Lorenzo's oil) in the Federation de Neurologie
      and the Institut National de la Sante et de la Recherche Medicale, Unite 134, at
      the Hopital de la Salpetriere in Paris, France. RESULTS: The results of magnetic
      resonance imaging of the white matter were normal in 2 patients and showed areas
      of mild symmetrical hypersignals on T2-weighted images and fluid attenuated
      inversion recovery sequences, localized in the posterior white matter in 9
      patients. The results of spectroscopy indicated that the peak of the area of
      choline-containing compounds was increased at long echo times in patients with
      adult adrenoleukodystrophy, which may reflect very long-chain fatty acid
      accumulation in this disease. The peak of the area of myo-inositol-containing
      compounds was increased at short echo times in patients with adult
      adrenoleukodystrophy, which may indicate a rise in this metabolite concentration.
      The N-acetylaspartate-creatine amplitude ratio was significantly decreased in
      patients with motor deficit. The significance of this finding remains to be
      established. CONCLUSIONS: The results of localized proton magnetic resonance
      spectroscopy show abnormalities in the cerebral white matter of patients with
      adult adrenoleukodystrophy, which may contribute to the understanding of the
      pathophysiologic characteristics of the disease. Although changes in the results
      of spectroscopy found in this disease are not specific, the increase of choline
      containing compounds may reflect the accumulation of very long-chain fatty acids
      in the central nervous system. Localized proton magnetic resonance spectroscopy
      may prove a valuable technique, in addition to magnetic resonance imaging, for
      noninvasive investigation of patients with adult adrenoleukodystrophy undergoing
      future clinical trials.

PMID- 9152117
TI  - Does modification of the Innsbruck and the Glasgow Coma Scales improve their
      ability to predict functional outcome?
AB  - BACKGROUND: The accurate prediction of functional outcome requires the
      development of multivariate models. To enhance their contribution to such models,
      the predictive power of each component must be optimized. OBJECTIVES: To improve
      the predictive power of coma scales as the first step in building more
      sophisticated multivariate models to predict specific levels of functional
      outcome. DESIGN: Prospective descriptive study. SETTING: Neurology and
      neurosurgery intensive care unit (NNICU) in a tertiary care academic center.
      PATIENTS: Eighty-four patients with acute traumatic brain injury, intracerebral
      hemorrhage, subarachnoid hemorrhage, or ischemic stroke. INTERVENTIONS: None.
      MAIN OUTCOME MEASURES: The Glasgow Coma Scale (GCS) and Innsbruck Coma Scale
      (ICS) were administered within 24 hours of admission to the NNICU and then at 48
      hour intervals until discharge of the patient from the NNICU. The assessments
      were performed by 3 occupational therapy graduate students working under the
      supervision of the medical director of the NNICU. The functional outcome at 3
      months after discharge from the hospital was assessed by telephone by the same
      nurse using the following categories: (1) dead, (2) receiving nursing home or
      custodial care, (3) home with help, or (4) independent. Cronbach's alpha
      estimates of reliability for each scale were computed using all scores obtained
      during the study. The analyses indicated that the verbal response item of the GCS
      and the oral automatisms item of the ICS were less reliable in this patient
      population. The scales were modified by deleting those items, and predictive
      validity for the original and modified scales was computed using a discriminant
      function of the admission scores. RESULTS: Before modification, both scales were
      best at predicting independence (GCS and ICS, 71% correct) and mortality (GCS,
      60% correct; ICS, 56% correct). The modifications produced a modest improvement
      in the ability of both scales to better predict levels of outcome (modified GCS:
      home with help, 33% correct, independent, 71% correct; modified ICS: home with
      help, 0% correct, independent, 74% correct). CONCLUSIONS: By deleting items with
      low reliability from the ICS and the GCS we achieved improved reliability and
      predictive validity. The improvement in predictive power, however, was inadequate
      to accurately predict functional outcome. Combining clinical scales with other
      demographic, physiological, functional, and radiographic data will be needed to
      achieve useful predictions of functional outcome.

PMID- 9152116
TI  - Tiagabine therapy for complex partial seizures. A dose-frequency study. The
      Tiagabine Study Group.
AB  - OBJECTIVE: To evaluate the efficacy and safety of 2 regimens of tiagabine as add
      on therapy for patients with complex partial seizures (CPSs) that are refractory
      to other treatment. DESIGN: Randomized, double-blind, placebo-controlled, add-on,
      parallel-group trial with an 8-week baseline period, 12-week experimental period
      (4 weeks of dose titration and 8 weeks of fixed-dose therapy), and 4-week
      termination period. SETTING: Twenty-six centers throughout the United States.
      PATIENTS: Three hundred fifty-one patients were enrolled, 318 were entered in the
      double-blind period, and 271 completed the study. INTERVENTIONS: Tiagabine, 16 mg
      2 times per day (106 patients); tiagabine, 8 mg 4 times daily (105 patients); and
      placebo (107 patients). The doses of tiagabine were titrated in 3 steps to the
      fixed dose. MAIN OUTCOME MEASURE: The median change in the 4-week rate of CPSs
      from baseline to experimental period. RESULTS: The median change from baseline
      was -1.6 CPSs per 4 weeks in the group of patients who were given tiagabine 2
      times per day, and it was -1.2 CPSs in the group of patients who were given
      tiagabine 4 time per day (P = .06 and P = .02, respectively, compared with
      placebo). The 4-week seizure frequency was reduced by 50% or more in 31% of the
      patients who were given tiagabine 2 times per day and in 27% of the patients who
      were given tiagabine 4 times per day vs 10% of the placebo-treated patients (P <
      or = .001 for each tiagabine-treated group compared with the placebo group). The
      most frequent adverse events involved the central nervous system and occurred in
      comparable proportions in the 3 treatment groups. Similar proportions of patients
      discontinued the study prematurely for adverse events. CONCLUSIONS: Tiagabine
      administered 2 and 4 times daily as add-on pharmacotherapy was effective in
      reducing CPSs in patients with epilepsy whose conditions were refractory to
      treatment with other antiepileptic agents, and it was well tolerated.

PMID- 9152118
TI  - Neuroanatomical substrates of late-life minor depression. A quantitative magnetic
      resonance imaging study.
AB  - OBJECTIVE: To examine the neuroanatomical correlates of late-life minor
      depression using magnetic resonance imaging. DESIGN: Cross-sectional quantitative
      magnetic resonance imaging study of elderly patients with minor depression and
      age-matched controls. SETTING: Patients and controls were recruited from the
      community through advertisements to the Section of Geriatric Psychiatry,
      University of Pennsylvania, Philadelphia. PARTICIPANTS: Our sample included 18
      subjects diagnosed as having minor depression using the modified Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition, research criteria and 31
      controls without depression. Patients were free of other central nervous system
      disease and both groups had comparable degrees of medical comorbidity. MAIN
      OUTCOME MEASURES: All images were acquired on a 1.5-T scanner and absolute and
      normalized quantitative measures of global and focal brain and cerebrospinal
      fluid volumes were compared between groups. RESULTS: Prefrontal lobe volume was
      significantly smaller in the group with minor depression (P = .002) compared with
      controls after controlling for age, sex, and age by sex interactions. More global
      measures of brain and cerebrospinal fluid volumes were comparable in both groups.
      CONCLUSIONS: These data suggest that focal prefrontal atrophy may provide an
      important neuroanatomical substrate in late-life minor depression.

PMID- 9152119
TI  - Influence of peripheral nerve stimulation on human motor cortical excitability in
      patients with ventrolateral thalamic lesion.
AB  - OBJECTIVE: To determine the peripheral afferent pathways that influence the
      activities of the motor cortex by examining the effects of peripheral nerve
      stimulation on motor cortical excitability. PATIENTS AND METHODS: We examined 12
      healthy volunteers and 4 patients with localized brain lesions caused by
      cerebrovascular attack. Of the 4 patients, 1 patient had pontine infarction,
      including medial lemniscus, and severe sensory deficit and 3 had small localized
      lesions in the lateral part of the thalamus and neither sensory impairment nor
      abnormal N20 waves on somatosensory evoked potential recordings. Central motor
      tract excitability was examined by measuring a change in the motor evoked
      potential (MEP), using transcranial magnetic stimulation of the motor cortex
      after peripheral nerve stimulation at the wrist significantly increased MEP
      response in the controls at long conditioning-test intervals of 28 to 60
      milliseconds, as well as at short intervals of 0 to 6 milliseconds. A late MEP
      potentiation was not observed on the affected side in all patients. CONCLUSIONS:
      The loss of late MEP potentiation in patients with pontine and thalamic lesions
      indicates that this potentiation is caused by the alternation of the motor
      cortical excitability. Furthermore, the results in the patients with thalamic
      lesions suggest that the lateral nuclei of the thalamus, other than the ventral
      posterolateral nucleus and probably including the ventrolateral nucleus, have an
      important function in the processing of peripheral sensory input for tuning motor
      cortical excitability.

PMID- 9152120
TI  - Risk factors for depression in Parkinson disease.
AB  - OBJECTIVE: To evaluate whether depression in Parkinson disease (PD) is more
      closely related to the underlying neuropathological process or to environmental
      and psychological factors by correlating depression in PD with various clinical
      and demographic variables. DESIGN: Major depression, level of depressive symptoms
      as measured with the Montgomery-Aasberg Depression Rating Scale (MADRS), and
      clinical characteristics were investigated in a community-based cross-sectional
      study of carefully diagnosed patients with PD. Both bivariate and multivariate
      correlation analyses were performed to investigate correlations and predictive
      values of possible risk factors for major depression and MADRS score in PD.
      SETTING: Depression among patients with PD derived from a prevalence study in the
      county of Rogaland, Norway. PATIENTS: Two hundred forty-five patients with PD.
      RESULTS: Impaired cognitive function and the presence of a thought disorder were
      significant predictors of major depression. A Mini-Mental State Examination sum
      score below 24 and level 2 or higher on the thought disorder subscale of the
      Unified Parkinson Disease Rating Scale increased the probability of major
      depression by a factor of 6.6 and 3.5, respectively. Higher MADRS scores were
      also associated with lower Mini-Mental State Examination score and higher thought
      disorder score. In addition, MADRS scores also correlated with more impairment in
      activities of daily living, presence of motor fluctuations, more evidence of
      atypical parkinsonism, higher daily doses of levodopa, and younger age on the day
      on which prevalence was determined. CONCLUSIONS: Most of the observations of this
      study favor the hypothesis that depression in PD is a primary consequence of
      brain dysfunction. Situational factors may, however, also contribute to mood
      changes in PD.

PMID- 9152121
TI  - The validity of the family history method for identifying Alzheimer disease.
AB  - OBJECTIVE: To examine the validity of the family history method for identifying
      Alzheimer disease (AD) by comparing family history and neuropathological
      diagnoses. METHODS: Seventy-seven former residents of the Jewish Home and
      Hospital for the Aged, New York, NY, with neuropathological evaluations on record
      were blindly assessed for the presence of dementia and, if present, the type of
      dementia through family informants by telephone interviews. The Alzheimer's
      Disease Risk Questionnaire was used to collect demographic information and screen
      for possible dementia. If dementia was suspected, the Dementia Questionnaire was
      administered to assess the course and type of dementia, i.e., primary progressive
      dementia (PPD, likely AD), multiple infarct dementia, mixed dementia (i.e., PPD
      and multiple infarct dementia), and other dementias based on the modified
      Diagnostic and Statistical Manual of Mental Disorders, Third Edition, criteria.
      RESULTS: Sixty (77.9%) of 77 elderly subjects were classified as having dementia
      and 17 (22.1%) were without dementia by family history evaluation. Of the 60
      elderly subjects with dementia, 57 (95%) were found at autopsy to have had
      neuropathological changes related to dementia. The sensitivity of the family
      history diagnosis for dementia with related neuropathological change was 0.84 (57
      of 68) and the specificity was 0.67 (6 of 9). Using family history information to
      differentiate the type of dementia, the sensitivity for definite or probable AD
      (with or without another condition) was 0.69 (36 of 51) and the specificity was
      0.73 (19 of 26). The majority (9 of 15) of patients testing false negative for
      PPD had a history of stroke associated with onset of memory changes, excluding a
      diagnosis of PPD. CONCLUSIONS: Identifying dementia, in general, and AD, in
      particular, has an acceptable sensitivity and specificity. As is true for direct
      clinical diagnosis, the major issue associated with misclassifying AD in a family
      history assessment is the masking effects of a coexisting non-AD dementia or
      dementia-related disorders, such as stroke. Including mixed cases, ie, PPD and
      multiple infarct dementia in estimates of the familial risk for AD can reduce the
      extent of underestimation of PPD.

PMID- 9152122
TI  - Cerebrospinal fluid levels of alpha-secretase-cleaved soluble amyloid precursor
      protein mirror cognition in a Swedish family with Alzheimer disease and a gene
      mutation.
AB  - OBJECTIVE: To explore the relationship between possible biological markers of
      Alzheimer disease that are related to amyloid metabolism and mental functions.
      PARTICIPANTS: Twelve individuals from a Swedish family with Alzheimer disease and
      a double mutation at codons 670/671 of the amyloid precursor protein gene
      participated in the study. DESIGN: Cerebrospinal fluid levels of alpha-secretase
      cleaved soluble amyloid precursor protein (alpha-sAPP), total sAPP, and amyloid
      beta-peptide were correlated with data on multiple cognitive functions that
      covered the whole range of human performance. SETTING: The Alzheimer's Disease
      Research Centre, Department of Clinical Neuroscience, Section of Geriatric
      Medicine, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden.
      RESULTS: There were highly significant linear correlations between low levels of
      alpha-sAPP and poor performance on neuropsychological tests that assessed
      intelligence, verbal and visuospatial functions, memory, and attention. Within
      the group of nonmutation carriers, significant correlations were also obtained
      between the levels of alpha-sAPP and cognitive functions. A less striking
      association was seen between the levels of total sAPP and cognition. No
      association was found between the levels of amyloid beta-peptide and cognition.
      CONCLUSIONS: The strong relationship between alpha-sAPP levels and cognition in
      both patients with Alzheimer disease and normal-aging persons may imply that
      alpha-sAPP is involved in basic protective brain processes. Alternatively, less
      amyloid beta-peptide amounts are produced, leading to diminished plaque
      formation, when alpha-sAPP is generated.

PMID- 9152123
TI  - Fulminating encephalopathy with perivenular demyelination and vacuolar myelopathy
      as the initial presentation of human immunodeficiency virus infection.
AB  - OBJECTIVE: To study the neuropathologic features in a case involving a 22-year
      old woman in whom a fulminating encephalopathy developed as the initial
      manifestation of human immunodeficiency virus (HIV) infection. DESIGN: Case
      report. SETTING: Tertiary care hospital. PATIENT: The patient presented with
      rapidly progressive mental status, changes, cranial nerve abnormalities, and
      quadriplegia, which led to her death 5 months later. Serologic tests for HIV were
      initially indeterminate on Western blot analysis but were positive 1 week later.
      METHODS: A complete autopsy, including examination of the brain and spinal cord,
      was performed. Paraffin-embedded sections of the brain and spinal cord were
      examined using standard histologic staining procedures and immunohistochemical
      techniques. RESULTS: Neuropathologic examination revealed discrete foci of
      perivenular demyelination disseminated throughout the brain and spinal cord, as
      well as severe vacuolar myelopathy. Lesions typical of HIV encephalitis were not
      present. Human immunodeficiency virus-infected monocytes and microglia were
      observed in the vicinity of, but not restricted to, the perivenular demyelinating
      lesions. No other infectious agents were identified. CONCLUSIONS: The patient's
      acute encephalopathy was most likely the direct result of a widespread
      demyelinating process resembling acute disseminated encephalomyelitis. We suggest
      that the perivenular demyelination may represent an autoimmune reaction, possibly
      due to a nonspecific viral infection, occurring in the setting of chronic
      immunosuppression secondary to HIV. Although less likely, we cannot exclude the
      possibility that HIV could have directly triggered an autoimmune response that
      caused the acute disseminated encephalomyelitis-like lesions.

PMID- 9152124
TI  - Herpes simplex virus in primary graft failure.
AB  - OBJECTIVE: To determine the frequency of herpes simplex virus type 1 (HSV-1) in
      primary corneal graft failures. METHODS: The clinical data submitted about all
      cases of corneal graft failure on file at the Armed Forces Institute of
      Pathology, Washington, DC, from the last 25 years (1970-1995) were evaluated.
      Cases that met the definition of primary graft failure were examined
      microscopically and analyzed using polymerase chain reaction (PCR) for the DNA of
      HSV-1. RESULTS: Three (2.8%) of the 106 cases of graft failure were primary graft
      failures. The DNA from 2 of the 3 corneal buttons was amplifiable by PCR analysis
      and results of the PCR analysis and Southern blotting were positive for HSV-1.
      None of the results of the PCR analysis and Southern blotting of the corneal
      buttons from the 3 graft failures occurring later than 30 days were positive for
      HSV-1. Results of the PCR analysis and Southern blotting indicated that 2 of 3
      corneal buttons in the control group of clinically suspected herpetic keratitis
      were positive for HSV-1. The cornea from the first case of primary graft failure
      showed acute inflammation with stromal necrosis. The cornea in the second case
      had loss of endothelium without inflammation. CONCLUSIONS: The finding of DNA
      from HSV-1 in corneal buttons from 2 cases of primary graft failure supports
      similar observations by Cleator et al and suggests that HSV-1 may be pathogenic
      in some cases of primary graft failure. A larger study is needed to determine if
      HSV-1 is a causative factor in primary graft failure.

PMID- 9152125
TI  - Detection of varicella-zoster virus DNA in keratectomy specimens by use of the
      polymerase chain reaction.
AB  - OBJECTIVE: To study the correlation of clinical findings, histopathologic
      features, and detection of varicella-zoster virus (VZV) DNA in keratectomy
      specimens. MATERIALS AND METHODS: Fourteen corneal buttons from patients with a
      confirmed history of herpes zoster ophthalmicus were examined by use of light
      microscopy and the polymerase chain reaction. The polymerase chain reaction
      techniques included gel electrophoresis and hybridization for the detection of
      VZV DNA. RESULTS: Seven (50%) of the 14 specimens were positive for VZV DNA. The
      positive findings in the specimens correlated with the clinical findings of
      uveitis (3/3) and the histopathologic features of chronic stromal keratitis
      (4/4). Patients with stromal scarring, granulomatous keratitis, and neurotrophic
      ulcers had negative findings. The largest interval between the initial appearance
      and detection of viral DNA was 51 years. CONCLUSIONS: The results suggest that
      VZV DNA is not detectable in the cornea in every patient and at every stage of
      zoster keratitis. This may be due to the low number of VZV particles present in
      the cornea or the lack of viral DNA in the keratocytes. It remains unclear
      whether the VZV-related keratopathy is caused by an immunologic response to a
      viral antigen, the viable virus itself, or both.

PMID- 9152126
TI  - Laser treatment in subjects with high-risk clinical features of age-related
      macular degeneration. Posterior pole appearance and retinal function.
AB  - OBJECTIVES: To verify that a few laser lesions in the posterior pole can cause
      drusen to resolve in patients with age-related macular degeneration, and to
      document central retinal sensitivity as drusen resolve. DESIGN: In a pilot study,
      12 patients considered to be at high risk for sight-threatening complications
      from age-related macular degeneration were treated with 12 argon laser lesions in
      the posterior pole, with review for 12 to 24 months. RESULTS: Choroidal
      neovascularization developed in 1 patient 8 months after treatment, with
      consequent loss of central vision. In 9 of the remaining 11 patients, high-risk
      characteristics of drusen were reduced. Four patients had retinal pigment
      epithelial depigmentation, and all maintained 20/40 visual acuity at 12 months.
      One patient lost 3 lines of vision due to geographic atrophy after 12 months.
      Scotopic retinal threshold was elevated before treatment in 8 patients, compared
      with an age-matched comparison group. Of these, 4 patients underwent retesting 3
      to 6 months after treatment, and all had improved thresholds, but only 1 patient
      sustained the improvement at 12 months. At 12 months, 3 of the 8 patients showed
      an improvement in their mean retinal threshold. Of those in whom the mean retinal
      threshold worsened, the mean elevation in threshold was not more than 0.6 log
      units. CONCLUSIONS: A few laser lesions in the posterior pole leads to resolution
      of drusen. There does not appear to be an increased risk for choroidal
      neovascularization. Retinal threshold measurements show no indication of
      geographic atrophy at 1 year, but cannot be excluded as a late outcome. Laser
      treatment may reduce the risk for profound sight-threatening lesions in age
      related macular degeneration.

PMID- 9152127
TI  - Racial variation in retinopathy of prematurity. The Cryotherapy for Retinopathy
      of Prematurity Cooperative Group.
AB  - OBJECTIVES: To determine and compare the incidence of severe, vision-threatening
      retinopathy of prematurity (ROP) in black and white low-birth-weight infants.
      DESIGN: Prospective cohort study. SETTING: Seventy neonatal intensive care units
      in 23 US participating centers in the Multicenter Trial of Cryotherapy for
      Retinopathy of Prematurity. PATIENTS: A total of 4099 premature infants weighing
      less than 1251 g at birth were enrolled to evaluate the natural history of ROP.
      This 'Natural History' cohort included 2158 white infants and 1584 black infants
      who were followed up prospectively according to a Natural History protocol. MAIN
      OUTCOME MEASURES: Incidence and severity of acute ROP. RESULTS: While ROP
      occurred with similar frequency in all racial subgroups, severe ROP was less
      common in black infants. One hundred sixty (7.4%) of 2158 white infants reached
      threshold ROP (defined as at least 5 contiguous or 8 cumulative clock-hours of
      stage 3 retinopathy in zone 1 or zone 2 in the presence of "plus disease"
      [dilation and tortuosity of the posterior pole blood vessels]), but only 51
      (3.2%) of 1584 black infants progressed to threshold ROP. Using multiple logistic
      regression analysis, race emerged as a highly significant factor (P < .001) in
      the development of threshold disease, even when birth weight, gestational age
      status at delivery, sex, multiple births, and transport status were considered.
      CONCLUSIONS: Severe, vision-threatening ROP occurs with greater frequency in low
      birth-weight white infants than in low-birth-weight black infants who are
      seemingly at equivalent risk. The reason for this disparity is unknown. We
      speculate that differences in retinal pigmentation may confer relative protection
      against free radical-mediated phototoxic injury in black infants.

PMID- 9152128
TI  - In vivo fundus autofluorescence in macular dystrophies.
AB  - OBJECTIVE: To document the deviation from normal of fundus autofluorescence in
      patients with inherited macular dystrophies. METHODS: The intensity and spatial
      distribution of fundus autofluorescence was documented in 118 patients with
      inherited macular dystrophies by means of a confocal laser scanning
      ophthalmoscope, and the images were compared with the fundus appearance and
      fluorescein angiograms. RESULTS: Background autofluorescence appears to be
      elevated in all forms of macular dystrophies examined. The pale deposits at the
      level of the retinal pigment epithelium in disorders such as Best disease, adult
      vitelliform macular dystrophy, and fundus flavimaculatus were consistently
      associated with higher levels of autofluorescence than the background signal.
      There was no strong correlation between the intensity of autofluorescence and the
      fluorescein angiographic sign of a dark choroid. Increased levels of
      autofluorescence were present in a subject with a mutation known to cause macular
      dystrophy but in whom there were no manifest ophthalmoscopic or functional
      abnormalities. CONCLUSIONS: All dystrophies examined have in common accumulation
      of autofluorescent material in the retinal pigment epithelium to a greater degree
      than that seen with age. The abnormal high background autofluorescence associated
      with inherited macular dystrophies confirms the impression derived from
      histological studies that these disorders affect the entire retinal pigment
      epithelium. The lack of correlation between autofluorescence and the presence of
      a dark choroid implies that there may be different fluorophores in different
      disorders. The pale deposits at the level of the retinal pigment epithelium-Bruch
      membrane seen in macular dystrophies have similar autofluorescence
      characteristics. This technique may be useful in detecting the abnormal phenotype
      in early disease.

PMID- 9152129
TI  - Age-related macular disease in rural southern Italy.
AB  - OBJECTIVE: To report the prevalence of age-related maculopathy (ARM) in Salandra,
      a small, isolated southern Italian community, to test the hypothesis that an
      environmental factor, scarce in such a remote community but ubiquitous in modern
      industrial societies, might modify the risk of developing ARM. DESIGN: Population
      based cross-sectional survey. MAIN OUTCOME MEASURES: Prevalence of advanced age
      related macular degeneration (ARMD) (geographic atrophy or exudative maculopathy)
      and ARM (large, soft drusen or retinal pigment epithelium changes, or both)
      defined by fundus biomicroscopy and 30 degrees stereoscopic, macular photography.
      Self-sustenance was assessed by interview of participants and local shop
      retailers. The degree of genetic isolation was computed using a model that fits
      the genetic population structure with the frequency distribution of surnames in
      the community. RESULTS: A full ophthalmic examination was undertaken in 366
      (63.5%) of 576 eligible participants, 354 (96.7%) of whom had clinical or
      photographic assessment for the presence of ARMD and 310 (84.6%) of whom had
      drusen characteristics graded on color transparencies for ARM. The overall
      prevalence of ARMD was 1.1%. Drusen larger than 50 microns and more numerous than
      10 were found in 4.5% of subjects. Salandra was the birthplace of 87.2% of
      participants and for 77.3% of both parents of each subject. People in the
      community tended to consume homegrown products. CONCLUSION: The prevalence of ARM
      may be lower in this self-sustained farming community than elsewhere in the
      industrialized world.

PMID- 9152130
TI  - Optic nerve avulsion.
AB  - OBJECTIVE: To characterize the presentation, role of diagnostic imaging, and
      course in patients with optic nerve avulsion. METHODS: A retrospective review of
      medical records of all 6 patients with optic nerve avulsion who were seen at the
      Massachusetts Eye and Ear Infirmary, Boston, from January 1, 1991, to July 31,
      1995. RESULTS: The initial visual acuity ranged from 20/100 to no light
      perception. All 6 patients underwent neuroimaging, including computed tomography,
      magnetic resonance imaging, or both. B-scan ultrasonography was performed on 4
      patients, and the condition of 1 patient was evaluated with color Doppler
      ultrasonography to assess the optic nerve vasculature. In 1 patient, a computed
      tomographic scan was suggestive of an optic nerve avulsion. Neuroimaging in the
      other 5 patients, including 2 patients who underwent magnetic resonance imaging,
      failed to demonstrate an avulsion. During a follow-up period of up to 25 months,
      4 patients showed no improvement in visual acuity, 1 patient improved from no
      light perception to bare light perception, and 1 patient improved from 20/100 to
      20/25. CONCLUSIONS: These data suggest that final visual outcome was dependent on
      initial postinjury visual acuity. Neuroimaging, B-scans, and Doppler
      ultrasonography were usually not helpful in establishing the presence of optic
      nerve avulsion, although they may be useful in evaluating comorbid conditions.

PMID- 9152131
TI  - The role of blink adaptation in the pathophysiology of benign essential
      blepharospasm.
AB  - OBJECTIVE: To investigate eyelid movements in patients with benign essential
      blepharospasm (BEB), with an emphasis on the characterization of the kinematics
      of normal and spastic blinks, assessment of interocular differences, and further
      delineation of the role of adaptive blink mechanisms in eyelid movement
      disorders. PATIENTS AND METHODS: The electromagnetic search coil technique was
      used to record the metrics of blinks bilaterally in 5 patients with untreated
      BEB. Eyelid kinematics and the main-sequence (peak velocity vs amplitude)
      relationships were analyzed. RESULTS: Patients with BEB exhibited a decrease in
      blink amplitude and peak velocity. Moreover, the main-sequence slope was
      decreased bilaterally. Spasms were bilateral and relatively conjugate. There was
      no change in the coordination of normal blinking across the 2 eyelids.
      CONCLUSIONS: These data demonstrate the operation of the adaptive regulation of
      blinking in an eyelid movement disorder. The findings suggest that the adaptive
      regulation of blink is a bilateral event. Blink-adaptive control systems can act
      on the blink reflex excitability and main-sequence relationships, changing these
      either together or independently. The hyperexcitable blink reflex of BEB is met
      by what is believed to be an adaptive decrease in the main-sequence slope that
      would decrease the strength of debilitating spasms. Collectively, these data
      extend the knowledge of the pathophysiology of BEB and, perhaps more important,
      establish the role of blink system plasticity in eyelid movement disorders.

PMID- 9152132
TI  - HNK-1 epitope in the lens-ciliary zonular region in normal and pseudoexfoliative
      eyes. Immunohistochemistry and ultrastructure.
AB  - OBJECTIVE: To determine the specific binding sites for the HNK-1 adhesion
      molecule epitope in the lens-ciliary zonular region in normal and
      pseudoexfoliative (PSX) eyes. METHODS: Normal and PSX eyes and adjacent tissues
      from individuals aged 10 months to 89 years were investigated for the HNK-1
      epitope by immunohistochemistry and immunogold electron microscopy. RESULTS:
      Concentration of HNK-1 epitope was high in the anterior central lens capsule into
      old age, but it tapered earlier and progressively in the inner capsule and
      elsewhere. On zonular fibers, label was strongest at their lens and ciliary
      attachments and intense on related elastic microfibrils in adjacent ciliary
      stroma. Label was also strong on PSX fibers and above normal on PSX central
      capsule. In contrast, HNK-1 was absent on PSX aggregates in conjunctiva and skin
      and on normal elastic microfibrils in these tissues. CONCLUSIONS: The prominent
      HNK-1 epitope in lens capsule and zonule has age- and site-specific variations
      that favor adhesive roles in each. The high density of epitope on ocular PSX
      material suggests an aberrant increase in expression that may contribute to
      adhesiveness of these aggregates, HNK-1 negativity on extraocular elastic
      microfibrils and PSX aggregates indicates a unique difference in composition of
      intraocular and extraocular elastic tissue, of potential significance for ocular
      function in aging and lens-dislocating diseases.

PMID- 9152133
TI  - Retinal pigment epithelium abnormalities in mice with adenomatous polyposis coli
      gene disruption.
AB  - OBJECTIVE: To examine eyes from mice with targeted adenomatous polyposis coli
      (APC) gene disruption to determine if retinal pigment epithelium (RPE)
      abnormalities replicate the human counterpart. METHODS: Thirty-two eyes from 16
      mice heterozygous for APC gene disruption (chain-termination mutation in codon
      1638 of exon 15) and 12 control eyes were examined by light microscopy. RESULTS:
      Fifteen of 32 eyes from 12 of 16 APC-disrupted mice demonstrated abnormalities of
      the RPE and retina. The RPE abnormalities included RPE coloboma, unifocal and
      multifocal RPE hypertrophy, RPE hyperplasia, and RPE duplication with invasion in
      the areas of outer and inner segments. Retinal abnormalities included outer
      nuclear layer duplication and outer nuclear layer atrophy. There were no RPE and
      retinal abnormalities seen in the control eyes. CONCLUSIONS: This study is
      consistent with the hypothesis that the APC gene is critical in the regulation of
      RPE proliferation and development. These findings also demonstrate that mutation
      of the APC gene in codon 1638, a location beyond the previously described
      critical region for human RPE abnormalities, leads to perturbation in the mouse
      RPE and retina. Further study of this murine model and the APC/RPE relationship
      may provide insight into regulatory mechanisms for RPE proliferation.

PMID- 9152134
TI  - Identification of missense mutations in the Norrie disease gene associated with
      advanced retinopathy of prematurity.
AB  - BACKGROUND: Retinopathy of prematurity (ROP) is a retinal vascular disease
      occurring in infants with short gestational age and low birth weight and can lead
      to retinal detachment (ROP stages 4 and 5). X-linked familial exudative
      vitreoretinopathy is phenotypically similar to ROP and has been associated with
      mutations in the Norrie disease (ND) gene in some cases. OBJECTIVE: To determine
      if similar mutations in the ND gene may play a role in the development of
      advanced ROP. METHODS: Clinical examination and molecular genetic analysis were
      performed on 16 children, including 2 dizygotic and 1 monozygotic twin pairs, and
      their parents from 13 families. RESULTS: Sequencing of the amplified products
      revealed missense mutations (R121W and L108P) in the third exon of the ND gene in
      4 patients. These mutations were not present in an unaffected premature twin, 2
      children with regressed stage 3 ROP, the parents, or in 50 unrelated healthy
      control subjects. CONCLUSION: These findings suggest that mutations in the ND
      gene may play a role in the development of severe ROP in premature infants.

PMID- 9152136
TI  - The use of polymerase chain reaction techniques to detect varicella-zoster virus
      in corneal transplant tissue.

PMID- 9152135
TI  - Eye color changes past early childhood. The Louisville Twin Study.
AB  - OBJECTIVE: To determine whether eye color changes after 6 years of age. DESIGN:
      Longitudinal data on eye color were obtained from the Louisville Twin Study,
      Louisville, Ky. Twins (n = 1513 [individuals]) were assessed at least once and
      most twins (n = 1386) were examined on 2 or more occasions. Parents of twins were
      also examined at the study inception, 128 of whom were assessed again from
      February 1989 to October 1993. MAIN OUTCOME MEASURE: Eye color was assessed at
      each examination by matching the iridial coloration of the subject to 1 of 15
      painted glass eye anterior segments, similar to those in artificial eyes, mounted
      on a circular disk. The spectrum ranged from light blue (1) to dark brown (15).
      RESULTS: Among whites (n = 1359), the eye color of 3.8% to 8.6% of the sample
      twins became 2 U or more darker or 2 U or more lighter during 3- to 9-year
      intervals between 6 years of age and adulthood (> 18 years, < 24 years). Among
      identical (monozygotic) twin pairs, there was a high degree of concordance in eye
      color (r = 0.98 [P < .001]), while in fraternal (dizygotic) twin pairs, the
      concordance was less pronounced (r = 0.49) and decreased with age (r = 0.07).
      Among the sample of the mothers of twins, 9% had irides that lightened by 2 U or
      more during the follow-up period. CONCLUSION: Most individuals achieve stable eye
      color by 6 years of age. However, a subpopulation of 10% to 15% of white subjects
      have changes in eye color throughout adolescence and adulthood in the eye color
      range that can be expected to reflect changes in iridial melanin content or
      distribution. These data also suggest that such changes in eye color, or the
      propensity to such changes, may be genetically determined.

PMID- 9152137
TI  - Medical ethics and the excimer laser.

PMID- 9152138
TI  - Cystic epithelial downgrowth following clear-corneal cataract extraction.
AB  - Epithelial downgrowth is a serious complication of intraocular surgery. It is
      characterized by the diffuse or cystic proliferation of surface epithelium inside
      the eye. Advances in microsurgical technique that result in smaller surgical
      wounds and permit greater precision in wound closure should reduce the incidence
      of this complication. We report a case of epithelial downgrowth presenting 3
      years after an uncomplicated clear-corneal cataract extraction with insertion of
      a posterior chamber silicone lens. The epithelial down-growth was amenable to
      surgical correction because the well-defined cyst could be excised en bloc.

PMID- 9152139
TI  - Bilateral Candida parapsilosis endophthalmitis.
AB  - We describe a patient with bilateral, delayed endophthalmitis who underwent
      bilateral pars plana vitrectomy, total capsulectomy, intraocular lens exchange,
      intravitreal injection of amphotericin B, and oral fluconazole therapy. The long
      term inflammation resolved, and vitreous cultures from both eyes yielded Candida
      parapsilosis. Histopathologic examination revealed sequestered yeast forms in the
      capsular bags.

PMID- 9152140
TI  - Dissection along the optic nerve axis by a BB.
AB  - A 13-year-old Hispanic boy suffered a perforating injury to his right eye from a
      BB. The clinical examination and computed tomographic scan revealed questionable
      light perception and a dense foreign body, consistent with a BB, situated behind
      the globe. A vitrectomy was performed that was unsuccessful. Six months later the
      eye was enucleated, and the BB was found to be within the optic nerve sheath.
      Foreign bodies within the optic nerve are uncommon. The foreign body in this
      case, a BB, entered the optic nerve through the nerve head after traversing the
      globe. The histopathologic findings in this unusual case are presented herein.

PMID- 9152141
TI  - Ocular manifestations of disseminated intravascular coagulation in a patient with
      the acquired immunodeficiency syndrome.

PMID- 9152142
TI  - Orbital cellulitis in the acquired immunodeficiency syndrome.

PMID- 9152143
TI  - Bilateral spontaneous subperiosteal hematoma of the orbits: a case report.

PMID- 9152145
TI  - Diffuse iris melanoma in a young patient.

PMID- 9152144
TI  - Lymphocytic choriomeningitis virus: a new addition to the TORCH evaluation.

PMID- 9152146
TI  - Bilateral multifocal choroiditis in Reiter syndrome.

PMID- 9152147
TI  - Corneal sensitivity debate.

PMID- 9152148
TI  - Unperceived visual field defects.

PMID- 9152149
TI  - Optic nerve injury after retrobulbar anesthesia.

PMID- 9152150
TI  - Frequency and clinico-pathological associations of ras mutations in colorectal
      cancer in the Victorian population.
AB  - BACKGROUND: Mutations in the oncogene ras occur in 20-50% of colorectal cancers.
      The presence of these mutations allows screening tests to be developed based on
      the identification of mutant DNA in cells derived from cancers. A study of the
      prevalence and clinicopathological associations of ras mutations was undertaken.
      METHODS: The frequency of mutations in codons 12 and 13 of the K-ras gene was
      investigated in 103 colorectal carcinomas using restriction fragment length
      polymorphism. RESULTS: Mutations were detected in 32% (33/103) of the tumours,
      predominantly in codon 12 (25/33). No mutations were detected in normal-appearing
      mucosa from the same patients. CONCLUSIONS: Analysis of the frequency of ras
      mutations compared with various independent clinical variables revealed a sex
      linked relationship between the presence of a ras mutation and nodal status but
      no correlation with any other clinical parameter was found. The findings suggest
      that screening tests based on ras mutation detection may lack sensitivity because
      of the presence of mutations in only 32% of tumours.

PMID- 9152151
TI  - K-ras mutation and loss of heterozygosity of chromosome 17p and survival in
      colorectal cancer.
AB  - BACKGROUND: The development of colorectal cancer (CRC) is thought to be a
      multistage process involving alterations to several types of genes, including
      oncogenes and tumour suppressor genes. This study examined the associations
      between allelic deletions of chromosome 17p in the region of the p53 gene and K
      ras gene mutation and survival among CRC patients. METHODS: Resected specimens
      from 233 patients were examined. Point mutation of codon 12 of K-ras was assessed
      using a modified polymerase chain reaction method. Allelic deletion of 17p was
      demonstrated by loss of heterozygosity (LOH) with the marker Mfd144. RESULTS:
      Fifty-seven tumours (24%) showed somatic point mutation of codon 12 of K-ras and
      86 tumours (37%) showed LOH of Mfd144. There were 107 tumours (46%) with either K
      ras mutation or LOH and 18 tumours (8%) with both. Compared with patients with
      neither alteration, significantly poorer survival was experienced only by those
      with both alterations (P = 0.015). However, when this variable was introduced
      into a multivariate analysis controlling for the patient's age and tumour stage,
      it failed to show a statistically significant independent effect on survival.
      CONCLUSIONS: Point mutation of K-ras and LOH of Mfd144 in CRC does not add to the
      prognostic information already available from clinicopathological staging.

PMID- 9152152
TI  - Hydrogen sulphide produces diminished fatty acid oxidation in the rat colon in
      vivo: implications for ulcerative colitis.
AB  - BACKGROUND: Several lines of evidence suggest a possible role for reduced forms
      of sulphur (including sulphide) in ulcerative colitis. The aims of this study
      were to assess the metabolic profile of colonic epithelial cells after treatment
      in vivo with hydrogen sulphide and correlate this with mucosal histological
      appearances. METHODS: Adult Sprague-Dawley rats had antegrade Roux-en-Y
      colostomies fashioned to allow access to the 'in-flow' bowel. Animals were
      treated with 2 mL sodium hydrosulphide (10, 20, 30 mmol/L) or saline control
      twice daily via the stoma for four (acute experiments) and 90 (chronic
      experiments) days. Isolated colonic epithelial cell suspensions prepared from
      such animals were incubated in the presence of [1-14C]-labelled n-butyrate (5
      mmol/L) or [6-14C]glucose (5 mmol/L). Metabolic performance was measured
      radiometrically (14CO2 production) and enzymatically (ketone body production and
      lactogenesis). The histological appearances of treated mucosa were scored for
      acute inflammatory changes. RESULTS: There was a highly significant reduction in
      14CO2 production from both n-butyrate and glucose in all groups compared to the
      control in both acute and chronic experiments. There was no difference between
      groups with respect to histological appearance and no evidence of acute
      inflammation in any specimen. CONCLUSIONS: Sodium hydrosulphide impairs rat
      colonic epithelial metabolic performance in vivo, but does not produce mucosal
      inflammation.

PMID- 9152153
TI  - Breast cancer in Western Australia in 1989. V: Outcome at 5 years after
      diagnosis.
AB  - BACKGROUND: A follow-up study was undertaken of all Western Australian women who
      had a new diagnosis of breast cancer during 1989. The aims were to determine
      survival, frequency of recurrence and quality of life (QoL) of Western Australian
      women 5 years after a diagnosis of breast cancer; to determine reasons for choice
      or rejection of reconstructive surgery in those women treated by mastectomy, and
      to determine if the choice of lumpectomy or mastectomy affects subsequent QoL.
      METHODS: The vital status as at 1st June 1994 of all 692 women who had a new
      diagnosis of breast cancer in 1989 was ascertained by electronic linkage to
      official mortality registrations. A subsample of 215 survivors who had originally
      been treated by the nine surgeons who had managed 20 or more cases each was sent
      a reply-paid postal questionnaire asking about follow-up treatment since
      diagnosis, recurrence of disease, current QoL and attitudes to, and use of,
      reconstructive surgery. RESULTS: The overall survival rate at 5 years was 80.8%
      (85.9% and 78.8% for Stage I and II, respectively). Cumulative mortality was 35%
      lower among the third of patients treated by the nine most active surgeons (14%
      vs 22%, P < 0.02), but this may be subject to referral bias. The subsample was
      representative of all surviving cases except for being an average of 2.7 years
      younger at diagnosis (mean ages 55.2 and 57.9 years). The response rate of the
      subsample to the postal questionnaire was 78%. Of women who had had a mastectomy,
      40% had considered having a reconstruction, but only nine (11%) had undergone
      this operation. Median QoL on the Rosser scale (maximum = 1.0) was 0.9. QoL was
      worse for the 23% of patients with a recurrence of breast cancer. Patients
      treated by breast-conserving surgery showed a trend toward a better QoL compared
      with those treated by mastectomy. CONCLUSION: At 5 years after the diagnosis of
      breast cancer, one in five women had died and an estimated one in four of the
      survivors had recurrent disease. Quality of life in the remaining patients, half
      of whom had undergone adjuvant treatment, was very good. These are important
      baseline data against which to judge the impact of mammographic screening.

PMID- 9152155
TI  - Outcome for patients with abdominal aortic aneurysms that are treated non
      surgically.
AB  - BACKGROUND: There are few reports in the literature describing the outcome for
      patients with abdominal aortic aneurysm who are not treated by surgical repair.
      This is in spite of the fact that this group of patients often defines the
      success of surgical treatment. The purpose of this report is to review those
      patients from St George Hospital Kogarah who have been rejected for surgical
      therapy and to examine the long-term outcome and mode of demise of these
      patients. METHODS: At the end of December 1992 we completed a computerized list
      of all patients seen at St George Hospital Kogarah with abdominal aortic
      aneurysm. Since that time we have continued to accrue patients to this list and
      obtain follow-ups prospectively. End points examined in this study were aortic
      aneurysm transverse diameter, sex, age, intercurrent illnesses, reasons for not
      undertaking surgical treatment, length of survival and cause of death. RESULTS:
      The mean age of patients in this series was 77 +/- 8.29 years (SD). Survival at
      yearly intervals for 5 years in our 101 patients were 69, 55, 44, 35 and 33%,
      respectively. For patients with an abdominal aortic aneurysm of < or = 5 cm, the
      5-year survival rate was 42% while for patients with an abdominal aortic aneurysm
      of > 5 cm, the 5-year survival rate was 25%. There were 66 deaths in this series;
      40% were due to cardiopulmonary events and 30% were due to ruptured abdominal
      aortic aneurysm. The median time between presentation and death was 12 months.
      CONCLUSION: The patients from this report were significantly older than those
      reported from previous series. We believe that it will become increasingly
      important to develop methods of selection of patients for current and newer
      modalities of treatment for abdominal aortic aneurysm. It will be increasingly
      important for groups offering these treatments to be able to explain to patients
      what their prognosis is likely to be should they not be selected for those
      treatments.

PMID- 9152154
TI  - Is parathyroid hormone-related protein a sensitive serum marker in advanced
      breast cancer?
AB  - BACKGROUND: To compare already used serum markers in advanced breast cancer,
      namely erythrocyte sedimentation rate (ESR), carcino-embryonic antigen (CEA), and
      polymorphic epithelial mucins (e.g. CA15-3) with a newer potential marker:
      parathyroid hormone related protein (PTHrP). METHODS: A study group of 33
      patients of proven advanced breast cancer was compared with 11 patients with
      benign breast lumps who were undergoing surgery, and eight patients with humoral
      hypercalcaemia of malignancy of non-breast origin. ESR, CA15-3, CEA, PTHrP,
      parathormone (PTH), liver and renal function were measured using commercially
      available kits. Using given reference ranges, results were classified into normal
      versus abnormal, and univariate statistical comparisons were made using Fisher's
      exact test. For multivariate analysis, absolute serum levels were used, and
      multivariate logistic regression models were employed. RESULTS: By univariate
      analysis, only CA15-3 (P = 0.007), and CEA (P = 0.004), were significant markers
      of metastatic disease. By multivariate analysis the only independently
      significant serum marker was CA15-3 (P = 0.043). PTHrP was neither a sensitive
      (22%) nor specific (90.1%) serum marker when compared to CEA or CA15-3. ESR was
      the most sensitive single serum marker (93%). An incidental finding of elevations
      of serum parathormone was found in as many patients as in the study group as
      there were elevations of PTHrP. CONCLUSIONS: PTHrP would not have revealed any
      patients with metastatic disease that would not have been predicted by any
      existing tumour markers including CA15-3, CEA and ESR. The finding of elevated
      PTH in as many patients as PTHrP indicates the possible need for a study
      inclusive of other polypeptide hormones as markers in advanced breast cancer.

PMID- 9152156
TI  - Buerger's disease in Hong Kong: a review of 89 cases.
AB  - BACKGROUND: A retrospective analysis of 103 case records from 1978 to 1996 with a
      provisional diagnosis of Buerger's disease was undertaken at the Department of
      Surgery, University of Hong Kong, Queen Mary Hospital. The aim of the study was
      to elucidate the clinical course and evaluate the results of surgical
      intervention of Buerger's disease in Hong Kong Chinese people. METHODS: Fourteen
      patients were subsequently excluded from the study because of inability of fulfil
      our diagnostic criteria. Data on clinical presentation, investigations,
      indications and results of surgical intervention were reviewed. Sympathectomies
      and arterial reconstructions were performed on 42 and four patients,
      respectively, for critical ischaemia or rest pain. Outcome was analysed with
      respect to the rate of ulcer healing, pattern of recurrence and limb loss.
      RESULTS: The patients were all young male heavy smokers with a mean age of 36.5
      years. The majority of patients (80%) presented with ischaemic ulceration or
      gangrene. Vascular reconstruction was undertaken in four patients and
      satisfactory long-term results were obtained in three patients. Sympathectomy was
      able to relieve symptoms in 87% of operated patients and ischaemic ulceration
      healed in 2.6 (mean) +/- 1.7 (SD) months after the operation. If the patient
      continued to smoke, surgical intervention did not exempt the patient from a
      relapse or amputation. CONCLUSION: Sympathectomy provides short-term pain relief
      and promotes ulcer healing in patients with Buerger's disease but carries no long
      term benefit. Complete abstinence from smoking is the only means of arresting the
      progression of the disease.

PMID- 9152157
TI  - Arterial reconstruction for lower limb ischaemia in Hong Kong Chinese.
AB  - BACKGROUND: Lower limb ischaemia due to peripheral arterial disease is uncommon
      in Chinese people, and few arterial bypass operations have been performed. The
      management of a consecutive series of patients who were admitted to our
      department with severe lower limb ischaemis between March 1990 and October 1996
      is reported here. METHODS: A total of 91 primary arterial bypass operations were
      performed for 83 patients (eight patients had bilateral, or two procedures). Of
      these, 84 operations were for foot salvage and seven operations were for
      debilitating claudication. There were 80 infra-inguinal bypasses, 10 of which
      required additional femoro-femoral crossover grafts to improve in-flow. The
      remaining 11 bypass procedures were performed for aorto-iliac occlusion, which
      included aortobifemoral bypass (5), axillobifemoral bypass (3) and cross-femoral
      bypass (3) grafts. There were 46 male and 37 female patients, with a median age
      of 70 years (36-94). RESULTS: Six patients died (6.6%) postoperatively, all of
      whom were in the foot salvage group. The overall cumulative foot salvage rate and
      graft patency was 84 and 56%, respectively, at 5 years. CONCLUSIONS: These
      results justified the use of the same aggressive approach that was adopted in
      Western countries for the treatment of peripheral arterial disease, which seemed
      to be an emerging problem in Hong Kong.

PMID- 9152158
TI  - ABO blood group incompatibility in liver transplantation: a single-centre
      experience.
AB  - BACKGROUND: For most organ transplantation (Tx), ABO blood group incompatibility
      (ABOI) is an absolute contraindication because of the high incidence of
      hyperacute rejection (HAR). While HAR occurs in ABOI liver Tx (LTx), it is known
      that some liver grafts can be accepted. METHODS: ABO-incompatible (ABOI) liver
      allografts were used in seven of 355 orthotopic LTx operations performed at our
      institution over a 10-year period. All seven recipients were in fulminant hepatic
      failure (FHF) prior to Tx. RESULTS: Following Tx, all grafts functioned
      immediately. One patient died without recovering consciousness. Six patients
      recovered consciousness following Tx but three patients subsequently required re
      transplantation (with ABO-compatible grafts (ABOC)) because of severe acute
      rejection (2) and chronic rejection (1). Hyper-acute rejection did not occur. All
      six patients are now well, with a mean survival of 61.5 months. When compared to
      36 other FHF patients who received ABOC grafts, graft survivals were 3/7 (43%)
      for ABOI versus 23/36 (64%) for ABOC (P = not significant (NS)). Patient
      survivals were 6/7 (85.7%) for ABOI patients and 23/36 (64%) for ABOC (P = NS).
      The re-transplantation rate was significantly higher in the ABOI group (P =
      0.001). CONCLUSIONS: The results confirm that ABOI liver grafts should be used in
      urgent circumstances when compatible grafts are not available. Some grafts
      function indefinitely, while those that fail may function for sufficient time to
      allow successful retransplantation with ABOC grafts.

PMID- 9152159
TI  - Transplantation of adult and paediatric horseshoe kidneys.
AB  - BACKGROUND: The incidence of horseshoe kidneys is between 1 in 300 and 1 in 1600.
      Horseshoe kidneys may be either transplanted into two recipients after division
      of the kidney, or used for en bloc transplantation into one recipient. METHODS:
      We report two cases of adult-to-child and child-to-adult transplantation of
      horseshoe kidneys. Embryology and associated abnormalities are outlined, and
      previous case reports reviewed. RESULTS: One transplant was successful and one
      transplant failed due to an unrecognized C peptide deficiency. CONCLUSIONS:
      Horseshoe kidneys are acceptable as donor organs in renal transplantation.

PMID- 9152160
TI  - Results of open carpal tunnel release: a comprehensive, retrospective study of
      188 hands.
AB  - BACKGROUND: Many recent reports of the results of decompression of the median
      nerve in the carpal tunnel have concentrated on only one aspect of recovery
      (numbness, grip etc.), and there are no reports of a comprehensive study of
      outcome. The aim of the present study was to review comprehensively the results
      of the direct visualization method of decompression of the carpal tunnel and to
      compare them with the published results of endoscopic release. METHODS: Patients'
      perceptions of the severity of pain, numbness and paraesthesiae due to carpal
      tunnel syndrome (CTS), before and after open carpal tunnel release (CTR) in 188
      hands were reviewed retrospectively at a minimum time of follow-up of 18 months.
      Motor and sensory testing, provocation testing and measurement of scar tenderness
      in 135 hands were performed at a clinical review. RESULTS: Subjective results
      showed that 70% experienced a reduction in the severity of pain after CTR, 78% of
      hands experienced a reduction in the severity of paraesthesiae and 77%
      experienced a reduction in the severity of numbness. A total of 49% had
      improvements in all three symptoms after CTR. At the clinical review, sensory
      testing revealed that 59% of hands had normal or slightly diminished light touch,
      35% had normal static two-point discrimination and 61% had normal dynamic two
      point discrimination. Results for Tinel's test, Phalen's test and pressure
      provocation testing were positive in 10% of hands. There was no scar tenderness
      in 38%, no persisting thenar atrophy in 90%. Normal grip strength was found in
      93% and 91% had normal pinch strength. CONCLUSIONS: It was concluded that open
      carpal tunnel release remains a safe and reliable treatment for carpal tunnel
      syndrome. The very low incidence of serious complications from the open technique
      of CTR, when compared with endoscopic CTR as published by different authors in
      the literature, and the comparable clinical results, appears to make the open
      technique a safer and preferable option. However, a properly controlled trial of
      both techniques is necessary to compare them.

PMID- 9152161
TI  - Adverse impact of pneumoperitoneum on intraperitoneal implantation and growth of
      tumour cell suspension in an experimental model.
AB  - BACKGROUND: An investigation of the effect of laparoscopy and CO2
      pneumoperitoneum on the pattern of tumour implantation and growth in the
      peritoneal cavity was carried out. METHODS: A suspension of viable adenocarcinoma
      cells was introduced into the left upper quadrant of the peritoneal cavity of 36
      syngeneic immune-competent rats at laparotomy, laparoscopy with CO2 insufflation,
      and gasless laparoscopy (12 rats in each group). Six days later the peritoneal
      cavity and surgical wounds were examined for macroscopic evidence of implanted
      tumour. The abdominal cavity was divided into sectors and macroscopic tumour
      implantation was determined for each sector and wound. This was confirmed by
      histological examination. RESULTS: While tumour implantation occurred in the
      vicinity of the tumour suspension introduction site in the laparotomy and gasless
      laparoscopy groups, implantation occurred throughout the peritoneal cavity,
      including areas remote to the introduction site, in the laparoscopy with CO2
      insufflation group. Tumour growth was more likely in the port wounds of rats
      undergoing laparoscopy with insufflation than without. CONCLUSIONS: In this
      model, CO2 insufflation during laparoscopy resulted in widespread tumour
      dissemination and implantation, when compared to laparotomy and gasless
      laparoscopy, supporting the postulate that wound metastasis and tumour spread may
      be more likely following laparoscopic cancer surgery in humans when CO2
      insufflation is used.

PMID- 9152163
TI  - Emphysematous cholecystitis.

PMID- 9152162
TI  - Use of a cotton tape tie in laparoscopic colorectal surgery.
AB  - In this short article we describe the use of a cotton tape tie in laparoscopic
      colorectal surgery. This technique is useful in: (i) retraction and manipulation
      of the bowel; (ii) exteriorization of a bulky specimen; and (iii) occlusion of
      the rectal lumen to permit effective cytocidal rectal lavage.

PMID- 9152164
TI  - Differences in patterns of care of prostate cancer, New South Wales, 1991.

PMID- 9152165
TI  - Capsular chondroid metaplasia following total hip arthroplasty.

PMID- 9152166
TI  - Bilateral plasma cell granuloma (inflammatory pseudotumour) of the breast.
AB  - Plasma cell granuloma of the breast is an extremely rare condition. Only one
      other case has been reported in the literature. We report here the second case of
      plasma cell granuloma of the breast. After the initial excision, the lesion
      recurred in both breasts after 5 months.

PMID- 9152167
TI  - Management of acute vascular graft thrombosis associated with HIT syndrome: a
      case report.

PMID- 9152168
TI  - Dermal hydrofluoric acid burns resulting in death.

PMID- 9152169
TI  - Endocarditis after angiography and angioplasty of a subclavian artery stenosis.
AB  - A case of bacterial endocarditis following percutaneous angiography and
      angioplasty of a subclavian artery stenosis is described. Septic complications
      following angiography and angioplasty, and the role of prophylactic antibiotics
      are discussed.

PMID- 9152170
TI  - The Breast Cancer Detection Demonstration Project 25 years later.
AB  - The Breast Cancer Detection Demonstration Project was initiated 25 years ago to
      demonstrate the feasibility of large-scale screening for breast cancer. A
      retrospective view shows that it has more than fulfilled its mission; among other
      important accomplishments it has significantly advanced both the notion and
      science of population-based breast cancer screening and provided a huge data base
      for epidemiologic research.

PMID- 9152171
TI  - Twenty-year follow-up of the breast cancers diagnosed during the Breast Cancer
      Detection Demonstration Project.
AB  - This study reports on the 20-year follow-up of the women diagnosed with breast
      cancer in the Breast Cancer Detection Demonstration Project (BCDDP) between 1973
      and 1980. This project provided 5 years of screening with physical examination
      and two-view mammography for 280,000 volunteer women across the United States.
      Based on a 96% follow-up from 1993 to 1995 of the 4,051 women with breast cancer
      available for analysis, 2,658 (66%) were alive and 1,393 (34%) were dead. A high
      proportion of the cancers were detected by mammography alone, and 28.6% of all
      the cancers were smaller than 1.0 cm. Survival rates were calculated by life
      table method with deaths from breast cancer as the outcome. The adjusted survival
      rate for the entire group was 80.5%, and the observed survival rate was 61.7%.
      Adjusted and observed survival rates were 97.2% and 78.5%, respectively, for
      women with non-invasive cancers and 78.2% and 59.3%, respectively, for those with
      invasive cancers. Lymph node status and the size of the cancer at diagnosis were
      prognostic indicators of survival in the BCDDP Women with invasive cancers and
      negative lymph nodes had an 85.5% breast cancer survival rate and a 65.6%
      observed survival rate. Adjusted survival rates for women with invasive breast
      cancers were 90.2% for cancers smaller than 1 cm, 80.5%, for cancers 1.0 to 1.9
      cm, 70.5% for cancers 2.0 to 4.9 cm, and 60.6% for cancers larger than 5 cm.
      Women 40 to 49 years of age demonstrated a greater survival with noninvasive or
      invasive cancers smaller than 5.0 cm compared with women 50 to 59 and 60 to 69
      years of age at diagnosis. These results from the BCDDP are discussed in the
      context of the recent decline in breast cancer incidence and mortality in the
      United States.

PMID- 9152172
TI  - American Cancer Society guidelines for the early detection of breast cancer:
      update 1997.
AB  - The American Cancer Society (ACS) convened a workshop in March 1997 to consider
      new scientific findings related to breast cancer screening and to determine
      whether these findings warrant a change in the existing ACS guidelines. The
      meeting was timed so that participants could benefit from new data related to
      screening women aged 40 to 49 years. A recommendation based on the new data and
      subsequently approved by the ACS Board of Directors is reported.

PMID- 9152173
TI  - American Cancer Society guidelines for screening and surveillance for early
      detection of colorectal polyps and cancer: update 1997. American Cancer Society
      Detection and Treatment Advisory Group on Colorectal Cancer.
AB  - In the past, differences in opinion among professional groups about colorectal
      cancer screening have been a barrier to colorectal cancer prevention. It is clear
      that screening for colorectal cancer is currently practiced by fewer than 20% of
      American adults. However, a growing consensus now exists that even though we do
      not yet have trial data to compare precisely the various methods for screening,
      there is now both a compelling case for screening and a reasonable set of methods
      that clinicians and patients can consider. By applying the knowledge we already
      have, it is likely that most of the deaths from colorectal cancer in the United
      States could be prevented.

PMID- 9152174
TI  - Clinical highlights from the National Cancer Data Base: 1997.
AB  - The following highlights summarize the principle findings of the NCDB, which are
      presented in more detail in other reports, some of which have been published and
      others of which are in press or submitted awaiting review. Collectively, these
      findings present a broad pattern of NCDB assessment of cancer patterns of care.
      In addition to the resulting journal publications, 1,600 NCDB participating
      hospitals receive a customized summary of similar patterns of care and outcome at
      their facility compared with national norms, which is then used for quality
      assurance purposes.

PMID- 9152175
TI  - Stereotactic core-needle biopsy of the breast: a report of the Joint Task Force
      of the American College of Radiology, American College of Surgeons, and College
      of American Pathologists.
AB  - A national task force consisting of members from the American College of
      Radiology, the American College of Surgeons, and the College of American
      Pathologists examined the issues surrounding stereotactic core-needle biopsy for
      occult breast lesions. Their report includes indications and contraindications,
      informed consent, specimen handling, and management of indeterminate, atypical,
      or discordant lesions.

PMID- 9152176
TI  - Preliminary results of preoperative 5-fluorouracil, low-dose leucovorin, and
      concurrent radiation therapy for clinically resectable T3 rectal cancer.
AB  - PURPOSE: We report the downstaging, sphincter preservation, acute toxicity, and
      preliminary local control and survival results of preoperative 5-fluorouracil (5
      FU), low-dose leucovorin (LV), and concurrent radiation therapy followed by
      postoperative LV/5-FU for treatment of patients with clinically resectable T3
      rectal cancer. MATERIALS AND METHODS: A total of 32 patients received two monthly
      cycles of preoperative LV/5-FU (bolus daily X 5). Radiation therapy (5,040 cGy)
      began concurrently on day 1. Postoperatively, patients received a median of two
      monthly cycles of LV/5-FU (range, 0-10). RESULTS: The complete response rate was
      9 percent pathologic and 13 percent clinical, for a total of 22 percent. Total
      Grade 3+ acute toxicity during the preoperative combined modality segment was 25
      percent (8/32). Of the 20 patients who were thought to initially require an
      abdominoperineal resection and for whom the intent of treatment was sphincter
      preservation, 17 (85 percent) were able to undergo sphincter-preserving surgery.
      With a median follow-up of 22 (3-59) months, none have developed local failure,
      and the three-year actuarial disease-free survival rate was 60 percent.
      CONCLUSION: Our data reveal encouraging downstaging, sphincter preservation and
      acute toxicity with this regimen. Additional follow-up is needed to assess the
      long-term local control and survival rates.

PMID- 9152178
TI  - Abdominoperineal resection and perineal colostomy for low rectal cancer. The
      Lazaro da Silva technique.
AB  - PURPOSE: We sought to evaluate a new technique for creation of a continent
      perineal colostomy following abdominoperineal resection (APR) of the rectum for
      low rectal cancer. METHODS: Nine selected patients with low rectal cancer (two
      males; median age, 55.6 years; classified as Dukes A, 6 patients and as Dukes B,
      3 patients) underwent APR. Following this, the original Lazaro da Silva technique
      was used as follows: 1) for performance of three circular myotomies in the distal
      sigmoid with a distance between each couple of no more than 8 cm; 2) repair of
      the myotomies, thus creating three circular colonic valves, the most distal of
      which remained extraperitoneally; 3) for construction of a perineal colostomy
      lying flush with the perineal skin; 4) after the patient starts consuming a
      regular diet, enemas through the perineal stoma are done, usually twice per week,
      to achieve defecation. Functional outcome was assessed by evaluation of bowel
      movements and neoanal continence. RESULTS: There were no deaths. From January
      1994 until October 1995, no tumor recurrence has occurred, and fecal continence
      has been good. Four of the patients were able to defecate without enemas (2-4
      times per week), and in five patients the self-administration of enemas (2-4
      times a week) were necessary to accomplish defecation. CONCLUSION: Initial
      results with the Lazaro da Silva technique have been encouraging.

PMID- 9152177
TI  - Survival of colorectal carcinoma in the elderly. A prospective study of
      colorectal carcinoma and a five-year follow-up.
AB  - PURPOSE: Colorectal carcinoma in elderly patients has become a more common
      problem in the last decade. There are some physicians who tend to offer a less
      definitive treatment for these patients because of their chronologic age. The
      purpose of this study was to evaluate the long-term survival of elderly patients
      (> 70) who underwent surgery for colorectal carcinoma in comparison with a
      younger group of patients with the same disease. METHODS: Long-term survival of
      patients with colorectal carcinoma who underwent surgery was prospectively
      evaluated. Long-term survival was compared between an elderly group of patients
      (age, > 70) and a younger group of patients. RESULTS: There was no significant
      difference in the five-year survival between the two age groups. Patients'
      survival was influenced by stage of the disease and type of operation (emergency
      vs. elective). CONCLUSIONS: Treatment decisions in elderly patients with
      colorectal carcinoma should not be influenced by the chronologic age of the
      patient.

PMID- 9152179
TI  - Flat cancers do develop in the polyp-free large intestine.
AB  - PURPOSE AND BACKGROUND: Qualitative and quantitative analysis of many flat early
      cancers that have been discovered during the last decade led us to recognize that
      a flat route of cancer development de novo is as important a route as the
      polypoid one. We aim to prove through a longitudinal study that these flat early
      cancers indeed develop in flat mucosa and not in an adenomatous polyp. METHODS:
      From January 1, 1990, to July 31, 1994, 554 patients underwent at least two
      colonoscopies. These patients consisted of 364 males, and average age was 59
      years. We searched for flat early cancers developing in polyp-free colorectal
      mucosa on or after a second colonoscopy. Polyp-free mucosa here means an
      intestinal segment proved to possess no adenomatous polyp during the preceding
      colonoscopies, irrespective of the presence of polyps elsewhere. RESULTS: Four
      flat early cancers were found developing in polyp-free colonic mucosa in four
      patients. Average age of the patients was 67 years. Locations of the cancers were
      the transverse (3) and descending colons (1). The shapes were all depressed, and
      average size of the lesions was 11 mm. Two lesions were endoscopically resected,
      and two by surgery. CONCLUSION: These four depressed cancers developing in polyp
      free mucosa show that flat early colorectal cancers do arise de novo and not from
      an adenomatous polyp having collapsed on itself.

PMID- 9152180
TI  - What happens to a pelvic pouch when a fistula develops?
AB  - PURPOSE: The aim of this article is to determine the outcome of the pelvic pouch
      after the occurrence of a fistula. MATERIALS AND METHODS: From 1983 to 1995,
      1,040 pelvic pouch surgeries were done at our institution. We reviewed the
      records of all patients with pouch-related fistulas. Data were collected from
      chart reviews and our pouch registry. RESULTS: Among 59 patients (22 males) with
      fistulas, mean age was 33 (range, 19-57) years. Preoperative diagnosis was
      mucosal ulcerative colitis (n = 52), indeterminate colitis (n = 6), and familial
      polyposis (n = 1). Site of fistulas included pouch/vaginal (n = 24), pouch/
      cutaneous (n = 11), pouch/perineal (n = 16), and pouch/ presacral (n = 8).
      Postoperative diagnosis was mucosal ulcerative colitis (n = 40), Crohn's disease
      (n = 14), indeterminate colitis (n = 4), and familial polyposis (n = 1). One
      hundred eleven (range, 1-7) surgeries for treatment were performed. At a mean
      follow-up of 26 (range, 1-121) months, 19 pouches (32 percent) had been excised,
      34 patients had functioning pouches and no fistula, 5 patients had a closed
      fistula but refused ileostomy closure, and 1-patient had died of unrelated causes
      (but the fistula was closed). Pouch type and preoperative diagnosis did not
      statistically affect pouch failure rates (P = 0.43 and 0.10. respectively).
      CONCLUSION: Successful treatment of fistula from a pelvic pouch can be achieved
      in more than 60 percent of patients. However, multiple procedures may be needed
      for a successful outcome. Ultimately, 32 percent had their pouches excised.

PMID- 9152181
TI  - Pouch salvage. Long-term outcome.
AB  - PURPOSE: The aim of this study was to determine the outcome of pouch salvage
      operations and the factors that may influence successful reconstructions.
      METHODS: This retrospective review includes data from 198 patients who had
      undergone restorative proctocolectomy at a single institution during an 11-year
      period. All patients who had undergone attempted pouch salvage and who still had
      a pouch in situ were reviewed by both postal questionnaire and at interview in
      the outpatients clinic. RESULTS: Of 198 patients who underwent restorative
      proctocolectomy and ileal pouch-anal anastomosis, 27 (13.6 percent) presented
      with pouch-specific complications requiring pouch salvage. A further five
      patients requiring pouch salvage were referred from other centers. Of 32 patients
      who underwent attempted pouch salvage, 16 (50 percent) had a successful outcome,
      12 (37.5 percent) had pouch excision, and 3 (9 percent) are still defunctioned.
      There was one death (3 percent) in this series. Pelvic sepsis was a major cause
      of pouch failure, being present in 50 percent (8/16) of failed salvage
      procedures, and accounting for 58 percent (7/12) of pouch excisions. CONCLUSIONS:
      Salvage surgery for major complications following ileoanal pouch construction is
      worthwhile in the absence of major pelvic sepsis. Overall success rate is 50
      percent, and these results may be acceptable to highly motivated patients.

PMID- 9152182
TI  - Preliminary report on the Mount Sinai Hospital Inflammatory Bowel Disease
      Genetics Project.
AB  - BACKGROUND: Although the etiology of inflammatory bowel disease (IBD) is unknown,
      there is increasing evidence that genetic predisposition plays a major etiologic
      role. To provide the framework for gene identification using a positional cloning
      approach, ascertainment of families with multiple affected members and careful
      documentation of pedigrees are essential. OBJECTIVE: To report the initial
      findings of the IBD Genetics Project of the Mount Sinai Hospital IBD Research
      Unit. METHODS: All records of patients with ulcerative colitis and Crohn's
      disease followed at the Mount Sinai Hospital IBD Unit were reviewed. A
      questionnaire was sent to all patients to ascertain those with a family history
      of IBD. Patients with a presumed family history were contacted by a research
      assistant, and after confirmation of diagnosis, relevant clinical information,
      pedigrees, and consent to contact family members were obtained. Blood for DNA and
      cell line preparation were collected from affected and nonaffected family
      members. RESULTS: Of 2,504 patients registered in the IBD database, 231 (9.2
      percent) were found to have an affected family member: 96 of 964 (10 percent)
      with Crohn's disease (CD) and 135 of 1,540 (8.8 percent) with ulcerative colitis
      (UC). A mean of 2.4 family members were affected. In families in which the
      proband had CD, 82.3 percent had only two affected family members, 78.1 percent
      had only family members affected with CD, and 82.3 percent had only first-degree
      family members affected. In families in which the proband had UC, 70.4 percent
      had only two affected family members, 71.1 percent had only family members
      affected with UC, and 65.2 percent had only first-degree family members affected.
      In the 231 families, there were 103 sibling pairs: 46 percent with CD, 28 percent
      with UC, and 26 percent with CD/UC. CONCLUSION: These data suggest that
      approximately 10 percent of IBD patients have affected family members, with the
      rate being similar in UC and CD. Future research is directed to genome scanning
      and linkage analysis in this cohort of patients.

PMID- 9152183
TI  - Surgical management of ileosigmoid fistulas in Crohn's disease.
AB  - Ileosigmoid fistulas are found in Crohn's disease and may present a surgical
      dilemma. PURPOSE: This study was designed to examine surgical practice to
      determine types of intervention, enumerate complications, and elicit guidelines
      for surgical management. METHOD: The medical records of patients with ileosigmoid
      fistula and Crohn's disease from 1975 to 1995 were reviewed. RESULTS: Ninety
      patients (44 men) were studied. A preoperative diagnosis of ileosigmoid fistula
      was made in 77 percent of patients. Sigmoid repair was performed in 43 patients
      (47.8 percent), sigmoid resection in 32 patients (35.6 percent), 12 patients
      (13.3 percent) underwent more extensive procedures, and 3 patients (3.3 percent)
      either had surgery elsewhere or were observed. The fistula was never directly
      responsible for a stoma. The repair and resection groups were similar with
      respect to age, length of Crohn's disease, and preoperative symptoms. There was
      no significant difference between groups in the incidence of postoperative
      complications; there were no postoperative deaths. Average length of stay was 8.3
      days following repair and 9.9 days after resection. Reasons for resection
      included significant purulence or inflammation, a large fistula defect, a defect
      on the mesenteric border of the sigmoid, and active sigmoid Crohn's disease.
      Surgeon's assessment of the presence of Crohn's disease in the sigmoid correlated
      with pathologic examination and was aided by knowledge of recent endoscopic
      appearance and biopsy results; intraoperative frozen section and colonoscopy were
      helpful in distinguishing serosal inflammation from active Crohn's disease.
      CONCLUSION: Contrast studies identified 77 percent of ileosigmoid fistulas
      preoperatively. Performing repair rather than resection does not increase the
      risk of complications, if standard surgical principles are followed. Preoperative
      or intraoperative endoscopy assists the surgical evaluation of the sigmoid.

PMID- 9152184
TI  - Restorative proctocolectomy in patients older than fifty years.
AB  - PURPOSE: This study was undertaken to compare functional results, complications,
      preoperative durations of disease, and rates of dysplasia and neoplasia between
      older and younger chronic ulcerative colitis patients undergoing restorative
      proctocolectomy (RPC) with mucosectomy. METHODS: A total of 392 patients with a
      preoperative diagnosis of chronic ulcerative colitis underwent elective RPC with
      mucosection and handsewn ileoanal anastomosis. Pathologic reports were reviewed,
      with specific reference to findings of dysplasia or cancer. Functional results
      concerning the number of bowel movements per 24 hour period and the incidence of
      fecal soilage were obtained by direct or telephone patient interview. FINDINGS:
      Group I consisted of 326 patients aged 5 to 49 (mean, 30.9) years and 160 women.
      Group II comprised 66 patients aged 50 to 74 (mean, 56.9) years and 29 women.
      Duration of disease was significantly longer in the older group (6.2 vs. 15.6
      years; P < 0.001). The older group had significantly higher rates of dysplasia
      (29/326 vs. 19/66; P < 0.0001) and malignancy (14/326 vs. 9/66; P = 0.003). Rates
      of complication, hospital days following RPC, and total hospital days for all
      causes were comparable between groups. Perfect day-time continence was observed
      in 81.6 percent of Group I and 80 percent of Group II patients (213/261 vs.
      40/50; P = 0.79). Perfect continence during sleep was observed in 65.1 percent of
      Group I and 62 percent of Group II patients (170/261 vs. 31/50; P = 0.67). Mean
      number of bowel movements per 24 hour period for Group I was 6.3 +/- 0.2 and for
      Group II was 7.4 +/- 0.5. Mean difference, one movement per 24 hours, was not
      significant (95 percent confidence interval, -0.02 to 2.1; t = 1.95, P = 0.055).
      CONCLUSIONS: We conclude that patients older than 50 years are suitable
      candidates for RPC with mucosectomy. Functional results and complication rates
      are similar to those observed among younger patients. Patients older than 50
      years have a significantly higher rate of concurrent dysplasia and malignant
      degeneration than younger patients, most probably because of a longer duration of
      disease. RPC with mucosal excision potentially lowers this risk by elimination of
      all colorectal mucosa.

PMID- 9152185
TI  - Afferent limb obstruction complicating ileal pouch-anal anastomosis.
AB  - PURPOSE: Small-bowel obstruction is a common complication after ileal pouch-anal
      anastomosis (IPAA). Acute angulation of the afferent limb at the pouch inlet is
      the cause of obstruction in a subset of patients requiring laparotomy. METHODS:
      Patients were identified from the Lahey Clinic ileoanal pouch registry, a
      prospective computerized database of all patients who have undergone IPAA since
      1980. Records of patients who were identified as having afferent limb obstruction
      as a cause of bowel obstruction after IPAA were reviewed. RESULTS: A total of 567
      patients had undergone total proctocolectomy and ileoanal J-pouch at time of the
      study. Of 122 patients with one or more episodes of obstruction after IPAA, 48
      required operative intervention. Afferent limb obstruction was identified as the
      cause of obstruction in six patients (12 percent). The most common presentation
      was recurrent partial obstruction (4 of 6 patients). Contrast small-bowel series
      and enemas were suggestive of obstruction in four of six patients, the most
      consistent radiographic finding being small-bowel dilation to the level of the
      pouch inlet. All patients underwent laparotomy for unresolved obstruction.
      Intraoperatively, the afferent limb was found to be adherent posterior to the
      pouch, causing acute angulation at the pouch inlet. Rather than risk injury to
      the pouch or its mesentery, the obstruction was bypassed by side-to-side
      anastomosis of the afferent limb to the pouch (enteroenterostomy) in five of six
      patients. One patient underwent ileostomy only because of technical
      considerations. Two patients required re-exploration and pexy of the afferent
      limb to the pelvic sidewall (pouchopexy) to relieve recurrent afferent limb
      obstruction. CONCLUSION: Afferent limb obstruction should be suspected in
      patients with recurrent obstruction after IPAA. Bypass of the obstructed segment
      from distal ileum to the pouch is safe and effective treatment. Because of the
      risk of recurrent afferent limb angulation, concurrent pouchopexy should be
      considered.

PMID- 9152187
TI  - Prediction of incontinence following low anterior resection for rectal carcinoma.
AB  - PURPOSE: This study was performed to predict incontinence following low anterior
      resection for rectal cancer. METHODS: Preoperatively, 21 patients were evaluated
      via patient history and a physical examination that included anal manometric
      studies. Six months postoperatively, repeat manometric studies and clinical
      evaluations were performed to assess the level of continence. Degree of
      continence was graded based on severity of the dysfunction and grade of the
      continence score. RESULTS: The formula used for predicted postoperative resting
      pressure is as follows: predicted postoperative resting pressure = 0.42 x
      preoperative resting pressure +1.56 x length of remaining rectum +12.37 (R2 =
      0.58; P < 0.001). It was demonstrated that patients with low predicted
      postoperative resting pressures (< 30 mmHg) had incontinence, and those with high
      predicted postoperative resting pressures (> 35 mmHg) were continent. There were
      significant correlations between length of the remaining rectum and ratio of the
      decrease in maximum resting pressure (postoperative/preoperative maximum resting
      pressure; r = 0.63; P < 0.01). CONCLUSIONS: Continence following low anterior
      resection may be influenced by maximum resting pressure function of the internal
      anal sphincter; if it is injured during surgery, incontinence will occur. We may
      be able to foretell incontinence by using the predicted postoperative resting
      pressure formula, which is calculated by using preoperative resting pressure
      measurements and then determining the length of the remaining rectum.

PMID- 9152186
TI  - Acute colonic diverticulitis in the young.
AB  - BACKGROUND: Colonic diverticulitis in the young has been considered to have a
      virulent course, high morbidity, and high operative rate. As a result, elective
      resection of the involved colonic segment after the first clinical episode has
      been the usual practice. PURPOSE: This study presents our experience with acute
      diverticulitis in the young. METHODS: In the last nine years, 63 patients younger
      than 45 years were treated for acute diverticulitis at our institution. A
      retrospective review was performed to determine the clinical course and outcome
      of these patients. RESULTS: Clinical presentations, radiographic tests, operative
      findings, and pathology results revealed that 57 patients had a pericolonic
      contained disease (Hinchey State I). Two patients had a large pelvic abscess
      (Hinchey Stage II), and four patients had a diffuse peritonitis (Hinchey Stage
      III). Forty-one patients (65 percent) were successfully treated medically with
      antibiotics and bowel rest. Of 22 patients (35 percent) who underwent emergent
      operations, 12 patients' diseases had been erroneously diagnosed preoperatively
      (9 "appendicitis"). CONCLUSION: Diverticulitis at a young age does not have a
      specific aggressive nature. Although, it is associated with a high rate of
      emergency operations, many of these are performed for a mistaken diagnosis. The
      recommendation for routine elective resection following the first episode of
      diverticulitis should be reassessed.

PMID- 9152188
TI  - Viscous fluid expulsion in the evaluation of the constipated patient.
AB  - PURPOSE: The aim of this study was to evaluate a viscous fluid expulsion test as
      a method for quantifying rectal outlet obstruction. METHODS: We examined the
      ability of 30 severely constipated patients and 40 healthy control subjects to
      expel a viscous fluid simulating feces. RESULTS: Constipated patients with
      defecographic rectal retention expelled a significant lower viscous fluid volume
      compared with controls (P < 0.0001). Considering the viscous fluid expulsion test
      to be positive if the patient expelled less than 160 ml of fluid (lower 95
      percent confidence value in healthy controls) and using the presence of
      defecographic rectal outlet obstruction as a reference, the predictive value of a
      negative viscous fluid expulsion test was 100 percent, the predictive value of a
      positive test was 67 percent, and sensitivity and specificity was 100 percent and
      82 percent, respectively. The viscous fluid test identified symptomatic outlet
      obstruction in almost twice as many patients as did defecography. Some patients,
      however are-despite their obstructive symptoms-able to evacuate their rectum when
      examined in the laboratory. CONCLUSION: The viscous fluid expulsion test is a
      simple, reproducible, nonionizing, and low-cost method of quantifying rectal
      outlet obstruction. A positive test result should lead to a defecography, whereas
      a negative test result renders defecography dispensable and spares the patient
      from pelvic radiation.

PMID- 9152189
TI  - Mechanical bowel preparation for elective colorectal surgery. A prospective,
      randomized, surgeon-blinded trial comparing sodium phosphate and polyethylene
      glycol-based oral lavage solutions.
AB  - AIM: The aim of this study was to compare the cleansing ability, patient
      compliance, and safety of two oral solutions for elective colorectal surgery.
      METHODS: All eligible patients were prospectively randomized to receive either 4
      l of standard polyethylene glycol (PEG) solution or 90 ml of sodium phosphate
      (NaP) as mechanical bowel preparation for colorectal surgery. A detailed
      questionnaire was used to assess patient compliance. In addition, the surgeons,
      blinded to the preparation, intraoperatively evaluated its quality. Postoperative
      septic complications were also assessed. The calcium serum level was monitored
      before and after bowel preparation. Statistical analysis was performed using the
      Wilcoxon's rank-sum test and Fisher's exact test. RESULTS: Two hundred patients,
      well matched for age, gender, and diagnosis, were prospectively randomized to
      receive either PEG or NaP solutions for elective colorectal surgery. All patients
      completed all phases of the trial. There was a significant decrease in serum
      calcium levels after administration of both NaP (mean, 9.3-8.8 mg/dl) and PEG
      (9.2-8.9 mg/dl), respectively (P < 0.0001), with no clinical sequelae. However,
      patient tolerance to NaP was superior to PEG: less trouble drinking the
      preparation (17 vs. 32 percent; P < 0.0002), less abdominal pain (12 vs. 22
      percent; P = 0.004), less bloating (7 vs. 28 percent), and less fatigue (8 vs. 17
      percent), respectively. Additionally, 65 percent of patients who received the NaP
      preparation stated they would repeat this preparation again compared with only 25
      percent for the PEG group (P < 0.0001). Ninety-five percent of patients who
      received the NaP solution tolerated 100 percent of the solution compared with
      only 37 percent of the PEG group (P < 0.0001). For quality of cleansing, surgeons
      scored NaP as "excellent" or "good" in 87 compared with 76 percent after PEG (P =
      not significant). Rates of septic and anastomotic complications were 1 percent
      and 1 percent for NaP and 4 percent and 1 percent for PEG, respectively (P = not
      significant). CONCLUSION: Both oral solutions proved to be equally effective and
      safe. However, patient tolerance of the small volume of NaP demonstrated a clear
      advantage over the traditional PEG solution.

PMID- 9152190
TI  - Complications of laparoscopic colorectal surgery. Analysis and comparison of
      early vs. latter experience.
AB  - PURPOSE: The aim of this study was to test if the techniques learned during our
      early learning experience have proved to be effective in reducing the
      complications specifically related to the laparoscopic technique of colorectal
      surgery. METHODS: From October 1991 until July 1996, 195 laparoscopic operations
      were performed on the colon and the rectum. These data were divided into "early"
      and "latter" groups. The conversion reasons and early and late postoperative
      complications were analyzed and compared. RESULTS: Incidence of conversions
      required because of iatrogenic injuries showed a decline from 7.3 percent in the
      early group to 1.4 percent in the latter group. Sixty-six postoperative
      complications were observed in 59 (30.3 percent) patients. Complications
      specifically related to the technique of laparoscopic surgery occurred in nine
      (4.6 percent) patients. These were postoperative bleeding in three patients, port
      site hernias in five patients, and left ureteric stricture in one patient. Eight
      (6.5 percent) of these complications occurred in the early group, whereas one
      (1.4 percent) occurred in the latter group. Analyzing the conversions caused by
      intraoperative iatrogenic injuries and the specific postoperative complications
      together reveals that the incidence of 13.8 percent (17/123) in the early group
      has been reduced significantly to 2.8 percent (2/72) in the latter group.
      CONCLUSIONS: On the basis of our experience, we have identified techniques, which
      are discussed in detail, to make laparoscopic colorectal surgery safe. Strict
      adherence to these techniques has significantly reduced the incidence of
      complications, specifically those related to the laparoscopic technique.

PMID- 9152191
TI  - Lateral internal sphincterotomy for fissure-in-ano--revisited.
AB  - PURPOSE: A disturbing complication rate following lateral internal sphincterotomy
      (LIS) has recently been reported, and this study assessed our complication rate.
      METHODS: Charts of 312 patients who were operated on between January 1975 and
      December 1993 were reviewed. RESULTS: There were 148 men (47.5 percent) and 164
      women (52.5 percent), ranging in age from 16 to 95 (mean, 40) years. Two hundred
      sixty-five patients underwent LIS as a primary and sole procedure. Mean follow-up
      time was 20.4 months (range, 2 weeks-215 months). Healing times were less than
      one month (11.6 percent), one month (73.2 percent), one to two months (9.6
      percent), and more than two months, 5.6 percent. Twenty-three complications (8.7
      percent) occurred in 20 (7.5 percent) of the 265 patients: delayed healing (> 60
      days) of the sphincterotomy site (13); persistence or recurrence of the fissure
      (3); wound infection (2); incontinence to flatus (1); soiling (1); temporary
      incontinence to flatus and stool (1); prolapsed hemorrhoids (1); fecal impaction
      (1). Most complications were minor and resolved spontaneously. Reoperations
      included one revision and one hemorrhoidectomy. CONCLUSIONS: This review supports
      the belief that LIS is a good operation for patients with chronic anal fissure
      and can successfully be performed under local anesthetic as an outpatient
      procedure with an acceptable complication rate.

PMID- 9152192
TI  - Characteristics of metachronous colorectal carcinoma occurring despite
      colonoscopic surveillance.
AB  - PURPOSE: Metachronous colorectal cancer still occurs in a small percentage of
      patients, despite colonoscopic surveillance. Cancers in hereditary nonpolyposis
      colorectal cancer for which there is a high risk of metachronous cancer show
      distinctive DNA changes termed replication errors (RER+). Ten to 20 percent of
      sporadic colorectal cancers are also RER+. The aim of this study was to identify
      factors predictive of metachronous colorectal cancer, despite colonoscopic
      surveillance. Clinicopathologic characteristics and RER status of cancers were
      examined. METHODS: Colorectal cancer patients, who entered into a surveillance
      program of being examined with colonoscopy within six months of surgery and then
      at intervals of three years thereafter, were reviewed. The 433 patients compliant
      with the protocol who had had more than one colonoscopy had been followed up for
      a mean of 3.8 +/- 2.2 years. DNA was extracted from archival paraffin-embedded
      cancer tissue for determination of RER status. RESULTS: Ten cases of metachronous
      cancer were identified, giving a rate of 0.61 percent per year. The site of the
      index cancer in patients who later developed metachronous cancer was
      predominantly proximal (P = 0.0007), and these cancers were more likely to have
      mucinous histology (P < 0.0005). Three of 10 (30 percent) index cancers were
      RER+, which was not significantly different from unselected series of control
      colorectal cancers in which 20 of 108 (18.5 percent) were RER+. DISCUSSION: This
      study documents the rate of metachronous cancer among patients compliant with a
      defined colonoscopic screening program and suggests that the risk is highest in
      patients with a proximal mucinous cancer. RER status does not appear to be a very
      strong predictive factor, and this study does not support its use as a guide to
      the frequency of surveillance colonoscopy. More data would be required to
      determine if RER positivity conferred a relative risk of 3.3 or less.

PMID- 9152193
TI  - Feasibility study for use of brush cytology as a complementary method for
      diagnosis of rectal cancer.
AB  - Brush cytology has previously been described as a feasible method for accurately
      diagnosing colorectal cancer. PURPOSE: This study was designed: 1) to determine
      the sensitivity and specificity of brush cytology for the diagnosis of rectal
      cancer; 2) to prospectively assess the extent of interobserver variability with
      this technique; 3) to prospectively examine the cost impact of the addition of
      brush cytology as a routine method of confirming the diagnosis of rectal cancer.
      PATIENTS AND METHODS: Three hundred fifty-seven patients who attended a rectal
      clinica and who were found to have a lesion between January 1990 and March 1996
      were assessed. Each patient underwent rigid proctoscopy, followed by brush
      cytology and tissue biopsy. Results were compared with the final histologic
      diagnosis in each patient. The brushings from the last 92 consecutive patients in
      this series were independently examined by four cytologists and a pathologist to
      determine the rate of interobserver variability. RESULTS: Rectal adenocarcinoma
      was confirmed from surgically resected specimens in 303 patients. Brush cytology
      accurately diagnosed 278 of them. Of the remaining 25 patients, two had brushings
      that were insufficient for diagnosis. There was one false-positive case. Forceps
      biopsy correctly identified cancer in 260 patients, with no false-positive
      interpretations. Brush cytology accurately identified 53 of 54 adenomas as being
      benign, and forceps biopsy correctly identified all as benign. Sensitivity of
      brush cytology in this series was 92 percent, with a specificity of 92 percent.
      Interobserver agreement was 84 percent. Actual costs incurred with this method
      was an additional $17.00 per patient. CONCLUSIONS: Brush cytology can accurately
      diagnose rectal cancer in a high proportion of patients. Interobserver variation
      is low and compares favorably with other forms of cytologic interpretation. The
      additional cost remains a concern but can be kept within acceptable proportion.

PMID- 9152194
TI  - Endoluminal ultrasound diagnosis and operative management of rectal
      endometriosis.
AB  - PURPOSE: Endorectal ultrasound was performed in patients with endometriosis to
      evaluate the role of this technique for rectal wall involvement and to evaluate
      the position of preoperative diagnosis in the operative management of rectal
      endometriosis. METHODS: Sixteen patients with suspected fixation of endometriomas
      to the rectal wall during bimanual examination were included in the study.
      Endorectal ultrasound was performed using a real time unit with a 7.5 MHz
      endorectal transducer. The probe was introduced via a rectoscope into the rectum
      up to the rectosigmoid. RESULTS: Endometriosis was confirmed histopathologically
      in all patients. In six patients rectal wall involvement was diagnosed, in two
      patients endometriomas were adjacent to the rectal wall, and in eight patients
      rectal wall involvement could be excluded. Preoperative diagnosis was confirmed
      in all patients during operation. Laparotomy was performed in those patients with
      preoperatively diagnosed rectal wall involvement, whereas the remaining patients
      were treated laparoscopically. Endometriomas with rectal wall involvement were
      treated in five of six patients with resection of the affected bowel
      predominantly by low anterior resection. CONCLUSIONS: Preoperative endorectal
      ultrasound is a reliable technique to visualize perirectal endometriomas and to
      assess rectal wall involvement. Based on preoperative endosonographic diagnosis,
      an operative management was established with laparotomy and resection of the
      affected bowel in cases of rectal wall involvement.

PMID- 9152195
TI  - Feasibility of the transparent cap-fitted colonoscope for screening and mucosal
      resection.
AB  - PURPOSE: A transparent plastic cap of 17 mm in outer diameter, 15 mm in inner
      diameter, and 10 mm in length can be easily attached to the tip of a colonoscope.
      By using the cap, a better view of the lesions hiding at the opposite side of the
      fold can be obtained. When a flat colonic lesion is found, a submucosal injection
      of saline solution is performed, the target mucosa is sucked inside the cap,
      snared under a full endoscopic suction, and resected by an electrical current.
      This procedure is called endoscopic mucosal resection using transparent cap
      fitted endoscope (EMRC). Feasibility of the cap-fitted colonoscope for screening
      colonoscopic examination and mucosal resection was evaluated. MATERIALS AND
      METHODS: One hundred forty patients were randomly allocated for screening with a
      normal colonoscope (NCF) or that with the cap-fitted colonoscope (CCF). Average
      time for insertion up to the cecum, patients' discomfort during insertion
      expressed in 4 degrees, and average number of lesions found in one patient were
      compared. Thirty lesions randomly allocated for mucosal resection with
      conventional strip biopsy or EMRC were also evaluated. RESULTS: Time consumed for
      insertion up to the cecum with the CCF (12.4 +/- 6.6 minutes) was the same as
      that with the NCF (12.3 +/- 5.2 minutes), and there was no significant difference
      in patients' discomfort; however, the average number of lesions found in one
      patient was larger when using the CCF (0.86 +/- 0.96) than when using the NCF
      (0.58 +/- 0.81). For mucosal resection, 40 flat or wide-based lesions including 6
      mucosal carcinomas were resected with EMRC. We experienced only one pinhole
      perforation of the ascending colon by heat damage, which was treated successfully
      by surgery. There was no other major complication or recurrence. CONCLUSION: The
      cap-fitted endoscope was equal in maneuverability, was excellent in sensitivity
      in comparison with the regular colonoscope, and was thought to be feasible both
      in screening and mucosal resection.

PMID- 9152196
TI  - Pseudomembranous colitis with associated fulminant ileitis in the
      defunctionalized limb of a jejunal-ileal bypass. Report of a case.
AB  - Presented is what is believed to be the first reported case of a defunctionalized
      limb of small intestine serving as a reservoir for Clostridium difficile. Because
      of the altered intestinal continuity, the ensuing enteritis and colitis failed to
      respond to nonoperative management. Current treatment strategies are reviewed.
      Surgical intervention, including restoration of normal gastrointestinal
      continuity, should be considered early in the hospital course of this patient
      population.

PMID- 9152197
TI  - Restorative proctocolectomy for idiopathic megarectum: postoperative recovery of
      hypotonic anal sphincters. Report of two cases.
AB  - PURPOSE: Restorative proctocolectomy has been advocated in the treatment of
      idiopathic megacolon, provided there is normal sphincter function. We report two
      patients undergoing this procedure, despite abnormal sphincter function. METHODS:
      Anorectal manometry and detailed symptom review were performed both
      preoperatively and at various stages postoperatively in two young patients with
      idiopathic megarectum. RESULTS: Both patients had progressive sphincter recovery
      postoperatively, shown both manometrically and with symptomatic review.
      CONCLUSION: Low preoperative sphincter pressures in young patients with
      idiopathic megarectum may not preclude successful outcome after restorative
      proctocolectomy.

PMID- 9152199
TI  - Submucosal anal injection in the treatment of pelvic malignancies.

PMID- 9152198
TI  - Intracolonic bypass procedure.

PMID- 9152200
TI  - Effects of transcranial electrical and magnetic stimulation on reciprocal
      inhibition in the human arm.
AB  - We studied the effects of transcranial electrical stimulation (TES) and
      transcranial magnetic stimulation (TMS), delivered at intensities below the
      threshold for evoking an electromyographic response, on the disynaptic and
      presynaptic phases of reciprocal inhibition in 8 healthy subjects. After TES, the
      H-reflex evoked in the flexor carpi radialis (FCR) muscle was strongly
      facilitated when the cortical stimulus was given 4.0-4.5 ms after the test
      stimulus (median nerve stimulus). TES reduced the disynaptic phase of reciprocal
      inhibition most strongly when the cortical stimulus followed the test stimulus by
      3.0-3.5 ms. TES also reduced presynaptic inhibition, but with a time course that
      was identical to that of the facilitation of the uninhibited H-reflex. After
      subthreshold TMS, the facilitation of the H-reflex showed at least 2 peaks, one
      occurring when the cortical stimulus was given 2 ms after the test stimulus and
      the other when the cortical stimulus followed the test stimulus by 0.5 to -1.5
      ms. The effects of TMS on the 2 phases of reciprocal inhibition were similar, and
      in both cases the disinhibitory effects had essentially the same time course as
      the facilitatory effect of TMS on the uninhibited H-reflex. The different effects
      of TES on the 2 phases of reciprocal inhibition provide evidence of the
      presynaptic nature of the second phase. The absence of a difference in the effect
      of TMS on the 2 phases could be due to the more temporally dispersed descending
      volley after TMS.

PMID- 9152201
TI  - Responses of human single motor units to transcranial magnetic stimulation.
AB  - Transcranial electromagnetic brain stimuli elicit a complex response in the
      electromyogram of active human hand muscles. Relatively weak stimuli evoke a
      short-latency primary response via a presumably monosynaptic corticospinal path.
      This is followed by a silent period that is terminated by a second peak at a
      latency of 50-80 ms. The responses evoked in single motor units in flexor
      digitorum profundus (FDP) were recorded. Responses were elicited at the second
      peak latency only in trials in which no primary response was elicited in that
      unit, and only when the stimulus was given during the first half of the
      interspike interval (ISI). When given during the second half of the ISI, the same
      stimulus evoked a primary response but no second peak response. Stronger stimuli
      suppressed the second peak by evoking a primary response in more trials. Having
      discharged at about 20 ms latency, the parent motoneurone was unable to discharge
      again at second-peak latency, 30-60 ms later. The response at second-peak latency
      was not modified by disengaging both FDP and the extensors of the distal
      interphalangeal joint. Hence, this response is not secondary to a stretch reflex
      provoked by activation of the finger extensors, nor is it the result of a
      cutaneous signal resulting from movement of the finger. The latencies suggest
      that the corticospinal volley evokes a beta-motoneurone-mediated twitch in FDP
      muscle spindles, which elicits an afferent volley that activates the motoneurone
      reflexly. The first 100 ms or so of the silent period is due to the realignment
      of the first post-stimulus spike in most trials to corticospinal latency; i.e.
      this is not necessarily the result of an inhibitory or disfacilitatory process.
      Still stronger stimuli increase the duration of the ISI in which the stimulus is
      given, indicating the presence of an inhibitory/disfacilitatory process.

PMID- 9152202
TI  - Magnetic stimulation of the lumbosacral vertebral column in children: normal
      values and possible sites of stimulation.
AB  - We describe a technique of lumbosacral magnetic stimulation (MS) using an 8
      shaped coil in 44 normal children and 7 normal adults on the lower limb muscles.
      In most child subjects and some adult subjects, we observed two peaks in
      amplitude of the motor evoked potential (MEP) following MS when the coil was
      moved caudally from Th8 to S2. The rostral peaks of MEP were elicited at L1/2,
      and the caudal peaks were elicited below L3. Rostral peak amplitudes were
      considerably higher in younger children than in adolescents and adults. MEP
      latencies tended to decrease as the coil was moved from Th11 to L4/5, and were
      almost constant at caudal to L4/5 in most child subjects, especially in younger
      children. Comparison of MEP latencies with the peripheral motor conduction times
      by the F technique suggests that the proximal sites of excitation of the nerve
      root are 0.0-0.6 ms conduction times distal to the motoneuron, while the distal
      sites of excitation are 2.1-2.9 ms conduction times distal to the motoneuron. We
      conclude that performing MS using the 8-shaped coil enables us to excite the
      nerve roots near the motoneuron as well as those near the intervertebral foramen,
      and that MEPs are elicited more easily in younger children than in adolescents
      and adults.

PMID- 9152203
TI  - Silent period in upper limb muscles after noxious cutaneous stimulation in man.
AB  - We studied the effect of electrical stimulation of the C5-C8 dermatomes on
      voluntary electromyographic activity (EMG) recorded from the ipsilateral first
      dorsal interosseus (FDI), abductor digiti minimi, flexor and extensor carpi,
      triceps brachii, biceps brachii, and orbicularis oculi muscles of healthy humans.
      Finger stimulation (C6-C8) produced an EMG inhibition (silent period, SP), which
      progressively decreased in duration from distal to proximal muscles; in the
      biceps it induced a slight facilitation and in the orbicularis oculi muscle, it
      had no effect. Stimulation of the C5 dermatome induced no response in either
      distal or proximal muscles. Only high-intensity stimuli evoked clear silent
      periods. The threshold for evoking an SP was almost double that required for
      sensory action potentials, 3.25 times the sensory threshold, and decidedly above
      the pain threshold. An indirect estimation of the conduction velocity of SP
      afferent fibres placed them in the A-delta group of myelinated fibres. In double
      shock experiments, used to study the recovery cycle of the SP in the FDI muscle
      after finger stimulation, neither low- nor high-intensity conditioning stimuli
      delivered 100-500 ms before the test stimulus changed test SPs. Experiments
      designed to evaluate motoneuronal excitability showed that in relaxed FDI muscle,
      finger stimulation markedly reduced the F wave at the 50 ms time interval, the
      time when the SP normally occurs. Our findings demonstrate that the activation of
      A-delta afferents from the fingers inhibits the C7-T1 motoneurons
      postsynaptically, through an oligosynaptic spinal circuit. We propose that the
      strong inhibitory effect exerted by noxious cutaneous stimuli on all distal
      muscles may contribute to a defence action which is specific for the human upper
      limb.

PMID- 9152204
TI  - A new method for reproducible coil positioning in transcranial magnetic
      stimulation mapping.
AB  - A new method is presented for mapping the motor cortex by transcranial magnetic
      stimulation in which the position of the stimulation coil on the scalp is
      measured using a 3D digitizer. The reproducibility of the method was tested by
      mapping 3 times the left abductor digiti minimi of 6 right-handed subjects and
      calculating the position of the centre of gravity (CoG), the area and volume of
      the individual maps. For individual maps, the coordinates of the CoG were found
      to be reproducible within +/-3 mm and the map areas and normalized volumes to
      within +/-20%, when the induced current flows anteriorly. Six more subjects were
      mapped to estimate interindividual variability of the position of the CoG. The
      method's ability to differentiate the cortical representation of two close
      muscles was successfully tested by mapping the flexor carpi radialis and the
      biceps brachii in another subject. Coordinates are given in a Cartesian frame of
      reference defined by the two tragi and the nasion. This feature will facilitate
      the comparison of results and their superposition on MR images.

PMID- 9152205
TI  - Effects of vigabatrin on motor potentials evoked with magnetic stimulation.
AB  - We studied the effect of an acute loading dose of vigabatrin on threshold of
      motor responses and duration of silent period elicited with cortical magnetic
      stimulation in normal subjects. In contrast to phenytoin, vigabatrin does not
      increase the motor threshold of first dorsal interosseus muscle. We also show
      that, although vigabatrin increases GABA concentrations in the central nervous
      system, duration of silent period studied at various stimulus intensities is not
      modified after vigabatrin administration.

PMID- 9152206
TI  - Magnetic stimulation of the descending and ascending tracts at the foramen magnum
      level.
AB  - To test the possibility that stimulation over the foramen magnum activates
      ascending tracts as well as descending tracts, we studied 4 patients with
      myoclonic epilepsy all of whom had enhanced cortical long loop reflexes (LLRs)
      and 10 normal subjects, using our previously reported method (Ugawa et al., Ann.
      Neurol., 1994, 36: 618-624). For latency comparisons, peripheral nerve
      stimulation at the elbow and spinal motor root were also performed. In all
      patients, magnetic stimulation at the foramen magnum consistently elicited long
      loop reflexes as well as direct responses caused by stimulation of the descending
      tracts. In contrast, no LLRs were ever seen in any normal subjects. The latencies
      of both types of response were the same whether stimulation used upward or
      downward current in the brain, although the former was always more effective.
      This indicates that stimulation at the level of the foramen magnum activates
      ascending tracts as well as descending tracts at a fixed position. The threshold
      for LLRs was lower than that for activation of the descending tracts. This
      threshold difference is compatible with the hypothesis that large diameter fibers
      from muscle afferent conduct the central afferent volley for LLRs (Marsden et
      al., Brain, 1977, 100: 185-200).

PMID- 9152207
TI  - ECG-related fasciculation potential.
AB  - We report the observation of an unusual fasciculation potential (FP). This FP was
      time-locked to the electrocardiogram (ECG) in 87% of the discharges. The motor
      unit action potential (MUAP) of the FP was also elicited as H-reflex. As
      mechanism we propose spindle afferent discharges mechanically triggered by the
      arterial pulse, i.e. a reflex fasciculation. We suggest that such a heartbeat
      related mechanism could explain synchronous fasciculations described by Norris
      (Arch. Neurol., 1965, 13: 495-500).

PMID- 9152208
TI  - Comparison of soleus H-reflex gain from prone to standing in dancers and
      controls.
AB  - To examine the differences in soleus H-reflex gain between trained dancers and
      control subjects, the soleus H-reflex amplitude and background muscle activity of
      9 trained dancers (means of 20.3 +/- 2.1 years of age, and 14.3 +/- 3.8 years of
      training) and 9 control subjects (mean 23.3 +/- 3.2 years of age) were compared
      at rest and at 10, 20, and 30% of a maximal voluntary soleus contraction during
      two conditions: prone and standing. The ratio of the maximal H-reflex (H-max) to
      the maximal motor response (M-max) was also measured during both conditions.
      Correlation was performed between background EMG and the resultant H-reflex to
      determine reflex gain. The results demonstrated that the control subjects and the
      dancers displayed a similar reflex gain during the prone condition (slope = 3.30
      vs. 3.64, respectively). However, during the standing condition, dancers
      demonstrated a significantly lower reflex gain (slope = 1.78) than did control
      subjects (slop = 3.68). Furthermore, although both groups significantly decreased
      the H-max/M-max ratio from prone to standing, no differences were found between
      groups at either condition. This suggests that the differences in standing reflex
      gain between the dancers and control subjects were a product of differential
      control of reflex modulation involved in postural control. An initial hypothesis
      explaining the differences between the standing reflex gain of the groups relates
      to plasticity of central inhibitory control mechanisms, primarily presynaptic
      and/or reciprocal inhibition.

PMID- 9152209
TI  - Clinical use of polysynaptic flexion reflexes in the management of spasticity
      with intrathecal baclofen.
AB  - The aim of this study was to evaluate the clinical usefulness of lower limb
      flexion reflexes (FR) in the assessment of spinal excitability responsible for
      spontaneous or induced spasms. FR were recorded on the short head of biceps
      femoris, after electrical stimulation of the ipsilateral sural nerve at the
      ankle, in 17 spastic patients selected for chronic intrathecal administration of
      baclofen. The results obtained before and after treatment were compared with
      clinical scores commonly used to assess spasticity (Ashworth and spasm scores).
      Before intrathecal baclofen 15/17 patients (88%) had pathologically enhanced
      flexor reflexes in the lower limbs, which were associated to clinical spasms.
      Reflex enhancement was accompanied in 47% of cases by abnormal decrease of reflex
      threshold. No significant correlation appeared between the magnitude or threshold
      of FR in control conditions and either the hypertonia (Ashworth scale) or the
      number of clinical spasms per unit of time. Intrathecal baclofen attenuated
      flexor reflex amplitude and increased reflex threshold in all patients. Our
      results suggest that FR investigate the intrinsic features of the spasms
      (threshold, intensity and duration) not assessed clinically, and that therefore
      the information gathered from FR recordings is not redundant with, and adds
      significantly to, that obtained by clinical scales. In our experience, FR
      recordings appeared to be a useful tool for quantifying the benefit of
      antispastic treatment and might be used as an ancillary indicator to determine
      the minimal effective dose of intrathecal baclofen.

PMID- 9152210
TI  - Electromyographic analysis of postural responses during standing leg flexion in
      adults with hemiparesis.
AB  - The purpose of this study was to examine muscle activation patterns during
      standing leg single leg flexion in adults with hemiparesis. Specifically, the
      electromyographic activation patterns of the flexing limb biceps femoris and
      gluteus medius, and the stance limb gluteus medius muscles were analyzed as a
      function of whether the muscles were paretic or not. Delayed activation of the
      affected flexing side gluteus medius, as compared with unaffected flexing side
      gluteus medius, resulted in it being activated simultaneous with the flexing
      biceps femoris rather than preceding it as was previously found in healthy
      subjects. This suggests a temporal change in the sequential mode of coordination
      of the postural and intended components of the task. In addition, the magnitude
      of the electromyographic integrals of both the affected and unaffected flexing
      side gluteus medius in the early propulsive phase of the task was significantly
      reduced in comparison with healthy subjects. These alterations can be attributed
      to spatial alterations in the sequential form of organization or to a shift to a
      different mode of neural control in order to perform a relatively novel task.
      These results suggest a potential adaptive capacity in these individuals.

PMID- 9152211
TI  - Effects of experimental muscle pain on muscle activity and co-ordination during
      static and dynamic motor function.
AB  - The relation between muscle pain, muscle activity, and muscle co-ordination is
      still controversial. The present human study investigates the influence of
      experimental muscle pain on resting, static, and dynamic muscle activity. In the
      resting and static experiments, the electromyography (EMG) activity and the
      contraction force of m. tibialis anterior were assessed before and after
      injection of 0.5 ml hypertonic saline (5%) into the same muscle. In the dynamic
      experiment, injections of 0.5 ml hypertonic saline (5%) were performed into
      either m. tibialis anterior (TA) or m. gastrocnemius (GA) and the muscle activity
      and co-ordination were investigated during gait on a treadmill by EMG recordings
      from m. TA and m. GA. At rest no evidence of EMG hyperactivity was found during
      muscle pain. The maximal voluntary contraction (MVC) during muscle pain was
      significantly lower than the control condition (P < 0.05). During a static
      contraction at 80% of the pre-pain MVC muscle pain caused a significant reduction
      in endurance time (P < 0.043). During dynamic contractions, muscle pain resulted
      in a significant decrease of the EMG activity in the muscle, agonistic to the
      painful muscle (P < 0.05), and a significant increase of the EMG activity of the
      muscle, antagonistic to the painful muscle (P < 0.05). Muscle pain seems to cause
      a general protection of painful muscles during both static and dynamic
      contractions. The increased EMG activity of the muscle antagonistic to the
      painful muscle is probably a functional adaptation of muscle co-ordination in
      order to limit movements. Modulation of muscle activity by muscle pain could be
      controlled via inhibition of muscles agonistic to the movement and/or excitation
      of muscles antagonistic to the movement. The present results are in accordance
      with the pain-adaptation model (Lund, J.P., Stohler, C.S. and Widmer, C.G. In: H.
      Vaeroy and H. Merskey (Eds.), Progress in Fibromyalgia and Myofascial Pain.
      Elsevier, Amsterdam, 1993, pp. 311-327.) which predicts increased activity of
      antagonistic muscle and decreased activity of agonistic muscle during
      experimental and clinical muscle pain.

PMID- 9152212
TI  - Sympathetic skin responses of the hand in normal subjects: shorter latency at
      distal phalanx.
AB  - We studied the conduction of the sympathetic skin response (SSR) in the hands of
      35 normal subjects by simultaneous recording at five sites. The mean latency of
      the SSR in all subjects increased from the wrist (W) to the middle phalanx (M),
      but the SSR latency at the distal phalanx (D) was shorter than that at the middle
      phalanx. The mean conduction time and conduction velocity from W to M was 197.5
      ms and 0.87 m/s, respectively, and that from W to D was 48.8 ms and 2.34 m/s,
      respectively. For evaluation of the cause of the shorter latency at D, digital
      nerve blocking was performed in two subjects. The blocking of the volar digital
      nerves at the proximal phalanx abolished SSR at M and D. It was postulated that
      the initiation or conduction of sudomotor nerve impulse to the distal phalanx
      would be facilitated compared with those to the other proximal sites in the hand.
      The SSR conduction time between W and M may be a means of detecting alteration of
      sympathetic sudomotor nerve activity.

PMID- 9152213
TI  - George Bush did it right with parachute jump.

PMID- 9152214
TI  - Geriatrics photo quiz. Multi-infarct dementia.

PMID- 9152215
TI  - Springtime eruption on the hands.

PMID- 9152217
TI  - Urinary stone disease: a practical guide to metabolic evaluation.
AB  - Urolithiasis is the third most common affliction of the urinary tract, after
      infections and diseases of the prostate. Approximately 10% of the North American
      population will have at least one urinary calculus by age 70. A thorough history
      and physical examination will usually confirm the diagnosis of urinary stone
      disease. A simplified laboratory evaluation may be performed for patients with a
      single stone episode. A more extensive evaluation is required for patients with
      recurrent, metabolically active stones and patients at high risk (ie, cystine
      stone formers and those who develop bladder dysfunction or nephrosclerosis).
      Intravenous pyelography with tomography remains the gold standard for imaging of
      the urinary tract to confirm the diagnosis and formulate a treatment plan.

PMID- 9152216
TI  - Viral hepatitis: how to manage type C and D infections.
AB  - Hepatitis C and D are relative newcomers to the study of viral hepatitis. Their
      transmission is mainly parenteral. The 0.5 to 2.2% prevalence of hepatitis C in
      the United States does not vary by patient age. Often, hepatitis C is
      asymptomatic. In older patients, symptomatic infection has a cholesteatic
      appearance, and progress to chronic hepatitis and cirrhosis is more rapid than in
      younger adults. Hepatitis D virus is a defective single-stranded RNA that
      presents as a co-infection or superinfection of hepatitis B. Prevalence varies by
      geographic region. The rate of progression to chronic disease and cirrhosis is
      high in superinfection.

PMID- 9152218
TI  - Nursing home visits: an efficient system for the busy physician.
AB  - For their patients who enter a nursing home, physicians need to know how to
      perform an efficient and effective visit. With a structured, methodical approach
      the initial and follow-up visits can be done within 15 minutes per patient. Each
      visit can include review of diagnoses and medications; input from the patient,
      nursing staff, and families; vital signs and weights; physical exam; lab results;
      and review of the interdisciplinary care plan. An assessment that genuinely
      contributes to the care plan will enhance the physician's effectiveness and
      satisfaction in long-term care practice.

PMID- 9152219
TI  - Exercise at midlife: how and why to prescribe it for sedentary patients.
AB  - Moderate exercise for middle-aged and older adults is emerging as an important
      adjuvant to the treatment of many diseases. These include cardiovascular disease,
      diabetes, osteoporosis, osteoarthritis, insomnia, deconditioning, and (to a
      degree) obesity. A recent report from the United States Surgeon General
      recommends that most adults exercise most if not all days of the week,
      accumulating 180 minutes of moderate intensity exercise weekly. If your patients
      have been previously sedentary, encourage them to start a slow, stepwise exercise
      program. Ongoing support, encouragement, and follow-up can help them commit to
      and maintain a program of regular exercise.

PMID- 9152220
TI  - Atypical presentation of colon perforation related to corticosteroid use.

PMID- 9152222
TI  - Animal handling.

PMID- 9152223
TI  - cDNA library.

PMID- 9152224
TI  - Evaluation of the gene encoding the tissue inhibitor of metalloproteinases-3 in
      various maculopathies.
AB  - PURPOSE: Mutations in the gene encoding the tissue inhibitor of
      metalloproteinases-3 (TIMP3) have been shown previously to cause Sorsby's fundus
      dystrophy, an autosomal-dominant disorder characterized by extracellular matrix
      irregularities in Bruch's membrane. To assess the involvement of TIMP3 in a
      variety of other macular dystrophies, the authors have screened this gene for
      disease-causing mutations in age-related macular degeneration (AMD), adult
      vitelliform macular dystrophy (AVMD), central areolar choroidal dystrophy (CACD),
      syndrome-associated macular dystrophies, cone-rod dystrophy, and a group with
      unspecified macular degeneration. METHODS: Single-stranded conformational
      analysis of the entire coding region was performed using the polymerase chain
      reaction and oligonucleotide primers flanking the five exons of the TIMP3 gene as
      well as the putative promotor region and a highly conserved fragment of the 3'
      untranslated region. The authors analyzed a total of 217 patients, including 143
      patients with AMD, 28 patients with AVMD, 21 patients with CACD, and 25 patients
      with other forms of macular dystrophy. RESULTS: In the 217 patients analyzed, the
      authors have identified one sequence alteration (a G-to-C base change) in the 5'
      untranslated region in a patient with AMD. However, the functional consequences
      of this mutation are not clear. No other disease-causing mutations were found.
      The authors have characterized a frequent intragenic polymorphism in exon 3 of
      the TIMP3 gene (heterozygosity = 0.57) that will be useful for genetic linkage or
      allele sharing analyses or both. CONCLUSIONS: The authors' results suggest that
      TIMP3 is not a major factor in the cause of AMD, AVMD, and CACD. Thus far,
      Sorsby's fundus dystrophy appears to be the only phenotype known to be associated
      with mutations in TIMP3.

PMID- 9152225
TI  - Exclusion of TIMP3 as a candidate locus in age-related macular degeneration.
AB  - PURPOSE: Age-related macular degeneration (AMD) is a genetically complex
      disorder. Tissue inhibitor of metalloproteinases-3 (TIMP3) on chromosome 22 has
      been identified as a gene that is mutated in Sosby's fundus dystrophy, an
      autosomal-dominant macular dystrophy that phenotypically resembles AMD. The
      purpose of this study was to determine whether TIMP3 is a major susceptibility
      gene for the AMD phenotype. METHODS: Thirty-eight multiplex families with AMD
      were identified in Massachusetts and North Carolina. The macular findings were
      graded according to a modification of the grading system used in the Age-Related
      Eye Disease Study, and persons with extensive intermediate drusen, any large
      drusen, geographic atrophy, or evidence of exudative maculopathy were coded as
      affected for the purpose of the analysis. Linkage analysis was performed using
      both model-dependent (lod score) and model-independent (sibpair) methods. For the
      lod score analysis, both autosomal-dominant as well as recessive low penetrance
      "affecteds only" analyses were examined. Three markers, D22S280, D22S529, and
      D225268, linked tightly and flanking the TIMP3 locus, were chosen for the
      analysis. Association studies were performed by examining one randomly chosen
      affected person per family and comparing the patients with AMD with a series of
      age, gender, and ethnically matched control subjects with no known history of
      AMD. RESULTS: Lod score analysis excluded linkage in these data for an
      approximately 10-cm interval surrounding the TIMP3 gene for all models tested. In
      addition, no significant findings were observed with either the sibpair or the
      association study. CONCLUSIONS: No evidence of linkage or association or both was
      found between AMD and TIMP3 in these 38 families. These data suggest that
      although clinically similar, the genetic defect in Sorsby's fundus dystrophy is
      of a different cause than the majority of the genetic causes of AMD.

PMID- 9152226
TI  - Efficacy of treatment after measurable diabeticlike retinopathy in galactose-fed
      rats.
AB  - PURPOSE: To determine whether the diabeticlike retinal microangiopathies of the
      galactose-fed rat model could be ameliorated if intervention by withdrawal of the
      galactose diet or treatment with the aldose reductase inhibitor AL-3152 was
      initiated after quantifiable microangiopathies had occurred. METHODS: Weanling
      male Sprague-Dawley rats were randomized into five groups and fed for up to 24
      months Purina laboratory chow (#5001) plus 50% starch (control [CON]), 50% D
      galactose (galactose [GAL]), 50% D-galactose with AL-3152 (approximately 14 mg/kg
      per day) (prevention [PRV]), 50% D-galactose for 6 months followed by
      intervention with the inhibitor (intervention [INT]), or 50% D-galactose for 6
      months followed by replacement with the 50% starch diet (withdrawal [GWD]). In
      rats on experimental diets and killed after 6, 18, and 24 months, one retina was
      prepared for transmission electron microscopy; the other was used for vessel
      wholemounts using elastase digestion. Capillary images were analyzed by computer
      morphometry. RESULTS: At 6 months, the GAL rats exhibited statistically
      significant (P < 0.05) increases over CON rats in mean capillary basement
      membrane thickness, capillary density, and dilated channels. These parameters
      tended to increase with time in most groups, and the differences between GAL and
      age-matched CON rats were maintained at the 18- and 24-month endpoints. Although
      the microangiopathies were ameliorated by AL-3152 treatment from the onset (PRV),
      intervention after 6 months of galactosemia with either galactose withdrawal
      (GWD) or addition of inhibitor (INT) showed amelioration in only some parameters
      at 18 months and no statistically significant benefit at the 24-month endpoint.
      CONCLUSIONS: Amelioration of galactose-induced retinal microangiopathies with AL
      3152 in the prevention group suggests an efficacious application of aldose
      reductase inhibitors in treating diabetic retinopathy, provided treatment can
      begin soon after the onset of diabetes. Intervention after some of the earliest
      microscopic lesions neither halted progression of the angiopathy nor provided
      appreciable benefit at the 24-month follow-up.

PMID- 9152227
TI  - Mutation of a conserved cysteine in the X-linked cone opsins causes color vision
      deficiencies by disrupting protein folding and stability.
AB  - PURPOSE: To test the effects of disruption of a conserved cysteine in the green
      cone opsin molecule on light-activated isomerization, transducin activation,
      folding, transport, and protein half-life. METHODS: Stable cell lines were
      established by transfecting 293-EBNA cells with a plasmid containing wild-type or
      mutant (C203R, C203S, C126S, C126S/C203S) green opsin cDNA molecules. The
      proteins were induced by culturing the cells in the presence of cadmium chloride
      and analyzed by spectra, transducin activation, Western blotting, pulse-labeling
      with immunoprecipitation, and immunocytochemistry. RESULTS: The C203R mutation
      disrupts the folding and half-life of the green opsin molecule and its abilities
      to absorb light at the appropriate wavelength and to activate transducin. Similar
      disruption of folding, half-life, and light activation occurs when Cys203 or its
      presumed partner for formation of a disulfide bond (Cys126) is replaced by serine
      residues. CONCLUSIONS: Like rhodopsin, the folding of the cone opsins appears to
      be dependent on the formation of a disulfide bond between the third transmembrane
      helix and the second extracellular loop. Disruption of this disulfide bond
      represents a cause of color vision deficiencies that is unrelated to spectral
      shifts of the photopigment.

PMID- 9152228
TI  - Serum inhibits tight junction formation in cultured pigment epithelial cells.
AB  - PURPOSE: These experiments were designed to characterize tight junction formation
      by retinal pigment epithelial (RPE) cells in vitro and to compare the effects on
      this process of hormonally defined medium (HDM) and serum-containing medium.
      METHODS: Formation of RPE tight junctions was analyzed in freshly isolated rat
      RPE cells maintained either in HDM or serum-containing medium. Junctions were
      evaluated functionally by measuring transepithelial electrical resistance (TER)
      and permeability and structurally by immunolocalization of the junction
      associated actin microfilaments. Calcium dependency of the junctions was
      determined by reducing media calcium concentration. RESULTS: RPE cells cultured
      in serum-free HDM developed calcium-dependent tight junctions, which exhibited
      TER levels > 150 omega cm2 and low paracellular permeability. Serum-containing
      media inhibited tight junction formation as indicated by significant reductions
      in TER and increases in permeability. Junction-associated actin microfilaments
      and cell density were unchanged. CONCLUSIONS: Tight junction formation by RPE
      cells is inhibited by serum. This activity may play an important role in
      responses of the RPE layer to injury, contributing to the pathologic progression
      of blood-retinal barrier dysfunction.

PMID- 9152229
TI  - Clinicopathologic correlation of localized retinal pigment epithelium
      debridement.
AB  - PURPOSE: To characterize changes in the retina, retinal pigment epithelium (RPE),
      and choriocapillaris with fluorescein angiography (FA) and histology after
      hydraulic or abrasive RPE debridement in 26 domestic short-haired cats. METHODS:
      Hydraulic debridement was produced by injecting balanced salt solution forcefully
      into the subretinal space. For abrasive debridement, RPE were removed with a
      silicone-tipped cannula after creating a localized retinal detachment. The FAs
      were performed after surgery, and tissue was prepared for light microscopy (LM)
      and scanning electron microscopy (SEM). RESULTS: Sixty-seven blebs were examined
      by FA 1 hour after surgery, and RPE debridement was confirmed by SEM or LM in 15
      blebs from 10 animals. Hyperfluorescence and variable central fluorescein leakage
      were seen 1 week after surgery in 52 of 53 blebs (which includes all 27 blebs
      from the 1-week timepoint and 26 of 29 blebs from the 4-week timepoint that were
      studied by FA 1 week after surgery). Choriocapillary filling delays were seen in
      no hydraulic debridements, but in 11 of 14 abrasive blebs, especially in areas
      showing leakage late in the angiogram. In 1 of 13 hydraulic and 12 of 14 abrasive
      debridements, areas of late dye leakage had no RPE with outer retinal
      degeneration. At the 4-week timepoint, 1 of 17 hydraulic and 10 of 12 abrasive
      debridements had foci of delayed or absent choriocapillary perfusion by FA, with
      degenerated outer retina, no RPE, and choriocapillary atrophy by histologic
      analysis. CONCLUSIONS: Abrasive debridement is more commonly associated with
      abnormal FAs and with incomplete RPE repopulation, choriocapillaris atrophy, and
      outer retinal degeneration than is hydraulic debridement. This clinicopathologic
      study may give insight into FA interpretation after choroidal neovascular
      membrane removal in human patients.

PMID- 9152230
TI  - Reattachment of cultured human retinal pigment epithelium to extracellular matrix
      and human Bruch's membrane.
AB  - PURPOSE: To determine the mechanism of reattachment of harvested human retinal
      pigment epithelium (RPE) to RPE-derived extracellular matrix and Bruch's
      membrane. METHODS: Confluent first-to third-passage human RPE were harvested from
      tissue culture and plated onto RPE-derived extracellular matrix or human Bruch's
      membrane exoplants denuded of cells by treatment with 0.02 N ammonium hydroxide.
      The authors measured RPE reattachment to uncoated surfaces or surfaces precoated
      with extracellular matrix proteins (fibronectin, laminin, vitronectin, or type IV
      collagen), antibodies to extracellular matrix-proteins, or the synthetic peptide
      RGDS (arginine-glycine-aspartate-serine). Some RPE were pretreated with anti-beta
      1 integrin antibodies before plating onto either substrate. RESULTS: Coating the
      surface of either RPE-derived extracellular matrix or Bruch's membrane with
      fibronectin, laminin, vitronectin, or type IV collagen increased the RPE
      attachment rate. Exposing RPE to anti-beta 1 integrin antibodies or RGDS or
      precoating the surface with antibodies to fibronectin, laminin, vitronectin, or
      type IV collagen decreased the RPE attachment rate to both surfaces. The RPE
      attachment rate to Bruch's membrane was lower when the exoplants were harvested
      from the macula of older (age, 70 to 90 years) versus younger (age, 30 to 40
      years) persons (52.4 +/- 3.6% versus 64.3 +/- 3.5%, respectively; P < 0.05).
      CONCLUSIONS: The attachment of cultured human RPE cells to human Bruch's membrane
      or to RPE-derived extracellular matrix is mediated by an interaction between the
      beta 1-subunit of integrin on the RPE surface and ligands in the extracellular
      matrix that include laminin, fibronectin, vitronectin, and type IV collagen. The
      lower rate of RPE reattachment to the macula from older human cadaveric eyes may
      have implications for studies aimed at RPE transplantation in elderly persons.

PMID- 9152231
TI  - Matrix stimulates the proliferation of human corneal endothelial cells in
      culture.
AB  - PURPOSE: Extracellular matrices were tested for their ability to support the
      adhesion and proliferation of human corneal endothelial cells. METHODS: Human
      corneal endothelial cells were plated onto tissue culture dishes coated with
      purified fibronectin or a matrix elaborated by cultured bovine corneal
      endothelial cells. The presence of human cells in the cultures was confirmed by
      karyotyping. Cell size at increasing passage number was analyzed, and cellular
      response to growth factors was assessed using a 96-well microtiter plate assay.
      RESULTS: When tissue culture dishes were coated with fibronectin, the cells
      attached to the dish but grew slowly. Human corneal endothelial cells plated onto
      the matrices elaborated by bovine corneal endothelial cells attached to the
      culture dish and grew to fill the flask. At confluence, the cells had a hexagonal
      morphology similar to that seen in vivo. Karyotype analysis showed that the cells
      were of human and not bovine origin. The time required for senescence in culture
      was dependent on the age of the donor cornea. The bovine matrices enhanced the
      proliferative response of human corneal endothelial cell cultures to endothelial
      cell growth supplement and keratinocyte growth factor. Epidermal growth factor
      and hepatocyte growth factor stimulated human cell proliferation in a dose
      dependent fashion, regardless of the substratum on which the cells were plated.
      CONCLUSIONS: The use of substratum elaborated by bovine corneal endothelial cells
      has proved useful in the preparation of human endothelial cell cultures from
      juvenile and adult donors. The method has been used to establish cultures from
      more than 50 donors from age 1 day to 76 years.

PMID- 9152232
TI  - Murine orthotopic corneal transplantation in high-risk eyes. Rejection is
      dictated primarily by weak rather than strong alloantigens.
AB  - PURPOSE: Using a model of orthotopic corneal transplantation in which allografts
      were placed in normal eyes of mice, the authors previously reported that grafts
      bearing minor H antigens alone are more likely to be rejected (approximately 50%)
      than are grafts displaying only major histocompatibility (MHC) alloantigens
      (20%). These studies have been extended to include corneal grafts placed in
      neovascularized high-risk eyes of recipient mice. METHODS: Neovascularization was
      induced by placing sutures in the central cornea of one eye of recipient mice.
      Two weeks later, MHC class I only, class II only, minor H only, or MHC+minor H
      disparate corneas were grafted into these sutured eyes, and their rejection rates
      were examined. RESULTS: Although MHC+minor H disparate corneal allografts were
      rejected uniformly in neovascularized graft beds in 12 (100%) of 12, MHC class I
      only disparate grafts were rejected in 8 (66.7%) of 12 and MHC class II only
      disparate corneal allografts were rejected in 7 (58.3%) of 12. Surprisingly, the
      rejection rate of minor H only disparate corneal allografts was 10 (90.9%) of 11.
      CONCLUSIONS: These findings indicate that for orthotopic corneal allografts
      placed in high-risk graft beds, minor H antigens offer a more formidable barrier
      to graft acceptance than do MHC-encoded antigens. The authors speculate that this
      unexpected outcome may reflect a reduced level of MHC expression on corneal
      tissue. Moreover, because the cornea as a graft lacks bone marrow-derived
      dendritic cells, allorecognition by recipient T cells must occur by way of the
      indirect pathway of alloantigen processing, and in this situation, minor H
      antigens may compete favorably with MHC antigens for presentation by recipient
      antigen-presenting cells that infiltrate the graft.

PMID- 9152233
TI  - Epidermal growth factor stimulation of phosphatidylinositol 3-kinase during wound
      closure in rabbit corneal epithelial cells.
AB  - PURPOSE: To determine whether there is an association between epidermal growth
      factor (EGF)-induced activation of phosphatidylinositol 3-kinase (PI 3-kinase)
      and stimulation of wound closure in rabbit corneal epithelial cells. METHODS:
      Immortalized rabbit corneal epithelial cells were cultured in 24-well plates
      until they became confluent. Circular wounds were created in confluent cultures
      by cell denudation and then incubated in the absence and presence of EGF for
      varying intervals. Wound closure was monitored by staining the cells with Giemsa
      and quantifying the wound area with SigmaS can computer program. Cell
      proliferation during wound repair was estimated by measuring the incorporation of
      [3H]thymidine into nuclear DNA. Changes in PI 3-kinase activity were assessed by
      measuring the production of phosphatidylinositol 3,4,5-triphosphate [PI(3,4,5)P3]
      in 32P-labeled cells as well as by immunoprecipitating and assaying PI 3-kinase
      activity with phosphatidylinositol 4,5-bisphosphate and [gamma-32P]ATP as
      substrates. The enzyme product, PIP3, was analyzed by a combination of thin-layer
      and high-pressure liquid chromatography. RESULTS: Addition of 10 ng/ml EGF to the
      wounded corneal epithelial cells stimulated wound closure in a time-dependent
      manner, and the wound closed completely within 48 hours. The effect of EGF was
      dose dependent, and maximal wound closure occurred at 10 ng/ml EGF. As the
      epithelial cells were undergoing EGF-stimulated wound closure, there was a time
      dependent increase in PI 3-kinase activity. The enzyme activity increased
      maximally at 24 hours and then decreased gradually as the incubation was
      continued to 48 hours. When the cells were treated with wortmannin, a PI 3-kinase
      inhibitor, the EGF-stimulated PIP3 formation as well as the wound closure were
      inhibited significantly. Treatment of the cells with genistein or tyrphostin B42
      also decreased both EGF-stimulated PIP3 formation and wound closure in a dose
      dependent manner. Concomitant with stimulation of wound repair, the growth factor
      increased [3H]thymidine incorporation into nuclear DNA, and this effect was
      inhibited by pretreatment of the cell with wortmannin. CONCLUSIONS: The data
      suggest a close correlation between EGF-stimulated wound closure and activation
      of PI 3-kinase in corneal epithelial cells. It can be concluded that PI 3-kinase
      might be an important component in signal transduction cascade initiated by EGF
      receptor interaction, which leads to mitosis and cell proliferation during wound
      closure in corneal epithelial cells.

PMID- 9152234
TI  - Differential induction of GRO alpha gene expression in human corneal epithelial
      cells and keratocytes exposed to proinflammatory cytokines.
AB  - PURPOSE: GRO alpha is an inducible neutrophil chemotactic factor synthesized in
      inflamed corneal tissues. In this study, the regulation of GRO alpha synthesis
      after exposure of human corneal cells to proinflammatory cytokines was
      investigated. METHODS: Pure cultures of human corneal epithelial cells and
      keratocytes were exposed to increasing concentrations of either interleukin-1
      alpha (IL-1 alpha) or tumor-necrosis factor-alpha (TNF-alpha). At selected times
      postexposure, the amounts of GRO alpha produced by the cultures were quantitated
      by enzyme-linked immunosorbent assay. The RNA was harvested from stimulated
      cultures to monitor GRO alpha mRNA and pre-mRNA levels by the reverse
      transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Both IL-1 alpha and
      TNF-alpha induced significant levels of GRO alpha synthesis in keratocytes.
      However, IL-1 alpha-stimulated cells produced > 10 times more GRO alpha protein
      and 12 times more GRO alpha mRNA than did TNF-alpha-stimulated keratocytes. In
      contrast to the log differences in mRNA levels and protein synthesis, there was a
      less than twofold difference between IL-1 alpha and TNF-alpha in their capacity
      to induce GRO alpha specific pre-mRNA synthesis. When actinomycin D was added to
      stimulated keratocytes to inhibit transcription, the half-life of GRO alpha mRNA
      in TNF-alpha-treated cells was < 1 hour, whereas the half-life of the GRO alpha
      mRNA synthesized in IL-1 alpha-stimulated cells was > or = 9 hours. In contrast
      to keratocytes, exposure of corneal epithelial cells to IL-1 alpha and TNF-alpha
      did not induce significant increases in steady-state levels of GRO alpha pre
      mRNA, mRNA, or protein. CONCLUSIONS: The results suggest that keratocytes are the
      major producers of GRO alpha in the human cornea. The capacity of IL-1 alpha to
      stimulate the synthesis of significantly higher quantities of GRO alpha in
      keratocytes compared to TNF-alpha is caused by the fact that GRO alpha-specific
      transcripts are more than nine times more stable in cells exposed to IL-1 alpha
      than in cells exposed to TNF-alpha.

PMID- 9152236
TI  - Quantification of oxygen-induced retinopathy in the mouse.
AB  - PURPOSE: To describe a quantifiable model of vascular proliferation in oxygen
      induced retinopathy (OIR) in the mouse. METHODS: Neonate Quackenbush mice were
      subjected to high-ambient oxygen (approximately 95%) for the first 5 days after
      birth, effecting a total inhibition of retinal vascular growth. Animals then were
      returned to room air, and the rates of subsequent vascular development in the
      plane of the retina and estimates of retinal capillary density were measured from
      flatmounts of ink-perfused eyes. Observations were confirmed with fluorescein
      isothiocyanate-lectin labeling of the peripheral vasculature. Abnormal growth of
      vascular sprouts into the vitreous was recorded from cross-sections. Observations
      in OIR were compared against those of age-matched control animals. RESULTS: The
      slower rate of retinal revascularization in OIR mice was quantified and compared
      against the normal rate. Lectin-binding studies confirmed the reliability of ink
      preparations. The number of vitreous sprouts in OIR peaked 8 to 10 days after
      animals were returned to room air (13 to 15 postnatal days). Sprouts then
      regressed, to disappear by postnatal day 20. In all respects, bar a slightly
      lower peripheral capillary density, the normal retinal vascular pattern was
      achieved in OIR within 15 days of exposure to room air (as opposed to the 10 days
      required in control mice). CONCLUSIONS: The protocol described for quantifying
      retinal proliferation in mouse OIR is reproduced readily, and the data recorded
      here will allow the effectiveness of subsequent treatments that may affect
      retinal vascular growth to be evaluated better.

PMID- 9152235
TI  - Macrophage receptors for lumican. A corneal keratan sulfate proteoglycan.
AB  - PURPOSE: Keratan sulfate proteoglycans (KSPGs) of the cornea exhibit a
      characteristic change in glycosylation resulting from stromal inflammation and
      scarring. To examine potential roles for these molecules in the pathobiology of
      the cornea, the authors investigated interaction of inflammatory macrophages with
      KSPGs in vitro. METHODS: Attachment and spreading of mouse peritoneal macrophages
      were examined on surfaces coated with corneal proteoglycans, intact or with
      modified glycosylation. Solution-phase interactions were demonstrated using
      soluble proteoglycans labeled with 125I-Iodine or with fluorescein. The affinity
      and specificity of these interactions were determined by competitive inhibition
      with unlabeled proteoglycans. RESULTS: Macrophages did not adhere to intact
      corneal KSPGs but did attach and spread rapidly on the lumican core protein after
      the removal of keratan sulfate chains. Arterial lumican, a nonsulfated form of
      this proteoglycan, also stimulated macrophage attachment. Labeled arterial
      lumican specifically bound to macrophages with high affinity. Flow cytometry
      demonstrated a high proportion of macrophages binding lumican. Lumican binding
      was inhibited by divalent cation-chelators and by polyanions. Inhibition and
      kinetics of lumican binding were distinct from interaction of macrophages with
      maleated bovine serum albumin, collagen, laminin, and fibronectin. CONCLUSIONS:
      The highly sulfated KSPGs of cornea do not promote macrophage adhesion; however,
      the low-sulfate lumican present in pathologic corneas may act to localize
      macrophages in regions of inflammation. The lumican receptor differs from
      macrophage scavenger receptors and from receptors for several other extracellular
      matrix molecules.

PMID- 9152237
TI  - Dark-adapted thresholds in children with histories of mild retinopathy of
      prematurity.
AB  - PURPOSE: To test the hypothesis that rod-mediated visual thresholds at 10 degrees
      eccentricity are elevated in children with histories of mild retinopathy of
      prematurity (ROP). METHODS: Dark-adapted thresholds for detection of 50 msec, 2
      degrees diameter spots at a 10 degrees eccentric site, and at a peripheral
      reference site, 30 degrees eccentric, were measured in 20 children with a history
      of mild ROP and known courses of refractive development. Ten myopic control
      subjects also were tested. The thresholds of the ROP and control subjects were
      compared. RESULTS: Six of the subjects with ROP had elevated thresholds at the 10
      degrees site. High myopia had been present since age 18 months or younger in each
      of the six. The thresholds of all other subjects with ROP, whose courses of
      refractive development had been toward emmetropia, and the control subjects with
      myopia were normal. In subjects with ROP, the association of early, persistent
      high myopia and an elevated threshold at 10 degrees was significant (chi 2 = 20;
      P < 0.01). Among the subjects with ROP, refractive error and axial length were
      correlated. CONCLUSIONS: ROP or factors causing ROP appear to alter rod-mediated
      retinal function. The association of abnormal rod-mediated sensitivity and
      refractive development suggests that rod-mediated retinal function is involved in
      the regulation of eye growth in children with a history of mild ROP.

PMID- 9152238
TI  - Ocular fundus morphology in preterm children. Influence of gestational age, birth
      size, perinatal morbidity, and postnatal growth.
AB  - PURPOSE: To determine the influence of gestational age, birth size, perinatal
      morbidity, and postnatal growth on fundus morphology in preterm children using
      digital image analysis of fundus photographs. METHODS: Thirty-nine preterm
      children (mean postmenstrual gestational age, 29.1 weeks; range, 24.6 to 32) were
      included in the study. Thirty-nine healthy children, born at term, were used as
      control subjects. Fundus photographs were obtained at a mean age of 4.8 years
      (preterm) and 6.1 years (control subjects). RESULTS: There was no difference in
      optic disc, excavation, or peripapillary crescent area between the two groups. In
      the group of preterm children, a large optic disc size was associated with a low
      birth weight (rs = -0.29, P = 0.07), duration of assisted ventilation (rs = 0.43,
      P = 0.006), and number of blood transfusions (rs = 0.33, P = 0.04). The girls
      born prematurely showed a negative relation between the length of gestation and
      the area of the optic disc (r2 = 0.28, P = 0.009). No such relation was found in
      boys. The preterm children had increased tortuosity of retinal vessels (P < 0.001
      and P < 0.002 for arteries and veins, respectively) and reduced number of
      vascular branching points (P < 0.001) compared with those of the control
      subjects. There were no associations between these vascular abnormalities and the
      perinatal and postnatal variables studied. CONCLUSIONS: No difference in optic
      disc morphology between preterm children and control subjects was found. However,
      preterm birth seems to affect the retinal vascular pattern close to the optic
      disc, independently of retinopathy of prematurity. Among the girls born preterm,
      optic disc size was negatively correlated to gestational age.

PMID- 9152239
TI  - Genistein, a protein tyrosine kinase inhibitor, ameliorates retinal degeneration
      after ischemia-reperfusion injury in rat.
AB  - PURPOSE: The authors sought to determine the effect of genistein, a naturally
      occurring protein tyrosine kinase inhibitor, in a model of ischemia-reperfusion
      injury in the rat retina. METHODS: Ischemia-reperfusion injury was induced by
      temporary optic nerve ligation. A dose of 0.034 mg, 0.34 mg, and 3.4 mg of
      genistein or dimethyl sulfoxide (DMSO) alone was injected intraperitoneally 1
      hour before the ligation of the optic nerve and just after the start of
      reperfusion. After 48 hours of reperfusion, the effect of genistein on overall
      protein tyrosine phosphorylation in the retina was studied using Western blot
      analysis. After 168 hours, the effect of increasing doses of genistein on retinal
      degeneration was examined by quantitative morphometric analysis of histologic
      sections of the retina. RESULTS: The authors found that tyrosine phosphorylation
      was increased after 48 hours of reperfusion in the ischemia-reperfusion-injured
      eyes treated with DMSO alone. A severe inner retinal degeneration was observed in
      the animals treated with DMSO alone after 168 hours of reperfusion. The treatment
      with 3.4 mg genistein inhibited the increase in tyrosine phosphorylation and
      protected the eyes significantly from the induced ischemic retinal degeneration
      by morphometric analysis of the mean thickness of the inner limiting membrane to
      the outer limiting membrane, the inner plexiform layer, and the inner nuclear
      layer (P < 0.02). Treatments with lower amounts of genistein (0.034 mg and 0.34
      mg) did not show a significant protection of retinal degeneration after the
      injury. CONCLUSIONS: Systemic administration of high dose of genistein, a dietary
      derived isoflavone, can ameliorate an ischemia-reperfusion-induced retinal
      degeneration. Genistein may be useful to prevent neuronal degeneration in the
      inner retina as a result of ischemic injury.

PMID- 9152240
TI  - Increase of manganese superoxide dismutase, but not of Cu/Zn-SOD, in experimental
      optic neuritis.
AB  - PURPOSE: To evaluate the role of manganese superoxide dismutase (Mn-SOD) and
      copper/zinc superoxide dismutase (Cu/Zn-SOD) in cellular protection of the optic
      nerve against the oxidative injury that contributes to demyelination in
      experimental allergic encephalomyelitis (EAE). METHODS: Immunocytochemistry for
      Mn-SOD and Cu/Zn-SOD and ultracytochemical localization of hydrogen peroxide
      (H2O2) were performed on the optic nerves of guinea pigs with EAE and normal
      guinea pigs. Cell-specific enzyme expression of SOD was quantitated by
      computerized morphometric analysis. RESULTS: Light microscopy showed a
      perivascular distribution of Mn-SOD-positive cells in the optic nerves of animals
      with EAE. Electron microscopy showed that the Mn-SOD immunogold was confined
      exclusively to mitochondria, whereas Cu/Zn-SOD immunogold was found in the
      cytoplasmic matrix and nucleus of cells of the optic nerve in both animals with
      EAE and normal animals. Results of quantitative analysis of the optic nerves of
      animals with EAE showed an 8-fold increase in Mn-SOD immunogold in astroglial
      cells and a 13-fold increase in microglial/phagocytic cells in comparison with
      that of normal animals. Increases in Mn-SOD immunogold were contiguous to H2O2
      derived reaction product. No increases in Cu/Zn-SOD immunogold were detected in
      EAE. CONCLUSIONS: Increases in Mn-SOD activity in astroglial cells and
      microglial/phagocytic cells may contribute to the relative sparing of these cells
      from injury in EAE, whereas the low level of Mn-SOD in oligodendroglial cells and
      axons may increase their vulnerability to the effects of superoxide-induced
      oxidative injury that results in demyelination.

PMID- 9152241
TI  - Nonneutralizing antibody against the glycoprotein K of herpes simplex virus type
      1 exacerbates herpes simplex virus type-1-induced corneal scarring in various
      virus-mouse strain combinations.
AB  - PURPOSE: To determine whether the exacerbation of herpes simplex virus type-1
      (HSV-1) induced corneal scarring that the authors reported previously in HSV-1
      glycoprotein K (gK) vaccinated BALB/c mice challenged with HSV-1 strain McKrae
      was a general phenomenon independent of virus and mouse strains. To determine the
      gK-induced immune response leading to exacerbation of HSV-1-induced corneal
      scarring. METHODS: BALB/c or C57BL/6 mice were vaccinated with gK, ocularly
      challenged with HSV-1 strain KOS or McKrae, and the relative amount of corneal
      scarring determined 28 days after challenge. The T cells, total serum, or
      purified immunoglobulin G (IgG) isolated from gK-vaccinated mice was transferred
      individually to naive mice, and the affects on corneal scarring after HSV-1
      challenge were determined. RESULTS: The KOS challenge of gK-vaccinated BALB/c
      mice resulted in significant corneal scarring (P = 0.0003), despite the fact that
      KOS normally produces no corneal scarring. McKrae challenge of gK-vaccinated
      C57BL/6 mice resulted in significant corneal scarring (P < 0.0001), despite the
      fact that C57BL/6 mice are normally refractory to HSV-1-induced corneal scarring.
      Passive transfer of total anti-gK mouse sera or purified anti-gK mouse IgG, but
      not adoptive transfer of total anti-gK T-cells to naive mice, resulted in
      exacerbation of corneal scarring after HSV-1 challenge (P < 0.0001). Mice
      defective for T-cell-dependent antibody production were not susceptible to
      exacerbation of HSV-1-induced corneal scarring by gK vaccination (P < 0.0001).
      CONCLUSIONS: The ability of gK vaccination to exacerbate HSV-1-induced corneal
      scarring was not mouse strain or HSV-1 strain specific. The gK-induced
      exacerbation of corneal scarring was related to anti-gK IgG. How anti-gK IgG
      exacerbated HSV-1 induced corneal scarring remains to be determined.

PMID- 9152242
TI  - Hyaluronan in the human trabecular meshwork.
AB  - PURPOSE: Hyaluronan (HA) is a high-molecular weight glycosaminoglycan that can
      affect water and solute fluxes in the extracellular matrix. The distribution of
      HA in the human trabecular meshwork of nonglaucomatous eyes was examined to help
      understand the potential role of HA in the regulation of aqueous outflow
      resistance. METHODS: Histolocalization of HA was established in situ in the
      trabecular meshwork of human eyes with no known diseases of the anterior segment.
      A specific biotinylated HA-binding peptide was used as a probe for this study,
      with enhanced sensitivity of HA detection achieved by modifications of the
      fixation and staining procedures. RESULTS: Evaluation of HA staining in the
      aqueous outflow pathway in comparison to that in other ocular structures (e.g.,
      the vitreous) showed pronounced staining in the trabecular meshwork. The staining
      intensity was similar between various layers of the meshwork. Both the filtering
      and the anterior nonfiltering portions of the trabecular meshwork showed
      pronounced HA staining. The staining was localized primarily to the trabecular
      meshwork endothelial cells. CONCLUSIONS: Pronounced HA staining observed in the
      various layers of the trabecular meshwork suggests that substantial amount of HA
      is present in the nonglaucomatous outflow pathway. The staining pattern suggests
      that HA is associated with the endothelial cells lining the trabecular beams.
      This finding supports potential roles for this glycosaminoglycan in the
      regulation of the physiological aqueous outflow resistance or in the maintenance
      of the outflow channels or both. Histochemical localization of HA in the various
      layers of the non-glaucomatous meshwork provides a useful basis for future
      comparative studies of HA distribution and relative amounts in the trabecular
      meshworks of eyes affected by various types of glaucoma.

PMID- 9152243
TI  - Effects of dexamethasone on sodium-potassium-chloride cotransport in trabecular
      meshwork cells.
AB  - PURPOSE: Previous studies in the authors' laboratory have shown that bovine and
      human trabecular meshwork (TM) cells possess a robust sodium-potassium-chloride
      (Na-K-Cl) cotransport system that functions in regulating intracellular volume
      and may play a central role in modulating outflow facility across the TM.
      Dexamethasone, which can induce ocular hypertension, has been found to increase
      resistance to aqueous outflow across the TM. The current study was conducted to
      investigate the hypothesis that alteration of TM cell Na-K-Cl cotransport
      function, regulation, or both may be an underlying factor in steroid-induced
      glaucoma. To this end, the authors evaluated the effects of dexamethasone
      treatment of TM cells on Na-K-Cl cotransport activity and cotransporter protein
      expression. METHODS: Cultured bovine and human TM cell monolayers were exposed to
      dexamethasone (10(-9) to 10(-6) M) for varying times, then evaluated for Na-K-Cl
      cotransport activity or harvested for cellular membrane proteins. Cotransport
      activity was assessed as bumetanide-sensitive K influx. Cotransport protein
      expression was evaluated by Western blot analysis of cellular proteins using a
      monoclonal antibody to the human colonic T84 epithelial cell Na-K-Cl
      cotransporter. RESULTS: The authors found that 24- and 48-hour exposures of human
      and bovine TM cells to dexamethasone stimulates Na-K-Cl cotransport activity (10(
      8) to 10(-6) M dexamethasone in human cells; 10(-8) and 10(-7) M in bovine
      cells). The authors also found that dexamethasone (10(-8) M) stimulates Na-K-Cl
      cotransport activity of TM cells with exposure times as early as 12 hours and up
      to 5 days. In addition, the authors found that the level of Na-K-Cl cotransport
      protein expressed in TM cells is modulated by dexamethasone. When bovine or human
      TM cells are exposed to 10(-8) or 10(-6) M dexamethasone for 2 to 5 days,
      cotransporter protein expression is increased. With longer exposures, however,
      cotransporter protein levels decrease below control levels. Finally, the authors
      found that TM cells exposed to dexamethasone become unresponsive to regulation by
      hypertonicity and vasopressin. CONCLUSIONS: The authors' findings suggest that
      dexamethasone may be exerting its effect, at least in part, through altering Na-K
      Cl cotransport function and regulation in TM cells.

PMID- 9152244
TI  - Fine structure of the choroidal coat of the avian eye. Lymphatic vessels.
AB  - PURPOSE: To clarify the fine structure of the avian choroid and thus help explain
      the mechanisms for normal and abnormal eye function and growth. METHODS: Eyes
      from normal chickens and from experimental chickens subjected to unilateral
      paracentesis were fixed either by perfusion or in situ, with or without post
      fixation by microwave irradiation, and then processed for light and electron
      microscopic analysis. RESULTS: The avian choroid contains thin-walled lacunae,
      whose fine structure is identical to that of lymphatic vessels. The lacunae are
      much smaller toward the anterior chamber and the Schlemm's canal than posteriorly
      in the eye bulb. Large lacunae are situated primarily in the suprachoroidea, and
      their blind-ended capillary branches enter the choriocapillaris and the walls of
      large veins. The walls of the large veins contain villous structures that
      protrude into their lumina and are penetrated by thin lacunar branches and by
      side lines of the venous lumen. In normal chickens, the lacunae usually are
      devoid of blood cells. After paracentesis of the anterior eye chamber, the
      lacunae become filled with erythrocytes on the side that was operated on, but not
      on the contralateral side. CONCLUSIONS: The authors propose that the lacunae of
      the avian choroid represent a system of posterior short lymphatic vessels, which
      drain intraocular fluids directly into the eye's venous system, and that the
      villous structures are sites of communication between lacunae and veins. The
      demonstration of a choroidal lymphatic system opens new insights into the
      processes of fluid removal, control of intraocular pressure, and regulation of
      choroidal thickness in the avian eye under normal and experimental conditions.

PMID- 9152245
TI  - Gs and Gq/11 couple vasoactive intestinal peptide and cholinergic stimulation to
      lacrimal secretion.
AB  - PURPOSE: The intent of this study was to determine the physiological role of
      selected G proteins in receptor-mediated protein release by lacrimal acini.
      METHODS: The role of G proteins in lacrimal secretion was determined in tissues
      obtained from the lacrimal glands of adult male New Zealand White rabbits.
      Pertussis toxin treatment of primary acinar cultures and permeabilization of
      cultured acini with streptolysin-O and insertion of GDP beta S or antibodies
      against the alpha subunit of Gs or Gq/11 were used to determine the role of G
      proteins in vasoactive intestinal peptide (VIP) and carbachol-stimulated lacrimal
      secretion. Gs and Gq/11 were identified in lacrimal membranes obtained from
      freshly isolated lacrimal gland fragments, freshly isolated acini, and cultured
      acini by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      immunoblotting. RESULTS: Permeabilization by streptolysin-O and introduction of
      guanosine thiodiphosphate into cultured acini blocked stimulation of protein
      released by either 100 nM VIP or 100 microM carbachol by approximately 50%.
      Exposure of cultured acini to 100 ng/ml pertussis toxin for 36 to 48 hours did
      not affect stimulated release by either agonist, indicating that the guanosine
      triphosphate-dependent actions of VIP and carbachol are mediated through
      pertussis toxin-insensitive G proteins. Pertussis toxin-insensitive G proteins in
      lacrimal membranes obtained from freshly isolated glands, freshly isolated acini,
      and cultured acini were identified with polyclonal antibodies to the alpha
      subunits of Gs and Gq/11. Immunoblotting of lacrimal membranes with anti-Gs alpha
      antiserum showed two immunoreactive bands at 44 and 47 kDa. Anti-Gq/11 alpha
      antiserum detected a single band at 46 kDa in similar membrane preparations. Anti
      Gs alpha antiserum reduced the secretory response to VIP by 64% and to carbachol
      by 37%. Introduction of anti-Gq/11 alpha antiserum reduced the response to
      carbachol by 70%; however, the response to VIP was unchanged. Simultaneous
      introduction of both antisera caused no further reduction of VIP-stimulated
      release than did anti-Gs alpha antiserum alone. However, simultaneous
      introduction of both anti-Gs alpha and anti-Gq/11 alpha antisera resulted in
      complete inhibition of the effects of carbachol on protein release by cultured
      acini. CONCLUSIONS: These results show that VIP receptor activation of lacrimal
      protein release is mediated through Gs, whereas cholinergic stimulation involves
      both Gs and Gq/11. From the authors' results, the authors conclude that Gs links
      VIP receptor activation to adenylyl cyclase and cyclic adenosine 3'-5'
      monophosphate production and the ultimate release of protein by acinar cells and
      that Gq/11 links muscarinic receptor activation to phospholipase C and IP3 and
      diacylglycerol accumulation, which also leads to protein release. Furthermore, it
      is hypothesized that Gs has an additional role in the regulation of vesicular
      traffic and exocytosis.

PMID- 9152246
TI  - On the Stiles-Crawford effect with age.
AB  - PURPOSE: To determine whether the Stiles-Crawford effect remains stable after
      subjects have aged 30 years. METHODS: The relative luminous efficiency as a
      function of pupil position (Stiles-Crawford effect) was determined for the same
      seven subjects on the same apparatus in the 1960s and in 1995. The pupil opening
      was traversed nine times, at 20 degrees azimuth intervals. Data were fit with a
      revolution paraboloid yielding a peak position (x0, y0) and a peakedness (rho).
      RESULTS: Two of seven subjects showed a significant, but small, decrease in rho,
      and the other five showed, no change. No clear outcome in x0, y0 changes could be
      reported because of differences in pupil dilation then and now. CONCLUSIONS:
      Although exceptions are found on the stability of the Stiles-Crawford effect with
      age, the authors can still conclude that it is stable.

PMID- 9152247
TI  - Timolol decreases aqueous humor flow but not Na+ movement from plasma to aqueous.
AB  - PURPOSE: To determine whether the well-known effect of timolol in reducing ocular
      pressure and aqueous humor (AH) flow is a function of reduced Na+ movement from
      plasma to aqueous. Previously, the authors have shown this to be the case for
      carbonic anhydrase inhibitors. METHODS: The rate of appearance of 22Na in rabbit
      posterior aqueous was measured 1 to 3 minutes after the intravenous injection
      (time T) of the isotope. One hour before this, the animals received one of the
      following: two drops of 0.5% timolol, two drops of 3.5% pilocarpine, or 25 mg/kg
      intravenous methazolamide. At 1 minute (T + 1), a posterior chamber sample was
      taken; 2 minutes later (T + 3) a second sample was removed from the fellow eye.
      The rate constant of sodium accession is simply the difference between the two
      counts/2 minutes. Aqueous flow was measured by dilution of sulfacetamide marker
      as described previously. RESULTS: The rate constant (k(in)) for sodium entering
      the posterior chamber was 0.036 +/- 0.004 minute-1 (n = 17). Corresponding to
      previous findings, methazolamide (25 mg/kg intravenous) reduced this to 0.023 +/-
      0.003 minute-1 (n = 14). Conversely, timolol (two drops of 0.5% solution) had no
      effect on kin, which measured 0.037 +/- 0.004 minute-1 (n = 12). Similarly, as
      expected, pilocarpine had no effect on k(in) (0.035 +/- 0.003 minute-1). Control
      flow was 3.9 microliters/minute +/- 0.4; after timolol, 2.5 microliters/minute +/
      0.1; after methazolamide, 2.4 microliters/minute +/-0.2; after pilocarpine, 3.6
      microliters/minute +/- 0.2. These are converted to rate constants by dividing by
      volume of posterior aqueous (60 microliters). The control rate constant for fluid
      entry was 0.065 minute-1, 1.8-fold higher than for sodium. CONCLUSIONS: A central
      dogma of the formation of AH (and cerebrospinal fluid) is that fluid moves
      isotonically from plasma to AH or cerebrospinal fluid and, therefore, that rate
      constant k(in) for fluid and for sodium are approximately the same. In the
      authors' hands, the fluid constant was modestly higher than for sodium. This
      holds for normal function and also for the reduced k(in) for fluid and sodium
      after carbonic anhydrase inhibition. The k(in) for neither flow nor sodium was
      affected by pilocarpine. Surprisingly, however timolol, which reduces flow, had
      no effect on Na+ entry.

PMID- 9152248
TI  - Local inhibition of natural killer cell activity promotes the progressive growth
      of intraocular tumors.
AB  - PURPOSE: To study the effect of aqueous humor (AH)-mediated inhibition of natural
      killer (NK) cell activity on intraocular tumor progression. METHODS: Two NK
      sensitive tumors, RMA-S lymphoma and OCM-3 uveal melanoma, were tested in vitro
      for susceptibility to NK cell-mediated lysis in the presence or absence of AH in
      conventional cytotoxicity assays. Various numbers of RMA-S and OCM-3 tumor cells
      were injected either subcutaneously or intracamerally into C57BL/6 severe
      combined immunodeficiency mice and BALB/c nude mice respectively and tumor growth
      was monitored. The role of NK cell-mediated cytotoxicity in controlling tumor
      growth was confirmed by depleting NK cells in severe combined immunodeficiency
      mice by administering anti-asialo GM1 antibodies before subcutaneous tumor
      injection. RESULTS: AH significantly inhibited NK cell-mediated lysis of RMA-S
      and OCM-3 tumor cells in vitro and in vivo. NK sensitive RMA-S (1 x 10(4) cells)
      and OCM-3 tumors (1 x 10(6), 5 x 10(6) cells) were rejected after subcutaneous
      injection in C57BL/6 mice, whereas the same or even lower numbers of cells grew
      progressively in the eye. In vivo NK cell depletion resulted in progressive
      growth of subcutaneously injected RMA-S tumors at a dose rejected by mice with
      normal NK cell activity. CONCLUSIONS: AH inhibits NK cell activity in vitro and
      within the interior of the eye and prevents the rejection of NK-sensitive
      intraocular tumors.

PMID- 9152249
TI  - Absorption spectra of corneas in the far ultraviolet region.
AB  - PURPOSE: To study the corneal absorption in the far ultraviolet (UV) region
      between 260 and 190 nm. METHODS: Thirty-four corneal samples of thickness near 20
      microns were obtained from 18 porcine corneas and six human corneas with a
      microtome-cryostat. The authors conducted absorbance measurements of the
      sectioned corneal samples supported by two UV optical windows from 350 to 190 nm
      using a dual-beam spectrophotometer. Three whole porcine corneas were used to
      study the effect of freezing on the absorbance from 350 to near 290 nm. RESULTS:
      The absorption spectra of porcine and human corneas from 350 to 190 nm were
      measured and three segments in the spectrum between 260 and 190 nm have been
      identified. The linear absorption coefficients were determined to be 2300 +/- 330
      (cm-1) at 210 nm and 2410 +/- 370 (cm-1) at 193 nm for the porcine corneas and
      2320 +/- 470 (cm-1) at 210 nm and 2340 +/- 150 (cm-1) at 193 nm for the human
      corneas. CONCLUSIONS: A "window of ablation" in the far UV region between 220 and
      190 nm has been identified in which short laser pulses of similar durations and
      different wavelengths may be interchangeable to ablate the corneal surface with
      similar characteristics.

PMID- 9152250
TI  - Put prevention into practice.

PMID- 9152251
TI  - Obstetric liability insurance.

PMID- 9152252
TI  - Primary care research: current challenges, future needs.

PMID- 9152253
TI  - Desensitization therapy for asthma in allergic children.

PMID- 9152254
TI  - Predicting need for hospitalization in adults with asthma.

PMID- 9152256
TI  - Digoxin in heart failure.

PMID- 9152255
TI  - Oral vs i.v. steroids for asthma.

PMID- 9152257
TI  - Rapid diagnosis of acute myocardial infarction.

PMID- 9152258
TI  - Do husbands and wives agree on prostate cancer screening?

PMID- 9152259
TI  - Management of a second episode of DVT or PE.

PMID- 9152260
TI  - Individual attitudes are no match for complex systems.

PMID- 9152261
TI  - Cholesterol management and managed care.

PMID- 9152262
TI  - How important are clinician and nurse attitudes to the delivery of clinical
      preventive services?
AB  - BACKGROUND: The purpose of this study was to determine the relation between
      primary care clinic physician and nurse attitudes toward preventive services and
      the rates at which their clinics provide these services to their adult patients.
      METHODS: Forty-four private primary care clinics contracting with the sponsoring
      health maintenance organizations were recruited for a randomized controlled trial
      of an intervention consisting of training and consultation in continuous quality
      improvement and office prevention systems. Before the intervention began, 647
      clinic physicians, midlevel practitioners, and nurses in the 44 participating
      clinics completed a questionnaire addressing their attitudes toward prevention,
      and 6830 patients visiting those clinics completed a questionnaire about their
      own up-to-date preventive care status as well as clinic actions to provide eight
      important preventive services during the visit. Scales were developed from
      significantly intercorrelated sets of attitude questions. Correlations were
      calculated by clinic for the relation between mean provider scores on those
      scales and specific service rates. RESULTS: The questionnaire provided three
      scales with high internal consistency reliabilities that appear to measure
      generally favorable attitudes toward preventive services and toward improving
      them in an organized way. There was little association between these attitudes
      and rates of providing preventive services. CONCLUSIONS: While favorable
      attitudes may be helpful, they are clearly insufficient to affect the actual
      delivery of preventive services. There is reason to believe that preventive
      services rates could be improved more effectively by targeting factors related to
      the provision of preventive services, particularly those that shape the clinical
      environment in which clinicians work.

PMID- 9152263
TI  - Relative effectiveness of niacin and lovastatin for treatment of dyslipidemias in
      a health maintenance organization.
AB  - BACKGROUND: We conducted an historical cohort study to evaluate the relative
      effectiveness of niacin and lovastatin in the treatment of dyslipidemias in
      patients enrolled in a health maintenance organization (HMO). METHODS: To be
      eligible for this study, adults aged 18 years and older who were initially
      treated with either niacin or lovastatin between January 1, 1992, and December
      31, 1993, were identified from pharmacy databases. Each potentially eligible
      member with a fasting lipid panel prior to initiation of drug therapy and with a
      second fasting lipid panel between 9 and 15 months after initiation of drug
      therapy was included in the study. A total of 244 patients treated with niacin
      and 160 patients treated with lovastatin had complete data and are subjects of
      this report. RESULTS: Patients initially treated with lovastatin had higher
      baseline mean cholesterol and low-density lipoprotein (LDL) levels as well as
      higher rates of diabetes mellitus and heart disease than did patients initially
      treated with niacin. Lovastatin use was associated with a mean 25.8% decrease in
      LDL cholesterol, while niacin use was associated with a mean 17.5% drop in LDL
      cholesterol (t = 3.19, P < .002). Niacin use was associated with a 16.3%
      improvement in high-density lipoprotein (HDL) cholesterol, while HDL-cholesterol
      levels in the lovastatin group improved 1.5% (t = 4.74, P < .001). Niacin use was
      associated with an 18.4% improvement in triglycerides, while lovastatin use was
      associated with an 8% improvement in triglyceride levels (t = 2.81, P = .005).
      Differences in LDL/HDL ratio from before treatment to follow-up were no different
      in the two groups of patients (t = -1.21, P = .22). A total of 46% of patients
      initially treated with either drug reached their treatment goals in accordance
      with those set by the National Cholesterol Education Program. Drug
      discontinuation rates were 73% for niacin and 52% for lovastatin at follow-up,
      which averaged 10.7 months in each group. CONCLUSIONS: These results suggest that
      both niacin and lovastatin are effective in treating dyslipidemic patients in
      this care system, and that physicians appropriately use lovastatin more often for
      patients with higher baseline LDL levels and more comorbidity. The data also
      strongly suggest that establishing an organized, population-based approach to
      systematically identify, treat, and monitor patients with dyslipidemias may be
      the single most important intervention HMOs should consider for improving control
      of dyslipidemias on a population basis.

PMID- 9152264
TI  - Defensive testing in Dutch family practice. Is the grass greener on the other
      side of the ocean?
AB  - BACKGROUND: Ordering laboratory tests and diagnostic imaging can be part of the
      defensive behavior of the physician. How often does this occur in family practice
      in the Netherlands? Defensive behavior is defined as a clear deviation from the
      family physician's usual behavior and from what is considered to be good practice
      in order to prevent complaints or criticism by the patient or the patient's
      family. METHODS: Over a 1-year period, 1989-1990, 16 family physicians in 11
      practices with 31,343 patients recorded all episodes of care involving an order
      for laboratory tests or diagnostic imaging or both (n = 8897). The physicians
      selected one or more reasons to order each test from a fixed list of clinical
      considerations. In addition, they recorded whether they acted defensively for
      every test order. RESULTS: The participating physicians reported that some degree
      of defensive medicine was associated with 27% of all test orders. Defensive
      testing varied with the clinical reasons to order a test: the wish to exclude a
      disease or to reassure the patient was a much stronger motive for defensive
      testing than the intention to confirm a diagnosis or to screen. Defensive tests
      generally resulted in fewer abnormal findings. CONCLUSIONS: Defensive testing is
      an important phenomenon in Dutch family practice: it forms a well-defined element
      of practice despite the variations implicit in the different clinical reasons to
      order a test. Defensive testing is associated with a lower probability of finding
      an abnormal test result. The analysis of family physicians' clinical reasons for
      ordering tests becomes more meaningful when defensive testing is included.

PMID- 9152266
TI  - Injuries involving off-road cycling.
AB  - BACKGROUND: Data on injuries due to off-road bicycling are scarce, but do
      indicate that injuries in this sport are frequent. We examined the pattern of
      injuries to off-road riders as part of a larger study of bicycle injuries and
      helmet use. METHODS: We undertook a prospective study of bicycle-related injuries
      identified at seven emergency departments in Seattle, Washington, between March
      1992 and August 1994. Hospitalized patients and medical examiners' cases were
      included. Detailed questionnaires and abstraction of all medical records provided
      information on crash and rider characteristics and injury type and severity.
      RESULTS: A total of 3390 injured riders participated, representing an 88%
      response rate. Of all injured cyclists, 127 (3.7%) were injured riding "off
      road." Seventy-three percent of off-road cyclists were 20 to 39 years of age, and
      86.6% were male. Helmet use was 80.3% for off-road cyclists as compared with
      49.5% for other cyclists. The number of head and face injuries for the off-road
      cyclists was only 40% of the number incurred by other cyclists. Four percent of
      off-road cyclists had severe injuries (injury Severity Score > 8), and 6.3% were
      hospitalized, compared with 6.8% and 9.4%, respectively, of other cyclists.
      CONCLUSIONS: The majority of off-road bicycling injuries are minor. Off-road
      cyclists are less likely to have head and face injuries than other cyclists and
      are more likely to wear helmets.

PMID- 9152265
TI  - Colonoscopy performed by a family physician. A case series of 751 procedures.
AB  - BACKGROUND: Colonoscopy, including biopsy and polypectomy, is a procedure not
      commonly performed by primary care physicians. The purpose of this research was
      to present a large case series of colonoscopic procedures performed by a family
      physician in a rural practice. METHODS: A chart review of every colonoscopy
      procedure performed by a family physician over a 7-year period determined the
      demographic characteristics, indications, findings, and complications for each
      procedure. RESULTS: A total of 751 colonoscopies were performed on 555 patients
      (347 women and 208 men), with a mean age of 53.8 years. In 91.5% of procedures,
      the cecum was intubated. The most common indications for colonoscopy were
      bleeding (49.9%), polyp follow-up (20.9%) abdominal pain (11.7%), diarrhea
      (11.6%), and abnormal findings on flexible sigmoidoscopy (8.4%). Three hundred
      sixteen benign polyps were discovered and removed by either biopsy or
      polypectomy. There were 184 adenomatous colorectal polyps found in 134 (17.8%)
      colonoscopies. Of these 184 adenomatous polyps, 106 (58%) were potentially within
      reach of the flexible sigmoidoscope. Only three adenocarcinomas were discovered
      during the entire study period. There was only one major procedural complication:
      a patient experienced blood oozing from a polypectomy stump; cautery stopped the
      bleeding, and the patient was hospitalized overnight, with no further
      intervention or transfusion required. There were five other self-limited
      complications, including adverse reactions to sedation and infiltration at the
      intravenous site. CONCLUSIONS: Colonoscopy with polypectomy that was safely and
      competently performed in a solo rural practice adds to the evidence that
      experienced family physicians can provide this important service to their
      community.

PMID- 9152267
TI  - Primary care of adults with mental retardation.
AB  - BACKGROUND: There is a national trend to deinstitutionalize mentally retarded
      adults, placing them in community residential settings. As a result, community
      based primary care physicians will assume responsibility for their medical care.
      Primary care physicians may have uncertainties regarding the medical care of this
      population. The purpose of this case series is to describe the medical care of a
      group of adults with mental retardation during their first year of community
      residence following deinstitutionalization, and to provide practical advice to
      family physicians who care for these adults. METHODS: Medical diagnoses and
      medications at the time of deinstitutionalization of a series of 21 adults were
      abstracted from institutional records and transfer forms. Follow-up data were
      obtained from office medical records. RESULTS: In the first year following
      deinstitutionalization, each patient averaged 6.6 office visits to a family
      physician. Newly identified major health impairments were: chronic persistent
      hepatitis due to hepatitis B, acid peptic disease, gastroesophageal reflux
      disease, dysphagia, primary degenerative dementia, absence seizures,
      bronchiectasis, and idiopathic iridocyclitis. Significant changes in
      pharmacotherapy included consolidation of multidrug anticonvulsant regimens and
      discontinuance of psychotropics and laxatives. Health maintenance practices
      included hepatitis B immunizations, cholesterol determinations, smoking cessation
      counseling, and calcium supplementation. CONCLUSIONS: Newly deinstitutionalized
      patients require careful diagnostic and therapeutic reassessment. Family
      physicians assuming their care need to look for conditions common in this
      population, including dysphagia, seizure disorders, chronic hepatitis B, and
      sensory impairments. Previously neglected health maintenance practices need to be
      instituted. Pharmacotherapies, particularly anticonvulsants, psychotropics, and
      laxatives, may be amenable to dosage reduction or discontinuance.

PMID- 9152268
TI  - Methylphenidate in the treatment of coma.
AB  - While there is significant morbidity and mortality involving patients in
      semicomatose and comatose states, the care of such patients has traditionally
      been limited to supportive measures. We report two cases of patients treated with
      methylphenidate hydrochloride: the first, a patient in a semicomatose state
      resulting from traumatic brain injury, and the second, a patient in a comatose
      state secondary to a subdural hematoma that occurred after a fall. Treatment with
      methylphenidate may provide neurostimulations by augmenting the activity of
      injured neuronal tissue within the reticular activating system, and by amplifying
      the net effect of the reduced number of viable neurons. Methylphenidate is a low
      cost, potentially efficacious intervention for reducing the duration of comas,
      for preventing life-threatening and costly complications of prolonged
      unconsciousness, and for promoting early ambulation and recovery. Further
      research using more rigorous research designs to ascertain the effectiveness of
      methylphenidate in the treatment of patients in semicomatose and comatose states
      is needed.

PMID- 9152269
TI  - Treatment of penicillin-resistant pneumococcus with penicillin: a case report.
AB  - Antibiotic resistance of Streptococcus pneumoniae is on the rise in many parts of
      the world, and varies widely across the United States. This is of growing concern
      as organisms become resistant to cephalosporins and macrolides as well as to beta
      lactam antibiotics. Susceptibility testing has become a critical element in
      antibiotic selection. In vitro susceptibility, however, may not correlate with
      clinical susceptibility. For example, penicillin G in appropriate doses is often
      effective therapy for drug-resistant Streptococcus pneumoniae pneumonia. This
      report takes into account in vitro susceptibility as well as the patient's
      coexisting morbidities in the treatment of penicillin-resistant S pneumoniae with
      penicillin G.

PMID- 9152270
TI  - Common sense.

PMID- 9152271
TI  - Otoacoustic emissions as a screening tool for sensorineural hearing loss.

PMID- 9152272
TI  - A gift of life: umbilical cord blood.

PMID- 9152273
TI  - Should children with hemoglobinopathies be offered unrelated-donor cord blood
      stem cell transplantation?

PMID- 9152274
TI  - Heart rate variability: a new physiologic marker of autonomic neurotoxicity.

PMID- 9152275
TI  - The febrile child with sickle cell disease: a pediatrician's quandary.

PMID- 9152276
TI  - Umbilical cord blood stem cells: application for the treatment of patients with
      hemoglobinopathies.
AB  - Even though there is recognized morbidity and death associated with bone marrow
      transplantation, this procedure has been performed successfully in a substantial
      number of patients with hemoglobinopathies. However, finding a suitable related
      donor is often difficult and the morbidity associated with the use of unrelated
      donors is high. Several reports indicate that fewer than 30% of patients with
      thalassemia major and fewer than 20% of patients with sickle cell anemia have
      histocompatible siblings. Human umbilical cord blood (UCB) contains hematopoietic
      stem cells capable of reconstituting bone marrow. To date, approximately 200
      transplantations have been performed with UCBs. Early results suggest that, even
      with substantial human leukocyte antigen (HLA) incompatibility, a decrease in the
      incidence of graft-versus-host disease occurs with cord blood. The extent to
      which HLA incompatibility can be tolerated when cord blood is used has not been
      determined. These results raise the possibility that UCB obtained from unrelated
      donors could be used for transplantation in patients with hemoglobinopathies.
      This review summarizes current data on UCB stem cells used for transplantation in
      hematologic diseases. The review contains a discussion of the potential uses of
      UCB for patients with hemoglobinopathies and the value of programs designed to
      collect UCB from newborn infants with hemoglobinopathies, from siblings of
      patients with hemoglobinopathies, and from groups of ethnic minorities similar to
      those in which hemoglobinopathies are found.

PMID- 9152277
TI  - Comparison between observation of spontaneous movements and neurologic
      examination in preterm infants.
AB  - OBJECTIVE: The Prechtl method of qualitative assessment of general movements
      (GMs) has been shown to be a good predictor of neurologic outcome in fetuses,
      preterm infants, and term infants. The aim of this study was to compare the
      results of this new technique with those of traditional neurologic examination
      and of cranial ultrasonography in preterm infants. METHODS: Serial videotape
      recordings (with off-line assessment of GMs), ultrasound examination of the
      brain, and neurologic examinations were performed from birth until about 6 months
      of corrected age, on a group of 66 preterm infants whose gestational age ranged
      from 26 to 36 weeks (mean 30.7 weeks). The agreement between the two techniques
      and their predictive power, with respect to the neurologic outcome at 2 years of
      corrected age, were evaluated for five different age groups from preterm age to
      65 weeks of postmenstrual age. RESULTS: Overall agreement of the neurologic and
      GM findings was 80.3% and strongly age related (lower during the preterm and term
      periods and higher thereafter). At all ages the results of GM observation
      correlated highly with neurologic outcome; they showed higher sensitivity and
      specificity than the neurologic examination. This held true in particular before
      term age, when poor neurologic responses might be related to transient
      complications, and at term age, mainly because of infants with normal neurologic
      examination results but unfavorable outcome. During the preterm period the
      ultrasound results showed a better specificity and a lower sensitivity to outcome
      than GM findings. CONCLUSIONS: The results of this study indicate that quality
      assessment of GMs should be added to traditional neurologic assessment,
      neuroimaging, and other tests of preterm infants for diagnostic and prognostic
      purposes.

PMID- 9152278
TI  - Hearing impairment in infants after meningitis: detection by transient evoked
      otoacoustic emissions.
AB  - OBJECTIVE: To evaluate the feasibility and cost-effectiveness of using transient
      evoked otoacoustic emissions (TEOEs) to assess hearing in infants recovered from
      meningitis. METHODS: Recordings of TEOEs and visual reinforcement audiometry
      (VRA) were performed in a prospective study of 39 children aged 6 to 24 months
      recovering from a purulent meningitis. Patients with no TEOEs, or whose VRA
      findings were abnormal, were also tested by impedance audiometry and recording of
      auditory brain-stem responses (ABRs) after treatment of any secretory otitis
      media. Costs were compared with those of a previous protocol including VRA,
      impedance audiometry, and ABR for all children. RESULTS: A total of 29 children
      had TEOEs in both ears and normal VRA findings. Ten children lacked TEOEs in one
      or both ears; 9 of them had otitis media with effusion. Further examination by
      VRA and ABR led to the diagnosis of bilateral sensorineural hearing loss in 2.6%
      (1/39) of patients and unilateral sensorineural hearing loss in 7.7% (3/39) of
      patients. Cost analysis revealed that this protocol costs about half the previous
      one. CONCLUSION: Recording TEOEs appears to be a feasible and cost-effective
      hearing screening test for infants recovered from meningitis. If TEOEs are
      absent, impedance audiometry, ABR recordings, and audiometric evaluation
      techniques are needed to distinguish between conductive and sensorineural hearing
      loss and to assess hearing thresholds precisely.

PMID- 9152279
TI  - Alterations in cord blood leukocyte subsets of patients with severe hemolytic
      disease after intrauterine transfusion therapy.
AB  - OBJECTIVES: The aim of this study was to compare, at delivery, the cord blood
      mononuclear cells of infants with severe hemolytic disease who received
      intrauterine transfusion (IUT) therapy with the cord blood mononuclear cells of
      healthy nonimmunized control neonates. STUDY DESIGN: The expression of leukocyte
      markers on CBMNC of 14 IUT-treated and 18 control neonates was analyzed by means
      of a panel of well-defined monoclonal antibodies and flow cytometry. RESULTS:
      Patients with severe hemolytic disease requiring IUT treatment displayed
      significant altered expression of some leukocyte markers when compared with
      control subjects. The circulating CD34+ progenitor cells were significantly
      increased in comparison with cord blood of nonimmunized neonates. IUT-treated
      patients also showed a statistically significant decrease in natural killer (NK)
      cell associated markers (CD16, CD57, and CD69), which correlated with a lower
      expression of CD56. In these patients an increased expression of CD3/CD45RO and
      CD3/CD5 was also noted. Although these latter alterations were statistically
      significant in a single-parameter analysis, the significance disappeared after
      multi-parameter analysis because of a loss of statistical power. CONCLUSIONS:
      Compared with nonimmunized healthy newborn infants, patients who underwent IUT
      also exhibited a down-regulation of NK cells and NK cell associated markers, as
      well as increased numbers of CD34+ progenitor cells.

PMID- 9152280
TI  - Analysis of heart rate variability demonstrates effects of development on vagal
      modulation of heart rate in healthy children.
AB  - OBJECTIVES: Analysis of heart rate variability (HRV) has been found to be a
      useful method of assessing cardiovascular autonomic control, but normal values
      for standard HRV measures in children have not been established. We analyzed HRV
      in 60 healthy children aged 3 to 15 years to determine normal values and to
      assess the effects of development on cardiac autonomic control with the use of
      ambulatory electrocardiographic monitoring. RESULTS: The high-frequency (HF)
      component, an index of cardiac autonomic tone, increased significantly with age
      from 3 to 6 years (p < 0.01) and decreased with age from 6 to 15 years (p <
      0.01), and the magnitude of HF correlated significantly with the R-R intervals.
      Thus the changes in cardiac autonomic tone could be described as a simple
      equation using age and heart rate. CONCLUSIONS: We present normal values and
      changes in the cardiac autonomic system during childhood after HRV analysis,
      which could lead to a better understanding and treatment of cardiac disease in
      children.

PMID- 9152281
TI  - Detection of maternofetal transfusion by placental alkaline phosphatase levels.
AB  - We investigated the volume of maternofetal transfusion by measuring placental
      alkaline phosphatase (PLAP) as an indicator of placental passage. PLAP levels
      were measured in 135 pairs of maternal-neonatal sera. Estimated volumes of
      maternofetal transfusion were calculated with the following formula: Volume of
      transfusion (in milliliters) = 85 ml/kg x BW (in kilograms) x (PLAPAB-PLAP1MO)/
      PLAPMA, where BW is the birth weight, PLAPAB is the PLAP level in neonatal serum
      at birth, PLAP1MO is the PLAP level in neonatal serum at 1 month of age, and
      PLAPMA is the PLAP level in maternal serum at delivery. The mean PLAPMA, PLAPAB,
      and PLAP1MO levels were 276.95 +/- 159.74 IU/L, 3.83 +/- 2.17 IU/L, and 0.25 +/-
      0.22 IU/L, respectively. The mean volume of maternofetal transfusion was
      estimated to be 3.33 +/- 1.68 ml. The mean estimated volume of maternofetal
      transfusion per kilogram of birth weight was significantly lower in cases of
      scheduled cesarean delivery (0.74 +/- 0.35 ml/kg) than in cases of vaginal
      delivery (1.18 +/- 0.54 ml/kg; p < 0.001) and emergency cesarean delivery (1.73
      +/- 1.00 ml/kg; p < 0.01). In scheduled cesarean delivery a significant positive
      correlation between gestational age and the estimated volumes of transfusion per
      kilogram of birth weight was observed. In cases of vaginal delivery, the
      estimated volume of transfusion per kilogram of birth weight was significantly
      lower in the group with short labor (< 5 hours: 0.92 +/- 0.32 ml/kg) than in the
      group with prolonged labor (> or = 5 hours: 1.29 +/- 0.61 ml/kg; p < 0.001). PLAP
      was considered to be useful for estimating the volume of maternofetal
      transfusion. The transfer volume appeared to relate to uterine contractions and
      to histologic changes in the placenta with aging.

PMID- 9152282
TI  - Thirst and vasopressin secretion counteract dehydration in newborn infants.
AB  - OBJECTIVE AND STUDY DESIGN: Our goal was to study the water balance in healthy
      breast-fed infants (n = 139) during their first 5 days, by cross-sectional
      measurements of body weight, serum sodium, serum osmolality, and hematocrit. We
      also investigated infants' capacity to conserve body water by increased secretion
      of vasopressin, the main antidiuretic hormone in human beings. RESULTS: The
      maximal body weight reduction was 5.7% +/- 1.7% (mean +/- SD) of birth weight and
      most infants started to gain weight when they were 3 days old. The serum sodium
      level at 16 +/- 4 hours (on day of birth) was 142 mmol/L; the level increased
      after 1 day (p < 0.01) and remained constantly high for the following 2 days (p <
      0.05). The serum osmolality was increased at 1 day (p < 0.01) and 2 days (p <
      0.05) compared with the value on the day of birth (296 mOsm/kg). The plasma
      vasopressin level was constant up to 24 hours (1 day), but decreased during the
      next 2 days (p < 0.01). Infants with body weight reduction exceeding 10% (n = 15)
      had a further elevation of the serum sodium level (p < 0.0001) and serum
      osmolality (p < 0.0001), and the plasma vasopressin level was twofold higher (p <
      0.0001) compared with corresponding levels in infants with less weight reduction.
      These infants also had a reduced interval between two subsequent feedings (p <
      0.001). The hematocrit remained unchanged irrespective of the degree of weight
      reduction. CONCLUSIONS: When the reduction of body weight exceeds 10%, the
      newborn infant releases vasopressin in response to fluid hypertonicity. This
      state also affects feeding behavior, perhaps as an expression of thirst. It is
      likely that hormone release is also stimulated in parallel with a weight
      reduction of less than 10%, because it is also accompanied by a hyperosmotic
      state.

PMID- 9152283
TI  - Mechanics and energetics of nutritive sucking: a functional comparison of
      commercially available nipples.
AB  - The purpose of this study was to compare the mechanics of sucking for 48 term
      infants with four different nipple units: Gerber Newborn (Gerber Products
      Company, Fremont, Mich.), Playtex (Playtex Products, Westport, Conn.), Evenflo
      (Evenflo Products Co., Canton, Ga.), and Gerber NUK. At 24 hours after birth,
      infants were assigned randomly to one of the nipple units and were studied twice
      with that nipple unit. A customized data acquisition system was used to measure
      and record the following variables: intraoral suction, sucking frequency, work,
      power, milk flow, milk volume per suck, and oxygen saturation. Although no
      statistically significant differences among the nipple units were noted for
      intraoral suction, sucking frequency, power, and oxygen saturation, the data
      revealed that the Playtex nipple unit was accompanied by higher peak milk flow
      and greater volume of milk per suck (p < 0.05). Infants fed differently with the
      Playtex nipple than they did with the other nipples. Our findings indicate that
      the Playtex nipple permits a greater milk flow in response to similar amounts of
      suction, work, and power when compared with others. The mean total work per such
      was significantly lower in the Gerber NUK group compared with the Playtex group.
      In addition, the total number of sucks per volume ingested was higher, and the
      total time to ingest a specific quantity of milk was longer for the Gerber NUK
      nipple.

PMID- 9152284
TI  - Apnea after immunization of preterm infants.
AB  - OBJECTIVE: To determine the frequency of adverse reactions, particularly the
      occurrence of apnea, among preterm infants after immunization with diphtheria and
      tetanus toxoids and whole cell pertussis vaccine adsorbed (DTP) and Haemophilus
      influenzae type b conjugate (HibC) vaccine in the neonatal intensive care unit.
      STUDY DESIGN: After the occurrence of apnea in two preterm infants following
      immunization with DTP and HibC, a prospective surveillance of 97 preterm infants
      younger than 37 weeks of gestation who were immunized with DTP (94 also received
      HibC at the same time) in the neonatal intensive care unit was performed to
      assess the frequency of adverse reactions and in particular, the occurrence of
      apnea. For each infant, data were recorded for a 3-day period before and after
      receipt of the immunization. RESULTS: The majority of preterm infants tolerated
      immunizations with DTP and HibC without ill effects. However, 12 (12%) infants
      experienced a recurrence of apnea, and 11 (11%) had at least a 50% increase in
      the number of apneic and bradycardic episodes in the 72 hours after immunization.
      This occurred primarily among smaller preterm infants who were immunized at a
      lower weight (p = 0.01), had experienced more severe apnea of prematurity (p =
      0.01), and had chronic lung disease (p = 0.03). CONCLUSION: The temporal
      association observed between immunization of preterm infants and a transient
      increase or recurrence of apnea after vaccination merits further study.
      Cardiorespiratory monitoring of these infants after immunization may be
      advisable.

PMID- 9152285
TI  - The hospital cost of congenital syphilis.
AB  - OBJECTIVE: To determine the hospital cost of caring for newborn infants with
      congenital syphilis. STUDY POPULATION: All live-born singleton neonates with
      birth weight greater than 500 gm at an inner-city municipal hospital in New York
      City in 1989. METHODS: We compared the characteristics of 114 infants with case
      compatible congenital syphilis with those of 2906 infants without syphilis. Cost
      estimates were based on New York State newborn diagnosis-related groups (DRG)
      reimbursements adjusted for length of stay, birth weight, preterm delivery, and
      selected maternal risk factors, including infection with the human
      immunodeficiency virus, cocaine use during pregnancy, and history of injected
      drug use. RESULTS: For infants with congenital syphilis, the unadjusted mean cost
      ($11,031) and the median cost ($4961) were more than three times larger than
      those for infants without syphilis (p < 0.01). After adjustment, congenital
      syphilis was associated with an additional length of hospitalization of 7 1/2
      days and an additional cost of $4690 (both p < 0.01) above mean study population
      values (7.13 days, $3473). CONCLUSIONS: Based on the number of reported cases
      (1991 to 1994), the average annual national cost of treating infants with
      congenital syphilis is approximately $18.4 million (1995 dollars). This estimate
      provides a benchmark to assess the cost-effectiveness of strategies to prevent,
      diagnose, and treat the disease.

PMID- 9152286
TI  - Community impact of childhood varicella infections.
AB  - OBJECTIVES: To assess age-specific incidence rates, health care utilization, and
      lost parental work associated with varicella infection in a population-based
      cohort of children, and to validate parent-reported health care utilization data.
      STUDY DESIGN: We conducted a telephone survey of a population-based cohort of
      4557 households with children aged birth to 13 years. Medical chart abstraction
      was used to validate health care utilization information. RESULTS: We report
      varicella incidence rates in preschool children that are 2 to 2.5 times higher
      than previous studies. Rates of varicella-related serious complications,
      hospitalizations, parental work leave, and medication use are comparable with
      rates reported elsewhere. However, health provider visits occurred only 0.3 to
      0.5 times as frequently as estimated in other studies. One hundred percent of
      reported hospitalizations and serious complications and 92% of provider visits
      were validated to be within the study time frame through medical chart audits.
      CONCLUSIONS: Parents are an accurate source of varicella-related health care
      utilization data. Parent-reported incidence data indicate that varicella
      infections are increasing in preschool children. This shift to infections in
      younger children may be related to the increased use of out-of-home care for
      infants and young children. Furthermore, the shift may after the community burden
      of varicella because of the observed increased parental work loss and decreased
      frequency of health care visits in the preschool children.

PMID- 9152287
TI  - Endoscopy of the upper gastrointestinal tract as a diagnostic tool for children
      with human immunodeficiency virus infection.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence of upper
      gastrointestinal tract lesions in children with human immunodeficiency virus
      (HIV) infection who undergo endoscopy of the upper gastrointestinal tract and to
      identify important clinical predictors of abnormal endoscopic results. METHODS:
      All HIV-infected children who underwent endoscopy and were followed at Children's
      Hospital, Boston, from January 1985 to August 1994 were studied. The main outcome
      measure was endoscopic results, which were categorized into observational,
      histologic, and microbiologic findings. Potential predictors included height,
      weight, nutritional interventions, HIV disease stage, CD4 T-lymphocyte count,
      medications, active infections, and indications for endoscopy. RESULTS: Forty
      three endoscopies in unique patients are reported. Most children had advanced HIV
      infection (67% acquired immunodeficiency syndrome, mean CD4 T-lymphocyte count z
      score = -2.71, weight z score = -2.04). An abnormal endoscopic finding was
      discovered in 93% of children and confirmed by histologic, microbiologic, or a
      combination of these studies in 72% of children. Thirty-five percent of children
      had an opportunistic pathogen identified endoscopically; 65% of these pathogens
      were previously undiagnosed. Observational findings often were poor indicators of
      histologic and microbiologic abnormalities. Independent predictors of abnormal
      histologic findings include younger age at endoscopy (odds ratio (OR) = 1.16 per
      year, 95% confidence interval (CI) (1.02, 1.33)) and guaiac-negative stools (OR =
      16.7, 95% CI (1.92, 142.9)). Independent predictors of finding a pathogen at the
      time of endoscopy include a greater number of indications for endoscopy (OR = 2.6
      per indication, 95% CI (1.3, 5.3)) and diagnosis of acquired immunodeficiency
      syndrome (OR = 16.4, 95% CI (1.3, 213)). No other gastrointestinal, nutritional,
      or immunologic parameters were significantly predictive of endoscopic outcomes.
      Medical management was changed in 70% of children because of the endoscopic
      findings. CONCLUSIONS: Endoscopy is a useful tool to direct therapy against
      peptic and infectious disorders of the upper gastrointestinal tract in children
      with HIV infection. Specific gastrointestinal symptoms are not useful predictors
      of abnormal results.

PMID- 9152288
TI  - Epidemiologic study of Langerhans cell histiocytosis in children.
AB  - OBJECTIVE: The etiology and pathogenesis of Langerhans cell histiocytosis (LCH)
      remain poorly understood. We conducted an exploratory epidemiologic study to
      investigate potential risk factors associated with LCH. STUDY DESIGN: We used a
      case-control study design to obtain data from parents of children with LCH (n =
      459) who were members of the Histiocytosis Association of America and Canada. The
      two control groups consisted of 683 community control subjects and 3719 children
      with childhood cancers treated at participating Children's Cancer Group
      institutions. RESULTS: The median age at diagnosis of LCH was 1.8 years (range
      0.1 to 14.6 years). Cases were categorized as multisystem LCH (MS-LCH) (n = 208)
      and single-system LCH (SS-LCH) (n = 198). Statistically significant associations
      included the following: infections in the neonatal period (MS-LCH, odds ratio
      (OR) = 2.2), solvent exposure (SS-LCH, OR = 54.9), childhood vaccinations (MS-LCH
      and SS-LCH, OR = 0.4), thyroid disease in the proband (MS-LCH and SS-LCH, OR =
      21.6), and family history of thyroid disease (MS-LCH and SS-LCH, OR = 1.4). The
      association with thyroid disease in the proband was explained partially by the
      involvement of the pituitary, with the relative risk decreasing when patients
      with diabetes insipidus and thyroid involvement were excluded from analysis.
      CONCLUSIONS: This large hypothesis-generating study provides directions for
      future investigations in well-designed population-based or hospital-based
      epidemiologic studies.

PMID- 9152289
TI  - Contribution of growth hormone deficiency to the growth failure that follows bone
      marrow transplantation.
AB  - Conditioning for bone marrow transplantation (BMT) by total body irradiation
      frequently causes growth failure. The contribution of growth hormone (GH)
      deficiency to this failure was assessed in 38 patients given three types of body
      irradiation: group 1 (n = 18) was given 12 Gy total body irradiation as six
      fractions, group 2 (n = 14) 10 Gy (one dose) total body irradiation, and group 3
      (n = 6) 6 Gy (one dose) thoracoabdominal irradiation, which did not involve the
      hypothalamic-pituitary area. At the first evaluation, 2.9 +/- 0.2 (SE) years
      after BMT, the values for the plasma insulin-like growth factor I (IGF-I) and its
      GH-dependent binding protein (IGFBP-3) were similar in groups 1 and 2 but
      significantly greater in group 3 (p < 0.02 for IGF-I and 0.01 for IGFBP-3). These
      values were similar in those patients in groups 1 and 2 who had low GH peaks
      after stimulation (12 patients: IGF-I, 0.8 +/- 0.2 U/ml; IGFBP-3, 1.6 +/- 0.2
      mg/L) and in those with normal GH peaks (20 patients: 1 +/- 0.1 U/ml and 1.8 +/-
      0.1 mg/L). The decrease in height 2 years after BMT was significantly (p < 0.01)
      greater in group 2 than in groups 1 and 3, but 5 years after BMT it was similar
      in groups 1 and 2 (0.9 +/- 0.2 and 1.4 +/- 0.3 SD), significantly (p < 0.05)
      greater in group 2 than in group 3 (0.7 +/- 0.2 SD). The individual height
      changes between BMT and the last clinical evaluation before GH therapy were not
      correlated with the age at BMT, GH peak after stimulation, plasma IGF-I
      concentration, or IGFBP-3 concentration. Seven patients with GH deficiency were
      given GH therapy; their growth rate became normal for age (-2.1 +/- 0.9 SDS
      before and -0.2 +/- 0.4 SDS for the first year; not significant) without any
      catch-up growth. We conclude that plasma IGF-I and IGFBP-3 values are of no
      diagnostic value for GH deficiency after TBI. Their normal or high levels,
      despite low GH peaks, suggest that bone irradiation induces lesions causing
      resistance to IGF-I.

PMID- 9152290
TI  - Efficacy and safety of one year of growth hormone therapy in steroid-dependent
      nephrotic syndrome.
AB  - OBJECTIVES: To study the efficacy and safety of 1 year of growth hormone (GH)
      therapy in children with steroid-dependent nephrotic syndrome. STUDY DESIGN: A
      prospective pilot, open study in which GH (mean dose 0.32 mg/kg per week) was
      administered for 1 year to 8 children with steroid-dependent nephrotic syndrome
      requiring prednisolone (mean dose 0.46 mg/kg per day) to maintain remission.
      Steroid dependence was defined as recurrence of proteinuria within 2 weeks of
      discontinuation of prednisolone, or when the dose was lowered below a critical
      level. At entry, all patients had been steroid dependent for at least 1 year.
      Anthropometric and bone mineral density measurements after treatment were
      compared with 1-year pretreatment data. RESULTS: Pretreatment mean (+/-SD)
      chronologic age was 12.6 (+/-3.1) years, with a mean bone age of 9.1 (+/-2.0)
      years, with delayed puberty in five patients. The mean height velocity increased
      from 3.7 (+/-1.4) to 9.4 (+/-2.1) cm/yr after 1 year of treatment (p < 0.05). The
      mean height standard deviation score increased from -1.4 (+/-1.6) to -0.3 (+/
      1.1), (p < 0.05). In the spine, the mean bone mineral density increased from 0.50
      to 0.64 gm/cm2 (p < 0.05), and in the femoral neck, from 0.55 to 0.64 gm/cm2 (p <
      0.05) after 1 year of treatment. Mean lean body mass increased from 58.1% to
      62.6% (p < 0.01). There were no significant changes in creatinine clearance,
      fasting glucose, fasting insulin, or glycosylated hemoglobin levels. The mean
      bone age increased to 11.4 (+/-2.4) years, and pubertal stage advanced in 2
      patients. CONCLUSIONS: One year of GH therapy is effective in improving the
      height standard deviation score, height velocity, bone mineral density, and lean
      body mass of children with steroid-dependent nephrotic syndrome. There were no
      significant adverse effects. However, the bone age accelerated at a greater pace
      than the height age, and further studies are required to define the role of GH
      therapy in steroid-dependent nephrotic syndrome.

PMID- 9152291
TI  - Down-regulation of manganese-superoxide dismutase gene expression in idiopathic
      nephrotic syndrome.
AB  - An oxidant stress has been shown to prevail in experimental and clinical
      nephrotic syndrome. Such oxidant stress may be induced by a reduced activity of
      antioxidant systems. We examined the altered expression of manganese-superoxide
      dismutase (Mn-SOD), an antioxidant enzyme, in patients with idiopathic nephrotic
      syndrome, in whom an increased oxidant stress had been demonstrated. The Mn-SOD
      activities in peripheral blood mononuclear cells obtained from 12 patients with
      active nephrotic syndrome (6.0 +/- 1.1 years of age, mean +/- SE) and
      hypoproteinemia were 42% lower (p < 0.05) than in 12 control subjects (5.5 +/-
      0.5 years of age) with normal serum total protein concentrations. Reverse
      transcriptase polymerase chain reaction also demonstrated that Mn-SOD messenger
      RNA expression in the patients with nephrotic syndrome was, on average, 59% lower
      than in control subjects. Because expressions of some genes are sensitive to
      serum, the serum dependency of Mn-SOD gene transcription was studied in
      glomerular endothelial cells transfected with a luciferase reporter gene fused
      with a rat Mn-SOD DNA fragment of -806 to +22 bp of the transcription initiation
      site (-806:+22). When these cells were exposed to different concentrations of
      fetal bovine serum (0.5% to 15%), the transcriptional activities determined by
      luciferase activities were proportional to serum concentrations. This serum
      dependent transcriptional activation was also demonstrated by the fragment (
      220:+22) but not by the fragment (-220:-20). When glomerular endothelial cells
      transfected with the fragment (-220:+22) were treated with 5% serum from patients
      with active nephrotic syndrome, transcriptional activation was more than 80% less
      than that by 5% serum from control subjects without nephrosis. These results
      indicate that Mn-SOD gene transcription is regulated at least in part by serum,
      and that the serum-dependent transcription of the gene is diminished in patients
      with idiopathic nephrotic syndrome. The regulatory region of serum-dependent gene
      transcription resides within its early promoter region. Our findings suggest that
      down-regulation of antioxidant enzyme transcription may contribute increased
      oxidant stress in idiopathic nephrotic syndrome.

PMID- 9152292
TI  - Comparison of skin stapling devices and standard sutures for pediatric scalp
      lacerations: a randomized study of cost and time benefits.
AB  - OBJECTIVE: To compare the total costs and the physician time requirements for
      suture and staple repair of pediatric scalp lacerations. STUDY DESIGN: Eighty
      eight children, 13 months to 16 years of age, coming to a children's hospital
      emergency department with simple scalp lacerations were prospectively randomly
      selected to receive staple or suture repair. Wound lengths, times required for
      initial wound care and closure, and equipment use were recorded. Patients
      returned in 1 week for suture or staple removal and wound reevaluation. The two
      methods were compared in terms of both time expended and costs of equipment and
      physician compensation. RESULTS: Forty-five children underwent staple repair and
      43 underwent suture repair. There were no differences in age, sex, wound length,
      number of sutures or staples per centimeter, or physician experience. Stapling
      resulted in shorter wound closure times (65 vs 397 seconds; p < 0.0001) and
      shorter overall times for wound care and closure (395 vs 752 seconds; p <
      0.0001). Staple repair was less expensive in terms of equipment ($12.55 vs
      $17.59; p < 0.0001) and total cost based on equipment and physician time ($23.55
      vs $38.51; p < 0.0001). The follow-up rate was 91%, with no cosmetic or
      infectious complications in either group. CONCLUSIONS: Stapling is faster and
      less expensive than suturing in the repair of uncomplicated pediatric scalp
      lacerations, with no additional complications. Physicians who treat children with
      scalp lacerations should consider the use of stapling devices.

PMID- 9152293
TI  - Recurrent Streptococcus pneumoniae sepsis in children with sickle cell disease.
AB  - Streptococcus pneumoniae sepsis is the most common invasive infection among
      patients with sickle cell disease. The risk of a recurrent episode of sepsis and
      subsequent death in those patients who have had a previous septic event is much
      higher. Patients with sickle disease who have had pneumococcal sepsis should
      continue penicillin prophylaxis indefinitely and should not be candidates for out
      patient management of febrile episodes.

PMID- 9152294
TI  - Neonatal and delayed-onset liver involvement in disorders of oxidative
      phosphorylation.
AB  - Inborn errors of oxidative phosphorylation have been recognized as possible
      causes of hepatic failure in the neonate, and respiratory enzyme deficiencies
      have been described in the liver of affected individuals. On the basis of a
      series of 22 cases, we describe respiratory enzyme deficiency as a cause of early
      onset fatal hepatic failure with frequent neurologic involvement. In addition, we
      have identified a delayed-onset form of hepatic failure with a milder clinical
      course and inconstant neurologic involvement. Thus we suggest that genetic
      defects of oxidative phosphorylation be considered as a cause of liver
      dysfunction in infancy, regardless of the severity of the disease.

PMID- 9152295
TI  - Ivemark syndrome with asplenia in siblings.
AB  - We describe two siblings with Ivemark syndrome. In both cases, absent spleen,
      symmetric liver, and lungs with three lobes were associated with complex cardiac
      malformation. The syndrome was diagnosed prenatally in the second case by fetal
      echocardiography at the twentieth week of pregnancy. The autosomal recessive mode
      of inheritance of Ivemark syndrome is further supported by these cases.

PMID- 9152297
TI  - Childhood cancer and hypercalcemia: report of a case treated with pamidronate.
AB  - Hypercalcemia in a 4-year-old boy with non-Hodgkin lymphoma treated with
      pamidronate is presented. The child had relapsed disease with bone metastasis.
      Hypercalcemia is rare in children, and bisphosphonates are relatively new agents
      for the treatment of hypercalcemia. Information concerning their use in the
      treatment of hypercalcemia in childhood is limited. We found that pamidronate is
      effective and has no significant side effects in a child.

PMID- 9152296
TI  - Infantile hypophosphatasia: treatment options to control hypercalcemia,
      hypercalciuria, and chronic bone demineralization.
AB  - A 2-month-old child with infantile hypophosphatasia had hypercalcemia (3.49
      mmol/L (14 mg/dl)), nephrocalcinosis, and diminished bone mineral content.
      Hypercalcemia was corrected with calcitonin. Hypercalciuria and bone
      demineralization abated with chlorothiazide. Hypercalcemia is hypothesized to be
      related to normal bone resorption in conjunction with impaired bone
      mineralization. Chlorothiazide may alleviate this impairment.

PMID- 9152298
TI  - Oronasopharyngeal suction at birth: effects on arterial oxygen saturation.
AB  - The effect of oronasopharyngeal suction (ONPS) on arterial oxygen saturation
      (SaO2) is described in a controlled study of 30 normal term newborn infants. In
      15 of them, ONPS was performed immediately after birth. The SaO2 value was
      recorded through a pulse oximeter. The ONPS group had a significantly lower SaO2
      between the first and the sixth minutes of life and took longer to reach 86% and
      92% saturation. According to this study, ONPS should not be performed as a
      routine procedure in normal, term, vaginally born infants.

PMID- 9152299
TI  - Treatment of infantile primary pulmonary hypertension by intravenous infusion of
      lipo-prostaglandin I2 analog.
AB  - We used a new vasodilator, TTC-909 (a prostaglandin I2 analog incorporated in
      lipid microspheres), which produced marked reduction in the pulmonary arterial
      pressure and resistance in an infant with primary pulmonary hypertension.

PMID- 9152300
TI  - Inflammatory processes may predispose children to high-altitude pulmonary edema.
AB  - We investigated retrospectively whether the preexistence of inflammation
      producing illnesses such as viral respiratory tract infections contributed to the
      development of high-attitude pulmonary edema in children. We found that the large
      majority of native low-attitude children, but not adults, who had this form of
      edema after traveling to high altitude also had evidence of a preexisting
      illness. We speculate that the release of inflammatory mediators associated with
      these illnesses may be tolerated at sea level but may predispose children to
      increased capillary permeability when superimposed on hypoxia and, possibly, cold
      and exercise.

PMID- 9152301
TI  - Inhaled nitric oxide can cause severe systemic hypotension.

PMID- 9152302
TI  - Granulocyte colony-stimulating factor and neonatal infection.

PMID- 9152303
TI  - Safety of intravenous ketorolac therapy.

PMID- 9152304
TI  - Extracorporeal membrane oxygenation and clotting revisited.

PMID- 9152305
TI  - Back to the future of vascular surgery--why certain procedures become obsolete.

PMID- 9152306
TI  - Perioperative low molecular weight heparin for infrageniculate bypass.
AB  - PURPOSE: Recent studies suggest that subcutaneous low molecular weight heparin
      (LMWH) is a safe, effective alternative to intravenous heparin (IVH) for deep
      venous thrombosis. LMWH may also be a safe, effective alternative to IVH when
      necessary for lower extremity bypass procedures performed with
      polytetrafluoroethylene (PTFE) grafts. The purpose of this study was to compare
      subcutaneous LMWH with IVH for perioperative anticoagulation in patients who
      underwent infrageniculate bypass procedures with PTFE grafts. METHODS: Of 361
      lower extremity bypass operations performed at a single center over a 32-month
      period, 76 were to the tibial or below-knee levels using PTFE grafts for limb
      salvage. Seven patients were excluded because of absolute indications for
      perioperative IVH (ventricular thrombus in 1 patient, prosthetic valve in 2,
      cardiac dysrhythmia in 2, and documented hypercoagulable syndrome in 2), leaving
      68 patients (35 women; mean age, 69.8 years) with 69 bypass procedures for study.
      Grafts completed in the past 16 months were treated with LMWH (28 grafts; Oct.
      1994 to Jan. 1996) and were compared with 41 consecutive control grafts from the
      previous 16-month interval (Apr. 1993 to Oct. 1994) who received IVH. There were
      similar percentages of composite bypasses (IVH, 50%; LMWH, 46%), patients with
      tissue loss or gangrene (IVH, 56%; LMWH, 61%), and patients with prior
      ipsilateral bypass (IVH, 57%; LMWH, 56%) in each group. Age, sex, and
      atherosclerotic risk factors were also similar between the two groups. RESULTS:
      Morbidity rates (IVH, 19%; LMWH, 11%) and mortality rates (IVH, 2.5%; LMWH, 4%)
      were not significantly different. There were no significant differences in the
      number of grafts that failed before discharge (IVH, 1; LMWH, 0) or percentage of
      hemorrhagic complications (IVH, 15%; LMWH, 7%). The mean number of postoperative
      hospital days (IVH, 9.5; LMWH, 7.2; p < 0.009) and coagulation monitoring studies
      (IVH, 22; LMWH, 8.4; p < 0.0001) were significantly decreased in patients who
      were anticoagulated with LMWH. The mean number of days before conversion to oral
      anticoagulation (IVH, 7.3; LMWH, 8.0) did not differ significantly. CONCLUSIONS:
      When perioperative anticoagulation is deemed necessary, LMWH provides a safe,
      effective alternative to IVH for infrageniculate PTFE bypass grafting procedures.
      LMWH may reduce the number of postoperative hospital days and coagulation studies
      by allowing discharge before therapeutic anticoagulation with warfarin.

PMID- 9152307
TI  - Spontaneous closure of selected iatrogenic pseudoaneurysms and arteriovenous
      fistulae.
AB  - PURPOSE: We report our approach to the management of postcatheterization femoral
      artery pseudoaneurysms and arteriovenous fistulae in an attempt to determine the
      frequency of spontaneous resolution of selected lesions. METHODS: We studied 196
      pseudoaneurysms, 81 arteriovenous fistulae, and 9 combined lesions that were
      identified by duplex scan. Indications for immediate surgical repair included
      pseudoaneurysm greater than 3 cm, enlarging hematoma, pain, groin infection,
      nerve compression, limb ischemia, concomitant surgical procedure, and patient
      refusal or inability to comply with follow-up. All other lesions were observed.
      RESULTS: One hundred thirty-nine patients underwent prompt surgical repair, and
      147 patients were initially managed without operation. There were no limb
      threatening complications associated with nonoperative management in this subset
      of patients. Eighty-six percent of the lesions being observed resolved
      spontaneously within a mean of 23 days, whereas 14% required surgical closure for
      a variety of reasons (at a mean of 111 days after the initial diagnosis). There
      was no statistically significant difference in the rate of spontaneous
      pseudoaneurysm closure (89%) as opposed to fistulae (81%) (p < 0.17). By life
      table analysis, 90% of selected pseudoaneurysms had resolved by 2 months.
      Patients selected for observation underwent an average of 2.6 duplex scans per
      patient versus 1.4 scans per patient for those treated with immediate surgery (p
      < 0.01). CONCLUSION: The natural history of stable pseudoaneurysms and
      arteriovenous fistulae is benign and frequently results in spontaneous
      resolution, which allows properly selected patients to be managed without
      operation.

PMID- 9152308
TI  - Prostaglandin E2 synthesis and cyclooxygenase expression in abdominal aortic
      aneurysms.
AB  - PURPOSE: The purpose of this study was to evaluate the expression of
      prostaglandin E2 (PGE2) and the two cyclooxygenase isoforms (cox1 and cox2) in
      human abdominal aortic aneurysm (AAA) tissue. METHODS: Ten specimens each of
      normal aortas and aneurysmal aortas were collected and used for histologic
      analysis and whole organ culture. An enzyme-linked immunosorbent assay for PGE2
      was performed on the media from the aortic explant whole organ culture. An
      immunohistochemical analysis for PGE2 was performed, as was in situ hybridization
      for cox1 and cox2 on tissue sections. RESULTS: PGE2 production of AAA specimens
      was found to be 67,287 +/- 27,303 pg/ml as compared with 1698 +/- 858 pg/ml for
      normal aortic specimens (p < 0.001). PGE2 was localized by immunohistochemical
      analysis to the inflammatory infiltrate in AAAs. Minimal expression was noted in
      normal aortas. Using in situ hybridization, little expression of cox1 was noted
      in either the normal or the AAA specimens. Cox2 was expressed by macrophage-like
      cells within the inflammatory infiltrate of the AAA specimens but was not
      significantly expressed in the normal aorta. CONCLUSION: The expression of PGE2
      is associated with the pathogenesis of human AAAs. Its expression is localized to
      macrophage-like cells within the inflammatory infiltrate and is controlled by the
      cox2 isoform of cyclooxygenase. Cox2 is, therefore, a potential target for
      pharmacotherapy of AAAs.

PMID- 9152309
TI  - Anti-P-selectin antibody decreases inflammation and thrombus formation in venous
      thrombosis.
AB  - PURPOSE: Venous thrombosis and inflammation are interrelated. P-selectin
      contributes to activation of leukocyte-mediated inflammation. Therefore, we
      hypothesized that the neutralization of P-selectin would decrease vein wall
      inflammation and thrombosis. METHODS: Twelve baboons underwent infrarenal
      inferior vena caval balloon occlusion to induce thrombosis. Two groups of four
      baboons received neutralizing intravenous anti-P-selectin antibody (PSab) GA6 or
      CY1748 before occlusion and at days 2 and 4. Four baboons received saline control
      injections. One baboon per group was killed at days 2, 6, and 13, and at 2
      months. Analysis included phlebography, ultrasound, gadolinium (Gd)-enhanced
      magnetic resonance venography (reflecting vein wall inflammation), and
      histologic, morphometric, and protein evaluation of the vein wall. Thrombus
      presence or absence was assessed. RESULTS: By day 2 in PSab baboons, vein wall Gd
      enhancement was decreased in the mid-inferior vena cava and the right iliac vein
      (p < 0.05; GA6 vs control baboons), normalizing by 2 months. The mid-inferior
      vena cava revealed fewer neutrophils and total leukocytes in PSab baboons;
      however, for GA6 in the right iliac vein these decreases were not present despite
      the absence of Gd enhancement; they were decreased with CY1748. PSab baboons
      demonstrated significantly less thrombus than control baboons (p < 0.01, GA6 and
      CY1748 vs control baboons). CONCLUSIONS: Anti-P-selectin antibody decreases vein
      wall inflammation and thrombus formation. Inhibition of P-selectin may be useful
      in venous thrombosis prophylaxis.

PMID- 9152310
TI  - Percutaneous transluminal angioplasty and primary stenting of the iliac arteries
      in 288 patients.
AB  - PURPOSE: This study reports the initial and late results of percutaneous
      transluminal angioplasty (PTA) and intravascular stenting for atherosclerotic
      occlusive disease of the iliac arteries. METHODS: The preprocedural and
      postprocedural clinical records, arteriograms, segmental limb pressure
      measurements (ankle-brachial [ABI] and thigh-brachial [TBI] indexes), and pulse
      volume recordings of 288 patients who underwent PTA and primary stenting of the
      common iliac (354, 69.4%) and external iliac (156, 30.6%) arteries were reviewed.
      Initial and late clinical, hemodynamic, and angiographic success were assessed by
      objective criteria. Data on patients who underwent unsuccessful attempts at iliac
      stent placement are unavailable; results are not reported on an intent-to-treat
      basis. RESULTS: Clinical follow-up data (mean, 11.9 months) are available for 268
      of 288 patients (93.1%) and for 394 of 424 limbs (92.9%). The initial success
      rates, as determined by TBI, ABI, and clinical limb status, were 90.2%, 87.8%,
      and 74.6%, respectively. The Kaplan-Meier estimates of angiographic patency (101
      arteries) were 96%, 81%, and 73% at 6, 12, and 24 months. Cumulative patency
      rates were 84%, 76%, and 57% on the basis of TBI, ABI, and clinical limb status
      at 24 months. Factors associated with initial success included the need for
      multiple stents (p = 0.0001), a higher degree of initial stenosis (p = 0.0001),
      lower severity of baseline ischemia (p = 0.007), younger age (p = 0.0015), and
      the preprocedural patency of the ipsilateral superficial femoral artery (p =
      0.002). A higher degree of initial stenosis (p < 0.001) and superficial femoral
      artery patency (p = 0.004) were also associated with late success. CONCLUSIONS:
      PTA and stenting of the iliac arteries is associated with reasonable
      angiographic, hemodynamic, and clinical success. The outcome is favorably
      affected by higher initial severity of stenosis and greater extent of disease,
      lower severity of baseline ischemia, younger age, and by patency of the
      ipsilateral superficial femoral artery.

PMID- 9152311
TI  - Fibrin glue containing fibroblast growth factor type 1 and heparin with
      autologous endothelial cells reduces intimal hyperplasia in a canine carotid
      artery balloon injury model.
AB  - PURPOSE: Intimal hyperplasia plagues all types of vascular intervention. Early
      confluent re-endothelialization may attenuate the smooth muscle cell (SMC)
      proliferative response. We previously reported that fibroblast growth factor type
      1 (FGF-1) and heparin at relative concentrations of 10 ng/ml:250 U/ml delivered
      in a fibrin glue (FG) suspension can selectively stimulate endothelial cells (EC)
      and inhibit SMC proliferation in cell culture. This current study evaluates this
      surface treatment with and without seeded autologous ECs on intimal hyperplasia
      in a canine carotid artery balloon injury model. METHODS: Twenty-nine adult dogs
      underwent bilateral balloon injury to a 6 cm segment of their carotid arteries.
      The injury resulted in a reproducible removal of the intima and 4 to 6 medial
      lamellae. Nine dogs were used in part I to determine the percent retention of FGF
      1 and EC when applied in a FG suspension to the balloon-injured carotid arteries.
      Part 2 used the remaining 20 dogs to determine the effect of this surface
      treatment on intimal hyperplasia. In 10 group I dogs, FG (fibrinogen 32.1 mg/ml
      and thrombin 0.32 U/ml) containing FGF-1 (11 ng/ml) and heparin (250 U/ml) was
      applied to the luminal surface of one carotid artery, whereas the contralateral
      carotid artery underwent balloon injury alone. In 10 group II dogs, an identical
      FG preparation with FGF-1 and heparin was applied to the surface of one carotid
      artery, whereas the contralateral carotid artery received FG/FGF-1/heparin that
      also contained autologous ECs (P3; 5 x 10(4) to 10 x 10(4) cells/cm2). Five dogs
      from both group I and group II were killed at 10 days and the remaining 10 dogs
      at 30 days. Histologic analysis and computerized morphometric analysis were used
      to determine intimal and medial thickness and area, percent endothelialization,
      and medial SMC proliferative rate. RESULTS: There was no measurable neointima in
      any 10-day dog. There was no difference in neointimal area between the treatments
      in group I 30-day dogs. There was a significant decrease in maximal neointimal
      area, intima/media thickness ratio, and intima/media area ratio in group II 30
      day dogs that were treated with FG/FGF-1/heparin plus EC. There was an
      insignificant increase in percent EC coverage and an insignificant decrease in
      medial SMC proliferative rate in group II 10-day dogs treated with FG/FGF
      1/heparin plus EC. CONCLUSIONS: In this canine carotid model, FG with FGF-1 and
      heparin did not induce significant intimal or medial thickening after 10 or 30
      days when compared with vessels that were only balloon-injured. The seeding of
      autologous ECs within the FG/FGF-1/heparin suspension caused a reduction in
      neointima formation with no concomitant medial thickening 30 days after injury.
      The use of FG to locally deliver FGF-1 and ECs may have clinical relevance in the
      inhibition of intimal hyperplasia.

PMID- 9152312
TI  - Duplex morphologic features of the reconstructed carotid artery: changes
      occurring more than five years after endarterectomy.
AB  - PURPOSE: To determine the late morphologic appearance of the carotid artery after
      endarterectomy and to relate the morphologic characteristics to the development
      of recurrent carotid stenosis and subsequent neurologic symptoms. METHODS: Eighty
      eight carotid reconstructions (51% included patch angioplasty) in 82 patients
      were studied 5 or more years after carotid endarterectomy. Duplex color flow
      imaging was used to determine morphologic characteristics of the carotid
      endarterectomy site and to document the occurrence, time interval, and
      progression of recurrent internal carotid artery stenosis. The spatial
      orientation of recurrent wall thickening, presence of calcium, arterial wall
      texture, and presence of laminar flow were evaluated. Recurrent stenoses were
      categorized using standard duplex criteria. RESULTS: The mean duration of follow
      up was 99 months (range, 60 to 138 months). Arterial wall calcium was identified
      in 23% (n = 18), a smooth luminal surface in 57% (n = 46), and laminar flow in
      52% (n = 42). Recurrent wall thickening developed in 58 vessels (66%), involving
      the posterior segment of the vessel in 95%, and anterior, lateral, or medial
      aspects in 24% (n = 14). Restenosis > 50% diameter reduction occurred in 4% of
      common carotid arteries (n = 3) and in 15% of internal carotid arteries (n = 13).
      Ten of the internal carotid artery restenoses occurred after a mean of 76 months
      (range, 13 to 132 months), and the three remaining patients had asymptomatic
      occlusions after a mean of 61 months (range, 1 to 96 months). Neurologic events
      referable to the reconstructed carotid artery occurred in three patients at a
      mean of 77 months; two were a result of recurrent carotid disease. One
      symptomatic patient and two asymptomatic patients (3.7%) underwent a second
      ipsilateral reconstruction for recurrent high-grade stenosis. CONCLUSIONS: The
      carotid artery remains smooth, with laminar flow and without calcification, in
      the majority of reconstructions that were observed over a long term. There is a
      low incidence of subsequent ipsilateral neurologic events or significant
      recurrent stenosis, both of which usually occur late in the postoperative period.
      This study documents the long-term durability of carotid endarterectomy in
      providing risk reduction for stroke.

PMID- 9152314
TI  - Cell adhesion molecules and insulin-like growth factor-1 in vascular disease.
AB  - PURPOSE: Recent advances in the understanding of the biologic mechanisms of
      vascular diseases suggest that multifactorial stimulation of the endothelial cell
      and its subsequent adhesion to leukocytes is a prerequisite to the formation of
      atherosclerotic and restenotic lesions. As leukocyte-endothelial cell interaction
      is coordinated by a variety of cell adhesion molecules (CAMs), we hypothesized
      that the expression of certain CAMs is up-regulated in the vasculature of
      patients who have peripheral vascular disease. In addition, we proposed that
      insulin-like growth factor-1 (IGF-1) increases monocyte-endothelial adhesion by
      means of upregulation of these CAMs. METHODS: Using immunohistochemical
      techniques, the expression of intracellular adhesion molecule-1 (ICAM-1),
      vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin was
      examined in human vascular disease specimens. Normal aortas obtained from the
      organ retrieval system were studied as control specimens. Adhesion studies
      between human umbilical vein endothelial cells (HUVECs) incubated with IGF-1 and
      purified human blood monocytes labeled with 51chromium were completed. Western
      blotting and flow cytometry were performed to show CAM expression on IGF-1
      treated HUVECs. RESULTS: Of the CAMs, ICAM-1, P-selectin, and E-selectin were
      distinctly increased in diseased specimens when compared with control specimens
      (p < 0.05). Adhesion studies showed an increase in monocyte-endothelial cell
      adhesion of as much as 40% to 45% (p < 0.01) over baseline, with peak adherence
      occurring 4 hours after treatment with IGF-1. IGF-1 increased adherence in a dose
      and time-dependent manner. The threshold concentration of IGF-1 that induced
      increased adhesion was 20 ng/ml, with a maximum effect occurring at 150 ng/ml.
      This increased adhesion was attenuated by pretreatment with IGF-I receptor
      antibody, as well as with genistein and herbimycin-A, which are potent and
      selective tyrosine kinase inhibitors. Increased adhesion correlated with an
      increase in the expression of CAMs on the surface of the HUVECs. An additive
      effect on adhesion was observed between IGF-1 and tumor necrosis factor-alpha
      (TNF-alpha) and endothelin-1 (ET-1). Finally, immunohistochemical analysis of
      human vascular disease specimens revealed an increased expression of IGF-1
      receptors as compared with control specimens (p < 0.05). CONCLUSIONS: These
      results suggest that IGF-1 may be important in the pathogenesis of peripheral
      vascular disease by increasing endothelial cell-monocyte adhesion by means of an
      increase in the expression of ICAM-1 and VCAM-1.

PMID- 9152313
TI  - Defective fibrinolysis occurs after infrainguinal reconstruction.
AB  - PURPOSE: Early thrombosis of infrainguinal bypass grafts may occur as a result of
      hypercoagulable states. Major surgical procedures are known to induce a
      procoagulant state that is manifested in part by reduced endogenous fibrinolytic
      activity or fibrinolytic shutdown. This study was performed to assess the timing
      and biologic mechanism of fibrinolytic shutdown after infrainguinal bypass
      procedures by direct assay of the serologic markers of in vivo fibrinolytic
      activity. METHODS: Twenty patients underwent infrainguinal bypass procedures
      under epidural anesthesia. Endogenous fibrinolytic activity was assessed by
      measurement of tissue plasminogen activator (tPA) and its naturally occurring
      inhibitor, plasminogen activator inhibitor (PAI-1). The tPA and PAI-1 antigen
      (total protein) levels were determined using enzyme-linked immunosorbent assays,
      and measurements of in vivo biologic activity were performed using an amidolytic
      method. Measurements of tPA and PAI-1 were made before surgery, after surgery,
      and on postoperative days 1, 2, 7, and 30. RESULTS: The mean preoperative PAI-1
      activity was 20.6 +/- 1.4 arbitrary units (AU)/ml, which was higher than that of
      an age-matched population without severe atherosclerosis. PAI-1 activity rose
      significantly after surgery (29.6 +/- 2.2 AU/ml; p = 0.002) and remained elevated
      through the second day after surgery. Preoperative tPA activity level was 2.04 +/
      0.59 IU/ml and fell to 0.79 +/- 0.23 IU/ml (p = 0.046) immediately after the
      bypass procedure. All serologic indicators of fibrinolytic shutdown returned to
      baseline levels by 72 hours after surgery. No early graft thrombosis or other
      atherothrombotic complications occurred in these study patients. CONCLUSIONS:
      Defective endogenous fibrinolytic activity occurs in the early postoperative
      period after infrainguinal bypass grafting procedures. Diminished endogenous
      fibrinolytic activity in these patients appears to be mediated by a combination
      of reduced tPA activity and significantly increased PAI-1 activity. No practical
      method is available to directly treat postoperative fibrinolytic shutdown, but
      postoperative antithrombotic therapy may be useful during this period to prevent
      early graft occlusion related to a relative hypercoagulable state.

PMID- 9152315
TI  - Carotid endarterectomy for recurrent stenosis.
AB  - PURPOSE: The purpose of this study was to report our results in the surgical
      management of recurrent carotid stenosis (RCS) after carotid endarterectomy
      (CEA). METHODS: In a 20-year period, we performed 1209 CEAs; 82 operations (6.8%)
      were for RCS. There were 33 men and 36 women, with an average age of 66.3 years.
      Nine patients underwent two redo CEAs and two patients underwent three redo CEAs
      for either bilateral recurrence or a second recurrence on the same side. Overall,
      10 patients were identified with a second recurrence. RESULTS: The average time
      to presentation with RCS was 65 months (range, 3 to 361 months). The majority of
      patients (66%) were symptomatic, 34% had transient ischemic attacks, 17% had
      amaurosis fugax, 9% had strokes, and 6% had nonhemispheric symptoms. Before
      repair, angiograms were obtained. Patch repair was performed in 61 procedures
      (74%), 41 with vein, 11 with Dacron, and nine with polytetrafluoroethylene.
      Autogenous or synthetic bypass grafts were used in 20 procedures (24%), vein in
      eight, Dacron in two, and polytetrafluoroethylene in 10. In one patient, an
      occluded internal carotid artery was ligated and an endarterectomy of the
      external carotid artery was performed without a patch. The operative stroke rate
      was 4.8%. Minor complications included transient or permanent cranial nerve
      deficits in 7.3% and wound hematomas in 2.4%. CONCLUSION: Although repeat
      endarterectomy to treat RCS is technically more demanding, it can be performed
      safely. Long-term follow-up examination shows that a second recurrence may
      develop, and we recommend serial noninvasive testing.

PMID- 9152317
TI  - Carotid endarterectomy in women versus men: patient characteristics and outcomes.
AB  - PURPOSE: To examine and compare the results of carotid endarterectomy in women
      and men in a single-group experience. METHODS: A review of a consecutive series
      of 426 carotid endarterectomy procedures performed over an 11-year period.
      RESULTS: Women and men who underwent carotid endarterectomy were remarkably
      similar in nearly all characteristics except that women were less likely to have
      clinically overt coronary artery disease. Women were more likely than men to
      undergo patch closure of the carotid artery, but details of surgery and hospital
      stay were otherwise similar. A trend toward higher perioperative stroke risk in
      women was not significant, and late ipsilateral stroke risk was comparable in
      women and men. Women enjoyed a better late survival rate, presumably related to
      their lower prevalence of coronary artery disease. CONCLUSIONS: Women enjoyed
      similarly low risks of perioperative and late stroke and a better long-term
      survival rate when compared with men who underwent carotid endarterectomy.
      Further experience and longer follow-up in prospective randomized trials may
      provide more definitive information regarding the comparative efficacy of carotid
      endarterectomy in women and men, but our results suggest that absolute results
      are similar and excellent in both women and men.

PMID- 9152316
TI  - Combined exposure to cigarette smoke and hypercholesterolemia decreases
      vasorelaxation of the aorta.
AB  - PURPOSE: The purpose of this study was to determine the physiologic effects of
      cigarette smoke exposure and dietary cholesterol on the availability of nitric
      oxide in aortic vascular rings. METHODS: Four groups of New Zealand White rabbits
      were placed in an air flow chamber for 3 hours per day for 8 weeks. Two of these
      groups were exposed to smoke from 600 cigarettes per day 5 days a week added to
      the chamber inflow by a robotic smoke generator. One of these groups was made
      hypercholesterolemic by being fed a 0.3% cholesterol diet. Two groups of rabbits
      were similarly placed in the air flow chamber but without smoke exposure, of
      which one group was also made hypercholesterolemic. After an 8-week period, the
      rabbits were killed and the infrarenal aortas were excised. The vessels were cut
      into 3 mm rings and suspended from tension transducers. The rings were contracted
      with potassium chloride to determine vessel integrity. Then one ring from each
      aorta was maximally contracted with norepinephrine, and the experimental ring was
      contracted to 50% of maximum. Relaxation of the rings in response to incremental
      doses of acetylcholine was measured. RESULTS: No significant differences were
      seen in contraction to potassium chloride or norepinephrine in any group. A
      significant decrease in acetylcholine-mediated relaxation was seen only in the
      smoke-exposed, cholesterol-fed group. CONCLUSIONS: Endothelial damage, as
      measured by acetylcholine-mediated vasorelaxation, occurs in the infrarenal aorta
      in rabbits that are exposed to both cigarette smoke and elevated dietary
      cholesterol. Cigarette smoke exposure alone or hypercholesterolemia alone in this
      model did not result in significant alteration in acetylcholine-mediated
      vasorelaxation.

PMID- 9152318
TI  - Predictors of long-term patient survival after in situ vein leg bypass.
AB  - PURPOSE: The objective was to determine the long-term survival rates of patients
      who undergo distal arterial bypass surgery and to identify the preoperative
      factors that are predictive of survival. METHODS: Three hundred fifty-eight
      consecutive in situ distal leg bypass procedures were performed between July 1986
      and December 1995. The relationship between 13 preoperative variables and late
      survival were determined using both univariate (Kaplan-Meier) and multivariate
      (Cox regression) statistical techniques. RESULTS: The cumulative survival rates
      at 1, 3, 5, and 7 years were 86.6% +/- 2.0%, 63.2% +/- 3.0%, 46.9% +/- 3.4%, and
      35.3% +/- 3.8%, respectively. Using Cox regression, four significant variables
      were found to be associated with lower late survival rates: male gender,
      diabetes, chronic renal insufficiency (patients with creatinine levels greater
      than or equal to 1.7 mg/dl or 150 SI units), and a history of cerebrovascular
      disease (p < 0.001 for model). When none of these four variables were present,
      the predicted 5-year survival rate was 71%, whereas the survival rate was reduced
      to 43% to 60% when one was present, 23% to 42% when two were present, 8% to 22%
      when three were present, and 2% when all four were present. CONCLUSIONS: This
      study defines the long-term survival rates in a cohort of patients after
      undergoing distal bypass surgery and demonstrates that certain preoperative
      factors are predictive of late survival. Knowledge of these factors may be useful
      to assist in individual operative decisions between aggressive attempts at distal
      revascularization versus primary amputation.

PMID- 9152319
TI  - Indium In-111 pentetreotide scintigraphy: application to carotid body tumors.
AB  - PURPOSE: This study was conducted to investigate and illustrate the use of Indium
      In-111 pentetreotide scintigraphy as it applies to carotid body tumors (CBT).
      Localization has relied primarily on ultrasonography, computed tomography, and
      magnetic resonance imaging with angiographic confirmation. These methods only
      assess the cervical bifurcation without providing an evaluation of metastasis in
      patients without symptoms or recurrence in patients after surgery. METHODS:
      Indium In-111 pentetreotide scintigraphy was used in five patients with a
      diagnosis of CBT. Four patients were evaluated after surgical excision for
      evidence of tumor recurrence. One patient was evaluated before excision for
      diagnostic confirmation. RESULTS: No evidence of tumor recurrence was
      demonstrated in the four patients who had undergone previous CBT excision. One of
      these patients had increased activity in the pituitary, later confirmed as an
      enlarged pituitary without evidence of an adenoma with computed tomography. The
      diagnosis of CBT was confirmed in the patient evaluated before surgery. This
      patient also had increased activity in the occipital region, confirmed as the
      site of previous ischemia on computed tomography. CONCLUSION: Indium In-111
      pentetreotide scintigraphy is a new innovative method for viewing neuroendocrine
      tumors. Its potential lies not only in tumor localization but also in
      identification of recurrent tumor at the operative site and metastatic disease.

PMID- 9152320
TI  - Aminoterminal propeptide of type III procollagen in the follow-up of patients
      with abdominal aortic aneurysms.
AB  - PURPOSE: We evaluate here whether serial changes in the concentration of the
      aminoterminal propeptide of type III procollagen (PIIINP) in serum bear any
      relationship to the rate of abdominal aortic aneurysm (AAA) expansion and whether
      serum PIIINP has any predictive value with respect to the rupture event. METHODS:
      One hundred thirty-nine patients with asymptomatic AAAs were followed-up at
      intervals of 6 to 12 months by means of a clinical examination, B-mode ultrasound
      scan, and serum markers of collagen metabolism. Similar laboratory samples were
      also obtained from 18 patients who had a rupture of the AAA as their primary
      symptom soon after onset. RESULTS: The primary correlation between serum PIIINP
      and AAA diameter was 0.22 (p = 0.01), and that between serum PIIINP and the
      thickness of the thrombus was 0.49 (p = 0.001). Toward the end of the follow-up,
      however, the correlation increased to 0.55 (p = 0.002) for serum PIIINP and
      diameter, but remained at 0.42 (p = 0.02) for serum PIIINP and the thickness of
      the thrombus. Serum PIIINP values were very high among the 18 patients who had
      ruptured AAAs. CONCLUSIONS: Acceleration of AAA growth is reflected in serum
      PIIINP, and a marked elevation of serum PIIINP during follow-up of a patient with
      an AAA may predict an approaching rupture event.

PMID- 9152321
TI  - Cellular content and permeability of intraluminal thrombus in abdominal aortic
      aneurysm.
AB  - PURPOSE: A pathologic feature commonly associated with abdominal aortic aneurysms
      is the presence of variably sized and shaped intraluminal thrombus, which may be
      fundamental to the disease process. However, the precise role of the intraluminal
      thrombus in the formation, enlargement, and rupture of abdominal aortic aneurysms
      is unknown. The hypothesis tested in this study was whether there were structural
      features of aortic thrombi to suggest that it may be involved in the pathogenesis
      of abdominal aortic aneurysms. We have investigated this hypothesis using a
      variety of structural and biochemical techniques. METHODS: Tests performed were
      light, transmission, and scanning electron microscopy; fluid permeability
      measurements; and Western blots. RESULTS: Intraluminal thrombus found in
      abdominal aortic aneurysms is structurally complex and is traversed from the
      luminal to abluminal surface by a continuous network of interconnected
      canaliculi. Quantitative microscopic analysis of the thrombus shows cellular
      penetration for at least 1 cm from the luminal surface of the thrombus. Macro
      molecular penetration may be unrestricted throughout the entire thickness of the
      thrombus. Fibrin deposition occurred throughout the thrombus, whereas fibrin
      degradation occurred principally at the abluminal surface. CONCLUSIONS: These
      principally structural studies support the hypothesis that the thrombus is a self
      sustaining entity that may have significance in the pathophysiologic mechanism of
      abdominal aortic aneurysms.

PMID- 9152322
TI  - Bilateral iliac artery aneurysms and pancake kidney: a case report.
AB  - Renal fusion and ectopia are anomalies of the proximal urinary tract that present
      a special challenge to vascular surgeons. We present a rare case of bilateral
      iliac artery aneurysms in a 70-year-old man with a fused pancake kidney. The
      patient underwent preoperative evaluation with a computed tomographic scan and
      angiographic examination, followed by bilateral iliac artery reconstruction.
      Pancake kidney is a rare renal anomaly, and its association with aortoiliac
      disease has been referred to only one other time in the literature. Successful
      management is dependent on preoperative recognition of the renal anomaly,
      aortographic examination to delineate renal blood supply, and careful operative
      preservation of renal vasculature.

PMID- 9152323
TI  - Blunt disruption of the abdominal aorta: report of a case and review of the
      literature.
AB  - A 71-year-old woman had an abdominal aortic disruption as a belted passenger in a
      motor vehicle accident. The diagnosis was unexpected, and the patient died during
      surgery. There have been 54 patients operated with this diagnosis since 1953; our
      patient was the fifty-fifth. This is an unusual injury, because the aorta is well
      protected in this position. Thoracic aortic injuries are much more common (20
      times) than abdominal injuries. The causes are motor vehicle accidents, blows to
      the abdomen, explosions, and falls. Obstructing lesions such as thrombosis and
      intimal dissection are the more common presentation. False aneurysms occur
      occasionally. Free rupture has a very high and immediate mortality rate, and few
      patients arrive at the hospital alive. Diagnosis can be clinical, based on distal
      ischemia and neurologic abnormalities, or made with Doppler scanning,
      ultrasonography, computed tomography, or arteriography. Two thirds present
      acutely and one third subsequently months or even years after the original
      injury. Treatment consists of flap suture, thrombectomy, bypass grafting in more
      extensive injury, or extra-anatomic bypass in the face of severe contamination.
      Recently, endoluminal stenting has successfully been used, avoiding an abdominal
      operation completely.

PMID- 9152324
TI  - Traumatic abdominal aortic pseudoaneurysm causing biliary obstruction: a case
      report and review of the literature.
AB  - A traumatic pseudoaneurysm of the suprarenal abdominal aorta was diagnosed in a
      58-year-old man 32 years after he received a gunshot wound to the abdomen.
      Epigastric pain and obstructive jaundice were the presenting symptoms. Repair was
      performed by intraluminal polytetrafluoroethylene patch aortoplasty with
      resolution of the biliary obstruction. The literature on traumatic abdominal
      aortic pseudoaneurysm is reviewed and reveals that this report is the first to
      describe biliary obstruction caused by such a lesion.

PMID- 9152325
TI  - Saccular aneurysm in the right-sided aortic arch: a successfully corrected case.
AB  - We report the surgical treatment of a rare case of true aortic aneurysm in a
      right-sided aortic arch. A 49-year-old female patient with obstructive
      respiratory problems demonstrated a true aneurysm with a diameter of 58 mm
      located at the right-sided aortic arch between the right carotid artery and right
      subclavian artery. Surgery was successfully performed by replacing the arch
      including the aneurysm with a prosthetic graft. The positions of true aneurysms
      in the right-sided aortic arch can be divided into two subtypes: first, the
      transverse arch between the right carotid artery and right subclavian artery, and
      second, the base of the subclavian artery, the Kommerell's diverticulum. The
      region is informative for consideration of the surgical approach toward aneurysms
      of this entity.

PMID- 9152326
TI  - Treatment for abdominal aortic aneurysm in a patient with hemophilia A: a case
      report and review of the literature.
AB  - A 77-year-old man with abdominal aortic aneurysm (AAA) was referred to our
      department. His AAA, which was 6 cm in diameter, was found incidentally with
      ultrasonography. On admission the diagnosis of hemophilia A was made for the
      first time in his life because activated partial thromboplastin time was
      decreased to 32.3% and factor VIII coagulant activity was 2.1% (normal range 40%
      to 140%). Recombinant factor VIII supplemental therapy was continued during
      surgery to maintain his factor VIII level within the normal range. His AAA was
      operated successfully with bifurcated graft replacement. No unusual bleeding
      complications occurred during his hospitalization. With proper preparation the
      patient with AAA and hemophilia A can safely undergo surgical treatment. Three
      other cases of AAA with hemophilia in the English literature were reviewed, and
      this is the oldest patient with hemophilia who underwent AAA surgery.

PMID- 9152327
TI  - Multiple idiopathic arterial aneurysms in children: a case report and review of
      the literature.
AB  - A 6-year-old boy from China presented initially at 2 years of age with a
      pulsatile mass in his right antecubital fossa. He was not fully evaluated until
      the age of six years, when pan-angiography and computed axial tomography scan
      revealed multiple aneurysms of his right brachial artery, right radial artery
      aneurysms, an infrarenal aortic aneurysm, and a right internal carotid artery
      aneurysm in the region of the cavernous sinus. The patient underwent uneventful
      repairs of both the abdominal aortic aneurysm and the multiple aneurysms of the
      right arm. Pathologic evaluation was significant for medial fibrosis of the
      arterial wall with decreased and disordered elastin fibers. Review of the
      previously reported cases in children indicate the upper extremity arteries are
      involved in 92% of patients, the aortoiliac region in 92% of patients, and the
      renal/mesenteric vessels in 77% of cases. Lower extremity and cerebrovascular
      arteries are involved to a lesser extent. Children with peripheral aneurysms
      should have pan-angiography performed before treatment is begun. Surgical repair
      in these cases has been excellent.

PMID- 9152328
TI  - Regarding "Selection of patients for cardiac evaluation before peripheral
      vascular operations".

PMID- 9152329
TI  - Regarding "Iliac vein compression syndrome: case report and review of the
      literature".

PMID- 9152330
TI  - Regarding "The endarterectomy-produced common carotid artery step: a harbinger of
      early emboli and late restenosis".

PMID- 9152331
TI  - Regarding "Evaluation of carotid artery stenosis: is duplex ultrasonography
      sufficient?".

PMID- 9152332
TI  - Regarding "Complications of iliac artery stent deployment".

PMID- 9152333
TI  - Regarding "Upper dorsal thoracoscopic sympathectomy for palmar hyperhidrosis:
      improved intermediate-term results".

PMID- 9152334
TI  - Are we committed to improving the safety of health care?

PMID- 9152335
TI  - The Australian Red Cross Blood Service.

PMID- 9152336
TI  - HTLV-I and blood safety: let the community decide.

PMID- 9152337
TI  - Endemic STDs in remote communities: the challenge for STD control.

PMID- 9152338
TI  - Reporting of adverse events in hospitals in Victoria, 1994-1995.
AB  - OBJECTIVE: To describe the nature and frequency of adverse events (AEs) reported
      in routine inpatient data collection. DESIGN: Retrospective analysis of data from
      the Victorian Inpatient Minimum Database. SETTING: All public (135) and private
      (112) acute-care hospitals in Victoria, 1994-1995. PARTICIPANTS: All patients
      with separations recording an E-code identified as an AE through the
      International classification of diseases, ninth revision (ICD-9), classification
      system. MAIN OUTCOME MEASURES: Australian national diagnosis-related groups (AN
      DRGs) associated with AEs; prevalence of major organ system disease in each of
      the AE groups; AE rates by hospital type; and impact of AEs on discharge
      destination, or death. RESULTS: AEs were recorded in 5% of separations, with
      incidence increasing with patient age. Most (81%) were complications after
      surgery or other procedures (E878-E879); 19% were adverse drug effects (E930
      E949) and 1.7% were misadventures (E870-E876). The most frequently reported
      complications were infections, haemorrhage and pneumonia. AN-DRGs--joint
      replacement of the lower limb, bowel excision and hysterectomy--contributed most
      to the volume of AEs, while the greatest risk was associated with ventricular
      shunt, major organ transplantation and surgery for complicated injuries. The in
      hospital death rate in patients with AEs was 2.9% (95% confidence interval [95%
      CI], 2.7%-3.2%), compared with 1.3% (95% CI, 1.0-1.4) in those without an AE. Of
      patients with an AE, fewer were discharged directly home, and higher proportions
      were discharged to other acute-care facilities or nursing homes compared with
      those without an AE. CONCLUSION: Inpatient data collection can provide
      information about AE rates associated with individual procedures, and the nature
      of these AEs. It can be used by hospitals to direct and complement their own
      quality improvement activities. Its limitation is that it cannot identify the
      severity or long term outcome of AEs.

PMID- 9152339
TI  - A profile of inpatient STD-related pelvic inflammatory disease in the Top End of
      the Northern Territory of Australia.
AB  - OBJECTIVE: To obtain a profile of inpatient STD-related pelvic inflammatory
      disease (PID) in the Top End of the Northern Territory. DESIGN: Review of case
      records. SETTING: The Royal Darwin Hospital, the tertiary referral centre for the
      Top End, during the three years from June 1991 to May 1994. PATIENTS: All
      admissions with a diagnosis of STD-related PID. MAIN OUTCOME MEASURES: The
      presentation and incidence of STD-related PID in Aboriginal and non-Aboriginal
      women. RESULTS: PID was the reason for 14% of admissions of Aboriginal women and
      2% of non-Aboriginal women. Of 175 episodes of PID in 169 patients admitted over
      the three years of the study, 41 (23%) had gonorrhoea, 64 (37%) had chlamydia and
      7 (4%) had both organisms isolated on genital swab. Aboriginal women were more
      than twice as likely to have gonorrhoea (38% versus 18%; risk ratio, 2.12; 95%
      confidence interval, 1.27-3.53) as non-Aboriginal women. Median time from first
      symptoms to presentation was six days. All gonococcal isolates were penicillin
      susceptible. CONCLUSIONS: STD-related pelvic inflammatory disease is an important
      problem among women in the Top End of the Northern Territory. As PID is a
      preventable illness, further measures aimed at prevention and earlier, more
      effective treatment of STDs that cause PID are urgently required.

PMID- 9152340
TI  - Urinary diagnosis of gonorrhoea and Chlamydia in men in remote aboriginal
      communities.
AB  - AIMS: (1) To evaluate the acceptability and validity of an intervention based on
      urine tests for diagnosis and treatment of gonorrhoea and chlamydia in men in
      remote Aboriginal communities. (2) To provide a prevalence estimate of these
      infections in the male population in the surveyed communities. METHODS: First
      void urine samples from 460 men in remote communities and 33 men in the Alice
      Springs Gaol were tested for gonorrhoea and chlamydia with at least one of
      polymerase chain reaction (PCR), enzyme immunoassay (EIA) and culture (gonorrhoea
      only). RESULTS: One hundred and three men (20.9%) were infected with gonorrhoea
      or chlamydia. The prevalence of infection for gonorrhoea only was 11.7%, for
      chlamydia only 4.1% and for dual infection 5.1%. Eighty-eight infected men and 45
      of their sexual partners were recorded as having been treated within two months
      of testing. PCR tests detected the largest number of infections and were the
      easiest to use. CONCLUSIONS: The prevalence of these infections was higher than
      anticipated. Urine PCR tests were acceptable to men and are well suited to the
      remote-community setting. As an effective alternative to urethral swabs, they
      permit a range of community-based strategies to address high rates of infection
      with gonorrhoea and chlamydia.

PMID- 9152341
TI  - A Queensland family with ciguatera after eating coral trout.
AB  - Ciguatera (poisoning caused by eating fish contaminated with algal toxins) is
      usually diagnosed clinically. We describe a Queensland family of four (including
      a pregnant woman) with ciguatera, confirmed by bioassay of the implicated fish
      for ciguatoxin. All four recovered, illustrating the effectiveness of treatment
      with intravenous mannitol. At birth, the infant appeared to suffer no adverse
      effects attributable to ciguatera; to our knowledge, this is the first report of
      the effect of severe ciguatera in the first trimester of pregnancy.

PMID- 9152342
TI  - Is screening of Australian blood donors for HTLV-I necessary?
AB  - OBJECTIVE: To re-examine the 1992 decision by Australian Red Cross for its blood
      banks to screen blood donors for antibody to human T-cell lymphotropic virus type
      I (HTLV-I) by determining the risk of its transmission by blood transfusion.
      METHODS: Data on patterns of return behaviour by repeat blood donors in Victoria
      were modelled to deduce the number of donors giving repeat donations in Australia
      from March 1993 to December 1995. Data on annual donor and issued cellular blood
      products from 1992 to 1995 were obtained from national Red Cross statistics. From
      the numbers of donations given by repeat donors, together with the number of new
      donors, the number tested for HTLV-I was deduced. The number and characteristics
      of donors screened positive for HTLV-I antibody were collated. The crude
      prevalence of HTLV-I was calculated by dividing the number of donors with HTLV-I
      by the total number of donors (repeat donors and new donors). The incidence of
      HTLV-I was calculated by dividing the number of seroconversions in repeat donors
      by the cumulative period of donor exposure. RESULTS: Sixteen homologous and five
      autologous donors were found to be positive for HTLV-I; none seroconverted and no
      clear risk factors for HTLV-I were identified. The prevalence of HTLV-I in
      Australian donors is 1 in 100,000 and the incidence less than 1 in 1 million
      person-years. In the absence of HTLV-I screening, the calculated risk of a
      transfused patient developing HTLV-I infection is 1 in 370,000, with a risk of
      developing HTLV-I disease of 1 in 9 to 15 million. CONCLUSION: Three possible
      future courses of action for screening for HTLV-I are to screen every donation,
      to screen only new donors or to discontinue screening altogether. Using the
      information in this study, public discussion should be encouraged to assist
      stakeholders to agree on an acceptable level of risk and an appropriate level of
      screening for HTLV-I in Australia.

PMID- 9152343
TI  - Every defect a treasure: learning from adverse events in hospitals.

PMID- 9152344
TI  - An update on the diagnosis and management of respiratory illness.

PMID- 9152345
TI  - The patient with chronic cough.
AB  - The most effective management of cough is specific therapy, which results in a
      greater than 90% response rate, so the cause should be thoroughly investigated. A
      chest x-ray should be taken early in the clinical investigation of chronic cough.
      The three most common causes of chronic cough when chest x-rays are normal are
      postnasal drip, bronchial asthma and gastro-oesophageal reflux. Chronic cough has
      more than one cause in 20% of patients, so therapy may need to be directed at
      multiple causes. Gastro-oesophageal reflux may complicate cough from any cause
      because a cough-reflux feedback cycle can develop. Hence, a four-week trial of an
      H2-receptor antagonist is indicated in patients with unexplained chronic cough
      where the history, physical examination, chest x-ray, lung function tests,
      ear/nose/throat examination and home peak flow monitoring all fail to elucidate a
      cause. Non-specific therapy should be reserved for when no diagnosis can be made,
      or when therapy is likely to be ineffective (e.g., lung malignancy).

PMID- 9152346
TI  - End-of-life decisions in Australian medical practice.

PMID- 9152347
TI  - End-of-life decisions in Australian medical practice.

PMID- 9152348
TI  - End-of-life decisions in Australian medical practice.

PMID- 9152349
TI  - Prevalence of hepatitis G virus antibodies in Queensland blood donors.

PMID- 9152350
TI  - Challenge and response: HIV in Asia and the Pacific.

PMID- 9152351
TI  - Helmets and bicycle-related injuries in Queensland.

PMID- 9152352
TI  - Day ophthalmic surgery: aspects of perioperative care.

PMID- 9152353
TI  - Malaria, mefloquine and the mind.

PMID- 9152354
TI  - Cardiac transplantation in New Zealand: eight years experience.
AB  - Between December 1987 and December 1995, 62 patients underwent orthotopic cardiac
      transplantation at Green Lane Hospital. Their cardiac dysfunction resulted from
      dilated cardiomyopathy (32), coronary artery disease (21), rheumatic heart
      disease (7), congenitally corrected transposition of the great arteries (1) and
      hypertrophic cardiomyopathy (1). Before transplantation all patients were in New
      York Heart Association (NYHA) functional class III or IV. Eight patients (13%)
      died in the perioperative period and a further seven (11%) died 1 to 4 years
      after transplantation. Actuarial 1 and 3 year survival was 87% and 80%
      respectively. Forty-five of forty-seven surviving patients were in NYHA
      functional class I at the time of analysis. The results confirm that cardiac
      transplantation has a limited but valuable role in the treatment of end stage
      myocardial dysfunction.

PMID- 9152355
TI  - Otitis media treatment in New Zealand general practice.
AB  - AIMS: To compare incidence and general practice treatments for acute (AOM),
      serous (OME), and recurrent (ROM) otitis media in New Zealand. METHODS: A
      retrospective analysis of 2901 consultations for otitis media was undertaken.
      Specific diagnostic groups were compared for antibiotic treatments offered,
      duration of therapy, and treatment success. Twenty New Zealand general practices
      contributed 290100 computerised consultation records generated between 1 July
      1993 and 30 June 1994. Records from 2089 otitis media patients were examined to
      determine incidence and treatment success. RESULTS: Most initial acute otitis
      media and recurrent otitis media presentations resulted in antibiotic treatment
      (96.6% and 94.9%): fewer otitis media with effusion presentations (77.6%) were
      initially treated with antibiotics. Age and treatment success were significantly
      associated for patients with acute otitis media: patients < 2 years were least
      likely to be successfully treated (p < 0.0001). There was no difference in
      success rates between antibiotic and no antibiotic therapies. Antibiotic therapy
      duration ranged from < 6 days to 40 days. Shorter courses were as likely as
      longer courses to be successful for all diagnoses. CONCLUSIONS: The outcome of
      otitis media episodes is more closely related to patients' age than to specific
      diagnosis, type or duration of therapy.

PMID- 9152356
TI  - The effects of a series of volcanic eruptions on emotional and behavioural
      functioning in children with asthma.
AB  - AIMS: To determine whether children with asthma experienced disruptions in
      emotional and behavioural functioning following a series of volcanic eruptions.
      METHODS: Multitrait, multimethod assessment was carried out with children living
      in the volcanic area. Self reports, teacher reports, and parent reports were
      collected on 118 children and addressed issues related to psychiatric disruptions
      resulting from the eruptions. RESULTS: Asthma was reported by 30% of the sample
      and this figure compares favourably with previous findings with other New Zealand
      samples. These asthmatic children were compared with a group of nonasthmatic
      children on a range of psychiatric symptoms following the volcanic eruptions.
      Asthmatic children reported, and were observed by parents and teachers, to
      manifest greater levels of eruption related distress when compared to a group of
      nonasthmatic children. Children with asthma were found to have significantly
      higher symptom scores on several indices including those related to eruption
      related general distress and context-specific problems (eg, upset at home, upset
      when eruptions were discussed). Additionally, these children perceived their
      parents to be significantly more upset than the parents themselves reported. It
      is important to note that asthmatic children, while clearly more distressed, did
      not as a group evidence clinical levels of posttraumatic stress disorder
      symptomatology. CONCLUSIONS: Children with asthma were more psychologically
      vulnerable to the volcanic eruptions than children without asthma. These findings
      have implications for the behavioural management of asthma in children.
      Discussion integrates current findings with other recent data in highlighting the
      potential in supplementing traditional asthma management techniques.

PMID- 9152357
TI  - Pernicious anaemia patients should be screened for iron deficiency during follow
      up.
AB  - AIMS: To investigate if patients with pernicious anaemia (PA) are prone to
      develop iron deficiency and if there is a difference for this manifestation
      between younger and older age groups. METHODS: Ninety-five patients with
      pernicious anaemia were evaluated for body iron status at the time of diagnosis
      and during follow up. Patients were also divided into two groups; younger than 60
      (53 patients) and older than 60 (42 patients) years of age. Groups were compared
      for iron deficiency both at the time of diagnosis and at the end of follow up
      period. RESULTS: Iron deficiency was a common finding in patients with pernicious
      anaemia. This deficiency state was more common in the elderly. During B12
      therapy, iron deficiency increased in all groups, but the increased rate of iron
      deficiency was more prominent in the elderly patients. CONCLUSION: Pernicious
      anaemia is an atrophic gastropathy in which gastric parietal cells no longer
      produce hydrochloric acid. These patients with achlorhydria demonstrate impaired
      absorption of iron. On the other hand, with ageing, gastric acidity is already
      diminished. Iron deficiency commonly accompanies patients with pernicious anaemia
      and this is more pronounced in the elderly group. We suggest that all patients
      with pernicious anaemia, especially the elderly, should be screened for iron
      deficiency both at the beginning and during the follow up.

PMID- 9152358
TI  - Dr Samuel Matthias Curl alias Dr Alan Carroll.
AB  - Samuel Matthias Curl was the first medical practitioner in Tawa commencing
      practice there in 1855. He moved to the Rangitikei district in 1862 and practised
      there until 1887 when he eloped to Sydney with Annie Douglas. Besides practising
      medicine in New Zealand he farmed in both areas, was noted for his agricultural
      research and his work on several committees. In Sydney he assumed the name of Dr
      Alan Carroll and worked as an anthropologist and child health adviser. He died on
      the 17 April 1911 and left his estate in trust to establish two scientific
      bequests.

PMID- 9152359
TI  - Neonatal retrievals from homebirths.

PMID- 9152360
TI  - Neonatal retrievals from homebirths.

PMID- 9152361
TI  - Neonatal retrievals from homebirths.

PMID- 9152362
TI  - Drugs in sports medicine.

PMID- 9152363
TI  - Studies on the metabolic activation of disulfiram in rat. Evidence for
      electrophilic S-oxygenated metabolites as inhibitors of aldehyde dehydrogenase
      and precursors of urinary N-acetylcysteine conjugates.
AB  - Recent studies on the mechanism by which disulfiram inhibits aldehyde
      dehydrogenase have provided evidence for the formation of reactive intermediates
      that are thought to carbamoylate, and thereby inactivate the enzyme. In our
      study, rats were dosed with either disulfiram (0.25 mmol kg-1 i.p.) or its
      reduced metabolite diethyldithiocarbamate (DDTC; 0.5 mmol kg-1 i.p.) and urine
      was collected for the analysis of metabolites derived from putative reactive
      intermediates. By means of ionspray LC-MS/MS, two novel N-acetylcysteine (NAC)
      conjugates, i.e., N-acetyl-S-(N, N-diethylcarbamoyl)cysteine and N-acetyl-S-(N, N
      diethylthiocarbamoyl)cysteine, were identified in urine specimens. Quantitative
      analyses indicated that, over the 0- to 24-hr period after drug administration,
      urinary excretion of N-acetyl-S-(N, N-diethylcarbamoyl)cysteine accounted for 7.5
      +/- 4.0 and 6.2 +/- 1.0%, respectively, of the dose of disulfiram and
      diethyldithiocarbamate, while the corresponding thiocarbamoyl conjugate, N-acetyl
      S-(N, N-diethylthiocarbamoyl)cysteine, accounted for a further 0.5 +/- 0.3 and
      0.3 +/- 0.1%, respectively, of the dose. These conjugates are believed to derive
      from reactive sulfoxide and sulfone metabolites of disulfiram, namely S-methyl-N,
      N-diethylthiocarbamate sulfoxide (DETC-MeSO), S-methyl-N, N-diethylthiocarbamate
      sulfone (DETC-MeSO2), S-methyl-N, N-diethyldithiocarbamate sulfoxide (DDTC-MeSO)
      and S-methyl-N, N-diethyldithiocarbamate sulfone (DDTC-MeSO2), which were found
      to carbamoylate N-acetylcysteine in vitro with the following rank order of
      reactivity: DDTC-MeSO2 > DETC-MeSO2 > DDTC-MeSO > DETC-MeSO. In vitro experiments
      with aldehyde dehydrogenase showed that all four S-oxygenated metabolites
      inhibited the enzyme effectively. Furthermore, inclusion of NAC in incubation
      media attenuated significantly the inhibition by DDTC-MeSO2, DETC-MeSO2 and DDTC
      MeSO, but had little effect on that by DETC-MeSO. Our results are consistent with
      the hypothesis that disulfiram and diethyldithiocarbamate undergo activation by a
      sequence of metabolic reactions leading to the formation of electrophilic S
      methyl sulfoxides and sulfones that carbamoylate, and thereby inhibit, aldehyde
      dehydrogenase and possibly other enzymes.

PMID- 9152364
TI  - Effects of adrenergic, cholinergic and ganglionic blockade on acute depressor
      responses to metformin in spontaneously hypertensive rats.
AB  - Metformin lowers blood pressure in humans and in experimental animal models. To
      determine the mechanism of acute metformin-induced hypotension, we measured
      changes in mean arterial pressure (MAP) and heart rate (HR) during metformin
      alone (0, 10, 50, 100 mg/kg i.v.; n = 10) and during concomitant alpha adrenergic
      (phentolamine, 5 mg/kg; n = 5), beta adrenergic (propranolol, 3 mg/kg; n = 6),
      muscarinic (atropine, 200 micrograms/kg; n = 7), ganglionic (hexamethonium, 30
      mg/kg; n = 11), nitric oxide synthase (NG-methyl-L-arginine acetate salt, 15 mg/
      kg; n = 9) and combination ganglionic plus alpha adrenergic plus beta adrenergic
      (n = 6) blockade in spontaneously hypertensive rats (SHR). Responses to metformin
      alone were also assessed in normotensive Wistar-Kyoto rats (n = 6). In SHRs,
      metformin elicited depressor responses accompanied by tachycardia (100 mg/kg;
      delta MAP, -26 +/- 3 mm Hg; delta HR, +49 +/- 12 bpm). Depressor responses in
      Wistar-Kyoto rats were significantly attenuated (100 mg/kg; delta MAP, -9 +/- 4
      mm Hg; P < .01). Hypotensive actions of metformin in SHRs were abolished and
      reversed into pressor responses by hexamethonium (100 mg/kg; delta MAP, +24 +/- 6
      mm Hg), phentolamine (100 mg/kg; delta MAP, +62 +/- 10 mm Hg) and by combination
      ganglionic plus adrenergic (100 mg/kg; delta MAP, +62 +/- 10 mm Hg) blockade.
      Neither propranolol, atropine nor NG-methyl-L-arginine acetate salt affected
      hypotensive responses to metformin. We conclude that acute intravenous metformin
      administration decreases MAP by causing withdrawal of sympathetic activity. The
      increase in MAP uncovered by hexamethonium and phentolamine suggests that the
      original depressor response to metformin is buffered by mechanisms unrelated to
      the autonomic nervous system.

PMID- 9152365
TI  - Losartan, a selective inhibitor of subtype AT1 receptors for angiotensin II,
      inhibits the binding of N-formylmethionyl-leucyl-phenylalanine to neutrophil
      receptors.
AB  - Losartan, a selective antagonist of AT1 receptors for angiotensin II, is widely
      used clinically to manage hypertension. We report here that losartan markedly
      inhibits neutrophil shape change, adherence and chemiluminescence responses
      triggered by N-formylmethionyl-leucyl-phenylalanine (fMLP), without affecting
      responses induced by immune complexes, zymosan or concanavalin A. Neither
      saralasin, another antagonist of angiotensin II receptors, nor captopril, an
      angiotensin-converting enzyme inhibitor, reproduced the effects of losartan. It
      was also observed that neutrophil responses triggered by fMLP were not affected
      by exogenously added angiotensin II. The effect of losartan on the binding of
      fMLP was measured using [3H]fMLP. It was found that losartan inhibits the binding
      of [3H]fMLP to neutrophil receptors. As observed for neutrophils, studies
      performed with monocytes showed that losartan inhibits chemiluminescence emission
      triggered by fMLP, without affecting chemiluminescence responses triggered by
      immune complexes, zymosan or concanavalin A.

PMID- 9152366
TI  - Novel cyclic peptide agonist of high potency and selectivity for the type II
      vasoactive intestinal peptide receptor.
AB  - Ro 25-1392 [Ac-Glu8,OCH3-Tyr10,Lys12,Nle17,Ala19,A sp25,Leu26,-Lys27,28
      vasoactive intestinal peptide(cyclo 21-25)] is a cyclic peptide analog of
      vasoactive intestinal peptide (VIP) that potently exerts cellular effects typical
      of VIP. The selectivity of Ro 25-1392 for type I (VIPR1) and type II (VIPR2) VIP
      receptors was investigated first in competitive binding studies using Chinese
      hamster ovary cell transfectants stably expressing recombinant human VIPR1 and
      VIPR2. Nonradioactive Ro 25-1392 was as potent a competitive inhibitor as VIP for
      the binding of 125I-VIP to VIPR2 transfectants (Ki = 9.6 +/- 1.0 and 16 +/- 1.7
      nM, respectively; mean +/- S.E.M., n = 4). In contrast, Ro 25-1392 had a very low
      affinity for VIPR1, compared with VIP, and attained a maximum of only 40% mean
      inhibition of binding of 125I-VIP at 1 microM. The affinity of VIP (Ki = 3.4 +/-
      1.5 nM, mean +/- S.E.M., n = 4) for binding to VIPR1 was 1000-fold greater than
      that of Ro 25-1392. Ro 25-1392 evoked concurrent and concentration-dependent
      increases in intracellular levels of calcium and cyclic AMP (EC50 = 3.0 +/- 0.4
      nM, mean +/- S.E.M., n = 4) in VIPR2 transfectants, but not in VIPR1
      transfectants. The VIP receptor specificity of Ro 25-1392 was confirmed by
      preincubation of Chinese hamster ovary transfectants with 0.1 microM Ro 25-1392
      for 18 hr at 37 degrees C, to down-regulate each type of VIP receptor.
      Pretreatment of VIPR2 transfectants with Ro 25-1392 decreased Bmax by a mean of
      58% and VIP-induced increases in the intracellular concentration of cyclic AMP by
      a mean of 65%. In contrast, there was no significant change in VIPR1
      transfectants after pretreatment with Ro 25-1392. Ro 25-1392 thus is selectively
      recognized by VIPR2, with consequent initiation of cyclic AMP and Ca+2 signals
      and down-regulation of VIPR2. This potent analog of VIP may prove useful for
      investigations of VIPR2-mediated physiological effects of VIP and exploration of
      the roles of VIPR2 in diseases.

PMID- 9152367
TI  - Vasodilator action of calcium antagonists in coronary arteries in vitro.
AB  - Calcium antagonists have routinely been assumed to inhibit the contractions of
      arterial smooth muscle through block of membrane channels. The effects of
      nifedipine and diltiazem on contractions were examined in in vitro preparations
      of cattle coronary artery, one of the key therapeutic targets of calcium
      antagonists, to determine if alternate mechanisms of action are involved.
      Contractions elicited in calcium-free Krebs, in the presence of U 46619, to
      potassium channel inhibitors (4-aminopyridine and tetraethylammonium) and to a
      Na(+)-K(+)-ATPase inhibitor (ouabain), were antagonized by low concentrations of
      nifedipine (3 x 10(-9)-3 x 10(-8) M) and by diltiazem (3 x 10(-8) and 1 x 10(-7)
      M). Contractions produced in calcium-free Krebs to KCl (50 mM) were antagonized
      similarly by calcium antagonists. Contractions to depolarizing agents in calcium
      free Krebs were antagonized at lower concentrations of nifedipine than comparably
      elicited responses in Krebs containing 2.3 mM calcium. In addition, higher
      concentrations of nifedipine were required to antagonize contractions to
      extracellular calcium, produced in preparations maintained in calcium-free Krebs
      in the presence of KCl (50 mM), than were needed to block contractions to KCl or
      to potassium channel inhibitors elicited in calcium-free Krebs. Pretreatment of
      preparations in calcium-free Krebs with ryanodine (30 microM) did not reduce the
      nifedipine-sensitive contractions elicited in calcium-free Krebs. It is concluded
      that at least some of the therapeutic effects of calcium antagonists on arterial
      tone may be the consequence of antagonism at vascular smooth muscle cell site(s)
      at which calcium is released or interacts, rather than of block of calcium entry
      through membrane L channels.

PMID- 9152368
TI  - Activation of the metabotropic glutamate receptor mGluR5 prevents glutamate
      toxicity in primary cultures of cerebellar neurons.
AB  - 1-Aminocyclopentane-trans-1,3-dicarboxylic acid, an agonist of the metabotropic
      glutamate receptors 1, 2, 3 and 5, prevents neurotoxicity of glutamate and of N
      methyl-D-aspartate in primary cultures of cerebellar neurons. The aim of this
      work was to assess which of the metabotropic glutamate receptors (mGluRs) is
      responsible for the protective effect. We tested the protective effects of
      selective agonists for each type of receptor. It is shown that glutamate and N
      methyl-D-aspartate neurotoxicity are prevented by the following compounds: 1
      amino-cyclo-pentane-trans-1,3-dicarboxylic acid, agonist of mGluR1, 2, 3 and 5;
      3,5-dihydroxyphenylglycine, agonist of mGluR1 and 5; S-4-carboxy-3
      hydroxyphenylglycine, agonist of mGluR5 and antagonist of mGluR1; trans-azetidine
      2,4-dicarboxylic acid, agonist of mGluR5. Glutamate neurotoxicity is not
      prevented by (2S,1'S,2'S)-2(2'-carboxycyclopropyl)glycine, an agonist of mGluR2
      and mGluR3. Moreover, the protective effect of 1-aminocyclo-pentane-trans-1,3
      dicarboxylic acid is prevented by alpha-methyl-4-carboxyphenylglycine, an
      antagonist of mGluR1 and 5, but not by alpha-methyl-4-tetrazoylphenylglycine, an
      antagonist of mGluR2 and 3. A protective effect of activation of mGluR1 can not
      be ruled out because of the limitations imposed by the lack of specificity of the
      agonists and antagonists currently available. The results shown clearly indicate
      that activation of mGluR5 prevents glutamate and N-methyl-D-aspartate
      neurotoxicity in primary cultures of cerebellar neurons.

PMID- 9152369
TI  - Hippocampal noradrenaline release in awake, freely moving rats is regulated by
      alpha-2 adrenoceptors but not by adenosine receptors.
AB  - In this study, the ability of the nonselective adenosine receptor antagonist
      caffeine to influence the concentration of noradrenaline in the central nervous
      system was investigated, and its effects compared with those of alpha-2
      adrenoceptor modulation. The technique of microdialysis in association with
      microbore high-performance liquid chromatography and electrochemical detection
      was used to measure the extracellular concentrations of noradrenaline in the
      hippocampus of awake, freely moving rats. Neither the oral administration of
      caffeine nor its local perfusion influenced the base-line hippocampal levels of
      noradrenaline. Furthermore, the levels of noradrenaline were not influenced by
      local perfusion of the selective adenosine A1 agonist N6-cyclopentyladenosine or
      by the selective adenosine A2 agonist CGS 21680. In contrast, the extracellular
      levels of noradrenaline could be increased by the perfusion of the selective
      alpha-2 adrenoceptor antagonist idazoxan and decreased by local perfusion of
      Ca(+2)-free phosphate buffered saline, a Na(+)-channel blocker, tetrodotoxin, or
      the selective alpha 2-adrenoceptor agonist clonidine. The extracellular levels of
      noradrenaline were stimulated by the local perfusion of different concentrations
      of K+ (10-100 mmol/l). The K(+)-dependent increase in the extracellular levels of
      noradrenaline was potentiated by local perfusion of idazoxan and inhibited by
      local perfusion of clonidine. In contrast, neither the oral administration of
      caffeine nor its local perfusion influenced the K(+)-stimulated increases in
      hippocampal noradrenaline. Furthermore, local perfusion of N6
      cyclopentyladenosine or CGS 21680 did not influence the K(+)-stimulated levels of
      noradrenaline either. These results indicate that base-line and K(+)-stimulated
      extracellular levels of noradrenaline in the hippocampus of awake, freely moving
      rats are regulated by alpha-2 adrenoceptors and not by adenosine receptors.

PMID- 9152370
TI  - Cysteinyl leukotrienes induce P-selectin expression in human endothelial cells
      via a non-CysLT1 receptor-mediated mechanism.
AB  - Cysteinyl leukotrienes are bioactive lipid mediators known to possess potent
      proinflammatory actions. Included in these are effects on vascular endothelium to
      promote surface expression of the adhesion molecule P-selectin. In the present
      study we were interested in investigating the receptor mechanism(s) involved in
      cysteinyl leukotriene-induced endothelial P-selectin expression. As such we
      examined the effect of several potent and selective cysteinyl leukotriene
      receptor antagonists on this response. Incubation of cultured human umbilical
      vein endothelial cells (HUVEC) with the cysteinyl leukotrienes leukotriene C4
      (LTC4) or leukotriene D4 (LTD4) induced surface expression of P-selectin which
      was concentration dependent and rapid in onset. Expression of endothelial P
      selectin induced by either LTC4 or LTD4 was not blocked however by pretreatment
      of HUVEC with the selective cysteinyl leukotriene-1 (CysLT1) receptor antagonists
      SKF 104353, pranlukast or zafirlukast before agonist exposure. In contrast, SKF
      104353 effectively antagonized the LTC4-induced contractions in isolated human
      bronchial smooth muscle preparations, shifting the agonist dose-response curve to
      the right by some 3 log-fold in this tissue. The present results suggest that
      cysteinyl leukotrienes induce surface expression of endothelial P-selectin via a
      mechanism independent of the CysLT1 receptor.

PMID- 9152371
TI  - A peptidomimetic that specifically inhibits human leukocyte antigen DRB1*0401
      restricted T cell proliferation.
AB  - The ability of a peptidomimetic (SC-67655) to block the peptide binding site of
      the rheumatoid arthritis-linked human leukocyte antigen encoded by the DRB1*0401
      allele was evaluated. The inhibitor bound to purified DRB1*0401 molecules with an
      affinity similar to that of the well-characterized peptide ligand HA307-319. Cell
      binding assays demonstrated that, in contrast to the promiscuous HA307-319
      peptide, the peptidomimetic was highly specific for DRB1*0401. The inhibitor also
      blocked functional T cell responses to peptide antigens but did not block T cell
      proliferation in response to protein antigens. Furthermore, it did not appear to
      be taken up by cells. An analog of the peptidomimetic that was conjugated to a
      signal peptide sequence did inhibit a T cell proliferative response to protein
      antigen. Thus, the peptidomimetic must be taken up by cells to block the
      presentation of peptides derived from protein antigens. These findings have
      implications for the rational development of inhibitors that block the class II
      peptide binding groove for the treatment of autoimmune diseases.

PMID- 9152372
TI  - The peripheral action of clonidine analog ST-91: involvement of atrial
      natriuretic factor.
AB  - It is generally thought that the cardiovascular and renal effects of clonidine,
      an alpha-2 adrenergic agonist, are mediated by central mechanisms. Our previous
      work has shown that diuresis and natriuresis caused by central administration of
      clonidine are mediated by an enhanced release of atrial natriuretic factor (ANF).
      Because clonidine has been shown to have peripheral actions the objective of the
      present study was to determine whether ANF is also involved in these actions.
      Studies were performed with use of a structural clonidine analog, ST-91, which
      does not cross the blood-brain barrier, Intravenous injection of various doses (0
      250 micrograms/rat) of ST-91 into conscious, normally hydrated female Sprague
      Dawley rats (200-250 g) produced dose-related increases in urinary output, which
      were accompanied by significant increases in urinary sodium, potassium and cGMP
      excretion. Compared with saline, the highest dose of ST-91 (250 micrograms/rat)
      during the first hour of treatment significantly (P < .001, n = 18) enhanced
      urinary output (0.2 +/- 0.1 vs. 3.0 +/- 1.1 ml/h) and excretion of sodium (28 +/-
      4 vs. 345 +/- 50 mumol/h), potassium (10 +/- 4 vs. 165 +/- 37 mumol/h) and cGMP
      (191 +/- 29 vs. 1340 +/- 322 pmol/h), the biological marker of ANF. These renal
      responses were associated with increased plasma ANF (59 +/- 7 vs. 810 +/- 28
      pg/ml, P < .001, n = 12), measured 10 min after ST-91 (250 micrograms/rat), which
      remained elevated for at least 1 h (P < .01, n = 6). The enhanced renal responses
      that were induced by 10 micrograms ST-91 were partially, yet significantly
      inhibited by yohimbine (50 micrograms), an alpha-2 antagonist. On the other hand,
      efaroxan (500 micrograms), an l1 imidazoline receptor antagonist, showed a
      stronger inhibitory effect, whereas naloxone (0.8 mg) had no effect. Pretreatment
      of rats with anti-ANF reduced the diuretic and natriuretic effects of ST-91.
      These results indicate that the renal effects of ST-91 are mediated by
      imidazoline as well as by alpha-2 adrenergic receptors, but not by opioid
      receptors. Furthermore, the renal effects evoked by ST-91 are mediated by ANF.

PMID- 9152373
TI  - Nonpeptide glycoprotein IIb/IIIa inhibitors. 15. Antithrombotic efficacy of L
      738,167, a long-acting GPIIb/IIIa antagonist, correlates with inhibition of
      adenosine diphosphate-induced platelet aggregation but not with bleeding time
      prolongation.
AB  - The nonpeptide platelet glycoprotein IIb/IIIa antagonist, L-738, 167, was
      characterized in dog and nonhuman primate. In an anesthetized canine model of
      coronary artery electrolytic lesion, L-738,167 elicited dose-dependent (3, 4, 4.5
      and 5 micrograms/kg i.v.) decreases in incidence of occlusion, reductions in
      thrombus mass and elevations in bleeding time. Antithrombotic efficacy correlated
      with inhibition of adenosine diphosphate-induced platelet aggregation but was
      dissociated from marked bleeding time elevation. Similarly, suppression of
      platelet-dependent cyclic flow reductions with L-738,167 in the canine coronary
      artery (5 micrograms/kg i.v.) and African green monkey carotid artery (10
      micrograms/kg i.v.) correlated with inhibition of adenosine diphosphate-induced
      platelet aggregation but not with inhibition of thrombin-induced platelet
      aggregation or significant prolongation of bleeding time. In conscious dogs and
      sedated chimpanzees, single dose intravenous bolus (5-20 micrograms/kg) and oral
      (25-200 micrograms/kg) administration of L-738,167 exhibited long duration (> or
      = 8 hr) inhibition of ex vivo platelet aggregation. Once daily oral
      administration to conscious dogs (10-30 micrograms/kg/day for 15 days) and rhesus
      monkeys (200-250 micrograms/kg/day for 11 days) maintained significant but
      submaximal (50-90% inhibition) trough levels of inhibition of adenosine
      diphosphate-induced ex vivo platelet aggregation. Platelet sensitivity to
      adenosine diphosphate after multiple days of oral dosing in dogs was similar to
      pretreatment sensitivity. L-738,167 showed characteristics suitable for chronic
      oral therapy with a glycoprotein IIb/IIIa inhibitor.

PMID- 9152374
TI  - Receptor reserve and turnover of alpha-2 adrenoceptors that mediate the clonidine
      induced inhibition of rat locus coeruleus neurons in vivo.
AB  - The population of reserve alpha-2 adrenoceptors that mediate the inhibitory
      effect of clonidine on the activity of locus coeruleus neurons has been studied
      using extracellular recordings in anesthetized rats. Animals were pretreated with
      the irreversible receptor antagonist N-ethoxycarbonyl-2-ethoxy-1-2
      dihydroquinoline (EEDQ). In rats pretreated with EEDQ (1, 2 and 6 mg/kg, i.p., 6
      hr before experiment), there was an increase in firing rate, a reduction in
      firing regularity (i.e., increased variation coefficient) and an increase in
      burst firing of locus coeruleus neurons. Partial receptor inactivation with EEDQ
      (1 and 2 mg/kg, i.p.) caused a dose-dependent shift to the right of dose-effect
      curves for i.v. administered clonidine together with a reduction in its maximal
      effect. Higher doses of EEDQ (6 mg/kg, i.p.) completely abolished the effect
      induced by clonidine. This blockade was associated with a progressive decrease in
      the number of remaining receptors (noninactivated receptors). The pseudo-constant
      of dissociation for the drug-receptor complex was calculated to be approximately
      70 micrograms/kg. The receptor occupancy-effect relationship was hyperbolic
      giving a value of only approximately 4% occupancy at 50% maximal effect.
      Estimates of noninactivated receptors and percentage of receptor occupancy at 50%
      of maximal effect were comparable when locally administered clonidine was used.
      After complete receptor inactivation with EEDQ (6 mg/kg), dose-effect curves for
      clonidine recovered gradually. The inhibitory effect of clonidine returned faster
      (half-life = 14 hr) than the receptor pool (half-life = 37 hr). These results
      indicate that locus coeruleus neurons have a large reserve of alpha 2
      adrenoceptors that in addition, are rapidly turned over.

PMID- 9152375
TI  - Increased responsiveness of ventral tegmental area dopamine neurons to glutamate
      after repeated administration of cocaine or amphetamine is transient and
      selectively involves AMPA receptors.
AB  - It is well established that behavioral sensitization to psychomotor stimulants is
      associated with adaptations in the mesoaccumbens dopamine (DA) system. We showed
      previously that the responsiveness of ventral tegmental area (VTA) DA neurons to
      glutamate was significantly enhanced in amphetamine- and cocaine-pretreated rats
      tested after 3 days of withdrawal, which suggests that adaptations in excitatory
      amino acid transmission also contribute to sensitization. The purpose of the
      present study was to determine the subtype of excitatory amino acid receptor
      responsible for this effect and to examine its persistence during withdrawal.
      Extracellular single cell recording and microiontophoresis were used to
      investigate possible alterations in the ability of glutamate agonists [(S)-alpha
      amino-3- hydroxy-5-methyl-4-isoxazole propionate (AMPA), N-methyl-D-aspartate
      (NMDA), and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-t-ACPD)] to
      stimulate the firing of VTA DA neurons after 3 days of withdrawal from repeated
      administration of saline, cocaine or amphetamine. Current-response curves showed
      that responses to iontophoretic AMPA, but not NMDA or 1S,3R-t-ACPD were
      significantly enhanced in cocaine- or amphetamine-pretreated rats in that neurons
      entered into a state of apparent depolarization block at significantly lower
      iontophoretic currents. When rats were tested for responsiveness to iontophoretic
      glutamate after 14 days of withdrawal, there was no significant difference
      between cocaine- or amphetamine- and saline-pretreated rats with respect to
      glutamate current-response curves. These results suggest that increased
      responsiveness of AMPA receptors on VTA DA neurons may contribute to
      sensitization at early withdrawal times, but that this alteration, like others
      described within the VTA, is transient.

PMID- 9152376
TI  - Mechanism of attenuation of morphine antinociception by chronic treatment with L
      arginine.
AB  - The effects of twice-daily injections of L-arginine or D-arginine (200 mg/kg
      i.p.) for 4 days on morphine-induced antinociception, brain nitric oxide synthase
      activity and brain and serum distribution of morphine and brain mu-opioid
      receptors labeled with [3H][D-Ala2,MePhe4,Gly5-ol]enkephalin were determined in
      male Swiss-Webster mice. Chronic treatment with L-arginine, but not D-arginine,
      decreased the antinociceptive response to morphine in mice, increased the
      activity of nitric oxide synthase in the midbrain and decreased brain levels of
      morphine, compared with vehicle-injected controls. Significant decreases in
      morphine levels were observed in midbrain, pons and medulla, hippocampus,
      striatum and spinal cord of L-arginine-treated mice, in comparison with vehicle
      injected mice. However, the levels of morphine in cortex, amygdala and
      hypothalamus of L-arginine- or D-arginine-treated mice did not differ from those
      of vehicle-injected controls. Acute treatment with L-arginine (200 mg/kg i.p.) or
      D-arginine (200 mg/kg i.p.) did not modify either morphine antinociception or
      morphine distribution in brain regions or the spinal cord. Chronic administration
      of L-arginine or D-arginine did not alter the Bmax or Kd values of [3H][D
      Ala2,MePhe4,Gly5-ol]enkephalin binding to the mouse brain membranes. These
      results suggest that chronic treatment with L-arginine reduces the
      antinociceptive effect of morphine by increasing brain nitric oxide synthase
      activity and by decreasing the concentration of morphine in certain brain regions
      and spinal cord.

PMID- 9152377
TI  - Pharmacodynamics and tolerance development during multiple intravenous bolus
      morphine administration in rats.
AB  - Limited information is available about how the time course of the development of
      tolerance to morphine-induced antinociception is related to the kinetics of drug
      administration and disposition. The objectives of the present experiment were to
      characterize the rate and extent of tolerance development during the
      administration of multiple increasing i.v. bolus doses of morphine to rats, and
      to construct a pharmacokinetic-pharmacodynamic model of morphine tolerance.
      Morphine was administered according to two different treatment (TXT) regimens: a
      12-hr TXT, in which a total morphine exposure of 24 mg/kg was administered in
      seven escalating doses, and a 13-day TXT, in which escalating doses of morphine
      were administered daily up to a maximum of 6 mg/kg. Analgesic effect, expressed
      as the percent of maximum possible response, was assessed with the hot water
      induced tail flick. Serum samples were collected for determination of morphine
      concentrations by HPLC. Concentration-normalized peak effects, measured after
      each morphine dose, remained constant throughout the 12-hr study period, which
      suggests that there was little or no tolerance development during the 12-hr TXT.
      In contrast, tolerance appeared more significant during administration of the 13
      day TXT; a large decrease in normalized peak effect occurred between days 1 and
      8. Effect remained constant thereafter, with administration of the maximum dose
      of morphine for the remainder of the treatment period. A pharmacokinetic
      pharmacodynamic model describing the development of tolerance during the 13-day
      TXT was constructed. The applicability of this model of tolerance to morphine
      induced antinociception with different modes of administration is discussed.

PMID- 9152378
TI  - Pharmacological characterization of 1-aminoindan-1,5-dicarboxylic acid, a potent
      mGluR1 antagonist.
AB  - We examined the pharmacological profile of 1-aminoindan-1,5-dicarboxylic acid
      (AIDA), a rigid (carboxyphenyl)glycine derivative acting on metabotropic
      glutamate receptors (mGluRs). In cells transfected with mGluR1a, AIDA
      competitively antagonized the stimulatory responses of glutamate and (1S,3R)-1
      aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD] on phosphoinositide
      hydrolysis (pA2 = 4.21). In cells transfected with mGluR5a, AIDA displayed a much
      weaker antagonist effect. In transfected cells expressing mGluR2, AIDA (< or = 1
      mM) did not affect the inhibition of forskolin-stimulated adenylate cyclase
      activity induced by (1S,3R)-ACPD, but at large concentrations, it displayed a
      modest agonist activity. In rat hippocampal or striatal slices, AIDA (0.1-1 mM)
      reduced the effects of (1S,3R)-ACPD on phospholipase C but not on adenylate
      cyclase responses, whereas (+)-alpha-methyl-4-carboxyphenylglycine (0.3-1 mM) was
      an antagonist on both transduction systems. In addition, AIDA (0.3-1 mM) had no
      effect on mGluRs coupled to phospholipase D, whereas (+)-alpha-methyl-4-carboxy
      phenylglycine (0.5-1 mM) acted as an agonist with low intrinsic activity. In rat
      cortical slices, AIDA antagonized the stimulatory (mGluR1-mediated) effect of
      (1S,3R)-ACPD on the depolarization-induced outflow of D-[3H]aspartate, disclosing
      an inhibitory effect ascribable to (1S,3R)-ACPD activating mGluR2 and/or mGluR4.
      Finally, mice treated with AIDA (0.1-10 nmol i.c.v.) had an increased pain
      threshold and difficulties in initiating a normal ambulatory behavior. Taken
      together, these data suggest that AIDA is a potent, selective and competitive
      mGluR1 a antagonist.

PMID- 9152379
TI  - Involvement of dynorphin B in the antinociceptive effects of the cannabinoid
      CP55,940 in the spinal cord.
AB  - Intrathecal administration of delta 9-tetrahydrocannabinol (delta 9-THC) but not
      the cannabinoid agonist CP55,940 enhances the antinociception produced by
      morphine. In addition, CP55,940- and delta 9-THC-induced antinociception is
      blocked by the kappa opioid antagonist norbinaltorphimine, and both cannabinoids
      are cross-tolerant to kappa agonists but do not act directly at the kappa
      receptor. Previous work in our laboratory has implicated dynorphins in the
      antinociceptive effects of delta 9-THC and its enhancement of morphine-induced
      antinociception. The goal of the present study was to evaluate the role of
      dynorphins in the antinociceptive effects of CP55,940 at the spinal level.
      Pretreatment of mice with antisera to dynorphin A(1-17), dynorphin A(1-8) or
      alpha-neoendorphin, all of which have been shown to retain specificity for
      blockade of their respective peptide in vivo, blocked the antinociceptive effects
      of delta 9-THC but not CP55,940. Dynorphin B produced antinociceptive effects on
      intrathecal administration to mice. Like CP55,940, dynorphin B failed to enhance
      the antinociceptive effects of morphine, whereas dynorphin A(1-17) and alpha
      neoendorphin enhanced the antinociceptive effects of morphine. Using spinal
      catheterization of the rat, CP55,940 administration was shown to produce a
      significant release of dynorphin B concurrent with the production of
      antinociception. Our data suggest that CP55,940 induces a release of spinal
      dynorphin B that contributes at least in part to its antinociceptive effects in
      the spinal cord.

PMID- 9152380
TI  - Increased intestinal absorption of cefixime by nifedipine in the rat intestinal
      perfusion model: evidence for a neural regulation.
AB  - In healthy volunteers, the simultaneous administration of nifedipine and cefixime
      has been shown to increase the oral absorption of the antibiotic. To investigate
      the pharmacological basis of this interaction, we used an in situ intestinal
      perfusion technique in the rat. pH 5.5 yielded optimum cefixime absorption, which
      was greater in segments from the duodenojejunum than in those from the
      jejunoileum. Cefixime absorption was similar when perfused at 0.5 and 1.0 mg/ml,
      suggesting transport saturation at the lower concentration. Cefixime arterial and
      portal blood concentrations after an intestinal perfusion of 0.5 mg/ml cefixime
      were significantly increased by a previous 15-min intestinal perfusion of 0.05
      mg/ml nifedipine. Nifedipine did not significantly alter intestinal blood flow.
      At the end of the cefixime perfusion, intestinal blood flow was higher in the
      nifedipine group than in the control group (0.44 +/- 0.12 vs. 0.26 +/- 0.09
      ml.min-1.g of intestine wt-1, respectively), although the difference did not
      reach statistical significance. The absorption kinetics of salicylic acid, which
      is strictly absorbed by passive diffusion, were unaffected by nifedipine. After
      15 and 50 min of recirculation, residual salicylate levels fell from 85.1 +/-
      5.6% to 57.1 +/- 2.8% with nifedipine compared with 87.4 +/- 1.4% to 52.8 +/-
      1.6% without nifedipine. Thus, the improvement in cefixime absorption by
      nifedipine was not secondary to increased local blood flows or to induced passive
      diffusion mechanisms. Nifedipine did not affect intestinal motility. The action
      of nifedipine appears to indirect, involving a neural regulation, because any
      increase in cefixime absorption was prevented by tetrodotoxin and hexamethonium
      administration.

PMID- 9152381
TI  - RPR 107393, a potent squalene synthase inhibitor and orally effective cholesterol
      lowering agent: comparison with inhibitors of HMG-CoA reductase.
AB  - Squalene synthase catalyzes the reductive dimerization of two molecules of
      farnesyl pyrophosphate to form squalene and is the first committed step in sterol
      synthesis. A specific inhibitor of squalene synthase would inhibit cholesterol
      biosynthesis but not prevent the formation of other products of the isoprenoid
      pathway, such as dolichol and ubiquinone. RPR 107393 [3-hydroxy-3-[4-(quinolin-6
      yl)phenyl]-1-azabicyclo[2-2-2]octane dihydrochloride] and its R and S enantiomers
      are potent inhibitors of rat liver microsomal squalene synthase, with IC50 values
      of 0.6 to 0.9 nM. One hour after oral administration to rats, RPR 107393
      inhibited de novo [14C]cholesterol biosynthesis from [14C]mevalonate in the liver
      with an ED50 value of 5 mg/kg. Diacid metabolites of [14C]farnesyl pyrophosphate
      were identified after acid treatment of the livers of these animals. These
      results support in vitro data demonstrating that these compounds are inhibitors
      of squalene synthase. In rats, RPR 107393 (30 mg/kg p.o. b.i.d. for 2 days)
      reduced total serum cholesterol by < or = 51%. In the same paradigm, the HMG-CoA
      reductase inhibitor lovastatin failed to lower serum cholesterol in rats. In
      marmosets, RPR 107393 (20 mg/kg b.i.d.) reduced plasma cholesterol concentration
      by 50% after 1 week of administration; this was greater than the reduction
      observed with lovastatin or pravastatin, neither of which produced > 31%
      reduction in plasma cholesterol when administered for 1 week at a dose of 50
      mg/kg b.i.d. The R and S enantiomers of RPR 107393 (20 mg/kg p.o. q.d. for 7
      days) reduced plasma low density lipoprotein cholesterol by 50% and 43%,
      respectively, whereas high density lipoprotein cholesterol was unchanged. In
      summary, RPR 107393 is a potent inhibitor of squalene synthase. It is an orally
      effective hypocholesterolemic agent in rats and marmosets that has greater
      efficacy than lovastatin or pravastatin in the marmoset.

PMID- 9152382
TI  - gamma-Hydroxybutyrate conversion into GABA induces displacement of GABAB binding
      that is blocked by valproate and ethosuximide.
AB  - gamma-Hydroxybutyrate (GHB) has been reported to be a ligand for GABAB
      receptor(s), although with low or very low affinity (IC50 = 150-796 microM). In
      addition, several reports argue for a role of GHB via GABAB receptors in both in
      vivo and in vitro electro-physiological experiments. In the present study, we
      demonstrate that the inhibition of GHB's conversion into GABA by rat brain
      membranes blocks the ability of GHB to interfere with GABAB binding. In
      particular, the inhibition of GHB dehydrogenase by valproate or ethosuximide and
      the blockade of GABA-T by aminooxyacetic acid induce the disappearance of the
      GABA-like effect of GHB at GABAB, but also at GABAA, receptors. This finding
      could explain the misinterpretation of in vitro or in vivo experiments where GHB
      possesses a GABA-like effect. But in addition, it is postulated that the normal
      metabolism of GHB in brain induces GABAB mechanisms that could be blocked by the
      administration of valproate or ethosuximide.

PMID- 9152383
TI  - Agonist-independent effect of an allosteric enhancer of the A1 adenosine receptor
      in CHO cells stably expressing the recombinant human A1 receptor.
AB  - The allosteric enhancer PD 81,723, a 2-amino-3-benzoylthiophene derivative, has
      been shown to potentiate agonist binding to A1 adenosine receptors (A1AdoRs) and
      to enhance the functional effects of adenosine and adenosine analogs. The
      objective of this study was to determine whether the apparent agonist-independent
      effect of PD 81,723 observed in CHO cells stably expressing the recombinant human
      A1AdoR was due to the potentiation of the action of endogenous adenosine, to the
      presence of constitutive receptor activity and/or to the binding of PD 81,723 to
      the agonist binding site of the A1AdoR. The allosteric enhancer PD 81,723, the
      A1AdoR agonist (R)-N6-(2-phenylisopropyl)adenosine and adenosine all
      significantly inhibited forskolin-stimulated cAMP accumulation in intact cells
      and increased [35S]-5'-(gamma-thio)triphosphate binding to cell membranes. The
      effects of adenosine on cAMP formation and [35S]-5'-(gamma-thio)triphosphate
      binding were attenuated by adenosine deaminase, but the effects of PD 81,723 were
      not. In the presence of ADA, the A1AdoR antagonist 8-cyclopentyl-1,3
      dipropylxanthine increased forskolin-stimulated cAMP accumulation in cells
      expressing the recombinant human A1AdoR but not in nontransfected CHO cells. In
      binding experiments, the agonist (R)-N6-(2-phenylisopropyl)adenosine, but not PD
      81,723, significantly displaced the specific binding of the A1AdoR agonist [3H]
      N6-cyclohexyladenosine and the antagonist [3H]-8-cyclopentyl-1,3
      dipropylxanthine. The results of this study demonstrate that in CHO cells stably
      expressing the recombinant human A1AdoR, the agonist-independent effect of PD
      81,723 is not due to potentiation of the action of endogenous adenosine or
      mediated by the binding of the allosteric enhancer to the agonist binding site of
      the recombinant human A1AdoR. It is possible that these effects are due to
      potentiation of constitutive receptor activity by PD 81,723.

PMID- 9152384
TI  - Almost complete protection from [Met5]-enkephalin-Arg6-Gly7-Leu8 (Met-enk-RGL)
      hydrolysis in membrane preparations by the combination of amastatin, captopril
      and phosphoramidon.
AB  - The contents of [Met5]-enkephalin-Arg6-Gly7-Leu8 (met-enk-RGL) and its seven
      hydrolysis products-Y, YG, YGG, YGGF, YGGFM, YGGFMR, and YGGFMRG-were estimated
      after incubating met-enk-RGL with a membrane fraction from either guinea pig
      ileum or striatum for various times at 37 degrees C. After 15 min of incubation,
      met-enk-RGL was completely hydrolyzed in both the ileal and the striatal membrane
      preparations. The major hydrolysis products were YGGFMR, YGGF and Y, which
      indicates that dipeptidyl carboxypeptidase and aminopeptidase activities were
      mainly involved in the hydrolysis. Additionally, even when the ileal and the
      striatal preparations were incubated for 60 min in the presence of both
      captopril, a dipeptidyl carboxypeptidase inhibitor, and amastatin, an
      aminopeptidase inhibitor, 24% and 44% of enkephalin octapeptide, respectively,
      were hydrolyzed. The YGG fragment was the major hydrolysis product in both
      preparations. When the ileal and the striatal membrane fractions were incubated
      with met-enk-RGL in the presence of three peptidase inhibitors-captopril,
      amastatin, and phosphoramidon (an inhibitor of endopeptidase-24.11)-approximately
      95% of the enkephalin octapeptide, remained intact in both cases. This shows that
      met-enk-RGL was almost exclusively hydrolyzed by three enzymes, amastatin
      sensitive aminopeptidase, captopril-sensitive dipeptidyl carboxypeptidase I and
      phosphoramidon-sensitive endopeptidase-24.11, in both ileal and striatal
      membranes. We also reported the potencies of several opioids relative to that of
      met-enk-RGL in guinea pig ileum pretreated with the three peptidase inhibitors.

PMID- 9152385
TI  - Central serotonergic systems in the spontaneously hypertensive and Lewis rat
      strains that differ in the elevated plus-maze test of anxiety.
AB  - The spontaneously hypertensive (SHR) and Lewis (LEW) strains differ in numerous
      behavioral tests, including the elevated plus-maze. In keeping with the crucial
      role of central serotonin (5-HT) in anxiety, we checked for strain differences
      regarding several determinants of 5-HT activity. In addition to confirming that
      LEW rats displayed anxious behaviors in the plus-maze compared with SHR, we found
      that in vitro, central tryptophan hydroxylase activity was higher in LEW rats
      than in SHR. However, ex vivo studies in midbrains and hippocampi revealed that
      neither 5-HT synthesis nor 5-HT and 5-hydroxyindoleacetic acid levels differed
      between strains. [3H]8-Hydroxy-2-(di-n-pro-pylamino)tetralin binding at midbrain
      5-HT1A autoreceptors and hippocampal 5-HT1A postsynaptic receptors,
      [3H]ketanserin binding at cortical and striatal 5-HT2A receptors and
      [3H]citalopram binding at midbrain and hippocampal 5-HT transporters did not vary
      between strains. The inhibition of 5-HT synthesis by 5-HT1A autoreceptor
      stimulation was similar in both strains. Forepaw treading and flat body posture
      after 5-HT1A postsynaptic receptor stimulation were higher and lower,
      respectively, in SHR than in LEW rats. Last, 1-(4-iodo-2,5-dimethoxy-phenyl)-2
      aminopropane- and quipazine-elicited head shakes, a 5-HT2A receptor-mediated
      response, were increased in the SHR strain compared with the LEW strain; on the
      other hand, 1-(3-chlorophenyl)piperazine triggered similar 5-HT2B/2C receptor
      mediated decreases in motor activity in the two strains. This study shows that
      although the low-anxiety (SHR) and high-anxiety (LEW) strains vary in some
      aspects of 5-HT function, key components such as the 5-HT1A autoreceptors are not
      different.

PMID- 9152386
TI  - Catalysis of the cysteine conjugation and protein binding of acetaminophen by
      microsomes from a human lymphoblast line transfected with the cDNAs of various
      forms of human cytochrome P450.
AB  - We have previously found that for acetaminophen kinetic differences exist between
      the hepatic microsomal catalyzed protein binding and cysteine conjugation. We
      have also observed that the protein binding of acetaminophen is only to
      intralumenal proteins. Together these data suggested that two pools of the
      reactive metabolite, N-acetyl-p-benzoquinone imine (NABQI), are formed during the
      oxidative metabolism of acetaminophen: one on the cytosolic surface and the other
      within the lumen of the microsomes. This would indicate that some of forms of
      cytochrome P450 (CYP) catalyzing NABQI formation have their active site on the
      cytosolic surface and others on the lumenal surface. We have examined this
      question by comparing the rates of cysteine conjugation and protein binding of
      acetaminophen by microsomes from lymphoblasts transfected with the cDNAs for
      human CYPs. We found that CYP2D6 catalyzed only cysteine conjugation; CYP1A2 and
      3A4 catalyzed only protein binding; CYP2E1 catalyzed both; and CYP1A1, CYP2A6 and
      CYP2B6 catalyzed neither. These data suggest that CYP2D6 has its active site only
      on the cytosolic surface; CYP1A2 and CYP3A4 only on the lumenal surface; and
      CYP2E1 has catalytic sites on both the lumenal and cytosolic surfaces of the
      membrane. In mouse studies we have found that ethanol administration increased
      acetaminophen protein binding by 265% but cysteine conjugation by only 61%.
      CYP2E1 and CYP2B increased, whereas CYP3A decreased and the others did not
      change. These data suggest that in control mice CYP2E1 catalyzes the bulk of
      protein binding, whereas CYP2D catalyzes slightly more cysteine conjugation than
      does CYP2E1.

PMID- 9152387
TI  - Endothelin receptor antagonists: effect of serum albumin on potency and
      comparison of pharmacological characteristics.
AB  - Endothelins (ETs) are 21-amino acid peptides that bind to membrane receptors to
      initiate pathophysiological effects. Two types of ET receptors, ETA and ETB, have
      been identified. Various ET receptor antagonists are being developed as
      therapeutic agents. This report examines the effects of bovine serum albumin
      (BSA) on the potency of ET receptor antagonists and compares five ET receptor
      antagonists. Competition studies show that in the absence of BSA, A-127722 and L
      749329 inhibited ET-1 binding to ETA receptor with the same IC50 value of 0.09
      nM. Addition of increasing concentrations of BSA incrementally decreased the
      potency of the antagonists: in the presence of 5% BSA, the IC50 values increased
      to 4.3 and 820 nM, respectively. Similarly, addition of BSA decreased the potency
      of antagonists in inhibiting ET-1-stimulated phosphatidylinositol hydrolysis.
      These results suggest that serum albumin has profound effects on the potencies of
      ET receptor antagonists. FR139317, PD-156707, L-749329, Ro-47-0203 and A-127722
      were then selected for direct comparison under identical experimental conditions
      with 0.2% BSA. The potency of antagonists was assessed by binding studies for the
      determination of IC50 and Ki values and by ET-1-stimulated phosphatidylinositol
      hydrolysis and arachidonic acid release for the determination of IC50 and pA2
      values. All five antagonists inhibited ET binding and the biological effects
      exerted by ET in a competitive mode. The Ki values for A-127722, PD-156707,
      FR139317, Ro-47-0203 and L-749329 for the ETA receptor were 0.07, 0.38, 0.80,
      3.67 and 33.6 nM, respectively. A similar hierarchy was revealed by the
      functional assays. Our results suggest that the rank order of potency of the
      antagonists is A-127722 > or = PD-156707 > or = FR139317 > Ro-47-0203 > L-749329.

PMID- 9152388
TI  - Changes in sensitivity to the rate-decreasing effects of opioids in pigeons
      treated acutely or chronically with l-alpha-acetylmethadol.
AB  - The purpose of this study was to examine the effects of acute and chronic
      treatment with l-alpha-acetylmethadol (LAAM), a long-acting mu opioid agonist
      that is used to treat opioid dependence. In pigeons responding under an FR20
      schedule of food presentation, LAAM decreased responding in a dose- and time
      dependent manner, with the largest decrease occurring 4 hr after the
      administration of 5.6 mg/kg. Acute (1.0-5.6 mg/kg) or chronic (1.0-5.6 mg/kg/day)
      treatment with LAAM decreased sensitivity to morphine and increased sensitivity
      to naltrexone, although for both drugs changes in sensitivity were 3- to 10-fold
      greater during chronic treatment. Chronic LAAM treatment (5.6 mg/kg/day) also
      decreased sensitivity to fentanyl and etonitazene by 3-fold and increased
      sensitivity to nalorphine and nalbuphine by 30- and 6-fold, respectively;
      sensitivity to enadoline and ketamine increased only 2- to 3-fold. When LAAM
      treatment was temporarily suspended for 1 day, response rates decreased to 33% of
      control; this disruption was reversed by acute administration of morphine or
      etonitazene. Increased sensitivity to naltrexone and disruptions in responding
      when LAAM treatment was temporarily suspended indicate that dependence developed
      to LAAM. Tolerance and cross-tolerance to agonists as well as increased
      sensitivity to antagonists can be similar during chronic treatment with morphine
      or LAAM; however, increased sensitivity to nalbuphine during LAAM treatment is
      not typically observed during morphine treatment, suggesting that dependence on
      LAAM might not be identical to dependence on morphine. Finally, changes in
      sensitivity to other drugs might predict altered sensitivities to opioids and
      nonopioids in humans receiving LAAM.

PMID- 9152389
TI  - Activation of the alternative pathway of complement by a phosphorothioate
      oligonucleotide: potential mechanism of action.
AB  - Intravenous infusion of high doses of phosphorothioate oligonucleotides in
      monkeys has been associated with transient alterations in hematologic and
      hemodynamic parameters, which appear to be secondary to complement activation.
      ISIS 2302, a phosphorothioate oligonucleotide specific for human intracellular
      adhesion molecule-1, was used to further characterize complement activation in
      monkeys. Complement activation occurred selectively through the alternative
      pathway resulting in increased plasma concentrations of the complement split
      products Bb, C3a and C5a. Marked fluctuations in circulating neutrophil counts
      and reductions in cardiac output were closely associated with peak production of
      anaphylatoxins C3a and C5a. Changing both dose and infusion duration revealed
      that complement activation is related to plasma levels of oligonucleotide, and
      that there is a minimum threshold concentration of approximately 50 micrograms/ml
      of ISIS 2302 that is required to activate complement. Dose regimens in which
      plasma concentrations do not exceed this threshold do not result in complement
      activation. Further investigation reveals that plasma concentrations of a key
      regulatory component of the alternative pathway, Factor H, were also decreased
      after administration of ISIS 2302. Decreases in Factor H levels are suggestive of
      a possible mechanism of complement activation. Direct interaction between ISIS
      2302 and Factor H was demonstrated in a competition assay, where increasing
      concentrations of ISIS 2302 eluted Factor H from a heparin-sepharose column.
      These data demonstrate a clear correlation between plasma oligonucleotide
      concentrations and complement activation. Interactions between ISIS 2302 and
      Factor H may lead to activation of the alternative complement pathway.

PMID- 9152391
TI  - Effects of cadmium and nisoldipine on the delayed rectifier potassium current in
      guinea pig ventricular myocytes.
AB  - Block of the slow inward calcium current (Isi) during assessment of the delayed
      rectifier potassium current (IK) of cardiac ventricular myocytes is commonly
      achieved by use of either inorganic compounds such as cadmium or dihydropyridine
      derivatives such as nisoldipine. Effects of these two Isi blockers on IK
      characteristics of guinea pig ventricular myocytes were compared in this study.
      Currents were measured in the whole cell configuration of the patch-clamp
      technique and IK tail amplitudes were measured at -40 mV after depolarizations to
      various test potentials (voltage steps, -20 to +50 mV) for either 250 (IK250),
      450 (IK450) or 5000 (IK5000) msec. Activating and tail currents measured in the
      presence of cadmium were of greater amplitudes when voltage steps were more
      positive than 0 mV but were of smaller amplitudes at Vtest < or = 0 mV compared
      to currents measured in the presence of nisoldipine or Tyrode solution. In the
      presence of the rapid component of the delayed rectifier E-4031, a blocker of
      cadmium increased IKs amplitude during high voltage tests and caused a positive
      shift in the voltage dependence of IKs activation at low depolarizing potentials.
      In contrast, no effect on IK was observed when nisoldipine was added to Tyrode
      solution. In conclusion, results obtained in this study suggest that cadmium
      depresses and/or shifts the activation curve of the rapid component and increases
      and positively shifts the slow component of IK in guinea pig ventricular
      myocytes. These observations lead us to propose that nisoldipine may be a better
      tool to inhibit long lasting inward calcium current during assessment of IK.

PMID- 9152390
TI  - Structure-activity relationships of a series of [D-Ala2]deltorphin I and II
      analogues; in vitro blood-brain barrier permeability and stability.
AB  - [D-Ala2]deltorphins are enzymatically stable, amphibian heptapeptides that have a
      higher affinity and selectivity for delta-opioid receptors than any endogenous
      mammalian compound known. This study investigated the in vitro blood-brain
      barrier permeability, using primary bovine brain microvessel endothelium culture,
      and the resistance to enzymatic degradation, in mouse 15% brain membrane
      homogenates and 100% plasma, of [D-Ala2]deltorphin I, [D-Ala2]deltorphin II and
      several analogues. Derivatives were designed with the addition of N-terminal
      neutral and basic amino acids or with alterations of the amino acids present
      within the deltorphin sequences. The results indicated that the N-terminal
      sequence and the amino acids in position 4 and 5 are critical to deltorphin
      analogue BBB permeability and biological stability, i.e., t 1/2 brain; 4.8 hr- [D
      Ala2]deltorphin I; > 15 hr- [D-Ala2, Ser4, D-Ala5]deltorphin. Although, no
      analogue was found to increase the BBB permeability coefficient (PC; x10(-4)
      cm/min) of the parent compounds ([D-Ala2]deltorphin II, PC = 23.49 +/- 2.42)
      analogues were identified: [Arg0, D-Ala2]deltorphin II, PC = 19.06 +/- 3.73 and
      [Pro-1, Pro0, D-Ala2]deltorphin II, PC = 22.22 +/- 5.93; which had similar
      permeability coefficients, even though they had larger molecular weights and, in
      the case of the cationic prodrug, a significantly lower lipophilicity. These
      analogues provide directions in the development of future pro-drugs for the
      treatment of pain and this study further clarifies the structure-activity
      relationship of the deltorphins.

PMID- 9152392
TI  - Amantadine inhibits nicotinic acetylcholine receptor function in hippocampal
      neurons.
AB  - The effects of amantadine on nicotinic acetylcholine receptors (nAChRs) of
      hippocampal neurons were studied by recording three types of acetylcholine (ACh)
      evoked currents, using the whole-cell patch-clamp technique. The rapidly
      desensitizing type IA nicotinic current, which is alpha-bungarotoxin-sensitive
      and is mediated by nAChRs bearing alpha 7 subunits, was inhibited by application
      of amantadine to neurons for 10 min (IC50 = 6.5 microM), but the potency of ACh
      (EC50 = 0.27 mM) was not affected by the drug. Amantadine (30-50 microM)
      attenuated the peak current amplitude in a voltage-dependent manner, with greater
      effect at negative than at positive membrane potentials. In contrast, the decay
      phase of the currents was shortened in a voltage-independent manner. When
      amantadine was coapplied briefly with ACh, the drug was markedly less potent
      (IC50 = 130 microM). Thus, the noncompetitive effects of amantadine on the type
      IA nicotinic current are complex, involving actions on the closed and
      desensitized states of the alpha 7 nAChR. The slowly desensitizing, alpha
      bungarotoxin-insensitive nicotinic currents of type II, which is inhibited by
      dihydro-beta-erythroidine and is mediated by alpha 4 beta 2 nAChRs, and of type
      III, which is inhibited by mecamylamine and is mediated by alpha 3 beta 4 nAChRs,
      were also sensitive to inhibition by amantadine. The peak amplitude of type II
      current was reduced only slightly by 10 microM amantadine coapplied with ACh, but
      the decay-time constant and amplitude of the sustained current were markedly
      reduced. Type III current was also inhibited when amantadine was briefly
      coapplied with ACh. In contrast to its effects on nicotinic currents, amantadine
      at 10 microM did not affect currents evoked by N-methyl-D-aspartate plus glycine,
      gamma-aminobutyric acid, glycine or kainate. Thus, on cultured hippocampal
      neurons, amantadine preferentially inhibits nicotinic currents.

PMID- 9152393
TI  - FP prostaglandin receptors mediating inositol phosphates generation and calcium
      mobilization in Swiss 3T3 cells: a pharmacological study.
AB  - A detailed pharmacological characterization of the prostaglandin (PG) receptor
      coupled to phosphoinositide (PI) turnover and intracellular calcium mobilization
      in Swiss 3T3 mouse fibroblast cells was undertaken. The pharmacological profile
      of this functional receptor was compared with the pharmacological profile of
      specific [3H]PGF2 alpha binding to bovine corpus luteum membranes, which are
      known to contain a bona fide FP receptor. PGs that were potent stimulators and
      full agonists in the PI turnover assay in the 3T3 cells were the following (for
      all, n = 3-45): 16-phenoxy-PGF2 alpha (EC50 = 0.61 +/- 0.1 nM), cloprostenol
      (EC50 = 0.73 +/- 0.04 nM), 17-phenyl-PGF2 alpha (EC50 = 2.71 +/- 0.35 nM),
      fluprostenol (EC50 = 3.67 +/- 0.61 nM), PhXA85 (EC50 = 27.3 +/- 5.63 nM) and PGF2
      alpha (EC50 = 28.5 +/- 5.26 nM). However, PGD2 (EC50 = 155 +/- 29.9 nM; Emax =
      49% of cloprostenol), PGE2 (EC50 = 2570 +/- 566 nM; Emax = 59%) and U46619 (EC50
      = 1060 +/- 310 nM; Emax = 63%) were less potent and were partial agonists, and
      iloprost and BW245C were inactive. Although the PGs tested exhibited lower
      affinities in the 3[H]PGF2 alpha binding assay than their functional potencies in
      the PI turnover assay, the rank orders of potencies and affinities were well
      correlated (r = 0.94; n = 15 compounds). However, the PI turnover assay was more
      sensitive than the calcium mobilization assay for rank ordering PG agonists. In
      conclusion, the Swiss 3T3 cells express an FP receptor coupled to PI turnover and
      intracellular Ca+2 mobilization signal transduction pathways. The pharmacological
      profile of this receptor was similar to that of the FP receptor found in the
      bovine corpus luteum, a tissue previously used to clone the first
      pharmacologically defined FP receptor.

PMID- 9152394
TI  - The pyrethroids permethrin and cyhalothrin are potent inhibitors of the
      mitochondrial complex I.
AB  - The synthetic pyrethroid derivatives permethrin and cyhalothrin are widely used
      insecticides that are considered to be relatively nontoxic to higher animals.
      However, a variety of toxic effects on mammals have been reported. We
      investigated the effect of these drugs on energy coupling by mitochondria and on
      the activity of the individual respiratory complexes. Using isolated rat liver
      mitochondria, a concentration-dependent inhibition of glutamate and succinate
      sustained state 3 respiration was found for both compounds in the micromolar
      range. The effect of pyrethroids on the activities of the complexes I to V were
      assessed individually in submitochondrial particles (complex I) and in freeze
      thawed mitochondria (complexes II-V). Complex I (EC 1.6.5.3) was found to be the
      most sensitive link within the electron transport chain. Half-maximal inhibition
      was observed at 0.73 microM permethrin and 0.57 microM cyhalothrin, respectively,
      and exhibited sigmoidal inhibition kinetics. Complexes II, III, IV and V (EC
      1.3.5.1, 1.10.2.2, 1.9.3.1, 3.6.1.34) were not significantly inhibited by up to
      50 microM of these drugs. Thus, our results reveal a model of action of synthetic
      pyrethroid insecticides not previously reported.

PMID- 9152395
TI  - Thrombin receptor-activating peptide releases arachidonic acid from human
      platelets: a comparison with thrombin and trypsin.
AB  - The serine proteases thrombin and trypsin are both powerful platelet agonists
      that act by cleaving the terminal portion of the thrombin receptor and allowing
      the new C-terminal to auto-stimulate the receptor. Synthetic peptides, termed
      thrombin receptor-activating peptides (TRAPs), have been shown to mimic many of
      the effects of thrombin. Here we have compared the effects of inhibitors on
      platelet aggregation and [14C]-arachidonic acid release in response to thrombin,
      trypsin and TRAP. Pretreatment of human platelets with BW755C (80 microM), which
      inhibits both cyclooxygenase and lipoxygenase, blocked trypsin (15-20 nM)- or
      TRAP (4-6 microM)-induced aggregation, but not thrombin (0.06-0.1 U/ml)-induced
      aggregation. The protease inhibitor leupeptin (10 micrograms/ml) abolished
      trypsin-induced aggregation and returned [14C]-arachidonic acid release from
      [14C]-arachidonic acid-prelabeled platelets to control levels. In contrast,
      leupeptin did not affect either aggregation or [14C]-arachidonic acid release in
      platelets stimulated by TRAP. Thrombin-induced aggregation and [14C]-arachidonic
      acid release were only partially inhibited by leupeptin. These data are
      consistent with the activation of platelets by both trypsin and TRAP occurring
      via the proteolytic receptor, whereas thrombin-induced platelet activation
      appears to occur by a dual mechanism of action. One component of thrombin-induced
      platelet activation is by a proteolytic action on the moderate-affinity receptor.
      This effect is sensitive to inhibition by leupeptin and is mimicked by trypsin
      and TRAP. The other component of thrombin is nonproteolytic and may occur by an
      action at a high-affinity receptor such as glycoprotein lb.

PMID- 9152396
TI  - M1 receptor agonist activity is not a requirement for muscarinic antinociception.
AB  - The analgesic effects of a series of muscarinic agonists were investigated by use
      of the mouse acetic acid writhing, grid-shock, hot-plate and tail-flick tests.
      The compounds tested were oxotremorine, pilocarpine, arecoline, aceclidine, RS86
      and four 3-3(substituted-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahy-dro-1 -methyl
      pyridines (substituted TZTP), these being propoxy-TZTP, 3-Cl-propylthio-TZTP,
      xanomeline (hexyloxy-TZTP) and hexylthio-TZTP. These agonists were also assayed
      for their ability to displace [3H]oxotremorine-M and [3H]pirenz-epine binding and
      for their functional selectivity at pharmaco-logic M1, M2 and M3 receptors. These
      compounds all produced dose-dependent antinociceptive effects in all of the mouse
      analgesia tests. The effects of oxotremorine in the writhing test were fully
      antagonized by the muscarinic antagonist scopolamine (0.1 mg/kg), but only
      partially antagonized by methsco-polamine (10 mg/kg) and unaffected by the opioid
      antagonist naltrexone. 3-Cl-propylthio-TZTP and propoxy-TZTP had virtually no
      effect at the M1 receptor subtype as measured by the human m1 clone expressed in
      baby hamster kidney cells or the rabbit vas deferens assay. These compounds,
      however, were more potent in the analgesia tests than the selective M1 agonists
      xanomeline and hexylthio-TZTP. These data suggest that muscarinic analgesia is
      mediated by central muscarinic receptors. However, activity at the M1 receptor
      subtype is not a requirement for antinociceptive activity.

PMID- 9152397
TI  - Butylthio[2.2.2] (NNC 11-1053/LY297802): an orally active muscarinic agonist
      analgesic.
AB  - Butylthio[2.2.2] ((+)-(S)-3-(4-(Butylthio)-1,2,5-thiadiazol-3-yl)-1
      azabicyclo[2.2. 2] octane) is an agonist/antagonist at muscarinic receptors. The
      analgesic potential of butylthio[2.2.2] was assessed in the mouse by use of the
      grid-shock, tail-flick, hotplate and writhing tests. The ED50 values ranged from
      0.19 to 1.47 mg/kg and 1.51 to 12.23 mg/kg 30 min after s.c. and p.o.
      administration, respectively, yielding p.o./s.c. ratios ranging from 7 to 27. The
      ED50 values for salivation and tremor were > 30 and 12.31 mg/kg s.c., and > 60
      and > 60 mg/kg p.o., yielding therapeutic windows > 130 and 54, and, > 40 and >
      40, after s.c. and p.o. administration, respectively. Motor impairment or
      lethality were only seen at doses 116 and 254 times higher than the
      antinociceptive doses. Butylthio[2.2.2] was equieffective to, and 3- to 24-fold
      more potent than morphine. The duration of action was similar to that of
      morphine. The dose-response curve was shifted dose dependently to the right by
      the muscarinic antagonist scopolamine but not by the opioid antagonist
      naltrexone. The antinociceptive effect of butylthio[2.2.2] was reversed by the
      centrally acting muscarinic antagonist scopolamine but not by the peripherally
      acting muscarinic antagonist methscopolamine. After 6.5 days repeated dosing in
      mice, morphine produced marked tolerance, whereas butylthio[2.2.2] produced
      minimal, if any, tolerance. In the rat grid-shock test, ED50 values of 0.26 mg/kg
      s.c. and 25.28 mg/kg p.o. were obtained. These data show that butylthio[2.2.2] is
      a potent and efficacious antinociceptive with a very favorable therapeutic window
      after s.c. and p.o. administration in mice, and with good efficacy in rats.

PMID- 9152398
TI  - Pharmacology of butylthio[2.2.2] (LY297802/NNC11-1053): a novel analgesic with
      mixed muscarinic receptor agonist and antagonist activity.
AB  - Butylthio[2.2.2], ((+)-(S)-3-(4-butylthio-1,2,5-thiadiazol-3-yl)-1
      azabicyclo[2.2.2] octane; LY297802/NNC11-1053) is a muscarinic receptor ligand
      which is equiefficacious to morphine in producing antinociception. In vitro,
      butylthio[2.2.2] had high affinity for muscarinic receptors in brain homogenates,
      but had substantially less or no affinity for several other neurotransmiter
      receptors and uptake sites. In isolated tissues, butylthio[2.2.2] was an agonist
      with high affinity for M1 receptors in the rabbit vas deferens (IC50 = 0.33 nM),
      but it was an antagonist at M2 receptors in guinea pig atria (pA2 = 6.9) and at
      M3 receptors in guinea pig urinary bladder (pA2 = 7.4) and a weak partial agonist
      in guinea pig ileum, which contains a heterogeneous population of muscarinic
      receptors. In vivo, butylthio[2.2.2] was without effect on acetylcholine,
      dopamine and serotonin levels in rat brain. Moreover, butylthio[2.2.2] did not
      decrease charcoal meal transit in mice, nor did it significantly alter heart rate
      in rats. Further, butylthio[2.2.2] did not produce parasympathomimetic effects
      such as salivation or tremor in mice, but it antagonized salivation and tremor
      produced by the nonselective muscarinic agonist oxotremorine. The present data
      demonstrate that butylthio[2.2.2] is a novel muscarinic receptor mixed
      agonist/antagonist and its pharmacological profile suggests that it may have
      clinical utility in the management of pain as an alternative to opioids.

PMID- 9152399
TI  - Pyrrolopyrimidines: novel brain-penetrating antioxidants with neuroprotective
      activity in brain injury and ischemia models.
AB  - A novel group of antioxidant compounds, the pyrrolopyrimidines, has been
      discovered recently. Many of these possess significantly improved oral
      bioavailability (56-70% in rats), increased efficacy and potency in protecting
      cultured neurons against iron-induced lipid peroxidative injury and as much as a
      5-fold increase in brain uptake compared with the 21-aminosteroid antioxidant
      compound, tirilazad mesylate (U-74006F), described earlier. They appear to quench
      lipid peroxidation reactions by electron-donating and/or radical-trapping
      mechanisms. Several compounds in the series, such as U-101033E and U-104067F,
      demonstrate greater ability than tirilazad to protect the hippocampal CA1 region
      in the gerbil transient (5-min) forebrain ischemia model. Delaying treatment
      until 4 hr after the ischemic insult still results in significant CA1 neuronal
      protection. U-101033E is still effective in salvaging a portion of the CA1
      neuronal population when the ischemic duration is extended to 10 min. In
      addition, U-101033E has been found to be protective in the context of focal
      cerebral ischemia, reducing infarct size in the mouse permanent middle cerebral
      artery occlusion model, in contrast to tirilazad which is minimally effective.
      These results suggest that antioxidant compounds with improved brain parenchymal
      penetration are better able to limit certain types of ischemic brain damage than
      those which are localized in the cerebral microvasculature. However, the activity
      of U-101033E in improving early post-traumatic recovery in mice subjected to
      severe concussive head injury is similar to that of tirilazad. Last, the oral
      bioavailability of many pyrrolopyrimidines suggests that they may be useful for
      certain chronic neurodegenerative disorders in which lipid peroxidation plays a
      role.

PMID- 9152400
TI  - Evidence for spare nicotinic acetylcholine receptors and a beta 4 subunit in
      bovine adrenal chromaffin cells: studies using bromoacetylcholine, epibatidine,
      cytisine and mAb35.
AB  - Relatively little is known about the type and number of nicotinic acetylcholine
      receptors (nAChRs) that mediate secretion from adrenal chromaffin cells. In these
      studies, we investigated nAChR reserve pools and their modulation using
      bromoacetylcholine (brACh) and the anti-nAChR antibody mAb35. By using brACh
      under acetylating conditions, adrenal catecholamine release was reduced (IC50,
      approximately 0.3 microM). This effect was slowly reversible. Submaximal
      concentrations of brACh caused shifts to the right in concentration-response
      curves of approximately 4-fold, as well as decreases in Emax values for the
      agonists nicotine and epibatidine. Cytisine is a nAChR agonist (EC50,
      approximately 46 microM) that was somewhat less efficacious than nicotine (Emax,
      approximately 85% of 10 microM nicotine) in adrenal chromaffin cells. Submaximal
      concentrations of brACh caused a small shift to the right in the concentration
      response curves for the agonist cytisine, as well as a decrease in the Emax
      value. mAb35, which causes a slowly developing loss of nAChR-mediated secretion,
      produced a time-dependent shift to the right in agonist concentration-response
      curves and a reduction in Emax for nicotine and epibatidine. mAb35 treatment
      produced only a reduction in the Emax value of cytisine. Finally, we cloned and
      sequenced a reverse transcription-polymerase chain reaction product from bovine
      adrenal chromaffin RNA that shares a high degree of homology with beta 4 nAChR
      subunits. Northern analysis provided evidence for the presence of this transcript
      in chromaffin cell cultures. Together, these studies support the presence of a
      nAChR reserve in adrenal chromaffin cells that is down-regulated by mAb35. These
      studies also support the presence of more than one nAChR population mediating
      secretion and the presence of beta 4 nAChR subunits.

PMID- 9152401
TI  - Interindividual variability in expression and activity of human beta
      glucuronidase in liver and kidney: consequences for drug metabolism.
AB  - Glucuronidation of drugs represents a major pathway of human drug metabolism.
      Numerous studies show that the glucuronides formed can accumulate during chronic
      therapy and/or have direct pharmacological activity. In both cases, cleavage of
      the glucuronide by human beta-glucuronidase (beta-Gluc) would release the parent
      compound, thereby modifying drug disposition. Variability in expression of beta
      Gluc could therefore be a confounding factor for interindividual variability in
      drug disposition both in the setting of accumulating glucuronides or for the use
      of glucuronides as prodrugs, such as the nontoxic glucuronide-spacer derivative
      of doxorubicin (Dox-S-G). We therefore investigated expression and function of
      beta-Gluc in human liver (n = 30) and human kidney (n = 18). Cleavage of the
      model compound 4-methylumbelliferyl-beta-D-glucuronide (MUG) revealed a wide
      range of activities in liver (0.32-1.85 mumol/mg/h, mean value 0.87 +/- 0.34
      mumol/mg/h) and kidney (0.07-1.00 mumol/mg/h, mean 0.39 +/- 0.21 mumol/mg/h),
      which followed a log normal distribution. Variable enzyme activity was closely
      correlated to enzyme expression as assessed by Western blotting (r = 0.80, P <
      .001 and r = 0.71, P < .05 for liver and kidney, respectively). Glycyrrhizin (Ki
      = 470 and 570 microM), estradiol 3-glucuronide (Ki = 0.9 and 1.2 mM) and
      paracetamol glucuronide (Ki = 1.6 and 2 mM) were found to inhibit beta-Gluc
      activity competitively in liver and kidney, respectively. Enzyme kinetics were
      investigated in detail for MUG and Dox-S-G. Whereas MUG followed monophasic
      Michaelis-Menten kinetics in liver (K(m) = 1.32 +/- 0.25 mM, Vmax = 1201 +/- 462
      nmol/mg/h, n = 3) and kidney (K(m) = 1.04 +/- 0.05 mM, Vmax = 521 +/- 267
      nmol/mg/h, n = 3), cleavage of Dox-S-G was best described by the Hill equation,
      which indicated a cooperative substrate binding pattern of Dox-S-G. In summary,
      beta-Gluc function shows wide interindividual variability in human liver and
      kidney that is due to different steady-state levels of the enzyme. Moreover,
      enzyme kinetics are substrate-dependent, with Dox-S-G showing a cooperative
      binding. These data indicate the possibility of wide interindividual variability
      in beta-Gluc-mediated cleavage of drug glucuronides in the human.

PMID- 9152402
TI  - Effects of a novel free radical scavenger, MCl-186, on ischemic brain damage in
      the rat distal middle cerebral artery occlusion model.
AB  - We investigated the effects of a free radical scavenger, 3-methyl-1-phenyl-2
      pyrazolin-5-one (MCl-186), on infarct areas, neurological deficits and regional
      cerebral blood flow (rCBF), with use of a rat thrombotic distal middle cerebral
      artery (dMCA) occlusion model to elucidate its possible therapeutic effects on
      focal cerebral ischemia. In addition, we have attempted to measure 2-oxo-3
      (phenylhydrazono)-butanoic acid (OPB), which is the major oxidation product of
      MCl-186, in the penumbral cortex of a thrombotic dMCA occlusion model.
      Postischemic treatment with MCl-186 (3 mg/kg) significantly (P < .05) decreased
      the size of the cerebral infarcts 1 day after dMCA occlusion. MCl-186 (3 mg/kg)
      significantly (P < .05) improved the neurological deficits 1 day after dMCA
      occlusion. On the contrary, MCl-186 had no effect on rCBF 1 day after dMCA
      occlusion. MCl-186 mainly reacted into OPB by peroxidation in rat brain
      homogenates. Furthermore, the increase in OPB content in the ischemic penumbral
      cortex tissue was confirmed after 90 min of MCl-186 perfusion. These results
      suggest that MCI-186 has a protective effect on brain ischemia by reacting with
      oxygen radicals and that oxygen radicals are closely related to postischemic
      brain injury.

PMID- 9152403
TI  - N-methyl-D-aspartate receptors in associative eyeblink conditioning: both MK-801
      and phencyclidine produce task- and dose-dependent impairments.
AB  - The effects of N-methyl-D-aspartate receptor blockade on two major variants of
      rabbit eyeblink conditioning were evaluated using a selective noncompetitive
      antagonist, [5R, 10S]-[+]-5-methyl-10, 11-dihydro-5H-dibenzo[a, d] cyclo-hepten
      5,10-imine hydrogen maleate; dizocilpine (MK-801) or phencyclidine (PCP), a drug
      of abuse. Either MK-801 or PCP (given daily) impaired rabbits' ability to
      associate tone conditioned stimuli with airpuff unconditioned stimuli, with the
      severity of impairment exhibiting clear dose and task dependencies. Trace
      conditioned rabbits given > or = 80 micrograms/kg of MK-801 or > or = 1.0 mg/kg
      of PCP failed to reach a criterion of 80% conditioned responses during training,
      with significant impairments seen at intermediate doses. Delay-conditioned
      rabbits, although dose-dependently slowed, successfully acquired the task, even
      when given doses of MK-801 or PCP that completely blocked acquisition in trace
      conditioning. Additionally, even low doses of MK-801 (10 micrograms/kg) or of PCP
      (0.1 mg/kg) severely altered conditioned response timing in trace but not in
      delay conditioning, resembling effects observed after hippocampal lesions. Doses
      of MK-801 or PCP that impaired acquisition also severely impaired extinction of
      both trace- and delay-conditioned eyeblink responses. However, neither MK-801 nor
      PCP altered retention or timing of previously learned responses. Higher doses of
      MK-801 (> or = 200 micrograms/kg) or of PCP (> or = 2.0 mg/kg) dose-dependently
      impaired unconditioned response performance, although lower doses of MK-801 (< or
      = 160 micrograms/kg) or of PCP (< or = 1.0 mg/kg) had no effects on unconditioned
      responses or on non-associative pseudoconditioned responses. The deficits
      observed indicate that although not necessary for retention, N-methyl-D-aspartate
      receptor activation may facilitate acquisition of delay-conditioning. N-methyl-D
      aspartate receptor activation appears to be necessary for acquisition of trace
      conditioning, and for extinction in either paradigm.

PMID- 9152404
TI  - An antisense oligonucleotide on the mouse Shaker-like potassium channel Kv1.1
      gene prevents antinociception induced by morphine and baclofen.
AB  - Inactivation of the Kv1.1 gene, which codes for a member of the Shaker-like
      potassium channels by an antisense oligodeoxyribonucleotide (aODN), was carried
      out in mice. The effect of this inactivation on analgesia induced by morphine (5
      9 mg kg-1 s.c.) and baclofen (2-5 mg kg-1 s.c.) was investigated in the mouse hot
      plate test. Mice received a single intracerebroventricular injection of mKv1.1
      aODN (0.5, 1.0, 2.0 or 3.0 nmol per injection), degenerated ODN or vehicle on
      days 1, 4 and 7. A dose-dependent inhibiton of morphine and baclofen
      antinociception was observed 72 h after the last intracerebroventricular aODN
      injection, whereas degenerated ODN and vehicle, used as controls, did not affect
      morphine- and baclofen-induced antinociception. Sensitivity to both analgesic
      drugs returned to the normal range 7 days after the end of the aODN treatment,
      which indicated the absence of any irreversible damage or toxicity caused by
      aODN. Quantitative reverse transcription-polymerase chain reaction analysis
      demonstrated that a decrease in mKv1.1 mRNA levels occurred only in the aODN
      treated group, being absent in all control groups. Furthermore, neither aODN,
      degenerated ODN nor vehicle produced any behavioral impairment of mice. These
      results indicate that the mKv1.1 potassium channel, whose gene expression we
      specifically modulated by means of the antisense ODN strategy, plays an important
      role in central analgesia induced by morphine and baclofen.

PMID- 9152405
TI  - Effects of the 5-lipoxygenase inhibitor A-64077 on intestinal hypothermic organ
      preservation injury.
AB  - The effects of the orally active selective 5-lipoxygenase inhibitor Zileuton (A
      64077, (N-1(1-benzo{b}thien-2-ylethyl)-N-hydroxyurea) were studied in a canine
      model of hypothermic intestinal organ ischemia-reperfusion (I/R) injury
      (transplant preservation injury). Forty-eighty hours of hypothermic intestinal
      ischemia utilizing Collin's flush, followed by 1 hr of reperfusion
      (transplantation) in A-64077-treated animals, resulted in a 3-fold increase in
      intestinal oxygen uptake and blood flow relative to the untreated controls. The
      postreperfusion movement of fluid from the microcirculation into the intestinal
      lumen significantly increased in the control animals at reperfusion, and A-64077
      treatment dramatically exacerbated this phenomenon. Mucosal neutrophil
      infiltration, or the processes leading to infiltration, significantly increased
      after 48 hr of cold ischemia and 1 hr of normothermic reperfusion in the
      untreated animals. A similar response was observed in A-64077-treated dogs, but
      the absolute levels of MPO were 10-fold less relative to untreated animals,
      including intestinal tissue obtained before I/R. Hypothermic I/R injury in this
      model resulted in severe histologic injury. A-64077-treated dogs, however,
      demonstrated significant improvements in histologic injury. Mucosal synthesis of
      LTB4 rose significantly after cold I/R injury and was abrogated by A-64077
      treatment. The synthesis of PGE2 significantly increased after cold I/R in both
      untreated and A-64077-treated dogs. The increase in PGE2 production after
      hypothermic I/R in the A-64077-treated animals was higher relative to the
      untreated control animals. In conclusion, this study indicates that arachidonic
      acid metabolism via the 5-lipoxygenase pathway plays a significant role in the
      pathophysiology of hypothermic intestinal I/R injury. Furthermore, the 5
      lipoxygenase inhibitor A-64077 possesses favorable pharmacologic and biologic
      responses in this intestinal injury and should be considered in the clinical
      amelioration of intestinal transplantation preservation injury.

PMID- 9152406
TI  - The human thromboxane A2 receptor alpha isoform (TP alpha) functionally couples
      to the G proteins Gq and G11 in vivo and is activated by the isoprostane 8-epi
      prostaglandin F2 alpha.
AB  - To establish whether the thromboxane A2 (TXA2) receptor (TP) functionally couples
      to the Gq family of heterotrimeric G proteins in vivo, we have coexpressed the
      cDNAs coding for the human platelet/placental TP alpha isoform (TP alpha) and the
      alpha subunits of Gq or G11 in human embryonic kidney (HEK) 293 cells. TP
      activation in response to ligand stimulation was monitored by analyzing
      mobilization of intracellular calcium (Ca++i) in FURA2/AM-loaded transfected HEK
      293 and in platelets. Second, we wished to examine the possible interaction of
      the isoprostane 8-epi prostaglandin F2 alpha with the TP alpha, in transfected
      HEK 293 cells and with the TPs expressed in platelets. Thus both the
      prostaglandin endoperoxide/TXA2 analog (U46619) and the 8-epi PGF2 alpha were
      utilized as ligand probes of TP alpha activation. The results demonstrate that
      each ligand induced elevations of Ca++i levels in HEK 293 cells, cotransfected
      with either the TP alpha and G alpha q or the TP alpha and G alpha 11, and also
      in platelets. Initial stimulation of these cells with U46619 or 8-epi PGF 2 alpha
      desensitized a subsequent rise in [Ca++]i in response to U46619 or 8-epi PGF 2
      alpha, respectively. Moreover, prestimulation with U46619 desensitized a
      subsequent rise in Ca++i concentration in response to 8-epi PGF 2 alpha, and vice
      versa. These responses were blocked by the TP antagonist SQ29,548 in both cell
      types. In contrast, prestimulation of the transfected HEK 293 cells or platelets
      with thrombin did not desensitize a subsequent rise in [Ca++]i in response to
      U46619 or 8-epi PGF 2 alpha. After stimulation with either U46619 or 8-epi PGF 2
      alpha, no significant rise in Ca++i levels was observed in HEK 293 cells
      transfected with the TP alpha receptor only or in control cells transfected with
      the vector pCMV5. These results demonstrate that the TP alpha isoform
      functionally couples with either Gq or G11 in vivo, whether activated by a
      PG/TXA2 analog or by the F2 isoprostane 8-epi PGF2 alpha.

PMID- 9152407
TI  - Age-related deficits in the cerebellar beta adrenergic signal transduction
      cascade in Fischer 344 rats.
AB  - Localization of age-related deficits in the cerebellar beta adrenergic signal
      transduction cascade were investigated electrophysiologically using forskolin
      (FORSK) and adenosine-3',5'-cyclic monophosphothioate Sp-isomer (Sp-cAMPS)
      applied via pressure ejection from extracellular multibarreled glass electrodes
      to activate the transduction cascade. In young rats, 100 microM FORSK activated
      AC, and 100 microM Sp-cAMPS activated protein kinase A; thus, both increased
      GABAergic inhibition of Purkinje cell firing. In aged rats, however, 100 microM
      FORSK was unable to increase GABAergic inhibition of Purkinje cell firing. In
      addition, 1 mM 7 beta-decacetyl-7 beta-(gamma-N-methylpiperazino)butyryl
      forskolin, an analog of FORSK, was also unable to increase GABAergic inhibition
      in aged rats. In contrast, Sp-cAMPS was able to increase GABAergic inhibition in
      aged rats, but higher doses were required than in young rats, Isoproterenol
      (ISO), a beta adrenergic agonist, was ineffective in increasing GABAergic
      inhibition of Purkinje firing in aged rats when tested alone, but ISO was
      effective in increasing Purkinje cell inhibition when ISO was tested with Sp
      cAMPS. The results of this experiment indicate that one age-related deficit in
      the cerebellar beta adrenergic system occurs at the level of protein kinase A
      activation.

PMID- 9152408
TI  - The full D1 dopamine receptor agonist SKF-82958 induces neuropeptide mRNA in the
      normosensitive striatum of rats: regulation of D1/D2 interactions by muscarinic
      receptors.
AB  - Neuropeptide and immediate early gene expression in striatonigral neurons of the
      normosensitive striatum is induced by mixed D1/D2 receptor agonists and indirect
      dopamine agonists, such as cocaine and amphetamine. Both D1 and D2 receptor
      antagonists block these events. In contrast, the partial D1 agonist, SKF-38393,
      does not evoke striatonigral gene expression in intact rats. These findings have
      contributed to the idea that both D1 and D2 receptors must be stimulated to evoke
      gene expression in striatonigral neurons. How these "D1/D2 interactions" are
      accomplished is unclear in light of the controversy over whether striatonigral
      neurons express both D1 and D2 receptors. This study addresses these issues by
      demonstrating that in intact rats 1) a full D1 receptor agonist, SKF-82958,
      induced behavioral activity and preprodynorphin (PPD) and substance P (SP) gene
      expression in medium spiny neurons in the dorsal, and especially, in the ventral
      striatum, 2) either a D1 antagonist, SCH-23390, or a D2 antagonist, eticlopride,
      blocked these effects, 3) the muscarinic antagonist, scopolamine, augmented PPD
      and SP mRNA expression induced by SKF-82958 and prevented the ability of
      eticlopride to block SKF-82958-induced PPD and SP mRNAs and 4) the SKF-82958
      induced increase in preproenkephalin mRNA in striatopallidal neurons was blocked
      by SCH-23390 or scopolamine but not by eticlopride. These data indicate that
      endogenous acetylcholine attenuates D1 receptor-stimulated PPD/SP gene expression
      in medium spiny neurons, mediates D1 receptor-stimulated preproenkephalin gene
      expression in striatopallidal neurons and contributes to D2 receptor involvement
      in D1-stimulated PPD/SP gene expression.

PMID- 9152409
TI  - HepG2 and SK-N-MC: two human models to study alpha-2 adrenergic receptors of the
      alpha-2C subtype.
AB  - It is now clearly established that alpha-2 adrenergic receptors can be subdivided
      in three pharmacological subtypes (alpha-2A, alpha-2B and alpha-2C) encoded by
      distinct genes (alpha 2C10, alpha 2C2 and alpha 2C4, respectively, in humans).
      Whereas the study of the regulation of the human alpha-2A adrenergic receptor and
      of the promoter region of the alpha 2C10 gene has being greatly helped by the
      availability of the colon carcinoma cell line HT29, the study of the other human
      receptor subtypes has thus far been limited to homologous desensitization/down
      regulation in transfected cells, because of the lack of human cellular models
      constitutively-expressing alpha-2B or alpha-2C adrenergic receptors. Several
      human cell lines were thus screened, in an attempt to find such models.
      Radioligand binding studies with [3H]RX821002 and [3H]MK912, reverse
      transcription-polymerase chain reactions and RNase mapping experiments with pairs
      of primers and riboprobes specific for each subtype demonstrated that the
      hepatoma cell line HepG2 and the neuroblastoma cell line SK-N-MC possess alpha-2
      adrenergic receptors of the alpha-2C subtype. However, whereas HepG2 expresses
      exclusively alpha-2C receptors (55 +/- 7 fmol of [3H]MK912 binding sites/mg of
      protein), SK-N-MC expresses both alpha-2A and alpha-2C subtypes in fairly similar
      amounts (20 +/- 8 and 23 +/- 3 fmol of [3H]MK912 binding sites/mg of protein,
      respectively). The study of the inhibition of 3H-labeled antagonist binding by
      UK14304 demonstrated that a fraction of the receptor population was coupled to
      pertussis toxin-sensitive G-proteins, which were identified as Gi2 and Gi3 by
      immunoblotting. The alpha-2 agonist was, moreover, able to decrease forskolin
      stimulated cAMP production by 47% in HepG2 and 23% in SK-N-MC, demonstrating that
      inhibition of adenylyl cyclase is one of the primary mechanisms of signal
      transduction in both cell lines. HepG2 and SK-N-MC are the first human cell lines
      unquestionably shown to natively express alpha-2C adrenergic receptors. The
      discovery of these two models may be useful for future study of the regulation of
      alpha 2C4 gene expression in cells of different origins and investigation of the
      reciprocal regulation of alpha-2A and alpha-2C subtype in single cells.

PMID- 9152410
TI  - Expression of hygR in transgenic mice causes resistance to toxic effects of
      hygromycin B in vivo.
AB  - Aminoglycoside antibiotics are indispensable for treatment of serious bacterial
      infections, and despite careful attention to dosage regimens, nephrotoxicity and
      ototoxicity still cause concern. In the present study, we tested whether side
      effects of aminoglycoside therapy could be limited by expression of prokaryotic
      genes of antibiotic resistance in vivo. We characterized the acute and tissue
      specific toxicity of hygromycin B in transgenic mice bearing the hygromycin B
      phosphotransferase (hygR) gene under control of a constitutive promoter. We
      characterized the tissue-specific expression of hygR mRNA and also investigated
      the acute toxicity of hygromycin B in hygR and wild-type mice. The hygR mRNA
      reached its highest levels in brain and reached intermediate levels in spleen,
      muscle, kidney, liver and testis. The lowest levels were detected in heart and
      lungs. The hygR expression in transgenic animals caused an 89-fold increase in
      the approximate lethal dose of hygromycin B compared with wild-type mice. Serum
      biochemical analysis of hygR and wild-type mice treated with lethal doses of
      hygromycin B indicated liver and kidney damage measured as ALT, AST and BUN. On
      the morphological level, these changes led to acute tubular nephrosis in wild
      type mice and acute liver damage in hygR mice. Our results show that constitutive
      expression of the bacterial hygR gene in transgenic mice in vivo confers
      resistance to hygromycin B.

PMID- 9152411
TI  - Activation of mu opioid receptors inhibits microglial cell chemotaxis.
AB  - Opiates modulate many macrophage functions. Microglia, the resident macrophages
      of the brain, migrate to sites of inflammation within the CNS. Using primer sets
      designed to span the entire open reading frame of the human brain mu opioid
      receptor (MOR), we found that microglial cells constitutively expressed MOR mRNA.
      The cDNA sequences of the MOR open reading frame in microglia were identical to
      those of human brain tissue. Using enriched human fetal microglial cell cultures,
      we found that morphine potently inhibited the directed migration (chemotaxis) of
      microglial cells toward C5a in a dose-dependent manner with an IC50 value of 1 fM
      morphine. We also found that DAMGO, a selective MOR ligand, dose-dependently
      suppressed microglial cell chemotaxis with an IC50 value of 1 nM, which was
      significantly attenuated by 10 nM beta-funaltrexamine. Taken together, these
      findings suggest that activation of constitutively expressed MOR inhibits
      microglial cell chemotaxis and support the notion of an anti-inflammatory role of
      MOR within the brain.

PMID- 9152412
TI  - Prostaglandin E2 production dependent upon cyclooxygenase-1 and cyclooxygenase-2
      and its contradictory modulation by auranofin in rat peritoneal macrophages.
AB  - Rat peritoneal macrophages were incubated in the presence of cycloheximide or
      dexamethasone to inhibit the induction of cyclooxygenase (COX)-2 protein
      synthesis. Thereafter, when the macrophages were incubated in the presence of
      arachidonic acid, PGE2 production was increased. Western blot analysis
      demonstrated that COX-2 protein levels were low and were not affected by
      arachidonic acid treatment. COX-1 protein levels were not affected by arachidonic
      acid treatment either. The COX-2 inhibitors NS-398 and nimesulide only slightly
      inhibited PGE2 production, whereas the COX-1/COX-2 inhibitors indomethacin,
      piroxicam and tenoxicam strongly inhibited PGE2 production. This suggests that
      under these conditions, PGE2 production is dependent on COX-1. After the
      macrophages were treated with aspirin to inactivate existing COX-1 and COX-2,
      however, treatment with 12-0-tetradecanoylphorbol 13-acetate increased PGE2
      production. Furthermore, COX-2 protein levels were markedly increased by 12-0
      tetradecanoylphorbol 13-acetate treatment, whereas COX-1 protein levels did not
      change. In this case, both the COX-2 and the COX-1/ COX-2 inhibitors inhibited
      PGE2 production. This suggest that under these conditions, PGE2 production is
      dependent on COX-2. Effects of auranofin on COX-1-dependent and COX-2-dependent
      PGE2 production were examined. We found that auranofin stimulated COX-1-dependent
      PGE2 production but inhibited COX-2-dependent PGE2 production in a concentration
      dependent manner. The latter effect was found to be due to the inhibition of COX
      2 protein induction. These findings might explain the mechanism of the
      antirheumatic and anti-inflammatory activities of auranofin.

PMID- 9152413
TI  - Long-term non-progressive human immunodeficiency virus infection: new insights
      from the simian immunodeficiency virus model.

PMID- 9152414
TI  - Protection of monkeys vaccinated with vpr- and/or nef-defective simian
      immunodeficiency virus strain mac/human immunodeficiency virus type 1 chimeric
      viruses: a potential candidate live-attenuated human AIDS vaccine.
AB  - Two simian immunodeficiency virus strain mac (SIVmac)/human immunodeficiency
      virus type 1(HIV-1) chimeric viruses (SHIVs), designated NM-3 and NM-3n, with env
      derived from HIV-1 and defective vpr (plus defective nef for NM-3), were
      inoculated into seven macaques. These macaques were transiently or persistently
      infected and most of them produced long-lasting neutralizing antibodies and Env
      specific killer T cells to HIV-1 with no AIDS-like symptoms. When they were
      challenged with another SHIV with intact vpr and nef (designated NM-3rN), all
      were protected as judged by virus recovery, DNA detection by PCR and antibody
      responses. Anti-HIV-1 Env-specific killer T cells were considered to have played
      a major role in this protection, but a non-specific defence mechanism as well as
      specific immunity also appeared to be involved. Thus, these two non-pathogenic
      SHIVs induced long-lasting protective immunities in macaques, suggesting the
      possibility of gene-defective SHIVs as attenuated live vaccines for human use.

PMID- 9152415
TI  - A recombinant human adenovirus expressing the simian immunodeficiency virus Gag
      antigen can induce long-lived immune responses in mice.
AB  - Human adenovirus type 5 can be used as a vector to elicit immune responses to
      antigens expressed from heterologous DNA sequences incorporated into the viral
      genome, for example in mice immunized intraperitoneally. We have used a
      recombinant adenovirus which expresses the p55gag antigen of simian
      immunodeficiency virus to evaluate the nature and longevity of the response
      elicited when administered to mice by alterative routes which translate more
      readily to larger animals and man. In C57BI/6 mice immunized orally with a single
      dose of virus, a majority of the animals which showed evidence of responding to
      the immunogen by producing an anti-adenovirus response also produced a plasma
      antibody response to Gag which persisted for more than 1 year and a Gag-specific
      cytotoxic T cell response that could be detected for at least 6 months. In a
      minority of similarly immunized responding animals, only a cytotoxic response to
      Gag was observed although both humoral and cellular responses to adenovirus
      antigens were seen; intranasal immunization produced a Gag-specific response
      similar to this latter pattern. These findings suggest that delivery of
      adenovirus recombinants orally or intranasally may be a useful strategy for
      eliciting long-term cytotoxic T cell memory responses in splenocytes to candidate
      vaccine antigens.

PMID- 9152416
TI  - Modulation of primary human immunodeficiency virus type 1 envelope glycoprotein
      mediated entry by human antibodies.
AB  - Recently, we and others have shown that the interaction between envelope specific
      antibodies and primary human immunodeficiency virus type 1 (HIV-1) isolates may
      result in either inhibition or enhancement of virus entry. The outcome proved to
      be determined by the virus isolate rather than by the specificity of the
      antiserum used. To study the mechanism underlying this phenomenon, a series of
      HIV-1 envelope glycoproteins from closely related primary virus isolates of
      different syncytium inducing phenotypes, together with chimeras of these
      proteins, were tested in an envelope trans-complementation assay for their
      sensitivity to either antibody mediated inhibition or enhancement of HIV-1 entry.
      Based on the observation that, in contrast to the inhibition of HIV-1 entry,
      antibody mediated enhancement was not temperature dependent and could not be
      mediated by F(ab) fragments, we concluded that the mechanisms underlying these
      phenomena are different and that antibody mediated enhancement of HIV-1 entry is
      largely if not exclusively mediated by HIV-1 glycoprotein cross-linking. The
      susceptibility of the envelope glycoprotein chimeric viruses to neutralization or
      enhancement of infectivity proved to be primarily determined by the configuration
      of the V3 loop, and the affinity of the antibodies to monomeric HIV-1 gp 160
      molecules, proved to be of quantitative importance only. One human monoclonal
      antibody directed against gp41 (IAM 2F5) inhibited entry of all the viruses
      studied, irrespective of their phenotype, and directly proportional to its
      affinity to monomeric HIV-1 gp 160.

PMID- 9152417
TI  - AZT inhibits the transmission of human T cell leukaemia/lymphoma virus type I to
      adult peripheral blood mononuclear cells in vitro.
AB  - The effect of 3'-azido-3'-deoxythymidine (AZT) on in vitro infection of
      peripheral blood mononuclear cells (PBMCs) isolated from normal adult individuals
      with human T cell leukaemia/lymphoma virus type I (HTLV-I) was evaluated.
      Different PBMC samples were exposed to HTLV-I by cocultivation with MT-2 (a
      chronically infected cell line) in the presence of 20 U/ml of human recombinant
      interleukin 2 (IL-2) and graded concentrations of AZT. Control and drug-treated
      cultures, of both infected and uninfected PBMCs, were then grown for several
      weeks and monitored for virological and immunological parameters. The results
      showed a concentration-dependent anti-proliferative effect of AZT in both
      infected and non-infected cultures. Production of both proviral DNA and viral RNA
      was inhibited not only at the higher concentrations of AZT (8 microM and 32
      microM) but also at concentrations as low as 0.1-2 microM. These results were
      confirmed by PCR and by flow cytometry analysis for the viral core protein p19.
      Moreover, treatment with AZT resulted in a decreased expression of CD25 in
      cultures exposed to HTLV-I as well as in non-infected PBMCs. On the other hand,
      HLA-DR was down-regulated to a greater extent in drug-treated, virus-exposed
      cultures in comparison with those not infected. No evidence of the antiviral
      activity of AZT was observed in PBMC cultures already infected by HTLV-I or in MT
      2 cells. These findings demonstrate that treatment with AZT, when given at the
      time of infection with HTLV-I, has a marked protective effect on PBMCs.

PMID- 9152418
TI  - Molecular epidemiology of type 1 polioviruses from Africa.
AB  - The genetic relationships between type 1 polioviruses circulating in sub-Saharan
      Africa during the past decade have been investigated by partial genomic
      sequencing across the VP1/2A region of the polioviral genome. Sequencing
      templates were generated by single-step reverse transcription PCR amplification
      of the viral RNA using poliovirus-specific primers. Seven poliovirus genotypes,
      circulating in different geographical regions during different periods, were
      identified. Considerable genetic variation was exhibited by strains within
      several of these genotypes, indicative of sustained endemic transmission within
      individual countries. Two genotypes appear to be circulating in Africa at
      present; one major genotype, which has been in circulation since at least 1980,
      covers a wide geographical region and includes countries in western, central and
      southern Africa. Within this genotype are several smaller clusters, possibly
      representing strains in the process of evolving into new genotypes. The second
      genotype presently in circulation has been found only in Tanzania and Zambia to
      date, associated with a relatively small number of cases. Imported genotypes,
      introduced from the Middle East and the Indian subcontinent, have also recently
      been in circulation in eastern and central Africa. In South Africa, three
      genotypes, one unique to the country and the others imported from west Africa and
      the Middle East, co-circulated endemically between 1980 and 1985. A fourth
      genotype, introduced from countries to the north, displaced the endemic strains
      and continued to circulate until 1989. This study has generated a meaningful
      overview of the endemic circulation and regional transmission of type 1
      polioviruses throughout sub-Saharan Africa.

PMID- 9152419
TI  - Duration of the foot-and-mouth disease virus antibody response in mice is closely
      related to the presence of antigen-specific presenting cells.
AB  - Natural and experimental hosts infected with foot-and-mouth disease virus (FMDV)
      develop a long-lasting immune response that is closely related to the presence of
      anti-FMDV antibodies (Ab). We show here that spleen cells from animals which had
      been infected 3 or more months previously induced an anti-FMDV-Ab response in
      untreated animals which lasted more than 210 days after cell transfer.
      Persistence of infectious virus was excluded since virus isolation or detection
      of the viral genome by PCR in donor splenocytes were consistently negative. The
      role of antigen presentation (AP) in this phenomenon was studied in vivo by using
      irradiated splenocytes from virus-sensitized donor mice. Although these
      irradiated cells were unable to induce anti-FMDV-Ab in normal or irradiated
      recipient mice, they elicited a strong secondary reaction in FMDV-pre-sensitized
      recipients. The presence of AP cells (APC) presenting FMDV epitopes (FMDV/APC)
      was also analysed in mice sensitized to FMDV in different ways. A close
      correlation between FMDV/APC and the presence of anti-FMDV-Ab was found in
      infected mice as well as in mice immunized with different doses of inactivated
      virus, with or without adjuvants. Experiments in vivo and in vitro showed that
      the APC activity can be specifically blocked with either anti-MHC class II
      monoclonal antibody or anti-FMDV antiserum, and is dependent on the presence of T
      cell function. These results strongly suggest that persistent FMDV/APC are
      responsible for the existence and maintenance of an anti-virus immune response
      regardless of the immunization method used.

PMID- 9152420
TI  - Identification of a protein linked to the genomic and subgenomic mRNAs of feline
      calicivirus and its role in translation.
AB  - 125I protein labelling of oligo(dT)-selected RNA from feline calicivirus (FCV)
      infected cells revealed that the genomic and 2.4 kb subgenomic RNAs of FCV are
      linked to a 15 kDa protein (VPg). Proteinase K treatment of FCV RNA, to remove
      VPg, led to a decrease in the translatability of the RNA, but there was no
      obvious change in the site of RNA initiation. Addition of the cap analogue 7
      methylGTP to in vitro translations had no effect on the translation of FCV RNA,
      suggesting that FCV RNA is translated by a cap-independent mechanism. Further
      evidence that FCV RNA is translated by an unusual mechanism was obtained by
      translating FCV RNA in vitro at a range of K+ concentrations. FCV RNA was able to
      direct translation at K+ concentrations at which cellular RNA translation was
      inhibited.

PMID- 9152421
TI  - Characterization of the immune response of cattle against non-cytopathic and
      cytopathic biotypes of bovine viral diarrhoea virus.
AB  - Cross-infection studies of normal calves infected with homologous pairs of non
      cytopathic and cytopathic bovine viral diarrhoea virus (BVDV) showed significant
      differences in both humoral and cell-mediated immune responses against either
      biotype over a period of 5 months. Serological assays after primary intranasal
      inoculation showed striking significant (P < 0.05) differences between biotypes.
      Neutralizing titres were detected earlier and were much higher with the non
      cytopathic strain than with the homologous cytopathic strain. Significant biotype
      specific differences were also observed in the lymphocyte proliferative responses
      of cattle following in vitro stimulation by non-cytopathic/cytopathic BVDV and
      the non-structural p80 protein (NS3). The secondary immune response seems to be
      largely influenced by the biotype used for the primary inoculation and only to a
      lesser extent by the biotype inoculated for the second time after an interval of
      91 days. Animals exposed twice to the cytopathic biotype, which exhibited the
      lowest antibody titres, showed evidence of BVDV-specific cell-mediated immunity
      as measured by lympho-proliferation against BVDV. In contrast, the antibody
      response in the subgroup of animals inoculated twice with homologous non
      cytopathic virus was inversely correlated with the proliferative responses. These
      differences in the immune response were not readily apparent for the two other
      remaining subgroups which had received cytopathic or non-cytopathic biotypes
      alone following the second inoculation with non-cytopathic or cytopathic viruses,
      respectively. Taken together, these data suggest that the differences in immune
      responses against cytopathic or non-cytopathic strains may be due to a Th1/Th2
      like regulatory mechanism.

PMID- 9152422
TI  - Infectious cDNA clones of tick-borne encephalitis virus European subtype
      prototypic strain Neudoerfl and high virulence strain Hypr.
AB  - Infectious cDNA clones of two strains of tick-borne encephalitis (TBE) virus,
      i.e. European subtype prototypic strain Neudoerfl and the closely related but
      more virulent strain Hypr, were constructed. The recombinant constructs consisted
      of cDNAs stably inserted into the bacterial plasmid pBR322 under the control of
      T7 promoter elements. The genome of TBE virus strain Neudoerfl was successfully
      cloned, both as a full-length cDNA and as two partial cDNAs. In the case of
      strain Hypr, the genome is represented by two cDNA clones corresponding to the 5'
      and 3'-terminal halves of the genome. Highly infectious RNAs can be produced
      from the full-length cDNA clone or from the partial clones ligated in vitro to
      form full-length cDNA templates prior to T7 transcription. The biological
      properties of the recombinant progeny viruses, including virulence
      characteristics, were indistinguishable from the corresponding parent virus
      strains. Thus, the described infectious cDNA clones represent a useful and
      reliable experimental system for the specific mutagenesis of TBE virus.

PMID- 9152423
TI  - Binding of the influenza virus NS1 protein to model genome RNAs.
AB  - We have previously shown that the influenza virus NS1 protein exhibits stable
      binding to a model mini vRNA which is stronger than its binding to dsRNA. In this
      study, we confirmed that the binding depended on a higher-order structure of the
      model RNA, probably the panhandle structure formed by pairing between the 5'- and
      3'-terminal common sequences. The formation of the structure was enhanced by the
      NS1 protein itself. We propose that an A bulge in a stretch of double helix
      results in a binding site with greater affinity for the NS1 protein.

PMID- 9152424
TI  - Mapping of the target antigens of the rotavirus-specific cytotoxic T cell
      response.
AB  - The cytotoxic T cell (CTL) response in C57/B16 (H-2b) mice to rotavirus has been
      analysed using a cognate set of vaccinia virus recombinants covering the 12
      primary gene products of the UKtc strain of bovine rotavirus. The gene products
      of RNA segments 5 (VP5/NSP-1) and 8 (VP7) both elicited a classic CD8+ Class I
      MHC restricted CTL response. Using L cells transfected with specific Class I MHC
      loci as targets the VP5/NSP-1 response was found to be restricted at Db and the
      VP7 response at Kb. Vaccinia virus recombinants expressing VP7 genes from seven G
      serotypes were used to show that the CTL response to this antigen is completely
      cross-reactive. By contrast, using the same strategy the CTL response to VP5/NSP
      1 was found to be virus strain specific. A vaccinia virus recombinant carrying
      RNA segment 5 from the deletion mutant P9D delta 5 was used to localize at least
      one CTL epitope in VP5/ NSP-1 to the first 150 amino acids of the protein. The
      expression of a number of fragments of VP7 in vaccinia virus recombinants was
      used to show that the CTL epitope (amino acids 31-40) previously identified
      through the use of synthetic peptides is virus serotype specific rather than
      cross-reactive.

PMID- 9152425
TI  - Characterization of tubular structures composed of nonstructural protein NS1 of
      African horsesickness virus expressed in insect cells.
AB  - The characteristic tubules that are produced during the orbivirus infection cycle
      are composed of a major viral nonstructural protein, NS1. To characterize the NS1
      gene and gene product of African horsesickness virus (AHSV), a full-length cDNA
      copy of the NS1 gene of AHSV-6 was cloned and the nucleotide sequence determined.
      NS1 was highly conserved within the AHSV serogroup with between 95-98%
      conservation of amino acids among NS1 of AHSV-6, AHSV-4 and AHSV-9. The structure
      of AHSV NS1 tubules was investigated by in vitro translation of the AHSV-6 NS1
      gene followed by expression of the gene in insect cells. The NS1 protein
      assembled in tubular structures with a diameter of approximately 23 nm and
      lengths of up to 4 microns. The absence of a ladder-like structure and lower
      sedimentation value of AHSV NS1 tubules clearly distinguished them from those of
      bluetongue virus.

PMID- 9152426
TI  - Hepatitis B virus preS1 functions as a transcriptional activation domain.
AB  - Hepatitis B virus (HBV) preS1 fused to the GAL4 DNA-binding domain functioned as
      a transcriptional activation domain in yeast and mammalian cells. The GAL4-preS1
      fusion proteins derived from the preS1 of all three tested HBV subtypes (adr, adw
      and ayw) specifically activated the transcription of a lacZ or chloramphenicol
      acetyltransferase reporter gene linked to a GAL4-responsive promoter in transient
      transfection assays using yeast or HepG2 cells, respectively. Deletion analyses
      showed that the segments of preS1 from residues 21 to 90 and from residues 21 to
      56 are sufficient and essential for the activity, respectively. Stable expression
      of GAL4-preS1 in Chinese hamster ovary cells also produced transactivator
      activity. These results suggest that preS1 fused to any DNA-binding domain of
      transcription factors would have transactivation potential.

PMID- 9152427
TI  - Presence of a novel hamster oral papillomavirus in dysplastic lesions of hamster
      lingual mucosa induced by application of dimethylbenzanthracene and excisional
      wounding: molecular cloning and complete nucleotide sequence.
AB  - A combination of 9,10-dimethyl-1,2-benzanthracene (DMBA) application and
      excisional wounding on the lingual tips of Syrian Golden hamsters (Mesocricetus
      auratus) induces dysplastic and malignant mucosal lesions. Papillomavirus genus
      specific antigen and viral particles, measuring 55 nm in diameter, were
      demonstrated in the nuclei of squamous cells of dysplastic lesions showing
      koilocytotic change. In this study, we cloned a circular genome at a single Kpnl
      site from one of these dysplastic lesions. The genomic sequence of this clone,
      consisting of 7647 bp, was shown to be that of a novel papillomavirus with a
      conserved genomic organization. We named the new virus hamster oral
      papillomavirus (HOPV). All dysplastic lesions induced by this combination of DMBA
      application and excisional wounding contained viral DNA. Although Southern blot
      hybridization analysis could not detect the HOPV genome, PCR analysis
      demonstrated the latent HOPV genome in the tongue and skin of an untreated
      hamster. These results suggest that latently present HOPV genome is reactivated
      by the DMBA/wounding procedures. Lingual HOPV infection may be an important model
      for gaining insight into the interactions between papillomavirus infection,
      chemical carcinogens and physical irritations in carcinogenesis or malignant
      transformation.

PMID- 9152429
TI  - Localization of latency-associated transcripts in the uterovaginal plexus of
      herpes simplex virus type 1 and 2 latently infected mice.
AB  - The vagina and medulla of the adrenal gland of mice vaginally infected with
      herpes simplex virus (HSV) types 1 and 2 were examined in the latent stage of
      infection (5 to 51 weeks post-infection). RNA in situ hybridization with HSV-1
      and -2 latency-associated transcript (LAT) RNA probes resulted in positively
      stained neuronal cell nuclei in the uterovaginal plexus, but not in the medulla
      of the adrenal gland. These organs were chosen because HSV antigens can be
      detected not only in the vaginal epithelium, but also in neurons of the
      uterovaginal plexus and in the medulla of the adrenal gland at the acute stage of
      genital infection. To our knowledge, this is the first report describing LATs in
      neurons of the uterovaginal plexus in the genital tract of latently HSV-infected
      mice.

PMID- 9152428
TI  - The link between integration and expression of human papillomavirus type 16
      genomes and cellular changes in the evolution of cervical intraepithelial
      neoplastic lesions.
AB  - We have matched a PCR assay which detects disruptions in the E2 reading frame of
      human papillomavirus type 16, with RNA in situ hybridization patterns and shown
      that in 15 out of 16 cervical intraepithelial neoplastic (CIN) III lesions and in
      19 out of 19 tumours, the E2 gene is disrupted with no detectable E2 transcripts.
      Varying levels of E6-E7 transcripts are detected in CIN III lesions, with
      stronger signals in tumours. The cytokeratin profile of most tumours: cytokeratin
      10-, 14- and 19-positive and 4-, 13- and 18-negative, is also detected in CIN III
      lesions. The changes in levels of alpha 2, beta 1 and beta 4 integrins, CD44 and
      E-cadherin occur during the evolution of high-grade CIN lesions. Increases in the
      levels of expression of CD44 and E6-E7 transcripts, coupled with changes in the
      cellular localization of the Notch protein, define the transition from CIN III
      lesions to tumours.

PMID- 9152430
TI  - Equine herpesvirus 4 DNA in trigeminal ganglia of naturally infected horses
      detected by direct in situ PCR.
AB  - Neuronal and lymphoid tissues of 15 randomly selected horses were analysed post
      mortem by liquid nested-PCR to study the tropism of equine herpesvirus 4 (EHV-4).
      In four animals the trigeminal ganglia and in one case the lung were positive.
      Using a direct in situ PCR the EHV-4 genome was localized in the nuclei of
      neurons and in the bronchiolar as well as alveolar epithelium of the lung. In
      none of these tissues could infectious virus or viral antigens be detected.
      Applying the more sensitive liquid RT-PCR, however, an acute infection was
      demonstrated in one of the trigeminal ganglia by amplification of viral
      transcripts coding for glycoprotein B. The failure to detect these transcripts in
      the other trigeminal ganglia and the lung indicates a latent infection. This
      report formally proves that, like other members of the Alpha-herpesvirinae, EHV-4
      establishes latency in the trigeminal ganglia.

PMID- 9152431
TI  - Detection and distribution of equine herpesvirus 2 DNA in the central and
      peripheral nervous systems of ponies.
AB  - The distribution of equine herpesvirus 2 (EHV-2) DNA within neurological and
      lymphoid tissues from 12 EHV-2 seropositive Welsh mountain ponies was determined
      by PCR. The lymphoid sites sampled in this study were almost universally PCR
      positive, thus confirming the existing virus co-cultivation data which suggest
      that the lymph nodes draining the respiratory tract are the main reservoirs of
      EHV-2 DNA. In addition, EHV-2 DNA was also detected, albeit with lower frequency,
      within both the peripheral and central nervous systems (PNS and CNS) of these
      animals. Of the CNS sites sampled 11% were PCR-positive and in the PNS the
      trigeminal ganglion proved PCR-positive in 50% of the animals tested. Since the
      nasal epithelium is innervated by the maxillary division of the trigeminal nerve,
      these observations suggest that the trigeminal ganglion may represent a
      biologically important site for EHV-2 latency.

PMID- 9152432
TI  - Transmission of equine herpesvirus 2 to the mouse: characterization of a new
      laboratory infection model.
AB  - Intranasal inoculation of BALB/c mice with a recent clinical isolate of equine
      herpesvirus 2 (EHV-2 strain MR) produced a productive infection characterized by
      clinical signs, including weight-loss and conjunctivitis, but no mortality.
      Infectious virus was isolated from the lung, trachea and nasal turbinates with
      the highest titres present in lung tissue; EHV-2 neutralizing antibody was
      detected in the serum on day 21 post-inoculation. No infectious virus was
      detected in neural tissue, blood or lymphoid tissues. An EHV-2-specific nested
      PCR confirmed the presence of EHV-2 DNA in the respiratory tissues. In addition,
      EHV-2 DNA was detected in the trigeminal ganglia and olfactory bulbs from the
      first day after inoculation and these tissues remained positive for EHV-2 DNA for
      at least 30 days, by which time EHV-2 DNA had been cleared from all other
      tissues.

PMID- 9152433
TI  - Stringent structural and sequence requirements of the human herpesvirus 6B lytic
      phase origin of DNA replication.
AB  - The lytic-phase origin of DNA replication from human herpesvirus 6B (HHV-6B
      oriLyt) contains two binding sites for the origin-binding protein (OBPH6B), both
      of which are required for DNA replication and which are separated by an AT-rich
      spacer. We have tested the functional significance of the structural, spatial and
      sequence characteristics of this spacer element by constructing a series of
      mutated origin sequences and analysing their replication efficiency. Changes in
      the sequence composition of length of the spacer resulted in dramatic decreases
      in replication efficiency. Furthermore, in contrast to what has been observed for
      herpes simplex virus type 1 (HSV-1) oriS, insertion of a complete helical turn of
      DNA into the spacer also resulted in abrogation of origin function. These data
      suggest that the arrangement of OBP sites in HHV-6B oriLyt is stringently
      constrained in terms of spacing and intervening sequence.

PMID- 9152434
TI  - Antigenic analysis of human herpesvirus 7 (HHV-7) and HHV-6 using immune sera and
      monoclonal antibodies against HHV-7.
AB  - Using polyclonal and monoclonal (MAbs) antibodies to human herpesvirus 7 (HHV-7),
      we have studied HHV-7-specific polypeptides. Human sera were obtained during the
      convalescent phase from patients with exanthem subitum due to HHV-7, and at least
      16 HHV-7-specific polypeptides with apparent molecular masses of 26-210 kDa were
      immuno-precipitated. Sera prepared in mice also precipitated at least 17 HHV-7
      specific polypeptides with molecular masses of 26-210 kDa. Among them, the most
      commonly observed antigenic protein had an apparent molecular mass of 52 kDa.
      Forty-two clones secreting MAbs against HHV-7-specific proteins, as determined by
      immunofluorescence assays, were established from BALB/c mice immunized with HHV-7
      infected cell extracts. Seven MAbs which immunoprecipitated HHV-7-specific
      polypeptides were further characterized. Two of these, MAbs 5E12 and 5F12,
      reacted predominantly with glyco-proteins of 78 kDa and 85 kDa, respectively, and
      possessed neutralizing activity. This suggests that there are at least two
      neutralization-inducing proteins in HHV-7. MAb 16B4 reacted with the major
      immunogenic protein of 52 kDa. Five of the 42 MAbs also reacted in
      immunofluorescence assays with HHV-6 antigens to the same degree as to HHV-7. Two
      other MAbs, 7C10 and 10F1, recognized an HHV-7 protein of 40 kDa, and only 7C10
      cross-reacted with an HHV-6 protein of 45 kDa.

PMID- 9152435
TI  - Particle and genomic characteristics of a new member of the Ascoviridae:
      Diadromus pulchellus ascovirus.
AB  - A new member of the family Ascoviridae, Diadromus pulchellus ascovirus (DpAV),
      has been found in the lepidopteran nymphs of Acrolepiopsis assectella parasitized
      by the hymenopteran wasp Diadromus pulchellus. Virions have the standard features
      of the ascovirus group; each particle is about 220 nm long and 150 nm wide. They
      are multilayered, with two clear 7-nm-thick outer layers and one 15-nm-thick
      inner layer surrounding an electron-dense core (155 x 110 nm). However, the
      flattened rice-grain shape and fragility of the DpAV particles are unlike that of
      known ascoviruses infecting Noctuidae species. They form large vesicles
      containing virions in infected cells. The DpAV genome is about 116 kb long and
      has a circular and relaxed structure. It contains 6-8 repeated and interspersed
      sequences of 494 bp. The structural and genomic features of DpAV suggest that
      this virus belongs to an ascovirus sub-family different from that containing the
      ascoviruses previously found to infect species of Noctuidae (Federici et al.,
      1991).

PMID- 9152436
TI  - Biological and molecular features of the relationships between Diadromus
      pulchellus ascovirus, a parasitoid hymenopteran wasp (Diadromus pulchellus) and
      its lepidopteran host, Acrolepiopsis assectella.
AB  - The Diadromus pulchellus ascovirus (DpAV) has been isolated from laboratory
      strains of Diadromus pulchellus and in natural wild populations collected from
      the Antibes locality (southern France). The DpAV genome was found in the cells of
      the head, thorax and abdomen of this hymenopteran wasp. DpAV virions are present
      in the female genitalia and are transmitted to the nymphal lepidopteran host,
      Acrolepiopsis assectella, at each oviposition of the female wasp. The presence of
      the DpAV genome in all Diadromus somatic cells suggests that it is inherited by
      vertical transmission. DpAV is amplified in the host tissues during the larval
      development of D. pulchellus in A. assectella. Cell lysis due to amplification of
      the virus does not prevent the development of the hymenopteran larva. Virus
      amplification appears to be slower in nymphs parasitized by D. pulchellus than in
      nymphs artificially infected with DpAV alone. Lysis of the nymphal cells due to
      viral replication seems to be synchronous with egg hatching and the development
      of the hymenopteran larva. The features of DpAV and its relationship with the
      parasitoid wasp D. pulchellus during its development are compared to those of the
      ichnoviruses.

PMID- 9152437
TI  - Nucleotide sequence and taxonomy of maize chlorotic dwarf virus within the family
      Sequiviridae.
AB  - The complete sequence of a Tennessee isolate of maize chlorotic dwarf virus (MCDV
      TN) was determined from cDNA clones and by direct sequencing of the viral RNA.
      The genome is 11813 nucleotides (nt) in length and contains one large open
      reading frame between nt 435 and 10763 that encodes a polyprotein of 3443 amino
      acids. The N-terminal amino acid sequences were determined for the three capsid
      proteins. All three were adjacent, starting at nt 2526 and putatively ending at
      nt 3761. Comparison of the sequence of MCDV-TN with other viral sequences
      revealed similarities to several plant picorna-like viruses including members of
      the Sequiviridae, Comoviridae and Potyviridae. This work also provides evidence
      based on genome organization that MCDV-TN is a member of the genus Waikavirus
      within the family Sequiviridae.

PMID- 9152438
TI  - Subcellular localization of the 28 kDa protein of the triple-gene-block of bamboo
      mosaic potexvirus.
AB  - Open reading frame 2 of the bamboo mosaic potexvirus (BaMV) genome encodes a 28
      kDa protein, the first of the "triple-gene-block' of BaMV which is believed to
      play a role in cell-to-cell movement of the virus in host plants. The 28 kDa
      protein was expressed in Escherichia coli and polyclonal antiserum was raised in
      a rabbit. Western blot analyses showed that the 28 kDa protein was associated
      mainly with components in the cell wall and 30000 g pellet fractions of a BaMV
      infected leaf homogenate. Immunogold electron microscopy of infected leaf tissues
      revealed that the 28 kDa protein was associated with electron-dense crystal-line
      bodies (EDCBs) in the cytoplasm and nuclei. Nuclear EDCBs were found closely
      associated with nucleoli. Gold-labelled EDCB-like structures were also detected
      in the cytoplasm, but not within nuclei, in protoplasts up to 48 h post
      inoculation. No specific labelling of the 28 kDa protein was found within any
      cytoplasmic structures or within cell walls.

PMID- 9152439
TI  - Plasmid vector for cloning infectious cDNAs from plant RNA viruses: high
      infectivity of cDNA clones of tomato aspermy cucumovirus.
AB  - An improved version of the previously obtained cloning vector pCass was
      constructed by partially duplicating the 35S promoter used to drive the transient
      transcription of cloned viral cDNAs. Full-length cDNAs of the three genomic RNAs
      of tomato aspermy cucumovirus (TAV) cloned in this improved pCass (designated
      pCass2) gave a 3-fold higher infectivity in two plant species tested than the
      same cDNAs cloned in pCass1 with only a single 35S promoter. Host range,
      symptoms, morphology of viral particles and viral progeny RNAs induced by these
      sets of infectious cDNA clones analysed were identical to those induced by the
      wild-type virus. A mutant of genomic TAV RNA 3 containing a 163 nt deletion in
      the 3' untranslated region was stably maintained in the progeny RNAs, indicating
      that these cDNA clones may facilitate a study of virus function. This is the
      first report of infectious cDNA clones of TAV as well as of infectious cDNA
      clones with a duplicated 35S promoter of CaMV.

PMID- 9152440
TI  - Evidence for an alternative direct route of access for the scrapie agent to the
      brain bypassing the spinal cord.
AB  - Scrapie is a disease which occurs naturally in sheep and goats and belongs to a
      group of neurodegenerative disorders known as transmissible spongiform
      encephalopathies, or TSEs. There is currently no cure for TSEs, and the causative
      agent has not yet been identified. Numerous experiments, however, have addressed
      the pathogenetic process following a TSE infection. In this paper we present a
      study of the spread of the scrapie agent after intraperitoneal infection of
      hamsters. The accumulation of TSE-specific amyloid protein, TSE-AP (also known as
      PrP), was used as a marker for infectivity. The data suggested three points of
      agent entry into the spinal cord: the most important one between thoracic
      vertebrae T7-9, and two minor ones in the lower cervical spinal cord and between
      vertebrae T13-L2. Further, strong evidence was found for the existence of a
      direct route of access to the brain which bypasses the spinal cord and most
      likely terminates in the medulla oblongata. The indication of an alternative
      pathway to the brain was confirmed by the data from orally infected hamsters. The
      spleen appeared to play a potential, but non-essential role in pathogenesis after
      intraperitoneal infection in our animal model.

PMID- 9152441
TI  - Back pain in the workplace. What you lift or how you lift matters far less than
      whether you lift or when.
AB  - In spite of more than 50 years of concerted effort to diminish task demand, the
      incidence of compensable back injuries has not wavered. Before we persist for
      another 50 years in the quest for the "right way to lift," we should consider
      recent multivariate clinical investigations that suggest alternative approaches.
      Because task context is at least as important as task content in this regard, it
      follows that including regional backache under the rubric of "compensable injury"
      demands reconsideration. Likewise, rather than pursuing the "right way to lift,"
      the more reasonable and humane quest might be for workplaces that are comfortable
      when we are well and accommodating when we are ill.

PMID- 9152442
TI  - Anatomic considerations of the lumbar isthmus.
AB  - STUDY DESIGN: A morphometric study of lumbar isthmus from L1 to L5 on 30 dried
      lumbar spines was conducted. OBJECTIVE: To provide anatomic data about the lumbar
      isthmus and to quantitatively evaluate structural features of the lumbar isthmus
      and its relationship to adjacent anatomic structures. SUMMARY OF BACKGROUND DATA:
      There are very few anatomic studies about the lumbar isthmus, and no study
      describes the relationship of the lumbar isthmus to its adjacent structures.
      METHODS: Direct measurements using digital calipers and a goniometer were taken
      from 30 dried lumbar spines. Anatomic evaluation focused on the lumbar isthmus
      and its related structures, the isthmus pedicle, and superior and inferior
      facets. Seven linear and four angular parameters of the lumbar isthmus were
      determined. RESULTS: The length of the superior edge of the isthmus gradually
      increased from L2 to L5 (from 8.22 +/- 1.43 mm at L2 to 10.44 +/- 1.90 mm at L5),
      and that of its inferior edge progressively decreased from L2 to L5 (from 8.67 +/
      1.76 mm at L2 to 6.34 +/- 1.74 mm at L5). The superoinferior diameter of the
      isthmus decreased from L3 to L5 (from 13.87 +/- 1.77 mm at L3 to 13.26 +/- 2.49
      mm at L5). The superior edge of the isthmus was the thinnest at L4 (1.62 +/- 0.58
      mm), and its thickness inferiorly increased from L1 to L5 (from 6.71 +/- 1.47 mm
      at L1 to 7.76 +/- 1.08 mm at L5). The medial and caudal inclination of the
      isthmus with respect to the pedicle gradually increased from L1 to L5 (from 112.3
      degrees +/- 13.8 degrees at L1 to 119.2 degrees +/- 11.2 degrees at L5 medial
      inclination and from 132.5 degrees +/- 8.8 degrees at L2 to 139.0 degrees +/-
      12.1 degrees at L5 caudal inclination, respectively). The dimensions of the
      lumbar isthmus were positively correlated to dimensions of the pedicle and
      orientations of the facets. CONCLUSIONS: This study provides detailed anatomic
      data of the lumbar isthmus. Anatomic parameters of the lumbar isthmus are related
      to the vertebral levels and have a significant correlation with the angles of the
      facets and the dimensions of the pedicles. The vulnerability of the pars
      interarticularis of the fifth lumbar vertebra has been anatomically confirmed.

PMID- 9152443
TI  - A model for chronic nerve root compression studies. Presentation of a porcine
      model for controlled, slow-onset compression with analyses of anatomic aspects,
      compression onset rate, and morphologic and neurophysiologic effects.
AB  - STUDY DESIGN: Compression onset rate, anatomic aspects, and morphologic and
      neurophysiologic effects in spinal nerve roots were studied in a nerve root
      compression model in pigs. OBJECTIVES: To analyze the compression onset rate by
      measuring the gradual reduction of the inner diameter of the constrictor, the
      motor nerve conduction velocity by electromyography, the morphologic changes by
      light microscopy, and the gross and vascular anatomy by dissection and ink
      injections, respectively, in a model for experimental chronic nerve root
      compression. SUMMARY OF BACKGROUND DATA: Chronic nerve root compression is
      recognized to be related to back pain syndromes, including sciatica. Various
      aspects of morphologic and physiologic changes have been studied previously in
      models for acute compression and chronic nerve root irritation, but a controlled,
      graded chronic nerve root compression model has not been described. METHODS: An
      ameroid constrictor was applied around a spinal nerve root just cranial to the
      dorsal root ganglion. The inner diameter of this constrictor gradually becomes
      reduced. After 1 week or 4 weeks, electromyographic measurements were performed,
      and tissue samples were harvested for histologic analyses. The gross and vascular
      anatomy of the pigs' spinal nerve roots were studied by dissection and ink
      injections. RESULTS: There was a statistically significant decrease in the nerve
      conduction velocity in compressed compared with noncompressed spinal nerve roots
      after 1 week and after 4 weeks. The ameroid constrictors induced nerve fiber
      damage, endoneural hyperemia, bleeding, and inflammation at the compression zone.
      There was often a severe reduction in the number of myelinated fibers after 4
      weeks. CONCLUSION: A model for controlled, chronic, partial nerve root injury
      using a gradual compression-onset constrictor is presented. This model allows for
      induction of a controlled graded chronic nerve root injury and can be used for
      research on basic pathophysiologic mechanisms and on the effects of various
      interventions on nerve root injury development.

PMID- 9152444
TI  - An experimental study of a combination method using a pedicle screw and laminar
      hook for the osteoporotic spine.
AB  - STUDY DESIGN: Using human cadaver spines, the authors compared the effect of
      using a combination of pedicle screw and laminar hook on the same vertebra with
      that of using a pedicle screw alone in reference to bone mineral density of the
      vertebra under nondestructive cyclic loading. OBJECTIVES: To quantify stiffness
      obtained by pedicle screw alone and by the combination method and to clarify a
      relationship between stiffness obtained by each instrumentation method and bone
      mineral density of the vertebra. SUMMARY OF BACKGROUND DATA: The use of pedicle
      screws apparently improves the union rate of spinal fusion. Instrumentation
      failures sometimes occur, however, such as loosening or loss of correction of the
      spine, especially in patients with osteoporosis. Some augmentation method in
      instrumentation is necessary to overcome bone fragility in the osteoporotic
      spine. METHODS: Thirteen cadaver lumbar vertebrae were used for this study. Bone
      mineral density was measured by dual-energy X-ray absorptiometer. After
      separating each vertebrae, the pedicle screw was screwed into a vertebra. Five
      cycles of cephalocaudal loading were performed to the shank of the screw with a
      cross-head speed of 3 mm/min under a maximum load control of 29.4 N using an
      Instron type testing machine, and the stiffness obtained with the pedicle screw
      (Kj) was calculated from the load-deformation curve. Then, a laminar hook was set
      and connected to the screw via a rod. Mechanical testing was performed in the
      same way, and the stiffness obtained with the combination method (Kf) was
      determined. Kj and Kf were compared using the paired t test. The relationship
      between Kj, Kf, or the stiffness improvement ratio ([Kf-Kj]/Kj) by the
      combination method and bone mineral density was analyzed by linear regression
      analysis. RESULTS: Stiffness obtained by the combination method was significantly
      greater than that obtained by pedicle screw alone (89.8 +/- 35.0 N/mm by the
      combination method, 60.2 +/- 19.6 N/mm by pedicle screwing alone; P < 0.0001).
      Stiffness, whether obtained by pedicle screw alone or by the combination method,
      was positively correlated with bone mineral density (with pedicle screw alone, R2
      = 0.614, P < 0.0001; with the combination method, R2 = 0.645, P < 0.0001).
      However, there was no significant correlation between stiffness improvement ratio
      and bone mineral density. CONCLUSION: Instrumentation stiffness obtained by the
      combination method was significantly greater than that obtained by the use of
      pedicle screw alone. There was no significant correlation between the improvement
      ratio by the combination method and bone mineral density. These results suggest
      that the combination method is valuable irrespective of the presence of spinal
      osteoporosis.

PMID- 9152445
TI  - Finite element analysis of cervical facetectomy.
AB  - STUDY DESIGN: Moment-rotation responses and disc anulus stresses of intact and
      facetectomized C4-C6 cervical spinal units were analyzed using detailed, three
      dimensional, finite element models. OBJECTIVES: To evaluate biomechanical effects
      of progressive unilateral and bilateral facet resections on cervical spine
      segmental mobility (external response) and disc anulus stress (internal
      response). SUMMARY OF BACKGROUND DATA: Experimental studies have demonstrated
      that facetectomy significantly increases segmental mobility of the cervical
      spine. The biomechanical effects of facetectomy on the internal response,
      however, have not been investigated. METHODS: Moment-rotation responses of C4
      with respect to C6 and von Mises stress in the disc anulus were examined using
      finite element models of a 0% (intact), 25%, 50%, 75%, and 100% unilaterally and
      bilaterally facetectomized cervical spinal unit. The model simulations were
      conducted under the pure-moment loading of 1.8 Nm in flexion, extension, lateral
      bending, and axial torsion. The intact model also was validated experimentally
      under the same conditions. RESULTS: The moment-rotation responses of the intact
      unit were within the ranges of experimental data. Cervical rotations increased
      with the increased degree of facet resection. The greatest change occurred
      between 50% and 75% facet resections in bilateral facetectomy. Similar patterns
      were found for disc anulus stresses, but to a greater extent. The maximum
      increase in rotation (11%) and in anulus stress (30%) occurred in lateral
      bending. Torsion was the least affected loading mode. The effects of unilateral
      facetectomy were considerably less than those of 75% bilateral facetectomy.
      CONCLUSIONS: Facetectomy has a greater effect on anulus stress than on
      intervertebral joint stiffness. Significant increase in anulus stresses and
      segmental mobility may occur when bilateral facet resection exceeds 50%.

PMID- 9152446
TI  - Wire fixation techniques of the cervical facets.
AB  - STUDY DESIGN: The changes in the biomechanical responses of the cervical spine
      altered by multilevel laminectomy to various facet wiring techniques were
      evaluated. OBJECTIVE: To determine the effectiveness of various proposed
      techniques of cervical facet wiring used to offer rigid internal fixation after
      multilevel laminectomy. METHODS: Eight human cadaveric spine segments from C2-11
      underwent combined flexion-compression loading. After testing intact and three
      level laminectomy (C4-C6) preparations, two techniques of facet wiring fixation
      were evaluated in an identical manner. Force, displacement, and kinematics data
      at every level of the column were obtained. RESULTS: The mean stiffness of the
      intact column was significantly greater than the mean stiffness for
      laminectomized specimens. Individual facet wiring to the bone graft and through
      the spinous process below the laminectomy failed to restore stiffness to the
      laminectomized preparations, whereas the Luque rectangle method restored the
      stiffness to that found in the intact column. The increases in segmental and
      overall sagittal rotations resulting from multilevel laminectomy were not
      decreased significantly by the individual facet wiring technique, but the Luque
      rectangle technique demonstrated a reduction of sagittal rotations compared with
      laminectomy without fixation. CONCLUSIONS: The significant increases in total
      column flexibility and segmental flexural rotations after multilevel laminectomy
      were not corrected by techniques that depend on individual facet wires secured to
      an overlying strut, including wiring to the inferior intact segment. Crosslinking
      of the facet wire fixation above and below the laminectomized segments, as
      exemplified by the Luque rectangle technique, restored column stiffness and
      reduced segmental sagittal rotations.

PMID- 9152447
TI  - Cervical pedicle screws versus lateral mass screws. Anatomic feasibility and
      biomechanical comparison.
AB  - STUDY DESIGN: Biomechanical comparison of the pull-out strengths of lateral mass
      and pedicle screws in the human cervical spine. Measurements of pedicle
      dimensions and orientation were compiled. OBJECTIVES: To determine if
      transpedicular screws provide greater pull-out resistance than lateral mass
      screws and to investigate the anatomic feasibility of pedicle screw insertion.
      SUMMARY OF BACKGROUND DATA: Cervical pedicle screws have been reported in limited
      clinical and biomechanical studies, and some quantitative cervical pedicle
      anatomy has been reported. No direct biomechanical comparisons have been made
      between lateral mass and pedicle screws. METHODS: Fifty-six fresh disarticulated
      human vertebrae (C2-C7) were evaluated with computed tomography to determine
      morphometry and vertebral body bone density. Lateral mass and pedicle screws were
      randomized to left versus right. A 3.5-mm cortical screw was used for both
      techniques, unless a pedicle was narrower than 5.0 mm; then a 2.7-mm cortical
      screw was used instead. Pedicle wall violations were recorded. Screws were
      subjected to a uniaxial load to failure. Mean pedicle height, width, and angle
      with respect to the vertebral midline were tabulated for each level. RESULTS: The
      mean load-to-failure was 677 N for the cervical pedicle screws and 355 N for the
      lateral mass screws. No significant correlations for either screw type were found
      between pull-out strength and bone density, screw length, or vertebral level.
      Pedicle and lateral mass dimensions were highly variable and not predictive of
      pull-out strength. Seven (13%) minor pedicle wall violations were observed.
      CONCLUSIONS: Cervical pedicle screws demonstrated a significantly higher
      resistance to pull-out forces than did lateral mass screws. The variability in
      pedicle morphometry and orientation requires careful preoperative assessment to
      determine the suitability of pedicle screw insertion.

PMID- 9152449
TI  - Prediction of success from a multidisciplinary treatment program for chronic low
      back pain.
AB  - STUDY DESIGN: The study included 90 disabled patients with chronic low back pain
      recruited from a pain clinic who were admitted to an 8-week program of functional
      restoration and behavioral support. Initial evaluations included a medical
      examination, rating of the physical impairment, a personal interview, a visual
      analogue scale to record pain intensity, an assessment of limitations for daily
      activities, a pain disability index, a depression and psychovegetative scale, and
      a scale to evaluate general living standards. The physical assessment included
      different flexibility measurements, measurement of power and endurance through
      standardized exercises, and measurements of isokinetic trunk and lifting strength
      and general endurance. The measurements were repeated at the end of the 8-week
      program and thereafter an intervals of 6 and 12 months. Final analyses were
      carried out on 82 patients. OBJECTIVES: To determine whether objective or
      subjective signs most influence the outcome of rehabilitation. SUMMARY OF
      BACKGROUND DATA: In recent years, several studies have shown that active and
      intensive multimodal treatment of chronic low back pain is successful. Until now
      there has been lack of information about which patients will respond to the
      therapy and what is the most effective part of treatment. METHODS: Prognostic
      factors (return to work, pain intensity, self-assessment of treatment success by
      patients) were tested by studying variance and regression analyses for their
      ability to predict treatment outcome. RESULTS: Certain factors were identified
      that had a significant impact on determining the probability of a patient's
      return to work and the reduction of pain intensity. These factors included self
      evaluation for predicting a return to work, the length of absence from work,
      application for pension, and a decrease is disability after treatment. Overall
      satisfaction with treatment was best determined by the number of medical
      consultations before treatment, the extent of disability, previous measures taken
      for coping with the disease, and reduction of disability during treatment.
      Medical background, medical diagnosis, and physical impairment had no predictive
      value. Physical variables (i.e., mobility, strength, endurance, and physical
      performance) also demonstrated only limited predictive value. CONCLUSION: This
      study has demonstrated that the most important variable in determining a
      successful treatment of chronic low back pain is the reduction of subjective
      feelings of disability in patients.

PMID- 9152448
TI  - The cervical spine in Marfan syndrome.
AB  - STUDY DESIGN: Prospective radiographic and clinical analysis of a consecutive
      unselected population of persons with Marfan Syndrome. OBJECTIVES: To determine
      cervical spine abnormalities present in the Marfan population compared with that
      seen in the general population. SUMMARY OF BACKGROUND DATA: In the treatment of a
      large population of patients with Marfan Syndrome, three serious cervical spine
      disorders were noted. To the authors' knowledge, no report of cervical
      abnormalities in patients with Marfan Syndrome exists in the literature.
      Therefore, the cervical spine in these patients was studied in a systematic
      fashion. METHODS: An unselected group of 104 consecutive patients with Marfan
      Syndrome seen at a medical genetics follow-up examination underwent lateral
      neutral and flexion-extension cervical spine radiographs. Parameters of
      alignment, size, and stability were measured. Patients with Marfan Syndrome aged
      35-45 years and matched controls were given a pain questionnaire to complete.
      RESULTS: The prevalence of focal kyphosis was 16%. A large number of patients
      with Marfan Syndrome (54%) had increased atlantoaxial translation. The
      preadolescent Marfan population has a greater range of motion than either the
      adolescent or adult populations. The Marfan population has an increased
      radiographic prevalence of basilar impression (36%), and the odontoid height
      (3.69 +/- 0.53 cm) was larger than reported norms (2.34 +/- 0.22 cm). Cervical
      stenosis was rare, with 3% having a critical Torg ratio at C3 and 2% having a
      critical Torg ratio at C6. Neck pain frequency did not differ significantly from
      that of age-matched controls. CONCLUSION: Based on the increased prevalence of
      several cervical bony and ligamentous abnormalities, patients with Marfan
      Syndrome were recommended to avoid sports with risks of high-impact loading of
      the cervical spine. Given the rarity of actual neurologic injuries in the Marfan
      population, however, radiographs for all patients with Marfan Syndrome undergoing
      general anesthesia is not recommended.

PMID- 9152450
TI  - Influence of nitrous oxide on motor-evoked potentials.
AB  - STUDY DESIGN: Rabbits were used as an experimental model in the study of motor
      evoked potentials. OBJECTIVES: To evaluate the effect of nitrous oxide on motor
      evoked potentials while monitoring direct muscle and spinal cord responses.
      SUMMARY OF BACKGROUND DATA: Motor-evoked potential monitoring provides a
      promising tool for intraoperative assessment of descending pathways function.
      However, to date, this technique is still at an experimental stage, since its
      routine use is mainly limited because of intraoperative recording difficulties
      caused by the influence of anesthesia. METHODS: Eight male rabbits weighing
      between 3000 g and 3500 g were studied. Motor-evoked potentials were recorded
      from the extremity muscles and from the epidural space of the thoracic cord in
      response to electrical stimulation of the motor cortex at baseline conditions and
      at increasing nitrous oxide concentrations (10-70 vol%). RESULTS: The authors
      found a major suppressive effect of high nitrous oxide concentrations on the
      electromyographic responses. With 50 vol% nitrous oxide, electromyographic
      amplitudes were suppressed to 46% (fore leg) and 14% (hind leg) of the baseline
      values, whereas latencies did not change significantly. In contrast to muscular
      activity, spinal evoked responses representing neural activity were not affected
      by any concentration of nitrous oxide. CONCLUSIONS: Intraoperative monitoring of
      descending pathways by means of motor-evoked potentials during anesthesia of the
      rabbits based on nitrous oxide is feasible when neural activity is evaluated.
      Higher doses of nitrous oxide, however, are not compatible with recording of
      muscular activity.

PMID- 9152451
TI  - A new method for estimating spinal cord function. Refractory period of conductive
      spinal cord evoked potentials.
AB  - STUDY DESIGN: This study was designed to examine the possibility of a new spinal
      cord monitoring method using measurement of the refractory period to monitor
      spinal cord function. OBJECTIVES: To determine whether measuring the refractory
      period and the recovery rate of conductive spinal cord evoked potential is a
      useful method for estimating spinal cord function. BACKGROUND: Measuring the
      refractory period and constructing the recovery curve have been used to
      investigate peripheral nerve function. Spinal cord evoked potential elicited by
      the single stimulus usually is used to evaluate spinal cord function, and it has
      been said that 50% attenuation of the amplitude is the critical alarm level.
      METHODS: In anesthetized cats, amplitude, area, and latency were measured on a
      personal computer from subtracted data collected with a paired-stimulation
      technique. The authors constructed recovery curves of ascending and descending
      conductive spinal cord evoked potentials and measured the refractory period
      during spinal cord compression. RESULTS: When the amplitude of the ascending
      spinal cord evoked potential began to decrease during spinal cord compression,
      the amplitude of the response elicited by the second stimulus with interstimulus
      intervals of 0.8 msec and 1.0 msec decreased more significantly. When the
      amplitude of the ascending spinal cord evoked potential decreased to 50% of the
      precompression amplitude, the mean value of the absolute refractory periods of
      the ascending and descending spinal cord evoked potentials became prolonged from
      0.40 +/- 0.007 msec to 0.53 +/- 0.014 msec, and the mean values of their
      amplitude and area recovery rates decreased from 75% +/- 1% to 35% +/- 2%
      (interstimulus interval, 0.8 msec) and from 81% +/- 1% to 46% +/- 2%
      (insterstimulus interval, 1.0 msec). CONCLUSIONS: The change of the responses
      elicited by the paired stimuli is more sensitive than those elicited by the
      single stimulus in the spinal cord evoked potentials. The absolute refractory
      periods and the recovery rate during 50% attenuation of the precompression
      amplitude is the critical alarm level in spinal cord monitoring.

PMID- 9152452
TI  - Somatosensory- and motor-evoked potentials in a rabbit model of spinal cord
      ischemia and reperfusion injury.
AB  - STUDY DESIGN: Occlusion of the infrarenal abdominal aorta was applied to adult
      rabbits, which induced spinal cord ischemia, followed by disocclusion and
      reperfusion. Cortical somatosensory- and motor-evoked potentials were monitored
      continuously up to 24 hours and correlated to hind limb motor and sensory status.
      OBJECTIVES: To investigate cortical somatosensory-, and motor-evoked potentials
      in the rabbit model of spinal cord ischemia and reperfusion injury, especially
      their changes during reperfusion and their relationship to hind limb motor and
      sensory function. SUMMARY OF BACKGROUND DATA: Various evoked potentials have been
      widely studied in neurologic prognosis of spinal cord ischemia. Little
      information is available from previous studies to correlate cortical
      somatosensory- and motor-evoked potentials with secondary paraplegia occurring
      during the reperfusion phase. METHODS: Acute spinal cord ischemia was induced in
      eight anesthetized rabbits by occlusion of the infrarenal abdominal aorta just
      beneath left renal artery for 40 minutes. Cortical somatosensory-evoked
      potentials, elicited by stimulating the posterior tibial nerve and recorded at
      the skull surface corresponding to sensory projection area, and motor-evoked
      potentials, elicited by stimulating the skull surface corresponding to the motor
      projection area and recorded at L4 lamina of the vertebral arch, were monitored
      immediately before and at different time points during ischemia and reperfusion
      up to 24 hours after disocclusion. Hind limb motor and sensory functions were
      evaluated and correlated with cortical somatosensory- and evoked-potentials.
      RESULTS: Cortical somatosensory-evoked potentials disappeared gradually after the
      start of occlusion and reappeared during reperfusion. Motor-evoked potentials did
      not change significantly during occlusion, but deteriorated after disocclusion;
      they correlated well with hind limb motor and sensory status. CONCLUSIONS:
      Reperfusion injuries to the spinal cord might occur in the rabbit model after
      disocclusion. Cortical somatosensory-evoked potentials seemed to be a very
      sensitive index for spinal cord ischemia, whereas motor-evoked potentials
      correlated well with the course of reperfusion injuries after disocclusion and
      reflected long-term follow-up hind limb motor function better than cortical
      somatosensory-evoked potentials.

PMID- 9152453
TI  - Changes in serum creatine phosphokinase MM isoenzyme after lumbar spine surgery.
AB  - STUDY DESIGN: Serum concentrations of creatine phosphokinase and its isoenzyme
      were measured serially in 47 patients who underwent lumbar surgery. OBJECTIVE: To
      analyze the significance of postoperative creatine phosphokinase MM levels as
      indicators of muscle trauma after lumbar surgery. SUMMARY OF BACKGROUND DATA: The
      authors of the present study previously have reported on iatrogenic back muscle
      injury in an animal model and in man. However, the relationship between the
      change of the creatine phosphokinase MM isoenzyme level and muscle injury after
      surgery has not been clarified. METHODS: Peripheral venous blood samples were
      collected serially before surgery, just after surgery, and at 1, 3, 7, 14, and 21
      days after surgery. The serum concentration of total creatine phosphokinase and
      its isoenzymes was measured by agarose gel electrophoresis. The serial
      postoperative change of the creatine phosphokinase MM isoenzyme concentration was
      evaluated with respect to age, gender, body weight, types and levels of surgery,
      and surgery time. RESULTS: Creatine phosphokinase MM activity increased after
      surgery and reached a maximum value 1 day after surgery, followed by recovery to
      the normal value 1 week after surgery. The maximum concentration of creatine
      phosphokinase MM isoenzyme in posterior lumbar surgery was significantly higher
      than that in anterior surgery (P = 0.04). It was significantly higher in men than
      in women (P = 0.02). Serum concentration of creatine phosphokinase MM isoenzyme
      showed no significant correlation to the extent of muscle exposure and surgery
      time. CONCLUSION: The time course of postoperative serum creatine phosphokinase
      MM isoenzyme activity is correlated with the histologic changes of the back
      muscles after surgery. The concentration of creatine phosphokinase MM isoenzyme
      in posterior lumbar surgery was significantly higher than that in anterior
      surgery. It was also significantly higher in men than in women.

PMID- 9152454
TI  - Late displacement of a fracture dislocation at the lumbosacral junction. A case
      study.
AB  - STUDY DESIGN: This is a retrospective single-patient case report with a
      literature review. OBJECTIVE: To report on an uncommon injury: traumatic fracture
      dislocation of the lumbosacral junction with delayed displacement. SUMMARY OF
      BACKGROUND DATA: Only 31 cases of traumatic fracture-dislocation of the
      lumbosacral junction were found in the English literature. Only three previous
      reports refer to this injury occurring with a posterior displacement. This is the
      first report of this type of injury displacing in a delayed manner. METHODS:
      Chart review. RESULTS: Open reduction, Arbeitsgemeinschaft fur
      Osteosynthesefargen instrumentation, and interbody fusion resulted in a
      satisfactory clinical result with no neurologic impairment. CONCLUSIONS: The
      present study reports a very rare injury consisting of traumatic dislocation of
      the lumbosacral joint, presenting with displacement 2 months after injury. The
      patient was treated successfully with surgery even though the injury displaced in
      a delayed fashion.

PMID- 9152455
TI  - Intraradicular, intervertebral disc herniation. A case report.
AB  - STUDY DESIGN: A case of intraradicular, intervertebral disc herniation is
      reported. OBJECTIVES: A rupture of en L5-S1 intervertebral disc into the left S1
      nerve root is described. SUMMARY OF BACKGROUND DATA: A review of the literature
      revealed five reported cases with some possible causes of this extremely rare
      phenomenon. METHODS: The diagnosis was made at the time of surgery during
      exploration of the L5-S1 disc space. The S1 nerve root was found to be adherent
      to the underlying disc space. Before surgery, this condition was believed to
      represent a large extradural and extraradicular disc herniation. RESULTS: The
      patient's pain was alleviated almost immediately after surgery, but the patient
      was left with some residual sensory loss in the leg. CONCLUSION: An unusual case
      of intraradicular, intervertebral disc herniation is presented.

PMID- 9152456
TI  - Scoliosis and fused ribs. A case report.
AB  - STUDY DESIGN: This case report illustrates a scoliotic patient with congenital
      fusion of several ribs associated with a thoracic curvature. OBJECTIVES: To
      report the procedure used to correct scoliosis in association with congenitally
      fused ribs. SUMMARY OF BACKGROUND DATA: All cases of congenitally fused ribs
      reported in the literature are associated with malformed vertebrae. For this
      reason, the only proposed treatment for patients with progressive scoliosis is a
      spinal fusion. This report presents the first case of progressive scoliosis
      associated with fused ribs, but without vertebral malformation, that was managed
      by resection of these ribs. METHODS: When worsening of the thoracic scoliosis was
      observed from 30 degrees at 13 months to 44 degrees at 4 years, the three fused
      ribs were resected en bloc. No spinal fusion was performed. The spine was held in
      correction by a localizer cast for 3 months. RESULTS: Fourteen years after
      treatment, the spine is almost normal; thoracic and lumbar curves are 10 degrees.
      CONCLUSIONS: When malformed fused ribs are on the concave side of a progressive
      scoliosis with no vertebral malformation at the same level, resection of these
      ribs is probably an efficient and sufficient method of treatment.

PMID- 9152457
TI  - Traumatic vertical atlantoaxial instability in a case of atlanto-occipital
      coalition.
AB  - STUDY DESIGN: This is a report of a woman with an atlanto-occipital coalition who
      experienced a traumatic vertical atlantoaxial facet dislocation and severe
      associated neurologic injury. OBJECTIVE: To describe the radiographic and
      pathoanatomic characteristics of the injury process. SUMMARY OF BACKGROUND DATA:
      Severe injuries of the occipito-atlantoaxial complex are uncommon and only rarely
      are associated with patient survival. This is the first report of this particular
      injury. METHODS: Plain radiography and tomography demonstrated the facet
      dislocation and instability of the injury. Surgical exploration for repair of the
      torn dura mater and bony arthrodesis demonstrated the gross pathoanatomy.
      RESULTS: The patient's vertical atlantoaxial instability was stabilized, her dura
      mater reconstructed, and her necrologic status has improved to allow mobilization
      with a cane. CONCLUSION: Vertical atlantoaxial instability has not been described
      previously. From the somewhat subtle radiographic findings, one might
      underestimate the severity of the neurologic damage. Aggressive work-up and
      management of this injury is suggested to avoid potential further necrologic
      sequelae.

PMID- 9152459
TI  - Measurements of epidural pressures that occur during walking in patients with or
      without spinal stenosis.

PMID- 9152460
TI  - The struggle against cancer in Italy.

PMID- 9152458
TI  - Primary bone tumors of the spine. Terminology and surgical staging.
AB  - Appropriate application of an oncologic staging system is required to evaluate
      the relationship among histologic types, management, and outcome of primary bone
      tumors. A commonly accepted terminology for surgical procedures and for
      definition of tumor extent is needed for surgical planning and clinical reviews.
      The principles of the Enneking system for classifying stages of tumors are
      emphasized and applied to the spine using a practical approach for surgical
      staging.

PMID- 9152461
TI  - Bridging the gap between clinical oncology and epidemiology.

PMID- 9152462
TI  - Studying survival of cancer patients in different populations: its potential and
      role.
AB  - RATIONALE: Survival figures from a population-based study incorporate the overall
      practice in diagnosis, cure and clinical follow-up for a specific disease within
      a given health care system. Being the outcome of a number of individual, social
      and economical aspects, population-based survival may be thought as index for
      measuring the level of a country's development. DATA: The EUROCARE project, a
      European Cancer Registries (CR) concerted action, provided reliable information
      on survival for more than 800,000 cancer patients from 11 European countries. A
      great deal of epidemiologic information has derived from EUROCARE. Women had a
      longer survival than men for all studied tumour sites, except for the colon.
      European survival variability was fairly high for several cancers, but it was
      lower for cancers with a relatively good prognosis and those sensitive to
      treatment. The ranking of populations of cancer survival tended to be fairly
      stable for many cancers: CR of Switzerland and Finland ranked high and Polish CR
      low. Denmark, Italian and France CR did not substantially differ from the
      European survival average. For most cancers, prognosis improved during the
      studied period (years of diagnosis: 1978-1985). Survival figures for colon (r =
      0.74, males; r = 0.73, women) and female breast cancer (r = 0.57) well correlated
      with the national health expenditure of different participating countries. The
      ITACARE study, a new Italian Cancer Registries collaborative project involving
      more than 100,000 cancer patients, was set up to study survival differences
      within the country. Survival of cancer patients was not homogeneous in 7 studied
      Italian regions (the estimated 5-year relative survival for all malignant
      neoplasms combined ranked from 37.8% in CR of Sicily to 42.1% in those of Emilia
      Romagna). The lowest levels of regional health expenditures were accompanied by
      the lowest levels of prognosis for overall cancers. However, a relatively low
      correlation among patient cancer survival and the regional health expenditure (r
      = 0.21) was found, suggesting that other factors such as different efficiency in
      managing cancer may play a role in explaining the intracountry differences.
      CONCLUSIONS: Population-based survival figures may be used to study epidemiologic
      aspects, comparing different health systems, and may be interpreted as indexes
      for discussing inequalities in health in different populations.

PMID- 9152463
TI  - Interpreting survival differences and trends.
AB  - Since 1990 a concerted action between European population-based cancer registries
      (the EUROCARE project) has been carried out with the aims of establishing whether
      there are differences in cancer patient survival in Europe, and the reasons for
      such differences. Survival differences actually exist for cancer sites for which
      the stage of disease at diagnosis is the major prognostic factor (such as breast,
      stomach and colon cancer). However, for most cancer sites, survival increases
      over time and the survival rates of different countries tend to converge towards
      higher values. Interpreting survival differences and trends is not an easy task.
      Longer survival may be achieved by postponing death through better treatment or
      by anticipating diagnosis. However, an earlier diagnosis may or may not make a
      treatment more effective in postponing death. The computation of stage-specific
      or stage-adjusted survival is not sufficient for interpretation of survival
      differences, because staging procedures change over time and may vary in
      different hospitals and countries. In addition to an early diagnosis and more
      effective treatment, a number of factors may bias survival estimates. They may be
      classified into factors that can be controlled in the analysis (at least
      partially), such as mortality from other causes, demographic factors, epoch of
      diagnosis, different statistical methodology, and factors depending on the
      validity of cancer registry data, such as definition of the illness,
      exhaustiveness and quality of registration, completeness of follow-up, definition
      of the data of diagnosis, and definition of disease stage including the
      diagnostic procedure used to establish stage. To help disentangle the effects of
      early diagnosis and better treatment, several statistical approaches are being
      developed: multivariate analysis on relative survival data, new modeling analysis
      to separately estimate the proportion of cured patients and the length of
      survival for those patients destined to die, and the standardized collection of
      information on stage at diagnosis and staging procedures.

PMID- 9152464
TI  - The ITACARE Study.
AB  - ITACARE is a collaborative study on the survival of Italian cancer patients
      diagnosed in the period 1978-1989. The study involves 11 Italian population-based
      cancer registries (CRs) (Firenze, Forli-Ravenna, Genova, Latina, Modena, Parma,
      Ragusa, Torino, Varese, the childhood CR of Piedmont and the colorectal CR of
      Modena), and its principal aim is to identify and analyze possible differences
      between the areas covered by the CRs. This article describes the ITACARE
      database. Ten percent of the Italian population is covered by the participating
      CRs, most of which are located in the northern part of the country. All malignant
      cancer sites (classified by ICD-9) except skin cancers were included. For bladder
      cancers, papillomas and transitional cell tumours grade 1 and 2 were also
      included. Survival data on over 100,000 cases were collected. The principal
      information variables were sex, date of birth, diagnosis and end of follow-up,
      life status, ICD-9 code for tumour site, diagnosis modality (clinical, cytologic
      confirmation, histologic confirmation), ICD-0 morphology code, and tumour stage
      (grouped into broad categories). Follow-up is active in all registries. All cases
      were checked systematically for errors and inconsistencies, following which about
      0.2% of cases were excluded from the analyses. The percentage of cases
      microscopically verified, which is an indicator of diagnostic accuracy and data
      reliability, was higher among patients under 65 years of age (90%), breast cancer
      patients (92%) and cases covered by the Varese, Torino and Forli-Ravenna CRs
      (more than 82%). The percentage of cases known by death certificate only (an
      indicator of the completeness and quality of registration) was about 3% of total
      cases and was higher among older patients (4%). Province-specific mortality, used
      to compute relative survival from cancer (i.e., survival adjusted for competing
      causes of death), varied according to period of diagnosis, sex and area: the
      highest mortality was among women of the Ragusa CR (Sicily) and men in northern
      CRs. Overall mortality decreased during the period, more markedly in the north
      and among women.

PMID- 9152465
TI  - Comparability issues within the ITACARE data base.
AB  - AIMS AND BACKGROUND: The aim of the study was to describe the extent of
      variability among Italian cancer registries in data managing practices that may
      affect differences in incidence and possibly in survival estimates. METHODS: a
      self-administered questionnaire was sent to each participating registry. The
      definitions of the diseases, of the start point and of the end point of survival
      computation were investigated. Moreover, information on the proportion of
      histologic confirmation, of ill-defined sites and of DCO (death certificate only)
      was also considered. RESULTS: There were some differences in cancer registration
      techniques among Italian cancer registries. As regards disease definition, the
      most relevant problems arose for urinary bladder. Skin melanoma should also be
      considered with some caution, due to variability among registries in coding in
      situ cases. For the CNS and meninges, the proportion of cases that could be
      differently considered was so limited that no effect on survival is expected. For
      female breast, colorectum and cervix uteri, the effect of early diagnosis
      services (which are active only in some areas) may lead to better survival
      estimates. The variability in incidence date definition was high among registries
      and sites, but its effect on survival was very limited. There was a wide
      variability in the proportion of DCOs and of DCIs (initially known from death
      certificate), which should be considered in survival comparisons. All the
      registries stated that they carried out an active follow-up of their patients.
      CONCLUSIONS: In general, quality standards of the registries are good and allow
      comparability of survival data. The variability of rules adopted by Italian
      registries may affect geographic survival differences only in a limited number of
      cancer sites, so that results should be interpreted with caution.

PMID- 9152466
TI  - Estimating relative survival of Italian cancer patients from sparse cancer
      registries data.
AB  - PURPOSE: A method is presented for estimating relative survival of cancer
      patients at the national level from survival data provided by cancer registries
      covering only a subset of the general population and referring to different, and
      not necessarily overlapping, incidence periods. METHODS: Relative survival rates
      are estimated as a function of the covariates sex, age, epoch of diagnosis, and
      registry area by means of a multiple regression model. National estimates are
      then computed by appropriate weighting of the sex-, age-, time- and registry
      specific expected relative survival values. RESULTS: The method is illustrated by
      a sample application to survival data of female breast cancer patients in Italy.
      The national estimates of breast cancer survival pattern show a mild decrease of
      survival with age and a marked increase with period of diagnosis.

PMID- 9152467
TI  - Survival in adult Italian cancer patients, 1978-1989. ITACARE Working Group.
AB  - To present a systematic analysis of population-based cancer patient survival in
      Italy. METHODS: Population-based survival data have been made available from 10
      Italian cancer registries within the ITACARE project. Data, collected and
      validated using a common protocol, included over 100,000 patients with cancer
      diagnosed between 1978 and 1989. Multivariate weighted analysis was used to
      provide relative survival estimates attributable to Italy at national level.
      RESULTS: Results are presented, according to a systematic frame, as the main
      object of the ITACARE study, involving crude and relative survival figures for
      adult Italian cancer patients, by age, sex, period of diagnosis and registry
      area. An estimate with reference to Italy as a whole is also presented by cancer
      site and for all malignant neoplasms combined. Age-standardized relative survival
      figures are presented to allow comparisons between Italian registries and also
      give a basis for international comparisons with countries involved in the
      EUROCARE study. CONCLUSIONS: For the fist time, population-based survival of
      cancer patients is made available in Italy on a large scale analysis of data from
      all the Italian cancer registries in a combined action. Estimates of cancer
      patient survival at a national level in Italy allow proper international
      comparisons with European countries and give elements of evaluation and
      discussion on the performance of the Italian health care system.

PMID- 9152468
TI  - Survival of childhood cancer patients in Italy, 1978-1989. ITACARE Working Group.
AB  - In the framework of the ITACARE project, a cooperative investigation conducted on
      the data from the Italian population-based cancer registries, survival of
      patients with childhood malignant neoplasms was studied. The study included 1,768
      cases diagnosed at age 0-14 plus 29 osteosarcoma cases diagnosed at age 15-19.
      Cases were collected over the period 1978-1989, or more limited periods for some
      participating registries. A total of 1,138 cases were from the Childhood Cancer
      Registry of Piedmont and 659 from the registries operating in the provinces of
      Varese, Parma, Modena, Forli and Ravenna, Florence, Latina, Ragusa and in the
      cities of Genova and Torino (the last contributed only for bone neoplasm
      diagnosed at age 15-19). Overall 5-year survival was 54% for malignancies
      diagnosed in 1978-1981, 60% for the period 1982-1985; and 69% for the period 1986
      1989. The range among registries of 5-year survival for cases diagnosed in 1986
      1989 was 55-78%. Most diagnostic categories presented an improved prognosis for
      the cases diagnosed more recently. For cases diagnosed in 1986-1989, 5-year
      survival was: 74% for acute lymphatic leukaemia, 40% for acute non-lymphatic
      leukaemia, 65% for central nervous system neoplasms (76% for astrocytoma, 75% for
      ependymoma and 85% for medulloblastoma), 66% for osteosarcoma, 55% for Ewing's
      sarcoma, 87% for Hodgkin's disease, 64% for non-Hodgkin's lymphoma, 74% for
      rhabdomyosarcoma, 64% for neuroblastoma, 78% for nephroblastoma and 100% for
      retinoblastoma. Italian survival was similar to that observed in other population
      based surveys in the UK and USA.

PMID- 9152469
TI  - Cancer patient survival in the elderly in Italy. ITACARE Working Group.
AB  - AIMS AND BACKGROUND: Italy, like most western populations, is sharply aging and
      changing its age structure with a striking increase in the oldest segment of the
      elderly. Since age is related to an exponential growth of cancer incidence rates
      and to a worsening of prognosis, the progressive aging of the population will
      constitute, in the future, an issue increasingly more important for public
      health. The present study is the first effort to present and analyze survival
      rates in italian elderly cancer patients in order to provide a starting point for
      the development of better clinical strategies addressed to the aged. MATERIALS
      AND METHODS: The presented data come from a large data set consisting of survival
      data relating to 25,798 men and 20,479 women, aged 65-84 years at diagnosis,
      collected by Italian cancer registries participating in the ITACARE project.
      Relative survival rates of patients have been calculated by sex, quinquennial age
      classes and the considered entire age class for overall malignant neoplasms and
      the 10 most frequent cancer sites in the elderly. RESULTS: When all Italian data
      for all cancers in the 65-84 year age group were pooled, survival rates at 5
      years from the diagnosis was 27% and 39% in men and women, respectively. As
      regards specific sites, survival rates below 50% were observed for lung, stomach
      and ovary cancer at 1 year from diagnosis. At 5 years from diagnosis, the rates
      were less than 50% for colon, prostate, cervix, multiple myeloma, non-Hodgkin's
      lymphoma and melanoma (only in men). The best survival at 5 years from diagnosis
      (above 50%) was in women for melanoma and corpus uteri and breast cancer. For all
      cancers, the prognosis for women was better in each considered age group even
      though a dramatic decrease in survival with age was observed in both sexes. In
      general, a similar decline in survival with increasing age characterized all
      considered specific sites. However, at closer observation, the patterns of a
      decrease revealed some differences. The ratio between the survival rates of 55-64
      vs 65-84 year age class indicated that the sites with the greatest advantage of
      survival for younger patients (ratio > 1.5) were ovary, lung and melanoma (only
      in men), whereas the least advantage was observed for colon, corpus uteri, breast
      and prostate. By calendar periods, excluding non-Hodgkin's lymphoma for women, an
      increase in survival was observed for all considered sites, improving an
      encouraging successful trend in diagnostic and therapeutic progresses.

PMID- 9152470
TI  - Variations in the survival of adult cancer patients in Italy.
AB  - AIMS: As part of the ITACARE project, the present study analyzed and compared
      population-based data on the survival of adult cancer patients in Italy,
      according to sex, age, period of diagnosis and geographical area. METHODS: Nine
      Italian population-based cancer registries provided data on all their cancer
      patients (total 90,431 cases) followed for at least 5 years and diagnosed during
      the period 1978-1989. About 10% of the Italian population is covered by these
      registries. The data was analyzed by means of a multivariate model. RESULTS: The
      major findings were that there was a general improvement in 5-year relative
      survival over the study period (from 33% to 39%) and that there were significant
      differences in survival between different areas of the country, particularly for
      cancer sites which respond well to treatment. In general, the area covered by the
      Ragusa (Sicily) registry was characterized by significantly worse survival than
      other registry populations. Other important findings were that for all malignant
      cancer sites 5-year relative survival decreased with age from 50% for the
      youngest age class (15-44 years) to 27% for the oldest age class (75+ years) and
      that women have a better prognosis for most cancer sites (overall 5-year relative
      survival in women 48% vs 32% in men). CONCLUSIONS: The significant regional
      differences in survival may reflect unequal provision of care, particularly
      between northern-central Italy and the south. The reasons for the general
      survival improvement with time are not completely understood, whereas the marked
      overall sex difference is related to the fact that the commonest cancer in women
      (breast cancer) is eminently more treatable than the commonest malignancy in men
      (lung cancer). The unfavorable trend with increasing age may be due to increasing
      difficulty in applying complete therapy protocols as general health declines,
      sometimes in relation to an advanced cancer stage at diagnosis.

PMID- 9152471
TI  - Inequalities in survival from cancer.

PMID- 9152472
TI  - Sensitivity theory and mental retardation: why functional analysis is not enough.
AB  - Sensitivity theory holds that aberrant behavior is a function of aberrant
      contingencies (direct reinforcement of maladaptive behavior), aberrant motivation
      (a desire for an excessive amount of reinforcement), and aberrant environments
      (situations in which most people cannot satiate their fundamental desires by
      behaving appropriately). Applied behavior analysts are almost exclusively
      concerned with aberrant contingencies and, to a lesser extent, aberrant
      environments. Because they do not treat people for aberrant motivation,
      behaviorists tend to treat the same people repeatedly. When a person craves an
      excessive amount of attention, this desire must be reduced for a durable and
      generalized treatment outcome, but behaviorists do not even try to do this.
      Implications for communication theory, assessment, and treatment strategies were
      discussed.

PMID- 9152473
TI  - Social implications of behavioral interventions for persons with mental
      retardation.
AB  - The influence of type of behavioral program and program outcome on university
      students' perceptions of a hypothetical 17-year-old boy with mental retardation
      who exhibited severe self-injury was examined. A positive program was viewed as
      more acceptable and effective than were other programs (extremely aversive,
      mildly aversive, positive combined with extremely aversive, and control).
      Successful programs were also judged more acceptable and effective than were
      unsuccessful ones. When a program succeeded the individual was also seen as more
      likable, competent, adjusted, capable of learning, responsible, and problem-free.
      These preliminary findings point to the merits of considering the individual's
      social image in evaluating treatment acceptability.

PMID- 9152474
TI  - Developmental change and consistency in parental interactions with school-age
      children who have mental retardation.
AB  - Developmental changes and within-family consistency in parent-child interactions
      were examined for mothers and fathers of school-age children (6 to 18 years) with
      mental retardation. At Time 1 and 18 to 24 months later, 98 families (29 single,
      69 two-parent) with a child who had mild or moderate mental retardation completed
      semi-structured interaction sessions in their homes. As expected, both positive
      and negative exchanges decreased longitudinally, and cross-sectional comparisons
      revealed fewer parent commands, less child noncompliance, fewer child negatives,
      and less parent positive reciprocity with older children. Most behaviors were
      highly consistent between family members and stable over time. Findings were
      discussed in relation to parental responsiveness to developmental changes for the
      child and the coherence of family relationships over time.

PMID- 9152475
TI  - Peer social networks of young boys with developmental delays.
AB  - Community-based peer social networks of young boys with developmental delays and
      parental arranging and monitoring of their child's peer contacts were examined.
      Comparisons were made to matched groups of children who were developing typically
      and to children with communication disorders. Results showed more limited peer
      social networks for both groups of children with disabilities based primarily on
      the frequency of contacts with peers and linkages established across school and
      community settings. All three groups were indistinguishable from one another on
      numerous measures of peer social networks, including duration and quality of
      individual relationships and participation in organized group activities with
      peers. Groups also differed on parental arranging and monitoring, which appeared
      to be related to children's developmental level.

PMID- 9152476
TI  - Residential transitions of adults with mental retardation: predictors of waiting
      list use and placement.
AB  - Predictors of residential planning and placement among 461 families of adults
      with mental retardation living at home were examined prospectively over a 4.5
      year period. Factors predicting whether an adult's name would be put on a waiting
      list for residential placement were a diagnosis of Down syndrome, higher unmet
      service needs, smaller parental support networks, and better maternal health.
      Predictors of residential placement were being on a waiting list, poorer maternal
      health, and older age of the adult child. Result from qualitative analyses of
      parental reasons for use of the waiting list or of placement were also presented.
      Findings were interpreted using stress and coping, family life cycle, and
      postponed launching models.

PMID- 9152478
TI  - Diabetes treatment with implantable delivery devices. Impressed or unimpressed?

PMID- 9152477
TI  - Predicting the earnings of supported employees with mental retardation: a
      longitudinal study.
AB  - A random sample (N = 197) of supported employees with mental retardation was
      examined in a longitudinal study. Results indicate that intelligence, prior
      earnings, and federal job subsidy predicted future earnings. Statistical controls
      applied to the stratified sample show that job placement, job type, subsidy, and
      means of transportation had little influence on earnings.

PMID- 9152479
TI  - The AIMBE President's session: medical device innovation and the public interest.

PMID- 9152480
TI  - International Study Group for Implantable Infusion Devices 1996. The world's only
      implantable infusion pump society.

PMID- 9152481
TI  - Management of diabetes with glucose sensors and implantable insulin pumps. From
      the dream of the 60s to the realities of the 90s.

PMID- 9152482
TI  - ESRD modality selection into the 21st century: the importance of non medical
      factors.

PMID- 9152483
TI  - Molecular biology of nitric oxide synthases. Reduction of complications of
      cardiopulmonary bypass from platelets and neutrophils by nitric oxide generation
      from L-arginine and nitric oxide donors.

PMID- 9152484
TI  - A new biologic membrane in cardiovascular surgery.
AB  - Reconstruction techniques for major vessels and intracardiac defect repair use
      synthetic grafts or autogenic pericardium. Here, autologous abdominal parietal
      peritoneum with the overlying posterior rectus sheath as a biologic membrane are
      evaluated. Twelve adult canines were used. Via a midline subumbilical incision,
      the parietal peritoneum and overlying posterior rectus sheath were harvested. In
      the first group of six, the membrane was used to repair the right ventricular
      infundibulum and perform pulmonary artery annuloplasty. In the second group of
      six, under cardiopulmonary bypass and moderate hypothermia, the right atrium was
      opened and a secundum type defect was created. Autopsies performed 90 days after
      surgery revealed mild intrapericardial adhesions and moderate pericardial
      reaction over the cardiotomy incisions. The right ventricular outflow tract patch
      was nonaneurysmal. The interatrial patch was intact without thrombi. Histologic
      examination revealed intact membrane morphology, fibroblasts, smooth muscle
      cells, and endothelialization. Proline C14 uptake and autoradiography detected
      cellular viability of implanted membranes. These findings suggest that the
      peritoneum with overlying sheath repaired vascular and intracardiac defects and
      substituted for pericardium. Future studies are needed before clinical use.

PMID- 9152485
TI  - Derivation of sieving coefficients to determine the efficacy of the
      hemoconcentrator in removal of four inflammatory mediators produced during
      cardiopulmonary bypass.
AB  - Cardiopulmonary bypass has been implicated in triggering a multisystem
      inflammatory response caused by blood contact with the artificial surfaces of the
      circuit. This leads to increased morbidity levels because of cytotoxic enzymes
      released from activated neutrophils. Recently, it was discovered that certain
      inflammatory mediators are permeable to the membrane of the hemoconcentrator. As
      a result, this study was undertaken to quantitatively characterize the nature of
      this movement by deriving a sieving coefficient (S) for four inflammatory
      mediators: myeloperoxidase, elastase, interleukin-6, and lactoferrin. The results
      show no permeability through the hemoconcentrator for the two neutrophil derived
      enzymes myeloperoxidase and elastase (S = 0, p > 0.05). Conversely, although
      larger than the pore size of the hemoconcentrator, lactoferrin sieves through
      unrestricted (S = 1.030 +/- 0.037, p < 0.0001). Interleukin-6 is removed in
      concentrations greater than those found in the blood, which yields a sieving
      coefficient significantly greater than 1.0 (S = 1.246 +/- 0.042, p < 0.0001). In
      addition to sieving coefficients, this study offers theories as to why these
      mediators acted as such. One conclusion is that certain mediators are
      efficaciously removed by the hemoconcentrator and, with additional study, may
      result in an attenuated inflammatory response.

PMID- 9152486
TI  - Venoarterial shunting for the treatment of right sided circulatory failure after
      left ventricular assist device placement.
AB  - Right sided circulatory failure (RSCF), a common complication after left
      ventricular assist device (LVAD) implantation, results in decreased systemic
      output due to diminished blood flow across the pulmonary vasculature. The authors
      hypothesized that creation of a venoarterial shunt (VAS) would decompress the
      right-sided circulation and improve systemic pressure and perfusion with
      significant arterial desaturation. An experimental model was created in which
      RSCF was induced acutely in a large animal (n = 6) by beta-blockade after LVAD
      placement. After VAS creation, hemodynamic and blood gas determinations were
      performed to compare non shunt and shunt states. After induction of heart failure
      after LVAD placement, VAS resulted in a 22% elevation in systemic blood pressure
      (p < 0.0001), a 36% elevation in cerebral blood flow (p = 0.02), and an 18%
      decrease in right sided filling pressures (p = 0.08). Systemic pH and aortic
      oxygen saturation remained unchanged from baseline. In a large animal model of
      RSCF after LVAD implantation, VAS improves systemic hemodynamics without a
      significant cost in arterial oxygenation to critical organs and without creating
      acid-base imbalance. Beside implementation, adjustable capabilities, easy removal
      and salutatory hemodynamic effects suggest that VAS may serve as a first line,
      short-term therapy for LVAD recipients who develop perioperative RSCF.

PMID- 9152487
TI  - Asymptomatic microembolism in patients with long-term ventricular assist support.
AB  - The incidence of clinically significant thromboembolic events is reported to be
      as high as 25% in patients with left ventricular assist devices (LVAD).
      Clinically detectable neurologic deficits resulting from thromboembolic events
      are reported to occur at a frequency of 0.0056% per patient-month with the Thermo
      Cardiosystems Heartmate 1000 (Woburn, MA) intraperitoneal LVAD (TCI). To date,
      the occurrence of asymptomatic cerebral microemboli in patients with this device
      has not been characterized. Transcranial doppler (TCD) monitorings were used for
      evaluation of the incidence of cerebral microembolism in 14 patients with the TCI
      LVAD. Studies were performed after LVAD support ranging from 7 to 305 days.
      Overall, 35 studies were obtained from the left middle cerebral artery for a
      duration of 30 minutes per study and the number of high intensity transient
      signals (HITS) were recorded. In one patient with a fatal stroke, an average of
      0.86 HITS per study period (0.03/min) was observed. In 13 patients without any
      symptoms, an average of 0.46 HITS per study (0.016/min) was observed. Overall, no
      HITS were determined in 74% of the studies. Although the clinical significance or
      the nature of these microemboli is unknown, the data support that microembolism
      with the TCI LVAD is a rare event despite absence of anticoagulation. Long-term
      detailed neurocognitive testing and hematologic assessment is needed to establish
      the clinical relevance of these microemboli in patients with detected signals.

PMID- 9152488
TI  - Collagen synthesis is upregulated in mitral valves subjected to altered stress.
AB  - Mitral regurgitation (MR) and abnormal ventricular wall motion (AVWM) are two
      cardiac conditions that may increase mitral valve (MV) stresses. Theoretically,
      increased stress could induce damaging MV tissue alterations. These alterations
      may impair the preferred option of repair, and mandate replacement. It is
      hypothesized that MV collagen synthesis is upregulated in response to MR and
      AVWM. To test this hypothesis in a pilot study, an ischemic sheep model (n = 8)
      was employed. Four sheep underwent selective coronary artery ligation to infarct
      a papillary muscle, which resulted in MR. Two other sheep underwent similar
      coronary ligation to create AVWM. As controls, two sheep underwent sham surgery
      (no ligation). Sheep were killed 4 and 8 weeks post operatively and their MVs
      were sectioned. Sections were stained with an antibody (SP1.D8, University of
      Iowa) to procollagen I (precursor to collagen I). The percent area of procollagen
      stain present present was measured by image analysis (Optimas Corporation) and
      used as an indicator of collagen synthesis. Procollagen results indicated that MV
      collagen synthesis was upregulated by factor of 1.8 in both the MR and AVWM
      groups versus controls. In addition, results showed greater upregulation in
      anterior leaflets compared with posterior leaflets in both infarct groups. These
      results indicate that MV collagen synthesis is upregulated in response to MR and
      AVWM.

PMID- 9152489
TI  - Experimental study of combination of extraaortic balloon counterpulsation and
      ventricular assist cup to acute heart failure in dogs.
AB  - The goal of this study is to evaluate the applicability and effectiveness of
      combination support of the extraaortic balloon (EAB) and the ventricular assist
      cup (VAC) to the acute heart failure model. Under general anesthesia, 10 adult
      dogs were used. Through the median sternotomy, EAB was placed around the
      ascending aorta and VAC in the pericardial cavity. After heart failure was
      induced by administration of propranolol, the on-off tests of devices were done
      as follows. Only EAB was used, and only VAC was used and both devices were used.
      Regional blood flows (RBFs) of both ventricles, liver kidneys, and brain were
      measured by colored microsphere technique. Hemodynamic parameters were also
      measured. In heart failure model, cardiac output (CO) decreased to 66% of control
      value. In the group assisted by EAB, aortic peak-diastolic pressure and RBFs of
      both ventricle and brain increased significantly. In the group assisted by VAC,
      CO and RBFs of all but the left ventricle significantly increased. In the group
      assisted by EAB and VAC, aortic peak-diastolic pressure, CO, and all five RBFs
      significantly increased. These results suggest the combination of EAB and VAC is
      applicable and effective and would be a promising implantable device for the
      chronic heart failure.

PMID- 9152490
TI  - Albumin priming does not prolong hemofilter life.
AB  - The hypothesis was tested that prepriming a hemofilter and lines with heparinized
      human albumin (NSA) instead of heparinized saline (NS) increases filter survival
      time. In a university affiliated intensive care unit, all patients were eligible
      who required continuous venovenous hemodiafiltration and who did not have pre
      existing coagulopathy or contraindications to heparin. New hemofilters were
      randomized to priming with 2 liters NS or 1 liter NS followed by 500ml NSA. The
      prime was recirculated for at least 30 minutes before connection to the patient.
      Anticoagulation was tightly controlled, aiming for a patient activated partial
      thromboplastin time (APTT) of 60 seconds. Survival analysis was used to compare
      filter life. Elective discontinuation (e.g., for surgery) were treated as
      censored data. A total of 91 hemofilters were used in 40 patients during 9
      months: 45 randomized to NS, and 46 to NSA. Of these, 57 hemofilters were used
      until spontaneous failure, 28 NS and 29 NSA; 34 hemofilters were electively
      discontinued, 17 in each group. Anticoagulation was identical in both groups; the
      mean APTT value (+/- SE) was 58.2 seconds (+/- 3.1) for NS and 58.0 seconds (+/-
      2.8) for NSA (p > 0.9 unpaired t-test). Platelet counts were very similar at 170
      x 10(9) (+/- 21.8) for NS and 181 x 10(9) (+/- 23.7) for NSA (p = 0.74 unpaired t
      test). There was no significant difference in the filter life between the two
      groups. For NS, median filter life was 37.8 hours (range 0.6-120); for NSA,
      median filter life was 45.4 hours (range 2.5-109; p = 0.998 log rank). The power
      to detect a 50% improvement in filter life was > 90%. Based on this data, the use
      of albumin priming as an aid to increased hemofilter life can not be recommended.

PMID- 9152491
TI  - A new intraurethral sphincter prosthesis with a self contained urinary pump.
AB  - An intraurethral sphincter prosthesis with a self contained urinary pump for the
      management of atonic bladder in women was developed and tested. The prosthesis is
      comprised of a short, self retaining silicone catheter in which there is a valve
      and pump. Available in a range of lengths and diameters according to urethral
      size, its insertion is similar to that of a urethral catheter. The prosthesis is
      secured by a novel fixation method that has soft expandable silicone fins at the
      bladder neck and a flexible flange at the external meatus. It is activated by a
      small hand-held control device. To urinate, the activator is placed on the lower
      abdomen area and the "on" button is pressed, providing energy to the pump by a
      magnetic coupling method. Once activated, the valve opens and the pump rotates at
      a high speed, drawing urine from the bladder and pushing it forward, allowing the
      patient to "void" with a urine flow of 10 to 12 cc/sec. When the bladder is
      completely evacuated, the pumping ceases and the valve closes, restoring
      continence. The device was evaluated clinically in 17 women. Fifteen of the
      patients had a range of use of 2 weeks to 16 months during which they were dry
      and had complete bladder emptying. Two patients did not tolerate the device
      because of uninhibited detrusor contractions and, in both cases, it was removed
      without complication after 5 days.

PMID- 9152492
TI  - Bladder neck suspension using bone anchors for the treatment of female stress
      incontinence.
AB  - A new technique and related devices for the treatment of urinary incontinence in
      women was developed and tested. The technique involves soft tissue to bone
      fixation by means of miniature bone anchors and a bone anchor inserter. The novel
      bone anchors are made of a shape-memory nickel titanium alloy (Nitinol) attached
      to Polypropylene or Gortex suture. A spring-loaded bone anchor inserter drives
      the anchors through the vaginal wall to a predetermined depth into the pubic bone
      medulla regardless of the bone's hardness, with no incision or drilling required.
      The device allows for the performance of a minimally invasive transvaginal
      bladder neck suspension. The procedure has minimal morbidity and a short learning
      curve. This technique was evaluated clinically in 15 women with incontinence,
      with a mean follow-up of 6 months. Good urinary continence was achieved in all
      patients, with no mechanical failures.

PMID- 9152494
TI  - A small portable proton exchange membrane fuel cell and hydrogen generator for
      medical applications.
AB  - Small, lightweight power sources for total artificial hearts (TAH), left
      ventricular assist devices (LVAD), and other medical products are under
      development. The new power source will provide 2 to 3 times the capacity of
      conventional batteries. The implications of this new power source are profound.
      For example, for the Heartmate LVAD, 5 to 8 hours of operation are obtained with
      3 lb of lead acid batteries (Personal Communication Mr. Craig Sherman, Thermo
      Cardiosystems, Inc TCI 11/29/96). With the same weight, as much as 14 hours of
      operation appear achievable with the proton exchange membrane (PEM) fuel cell
      power source. Energy densities near 135 watt-hour/L are achievable. These values
      significantly exceed those of most conventional and advanced primary and
      secondary batteries. The improvement is mission dependent and even applies for
      the short deployment cited above. The comparison to batteries becomes even more
      favorable if the mission length is increased. The higher capacity requires only
      replacement of lightweight hydride cartridges and logistically available water.
      Therefore, when one spare 50 L hydride cartridge weighing 115 g is added to the
      reactant supply the energy density of the total system increases to 230 watt
      hour/kg. This new power source is comprised of a hydrogen fueled, air-breathing
      PEM fuel cell and a miniature hydrogen generator (US Patent No 5,514,353). The
      fuel cell is of novel construction and differs from conventional bipolar PEM fuel
      cells by the arrangement of cells on a single sheet of ion-exchange membrane. The
      construction avoids the weight and volume penalty of conventional bipolar stacks.
      The hydrogen consumed by the fuel cell is generated load-responsively in the
      miniature hydrogen generator, by reacting calcium hydride with water, forming in
      the process hydrogen and lime. The generator is cartridge rechargeable and
      available in capacities providing up to several hundred watt-hours of electric
      power.

PMID- 9152493
TI  - Low density lipoprotein-apheresis decreases oxidized low density lipoproteins and
      monocyte adhesion to endothelial cells.
AB  - The mutual interaction between monocytes and low density lipoprotein (LDL) in
      atherogenesis prompted a test of the hypothesis that LDL-apheresis could reduce
      the adhesive properties of monocytes to endothelium; and therefore interfere with
      a key mechanism in atheroma formation. Five patients affected by heterozygous
      familial hypercholesterolemia were studied. All patients received LDL-apheresis
      treatment with selective adsorption of LDL-cholesterol on dextran-sulphate
      columns. Low density lipoprotein particles were isolated by sequential
      preparative ultracentrifugation and subfractionated by ion exchange high
      performance liquid chromatography. Thiobarbituric acid reacting products of lipid
      peroxidation were measured fluorometrically. Vitamin E was estimated by high
      performance liquid chromatographic technique. Monocytes were isolated from
      patients blood before and 1 day after LDL-apheresis by Percoll gradient. The
      blood samples for monocyte adhesion were drawn from control subjects for 2
      consecutive days. The adhesion of monocytes to an endothelial monolayer was
      evaluated by assaying the peroxidase content of the adherent monocytes. Low
      density lipoprotein-apheresis reduced total cholesterol (-65%; p < 0.01), LDL
      cholesterol (-75%; p < 0.01), triglycerides (-51%; p < 0.05), and fibrinogen (
      28%; p < 0.01). With LDL-apheresis treatment, a reduction of 54% in oxidized LDLs
      was observed; vitamin E concentration significantly increased in LDLs (+ 14.2%; p
      < 0.05). The monocyte adhesion decreased by approximately 61% after apheresis;
      the variation became statistically significant (-65%; p < 0.01) when endothelial
      cells were stimulated by lipopolysaccaride.

PMID- 9152495
TI  - Duration and adequacy of dialysis. Overview: the science is easy, the ethic is
      difficult.
AB  - Because of physiologic, technical, and practical limits, short dialysis is
      probably associated with higher mortality when compared with longer dialysis,
      even when dialysis efficiency is maintained with a proportionately higher
      clearance. The optimal dialysis efficiency measured as KT/V (or better expressed
      as mean standardized urea clearance in ml/min) for hemodialysis, remains unknown,
      but it is not unreasonable to assume that either a KT/V of 3 or a mean
      standardized urea clearance of 30 ml/min is optimal, and certainly better than
      the presently used KT/V of 1.2 to 1.8. To achieve KT/Vs on this order, a 70 kg
      patient will need at least 7 hours of dialysis 3 times per week. This gives rise
      to an ethical problem: Should one give many patients short dialysis, or fewer
      patients longer dialysis? This is a question to which no easy ethical solution
      can be found.

PMID- 9152496
TI  - Treatment time for hemodialysis. What should it be?

PMID- 9152497
TI  - Dialysis time. What should it be?

PMID- 9152498
TI  - Cost effectiveness of artificial organ technologies versus conventional therapy.

PMID- 9152499
TI  - Fluid mechanical considerations in vascular grafts. Overview.

PMID- 9152500
TI  - Failure modes and performance of synthetic, autologous, and endovascular grafts.

PMID- 9152501
TI  - In vitro studies on anastomotic intimal hyperplasia.

PMID- 9152502
TI  - Nutritional monitoring techniques in dialysis. Can routine monitoring impact
      outcome?

PMID- 9152503
TI  - Nutritional status as a predictor of morbidity and mortality in maintenance
      dialysis patients.
AB  - Many epidemiologic studies indicate that protein-energy malnutrition is a strong
      predictor of morbidity and mortality in maintenance hemodialysis and chronic
      peritoneal dialysis patients. Those parameters of protein-energy malnutrition
      that have been most clearly associated with morbidity or mortality include serum
      albumin, dietary protein intake as indicated by the protein equivalent of total
      nitrogen appearance (PNA, also referred to as PCR), and the predialysis serum
      urea nitrogen. In large scale clinical surveys, low predialysis serum creatinine,
      cholesterol, potassium, phosphorus, calcium, and bicarbonate also correlate with
      increased mortality rates in maintenance hemodialysis patients. These
      correlations may reflect an association between dietary intake and mortality. The
      paucity of data correlating energy intake or body composition (e.g., total body
      protein or nitrogen, skeletal muscle mass, total body fat) with clinical outcome
      may reflect the difficulty of obtaining these data in large scale prospective or
      retrospective analyses. The correlation between protein-energy malnutrition and
      increased morbidity and mortality rates does not prove that a higher protein
      and/or energy intake or a more optimal body composition will improve the
      patient's outcome. Prospective, randomized studies will be necessary to examine
      this question. However, two retrospective analyses of the effect of intradialytic
      parenteral nutrition on mortality rates in maintenance hemodialysis patients are
      consistent with the thesis that increased nutrient intake will reduce mortality
      in maintenance hemodialysis patients. Methods for assessing protein-energy
      nutritional status are discussed. There are essentially no data indicating that
      the more complicated and expensive techniques for nutritional assessment have
      important advantages over the more simple methods for the clinical management of
      maintenance dialysis patients.

PMID- 9152504
TI  - Validation of body composition assessment techniques in the dialysis population.
AB  - Assessment of body composition remains a goal for the routine assessment of
      nutritional status of patients on long-term dialysis. Methods generally available
      for estimation of body fat in healthy individuals are limited by practicality and
      availability for use in this patient population. Anthropometry, which is cost
      effective and easy to perform, is limited by the lack of appropriate reference
      standards for patients on dialysis and artifact caused by hydration status.
      Bioelectrical impedance affords new opportunities for non-invasive assessment of
      fluid volume, its distribution, and body cell mass; estimation of fat-free mass
      and body fat can be affected by hydration status. Dual x-ray absorptiometry
      permits estimation of bone status and fat mass because changes in hydration
      status are reflected in estimates of fat-free mass. Evaluation of validity of
      techniques for fluid status and body composition assessment requires the use of
      appropriate reference methods and proper statistical procedures to examine error,
      not only between groups, but by individual. Use of body composition assessment
      methods together with biochemical measurements will enhance the nutritional
      assessment of end-stage renal disease patients on long-term hemodialysis.

PMID- 9152506
TI  - Biomaterials availability: the public policy challenge.

PMID- 9152505
TI  - Use of bioelectric impedance analysis and dual-energy X-ray absorptiometry for
      monitoring the nutritional status of dialysis patients.
AB  - Despite recent technological advances, inadequate nutrition has been clearly
      identified as a significant risk factor to survival of patients undergoing
      chronic maintenance dialysis therapy. Although body density by underwater weight
      and residual lung volume, total body water by isotope dilution, bone mineral
      content, and total body potassium measurements will provide a very accurate
      multicompartmental analysis of body composition, they are not applicable to
      routine clinical or field work. Because of availability and simplicity, in
      addition to anthropometry, bioelectrical impedance and dual energy X-ray
      absorptiometry have received the most attention from the renal community. Several
      studies have validated the use of total body water by BEI as a surrogate for
      isotope dilution methods in dialysis patients, whereas others have established an
      excellent correlation with the volume of distribution of urea as measured by urea
      kinetic volume. Bioimpedance analysis has been extensively validated in stable
      healthy populations for measurement of lean body mass. Results are similar to
      those obtained with hydrodensitometry and total body potassium. Several studies
      in dialysis patients have compared lean body mass measurements by BEI and DEXA.
      Although the number of patients studied is relatively small, there is a high
      degree of correlation and concordance between the two methods. Nevertheless,
      selective equations for specific patient populations may be required with both
      methodologies for individual clinical applications. Longitudinal follow-up of
      body composition using BEI and DEXA in dialysis patients is contingent on a
      stable hydration status and/or accurate estimation of extracellular volume status
      for appropriate corrections. Consistency of technique and standardization of BEI
      and DEXA equipment is essential for reproducibility of results. Equations used in
      calculations must be age, sex, race, body habitus, and population specific
      whenever possible. Multiple compartment models including BEI, DEXA and isotopic
      dilution provide the best current "gold standard" for body composition analysis.
      BEI methodology is a practical bedside tool for assessment of total body water,
      and provides more consistent and reproducible results than anthropometry.

PMID- 9152507
TI  - Selenium and other antioxidants in viral diseases. Introduction.

PMID- 9152508
TI  - Interacting nutritional and infectious etiologies of Keshan disease. Insights
      from coxsackie virus B-induced myocarditis in mice deficient in selenium or
      vitamin E.
AB  - In 1979, Chinese scientists reported that selenium had been linked to Keshan
      disease, an endemic juvenile cardiomyopathy found in China. However, certain
      epidemiological features of the disease could not be explained solely on the
      basis of inadequate selenium nutrition. Fluctuations in the seasonal incidence of
      the disease suggested involvement of an infectious agent. Indeed, a
      coxsackievirus B4 isolated from a Keshan disease victim caused more heart muscle
      damage when inoculated into selenium-deficient mice than when given to selenium
      adequate mice. Those results led us to study the relationship of nutritional
      status to viral virulence. Coxsackievirus B3/0 (CVB3/0), did not cause disease
      when inoculated into mice fed adequate levels of Se and vitamin E. However, mice
      fed diets deficient in either Se or vitamin E developed heart lesions when
      infected with CVB3/0. To determine if the change in viral phenotype was
      maintained, we passaged virus isolated from Se-deficient hosts, designated as
      CVB3/0 Se-, back into Se-adequate hosts. The CVB3/0 Se- virus caused disease in
      Se-adequate mice. To determine if the phenotype change was due to changes in the
      viral genome, we sequenced viruses isolated from Se-deficient mice and compared
      them with the input CVB3/0 virus. Six point mutations differed between the parent
      strain and the recovered CVB3/0 Se- isolates. When the experiment was repeated
      using vitamin E-deficient mice, the same 6 point mutations were found. This is
      the first report of a specific host nutritional deficiency altering viral
      genotype. Keshan disease may be the result of several interacting causes
      including a dominant nutritional deficiency (selenium), other nutritional factors
      (vitamin E, polyunsaturated fatty acids), and an infectious agent (virus).

PMID- 9152509
TI  - RNA virus evolution, population dynamics, and nutritional status.
AB  - Trace elements exert a strong influence on immune function. Debilitated humoral
      and cellular immune responses may impair virus clearance in infected organisms,
      and favor the generation of virus variants with altered biological properties.
      The population size in evolving viral quasispecies, as well as increased
      mutagenesis triggered by oxidative stress, may contribute to altering the outcome
      of quasispecies evolution in infected hosts. The genetic plasticity of RNA
      viruses is one of the main obstacles for the control of the diseases they cause
      and probably a major force in the emergence of new viral pathogens. Recent
      results suggest links between nutritional deficiencies and the generation of
      variant viruses, a possibility that is addressed in the present article.

PMID- 9152510
TI  - Serum selenium versus lymphocyte subsets and markers of disease progression and
      inflammatory response in human immunodeficiency virus-1 infection.
AB  - Serum selenium levels were determined cross-sectionally in 57 HIV-infected
      patients who were classified according to the Centers for Disease Control (CDC)
      1993 classification system. Mean serum selenium levels were lower in CDC stage II
      (58.7 +/- 12.2 micrograms/L; p < 0.01; n = 18) and stage III (47.6 +/- 11.3
      micrograms/L; p < 0.01; n = 19) HIV-infected patients, than in healthy subjects
      (80.6 +/- 9.6 micrograms/L; n = 48) and stage I patients (73.6 +/- 16.5
      micrograms/L; n = 20). Serum selenium levels were positively correlated with CD4
      count, CD4/8 ratio, hematocrit, and serum albumin (r = 0.42; r = 0.39; r = 0.48;
      and r = 0.45; p < 0.01, respectively) and inversely with serum levels of
      thymidine kinase (r = -0.49; p < 0.01; n = 49) and beta 2-microglobulin (r = 
      0.46; p < 0.001; n = 49). In addition, serum selenium levels in 20 randomly
      selected AIDS-free individuals (CDC I: n = 10; CDC II: n = 10) were inversely
      correlated with serum concentrations of interleukin-8 (IL-8) and soluble tumor
      necrosis factor receptors (sTNFR) types I and II. There was no correlation with
      serum immuneglobulin A and total serum protein levels. The results show that the
      progressive deprivation of serum selenium in HIV-infection is associated with
      loss of CD(4+)-cells and with increased levels of markers of disease progression
      and inflammatory response.

PMID- 9152511
TI  - The distribution of selenium and mortality owing to acquired immune deficiency
      syndrome in the continental United States.
AB  - A hypothesis has been proposed that Selenium (Se) concentration in the
      environment as measured by its uptake by alfalfa, which sorbs Se from the soil in
      proportion to what is present, exerted an apparent effect on incidence of
      (acquired immune deficiency syndrome) AIDS such that AIDS' mortality within the
      conterminous United States was lower where the Se quantity in the soil was high
      than where the amount was low. The object of this study was to test this
      hypothesis for statistical significance and to discover whether the apparent
      pattern of AIDS mortality in relation to Se distribution holds true with respect
      to all ages, both races (Black and White), and both genders. The statistical
      analysis employed was analysis of variance. Age-specific data as well as age
      adjusted data were subject to statistical analysis. Ages where AIDS mortality
      rates per 100,000 were greatest were in the range from 25-54 yr for low-, medium
      , and high-Se areas of the US. Black mortality owing to AIDS showed highly
      statistically significant results for the three Se regions, both genders, and six
      age groups, whereas White mortality was not as significantly affected by Se. A
      hypothesis is proposed that the Black population during the last decade or so has
      been less migratory than the White population. Thus, their food supply and hence
      its Se content have been more stable than that of the White population, which is
      more prone to consume imported foods to unknown Se content and be more migratory.
      A second hypothesis is advanced that suggests that medical care is not equally
      available to the poor and especially poor Blacks. Black men and women die at a
      greater death rate than do Whites. This implies that a lack of medical care is
      the true cause. This article suggests that a pattern exists between the
      geographical distribution of Se using alfalfa as a dietary guide and AIDS'
      mortality such that an inverse relationship persists between Se quantity in an
      area and AIDS' mortality in the same area.

PMID- 9152512
TI  - Genomic structures of viral agents in relation to the biosynthesis of
      selenoproteins.
AB  - The genomes of both bacteria and eukaryotic organisms are known to encode
      selenoproteins, using the UGA codon for seleno-cysteine (SeC), and a complex
      cotranslational mechanism for SeC incorporation into polypeptide chains,
      involving RNA stem-loop structures. These common features and similar codon usage
      strongly suggest that this is an ancient evolutionary development. However, the
      possibility that some viruses might also encode selenoproteins remained
      unexplored until recently. Based on an analysis of the genomic structure of the
      human immunodeficiency virus HIV-1, we demonstrated that several regions
      overlapping known HIV genes have the potential to encode selenoproteins (Taylor
      et al. [31], J. Med. Chem. 37, 2637-2654 [1994]). This is provocative in the
      light of overwhelming evidence of a role for oxidative stress in AIDS
      pathogenesis, and the fact that a number of viral diseases have been linked to
      selenium (Se) deficiency, either in humans or by in vitro and animal studies.
      These include HIV-AIDS, hepatitis B linked to liver disease and cancer, Coxsackie
      virus B3, Keshan disease, and the mouse mammary tumor virus (MMTV), against which
      Se is a potent chemoprotective agent. There are also established biochemical
      mechanisms whereby extreme Se deficiency can induce a proclotting or hemorrhagic
      effect, suggesting that hemorrhagic fever viruses should also be examined for
      potential virally encoded selenoproteins. In addition to the RNA stem-loop
      structures required for SeC insertion at UGA codons, genomic structural features
      that may be required for selenoprotein synthesis can also include ribosomal
      frameshift sites and RNA pseudoknots if the potential selenoprotein module
      overlaps with another gene, which may prove to be the rule rather than the
      exception in viruses. One such pseudoknot that we predicted in HIV-1 has now been
      verified experimentally; a similar structure can be demonstrated in precisely the
      same location in the reverse transcriptase coding region of hepatitis B virus.
      Significant new findings reported here include the existence of highly
      distinctive glutathione peroxidase (GSH-Px)-related sequences in Coxsackie B
      viruses, new theoretical data related to a previously proposed potential
      selenoprotein gene overlapping the HIV protease coding region, and further
      evidence in support of a novel frameshift site in the HIV nef gene associated
      with a well-conserved UGA codon in the 1-reading frame.

PMID- 9152513
TI  - Computational genomic analysis of hemorrhagic fever viruses. Viral selenoproteins
      as a potential factor in pathogenesis.
AB  - A number of distinct viruses are known as hemorrhagic fever viruses based on a
      shared ability to induce hemorrhage by poorly understood mechanisms, typically
      involving the formation of blood clots ("disseminated intravascular
      coagulation"). It is well documented that selenium plays a significant role in
      the regulation of blood clotting via its effects on the thromboxane/prostacyclin
      ratio, and effects on the complement system. Selenium has an anticlotting effect,
      whereas selenium deficiency has a proclotting or thrombotic effect. It is also
      well documented that extreme dietary selenium deficiency, which is almost never
      seen in humans, has been associated with hemorrhagic effects in animals. Thus,
      the possibility that viral selenoprotein synthesis might contribute to
      hemorrhagic symptoms merits further consideration. Computational genomic analysis
      of certain hemorrhagic fever viruses reveals the presence of potential protein
      coding regions (PPCRs) containing large numbers of in-frame UGA codons,
      particularly in the -1 reading frame. In some cases, these clusterings of UGA
      codons are very unlikely to have arisen by chance, suggesting that these UGAs may
      have some function other than being a stop codon, such as encoding
      selenocysteine. For this to be possible, a downstream selenocysteine insertion
      element (SECIS) is required. Ebola Zaire, the most notorious hemorrhagic fever
      virus, has a PCR with 17 UGA codons, and several potential SECIS elements can be
      identified in the viral genome. One potential viral selenoprotein may contain up
      to 16 selenium atoms per molecule. Biosynthesis of this protein could impose an
      unprecedented selenium demand on the host, potentially, leading to severe lipid
      peroxidation and cell membrane destruction, and contributing to hemorrhagic
      symptoms. Alternatively, even in the absence of programmed selenoprotein
      synthesis, it is possible that random slippage errors would lead to increased
      encounters with UGA codons in overlapping reading frames, and thus potentially to
      nonspecific depletion of SeC in the host.

PMID- 9152515
TI  - Protective role of selenium against hepatitis B virus and primary liver cancer in
      Qidong.
AB  - High rates of hepatitis B virus (HBV) infection and primary liver cancer (PLC)
      are present in Qidong county. Epidemiological surveys demonstrated an inverse
      association between selenium (Se) level and regional cancer incidence, as well as
      HBV infection. Four-year animal studies showed that dietary supplement of Se
      reduced the HBV infection by 77.2% and liver precancerous lesion by 75.8% of
      ducks, caused by exposure to natural environmental etiologic factors. An
      intervention trial was undertaken among the general population of 130,471.
      Individuals in five townships were involved for observation of the preventive
      effect of Se. The 8-yr follow-up data showed reduced PLC incidence by 35.1% in
      selenized table salt supplemented vs the nonsupplemented population. On
      withdrawal of Se from the treated group, PLC incidence rate began to increase.
      However, the inhibitory response to HBV was sustained during the 3-yr cessation
      of treatment. The clinical study among 226 Hepatitis B Surface Antigen (HBsAg)
      positive persons provided either 200 micrograms of Se in the form of selenized
      yeast tablet or an identical placebo of yeast tablet daily for 4 yr showed that 7
      of 113 subjects were diagnosed as having PLC in the placebo group, whereas no
      incidence of PLC was found in 113 subjects supplemented with Se. Again on
      cessation of treatment, PLC developed at a rate comparable to that in the control
      group, demonstrating that a continuous intake of Se is essential to sustain the
      chemopreventive effect.

PMID- 9152514
TI  - Reactive oxygen species and nitric oxide in viral diseases.
AB  - Metabolites derived from superoxide (O2.-) and nitric oxide (NO.) play an
      important role in antimicrobial and antitumoral defense, but may also harm the
      host. Low levels of such metabolites can also facilitate viral replication
      because of their mitogenic effects on cells. Most viruses grow better in
      proliferating cells, and indeed, many viruses induce in their host cell changes
      similar to those seen early after treatment with mitogenic lectins. Influenza and
      paramyxo-viruses activate in phagocytes in the generation of superoxide by a
      mechanism involving the interaction between the viral surface glycoproteins and
      the phagocyte's plasma membrane. Interestingly, viruses that activate this host
      defense mechanism are toxic when injected in the bloodstream of animals. Mice
      infected with influenza virus undergo oxidative stress. In addition, a wide array
      of cytokines are formed in the lung, contributing to the systemic effects of
      influenza. Oxidative stress is seen also in chronic viral infections, such as
      AIDS and viral hepatitis. Oxidant production in viral hepatitis may contribute to
      the emergence of hepatocellular carcinoma, a tumor seen in patients after years
      of chronic inflammation of the liver. Antioxidants and agents that downregulate
      proinflammatory cytokines and lipid mediators may be a useful complement to
      specific antiviral drugs in the therapy of viral diseases.

PMID- 9152517
TI  - Possibilities of a viral etiology for human breast cancer. A review.
AB  - Previous studies related mouse mammary tumor virus (MMTV) to human breast cancer.
      However, the presence of human endogenous retroviruses (HERs) confounded these
      results. We selected a 660-bp sequence of the MMTV env gene with low homology to
      HER (or any other known gene) and searched for a sequence homologous to it, using
      the polymerase chain reaction (PCR). The 660-bp sequence was detected in 131
      (39%) of 335 unselected breast cancers, in 2 (6.9%) of 29 fibroadenomas, and in 2
      (1.65%) of 121 normal breast specimens. The sequence was not present in normal
      tissues, or in other human cancers or cell lines. Cloning and sequencing of the
      660-bp sequence revealed that it is 95-98% homologous to MMTV env gene, but not
      the known HERs or other viral or human gene. Southern blot hybridization using
      labeled cloned sequences demonstrated that the 660-bp sequence was present in
      very low copy number as a 6-8 kb EcoRI fragment only in breast cancer samples and
      in some of the human breast cancer cell lines that were positive by PCR.
      Preliminary experiments using reverse transcriptase (RT)-PCR indicated that
      expression of the 660-bp sequence can be detected in 65% of the positive tumors.
      We were also able to identify in breast cancer DNA a segment of 1.6 kb comprising
      LTR and env gene sequences, which are homologous to MMTV, but not to the HERs.
      The origin of the MMTV-like sequences in tumor DNA could be the result of
      integrated MMTV-like sequences derived from a human mammary virus.

PMID- 9152516
TI  - Inhibitory effect of selenite and other antioxidants on complement-mediated
      tissue injury in patients with epidemic hemorrhagic fever.

PMID- 9152518
TI  - Biomarkers--the new frontier in the pathology of invasive and preinvasive
      neoplasias.
AB  - The papers in this symposium were presented at the 1996 Annual Meeting of the
      Biological Stain Commission. The authors hope that the discussion of biomarkers
      in the papers included in this issue and the literature reviewed in them will be
      useful to diagnostic pathologists as well as to investigators studying neoplastic
      processes in general.

PMID- 9152519
TI  - The status of immunohistochemical studies in lymphoma diagnosis.
AB  - Immunohistochemical studies of formalin fixed paraffin embedded sections today
      constitute an essential component of the diagnostic process for malignant
      lymphoma. Lineage related markers are of value in distinguishing various
      lymphomas from anaplastic large and small cell carcinomas, and from sarcomas.
      Other more recently available markers are of value in establishing prognosis and,
      on occasion, in differentiating between neoplastic and reactive proliferations.
      Meticulous attention to reagent control and technical procedures is essential to
      all such studies.

PMID- 9152520
TI  - Cell proliferation indexes: a biomarker in solid tumors.
AB  - Clinical studies have shown that carcinogenesis is linked to the development of
      proliferative abnormalities. Proliferative activity has been found to have
      prognostic significance in a variety of human tumors. Because proliferative
      abnormalities can precede the occurrence of morphological abnormalities, their
      measurement could also serve as useful biomarkers for chemoprevention trials. The
      variety of techniques for measuring cell proliferation in routine sections
      include mitosis counting, AgNORs, DNA precursor uptake (bromodeoxyuridine), and
      immunohistochemical detection of cell cycle proteins (PCNA, Ki-67/MIB-1). It is
      essential that the virtues and limitations of these methods be examined to ensure
      collection of meaningful clinical data.

PMID- 9152521
TI  - Changes in biomarker expression in the development of prostatic adenocarcinoma.
AB  - In spite of the prevalence of prostatic adenocarcinoma, the development and
      natural history of this malignancy is poorly understood. This paper reviews the
      current knowledge of biomarker expression during the development and progression
      of prostatic adenocarcinoma. Emphasis is placed on the comparison of biomarker
      expression in benign prostatic epithelium, intraepithelial neoplasia (PIN), a
      putative preinvasive lesion, and prostatic adenocarcinoma. Within the benign
      epithelium, the proliferative potential is restricted to the basal cells as
      demonstrated by the expression of proliferating cellular nuclear antigen (PCNA).
      The strong expression of the bcl-2 protein, an inhibitor of a apoptosis, supports
      the concept that the basal cells or a subpopulation of the basal cells represent
      the stem cell of the epithelium. In addition, the strong expression of growth
      factor receptors such as the epidermal growth factor receptor (EGFr), p185erbB-2,
      p180erbB-3, and c-met suggests that the growth of the basal cells is regulated by
      autocrine or paracrine factors. The luminal cells express secretory products such
      as prostate specific antigen and prostatic acid phosphatase, but demonstrate
      little expression of PCNA as well as growth factor receptors and proto-oncogene
      products. These observations are consistent with the theory that the luminal cell
      population is derived from the differentiation of the basal cells. In contrast to
      the normal epithelium, PCNA expression is frequently detected in the dysplastic
      luminal cells of the PIN lesion. Likewise, strong expression of p185erbB-2,
      p180erbB-3 and the c-met proto-oncogene product is also detected in the luminal
      cells of PIN lesions. Other factors which are strongly expressed by the
      dysplastic luminal cells include the nm23-H1 gene product, tumor associated
      glycoprotein-72 (TAG-72), fatty acid synthetase (FASE) and proteolytic enzymes.
      These findings suggest that PIN lesions are derived from an impairment of the
      differentiation of basal cells. The majority of biomarkers such as PCNA, p185erbB
      2, P180erbB-3, TAG-72, nm23-H1 and FASE which are strongly expressed in PIN
      lesions are also expressed in prostatic adenocarcinoma supporting the concept
      that PIN is a preinvasive lesion. Mutations of the p53 tumor suppressor gene, as
      well as strong expression of transforming growth factor alpha and bcl-2 typically
      occur in advanced stage prostatic adenocarcinomas and therefore likely represent
      late events in the development of prostatic adenocarcinoma.

PMID- 9152522
TI  - The use of biomarker expression to characterize neoplastic processes.
AB  - Biomarkers have been used by pathologists to aid the diagnosis of tumors for
      almost three decades. Their use has resulted in the re-evaluation and
      reclassification of several types of tumors. Currently, biomarkers are required
      to differentiate certain specific tumors with similar histologic patterns.
      Additional uses of biomarkers in the characterization of neoplastic processes are
      discussed including their use is prognosis, detecting early neoplastic processes,
      identifying tumor recurrence, measuring the effectiveness of various therapies
      (surrogate end point biomarkers), and identifying targets for novel therapies
      including immunotherapy and gene therapy. We propose that these newer uses of
      biomarkers will be just as important to pathology in the future as the uses of
      biomarkers in diagnosis have been over the past two decades.

PMID- 9152523
TI  - Confocal optical sectioning for meiotic analysis in Oenothera species and
      hybrids.
AB  - We present a photomicrographic technique for analysis of meiosis in Oenothera
      species and hybrids. In many species, the 14 isomorphic, 1-2 microns chromosomes
      are organized into a permanent translocation ring. Interspecific hybrid meiotic
      analysis is complicated by variations in homology between chromosome sets (Renner
      complexes) of allospecific origin. Though most wild species from complete rings
      of 14 at meiosis, hybrids often form combinations of smaller rings and bivalents.
      There is evidence that asynapsis (chain and univalents) also frequently occurs in
      hybrids. The greater complexity of hybrid meiotic organization can hinder
      resolution of individual chromosomes in such chains and small rings and encumber
      photomicrography of all chromosomes in a cell. Confocal laser scanning microscopy
      (CLSM) offers a new cytogenetic approach in ring-forming Oenothera species and
      hybrids. Fortunately, crystal violet, the stain classically used with this
      difficult material, fluoresces at an excitation wavelength of 488 nm and may thus
      be employed with the CLSM. Serial projection of image maxima from Z-axis confocal
      optical sections enables the investigator to count chromosomes and establish
      pairing relationships, regardless of chromosomal distribution.

PMID- 9152525
TI  - Scrotal pathology as the cause for hip pain. Diagnostic findings on bone
      scintigraphy.
AB  - Scrotal scintigraphy has become a relatively uncommon examination in many nuclear
      medicine departments. However, scrotal perfusion is visualized during three-phase
      bone imaging of the pelvis and hips. The authors present a compilation of three
      cases of hip pain secondary to unsuspected scrotal pathology documented on
      routine three-phase bone scintigraphy, discussing this topic for the first time
      in the literature. A short review of the pathophysiology of referred hip pain,
      differential diagnosis, and imaging alternatives emphasize the unique
      contribution of nuclear imaging.

PMID- 9152524
TI  - Adriamycin binds to the matrix of secretory granules during mast cell exocytosis.
AB  - The antineoplastic drug adriamycin induces exocytosis in rat peritoneal mast
      cells followed by a significant uptake of the drug into the secretory granules.
      The drug is fluorescent, allowing visualization of its accumulation and binding
      to mast cell granules by fluorescence microscopy. At the same time, the well
      known inorganic dye ruthenium red was used as a probe because of its great
      affinity for heparin in the mast cell secretory granules as visualized by bright
      field microscopy. Competition between adriamycin and ruthenium red for binding to
      the negatively charged matrix of granules was demonstrated. Biochemical studies
      were also performed to confirm microscopic observations. Adriamycin may be of
      interest for studying mast cell secretion; it is not only a strong fluorescent
      dye for mast cell granules that are in communication with the extracellular
      space, but it also induces mast cell exocytosis.

PMID- 9152527
TI  - Solitary adenocarcinoma metastasis mimicking sarcomatous degeneration in Paget's
      disease.
AB  - A rare case of mucinous adenocarcinoma presented as a solitary, metastatic
      deposit to a region of Paget's disease within the peripheral skeleton.
      Historical, physical, radiographic, and scintigraphic findings were
      indistinguishable from those of sarcomatous degeneration arising from pagetoid
      bone. This case supports the idea that when a painful, osteolytic lesion is
      discovered within a region of Paget's disease, bone scintigraphy has greater
      value of disclosing potential multifocal or multicentric disease than for
      providing etiologic specificity for the principal lesion.

PMID- 9152526
TI  - Kidney swelling. Findings on DMSA scintigraphy.
AB  - OBJECTIVE: To develop criteria identifying swollen kidneys on dimercaptosuccinic
      acid (DMSA) renal scintigraphy in acute pyelonephritis with regard to the DMSA
      distribution pattern, kidney functional size, and radioactive uptake. SUBJECTS
      AND METHODS: Thirty-eight children aged 15 days to 7 years with known
      pyelonephritis were examined with DMSA renal scintigraphy. All children were
      observed 2 or 3 times. In total, 94 scintigrams were evaluated. Qualitative and
      quantitative criteria for swelling were defined. RESULTS: Thirty-one observed
      kidneys satisfied the criteria of swelling. Quantitatively, kidney length and
      width/length were greater in swollen kidneys. Kidney uptake in percent of
      injected dose and kidney uptake/background were lower in swollen kidneys.
      Qualitatively, focal radioactive uptake defects known from a previous examination
      were sometimes obscured by swelling, and reappeared at follow-up. In 5 children
      with signs of swelling on repeat imaging, scintigraphy reinfection at the time of
      swelling was verified. CONCLUSIONS: Swollen kidneys may be the only sign of acute
      pyelonephritis on DMSA scintigraphy and swelling may obscure focal radioactive
      uptake defects. Measurement of kidney size and radioactive uptake can help
      identify swollen kidneys at DMSA scintigraphy and disclose acute pyelonephritis
      in the absence of overt clinical symptoms.

PMID- 9152529
TI  - Cholescintigraphy in the diagnosis of Rotor syndrome.
AB  - A 2-year-old boy with Rotor syndrome was studied with Tc-99m N-(di
      isopropylphenyl carbamoylmethyl) iminodiacetic acid (DIPA). In this patient, the
      liver was not visualized, and there was persistent visualization of the cardiac
      blood pool and along with prominent kidney excretion. It is concluded that Tc-99m
      DIPA cholescintigraphy may be helpful in the diagnosis of Rotor syndrome.

PMID- 9152528
TI  - Gastric emptying of milk feedings in infants and children. Anterior versus
      conjugate counting.
AB  - The radionuclide milk scan is a valuable tool for the evaluation of
      gastroesophageal reflux and gastric emptying in children. There is uncertainty as
      to whether anterior imaging alone is sufficient for determining gastric emptying
      in these patients. METHODS: Twenty-five children underwent Tc-99m sulfur colloid
      milk scans with images acquired in the anterior and posterior projections.
      Calculations of the 1 hour and 2 hour percentage of gastric residual activity
      were performed using the anterior counts alone and the geometric mean of the
      anterior and posterior counts. The anterior and posterior images were visually
      assessed for the presence of gastroesophageal reflux. RESULTS: The means of the
      absolute differences at 1 and 2 hours for the two methods of gastric residual
      calculation were 4.1% +/- 2.1% and 3.4% +/- 2.8%, respectively. There was good
      correlation between the two methods at 1 and 2 hours with r values of 0.991 and
      0.997 respectively. Gastroesophageal reflux was more obvious in the anterior
      images and three small episodes were only seen on the anterior view. CONCLUSION:
      Anterior images alone give reliable results for the determination of gastric
      emptying, and gastroesophageal reflux is more readily visualized anteriorly in
      the pediatric population.

PMID- 9152530
TI  - Radioiodine bronchogram in acute respiratory tract infection.
AB  - In this article, the authors described a 31-year-old woman with differentiated
      thyroid cancer is presented who had radioiodine uptake in the distribution of the
      tracheobronchial tree in association with symptoms of an acute respiratory tract
      infection. As expected, the uptake was transient and disappeared on the follow-up
      scan performed after 10 days of antibiotic treatment

PMID- 9152531
TI  - Sites of tuberculous involvement in patients with AIDS. Autopsy findings and
      evaluation of gallium imaging.
AB  - The purpose of this study was to review autopsy and gallium scan findings in two
      different acquired immune deficiency syndrome (AIDS) patient populations who had
      a confirmed diagnosis of tuberculosis (TB) to identify organs involved and
      accuracy of clinical diagnosis. The first group was comprised of 29 autopsies
      between January 1982 and December 1994, including only 18 patients who were
      diagnosed before death. Organs most commonly involved were the lymph nodes (59%),
      lungs (56%), spleen (53%), liver (45%), and kidneys (37%). Other opportunistic
      infections were present in 18 (59%) of autopsies, with more than one
      opportunistic infection present in 11 (37%) of the autopsies. Lungs were involved
      in 79% of all autopsies. The second population group included 94 patients with
      AIDS with a proven diagnosis of TB, only 24 of whom had gallium scans in the
      period between January 1992 and December 1994. Chest x-ray results were negative
      in 4 patients (17%); gallium scan results were positive in 16 patients (66%). The
      reasons for false-negative gallium scan results were due to anti-tuberculous
      treatment for periods varying from 2-21 months in 7 patients or the presence of
      extra pulmonary tuberculosis. The sites of TB involvement in the chest were: lung
      parenchyma in 5 patients (19%, 4 in mid and lower lung, and 1 in upper fields).
      There was lymph node involvement in all 16 patients (24 locations with
      mediastinal involvement in 23%, supraclavicular 23%, axillary 11%,
      retroperitoneal 11%, and inguinal region in 4%. We conclude that (1) tuberculosis
      in patients with AIDS behaves similar to primary tuberculosis; (2) the
      combination of chest x-ray and gallium imaging is sensitive for the diagnosis of
      pulmonary tuberculosis in patients with AIDS; (3) the involvement of mediastinal
      lymph nodes in gallium scans in the presence or absence of chest x-ray
      abnormalities should raise the possibility of TB involvement in patients with
      human immunodeficiency virus; (4) anti-TB treatment decreases the sensitivity of
      gallium scan.

PMID- 9152532
TI  - In-111 pentetreotide scintigraphy in patients with neuroblastoma. Comparison with
      I-131 MIBG, N-Myc oncogene amplification, and patient outcome.
AB  - OBJECTIVE: 1. To evaluate the relative efficacy of In-111 pentetreotide and 1-131
      radioiodinated meta-idobenzyl guanidine (MIBG) for detection of primary and
      metastatic neuroblastoma. 2. To assess the prognostic value of In-111
      pentetreotide uptake. METHODS AND MATERIALS: Seven In-111 pentetreotide and seven
      I-131 MIBG scans were obtained in six patients with stage IV neuroblastoma and 1
      with stage III ganglioneuroblastoma. Three scans were obtained at initial staging
      and four were obtained during therapy. Correlation was made with concomitant
      computed tomography scans, bone scans, N-myc oncogene amplification, and clinical
      outcome. RESULTS: Primary tumor was present in six patients and had been resected
      in 1. In-111 pentetreotide uptake was seen in two of six primary tumors, I-131
      MIBG scan was positive in five of six. In-111 pentetreotide scan was positive in
      two of four patients with bone metastases, I-131 MIBG scan was positive in three
      of four. Both showed liver metastases in one patient and did not show bone marrow
      metastases in another. Overall sensitivity for primary or metastatic disease was
      57% (four of seven) for In-111 pentetreotide and 86% (six of seven) for MIBG.
      Correlation between N-myc oncogene and In-111 pentetreotide uptake was seen in
      four of seven patients. In-111 pentetreotide uptake correlated with the clinical
      outcome in six patients with more than 1 year follow-up. Two patients with
      negative In-111 pentetreotide scans had unfavorable outcome. One patient died,
      and the other had local recurrence 15 months after diagnosis. Four patients with
      a positive scan are alive without disease on follow-up at 13-31 months after
      diagnosis. CONCLUSION: In-111 pentetreotide scintigraphy is less sensitive than I
      131 MIBG for detecting active neuroblastoma. In-111 pentetreotide uptake on
      scintigraphy may correlate with the prognosis. However, a larger series of
      patients is needed for further evaluation.

PMID- 9152533
TI  - Scintigraphic demonstration of a mobile gallbladder.

PMID- 9152534
TI  - Battered child syndrome. Uncommon pelvic fractures detected by bone scintigraphy.

PMID- 9152535
TI  - Interictal and ictal SPECT in a neonate with hemimegalencephaly.

PMID- 9152537
TI  - Rupture of a popliteal cyst visualized by radionuclide venography and confirmed
      by radionuclide arthrography.

PMID- 9152536
TI  - Extrarenal accumulation of Tc-99m DTPA in a gluteal abscess.

PMID- 9152538
TI  - Scintigraphic findings in Klippel-Feil syndrome.

PMID- 9152539
TI  - Tc-99m HMDP and Ga-67 imaging along with CT and MRI in fibrous dysplasia of the
      temporal bone.

PMID- 9152540
TI  - Visualization of bone structure with Tc-99m MIBI in a patient on hemodialysis.

PMID- 9152541
TI  - Metastatic disease to the thoracic spine. Simultaneous In-III WBC and bone scan
      findings after radiation therapy.

PMID- 9152542
TI  - Tc-99m MDP uptake in Staphylococcus aureus paraspinal abscess. Value of bone
      SPECT and reprojectional display in preoperative guidance.

PMID- 9152543
TI  - Brain SPECT imaging in a patient with epilepsy and memory dysfunction.

PMID- 9152544
TI  - Reflux into redundant duodenal stump of pancreatic allograft imitates duodenal
      stump leak on Tc-99m MAG3 imaging.

PMID- 9152545
TI  - Pentavalent Tc-99m DMSA accumulation in a medullary carcinoma of the thyroid.

PMID- 9152546
TI  - Diffuse F-18 FDG uptake in chronic thyroiditis.

PMID- 9152547
TI  - Ga-67 citrate and Tc-99m MDP uptake in peritoneal metastases from a poorly
      differentiated adenocarcinoma of gynecologic origin.

PMID- 9152548
TI  - Tc-99m MDP uptake in a calcified untreated non-Hodgkin's lymphoma of spleen.

PMID- 9152549
TI  - Current readings in nuclear medicine.

PMID- 9152550
TI  - The future of pediatric cardiology: is there one?

PMID- 9152551
TI  - Chromosomes 22q11 deletion syndrome: an update and review for the primary
      pediatrician.
AB  - Chromosome 22q11 deletion syndrome is a relatively newly described syndrome that
      encompasses the majority of patients previously felt to have velo-cardio-facial
      syndrome, DiGeorge syndrome, and conotruncal anomaly face syndrome. The disorder
      is characterized by a deletion of band 11 on the long arm of chromosome 22 most
      often recognized by fluorescent in situ hybridization (FISH) techniques.
      Extensive laboratory investigations are currently ongoing to uncover the specific
      genes involved and their functions. Phenotypically, individuals present with
      congenital heart disease, palatal abnormalities, facial dysmorphism, and
      developmental delay, as well as variable degrees of immunodeficiency,
      hypocalcemia, and endocrine abnormalities. The primary care physician has an
      important role in caring for these patients and their families. We review the
      current state of knowledge regarding chromosome 22q11 deletion syndrome, with an
      emphasis on the clinical presentation and on prevention and treatment of the
      known complications associated with this multisystem disorder. Chromosome 22q11
      deletion syndrome can be inherited in an autosomal dominant fashion or result
      from a de novo deletion or translocation. Hence, this syndrome may have
      significant reproductive risks to affected individuals and families.

PMID- 9152552
TI  - Influence of cholesterol screening and nutritional counseling in reducing
      cholesterol levels in children. The American Heart Association.
AB  - The purpose of this study was to determine whether cholesterol screening and
      nutritional counseling can reduce cholesterol concentrations in populations of
      otherwise unrecognized hypercholesterolemic children. A large pediatric practice
      in Parma Heights, Ohio, has conducted cholesterol surveillance of children over 2
      years of age since 1986. The importance of cholesterol and other recognized risk
      factors for the progression of atherosclerosis is discussed with all families,
      and the American Heart Association's Step-One diet is recommended. The present
      study examines data from a cohort of 894 children (473 boys, 421 girls) who had
      cholesterol concentrations above 185 mg/dL (4.79 mmol/L) (the 90th percentile) at
      baseline and, after counseling, had a repeat measurement an average of 2.2 years
      later. Their mean ages were 7 years at the first testing and 9.2 years at the
      second. Children who had cholesterol concentrations above 200 mg/dL (5.18 mmol/L)
      (the 95th percentile) had lipoprotein profiles done, and if their LDL cholesterol
      exceeded 130 mg/dL (3.37 mmol/L) (the 95th percentile), they were referred to a
      nutritionist, and family members were advised to have their blood lipids
      analyzed. Mean cholesterol concentration for all 894 children over this time
      period decreased by 9.4% (19.5 mg/dL [0.51 mmol/L]; 95% CI = 17.5 mg/dL [0.45
      mmol/L] to 21.5 mg/dL [0.56 mmol/L]; P < 0.001). A similar decrease of 8.6% (16.6
      mg/dL [0.43 mmol/L); 95% CI = 14.0 mg/dL [0.36 mmol/L] to 19.3 mg/dL [0.50
      mmol/L); P < 0.001) was observed for the 463 children who had initial cholesterol
      concentrations between 185 and 200 mg/dL (4.79 and 5.18 mmol/L) and who therefore
      received a less intense intervention. Cholesterol concentrations in groups of
      otherwise unidentified hypercholesterolemic children can be significantly reduced
      as a result of cholesterol screening and nutritional counseling in a pediatric
      practice setting.

PMID- 9152553
TI  - The 1996 U.S. Preventive Services Task Force Report: what's no longer worth
      doing?
AB  - How often does a report tell clinicians what they no longer need to do? In this
      era of increasing managed care, primary care physicians are seemingly being asked
      to do more and more. Therefore, it's worth taking note of the new U.S. Preventive
      Services Task Force Report and the 11 interventions pertaining to pediatrics this
      document suggests could be dropped without sacrificing quality of care. In
      addition, a listing is included of the newly added chapters in this report that
      are of potential interest to pediatricians.

PMID- 9152554
TI  - Maternally reported fetal activity levels and developmental diagnoses.
AB  - Retrospective maternal report of fetal activity level was compared with
      developmental diagnosis in 608 consecutively referred children. Maternal history
      of fetal activity level was also obtained from 140 unmatched well children in a
      general pediatric clinic. Fetal hyperactivity was positively associated with a
      diagnosis of child hyperactivity, and fetal hypoactivity was positively
      associated with a diagnosis of mental retardation in the children. Maternal
      histories of fetal activity level in the control group weakened the strength of
      the association between fetal hyperactivity and child hyperactivity but did not
      affect the association between fetal hypoactivity and mental retardation in
      children.

PMID- 9152555
TI  - The first chest radiograph in neonates exhibiting respiratory distress at birth.
AB  - The aim of the present study was to assess the diagnostic accuracy and clinical
      utility of the first anteroposterior chest radiograph taken within the first
      hours of life from 99 neonates admitted consecutively from the delivery room to
      the neonatal intensive care unit because of mild to moderate respiratory
      distress. Before the radiograph was taken, all necessary emergency life support
      measures were undertaken. These included intubation, if indicated, and placement
      of intravenous and intra-arterial cannulae and nasogastric tubes. Intratracheal
      surfactant was never, however, administered before the radiograph. We examined
      the agreement between the clinicians' and the pediatric radiologist's opinion
      regarding the pulmonary and cardiac findings in these radiographs. Seventy-four
      radiographs exhibited definite pulmonary or cardiac pathology. In 66 patients the
      initial assessment was in agreement with the radiologic reevaluation. Clinicians'
      and radiologist's diagnoses of respiratory distress syndrome (RDS) agreed in 95%,
      of pneumothoraces in 78%, but, ultimately, of transient tachypnea of the neonate
      (TTN) in only 48%. The benefits of having the chest radiographs reviewed by a
      consultant radiologist experienced in neonatology are evident. The first chest
      radiograph taken early during the course of the disease had the greatest impact
      in the care of neonates with mild respiratory distress. In such cases,
      potentially dangerous conditions (e.g., pneumothoraces) could be detected before
      severe clinical deterioration occurred.

PMID- 9152556
TI  - Propofol sedation for terminal care in a pediatric patient.

PMID- 9152557
TI  - Autoimmune enteropathy in a pediatric patient: partial response to tacrolimus
      therapy.

PMID- 9152558
TI  - Staphylococcal meningitis secondary to sacral osteomyelitis in an infant.

PMID- 9152559
TI  - Diagnostic and therapeutic tympanocentesis.

PMID- 9152560
TI  - Aspiration of a tooth in a patient with a tracheostomy.

PMID- 9152561
TI  - Protease inhibitors: a therapeutic breakthrough for the treatment of patients
      with human immunodeficiency virus.
AB  - As one of the largest growing classes of antiretroviral drugs, protease
      inhibitors are promising agents for the management of patients infected with the
      human immunodeficiency virus (HIV). We reviewed the literature and compared
      efficacy, dosing, side effects, and drug-interaction profiles of the protease
      inhibitors saquinavir, ritonavir, indinavir, and nelfinavir. We addressed the use
      of these antiprotease agents as monotherapy versus use in combination therapy
      with other antiretroviral medications, and the potential for HIV to develop
      resistance to this drug class. We also discussed therapy with dual protease
      inhibitors and the use of protease inhibitors in pregnant or lactating women and
      in pediatric patients. Finally, we examined case reports of the addition of
      protease inhibitors to an antiretroviral regimen that ultimately decreases or
      reverses opportunistic infections.

PMID- 9152562
TI  - The nonnarcotic antitussive drug dimemorfan: a review.
AB  - The antitussive dimemorfan phosphate was discovered through extensive screening
      of morphinic derivatives and was introduced in Japan in 1975. The majority of
      studies on dimemorfan have been published in Japanese, and this review aims to
      make these data more generally available. The antitussive action of dimemorfan
      appears to be directly on the cough center in the medulla. Dimemorfan does not
      induce any significant physical or psychologic dependence, and its antitussive
      action is not affected by the opioid-receptor blocker levallorphan. Dimemorfan is
      therefore considered a nonnarcotic antitussive. Studies of antitussive effects in
      animal models indicate that dimemorfan is up to three times more potent than
      codeine and is equivalent to dextromethorphan. Three major comparative clinical
      trials and postmarketing surveillance studies showed that dimemorfan is equally
      or slightly more efficacious than dextromethorphan, benproperine phosphate, or
      placebo for the control of coughing. Several animal and clinical studies have
      confirmed the efficacy and safety of dimemorfan. Dimemorfan was effective in the
      majority of patients. In contrast to the narcotic antitussives, dimemorfan caused
      no serious problems with the digestive system, such as constipation and disorders
      of the bile duct, caused no dependence or tolerance, and was unlikely to have
      clinical analgesic effects. Minor side effects, such as loss of appetite, nausea,
      and drowsiness, were seen in less than 10% of patients. A syrup formulation of
      dimemorphan that retains its efficacy and safety is also available. Overall,
      these data indicate that dimemorfan is an effective nonnarcotic antitussive agent
      with a low incidence of adverse events.

PMID- 9152563
TI  - Loratadine in the treatment of urticaria.
AB  - Urticaria is a common skin disease, which in its chronic form, is a very
      disturbing condition. Because histamine is the best-documented chemical mediator
      of urticaria, histamine-antagonists are the mainstay of therapy. First-generation
      antihistamines are limited by their tendency to produce sedation and
      anticholinergic side effects. Most of the newer second generation antihistamines
      compare well with the earlier agents in efficacy but are not limited by the same
      adverse side effects. Loratadine may be distinguished from other second
      generation antihistamines by its pharmacodynamic profile, as well as its
      tolerability and safety.

PMID- 9152564
TI  - Efficacy and tolerability of finasteride in symptomatic benign prostatic
      hyperplasia: a primary care study. Primary Care Investigator Study Group.
AB  - Because increasing numbers of men are seeking treatment for benign prostatic
      hyperplasia (BPH) from primary care physicians, we sought to assess the efficacy
      and tolerability of finasteride in a primary care setting. In this randomized,
      double-masked study, 2,112 men with symptomatic BPH received either finasteride
      (n = 1,589) or placebo (n = 523) for 1 year. At 3, 6, 9, and 12 months, urinary
      symptoms were measured using the American Urological Association Symptom Index
      (AUASI). Quality of life was assessed using the BPH Impact Index (BII), which
      assessed bother, worry, physical discomfort, and restriction in activities. Both
      patients and investigators assessed overall urologic status. Investigators
      assessed the effect of the drug on plasma lipids in a subset of patients.
      Patients treated with finasteride had a statistically significant mean decrease
      in AUASI scores compared with patients treated with placebo beginning at month 6
      and continuing throughout the study. At month 12, adjusted mean decreases in
      AUASI scores were -4.96 for finasteride versus -3.71 for placebo. Statistically
      significant differences in favor of finasteride were also noted on BII at months
      9 and 12. Patient and investigator overall assessments showed greater improvement
      in the finasteride group beginning at month 6. The incidence of drug-related
      sexual adverse experiences was significantly greater in finasteride-treated
      patients but led to withdrawal in only 2.2% of these patients. Overall lipid
      profile was not significantly altered in either group. Based on improvement in
      symptoms and quality of life, and on its favorable tolerability profile,
      finasteride should be considered by primary care physicians for management of
      symptomatic BPH.

PMID- 9152565
TI  - Ketorolac, prednisolone, and dexamethasone for postoperative inflammation.
AB  - This 6-week, partially masked, three-arm, multicenter study was conducted to
      evaluate the postoperative anti-inflammatory efficacy of ketorolac, a
      cyclooxygenase inhibitor. The study setting was the clinical practice of six
      ophthalmic surgeons. The study enrolled 157 candidates for routine extracapsular
      cataract extraction or phaco-emulsification and posterior-chamber intraocular
      lens implantation. Patients who received any glucocorticoid or cyclooxygenase
      inhibitor within 1 week of surgery were excluded. All patients were treated with
      solutions of 0.5% ketorolac, 1% prednisolone acetate, or 0.1% dexamethasone
      instilled into the operative eye three times daily from 1 day before surgery to 4
      weeks after surgery. Efficacy variables included the signs of anterior-segment
      inflammation, primarily cells and flare in the anterior chamber, as observed by
      slit-lamp biomicroscopy; fluorescein leakage across the blood-aqueous barrier as
      measured by fluorophotometry; and the rating of efficacy by the investigator. No
      significant differences were seen between ketorolac and either glucocorticoid in
      cells and flare. No significant differences were found in other signs of
      inflammation, except conjunctival hyperemia and Descemet's folds at week 2.
      Ketorolac showed significantly greater efficacy than the glucocorticoids against
      blood-aqueous barrier breakdown at day 5 and week 2, as demonstrated by the
      difference in fluorescein concentration between the operated and nonoperated
      eyes. Investigators did not detect any significant difference in rating for
      overall effectiveness and acceptability. These findings support the use of
      ketorolac as an alternative to glucocorticoids for the treatment of postoperative
      inflammation.

PMID- 9152566
TI  - The effect of fluticasone propionate aqueous nasal spray on eosinophils and
      cytokines in nasal secretions of patients with ragweed allergic rhinitis.
AB  - Cytokines active on eosinophils are important in the pathogenesis of allergic
      diseases. A study was conducted to determine if nasal eosinophilia in allergic
      rhinitis is associated with an increase in eosinophil-active cytokines in nasal
      secretions and to compare the effects of fluticasone propionate aqueous nasal
      spray with astemizole and placebo on the levels of these cytokines. Forty-five
      patients with moderately severe ragweed allergic rhinitis were randomly assigned
      to receive 2 weeks of treatment with fluticasone propionate aqueous nasal spray
      200 micrograms once daily, astemizole 10 mg once daily, or placebo. Nasal lavage
      was performed in July (preseason), August (peak season), September (after 2 weeks
      of treatment), and October (postseason). The number of eosinophils, the amount of
      eosinophil-derived neurotoxin (EDN), and the amount of eosinophil survival
      enhancing activity were measured. Total mean nasal symptom scores, concentrations
      of nasal eosinophils and EDN, and eosinophil survival-enhancing cytokine activity
      in nasal secretions were significantly lower after 2 weeks of treatment with
      fluticasone propionate compared with astemizole or placebo. Survival-enhancing
      activity was detected in the nasal secretions of 25 patients. By blocking
      activity with monoclonal antibodies, specific cytokines were identified
      (granulocyte macrophage-colony stimulating factor, 3 samples; interleukin-3, 2
      samples; interleukin-5, 5 samples). In conclusion, eosinophil-active cytokine
      concentrations parallel the nasal symptoms of patients with ragweed allergic
      rhinitis. Unlike astemizole, fluticasone propionate significantly lowers cytokine
      activity in nasal tissue, which may contribute to the therapeutic efficacy of the
      drug.

PMID- 9152567
TI  - PROTECT interim results: a large multicenter study of patients with type II
      diabetes. Precose Resolution of Optimal Titration to Enhance Current Therapies.
AB  - The Precose Resolution of Optimal Titration to Enhance Current Therapies
      (PROTECT) study is an ongoing Phase IV clinical trial designed to assess the
      effectiveness, tolerability, and safety of acarbose tablets in patients with type
      II diabetes when the dosage is slowly titrated upward. This multicenter, open
      label, 28-week trial will enroll approximately 7,000 type II diabetic patients.
      The present report describes the interim results for 2,139 patients who completed
      the trial as of November 1, 1996. Patients with type II diabetes enrolled in the
      study were inadequately controlled either with diet alone or with a sulfonylurea.
      The dosage of acarbose was titrated from 25 mg three times a day (TID) to 100 mg
      TID based on tolerability and efficacy. Efficacy of glycemic control was assessed
      by changes in glycated hemoglobin A1c (Hb A1c) and 1-hour postprandial plasma
      glucose (PPG) levels. Tolerability and safety were determined by patient reports
      of treatment-emergent adverse events and by review of laboratory tests. The
      PROTECT study confirms the previously demonstrated efficacy and safety of
      acarbose in improving glycemic control in patients with type II diabetes
      regardless of a patient's age, body weight, ethnic background, time since
      diagnosis, or severity of disease. mean 1-hour PPG levels declined throughout the
      entire treatment period, with a mean decrease from baseline of -47 mg/dL at the
      end of treatment. Hb A1c, the most reliable indicator of long-term glycemic
      control, decreased over the course of treatment, resulting in a mean decrease of 
      0.7% (P < 0.001). Although all patient types enrolled in the study responded
      positively to therapy, certain subgroups responded particularly well, such as
      those patients diagnosed with the disease less than 1 year ago, those treated
      with acarbose as monotherapy, and those with higher baseline Hb A1c levels.
      Adverse events were experienced by 36% of all patients and consisted primarily of
      gastrointestinal disturbances (flatulence, diarrhea, abdominal pain). Moderate
      renal insufficiency (serum creatinine levels between 1.5 and 2 mg/dL) was present
      in 259 patients, and no patients developed serum hepatic transaminase levels more
      than twice the normal range.

PMID- 9152568
TI  - The effect of food intake on the pharmacokinetics of sustained-release morphine
      sulfate capsules.
AB  - The effect of food intake on the pharmacokinetics of sustained-release (SR)
      morphine sulfate capsules was assessed in 24 healthy male volunteers. Subjects
      were randomized to receive a single, 20-mg SR morphine sulfate capsule while
      fasting and immediately after consumption of a standard high-fat meal. Plasma
      samples were masked for pharmacokinetic analysis. Although the extent of
      absorption of the SR preparation was comparable in subjects in the fed and fasted
      states, plasma morphine concentrations were significantly lower at most sampling
      times up to 10 hours when the drug was administered after a high-fat meal. The
      rate of absorption of morphine from the SR capsule was slower with food intake as
      evidenced by a 13% decrease in the maximum concentration (Cmax), a 28% increase
      in the half-life of absorption, and a 19% increase in the time to Cmax. Results
      of this study indicate that food intake had an effect on the overall plasma
      concentration-versus-time profile of the SR morphine sulfate oral preparation,
      the extent of which was not revealed by a comparison of Cmax and area under the
      plasma concentration-time curve values alone.

PMID- 9152569
TI  - Effects of estrogen replacement therapy on rates of cyclic alternating patterns
      and hot-flush events during sleep in postmenopausal women: a pilot study.
AB  - The objective of this pilot study was to evaluate the effects of conjugated
      estrogens on the rates of cyclic alternating patterns of sleep (CAPS) and
      nocturnal hot flushes in symptomatic postmenopausal women. Seven postmenopausal
      or posthysterectomy women aged 45 to 60 years with nocturnal diaphoresis and/or
      hot flushes participated in this study. The study was conducted with a single
      masked design using a matching placebo. The placebo baseline was followed by a 4
      week, single-masked treatment of conjugated estrogens 0.625 mg taken 4 hours
      before bedtime. Each patient's sleep was monitored in the laboratory for 3
      consecutive nights during placebo baseline and again for 3 consecutive nights
      after an at-home period of at least 24 days of estrogen replacement therapy.
      Estrogen therapy resulted in a statistically significant decrease in the overall
      number of hot flushes and the number of hot hot flushes associated with
      awakenings, as well as improvement in sleep efficiency and a reduction in the
      rate of CAPS. These data confirm earlier well-established reports that estrogens
      reduce the frequency of hot flushes and suggest that the frequency of nocturnal
      arousals decreases and sleep quality improves in conjunction with a reduction in
      the rate of CAPS.

PMID- 9152570
TI  - Economic evaluation of zuclopenthixol acetate compared with injectable
      haloperidol in schizophrenic patients with acute psychosis.
AB  - Zuclopenthixol acetate is a rapid-acting, injectable neuroleptic drug with a
      duration of action that allows for administration once every 2 to 3 days, in
      contrast to injectable haloperidol, which may require administration more than
      once daily. To assess the place of zuclopenthixol acetate in the treatment of
      acute episodes of schizophrenia, a cost-consequence analysis was performed
      comparing this new medication with short-acting, injectable haloperidol. The
      perspective of the Quebec health care system was adopted. The study population
      comprised patients diagnosed with schizophrenia who experienced an acute episode
      of psychosis and who were treated with intramuscular (i.m.) haloperidol. The
      study assessed patients for 9 days after the start of treatment. The literature
      was the principal source of comparative data about the clinical outcomes of the
      two treatments. The total cost associated with zuclopenthixol acetate i.m. or
      haloperidol i.m. was modeled using a decision tree built around the number of
      i.m. injections required to achieve stabilization. To establish costs, expert
      panels were consulted and patients' files were reviewed for a sample of
      schizophrenic patients who had been hospitalized in a large psychiatric or
      general hospital subsequent to a visit to the emergency department and had
      received a short-acting i.m. neuroleptic drug. Only a direct medical records
      costs were considered. Because zuclopenthixol acetate was not on the market at
      the time of the study, the file review did not allow for a direct estimate of its
      related costs but did provide an account of haloperidol use. The literature shows
      that zuclopenthixol acetate is similar to haloperidol with respect to the control
      of psychotic episodes; however, zuclopenthixol acetate is associated with
      increased sedation and a lower incidence of extrapyramidal symptoms. Using the
      base-case estimate for the number of injections required for stabilization, the
      incremental cost of zuclopenthixol acetate 50 mg over haloperidol was $25.00
      (1995 Canadian dollars) per patient at the psychiatric hospital and $21.00 per
      patient at the general hospital. The results were sensitive to the estimate of
      the number of injections and the number of minutes of nursing care required by
      agitated patients. Zuclopenthixol acetate resulted in cost savings over
      haloperidol if it permits a reduction of 25% in minutes of nursing care or if 85%
      of patients require 2 injections or less (45% requiring 1 injection and 40%
      requiring 2). However, whichever drug is used, the cost of the injectable
      neuroleptic represents a small fraction of the cost of care for acutely psychotic
      patients.

PMID- 9152571
TI  - The economic impact of the tacrine in the treatment of Alzheimer's disease.
AB  - Alzheimer's disease is a progressive neurodegenerative disorder that results in
      tremendous economic and quality-of-life burdens. This paper presents estimates of
      the impact of tacrine use on the costs of caring for patients with Alzheimer's
      disease. This study presents a cost analysis, based on a decision-analytic model
      constructed around the milestones in the progression of Alzheimer's disease.
      Clinical data concerning the effectiveness of tacrine came from published results
      of an open-label follow-up study of 663 patients originally enrolled in a placebo
      controlled clinical trial of tacrine. Data concerning longevity, nursing home
      time, and costs of community and nursing home care are taken from several reports
      based on prospective cohorts of patients. The use of tacrine was associated with
      a cost savings of $9,250 (7.5%) over the patient's lifetime from diagnosis to
      death, even when averaged over data from patients who discontinued tacrine
      treatment or took only low doses. Most of the savings were due to reduced time in
      nursing homes. Patients who continued higher doses of tacrine experienced a cost
      saving of more than $36,500 over 5 years. Model results persisted over a wide
      range of sensitivity analysis variations. The use of tacrine for patients with
      mild-to-moderate Alzheimer's disease reduces the costs of medical and social
      services required for care, and it increases functioning and delays nursing home
      placement for up to 433 days. New treatments that can both improve clinical
      outcomes and save costs should be given serious consideration by clinicians and
      administrators.

PMID- 9152572
TI  - The use of claims databases for outcomes research: rationale, challenges, and
      strategies.
AB  - Health care payers and policy makers need information about the cost and
      effectiveness of medical treatments. While randomized controlled trials
      historically are the primary source of medical information, they are expensive
      and labor-intensive, and often have limited utility for answering questions about
      "real-world" patient populations. These problems have led to an increasing
      reliance on claims database research in making policy decisions about treatment
      options. However, both researchers and decision makers should recognize the
      limitations and unique features of claims databases. Recommendations for avoiding
      or minimizing threats to internal validity, construct validity, and external
      validity are: (1) use of a study design that includes comparisons; (2) ensuring
      that the study design and conclusions are consistent with the database; (3) a
      priori conceptual modeling of the research question; (4) use of appropriate
      constructs; (5) explicit examination of alternative explanations for study
      findings; (6) sensitivity analyses of key assumptions; (7) awareness of the
      distinction between statistical and practical significance of findings; (8)
      generalization only when appropriate; and (9) reporting of relevant information.
      Given that any study design or data source has limitations, we hope that this
      paper will encourage a philosophy of methodological pluralism in outcomes
      research. Awareness and accurate reporting of validity issues will strengthen and
      extend the information resources currently available to decision makers.

PMID- 9152573
TI  - Multimodality cardiovascular image segmentation using a deformable contour model.
AB  - An automatic segmentation method has been developed for cardiovascular
      multimodality imaging. A "snake" model based on a curve shaping and an energy
      minimizing process is used to detect blood-wall interfaces on Cine-CT, MRI and
      ultrasound images. Deformation of a reduced set of contour points was made
      according to a discretized global, regional and local minimum energy criterion. A
      continuous regional optimization process was also integrated into the deformation
      model, it takes into account a cubic spline interpolation and adaptive regularity
      constraints. The constraints provided rapid convergence toward a final contour
      position by successively stopping spline segments.

PMID- 9152574
TI  - Edge-shrinking interpolation for medical images.
AB  - A new algorithm for interpolating the missing data between two adjacent medical
      images is presented. Our method is useful for solving the interpolation of any
      region-represented images of an object to be reconstructed, even when the object
      is stretched abruptly, branched or hollow, as often occurs in medical images,
      which cases can not be handled well by existing methods. When this algorithm is
      applied, the nonoverlapped regions of the same object in the two base images are
      first extracted and encoded by chamfer distance code on every pixel in these
      regions. Then, the outer edges of the nonoverlapping regions are shrunk inward
      simultaneously so that the stretched edges reach the edges of the overlapping
      regions at the same time. The distance codes in nonoverlapping regions are used
      to limit the shrinking of these edges in the interpolation process. The proposed
      method also provides object centralization and enlargement operations to obtain
      stable and reasonable results in complicated case. The experimental results show
      that the proposed method is more efficient in resolving general interpolation
      tasks than the existing methods (S.P. Raya and J. K. Udupa, IEEE Trans. Med.
      Image. 9, 32-42, 1990; G. T. Herman et al., IEEE Comput. Graph. Appl. 12, 69-79,
      1992; J.F. Guo et al., Comput. Med. Imag. Graph. 19, 267-279, 1995.)

PMID- 9152575
TI  - Measuring registration potential in planar transmission images.
AB  - One method of detecting change in an anatomical structure is by comparing
      elements of a longitudinal series of planar transmission images (i.e.
      radiographs). Unfortunately, changes in image formation parameters, such as
      patient placement, prevent successful image registration from occurring. In this
      paper, an analytic method is described which allows one to quantify the ability
      to register two planar transmission images. The concepts described in this paper
      are not dependent on a specific image registration method. In fact, these results
      hold independent of the registration algorithm used since they are based solely
      on phenomena occurring during the image formation process.

PMID- 9152576
TI  - MR angiography of intracranial aneurysms: a comparison of 0.5 T and 1.5 T.
AB  - The objective of this paper is to compare the diagnostic efficacy of 3 DFT time
      of-flight MR angiography (MRA) at middle-field-strength and high-field-strength
      in diagnosis of intracranial aneurysms. Thirty-one patients, including 26
      patients with angiographically confirmed intracranial aneurysms (n = 28),
      underwent MRA at 0.5 and 1.5 T. Images were interpreted by six trained observers
      who were blinded to diagnosis. Twelve projections of MRA of the circle of Willis,
      by maximum-intensity projection algorithm, were reviewed using continuous
      confidence-judgement scales. It was found that MRA at 1.5 T was more sensitive
      than that at 0.5 T in detection of aneurysms. The sensitivity of six observers
      ranged between 50 and 64% (mean 56%) at 0.5 T, and between 61 and 86 86% (mean
      75%) at 1.5 T. In the smaller aneurysms less than 5 mm, the differences between
      the units became greater. The sensitivity for small aneurysms ranged from 23 to
      54% (mean 32%) at 0.5 T, and from 31 to 69% (mean 58%) at 1.5 T. Our conclusion
      was that high field strength confers higher accuracy in the detection of
      intracranial aneurysms with MRA with current-generation MR imagers.

PMID- 9152577
TI  - MR hysterography using axial long TR imaging with three-dimensional projections
      of the uterus.
AB  - A rapid screening technique for the presentation of uterine cavity anatomy
      obtained with MR is described. MR hysterographic (MRHG) images were generated and
      evaluated for uterine cavity abnormalities. Six patients referred for MRI
      evaluation of the uterus for infertility had an MRI using a pelvic phased array
      coil with axial 3 mm interleaved fast spin echo images (TR 9000 ms, TE 288 ms
      with fat saturation) processed using maximum intensity projection algorithms to
      construct MRHG images. Using the conventional MR sequence as the gold standard
      the MRHG images were evaluated by two reviewers and accuracy calculated. MRHG
      took less than 3 min, demonstrated the correct diagnosis in all with a quality
      score of diagnostic to optimal, and with excellent interobserver agreement (kappa
      0.9).

PMID- 9152578
TI  - Arachnoid cysts and pneumosinus dilatans.
AB  - The association of intracranial arachnoid cysts and pneumosinus dilatans is
      considered to be relatively rare, and has previously been described in only a
      limited number of cases. In this study the CT and/or MRI examinations of a total
      of 30 cases with middle cranial fossa arachnoid cysts were retrospectively
      evaluated in an attempt to note any association with pneumosinus dilatans of the
      paranasal sinuses. In four patients with surgically treated, large, middle
      cranial fossa arachnoid cysts, obvious paranasal sinus changes, consistent with
      pneumosinus dilatans, were noted. The frequency of the association of arachnoid
      cysts and pneumosinus dilatans was approximately 13% (n = 4 out of 30 patients)
      in this series.

PMID- 9152579
TI  - Postmortem cryosectioning as an anatomic reference for human brain mapping.
AB  - This study examined the densitometric and topographic detail of high resolution
      3D digital postmortem cryosectioned brain images. Anatomic image data and
      histology from cryosectioned human brain were compared to in vivo MRI for the
      ability to delineate neuroanatomic structure. 3D surface reconstructions in the
      Talairach and Tournoux atlas ("Co-planar stereotaxic atlas of the human brain",
      Thieme, New York, 1988) coordinate system enabled morphometric comparisons for a
      representative sample of neuroanatomic structures. Spatial resolution of
      cryosection images averaged 200 and 170 microns/pixel for whole head and brain,
      respectively, and 40 microns/pixel for isolated the brain regions. Anatomic
      detail was far superior to MRI, particularly in deep subcortical regions such as
      the basal ganglia and in mesencephalic nuclei and tracts. Digital repositioning
      in the Talairach coordinate system enabled efficient structure localization and
      morphometric comparison. Histology from collected tissue sections provided
      cytologic detail that could be mapped to its approximate 3D context. This
      approach permits comprehensive morphometric analyses necessary for an anatomic
      framework to a digital atlas of the human brain.

PMID- 9152580
TI  - Seizure interference by medications: how big a problem?

PMID- 9152581
TI  - Energy dosing in ECT: threshold stimulation or formula?

PMID- 9152582
TI  - Stimulus dosing with ECT: to titrate or not to titrate--that is the question.

PMID- 9152583
TI  - ECT in acute delirium and related clinical states.
AB  - A retrospective investigation of electroconvulsive therapy (ECT)-treated patients
      in 1992-94 at the Psychiatric Hospital in Aarhus, Denmark showed that en bloc
      treatment had been given in 39 cases of 420 patient series. The basic diagnoses
      (according to ICD-10) were severe depressive disorder, bipolar affective disorder
      mixed state, manic disorder, acute transient psychotic disorder, schizoaffective
      disorder, and schizophrenia; all patients were in a severely psychotic condition.
      Eight patients were diagnosed with acute delirium. Delirious symptoms disappeared
      completely after the first few ECT treatments. Patients were subsequently given
      supplementary treatment for the underlying disease. ECT is an effective treatment
      for psychoses complicated by acute delirium.

PMID- 9152584
TI  - Strength Symmetry Index: a measure of seizure adequacy in ECT.
AB  - Seizure electroencephalography (EEG) was recorded from two channels--right (Rt)
      and left (Lt)--during bilateral electroconvulsive therapy (ECT) (n = 12) and
      unilateral ECT (n = 12). The EEG was also acquired into a microcomputer and was
      analyzed without knowledge of the clinical details. EEG recordings of both ECT
      procedures yielded seizures of comparable duration. The Strength Symmetry Index
      (SSI) was computed from the early- and midseizure phases using the fractal
      dimension of the EEG. The seizures of unilateral ECT were characterized by
      significantly smaller SSI in both phases. More unilateral than bilateral ECT
      seizures had a smaller than median SSI in both phases. The seizures also differed
      on other measures as reported in the literature. The findings indicate that SSI
      may be a potential measure of seizure adequacy that remains to be validated in
      future research.

PMID- 9152585
TI  - Use of electroconvulsive therapy in adolescents.
AB  - Electroconvulsive therapy (ECT) is used in adolescent psychiatric practice, yet
      few studies have been conducted to assess its use for 13-19-year-olds. Efficacy,
      indications, side effects, technical characteristics, and outcome are uncertain.
      We retrospectively reviewed the medical records of 21 adolescents treated with
      bilateral ECT in our department from 1984 through 1995. In our series, ECT was
      effective in treating both maniac and depressive episodes, with a high rate of
      relapse at 1 year follow-up (approximately 40%). Clinical improvement was only
      partial and in schizophrenia and schizoaffective episodes. Seizure threshold was
      associated with gender, but not with the cumulative number of treatments. Adverse
      effects were frequent, but were usually transient with only moderate discomfort,
      even in patients with concomitant medical problems. We conclude that ECT is a
      safe and effective treatment for adolescents with severe and intractable mental
      illness, and it has the same indications and effects as in adults.

PMID- 9152586
TI  - Transient postictal psychosis associated with a course of ECT.
AB  - Postictal psychoses, defined as episodic, time-limited psychiatric disturbances
      of diverse phenomenology, temporally related to a seizure or cluster of seizures,
      have been well described in patients with focal and generalized epilepsies.
      Although similar disturbances have been reported in patients undergoing
      electroconvulsive therapy (ECT), the syndrome of ECT-associated postictal
      psychosis has not been well described. We review the literature defining the
      syndrome of postictal psychosis (PIP) associated with the epilepsies, as well as
      reports of confusional and manic disturbances meeting accepted criteria for PIP,
      which have been reported to occur as complications of ECT. In addition, we report
      a case of delusional and hallucinatory psychosis associated with a course of ECT,
      also having the characteristics of a PIP. We conclude that time-limited
      psychiatric disturbances, phenomenologically (and possibly pathophysiologically)
      similar to the PIP of epilepsy can occasionally occur as complications of ECT,
      and that they may have confusional, manic, delusional, or hallucinatory symptoms.
      The implications of these occurrences for the use and continuation of ECT are
      discussed.

PMID- 9152587
TI  - Comments on the "half-age" method of stimulus dosing.

PMID- 9152588
TI  - Proposed titration schedule.

PMID- 9152589
TI  - Naloxone and ECT seizure length.

PMID- 9152590
TI  - Enterohepatic recirculation of trichloroethanol glucuronide as a significant
      source of trichloroacetic acid. Metabolites of trichloroethylene.
AB  - Trichloroacetic acid (TCA) is a metabolite of trichloroethylene (TRI) thought to
      contribute to its hepatocarcinogenic effects in mice. Recent studies have shown
      that peak blood concentrations of TCA do not occur until approximately 12 hr
      after an oral dose of TRI; however, blood concentrations of TRI reach a maximum
      within 1 hr and is nondetectable after 2 hr. The objective of this study was to
      examine quantitatively enterohepatic recirculation of trichloroethanol (TCEOH)
      and TCA as a possible mechanism responsible for the delayed production of TCA.
      Jugular vein, duodenum, and bile duct-cannulated Fischer 344 rats were used, with
      the collection of blood, bile, urine, and feces samples after intraduodenal and
      intravenous dosing of animals with TRI, TCEOH, and TCA. Samples were analyzed by
      GC for TCA, total TCEOH, and free TCEOH. The results show that, after an
      intravenous dose of TCEOH (100 mg/kg), 36% of the TCEOH in blood is attributable
      to enterohepatic recirculation. With the same treatment, 76% of the TCA in blood
      is attributable to enterohepatic recirculation of metabolites. Peak
      concentrations of total TCEOH in bile, after an intraduodenal dose of TRI, are
      over 5 times higher than peak concentrations of total TCEOH in systemic blood.
      Peak concentrations of TCEOH glucuronide in bile are approximately 200 times
      higher than peak concentrations of TCEOH glucuronide in systemic blood.

PMID- 9152591
TI  - Carrier-mediated hepatic uptake of the cationic cyclopeptide, octreotide, in
      rats. Comparison between in vivo and in vitro.
AB  - The plasma concentration and biliary excretion profiles of a cationic cyclic
      octapeptide, octreotide, were compared between control rats and rats given an
      intravenous infusion of a bile acid, taurocholate (TCA), and an organic anion,
      dibromosulfophthalein (DBSP). Both TCA and DBSP reduced the plasma elimination
      and biliary excretion of octreotide after its intravenous bolus administration.
      Two mechanisms accounting for this phenomenon were considered a priori: decreased
      hepatic uptake from blood to liver and decreased biliary excretion from liver to
      bile. The tissue uptake clearance (CLup) of octreotide in plasma and several
      tissues was determined, and extensive uptake of octreotide (0.20 ml/min/g liver)
      was observed only in liver. The kinetic analysis indicated that CLup in liver
      fell to 10% of controls after administration of both TCA and DBSP. To compare
      CLup between in vivo and in vitro, the initial velocity of octreotide uptake by
      isolated hepatocytes and primary cultured hepatocytes was measured. The estimated
      kinetic parameters KM and Vmax were approximately 100 microM and 200
      pmol/min/10(6) cells in both systems, respectively. Hepatic uptake clearance
      estimated from the in vitro data was comparable with that observed in vivo.
      Biliary excretion of octreotide is reduced in Eisai hyperbilirubinemic rats
      (EHBRs), which have a heredity defect of multispecific organic anion transporter
      on the bile canalicular membrane, compared with that of Sprague-Dawley rats. The
      kinetic analysis demonstrated that the hepatic uptake was reduced in EHBRs. The
      uptake study using primary cultured hepatocytes suggested that a high level of
      unidentified endogenous substrate(s) in EHBR plasma may be responsible for the
      reduction of hepatic uptake of octreotide in EHBRs. In conclusion, we have
      demonstrated in vivo that carrier-mediated hepatic uptake of octreotide is
      inhibited by TCA and DBSP and that the CLup obtained in vivo is comparable with
      the CLup obtained in vitro in isolated hepatocytes and primary cultured
      hepatocytes.

PMID- 9152592
TI  - Nonlinear pharmacokinetics of cyclophosphamide and 4
      hydroxycyclophosphamide/aldophosphamide in patients with metastatic breast cancer
      receiving high-dose chemotherapy followed by autologous bone marrow
      transplantation.
AB  - The pharmacokinetics of cyclophosphamide and 4
      hydroxycyclophosphamide/aldophosphamide has been evaluated in 12 patients with
      metastatic breast cancer undergoing high-dose chemotherapy followed by bone
      marrow transplantation. Each patient received an initial dose of 4 g/m2 of
      cyclophosphamide over 90 min to prime peripheral blood progenitor cells (the
      first course), and 3 weeks later, 6 g/m2 of cyclophosphamide with 800 mg/m2 of
      thiotepa by 96-hr infusion before marrow stem cell infusion (the second course).
      Whole blood cyclophosphamide and 4-hydroxycyclophosphamide/aldophosphamide
      concentrations were measured by a GC-EIMS method using deuterium labeled
      compounds as internal standards. In addition, plasma and urine cyclophosphamide
      concentrations were determined by a GC assay. Whole blood concentrations of
      cyclophosphamide and 4-hydroxycyclophosphamide/aldophosphamide vs. time data and
      urinary excretion of cyclophosphamide data from the first course were co-modeled
      using a one-compartment model with Michaelis-Menten saturable elimination in
      parallel with first-order renal elimination (N = 7) or first-order metabolic and
      renal elimination (N = 5) for cyclophosphamide and one-compartment model with
      first-order elimination for 4-hydroxycyclophosphamide/aldophosphamide. The
      parallelism between cyclophosphamide and 4
      hydroxycyclophosphamide/aldophosphamide disposition curves implies that the
      pharmacokinetics of 4-hydroxycyclophosphamide/aldophosphamide is formation
      limited; only the fractional 4-hydroxycyclophosphamide/ aldophosphamide clearance
      rate (Clmet/Fmet) can be estimated. The mean Vmax and Km for cyclophosphamide
      were 0.78 microM/min and 247 microM, respectively. The mean nonrenal clearance
      (Clnr) of cyclophosphamide for five patients with apparent first-order
      elimination of cyclophosphamide was 67 ml/min. The mean Clmet/Fmet of 4
      hydroxycyclophosphamide/aldophosphamide was 2982 ml/min. The mean renal clearance
      (Clr) of cyclophosphamide was 29 ml/min and 24 ml/min for the first course and
      the second course, respectively. The correlations between cyclophosphamide AUCs
      and 4-hydroxycyclophosphamide/aldophosphamide AUCs were sought for both drug
      courses. Blood and plasma cyclophosphamide concentrations were remarkably
      similar, indicating that cyclophosphamide partitions equally in the red cell and
      plasma volume. Computer simulation of the effect of potential alterations in
      Michaelis-Menten saturable elimination and renal clearance on 4
      hydroxycyclophosphamide/aldophosphamide has been used to illustrate the complex
      relationship between the exposure to parent compound and active metabolite.

PMID- 9152593
TI  - Kinetics of hepatic accumulation of dextrans in isolated perfused rat livers.
AB  - The role of various processes (uptake, release, metabolism, and excretion) in the
      hepatic accumulation of dextrans was investigated in isolated perfused rat livers
      (IPRLs). Single-pass IPRLs were infused with fluorescein-dextran (FD) with a
      molecular weight (MW) of 70,000 (FD-70) for 15, 30, 45, or 60 min, and inlet and
      outlet samples and livers were collected. In addition, two groups of livers were
      infused with FD-70 for 60 min, followed by 30 or 60 min of drug-free perfusion.
      The concentrations of the macromolecule in the samples were measured by a size
      exclusion chromatographic method. Similar, but limited, experiments were also
      conducted for FDs with MWs of 4,000 (FD-4) and 150,000 (FD-150). In addition, the
      metabolism of all three FDs were investigated using liver homogenates. Because of
      low hepatic extraction, the concentrations of dextrans in the inlet and outlet
      perfusates were almost the same during the entire perfusion. However, liver
      concentrations increased almost linearly during the infusion of FD-70 (0-60 min)
      and declined slowly thereafter (60-120 min). The apparent hepatic extraction
      ratio (Eapp) values, estimated directly from the concentrations of FDs in the
      liver, were MW dependent; Eapp of FD-4 (0.124% +/- 0.015%) was significantly (p <
      0.05) less than that for FD-70 (0.677% +/- 0.193%) or FD-150 (0.711% +/- 0.022%).
      The metabolism and biliary excretion of all FDs were negligible during the
      perfusion time. The mean residence time of FD-70 in the liver, estimated by
      nonlinear regression analysis of experimental data, was 248 min. These studies
      define the role of various processes involved in the slow (but substantial) and
      MW dependent hepatic accumulation of dextrans.

PMID- 9152594
TI  - Metabolism of phencyclidine by human liver microsomes.
AB  - These studies examined in vitro metabolism of phencyclidine (PCP) in a series of
      human liver microsomes (N = 10). Each sample was characterized for cytochrome
      P450 (CYP) content and for CYP1A, CYP2A, CYP2C, CYP2D, CYP2E, CYP3A, CYP4A, and
      lauric acid 11-hydroxylation metabolic activities. At least five PCP metabolites
      (c-PPC, t-PPC, PCHP, an unknown metabolite, and an irreversibly bound metabolite)
      were formed by the various human liver microsomes. Nevertheless, there was a
      large degree of inter-individual variation in the metabolite formation. For
      example, the irreversibly bound metabolite was formed in detectable amounts in
      only four of the ten samples. c-PPC, t-PPC and the irreversibly bound PCP
      metabolite formation rates significantly correlated with CYP3A activity. The
      CYP3A inhibitor troleandomycin was used to inhibit the formation of PCP
      metabolites. Troleandomycin inhibition was dose dependent with the highest dose
      producing complete inhibition of the formation of c-PPC, t-PPC, PCHP, and the
      irreversibly bound metabolite. In addition, PCP inhibited CYP3A-mediated
      testosterone 6 beta-hydroxylation by 50%. Furthermore, the relative intensity of
      CYP3A immunoreactive proteins significantly correlated with testosterone 6 beta
      hydroxylation and with PCP metabolite formation (except for the unknown
      metabolite). PCHP formation also correlated with CYP1A activity, while the
      formation of the unknown PCP metabolite correlated with CYP2A activity. These
      studies suggest that several CYP isoforms contribute to PCP metabolism and that
      CYP3A plays a major role in PCP biotransformation in human liver microsomes.

PMID- 9152595
TI  - Metabolism of the aryl hydrocarbon receptor agonist 3,3',4,4'-tetrachlorobiphenyl
      by the marine fish scup (Stenotomus chrysops) in vivo and in vitro.
AB  - The metabolism of the polychlorinated biphenyl congener 3,3',4,4'
      tetrachlorobiphenyl (TCB) was examined in vitro and in vivo in the marine fish
      scup (Stenotomus chrysops). Untreated scup liver microsomes catalyzed metabolism
      of TCB with an estimated KM of 0.7 microM, at a rate < or = 0.13 pmol/min/mg.
      Metabolism was NADPH-dependent and inhibited by cytochrome c and CO, indicating
      cytochrome P450 (CYP) involvement. alpha-Naphthoflavone strongly inhibited
      microsomal TCB metabolism, and treatment of fish with CYP1A inducers increased
      the rates by approximately 2-fold, suggesting involvement of CYP1A. Scup were
      injected intraperitoneally with 0.1 or 5 mg TCB/kg and sampled on days 1-16 after
      treatment (after 3 days without food at each sampling). Concentrations of
      unmetabolized TCB in liver peaked on day 5 in low dose fish and on day 12 in high
      dose fish. In both groups the TCB content in the liver had declined 60% or more
      by day 16, suggesting depuration or redistribution from the liver. GC and MS
      revealed TCB and TCB metabolites in bile within 24 hr of treatment. The
      concentrations of TCB and metabolites in bile peaked at the same time that TCB
      concentrations peaked in the liver. The major metabolites were 5-hydroxy-3,3'4,4'
      TCB (5-OH-TCB) and 4-hydroxy-3,3',5,4'-TCB (4-OH-TCB); 2-hydroxy-3,3',4,4'-TCB
      and 6-hydroxy-3,3',4,4'-TCB were minor metabolites. Animals given the high dose
      had much less 5-OH-TCB and much more parent TCB in bile than did fish given the
      low dose. Amounts of 4-OH-TCB in bile did not differ between doses. The reduced
      excretion of 5-OH-TCB coincided with a suppression of CYP1A in fish given the
      high dose, that did not occur in low dose fish, consistent with an involvement of
      CYP1A in TCB metabolism and particularly in formation of 5-OH-TCB. This study
      provides the first direct demonstration of 3,3',4,4'-TCB metabolism by fish. Data
      also indicate that these fish are able to eliminate TCB both as parent compound
      and as metabolites, despite a very slow rate of metabolism in vitro.

PMID- 9152596
TI  - Disposition and metabolism of olanzapine in mice, dogs, and rhesus monkeys.
AB  - Olanzapine (OLZ) is a novel antipsychotic agent with a high affinity for
      serotonin (5-HT2), dopamine (D1/D2/D4), muscarinic (m1-m5), adrenergic (alpha 1),
      and histamine (H1) receptors. The pharmacokinetics, excretion, and metabolism of
      OLZ were studied in CD-1 mice, beagle dogs, and rhesus monkeys after a single
      oral and/or intravenous dose of [14C]OLZ. After oral administration, OLZ was well
      absorbed in dogs (absolute bioavailability of 73%) and to the extent of at least
      55% in monkeys and 32% in mice. The terminal elimination half-life of OLZ was
      relatively short in mice and monkeys (approximately 3 hr) and long in dogs
      (approximately 9 hr). In mice and dogs, radioactivity was predominantly
      eliminated in feces; but, in monkeys, the major route of elimination of
      radioactivity was urine. Dogs and monkeys excreted in urine, respectively, 38%
      and 55% of the dose over a 168-hr period, whereas the fraction of the dose
      excreted in urine of mice over the collection period (120 hr) was 32%. OLZ was
      subject to substantial first-pass metabolism; at the tmax, OLZ accounted for 19%,
      18%, and 8% of the radioactivity, in mice, dogs, and monkeys, respectively. The
      ratio of AUC OLZ to AUC radioactivity was, respectively, 10%, 14%, and 4% in
      mice, dogs, and monkeys. The principal urinary metabolites in mice were 7-hydroxy
      OLZ glucuronide, 2-hydroxymethyl OLZ, and 2-carboxy OLZ accounting for
      approximately 10%, 4%, and 2% of the dose. Metabolites that were present in urine
      in lesser amounts were 7-hydroxy OLZ, N-desmethyl OLZ, and N-desmethyl-2
      hydroxymethyl OLZ. In dogs, the major metabolite accounting for approximately 8%
      of the dose was 7-hydroxy-N-oxide OLZ. Other metabolites identified were 2
      hydroxymethyl OLZ, 2-carboxy OLZ, N-oxide OLZ, 7-hydroxy OLZ, and its glucuronide
      and N-desmethyl OLZ. The major metabolite in monkey urine was N-desmethyl-2
      carboxy OLZ, and accounted for approximately 17% of the dose. In addition, N
      oxide-2-hydroxymethyl, 2-carboxyl OLZ, and 2-hydroxymethyl OLZ were identified in
      monkey urine. Thus, in mice and dogs, OLZ was metabolized through aromatic
      hydroxylation, allylic oxidation, N-dealkylation, and N-oxidation reactions. In
      monkeys, OLZ was biotransformed mainly through double oxidation reactions
      involving the allylic carbon and methyl piperazine nitrogen. Whereas the
      oxidative metabolic profile of OLZ in animals was similar to that of humans,
      animals were notable for not forming appreciable amounts of the principal human
      metabolite (i.e. 10-N-glucuronide OLZ).

PMID- 9152597
TI  - Effects of pantoprazole on xenobiotic metabolizing enzymes in rat liver
      microsomes: a comparison with other proton pump inhibitors.
AB  - The effects of pantoprazole on xenobiotic metabolizing enzymes in rat liver
      microsomes were examined. Groups of female Sprague-Dawley rats were orally
      administered pantoprazole and other proton pump inhibitors, omeprazole and
      lansoprazole, at 5, 50, or 300 mg/kg/day for 7 days, followed by assays to detect
      changes in the levels of liver microsomal protein, cytochrome P450, cytochrome
      b5, NADPH cytochrome c reductase, and drug metabolizing enzyme activities.
      Increases in total cytochrome P450 contents were evident after a 7-day high-dose
      administration of all the proton pump inhibitors tested, and the increase by
      treatment with pantoprazole was less than that with lansoprazole. The three
      proton pump inhibitors increased the enzymatic activities and cytochrome P450
      enzyme levels of CYP1A, CYP2B, and CYP3A. CYP1A was less induced with
      pantoprazole than with omeprazole or lansoprazole. In contrast, CYP2B was more
      strongly induced with pantoprazole than with other proton pump inhibitors. NADPH
      cytochrome c reductase was induced with omeprazole and pantoprazole. The present
      results suggest that enzyme induction differs among these proton pump inhibitors
      not only quantitatively but also qualitatively.

PMID- 9152598
TI  - Metabolic disposition of the cognition activator tacrine in rats, dogs, and
      humans. Species comparisons.
AB  - The metabolic fate of tacrine [1,2,3,4-tetrahydro-9-acridinamine
      monohydrochloride monohydrate (THA)] was examined in rats, dogs, and humans.
      After administration of single oral doses of [14C]THA to rats, dogs, and humans,
      drug-derived material was well absorbed, with urinary excretion being the
      predominant route of radiolabel elimination. Metabolic profiling of plasma and
      urine from rats, dogs, and humans showed THA to be extensively metabolized with
      marked species differences in quantitative amounts of metabolites observed.
      Plasma profiles were similar to respective urinary profiles in all three species.
      Present in profiles of urine from rats were 1-hydroxy (OH)-THA (major), 2-OH-THA,
      and 4-OHA-THA, and unchanged THA. Also observed were trace amounts of more polar
      metabolites, presumably arising from sequential metabolism. Metabolic profiling
      of dog urine also showed 1-OH-THA to be the major metabolite, with trace amounts
      of the 2-OHA-THA and 4-OH-THA regioisomers and THA excreted. In dog urine, more
      of the radioactivity was associated with polar metabolites, including 1,3
      dihydroxy-THA and a dihydrodiol metabolite. Human urinary metabolic profiles were
      more similar to that in dogs than in rats, with no single metabolite constituting
      > 10% of urinary radioactivity. Present in human urine were phenol glucuronide
      metabolites, of which 7-OH-THA was identified as an aglycone. Relevance of the
      marked quantitative differences in THA metabolism between rats, dogs, and humans
      to species differences in THA hepatotoxic potential remains to be established.

PMID- 9152599
TI  - Inhibition of human drug metabolizing cytochromes P450 by anastrozole, a potent
      and selective inhibitor of aromatase.
AB  - Anastrozole (2,2'[5(1H-1,2,4-triazol-1-ylmethyl)-1,3-phenylene]- bis(2
      methylproprionitrile)) is a potent third-generation inhibitor of aromatase,
      currently marketed as a treatment for postmenopausal women with advanced breast
      cancer. While its potency and selectivity for inhibition of estrogen synthesis
      has been established in both preclinical and clinical studies, this study used in
      vitro methods to examine the effects of anastrozole on several drug metabolizing
      CYP enzymes found in human liver. Human liver microsomes were co-incubated with
      anastrozole and probe substrates for CYP1A2 (phenacetin), CYP2A6 (coumarin),
      CYP2C9 (tolbutamide), CYP2D6 (dextromethorphan), and CYP3A (nifedipine). The
      formation of the CYP-specific metabolites following co-incubation with various
      anastrozole concentrations was determined to establish IC50 and Ki values for
      these enzymes. While anastrozole did not inhibit CYP2A6 and CYP2D6 activities at
      concentrations below 500 microM, this compound inhibited CYP1A2, CYP2C9, and
      CYP3A activities with Ki values of 8, 10, and 10 microM, respectively. Dixon
      plots used to determine the Ki values for the inhibition of CYP1A2 and CYP3A
      activities by anastrozole were biphasic, indicating additional lower affinity Ki
      values. Major metabolites of anastrozole did not retain the ability to inhibit
      the metabolism of nifedipine (CYP3A). The results of this study indicate that,
      although anastrozole can inhibit CYP1A2, 2C9, and 3A-mediated catalytic
      activities, this compound would not be expected to cause clinically significant
      interactions with other CYP-metabolized drugs at physiologically relevant
      concentrations achieved during therapy with Arimidex (Zeneca, Ltd., Macclesfield,
      UK) 1-mg.

PMID- 9152600
TI  - Biotransformation of clozapine in humans.
AB  - The metabolic pathways of clozapine (CZ, Clozaril (Novartis Pharmaceuticals
      Corporation, East Hanover, NJ), 8-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo
      [b,e][1,4]diazepine, a tricyclic benzodiazepine neuroleptic which has a reduced
      risk of unwanted neurological effects, were determined in normal male volunteers
      after a single oral dose of 50 mg of [14C]CZ. There was no radio-activity in
      exhaled breath, and excretion of total radioactivity was approximately 50% in
      urine and 30% in feces; parent CZ was a minor component in the excreta. The
      metabolic profiles were determined in urine and feces using HPLC coupled with
      radioactivity monitoring. The major metabolic pathways were demethylation,
      oxidation of the aromatic ring in the 7- and 8-positions, and conjugation. The
      major urinary components were 8-hydroxy-deschloro-DCZ (desmethylCZ) and its
      glucuronide, 7-hydroxy-8-chloro-DCZ sulfate and CZ-NO (clozapine N-oxide). Minor
      amounts of CZ, 7-hydroxy-8-chloro-CZ glucuronide and DCZ were also present. In
      feces the major component was CZ-N-glucuronide. Urinary excretion of CZ-NO was
      more rapid than the products of aromatic ring hydroxylation and conjugation.

PMID- 9152601
TI  - Effect of hematocrit and albumin concentration on hepatic clearance of tacrolimus
      (FK506) during rabbit liver perfusion.
AB  - Tacrolimus is an immunosuppressive agent used for organ transplantation. Studies
      were performed to examine the influence of different perfusate hematocrits and
      albumin concentrations on hepatic extraction of tacrolimus. In vitro binding,
      efflux and influx between red blood cells (RBCs) and buffer or plasma, and rabbit
      liver perfusion with use of human erythrocytes were studied. In the range of
      hematocrits from 0.05 to 0.4, plasma concentrations of tacrolimus were not
      affected by increased albumin content. Increased hematocrit caused decreases in
      whole blood:plasma (buffer) concentration ratios. The binding capacity of drug
      with RBCs was independent of hematocrit, with a value of 440 ng/ml of RBCs; the
      binding affinity was 0.876 ng/ml using plasma or buffer. Diffusion of tacrolimus
      from RBCs to buffer was rapid with a clearance of 0.940 ml/min, and equilibration
      was achieved within 2 min. Diffusion in the opposite direction (buffer-RBCs) was
      slower with a clearance of 0.576 ml/min. In such diffusion studies, plasma
      produced a greater difference between efflux (1.70 ml/min) and influx (0.276
      ml/min) clearances. During liver perfusion, the major factor regulating
      elimination of tacrolimus was hematocrit. Both well-stirred and parallel-tube
      models reflected a low extraction ratio drug with values of 0.15 and 0.17 for the
      0.05 and 0.2 hematocrits. Intrinsic clearances were 8.43 and 17.44 ml/min for the
      well-stirred and parallel-tube models. Albumin had a negligible influence on
      liver extraction of drug. A model-building process of characterizing nonlinear
      RBC binding, RBC diffusion rates, and liver perfusion parameters allows the
      complexities of tacrolimus hepatic clearance to be dissected and shows that
      strong RBC binding can be artificially perceived as causing a high clearance of
      the drug.

PMID- 9152602
TI  - Oxidation of xenobiotics by recombinant human cytochrome P450 1B1.
AB  - Human cytochrome P450 (P450) 1B1 (CYP1B1) has recently been shown to be an
      important enzyme in the activation of diverse procarcinogens such as arylarenes,
      nitroarenes, and arylamines to reactive metabolites that cause DNA damage in the
      cells. However, it is not known whether this P450 enzyme also plays roles in the
      oxidation of certain drugs or model substrates commonly used in P450 assays. We
      examined the substrate oxidation activities of recombinant human CYP1B1 in yeast
      microsomes and compared these activities with those catalyzed by reconstituted
      systems containing recombinant CYP1A1 and CYP1A2 which were isolated from
      membranes of Escherichia coli in which respective cDNAs have been expressed.
      Catalytic activities towards some of the model substrates of other human P450
      enzymes including CYP2A6, 2C9, 2C19, 2D6, 2E1, and 3A4 were also determined and
      compared. CYP1B1 catalyzed benzo[a]pyrene 3-hydroxylation at rates lower than
      those of CYP1A1 but higher than those of CYP1A2. The activity towards 7
      ethoxyresorufin O-deethylation catalyzed by CYP1B1 was about one-tenth of that of
      CYP1A1, but the Km values were lower for CYP1B1 than those for CYP1A1 and CYP1A2.
      CYP1B1 was also able to catalyze the oxidation of theophylline and caffeine, two
      prototypic substrates for CYP1A2. CYP1B1 did not oxidize other typical P450
      substrates such as coumarin, tolbutamide, S-mephenytoin, chlorzoxazone,
      nifedipine, and testosterone, while low rates of oxidation of bufuralol and 7
      ethoxycoumarin were found for CYP1B1. These results indicate that CYP1B1 has
      catalytic activities overlapping CYP1A1 and CYP1A2 with respect to the oxidation
      of drugs and model P450 substrates, although the relative catalytic roles in
      these three P450 enzymes differ depending upon the substrates examined. A
      distinct marker activity of CYP1B1 has not been identified.

PMID- 9152603
TI  - Oxidative metabolism of clarithromycin in the presence of human liver microsomes.
      Major role for the cytochrome P4503A (CYP3A) subfamily.
AB  - In vitro studies were conducted to identify the hepatic cytochrome P450 (CYP)
      protein(s) involved in the oxidative metabolism of [14C]clarithromycin (CLAR) in
      the presence of native human liver microsomes. The identity of the two major CLAR
      metabolites present in microsome incubates, 14-(R)-hydroxy-CLAR and N-desmethyl
      CLAR, was confirmed by MS. Over the CLAR concentration range of 1.0-140 microM,
      the rate of CLAR 14-(R)-hydroxylation (KM = 48 +/- 17.7 microM; Vmax = 206 +/- 76
      pmol/min/mg protein; Vmax/KM = 4.2 +/- 0.21 microliters/min/mg; mean +/- SD, N =
      3 livers) and N-demethylation (KM = 59.1 +/- 24.0 microM; Vmax = 189 +/- 52.0
      pmol/min/mg protein; Vmax/KM = 3.3 +/- 0.53 microliters/min/mg) conformed to
      monophasic (saturable) Michaelis-Menten kinetics and was highly correlated (r =
      0.90-0.92; p < 0.001; N = 11) with CYP3A-selective erythromycin N-demethylase
      activity. Ketoconazole (< or = 2.0 microM) or troleadomycin, CYP3A-selective
      inhibitors, markedly decreased (> or = 99%) the formation of both metabolites,
      whereas inhibitors selective of other CYP forms were relatively ineffective (< or
      = 10% inhibition). In agreement with chemical inhibitor studies, CLAR metabolism
      was only detectable with human B-lymphoblastoid microsomes containing cDNA
      expressed CYP3A4 (vs. CYP2C19, CYP2C9, CYP2D6, CYP1A2, CYP2E1, or CYP2A6).
      Furthermore, the apparent KM characterizing the 14-(R)-hydroxylation and N
      demethylation of CLAR in the presence of insect cell microsomes containing cDNA
      expressed CYP3A4 (KM = 18-63 microM) was similar to that obtained with native
      human liver microsomes. Based on the results of this study, it is concluded that
      the 14-(R)-hydroxylation and N-demethylation of CLAR is primarily mediated by one
      or more members of the human liver CYP3A subfamily.

PMID- 9152604
TI  - Biodistribution and pharmacokinetics of 131I-labeled LEX 032, a recombinant
      hybrid of antichymotrypsin.
AB  - Pharmacokinetic and biodistribution studies were conducted in rats on a novel
      serine protease inhibitor, LEX 032, that was radiolabeled with 131I by the Bolton
      Hunter reagent. LEX 032, a genetically engineered recombinant human
      nonglycosylated serpin, has been shown to have antiinflammatory properties in a
      number of animal models of inflammation and reperfusion injury. When 131I-LEX 032
      was injected intravenously, a rapid whole body clearance of radioactivity was
      seen. Blood clearance followed a similar pattern. Forty-eight hours
      postinjection, 2.00 +/- 0.65 of the administered dose remained in the body.
      Greater than 59% of the radio-activity was excreted in the urine within the first
      24 hr. Little radioactivity was found in the feces. With the exception of the
      thyroid, no significant organ-related uptake was noted. Radioactivity in the
      liver peaked at 20 min postinjection, with 1.00 +/- 0.13% administered dose/g and
      approximately 10% administered dose in the whole liver. At 1 hr, uptake in the
      kidney (9.30 +/- 1.52% administered dose/g) was the highest among all tissues,
      except for the thyroid. Gamma camera images were consistent with the
      biodistribution pattern. Pharmacokinetics and biodistribution were not affected
      by the dose of LEX 032 and were quite different from those of glycosylated wild
      type antichymotrypsin. These data indicate that LEX 032 exhibits the
      pharmacokinetics expected of a nonglycosylated 45 kDa protein.

PMID- 9152605
TI  - In vitro metabolism of three major isomers of retinoic acid in rats. Intersex and
      interstrain comparison.
AB  - Cytochrome P450 expression in liver is influenced by several factors, including
      sex and strain. Whereas little is known about their metabolic capabilities,
      Hairless rats are widely used for the studies of tropical agents. We compared
      Sprague-Dawley and Hairless rat metabolic behavior to validate the use of
      Hairless rats in pharmacokinetic and metabolic studies of topically applied
      drugs. Liver microsomes of male and female rats of both strains were used to
      investigate the in vitro metabolism of three retinoic acid (RA) isomers: all
      trans-RA, 13-cis-RA, and 9-cis-RA. In all cases, a major isomerization of the
      tested isomer in the two others was observed. This process was independent of the
      presence of NADPH, but depended on the presence of microsomal proteins. In
      addition, we observed, to a lesser extent, the formation of 4-oxo metabolites (4
      oxo-all-trans-RA, 4-oxo-13-cis-RA, and 4-oxo-9-cis-RA), with the rate of
      formation of each of these compounds varying with the nature of the isomer
      incubated. The 4-oxo metabolites formed were statistically greater in male than
      in female rats in the two strains studied. No significant difference in RA
      biotransformation was observed between Sprague-Dawley and Hairless rats. In
      addition, no major difference was observed between the two strains concerning the
      expression of the different cytochrome P450 isoforms studied. In conclusion,
      phase I metabolism of RAs characterized by C4-hydroxylation varied with sex, but
      not within the two strains studied in rats. These results strengthen the
      relevance of the use of Hairless rats in pharmacokinetic and metabolic studies of
      topical agents, including retinoids.

PMID- 9152606
TI  - Effect of alcohol coadministration on the plasma and brain concentrations of
      cocaine in rats.
AB  - We investigated the effect of intravenous alcohol coadministration on the
      pharmacokinetics of cocaine in awake, freely moving rats using the microdialysis
      technique. Alcohol coadministration resulted in faster rate of cocaine absorption
      after intraperitoneal administration leading to higher cocaine plasma
      concentration. The higher plasma cocaine concentration resulted in a proportional
      increase in the cocaine brain extracellular fluid concentration. However, cocaine
      brain extracellular fluid/plasma distribution ratio, determined from the ratio of
      the corresponding cocaine area under the concentration-time curves, was not
      affected by alcohol coadministration. Cocaethylene was detected only after
      administration of cocaine + alcohol. The brain extracellular fluid/plasma
      distribution ratio of cocaethylene was similar to that of cocaine. The higher
      cocaine concentrations in plasma and brain extracellular fluid, in addition to
      the formation of the pharmacologically active metabolite cocaethylene are, at
      least partially, responsible for the increased cocaine effects produced after
      administration of this drug combination.

PMID- 9152607
TI  - The in vitro interaction of dexmedetomidine with human liver microsomal
      cytochrome P4502D6 (CYP2D6).
AB  - The effect of dexmedetomidine DEX on cytochrome P4502D6 (CYP2D6)-dependent
      dextromethorphan O-demethylase (DEXTROase) activity was studied using native
      human liver microsomes. DEX (0.01-4.0 microM inhibited DEXTROase activity (IC50 =
      1.8 +/- 0.25 microM; mean +/- SD; N = 5 livers) and was less potent than
      quinidine (QND), prototypical and clinically relevant CYP2D6 inhibitor (IC50 =
      0.22 +/- 0.02 microM; mean Ki = 0.07 microM). Similar results were obtained with
      human B-lymphoblast microsomes containing cDNA-expressed CYP2D6 (DEX, IC50 = 2.2
      microM; QND, IC50 0.15 microM). Formal kinetic analyses indicated that DEX was a
      reversible mixed (competitive/noncompetitive) inhibitor of DEXTROase activity in
      human liver microsomes, where Kies > Ki and alpha > 1 (Ki = 0.4 +/- 0.2 microM;
      Kies = 2.3 +/- 0.9 microM; alpha = 8.1 +/- 6.8; N = 3 livers). In addition, DEX
      elicited a Type IIb difference spectrum (lambda max approximately 436 nm; lambda
      min approximately 414 nm) when added to cDNA-expressed CYP2D6 under aerobic
      (oxidized) conditions. These data indicated that DEX was able to bind reversibly
      to the heme (ferric) iron of CYP2D6. It is postulated that binding occurs via the
      4(5)-substituted imidazole moiety. In this instance, binding was characterized by
      a spectral dissociation constant (Ks) of 0.4 microM that was identical to the Ki
      obtained with native human liver microsomes.

PMID- 9152608
TI  - Lethal drug interactions of sorivudine, a new antiviral drug, with oral 5
      fluorouracil prodrugs.
AB  - Rats were orally co-administered sorivudine (SRV: 1-beta-D-arabinofuranosyl-(E)-5
      (2-bromovinyl)uracil), a new oral antiviral drug for herpes zoster, with the oral
      anticancer drug tegafur (FT: 1-(2-tetrahydrofuryl)-5-fluorouracil as a prodrug of
      5-fluorouracil (5-FU) once daily to investigate a toxicokinetic mechanism of 15
      Japanese patients' deaths recently caused within a brief period by the drug
      interaction of these drugs. All the rats showed extremely elevated levels of 5-FU
      in plasma and tissues, including bone marrow and small intestine, and died within
      10 days, whereas the animals given the same dose of SRV or FT alone were still
      alive over 20 days without any appreciable toxic symptom. Before their death,
      there was marked damage of bone marrow, marked atrophy of intestinal membrane
      mucosa, marked decreases in white blood cells and platelets, diarrhea with bloody
      flux, and severe anorexia as reported with the Japanese patients. Data obtained
      by in vivo and in vitro studies strongly suggested that (E)-5-(2
      bromovinyl)uracil generated from SRV by gut flora was reduced in the presense of
      NADPH to a reactive form by hepatic dihydropyrimidine dehydrogenase (DPD), a key
      enzyme determining the tissue 5-FU levels, bound covalently to DPD as a suicide
      inhibitor, and markedly retarded the catabolism of 5-FU.

PMID- 9152609
TI  - Lymphocytic adenohypophysitis and lymphocytic infundibuloneurohypophysitis.
AB  - One hundred and twenty-four cases of lymphocytic adenohypophysitis have been
      reported since 1962. Nearly 60% of the cases in women involved inset of the
      disease in relation to pregnancy. Headache and visual field defects were the most
      frequent symptoms. Most patients showed signs of either isolated or multiple
      anterior pituitary hormone deficiency. ACTH secretion was impaired the most
      frequently, followed by TSH, gonadotropins, GH and PRL secretion. One third of
      the cases involved hyperprolactinemia. Tissue from patients with lymphocytic
      infundibuloneurohypophysitis, also suffering from DI, revealed lymphocytic
      inflammation limited to the infundibulum, stalk, and neurohypophysis. Twenty of
      these 124 lymphocytic adenohypophysitis patients developed DI before treatment,
      and neuroimaging studies revealed thickening of the pituitary stalk in some. At
      least in a few cases, chronic lymphocytic infiltration occurred in both the
      infundibuloneurohypophysitis and adenohypophysis. Although both lymphocytic
      adenohypophysitis and infundibuloneurohypophysitis may be caused by autoimmune
      disorders, the antigens involved may differ.

PMID- 9152610
TI  - Prolactin expresses differential effects on apoptotic cell death of luteal cells
      in vivo and in vitro.
AB  - PRL surges in female rats have dual effects of luteal function: either inducing
      luteolysis during the estrous cycle or rescuing and maintaining luteal function
      during pseudopregnancy. We analyzed these apparent contradictory effects in
      relation to apoptosis. The detection of fragmented DNA and in situ 3'-end
      labeling studies were done on corpora lutea (CL) collected from cycling rats at
      proestrus 1800 h (P1800 specimen) or pseudopregnant rats on day 6 (psp 6).
      Distinct DNA ladders were observed in P1800 samples as we previously reported,
      but only slight ones were found in psp 6 specimen. The effect of PRL on the
      induction of apoptosis was evaluated in vitro with dispersed luteal tissue. CL
      from cycling rats were exempted from a PRL surge by pre-treating donors with a
      dopamine agonist. The extent of apoptotic reaction in P1800 specimen depended on
      the doses of PRL added to the culture medium. In psp 6 specimen, in contrast, PRL
      suppressed the apoptotic reaction, increased the cell survival rate (MTT assay),
      and decreased the cell death rate (LDH assay). Furthermore, PRL enhanced 20 alpha
      hydroxysteroid dehydrogenase activity in P1800 specimen but suppressed it in psp
      6 specimen. In summary, PRL in rats is either an apoptosis-inducer or 
      suppressor, depending on the functional state of luteal cells.

PMID- 9152611
TI  - Histopathologic study of the pancreas shows a characteristic lymphocytic
      infiltration in Japanese patients with IDDM.
AB  - We examined at autopsy 47 cases (22 males and 25 females) of insulin-dependent
      diabetes mellitus (IDDM) from 21 hospitals in Japan to clarify the pathological
      changes that occur in the pancreas vs. those in control patients. The mean age
      was 39.7 +/- 13.9 (mean +/- SD) years, and the duration of IDDM from clinical
      onset was 13.1 +/- 6.5 years. Causes of death included renal complications,
      infections, acute diabetic complications such as ketoacidosis or hyper- or
      hypoglycemic coma, and atherosclerotic disease. This study revealed noticeable
      decreases in the islet area and beta cell area, and a slight decreases in the
      alpha cell area and preservation of the number of islets. Insulitis was found in
      only 1 case, representing 25% of the cases with a duration of IDDM of one year or
      less. Lymphocytic infiltration of the exocrine gland was seen in 22 cases
      (46.8%). Predominant phenotypes of the lymphocytes were T lymphocytes and
      macrophages. Fibrosis, fatty change and atrophy were also found. Although this is
      not a strictly age- and sex-matched study, the high incidence of lymphocytic
      infiltration of the exocrine pancreas indicates that the exocrine tissue as well
      as beta cells is the target of immune reactions in Japanese patients with IDDM.

PMID- 9152612
TI  - Quantitative RT-PCR for inhibin/activin subunits: measurements of rat
      hypothalamic and ovarian inhibin/activin subunit mRNAs during the estrous cycle.
AB  - Inhibins (alpha-beta(A) and alpha-beta(B)) and activins (beta(A)-beta(A), beta(A)
      beta(B) and beta(B)-beta(B)) were originally isolated from ovarian follicular
      fluids as FSH secretion modifiers. Inhibin/activin subunits, alpha, beta(A) and
      beta(B), are widely distributed in several tissues, including gonads and brain,
      and inhibins and activins have been reported to be involved in ovarian or
      hypothalamic functions. In this study, we established and employed a competitive
      RT-PCR assay system for rat inhibin/activin subunits by capillary electrophoresis
      to determine rat hypothalamic and ovarian inhibin/activin subunit mRNA levels
      during the estrous cycle. Linearity of standards for alpha, beta(A), and beta(B)
      subunit assays were between 0.01-0.3 amol, 0.003-0.09 amol and 0.002-0.02 amol of
      each fragment DNA as a standard, respectively. Hypothalamic beta(A) subunit mRNA
      during the estrous morning (1000 h) tended to be increased compared with that of
      the proestrous evening (1700 h), although they were not significantly different.
      Ovarian alpha subunit mRNA levels tended to be increased during the proestrous
      morning (1000 h) and were significantly increased in the proestrous evening (1700
      h), compared with diestrus and estrus (P < 0.05). Ovarian beta(A) subunit mRNA
      was also significantly higher in the proestrous evening, compared with diestrus
      and estrus (P < 0.05), but in the case of beta(B) subunit mRNA there was no
      difference among diestrus, proestrus and estrus. We thus established a sensitive
      competitive RT-PCR system for the measurement of inhibin/activin alpha, beta(A)
      and beta(B) subunits, and this assay system would be helpful for the study of
      inhibin/activin action in brain and other tissues where these factors are
      expressed at low levels.

PMID- 9152613
TI  - Glutamic acid decarboxylase65 (GAD65) antibodies and insulin auto-antibodies in
      Japanese patients with non-insulin-dependent diabetes mellitus.
AB  - To clarify whether glutamic acid decarboxylase65 antibodies (GAD65 Ab) and
      insulin autoantibodies (IAA) are good predictive markers for insulin-dependency
      in NIDDM, we studied GAD65 Ab and IAA in NIDDM patients treated with diet alone
      or in combination with oral hypoglycemic agents. GAD65 Ab were found in 12 or 29
      (5.2%, P = 0.079 vs. control) NIDDM patients and IAA in 8 of 229 (3.5%). The
      frequency of GAD65 Ab and IAA positivity in NIDDM did not differ significantly
      from those of healthy controls (2/150, 1.3%, 2/150, 1.3%, respectively), but the
      frequency of patients who were positive for either GAD65 Ab or IAA, or both, was
      significantly higher than that of normal controls (17/229, 7.4% and 4/150, 2.7%,
      respectively, P < 0.05). In addition, the prevalences of GAD65 Ab and of IAA in
      those patients whose disease durations, since the diagnosis of diabetes, were
      less than one year were significantly higher than those of controls (4/30, 13.3%,
      P < 0.05, 4/30, 13.3%, P < 0.05, respectively). We found no differences between
      GAD65 Ab positive- and negative-patients in either BMI or serum C-peptide levels.
      Over a one to five year follow-up period (mean 2.0 yrs), serum C-peptide levels
      gradually decreased necessitating insulin treatment in three of the patients
      positive for GAD65 Ab and/or IAA (3/17, 17.6%; two were positive for both GAD65
      Ab and IAA and one was positive for GAD65 Ab only). In contrast, only five
      patients negative for the two antibodies developed insulin requirement (5/212,
      2.4%, P < 0.01). These results suggest that GAD65 Ab and IAA are good markers for
      predicting the development of insulin dependency in NIDDM patients and that the
      predictive value for insulin-dependency in NIDDM is enhanced by measuring both
      antibodies.

PMID- 9152614
TI  - The regulation of the prolactin receptor gene expression in the mammary gland of
      early pregnant mouse.
AB  - The purpose of this research was to examine the hormonal regulation of the PRL
      receptor (PRL-R) gene expression in the mammary gland of early pregnant mouse.
      Following reverse-transcription, the quantity of PRL-R mRNA was determined by the
      competitive polymerase chain reaction. The level of long form PRL-R (PRL-RL) mRNA
      changed cyclically with the highest at estrus and the lowest at diestrus II. PRL
      RL mRNA was maintained at high levels for the first 3 days of pregnancy but
      declined to lower levels on day 5. Mice ovariectomized on day 2 of pregnancy
      maintained the same level of PRL-RL mRNA during the 24 h-period. The level of PRL
      R mRNA increased more than 2- and 2.7-fold with 17 beta-estradiol and PRL,
      respectively, and the progesterone concentration decreased its levels to 71% of
      the vehicle-injected control. The increasing action with 17 beta-estradiol and
      PRL was suppressed by administration of progesterone. Mice ovariectomized on day
      3 had a 1.8-fold higher level than that of the sham-operated control. The short
      form of PRL-R remained at low levels throughout the experiments. The results
      suggested that the expression of the PRL-R gene was suppressed when serum
      progesterone increased during early pregnancy.

PMID- 9152615
TI  - beta-Sitosterolemia with generalized eruptive xanthomatosis.
AB  - The clinical features of the first case of a patient with sitosterolemia and
      generalized eruptive xanthomatosis are described. A six-year-old girl with
      generalized eruption was referred to the lipid clinic because of the high plasma
      cholesterol levels determined by the enzymatic method. Neither clinical signs nor
      results of laboratory examinations appeared to be abnormal, except for the
      eruption and the increase in the plasma cholesterol concentration. A family
      survey revealed high plasma cholesterol concentrations in the mother and one of
      two other siblings. Histological examination showed the eruption to be a
      xanthoma. Plasma sterol analysis by high-performance liquid chromatography
      revealed a noticeable increase in plasma plant sterol as well as cholestanol
      concentrations in the proband and the hypercholesterolemic sibling. The other
      family members had slightly high plasma sterol concentrations. This is the first
      case of a sitosterolemic patient with eruptive xanthomatosis. The case indicates
      that the clinical features of the xanthoma in sitosterolemia are not only
      tuberous or tendon but also eruptive, and also suggests that sitosterolemia
      should be considered in the differential diagnosis of hypercholesterolemia in
      almost every case with tuberous or eruptive xanthoma. The diagnosis is clinically
      important, since the disease can be treated successfully by diet therapy and bile
      acid binding resins.

PMID- 9152616
TI  - ACTH-independent macronodular adrenocortical hyperplasia (AIMAH): report of two
      cases and the analysis of steroidogenic activity in adrenal nodules.
AB  - We report clinical findings and steroidogenic activities in adrenal tissues in 2
      cases of AIMAH. Endocrine studies revealed an undetectable level of plasma ACTH
      and a diminished circadian rhythm of plasma cortisol. A significant increase in
      plasma cortisol levels in response to ACTH stimulation was observed in both
      cases. After the administration of metyrapone in one case, urinary excretion of
      17-hydroxycorticosteroid (17-OHCS) significantly increased, although the plasma
      ACTH level did not respond. Computed tomography showed large masses in both
      adrenal glands, and bilateral uptake was identified on adrenal scintigraphy. The
      totals for the bilateral adrenal glands were 98 g and 105 g, respectively, and
      the left adrenal was larger than the right in both cases. Steroid content in the
      nodules measured by high performance liquid chromatography (HPLC) showed that the
      cortisol content was definitely lower than that in cortisol-producing adenoma
      (CPA) and even in normal adrenals. The activities of cytochrome P450c17, P450c21
      and P450c11 were evaluated in one case, and all of them were reduced in the
      nodules. Especially that of P450c17 was remarkably reduced. These data suggest
      that cortisol production in AIMAH is inefficient, and that the cause of Cushing's
      syndrome may be related to the marked increase in the number of cells or bulk of
      the tumor.

PMID- 9152617
TI  - Effects of noradrenaline on GnRH-secreting immortalized hypothalamic (GT1-7)
      neurons.
AB  - Noradrenaline (NA) is one of the most important neurotransmitters involved in the
      regulation of gonadotropin-releasing hormone (GnRH) secretion. In this study, the
      effects of NA on GnRH secretion, intracellular Ca2+ concentrations ([Ca2+]i), and
      membrane potentials were investigated in immortalized hypothalamic neurons (GT1
      7) to determine the direct effects of NA on GnRH cells. Cells were perfused in a
      plastic minicolumn, and GnRH concentrations of the effluents were measured. NA
      increased the release of GnRH in a dose-dependent manner. Cells were loaded with
      a 4 microM Fura 2-AM, and the ratio of the intensities of fluorescent emission at
      510 nm with excitation at 340 and 380 nm was calculated at 100-ms intervals. NA
      increased the [Ca2+]i responses of single GnRH cells dose-dependently. The NA
      induced [Ca2+]i increase was attenuated in the absence of extracellular calcium
      and was blocked by the beta-adrenergic antagonist propranolol, but not by the
      alpha-adrenergic antagonist phentolamine. The cell membrane potential was
      recorded with a whole-cell patch clamp amplifier with glass-electrodes. NA
      induced membrane depolarization under current-clamp conditions. The
      depolarization was also inhibited by propranolol, but not by phentolamine. The
      results show that NA directly affects the membrane potential of GT1-7 cells via
      beta-adrenergic receptors and induces Ca2+ mobilization; these effects stimulate
      GnRH secretion.

PMID- 9152618
TI  - Expression of LH-alpha and -beta subunit mRNAs in the rat placenta.
AB  - Gonadotropic activity is present in the placenta of various mammals including
      humans. Human and equine chorionic gonadotropin (CG) are well characterized and
      known to be glycoprotein hormones, as are pituitary LH, TSH and FSH. In the rat,
      however, the placental gonadotropin molecule has not been identified, and in fact
      the existence of CG in the rodent is still controversial. In the present study,
      the placental expression of mRNA for CG-like molecules was investigated by PCR
      with mixed primers designed for the CG-beta subunit based on the amino acid
      sequences common to the rat LH-beta, human LH-beta, equine LH-beta and human CG
      beta subunits and for the alpha subunit designed from the rat LH-alpha subunit.
      PCR with mRNA extracted from the placenta (day 10 of pregnancy) amplified several
      bands including cDNA identical to part of rat LH-alpha and -beta. Furthermore,
      expression of these genes was confirmed in the placenta on days 10, 12, 14, 16,
      18 and 20 of pregnancy by PCR with another set of primers specific to rat LH
      alpha and -beta and by Southern hybridization with 32P-labeled cDNAs for LH-alpha
      and -beta. The specific bands for these subunit mRNAs were amplified in the
      placenta, as well as in the positive control i.e. the anterior pituitary gland,
      but were not detected in other tissues including decidual tissue, liver, spleen,
      intestine, brain and kidney. Expression of the mRNAs was observed in both the
      junctional and labyrinth zones of the placental tissue. The rat choriocarcinoma
      cell line Rcho-1 also expressed LH-alpha but not LH-beta regardless of the stage
      of differentiation in vitro. Here we show the expression of LH-alpha and -beta
      mRNAs in the rat placenta.

PMID- 9152619
TI  - Incidence of hyperprolactinemia in patients with Hashimoto's thyroiditis.
AB  - The causes of hyperprolactinemia, the correlation between serum levels of PRL and
      thyroid function and magnetic resonance imaging (MRI) of the pituitary were
      studied in patients with chronic thyroiditis. Seventy-four female patients and 15
      normal control women participated in this clinical survey. Fourteen of 74
      patients with various thyroid conditions had increased serum PRL. The incidence
      of hyperprolactinemia in the overt primary hypothyroid group was 42.4% and was
      significantly higher than in any other group with normal serum thyroxine. There
      was a close association between the increment in serum PRL and of free
      triiodothyronine above the basal level after TRH administration. There were 14
      patients with hyperprolactinemia in three of which serum PRL was over 60
      micrograms/L. PRL producing tumor, severe primary hypothyroidism and liver
      cirrhosis were detected in these three patients, respectively. These results
      indicate that the pathogenesis of increased serum PRL was not uniform in patients
      with Hashimoto's thyroiditis, although there was a correlation between
      hyperprolactinemia and impaired thyroid function. It is proposed, therefore, to
      measure and follow serum levels of PRL and MRI of the pituitary in patients with
      chronic thyroiditis, especially with impaired thyroid function.

PMID- 9152620
TI  - Gonadal dysgenesis: associations between clinical features and sex of rearing.
AB  - The purpose of this study was to review the phenotypic and endocrine features or
      a series of patients with ambiguous genitalia or sex-reversal due to gonadal
      dysgenesis (GD) and to analyse the impact of these on the decision about sex of
      rearing. This study is a retrospective analysis of 22 patients with GD treated
      between 1964 and 1994. We assessed external genitalia, internal genitalia,
      internal genital structures, gonadal morphology (n = 22), basal and human CG
      (hCG) stimulated serum testosterone levels (n = 11) and serum gonadotropin levels
      (n = 13) in patients with GD. Basal and hCG stimulated testosterone levels were
      also measured for 43 control patients. There were no significant associations or
      correlations between internal or external genital phenotype, endocrine function
      and gonadal morphology. There was a significant association between sex of
      rearing and external genitalia (P = 0.03). Patients with gonadal dysgenesis had
      significantly lower stimulated/basal testosterone levels than the controls (P =
      0.0001). Given that the clinical features of various forms of GD overlap
      considerably, gonadal biopsy should remain the investigation of choice when
      attempting to define the pathology.

PMID- 9152621
TI  - A case of primary hyperparathyroidism accompanying multiple myeloma.
AB  - We report a case of 77-year-old woman who presented with lumbago and
      hypercalcemia. Multiple myeloma (MM) was first diagnosed by serum protein
      electrophoresis and bone marrow aspiration, but intact parathyroid hormone
      (intactPTH) was also found to be high in the presence of persistent hypercalcemia
      with anorexia and nausea. After lowering serum calcium with bisphosphonate
      administration, parathyroidectomy was performed. Upon histologic examination, the
      tumor was determined to be parathyroidal chief-cell hyperplasia and the patient
      was treated with melphalan and prednisolone. The relationship between MM and
      primary hyperparathyroidism (I degree HPT) remains unknown. Although the co
      existence of MM and I degree HPT was reported in 12 reports from various parts of
      the world, there was only 1 report in Japan. The present case is an example of
      successful treatment for a complicated disorder, and suggests that patients
      suffering from bone pain or hypercalcemia need to be examined both
      endocrinologically and hematologically.

PMID- 9152622
TI  - Comparative concentrations of growth hormone-binding protein in maternal
      circulation, fetal circulation, and amniotic fluid.
AB  - Fetal growth is thought to be independent of the concentration of GH, although
      circulating levels of GH are high in the human fetus. To elucidate the role of GH
      in fetal development, levels of GH-binding protein (GHBP) were measured in the
      serum of nonpregnant and pregnant women and neonates as well as in amniotic fluid
      obtained at various stages of gestation. Total GHBP (the sum of free GHBP and
      GHBP bound to GH) is measured by a ligand-mediated immunofunctional assay. GHBP
      concentrations in adult serum were not changed by pregnancy or the stage of
      gestation. A significant correlation was observed between the concentration of
      GHBP in the umbilical artery and vein. No correlations were observed between the
      GHBP concentration and such measures of fetal growth as fetal weight and fetal
      age. Although the neonatal concentrations of GHBP were significantly lower than
      those of pregnant women, no correlation was observed between them. GHBP was also
      present in the amniotic fluid from early to late gestation at concentrations
      higher than in the cord serum of the neonate. The amniotic GHBP concentration in
      late gestation was significantly higher than in early gestation. GHBP appears to
      be derived from GH receptors of fetal organs (most probably fetal liver). The low
      level of GHBP in fetal serum may be the result of a decrease in GH receptors
      caused by high levels of circulating GH. GHBP levels in amniotic fluids may be
      related to the development or maturation of the fetus.

PMID- 9152623
TI  - A case of active acromegalic woman with a marked increase in serum insulin-like
      growth factor-1 levels after delivery.
AB  - Pregnancy in a woman with active acromegaly is very rare, because amenorrhea, due
      to hyperprolactinemia and disturbed pituitary gonadotropin secretion may cause
      infertility. We report a 28-year-old pregnant woman with untreated acromegaly,
      who was followed up from early pregnancy to delivery. Her pregnancy was
      uneventful, and she went into spontaneous labor at 38 weeks and delivered a
      normal infant. Her serum GH levels were further increased in late pregnancy,
      followed by decreased in postpartum periods, which may be associated with
      enlargement of pituitary adenoma during pregnancy. In contrast with serum GH, her
      serum insulin-like growth factor-1 (IGF-1) levels were dissociated with her serum
      GH levels during late pregnant and postpartum period. Her serum GH and IGF-1
      levels in late pregnancy were different from the levels in pregnant women with
      acromegaly reported previously.

PMID- 9152624
TI  - A case of adrenal insufficiency due to acquired hypothalamic CRH deficiency.
AB  - A 40-year-old woman with adrenal insufficiency was clinically diagnosed and
      examined with human corticotropin releasing hormone (CRH). This patient with
      secondary hypo-adrenalism has shown a normal serum cortisol response to exogenous
      ACTH administration and has been examined with CRH, lysine-vasopressin (LVP) and
      insulin tolerance test (ITT), respectively. Success in secreting ACTH in response
      to both CRH and LVP tests, but not ITT, suggests that this disorder was possibly
      due to a hypothalamic CRH deficiency rather than pituitary corticotroph
      dysfunction. A combination of the CRH test and ITT has come to play an
      increasingly significant role in the diagnosis and differential diagnosis of
      isolated ACTH deficiency syndrome.

PMID- 9152625
TI  - Effects of chlormadinone acetate and ethinylestradiol treatment on epididymal 5
      alpha-reductase activities in patients with prostate cancer.
AB  - The difference between in vivo and in vitro inhibitory effects on epididymal 5
      alpha-reductase was investigated by using epididymides obtained from patients
      treated with chlormadinone acetate (6-chloro-3,20-dioxo-4,6-pregnadien-17-yl
      acetate, CMA) or ethinylestradiol (17 alpha-ethynyl-1,3,5(10)-estratriene-3,17
      beta-diol, EE2). In the in vitro study CMA exhibited competitive inhibition,
      whereas EE2 was a noncompetitive inhibitor of human epididymal 5 alpha-reductase.
      Their in vitro inhibitory effects were weak compared with the effect of
      finasteride ((-)-N-tert-butyl-3-oxo-4-aza-5 alpha-androst-1-ene-17 beta
      carboxamide), a steroidal 5 alpha-reductase inhibitor. The Ki values of CMA, EE2,
      and finasteride were 1.4 x 10(-5) M, 1.5 x 10(-5) M, and 1.3 x 10(-9) M,
      respectively. Despite their weak in vitro inhibitory potency, CMA and EE2
      strongly inhibited testosterone 5 alpha-reductase in vivo. There were regional
      differences in inhibitions by CMA and EE2 on human epididymal 5 alpha-reductase
      activity depending on the site of the epididymis; the efferent ductules, the
      head, the body or the tail. In vivo administration of CMA reduced epididymal 5
      alpha-reductase activity by 49.7% to 89.4%. In vivo administration of EE2 reduced
      epididymal 5 alpha-reductase activity by 82.7% to 96.3%. The apparent Km values
      for the enzyme in patients treated with CMA or EE2 and untreated patients did not
      differ significantly. The Vmax values were significantly decreased in treated
      patients. These findings suggest that the marked in vivo inhibition of 5 alpha
      reductase induced by CMA and EE2 was not related to the direct action of these
      compounds, but resulted from a reduction in the amount of the enzyme.

PMID- 9152626
TI  - Inhibition of GH releasing factor (GRF)-induced GH secretion by intraruminal
      infusion of volatile fatty acids (VFA) in sheep.
AB  - A VFA mixture solution containing acetate, propionate and butyrate (the molar
      ratio of acetate, propionate and n-butyrate = 61.7:24.3:14.0) was infused into
      the rumen at various rates (53.5, 107 and 214 mumol kg-1 min-1) over 6 h to
      examine the effects on basal and growth hormone-releasing factor (GRF, 0.25
      micrograms kg-1)-induced increase in secretion of GH, insulin, glucagon and
      somatostatin (SRIF) in five castrated male sheep. Intraruminal infusion of the
      VFA mixture into the 18-h-fasted animals at the rates of 53.5, 107 and 214 mumol
      kg-1 min-1 finally raised the total intraruminal VFA concentration from 91.4 to
      100.2 (P > 0.05), 175.9 (P < 0.05) and 234.5 (P < 0.05) mmol l-1, respectively. A
      preliminary experiment showed that an infusion rate of 107 mumol kg-1 min-1
      mimics the postprandial increase in ruminal VFA. The basal plasma GH
      concentrations (2 to 4 h after the start of VFA infusion) and the area under the
      profiles for GH release in response to the intravenous GRF injection, which was
      done 4 h after the start of VFA infusion, were significantly decreased by the VFA
      infusion rates of 107 and 214 mumol kg-1 min-1. Furthermore, the VFA infusion
      noticeably increased basal plasma concentrations of insulin, but it scarcely
      changed the basal levels of glucagon, SRIF and glucose. From these results we
      conclude that an increase in the ruminal VFA concentration, even within the
      physiological range, would suppress GH secretion from the ovine anterior
      pituitary, and that the postprandial rise in the ruminal VFA concentration may be
      one of the factors normally suppressing GH secretion in sheep.

PMID- 9152627
TI  - Tumor necrosis factor-alpha mediates endotoxin induced suppression of
      gonadotropin-releasing hormone pulse generator activity in the rat.
AB  - Bacterial endotoxin lipopolysaccharide (LPS) is known to suppress gonadotropin
      secretion and this effect is assumed to be mediated by cytokines. In the present
      study, we examined whether LPS affected hypothalamic electrical activity
      associated with LH pulses, and whether tumor necrosis factor-alpha (TNF-alpha), a
      major cytokine induced by LPS, was involved in this process. Ovariectomized rats
      were fitted with chronically implanted electrode arrays in the mediobasal
      hypothalamus, and multiunit activity (MUA) was recorded under conscious,
      unrestrained conditions. Blood samples were withdrawn every 6 min through an
      indwelling atrial catheter or determining serum LH concentrations. Intravenous
      (i.v.) injection of LPS (1 microgram) suppressed characteristic increases
      (volleys) in MUA associated with LH pulses throughout the experimental period up
      to 5 h. This suppressive effect of LPS on MUA volleys was significantly
      attenuated by simultaneous intracerebroventricular (icv) injection of the
      antibody (50 ng) to TNF-alpha through an indwelling cannula in the lateral
      ventricle. These changes in MUA were faithfully reflected in the LH secretory
      pattern. Further, either i.v. (0.4-2 micrograms) or i.c.v. (20-250 ng) injection
      of TNF-alpha suppressed the frequency of MUA volleys and associated LH pulses in
      a dose-dependent manner. These results suggest that LPS leads to the suppression
      of gonadotropin-releasing hormone pulse generator activity through a mechanism
      involving TNF-alpha.

PMID- 9152628
TI  - Detection of growth hormone gene defects by dideoxy fingerprinting (ddF).
AB  - We carried out screening for mutations in the GH-1 gene in 29 sporadic Japanese
      subjects with severe Isolated Growth Hormone Deficiency (IGHD) by dideoxy
      fingerprinting (ddF). Three of 29 (approximately 10%) were heterozygous for each
      of the following GH-1 gene mutations including: 1) an G-->A transition in the
      third codon of the GH-1 signal peptide of exon 1 resulting in a Threonine to
      Alanine substitution, 2) a G-->A transition in the first base of the donor splice
      site of IVS 3 (+1G-->A) and 3) a G-->A transition in the 183rd codon of the GH-1
      mature peptide of exon 5 resulting in an Arginine to Histidine substitution. One
      of three was heterozygous for both mutations of 1) and 2). The IVS 3 (+1G-->A)
      mutation has been previously reported in affected individuals from three
      unrelated families with IGHD type II (autosomal dominant form). This mutation
      destroys the GH IVS 3 donor splice site, causing skipping of exon 3 and loss of
      the codons for amino acids 32-71 of the mature GH peptide. Our findings indicate
      that 1) ddF screening of genomic DNAs provides a practical tool to detect GH gene
      mutations and 2) some sporadic cases of IGHD may be caused by GH gene
      alternations.

PMID- 9152630
TI  - Nutritional regulation of circulating insulin-like growth factors (IGFs) and
      their binding proteins in the ovine fetus.
AB  - Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are
      important for fetal and postnatal development, but the regulation of circulating
      IGFs and IGFBPs has not been as thoroughly investigated in the maternal/fetal
      unit as in the adult animal where nutrition status plays a regulatory role. We
      used the chronically-catheterized, late-gestation ovine model and compared
      circulating IGFs and IGFBPs levels, and hepatic IGF-I mRNA levels. Following a
      five-day maternal fast, both IGF-I and IGF-II levels were decreased in the
      maternal and fetal circulation (P < 0.05), accompanied by a decrease in fetal
      hepatic IGF-I mRNA levels, but the IGFBP2 level was increased and the IGFBP3
      level was decreased in maternal circulation, whereas the IGFBP1 level was
      increased in fetal circulation. In both fed and fasting states, the infusion of
      glucose (150% of baseline) did not alter IGFs or IGFBPs in either maternal or
      fetal circulation. To understand the regulation of the endogenous IGF system,
      rhIGF-I was infused (6.7 nmol/kg fetus/h) into the fetal circulation. While
      maternal IGFs or IGFBPs remained unchanged, IGF-I infusion into fetal circulation
      resulted in an increase in IGF-I, a decrease in IGF-II, and an overall increase
      in the IGFBPs (P < 0.05). Taken together, circulating IGFs and IGFBPs in the
      ovine fetus are more sensitive to prolonged nutrient deficit than to a brief
      glucose increase. The nutrition status therefore regulates the IGF system in
      maternal and fetal circulation which, in turn, may regulate the nutrient
      utilization for fetal growth.

PMID- 9152629
TI  - Expression of prolactin gene in mouse placenta during late pregnancy: detection
      of mRNA and its translation product.
AB  - To examine the existence of PRL messenger ribonucleic acid (mRNA) in the mouse
      placenta during late pregnancy, reverse transcriptase-polymerase chain reaction
      (RT-PCR) and Southern blot analysis were carried out followed by nucleotide
      sequence analysis of cDNA. Total RNA extracted from each tissue was reverse
      transcribed, followed by PCR with two oligonucleotide primers specific or a part
      of mouse PRL (mPRL) cDNA. An amplified RT-PCR product of predicted size was
      detected in all samples from the placenta of days 16 and 18 pregnant mice. This
      product was specifically hybridized with a probe overlapping an entire sequence
      of mPRL cDNA in Southern blot analysis. Nucleotide sequence analysis also
      provided evidence that the amplified cDNA had a nucleotide sequence completely
      identical to the mPRL cDNA sequence reported previously. Furthermore, mPRL with a
      slightly bigger molecular weight than that of pituitary PRL was detected in the
      placenta of days 12, 14, 16 and 18 pregnancy by immunoblot analysis. These
      results suggest that PRL mRNA and its translation product are synthesized in
      mouse placenta during late pregnancy.

PMID- 9152631
TI  - Lack of mutations of preproparathyroid hormone gene in three kindreds with
      familial isolated hypoparathyroidism.
AB  - The mutations of the preproparathyroid hormone (preproPTH) gene have been
      reported to cause some cases of familial isolated hypoparathyroidism (FIH). We
      investigated the preproPTH gene of five affected subjects of three Japanese
      kindreds with FIH. The mode of inheritance in FIH of two families was thought to
      be autosomal dominant, and the FIH of the other was probably inherited in an
      autosomal recessive manner. Exons 1, 2 and 3 of the preproPTH gene and its exon
      intron boundaries were analyzed with either polymerase chain reaction and single
      strand conformational polymorphism, or direct sequencing of the amplified DNA. We
      did not detect any mutations in the amplified regions of the preproPTH gene, but
      an A to G transition in intron 1 was identified in all of the affected subjects.
      Among them, four were heterozygote, and the other was homozygote. This transition
      was considered to be a polymorphism, which was the same as reported previously.
      These results indicate that the preproPTH gene abnormalities are not responsible
      for FIH in these families. Further studies are required to elucidate whether
      genes coding for other molecules, such as calcium-sensing receptor, are involved
      in FIH.

PMID- 9152632
TI  - Effect of CL316,243, a highly specific beta(3)-adrenoceptor agonist, on lipolysis
      of epididymal, mesenteric and subcutaneous adipocytes in rats.
AB  - To clarify whether a beta(3)-adrenoceptor agonist is more lipolytic in the
      visceral adipocytes than in the subcutaneous adipocytes, the lipolysis induced by
      CL316,243, a highly specific beta(3)-adrenoceptor agonist (relative selectivities
      of 0, 1 and 10,000 for beta(1)-, beta(2)- and beta(3)-receptors, respectively)
      was investigated in adipose tissue from rats. White adipocytes were prepared from
      the subcutaneous, mesenteric, and epididymal white adipose tissues of male Wistar
      rats (weighing about 150 g). Our findings showed that lipolysis of white
      adipocytes was stimulated both by the non-specific beta-adrenoceptor agonist,
      isoproterenol, and by the beta(3)-specific adrenoceptor agonist, CL316,243, but
      the lipolytic sensitivity to CL316,243 was about 10 times greater than that to
      isoproterenol in these three adipose tissues. Both isoproterenol and CL316,243
      induced more noticeable lipolysis in the epididymal and mesenteric than in the
      subcutaneous adipose cells in terms of the pD2 value [-log mol l-1 for EC50 (the
      concentration of an agonist giving half of its own maximum stimulation)]. These
      findings show that CL316,243 is more lipolytic in the visceral adipose cells than
      in the subcutaneous adipose cells, although epididymal adipose cells showed a
      high lipolytic response close to those observed in visceral adipose cells.
      CL316,243 may therefore be especially useful for the treatment of visceral fat
      type obesity related to various diseases.

PMID- 9152633
TI  - Measuring serum thyroglobulin in patients with follicular thyroid nodule: its
      diagnostic implications.
AB  - To determine the diagnostic implications of measuring the serum thyroglobulin
      level in patients with a solitary follicular thyroid tumor, a retrospective study
      was conducted on 122 consecutive patients with a solitary follicular thyroid
      nodule who underwent thyroidectomy. Data for eight variables were collected: the
      serum thyroglobulin (Tg) level (microgram/l), age, maximum diameter of the
      nodule, gender, histopathologic type, presence or absence of metastases,
      macroscopic characteristics of the cut surface of the resected tumor, and smoking
      habit. Multiple regression analyses were used to investigate the relationships
      between the serum Tg level and the seven other variables. The diagnostic value of
      serum Tg was examined by means of receiver operating characteristic (ROC) curves.
      There were significant correlations between the serum Tg level and the maximum
      diameter of the nodule, the macroscopic characteristics, and the smoking habit.
      The sensitivity and specificity of the serum Tg level with a cut-off value of
      1,000 micrograms/l were 57% and 86%, respectively. The likelihood ratio favouring
      follicular carcinoma associated with the serum Tg > 1,000 micrograms/l was 4.41.
      Measuring the level of serum Tg may be useful in discriminating follicular
      carcinoma from follicular adenoma, but since there may be some biases in this
      retrospective study, the results are less definitive. Further research activities
      are mandatory to obtain valid evidence.

PMID- 9152634
TI  - Competitive enzyme immunoassay for bovine growth hormone.
AB  - We developed an enzyme immunoassay (EIA) for bovine GH (bGH) which is based on
      indirect competitive immunoassay in culture medium from a bovine pituitary cell
      culture. 40 microliters cell culture samples (or bGH standard) and bGH antibody
      (rabbit anti-bGH) were added to the 96 well microplate coated with secondary
      antibody (Goat anti-rabbit IgG), and incubated for 24 h at 37 degrees C. Biotin
      label bGH was added and incubated further for 24 h at 37 degrees C, and
      biotinylated bGH was linked with streptoavidin-peroxidase. Substrates for
      peroxidase were added to the plate and incubated for 1 h at 4 degrees C. The
      enzyme reaction was stopped with 4N H2SO4, and the absorbency at 450 nm was
      measured with an ELISA Reader. The coefficients of intra-assay and inter-assay
      variations were 4.13 approximately 7.59% and 3.71 approximately 8.27%,
      respectively. The regression equation and correlation coefficients with the
      radioimmunoassay (RIA) were y(RIA) = 1.9986 x (EIA) - 1.3921 and 0.9701 (n = 27),
      respectively. Collectively, the present assay provides a reliable alternative to
      RIA and offers the major advantage of eliminating radioactive reagents and
      counting equipment.

PMID- 9152635
TI  - Non-Hodgkin's lymphoma presenting as thyroid and adrenal gland involvement.
AB  - We report an unusual case of non-Hodgkin's lymphoma involving both the thyroid
      and adrenal glands. Malignant infiltration of the glands by B-cell immunoblastic
      type lymphoma were demonstrated by cytologic findings in needle biopsy. Staging
      studies showed minor nodal involvement. The patient was treated with combination
      chemotherapy. Simultaneous involvement of the thyroid and adrenal glands with non
      Hodgkin's lymphoma is very rare. In this report, while presenting this rare
      coexistence, we also want to emphasize that fine-needle aspiration biopsy was
      useful in the diagnosis.

PMID- 9152636
TI  - Natural history of mitral regurgitation due to flail leaflets.

PMID- 9152637
TI  - A new treatment for hypertrophic cardiomyopathy?

PMID- 9152638
TI  - Contribution of heart rate variability to long-term risk stratification after
      myocardial infarction.

PMID- 9152639
TI  - Treatment of mild heart failure: the place of diuretics and ibopamine.

PMID- 9152640
TI  - Stress echocardiography and myocardial contrast echocardiography in viability
      assessment.

PMID- 9152641
TI  - Parallel testing: is it 'T-time'?

PMID- 9152643
TI  - Predictors of outcome of reperfusion therapy.
AB  - The physician wishing to estimate the risk of death for a patient experiencing
      acute myocardial infarction can rapidly use parameters available on first seeing
      the patient to estimate the expected mortality and can update this risk during
      the early phase of the event. From the initial evaluation, factors that exclude
      patients from reperfusion therapy constitute a substantially elevated risk. Older
      age, haemodynamic distress, and markers of ongoing ischaemia provide a large
      amount of prognostic information from the initial exam. Careful surveillance for
      additional complications allows continuous risk assessment during the early
      course.

PMID- 9152642
TI  - Antioxidant vitamins in the prevention of cardiovascular disease. The
      epidemiological evidence.

PMID- 9152644
TI  - The treatment of heart failure. Task Force of the Working Group on Heart Failure
      of the European Society of Cardiology.

PMID- 9152645
TI  - Serum cholesterol and long-term prognosis in middle-aged men with myocardial
      infarction and angina pectoris. A 16-year follow-up of the Primary Prevention
      Study in Goteborg, Sweden.
AB  - OBJECTIVE: To compare the role of serum cholesterol in the long-term prognosis of
      men with a history of myocardial infarction, in men with clinical angina without
      myocardial infarction, and men without clinical coronary disease. METHODS: In the
      second screening of the Primary Prevention Study in Goteborg which comprised 7100
      men aged 51 to 59 years at baseline in 1974-1977, 314 men with clinical angina
      but no myocardial infarction at baseline were identified and 195 men who had
      survived a myocardial infarction for 0 to 19 years (median 3 years). RESULTS: Of
      the men without clinical coronary disease at baseline and cholesterol at or below
      5.2 mmol.l-1, 2.7 per 1000 observation years died from coronary disease compared
      to 8.5 per 1000 of the men with serum cholesterol of 7.2 mmol.l-1 or more.
      Corresponding figures for men with angina was 5.5 and 31.0 per 1000 observation
      years, and for men with prior myocardial infarction 19.8 and 58.3, respectively,
      per 1000. After adjustment for age, smoking, systolic blood pressure, body mass
      index and diabetes the risk of coronary death in men with serum cholesterol above
      7.2 mmol.l-1 compared to below 5.2 mmol.l-1 was 2.42 (1.66-3.51) in healthy men,
      4.82 (1.44-16.09) in men with angina, 2.70 (0.95-7.67) in survivors of myocardial
      infarction, and 4.07 (1.86-8.91) in the combined group of men with either angina
      or prior infarction. The strongest effect was seen during the first half of the
      follow-up, with an adjusted relative risk for high in relation to low serum
      cholesterol of 8.08 (1.95-33.55) in men with preexisting coronary disease. Non
      coronary deaths varied little by serum cholesterol or coronary disease status at
      baseline. After 16 years, 76% of the healthy men with low cholesterol and 65% of
      healthy men with cholesterol above 7.2 mmol.l-1 were still alive. Of the men with
      prior myocardial infarction, 50% in the group with low cholesterol were alive
      after 16 years, as compared to 21% of those with high cholesterol. CONCLUSION:
      The long-term absolute risk of death in men with coronary disease and elevated
      serum cholesterol is very high. Implementation of lipid-lowering strategies shown
      to be efficacious is important in this high-risk group.

PMID- 9152646
TI  - Risk stratification in unstable coronary artery disease. Additive value of
      troponin T determinations and pre-discharge exercise tests. FRISK Study Group.
AB  - In 963 patients, participating in a randomized study of low molecular weight
      heparin in unstable coronary artery disease and followed for 5 months, troponin T
      was determined. In the 766 patients with a pre-discharge exercise test both
      troponin T level and exercise test response were independent predictors of
      prognosis. Cardiac death or myocardial infarction occurred in 5, 9 and 13% of the
      patients with a maximal troponin T level of < 0.06 (n = 154), 0.06-0.2 (n = 175)
      and > or = 0.2 microgram.l-1 (n = 437), respectively. Based on exercise tolerance
      and occurrence of ST depression, patients with a low (n = 361), intermediate (n =
      325) and high risk (n = 80) exercise test response were identified. In these,
      death or myocardial infarction occurred in 5, 13 and 29%, respectively. The
      combination of troponin T and the exercise test response allowed an even better
      categorization into low (n = 84), intermediate (n = 406) and high (n = 276) risk
      groups with 1, 7 and 20% death or myocardial infarction, respectively. Among
      those 197 patients unable to perform an exercise test the incidence was 3, 16 and
      27% in patients with troponin T < 0.06, 0.06-0.2 and > or = 0.2 microgram.l-1,
      respectively. Thus, troponin T determinations and pre-discharge exercise tests
      alone and combined are valuable for risk assessment in unstable coronary artery
      disease.

PMID- 9152647
TI  - Combined use of dobutamine echocardiography and myocardial contrast
      echocardiography in predicting regional dysfunction recovery after coronary
      revascularization in patients with recent myocardial infarction.
AB  - BACKGROUND: Myocardial contrast echocardiography and dobutamine echocardiography
      have recently emerged as potentially useful clinical tools to detect reversible
      myocardial dysfunction. However, the relative accuracy of these two techniques in
      predicting regional wall motion improvement after coronary interventions is still
      unclear. The aim of the present study was to compare their diagnostic value in
      predicting functional recovery after coronary revascularization in patients with
      recent acute myocardial infarction. METHODS AND RESULTS: Twenty-four patients
      with acute myocardial infarction underwent myocardial contrast echocardiography
      and dobutamine echocardiography within 2 weeks of hospital admission. Infarct
      zone contrast score and wall motion score indexes were derived in each patient.
      Infarct-related artery revascularization was performed before hospital discharge
      in all selected patients. Resting echocardiography was repeated 3 months after
      revascularization, and regional function recovery was analysed. The degree of
      wall motion score improvement at 3-month follow-up and the percentage of positive
      responses to dobutamine echo were greater (P < 0.001 and P < 0.002, respectively)
      in patients with a higher baseline contrast score (> or = 0.50). Conversely, no
      significant changes were observed either during dobutamine echo or after
      revascularization in the group of patients without residual perfusion within the
      infarct area. Diagnostic agreement between both techniques in predicting
      reversible dysfunction was high (81% of segments). The sensitivity and negative
      predictive value in predicting functional outcome were 100% (95% confidence
      interval [CI], 87% to 100%) and 100% (95% CI, 93% to 100%) by contrast echo, and
      85% (95% CI, 66% to 96%) and 93% (95% CI, 84% to 98%) by dobutamine echo. The
      specificity and positive predictive value were 90% (95% CI, 80% to 96%) and 81%
      (95% CI, 64% to 93%) by contrast echo, and 88% (95% CI, 78% to 95%) and 76% (95%
      CI, 58% to 90%) by dobutamine echo. The combination of myocardial contrast and
      dobutamine echocardiography positive responses improved specificity and positive
      predictive value in detecting functional recovery after revascularization to 100%
      (95% CI, 94% to 100%) and 100% (95% CI, 85% to 100%), respectively. However, the
      sensitivity and negative predictive value slightly decreased with the use of both
      methods (85% [95% CI, 66% to 96%)] and (93%[95% CI, 85% to 98%)], respectively.
      CONCLUSIONS: In patients with recent myocardial infarction, reversible
      dysfunction after coronary revascularization and the response to dobutamine
      infusion are strictly dependent on microvascular integrity. However,
      microvascular perfusion does not always imply functional recovery after coronary
      revascularization. The integration with dobutamine echo results seems
      particularly helpful to further improve myocardial contrast echo specificity and
      positive predictive values.

PMID- 9152648
TI  - Non-invasive risk stratification within 48 h of hospital admission in patients
      with unstable coronary disease.
AB  - AIMS: In this study we evaluated the prognostic value of three methods of early
      risk estimation in patients with unstable coronary disease. METHODS AND RESULTS:
      The methods evaluated were: clinical risk estimation at hospital admission,
      continuous ST analysis with computerized vectorcardiography for 24 h and serial
      measurements of creatinine kinase-MB for 48 h. Twenty-seven (14%) of the 195
      patients died or had a non-fatal infarction within one year. Clinical risk
      evaluation correctly identified a subgroup of patients with low risk but did not
      otherwise predict outcome. Fifty-six (29%) patients had ST vector magnitude
      episodes on vectorcardiography, 70 (38%) had three or more episodes of ST change
      vector magnitude and 74 (38%) had a peak creatinine kinase-MB value of 6
      microgram.l-1 or more. The even rate for patients with ST vector magnitude
      episodes (23%) was significantly higher than for those without (10%; P < 0.05).
      For patients with and without three or more episodes of ST change vector
      magnitude the event rate was 23% and 9% respectively (P < 0.05) and for patients
      with and without creatinine kinase-MB > or = 6 microgram.l-1 the event rate was
      23% and 8% respectively (P < 0.01). The positive predictive value of having none,
      either one or both of the ST or creatinine kinase-MB markers positive was
      incremental. CONCLUSION: Continuous vectorcardiographic monitoring of ischaemia
      in combination with serial creatinine kinase-MB measurement considerably improves
      risk stratification in unstable coronary disease.

PMID- 9152649
TI  - Heart rate variability as a means of assessing prognosis after acute myocardial
      infarction. A 3-year follow-up study.
AB  - AIMS: The present study evaluated the prognostic value of heart rate variability
      after acute myocardial infarction in comparison with other known risk factors.
      The cut-off points that maximized the hazards ratio were also explored. PATIENTS
      AND METHODS: Heart rate variability was assessed with 24 h ambulatory
      electrocardiography in 74 patients with acute myocardial infarction, 4 +/- 2 days
      after hospital admission and in 24 healthy controls. Patients were followed for
      36 +/- 15 months. RESULTS: During follow-up, 18 patients died, nine suffered a
      non-fatal infarction and 20 underwent revascularization procedures. Heart rate
      variability was higher in survivors than in non-survivors (P = 0.005). This
      difference was found at higher statistical levels when comparing non-survivors vs
      controls (P = 0.0002). A similar statistically significant difference was also
      found between survivors vs controls (P = 0.04). Patients suffering non-fatal
      infarction and cardiac events (defined as death, non-fatal infarction or
      revascularization) had a lower heart rate variability than those without (P =
      0.03 and P = 0.03, respectively). With multivariate regression analysis,
      decreased heart rate variability independently predicted mortality and death or
      non-fatal infarction. The presence of a left ventricular ejection fraction < 40%
      and a history of systemic hypertension were, however, stronger predictors. The
      cut-off points that maximized the hazards ratio using the Cox model differed from
      those reported by others. CONCLUSION: Decreased heart rate variability
      independently predicted poor prognosis after myocardial infarction. However, the
      cut-off points that should be used in clinical practice are still a matter for
      further investigation.

PMID- 9152650
TI  - An assessment of dobutamine echocardiography and end-diastolic wall thickness for
      predicting post-revascularization functional recovery in patients with chronic
      coronary artery disease.
AB  - AIMS: This study investigated the functional outcome of wall-thinned, akinetic
      myocardium after revascularization and evaluated the accuracy of dobutamine
      echocardiography in predicting post-revascularization functional recovery with
      the assessment of end-diastolic wall thickness in chronic ischaemic patients.
      METHODS AND RESULTS: Fifty-three patients underwent dobutamine echocardiography
      before coronary revascularization. End-diastolic wall thickness was also
      evaluated before and after revascularization. The sensitivity and specificity of
      dobutamine echocardiography to predict postrevascularization functional recovery
      were 69% and 100% in 58 akinetic/dyskinetic segments, and 86% and 57% in 96
      hypokinetic segments. Of 19 akinetic/dyskinetic segments with a preserved end
      diastolic wall thickness, 17 (89%) showed functional recovery after
      revascularization, and dobutamine detected 14 (83%) of these 17 segments. Of 39
      akinetic/dyskinetic segments with a thinned end-diastolic wall thickness, 15
      (38%) achieved functional recovery, whereas dobutamine echocardiography detected
      recovery in only eight (53%). Further, of these 15 viable, Wall-thinned segments,
      12 (80%) showed an increased end-diastolic wall thickness after revascularization
      (mean +/- SD were from 5.6 +/- 0.7 mm at baseline to 7.4 +/- 1.3 mm and 9.7 +/-
      1.4 mm after 1 week and after 3 months, respectively), and only 5 (42%) of these
      responded to dobutamine. CONCLUSION: Dobutamine echocardiography showed a
      lessened sensitivity to predict post-revascularization functional recovery in
      akinetic/dyskinetic segments with a thinned end-diastolic wall thickness that
      subsequently increased in size.

PMID- 9152651
TI  - Effects of mental and physical stress on platelet function in patients with
      stable angina pectoris and healthy controls.
AB  - The effects of mental and physical stress on platelet function in patients with
      stable angina pectoris and healthy controls were investigated. Platelet function
      was studied at rest, and during mental stress (colour word test), or after
      exercise (bicycle ergometry), in 113 angina patients (21 on aspirin) and 50
      matched controls. Platelet function was assessed by filtragometry ex vivo
      (reflecting platelet aggregability), by measuring platelet secretion (beta
      thromboglobulin and platelet factor 4 levels in plasma), and by Born aggregometry
      in vitro. At rest, platelet function did not differ between patients and
      controls. Exercise increased platelet aggregability and secretion similarly in
      both groups. Aspirin did not attenuate the platelet activating effect of exercise
      despite inhibition at rest. Mental stress increased heart rate, blood pressure
      and plasma catecholamines, but platelet responses were highly variable. However,
      mental stress tended to shorten filtragometry readings in patients but not in
      controls (P < 0.05 between the groups); plasma beta-thromboglobulin showed a
      similar difference between patients and controls (P < 0.05 between the groups;
      aspirin-treated patients included). Physical exercise activates platelets in
      patients with stable angina pectoris and healthy controls. Aspirin is not an
      effective inhibitor of exercise-induced platelet aggregation. Platelet responses
      to mental stress are variable, but more pronounced in angina patients.

PMID- 9152652
TI  - Trends in coronary heart disease morbidity and mortality and acute coronary care
      and case fatality from 1985-1989 in southern Germany and south-western France.
AB  - BACKGROUND: Although it has been shown that coronary heart disease mortality
      rates are decreasing in industrialized countries, little is known about time
      trends in coronary heart disease incidence. Further, although a number of
      randomized clinical trials have shown that percutaneous transluminal coronary
      angioplasty and thrombolysis improve survival of acute myocardial infarction
      patients, it is not known if widespread use of these therapeutic procedures has
      contributed to a decrease in in-hospital case fatality on a population basis.
      METHODS: The change over time of coronary heart disease attack, incidence and
      mortality rates was assessed in men and women (35 to 64 years) using data
      collected between 1985 and 1989 by the Augsburg (Germany) and Toulouse (France)
      MONICA Centres. Acute coronary care and 28-day case fatality for hospitalized 24
      h survivors were also assessed. RESULTS: Men and women from Augsburg had higher
      age-standarized attack, incidence and mortality rates than their Toulouse
      counterparts. In both centres, attack, incidence and mortality rates declined in
      men, but increased in women. Patients in Toulouse received more percutaneous
      transluminal coronary angioplasty and thrombolysis and had lower 28-day case
      fatality than patients in Augsburg. The therapeutic procedures, percutaneous
      transluminal coronary angioplasty and thrombolysis increased in both centres;
      however, only in Toulouse was this increase associated with a decrease (non
      significant) in 28-day hospital case fatality. CONCLUSION: The increase in
      morbidity and mortality rates of coronary heart disease in women stresses the
      need for preventive measures in this group. The absence of a favourable effect of
      acute coronary care on 28-day fatality for hospitalized 24-h survivors in the
      Augsburg centre will be further investigated.

PMID- 9152653
TI  - Submaximal early exercise test compared to clinical findings for evaluation of
      short- and long-term prognosis after the first myocardial infarction. Result from
      the MONICA Projects in Augsburg and Toulouse.
AB  - Clinical and ergometric data were derived from 1098 consecutive exercise tests in
      patients with a first acute myocardial infarction between 1974-1983. In 1992 a
      follow-up was performed in order to analyse the importance of a submaximal early
      exercise test, in combination with clinical data, for the prediction of short-
      and long-term prognosis of cardiovascular death. The relative value of 20
      clinical variables, including medical history, markers of infarction size,
      medication etc., and 28 variables at exercise test were studied. Univariate,
      multivariate and survival analysis, for estimation of prognosis and independent
      prediction of cardiovascular death was used. Independent clinical risk factors
      for cardiovascular death were (1) Within 1 year: relative heart volume (ml.m-2
      body surface area) on chest X-ray. (2) Long-term mortality: maximum heart rate
      and relative heart volume, diabetes, age and digitalis medication. Independent
      exercise risk factors were: (1) Within 1 year: heart rate, ventricular arrhythmia
      and ST depression > or = 1 mm before exercise, diastolic blood pressure at
      maximum exercise and target heart rate. (2) Long-term mortality: angina pectoris
      and/or ST depression > or = 1 mm at maximum exercise. In subgroups of patients
      with clinical risk factors, mortality risk increased if there were signs of
      angina pectoris and/or ST depression > or = 1 mm during exercise. The risk
      increased 100% in diabetics, 91% with age > 70 years, 58% with relative heart
      volume > or = 500 ml.m-2 body surface area, 42% with heart rate > or = 100 at
      admission, and 34% with digitalis medication. No increase was found in the
      subgroup of patients without clinical risk factors. Thus, submaximal early
      exercise stress testing provides important information for short- and long-term
      prognosis in patients after the first acute myocardial infarction compared to
      clinical evaluation alone.

PMID- 9152654
TI  - Role of interactions between psychological and clinical factors in determining 6
      month mortality among patients with acute myocardial infarction. Application of
      recursive partitioning techniques to the GISSI-2 database. Gruppo Italiano per lo
      Studio della Sopravvivenza nell' Infarto Miocardico.
AB  - BACKGROUND: Clinical and epidemiological studies support the hypothesis that
      ischaemic cardiovascular diseases are consistently associated with psychological,
      social and behavioural factors. Nevertheless, the joint effect of clinical
      characteristics and psychological variables in determining the prognosis of acute
      myocardial infarction survivors has been seldom investigated. METHODS AND
      RESULTS: In the framework of the GISSI-2 trial, the impact of psychological
      factors on 6-month mortality and their interaction with clinical features was
      included as an ad hoc research project. Overall, 2449 patients were evaluated, 63
      of whom died during the study period. All patients undertook a self-administered
      questionnaire (Cognitive Behavioural Assessment Hospital Form), investigating 16
      psychological dimensions relative to three areas (state variables, vital
      exhaustion, trait variables). The impact of psychological variables on prognosis
      and their interaction with clinical variables were investigated by using a tree
      growing technique (RECursive Partitioning and AMalgamation-RECPAM) applied to
      survival analysis. This statistical method allowed the identification of three
      separate classes, characterized by different prognoses: Class I (presence of
      vital exhaustion), Class II (concomitance of no vital exhaustion, depression and
      low levels of anxiety) and Class III (all other patients). After adjusting for
      the clinical variables, Class I was associated with an intermediate prognosis
      (hazard ratio [HR] = 2.2; 95% confidence intervals [CI], 1.2-4.0) and Class II to
      the worst (HR = 3.2; 95% CI = 1.6-6.2), as compared to Class III. High levels of
      neuroticism and extroversion were associated with a better prognosis. When
      clinical and psychological variables were simultaneously investigated by RECPAM,
      Type A behaviour was shown to be an important risk predictor among patients with
      better clinical conditions, i.e. those eligible for exercise test (HR = 2.6, 95%
      CI = 1.2-5.5). Finally, a striking difference in the impact of the most
      predictive clinical variables (exercise test ineligibility, late and early
      ventricular failure) was found among patients with and without vital exhaustion.
      CONCLUSIONS: This study shows that acute myocardial infarction survivors are
      heterogeneous with respect to 6-month mortality according to their psychological
      profile. More important, the impact of these variables appears comparable to that
      of very well known clinical risk predictors. The availability of a large study
      population, together with the use of innovative statistical techniques, allowed
      us to identify subgroups of patients for whom the joint action of clinical and
      psychological characteristics has been clearly documented. This suggests the need
      for incorporating psychological evaluation in the care of acute myocardial
      infarction patients.

PMID- 9152655
TI  - Induction of subaortic septal ischaemia to reduce obstruction in hypertrophic
      obstructive cardiomyopathy. Studies to develop a new catheter-based concept of
      treatment.
AB  - AIM: To develop a new catheter-based method of treatment in patients with
      hypertrophic obstructive cardiomyopathy. METHOD: Does abolition of the blood
      supply to the subaortic part of the septum lead to regional myocardial ischaemia
      and a decrease in the left ventricular outflow tract gradient? To find this out,
      in 10 consecutive patients the first larger septal branch of the left anterior
      descending coronary artery was temporarily occluded with conventional
      percutaneous transluminal coronary angioplasty. The intracoronary
      electrocardiogram was registered for objective verification of the intended
      ischaemia. The intraventricular pressure was measured at rest and at the post
      extrasystolic beat under programmed electrostimulation of the right ventricle.
      RESULTS: During occlusion, regional ischaemia was observed in all patients.
      Simultaneously, there was a significant reduction of the intraventricular
      gradient from 56.2 mmHg to 32.2 mmHg (P < 0.05) followed by an increase from 32.2
      mmHg to 61.1 mmHg (P < 0.01) after release of occlusion of the septal branch.
      During ischaemia there was no increase in left ventricular end-diastolic
      pressure. CONCLUSION: We conclude that the results form the basis for a new
      catheter interventional therapy in hypertrophic obstructive cardiomyopathy.

PMID- 9152656
TI  - A double-blind, cross-over comparison of the effects of a loop diuretic and a
      dopamine receptor agonist as first line therapy in patients with mild congestive
      heart failure.
AB  - We compared the effects of the orally active dopamine agonist ibopamine with the
      loop diuretic frusemide as first-line therapy in patients with mild congestive
      heart failure. Fourteen patients with New York Heart Association class II
      congestive heart failure were enrolled in a double-blind, cross-over study. After
      baseline measurements of clinical and symptomatic status, modified Bruce exercise
      time, high-level exercise time, corridor walk time, regional blood flow,
      pedometer scores, 24 h urine volume and sodium excretion and neurohumoural
      factors, patients were randomly allocated to receive either frusemide 40 mg o.d.
      or ibopamine 100 mg t.d.s. for 8 weeks. Assessments were performed at 2 weekly
      intervals. After 8 weeks, patients crossed over into the alternate treatment arm
      for a further 8 weeks, with further assessments performed every 2 weeks. There
      were four exacerbations of heart failure during ibopamine treatment and none
      during frusemide treatment. After 8 weeks of treatment, modified Bruce exercise
      time was 901 +/- 73 s with frusemide and 646 +/- 134 s with ibopamine (P < 0.05).
      Twenty-four hour urinary sodium excretion at weeks 2 and 4 (P < 0.05), and 24 h
      urinary volume at week 2 (P = 0.0001) were lower during ibopamine treatment. At
      week 8, supine (P = 0.076) and erect renin (P = 0.05) were lower with ibopamine
      treatment. In conclusion, ibopamine is ineffective as first line therapy for
      congestive heart failure, probably because of a lesser diuretic potency than
      frusemide.

PMID- 9152657
TI  - Serum uric acid as an index of impaired oxidative metabolism in chronic heart
      failure.
AB  - BACKGROUND: Elevated serum uric acid concentrations have been observed in
      clinical conditions associated with hypoxia. Since chronic heart failure is a
      state of impaired oxidative metabolism, we sought to determine whether serum uric
      acid concentrations correlate with measures of functional capacity and disease
      severity. METHODS: Fifty nine patients with a diagnosis of chronic heart failure
      due to coronary heart disease (n = 34) or idiopathic dilated cardiomyopathy (n =
      25) and 20 healthy controls underwent assessment of functional capacity. Maximal
      oxygen uptake (MVO2) and regression slope relating to minute ventilation to
      carbon dioxide output (VE-VCO2) were measured during a maximal treadmill exercise
      test. Metabolic assessment consisted of measuring serum uric acid and fasting
      lipids, and insulin sensitivity, obtained by minimal modelling analysis of
      glucose and insulin responses during an intravenous glucose tolerance test.
      Clustering of indices of functional disease capacity and metabolic factors was
      explored using factor analysis and multivariate regression analysis. RESULTS:
      Compared to 20 healthy controls, patients with chronic heart failure had a 52%
      lower MVO2 (P < 0.001), 56.8% higher serum uric acid concentrations (P < 0.001)
      as well as a 60.5% lower insulin sensitivity (P < 0.001). Salient univariate
      correlations in the chronic heart failure group included serum uric acid
      concentrations with exercise time during the exercise test (r = -0.53), MVO2 (r =
      -0.50) (both P < 0.001), VE-VCO2 slope (r = 0.45), and NYHA functional class (r =
      0.36) (both P < 0.01). In factor analysis of the chronic heart failure group,
      serum uric acid formed part of a principal cluster of metabolic variables which
      included MVO2 and VE-VCO2 slope. In multivariate regression analysis, serum uric
      acid concentrations emerged as a significant predictor of MVO2, exercise time
      (both P < 0.001,) VE-VCO2 slope and NYHA functional class (both P < 0.02),
      independent of diuretic dose, age, body mass index, serum creatinine, alcohol
      intake, plasma insulin levels, and insulin sensitivity index. CONCLUSIONS: There
      is an inverse relationship between serum uric acid concentrations and measures of
      functional capacity in patients with cardiac failure. The strong correlation
      between serum uric acid and MVO2 suggests that in chronic heart failure, serum
      uric acid concentrations reflect an impairment of oxidative metabolism.

PMID- 9152660
TI  - Variation in mode of sudden cardiac death in patients with dilated
      cardiomyopathy.

PMID- 9152659
TI  - Heart transplantation in patients over 54 years of age. Mortality, morbidity and
      quality of life.
AB  - AIMS: As a consequence of recent advances in heart transplantation, upper age
      limits for the procedure have been liberalized in many centres. It was the
      purpose of this study to compare post-transplant mortality, morbidity and quality
      of life in a consecutive series of 72 patients > 54 years (mean age, 57.6 +/- 2.7
      years) with a control group of 72 adult patients < or = 54 years (mean age, 42.4
      +/- 9.5 years) transplanted at one centre between 1985 and 1991. METHODS AND
      RESULTS: Patients were followed for 41 +/- 27 months post-transplant. Actuarial 1
      , 5- and 7-year survival rates were 78 +/- 5%, vs 81 +/- 5%, 52 +/- 7% vs 66 +/-
      6% and 46 +/- 8% vs 63 +/- 6% in patients > 54 years and < or = 54 years,
      respectively (P = ns). Causes of death were not significantly different between
      the groups. Patients > 54 years experienced significantly fewer rejection
      episodes after the 6th month post-transplant (0.5 +/- 0.9 vs 0.9 +/- 1.0, P <
      0.04), and incidence and treatment of rejection episodes as well as incidence of
      infection was comparable between the groups. Non-lymphoid malignancies, mainly
      skin cancer, occurred more often in the older age group (27% vs 13%, P < 0.05).
      Quality of life, as assessed by the Nottingham Health Profile, was better in 5/6
      dimensions of social functioning in older patients and the difference reached
      statistical significance for the dimensions of emotional reactions (P = 0.005)
      and sleep (P = 0.0005). CONCLUSION: In conclusion, carefully selected patients >
      54 years can undergo heart transplantation with mortality and morbidity
      comparable to younger patients. Quality of life post-transplant seems even to be
      slightly better in the older age group.

PMID- 9152658
TI  - Facilitating influence of procainamide on conversion of atrial flutter by rapid
      atrial pacing.
AB  - In a prospective, double-blind, randomized, placebocontrolled study we
      investigated the facilitating influence of intravenous procainamide on conversion
      of atrial flutter by rapid atrial pacing. Fifty consecutive patients with
      spontaneous sustained atrial flutter were 1:1 randomized into two homogenous
      groups: group A received 10 mg.kg-1 procainamide intravenously, group B placebo.
      After infusion there was a significant (P < 0.01) lengthening of the flutter
      cycle with respect to baseline in group A, exceeding the flutter cycle length of
      the control group (P < 0.05). The overall success rate of rapid atrial pacing in
      restoring sinus rhythm was significantly higher after pre-treatment with
      procainamide compared to placebo (100% vs 76%; P < 0.05): 20 patients of group A
      reverted immediately after pacing to sinus rhythm, the remaining five after a
      brief episode of atrial fibrillation. In the placebo group, 16 patients showed a
      prompt conversion to sinus rhythm and three after transient atrial fibrillation.
      In the remaining six patients, due to sustained pacing-induced atrial
      fibrillation, direct current cardioversion was necessary. After administration of
      procainamide a less aggressive stimulation protocol with significantly (P < 0.01)
      longer paced cycles to interrupt atrial flutter was achievable. In conclusion,
      intravenous procainamide augments the efficacy of atrial pacing to convert atrial
      flutter to sinus rhythm.

PMID- 9152661
TI  - Primary chylopericardium due to partial aplasia of the thoracic duct.

PMID- 9152663
TI  - Stable angina: drugs, angioplasty or surgery?
AB  - Stable angina is a common condition with a good overall prognosis and annual
      mortality is 2-4%, whatever treatment is employed. Medical therapy with nitrates,
      beta-blockers, calcium antagonists and lipid-lowering agents is appropriate as
      first-line therapy in those patients not specifically identified as being at risk
      by exercise testing and/or angiography. Dosage should be optimized. Coronary
      artery bypass grafting appears to improve prognosis in those at risk when
      compared with medical therapy but the trials are old and do not take into account
      major advances in medical therapy nor the use of arterial conduits in coronary
      artery bypass grafting (CABG). Percutaneous transluminal coronary angioplasty
      (PTCA) relieves symptoms when medical therapy is ineffective but its role as an
      initial therapy has not been established, nor does it compare favourably with
      CABG with regard to the degree of revascularization and subsequent re
      intervention or need for additional anti-anginal drugs. There are little
      substantial data on prognostic effects. PTCA is, however, less traumatic, less
      expensive and associated with a quicker recovery than CABG, providing a viable
      alternative for symptomatic (not prognostic) benefit in appropriately selected
      and informed patients. Medical therapy, PTCA and CABG should not be seen as
      competitive but complementary strategies. Optimal utilization of all three
      treatment modalities, either alone or in combination, can provide substantial
      symptomatic relief for the angina patient.

PMID- 9152662
TI  - Magnesium sulphate in the treatment of ventricular fibrillation in amitriptyline
      poisoning.

PMID- 9152664
TI  - Treatment of ischaemic heart disease. Role of drugs, surgery and angioplasty in
      unstable angina patients.
AB  - The term unstable angina should only be used to describe patients whose immediate
      prognosis is uncertain and the nature of the unstable disease may vary on a
      patient to patient basis, making broad categorization of such patients
      inappropriate. Unstable angina may be caused by extracardiac factors, such as
      uncontrolled hypertension and tachycardia, disruption of an atheromatous plaque,
      dynamic or intermittent coronary artery thrombosis, haemorrhagic dissection into
      an atheromatous plaque, epicardial coronary spasm or progression of
      atherosclerosis as a result of plaque healing. Control of symptoms using medical
      therapy with a combination of nitrates, beta-blockers and calcium antagonists is
      usually quite successful. In the absence of contra-indications, intravenous
      heparin, and possibly anti-platelet agents, should also be used in the acute
      phase of treatment. In addition, one aspirin a day is indicated unless there are
      definite contra-indications. If symptoms are relieved, evaluation and management
      should proceed as with chronic stable angina. Identification of patients with a
      poor prognosis should be the main indication for urgent revascularization. One of
      the best predictors of a poor prognosis in unstable disease is persistent pain
      despite optimum therapy. Urgent surgery should be considered in any patient with
      multivessel coronary artery stenosis who has evidence of persistent myocardial
      ischaemia, despite adequate medical therapy.

PMID- 9152665
TI  - New trends in the interventional treatment of ischaemic heart disease.
AB  - Direct revascularization of an ischaemic vascular bed represents an attractive
      treatment option for patients with coronary artery disease. Coronary artery
      bypass surgery has been demonstrated to provide both symptomatic improvement and,
      in certain circumstances, to improve prognosis, while catheter-based techniques
      offer substantial improvement in symptomatology, with reduced morbidity compared
      with bypass surgery. Although balloon angioplasty has been associated with lesion
      success rates approximating to 89%, a number of anatomical substrates have proved
      refractory to this approach and restenosis remains a significant problem. Newer
      interventional modalities, such as directional atherectomy, rotablation,
      transluminal extraction catheterization, laser coronary angioplasty and coronary
      stenting, all have the potential to offer improved rates of restenosis under
      specific circumstances. With the exception of stents, most have not been shown to
      provide an overall improvement in rates of restenosis. Numerous pharmacological
      agents have also been investigated in an attempt to reduce levels of restenosis.
      Calcium channel blockers have been assessed in five trials, none of which has
      demonstrated a conclusive benefit, although meta-analysis of the data generated
      in these trials has shown a 30% reduction in the likelihood of restenosis
      associated with their use. More recently, monoclonal antibodies to glycoprotein
      IIb/IIIa have been linked to a reduction in restenosis.

PMID- 9152666
TI  - Clinical promise of calcium antagonists in the angioplasty patient.
AB  - Depending upon the definition used, restenosis occurs in 10-60% of patients who
      undergo percutaneous transluminal coronary angioplasty. Restenosis appears to be
      the result of a combination of pathophysiological processes, including elastic
      recoil of arterial walls, platelet deposition and thrombus formation and
      resultant fibro-cellular neointimal hyperplasia. A range of pharmacological
      interventions has been used in an attempt to reduce the rate of restenosis
      following angioplasty, with little success. Furthermore, many patients who
      undergo angioplasty still suffer from ischaemia after the procedure. Calcium
      antagonists, such as the long-acting dihydropyridine amlodipine, have been
      demonstrated to be effective in the control of both symptomatic and asymptomatic
      ischaemia and are, therefore, likely to be of utility for this purpose in
      angioplasty patients. Calcium antagonists also exhibit characteristics that may
      lead to a reduction in restenosis, in that they inhibit platelet aggregation,
      reduce vasoplasm and inhibit the action of mitogens which stimulate proliferation
      and migration of smooth muscle cells. The results of five trials of calcium
      antagonists in angioplasty patients have been individually unconvincing in terms
      of prevention of restenosis, only one trial demonstrated a significant effect.
      However, a meta-analysis of these results has demonstrated an approximately 30%
      reduction in the chance of restenosis in those patients treated with calcium
      antagonists. The Coronary Angioplasty Amlodipine in Restenosis (CAPARES) trial
      has been initiated to assess the impact of amlodipine upon the rate of restenosis
      and angina/ischaemia after the procedure.

PMID- 9152667
TI  - Pharmacological treatment of ischaemic heart disease. Monotherapy vs combination
      therapy.
AB  - Non-invasive treatment continues to be the mainstay of anti-ischaemic therapy.
      The imbalance between myocardial oxygen supply and demand provides the basis for
      myocardial ischaemia, which may present as symptomatic, asymptomatic or, in most
      cases, a mixture of the two. Both symptomatic and silent ischaemia are major
      prognostic indicators in patients with coronary artery disease and treatment
      should therefore be directed towards both the amelioration of symptoms and the
      resolution of the signs of ischaemia. Anti-ischaemic therapy may decrease oxygen
      demand, increase myocardial oxygen supply, or both. Interventional therapies,
      such as percutaneous transluminal coronary angioplasty and bypass grafting,
      improve supply but do not alter demand. Drug therapy is associated with a variety
      of effects upon both supply and demand, depending upon the agent used. Nitrates
      alter both myocardial oxygen supply and demand, while beta-blockers decrease
      myocardial oxygen demand. Calcium channel blockers reduce after load and
      myocardial contractility and, thus, lower oxygen demand, while the coronary
      artery relaxation that occurs in response to their use acts to increase supply.
      The use of combination therapy is considered by many to be the most rational
      approach to the treatment of myocardial ischaemia, in that it allows maximal
      reduction in demand and increase in supply.

PMID- 9152668
TI  - Is medical treatment for angina the most cost-effective option?
AB  - A meta-analysis of the benefits of coronary artery bypass graft (CABG) surgery
      has been used as the basis of a model for comparing the costs and benefits of
      surgical and medical treatment of angina pectoris. In order to allow for the
      results of recent research, the economic model included the addition of aspirin
      and aspirin plus an HMG-CoA reductase inhibitor (statin) to medical management.
      The analysis indicates that in unselected patients the cost-effectiveness of CABG
      vs initial standard medical therapy over 5 years is towards the upper limit of
      what can be considered a cost-effective treatment both in terms of its effect on
      mortality (life-years gained) and morbidity (quality adjusted life-years).
      Addition of a statin to medical therapy reduced mortality and made coronary
      artery bypass graft surgery an expensive option in terms of improvement of
      quality of life. In patients with three-vessel disease or left ventricular
      dysfunction surgery appears fairly cost-effective in comparison with standard
      medical therapy but becomes relatively expensive when the benefits of aspirin or
      lipid-lowering therapy are added to medical treatment.

PMID- 9152669
TI  - Supraventricular tachycardia. ECG diagnosis and anatomy.
AB  - This paper reviews the anatomical substrates responsible for the induction and
      maintenance of supraventricular tachycardia and discusses the ECG findings
      associated with these tachycardias. The normal anatomy of the supraventricular
      conducting system, particularly within the atria, is complex with conduction
      proceeding along preferential pathway, which are in turn determined in part by
      the anisotropic properties of the atrial myocardium. There appear to be at least
      dual inputs to the atrioventricular node, a posteriorly situated slow pathway and
      an anterior fast pathway. It is sometimes possible to relate ECG findings
      directly to anatomical substrates; for example, in some cases of atrial
      tachycardia the site of the atrial focus (left or right, superior or inferior)
      can be determined by the polarity of the P wave. The anatomical substrates
      responsible for intra-atrial re-entry, atrial flutter and atrial fibrillation
      relate to anatomical barriers to impulse propagation and areas of slow
      conduction. In atrial flutter the crista terminalis, Eustachian valve, inferior
      vena cava, coronary sinus os, and tricuspid annulus have been identified as
      anatomical barriers to conduction around which a macro re-entrant circuit within
      the right atrium may conduct, usually in a counter-clockwise direction. Clockwise
      direction of conduction, and other mechanisms of tachycardia, occur in some of
      the less typical forms of atrial fluter. Atrial fibrillation is caused by
      multiple wavelets which randomly conduct through the atrial myocardium and are
      responsible for the irregular 'fibrillation waves' on the ECG. Supraventricular
      tachycardia presents as a narrow complex tachycardia unless pre-existing or rate
      related bundle branch block is present. Less common causes for a broad complex
      tachycardia occurring in supraventricular tachycardia include an accessory
      atrioventricular or atriofascicular pathway conducting antegradely during
      tachycardia, or accessory pathway participation as a bystander during
      supraventricular tachycardia. ECG features which can help to distinguish between
      atrioventricular nodal re-entrant tachycardia and atrioventricular re-entrant
      tachycardia include: (1) the presence of a delta wave during sinus rhythm which
      is highly suggestive of atrioventricular re-entrant tachycardia as the mechanism
      of supraventricular tachycardia; (2) the finding of a pseudo s (lead II) or
      pseudo r' (lead V1) during tachycardia in atrioventricular nodal re-entrant
      tachycardia; (3) lengthening of the tachycardia cycle length in cases of
      atrioventricular re-entrant tachycardia when bundle branch block occurs
      ipsilateral to the accessory pathway and (4) the finding of QRS alternans during
      tachycardia which is suggestive of atrioventricular re-entrant tachycardia. "Long
      RP' tachycardia may be caused by an atrial tachycardia due to an inferiorly
      situated area of abnormal automaticity, atypical atrioventricular nodal re
      entrant tachycardia with slow retrograde conduction, or atrioventricular re
      entrant tachycardia with an accessory pathway conducting slowly from ventricle to
      atrium during tachycardia.

PMID- 9152670
TI  - Why does atrial fibrillation occur?
AB  - Atrial fibrillation is often associated with atrial enlargement and stretch is
      known to cause electrophysiological alterations. Acute stretch may, depending on
      the moment at which it is applied, cause action potential shortening or induce
      both early and delayed afterdepolarizations which, when large enough, may
      initiate triggered premature action potentials. The effects of acute stretch may
      be very different from those of chronic stretch. In fact, in dogs with mitral
      valve disease in which progressive atrial enlargement, leading to atrial
      fibrillation, developed over a period of years, hardly any changes in
      transmembrane potential characteristics were found. In contrast, marked fibrosis
      developed which could favour re-entry because of slow fragmented conduction. A
      number of electrophysiological changes have been found in isolated preparations
      from human atria that had been fibrillating. Action potentials had a shorter
      duration and a triangular configuration in contrast to action potentials from
      normal atria that mostly showed a distinct plateau. Refractory periods were also
      shorter and the normal rate adaptation of the refractory period disappeared, so
      that, following a slowing of the heart rate, the refractory period did not
      prolong. These changes largely seem to be the result of prolonged episodes of
      rapid atrial activity and may be called electrophysiological remodelling. In
      addition, a marked dispersion refractoriness has been found which might be due to
      different factors, such as fibrosis and local denervation. It is likely that
      atrial dilatation and fibrosis are important factors in the occurrence and
      maintenance of atrial fibrillation. In an enlarged atrium, multiple re-entrant
      circuits can co-exist. Fibrosis leads to inhomogeneities in both conduction and
      refractoriness. Finally, the arrhythmia itself causes persistent shortening of
      refractoriness. All of these changes favour re-entry.

PMID- 9152671
TI  - Treating the non-electrical risks of atrial fibrillation.
AB  - Atrial fibrillation is a common condition and carries a risk of thromboembolism.
      There is general acceptance that those patients with atrial fibrillation
      secondary to valvular (and in particular mitral) heart disease or following valve
      replacement require anticoagulation. Since patients with non-valvular causes of
      atrial fibrillation are a more heterogeneous group, the indications for
      anticoagulation have been less clear. A number of benchmark studies clearly
      indicate that the risk of stroke can be reduced by up to 70% in those treated
      with warfarin, but only by a variable 30% with aspirin. Problems with
      interpretation of the results of these studies relate to the younger age range
      included and a low recruitment rate, leading to a possible under-estimate of the
      bleeding risk. Subgroup analysis provides risk stratification for patients with
      non-valvular atrial fibrillation so that those with three or more of any of the
      five following risk factors: congestive heart failure, hypertension, previous
      stroke, left atrial enlargement or left ventricular hypertrophy, have an 18%
      chance of new thromboembolic events, whereas this falls to one third of this with
      only one or two risk factors, and 1% with none. Those with so-called lone atrial
      fibrillation aged < 60 years have a very low incidence of atrial fibrillation and
      can be considered for aspirin alone. The trials supporting in these statements
      are presented.

PMID- 9152672
TI  - Using the right drug: a treatment algorithm for regular supraventricular
      tachycardias.
AB  - Despite the recent advent of and the successful results from catheter ablation,
      pharmacological therapy is still used by most clinicians as the first line
      therapy in patients with regular supraventricular tachycardias. Before
      prescribing an antiarrhythmic agent, documentation of the arrhythmia using a 12
      lead electrocardiogram (ECG) is necessary to identify the type of tachycardia.
      The ECG diagnosis is based on the presence and polarity of the P wave, the P to
      QRS relationship, the presence of QRS alternation and the effect of bundle branch
      block on tachycardia rate. Most regular supraventricular tachycardias use the
      atrioventricular node either passively, as in atrial tachycardias or flutter, or
      actively, as paroxysmal junctional tachycardias. The Sicilian Gambit approach
      attempted to introduce some rationale in the choice of an antiarrhythmic agent,
      taking into account tachycardia mechanism, by defining the critical components of
      the tachycardia and the vulnerable parameter, i.e. the component that may readily
      be affected by an appropriate antiarrhythmic agent. For this approach, an
      electrophysiological study is particularly useful. The most common regular
      paroxysmal supraventricular tachycardias include atrioventricular nodal re
      entrant tachycardias and atrioventricular re-entrant tachycardias which use an
      overt or concealed accessory atrioventricular connection (Kent bundle) or
      atriofascicular connection (Mahaim). For acute termination of paroxysmal
      junctional tachycardia, intravenous adenosine is the drug of choice. For the
      prevention of the tachycardia attacks in atrioventricular nodal re-entrant
      tachycardia, the agents with a depressive effect on the antegrade slow pathway,
      such as calcium channel blockers or beta-blockers, are likely to be effective. If
      they fail, sodium channel blockers (propafenone or flecainide) may be indicated.
      In tachycardias involving accessory connections, agents that affect fast channel
      dependent tissue (propafenone, flecainide, cibenzoline, disopyramide or
      hydroquinidine) are effective. Potassium current blockers, such as sotalol or
      amiodarone, represent an alternative therapy. In atrial tachycardias, the use of
      propafenone, flecainide or sotalol constitute a logical choice. In drug-resistant
      cases, amiodarone is the most potent agent. Radiofrequency ablation of the slow
      atrioventricular nodal pathway, of an accessory connection or of an atrial focus,
      is indicated in drug-resistant or drug-intolerant patients and is increasingly
      offered as an alternative therapy.

PMID- 9152673
TI  - Using the right drug. A treatment algorithm for atrial fibrillation.
AB  - Atrial fibrillation is the commonest sustained cardiac arrhythmia. Its incidence
      increases with age and in association with organic heart disease, in particular
      valvular heart disease, left ventricular dysfunction and in association with
      thyrotoxicosis and alcohol excess. Atrial fibrillation may present as paroxysms
      of self-terminating arrhythmia or as a sustained arrhythmia. In the former
      instance, management is directed towards suppression of paroxysms and will
      commonly involve class 1C, class 2 or class 3 agents. If atrial fibrillation is
      sustained, a decision as to the desirability of cardioversion must be made. If
      this can be achieved successfully, particularly if the episode was of brief
      duration and associated with a reversible cause, sinus rhythm may be preserved
      without further antiarrhythmic therapy. Otherwise prophylactic therapy as used
      for paroxysmal atrial fibrillation is appropriate. In patients who fail to
      respond to cardioversion, or in those with advanced organic heart disease, long
      standing atrial fibrillation or marked dilatation of the left atrium in which
      case cardioversion is unlikely to be successful, the principal therapeutic
      strategy is to control ventricular rate. Classically, digoxin is used for this
      purpose. Additional agents which will slow the ventricular rates, such as beta
      blockers, amiodarone or calcium channel antagonists (verapamil or diltiazem), may
      be necessary if the ventricular rate remains uncontrolled and continues to
      produce severe symptoms. In the event of failure of medical therapy to control
      ventricular rate, atrioventricular nodal modification or ablation may be
      appropriate.

PMID- 9152674
TI  - Avoiding drug problems. The safety of drugs for supraventricular tachycardia.
AB  - To minimize drug problems in the treatment of supraventricular tachycardias, it
      is important to understand the spectrum of adverse events and to identify
      patients at high risk for these problems. Adverse cardiac and non-cardiac effects
      are associated, to varying degrees, with currently available antiarrhythmics.
      Cardiac adverse events include the development of rhythm disturbances, such as
      ventricular tachycardia or torsades des pointes, may result in syncope or death.
      In a meta-analysis of six randomized trials of quinidine vs placebo for atrial
      fibrillation, 1.8% of quinidine-treated patients died as opposed to 0.3% of
      placebo-treated patients. This increase in mortality was also noted in patients
      enrolled in the Stroke Prevention in Atrial Fibrillation Trial who were treated
      with type I antiarrhythmics. This increase in mortality was confined primarily to
      patients with a history of congestive heart failure. In a randomized trial of
      propafenone and sotalol for the treatment of atrial fibrillation, two out of 50
      patients receiving sotalol died suddenly, one of whom had hypokalaemia-associated
      torsades des pointes. No patient receiving propafenone died during this trial. In
      a meta-analysis of propafenone's effect in treating supraventricular
      tachyarrhythmias in over 3100 adult patients, overall mortality was extremely low
      at 0.3%. Structural heart disease may increase the risk of antiarrhythmic agents.
      During inpatient drug trials in patients treated for atrial fibrillation at
      Brigham and Women's Hospital, adverse cardiac events, primarily bradyarrhythmias,
      occurred in up to 15% of the patients. Older age and prior myocardial infarction
      were associated with an increased risk of adverse events. Adverse drug problems
      may be minimized by careful attention to electrolytes, medications, concomitant
      medical illnesses, and underlying conduction disease. Careful monitoring of
      patients during initiation of therapy, especially those patients with ischaemic
      heart disease, congestive heart failure, and who are older, may minimize drug
      related problems.

PMID- 9152675
TI  - Management of atrial fibrillation in the setting of heart failure.
AB  - Heart failure is often complicated by atrial fibrillation. Once atrial
      fibrillation has started it further enhances heart failure due to uncontrolled
      rate with shortened filling time and provocation of tachycardiomyopathy. Absent
      atrial kick and irregularity of the ventricular rhythm also contribute.
      Considering these mechanisms, restoration of sinus rhythm is most beneficial but
      is associated with frequent recurrences. Before cardioversion heart failure must
      be treated. ACE inhibition, initiated before cardioversion, may enhance
      maintenance of sinus rhythm by reducing neurohumoral activation. As a
      consequence, arrhythmogenic factors diminish and ventricular function may
      improve. beta-blockade and amiodarone may have similar effects. If cardioversion
      fails, adequate rate control is mandatory to prevent progressive ventricular
      dysfunction. Digitalis is the treatment of first choice, but when the heart rate
      remains uncontrolled low-dose beta-blockade should be given. If the ventricular
      rate remains uncontrolled despite drugs, atrioventricular node ablation with
      implantation of a pacemaker may be considered. Not only patients with idiopathic
      heart failure and atrial fibrillation, but also those with significant underlying
      heart disease may benefit from this intervention. In atrial fibrillation patients
      undergoing cardiac surgery for heart failure due to valvular disease, additional
      arrhythmia surgery may be contemplated.

PMID- 9152676
TI  - Supraventricular tachycardia. Doing the right things.
AB  - Supraventricular tachycardia is an outmoded term which, while widely used, is
      imprecise and is impeding the development of antiarrhythmic management
      strategies. Precise arrhythmia descriptions, recognition of the arrhythmogenic
      basis of the arrhythmia and an appreciation of the variety of therapeutic
      approaches available is an essential part of modern day medicine. The selected
      strategy will be dictated by an accurate assessment of how the arrhythmia
      disadvantages the patient. Good clinical practice will ensure constant monitoring
      of the effect of and need for therapy. The 'right things' in arrhythmia
      management can now be defined and should form the basis of new, practical,
      clinical protocols.

PMID- 9152677
TI  - Nutritional survey in Greek children: nutrient intake.
AB  - The aim of the survey was to record the food habits and nutrient intake of Greek
      children. Data was obtained by a 3 d household measured diet record from a random
      stratified sample (1936 children aged 2-14 y). Mean daily protein intake was much
      higher than PRI and none of the children had lower intake than AR. Mean energy
      intake from protein was 15%, carbohydrate 44% and fat 41%. Eighty-four percent of
      children had energy intake from fat higher than the AR. Saturated fatty acids
      (SFA) provided approximately 15%, monounsaturated (MUFA) 17% and polyunsaturated
      (PUFA) 6% of energy. Eighty-seven percent of children had higher intake of SFA
      than the AR. Six percent of children had SFA intake lower than the AR and 50%
      higher than the AR. None of the children had PUFA intake lower than PRI and 0.3%
      higher than the maximum limit. 4.2% of children had calcium intake lower than LTI
      and 88% higher or equal to PRI. All children had phosphorus intake higher than
      PRI and less than the lower safe ratio of Ca/P; 50% of them had P intake higher
      than 1.5 g/d. The majority of children had sufficient iron intake with the
      exception of menstruated girls. Mean vitamin A intake was higher than PRI and
      lower than the toxic levels. All children had vitamin C intake higher than LTI.
      Median vitamin D intake varied from 1.7-2.1 micrograms. Median energy intake was
      higher than the AR in preschool children, but lower in the older children. We
      conclude that Greek children do not underintake energy and protein, overintake
      SFA, have safe intake of PUFA, vitamin A and C and high intake of MUFA,
      underintake carbohydrates, have adequate Ca, but a considerably high P intake.
      Vitamin D is low in small children, but the biological available vitamin D is
      obviously higher due to sunlight.

PMID- 9152678
TI  - Fuzzy sets and fuzzy decision making in nutrition.
AB  - OBJECTIVE: This paper demonstrates that a nutrient intake can be described in a
      differentiated way and can be evaluated by employing fuzzy decision making. It
      also examines whether fuzzy decision making can simplify nutrition education by
      small individual improvements in food selection behaviour. RESULTS: The
      recommendations for nutrient intakes are presented as fuzzy sets, so that the
      intake of each nutrient can be evaluated by an objective fuzzy value. The
      evaluation of the harmonic minimum allows, for the first time, that the fuzzy
      value of an individual nutrient can be stated as a total value. On the basis of
      individual nutrition assessment, fuzzy logic in connection with fuzzy decision
      making, allows optimization of meals considering individual food preferences.
      This makes it possible in nutrition counselling to improve the nutrient intake
      markedly with relative small changes in food choice. CONCLUSION: Fuzzy decision
      making can simplify and optimize nutrition education.

PMID- 9152679
TI  - Increasing prevalence of underreporting does not necessarily distort dietary
      surveys.
AB  - OBJECTIVES: To study the magnitude of and trends in energy underreporting and to
      compare food consumption, nutrient intake and socioeconomic characteristics of
      underreporters to those of other Finnish adults. DESIGN: Cardiovascular risk
      factor surveys in 1982 and 1992 using a 3 d food record. Underreporting was
      defined as energy intake lower than 1.27* BMR, since energy intake < 1.27* BMR is
      improbable. SETTING: Four areas in Finland, both rural and urban. SUBJECTS: 1746
      men and 1921 women, aged, 25-64 y. RESULTS: Proportion of underreporters has
      increased from 33% in 1982 to 46% in 1992 among women and from 27% in 1982 to 42%
      in 1992 among men. In a logistic regression model, BMI over 25 kg/m2, female
      gender, age over 45 y and high educational level predicted underreporting. Shares
      of energy intake from fat, carbohydrates, protein and alcohol remained the same
      whether or not underreporters were excluded. However, underreporters consumed
      significantly higher proportion of vegetables, fish, meat, potatoes, fruit and
      berries and less fat than others. In the 1992 data the absolute intake of most
      micronutrients increased and micronutrient densities decreased when
      underreporters were excluded. CONCLUSIONS: The proportion of underreporters has
      grown from 1982 to 1992. Results expressed as a percentage of energy intake are
      not affected by the exclusion of underreporters. In contrast, micronutrient
      intakes, both absolute and energy density values, were distorted by
      underreporting. Underreporting should be taken into account in future studies.

PMID- 9152680
TI  - Impact of a single megadose of vitamin A at delivery on breastmilk of mothers and
      morbidity of their infants.
AB  - OBJECTIVES: To evaluate the effect of vitamin A supplementation 24 h after
      delivery on breastmilk retinol concentration. METHODS: Fifty low income women
      were randomly assigned to a single oral dose of 209 micromol of Vitamin A or none
      at delivery. Maternal serum and breastmilk retinol levels and infant morbidity
      and anthropometry were serially assessed. RESULTS: Mean (95% CI) serum retinol
      levels increased in the supplemented mothers at 2.77 (2.3, 3.2) compared to 1.15
      (0.9, 1.4) micromol/l in controls (P < 0.05) and remained at a significantly
      higher level of 1.59 (1.4, 1.8) micromol/l compared to 1.33 (1.8, 1.5) micromol/l
      in the control group (P < 0.001) up to a period of three months. Breastmilk
      retinol concentration was also greater at 24 h after supplementation, mean (CI)
      11.34 (9.0, 13.7) micromol/l, compared to 2.95 (2.3, 3.6) micromol/l in the
      control group (P < 0.0001), and remained higher for the next six months at 1.06
      (0.9, , 1.3) micromol/l compared to 0.73 (0.6, 0.8) micromol/l in the control
      group (P < 0.02). Infants of the supplemented mothers had reduced mean duration
      of respiratory tract infection of 3.1 (2.7, 3.5) days compared to 3.7 (3.3, 4.2)
      days (P < 0.03) and mean incidence of febrile illness 0.1 (0.1, 0.1) compared to
      control infants 0.3 (0.3, 0.3) days, (P < 0.002). CONCLUSION: Vitamin A
      supplementation of malnourished mothers maintains higher breastmilk retinol
      concentration for at least six months and reduces the duration of respiratory
      tract infection and febrile illness in their breastfed infants.

PMID- 9152681
TI  - Whole-body protein turnover in humans fed a soy protein-rich vegetable diet.
AB  - OBJECTIVES: This study was designed to compare the whole-body protein turnover in
      humans after the ingestion of a soy protein-rich vegetable diet with that of a
      control group fed a western animal protein-rich diet. SUBJECTS: Twelve male
      volunteers were divided into two groups of six subjects who were given for two
      weeks either a 85% vegetable protein diet (diet VP) or a control western animal
      protein-rich diet (diet AP). INTERVENTIONS: Whole-body protein turnover was
      estimated at the end of the two-week controlled diet period using the [15N]
      glycine end-product method. Nitrogen flux rates were determined in the fed state
      (1.3 g protein/kg) over a 9 h period after the dose of [15N]-glycine was given.
      RESULTS: After the 9 h of the test, the urinary ammonia excretion was
      significantly higher in the group receiving the diet AP than that in the group
      receiving the diet VP (P < 0.05). In contrast, there was no significant
      difference for both total nitrogen and urea nitrogen excretions. Both the protein
      synthesis and the protein breakdown were similar in both groups. In the same way,
      the net protein deposition measured in the fed state during 9 h was similar for
      both diets at 0.07 g/kg/h. CONCLUSIONS: Young adults fed 1.3 g/kg/d of either
      meat or vegetable protein-rich diet for two weeks did not show a different
      protein turnover.

PMID- 9152682
TI  - A multi-center comparison of dual energy X-ray absorptiometers: in vivo and in
      vitro soft tissue measurement.
AB  - OBJECTIVE: To assess intra- and inter-site soft tissue variability by dual energy
      X-ray absorptiometry (DXA). DESIGN: Cross-sectional trial. SETTING: Three medical
      research institutions. SUBJECTS: Five humans (in vivo) and four phantoms (in
      vitro), configured from two whole body phantoms with artificial skeletons and
      thickness overlays. INTERVENTIONS: Duplicate total-body DXA scans were performed
      on all subjects at each institution within a 15 d period. RESULTS: All intra-site
      coefficients of variation (CV) were < 0.5% for total tissue mass, but in vitro
      and in vivo Cvs were 7.2% and 2.3% for fat mass (FM) and 2.5% and 0.9% for lean
      mass (LM), respectively. Several total-body and regional FM and LM measurements
      were significantly different between sites (P < 0.05), with percent differences
      between sites ranging from 2.6-13.3% for FM and from 1.6-13.6% for LM. Site 2 was
      consistently lower for FM and Site 3 was consistently lower for LM. CONCLUSIONS:
      These results stress the need for both rigorous and standardized cross
      calibration procedures for soft tissue measurement by DXA.

PMID- 9152683
TI  - Enhanced plasma level of lipid peroxidation in Iranians could be improved by
      antioxidants supplementation.
AB  - OBJECTIVE: To study the influence of supplementation with antioxidants on
      factors, which might increase the risk of coronary heart disease (CHD) in
      Iranians. DESIGN: Twenty-one male volunteers enter the prospective, single-blind,
      randomized study. SETTING: The supplementation was conducted at the
      Cardiovascular Center, University of Tehran, the biochemical analysis were
      carried out in the University of Graz. SUBJECTS: Twenty-one male medical students
      were recruited by advertisement. Five subjects were dropped out due to lack of
      the compliance. METHODS: One group of Iranians received 30 mg/d beta-carotene and
      placebo for alpha-tocopherol; the other received beta-carotene plus 400 IU alpha
      tocopherol for ten weeks. Concentrations of antioxidants in plasma and low
      density lipoproteins (LDL), plasma lipid profile, autoantibody against oxidized
      LDL (oLAb) and malondialdehyde (MDA) concentrations in plasma were measured.
      Oxidative resistance of LDL was estimated using conjugated diene assay. RESULTS:
      Iranians had a significantly lower plasma levels of total cholesterol (P <
      0.002), LDL-cholesterol (P < 0.01) and high density lipoprotein-cholesterol (P <
      0.002), compared to healthy Austrian subjects (n = 13). Although the baseline
      concentrations of alpha-tocopherol and beta-carotene were comparable with
      Austrians, lycopene, canthaxanthin and lutein were significantly higher in
      Iranians (P < 0.03-0.001). In vitro oxidative resistance of LDL, measured as lag
      time, was slightly higher (P < 0.01) in Iranians comparing with Austrians. Plasma
      MDA and oLAb concentrations were significantly higher in Iranians (P < 0.001).
      Both dietary supplementations reduced plasma MDA concentrations (P < 0.001
      0.001). A key finding was that a supplement combined with alpha-tocopherol caused
      also a significant increase of oLAb concentration (P > 0.01) as well as the
      significant increase of lag-time (P > 0.005). CONCLUSIONS: This study shows that
      high plasma MDA level of Iranians can be decreased by beta-carotene
      supplementation with or without alpha-tocopherol. However, alpha-tocopherol is a
      more powerful antioxidant, which can increase the resistance of LDL to oxidation,
      reduce the MDA concentrations in plasma and increase autoantibodies to oLDL.

PMID- 9152684
TI  - Alcohol beverage drinking, diet and body mass index in a cross-sectional survey.
AB  - OBJECTIVE: The study was carried out to determine the associations of alcohol
      beverage drinking with macronutrients, antioxidants, and body mass index.
      SETTING: Dietary subsample of the 1992 Finmonica cardiovascular risk factor
      survey in Finland; a cross-sectional study. SUBJECTS: 985 women and 863 men were
      drawn from the population register in the four monitoring areas. All subjects
      were 25-64 y of age. METHODS: The mailed questionnaire included questions
      covering socioeconomic factors, physical activity, smoking, and alcohol
      consumption. The diet was assessed using a three-day food record. RESULTS: The
      dietary differences between abstainers and alcohol consumers were more
      significant than between consumers of different alcoholic beverages. Among
      drinkers, fat intake as a percentage of energy was higher and carbohydrate intake
      was lower than among abstainers. Those who preferred wine, however, had the
      highest vitamin C intake; female wine drinkers also had the highest carotenoid
      intake. With the exception of those who mainly preferred spirits, alcohol energy
      was not added to the diet but seemed to substitute food items both in men and
      women. Despite the similar total daily energy intakes, daily energy expenditure,
      and physical activity index, male drinkers were leaner than abstainers. In women,
      the proportion of underreporters of energy intake increased with increasing
      alcohol consumption, and the association between alcohol and body mass index was
      similar to that in men after the exclusion of underreporters. CONCLUSIONS:
      Alcohol consumers were leaner than abstainers, and wine drinkers in particular
      had more antioxidants in their diet.

PMID- 9152685
TI  - The validity of predicting the basal metabolic rate of young Australian men and
      women.
AB  - OBJECTIVES: To assess the accuracy of the Schofield, Schofield & James (1985)
      equations and those of Hayter & Henry (1994) for the prediction of the basal
      metabolic rate (BMR), of young Australians. DESIGN: BMR was measured by indirect
      calorimetry, while fat free mass (FFM) and fat mass (FM) were measured by
      bioelectric impendence analysis (BIA) in 128 volunteers (39 men and 89 women),
      aged between 18 and 30 y. SETTING: Deakin Institute of Human Nutrition, Deakin
      University, Melbourne, Australia. RESULTS: The measured BMR of Australian men and
      women were significantly lower (P < or = 0.001) than the predicted BMR using the
      Schofield et al (1985) equation, with a mean (s.d.) bias (bias = measured -
      predicted BMR) of -406(513) kj/d in men and -124(348) kj/d in women. The measured
      BMR of Australian men and women were similar to the predicted BMR using the
      equations of Hayter & Henry (1994) and bias was unrelated to body weight. BMR
      adjusted for FFM and FM was significantly higher by three percent in women on
      oral contraceptive agents (OCA) as compared to those not on OCA. CONCLUSIONS: The
      Schofield et al (1985) equations are not valid for the prediction of BMR of young
      Australian men and women. The equations of Hayter & Henry (1994) for North
      Europeans and Americans, provide an accurate estimate of the BMR of Australian
      men and women at the group level. However, in young women not using OCA a
      correction factor of 0.97 applied to the predicted BMR provides a better
      estimate.

PMID- 9152686
TI  - Could a satellite-based navigation system (GPS) be used to assess the physical
      activity of individuals on earth?
AB  - OBJECTIVES: To test whether the Global Positioning System (GPS) could be
      potentially useful to assess the velocity of walking and running in humans.
      SUBJECT: A young man was equipped with a GPS receptor while walking running and
      cycling at various velocity on an athletic track. The speed of displacement
      assessed by GPS, was compared to that directly measured by chronometry (76
      tests). RESULTS: In walking and running conditions (from 2-20 km/h) as well as
      cycling conditions (from 20-40 km/h), there was a significant relationship
      between the speed assessed by GPS and that actually measured (r = 0.99, P <
      0.0001) with little bias in the prediction of velocity. The overall error of
      prediction (s.d. of difference) averaged +/-0.8 km/h. CONCLUSION: The GPS
      technique appears very promising for speed assessment although the relative
      accuracy at walking speed is still insufficient for research purposes. It may be
      improved by using differential GPS measurement.

PMID- 9152687
TI  - Minimally invasive therapy in diagnosis and treatment of spontaneous
      haematopneumothorax.

PMID- 9152688
TI  - Plasma lipoperoxidative markers in ischaemic stroke suggest brain embolism.
AB  - Plasma activity of myeloperoxidase (MPO), malondialdehyde (MDA) and 4
      hydroxynonenal (HNE) was measured prior to any treatment in 50 consecutive stroke
      patients with acute cerebral ischaemia, as well as in 14 healthy control
      subjects. Mann-Whitney-Wilcoxon test for unpaired data showed greater values of
      MPO (p < 0.01), MDA (p < 0.01) and HNE (p < 0.05) in stroke patients compared
      with controls. Considering as covariates the level of consciousness (GCS < 9 vs >
      or = 9), possible sources of emboli (yes vs no), leukocyte count (< 10 x 10(9)/1
      vs > or = 10 x 10(9)/1) and relevant comorbid diseases (yes vs no), exact
      multiple logistic regression analysis indicated that only the presence of
      possible cardiac sources of emboli was associated with changes in by-products of
      lipid peroxidation. If confirmed in a larger series of subjects, our results
      could have therapeutic implications, providing more support for the use of free
      radical scavengers in the acute care of stroke patients with a possible
      cardioembolic aetiology.

PMID- 9152689
TI  - The impact of advanced trauma life support course on graduates with a non
      surgical medical background.
AB  - The aim of this study was to assess advanced trauma life support (ATLS) and
      combat trauma life support (CTLS) skills implementation among general practising
      physicians, its perceived utility in their routine daily practice as well as in
      their potential army combat assignments. One hundred and ten physicians,
      graduates of ATLS and CTLS courses, from the subspecialties of geriatrics,
      psychiatry and family medicine, were surveyed by telephone, to answer a specially
      designed questionnaire. The response rate was 82%. Professional distribution was:
      6.6% geriatrics; 46.7% family physicians; and 46.7% psychaitrists. The number of
      trauma events treated by these physicians in their post-course practise was:
      geriatrics-three; family physicians-30; psychiatrists-18. We believe that a
      properly designed ATLS course, executed and applied to general practitioners, can
      be highly beneficial to trauma victims.

PMID- 9152690
TI  - Prophylactic, empiric and therapeutic use of antibiotics. Do we need a guide: a
      universal edition or a local one?
AB  - The goal of the antibiotic policy in hospitals is a correct and restrictive use
      of antimicrobial agents. Guidelines on antibiotic use aim to improve the quality
      of care, to reduce costs and to prevent the emergence of (multi-)resistant
      microorganisms. Strategic options and methods to reach these objectives are
      published by consensus committees of scientific societies and health care
      organizations. The local guidelines must be based upon the universal principles
      of prophylactic, empiric and therapeutic use of antimicrobial agents but they
      also take into account the local epidemiology of infectious diseases,
      microbiology and resistance patterns as well as the local clinical experience.
      Our experience on how an antibiotic policy was developed and implemented in our
      large university hospital is described.

PMID- 9152691
TI  - The emergency department in a 2000-bed teaching hospital: saving open ward and
      intensive care facilities.
AB  - Providing emergency medicine at the entrance to the hospital proves to be a
      sufficient link between pre- and inhospital medical care. The aim of our study is
      to investigate how many open ward and intensive care facilities can be saved
      within the hospital by the emergency department. Therefore, the data of our
      emergency department within a 2000-bed teaching hospital are retrospectively
      analysed. Unstable life-threatening emergencies for acute care, stable for
      immediate care and non-life-threatening emergencies are defined. Patients were
      discharged, admitted to an open ward, intensive care unit, the operation theatre
      or died. According to the level of care needed in the emergency department the
      continuing medical management is investigated. Over a 2-year period, 102,411
      patients entered our emergency department. Overall 1498 (1%) needed acute care,
      3652 (4%) immediate care and 97,261 (95%) delayed care. Of the acute care
      patients, 29 (2%) were discharged, 573 (38%) were admitted to an open ward, 551
      (37%) to an intensive care unit, 67 (4%) needed surgery and 278 (19%) died. Of
      the immediate care patients, 1611 (44%) were discharged, 1755 (48%) were admitted
      to an open ward, 551 (37%) to an intensive care unit, and 286 (8%) needed
      surgery. Of the delayed care patients, 93061 (96%) were discharged and 4200 (4%)
      were admitted to an open ward. Of 5150 patients with life-threatening diseases,
      551 (11%) needed an intensive care unit and 2328 (45%) an open ward. Providing
      acute and immediate care in our emergency department saves both intensive care
      and open ward facilities of the hospital.

PMID- 9152692
TI  - Twenty-four hour nurse practitioner service in the accident and emergency
      department.
AB  - This paper discusses the introduction of a 24-h nurse practitioner service in a
      major accident and emergency department and monitors it over a 3-month period.
      The paper provides a description of the activities of the nurse practitioners and
      a critical evaluation of their role. It shows that every major accident and
      emergency department can set up a 24-h nurse practitioner scheme and the
      organization of such a scheme can be very simple. This is the first article to
      look at a 24-h service.

PMID- 9152693
TI  - The myocardium and brain SPECT findings in organophosphate poisoning.
AB  - A case of organophosphate poisoning is presented by using Tc-99m HMPAO
      (hexamethyl propylenamine oxime) brain SPECT (single photon emission computer
      tomography) and Tc-99m Sestamibi myocardial SPECT findings in the acute recovery
      and delayed phases. On the 4th day, brain SPECT imaging showed the perfusion
      defects in the left parietal lobe of the brain. On the 5th day myocardium
      scintigraphy also revealed the anterolateral wall perfusion defect. The
      myocardial defect became more prominent but brain defect was smaller than before,
      on the 19th day of the therapy. Two months later, on the third examinations of
      the brain and myocardium, their imagings were both normal.

PMID- 9152694
TI  - Basilar migraine.
AB  - Basilar migraine is a complicated headache which the International Headache
      Society describes as 'migraine with aura symptoms clearly originating from the
      brainstem or from both occipital lobes'. For years this headache was thought to
      originate from a transient disturbance in the vertebrobasilar circulation, but
      more recent studies suggest that a central neuronal disorder may be the source of
      migraine. Basilar migraines may have certain symptoms which are similar to other
      neurologic, vascular, psychiatric and metabolic diseases, yet there are specific
      criteria which can help differentiate it from other diagnoses. It is
      characterized by a throbbing occipital headache which may be preceded by an aura.
      The unusual symptoms of basilar migraine, which may precede and continue
      throughout the duration of the headache and even after it, include bilateral
      visual symptoms, altered mental status, vertigo, gait ataxia, bilateral
      paresthesia, bilateral paralysis and dysarthria. We describe a 29-year-old black
      female whose husband brought her to the emergency department complaining of
      confusion, headache, and left-sided weakness for 2 h prior to arrival.

PMID- 9152695
TI  - Traumatic radial head dislocation in children--a missed injury.
AB  - The purpose of this article is to remind accident and emergency doctors of an
      easily missed injury-isolated traumatic radial head dislocation in children. We
      present two such cases. This is a very uncommon injury and the diagnosis was
      overlooked in both cases. A high index of suspicion is necessary and careful
      examination of the radiographs is mandatory. The radiographic appearance of this
      injury is explained.

PMID- 9152696
TI  - Nasal packing for epistaxis: two methods compared.

PMID- 9152697
TI  - Mood and symptom reporting among middle-aged women: the relationship between
      menopausal status, hormone replacement therapy, and exercise participation.
AB  - Vasomotor, somatic, and psychological symptoms associated with menopause are
      often treated with hormone replacement therapy (HRT), but the role of
      nonpharmacological interventions has received little attention. Two studies used
      the Profile of Mood States (POMS) and Women's Health Questionnaire (WHQ) to
      examine the effects of exercise among 4 groups of Australian women:
      premenopausal, perimenopausal, postmenopausal without HRT, and postmenopausal
      with HRT. Study 1, a comparison of exercisers and nonexercisers, showed that
      exercisers' moods were significantly more positive than sedentary women's moods,
      regardless of menopausal state. Exercising women also scored lower on somatic
      symptoms and memory-concentration difficulties. Study 2 examined the acute
      effects of aerobic exercise (premenopausal, postmenopausal without HRT, and
      postmenopausal with HRT) and found significant enhancements in mood and
      reductions in reported somatic and vasomotor symptoms immediately following an
      aerobic class. Exercise may assist in the alleviation of some menopausal
      symptoms.

PMID- 9152698
TI  - Sleep and the menstrual cycle.
AB  - To evaluate changes in sleep across the phases of the menstrual cycle, sleep-wake
      diaries were completed by 32 healthy women twice daily for 2 menstrual cycles.
      There was a significant increase in sleep onset latency and a significant
      decrease in sleep efficiency and sleep quality during the luteal phase. This
      increase in sleep disturbance was observed in the entire sample and was not
      related to the severity of other premenstrual symptoms. However, women having
      increased severity of other premenstrual symptoms reported greater luteal
      increase in daytime sleepiness. Thus, although menstruating women are likely to
      show increased sleep disturbance during the luteal phase, those with other, more
      severe premenstrual symptoms are more likely to experience a luteal increase in
      daytime sleepiness.

PMID- 9152699
TI  - Are two interventions worse than none? Joint primary and secondary prevention of
      eating disorders in college females.
AB  - Prevention programs for eating disorders attempt to simultaneously prevent new
      cases from arising (primary prevention) and encourage students who already have
      symptoms to seek early treatment (secondary prevention), even though ideal
      strategies for these 2 types of prevention may be incompatible with each other.
      In the present study, an eating disorder prevention program was evaluated in a
      simple of female college freshmen. In the intervention, classmates who had
      recovered from eating disorders described their experiences and provided
      information about eating disorders. At follow-up, intervention participants had
      slightly more symptoms of eating disorders than did controls. The program may
      have been ineffective in preventing eating disorders because by reducing the
      stigma of these disorders (to encourage students with problems to seek help), the
      program may have inadvertently normalized them.

PMID- 9152700
TI  - Body image in obese women before, during, and after weight loss treatment.
AB  - Body image, as measured by the Appearance Evaluation and Body Areas Satisfaction
      scales of the Multidimensional Body-Self Relations Questionnaire (T.F. Cash,
      1994b), was assessed in 59 obese women before, during, and after 48 weeks of
      weight loss treatment. Before treatment, positive ratings of body image were
      associated with higher levels of self-esteem, lower levels of dysphoria, and
      fewer previous diets. After 24 weeks and a mean weight loss of 19.4 kg (SD =
      6.5), participants showed significant (p < .0001) improvements in body image. A
      small weight gain from Week 24 to Week 48 was associated with a slight but
      significant worsening in both measures of body image. Nevertheless, after 48
      weeks and a mean weight loss of 16.3 kg (SD = 7.1), body image was significantly
      improved from baseline (p < .0001). Changes in body image were not related to
      changes in weight. Future studies are needed to separate the effects of treatment
      and weight loss on body image in obese persons.

PMID- 9152701
TI  - Correlates of change in depressive symptomatology among gay men with AIDS.
AB  - Longitudinal data from a sample of gay men living with AIDS (N = 128) were used
      to assess the relationship of change in various individual and situational
      correlates with change in depression. Results of regression analyses suggest that
      changes in physical symptomatology, in the number of bed days, and in the
      perceived sufficiency of social support are significantly correlated with
      concurrent change in depressive symptomatology. There was no evidence of change
      in the perceived sufficiency of social support buffering or amplifying the
      relationship of change in physical symptomatology with change in depression. The
      findings illustrate the need for the use of panel data (i.e., repeated
      assessments of the same individuals) and the assessment of change in both
      distress and its correlates among individuals living with AIDS.

PMID- 9152702
TI  - Relationship of job strain to standard coronary risk factors and psychological
      characteristics in women and men of the Family Heart Study.
AB  - This study reports on standard coronary risk factors (plasma lipids and
      lipoproteins, blood pressure, heart rate, age, body mass index) and psychosocial
      variables (job strain, Type A behavior, hostility, illnesses, medical and
      psychological symptoms, health-damaging behavior) in a community sample of 324
      employed men, 203 employed women, and 155 female homemakers. Employed women
      reported less hostility and fewer illnesses than homemakers and had lower
      cholesterol levels than homemakers and men. Job characteristics were unrelated to
      standard coronary risk factor levels in both sexes, but predicted medical
      symptoms and health-damaging behavior in men. These findings suggest that
      employment is associated with enhanced medical and physical well-being among
      women and point to possible behavioral and psychological pathways by which job
      strain may adversely influence men's health.

PMID- 9152703
TI  - Coping self-efficacy buffers psychological and physiological disturbances in HIV
      infected men following a natural disaster.
AB  - The importance of coping self-efficacy (CSE) appraisals on psychological and
      physiological functioning for HIV seropositive patients facing a severe
      environmental stressor was tested comparing 37 HIV-infected gay men and 42
      healthy male control participants following Hurricane Andrew. Results suggested
      that greater levels of CSE were related to lower emotional distress and
      posttraumatic stress disorder (PTSD) symptoms in both groups. In addition,
      greater CSE was associated with lower norepinephrine to cortisol ratios in the
      HIV group but not in the healthy control group. Results are discussed in relation
      to the coping process for HIV-infected individuals specifically and chronically
      ill populations in general who face severe environmental stressors.

PMID- 9152704
TI  - Monitoring attentional style and medical regimen adherence in hemodialysis
      patients.
AB  - Previous research involving individuals facing chronic health problems suggests
      that an attentional style characterized by pronounced monitoring of threat
      relevant information is associated with poorer behavioral and emotional
      adjustment. This study examined the hypothesis that a pronounced monitoring style
      would be associated with poorer medical regimen adherence in a sample of 51
      chronic hemodialysis patients. Hierarchical regression analyses (controlling for
      demographic factors and trait anxiety) revealed that "high monitors" exhibited
      higher interdialysis weight gains and higher serum K values reflecting poorer
      adherence to fluid-intake and dietary restrictions. However, monitoring was not
      associated with a measure of medication adherence. Partial support was found for
      a model suggesting that a lack of perceived control is responsible for the
      relationship between higher monitoring and poorer adherence.

PMID- 9152705
TI  - The development of an empirical psychosocial taxonomy for patients with diabetes.
AB  - The main purpose of this study was to develop and to cross-validate an
      empirically derived psychosocial taxonomy of patients with diabetes. In the first
      study, 101 patients with Type I or Type II diabetes completed the
      Multidimensional Diabetes Questionnaire. Cluster analysis identified three
      clusters, labeled adaptive copers, low support-low involvement, and spousal
      overinvolvement. In the second study, the taxonomy was cross-validated using an
      independent sample of 132 patients with long-standing Type II diabetes. The
      results confirmed that the multivariate classification system was unique and
      highly accurate. External validation, using general psychological as well as
      diabetes-specific measures, supported the validity and distinctiveness of the
      patients' profiles. These findings help establish a multiaxial psychosocial
      taxonomy of diabetes and may have significant implications for the management of
      patients with diabetes.

PMID- 9152706
TI  - Social-cognitive predictors of fruit and vegetable intake in children.
AB  - Social-cognitive theory (SCT) was used to explain the fruit and vegetable intake
      of 1,398 3rd graders. SCT variables assessed included self-efficacy, outcome
      expectations, preferences, social norms, asking skills, and knowledge. Fruit and
      vegetable intake was assessed with 7-day records. Bivariate correlations with
      fruit and vegetable intake ranged from .17 for asking skills to .29 for fruit and
      vegetable preferences. In analyses controlling for school-level clustering, only
      preferences and positive outcome expectations remained significantly associated
      with fruit and vegetable intake, accounting for approximately 10%-11% of the
      variance. Limitations in the conceptualization, scope, and measurement of the
      variables assessed may have contributed to the weak associations observed. Models
      incorporating factors other than individual-level social-cognitive variables may
      be required to more fully explain children's dietary behavior.

PMID- 9152707
TI  - Perceived benefits of and barriers to exercise and stage of exercise adoption in
      young adults.
AB  - College students (N = 432) completed questionnaires assessing current exercise
      participation, intention to become more active, perceived benefits of exercise,
      and perceived barriers to exercise. Confirmatory factor analyses of the benefit
      and barrier items suggested that a model containing 4 benefit factors (social,
      psychological, body image, and health) and 4 barrier factors (time-effort,
      social, physical effects, and specific obstacles) fit better than other models
      with fewer factors. Subscales derived from these factors revealed specific
      differences across participants who were categorized into 1 of 4 stages of
      exercise adoption. These findings confirm the multidimensional nature of
      perceived benefits of and barriers to exercise. Implications for the promotion
      and maintenance of exercise are discussed.

PMID- 9152708
TI  - Psychosocial outcomes of breast-conserving surgery versus mastectomy: a meta
      analytic review.
AB  - Effective breast-conserving surgical techniques for early-stage disease were
      developed to improve breast cancer patients' quality of life. The literature
      comparing the psychosocial sequelae of these newer treatments with mastectomy is
      ambiguous and shows an unexpected lack of substantial benefits. To clarify these
      inconsistencies, meta-analytic methods were used to summarize the findings of 40
      investigations. Mean weighted effect sizes were calculated for 6 psychosocial
      outcomes. Modest advantages for breast-conserving surgery were identified for
      psychological, marital-sexual, and social adjustment; body/self-image; and cancer
      related fears and concerns. Method of assignment to treatment and timing of
      assessment were relevant for some outcomes.

PMID- 9152709
TI  - Ethical hazards of the substituted judgement test in decision making concerning
      the end of life of dementia patients.

PMID- 9152710
TI  - The reliability and validity of the collateral source version of the Geriatric
      Depression Rating Scale administered by telephone.
AB  - OBJECTIVE: To prospectively evaluate the reliability and validity of the
      Collateral Source Geriatric Depression Scale (CS-GDS) administered by telephone
      (T-CS-GDS) in patients undergoing outpatient comprehensive geriatric assessment.
      SUBJECTS: Eighty-three geriatric patients evaluated in a 1-year period at the
      outpatient Geriatric Assessment Center of the University of Nebraska Medical
      Center. METHODS: The 30-item CS-GDS was completed by the collateral source of all
      patients on three occasions: by telephone several days before their assessment,
      face-to-face during their assessment visit and several days later, again by
      phone. During their assessment, all patients were evaluated by one of three
      geriatric psychiatrists who were blinded to CS-GDS results. The test retest
      reliability of the T-CS-GDS was measured by comparing the results of the two
      phone interviews. The construct validity of the T-CS-GDS was estimated by
      comparing the results of the initial T-CS-GDS with the CS-GDS obtained during the
      comprehensive assessment. The criterion validity of the T-CS-GDS was estimated by
      comparing the results of the T-CS-GDS with the clinical diagnosis of depression
      assigned by the psychiatrists. RESULTS: The individual items of the initial T-CS
      GDS showed substantial concordance with the second T-CS-GDS (kappa range 0.41
      0.8, mean = 0.61) and with the assessment GDS (kappa range 0.33-0.85, mean =
      0.61). Twelve items showed evidence of bias when comparing the two T-CS-GDSs and
      four items when comparing the initial T-CS-GDS with the CS-GDS done during the
      assessment. The mean number of symptomatic responses was not significantly
      different for the T-CS-GDS vs assessment administration but did decline slightly
      when comparing the two T-CS-GDSs. ROC curve analysis showed good agreement
      between the clinical diagnosis and the T-CS-GDS. CONCLUSION: The CS-GDS appears
      to maintain its reliability and validity when administered via telephone and thus
      may be useful for a variety of epidemiologic and clinical purposes.

PMID- 9152711
TI  - A case-control study of smoking and Alzheimer's disease.
AB  - OBJECTIVES: To study the association between Alzheimer's disease and smoking
      history. DESIGN: An unmatched case-control study. SETTING: Psychogeriatric unit
      serving an elderly population of Warrington. PERIOD: 2 years 1991-1993. SUBJECTS:
      198 cases of Alzheimer's disease (ADRDA-NINCDS diagnostic criteria) were compared
      to two selected control groups (164 other dementias and 176 non-dementing group)
      with respect to their smoking history. MAIN OUTCOME MEASURE: Relative risk (odds
      ratio) of Alzheimer's disease. RESULTS: The odds ratio for Alzheimer's disease in
      patients who smoked was 0.68 (95% CI 0.47-0.98). The negative association was
      statistically significant only in male patients, OR 0.45 95% CI (0.23-0.87), p <
      0.05. The inverse association was also only significant in patients with family
      history of dementia, OR 0.34 95% CI (0.12-0.92), p < 0.05. CONCLUSION: The study
      supports previous findings of an inverse relationship between smoking and
      Alzheimer's disease. This, however, does not suggest that smoking is used as a
      preventive measure for Alzheimer's disease.

PMID- 9152712
TI  - High proportion of dementia with Lewy bodies in the postmortems of a mental
      hospital in Germany.
AB  - OBJECTIVE: Dementia with Lewy bodies (DLB) is under-recognized in Germany. No
      data on the number of patients suffering from this condition in Germany are
      available at present. We were interested in the proportion of DLB in the
      postmortems of demented inpatients in the care of a psychogeriatric service.
      DESIGN: In a retrospective study we examined consecutive postmortems of
      inpatients who died in one mental hospital. SETTING: A suburban and rural old age
      psychiatry service in Germany. PATIENTS: 103 consecutive postmortems had been
      performed from 9/1987 to 6/1995. Fifty-nine (57.3%) of all cases warranted the
      clinical diagnosis of dementia (DSM-III-R). MEASURES: The causes of dementia were
      examined histologically. Lewy bodies (LBs) were detected with ubiquitin
      immunohistochemistry. RESULTS: DLB was the third most frequent cause of dementia
      (13.6% of demented), after dementia of Alzheimer's type (DAT) (35.6%) and mixed
      DAT and vascular dementia (15.3%), but ahead of 'pure' vascular dementia (MID).
      The DLB group showed a male preponderance compared with the DAT, MID and mixed
      group of our series. The DLB patients died younger than the DAT patients. The
      differences, however, were not statistically significant. All DLB cases showed
      neurofibrillary and amyloid pathology sufficient to warrant an additional
      diagnosis of DAT. Cases with 'pure' LB pathology had not been detected in our
      series. CONCLUSIONS: Our results indicate that by using appropriate methods, ie
      ubiquitin immunohistochemistry, a considerable number of DLB cases can be
      detected in postmortems of demented patients from German mental hospitals.

PMID- 9152713
TI  - Dual diagnosis in elders discharged from a psychiatric hospital.
AB  - Recent evidence indicates persons 60 years and over experience significant
      alcohol and substance abuse problems. Since a combination of alcoholism and
      depression is likely to increase the relative rsk of suicide, it is important to
      examine the prevalence of dual diagnosis in older adults. The purpose of this
      study is to examine the prevalence and correlates of dual diagnosis in older
      psychiatric inpatient populations and compare our results with findings from
      studies of younger hospitalized dually diagnosed patients. A retrospective chart
      audit was performed on 101 elders who were discharged from three psychiatric
      hospitals. Clinical variables that were examined included length of hospital
      stay, psychiatric and medical diagnoses, medications and history of suicidal
      ideation or intent. The leading psychiatric disorder diagnosis for our sample of
      hospitalized psychiatric elders was depression. Over one-third (37.6%) had a
      substance abuse disorder in addition to a psychiatric disorder, and almost three
      fourths (71%) of this 'dual diagnosis' group abused alcohol and 29% abused both
      alcohol and other substances. In addition, significantly more elders in the "dual
      diagnosis' group (17.7%) than in the group with only a mental disorder diagnosis
      (3.3%) made a suicide attempt prior to admission to the hospital. Because,
      affective disorders in conjunction with alcohol abuse are the most frequently
      found disorders in completed suicides, our findings have important relevance for
      the advocating of routine use of diagnostic assessment and screening for both
      substance abuse and mental disorders in this population.

PMID- 9152714
TI  - Variables which distinguish patients fulfilling clinical criteria for dementia
      with Lewy bodies from those with Alzheimer's disease.
AB  - OBJECTIVES: To compare patients fulfilling clinical criteria for Lewy body
      dementia with those meeting clinical criteria for Alzheimer's disease. DESIGN:
      Prospective cohort study. SETTING: Psychiatric services and a memory clinic.
      SAMPLE: 124 patients with DSM-III-R dementia. MEASURES: The assessment included
      the GMS/HAS/SDS package, the CAMCOG, the Cornell Depression scale and the Burns
      Symptom Checklist. Dementia was diagnosed according to DSM-III-R, NINCDS ADRDA,
      McKeith, Byrne, Hachinski and HAS AGECAT criteria. RESULTS: Patients meeting
      McKeith et al. criteria for senile dementia of Lewy body type were significantly
      more likely to have clouding of consciousness, significant Parkinsonian symptoms
      and less severely impaired recent memory than patients with NINCDS ADRDA
      Alzheimer's disease. Each of these variables also distinguished patients meeting
      Byrne et al.'s criteria for dementia with Lewy bodies from those with a diagnosis
      of Alzheimer's disease. CONCLUSIONS: It is suggested that one set of criteria
      could encompass those overlapping groups of patients. Work is needed to further
      develop the diagnostic criteria for Lewy body dementia.

PMID- 9152716
TI  - Education and decline in cognitive performance: compensatory but not protective.
AB  - The association between education and cognitive change was investigated in a
      large community sample of elderly people followed up after 3.6 years. Lower
      education was predictive of decline on the Mini-Mental State Examination (MMSE)
      and on tests of language and knowledge, but not on tests of cognitive speed,
      memory or reaction time. The effects of education were not attenuated when
      adjusted for health, disability or activity level. The findings suggest that
      education slows the rate of decline on crystallized intelligence, but not other
      cognitive abilities. Education may compensate for neurodegenerative changes
      rather than protect against them.

PMID- 9152715
TI  - Selegiline in the treatment of behavioural disturbance in Alzheimer's disease.
AB  - OBJECTIVE: The purpose of this study was to examine the behavioural and cognitive
      effects of selegiline in a group of moderately behaviourally disturbed AD
      patients. DESIGN: This was a 14-week randomized double-blind placebo-controlled
      study of selegiline (10 mg) and placebo. SETTING: An outpatient clinic in an
      urban-based tertiary referral centre in the USA. PATIENTS: Twenty-five
      outpatients meeting NINCDS criteria for probable Alzheimer's disease with
      associated behavioural disturbance. MEASURES: The Brief Psychiatric Rating Scale
      (BPRS), the Dementia Mood Assessment Scale (DMAS) and the Alzheimer Disease
      Assessment Scale (Cognitive) (ADAS-COG). RESULTS: In the primary analysis,
      improvement on the BPRS and DMAS scores with selegeline treatment did not. reach
      statistical significance. A secondary analysis using a parallel design showed a
      significant benefit of drug treatment on BPRS scores with a trend towards
      improvement on the DMAS. Among the 10 subjects who could be tested, there was a
      significant improvement in cognitive function on the ADAS-COG with selegiline
      compared to placebo. CONCLUSIONS: Short-term selegiline treatment produced an
      improvement in behaviour and had a significant effect on cognition in a subset of
      testable patients.

PMID- 9152717
TI  - Behaviour disturbance and other predictors of carer burden in Alzheimer's
      disease.
AB  - OBJECTIVE: To investigate predictors of carer burden in Alzheimer's disease (AD).
      DESIGN: Two cohorts were formed, one comprising AD patients, the other comprising
      their primary carers. The relationship of patient and carer variables to carer
      burden was investigated. SETTING: An urban hospital memory clinic. PARTICIPANTS:
      A convenience sample of 50 patients meeting NINCDS-ADRDA for probable AD, age
      range 60-87, and their primary carers, age range 31-84. MEASURES: The Cambridge
      Cognitive Examination (CAMCOG), the Mini-Mental State Examination (MMSE), the
      Baumgarten et al. Dementia Behaviour Disturbance Scale, the Blessed-Roth Dementia
      Scale, the Personal Self-Maintenance Scale, the Zarit Burden Interview and the
      Vaux et al. Social Support Appraisals (SS-A) and Social Support Behaviours (SS-B)
      Scales. RESULTS: Daughters were particularly prone to burden. Neither patient
      cognitive nor functional status predicted burden. Behaviour disturbance in
      particular, and informal support were significant, but independent, predictors of
      carer burden. CONCLUSIONS: In this study increased carer burden was related
      independently to increased levels of patient behaviour disturbance and decreased
      levels of informal social support. This may have relevance to appropriate
      interventions for carers. As the study was based on a convenience sample of
      memory clinic attenders, replication in less highly selected samples is
      desirable.

PMID- 9152718
TI  - Suicidal thinking in community residents over eighty.
AB  - OBJECTIVE:  MAIN OBJECTIVE: to study the relationship between suicidal thinking
      and both cognitive impairment and depression. DESIGN: Random sample selected for
      interview, all of whom were a cohort in a pre-existing epidemiological study of
      dementia. SETTING: Community residents. PATIENTS AND OTHER PARTICIPANTS:
      Participants aged over 81. Study excluded the following: moved out of area/died/
      too frail/severe communication difficulties/refused interview, refusal by
      GP/family/carers, 300 names selected at random from database. 170 eligible
      participants approached: 31 refused, 125 interviewed, 125 informants approached
      for interview; 118 interviewed. MAIN OUTCOME MEASURES: CAMDEX, 15-item Geriatric
      Depression Scale (GDS), and Scale for Suicidal Ideation (SSI) (including
      informant versions of latter 2 scales). RESULTS: 9 people showed suicidal
      thinking, all women: 6 had clinical evidence of cardiovascular/cerebrovascular
      disease. Those with suicidal thinking showed higher CAMDEX depression scores,
      weaker strength of the wish to go on living, higher rates of expressing wish to
      die and higher rates of depressive illness and mixed DAT/multi-infarct dementia
      as primary psychiatric diagnoses. No significant associations between suicidal
      thinking and GDS scores, Alzheimer-type dementia alone, awareness of memory
      difficulties or severity of dementia. CONCLUSIONS: Results show association
      between suicidal thinking and both depression and mixed DAT/multi-infarct
      dementia, but do not support an association between suicidal thinking and
      awareness of memory problems/severity of dementia. Given the methodological
      limitations, the significance of the results should be viewed with caution.
      Further exploration of the role of cerebrovascular disease in depressive disorder
      is suggested.

PMID- 9152719
TI  - Gender and interactions between care staff and elderly nursing home residents
      with dementia.
AB  - OBJECTIVE: This study explores the relationship between gender and the
      interactions of care staff and elderly people with dementia in residential care.
      DESIGN: Non-participant, time-sampling observation and coding of interactions
      between staff and residents. SETTING: 36-bed independent (not-for-profit) long
      term care unit. SUBJECTS: 36 elderly people with dementia (19 men and 17 women);
      37 care staff (30 women and 7 men). MEASURES: The Quality of Interactions
      Schedule (QUIS). RESULTS: Male residents initiated significantly more
      interactions with staff than female residents. Men did not initiate interactions
      with female staff significantly more often than with male staff. Women did not
      initiate any interactions with male staff. Female staff initiated more
      interactions with residents than did male staff. Both male and female staff
      initiated a higher proportion of interactions with male residents than with
      female residents. CONCLUSIONS: These findings suggest that gender may be a
      significant factor determining the rate of interactions between staff and
      residents in residential care, but further studies are required to confirm their
      generalizability across settings.

PMID- 9152720
TI  - Proton magnetic resonance spectroscopy in dementia of Alzheimer type.
AB  - Reduced N-acetyl aspartate (NAA) and increased myo-inositol (MI) levels have been
      reported in patients with dementia of Alzheimer type (DAT) in comparison with
      controls. We wished to assess the validity of these findings and to evaluate
      possible correlations of metabolite proportions with cognitive dysfunction in
      DAT. Twelve patients with DAT and 10 healthy age-matched controls were included.
      The severity of dementia was assessed using different scales including the Mini
      Mental State Examination. MRS was performed with a conventional 1.5 Tesla scanner
      in a single voxel in the centrum semi-ovale (TE = 30 ms or TE = 136 ms; TR = 1500
      ms). The evaluation of MRS results was limited by low interrater,
      intermeasurement (different echo times) and test-retest reliabilities, by a high
      interindividual variance and by the failure to measure absolute metabolite
      concentrations. These problems in mind, it was remarkable that previously
      reported reductions of NAA levels in patients with DAT could be reproduced in the
      present sample. The proportion of NAA was diminished in demented subjects in
      comparison with controls (37% vs 44.90%, short TE). A non-significant trend
      towards minor reductions of creatine, choline and MI proportions in these
      subjects might indicate that proportions of other metabolites necessarily
      increase when NAA is reduced. Cognitive dysfunction of demented subjects was
      significantly correlated with reductions of NAA, but not with increases of MI.
      Due to the present technical and methodological problems and to the non
      specificity of findings, proton MRS cannot be applied to support the diagnosis of
      DAT in a clinical setting.

PMID- 9152721
TI  - Apolipoprotein E genotypes and serum lipid levels in Alzheimer's disease and
      multi-infarct dementia.
AB  - OBJECTIVE: Assessment of apolipoprotein E genotype, serum cholesterol,
      triglycerides, high density lipoprotein-cholesterol and low density lipoprotein
      cholesterol levels in different types of dementia. SUBJECTS: 102 consecutive
      referrals to an old age psychiatry service based at Manchester were classified
      according to clinical criteria based on ICD 10. RESULTS: Thirty-seven were
      considered to have Alzheimer's disease, 16 multi-infarct dementia and 33 to be
      free from dementia. Sixteen patients, in whom a definitive diagnosis could not be
      reached or sufficient information was not available, were excluded from the
      study. There was an increase in the prevalence of the Apo E4 allele in both
      Alzheimer's disease (chi 2 = 3.82, p < 0.05) and multi-infarct dementia (chi 2 =
      1.93, p < 0. = 0.16) by Wald tests compared to individuals without dementia. The
      increased prevalence of the E4 Allele in multi-infarct dementia was not related
      to serum lipid levels. CONCLUSION: The hypothesis that the onset of multi-infarct
      dementia may be precipitated by E4's mediation of higher serum cholesterol levels
      is not supported by the present study.

PMID- 9152722
TI  - Head injury and the risk of Alzheimer's disease: a case control study.
AB  - OBJECTIVES: The objective of this study is to examine the association between
      Alzheimer's disease and head injury in elderly patients referred to an EMI unit.
      METHOD: An unmatched case control study comparing 198 cases of Alzheimer's
      disease (NINCDS-ADRDA diagnostic criteria) to selected controls (164 other
      dementias and 176 non-dementing group) with respect to history of head trauma,
      with or without loss of consciousness, prior to the onset of dementia. SETTING:
      EMI unit in Warrington serving an elderly population of 28,000. The subjects
      included all patients referred to and seen by the first author during a 2-year
      study period 1991-1993. MAIN OUTCOME MEASURE: Relative risk (odds ratio) of
      Alzheimer's disease. RESULTS: For having history of head injury, the odds ratio
      was 1.52 (0.98-2.35), significant only in male patients (OR 2.1 p < 0.05). For
      dementias other than Alzheimer's disease the odds ratio of head injury was 2.36
      and 2.46 for all dementias combined (p < 0.05). CONCLUSION: The study confirms a
      positive association between reported head injury and Alzheimer's disease as well
      as non-Alzheimer type dementia. Head trauma did not appear to be a specific risk
      for Alzheimer's disease as previously claimed. The association was modified by
      sex being only significant in male patients.

PMID- 9152723
TI  - Magnetic resonance imaging correlates of memory impairment in the healthy
      elderly: association with medial temporal lobe atrophy but not white matter
      lesions.
AB  - OBJECTIVE: To investigate the neuroradiological correlates of age-related
      cognitive decline in the elderly. DESIGN: A sample of healthy control subjects
      underwent magnetic resonance imaging (MRI) scanning and cognitive testing.
      SETTING: Melbourne, Australia. PARTICIPANTS: 40 volunteers over the age of 55 who
      were spouses of subjects seen in a hospital memory clinic, subjects from a
      register of normal volunteer subjects (not staff) kept for research purposes or
      residents of a retirement hostel. MEASURES: Hippocampal and amygdala (HA)
      atrophy, periventricular lesions (PVL) and deep white matter lesions (DWML) were
      rated by two radiologists blind to cognitive test score results. Cognitive
      assessment was by the Cambridge Cognitive Examination (CAMCOG). RESULTS: After
      controlling for age and education, lower scores on the memory subscale of the
      CAMCOG were associated with the presence of HA atrophy, but not with DWML or PVL.
      CONCLUSIONS: HA atrophy on MRI is associated with impaired memory performance in
      the healthy elderly, while PVL and DWML are not. Further study should determine
      whether HA atrophy is a risk factor for developing dementia.

PMID- 9152724
TI  - Can frontotemporal dementia and Alzheimer's disease be differentiated using a
      brief battery of tests?
AB  - OBJECTIVE: To compare the performance of patients with frontotemporal dementia
      (FTD) and Alzheimer's disease (AD) on a range of simple neuropsychological tests.
      DESIGN: A battery of neuropsychological tests easily applied at the bedside,
      consisting of traditional tests of memory, attention and executive function, were
      given together with tests of motor sequencing and examination of frontal release
      signs. In addition, we devised a theoretically motivated test of dual attention-a
      story with distraction which also contained a 'social dilemma'. SETTING:
      Specialist memory and cognitive disorders clinic. PATIENTS: 12 patients with FTD
      and 12 patients with AD, matched for overall level of dementia on the Mini-Mental
      State Examination, were selected. RESULTS: In general, the difference in results
      between FTD and AD patients was small. However, a composite score derived from
      the presence of a grasp and pout reflex, the number of perseverations during
      category fluency for animals and response to the social dilemma within the two
      stories produced a sensitivity of 83.3% and specificity of 91.6%. There was also
      a highly significant difference between patients with FTD and AD in scores
      achieved on the Clinical Dementia Rating Scale reflecting the marked change in
      behaviour that patients with FTD suffer, even at a stage when memory functions
      are well preserved. CONCLUSION: Traditional neuropsychological tests were poor at
      differentiating cases of FTD and AD; however, a composite (SIFTD) score appears
      potentially useful but requires prospective validation. Better methods of
      assessing the changes in comportment that characterize the early stages of FTD
      are required.

PMID- 9152725
TI  - A study of aggression among referrals to a community-based psychiatry of old age
      service.
AB  - OBJECTIVE: The aims of the study were to examine the prevalence of aggressive
      behaviour in a non-selected community-based population, to identify clinical and
      sociodemographic variables associated with aggression and to examine the
      relationship between aggression and outcome at 2-year follow-up. DESIGN: Case
      series, using the Ryden Aggression Scale as a retrospective measure of
      aggression. SETTING: A community-based specialist psychiatry of old age service.
      PARTICIPANTS: All referrals to the service over a 3-month period. RESULTS: Of the
      42 subjects included in the study, 25-patients had a diagnosis of dementia.
      Aggressive behaviour was reported in 18 patients, this being verbal only in nine
      cases and both verbal and physical in nine cases. Sexual aggression and self
      injurious behaviour were each reported in one case only. Aggression was found to
      be positively associated with a diagnosis of dementia and high physical
      dependency but was not found to be associated with age, sex, physical illness or
      the use of psychotropic medication. At 2-year follow-up, aggressive patients were
      found to have a higher rate of admission to psychiatric inpatient or residential
      care and tended to have a higher use of neuroleptic drugs. CONCLUSIONS: These
      findings suggest that aggression is a significant problem for community-based
      elderly people and their carers, may increase the likelihood of admission into
      long-term care and that a reliable instrument to measure aggression would be
      useful in the clinical assessment of this population.

PMID- 9152726
TI  - Depression in older medical inpatients: one-year course and outcome.
AB  - OBJECTIVE: This 1-year follow-up survey of 214 medical inpatients aged 65 and
      older describes the outcome of major depressive episode (MDE), determines the
      incidence of new episodes and identifies factors associated with outcome and with
      new episodes of MDE. METHOD: Follow-up information was obtained from 160
      patients, 69 men and 91 women. RESULTS: Of the 48 cases of MDE who were
      interviewed, 44% improved. Underlying dysthymic disorder strongly influenced
      outcome: of 21 cases of MDE alone, 62% were improved at follow-up; of the 27
      cases in which MDE was superimposed on dysthymic disorder initially, only 30%
      were improved. New episodes of MDE occurred in 21% of patients, and were
      associated with dysthymic disorder initially and with change of meaning of life.
      CONCLUSIONS: Among older medical inpatients, MDE, particularly when superimposed
      upon dysthymic disorder, is a persistent condition. Randomized trials are
      necessary to identify efficacious treatments.

PMID- 9152727
TI  - Orthostatic hypotension and low blood pressure in organic dementia: a study of
      prevalence and related clinical characteristics.
AB  - OBJECTIVE: To determine the prevalence of orthostatic hypotension (OH), low blood
      pressure and dizziness, falls and fractures in patients with organic dementia.
      DESIGN: We prospectively studied 151 patients, assessing the prevalence of OH,
      hypertension, heart disorders, diabetes mellitus and the use of medication
      possibly associated with OH. SETTING: The patients were admitted to our
      psychogeriatric clinic as part of routine clinical investigation of their
      dementia. PATIENTS: Forty-six patients with Alzheimer's disease (AD), 28 patients
      with frontotemporal dementia (FTD) and 77 patients with vascular dementia (VaD)
      were investigated. MAIN OUTCOME MEASURE: Due to the paucity of information about
      the prevalence of OH in organic dementia, this study is mainly explorative in
      nature, thus preventing explicit hypothesis formulation. However, clinical
      impressions indicated a higher prevalence of OH in organic dementia than normally
      seen in healthy elderly. RESULTS: OH/low blood pressure was present in 39-52% of
      the patients. The majority reached their maximum systolic decrease within 5
      minutes of standing, but in 20-30% the maximum blood pressure drop occurred after
      5 minutes or later. In 38%, the systolic blood pressure drop was more than 40 mm
      Hg. Hypertension and heart disease was found only in AD and VaD, with no
      difference between those with and without OH/low blood pressure. Falls and
      fractures were common in orthostatic and hypotensive patients, with an incidence
      of more than 50% in AD and VaD. CONCLUSIONS: The results support our clinical
      impressions that OH and low blood pressure is common and an important factor in
      organic dementia.

PMID- 9152728
TI  - The experience of dying with dementia: a retrospective study.
AB  - OBJECTIVE: To describe the last year of life of people with dementia, their
      symptoms, care needs, use of and satisfaction with health services and the
      bereavement state of the respondent. METHODS: The study is drawn from the
      Regional Study of Care for the Dying, a retrospective sample survey of the
      carers, family members or others who knew about the last year of life of a random
      sample of people age 15 and over dying in the last quarter of 1990. The samples
      were drawn in 20 English health districts which, although self-selected, were
      nationally representative. There was a total of 3696 patients (response rate of
      69%) dying from all causes. Within this sample, 170 dementia patients were
      identified and compared with 1513 cancer patients. RESULTS: The symptoms most
      commonly reported in the last year were mental confusion (83%), urinary
      incontinence (72%), pain (64%), low mood (61%), constipation (59%) and loss of
      appetite (57%). Dementia patients saw their GP less often than cancer patients
      and their respondents rated GP assistance less highly. Dementia patients needed
      more help at home compared with cancer patients, and received more social
      services; 78% of respondents for dementia patients and 64% for cancer said they
      had come to terms with the patient's death. CONCLUSION: Patients dying from
      dementia have symptoms and health care needs comparable with cancer patients.
      Greater attention should be given to these needs.

PMID- 9152729
TI  - Insight into auditory hallucinations and psychosis.

PMID- 9152730
TI  - Risperidone in the treatment of psychosis and concomitant buccolinguomasticatory
      dyskinesia in the elderly.

PMID- 9152731
TI  - Charles Bonnet syndrome, time to drop the name?

PMID- 9152732
TI  - Current awareness in geriatric psychiatry.

PMID- 9152733
TI  - Lactate-bicarbonate interrelationship during exercise and recovery in lean and
      obese Zucker rats.
AB  - OBJECTIVE: To determine the relationship between muscle-derived lactate at
      fatigue and earlier onset of fatigue in the obese rat subjected to intense
      exercise. DESIGN: Rats were subjected to a short, intense exercise protocol on a
      treadmill. Blood was drawn from hind leg vein and artery during exercise and up
      to 1 h afterwards. Assuming an exercise respiratory quotient of 1.0, the extra
      carbon dioxide released was computed and assumed to be displaced by equimolar
      amounts of lactic acid produced by the rat during exercise. SUBJECTS: Conscious
      female adult Zucker lean and Zucker obese rats. MEASUREMENTS: Oxygen consumption
      and carbon dioxide release. Lactate and bicarbonate levels in hind leg venous and
      arterial blood; balances were estimated by measuring blood flow with fluorescent
      microspheres. Lactate levels in periovaric white adipose tissue were also
      measured. RESULTS: Muscle released, during exercise and post exercise roughly 2.3
      mmol lactate in lean rats and 2.6 mmol in obese ones. Of these amounts, hind leg
      lactate release accounted for 0.40 mmol in lean rats and only 0.11 in the obese
      ones, which showed a release of acid (mainly lactate) elsewhere in the rats
      totalling about 19.9 mmol CO2 in lean rats and 4.4% in the obese ones; that is
      both hind quarters accounted for only 17.2% of all lactate produced in the lean
      rats and 4.4% in the obese ones. The amount of lactate produced by the rats was
      roughly similar. White adipose tissue lactate levels (in the basal state and
      after exercise) were much higher than could be expected from blood sources alone,
      indicating an active production of lactate. CONCLUSION: Fatigue appears earlier
      in the obese rats than in lean ones because of loss of buffering ability caused
      by massive extra-muscular glycolysis (probably in adipose tissue) and lactate
      production triggered by exercise-induced adrenergic stimulation.

PMID- 9152734
TI  - Associations of adiposity with prevalent coronary heart disease among elderly
      men: the Honolulu Heart Program.
AB  - OBJECTIVE: To assess associations of adiposity with prevalent coronary heart
      disease (CHD) among elderly men. DESIGN: A cross-sectional epidemiologic study
      conducted between 1991 and 1993. SUBJECTS: 3741 Japanese-American men from the
      Honolulu Heart Program who were 71-93 y of age. MEASUREMENTS: CHD included
      documented myocardial infarction (electrocardiographic and enzyme criteria),
      acute coronary insufficiency, angina pectoris leading to surgical treatment
      identified through hospital surveillance, and reported history of heart attach or
      angina pectoris requiring hospitalization or surgical treatment. BMI was
      calculated as weight in kg divided by height in square meters. Waist
      circumference was measured at the horizontal level of the umbilicus and WHR was a
      ratio of waist circumference to hip circumference measured at the horizontal
      level of the maximal protrusion of the gluteal muscles. RESULTS: An elevated
      prevalence of CHD was observed in the elderly men with high BMI, WHR and waist
      circumference. The significant associations of BMI and waist circumference with
      CHD persisted after adjustment for fasting glucose, physical activity and pack
      years of cigarette smoking but were no longer significant (odds ration (OR) =
      1.03, 95% confidence level (CI) 0.94-1.12 and OR = 1.09, CI = 0.99-1.20,
      respectively) after adjustment for high density lipoprotein cholesterol (HDL-C).
      Also, the association of BMI with CHD was not found to be independent of
      abdominal adiposity. However, the associations of WHR and waist circumference
      remained significant (OR = 1.20, CI = 1.08-1.33 and OR = 1.17, CI = 1.01-1.37,
      respectively) after additional adjustment for BMI. In addition, the association
      of WHR with CHD was consistently significant and independent of fasting glucose,
      physical activity, smoking and HDL-C (OR = 1.11, CI = 1.00-1.23). CONCLUSION: WHR
      is associated with CHD independent of HDL-C and BMI, whereas the relation of BMI
      and waist circumference with CHD may be mediated through a relation of BMI and
      waist circumference with HDL-C level.

PMID- 9152735
TI  - Factors associated with joint pain among postmenopausal women.
AB  - OBJECTIVES: To investigate potential factors associated with joint pain among
      postmenopausal women. DESIGN: Population-based cross-sectional study. SUBJECTS:
      Six hundred and ninety postmenopausal Japanese-American women from the Hawaii
      Osteoporosis Study (age: 55-93 y). MEASUREMENTS: Data for this study were
      collected at the 1992-1994 examination of the Hawaii Osteoporosis Study, except
      that data on spinal osteoarthritis were obtained based on radiographs at
      examinations before 1987. Information on painful joints at a variety of skeletal
      sites, smoking, and physical activity was collected by questionnaire. Bone
      density was measured at the lumbar spine, distal and proximal radius, and heel.
      Quantitative bone ultrasound was also measured at the heel. Prevalent vertebral
      fractures were identified on lateral spine radiographs using 3 s.d. below the
      normal population mean as the cutoff. Non-spine fractures were identified based
      on self-report, and were verified using medical records. RESULTS AND CONCLUSIONS:
      In this cross-sectional analysis, bone density, quantitative bone ultrasound,
      prevalent vertebral fractures, and non-spine fracture were not significantly
      associated with joint pain. Greater body weight or body mass index were
      significantly and positively associated with joint pain at most weight-bearing
      joints. The results suggest that a substantial proportion of joint pain at these
      sites could be prevented by avoidance of excess weight, provided the association
      is causative. Longitudinal studies are needed to confirm the observed cross
      sectional associations.

PMID- 9152736
TI  - Effect of obesity on total and free insulin-like growth factor (IGF)-1, and their
      relationship to IGF-binding protein (BP)-1, IGFBP-2, IGFBP-3, insulin, and growth
      hormone.
AB  - OBJECTIVES: We investigated the effect of obesity on the serum levels of total
      and free IGF-1 and their relationship to the circulating levels of insulin and
      IGF binding proteins (IGFBPs) in age and sex-matched groups. SUBJECTS: The study
      included 43 obese subjects (ideal body weight; IBW > 120%) and 45 controls (IBW <
      100%). All of the subjects were male. MEASUREMENT: Total IGF-1, free IGF-1, IGFBP
      1, IGFBP-2, IGFBP-3, and insulin were measured in obese subjects and normal
      control subjects. RESULTS: No significant differences in the circulating levels
      of total and IGFBP-3 were observed between the obese and control groups. In
      contrast to total IGF-1, free IGF-1 in obese subjects was significantly increased
      compared to normal controls (P < 0.05). Serum total and free IGF-1 were inversely
      correlated with age (r = -0.42, P = 0.001, and -0.44, P = 0.001). Fasting serum
      insulin concentrations were elevated in all the obese subjects (P < 0.05) and
      positively correlated with IBW (r = 0.57, P = 0.001). The levels of serum GH and
      IGFBP-1 were suppressed in all the obese subjects (P < 0.05). IGFBP-1 was
      inversely correlated with IBW (r = -0.51, P = 0.001) and serum insulin
      concentrations (r = -0.48, P = 0.001). The IGFBP-2 concentrations were also
      suppressed in obese subjects and inversely related to free IGF-1 (r = -0.48, P =
      0.001). Using multiple linear regression analysis, total IGF-1 and insulin
      concentrations were positively correlated (r = 0.58, P = 0.001) and free IGF-1
      and IGFBP-1 concentrations were negatively correlated (r = -0.57, P = 0.001).
      CONCLUSION: We confirmed that total IGF-1 and IGFBP-3 concentrations were not
      significantly different between the obese and control groups, despite GH
      hyposecretion in obesity. We also found that free IGF-1 concentrations were
      higher in obese subjects than in normal controls. It seems likely that
      overnutrition and chronic hyperinsulinaemia in obesity may alter this regulated
      growth response by insulin stimulation of IGF-1 production and suppression of
      hepatic IGFBP-1 and IGFBP-2 production, which may inhibit IGF-1 bioactivity.

PMID- 9152737
TI  - Influence of obesity on plasma lipoproteins, glycaemia and insulinaemia in
      patients with familial combined hyperlipidaemia.
AB  - The influence of obesity on blood pressure and plasma lipoproteins, glucose and
      insulin levels was investigated in patients with familial combined
      hyperlipidaemia (FCH). Sixty seven FCH patients mean age 49.0 +/- 8.9 y (45 male,
      22 female) defined as obese (BMI > or = 27 kg/m2, n = 39) or non-obese (BMI < 27
      kg/m2, n = 28) were compared with control subjects matched for age, gender and
      body weight. Blood pressure, plasma lipoproteins, glucose and insulin were
      measured at baseline and following standard oral glucose load. The analysis
      indicate that FCH subjects with BMI > or = 27 kg/m2 had significantly higher
      systolic and diastolic blood pressure, blood glucose and insulin levels following
      oral glucose tolerance test than those with BMI < 27 kg/m2. Fasting plasma
      insulin values were also significantly higher in the BMI > or = 27kg/m2 subjects
      (138.5 +/- 66.6 vs 111.0 +/- 29.9 pmol/l, respectively, P < 0.05). Quantification
      of the area under the curve of the insulin secretion showed hyperinsulinaemia in
      64.1% of patients with BMI > or = 27kg/m2 compared to 28.5% in the group with BMI
      < 27 kg/m2 (P < 0.01). Plasma insulin values were positively related to
      triglyceridaemia. There were no differences in the plasma lipid values between
      the two FCH groups. We conclude that fasting and post-glucose stimulated plasma
      insulin levels are frequent findings in patients with FCH when compared with
      control subjects of similar age, gender and BMI. Moreover, obesity (BMI > or =
      27kg/m2) exacerbates the hyperglycaemia, hyperinsulinaemia and blood pressure
      values in these FCH subjects. These factors, together with lipid abnormalities,
      can predispose to the elevated risk of cardiovascular disease observed in FCH
      subjects.

PMID- 9152738
TI  - Relationship of metabolic variables to abdominal adiposity measured by different
      anthropometric measurements and dual-energy X-ray absorptiometry in obese middle
      aged women.
AB  - OBJECTIVES: To investigate how abdominal adiposity assessed by different
      anthropometric measurements and dual-energy X-ray absorptiometry measurements is
      associated with metabolic risk factors for cardiovascular disease and non-insulin
      dependent diabetes mellitus in obese women. DESIGN: Cross-sectional study.
      SUBJECTS: Forty-three healthy, obese, middle-aged women (age: 29-64 y, BMI: 28-42
      kg/m2). MEASUREMENTS: (1) Anthropometry: waist circumference, waist-to-hip ratio,
      waist-to-height ratio, abdominal sagittal and transverse diameters and their
      ratio. (2) Dual-energy X-ray absorptiometry: the amount of total and regional
      abdominal fat. (3) Metabolic measurements: serum total, VLDL, LDL, HDL
      cholesterol, triglycerides, fasting and postglucose serum insulin and glucose.
      RESULTS: After adjustment for age and BMI, all the anthropometric measurements
      except waist-to-hip ratio and waist-to-height ratio related significantly to HDL
      and LDL cholesterol. On the other hand, waist-to-hip ratio and waist-to-height
      ratio showed an association with triglycerides. In addition, all the
      anthropometric measurements except transverse diameter correlated significantly
      with fasting insulin and fasting glucose. Waist-to-hip ratio was the only measure
      that associated with 2 h glucose concentration. The differences between the
      correlation coefficients were not statistically significant in the z-transformed
      correlation coefficient test. As to dual-energy X-ray absorptiometry results, the
      region from the dome of diaphragm to the top of femur ('abdominal fat') and the
      area between the first and the fourth lumbal vertebrae ('upper lumbal fat')
      inversely related to HDL cholesterol and positively to triglycerides. Both of
      these regions correlated significantly with fasting insulin, and "upper lumbal
      fat' associated also with fasting glucose even after adjustment for age and BMI.
      CONCLUSION: None of the anthropometric measurements (waist circumference, waist
      to-hip ratio, waist-to-height ratio or sagittal diameter) was significantly
      superior to others to assess the metabolic risk profile. 'Upper lumbal fat' (the
      area between the first and the fourth lumbal vertebrae) measured by dual-energy X
      ray absorptiometry discerned obese women with elevated fasting insulin and
      fasting glucose.

PMID- 9152739
TI  - Physical activity and body composition in 10 year old French children: linkages
      with nutritional intake?
AB  - OBJECTIVES: To investigate the relationships between physical activity, dietary
      intake and body composition in children. DESIGN: A cross-sectional study on
      physical activity, nutritional intakes and body composition conducted in 86
      healthy 10 y old French children. In addition, growth parameters and nutritional
      intakes were available from the age of 10 months. MEASUREMENTS: Physical activity
      level (using a validated activity questionnaire over the past year), nutritional
      intake (dietary history method), anthropometric measurements (body weight,
      height, arm circumference, triceps and subscapular skinfolds, Body Mass Index
      (BMI), arm muscle and arm fat areas calculated from these measurements) at the
      age of 10 y. Anthropometric measurements and nutritional intakes were recorded in
      the same children at the age of 10 months and every 2 y from the age of 2 y.
      RESULTS: At the age of 10 y, active children ingested significantly more energy
      than less active children, mostly due to higher energy intake at breakfast and in
      the afternoon. This higher energy intake was accounted for by increased
      consumption of carbohydrates (281 g vs 246 g; 49.6% vs 47.4% of total energy).
      Even if the amounts of fat consumed were similar in both groups (90 g vs 84 g; P
      = 0.09), the percentage of fat intake was lower in active children (35.4% vs
      37.4%; P = 0.04). The percentage of protein was not different (14.9% vs 15.3%; P
      = 0.33). In spite of a higher energy intake in the active group, active and less
      active children had similar BMI at the age of 10 y. However, their body
      composition differed significantly: active children had a higher proportion of
      fat-free mass, a lower proportion of fat-mass as measured in the arm and they had
      a later adiposity rebound. Fatness was significantly and positively associated
      with the time spent watching television and video games. CONCLUSIONS: Physical
      activity was associated with improved body composition and growth pattern. This
      association may be related to nutritional changes: active children consumed more
      energy by increasing carbohydrate, thus reducing the relative fat content of
      their diet. These results provide support to encourage physical activity during
      childhood.

PMID- 9152740
TI  - Is walking for exercise too exhausting for obese women?
AB  - OBJECTIVES: As exhaustion and pain during walking seem to be common problems
      among obese women, we decided to analyse the relative oxygen cost (% VO2max) in
      obese women during level walking. SUBJECTS: Fifty-seven obese female outpatients,
      44.1 +/- 10.7 y, BMI 37.1 +/- 3.4 kg.m-2. METHODS: Walking tests at a self
      selected, comfortable speed were performed indoors. Speed was measured with a
      speedometer, oxygen consumption (VO2) with the argon-dilution method and oxygen
      cost was estimated. Heart rate was measured; perceived exertion and pain were
      assessed with Borg's Category Ratio scale, CR10. Maximum oxygen uptake
      (VO2max/kg) was predicted from a submaximum bicycle ergometry test. RESULTS: The
      women walked more slowly, 70.9 +/- 5.6 m.min-1 (P < 0.0001), and had higher VO2,
      1.2 +/- 0.2 l.min-1 (P < 0.001), than normals. A majority experienced exertion
      and some experienced pain. Their VO2max/kg, 21.2 +/- 5.0 ml.kg-1.min-1, was less
      than for normals (P < 0.0001). The mean % VO2max during walking was 56%, which
      was higher than in normal subjects 36% (P < 0.0001). Significant correlations
      between % VO2max and VO2max/kg (P < 0.0001), heart rate during walking (P =
      0.0009) and age (P = 0.0081), respectively, were found. CONCLUSION: Very low
      VO2max/kg in obese women, rather than severe obesity per se, seems the most
      important factor to cause high % VO2max during walking. This might explain why
      many obese women perceive the exertion to be excessive and cannot follow the
      advice of their clinicians to exercise through long and brisk walks.

PMID- 9152741
TI  - Gastrointestinal hormones and gastric emptying 20 years after jejunoileal bypass
      for massive obesity.
AB  - OBJECTIVE: Some studies have shown a more rapid gastric emptying in obese
      subjects. Six to twelve months after jejunoileal bypass (JIB) neurotensin (NT)
      and enteroglucagon have been shown to be elevated after food intake. These
      hormones, together with peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) have
      been implicated in the reduction of upper gastrointestinal motility seen after
      infusion of nutrients into the ileum. AIM: To study if the postprandial gut
      hormone pattern and gastric emptying is altered 20 y after JIB. SUBJECTS: Seven
      subjects operated with JIB a mean (s.d.) 20 +/- 3 y ago, with a BMI of 44 +/- 4
      kg/m2 at the time of surgery and 31 +/- 4 at present. For comparison seven sex
      matched non-operated obese controls (BMI 43 +/- 3) were studied. METHODS: Serial
      blood samples were obtained every 10 min after intake of a 280 kcal meal.
      Radioimmunoassays for motilin, cholecystokinin (CCK), NT, PYY and GLP-1 were
      performed. Gastric emptying of a solid meal was studied using a radioactively
      labelled omelette (of 310 kcal) for 120 min). RESULTS: After JIB postprandial
      motilin, CCK, NT, PYY and GLP-1 were elevated compared to non-operated obese
      subjects. Similarly, basal levels of CCK, motilin, GLP-1 and PYY were elevated in
      the operated group. No difference was observed in the rate of gastric emptying
      between the two groups. CONCLUSION: Both fasting and postprandial gut hormone
      levels are elevated 20 y after JIB. The impact of long-term rapid stimulation of
      the ileum and subsequent raised gut hormone levels on gastric emptying is not
      clear.

PMID- 9152742
TI  - Leptin concentrations and insulin sensitivity in normoglycemic men.
AB  - OBJECTIVE: Leptin is a hormone regulating weight in the mouse. Leptin regulates
      food intake and appetite. Leptin concentrations are increased in obese
      individuals suggesting resistance to its effect. However, there is considerable
      variability in leptin levels at each level of adiposity suggesting that
      environmental and genetic factors may regulate leptin concentrations. We examined
      whether subjects with decreased insulin sensitivity have increased leptin levels.
      METHODS: We used a radioimmunoassay to measure serum leptin levels and the
      hyperinsulinemic euglycemic clamp (with indirect calorimetry) to measure insulin
      sensitivity in 87 normoglycemic relatively lean men. RESULTS: Leptin levels were
      significantly correlated with fasting insulin (r = 0.58), insulin area (r =
      0.45), overall (r = -0.57), non-oxidative (r = -0.51) and oxidative (r = -0.51)
      whole body glucose disposal (all P-values < 0.001). After adjustment for body
      mass index, leptin levels remained significantly correlated with fasting insulin
      (r = 0.44), insulin area (r = 0.40), overall (r = -0.40), non-oxidative (r = 
      0.28) and oxidative (r = -0.33) whole body glucose disposal although the
      magnitude of the associations was considerably decreased. Leptin levels were
      significantly related to insulin sensitivity in both less obese and more obese
      subjects. CONCLUSIONS: We conclude that leptin concentrations are related to
      insulin resistance and insulin concentrations in relatively lean normoglycemic
      men and these associations are to some extent independent of body mass index.
      Thus, subjects with insulin resistance may be relatively resistant to the effects
      of leptin.

PMID- 9152743
TI  - Investigation of the relationship between infant temperament and later body
      composition.
AB  - OBJECTIVE: To investigate the ability of maternally-rated infant temperament to
      predict fatness and activity patterns in early childhood. DESIGN: Longitudinal
      investigation of infants studied at 12 weeks and followed up at 2-3.5 y of age.
      SUBJECTS: Thirty healthy full-term infants from the general population.
      MEASUREMENTS: Body composition, behavioural activity and temperament at 12 weeks;
      anthropometry, body composition, diet and behavioural activity at follow-up.
      RESULTS: Infant temperament predicted later behaviour and fatness. Easily
      soothable infants had leaner childhood skinfold thicknesses (P < 0.02) and were
      more active in childhood (P < 0.025). Infant distress was also related to
      childhood diet composition. CONCLUSIONS: Infant temperament can predict later
      body composition and behaviour. Both energy intake and energy expenditure may be
      mechanisms by which the relationship develops.

PMID- 9152744
TI  - Evening eating and subsequent long-term weight change in a national cohort.
AB  - OBJECTIVE: To examine the association of proportion of daily energy consumed in
      the evening with weight change over 10 y of follow-up. DESIGN: The data used were
      from the First National Health and Nutrition Examination Survey (NHANES I, 1971
      75) Epidemiologic Follow-up Study (NHEFS, 1982-84). The analytic cohort included
      2580 men and 4567 women aged 25-74 y at baseline (NHANES I, 1971-75). The
      proportion of energy consumed in the evening (after 5 pm) was estimated from a 24
      h dietary recall obtained a baseline. Weight change was defined as the difference
      between the follow-up and baseline weights. RESULTS: Mean +/- s.e. of percent
      energy from evening food intake was 46 +/- 0.29 in the analytic cohort. After
      adjustment for multiple covariates, percent energy from evening food intake and
      weight change were unrelated in both men and women. CONCLUSION: Extent of evening
      eating was not a significant predictor of 10 y weight change in the NHEFS cohort.

PMID- 9152745
TI  - Acute effect of exercise and low-fat diet on energy balance in heavy men.
AB  - OBJECTIVE: To quantify the acute effect of the exercise-low-fat diet combination
      on energy balance compared with sedentarity and a high fat diet in overweight
      individuals. DESIGN AND MEASUREMENTS: We assessed the acute effect of exercise
      and ad libitum intake of low-fat foods on daily energy balance. Six heavy men
      participated in two randomly assigned sessions which required a 24 h stay in a
      whole body indirect calorimeter. Sessions were preceded by either a 60 min
      aerobic exercise at 50% VO2 max or a 60 min rest. Subjects were fed a low-fat
      diet (mean FO = 0.89) after exercise and a mixed diet (mean FQ = 0.85) after the
      resting period. RESULTS: The difference in energy balance between the two
      conditions was 7.3 MJ. About half of the effect was attributable to the energy
      surplus expended during exercise whereas the remaining fraction was explained by
      the difference in post-exercise energy balance. CONCLUSION: In heavy men, the
      combination of a low-fat diet and exercise has a strong acute effect on energy
      balance compared to a rest-mixed diet condition.

PMID- 9152747
TI  - Transtympanic myringoplasty in children.
AB  - Our experience with myringoplasty by the transtympanic "push through' technique
      in paediatric patients is described. We have used this method in 40 children
      utilizing autologous temporalis fascia as the graft material. The procedures were
      all performed as day cases under general anaesthesia. The overall success rate
      for perforation closure was 77.5% at 6 months which is comparable to conventional
      methods. We conclude that the "push-through' technique is a safe, simple,
      reliable and cost-effective procedure that can be performed as a day case in
      paediatric patients. It avoids the necessity for pressure bandaging or formal ear
      packing. To our knowledge this is the first paper evaluating this technique in
      children.

PMID- 9152746
TI  - Laryngologic management of infants with the Chiari II syndrome.
AB  - As a part of a prospective multi-disciplinary study, all children born with a
      Chiari II malformation within the Uppsala region during a 3-year period were
      evaluated for any difficulties in breathing or swallowing. The evaluation was
      repeated at regular intervals during their first 18 months. Direct laryngoscopies
      were performed using flexible fiberscopes. Four out of 22 children were found to
      have disturbed breathing. Among those, two suffered from central apnoeic spells
      as well as bilateral vocal fold motion impairment, one from apnoeic spells only
      and one from bilateral vocal fold motion impairment only. All four also had
      dysphagia with aspiration. Three of the children developed respiratory symptoms
      within the first 3 months and the symptoms of the fourth begun within the first 6
      months. One infant with severe symptoms expired at the age of 3 months. The vocal
      fold paralysis, apnoeic spells and swallowing difficulties of another infant
      resolved following active neurosurgical management. The conclusion that
      laryngologic issues are prominent in the severe Chiari II syndrome was further
      supported by a review of four more cases managed in recent years. Laryngologic
      assessment in the neonatal period can help to raise the issue of early
      neurosurgical intervention as well as identify some of the infants who will need
      extensive habilitation. Screening of laryngeal function by means of flexible
      fiberoptic laryngoscopy is recommended.

PMID- 9152748
TI  - Vestibular areflexia as a cause of delayed motor skill development in children
      with the CHARGE association.
AB  - Six cases of the CHARGE association are described that were encountered
      consecutively at an institute for the deaf. Five of them showed external ear
      anomalies and according to expectations all of them showed some degree of hearing
      impairment: two had moderate mixed hearing loss; three had severe to profound
      sensorineural hearing loss; and one was completely deaf. In addition, they all
      had vestibular areflexia and the five cases examined with computer tomography of
      the petrosal bones showed aplasia of the semicircular canals. One case with poor
      visual acuity also showed subnormal optokinetic responses and horizontal pendular
      nystagmus during visual fixation. All these children were initially diagnosed as
      having severe psychomotor retardation, because of their failure to acquire speech
      and their delayed motor skill development. Given the fact that (mild) mental
      retardation was found in only one case, the delayed development could at least in
      part have been caused by vestibular areflexia. The vestibular findings support
      previously reported temporal bone findings that indicate dysplasia or aplasia of
      the superior part of the labyrinth. Early detection of the full extent of
      (multiple) sensory deficits is necessary in children with the CHARGE association
      who have similar abnormalities, because aggressive intervention and special
      educational support are likely to be of great benefit to sensorimotor
      development.

PMID- 9152750
TI  - Profound hearing loss and presence of click-evoked otoacoustic emissions in the
      neonate: a report of two cases.
AB  - Evoked otoacoustic emissions using click stimulus (cEOEs) were recorded in 450
      consecutive children over a 12-month period. Of this group, 102 were babies
      treated in neonatal intensive care unit (NICU), classified as High Risk neonates
      according to the criteria of the Joint Committee on Infant Hearing. Audiologic
      examination in the latter was completed by auditory brainstem responses (ABR).
      Two of the neonates showed a profound hearing loss accompanied by strong cEOEs.
      The two cases are described and discussed together with the possibilities and
      limitations of transient evoked otoacoustic emissions in the auditory screening
      of the neonatal population. Despite the reported rare possibility of pure
      retrocochlear disorders, when cEOEs are used for neonatal screening purposes
      there is an actual risk of missing a profound hearing loss. Nevertheless, the use
      of cEOEs in combination with ABR may contribute to the differential diagnosis
      between cochlear and retrocochlear lesions.

PMID- 9152749
TI  - Neurophysiological evaluation of acute facial paralysis in children.
AB  - Objective evaluation of facial nerve paralysis represents a unique challenge to
      the clinician. Electroneurography (ENoG) and the acoustic reflex (AR) have been
      widely used as neurophysiological tests in an assessment of facial nerve
      function. However, ENoG or AR alone does not suffice diagnostic and prognostic
      purposes of facial function evaluation in children. To further investigate the
      diagnostic aspects of facial nerve paralysis, the prognostic value of AR and
      ENoG, and the time course of the disease in pediatric population, a series of 30
      children with acute facial paralysis were investigated by correlation of findings
      from video-taped House-Brackmann facial grading system. AR and ENoG. The results
      showed that AR was absent or abnormal for thresholds in 68.2% of patients with
      Bell's palsy and normal middle ear function. Shorter duration and higher
      percentage of recovery were found in the children with a normal AR than those
      with an abnormal AR. Three children showed an abnormal tympanogram and hearing
      loss associated with acute facial paralysis. These findings should alert the
      clinician to the presence of a specific, treatable disease in the evaluation of
      Bell's palsy. The percentage of electroneurographic response varied with
      different days after onset. ENoG showed minimal responses at weeks 1 3 after
      onset of Bell's palsy in most patients. The study of the time-course in the
      children with Bell's palsy demonstrated a functional gap in the early (< 1 week)
      and late clinical stage (after 6 weeks) of the disease, suggesting that ENoG
      predicted well only during weeks 1-4 after onset. In general, ENoG showed a good
      recovery in children, however, recurrent Bell's palsy becomes a concern. The need
      for neurophysiological follow-up for possible incomplete recovery of the facial
      nerve is emphasized. It is recommended that AR and ENoG should be included in the
      diagnostic workup when evaluating pediatric facial function.

PMID- 9152751
TI  - Dialogue with other sciences: opportunities for mutual gain.

PMID- 9152752
TI  - Projective identification: the analyst's involvement.
AB  - The author emphasises that what is projected into the analyst is a phantasy of an
      object relationship that evokes not only thoughts and feelings, but also
      propensities towards action. From the patient's point of view, the projections
      represent an attempt to reduce the discrepancy between the phantasy of some
      archaic object relationship and what the patient experiences in the analytical
      situation. For the analyst, too, there are impulses to function in ways that lead
      to a greater correspondence with some needed or desired phantasies. The
      interaction between the patient's and the analyst's needs may lead to the
      repetitive enactment of the painful and disturbing kind that is described. It may
      be very difficult for the analyst to extricate himself (or his patient) from this
      unproductive situation and recover his capacity for reflective thought, at least
      for a while. The difficulty is compounded when the projection into the analyst
      leads to subtle or overt enactments that do not initially disturb the analyst
      but, on the contrary, constitute a comfortable collusive arrangement, in which
      the analyst feels his role is congruent with some internal phantasy. It may be
      difficult to recognise the defensive function this interaction serves for both
      the patient and the analyst and the more disturbing phantasies it defends
      against.

PMID- 9152753
TI  - Interaction and transference.
AB  - The author begins by pointing out that, whereas in classical psychoanalysis the
      present was seen as an instrument affording access to the past, reconstruction of
      which would free the patient from the repetition compulsion, nowadays the past is
      regarded more as a means of throwing light on the present and the emphasis has
      shifted to the here and now, the unconscious meanings of which are elucidated by
      the analyst's careful monitoring of his own mental states. In transference
      analysis in the here and now, what is analysed today, in the current revised
      conception of the analyst's role, is the interaction between patient and analyst.
      The author notes that the concept of interaction did not feature in the theory
      and clinical practice of classical psychoanalysis, according to which the
      analytic dialogue was supposed to be confined to verbal exchanges. Yet the
      interactive dimension is of course present in the 'pragmatic' elements of the
      linguistic communication, whereby patient and analyst influence each other, and
      can be analysed by constant, spontaneous unconscious-preconscious monitoring of
      the analytic relationship. Clinical material is presented to illustrate the
      examination and use of the pragmatic aspects of the patient-analyst interaction.
      The analyst is shown in the process of analysing the verbal interaction as a
      background to interpretive activity, which is in this case interpretation of
      interaction.

PMID- 9152754
TI  - A mind of one's own.
AB  - The author argues that in the transference the patient unconsciously identifies
      the analyst with what he has projected into him, creating what Strachey called an
      external phantasy object. In the intimate rapport of the analytic session, the
      analyst tends to identify with these projections as well, which brings him into a
      relationship with the patient that complements the patient's narcissistic object
      relationship with him. The analyst's identification with the patient's
      projections is a type of pathology of his receptivity to the patient that is
      exacerbated by the patient's skill at producing states of mind in the analyst
      with which the analyst is supposed to identify. The analyst's ability to distance
      himself from the patient's projections and therefore to interpret them depends on
      his having links to his internal objects that survive the patient's projections
      and unconscious manipulations. Interpretations make the patient aware
      simultaneously that he and the analyst are separate and that the analyst has a
      link to internal objects that are not under the patient's control. The latter is
      a rudimentary oedipal situation. The author argues that these two 'awarenesses'
      are really the same, and that working through the depressive position and working
      through the oedipal situation are therefore fundamentally the same thing.

PMID- 9152755
TI  - Empathy and 'empathism'.
AB  - The author begins by tracing the history of the concept of empathy in
      psychoanalysis, noting that, largely through the influence of Kohut, it began to
      feature prominently in the literature from the late 1950s on and has since
      tended, wrongly in his opinion, to be regarded as an all-purpose instrument to be
      deployed at will. What is often described in theoretical contributions as empathy
      should in the author's view more properly be called concordance. On the clinical
      level, the idea that the analyst must deliberately seek to empathise with the
      patient is stated to have gained currency, but the author argues that such an
      attempt to achieve empathy by force can lead only to 'empathism', which is a
      dogmatic, hyperconcordant attitude whereby the inexperienced analyst in
      particular thinks he can control the process better. Clinical material is
      presented to show how some patients set out to induce 'empathism' in the analyst
      for defensive reasons and how the analyst's concordance, until analysed, may lead
      to an impasse. The author stresses that genuine empathy is a state of
      complementary conscious-preconscious contact based on separateness and sharing;
      covering not only the patient's ego-syntonic subjectivity but also his defensive
      ego and split-off parts, its achievement requires prolonged hard work on the
      countertransference and a capacity for contact with the analyst's own primitive
      aspects. The paper ends with a consideration of the possible obstacles to
      empathic contact.

PMID- 9152756
TI  - The dream space and countertransference.
AB  - The author describes some similarities in the psychoanalytic literature between
      the conceptualisation of the dream space and that of the analyst's function as a
      container of the patient's projections. He also notes the correspondence between
      the creative use of a dream and the use of an analytic session to further
      understanding. Detailed clinical material is then presented from the analysis of
      two male patients, both of whom were unable to complete a dream about a
      particular emotional dilemma. The way in which they created severe disturbance in
      the countertransference at the same time is reported. The analyst's struggle to
      work through this difficulty and the beneficial consequences of this for the
      patient are described. It is argued that this demonstrates the way in which
      patients may project into the analyst dilemmas that they are unable to dream
      about in order that the analyst's functioning may transform the dilemmas into
      ones that can be thought and dreamt about. It is further argued that some
      patients have a developmental need to engage the analyst in this way.

PMID- 9152757
TI  - Self-sensuality in fantasy: reflections on early development based on a case
      history.
AB  - On the basis of a detailed account of the analysis of a severely disturbed female
      patient with suicidal tendencies and pronounced mood swings, in whom sensory
      impressions were particularly important, the author investigates the phenomena of
      hypersensuality and self-sensuality. These are shown to be closely bound up with
      the patient's primitive erotisation of both the transference and her life outside
      the analysis, their function being one of self-feeding designed to blot out the
      awareness of separation and separateness. Depending on a given subject's
      personality development and the position from which mental events are
      experienced, the author notes that this self-sensuality may be external, acted
      out or largely confined to fantasy. The case history leads to some theoretical
      reflections, supported by the results of infant observation conducted by the
      author and his assistants, on the possible connection between erotised patterns
      of relating in such patients and the existence of autistic nuclei. In the final
      part of the paper, the author considers whether the two familiar Kleinian
      positions need to be supplemented by a third, 'autistic', position, discusses the
      relevant consequences and implications, and emphasises that the assumption of the
      existence of such a position carries the risk of its reification. He ends with a
      poetic example that sums up the isolation of the patients concerned.

PMID- 9152758
TI  - Psychic reality and unconscious belief: a reconsideration.
AB  - In a recent paper Britton attempted to distinguish between a phantasy that has
      achieved the status of a belief and one that has not, and between a belief and
      knowledge. The author argues that, in the light of the seventeenth-century
      controversy between Descartes and Spinoza, both of these distinctions are
      untenable. Descartes argued, as Britton does, and as Freud did, that phantasies
      or ideas are not accepted as beliefs until they are tested against reality.
      Furthermore, Britton maintains that for a belief to acquire the status of
      knowledge, it must be supported by incontrovertible evidence. Spinoza, on the
      other hand, proposed the seemingly preposterous notion that a comprehended
      proposition is automatically believed. Doubt may subsequently be engendered by
      disconfirming evidence. As it turns out, research in a number of domains suggests
      that Spinoza was correct and Descartes was wrong. This evidence and its clinical
      implications are discussed. As suggested by Bion, instilling doubt regarding
      deeply ingrained (Spinozan-formed) phantasies is a principal goal of treatment.

PMID- 9152759
TI  - Opening remarks to a discussion of sexuality in contemporary psychoanalysis.

PMID- 9152760
TI  - The Oedipus complex, castration and the fetish: a revision of the psychoanalytic
      theory of sexuality.

PMID- 9152761
TI  - Review of the psychoanalytic theory of sexuality: comments on the assault against
      it.

PMID- 9152762
TI  - Wording and telling sexuality.

PMID- 9152763
TI  - Femininity and masculinity: clinical notes on mutual fears.

PMID- 9152764
TI  - But is Paris really burning? Uncertainty anxieties and the normal chaos of love.

PMID- 9152765
TI  - Disavowal: structural effect and pathogenic dimension.

PMID- 9152766
TI  - Sexuality, femininity, and contemporary psychoanalysis.

PMID- 9152767
TI  - Myocardial blood flow and metabolism in patients with hypertrophic cardiomyopathy
      -a study with carbon-11 acetate and positron emission tomography.
AB  - The underlying pathophysiology of hypertrophic cardiomyopathy (HCM) is still
      unclear. positron emission tomography is a suitable and promising technique for
      the detection of possible metabolic consequences of the disease. To assess
      regional myocardial blood flow and metabolism, 19 asymptomatic or only mildly
      symptomatic patients with HCM and 10 normal control subjects were studied using
      carbon-11 acetate and fluorine-18-labelled deoxyglucose (FDG) as tracers of
      myocardial blood flow (Ao), oxygen consumption (k), and exogenous glucose
      utilization. In the patients, regional Ao in the hypertrophied septum and apex
      (H) was similar to that in the nonhypertrophied free wall (N) (91.3 +/- 3.9% vs
      92.9 +/- 3.1%; p = NS). However, the k values were significantly lower in H than
      in N (0.044 +/- 0.012 vs 0.060 +/- 0.016/min, p < 0.0001). The k value in N and
      normal control subjects (0.062 +/- 0.013) was similar. Postprandial FDG uptake
      was lower in H than in N (70 +/- 16 vs 91 +/- 7%; p < 0.0001) in 16 patients and
      slightly higher in 3 patients. Fasting FDG study showed increased FDG uptake in H
      in 3 out of 13 patients, suggesting a disorder of the myocardial microvascular
      circulation. A relative decrease in hypertrophied septal and apical oxidative
      metabolism and glucose utilization without any corresponding perfusion defect
      could reflect abnormal regional aerobic metabolism in the disproportionately
      thickened myocardium in patients with HCM. This suggests that a primary
      myocardial metabolic defect might be present in patients with HCM.

PMID- 9152768
TI  - Evolution of coronary vascular tone in vasospastic angina.
AB  - In general, anginal symptoms diminish with time in patients with vasospastic
      angina. We assessed changes in coronary vascular tone (CVT) in patients with
      vasospastic angina over a 4-year period to evaluate the time course of spastic
      activity. Vasospastic angina was evaluated in 39 patients in whom occlusive spasm
      was evoked by selective intracoronary injection of ergonovine maleate (ERG-S) 48
      h after stopping all coronary vasodilator drugs. These patients had no organic
      coronary stenosis and developed no stenosis during follow-up. ERG-S was repeated
      3 times at 2-year intervals. CVT was determined at each ERG-S study using the
      equation: CVT = 1-(coronary artery diameter before ERG-S/coronary artery diameter
      after intracoronary injection of isosorbide dinitrate). Thirty-four patients
      (87%) had no angina pectoris at the second ERG-S study and 28 (72%) had none at
      the third. Coronary spasm was induced in 25 patients at the second ERG-S study
      and in 20 at the third. The overall CVT was shown to decrease at each successive
      ERG-S study (p < 0.01). There was no correlation between changes in CVT and
      anginal symptoms or the coronary spasm induction rate. These results demonstrate
      that CVT decreases over time in patients with vasospastic angina, suggesting that
      myocardial ischemia may improve spontaneously.

PMID- 9152769
TI  - Comparison of immediate and long-term outcome of percutaneous transvenous mitral
      commissurotomy in patients who have and have not undergone previous surgical
      commissurotomy.
AB  - This study compared the immediate and long-term outcome of percutaneous
      transvenous mitral commissurotomy (PTMC) in patients who had (restenosis group, n
      = 9) or had not (de novo group, n = 27) previously undergone surgical mitral
      commissurotomy. The baseline echocardiographic score, which is an index of
      deformity of the mitral valve apparatus, was significantly higher in the
      restenosis group than in the de novo group (11 +/- 3 vs 7 +/- 2, p < 0.01),
      although age, left atrial diameter, and the prevalence of atrial fibrillation
      were similar. PTMC was performed by the Inoue technique, and was abandoned in 1
      patient from the restenosis group because of failed trans-septal puncture.
      Including this patient, 3 patients (33%) in the restenosis group had a thickened
      atrial septum compared with only 1 (4%) in the de novo group. One patient in the
      de novo group developed cardiac tamponade during this procedure. In both groups,
      the mitral valve area increased significantly, but the success rate of PTMC was
      lower in the restenosis group (4/9 patients, 44%) than in the de novo group
      (22/27 patients, 81%) (p < 0.05). Twenty-six patients who had successful PTMC
      were followed up over 51 +/- 14 months. After 4 years of follow-up. 3 out of 4
      patients (75%) in the restenosis group and 3 out of 22 patients (14%) in the de
      novo group demonstrated echocardiographic restenosis (p < 0.01). Stepwise
      multivariate analysis revealed that the echocardiographic score was the only
      significant predictor of both the immediate and long-term outcome. In conclusion,
      the immediate and long-term outcome of PTMC were worse in patients who had
      undergone previous surgical mitral commissurotomy than in those who had not. This
      was mainly attributable to the difference in the severity of the valvular
      lesions. In addition, our data suggested that a thickened atrial septum, possibly
      related to surgery as well as chronic rheumatic disease, may affect the
      performance of PTMC.

PMID- 9152770
TI  - Heterogeneity of myocardial fluoro-18 2-deoxyglucose uptake in patients with
      apical hypertrophic cardiomyopathy.
AB  - We have shown that myocardial glucose metabolism is heterogeneous in patients
      with hypertrophic cardiomyopathy. It is not known, however, whether glucose
      metabolism is impaired in patients with apical hypertrophic cardiomyopathy, which
      is fairly common in Japan. We studied 7 patients with apical hypertrophic
      cardiomyopathy and 5 normal subjects using fluoro-18 2-deoxyglucose (FDG) and
      positron emission tomography (PET). We calculated regional FDG fractional uptake
      and the inter-regional coefficient of variation (CV) of FDG fractional uptake in
      the interventricular septal, anteroapical, and posterolateral regions. The
      regional FDG fractional uptake was similar in the 2 groups and among the 3
      different segments within each group. However, the inter-regional CV of FDG
      fractional uptake was increased in the anteroapical wall segment of the patient
      group compared with the control group and also with the other 2 regions in the
      patient group. The results did not differ when we studied another 5 patients and
      6 normal control subjects with a PET scanner with higher spatial resolution.
      These data suggest that myocardial glucose metabolism may be impaired in the
      anteroapical wall segment of patients with apical hypertrophic cardiomyopathy.

PMID- 9152772
TI  - Preoperative autologous blood donation and plateletpheresis in patients
      undergoing elective cardiac operations--factors that influence the need for
      homologous blood transfusion.
AB  - An increased awareness of the adverse effects of homologous blood transfusion
      prompted us to initiate a blood conservation program consisting of preoperative
      autologous blood donation and platelet-rich plasma-pheresis. We studied 120
      patients who underwent elective cardiac surgery at Aomori General Hospital
      between January 1991 and September 1994. If their hemoglobin values exceeded 12
      g/ml, 400 g of whole blood was drawn 3 times before the operation. Platelet-poor
      plasma was collected 10 days before the operation and platelet-rich plasma was
      collected the day before the operation. However, despite participation in this
      program, 42 of 120 patients (35%) required homologous blood transfusion
      perioperatively. Factors that influenced the need for homologous blood
      transfusion were identified retrospectively, with the following found to be
      significant by univariate analysis: operative procedures performed,
      cardiopulmonary bypass time, and the amount of autologous blood and autologous
      plasma donated. Although the effectiveness of our blood conservation procedure
      remains to be verified, it reduced the need for the transfusion of homologous
      blood. Thus, additional units of autologous blood are required to obviate the
      need for homologous transfusion in patients undergoing long cardiopulmonary
      bypass procedures.

PMID- 9152771
TI  - Inflammatory abdominal aortic aneurysms and atherosclerotic abdominal aortic
      aneurysms--comparisons of clinical features and long-term results.
AB  - A total of 274 patients with abdominal aortic aneurysms due to atherosclerosis
      (AAA) and 16 patients with inflammatory abdominal aortic aneurysms (IAAA) were
      reviewed to compare and contrast the clinical characteristics of the 2 groups.
      The AAA group comprised 243 men and 31 women with a mean age of 69.2 +/- 0.4
      (range 51-86) years. The IAAA group comprised 15 men and 1 woman with a mean age
      of 67.4 +/- 2.0 (range 53-81) years. Most patients with IAAA (12/16; 75.0%) had
      pain at presentation, whereas only 37 out of 274 patients (13.5%) with AAA had
      pain (p < 0.001). Fifty out of 274 patients (18.2%) with AAA were asymptomatic,
      the most common principal complaint being a pulsatile tumor, which was found in
      150 out of 274 patients (54.7%; p < 0.005 vs IAAA). Regarding laboratory findings
      of inflammation, preoperative erythrocyte sedimentation rate values were elevated
      in 15 out of 16 (93.8%) patients, and C-reactive protein values were elevated in
      13 out of 16 (81.3%) patients with IAAA. The incidence of perioperative
      complications was similar in the 2 groups. The 30-day postoperative mortality
      among AAA patients was 6.2% (17/274 cases), including 12 cases of non-ruptured
      and 5 cases of ruptured AAA; in contrast, no early deaths occurred among patients
      with IAAA. The cumulative 5-year survival rate was 80.2% for IAAA patients and
      74.6% for AAA patients (NS). The results of our review suggest that careful
      diagnosis and intra- and postoperative management could lead to patients with
      IAAA having a similar survival rate to those with AAA.

PMID- 9152773
TI  - Role of platelets in myocardial ischemia-reperfusion injury in dogs.
AB  - We investigated the involvement of circulating platelets in myocardial ischemia
      reperfusion injury in canine autoperfused heart-lung preparations using filters
      to deplete platelets and/or leukocytes. The left anterior descending (LAD)
      coronary artery was occluded for 40 min, followed by 40 min reperfusion, in 3
      groups: a leukocyte-platelet-depleted (LPD) group, in which both leukocytes and
      platelets were depleted; a leukocyte-depleted (LD) group, in which leukocytes
      alone were depleted; and a control group. There were no differences in
      hemodynamics or arrhythmias among groups before or during coronary occlusion.
      After reperfusion, the maximum rate of change in left ventricular pressure during
      systole and diastole was significantly higher in the LPD group than in the
      control and LD groups. The LPD group also showed gradual recovery of regional
      myocardial function and a decrease in the frequency of premature ventricular
      contractions. The LD group showed a slight improvement in cardiac function and
      arrhythmias compared with the control group. Although there was no significant
      difference in the pulmonary arterial plasma level of thromboxane B2 at any stage
      among groups, the control group showed an increase after reperfusion. These
      results suggest that platelets are important in reperfusion injury and that the
      depletion of both leukocytes and platelets effectively protects against
      reperfusion injury.

PMID- 9152774
TI  - Abnormal beta-adrenergic transmembrane signaling in rabbits with adriamycin
      induced cardiomyopathy.
AB  - We investigated alterations in the beta-adrenergic receptor-adenylate cyclase
      system in rabbits with congestive heart failure induced by adriamycin
      cardiotoxicity. A dose of 24 mg/kg adriamycin was administered over 16 weeks in
      16 rabbits. Five of them died and 4 of them could not tolerate the full dose of
      adriamycin. Complete data were obtained in the remaining 7 rabbits. Another 7
      rabbits received physiological saline for the same period and served as controls.
      Plasma norepinephrine concentration increased in adriamycin-treated rabbits, but
      not in the control rabbits. Cardiac output was lower in the adriamycin-treated
      group than in the control group. Both the left and right ventricular end
      diastolic pressure were higher in the adriamycin-treated group. The density of
      myocardial beta-adrenergic receptors and the norepinephrine content were reduced
      in both ventricles in the adriamycin-treated group. Basal and isoproterenol-,
      sodium fluoride- and forskolin-stimulated adenylate cyclase activities were lower
      in the adriamycin-treated group. Thus, alterations in beta-adrenergic signaling
      occurred in both ventricles in animals with chronic biventricular failure induced
      by adriamycin. These may be the result of post-receptor abnormalities, including
      abnormalities of guanine nucleotide-binding proteins or of the catalytic unit of
      adenylate cyclase.

PMID- 9152776
TI  - Absence of myocardial 123I-BMIPP uptake in the presence of a normal coronary
      angiogram and normokinetics on a left ventriculogram.
AB  - We present the case of a 44-year-old man with abnormal myocardial fatty acid
      metabolism who exhibited no myocardial uptake of 123I-beta-methyl- iodophenyl
      pentadecanoic acid (123I-BMIPP). This patient presented to our hospital with an
      ECG abnormality detected during a medical check-up. He felt no chest discomfort,
      but a 12-lead ECG at rest showed flat T-waves in leads I, V5, and V6 with no
      marked ischemic changes during exercise. A left ventriculogram and coronary
      angiograms were normal. Thallium-201 single photon emission computed tomography
      imaging revealed a normal myocardial uptake, but 123I-BMIPP imaging showed no
      such uptake. However, 18F-labelled fluorodeoxyglucose positron emission
      tomography imaging after an overnight fast showed a marked increase in myocardial
      uptake. It appears that myocardial uptake of 123I-BMIPP was totally lacking and
      that energy production by the myocardium during fasting depended on the
      metabolism of glucose rather than of fatty acids.

PMID- 9152775
TI  - Effects of locally administration of argatroban using a hydrogel-coated balloon
      catheter on intimal thickening induced by balloon injury.
AB  - The purpose of this study was to evaluate the inhibitory effects of locally
      delivered argatroban, a competitive inhibitor of thrombin-induced platelet
      activation, on intimal proliferation after balloon injury. A hydrogel-coated
      balloon catheter was immersed 3 times in an argatroban/saline solution (1, 0.1,
      or 0.01 mg/ml) for 60 s and inflated at 6 atm pressure for 1 min in the rabbit
      common carotid artery. Immersion in a saline solution without drug followed by
      the same procedure served as a control. Accumulation of argatroban in the
      vascular wall was confirmed by chemical determination using high-performance
      liquid chromatography (HPLC). The concentration of argatroban in the vessel wall
      immediately after deflation after balloon immersion in solutions of 1 and 0.1
      mg/ml was 14.8 +/- 10.9 and 5.5 +/- 4.6 nmol/g wet weight of artery,
      respectively. Argatroban was not detected in arteries treated with a balloon that
      had been immersed in the 0.01 mg/ml argatroban/saline solution. Intima-media area
      ratios 20 days after balloon injury in the groups treated with 1 mg/ml (n = 8)
      and 0.1 mg/ml (n = 6) agratoban were significantly smaller than that in the
      groups treated with 0.01 mg/ml (n = 7) argatroban or saline (n = 8) (0.35 +/-
      0.11, 0.50 +/- 0.17, 1.24 +/- 0.39, and 1.35 +/- 0.43, respectively; p < 0.001).
      These data suggest that locally administered argatroban dose-dependently inhibits
      intimal thickening in a rabbit model of carotid artery injury.

PMID- 9152777
TI  - Exercise-induced second-degree atrioventricular block.
AB  - In this report we describe 2 patients with exercise-induced, second-degree
      atrioventricular (AV) block. Case 1 was a 49-year-old man with normal AV
      conduction at rest but who developed dyspnea on exertion. Treadmill testing
      showed an exercise-induced 2:1 AV block. Electrophysiologic study (EPS)
      demonstrated rate-dependent, presumably intrahissian, AV block. Case 2 was a 31
      year-old woman with first-degree AV block and complete right bundle branch block
      with dyspnea on exertion and occasional syncope. She had twice undergone surgical
      patch closure of an ostium primum atrial septal defect. Exercise testing induced
      type II second-degree AV block. Atrial pacing during EPS did not disclose rate
      dependent type II AV block, but disopyramide induced second-degree AV block.

PMID- 9152778
TI  - Idiopathic restrictive cardiomyopathy with diffuse perimyocytic fibrosis--a rare
      observation.
AB  - Idiopathic restrictive cardiomyopathy (RCM) is rare. Even today little is
      understood of its etiology or underlying mechanisms, and definitive diagnostic
      criteria are lacking. In this report, we describe a case of idiopathic RCM in a
      young Japanese woman who died while awaiting cardiac transplantation during the 5
      year course of the disease. Rare pathologic findings of diffuse perimyocytic
      fibrosis were revealed at autopsy.

PMID- 9152779
TI  - Molecular and immune mechanisms in the pathogenesis of cardiomyopathy--role of
      viruses, cytokines, and nitric oxide.
AB  - Myocarditis is thought to be commonly caused by various viruses, and accumulating
      evidence links viral myocarditis with the eventual development of dilated
      cardiomyopathy. Recently, the importance of hepatitis C virus infection was noted
      in patients with dilated and hypertrophic cardiomyopathy. Cytokines are being
      increasingly recognized as an important factor in the pathogenesis and
      pathophysiology of myocarditis and cardiomyopathy. Elevated levels of circulating
      cytokines have been reported in patients with heart failure, and various
      cytokines have been shown to depress myocardial contractility in vitro and in
      vivo. A number of reports have shown that cytokines generated by activated immune
      cells cause an increase in nitric oxide (NO) via induction of NO synthase.
      Increased generation of NO may induce negative inotropism and myocardial damage.
      This review discusses the etiology and pathogenesis of myocarditis and
      cardiomyopathy from this point of view.

PMID- 9152780
TI  - Relation between the initial portion of the signal-averaged QRS complex and
      cardiac function and infarct size in patients with myocardial infarction.
AB  - We analyzed signal-averaged electrocardiograms (ECG) obtained in 50 patients with
      recent myocardial infarction (RMI: 25 anterior and 25 inferior) and 20 normal
      subjects to determine the relationship between the initial portion of the signal
      averaged QRS complex and cardiac function and infarct size. We examined (1) the
      root mean square voltage (RMS10-40, microV), (2) the integration (A10-40,
      microV.msec) at 10-msec intervals over the first 40 msec of the signal-averaged
      QRS complex, and (3) the intervals (T) of the magnitude of the signal-averaged
      ECG achieved at 10-microV intervals over the first 40 microV (T10-40, msec). The
      mean RMS10-40 (p < 0.01) and A10-40 (A10, p < 0.05; A20-40, p < 0.01) were
      significantly lower and the T10-40 (p < 0.01) was significantly longer in RMI
      patients than in normal subjects. The RMS10-40 (p < 0.01) and A10-40 (p < 0.05)
      were significantly lower and the T10-40 (T10.20, p < 0.01; T30.40, p < 0.05) was
      significantly longer in patients with anterior RMI patients than in patients with
      inferior RMI. The A30 was correlated with the ejection fraction and total
      creatine kinase (CK) release in all patients (r = 0.73, and -0.78, respectively,
      p < 0.001). These results suggest that the A30 may be an important predictor of
      ventricular dysfunction and infarct size in patients with RMI.

PMID- 9152781
TI  - Angina pectoris after recovery from an acute coronary event--the role of
      psychological factors in Japanese vs North American patients.
AB  - To determine whether specific psychological characteristics are associated with
      angina pectoris in clinically stable patients 1 to 6 months after recovery from
      an acute coronary event, a battery of tests was administered to 92 Japanese and
      646 North American participants (22% females) in the Multicenter Study of
      Myocardial Ischemia. Of these 738 patients, 541 had originally suffered acute
      myocardial infarction, 188 had unstable angina, and 9 were admitted for other
      acute ischemic events. At the time of enrollment, an average of 2.7 months after
      the index event, 205 patients reported having had anginal symptoms during the
      preceding months. Compared to those who did not report angina, these patients
      scored higher on a modified Autonomic Perception Questionnaire (p = 0.04) and
      lower on the Internal Health Locus of Control Scale (p = 0.004). These
      differences were generalized across the Japanese and North American cohorts.
      These results indicate that in these patients, angina pectoris was associated
      with an increased awareness of a wide range of physical symptoms and a decreased
      sense of personal control over one's own health and prognosis.

PMID- 9152782
TI  - Captopril reduced plasminogen activator inhibitor activity in patients with acute
      myocardial infarction.
AB  - Recent clinical trials have demonstrated that the administration of angiotensin
      converting enzyme (ACE) inhibitors to patients with myocardial infarction reduces
      the incidence of recurrent myocardial infarction. It has also been reported that
      an elevated level of plasminogen activator inhibitor (PAI) appears to constitute
      a marker of the risk of recurrent coronary thrombosis. To determine whether the
      ACE inhibitor captopril reduces plasma PAI inhibitor activity, we measured
      changes in plasma PAI activity (IU/ml), tissue plasminogen activator (t-PA)
      antigen (ng/ml), and serum ACE activity (IU/L) in 14 survivors of myocardial
      infarction receiving captopril therapy (37.5 mg daily) and compared them with the
      values in 15 placebo-treated patients chosen at random. Blood sampling was
      performed at 07.00 h. In the captopril-treated group, serum ACE activity
      decreased significantly, from 14.0 +/- 0.8 to 11.5 +/- 1.2 IU/L 24 h after
      captopril therapy (p < 0.01), and those of PAI activity and t-PA antigen also
      decreased significantly-from 11.9 +/- 2.8 to 5.5 +/- 2.2 IU/ml (p < 0.02) and
      from 9.9 +/- 1.0 to 7.5 +/- 0.9 ng/ml (p < 0.05), respectively 48 h after
      captopril therapy. However, the levels of ACE activity, PAI activity, and t-PA
      antigen remained unchanged during the study period in the placebo group. Thus,
      our data indicate that the administration of captopril to patients with acute
      myocardial infarction may result in a reduced frequency of recurrent coronary
      thrombosis by increasing fibrinolytic capacity.

PMID- 9152783
TI  - Use of serum creatine kinase MM isoforms for predicting the progression of left
      ventricular dilation in patients with hypertrophic cardiomyopathy.
AB  - Serum creatine kinase (CK) isoforms were examined to detect the progression of
      left ventricular (LV) enlargement with reduced motion, resembling dilated
      cardiomyopathy (DCM), in hypertrophic cardiomyopathy (HCM). Changes in LV indices
      were determined annually by echocardiography in 51 patients until serum
      measurements (first follow-up period, 6.5 +/- 2.2 years). Serum creatine isoforms
      (CKMM1, CKMM2 and CKMM3) were measured with high-voltage electrophoresis in 35 of
      these patients from 1991 to 1992, and the data for these latter patients are
      reported here. Serum total CK, CKMB, lactate dehydrogenase and its isoenzyme LDH1
      were also measured. The changes in LV indices were further monitored until
      January, 1995 (second follow-up). During the 2 follow-up periods, the patients in
      the on-going group showed a reduction in the LV ejection fraction (LVEF) to < 55%
      with LV end-diastolic dimension (LVDd) < 55 mm, and those in the DCM-like group
      showed a reduction in LVEF to < 55% and an increase in LVDd to > 55 mm. During
      the first follow-up period, LVEF and LVDd remained at > or = 55% and < 55 mm,
      respectively, in 26 patients (nonprogressive-disease group), while 3 patients
      entered the on-going group and 6 entered the DCM-like group. The CKMM3/CKMM1
      ratios in the on-going and DCM-like groups were significantly higher than those
      in the control and nonprogressive-disease groups. The CKMM3/CKMM1 ratio was
      significantly correlated with the annual rate of change for the LV end-systolic
      dimension (LVDs), LVDd, and LVEF, with the closest correlation observed for the
      annual change in LVDs. Moreover, 5 patients in the nonprogressive-disease group
      with elevation of the CKMM3/CKMM1 ratio to > + 2SD above the mean for the
      controls had an elevated annual change in LVDs within +/- 1SD of the mean in the
      DCM-like group. These results indicate that the ratio of CKMM3 to CKMM1 can be
      used to predict the progression of LV enlargement in HCM.

PMID- 9152784
TI  - Effects of adenosine triphosphate on ventriculoatrial conduction--usefulness and
      problems in assessment of catheter ablation of accessory pathways.
AB  - The effects of adenosine triphosphate (ATP) on ventriculoatrial (VA) conduction
      were examined before and after accessory pathway (AP) ablation, with emphasis on
      assessment of the complication of dual atrioventricular (AV) node pathway. By
      evaluating the differences in the response to ATP of APs and other pathways, we
      assessed the usefulness and problems of this method. Of 59 patients who underwent
      AP ablation, 31 showed pre-excitation and 28 had concealed APs. A dual AV node
      pathway was found in 9 patients (15.3%) before ablation. After ablation, a dual
      AV node pathway was newly found in 9 patients. Thus, the total number of patients
      with a dual AV node pathway was 18 (30.5%). VA conduction over APs was not
      blocked in 26 of 29 patients, but the remaining 3 APs were blocked transiently by
      ATP. ATP caused VA block over the AV node in 15 of 16 patients and a dual AV node
      pathway in all 11 patients. In contrast, VA conduction over the retrograde fast
      pathway was blocked in 9 of 14 patients with AV node re-entrant tachycardia. ATP
      has little effect on APs, so observation of the response to ATP provides a more
      reliable and useful means of evaluating successful ablation. With this method,
      however, it is important to consider the possibility of the presence of ATP
      sensitive APs and ATP-resistant retrograde fast pathways. The influence of
      ablation-induced injury has not been fully clarified. It is therefore essential
      to take into account various data, including the comparison between data obtained
      before and after ablation.

PMID- 9152785
TI  - Heart disease deaths on death certificates re-evaluated by clinical records in a
      Japanese city.
AB  - In order to estimate the number of deaths from ischemic heart disease (IHD) in a
      Japanese city, we reevaluated heart disease deaths among residents aged 25-74
      years by examining their clinical records. During the 2-year period from 1987 to
      1988, 271 deaths among this population were attributed to heart disease. The
      recorded underlying cause of death was IHD in 96 cases, heart failure in 123
      cases, and other heart disease in 52 cases. Re-evaluation of the cause of death
      yielded 57 cases of acute myocardial infarction (AMI), 85 cases of sudden death,
      37 cases of heart disease other than IHD, and 63 cases of non-heart disease. In
      the remaining cases, there was insufficient information for evaluation. According
      to some autopsy studies, about 50% of sudden deaths are due to IHD. Thus, 50% of
      the number of sudden death cases may be added to the total number of IHD deaths.
      Accordingly, the total number of IHD deaths may have been 100, ie, 57 cases of
      AMI plus 43 cases of sudden death. The difference between the number of IHD
      deaths after re-evaluation and the number for which IHD was recorded as the
      underlying cause was small, with the former only 4% higher than the latter. The
      number of false-positives was equal to the number of false-negatives, and hence
      the number of IHD deaths recorded in this area seems to be close to the actual
      figure. We speculate that more accurate death certification will result in a
      decrease in the total number of deaths attributable to heart disease, as in 23%
      of deaths attributed to heart disease the underlying cause of death was not in
      fact heart disease.

PMID- 9152786
TI  - Relationship between left ventricular diastolic function at rest and exercise
      capacity in patients who have suffered a previous myocardial infarction.
AB  - To assess whether left ventricular (LV) diastolic function is a determinant of
      exercise capacity in patients who have suffered a previous myocardial infarction
      (MI), we investigated the relationship between maximum exercise duration and
      resting LV diastolic function in 65 MI patients. Each patient underwent both a
      symptom-limited exercise test and LV biplane angiography with simultaneous high
      fidelity pressure measurements. LV relaxation was assessed by the time constants
      (T1/e and T1/2) of isovolumic pressure decay, and LV diastolic distensibility was
      assessed by the LV end-diastolic volume (V) index-pressure (P) ratio. The time
      constants of relaxation did not correlate with maximum exercise capacity (r = 
      0.19 for T1/e, NS; r = - 0.17 for T1/2, NS). LV diastolic distensibility also did
      not correlate with exercise capacity (r = - 0.08, NS). These results suggest that
      the resting LV diastolic dysfunction is unlikely to be the principal cause of
      exercise intolerance in MI patients without congestive heart failure.

PMID- 9152787
TI  - Preconditioning with 15-minute ischemia extends myocardial infarct size after
      subsequent 30-minute ischemia in rabbits.
AB  - Ischemic preconditioning (PC) induced by 1 cycle of 5-min coronary occlusion and
      5-min reperfusion limits infarct size (IS) after 30-min sustained ischemia in
      rabbits. The shortest ischemic period that induces the PC effect in rabbits is 3
      min. To establish the maximum ischemic period to induce a beneficial PC effect,
      we examined the effect of PC periods of 10 and 15 min on IS after sustained
      ischemia. The IS in control rabbit hearts after 30 min of sustained occlusion of
      the left anterolateral coronary artery and 48-h reperfusion was compared with
      that of hearts treated as follows before being subjected to PC: 5-min occlusion
      and 5-min reperfusion; 10-min occlusion and 5-min reperfusion; or 15-min
      occlusion and 5-min reperfusion. In addition, the IS after 15-min or 45-min
      occlusion and 48-h reperfusion was measured. There was no significant difference
      in blood pressure, heart rate, or area at risk (AAR) among the rabbits in 5
      groups. The IS measured histologically was 40 +/- 4% of AAR in the control, 10 +/
      3% after 5-min PC, and 12 +/- 2% after 10-min PC. However, in the 15-min PC
      group, the IS was 77 +/- 4% of AAR, which was significantly larger than that of
      the controls, but similar to that of hearts subjected to 45-min ischemia and
      reperfusion (67 +/- 3%). As 15 min of preconditioning ischemia alone caused small
      infarcts (18 +/- 1% of AAR), the infarcts caused by sustained ischemia per se in
      the 15-min PC group was estimated to be 72 +/- 5% of AAR, which was still
      significantly higher than in the control groups. We conclude that the maximum
      period of preconditioning ischemia that induces cardioprotection in rabbits is 10
      min. When the ischemic period is longer than this, the IS after sustained
      ischemia is increased rather than restricted. However, the infarcted size in the
      15-min PC group was not higher than that in the group subjected to 45-min
      continuous ischemia. This may be a major limitation for any clinical application
      of PC.

PMID- 9152788
TI  - A case of dilated cardiomyopathy with abnormal atrioventricular conduction 5
      years before the appearance of left ventricular systolic dysfunction.
AB  - The first manifestation of dilated cardiomyopathy is usually dyspnea as a result
      of left heart failure. In this report we describe an unusual patient with third
      degree atrioventricular (AV) block unaccompanied by left ventricular dysfunction.
      Severe left ventricular dysfunction occurred 5 years after the implantation of a
      permanent pacemaker. We conclude that AV block should not be overlooked as an
      initial clinical manifestation of dilated cardiomyopathy.

PMID- 9152789
TI  - Traumatic tricuspid regurgitation associated with congenital partial pericardial
      defect.
AB  - Traumatic tricuspid regurgitation (TR) and congenital pericardial defects are
      rare conditions, there being fewer than 200 recorded cases of each. Here we
      describe the interesting case of a patient with traumatic TR due to rupture of
      chordae tendineae in association with a congenital pericardial defect. We suggest
      that the association of traumatic TR and congenital pericardial defect has a high
      probability of occurrence. We hypothesize that traumatic rupture of valvular
      structures occurs readily in patients with congenital pericardial defects.

PMID- 9152790
TI  - A case of amiodarone-induced thyrotoxicosis successfully treated with
      prednisolone.
AB  - We describe a patient who was treated with amiodarone for ventricular arrhythmia
      based on arrhythmogenic right ventricular dysplasia and who subsequently
      developed severe amiodarone-induced thyrotoxicosis. Discontinuation of amiodarone
      resulted in sustained ventricular tachycardia, which was successfully treated
      with a DC electrical shock, and subsequently atrial fibrillation, leading to
      brain embolism due to occlusion of the left middle cerebral artery. Combination
      treatment with amiodarone and prednisolone was effective both in reducing the
      serum concentration of thyroid hormones and in improving the patient's general
      condition. As the use of amiodarone becomes more widespread, treatment with
      prednisolone for this kind of thyrotoxicosis, which is resistant to conventional
      treatment, will be required increasingly frequently because iodine overload of
      the thyroid gland persists for some time after discontinuation of amiodarone
      treatment.

PMID- 9152791
TI  - Temporal relationship between cancers of the lung and upper aerodigestive tract.
AB  - We retrospectively reviewed the chart records at the Veterans General Hospital
      Taipei for the period between January 1985 and December 1994 to examine the
      temporal relationship between cancers of the lung and upper aerodigestive tract.
      A total of 56 patients (54 males, 2 females) with histocytologically proven
      double primary cancers, with either lung cancer or upper aerodigestive tract
      cancers appearing first, were found. Squamous cell carcinoma was the most
      frequent histologic type of lung cancer (squamous 57%, adenocarcinoma 27%, poorly
      differentiated carcinoma 9%, small cell lung cancer 7%). The incidence of lung
      cancer patients with upper aerodigestive tract cancer was 0.9% (56/6412). There
      was no significant difference in the occurrence of upper aerodigestive tract
      cancer between non-small cell and small cell lung cancer (P > 0.05). However, the
      incidence of squamous cell lung cancer with upper aerodigestive tract cancer was
      higher than that of non-squamous cell lung cancer (P < 0.05). With regard to the
      location of lung cancer, the right lung was more commonly affected than the left
      (P < 0.001). The locations of upper aerodigestive tract cancers in these lung
      cancer patients were as follows: larynx 24, nasopharynx 11, esophagus 10,
      hypopharynx 4, pharyngeal tonsils 2, oral cavity 5. Most upper aerodigestive
      tract cancers were diagnosed before lung cancer (36/56, 64%), and lung cancer was
      diagnosed within 3 years in more than half of cases after the diagnosis of upper
      aerodigestive tract cancer (58.3%). Most lung cancers that preceded upper
      aerodigestive tract cancer were at an early stage at diagnosis (stage I 4, stage
      Illa 1), whereas the others, appearing either synchronously or after the
      diagnosis of upper aerodigestive tract cancer, were mostly at the late stage.
      There was no difference in survival between lung cancer patients with upper
      aerodigestive tract cancer and those without (P > 0.05).

PMID- 9152792
TI  - Comparison of clinical features and survival in patients with hepatitis B and C
      virus-related hepatocellular carcinoma.
AB  - We analyzed the clinical characteristics and survival of 185 patients with
      hepatitis B virus-related hepatocellular carcinoma (HBV group) and 1033 with
      hepatitis C virus-related hepatocellular carcinoma (HCV group) by multi center
      study. The patients in the HBV group (mean age 52.1 yr) were about 10 years
      younger than those in the HCV group (mean age 62.9 yr). Liver function, as
      measured by indocyanine green retention at 15 min, was better in the HBV group
      (17.5%) than in the HCV group (25.4%). A higher proportion of the HBV group (55%)
      than the HCV group (44%) had clinical stage I, T-factor differed significantly
      between the groups: 53% of the HBV group were T3-4 compared with 41% of the HCV
      group. Furthermore, a higher proportion of the HBV group were graded 2-3 for
      tumor thrombus in the portal vein (20.3%) and had poorly differentiated
      hepatocellular carcinoma (7%) compared with the HCV group (7.1% and 5%
      respectively). Univariate analysis identified poor prognostic factors for
      hepatocellular carcinoma as HBV, age < or = 50 yr, clinical stage II-III, a high
      AFP level, higher number of tumors, larger tumor size, tumor thrombus in the
      portal vein 2-3 and in the hepatic vein 2-3. On multivariate analysis, poor
      prognostic factors were a high AFP level, higher number of tumors, tumor thrombus
      in the portal vein 2-3 and in the hepatic vein 2-3, but not HBV, age, clinical
      stage or tumor size. These results suggest that HBV itself is not a stronger
      prognostic factor than HCV.

PMID- 9152793
TI  - Urinary continence following radical prostatectomy.
AB  - An examination was made of pre- and postoperative variables for predicting
      urinary continence following radical prostatectomy in 94 consecutive patients.
      Postoperative recovery of urinary continence continued for up to 18 months, when
      it plateaued. No pads were required in 73.0% of the patients at 18 months. The
      interval until recovery of urinary continence following surgery averaged 4.0 +/-
      3.3 months. Clinical stage, pathologic stage, tumor grade, tumor volume,
      preservation of neurovascular bundles, methods of bladder neck reconstruction,
      internal urethrotomy for anastomotic stricture and postoperative adjuvant
      external beam radiation therapy provided no indication of postoperative urinary
      incontinence. Preoperative endocrine therapy, preoperative prostate-specific
      antigen level of > or = 10.0 ng/ml and age < 70 years at the time of surgery were
      all associated with a greater probability of urinary incontinence. Multiple
      factors are involved in the etiology of postprostatectomy urinary incontinence.
      In patients who had undergone surgery because of local progression following
      endocrine therapy associated with a high serum prostate-specific antigen level, a
      significantly inferior outcome was noted. Stricter criteria for indicating
      radical prostatectomy in patients with prostate cancer are needed. Surgical
      techniques should also be improved for better overall continence.

PMID- 9152794
TI  - Phase II study of ifosfamide and etoposide chemotherapy for extensive-disease
      small-cell lung cancer.
AB  - We conducted a phase II study of ifosfamide and etoposide chemotherapy in
      patients with untreated extensive-disease small-cell lung cancer to assess
      response and toxicity. Between January 1994 and December 1995, 16 patients were
      treated. Ifosfamide and etoposide doses were ifosfamide 2 g/m2, with mesna, i.v.
      infusion over 30 minutes on days 1-3 and etoposide 80 mg/m2 i.v. over 120 minutes
      on days 1-3 every 4 weeks for up to six cycles. All patients were evaluable for
      toxicity profile and treatment response. As expected, the major toxicity was
      myelosuppression. With one exception, grade 3 or 4 leukopenia occurred in all
      patients during treatment, and 48.7% of the total courses had grade 3 or 4
      leukopenia. Nine of 16 patients (56.3%) experienced episodes of febrile
      neutropenia. One toxic death due to febrile neutropenia with sepsis was
      documented. Toxicities other than leukopenia were few and mild in severity. After
      two cycles of treatment, the overall response rate was 81.3% (95% confidence
      interval 62.2-100) in this study. The median duration of response was 8 months
      and median survival was 11 months. In conclusion, ifosfamide and etoposide is an
      active combination regimen with acceptable toxicity profile in Chinese patients
      with extensive-disease small-cell lung cancer.

PMID- 9152795
TI  - A preliminary study on the emotional distress of patients with terminal-stage
      cancer: a questionnaire survey of 1380 bereaved families over a 12-year period.
AB  - To clarify the emotional distress of terminal cancer patients, questionnaires
      were sent to 2826 families of patients who died at the National Kyushu Cancer
      Center; 1380 replies were obtained. Among the 1380 patients, 37.7% had been aware
      of the disease name and 19.8% had been unaware. Of the 1380 patients, 43.5% had
      prepared for and calmly accepted death, but 12.4% had greatly feared and 11.7%
      rejected death. Patients aware of the disease name had tended to prepare better
      for death but also had a stronger fear compared with those who were unaware.
      Patients informed of the exact nature of their disease by their physicians tended
      to value their remaining life more than those informed by others. Those who had
      desired notification of the disease name also tended to value their remaining
      life more than those who had not. They also spent their remaining life more
      usefully, and were less discouraged after being informed than those who had not
      expressed a wish to be informed. Thus: 1. The emotional state of the cancer
      patient should be clearly established before deciding to inform the patient of
      the true diagnosis. 2. The patient should be notified of the disease by the
      doctor, even if he/she is already aware of the diagnosis through others. 3. The
      ability to share bad news with the patient is of crucial importance for
      physicians when caring for terminal- stage cancer patients.

PMID- 9152796
TI  - Malignant lymphoma in patients with rheumatic diseases other than Sjogren's
      syndrome: a clinicopathologic study of five cases and a review of the Japanese
      literature.
AB  - We conducted clinicopathologic and immunohistochemical analysis of five patients
      with malignant lymphoma complicating rheumatic diseases other than Sjogren's
      syndrome, and reviewed 26 cases of similar lesions reported in the Japanese
      literature over a 17-year period. All five patients were women ranging in age
      from 31 to 74 years (mean 55 years). Two of them fulfilled the diagnostic
      criteria for systemic lupus erythematosus, two for dermatomyositis and one for
      progressive systemic sclerosis. The use of immunosuppressive drugs before the
      onset of malignant lymphoma was recorded in four patients. All the biopsied or
      resected specimens showed non-Hodgkin's lymphoma of B-cell phenotype. Three were
      nodal in origin (one diffuse mixed, one diffuse large cell and one immunoblastic)
      and two were extranodal (one low-grade B-cell lymphoma of mucosa-associated
      lymphoid tissue and one diffuse large cell). In three of four cases examined,
      Epstein-Barr virus-encoded small RNAs were identified in a small to large number
      of the lymphoma cells by in situ hybridization. Our study showed that the
      clinicopathological features of malignant lymphomas complicating rheumatic
      disease in Japan were similar to those in England and the USA. Furthermore, our
      findings suggested no evidence for a causative association between iatrogenic
      immunosuppression due to methotrexate therapy and the development of EBV-related
      lymphoid neoplasms.

PMID- 9152797
TI  - A case of angiosarcoma of the breast.
AB  - This is a case report of a 20-year-old woman who had primary angiosarcoma of the
      left breast, with metastases to the spleen and ovary. Eight months after
      detecting a mass in her breast, she underwent mastectomy with biopsy of the
      ipsilateral axillary lymph nodes, splenectomy and bilateral oophorectomy. Five
      months after the operation, the patient succumbed to lung metastases.
      Angiosarcoma of the breast is a rare condition with a poor prognosis, and there
      are no established chemotherapeutic regimens as yet. Immunohistochemical staining
      for endoglin, known to be expressed mainly on the surface of endothelial cells,
      was positive. This suggests the possibility of treating angiosarcoma with anti
      endoglin monoclonal antibodies.

PMID- 9152798
TI  - Small cell carcinoma of the esophagus: a case report.
AB  - This article reports a case of primary undifferentiated small cell carcinoma of
      the esophagus with lymph node metastasis which invaded the stomach wall. The
      patient was treated with chemotherapy alone, consisting of CDDP and VP-16. The
      patient had a complete response to chemotherapy, with no evidence of disease for
      nine months, after six courses of the regimen. Small cell carcinoma of the
      esophagus is an aggressive tumor with an extremely poor prognosis. Because its
      characteristics are similar to small cell carcinoma of the lung, small cell
      carcinoma of the esophagus should be treated by multi-drug chemotherapy including
      CDDP, with or without radiation as the first line treatment. This chemotherapy
      regimen may achieve a long disease-free survival time.

PMID- 9152799
TI  - Clinicopathological studies on coexisting gastric malignant lymphoma and gastric
      adenocarcinoma: report of four cases and review of the Japanese literature.
AB  - Among 121 cases of primary gastric malignant lymphoma from 1962 to 1994 at the
      National Cancer Center Hospital, Tokyo, we found four cases (three males and one
      female) of adenocarcinoma coexisting in the stomach. The incidence of gastric
      malignant lymphoma together with gastric adenocarcinoma was 3.3%, suggesting that
      patients with lymphoma may have an increased incidence of gastric adenocarcinoma.
      A review of the Japanese literature revealed an additional 62 patients who
      developed coexisting gastric malignant lymphoma and adenocarcinoma. In the total
      series of 66 patients whose age and sex were recorded, there were 48 males with a
      mean age of 63.8 years and 18 females with a mean age of 58.6 years. Most
      adenocarcinomas were macroscopically early (76%) and of histologically
      differentiated type (75%). Conversely, 71% of lymphomas were of the advanced type
      macroscopically. The correct preoperative diagnoses were made in only 27% (16/59)
      of cases, when both tumors were located independently.

PMID- 9152800
TI  - Bellini duct carcinoma: a case report.
AB  - We report a rare case of Bellini duct carcinoma, which is an unusual variant of
      renal cell carcinoma. The patient, a 56-year-old man, was admitted to our
      hospital for detailed examination of a renal mass on the left side. He had no
      clinical symptoms such as gross hematuria or flank pain. Abdominal
      ultrasonography, computed tomography and magnetic resonance imaging revealed a
      tumor 4 cm in diameter at the lower pole of the left kidney. Selective renal
      angiography showed an avascular mass lesion. We performed left transperitoneal
      radical nephrectomy with a preoperative diagnosis of left renal tumor, T2N0M0.
      The histopathological diagnosis was Bellini duct carcinoma of papillary tubular
      type. Lectin histochemistry demonstrated positive staining with soyabean
      agglutinin and peanut agglutinin. These findings supported our conclusion that
      the tumor might have originated from the Bellini duct epithelium. The patient
      currently remains disease-free. The pathogenesis and management of this rare
      condition are discussed.

PMID- 9152801
TI  - Colonoscopy for frank bloody stools associated with cancer chemotherapy.
AB  - Diarrhea is a common complication of cancer chemotherapy, while bloody stool is
      rare. Pseudomembranous colitis has been reported as causing bloody diarrhea after
      chemotherapy. In this report, we describe nine consecutive patients who presented
      frank bloody stools within one month after cancer chemotherapy. Patients with a
      history of pelvic irradiation or with a previously identified colorectal tumor
      were excluded. Among nine patients, bleeding from tumor undetected before
      chemotherapy was seen in three, pseudomembranous colitis in four, ischemic
      colitis in one and methicillin-resistant Staphylococcus aureus enterocolitis in
      one. Of the three tumors, one was an adenomatous polyp and the other two were
      metastatic tumors. Two of the four patients with pseudomembranous colitis had not
      received antibiotics before the onset of colitis. Causes of bloody stools after
      chemotherapy were various and colonoscopy played an important role in diagnosis
      and prompt therapy.

PMID- 9152802
TI  - Mitomycin-C induced hemolytic uremic syndrome: a case report and literature
      review.
AB  - Hemolytic uremic syndrome spontaneously arises in a few patients with advanced
      cancer, but it is more commonly related to the use of certain chemotherapeutic
      agents. Mitomycin-C is, etiologically, the most common causative agent inducing
      hemolytic uremic syndrome, in a dose dependent manner. We report this syndrome,
      attributable to mitomycin-C at a cumulative dose of 40 mg/m2, in a gastric cancer
      patient. A 42-year-old female with stage III gastric cancer underwent radical
      gastrectomy and was given mitomycin-C at 10 mg/m2 intravenously every four weeks
      as adjuvant therapy. Hemolytic uremic syndrome was diagnosed three months after
      the last dose of mitomycin-C administration. The most prominent symptoms included
      pallor, hypertension and anasarca, with laboratory evidence of microangiopathic
      hemolytic anemia, azotemia and hyperkalemia. Her disease was progressive, but
      fortunately stabilized after staphylococcus column A dialysis. Her disease
      remained in remission for 24 months from the time of diagnosis, and then relapsed
      in the form of peritoneal carcinomatosis with partial intestinal obstruction.

PMID- 9152803
TI  - Management of early gastric cancer in Japan.

PMID- 9152804
TI  - Notes on cancer management from a visiting Australian researcher.

PMID- 9152805
TI  - Detection of interleukin-1 beta in the tear fluid of patients with corneal
      disease with or without conjunctival involvement.
AB  - To investigate the role of Interleukin-1 (IL-1) in the pathobiology of the
      cornea, we measured IL-1 beta concentration in tear fluid samples from patients
      with corneal disease. Twenty patients with unilateral corneal disease were
      included in the study. Tear fluid samples were collected during the active stages
      of the disease and following resolution. The fellow (unaffected) eyes served as
      controls. The concentration of IL-1 beta in the tear fluid samples was measured
      using a sandwich ELISA method. IL-1 beta was detected in tear fluid from five
      eyes (three eyes with chemical burns, one with a Pseudomonas aeruginosa corneal
      ulcer, and one with a peripheral corneal ulcer) at concentrations between 29 and
      218 pg/mL. IL-1 beta was not detected in tear fluid from the remaining 15
      affected eyes, nor from the control eyes. The detection of IL-1 beta in tear
      fluid correlated with limbal conjunctival involvement, but did not correlate with
      the type of disease, size of epithelial defect, or degree of stromal involvement.
      IL-1 beta in the tear fluid may be one of the factors modifying the complex
      inflammatory process of the anterior ocular surface.

PMID- 9152806
TI  - Flow cytometry tear analysis in patients with chronic allergic conjunctivitis.
AB  - Tears from patients with chronic allergic conjunctivitis were analyzed with flow
      cytometry to determine the function of the T lymphocyte-related immunological
      reactions in the disease pathogenesis. Twenty-eight patients and 22 normal
      volunteers were studied; tears were obtained with capillary tubes. T helper/T
      suppressor ratios and the percentages of HLA DR+, CD23+, and CD3+ cells were
      significantly higher in patients than in controls. This study provides support
      for the hypothesis that chronic allergic conjunctivitis results from T lymphocyte
      related immunological reactions.

PMID- 9152807
TI  - Type VI collagen bound to collagen fibrils by chondroitin/dermatan sulfate
      glycosaminoglycan in mouse corneal stroma.
AB  - We investigated the ultrastructural localization of type VI collagen in mouse
      corneal stroma and its relationship to striated collagen fibrils and
      glycosaminoglycans, using chondroitinase ABC digestion and immunoelectron
      microscopy with colloidal gold particles. After chondroitinase ABC digestion, the
      arrangement of striated collagen fibrils was disrupted, and large spaces
      containing widely scattered fibrils appeared. The spaces were filled by
      filamentous networks that were stained by anti-type VI collagen IgG, which were
      apparently clumps of beaded filament. Interfibrillar type VI collagen beaded
      filaments and immunogold particles decreased. Our results indicate that type VI
      collagen is bound to the striated collagen fibrils by mediation of
      chrondroitin/dermatan sulfate glycosaminoglycan or proteoglycan. We believe that
      this interaction is essential to the orderly arrangement of the striated collagen
      fibrils, which results in corneal transparency.

PMID- 9152808
TI  - Histology of anterior capsule edges produced by CCC and DC.
AB  - We compared the postoperative characteristics of the anterior capsule edges
      produced by two incision techniques: continuous curvilinear capsulorhexis (CCC)
      and diathermy capsulorhexis (DC). We examined the incised rims of human and
      animal capsules histologically and also compared the configuration and strength
      of the rims produced in animal experimentation. Histological examination of
      rabbit lenses revealed that 0.5 seconds was sufficient for coagulation of the
      anterior capsule: longer times caused deeper cortical tissue damage.
      Experimentally produced small capsulorhexis (3.5 mm diameter) with DC produced
      edges were less elastic than with CCC when tension was applied.

PMID- 9152810
TI  - Apoptosis in retinal ganglion cell decrease in human glaucomatous eyes.
AB  - Hematoxylin-eosin staining, the TUNEL method for in situ detection of the
      intranuclear DNA fragmentation, which indicates apoptosis, and electron
      microscopy were used to study the morphologic changes in specimens from the eyes
      of 8 patients with secondary glaucoma and 2 normal control eyes to evaluate our
      hypothesis that apoptosis causes a decrease in retinal ganglion cells in human
      glaucomatous eyes. The TUNEL method permits identification of intranuclear DNA
      fragmentation. Apoptosis was found in the ganglion cells of 2 glaucomatous eyes
      with recent sight loss, and in the ganglion cells of a control eye from a 95-year
      old subject, taken at autopsy. Results of our study indicate that a decrease in
      retinal ganglion cells in glaucomatous eyes is caused by apoptosis. In addition,
      apoptosis resulting from aging must be considered in order to understand the
      reduction of retinal ganglion cells in the glaucomatous eyes of elderly patients.

PMID- 9152809
TI  - Hexagonal structures at lens capsule zonular attachments.
AB  - Two years after uneventful phacoemulsification with posterior intraocular lens
      implant in an 84-year-old female patient, the capsular bag and enclosed
      intraocular lens luxated into the vitreous cavity. A vitrectomy was done to
      extract the lens and capsule for electron-microscopic examination. We found very
      few zonular attachments to the capsule, but did note hexagonal structures of
      unknown significance that our study indicates may be related to the lens
      epithelium.

PMID- 9152811
TI  - Preoperative factors influencing effectiveness of surgery in adult strabismus.
AB  - To identify preoperative factors which influence the effectiveness of strabismus
      surgery in adults, we retrospectively reviewed the records of 179 patients > 15
      years old (131 with exotropia, 48 with esotropia) who had had combined recession
      and resection surgery for correction of horizontal strabismus. Eighteen
      preoperative variables were evaluated; those with significant influence on the
      surgical outcome, measured by the degree of change in deviation per millimeter of
      surgery, were identified by stepwise regression analysis. In patients with
      exotropia, preoperative distance deviation and average spherical equivalent were
      significant predictors of outcome at both 1 month (multiple R, 0.37) and 6 months
      (0.63) after surgery. In esotropic patients, significant variables at 1 month
      (multiple R, 0.57) and 6 months (0.77) were preoperative distance deviation and
      dissociated vertical deviation (DVD). Preoperative distance deviation is the
      common significant influence on surgical effectiveness for horizontal strabismus
      in adults, for both exotropia and esotropia. Additional significant predictors
      are average spherical equivalents in exotropic patients, and DVD in esotropic
      patients.

PMID- 9152812
TI  - Uveitis-glaucoma-hyphema syndrome after posterior chamber intraocular lens
      implantation.
AB  - This article describes uveitis-glaucoma-hyphema (UGH) syndrome following
      posterior chamber intraocular lens (PCIOL) implantation in a 51-year-old male
      patient who had had intermittent blurred vision for 2 years prior to cataract
      surgery. We found the lens haptics fixed in the sulcus and the lens rotated. The
      lens was extracted and a new implant inserted with a transscleral suture.
      Etiology of the syndrome in this patient was an unstable sulcus fixation.

PMID- 9152813
TI  - Marked decrease in intraocular pressure in a neovascular glaucoma patient during
      hemodialysis.
AB  - While the relationship between intraocular pressure and plasma osmolarity has
      been investigated during hemodialysis, no research has been published concerning
      the relationship between intraocular pressure and plasma colloid osmotic pressure
      during hemodialysis. We describe a patient with neovascular glaucoma who
      demonstrated a marked decrease in intraocular pressure during hemodialysis. The
      patient's intraocular pressure, plasma osmolarity, plasma colloid osmotic
      pressure, and body weight were evaluated every 30 minutes during hemodialysis
      lasting 4.5 hours. Plasma osmolarity was almost constant during hemodialysis
      (beginning: 295 mOsm/L; ending: 305 mOsm/L), and plasma colloid osmotic pressure
      increased (beginning: 23.0 mm Hg; peak: 27.2 mm Hg). Weight loss was 5.7 kg.
      Intraocular pressure decreased markedly during hemodialysis (beginning: 53 mm Hg;
      ending: 14 mm Hg). This sharp decrease in intraocular pressure and the increase
      in plasma colloid osmotic pressure, indicate a relationship between plasma
      colloid osmotic pressure and the change in intraocular pressure during
      hemodialysis.

PMID- 9152814
TI  - Superior orbital fissure syndrome caused by intraorbital spread of a cutaneous
      squamous cell carcinoma and not detected on computed tomography and magnetic
      resonance imaging.
AB  - Intraneural and perineural spread of a squamous cell carcinoma of the frontal
      region via the orbit to the cranial cavity is a rare cause of a superior orbital
      fissure syndrome. This mode of tumor spread, for which a previously excised
      invasive malignant tumor is responsible, is rarely reported. The absence of an
      intraorbital mass and the fact that computed tomography (CT) and magnetic
      resonance imaging (MRI) are normal make the diagnosis extremely difficult. We
      describe a 76-year-old patient in whom both intraneural and perineural tumor
      growth deep into the orbit caused acute oculer motility disturbances, visual
      impairment, and ocular dysfunction with subsequent cerebral and vascular
      dysfunction. Surgery, radiotherapy, and orbital exenteration did not prevent
      spread of the tumor toward vital intracranial and intracerebral structures. Even
      the advanced diagnostic modalities of CT and MRI failed to reveal the cause of
      the pathologic process in our patient. In such a case, one should look carefully
      for both intraneural and perineural tumor invasion on previous histologic
      material and, if positive, treat the patient with radical surgery on purely
      clinical grounds as early as possible.

PMID- 9152815
TI  - The Kobe earthquake and recurrent endogenous uveitis.
AB  - The mechanism of recurrent endogenous uveitis remains uncertain but it is
      generally believed to be affected by both heredity and environment. On January
      17, 1995, the Hanshin-Awaji (Kobe) area of Japan experienced a major earthquake
      which killed more than 6300 people and forced 310,000 to take refuge in emergency
      shelters. All inhabitants of this area suffered severe stress due to the sudden
      changes in their living environment. We investigated the recurrence rate of
      endogenous uveitis before and after the earthquake in 116 patients who had been
      followed for more than 2 years (since July 17, 1993) at Kobe University Hospital.
      The postquake rate was significantly higher than the prequake rate (10% vs 3%);
      women were more often affected than men. Our data suggests that psychological
      stress due to the sudden changes in living conditions following the earthquake
      may have triggered the recurrences. It might be important to provide
      psychological as well as physical care for these patients after a disaster.

PMID- 9152816
TI  - Clinical studies of ocular motility disturbances: Part 2. Risk factors for
      ischemic ocular motor nerve palsy [corrected].
AB  - A case-control study of 46 Japanese patients who were diagnosed by exclusion as
      having ischemic ocular motor nerve palsy and who exhibited spontaneous recovery
      within 4 months was done to evaluate the risk factors involved. We also evaluated
      the association between the number of risk factors and the spontaneous recovery
      or recurrence periods. Ischemic ocular motor nerve palsy is closely related to
      diabetes mellitus and coronary artery disease. Patients tended to be obese; many
      had two or more risk factors. Aging, in combination with two or more risk
      factors, seems to increase the likelihood of developing this disease. Diabetes
      mellitus is a particularly significant risk factor for this type of palsy,
      especially in combination with hypertension.

PMID- 9152817
TI  - A microbiologist's guide to travellers abroad: do as I say not as I do.
AB  - Clinical microbiologists do not normally prescribe prophylactic antibiotics for
      travellers' diarrhoea, and when questioned at a Hospital Infection Society (HIS)
      meeting only 2% admitted doing so. During a HIS visit to India, 5 (28%) members
      took daily ciprofloxacin prophylaxis and none of them developed diarrhoea.

PMID- 9152818
TI  - The bacteriological quality of hospital-prepared infant feeds.
AB  - Twenty-four pasteurized infant feeds, prepared in a Glasgow hospital, were
      examined microbiologically. All produced a satisfactory total aerobic mesophilic
      count of < or = 1.0 x 10(4) cfu/g (mean 6.3 x 10(1) cfu/g) within 1 h of
      preparation. Bacillus cereus was detected in two infant feeds immediately after
      preparation and one of these had a B. cereus count of 1.4 x 10(3) cfu/g exceeding
      the recommended safety limit of < or = 1.0 x 10(3) cfu/g. Subsequent storage over
      a 14 h period at 25 degrees C or greater resulted in the appearance of B. cereus
      in a further eight feeds, the majority of which exceeded the safety limit of
      10(3) cfu/g. The microbiological quality of each infant feed depended on the type
      and number of organisms initially present, and on the temperature and duration of
      storage. Incubation of feeds at < or = 10 degrees C for 14 h did not alter the
      microbiological quality (P = 0.05). While Bacillus licheniformis and Bacillus
      subtilis were the predominant organisms isolated within 8 h of incubation (45.8
      and 20.8% of feeds, respectively), additional storage resulted in the emergence
      of B.cereus I (25%) and II (20.8%) as dominant Bacillus spp. The addition of
      glucose polymers and other supplements to infant formulae did not affect the type
      and number of organisms present (P = 0.05). Diarrhoeal enterotoxin was detected
      in three of the five formulations which supported the growth of B. cereus II via
      the B. cereus enterotoxin reverse phase latex agglutination test BCET-RPLA
      system. Although the infant feeds were of similar microbiological quality (P =
      0.05), the majority of Bacillus spp. isolated have been previously implicated in
      either foodborne illnesses and/or opportunist infections.

PMID- 9152819
TI  - Usefulness of intrinsic surgical wound infection risk indices as predictors of
      postoperative pneumonia risk.
AB  - The main objective of this report was to use two indices of intrinsic surgical
      wound infection risk, the SENIC index (Haley et al., 1985) and the NNIS index
      (Culver et al., 1991), to predict risk of postoperative pneumonia in general
      surgery patients. A prospective cohort study on 1483 patients admitted under the
      general surgery speciality of a tertiary hospital was performed. The main outcome
      measure was postoperative pneumonia. Relative risk and their 95% confidence
      intervals (CIs) were estimated. Stepwise logistic regression analysis was used to
      select the main determinant predictors. During follow-up, 19 (1.3%) patients
      acquired postoperative pneumonia. Common risk factors of postoperative pneumonia
      were identified: mechanical ventilation, age, upper abdominal surgery, severity
      of illness, obesity, hypoalbuminaemia, and use of histamine type 2 receptor
      antagonists. Both the SENIC and the NNIS indices showed a statistically
      significant association (P < 0.001) with postoperative pneumonia risk: the higher
      the score the greater the risk. Stepwise logistic regression analysis selected
      five variables: (1) mechanical ventilation [odds ratio (OR) = 9.8, 95% CI 2.7
      35.6]; (2) upper abdominal surgery (OR = 4.7, 95% CI 1.6-13.9); (3) chronic lung
      disease (OR = 5.9, 95% CI 1.7-21.2); (4) the NNIS index (OR for each point = 2.2,
      95% CI 1.1-4.4); and (5) obesity, measured by a body mass index greater than the
      90th percentile (OR = 2.9, 95% CI 0.9-9.4). In conclusion, both the SENIC and the
      NNIS indices were related to postoperative pneumonia risk. The NNIS index may be
      a better predictor.

PMID- 9152820
TI  - Hospital-acquired infections among surgical patients in a Brazilian hospital.
AB  - A historical cohort study was conducted among surgical patients in a large
      general hospital in Porto Alegre, Brazil between March 1992 and May 1993. Data
      were collected by means of a retrospective chart review, which followed a
      standardized method based on the systematic review of all clinical and laboratory
      information available in the hospital records. The criteria for diagnosis of all
      hospital-acquired infections (HAIs) were based on those from the Centers for
      Disease Control, Atlanta. In total, 890 HAIs were detected among the 4199
      patients included in the cohort. The incidence rate of HAIs for all sites
      combined was 21.20%. Incidence rates ranged from 2.95% for bloodstream infections
      to 8.65% for surgical wound infections. The overall incidence density was 16.32
      HAIs per 1000 patient-days. Incidence densities ranged from 2.03 for bloodstream
      infections to 7.46 per 1000 patient-days for surgical wound infections. The
      median incubation period for surgical wound infections was seven days, and 29.4%
      of these infections were detected at post-discharge. Gram-negative bacteria were
      the most common organisms implicated in HAIs.

PMID- 9152821
TI  - The use of povidone iodine in exit site care for patients undergoing continuous
      peritoneal dialysis (CAPD).
AB  - Exit site infection is a major risk factor for the development of peritonitis in
      continuous ambulatory peritoneal dialysis. The frequency of infection can be
      reduced by scrupulous exit site care with or without topical antiseptics. A
      randomized trial was performed of 149 catheters in 130 patients to assess any
      additional benefits conferred by the use of povidine iodine dry powder spray at
      dressing changes over an existing strict protocol of exit care. Exit infections
      occurred in 14 (18%) of 77 patients using spray and in 15 (21%) of 72 patients
      not using spray. The risk of peritonitis was also similar in each group. The
      proportion of infections caused by Staphylococcus aureus was reduced in the spray
      group, but those caused by Pseudomonas aeruginosa were increased. Rash occurred
      in 6% of those using the spray. The use of the spray did not therefore seem
      justified.

PMID- 9152822
TI  - Risk factors for oxacillin/methicillin resistance in coagulase-negative
      staphylococci.
AB  - The clinical variables associated with isolation of oxacillin- and methicillin
      resistant, coagulase-negative staphylococci (CNS) from blood cultures of
      hospitalized patients were studied. One hundred CNS strains (49 oxacillin
      susceptible; 51 oxacillin-resistant) isolated consecutively from one of two or
      more sets of blood cultures were collected. Only two variables were independently
      associated with recovery of oxacillin/methicillin-resistant strains by a
      multivariate analysis: length of hospital stay > 10 days (OR 5.2, 95% CI = 1.7
      15.7), and administration of antimicrobial agents in the previous 14 days (OR
      4.5, 95% CI = 1.7-11.7). Analysis of the antibiotics administered indicated that
      only beta-lactams were associated with a statistically significant risk of
      resistance to oxacillin/methicillin (OR of beta-lactams vs no antibiotics = 6.94,
      95% CI = 1.9-25.3; OR of non-beta-lactams vs no antibiotics = 2.64, 95% CI = 0.8
      8.3). Length of hospital stay (especially > 10 days) and prior administration of
      antimicrobial agents (mainly beta-lactams) independently predicted the presence
      of oxacillin/methicillin-resistant CNS in blood cultures.

PMID- 9152823
TI  - Anonymous questionnaire survey on the knowledge and practices of hospital staff
      in infection control.
AB  - We carried out an anonymous questionnaire survey to assess the extent to which
      hospital medical and nursing staff were familiar with the written policies and
      procedures of infection control and their intended course of action in situations
      where no formal policies were available. All 25 full-time medical staff below the
      grade of consultant and 70 of 163 permanent nursing staff caring for inpatients
      at one day shift were sampled. Nineteen (76%) medical and 56 (80%) nursing staff
      returned their copies. Nurses were significantly more familiar with all written
      policies and procedures than medical staff. They were also more likely to seek
      advice in situations where there were no written guidelines. Many hospital staff
      were uncertain about the practical details of policies and procedures for
      infection control. Ways to educate and motivate staff to comply with infection
      control measures are urgently required; some degree of national standardization
      of policies and procedures in infection control is desirable.

PMID- 9152824
TI  - Staff carriage of methicillin-resistant Staphylococcus aureus (EMRSA 15) and the
      home environment: a case report.
AB  - A case of refractory carriage of methicillin-resistant Staphylococcus aureus
      (MRSA) by a nurse is described. The nurse's home environment was widely
      contaminated with MRSA and two family members acquired the organism. Relapse of
      carriage after routine anti-staphylococcal measures and three negative sets of
      screening specimens resulted in a hospital outbreak involving three patients. The
      problem was finally terminated after a co-ordinated commercial cleaning of the
      house, thermal disinfection of all linen and replacement of some soft
      furnishings.

PMID- 9152825
TI  - Dispose of disposables?
AB  - We investigated the implications of a change from disposable to regular crockery
      and cutlery, and the installation of a dishwasher on a 12-bedded-infectious
      diseases ward. A limited microbiological study of used disposable cutlery
      revealed contamination by methicillin-resistant Staphylococcus aureus of one
      utensil out of 12. Changing to conventional utensils could be recommended if a
      dishwasher meeting DHSS requirements was installed and safe working practices
      introduced.

PMID- 9152826
TI  - Killing activity of microwaves in milk.

PMID- 9152827
TI  - Eradication of throat carriage of methicillin-resistant Staphylococcus aureus.

PMID- 9152828
TI  - Long-term in-vitro survival of an epidemic MRSA phage-group III-29 strain.

PMID- 9152829
TI  - Possible prolonged environmental survival of small round structured viruses.

PMID- 9152830
TI  - Epigenetic modification and uniparental inheritance of H19 in Beckwith-Wiedemann
      syndrome.
AB  - Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome associated
      with a characteristic pattern of visceromegaly and predisposition to childhood
      tumours. BWS is a genetically heterogeneous disorder; most cases are sporadic but
      approximately 15% are familial and a small number of BWS patients have
      cytogenetic abnormalities involving chromosome 11p15. Genomic imprinting effects
      have been implicated in familial and non-familial BWS. We have investigated the
      molecular pathology of 106 sporadic BWS cases; 17% (14/83) of informative cases
      had uniparental disomy (UPD) for chromosome 11p15.5. In each case UPD appeared to
      result from a postzygotic event resulting in mosaicism for segmental paternal
      isodisomy. The critical region for isodisomy was refined to a 25 cM interval
      between D11S861 and D11S2071 which contained the IGF2, H19, and p57(KIP2) genes.
      In three cases isodisomy for 11q markers was detected but this did not extend
      further than 11q13-q21 suggesting that complete chromosome 11 disomy may not
      produce a BWS phenotype. The allele specific methylation status of the H19 gene
      was investigated in 80 sporadic BWS cases. All 13 cases with UPD tested displayed
      hypermethylation consistent with an excess of paternal H19 alleles. In addition,
      five of 63 (8%) cases with normal biparental inheritance had H19 hypermethylation
      consistent with an "imprinting centre" mutation (ICM) or "imprinting error" (IE)
      lesion. The phenotype of patients with putative ICM/IE mutations was variable and
      overlapped with that of non-UPD sporadic BWS cases with normal H19 methylation.
      However, exomphalos was significantly (p < 0.05) more common in the latter group.
      These findings may indicate differential effects on the expression of imprinted
      genes in chromosome 11p15 according to the precise molecular pathology. Analysis
      of H19 methylation is useful for the diagnosis of both UPD or altered imprinting
      in BWS and shows that a variety of molecular mechanisms may cause relaxation of
      IGF2 imprinting in BWS.

PMID- 9152831
TI  - The genetics of primary nocturnal enuresis: inheritance and suggestion of a
      second major gene on chromosome 12q.
AB  - Primary nocturnal enuresis (PNE), or bedwetting at night, affects approximately
      10% of 6 year old children. Genetic components contribute to the pathogenesis and
      recently one locus was assigned to chromosome 13q. We evaluated the genetic
      factors and the pattern of inheritance for PNE in 392 families. Dominant
      transmission was observed in 43% and an apparent recessive mode of inheritance
      was observed in 9% of the families. Among the 392 probands the ratio of males to
      females was 3:1 indicating sex linked or sex influenced factors. Linkage to
      candidate regions was tested in 16 larger families segregating for autosomal
      dominant PNE. A gene for PNE was excluded from chromosome 13q in 11 families,
      whereas linkage to the interval D13S263-D13S291 was suggested (Zmax = 2.1) in
      three families. Further linkage analyses excluded about 1/3 of the genome at a 10
      cM resolution except the region around D12S80 on chromosome 12q that showed a
      positive two point lod score in six of the families (Zmax = 4.2). This locus
      remains suggestive because the material was not sufficiently large to give
      evidence for heterogeneity. Our pedigree analysis indicates that major genes are
      involved in a large proportion of PNE families and the linkage results suggest
      that such a gene is located on chromosome 12q.

PMID- 9152832
TI  - Further delineation of Nevo syndrome.
AB  - Nevo syndrome is an autosomal recessive syndrome characterised by prenatal
      overgrowth, joint laxity, kyphosis, wrist drop, spindle shaped fingers, and volar
      oedema. Four children from two families have been reported previously. We report
      two further children from two unrelated Arab families from two different tribes.
      Both presented at birth with hypotonia, joint laxity, kyphosis, wrist drop,
      spindle shaped fingers, and volar oedema. Both have delayed motor development at
      the ages of 2 years 10 months and 3 months respectively. Cognitive development is
      normal in one, and the other case appears to be developing normally at 3 months
      of age. One has, in addition, a wide spinal canal on MRI of the spine indicating
      some degree of dural ectasia. This report brings the total number of children
      reported with this syndrome to six from four families; three of these families
      are Arab. This indicates that the gene for this syndrome is probably commoner in
      Arabs than in other populations.

PMID- 9152833
TI  - Analysis of the 5' upstream sequence of the Huntington's disease (HD) gene shows
      six new rare alleles which are unrelated to the age at onset of HD.
AB  - The CAG repeat number in the Huntington's disease (HD) gene accounts for about
      50% of the variation seen in age at onset of HD. In order to determine whether
      promoter sequence variation can contribute to the residual variation in age at
      onset, we studied the conserved 303 bp region upstream of the +1 translation
      start site in the HD gene in a population of 56 control East Anglians, 30
      Africans, 34 Japanese, and 208 English Huntington's disease patients. A
      surprisingly high degree of variation was found. Seven alleles were identified,
      comprising four polymorphisms: two single base pair substitutions, a 6 bp VNTR
      present as one or two copies, and a 20 bp VNTR with one to three copies of the
      tandem repeat. No correlation between polymorphisms and age at onset of symptoms
      was found in HD patients. The 6 bp and 20 bp stretches are present only in single
      copies in the chimpanzees and gorilla, suggesting that these VNTRs have evolved
      by duplication of the core sequences in the human lineage.

PMID- 9152834
TI  - Genotypic diagnosis of familial Mediterranean fever (FMF) using new
      microsatellite markers: example of two extensive non-Ashkenazi Jewish pedigrees.
AB  - Familial Mediterranean fever is an autosomal recessive disease characterised by
      multiple attacks of serosal inflammation in the absence of treatment. In the
      absence of timely diagnosis, renal amyloidosis is a life threatening
      complication. The diagnosis is often missed because no specific test is
      available. Early colchicine treatment prevents attacks and renal complications.
      The FMF gene (MEF) has been mapped to chromosome 16p 13.3 but has not yet been
      identified. We compared the suitability of a series of microsatellite markers
      (four of them were new) and propose the routine use of seven of these markers,
      exhibiting alleles in strong linkage disequilibrium with the disease and
      informative in 100% of diagnosed patients. Moreover, the discovery of a
      homozygous status for the 3-3-9 (or 3-3-18) haplotype at the core loci (D16S3070,
      D16S3082, and D16S3275), which was found in 73% non-Ashkenazi Jewish patients,
      points to a diagnosis of FMF, even in sporadic cases, with a risk of error of
      only 2.10(-5). Two extensive pedigrees covering most indications for genetic
      counselling are presented, showing that it is now possible both prospectively and
      retrospectively to identify members likely to have MEF mutations. With the help
      of this accurate test, colchicine treatment can be better targeted, especially
      where the symptomatology is mild or atypical.

PMID- 9152835
TI  - Psychological distress in applicants for predictive DNA testing for autosomal
      dominant, heritable, late onset disorders. The Rotterdam/Leiden Genetics
      Workgroup.
AB  - In a comparative study on the effects of predictive DNA testing for late onset
      disorders, pre-test psychological distress was assessed in people at risk for
      Huntington's disease (HD, n = 41), cerebral haemorrhage (HCHWA-D, n = 9), breast
      and ovarian cancer (HBOC, n = 24), and polyposis coli (FAP, n = 45). Partners, if
      available, also participated in the study. Distress was measured with the
      subscales Intrusion and Avoidance of the Impact of Event Scale. People at risk
      for the neurodegenerative disorders reported more avoidance than those at risk
      for the cancer syndromes. People at risk for FAP and partners of those at risk
      for HBOC reported less intrusion than the others at risk and the other partners.
      Subjects who were more distressed reported more experiences with the disease in
      close relatives, the disease having a great impact on their lives, having
      considerations against predictive testing, expecting that being identified as a
      gene carrier would have adverse effects, and expecting relief after being
      identified as a non-carrier. Test candidates who expected an increase of personal
      problems showed higher avoidance, whereas those who could better anticipate
      future life as a carrier had higher intrusion levels. Generally, subjects with
      high distress levels are of more concern to the healthcare professional than
      those with low distress levels. However, high distress may reflect worrying as a
      mental preparation for the test result, whereas low distress may indicate denial
      avoidance behaviour and poor anticipation of the test outcome. In pre-test
      counselling sessions, this should be acknowledged and addressed.

PMID- 9152836
TI  - Homozygosity by descent for a rare mutation in the myophosphorylase gene is
      associated with variable phenotypes in a Druze family with McArdle disease.
AB  - We examined a large consanguineous Druze family with McArdle disease for
      mutations in the glycogen myophosphorylase (PYGM) gene. All affected subjects
      were autozygous for a single G to A transition that abolishes the 5' consensus
      splice site in the first nucleotide of intron 14. The G to A transition is a rare
      mutation, with only one previous report in a single white subject heterozygous
      for this mutation and another, more common, mutation at codon 49. The kindred in
      our study is the first family reported in which disease is caused by homozygosity
      for this rare mutation. This kindred was originally reported as the first
      familial case of McArdle disease in the Druze.

PMID- 9152839
TI  - Meiotic instability associated with the CAGR1 trinucleotide repeat at 13q13.
AB  - CAGR1 is a recently characterised polymorphic trinucleotide repeat localised to
      13q13, which has been suggested as a possible candidate gene for neurological
      disorders that manifest genetic anticipation. To provide evidence in support of
      this hypothesis, a large number of chromosomes (n = 928) from patients with a
      wide variety of neurological diseases were screened for evidence of repeat
      expansion and meiotic instability. One person with a CAGR1 repeat number of 50
      was identified (normal range 9-29). Subsequent molecular analyses of CAGR1 repeat
      number in additional family members showed meiotic instability of a (CAG)45
      allele through three generations. While CAGR1 repeat number did not correlate
      with a readily discernible phenotype in this family, the finding of meiotic
      stability and mendelian inheritance of normal CAG alleles and meiotic instability
      of larger repeats fulfil several criteria thought essential for pathologically
      relevant mutations of this type. Thus, these data strengthen the hypothesis for a
      role of CAGR1 in the development of an as yet molecularly uncharacterised human
      neurological disease.

PMID- 9152837
TI  - Trisomy 15 rescue with jumping translocation of distal 15q in Prader-Willi
      syndrome.
AB  - We report a patient with Prader-Willi syndrome (PWS) and mosaicism for a de novo
      jumping translocation of distal chromosome 15q, resulting in partial trisomy for
      15q24-qter. A maternal uniparental heterodisomy for chromosome 15 was present in
      all cells, defining the molecular basis for the PWS in this patient. The
      translocated distal 15q fragment was of paternal origin and was present as a
      jumping translocation, involving three different translocation partners,
      chromosomes 14q, 4q, and 16p. The recipient chromosomes appeared cytogenetically
      intact and interstitial telomere DNA sequences were present at the breakpoint
      junctions. This strongly suggests that the initial event leading to the
      translocation of distal 15q was a non-reciprocal translocation, with fusion
      between the 15q24 break-point and the telomeres of the recipient chromosomes.
      These observations are best explained by a partial zygotic trisomy rescue and
      comprise a previously undescribed mechanism leading to partial trisomy.

PMID- 9152838
TI  - Ehlers-Danlos syndrome has varied molecular mechanisms.

PMID- 9152840
TI  - Chromosome 18q22.2-->qter deletion and a congenital anomaly syndrome with
      multiple vertebral segmentation defects.
AB  - Multiple vertebral segmentation defects occur in a group of conditions variably
      associated with anomalies of other organ systems. This report describes a female
      child in whom a deletion of chromosome 18 (18q22.2-->qter) is associated with
      congenital anomalies including multiple vertebral segmentation defects resembling
      sporadic spondylocostal dysplasia. The child also has unilateral renal agenesis
      and unilateral fibular aplasia. The association of severe multiple vertebral
      segmentation defects with 18q- in this patient suggests the possibility that a
      gene important for somite formation or vertebral differentiation maps to this
      segment of chromosome 18.

PMID- 9152841
TI  - Autosomal dominant inheritance of Weaver syndrome.
AB  - Most report of Weaver syndrome have been sporadic cases and the genetic basis of
      the syndrome is uncertain. This report of an affected father and daughter
      provides evidence for autosomal dominant inheritance.

PMID- 9152842
TI  - A novel mutation (a886g) in exon 5 of FGFR2 in members of a family with Crouzon
      phenotype and plagiocephaly.
AB  - We identified a novel mutation in members of a family with signs of Crouzon
      syndrome and plagiocephaly. In affected members of the family an A-->G transition
      was found at position 886 in exon 5 of the fibroblast growth factor receptor 2
      (FGFR2) gene. The base change results in the replacement of a lysine by glutamic
      acid in Ig-like loop III of FGFR2. The unusual finding of plagiocephaly in these
      Crouzon patients may either be the result of the type of mutation or because of
      genetic and environmental factors that affect the phenotype in addition to the
      mutated FGF receptor.

PMID- 9152843
TI  - Chromosome 22q11 deletion presenting as the Potter sequence.
AB  - A female fetus with the Potter sequence, caused by unilateral renal agenesis and
      contralateral multicystic renal dysplasia, was found to have a submicroscopic
      deletion in chromosome 22q11. The only associated anomaly was agenesis of the
      uterus and oviducts (Von Mayer-Rokitansky-Kuster anomaly). The deletion was
      inherited from the father, who presented the typical velocardiofacial syndrome
      phenotype, but no urological anomalies. This observation further extends the
      clinical spectrum associated with a deletion in 22q11.

PMID- 9152844
TI  - Clinical features in four patients with Angelman syndrome resulting from paternal
      uniparental disomy.
AB  - Angelman syndrome (AS) is a complex neurological disorder with different genetic
      aetiologies. It is not known whether the clinical features vary depending on the
      genetic mechanism. We report four patients with AS owing to uniparental disomy
      (UPD). There were two males and two females, with a mean age of 8 years (range 7
      to 11 years). All patients had a happy disposition, hyperactive behaviour, and
      the characteristic facial phenotype of AS, but in three there was a normal head
      circumference, two had epilepsy, ataxic movements were mild in three, the mean
      age of onset of walking was 2.4 years, and there was some sign language in all
      four patients. Our cases add further weight to the previously reported
      impressions of a milder phenotype in cases of AS resulting from UPD than in
      deleted AS patients. Patients suspected of having AS, but who are considered
      atypical, warrant DNA testing.

PMID- 9152845
TI  - Interstitial deletion of band 3q25.
AB  - Interstitial deletions of the long arm of chromosome 3 are rare. We report a man
      with an interstitial deletion involving band 3q25. To our knowledge, this is the
      first patient to be described with this cytogenetic abnormality.

PMID- 9152846
TI  - Wiedemann-Rautenstrauch neonatal progeroid syndrome: report of three new
      patients.
AB  - Wiedemann-Rautenstrauch (WR) syndrome is known as a neonatal progeroid syndrome,
      with only few published case reports. We describe three additional patients, two
      of them sibs, showing the clinical features of WR syndrome. Skeletal
      abnormalities are reported and assays of hormones and lipids are presented in one
      patient. Disturbance in bone maturation and lipid and hormone metabolism appear
      to be involved in this neonatal progeroid syndrome.

PMID- 9152847
TI  - Angiotensin II induces apoptosis of adult ventricular myocytes in vitro.
AB  - To determine whether angiotensin II (Ang II) activates the suicide program of
      myocytes, primary cultures of adult rat ventricular myocytes were exposed to 10(
      9) M of Ang II, for 24 h. Ang II resulted in a five-fold increase in programmed
      myocyte cell death (PMCD) documented by the terminal deoxynucleotidyl transferase
      assay and confirmed by DNA agarose gel electrophoresis. Ang II stimulation was
      associated with translocation of the epsilon and delta isoforms of protein kinase
      C (PKC) which was coupled with an increase in cytosolic Ca2+ in the cells. The
      PKC inhibitor chelerythrine abolished Ang II-mediated increases in cytosolic Ca2+
      and PMCD. Similarly, pretreatment of cells with the intracellular Ca2+ chelator
      BAPTA/AM inhibited the formation of DNA strand breaks. Conversely, the Ca2+
      ionophore A23187 markedly increased PMCD. Finally, the AT1 receptor antagonist,
      losartan, completely blocked Ang II-induced PMCD, whereas the AT2 receptor
      antagonist, PD123319, did not attenuate this phenomenon. In conclusion, ligand
      binding of AT1 receptors on myocytes triggers PMCD by a mechanism involving PKC
      mediated increases in cytosolic calcium, which result in internucleosomal DNA
      fragmentation.

PMID- 9152848
TI  - Role of oxidative metabolism on endothelium-dependent vascular relaxation of
      isolated vessels.
AB  - The obligatory role of endothelium in mediating vasodilator response to numerous
      humoral agents has been definitely accepted. However, the chemical identity of
      endothelium-derived relaxing factor(s) (EDRF) and the mechanisms underlying its
      synthesis and release remain unclear. Much evidence suggests a
      compartmentalization of ATP into cells, such that ATP derived from glycolysis or
      from oxidative metabolism is used for different cellular functions. To
      investigate which energy source (i.e. oxidative v glycolytic metabolism) is
      preferentially used for the biosynthesis and/or release of EDRF, rings of rabbit
      thoracic aorta were studied in organ chambers. After preconstriction with PGF2
      alpha, inhibition of glycolysis with either iodoacetate (300 microM) (n = 6) or 2
      deoxyglucose (20 mM) (n = 6) did not affect concentration-response curve to the
      endothelium-dependent agent acetylcholine. In contrast, inhibition of oxidative
      metabolism with either 1 mM amytal or 5 microM rotenone markedly impaired
      relaxation to acetylcholine. In fact, maximal relaxation was 75 +/- 5% in control
      rings (n = 6), and 42 +/- 7% (P < 0.01) in amytal-treated rings (n = 6), whereas
      rotenone converted acetylcholine relaxation into constriction (n = 6; P < 0.001).
      The effect of amytal on endothelium-dependent relaxation was reversible,
      suggesting that endothelial cells were not damaged by the inhibitor. Amytal also
      markedly reduced endothelium-mediated relaxation to ADP (37 +/- 6%; P < 0.05; n =
      5), as well as to the calcium ionophore A23187. Neither mitochondrial inhibitor
      affected relaxation to nitroglycerin, an endothelium-independent agent. Finally,
      amytal did not affect relaxation to S-nitrosocysteine (a recently proposed EDRF)
      (n = 5), suggesting that the effects on acetylcholine and ADP responses were not
      due to non-specific interferences with EDRF once released from endothelial cells.
      In conclusion, our data demonstrate that the active process of biosynthesis
      and/or release of EDRF requires energy derived mainly from mitochondrial
      oxidative metabolism.

PMID- 9152849
TI  - FMLP actions and its binding sites in isolated human coronary arteries.
AB  - The chemoattractant f-Met-Leu-Phe (FMLP) can modulate human coronary arterial
      tone without the involvement of peripheral leukocytes. We investigated the
      actions of FMLP and its cellular mechanism in human coronary arteries isolated 2
      3 h after death. A single dose of FMLP (0.01-10 microM) produced transient
      contraction (or, followed by relaxation) responses in most human coronary rings
      examined. These responses to FMLP were in large part mediated by the generation
      of cyclooxygenase products, mainly thromboxane A2 (TXA2) and prostaglandin I2
      (PGI2). Radiolabeled N-formyl hexapeptide. 125I-f-Nle-Leu-Phe-Nle-Tyr-Lys bound
      densely to intimal and adventitial sites that accumulated macrophages (CD68
      positive) with a Kd of 14-29 nM and, further, weakly to the media with a Kd of
      2.4-3.6 microM. Several cell types including macrophages, endothelial cells and
      smooth muscle cells were positively immunostained for both TXA2 synthase and PGI2
      synthase. However, there was no significant relation between the magnitude of the
      responses to FMLP and dense macrophage accumulation in the intimal plaques or the
      adventitia. A reverse transcription-polymerase chain reaction showed predominant
      expression of FMLP receptor homologues, FPRH1 and FPRH2 mRNA, in human coronary
      medial tissues relative to that in leukocytes. In conclusion. FMLP produced
      transient tension changes in human coronary arteries, mainly via the generation
      of TXA2 and PGI2. This effect of FMLP did not appear to be mediated by the
      activation of densely accumulated intimal and/or adventitial macrophages, but by
      the activation of unidentified medial tissue cells which might have functional
      FMLP receptor homologues.

PMID- 9152850
TI  - Variations in the relative mRNA levels of actins and myosin heavy chains do not
      produce corresponding differences in their proteins in the adult human heart.
AB  - This paper examines the quantitative relationship between the expression of
      myosin heavy chain (MHC) and actin at both the levels of their mRNAs and their
      proteins. Explanted human left ventricle tissues were obtained from non-diseased
      (ND) individuals and from dilated cardiomyopathy (DCM) patients with terminally
      failing hearts who underwent heart transplantation. We found: (1) there are
      substantial differences in the stoichiometry of sarcomeric MHC and actin
      transcripts in hearts of DCM patients as well as in ND individuals; (2) there are
      substantial differences between levels of total sarcomeric actin transcripts from
      different individual patients; (3) by and large variations in transcript levels
      between samples from the same heart are much less than between samples from
      different hearts; and (4) the ratio of MHC to sarcomeric actin proteins expressed
      by different ND and DCM hearts remains essentially constant. We conclude that the
      human ventricle can accommodate a substantial imbalance between sarcomeric MHC
      and actin mRNA levels while maintaining a constant ratio of their corresponding
      proteins.

PMID- 9152852
TI  - Multiple cycles of preconditioning cause loss of protection in open-chest
      rabbits.
AB  - Although single or multiple bursts of ischemic preconditioning have been shown to
      protect against myocardial necrosis, the frequency-dependency of the protection
      afforded by multiple stimuli has not yet been systematically studied in the
      anesthetized animal. The aim of the present study was to characterize the effect
      of increasing numbers of preconditioning stimuli (5 min ischemia plus 10 min
      reperfusion) in a collateral-deficient species in vivo. Rabbits were anesthetized
      and divided into groups (n = 5-7/group) which were subjected to 0, 1, 2, 4, 6 or
      8 cycles of preconditioning (each comprising 5 min of regional ischemia plus 10
      min reperfusion) followed by 45 min of regional ischemia and 2 h reperfusion. An
      additional group, serving as a control, was subjected to eight cycles of
      preconditioning without a subsequent 45 min of regional ischemia. Infarct size
      (I) and risk zones (R) were delineated with the aid of tetrazolium staining and
      fluorescent particles and the I/R ratio was expressed as a percentage. Mean
      infarct size in the control group which had no preconditioning was 59.8 +/- 4.0%.
      This was reduced to 22.2 +/- 2.9%, 19.5 +/- 4.1% and 23.3 +/- 3.4% by one, two
      and four cycles of preconditioning. However, when the number of preconditioning
      cycles was increased to six or eight protection declined with infarct sizes of
      41.8 +/- 6.9% (P < 0.05 v zero preconditioning control group) and 47.1 +/- 7.6%
      (N.S. v zero preconditioning control group). In the group subjected to eight
      cycles of preconditioning without subsequent ischemia, infarction was not
      detected. In conclusion, in the anesthetized rabbit, beyond 4 cycles, protection
      against infarction diminishes with increasing numbers of preconditioning cycles.

PMID- 9152851
TI  - Cholinergic short-term conditioning and activation of ATP-sensitive K+ current in
      cat atrial myocytes.
AB  - In atrial myocytes, an initial exposure to acetylcholine (ACh1) exerts a short
      term conditioning effect such that a second ACh exposure (ACh2) activates ATP
      sensitive K+ current (IK,ATP). The purpose of the present study was to determine
      the mechanism underlying the short-term conditioning induced by ACh that results
      in subsequent ACh-induced activation of IK.ATP. Cat atrial myocytes were studied
      using a nystatin-perforated patch whole cell recording method. Changes in L-type
      Ca2+ current (ICa,L) amplitude were used as an index of relative changes in
      cyclic AMP (cAMP). The results show that when atrial myocytes are treated with
      two consecutive exposures to 10 microM ACh separated by a recovery interval, ACh2
      activates a larger increase in potassium conductance (gK+) than ACh1. The
      additional ACh2-induced increase in gK+ is selectively blocked by 10 microM
      glibenclamide, identifying the current as IK,ATP. Moreover, ICa,L activated
      immediately after the withdrawal of ACh1 exhibited a transient increase in
      amplitude above control (+ 76%), consistent with rebound stimulation of cAMP. Rp
      cAMPs (50 microM), a selective antagonist of cAMP-dependent protein kinase A,
      blocked the rebound stimulation of ICa,L and abolished ACh2-induced activation of
      IK,ATP. Thapsigargin (5 microM), an inhibitor of Ca2+ ATPase in the sarcoplasmic
      reticulum (SR), abolished ACh2-induced activation of IK,ATP without decreasing
      rebound stimulation of ICa,L. Rebound stimulation of ICa,L and ACh2-induced
      activation of IK,ATP both varied as a function of ACh1 duration. We conclude that
      withdrawal of an initial ACh exposure elicits a rebound cAMP-mediated stimulation
      of SR Ca2+ uptake. This mechanism induces a short-term conditioning in atrial
      myocytes such that a subsequent ACh exposure activates IK,ATP. The present
      results demonstrate novel cholinergic signaling mechanisms in the regulation of
      IK,ATP.

PMID- 9152853
TI  - Purification and characterization of human sarcomeric mitochondrial creatine
      kinase.
AB  - In order to set the basis for detailed clinical investigations, mitochondrial
      creatine kinase (Mi-CK) was purified to homogeneity from human cardiac muscle.
      Biophysical characterization by SDS-PAGE, gel permeation chromatography and by
      electron microscopy of negatively stained single molecules demonstrated that,
      similar to other vertebrate Mi-CKs, human sarcomeric Mi-CK occurs in two
      different oligomeric forms, dimers and octamers, that are readily
      interconvertible. The apparent MTs of Mi-CK protomers, dimers and octamers were
      43,600 +/- 800, 79,700 +/- 800 and 371,000 +/- 3000, respectively. In addition,
      isoelectric focussing proved to be a suitable technique for routinely
      distinguishing Mi-CK from cytosolic MM-CK and gave pl values of 8.30 +/- 0.04 and
      7.44 +/- 0.04 for octameric and dimeric human sarcomeric Mi-CK. Circumstantial
      evidence suggests that both the highly symmetrical structure and the high pI
      value of Mi-CK octamers are crucial determinants for the physiological functions
      of this enzyme.

PMID- 9152854
TI  - Downregulation of polo-like kinase correlates with loss of proliferative ability
      of cardiac myocytes.
AB  - Cardiac myocytes rapidly increase the cell number during the fetal and early
      neonatal period, but they lose their proliferative ability soon after birth. To
      understand the mechanism of how cardiac myocytes exit from the cell cycle, we
      examined the role of a newly identified serine/threonine kinase, polo-like kinase
      (Plk), in the process of proliferation of cardiac myocytes. Northern blot
      analysis revealed that Plk gene was abundantly expressed in cardiac myocytes and
      non-myocytes of fetal and neonatal rats but not in cardiocytes of adult rats.
      Western blot analysis showed that Plk protein was also detected only in fetal and
      neonatal hearts. During the early stage of cardiac differentiation. Plk
      expression was well correlated with the proliferative ability of cardiocytes. Plk
      mRNA was most abundant in undifferentiated embryonic stem (ES) cells and the mRNA
      levels decreased along with cardiac differentiation in the developing ES cell
      system. Once serum was deprived from the culture media, expression levels of Plk
      were markedly decreased and DNA was not synthesized in both cardiac myocytes and
      non-myocytes of neonatal rats. Re-addition of serum stimulated Plk gene
      expression and DNA synthesis in non-myocytes but not in cardiomyocytes. All these
      results taken together with the critical role of Plk in DNA synthesis in many
      cell types suggest that downregulation of Plk is important for the permanent
      withdrawal of cardiomyocytes from the cell cycle.

PMID- 9152855
TI  - Regression of cardiac hypertrophy normalizes glucose metabolism and left
      ventricular function during reperfusion.
AB  - It is not yet known if the alterations in myocardial glucose metabolism and the
      exaggerated left ventricular dysfunction that occur during reperfusion in
      hypertrophied hearts are reversible. Thus, we studied isolated working hearts
      from aortic-banded (n = 29) and sham-operated control (n = 32) male Sprague
      Dawley rats with or without enalapril maleate treatment (25.6 +/- 0.8 mg/kg per
      day, p.o.) to determine the effect of regression of cardiac hypertrophy on
      myocardial glucose metabolism and post-ischemic heart function. Hearts were
      perfused with buffer containing 1.2 mM palmitate, 11 mM [5-3H]/[U-14C]-glucose,
      0.5 mM lactate and 100 microU/ml insulin. Glucose metabolism [rates of glycolysis
      (3H2O production) and rates of oxidation (14CO2 production) of exogenous glucose]
      and heart function (heart rate x peak systolic pressure) were measured during 30
      min pre-ischemic perfusion and 60 min of reperfusion following 20 min of global,
      no-flow ischemia. Hearts from untreated aortic-banded rats were hypertrophied,
      being 27.6 +/- 1.8% larger than hearts from untreated control rats. Enalapril
      treatment caused regression of cardiac hypertrophy that normalized heart weight
      in aortic-banded rats. Rates of glycolysis of exogenous glucose in hearts from
      untreated aortic-banded rats were accelerated compared to rates in hearts from
      untreated control rats during pre-ischemic perfusion (4391 +/- 97 v 2652 +/- 69
      nmol glucose/min per g dry wt, respectively, P < 0.05) and reperfusion (2402 +/-
      58 v 1597 +/- 88 nmol glucose/min per g dry wt. respectively, P < 0.05). In
      contrast, rates of glycolysis of exogenous glucose in hearts from enalapril
      treated aortic-banded rats were normalized before and after ischemia. Rates of
      glycolysis of exogenous glucose in hearts of control rats were not affected by
      enalapril treatment. Oxidation of exogenous glucose was not different among
      groups either before or after ischemia. Function of hearts from untreated aortic
      banded rats at the end of reperfusion was significantly less than that of hearts
      from untreated control rats (23.9 +/- 2.6 v 32.2 +/- 0.7 mmHg x beats per
      min/1000, respectively, P < 0.05). As with myocardial glucose metabolism function
      of hearts from aortic-banded rats treated with enalapril was normalized during
      reperfusion. Thus, pharmacologically induced regression of pressure-overload
      cardiac hypertrophy normalizes glucose metabolism as well as left ventricular
      function during reperfusion.

PMID- 9152856
TI  - Efficient in vivo gene transfer into the heart in the rat myocardial infarction
      model using the HVJ (Hemagglutinating Virus of Japan)--liposome method.
AB  - The lack of efficient treatment for myocardial infarction remains an unresolved
      problem in the field of cardiovascular disease. Gene therapy may be a potential
      therapeutic strategy for the treatment of myocardial infarction. However, current
      methods of in vivo gene transfer into the heart are limited by their low
      efficiency and/or potential toxicity. In the present study, we developed an
      efficient technique of gene transfer into the intact heart in vivo using the
      Sendai virus (HVJ: Hemagglutinating Virus of Japan)--liposome method. We used the
      beta-galactosidase gene, luciferase gene and human angiotensin converting enzyme
      (ACE) gene as markers. In vivo gene transfer into the rat heart was performed as
      follows: (1) direct injection into the rat heart, (2) incubation within the
      pericardium, and (3) infusion into a coronary artery. Direct injection of the HVJ
      liposome complex containing the beta-galactosidase vector into the rat heart
      resulted in limited staining of beta-galactosidase 3 days after transfection. To
      compare transfection efficiency between "naked" plasmid DNA transfection and the
      HVJ-liposome method, we also transfected the luciferase reporter gene into the
      heart. Luciferase activity was significantly higher in hearts transfected by the
      HVJ-liposome method than that in hearts transfected by direct "naked" plasmid
      transfection (P < 0.01). To confirm the successful gene in the protein level, we
      measured ACE activity in the hearts. Cardiac ACE activity was significantly
      increased in hearts transfected with human ACE gene as compared to hearts
      transfected with control vector (P < 0.01). On the other hand, incubation of HVJ
      liposome complex, containing beta-galactosidase vector, within the pericardium
      resulted in widespread staining of cardiac myocytes and fibroblasts, mainly
      located in several surface layers beneath the pericardium. More importantly,
      widespread stained areas of beta-galactosidase were also observed in the middle
      of the myocardium around the vasa vasorum. We also examined the efficiency of
      gene transfer by the HVJ-liposome method in a rat myocardial infarction model. In
      the infarction model, using the pericardium incubation approach, staining for
      beta-galactosidase was observed in the viable cells around the infarction area.
      Finally, direct infusion of the HVJ complex, containing the beta-galactosidase
      vector, into coronary artery also resulted in widespread staining of beta
      galactosidase in cardiac myocytes around the microvasculature. Using direct
      injection, we found significant injury to the myocardium and severe fibrosis at
      the injection site, whereas no apparent injury was observed using pericardium
      incubation and coronary infusion. There was no evidence of cytotoxicity or
      inflammation caused by the HVJ-liposome complex itself. Overall, we have
      established an efficient in vivo gene transfer method into the heart using the
      HVJ-liposome method. Direct infusion into the coronary artery resulted in
      widespread transfection without damaging the myocytes; incubation within the
      pericardium demonstrated the usefulness of the HVJ-liposome method for studying
      cardiac function and as a means of gene therapy for cardiovascular diseases.

PMID- 9152857
TI  - Functional analysis of myocardial performance in murine hearts overexpressing the
      human beta 2-adrenergic receptor.
AB  - Transgenic mice overexpressing the human beta 2-adrenergic receptor gene were
      compared with wild mice type in terms of cardiac function, using a modified work
      performing isolated murine heart preparation and on-line computer analysis. A
      preload-dependent experiment was performed, in which venous return was gradually
      increased in 5 mmHg increments from 5 mmHg to 25 mmHg. At each preload, aortic
      flow, left atrial pressure and aortic pressure were measured in all hearts, and
      from these parameters stroke volume, contractility, and cardiac index (cardiac
      output divided by body weight in g) were calculated and compared between groups.
      At increasing preload levels, the heart rates ranged from 322 beats/min (+/-29)
      to 369 beats/min (+/-39) in control mice and from 469 beats/min (+/-36) to 540
      beats/min (+/-39) in transgenic mice. Cardiac index increased from 138
      microliters/min/g (+/-13) and 48 microliters/min/g (+/-5) for transgenic and
      control mice, respectively at 5 mmHg preload to 262 microliters/min/g (+/-51) and
      167 microliters/min/g (+/-15), respectively at 20 mmHg preload. The contractility
      in the transgenic mice were significantly increased at lower preload levels
      compared to control mice (1420 mmHg/s +/- 204 v 1187 mmHg/s +/- 127). An increase
      in myocardial adrenergic receptor density (100-200 fold) leads to significantly
      higher indices of cardiac function in transgenic mice compared to control mice.
      The increased heart rate leading to a positive inotropic effect in the hearts of
      transgenic mice is, at least in part, due to the overexpression of adrenergic
      receptors. These findings suggest a possible alternative method of establishing a
      positive chronotropic and inotropic state without the use of pharmacological
      agents.

PMID- 9152858
TI  - Acetylcholine modulates I(f) and IK(ACh) via different pathways in rabbit sino
      atrial node cells.
AB  - The aim of the present study was to examine whether a direct G-protein pathway
      was necessary to explain the depression of the cardiac pacemaker current (I(f))
      by acetylcholine (ACh). Pacemaker current and spontaneous fluctuations of
      muscarinic K+ current (IK(ACh)) were simultaneously measured in sino-atrial (SA)
      node cells isolated from rabbit hearts, using cell-attached and outside-out macro
      patches. The effects of 1 microM ACh, added to the bathing solution, were
      compared on I(f) and on IK(ACh), known to be activated via a direct G-protein
      mechanism. In a cell-attached configuration where cytoplasmic substrates were
      present, ACh depressed I(f) by a negatively directed shift of the open
      probability curve of 7.6 +/- 0.3 mV. ACh never induced modifications in
      spontaneous openings of muscarinic K+ channels. These results indicate that ACh
      added to the external solution is unable to modulate IK(ACh) recorded in the
      membrane-delimited mode, via a G-protein pathway. The ACh depressing effect on
      I(f) is related to changes in second messenger activity. In outside-out
      conditions, with guanosine triphosphate (GTP) added to the pipette solution. ACh
      increased the variance of IK(ACh) fluctuations from 1.66 +/- 0.50 pA2 to 6.60 +/-
      2.05 pA2 (at -120 mV). indicating direct G-protein action. ACh had no effect on
      I(f). It is concluded that in SA node cells, the regulation of I(f) by muscarinic
      receptors does not involve a direct G-protein pathway. ACh depresses I(f) by a
      mechanism that probably implicates reduction of intracellular cAMP production.

PMID- 9152859
TI  - Monensin-induced reversal of positive force-frequency relationship in cardiac
      muscle: role of intracellular sodium in rest-dependent potentiation of
      contraction.
AB  - We have investigated the role of a rest-dependent inotropic factor in determining
      species-related differences in cardiac force-frequency relationships (FFR).
      Isolated rat, rabbit or guinea-pig papillary muscles, as well as guinea-pig
      ventricular myocytes were superfused with 1.8 mM Ca2+ Tyrode. In rat muscles,
      isometric force amplitude decreased, while in rabbit or guinea-pig muscles force
      increased with frequency (0.02-1 Hz). Paired-pulse pacing potentiated contraction
      markedly at all frequencies in rabbit muscles, but not at low frequencies in rat
      muscles. We tested the hypothesis that high intracellular Na+ levels (Nai) are
      responsible for negative FFR. The ionophore monensin increased Nai, reversed the
      FFR of rabbit and guinea-pig muscles from positive to negative, by increasing
      force mostly at low frequencies, and decreased the paired-pulse potentiation of
      contraction at low frequencies. Monensin added during rest also reversed rest
      induced decay. In isolated myocytes, monensin had qualitatively similar effects
      on cell shortening as well as on Cai transients. Monensin also decreased the
      action potential duration (APD) but did not change the pattern of its variation
      with frequency. Cells intracellularly dialyzed with 20 mM Na+ via a patch pipette
      also showed rest potentiation of the Cai transients, in contrast to cells
      dialyzed with 10 mM Na+, which showed rest decay of the transients. APD was also
      shorter in myocytes dialyzed with 20 mM Na+ than in those dialyzed with lower
      Na+. The results indicate that in the presence of high Nai, sarcoplasmic
      reticular Ca2+ load is increased during diastole, possibly via reverse-mode
      Na+/Ca2+ exchange, and therefore that Nai is an important factor determining the
      FFR. In addition, the data suggest that short APDs in preparations showing
      negative FFR may be partly a consequence of increased Nai.

PMID- 9152860
TI  - Protection of ischemic preconditioning is dependent upon a critical timing
      sequence of protein kinase C activation.
AB  - The protection of ischemic preconditioning (PC) appears to be triggered by
      activation of receptors which couple to protein kinase C (PKC) during the brief
      ischemia. Previous experiments, however, suggest that phosphorylation of PKC's
      substrates is not required for the myocytes to enter the preconditioned state.
      Because of the fundamental importance of this observation, the present study was
      designed to stringently test when phosphorylation must occur during a PC
      protocol. We used an in vitro rabbit heart which permitted precise control of the
      timing of exposure to staurosporine (STA), a reversible blocker of PKC's kinase
      activity. In control hearts a 30-min regional coronary occlusion followed by 2 h
      of reperfusion resulted in 31.4 +/- 1.5% infarction of the region at risk, and
      STA (100 nM) had little effect. PC with 5 min of global ischemia and 10 min of
      reperfusion reduced infarction to 11.4% (P < 0.01 v control). STA starting 5 min
      before and ending 5 min after the 5-min PC ischemia did not block protection
      (14.1 +/- 1.7% infarction, P < 0.01 v control). When the PC protocol was changed
      to 5 min ischemia/20 min reperfusion, STA still could not block protection even
      though the infusion continued for 15 min after the PC ischemia. However, when a
      15-min STA infusion was initiated 5 min before the 30-min ischemic period. PC's
      protection was totally blocked. Moreover this late infusion of STA continued to
      block protection even when the PC stimulus was amplified by three cycles of 5-min
      ischemia/10-min reperfusion. These observations indicate that kinase activity is
      not required to put the rabbit heart into a preconditioned state suggesting that
      some process upstream of PKC's kinase is responsible for the triggering and
      memory of PC.

PMID- 9152861
TI  - Anthracyclines enhance tension development in cardiac muscle by direct
      interaction with the contractile system.
AB  - Anthracyclines are highly effective anticancer agents which induce a well
      described but incompletely understood cardiac toxicity. In this study, a direct
      action of several anthracyclines on the force generating mechanism of heart
      muscle preparations is described. To allow discrimination between membrane
      related effects and a direct action of anthracyclines on the actin-myosin
      contractile system, both inner and outer membranes of cardiac fibres were
      permeabilized. All anthracyclines tested in this study [doxorubicin (Dox),
      epirubicin, daunorubicin and idarubicin] showed positive inotropic actions. Dox
      and epirubicin, which are considered the most cardiotoxic drugs of the
      anthracycline family, significantly increased the maximal calcium activated
      tension by 33% (n = 8, P < 0.01) and by 26% (n = 8, P < 0.01) respectively.
      Daunorubicin and idarubicin increased the maximal tension by 12% and 9%
      respectively (P = n.s.). Other chemotherapeutic drugs (Taxol and 5-FU) had no
      effect on maximal tension. To elucidate the mechanism behind this Dox-induced
      increase in maximal tension, calcium sensitivity curves were measured and rigor
      experiments were performed. A small but significant increase in pCa50 value
      (+0.14 +/- 0.03, P < 0.05) was observed only after incubation with 20 microM Dox.
      Dox acted during the transition to force generating cross-bridges as reflected by
      the significant increase in rigor tension (12%, P < 0.05) after preincubation of
      cardiac fibres with Dox. Cycling of cross-bridges is a prerequisite for Dox to
      increase tension because no effect on tension was seen after Dox was added to
      fibres in an established rigor. In summary, anthracyclines increased the maximal
      tension in cardiac muscle fibres by direct interaction with the actin-myosin
      cross-bridges. Changes in calcium sensitivity are unlikely to contribute to the
      observed increase in maximal tension. The rise in tension as is seen in this
      experimental set-up may contribute to destruction of the contractile machinery of
      cardiac muscle. In agreement with this hypothesis is the observation that the
      more cardiotoxic anthracyclines induced the largest increase in maximal tension
      of the cardiac fibres.

PMID- 9152862
TI  - Enhanced expression of Gi-protein precedes the development of blood pressure in
      spontaneously hypertensive rats.
AB  - In the present studies we have investigated if the increased expression of Gi
      alpha proteins reported earlier in heart and aorta from SHR (spontaneously
      hypertensive rats) is the cause or effect of hypertension. The SHRs at various
      ages of the development of blood pressure (3-5 days, 2 weeks, 4 weeks and 8
      weeks) and their age-matched WKY were used for these studies. The expression of
      Gi alpha-2 and Gi alpha-3 (inhibitory guanine nucleotide regulatory protein and
      Gs alpha (stimulatory guanine nucleotide regulatory protein) at protein and mRNA
      level was determined by immunoblotting and Northern blotting technique using
      specific antibodies and cDNA probes. The SHR at early ages up to 2 weeks did not
      show any increase in blood pressure, however it started to go up from 4 weeks.
      The levels of Gi alpha 2 and Gi alpha 3 at protein and mRNA in heart from SHR
      were not different in 3-5 days old SHR as compared to WKY (Wistar-Kyoto rats),
      however, the expression of Gi alpha-2 and Gi alpha-3 protein and mRNA was
      significantly increased in 2 weeks and older SHR. The mRNA level of the catalytic
      subunit type V enzyme was significantly decreased in SHR 2 weeks and later ages
      as compared to their age-matched WKY. On the other hand, the expression of Gs
      alpha was not different in SHR as compared to WKY at all the ages studied. In
      addition, the oxotremorine and C-ANF4-23 (a ring deleted analog of atrial
      natriuretic factor) mediated inhibitions of adenylyl cyclase in hearts and aorta
      were also significantly enhanced in 2 weeks and older SHRs as compared to WKY
      rats, whereas, at younger age of SHR (3-5 days old), no change in the percent
      inhibition of adenylyl cyclase by C-ANF4-23 was observed and oxotremorine was
      unable to inhibit adenylyl cyclase activity. Furthermore, the basal enzyme
      activity and the stimulatory responses of isoproterenol, NECA (N
      ethylcarboxamideadenosine), glucagon and forskolin on adenylyl cyclase were
      significantly decreased at all ages of SHR as compared to WKY. These results
      suggest that the increased expression of genes for Gi alpha-2 and Gi alpha-3,
      decreased expression of type V enzyme mRNA and decreased cAMP levels precedes the
      development of blood pressure and may participate in the pathogenesis of
      hypertension.

PMID- 9152863
TI  - Regional and age-related differences in mRNA composition of intracellular Ca(2+)
      release channels of rat cardiac myocytes.
AB  - We investigated the mRNA distribution of three different ryanodine receptors
      (RyR) and of the intracellular Ca(2+)-release channel/inositol 1,4,5
      trisphosphate receptor (IP3R) type 1 in the rat heart during development and
      aging. In situ hybridization analysis shows that RyR1 mRNA is never expressed in
      the heart at any of the stages examined: RyR2 mRNA is detectable in
      cardiomyocytes in the early embryonic stages, whereas RyR3 mRNA accumulates in
      cardiomyocytes around birth. IP3R mRNA appears at first in the primitive atrium
      at embryonic day 11 and in subsequent stages it is detectable also in a minor
      population of ventricular myocytes, which presumably correspond to conduction
      system precursors. In the adult heart, no apparent difference in hybridization
      signal intensity is observed between atrial and ventricular working myocytes
      either with RyR2, RyR3 or IP3R cRNA probes, except for myocytes of the heart
      conduction system, which differ from working myocytes in the intensity of the
      hybridization signals for each probe. Additional differences are detected in the
      senescent heart with the IP3R cRNA probe, which hybridizes with atrial myocytes
      stronger than with ventricular ones. RNase protection analysis confirms the
      temporal differences in RyR2 and RyR3 transcript accumulation observed during
      heart development and reveals a significant increase of IP3R mRNA in the atrial
      myocardium during aging. Thus, the composition of intracellular Ca(2+)-release
      channel mRNAs of the rat heart shows temporal and regional variations: such
      changes might reflect important differences in transcriptional regulation of
      these genes among myocytes.

PMID- 9152864
TI  - Effects of calcium channel antagonists on Ca2+ transients in rat and canine
      cardiomyocytes.
AB  - First-generation Ca2+ channel antagonists depress myocardial contractility, but
      many of the newer Ca2+ channel blockers have a high degree of "vascular
      selectivity". This study compares the effects of the Ca2+ antagonists felodipine,
      amlodipine, mibefradil, verapamil and nifedipine, and the Ca2+ channel agonist.
      (S)(-)-Bay K-8644 on Ca2+ transient amplitudes in fura-2/AM-loaded rat and canine
      ventricular cardiomyocytes. At 10(-11) and 10(-10) M, felodipine increased
      [Ca2+]i transient amplitudes by 10-25% in field-stimulated fura-2-loaded cells
      from both species while at 10(-6) M it depressed [Ca2+]i transients by 80%.
      Mibefradil increased [Ca2+]i transient amplitudes by 16% at 10(-11) and 10(-10) M
      and decreased the transients by 25% at 10(-6) M. The calcium channel agonist,
      (S)(-)-Bay K-8644 increased [Ca2+]i transient amplitudes at 10(-10)-10(-6) M
      (maximally 37% at 10(-7) M) but depressed [Ca2+]i transients by 10% at 10(-5) M.
      Nifedipine was inhibitory at all concentrations tested (10(-11)-10(-6) M) in
      canine myocytes, but in rat cells. 10(-10) M nifedipine increased [Ca2+]i
      transient amplitudes by 37%. All concentrations of verapamil and amlodipine (10(
      11)-10(-6) M) depressed [Ca2+]i transients in both rat and canine myocytes. We
      conclude that: (1) felodipine and mibefradil may be positive rather than negative
      inotropes at low concentrations, which are therapeutically relevant: and (2) low
      concentrations of nifedipine may have a positive inotropic effect in the rat but
      not the dog heart.

PMID- 9152865
TI  - Transplantation-induced atrophy of normal and hypertrophic rat hearts: effect on
      cardiac myocytes and capillaries.
AB  - Changes in tissue structure of hearts undergoing atrophy following heterotopic
      isotransplantation were studied. Both normal and hypertrophic hearts were used,
      originating from male and female rats. Aortic constriction produced in newborn
      rats, resulted in an 86 and 155% increase of left ventricular mass in male and
      female rats, respectively. On day 50, control and experimental animals were
      killed, half of their hearts were analysed morphometrically, while remaining
      hearts were transplanted into the abdominal cavity of recipient rats.
      Transplantation resulted in significantly decreased cardiac mass in control
      hearts (approximately 50% decrease compared to values at transplantation), and an
      even more pronounced decrease in hypertrophic hearts. Cardiac hypertrophy was
      characterized by significant decreases in capillary and myocyte densities. While
      myocyte density simply reflected changes in cell size, evidence for additional
      capillary growth was found (the aggregate length of capillaries per left
      ventricle increased by 57-88%). Cardiac atrophy resulted in increased capillary
      density, despite evidence of some capillary involution in transplanted hearts
      (aggregate length of capillaries decreased by 30-35% and 52-64% for transplants
      of normal and of hypertrophic hearts, respectively). Myocyte density increased
      due to a proportional decrease in the size of cardiac myocytes. In transplanted
      hearts, an increasing number of myocytes containing nuclei located close to the
      nearest capillary, suggests that changes in myocyte size are not symmetrical. The
      present study demonstrated the remarkable plasticity of the heart in neonatal
      animals; they were capable of large increases and decreases in cardiac mass
      within a few weeks, with more pronounced changes in female rats. These changes
      were accompanied by changes in myocardial structure, indicating some capillary
      growth in cardiac hypertrophy, and involution of coronary capillaries in cardiac
      atrophy.

PMID- 9152866
TI  - The ischemia-selective KATP channel antagonist, 5-hydroxydecanoate, blocks
      ischemic preconditioning in the rat heart.
AB  - Although the KATP channel has been demonstrated to be involved in ischemic
      preconditioning (IPC) in most species, controversy still exists as to the role of
      this channel as a mediator of PC in the rat heart. Previously, the authors'
      laboratories have shown that glibenclamide blocks IPC in the intact rat heart, in
      a time-dependent manner; however, since glibenclamide has been shown to have non
      selective effects unrelated to KATP channel blockade, a structurally dissimilar
      and ischemia-selective KATP channel blocker, 5-hydroxydecanoate (5-HD), was used
      to further elucidate the role of KATP channels in mediating IPC in the rat heart.
      Anesthetized, open-chested Sprague-Dawley rats were subjected to one of four
      protocols. In Group I, control (C), rats were subjected to 30 min of left
      coronary artery occlusion and 90 min of reperfusion. In Group II, IPC was
      elicited by 1 x 5 min occlusion followed by 10 min of reperfusion, prior to the
      30 min occlusion and 90 min reperfusion periods, 5-HD (5 mg/kg, i.v.) was given
      15 min prior to the 30 min occlusion period in non-preconditioned animals, or
      given 15 min prior to IPC (5-HD+IPC) (Groups III and IV, respectively). Infarct
      size (IS), as a percentage of the area at risk (AAR), was determined by
      triphenyltetrazolium staining. Ischemic preconditioning produced a marked
      reduction in infarct size (47.5 +/- 3.8% to 7.9 +/- 1.9%, *P < 0.01), which was
      completely abolished by 5-HD (50.5 +/- 2.6%). These data further suggest that the
      opening of KATP channels is an important component of IPC in the intact rat
      heart, similar to that observed in other species.

PMID- 9152867
TI  - Methoprene affects the rotation of the male terminalia of Aedes aegypti
      mosquitoes.
AB  - The rotation of the male terminalia of Aedes aegypti mosquitoes was investigated
      with chemical surgical, and mechanical methods. Neither decapitation nor ventral
      nerve cord transection affected the postemergence rotation, but methoprene
      administered to 4th-instar larvae and early instar pupae slowed rotation
      significantly and, in the case of pupal treatment, also interfered with
      successful insemination. Methoprene appeared to interfere with the developmental
      maturation of the cross muscles located between the 7th and 8th abdominal segment
      and postemergence nervous or humoral signals did not appear to affect this
      rotation.

PMID- 9152868
TI  - Anopheline mosquitoes of the western province of Papua New Guinea.
AB  - A survey of the Anopheles species of Western Province, Papua New Guinea, was made
      in April-May 1992. A total of 6,427 specimens was collected from 74 sites within
      the province using carbon dioxide-baited light traps and larval sampling. Eleven
      species were identified using morphological characteristics, allozyme analysis,
      and species-specific DNA probes. These were, in order of prevalence: Anopheles
      farauti 2 (51 sites), An. bancroftii (17 sites), An. farauti s. s. (16 sites),
      An. longirostris (9 sites), An. farauti 3 (7 sites), An. punctulatus (4 sites),
      An. koliensis (4 sites), Anopheles sp. near punctulatus (4 sites), An.
      meraukensis (4 sites), An. farauti 4 (3 sites), and An. novaguinensis (2 sites).
      Members of the An. farauti complex made up 93.3% of the specimens collected with
      An. farauti 2 being the most abundant and widespread species inland and An.
      farauti s. s. the dominant species on the coast. The abundance and distribution
      of the species are discussed.

PMID- 9152869
TI  - Methods of testing and analyzing excito-repellency responses of malaria vectors
      to insecticides.
AB  - A new test system that includes an excito-repellency test box, test procedures,
      and statistical treatment of data is described. The method consists of enclosing
      25 mosquitoes in an exposure chamber lined with insecticide-treated or untreated
      (control) test papers. Each chamber has a single portal for mosquitoes to escape
      to a receiving cage, and numbers escaping are manually recorded at 1-min
      intervals. The exposure chamber accommodates a screened, 2nd chamber that, when
      placed in the exposure chamber, prevents the mosquitoes from making physical
      contact with test papers. A full assay utilized one exposure chamber that permits
      physical contact with insecticide-treated papers, one chamber that permits
      physical contact with control papers, one chamber that prevents physical contact
      with insecticide-treated papers, and a 4th chamber that prevents contact with
      control papers. After insecticide exposure, test populations are held for
      observations on 24-h mortalities. A survival analysis approach is described for
      estimating mosquito escape rates and for comparing differences in mosquito escape
      rates, with or without physical contact with insecticide, among populations,
      insecticides, and doses of insecticide.

PMID- 9152870
TI  - Evaluation of Caribbean strains of Macrocyclops and Mesocyclops
      (Cyclopoida:Cyclopidae) as biological control tools for the dengue vector Aedes
      aegypti.
AB  - Fifteen Caribbean strains of copepods were assessed for their predation ability
      against mosquito larvae. Macrocyclops albidus from Nariva. Mesocyclops
      aspericornis from Oropouche, and Mesocyclops longisetus from E1 Socorro,
      Trinidad, were most effective against Aedes aegypti but not against Culex
      quinquefasciatus. Mesocyclops longisetus and Me. aspericornis prevented any
      mosquito survival over 25 wk of observation despite weekly challenges with Ae.
      aegypti. The copepods were tolerant to dosages of the insecticide temephos that
      are usually toxic to mosquito larvae. This indicated that copepods could be
      incorporated into an integrated control system. To determine whether pathogenic
      microbes might be introduced with copepods into drinking water, microbial studies
      were done on the copepods. These showed the presence of only Aeromonas sobria,
      Pseudomonas sp., Alcalignes sp., and gram-positive bacilli. Although none of
      these are highly pathogenic to humans, the application of these copepods has not
      yet been recommended for use in drinking water.

PMID- 9152871
TI  - Attractant resting boxes for rapid collection and surveillance of Aedes aegypti
      (L.) inside houses.
AB  - Three different resting station designs made of cardboard covered with black
      cloth were evaluated for their attractiveness to Aedes aegypti populations
      resting inside houses in Thailand. Box designs attracted more females (but not
      males) than an open-panel design. Thirty to 60% of all adult Ae. aegypti resting
      inside houses were collected by aspirating from 2-4 resting boxes placed inside
      houses. Tall boxes (90 cm) did not attract more females or males than short boxes
      (45 cm). Forty-two percent more females (but fewer males) were attracted to boxes
      when oviposition bowls were placed inside the boxes. Four boxes per house
      attracted 32% more mosquitoes than two boxes. Aspirating from artificial resting
      stations is an efficient and rapid method for sampling male and teneral,
      bloodfed, and gravid female Ae. aegypti resting inside houses.

PMID- 9152872
TI  - Use of generalized regression tree models to characterize vegetation favoring
      Anopheles albimanus breeding.
AB  - We propose the use of generalized tree models (GTMs) to analyze data from
      entomological field studies. Generalized tree models can be used to characterize
      environments with different mosquito breeding capacity. A GTM simultaneously
      analyzes a set of predictor variables (e.g., vegetation coverage) in relation to
      a response variable (e.g., counts of Anopheles albimanus larvae), and how it
      varies with respect to a set of criterion variables (e.g., presence of
      predators). The algorithm produces a treelike graphical display with its root at
      the top and 2 branches stemming down from each node. At each node, conditions on
      the value of predictors partition the observations into subgroups (environments)
      in which the relation between response and criterion variables is most
      homogeneous.

PMID- 9152873
TI  - Age-related changes in development of the accessory glands of male Anopheles
      albimanus.
AB  - This study presents the effects of age on the accessory glands of male Anopheles
      albimanus. The paired oval glands have an outer muscular layer and an inner layer
      of columnar secretory cells. Male pupae have uniformly long columnar cells and
      contain only traces of male accessory gland substance (MAGS). In newly emerged
      males, the posterior section of the gland has short columnar cells that produce
      an opaque, white MAGS consisting of one type of secretory granules. The anterior
      section has long columnar cells that produce yellow as well as white MAGS. In 84
      h-old males, the columnar cells are short throughout the gland and the glands are
      replete with both forms of MAGS. The amount of MAGS may control secretory
      activity of the columnar cells by a feedback mechanism.

PMID- 9152874
TI  - Effects of two insect growth regulators on the susceptibility of Aedes aegypti
      (Diptera:Culicidae) to Molinema dessetae (Nematoda:Filarioidea).
AB  - The effects of 2 growth regulators, diflubenzuron (DFB) and OMS 2017, on the
      ability of females Aedes aegypti to become infected with Molinema dessetae was
      studied under laboratory conditions. OMS 2017 and DFB had no effect on either the
      amount of blood ingested or the microfilarial load. The infective potential of
      females that survived DFB treatment was significantly greater than untreated
      females, but there was no difference between OMS 2017-treated and control
      females. The percentage of infective larvae in the head after OMS 2017 and DFB
      treatments was significantly greater than for control females. Insect growth
      regulators appear to affect the vectorial competence of mosquitoes, and these
      results indicate the need for preliminary studies before these compounds are used
      in large-scale control programs.

PMID- 9152875
TI  - Test of a mosquito eggshell isolation method and subsampling procedure.
AB  - Production of Aedes vigilax, the common salt-marsh mosquito, can be assessed by
      determining eggshell densities found in soil. In this study, 14 field-collected
      eggshell samples were used to test a subsampling technique and compare eggshell
      counts obtained with a flotation method to those obtained by direct examination
      of sediment (DES). Relative precision of the subsampling technique was assessed
      by determining the minimum number of subsamples required to estimate the true
      mean and confidence interval of a sample at a predetermined confidence level. A
      regression line was fitted to cube-root transformed eggshell counts obtained from
      flotation and DES and found to be significant (P < 0.001, r2 = 0.97). The
      flotation method allowed processing of samples in about one-third of the time
      required by DES, but recovered an average of 44% of the eggshells present.
      Eggshells obtained with the flotation method can be used to predict those from
      DES using the following equation: DES count = [1.386 x (flotation count)0.33 -
      0.01]3.

PMID- 9152876
TI  - SEM examination of the eggs of five British Aedes species.
AB  - Ultrastructure descriptions are given of the eggs of five British Aedes species,
      namely Aedes (Aedes) cinereus Meigen, Aedes (Ochlerotatus) cantans (Meigen),
      Aedes (Ochlerotatus) punctor (Kirby), Aedes (Ochlerotatus) detritus (Haliday),
      and Aedes (Ochlerotatus) rusticus (Rossi). Eggs of the first 4 species are
      broadly cigar/boat-shaped, with those of Ae. cinereus being characteristically
      long and narrow, in contrast to the overall shape of Ae. rusticus, which is quite
      distinct, being in profile almost subtriangular with rounded corners, and is
      completely species-diagnostic. In Ae. cantans, Ae. punctor, and Ae. rusticus
      there is usually a single large tubercle in each chorionic cell and there is
      little, if any, difference in the sculpturing of the ventral and dorsal surfaces,
      whereas in Ae. detritus each cell contains more than 20 tubercles, and in Ae.
      cinereus there are usually 6 tubercles per cell ventrally, but dorsally there are
      no tubercles or distinct cells but numerous cone-shaped papillae. All 5 species
      can be separated from each other by SEM examination of their chorionic patterns.

PMID- 9152877
TI  - Efficacy of carbon dioxide, 1-octen-3-ol, and lactic acid in modified Fay-Prince
      traps as compared to man-landing catch of Aedes aegypti.
AB  - The attractants 1-octen-3-ol and lactic acid significantly decreased catches of
      Aedes aegypti in Townsville, Australia, by 50% in a controlled laboratory
      environment and by 100% in the field when compared to carbon dioxide baited
      bidirectional Fay-Prince trap catches. Evaluation of an omnidirectional
      alteration on a bidirectional Fay-Prince trap revealed no significant improvement
      in catch size when compared to both the bidirectional trap and man-landing catch
      (MLC). Cumulative evening MLC (1730-2000 h) was twice that of the morning MLC
      (0600-0830 h), which has implications on the precise estimation of the man-biting
      rate. The MLC sampling method is shown to be a quick, simple, effective and cheap
      alternative to expensive traps in areas not currently experiencing arbovirus
      transmission.

PMID- 9152878
TI  - Host preference of mosquitoes in Bernalillo County, New Mexico.
AB  - Host preference of mosquitoes was determined using animal-baited traps. Hosts
      used in the study were cattle, chickens, dogs, and horses. Ten mosquito species
      representing 4 genera were collected from the animal-baited traps. Aedes vexans,
      Aedes dorsalis, Culex quinquefasciatus. Culex tarsalis, and Culiseta inornata
      were used as indicator species for data analysis. Greater numbers of Ae. vexans,
      Ae. dorsalis, and Cs. inornata were collected from cattle and horses than from
      chickens or dogs. In addition, engorgement rates were higher on mammals than on
      chickens. Engorgement and attraction data for Cx. quinquefasciatus suggested a
      preference for chickens and dogs over cattle and horses. A slight preference for
      chickens and dogs was seen with Cx. tarsalis, but the degree of host preference
      of Cx. tarsalis was less than that in either Ae. vexans or Cx. quinquefasciatus.

PMID- 9152879
TI  - Ultrastructure of the eggs of Culicoides circumscriptus, Culicoides gejgelensis,
      and Culicoides imicola (Diptera:Ceratopogonidae).
AB  - The eggs of Culicoides circumscriptus Kieffer, Culicoides gejgelensis Dzhafarov,
      and Culicoides imicola Kieffer collected in Israel are described and illustrated
      by scanning electron micrographs. Eggs of all 3 species were morphologically
      similar, generally sausage- or cigar-shaped, with slight dorsal-ventral curvature
      and longitudinal rows of tubercle pillars covered with a thin adhesive layer.
      Tubercle pillars were scarce on C. circumscriptus and C. imicola eggs, but were
      common on C. gejgelensis eggs, forming longitudinal plastrons with an associated
      hydrofuge meshwork. All 3 species had micropyle domes and associated aeropyles at
      the anterior end of their eggs.

PMID- 9152880
TI  - A spray management valve for hand-compression sprayers.
AB  - The commercially available spray management valve provided consistent flow rates
      when used with hand-compression sprayer systems. The 15-psi spray management
      valve maintained a constant flow rate of 180, 150, and 155 ml/min in combination
      with a fine 45 degrees flat fan nozzle and Hudson. B&G, and Chapin hand
      compression sprayers, respectively. The 30-psi spray management valve maintained
      a constant flow rate and adequate spray-on time when combined with the coarse
      flat fan nozzle for each of the 3 hand-compression sprayers tested.

PMID- 9152881
TI  - Use of Bactimos briquets (B.t.i. formulation) combined with the backswimmer
      Notonecta irrorata (Hemiptera:Notonectidae) for control of mosquito larvae.
AB  - The efficacies of Bacillus thuringiensis var. israelensis (Bactimos briquets) and
      the backswimmer Notonecta irrorata were evaluated both individually and in
      combination to control mosquito larvae in plastic containers in Monterrey,
      Mexico. The combined strategy proved to be the most effective one.

PMID- 9152882
TI  - An electrostatic backpack sprayer: potential for mosquito control.
AB  - A Southwest Electrostatic Sprayers, Inc., nozzle was configured to a Hudson
      PortaPak backpack. A test was run to compare deposition of BVA no. 13 oil by the
      electrostatic nozzle to a standard nonelectrostatic nozzle as collected by Teflon
      slides. Results indicate that 100% greater deposition occurred with the
      electrostatic nozzle.

PMID- 9152883
TI  - A thermal heat summation model to predict the duration of the gonotrophic cycle
      of Culiseta melanura in nature.
AB  - This study determined the effect of temperature on the gonotrophic cycle of
      Culiseta melanura and developed a thermal heat summation model to calculate its
      duration under field conditions. A colony of Cs. melanura was used from New
      Jersey (F13-F17 generation) and the length of the gonotrophic cycle was observed
      at 2, 10, 16, 22, 28, 32 and 34 degrees C. None of the mosquitos survived at 2
      degrees C or 34 degrees C and none laid fertile eggs at 32 degrees C. A linear
      regression analysis on the data showed that the thermal minimum for ovarian
      development was 6.4 degrees C and 95.87 degree days were required above 6.4
      degrees C to complete one gonotrophic cycle. A thermal heat summation model is
      presented to allow calculation of the duration of the gonotrophic cycle under
      field conditions when average temperatures are known.

PMID- 9152884
TI  - Establishment of a free-mating colony of Anopheles albitarsis from Brazil.
AB  - The establishment of a free-mating colony of Anopheles albitarsis sensu siricto,
      a member of the Anopheles albitarsis complex, is described. Groups of females
      from the F5, F6, and F11 generations were examined, and the percent inseminated,
      mean number of eggs oviposited, and percent hatch discussed. The colony has been
      continued through 18 generations, with larval development averaging 10 days, and
      larval mortality ranging between 20 and 30%.

PMID- 9152885
TI  - Mosquitofish in control programs.

PMID- 9152886
TI  - Mosquito control with Gambusia affinis.

PMID- 9152887
TI  - Pseudoreplication: what does it mean, and how does it relate to biological
      experiments?

PMID- 9152888
TI  - Advances in the treatment of HIV: hope and challenge.

PMID- 9152889
TI  - Complementary and alternative medicine and HIV/AIDS. Part II: Selected literature
      review.
AB  - People with HIV/AIDS are using complementary and alternative medicine (CAM) to
      improve general health, prevent opportunistic infections, treat symptoms, and
      reduce side effects from biomedical treatments. This paper reviews the research
      and narrative literature on CAM use in people with HIV/AIDS and covers (1)
      nutrition; (2) exercise; (3) traditional and ethno-medicine; (4) miscellaneous
      products; and (5) psychosocial interventions.

PMID- 9152890
TI  - Satisfaction with nursing care: a comparison of patients with HIV/AIDS, non
      HIV/AIDS infectious diseases, and medical diagnoses.
AB  - The purpose of this study was to describe patients' perceptions of nursing care
      and compare those perceptions based on patients' diagnoses (HIV/AIDS, non
      HIV/AIDS infectious diseases, and medical diagnoses). One hundred forty-two
      patients on five units in a major medical center were surveyed using the Patient
      Satisfaction Instrument. In addition, 126 staff nurses completed the AIDS
      Vulnerability Survey. Results of data analysis indicated a statistically
      significant difference in patient satisfaction with nursing care among patients
      in the medical group compared to patients in the HIV/AIDS group, with the medical
      group being more satisfied with their nursing care. Further, there was a
      statistically significant difference across units between nurses' knowledge,
      attitude, and fear. In spite of their knowledge base related to HIV/AIDS, nurses
      felt vulnerable when providing care to this population, thus perpetuating fear
      and negative attitudes. Additional research into the dynamics of these
      relationships is imperative as we continue to see increases in the number of
      patients with HIV/AIDS.

PMID- 9152891
TI  - HIV, self-transcendence, and quality of life.
AB  - Self-transcendence is a developmental characteristic that expands one's
      boundaries of the self to take on broader life perspectives, activities, and
      purposes that help one discover or make meaning of one's life. However, no
      quantitative studies were found in the research literature that focused on self
      transcendence or on the relationship between self-transcendence and quality of
      life in people infected with HIV. To examine these variables in this population,
      46 HIV-positive subjects completed Reed's Self-Transcendence Scale and Ferrans
      and Powers' Quality of Life Index. The results demonstrated that overall self
      transcendence for this sample was relatively high; quality of life was higher
      than that reported in previous research; and there were some significant group
      differences among the three HIV clinical categories.

PMID- 9152892
TI  - Exploring a life history of HIV disease and self-caring: Alfredo's story.
AB  - Alfredo's story is part of a larger phenomenological study of nursing, self care,
      and HIV disease that incorporated the anthropological tradition of reconstructing
      a life-story in the person's own words. This exemplar emphasizes Alfredo's shifts
      perspective organized around three turnings, or shifts in perspective, which are
      illustrated with narrative text and discussed. The three turnings include
      becoming HIV-infected, becoming a positive force, and reclaiming self.
      Implications for nursing include the importance of story telling in life history,
      the value of knowing the patient as a person, the positive impact of negative
      events, and the educational impact of a paradigm case.

PMID- 9152893
TI  - Accessing HIV-infected research subjects: the need for collaboration.

PMID- 9152894
TI  - Prevention versus treatment: an ongoing dilemma.

PMID- 9152895
TI  - Stereotypes.

PMID- 9152896
TI  - Values influencing nursing practice: responses from neonatal nurses.
AB  - PURPOSE: An analysis of narrative comments from neonatal nurses to illustrate the
      values that motivate behavior in the practice setting. DESIGN: A descriptive
      study using content analysis of written, narrative text data. PARTICIPANTS: A
      self-selected subsample (N = 97) of a larger random sample of the membership of
      the National Association of Neonatal Nurses (NANN). MAIN OUTCOME MEASURES: The
      application of philosophical concepts of human relationships, patient need,
      keeping promises, human dignity, and unrestricting circumstances in the neonatal
      care setting. RESULTS: Individual participants made cognitive choices related to
      the application of conceptual ideals of the profession to the practice setting.
      However, there was a lack of congruence between what the individual nurse
      believes is important or good and the behavior enacted in the practice setting.
      CONCLUSION: As a discipline, nursing needs to identify and implement strategies
      that support proactive accountable nursing practice consistent with the
      philosophical foundation of the profession.

PMID- 9152897
TI  - Teaching teens to cope: coping skills training for adolescents with insulin
      dependent diabetes mellitus.
AB  - PURPOSE: To review the potential use and application of coping-skills training in
      teaching adolescents effective ways of managing the stressors related to living
      with diabetes mellitus. POPULATION: Adolescents ages 13 to 20 with insulin
      dependent diabetes mellitus who are participating in the research project,
      "Nursing Intervention to Implement DCCT Therapy in Youth" at Yale University
      School of Nursing. CONCLUSIONS: Teaching adolescents with diabetes mellitus to
      use appropriate coping skills may help them cope with the day-to-day management
      of the illness and aid in long-term adaptation. PRACTICE IMPLICATIONS: Research
      has suggested that the use of effective coping skills may aid in healthy long
      term adaptation to diabetes mellitus. Thus, nurses caring for adolescents with
      this illness should teach and be role models for these effective coping
      strategies.

PMID- 9152898
TI  - Daytime and nighttime wetting in children: a review of management.
AB  - PURPOSE: To describe the types of voiding dysfunction common to children, review
      pertinent literature on enuresis, discuss treatment options, and explore the
      nurse's role in identifying and managing children with voiding difficulties.
      POPULATION: Children beyond the age of normal toileting who continue with
      uncontrolled urination either during the day, at night, or both. CONCLUSION:
      Inappropriate urination in children is a common occurrence. Ninety-five percent
      of voiding problems are functional, and 5 percent represent pathologic
      conditions. There is widespread misunderstanding among parents, teachers, and
      primary care providers on the causes and management options for these children.
      PRACTICE IMPLICATIONS: Pediatric nurses are in key positions to identify children
      with voiding problems. Once the problem has been acknowledged, nurses can assess
      the problem and its impact on the family; educate parents, children, and others
      regarding causes; discuss management options; and refer children for medical
      intervention when necessary.

PMID- 9152899
TI  - Use of a projective technique to assess young children's appraisal and coping
      responses to a venipuncture.
AB  - PURPOSE: To examine the appraisal, emotional and coping responses of young
      hospitalized children to three phases of a venipuncture procedure. DESIGN:
      Exploratory, descriptive. SETTING: Pediatric unit of a community hospital.
      PARTICIPANTS: Four- to 9-year-old hospitalized children (N = 45). MAIN OUTCOME
      MEASURES: Data were obtained by means of a projective technique and interview
      format. Content analysis of the children's responses was guided by the use of
      four published measures (appraisal, behavioral coping strategies, cognitive
      coping strategies, and helpful interventions). RESULTS: The children appraised
      each phase of the venipuncture as a threat, a benefit, or a threat/benefit. The
      most frequently identified behavioral coping strategies were self-protective
      behaviors and returning to normal activities. The most frequently identified
      cognitive coping behaviors were reality-oriented working through, emotion
      regulating cognitions, and diversionary thinking. The children reported the most
      helpful intervention as providing information about the event. CONCLUSION: The
      children were able, through a projective technique, to appraise a venipuncture
      and spontaneously identify many cognitive and behavioral coping strategies and
      interventions to help them manage a venipuncture.

PMID- 9152900
TI  - Pain management in the hospitalized infant.

PMID- 9152901
TI  - 1997 SCVIR Gary J. Becker Young Investigator Award paper. A transluminally
      created abdominal aortic aneurysm model.
AB  - PURPOSE: To develop a stable, transluminally created abdominal aortic aneurysm
      (AAA) within a live animal model. MATERIALS AND METHODS: Eight mongrel dogs were
      utilized to evaluate a new, catheter-based technique for the creation of an AAA.
      With use of a standard angioplasty balloon and a balloon-expandable intravascular
      metallic stent, the infrarenal abdominal aorta was overdilated to twice its
      measured diameter into a fusiform shape AAA in eight dogs. At 30 days,
      aortography was performed, the dogs were killed, and the aorta was resected and
      evaluated for histopathology. RESULTS: Seven of the eight dogs that underwent
      transluminal AAA creation survived the initial procedure. A stable, fusiform AAA
      was successfully created in these seven dogs. At 30 days, repeat angiography and
      histologic examination confirmed that the seven AAAs were still twice the
      diameter of the normal aorta (a four-fold increase in luminal area), that the
      branch arteries remained patent, and that the lumen was endothelialized. One of
      the eight dogs was killed 9 hours after the procedure because of inability to
      awaken from anesthesia. Gross and histopathologic results in this one dog also
      demonstrated an intact aorta containing an AAA. CONCLUSIONS: A stable, infrarenal
      AAA model can be successfully created in the canine species with use of standard
      catheter-based techniques and equipment. This model can be used to test emerging
      endovascular treatments of AAA.

PMID- 9152902
TI  - Percutaneous intervention for permanent hemodialysis access: a review.

PMID- 9152903
TI  - Approach to the patient with diabetes undergoing a vascular or interventional
      procedure.

PMID- 9152904
TI  - Acute rupture of the descending thoracic aorta: repair with use of endovascular
      stent-grafts.
AB  - PURPOSE: To describe the use of endovascular stent-grafts to treat acute ruptures
      of the descending thoracic aorta as an alternative to surgery in high-risk
      patients. MATERIALS AND METHODS: From July 1992 to August 1996, 95 patients
      underwent stent-grafting of the descending thoracic aorta for a variety of
      lesions. Of these, 11 patients with acute (< or = 7 days) rupture from aneurysms
      (n = 8) or trauma (n = 3) underwent repair with use of endovascular stent-grafts.
      Rupture was confirmed with preoperative imaging studies and occurred in the
      mediastinum (n = 9), the pleural space (n = 1), or the lung (n = 1). All patients
      were considered high surgical risk due to generalized cardiopulmonary disease
      and/or previous thoracotomies. Stent-grafts were constructed from Z stents
      covered with polyester fabric and delivered through a catheter under fluoroscopic
      control from a remote access site. RESULTS: Stent-graft deployment was successful
      in all patients. There were no complications of perigraft leak, stent migration,
      paraplegia, or intraoperative death. Two patients died in the follow-up period:
      one of ventricular perforation during unrelated thoracic surgery for tumor
      resection (day 1) and one of cardiac arrest (day 28). All others are alive (mean
      follow-up, 15.1 months). CONCLUSION: For acute rupture of the thoracic aorta,
      endovascular stent-graft repair is technically feasible and may be a therapeutic
      alternative to a surgical interposition graft in patients considered high risk
      for conventional thoracotomy. Long-term studies are necessary to determine the
      role of stent-grafts in preventing future aortic rupture.

PMID- 9152905
TI  - Short-term results with use of the Amplatz thrombectomy device in the treatment
      of acute lower limb occlusions.
AB  - PURPOSE: To evaluate the clinical efficacy of the Amplatz device for the
      treatment of acute occlusions of the lower limb arteries. MATERIALS AND METHODS:
      Forty patients with acute occlusion of the lower limb arteries (3 hours to 8
      days; mean, 2 days) were treated using the Amplatz clot macerator. Acute
      thrombotic lower limb occlusion was due to an embolic event in 32 patients and to
      atherosclerotic disease in eight patients. RESULTS: Complete success, with
      complete clearing of thrombotic material without an adjunctive procedure, was
      achieved in 75% (30 of 40) of the patients. Mean thrombectomy time in these
      patients was 75 seconds. Partial success, with incomplete clearing of the
      thrombus, requiring additional procedures such as local thrombolysis,
      angioplasty, or atherectomy, was achieved in 20% (eight of 40) of the patients.
      The Doppler index increased significantly (P < .001) from .45 before intervention
      to .96 after intervention. There were two failures (5%). No major complications
      occurred. CONCLUSION: Mechanical thrombectomy with use of the Amplatz device is a
      promising approach for quick recanalization of acute peripheral thromboembolic
      occlusions. Further studies are needed to prove the long-term patency after
      mechanical thrombectomy with use of this device.

PMID- 9152906
TI  - Treatment of chronic iliac artery occlusions by means of percutaneous
      endovascular stent placement.
AB  - PURPOSE: A retrospective evaluation of outcomes in patients with chronic iliac
      occlusions treated with insertion of metallic endovascular stents, without
      previous thrombolysis, on an intention-to-treat basis. MATERIALS AND METHODS:
      Seventy-two patients with chronic iliac occlusion underwent attempted stent
      placement from either the ipsilateral or contralateral femoral artery. There were
      49 men and 23 women. Mean age was 63.1 years (range, 39-88 years). A total of 89
      stents were deployed in 67 patients. Follow-up was from 24 to 69 months (mean,
      37.5 months). RESULTS: Stents were successfully deployed in 67 patients (93%),
      with two early failures, giving a primary success rate of 90%. There were five
      significant and four insignificant procedural complications. There were four late
      failures (all within the first year) and four non-stent-related deaths.
      CONCLUSION: Endovascular stent placement offers an alternative to surgery in the
      treatment of chronic iliac occlusions.

PMID- 9152907
TI  - Valvectomy with use of a percutaneous directional atherectomy catheter in failing
      in situ saphenous vein grafts.

PMID- 9152908
TI  - Percutaneous endoluminal stent placement for traumatic occlusion of the internal
      jugular vein.

PMID- 9152909
TI  - Working with laboratory animals: general principles and practical considerations.
AB  - Laboratory animals play an indispensable role in research discovery and
      technological advances, and they will continue to yield basic, exciting, and
      prodigious information that can enrich the future of people and other animals.
      For both ethical and scientific reasons, all-individuals whose work requires the
      use of laboratory animals must take the time to conduct a thorough review of the
      literature to determine what animal models are available and which are the most
      relevant, and they must learn and understand the uniqueness of the selected
      species, breed, and strain. Scientists have the privilege, but not the right, to
      use animals as experimental subjects. This privilege must not be abused.
      Therefore, it is imperative that before working with any laboratory animal, you
      know your "subject."

PMID- 9152910
TI  - Smooth muscle cell proliferation in response to co-culture with venous and
      arterial endothelial cells.
AB  - PURPOSE: The critical role of endothelial cells (ECs) in arterial disease is well
      established, but little is known of their role in venous disease. Previous
      studies suggest inherent differences between arteries and veins: arterial
      stenoses demonstrate a large lipid component, whereas hemodialysis-related venous
      stenoses are characterized by marked smooth muscle cell (SMC) proliferation. This
      study compares effects of venous versus arterial ECs on SMC proliferation in co
      culture. MATERIALS AND METHODS: Human saphenous vein ECs (HSV-ECs) or human
      aortic ECs (HA-ECs) were cultured on the underside of 10-micron, porous
      polycarbonate membranes and allowed to grow to confluence for 48 hours. After EC
      confluence, human aortic SMCs (HA-SMCs) were cultured on the membranes opposite
      the EC (day 0). On days 0, 1, 2, 4, 6, and 8, membranes were harvested (n = 3 per
      day), stained with Hoechst dye, and HA-SMCs were counted by fluorescence
      microscopy. Controls were HA-SMCs cultured alone. Comparisons were made by two
      way multivariate analysis of variance. RESULTS: During the entire 8-day period,
      there was significant induction of HA-SMC proliferation by both HSV-ECs (P =
      .0003) and HA-ECs (P = .0012). Maximal inductions were 88% +/- 11% for HSV-ECs (P
      = .0015) and 24% +/- 6% for HA-ECs (P = .0015). HSV-ECs exhibited a three- to
      ninefold greater induction than HA-ECs (P = .0003). CONCLUSION: HSV-ECs induce
      adjacent HA-SMC proliferation, possibly in a paracrine manner to a significantly
      greater extent than HA-ECs.

PMID- 9152911
TI  - CO2 digital subtraction angiography: potential complications and their
      prevention.

PMID- 9152912
TI  - CT angiography of Takayasu arteritis: comparison with conventional angiography.
AB  - PURPOSE: To compare computed tomography (CT) angiography with conventional
      angiography in the evaluation of the extent of disease in the aorta and its major
      branches in patients with Takayasu arteritis. MATERIALS AND METHODS: Both
      conventional (digital subtraction) and CT angiography were performed in 10
      patients with Takayasu arteritis. The luminal abnormalities were assessed with
      both conventional angiography and maximum intensity projection (MIP) CT
      angiography. Transverse images from CT angiography also were used to assess mural
      changes, which were not assessed with conventional angiography. RESULTS:
      Conventional angiography revealed 51 sites of luminal abnormalities. In five
      patients (50%), both conventional and MIP CT angiography depicted the same number
      of involved sites. At 36 of the 51 sites (71%), the estimation of luminal changes
      was the same for both modalities. In all patients, the transverse images provided
      additional mural findings in the aorta and its major branches. The integrated
      information provided by CT angiography, including MIP and transverse images,
      depicted more extensive disease than conventional angiography. CONCLUSION: CT
      angiography including MIP and transverse images has advantages over conventional
      angiography in the evaluation of disease extent by providing additional mural
      information in Takayasu arteritis.

PMID- 9152913
TI  - Transcolonic placement of a percutaneous nephrostomy tube: recognition and
      treatment.

PMID- 9152914
TI  - Iliofemoral deep venous thrombosis: safety and efficacy outcome during 5 years of
      catheter-directed thrombolytic therapy.
AB  - PURPOSE: To prospectively evaluate the angiographic and clinical results of using
      catheter-directed thrombolytic therapy for the treatment of acute iliofemoral
      deep venous thrombosis (IFDVT). MATERIALS AND METHODS: All consecutive patients
      with acute IFDVT referred for thrombolytic treatment from July 1990 to December
      1995 were included in this clinical data analysis. Infusions of urokinase were
      administered via a multisidehole infusion catheter. Angioplasty, stent placement,
      mechanical thrombectomy, and other procedures were often performed in conjunction
      with the thrombolytic procedure. RESULTS: Seventy-seven patients and 87 limbs
      were treated. The overall technical success rate was 79%, and was 86% for iliac
      veins and 63% for femoral veins. The primary and secondary patency rates at 1
      year were 63% and 78%, respectively, for the iliac veins, and 40% and 51%,
      respectively, for the femoral veins. Patients with malignant disease fared worse.
      Patients requiring stent placement appeared to have inferior outcomes. A previous
      history of DVT did not appear to affect the results. Bleeding requiring
      transfusion and hematomas were the major complications encountered. Pulmonary
      embolus was not a significant problem. Technical success rates were lower in
      patients who had had symptoms for more than 4 weeks compared to those who had a
      more recent onset of symptoms. CONCLUSION: Current data suggest that catheter
      directed thrombolytic therapy is safe and effective in achieving intermediate
      term venous Patency. The long-term clinical benefits of this procedure remain,
      however, to be established.

PMID- 9152915
TI  - Caval incorporation of the LGM Vena Tech filter: an experimental study.
AB  - PURPOSE: To analyze LGM Vena Tech filter incorporation and the rapidity of the
      process. MATERIALS AND METHODS: A filter was inserted into the infrarenal
      inferior vena cava (IVC) of 15 ewes assigned to one of three groups depending on
      the length of follow-up (2, 4, or 8 weeks). Radiologic data concerning IVC
      diameter and filter patency, stability, and incorporation were obtained before
      and after insertion and before euthanasia. Histopathologic analysis concerned
      wall thickness and smooth muscle cell area (SMCA) at three levels of the filter
      and at one point outside the filter. RESULTS: All filters remained patent during
      follow-up. Incorporation of struts was dependent on time (P = .006), level of the
      filter (P = .0001), and strut surface (P < .0001). Neointimal thickness increased
      during follow-up (P = .0002), being more marked in the midportion of the filter
      (P = .0037). Adventitial thinning was observed (P = .0001), corresponding to a
      significant decrease in SMCA (P < .0001) above the struts as a function of the
      length of the follow-up period (P = .0021). CONCLUSIONS: The LGM Vena Tech filter
      was well tolerated and is suitable for incorporation into the IVC wall of normal
      animals without risk of any deleterious reactions due to biological
      incompatibility.

PMID- 9152916
TI  - Percutaneous pulmonary thrombectomy.

PMID- 9152917
TI  - Distal retraction and inversion of the Simon nitinol filter during surgical
      venous procedures: report of two cases.

PMID- 9152918
TI  - Changes in tunneled catheter tip position when a patient is upright.
AB  - PURPOSE: To determine the relative changes in position of tunneled catheters from
      supine to upright patient position and factors affecting catheter tip migration.
      MATERIALS AND METHODS: One hundred forty-six different tunneled catheters were
      placed through the subclavian or jugular veins radiologically, and catheter
      positions were documented with use of cine radiography at the time of placement.
      Follow-up chest radiographs were obtained with the patient in the upright
      position within 48 hours after placement. Catheter tip positions were numbered
      from 1 to 8, with 1 representing the innominate/superior vena cava junction and
      8, the lower right atrium. Patient sex and weight, the site of catheter entry,
      and the size and type of catheter were correlated with the relative change in
      position on the follow-up chest radiogrpahs. RESULTS: There was a statistically
      significant (P < .0001) change in catheter position on the follow-up chest
      radiographs, with a mean difference of 1.5 catheter positions (usually mid-right
      atrium initially to low superior vena cava on follow-up). Catheter tip migration
      was greater for catheters in the subclavian veins, in females, and in obese
      patients. CONCLUSIONS: The catheter tip migrates significantly from the initial
      position at the time of placement as compared to when the patient assumes the
      upright position. This knowledge is important in achieving the desired final
      catheter position.

PMID- 9152919
TI  - Migration of central venous catheters: implications for initial catheter tip
      positioning.
AB  - PURPOSE: To evaluate the change in position of chest wall central venous access
      catheters (CVACs) after placement. Complication rates associated with catheter
      tip position were reviewed. PATIENTS AND METHODS: Fifty patients (36 women, 14
      men) with chest wall CVACs placed in the angiography suite were studied. Catheter
      migration was calculated as the difference between the carina-catheter tip
      measurements on immediate supine and upright postprocedure (within 24 hours)
      chest radiographs. Catheter-related complication data were gathered via telephone
      interview and review of the medical records. RESULTS: Peripheral catheter
      migration occurred in 49 of 50 patients (average, 3.2 cm +/- 1.8); central
      catheter migration occurred in one of 50 patients (3.9 cm). Catheter type was the
      only significant factor that affected the amount of migration; side of insertion
      or the patient's gender were not significant. Catheter malfunction and
      symptomatic upper extremity venous thrombosis rates tended to be lower in
      patients with right atrial versus superior vena cava catheters (18% vs 34%), but
      differences were not significant (P = .202). CONCLUSION: Catheter migration after
      chest wall CVAC placement is a common event. The catheter tip should be initially
      positioned approximately 3-4 cm more centrally than the desired final position.
      Further study is necessary of catheter-related complication rates relative to the
      final position of the catheter tip.

PMID- 9152920
TI  - Long-term results of transrenal ureteral occlusion with use of Gianturco coils
      and gelatin sponge pledgets.
AB  - PURPOSE: To evaluate transrenal ureteral occlusion with Gianturco coils and
      gelatin sponge pledgets. MATERIALS AND METHODS: The authors reviewed 34 ureteral
      occlusions in 22 patients during a 4-year period. The indications for this
      procedure included vesicovaginal fistula in 11 patients and urinary incontinence
      in three patients. All patients except one had a history of pelvic malignancy and
      previous radiation therapy. Pre-existing percutaneous nephrostomy tubes were in
      place in 20 ureters to be embolized. Distal ureteral occlusion was achieved by
      placement of Gianturco coils alone or in combination with gelatin sponge
      pledgets. A percutaneous nephrostomy catheter was then placed to provide
      permanent external diversion. Follow-up ranged from 2 weeks to 29 months (mean,
      6.2 months). RESULTS: Occlusion was technically successful in all embolized
      ureters. All patients experienced prompt resolution of symptoms as indicated by
      complete or near complete perineal dryness within 72 hours. Complications were
      limited to coil migration into the renal pelvis in two patients and nephrostomy
      catheter occlusion requiring replacement in another three patients. CONCLUSION:
      Ureteral occlusion with Gianturco coils and gelatin sponge is a safe and reliable
      method of achieving permanent supravesical urinary diversion in the management of
      chronic lower urinary tract fistulas.

PMID- 9152921
TI  - Percutaneous ureteral clipping: long-term results and complications.
AB  - PURPOSE: The authors present their experience with ureteral clipping in patients
      with urinary fistulas. MATERIALS AND METHODS: The authors retrospectively
      reviewed records from eight patients in whom 14 ureters were ligated with use of
      a percutaneously applied stainless steel clip as treatment for urinary fistulas.
      All patients were female and had undergone pelvic radiation for treatment of
      cervical carcinoma (n = 7) or endometrial carcinoma (n = 1). Permanent urinary
      diversion was via percutaneous nephrostomy, which required routine change, at
      which time recurrence of symptoms and ureteral leakage were determined. Duration
      of follow-up (patient survival) ranged from 2 weeks to 17 months (mean, 7.1
      months). RESULTS: All patients had significant improvement in their symptoms,
      with seven patients achieving complete perineal dryness. Two patients had
      recurrence of perineal symptoms due to nephrostomy tube blockage, which was
      successfully managed by means of interventional techniques. CONCLUSIONS: The
      authors believe that ureteral clipping is a safe and effective technique in the
      management of ureteral fistulas due to pelvic neoplasm and its treatment, despite
      the short life expectancy of these patients.

PMID- 9152922
TI  - Automated percutaneous lumbar discectomy: a prospective multi-institutional
      study.
AB  - PURPOSE: A prospective study in 10 independent hospitals from 1992 to 1994
      evaluated automated percutaneous lumbar discectomy (APLD) with a newly designed
      percutaneous instrument. MATERIALS AND METHODS: One thousand five hundred eighty
      two APLD procedures were performed in 1,525 patients with disc herniation or back
      pain. Mean follow-up after APLD was 18.3 months. Follow-up of at least 1 year was
      available in 1,474 patients. One thousand two hundred eighty-nine patients had
      sciatic pain and 185 had back pain only. Eight hundred twenty-two patients had
      symptoms for less than 2 years, 652 for more than 2 years. One thousand two
      hundred sixty-two patients were older than 60 years, 212 were younger than 60
      years. Nine hundred fifty patients had disc protrusion, and 357 had
      sequestration. Forty-eight patients had disc or longitudinal ligament
      calcification. Twenty-two had previous surgical discectomy. All discectomies were
      done with use of a straight needle with the patient in the lateral decubitus
      position. RESULTS: Success rate (measured by Hijikata's criteria) was 83% at 1
      year. Success was significantly greater for protrusion versus sequestration (86%
      vs 72%, P < .001); for back pain alone versus leg and back pain (89% vs 80%, P <
      .005); for duration of symptoms less than 2 years versus more than 2 years (85%
      vs 79%, P < .005); and for age younger than 60 years versus older than 60 years
      (84% vs 76%, P < .01). Among postsurgical patients, success rate was 77% (17 of
      22 patients). The only complication was discitis (0.06%, nine patients).
      Technical success at L5-S1 was 99% (795 of 800). CONCLUSION: APLD with Teng's
      instrument has excellent results. Indications may include back pain alone. A
      straight needle can be used at L5-S1 in most patients, with proper positioning.

PMID- 9152923
TI  - Combined percutaneous and endoscopic stent placement for an obstructed Roux limb
      after pancreaticojejunostomy for chronic pancreatitis.

PMID- 9152924
TI  - Bilomas developing after laparoscopic biliary surgery: percutaneous management
      with embolization of biliary leaks.

PMID- 9152925
TI  - Quality improvement guidelines for central venous access. The Standards of
      Practice Committee of the Society of Cardiovascular & Interventional Radiology.

PMID- 9152927
TI  - Renal artery origin from the superior mesenteric artery.

PMID- 9152926
TI  - Clinically relevant leakage in percutaneous colostomy.

PMID- 9152928
TI  - Use of a large-diameter coring needle to remove a foreign body.

PMID- 9152929
TI  - Prevalence and allele frequency estimation of bovine leukocyte adhesion
      deficiency (BLAD) in Holstein-Friesian cattle in Japan.
AB  - Blood samples from 796 Holstein dairy cows in 20 herds from 6 districts in Japan
      from June 1994 to August 1995 were examined to determine whether they were BLAD
      free, BLAD carriers, or BLAD-affected by use of DNA-polymerase chain reaction
      (PCR) analysis. The usage of semen of confirmed BLAD-carriers for artificial
      insemination in the Hokkaido district and two selected dairy farms was examined
      to estimate the gene frequency of BLAD carriers of sires. BLAD-carrier prevalence
      in 20 herds (796 cows, over 2.5 years old) ranged from 0 to 23.5%, and the mean
      BLAD-carrier prevalence was 8.1%. The BLAD-carrier prevalence in 10 herds (363
      cows) in which the occurrence of BLAD was not detected by the DNA-PCR test ranged
      from 0 to 12.5% with a mean of 5.4%. The BLAD-carrier prevalence in 10 herds (433
      cows) in which the occurrence of BLAD was confirmed by DNA-PCR analysis ranged
      from 2.6 to 23.5% with a mean of 10.8%, and these values were significantly (P <
      0.05) higher than those of dairy herds in which the occurrence of BLAD was not
      detected. The age distribution in BLAD carriers in these cows ranged from 2.5 to
      11 years. The mean gene frequencies of BLAD among 796 cows from 20 herds and 433
      cows from 10 herds in which the occurrence of BLAD was detected were 0.041 and
      0.054, respectively. The proportional usage of semen of BLAD carriers for
      artificial insemination in the Hokkaido district in 1992 was 12.6%, and its gene
      frequency was 0.058. On two selected farms in which higher BLAD-carrier rates
      were detected, the prevalences were 35.5% and 25.8%, and their gene frequencies
      were 0.177 and 0.129, respectively. The occurrence of BLAD-affected in Holstein
      dairy cattle was estimated to be 0.16-0.31% at birth in Japan without genetic
      control.

PMID- 9152930
TI  - Production of a monoclonal antibody (59.4) against canine lymphocyte surface
      antigen and its immunohistochemical application.
AB  - A monoclonal antibody was produced by immunizing BALB/c mice with freshly
      prepared canine thymocytes and peripheral blood leukocytes. The antibody,
      designated 59.4, was of the IgG1 subclass type and mainly reacted with
      lymphocytes. In single-color flow cytometric analysis, lymphocytes from the
      peripheral blood, thymus and spleen were graded into three categories according
      to their fluorescence intensity labeling by antibody 59.4: weakly, moderately and
      intensely positive cells. Two-color analysis revealed that a major population of
      CD8-positive cells were intensely labeled by antibody 59.4, but less than 50% of
      CD4-positive cells were moderately reacted with antibody 59.4.
      Immunohistochemically, thymocytes in the medulla showed moderately intense
      immunoreactivity to 59.4, but most lymphocytes in the cortex were negative in
      reaction. Immunostaining using antibody 59.4 demonstrated characteristic
      aggregations of 59.4-positive lymphocytes in the reticulum cell-free region of
      the thymic medulla. In the spleen, scattered lymphocytes in the outer layer of
      the marginal zone and in the red pulp were intensely labeled by antibody 59.4,
      while lymphocytes gathering in the mantle zone and periarterial lymphatic sheath
      (PALS) were moderately stained. Antibody 59.4 appears to recognize an antigen
      which is expressed by a more-differentiated T cell-lineage but not by immature T
      cells in the thymic cortex.

PMID- 9152931
TI  - Suppression of glucose absorption by some fractions extracted from Gymnema
      sylvestre leaves.
AB  - Extracts containing gymnemic acids, which were extracted from the leaves of
      Gymnema sylvestre (GS) as nine fractions, were evaluated for their effects on a
      high K(+)-induced contraction of guinea-pig ileal longitudinal muscles, on
      glucose transport mediated by the difference of glucose-evoked transmural
      potential difference (delta PD) in the inverted intestine of guinea-pig and rat,
      and on blood glucose in rat. Among nine fractions obtained by high performance
      liquid chromatography from the extract, f-2 and f-4 strongly suppressed the high
      K(+)-induced contraction of the ileal muscle, f-3 and f-5 did so moderately, and
      f-8 and f-9 did so weakly, whereas the other fractions did not affect it. The
      degree of suppression of high K(+)-induced contraction by f-2 at 74% was almost
      the same as that of f-4 at 67%, at concentrations of 0.1 mg/ml. The suppressed
      contraction by f-2 or f-4 was recovered by adding 5.5 mM pyruvate. The delta PD
      increased by 5.5 mM glucose in the inverted intestines of guinea-pig and rat were
      equally suppressed by 0.1 mg/ml of f-2 or f-4 to 40%. In a rat sucrose tolerance
      test, f-2 and f-4 suppressed the elevation of blood glucose level. Both f-2 and f
      4 suppressed the contraction of guinea-pig ileal longitudinal muscle, interfered
      with the increase in delta PD induced by glucose in the inverted intestines of
      guinea-pig and rat, and inhibited the elevation of blood glucose level. In
      conclusion, it is suggested that some of the extracts containing gymnemic acids
      from GS leaves suppress the elevation of blood glucose level by inhibiting
      glucose uptake in the intestine.

PMID- 9152932
TI  - Antigenic and plaque variations of serotype II feline infectious peritonitis
      coronaviruses.
AB  - Three feline coronavirus (FCoV) isolates KUK-H, M91-266, and M91-267 were
      examined to elucidate their biological and antigenic properties as well as
      disease potential in cats. Immune stainings of virus-infected cells by using FCoV
      type-specific monoclonal antibodies indicated that their antigenic specificity
      was serotype II. However, antigenic variations among these serotype II FCoVs were
      detected by neutralization assay with hyperimmune antisera against FCoVs and
      canine coronaviruses, and with experimentally infected cat sera; there were two
      subtypes in serotype II FCoVs. The isolates efficiently grew in fcwf-4 cell
      culture showing lytic CPE enough to form distinct plaques: when measured 48 hr
      after infection, plaque sizes of both M91-266 and M91-267 were approximately 1 mm
      in diameter, and a mixture of small (less than 1 mm in diameter) and large
      (approximately 3 mm in diameter) plaques were produced in the case of KUK-H.
      Strains KUK-H, M91-266 and M91-267 produced feline infectious peritonitis (FIP)
      in 50%, 67% and 89% of experimentally inoculated kittens, respectively.
      Furthermore, 80% of the kittens inoculated with the small plaque former of KUK-H
      developed FIP accompanied by more prominent clinical signs as well as
      pathological changes when compared with 28.6% of kittens inoculated with the
      large plaque former. These results suggest that serotype II FIPVs producing
      smaller size of plaques are more virulent than those producing larger size of
      plaques.

PMID- 9152933
TI  - Simple i.v. inoculation of HIV-1 to Thy/Liv SCID-hu mice induce reproducible HIV
      infection with narrowing of medulla in human thymic implant.
AB  - Human fetal thymus/liver engrafted SCID mice were constructed and studied for its
      susceptibility to HIVBRU infection by i.v. inoculation which seemed to represent
      an appropriate route of HIV infection in vivo. By the i.v. inoculation of HIV,
      the medulla in the engrafted thymus narrowed significantly when compared with
      that of the human thymic implant from virus-uninoculated mice. Further,
      immunohistochemical staining indicated the presence of HIV antigen predominantly
      in thymic epithelial cells in medulla of the engrafted thymus. Polymerase chain
      reaction (PCR) assays resulted in amplifications of HIV genome in the implanted
      grafts as well as in lymph nodes and PBMC. The virus infections to the implants
      were confirmed biologically by coculturing with PHA-stimulated human PBMC and the
      graft cells from the HIV-inoculated SCID-hu mice. Thus, the i.v. inoculation of
      HIV into Thy/Liv SCID-hu mice induce narrowing of medulla of the engrafted thymus
      and may become an efficient and useful tool for screening candidate anti-HIV
      agents.

PMID- 9152934
TI  - Epidemiological characterization of newly recognized rat parvovirus, "rat orphan
      parvovirus".
AB  - Newly recognized rat parvovirus (rat orphan parvovirus: ROPV) was examined for
      viral excretion and persistence in infected rats, and also for infectivity to
      mice and hamsters. The virus appeared to replicate mainly in lymphoid or
      hematopoietic tissues, and was detected in feces, urine and oropharynx of the
      infected rats at 1 to 4 weeks postinfection. The infective virus was also
      detected in peripheral leukocytes and various tissues at an acute phase of
      infection, and decreased in every tissue at 8 weeks postinfection. Viral DNA,
      however, was persistent in lymphoid tissues at least up to 24 weeks
      postinfection. When the virus was inoculated to mice and hamsters, no evidence of
      viral production and antibody response was demonstrated. ROPV is assumed to be a
      variant of the known rat parvovirus which resulted to alter cell tropism and
      persist in lymphoid or hematopoietic tissues, in order to escape from host immune
      system.

PMID- 9152935
TI  - Relationship between age-dependent changes of bovine neutrophil functions and
      their intracellular Ca2+ concentrations.
AB  - Neutrophil functions and intracellular Ca2+ concentrations ([Ca2+]i) were
      evaluated in 15 Holstein cattle divided into the following 3 groups: 5 neonatal
      calves less than 1 week old (group 1), 5 young calves 2 to 4 weeks old (group 2)
      and 5 cows 2 to 3 years old (group 3). The ability of neutrophils to phagocytose
      Candida albicans (C. albicans) was significantly higher (p < 0.05) in neonatal
      and young calves than in cows, whereas the phagocytosis by neutrophils of bovine
      IgG-coated yeasts (IgG-yeasts) was significantly lower (p < 0.05) in neonatal and
      young calves than that in cows. The killing activity by neutrophils of C.
      albicans in neonatal and young calves was significantly lower (p < 0.05) than
      that in cows. Luminol dependent chemiluminescent (LDCL) responses stimulated with
      opsonized zymosan (OPZ), heat-aggregated IgG (H-agg.IgG) and phorbol myristate
      acetate (PMA) were apparently lower in neonatal and young calves than in cows. No
      clearly different expressions of complement receptor type 3 (CR3) on neutrophils
      were observed among the 3 groups of cattle, although the values due to the
      binding of FITC-anti-bovine IgG to neutrophils in neonatal and young calves were
      lower than those in group 3. The OPZ-induced [Ca2+]i of neutrophils in neonatal
      and young calves were significantly higher (p < 0.05) than those in cows, but
      they were lower in neonatal and young calves when stimulated with H-agg.IgG.
      These results indicate that CR3- and FcR-mediated phagocytic and killing
      activities of neutrophils in neonatal and young calves are different from those
      in cows. These phenomena may be associated with age-dependent changes in [Ca2+]i.

PMID- 9152936
TI  - Selective survival of a thermostable direct hemolysin-producing Vibrio
      parahaemolyticus in the alimentary tract of a juvenile estuarine gastropod
      (Clithon retropictus).
AB  - Juvenile estuarine gastropods (Clithon retropictus), maintained in ultraviolet
      ray-irradiated recirculating artificial seawater with a salinity of 20/1000 at 28
      degrees C, preserved thermostable direct hemolysin (TDH)-producing strain D-3 of
      Vibrio parahaemolyticus at a level of 10(4)-10(5) colony forming units per gram
      (cfu/g) and TDH-non-producing strains N-18 and R-13 at a level of 10(1)-10(2)
      cfu/g in the alimentary tract for at least 21 days after ingestion. In adults,
      the numbers of the three strains decreased to a level of 10(0) cfu/g within 21
      days under the same conditions. This evidence supports our recent observations
      that TDH-producing strains increased to a high level in the summer months in the
      presence of high levels of TDH-non-producing strains in the alimentary tract of
      juvenile C. retropictus at estuaries in Japan.

PMID- 9152937
TI  - Characterization of porcine reproductive and respiratory syndrome virus
      hemagglutinin.
AB  - Porcine reproductive and respiratory syndrome virus hemagglutinin (HAin) was
      readily adsorbed on mouse erythrocytes at 4, 22, or 37 degrees C, but not on
      goose erythrocytes. The adsorbed HAin could not be eluted from the cells by
      resuspending in phosphate buffered saline, by incubating at 37 or 50 degrees C,
      or by incubating in the presence of neuraminidase. The hemagglutinating activity
      was not dependent on the pH and NaCl molarity tested. The receptor of mouse
      erythrocytes for the HAin was relatively stable to trypsin, neuraminidase, sodium
      deoxycholate (DOC), potassium periodate (KIO4), dithiothreitol (DTT), 2
      mercaptoethanol (2-ME) and formalin treatments. The HAin was inactivated by 2-ME
      and was gradually inactivated by pepsin, formalin and DTT, but not by beta
      glucosidase, trypsin, alpha-amylase, papain, phospholipase C, neuraminidase,
      KIO4, and ethylendiamine tetraacetic acid (EDTA) treatments. The HAin was stable
      at 37 degrees C or lower temperatures, but not at 56 degrees C or higher. The
      HAin was relatively resistant to ultraviolet irradiation and sonication. In the
      equilibrium centrifugation of the HAin preparation on a CsCl density gradient,
      the HAin activity showed a sharp peak at 1.17 g/cm2. In the SDS-PAGE analysis,
      the structural polypeptide of HAin in the peak fraction seems to be the
      nucleocapsid (N) polypeptide with molecular weight of 15 kDa.

PMID- 9152938
TI  - Maternal plasma estrone sulfate profile during pregnancy in the cow; comparison
      between singleton and twin pregnancies.
AB  - Peripheral plasma estrone sulfate (E(1)-S) concentrations were characterized
      throughout gestation in singleton and twin bearing cows by a direct
      radioimmunoassay method. Maternal plasma E1-S was detectable from around day 100
      and after that its concentration increased progressively to term in both
      singleton (n = 5) and twin bearing (n = 5) cows. Twin bearing cows had a
      significantly higher E1-S concentrations in some time from mid-gestation to term
      when compared to singleton cows. E1-S concentration in the twin bearing cows
      increased rapidly in the third trimester and peaked (16.7 ng/ml) on the day of
      calving. In the singleton cows the concentration increased gradually and peaked
      (7.1 ng/ml) about 10 days before calving and then subsequently decreased. Our
      results indicate that singleton and twin bearing cows show a disparate E1-S
      profile from mid-gestation to term.

PMID- 9152939
TI  - Bioavailability of ruminally protected sulfamethoxazole after oral administration
      in ruminating calves.
AB  - Bioavailabilities of oral rumen-protected and non-protected formulations of
      sulfamethoxazole (SMS) were compared in ruminating calves, since in vitro
      degradation of SMX in ruminal fluid was confirmed. The coated with a gastric-acid
      soluble polymer and uncoated formulations were administered to 3 calves through a
      catheter. Neither formulation could produce sufficient blood concentration of the
      drug, though the bioavailability of SMX for the coated formulation was higher
      than that for the uncoated formulation. It was suggested that the rumen-protected
      drug could improve the bioavailability by escaping from degradation in the rumen,
      but scarcely attain the effective levels in blood.

PMID- 9152940
TI  - Idiopathic renal hematuria in a dog; the usefulness of a method of partial
      occlusion of the renal artery.
AB  - Exploratory laparotomy was performed on a dog suspected of having idiopathic
      renal hematuria. Two catheters were inserted into the bilateral ureters, and
      hematuria from the left kidney was confirmed. The blood flow was occluded in the
      ventral and dorsal rami of the left renal artery in order to localize the site of
      hemorrhage. As hematuria disappeared when the dorsal ramus was occluded, the site
      of renal hematuria was localized to the area dominated by the dorsal ramus of the
      renal artery. As a result of ligating the dorsal ramus of the left renal artery
      in this dog, renal hematuria subsided, and the dog has shown a favorable course,
      to date, one year after surgery.

PMID- 9152941
TI  - Morphometry of abnormal peroxisomes induced by withdrawal of bezafibrate, a
      hypolipidemic drug in male rat hepatocytes.
AB  - Peroxisomes containing fibrillar structures were induced after 1 week withdrawal
      of bezafibrate, a peroxisome proliferator. In this report, the relation between
      the duration of bezafibrate treatment and the induction of abnormal peroxisomes
      in rat hepatocytes was studied morphometrically. The abnormal peroxisomes did not
      appear during 3 to 90 days of treatment with bezafibrate, but they appeared after
      1 week withdrawal of it. The number and frequency of abnormal peroxisomes were
      prominent in 3, 7, and 14 days of treatment followed by 1 week of withdrawal of
      bezafibrate. It was evident that the frequency of abnormal peroxisomes decreased
      with 30-90 days administration of bezafibrate. This means that long-term (30-90
      days) treatment with bezafibrate suppresses the induction of abnormal
      peroxisomes.

PMID- 9152942
TI  - Detection of bovine leukemia viruses (BLV) in mammary tissues of BLV antibody
      positive cows affected by subclinical mastitis.
AB  - The mammary tissues of 6 cows with bovine leukemia virus (BLV) antibody and
      subclinical mastitis were investigated histopathologically, and their organ
      cultures were ultrastructurally observed. Numerous BLV particles, 110 to 120 nm
      in diameter, were seen around lymphocytes, which had infiltrated into mammary
      alveoli and showed blastogenesis under culture. Particles budding from the cell
      membrane were also found.

PMID- 9152943
TI  - Magnetic resonance imaging of rat head with a high-strength (4.7 T) magnetic
      field.
AB  - This study was designed to seek the appropriate scanning parameters for T1 and T2
      weighted images of rat head by use of a high (4.7 T) magnetic field strength
      magnetic resonance imaging unit. The optimum values of variables for T1 weighted
      images were considered to be a time of repetition of 1,000 msec, and for T2
      weighted images, 8 echoes. When the sagittal images of a healthy rat head were
      scanned using these optimum values, the cerebrum, cerebellum, olfactory bulb,
      pituitary gland, pineal gland, spinal cord, tongue, nasopharynx, nasal conchae,
      vermis and cerebrospinal fluid were clearly observed in either T1 or T2 weighted
      images. Moreover, a primary brain tumor induced by ethylnitrosourea was depicted
      as a high signal intensity mass in T2 and contrast-enhanced T1 weighted images.

PMID- 9152944
TI  - Chemical restraint of African lions (Panthera leo) with medetomidine-ketamine.
AB  - Effects of a combination of medetomidine-ketamine as a chemical restraint and
      antagonistic effects of atipamezole on this combination were investigated in 5
      lions. The medetomidine (47.6-58.4 micrograms/kg) and ketamine (1.9-5.7 mg/kg)
      combination provided complete immobilization with good analgesia and muscle
      relaxation in 4 lions, while one lioness was poorly sedated by medetomidine, and
      additional injections of medetomidine and ketamine were required. The duration of
      anesthesia seemed to be much longer than one hour in 4 of the lions. Atipamezole,
      at four times the preceding dose of medetomidine, provided a smooth recovery and
      animals were able to stand up 17-61 min after its injection. Side effects were
      limited to vomiting after walking in 3 of 5 lions.

PMID- 9152945
TI  - International differences in epidemiology of lung adenocarcinoma.
AB  - In Europe, the squamous cell carcinoma is the most frequent non-small cell lung
      cancer (NSCLC) subtype and until now, no increase in incidence of lung
      adenocarcinoma (ADC) has been described (except in the Netherlands), in contrast
      to North America where ADC predominates. Our aim was to compare the percentage of
      ADC in Montreal (MTL), Canada, with that in Strasbourg (STBG), France. We
      prospectively identified patients with NSCLC in MTL and in STBG over an 8-month
      period and described the distribution of NSCLC by sex, age, subtype and smoking
      history. A total of 172 patients in MTL and 166 in STBG were identified. The
      male/female ratio was significantly different in STBG (12:1) and in MTL (2:1).
      The percentage of ADC was significantly higher in MTL (40%) than in STBG (30%).
      This difference is partly due to the higher number of women with NSCLC in
      Montreal combined with the predominance of ADC in women. The proportion of ADC
      decreased with age in STBG, but was similar in each age category in MTL. In STBG,
      most women with NSCLC had never smoked (69%), in contrast to MTL where only 16%
      of women had never smoked. In conclusion, ADC is more frequent in MTL than in
      STBG. This is partly due to the higher number of women with NSCLC in MTL combined
      with the predominance of ADC in women. The greatest proportion of ADC subtype in
      the youngest cohorts of men in STBG suggests that ADC may be on the rise in this
      city.

PMID- 9152946
TI  - Meta-analysis of the potential relationship between exposure to environmental
      tobacco smoke and lung cancer in nonsmoking Chinese women.
AB  - A meta-analysis of six case-control studies on the relationship between reported
      exposure to environmental tobacco smoke (ETS) and lung cancer in nonsmoking
      Chinese women was performed, using the fixed-effect model. A total of 767 cases
      and 1193 controls from Shanghai, Guangzhou, Shenyang, Harbin, Xuanwei, and Hong
      Kong were reported in five of these six studies. (One study did not provide a
      clear description of the number of cases and controls). The Fleiss method was
      used to calculate the overall odds ratio (OR), the test of average degree of
      association (chi 2 assoc), the degree of homogeneity (chi 2 homog) and the 95%
      confidence interval (CI). The overall OR of lung cancer risk in nonsmoking
      Chinese women from exposure to ETS is 0.91 (95% CI, 0.75-1.10, chi 2homog = 4.51,
      P > 0.25). No statistically significant relationship was found between either the
      amount (cigarettes/day) or the duration (in years) of exposure to ETS and lung
      cancer. Bias and confounding factors are briefly discussed.

PMID- 9152947
TI  - Preferential histiotypic expression of CD44-isoforms in human lung cancer.
AB  - The CD44 transmembrane glycoprotein is expressed in most adult tissues and in the
      majority of neoplasias. Due to alternative splicing, this cell adhesion molecule
      exists in multiple isoforms some of which have been associated with specific
      types of tumours as well as with increased tumour metastasis. In this study, we
      have looked at the level and type of CD44 expression in lung cancer which
      represents a histologically heterogenous form of cancer composed of small cell
      lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC), the latter
      subgroup comprising adenocarcinoma (ADC), bronchio-alveolar carcinoma (BAC),
      large cell carcinoma (LCC), and squamous cell carcinoma (SCC). We analysed 20
      lung cancer cell lines and 64 primary tumours by RT-PCR and immunohistochemical
      detection of the CD44 standard and variant protein isoforms. Our results suggest
      that (i) CD44 is expressed in all histologically distinct subsets of lung cancer
      with a tendency SCC > BAC > ADC > LCC > SCLC, (ii) expression of the CD44
      isoforms v5, v7, v8, and, most notably that of CD44 exon v6, strongly correlates
      with tumours of squamous cell and bronchio-alveolar carcinoma origin, tumours
      which commonly exhibit a comparatively low metastasizing potential, and (iii) the
      expression of CD44 isoforms is independent from the tumour size and lymph node
      status at surgery, the proliferative status of the tumour cell population (Ki67
      antigen expression) and the histopathological grading (G1 to G3). Only non
      differentiated tumours (G4), which were restricted to SCLC and LCC samples
      revealed markedly reduced CD44 standard and isoform antigen. In conclusion, our
      data point to a clear histiotype-related pattern of CD44 variant expression
      preferentially that of CD44v6 in SCC and BAC.

PMID- 9152948
TI  - Clinical and flow cytometric prognostic factors in surgically treated squamous
      cell lung cancer.
AB  - A five-year follow-up study of prognostic factors in 207 patients with squamous
      cell lung cancer (SqLC) radically treated with surgery was investigated. Cellular
      prognostic indicators for survival times, such as percentage of cells in the S
      phase (S-phase fraction, SPF), proliferative index (PI, number of cells in S +
      G2/M phases) and DNA ploidy, in addition to well known clinical factors were
      studied. Patients with aneuploid tumours had significantly shorter survival
      period (P < 0.05) than patients with diploid tumours. However, proliferative rate
      of the tumours had no influence on patients' survival. Cox multivariate analysis
      showed that metastases to the neighbouring lymph nodes, tumour diameter > 5 cm
      and DNA aneuploidy of the tumour cells were the negative factors which affected
      patients survival. DNA ploidy did not depend on the clinical stage of the
      tumours.

PMID- 9152949
TI  - Thoracoscopic evaluation of histologically/cytologically proven or suspected lung
      cancer: a VATS exploration.
AB  - To evaluate the diagnostic value of video-assisted thoracic surgery (VATS), VATS
      exploration was performed in 135 patients with histologically/cytologically
      proven or suspected lung cancer. In 31 patients with pulmonary nodules suspected
      to be lung cancer, VATS exploration was intended to determine their histology by
      wedge resection. A histological diagnosis was made in all of the patients: 12
      lung cancers (38.7%), 12 inflammatory granulomas (38.7%), four hamartomas
      (12.9%), and three others. VATS exploration (staging) was performed in 116
      surgical candidates with documented lung cancer, including the 12 patients
      diagnosed by VATS wedge resection. Inoperable factors were demonstrated by this
      procedure in five patients (4.3%): malignant effusion without dissemination in
      three, malignant effusion with extensive dissemination in one, and extensive
      dissemination without effusion in one. Furthermore, N2 nodal metastasis at
      Botallo's ligament was demonstrated by this procedure in two patients, which met
      the eligibility criteria for a clinical study. Although the documented number of
      patients was relatively small, VATS exploration obviated the need for painful
      thoracotomy, selecting better treatment and for evaluating eligibility criteria
      for prospective clinical trials. The results suggest that this procedure is
      useful in candidates for lung cancer surgery.

PMID- 9152951
TI  - Defining the roles of high dose rate endobronchial brachytherapy and laser
      resection for recurrent bronchial malignancy.
AB  - Endobronchial therapy is commonly used in the palliative management of malignant
      disease, but the optimal combinations of treatment modalities (laser,
      brachytherapy, external beam radiotherapy) have not been defined. We have
      undertaken a prospective analysis of symptom response, duration of response, and
      prognostic factors for 117 patients treated with brachytherapy at a single
      centre, to identify hypotheses suitable for prospective randomised studies. All
      but one patient had received previous treatment. The percentage of patients with
      scores of 0 or 1 (none or mild) for each symptom pre-treatment and at 3 months
      were as follows: cough 62% to 77% (43% improving by at least one grade, N.S.);
      dyspnoea 32% to 56% (50% improvement by at least one grade, P = 0.0063);
      haemoptysis 78% to 97%; performance status 65% to 84% (54% by at least one grade,
      P = 0.0417). An actuarial risk of fatal haemoptysis at 2 years of 20% was
      associated with prior laser resection (P = 0.048). Death before 2 months was
      associated with dyspnoea scores of 3 or 4. Suggestions for randomised studies are
      made to address some of the uncertainties revealed by the analysis.

PMID- 9152950
TI  - Usefulness of longitudinal evaluation of Cyfra 21-1 variations in advanced lung
      cancer monitoring.
AB  - To investigate the usefulness of Cyfra 21-1 as an indicator of therapy
      effectiveness and prognosis in advanced primary lung cancer, sixty-three patients
      were selected on the basis of a high Cyfra 21-1 serum level (> 3.3 ng/ml) at the
      time of diagnosis. Serial assays of Cyfra 21-1 were performed during the first
      three courses of chemotherapy among 63 patients. The serial-values were analysed
      according to response to treatment and overall survival. After three courses of
      chemotherapy, a 70% reduction under the initial marker's value or a return to
      normal was observed for 36 patients. Twenty-two (61%) of these patients presented
      an objective response to therapy, making Cyfra 21-1 a moderate indicator in terms
      of positive predictive value (PPV). However, a significant decrease of Cyfra 21-1
      was observed in 88% (sensitivity) of the 25 objective responders. Cyfra 21-1
      changes after one course of chemotherapy (61 patients) were not sufficient to
      predict the future response after three courses (sensitivity 52%, specificity
      56%, PPV 45%). Among 30 clinical or radiological relapses, a 10% increase or a
      return upper reference limit in Cyfra 21-1 level was observed in 18 cases
      (sensitivity 60%, specificity 100%, PPV 100%). Survival data were available for
      61 patients. No significant statistical difference (P > 0.05) was found between
      survival curves depending on a significant decrease of Cyfra 21-1 after the first
      course of chemotherapy. We can conclude that the only interest of serial Cyfra 21
      1 assays may be the detection of relapse, where one observes a significant
      decrease of the marker correlated with an objective response to first treatment.

PMID- 9152952
TI  - Intrapericardial cisplatin for the management of patients with large malignant
      pericardial effusion in the course of the lung cancer.
AB  - Patients with cardiac tamponade or large malignant pericardial effusion, who
      survived longer than 30 days after withdrawal of catheter from the pericardial
      space, entered the study. Main goal of investigations was: evaluation of the
      effectiveness and side-effects of intrapericardial administration of cisplatin in
      cases with malignant pericardial effusion (MPE) and cardiac tamponade or large
      pericardial effusion in a course of the lung cancer. Sixteen patients (four women
      and 12 men), mean age 53 years, median age 57 years, range 27-70 years, entered
      this retrospective study. After pericardiocentesis and insertion of a
      polyurethane catheter, pericardial fluid was drained. Malignant etiology of
      pericardial fluid was confirmed by cytological examination and/or by
      echocardiography. The diagnosis of malignancy was based upon histological
      examination of samples obtained from primary tumor. After confirmation of MPE
      cisplatin (10 mg in 20 ml normal saline) was instilled over 5 min during 1-5
      consecutive days (maximal total cisplatin dose in single course: 50 mg) directly
      into pericardial space. If a large pericardial fluid reoccurred the courses with
      intrapericardial administration of cisplatin were repeated. Treatment was
      considered successful if the patient with malignant effusion survived 30 days
      without recurrence of symptoms of large pericardial effusion and no other
      interventions directed to the pericardium were required. In 14 (87.5%) cases
      malignant pericardial effusion was confirmed by cytological analysis of
      pericardial fluid. In two cases echocardiography confirmed metastatic tumors to
      the pericardium. Positive effect of intrapericardial treatment with cisplatin was
      achieved in 15 cases (93.75%). Mean survival period in the whole group was 6.59
      months (+/-6.2 months), median survival period was 3.7 months, range 2-24.1
      months. There were no complications related to the pericardiocentesis. Transient
      atrial fibrillation was detected in three patients (18.8%). Mild nausea occurred
      in one case. No hypotension and retrosternal pain were observed. Cisplatin
      administered directly into pericardial space (CAP) seems to be effective and
      safe. No sclerosis of the pericardial space was observed after CAP.

PMID- 9152953
TI  - Inflammatory pulmonary pseudotumor in an adolescent.
AB  - Primary pulmonary neoplasia in youth is uncommon, but malignant entities of
      varied histology predominate. A case of primary inflammatory pulmonary
      pseudotumor of the lung in an adolescent with a huge lung mass is presented. This
      finding represents the preponderance of benign lung neoplasms found in children
      and adolescents and must be considered when only inflammatory cells are recovered
      at bronchoscopy.

PMID- 9152954
TI  - Measurement of serum p53 protein in patients with small cell lung cancer and
      results of its clinicopathological evaluation.
AB  - Serum p53 protein levels were measured in 36 patients with small cell lung cancer
      (SCLC) and 35 patients with benign lung diseases in order to evaluate the
      relationship of these levels to clinicopathological features of SCLC. Serum
      levels of p53 protein were measured by an enzyme-linked immunosorbent assay, p53
      protein level was 23.92 +/- 6.78 pg/ml in patients with SCLC, and similar to that
      (17.47 +/- 2.86 pg/ml) in patients with benign lung diseases. By the clinical
      stage of SCLC, the mean level of p53 protein was 16.68 +/- 4.62 pg/ml in 21
      patients with limited disease, and lower than that in 15 patients with extensive
      disease (34.05 +/- 14.84 pg/ml) (P = 0.23). The levels of p53 protein were not
      correlated with age, smoking index, or presence of cancer history for patients
      with SCLC. However, immunohistochemical examination disclosed a mild correlation
      between the expression of p53 protein by SCLC tumor and p53 protein serum level
      (r = 0.45, P = 0.02). Two patients with SCLC had an elevated serum level of p53
      protein (> 2 S.D. above the mean for benign lung diseases). However, measurement
      of p53 protein serum level was not found to be clinically useful for detection of
      SCLC.

PMID- 9152956
TI  - Report on the 4th Central European Lung Cancer Conference Gdansk, Poland, 26-29
      September 1996.

PMID- 9152955
TI  - 5th I.A.S.L.C. Lung Tumor Biology Workshop, August 13-17, 1996, Ermatingen,
      Switzerland.

PMID- 9152957
TI  - Postnatal development of dopamine D1-like and D2-like receptors in the rat
      kidney: a radioligand binding study.
AB  - Dopamine exerts important natriuretic and renal haemodynamic changes mediated
      through the interaction with dopamine D1-like and D2-like receptors. Dopamine
      mediated natriuresis and renal vascular effects are less in younger than in older
      animals. The pharmacological profile and the density of dopamine D1-like and D2
      like receptors were assessed in the kidney of rats ranging from 2 to 90 days of
      age by using radioligand binding assay techniques. [3H]SCH 23390 was used as
      ligand of dopamine D1-like receptors. [3H]Spiperone was used as a ligand of
      dopamine D2-like receptors. The dissociation constant (Kd) value of [3H]SCH 23390
      binding was slightly decreased from the 21st day of age in comparison with
      animals of 2 and 7 days of age. The maximum density (Bmax) of [3H]SCH 23390
      binding sites increased progressively until the 21st day of age and then
      plateauned. A similar trend was found for [3H]Spiperone binding sites. In
      [3H]Spiperone binding experiments, the Kd value was remarkably decreased from the
      21st to the 90th day of life. Bmax value of [3H]Spiperone binding sites were
      similar in rats of 2 and 7 days of age and subsequently increased to values
      similar to those found in adult rats from the 21st day of life. The
      pharmacological profile of [3H]SCH 23390 and [3H]Spiperone was similar in rats of
      the different ages investigated. These findings suggest that renal dopamine D1
      like and D2-like receptors undergo maturational changes in the first 3 weeks
      after birth and then are stabilized at the adult levels. The possibility that the
      increased expression of renal dopamine receptors postnatally may be linked with
      the gradual appearance of dopamine-mediated renal responses after birth is
      discussed.

PMID- 9152958
TI  - Effects of vinconate on age-related alterations in [3H]MK-801, [3H]glycine,
      sodium-dependent D-[3H]aspartate, [3H]FK-506 and [3H]PN200-110 binding in rats.
AB  - We investigated the effects of age and (+/-)-methyl-3-ethyl-2,3,3a,4-tetrahydro-1
      H-in-dolo[3,2,1-de] [1,5] naphthyridine-6-carboxylate hydrochloride (vinconate),
      an indolonaphthyridine derivative, on calcium channels, neurotransmitter receptor
      systems and immunophilin in Fischer rat brain using quantitative receptor
      autoradiography. [3H]MK-801, [3H]glycine, sodium-dependent D-[3H]aspartate,
      [3H]FK-506 and [3H]PN200-110 were used to label N-methyl-D-aspartate (NMDA)
      receptors, glycine receptors, excitatory amino acid transport sites, FK-506
      binding proteins (FKBP) and voltage-dependent L-type calcium channels,
      respectively. [3H]Glycine and sodium-dependent D-[3H]aspartate binding
      significantly decreased in the frontal cortex, parietal cortex, striatum, nucleus
      accumbens, hippocampus, thalamus, substantia nigra and cerebellum of 24 month old
      rats in comparison with 6 month old animals. In contrast, [3H]MK-801, [3H]FK-506
      and [3H]PN200-110 binding showed no significant changes in the brain of 24 month
      old rats. Intraperitoneal chronic treatment with vinconate (10 and 30 mg/kg, once
      a day for 4 weeks) dose-dependently ameliorated the significant reduction in
      [3H]glycine and sodium-dependent D-[3H]aspartate binding in the brain of 24 month
      old rats. These results demonstrate that glycine receptors and excitatory amino
      acid transport sites are more susceptible to aging processes than NMDA receptors,
      immunophilin and voltage-dependent L-type calcium channels. Furthermore, our
      findings suggest that vinconate may have a beneficial effect on age-related
      changes in glycine receptors and excitatory amino acid transport sites.

PMID- 9152959
TI  - Effect of age on the vasodilatory action of elastin peptides.
AB  - We have recently shown, on young adult rat aorta rings, that elastin peptides
      induce a dose and endothelium-dependent vasodilation mediated by the 67 kDa
      subunit of the high affinity elastin-laminin receptor and, at least in part, by
      EDRF (NO). Here we have studied the effects of elastin peptides at circulating
      concentrations and below, on noradrenaline-contracted rat aortic rings, as a
      function of age. First, we have observed that, unlike 2-month-old (2M), 4-6-month
      old (4M) and 12-month-old (12M) rat aorta rings, 30-month-old (30M) rat aorta
      rings were unable to maintain their contraction in long lasting experiments.
      Secondly, elastin peptides at physiological circulating concentrations (10(-6)
      10(-3) mg/ml) induce a dose-dependent vasodilation on 4M rings. By contrast, only
      higher elastin peptide concentrations (10(-3) mg/ml) were effective on 12M rings,
      whereas rings from both younger (2M) and older animals (30M) did not respond to
      elastin peptides. Finally, using lactose and laminin as inhibitors, we have
      demonstrated that elastin peptide-induced vasodilation on 4M and 12M rings is
      mediated by the 67 kDa subunit of the elastin-laminin receptor. These experiments
      suggest that the functional availability of the 67 kDa subunit of the elastin
      laminin receptor changes with age. It could be hypothesized that in young animals
      (0-2M) the reusable shuttle role recently demonstrated for the 67 kDa receptor
      subunit during elastic fiber formation leads to a major decrease in its
      availability for signal transduction. On the contrary, in adult animals. (4-12M),
      when developmental elastogenesis is completed, this subunit is essential for
      extracellular signal transduction. Inefficiency of this receptor in old animals
      (30M) can be attributed to its uncoupling from its transduction pathway, as
      previously shown on human cells. Finally, the age-dependent variations of
      circulating elastin peptide concentration and elastin-laminin receptor
      responsiveness to elastin peptides are two independent parameters which could
      influence the vascular tension regulation.

PMID- 9152960
TI  - Age and temperature related changes in behavioral and physiological performance
      in the Peromyscus leucopus mouse.
AB  - Age-related and ambient temperature-related changes in motor activity, body
      temperature, body weight (b.w.), and food consumption were studied in the long
      lived Peromyscus leucopus mouse at environmental temperatures of 29 and 21
      degrees C. Major changes in physiological performance were observed between the
      young (6 months) and old (60-72 month) age groups. The number of daily activity
      episodes, and total activity output was significantly lower in old mice. Maximum,
      average and minimum daily body temperature was lower in the old mice and a
      significant ambient temperature-by-age interaction was found. Maximum, minimum,
      and average daily b.w. was higher in old mice. Motor activity was evenly
      distributed over the active (night) phase in young mice but in old mice activity
      was significantly greater in the late night partition of the active cycle than in
      the early night partition. Both groups were significantly more active at night
      than during the day. Most of the food consumption in both groups occurred at
      night, but young mice consumed significantly more during the late night partition
      than the early night partition, and the consumption rates for old mice were not
      significantly different between early and late night partitions. The percentage
      of activity episodes involved with food consumption in both groups was
      significantly higher during the night partition, but the percentage during the
      early night partition was significantly higher in old mice than in young mice.
      Significant episodes of circadian torpor occurred in a high percentage of old
      mice at 06:00, on consecutive days, at both environmental temperatures, but young
      mice expressed no evidence of torpor.

PMID- 9152961
TI  - Nucleosomal organization of the rat liver satellite DNA-containing chromatin
      during aging.
AB  - Nucleosomal organization of the satellite DNA-containing chromatin of the liver
      of young (18 +/- 2 weeks) and old (100 +/- 5 weeks) rats was examined by
      nucleases and satellite I DNA probe. The satellite DNA-containing chromatin
      exhibits lower accessibility to endogenous endonucleases in old rats. The
      nucleosomal repeat length of this chromatin as investigated from digestion with
      endogenous endonucleases and MNase differs remarkably from bulk chromatin, though
      it does not alter with age. However, age-dependent loss of satellite DNA is
      apparent from hybridization results. Furthermore, DNase I analysis of the
      satellite DNA-containing chromatin at nucleosomal level reveals a relatively
      loose organization in young rats than old ones. It also shows an altered 10 bp
      periodicity as compared to bulk chromatin in both ages. These findings establish
      organizational differences between rat liver bulk and satellite DNA-containing
      chromatin. They further show that repeat length and altered 10 bp periodicity are
      similar in young and old, but accessibility to nucleases declines with age.

PMID- 9152962
TI  - Role of glutathione conjugation in protection of weanling rat liver against
      acetaminophen-induced hepatotoxicity.
AB  - The rate of glutathione (GSH) conjugate formation to acetaminophen (APAP) in
      livers of weanling and adult rats treated with a single i.p. dose of APAP was
      compared. HPLC analysis of cytosolic fractions revealed that rate of conjugation
      in weanling rat is 24-times greater than that of adults. Increased rate of GSH
      conjugation was independent of of the age-related difference observed in liver
      GSH content. The normal level of liver GSH in weanling rat was 57% of adult
      level. APAP treatment depleted GSH more significantly in weanling rats as
      compared to that in adults. N-acetylcystein (NAC) alone had little influence on
      liver GSH levels. However it was successful in reducing GSH depletion in tissues
      of growing rats. A 32% repletion in hepatic GSH level in NAC-treated weanling
      rats was associated with a further 13-fold increase in the rate of GSH conjugate
      formation. These data together with histopathological results, clearly showed
      that the inducible GSH system in weanling rat liver act as a safe guard against
      APAP toxicity. A surge in the rate of APAP-GSH conjugation in growing liver may
      function in compensation of other detoxification pathways which are saturated
      more readily at this age.

PMID- 9152963
TI  - Ageing promotes the increase of early glycation Amadori product as assessed by
      epsilon-N-(2-furoylmethyl)-L-lysine (furosine) levels in rodent skin collagen.
      The relationship to dietary restriction and glycoxidation.
AB  - Glucose has been implicated in the aging process by its ability to react
      nonenzymatically with long-lived proteins like collagen to produce advanced
      glycosylated end-products (AGEs). In the initial phase of this reaction, referred
      to as glycation, glucose reacts with the free amino group of proteins resulting
      in Schiff base formation followed by rearrangement to an Amadori product. Since
      the Amadori product is transient due to its conversion to other products as well
      as its reversibility to the initial products, glycation as an age-related marker
      in collagen has questionable significance. In human studies, glycation of
      collagen has been found to increase modestly with age. In rodent studies, results
      are conflicting due to differences in methodology. Thus, it has been concluded
      that collagen glycation either does not vary or increases modestly with age. In
      the present study, a C8 HPLC column was used to measure Amadori product formation
      as the acid-hydrolyzed breakdown product furosine in the skin of rats and mice.
      Surprisingly, levels were found to increase at a rapid rate during aging of
      rodents. Impurity of the furosine peak from the use of crude acid-hydrolyzed skin
      samples was ruled-out because reductive properties and spectroscopic profiles
      matched those previously described for furosine. In the present study, glycemia
      was found important in furosine formation as shown by the glycation lowering
      effects of dietary restriction on collagen. Decreased collagen turnover probably
      plays a substantial role in explaining the age-related increase in furosine
      levels in rodent skin collagen.

PMID- 9152964
TI  - Effects of transforming growth factor-beta 1 and interleukin-1 alpha on matrix
      synthesis in osteoarthritic cartilage of the temporo-mandibular joint in aged
      mice.
AB  - Osteoarthritic lesions were observed in the mandibular condyle cartilage of mice
      aged 7 months and older. These lesions appeared as fibrillations along the
      articular surface and were accompanied by reduced extracellular matrix synthesis
      and chondrocyte proliferation. Explants of mandibular condyle cartilage were
      cultured in serum-free BGJb medium supplemented with ascorbic acid (300
      micrograms/ml), penicillin (100 U/ml) and streptomycin (100 micrograms/ml) for up
      to 72 h. Cultures were further supplemented with either hTGF-beta 1 (0.1-5.0
      ng/ml) or human IL-1 alpha (40 U/ml). [3H]thymidine (2 microCi/ml) and [35S]SO4
      (10 microCi/ml) were added to the culture medium for the last 24 h of culture and
      incorporation into DNA and sulfated proteoglycans, respectively, studied. The
      results indicated that protein and DNA contents, [3H]thymidine and [35S]SO4
      incorporation, as well as the specific activity of alkaline phosphatase, were
      increased by TGF-beta 1. Addition of 1.0 or 5.0 ng/ml hTGF-beta 1 to the cultures
      for 48 h, had the most stimulatory effect on matrix synthesis and cell
      proliferation, whereas 0.1 ng/ml hTGF-beta 1 appeared to be inhibitory when
      compared to controls. Increased [35S]SO4 labeling of chondrocyte clusters was
      observed by autoradiography in tissue sections from cultures treated with TGF
      beta 1 (1.0 and 5.0 ng/ml). In contrast, IL-1 alpha exerted inhibitory effects on
      cell proliferation and matrix synthesis. However, it induced the activity of acid
      phosphatase in these cultures. The results of the present study show that IL-1
      alpha had catabolic effect on his tissue, while TGF-beta 1 enhanced proliferation
      and induced synthetic activity of the cartilage cells. Such action by TGF-beta
      suggests the existance of a possible repair process in osteoarthritic cartilage
      of the temporo-mandibular joint of aged mice.

PMID- 9152965
TI  - Effects of age and gender on the AII-induced stimulation of prolactin release and
      inositol phosphate accumulation in rat anterior pituitary cells in vitro.
AB  - The stimulatory effects of Angiotensin II (AII) on prolactin secretion and
      inositol phosphate accumulation were examined in dispersed anterior pituitary
      cells collected from young (3-4 month), mature (7-8 month) and old (18-20 month)
      male and female rats. Physiological doses of AII (0.01-10 nM) stimulated
      prolactin release from cells collected from mature female rats only. This effect
      was antagonized by pretreatment with Saralasin, an AII receptor antagonist.
      Significant accumulation of the inositol phosphates was observed in cells
      obtained from the mature, female donors and this increase preceded the prolactin
      response. Although there was a small increase in total inositol phosphate
      accumulation in cells obtained from the old female rats, this was transient and
      did not coincide with a similar increase in prolactin release. These results
      indicate that pituitary sensitivity to AII stimulation is related to the age and
      the gender of the donor animal. The physiological role of pituitary AII needs to
      be examined in sexually mature female animals.

PMID- 9152966
TI  - Aging of the recipients but not of the bone marrow donors enhances autoimmunity
      in syngeneic radiation chimeras.
AB  - Young and old mice have been lethally irradiated and injected with syngeneic bone
      marrow cells from young or old donors to investigate whether self reactivity in
      old mice results from age-related damage of the radioresistant stromal cells
      and/or of the bone marrow hematopoietic cells. Thymus and spleen cell
      repopulations and mitotic responses at 3 months after irradiation are lower in
      old than in young recipients, suggesting age-related accumulation of stromal cell
      damage in the thymus as well as in other central and peripheral lymphoid tissues.
      The same efficiency of bone marrow cells from young and old donors to repopulate
      the thymus and spleen in recipients of equal age rules out the detrimental
      effects of aging on stem cells as well as T and B cell precursors. The serum
      concentration of auto-antibody and glomerular lesions at 3 and 9 months after
      irradiation were more pronounced in old than in young recipients and displayed no
      difference in recipients of equal age, regardless of the age of the bone marrow
      cell donors. These findings support the possibility that age-related damage of
      stromal cells induces disregulation of the immune system leading to autoimmune
      phenomena.

PMID- 9152967
TI  - Developmental dynamics of endothelial and neurogenic control of canine thoracic
      aorta.
AB  - The purpose of the study was to confront the range of endothelial relaxation and
      neurogenic contraction of the thoracic aorta in fetuses (1 week before birth),
      puppies (1, 2, 4 and 6 weeks old), and in adult dogs. Isometric tension of aortic
      rings was monitored in organ bath. Acetylcholine-induced dose-dependent
      relaxation of aortic rings precontracted by phenylephrine was pronounced already
      in fetuses and puppies and significantly larger than in adults. Indomethacin, a
      cyclooxygenase inhibitor, did not affect the magnitude of aortic relaxation to
      acetylcholine. Transmural nerve stimulation induced but very slight contractions
      of the thoracic aorta in fetuses, while in puppies the extent of contractions was
      increasing with increasing age, reaching its maximum in adults. Contractile
      responses of aortic rings induced by KCl were fully detectable in fetuses and
      puppies and increased with increasing age of the animals. Thus in ontogenesis,
      the extent of endothelium-dependent relaxation and neurogenic contraction of the
      thoracic aorta displayed an opposite trend. The acetylcholine-induced relaxation
      was fully operative already in fetuses and puppies and its extent was declining
      toward adulthood, whereas the neurogenic contraction was hardly detectable in
      fetuses, increasing in puppies, and showed the highest values in adults.

PMID- 9152968
TI  - Treatment of aggressive non-Hodgkin's lymphoma in adults--are we doing any
      better?
AB  - Great improvement in the treatment of patients with aggressive non-Hodgkin's
      lymphoma (NHL) has been obtained with the introduction of new combination
      chemotherapy regimens in the 1970s. The hope that there would be further
      improvement has waned during recent years due to the fact that some controlled
      studies did not reveal any better results using the new more intensive treatment
      regimens. This is the reason for the question: are we doing any better?

PMID- 9152969
TI  - Bronchiolitis obliterans presenting as subcutaneous emphysema and
      pneumomediastinum: a case report.
AB  - We describe a woman post allogeneic bone marrow transplantation (BMT), who
      presented to the emergency room with subcutaneous emphysema and pneumomediastinum
      as the first manifestation of bronchiolitis obliterans complicating mild chronic
      graft versus host disease (GVHD). In contrast to other patients with
      pneumomediastinum described in the literature, this patient suffered from only
      mild GVHD. She did not receive methotrexate as GVHD prophylaxis, and the
      pneumomediastinum was a presenting manifestation rather than a terminal event. In
      addition, this is the first description of subcutaneous emphysema with this
      setting. Therefore, bronchiolitis obliterans should be highly suspected in post
      BMT patients presenting with pneumomediastinum and subcutaneous emphysema, and
      prompt therapy should be initiated.

PMID- 9152970
TI  - Tolerability and efficacy of GM-CSF [Leucomax] in patients with small cell lung
      cancer treated with intensive chemotherapy.
AB  - The aim of this study was to evaluate tolerability and efficacy of Leucomax
      (Sandoz/Schering Plough) used for neutropenia in patients with small cell lung
      cancer (SCLC) treated with etoposide and cisplatin. The potential influence of
      granulocyte-macrophage colony stimulating factor (GM-CSF) on chemotherapy
      relative dose intensity (RDI) was also evaluated. The chemotherapy used was the
      following, cisplatin 50 mg m-2 i.v. 1 and 7 day, etoposide 170 mg m-2 i.v. 3-5
      days, q 3-4 weeks. Patients received a median of six cycles (range 2-8) over 4-36
      weeks (median: 20). Thirty-two consecutive patients were treated, six were
      excluded. Eleven patients received GM-CSF 5 micrograms kg-1 s.c. due to absolute
      neutrophil count (ANC), 1000/mm3 until recovery (ANC > 2000 mm3) or during 7
      days, and thereafter prophylactically 24 hours post subsequent chemotherapy
      cycles for 7 days. Four patients received single GM-CSF course during the
      terminal disease phase. In 11 patients, there was no neutropenia requiring GM-CSF
      during the whole treatment course. Toxicity of chemotherapy was high, including
      thrombocytopenia, neutropenia, anaemia, mucositis, fever and hypotension. GM-CSF
      toxicity was the following, first dose reaction-one patient, local erythema-two
      patients, arthralgia-one patient, hypotension, chills, fever requiring GM-CSF
      discontinuation one patient RDI of cisplatin/etoposide was 0.77/0.62 in GM-CSF
      group, and 0.90/ 0.80 in patients who didn't receive Leucomax. Overall objective
      response rate to chemotherapy and complete response rate were 80% (21/26), 26%
      (7/26) and median survival of all patients was 10 months. Median disease free
      survival was 8 months. Four patients are alive, two patients lost during
      progression, 20 died. Administration of GM-CSF did not appear to improve RDI of
      chemotherapy, overall response rate (RR) nor survival in this phase I/II clinical
      study. RDI of chemotherapy was reduced in patients receiving GM-CSF due to
      thrombocytopenia and/or extrahaematologic toxicity of chemotherapy.

PMID- 9152971
TI  - Atypical clonal T-cell proliferation in infectious mononucleosis.
AB  - An atypical case of infectious mononucleosis characterized by fever, acute
      tonsillitis, and bilateral cervical adenopathy is reported in a previously
      healthy young man. Although serology was positive for the Epstein-Barr virus, the
      patient did not display peripheral blood lymphocytosis or atypical, reactive
      lymphocytes. The patient's tonsilar tissue revealed an expanded T-zone of
      diffuse, monomorphous lymphocytes suggestive of lymphoma. Immunophenotypic
      analysis of the tonsilar tissue demonstrated more than 90% expression of pan-T
      markers, while pan-B markers were positive in 5-10% of the interfollicular T-zone
      cells and in 90% of germinal centre cells. In situ hybridization with a probe
      specific for EBER1 demonstrated positive staining in approximately 1% of the
      interfollicular tonsilar lymphocytes. Finally, Southern blot analysis of tonsilar
      tissue demonstrated a clonal rearrangement of the T-cell receptor gene. The
      patient recovered from his infection and remains in good health years after
      presenting with his illness. This case illustrates that T-cell clonality must be
      evaluated with caution in the setting of a viral infection and can occur in
      association with benign, self-limited infectious mononucleosis.

PMID- 9152972
TI  - Utility of bisphosphonates in treating bone metastases.
AB  - Bone is the most common site of metastases from breast and prostate cancer, and
      bone destruction is characteristic of multiple myeloma. Increased osteoclast
      activity plays a key role in cancer-induced bone destruction. Bisphosphonates
      reduce osteoclastic bone resorption through various mechanisms as yet not fully
      elucidated. Bisphosphonates have proven to be effective in the treatment of tumor
      induced hypercalcaemia. Several clinical trials indicated that these compounds
      can positively influence many aspects of neoplastic bone disease, however, many
      questions regarding their long-term efficacy and optimal therapeutic schedule
      await clarification from well-designed clinical trials.

PMID- 9152976
TI  - Parity for mental illness--the half-full glass.

PMID- 9152975
TI  - Medulloblastoma in a patient successfully treated for immature teratoma of the
      ovary.
AB  - We report a case of medulloblastoma as a secondary malignancy in a patient
      treated for immature teratoma of the ovary (ITO). ITO is a rare but curable tumor
      of the ovary using combination chemotherapy. There is a great deal of interest in
      the long-term effects of chemotherapy in these patients. Once regarded as fatal
      not many series of patients with ITO have been reported with the long follow up
      as in the present case. This case may start a debate on the susceptibility of
      central nervous system tumors following chemotherapy in patients with ITO.

PMID- 9152973
TI  - Clinical and laboratory diagnosis of invasive candida infection in neutropenic
      patients.
AB  - Cancer patients, especially those with acute leukaemia, represent a group that
      has the greatest risk for deep fungal infection. Almost no cases were seen before
      the advent of modern chemotherapy, and prior to the availability of antibacterial
      agents, less than 5% of patients with acute leukaemia died of fungal infection.
      These infections are now responsible for 40% or more of the deaths at some
      institutions. Candida species continues to be the most common fungal pathogen.
      Rapid and specific diagnosis of invasive candiosis enabling early effective
      therapy is therefore an important measure for reducing mortality in patients.
      Here the current status of clinical and laboratory diagnosis of invasive candida
      infection in neutropenic patients is discussed and recommendations made as to
      future development programmes.

PMID- 9152974
TI  - Acute promyelocytic leukaemia in the all trans retinoic acid era.
AB  - Bleeding diathesis is a common complication of acute promyelocyctic leukaemia
      (APL). Multiple haemostatic defects are found in most patients with APL, which
      often worsen following cytoreductive chemotherapy. Besides thrombocytopenia, most
      patients develop disseminated intravascular coagulation, systemic fibrinolysis or
      both. A major aim in treating haemostatic defects of APL is to prevent death or
      disability from bleeding until chemotherapy clears the malignant promyelocytes
      from the blood and bone marrow. The therapeutic options are discussed in this
      review and practical guidelines for treatment are outlined.

PMID- 9152977
TI  - Mechanism of Alzheimer neurofibrillary degeneration and the formation of tangles.

PMID- 9152978
TI  - Catch me if you can: are catechol- and indoleamine genes pleiotropic QTLs for
      common mental disorders?

PMID- 9152980
TI  - Remodeling of cortical motor representations after stroke: implications for
      recovery from brain damage.

PMID- 9152979
TI  - ICE and apoptosis.

PMID- 9152981
TI  - Transcriptional pharmacology of neurodegenerative disorders: novel venue towards
      neuroprotection against excitotoxicity?

PMID- 9152982
TI  - REM sleep and amygdala.

PMID- 9152983
TI  - Activity-dependent synaptic plasticity: a new face of action for neurotrophins.

PMID- 9152984
TI  - Genetic linkage and bipolar affective disorder: progress and pitfalls.
AB  - The history of linkage studies in bipolar affective disorder is a convoluted
      affair punctuated by upswings and setbacks, hope and skepticism. Advances in
      genomics and statistical techniques, and the availability of well-characterized
      clinical samples, have bolstered the search for disease genes, leading to a new
      crop of findings. Indeed, recent reports of putative loci on chromosomes 18, 21,
      X, 4, 6, 13 and 15 have rekindled a sense of optimism. The new findings are
      reviewed and scrutinized, with implications for future research.

PMID- 9152985
TI  - Dissecting the genetic complexity of schizophrenia.
AB  - Twin, adoption and family studies have provided overwhelming but indirect
      evidence for a significant genetic contribution to the etiology of schizophrenia.
      More recent studies exploiting a plethora of highly polymorphic genetic markers
      provide a more direct approach to the identification and localization of genes.
      Current investigative efforts to identify schizophrenia susceptibility genes
      include diverse approaches such as linkage analysis, association studies, search
      for chromosomal abnormalities, analysis of disorders or syndromes with simple
      inheritance that overlap phenotypically with schizophrenia, studies of genetic
      anticipation and efforts to facilitate genetic analysis by reducing the
      phenotypic complexity of the disease. For the first time, after many years, there
      are now several promising findings, as well as replication efforts that inspire a
      certain degree of confidence in them.

PMID- 9152986
TI  - No association between the serotonin transporter gene regulatory region
      polymorphism and the Tridimensional Personality Questionnaire (TPQ) temperament
      of harm avoidance.
AB  - A functional polymorphism in the upstream regulatory region of the serotonin
      transporter gene has been recently reported to be associated with anxiety-related
      traits assessed by the NEO-PI-R. Individuals both hetero- and homozygous for the
      short form of a highly repetitive regulatory element in this gene have
      significantly higher neuroticism scores. We have attempted to replicate these
      findings in a normal cohort of 120 individuals, whom we have previously examined
      for association between personality dimensions and other serotonergic and
      dopaminergic receptor polymorphisms. The Tridimensional Personality Questionnaire
      (TPQ) was used to assess personality dimensions in this cohort. No association
      was observed in the present study between individuals grouped by the long and
      short form of the transporter gene and any of the personality dimensions measured
      by the TPQ including Harm Avoidance, which incorporates many aspects of anxiety
      and is correlated with NEO-PI-R Neuroticism.

PMID- 9152987
TI  - Inhibition of the interleukin-1 beta converting enzyme family rescues neurons
      from apoptotic death.
AB  - The interleukin-1 beta converting enzyme (ICE) family of cysteine proteases has
      been implicated in apoptosis. This study tested the effects of a novel pan-ICE
      family inhibitor, bocaspartyl(OMe)-fluoromethylketone (boc-Asp-CH2F), against low
      potassium-induced apoptosis of cultured rat cerebellar granule neurons (CGN). A
      single application of this cell-permeant compound (20 microM) inhibited apoptotic
      cell death up to 48 h. Classical apoptotic changes were monitored by fluorescence
      microscopy, DNA fragmentation and scanning electron microscopy (SEM). A control
      peptidic fluoromethylketone (boc-Thr-CH2F), and inhibitors to calpain (Ac-Leu-Leu
      norleucinal), cathepsin B (Z-Phe-Ala-CH2F), and CPP32-like proteases (Z-DEVD
      CH2F), failed to prevent apoptotic death. An 35S-methionine incorporation assay
      verified that, unlike cycloheximide, boc-Asp-CH2F did not inhibit protein
      synthesis, hence excluding this as a rescuing mechanism. Although ICE was not
      detected by northern blot analysis, both CPP32 and Nedd2 expression were found to
      increase during apoptosis. Kinetic assays with cell extracts from boc-Asp-CH2F
      treated neurons measured reduced rates of cleavage for DEVD-pNA and LEVD-pNA. At
      present, ICE-like proteases remain viable candidates for mediating neuronal
      death.

PMID- 9152988
TI  - Association of polymorphisms of dopamine D2 receptor (DRD2), and dopamine
      transporter (DAT1) genes with schizoid/avoidant behaviors (SAB).
AB  - The dopaminergic system, and in particular the dopamine D2 receptor, has been
      implicated in reward mechanisms in the brain. Dysfunction of the D2 dopamine
      receptors leads to aberrant substance-seeking behaviors (ethanol, drugs, tobacco,
      and food) and other related behaviors (pathological gambling, Tourette's
      disorder, attention-deficit/hyperactivity disorder). This is the first study
      supporting a strong association between the dopamine D2 receptor Taq A1 allele
      with schizoid/avoidant behavior (SAB). Additionally, an albeit weaker association
      between the 480-bp VNTR 10/10 allele of the dopamine transporter (DAT1) gene with
      SAB was similarly found.

PMID- 9152990
TI  - Excess dopamine D4 receptor (D4DR) exon III seven repeat allele in opioid
      dependent subjects.
AB  - Only in the past decade has a role of heredity in substance abuse been
      established as a result of extensive twin and family studies. More recently,
      several candidate genes have been investigated for their possible role in
      alcoholism and cocaine abuse. Specific genetic factors in opioid substance abuse
      have not been investigated in man, although animal studies suggest that
      quantitative trait loci (QTLs) can be identified that predispose mice both to
      morphine and alcohol preference. Central dopaminergic pathways figure prominently
      in drug-mediated reinforcement suggesting that dopamine receptors are likely
      candiadates for association with substance abuse in man. In addition, we recently
      reported an association between a human personality trait, Novelty Seeking and
      the long alleles (represented chiefly by the 7-repeat) of the D4 dopamine
      receptor (D4DR) exon III polymorphism. The personality trait of Novelty Seeking
      is also more pronounced in substance abusers, who score higher in this dimension
      than control subjects. The twin role of dopamine receptors in mediating Novelty
      Seeking and drugreinforcement prompted us to examine a group of Israeli heroin
      addicts for prevalence of the D4DR repeat polymorphism. We now show that the 7
      repeat allele is significantly over-represented in the opioid-dependent cohort
      and confers a relative risk of 2.46. To our knowledge this is the first report of
      an association between a specific genetic polymorphism and opioid addiction.

PMID- 9152989
TI  - Evidence of linkage between the serotonin transporter and autistic disorder.
AB  - The serotonin transporter gene (HTT) is a primary candidate in autistic disorder
      based on efficacy of potent serotonin transporter inhibitors in reducing rituals
      and routines. We initiated a candidate gene study of HTT in trios consisting of
      probands with autistic disorder and both parents. Preliminary
      transmission/disequilibrium test (TDT) analysis with 86 families revealed no
      evidence for linkage or linkage disequilibrium between autistic disorder and a
      polymorphism in the second intron of HTT. However, preferential transmission of a
      short variant of the HTT promoter was found in the same 86 trios (TDT chi 2 =
      4.69, 1 d.f., P = 0.030). In further analyses, we considered haplotypes of the
      HTT promoter variant and second intron locus as alleles in a multiallelic TDT.
      Results confirmed the significance of the effect of this region (TDT chi 2 =
      11.85, 4 d.f., P = 0.018). This provides preliminary evidence of linkage and
      association between HTT and autistic disorder.

PMID- 9152991
TI  - Possible mechanisms for atrophy of the human hippocampus.
AB  - Recently published work using MRI to image the human brain has revealed that the
      hippocampal formation undergoes a selective atrophy in diverse conditions such as
      Cushing's syndrome, post-traumatic stress disorder, recurrent depressive illness,
      normal aging preceding dementia and in Alzheimer's disease. Hippocampal shrinkage
      is usually accompanied by deficits in declarative, episodic, spatial and
      contextual memory performance and the hippocampal changes provide a neural
      substrate for changes in cognitive function that have been recognized to
      accompany these various conditions. The hippocampus has long been known as a
      target of stress hormones, and it is an especially plastic and vulnerable region
      of the brain. However, the prominence of the hippocampus as a glucocorticoid
      target has obscured the fact that other factors besides glucocorticoid hormones
      are involved in the process of hippocampal atrophy. Excitatory amino acids and
      NMDA receptors are prominent in their involvement in an animal model of
      hippocampal atrophy as well as in neuronal death. Further-more, the finding of
      hippocampal atrophy does not necessarily imply a permanent loss of cells, and
      this aspect deserves careful investigation, both to analyze the underlying
      anatomical changes and to investigate the possibility of pharmacological
      treatment to reverse the process. In cases where atrophy is due to cell loss, the
      time course of the disease process will provide much useful information about
      mechanism and offer the possibility of early intervention to arrest or slow the
      pathological process.

PMID- 9152992
TI  - Involvement of phospholipase A2 in neurodegeneration.
AB  - Phospholipases A2 are a heterogeneous class of enzymes that hydrolyse fatty acids
      from the sn-2 2 position of membrane phospholipids. Prolonged stimulation of
      phospholipase A2 may damage membrane integrity, not only because of the loss of
      essential phospholipid from the lipid bilayer but also as a result of an
      uncontrollable Ca2+ influx. The increased levels of intracellular Ca2+ may be
      responsible for enhanced lipolysis, proteolysis and DNA fragmentation. This
      process along with the accumulation of lipid peroxidation products may be
      associated with neurodegeneration in acute neural trauma (ischemia, head and
      spinal cord injuries) and neurodegenerative diseases (Alzheimer's disease).

PMID- 9152993
TI  - Sodium/calcium exchanger in rat olfactory neurons.
AB  - The chemo-electrical transduction process in olfactory neurons is accompanied by
      a rapid and transient increase in intracellular calcium concentrations. The
      notion that Na+/Ca2+ exchanger activities may play a major role in extruding
      calcium ions out of the cell and maintaining Ca2+ homeostasis in olfactory
      receptor cells was assessed by means of laser scanning confocal microscopy in
      combination with the fluorescent indicators Fluo-3 and Fura-Red. The data
      indicate that high exchanger activity, which was inhibited by amiloride
      derivatives, is located in the dendritic knob and probably in the olfactory
      cilia. This result was supported by experiments using specific antiserum raised
      against retinal Na+/Ca2+ exchanger protein which labelled an immunoreactive
      protein of 230 kDa in Western blots from olfactory tissue and strongly stained
      the ciliary layer of the olfactory epithelium.

PMID- 9152994
TI  - In vivo hypoxia-induced neuronal damage in dentate gyrus of rat hippocampus:
      changes in NMDA receptors and the effect of MK-801.
AB  - Hypoxia is a major cause of ischaemia-induced neuronal damage. In the present
      study, we examined the effects of in vivo hypoxia on N-methyl-D-aspartate
      receptors (NMDAR) in the rat hippocampus. This model of in vivo hypoxia involved
      placing rats in a hypoxic chamber containing 5% O2 and 95% N2 for 30 min. In the
      hippocampus, neuronal cells in the CA3, the hilus of the dentate gyrus and the
      dentate gyrus (DG) were damaged. In the CA1, which is known to be vulnerable to
      ischaemic damage, neuronal cells did not show hypoxia-induced damage. In vivo
      hypoxia-induced damage caused morphological changes in neuronal cells, such as
      shrunken, spindle or triangular shapes accompanied by pyknotic nuclei, but did
      not induce the loss of neuronal cells. On the other hand, the number of binding
      sites for [3H]-1-[1-(2-thienyl)cyclohexyl]-3,4-piperidine hydrochloride (TCP)
      gradually decreased on and after 7 days, and then maximally decreased by 25% at
      21 days after hypoxia. The number of NMDAR1-immunopositive cells was decreased by
      22% in the DG, but was unchanged in the CA3. Furthermore, we examined the effect
      of a non-competitive NMDA antagonist, (+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,b]
      cyclohepten-5,10-imine hydrogen maleate (MK-801), on against in vivo hypoxia. The
      administration of MK-801 (3 mg/kg, i.p.), 30 min before hypoxia treatment, partly
      protected against neuronal damage in the DG, but not in the CA3. These results
      suggest that hypoxia-induced neuronal damage in the DG involves, in part, the
      activation of NMDAR.

PMID- 9152995
TI  - Heparin promotes beta-secretase cleavage of the Alzheimer's amyloid precursor
      protein.
AB  - In Alzheimer's disease, abnormal processing of the amyloid precursor protein
      (APP) is thought to play an important role in amyloid deposition. We investigated
      the effect of heparin, a highly sulfated glycosaminoglycan related to heparan
      sulfate, on the secretion of the beta-secretase cleavage product of APP (sAPP
      beta) in a human neuroblastoma cell line. Heparin induced an increase in the
      secretion of total APP, and an even greater relative increase in the secretion of
      sAPP beta. The effect on sAPP beta was specific to heparin. These data support
      the hypothesis that highly sulfated heparan sulfate proteoglycans may promote
      amyloidogenic pathways of APP metabolism.

PMID- 9152996
TI  - Low selenium diet increases the dopamine turnover in prefrontal cortex of the
      rat.
AB  - It has been proposed that interaction of catecholamines and indoleamines with
      free radicals may result in the formation of endogenous neurotoxins. In order to
      better understand the mechanisms involved in neurodegenerative disorders showing
      evidence of oxidative stress, we have studied the basal concentrations and the
      turnover rates of dopamine, noradrenaline, serotonin and their metabolites in the
      prefrontal cortex of rats that were fed on control or low selenium diets.
      Nutritional deficit of selenium decreases the brain antioxidant protection in
      experimental conditions by the decrease in glutathione peroxidase activity. The
      dopamine and serotonin turnover increased and noradrenaline and 5-hydroxy-3
      indoleacetic acid turnover decreased compared to experimental control animals.
      The increase of dopamine turnover in experimental rats was accompanied by an
      increase in tyrosine hydroxylase activity. These results suggest that the
      decrease of brain protection against oxidative damage could induce brain damage
      by disturbing the turnover rate of some monoamines.

PMID- 9152997
TI  - Glutamate-stimulated secretion of amyloid precursor protein from cortical rat
      brain slices.
AB  - The aim of this study was to determine whether L-glutamate, a major excitatory
      transmitter in the cerebral cortex, modulates the proteolytic cleavage of the
      amyloid precursor protein (APP) in the brain through specific receptor
      activation. Native rat brain cerebral cortical slices were stimulated either with
      L-glutamate or various glutamate receptor agonists, and the soluble APP
      derivatives released into the incubation medium were assayed by Western blot
      analysis. Immunoprecipitation with specific antibodies revealed that in the
      medium only secretory forms of APP lacking intact C-terminus were present,
      whereas in the brain slices both C- and N-terminal intact APP products were
      detectable. L-glutamate induced the release of secretory APP from cortical slices
      in a concentration-dependent but biphasic manner, with the highest release at 50
      microM L-glutamate and smaller effects at higher glutamate concentrations. To
      determine whether the effect of L-glutamate is mediated through distinct
      glutamate receptor subtypes, brain slices were incubated in the presence of
      various specific glutamate receptor agonists. Activation of the alpha-amino-3
      hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor with 50 nM (RS)
      bromohomoibotenic acid resulted in a reduced release of secretory APP by 17% +/-
      3 (P < 0.01, one tailed Student's t-test) compared to the incubation without any
      drug. Stimulation of the metabotropic glutamate receptor with 50 nM (2S,3S,4S)
      alpha-(carboxycyclopropyl)-glycine (L-CCG-I) led to an enhanced release of
      secretory APP by 39% +/- 3 (P < 0.001), whereas activation of the N-methyl-D
      aspartate (NMDA) receptor with 50 nM (1R,3R)-1-aminocyclopentane-1,3-dicarboxylic
      acid ((1R,3R)-ACPD) did not significantly change the secretion of APP compared to
      the incubation without any drug. The data suggest that: (i) cortical
      glutamatergic neurotransmission is involved in APP metabolism; and (ii) the
      stimulation of APP cleavage in cerebral cortical brain slices is mainly mediated
      by the metabotropic but not the NMDA glutamate receptor subtype, whereas the AMPA
      receptor subtype seems to inhibit the secretory path of APP processing.

PMID- 9152998
TI  - [3H]WAY-100635 for 5-HT1A receptor autoradiography in human brain: a comparison
      with [3H]8-OH-DPAT and demonstration of increased binding in the frontal cortex
      in schizophrenia.
AB  - WAY-100635 is the first selective, silent 5-HT1A (5-hydroxytryptamine1A,
      serotonin-1A) receptor antagonist. We have investigated the use of [3H]WAY-100635
      as a quantitative autoradiographic ligand in post-mortem human hippocampus, raphe
      and four cortical regions, and compared it with the 5-HT1A receptor agonist,
      [3H]8-OH-DPAT. Saturation studies showed an average Kd for [3H]WAY-100635 binding
      in hippocampus of 1.1 nM. The regional and laminar distributions of [3H]WAY
      100635 binding and [3H]8-OH-DPAT binding were similar. The density of [3H]WAY
      100635 binding sites was 60-70% more than that of [3H]8-OH-DPAT in all areas
      examined except the cingulate gyrus where it was 165% higher. [3H]WAY-100635
      binding was robust and was not affected by the post-mortem interval, freezer
      storage time or brain pH (agonal state). Using [3H]WAY-100635, we confirmed an
      increase of 5-HT1A receptor binding sites in the frontal cortex in schizophrenia,
      previously demonstrated with [3H]8-OH-DPAT. Compared to [3H]8-OH-DPAT, [3H]WAY
      100635 has two advantages: it has a higher selectivity and affinity for the 5
      HT1A receptor, and it recognizes 5-HT1A receptors whether or not they are coupled
      to a G-protein, whereas [3H]8-OH-DPAT primarily detects coupled receptors. Given
      these considerations, the [3H]WAY-100635 binding data in schizophrenia clarify
      two points. First, they indicate that the elevated [3H]8-OH-DPAT binding seen in
      the same cases is attributable to an increase of 5-HT1A receptors rather than any
      other binding site. Second, the enhanced [3H]8-OH-DPAT binding in schizophrenia
      reflects an increased density of 5-HT1A receptors, not an increased percentage of
      5-HT1A receptors which are G-protein-coupled. We conclude that [3H]WAY-100635 is
      a valuable autoradiographic ligand for the qualitative and quantitative study of
      5-HT1A receptors in the human brain.

PMID- 9152999
TI  - Mechanism of modulation of [3H]raclopride binding to dopaminergic receptors in
      rat striatal membranes by sodium ions.
AB  - The mechanism of modulation of [3H]raclopride binding to dopaminergic receptors
      in rat brain striatal membranes by sodium ions was studied by means of
      equilibrium and kinetic measurements. Among different mono- and divalent cations
      studied, only sodium and lithium ions significantly enhanced [3H]raclopride
      binding to rat striatal membranes, but the effect of lithium was considerably
      smaller if compared with that of sodium. The equilibrium binding studies revealed
      that the increase in Na+ concentration from 0.5 to 150 mM increased both the
      radioligand affinity and the number of binding sites. The meaning of these
      changes was established by kinetic studies, which yielded hyperbolic plots of
      [3H]raclopride binding rate constants over the radioligand concentration. These
      plots correspond to the two-step ligand binding reaction mechanism, involving
      fast binding equilibrium followed by a slow isomerization of the receptor
      antagonist complex. Sodium ions did not influence the antagonist affinity for the
      receptor sites in the first step of the binding process, nor the rate of
      isomerization of the receptor-ligand complex, but slowed down the rate of
      deisomerization. This led to a change in the value of the receptor-ligand
      dissociation constant Kd determined under equilibrium conditions. The same change
      in deisomerization rate was also sufficient to alter the receptor density (Bmax),
      measured by the conventional ligand binding procedure.

PMID- 9153000
TI  - Structural analogues of ZAPA as GABAA agonists.
AB  - Structural analogues of ZAPA, Z-3-[(aminoiminomethyl)thio]prop-2-enoic acid, an
      isothiouronium analogue of GABA, are potent GABAA agonists as seen in the
      isolated guinea-pig ileum and in the facilitation of [3H]diazepam binding to rat
      brain membranes. Compounds with guanidino or amidine groups replacing the amino
      functionality of GABA were also found to be active. The highest activity was
      displayed by the isothiouronium salts in which the conformational flexibility of
      the molecule is restricted by a Z-substituted carbon-carbon double bond. A series
      of bis-isothiouronium compounds was prepared from aliphatic alpha, omega-bis
      thioureas as mixtures of E and Z adducts. Maximum GABAA agonist activity for this
      series was found with a C6-C8 carbon chain, and the results were consistent with
      an interaction at the GABAA receptor with only one end of the molecule, rather
      than the more potent effect expected of a molecule bridging two active sites.
      GABAA antagonist/partial agonist activity was observed on the guinea pig isolated
      ileum for a number of different analogue types, with the most potent being bis
      isothiouronium derivatives. None of the substituted derivatives of ZAPA was as
      active as ZAPA itself, and maximum GABAA activity was found in the n-pentyl and n
      hexyl analogues.

PMID- 9153001
TI  - Gangliosides of dogfish (Squalus acanthias) brain.
AB  - Eighteen gangliosides were isolated from dogfish (Squalus acanthias) brain, and
      their structures and compositions were determined by methylation analysis,
      enzymatic hydrolysis and partial hydrolysis with mild acid. Tetra- and
      pentasialogangliosides were also analysed by liquid secondary ion mass
      spectrometry. The dogfish brain gangliosides were characterized by a variety of
      molecular species. The most abundant ganglioside was GM2 (22.8% of the total
      sialic acid content), followed by GQ1c (16.0%), GP1c (13.4%), and GD2 (12.5%).
      The abundance of gangliosides containing a gangliotriaose core (GM2 and GD2), and
      c-series polysialogangliosides (GQ1c and GP1c) was a prominent feature of dogfish
      brain, differing from the brain gangliosides of teleosts and other vertebrates. A
      battery of trisialogangliosides was also found. A ganglioside which had an a- and
      alpha-series hybrid-structure (IV3NeuAc,III6NeuAc,II3NeuAc-Gg4Cer) comprised 1.4%
      of the total. The major fatty acids comprised 16:0, 18:0, 18:1, 22:1 and 24:1.
      The gangliosides with a gangliotriaose core predominantly contained 22:1.
      Sphinganine and 4-sphingenine comprised the long-chain bases.

PMID- 9153002
TI  - Effects of kyotorphin (L-tyrosyl-L-arginine) ON[3H]NG-nitro-L-arginine binding to
      neuronal nitric oxide synthase in rat brain.
AB  - L-Tyrosyl-L-arginine (kyotorphin) is known as an endogenous analgesic
      neuropeptide. We examined whether kyotorphin and other arginine-containing
      neuropeptides were endogenous substrates for neuronal nitric oxide synthase (NOS)
      in the rat brain. Cytosol fractions of the rat cerebellum contained higher
      concentrations of neuronal NOS (nNOS) than endothelial NOS. In rat cerebellar
      cytosol, the binding activity of [3H]NG-nitro-L-arginine (NNA) was inhibited
      equally by L-arginine (L-Arg), kyotorphin, and L-leucyl-L-Arg (a kyotorphin
      receptor antagonist). Binding activities were inhibited to lesser degrees by
      fibronectin active fragments, bradykinin, and dynorphin A, but were not inhibited
      by L-tyrosyl-D-Arg or substance P. Interestingly, the inhibition of [3H]NNA
      binding by kyotorphin was attenuated by inhibitors of kyotorphin-hydrolyzing
      peptidases (KTPases) such as bestatin and arphamenine B. These results suggest
      that kyotorphin is degraded to L-Arg by KTPases, which in turn may act as
      substrate for nNOS.

PMID- 9153004
TI  - Experiences in the use of event related potentials in the evaluation of cognitive
      processes.

PMID- 9153005
TI  - Bereitschaftspotential to inner and overt speech.

PMID- 9153003
TI  - Alterations in the turnover rate of dopamine D1 but not D2 receptors in the adult
      rat neostriatum after a neonatal dopamine denervation.
AB  - Adult rats that were treated with intracerebral ventricular injection of 6
      hydroxydopamine (6-OHDA) as neonates exhibit a profound loss of nigrostriatal
      dopamine innervation in addition to a variety of other neurochemical and
      anatomical changes, including alterations in the number of neostriatal D1 and D2
      receptor binding sites. In the present study, the turnover of neostriatal
      dopamine D1 and D2 receptors was measured in rats previously treated with 6-OHDA
      or ascorbic acid vehicle as neonates at various time intervals after peripheral N
      ethoxycarbonyl-2-ethoxy-1, 2-dihydroquinoline (EEDQ, 10 mg/kg) administration.
      Dopamine receptors were labelled with [3H]SCH23390 (D1) and [3H]raclopride (D2),
      while the degree of dopamine denervation was assessed by the measurement of
      neostriatal dopamine, homovanillic acid and dihydroxyphenylacetic acid content.
      Two days after acute EEDQ treatment, the maximal binding capacity (Bmax) of
      [3H]SCH23390 and [3H]raclopride binding was significantly decreased to 58 and 32%
      of control values, respectively, without any significant alteration in their
      equilibrium dissociation constants (Kd). A time-dependent increase in the density
      of [3H]SCH23390 and [3H]raclopride binding was observed in both treatment groups
      following a single dose of EEDQ. The rate of recovery of D1 receptors was
      significantly slower in the 6-OHDA-lesioned animals as compared to controls with
      a half-life of 103 compared to 53 h, respectively. No differences were observed
      in the rate of recovery of D2 receptors in these two treatment groups. These data
      are consistent with the findings of decreased expression of D1 receptors in
      neonatal 6-OHDA-lesioned rats owing to decreased receptor synthesis, and further
      suggest that in this model the up-regulation of D2 receptors is a result of a
      post-transcriptional mechanism, such as an increased rate of post-synthetic
      maturation.

PMID- 9153006
TI  - Brain death in infants and children.

PMID- 9153007
TI  - Latency of eye movement and mean latency of eye movement within REM sleep. The
      methods and the applications.

PMID- 9153008
TI  - How long should eeg be monitored in order to diagnose epilepsy: 24 or 48 hours?

PMID- 9153009
TI  - Clinical neurophysiology as a medical speciality in Finland.

PMID- 9153010
TI  - Multi-MUP EMG analysis in clinical routine.
AB  - A new quantitative motor unit potential (MUP) analysis method, called Multi-MUP
      analysis, is described. Multi-MUP analysis is a type of decomposition analysis of
      the EMG signal. At each recording site six different MUPs may be recorded during
      an epoch of 4.8 sec. A study of 20-30 MUPs including editing takes 3-7 minutes.
      Compared to many other MUP analysis methods it is faster and more user friendly,
      therefore it can be used in daily routine EMG analysis. The differences to
      methods based on manual analysis, spike-triggered averaging, template matching
      and decomposition are discussed. The main advantages of Multi-MUP analysis are:
      (1) quick acquisition of many MUPs; (2) simultaneous collection of several MUPs
      at one recording site; (3) possibility to analyze not only low threshold MUPs;
      (4) less bias in the selection of MUPs and (5) the reproducibility of the results
      that allow the same reference values to be used in different laboratories. So far
      we have successfully used this method in clinical routine for four years on more
      than five thousand patients.

PMID- 9153011
TI  - What is really important in MUAP--is it its shape?

PMID- 9153012
TI  - Anterior tibial dystrophy (late onset foot drop muscular dystrophy with rimmed
      vacuoles).

PMID- 9153013
TI  - Reorganization of motor units in amyotrophic lateral sclerosis.

PMID- 9153014
TI  - Nerve conduction velocity in severe childhood spinal muscular atrophy (SMA type
      I).

PMID- 9153015
TI  - Motor cortex threshold in Wilson's disease (transcranial magnetic stimulation).

PMID- 9153016
TI  - The normative data in biceps brachii, first interosseus, quadriceps femoris and
      tibialis anterior muscles in EMG-LAB system.

PMID- 9153017
TI  - The contribution to spasticity qualification in neurological rehabilitation of
      patients with upper motor neuron syndrome.

PMID- 9153018
TI  - Sympathetic skin response (SSR) in multiple sclerosis.
AB  - The function of the autonomic system in multiple sclerosis (MS) is often
      afflicted. In order to reveal the presence of autonomic disturbances examination
      of sympathetic skin response (SSR), as a simple non-invasive method of the
      evaluation of conduction in autonomic nervous system, was performed in 25
      patients with clinically defined MS. The diagnosis was confirmed by MRI and
      evoked potentials studies. Bimodal type of stimulation was used: the median nerve
      was stimulated, then the auditory stimulus (burst) was presented to the patient.
      Responses were recorded simultaneously from the palms and soles. SSR was abnormal
      in 19 patients (76%). Absence of the response from lower limbs and normal
      response from upper limbs were found in 6 patients (24%), increase in latency and
      decrease in amplitude from upper and lower limbs were found in 8 patients (32%)
      and increase in latency, decrease in amplitude of the response from upper limbs
      with absence of the response from lower limbs were found in 5 patients (20%). SSR
      appears to be a simple and effective method of assessing sympathetic disturbances
      in multiple sclerosis.

PMID- 9153019
TI  - Bilateral field interactions, hemispheric specialization and evoked potential
      interhemispheric transmission time.
AB  - The interrelationship between bilateral visual field processing, hemispheric
      specialization and interhemispheric transmission time (IHTT) was examined in two
      experiments in order to test two theories regarding callosal function and
      lateralized visual processing. Contrary to both theoretical speculations [Braun,
      Neuropsychology Review, Vol. 3, pp. 321-365, 1992] and a recent report [Nowicka
      et al., Neuropsychologia, Vol. 34, pp. 147-151, 1996], the directional asymmetry
      in evoked potential measures of IHTT did not vary with task differences in
      indices of hemispheric specialization. IHTT was faster from right to left
      hemispheres regardless of visual field advantage for the task. Similarly,
      patterns of correlation between IHTT and bilateral field advantage did not change
      between verbal and spatial matching tasks, despite differences in visual field
      advantage. Since the latter data did not consistently support the Brown and
      Jeeves [Neuropsychologia, Vol. 31. pp. 1267-1281, 1993] hypothesis, an
      alternative hypothesis involving hemispheric asymmetries in attention rather than
      processing specialization was proposed.

PMID- 9153020
TI  - Influence of perceptual and semantic conflicts between the two halves of chimeric
      stimuli on the expression of visuo-spatial neglect.
AB  - We investigated how perceptual and semantic relationships between the left and
      right half of chimeric stimuli influence overt and covert visual processing by
      asking eight right brain damaged (RBD) patients with hemispatial neglect to
      identify complete, half-, and chimeric drawings. Chimeric stimuli belonged in one
      of four categories defined according to the perceptual and semantic relatedness
      between the two compounding hemi-figures. Thus, the hemi-figures could be related
      both perceptually and semantically, only perceptually, only semantically, or
      neither perceptually nor semantically. Although patients often appeared to base
      their report on the right part of the chimerics, the number of errors was minimal
      when conflicts between the two hemi-figures were maximal. Moreover, perceptual
      conflicts, which mainly affect the perception of the shape, appeared to influence
      the performance more than semantic conflicts. Since the analysis of shape
      incongruency is probably accomplished at early levels of information processing,
      the result suggests that preattentive analysis is largely spared in the
      experimental patients and that, in our task, bottom-up factors more than top-down
      factors modulate the expression of left neglect.

PMID- 9153021
TI  - The role of the hippocampus in recognition memory.
AB  - Amnesic patients with focal limbic lesions in the hippocampus demonstrate normal
      or near normal performance on the Warrington Recognition Memory Test (WRMT)
      suggesting that the hippocampi may not be critical structures in these tasks. To
      further investigate the role of the hippocampi in recognition memory we examined
      WRMT performance in 99 (44 right, 55 left) patients with unilateral temporal lobe
      pathology identified on MRI. The patients were divided into two groups. Group 1
      (n = 90) were patients with hippocampal sclerosis (40 right, 50 left). Group 2
      were patients with MRI evidence of hippocampal sclerosis and cortical dysgenesis,
      (4 right, 5 left). Analyses of variance revealed a significant interaction
      between laterality and pathology group for the recognition memory for words (RMW)
      task. The patients with left hippocampal sclerosis and cortical dysgenesis
      obtained significantly lower scores than the other patient groups. There was a
      significant effect of pathology group on the recognition memory for faces task
      (RMF). The patients with hippocampal sclerosis and cortical dysgenesis obtained
      lower scores than the patients with hippocampal sclerosis, regardless of the
      laterality of their pathology. Post-operative WRMT deficits in the right and left
      hippocampal sclerosis groups were material specific. The clinical utility of the
      WRMT in the pre-surgical investigation of temporal lobe epilepsy patients and the
      role of the hippocampus in recognition memory are discussed in the light of these
      findings.

PMID- 9153022
TI  - Dissociation of visual and spatial processing in working memory.
AB  - Although models of working memory originally included visuo-spatial memory as an
      undifferentiated component, recent work indicates that spatial location is
      separable from other visual characteristics. The evidence which is derived from
      interference, however, typically requires the division of conscious attention
      between primary and interference tasks. In the present experiments the
      differential effects of an unattended flickering surround upon serial recall of a
      central stimulus presentation were investigated. Colour changes in the surround
      created more interference than achromatic flicker when the task was to report
      either the colours or the patterns presented in the target. When the locations of
      the targets were required, however, the situation was reversed and the achromatic
      flicker created more interference than did the colour flicker. It is suggested
      that this double dissociation of identification and location is best understood
      in terms of differential involvement of the magnocellular and parvocellular
      pathways.

PMID- 9153023
TI  - Unconscious influences on amnesics' word-stem completion.
AB  - Amnesic patients and control subjects were asked to complete three-letter word
      stems under one of three retrieval conditions. In a direct condition, they were
      told to use the stems as retrieval cues for words that had just been presented in
      a study list. In an indirect condition, they were told to use the first word that
      came to mind with no reference made to the study list. Finally, in an
      oppositional condition, they were told to use the first word that came to mind
      unless it had appeared on the study list. During the study list presentation, the
      patients and controls had analyzed each word according to either semantic
      (associating to each word) or graphemic (counting letters with enclosed spaces)
      instructions. The results revealed that the control subjects produced a different
      number of study words during retrieval as a function of retrieval instructions
      and encoding condition. The amnesics, however, did not vary their performance as
      a function of retrieval instructions. Under all conditions, they completed the
      word-stems far more frequently with words from the study list than would be
      expected by chance and they consistently produced more semantic than graphemic
      responses. We concluded that semantic analysis might affect the fluency with
      which an item occurs for the amnesic, but that the item itself remains
      independent of the source of that fluency for these patients. Thus, the level of
      analysis performed on a word during study can affect the unconscious performance
      of amnesic patients but is unavailable for use during conscious retrieval.

PMID- 9153024
TI  - Word priming with brief multiple presentation technique: preservation in amnesia.
AB  - Many studies have shown relative preservation of word priming in subjects with
      mild amnesia, but some decrease in severe amnesia. This calls into question the
      degree of separation between implicit and explicit memory. Possible contamination
      of implicit memory tasks by impaired explicit memory strategies might be
      obscuring the actual dissociation between the two memory systems. We have
      developed a method of circumventing explicit memory contamination by using brief
      duration repeated primes below the awareness threshold of subjects. We have used
      this approach to evaluate the status of word priming in densely amnesic subjects.
      One group of amnesic subjects with alcoholic Korsakoff's syndrome and one group
      of normal elderly control subjects were tested for word priming on a speeded
      category membership decision task. Implicit or explicit encoding procedures were
      used in three different experiments. Results demonstrated that brief multiple
      presentation of words can offer a means of producing word priming in the absence
      of explicit recognition or recall of the primed words in both amnesic subjects
      and normal elderly control subjects. Moreover, there was no significant
      difference in the magnitude of the priming effect between these groups in the
      three experiments. These findings show that amnesic subjects can exhibit normal
      levels of word priming. They also suggest that amnesics retain the capacity to
      encode, store and retrieve information implicity, e.g. unintentionally.

PMID- 9153025
TI  - Priming arithmetic facts in amnesic patients.
AB  - In this study, amnesic patients showed significant repetition priming effects in
      arithmetic fact retrieval tasks. The results indicate that repetition priming
      effects in arithmetic depend not on explicit recognition, but on the activation
      of specific long-term representations of arithmetic facts. Processing
      dissociations between easy and difficult items suggest that the priming effects
      results from the stage of fact retrieval and not from peripheral activation. This
      claim is also supported by encoding and naming tasks, which showed only slight
      priming effects as compared to the priming found in calculation tasks.
      Significant priming was found for identical (5 x 6 and 5 x 6) and complement
      problems (5 x 6 and 6 x 5), the latter showing a smaller magnitude of priming.

PMID- 9153026
TI  - Impaired estimation of word occurrence frequency in frontal lobe patients.
AB  - Neuroanatomical correlates of the estimation of occurrence frequency have
      received little attention. This study investigates the possible role of the
      frontal lobe in estimating word occurrence frequency. A sample of 27 patients
      with frontal lesions were matched with normal controls by sex, age and years of
      education. Significant differences between patients and controls were found for
      frequency estimation, but not for item recognition. Studying accuracy of
      estimation as a function of actual frequency, the frontal group performed worse,
      especially at high frequencies of occurrence. As far as lesion lateralization is
      concerned, the right frontal subgroup performed worse than the control group in
      the estimation of frequency. Our results suggest that the prefrontal cortex plays
      a role in estimating word occurrence and that there is a dissociation between
      frequency memory and recognition memory, pointing to the involvement of two
      different cerebral systems.

PMID- 9153027
TI  - Cerebellar hypoplasia and frontal lobe cognitive deficits in disorders of early
      childhood.
AB  - A developmental chronometry hypothesis of early brain damage is suggested in
      which regions of the brain with a protracted course of postnatal development will
      be more vulnerable than earlier maturing areas to deleterious effects of early
      insult and, therefore, may become common sites of abnormality across many
      disorders originating in early childhood. Initial investigations of the
      cerebellum and frontal lobes are presented using MRI and neuropsychological
      measures. Planimetric measures of the cerebellar vermis (lobuli I-V and VI-VII)
      and pons, and neuropsychological frontal lobe measures were obtained from high
      functioning individuals with autism (A), survivors of acute lymphoblastic
      leukemia (ALL) with brain sequelae following radiation and chemotherapy, and from
      rigorously selected healthy controls (C). The neuropsychological results were
      clustered according to functions commonly related to frontal brain, posterior
      brain, and left and right hemispheres. The A and ALL groups, as compared to C,
      yielded modest but consistently reduced MRI measures for vermal lobuli I-V and VI
      VII. Hypoplasia of lobuli VI-VII was more marked than I-V. Performance on
      neuropsychological tests for frontal lobe functions was generally depressed in
      both groups, with more severe deficits in A. Between-group differences in verbal,
      visual-spatial, and emotional-social skills are discussed. The cerebellar and
      frontal brain deficits that are present in both clinical groups (A and ALL) may
      be common to other developmental and acquired disorders of early childhood. Such
      joint manifestation of cerebellar and frontal lobe abnormalities is in agreement
      with the concept of cerebellar significance for the development of higher
      cognitive functions.

PMID- 9153028
TI  - Human temporal lobe potentials in verbal learning and memory processes.
AB  - Animal experiments and lesion studies have shown the importance of temporal lobe
      structures for language and memory. We recorded intracranial cognitive potentials
      from the human lateral and medial temporal lobe in 26 patients with temporal lobe
      epilepsy undergoing presurgical evaluation, using a word- and a picture
      recognition paradigm. Neuropsychological testing included word fluency, verbal
      reasoning, sustained attention and a verbal learning memory test (VLMT), which
      was an adapted version of the Rey auditory verbal learning test. Word-specific
      N400-potentials elicited in the middle temporal gyrus of the dominant left
      hemisphere (LTL-N400) predicted immediate recall performance after learning,
      whereas N400s, elicited by words but not pictures in the left anterior medial
      temporal lobe (AMTL-N400), predicted delayed recall. The number of words that
      were learned but forgotten after a 30-min delay correlated only with N400s
      elicited by words in the left anterior medial temporal lobe. Thus, intracranial
      recordings indicated that different electrophysiological responses in different
      temporal lobe structures were linked to memory scores from specific
      neuropsychological tests.

PMID- 9153029
TI  - The grammatical properties of mass nouns: an aphasia case study.
AB  - A patient (F.A.) is described who, as a consequence of brain damage, shows an
      isolated deficit concerning the use, across a series of tasks, of the grammatical
      properties of mass/non-countable nouns. Her use of grammar is otherwise perfect.
      This behaviour dissociates from that of other patients who have severe
      grammatical difficulties, but do not show any impairment in the mass nouns tasks
      that F.A. fails. This case is thought to demonstrate how specific grammatical
      rules, that are said to be stored at the lemma level of lexical retrieval, are
      indeed independently represented and accessible.

PMID- 9153030
TI  - Differential impairments in recalling people's names: a case study in search of
      neuroanatomical correlates.
AB  - The case of a patient with selective left hemispheric medial and lateral temporal
      lobe damage is described. The patient was of slightly supra-average intelligence
      and had no problems in normal memory functions, but was severely anomic with
      respect to people's names. One month post-onset, this deficit held for names of
      colleagues and friends she had gotten to know during the last 10 years prior to
      the infarct and for all names confronted with post-infarct. On the other hand,
      learning of face-name associations was preserved and was independent of the
      ability to generate context-specific information for the subjects whose names
      were requested. The results support the existence of category-specific naming
      impairments, and, moreover, indicate a deficit that has to be differentiated with
      regard to memory systems. A time-limited, but prolonged engagement of
      interconnected left medial and adjacent lateral temporal lobe structures in
      ecphory is stressed for context-restricted information such as proper names.

PMID- 9153031
TI  - Perceptual asymmetries in judgements of facial attractiveness, age, gender,
      speech and expression.
AB  - Lateralization of perception of various facial attributes (age, attractiveness,
      gender, lip-reading and expression) was studied using chimaeric faces in which
      the sides of the face differed along one dimension (e.g. the left side was male
      and the right side female). Computer graphics were used to eliminate naturally
      occurring physical asymmetries (e.g. those present in the mouth during speech and
      spontaneous smiles) and obvious vertical mid-line joins in the photo-realistic
      chimaeric stimuli. Following previous studies, we found that subjects' judgements
      of gender and expression were influenced more by the left than the right side of
      the face (viewer's perspective). This left of face stimulus bias extended to
      judgements about facial attractiveness and facial age. This was not true of lip
      reading stimuli; for these stimuli subjects were influenced more by the right
      than the left side of the face. Thus using free fixation, it appears possible to
      demonstrate in normal subjects that brain processes underlying judgements of
      facial speech display different lateralization from the judgements of other
      facial dimensions.

PMID- 9153032
TI  - REM sleep dream mentation in right hemispherectomized patients.
AB  - Investigations of dream mentation in brain damaged patients have shed some light
      on the controversial issue of cerebral lateralization of dreaming. To examine
      further the relationships between brain function and dreaming, we studied REM
      sleep dream recall and content in four patients having undergone right functional
      or anatomical hemispherectomy and eight matched control subjects. Patients were
      found to have the capacity to report dreams to much the same extent as control
      subjects. Further, the patients' dream content was overall similar to that of the
      control subjects. The results provide strong evidence that dreaming is not a
      right-hemisphere function, and that the left hemisphere may be more critical for
      the generation of dreams. In addition, some characteristics of hemispherectomized
      patients' dream content (characters, smells) are consistent with the possibility
      that a history of epilepsy may influence REM sleep imagery over the long term.

PMID- 9153034
TI  - The effects of gender, menstrual phase and practice on the perceived location of
      the midsagittal plane.
AB  - Women show menstrual phase-related cognitive changes that suggest altered
      hemispheric activation for a particular task, such that they demonstrate the
      greatest lateral performance differences on prototypical left hemisphere tasks
      during the luteal phase and on prototypical right hemisphere tasks during
      menstruation. Additionally, menstrual phase may alter total cerebral
      responsiveness, such that response times and performance accuracy for many tasks
      are best during the luteal phase and most impaired during the menstrual phase. We
      evaluated the effect of menstrual phase on spatial bisection (a perceptuospatial
      task) to help further understand hormonally-mediated changes in interhemispheric
      dynamics. Healthy young adult women and men blindly pointed to their midsagittal
      plane with either hand. Women were repeatedly tested according to menstrual
      phase, and men were tested at similar intervals. The mean pointing error in the
      luteal phase differed significantly from that of all other phases and did not
      differ significantly from those of men, who pointed significantly to the left
      across test sessions. These findings suggest that, in space bisection tasks,
      women are more likely to have asymmetric hemispheric activation during the luteal
      phase than during the menstrual phase. Thus, space bisection did not resemble
      other prototypical right hemisphere behaviors. The luteal phase may have
      nonspecifically activated both hemispheres on this task instead of suppressing
      right hemisphere function, and a slight functional asymmetry favoring the right
      hemisphere may have been promoted. In addition, intermanual pointing
      discrepancies in both subject groups decreased over repeated sessions. This
      suggests that, while practice alters an internal kinesthetic reference, it does
      not influence an imaginal extrapersonal spatial reference.

PMID- 9153033
TI  - Contributions of the left and right cerebral hemispheres to line bisection.
AB  - Thirty-one right-hemisphere lesioned (RHL) patients, 11 left-hemisphere lesioned
      patients (LHL) and 10 normal controls (NC) bisected lines in three spatial
      location and four directional cuing conditions. The error direction and error
      size were analyzed as separate and combined variables. Seventy-seven percent of
      RHL patients and 45% of LHL patients made abnormally large errors in line
      bisection. Right-hemisphere lesioned patients were more sensitive to spatial
      location and directional cuing than NC subjects. In contrast, LHL patients were
      less sensitive to either condition than NCs. The error direction and error size
      emerged as dissociable components of line bisection. Right-hemisphere lesioned
      patients and NC subjects bisected lines consistently to one side of the true
      center. Left-hemisphere lesioned patients bisected lines equally often on both
      sides of the true center. Both RHL and LHL patients made larger absolute
      bisection errors than NC subjects, but the RHL patient's errors were larger than
      those of the LHL patients. We propose that the greater sensitivity of RHL
      patients to spatial location and directional cues and the directional consistency
      of their bisection errors represent contributions of the intact left cerebral
      hemisphere to line bisection. In contrast, the LHL patient's unrestrained ability
      to orient to both ends of the line reflects a contribution of the intact right
      cerebral hemisphere to line bisection. The failure of both groups to accurately
      bisect lines reflects a common visuospatial processing deficit that is more
      pronounced following RHLs than LHLs.

PMID- 9153035
TI  - A functional MRI study of mental image generation.
AB  - The neural substrates of mental image generation were investigated with
      functional MRI. Subjects listened to words under two different instructional
      conditions: to generate visual mental images of the words' referents, or to
      simply listen to each word and wait for the next word. Analyses were performed
      which directly compared the regional brain activity during each condition, with
      the goal of discovering whether mental image generation engages modality-specific
      visual areas, whether it engages primary visual cortex, and whether it recruits
      the left hemisphere to a greater extent than the right. Results revealed that
      visual association cortex, and not primary visual cortex, was engaged during the
      mental image generation condition. Left inferior temporal lobe (Brodmann's area
      37) was the most reliably and robustly activated area across subjects, had
      activity which extended superiorly into occipital association cortex (area 19).
      The results of this experiment support the hypothesis that visual mental imagery
      is a function of visual association cortex, and that image generation is
      asymmetrically localized to the left.

PMID- 9153036
TI  - Pathogenesis of subcortical visuo-spatial neglect. A HMPAO SPECT study.
AB  - The pathophysiology of neuropsychological disorders due to right deep-seated
      hemispheric lesions remains a debated point. We undertook this study to check the
      hypothesis according to which remote cortical dysfunction could be responsible
      for the occurrence of neglect. Twenty-eight patients presenting with a right
      sided subcortical stroke were studied. A neuropsychological battery of tests
      suitable for assessment of possible visuo-spatial neglect was performed as well
      as HMPAO SPECT. Neglect was observed in 15 cases out of 28. The lesion's site (at
      CT and/or MRI) did not allow discrimination between patients without neglect and
      patients with neglect. The latter however could be distinguished from the former
      by the presence of a remote decrease in cortical blood flow in the right temporo
      parietal region. By suggesting that cortical involvement is necessary for the
      occurrence of neglect, the results were interpreted according to a network
      approach in which subcortical neglect is attributed to a cortical deprivation
      from afferent input in the posterior part of the brain.

PMID- 9153038
TI  - Introduction to Wolf Creek IV Conference.
AB  - Early milestones of resuscitation research culminated in the 1950s in the
      documentation of modern external cardiovascular resuscitation (CPR) steps "ABC,"
      followed by advanced and prolonged life support. Implementation of guidelines has
      been suboptimal. Self-training of the public in life-supporting first aid,
      including CPR-ABC-available since the 1970s-is only now being re-evaluated and
      hopefully implemented. Standard external CPR potency is inadequate for reliably
      restoring spontaneous circulation and saving the brain after prolonged arrests or
      in patients with sick hearts. Ultra-advanced life-support methods such as open
      chest CPR and emergency cardiopulmonary bypass should be tried for bridging
      standard external CPR-resistant hearts to recovery or repair. Outcome studies in
      large animals can be fully controlled, in contrast to randomized clinical outcome
      trials, which have limitations. The HIV paranoia must not lead to abandoning the
      teaching of steps A and B, which are essential for any kind of coma, asphyxial
      arrest, and prolonged ventricular fibrillation arrest. Sternal compressions alone
      can produce some ventilation in animals, but not reliably in comatose humans. For
      cerebral resuscitation after cardiac arrest, the outcome benefit of the
      hypertensive bout, other cerebral blood flow-promoting measures, and mild
      resuscitative hypothermia have been documented in outcome models of large animals
      and are ready for clinical feasibility trials. The Wolf Creek CPR researchers'
      conferences I, II, and III were meant to advise the guidelines-setting committees
      of the American Heart Association and other agencies. The ten topics of Wolf
      Creek IV, published in this issue of New Horizons, were different in design and
      objective. There was an appropriate emphasis on fully automatic external
      defibrillation by lay rescuers, which has the potential for a breakthrough
      effect. Wolf Creek V, which we recommend to be conducted around the turn of the
      millennium, should focus on the pathophysiology and therapeutics of respiratory,
      cardiac, and cerebral resuscitation in general, and on organ, cellular, and
      molecular level research into how cells, organs, and organisms die, and how acute
      dying processes might be reversed. What to teach whom and how should be left to
      guideline conferences of agencies.

PMID- 9153037
TI  - Tone duration discrimination in Parkinson's disease.
AB  - Patients with Parkinson's disease (PD) and healthy controls took a computerized
      test of tone duration discrimination (TDD) using pairs of tones of 0.4-1.6 sec
      duration, presented at intervals of 0.5-4 sec. In PD patients as well as
      controls, TDD was impaired by even slight degrees of cognitive deterioration. PD
      yielded impaired TDD in females, but not in males. This suggests that the
      dopamine-powered biological clock, which is vulnerable to PD, is more important
      for the processing of durations in the 1-sec range in women than in men.

PMID- 9153039
TI  - Research on CPR: reordering priorities.
AB  - The "ABCs" of CPR, i.e., airway, breathing, and circulation, represent the
      sequence of interventions currently advised and taught to providers of both basic
      life support (BLS) and advanced life support (ALS) by the American Heart
      Association. Nevertheless, in the settings of suspected or confirmed ventricular
      fibrillation, the ABCs may be deferred such that external electrical
      countershock(s) take(s) precedence. However, efforts to restore circulation by
      chest compression (or alternative mechanical means) remain the lowest of the
      three priorities for both BLS and ALS as presently prescribed. This ordering of
      priorities is based largely on the consensus rather than objective experimental
      or clinical evidence of improved outcomes. During the last 5 yrs, both clinical
      and experimental studies demonstrated that the A and B of these ABCs, and
      specifically positive-pressure ventilation, may not be essential during the
      initial 6 to 12 mins of CPR under conditions of sudden dysrhythmic cardiac arrest
      and in the absence of asphyxia. Recent studies further suggested that either or
      both precordial compression and spontaneous gasping may of itself generate
      sufficient alveolar ventilation during the initial 6 mins of CPR. Defibrillation
      now emerges as the highest priority. Automated defibrillators have a pivotal
      role. The need for objective controlled research, including experience with
      devices in clinical settings and technical improvements of operation, are
      essential.

PMID- 9153040
TI  - Alternatives to conventional chest compression.
AB  - Alternative techniques to precordial compression are sought to improve the return
      of spontaneous circulation after cardiopulmonary arrest. The pathophysiology of
      cardiac arrest and the methods to determine the efficacy of a new technique need
      critical re-examination. Vest cardiopulmonary resuscitation (CPR), active
      compression/decompression with abdominal counterpulsation (LifeStick [Datascope,
      Fairfield, NJ]) CPR, and ascending aortic balloon inflation with saline infusion
      are promising methods that have been shown to augment coronary perfusion pressure
      and improve the return of spontaneous circulation in animals. Preliminary studies
      in human cardiopulmonary arrest have been performed with vest CPR and ascending
      aortic balloon inflation with saline infusion, with favorable hemodynamic
      results. In parallel with the development of new methods, the availability and
      adequacy of bystander CPR should be re-emphasized.

PMID- 9153041
TI  - Human research on cardiopulmonary resuscitation: current constraints on
      implementation.
AB  - Researchers face a number of constraints to human resuscitation research. To
      overcome these constraints we must first recognize them and then work to develop
      solutions. The constraints include history, which tends to create a standard-of
      care aura around practices that have not been confirmed by valid research. Until
      recently, we have lacked uniform models, nomenclature, and definitions for
      resuscitation research, though the "Utstein style" movement is doing much to
      overcome this particular constraint. We have to face several barriers that emerge
      from the very nature of human cardiopulmonary emergencies, such as its relative
      rarity, the multifactorial causes and outcomes, and its sudden, unpredictable
      nature. Good research requires appropriate levels of funding. Currently, human
      resuscitation research does not rank high on the funding priority list of our
      major funding agencies. This requires an organized approach to generate funding
      support and requires strong, coherent research proposals. Despite these
      constraints, we face many opportunities to improve survival from cardiopulmonary
      emergencies.

PMID- 9153042
TI  - Automated external defibrillators: design considerations.
AB  - Biphasic defibrillation waveforms are now the standard of care in clinical use
      for defibrillation with implantable cardioverter-defibrillators (ICDs), due to
      the superior performance demonstrated over that of comparable monophasic
      waveforms. To better understand these significantly different outcomes, ICD
      research has developed cardiac cell response models to defibrillation. Waveform
      design criteria have been derived from these first principles and have been
      applied to monophasic and biphasic waveforms to optimize their parameters. These
      principles-based design criteria have produced significant improvements over the
      current art of waveforms. Monophasic defibrillation waveforms remain the standard
      of care in clinical use for transthoracic defibrillation. Waveform design has not
      yet been influenced by the important gains made in ICD research. The limitations
      of present transthoracic waveforms may be due in part to a lack of application of
      these design principles to determine optimal waveform characteristics. To
      overcome these limitations, design principles based on cell response have
      recently been developed for external defibrillation waveforms. The transthoracic
      model incorporates elements into a cell response model that extends it to
      external defibrillation. External waveform design principles demonstrate
      reductions in capacitance, voltage, duration, and delivered energy. Therefore,
      design principles based on cardiac electrophysiology may provide a means to
      significantly reduce the energy required for safe and efficacious external
      defibrillation. Footnotes, formulae, and figures augment this presentation in
      order to clarify the defibrillation waveform theory.

PMID- 9153043
TI  - Automated external defibrillators--experiences with their use and options for
      their further development.
AB  - The purpose of this session at the Wolf Creek IV Conference was to explore future
      improvements in automatic external defibrillators (AEDs). Rather then conduct a
      general brain-storming session where any and all ideas are encouraged,
      participant comments were based on either direct personal experience or based on
      the experience of others. This article captures the comments in the words of the
      speakers. Generic improvements in AEDs such as making them smaller, lighter, less
      expensive, more reliable, and easy to use are always desired. The importance of
      data collection and analysis was stressed. Of particular concern was the
      importance of time and time interval measurements. System clock and defibrillator
      clock synchronization is desired. Concern over liability was voiced by many. The
      role of the American Heart Association was discussed by both panel members and
      members of the audience.

PMID- 9153044
TI  - Minimizing hypoxic injury during cardiac arrest.
AB  - Efforts to minimize hypoxic injury may gain insight from considering treatments
      directed at different levels of biological organization, from cellular physiology
      to societal norms. At the cellular level, it appears that cells do not actually
      die during ischemia, but rather during reperfusion or resuscitation. Free
      radicals are implicated because antioxidants reduce cell death from
      ischemia/reperfusion, but typically fail to protect when only given during
      reperfusion. In preliminary work, two synergistic antioxidants were seen to offer
      significant protection even if used only during reperfusion. These findings
      suggest some cell death may be treatable at reperfusion and antioxidants targeted
      specifically at radical generation hold promise as a future therapy. On the
      organism level, blood flow during cardiopulmonary resuscitation (CPR) may be
      improved with a new manual device that combines the advantages of active
      decompression CPR with interposed-abdominal-compression CPR; preliminary
      hemodynamic data in animals are encouraging. Possible worsening of injury in the
      postarrest period may occur from overuse of beta-agonists, excessive
      defibrillation energy, untreated hypotension, and lack of attention to intensive
      care principals. At the societal level, we have failed to provide simple
      treatments that are known to save lives, particularly basic CPR and early
      defibrillation. Bystander CPR suffers from poor quality of performance and from
      lack of initiation due to concern over disease transmission. The technology for
      rapid public defibrillation exists, yet is not commonly employed. Collectively,
      survival likelihood may be predicted with a multifactor equation which may be
      useful as we develop future therapies.

PMID- 9153045
TI  - Optimal access to- and response by-public and voluntary services, including the
      role of bystanders and family members, in cardiopulmonary resuscitation.
AB  - Victims of out-of-hospital cardiac arrest in most communities are not the
      beneficiaries of an optimal healthcare system response capable of providing
      survivors who live to hospital discharge. The public at large, including family
      members and bystander witnesses of cardiac arrest, must be expected to
      participate in this optimal response capability. The American Heart Association
      Chain of Survival defines the elements of a system capable of saving lives of
      victims of ventricular fibrillation cardiac arrest. Widespread dissemination of
      only the essential elements of life-saving steps, probably through media not yet
      used for this function, will be needed to reach the largest number of people
      possible. Emergency medical services systems need to devise innovative approaches
      to rapid provision of automated external defibrillation, in many cases no doubt
      outside the boundaries of traditional means of delivery of this intervention.
      Finally, it is likely that targeted responders among the public will be
      participants in a public access defibrillation approach to dealing with sudden
      cardiac death.

PMID- 9153046
TI  - Objective measurements for guiding initiation, sequencing, and discontinuation of
      life-support intervention.
AB  - At present, there are only a limited number of objective measures available to
      clinicians resuscitating patients from cardiac arrest. The electrocardiogram and
      end-tidal CO2 are easily applied, but the data they produce are of only limited
      utility in evaluating the efficacy of chest compression and in choosing the
      sequence of therapies. In particular, we are in need of an objective test that
      can tell us when the myocardium will defibrillate into a perfusing rhythm. The
      ventricular fibrillation waveform holds information that we have not yet begun to
      utilize. Parameters derived from power spectrum analysis, such as ventricular
      fibrillation median frequency, appear promising. Combination of both old and new
      parameters may allow us to more accurately evaluate the efficacy of therapy.

PMID- 9153047
TI  - Data collection and retrieval to document the outcomes of cardiopulmonary
      resuscitation.
AB  - In this presentation from the Wolf Creek IV Conference, the panel reviewed data
      requirements for documenting the processes and outcomes associated with the
      treatment of out-of-hospital cardiac arrest. It was recognized that this was a
      multifaceted task and that at least three areas warrant consideration: a)
      emergency medical services system management, b) monitoring and improving the
      quality of care, and c) the establishment of databases for research. There was
      complete agreement that the desired outcome is the victim's survival with intact
      neurologic function. However, the means of improving outcome, short of speedy
      initiation of treatment, were less clear. It was suggested that the Utstein
      guidelines, modified for practicability, can serve as a framework to characterize
      the arrest and to describe the temporal aspect of interventions. However, it was
      recognized that there were major deficits in understanding the importance of
      specific interventions, including their timing. Additionally, means to evaluate
      the quality of care delivered on the scene are usually wanting. The availability
      of recording electrocardiograms with accompanying voice was regarded as a major
      opportunity to better monitor the care that was delivered at the scene. Some of
      the problems incurred with cardiopulmonary resuscitation research in animals were
      discussed.

PMID- 9153048
TI  - Revising educational requirements: challenging four hours for both basic life
      support and automated external defibrillators.
AB  - The instruction of cardiopulmonary resuscitation (CPR) faces new challenges. With
      the current poor resuscitation outcomes of victims of sudden death syndrome, the
      impetus to include early defibrillation as a basic skill for laypersons imposes
      the need to simplify CPR instruction and reduce the time required to teach this
      technique. The exploration of an alternative paradigm has gained both public and
      academic interest. Some of the constraints have evolved around the urgent need to
      bring both CPR and automated external defibrillation instruction to a much larger
      population segment and at the same time reduce the time needed to accomplish this
      task. Additional debate exists with respect to maintaining the current
      traditional training methods or the use of new media such as video-based
      instruction, interactive computer-based software, and public service
      announcements. To answer any one of these questions we are tasked with having to
      objectively document not only retention and performance of learned skills, but
      the ultimate impact that any of these elements have on survival and outcome. This
      has to balance against the ongoing scourge of sudden cardiac death, which claims
      the lives of 350,000 Americans each year.

PMID- 9153049
TI  - An overview of the pharmaceutical industry.
AB  - The research-based pharmaceutical industry is a large and diverse worldwide
      employer. Rapid changes in the health care marketplace have resulted in many
      changes for the industry, including a need to streamline the drug discovery and
      development process. To address this challenge, new technologies have been
      rapidly adapted. Another result of the changing marketplace has been a rapid
      consolidation with many recent mergers and acquisitions as well as internal
      reorganizations to better support new and varied customers.

PMID- 9153050
TI  - Occupational health issues in the pharmaceutical research and development
      process.
AB  - The research and development process for bringing a new drug to market can span 8
      12 years and many testing stages, during which the number of people with the
      potential for occupational exposure to dangerous compounds and their targets
      (infectious organisms) increases. Drs. Klees and Joines carefully guide the
      reader through the R & D process, indicating potential hazards along the way.

PMID- 9153051
TI  - Secondary pharmaceuticals manufacturing.
AB  - Drs. Burling and Shah examine the second part of the pharmaceuticals
      manufacturing process, in which formulations for drug delivery are determined.
      Several types of formulations and their potentials for occupational exposure are
      reviewed.

PMID- 9153052
TI  - Establishing guidance for the handling and containment of new chemical entities
      and chemical intermediates in the pharmaceutical industry.
AB  - This information is intended to guide scientists and technicians working with
      pharmaceutical substances early in development, before occupational exposure
      levels (OELs) can be set. The focus is on determining hazard categories, or
      occupational exposure bands, which may be applied temporarily until full health
      based OEL's are in place.

PMID- 9153053
TI  - Setting occupational exposure limits for pharmaceuticals.
AB  - The active ingredients used in the pharmaceutical industry's products are
      designed to modify biological processes; thus, if not adequately controlled, they
      can place employees at risk. This chapter provides an historical look at the need
      for occupational exposure limits, as well as an overview of the limit-setting
      process.

PMID- 9153054
TI  - Industrial hygiene in the pharmaceutical industry.
AB  - This chapter addresses primary and secondary manufacturing, exposure monitoring,
      engineering controls, and personal protective equipment in the pharmaceutical
      industry. Trends affecting industrial hygiene also are examined.

PMID- 9153055
TI  - Hazard communication: challenges in the pharmaceutical industry.
AB  - Several of the major regulations mandating hazard communication programs around
      the world are reviewed and their applicability to the pharmaceutical industry is
      discussed. Regulation distinctions that are key to compliance activities are
      highlighted.

PMID- 9153056
TI  - Health hazard labeling for hazard communication in the pharmaceutical industry.
AB  - Company health and safety professionals must advise workers of the potential
      hazards of workplace chemicals. Yet it is difficult to develop one, consistent
      corporate labeling strategy for worldwide use. This chapter describes one
      company's approach to devising a corporate policy satisfying all criteria.

PMID- 9153057
TI  - Occupational toxicology: test methods and approaches for the pharmaceutical
      industry.
AB  - Occupational toxicologists consider the intended pharmacologic effects of active
      substances to be adverse and undesirable in healthy workers, because of the
      absence of any therapeutic benefit. This chapter covers testing of finished
      agents as well as intermediates and related materials for determining exposure
      routes and potential toxicity.

PMID- 9153058
TI  - Reproductive health hazards in the pharmaceutical industry.
AB  - The continual development of new compounds and the ongoing search for more potent
      drugs and new technologies in the pharmaceutical industry present a challenging
      environment for the recognition and evaluation of reproductive health hazards.
      This chapter discusses toxicology and offers an overview of the organization and
      implementation of a reproductive health program.

PMID- 9153059
TI  - Onsite clinical services in the era of managed health care.
AB  - Both the employer and employee sustain an array of costs related to illness and
      injury. Dr. Larkin discusses evolving U.S. health care delivery models and cost
      designs and presents a case study demonstrating that the provision of workplace
      health care services can substantially reduce these costs.

PMID- 9153061
TI  - Merger and acquisition medicine.
AB  - This discussion of the ramifications of corporate mergers and acquisitions for
      employees recognizes that employee adaptation to the change can be a long and
      complex process. The author describes a role the occupational physician can take
      in helping to minimize the potential adverse health impact of major
      organizational change.

PMID- 9153060
TI  - Partnering occupational medicine and the pharmaceutical business.
AB  - Drs. Levin and Powell reveal the synergism between occupational medical services
      and the pharmaceutical industry, both of which share the goal of health as a core
      business. The integration opportunities unique to a pharmaceutical company's
      occupational medicine department allow for a mutually beneficial business
      alliance.

PMID- 9153062
TI  - Occupational health nursing in the pharmaceutical industry.
AB  - The occupational health nurse's traditional role of evaluating occupational
      hazards is uniquely difficult in the pharmaceutical industry due to the
      continuous discovery of new compounds. Awareness of new chemicals and knowledge
      about their hazards are essential. The authors address these specific challenges
      as well as nurses' changing roles in industry.

PMID- 9153063
TI  - Occupational health and safety information systems in the pharmaceutical
      industry.
AB  - This chapter outlines a health and safety management system that encompasses all
      of the work environments in a pharmaceutical company, including the laboratory,
      manufacturing, sales, and corporate forces. It discusses information flow and
      integration to address physical, biological, and chemical hazards present.

PMID- 9153064
TI  - Protein kinase C: a memory kinase?

PMID- 9153065
TI  - Historical review of research on protein kinase C in learning and memory.
AB  - 1. In 1977, the discovery of a new type of kinase was reported, which turned out
      to be a receptor for phorbol esters. Thereafter, several mechanisms regulating
      PKC activity and various PKC subtypes have been discovered. 2. A role for PKC in
      synaptic plasticity and information storage has been postulated in the mid-1980s.
      An important role for PKC has since been suggested in several learning and memory
      models, in which persistent changes in the activation of PKC outlasting the
      initial stimulating event are thought to be crucial. 3. A vast number of
      experiments have further substantiated a role of PKC in learning and memory
      using, molecular genetic, behavioral, pharmacological, electrophysiological or
      immunocytochemical approaches in the late 1980s and the 1990s. PKC research of
      the past decade or so of has shown some exciting aspects of the putative role of
      PKC in synaptic plasticity and information storage. 4. The authors have provided
      highlights (Table 1) on research on PKC.

PMID- 9153066
TI  - Intracellular signal modulation: a pivotal role for protein kinase C.
AB  - 1. Protein Kinase C represents a family of Ca(2+)- and phospholipid-dependent
      enzymes which catalyzes the covalent transfer of phosphate from ATP to serine and
      threonine residues on proteins. Phosphorylation of the substrate protein induces
      a conformational change and thereby a modification of its functional properties.
      2. PKC family consists of at least twelve members, divided in three
      subgroups:classical PKCs, (alpha, beta I, beta II, gamma), new PKCs, (delta,
      epsilon, eta, theta, mu) and atypical PKCs, (zeta, lambda, iota). The three
      subgroups differ in cofactors requirements and tissue expression; these
      differences in co-activators dependency and regional distribution account for the
      differential activation profile of the various PKC isoenzymes. 3. Different
      molecules involved in the intracellular signaling network are phosphorylated "in
      vitro" and "in vivo" by PKC. Many target proteins show a preferential pattern of
      phosphorylation by the different PKC isotypes. 4. Through phosphorylation PKC
      modulates the functional activity of many different intracellular signaling
      systems which transport extracellular messages from the membrane to the nucleus.
      5. The induction of apoptotic processes by the protein kinase inhibitor
      staurosporine indicates a possible role for PKC in the modulation of the
      intracellular mechanisms leading to Programmed Cell Death. 6. Abnormalities in
      both levels and activity of PKC, recently found in some chronic neurodegenerative
      syndromes, lead to the possibility that PKC dysfunction could be involved in the
      pathogenetic mechanisms of disease.

PMID- 9153067
TI  - Receptor-mediated activation of protein kinase C in hippocampal long-term
      potentiation: facts, problems and implications.
AB  - During the last decade hippocampal long-term potentiation has become one of the
      most frequently used models to study cellular mechanisms of learning and memory.
      Receptor-mediated activation of protein kinase C is thought to be involved in LTP
      stabilisation. In the present review, 1. the molecular structure and activation
      mechanisms of PKC isoenzymes, 2. the biochemical evidences for PKC activation
      after induction of LTP using different stimulation paradigms as well as 3. the
      involvement of metabotropic glutamate receptors in PKC activation after induction
      of LTP are critically discussed.

PMID- 9153068
TI  - Protein kinase C in synaptic plasticity: changes in the in situ phosphorylation
      state of identified pre- and postsynaptic substrates.
AB  - 1. Long-term potentiation and its counterpart long-term depression are two forms
      of activity dependent synaptic plasticity, in which protein kinases and protein
      phosphatases are essential. 2. B-50/GAP-43 and RC3/neurogranin are two defined
      neuronal PKC substrates with different synaptic localization. B-50/GAP-43 is a
      presynaptic protein and RC3/neurogranin is only found at the postsynaptic site.
      Measuring their phosphorylation state in hippocampal slices, allows us to
      simultaneously monitor changes in pre- and postsynaptic PKC mediated
      phosphorylation. 3. Induction of LTP in the CA1 field of the hippocampus is
      accompanied with an increase in the in situ phosphorylation of both B-50/GAP-43
      and RC3/neurogranin, during narrow, partially overlapping, time windows. 4.
      Pharmacological data show that mGluR stimulation results in an increase in the in
      situ phosphorylation of B-50/GAP-43 and RC3/neurogranin.

PMID- 9153069
TI  - The contribution of protein kinases to plastic events in the superior colliculus.
AB  - 1. The superior colliculus (SC)/optic tectum is a multi-layered midbrain area
      that harbours representations of visual and auditory space and somatic body
      surface. The development and maintenance of these sensory maps has been shown to
      involve activity and experience-dependent mechanisms. 2. The implantation of an
      extra eye primordium into the developing forebrain of Rana pipens results in the
      formation of dually innervated tecta that would have normally be solely
      innervated by the contralateral retina. The retinal projections are arranged in
      an interdigitating pattern of alternate stripes of terminations from each retina.
      The establishment of this striped pattern requires retinal activity and depends
      on N-methyl-D-aspartate (NMDA) receptors. Manipulation of protein kinase activity
      leads to the formation of an abnormal stripe pattern. 3. Regeneration of the
      goldfish retinotectal projection, following crush of the optic nerve, occurs in
      an activity dependent manner involving NMDA receptors. Furthermore, a critical
      period exists, during which retinal activity is vital for reformation of the
      visual map. Protein kinase manipulations during this period disrupt normal
      reformation. The same manoeuvres at other time points have little effect on map
      reformation. 4. An unusual form of long-term potentiation (SC-LTP) has been
      demonstrated in the in vitro preparation of the guinea-pig SC. By stimulating the
      optic layer of the SC, a postsynaptic potentiation can be recorded in the
      superficial grey layer. The expression of SC-LTP is masked but not prevented by
      blockade of NMDA receptors. The role of protein kinases in this form of synaptic
      modification has also been studied using various manipulations and inhibitors
      with varying substrate specificity. Whereas H7, an inhibitor reputed to be
      protein kinase C specific, only masks the expression of SC-LTP, K252a which has a
      broad substrate specificity blocks the induction of SC-LTP. 5. Experience
      dependent formation of the auditory space map in the deeper layers of the SC is
      believed to be under the instruction of the visual representation in the
      superficial layers. Furthermore, a crucial period exists during which normal
      auditory and visual experience are required for successful establishment of the
      auditory map. Chronic exposure to 5-aminophosphonopentanoic acid (AP5) during
      this time prevents the formation of the map. Chronic exposure to K252a, a broad
      kinase inhibitor, over the same time period, also disrupts the formation of the
      auditory space map. 6. Taken together, these models emphasise the role of protein
      kinases in synaptic plasticity observed in the SC. Furthermore, interference with
      protein kinase activity at crucial stages of regeneration or development appears
      to disrupt the sequence of events that lead to the consolidation of SC receptive
      fields.

PMID- 9153070
TI  - Protein kinase C, learning and memory: a circular determinism between physiology
      and behaviour.
AB  - 1. In vertebrates as in invertebrates, protein kinase C appears to have a key
      role in learning and memory, probably given its involvement in synaptic
      plasticity. 2. Hippocampal PKC in mammalians is activated by learning in a large
      variety of memory tasks. However, the kind of information processed, the type of
      task, and the dynamics of learning processes all induce differential changes in
      the mode of PKC activation and in its anatomy. 3. The behaviourally induced
      changes in PKC activity are often varying in their magnitude. Inter-individual
      differences in PKC basal activity are generally correlated to the ability to
      learn. 4. Pharmacologic activation and inhibition of brain PKC shows that PKC
      activation plays an important role in cognitive function. 5. Basal PKC stores
      characterising each individual could be determined by genetic factors and
      modulated through life by individual experience. 6. The issue of PKC and memory
      relationships is reformulated through a comprehensive interactionist model which
      leads to formulating some new testable predictions.

PMID- 9153071
TI  - Learning-induced alterations in hippocampal PKC-immunoreactivity: a review and
      hypothesis of its functional significance.
AB  - 1. To localize protein kinase C (PKC) in the hippocampus, PKC activity measures,
      mRNA in situ hybridization, and [3H]phorbol ester binding techniques were used
      until in the 1980s antibodies became available for in situ immunocytochemistry.
      In the late 1980s, PKC-isoform-specific antibodies were first used to map
      hippocampal PKC at the cellular and subcellular level. The mammalian hippocampus
      contains all four Ca(2+)-dependent PKC isoforms, but the (sub)cellular
      localization is both isoform- and species-specific. 2. Hippocampally-dependent
      spatial and associative learning in rat, mice and rabbit induce an increase in
      PKC immunoreactivity (ir) in hippocampal principal cells studied 24 hours after
      the animals had learned the task. Among the four Ca(2+)-dependent PKC subtypes,
      this increase is selective for the gamma-isoform. The presence of the gamma
      isoform in dendritic spines (the most likely site for synaptic plasticity and
      information storage), in contrast to PKC alpha, beta 1, and beta 2, may underlie
      the isoform-selectivity. 3. Compared to fully trained animals, subjects halfway
      training showed intermediate levels of increased PKC gamma-ir. Poor learners that
      were not able to learn the task showed considerably less enhanced PKC gamma-ir as
      compared to good learners. 4. Associative learning induced a decrease in
      astroglial PKC beta 2 and gamma-ir in those regions where a simultaneous increase
      in neuronal PKC gamma-ir was observed. This decrease most likely reflects PKC
      down-regulation, enabling the astrocytes to maintain their K+ buffering capacity
      necessary to support neuronal activity such as accompanying learning and memory.
      5. Western blot analyses revealed that the increase in PKC gamma-ir was not due
      to an increase in total amount of PKC gamma, translocation, or the proteolytic
      generation of the fragment PKM. The increase in PKC gamma-ir must therefore
      reflect a learning-induced conformational change in the PKC gamma molecule that
      results in the exposure of the antigenic site(s). 6. Although a large number of
      hippocampal pyramidal cells display learning-induced enhancement of PKC gamma-ir
      at the 24 hours post-training time point, this does not indicate, however, that
      all synapses in these neurons are used, or that the maximal PKC signal
      transduction capacity per call has been reached. 7. The enhanced PKC gamma-ir may
      reflect a form of activated PKC, since PKC stimulation by phorbol esters (both in
      hippocampal slices and mildly aldehyde fixed sections) mimicked the increase in
      PKC gamma-ir similar as seen after learning. 8. The most likely transmitter
      systems which may have induced the altered PKC gamma-ir are acetylcholine and
      glutamate. Their contribution and interaction at the cellular level are depicted
      in a schematic circuit terminating on a CA1 pyramidal cell (Fig. 4). 9. Several
      functional roles for PKC gamma in learning and memory are discussed, and a
      hypothetical model is proposed based on an endogeneous PKC inhibitor protein that
      may explain altered antibody-binding to PKC gamma after learning (Fig. 6). 10.
      The immunocytochemical approach can contribute significantly to the ongoing
      attempts to decipher part of the cellular and biochemical mechanism of learning
      and memory. The development of ever more specific and better characterized
      antibodies reactive with different sites of proteins like PKC gamma will offer
      the necessary tools for further immunocytochemical research to help unravel
      complex brain functions.

PMID- 9153072
TI  - Biologically based artificial navigation systems: review and prospects.
AB  - Diverse theories of animal navigation aim at explaining how to determine and
      maintain a course from one place to another in the environment, although each
      presents a particular perspective with its own terminologies. These vocabularies
      sometimes overlap, but unfortunately with different meanings. This paper attempts
      to define precisely the existing concepts and terminologies, so as to describe
      comprehensively the different theories and models within the same unifying
      framework. We present navigation strategies within a four-level hierarchical
      framework based upon levels of complexity of required processing (Guidance, Place
      recognition-triggered Response, Topological navigation, Metric navigation). This
      classification is based upon what information is perceived, represented and
      processed. It contrasts with common distinctions based upon the availability of
      certain sensors or cues and rather stresses the information structure and content
      of central processors. We then review computational models of animal navigation,
      i.e. of animats. These are introduced along with the underlying conceptual basis
      in biological data drawn from behavioral and physiological experiments, with
      emphasis on theories of "spatial cognitive maps". The goal is to aid in deriving
      algorithms based upon insights into these processes, algorithms that can be
      useful both for psychobiologists and roboticists. The main observation is,
      however, that despite the fact that all reviewed models claim to have biological
      inspiration and that some of them explicitly use "Cognitive Map"-like mechanisms,
      they correspond to different levels of our proposed hierarchy and that none of
      them exhibits the main capabilities of real "Cognitive Maps"--in Tolman's sense-
      that is, a robust capacity for detour and shortcut behaviors.

PMID- 9153073
TI  - Physiological role of brain endothelin in the central autonomic control: from
      neuron to knockout mouse.
AB  - Although endothelin (ET) was discovered as a potent vascular endothelium-derived
      constricting peptide, its presumed physiological and pathophysiological roles are
      now considered much more diverse than originally though. Endothelin in the brain
      is thought to be deeply involved in the central autonomic control and consequent
      cardiorespiratory homeostasis, possibly as a neuromodulator or a hormone that
      functions locally in an autocrine/paracrine manner or widely through delivery by
      the cerebrospinal fluid (CSF). This notion is based on the following lines of
      evidence. (1) Mature ET, its precursors, converting enzymes, and receptors all
      are detected at strategic sites in the central nervous system (CNS), especially
      those controlling the autonomic functions. (2) The ET is present in the CSF at
      concentrations higher than in the plasma. (3) There is a topographical
      correspondence of ET and its receptors in the CNS. (4) The ET is released by
      primary cultures of hypothalamic neurons. (5) When ET binds to its receptors,
      intracellular calcium channels. (6) An intracerebroventricular or topical
      application of ET to CNS sites elicits a pattern of cardiorespiratory changes
      accompanied by responses of vasomotor and respiratory neurons. (7) Recently
      generated knockout mice with disrupted genes encoding ET-1 exhibited, along with
      malformations in a subset of the tissues of neural crest cell lineage,
      cardiorespiratory abnormalities including elevation of arterial pressure,
      sympathetic overactivity, and impairment of the respiratory reflex. Definitive
      evidence is expected from thorough analyses of knockout mice by applying
      conventional experimental methods.

PMID- 9153074
TI  - Stabilization of Escherichia coli isopropylmalate dehydrogenase by single amino
      acid substitution.
AB  - To determine the key position for the unusual stability of isopropylmalate
      dehydrogenase from extreme thermophiles (Thermus thermophilus and T. aquaticus),
      sequence comparisons were carried out. As a result, a motif which is
      characteristic to the thermophilic dehydrogenases was found between two highly
      conserved stretches. The sequence motif was introduced into a mesophilic
      (Escherichia coli) isopropylmalate dehydrogenase, one by one. Contrary to our
      expectation, introduction of the whole motif led the mesophilic enzyme to be more
      unstable whereas substitution of only one amino acid residue in the motif
      thermostabilized the enzyme. From the 3D structure of the enzyme, a mechanism for
      the thermostabilization is speculated.

PMID- 9153075
TI  - Modified substrate specificity of L-hydroxyisocaproate dehydrogenase derived from
      structure-based protein engineering.
AB  - L-2-Hydroxyisocaproate dehydrogenase (L-HicDH) is characterized by a broad
      substrate specificity and utilizes a wide range of 2-oxo acids branched at the C4
      atom. Modifications have been made to the sequence of the NAD(H)-dependent L
      HicDH from Lactobacillus confusus in order to define and alter the region of
      substrate specificity towards various 2-oxocarbonic acids. All variations were
      based on a 3D-structure model of the enzyme using the X-ray coordinates of the
      functionally related L-lactate dehydrogenase (L-LDH) from dogfish as a template.
      This protein displays only 23% sequence identity to L-HicDH. The active site of L
      HicDH was modelled by homology to the L-LDH based on the conservation of
      catalytically essential residues. Substitutions of the active site residues
      Gly234, Gly235, Phe236, Leu239 and Thr245 were made in order to identify their
      unique participation in substrate recognition and orientation. The kinetic
      properties of the L239A, L239M, L236V and T245A enzyme variants confirmed the
      structural model of the active site of L-HicDH. The substrates 2-oxocaproate, 2
      oxoisocaproate, phenylpyruvate, phenylglyoxylate, keto-tert-leucine and pyruvate
      were fitted into the active site of the subsequently refined model. In order to
      design dehydrogenases with an improved substrate specificity towards keto acids
      branched at C3 or C4, amino acid substitutions at positions Leu239, Phe236 and
      Thr245 were introduced and resulted in mutant enzymes with completely different
      substrate specificities. The substitution T245A resulted in a relative shift of
      substrate specificity for keto-tert-leucine of more than 17000 compared with the
      2-oxocaproate (kcat/KM). For the substrates branched at C4 a relative shift of up
      to 500 was obtained for several enzyme variants. A total of nine mutations were
      introduced and the kinetic data for the set of six substrates were determined for
      each of the resulting mutant enzymes. These were compared with those of the wild
      type enzyme and rationalized by the active site model of L-HicDH. An analysis of
      the enzyme variants provided new insight into the residues involved in substrate
      binding and residues of importance for the differences between LDHs and HicDH.
      After the protein design project was complete the X-ray structure of the enzyme
      was solved in our group. A comparison between the model and the experimental 3D
      structure proved the quality of the model. All the variants were designed,
      expressed and tested before the 3D structure became available.

PMID- 9153076
TI  - Effects of insertions and deletions in a beta-bulge region of Escherichia coli
      dihydrofolate reductase.
AB  - The role of a beta-bulge in Escherichia coli dihydrofolate reductase (DHFR) has
      been explored by a series of insertion and deletion mutations. Insertion of a
      seven amino acid sequence from a structurally equivalent 'beta-blowout' sequence
      from human DHFR destabilizes E. coli DHFR by 3.6 kcal/mol and decreases catalytic
      efficiency (kcat/K(m)) 34-fold. Deletion of F137, delta 137, the looped out
      residue in the bulge, also destabilizes E. coli DHFR by 2.8 kcal/mol but only
      decreases catalytic efficiency threefold. Concurrent deletion of F137 and
      mutation of, V136 to proline to try and maintain the strand twist associated with
      the beta-bulge decreases protein stability by 3.4 kcal/mol and decreases
      catalytic efficiency 84-fold. These insertion/deletion mutations were also
      constructed in a D27S DHFR background. The D27S mutation has been described
      previously and proposed to remove the catalytic acid from the active site. The
      delta 137 mutation partially suppresses the effect of the D27S mutation as it
      decreases the K(m) for substrate, dihydrofolate, twofold. Non-additive effects
      are observed for the insertion/deletion mutations in wild-type versus D27S DHFR
      backgrounds, consistent with structural changes.

PMID- 9153077
TI  - RNA cleavage without hydrolysis. Splitting the catalytic activities of binase
      with Asn101 and Thr101 mutations.
AB  - Members of the microbial guanyl-specific ribonuclease family catalyse the
      endonucleolytic cleavage of single-stranded RNA in a two-step reaction involving
      transesterification to form a 2',3'-cyclic phosphate and its subsequent
      hydrolysis to yield the respective 3'-phosphate. The extracellular ribonuclease
      from Bacillus intermedius (binase, RNase Bi) shares a common mechanism for RNA
      hydrolysis with mammalian RNases. Two catalytic residues in the active site of
      binase, Glu72 and His101, are thought to be involved in general acid-general base
      catalysis of RNA cleavage. Using site-directed mutagenesis, binase mutants were
      produced containing amino acid substitutions H101N and H101T and their catalytic
      properties towards RNA, poly(I), poly(A), GpC and guanosine 2',3'-cyclic
      phosphate (cGMP) substrates were studied. The engineered mutant proteins are
      active in the transesterification step which produces the 2',3'-cyclic phosphate
      species but they have lost the ability to catalyse hydrolysis of the cyclic
      phosphate to give the 3' monophosphate product.

PMID- 9153078
TI  - Effects of non-conservative changes to tyrosine 76, a key DNA binding residue of
      DNase I, on phosphodiester bond cleavage and DNA hydrolysis selectivity.
AB  - Non-conservative changes, consisting of Y76E, Y76L, Y76Q and Y76W, have been made
      to tyrosine 76, one of the key DNA binding residues in DNase I. Normally Y76
      inserts into the minor groove of DNA and makes an unusual, hydrophobic, stacking
      interaction with one of the sugars. All four mutants bind to DNA more tightly
      than the wild type, but cut it more slowly as assessed by Kunitz assays. This
      gives a rather small decrease in the specificity constants (Vmax/K(m)) for the
      hydrolysis of DNA, which is roughly paralleled by the loss of activity towards
      the non-DNA small chromophoric substrate, thymidine-3',5'-di(p
      nitrophenyl)phosphate. These non-conservative mutants, therefore, show different
      behaviour to Y76A and Y76G, studied previously [Doherty A.J., Worrall A.F. and
      Connolly B.A. (1995) J: Mol. Biol., 251, 366-377]. These two mutants both bind to
      and cut DNA poorly, resulting in large decreases in Vmax/K(m) values. However,
      they showed little reduction in rates with the chromophoric substrate. It is
      likely that the altered side chains in the non-conservative mutants are still
      able to interact productively with the DNA and contribute to the observed DNA
      distortion that is essential for efficient catalysis. However, these mutations
      disrupt the active site, most probably by interference with the hydrogen bonded
      Y76-E78-H134 triad. H134 is a critical hydrolytic residue of DNase I that is
      essential for catalysis. The DNA cleavage selectivity of the Y76E, Y76L, Y76Q and
      Y76W mutants were little altered as compared with the wild-type enzyme as
      measured using the cutting patterns of a 160 base-pair Escherichia coli Tyr T
      promoter DNA fragment. This confirms earlier observations, with Y76F, Y76A and
      Y76G, that showed that this tyrosine has little role in DNA cleavage specificity.

PMID- 9153079
TI  - Expression and epitope tagging of the membrane anchor subunit (DmsC) of
      Escherichia coli dimethyl sulfoxide reductase.
AB  - Escherichia coli dimethyl sulfoxide reductase is a heterotrimer comprising a
      catalytic subunit (DmsA), an electron transfer subunit (DmsB) and an integral
      membrane anchor subunit (DmsC). DmsC is not antigenic and the production of
      antibodies to this subunit has not been successful. We have tagged DmsC at the C
      terminus with a dystrophin-specific amino acid sequence (dysp) to which
      antibodies are readily available. We were able to use this tagging technique to
      monitor expression and localization of DmsC in E. coli and non-muscle eukaryotic
      cells. Growth properties of wild-type E. coli, strain HB101, overexpressing
      DmsC:dysp suggest that the expression of DmsC is lethal to E. coli. The lethality
      could be overcome by utilizing an E. coli F0F1 ATPase mutant as the host. Growth
      conditions of culture density, duration of induction, temperature of incubation
      after induction and media conditions were investigated to optimize DmsC:dysp
      accumulation levels. In order to alleviate the problem arising from the toxicity
      of DmsC, expression in eukaryotic tissue culture was also explored. A plasmid
      expressing DmsC:dysp was transfected into COS-1 or McA-RH777 cells. The presence
      of expressed DmsC:dysp was confirmed using specific anti-dysp antibodies and
      immunofluorescence microscopy analysis revealed that the DmsC:dysp was localized
      to the endoplasmic reticulum. Expression of DmsC:dysp did not appear to be toxic
      to the eukaryotic cells. These data suggest methodologies to overcome lethality
      problems associated with the overexpression of integral membrane proteins like
      DmsC.

PMID- 9153080
TI  - The role of apo-(a) kringle-IVs in the assembly of lipoprotein-(a).
AB  - Lipoprotein-(a) [Lp(a)] is a highly atherogenic lipoprotein with unknown
      function, consisting of a low-density lipoprotein (LDL) core and the apo(a)
      glycoprotein. The characteristic structural feature of apo(a) is the presence of
      multiple so called "kringle' repeats which are in part identical and in part
      exhibit slight sequence differences. The assembly of apo(a) and LDL, which is
      determinant for plasma Lp(a) levels, takes place extracellularly and requires
      specific structural motifs in apo(a) and apoB. Here we studied the structural
      features in apo(a) necessary for high-efficient assembly. Thirteen recombinant
      apo(a) glycoproteins, which differed in the set of kringle-IV (K-IV) motifs, were
      expressed in COS-7 cells and incubated with LDL. The rate of total and disulfide
      stabilized Lp(a) complex formation was measured by an immunochemical assay.
      Constructs containing K-IV T(type)5-T10 yielded almost 100% total and 80% stable
      complexes, respectively. Deletion or replacement of the different kringles
      revealed that K-IV T6 and T7 were responsible for the high-yield assembly and
      that K-IV T5 had an amplifying effect. Increasing the absolute number of K-IV
      repeats had an additional amplifying effect. The rate of Lp(a) assembly
      correlated strongly with the affinity of these constructs to Lys-Sepharose. Our
      results have implications for understanding the metabolism of Lp(a) and may help
      to design strategies for searching natural apo(a) mutants with aberrant plasma
      Lp(a) levels.

PMID- 9153081
TI  - Engineering a de novo designed coiled-coil heterodimerization domain for the
      rapid detection, purification and characterization of recombinantly expressed
      peptides and proteins.

PMID- 9153082
TI  - Promise: a new database of information on prosthetic centres and metal ions in
      protein active sites.

PMID- 9153083
TI  - Amino acid substitutions preserve protein folding by conserving steric and
      hydrophobicity properties.
AB  - We present a comprehensive analysis of amino acid substitution patterns (sets of
      residues in a position of a multiple alignment) and conservation of
      physicochemical properties in alignments of protein sequences. Of the one million
      possible substitution patterns, only a few hundred account for the majority of
      aligned positions. Very similar distributions of substitution patterns are
      observed in all but one of the diverse databases of multiple alignments. In these
      substitution patterns we analyzed the conservation of 511 physicochemical and
      steric amino acid properties. Highest conservation was observed in those steric
      and transfer free energy-related properties that are crucial for folding. The
      best conserved steric properties include the minimal width of the side chains and
      their interactions with other residues. Among the hydrophobicity-related
      properties, charge and those properties that provide information on propensities
      to form secondary structures or side chain conformation, appear to be better
      conserved than pure hydrophobicity measures. Physicochemical sequence analysis
      based on the most conserved properties is expected to aid searching a protein
      sequence query against a database of multiple alignments, prediction of secondary
      and tertiary structures and protein engineering.

PMID- 9153084
TI  - Three-dimensional model of sensory rhodopsin I reveals important restraints
      between the protein and the chromophore.
AB  - A structural model is constructed for the integral membrane protein, sensory
      rhodopsin I (SRI), the phototaxis receptor of the archaeon Halobacterium
      salinarium. The model is built on the template of the homologous
      bacteriorhodopsin (BR). The modeling procedure includes sequence alignment, a
      side chain rotamer search and simulated annealing by restricted molecular
      dynamics. The structure is in general agreement with previous results from
      mutagenesis experiments, chromophore substitution and room and cryogenic
      temperature spectroscopy. In particular, a residue near the beta-ionone ring of
      the retinylidene chromophore is found to be critical in maintaining the proper
      isomeric conformation of the chromophore; a layer of residues lying on the
      cytoplasmic side of the chromophore pocket is found to modulate the restraints
      around the C13 region of the chromophore, affecting the isomerizations around its
      13 = 14 bond that are important to the protein's activity. The restraints in
      these regions are more stringent in SRI than in BR. The tightened restraints are
      chiefly due to van der Waals interactions, where the attractive and repulsive
      components play separable roles. Aromatic residues account for a majority of the
      restrictive interactions. It is hypothesized that the enhanced barriers due to
      these restrictions regulate the progress of SRI's photocycle, so that it can
      couple with the phototaxis reaction chain in the bacterium. A possibility is also
      suggested that conformational changes of the protein provide the signal
      recognized by the transducer.

PMID- 9153085
TI  - Structural and functional analogy between pneumolysin and proaerolysin.
AB  - Pneumolysin and proaerolysin are bacterial toxins that form pores in host cells
      by oligomerization. We propose that they may have similar structures despite a
      poor sequence identity. The crystal structure of proaerolysin reveals a protein
      composed of four domains, arranged in the shape of an elongated comma. Electron
      microscopy of the pneumolysin monomer shows a similar arrangement of domains. The
      sequence of pneumolysin recognizes the template of proaerolysin from a library of
      protein folds. A three-dimensional model of pneumolysin has been constructed by
      the comparative approach using the structure of proaerolysin. This model,
      together with results on the activity of site-specific mutants and the positions
      of antigenic sites, has been used to propose functional roles of individual
      domains.

PMID- 9153086
TI  - Prediction of the biologically active sites in eclosion hormone from the
      silkworm, Bombyx mori.
AB  - The structure-activity relationship of eclosion hormone from the silkworm, Bombyx
      mori, was analyzed. First, the probable active residues in silkworm eclosion
      hormone and also tobacco hornworm eclosion hormone were predicted by the average
      distance map method. To examine the contributions of those residues to the
      activity of silkworm eclosion hormone, Gly-substituted mutants for those
      predicted residues were produced by site-directed mutagenesis and their
      activities were evaluated by a bioassay. Finally, Glu12, Met24 and Phe25 were
      estimated to be the crucial residues for the eclosion hormone activity. The
      possibility of the development of a blocker of an eclosion hormone receptor on
      the basis of the present work is also discussed.

PMID- 9153087
TI  - Model building of a thermolysin-like protease by mutagenesis.
AB  - The present study concerns the use of site-directed mutagenesis experiments to
      optimize a three-dimensional model of the neutral protease of Bacillus subtilis
      (NP-sub). An initial model of NP-sub was constructed using the crystal structures
      of the homologous neutral proteases of Bacillus thermoproteolyticus (thermolysin)
      and Bacillus cereus as templates. The largest portion of NP-sub could be modelled
      satisfactorily, using standard techniques, but several surface-located regions
      could only be modelled with a high degree of uncertainty. In order to make the
      model more reliable in these regions a 'model building by mutagenesis' approach
      was adopted. Mutations were designed such that their effect on thermal stability
      could indicate how their local environment should be modelled. This approach
      provided insight in the local structure of several regions in NP-sub that were
      hard to model on the basis of homology with the two known structures alone.

PMID- 9153088
TI  - Improvement of thermal stability of Streptomyces cholesterol oxidase by random
      mutagenesis and a structural interpretation.
AB  - Random mutagenesis was used to enhance the thermal stability of Streptomyces
      cholesterol oxidase. Four thermostable mutants were isolated and the following
      amino acid substitutions were identified: Ser103 to Thr (mutant S103T), Val121 to
      Ala (mutant V121A), Arg135 to His (mutant R135H) and Val145 to Glu (mutant
      V145E). The wild-type and mutant enzymes were purified and characterized. The
      properties of mutants S103T, V121A and R135H were similar to those of the wild
      type but they showed improved thermal stability. When the V145E mutation was
      introduced, the thermal stability of the enzyme was markedly increased and the
      optimum pH was desirably changed to encompass a broad range from acid to alkali.
      Analysis of multiple mutants constructed by site-directed mutagenesis showed that
      all the mutations except that of R135H had an additive influence on the other
      mutations. These mutational effects are discussed in terms of a three-dimensional
      structural model of the enzyme constructed on the basis of homology modelling.

PMID- 9153090
TI  - Income security for children.

PMID- 9153089
TI  - Stability of aspartate aminotransferase from Sulfolobus solfataricus.
AB  - Aspartate aminotransferase from Sulfolobus solfataricus (SsAspAT) is an extremely
      thermophilic and thermostable dimeric enzyme which retains its structure and
      reaches maximal activity at 100 degrees C. The structural stability of this
      protein was investigated by coupling isothermally and thermally induced
      denaturation studies to molecular modeling. Gel filtration analysis indicated
      that SsAspAT unfolds with an N2 reversible 2D mechanism. In the molecular model,
      a cluster of hydrophobic residues was shown at the interface between the subunits
      of SsAspAT and suggested this cluster as a structural feature stabilizing the
      enzyme quaternary structure. At 25 degrees C, SsAspAT is less resistant to
      guanidinium chloride-induced denaturation than the cytosolic aspartate
      aminotransferase from pig heart (cpAspAT), which was chosen as a mesophilic
      counterpart in the thermodynamic analysis since it shares with SsAspAT the two
      state unfolding mechanism. Therefore, in the case of aspartate aminotransferases,
      thermal stability does not correlate with the stability against chemical
      denaturants. Isothermal denaturation curves at 25 degrees C and melting profiles
      recorded in the presence of guanidinium chloride showed that the delta G degrees
      (H2O) at 25 degrees C of SsAspAT exceeds that of cpAspAT by roughly 15 kJ/mol;
      the parameter delta n, related to the number of binding sites for the denaturant
      differentially exposed in unfolded and folded states, is higher for SsAspAT than
      for cpAspAT; and delta Cp is lower for the thermophilic enzyme than for the
      mesophilic one by 8 kJ/K.mol. These results are indicative of a less hydrophobic
      core for SsAspAT than cpAspAT. In agreement with this, the molecular model
      predicts that some charged side chains are buried in SsAspAT and interact to form
      an H-bond/ion-pair network.

PMID- 9153091
TI  - The social worker as moral citizen: ethics in action.
AB  - Social workers today face some of the most complex ethical dilemmas in the
      history of the profession. This article presents a framework of moral citizenship
      to guide ethical social work practice. The framework includes the action
      philosophies of philosopher Hannah Arendt and Lutheran theologian Paul Tillich
      integrated with concepts of professional responsibility and the unique
      contributions of social work pioneer Charlotte Towle. Social conscience and
      social consciousness, including awareness, thinking, feeling, and action, are
      major components of the framework.

PMID- 9153092
TI  - Gender differences in attitudes toward alcohol, tobacco, and other drugs.
AB  - A number of differences exist between men and women in use patterns and risk
      factors for substance abuse. In recent years these differences have received
      increased attention; however, gender-related attitudes toward substance abuse
      need additional study. This study examines gender-related differences in beliefs
      about the causes of the abuse of alcohol, tobacco, and other drugs; the power of
      various substances of abuse; the prevalence of substance use; and the
      effectiveness of various interventions. Women were more likely to attribute
      causality to biological or environmental factors, to perceive drugs as more
      powerful, to perceive a higher incidence of substance abuse, and to believe
      prevention and treatment were more effective. Therefore, prevention, assessment,
      and treatment programs should be designed differently for women than for men.

PMID- 9153093
TI  - Measuring quality of life: a new and practical survey instrument.
AB  - Despite increasing recognition of the importance of measuring the quality of life
      (QOL) of people with severe mental illness, such assessments are seldom carried
      out because of the lack of an efficient, easy-to-use, and valid measurement
      instrument. To facilitate the gathering of QOL information from clients in
      evaluation, program improvement, or other efforts, the authors present a new
      short (24-item) self-administered questionnaire called the Quality of Life
      Questionnaire (QLQ). The questionnaire assesses subjective QOL in seven areas.
      Evidence for the reliability and validity of the QLQ is based on data gathered
      from 971 clients with serious mental illness who were receiving publicly funded
      mental health services at the time of the study. The results of a confirmatory
      factor analysis using a random split-half procedure indicated that a seven-factor
      solution fit the data well. Scores on the QLQ also correlated significantly with
      the client's functioning and satisfaction with services, providing support for
      the validity of the QLQ. The advantages of the QLQ over existing measures include
      low-cost administration and some superior psychometric properties.

PMID- 9153094
TI  - Building a neighborhood network: interorganizational collaboration to prevent
      child abuse and neglect.
AB  - Policymakers have identified the community-based human services network as a
      promising model for restructuring services in neighborhoods affected by poverty,
      but researchers have found this approach complex and difficult to implement. An
      increase in networks and partnerships among service providers suggests that
      organizations are learning to work together, yet little is known about the
      processes of their collaboration. This article reports findings from an
      organizational analysis of one interorganizational collaboration in which
      executive directors and frontline practitioners from seven agencies worked for
      five years to create, implement, and institutionalize a community-based service
      network of informal and formal family support programs to help prevent child
      abuse and neglect. This article presents a theoretical framework for
      understanding community-based networks and interorganizational collaboration and
      describes and analyzes how collaboration was used as a method to build a new
      service network, the characteristics of the network, and factors that facilitated
      the collaborative processes.

PMID- 9153095
TI  - Coping with chronic pain: assessing narrative approaches.
AB  - Individuals suffering from chronic pain are of concern to social workers because
      such pain disrupts job, family, and overall social functioning and can lead to
      depression, excessive health concerns, and withdrawal from activities. This
      article discusses a project developed to gain understanding of the experiences of
      people suffering from fibromyalgia, a chronic pain condition with no visible
      symptoms, and to test the use of narrative approaches in group work with this
      population. The study used a qualitative ethnographic approach as the primary
      method and also used some quantitative measures to assess the usefulness of the
      approach. Both qualitative and quantitative findings suggest that narrative
      approaches helped participants find their own strengths and means of coping and
      helped them find identities other than as patients.

PMID- 9153096
TI  - Caregiving and social support in two illness groups.
AB  - The authors analyzed whether spouse caregivers of people with noncognitive
      disorders such as Parkinson's disease or people with cognitive disorders such as
      Alzheimer's disease differed in their use and perception of social support
      resources. There were no differences between the groups on the Social Support
      Appraisal Scale. However, caregivers of spouses diagnosed with cognitive
      disorders were older, had fewer children, and had fewer financial resources, and
      their spouses had fewer years of formal education and more problems with
      activities of daily living. On average, caregivers of Alzheimer's patients had
      been dealing with their spouses' chronic illness for a significantly shorter
      time. Results from logistic regression analysis indicated that four variables
      distinguished Alzheimer's caregivers from Parkinson's caregivers: hours of
      assistance from family members, instrumental activities of daily living, physical
      activities of daily living, and availability of personal help in a crisis.

PMID- 9153097
TI  - Should social work clients have the right to effective treatment?
AB  - Currently, the codes of ethics developed for social workers by NASW and other
      professional associations do not suggest that clients have the right to receive
      effective, empirically validated treatment. In addition, the codes place no
      explicit emphasis on empirically validated treatments when referring to social
      work competence, education, research, supervision, or the profession as a whole.
      Does the social work client have the right to receive effective treatment when
      such interventions are known to be available? Should the NASW Code of Ethics
      include such requirements to encourage more responsible behavior on the part of
      social work practitioners? This article considers some of the issues involved in
      this debate and offers suggestions as to how codes of ethics could be modified to
      include clients' right to receive effective treatment and social workers'
      obligation to be educated about and to provide such treatment.

PMID- 9153098
TI  - Single dose of betamethasone in combined medical treatment of secretory otitis
      media.
AB  - With the objective of evaluating the efficacy of cefixime and the combination of
      cefixime and betamethasone in the treatment of secretory otitis media (SOM), we
      enrolled 142 children 2 to 12 years old in a randomized, double-blind, placebo
      controlled study. All children suffered from SOM, verified by otomicroscopy and
      tympanometry, of at least 3 months' duration. Active treatment was a 10-day
      course of cefixime with and without a single dose of 6 mg betamethasone. On
      hundred forty children were available for efficacy evaluation 14 to 23 days after
      the start of treatment. A statistically significant treatment effect was found in
      the group treated with cefixime plus betamethasone (n = 59), with a 44.1% cure
      rate as compared to 19.7% in the cefixime-treated group (n = 61; p < .005) and 5%
      in the placebo group (n = 20; p < .005). Relapse rates were high and no
      statistically differences between groups remained at last valid visit. Adverse
      events possibly or probably associated with active treatment were reported in 11
      cases (9.2%). One patient reported a severe adverse event. No serious events
      occurred. The study did not show any significant long-term effect of cefixime
      treatment or any long-term treatment benefit with the addition of betamethasone
      to the antibiotic.

PMID- 9153099
TI  - Cricohyoidoepiglottopexy for glottic carcinoma with fixation or impaired motion
      of the true vocal cord: 5-year oncologic results with 112 patients.
AB  - The medical charts and operative files of 112 patients (combined inception
      cohort) with well to moderately differentiated invasive glottic squamous cell
      carcinoma presenting fixation (22) or impaired motion (90) of the true vocal cord
      (TVC) consecutively treated with cricohyoidoepiglottopexy (CHEP) at our
      institutions from 1972 to 1989 were retrospectively reviewed. A minimum 5-year
      follow-up was always achieved. The Kaplan-Meier 5-year actuarial survival, local
      recurrence, nodal recurrence, distant metastasis, and metachronous second primary
      tumor estimate for the entire group of patients were 84.7%, 5.4%, 6.4%, 1.2%, and
      10.8%, respectively. The 5-year absolute and cause-specific survival rates were
      85.5% and 94.1% for patients with fixation of the TVC and 81.3% and 96% for
      patients with impaired motion of the TVC. The 5-year actuarial local control
      rates for patients with fixation or impaired motion of the TVC were 95.4% and
      94.4%, respectively. Local recurrence was statistically more likely in patients
      with positive margins (p = .007). Nodal recurrence was statistically more likely
      in patients with local recurrence (p = .005). Permanent tracheostomy related to
      postoperative laryngeal stenosis was requested in 2 patients. Aspiration-related
      completion total laryngectomy and/or permanent gastrostomy were never requested.
      Overall, local control and laryngeal preservation were achieved in 97.3%, and
      95.5% of patients, respectively. At our institutions, the change from the
      conservative treatment modalities of radiotherapy and vertical partial
      laryngectomy to CHEP has brought about an increase in long-term survival, local
      control, and laryngeal preservation rates when compared to historical controls
      using vertical partial laryngectomy or radiotherapy.

PMID- 9153100
TI  - Lower cranial nerve schwannomas involving the jugular foramen.
AB  - Schwannomas involving the jugular foramen are rare lesions, and no consensus
      exists on their management. This paper reports on 20 such cases treated in our
      centers. Nineteen cases were operated on for removal of the tumors, and the
      remaining case is being managed by watchful expectancy. Fifteen cases were
      operated on by the petro-occipital trans-sigmoid approach with or without
      labyrinthectomy, 2 by the infratemporal fossa approach, 1 by the modified
      transcochlear approach, and 1 by the jugulo-petrosectomy approach. The petro
      occipital trans-sigmoid approach allowed single-stage, total tumor removal with
      preservation of the facial nerve and of middle and inner ear functions. Lower
      cranial nerve paralysis was the major complication and seemed to be inherent to
      the disease rather than to the approach used. No cerebrospinal fluid leak or
      meningitis occurred in the present series. So far, no recurrence has been
      detected.

PMID- 9153101
TI  - Peculiar snoring in patients with multiple system atrophy: its sound source,
      acoustic characteristics, and diagnostic significance.
AB  - It is known that abductor paralysis (AP) of the vocal folds sometimes occurs in
      patients with multiple system atrophy (MSA), and some of them have sleep apnea
      and loud snoring during sleep. However, the site of obstruction and the sound
      source of the snoring are still unknown. We performed fiberscopic examinations
      under diazepam sedation in 8 MSA patients with AP and analyzed the snoring sound.
      We found that the peculiar snoring occurred with inspiratory vibration of the
      vocal folds, and there was no obstruction in this portion. Acoustic analysis
      showed that the fundamental frequency of vocal fold snoring was 260 to 330 Hz,
      which is different from that of ordinary soft palate snoring. Recognition of
      vocal fold snoring is important in the early diagnosis of MSA and sleep-related
      breathing disorders.

PMID- 9153102
TI  - Effect of adult-onset deafness on the human central auditory system.
AB  - Degenerative change in the central auditory system was assessed in seven subjects
      with profound bilateral adult-onset deafness. The degree of transneuronal atrophy
      was determined by measuring cell size at three levels of the brain stem auditory
      pathway (anteroventral cochlear nucleus, medial superior olivary nucleus, and
      inferior colliculus). Within subjects, the relative degree of cell shrinkage was
      similar across all levels of the central pathway. Across subjects, the best
      neuronal preservation was seen in a case of viral labyrinthitis with 1 year of
      bilateral dearness and a near-normal population of cochlear ganglion cells.
      Reduction in cell size was greatest in cases of bacterial labyrinthitis or
      Scheibe degeneration with reduced populations of ganglion cells and longer
      periods of deafness. At the level of the cochlear nucleus, there was no
      consistent difference in cell size between the side stimulated by a functioning
      prosthetic device and the nonstimulated side.

PMID- 9153103
TI  - Reversible uremic deafness: is it correlated with the degree of anemia?
AB  - Hearing loss is a common finding in patients with end-stage renal failure. Uremic
      toxins, ototoxins, and axonal uremic neuropathy appear to be likely pathogenic
      factors. We analyzed whether an improvement in hearing capacity can be achieved
      with an improvement of anemia by erythropoietin (EPO) administration. Fifty
      patients on long-term hemodialysis in a single center were examined
      audiologically by otoscopy, tympanometry, pure tone audiometry, and the short
      increment sensitivity index. Twenty-five patients were treated with EPO in a dose
      of 120 U/kg per week over a period of 5 to 8 months, and the remaining 25
      patients were not treated with EPO (controls). Both groups were reexamined
      audiologically after the study period, and the results were compared. In the
      group treated with EPO, the hemoglobin level increased from 7 +/- 0.9 to 11 +/-
      0.8 g/dL, as against the control group, whose hemoglobin increased from 7.1 +/-
      0.9 to 8 +/- g/dL. The audiologic tests were repeated at the end of the study
      period, and a significant improvement of hearing was found in the patients
      treated with EPO as compared with the control group (p < .001). Our study
      suggests that improvement of anemia in patients on long-term hemodialysis by
      administration of EPO is associated with an improvement in hearing capacity in a
      significant number of patients. Thus, anemia seems to be an important factor
      responsible for hearing disorders in patients with end-stage renal failure.
      Studies with larger numbers of patients are required to confirm this observation.

PMID- 9153104
TI  - Horseradish peroxidase permeation from the capillaries of the stria vascularis
      after inoculation of endotoxin into the middle ear.
AB  - Escherichia coli-derived endotoxin was inoculated in the middle ear of guinea
      pigs 24 hours after being injected intraperitoneally. Twenty-four hours after the
      middle ear inoculation, horseradish peroxidase (HRP) was injected via the femoral
      vein and the permeability of HRP through the capillaries of the stria vascularis
      and the destination of the leaked HRP were examined. A large amount of HRP leaked
      out of the capillary through he opened endothelial cell junctions and penetrated
      the enlarged intercellular spaces. Leaked HRP entered the pinocytotic vesicles of
      the intermediate cells. Even slightly degenerated intermediate cells retained
      this function. The HRP penetrated the spongelike structure of the marginal cells
      leading to the intercellular space. This structure was not observed without
      endotoxin. The HRP could not pass the cochlear duct through the tight junctions
      between marginal cells. Blood sludging was observed in the strial capillaries. It
      appeared more frequently in the upper three turns than in the basal turn. The HRP
      leakage out of the capillaries was observed not only in the upper three turns but
      also in the basal turn.

PMID- 9153105
TI  - Comparison of soft tissue response in rabbits following laryngeal implantation
      with hydroxylapatite, silicone rubber, and Teflon.
AB  - This study evaluates the soft tissue response in rabbits following laryngeal
      implantation for medialization using hydroxylapatite prostheses, carved silicone
      rubber prostheses, and injectable Teflon. Sixteen rabbits underwent left
      recurrent laryngeal nerve section for denervation and laryngeal implantation with
      hydroxylapatite. At 1, 3, 6, and 12 months, 4 animals were painlessly sacrificed
      and processed for histology. Similarly, animals were implanted with carved
      silicone rubber prostheses or with Teflon injected through a flap in the thyroid
      lamina for comparison at 1, 3, and 6 months. In animals implanted with
      hydroxylapatite, histologic findings include limited acute inflammatory response,
      thin fibrous encapsulation, and osteogenesis in the region of the fenestra, with
      lamellar bone bridging the space between the implant and thyroid lamina. With
      silicone rubber prostheses, there is a limited inflammatory response and fibrous
      encapsulation of the implant without evidence of osteogenesis. Animals implanted
      with Teflon demonstrated a classic foreign body reaction with multinucleated
      giant cells, granuloma formation, and migration of Teflon into surrounding
      muscle. With respect to soft tissue response, both hydroxylapatite and silicone
      rubber are less reactive than Teflon. The osteogenesis observed in the presence
      of hydroxylapatite increases implant stability and minimizes the risk of
      migration. Conversely, the presence of bone growth may limit the reversibility of
      medialization procedures performed with hydroxylapatite.

PMID- 9153106
TI  - Investigation of the 4,000-Hertz dip by detailed audiometry.
AB  - It is well known that a 4,000-Hz dip is often observed in the initial stage of
      noise-induced hearing loss and acoustic trauma, but it does not always occur as a
      result of these causes, and quite often the cause is unknown. Pure tone
      audiograms of 159 patients (76 cases of noise-induced hearing loss, 62 cases of
      hearing loss of unknown cause, 21 cases of familial hearing loss) with a 4,000-Hz
      dip were studied by detailed audiometry to clarify this configuration. The types
      of dip were classified into 11 groups; however, the basic types are the cone
      type, bowl type, and dish type, which show the smooth line of the hearing
      threshold. There were no clear differences in dip configuration among the 3
      causes of hearing loss. It was thought that the dips displayed similar
      configurations regardless of the cause.

PMID- 9153107
TI  - Auditory epithelial migration. III: An immunohistologic study using anti-BrdU
      antibody on tympanic membrane in mouse.
AB  - A localization pattern of epidermal cells on the tympanic membrane (TM) and their
      migratory patterns were studied in mice, by means of immunohistologic technique
      using an anti-bromodeoxyuridine (BrdU) antibody. The BrdU was instilled
      intraperitoneally and the animals were painlessly sacrificed between 1 hour and
      10 days after the injection. An immunostaining technique using anti-BrdU
      antibodies was applied on whole mount TM tissues. One hour after injection, BrdU
      labeled cells were found in the handle of the malleus (HM) region and in the
      annular region of the pars tensa of the TM. Some labeled cells were observed in
      the intermediate region of the upper half of the superior quadrant, but no
      labeled cells were found in the remaining part of the intermediate region.
      Labeled cells were also evident in the pars flaccida without any particular
      pattern of distribution. As time elapsed after the injection, the labeled cells
      first appearing in the HM region had migrated laterally and inferiorly from the
      HM toward the annulus, while those in the annular region had considerably
      decreased in number. Results of the present study are the following: 1) the
      proliferation center of epidermal cells in the pars tensa is located in two
      different areas, i.e., the HM region and annular region, 2) newly generated cells
      in the HM region migrated from the HM region toward the annular region, whereas
      those in the annular region migrate from the the annular region to the external
      auditory canal, and 3) no specific generation center is located in the pars
      flaccida. On the basis of these results, we discuss the relationship between the
      site of the proliferation center of epidermal cells and their migratory patterns.

PMID- 9153108
TI  - Magnetic resonance imaging of the development of otitis media with effusion
      caused by functional obstruction of the eustachian tube.
AB  - In this study, magnetic resonance imaging (MRI) was used to define in vivo the
      effect of experimental functional obstruction of the eustachian tube (ET) on
      vascular permeability and the development of middle ear (ME) effusion. After
      collection of baseline data for ME pressure and MRI, the right tensor veli
      palatini muscle of 10 cynomolgus monkeys was injected with botulinum toxin A to
      induce ET obstruction. The left tensor veli palatini muscle was injected with
      saline in 4 monkeys. Right and left ME pressures and compliances were measured
      twice daily over a follow-up period of 36 days, and MRI scanning sessions
      including administration of a contrast agent, gadopentetate dimeglumine, were
      repeated on days 3, 6, 11, 15, 21, 29, and 36 in 6 animals and on days 15, 21,
      29, and 36 in 4 animals. Two right ears did not develop underpressures, 5
      developed persistent underpressures, and 3 developed underpressures that
      resolved. No changes in MRI parameters were noted for the ears that did not
      develop underpressures, but a progressive brightening of the ME on T2-weighted
      images, indicative of the development of inflammation and effusion, was noted for
      the others. Also, an increasing rate of transfer of the contrast agent between
      the vascular and ME compartments, indicative of increasing vascular permeability,
      was observed to track the temporal changes in ME pressure. These results support
      a causal relationship between ET dysfunction, ME underpressures, increased
      vascular permeability, and otitis media with effusion

PMID- 9153109
TI  - Prevertebral calcification masquerading as a hypopharyngeal foreign body.

PMID- 9153110
TI  - Clinicopathological consultation. Lymphoepithelial carcinoma of the larynx
      hypopharynx, and trachea.
AB  - Lymphoepithelial carcinoma of the larynx, hypopharynx, and trachea is a rare
      neoplasm composed of large, poorly differentiated, nonkeratinized cells
      intermingled with small nonneoplastic lymphocytes and plasma cells. It is
      histologically similar to its more common counterpart occurring in the
      nasopharynx. In contrast to nasopharyngeal carcinoma, most cases have not been
      associated with Epstein-Barr virus (EBV), although rare cases have been reported
      to be EBV-positive. The diagnosis often requires immunohistochemistry or electron
      microscopy for confirmation. The neoplasm seems to behave in a fashion
      reminiscent of nasopharyngeal carcinoma. Lymph node metastasis occurs in the
      majority of patients, and eventual visceral dissemination occurs in one fourth.
      Radiotherapy is the main treatment for the primary tumor and regional metastases,
      but chemotherapy is indicated for more advanced disease. The initial stage is the
      primary determinant of prognosis. Death from disease occurs in about one third of
      patients.

PMID- 9153111
TI  - Hair cell regeneration in the avian cochlea.
AB  - Hair cell regeneration in the avian cochlea was first identified 10 years ago in
      studies of hair cell loss following noise damage and aminoglycoside treatment.
      Since then, numerous studies from several laboratories have examined a broad
      spectrum of the steps involved in the regeneration process. In this paper, we
      assess these studies and what they indicate about the events and regulatory
      mechanisms that control hair cell regeneration. Moreover, we examine how these
      studies have led to a reexamination of the possibility for hair cell regeneration
      in mammalian vestibular and cochlear sensory epithelia.

PMID- 9153112
TI  - Outer hair cells: the inside story.
AB  - The neurobiology of hair cells is reviewed, including their transduction
      apparatus, the production and nature of receptor potentials, and the similarities
      and differences between inner hair cells and outer cells (OHCs). Intracellular
      recordings from hair cells in vivo are discussed. This is followed by a
      consideration of effects of OHC lesions and consequent notions about OHC
      functions. Feedback in the cochlea is then considered, and the role of OHCs as
      the feedback element is examined, along with putative means of producing the
      feedback.

PMID- 9153113
TI  - Functional asymmetries in the auditory system.
AB  - This paper describes interaural differences in a variety of listening tasks. We
      summarize both behavioral and electrophysiologic evidence that performance, in
      persons with both normal and impaired hearing, differs according to which ear is
      stimulated. The effect extends over the entire age range, but is especially
      evident in children and elderly persons. Results are presented in three area: 1)
      cued listening, 2) dichotic words and sentences, and 3) temporal resolution. Some
      possible clinical implications of functional asymmetries are discussed.

PMID- 9153114
TI  - Neurobehavioral studies of the central auditory system.
AB  - The history of ablation-behavior experimentation into the central system has led
      to conclusions not obviously derivable from knowledge of neuroanatomy or
      neurophysiology alone. 1) The ventral, and not the dorsal, acoustic stria is
      necessary and sufficient for discriminating the physical dimensions of sound. 2)
      The ventral, and not the dorsal, system is also necessary and sufficient for
      discriminations of both the azimuth and elevation of a sound source. 3) A
      functional "acoustic chiasm" is centered in the superior olivary complex,
      resulting in the neurobehavioral "representation" of each acoustic hemifield only
      in the contralateral side of the central system (despite the presence of
      ipsilateral activity). 4) The behavioral usefulness of the ipsilateral activity
      present above the superior olivary complex, the role of the entire dorsal
      acoustic system, and the role of the descending system remain unknown. The fact
      that the only clear structural-behavioral correspondence yet known is that
      between the superior olives and sound localization seems to suggest that the more
      fruitful avenues of further inquiry into the roles of the central auditory system
      might lie in the more biologic (or Darwinian) as opposed to the physical (or
      Helmholtzian) dimensions of auditory processing.

PMID- 9153115
TI  - Speech intelligibility of children with multichannel cochlear implants.
AB  - The purpose of this longitudinal study is to document improvements in speech
      intelligibility in children who have received multichannel cochlear implants, to
      compare their performance to that of a matched group of children with different
      levels of hearing loss who use conventional hearing aids. Speech intelligibility
      was measured by panels of listeners who analyzed recorded speech samples
      preimplant and at 6-month intervals following implantation. The results of this
      study demonstrate that prelingually deafened children with the Nucleus
      multichannel cochlear implant achieved significant improvements in speech
      intelligibility. By the 4.5- to 7.5-year intervals, the speech intelligibility
      exceeded 40%.

PMID- 9153116
TI  - Effects of early deafness on development of brain stem auditory neurons.
AB  - Early destruction of the otocyst (embryonic precursor of the inner ear) in chick
      embryos results in complex changes in developing central auditory pathways. In
      the cochlear nucleus angularis (NA) and nucleus magnocellularis (NM), 30% to 40%
      of the neurons die after otocyst removal, the survivors are shrunken, and some
      neurons in the NA migrate to an abnormal position in the brain stem. The
      characteristic forms of cochlear nucleus neurons develop normally in the absence
      of cochlear nerve input, however. In the nucleus laminaris (NL), development of
      normal dendritic size is dependent on a normal inner ear, but most of the highly
      specialized dendritic organization of this nucleus, which is important for low
      frequency sound localization, can develop normally in the absence of cochlear
      influences. Otocyst removal induces formation of a permanent functional aberrant
      axonal projection to the ipsilateral NM from the contralateral NM. Although these
      aberrant axons form functional glutamatergic synapses, these show immature
      functional properties, suggesting that cochlear nerve inputs are necessary for
      normal maturation of glutamate receptors on auditory neurons. Treatment of chick
      embryo for a brief period in ovo with 6-cyano-7-nitroquinoxaline-2,3-dione, a
      quinoxalinedione antagonist of the alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate-kainate subtype of glutamate receptor, completely and
      permanently prevents the neuronal loss in the NM produced by otocyst removal. The
      work reviewed has 1) identified aspects of development in central auditory
      neurons that are perturbed by profound early sensorineural loss, 2) identified
      aspects of development that appear independent of cochlear influences, and 3)
      suggested a potential chemotherapeutic approach to prevention of central neuronal
      death after early damage to the cochlea.

PMID- 9153117
TI  - Roles of GABAergic inhibition for the binaural processing of multiple sound
      sources in the inferior colliculus.
AB  - This review explores the questions of how spike trains that originate from lower
      auditory nuclei interact in the inferior colliculus to produce an output that
      synthesizes the information from all these sources. The focus is on the
      processing of interaural intensity disparities, the cues animals use to localize
      high-frequency sounds, and the roles of the lateral superior olives and the
      dorsal nucleus of the lateral lemniscus (DNLL) in shaping the binaural properties
      of their targets in the inferior colliculus. The main points advanced in this
      review are 1) that the DNLL shapes the binaural properties of many inferior
      collicular neurons, 2) that the inhibitory inputs to the DNLL allow it to act as
      a switch that can be turned on or off with appropriate acoustic stimulation, and
      3) that when two or more stimuli are presented, each from a different region of
      space, the first stimulus can switch the DNLL to its off position. The
      consequence of the initial stimulus is that stimuli that follow shortly
      thereafter cannot activate the DNLL, and thus the binaural properties of those
      collicular cells that receive inhibition from the DNLL are changed. The
      implications of this switching action are that the location of the initial signal
      is coded appropriately, whereas the coding of the location of the signal or
      signals that follow the initial signal is smeared, and consequently, those
      following signals cannot be accurately localized. In short, it is proposed that
      the DNLL plays a pivotal role in the way the locations of multiple sound sources
      are coded by the auditory system.

PMID- 9153118
TI  - Eradication of communicative disorders: preventive medicine in the 21st century.
AB  - Profound changes in our society occurring over the past few decades have resulted
      in a major shift in societal emphasis from labor to communication. The widespread
      use of personal computers has enhanced the importance of information
      communication in daily life. People with communication disorders are at
      substantial risk of underemployment and lowered quality of life. Advances in
      medical science and hearing health care have placed us on the thresholds of being
      able to correct, rather than remediate, certain types of hearing loss. The
      finding that auditory hair cells of submammalian species regenerate has
      stimulated greatly the field of auditory research. A new lexicon is required to
      describe this emerging field. Methods exist to protect against hearing loss,
      repair affected structures prior to their degeneration, promote dedifferentiation
      redifferentiation of undamaged structures into sensory cells, and, finally,
      promote regeneration of new sensory cells from precursor cells. Each of these
      processes has unique requirements, and all may be required to promote the
      restoration of hearing following damage or disease.

PMID- 9153119
TI  - Unravelling the genetics of deafness.
AB  - Hearing-impaired mouse mutants not only are good models for human hereditary
      deafness, but also are extremely useful for understanding the molecular basis of
      the cochlear defect. We describe here how we identified the gene responsible for
      the deafness and vestibular defects in the shaker-1 mouse mutant as a myosin VII
      gene. Three different mutations, all causing the same phenotype in different
      lines of mouse, were found, providing good evidence that we had, indeed, found
      the correct gene. The same gene was subsequently found to be involved in Usher's
      syndrome type 1B, which features deafness, vestibular dysfunction, and
      progressive retinitis pigmentosa. The myosin VII gene is expressed in sensory
      hair cells, but not in supporting cells or neurons. We are investigating the role
      of myosin VII in hair cell development and function. Analysis of the different
      mutant stocks suggests it has at least two functions. First it is involved in the
      development and maintenance of the stereocilia bundle. Second, it has a role in
      inner hair cell function. No evidence of retinal degeneration like that in
      Usher's syndrome has been found in the shaker-1 mutants so far studied. The
      benefits of understanding the function of the gene for families with Usher's type
      1B are discussed. This gene is the first to be identified as causing the most
      common type of disorder in human hearing impairment, neuroepithelial
      abnormalities, and suggests a new class of candidate genes for involvement in
      such defects.

PMID- 9153120
TI  - Botulinum toxin does not reverse the cortical dysfunction associated with
      writer's cramp. A PET study.
AB  - Previous H2(15)O PET activation studies on patients with idiopathic torsion
      dystonia (ITD) have shown overactive striatum and frontal accessory areas and
      underactivity of the primary motor cortex and caudal supplementary motor area
      (SMA) during volitional movement. We have now examined activation of the motor
      system in healthy control subjects and patients with writer's cramp while they
      write a stereotyped word repetitively at a paced rate before and after treatment
      with botulinum toxin to see if these patients showed a similar pattern of
      abnormalities and whether they were reversible. As in ITD, our patients with
      writer's cramp showed impaired activation of the contralateral primary motor
      cortex, but enhanced activation of frontal association cortex. Botulinum-toxin
      treatment improved writing and increased activation in parietal cortex and caudal
      SMA. This may represent either a change in movement strategy or associated
      cortical reorganization secondary to deefferentation of alpha motor neurons.
      However, botulinum toxin failed to improve the impaired activation of the primary
      motor cortex. We conclude that, while botulinum toxin is clinically effective in
      writer's cramp, it does not reverse the associated dysfunction of primary motor
      and premotor cortex.

PMID- 9153121
TI  - Postural responses to vibration of neck muscles in patients with idiopathic
      torticollis.
AB  - Vibration of the dorsal muscles of the neck, simulating lengthening, in standing
      man causes a visible forwards tilt of the body shown on posturography as a tonic
      sagittal sway deviation. According to the theory that posture is organized with
      respect to a 'body schema' this deviation is a result of an interpretation of the
      concurrent neck afferent and vestibular signals. Considering the hypothesis that
      neck afferent signals may be misinterpreted in patients with spasmodic
      torticollis (ST) causing abnormal postural responses, we recorded body sway
      induced by unilateral dorsal neck muscle vibration in 22 idiopathic ST patients
      (19 treated with botulinum toxin) during upright stance with eyes closed.
      Comparison groups were 19 normal subjects and 11 patients with bilateral loss of
      vestibular function (labyrinthine defective, LD) in whom neck afference should be
      intact. Both treated and untreated ST and LD patients had absent or diminished
      sway deviations. When sway deviation did occur, it was sagitally oriented as with
      normal subjects and unrelated to ST head turns. In most ST and LD patients, neck
      vibration induced neck extension, an effect which is observed in normal subjects
      only if the torso is retrained. The results suggest that neck proprioceptive
      input retains local postural functions in ST, however, it is relatively ignored
      in the context of the whole body postural control and spatial orientation. The
      mild disorders of vestibular function reported in torticollis patients may be due
      to an inability to calibrate vestibular signals by reference to corroborative
      signals from neck proprioception.

PMID- 9153122
TI  - The bilateral reach-to-grasp movement of Parkinson's disease subjects.
AB  - The performance of simultaneous movements is said to be disrupted in Parkinson's
      disease, yet there are some indications that this dysfunction is less evident for
      bilateral inter-limb actions, as opposed to unilateral simultaneous actions.
      Focussing specifically upon natural actions, this study uses a three-dimensional
      kinematics system (ELITE) to assess the movement kinematics of a bilateral non
      homologous reach-to-grasp action. The target device consisted of a large cylinder
      (diameter 8 cm) to which a handle (diameter 0.8 cm) was attached. The task was to
      reach and grasp the cylinder with one hand (gross grasp) while reaching to grasp
      the handle with the contralateral hand (precision grasp). Overall the results
      indicated that Parkinson's disease subjects, like controls, showed independent
      and appropriate kinematic parameterization of each limb. For example, and as a
      reflection of task precision requirements, the time taken to decelerate upon the
      item to be grasped was longer for the limb grasping the handle than for the limb
      grasping the cylinder. Subtle indications of compensatory mechanisms, in response
      to left upper limb inadequacies of Parkinson's disease subjects, were suggested
      by findings of an earlier timing of maximum hand grip aperture for the left than
      for the right hand, and adjustments to the final transport phase of the left arm
      under bilateral conditions. It is proposed that left-right hand differences are
      more evident with basal ganglia dysfunction, but that these differences are
      compensated for by CNS mechanisms so that natural non-homologous reach-to-grasp
      actions are performed in a functional, coordinated and appropriate manner.

PMID- 9153123
TI  - The motor syndrome associated with exaggerated inhibition within the primary
      motor cortex of patients with hemiparetic.
AB  - Following transcranial magnetic stimulation (TMS) at stimulation strength of 1.5
      times the resting motor threshold, a silent period (SP) of approximately 180 ms
      duration can be observed in surface EMG-registrations of tonically activated
      small hand muscles. This SP is believed to be generated cortically and can be
      prolonged in stroke patients, but it is not known whether a prolongation of the
      SP has any functional significance. In order to answer the question of whether
      enhanced cortical inhibition can contribute to pathophysiology of motor
      dysfunction we studied stroke patients with clearly prolonged SP durations in the
      first dorsal interosseus muscle (> 2 times that of the intact side), but with
      normal magnetically evoked motor potentials. Sixteen patients out of a cohort of
      174 consecutive patients presenting with acute hemiparetic stroke fulfilled the
      inclusion criteria. Serial TMS investigations were performed for up to 2 years
      post-stroke. In all patients, the SP duration decreased in parallel with clinical
      improvement. In two patients, intermittent clinical deterioration was accompanied
      by an increase in the SP duration. In four patients, in addition to a markedly
      prolonged SP duration, the phenomenon of a complete inability to initiate
      voluntary muscle activity for several seconds, following TMS, could be observed
      in a number of trials ('motor arrest'). Detailed clinical analysis revealed that,
      in addition to hemiparesis, distinct motor disturbances in patients with SP
      prolongation could be observed. These motor disturbances resembled those of motor
      neglect and were characterized by motivationally dependent under-utilization of
      the affected arm, impairment of movement initiation, inability to maintain a
      constant force level and to scale forces, and impairment of individual finger
      movements. In 12 of the 16 patients at least one additional behavioural
      manifestation of neglect was present. We suggest that in stroke patients severe
      motor dysfunction may be caused by hyperactivity of cortical inhibitory
      interneurons rather than by direct lesions of descending motor tracts. Cortical
      hyperinhibition may, in turn, result from damage to any of a number of afferent
      pathways to the motor cortex which modulate local interneuronal activity.

PMID- 9153124
TI  - Transcranial Doppler detected cerebral microembolism following carotid
      endarterectomy. High microembolic signal loads predict postoperative cerebral
      ischaemia.
AB  - Cerebral ischaemia, the most frequent serious complication of carotid
      endarterectomy (CEA), usually occurs in the early postoperative period and is
      often the result of thromboembolism. We hypothesized that the early postoperative
      detection of microembolic ultrasonic signals (MES) with transcranial Doppler
      ultrasound (TCD) may be of value in identifying patients at risk of postoperative
      cerebral ischaemia and that the MES rate may be an important determinant in risk
      prediction. Sixty-five patients undergoing CEA were studied at intervals up to 24
      h postoperatively with TCD insonation of the middle cerebral artery ipsilateral
      to the operation side. Study design was open and prospective with blinded off
      line analysis of MES counts. End-points were any focal ischaemic neurological
      deficit and/or death up to 30 days postoperatively. MES were detected in 69% of
      cases during the first hour postoperatively with counts ranging from 0 to 212
      MES/h (means 19 MES/h; SEM +2- 4.5; median 4 MES/h). In seven cases (10.8%)
      counts were > 50 MES/h. Five of these seven cases developed ischaemic
      neurological deficits in the territory of the insonated middle cerebral artery
      during the monitoring period. The positive predictive value of counts > 50 MES/h
      for cerebral ischaemia was 0.71. Frequent signals (> 50 MES/h) occur in
      approximately 10% of cases in the early postoperative phase of CEA and are
      predictive for the development of ipsilateral focal cerebral ischaemia.

PMID- 9153125
TI  - The pathogenesis of non-freezing cold nerve injury. Observations in the rat.
AB  - Non-freezing cold nerve injury is uncommon in civilian practice, but may reach
      epidemic proportions in war zones. Studied since the time of Hippocrates, its
      aetiology has remained elusive. We sought to replicate experimentally, a
      peripheral nerve cold temperature gradient, since this has been emphasized in
      clinical descriptions. Our observations, in the rat, of the vasa nervorum show
      that cold-induced intravascular aggregation is followed by a 'no-reflow'
      phenomenon which culminates in endothelial damage and delayed thrombotic
      occlusion.

PMID- 9153126
TI  - Slow sodium-dependent potential oscillations contribute to ectopic firing in
      mammalian demyelinated axons.
AB  - Ectopic action potentials can arise at regions of axonal demyelination, and are
      believed to contribute to a range of symptoms in patients with demyelinating
      conditions such as multiple sclerosis. The mechanism(s) by which the ectopic
      impulses are generated are uncertain. We have previously shown that such ectopic
      activity can result from inward potassium currents. Paradoxically, the potassium
      channel blocking agent 4-aminopyridine (4AP) can sometimes cause ectopic activity
      in demyelinating lesions. To study this phenomenon we have made intra-axonal
      recordings of ectopic activity in demyelinated axons, both in the presence and
      absence of 5 mM 4AP. 4AP promoted a pattern of firing which was observed, albeit
      less frequently, in demyelinated axons in the absence of this drug, namely trains
      of single impulses, or trains of short, high-frequency bursts of impulses. When
      recorded close to the demyelinated lesion, the impulses were generated by an
      underlying, almost sinusoidal oscillation of the membrane potential. This
      oscillation was abolished by the sodium channel blocking agent tetrodotoxin (0.1
      1 microM). We conclude that the ectopic spiking induced by 4AP is generated by
      membrane potential oscillations associated with the site of demyelination. The
      sodium-dependent current underlying these oscillations, together with the
      prolonged inward potassium currents which we have previously described, may
      contribute to the generation of ectopic discharges in a range of disorders of
      myelinated axons.

PMID- 9153127
TI  - An inflammatory, familial, inclusion body myositis with autoimmune features and a
      phenotype identical to sporadic inclusion body myositis. Studies in three
      families.
AB  - We describe the occurrence of an inflammatory inclusion body myositis in siblings
      of a single generation in three separate families. The disease in this total of
      seven patients was characterized by selective and early involvement of forearm
      and finger flexors, confirmed by MRI, and weakness of the quadriceps, triceps and
      foot extensors. Muscle biopsies in at least two members from each family showed
      endomysial inflammation, red-rimmed vacuoles, intracellular amyloid deposition
      and 15-18-nm tubulo-filaments within the vacuolated muscle fibres.
      Immunocytochemistry on serial muscle biopsy sections demonstrated an abundance of
      CD8+ cells invading non-necrotic, MHC-1-expressing muscle fibres. Immunogenetic
      studies showed the presence of the DR3 allele (DRB1*0301/0302) in all seven
      patients. The combination of the clinical, histological, immunopathological and
      immunogenetic features indicate that these patients have a disease identical to
      sporadic inclusion body myositis (s-IBM). We conclude that the classic,
      inflammatory, s-IBM can also occur in families (familial inclusion body
      myositis), in a pattern analogous to the familial occurrence of other autoimmune
      neurological diseases such as myasthenia gravis and multiple sclerosis. These
      observations strengthen the view that s-IBM behaves like other autoimmune
      diseases and has disease susceptibility linked to the DR3 allele.

PMID- 9153128
TI  - Quantitative assessments of elbow flexor muscle performance using twitch
      interpolation in post-polio patients: no evidence for deterioration.
AB  - A large number of patients previously affected by polio have symptoms, including
      increased weakness and fatigue, which are collectively known as a post-polio
      syndrome. Prospective measurements of strength and endurance using twitch
      interpolation in post-polio patients are lacking and hence the exact rate of
      decline in muscle function in these patients is not well defined. We therefore
      measured performance of the elbow flexor muscles twice, at a mean of 2.5 years
      apart in a group of selected post-polio subjects (Group A, n = 13) and matched
      control subjects (n = 11), and in a second group of unselected polio patients
      from a post-polio clinic (Group B, n = 40) at a mean of 1.7 years apart. All
      subjects performed 10 attempted maximal voluntary isometric contractions of the
      elbow flexor muscles, during which voluntary activation of the elbow flexor
      muscles was measured using a sensitive form of twitch interpolation. The first
      group of selected polio subjects (Group A) and matched control subjects also
      performed 45 min of submaximal exercise. During this time, at 5-min intervals,
      maximal voluntary force, voluntary activation and the amplitude of twitch
      responses to single and paired stimuli were measured in order to investigate
      central and peripheral components of muscle fatigue. There was no change in the
      polio patients' strength, voluntary activation or peripheral muscle endurance
      between testing sessions, despite an 80% probability of detecting a 2.5% change
      per year in these variables. The unselected group of patients from the post-polio
      clinic (Group B) showed no change in maximal voluntary strength or voluntary
      activation between the first and second test. There was an absence of decline in
      muscle performance in these polio patients over the test interval, despite a
      subjective deterioration in muscle function consistent with the 'post-polio
      syndrome'. This supports the view that symptoms of the post-polio syndrome are
      not due to a progressive neuronal dysfunction.

PMID- 9153129
TI  - Identification and sizing of the GAA trinucleotide repeat expansion of
      Friedreich's ataxia in 56 patients. Clinical and genetic correlates.
AB  - Fifty-six patients with a clinical diagnosis of Friedreich's ataxia were
      investigated for the GAA trinucleotide repeat expansion recently found within the
      gene X25 on chromosome 9. All 56 were found to be homozygous for the expansion,
      with all but two patients having alleles of differing sizes. The expansion size
      ranged from 2 to 5 kb, with normal alleles around 1.5 kb. Sizing of the single
      copy of the expansion in eight sets of parents revealed marked instability in the
      transmission of the expansion, with both increases and decreases in allele size
      seen. In Friedreich's ataxia patients there was a significant inverse correlation
      seen between the average of the two expansions sizes and age of onset of
      symptoms. The GAA repeat expansion was found in the homozygous state in atypical
      cases of Friedreich's ataxia, such as older age of onset, preservation of lower
      limb reflexes and cardiac presentations. In three families the father had onset
      of spinocerebellar ataxia as an adult, and in two the possibility of partial
      expression in heterozygote carrier fathers has been raised. More importantly, the
      history of an ataxic syndrome in a parent does not exclude the diagnosis of
      Friedreich's ataxia in the offspring, and tests for the expansion should be
      carried out. The third family with an affected father conforms to previously
      described 'pseudodominant' inheritance.

PMID- 9153130
TI  - Smooth pursuit and saccades to moving targets in blind hemifields. A comparison
      of medial occipital, lateral occipital and optic radiation lesions.
AB  - We tested smooth pursuit and saccades to targets within the contralateral
      homonymous visual field defects of 10 patients with unilateral cerebral
      hemispheric lesions. Four patients had medial occipital lesions that spared the
      putative motion area in lateral occipitotemporal cortex and the optic radiations
      proximal to this site. The other six had lesions involving this area or the
      proximal optic radiations. From current hypotheses, that surviving extra-striate
      cortex is responsible for 'blindsight', we expected that the patients with
      lesions restricted to medial occipital cortex would be more likely to have
      residual ocular motor responses to moving targets. We found, however, that these
      patients with sparing of the lateral motion area did not show significantly
      better correlations of either post-saccadic eye velocity with target velocity or
      initial saccadic amplitude with the position of the moving target, compared with
      the other six patients. With increased target velocities against a background of
      darkness, two patients had weakly positive ocular motor correlations. However, in
      one patient this finding was replicated by a normal control stimulating the
      patient's scotoma and, in the other patient, the correlation disappeared when the
      eye with a residual monocular temporal crescents was occluded. These features
      indicate an artifact from light scatter. Only one other patient demonstrated a
      consistent, but weak, correlation of ocular tracking with target motion in the
      blind region; paradoxically, this patient had a lateral occipitotemporal lesion.
      We conclude that sparing of the lateral motion area is not sufficient condition
      for residual tracking of moving targets in homonymous visual field defects, and
      may not even be necessary.

PMID- 9153131
TI  - The columnar organization of the neocortex.
AB  - The modular organization of nervous systems is a widely documented principle of
      design for both vertebrate and invertebrate brains of which the columnar
      organization of the neocortex is an example. The classical cytoarchitectural
      areas of the neocortex are composed of smaller units, local neural circuits
      repeated iteratively within each area. Modules may vary in cell type and number,
      in internal and external connectivity, and in mode of neuronal processing between
      different large entities; within any single large entity they have a basic
      similarity of internal design and operation. Modules are most commonly grouped
      into entities by sets of dominating external connections. This unifying factor is
      most obvious for the heterotypical sensory and motor areas of the neocortex.
      Columnar defining factors in homotypical areas are generated, in part, within the
      cortex itself. The set of all modules composing such an entity may be
      fractionated into different modular subsets by different extrinsic connections.
      Linkages between them and subsets in other large entities form distributed
      systems. The neighborhood relations between connected subsets of modules in
      different entities result in nested distributed systems that serve distributed
      functions. A cortical area defined in classical cytoarchitectural terms may
      belong to more than one and sometimes to several distributed systems. Columns in
      cytoarchitectural areas located at some distance from one another, but with some
      common properties, may be linked by long-range, intracortical connections.

PMID- 9153132
TI  - Case in point. Metastatic bronchogenic carcinoma.

PMID- 9153133
TI  - Autonomic failure and orthostatic hypotension.

PMID- 9153134
TI  - Nausea and malaise during treatment of coccidioidomycosis.

PMID- 9153136
TI  - The tyranny of technology.

PMID- 9153135
TI  - The tyranny of technology.

PMID- 9153137
TI  - This is proper management?

PMID- 9153138
TI  - A dazed and disoriented man found by the roadside.

PMID- 9153139
TI  - Analytical overload: an emerging syndrome.

PMID- 9153141
TI  - Charcot-Marie-Tooth disease: a gene-dosage effect.
AB  - A broad spectrum of inherited neuropathy has been traced to three myelin genes,
      yet in the two most common disorders, there is no mutated gene. Instead, a gene
      has an extra or missing copy, as part of a 1.5-megabase DNA duplication or
      deletion. Eventually, duplications may emerge as a large fraction of all
      mutations. The discoveries have implications even for acquired disorders-
      including carpal tunnel syndrome.

PMID- 9153140
TI  - Prostate disease in older men: 1. Benign hyperplasia.
AB  - Medical therapy with alpha 1-adrenergic blockers or 5 alpha-reductase inhibitors
      offers an alternative to the traditional choices of watchful waiting and surgery.
      Patients with obstructive symptoms and a small prostate appear to respond to
      treatment with an alpha 1-adrenergic blocker, while a 5 alpha-reductase inhibitor
      may be the preferred agent for a large gland.

PMID- 9153142
TI  - HIV vaccines: problems and prospects.
AB  - Several lines of evidence now argue strongly that a successful HIV vaccine does
      not need to block infection completely. It has to mimic what already occurs in a
      minority of unvaccinated individuals--namely, rapid clearance of infection or
      reduction of viral load to a level that does not produce symptoms or permit
      transmission to others. The various vaccine candidates are reviewed.

PMID- 9153143
TI  - Therapeutic options in atrial flutter and fibrillation.
AB  - Newer antiarrhythmic agents can control atrial flutter and fibrillation in many
      patients, although individual episodes may require cardioversion. Catheter
      ablation is often curative for refractory flutter. Ablation of atrial
      fibrillation is more difficult, because of its different mechanism. Surgical and
      catheter-based ablation procedures have been pioneered for fibrillation but
      remain experimental.

PMID- 9153144
TI  - Exploring the potential of DNA vaccination.
AB  - DNA vaccines offer a unique means of stimulating and enhancing the immune
      response. Subjects are vaccinated with the gene for a particular antigen rather
      than with the antigen itself--the foreign protein that elicits the response is
      made intracellularly. This new type of gene therapy may not only extend the
      limits of immunoprotection but may also provide new insight into microbiologic
      and immunologic processes.

PMID- 9153145
TI  - Bringing mind-body medicine into the mainstream.
AB  - Centuries-old concepts concerning the mind's influence on the body are being
      examined with renewed interest. As awareness of the health benefits of being able
      to voluntarily control vital aspects of the metabolic state increases, and as our
      understanding of the underlying molecular mechanisms of such control also
      increases, mind-body medicine may move further into the mainstream of Western
      medical practices.

PMID- 9153146
TI  - The many roles of the hospital-based physician.

PMID- 9153147
TI  - A real-world initiation into managed care.

PMID- 9153148
TI  - Gross hematuria in a young woman with seizures and skin lesions.

PMID- 9153149
TI  - Septicemia and suppuration in a Vietnam veteran.

PMID- 9153150
TI  - A solitary pulmonary nodule in a long-term smoker.

PMID- 9153151
TI  - Acute paraplegia in the absence of trauma.

PMID- 9153152
TI  - Case in point. Eosinophilic pneumonia.

PMID- 9153153
TI  - Case in point. Acute regurgitation due to ruptured mitral chordae tendineae.

PMID- 9153154
TI  - Differential diagnosis of Alzheimer's disease.
AB  - Accurate diagnosis of dementia is essential to provide appropriate treatment as
      well as patient and family counseling. It may be difficult to differentiate
      dementia from delirium. In addition, several features distinguish dementia from
      depression, but the two can coexist and the distinction may be uncertain.
      Dementias can be grouped into two categories: dementia that presents without
      prominent motor signs and dementia that presents with prominent motor signs.
      Dementias without prominent motor signs include Alzheimer's disease,
      frontotemporal dementia, and Creutzfeld-Jakob and other prion diseases. Dementias
      characterized at onset by prominent motor signs include dementias with Lewy
      bodies, idiopathic Parkinson's disease, progressive supranuclear palsy, cortico
      basal ganglionic degeneration, hydrocephalus, Huntington's disease, and vascular
      dementia. Routine diagnostic steps include a careful history, mental status
      screening, laboratory and imaging studies, and neuropsychologic testing. Genetic
      testing is available, but its use is controversial and raises complex ethical
      questions.

PMID- 9153156
TI  - Clinical features and pharmacologic treatment of behavioral symptoms of
      Alzheimer's disease.
AB  - Behavioral symptoms are an integral component of Alzheimer's disease (AD) and an
      important cause of failure of home care. Well-chosen pharmacologic and
      psychosocial treatments can improve many of the distressing problem behaviors
      that occur in the course of the disease and, in some cases, may delay
      institutionalization. However, controlled trials remain scarce, and prediction of
      treatment outcome for individual patients is still uncertain at best. Recent
      improvements in the characterization of behavioral syndromes in AD hold promise
      for increasing the specificity of treatment choice and the predictability of
      response. This article reviews features of the major behavioral problems
      associated with AD and evidence for the effectiveness of existing treatments. We
      argue that the origins of behavioral disturbances include both intrinsic
      neurobiological aspects of the disease and environmental provocations, and
      present an approach to treatment decision-making that respects both the
      clinician's need to intervene to reduce suffering and the limitations of current
      knowledge.

PMID- 9153155
TI  - The Neuropsychiatric Inventory: assessing psychopathology in dementia patients.
AB  - The Neuropsychiatric Inventory (NPI) was developed to assess psychopathology in
      dementia patients. It evaluates 12 neuropsychiatric disturbances common in
      dementia: delusions, hallucinations, agitation, dysphoria, anxiety, apathy,
      irritability, euphoria, disinhibition, aberrant motor behavior, night-time
      behavior disturbances, and appetite and eating abnormalities. The severity and
      frequency of each neuropsychiatric symptom are rated on the basis of scripted
      questions administered to the patient's caregiver. The NPI also assesses the
      amount of caregiver distress engendered by each of the neuropsychiatric
      disorders. A total NPI score and a total caregiver distress score are calculated,
      in addition to the scores for the individual symptom domains. Content validity,
      concurrent validity, inter-rater reliability, and test-retest reliability of the
      NPI are established. Different neurologic disorders have characteristic
      neuropsychiatric manifestations and distinctive NPI profiles. The NPI is
      sensitive to treatment effects and has demonstrated the amelioration of
      behavioral symptoms in Alzheimer's disease by cholinergic agents. The NPI is a
      useful instrument for characterizing the psychopathology of dementia syndromes,
      investigating the neurobiology of brain disorders with neuropsychiatric
      manifestations, distinguishing among different dementia syndromes, and assessing
      the efficacy of treatment.

PMID- 9153157
TI  - The family caregiver's role in Alzheimer's disease.
AB  - Family caregivers play an essential role in caring for patients with Alzheimer's
      disease (AD), but caregiving stress often leads to problems in caregivers' mental
      and physical health. Certain factors predict caregiver distress, such as the
      presence of patient behavioral problems and the nature of the caregivers' social
      supports and coping responses. Several tools are available to assess the level of
      caregiver distress: The results are useful in research as well as in the clinical
      setting, in which they can provide insight into patient problems. Caregivers
      value written information about AD. They also value support groups and respite
      services, although the effects of these interventions are commonly less dramatic
      than the effects achieved by more intensive psychosocial interventions.
      Physicians and other health care professionals are obliged to address the
      concerns of AD family caregivers because they play a crucial role in the optimal
      care of these patients.

PMID- 9153158
TI  - Alzheimer's disease: clinical implications of the apolipoprotein E genotype.
AB  - Inheritance of the apolipoprotein E (APOE = gene; apoE = protein) epsilon 4 gene
      is associated with a higher risk for development of Alzheimer's disease (AD) and
      for occurrence of this illness at a younger age. APOE gene dose and genotype
      interact with gender, ethnicity, and age to influence the probability of
      developing AD, as well as the rate of disease progression. The sensitivity and
      specificity of APOE genotyping, however, and the longer-term implications of the
      epsilon 4 allele as a susceptibility factor for AD, are not yet adequately
      understood to recommend the use of APOE genotyping in genetic counseling of
      asymptomatic family members of AD patients. Insufficient evidence also exists at
      this time to recommend APOE genotyping as an adjuvant for the differential
      diagnosis of dementia or as a possible predictor for response to drug therapy.
      These potential future clinical indications for apoE genotyping are under active
      investigation.

PMID- 9153159
TI  - The search for disease-modifying treatment for Alzheimer's disease.
AB  - As a result of advances in the understanding of neurodegenerative mechanism in
      Alzheimer's disease, several strategies for the development of disease-modifying
      treatment are being investigated. Nerve growth factor and other neurotrophins may
      improve neuronal survival, although targeted delivery remains an obstacle.
      Modulation of protein processing has the potential to decrease the formation of
      plaques and tangles. Pharmacologic reduction of oxidative stress and destructive
      inflammation may slow the rate of neurodegeneration. Continued research into
      basic mechanisms, along with therapeutic trials of promising drugs, are improving
      the likelihood that it will soon be possible to slow the progression of this
      disease.

PMID- 9153160
TI  - Genesis of Alzheimer's disease.
AB  - Our understanding of the pathogenesis of Alzheimer's disease (AD) had advanced
      rapidly, particularly in the area of genetics. Clinical trials of agents that
      offer the promise of going beyond symptomatic treatment to actually slowing the
      progression of disease, perhaps by enhancing the viability of neurons, are under
      way. Most of the ideas for therapeutic approaches that may slow progression of
      disease have come from a combination of epidemiologic and basic science
      observations. Anti-inflammatory agents, nicotine, estrogens, and free radical
      scavengers are major areas of inquiry. In addition to being a biological
      condition of considerable complexity, AD is also challenging from a social and
      cultural perspective. An appreciation of the changes occurring in our scientific
      and clinical environments may lead to building more effective bridges between
      science and society and to better diagnostic and therapeutic approaches to AD.

PMID- 9153161
TI  - Ovarian steroids and the brain: implications for cognition and aging.
AB  - Ovarian steroids have many effects on the brain throughout the lifespan,
      beginning during gestation and continuing into senescence. These hormones affect
      areas of the brain that are not primarily involved in reproduction, such as the
      basal forebrain, hippocampus, caudate putamen, midbrain raphe, and brainstem
      locus coeruleus. Here we discuss three effects of estrogens and progestins that
      are especially relevant to memory processes and identify hormonal alterations
      associated with aging and neurodegenerative diseases. First, estrogens and
      progestins regulate synaptogenesis in the CA1 region of the hippocampus during
      the 4- to 5-day estrous cycle of the female rat. Formation of new excitatory
      synapses is induced by estradiol and involves N-methyl-D-aspartate (NMDA)
      receptors, whereas synaptic downregulation involves intracellular progestin
      receptors. Second, there are developmentally programmed sex differences in the
      hippocampal structure that mat help explain why male and female rats use
      different strategies to solve spatial navigation problems. During the period of
      development when testosterone is elevated in the male, aromatase and estrogen
      receptors are transiently expressed in the hippocampus. Recent data on behavior
      and synapse induction strongly suggest that this pathway is involved in the
      masculinization or defeminization of hippocampal structure and function. Third,
      ovarian steroids have effects throughout the brain, including effects on
      brainstem and midbrain catecholaminergic neurons, midbrain serotonergic pathways,
      and the basal forebrain cholinergic system. Regulation of the serotonergic system
      appears to be linked to the presence of estrogen- and progestin-sensitive neurons
      in the midbrain raphe, whereas the ovarian steroid influence on cholinergic
      function involves induction of choline acetyltransferase and acetylcholinesterase
      according to a sexually dimorphic pattern. Because of these widespread influences
      on these various neuronal systems, it is not surprising that ovarian steroids
      produce measurable cognitive effects after ovariectomy and during aging.

PMID- 9153162
TI  - Role of estrogen in postmenopausal depression.
AB  - Estrogen has been reported to improve the cognitive functioning of postmenopausal
      women. It is suggested that estrogen replacement therapy (ERT) might be
      beneficial for improvement of mood and cognition in menopausal women. We have
      shown that this improvement is selective and is probably more apparent in complex
      integrative functions. We have also shown that estrogen can augment serotonergic
      activity as well as some norepinephrine-related processes in postmenopausal
      women. Because of its effects on mood-related neurotransmitter processes, ERT
      might decrease vulnerability to depression and be effective as an adjunct therapy
      to prevent treatment nonresponse to conventional antidepressants.

PMID- 9153163
TI  - Estrogen effects on cognition in menopausal women.
AB  - There is now considerable evidence from basic neuroscience that estrogen
      influences aspects of brain chemistry and brain morphology known to be important
      for memory functions. Prospective, controlled studies of surgically and naturally
      menopausal women demonstrated that exogenous estrogen enhanced short- and long
      term memory and the capacity for learning new associations, whereas visual memory
      was unaffected. Healthy, 65 year-old women who took estrogen also performed
      significantly better than estrogen-nonusers who were matched for age,
      socioeconomic status, and years of formal education. Finally, in 32-year-old
      women with uterine myomas, a gonadotropin-releasing hormone agonist (GnRH-a)
      resulted both in ovarian suppression and in a decrease in verbal memory which was
      reversed by addition of estrogen to the GnRH-a treatment. Taken together, these
      findings suggest that estrogen helps to maintain verbal memory and enhances the
      capacity for new learning in women, whereas other cognitive functions such as
      verbal memory are seemingly unaffected by this steroid hormone.

PMID- 9153164
TI  - The epidemiology of estrogen replacement therapy and Alzheimer's disease.
AB  - The burden of Alzheimer's disease (AD) falls more heavily on women than men. It
      is hypothesized that plummeting levels of circulating estrogens after the
      menopause increase a woman's risk for this disorder and, conversely, that
      estrogen replacement therapy may lower the risk for dementia due to AD. A number
      of estrogenic properties support the biological credibility of this hypothesis.
      Estrogen interacts with neurotrophins and neurotransmitter systems relevant to AD
      and in some model systems estrogen modulates synaptic plasticity. Effects on beta
      amyloid and apolipoprotein E may be especially germane to putative effects.
      Estrogen also may blunt neurotoxic consequences of the stress response mediated
      by the hypothalamic-pituitary-adrenal axis, augment cerebral glucose utilization,
      and enhance cerebral blood flow. Clinical studies of postmenopausal women suggest
      beneficial estrogen effects on specific cognitive skills, and small preliminary
      trials of estrogen replacement in women with AD support claims of clinical
      meaningful efficacy. Consistent with the estrogen hypothesis, cross-sectional
      studies imply that postmenopausal estrogen use could be associated with a lower
      risk for AD. Several recent epidemiologic studies in which information on
      estrogen replacement therapy was collected prospectively further support this
      contention, with a dose-response relation evident in some reports. Because
      estrogen users tend to differ from nonusers in a number of lifestyle
      characteristics, convincing demonstration of putative protective effects could
      best some from randomized, placebo-controlled, primary intervention trials. For
      the present, however, the issue of estrogen efficacy in lowering a woman's risk
      for AD remains unsettled.

PMID- 9153165
TI  - The role of estrogen in the treatment of Alzheimer's disease.
AB  - Multiple factors appear to contribute to the expression of Alzheimer's disease
      (AD). About 30 percent of cases of dementia of the Alzheimer's type can be
      attributed to genetic factors. These observations raise the possibility of
      identifying multiple interventions that may modify the disease process and,
      therefore, the clinical expression of the dementia. Prominent among factors that
      may contribute to dementia and, specifically, to dementia of the Alzheimer's type
      is cerebral vascular disease. Estrogen is a potent factor that not only prevents
      vascular disease but also improves blood flow in diseased vessels, including
      blood flow in regions on the brain affected by AD. Estrogen also has direct
      effects on neuronal function that may play an important role not only in the
      preservation of neurons but in repair of neurons damaged by disease process.
      These effects of estrogen on the CNS suggest that the hormone may be effective
      not only in the prevention of dementia but also in its treatment. The results of
      clinical trials, reviewed in this presentation, are very promising but are
      limited by the paucity of subjects and often the lack of adequate controls.
      Larger, randomized, placebo-controlled trials are needed to definitively
      establish the efficacy of estrogen in the treatment of dementia of the
      Alzheimer's type.

PMID- 9153166
TI  - Genetic susceptibility testing.

PMID- 9153167
TI  - Laparoscopic antireflux surgery for gastroesophageal reflux disease (GERD).
      Results of a Consensus Development Conference. Held at the Fourth International
      Congress of the European Association for Endoscopic Surgery (E.A.E.S.),
      Trondheim, Norway, June 21-24, 1996.
AB  - BACKGROUND: Laparoscopic antireflux surgery is currently a growing field in
      endoscopic surgery. The purpose of the Consensus Development Conference was to
      summarize the state of the art of laparoscopic antireflux operations in June
      1996. METHODS: Thirteen internationally known experts in gastroesophageal reflux
      disease were contacted by the conference organization team and asked to
      participate in a Consensus Development Conference. Selection of the experts was
      based on clinical expertise, academic activity, community influence, and
      geographical location. According to the criteria for technology assessment, the
      experts had to weigh the current evidence on the basis of published results in
      the literature. A preconsensus document was prepared and distributed by the
      conference organization team. During the E.A.E.S. conference, a consensus
      document was prepared in three phases: closed discussion in the expert group,
      public discussion during the conference, and final closed discussion by the
      experts. RESULTS: Consensus statements were achieved on various aspects of
      gastroesophageal reflux disease and current laparoscopic treatment with respect
      to indication for operation, technical details of laparoscopic procedures,
      failure of operative treatment, and complete postoperative follow-up evaluation.
      The strength of evidence in favor of laparoscopic antireflux procedures was based
      mainly on type II studies. A majority of the experts (6/10) concluded in an
      overall assessment that laparoscopic antireflux procedures were better than open
      procedures. CONCLUSIONS: Further detailed studies in the future with careful
      outcome assessment are necessary to underline the consensus that laparoscopic
      antireflux operations can be recommended.

PMID- 9153168
TI  - Postoperative immune function varies inversely with the degree of surgical trauma
      in a murine model.
AB  - BACKGROUND: Major surgery through a laparotomy incision is associated with a
      postoperative reduction in immune function. Studies in rats involving sham
      procedures suggest that immune function may be preserved after laparoscopy. This
      study investigates the effects of incision length and exposure method for bowel
      resection with respect to postoperative immune function as assessed by delayed
      type hypersensitivity (DTH) reactions. METHODS: Male Sprague Dawley rats (n =
      175) were challenged preoperatively, immediately postoperatively, and on
      postoperative day 2 with an intradermal injection of 0.2 mg phytohemagglutinin
      (PHA), a nonspecific T-cell mitogen. The averages of two measures of
      perpendicular diameters were used to calculate the area of induration. Anesthesia
      control rats underwent no procedure. Minilaparotomy rats underwent a 3.5-cm
      midline incision. Sham full laparotomy rats underwent a 7-cm midline incision.
      The open bowel-resection group underwent a cecal ligation and resection through a
      7-cm midline incision. In the laparoscopic-assisted resection group a CO2
      pneumoperitoneum and four-port technique was utilized to deliver the cecum
      through a 4-mm port where the cecum was extracorporeally ligated and resected.
      RESULTS: Preoperative responses were similar in all five groups. Incision length:
      Full laparotomy group responses were 20% smaller than anesthesia control
      responses on postoperative day (POD)1 through POD4 (p < 0.02). At no time point
      were the responses in the minilaparotomy group significantly different from
      either anesthesia control or full laparotomy group responses. Exposure method:
      The laparoscopic-assisted resection group responses were 20% larger than open
      group responses at the time of two of the four postoperative measurements (p <
      0.05, both comparisons). At all postoperative time points, open resection group
      responses were significantly smaller than control responses (p < 0.05, all
      comparisons), whereas at no time point were laparoscopic group responses
      significantly different from control responses. CONCLUSION: We conclude that
      postoperative cell-mediated immune function varies inversely with the degree of
      surgical trauma. Results from the minilaparotomy and laparoscopy groups suggest
      that procedures done through small incisions may result in preservation of
      postoperative immune function.

PMID- 9153169
TI  - Hemodynamic changes in the inferior caval vein during pneumoperitoneum. An
      experimental study in pigs.
AB  - BACKGROUND: Laparoscopic procedures of increasing difficulty and duration are
      becoming more and more common. This may cause significant challenges to the
      circulatory system and possibly influence thrombogenicity. METHODS: Experimental
      study of carbon dioxide pneumoperitoneum in pigs. RESULTS: Inferior caval vein
      blood flow remained unchanged, whereas inferior caval vein pressure increased
      during pneumoperitoneum. Inferior caval vein, pulmonary, and systemic vascular
      resistance increased during pneumoperitoneum and remained increased after
      exsufflation. CONCLUSIONS: Pneumoperitoneum leads to an increased inferior caval
      vein pressure, which could cause a dilation of peripheral veins. The similar
      patterns of vascular resistance in the inferior caval vein, pulmonary artery, and
      systemic arteries (a gradual increase remaining elevated after exsufflation)
      suggest a common humoral factor or increased sympathetic nerve activity.

PMID- 9153170
TI  - Comparison of two-dimensional vs three-dimensional camera systems in laparoscopic
      surgery.
AB  - BACKGROUND: The lack of depth perception and spatial orientation in video vision
      are the drawbacks of laparoscopic surgery. The advent of a three-dimensional
      camera system enables surgeons to regain binocular vision and may be advantageous
      in complex laparoscopic procedures. METHODS: We prospectively studied two groups
      of surgeons (with and without experiences in laparoscopic surgery) who performed
      a designated standardized laparoscopic task using a two-dimensional camera system
      (Olympus OTV-S4) vs a three-dimensional camera system (Baxter-V. Mueller VS7700)
      and compared their time performances. RESULTS: The results suggested that only
      experience in laparoscopic surgery had significant effect on individual's
      performance. We could not demonstrate any superiority of the 3D system over the
      2D system. However, two-thirds of the surgeons commented that the depth
      perception did improve. CONCLUSIONS: With further refinement of the technology,
      the 3D system may improve its potential in laparoscopic surgery.

PMID- 9153171
TI  - Laparoscopic vs conventional Nissen fundoplication. A prospective randomized
      study.
AB  - BACKGROUND: Laparoscopic Nissen fundoplication has gained wide acceptance among
      surgeons, but the results of the laparoscopic procedure have not been compared to
      the results of an open fundoplication in a randomized study. METHODS: Some 110
      consecutive patients with prolonged symptoms of grade II-IV esophagitis were
      randomized, 55 to laparoscopic (LAP) and 55 to an open (OPEN) Nissen
      fundoplication. Postoperative recovery, complications, and outcome at 3- and 12
      month follow-up were compared in the two groups. RESULTS: Five LAP operations
      were converted to open laparotomy due to esophageal perforation (two), technical
      difficulties (two), and bleeding (one). In the OPEN group (two) patients
      underwent splenectomy. There was no mortality. The mean hospital stay was 3.2
      days in the LAP group and 6.4 in the OPEN group. Dysphagia and gas bloating were
      the most common complaints 3 months after the operation in both groups. These
      symptoms had disappeared at the 12-month follow-up examination. All patients in
      the LAP group and 86% in the OPEN group were satisfied with the result.
      CONCLUSIONS: Laparoscopic Nissen fundoplication is a safe and feasible procedure.
      Complications are few and functional results are good if not better than those of
      conventional open surgery.

PMID- 9153172
TI  - Partial fundoplication for gastroesophageal reflux.
AB  - BACKGROUND: About 20% of patients with gastroesophageal reflux disease (GERD)
      have severely impaired esophageal peristalsis in addition to an incompetent lower
      esophageal sphincter. In these patients a total fundoplication corrects the
      abnormal reflux, but it is often associated with postoperative dysphagia and gas
      bloat syndrome. We studied the efficacy of partial fundoplication in such
      patients. METHODS: A partial fundoplication (240 degrees -270 degrees ) was
      performed laparoscopically in 26 patients (11 men, 15 women; mean age 50.5 years)
      with GERD (mean DeMeester score: 92 +/- 16) in whom manometry demonstrated
      severely abnormal esophageal peristalsis. RESULTS: All operations were completed
      laparoscopically and the patients were dicharged an average of 39 h after
      surgery. The preoperative symptoms resolved or improved in all patients, and no
      patient developed dysphagia or gas bloat syndrome. Postoperative pH monitoring
      showed complete or nearly complete resolution of the abnormal reflux in every
      patient. CONCLUSIONS: Partial fundoplication is an excellent treatment for
      patients with GERD and weak peristalsis, for it corrects the abnormal reflux and
      avoids postoperative dysphagia.

PMID- 9153173
TI  - Early experience with laparoscopic abdominoperineal resection.
AB  - BACKGROUND: Laparoscopic abdominoperineal resection (LAPR) has not been fully
      evaluated as a technique in the treatment of rectal and anal cancer or
      inflammatory bowel disease. The purpose of our study was to evaluate the early
      experience with laparoscopic abdominoperineal resection at Washington University
      Medical Center. METHODS: A prospective analysis was performed on the first 21
      patients undergoing the procedure at Washington University Medical Center.
      Indications for surgery included rectal cancer (14 patients), anal squamous cell
      cancer (four patients), inflammatory bowel disease (two patients), and anal
      melanoma (one patient). RESULTS: The procedure was converted to open procedure in
      four patients (19%). The mean (+/-SEM) operative time and blood loss for
      completed and converted LAPR were 239 +/- 11 min and 424 +/- 43 ml, respectively.
      Postoperative hematocrit dropped a mean of 8.3% +/- 1.2% SEM; five patients
      required blood transfusion (24%). Wound complication occurred in four patients
      (19%; three perineal, one trocar site). Bowel function returned after a mean of 3
      days, and mean postoperative hospital stay for the completed LAPR group was 5
      days. Mild pain was experienced by 81% of patients (17/21) while 19% (4/21) noted
      moderate pain, usually of the perineal wound. The mean duration of patient
      controlled analgesia use was 2 days. During the 1-44-month follow-up, six
      patients (29%) died from cancer (stage III or IV at operation) and only one
      patient developed local recurrence in the pelvis (5%). There were no trocar-site
      implants of cancer. Furthermore, there was no relationship between prior
      abdominal operations, the amount of blood loss, postoperative drop of hematocrit,
      or blood transfusion requirement and the length of hospitalization or
      complication rates. CONCLUSION: Laparoscopic abdominoperineal resection is a
      feasible alternative to the conventional open technique in both cancer and
      colitis patients.

PMID- 9153174
TI  - Abnormal cholangiograms during laparoscopic cholecystectomy. Is treatment always
      necessary?
AB  - BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) is more expensive
      and time consuming than its conventional counterpart. Therefore, it should only
      be performed when there is near certainty that stones are present. The purpose of
      this study was to identify patients who should be spared LCBDE despite an
      abnormal intraoperative cholangiogram. METHODS: Of 700 consecutive laparoscopic
      cholecystectomies performed between 1989 and 1994 by a single surgeon (R.J.F.),
      41 had abnormal intraoperative cholangiograms (6%). All 41 patients were treated
      by either immediate CBDE (19) (conventional or laparoscopic) or had postoperative
      follow-up cholangiograms (22). The patients were retrospectively assigned to one
      of three groups. Group I patients had a single "soft" indicator of
      choledocholithiasis. Group II patients had one or more of the following: (1) a
      highly suspicious abnormal intraoperative cholangiogram, (2) two or more "soft"
      indicators of choledocholithiasis, or (3) preoperative clinical findings such as
      elevated liver function studies or positive preoperative radiological studies.
      Group III patients had proven choledocholithiasis. RESULTS: In group I, there
      were 11 patients, none of whom underwent immediate CBDE. Eight of the 11 (73%)
      had normal follow-up cholangiograms due to either spontaneous stone passage or a
      false-positive intraoperative cholangiogram. There were 27 patients in group II;
      19 underwent immediate CBDE with 100% stone recovery. The remaining 8 had delayed
      treatment and in five stones were recovered, while three had normal postoperative
      cholangiograms suggesting spontaneous stone passage. In group III, all three had
      negative follow-up cholangiograms despite proven choledocholithiasis. Spontaneous
      stone passage in this group seemed highly likely. CONCLUSIONS: The finding of a
      single soft indicator results in a low rate of stone recovery postoperatively,
      and these patients should not undergo LCBDE. In this series, spontaneous stone
      passage seemed highly likely in at least 3/22 (14%) and possibly as high as 14/22
      (64%).

PMID- 9153175
TI  - Prospective evaluation of a new through-the-scope nasoduodenal enteral feeding
      tube.
AB  - BACKGROUND: With present techniques, transpyloric feeding tube placement is
      unreliable. This study evaluated a new nasoduodenal tube placed through a
      gastroscope. METHODS: A therapeutic gastroscope was advanced into the distal
      duodenum, and through the 3.7-mm channel this feeding tube was advanced under
      direct vision into the small bowel. The tube/guidewire combination was then
      advanced with the concomitant equidistant retraction of the scope until the wire
      could be grasped at the lips and exchanged to the nose using a nasal transfer
      tube. The guidewire was removed, and a "Y" connector was then attached to the end
      of the tube. RESULTS: Successful tube placement in all 21 patients (14M/7F)
      required an endoscopy time of 31 +/- 3.3 min and the tubes were utilized for 9.24
      +/- 0.94 days. Tube tips were confirmed in the distal duodenum (10) or proximal
      jejunum (11) by radiographic contrast injection. CONCLUSION: This new through-the
      scope tube can be placed in the distal duodenum quickly, safely, and
      consistently.

PMID- 9153176
TI  - Computer-based desktop system for surgical videotape editing.
AB  - BACKGROUND: The educational role of surgical video presentations should be
      optimized by linking surgical images to graphic evaluation of indications,
      techniques, and results. We describe a PC-based video production system for
      personal editing of surgical tapes, according to the objectives of each
      presentation. METHODS: The hardware requirement is a personal computer (100 MHz
      processor, 1-Gb hard disk, 16 Mb RAM) with a PC-to-TV/video transfer card plugged
      into a slot. Computer-generated numerical data, texts, and graphics are
      transformed into analog signals displayed on TV/video. A Genlock interface (a
      special interface card) synchronizes digital and analog signals, to overlay
      surgical images to electronic illustrations. The presentation is stored as
      digital information or recorded on a tape. RESULTS: The proliferation of
      multimedia tools is leading us to adapt presentations to the objectives of
      lectures and to integrate conceptual analyses with dynamic image-based
      information. We describe a system that handles both digital and analog signals,
      production being recorded on a tape. Movies may be managed in a digital
      environment, with either an "on-line" or "off-line" approach. System requirements
      are high, but handling a single device optimizes editing without incurring such
      complexity that management becomes impractical to surgeons. CONCLUSIONS: Our
      experience suggests that computerized editing allows linking surgical scientific
      and didactic messages on a single communication medium, either a videotape or a
      CD-ROM.

PMID- 9153177
TI  - Feasibility of and interest in laparoscopic assessment in recurrent urinary
      stress incontinence after Burch procedure performed by laparotomy.
AB  - BACKGROUND: The Burch colposuspension, performed by laparotomy or laparoscopy,
      remains one of the most popular operations for the treatment of genuine stress
      incontinence. The average failure rate is 10% in patients followed up for 5 years
      or more in the literature. The etiology of the failure is difficult to assess by
      clinical or urodynamic investigations; the failure may be due to weak sutures on
      the Cooper's ligaments or on the vagina, to excessive or insufficient elevation
      of the cervical neck, or to an incompetent urethral sphincter. METHODS: The
      authors performed five preperitoneal laparoscopies for recurrent urinary stress
      incontinence in women after a colposuspension performed by laparotomy in order to
      determine the etiology of the recurrence (between 1992 and 1995 at the Department
      of Gynecology of the University Hospital of Caen, France). RESULTS: Laparoscopic
      preperitoneal access was possible in all patients. No laparotomy had to be
      performed. One small bladder injury occurred during the dissection. It was
      sutured by laparoscopy. There were no postoperative complications. In one
      patient, both of the sutures had escaped. In two other patients both sutures were
      found in place, but urodynamics showed a decrease in closure pressure. In two
      other patients, complaining of dysuria (painful voiding and acute bladder
      distension) associated with urinary leakage, only the colposuspension on one side
      had failed, involving a lateral torsion of the bladder neck. CONCLUSION:
      Preperitoneal laparoscopy is feasible after a laparotomic colposuspension and
      gives a very interesting etiologic contribution to the recurrence of
      incontinence. It helps to choose the most appropriate procedure to treat these
      recurrent incontinent patients: a new colposuspension if the previous one has
      failed anatomically and a sling operation if it hasn't and if the sphincter is
      incompetent.

PMID- 9153178
TI  - Laparoscopic removal of a swallowed toothbrush.
AB  - Toothbrush swallowing is an uncommon occurrence. Unlike most cases of foreign
      body ingestion, there have been no cases of spontaneous passage reported.
      Consequently, prompt removal is recommended before complications develop. We
      report a case of toothbrush ingestion which failed attempted endoscopic removal.
      This patient was managed successfully with laparoscopic assisted removal via
      gastrotomy. We recommend this approach for the removal of any ingested foreign
      bodies when surgical intervention is indicated.

PMID- 9153180
TI  - Laparoscopic closure of esophageal perforation following pneumatic dilatation for
      achalasia. Report of two cases.
AB  - Esophageal perforation following pneumatic dilation of the esophagus is normally
      recognized shortly after the event. Two patients with esophageal perforation were
      repaired utilizing a transabdominal laparoscopic technique with suture closure of
      the perforation, contralateral Heller myotomy, and Toupet posterior partial
      fundoplication. Patients recovered excellently, were started on liquids within 3
      days of surgery, and were discharged shortly thereafter. Details of the procedure
      are presented. This minimally invasive approach is well tolerated and appropriate
      in selected patients.

PMID- 9153179
TI  - Laparoscopic transdiaphragmatic diagnostic pericardial window in the
      hemodynamically stable patient with penetrating chest trauma. A brief report.
AB  - We report two cases of laparoscopically performed transdiaphragmatic diagnostic
      pericardial window following diagnostic laparoscopy for a penetrating wound to
      the central anterior thorax below the sixth intercostal space. In the
      hemodynamically stable patient, this approach permits evaluation of the
      diaphragm, abdominal viscera, and pericardial space using a single, minimally
      invasive surgical technique.

PMID- 9153181
TI  - Laparoscopic treatment of gallbladder duplication. A plea for removal of both
      gallbladders.
AB  - BACKGROUND: Gallbladder duplication is a rare congenital condition, which can now
      be detected preoperatively by imaging studies. METHODS: We report a case of
      duplicated gallbladder with symptomatic unilobar gallstones. Appropriate biliary
      workup (ultrasound, oral cholecystography, and intravenous cholangiography)
      allowed a correct preoperative diagnosis. RESULTS: Laparoscopic treatment
      included selective removal of the diseased accessory gallbladder. However,
      postoperative acute cholecystitis and symptomatic gallstone occurred in the
      remaining main gallbladder, and laparoscopic reintervention was required 27
      months later. CONCLUSIONS: This case illustrates the need for complete removal of
      both gallbladders during initial surgery. Precise intraoperative recognition of
      vascular and biliary anatomy-including abnormalities-is highlighted to avoid
      mistakes during surgery.

PMID- 9153182
TI  - Gallbladder and cystic duct absence. An infrequent malformation in laparoscopic
      surgery.
AB  - Gallbladder absence is an infrequent anomaly normally accompanied by lack of the
      cystic duct. Of unknown etiology, in general it is accepted to be a congenital
      malformation. A male patient (age 59) diagnosed with nonfunctional symptomatic
      scleroatrophic gallbladder by echography and ERCP was operated on using a
      laparoscopic approach. Gallbladder and cystic absence was diagnosed during the
      procedure. A new case of gallbladder and cystic duct absence, diagnosed by
      laparoscopy, is presented. This type of extrahepatic bile duct malformation is
      quite rare, but it must be taken into account due to the generalization of
      laparoscopic surgery in biliar pathology because of the high risk of serious
      lesions to the hepatocholedochal system.

PMID- 9153183
TI  - Successful treatment of a rectal anastomotic stenosis by transanal endoscopic
      microsurgery (TEM) using the contact Nd:YAG laser.
AB  - We report the advantage of employing transanal endoscopic microsurgery (TEM)
      using the contact Nd:YAG laser for the treatment of a rectal anastomotic
      stenosis. A 72-year-old woman was admitted to our hospital with a postoperative
      rectal anastomotic stenosis. Twenty months prior to admission, the patient
      underwent a low anterior resection for the treatment of the rectal cancer using
      an EEA stapling device. A barium enema and colonoscopy revealed a rectal
      stenosis, 0.8-cm diameter. This stenosis was at the anastomotic site,
      approximately 4.0 from the dental line. An endoscopic treatment was performed
      transanally using the contact Nd:YAG laser. The stenotic rectal wall was
      fulgurated or vaporized completely. There were no intraoperative or postoperative
      complications. We concluded that TEM appears to be a safe and minimally invasive
      procedure. Furthermore, the contact Nd:YAG laser is very effective in treating
      the gastrointestinal stenotic area. To our knowledge, this is the first
      successful report of this novel procedure.

PMID- 9153184
TI  - A simplified approach to laparoscopic fundoplication.
AB  - BACKGROUND: There is a certain amount of controversy regarding the need to divide
      the short gastric vessels (SGV) in laparoscopic fundoplication for treatment of
      gastroesophageal reflux disease (GERD). In addition, there is often difficulty in
      identifying the crural fibers when encircling the lower esophagus. METHODS: We
      determine whether it is necessary to divide the SGV by trying to appose the
      gastric fundus to the anterior abdominal wall intraoperatively. If this could be
      done easily, the SGV are preserved. When their division is required, a posterior
      gastric approach is employed. We have also found that the injection of methylene
      blue into the left crural fibers anterior to the esophagus is helpful in
      identifying the left side when dissection posterior to the gastroesophageal
      junction is difficult. RESULTS: Between 1992 and 1995 we performed 20
      laparoscopic fundoplications for GERD. All patients had at least grade 3
      esophagitis (Savary-Miller scale), increased esophageal exposure to acid (median
      DeMeester score of 195), and decreased lower esophageal sphincter (LES) pressure.
      The median operative time was 175 min. There were no conversions to open surgery,
      and there was no mortality. Three patients developed transient postoperative
      dysphagia and one patient had pneumonia. The median hospital stay was 3 days; all
      patients were free of reflux symptoms at follow-up ranging from 7 to 42 months.
      CONCLUSION: We conclude that the techniques described by us aid in intraoperative
      decision making and allow laparoscopic fundoplication to be both simple and
      effective.

PMID- 9153185
TI  - Laparoscopic splenectomy and nephrectomy in a rat model. Description of a new
      technique.
AB  - BACKGROUND: In experimental studies on the effects of laparoscopic procedures on
      tumor biology, a localized tumor model is desirable. The spleen and the kidney
      are preferable, because these organs are amenable to tumor placement and
      subsequent removal. This study describes the technique of laparoscopic
      splenectomy and nephrectomy in the rat model. METHODS: Pneumoperitoneum was
      established by CO2 insufflation. Laparoscopic splenectomy involved two-handed
      dissection, intracorporeal ligation, and division of gastrosplenic attachments
      and hilar and short gastric vessels. Laparoscopic nephrectomy was done by
      intracorporeal ligation and division of the renal vessels and the ureter after
      mobilization of the kidney. RESULTS: Laparoscopic splenectomy was performed in
      six rats; laparoscopic nephrectomy was done in six rats. Operative time ranged
      from 45 to 90 min for splenectomy and from 40 to 65 min for nephrectomy.
      Postoperatively, two rats died from hemorrhage. Necropsy of the rats after 10
      days revealed adhesion in three rats after splenectomy and in four rats after
      nephrectomy. Inflammatory processes were found around the silk ligatures in all
      rats after splenectomy; in two rats wound infections occurred at the port sites.
      CONCLUSIONS: Laparoscopic splenectomy and nephrectomy in the rat proved
      technically feasible and may provide new localized tumor models suitable to be
      used in further studies on the oncological effects of laparoscopic surgery.

PMID- 9153186
TI  - Evidence for CPP32 activation in the absence of apoptosis during T lymphocyte
      stimulation.
AB  - Cysteine proteases of the interleukin-1beta-converting enzyme family have been
      implicated in the effector process of apoptosis in several systems. Among these,
      CPP32 has been shown to be processed to active enzyme at the onset of apoptosis.
      Here, we show that CPP32 precursor is cleaved into its active form during
      phytohaemaglutinin A activation of T lymphocytes. Maximal processing is observed
      between day 3 and day 4 following addition of mitogen and is a transient process.
      Precursor cleavage is associated with the appearance of a CPP32-like enzymatic
      activity in cell lysates. At this time in the culture, almost no apoptotic cell
      and no dead cell can be detected, and T lymphocytes are actively proliferating.
      CPP32 processing also occurs when lymphocytes are stimulated through an
      allogeneic primary mixed lymphocyte reaction. Our results suggest that
      proteolytic activation of CPP32 could be a physiological step during T lymphocyte
      activation. In addition, these data indicate that CPP32 activation can occur
      independently of programmed cell death in T lymphocytes.

PMID- 9153187
TI  - Interaction of the adaptor protein Shc and the adhesion molecule cadherin.
AB  - In mitogenic signaling pathways, Shc participates in the growth factor activation
      of Ras by interacting with activated receptors and/or the Grb-2.Sos complex.
      Using several experimental approaches we demonstrate that Shc, through its SH2
      domain, forms a complex with the cytoplasmic domain of cadherin, a transmembrane
      protein involved in the Ca2+-dependent regulation of cell-cell adhesion. This
      interaction is demonstrated in a yeast two-hybrid assay, by co-precipitation from
      mammalian cells, and by direct biochemical analysis in vitro. The Shc-cadherin
      association is phosphotyrosine-dependent and is abrogated by addition of
      epidermal growth factor to A-431 cells maintained in Ca2+-free medium, a
      condition that promotes changes in cell shape. Shc may therefore participate in
      the control of cell-cell adhesion as well as mitogenic signaling through Ras.

PMID- 9153188
TI  - Translocation of autophosphorylated calcium/calmodulin-dependent protein kinase
      II to the postsynaptic density.
AB  - Calcium/calmodulin-dependent protein kinase II (CaMKII) undergoes calcium
      dependent autophosphorylation, generating a calcium-independent form that may
      serve as a molecular substrate for memory. Here we show that calcium-independent
      CaMKII specifically binds to isolated postsynaptic densities (PSDs), leading to
      enhanced phosphorylation of many PSD proteins including the alpha-amino-3-hydroxy
      5-methyl-4-isoxazole-propionic acid (AMPA)-type glutamate receptor. Furthermore,
      binding to PSDs changes CaMKII from a substrate for protein phosphatase 2A to a
      protein phosphatase 1 substrate. Translocation of CaMKII to PSDs occurs in
      hippocampal slices following treatments that induce CaMKII autophosphorylation
      and a form of long term potentiation. Thus, synaptic activation leads to
      accumulation of autophosphorylated, activated CaMKII in the PSD. This increases
      substrate phosphorylation and affects regulation of the kinase by protein
      phosphatases, which may contribute to enhancement of synaptic strength.

PMID- 9153189
TI  - ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2
      and TRAF5.
AB  - Members of tumor necrosis factor receptor (TNFR) family signal largely through
      interactions with death domain proteins and TRAF proteins. Here we report the
      identification of a novel TNFR family member ATAR. Human and mouse ATAR contain
      283 and 276 amino acids, respectively, making them the shortest known members of
      the TNFR superfamily. The receptor is expressed mainly in spleen, thymus, bone
      marrow, lung, and small intestine. The intracellular domains of human and mouse
      ATAR share only 25% identity, yet both interact with TRAF5 and TRAF2. This TRAF
      interaction domain resides at the C-terminal 20 amino acids. Like most other TRAF
      interacting receptors, overexpression of ATAR activates the transcription factor
      NF-kappaB. Co-expression of ATAR with TRAF5, but not TRAF2, results in
      synergistic activation of NF-kappaB, suggesting potentially different roles for
      TRAF2 and TRAF5 in post-receptor signaling.

PMID- 9153190
TI  - The second extracellular loop of the prostaglandin EP3 receptor is an essential
      determinant of ligand selectivity.
AB  - The prostaglandin EP3 receptor binds Prostaglandin E2 in a ligand binding pocket
      formed in part by seven transmembrane alpha-helices. The present studies
      demonstrate that the second extracellular loop of the receptor is involved in
      prostanoid ligand recognition as well. Site-directed mutagenesis of seven
      conserved residues clustered in the amino portion of the second extracellular
      loop was performed. Receptors with single amino acid substitutions at each of
      these positions were transiently transfected into HEK293tsA201 cells, their
      ligand binding profiles assessed, and each receptor was tested for its ability to
      decrease intracellular cAMP levels. Substitution of Trp199 or Thr202 with alanine
      resulted in receptors with increases in affinity up to 128-fold for prostanoid
      compounds with a C1 methyl ester but wild type affinities for natural prostanoid
      ligands that have a carboxylate moiety at the C1 position. In contrast,
      substitution of Pro200 with serine caused a loss of selectivity up to 20-fold for
      naturally occurring prostanoid agonists as compared with the wild type EP3
      receptor: the PS200 receptor displayed a decrease in affinity for E-ring
      compounds and an increase in affinity for F- and D-ring compounds. The EC50 for
      inhibition of cAMP remained unchanged for each receptor tested.

PMID- 9153191
TI  - A Rab GTPase is required for homotypic assembly of the endoplasmic reticulum.
AB  - To define the requirements for the homotypic fusion of mammalian endoplasmic
      reticulum (ER) membranes, we have developed a quantitative in vitro enzyme-linked
      immunosorbent assay. This assay measures the formation of IgG (H2L2) following
      the fusion of ER microsomes containing either the heavy or light chain subunits.
      Guanine nucleotide dissociation inhibitor (GDI), a protein that extracts Rab
      GTPases in the GDP-bound form from membranes, potently inhibits fusion.
      Inhibition was not observed using GDI mutants defective in Rab binding. Kinetic
      analysis of the inhibitory effects of GDI revealed that Rab activation is
      required immediately preceding or coincident with fusion and that this step is
      preceded by a priming event requiring a member of the AAA ATPase family. Our
      results suggest that homotypic fusion of ER membranes requires Rab and that Rab
      activation is a transient event necessary for the formation of a fusion pore
      leading to the mixing of luminal contents of ER microsomes.

PMID- 9153192
TI  - Inhibition of protein geranylgeranylation causes a superinduction of nitric-oxide
      synthase-2 by interleukin-1beta in vascular smooth muscle cells.
AB  - Recently, we have designed farnesyltransferase and geranylgeranyltransferase I
      inhibitors (FTI-277 and GGTI-298) that selectively block protein farnesylation
      and geranylgeranylation, respectively. In this study, we describe the opposing
      effects of these inhibitors on interleukin-1beta (IL-1beta)-stimulated induction
      of nitric-oxide synthase-2 (NOS-2) in rat pulmonary artery smooth muscle cells
      (RPASMC) and rat hepatocytes. Pretreatment of cells with GGTI-298 caused a
      superinduction of NOS-2 by IL-1beta. RPASMC treated with GGTI-298 (10 microM)
      prior to IL-1beta (10 ng/ml) expressed levels of NOS-2 protein five times higher
      than those exposed to IL-1beta alone. This superinduction of NOS-2 protein by
      pretreatment with GGTI-298 resulted in nitrite concentrations in the medium that
      were 5-fold higher at 10 ng/ml IL-1beta and 10-fold higher at 1 ng/ml IL-1beta.
      Furthermore, NOS-2 mRNA levels in RPASMC were also increased 6- and 14-fold (at
      10 and 1 ng/ml IL-1beta, respectively) when the cells were pretreated with GGTI
      298. In contrast, treatment of cells with the inhibitor of protein farnesylation,
      FTI-277 (10 microM), blocked IL-1beta-induced NOS-2 expression at mRNA and
      protein levels. Pretreatment with lovastatin, an inhibitor of protein
      prenylation, resulted in superinduction of NOS-2. This superinduction was
      reversed by geranylgeraniol, but not by farnesol, further confirming that
      inhibition of geranylgeranylation, not farnesylation, is responsible for enhanced
      NOS-2 expression. The results demonstrate that a farnesylated protein(s) mediates
      IL-1beta induction of NOS-2, whereas a geranylgeranylated protein(s) represses
      this induction.

PMID- 9153193
TI  - Casein kinase II-mediated phosphorylation of the C terminus of Sp1 decreases its
      DNA binding activity.
AB  - We have previously observed that Sp1, a ubiquitous zinc finger transcription
      factor, is phosphorylated during terminal differentiation in the whole animal,
      and this results in decreased DNA binding activity (Leggett, R. W., Armstrong, S.
      A., Barry, D., and Mueller, C. R. (1995) J. Biol. Chem. 270, 25879-25884). In
      this study, we demonstrate that casein kinase II (CKII) is able to phosphorylate
      the C terminus of Sp1 and results in a decrease in DNA binding activity. This
      suggests that CKII may be responsible for the observed regulation of Sp1.
      Mutation of a consensus CKII site at amino acid 579, within the second zinc
      finger, eliminates phosphorylation of this site and the CKII-mediated inhibition
      of Sp1 binding. Phosphopeptide analysis confirms the presence of a CKII site at
      Thr-579 as well as additional sites within the C terminus. No gross changes in
      CKII subunit levels were seen during de-differentiation associated with liver
      regeneration. The serine/threonine phosphatase PP1 was identified as the
      endogenous liver nuclear protein able to dephosphorylate Sp1 but again no gross
      changes in activity were observed in the regenerating liver. Okadaic acid
      treatment of K562 cells increases Sp1 phosphorylation and inhibits its DNA
      binding activity suggesting that steady state levels of Sp1 phosphorylation are
      established by a balance between kinase and phosphatase activities.

PMID- 9153194
TI  - Fusion peptides derived from the HIV type 1 glycoprotein 41 associate within
      phospholipid membranes and inhibit cell-cell Fusion. Structure-function study.
AB  - The fusion domain of human immunodeficiency virus (HIV-1) envelope glycoprotein
      (gp120-gp41) is a conserved hydrophobic region located at the N terminus of the
      transmembrane glycoprotein (gp41). A V2E mutant has been shown to dominantly
      interfere with wild-type envelope-mediated syncytium formation and virus
      infectivity. To understand this phenomenon, a 33-residue peptide (wild type, WT)
      identical to the N-terminal segment of gp41 and its V2E mutant were synthesized,
      fluorescently labeled, and characterized. Both peptides inhibited HIV-1 envelope
      mediated cell-cell fusion and had similar alpha-helical content in membrane
      mimetic environments. Studies with fluorescently labeled peptide analogues
      revealed that both peptides have high affinity for phospholipid membranes, are
      susceptible to digestion by proteinase-K in their membrane-bound state, and tend
      to self- and coassemble in the membranes. In SDS-polyacrylamide gel
      electrophoresis the WT peptide formed dimers as well as higher order oligomers,
      whereas the V2E mutant only formed dimers. The WT, but not the V2E mutant,
      induced liposome aggregation, destabilization, and fusion. Moreover, the V2E
      mutant inhibited vesicle fusion induced by the WT peptide, probably by forming
      inactive heteroaggregates. These data form the basis for an explanation of the
      mechanism by which the gp41 V2E mutant inhibits HIV-1 infectivity in cells when
      co-expressed with WT gp41.

PMID- 9153195
TI  - Characterization of simian malarial parasite (Plasmodium knowlesi)-induced
      putrescine transport in rhesus monkey erythrocytes. A novel putrescine conjugate
      arrests in vitro growth of simian malarial parasite (Plasmodium knowlesi) and
      cures multidrug resistant murine malaria (Plasmodium yoelii) infection in vivo.
AB  - A stage-dependent increase in the level of putrescine, spermidine, and spermine
      during intraerythrocytic growth of Plasmodium knowlesi in rhesus monkey
      erythrocytes was observed. Further, intraerythrocytic P. knowlesi-induced
      putrescine influx was found in trophozoite stage-infected erythrocytes and
      process was time- and temperature-dependent and showed saturable kinetics.
      Characteristics of induced putrescine influx appears in infected erythrocytes to
      be close to the normal erythrocytes in terms of affinity of putrescine to the
      putrescine transporter (Km 34.6 +/- 3.8 microM as normal erythrocytes and Km 37.2
      +/- 5.2 microM in infected erythrocytes). However, the difference involves the
      significant increase in the putrescine influx rate after infection (Vmax = 4.21
      nmol/min/10(10) normal erythrocytes, compared with 11.6 nmol/min/10(10) infected
      erythrocytes). Energy dependence, involvement of -SH group, and noninterference
      by amino acid, spermidine, and spermine in the putrescine influx process clearly
      demonstrate the presence of a distinct transporter for putrescine in infected
      erythrocytes. A putrescine conjugate N1,N4-bis(7-chloroquinoline-4-yl)butane-1, 4
      diamine (BCBD) was synthesized, which inhibits the putrescine influx in the P.
      knowlesi infected erythrocytes (Ki of 43.2 microM) as well as in vitro growth of
      P. knowlesi (IC50 value, 7.64 +/- 0.97 ng/ml BCBD, 10.8 +/- 0.45 ng/ml
      chloroquine). Addition of exogenous polyamines failed to reverse the inhibitory
      effect of BCBD in vitro. Administration of BCBD (24 mg/kg body weight,
      intraperitoneal, twice a day for 4 days) cured the Swiss mice infected with
      multidrug-resistant infection of Plasmodium yoelii. Therefore, inhibition of
      putrescine transport in malaria-infected erythrocytes offers a lead in the search
      of a new class of chemotherapeutic molecules against malaria.

PMID- 9153196
TI  - Catalytic properties of murine carbonic anhydrase IV.
AB  - A cDNA encoding the murine carbonic anhydrase IV (mCA IV) gene, modified to
      resemble a form of mature human carbonic anhydrase IV (Okuyama, T., Waheed, A.,
      Kusumoto, W., Zhu, X. L., and Sly, W. S. (1995) Arch. Biochem. Biophys. 320, 315
      322), was expressed in Escherichia coli. Inactive inclusion bodies were collected
      and refolded, and active enzyme was purified; the resulting mCA IV was used to
      characterize the catalysis of CO2 hydration using stopped flow spectrophotometry
      and 18O exchange between CO2 and water. Unlike previously studied isozymes in
      this class of carbonic anhydrase, the pH profile for kcat for hydration of CO2
      catalyzed by mCA IV could not be described by a single ionization, suggesting
      multiple proton transfer pathways between the zinc-bound water molecule and
      solution. A role for His64 in transferring protons between the zinc-bound water
      and solution was confirmed by the 100-fold lower activity of the mutant of mCA IV
      containing the replacement His64 --> Ala. The remaining activity in this mutant
      at pH levels near 9 suggested a second proton shuttle mechanism. The maximal
      turnover number kcat for hydration of CO2 catalyzed by mCA IV was 1.1 x 10(6) s-1
      at pH > 9. A pKa of 6.6 was estimated for the zinc-bound water molecule in mCA
      IV.

PMID- 9153197
TI  - p260/270 expressed in embryonic abdominal leg cells of Bombyx mori can transfer
      palmitate to peptides.
AB  - During the study on the mechanisms of abdominal leg development in the silkworm
      Bombyx mori, we found that a high molecular mass protein (p260/270) was expressed
      specifically in abdominal leg cells during early embryonic stages and disappeared
      by a late embryonic stage. p260/270 consists of two polypeptides with molecular
      masses of 260 and 270 kDa. We have established a purification procedure for
      p260/270 and have raised an antibody against p260/270. Immunoblot analysis of the
      ECa/ECa (additional crescent) and EN/EN (new additional crescent) mutants, which
      lack the Bombyx abdominal-A gene and therefore do not express abdominal legs,
      demonstrated that the two mutants lacked p260/270. Therefore, we speculate that
      the expression of p260/270 may be regulated by the Bombyx abdominal-A gene. cDNA
      cloning and sequencing demonstrated that p260 and p270 have structures similar to
      that of rat fatty-acid synthase, which synthesizes palmitate. Most of the
      enzymatic domains for palmitate synthesis were well conserved in the amino acid
      sequences of p260 and p270, while the thioesterase domains of p260 and p270 were
      less homologous to that of rat fatty-acid synthase. Purified p260/270 can
      transfer palmitate to cysteine residues of synthetic peptides in vitro. We
      propose that p260/270 may be involved in protein palmitoylation and may function
      in abdominal leg development.

PMID- 9153198
TI  - A novel matrix metalloproteinase gene (XMMP) encoding vitronectin-like motifs is
      transiently expressed in Xenopus laevis early embryo development.
AB  - To study the role of matrix metalloproteinases (MMPs) in early vertebrate
      development, we cloned cDNAs for six different MMPs from the frog Xenopus laevis
      embryos at different stages of development and describe here a novel MMP called
      XMMP. Xenopus XMMP has 604 amino acids including a putative signal peptide of 22
      residues. At the carboxyl-terminal end of the propeptide, XMMP has a 37-amino
      acid-long insertion domain containing a segment that is 38% identical with a rat
      vitronectin sequence between residues 108-135. Following this domain is an RRKR
      motif, a putative cleavage site for intracellular activation by furin
      proteinases. XMMP lacks a proline-rich linker peptide, or hinge region, typically
      found in other MMPs between the catalytic domain and carboxyl-terminal
      "hemopexin/vitronectin-like" domain. In XMMP, the carboxyl-terminal domain is
      composed of four tandem repeats that are 21-33% identical to a sequence (residues
      213-264) encoded by vitronectin exon-5. Interestingly, XMMP gene is transiently
      expressed during Xenopus embryo development. XMMP mRNA of 3.0 kilobase pairs was
      undetected in the blastula stage embryo, induced in gastrula embryo, expressed in
      neurula embryo, and then down-regulated in pretailbud embryo. In comparison,
      other Xenopus MMP genes that we have cloned show a different developmental
      regulation. In blastula embryo, the only MMP gene expressed was found to be 92
      kDa type IV collagenase, which was also expressed in the gastrula, neurula, and
      pretailbud embryos. Expression of stromelysin-1, stromelysin-3, and two different
      membrane type-MMPs was first detected in the neurula and pretailbud embryos.
      These results suggest that MMPs and the novel XMMP reported here play a role in
      Xenopus early development.

PMID- 9153199
TI  - Differential activation of protein kinase C delta and epsilon gene expression by
      gonadotropin-releasing hormone in alphaT3-1 cells. Autoregulation by protein
      kinase C.
AB  - The effect of gonadotropin-releasing hormone (GnRH) upon protein kinase C (PKC)
      delta and PKCepsilon gene expression was investigated in the gonadotroph-derived
      alphaT3-1 cell line. Stimulation of the cells with a stable analog [D-Trp6]GnRH
      (GnRH-A) resulted in a rapid elevation of PKCepsilon mRNA levels (1 h), while
      PKCdelta mRNA levels were elevated only after 24 h of incubation. The rapid
      elevation of PKCepsilon mRNA by GnRH-A was blocked by pretreatment with a GnRH
      antagonist or actinomycin D. The PKC activator 12-O-tetradecanoylphorbol-13
      acetate (TPA), but not the Ca2+ ionophore ionomycin, mimicked the rapid effect of
      GnRH-A upon PKCepsilon mRNA elevation. Additionally, the rapid stimulatory effect
      of GnRH-A was blocked by the selective PKC inhibitor GF109203X, by TPA-mediated
      down-regulation of endogenous PKC, or by Ca2+ removal. Interestingly, serum
      starvation (24 h) advanced the stimulation of PKCdelta mRNA levels by GnRH-A and
      the effect could be detected at 1 h of incubation. The rapid effect of GnRH-A
      upon PKCdelta mRNA levels in serum-starved cells was mimicked by TPA, but not by
      ionomycin, and was abolished by down-regulation of PKC or by Ca2+ removal.
      Preactivation of alphaT3-1 cells with GnRH-A for 1 h followed by removal of
      ligand and serum resulted in elevation of PKCdelta mRNA levels after 24 h of
      incubation. Western blot analysis revealed that GnRH-A and TPA stimulated (within
      5 min) the activation and some degradation of PKCdelta and PKCepsilon. We
      conclude that Ca2+ and PKC are involved in GnRH-A elevation of PKCdelta and
      PKCepsilon mRNA levels, with Ca2+ being necessary but not sufficient, while PKC
      is both necessary and sufficient to mediate the GnRH-A response. A serum factor
      masks PKCdelta but not PKCepsilon mRNA elevation by GnRH-A, and its removal
      exposes preactivation of PKCdelta mRNA by GnRH-A which can be memorized for 24 h.
      PKCdelta and PKCepsilon gene expression evoked by GnRH-A is autoregulated by PKC,
      and both isotypes might participate in the neurohormone action.

PMID- 9153200
TI  - Zinc as a cofactor for heparin neutralization by histidine-rich glycoprotein.
AB  - We have studied the ability of histidine-rich glycoprotein (HRG) to neutralize
      the anticoagulant activity of heparin in plasma and in a purified component
      clotting assay. Addition of HRG to plasma or to the purified component assay did
      not neutralize the anticoagulant activity of heparin unless micromolar
      concentrations of zinc were present. Higher zinc concentrations were required for
      citrated than for heparinized plasmas due to competition of citrate with HRG for
      zinc binding. Zinc concentrations as low as 1.25 microM revealed HRG to be a
      powerful competitor of antithrombin for heparin in the purified component assays.
      HRG binding of heparin also was shown by affinity chromatography of HRG from
      immobilized heparin in the presence and absence of zinc. In the absence of zinc,
      HRG was eluted by 0.1 M NaCl, but, in the presence of zinc, elution of HRG
      required 1.0 M NaCl. Investigation of other divalent cations (copper and
      magnesium) indicated that augmentation of heparin binding by HRG in the presence
      of antithrombin was restricted to zinc. The HRG.Zn complex effectively competes
      with antithrombin for heparin, which restricts the availability of heparin to
      bind antithrombin and allows thrombin-mediated fibrinogenesis to proceed
      unimpeded. This could be initiated by zinc released from activated platelets.

PMID- 9153201
TI  - Physical interaction between specific E2 and Hect E3 enzymes determines
      functional cooperativity.
AB  - The cellular protein E6AP functions as an E3 ubiquitin protein ligase in the E6
      dependent ubiquitination of p53. E6AP is a member of a family of functionally
      related E3 proteins that share a conserved carboxyl-terminal region called the
      Hect domain. Although several different E2 ubiquitin-conjugating enzymes have
      been shown to function with E6AP in the E6-dependent ubiquitination of p53 in
      vitro, the E2s that cooperate with E6AP in the ubiquitination of its normal
      substrates are presently unknown. Moreover, the basis of functional cooperativity
      between specific E2 and Hect E3 proteins has not yet been determined. Here we
      report the cloning of a new human E2, designated UbcH8, that was identified in a
      two-hybrid screen through specific interaction with E6AP. We demonstrate that
      UbcH7, an E2 closely related to UbcH8, can also bind to E6AP. The region of E6AP
      involved in complex formation with UbcH8 and UbcH7 was mapped to its Hect domain.
      Furthermore, we show that UbcH5 and UbcH6, two highly homologous E2s that were
      deficient for interaction with E6AP, could associate efficiently with another
      Hect-E3 protein, RSP5. Finally, only the E6AP-interacting E2s could function in
      conjunction with E6AP in the ubiquitination of an E6 independent substrate of
      E6AP, whereas the noninteracting E2s could not. Taken together, these studies
      demonstrate for the first time complex formation between specific human E2s and
      the Hect domain family of E3 proteins and suggest that selective physical
      interaction between E2 and E3 enzymes forms the basis of specificity for
      functionally distinct E2:E3 combinations.

PMID- 9153202
TI  - Effect of leader peptides on the permeability of mitochondria.
AB  - Peptides with sequences based on the leader sequence of yeast cytochrome c
      oxidase subunit IV (pCOX IV-(1-25)) activate the electrophoretic uptake of K+ and
      other cations such as tetraethylammonium and lysine by rat liver mitochondria
      with EC50 = 11-15 microM. Uptake of these cations is dependent on respiration and
      is prevented by uncoupling agents, and the Vmax for K+ is 1.2-1.5
      micromol/min/mg. Albeit more slowly, the non-electrolytes mannitol and sucrose
      are also transported by this pathway. Treatment of the peptides with proteinase K
      eliminates the stimulatory effect. Since the stimulated rate is not inhibited by
      ATP or by cyclosporin, we conclude that this pathway is not related to the
      mitochondrial KATP channel or the Ca2+-dependent permeability transition pore.
      Transport is stimulated by pCOX IV-(1-23), pCOX IV-(1-22), and pCOX IV-(1-12)Y,
      but not by a 13-amino acid peptide representing the nuclear location sequence of
      the SV40 large T antigen, which is responsible for directing that protein to the
      nucleus. Spermine, which has four positive charges, also has no stimulatory
      effect, and an amphiphilic 22-residue peptide derived from antithrombin III with
      seven net charges is only one-twentieth as effective as pCOX IV-(1-22). Thus,
      these data indicate that the sequence/structure is important for activation of
      transport. We also demonstrate that mitochondrial uncoupling, previously reported
      to be induced by these peptides, actually reflects coupled accumulation of salt.
      In view of our findings, it is also likely that the lytic effects attributed to
      these peptides are secondary to swelling and are not due to membrane damage per
      se. Finally, we show that, in non-ionic media, the peptide is an inhibitor of
      cytochrome c oxidase.

PMID- 9153203
TI  - Characterization of cyanobacterial biliverdin reductase. Conversion of biliverdin
      to bilirubin is important for normal phycobiliprotein biosynthesis.
AB  - The Synechocystis sp. PCC 6803 gene (bvdR) encoding biliverdin reductase was
      amplified by the polymerase chain reaction, cloned, and overexpressed in
      Escherichia coli as the native form and as a 6-histidine-tagged amino-terminal
      fusion. The latter form of the enzyme was purified by affinity chromatography and
      shown to have the appropriate molecular weight by electrospray mass spectrometry.
      Both forms of the enzyme reduced biliverdin IXalpha using NADPH or NADH, with
      NADPH as the preferred reductant. The His-tagged enzyme has a Km for biliverdin
      of 1.3 microM. The pH optimum for the NADPH-dependent activity is 5.8, whereas
      that for rat biliverdin reductase is at pH 8.7. Absorbance spectra and high
      performance liquid chromatography retention times of the reaction product
      reaction match those of authentic bilirubin, the product of the reduction of
      biliverdin by the mammalian enzymes. These results provide the first evidence for
      the formation of bilirubin in bacteria. Fully segregated Synechocystis sp. PCC
      6803 bvdR interposon mutants produce approximately 85% of the normal amount of
      phycobilisome cores containing allophycocyanin and other phycocyanobilin-bearing
      core polypeptides, but no detectable phycocyanin. Thus, surprisingly, the
      blockage of the conversion of biliverdin to bilirubin interferes with normal
      phycobiliprotein biosynthesis in cyanobacteria. Possible interpretations of this
      finding are presented.

PMID- 9153204
TI  - Hepatic lipase deficiency increases plasma cholesterol but reduces susceptibility
      to atherosclerosis in apolipoprotein E-deficient mice.
AB  - The effect of hepatic lipase (HL) deficiency on the susceptibility to
      atherosclerosis was tested using mice with combined deficiencies in HL and apoE.
      Mice lacking both HL and apoE (hhee) have a plasma total cholesterol of 917 +/-
      252 mg/dl (n = 24), which is 184% that of mice lacking only apoE (HHee; 497 +/-
      161 mg/dl, n = 20, p < 0. 001). The increase in cholesterol was mainly in beta
      migrating very low density lipoproteins, although high density lipoprotein
      cholesterol (HDLc) was also increased (53 +/- 37 versus 20 +/- 13 mg/dl, p <
      0.01). Despite the increase in plasma cholesterol, we found that HL deficiency
      significantly decreased aortic plaque sizes in female mice fed normal chow (31 x
      10(3) +/- 22 x 10(3) microm2 in hhee versus 115 x 10(3) +/- 69 x 10(3) microm2 in
      HHee, p < 0.001). Reduction of plaque sizes was also observed in female
      heterozygous apoE-deficient mice fed an atherogenic diet (2 x 10(3) +/- 2.5 x
      10(3) microm2 in hhEe versus 56 x 10(3) +/- 49 x 10(3) microm2 in HHEe, p <
      0.01). Changes in aortic lesion size were not apparent in the small number of
      male mice studied. In HHee females, both HDLc and the capacity of high density
      lipoprotein (HDL) particles to promote cholesterol efflux from cultured cells
      were 26% of the wild type. The absence of HL in hhee females partially restored
      HDLc levels to 57% and cholesterol efflux to 55% of the wild type. Circulating
      pre-beta1-migrating HDL were present in all mutants, suggesting that there are
      alternative pathways in the formation of these pre-beta-HDL not involving apoE,
      HL, or cholesteryl ester transfer protein. The improved capacity to promote
      cholesterol efflux, together with increased HDL, may explain why these animals
      can overcome the increase in atherogenic lipoproteins.

PMID- 9153205
TI  - Platelet activation and signal transduction by convulxin, a C-type lectin from
      Crotalus durissus terrificus (tropical rattlesnake) venom via the p62/GPVI
      collagen receptor.
AB  - Convulxin, a powerful platelet activator, was isolated from Crotalus durissus
      terrificus venom, and 20 amino acid N-terminal sequences of both subunits were
      determined. These indicated that convulxin belongs to the heterodimeric C-type
      lectin family. Neither antibodies against GPIb nor echicetin had any effect on
      convulxin-induced platelet aggregation showing that, in contrast to other venom C
      type lectins acting on platelets, GPIb is not involved in convulxin-induced
      platelet activation. In addition, partially reduced/denatured convulxin only
      affects collagen-induced platelet aggregation. The mechanism of convulxin-induced
      platelet activation was examined by platelet aggregation, detection of time
      dependent tyrosine phosphorylation of platelet proteins, and binding studies with
      125I-convulxin. Convulxin induces signal transduction in part like collagen,
      involving the time-dependent tyrosine phosphorylation of Fc receptor gamma chain,
      phospholipase Cgamma2, p72(SYK), c-Cbl, and p36-38. However, unlike collagen,
      pp125(FAK) and some other bands are not tyrosine-phosphorylated. Convulxin binds
      to a glycosylated 62-kDa membrane component in platelet lysate and to p62/GPVI
      immunoprecipitated by human anti-p62/GPVI antibodies. Convulxin subunits inhibit
      both aggregation and tyrosine phosphorylation in response to collagen.
      Piceatannol, a tyrosine kinase inhibitor with some specificity for p72(SYK),
      showed differential effects on collagen and convulxin-stimulated signaling. These
      results suggest that convulxin uses the p62/GPVI but not the alpha2beta1 part of
      the collagen signaling pathways to activate platelets. Occupation and clustering
      of p62/GPVI may activate Src family kinases phosphorylating Fc receptor gamma
      chain and, by a mechanism previously described in T- and B-cells, activate
      p72(SYK) that is critical for downstream activation of platelets.

PMID- 9153206
TI  - Demonstration of a metabolically active glucose-6-phosphate pool in the lumen of
      liver microsomal vesicles.
AB  - Glucose-6-phosphate transport was investigated in rat or human liver microsomal
      vesicles using rapid filtration and light-scattering methods. Upon addition of
      glucose-6-phosphate, rat liver microsomes accumulated the radioactive tracer,
      reaching a steady-state level of uptake. In this phase, the majority of the
      accumulated tracer was glucose, but a significant intraluminal glucose-6
      phosphate pool could also be observed. The extent of the intravesicular glucose
      pool was proportional with glucose-6-phosphatase activity. The relative size of
      the intravesicular glucose-6-phosphate pool (irrespective of the concentration of
      the extravesicular concentration of added glucose-6-phosphate) expressed as the
      apparent intravesicular space of the hexose phosphate was inversely dependent on
      glucose-6-phosphatase activity. The increase of hydrolysis by elevating the
      extravesicular glucose-6-phosphate concentration or temperature resulted in lower
      apparent intravesicular glucose-6-phosphate spaces and, thus, in a higher
      transmembrane gradient of glucose-6-phosphate concentrations. In contrast,
      inhibition of glucose-6-phosphate hydrolysis by vanadate, inactivation of glucose
      6-phosphatase by acidic pH, or genetically determined low or absent glucose-6
      phosphatase activity in human hepatic microsomes of patients suffering from
      glycogen storage disease type 1a led to relatively high intravesicular glucose-6
      phosphate levels. Glucose-6-phosphate transport investigated by light-scattering
      technique resulted in similar traces in control and vanadate-treated rat
      microsomes as well as in microsomes from human patients with glycogen storage
      disease type 1a. It is concluded that liver microsomes take up glucose-6
      phosphate, constituting a pool directly accessible to intraluminal glucose-6
      phosphatase activity. In addition, normal glucose-6-phosphate uptake can take
      place in the absence of the glucose-6-phosphatase enzyme protein, confirming the
      existence of separate transport proteins.

PMID- 9153207
TI  - Analysis of the secretory phospholipase A2 that mediates prostaglandin production
      in mast cells.
AB  - Prostaglandin D2 (PGD2) synthesis in activated mast cells occurs in two phases,
      an early phase that is dependent on prostaglandin synthase 1 and a delayed phase
      that is dependent on activation-induced prostaglandin synthase 2 gene expression.
      Early phase PGD2 synthesis in activated mast cells also requires the activity of
      a secretory phospholipase A2 (PLA2). It has been thought that the secretory PLA2
      expressed in mast cells is group IIa PLA2, encoded by the Pla2 g2a gene. However,
      activated bone marrow-derived mast cells prepared from Pla2 g2a+/+ mice and mast
      cells prepared from mice with a mutation in the Pla2 g2a gene both demonstrate
      early phase PGD2 synthesis. Moreover, mast cells from both murine strains secrete
      PLA2 activity following activation. Northern and reverse transcriptase/polymerase
      chain reaction analyses demonstrate that mast cells from Pla2 g2a+/+ and Pla2 g2a
      /- mice do not express group IIa PLA2 message. Instead, Northern and reverse
      transcriptase/polymerase chain reaction analyses demonstrate that both Pla2
      g2a+/+ and Pla2 g2a-/- mast cells express mRNA for group V PLA2, encoded by the
      Pla2gV gene. An antisense oligonucleotide directed against group V PLA2 is also
      able to inhibit both the early phase of PGD2 production and the secretion of PLA2
      activity by activated mast cells. Our data suggest that (i) group IIa PLA2 does
      not play a significant role in murine mast cell prostaglandin synthesis, (ii)
      group V PLA2 mediates early mast cell PGD2 production and transcellular PGE2
      production in murine mast cells, and (iii) much of the data, based on studies
      with chemical inhibitors and antibodies, suggesting that group IIa PLA2 is
      responsible for arachidonic acid mobilization needs to be reevaluated.

PMID- 9153208
TI  - Structural identification by mass spectrometry of oxidized phospholipids in
      minimally oxidized low density lipoprotein that induce monocyte/endothelial
      interactions and evidence for their presence in vivo.
AB  - Entry of monocytes into the vessel wall is an important event in atherogenesis.
      Previous studies from our laboratory suggest that oxidized arachidonic acid
      containing phospholipids present in mildly oxidized low density lipoproteins (MM
      LDL) can activate endothelial cells to bind monocytes. In this study,
      biologically active oxidized arachidonic acid-containing phospholipids were
      produced by autoxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3
      phosphocholine (Ox-PAPC) and analyzed by liquid chromatography and electrospray
      ionization mass spectrometry in conjuction with biochemical derivatization
      techniques. We have now determined the molecular structure of two of three
      molecules present in MM-LDL and Ox-PAPC that induce monocyte-endothelial
      interactions. These lipids were identified as 1-palmitoyl-2-(5-oxovaleryl)-sn
      glycero-3-phosphocholine (m/z 594.3) and 1-palmitoyl-2-glutaryl-sn-glycero-3
      phosphocholine (m/z 610.2). These two molecules were produced by unambiguous
      total synthesis and found to be identical by analytical techniques and
      bioactivity assays to those present in MM-LDL and Ox-PAPC. Evidence for the
      importance of all three oxidized phospholipids in vivo was suggested by their
      presence in fatty streak lesions from cholesterol-fed rabbits and by their
      immunoreactivity with natural antibodies present in ApoE null mice. Overall,
      these studies suggest that specific oxidized derivatives of arachidonic acid
      containing phospholipids may be important initiators of atherogenesis.

PMID- 9153210
TI  - Porins of Haemophilus influenzae type b mutated in loop 3 and in loop 4.
AB  - Porin (341 amino acids; mass of 37,782 Da) in the outer membrane of Haemophilus
      influenzae type b (Hib) permits diffusion into the periplasm of small solutes up
      to a molecular mass of 1400 Da. Molecular modeling of Hib porin identified its
      structural similarities to OmpF of Escherichia coli and disclosed for Hib porin a
      shorter length of loop 3 and a longer length of loop 4. By site-directed
      mutagenesis of the porin gene ompP2, mutant porins were constructed to contain 6
      or 12 amino acid deletions either in loop 3 or in surface-exposed loop 4. Wild
      type Hib porin and mutant porins were expressed in a nontypeable H. influenzae
      strain deleted for the ompP2 gene. The mutant porins were purified and
      reconstituted into planar bilayers, tested for channel formation and compared
      with wild type Hib porin. Mutant Haemophilus porin possessing a 6-amino acid
      deletion in loop 3 displayed a broad distribution of single channel conductance
      values, while deletion of 12 amino acids from the same loop destabilized the
      porin channel. By comparison, deletion of 6 or of 12 amino acids from loop 4 of
      Hib porin resulted in an increased single channel conductance (1.15 and 1.05
      nanosiemens, respectively) compared with wild type Hib porin (0. 85 nanosiemens).
      The C3 epitope of the poliovirus VP1 capsid protein was inserted either into loop
      3 or into loop 4 of Hib porin. By flow cytometry, the C3 epitope was detected as
      surface-exposed in strains expressing C3 insertion in loop 4; in strains
      expressing C3 insertion in loop 3, the epitope was inaccessible. We propose that
      loop 4 of Hib porin, although surface-accessible, is oriented toward the central
      axis of the pore and that deletions in this loop increase the single channel
      conductance by widening the pore entrance.

PMID- 9153209
TI  - Molecular analysis of ligand binding to the second cluster of complement-type
      repeats of the low density lipoprotein receptor-related protein. Evidence for an
      allosteric component in receptor-associated protein-mediated inhibition of ligand
      binding.
AB  - The low density lipoprotein receptor-related protein (LRP), a member of the low
      density lipoprotein receptor gene family, mediates the cellular uptake of a
      diversity of ligands. A folding chaperone, the 39-kDa receptor-associated protein
      (RAP) that resides in the early compartments of the secretory pathway inhibits
      the binding of all ligands to the receptor and may serve to prevent premature
      binding of ligands to the receptor during the trafficking to the cell surface. To
      elucidate the molecular interactions that underlie the interplay between the
      receptor, RAP, and the ligands, we have analyzed and delineated the binding sites
      of plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator
      (t-PA).PAI-1 complexes, RAP, and the anti-LRP Fab fragment Fab A8. To that end,
      we have generated a series of soluble recombinant fragments spanning the second
      cluster of complement-type repeats (C3-C10) and the amino-terminal flanking
      epidermal growth factor repeat (E4) of LRP (E4-C10; amino acids 787-1165). All
      fragments were expressed by stably transfected baby hamster kidney cells and
      purified by affinity chromatography. A detailed study of ligand binding to the
      fragments using surface plasmon resonance revealed the presence of three
      distinct, Ca2+-dependent ligand binding sites in the cluster II domain (Cl-II) of
      LRP. t-PA.PAI-1 complexes as well as PAI-1 bind to a domain located in the amino
      terminal portion of Cl-II, spanning repeats E4-C3-C7. Adjacent to this site and
      partially overlapping is a high affinity RAP-binding site located on repeats C5
      C7. Fab A8, a pseudo-ligand of the receptor, binds to a third Ca2+-dependent
      binding site on repeats C8-C10 at the carboxyl-terminal end of Cl-II. Next, we
      studied the RAP-mediated inhibition of ligand binding to LRP and to Cl-II. As
      expected, we observed a strong inhibition of t-PA.PAI-1 complex and Fab A8
      binding to LRP by RAP (IC50 congruent with 0.3 nM), whereas in the reverse
      experiment, competition of t-PA. PAI-1 complexes and Fab A8 for RAP binding to
      LRP could only be shown at high concentrations of competitors (>/=1 microM).
      Interestingly, even though the equilibrium dissociation constants for the binding
      of RAP to LRP and to Cl-II are similar, the binding of the ligands to Cl-II is
      only prevented by RAP at concentrations that are at least 2 orders of magnitude
      higher than those required for inhibition of ligand binding to LRP. Our results
      favor models that propose RAP-induced allosteric inhibition of ligand binding to
      LRP that may require LRP moieties that are located outside Cl-II of the receptor.

PMID- 9153211
TI  - A soluble form of alpha1,3-galactosyltransferase functions within cells to
      galactosylate glycoproteins.
AB  - It has been assumed that membrane-bound glycosyltransferases function within the
      Golgi apparatus to glycosylate glycoproteins. We now report, however, that a
      truncated, soluble recombinant form of the murine alpha1,3-galactosyltransferase
      expressed in human 293 cells is highly efficient and comparable to the full
      length enzyme in alpha-galactosylating both newly synthesized membrane-associated
      and secreted glycoproteins. Although the soluble enzyme was secreted by cells as
      expected, we also found that the full-length, membrane-associated form was
      secreted. Unexpectedly, both secreted forms are cleaved identically at two
      primary sites within the stem region by endogenous protease(s) at the indicated
      positions in the sequence 73KDWW (downward arrow) FPS (downward arrow) WFKNG.
      These results demonstrate that the soluble alpha1,3-galactosyltransferase is
      functional within the cell and that specific proteolysis occurs in the stem
      region. The widespread occurrence of different soluble glycosyltransferases
      secreted by cells suggests that normal glycoconjugate biosynthesis may involve
      cooperation between membrane-bound and soluble enzymes.

PMID- 9153212
TI  - Kinetic mechanism of the hairpin ribozyme. Identification and characterization of
      two nonexchangeable conformations.
AB  - To investigate the relationship between RNA folding and ribozyme catalysis, we
      have carried out a detailed kinetic analysis of four structural derivatives of
      the hairpin ribozyme. Optimal and suboptimal (wild-type) substrate sequences were
      studied in conjunction with stabilization of helix 4, which supports formation of
      the catalytic core. Pre-steady-state and steady-state kinetic studies strongly
      support a model in which each of the ribozyme variants partitions between two
      major conformations leading to active and inactive ribozyme. substrate complexes.
      Reaction rates for cleavage, ligation, and substrate binding to both ribozyme
      conformations were determined. Ligation rates (3 min-1) were typically 15-fold
      greater than cleavage rates (0.2 min-1), demonstrating that the hairpin ribozyme
      is an efficient RNA ligase. On the other hand, substrate binding is very rapid
      (kon = 4 x 10(8) M-1 min-1), and the ribozyme. substrate complex is very stable
      (KD < 25 pM; koff < 0.01 min-1). Stabilization of helix 4 increases the
      proportion of RNA molecules folded into the active conformation, and enhances
      substrate association and ligation rates. These effects can be explained by
      stabilization of the catalytic core of the ribozyme. Rigorous consideration of
      conformational isomers and their intrinsic kinetic properties was necessary for
      development of a kinetic scheme for the ribozyme-catalyzed reaction.

PMID- 9153213
TI  - Accessory subunit of mitochondrial DNA polymerase from Drosophila embryos.
      Cloning, molecular analysis, and association in the native enzyme.
AB  - A full-length cDNA of the accessory (beta) subunit of mitochondrial DNA
      polymerase from Drosophila embryos has been obtained, and its nucleotide sequence
      was determined. The cDNA clone encodes a polypeptide with a deduced amino acid
      sequence of 361 residues and a predicted molecular mass of 41 kDa. The gene
      encoding the beta subunit lies within 4 kilobase pairs of that for the catalytic
      subunit in the Drosophila genome, on the left arm of chromosome 2. The two genes
      have similar structural features and share several common DNA sequence elements
      in their upstream regions, suggesting the possibility of coordinate regulation. A
      human cDNA homolog of the accessory subunit was identified, and its nucleotide
      sequence was determined. The human sequence encodes a polypeptide with a
      predicted molecular mass of 43 kDa that shows a high degree of amino acid
      sequence similarity to the Drosophila beta subunit. Subunit-specific rabbit
      antisera, directed against the recombinant catalytic and accessory subunit
      polypeptides overexpressed and purified from Escherichia coli, recognize
      specifically and immunoprecipitate the native enzyme from Drosophila embryos.
      Demonstration of the physical association of the two subunits in the Drosophila
      enzyme and identification of a human accessory subunit homolog provide evidence
      for a common heterodimeric structure for animal mitochondrial DNA polymerases.

PMID- 9153214
TI  - Potassium transport by amino acid permeases in Saccharomyces cerevisiae.
AB  - Deletion of the potassium transporter genes TRK1 and TRK2 impairs potassium
      uptake in Saccharomyces cerevisiae, resulting in a greatly increased requirement
      for the ion and the inability to grow on low pH medium. Selection for mutations
      that restored growth of trk1Delta trk2Delta cells on low pH (3.0) medium led to
      the isolation of a dominant suppressor that also partially suppressed the
      increased K+ requirement of these cells. Molecular analysis revealed the
      suppressor to be an allele of BAP2 that encodes a permease for branched chain
      amino acids. The suppressor mutation (BAP2-1) converts a phenylalanine codon,
      highly conserved among the amino acid permease genes, to a serine codon in a
      region predicted to lie within the sixth membrane-spanning domain. Generation of
      the analogous mutation in the histidine permease produced an allele, HIP1-293,
      that similarly suppressed the low pH sensitivity of trk1Delta trk2Delta cells.
      Suppression of trk1Delta trk2Delta phenotypes by BAP2-1 or HIP1-293 was
      correlated with increased Rb+ uptake. The presence of the substrate amino acids
      enhanced but was not essential for suppression of trk1Delta trk2Delta phenotypes
      and increased Rb+ uptake. The conserved site altered by the suppressor mutations
      appears to be important; his4 HIP1-293 cells show an increased requirement for
      histidine compared with his4 HIP1 cells.

PMID- 9153215
TI  - Cytosolic alkalinization increases stress-activated protein kinase/c-Jun NH2
      terminal kinase (SAPK/JNK) activity and p38 mitogen-activated protein kinase
      activity by a calcium-independent mechanism.
AB  - Stress-activated protein kinases (SAPK) are stimulated by a variety of agents and
      conditions that also activate the Na+/H+ exchanger (NHE). Activation of the
      exchanger results in a rapid increase in intracellular pH (pHi), raising the
      possibility that cytosolic alkalinization may contribute to SAPK activation. This
      hypothesis was tested by manipulating the pHi of U937 cells using permeant weak
      bases. Three different bases increased pHi and caused a 4-12-fold increase in
      SAPK activity with a time course that paralleled intracellular alkalinization.
      p38, a related stress kinase, was also stimulated by the weak bases. Stimulation
      of the stress kinases was not accompanied by changes in cytosolic free calcium
      nor was the activation of SAPK achieved when calcium was elevated by thapsigargin
      or calcium ionophores. Weak bases not only alter the pH of the cytosol but also
      alkalinize endomembrane compartments such as endosomes and lysosomes. However,
      the latter do not appear to mediate the stimulation of SAPK, since neither
      bafilomycin A1 nor desipramine, agents that neutralize acidic endomembrane
      compartments, activated the kinase. Because hyperosmolarity acutely activates the
      NHE, we considered whether the resulting cytosolic alkalinization mediates the
      activation of SAPK upon cell shrinkage. The addition of amiloride or the omission
      of Na+, which were verified to inhibit NHE, did not prevent the osmotically
      induced activation of SAPK. We conclude that cytosolic alkalinization increases
      the activity of SAPK and p38 by a calcium-independent mechanism that does not
      involve acidic intracellular organelles. In addition, even though cell shrinkage
      is accompanied by alkalinization due to the activation of NHE, the increased pHi
      is not the main cause of the observed stimulation of SAPK upon hyperosmotic
      challenge.

PMID- 9153216
TI  - SecE-depleted membranes of Escherichia coli are active. SecE is not obligatorily
      required for the in vitro translocation of certain protein precursors.
AB  - Membrane vesicles were prepared from Escherichia coli cells in which SecE was
      depleted to 2% of wild-type membranes. SecE depletion had pleiotropic effects;
      SecD, SecF, SecG, and SecY were decreased 4-6-fold, whereas SecA was increased
      about 16-fold over that of wild-type membranes. These membranes were
      substantially active in the in vitro translocation of proOmpA, which was mediated
      by the SecA pathway since it was inhibited by azide. Similar substantial
      translocation activities were observed for proLamB and proLpp in the SecE
      depleted membranes. However, the translocation of proPhoA was more severely
      impaired. These data indicate that SecE may enhance but is not obligatorily
      required for the translocation of at least certain precursors, and suggest that
      the effects of the SecE depletion on protein translocation may be precursor
      dependent.

PMID- 9153217
TI  - Functional evaluation of the structural features of proteases and their substrate
      in fibrin surface degradation.
AB  - A new model has been introduced to characterize the action of a fluid phase
      enzyme on a solid phase substrate. This approach is applied to evaluate the
      kinetics of fibrin dissolution with several proteases. The model predicts the
      rate constants for the formation and dissociation of the protease-fibrin complex,
      the apparent order of the association reaction between the enzyme and the
      substrate, as well as a global catalytic constant (kcat) for the dissolution
      process. These kinetic parameters show a strong dependence on the nature of the
      applied protease and on the structure of the polymerized substrate. The kinetic
      data for trypsin, PMN-elastase, and three plasminogen-derived proteases with
      identical catalytic domain, but with a varied N-terminal structure, are compared.
      The absence of kringle5 in des-kringle1-5-plasmin (microplasmin) is related to a
      markedly lower kcat (0.008 s-1) compared with plasmin and des-kringle1-4plasmin
      (miniplasmin) (0.039 s-1). The essentially identical kinetic parameters for
      miniplasmin and plasmin with the exception of kdiss, which is higher for
      miniplasmin (81.8 s-1 versus 57.6 s-1), suggest that the first four kringle
      domains are needed to retain the enzyme in the enzyme-fibrin complex. Trypsin, a
      protease of similar primary specificity to plasmin, but with a different
      catalytic domain, shows basically the same kcat as plasmin, but its affinity to
      fibrin is markedly lower compared with plasmin and even microplasmin. The latter
      suggests that in addition to the kringle domains, the structure of the catalytic
      domain in plasmin also contributes to its specificity for fibrin. The thinner and
      extensively branched fibers of fibrin are more efficiently dissolved than the
      fibers with greater diameter and lower number of branching points. When the
      polymer is stabilized through covalent cross-linking, the kcat for plasmin and
      miniplasmin is 2-4-fold higher than on non-cross-linked fibrin, but the decrease
      in the association rate constant for the formation of enzyme-substrate complex
      explains the relative proteolytic resistance of the cross-linked fibrin. Thus,
      the functional evaluation of the discrete steps of the fibrinolytic process
      reveals new aspects of the interactions between proteases and their polymer
      substrate.

PMID- 9153218
TI  - Organ-specific transcription of the rrn operon in spinach plastids.
AB  - The spinach rrn operon is used as a model system to study transcriptional
      regulation in higher plant photosynthetic and non-photosynthetic plastids. We
      performed capping experiments to determine whether P1, PC, or P2 promoters are
      employed for rrn transcription start sites in cotyledon and root tissues. By
      using a new method of analysis of capped RNA we demonstrate for the first time
      that 1) in both organs the rrn operon is expressed in a constitutive manner by
      cotranscription with the preceding tRNA(GAC)Val gene, and 2) the PC transcription
      start site is used only in cotyledons and leaves, i.e. we demonstrate the organ
      specific usage of a plastid promoter. Both start sites, PC and that of the
      tRNA(GAC)Val cotranscript, lack Escherichia coli-like consensus sequences. The
      cotranscript is initiated 457 base pairs upstream of the tRNA(GAC)Val gene. The
      PC-specific DNA-binding factor, CDF2, is not detectable in root tissues
      confirming its regulatory role in PC-initiated rrn expression and the organ
      specificity of PC expression. Furthermore, our results show that rrn operon
      expression patterns differ in spinach and tobacco indicating species-specific
      transcriptional regulation of plant plastid gene expression.

PMID- 9153219
TI  - Lysophosphatidylcholine stimulates activator protein 1 and the c-Jun N-terminal
      kinase activity.
AB  - Lysophosphatidylcholine (lyso-PC), a natural lipid generated through the action
      of phospholipase A2 on membrane phosphatidylcholine, has been implicated in
      atherogenesis and the inflammatory process. In vitro studies have established a
      role for lyso-PC in modulation of gene expression and other cellular responses
      including differentiation and proliferation. There is also evidence that lyso-PC
      may act as an intracellular second messenger transducing signals elicited from
      membrane-associated receptors. The mechanisms behind the diverse activities of
      lyso-PC are poorly understood. We report, in this study, that treatment of
      cultured cells with exogenous lyso-PC, at nontoxic concentrations, potently
      induced activator protein-1 (AP-1) DNA binding and transcriptional activity
      independent of well known AP-1 activators, protein kinase C or mitogen-activated
      protein kinases ERK1 and ERK2. Lyso-PC also activated the c-Jun N-terminal kinase
      (JNK/SAPK), a recently characterized member of the mitogen-activated protein
      kinase family, known to activate AP-1. The stimulated JNK and AP-1 activities
      probably mediate or contribute to some bioactive effects of lyso-PC.

PMID- 9153220
TI  - Characterization of functional domains within Smad4/DPC4.
AB  - Smad proteins are a family of highly conserved, intracellular proteins that
      signal cellular responses downstream of transforming growth factor-beta (TGF
      beta) family serine/threonine kinase receptors. One of these molecules, Smad4,
      originally identified as the candidate tumor suppressor gene dpc-4, reconstitutes
      TGF-beta- and activin-dependent transcriptional responses in Smad4 null cell
      lines and interacts in a ligand-dependent manner with other Smad family members
      in both TGF-beta, activin, and bone morphogenetic protein-2/-4 pathways. Here, we
      used an assay based on the restoration of ligand-dependent transcriptional
      responses in a Smad4 null cell line to characterize functional domain structures
      within Smad4. We showed that restoration of TGF-beta-induced transcriptional
      responses by Smad4 was inhibited by co-transfection with a kinase dead TGF-beta
      type II receptor and that constitutive activation was blocked with TGF-beta
      neutralizing antibodies, confirming the essential role of Smad4 in TGF-beta
      signaling. Using a series of Smad4 mutation, deletion, and Smad1/Smad4 chimera
      constructs we identified a 47-amino acid deletion within the middle-linker region
      of Smad4 that is essential for the mediation of signaling responses. In addition,
      we showed that the NH2-terminal domain of Smad4 augments ligand-dependent
      activation associated with the middle-linker region, indicating that there is a
      distinct ligand-response domain within the N terminus of this molecule.

PMID- 9153221
TI  - Interferon-gamma increases the sensitivity of islets of Langerhans for inducible
      nitric-oxide synthase expression induced by interleukin 1.
AB  - The purpose of this study was to evaluate the effects of interferon-gamma (IFN
      gamma) alone and in combination with interleukin 1beta (IL-1beta) on inducible
      nitric-oxide synthase (iNOS) mRNA and protein expression, nitrite production, and
      insulin secretion by islets of Langerhans. Treatment of rat islets with IL-1beta
      results in a concentration-dependent increase in the production of nitrite that
      is maximal at 5 units/ml. Individually, 0. 1 unit/ml IL-1beta or 150 units/ml rat
      IFN-gamma do not stimulate iNOS expression or nitrite production by rat islets;
      however, in combination, these cytokines induce the expression of iNOS and the
      production of nitrite to levels similar in magnitude to the individual effects of
      5 units/ml IL-1beta. The islet beta-cell, selectively destroyed during insulin
      dependent diabetes mellitus, appears to be one islet cellular source of iNOS as
      150 units/ml rat IFN-gamma and 0.1 unit/ml IL-1beta induced similar effects in
      primary beta-cells purified by fluorescence-activated cell sorting and in the rat
      insulinoma cell line, RINm5F. iNOS expression and nitrite production by rat
      islets in response to 150 units/ml rat IFN-gamma and 0.1 unit/ml IL-1beta are
      correlated with an inhibition of insulin secretion and islet degeneration that
      are prevented by the iNOS inhibitor aminoguanidine. The mechanism by which IFN
      gamma increases the sensitivity of beta-cells for IL-1-induced iNOS expression
      appears to be associated with an increase in the stability of iNOS mRNA. Last,
      cellular damage during physical dispersion of islets results in the release of
      sufficient amounts of IL-1beta to induce iNOS expression and nitrite production
      in the presence of exogenously added rat IFN-gamma. The cellular source of IL
      1beta under these conditions is believed to be resident islet macrophages as
      depletion of macrophages prior to dispersion prevents IFN-gamma-induced iNOS
      expression and nitrite formation by dispersed islet cells. These studies show
      that the T-lymphocyte cytokine, IFN-gamma, increases the sensitivity of rat
      islets to the effects of IL-1beta on iNOS expression and nitrite production by 10
      fold, in part, through the stabilization of iNOS mRNA. Our studies also support
      an effector role for IFN-gamma, in concert with resident islet macrophage release
      of IL-1beta, in mediating beta-cell destruction during the development of
      autoimmune diabetes.

PMID- 9153222
TI  - The cell adhesion domain in plasma vitronectin is cryptic.
AB  - Vitronectin (Vn) is a major adhesive glycoprotein in blood. However, many of the
      functions of Vn are regulated by its conformational state and degree of
      multimerization. Here, the ability of native and denatured Vn to bind to integrin
      adhesion receptors was compared. Three lines of evidence suggest that the native,
      plasma form of Vn is not an adhesive glycoprotein. (i) Antibodies that bind in
      close proximity to the cell adhesion domain of Vn fail to bind to native Vn
      present in unfractionated plasma. (ii) Denatured Vn binds to both glycoprotein
      IIb/IIIa and alphavbeta3 in a dose-dependent manner. In contrast, native Vn is
      unable to bind either integrin. (iii) Thermal denaturation of native Vn, or its
      complexation with type 1 plasminogen activator inhibitor, exposed the cell
      adhesion domain of Vn. Thus, while plasma Vn is unable to bind integrins and is
      not an adhesive glycoprotein, the conformationally altered from of the protein
      binds avidly to both alphavbeta3 and glycoprotein IIb/IIIa. The data presented
      here indicate that such conformational changes in Vn are likely to occur in areas
      of tissue injury and thrombosis.

PMID- 9153223
TI  - All-trans-retinoic acid increases transforming growth factor-beta2 and insulin
      like growth factor binding protein-3 expression through a retinoic acid receptor
      alpha-dependent signaling pathway.
AB  - Retinoids, including retinol and retinoic acid derivatives, maintain the normal
      growth and differentiation of human bronchial epithelial cells. The signaling
      pathways through which retinoids mediate these effects have not been defined.
      Insulin-like growth factor binding protein-3 (IGFBP-3) and the transforming
      growth factor-beta (TGF-beta) gene family (beta1-3) were examined as potential
      components of the retinoid signaling pathway in normal human bronchial epithelial
      cells. All-trans-retinoic acid (t-RA) increased the levels of TGF-beta2 and IGFBP
      3 mRNA and of secreted TGF-beta and IGFBP-3 proteins. An antagonist of retinoic
      acid receptor-alpha, LG100629, abrogated the increase in TGF-beta2 and IGFBP-3
      mRNA levels induced by t-RA. t-RA increased IGFBP-3 mRNA levels transiently from
      1 to 6 h, and subsequently a sustained increase began at 72 h, which coincided
      with the appearance of active TGF-beta in the media. Treatment with TGF-beta2
      increased IGFBP-3 mRNA levels, but treatment with latency-associated peptide,
      which inactivates secreted TGF-beta, did not abrogate the effect of t-RA on IGFBP
      3 expression. These findings provide evidence that t-RA increased TGF-beta2 and
      IGFBP-3 expression through an retinoic acid receptor-alpha-dependent pathway, and
      the increase in IGFBP-3 expression by t-RA did not require activation of the TGF
      beta pathway by autocrine or paracrine mechanisms.

PMID- 9153224
TI  - Raf-1 kinase and exoenzyme S interact with 14-3-3zeta through a common site
      involving lysine 49.
AB  - 14-3-3 proteins are a family of conserved dimeric molecules that bind to a range
      of cellular proteins involved in signal transduction and oncogenesis. Our
      solution of the crystal structure of 14-3-3zeta revealed a conserved amphipathic
      groove that may allow the association of 14-3-3 with diverse ligands (Liu, D.,
      Bienkowska, J., Petosa, C., Collier, R. J., Fu, H., and Liddington, R. (1995)
      Nature 376, 191-194). Here, the contributions of three positively charged
      residues (Lys-49, Arg-56, and Arg-60) that lie in this Raf-binding groove were
      investigated. Two of the charge-reversal mutations greatly (K49E) or partially
      (R56E) decreased the interaction of 14-3-3zeta with Raf-1 kinase, whereas R60E
      showed only subtle effects on the binding. Interestingly, these mutations
      exhibited similar effects on the functional interaction of 14-3-3zeta with
      another target protein, exoenzyme S (ExoS), an ADP-ribosyltransferase from
      Pseudomonas aeruginosa. The EC50 values of 14-3-3zeta required for ExoS
      activation increased by approximately 110-, 5-, and 2-fold for the K49E, R56E,
      and R60E mutants, respectively. The drastic reduction of 14-3-3zeta/ligand
      affinity by the K49E mutation is due to a local electrostatic effect, rather than
      the result of a gross structural alteration, as evidenced by partial proteolysis
      and circular dichroism analysis. This work identifies the first point mutation
      (K49E) that dramatically disrupts 14-3-3zeta/ligand interactions. The parallel
      effects of this single point mutation on both Raf-1 binding and ExoS activation
      strongly suggest that diverse associated proteins share a common structural
      binding determinant on 14-3-3zeta.

PMID- 9153225
TI  - The winged helix transcriptional activator HFH-3 is expressed in the distal
      tubules of embryonic and adult mouse kidney.
AB  - The hepatocyte nuclear factor-3 (HNF-3)/fork head homolog (HFH) proteins are an
      extensive family of transcription factors, which share homology in the winged
      helix DNA binding domain. Members of the HFH/winged helix family have been
      implicated in cell fate determination during pattern formation, in organogenesis,
      and in cell-type-specific gene expression. In this study we isolated a full
      length HFH-3 cDNA clone from a human kidney library which encoded a 351-amino
      acid protein containing a centrally located winged helix DNA binding domain. We
      demonstrate that HFH-3 is a potent transcriptional activator requiring 138 C
      terminal residues for activity. We used in situ hybridization to demonstrate that
      HFH-3 expression is restricted to the epithelium of the renal distal convoluted
      tubules. We determined the HFH-3 DNA binding consensus sequence by in vitro DNA
      binding site selection using recombinant HFH-3 protein and used this consensus
      sequence to identify putative HFH-3 target genes expressed there. These putative
      HFH-3 target genes include the Na/K-ATPase, Na/H and anion exchangers, E
      cadherin, and mineralocorticoid receptor genes as well as genes for the
      transcription factors HNF-1, vHNF-1, and HNF-4.

PMID- 9153226
TI  - Mammalian GADD34, an apoptosis- and DNA damage-inducible gene.
AB  - The mammalian cellular response to genotoxic stress is a complex process
      involving many known and probably many as yet unknown genes. Induction of the
      human DNA damage- and growth arrest-inducible gene, GADD34, by ionizing radiation
      was only seen in certain cell lines and correlated with apoptosis following
      ionizing radiation. In addition, the kinetics and dose response of GADD34 to
      ionizing radiation closely paralleled that of the apoptosis inhibitor, BAX.
      However, unlike BAX, the GADD34 response was independent of cellular p53 status.
      The carboxyl terminus of GADD34 has homology with the carboxyl termini of two
      viral proteins, one of which is known to prevent apoptosis of virus infected
      cells. The association of GADD34 expression with certain types of apoptosis and
      its homology with a known apoptosis regulator suggests that GADD34 may play a
      role in apoptosis as well.

PMID- 9153227
TI  - Two eye guanylyl cyclases are expressed in the same photoreceptor cells and form
      homomers in preference to heteromers.
AB  - We recently described two eye guanylyl cyclases (GC-E and GC-F) that contain an
      apparent extracellular domain potentially capable of binding ligands (Yang, R.
      B., Foster, D. C., Garbers, D. L., and Fulle, H.-J. (1995) Proc. Natl. Acad. Sci.
      U. S. A. 92, 602-606). Here, Northern and Western analyses showed that both
      cyclases are expressed in the retina and enriched in photoreceptor outer
      segments. By the use of specific GC-E and GC-F antibodies coupled to different
      sized gold particles both cyclases were colocalized within the same photoreceptor
      cells raising the possibility of homomeric and/or heteromeric interactions. A
      point mutant of GC-E (D878A) was constructed and expressed; it contained no
      detectable cyclase activity but acted in a dominant negative fashion to abolish
      the activity of native GC-E and GC-F in coexpression studies. These results
      suggested that GC-E and GC-F could form either homomers or heteromers, at least
      when overexpressed in COS-7 cells. Immunoprecipitation with GC-E and GC-F
      antibody followed by Western analysis confirmed that both homomers and heteromers
      could be formed. However, similar experiments using retina or outer segments
      revealed that a vast majority of GC-E and GC-F were precipitated as homomers in
      the eye. Therefore, like other members of the membrane guanylyl cyclase
      subfamily, GC-E and GC-F appear to preferentially form homomers.

PMID- 9153228
TI  - Isolation and characterization of a new member of the scavenger receptor
      superfamily, glycoprotein-340 (gp-340), as a lung surfactant protein-D binding
      molecule.
AB  - We have purified a previously unknown glycoprotein (designated gp-340) from human
      bronchioalveolar lung washings from a patient with alveolar proteinosis. gp-340
      was identified by its calcium-dependent binding to lung surfactant protein D (SP
      D) and by its molecular mass of 340 kDa in the reduced state on SDS
      polyacrylamide gel electrophoresis (PAGE). gp-340 was purified from the 10,000 x
      g pellet of the lavage fluid by ion-exchange and gel permeation chromatography.
      On SDS-PAGE, gp-340 showed an apparent molecular mass of 290 kDa in the unreduced
      state. On gel chromatography under non-dissociating conditions, the apparent
      molecular mass of gp-340 was >1000 kDa. The presence of N-linked glycosylation
      was shown by digestion with N-glycosidase F, which reduced the apparent molecular
      mass of gp-340 under reducing condition to about 300 kDa. Partial amino acid
      sequence data showed the presence of scavenger-receptor type domains. Monoclonal
      and polyclonal antibodies were raised against gp-340, and their specificities
      were confirmed by Western blotting. The antibodies were used for
      immunohistochemical localization of gp-340 in the lung, where it was found on the
      surface of and within alveolar macrophages. Direct binding between gp-340 and SP
      D took place at physiological ionic strength, required the presence of calcium,
      and was not inhibited by maltose. The binding between SP-D and mannan also
      required the presence of calcium, but this interaction was completely inhibited
      by maltose. The same binding pattern was seen between gp-340 and recombinant
      human SP-D composed of the trimeric neck region and three carbohydrate
      recognition domains. These findings indicate that the binding between gp-340 and
      SP-D is a protein-protein interaction rather than a lectin-carbohydrate
      interaction and that the binding to gp-340 takes place via the carbohydrate
      recognition domain of SP-D. We conclude that gp-340 is a new member of the
      scavenger-receptor superfamily and likely to be a truncated form of a receptor
      for SP-D.

PMID- 9153229
TI  - The N-terminal domain of human GABA receptor rho1 subunits contains signals for
      homooligomeric and heterooligomeric interaction.
AB  - gamma-Aminobutyric acid type C (GABAC) receptors identified in retina appear to
      be composed of GABA rho subunits. The purpose of this study was to localize
      signals for homooligomeric assembly of rho1 subunits and to investigate whether
      the same region contained signals for heterooligomeric interaction with rho2
      subunits. In vitro translated human rho1 was shown to be membrane-associated, and
      proteinase K susceptibility studies indicated that the N terminus was oriented in
      the lumen of ER-derived microsomal vesicles. This orientation suggested the
      involvement of the N terminus of rho1 in the initial steps of subunit assembly.
      To test this hypothesis, mutants were created containing only N-terminal
      sequences (N-rho1) or C-terminal sequences (C-rho1) of rho1. Co
      immunoprecipitation studies revealed that N-rho1, but not C-rho1, interacted with
      rho1 in vitro. When coexpressed in Xenopus oocytes, N-rho1 interfered with rho1
      receptor formation. Together, these data suggested that signals for rho1
      homooligomeric assembly reside in the N-terminal half of the subunit. Sequential
      immunoprecipitations were then performed upon cotranslated rho1 and rho2 subunits
      which demonstrated that rho1 and rho2 interacted in vitro. Co-immunoprecipitation
      indicated that N-rho1 specifically associated with rho2. Therefore, the N
      terminal regions of rho subunits contain the initial signals for both
      homooligomeric and heterooligomeric assembly into receptors with GABAC
      properties.

PMID- 9153230
TI  - Analysis of the methylation pattern of the maize opaque-2 (O2) promoter and in
      vitro binding studies indicate that the O2 B-Zip protein and other endosperm
      factors can bind to methylated target sequences.
AB  - The maize opaque-2 locus (o2) has an endosperm-specific expression and is
      positively autoregulated by its gene product, a b-Zip protein, to a TGACGTTG
      motif. The genomic sequencing method was used here to describe, in leaf and
      endosperm, the methylation pattern of a 390-base pair region of the o2 promoter.
      In leaf, 96% of the C residues are methylated, whereas in endosperm the 5
      methylcytosine content is 84%. Comparison of these methylation patterns indicates
      that the o2 tissue-specific expression does not result from the demethylation of
      any specific C residue and that, in vivo, O2 interacts with a methylated target
      sequence. Consistently, gel-shift experiments using a CpG-methylated, partially
      methylated, and hemimethylated o2 promoter fragments showed that, in vitro, the
      O2 protein binds to the major groove of a methylated target sequence, although
      its binding activity decreases at increasing levels of C-methylation and is more
      effectively reduced by methylation of the lower strand than of the upper strand
      of the DNA. Using partially purified endosperm cell extracts, we also show that,
      besides the O2 protein, other proteins specifically bind to a partially
      methylated o2 promoter fragment, therefore indicating that in plants a subset of
      different proteins may mediate the expression of a naturally occurring methylated
      o2 promoter.

PMID- 9153231
TI  - Cell cycle-dependent expression and spindle pole localization of a novel human
      protein kinase, Aik, related to Aurora of Drosophila and yeast Ipl1.
AB  - Mutations in Aurora of Drosophila and related Saccharomyces cerevisiae Ipl1
      kinase are known to cause abnormal chromosome segregation. We have isolated a
      cDNA encoding a novel human protein kinase of 402 amino acids with a predicted
      molecular mass of 45.9 kDa, which shares high amino acid identities with the
      Aurora/Ipl1 protein kinase family; hence the cDNA is designated as aik
      (aurora/IPL1-related kinase). Amino acid sequence of C-terminal kinase domain of
      Aik shares 86, 86, 72, 59, and 49% identity with those of Xenopus XLP46APK and
      XLP46BPK, mouse STK-1, Aurora of Drosophila, and yeast Ipl1, respectively,
      whereas N-terminal domain of Aik shares high homology only with those of XLP46APK
      and XLP46BPK. Northern and Western blotting analyses revealed that Aik is
      expressed highly in testis and various proliferating cells including HeLa cells.
      In HeLa cells, the endogenous levels of aik mRNA and protein contents are tightly
      regulated during cell cycle progression. Both of these levels are low in G1/S,
      accumulate during G2/M, and reduce rapidly after mitosis. Its protein kinase
      activity is also enhanced at mitosis as inferred by exogenous casein
      phosphorylation. Immunofluorescence studies using a specific antibody have shown
      that Aik is localized to the spindle pole during mitosis, especially from
      prophase through anaphase. These results strongly suggest that Aik is a novel
      member of a protein kinase family possibly involved in a centrosome function(s)
      such as chromosome segregation or spindle formation.

PMID- 9153232
TI  - Purification and cloning of carp nephrosin, a secreted zinc endopeptidase of the
      astacin family.
AB  - We have purified a secreted proteinase of 23 kDa from carp head kidney by
      sequential column chromatography on a Reactive Blue 72-agarose dye affinity
      column and an FPLC Mono-P column. The secretion of this proteinase from carp head
      kidney can be stimulated by high concentrations of potassium. Since the carp
      proteinase is present mainly in the head kidney, kidney, and spleen (all of which
      are lymphohematopoietic organs), it is named nephrosin. The carp nephrosin is
      most sensitive to metal chelators, but not to inhibitors specific for other
      classes of proteinases. A cDNA clone has been isolated from a carp head kidney
      cDNA library by immunoscreening with a polyclonal antiserum raised against
      purified nephrosin. The cloned cDNA is 1086 base pairs in length and has an open
      reading frame encoding a protein of 273 amino acids, including a 19-amino acid
      signal peptide and 56-amino acid propeptide. The deduced amino acid sequence
      shows moderate levels of identity to medaka HCE1 (52.5%), medaka LCE (50.7%),
      crayfish astacin (33.2%), murine meprin-alpha (34%), and murine meprin-beta
      (33.5%), all members of the astacin family of zinc endopeptidases. Nephrosin is
      the first member of the astacin family found in lymphohematopoietic tissues.

PMID- 9153233
TI  - Binding of HIV-1 Nef to a novel thioesterase enzyme correlates with Nef-mediated
      CD4 down-regulation.
AB  - Nef is a 27-kDa myristoylated protein conserved in primate lentiviruses. In vivo,
      simian immunodeficiency virus Nef is required in macaques to produce a high viral
      load and full pathological effects. Nef has at least three major effects in
      vitro, induction of CD4 down-regulation, alteration of T cell activation
      pathways, and enhancement of viral infectivity. We have used the yeast two-hybrid
      system to identify cellular proteins that interact with HIV-1Lai Nef and could
      mediate Nef function. A human cDNA was isolated that encodes a new type of
      thioesterase, an enzyme that cleaves thioester bonds. This novel thioesterase is
      unlike the animal types I and II thioesterases previously cloned but is
      homologous to the Escherichia coli thioesterase II. Nef and this thioesterase
      interact in vitro and are co-immunoprecipitated by anti-Nef antibodies in CEM
      cells expressing Nef. Nef alleles from human immunodeficiency virus-1 (HIV-1)
      isolates unable to down-regulate CD4 do not react or react poorly with
      thioesterase. An HIV-1 NefLai mutant selected for its lack of interaction with
      thioesterase was also unable to down-regulate CD4 cell-surface expression. These
      observations suggest that this human thioesterase is a cellular mediator of Nef
      induced CD4 down-regulation.

PMID- 9153234
TI  - The yeast Fre1p/Fre2p cupric reductases facilitate copper uptake and are
      regulated by the copper-modulated Mac1p activator.
AB  - Fre1p and Fre2p are ferric reductases which account for the total plasma membrane
      associated activity, a prerequisite for iron uptake, in Saccharomyces cerevisiae.
      The two genes are transcriptionally induced by iron depletion. In this
      communication, we provide evidence that Fre2p has also cupric reductase activity,
      as has been previously shown for Fre1p (Hassett, R., and Kosman, D.J. (1995) J.
      Biol. Chem. 270, 128-134). Both Fre1p and Fre2p enzymes are functionally
      significant for copper uptake, as monitored by the accumulation of the copper
      regulated CUP1 and CTR1 mRNAs in fre1Delta, fre2Delta, and fre1Deltafre2Delta
      mutant strains. However, only Fre1p activity is induced by copper depletion, even
      in the presence of iron. This differential copper-dependent regulation of Fre1p
      and Fre2p is exerted at the transcriptional level of the two genes. We have shown
      that Mac1p, known to affect the basal levels of FRE1 gene expression (Jungmann,
      J., Reins, H.-A., Lee, J., Romeo, A., Hassett, R., Kosman, D., and Jentsch, S.
      (1993) EMBO J. 12, 5051-5056), accounts for both the copper-dependent induction
      of FRE1 and down-regulation of FRE2 gene. Finally, Mac1p transcriptional
      activation function is itself modulated by the availability of copper.

PMID- 9153235
TI  - Flotillin and epidermal surface antigen define a new family of caveolae
      associated integral membrane proteins.
AB  - Caveolae are plasmalemmal microdomains that are involved in vesicular trafficking
      and signal transduction. We have sought to identify novel integral membrane
      proteins of caveolae. Here we describe the identification and molecular cloning
      of flotillin. By several independent methods, flotillin behaves as a resident
      integral membrane protein component of caveolae. Furthermore, we have identified
      epidermal surface antigen both as a flotillin homologue and as a resident
      caveolar protein. Significantly, flotillin is a marker for the Triton-insoluble,
      buoyant membrane fraction in brain, where to date mRNA species for known caveolin
      gene family members have not been detected.

PMID- 9153236
TI  - Molecular cloning of a novel human CC chemokine EBI1-ligand chemokine that is a
      specific functional ligand for EBI1, CCR7.
AB  - By searching the expressed sequence tag (EST) data base, we identified partial
      cDNA sequences encoding a novel human CC chemokine. We determined the complete
      cDNA sequence that encodes a highly basic polypeptide of a total 98 amino acids
      with 20 to 30% identity to other human CC chemokines. We termed this novel
      chemokine from EBI1-Ligand Chemokine as ELC (see below). The ELC mRNA was most
      strongly expressed in the thymus and lymph nodes. Recombinant ELC protein was
      expressed as a fusion protein with the Flag tag (ELC-Flag). For receptor-binding
      assays, recombinant ELC protein fused with the secreted form of alkaline
      phosphatase (SEAP) was used. By stably expressing five CC chemokine receptors
      (CCR1 to 5) and five orphan receptors, ELC-SEAP was found to bind specifically to
      an orphan receptor EBI1. Only ELC-Flag, but not MCP-1, MCP-2, MCP-3, eotaxin, MIP
      1alpha, MIP-1beta, RANTES (regulated on activation normal T cell expressed and
      secreted), thymus and activation-regulated chemokine (TARC), or liver and
      activation-regulated chemokine (LARC), competed with ELC-SEAP for EBI1. ELC-Flag
      induced transient calcium mobilization and chemotactic responses in EBI1
      transfected cells. ELC-Flag also induced chemotaxis in HUT78 cells expressing
      endogenous EBI1 at high levels. By somatic hybrid and radiation hybrid analyses,
      the gene for ELC (SCYA19) was mapped to chromosome 9p13 instead of chromosome
      17q11.2 where the genes for CC chemokines are clustered. Taken together, ELC is a
      highly specific ligand for EBI1, which is known to be expressed in activated B
      and T lymphocytes and strongly up-regulated in B cells infected with Epstein-Barr
      virus and T cells infected with herpesvirus 6 or 7. ELC and EBI1 may thus play
      roles in migration and homing of normal lymphocytes, as well as in
      pathophysiology of lymphocytes infected with these herpesviruses. We propose EBI1
      to be designated as CCR7.

PMID- 9153237
TI  - Uncoupling of ligand-binding affinity of the bacterial serine chemoreceptor from
      methylation- and temperature-modulated signaling states.
AB  - The Escherichia coli chemoreceptor Tsr mediates tactic responses to serine,
      repellents, and changes in temperature. We have previously shown that the serine
      sensing ability of Tsr-T156C, which has a unique cysteine in place of threonine
      at residue 156, is specifically inactivated by thiol-modifying reagents and that
      L-serine protects the receptor from modification. In this study, we demonstrated
      the correlation between protective effects of various attractants and their
      potencies to elicit attractant responses. This indirect binding assay was used to
      monitor the affinity of the receptor for L-serine under various conditions. It
      has been demonstrated by in vitro assays that the ligand-binding affinities of
      Tsr and the related chemoreceptor Tar are unaffected by changes in the
      methylation state of the receptor. Using the serine protection assay, we re
      examined this issue both in vitro and in vivo. The methylation levels of Tsr
      T156C did not affect its ligand-binding affinity. We also showed both in vitro
      and in vivo that the ligand-binding affinity was unaffected by temperature. These
      results suggest that the structure of the periplasmic domain of the receptor is
      uncoupled from the signaling states of the cytoplasmic domain. This ligand
      binding assay system should be applicable to other receptors.

PMID- 9153238
TI  - Protein kinase C delta inhibits the proliferation of vascular smooth muscle cells
      by suppressing G1 cyclin expression.
AB  - To elucidate the physiological role of protein kinase C (PKC) delta, a
      ubiquitously expressed isoform in vascular smooth muscle cells (VSMC), PKC delta
      was stably overexpressed in A7r5 cells, rat clonal VSMC. The [3H]thymidine
      incorporation in A7r5 overexpressed with PKC delta (DVs) was suppressed to 37.1
      +/- 16.3% (mean +/- S.D.) of the level in control or A7r5 transfected with vector
      alone (EVs). The reduction of [3H]thymidine incorporation was strongly correlated
      with overexpressed PKC levels. Moreover, transient transfection of a dominant
      negative mutant of PKC delta restored the reduced proliferation in DVs. Flow
      cytometry analysis demonstrated that DVs were arrested in the G0/G1 phase of the
      cell cycle. Expression of cyclins D1 and E and retinoblastoma protein
      phosphorylation were reduced, while the protein levels of p27 were elevated in
      DVs as compared with EVs. There were no significant differences in the expression
      of c-fos, c-jun, c-myc, cyclin D2, D3, cyclin-dependent kinase 2, cyclin
      dependent kinase 4, and p21 among the clones. We conclude that PKC delta inhibits
      the proliferation of VSMC by arresting cells in G1 via mainly inhibiting the
      expression of cyclin D1 and cyclin E.

PMID- 9153239
TI  - ARD-1 cDNA from human cells encodes a site-specific single-strand
      endoribonuclease that functionally resembles Escherichia coli RNase E.
AB  - The human ARD-1 (activator of RNA decay) cDNA sequence can rescue mutations in
      the Escherichia coli rne gene, which specifies the essential endoribonuclease
      RNase E, resulting in RNase E-like cleavages in vivo in rne-defective bacteria
      and in vitro in extracts isolated from these cells (Wang, M., and Cohen, S. N.
      (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 10591-10595). Recent studies indicate
      that the 13.3-kDa protein encoded by ARD-1 cDNA is almost identical to the
      carboxyl-terminal end of the bovine protein NIPP-1, a nuclear inhibitor of
      protein phosphatase 1; separate transcripts formed by alternative splicing are
      proposed to encode the discrete ARD-1 and combined ARD-1/NIPP-1 products (Van
      Eynde, A., Wera, S., Beullens, M. , Torrekens, S., Van Leuven, F., Stalmans, W.,
      and Bollens, M. (1995) J. Biol. Chem. 270, 28068-28074). Here we show that
      affinity column-purified protein encoded by human ARD-1 cDNA in E. coli is a site
      specific Mg2+-dependent endoribonuclease that binds in vitro to RNase E
      substrates, cleaves RNA at the same sites as RNase E, and, like RNase E,
      generates 5' phosphate termini at sites of cleavage. Our results indicate that
      the ARD-1 peptide can function as a ribonucleolytic analog of E. coli RNase E as
      well as a domain of the protein phosphatase inhibitor, NIPP-1.

PMID- 9153240
TI  - Nonionic detergents induce dimerization among members of the Bcl-2 family.
AB  - Members of the Bcl-2 family (including Bcl-2, Bcl-XL, and Bax) play key roles in
      the regulation of apoptosis. These proteins are believed to be membrane
      associated and have been proposed to regulate apoptosis through both
      homodimerization and heterodimerization. We have found that whereas Bcl-2 is
      predominantly membrane-associated as previously reported, significant amounts of
      Bcl-XL and most of the Bax proteins are not membrane-associated and thus appear
      in the cytosolic fraction of thymocyte and splenocyte extracts. This finding
      allows the study of the dimerization properties and conformation of these
      proteins in the absence of detergent perturbation. For this analysis, we have
      produced monoclonal antibodies that are specific for known epitopes of Bax, Bcl
      2, and Bcl-XL. An antibody to an N-terminal epitope (alpha uBax 6A7) between
      amino acids 12 and 24 fails to bind the soluble cytosolic form of Bax, indicating
      that this epitope is normally buried. Nonionic detergents alter the Bax
      conformation to expose this epitope. In the presence of nonionic detergent, the
      6A7 antibody avidly binds the monomeric form of Bax, but not Bax complexed with
      either Bcl-XL or Bcl-2. In contrast, a monoclonal antibody to an adjacent epitope
      of Bax (alpha mBax 5B7) within amino acids 3-16 binds the soluble and detergent
      altered forms of Bax and also binds the Bax.Bcl-XL or the Bax.Bcl-2 complex.
      Surprisingly, in the absence of detergent Bax fails to form homodimers or
      heterodimers with Bcl-XL. These results demonstrate a novel conformational state
      of members of the Bcl-2 family under a physiological condition that is distinct
      from the detergent-altered state that forms dimers and is currently believed to
      regulate apoptosis.

PMID- 9153241
TI  - A novel role of follistatin, an activin-binding protein, in the inhibition of
      activin action in rat pituitary cells. Endocytotic degradation of activin and its
      acceleration by follistatin associated with cell-surface heparan sulfate.
AB  - There are two types of the activin-binding protein follistatin (FS), FS-288 and
      FS-315. These result from alternative splicing of mRNA. FS-288 exhibits high
      affinity for cell-surface heparan sulfate proteoglycans, whereas FS-315 shows low
      affinity. To understand the physiological role of cell-associated FS, we
      investigated the binding of activin to cell-associated FS and its behavior on the
      cell surface using primary cultured rat pituitary cells. Affinity cross-linking
      experiments using 125I-activin A demonstrated that activin bound to rat pituitary
      cells via FS as well as to their receptors on the cell surface. FS-288 promoted
      the binding of activin A to the cell surface more markedly than FS-315. When the
      cells were incubated with 125I-activin A in the presence of FS-288, significant
      degradation of activin A was observed, and this was dependent on the FS-288
      concentration. This activin degradation was abolished by heparan sulfate,
      chloroquine, and several lysosomal enzyme inhibitors. Moreover, FS-288 stimulated
      cellular uptake of activin A, whereas chloroquine suppressed lysosomal
      degradation following internalization, as demonstrated by microscopic
      autoradiography. These results suggest that cell-associated FS-288 accelerates
      the uptake of activin A into pituitary cells, leading to increased degradation by
      lysosomal enzymes, and thus plays a role in the activin clearance system.

PMID- 9153242
TI  - cDNA cloning and expression of a novel UDP-N-acetyl-D-galactosamine:polypeptide N
      acetylgalactosaminyltransferase.
AB  - The cDNA for a fourth member of the mammalian UDP-GalNAc:polypeptide N
      acetylgalactosaminyltransferase family, termed ppGaNTase-T4, has been cloned from
      a murine spleen cDNA library and expressed transiently in COS7 cells as a
      secreted functional enzyme. Degenerate primers, based upon regions that are
      conserved among the known mammalian members of the enzyme family (ppGaNTase-T1, 
      T2, and -T3) and three Caenorhabditis elegans homologues (ppGaNTase-TA, -TB, and 
      TC), were used in polymerase chain reactions to identify and clone this new
      isoform. Substrate preferences for recombinant murine ppGaNTase-T1 and ppGaNTase
      T4 isozymes were readily distinguished. ppGaNTase-T1 glycosylated a broader range
      of synthetic peptide substrates; in contrast, the ppGaNTase-T4 preferentially
      glycosylated a single substrate among the panel of 11 peptides tested. Using
      Northern blot analysis, a ppGaNTase-T4 message of 5.5 kilobases was detectable in
      murine embryonic tissues, as well as the adult sublingual gland, stomach, colon,
      small intestine, lung, cervix, and uterus with lower levels detected in kidney,
      liver, heart, brain, spleen, and ovary. Thus, the pattern of expression for
      ppGaNTase-T4 is more restricted than for the three previously reported isoforms
      of the enzyme. The variation in expression patterns and substrate specificities
      of the ppGaNTase enzyme family suggests that differential expression of these
      isoenzymes may be responsible for the cell-specific repertoire of mucin-type
      oligosaccharides on cell-surface and secreted O-linked glycoproteins.

PMID- 9153243
TI  - The thiol-dependent reductase ERp57 interacts specifically with N-glycosylated
      integral membrane proteins.
AB  - The lumen of the endoplasmic reticulum contains a number of distinct molecular
      chaperones and folding factors, which modulate the folding and assembly of newly
      synthesized proteins and protein complexes. A subset of these luminal components
      are specific for glycoproteins, and, like calnexin and calreticulin, the thiol
      dependent reductase ERp57 has been shown to interact specifically with soluble
      secretory proteins bearing N-linked carbohydrate. Calnexin and calreticulin also
      interact with glycosylated integral membrane proteins, and in this study we have
      examined the interaction of ERp57 with these substrates. As with soluble
      proteins, the binding of ERp57 to an integral membrane protein is dependent upon
      the protein bearing an N-glycan that has undergone glucose trimming. Furthermore,
      ERp57 binds to newly synthesized glycoproteins in combination with either
      calnexin or calreticulin. We propose that ERp57 acts in concert with calnexin and
      calreticulin to modulate glycoprotein folding and enforce the glycoprotein
      specific quality control mechanism operating in the endoplasmic reticulum.

PMID- 9153244
TI  - Differential inhibition and posttranslational modification of protein phosphatase
      1 and 2A in MCF7 cells treated with calyculin-A, okadaic acid, and tautomycin.
AB  - Calyculin-A (CA), okadaic acid (OA), and tautomycin (TAU) are potent inhibitors
      of protein phosphatases 1 (PP1) and 2A (PP2A) and are widely used on cells in
      culture. Despite their well characterized selectivity in vitro, their exact
      intracellular effects on PP1 and PP2A cannot be directly deduced from their
      extracellular concentration because their cell permeation properties are not
      known. Here we demonstrate that, due to the tight binding of the inhibitors to
      PP1 and/or PP2A, their cell penetration could be monitored by measuring PP1 and
      PP2A activities in cell-free extracts. Treatment of MCF7 cells with 10 nM CA for
      2 h simultaneously inhibited PP1 and PP2A activities by more than 50%. A
      concentration of 1 microM OA was required to obtain a similar time course of PP2A
      inhibition in MCF7 cells to that observed with 10 nM CA, whereas PP1 activity was
      unaffected. PP1 was predominantly inhibited in MCF7 cells treated with TAU but
      even at 10 microM TAU PP1 inhibition was much slower than that observed with 10
      nM CA. Furthermore, binding of inhibitors to PP2Ac and/or PP1c in MCF7 cells led
      to differential posttranslational modifications of the carboxyl termini of the
      proteins as demonstrated by Western blotting. OA and CA, in contrast to TAU,
      induced demethylation of the carboxyl-terminal Leu309 residue of PP2Ac. On the
      other hand, CA and TAU, in contrast to OA, elicited a marked decrease in
      immunoreactivity of the carboxyl terminus of the alpha-isoform of PP1c, probably
      reflecting proteolysis of the protein. These results suggest that in MCF7 cells
      OA selectively inhibits PP2A and TAU predominantly affects PP1, a conclusion
      supported by their differential effects on cytokeratins in this cell line.

PMID- 9153245
TI  - Regulation of type I collagen mRNA by amino acid deprivation in human lung
      fibroblasts.
AB  - The steady state levels of alpha1(I) collagen mRNA are decreased by retinoic acid
      and prostaglandin E2. These effector substances decrease the uptake of A system
      amino acids. We examined the effect of amino acid deprivation on the steady state
      levels of alpha1(I) collagen in human lung fibroblasts. Maintenance of
      fibroblasts in amino acid-free medium decreased alpha1(I) collagen mRNA levels by
      29% at 24 h and 78% at 72 h. Frequent refeeding of cultures with amino acid-free
      medium resulted in more rapid decreases in intracellular amino acids and in
      alpha1(I) collagen mRNA levels. The decrease in alpha1(I) collagen mRNA levels
      was mediated by decreases in mRNA stability as assessed by a half-life
      determination using actinomycin D and by decreases in the rate of transcription
      as assessed by nuclear run-on assay. Treatment of fibroblasts with medium
      containing amino acids resulted in rapid restoration of alpha1(I) collagen mRNA
      levels. This increase in alpha1(I) collagen mRNA expression required protein
      synthesis as determined by cycloheximide sensitivity and was inhibited by
      prostaglandin E2. These data indicate that alpha1(I) collagen mRNA levels are
      sensitive to alterations in the amount of intracellular amino acids and suggest a
      potential mechanism whereby alpha1(I) collagen accumulation may be regulated
      independent of inflammatory mediators following lung injury.

PMID- 9153246
TI  - Agonist-induced desensitization, internalization, and phosphorylation of the
      sst2A somatostatin receptor.
AB  - Cellular responsiveness to the inhibitory peptide somatostatin (SRIF) or its
      clinically used analogs can desensitize with agonist exposure. While
      desensitization of other seven-transmembrane domain receptors is mediated by
      receptor phosphorylation and/or internalization, the mechanisms mediating SRIF
      receptor (sst) desensitization are unknown. Therefore, we investigated the
      susceptibility of the sst2A receptor isotype to ligand-induced desensitization,
      internalization, and phosphorylation in GH-R2 cells, a clone of pituitary tumor
      cells overexpressing this receptor. A 30-min exposure of cells to either SRIF or
      the analog SMS 201-995 (SMS) reduced both the potency and efficacy of agonist
      inhibition of adenylyl cyclase. Internalization of receptor-bound ligand was
      rapid (t1/2 = 4 min) and temperature-dependent. SRIF and SMS increased the
      phosphorylation of the 71-kDa sst2A protein 25-fold within 15 min. Receptor
      phosphorylation was dependent on both the concentration and time of agonist
      exposure and was not affected by pertussis toxin pretreatment, indicating that
      receptor occupancy rather than second messenger formation was required. Receptor
      phosphorylation was also stimulated by phorbol 12-myristate 13-acetate activation
      of protein kinase C. Both ligand-stimulated and phorbol 12-myristate 13-acetate
      stimulated receptor phosphorylation occurred primarily on serine. These studies
      are the first demonstration of agonist-dependent desensitization,
      internalization, and phosphorylation of the sst2A receptor and suggest that
      phosphorylation may mediate the homologous and heterologous regulation of this
      receptor.

PMID- 9153247
TI  - Beta subunit heterogeneity in neuronal L-type Ca2+ channels.
AB  - Heterologous expression studies have shown that the activity of voltage-gated
      Ca2+ channels is regulated by their beta subunits in a beta subunit isoform
      specific manner. In this study we therefore investigated if one or several beta
      subunit isoforms associate with L-type Ca2+ channels in different regions of
      mammalian brain. All four beta subunit isoforms (beta1b, beta2, beta3, and beta4)
      are expressed in cerebral cortex as shown in immunoblots. Immunoprecipitation of
      (+)-[3H]isradipine-labeled L-type channels revealed that the majority of beta
      subunit-associated L-type channels was associated with beta3 (42 +/- 8%) and
      beta4 (42 +/- 7%) subunits, whereas beta1b and beta2 were present in a smaller
      fraction of channel complexes. beta3 and beta4 were also the major L-type channel
      beta subunits in hippocampus. In cerebellum beta1b, beta2, and beta3 but not
      beta4 subunits were expressed at lower levels than in cortex. Accordingly, beta4
      was the most prominent beta subunit in cerebellar L-type channels. This beta
      subunit composition was very similar to the one determined for 125I-omega
      conotoxin-GVIA-labeled N-type and 125I-omega-conotoxin-MVIIC-labeled P/Q-type
      channel complexes in cerebral cortex and cerebellum. Our data show that all four
      beta subunit isoforms associate with L-type Ca2+ channels in mammalian brain.
      This beta subunit heterogeneity may play an important role for the fine tuning of
      L-type channel function and modulation in neurons.

PMID- 9153248
TI  - The roles of pteridine reductase 1 and dihydrofolate reductase-thymidylate
      synthase in pteridine metabolism in the protozoan parasite Leishmania major.
AB  - Trypanosomatid protozoans depend upon exogenous sources of pteridines (pterins or
      folates) for growth. A broad spectrum pteridine reductase (PTR1) was recently
      identified in Leishmania major, whose sequence places it in the short chain
      alcohol dehydrogenase protein family although its enzymatic activities resemble
      dihydrofolate reductases. The properties of PTR1 suggested a role in essential
      pteridine salvage as well as in antifolate resistance. To prove this, we have
      characterized further the properties and relative roles of PTR1 and dihydrofolate
      reductase-thymidylate synthase in Leishmania pteridine metabolism, using purified
      enzymes and knockout mutants. Recombinant L. major and Leishmania tarentolae, and
      native L. major PTR1s, were tetramers of 30-kDa subunits and showed similar
      catalytic properties with pterins and folates (pH dependence, substrate
      inhibition with H2pteridines). Unlike PTR1, dihydrofolate reductase-thymidylate
      synthase showed weak activity with folate and no activity with pterins.
      Correspondingly, studies of ptr1(-) and dhfr-ts- mutants implicated only PTR1 in
      the ability of L. major to grow on a wide array of pterins. PTR1 exhibited 2000
      fold less sensitivity to inhibition by methotrexate than dihydrofolate reductase
      thymidylate synthase, suggesting several mechanisms by which PTR1 may compromise
      antifolate inhibition in wild-type Leishmania and lines bearing PTR1
      amplifications. We incorporate these results into a comprehensive model of
      pteridine metabolism and discuss its implications in chemotherapy of this
      important human pathogen.

PMID- 9153249
TI  - Utilization of recombinant adenovirus and dominant negative mutants to
      characterize hepatocyte nuclear factor 4-regulated apolipoprotein AI and CIII
      expression.
AB  - Using recombinant adenoviral vectors and a dominant negative mutant of HNF-4, we
      have examined the contribution of hepatocyte nuclear factor 4 (HNF-4) to
      endogenous apolipoprotein AI and CIII mRNA expression. Overexpression of HNF-4
      leads to a 7.4-fold increase in apolipoprotein CIII expression, while infection
      with the dominant negative mutant of HNF-4 reduces the level of apolipoprotein
      CIII mRNA by 80%, demonstrating that endogenous HNF-4 is necessary for
      apolipoprotein CIII expression. Experiments using the hepatoma cell lines, HepG2
      and Hep3B, indicate that HNF-4 is also involved in the regulation of
      apolipoprotein AI expression in these lines. However, the effect of HNF-4 on
      apolipoprotein AI expression is much more dramatic in cell lines derived from
      intestinal epithelium. Infection of the intestinal-derived cell line IEC-6 with
      the HNF-4 adenovirus resulted in a greater than 20-fold increase in the level of
      apolipoprotein AI mRNA. These results indicate that HNF-4 does regulate
      apolipoprotein AI and CIII mRNA expression and suggest that HNF-4 is critical for
      intestinal apolipoprotein AI expression.

PMID- 9153250
TI  - Equistatin, a new inhibitor of cysteine proteinases from Actinia equina, is
      structurally related to thyroglobulin type-1 domain.
AB  - It is well known that the activities of the lysosomal cysteine proteinases are
      tightly regulated by their endogenous inhibitors, cystatins. Here we report a new
      inhibitor of cysteine proteinases isolated from sea anemone Actinia equina. The
      inhibitor, equistatin, is an acidic protein with pI 4.7 and molecular weight of
      14,129. It binds tightly and rapidly to cathepsin L (ka = 5.7 x 10(7) M-1 s-1, Ki
      = 0.051 nM) and papain (ka = 1.2 x 10(7) M-1 s-1, Ki = 0.57 nM). The lower
      affinity for cathepsin B (Ki = 1.4 nM) was shown to be due mainly to a lower
      second order association rate constant (ka = 0.04 x 10(6) M-1 s-1). The inhibitor
      is composed of 128 amino acids forming two repeated domains with 48% identity.
      Neither of the domains shows any sequence homology to cystatins, but they do show
      a significant homology to thyroglobulin type-1 domains. A highly conserved
      consensus sequence motif of Cys-Trp-Cys-Val together with conserved Cys, Pro, and
      Gly residues is present in major histocompatibility complex class II-associated
      p41 invariant chain, nidogen, insulin-like growth factor proteins, saxiphilin
      domain a, pancreatic carcinoma marker proteins (GA733), and chum salmon egg
      cysteine proteinase inhibitor. In each of the domains of the equistatin, the
      three residues are similarly conserved, and the sequences Val-Trp-Cys-Val and Cys
      Trp-Cys-Val are present in domains a and b, respectively. We suggest that
      equistatin belongs to a new superfamily of protein inhibitors of cysteine
      proteinases named thyroglobulin type-1 domain inhibitors. This superfamily
      currently includes equistatin, major histocompatibility complex class II-
      associated p41 invariant chain fragment, and chum salmon egg cysteine proteinase
      inhibitor.

PMID- 9153252
TI  - Down-regulation of the filamentous actin cross-linking activity of cortactin by
      Src-mediated tyrosine phosphorylation.
AB  - Cortactin, a prominent substrate for pp60(c-src), is a filamentous actin (F
      actin) binding protein. We show here that cortactin can promote sedimentation of
      F-actin at centrifugation forces under which F-actin is otherwise not able to be
      precipitated. Electron microscopic analysis after negative staining further
      revealed that actin filaments in the presence of cortactin are cross-linked into
      bundles of various degrees of thickness. Hence, cortactin is also an F-actin
      cross-linking protein. We also demonstrate that the optimal F-actin cross-linking
      activity of cortactin requires a physiological pH in a range of 7.3-7.5.
      Furthermore, pp60(c-src) phosphorylates cortactin in vitro, resulting in a
      dramatic reduction of its F-actin cross-linking activity in a manner depending on
      levels of tyrosine phosphorylation. In addition, pp60(c-src) moderately inhibits
      the F-actin binding activity of cortactin. This study presents the first evidence
      that pp60(c-src) can directly regulate the activity of its substrate toward the
      cytoskeleton and implies a role of cortactin as an F-actin modulator in tyrosine
      kinase-regulated cytoskeleton reorganization.

PMID- 9153251
TI  - A role of dystroglycan in schwannoma cell adhesion to laminin.
AB  - Dystroglycan is encoded by a single gene and cleaved into two proteins alpha- and
      beta-dystroglycan by posttranslational processing. Recently, alpha-dystroglycan
      was demonstrated to be an extracellular laminin-binding protein anchored to the
      cell membrane by a transmembrane protein beta-dystroglycan in striated muscle and
      Schwann cells. However, the biological functions of the dystroglycan-laminin
      interaction remain obscure, and in particular, it is still unclear if
      dystroglycan plays a role in cell adhesion. In the present study, we
      characterized the role of dystroglycan in the adhesion of schwannoma cells to
      laminin-1. Immunochemical analysis demonstrated that the dystroglycan complex,
      comprised of alpha- and beta-dystroglycan, was a major laminin-binding protein
      complex in the surface membrane of rat schwannoma cell line RT4. It also
      demonstrated the presence of alpha-dystroglycan, but not beta-dystroglycan, in
      the culture medium, suggesting secretion of alpha-dystroglycan by RT4 cells. RT4
      cells cultured on dishes coated with laminin-1 became spindle in shape and
      adhered to the bottom surface tightly. Monoclonal antibody IIH6 against alpha
      dystroglycan was shown previously to inhibit the binding of laminin-1 to alpha
      dystroglycan. In the presence of IIH6, but not several other control antibodies
      in the culture medium, RT4 cells remained round in shape and did not adhere to
      the bottom surface. The adhesion of RT4 cells to dishes coated with fibronectin
      was not affected by IIH6. The known inhibitors of the interaction of alpha
      dystroglycan with laminin-1, including EDTA, sulfatide, fucoidan, dextran
      sulfate, heparin, and sialic acid, also perturbed the adhesion of RT4 cells to
      laminin-1, whereas the reagents which do not inhibit the interaction, including
      dextran, chondroitin sulfate, dermatan sulfate, and GlcNAc, did not. Altogether,
      these results support a role for dystroglycan as a major cell adhesion molecule
      in the surface membrane of RT4 cells.

PMID- 9153253
TI  - Translesional synthesis on DNA templates containing a single abasic site. A
      mechanistic study of the "A rule".
AB  - Site-specifically modified oligodeoxynucleotides containing a single natural
      abasic site or a chemically synthesized (tetrahydrofuran or deoxyribitol) model
      abasic site were used as templates for primer extension reactions catalyzed by
      the Klenow fragment of Escherichia coli DNA polymerase I or by calf thymus DNA
      polymerase alpha. Analysis of the fully extended products of these reactions
      indicated that both polymerases preferentially incorporate dAMP opposite the
      natural abasic site and tetrahydrofuran, while DNA templates containing the ring
      opened deoxyribitol moiety block translesional synthesis, promoting sequence
      context-dependent deletions. The frequency of nucleotide insertion opposite the
      three types of abasic sites follows the order dAMP > dGMP > dCMP > dTMP. The
      frequency of chain extension was highest when dAMP was positioned opposite a
      natural abasic site. The frequency of translesional synthesis past abasic sites
      follows the order tetrahydrofuran > deoxyribose > deoxyribitol. The Klenow
      fragment promotes blunt end addition of dAMP; this reaction was much less
      efficient than insertion of dAMP opposite an abasic site. We conclude that the
      miscoding potential of a natural abasic site in vitro closely resembles that of
      its tetrahydrofuran analog. Ring-opened abasic sites favor deletions. Studies
      with polymerase alpha in vitro predict preferential incorporation of dAMP at
      abasic sites in mammalian cells.

PMID- 9153254
TI  - Site-directed mutagenesis of human leukotriene C4 synthase.
AB  - The functional characteristics of leukotriene C4 synthase (LTC4S), which
      specifically conjugates leukotriene A4 with GSH, were assessed by mutagenic
      analysis. Human LTC4S and the 5-lipoxygenase-activating protein share substantial
      amino acid identity and predicted secondary structure. The mutation of Arg-51 of
      LTC4S to Thr or Ile abolishes the enzyme function, whereas the mutation of Arg-51
      to His or Lys provides a fully active recombinant protein. The mutations Y59F,
      Y97F, Y93F, N55A, V49F, and A52S increase the Km of the recombinant microsomal
      enzyme for GSH. The mutation Y93F also markedly reduces enzyme function and
      increases the optimum for pH-dependent activity. The deletion of the third
      hydrophobic domain with the carboxyl terminus abolishes the enzyme activity, and
      function is restored by the substitution of the third hydrophobic domain and
      carboxyl terminus of 5-lipoxygenase-activating protein for that of LTC4S.
      Mutations of C56S and C82V alone or together and the deletion of Lys-2 and Asp-3
      of LTC4S do not alter enzyme function. The direct linkage of two LTC4S monomers
      by a 12-amino acid bridge provides an active dimer, and the same bridging of
      inactive R51I with a wild-type monomer creates an active pseudo-dimer with
      function similar to that of the wild-type enzyme. These results suggest that in
      the catalytic function of LTC4S, Arg-51 probably opens the epoxide ring and Tyr
      93 provides the thiolate anion of GSH. Furthermore, the monomer has independent
      conjugation activity, and dimerization of LTC4S maintains the proper protein
      structure.

PMID- 9153255
TI  - Bafilomycin A1 treatment retards transferrin receptor recycling more than bulk
      membrane recycling.
AB  - Treatment of Chinese hamster ovary cells with the vacuolar proton pump inhibitor
      bafilomycin A1 causes a 2-fold retardation in the rate of recycling of
      transfected human transferrin receptors back to the cell surface as measured
      using biochemical assays (Johnson, L. S. , Dunn, K. W., Pytowski, B., and McGraw,
      T. E. (1993) Mol. Biol. Cell 4, 1251-1266). We have used quantitative
      fluorescence microscopy to determine which step(s) in the endocytic recycling
      pathway are affected. We show that removal of transferrin from sorting endosomes
      and accumulation in the peri-centriolar endocytic recycling compartment takes
      place normally in bafilomycin A1-treated cells. However, the rate constant for
      exit of transferrin receptors from recycling endosomes (ke) is reduced from 0.063
      min-1 in untreated cells to 0.034 min-1 in the presence of bafilomycin A1. This
      retardation appears to be dependent on the presence of internalization motifs in
      the cytoplasmic domain since modified receptors lacking these oligopeptide motifs
      do not show as large a decrease in recycling rate in the presence of bafilomycin
      A1. Bulk membrane recycling (measured by efflux of an internalized fluorescent
      lipid analog, 6-[N-[7-nitrobenzo-2-oxa-1, 3-diazol-4-yl--amino-hexoyl-
      sphingosylphosphorylcholine) is slowed from an exit rate constant of 0.060 min-1
      without drug to 0.046 min-1 in the presence of bafilomycin A1. We conclude that
      bafilomycin A1 slows bulk membrane flow, but it causes additional inhibition of
      receptor recycling in a manner that is dependent on a peptide motif on the
      cytoplasmic domain.

PMID- 9153256
TI  - Overexpression of the integrin-linked kinase promotes anchorage-independent cell
      cycle progression.
AB  - Cell adhesion to substratum has been shown to regulate cyclin A expression as
      well as cyclin D- and E-dependent kinases, the latter via the up-regulation of
      cyclin D1 and the down-regulation of cyclin-Cdk inhibitors p21 and p27,
      respectively. This adhesion-dependent regulation of cell cycle is thought to be
      mediated by integrins. Here we demonstrate that stable transfection and
      overexpression of the integrin-linked kinase (ILK), which interacts with the
      beta1 and beta3 integrin cytoplasmic domains, induces anchorage-independent cell
      cycle progression but not serum-independent growth of rat intestinal epithelial
      cells (IEC18). ILK overexpression results in increased expression of cyclin D1,
      activation of Cdk4 and cyclin E-associated kinases, and hyperphosphorylation of
      the retinoblastoma protein. In addition, ILK overexpression results in the
      expression of p21 and p27 Cdk inhibitors with altered electrophoretic mobilities,
      with the p27 from ILK-overexpressing cells having reduced inhibitory activity.
      The transfer of serum-exposed IEC18 cells from adherent cultures to suspension
      cultures results in a rapid down-regulation of expression of cyclin D1 and cyclin
      A proteins as well as in retinoblastoma protein dephosphorylation. In marked
      contrast, transfer of ILK-overexpressing cells from adherent to suspension
      cultures results in continued high levels of expression of cyclin D1 and cyclin A
      proteins, and a substantial proportion of the retinoblastoma protein remains in a
      hyperphosphorylated state. These results indicate that, when overexpressed, ILK
      induces signaling pathways resulting in the stimulation of G1/S cyclin-Cdk
      activities, which are normally regulated by cell adhesion and integrin
      engagement.

PMID- 9153257
TI  - Replication fork bypass of a pyrimidine dimer blocking leading strand DNA
      synthesis.
AB  - We constructed a double-stranded plasmid containing a single cis, syn-cyclobutane
      thymine dimer (T[c,s]T) 385 base pairs from the center of the SV40 origin of
      replication. This circular DNA was replicated in vitro by extracts from several
      types of human cells. The dimer was placed on the leading strand template of the
      first replication fork to encounter the lesion. Two-dimensional gel
      electrophoresis of replication intermediates documented the transient arrest of
      the replication fork by the dimer. Movement of the replication fork beyond the
      dimer was recognized by the appearance of a single fork arc in DNA sequences
      located between the T[c,s]T and the half-way point around the circular template
      (180 degrees from the origin). Upon completion of plasmid replication, the
      T[c,s]T was detected by T4 endonuclease V in about one-half (46 +/- 9%) of the
      closed circular daughter molecules. Our results demonstrate that extracts
      prepared from HeLa cells and SV40-transformed human fibroblasts (SV80, IDH4),
      including a cell line defective in nucleotide-excision repair (XPA), were
      competent for leading strand DNA synthesis opposite the pyrimidine dimer and
      replication fork bypass. In contrast, dimer bypass was severely impaired in
      otherwise replication-competent extracts from two different xeroderma pigmentosum
      variant cell lines.

PMID- 9153258
TI  - Autocatalytic activation of human cathepsin K.
AB  - The in vitro activation of the recombinant purified human cathepsin K (EC
      3.4.22.38) was examined by mutagenesis. Cathepsin K was expressed as a secreted
      proenzyme using baculovirus-infected Sf21 insect cells. Spontaneous in vitro
      activation of procathepsin K occurred at pH 4 and was catalyzed by exogenous
      mature cathepsin K. Three intermediates were identified as resulting from
      cleavages after Glu19, Ser98, and Glu110. The mature enzyme was composed of
      mixture of enzymes with N termini of Gly113, Arg114, and Ala115 with varying
      ratios depending on the preparation. Molecular weight determinations were
      consistent with the absence of carbohydrate in the mature protein, while
      electrospray mass spectroscopy indicated that six of the eight cysteine residues
      were in disulfide linkage, and that the protein had Met329 as the C-terminal
      residue. A mutant was constructed in which the active site Cys139 was changed to
      Ser. [Ser139,Ala163]Procathepsin K (containing mutation C139S,S163A) failed to
      spontaneously process and was only partially processed in the presence of 1%
      exogenous wild-type mature cathepsin K forming intermediates, which were
      identical to those observed in the activation of wild-type.
      [Ser139,Ala163]Procathepsin K could be fully processed to mature enzyme by
      including one equivalent of wild-type procathepsin K in the activation mixture.
      These results indicated that in vitro activation of the procathepsin K was an
      autocatalytic process.

PMID- 9153259
TI  - Chemoattractant receptor-induced phosphorylation of L-selectin.
AB  - The selectin adhesion molecules and chemoattractant receptors synergistically
      regulate leukocyte migration into lymphoid tissues and sites of inflammation, but
      little is known about how these families of receptors modulate each other's
      function. In this study, L-selectin was found to be phosphorylated in
      lymphoblastoid cell lines, and phosphorylation was enhanced by phorbol ester
      (phorbol 12-myristate 13-acetate (PMA)) treatment. Interactions between L
      selectin and chemoattractant receptors were therefore examined using transfected
      rat basophilic leukemia cell lines (RBL-2H3) that expressed human L-selectin
      along with human leukocyte chemoattractant receptors. L-selectin was rapidly
      phosphorylated in cells treated with chemoattractants, thrombin, IgE receptor
      agonists, or PMA. Pertussis toxin or the protein kinase C inhibitor,
      staurosporine, completely blocked chemoattractant receptor-induced
      phosphorylation of L-selectin. PMA-induced phosphorylation was on serine residues
      within the cytoplasmic tail of L-selectin that have been well conserved during
      recent evolution. Although L-selectin phosphorylation was not essential for basal
      levels of adhesion through L-selectin in transformed cell lines, the rapid
      increase in ligand binding activity of L-selectin that occurs following leukocyte
      activation was blocked by staurosporine. These results demonstrate that L
      selectin can be phosphorylated following engagement of chemoattractant receptors
      and suggest that this may be a physiologically relevant mechanism for the
      synergistic regulation of these receptors during leukocyte migration.

PMID- 9153260
TI  - Identification of the phosphorylated sites of metabolically 32P-labeled
      osteopontin from cultured chicken osteoblasts.
AB  - Osteopontin (OPN) is one of the major secretory phosphoproteins in both
      calcifying and non-calcifying tissues. Evidence has accumulated for the
      biological importance of the phosphoproteins and, in particular, the phosphate
      groups in bone formation, resorption, and calcification. The precise locations of
      the phosphate groups in the OPN molecule were determined by metabolically
      labeling OPN with 32P in cultured chicken osteoblasts, followed by purification
      to homogeneity. N-terminal sequencing showed a single sequence of WPVSKRQHAISA,
      consistent with that deduced from both cDNA, and previous amino acid sequencing
      of the protein isolated from chicken bone. Three 32P-labeled peptides were
      isolated by reverse-phase high performance liquid chromatography of thrombin
      digested, 32P-labeled OPN. The N-terminal sequencing of each of these thrombin
      fragments gave single sequences as follows: WPVSKSRQHAIS, SHHTHRYHQDHVD, and
      ASKLRKAARKL, with approximate molecular masses of 5, 30, and 20 kDa. These data
      demonstrate that 32P was incorporated throughout the N- to C-terminal sequence of
      the protein. Thrombin specifically cleaved chicken OPN at two sites: between Arg
      22 and Ser-23, which generated the 5-kDa N-terminal end fragment, and another
      between Lys-138 and Ala-139, which generated the 30- and 20-kDa fragments. To
      further define the exact locations of the phosphorylated amino acids and the
      surrounding amino acid sequences, OPN was digested with trypsin, which generated
      seven major 32P-labeled peptides whose amino acid sequences were determined. The
      phosphorylated peptide regions of osteopontin were identified as amino acids 8-18
      (QHAIS*AS*S*EEK), 39-54 (LASQQTHYS*S*EENAD), 150-171 (LIEDDAT*AEVGDSQLAGLWLPK),
      179-191 (ELAQHQSVENDSR), 194-205 (FDS*PEVGGDSK), 214-219 (ES*LASR), and 239-248
      (HSIENNEVTR). The phosphorylated amino acid sites are followed by an asterisk
      (*). Of the seven identified phosphorylated peptide regions, three were localized
      on the N-terminal end of the osteopontin molecule (with five phosphorylated
      serines) and contained the sequence motifs that were phosphorylated by casein
      kinase II type(s), whereas the remaining four peptides are concentrated toward
      the C-terminal half of the molecule (with five phosphorylated residues) and
      contained recognition motifs for other kinases as well as casein kinase II.

PMID- 9153261
TI  - A human-specific polymorphism in the coding region of the aggrecan gene. Variable
      number of tandem repeats produce a range of core protein sizes in the general
      population.
AB  - Aggrecan, one of the major structural genes of cartilage, encodes a proteoglycan
      core protein composed of an extended central glycosaminoglycan-bearing domain,
      flanked by globular domains at each end. The central region consists of long
      stretches of repeating amino acids that serve as attachment sites for
      glycosaminoglycans such as chondroitin and keratan sulfate; the terminal globular
      domains interact with other cartilage components. The glycosaminoglycan
      attachment region is encoded in several species by a single large exon, within
      which are several different types of repeating sequences. Several species show
      within this exon a similar block of conserved repeats for attachment of
      chondroitin sulfate, but in humans this group of repeats is particularly well
      conserved. Examination of genomic DNA from a population of unrelated individuals
      by polymerase chain reaction or Southern blot assays shows this block of repeat
      sequences exists in multiple allelic forms, which differ by the number of repeats
      at this site in each allele. Thirteen different alleles have been identified,
      with repeat numbers ranging from 13 to 33. This is an unusual example of an
      expressed variable number of tandem repeat polymorphism. This polymorphism is
      apparently restricted to humans, of several species examined. This polymorphism
      results in individuals with differing length aggrecan core proteins, bearing
      different numbers of potential attachment sites for chondroitin sulfate. The
      possibility exists for a molecular understanding of biological variation in
      cartilage functional properties.

PMID- 9153262
TI  - Molecular cloning and expression of Chinese hamster ovary cell heparan-sulfate 2
      sulfotransferase.
AB  - Heparan-sulfate 2-sulfotransferase (HS2ST), which catalyzes the transfer of
      sulfate from 3'-phosphoadenosine 5'-phosphosulfate to L-iduronic acid at position
      2 in heparan sulfate, was purified from cultured Chinese hamster ovary (CHO)
      cells to apparent homogeneity (Kobayashi, M., Habuchi, H., Habuchi, O., Saito,
      M., and Kimata, K. (1996) J. Biol. Chem. 271, 7645-7653). The internal amino acid
      sequences were obtained from the peptides after digestion of the purified protein
      with a combination of endoproteinases. Mixed oligonucleotides based on the
      peptide sequences were used as primers to obtain a probe fragment by reverse
      transcriptase-polymerase chain reaction using CHO cell poly(A)+ RNA as template.
      The clone obtained from a CHO cDNA library by screening with the probe is 2.2
      kilobases in size and contains an open reading frame of 1068 bases encoding a new
      protein composed of 356 amino acid residues. The protein predicts a type II
      transmembrane topology similar to other Golgi membrane proteins. Messages of 5.0
      and 3.0 kilobases were observed in Northern analysis. Evidence that the cDNA
      clone corresponds to the purified HS2ST protein is as follows. (a) The predicted
      amino acid sequence contains all five peptides obtained after endoproteinase
      digestion of the purified protein; (b) the characteristics of the predicted
      protein fit those of the purified protein in terms of molecular mass, membrane
      localization, and N-glycosylation; and (c) when the cDNA containing the entire
      coding sequence of the enzyme in a eukaryotic expression vector was transfected
      into COS-7 cells, the HS2ST activity increased 2.6-fold over controls, and the
      FLAG-HS2ST fusion protein purified by affinity chromatography showed the HS2ST
      activity alone.

PMID- 9153263
TI  - Reverse gyrase from Methanopyrus kandleri. Reconstitution of an active
      extremozyme from its two recombinant subunits.
AB  - Reverse gyrases are ATP-dependent type I 5'-topoisomerases that positively
      supercoil DNA. Reverse gyrase from Methanopyrus kandleri is unique as the first
      heterodimeric type I 5'-topoisomerase described, consisting of a 138-kDa subunit
      involved in the hydrolysis of ATP (RgyB) and a 43-kDa subunit that forms the
      covalent complex with DNA during the topoisomerase reaction (RgyA). Here we
      report the reconstitution of active reverse gyrase from the two recombinant
      proteins overexpressed in Escherichia coli. Both proteins have been purified by
      column chromatography to >90% homogeneity. RgyB has a DNA-dependent ATPase
      activity at high temperature (80 degrees C) and is independent of the presence of
      RgyA. RgyA alone has no detectable activity. The addition of RgyA to RgyB
      reconstitutes positive supercoiling activity, but the RgyB and RgyA subunits form
      a stable heterodimer only after being heated together. This is the first case in
      which it has been possible to reconstitute an active heterodimeric enzyme of a
      hyperthermophilic prokaryote from recombinant proteins.

PMID- 9153264
TI  - The negative signaling molecule SH2 domain-containing inositol-polyphosphate 5
      phosphatase (SHIP) binds to the tyrosine-phosphorylated beta subunit of the high
      affinity IgE receptor.
AB  - The SH2 domain-containing inositol-polyphosphate 5-phosphatase, SHIP, associates
      with FcgammaRIIB and negatively regulates both B-cell and mast cell function. We
      report here that SHIP was tyrosine-phosphorylated after high affinity IgE
      receptor (FcepsilonRI) aggregation in rat basophilic leukemia RBL-2H3 cells. The
      tyrosine phosphorylation of SHIP was an early event after receptor aggregation
      and was present in cells deficient in the protein-tyrosine kinase Syk.
      Furthermore it was not secondary to the increase of intracellular calcium or the
      activation of protein kinase C. SHIP was precipitated by immobilized
      phosphorylated synthetic peptides based on the immunoreceptor tyrosine-based
      activation motif (ITAM) of the beta but not the gamma subunit of the high
      affinity IgE receptor. Tyrosine phosphorylation of SHIP and its association with
      the tyrosine-phosphorylated beta subunit of FcepsilonRI could play an important
      role in down-regulating receptor-mediated signal transduction in mast cells.
      Thus, whereas the activation molecule Syk associates with the gamma subunit ITAM,
      the beta subunit ITAM binds the negative signaling molecule SHIP. Therefore,
      unlike B cells where the antigen receptor and coreceptors such as FcgammaRIIB or
      CD22 each recruits molecules with opposite effects, the FcepsilonRI contains
      subunits which recruit molecules that activate and inhibit signal transduction.

PMID- 9153265
TI  - Grapefruits and drugs: when is statistically significant clinically significant?

PMID- 9153266
TI  - More inflammatory effects of protease receptors.

PMID- 9153267
TI  - Cigarettes and the wages of sn-2: oxidized species of PAF in smoking hamsters.

PMID- 9153268
TI  - Cell adhesion in vascular biology. New insights into integrin-ligand interaction.

PMID- 9153269
TI  - Host/pathogen interactions. Subversion of the mammalian cell cytoskeleton by
      invasive bacteria.

PMID- 9153270
TI  - Differential regulation of gap junctions by proinflammatory mediators in vitro.
AB  - The development of inflammation is an important component of host defense against
      infection. The cellular and molecular processes underlying inflammation are well
      studied, and it is known that cells of the blood vessel wall, such as endothelial
      cells and smooth muscle cells, play pivotal roles. Additionally, a wide variety
      of proinflammatory mediators have been defined, which coordinate the
      multicellular processes of inflammation. Knowledge of the potential role of blood
      vessel gap junctional intercellular communication (GJIC) in coordinating the
      inflammation process, however, is limited. In this study, we report that
      bacterial lipopolysaccharide (LPS), as well as the proinflammatory cytokines TNF
      alpha and IL-1beta, selectively inhibit human myoendothelial GJIC in vitro
      without affecting GJIC between the respective homologous cell populations. This
      finding may represent a physiologically relevant component of the inflammatory
      response to infection. The work also provides some of the first clear evidence
      suggesting that a single eukaryotic cell can differentially regulate its GJIC
      between homologous and heterologous cell types in a simultaneous manner.

PMID- 9153271
TI  - Identification of rat yolk sac target protein of teratogenic antibodies, gp280,
      as intrinsic factor-cobalamin receptor.
AB  - Previous studies in the rat have shown that antibodies to gp280, a protein > 200
      kD and closely associated with the early endocytic system can induce fetal
      malformations. Although gp280 is thought to act as a receptor, its ligand(s) is
      not known. In the current study, we report that purified gp280 from rat kidney,
      like the intrinsic factor-Cobalamin receptor (IFCR), binds to the intrinsic
      factor-cobalamin (IFCbl) complex with an association constant of 0.3 x 10(9) M-1
      and mediates its internalization. Furthermore, antibodies raised to purified
      gp280 and IFCR inhibited the binding of IF-[57Co]Cbl complex to intestinal,
      renal, and yolk sac apical membranes and revealed a single identically sized
      protein on immunoblotting of the renal membranes. Both antibodies precipitated a
      single radiolabeled protein > 200 kD from cellular extract from [35S]methionine
      labeled yolk sac epithelial cells, and antibody to gp280 inhibited the uptake and
      internalization of 125IF-Cbl. Immunoelectron microscopy using the two antibodies
      revealed that in the kidney, both proteins were colocalized. These observations
      suggest that IF-Cbl complex is a ligand for gp280 and that gp280 and IFCR are
      identical proteins.

PMID- 9153272
TI  - Thrombin-mediated activation of factor XI results in a thrombin-activatable
      fibrinolysis inhibitor-dependent inhibition of fibrinolysis.
AB  - Recently, it has been shown that Factor XI can be activated by thrombin, and that
      Factor XIa significantly contributes to the generation of thrombin via the
      intrinsic pathway after the clot has been formed. This additional thrombin,
      generated inside the clot, was found to protect the clot from fibrinolysis. A
      plausible mechanism for this inhibitory effect of thrombin involves TAFI
      (thrombin-activatable fibrinolysis inhibitor, procarboxypeptidase B) which, upon
      activation, may inhibit fibrinolysis by removing carboxy-terminal lysines from
      fibrin. We studied the role of Factor XI and TAFI in fibrinolysis using a clot
      lysis assay. The lysis time was decreased twofold when TAFI was absent, when TAFI
      activation was inhibited by anti-TAFI antibodies, or when activated TAFI was
      inhibited by the competitive inhibitor (2-guanidinoethylmercapto)succinic acid.
      Inhibition of either TAFI activation or Factor XIa exhibited equivalent
      profibrinolytic effects. In the absence of TAFI, no additional effect of anti
      Factor XI was observed on the rate of clot lysis. We conclude that the mechanism
      of Factor XI-dependent inhibition of fibrinolysis is through the generation of
      thrombin via the intrinsic pathway, and is dependent upon TAFI. This pathway may
      play a role in determining the fate of in vivo formed clots.

PMID- 9153273
TI  - Expression of the calcium-sensing receptor on human antral gastrin cells in
      culture.
AB  - The presence of the extracellular calcium-sensing receptor on human antral
      gastrin cells was investigated. Reverse transcription PCR using mRNA isolated
      from gastrin cell- enriched cell cultures identified a product with a sequence
      identical to part of the human parathyroid-secreting cell calcium-sensing
      receptor. Immunocytochemistry with an antibody to the extracellular region of the
      receptor immunostained all gastrin cells (but not mucin or somatostatin cells),
      and detected appropriate-sized bands in Western blots of whole cell lysates.
      Increasing extracellular calcium levels from 0.5 to 9 mM stimulated gastrin
      release in a concentration-dependent manner, with maximal release obtained at 7.2
      mM. A known agonist of the calcium receptor, spermine also stimulated gastrin
      release. Microfluorimetry of identified gastrin cells demonstrated that
      increasing extracellular calcium resulted in an initial rapid rise in
      intracellular calcium followed by a plateau level that returned to basal levels
      immediately after removal of the elevated calcium. The traces were consistent
      with activation of a receptor-mediated mechanism rather than a concentration
      dependent influx of calcium. In conclusion, these data indicate that G cells
      express the calcium-sensing receptor, and that activation of the receptor may
      explain the acid rebound phenomenon associated with calcium-containing antacid
      preparations.

PMID- 9153275
TI  - Detection of ebaf, a novel human gene of the transforming growth factor beta
      superfamily association of gene expression with endometrial bleeding.
AB  - Human endometrium is unique since it is the only tissue in the body that bleeds
      at regular intervals. In addition, abnormal endometrial bleeding is one of the
      most common manifestations of gynecological diseases, and is a prime indication
      for hysterectomy. Here, we report on a novel human gene, endometrial bleeding
      associated factor (ebaf), whose strong expression in endometrium was associated
      with abnormal endometrial bleeding. In normal human endometrium, this gene was
      transiently expressed before and during menstrual bleeding. In situ hybridization
      showed that the mRNA of ebaf was expressed in the stroma without any significant
      mRNA expression in the endometrial glands or endothelial cells. The predicted
      protein sequence of ebaf showed homology with and structural features of the
      members of TGF-beta superfamily. Fluorescence in situ hybridization showed that
      the ebaf gene is located on human chromosome 1 at band q42.1. Thus, ebaf is a
      novel member of the TGF-beta superfamily and an endometrial tissue factor whose
      expression is associated with normal menstrual and abnormal endometrial bleeding.

PMID- 9153276
TI  - Vascular endothelial growth factor is an essential molecule for mouse kidney
      development: glomerulogenesis and nephrogenesis.
AB  - Homeostasis of body fluid is maintained by the kidneys, which contain two million
      glomeruli for blood filtration. A glomerulus is formed by growth of Bowman's
      capsule harmonized with a capillary during kidney development. The vascular
      endothelial growth factor (VEGF) is an essential angiogenic cytokine, and VEGF
      deficiency is known to be fatal in mice in early embryonic stages. As secretions
      of VEGF from cultured kidneys vary according to developmental stages, the role of
      VEGF in kidney development was studied in vivo by blocking the endogenous VEGF
      activity with antibody in newborn mice, in which most organs are already
      developed but kidneys are still developing. The antibody-treated animals showed
      normal growth but systemic edema. Vessel formation in the superficial renal
      cortex was disturbed, nephrogenic areas were diminished, and the number of
      developing nephrons decreased significantly. Many abnormal glomeruli, lacking
      capillary tufts, were observed in the antibody-treated mice, and VEGF expression
      in their Bowman's capsule showed a compensatory increase. These results suggest
      that VEGF mediates communication between the Bowman's capsule and capillary
      endothelial cells for developing a glomerulus as well as promoting nephrogenesis.
      In conclusion, VEGF is likely to be an essential molecule for kidney development,
      and especially for glomerulogenesis.

PMID- 9153274
TI  - Downregulation of cyclin-dependent kinase 2 activity and cyclin A promoter
      activity in vascular smooth muscle cells by p27(KIP1), an inhibitor of neointima
      formation in the rat carotid artery.
AB  - Abnormal proliferation of vascular smooth muscle cells (VSMCs) contributes to
      intimal hyperplasia during atherosclerosis and restenosis, but the endogenous
      cell cycle regulatory factors underlying VSMC growth in response to arterial
      injury are not well understood. In the present study, we report that
      downregulation of cyclin-dependent kinase 2 (cdk2) activity in serum-deprived
      VSMCs was associated with the formation of complexes between cdk2 and its
      inhibitory protein p27(KIP1) (p27). Ectopic overexpression of p27 in serum
      stimulated VSMCs resulted in the inhibition of cdk2 activity and repression of
      cyclin A promoter activity. Collectively, these findings indicate that p27 may
      contribute to VSMC growth arrest in vitro. Using the rat carotid model of balloon
      angioplasty, a marked upregulation of p27 was observed in injured arteries. High
      levels of p27 expression in the media and neointima correlated with
      downregulation of cdk2 activity at 2 wk after angioplasty, and adenovirus
      mediated overexpression of p27 in balloon-injured arteries attenuated neointimal
      lesion formation. Thus, the inhibition of cdk2 function and repression of cyclin
      A gene transcription through the induction of the endogenous p27 protein provides
      a mechanism for the inhibition of VSMC growth at late time points after
      angioplasty.

PMID- 9153277
TI  - Vitamin C blocks inflammatory platelet-activating factor mimetics created by
      cigarette smoking.
AB  - Cigarette smoking within minutes induces leukocyte adhesion to the vascular wall
      and formation of intravascular leukocyte-platelet aggregates. We find this is
      inhibited by platelet-activating factor (PAF) receptor antagonists, and
      correlates with the accumulation of PAF-like mediators in the blood of cigarette
      smoke-exposed hamsters. These mediators were PAF-like lipids, formed by
      nonenzymatic oxidative modification of existing phospholipids, that were distinct
      from biosynthetic PAF. These PAF-like lipids induced isolated human monocytes and
      platelets to aggregate, which greatly increased their secretion of IL-8 and
      macrophage inflammatory protein-1alpha. Both events were blocked by a PAF
      receptor antagonist. Similarly, blocking the PAF receptor in vivo blocked smoke
      induced leukocyte aggregation and pavementing along the vascular wall. Dietary
      supplementation with the antioxidant vitamin C prevented the accumulation of PAF
      like lipids, and it prevented cigarette smoke-induced leukocyte adhesion to the
      vascular wall and formation of leukocyte-platelet aggregates. This is the first
      in vivo demonstration of inflammatory phospholipid oxidation products and it
      suggests a molecular mechanism coupling cigarette smoke with rapid inflammatory
      changes. Inhibition of PAF-like lipid formation and their intravascular sequela
      by vitamin C suggests a simple dietary means to reduce smoking-related
      cardiovascular disease.

PMID- 9153278
TI  - Overexpression of the TGFbeta-regulated zinc finger encoding gene, TIEG, induces
      apoptosis in pancreatic epithelial cells.
AB  - Members of the TGFbeta family of peptides exert antiproliferative effects and
      induce apoptosis in epithelial cell populations. In the exocrine pancreas, these
      peptides not only regulate normal cell growth, but alterations in these pathways
      have been associated with neoplastic transformation. Therefore, the
      identification of molecules that regulate exocrine pancreatic cell proliferation
      and apoptotic cell death in response to TGFbeta peptides is necessary for a
      better understanding of normal morphogenesis as well as carcinogenesis of the
      pancreas. In this study, we have characterized the expression and function in
      exocrine pancreatic epithelial cells of the TGFbeta-inducible early gene (TIEG),
      a Kruppel-like zinc finger transcription factor encoding gene previously isolated
      from mesodermally derived osteoblastic cells. We demonstrate that this gene is
      expressed in both acinar and ductular epithelial cell populations from the
      exocrine pancreas. In addition, we show that the expression of TIEG is regulated
      by TGFbeta1 as an early response gene in pancreatic epithelial cell lines.
      Moreover, overexpression of TIEG in the TGFbeta-sensitive epithelial cell line
      PANC1 is sufficient to induce apoptosis. Together, these results support a role
      for TIEG in linking TGFbeta-mediated signaling cascades to the regulation of
      pancreatic epithelial cell growth.

PMID- 9153279
TI  - The critical role of tissue angiotensin-converting enzyme as revealed by gene
      targeting in mice.
AB  - Angiotensin-converting enzyme (ACE) generates the vasoconstrictor angiotensin II,
      which plays a critical role in maintenance of blood pressure in mammals. Although
      significant ACE activity is found in plasma, the majority of the enzyme is bound
      to tissues such as the vascular endothelium. We used targeted homologous
      recombination to create mice expressing a form of ACE that lacks the COOH
      terminal half of the molecule. This modified ACE protein is catalytically active
      but entirely secreted from cells. Mice that express only this modified ACE have
      significant plasma ACE activity but no tissue-bound enzyme. These animals have
      low blood pressure, renal vascular thickening, and a urine concentrating defect.
      The phenotype is very similar to that of completely ACE-deficient mice previously
      reported, except that the renal pathology is less severe. These studies strongly
      support the concept that the tissue-bound ACE is essential to the control of
      blood pressure and the structure and function of the kidney.

PMID- 9153280
TI  - Interferon-gamma is necessary for the expression of hypersensitivity pneumonitis.
AB  - Farmers lung disease is a common form of hypersensitivity pneumonitis (HP) and is
      characterized by inflammation and granuloma formation in the lung. Interferon
      gamma is important for the expression of granulomatous diseases caused by
      infectious agents; however, the role this mediator in regulating expression of
      the granulomatous response to inhaled antigen is not known. To evaluate this, we
      compared the response to inhaled antigen of mice that do not express the gene
      coding for interferon-gamma (GKO) with that of their normal littermates (WT). GKO
      and WT mice on a BALB/c background were exposed to 150 microg of the thermophilic
      bacteria Saccharopolyspora rectivirgula or saline alone, for three consecutive
      days a week, for 3 wk. After exposure to antigen, WT mice developed a marked
      granulomatous inflammation associated with an increase in lung weight and numbers
      of cells in bronchoalveolar lavage fluid (BAL). Although GKO mice also exhibited
      an increase in lung weight and numbers of cells in BAL fluid, they developed
      minimal inflammation and no granulomas after a similar exposure to antigen. To
      further evaluate if the lack of a response to antigen in GKO mice was due to lack
      of IFN-gamma, we replaced this mediator via intraperitoneal injections. When
      given replacement IFN-gamma, the GKO mice developed granulomatous inflammation in
      the lung. These studies show that IFN-gamma is essential for the expression of
      hypersensitivity pneumonitis.

PMID- 9153281
TI  - Identification of two mutations in human xanthine dehydrogenase gene responsible
      for classical type I xanthinuria.
AB  - Hereditary xanthinuria is classified into three categories. Classical xanthinuria
      type I lacks only xanthine dehydrogenase activity, while type II and molybdenum
      cofactor deficiency also lack one or two additional enzyme activities. In the
      present study, we examined four individuals with classical xanthinuria to
      discover the cause of the enzyme deficiency at the molecular level. One subject
      had a C to T base substitution at nucleotide 682 that should cause a CGA (Arg) to
      TGA (Ter) nonsense substitution at codon 228. The duodenal mucosa from the
      subject had no xanthine dehydrogenase protein while the mRNA level was not
      reduced. The two subjects who were siblings with type I xanthinuria were
      homozygous concerning this mutation, while another subject was found to contain
      the same mutation in a heterozygous state. The last subject who was also with
      type I xanthinuria had a deletion of C at nucleotide 2567 in cDNA that should
      generate a termination codon from nucleotide 2783. This subject was homozygous
      for the mutation and the level of mRNA in the duodenal mucosa from the subject
      was not reduced. Thus, in three subjects with type I xanthinuria, the primary
      genetic defects were confirmed to be in the xanthine dehydrogenase gene.

PMID- 9153282
TI  - Leptin secretion from adipose tissue in women. Relationship to plasma levels and
      gene expression.
AB  - The role of expression and secretion of the ob gene product, leptin, for the
      regulation of plasma leptin levels has been investigated in vitro using abdominal
      subcutaneous adipose tissue of 20 obese, otherwise healthy, and 11 nonobese
      women. Body mass index (BMI, mean+/-SEM; kg/m2) in the two groups was 41+/-2 and
      23+/-1, respectively. Fat cell volume was 815+/-55 pl in the obese and 320+/-46
      pl in the nonobese group. In the obese group, plasma leptin concentrations and
      adipose leptin mRNA (relative to gamma actin) were increased five and two times,
      respectively. Moreover, adipose tissue secretion rates per gram lipid weight or
      per fat cell number were also increased two and seven times, respectively, in the
      obese group. There were strong linear correlations (r = 0.6-0.8) between plasma
      leptin, leptin secretion, and leptin mRNA. All of these leptin measurements
      correlated strongly with BMI and fat cell volume (r = 0.7- 0.9). About 60% of the
      variation in plasma leptin could be attributed to variations in leptin secretion
      rate, BMI, or fat cell volume. We conclude that elevated circulating levels of
      leptin in obese women above all result from accelerated secretion rates of the
      peptide from adipose tissue because of increased ob gene expression. However,
      leptin mRNA, leptin secretion, and circulating leptin levels are all more closely
      related to the stored amount of lipids in the fat cells of adipose tissue than
      they are to an arbitrary division into obese versus nonobese.

PMID- 9153283
TI  - Identification of naturally processed T cell epitopes from glutamic acid
      decarboxylase presented in the context of HLA-DR alleles by T lymphocytes of
      recent onset IDDM patients.
AB  - Glutamic acid decarboxylase (GAD) has been defined as a major target antigen in
      insulin-dependent diabetes mellitus (IDDM). To identify the molecular ligands
      triggering a T cell response to GAD, a panel of human GAD65-specific T lymphocyte
      lines was generated from peripheral blood of three recent onset IDDM patients.
      All lines derived from a patient expressing the high-risk-conferring HLA-DR*0301/
      *0401 haplotypes recognized a single epitope localized between amino acid
      positions 270 and 283 of GAD65, a stretch that is located in close proximity to
      the homology region shared with Coxsackie virus P2-C protein. All lines with this
      specificity were restricted to the DRA, B1*0401 product of the DR4 haplotype.
      Analysis of the GAD-specific T cell response in a second patient homozygous for
      DR4 haplotypes demonstrated that the same DRA, B1*0401 allele selected T cells
      specific for a different determinant. The T cell response profile in a third
      patient showed that DR*1501/ *1601-encoding haplotypes could present at least
      three different epitopes to GAD65-specific T lymphocytes. One of these epitopes
      was presented by a DR allele associated with the resistance-conferring DRB1*1501
      haplotype. GAD-specific T cell lines could not be isolated from HLA class II
      matched normal individuals. Our data reveal that (a) the T cell response to GAD65
      is quite heterogenous in recent onset IDDM patients; (b) HLA-DR, not DQ, seems to
      be the principal restriction element used by T cells present at the onset of the
      disease; and (c) T cells responding to epitopes containing identical sequences to
      Coxsackie virus P2-C protein were not detected.

PMID- 9153284
TI  - Peroxisome proliferator-activated receptor gene expression in human tissues.
      Effects of obesity, weight loss, and regulation by insulin and glucocorticoids.
AB  - The peroxisome proliferator activated receptor (PPAR gamma) plays a key role in
      adipogenesis and adipocyte gene expression and is the receptor for the
      thiazolidinedione class of insulin-sensitizing drugs. The tissue expression and
      potential for regulation of human PPAR gamma gene expression in vivo are unknown.
      We have cloned a partial human PPAR gamma cDNA, and established an RNase
      protection assay that permits simultaneous measurements of both PPAR gamma1 and
      PPAR gamma2 splice variants. Both gamma1 and gamma2 mRNAs were abundantly
      expressed in adipose tissue. PPAR gamma1 was detected at lower levels in liver
      and heart, whereas both gamma1 and gamma2 mRNAs were expressed at low levels in
      skeletal muscle. To examine the hypothesis that obesity is associated with
      abnormal adipose tissue expression of PPAR gamma, we quantitated PPARgamma mRNA
      splice variants in subcutaneous adipose tissue of 14 lean and 24 obese subjects.
      Adipose expression of PPARgamma 2 mRNA was increased in human obesity (14.25
      attomol PPAR gamma2/18S in obese females vs 9.9 in lean, P = 0.003). This
      increase was observed in both male and females. In contrast, no differences were
      observed in PPAR gamma1/18S mRNA expression. There was a strong positive
      correlation (r = 0.70, P < 0.001) between the ratio of PPAR gamma2/gamma1 and the
      body mass index of these patients. We also observed sexually dimorphic expression
      with increased expression of both PPAR gamma1 and PPAR gamma2 mRNAs in the
      subcutaneous adipose tissue of women compared with men. To determine the effect
      of weight loss on PPAR gamma mRNA expression, seven additional obese subjects
      were fed a low calorie diet (800 Kcal) until 10% weight loss was achieved. Mean
      expression of adipose PPAR gamma2 mRNA fell 25% (P = 0.0250 after a 10% reduction
      in body weight), but then increased to pretreatment levels after 4 wk of weight
      maintenance. Nutritional regulation of PPAR gamma1 was not seen. In vitro
      experiments revealed a synergistic effect of insulin and corticosteroids to
      induce PPAR gamma expression in isolated human adipocytes in culture. We conclude
      that: (a) human PPAR gamma mRNA expression is most abundant in adipose tissue,
      but lower level expression of both splice variants is seen in skeletal muscle; to
      an extent that is unlikely to be due to adipose contamination. (b) RNA derived
      from adipose tissue of obese humans has increased expression of PPAR gamma 2
      mRNA, as well as an increased ratio of PPAR gamma2/gamma1 splice variants that is
      proportional to the BMI; (c) a low calorie diet specifically down-regulates the
      expression of PPAR gamma2 mRNA in adipose tissue of obese humans; (d) insulin and
      corticosteroids synergistically induce PPAR gamma mRNA after in vitro exposure to
      isolated human adipocytes; and (e) the in vivo modulation of PPAR gamma2 mRNA
      levels is an additional level of regulation for the control of adipocyte
      development and function, and could provide a molecular mechanism for alterations
      in adipocyte number and function in obesity.

PMID- 9153285
TI  - Stress response decreases NF-kappaB nuclear translocation and increases I
      kappaBalpha expression in A549 cells.
AB  - The stress response and stress proteins confer protection against diverse forms
      of cellular and tissue injury, including acute lung injury. The stress response
      can inhibit nonstress protein gene expression, therefore transcriptional
      inhibition of proinflammatory responses could be a mechanism of protection
      against acute lung injury. To explore this possibility, we determined the effects
      of the stress response on nuclear translocation of the transcription factor NF
      kappaB, an important regulator of proinflammatory gene expression. In A549 cells
      induction of the stress response decreased tumor necrosis factor-alpha (TNF
      alpha)-mediated NF-kappaB nuclear translocation. TNF-alpha initiates NF-kappaB
      nuclear translocation by causing dissociation of the inhibitory protein I
      kappaBalpha from NF-kappaB and rapid degradation of I-kappaBalpha. Prior
      induction of the stress response inhibited TNF-alpha-mediated dissociation of I
      kappaBalpha from NF-kappaB and subsequent degradation of I-kappaBalpha. Induction
      of the stress response also increased expression of I-kappaBalpha. We conclude
      that the stress response affects NFkappaB-mediated gene regulation by two
      independent mechanisms. The stress response stabilizes I-kappaBalpha and induces
      expression of I-kappaBalpha. The composite result of these two effects is to
      decrease NF-kappaB nuclear translocation. We speculate that the protective effect
      of the stress response against acute lung injury involves a similar effect on the
      I-kappaB/NF-kappaB pathway.

PMID- 9153286
TI  - Vascular estrogen receptors and endothelium-derived nitric oxide production in
      the mouse aorta. Gender difference and effect of estrogen receptor gene
      disruption.
AB  - The present study was designed to test the hypothesis that estrogen receptors
      (ER) in the blood vessel wall play a role in the modulation of the release of
      endothelium-derived nitric oxide (EDNO). Both basal and stimulated release of
      EDNO were determined in aortic rings isolated from female and male wild-type and
      male homozygous estrogen receptor knock-out (ERKO) mice. 125I-17beta-estradiol
      binding in aortic tissue showed significantly more high affinity cytosolic-
      nuclear-binding sites in male compared with female wildtype mice. Estrogen
      receptor transcripts were present in the aorta of male wild-type mice, but they
      were absent in male ERKO animals. Basal release of EDNO (determined by
      endothelium-dependent contraction caused by NG-nitro-arginine) was significantly
      higher in aorta of wild-type male mice compared with wild-type female mice, and
      significantly lower in the aorta of male ERKO compared with male wild-type mice.
      Acetylcholine-induced endothelium-dependent relaxation was similar in all groups
      studied. No difference was observed in the activity of calcium-dependent nitric
      oxide synthase in homogenates of lungs and brain taken from male wild-type and
      ERKO mice. These studies show a significant association between the number of
      estrogen receptors and basal release of EDNO in the aorta of mice, and suggest
      that decreased vascular estrogen receptor number may represent a novel risk
      factor for cardiovascular diseases.

PMID- 9153287
TI  - Human recombinant apolipoprotein E redirects lipopolysaccharide from Kupffer
      cells to liver parenchymal cells in rats In vivo.
AB  - Chylomicrons have been shown to protect mice and rats against a lethal dose of
      lipopolysaccharide and may serve as a therapeutic means to protect against
      endotoxemia. However, the requisite of isolation from human lymph hampers
      pharmaceutical application. Recently, we developed recombinant chylomicrons from
      commercially available lipids and human recombinant apolipoprotein E. The current
      study explored the effectiveness of these apoE-enriched emulsions in redirecting
      LPS from Kupffer cells to liver parenchymal cells. Upon injection into rats, 125I
      LPS rapidly and specifically associated with the liver (64.3+/-3.1% of the
      injected dose) and spleen (4.1+/-0.7%). The uptake of LPS by the spleen was four-
      to fivefold reduced upon incubation with the apoE-enriched emulsion or free apoE
      (P < 0.0001), but not with emulsion alone or Lipofundin. Within the liver, 125I
      LPS mainly associated with Kupffer cells. The uptake by Kupffer cells was eight-
      to ninefold reduced by the apoE-enriched emulsion or apoE alone (P < 0.01), and a
      19.6-fold increased uptake ratio by liver parenchymal cells over Kupffer cells
      was observed. The emulsion without apoE had no effect on the in vivo kinetics of
      LPS. LPS interacted selectively with the apoE moiety of the recombinant
      chylomicron. Emulsion-associated and free apoE bound approximately two molecules
      of LPS, possibly by its exposed hydrophilic domain involving arginine residues.
      We anticipate that the protecting effect of endogenous chylomicrons against LPS
      induced endotoxemia may result from the apoE moiety and that human recombinant
      apoE may serve as a therapeuticum to protect against endotoxemia.

PMID- 9153288
TI  - Factor Xa as an interface between coagulation and inflammation. Molecular mimicry
      of factor Xa association with effector cell protease receptor-1 induces acute
      inflammation in vivo.
AB  - Coagulation proteases were tested in a rat model of acute inflammation.
      Subplantar injection of Factor Xa (10-30 microg) produced a time- and dose
      dependent edema in the rat paw, and potentiated carrageenin-induced edema. In
      contrast, the homologous protease Factor IXa was ineffective. This inflammatory
      response was recapitulated by the Factor Xa sequence L83FTRKL88(G), which
      mediates ligand binding to effector cell protease receptor-1 (EPR-1), while a
      control scrambled peptide did not induce edema in vivo. Conversely, injection of
      the EPR-1-derived peptide S123PGKPGNQNSKNEPP137 (corresponding to the receptor
      binding site for Factor Xa) inhibited carrageenin-induced rat paw edema, while
      the adjacent EPR-1 sequence P136PKKRERERSSHCYP150 was without effect. EPR-1
      Factor Xa-induced inflammation was characterized by fast onset and prominent
      perivascular accumulation of activated and degranulated mast cells, was inhibited
      by the histamine/serotonin antagonists cyproheptadine and methysergide, but was
      unaffected by the thrombin-specific inhibitor, Hirulog. These findings suggest
      that through its interaction with EPR-1, Factor Xa may function as a mediator of
      acute inflammation in vivo. This pathway may amplify both coagulation and
      inflammatory cascades, thus contributing to the pathogenesis of tissue injury in
      vivo.

PMID- 9153289
TI  - Developmental regulation, expression, and apoptotic potential of galectin-9, a
      beta-galactoside binding lectin.
AB  - Galectin-9, a beta-galactoside binding lectin, has recently been isolated from
      murine embryonic kidney. In this study, its biological functions and expression
      in embryonic, newborn, and adult mice tissues were investigated. By Northern blot
      analyses, it was found widely distributed and its expression was developmentally
      regulated. In situ hybridization studies revealed an accentuated expression of
      galectin-9 in liver and thymus of embryonic mice. In postnatal mice, antigalectin
      9 immunoreactivity was observed in various tissues, including thymic epithelial
      cells. The high expression of galectin-9 in the thymus led us to investigate its
      role in the clonal deletion of thymocytes. Fusion proteins were generated, which
      retained lactose-binding activity like the endogenous galectin-9. Galectin-9, at
      2.5 microM concentration, induced apoptosis in approximately 30% of the
      thymocytes, as assessed by terminal deoxytransferase-mediated dUTP nick end
      labeling method. The apoptotic effect was dose dependent and lactose inhibitable.
      At higher concentrations, it induced homotypic aggregation of the thymocytes.
      Electron microscopy revealed approximately 60% of the thymocytes undergoing
      apoptosis in the presence of galectin-9. By immunofluorescence microscopy, some
      of the thymocytes undergoing apoptosis had plasmalemmal bound galectin-9.
      Galectin-9 failed to induce apoptosis in hepatocytes. Taken together, these
      findings indicate that galectin-9, a developmentally regulated lectin, plays a
      role in thymocyte-epithelial interactions relevant to the biology of the thymus.

PMID- 9153290
TI  - Pituitary-directed leukemia inhibitory factor transgene forms Rathke's cleft
      cysts and impairs adult pituitary function. A model for human pituitary Rathke's
      cysts.
AB  - Leukemia inhibitory factor (LIF) and LIF receptors are expressed in
      adenohypophyseal cells and LIF regulates pituitary hormone transcription and cell
      replication in vitro. Therefore, transgenic mice expressing pituitary-directed
      LIF driven by the rat growth hormone (GH) promoter were generated to evaluate the
      impact of LIF on pituitary development. Three founders were established with
      diminished linear growth and body weight (57-65% of wild type [WT]), and intense
      anterior pituitary LIF immunoreactivity. Cystic cavities observed in pituitary
      anterior lobes were lined by cuboidal, ciliated epithelial cells, focally
      immunopositive for cytokeratin and S-100 protein and immunonegative for
      adenohypophyseal hormones. Transgenic pituitaries showed decreased GH (40%) and
      prolactin (PRL) (26%) cells, and decreased GH and PRL mRNAs by in situ
      hybridization. ACTH cells increased 2.2-fold, whereas gonadotrophs and
      thyrotrophs were unchanged. Serum GH was undetectable (< 0.78 ng/ml), PRL levels
      were one third of WT (P < 0.05), IGF-I levels were 30% of WT (P < 0. 001), and T4
      was normal. 10 human pituitary Rathke's cysts studied all showed conclusive LIF
      immunoreactivity in cyst-lining cells. Thus, intrapituitary murine LIF
      overexpression causes cystic invaginations from the anterior wall of Rathke's
      cleft, suggesting failed differentiation of Rathke's epithelium to hormone
      secreting cells. Arrested murine pituitary maturation with formation of pituitary
      Rathke's cleft cysts, GH deficiency, and short stature provide a model to study
      human Rathke's cyst pathogenesis.

PMID- 9153291
TI  - Isoform switching of type IV collagen is developmentally arrested in X-linked
      Alport syndrome leading to increased susceptibility of renal basement membranes
      to endoproteolysis.
AB  - Normal glomerular capillaries filter plasma through a basement membrane (GBM)
      rich in alpha3(IV), alpha4(IV), and alpha5(IV) chains of type IV collagen. We now
      show that these latter isoforms are absent biochemically from the glomeruli in
      patients with X-linked Alport syndrome (XAS). Their GBM instead retain a fetal
      distribution of alpha1(IV) and alpha2(IV) isoforms because they fail to
      developmentally switch their alpha-chain use. The anomalous persistence of these
      fetal isoforms of type IV collagen in the GBM in XAS also confers an unexpected
      increase in susceptibility to proteolytic attack by collagenases and cathepsins.
      The incorporation of cysteine-rich alpha3(IV), alpha4(IV), and alpha5(IV) chains
      into specialized basement membranes like the GBM may have normally evolved to
      protectively enhance their resistance to proteolytic degradation at the site of
      glomerular filtration. The relative absence of these potentially protective
      collagen IV isoforms in GBM from XAS may explain the progressive basement
      membrane splitting and increased damage as these kidneys deteriorate.

PMID- 9153292
TI  - Mechanisms permitting nephrotic patients to achieve nitrogen equilibrium with a
      protein-restricted diet.
AB  - Clinical experience suggests nephrotic patients are at risk for malnutrition. To
      determine if nephrotic patients can adapt successfully to a protein-restricted
      diet, nephrotic (glomerular filtration rate, 52+/-15 ml/min; urinary protein
      [Uprot.], 7.2+/-2.2 grams/d) and control subjects completed a crossover
      comparison of diets providing 0.8 or 1.6 grams protein (plus 1 gram protein/gram
      Uprot.) and 35 kcal per kg per day. Nitrogen balance (BN) was determined and
      whole body protein turnover measured during fasting and feeding using intravenous
      -[1-13C]leucine and intragastric -[5,5, 5- 2H3]leucine. BN was positive in both
      nephrotic and control subjects consuming either diet and rates of whole-body
      protein synthesis, protein degradation, and leucine oxidation did not differ
      between groups. In both nephrotic and control subjects anabolism was due to a
      suppression of whole-body protein degradation and stimulation of protein
      synthesis during feeding. The principal compensatory response to dietary protein
      restriction was a decrease in amino acid oxidation and this response was the same
      in both groups. With the low protein diet leucine oxidation rates during feeding
      correlated inversely with Uprot. losses (r = -0.83; P < 0. 05). CONCLUSIONS: (a)
      a diet providing 0.8 gram protein (plus 1 gram protein/gram Uprot.) and 35 kcal
      per kg per day maintains BN in nephrotic patients; (b) nephrotic patients
      activate normal anabolic responses to dietary protein restriction (suppression of
      amino acid oxidation) and feeding (stimulation of protein synthesis and
      inhibition of protein degradation); (c) the inverse correlation between leucine
      oxidation and Uprot. losses suggests that proteinuria is a stimulus to conserve
      dietary essential amino acids.

PMID- 9153293
TI  - Analysis of the human VH gene repertoire. Differential effects of selection and
      somatic hypermutation on human peripheral CD5(+)/IgM+ and CD5(-)/IgM+ B cells.
AB  - To analyze the immunoglobulin repertoire of human IgM+ B cells and the CD5(+) and
      CD5(-) subsets, individual CD19(+)/ IgM+/CD5(+) or CD5(-) B cells were sorted and
      non-productive as well as productive VH gene rearrangements were amplified from
      genomic DNA and sequenced. In both subsets, the VH3 family was overrepresented
      largely as a result of preferential usage of a small number of specific
      individual family members. In the CD5(+) B cell subset, all other VH families
      were found at a frequency expected from random usage, whereas in the CD5(-)
      population, VH4 appeared to be overrepresented in the nonproductive repertoire,
      and also negatively selected since it was found significantly less often in the
      productive compared to the nonproductive repertoire; the VH1 family was
      significantly diminished in the productive rearrangements of CD5(-) B cells. 3
      23/DP-47 was the most frequently used VH gene segment and was found significantly
      more often than expected from random usage in productive rearrangements of both
      CD5(+) and CD5(-) B cells. Evidence for selection based on the D segment and the
      JH gene usage was noted in CD5(+) B cells. No differences were found between the
      B cell subsets in CDR3 length, the number of N-nucleotides or evidence of
      exonuclease activity. Somatically hypermutated VHDJH rearrangements were
      significantly more frequent and extensive in CD5(-) compared to CD5(+) IgM+ B
      cells, indicating that IgM+ memory B cells were more frequent in the CD5(-) B
      cell population. Of note, the frequency of specific VH genes in the mutated
      population differed from that in the nonmutated population, suggesting that
      antigen stimulation imposed additional biases on the repertoire of IgM+ B cells.
      These results indicate that the expressed repertoire of IgM+ B cell subsets is
      shaped by recombinational bias, as well as selection before and after antigen
      exposure. Moreover, the influences on the repertoires of CD5(+) and CD5(-) B
      cells are significantly different, suggesting that human peripheral blood CD5(+)
      and CD5(-) B cells represent different B cell lineages, with similarities to
      murine B-1a and B-2 subsets, respectively.

PMID- 9153294
TI  - A decline in myometrial nitric oxide synthase expression is associated with labor
      and delivery.
AB  - The mechanisms that maintain relative uterine quiescence during pregnancy remain
      largely unknown. A possible role for nitric oxide has recently emerged, however,
      the expression of nitric oxide synthase within human myometrium at midgestation,
      a time when the uterus is normally quiescent, has not been investigated. The
      purpose of this study was to identify cell types in human myometrium that contain
      inducible nitric oxide synthase (iNOS), and to examine changes in its expression
      during pregnancy and labor. We found that iNOS is expressed in smooth muscle
      cells of pregnant myometrium. Expression of iNOS was highest in myometrium of
      preterm not-in-labor patients. At term, iNOS expression fell by 75%, and was
      barely detectable in preterm in-labor or term in-labor specimens. There was no
      staining in the myocytes of nonpregnant myometrium. Western blotting also
      revealed a similar pattern of changes in iNOS expression. In summary, iNOS
      expression in the myocytes of human myometrium is increased greatly during
      pregnancy, and declines towards term or with labor. Significantly, preterm
      inlabor patients also had a large decline in iNOS expression. These data suggest
      that changes in myometrial iNOS expression may participate in the regulation of
      uterine activity during human pregnancy.

PMID- 9153295
TI  - Inhibition of osteolytic bone metastasis of breast cancer by combined treatment
      with the bisphosphonate ibandronate and tissue inhibitor of the matrix
      metalloproteinase-2.
AB  - Multiple steps are involved in the metastasis of cancer cells from primary sites
      to distant organs. These steps should be considered in the design of
      pharmacologic approaches to prevent or inhibit the metastatic process. In the
      present study, we have compared the effects of inhibiting several steps involved
      in the bone metastatic process individually with inhibition of both together. The
      steps we chose were matrix metalloproteinase (MMP) secretion, likely involved in
      tumor cell invasion, and osteoclastic bone resorption, the final step in the
      process. We used an experimental model in which inoculation of human estrogen
      independent breast cancer MDA-231 cells into the left cardiac ventricle of female
      nude mice causes osteolytic lesions in bone. To inhibit cancer invasiveness, the
      tissue inhibitor of the MMP-2 (TIMP-2), which is a natural inhibitor of MMPs, was
      overexpressed in MDA-231 cells. To inhibit bone resorption, a potent
      bisphosphonate, ibandronate (4 microg/mouse) was daily administered
      subcutaneously. Nude mice received either; (a) nontransfected MDA-231 cells; (b)
      nontransfected MDA231 cells and ibandronate; (c) TIMP-2-transfected MDA-231
      cells; or (d) TIMP-2-transfected MDA-231 cells and ibandronate. In mice from
      group a, radiographs revealed multiple osteolytic lesions. However, in mice from
      group b or group c, osteolytic lesions were markedly decreased. Of particular
      note, in animals from group d receiving both ibandronate and TIMP-2-transfected
      MDA-231 cells, there were no radiologically detectable osteolytic lesions.
      Survival rate was increased in mice of groups c and d. There was no difference in
      local enlargement in the mammary fat pad between nontransfected and TIMP-2
      transfected MDA-231 cells. These results suggest that inhibition of both MMPs and
      osteoclastic bone resorption are more efficacious treatment for prevention of
      osteolytic lesions than either alone, and suggest that when therapies are
      designed based on the uniqueness of the bone microenvironment and combined with
      several common steps in the metastatic process, osteolytic bone metastases can be
      more efficiently and selectively inhibited.

PMID- 9153296
TI  - Tumor necrosis factor alpha (TNFalpha) promotes growth of virulent Mycobacterium
      tuberculosis in human monocytes iron-mediated growth suppression is correlated
      with decreased release of TNFalpha from iron-treated infected monocytes.
AB  - The human immune response to Mycobacterium tuberculosis is not well
      characterized. To better understand the cellular immune response to tuberculosis,
      a human mononuclear phagocyte culture system using a low-infecting inoculum of M.
      tuberculosis to mimic in vivo conditions was developed. Using this system,
      monocytes treated with IFNgamma/TNFalpha/ calcitriol (CytD) were permissive for
      the growth of virulent M. tuberculosis. In the presence of iron, however, these
      monocytes suppressed the growth of M. tuberculosis. The enhanced permissiveness
      of CytD-preincubated monocytes was found to be due to TNFalpha, however, the
      ability of iron to suppress M. tuberculosis growth also required preincubation
      with TNFalpha. Iron-mediated growth suppression was correlated with selective
      suppression of TNFalpha release from infected monocytes. In addition, removal of
      TNFalpha from CytD-treated monocytes 2 d after infection mimicked the suppressive
      effect of iron, suggesting that iron may also be decreasing monocyte sensitivity
      to exogenously added TNFalpha. In the absence of iron, permissive, CytD-treated
      monocytes formed large infected cellular aggregates. With iron treatment,
      aggregation was suppressed, suggesting that the iron-suppressive effect on M.
      tuberculosis growth may be related to suppression of monocyte aggregation and
      diminished cell-to-cell spread of M. tuberculosis. The results of this study
      indicate that TNFalpha preincubation is required for human monocytes to exert an
      iron-mediated suppressive effect on M. tuberculosis growth. In the absence of
      iron, however, the continued presence of TNFalpha has a growth-promoting effect
      on M. tuberculosis in human monocytes. Iron may be an important early modulator
      of M. tuberculosis growth via its effects on TNFalpha.

PMID- 9153297
TI  - Identification and expression of acid beta-glucosidase mutations causing severe
      type 1 and neurologic type 2 Gaucher disease in non-Jewish patients.
AB  - Gaucher disease, the most prevalent lysosomal storage disease, occurs in three
      subtypes, all resulting from mutations in the acid beta-glucosidase gene.
      Molecular studies in five severely affected type 1 and two type 2 Gaucher disease
      patients of non-Jewish descent identified six new mutations: K74X, W179X, G195E,
      S271N, V352L, and a two-base deletion in exon 10 (1450del2). Two additional
      mutations identified in these patients (R48W and G202R) have been reported
      previously, but were not expressed or characterized. Heterologous expression in
      Sf 9 cells using the baculovirus system revealed that the missense mutations,
      R48W and V352L, had 14 and 7%, respectively, of the specific activity based on
      cross-reacting immunologic material expressed by the normal allele. In contrast,
      the G195E, G202R, and S271N mutant alleles were more severely compromised with
      only 1-2% of the normal expressed specific activity based on cross-reacting
      immunologic material. Structural distortion at the active site was probed by
      comparing the interaction of the mutant enzymes with active site-directed
      inhibitors (castanospermine, conduritol B epoxide and deoxynojirimycin). R48W,
      G202R, and S271N were normally inhibited, whereas the V352L and G195E mutant
      enzymes had significantly decreased binding affinity. These mutations further
      expand the genetic heterogeneity in the lesions causing Gaucher disease types 1
      and 2, and further delineate genotype/phenotype correlations and functional
      domains within the acid beta-glucosidase gene.

PMID- 9153298
TI  - Hypoglycemic effect of insulin-like growth factor-1 in mice lacking insulin
      receptors.
AB  - We have investigated the metabolic actions of recombinant human IGF-1 in mice
      genetically deficient of insulin receptors (IR-/-). After intraperitoneal
      administration, IGF-1 caused a prompt and sustained decrease of plasma glucose
      levels in IR-/- mice. Plasma free fatty acid concentrations were unaffected.
      Interestingly, the effects of IGF-1 were identical in normal mice (IR+/+) and in
      IR-/- mice. Despite decreased glucose levels, IR-/- mice treated with IGF-1 died
      within 2-3 d of birth, like sham-treated IR-/- controls. In skeletal muscle, IGF
      1 treatment caused phosphorylation of IGF-1 receptors and increased the levels of
      the phosphatidylinositol-3-kinase p85 subunit detected in antiphosphotyrosine
      immunoprecipitates, consistent with the possibility that IGF-1 stimulates glucose
      uptake in a phosphatidylinositol-3-kinase-dependent manner. IGF-1 receptor
      phosphorylation and coimmunoprecipitation of phosphatidylinositol3-kinase by
      antiphosphotyrosine antibodies was also observed in liver, and was associated
      with a decrease in mRNA levels of the key gluconeogenetic enzyme
      phosphoenolpyruvate carboxykinase. Thus, the effect of IGF-1 on plasma glucose
      levels may be accounted for by increased peripheral glucose use and by inhibition
      of hepatic gluconeogenesis. These data indicate that IGF-1 can mimic insulin's
      effects on glucose metabolism by acting through its own receptor. The failure of
      IGF-1 to rescue the lethal phenotype due to lack of insulin receptors suggests
      that IGF-1 receptors cannot effectively mediate all the metabolic actions of
      insulin receptors.

PMID- 9153300
TI  - Distribution of topoisomerase II-mediated cleavage sites and relation to
      structural and functional landmarks in 830 kb of Drosophila DNA.
AB  - The pattern of sites for cleavage mediated by topoisomerase II was determined in
      830 kb of cloned DNA from the Drosophila X chromosome, with the objectives of
      comparing it with mapped structural and functional landmarks and examining if the
      correlations with such landmarks reported in individual loci can be generalized
      to a region approximately 100 times longer. The relative frequencies of
      topoisomerase II cleavage sites in 247 restriction fragments from 67 clones were
      quantified by hybridization with probes prepared from DNA fragments which abutted
      all cleavage sites in each clone, selected through the covalently bound
      topoisomerase II subunit; the specificity and quantitative nature of this method
      were demonstrated using a plasmid DNA model. The 12 restriction fragments with
      strong nuclear scaffold attachment (SAR) activity, of which seven possess
      autonomous replication (ARS) activity, show statistically strong coincidence or
      contiguity ( P </=0.11) with regions of high topoisomerase II cleavage site
      frequency. These regions show no correlation with repetitive sequence or A/T or
      C/G content and some extend over >10 kb; their sensitivity is therefore unlikely
      to be due to alternating purine-pyrimidine repeats or regions of Z conformation,
      which are preferred motifs. The hypothesis that they possess intrinsic curvature
      is consistent with the similarity of their length and spacing to regions of
      predicted curvature in the 315 kb DNA of Saccharomyces cerevisiae chromosome III
      and with the reported strong binding preference of topoisomerase II for curved
      DNA. The topoisomerase II cleavage pattern in this DNA further shows that its
      relationships to functional properties seen in individual loci, especially to
      MAR/SAR and ARS activity and to the restricted accessibility of DNA to
      topoisomerase II in vivo, can be generalized to much longer regions of the
      genome.

PMID- 9153299
TI  - Grapefruit juice increases felodipine oral availability in humans by decreasing
      intestinal CYP3A protein expression.
AB  - The increase in oral availability of felodipine and other commonly used
      medications when taken with grapefruit juice has been assumed to be due to
      inhibition of CYP3A4, a cytochrome P450 that is present in liver and intestine.
      To evaluate the effect of repeated grapefruit juice ingestion on CYP3A4
      expression, 10 healthy men were given 8 oz of grapefruit juice three times a day
      for 6 d. Before and after receiving grapefruit juice, small bowel and colon
      mucosal biopsies were obtained endoscopically, oral felodipine kinetics were
      determined, and liver CYP3A4 activity was measured with the [14C N-methyl]
      erythromycin breath test in each subject. Grapefruit juice did not alter liver
      CYP3A4 activity, colon levels of CYP3A5, or small bowel concentrations of P
      glycoprotein, villin, CYP1A1, and CYP2D6. In contrast, the concentration of
      CYP3A4 in small bowel epithelia (enterocytes) fell 62% (P = 0.0006) with no
      corresponding change in CYP3A4 mRNA levels. In addition, enterocyte
      concentrations of CYP3A4 measured before grapefruit juice consumption correlated
      with the increase in Cmax when felodipine was taken with either the 1st or the
      16th glass of grapefruit juice relative to water (r = 0. 67, P = 0.043, and r =
      0.71, P = 0.022, respectively). We conclude that a mechanism for the effect of
      grapefruit juice on oral felodipine kinetics is its selective downregulation of
      CYP3A4 in the small intestine.

PMID- 9153301
TI  - Recognition of DNA by single-chain derivatives of the phage 434 repressor: high
      affinity binding depends on both the contacted and non-contacted base pairs.
AB  - Single-chain derivatives of the phage 434 repressor, termed single-chain
      repressors, contain covalently dimerized DNA-binding domains (DBD) which are
      connected with a peptide linker in a head-to-tail arrangement. The prototype RR69
      contains two wild-type DBDs, while RR*69 contains a wild-type and an engineered
      DBD. In this latter domain, the DNA- contacting amino acids of thealpha3 helix of
      the 434 repressor are replaced by the corresponding residues of the related P22
      repressor. We have used binding site selection, targeted mutagenesis and binding
      affinity studies to define the optimum DNA recognition sequence for these single
      chain proteins. It is shown that RR69 recognizes DNA sequences containing the
      consensus boxes of the 434 operators in a palindromic arrangement, and that RR*69
      optimally binds to non-palindromic sequences containing a 434 operator box and a
      TTAA box of which the latter is present in most P22 operators. The spacing of
      these boxes, as in the 434 operators, is 6 bp. The DNA-binding of both single
      chain repressors, similar to that of the 434 repressor, is influenced indirectly
      by the sequence of the non-contacted, spacer region. Thus, high affinity binding
      is dependent on both direct and indirect recognition. Nonetheless, the single
      chain framework can accommodate certain substitutions to obtain altered DNA
      binding specificity and RR*69 represents an example for the combination of
      altered direct and unchanged indirect readout mechanisms.

PMID- 9153303
TI  - Mapping of Stat3 serine phosphorylation to a single residue (727) and evidence
      that serine phosphorylation has no influence on DNA binding of Stat1 and Stat3.
AB  - During their polypeptide ligand-induced activation Stats (signaltransducers
      andactivators oftranscription) 1 and 3 acquire, in addition to an obligatory
      tyrosine phosphorylation, phosphorylation on serine which boosts their
      transactivating potential [Wen, Z., Zhong, Z. and Darnell, J. E. Jr. (1995) Cell
      82, 241-250]. By examining phosphopeptide maps of wild-type and mutant protein we
      show here that the Stat3 serine phosphorylation, like the Stat1 serine
      phosphorylation, occurs on a single residue, serine 727. Neither the DNA binding
      of Stat1 nor Stat3 is demonstrably affected by the presence or absence of the
      serine phosphorylation. Thus the earlier demonstration that transcription is
      enhanced by the presence of the serine 727 residue likely occurs after DNA
      binding. These findings do not agree with earlier claims of excess serine to
      tyrosine phosphorylation in activated Stats 1 and 3 or to claims of more stable
      DNA binding of serine phosphorylated Stat dimers.

PMID- 9153304
TI  - Differential in vivo activation of the class II and class III snRNA genes by the
      POU-specific domain of Oct-1.
AB  - Many snRNA genes contain binding sites for the ubiquitous transcription factor
      Oct-1. In vitro studies have shown that this factor potentiates binding of an
      essential transcription factor (PTF) to the proximal sequence element (PSE) of
      snRNA genes, and activates transcription. Using Gal4 fusion proteins, I show here
      that the POU-specific region of the DNA-binding domain of Oct-1 is sufficient
      both to potentiate PTF binding in vitro and to transactivate pol II- and pol III
      dependent snRNA genes in vivo . A single amino acid change in this domain
      abrogates both activation and interaction with PTF. The N- and C-terminal regions
      of Oct-1 also activate transcription of both classes of snRNA genes. Wild-type
      levels of Pol II-dependent U2 expression require all activation domains, whereas
      efficient activation of the pol III-dependent 7SK and U6 genes is effected by the
      POU-specific domain alone. These results indicate that contacts between PTF and
      amino acids in the POU-specific domain of Oct-1 are critical for efficient
      transactivation of snRNA genes in vivo. The POU-specific domain of Oct-2A also
      activates these genes, but the N- and C-terminal domains are relatively inactive.

PMID- 9153302
TI  - A serine/arginine-rich nuclear matrix cyclophilin interacts with the C-terminal
      domain of RNA polymerase II.
AB  - The largest subunit of RNA polymerase II shows a striking difference in the
      degree of phosphorylation, depending on its functional state: initiating and
      elongating polymerases are unphosphorylated and highly phosphorylated
      respectively. Phosphorylation mostly occurs at the C-terminal domain (CTD), which
      consists of a repetitive heptapeptide structure. Using the yeast two-hybrid
      system, we have selected for mammalian proteins that interact with the
      phosphorylated CTD of mammalian RNA polymerase II. A prominent isolate,
      designated SRcyp/CASP10, specifically interacts with the CTD not only in vivo but
      also in vitro . It contains a serine/arginine-rich (SR) domain, similar to that
      found in the SR protein family of pre-mRNA splicing factors, which is required
      for interaction with the CTD. Most remarkably, the N-terminal region of SRcyp
      includes a peptidyl-prolyl cis - trans isomerase domain characteristic of
      immunophilins/cyclophilins (Cyp), a protein family implicated in protein folding,
      assembly and transport. SRcyp is a nuclear protein with a characteristic
      distribution in large irregularly shaped nuclear speckles and co-localizes
      perfectly with the SR domain-containing splicing factor SC35. Recent independent
      investigations have provided complementary data, such as an association of the
      phosphorylated form of RNA polymerase II with the nuclear speckles, impaired
      splicing in a CTD deletion background and inhibition of in vitro splicing by CTD
      peptides. Taken together, these data indicate that factors directly or indirectly
      involved in splicing are associated with the elongating RNA polymerases, from
      where they might translocate to the nascent transcripts to ensure efficient
      splicing, concomitant with transcription.

PMID- 9153305
TI  - Palindromic sequences preceding the terminator increase polymerase III template
      activity.
AB  - Four consecutive T residues in the sense strand are sufficient to terminate
      transcription by RNA polymerase III (pol III). Previously we observed that
      compared with this minimally sufficient terminator, five T residues immediately
      preceded by a palindromic sequence increases transcriptional expression both in
      vitro and in vivo, raising the question of whether a palindromic sequence has a
      role in pol III termination. Here we observe that site-directed mutations which
      eliminate the dyad symmetry of the palindromic sequence decrease transcriptional
      expression. Similar effects are observed whether dyad symmetry is eliminated in
      regions of the palindrome which are proximal or distal with respect to the
      terminator. Compensatory mutations at either site to restore dyad symmetry rescue
      transcriptional activity. These observations suggest that a higher order
      structure, such as a RNA hairpin, immediately preceding the terminator increases
      pol III transcriptional activity.

PMID- 9153306
TI  - Structure of the acceptor stem of Escherichia coli tRNA Ala: role of the G3.U70
      base pair in synthetase recognition.
AB  - The fidelity of translation of the genetic code depends on accurate tRNA
      aminoacylation by cognate aminoacyl-tRNA synthetases. Thus, each tRNA has
      specificity not only for codon recognition, but also for amino acid identity;
      this aminoacylation specificity is referred to as tRNA identity. The primary
      determinant of the acceptor identity of Escherichia coli tRNAAlais a wobble
      G3.U70 pair within the acceptor stem. Despite extensive biochemical and genetic
      data, the mechanism by which the G3.U70 pair marks the acceptor end of tRNAAla
      for aminoacylation with alanine has not been clarified at the molecular level.
      The solution structure of a microhelix derived from the tRNAAla acceptor end has
      been determined at high precision using a very extensive set of experimental
      constraints (approximately 32 per nt) obtained by heteronuclear multidimensional
      NMR methods. The tRNAAla acceptor end is overall similar to A-form RNA, but
      important differences are observed. The G3.U70 wobble pair distorts the
      conformation of the phosphodiester backbone and presents the functional groups of
      U70 in an unusual spatial location. The discriminator base A73 has extensive
      stacking overlap with G1 within the G1.C72 base pair at the end of the double
      helical stem and the -CCA end is significantly less ordered than the rest of the
      molecule.

PMID- 9153307
TI  - DNA strand transfer reactions catalyzed by vaccinia topoisomerase: hydrolysis and
      glycerololysis of the covalent protein-DNA intermediate.
AB  - Vaccinia topoisomerase forms a covalent protein-DNA intermediate at sites
      containing the sequence 5'-CCCTT. The T nucleotide is linked via a 3'
      phosphodiester bond to Tyr-274 of the enzyme. Here, we report that the enzyme
      catalyzes hydrolysis of the covalent intermediate, resulting in formation of a 3'
      phosphate-terminated DNA cleavage product. The hydrolysis reaction is pH
      dependent (optimum pH = 9.5) and is slower, by a factor of 10(-5), than the rate
      of topoisomerase-catalyzed strand transfer to a 5'-OH terminated DNA acceptor
      strand. Mutants of vaccinia topoisomerase containing serine or threonine in lieu
      of the active site Tyr-274 form no detectable covalent intermediate and catalyze
      no detectable DNA hydrolysis. This suggests that hydrolysis occurs subsequent to
      formation of the covalent protein-DNA adduct and not via direct attack by water
      on DNA. Vaccinia topoisomerase also catalyzes glycerololysis of the covalent
      intermediate. The rate of glycerololysis is proportional to glycerol
      concentration and is optimal at pH 9.5.

PMID- 9153308
TI  - Cyclin ET, a new splice variant of human cyclin E with a unique expression
      pattern during cell cycle progression and differentiation.
AB  - Cyclin E is the regulatory subunit of the cdc2-related protein kinase cdk2 and is
      a rate limiting factor for the entry into S phase. To date, cyclin E is the only
      cyclin for which alternative splicing has been described. We report here the
      isolation of a new splice variant of cyclin E, termed cyclin ET, which has an
      internal deletion of 45 amino acids compared with the full-length cyclin E
      protein. Even though cyclin ETcontains an intact cyclin box, it is unable to
      complement a triple cln mutant strain of Saccharomyces cerevisiae or to interfere
      with rescue by cyclin E, indicating that an intact cyclin box is functionally
      insufficient. The expression pattern of cyclin ET during cell cycle entry,
      progression and differentiation differs from that of cyclin E. Thus, ET
      expression precedes that of the other isoforms during the G0-->S progression; it
      shows a sharp peak in early G1 in cells released from a mitotic block and is
      strongly down-regulated in terminally differentiated myeloid cells. These
      observations point to different functions for cyclin ET and E and show for the
      first time that the alternative splicing of cyclin E is a regulated mechanism
      governed by the cell cycle and differentiation.

PMID- 9153309
TI  - Functional characterization of the T4 DNA ligase: a new insight into the
      mechanism of action.
AB  - ATP-dependent DNA ligases are essential enzymes in both DNA replication and DNA
      repair processes. Here we report a functional characterization of the T4 DNA
      ligase. One N-terminal and two C-terminal deletion mutants were expressed in
      Escherichia coli as histidine- tagged proteins. An additional mutant bore a
      substitution of Lys159 in the active site that abolished ATP binding. All the
      proteins were tested in biochemical assays for ATP-dependent self-adenylation,
      DNA binding, nick joining, blunt-end ligation and AMP- dependent DNA relaxation.
      From this analysis we conclude that binding to DNA is mediated by sequences at
      both protein ends and plays a key role in the reaction. The enzyme establishes
      two different complexes with DNA: (i) a transient complex (T.complex) involving
      the adenylated enzyme; (ii) a stable complex (S.complex) requiring the
      deadenylated T4 DNA ligase. The formation of an S. complex seems to be relevant
      during both blunt-end ligation and DNA relaxation. Moreover the inactive His
      K159L substitution mutant, although unable to self-adenylate, still possesses AMP
      dependent DNA nicking activity.

PMID- 9153310
TI  - Specific binding of sso II DNA methyltransferase to its promoter region provides
      the regulation of sso II restriction-modification gene expression.
AB  - The regulation of the Sso II restriction-modification system from Shigella sonnei
      was studied in vivo and in vitro . In lacZ fusion experiments, Sso II
      methyltransferase (M. Sso II) was found to repress its own synthesis but
      stimulate expression of the cognate restriction endonuclease (ENase). The N
      terminal 72 amino acids of M. Sso II, predicted to form a helix-turn-helix (HTH)
      motif, was found to be responsible for the specific DNA-binding and regulatory
      function of M. Sso II. Similar HTH motifs are predicted in the N-terminus of a
      number of 5-methylcytosine methyltransferases, particularly M. Eco RII, M.dcm and
      M. Msp I, of which the ability to regulate autogenously has been proposed. In
      vitro, the binding of M. Sso II to its target DNA was investigated using a
      mobility shift assay. M. Sso II forms a specific and stable complex with a 140 bp
      DNA fragment containing the promoter region of Sso II R-M system. The
      dissociation constant (Kd) was determined to be 1.5x10(-8) M. DNaseI footprinting
      experiments demonstrated that M. Sso II protects a 48-52 bp region immediately
      upstream of the M. Sso II coding sequence which includes the predicted -10
      promoter sequence of M. Sso II and the -10 and -35 sequences of R. Sso II.

PMID- 9153311
TI  - Synthesis and binding properties of conjugates between oligodeoxynucleotides and
      daunorubicin derivatives.
AB  - Conjugation of an anthracycline to a triplex-forming oligonucleotide (TFO) allows
      delivery of this drug to a specific DNA site, preserving the intercalation
      geometry of this class of anticancer agents. Conjugate 11, in which the TFO is
      linked via a hexamethylene bridge to the O-4 on the D ring of the anthraquinone
      moiety, affords the most stable triple helix, through intercalation of the planar
      chromophore between DNA bases and binding of both the TFO and the amino sugar to
      the major and the minor groove respectively.

PMID- 9153312
TI  - Structural characterization of three RNA hexanucleotide loops from the internal
      ribosome entry site of polioviruses.
AB  - Structural characteristics of three RNA hairpins from the internal ribosome entry
      site of poliovirus mRNAs have been determined in solution by NMR. Complete
      proton, phosphorus and carbon resonance assignments were made for the three 16 nt
      hairpins. The loop sequences, 5'-AAUCCA , AAACCA and GAACCA, have been shown to
      be essential for viral mRNA translation. NOESY spectra for the three oligomers
      were very similar indicating a common three dimensional structure. Stems were A
      type duplexes with C3'-endo sugar pucker. In the loops, sequential base stacking
      interactions were detected for all bases except between U8/A8 and C9, indicating
      a turn in the phosphodiester backbone at this point. Only one nucleotide, U8/A8,
      had a sugar pucker which deviated appreciably from C3'-endo. The final base in
      the loop, A11, exhibited an unusual gauche (-) gamma angle. An ensemble of 10
      structures calculated for one hairpin using restrained molecular dynamics shows
      that the first three bases of the loop are turned so as to be exposed to the
      exterior of the molecule, while the remaining three bases are in an orientation
      approximating a continuation of the stem helix. Structure calculations and NMR
      relaxation measurements indicate that the loop apex is subject to considerable
      local dynamics.

PMID- 9153313
TI  - Isolation and characterization of the Schizosaccharomyces pombe rhp9 gene: a gene
      required for the DNA damage checkpoint but not the replication checkpoint.
AB  - Checkpoint controls exist in eukaryotic cells to ensure that cells do not enter
      mitosis in the presence of DNA damage or unreplicated chromosomes. In
      Schizosaccharomyces pombe many of the checkpoint genes analysed to date are
      required for both the DNA damage and the replication checkpoints, an exception
      being chk1 . We report here on the characterization of nine new methylmethane
      sulphonate (MMS)-sensitive S.pombe mutants, one of which is defective in the DNA
      damage checkpoint but not the replication checkpoint. We have cloned and
      sequenced the corresponding gene. The predicted protein is most similar to the
      Saccharomyces cerevisiae Rad9 protein, having 46% similarity and 26% identity.
      The S.pombe protein, which we have named Rhp9 (Rad9 homologue in S. pombe) on the
      basis of structural and phenotypic similarity, also contains motifs present in
      BRCA1 and 53BP1. Deletion of the gene is not lethal and results in a DNA damage
      checkpoint defect. Epistasis analysis with other S.pombe checkpoint mutants
      indicates that rhp9 acts in a process involving the checkpoint rad genes and that
      the rhp9 mutant is phenotypically very similar to chk1.

PMID- 9153314
TI  - Functional and physical interaction between the yeast splicing factors Slu7 and
      Prp18.
AB  - We show that the requirement for Prp18 during the second step of actin pre-mRNA
      splicing in vitro is dictated by the distance between the branch point and the
      3'splice site. Prp18 is dispensable for splicing of precursor RNAs in which the
      interval between the branch point and 3'splice site is <12 nt. This resembles the
      requirement for another second step factor, Slu7. Excess Slu7 protein can bypass
      the need for Prp18 in vitro , suggesting that Slu7 and Prp18 function in a
      concerted manner. Physical interaction between Slu7 and Prp18 was demonstrated by
      using the two-hybrid assay. Deletion mutants of SLU7 were tested for their
      ability to support growth of a slu7 null strain. Removal of 199 amino acids from
      the N-terminus of the 382 amino acid Slu7 protein did not affect cell viability
      at 25 degrees C. A more extensive N-terminal deletion of 221 amino acids was
      lethal, as was a C-terminal deletion of 47 amino acids. Deleted versions of Slu7
      were also tested for interaction with Prp18 in the two-hybrid system. We define a
      segment of Slu7 from residue 200 to 224 that is necessary for interaction with
      Prp18.

PMID- 9153316
TI  - Heterogeneous terminal structure of Ty1 and Ty3 reverse transcripts.
AB  - A specific terminal structure of preintegrative DNA is required for transposition
      of retroviruses and LTR-retrotransposons. We have used an anchored PCR technique
      to map the 3'ends of DNA intermediates synthesized inside yeast Ty1 and Ty3
      retrotransposon virus-like particles. We find that, unlike retroviruses, Ty1
      replicated DNA does not have two extra base pairs at its 3'ends. In contrast some
      Ty3 preintegrative DNA molecules have two extra nucleotides at the 3'end of
      upstream and downstream long terminal repeats. Moreover we find that some
      molecules of replicated Ty3 DNA have more than two extra nucleotides at the 3'end
      of the upstream LTR. This observation could be accounted for by imprecise RNAse H
      cutting of the PPT sequence. The site of Ty1 and Ty3 plus-strand strong-stop DNA
      termination was also examined. Our results confirm that the prominent Ty1 and Ty3
      plus-strand strong-stop molecules harbor 12 tRNA templated bases but also show
      that some Ty1 and Ty3 plus-strand strong-stop DNA molecules harbor less tRNA
      templated bases. We propose that these less than full length plus-strand
      molecules could be active intermediates in Ty retrotransposon replication.

PMID- 9153315
TI  - DNA binding and phasing analyses of Tn5 transposase and a monomeric variant.
AB  - Both full-length Tn 5 transposase and a COOH-terminal truncated monomeric form of
      the protein,n369, have been shown to specifically bind end sequences at
      comparable affinities. In addition, both proteins distort the target sequence in
      a similar manner, as determined by a circular permutation assay. In this
      study,nEK54, a derivative ofn369 with a single amino acid substitution that
      significantly enhances binding activity, is used in further binding and bending
      studies along with full-length transposase. Phasing analysis has shown that
      distortion of the end sequences upon binding of full-length transposase and nEK54
      protein is due in part to a protein-induced bend oriented towards the major
      groove. Because the center of transposase-induced bending maps to the extreme
      leftward end of the 19 bp consensus sequence, we examined the possibility that
      optimal protein binding requires additional upstream nucleotide contacts.
      Experiments presented here show that 9-10 nucleotides are needed upstream of +1
      of the 19 bp sequence for efficient binding and this requirement can be met by
      either single-stranded or double-stranded DNA.

PMID- 9153317
TI  - Efficient in vitro inhibition of HIV-1 gag reverse transcription by peptide
      nucleic acid (PNA) at minimal ratios of PNA/RNA.
AB  - We have tested the inhibitory potential of peptide nucleic acid (PNA) on in vitro
      reverse transcription of the HIV-1 gag gene. PNA was designed to target different
      regions of the HIV-1 gag gene and the effect on reverse transcription by HIV-1,
      MMLV and AMV reverse transcriptases (RTs) was investigated. We found that a bis
      PNA (parallel antisense 10mer linked to antiparallel antisense 10mer) was
      superior to both the parallel antisense 10mer and antiparallel antisense 10mer in
      inhibiting reverse transcription of the gene, thus indicating triplex formation
      at the target sequence. A complete arrest of reverse transcription was obtained
      at approximately 6-fold molar excess of the bis-PNA with respect to the gag RNA.
      At this molar ratio we found no effect on in vitro translation of gag RNA. A
      15mer duplex-forming PNA was also found to inhibit reverse transcription at very
      low molar ratios of PNA/ gag RNA. Specificity of the inhibition of reverse
      transcription by PNA was confirmed by RNA sequencing, which revealed that all
      tested RTs were stopped by the PNA/RNA complex at the predicted site. We propose
      that the effect of PNA is exclusively due to steric hindrance, as we found no
      signs of RNA degradation that would indicate PNA-mediated RNase H activation of
      the tested RTs. In conclusion, PNA appears to have a potential to become a
      specific and efficient inhibitor of reverse transcription in vivo , provided
      sufficient intracellular levels are achievable.

PMID- 9153318
TI  - CCAAT binding NF-Y-TBP interactions: NF-YB and NF-YC require short domains
      adjacent to their histone fold motifs for association with TBP basic residues.
AB  - Both the TATA and CCAAT boxes are widespread promoter elements and their binding
      proteins, TBP and NF-Y, are extremely conserved in evolution. NF-Y is composed of
      three subunits, NF-YA, NF-YB and NF-YC, all necessary for DNA binding. NF-YB and
      NF-YC contain a putative histone-like motif, a domain also present in TBP
      associated factors (TAFIIs) and in the subunits of the transcriptional repressor
      NC2. Immunopurification of holo-TFIID with anti-TBP and anti-TAFII100 antibodies
      indicates that a fraction of NF-YB associates with TFIID in the absence of NF-YA.
      Sedimentation velocity centrifugation experiments confirm that two pools of NF
      YB, and most likely NF-YC, exist: one associated with NF-YA and binding to the
      CCAAT box; another involved in high molecular weight complexes. We started to
      dissect NF-Y-TFIID interactions by showing that: (i) NF-YB and NF-YC interact
      with TBP in solution, both separately and once bound to each other; (ii) short
      stretches of both NF-YB and NF-YC located within the evolutionary conserved
      domains, adjacent to the putative histone fold motifs, are necessary for TBP
      binding; (iii) TBP single amino acid mutants in the HS2 helix, previously shown
      to be defective in NC2 binding, are also unable to bind NF-YB and NF-YC.

PMID- 9153319
TI  - Antiparallel polypurine phosphorothioate oligonucleotides form stable triplexes
      with the rat alpha1(I) collagen gene promoter and inhibit transcription in
      cultured rat fibroblasts.
AB  - The rat alpha1(I) collagen promoter contains a unique polypurine-polypyrimidine
      sequence between -141 and -200 upstream of the transcription start site. The
      polypurine sequence from -171 to -200 (C2) is on the coding strand and the
      adjacent polypurine sequence from -141 to -170 (C1) is on the non-coding strand.
      Earlier we demonstrated triplex formation with a polypurine 30 nt parallel
      triplex-forming oligonucleotide (TFO) corresponding to C1 and inhibition of
      transcriptional activity of the rat alpha1(I) collagen promoter. In the present
      work we have tested triplex-forming abilities of shorter (18 nt) purine and
      pyrimidine TFOs in parallel and antiparallel orientation to the C1 purine
      sequence. Our results show that purine antiparallel TFOs formed triplexes with
      the highest binding affinities, while pyrimidine oligodeoxyribonucleotides (ODNs)
      did not show appreciable binding. Phosphorothioate modification of purine TFOs
      did not significantly reduce binding affinity. We also demonstrate that preformed
      triplexes are quite stable when precipitated with ethanol and resuspended in
      water. Further analysis was carried out using two purine phosphorothioate
      antiparallel TFOs, 158 APS and 164 APS, designed to bind to the promoter region
      from -141 to -158 and -147 to -164, respectively, which were found to form
      triplexes even under physiological conditions. DNase I footprinting experiments
      showed the ability of these TFOs to protect target sequences in the promoter
      region; both purine sequences (C1 and C2) were protected in the case of 158 APS.
      Transfection experiments using preformed triplexes with a reporter plasmid
      containing the collagen promoter sequence showed significant inhibition of
      transcription when compared with a control phosphorothioate ODN. The effect of
      164 APS was greater than that of 158 APS. These results indicate that this
      triplex strategy could be used in the down-regulation of collagen synthesis in
      cultured cells and offer the potential to control fibrosis in vivo.

PMID- 9153320
TI  - Differences in the phosphate oxygen requirements for self-cleavage by the
      extended and prototypical hammerhead forms.
AB  - The hammerhead self-cleaving motif occurs in a variety of RNAs that infect plants
      and consists of three non-conserved helices connected by a highly conserved
      central core. A variant hammerhead, called the extended hammerhead, is found in
      satellite 2 transcripts from a variety of caudate amphibians. The extended
      hammerhead has the same core as the prototypical hammerhead, but has unusually
      conserved sequence and structural elements in its peripheral helices. Here we
      present the results of a thiophosphate substitution interference analysis of the
      pro-Rp phosphate oxygen requirements in the two hammerhead forms. Five pro-Rp
      phosphate oxygens, all in the central core, were found to be important for self
      cleavage by the prototypical hammerhead. A similar set of core positions were
      important for self-cleavage by the extended hammerhead, but five non-core
      positions were also found to be important. Thiosubstitution at one of these
      positions had the most severe effect on self-cleavage observed in this analysis.
      Mn2+ did not alleviate this negative effect, indicating that this position was
      not part of a divalent cation binding site. We propose that novel tertiary
      interactions in the extended hammerhead help form the same catalytic core
      structure as that used by the prototypical plant virus hammerhead.

PMID- 9153321
TI  - Control of mouse U1 snRNA gene expression during in vitro differentiation of
      mouse embryonic stem cells.
AB  - Early in mouse development, two classes of U1 RNAs, mU1a and mU1b, are
      synthesized, but as development proceeds, transcription of the embryo-specific
      mU1b genes is selectively down-regulated to a barely detectable level. We show
      here that during in vitro differentiation of mouse embryonic stem (ES) cells,
      both exogenously introduced and endogenous U1b genes are subject to normal
      developmental regulation. Thus, ES cells represent a convenient isogenic system
      for studying the control of expression of developmentally regulated snRNA genes.
      Using this system, we have identified a region in the proximal 5'flanking region,
      located outside the PSE element, that is responsible for differential
      transcription of the mU1a and mU1b genes in both developing cells and transiently
      transfected NIH 3T3 cells.

PMID- 9153322
TI  - Isolating large nested deletions in bacterial and P1 artificial chromosomes by in
      vivo P1 packaging of products of Cre-catalysed recombination between the
      endogenous and a transposed loxP site.
AB  - A general approach for isolating large nested deletions in P1 artificial
      chromosomes (PACs) and bacterial artificial chromosomes (BACs) by retrofitting
      with a loxP site-containing Tn10 mini-transposon is described. Cre-mediated
      recombination between the loxP site existing in these clones and one introduced
      by transposition leads to deletions and inversions of the DNA between these
      sites. Large deletions are selectively recovered by transducing the retrofitted
      PAC or BAC clones with P1 phage. The requirement that both loxP sites in the
      cointegrate be packaged into a P1 head ensures that only large deletions are
      rescued. PCR analyses identified these deletions as products of legitimate
      recombination between loxP sites mediated by Cre protein. BACs produce deletions
      much more efficiently than PACs although the former cannot be induced to greater
      than unit copy in cells. Mammalian cell-responsive antibiotic resistance markers
      are introduced as part of the transposon into genomic clone deletions for
      subsequent functional analysis. Most importantly, the loxP site retrofitting and
      P1 transduction can be performed in the same bacterial host containing these
      clones directly isolated from PAC or BAC libraries. These procedures should
      facilitate physical and functional mapping of genes and regulatory elements in
      these large plasmids.

PMID- 9153323
TI  - Molecular and functional characterization of the promoter region of the mouse
      LDH/C gene: enhancer-assisted, Sp1-mediated transcriptional activation.
AB  - Molecular and functional studies of the LDH/C 5' upstream promoter elements were
      undertaken to elucidate the molecular mechanisms involved in temporal activation
      of LDH/C gene expression in differentiating germ cells. Ligation mediated-PCR (LM
      PCR) gene walking techniques were exploited to isolate a 2.1 kb fragment of the
      mouse LDH/C 5' promoter region. DNA sequence analysis of this isolated genomic
      fragment indicated that the mouse LDH/C promoter contained TATA and CCAT boxes as
      well as a GC-box (Sp1-binding site) situated upstream from the transcription
      start site. PCR-based in vivo DNase I footprinting analysis of a 600 bp fragment
      of the proximal LDH/C promoter region (-524/+38) in isolated mouse pachytene
      spermatocytes identified a single footprint over the GC-box motif. Three DNase I
      hypersensitive sites were also detectable in vivo, in a region containing
      (CT)n(GA)n repeats upstream from the CCAT box domain. Functional characterization
      of the promoter region was carried out in a rat C6 glioma cell line and an SV40
      transformed germ cell line (GC-1 spg) using wild-type and mutated LDH/C promoter
      CAT reporter constructs. These studies provide experimental evidence suggesting
      that transcriptional activation of the LDH/C promoter is regulated by enhancer
      mediated coactivation of the Sp1 proteins bound to the GC-box motif footprinted
      in vivo in pachytene spermatocytes.

PMID- 9153325
TI  - A rapid and efficient method for site-directed mutagenesis using one-step overlap
      extension PCR.
AB  - A rapid method is described to efficiently perform site-directed mutagenesis
      based on overlap extension polymerase chain reaction (OE-PCR). Two template DNA
      molecules in different orientations relative to only one universal primer were
      amplified in parallel. By choosing a high dilution of mutagenic primers it was
      possible to run an overlap extension PCR in only one reaction without
      purification of intermediate products. This method which we have named one-step
      overlap extension PCR (OOE-PCR) can in principle be applied to every DNA fragment
      which can be cloned into a multiple cloning site of any common cloning vector.

PMID- 9153324
TI  - AFM analysis of DNA-protamine complexes bound to mica.
AB  - A novel method for reconstituting sperm chromatin was used to investigate how
      protamine 1 condenses DNA. Complexes formed in vitro using linearized plasmid DNA
      were imaged and measured by atomic force microscopy (AFM). The structures formed
      were found to be highly dependent on the sample preparation method used for
      reconstitution. Interstrand, side-by-side fasiculation of DNA and toroidal-like
      structures only 1-2 DNA diameters thick were observed for complexes formed in
      solution following direct mixing of the DNA and protamine. Large chromatin
      aggregates were also observed on the mica. However, if the DNA was first allowed
      to attach to the mica prior to addition of the protamine, well-defined toroidal
      complexes were formed without any observed DNA fasiculation or aggregate
      formation. The diameter of the toroids measured 30.6-50.2 nm (mean 39.4 nm). The
      dimensions of these structures indicate that the condensed DNA is stacked
      vertically by four to five turns, with each coil containing as little as 360-370
      bp of 'B'-form DNA. This approach for preparing and imaging DNA-protamine
      complexes permits the analysis of intermediate structures 'trapped' on the mica
      as partially formed toruses of nucleoprotamine.

PMID- 9153326
TI  - Simultaneous loading of 200 sample lanes for DNA sequencing on vertical and
      horizontal, standard and ultrathin gels.
AB  - We have developed a simple and efficient technique for automated parallel loading
      of >/=200 lanes on a 30 cm-wide gel in automated DNA sequencing, using porous
      filter materials and an associated manual or robotic system. The samples are
      loaded onto the teeth of a comb made of the porous material. The comb, with
      samples, is inserted directly above the straight edge of the polymerized gel. The
      samples are driven from the comb into the gel by the applied electrical field. A
      particularly advantageous aspect of this method is the elimination of the thin
      gel walls separating the sample wells in the standard gel loading technique. The
      time for sample loading is significantly reduced to a few minutes. The loading
      technique is applicable to horizontal or vertical systems, with standard or
      ultrathin gels.

PMID- 9153327
TI  - Construction of multiple-epitope tag sequence by PCR for sensitive Western blot
      analysis.
AB  - Epitope tagging is a powerful technique to characterize a recombinantly expressed
      protein encoded by cDNA without the purification of the protein and the
      immunization of animals. In some cases, however, the expression of a tagged
      protein is too low to analyze by Western blot. We have developed a simple method
      to generate tandem repetitive nucleotide sequence by PCR, which allows us to
      label a protein of interest with a multiple-epitope tag. When five myc epitopes
      were attached to vaccinia virus protein CrmA, its signal was multiplied 5.8 times
      in Western blot analysis, compared with that of one epitope-tagged CrmA.

PMID- 9153329
TI  - Complementary strand analysis: a new approach for allelic separation in complex
      polyallelic genetic systems.
AB  - We describe a method, complementary strand analysis (CSA), for separating alleles
      potentially from any heterozygous genetic locus. Locus specific PCR is performed
      generating two allelic products. The antisense strands are isolated and
      hybridised with a sense reference strand to form a chimeric DNA duplex for each
      allele which is then separated by non-denaturing PAGE. We demonstrate the
      application of CSA for separation of highly polymorphic HLA-A, -B and -Cw alleles
      and characterisation of HLA identity in related bone marrow donors and patients.
      CSA is capable of resolving one nucleotide differences in a DNA fragment nearly
      as large as a kilobase in length.

PMID- 9153328
TI  - Direct identification of differentially expressed genes by cycle sequencing and
      cycle labelling using the differential display PCR primers.
AB  - Differential display PCR (DD-PCR) is an mRNA fingerprinting technique to identify
      differentially expressed genes by comparative display of arbitrarily amplified
      cDNA subsets. This attractively simple screening method was, however, followed by
      a labour intensive multistep identification procedure for DD-PCR products. In
      this report we demonstrate for the mouse mast cell protease 2 (MMCP-2) and the
      cytotoxic T-lymphocyte associated gene transcript CTLA-1 a streamlined approach
      by (i) direct cycle sequencing with the upstream differential display (DD)
      primer, followed by (ii) the PCR based generation of an antisense northern probe
      with the downstream anchor primer.

PMID- 9153330
TI  - Rational primer design greatly improves differential display-PCR (DD-PCR).
AB  - Since its conception in 1992, differential display PCR (DD-PCR) has attracted
      widespread interest. Theoretically an attractive cloning approach, it combines
      the comparative analysis of several samples with the sensitivity of PCR. Although
      a large number of studies embracing this technology have been initiated, few
      novel genes of interest have been identified, suggesting that the method has not
      realised its potential. The present report shows that by modifying primer design,
      sampling of differentially expressed genes can be greatly enhanced and relevant
      genes can be isolated. Using our modified conditions DD-PCR efficiently screens a
      wide range of gene expression levels, in which differences are represented on a
      linear scale.

PMID- 9153331
TI  - Efficient combination of large DNA in vitro: in gel site specific recombination
      (IGSSR) of PAC fragments containing alpha satellite DNA and the human HPRT gene
      locus.
AB  - In an attempt to combine a cloned genomic copy of a selectable gene with
      different cloned centromeric sequences to develop mammalian artificial
      chromosomes (MAC) we used site specific recombination mediated by purified Cre
      recombinase acting on the loxP sequence in PAC vector DNA. A new method was
      required to purify highly concentrated, virtually 100% intact PAC DNA which could
      be stored for a long period. Here we show the efficient linking of linearized
      PACs containing alpha satellite DNA from chromosomes X and 17 with sizes of 125
      and 140 kb, respectively, to a 95 kb restriction fragment derived from a 175 kb
      PAC containing the intact human HPRT gene locus.

PMID- 9153332
TI  - Contact dermatitis caused by triglycidyl isocyanurate.
AB  - A case of a 31-year-old color paint factory worker who developed contact
      dermatitis of the face and forearms on exposure to triglycidyl isocyanurate is
      reported. Patch testing showed a positive allergic reaction to only 5%
      triglycidyl isocyanurate in methyl ethyl ketone. A face mask that had not been
      regularly cleaned probably promoted the patient's sensitization by its occlusive
      effect.

PMID- 9153333
TI  - Allergy and topical irritation associated with transdermal testosterone
      administration: a comparison of scrotal and nonscrotal transdermal systems.
AB  - BACKGROUND: Topical effects are the most common adverse event for the scrotal and
      nonscrotal transdermal testosterone systems. OBJECTIVE: The study compared
      topical irritation rates for scrotal (Testoderm Testosterone Transdermal System;
      ALZA Corporation, Palo Alto, CA) and nonscrotal (Androderm Testosterone
      Transdermal System; SmithKline Beecham Pharmaceuticals, Philadelphia, PA)
      products. METHODS: This open-label, crossover study randomized 60 healthy, adult
      males to 14 days each of two treatments: one 40-cm2 scrotal system delivering
      approximately 4 mg testosterone over 24 hours, or two 37-cm2 nonscrotal systems
      worn on the back or upper outer arm, providing approximately 5 mg testosterone
      over 24 hours. Severity of topical effects was scored at system removal. RESULTS:
      Allergic contact dermatitis and spontaneous flaring of prior application sites
      occurred in 7 (12%) subjects using nonscrotal systems on Day 12; no confirmed
      cases of allergy to the scrotal system were observed (p < 0.001). For scrotal and
      nonscrotal systems respectively, moderately intense irritation was noted
      immediately after system removal in 5% and 32% of subjects (p < 0.001), and in 1%
      and 7% of systems applied (p < 0.001). CONCLUSION: Scrotal systems produced no
      confirmed contact allergy and less topical irritation than nonscrotal systems.
      The four subjects with contact allergy to nonscrotal systems used the scrotal
      system without a reaction, suggesting testosterone was not the allergen.

PMID- 9153334
TI  - Contact dermatitis to multiple exotic woods.
AB  - Occupational contact dermatitis to individual wood species from foreign
      countries, such as Asia, Africa, Central America, and South America, has been
      described. This report concerns the case of a domestic woodworker who developed
      allergic contact dermatitis shortly after beginning to work with multiple exotic
      woods. Patch testing with domestic and exotic wood fresh sawdust samples, 1% and
      10% in petrolatum, yielded strong positive reactions to six exotic woods:
      zericote, pao ferro, cocobolo, becote, macassar ebony, and padauk. Later testing
      confirmed sensitivity to the allergenic quinonoid constituents in pao ferro (R
      3,4-dimethoxydalbergione), cocobolo (obtusaquinone), and macassar ebony (macassar
      quinone).

PMID- 9153335
TI  - Airborne allergic contact dermatitis from pine dust.
AB  - BACKGROUND: Airborne contact dermatitis is a challenging entity that requires
      comprehensive patch testing and exposure review to diagnose accurately.
      OBJECTIVE: Four patients with airborne contact dermatitis and positive patch
      tests to colophony were evaluated. METHODS: Patch testing was performed on all
      patients using a modified European standard series plus additional applicable
      allergens. RESULTS: All patients had positive patch tests to colophony and
      exposure to pine dust. CONCLUSION: Patch testing is a critical element in the
      evaluation of patients presenting with an airborne pattern of contact dermatitis.

PMID- 9153338
TI  - (If the regulators don't get you) your competitors will.

PMID- 9153340
TI  - Sensitive skin: perceptions, evaluation, and treatment.
AB  - BACKGROUND: Patients with sensitive skin can present a challenge for
      dermatologists and cosmetic chemists alike. Knowledge of this common skin
      condition and appropriate dermatologic treatment, in combination with a rational
      approach to skin-care product selection, are important to patient well-being.
      OBJECTIVE: This report summarizes the subjective and objective findings in
      patients with sensitive skin while presenting a theory to explain disease
      physiology. Finally, a recommended treatment approach and formulation guidelines
      are presented. CONCLUSION: Sensitive skin possesses one or more of the following
      anatomic cutaneous changes: heightened neurosensory input, enhanced immune
      responsiveness, and/or diminished barrier function. Cosmetic and skin-care
      product formulation considerations for sensitive skin include products with a
      paucity of ingredients, absence of common sensitizers, minimum number of
      irritants, and absence of cutaneous sensory or vasodilatory stimulants.

PMID- 9153341
TI  - Workshop on irritant contact dermatitis.

PMID- 9153342
TI  - A new frequency based automatic sleep analysis - description of the healthy
      sleep.
AB  - A new system for complete automated sleep analysis has been developed
      (Somnoscript2000). Eighteen healthy young volunteers (ages 21-28 years, 9 females
      and 9 males) underwent a complete polysomnographic (PSG) registration. EEG from
      17 electrode positions was recorded simultaneously with the polygraphic
      parameters (CATEEM(R)). The characterization of the recorded bioelectrical
      signals is based on the spectral frequency analysis by Fast Fourier
      Transformation (FFT). A new sleep-staging algorithm was developed, which allows
      for an objective presentation of the sleep phenomena. This system is
      characterized by a high reproducibility of the individual polysomnographic data
      throughout the recording with no significant difference between different all
      night recordings of the subject. The sleep architecture shows considerable
      intersubject variability leading to differentiation of two main subpopulations:
      "good" and "poor sleepers".

PMID- 9153343
TI  - Mild rhabdomyolysis after high-dose trimethoprim-sulfamethoxazole in a patient
      with HIV infection.
AB  - Adverse drug reactions to trimethoprim-sulfamethoxazole (TMP/SMX) are common in
      HIV-positive patients. However, only one case of TMP/SMX-related rhabdomyolysis
      has been reported, so far. We report a 55-year old-man with asymptomatic
      rhabdomyolysis after oral high-dose TMP/SMX for suspected PCP. Laboratory changes
      settled after discontinuation of the drug.

PMID- 9153344
TI  - Iatrogenic spinal epidural abscesses: early diagnosis essential for good outcome.
AB  - Spinal epidural abscess usually arises by hematogenous, lymphatic or venous
      spread. The frequent use of invasive procedures at the spinal cord such as
      epidural injections to produce analgesia has led to an increased incidence of
      iatrogenic abscesses. We describe 8 patients who developed iatrogenic spinal
      epidural abscesses after paravertebral or intragluteal punctures respectively
      intravenous catheters to produce analgesia. Deep paravertebral or intragluteal
      injections were the cause of abscess formation in five, a contaminated
      intravenous line in two and a peridural catheter in one case. Pain of the
      affected vertebral column and malaise were the leading symptoms and
      Staphylococcus aureus was isolated in all cases. Diagnosis was made by means of
      magnetic resonance (n = 7) or Computed tomography (n = 1). Outcome was excellent
      with early therapy consisting of laminectomy and/or antibiotic treatment in the
      six patients treated within two days of appearance of symptoms. Invasive
      procedures at the spinal cord can lead to iatrogenic spinal epidural abscesses.
      Physicians dealing with deep punctures and catheter procedures should be aware of
      early symptoms and signs of an epidural abscess, since early diagnosis and
      specific therapy are the most important factors for a good outcome.

PMID- 9153345
TI  - Procalcitonin in acute malaria.
AB  - Procalcitonin, the precursor of calcitonin, is elevated in patients with sepsis
      and infection (base-line values <0.1 ng/ml). We determined PCT in 38 hospitalised
      patients with suspected malaria. All of them had signs of infection and had
      recently returned from Africa. Plasmodium vivax was proven in 15, Plasmodium
      falciparum in one and an infection with both species was found in another case (n
      = 17). PCT was determined on admission and the days thereafter. In one patient
      PCT was determined every 4 hours on the first day. The maxima of the PCT
      concentration on day 0 and 1 were 5.3 ng/ml with proven Malaria and 0.43 ng/ml
      without. At the following days we found a decrease to normal values (<0.5 ng/ml)
      which correlated with the general condition of the patient. At a cut-off point of
      2 ng/ml we found a sensitivity of 52%, positive predictive value of 74%,
      specificity of 86%, negative predictive value of 71%. procalcitonin, malaria

PMID- 9153346
TI  - Significant changes in thyroid hormone parameters after a four week recreation
      period at the North Sea without alterations of iodine intake.
AB  - Many studies have been carried out evaluating thyroid hormone parameters in
      patients suffering from various illnessess. However data on thyroid function
      after a recreation period are missing. Therefore we evaluated thyroid hormone
      parameters in 178 patients (mostly suffering from chronic obstructive lung
      disease) undergoing a four week recreation period in a health spa on the island
      Borkum at the North Sea. We observed a subtle, but significant increase in basal
      TSH concentrations from 1.20 mU/l (median) to 1.50 mU/l; (p<0. 001) and a fall in
      T4 values from 97.5 +/- 17.7 nmol/l (mean +/- SD) to 90.3 +/- 17.0 (p<0.001) and
      T3 from 2.21 +/- 0.33 nmol/l to 2.09 +/- 0.33 (p<0.001). However no increase in
      iodine intake occurred during the four weeks: median iodine excretion 61 microg
      iodine/g creatinine at the beginning vs 65 microg iodine/g creatinine at the end.
      IN CONCLUSION: a recreation period at the North Sea is associated with subtle but
      significant changes in thyroid hormone parameters. However no increase in iodine
      intake occurs during the four week observation period.

PMID- 9153348
TI  - Thyroid and adrenal function in HIV-infected outpatients.
AB  - We investigated parameters of thyroid and endocrine functions in 100 HIV-infected
      men who were grouped according to the CDC criteria. Progression of the disease
      was associated with a 44% increase in plasma TBG and a 15% increase in plasma
      CBG, while the T4/TBG ratio was decreased by 20%, plasma DHEAS was lowered by 30%
      and urinary aldosterone excretion fell by 70%. Plasma T4, T3 and TSH and urinary
      excretion of cortisol and catecholamines was not influenced by the disease. A
      weak, but significant negative correlation was found between plasma CBG and the
      body mass index of the patients. Significant positive correlations were observed
      between CD-4 cell count and the T4/TBG-ratio or plasma DHEAS levels. TBG was
      inversely correlated with CD-4 cell count and DHEAS. Thus, an increase in plasma
      TBG and a shift from adrenal androgen and mineralocorticoid steroid secretion
      towards cortisol secretion may be endocrine markers for progression of the
      disease in patients with HIV-infection.

PMID- 9153347
TI  - Fasting and postprandial disposition of R(-)- and S(+)-ibuprofen following oral
      administration of racemic drug in healthy individuals.
AB  - The effects of preceding food intake on the plasma concentrations of R(-)
      ibuprofen and the pharmacologically active enantiomer S(+)-ibuprofen were
      investigated in healthy subjects. A single oral dose of 400 mg racemic ibuprofen
      was administered either fasting or following a standardized meal. As compared to
      fasting administration postprandial drug intake resulted in a clear reduction of
      R(-) and S(+)- ibuprofen plasma concentrations mainly during the initial three
      hours. The ratio of S(+)/R(-)-ibuprofen postprandially was increased for Cmax and
      AUC o-tmax as well as for AUC o-infinity. These data are compatible with a meal
      induced enhancement of chiral inversion of R(-) to S(+)-ibuprofen. The
      significant reduction of plasma concentrations of ibuprofen mainly during the
      initial three hours suggests that the analgesic efficacy is diminished when the
      drug is taken after a meal. This may to a slight extent be compensated for by a
      small increase of the metabolic inversion of the R(-)-enantiomer into the active
      S(+)-form of the drug.

PMID- 9153350
TI  - A piece of my mind. He lifted his eyes.

PMID- 9153349
TI  - Diagnostic value of immunochemical fecal occult blood test for small colorectal
      neoplasms.
AB  - This study was designed to assess the diagnostic value of an immunochemical fecal
      occult blood test for small colorectal adenomas. In a screening program based
      comparative study, 60 colorectal adenomas under 1 cm (small polyp group), 60
      colorectal adenomas 1 cm or larger (large polyp group) and 60 colorectal cancers
      (cancer group) detected by occult blood screening, and 120 healthy controls
      (control group), served as subjects. Moreover, 50 small adenomas, 50 large
      adenomas and 50 cancers detected in out-patient clinics, and 100 controls, served
      as subjects of a hospital based comparative study. Each of these subjects was
      tested by an immunochemical occult blood with 3 consecutive days, after removal
      of these colorectal neoplasms in a screening program based study and before as
      well as after removal in a hospital based study, and the positivity rate of this
      test was evaluated among these four groups in the two comparative studies. The
      positivity rate in a screening program based study was 23% for small polyp group,
      8% for large polyp group, 5% for cancer group and 6% for control group,
      respectively. Significant difference was noted between small polyp and cancer as
      well as control groups (p <0.01), and between small polyp and large polyp groups
      (p <0.05). In a hospital based study, however, there was no significant
      difference in the positivity rate among four groups. These results suggest that
      high proportion of small polyps detected by fecal occult blood test screening may
      not be associated with bleeding from adenomas but probably from another
      gastrointestinal pathology.

PMID- 9153351
TI  - Helping city children control asthma.

PMID- 9153352
TI  - Physicians face new contradictions in HIV care.

PMID- 9153353
TI  - Coma-inducing drug GHB may be reclassified.

PMID- 9153354
TI  - From the Centers for Disease Control and Prevention. Targeted screening for
      childhood lead exposure in a low prevalence area--Salt Lake County, Utah, 1995
      1996.

PMID- 9153355
TI  - From the Centers for Disease Control and Prevention. AIDS rates.

PMID- 9153356
TI  - From the Centers for Disease Control and Prevention. Gamma hydroxy butyrate use-
      New York and Texas, 1995-1996.

PMID- 9153357
TI  - From the Centers for Disease Control and Prevention. Pregnancy-related behaviors
      among migrant farm workers--four states, 1989-1993.

PMID- 9153358
TI  - From the Centers for Disease Control and Prevention. Multidrug-resistant
      Salmonella serotype Typhimurium--United States, 1996.

PMID- 9153359
TI  - Estrogen replacement therapy: new options, continuing concerns.

PMID- 9153360
TI  - Estrogen replacement therapy: new options, continuing concerns.

PMID- 9153361
TI  - Major depressive disorder following miscarriage.

PMID- 9153362
TI  - Purchase of managed care: informed consumers or a distorted market?

PMID- 9153363
TI  - Have quality improvement efforts decreased mortality rates following cardiac
      surgery?

PMID- 9153364
TI  - Therapeutic effect of combination antiretroviral therapy on cytomegalovirus
      retinitis.

PMID- 9153365
TI  - Effects of mental stress on myocardial ischemia during daily life.
AB  - OBJECTIVE: To determine the relative risk of myocardial ischemia triggered by
      specific emotions during daily life. DESIGN AND SETTING: Relative risk was
      calculated by the recently developed case-crossover method, in which the
      frequency of a presumed trigger during nonischemic, or control, hours is compared
      with the trigger's frequency during ischemic, or case, hours. Outpatients at Duke
      University Medical Center, Durham, NC, underwent 48 hours of ambulatory
      electrocardiographic (ECG) monitoring with concurrent self-report measures of
      activities and emotions. Occurrences of negative emotions in the hour before the
      onset of myocardial ischemia were compared with their usual frequency based on
      all hours in which ischemia did not occur. SUBJECTS: From a sample of 132
      patients with coronary artery disease and recent evidence of exercise-induced
      ischemia who underwent 48 hours of ambulatory ECG monitoring, 58 patients
      exhibited ambulatory ischemia and were included in the analysis. OUTCOME
      MEASURES: Myocardial ischemia during 48-hour ECG monitoring was defined as
      horizontal or downsloping ST-segment depression of 1 mm (0.1 mV) or more for 1
      minute or longer compared with resting baseline. The ECG data were cross
      tabulated with subjects' concurrent diary ratings of 3 negative emotions-tension,
      sadness, and frustration-and 2 positive emotions-happiness and feeling in contro
      on a 5-point scale of intensity. RESULTS: The unadjusted relative risk of
      occurrence of myocardial ischemia in the hour following high levels of negative
      emotions was 3.0 (95% confidence interval [CI], 1.5-5.9; P<.01) for tension, 2.9
      (95% CI, 1.0-8.0; P<.05) for sadness, and 2.6 (95% CI, 1.3-5.1; P<.01) for
      frustration. The corresponding risk ratios adjusted for physical activity and
      time of day were 2.2 (95% CI, 1.1 -4.5; P<.05) for tension, 2.2 (95% CI, 0.7-6.4;
      P=.16) for sadness, and 2.2 (95% CI, 1.1-4.3; P<.05) for frustration.
      CONCLUSIONS: Mental stress during daily life, including reported feelings of
      tension, frustration, and sadness, can more than double the risk of myocardial
      ischemia in the subsequent hour. The clinical significance of mental stress
      induced ischemia during daily life needs to be further evaluated.

PMID- 9153366
TI  - A randomized trial comparing octylcyanoacrylate tissue adhesive and sutures in
      the management of lacerations.
AB  - OBJECTIVE: To assess the effectiveness of a new tissue adhesive for laceration
      closure. DESIGN: A prospective, randomized controlled trial. SETTING: An adult
      teaching hospital. PARTICIPANTS: One hundred thirty patients with 136 lacerations
      who consented to enrollment during a 5-month period. The lacerations included all
      eligible nonmucosal facial lacerations, as well as selected extremity and torso
      lacerations (not on hands, feet, or joints). One hundred six lacerations were
      available for early follow-up, and 98 were available for 3-month evaluation.
      INTERVENTIONS: Lacerations were randomly allocated to have skin closure with
      octylcyanoacrylate adhesive or monofilament suture. MAIN OUTCOME MEASURE: A 3
      month photograph of the wound was assigned a cosmesis score on a previously
      validated 100-mm visual analog cosmesis scale by a plastic surgeon who was
      unaware of the method of wound closure. RESULTS: There were no differences in the
      mean visual analog cosmesis scores (67 mm for octylcyanoacrylate vs 68 mm for
      sutures; P=.65). Similarly, there was no difference in the percentage of early
      (80% vs 82%; P=.80) or late (72% vs 75%; P=.74) optimal wound evaluation scores.
      The tissue adhesive was a faster method of wound repair (3.6 vs 12.4 minutes;
      P<.001) as well as being less painful (visual analog pain scores, 7.2 vs 18.0 mm;
      P<.001). CONCLUSIONS: Octylcyanoacrylate tissue adhesive effectively closes
      selected lacerations. This relatively painless and fast method of wound repair
      can replace the need for suturing several million lacerations each year.

PMID- 9153367
TI  - p55 Tumor necrosis factor receptor fusion protein in the treatment of patients
      with severe sepsis and septic shock. A randomized controlled multicenter trial.
      Ro 45-2081 Study Group.
AB  - OBJECTIVE: To evaluate the safety and efficacy of p55 tumor necrosis factor
      receptor fusion protein, a recombinant chimeric protein of human p55 (type I)
      tumor necrosis factor receptor (CD120a) extracellular domain and IgG1 sequences
      (referred to as p55-IgG), in the treatment of patients with severe sepsis or
      septic shock. DESIGN: Randomized, prospective, multicenter, double-blind, placebo
      controlled clinical trial. SETTING: Forty-four community and university
      affiliated hospitals in the United States and Europe. PATIENTS: There were 498
      patients enrolled in this clinical trial. INTERVENTION: Patients prospectively
      stratified within each site into refractory shock or severe sepsis groups were
      randomized to receive a single infusion of p55-IgG, 0.083 mg/kg, 0.042 mg/kg, or
      0.008 mg/kg, or placebo. Patients received standard aggressive medical/surgical
      care during the 28-day postinfusion period. OUTCOME MEASURE: Twenty-eight-day all
      cause mortality. RESULTS: The distribution of variables describing demographics,
      organ system dysfunction or failure, infecting microorganisms, predicted
      mortality, plasma interleukin 6 levels, and plasma tumor necrosis factor alpha
      (TNF-alpha) levels were similar among patients in the p55-IgG and placebo
      treatment arms. A planned interim analysis was performed after 201 patients were
      enrolled. Because a statistically nonsignificant trend toward increased mortality
      was present in patients who had received 0.008 mg/kg, this treatment arm was
      discontinued, and the study continued with 3 arms. Among all infused patients,
      there was a statistically nonsignificant trend toward reduced 28-day all-cause
      mortality in those who received p55-IgG compared with placebo-treated patients
      (5% reduction, 0.042 mg/kg vs placebo; 15% reduction, 0.083 mg/kg vs placebo;
      P=.30). However, in patients with severe sepsis and early septic shock (n=247),
      therapy with p55-IgG, 0.083 mg/kg, was associated with a 36% reduction in 28-day
      all-cause mortality compared with placebo (P=.07): 20 (23%) of 87 patients died
      among those treated with p55-IgG, 0.083 mg/kg; 30 (37%) of 82 among those treated
      with p55-IgG, 0.042 mg/kg; and 28 (36%) of 78 in the placebo group. A
      prospectively planned logistic regression analysis to assess treatment effect on
      28-day all-cause mortality by means of predicted mortality and serum interleukin
      6 levels as continuous covariates demonstrated a significant improvement in
      outcome for the patients with severe sepsis treated with p55-IgG, 0.083 mg/kg,
      compared with placebo (P=.01). Serious adverse events, including death and the
      development of new organ system dysfunction, were reported in 65% of patients
      infused with placebo, with no increased frequency (56%) present in the 2 p55-IgG
      treatment arms. There were no reports of immediate hypersensitivity reactions
      caused by p55-IgG. CONCLUSIONS: In this dose-finding study, there was no decrease
      in mortality between placebo and p55-IgG in all infused patients. In the
      prospectively defined population of patients with severe sepsis who received p55
      IgG, 0.083 mg/kg, there was a trend toward reduced mortality at day 28 that
      became significant when predicted mortality and plasma interleukin 6 levels were
      included in a logistic regression analysis.

PMID- 9153368
TI  - A prospective study of body mass index, weight change, and risk of stroke in
      women.
AB  - OBJECTIVE: To examine the associations of body mass index (BMI) and weight change
      with risk of stroke in women. SETTING AND DESIGN: Prospective cohort study among
      US female registered nurses participating in the Nurses' Health Study.
      PARTICIPANTS: A total of 116759 women aged 30 to 55 years in 1976 who were free
      from diagnosed coronary heart disease, stroke, and cancer. MAIN OUTCOME MEASURE:
      Incidence of ischemic stroke, hemorrhagic stroke (subarachnoid or
      intraparenchymal hemorrhage), and total stroke. RESULTS: During 16 years of
      follow-up, 866 total strokes (including 403 ischemic strokes and 269 hemorrhagic
      strokes) were documented. In multivariate analyses adjusted for age, smoking,
      postmenopausal hormone use, and menopausal status, women with increased BMI (> or
      =27 kg/m2) had significantly increased risk of ischemic stroke, with relative
      risks (RRs) of 1.75 (95% confidence interval [CI], 1.17-2.59) for BMI of 27 to
      28.9 kg/m2; 1.90 (95% CI, 1.28-2.82) for BMI of 29 to 31.9 kg/m2; and 2.37 (95%
      CI, 1.60-3.50) for BMI of 32 kg/m2 or more (P for trend<.001), as compared with
      those with a BMI of less than 21 kg/m2. For hemorrhagic stroke there was a
      nonsignificant inverse relation between obesity and hemorrhagic stroke, with the
      highest risk among women in the leanest BMI category (P for trend=.20). For total
      stroke the RRs were somewhat attenuated compared with those for ischemic stroke
      but remained elevated for women with higher BMI (P for trend<.001). In
      multivariate analyses that also adjusted for BMI at age 18 years, weight gain
      from age 18 years until 1976 was associated with an RR for ischemic stroke of
      1.69 (95% CI, 1.26-2.29) for a gain of 11 to 19.9 kg and 2.52 (95% CI, 1.80-3.52)
      for a gain of 20 kg or more (P for trend<.001), as compared with women who
      maintained stable weight (loss or gain <5 kg). Although weight change was not
      related to risk of hemorrhagic stroke (P for trend=.20), a direct relationship
      was observed between weight gain and total stroke risk (P for trend<.001).
      CONCLUSIONS: These prospective data indicate that both obesity and weight gain in
      women are important risk factors for ischemic and total stroke but not
      hemorrhagic stroke. The relationship between obesity and total stroke depends on
      the distribution of stroke subtypes in the population.

PMID- 9153369
TI  - Dengue fever in US military personnel in Haiti.
AB  - OBJECTIVE: To describe clinical manifestations and public health implications of
      an outbreak of dengue fever (DF) during Operation Uphold Democracy, Haiti, 1994.
      DESIGN: Consecutive sample. SETTING: Military combat support hospital, Port-au
      Prince, Haiti. PATIENTS: A total of 101 US military personnel with acute febrile
      illnesses. INTERVENTIONS: A disease surveillance team collected clinical and
      epidemiologic data from US military clinics throughout Haiti. Febrile patients
      admitted to the combat support hospital were evaluated with standardized clinical
      and laboratory procedures. The surveillance team followed patients daily. MAIN
      OUTCOME MEASURES: Arbovirus isolation and specific antibody determination and
      symptoms and physical findings. RESULTS: Febrile illnesses accounted for 103
      (25%) of the 406 combat support hospital admissions during the first 6 weeks of
      deployment. All patients with febrile illness recovered. A total of 30 patients
      had DF; no patient had evidence of infection with malaria. Dengue virus serotypes
      1, 2, and 4 were isolated from 22 patients, and 8 patients developed IgM antibody
      to dengue virus. Patients with DF could not be distinguished from other febrile
      patients on clinical grounds alone. No arboviruses other than dengue were
      identified. CONCLUSIONS: Active surveillance, with clinical and laboratory
      evaluation directed by an epidemiologic team, led to the timely recognition of an
      outbreak of febrile illness among US troops in Haiti. Viral isolation and
      serological studies were essential in confirming DF. During the surveillance
      period, DF accounted for at least 30% of the febrile illnesses among hospitalized
      US troops. Dengue fever is a significant threat to military personnel and
      civilian travelers in Haiti and has the potential for introduction to and
      transmission in the United States.

PMID- 9153370
TI  - Antiphospholipid antibody. Babies, blood clots, biology.

PMID- 9153371
TI  - Users' guides to the medical literature. XIII. How to use an article on economic
      analysis of clinical practice. A. Are the results of the study valid? Evidence
      Based Medicine Working Group.

PMID- 9153372
TI  - Mental stress during daily life triggers myocardial ischemia.

PMID- 9153373
TI  - Cyanoacrylate tissue adhesives. An advance in wound care.

PMID- 9153374
TI  - Retraining physicians for primary care. A study of physician perspectives and
      program development.
AB  - OBJECTIVE: To determine the number and kinds of programs that medical schools and
      managed care organizations offer or plan to offer to retrain physician
      specialists to practice primary care medicine and to discover physicians'
      attitudes toward such retraining. DESIGN: A survey was mailed in 1994 to all 126
      medical schools and the 19 largest US managed care organizations to collect
      detailed information about existing and potential retraining programs.
      Physicians' attitudes toward retraining were elicited from participants in 3
      geographically diverse focus groups. Selected specialists were polled through the
      national survey of the American Medical Association's Socioeconomic Monitoring
      System to ascertain the demand for retraining. RESULTS: The majority of
      institutions contacted perceived a need for retraining, but few programs had been
      established. Programs being "considered" varied widely in duration, class size,
      target audience, accreditation, and projected training settings. Although
      unenthusiastic about retraining, physicians preferred programs that would expand
      their patient base, maintain the practice population, be inexpensive and close to
      home, and provide hands-on training in the eventual practice environment.
      Physicians also preferred a goal-oriented, part-time retraining program in a
      large group practice or managed care setting that would allow them to practice
      their specialty while retraining. Few planned or existing programs incorporate
      many of these features. The most likely candidates for retraining are
      subspecialty physicians who currently provide some primary care and are employed
      by a medical plan. CONCLUSIONS: Despite efforts by those who perceive that a need
      for more generalist physicians is stimulating interest in retraining specialists
      and subspecialists to provide primary medical care, physician interest and
      program availability remain low, and programs under development are not being
      designed to attract those who may seek retraining. This situation is probably
      fortuitous, because changed perceptions about the adequacy of the generalist
      physician workforce since the beginning of this study have diminished the call
      for retraining.

PMID- 9153375
TI  - US panel to back longer cloning ban, ducks thornier questions.

PMID- 9153376
TI  - Roslin patents come under the spotlight.

PMID- 9153377
TI  - France is urged to loosen ban on embryo research.

PMID- 9153378
TI  - Truce likely in battle over 'DNA-chip' patent rights.

PMID- 9153379
TI  - Hughes confirms its faith in excellence.

PMID- 9153380
TI  - Placebo use defended in Third World studies.

PMID- 9153381
TI  - TB still a global killer.

PMID- 9153382
TI  - Muscle structure. Molecular bungees.

PMID- 9153383
TI  - Jupiter's moons. Virgin Callisto.

PMID- 9153384
TI  - Synthetic chemistry. Cancer drugs better than taxol?

PMID- 9153385
TI  - RNA editing. Message change for a fat controller.

PMID- 9153386
TI  - Poultry virus infection in Antarctic penguins.

PMID- 9153387
TI  - Infant leukaemia after the Chernobyl accident.

PMID- 9153388
TI  - Animal mitochondrial DNA recombination.

PMID- 9153389
TI  - Gravitational evidence for an undifferentiated Callisto.
AB  - Before the arrival of the Galileo spacecraft at Jupiter, models for the interior
      structure of the four galilean satellites--Io, Europa, Ganymede and Callisto
      ranged from uniform mixtures of rock and ice (that is, undifferentiated objects)
      or rocky cores surrounded by a mantle of water ice. Now it appears that Io has a
      large metallic core and that Ganymede is strongly differentiated, most probably
      into a three-layer structure consisting of a metallic core, a silicate mantle and
      a deep outer layer of ice. Direct information on the interior structure of
      Callisto determined from previous spacecraft fly-bys was essentially limited to
      an estimate of the mean density being intermediate between pure ice and pure
      rock. Here we report measurements of Callisto's gravitational field which reveal
      that, in contrast to Io and Ganymede, this galilean satellite is most probably a
      homogeneous object consisting of a solar mixture of 40% compressed ice and 60%
      rock (including iron and iron sulphide). Callisto's undifferentiated state is
      consistent with the apparent lack of an intrinsic magnetic field, and indicates
      that the outermost galilean satellite has not experienced a heating phase
      sufficiently high to separate its rock and metal components from the lighter
      ices.

PMID- 9153390
TI  - Synthesis of epothilones A and B in solid and solution phase.
AB  - Epothilones A and B, two compounds that have been recently isolated from
      myxobacterium Sorangium cellulosum strain 90, have generated intense interest
      among chemists, biologists and clinicians owing to the structural complexity,
      unusual mechanism of interaction with microtubules and anticancer potential of
      these molecules. Like taxol, they exhibit cytotoxicity against tumour cells by
      inducing microtubule assembly and stabilization, even in taxol-resistant cell
      lines. Following the structural elucidation of these molecules by X-ray
      crystallography in 1996, several syntheses of epothilones A and B have been
      reported, indicative of the potential importance of these molecules in the cancer
      field. Here we report the first solid-phase synthesis of epothilone A, the total
      synthesis of epothilone B, and the generation of a small epothilone library. The
      solid-phase synthesis applied here to epothilone A could open up new
      possibilities in natural-product synthesis and, together with solution-phase
      synthesis of other epothilones, paves the way for the generation of large
      combinatorial libraries of these important molecules for biological screening.

PMID- 9153391
TI  - Synaptic plasticity in a cerebellum-like structure depends on temporal order.
AB  - Cerebellum-like structures in fish appear to act as adaptive sensory processors,
      in which learned predictions about sensory input are generated and subtracted
      from actual sensory input, allowing unpredicted inputs to stand out. Pairing
      sensory input with centrally originating predictive signals, such as corollary
      discharge signals linked to motor commands, results in neural responses to the
      predictive signals alone that are 'negative images' of the previously paired
      sensory responses. Adding these 'negative images' to actual sensory inputs
      minimizes the neural response to predictable sensory features. At the cellular
      level, sensory input is relayed to the basal region of Purkinje-like cells,
      whereas predictive signals are relayed by parallel fibres to the apical dendrites
      of the same cells. The generation of negative images could be explained by
      plasticity at parallel fibre synapses. We show here that such plasticity exists
      in the electrosensory lobe of mormyrid electric fish and that it has the
      necessary properties for such a model: it is reversible, anti-hebbian (excitatory
      postsynaptic potentials (EPSPs) are depressed after pairing with a postsynaptic
      spike) and tightly dependent on the sequence of pre- and postsynaptic events,
      with depression occurring only if the postsynaptic spike follows EPSP onset
      within 60 ms.

PMID- 9153392
TI  - Dynamics of orientation tuning in macaque primary visual cortex.
AB  - Orientation tuning of neurons is one of the chief emergent characteristics of the
      primary visual cortex, V1. Neurons of the lateral geniculate nucleus, which
      comprise the thalamic input to V1, are not orientation-tuned, but the majority of
      V1 neurons are quite selective. How orientation tuning arises within V1 is still
      controversial. To study this problem, we measured how the orientation tuning of
      neurons evolves with time using a new method: reverse correlation in the
      orientation domain. Orientation tuning develops after a delay of 30-45
      milliseconds and persists for 40-85 ms. Neurons in layers 4C alpha or 4C beta,
      which receive direct input from the thalamus, show a single orientation
      preference which remains unchanged throughout the response period. In contrast,
      the preferred orientations of output layer neurons (in layers 2, 3, 4B, 5 or 6)
      usually change with time, and in many cases the orientation tuning may have more
      than one peak. This difference in dynamics is accompanied by a change in the
      sharpness of orientation tuning; cells in the input layers are more broadly tuned
      than cells in the output layers. Many of these observed properties of output
      layer neurons cannot be explained by simple feedforward models, whereas they
      arise naturally in feedback networks. Our results indicate that V1 is more than a
      bank of static oriented filters; the dynamics of output layer cells appear to be
      shaped by intracortical feedback.

PMID- 9153393
TI  - Presenilin 1 is required for Notch1 and DII1 expression in the paraxial mesoderm.
AB  - Approximately 10% of cases of Alzheimer's disease are familial and associated
      with autosomal dominant inheritance of mutations in genes encoding the amyloid
      precursor protein, presenilin 1 (PS1) and presenilin 2 (PS2). Mutations in PS1
      are linked to about 25% of cases of early-onset familial Alzheimer's disease.
      PS1, which is endoproteolytically processed in vivo, is a multipass transmembrane
      protein and is a functional homologue of SEL-12, a Caenorhabditis elegans protein
      that facilitates signalling mediated by the Notch/LIN-12 family of receptors. To
      examine potential roles for PS1 in facilitating Notch-mediated signalling during
      mammalian embryogenesis, we generated mice with targeted disruptions of PS1
      alleles (PS1-/- mice). PS1-/- embryos exhibited abnormal patterning of the axial
      skeleton and spinal ganglia, phenotypes traced to defects in somite segmentation
      and differentiation. Moreover, expression of mRNA encoding Notch1 and Dll1 (delta
      like gene 1), a vertebrate Notch ligand, is markedly reduced in the presomitic
      mesoderm of PS1-/- embryos compared to controls. Hence, PS1 is required for the
      spatiotemporal expression of Notch1 and Dll1, which are essential for somite
      segmentation and maintenance of somite borders.

PMID- 9153394
TI  - The role of RhoA in tissue polarity and Frizzled signalling.
AB  - The tissue polarity genes of Drosophila are required for correct establishment of
      planar polarity in epidermal structures, which in the eye is shown in the mirror
      image symmetric arrangement of ommatidia relative to the dorsoventral midline.
      Mutations in the genes frizzled (fz), dishevelled (dsh) and prickle-spiny-legs
      (pk-sple) result in the loss of this mirror-image symmetry. fz encodes a
      serpentine receptor-like transmembrane protein required for reception and
      transmission of a polarity signal. Little else is known of the signalling
      pathway(s) involved other than that Dsh acts downstream of Fz. We have identified
      mutations in the Drosophila homologue of RhoA p21 GTPase, and by analysis of
      their phenotype show that RhoA is required for the generation of tissue polarity.
      Genetic interactions indicate a role for RhoA in signalling mediated by Fz and
      Dsh, and furthermore suggest that JNK/SAPK-like kinases are involved. These data
      are consistent with a Fz/RhoA signalling cascade analogous to the yeast pheromone
      signalling pathway and that proposed for activation of the serum response factor
      (SRF) in vertebrate cells.

PMID- 9153395
TI  - Mdm2 promotes the rapid degradation of p53.
AB  - The p53 tumour-suppressor protein exerts antiproliferative effects, including
      growth arrest and apoptosis, in response to various types of stress. The activity
      of p53 is abrogated by mutations that occur frequently in tumours, as well as by
      several viral and cellular proteins. The Mdm2 oncoprotein is a potent inhibitor
      of p53. Mdm2 binds the transcriptional activation domain of p53 and blocks its
      ability to regulate target genes and to exert antiproliferative effects. On the
      other hand, p53 activates the expression of the mdm2 gene in an autoregulatory
      feedback loop. The interval between p53 activation and consequent Mdm2
      accumulation defines a time window during which p53 exerts its effects. We now
      report that Mdm2 also promotes the rapid degradation of p53 under conditions in
      which p53 is otherwise stabilized. This effect of Mdm2 requires binding of p53;
      moreover, a small domain of p53, encompassing the Mdm2-binding site, confers Mdm2
      dependent detstabilization upon heterologous proteins. Raised amounts of Mdm2
      strongly repress mutant p53 accumulation in tumour-derived cells. During recovery
      from DNA damage, maximal Mdm2 induction coincides with rapid p53 loss. We propose
      that the Mdm2-promoted degradation of p53 provides a new mechanism to ensure
      effective termination of the p53 signal.

PMID- 9153396
TI  - Regulation of p53 stability by Mdm2.
AB  - The tumour-suppressor p53 is a short-lived protein that is maintained at low,
      often undetectable, levels in normal cells. Stabilization of the protein in
      response to an activating signal, such as DNA damage, results in a rapid rise in
      p53 levels and subsequent inhibition of cell growth. Tight regulation of p53
      function is critical for normal cell growth and development, and one mechanism by
      which p53 function is controlled is through interaction with the Mdm2 protein.
      Mdm2 inhibits p53 cell-cycle arrest and apoptic functions and we show here that
      interaction with Mdm2 can also result in a large reduction in p53 protein levels
      through enhanced proteasome-dependent degradation. Endogenous levels of Mdm2 are
      sufficient to regulate p53 stability, and overexpression of Mdm2 can reduce the
      amount of endogenous p53. Because mdm2 is transcriptionally activated by p53,
      this degradative pathway may contribute to the maintenance of low p53
      concentrations in normal cells. Furthermore, mechanisms regulating the Mdm2
      induced degradation of p53 may play a role in controlling the extent and duration
      of the p53 response.

PMID- 9153397
TI  - Regulation of serotonin-2C receptor G-protein coupling by RNA editing.
AB  - The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) elicits a wide array
      of physiological effects by binding to several receptor subtypes. The 5-HT2
      family of receptors belongs to a large group of seven-transmembrane-spanning G
      protein-coupled receptors and includes three receptor subtypes (5-HT2A, 5-HT(2B)
      and 5-HT(2C)) which are linked to phospholipase C, promoting the hydrolysis of
      membrane phospholipids and a subsequent increase in the intracellular levels of
      inositol phosphates and diacylglycerol. Here we show that transcripts encoding
      the 2C subtype of serotonin receptor (5-HT(2C)R) undergo RNA editing events in
      which genomically encoded adenosine residues are converted to inosines by the
      action of double-stranded RNA adenosine deaminase(s). Sequence analysis of
      complementary DNA isolates from dissected brain regions have indicated the tissue
      specific expression of seven major 5-HT(2C) receptor isoforms encoded by eleven
      distinct RNA species. Editing of 5-HT(2C)R messenger RNAs alters the amino-acid
      coding potential of the predicted second intracellular loop of the receptor and
      can lead to a 10-15-fold reduction in the efficacy of the interaction between
      receptors and their G proteins. These observations indicate that RNA editing is a
      new mechanism for regulating serotonergic signal transduction and suggest that
      this post-transcriptional modification may be critical for modulating the
      different cellular functions that are mediated by other members of the G-protein
      coupled receptor superfamily.

PMID- 9153398
TI  - Elasticity and unfolding of single molecules of the giant muscle protein titin.
AB  - The giant muscle protein titin, also called connectin, is responsible for the
      elasticity of relaxed striated muscle, as well as acting as the molecular
      scaffold for thick-filament formation. The titin molecule consists largely of
      tandem domains of the immunoglobulin and fibronectin-III types, together with
      specialized binding regions and a putative elastic region, the PEVK domain. We
      have done mechanical experiments on single molecules of titin to determine their
      visco-elastic properties, using an optical-tweezers technique. On a fast (0.1s)
      timescale titin is elastic and force-extension data can be fitted with standard
      random-coil polymer models, showing that there are two main sources of
      elasticity: one deriving from the entropy of straightening the molecule; the
      other consistent with extension of the polypeptide chain in the PEVK region. On a
      slower timescale and above a certain force threshold, the molecule displays
      stress-relaxation, which occurs in rapid steps of a few piconewtons,
      corresponding to yielding of internal structures by about 20 nm. This stress
      relaxation probably derives from unfolding of immunoglobulin and fibronectin
      domains.

PMID- 9153399
TI  - Crystal structure of ICAM-2 reveals a distinctive integrin recognition surface.
AB  - Recognition by integrin proteins on the cell surface regulates the adhesive
      interactions between cells and their surroundings. The structure of the 'I'
      domain that is found in some but not all integrins, has been determined. However,
      the only integrin ligands for which structures are known, namely fibronectin and
      VCAM-1, are recognized by integrins that lack I domains. The intercellular
      adhesion molecules ICAM-1, 2 and 3 are, like VCAM-1, members of the
      immunoglobulin superfamily (IgSF), but they are recognized by an I domain
      containing integrin, lymphocyte-function-associated antigen 1 (LFA-1, or
      CD11a/CD18). Here we present the crystal structure of the extracellular region of
      ICAM-2. The glutamic acid residue at position 37 is critical for LFA-1 binding
      and is proposed to coordinate the Mg2+ ion in the I domain; this Glu 37 is
      surrounded by a relatively flat recognition surface and lies in a beta-strand,
      whereas the critical aspartic acid residue in VCAM-1 and fibronectin lie in
      protruding loops. This finding suggests that there are differences in the
      architecture of recognition sites between integrins that contain or lack I
      domains. A bend between domains 1 and 2 of ICAM-2 and a tripod-like arrangement
      of N-linked glycans in the membrane-proximal region of domain 2 may be important
      for presenting the recognition surface to LFA-1. A model of ICAM-1 based on the
      ICAM-2 structure provides a framework for understanding its recognition by
      pathogens.

PMID- 9153400
TI  - Potent bifunctional anticoagulants: Kunitz domain-tissue factor fusion proteins.
AB  - A strategy to design potent antagonists of human coagulation factor VIIa (FVIIa)
      by linking two proteins that independently inhibit activity and bind at separate,
      nonoverlapping sites is presented. A bifunctional inhibitor (KDTF5), comprising a
      Kunitz-type domain engineered to inhibit the FVIIa active site and a soluble
      tissue factor (TF) variant that is defective as a cofactor for factor X (FX)
      activation, was developed from structure-based modeling of a ternary FVIIa-Kunitz
      domain-TF complex. KDTF5 inhibited FVIIa-dependent FX activation with a Ki* of
      235 +/- 45 pM, a 193-fold and 398-fold increase in potency compared to the TF
      variant and Kunitz domain individually. Similarly, KDTF5 was a more potent
      anticoagulant in vitro compared to either inhibitory domain alone. The results
      demonstrate the harnessing of a macromolecular chelate effect by fusing two
      inhibitory ligands that bind a target at spatially distinct sites.

PMID- 9153401
TI  - Urea and thermal equilibrium denaturation studies on the dimerization domain of
      Escherichia coli Trp repressor.
AB  - The urea-induced equilibrium unfolding of the Escherichia coli Trp repressor (TR)
      is a two-state process, involving the native dimeric and unfolded monomeric
      species. Kinetic studies, however, reveal the presence of transient intermediates
      that appear only during the folding of the 107-residue protein [Gittelman, M. G.,
      & Matthews, C. R. (1990) Biochemistry 29, 7011-7020]. In order to gain insight
      into the complex kinetic folding mechanism, the sequence of TR was reduced to the
      amino-terminal 66 residues, corresponding to the dimerization domain. Two
      polypeptides, 2-66 and NHis-7-66, were shown to be dimeric at 25 degrees C by
      size exclusion chromatography and to retain native-like spectroscopic features as
      evidenced by near- and far-UV circular dichroism and fluorescence spectroscopy.
      The equilibrium properties of the urea-induced folding of these core fragments
      were examined by intrinsic tryptophan fluorescence and circular dichroism and
      found to be well described by a two-state model. At 25 degrees C, the stabilities
      of both fragments are 14 kcal mol(-1), as compared to the 24 kcal mol(-1)
      observed for full-length TR. In contrast, the thermal denaturation of [2-66]2 and
      full-length TR are three-state processes; the midpoint of the transition
      monitored by absorbance at 292 nm precedes that monitored by circular dichroism
      at 222 nm. Global analysis of the thermal data as a function of monomer
      concentration suggests that both the full-length and [2-66]2 TR variants unfold
      via a dimeric intermediate. Taken together, these results demonstrate that the [2
      66]2 fragment constitutes a well-structured, independently folding subdomain of
      TR that may be useful in elucidating the properties of the transient
      intermediates observed in the folding of the full-length protein. The dimeric
      intermediate observed in the thermal denaturation of [2-66]2 suggests that it may
      be possible to further reduce the core sequence while maintaining the ability to
      dimerize.

PMID- 9153402
TI  - Limited proteolysis and X-ray crystallography reveal the origin of substrate
      specificity and of the rate-limiting product release during oxidation of D-amino
      acids catalyzed by mammalian D-amino acid oxidase.
AB  - Limited proteolysis of D-amino acid oxidase holoenzyme with trypsin cleaves the
      protein at Arg 221 and near the C-terminus, producing stable 25, 13.4, and 2 kDa
      polypeptides [Torri-Tarelli, G., Vanoni, M. A., Negri, A., & Curti, B. (1990) J.
      Biol. Chem. 265, 21242-21246]. The 25 and 13.4 kDa polypeptides remain associated
      to form a nicked D-amino acid oxidase species. This nicked protein form maintains
      the ability to bind FAD, but exhibits altered catalytic efficiency toward the
      oxidation of various D-amino acids when compared to native DAAO. Changes in
      substrate specificity were first monitored by measuring the activity in the
      presence of different amino acid substrates at various times during proteolysis.
      Three amino acid substrates were then selected for further analysis of the
      properties of the nicked D-amino acid oxidase species produced by limited tryptic
      proteolysis: D-serine, D-arginine, and D-alanine. The three D-amino acids
      represented limiting cases of the observed changes of enzyme activity on nicking:
      loss of activity, increase of activity, and minor activity changes, respectively.
      D-serine was found to be no longer a substrate of D-amino acid oxidase. D
      arginine exhibited a 2.5-fold increased apparent maximum velocity although its Km
      value increased 2-fold with the nicked enzyme in comparison to the native
      species. D-alanine was oxidized 1.5-fold faster by the nicked D-amino acid
      oxidase at infinite substrate concentration, and its Km value increased
      approximately 4-fold. The Kd for benzoate, which was determined kinetically with
      D-alanine as the enzyme substrate, increased 17-fold in the nicked species.
      Primary deuterium kinetic isotope effects on V and V/K during the oxidation of D
      alanine were also measured. (D)V/K increased from 1.4 +/- 0.2 to 1.8 +/- 0.3 on
      nicking, while (D)V increased from 1.04 +/- 0.1 to 2.53 +/- 0.5. All the observed
      changes of the values of the kinetic parameters and of the observed isotope
      effects are consistent with the hypothesis that nicking of D-amino acid oxidase
      at position 221 decreases the strength of binding of both substrates and products
      to the enzyme active site. The information obtained by limited tryptic
      proteolysis nicely complements that gathered from the analysis of the three
      dimensional structure of D-amino acid oxidase in complex with benzoate, which was
      recently determined [Mattevi, A., Vanoni, M. A., Todone, F., Rizzi, M.,
      Teplyakov, A., Coda, A., Bolognesi, M., & Curti, B. (1996) Proc. Natl. Acad. Sci.
      U.S.A. 93, 7496-7501]. Arginine 221 is part of the 216-228 loop that covers the
      active site and contributes residues to substrate binding and catalysis. The
      limited proteolysis data support the hypothesis that this loop acts as a lid on
      the active site and controls both substrate specificity and the rate of turnover
      of D-amino acid oxidase.

PMID- 9153403
TI  - Structural mechanisms of bile salt-induced growth of small unilamellar
      cholesterol-lecithin vesicles.
AB  - The liver secretes cholesterol and lecithin in the form of mixed vesicles during
      the formation of bile. When exposed to bile salts, these metastable vesicles
      undergo various structural rearrangements. We have examined the effects of three
      different bile salts, taurocholate (TC), tauroursodeoxycholate (TUDC), and
      taurodeoxycholate (TDC), on the stability of sonicated lecithin vesicles
      containing various amounts of cholesterol. Vesicle growth was probed by turbidity
      measurements, quasi-elastic light scattering, and a resonance energy transfer
      lipid-mixing assay. Leakage of internal contents was monitored by encapsulation
      of fluorescence probes in vesicles. At low bile salt-to-lecithin ratios (TC/L or
      TUDC/L < 1), pure lecithin vesicles do not grow, but exhibit slow intervesicular
      mixing of lipids as well as gradual leakage. At high BS/L (TC/L or TUDC/L > 5),
      pure lecithin vesicles are solubilized into mixed micelles with a concomitant
      decrease in the overall particle size. In this regime, extensive leakage and
      lipid mixing occur instantaneously after exposure to bile salt. At intermediate
      BS/L (1 < TC/L or TUDC/L < 5), vesicles grow with time, and the rates of both
      leakage and lipid mixing are rapid. The data suggest that vesicles grow by the
      transfer of lecithin and cholesterol via diffusion in the aqueous medium. The
      addition of cholesterol to lecithin vesicles reduces leakage dramatically and
      increases the amount of BS required for complete solubilization of vesicles. The
      more hydrophobic TDC induces vesicle growth at a lower BS/L than does TC or TUDC.
      These results demonstrate the physiologic forms of lipid microstructures during
      bile formation and explain how the hydrophilic-hydrophobic balance of BS mixtures
      may profoundly affect the early stages of CH gallstone formation.

PMID- 9153404
TI  - Characterization of a site-directed mutant of cytochrome b5 designed to alter
      axial imidazole ligand plane orientation.
AB  - Mutants of cytochrome b5 were designed to achieve reorientation of individual
      axial imidazole ligands. The orientation of the axial ligand planes is thought to
      modulate the reduction potential of bis(imidazole) axially ligated heme proteins.
      The A67V mutation achieved this goal through the substitution of a bulkier,
      hydrophobic ligand for a residue, in the sterically hindered hydrophobic heme
      binding pocket. Solution structures of mutant and wild-type proteins in the
      region of the mutation were calculated using restraints obtained from 1H and 15N
      2D homonuclear and heteronuclear NMR spectra and 1H-15N 3D heteronuclear NMR
      spectra. More than 10 restraints per residue were used in the refinement of both
      structures. Average local rmsd for 20 refined structures was 0.30 A for the wild
      type structure and 0.38 A for the A67V mutant. The transfer of amide proton
      resonance assignments from wild-type to the mutant protein was achieved through
      overlays of 15N-1H heteronuclear correlation spectra of the reduced proteins.
      Side chain assignments and sequential assignments were established using
      conventional assignment strategies. Calculation of the orientation of the
      components of the anisotropic paramagnetic susceptibility tensor, using methods
      similar to procedures applied to the wild-type protein, shows that the
      orientation of the in-plane components are identical in the wild-type and mutant
      proteins. However, the orientation of the z-component of the susceptibility
      tensor calculated for the mutant protein differs by 17 degrees for the A-form and
      by 11 degrees for the B-form from the orientation calculated for the wild-type
      protein. The rotation of the z-component of the susceptibility tensor (toward the
      delta meso proton) is in the same direction and is of the same magnitude as the
      rotation of the H63 imidazole ring induced by mutation.

PMID- 9153405
TI  - Effect of axial ligand plane reorientation on electronic and electrochemical
      properties observed in the A67V mutant of rat cytochrome b5.
AB  - Mutational studies directed at evaluating the effect of the axial ligand plane
      orientation on electrochemical properties of cytochrome b5 have been performed.
      As described in the previous paper, structural consequences of one of these
      mutations, the A67V mutation, have been evaluated using NMR solution methods. The
      lack of large shifts relative to the wild-type protein in both the imidazole
      Ndelta nitrogen and proton resonances of the H63 imidazole ring indicates that
      the hydrogen bond between the carbonyl of F58 and the imidazole ring of H63
      remains intact in this mutant. Effects of the imidazole plane reorientation on
      the Fe d-orbitals were evaluated on the basis of interpretation of EPR spectra,
      near-infrared bands associated with ligand-to-metal charge transfer transitions,
      reorientation of the anisotropy of the paramagnetic center determined by
      calculation of pseudocontact shifts, and the temperature dependence of the
      contact-shifted resonances. The dominant effect of the imidazole reorientation
      appears to have been a destabilization of the d(xz) orbital energy and a
      reorientation of the d(pi) orbitals. This is surprising in light of the -20 mV
      shift in the reduction potential of the mutant relative to the wild-type protein
      and indicates that a destabilization of d(yz)-orbital energy level of the reduced
      state dictates the observed change in reduction potential. Measured values for
      the reorganizational energy and heterogeneous electron transfer rates were
      indistinguishable for wild-type and mutant proteins. This is perhaps surprising,
      given significant differences in the pattern of electron delocalization into the
      porphyrin ring observed as significantly altered contact shift patterns.
      Mutational studies perturbing the H39 imidazole were also performed but with more
      limited success.

PMID- 9153406
TI  - The isolation and characterization of purified heterocomplexes of recombinant
      retinoic acid receptor and retinoid X receptor ligand binding domains.
AB  - Retinoic acid exerts many of its biological effects by interaction with
      heterocomplexes of nuclear retinoic acid receptors (RARs) and retinoid X
      receptors (RXRs). To further examine this interaction, a glutathione S
      transferase (GST) fusion protein containing the ligand binding domain of human
      RXR alpha has been used to copurify the ligand binding domain of human RAR gamma
      by affinity chromatography over glutathione-agarose. Complexes of recombinant RAR
      RXR ligand binding domains retaining full ligand binding capacity were purified,
      and their interactions with various retinoids were characterized by fluorometric
      titration and photoaffinity labeling. Analyses of the distribution of limiting
      amounts of [3H]-all-trans-retinoic acid between cytoplasmic retinoic acid binding
      proteins, CRABP-I and CRABP-II, and the purified heterocomplexes indicate that
      all-trans-retinoic acid binds with comparable affinity to CRABP-I and the
      heterocomplexes, but with approximately 10-fold less affinity to CRABP-II. The
      aromatic retinoid acitretin, which is used in the treatment of psoriasis, binds
      relatively poorly to the purified heterocomplexes, although it binds with high
      affinity to the CRABPs. Acitretin displaces [3H]-all-trans-retinoic acid from the
      CRABPs and increases retinoic acid occupancy of the heterocomplexes. These
      results suggest that certain retinoids could potentially perturb the distribution
      of endogenous retinoic acid between the CRABPs and the nuclear receptors and thus
      affect retinoid signaling. The purified recombinant complexes should provide a
      useful model system for further structural analysis of the dimerization interface
      between the RAR and RXR ligand binding domains.

PMID- 9153407
TI  - Insufficiency of self-phosphorylation for the activation of epidermal growth
      factor receptor.
AB  - Polyclonal immunoglobulins were produced against the carboxy terminus, -SEFIGA,
      of the receptor for epidermal growth factor (EGF). The addition of these
      immunoglobulins to a solution containing EGF receptor resulted in the activation
      of its protein tyrosine kinase. The levels of activation were assessed by
      measuring the initial velocities of the phosphorylation of the tyrosine in
      angiotensin II. The enzymatic activity induced by the immunoglobulins was
      significant, usually 50-70% of the maximum activity induced by EGF, and the
      induction occurred over a narrow range of concentration of the immunoglobulins.
      In order to achieve the activation, the immunoglobulins had to be bivalent; the
      addition of monovalent Fab fragments to EGF receptor did not produce any
      activation of the protein tyrosine kinase. The activation produced by the
      immunoglobulins was found to be reversible upon the addition of the synthetic
      peptide SEFIGA against which the immunoglobulins had been produced. Self
      phosphorylation of the EGF receptor also occurred as the enzyme was activated by
      the immunoglobulins. Tryptic peptide maps demonstrated that the self
      phosphorylation caused by the immunoglobulins had the same signature as that
      produced by EGF. When the synthetic peptide that had been used as the hapten was
      added to EGF receptor that had been self-phosphorylated in the presence of the
      immunoglobulins, the stimulated enzymatic activity was lost even though the
      protein remained phosphorylated. It follows from the results of deletion mutation
      [Walton, G. M., Chen, W. S., Rosenfeld, M. G., & Gill, G. N. (1990) J. Biol.
      Chem. 265, 1750-1754] and the results reported here that self-phosphorylation is
      neither necessary nor sufficient for the activation of EGF receptor.

PMID- 9153408
TI  - Phosphatidylcholine and phosphatidylethanolamine behave as substrates of the
      human MDR1 P-glycoprotein.
AB  - The multidrug resistant cell line CEM/VBL300 and the parental CEM T-lymphoblastic
      cell line from which it was derived were used to study the accumulation of
      fluorescent phospholipid analogs of phosphatidylcholine (PC),
      phosphatidylethanolamine (PE), and phosphatidylserine (PS). The fluorescent
      analogs NBD-PC, NBD-PE, and NBD-PS and [3H]PC were delivered in liposomes
      prepared by ethanol injection. Fluorescence microscopy demonstrated decreased
      accumulation of the NBD-PC analog in the multidrug resistant cell line compared
      to the parental cell line. Verapamil enhanced NBD-PC accumulation in the
      resistant cells. Similar results were obtained with insect cells expressing high
      levels of recombinant human MDR1. Elimination of NBD fluorescence on the outer
      leaflet of the plasma membrane with dithionite permitted quantification of the
      internal cellular fluorescence by FACS analysis. The drug resistant CEM/VBL300
      cells accumulated approximately 10% the amount of NBD-PE and 20% the amount of
      NBD-PC compared to CEM drug sensitive cells. No difference in internal
      accumulation of NBD-PS was found between the drug resistant and drug sensitive
      cell lines. The internal accumulation of NBD-PE and NBD-PC was enhanced by the
      MDR reversal agents verapamil, cyclosporin A, and SDZ PSC 833 in the CEM/VBL300
      cells but not in the CEM cells. The increased accumulation was dose dependent,
      and the relative potency of the reversal agents paralleled their ability to
      circumvent multidrug resistance. In addition, the monoclonal antibody UIC2
      directed against the P-glycoprotein produced similar results. The evidence
      presented here suggests that PC and PE but not PS behave as substrates for human
      MDR1 P-glycoprotein.

PMID- 9153409
TI  - Lipid bilayer electrostatic energy, curvature stress, and assembly of gramicidin
      channels.
AB  - Hydrophobic interactions between lipid bilayers and imbedded membrane proteins
      couple protein conformation to the mechanical properties of the bilayer. This
      coupling is widely assumed to account for the regulation of membrane protein
      function by the membrane lipids' propensity to form nonbilayer phases, which will
      produce a curvature stress in the bilayer. Nevertheless, there is only limited
      experimental evidence for an effect of bilayer curvature stress on membrane
      protein structure. We show that alterations in curvature stress, due to
      alterations in the electrostatic energy of dioleoylphosphatidylserine bilayers,
      modulate the structurally well-defined gramicidin A monomer <--> dimer reaction.
      Maneuvers that decrease the electrostatic energy of the unperturbed bilayer
      promote channel dissociation; we measure the change in interaction energy. The
      bilayer electrostatic energy thus can affect membrane protein structure by a
      mechanism that does not involve the electrostatic field across the bilayer, but
      rather electrostatic interactions among the phospholipid head groups in each
      monolayer which affect the bilayer curvature stress. These results provide
      further evidence for the importance of mechanical interactions between a bilayer
      and its imbedded proteins for protein structure and function.

PMID- 9153410
TI  - Flip-flop is slow and rate limiting for the movement of long chain anthroyloxy
      fatty acids across lipid vesicles.
AB  - An issue that is central to understanding cellular fatty acid (FA) metabolism is
      whether physiologic transport of FA across cell membranes requires protein
      mediation or can be satisfied by the rate of spontaneous movement through the
      lipid phase. For this reason, considerable effort has been devoted to determining
      the rate-limiting steps for transport of FA across pure lipid bilayer membranes.
      Previously, we found that transbilayer flip-flop was the rate-limiting step for
      transport of long chain anthroyloxy FA (AOFA) across lipid bilayers and that the
      times for long chain AOFA flip-flop were > or = 100 s, yielding rate constants
      for flip-flop (k(ff)) that were < or = 0.01 s(-1) [Storch, J., & Kleinfeld, A. M.
      (1986) Biochemistry 25, 1717-1726; Kleinfeld, A. M., & Storch, J. (1993)
      Biochemistry 32, 2053-2061]. In those studies, k(ff) values were inferred from
      the time course of AOFA transfer between lipid vesicles. Recently, Kamp et al.
      [Kamp, F., Zakim, D., Zhang, F., Noy, N., & Hamilton, J. A. (1995) Biochemistry
      34, 11928-11937], using pyranine trapped within lipid vesicles to detect flip
      flop more directly, have reported that flip-flop rates of long chain AOFA are
      extremely rapid (k(ff) > 10 s(-1)) and are not rate limiting for transbilayer
      transport. Because no defect was apparent in our previous measurements, we have
      extended, for AOFA, the pyranine method of Kamp et al. (1995) by using stopped
      flow fluorometry to resolve flip-flop rates of both short and long chain AOFA in
      vesicles. In addition, we have monitored the time course of transbilayer AOFA
      flip-flop using carboxyfluorescein (CF) trapped within the lipid vesicles as a
      resonance energy transfer (RET) acceptor of AO fluorescence. The differential
      quenching of AOFA fluorescence in the outer and inner leaflets of the bilayer
      allows flip-flop to be separated from the time course of AOFA binding to the
      vesicles. Results obtained from both the pyranine and CF methods indicate, in
      agreement with our previous results, that flip-flop of the long chain AOFA is
      slow relative to either the binding or the rate of dissociation from the vesicle.
      In particular, we find that the time constant (tau) for pyranine quenching by 2
      AO-palmitate (2-AOPA) was > 40 s and that k(ff) obtained from RET in CF vesicles
      was about 0.003 s(-1). Also, in contrast to Kamp et al. (1995) who reported that
      k(ff) values were independent of FA chain length or structure for the C-12 to C
      18 native and the C-18 AOFA within a factor of 2, we find that the rate of
      pyranine quenching for the shorter chain 11-AO-undecanoic acid is more than 50
      fold faster than for the longer chain AOFA. We conclude, therefore, that
      transbilayer transport of the AOFA is limited by the rate of flip-flop and that
      this rate is a sensitive function of the AOFA structure.

PMID- 9153411
TI  - Dual specificity of Src homology 2 domains for phosphotyrosine peptide ligands.
AB  - SH2 domains mediate protein-protein interactions and are involved in a wide range
      of intracellular signaling events. SH2 domains are 100-amino acid stretches of
      protein that bind to other proteins containing phosphotyrosine residues. A
      current major research goal is formulation of the structural principles which
      govern peptide-binding specificity in SH2 domains. Several structures (both X-ray
      and NMR) of SH2 domains have now been determined. Short peptide fragments on the
      carboxyl-terminal side of the phosphotyrosine residue carry the sequence specific
      information for SH2 recognition. The bound peptides are held in an extended
      conformation. However, for the GRB2 SH2 domain, the peptide adopts a beta-turn as
      the motif for recognition [Rahuel, J., et al. (1996) Nat. Struct. Biol. 3, 586
      589]. Our SAR data and molecular modeling studies suggest that many SH2 domains,
      such as the SH2 domains of Lck, Src, and p85, can interact with high affinity
      with short peptide sequences at least in two ways which are sequence-dependent.
      The peptide forms either an extended chain across the D-strand of SH2 domains
      with anchors at pY and pY+3 or, as in the case of GRB2 SH2, a beta-turn with
      anchors at pY and pY+2. Due to a bulky tryptophan in its EF1 loop, GRB2 SH2
      cannot bind peptide conformations such as the extended chain and thus has a
      unique specificity.

PMID- 9153412
TI  - Botulinum neurotoxin B inhibits insulin-stimulated glucose uptake into 3T3-L1
      adipocytes and cleaves cellubrevin unlike type A toxin which failed to proteolyze
      the SNAP-23 present.
AB  - Types A, B, and C1 botulinum neurotoxin (BoNT), a group of selective Zn2+
      dependent endoproteases, have been instrumental in demonstrating that their
      respective substrates [synaptosomal-associated protein with Mr = 25 kDa (SNAP
      25), synaptobrevin (Sbr), and syntaxin] are essential for regulated exocytosis
      from nerve terminals and neuroendocrine cells. The colocalization of Sbr, or its
      homologue cellubrevin (Cbr), in the majority of the glucose transporter-isotype 4
      (GLUT4)-containing vesicles from adipocytes implicates their involvement in
      insulin-stimulated glucose uptake, which results in part from enhanced fusion of
      these vesicles with the plasmalemma. In this study, exposure of cultured 3T3-L1
      adipocytes to BoNT/B in a low-ionic strength medium was found to block insulin
      evoked glucose uptake by up to 64%. BoNT/B was shown by immunoblotting to cause
      extensive proteolysis of Cbr and Sbr resulting in a significant blockade of the
      insulin-stimulated translocation of GLUT4 to the plasmalemma. This establishes
      that these two toxin substrates contribute to the insulin-regulated fusion of
      GLUT4-containing vesicles with the plasmalemma, at least in this differentiated
      3T3-L1 clone. Although SNAP-25 was not detectable in the differentiated
      adipocytes, its functional homologue SNAP-23 is abundant and largely confined to
      the plasmalemma. SNAP-23 proved to be resistant to cleavage by BoNT/A. Consistent
      with these results, type A did not block insulin-induced glucose uptake,
      precluding a demonstration of its likely importance in this process.

PMID- 9153413
TI  - Altered sialylation of osteopontin prevents its receptor-mediated binding on the
      surface of oncogenically transformed tsB77 cells.
AB  - It has been reported previously that oncogenically transformed cells secrete
      different molecular forms of osteopontin (OPN), a sialic acid-rich, adhesive,
      phosphoglycoprotein, than OPNs secreted by their nontransformed counterparts.
      However, the origin of the OPN isoform secreted by the transformed cells and
      whether it has different physiological properties which may serve transformation
      specific functions remain poorly understood. Here, we report that Rat-1 cells
      transformed by a temperature-sensitive mutant of Rous sarcoma virus (tsB77)
      secrete two discrete molecular forms of OPN, a 69-kDa OPN at the nonpermissive
      temperature (41 degrees C) and a 62-kDa form at the permissive temperature (34
      degrees C). However, tsB77 cells at both temperatures transcribe a single 1.6 kb
      OPN mRNA and contain only the 69-kDa form of OPN intracellularly, suggesting that
      the 69-kDa OPN is modified to the 62-kDa form prior to or immediately after
      secretion by cells at 34 degrees C. We ruled out proteolytic cleavage,
      differential phosphorylation, or lack of N- or O-linked carbohydrates as the
      possible mechanism, but found that the 62-kDa OPN contains significantly reduced
      levels of sialic acid, as compared to its 69-kDa form. The binding assays using
      32P-labeled OPN revealed that only the 69-kDa OPN, not its 62-kDa form, undergoes
      receptor-mediated localization on the cell surface, although tsB77 cells
      synthesize OPN receptors (alpha(v)beta3 integrins) at both permissive and
      nonpermissive temperatures. Furthermore, 125I-labeled purified milk OPN, which is
      highly sialylated and shows cell surface binding, upon digestion with
      neuraminidase failed to interact with the cell surface. Taken together, these
      results suggest that the difference between the 69-kDa and 62-kDa isoforms of OPN
      resides in their sialic acid content, and sialylation of OPN is crucial for its
      receptor-mediated binding on tsB77 cells. The data presented here demonstrate for
      the first time a physiological role of sialic acids in this protein, and raise
      the possibility that oncogenically transformed tsB77 cells may exploit the lack
      of OPN-receptor interactions for their invasive behavior.

PMID- 9153414
TI  - Arrest of replication fork progression at sites of topoisomerase II-mediated DNA
      cleavage in human leukemia CEM cells incubated with VM-26.
AB  - Recent studies have shown that the anticancer drugs VM-26 and mitoxantrone
      stabilize preferentially the binding of topoisomerase IIalpha to replicating
      compared to nonreplicating DNA. To further understand the mechanisms by which
      cleavable complex-forming topoisomerase II inhibitors interfere with DNA
      replication, we examined the effects of VM-26 on this process in human leukemia
      CEM cells. Both the inhibition of DNA synthesis and cell survival were directly
      related to the total amount of drug-stabilized cleavable complexes formed in VM
      26-treated cells. DNA chain elongation was also inhibited in a concentration
      dependent fashion in these cells, which suggested that VM-26-stabilized cleavable
      complexes interfered with the movement of DNA replication forks. To test this
      hypothesis directly, we monitored replication fork progression at a specific site
      of VM-26-induced DNA cleavage. A topoisomerase II-mediated cleavage site was
      detected in the first exon of the c-myc gene in VM-26-treated cells. This
      cleavage site was downstream of a putative replication origin located in the 5'
      flanking region of the gene. Replication forks, which moved through this region
      of the c-myc gene in the 5' to 3' direction, were specifically arrested at this
      site in VM-26-treated cells, but not in untreated or aphidicolin-treated cells.
      These studies provide the first direct evidence that a VM-26-stabilized
      topoisomerase II-DNA cleavable complex acts as a replication fork barrier at a
      specific genomic site in mammalian cells. Furthermore, the data support the
      hypothesis that the replication fork arrest induced by cleavable complex-forming
      topoisomerase II inhibitors leads to the generation of irreversible DNA damage
      and cytotoxicity in proliferating cells.

PMID- 9153415
TI  - Nucleotide-induced stable complex formation by HIV-1 reverse transcriptase.
AB  - Nondenaturing gel electrophoresis was used to study the nucleotide substrate
      induced conformational change in reverse transcriptase (RT) of human
      immunodeficiency virus type 1 (HIV-1). Dead-end complex was formed between HIV-1
      RT, dideoxynucleotide chain-terminated primer, and DNA template in the presence
      of deoxynucleotide triphosphate (dNTP) complementary to the next position on the
      template. Complexes which form in the absence of the next complementary dNTP were
      disrupted by adding excess poly(rA)/oligo(dT) or heparin just prior to
      electrophoresis. Dead-end complex formation by noncomplementary dNTP's or
      ribonucleotides was at least 2000-fold less efficient than with the complementary
      nucleotide. When dA was the next nucleotide on the template, analogues of dTTP
      supported dead-end complex formation with increased apparent Kd (dTTP < dideoxy
      TTP approximately alpha-thio-dTTP < dUTP < 3'-azidothymidine triphosphate). A
      similar relationship was observed for dGTP analogues across from dC on the
      template (dGTP < dideoxy-GTP < alpha-thio-dGTP << dITP < dideoxy-ITP). The
      optimal length of the primer/template duplex region for dead-end complex
      formation was between 20 and 32 base pairs. Primer-template with a mismatched
      primer terminus did not support dead-end complex formation, and primer terminated
      with 3'-azidothymidine formed dead-end complex with 25-fold elevated apparent Kd.
      By contrast, dead-end complex formation on primer terminated with dideoxy-IMP
      base paired with dC on the template was more efficient than on primer terminated
      with dideoxy-GMP. Implications for the mechanisms of discrimination between
      nucleotide analogues by HIV-1 RT are discussed.

PMID- 9153416
TI  - Mutating a conserved motif of the HIV-1 reverse transcriptase palm subdomain
      alters primer utilization.
AB  - In order to investigate how primer grip residues of human immunodeficiency virus
      type 1 reverse transcriptase (HIV-1 RT) contribute toward the architecture of its
      palm subdomain and neighboring structural elements, the DNA polymerase and
      ribonuclease H (RNase H) activities of enzymes bearing aromatic substitutions at
      Trp229 and Tyr232 of the catalytically-competent p66 subunit were evaluated.
      Although all mutants retained RNase H function, the manner in which different RNA
      DNA hybrids were hydrolyzed was affected. Depending on the nature of the
      substitution, DNA-dependent DNA synthesis was (i) unaffected, (ii) interrupted
      shortly after initiation, or (iii) stalled when the replication machinery
      encountered an intramolecular duplex on the single-stranded template. Evaluating
      (-) strand strong-stop DNA synthesis on an RNA template derived from the viral
      genome raises the additional possibility that DNA and RNA primers might be
      differentially recognized by the retroviral polymerase. In support of this, all
      mutants were unable to extend the HIV-1 polypurine tract (PPT) RNA primer into
      (+) strand DNA, despite supporting the equivalent event from an
      oligodeoxynucleotide primer. Collectively, our data illustrate that subtle
      alterations to primer grip architecture may manifest themselves in discrimination
      between oligoribo- and oligodeoxyribonucleic acid primers.

PMID- 9153417
TI  - Specific recognition of O6-methylguanine in DNA by active site mutants of human
      O6-methylguanine-DNA methyltransferase.
AB  - O6-Methylguanine-DNA methyltransferase (MGMT), a ubiquitous DNA repair protein,
      acts as a monomer in removing the mutagenic DNA adduct O6-alkylguanine (induced
      by alkylating carcinogens) via a stoichiometric reaction. The alkyl group is
      transferred without a cofactor to a specific cysteine acceptor residue of MGMT,
      Cys-145 in the case of human MGMT, containing 207 amino acid residues and thereby
      inactivates the protein. As a prelude to the investigation of the reaction
      mechanism of human MGMT by elucidation of its structure in free and substrate
      bound forms via NMR spectroscopy and X-ray crystallography, two types of MGMT
      mutants were generated and characterized. First, systematic deletion analysis of
      the protein was carried out to determine the smallest size at which it is active
      or inactive but forms a stable complex with the substrate and so may be useful
      for NMR spetroscopic analysis. Deletion of more than 8 or 31 residues from the
      amino or carboxyl terminus, respectively, led to the loss of both activity and
      substrate binding. Removal of Arg-9 or Leu-176 and distal residues inactivated
      the protein, presumably by altering its tertiary structure. On the basis of the
      criteria of bacterial overexpression and solubility, the mutant MGMT with
      deletion of 28 residues at the carboxyl terminus should be suitable for NMR
      studies. In the second approach, we examined mutants at the active site (Cys-145)
      that retain substrate binding. Inactive C145A and C145S substitution mutants were
      found to form specific and stable complexes with an O6-methylguanine (m6G)
      containing oligonucleotide substrate. Wild type MGMT also formed a similar
      complex, but only as a transient intermediate. Footprinting studies indicated a
      strong discriminatory effect of the base adduct on the binding of C145A to
      substrate DNA; 17-18 nucleotides on the m6G-containing strand and 13-14
      nucleotides in the complementary strand spanning the base adduct were protected
      from DNase I digestion by the mutant protein. These results, as well as the
      identical protease sensitivity of the wild type and mutant proteins, suggest
      minimal structural change due to conservative mutations at the active site. Thus,
      the mutant proteins may be utilized for solving the structure and mechanism of
      human MGMT.

PMID- 9153418
TI  - Kinetic analysis of the endonuclease activity of phage lambda terminase: assembly
      of a catalytically competent nicking complex is rate-limiting.
AB  - The terminase enzyme from bacteriophage lambda is responsible for excision of a
      single genome from a concatameric DNA precursor and its insertion into an empty
      viral procapsid. The enzyme possesses a site-specific endonuclease activity which
      is responsible for excision of the viral genome and the formation of the 12 base
      pair single-stranded "sticky" ends of mature lambda DNA. We have previously
      reported a kinetic analysis of the endonuclease activity of lambda terminase
      which showed an enzyme concentration-dependent change in the kinetic time course
      of the reaction [Tomka, M. A., & Catalano, C. E. (1993b) J. Biol. Chem. 268, 3056
      3065]. We presented a model which suggested that the rate-limiting step in the
      nuclease reaction was the assembly of a catalytically competent prenicking
      complex. Here, we provide additional evidence for a slow assembly step in the
      nuclease reaction and demonstrate that the observed rate is affected by protein
      concentration, but not by the length of the DNA substrate. Consistent with our
      model, preincubation of terminase with DNA also yields an observable fast phase
      of the reaction, but only when large (> or = 3 kb) DNA substrates are used.
      Finally, we present data which demonstrate that phage lambda terminase can
      efficiently utilize DNA from the closely related phage phi21 as an endonuclease
      substrate and that the enzyme binds efficiently to the cosB region of both phage
      genomes. The implications of these results with respect to the assembly of a
      catalytically competent nucleoprotein complex required to initiate genome
      packaging are discussed.

PMID- 9153419
TI  - Amide backbone and water-related H/D isotope effects on the dynamics of a protein
      folding reaction.
AB  - The denaturant-dependent relaxation kinetics of folding and unfolding of an
      isolated all-beta domain of rat CD2 have been measured at 25 degrees C in four
      isotopic conditions: with a protonated (amide) backbone in H2O and in D2O and
      with a deuterated backbone in H2O and in D2O. The data show that this structure,
      which contains no disulfide bonds, folds through a rapidly formed intermediate
      (pathway U-I-F) and that all free energy changes between states are insensitive
      to isotopic substitution of the amide groups required for intrachain hydrogen
      bonding. However, the folding reaction is significantly influenced by the nature
      of the bulk solvent. In D2O, the stability of each state in the folding pathway,
      relative to the unfolded molecule, is enhanced to a degree which is proportional
      to its m value, a measure of the exposure of nonpolar protein groups to the
      solvent. Together these observations suggest that, at this temperature, the
      solvent isotope effect arises from enhanced hydrophobic interactions which, in
      turn, results from an increased strength of the solvent-solvent hydrogen bond in
      D2O. Apart from emphasizing the role of bonds between solvent molecules in
      protein folding, the results also have practical implications for amide H/D
      exchange studies. While the replacement of amide protons by deuterons will not
      affect the protein's stability during exchange experiments, it is important to
      account for the isotopic influence of the solvent in which the exchange reaction
      is performed.

PMID- 9153420
TI  - Kinetic evidence for folding and unfolding intermediates in staphylococcal
      nuclease.
AB  - The complex kinetic behavior commonly observed in protein folding studies
      suggests that a heterogeneous population of molecules exists in solution and that
      a number of discrete steps are involved in the conversion of unfolded molecules
      to the fully native form. A central issue in protein folding is whether any of
      these kinetic events represent conformational steps important for efficient
      folding rather than side reactions caused by slow steps such as proline
      isomerization or misfolding of the polypeptide chain. In order to address this
      question, we used stopped-flow fluorescence techniques to characterize the
      kinetic mechanism of folding and unfolding for a Pro- variant of SNase in which
      all six proline residues were replaced by glycines or alanines. Compared to the
      wild-type protein, which exhibits a series of proline-dependent slow folding
      phases, the folding kinetics of Pro- SNase were much simpler, which made
      quantitative kinetic analysis possible. Despite the absence of prolines or other
      complicating factors, the folding kinetics still contain several phases and
      exhibit a complex denaturant dependence. The GuHCl dependence of the major
      observable folding phase and a distinct lag in the appearance of the native state
      provide clear evidence for an early folding intermediate. The fluorescence of
      Trp140 in the alpha-helical domain is insensitive to the formation of this early
      intermediate, which is consistent with a partially folded state with a stable
      beta-domain and a largely disordered alpha-helical region. A second intermediate
      is required to model the kinetics of unfolding for the Pro- variant, which shows
      evidence for a denaturant-induced change in the rate-limiting unfolding step.
      With the inclusion of these two intermediates, we are able to completely model
      the major phase(s) in both folding and unfolding across a wide range of
      denaturant concentrations using a sequential four-state folding mechanism. In
      order to model the minor slow phase observed for the Pro- mutant, a six-state
      scheme containing a parallel pathway originating from a distinct unfolded state
      was required. The properties of this alternate unfolded conformation are
      consistent with those expected due to the presence of a non-prolyl cis peptide
      bond. To test the kinetic model, we used simulations based on the six-state
      scheme and were able to completely reproduce the folding kinetics for Pro- SNase
      across a range of denaturant concentrations.

PMID- 9153421
TI  - Thymosin beta 4 binds actin in an extended conformation and contacts both the
      barbed and pointed ends.
AB  - The beta-thymosins are a family of highly polar peptides which serve in vivo to
      maintain a reservoir of unpolymerized actin monomers. In vitro, beta-thymosins
      form 1:1 complexes with actin monomers and inhibit both polymerization and
      exchange of the bound nucleotide. Circular dichroism data indicate that free
      thymosin beta 4 is predominantly unstructured, containing at most six residues of
      alpha-helix, and that up to six additional residues may adopt an alpha-helical
      conformation upon binding actin. NMR data indicate that many parts of thymosin
      beta 4 are not in tight contact with actin. Contacts between specific residues in
      actin and thymosin beta 4 were identified by zero-length cross-linking followed
      by isolation and sequencing of cross-linked peptides. After carbodiimide-mediated
      cross-linking, Lys-3 of thymosin beta 4 was cross-linked to Glu-167 of actin, and
      Lys-18 of thymosin beta 4 was cross-linked to one of the the N-terminal acidic
      residues of actin (Asp-1-Glu-4); the cross-linked actin residues lie within
      subdomains 3 and 1, respectively. These two contacts flank the alpha-helical
      region of thymosin beta 4 and place it on the barbed end; thymosin beta 4 can
      thus block actin polymerization sterically. After transglutaminase-mediated cross
      linking, Lys-38 of thymosin beta 4 was cross-linked to Gln-41 of actin, placing
      the C-terminal region of thymosin beta 4 in contact with subdomain 2 on the
      pointed end; thymosin beta 4 may sterically block actin polymerization at the
      pointed end as well as the barbed end of the monomer. The distance between the
      pointed-end and barbed-end contacts requires that the C-terminal half of thymosin
      beta 4 be in a predominantly extended conformation.

PMID- 9153422
TI  - Cytoplasmic chaperonin containing TCP-1: structural and functional
      characterization.
AB  - Actin and tubulin polypeptide chains acquire their native conformation in the
      presence of the cytoplasmic chaperonin containing TCP-1 (CCT, also called TRiC)
      and, in the case of alpha- and beta-tubulin, additional protein cofactors. It has
      been previously demonstrated that nucleotide exchange and ATP hydrolysis act to
      switch CCT between conformations that interact either strongly or weakly with
      unfolded substrates [Melki, R., & Cowan, N.J. (1994) Mol. Cell. Biol. 14, 2895
      2904]. The present study further documents the conformational changes and
      function of CCT. It is first shown, by the use of a range of labeled denatured
      substrate proteins and a radiolabeled total soluble HeLa cell extract, that CCT
      in the absence of nucleotides can bind any of a large number of proteins in vitro
      with high affinity. Second, by the use of denatured labeled beta-actin and beta
      tubulin as model substrates for binding to CCT, we demonstrate that the CCT
      particle can contain two substrate protein chains simultaneously. Third, by
      electron microscopy, sedimentation velocity, and intrinsic fluorescence
      measurements, we document the conformational difference between CCT in its ATP-
      and ADP-bound forms, as well as the change that results from binding of substrate
      protein. A model summarizes substrate association with CCT and the role of the
      nucleotide in regulating the affinity of CCT for target proteins.

PMID- 9153423
TI  - Acyl chain unsaturation and vesicle curvature alter outer leaflet packing and
      promote poly(ethylene glycol)-mediated membrane fusion.
AB  - The poly(ethylene glycol) (PEG)-induced fusion of sonicated, unilamellar vesicles
      (SUV) and large, unilamellar vesicles (LUV) composed of a variety of
      phosphatidylcholine species was compared using two assays for the mixing and
      leakage of internal vesicle contents. In the first [Lentz et al. (1992)
      Biochemistry, 31, 2643], disodium 8-aminonaphthalene-1,3,6-trisulfonate (ANTS)
      fluorescence is quenched by co-encapsulated N,N'-p-xylylenebis(pyridinium
      bromide) (DPX). For this assay, interference by the fluorescence of impurities in
      PEG demands that the PEG content of the sample be reduced by dilution before
      measurements are taken. The second assay [Viguera et al. (1993) Biochemistry, 32,
      3708] monitors the fluorescence of Tb3+ complexed with dipicolinic acid (DPA)
      directly in concentrated PEG solutions. The two assays gave identical fusion
      profiles for egg PC SUVs treated with increasing concentrations of PEG,
      demonstrating that fusion occurs in the dehydrated state in the presence of PEG
      and does not require dilution. Comparison of results obtained with lipid species
      of varying degrees of unsaturation incorporated into either SUV or LUV suggested
      that acyl chain unsaturation and high membrane curvature combine to favor fusion
      of pure phosphatidylcholine membranes. There was a clear correlation between the
      fluorescence lifetime or the order parameter of the membrane probe 1-(4
      trimethylammonium)-6-phenyl-1,3,5-hexatriene (TMA-DPH) in different membranes and
      the concentration of PEG needed to induce fusion of these membranes. However, the
      ratios of TMA-DPH lifetimes measured in D2O versus H2O buffers were the same for
      different lipid species, indicating that probe penetration was not very different
      for different lipid species. The results suggest that the combined effect of high
      membrane curvature and extensive chain unsaturation is an enhanced rate of lipid
      motion in the upper region of the bilayer, reflective of decreased packing
      density in the outer leaflet of unsaturated SUV bilayers, probably allowing for
      enhanced water penetration leading to an enhanced probability of fusion.

PMID- 9153424
TI  - Mechanisms of stabilization of the insulin hexamer through allosteric ligand
      interactions.
AB  - The insulin hexamer is an allosteric protein capable of undergoing transitions
      between three conformational states: T6, T3R3, and R6. These transitions are
      mediated by the binding of phenolic compounds to the R-state subunits, which
      provide positive homotropic effects, and by the coordination of anions to the
      bound metal ions, which act as heterotropic effectors. Since the insulin monomer
      is far more susceptible than the hexamer to thermal, mechanical, and chemical
      degradation, insulin-dependent diabetic patients rely on pharmaceutical
      preparations of the Zn-insulin hexamer, which act as stable forms of the
      biologically active monomeric insulin. In this study, the chromophoric chelator
      2,2',2"-terpyridine (terpy) has been used as a kinetic probe of insulin hexamer
      stability to measure the effect of homotropic and heterotropic effectors on the
      dissociation kinetics of the Zn2+- and Co2+-insulin hexamer complexes. We show
      that the reaction between terpy and the R-state-bound metal ion is limited by the
      T3R3 <==> T6 or R6 <==> T3R3 conformational transition steps and the dissociation
      of one anionic ligand, or one anionic ligand and three phenolic ligand molecules,
      respectively, for T3R3 and R6. Consequently, because the activation energies of
      these steps are dominated by the ground-state stabilization energy of the R-state
      species, the kinetic stabilization of the insulin hexamer toward terpy-induced
      dissociation is linked to the thermodynamic stabilization of the hexamer. The
      mass action effect of anion binding and, foremost, of phenolic ligand binding
      provides the major mechanism of stabilization, resulting in the tightening of the
      tertiary and quaternary hexamer structures. Using this kinetic method, we show
      that the R6 conformation of Zn-insulin in the presence of Cl- ion and resorcinol
      is > 1.5 million-fold more stable than the T3 units of T6 and T3R3 and > 70,000
      fold more stable than the R3 unit of T3R3. Furthermore, the stabilization effect
      is correlated with the affinity of the ligands: the tighter the binding, the
      slower the reaction between terpy and R-state-bound metal ion. These concepts
      provide a new basis for the pharmaceutical improvement of the physicochemical
      stability of formulations both for native insulin and for fast-acting monomeric
      insulin analogues through ligand-mediated allosteric interactions.

PMID- 9153425
TI  - Two reactive site locations and structure-function study of the arrowhead
      proteinase inhibitors, A and B, using mutagenesis.
AB  - The arrowhead (Sagittaria sagittifolia, Linn.) proteinase inhibitor A and B are
      double-headed and multifunctional, consisting of 179 amino acid residues with
      three disulfide bridges. Both their primary structures and cDNA sequences have
      been elucidated [Yang, H. L., Luo, R. S., Wang, L. X., Zhu, D. X., & Chi, C. W.
      (1992) J. Biochem. 111, 537; Xu, W. F., Tao, W. K., Gong, Z. Z., & Chi, C. W.
      (1993) J. Biochem. 113, 153; Luo, M. J., Lu, W. Y., & Chi, C. W. (1997) J.
      Biochem. (in press)]. Though they share 91% homology, they are different in
      inhibitory activities. Sequence analysis of their full-length cDNAs showed that
      there are seven extra residues in the C-terminal part which might be cleaved off
      by proteinase post-processing. To locate the reactive sites and study the
      structure-function relationship of the two forms A and B, the genes coding for
      the mature inhibitor B and its extended form were respectively cloned into the
      secretion expression vector, pVT102U/alpha, and expressed in Saccharomyces
      cerevisiae strain S-78. Both of the gene products were purified and characterized
      to have the same inhibitory activities as the natural one. The gene product of
      the extended form was a mixture with the extended C-terminal part of the
      inhibitor either completely or partially removed. The two previously predicted
      reactive site residues, Lys-44 and Arg-76 of inhibitor B, were then respectively
      substituted with Ala by site-directed mutagenesis and expressed. As compared with
      the natural inhibitor, each of the mutants could only inhibit one molecule,
      instead of two molecules of trypsin, and displayed an inhibitory activity against
      elastase, thus confirming the location of the two reactive sites in the
      inhibitors. The gene coding for inhibitor A, which for some reason could not be
      expressed in S. cereviciae, was successfully expressed in the reconstructed
      plasmid pET-1522bx in Escherichia coli strain BL21 with the expressed product
      existing in the inclusion body. After denaturation and renaturation, the active
      inhibitor A was obtained and purified by anhydrotrypsin affinity chromatography.
      Using site-directed mutagenesis, two residues of inhibitor A, namely, Ser-82 and
      Leu-87, prominently different from Leu-82 and Arg-87 in inhibitor B, were
      replaced by these two corresponding residues, respectively. As compared with the
      natural inhibitor A, its S82L mutant showed a lower inhibitory activity toward
      trypsin, whereas a higher activity was found in the L87R mutant. Meanwhile, both
      of their chymotrypsin inhibitory activities became weaker than the natural one.
      The important accessary role of the residue of position 87 in causing the
      difference in inhibitory properties between inhibitor A and B was discussed.

PMID- 9153427
TI  - 17 alpha (haloacetamidoalkyl) estradiols alkylate the human estrogen receptor at
      cysteine residues 417 and 530.
AB  - Results obtained in a previous study suggested that cysteine residues in the
      estrogen receptor were covalent attachment sites for four 17 alpha
      (haloacetamidoalkyl) estradiols (halo, bromo or iodo; alkyl, methyl, ethyl, or
      propyl). To identify the putative concerned cysteines, we expressed wild-type and
      various cysteine --> alanine mutants of the human estrogen receptor in COS cells
      and determined their ability to be alkylated by the four electrophiles. The
      quadruple mutant, in which all the cysteines (residues 381, 417, 447, and 530) of
      the hormone-binding site were changed to alanines, showed very little
      electrophile labeling, whereas the four single mutants (C381A, C417A, C447A, and
      C530A) were alkylated as efficiently as the wild-type receptor. These results (i)
      demonstrate that cysteine residues were covalent attachment sites of
      electrophiles and (ii) indicate that more than one cysteine residue could be
      alkylated. Analysis of three double mutants (C381A/C530A, C417A/C530A, and
      C447A/C530A) provided strong evidence that only C417 and C530 were sites for
      electrophile covalent attachment. Since C530 was also alkylated by tamoxifen
      aziridine, a nonsteroidal affinity-labeling agent, we propose a selective mode of
      superimposition of tamoxifen-class antiestrogens with estradiol, which could
      account for the relative positioning of the two types of ligands in the receptor
      hormone-binding pocket. According to the structure of the hormone-binding pocket
      of nuclear receptors, as inferred from crystallographic studies and general
      sequence alignment of hormone-binding domains, C417 and C530 appear to be (1)
      located at the extreme border or in structural elements involved in delineation
      of the hormone-binding pocket, (2) spatially in close proximity to each other,
      and (3) in positions highly homologous to those of glucocorticoid receptor sites
      alkylated by affinity- and photoaffinity-labeling agents, respectively.

PMID- 9153426
TI  - Active site plasticity in D-amino acid oxidase: a crystallographic analysis.
AB  - D-Amino acid oxidase (DAAO) is the prototype of the flavin-containing oxidases.
      It catalyzes the oxidative deamination of various D-amino acids, ranging from D
      Ala to D-Trp. We have carried out the X-ray analysis of reduced DAAO in complex
      with the reaction product imino tryptophan (iTrp) and of the covalent adduct
      generated by the photoinduced reaction of the flavin with 3-methyl-2-oxobutyric
      acid (kVal). These structures were solved by combination of 8-fold density
      averaging and least-squares refinement techniques. The FAD redox state of DAAO
      crystals was assessed by single-crystal polarized absorption
      microspectrophotometry. iTrp binds to the reduced enzyme with the N, C alpha, C,
      and C beta atoms positioned 3.8 A from the re side of the flavin. The indole side
      chain points away from the cofactor and is bound in the active site through a
      rotation of Tyr224. This residue plays a crucial role in that it adapts its
      conformation to the size of the active site ligand, providing the enzyme with the
      plasticity required for binding a broad range of substrates. The iTrp binding
      mode is fully consistent with the proposal, inferred from the analysis of the
      native DAAO structure, that substrate oxidation occurs via direct hydride
      transfer from the C alpha to the flavin N5 atom. In this regard, it is remarkable
      that, even in the presence of the bulky iTrp ligand, the active center is made
      solvent inaccessible by loop 216-228. This loop is thought to switch between the
      "closed" conformation observed in the crystal structures and an "open" state
      required for substrate binding and product release. Loop closure is likely to
      have a role in catalysis by increasing the hydrophobicity of the active site,
      thus making the hydride transfer reaction more effective. Binding of kVal leads
      to keto acid decarboxylation and formation of a covalent bond between the keto
      acid C alpha and the flavin N5 atoms. Formation of this acyl adduct results in a
      nonplanar flavin, characterized by a 22 degrees angle between the pyrimidine and
      benzene rings. Thus, in addition to an adaptable substrate binding site, DAAO has
      the ability to bind a highly distorted cofactor. This ability is relevant for the
      enzyme's function as a highly efficient oxidase.

PMID- 9153428
TI  - Two COOH-terminal truncated cytoplasmic forms of topoisomerase II alpha in a VP
      16-selected lung cancer cell line result from partial gene deletion and
      alternative splicing.
AB  - Topoisomerase II alpha is a nuclear enzyme involved in chromosome segregation and
      other essential cellular processes. It is also the target of several clinically
      important antineoplastic agents such as the epipodophyllotoxin, VP-16
      (etoposide). We have previously described a VP-16-selected lung cancer cell line,
      H209/V6, that expresses reduced levels of two species of topoisomerase II alpha
      related mRNAs and a catalytically active, predominantly cytoplasmic topoisomerase
      II alpha-related protein that is 10 kDa smaller than the wild-type protein
      [Mirski, S. E. L., et al. (1993) Cancer Res. 53, 4866-4873; Feldhoff, P. W. et
      al. (1994) Cancer Res. 54, 756-762]. The smaller H209/V6 4.8 kb mRNA is missing
      988 nucleotides of contiguous coding and non-coding sequence at its 3' end
      resulting in an mRNA predicted to encode a truncated polypeptide missing three
      previously unrecognized potential COOH-proximal bipartite nuclear localization
      signals [Mirski, S. E. L., & Cole, S. P. C. (1995) Cancer Res. 55, 2129-2134]. We
      have now determined the structure of the larger 6.2 kb topoisomerase II alpha
      related mRNA and show that it is missing 684 nucleotides of contiguous 3' coding
      and non-coding sequence between nucleotide positions 4267 and 4951. This sequence
      is replaced by 847 nucleotides of new sequence, containing an in-frame stop codon
      after 41 nucleotides. The translation product of the 6.2 kb mRNA is predicted to
      contain 13 new amino acids replacing the COOH-terminal 109 residues of wild-type
      topoisomerase II alpha, producing a truncated polypeptide of approximately 160
      kDa. Immunoblot analyses using antisera against the unique COOH-terminal 13 and
      34 amino acids encoded by H209/V6 6.2 kb and 4.8 kb mRNAs, respectively,
      confirmed that both mRNAs are translated. Restriction enzyme analysis and
      sequencing of the 3'-proximal region of the TOP2A gene in the H209 and H209/V6
      DNA revealed that a partial deletion has occurred in H209/V6 and the novel
      sequence identified in the H209/V6 6.2 kb mRNA is derived from the adjacent 3'
      intron as a consequence of read-through at a concensus splice donor site. These
      observations suggest a mechanism for the generation of the two mutant
      topoisomerase II alpha mRNAs in H209/V6 cells and provide the first reported
      example of a drug resistant cell line containing two different cytoplasmic forms
      of topoisomerase II alpha.

PMID- 9153429
TI  - Gly-Gly-containing triplets of low stability adjacent to a type III collagen
      epitope.
AB  - Collagens, in addition to their structural role in the extracellular matrix,
      possess a number of functional binding domains. In this study, the binding to
      collagen of a monoclonal antibody is used as a model to define the molecular
      features involved in triple-helix interactions with other proteins. Here we
      report the thermal stability of an overlapping set of triple-helical peptides
      that includes the epitope recognized by a monoclonal antibody to type III
      collagen. Although the sequences of these peptides are very closely related, by a
      translation of a single triplet along the collagen chain, substantial variations
      in the melting temperatures were observed. These variations in thermal stability
      could not be readily explained by differences in imino acid content, or in
      numbers of charged or hydrophobic residues. The results indicate that Gly-Gly-Y
      triplets, which are adjacent to the epitope, have a strong influence in reducing
      the thermal stability of triple-helical peptides. Further studies, which were
      carried out on a set of "host-guest" triple-helical peptides containing different
      Gly-Gly-Y guest triplets, confirm the destabilizing effect of such tripeptides.
      The presence of Gly-Gly-Y triplets may play an important role in specific
      functions of type III collagen by modulating the local triple-helical structure
      or dynamics.

PMID- 9153430
TI  - A method for assessing the stability of a membrane protein.
AB  - The integral membrane protein diacylglycerol kinase (DGK) from Escherichia coli
      has been reversibly unfolded in a protein/detergent/mixed micelle system by
      varying the molar ratio of n-decyl beta-D-maltoside (DM) and sodium dodecyl
      sulfate (SDS). Unfolding was monitored by circular dichroism (CD) and ultraviolet
      (UV) absorbance spectroscopy. When unfolding is monitored by measuring changes in
      absorbance at 294 nm, two distinct denaturation phases are observed, indicative
      of a stable intermediate. When CD is used as a conformational probe, the
      resulting denaturation curve contains only one major transition, which
      corresponds to the first unfolding phase observed by absorbance changes. The
      unfolding behavior of several mutant proteins in which the tryptophan residues
      were selectively replaced made it possible to assign the first unfolding phase to
      a denaturation event in a cytoplasmic domain and the second phase to denaturation
      of the membrane-embedded portion of the protein. The denaturation curves fit well
      to a model which assumes two cooperative transitions and a linear relationship
      between unfolding free energy and SDS concentration. Extrapolation back to zero
      denaturant indicates an unfolding free energy of 6 kcal/mol for the cytoplasmic
      domain and 16 kcal/mol for the transmembrane domain. The high apparent stability
      of the transmembrane domain could explain the high degree of tolerance to amino
      acid substitutions seen for DGK and other membrane proteins. The approach
      described in this paper may be applicable to other membrane protein systems.

PMID- 9153431
TI  - Identification of the catalytic nucleophile of endoglucanase I from Fusarium
      oxysporum by mass spectrometry.
AB  - The endoglucanase EG I from Fusarium oxysporum catalyzes the hydrolysis of
      cellulose via a double-displacement mechanism involving the formation and
      hydrolysis of a glycosyl-enzyme intermediate. Treatment of EG I with 2',4'
      dinitrophenyl-2-deoxy-2-fluoro-beta-D-cellobioside results in the time-dependent
      inactivation of the enzyme (k(i) = 1.36 min(-1), Ki = 0.88 mM) via trapping of a
      covalent 2-deoxy-2-fluorocellobiosyl-enzyme intermediate. This intermediate is,
      however, catalytically competent undergoing transglycosylation, thus
      reactivation, in the presence of D-cellobiose. Analysis of a peptic digest of the
      inactivated enzyme by HPLC/ESMS/MS in the neutral loss mode allowed
      identification of a 2-fluorocellobiosyl-labeled peptide containing Glu197. This
      was confirmed by comparative mapping studies and subsequent Edman degradation
      analysis. This residue is completely conserved in glycosidase family 7, to which
      EG I belongs, consistent with its key role as the catalytic nucleophile.

PMID- 9153433
TI  - Spectral equilibration and primary photochemistry in Heliobacillus mobilis at
      cryogenic temperature.
AB  - We performed multicolor femtosecond transient absorption measurements on
      membranes of the photosynthetic bacterium Heliobacillus mobilis at 20 K, by
      selective excitation at either the red or the blue extreme of the
      bacteriochlorophyll g Q(Y) band, which is split in three spectral forms (Bchl g
      778, 793, and 808) at low temperature. In contrast to room temperature, there is
      no observable uphill energy transfer upon excitation at the red extreme. This
      provides a direct experimental confirmation of the expected strong temperature
      dependence of uphill energy transfer in multichromophore systems. Upon excitation
      at the blue edge, downhill energy transfer is observed on time ranges varying
      over 2 orders of magnitude and is discussed in terms of four distinct energy
      transfer processes: Bchl g 778* --> Bchl g 793* (approximately 50 fs); Bchl g
      778* --> Bchl g 808* (approximately 400 fs); Bchl g 793* --> Bchl g 808*
      (approximately 1.4 ps); and within Bchl g 808* (approximately 7 ps).
      Surprisingly, the amount of oxidized primary donor P798+ formed on the time scale
      of picoseconds and tens of picoseconds was found to depend on the excitation
      conditions: trapping occurs mainly in approximately 80 ps and slower from
      directly excited Bchl g 808* and can additionally occur in a few picoseconds from
      Bchl g 778* and Bchl g 793* upon blue excitation. This finding implies that
      spectral equilibration is not complete prior to charge separation and furthermore
      is inconsistent with a funnel model, in which P798 is surrounded by long
      wavelength pigments. More generally, we discuss to what extent our data bring
      constraints on the spatial distribution of the different spectral forms of the
      pigments.

PMID- 9153432
TI  - Structure of the endoglucanase I from Fusarium oxysporum: native, cellobiose, and
      3,4-epoxybutyl beta-D-cellobioside-inhibited forms, at 2.3 A resolution.
AB  - The mechanisms involved in the enzymatic degradation of cellulose are of great
      ecological and commercial importance. The breakdown of cellulose by fungal
      species is performed by a consortium of free enzymes, known as cellobiohydrolases
      and endoglucanases, which are found in many of the 57 glycosyl hydrolase
      families. The structure of the endoglucanase I (EG I), found in glycosyl
      hydrolase family 7, from the thermophilic fungus Fusarium oxysporum has been
      solved at 2.3 A resolution. In addition to the native enzyme, structures have
      also been determined with both the affinity label, 3,4-epoxybutyl beta-D
      cellobioside, and the reaction product cellobiose. The affinity label is
      covalently bound, as expected, to the catalytic nucleophile, Glu197, with clear
      evidence for binding of both the R and S stereoisomers. Cellobiose is found bound
      to the -2 and -1 subsites of the enzyme. In marked contrast to the structure of
      EG I with a nonhydrolyzable thiosaccharide analog, which spanned the -2, -1, and
      +1 subsites and which had a skew-boat conformation for the -1 subsite sugar
      [Sulzenbacher, G., et al. (1996) Biochemistry 35, 15280-15287], the cellobiose
      complex shows no pyranoside ring distortion in the -1 subsite, implying that
      strain is induced primarily by the additional +1 subsite interactions and that
      the product is found, as expected, in its unstrained conformation.

PMID- 9153434
TI  - Flavin mononucleotide-binding domain of the flavoprotein component of the sulfite
      reductase from Escherichia coli.
AB  - The flavoprotein component (SiR-FP) of the sulfite reductase from Escherichia
      coli is an octamer containing one FAD and one FMN as cofactors per polypeptide
      chain. We have constructed an expression vector containing the DNA fragment
      encoding for the FMN-binding domain of SiR-FP. The overexpressed protein (SiR
      FP23) was purified as a partially flavin-depleted polymer. It could incorporate
      FMN exclusively upon flavin reconstitution to reach a maximum flavin content of
      1.2 per polypeptide chain. Moreover, the protein could stabilize a neutral air
      stable semiquinone radical over a wide range of pHs. During photoreduction, the
      flavin radical accumulated first, followed by the fully reduced state. The redox
      potentials, determined at room temperature [E'1 (FMNH./FMN) = -130 +/- 10 mV and
      E'2 (FMNH2/FMNH.) = -335 +/- 10 mV], were very close to those previously reported
      for Salmonella typhimurium SiR-FP [Ostrowski, J., Barber, M. J., Rueger, D. C.,
      Miller, B. E., Siegel, L. M., & Kredich, N. M. (1989) J. Biol. Chem. 264, 15796
      15808]. Both the radical and fully reduced forms of SiR-FP23 were able to
      transfer their electrons to cytochrome c quantitatively. Altogether, the results
      presented herein demonstrate that the N-terminal end of E. coli SiR-FP forms the
      FMN-binding domain. It folds independently, thus retaining the chemical
      properties of the bound FMN, and provides a good model of the FAD-depleted form
      of native SiR-FP. Moreover, the FMN prosthetic group in SiR-FP23 and native SiR
      FP is compared to that of cytochrome P450 reductase and bacterial cytochrome
      P450, which also contain one FAD and one FMN per polypeptide chain.

PMID- 9153435
TI  - Research involving critically ill subjects in emergency circumstances: new
      regulations, new challenges.

PMID- 9153436
TI  - Butorphanol (Stadol): a study in problems of current drug information and
      control.
AB  - Butorphanol (Stadol, Bristol-Meyers Squibb, Princeton, NJ) is a synthetically
      derived opiate. As a nasal spray, it was approved for release in 1991 and was
      subsequently promoted as a safe treatment for migraine. Since then, there have
      been numerous reports of problems with butorphanol similar to those of any
      narcotic, especially dependence-addiction and major psychological disturbances.
      These problems have been documented by the Food and Drug Administration, but the
      information can be obtained only through the Freedom of Information Act. The
      experience with butorphanol indicates the need for physicians to have additional
      sources of information about drugs than are presently available.

PMID- 9153437
TI  - Psychiatric dizziness.

PMID- 9153438
TI  - Benign paroxysmal positioning vertigo: classic descriptions, origins of the
      provocative positioning technique, and conceptual developments.
AB  - The original description of benign paroxysmal positioning vertigo (BPPV) has been
      variously attributed to Barany, Adler, and others. In addition, the proper
      eponymic designation for the provocative positioning test used to diagnose BPPV
      has been unclear, because authors use a variety of different terms, including
      Barany, Nylen-Barany, Nylen, Hallpike, Hallpike-Dix, and Dix-Hallpike to refer to
      the procedure in current use. Based on a review of the extant medical literature,
      Barany was the first to describe the condition in detail, and Dix and Hallpike
      were the first to clearly describe both the currently used provocative
      positioning technique and the essential clinical manifestations of benign
      paroxysmal positioning vertigo elicited by that technique. Nevertheless, despite
      their important contributions, neither Barany nor Dix and Hallpike understood the
      pathophysiology of BPPV nor did they appreciate that the positioning techniques
      they used actually demonstrated pathology in the semicircular canals rather than
      the utricle. The modern understanding of the pathophysiology of BPPV began with
      Schuknecht's proposal that the dysfunction resulted from the gravity-dependent
      movement of loose or fixed dense material within the posterior semicircular canal
      ("cupulolithiasis"). Although Schuknecht's formulations were not consistent with
      all clinical features of the disease, they led to the modern "canalolithiasis
      theory" and highly effective canalith repositioning or "liberatory" maneuvers for
      BPPV.

PMID- 9153439
TI  - International Symposium for Therapy of Ocular Motility and Related Visual
      Disturbances.

PMID- 9153440
TI  - "Gourmand syndrome": eating passion associated with right anterior lesions.
AB  - We present a new benign eating disorder associated with lesions involving parts
      of the right anterior cerebral hemisphere. This "gourmand" syndrome describes a
      preoccupation with food and a preference for fine eating. Two exemplary case
      reports illustrate this new syndrome. Analysis of the clinical and anatomical
      data of 36 patients who displayed this behavior revealed, in 34, a strong
      association with lesion location in the right anterior part of the brain
      involving cortical areas, basal ganglia, or limbic structures. Our finding
      provides further evidence of a correlation between right hemispheric damage,
      eating, and other impulse control disorders. We conjecture that the serotonergic
      system subserves different functions in the left and right hemisphere.

PMID- 9153442
TI  - Pain after thalamic stroke: right diencephalic predominance and clinical features
      in 180 patients.
AB  - OBJECTIVE: To assess whether the thalamic pain syndrome of Dejerine-Roussy is
      produced preferentially by right diencephalic lesions and to elucidate its
      clinical features. BACKGROUND: Several experimental paradigms suggest that the
      right hemisphere is specialized for monitoring somatic states, including
      mediating pain. However, clinical studies of pain laterality have been
      inconclusive, possibly due to pathophysiologic diversity among analyzed patients.
      We collected reports of central pain laterality in a single, well-demarcated
      disorder, the Dejerine-Roussy syndrome. DESIGN/METHODS: Reports from English,
      French, and German literature were identified through Medline search and
      bibliography-guided retrieval. Inclusion criteria were (1) thalamic lesion
      documented by CT, MRI, or postmortem examination and (2) contralateral pain.
      Exclusion criteria were (1) tumoral/nonvascular etiology (to optimize anatomic
      localization), (2) symptoms consisting solely of evoked dysesthesia without
      spontaneous pain, or (3) sidedness of lesion not clearly indicated. Cases were
      analyzed for laterality as well as secondary anatomic and clinical variables.
      RESULTS: Literature search identified 274 cases. After exclusions, 180 remained.
      A total of 114 had a right-sided thalamic lesion, 66 left-sided (p < 0.001).
      Laterality predominance was greater among men than women. The frequency of other
      components of the Dejerine-Roussy syndrome--sensory impairment, hemiparesis,
      ataxia, and choreoathetosis--did not significantly differ between right and left
      groups. Pain onset was within the first week poststroke in 36%. Frequency of
      spontaneous pain was 14% after any thalamic stroke and 24% after geniculothalamic
      artery territory stroke. CONCLUSION: Right-sided lesions predominate among
      reported cases of the thalamic pain syndrome. This preferential involvement of
      the nondominant thalamus in pain processing is supportive evidence of a
      nondominant hemisphere specialization in monitoring somatic states.

PMID- 9153441
TI  - A population-based study of prognosis of ruptured cerebral aneurysm: mortality
      and recurrence of subarachnoid hemorrhage.
AB  - OBJECTIVE: To determine the risk of recurrent subarachnoid hemorrhage (SAH),
      mortality, and relative survivorship following SAH caused by ruptured cerebral
      aneurysm (RCA). DESIGN/METHODS: The 86 individuals with a first diagnosis of SAH
      caused by RCA in Iceland from 1958 through 1968 were followed a minimum of 24
      years (range, 24 to 32.5 years) or until death to determine mortality and to
      identify those with recurrent SAH. RESULTS: Thirty-eight patients (44%) died
      within 30 days of the index event. Two additional (both comatose from onset of
      ictus) died in the following month. There were no deaths between 3 and 6 months
      after onset. Based upon the age/gender-specific person years of observation for
      the population of Iceland, the Standardized Mortality Ratio for the 44 surgically
      treated patients surviving 6 months was 1.3. Those neurologically normal or with
      only mild impairment at 6 months had no identified increase in mortality. Excess
      mortality that was limited to individuals with severe neurologic deficit at 6
      months could be identified through the first 10 years after onset. Two 6-month
      survivors experienced recurrent SAH. CONCLUSIONS: Early mortality is high (47%)
      in patients with RCA. In patients operated on for RCA and surviving 6 months,
      recurrent SAH occurred in 5%. Survivorship among patients surgically treated and
      neurologically normal or with mild residual neurologic impairment at 6 months
      following presentation was similar to that expected in the general population.
      Survivorship among patients surgically treated who had severe residual neurologic
      impairment at 6 months was significantly reduced.

PMID- 9153443
TI  - Unusual clinical features and early brain MRI lesions in a family with cerebral
      autosomal dominant arteriopathy.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is a recently described inherited disorder. The
      pathologic gene maps on chromosome 19. The clinical spectrum of the disease
      consists of recurrent strokes, migraine, transient ischemic attacks, mood
      changes, and dementia. We report a genetically assessed CADASIL family with
      atypical clinical presentations of epileptic seizures. In two asymptomatic family
      members there were early brain abnormalities on MRI. Our report expands the
      clinical spectrum of CADASIL and suggests that it is possibly an undiagnosed
      disorder.

PMID- 9153444
TI  - Testing the validity of the lacunar hypothesis: the Northern Manhattan Stroke
      Study experience.
AB  - BACKGROUND/OBJECTIVE: Few studies have attempted to validate the "lacunar
      hypothesis." The accuracy of identifying lacunar and other nonlacunar mechanisms
      of infarction will be increasingly important in evaluating potential stroke
      treatments. The aim of this study was to determine the value of lacunar syndromes
      in predicting radiologic lacunes and the value of clinicoradiologic lacunes in
      predicting "lacunar infarction" as final stroke mechanism. METHODS: From 1990 to
      1994, 591 patients with cerebral infarction, who were from northern Manhattan and
      over the age of 39, were prospectively examined. Data were collected on the
      admitting clinical syndrome (lacunar or nonlacunar) and brain imaging findings.
      Lacunar syndromes were categorized as pure motor hemiparesis (PMH), pure sensory
      syndrome (PSS), sensorimotor syndrome (SMS), ataxic-hemiparesis (A-H), and other
      lacunar syndromes. Brain imaging findings were classified as radiologic lacune or
      nonlacune. Positive predictive values, sensitivities, and specificities of
      lacunar syndromes for identifying radiologic lacunes were calculated. The final
      mechanism of infarction was determined after review of all the diagnostic tests
      and compared among the lacunar groups. RESULTS: Lacunar syndromes occurred in 225
      cases. PMH was the most common lacunar syndrome, accounting for 45%, SMS 20%, A-H
      18%, and PSS 7%. Lacunar syndromes had an overall positive predictive value (PPV)
      of 87% for detecting radiologic lacune: PSS 100%, A-H 95%, SMS 87%, and PMH 79%.
      Among the 195 patients who presented with a lacunar syndrome and had this
      condition confirmed radiologically, 147 were classified as having a final
      diagnosis of lacunar mechanism of infarction (PPV = 75%). Atherosclerosis
      accounted for 17 (9%), cardioembolism 10 (5%), cryptogenic 17 (9%), and other
      unusual causes 4 (2%). CONCLUSION: While lacunar syndromes, especially PSS and A
      H, are highly predictive of lacune, in about one in four patients presenting with
      lacunar syndromes confirmed radiologically the condition is associated with
      nonlacunar mechanisms of infarction. Noninvasive neurovascular and cardiac
      evaluations are still warranted even among patients with lacunes.

PMID- 9153445
TI  - High-dose oral dextromethorphan versus placebo in painful diabetic neuropathy and
      postherpetic neuralgia.
AB  - N-methyl-D-aspartate (NMDA) receptor antagonists relieve neuropathic pain in
      animal models, but side effects of dissociative anesthetic channel blockers, such
      as ketamine, have discouraged clinical application. Based on the hypothesis that
      low-affinity NMDA channel blockers might have a better therapeutic ratio, we
      carried out two randomized, double-blind, crossover trials comparing six weeks of
      oral dextromethorphan to placebo in two groups, made up of 14 patients with
      painful distal symmetrical diabetic neuropathy and 18 with postherpetic
      neuralgia. Thirteen patients with each diagnosis completed the comparison. Dosage
      was titrated in each patient to the highest level reached without disrupting
      normal activities; mean doses were 381 mg/day in diabetics and 439 mg/day in
      postherpetic neuralgia patients. In diabetic neuropathy, dextromethorphan
      decreased pain by a mean of 24% (95% CI: 6% to 42%, p = 0.01), relative to
      placebo. In postherpetic neuralgia, dextromethorphan did not reduce pain (95% CI:
      10% decrease in pain to 14% increase in pain, p = 0.72). Five of 31 patients who
      took dextromethorphan dropped out due to sedation or ataxia during dose
      escalation, but the remaining patients all reached a reasonably well-tolerated
      maintenance dose. We conclude that dextromethorphan or other low-affinity NMDA
      channel blockers may have promise in the treatment of painful diabetic
      neuropathy.

PMID- 9153446
TI  - Magnetic resonance imaging of the brachial plexus in patients with multifocal
      motor neuropathy.
AB  - We studied whether magnetic resonance (MR) imaging of the brachial plexus is
      useful to distinguish multifocal motor neuropathy (MMN) from lower motor neuron
      disease (LMND) and whether abnormalities resemble those of chronic inflammatory
      demyelinating polyradiculoneuropathy (CIDP). We compared MR images of the
      brachial plexus of nine patients with MMN with scans from five patients with
      CIDP, eight patients with LMND, and 174 controls. In two patients with MMN, and
      in three patients with CIDP, the MR images showed an increased signal intensity
      on the T2-weighted images of the brachial plexus. Two other patients with MMN
      demonstrated a more focal, increased signal intensity on the T2-weighted images,
      occurring in one patient only in the axilla, and in the other patient in the
      axilla and in the ventral rami of the roots. MR images of the brachial plexus of
      eight patients with LMND were normal. The distribution of the MR imaging
      abnormalities corresponded with the distribution of symptoms of the patients:
      asymmetrical in MMN and symmetrical in CIDP. These findings demonstrate that MR
      imaging abnormalities of the brachial plexus in patients with MMN resemble those
      seen in CIDP and may be useful to distinguish MMN from LMND.

PMID- 9153447
TI  - A beneficial effect of oxandrolone in the treatment of Duchenne muscular
      dystrophy: a pilot study.
AB  - We treated 10 boys with Duchenne muscular dystrophy with oxandrolone, an anabolic
      steroid, for 3 months. The mean of the changes in the average muscle score was an
      improvement of 0.315 +/- 0.097. The expected mean change in muscle score after 3
      months from natural history data is a loss of 0.1. The difference of 0.415
      between the actual and expected values is significant at p < 0.01. This
      preliminary evidence suggests that oxandrolone treatment may provide a degree of
      functional benefit for children with Duchenne muscular dystrophy that is similar
      to that after prednisone administration.

PMID- 9153448
TI  - Primary adhalinopathy (alpha-sarcoglycanopathy): clinical, pathologic, and
      genetic correlation in 20 patients with autosomal recessive muscular dystrophy.
AB  - Primary adhalin (or alpha-sarcoglycan) deficiency due to a defect of the adhalin
      gene localized on chromosome 17q21 causes an autosomal recessive myopathy. We
      evaluated 20 patients from 15 families (12 from Europe and three from North
      Africa) with a primary adhalin deficiency with two objectives: characterization
      of the clinical phenotype and analysis of the correlation with the level of
      adhalin expression and the type of gene mutation. Age at onset and severity of
      the myopathy were heterogeneous: six patients were wheel-chair bound before 15
      years of age, whereas five other patients had mild disease with preserved
      ambulation in adulthood. The clinical pattern was similar in all the patients
      with symmetric characteristic involvement of trunk and limb muscles, calf
      hypertrophy, and absence of cardiac dysfunction. Immunofluorescence and
      immunoblot studies of muscle biopsy specimens showed a large variation in the
      expression of adhalin. The degree of adhalin deficiency was fairly correlated
      with the clinical severity. There were 15 different mutations (10 missense, five
      null). Double null mutations (three patients) were associated with severe
      myopathy, but in the other cases (null/missense and double missense) there was a
      large variation in the severity of the disease.

PMID- 9153449
TI  - Steroid myopathy in cancer patients.
AB  - We prospectively evaluated 15 adult cancer patients being treated with
      adrenocorticosteroids (steroids) to determine the frequency and time course of
      "steroid myopathy." Nine (60%) developed clinically detectable proximal muscle
      weakness that, in six, was severe enough to interfere with activities of daily
      living. Proximal muscle weakness developed within 15 days in eight of nine
      patients and was significantly related to the cumulative dose of steroid. Eight
      of nine patients with proximal muscle weakness, and two of six without such
      weakness, experienced a significant decline in respiratory function, leading to
      symptomatic dyspnea in four patients of the former group. In three patients who
      could be followed for more than 3 months off steroids, there was either
      improvement or resolution of the weakness and, when present, of the respiratory
      impairment. Steroid myopathy is a common complication among cancer patients
      receiving steroids. It can often affect respiratory function even when proximal
      limb muscles remain strong. Clinical recognition is important since steroid
      myopathy can lead to increased morbidity and may be reversible with reduction or
      discontinuation of steroids.

PMID- 9153450
TI  - Mitochondrial encephalomyopathy with coenzyme Q10 deficiency.
AB  - Coenzyme Q10 (CoQ10) transfers electrons from complexes I and II of the
      mitochondrial respiratory chain to complex III. There is one published report of
      human CoQ10 deficiency describing two sisters with encephalopathy, proximal
      weakness, myoglobinuria, and lactic acidosis. We report a patient who had delayed
      motor milestones, proximal weakness, premature exertional fatigue, and episodes
      of exercise-induced pigmenturia. She also developed partial-complex seizures.
      Serum creatine kinase was approximately four times the upper limit of normal and
      venous lactate was mildly elevated. Skeletal muscle biopsy revealed many ragged
      red fibers, cytochrome c oxidase-deficient fibers, and excess lipid. In isolated
      muscle mitochondria, impaired oxygen consumption was corrected by the addition of
      decylubiquinone. During standardized exercise, ventilatory and circulatory
      responses were compatible with a defect of oxidation-phosphorylation, which was
      confirmed by near-infrared spectroscopy analysis. Biochemical analysis of muscle
      extracts revealed decreased activities of complexes I+II and I+III, while CoQ10
      concentration was less than 25% of normal. With a brief course of CoQ10 (150 mg
      daily), the patient reported subjective improvement. The triad of CNS
      involvement, recurrent myoglobinuria, and ragged-red fibers should alert
      clinicians to the possibility of CoQ10 deficiency.

PMID- 9153451
TI  - Autosomal dominant progressive external ophthalmoplegia with multiple deletions
      of mtDNA: clinical, biochemical, and molecular genetic features of the 10q-linked
      disease.
AB  - Autosomal dominant progressive external ophthalmoplegia (adPEO) is a
      mitochondrial disease characterized by accumulation of multiple large deletions
      of mtDNA in patients' tissues. We previously showed that the disease is
      genetically heterogeneous by assigning two nuclear loci predisposing to mtDNA
      deletions: one on chromosome 10q 23.3-24.3 in a Finnish family and one on 3p 14.1
      21.2 in three Italian families. To reveal any locus-specific disease features, we
      report here the clinical, biochemical, and molecular genetic characteristics of
      the 10q-linked disease in the single family reported to date. All seven patients
      and four asymptomatic subjects had ragged-red fibers and multiple deletions of
      mtDNA in their muscle. Ptosis and external ophthalmoplegia were the major
      clinical findings, and depression or avoidant personality traits were frequently,
      but not consistently, present in the subjects carrying mutant mtDNA. In six of
      the subjects with mutant mtDNA, the activities of the respiratory chain complexes
      I or IV, or both, were below or within the low normal range. Two autopsy studies
      revealed the characteristic distribution of mutant mtDNA in these patients:
      highest proportion of mutant mtDNA is found in different parts of the brain,
      followed by the skeletal and ocular muscle, and the heart.

PMID- 9153452
TI  - Myasthenic crisis: clinical features, mortality, complications, and risk factors
      for prolonged intubation.
AB  - We retrospectively reviewed the hospital records of 53 patients admitted for 73
      episodes of myasthenic crisis at Columbia-Presbyterian Medical Center over a
      period of 12 years, from 1983 to 1994. Median age at the onset of first crisis
      was 55 (range, 20 to 82), the ratio of women to men was 2:1, and the median
      interval from onset of symptoms to first crisis was 8 months. Infection (usually
      pneumonia or upper respiratory infection) was the most common precipitating
      factor (38%), followed by no obvious cause (30%) and aspiration (10%). Twenty
      five percent of patients were extubated at 7 days, 50% at 13 days, and 75% at 31
      days; the longest crisis exceeded 5 months. Using survival analysis and backward
      stepwise Cox regression, we identified three independent predictors of prolonged
      intubation: (1) pre-intubation serum bicarbonate > or = 30 mg/dl (p = 0.0004,
      relative hazard 4.5), (2) peak vital capacity day 1 to 6 post-intubation < 25
      ml/kg (p = 0.001, relative hazard 2.9), and (3) age > 50 (p = 0.01, relative
      hazard 2.4). The proportion of patients intubated longer than 2 weeks was 0%
      among those with no risk factors, 21% with one risk factor, 46% with two risk
      factors, and 88% with three risk factors (p = 0.0004). Complications
      independently associated with prolonged intubation included atelectasis (p =
      0.002), anemia treated with transfusion (p = 0.03), Clostridium difficile
      infection (p = 0.01), and congestive heart failure (p = 0.03). Three episodes of
      crisis were fatal, for a mortality rate of 4% (3/73); four additional patients
      died after extubation. All seven deaths were due to overwhelming medical
      comorbidity. Over half of those who survived were functionally dependent (home or
      institutionalized) at discharge. In addition to prospective controlled studies of
      immunotherapies, the prevention and treatment of medical complications offers the
      best opportunity for further improving the outcome of myasthenic crisis.

PMID- 9153453
TI  - Antibodies to synthetic peptides of the alpha1A subunit of the voltage-gated
      calcium channel in Lambert-Eaton myasthenic syndrome.
AB  - To search for antigenic sites in the molecular structure of alpha1A subunit of
      the voltage-gated calcium channel (VGCC) (P/Q-type) in the Lambert-Eaton
      myasthenic syndrome (LEMS), we studied by immunoprecipitation assay serum samples
      from 30 LEMS patients (16 with small cell lung carcinoma (SCLC), 20 disease
      controls (10 with SCLC without LEMS and 10 with myasthenia gravis), and 15
      healthy controls. Synthetic peptide antigens corresponded to the extracellular
      region (S5-S6 linker region) of each of the four domains forming the alpha1
      subunit of P/Q-type VGCC. In addition, we studied serum samples for anti-P/Q-type
      VGCC antibodies by using omega-conotoxin MVIIC-labeled extract of human
      cerebellum as an antigen. Among sera of 30 LEMS patients, nine samples (30%) (six
      with SCLC) were positive for antibodies to the domain IV S5-S6 linker peptide,
      and six samples (20%) (five with SCLC) were positive for antibodies to the domain
      II S5-S6 linker peptide. Only two of 15 antipeptide-positive sera were positive
      for both antibodies. Titers for antibodies to domain IV, as well as those for
      antibodies to domain II, correlated with those of anti-P/Q-type VGCC (human
      cerebellum extract) antibodies. The antipeptide antibody was present in only one
      of 20 disease controls, a patient with SCLC without LEMS. Our observations
      suggest two potential epitopes of LEMS antibodies.

PMID- 9153455
TI  - Increased CSF glutamate following injection of ALS immunoglobulins.
AB  - To reconcile the autoimmune and excitotoxic hypotheses regarding the etiology of
      amyotrophic lateral sclerosis (ALS), we injected rats intraperitoneally with ALS
      immunoglobulins and monitored CSF glutamate, aspartate, glutamine, and
      glutathione. CSF glutamate was significantly increased at 24 and 72 hours
      compared with both basal levels and disease control injected rats. CSF aspartate
      was increased at 72 hours. Glutamine and glutathione were unchanged. These data
      suggest that ALS immunoglobulins may enhance CSF glutamate and aspartate levels
      and contribute to motoneuron injury.

PMID- 9153454
TI  - Decreased expression of full-length mRNA for cBCD541 does not correlate with
      spinal muscular atrophy phenotype severity.
AB  - Spinal muscular atrophy (SMA) is characterized by degeneration of spinal cord
      anterior horn cells and muscular atrophy and has three phenotypes based on
      clinical severity and age of onset. One of the responsible genes for SMA is the
      survival motor neuron (SMN) gene, which is homozygously absent or interrupted in
      more than 90% of SMA patients. The cBCD541 (BCD) gene is a highly homologous copy
      of the SMN gene, which has a single synonymous transition in the coding region
      and may compensate for the loss of the SMN gene. To evaluate the effects of the
      BCD gene expression on the phenotypes of SMA, we examined lymphocyte mRNA from 9
      SMA patients lacking the SMN gene, 10 asymptomatic parents, and 15 control
      subjects. We amplified mRNA fragments containing exon 7 of the SMN or BCD genes
      using reverse transcription-polymerase chain reaction since the transcript
      lacking exon 7 encodes a putative protein with a different C-terminal end. We
      used glyceraldehyde-3-phosphate dehydrogenase (GAPDH) transcript as an internal
      control, and the relative expression level of the SMN or BCD gene was shown as
      the ratio of SMN or BCD transcript to GAPDH transcript (S/G ratio). The mean S/G
      ratios of the patients were significantly lower than that of the parents and
      controls. However, among the patients examined in this study, there was no
      relationship between the S/G ratios and phenotypes of SMA. The results showed
      that the BCD gene expression was not related to the phenotypes of SMA.
      Furthermore, there was an overlap between the S/G ratios in patients and
      controls. As our discrimination study showed that the S/G ratio reflected the
      expression of the BCD transcripts in patients and the SMN transcripts in
      controls, this finding suggested that the BCD gene expression per se does not
      compensate for the loss of the SMN gene.

PMID- 9153456
TI  - Stereotactic pallidotomy for Parkinson's disease: a long-term follow-up of
      unilateral pallidotomy.
AB  - Eleven patients suffering from Parkinson's disease were followed for up to 4
      years after unilateral pallidotomy. We observed persistent contralateral
      improvement and unexpected ipsilateral improvement of motor symptoms. In
      addition, there was a protracted relief of contralateral dyskinesias and
      maintenance of relatively stable levodopa dosage.

PMID- 9153457
TI  - A population perspective on diagnostic criteria for Parkinson's disease.
AB  - For Parkinson's disease (PD), little is known about how the choice of diagnostic
      criteria affects research results. Using data on PD from three community studies
      (from Argentina, the Netherlands, Italy), we compared the impact on prevalence of
      several sets of diagnostic criteria. Each set was based on cardinal signs-
      resting tremor, bradykinesia, rigidity, impaired postural reflexes--and required
      that other parkinsonism be excluded. Some sets had additional requirements
      related to duration of symptoms, asymmetry of signs, or response to medication.
      In terms of prevalence, much lower estimates were associated with the
      requirements of asymmetry of signs and response to medication. The assessment of
      these clinical features may not be practical in community studies. Impaired
      postural reflexes, as a cardinal sign, seemed superfluous. For community studies
      of PD, we recommend the following diagnostic criteria: at least two of resting
      tremor, bradykinesia, or rigidity, in the absence of other apparent causes of
      parkinsonism.

PMID- 9153458
TI  - Lamotrigine trial in idiopathic parkinsonism: a double-blind, placebo-controlled,
      crossover study.
AB  - Increased glutamatergic transmission in the basal ganglia is implicated in the
      pathophysiology of idiopathic parkinsonism (IP). We investigated the effects of
      lamotrigine (LTG), a glutamate-release inhibitor, in the symptomatic treatment of
      IP in two double-blind, placebo-controlled studies. Single doses of L
      dopa/carbidopa (equal to 50% of the usual morning dose) were administered
      together with either LTG (100, 200, or 400 mg) or two random placebo doses in 14
      patients with IP. The patients were assessed using the Modified Columbia Rating
      Scale (MCRS) and the Purdue Pegboard Test (PPBT) at multiple intervals over 8
      hours. There were no significant differences between the placebo doses and the
      three doses of LTG on the MCRS and PPBT scores. In a 3-month study, 12 patients
      took LTG titrated up to 400 mg or placebo with their antiparkinsonian medication
      for 3 months and were then crossed over. Nine of 12 patients did not complete the
      study because of dyskinesia (n = 2), hallucinations (n = 3), and deterioration of
      parkinsonian symptoms (n = 4) on LTG. There was no significant difference between
      placebo and LTG on the MCRS and PPBT in the three patients who completed the
      study. The results failed to demonstrate any symptomatically beneficial effects
      of LTG in IP.

PMID- 9153459
TI  - Atypical parkinsonism in a family of Portuguese ancestry: absence of CAG repeat
      expansion in the MJD1 gene.
AB  - We studied the clinical features and molecular genetics of a family, afflicted
      with a form of atypical parkinsonism, originating from the Madeira Islands of
      Portugal. We examined four affected individuals and reviewed clinical information
      on one other affected family member. Mean age at onset was 31 years. Parkinsonism
      (akinesia, rigidity, gait disturbance) was the most prominent feature in advanced
      disease. Levodopa responsiveness with peak-dose dyskinesia was present in one
      individual. Initial symptoms and other clinical features were variable and
      included other extrapyramidal signs (dystonia, action tremor of the limbs and
      bulbar muscles, synkinesis), ophthalmologic abnormalities (ptosis, slow saccades,
      progressive external ophthalmoplegia, hypometric saccades, saccadic pursuit
      movements), speech abnormalities (dysarthria, hypernasality), cortical impairment
      (dementia, frontal lobe dysfunction, palilalia, perseveration), minor cerebellar
      signs (dysmetria, gait ataxia), pyramidal abnormalities (spasticity,
      hyperreflexia), and peripheral nervous system abnormalities (propioceptive loss,
      areflexia, distal weakness, atrophy). The length of trinucleotide repeats in the
      MJD1 gene was in the normal range for all affected individuals.

PMID- 9153461
TI  - Volume loss of the hippocampus and temporal lobe in healthy elderly persons
      destined to develop dementia.
AB  - OBJECTIVE: To determine initial locus and rate of degeneration of temporal lobe
      structures (total lobe, hippocampus and parahippocampus) in preclinical dementia.
      BACKGROUND: Postmortem studies suggest that the earliest changes in Alzheimer's
      disease are neurofibrillary tangle formation in hippocampus and adjacent cortex.
      MRI volume analysis of temporal lobe structures over time in subjects prior to
      developing dementia may allow the identification of when these processes begin,
      the rate they develop, and which areas are key to symptom development. METHODS:
      30 nondemented (NoD), healthy, elderly individuals enrolled in a prospective
      study of healthy aging evaluated annually over a mean of 42 months. Twelve
      subjects with subsequent cognitive decline were assigned to the preclinical
      dementia group (PreD). All 120 annual MRI studies analyzed by volumetric
      techniques assessed group differences in temporal lobe volumes and rates of brain
      loss. RESULTS: NoD as well as PreD subjects had significant, time-dependent
      decreases in hippocampal and parahippocampal volume. Rates of volume loss between
      the groups did not significantly differ. PreD cases had significantly smaller
      hippocampi when asymptomatic. Parahippocampal volume did not differ between PreD
      and NoD cases. Significant time-dependent temporal lobe atrophy was present only
      in PreD. CONCLUSIONS: Hippocampal and parahippocampal atrophy occurs at a similar
      rate regardless of diagnostic group. Those who develop dementia may have smaller
      hippocampi to begin with, but become symptomatic because of accelerated loss of
      temporal lobe volume. Temporal lobe volume loss may mark the beginning of the
      disease process within six years prior to dementia onset.

PMID- 9153460
TI  - Oral phenylalanine loading in dopa-responsive dystonia: a possible diagnostic
      test.
AB  - To determine if there is abnormal phenylalanine and biopterin metabolism in
      patients with dopa-responsive dystonia (DRD), we measured plasma levels of
      phenylalanine, tyrosine, biopterin, and neopterin at baseline, and 1, 2, 4, and 6
      hours after an oral phenylalanine load (100 mg/kg). Seven adults with DRD, two
      severely affected children with DRD, and nine adult controls were studied. All
      patients had phenylalanine and tyrosine concentrations within the normal range at
      baseline. In the adult patients, phenylalanine levels were higher than in
      controls at 2, 4, and 6 hours post-load (p < 0.0005); tyrosine concentrations
      were lower than control levels at 1, 2, and 4 hours post-load (p < 0.05).
      Phenylalanine to tyrosine ratios were elevated in patients at all times post-load
      (p < 0.0005). Biopterin levels in the patients were decreased at baseline and 1,
      2, and 4 hours post-load (p < 0.005). Pretreatment with tetrahydrobiopterin (7.5
      mg/kg) normalized phenylalanine and tyrosine profiles in two adult patients. In
      the children with DRD, phenylalanine to tyrosine ratios were slightly elevated at
      baseline. Following phenylalanine loading, the phenylalanine profiles were
      similar to those seen in the adult patients but there was no elevation in plasma
      tyrosine. Baseline biopterin levels were lower in the children with DRD than in
      the adult patients or the controls and there was no increase in biopterin post
      load. In both the children and adults with DRD, neopterin concentrations did not
      differ from control values at baseline or after phenylalanine load. The results
      are consistent with decreased liver phenylalanine hydroxylase activity due to
      defective synthesis of tetrahydrobiopterin in patients with DRD. The findings
      show that a phenylalanine load may be useful in the diagnosis of this disorder.

PMID- 9153462
TI  - Predictors of time to institutionalization of patients with Alzheimer's disease:
      the CERAD experience, part XVII.
AB  - We studied the time to institutionalization (or death as the first event) in 727
      white patients with Alzheimer's disease (AD) enrolled in the Consortium to
      Establish a Registry for Alzheimer's disease (CERAD). At the time of analysis,
      417 patients had been admitted to nursing homes and 32 others had died without
      previous institutionalization. The major predictors of time to first event were
      sex, age, marital status (men only), and severity of dementia at entry into the
      study, as measured by activities of daily living, the Mini-Mental State
      Examination, and the Clinical Dementia Rating scale. The overall median time from
      enrollment in the study to first event was 3.1 years. For unmarried men, the
      median time was significantly less (2.1 years) than for either married men or for
      married or unmarried women, all of whom had medians greater than 3 years. In an
      analysis of survival time following institutionalization, we found that men
      survived a median of 2.1 years, compared with 4.5 years for women. This
      nationwide study of AD largely confirms earlier studies that reported on smaller
      numbers of cases from local catchment areas and included patients with various
      types of dementia.

PMID- 9153463
TI  - Widespread dilatation of perivascular spaces: a leukoencephalopathy causing
      dementia.
AB  - A 68-year-old demented woman had widespread dilatation of perivascular spaces in
      the cerebral white matter for at least 12 years. There were no micro-infarcts,
      but some vessel walls in the white matter were thickened by a loose fibrosis. Our
      case does not correspond to Binswanger's disease or any other known vascular
      leukoencephalopathy. The longstanding evolution points to a nonfamilial
      leukoencephalopathy of probable vascular origin.

PMID- 9153464
TI  - No association between the alpha 1-antichymotrypsin A allele and Alzheimer's
      disease.
AB  - The alpha 1-antichymotrypsin (ACT) A allele was recently associated with
      Alzheimer's disease (AD), and the ACT AA genotype was reported to be more
      frequent in AD subjects with the apolipoprotein E (APOE) epsilon4 allele. We
      examined ACT and APOE genotypes in a sample of 160 subjects with probable AD and
      in 102 elderly control subjects. ACT A allele frequencies were similar in AD
      subjects (0.503) and elderly controls (0.519). In addition, we found no evidence
      that in AD the AA genotype is more frequent in subjects with the APOE epsilon4
      allele than in those without it. Our results do not support an association
      between the ACT A allele and AD.

PMID- 9153465
TI  - Dementia after stroke increases the risk of long-term stroke recurrence.
AB  - BACKGROUND: Although risk factors for first stroke have been identified, the
      predictors of long-term stroke recurrence are less well understood. We performed
      the present study to determine whether dementia diagnosed three months after
      stroke onset is an independent risk factor for long-term stroke recurrence.
      METHODS: We examined 242 patients (age = 72.0 +/- 8.7 years) hospitalized with
      acute ischemic stroke who had survived the first three months without recurrence
      and followed them to identify predictors of long-term stroke recurrence. We
      diagnosed dementia three months after stroke using modified DSM-III-R criteria
      based on neuropsychological and functional assessments. The effects of
      conventional stroke risk factors and dementia status on survival free of
      recurrence were estimated using Kaplan-Meier analyses, and the relative risks
      (RR) of recurrence were calculated using Cox proportional hazards models.
      RESULTS: Dementia (RR = 2.71, 95% CI = 1.36 to 5.42); cardiac disease (RR = 2.18,
      CI = 1.15 to 4.12); and sex, with women at higher risk (RR = 2.03, CI = 1.01 to
      4.10), were significant independent predictors of recurrence, while education (RR
      = 1.90, CI = 0.77 to 4.68), admission systolic blood pressure >160 mm Hg (RR =
      1.80, CI = 0.94 to 3.44) and alcohol intake exceeding 160 grams per week (RR =
      1.86, CI = 0.79 to 4.38) were weakly related. CONCLUSIONS: Our results suggest
      that dementia significantly increases the risk of long-term stroke recurrence,
      with additional independent contributions by cardiac disease and sex. Cognitive
      impairment may be a surrogate marker for multiple vascular risk factors and
      larger infarct volume that may serve to increase the risk of recurrence.
      Alternatively, less aggressive medical management of stroke patients with
      cognitive impairment or noncompliance of such patients with medical therapy may
      be bases for an increased rate of stroke recurrence.

PMID- 9153466
TI  - 99mTc-SPECT in the diagnosis of skull base metastasis.
AB  - OBJECTIVE: To evaluate the role of bone SPECT in diagnosing metastasis to the
      skull base in cancer patients. BACKGROUND: Skull base metastasis often causes
      characteristic clinical syndromes. Antitumor treatment ameliorates or stabilizes
      symptoms in most patients. Diagnosis may be difficult when neuroimaging studies
      are negative (as occurs in about one-quarter of patients). Case reports have
      suggested a role for bone SPECT in these patients. METHODS: We reviewed the
      charts of all patients (1993-1996) at our institution who had skull base SPECT
      and at least one neuroimaging study (CT or MRI) for clinically suspected
      metastasis to the base of the skull. Bone SPECT, CT, and MRI were blindly re
      evaluated. RESULTS: We studied 56 patients, of whom 36 had skull base metastasis.
      Twenty patients had other causes of the clinical syndrome, including
      leptomeningeal and posterior fossa metastasis, or benign causes. In 29 of 36
      patients (81%) with skull base metastasis, CT or MRI clearly demonstrated the
      lesion. Bone SPECT identified a hot spot in the appropriate region of the skull
      base in 28 of 36 patients (78%). All seven patients with negative CT or MRI had
      positive SPECT and four of these had a response to anti-tumor treatment.
      CONCLUSIONS: SPECT of the skull base can demonstrate lesions not identifiable by
      CT or MRI. In cancer patients suspected of having skull base metastasis, we
      recommend SPECT of the skull base when CT or MRI studies are negative.

PMID- 9153467
TI  - Concurrence of multiple sclerosis and brain tumor: clinical considerations.
AB  - We report a patient with multiple sclerosis (MS) who developed an
      oligodendroglioma 8 years after the initial diagnosis of MS. This is the first
      description of a neoplasm, suspected initially on brain MRI and subsequently
      confirmed by brain biopsy, in an MS patient. Our case emphasizes the need to
      evaluate atypical brain MRI lesions carefully, even in well-established MS
      patients, as well as to obtain a tissue diagnosis of such lesions whenever
      possible in order to determine their precise etiology.

PMID- 9153468
TI  - HHV-8 and AIDS-related CNS lymphoma.
AB  - Human herpesvirus 8 (HHV-8), the Kaposi's sarcoma (KS)-associated herpesvirus, is
      closely related to the transforming Epstein-Barr virus (EBV) and may be detected
      in AIDS-related, EBV-containing, body-cavity-based lymphomas. Accordingly, we
      analyzed 27 EBV-positive, AIDS-related CNS lymphomas for HHV-8 sequences. Only
      one tumor yielded HHV-8 sequences; this tumor arose in a patient with concomitant
      systemic lymphoma and a history of KS. We conclude that HHV-8 is unlikely to have
      a major role in the pathogenesis of AIDS-related, EBV-associated CNS lymphomas.

PMID- 9153469
TI  - Chemotherapy response criteria in malignant glioma.
AB  - No one has ever proven a relationship between the extent of response to
      chemotherapy in malignant glioma and time to progression or survival. We studied
      the predictive value of "imaging response" following two courses of nitrosourea
      based chemotherapy in 136 patients with recurrent astrocytoma/malignant glioma.
      We performed image analysis by blinded side-to-side comparison of sequential
      studies, and categorized response into: partial response (PR) (>50% reduction),
      minor response (MR) (25-50% reduction), stable disease (SD) (<25% change),
      progressive disease (PD) (>25% increase). Patients with PR, MR, and SD did not
      differ with respect to time to progression (TTP) (p > 0.2) or survival (p > 0.2).
      Median TTP was 27 weeks for SD, 43 weeks for MR, and 30 weeks for PR. Patients
      with PD had a significantly reduced survival (p < 0.001). Median survival was 21
      weeks for PD, 53 weeks for SD, 63 weeks for MR, and 48 weeks for PR. The lack of
      relationship between response and TTP may be due to early relapses in patients
      with response, a cytostatic benefit of chemotherapy in some patients who do not
      have an objective response, or a relatively favorable natural history in some
      tumors that do not respond to chemotherapy. Our data do not support the validity
      of current response grading, assessed after two courses of chemotherapy. Further
      research and validation of response criteria is necessary.

PMID- 9153470
TI  - Quantitation of herpes simplex virus type 1 DNA in cells of cerebrospinal fluid
      of patients with herpes simplex virus encephalitis.
AB  - We used a nested polymerase chain reaction assay to quantitate the number of
      viral copies in cells of CSF of eight patients with herpes simplex virus
      encephalitis (HSVE). The viral load was monitored in serial CSF samples during
      the course of disease and correlated to clinical symptoms, radiologic
      manifestations, efficacy of acyclovir treatment, and overall clinical outcome.
      Before treatment, HSV type 1 (HSV-1) copies were detected at a mean value of
      1,786/10(5) (range, 5 to 8,333/10(5) cells; median, 81/10(5) cells). During
      therapy, HSV-1 DNA decreased gradually to a mean value of 6 copies/10(5) cells
      (range, 0 to 33 copies/10(5) cells; median, 0 copies/10(5) cells) within 6 to 21
      days and disappeared or was barely detectable before treatment completion in most
      cases. The HSV-1 burden in the CSF did not clearly correlate with the severity of
      clinical signs or the degree of cranial imaging findings and overall outcome.
      Quantitation of HSV-1 copies allows rapid and reliable monitoring of antiviral
      therapy. The absence of a clear correlation between viral load in the CSF and
      morbidity may suggest a role for indirect mechanisms of brain injury in HSVE.

PMID- 9153471
TI  - Unilateral hyperfusion in brain-perfusion SPECT predicts poor prognosis in acute
      encephalitis.
AB  - We studied 88 patients with acute encephalitis using hexamethylpropyleneamine
      oxime and single photon emission computed tomography (SPECT). All patients had
      been initially treated with intravenous acyclovir. The etiology could be
      disclosed in 37 patients (42%), which included 15 patients with herpes simplex
      encephalitis, 7 with varicella-zoster encephalitis, and 29 with other
      encephalitides (Mycoplasma, adenovirus, influenza, rotavirus, rubella, Epstein
      Barr, arbovirus, syphilis, and tuberculosis). Unilateral hyperperfusion in SPECT
      was an independent predictor of poor prognosis, whereas neither clinical outcome
      variables, such as seizures, state of consciousness, and focal neurologic
      findings, nor CSF or EEG findings were not. Focal unilateral hyperperfusion is an
      indicator of severe inflammation of the brain tissue and predicts a poor outcome
      as assessed in terms of activities of daily living after recovery.

PMID- 9153472
TI  - Epstein-Barr virus encephalomyelitis diagnosed by polymerase chain reaction:
      detection of the genome in the CSF.
AB  - A case of encephalomyelitis with polymerase chain reaction detection of Epstein
      Barr virus (EBV) in the CSF, and concurrent serologic changes consistent with
      acute systemic EBV infection is presented and discussed. We document involvement
      of the brain, spinal cord, and nerve roots, summarize some unusual imaging
      findings, and note the evolution of CSF oligoclonal bands.

PMID- 9153473
TI  - Guamanian neurodegenerative disease: are diabetes mellitus and altered humoral
      immunity clues to pathogenesis?
AB  - On the western Pacific island of Guam, parkinsonism, dementia, and amyotrophic
      lateral sclerosis are highly prevalent but the cause is not known. To assess the
      possibility that the pathologic process extends beyond the nervous system, we
      studied patients with Guamanian neurodegenerative disease (N = 16) and Guamanian
      Chamorro control subjects (N = 16) in the Clinical Research Center of the Mayo
      Clinic, Rochester, MN. The principal abnormalities found in those with
      neurodegenerative disease included diabetes mellitus in 44%, elevated levels of
      serum immunoglobulin A (IgA) in 50%, and elevated IgG in 44%. The mean serum IgM
      level in the patient group was significantly lower than in the control group.
      Diabetes mellitus and elevated IgA and IgG levels were also present in 31% of
      neurologically normal Guamanian subjects. Some of these control subjects,
      however, probably have preclinical neurodegenerative disease, as found in
      previously published postmortem studies. Extensive serologic testing did not
      reveal any consistent profile of autoimmunity. Other blood and urine studies
      failed to identify hematologic, nutritional, renal, hepatic, or metabolic
      abnormalities that distinguished patients. Whether diabetes mellitus or
      abnormalities of immune regulation share common etiopathology with Guamanian
      neurodegenerative disease deserves further study.

PMID- 9153474
TI  - Surface and depth EEG findings in patients with hippocampal atrophy.
AB  - OBJECTIVE: To establish if MRI evidence of hippocampal atrophy (HcA) is an
      independent surrogate of EEG criteria for the diagnosis of medial temporal lobe
      (MTL) epilepsy (MTLE). BACKGROUND: MRI evidence of HcA has been shown to
      correlate with mesial temporal sclerosis (MTS), intracranial evidence of MTL
      seizure onset, and outcome after temporal lobectomy. The reported rate of
      discordance between scalp ictal EEG recordings and MRI evidence of unilateral HcA
      ranges from rare to moderate. We examined the surface and depth ictal EEG
      findings of patients with HcA, as detected by volumetric MRI, to clarify their
      significance in detecting areas of epileptogenicity in this group of patients.
      METHODS: From a group of patients with refractory epilepsy, we identified 119
      patients with HcA (97 with unilateral and 13 with bilateral HcA, 9 with HcA and
      mass lesion). MRI volumetric studies were used to obtain Hc ratios. Absolute
      volumes were used to detect bilateral atrophy. Surface and depth EEG recordings
      were analyzed for localization of ictal abnormalities, and their distribution was
      compared for concordance with the location of HcA. Surgical outcome was reviewed.
      RESULTS: Of the 110 patients with isolated HcA, 63 had surgery; 82% of ictal
      depth EEG onsets were concordant with the atrophic Hc, and 72% ictal surface EEG
      onsets were concordant. Four patients with concordant EEG and HcA failed to
      achieve seizure control with resection of the atrophic Hc. Furthermore, 3
      patients with discordant EEG and HcA had resection of the non-atrophic Hc with
      excellent results. Among the 47 non-operated patients, 54% had discordant or
      unlocalized ictal depth EEG results and 52% had discordant ictal surface EEG.
      Four of the 9 lesional patients with HcA had excellent outcome after lesionectomy
      without hippocampectomy. CONCLUSION: The presence of HcA is not an independent
      predictor of the site of epileptogenesis.

PMID- 9153475
TI  - Epilepsy surgery outcome: comprehensive assessment in children.
AB  - The effect of extratemporal and temporal lobe cortical resection on children with
      intractable epilepsy is not well understood. We evaluated a comprehensive array
      of outcome variables in 33 consecutive children who received epilepsy surgery at
      12 years of age or younger. Twenty-two (67%) children were seizure-free, three
      (9%) had a greater than 90% reduction in seizures, and four had no improvement.
      Antiepileptic drugs (AEDs) were not required in 10 (30%) children and were
      reduced in number in another 10. Six (29%) of 21 tested children had an
      improvement of greater than 10 points in Verbal or Performance IQ after surgery,
      while one (4%) had a decrease greater than 10 points in Verbal IQ. One mild
      hemiparesis and one inferior quadrantanopsia occurred; both were anticipated. We
      used the Child Health Questionnaire (CHQ), a valid and reliable instrument for
      children, to assess health-related quality of life (HRQOL). Six of 12 subscale
      scores of the CHQ were significantly lower in the surgical group compared with
      410 age-matched control subjects. Parents were satisfied with surgical results in
      28 (85%) cases. Pathologic tissue diagnosis and site of resection were not
      associated significantly with any outcome measure. We conclude that surgery
      eliminates seizures and reduces AED requirements in most children with
      intractable epilepsy selected by currently available methods. Further
      investigation is needed to establish the nature and significance of inferior
      scores in the surgical group in the HRQOL domains of physical function, general
      health, and self-esteem.

PMID- 9153476
TI  - Non-epileptic seizures in temporal lobectomy candidates with medically refractory
      seizures.
AB  - Diagnosis of epileptic seizures is often based on temporal lobe epileptiform
      abnormalities appearing on interictal EEG, when reported ictal semiologies are
      consistent with temporal lobe seizures. It is unclear how often such patients
      have non-epileptic seizures. We studied 145 patients who had temporal interictal
      EEG spikes and reported ictal semiology characteristic of temporal lobe seizures,
      with long-term EEG-video-monitoring (LTM) for presurgical evaluation of medically
      refractory seizures. Nonepileptic seizures were unexpectedly recorded in 12 of
      these patients (8%). Outcomes after LTM in patients who had both epileptic
      seizures and nonepileptic seizures demonstrated that the epileptic seizures
      usually were controlled with medications. Our observations support LTM as useful
      in diagnosis of non-epileptic seizures in this group of patients. We suggest that
      ictal recordings always should be performed before epilepsy surgery, in part to
      avoid unintentional surgical treatment of nonepileptic seizures.

PMID- 9153477
TI  - Long-term follow-up after temporal lobe resection for lesions associated with
      chronic seizures.
AB  - A follow-up study was conducted on 60 patients who had standard en bloc anterior
      temporal lobe resection, including mesiotemporal structures, as treatment for
      temporal lobe lesions associated with chronic, medically intractable seizures.
      Lesions were identified as glial tumors, hamartomas, or vascular malformations.
      Long-term outcome was assessed in terms of seizure frequency and certain
      psychosocial sequelae. Seizure onset occurred at an average age of 15 years
      (median = 13.5 years), and patients experienced seizures for an average of 13
      years prior to surgery. The mean time of follow-up was 8.4 years postsurgery
      (median = 6 years). The Kaplan-Meier curve at median follow-up showed a seizure
      free rate of 80%. Late seizure recurrence was documented for three patients; two
      had been seizure-free for 10 years and one for 15 years after surgery, before re
      onset of seizures in the absence of tumor recurrence. A prolonged history of
      seizures prior to surgery was associated with a poorer seizure outcome (p =
      0.06), suggesting that secondary epileptogenesis at sites distant to the lesion
      may develop with years of uncontrolled seizures. There was a low tumor recurrence
      rate of 3.3% (two cases). The psychosocial outcome was generally good, with 67%
      working or engaged in educational studies, and improvement noted in 59% of cases
      for one or more of the psychosocial factors investigated. This study confirms
      that anterior temporal lobe resection for temporal lesions associated with
      chronic seizures is a successful treatment with a high seizure-free rate
      following surgery and good psychosocial outcome.

PMID- 9153478
TI  - Usefulness of polysomnography in epilepsy patients.
AB  - We reviewed the records of 63 adult epilepsy patients who underwent
      polysomnograms in our laboratory since 1985 to determine the indications for
      polysomnography and the results of testing. Reasons for referral included
      excessive daytime sleepiness, suspected obstructive sleep apnea (OSA), and
      characterization of nocturnal spells. The most common polysomnographic diagnosis
      was OSA, although we also found narcolepsy, insufficient sleep syndrome with
      possible idiopathic hypersomnolence, and previously unrecognized nocturnal
      seizures. We treated OSA with continuous positive airway pressure in 28 patients,
      15 of whom were using the device at follow-up appointments. The majority of
      patients treated for OSA or other disorders reported an improvement in sleepiness
      or seizure control. Polysomnography, when indicated, is beneficial in epilepsy
      patients.

PMID- 9153479
TI  - Color vision tests for early detection of antiepileptic drug toxicity.
AB  - A previous suggestion that antiepileptic drugs may induce color vision
      deficiencies prompted us to examine whether color vision deficiencies may occur
      at lower drug serum concentrations than those associated with symptoms of
      neurotoxicity. Eighty patients presenting with epilepsy received monotherapies of
      valproic acid, phenytoin, or carbamazepine; 18 patients did not receive
      antiepileptic drug therapy. Color vision was tested by the Farnsworth-Munsell 100
      hue test, spectral sensitivity, and the newly developed tritan screening plates.
      Patients treated with phenytoin or carbamazepine developed blue-yellow color
      vision deficiencies. In contrast, patients exposed to valproic acid or receiving
      no drug treatment showed normal color vision. There was a significant correlation
      (p < 0.0001) between signs of neurotoxicity induced by phenytoin or carbamazepine
      and blue-yellow color vision deficiencies. In contrast, we found no correlation
      between these signs of neurotoxicity and the drug serum concentrations (p =
      0.0637). Color vision testing in epileptic patients treated with phenytoin or
      carbamazepine appears to be a sensitive method for early detection and monitoring
      of clinical neurotoxicity.

PMID- 9153480
TI  - Depression of motor cortex excitability by low-frequency transcranial magnetic
      stimulation.
AB  - We studied the effects of low-frequency transcranial magnetic stimulation (TMS)
      on motor cortex excitability in humans. TMS at 0.1 Hz for 1 hour did not change
      cortical excitability. Stimulation at 0.9 Hz for 15 minutes (810 pulses), similar
      to the parameters used to induce long-term depression (LTD) in cortical slice
      preparations and in vivo animal studies, led to a mean decrease in motor evoked
      potential (MEP) amplitude of 19.5%. The decrease in cortical excitability lasted
      for at least 15 minutes after the end of the 0.9 Hz stimulation. The mechanism
      underlying this decrease in excitability may be similar to LTD. TMS-induced
      reduction of cortical excitability has potential clinical applications in
      diseases such as epilepsy and myoclonus. Spread of excitation, which may be a
      warning sign for seizures, occurred in one subject and was not accompanied by
      increased MEP amplitude, suggesting that spread of excitation and amplitude
      changes are different phenomena and also indicating the need for adequate
      monitoring even with stimulations at low frequencies.

PMID- 9153481
TI  - Familial schizencephaly associated with EMX2 mutation.
AB  - We describe two brothers aged 8 and 10 affected by severe bilateral
      schizencephaly, carrying an identical point mutation of the homeobox gene EMX2.
      Both children had severe neurologic deficits and mental retardation, although
      they differed in the anatomic extent of the brain malformation and in the
      severity of the clinical picture. The present findings, together with the
      reported cases of schizencephaly associated with EMX2 mutations, support the
      hypothesis that, at least in some cases, schizencephalies are determined by
      deleterious mutations of this homeobox gene. The different morphoclinical
      pictures suggest that, besides the EMX2 mutation, other factors are relevant in
      determining the severity of the brain malformation and clinical picture.

PMID- 9153482
TI  - Functional magnetic resonance imaging and transcranial magnetic stimulation:
      complementary approaches in the evaluation of cortical motor function.
AB  - Functional magnetic resonance imaging (fMRI) and transcranial magnetic
      stimulation (TMS) represent different approaches to mapping the motor cortex.
      fMRI identifies areas of hemodynamic changes during task performance while TMS
      provides electrophysiologic data concerning the localization and density of
      cortical motoneurons. Here we define the spatial correlation between fMRI and TMS
      maps and compared them with direct electrical cortical stimulation (ECS). We
      performed fMRI at 1.5 T on 3 normal subjects and 2 patients with mass lesions
      near the central sulcus using a multislice, asymmetric, spin-echo, echo-planar
      pulse sequence during the performance of a motor task. We also performed focal
      TMS with surface EMG recordings from the muscles primarily involved in the fMRI
      task. We coregistered the stimulation sites in real time with the fMRI maps using
      a frameless stereotactic system. In both patients we also performed ECS of the
      cortex during surgery under local anesthesia. fMRI maps were validated by the
      electrophysiologic data both pre- and intraoperatively. Our results suggest that
      regions of fMRI activation correspond spatially to areas of highest motoneuron
      density as demonstrated by electrophysiologic techniques.

PMID- 9153483
TI  - Object shape processing in the visual system evaluated using functional MRI.
AB  - We used functional MRI (fMRI) to determine the cortical regions activated during
      processing of visual object shape in humans in six men and three women, using a
      paradigm with a baseline condition of simple shape detection and an activated
      condition of object/nonobject shape discrimination. Eight of the nine subjects
      studied showed significant signal changes. Seven of eight showed changes in the
      occipital lobes (five bilateral, two right only, one left only). All eight
      subjects with signal changes exhibited changes in the parietal lobes bilaterally.
      In the occipitotemporal gyri, there were signal changes bilaterally in seven
      subjects and unilaterally, on the right, in one. Activation-related fMRI signal
      increases were also present in the posterior superior and middle temporal gyri in
      seven of the subjects, with four showing bilateral signal changes, two showing
      signal changes on the left only, and one only on the right. The data strongly
      suggest that processing of object shape information in humans activates both the
      ventral and dorsal visual processing pathways ("what" and "where" pathways),
      described previously both in humans and in nonhuman primates.

PMID- 9153484
TI  - Albendazole therapy for neurocysticercosis: a prospective double-blind trial
      comparing 7 versus 14 days of treatment. Cysticercosis Working Group in Peru.
AB  - OBJECTIVE: To compare the effectiveness of two regimens of albendazole therapy
      for neurocysticercosis. DESIGN: Randomized, double-blind clinical trial.
      SETTINGS: Patients admitted to neurologic wards in Lima, Peru. PATIENTS: Adult
      patients with active neurocysticercosis demonstrated by CT and Western blot
      (immunoblot). INTERVENTION: One week (n = 25) versus 2 weeks (n = 25) of
      albendazole therapy. MEASUREMENTS: Decrease in the number of cysts on CT.
      RESULTS: Effectiveness of albendazole was 78%, with no difference between the
      groups when compared 3 months after therapy. Complete cure was obtained in only
      38% of patients. Patients with more than 20 cysts had poorer responses to
      therapy. The clinical course and EEG evolution improved in most patients. Side
      effects were present in 38% of patients, mainly mild, transient gastrointestinal
      symptoms. Therapy was also associated with exacerbation of neurologic symptoms.
      Two patients died in the first year after therapy, both because of aggregated
      infections of ventricle-peritoneal shunts. One-year follow-up CT showed lesions
      in three of 10 patients presumed to be cured 3 months after therapy. CONCLUSIONS:
      Extension of albendazole therapy for more than 7 days adds no benefits for the
      patients.

PMID- 9153486
TI  - Temporal lobe arachnoid cyst-attention deficit disorder syndrome: role of the
      electroencephalogram in diagnosis.
AB  - I report three childhood cases of temporal lobe arachnoid cyst in association
      with attention deficit hyperactivity disorder (ADHD). The cysts were identical in
      location, situated in the left middle cranial fossa, and involved the medial
      aspect of the temporal lobe. The diagnosis by MRI was determined following EEGs
      obtained because of headaches, episodes suggestive of partial seizures or
      tremors, and abnormal neurologic signs. The etiology of the cysts appeared to be
      developmental and not related to trauma or hemorrhage. EEGs showed focal
      epileptiform or slow wave abnormalities involving the left temporal region and
      correlating with the location of the structural temporal fossa lesions. Surgery
      was not advised, and headaches resolved after dietary modification or when
      methylphenidate medication for ADHD was discontinued. The relation of the
      arachnoid cyst to the headaches is not definitely determined, but a causal
      association with the ADHD is considered plausible because of coincidental
      learning and language disabilities that might be explained by temporal lobe and
      sylvian region pathology. This appears to be the first report of the association
      of ADHD and temporal fossa arachnoid cyst in children. The EEG is a valuable
      diagnostic test in patients with ADHD complicated by headaches, seizures, or
      focal neurologic signs. Future cases of arachnoid cyst involving the temporal
      lobe and diagnosed because of headache or seizures should be investigated
      psychologically for associated attention deficits and learning disabilities.

PMID- 9153485
TI  - Schizencephaly: correlations of clinical and radiologic features.
AB  - Schizencephaly is an uncommon congenital disorder of cerebral cortical
      development. Although a well-recognized cause of seizures and developmental
      deficits in children, previous reports describe the range of neurodevelopmental
      outcome in only 47 patients. We report the clinical and cranial imaging features
      of 47 children with unilateral open-lip (17), unilateral closed-lip (12),
      bilateral open-lip (12), and bilateral closed-lip (6) schizencephaly, as defined
      radiologically. The schizencephalic cleft occurred more often in the anterior
      than in the posterior neocortex. Children with closed-lip schizencephaly
      presented with hemiparesis or motor delay whereas patients with open-lip
      schizencephaly presented with hydrocephalus or seizures. Forty-three patients
      (91%) had associated cerebral developmental anomalies, most commonly absence of
      the septum pellucidum (45%) and focal cortical dysplasia (40%). There was a
      history of seizures in 57% of cases, a third of which were classified as
      difficult to control. Neurodevelopmental outcome was generally poor, with 51% of
      patients (24/47) having severe deficits, 32% of patients (15/47) having moderate
      impairment, and 17% of patients (8/47) having mild or no problems. Patients with
      closed-lip schizencephaly were more likely to have a mild to moderate outcome
      than those with open-lip type (78% versus 31%; p < 0.05). Children with
      unilateral schizencephaly had a mild or moderate outcome more frequently than
      those with bilateral lesions (62% versus 28%; p < 0.05). Children who had
      involvement of a single lobe accounted for 88% of those with mild outcomes and
      53% of those with moderate outcomes. Unilateral closed-lip schizencephaly was
      associated with the best neurodevelopmental outcome; in contrast, 11 of 12
      children with bilateral open-lip clefts had severe disabilities. Language
      development was significantly more likely to be normal in those children with
      unilateral schizencephaly than in those with bilateral clefts (48% versus 6%; p <
      0.002). Thus, the presentation and outcome of children with schizencephaly are
      quite variable but are related to the extent of cortex involved in the
      schizencephalic defect.

PMID- 9153488
TI  - Cramps and minimal EMG abnormalities as preclinical manifestations of spinal
      muscular atrophy patients with homozygous deletions of the SMN gene.
AB  - The characterization of deletions in the SMN gene provides a helpful tool to
      confirm the diagnosis of spinal muscular atrophy (SMA). However, there may be
      homozygous deletions of the SMN gene in some unaffected siblings of SMA type II
      and III patients. We present two SMA families with affected siblings
      demonstrating a homozygous deletion of the SMN gene with extremely different
      phenotypes. We propose a preclinical category of an SMA patient with homozygous
      deletion of the SMN gene: those with minimal expression of the disease including
      cramps and EMG abnormalities that may develop the complete SMA phenotype in the
      future.

PMID- 9153487
TI  - Muscle fiber atrophy in leg muscles after botulinum toxin type A treatment of
      cervical dystonia.
AB  - Previous electrophysiologic studies on the effects of local injections of
      botulinum toxin type A (BTX-A) have indicated impaired neuromuscular transmission
      in distant muscles. To further study possible distant effects of repeated BTX-A
      injections, we obtained percutaneous muscle biopsies of the vastus lateralis
      muscle from 11 patients with cervical dystonia. We examined the biopsies with
      histopathology and morphometry, and compared them with age-matched healthy
      controls. There was an increased frequency of angular atrophic type IIB fibers in
      the patient group, and the mean size of IIB fibers was significantly smaller (p <
      0.05). In addition, there was a negative correlation between accumulated dose of
      botulinum toxin and relative size of type IIA fibers (p < 0.05). We postulate
      that the observed atrophy is due to distant effects of botulinum toxin causing
      progressive denervation-like changes in non-treated muscle. This observation
      calls for further, prospective studies of the long-term effects of the treatment.

PMID- 9153489
TI  - Interferon beta results in immediate reduction of contrast-enhanced MRI lesions
      in multiple sclerosis patients followed by weekly MRI.
AB  - Interferon beta-1a and -1b reduce the frequency and severity of clinical
      exacerbations, and reduce both T2-weighted and contrast-enhanced MRI activity in
      patients with multiple sclerosis (MS). Several recent reports suggest that at the
      initiation of treatment there may be transient worsening of symptoms associated
      with the induction of interferon gamma-secreting cells. We studied eight MS
      patients with weekly brain MRI's after starting interferon beta treatment, and
      found immediate reduction in the number of contrast-enhancing lesions. Several
      patients did experience recurrence of previous symptoms without concomitant
      opening of the blood brain barrier on contrast-enhanced MRI. These data suggest
      that the symptoms described after the initiation of interferon beta are not
      associated with new disease activity, but rather may be related to preexisting
      lesions. This has implications for both understanding the immunopathogenesis of
      the disease and for its treatment.

PMID- 9153490
TI  - Traumatic brainstem deafness with normal brainstem auditory evoked potentials.
AB  - A 48-year-old woman became totally deaf after a head injury. Magnetic resonance
      imaging showed bilateral contusions around the inferior colliculi and the
      brainstem auditory evoked potentials (BAEP) failed to show any abnormality. This
      case demonstrates that small, symmetrical, bilateral lesions around the inferior
      colliculi may cause deafness and may still be associated with a normal BAEP.

PMID- 9153491
TI  - Creutzfeldt-Jakob disease after extracranial dura mater embolization for a
      nasopharyngeal angiofibroma.
AB  - We report a 25-year-old man with Creutzfeldt-Jakob disease (CJD) who had received
      dura mater embolization in the external carotid artery for a nasopharyngeal
      angiofibroma 90 months earlier. The patient was heterozygotous (Met/Val) at codon
      129. This case suggests that dura mater embolization can be responsible for the
      CJD.

PMID- 9153492
TI  - A case of spinal cord decompression sickness presenting as partial Brown-Sequard
      syndrome.
AB  - Type II decompression sickness (DCS) usually manifests as myelopathy; however,
      there are no reports of Brown-Sequard syndrome in association with diving
      accidents. We report a 35-year-old man who developed type II DCS presenting as
      partial Brown-Sequard syndrome. MRI of the thoracic spine revealed two punctate
      foci of increased signal intensity in the right T6 spinal cord.

PMID- 9153493
TI  - MR imaging of progressive downward herniation of the diencephalon.
AB  - Some clinicians have challenged the clinicopathologic correlation in patients
      with brain herniation from acute mass lesions. Earlier studies have questioned
      the significance of downward displacement of the brainstem in supratentorial
      herniation. Using recent generation MRI, we studied a patient with an acute
      hemorrhagic infarction. MRI demonstrated significant compression of the
      diencephalon with downward displacement of the midbrain and hyperintensity on T2
      weighted sequences in the lateral mesencephalon during progression from early
      diencephalic stage to midbrain upper pons stage of herniation. This is the first
      intra vitam documentation of diencephalic herniation by MR imaging and confirms
      rostrocaudal deterioration usually found at autopsy.

PMID- 9153494
TI  - Meningiomas: the decision not to operate.
AB  - In a consecutive series of 100 patients diagnosed with meningiomas, we advised 12
      patients not to have surgery, and followed them from 3.3 to 12.8 years (mean, 8.8
      years). The two determinants of this decision were either absence of related
      neurologic symptoms or signs and concern about high operative risk of neurologic
      impairment. Serial imaging studies showed meningioma growth in only one of the 12
      unoperated patients and only one had convincing progression of neurologic
      impairment.

PMID- 9153495
TI  - Interictal cortical excitability to magnetic stimulation in familial hemiplegic
      migraine.
AB  - We studied interictal cortical excitability with magnetic stimulation in
      controls, in patients with migraine with aura, and in patients with familial
      hemiplegic migraine (FHM), in which ictal hemiparesis occurs. Amplitudes (p <
      0.05) and amplitude ratios (p < 0.01) revealed heightened excitability in
      migraine with aura when compared to controls. In patients with FHM, mean
      thresholds were higher (p < 0.001) and conduction times longer (p < 0.01) than in
      controls. In FHM, amplitudes were lower on the ictally paretic side of the body
      than on the other (p < 0.05). Patients with FHM may have increased interictal
      cortical excitability, complicated by decreased excitability of the affected
      side.

PMID- 9153496
TI  - Electrocerebral inactivity associated with obstructive sleep apnea.
AB  - We report a child who demonstrates near electrocerebral silence secondary to
      obstructive apnea during polysomnography. The mechanism of this suppression of
      cortical activity appears to be related to hypoxemia in the absence of a
      malignant arrhythmia.

PMID- 9153497
TI  - Gabapentin for idiopathic trigeminal neuralgia: report of two cases.

PMID- 9153498
TI  - Incontinence during treatment with gabapentin.

PMID- 9153499
TI  - Efficacy of pyridoxal phosphate in treating an adult with intractable status
      epilepticus.

PMID- 9153500
TI  - Human T-lymphotropic virus type I-associated myelopathy/tropical spastic
      paraparesis and systemic lupus erythematosus.

PMID- 9153501
TI  - Creutzfeldt-Jakob disease after an embolization of intercostal arteries with
      cadaveric dura mater suggesting a systemic transmission of the prion agent.

PMID- 9153502
TI  - Migraine and increased migraine.

PMID- 9153503
TI  - Retrospinal tract.

PMID- 9153504
TI  - Steroid therapy in AD.

PMID- 9153506
TI  - Spinal cord watershed.

PMID- 9153507
TI  - Hypothyroid dementia.

PMID- 9153508
TI  - Spontaneous dissections.

PMID- 9153509
TI  - Predictors in stroke outcome.

PMID- 9153510
TI  - Predictors in stroke outcome.

PMID- 9153511
TI  - Root enhancement in GBS.

PMID- 9153512
TI  - Serum prolactate in syncope.

PMID- 9153513
TI  - Spinal cord infarction.

PMID- 9153514
TI  - Alcohol withdrawal and Tourette's syndrome.

PMID- 9153515
TI  - Diffusion-weighted MRI: an ECG for "brain attack"?

PMID- 9153516
TI  - Diffusion-weighted MRI for diagnosis and treatment of ischemic stroke.

PMID- 9153517
TI  - The quest for unbiased research: randomized clinical trials and the CONSORT
      reporting guidelines.

PMID- 9153518
TI  - Clinical utility of diffusion-weighted magnetic resonance imaging in the
      assessment of ischemic stroke.
AB  - Diffusion-weighted imaging (DWI) detects small changes in water diffusion that
      occur in ischemic brain. This study evaluated the clinical usefulness of a phase
      navigated spin-echo DWI sequence compared with T2-weighted magnetic resonance
      imaging (T2W MRI) in patients with cerebral ischemia and assessed apparent
      diffusion coefficient (ADC) and T2-weighted imaging (T2WI) changes over time. ADC
      values and T2 ratios of image intensity were measured from the region of ischemia
      and from the corresponding contralateral brain region. The clinical histories of
      patients with DWI scans obtained over the course of 1 year were reviewed to
      ascertain whether DWI aided in clinical diagnosis or management. Of 103 scans
      obtained a mean of 10.4 days after symptom onset, DWI detected six lesions not
      seen on T2WI and discriminated two new infarcts from old lesions. DWI was most
      useful within 48 hours of the ictus. The evolution of ADC values and T2 ratios
      was evaluated in 26 cases with known symptom onset times. ADC values were low at
      less than 1 week after stroke onset and became elevated at chronic time points.
      T2 ratios were near normal acutely, increasing thereafter. DWI was superior to
      T2W MRI in detecting acute stroke, whereas both techniques assisted in
      determining lesion age.

PMID- 9153519
TI  - Enlargement of human cerebral ischemic lesion volumes measured by diffusion
      weighted magnetic resonance imaging.
AB  - We aimed to determine the frequency and time course of the enlargement of
      ischemic cerebral lesions following human stroke and to study the effect of the
      state of perfusion on lesion enlargement. Acute lesion volumes were measured on
      diffusion-weighted magnetic resonance images and compared with lesion volumes
      measured on T2-weighted images at 7 days or later. Forty-four measurements were
      performed between 2 and 53 hours after stroke onset in 28 patients. Thirteen
      patients also had magnetic resonance perfusion imaging performed. In 12 (43%) of
      28 patients the initial lesion volume increased by 20% or more. The number of
      studies showing enlargement of the ischemic lesion volume ranged from 12 (43%) of
      28 at or after 2 hours to 10 (38%) of 26 at or after 6 hours, 5 (33%) of 15 at or
      after 24 hours, and 2 (33%) of 6 at or after 48 hours. In 7 of the 10 patients in
      whom the hypoperfusion volume acutely exceeded the volume of the abnormality on
      diffusion-weighted images, lesion volume increased by 20% or more. This study
      provided evidence that substantial enlargement of human cerebral ischemic lesion
      volumes can occur beyond the first 6, 12, or 24 hours after onset. A mismatch
      acutely between the region of hypoperfusion (larger) and the region of diffusion
      abnormality (smaller) may be predictive of ischemic lesion enlargement.

PMID- 9153520
TI  - Brain impairment in well-nourished chronic alcoholics is related to ethanol
      intake.
AB  - To determine the influence of chronic ethanol intake on the central nervous
      system, we studied 40 asymptomatic, well-nourished, chronic alcoholics (mean age,
      42.6 +/- 9.1 years) and 20 age-, sex-, and education-matched control subjects.
      Studies included neuropsychological testing, visual and short-latency auditory
      evoked potentials, and morphometric analysis of computed tomography scans. The
      mean daily ethanol consumption of the alcoholics was 204 gm over an average of
      26.4 years. Compared to control subjects, chronic alcoholics exhibited a
      significant prolongation of the P100 latency of visual evoked potentials, and a
      prolongation and reduction in the amplitude of the latency of the V wave of short
      latency auditory evoked potentials. These abnormalities were related to the
      lifetime dose of ethanol consumed. Brain morphometric analysis showed that
      alcoholics had a significantly greater degree of brain shrinkage with age,
      compared to control subjects. The cortical atrophy index correlated significantly
      with the lifetime ethanol consumption. Neuropsychological testing in alcoholics
      compared to controls revealed a significant impairment of frontal skills that was
      related to age, degree of scholarship, and the presence of frontal atrophy. In
      conclusion, well-nourished chronic alcoholics exhibited significant brain
      impairment, as demonstrated by neuropsychological testing, evoked potentials, and
      brain morphometric analysis, which was correlated with the lifetime dose of
      ethanol consumed.

PMID- 9153521
TI  - Regional and cellular expression of the dentatorubral-pallidoluysian atrophy gene
      in brains of normal and affected individuals.
AB  - Dentatorubral-pallidoluysian atrophy is an autosomal dominant neurodegenerative
      disorder characterized by dementia and spinocerebellar degeneration. Recently,
      part of the gene responsible for this disorder was cloned containing a CAG
      repeat, and predominant neuronal expression of the gene was proved only through
      Northern blot analysis in rats. In this study, we investigated the regional and
      cellular expression of the dentatorubral-pallidoluysian atrophy gene in the
      central nervous system of normal and affected humans, as well as in rat brains.
      In normal control human subjects, the gene messenger RNA was present in all brain
      regions examined, with the highest levels seen in the cerebellum, hippocampus,
      substantia nigra, and pontine nuclei. Its expression in the striatum, globus
      pallidus, and cerebral cortex was intermediate. The gene was expressed
      predominantly in neurons; a low but significant level of expression was also seen
      in glial cells. Neurons susceptible to degeneration in dentatorubral
      pallidoluysian atrophy did not selectively express high or low levels of its gene
      messenger RNA. In brains affected by the disorder, the distribution and levels of
      gene messenger RNA were comparable to those of the normal controls in all the
      areas. In the rat brains, gene messenger RNA expression was very similar to that
      in human brain. It was also expressed predominantly in neurons, while low-level
      expression was observed in glial cells. It is apparent from these results that
      the presence of expanded trinucleotide repeats in dentatorubral-pallidoluysian
      atrophy does not result in the absence of its gene messenger RNA expression or in
      altered patterns or levels of expression.

PMID- 9153522
TI  - Atrophy of the corpus callosum, cognitive impairment, and cortical hypometabolism
      in progressive supranuclear palsy.
AB  - Recent studies disclosed neurofibrillary degeneration in layer 3 of the
      association cortex in patients with progressive supranuclear palsy. This lesion
      may be associated with corpus callosum atrophy and may impair the function of
      cortical regions indispensable for complex cognitive activity. To investigate
      whether corpus callosum atrophy is associated with cognitive impairment and
      cerebral cortical hypometabolism, we studied 10 patients with progressive
      supranuclear palsy using magnetic resonance imaging and positron emission
      tomography with fluorodeoxyglucose as a tracer. Compared with 23 age-matched
      control subjects, the patients had significantly decreased callosal area-skull
      area ratios, with anterior predominance of the degree of atrophy. The corpus
      callosum atrophy was accompanied by a decreased mean cortical glucose metabolic
      rate, predominantly in the frontal region of the cortex, and poor performance on
      the picture arrangement subtest of the Wechsler Adult Intelligence Scale and the
      verbal fluency task. We conclude that corpus callosum atrophy with anterior
      predominance is present in progressive supranuclear palsy, and that this atrophy
      is associated with cognitive impairment and cerebral cortical hypometabolism,
      especially in the frontal cortical region. Corpus callosum atrophy may reflect
      the pathological changes in the cerebral cortex, accentuated in the frontal
      region, that contribute to the development of frontal lobe dysfunction in this
      disease.

PMID- 9153523
TI  - The absence of an apolipoprotein epsilon4 allele is associated with a more
      aggressive form of Alzheimer's disease.
AB  - We investigated the relationship between APOE genotype and rate of disease
      progression and survival in 99 patients with probable Alzheimer's disease (AD)
      who were followed biannually for up to 6 years. Patients were stratified into two
      groups, those with and without at least one APOE epsilon4 allele. The rate of
      decline in modified Mini-Mental State Examination scores was slower, the presence
      of extrapyramidal signs was decreased, and the development of myoclonus occurred
      later among patients with APOE epsilon4 alleles compared with patients with other
      genotypes. Compared with patients without an APOE epsilon4 allele, the risk of
      mortality was also decreased in patients with at least one epsilon4 allele (RR =
      0.38; CI = 0.17-0.84, p < 0.02). Because the decline in mental ability as well as
      the development of myoclonus and extrapyramidal signs are consistent
      manifestations of disease progression, our results imply that APOE epsilon4 is
      associated with a less aggressive form of AD.

PMID- 9153524
TI  - Cortical reorganization in patients with facial palsy.
AB  - Possible changes in the organization of the cortex in patients with facial palsy,
      serving as a model of peripheral motor deefferentation, were investigated by
      using transcranial magnetic stimulation (TMS) and positron emission tomography
      (PET). With TMS, the size of the area producing muscle-evoked potentials (MEPs)
      of the abductor pollicis brevis muscle, the sum of MEP amplitudes within this
      area, and the volume over the mapping area were compared between both hemispheres
      in 8 patients. With PET, increases in regional cerebral blood flow, measured with
      the standard H2(15)O2 bolus injection technique, were compared between 6 patients
      and 6 healthy volunteers during sequential finger opposition. Patients moved the
      hand ipsilateral to the facial palsy, the control subjects the right hand. Of 9
      patients in total, 5 participated in both experiments. With both methods, an
      enlargement of the hand field contralateral to the facial palsy was found,
      extending in a lateral direction, into the site of the presumed face area. The
      PET data showed that the enlargement of the hand field in the somatosensory
      cortex (SMC) is part of a widespread cortical reorganization, including the
      ipsilateral SMC and bilateral secondary motor and sensory areas. We report for
      the first time, using two different noninvasive methods, that peripheral, mere
      motor deefferentation is a sufficient stimulus for reorganizational changes in
      the healthy adult human cortex.

PMID- 9153525
TI  - Juvenile-onset spinal muscular atrophy caused by compound heterozygosity for
      mutations in the HEXA gene.
AB  - Progressive proximal muscle weakness is present both in spinal muscular atrophy
      (SMA) type III (Kugelberg-Welander disease) and in GM2 gangliosidosis, diseases
      that segregate in an autosomal recessive fashion. The SMN gene for SMA and the
      HEXA gene for GM2 gangliosidosis were investigated in a woman with progressive
      proximal muscle weakness, long believed to be SMA type III (Kugelberg-Welander
      type). She and her family underwent biochemical studies for GM2 gangliosidosis.
      Analysis of SMN excluded SMA. Biochemical studies on GM2 gangliosidosis showed
      deficiency in hexosaminidase A activity and increased GM2 ganglioside
      accumulation in the patient's fibroblasts. The HEXA gene was first analyzed for
      the Gly269-->Ser mutation characteristic for adult GM2 gangliosidosis. Since the
      patient was carrying the adult mutation heterozygously, all 14 exons and adjacent
      intron sequences were analyzed. A novel mutation in exon 1 resulting in an A-to-T
      change in the initiation codon (ATG to TTG) was identified. The adult patient is
      a compound heterozygote, with each allele containing a different mutation.
      Although mRNA was transcribed from the novel mutant allele, expression
      experiments showed no enzyme activity, suggesting that neither the TTG nor an
      alternative codon serve as an initiation codon in the HEXA gene.

PMID- 9153526
TI  - Cerebral generators involved in the pathogenesis of the restless legs syndrome.
AB  - The pathophysiology of periodic limb movements and sensory leg discomfort in the
      restless legs syndrome is unknown. With high-resolution functional magnetic
      resonance imaging, we localized for the first time cerebral generators associated
      with sensory leg discomfort and periodic limb movements in 19 patients with
      restless legs syndrome. During sensory leg discomfort there was mainly bilateral
      activation of the cerebellum and contralateral activation of the thalamus. During
      the combined periodic limb movement and sensory leg discomfort conditions,
      patients also showed activity in the cerebellum and thalamus. In contrast to the
      sensory leg discomfort condition alone, the combined condition was associated
      with additional activation in the red nuclei and brainstem close to the reticular
      formation. Voluntary imitation of periodic limb movements by patients and control
      subjects was not associated with brainstem activity, but with additional
      activation in the globus pallidus and motor cortex. These findings indicate that
      cerebellar and thalamic activation may occur because of sensory leg discomfort
      and that the red nucleus and brainstem are involved in the generation of periodic
      limb movements in patients with restless legs syndrome.

PMID- 9153527
TI  - Oxidative damage and metabolic dysfunction in Huntington's disease: selective
      vulnerability of the basal ganglia.
AB  - The etiology of the selective neuronal death that occurs in Huntington's disease
      (HD) is unknown. Several lines of evidence implicate the involvement of energetic
      defects and oxidative damage in the disease process, including a recent study
      that demonstrated an interaction between huntingtin protein and the glycolytic
      enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Using spectrophotometric
      assays in postmortem brain tissue, we found evidence of impaired oxidative
      phosphorylation enzyme activities restricted to the basal ganglia in HD brain,
      while enzyme activities were unaltered in three regions relatively spared by HD
      pathology (frontal cortex, parietal cortex, and cerebellum). Citrate synthase
      corrected complex II-III activity was markedly reduced in both HD caudate (-29%)
      and putamen (-67%), and complex IV activity was reduced in HD putamen (-62%).
      Complex I and GAPDH activities were unaltered in all regions examined. We also
      measured levels of the oxidative damage product 8-hydroxydeoxyguanosine (OH8dG)
      in nuclear DNA, and superoxide dismutase (SOD) activity. OH8dG levels were
      significantly increased in HD caudate. Cytosolic SOD activity was slightly
      reduced in HD parietal cortex and cerebellum, whereas particulate SOD activity
      was unaltered in these regions. These results further support a role for
      metabolic dysfunction and oxidative damage in the pathogenesis of HD.

PMID- 9153528
TI  - Leukodystrophy in patients with ovarian dysgenesis.
AB  - We describe clinical, biochemical, pathological, and spectroscopic findings in 4
      women, aged 15 to 29 years, from three unrelated families who had a unique
      combination of a central nervous system white matter disease and primary ovarian
      failure. All had normal initial development but 3 had borderline low IQ and
      academic difficulties in primary school. Puberty did not develop in 2 patients
      and was arrested in a third patient. The fourth patient had premature ovarian
      failure at the age of 13 years. Head magnetic resonance imaging showed diffuse
      white matter disease, with frontal cortical atrophy in the most clinically
      advanced patient. All patients had normal karyotype and normal findings on
      extensive evaluations for known leukodystrophies, for other metabolic diseases,
      and for causes of ovarian failure. Proton magnetic resonance spectroscopic
      imaging showed reduction of choline-containing compounds in the affected white
      matter in all patients and reduction of N-acetylaspartate in the unaffected
      frontal white matter of 2 patients. All patients had evidence of primary gonadal
      insufficiency with a normal hypothalamic-hypophyseal axis. Pathological analysis
      showed streak ovaries in 1 patient and signs of hypomyelination, and gliosis on
      brain biopsy in another patient. In conclusion, we present a novel group of
      patients who have in common leukodystrophy, primary ovarian dysfunction, and
      magnetic resonance spectroscopic abnormalities.

PMID- 9153529
TI  - Periventricular nodular heterotopia and intractable temporal lobe epilepsy: poor
      outcome after temporal lobe resection.
AB  - We describe 5 women and 5 men with periventricular nodular heterotopia and
      electroclinical features suggestive of temporal lobe epilepsy, who were
      surgically treated for control of medically refractory seizures. Magnetic
      resonance imaging revealed bilateral periventricular nodular heterotopia in 7 of
      the 10 patients. Because of the lack of clear localization, 6 patients were
      studied with intracranial depth electrode recordings. Seizures were of
      hippocampal onset (3 patients), regional temporal lobe onset (2 patients), or
      occipital-temporal onset (1 patient). Anterior temporal lobectomy was performed
      in 6 patients; selective amygdalohippocampectomy, in 1; and anterior temporal
      lobectomy plus resection of the heterotopic tissue, in 3. None of the 9 patients
      followed for more than 12 months postoperatively were seizure free. Two patients
      were initially seizure free for approximately 18 months, but then seizures
      recurred. One patient had a major reduction in seizure frequency at a 39-month
      follow-up after most of the unilateral heterotopic tissue was included in the
      temporal resection. Temporal resection did not lead to a long-term favorable
      outcome in this group of patients with periventricular nodular heterotopia and
      epileptogenic discharges involving the temporal lobe. This suggests a more
      widespread disorder with epileptogenic activity possibly originating in or near
      the heterotopic tissue. The clinical and electrographic features of
      periventricular nodular heterotopia pointing to temporal lobe origin are
      misleading and temporal resection does not result in long-term cessation of
      seizures.

PMID- 9153530
TI  - Increases in soluble VCAM-1 correlate with a decrease in MRI lesions in multiple
      sclerosis treated with interferon beta-1b.
AB  - Interferon beta-1b reduces clinical exacerbations and disease activity in
      multiple sclerosis as shown by magnetic resonance imaging, but the mechanism of
      action is unknown. We investigated the correlation between the levels of soluble
      adhesion molecules and a reduction in contrast-enhancing lesions on gadopentetate
      dimeglumine magnetic resonance images after treatment with interferon beta-1b. We
      determined levels of soluble vascular cell adhesion molecule-1, intercellular
      adhesion molecule-1, E-selectin, L-selectin, and tumor necrosis factor receptor
      (60 kd) in monthly serum samples from patients with definite multiple sclerosis
      before and during treatment with interferon beta-1b. The level of soluble
      adhesion molecules was correlated with the number of newly enhancing lesions on
      monthly contrast-enhanced images. Levels of soluble vascular cell adhesion
      molecule during treatment were significantly increased compared to control or
      pretreatment values. The median levels (ng/ml) of this adhesion molecule were
      580.3 (range; 373.0-640.7) for the healthy subjects, and 551.4 (489.7-875.5) for
      patients prior to treatment and 847.9 (591.5-1,232.9) during treatment. Levels of
      the other soluble adhesion molecules and soluble tumor necrosis factor receptor
      were not significantly changed during treatment. The increase in soluble vascular
      cell adhesion molecule correlated with a decrease in the number of contrast
      enhancing lesions on magnetic resonance images. These data suggest a novel
      mechanism of action for interferon beta-1b by direct interference with the
      adhesion cascade, which may prevent activated T cells from trafficking into the
      central nervous system.

PMID- 9153531
TI  - Phenotypic variability in Friedreich ataxia: role of the associated GAA triplet
      repeat expansion.
AB  - We studied genotype-phenotype correlations in a group of 100 patients with
      typical Friedreich ataxia (FRDA), and in three groups of patients with atypical
      clinical presentations, including 44 Acadian FRDA, 8 late-onset FRDA (LOFA), and
      6 FRDA with retained reflexes (FARR). All patients, except 3 with typical FRDA,
      carried two copies of the FRDA-associated GAA triplet repeat expansion. Overall,
      the phenotypic spectrum of FRDA appeared to be wider than defined by the
      currently used diagnostic criteria. Our study indicated the existence of several
      sources of variability in FRDA. Patients with larger GAA expansions tended to
      have earlier onset and were more likely to show additional manifestations of the
      disease. Mitotic instability of the expanded GAA repeats may partially account
      for the limited degree of correlation between expansion sizes as determined in
      lymphocytes and clinical parameters. Some clinical variants associated with
      specific FRDA haplotypes, such as Acadian FRDA and FARR, turned out to be
      unrelated to expansion sizes. No polymorphism in the frataxin coding sequence
      could be associated with these clinical variants.

PMID- 9153532
TI  - Endoglin gene polymorphism as a risk factor for sporadic intracerebral
      hemorrhage.
AB  - Intracerebral hemorrhage (ICH) is a common and serious type of stroke. Recent
      studies have shown that inherited factors that affect the development of the
      vessel wall can increase the risk of ICH. We studied endoglin as a candidate gene
      in patients with sporadic ICH, since mutations in this gene can cause
      telangiectasia formation. One hundred three patients with sporadic ICH and 202
      controls were studied. The polymerase chain reaction and single-strand
      conformational polymorphism analysis were used to screen for mutations in exon 7
      of the endoglin gene. No coding mutations in exon 7 were identified in the ICH
      patients or controls. A 6-base intronic insertion was found 26 bases beyond the
      3' end of exon 7. The homozygous form of the insertion was present in 9 of 103
      (8.7%) ICH patients compared with 4 of 202 (2.0%) controls, p = 0.012 (odds ratio
      4.8 [95% confidence interval, 1.28, 21.60]). Analysis of the endoglin transcript
      around the insertion did not reveal any changes in the RNA sequence. There were
      no obvious clinical features that distinguished the ICH patients with the
      homozygous insertion from the other patients. The pathophysiologic mechanism
      underlying this association remains to be determined.

PMID- 9153533
TI  - Allelic heterogeneity of Mediterranean myoclonus and the cystatin B gene.
AB  - Mediterranean myoclonus is a progressive myoclonus epilepsy with autosomal
      recessive inheritance. Another form has been described in Finland, the so-called
      Baltic myoclonus. Mediterranean myoclonus and Baltic myoclonus are also known as
      Unverricht-Lundborg disease. Linkage analyses have shown that the genes for both
      these forms of myoclonus are closely linked to 21q22.3 DNA markers, suggesting
      that they are caused by mutations at the same locus (EPM1). Recently, two
      heterozygous mutations were found in the cystatin B gene in patients with
      Unverricht-Lundborg disease. We report recombinational and linkage disequilibrium
      mapping of EPM1, and cystatin B gene sequencing, in 14 consanguineous pedigrees
      with Mediterranean myoclonus. Linkage to 21q22.3 DNA markers was observed in all
      these families. Haplotype analysis suggests that a common mutation segregates
      within these pedigrees, and that this mutation is different from the common one
      responsible for the Finnish form of Unverricht-Lundborg disease. No mutation was
      found in the exons or splice junctions of the cystatin B gene in the 14
      pedigrees.

PMID- 9153534
TI  - CAG repeat number governs the development rate of pathology in Huntington's
      disease.
AB  - We compared the number of CAG repeats, the age at death, and the severity of
      neuropathology in 89 Huntington's disease brains. We found a linear correlation
      between the CAG repeat number and the quotient of the degree of atrophy in the
      striatum (the brain region most severely affected in Huntington's disease)
      divided by age at death, with an intercept at 35.5 repeats. The largest CAG
      repeat length, therefore, at which no pathology is expected to develop is 35.5.
      These results imply that striatal damage in Huntington's disease is almost
      entirely a linear function of the length of the polyglutamine stretch beyond 35.5
      glutamines multiplied by the age of the patient. Thus, it is predicted that the
      pathological process develops linearly from birth. Analysis of other measures of
      striatal function could test this hypothesis and might determine when treatment
      for CAG repeat diseases should start.

PMID- 9153535
TI  - A subset of senile dementia with high incidence of the apolipoprotein E epsilon2
      allele.
AB  - There is a subset of very elderly patients with senile dementia in whom abundant
      neurofibrillary tangles are present, mainly in the hippocampal region, without a
      significant number of senile plaques. In a retrospective neuropathological
      examination of 239 dementia patients, 14 were found to have this type of senile
      dementia. The apolipoprotein E epsilon2, epsilon3, and epsilon4 allele
      frequencies in this patient group were 0.39, 0.50, and 0.11, respectively. Such a
      high frequency of the epsilon2 allele suggests that this type of dementia is
      distinct from Alzheimer's disease not only from a neuropathological but also from
      a genetic viewpoint.

PMID- 9153536
TI  - Dutch hereditary cerebral amyloid angiopathy: structural lesions and
      apolipoprotein E genotype.
AB  - Hereditary cerebral hemorrhage with amyloidosis-Dutch type is caused by a
      mutation at codon 693 of the beta amyloid precursor protein gene. The disease is
      clinically characterized by strokes and dementia. In addition to cerebral
      plaques, cerebral amyloid angiopathy is the pathological hallmark. We
      investigated the correlation between radiological (white matter hyperintensities
      and focal lesions on magnetic resonance images) and pathological lesions
      (cerebrovascular amyloid angiopathy and plaques) and the apolipoprotein E
      genotype in patients with the disease. Twenty-five patients were studied using
      magnetic resonance imaging, and brain tissue from 8 patients was studied
      histopathologically. Neither the white matter hyperintensity scores nor the
      number of focal lesions on magnetic resonance images were associated with the
      presence of an epsilon4 allele. Nor was a correlation found between the number
      and type of plaques and the apolipoprotein E genotype. All patients had severe
      amyloid angiopathy in all cortical areas investigated. This study showed that the
      apolipoprotein E genotype does not modulate amyloid-related structural lesions in
      hereditary cerebral hemorrhage with amyloidosis of the Dutch type.

PMID- 9153537
TI  - Minocycline in rheumatoid arthritis.

PMID- 9153538
TI  - Oral contraceptives and systemic lupus erythematosus.

PMID- 9153539
TI  - Past use of oral contraceptives and the risk of developing systemic lupus
      erythematosus.
AB  - OBJECTIVE: To examine the relationship between past use of oral contraceptives
      (OCs) and development of systemic lupus erythematosus (SLE). METHODS: Prospective
      cohort study of 121,645 women who were followed up every 2 years between 1976 and
      1990 as part of the Nurses' Health Study. Women were classified as never users or
      past users of OCs based on self-report. Incidence of SLE was defined by 1) strict
      American College of Rheumatology (ACR) classification criteria (> or = 4 ACR
      criteria), 2) > or = 4 ACR criteria and any physician's diagnosis, 3) > or = 4
      ACR criteria and diagnosis by an ACR-certified rheumatologist, 4) > or = 3 ACR
      criteria, or 5) diagnosis by a physician even if the patient did not meet the ACR
      criteria. RESULTS: Compared with never users of OCs, and after adjusting for age
      and ever use of postmenopausal hormones, the relative risk (95% confidence
      interval [95% CI]) for the incidence of SLE in the women who had definite cases
      of SLE (> or = 4 ACR criteria) (n = 99) was 1.4 (0.9-2.1) for past users of OCs.
      Using the most stringent case definition (ACR criteria plus a diagnosis of SLE by
      an ACR member) (n = 58), the relative risk for past users compared with never
      users was 1.9 (95% CI 1.1-3.3). No relationship was observed between duration of
      OC use or time since first use and the risk of developing SLE. CONCLUSION: Past
      use of OCs was associated with a slightly increased risk of developing SLE. The
      decision to use hormonal contraception must be individualized, but the small
      absolute risk observed for the development of SLE in white women should not be a
      dominant factor in the decision.

PMID- 9153540
TI  - The reliability of the Systemic Lupus International Collaborating
      Clinics/American College of Rheumatology Damage Index in patients with systemic
      lupus erythematosus.
AB  - OBJECTIVE: To test the reliability of the Systemic Lupus International
      Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index
      and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in the
      assessment of patients with SLE. METHODS: Ten patients with SLE, representing a
      spectrum of damage and activity, were included. Each patient was examined by 6 of
      10 physicians from 5 countries, representing 10 lupus clinics. The SLICC/ACR
      Damage Index was used to assess accumulated damage, and the SLEDAI was used to
      assess disease activity. The order of the patients and physicians was randomized
      according to a Youden square design. RESULTS: The SLICC/ACR Damage Index detected
      differences among patients (P < 0.001). There was no detectable observer
      difference (P = 0.933), and there was no order effect (P = 0.261). Similar
      results were obtained with the SLEDAI. There was concordance in the SLICC/ACR
      Damage Index among observers, despite a wide spectrum of disease activity
      detected by the SLEDAI. CONCLUSION: Physicians from different centers are able to
      assess patients with SLE in a reproducible way, using the SLEDAI to assess
      disease activity and the SLICC/ACR Damage Index to assess accumulated damage.

PMID- 9153541
TI  - In situ expression of B7 and CD28 receptor families in skin lesions of patients
      with lupus erythematosus.
AB  - OBJECTIVE: To examine the expression of costimulatory molecules of the B7 and
      CD28 receptor families in active skin lesions of patients with systemic lupus
      erythematosus (SLE), subacute cutaneous lupus erythematosus (SCLE), and chronic
      discoid lupus erythematosus (CDLE). METHODS: The in situ expression of B7-1, B7
      2, BB-1, and CD28 was studied by immunohistochemistry, and B7-1 and B7-2 RNA
      expression was examined by reverse transcription-polymerase chain reaction.
      RESULTS: Only in lesional skin from SLE, SCLE, and CDLE patients did dermal and
      epidermal antigen-presenting cells (APC) express B7-1 and B7-2, particularly when
      in apposition to CD28+ T cells. These B7-1+ and B7-2+ APC bound CTLA-4 fusion
      protein. In lesional (but not in nonlesional) skin, keratinocytes expressed BB-1.
      The majority of infiltrating T cells were CD28+. B7-1 and B7-2 RNA were expressed
      in lesional skin from SLE, SCLE, and CDLE patients; when dermis was separated
      from epidermis, only faint B7-1 and B7-2 RNA signals were detectable in the
      epidermis, indicating that dermal but not epidermal cells were the major source
      of B7-1 and B7-2 RNA. During treatment, both B7-1 and B7-2 protein and RNA
      expression were reduced. CONCLUSION: These in situ findings suggest that
      costimulation via the B7-CD28 pathway may be important for the generation and/or
      propagation of T cell activity in skin lesions of humans with lupus
      erythematosus. Thus, the manipulation of this pathway (e.g., by CTLA-4 fusion
      protein) could be an important target for the development of future therapies for
      LE.

PMID- 9153542
TI  - Decreased T cell response to anti-CD2 in systemic lupus erythematosus and
      reversal by anti-CD28: evidence for impaired T cell-accessory cell interaction.
AB  - OBJECTIVE: To assess the ability of T cells from patients with systemic lupus
      erythematosus (SLE) to respond to a mitogenic combination of anti-CD2 monoclonal
      antibodies (MAb), and to learn the molecular basis of the documented defect.
      METHODS: Peripheral blood mononuclear cell (PBMC) populations from individuals
      with SLE and paired controls were stimulated in vitro with anti-CD2, and the
      proliferative response was compared with that evoked by stimulation with
      phytohemagglutinin (PHA) and anti-CD3. Surface markers on lymphocyte populations
      were assessed by flow cytometry after staining with specific MAb. RESULTS: The
      proliferative response to anti-CD2 was decreased to a greater extent than was the
      response to anti-CD3 or PHA in SLE patients. This defect was found in
      approximately one-half of the patients examined, was not associated with disease
      activity, and was maintained upon repeated testing. Since either monocytes or
      resting B cells can serve as accessory cells for T cells following activation by
      anti-CD2, we examined the T cell response after depletion of adherent cells. In
      approximately two-thirds of the individuals with a decreased response, depletion
      of monocytes or substitution of monocytes with allogeneic, resting B cells from
      normal donors corrected the defect. The addition to PBMC of anti-CD28, but not of
      a neutralizing antibody to interleukin-10, largely reversed the anti-CD2
      proliferative defect. Significantly fewer CD8+ T cells expressed CD28 in SLE, and
      this defect was also documented, to a lesser extent, in CD4+ cells. CONCLUSION:
      This study provides evidence that some functional T cell defects in SLE may be
      due, at least in part, to decreased CD28-mediated costimulatory activity
      following the interaction of T cells with conventional accessory cells.

PMID- 9153543
TI  - Thrombosis in primary antiphospholipid syndrome: a pivotal role for monocyte
      tissue factor expression.
AB  - OBJECTIVE: The antiphospholipid syndrome (APS) is a disorder of recurrent
      thrombosis, pregnancy loss, and thrombocytopenia associated with the production
      of anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC). The mechanisms
      of thrombus formation remain unknown. Tissue factor (TF), an inducible cell
      glycoprotein, is a major initiator of coagulation in vivo. The present study was
      therefore undertaken to investigate TF expression and procoagulant activity on
      monocytes from patients with primary APS and its correlation with thrombotic
      events. METHODS: Three groups of patients were studied: group 1 comprised 23
      primary APS patients with thrombosis, group 2 consisted of 10 primary APS
      patients without thrombosis, and group 3 contained 20 patients with thrombosis
      but without antiphospholipid antibodies. Twenty age- and sex-matched healthy
      blood donors were used as controls (group 4). Anticardiolipin antibodies were
      measured by enzyme-linked immunosorbent assay (ELISA) and LAC by standard
      methodology. Cell surface expression of TF on monocytes was assessed by flow
      cytometry. The amount of TF in cell lysates (TF(Ag)) and soluble TF(Ag) plasma
      levels were analyzed by ELISA, and the TF-related procoagulant activity (PCA-TF)
      on intact cells and cell lysates by a chromogenic assay. Levels of the cytokines
      that influence TF production, i.e., tumor necrosis factor alpha (TNF alpha) and
      interleukin-1beta (IL-1beta), were determined by ELISA. RESULTS: Cell surface
      expression of TF was increased in group 1 (mean +/- SEM 50.2 +/- 4% positive
      cells) compared with group 2 (14.6 +/- 1.6%), group 3 (16.8 +/- 3.7%), and group
      4 (14.1 +/- 1.6%). TF(Ag) levels were also elevated in group 1 (215.8 +/- 11.2
      pg/10(6)) compared with group 2 (150.8 +/- 15.2), group 3 (101.4 +/- 14.8), and
      group 4 (80.32 +/- 5.5). PCA-TF on intact cells and cell lysates was
      significantly increased in group 1 (148.8 +/- 16.3 units/10(5) lysate cells,
      compared with 54.5 +/- 11.5, 38.6 +/- 9.7, and 22.5 +/- 3.1 in groups 2, 3, and
      4, respectively). Among group 1 patients, there was a significant increase in the
      degree of TF expression in those positive for IgG aCL, but not in those positive
      for IgM aCL or LAC. TNF alpha and IL-1beta plasma levels did not differ
      significantly between any of the groups. CONCLUSION: These results suggest that
      monocyte TF expression is directly involved in the pathogenesis of thrombotic
      complications in patients with the primary APS.

PMID- 9153544
TI  - Treatment of early rheumatoid arthritis with minocycline or placebo: results of a
      randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To determine if minocycline is an effective therapy for seropositive
      rheumatoid arthritis (RA) when used within the first year of disease. METHODS:
      The Rheumatoid Arthritis Investigational Network enrolled 46 patients with RA of
      <1 year duration into a 6-month study of minocycline (100 mg twice daily) versus
      placebo. All patients were rheumatoid factor positive. The primary end point of
      the study was successful completion of 6 months of treatment with no drug
      toxicity while maintaining 50% improvement in composite symptoms of arthritis.
      RESULTS: Eighteen of the 46 patients who were enrolled met 50% improvement
      criteria at 3 months, and maintained at least a 50% improvement for 6 months with
      no significant drug toxicity. Among them were 15 of the 23 patients (65%) treated
      with minocycline and 3 of 23 patients (13%) treated with placebo (P < 0.001).
      CONCLUSION: In patients with early seropositive RA, therapy with minocycline is
      superior to placebo.

PMID- 9153545
TI  - Repeat treatment of rheumatoid arthritis patients with a murine anti
      intercellular adhesion molecule 1 monoclonal antibody.
AB  - OBJECTIVE: To assess the safety and efficacy of a second course of treatment with
      a murine monoclonal antibody (MAb) to intercellular adhesion molecule 1 (ICAM-1;
      CD54) in active rheumatoid arthritis (RA). METHODS: In an open-label study, 8
      patients who had previously received a course of anti-ICAM-1 MAb received a
      second course. RESULTS: The second course of therapy was associated with adverse
      effects suggestive of immune complex formation. Such adverse effects were not
      seen during the initial course of therapy. Clinical efficacy associated with the
      second course of therapy was less than that observed in the first course.
      CONCLUSION: Repeated courses of therapy with a murine MAb to ICAM-1 would
      probably not be a useful therapeutic strategy in patients with RA, probably
      because of its immunogenicity.

PMID- 9153546
TI  - Polymorphism of the HLA-DMA and DMB genes in rheumatoid arthritis.
AB  - OBJECTIVE: To determine whether the HLA-DMA and DMB genes, whose encoded
      molecules are involved in HLA class II-restricted antigen presentation,
      contribute to the genetic susceptibility to rheumatoid arthritis (RA). METHODS:
      One hundred ninety-one RA patients, 147 control subjects, and 218 HLA-DRB1
      genotype-matched control subjects were oligotyped for DMA and DMB genes. RESULTS:
      DMA*0103 and DMB*0104 were significantly increased in the RA patients compared
      with the randomly selected and the matched controls, thus indicating a direct
      influence of the DM genes. After stratification of the patients and matched
      controls according to DRB1 genotypes, only DMA*0103 was increased in the RA
      patients with DRB1*01, as well as in the patients negative for the RA
      susceptibility DR alleles. CONCLUSION: Our results suggest that DMA*0103 could
      play an additional role in the genetic susceptibility to RA.

PMID- 9153547
TI  - Henoch-Schonlein purpura in adulthood and childhood: two different expressions of
      the same syndrome.
AB  - OBJECTIVE: To assess the possible differences between children (< or = 20 years)
      and adults (> 20 years) with Henoch-Schonlein purpura (HSP). METHODS: A
      retrospective study of an unselected population of patients with HSP who
      presented to our teaching hospital between 1975 and 1994. Patients were
      classified as having HSP according to the criteria proposed by Michel et al.
      RESULTS: Following the above-mentioned criteria, 162 white patients (113 male and
      49 female) were classified as having HSP; 46 of the patients were adults (mean +/
      SD age 53.2 +/- 16.9 years) and 116 were children (6.9 +/- 3.1 years). We were
      unable to identify any precipitating event in 72% of the adults and 66% of the
      children. The frequency of previous drug treatment, primarily antibiotics or
      analgesics, was similar in both groups, whereas previous upper respiratory tract
      infection was more frequent among the children (P < 0.02). At symptom onset,
      cutaneous lesions were the main clinical manifestation in both groups. However,
      adults had a lower frequency of abdominal pain (P < 0.008) and fever (P < 0.01),
      and a higher frequency of joint symptoms (P < 0.001). During the clinical course,
      adults had more frequent (P < 0.001) and severe renal involvement. An increased
      erythrocyte sedimentation rate was also more frequent in the adults (P < 0.001).
      Adults required more aggressive therapy, consisting of steroids (P < 0.002)
      and/or cytotoxic agents (P < 0.001). The outcome was relatively good in both age
      groups, with complete recovery in 107 children (93.9%) and in 33 adults (89.2%)
      after a mean +/- SD followup of 19.4 +/- 27.7 (median 12) and 21.8 +/- 33.5
      (median 15) months, respectively. CONCLUSION: In adulthood, HSP, as defined by
      the criteria proposed by Michel et al, represents a more severe clinical
      syndrome, with a higher frequency of renal involvement. However, the final
      outcome of HSP is equally good in patients of both age groups.

PMID- 9153548
TI  - Cytokine production in muscle tissue of patients with idiopathic inflammatory
      myopathies.
AB  - OBJECTIVE: To study cytokine expression in muscle tissues of patients with
      inflammatory myopathies and to compare the profiles of patients with polymyositis
      (PM), inclusion body myositis (IBM), and dermatomyositis (DM). METHODS: We
      performed indirect immunohistochemistry studies of muscle tissue sections with a
      panel of 16 different cytokine-specific monoclonal antibodies, directed against
      interleukin-1alpha, (IL-1alpha), IL-1beta, IL-1 receptor antagonist (IL-1Ra), IL
      2, IL-3, IL-4, IL-6, IL-8, IL-10, IL-13, interferon-gamma (IFN gamma), tumor
      necrosis factor alpha (TNF alpha), granulocyte-macrophage colony-stimulating
      factor (GM-CSF), transforming growth factor beta1 (TGF beta1), TGF beta2, and TGF
      beta3 in 5 untreated patients each with PM, DM, and IBM and in 4 normal controls.
      Fresh frozen muscle tissue sections were fixed in formaldehyde before the
      procedure. The use of saponin as a detergent to permeabilize the cell membranes
      enabled identification of intracellular cytokine production. RESULTS: The most
      prominent finding was the expression of IL-1alpha observed in all patients but in
      none of the normal controls. In all patients with PM, DM, and IBM, IL-1alpha was
      expressed in endothelial cells of capillaries, arterioles, and venules in areas
      surrounded by inflammatory cells, and also in areas with no or scarce
      inflammatory cells in both endomysium and perimysium. Furthermore, IL-1alpha was
      also expressed in mononuclear inflammatory cells in all 15 cases. IL-1beta was
      observed in inflammatory cells in 10 of the 15 patients but, in contrast to IL
      1alpha, it was not expressed in blood vessel walls. TGF beta1, TGF beta2, and TGF
      beta3 were strongly positive in all 15 patients, but only scattered cells were
      positive in the normal controls. The remaining cytokines were observed only in
      relatively few cells and only in occasional patients (although the patients were
      selected for the presence of large infiltrates), and in none of the controls. The
      patterns were similar in PM, DM, and IBM. CONCLUSION: Cytokine expression in
      muscle tissue of patients with inflammatory myopathy is dominated by IL-1alpha,
      IL-1beta, and TGF beta1-3. The predominant IL-1alpha expression in the blood
      vessels indicates an importance of the endothelial cells in the inflammatory
      process in PM, IBM, and DM. A sustained, local release of T cell-derived
      cytokines may not be a requirement for tissue injury in the inflammatory
      myopathies. There does not appear to be a qualitative difference in cytokine
      expression patterns in PM, IBM, and DM.

PMID- 9153549
TI  - Role of nitric oxide in Sjogren's syndrome.
AB  - OBJECTIVE: To measure levels of salivary nitrite (NO2-) and to localize nitric
      oxide synthases (NOS) in the labial salivary glands (LSGs) of patients with
      Sjogren's syndrome (SS). METHODS: NO2- was measured by the Griess reaction. LSGs
      were analyzed using NADPH-diaphorase histochemical and immunohistochemical
      studies to determine the constitutive NOS (neuronal [ncNOS] and endothelial
      [ecNOS]) and inducible NOS (iNOS) isoforms. RESULTS: The NO2- concentration (mean
      +/- SEM 307 +/- 51 microM versus 97 +/- 16 microM; P < 0.05) and output (166 +/-
      46 nmoles/minute versus 37 +/- 7 nmoles/minute) were increased in SS patients
      compared with healthy control subjects. NADPH-diaphorase was found in some nerve
      fibers and endothelial cells, and, in SS, was found in myoepithelial, acinar, and
      ductal epithelial cells, but in only a few inflammatory cells. In SS, ncNOS
      immunoreactive nerve fibers were sparse and ecNOS was found in a minority of the
      CD31-positive vascular endothelial cells and acinar cells, whereas iNOS was
      localized in myoepithelial, acinar, and ductal epithelial cells, often together
      with tumor necrosis factor alpha. CONCLUSION: Nitrite was found in normal human
      saliva. NO produced by ncNOS probably acts as a nonadrenergic, noncholinergic
      neurotransmitter, whereas that produced by ecNOS exerts a vasodilatory effect. SS
      patients had increased NO2- concentrations, with most of the superfluous salivary
      NO being produced not by the immigrant inflammatory cells, but rather, by the
      resident salivary gland cells. NO may contribute to inflammatory damage and
      acinar cell atrophy in SS.

PMID- 9153550
TI  - The outcome of bacterial arthritis: a prospective community-based study.
AB  - OBJECTIVE: To assess the outcome and adverse prognostic factors of bacterial
      arthritis (BA). METHODS: In a prospective community survey of BA, data were
      collected at the time of diagnosis and at a mean of 2 years later. A poor patient
      outcome was defined as death due to BA or severe overall functional
      deterioration. A poor joint outcome was defined as amputation, arthrodesis,
      prosthetic surgery, or severe functional deterioration. Possible prognostic
      factors were analyzed by univariate analysis. RESULTS: BA was diagnosed in 154
      patients, 121 adults and 33 children. One-half of the adults had a preexisting
      joint disease and 29% of the infected joints contained synthetic material. The
      patient outcome was poor in 21% of all patients, and the joint outcome was poor
      in 33% of the surviving patients. Adverse prognostic factors were an older age,
      preexisting joint disease, and an infected joint containing synthetic material.
      These factors were interrelated. There was no association between a poor outcome
      and young age, comorbidity, immunosuppressive medication, functional class,
      multiple infected joints, type of microorganism, or treatment delay. CONCLUSION:
      BA had a poor outcome in almost one-half of the patients. Patients who were
      older, had a preexisting joint disease, and/or had an infected joint containing
      synthetic material had the poorest prognosis.

PMID- 9153551
TI  - Prevention of murine collagen-induced arthritis in the knee and ipsilateral paw
      by local expression of human interleukin-1 receptor antagonist protein in the
      knee.
AB  - OBJECTIVE: To determine the efficacy of local human interleukin-1 receptor
      antagonist (HuIL-1Ra) gene therapy in murine collagen-induced arthritis (CIA).
      METHODS: DBA/1 mice were immunized against bovine type II collagen. Before the
      onset of arthritis, NIH/3T3 fibroblasts transfected with pMFG-IRAP were
      transplanted into the knee cavity. Normal NIH/3T3 cells served as controls. Paws
      were evaluated macroscopically for redness, swelling, and deformities during the
      course of arthritis. Swelling of the knee joints was measured by external gamma
      counting of 99mtechnetium accumulation in the joint. Paws and knee joints were
      dissected and processed for histologic studies to evaluate inflammation and
      cartilage destruction. RESULTS: The NIH/3T3 fibroblasts survived in the joint
      cavity of DBA mice for at least 7 days. The transduced cells expressed
      immunoreactive and bioactive HuIL-1Ra in the knee joint, and produced sufficient
      amounts to block the effect of 1 ng of recombinant murine IL-1alpha on
      chondrocyte proteoglycan synthesis. The onset of CIA was almost completely
      prevented in knee joints containing HuIL-1Ra-producing cells, whereas joints
      containing normal cells showed severe inflammation and destruction of cartilage.
      Moreover, onset of CIA in the draining joints (ipsilateral paws) of the HuIL-1Ra
      gene-bearing knees was also prevented. CONCLUSION: Local production of HuIL-1Ra
      in the knee was able to ameliorate the effects of IL-1 on cartilage and could
      prevent the onset of CIA not only in that knee, but also in the "draining" paw.
      This indicates the feasibility of gene transfer as a therapeutic approach to
      modulating arthritis.

PMID- 9153553
TI  - Reduction in the incidence and severity of collagen-induced arthritis in DBA/1
      mice, using exogenous dehydroepiandrosterone.
AB  - OBJECTIVE: This study examined the effect of exogenous dehydroepiandrosterone
      (DHEA) on the onset, incidence, and severity of collagen-induced arthritis (CIA).
      METHODS: DHEA was administered subcutaneously prior to arthritis induction in
      DBA/1 mice, and the severity of the subsequent arthritis was monitored. Serum
      levels of total IgG and IgG isotype-specific anti-murine type II collagen were
      measured. RESULTS: Repeated administration of DHEA during arthritis induction
      delayed the onset and decreased the severity of arthritis in male and female
      DBA/1 mice. DHEA failed to have an observable effect on established arthritis.
      IgG isotype autoantibody levels were found to be decreased in the sera of DHEA
      treated mice. CONCLUSION: Administration of exogenous DHEA offered protection
      against the development of CIA. These data support the results of human studies
      in which low DHEA levels have been identified as a potential risk factor for the
      development of rheumatoid arthritis. These findings also highlight DHEA as a
      potential therapy worthy of further investigation.

PMID- 9153552
TI  - In vivo direct gene transfer into articular cartilage by intraarticular injection
      mediated by HVJ (Sendai virus) and liposomes.
AB  - OBJECTIVE: To establish a system for efficient, direct in vivo gene transfer into
      joints. METHODS: A hemagglutinating virus of Japan (HVJ; Sendai virus)-liposome
      suspension containing SV40 large T antigen (SVT) gene was injected
      intraarticularly into knee joints of 6-week-old female Lewis rats. Rats were
      killed at various times for immunohistochemical analysis of the expression of SVT
      gene. RESULTS: The expression of SVT gene was detected immunohistochemically in
      chondrocytes in the superficial and middle zones of articular cartilage in the
      knee joints. The average percentage of SVT-positive cells was estimated to be
      approximately 30% on days 3, 7, 14, and 21 after transfection. Moreover, no
      pathologic change caused by HVJ-liposome injection was observed in the joints.
      CONCLUSION: The transfection frequency and stability of expression recognized in
      this study indicate the possibility of a strategy for treatment of joint
      disorders, including arthritis, using direct gene transfer.

PMID- 9153554
TI  - Direct evidence of high DNA binding activity of transcription factor AP-1 in
      rheumatoid arthritis synovium.
AB  - OBJECTIVE: To investigate the possible activation of transcription factor AP-1 in
      rheumatoid arthritis (RA) and its involvement in the pathogenesis of RA. METHODS:
      Synovial tissues and peripheral blood samples were obtained from 25 patients with
      RA and 5 patients with osteoarthritis (OA) during arthroplasty and synovectomy.
      The synovial tissue was digested with collagenase and separated into adherent and
      nonadherent cells by plastic-adhesion methods. Nuclear extracts obtained from
      each sample were examined by electrophoretic mobility shift assay to determine
      the DNA binding activity of AP-1. The expression of c-fos and c-jun messenger RNA
      (mRNA) was examined by in situ reverse transcription assay. RESULTS: A markedly
      high DNA binding activity of AP-1 was detected in the synovial tissues of RA
      patients, while virtually no activity or only a little activity was observed in
      OA patients. Following separation of adherent and nonadherent cells, the AP-1
      activity was mainly detected in adherent cells, which consisted of synovial cells
      and macrophages. However, the activity was significantly higher in the
      mononuclear cells infiltrating into RA synovium than in RA peripheral blood
      mononuclear cells. The high DNA binding activity of AP-1 in RA correlated with
      the expression of c-fos and c-jun mRNA in situ. Furthermore, AP-1 binding
      activity also correlated with disease activity. CONCLUSION: In RA synovium, AP-1
      DNA binding activity was constitutively up-regulated. These findings suggest that
      AP-1 may play an important role in the pathogenesis of RA, including synovial
      hyperplasia and abnormal immune responses.

PMID- 9153555
TI  - Selective activation of the JNK/AP-1 pathway in Fas-mediated apoptosis of
      rheumatoid arthritis synoviocytes.
AB  - OBJECTIVE: To evaluate the Fas-dependent signaling pathway, we examined the
      involvement of protein tyrosine phosphorylation and the DNA binding activity of
      AP-1 in rheumatoid arthritis (RA) cultured synovial cells. METHODS: The number of
      dead cells was counted after treatment with anti-Fas antibody in the presence of
      protein tyrosine kinase or phosphatase inhibitor. Protein tyrosine
      phosphorylation in synoviocytes after Fas ligation was examined by immunoblot and
      immunoprecipitation analyses. The DNA binding activity of AP-1 was examined by
      electrophoretic mobility shift assay. RESULTS: Treatment with the protein
      tyrosine phosphatase inhibitor, orthovanadate, significantly enhanced the
      apoptosis of RA synoviocytes after Fas ligation. Ligation of the Fas molecule on
      RA synoviocytes induced a rapid tyrosine phosphorylation of JNK (c-Jun amino
      terminal kinase) and formation of the AP-1 transcription factor. CONCLUSION: Our
      results strongly suggest that the JNK/AP-1 signaling pathway is activated during
      the process of Fas-mediated apoptosis of RA synovial cells.

PMID- 9153556
TI  - Induction of apoptosis in peripheral blood lymphocytes following treatment in
      vitro with hydroxychloroquine.
AB  - OBJECTIVE: Defective regulation of apoptosis may be central to the development of
      autoimmune disorders. This study investigated the possibility that the
      antirheumatic effect of hydroxycholoroquine (HCQ) may be achieved by up
      regulation of apoptosis. METHODS: Peripheral blood lymphocytes collected from
      normal controls and patients with systemic lupus erythematosus (SLE) were
      cultured in the presence or absence of a range of concentrations of HCQ. Cells
      undergoing apoptosis were identified by several standard methods, including
      morphologic changes, DNA fragmentation, and flow cytometry. For some experiments,
      lymphocytes were simultaneously stained with antibodies to T cell surface markers
      and with propidium iodide for dual-stain flow cytometric studies. RESULTS: HCQ
      was able to induce apoptosis in peripheral blood lymphocytes in a dose- and time
      dependent manner. HCQ induced these changes in all T cell subpopulations studied.
      There was no significant difference between the controls and patients with SLE in
      terms of the percentage of apoptotic cells detected following treatment with HCQ.
      CONCLUSION: The present study demonstrated that HCQ induces apoptosis in
      peripheral blood lymphocytes, which leads to the speculation that HCQ may exert
      its antirheumatic effect through this mechanism.

PMID- 9153557
TI  - The 52-kd protein as a target of intermolecular spreading of the immune response
      to components of the SS-A/Ro-SS-B/La complex.
AB  - OBJECTIVE: To determine whether immunization of healthy non-autoimmune mice with
      52-kd SS-A/Ro induces a secondary antibody response to other components of the 48
      kd SS-B/La-60-kd SS-A/Ro RNP complex and vice versa, since anti-52-kd antibodies
      have been invariably linked to these antigens in patients with Sjogren's syndrome
      and in mothers whose children have neonatal lupus. METHODS: Female BALB/c mice
      were immunized with 100 microg of 6xHis recombinant human 48-kd SS-B/La, 52-kd SS
      A/Ro, or 60-kd SS-A/Ro proteins, or the 6xHis polypeptide control, each purified
      by Ni2+ affinity chromatography. Mice subsequently received booster injections
      with 50 microg of the same antigen every 10-21 days. Immune responses were
      measured by enzyme-linked immunosorbent assay (ELISA), immunoblotting of
      recombinant antigens, and immunoprecipitation of 35S-methionine-labeled in vitro
      translation products. RESULTS: Immunization with 48-kd SS-B/La resulted in anti
      48-kd SS-B/La antibodies within 45 days, followed 10 days later by a secondary
      response to 52-kd SS-A/Ro, as measured by ELISA. Antibody spreading to 60-kd SS
      A/Ro was not detected. Immunization with 52-kd SS-A/Ro resulted in rapid high
      titer anti-52-kd SS-A/Ro responses within 27 days. Spreading to 48-kd SS-B/La
      occurred in only 1 mouse and 60-kd SS-A/Ro was detected in a minority of the mice
      after prolonged antigen exposure. Immunization with 60-kd SS-A/Ro led to anti-60
      kd SS-A/Ro responses within 37 days, followed 3 months later by low-titer anti-48
      kd SS-B/La and anti-52-kd SS-A/Ro antibodies. All primary immune responses were
      confirmed by immunoblotting and immunoprecipitation. While immunoblotting of the
      recombinant proteins revealed reciprocal intermolecular spreading in the majority
      of mice, immunoprecipitation clearly demonstrated that predominant spreading was
      generated after immunization with 48-kd SS-B/La, which consistently resulted in
      antibodies to 52-kd SS-A/Ro. CONCLUSION: The murine responses observed in the
      present study, demonstrating reciprocal intermolecular spreading to 48-kd SS
      B/La, 52-kd SS-A/Ro, and 60-kd SS-A/Ro, support the linkage of 52-kd SS-A/Ro with
      the other proteins, despite their as-yet-undetected association in vivo. The
      marked recruitment of anti-52-kd SS-A/Ro responses elicited by 48-kd SS-B/La may
      provide a lead to exploring the physical interaction, direct or indirect, of 52
      kd SS-A/Ro with the SS-A/Ro-SS-B/La RNP particle and its presentation to the
      immune system. These data should facilitate the establishment of a murine model
      of neonatal lupus.

PMID- 9153559
TI  - Endothelial activation in monosodium urate monohydrate crystal-induced
      inflammation: in vitro and in vivo studies on the roles of tumor necrosis factor
      alpha and interleukin-1.
AB  - OBJECTIVE: There is relatively little direct evidence for the roles of
      interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) in activating
      endothelium in vivo. The aim of this study was to use in vitro and in vivo models
      to investigate the contribution of these cytokines to both E-selectin expression
      and the recruitment of polymorphonuclear cells (PMN) in monosodium urate
      monohydrate (MSU) crystal-induced inflammation. METHODS: MSU crystals were
      incubated with freshly isolated mononuclear cells, after which the harvested
      supernatants were tested for their ability to induce E-selectin expression during
      coculture with human umbilical vein endothelial cells. Subsequent experiments
      were performed with the addition of neutralizing anticytokine
      antibodies/antisera. The role of TNF alpha was then studied in an MSU crystal
      induced monarthritis model, in the presence or absence of anti-TNF alpha (5 mg/kg
      intravenously). 99mtechnetium (99mTc)-labeled PMN cells and (111)indium (111In)
      labeled anti-E-selectin monoclonal antibody (MAb) 1.2B6 were intravenously
      administered 4 hours after intraarticular injection to quantify PMN recruitment
      and E-selectin expression in inflamed joints. RESULTS: MSU crystals were a potent
      stimulus for IL-1 and TNF alpha production by monocytes in vitro, and these
      cytokines fully accounted for MSU crystal-stimulated, monocyte-mediated
      endothelial activation. In the MSU crystal-induced monarthritis model, TNF alpha
      blockade was very effective in suppressing both E-selectin expression and PMN
      emigration into the inflamed joints, as judged by gamma-camera image analysis and
      postmortem tissue counting following the intravenous injection of 99mTc-PMN and
      111In-anti-E-selectin MAb. CONCLUSION: IL-1 and TNF alpha appear to be the only
      factors released by monocytes following incubation with MSU crystals, which
      induce E-selectin expression in vitro. Anti-TNF alpha is effective in suppressing
      endothelial activation and PMN recruitment in vivo E-selectin imaging can be used
      to assess the endothelial response to therapy and may prove useful for clinical
      studies.

PMID- 9153558
TI  - Recognition of chlamydial antigen by HLA-B27-restricted cytotoxic T cells in HLA
      B*2705 transgenic CBA (H-2k) mice.
AB  - OBJECTIVE: The association of reactive arthritis (ReA) with HLA-B27 and the
      presence of bacterial antigen in joints with ReA suggest that bacterial peptides
      might be presented by the HLA-B27 molecule and thus stimulate CD8 T cells. This
      study was performed to investigate the B27-restricted cytotoxic T lymphocyte
      (CTL) response to Chlamydia trachomatis, using the model of HLA-B27 transgenic
      mice. METHODS: CBA (H-2k) mice homozygous for HLA-B*2705 and human beta2
      microglobulin expression were immunized with C trachomatis or with the chlamydial
      57-kd heat-shock protein (hsp57) coupled to latex beads. Cytotoxicity of
      lymphocytes from in vivo-primed transgenic mice was tested against C trachomatis
      infected targets. Blocking experiments were performed with monoclonal antibodies
      (MAb) against class I major histocompatibility complex molecules. RESULTS: A
      Chlamydia-specific lysis of both B27-transfected and nontransfected target cells
      was observed. This response could be inhibited by anti-B27 and anti-H2 MAb. CTL
      from mice immunized with hsp57 were not able to lyse Chlamydia-infected target
      cells, and Chlamydia-specific CTL could not destroy targets loaded with hsp57.
      CONCLUSION: These results suggest the existence of at least 2 CTL populations in
      this mouse model: one recognizing peptide of bacteria-infected cells restricted
      by HLA-B*2705 and the other recognizing peptide of bacteria-infected cells
      restricted by the murine H-2Kk molecule. It does not appear that hsp57 is a major
      target for the CD8 T cell response directed against Chlamydia. This animal model
      opens the way for identifying bacterial epitopes presented by HLA-B27, and might
      thus help to clarify the pathogenesis of B27-associated diseases.

PMID- 9153560
TI  - Transglutaminase activity in aging articular chondrocytes and articular cartilage
      vesicles.
AB  - OBJECTIVE: Transglutaminases (TGases) (E.C. 2.3.2.13) catalyze a
      posttranslational modification of proteins and are associated with
      biomineralization in growth plate cartilage. Type II TGase participates in the
      activation of latent transforming growth factor beta (TGFbeta), a crucial factor
      for both normal cartilage mineralization and the pathologic mineralization that
      results in calcium pyrophosphate dihydrate (CPPD) crystal formation in aging
      articular cartilage. To explore a possible association between TGase levels and
      CPPD crystal formation in mature articular cartilage, TGase activity in articular
      chondrocytes from old and young pigs and in the articular cartilage vesicle (ACV)
      fraction of porcine articular cartilage was examined. In addition, the effects of
      TGase inhibitors on the production of inorganic pyrophosphate (PPi), a process
      necessary for CPPD crystallogenesis, were determined. METHODS: TGase activity was
      measured with a radiometric assay in cultured articular chondrocytes from the
      knee joints of old (3-5 years old) and young (2-6 weeks old) pigs and in the
      ACVs. PPi levels were measured in chondrocyte-conditioned media in the presence
      of TGase inhibitors or control compounds. RESULTS: Levels of TGase activity in
      the cytosolic fraction of old chondrocytes were 7-fold higher than those in
      identically cultured young chondrocytes. The mean +/- SD activity level in the
      membrane fraction of lysed chondrocytes was 6.0 +/- 0.6 units/mg protein in old
      articular chondrocytes and was undetectable in young chondrocytes. In ACVs, the
      mean +/- SD TGase activity level was 1.23 +/- 0.1 units/mg protein. Type II TGase
      protein was present in chondrocyte cytosol and in ACVs. TGase activity was
      increased by TGFbeta to 120% of control values (P < 0.01), and decreased by
      insulin-like growth factor 1 to 80% of control values (P < 0.01). TGase
      inhibitors blocked media accumulation of PPi, an essential precursor of CPPD
      crystal formation, and a sensitive marker of TGFbeta effect. CONCLUSION: These
      data suggest a potential link between TGase activity and processes of pathologic
      biomineralization that result in CPPD crystal formation in aging articular
      cartilage.

PMID- 9153561
TI  - Multiple congenital anomalies associated with weekly low-dose methotrexate
      treatment of the mother.
AB  - This report describes an infant with multiple congenital anomalies born to a 20
      year-old mother with juvenile rheumatoid arthritis who had been taking weekly low
      dose methotrexate (MTX) during the first trimester of pregnancy. The
      abnormalities found were consistent with those associated with maternal ingestion
      of MTX at dosage levels used to induce abortions, i.e., the group of
      abnormalities referred to as the "aminopterin syndrome." Although weekly low-dose
      MTX has been associated with spontaneous abortions, this is, to our knowledge,
      the first case report describing multiple congenital abnormalities consistent
      with MTX embryopathy secondary to weekly low-dose MTX treatment.

PMID- 9153562
TI  - Acute calcific tendinitis of the hip: case report with magnetic resonance imaging
      findings.
AB  - The clinical presentation of acute calcific tendinitis can be quite dramatic.
      This report describes a patient with this entity who had calcification in an
      unusual area, accompanied by abnormalities seen on radiography and magnetic
      resonance imaging. Clinical aspects of acute calcific tendinitis are also
      reviewed. With recognition of this entity, treatment can be initiated promptly,
      with dramatic resolution.

PMID- 9153563
TI  - Intraosseous lipoma.

PMID- 9153564
TI  - Antibodies against p53 in sera from patients with systemic lupus erythematosus
      and other rheumatic diseases.

PMID- 9153565
TI  - Neonatal lupus erythematosus: haplotypic analysis of HLA class II alleles in
      child/mother pairs.

PMID- 9153566
TI  - Safety, efficacy, and mortality in a long-term cohort of patients with rheumatoid
      arthritis taking methotrexate: followup after a mean of 13.3 years.

PMID- 9153567
TI  - Finding a valid model for antineutrophil cytoplasmic antibody-related vasculitis.

PMID- 9153568
TI  - Cytokine expression in the salivary glands of Sjogren's syndrome patients in
      relation to tissue infiltration and lymphoepithelial lesions.

PMID- 9153569
TI  - The synapse between LE sensory neurons and gill motoneurons makes only a small
      contribution to the Aplysia gill-withdrawal reflex.
AB  - The monosynaptic connection between the mechano-sensory neurons in the LE cluster
      and gill motoneurons has been extensively studied and used as a model for the
      gill-withdrawal reflex and its behavioural plasticity. In an attempt to evaluate
      the contribution of this synapse to the behaviour, we used voltage-sensitive dye
      recording to determine the number of activated LE neurons and the number of
      spikes made by each neuron in response to a light touch. In five preparations,
      light touch activated a median of five sensory cells with a median of 1.6 spikes
      per cell. From a comparison of the sizes of the motoneuron synaptic potentials
      elicited by LE spikes and elicited by a light siphon touch, we estimate that the
      LE sensory neurons contribute approximately 5% of the motoneuron synaptic
      potential in response to this touch. This result casts doubt on the validity of
      using this synaptic connection as a model for gill-withdrawal behaviour. Siphon
      nerve recordings reveal the existence of short-latency, low-threshold neurons
      that may provide much of the sensory input in response to a light touch.

PMID- 9153571
TI  - Photoreceptor cells of the pike pineal organ as cellular circadian oscillators.
AB  - In the pike pineal, the rhythm of melatonin (MEL) secretion is driven by a
      population of cellular circadian oscillators, synchronized by the 24 h light/dark
      (LD) cycle. Because the pineal photoreceptor contains both the input and output
      pathways of the clock, this cell is likely to be a cellular circadian system by
      itself. To support this idea, we have dissociated and cultured pike pineal cells
      as well as purified photoreceptors. In culture, the pineal cells reassociated in
      follicles, surrounded by collagen fibres. At the electron microscopic level, they
      appeared well preserved. Total cells consisted mainly of photoreceptors and glia.
      Purified cells corresponded exclusively to photoreceptors. Under LD, MEL
      production was rhythmic. Under constant darkness (DD), the rhythm was well
      sustained for at least six 24 h cycles (tau = 24/27 h) with 1 x 10(6) total
      cells/well or below; with 2 x 10(6) total cells/well, a strong damping occurred
      towards high levels as soon as after the second cycle. At the density of 0.5 x
      10(6) cells/well, purified photoreceptors produced less MEL than an equivalent
      amount of total cells. However, the pattern of the oscillations was similar to
      that observed with 2 x 10(6) total cells, i.e. a damping occurred rapidly.
      Decreasing the density to 0.125 x 10(6) photoreceptors/well resulted in a loss of
      homogeneity among replicates. The production of melatonin by single
      photoreceptors was monitored by means of the reverse haemolytic plaque assay.
      Both under LD and under DD, the number of photoreceptors releasing melatonin was
      higher during the (subjective) dark than during the (subjective) light. The
      results provide strong support to the idea that the pike pineal photoreceptor is
      a cellular circadian system. Expression of the oscillations seemed to depend on
      several factors, including cell to cell contacts between photoreceptors. There is
      indication that also MEL and glia might be involved.

PMID- 9153570
TI  - Experience-dependent facilitating effect of corticosterone on spatial memory
      formation in the water maze.
AB  - Stress-related adrenal steroid hormones modulate brain and cognitive function.
      Electrophysiological studies, including primed burst potentiation and long-term
      potentiation, have indicated concentration-dependent inverted U-shape effects of
      corticosterone in hippocampal function and plasticity. Here, we explored the role
      of corticosterone in the consolidation and long-term retrieval of spatial
      learning in the Morris water maze task in rats. We postulated that corticosterone
      actions might be experience-dependent with regard to stimulus intensity, such as
      differential water temperatures. Indeed, rats trained at 19 degrees C showed a
      quicker rate of acquisition and better long-term retention than rats trained at
      25 degrees C water. In addition, post-training corticosterone levels, on the
      first training day, were significantly higher in rats in the 19 degrees C group
      than in the 25 degrees C group. Performance of rats trained at 25 degrees C, but
      not at 19 degrees C, water was improved by injecting them i.p. with
      corticosterone immediately after each training session. Thus, the effect of
      exogenously administered corticosterone appears to be experience-dependent, with
      the experience-induced corticosterone concentrations as a critical factor
      determining the cognitive consequences of steroid treatment. Therefore, this work
      indicates a facilitating corticosterone action, during the post-training period,
      on the neural mechanisms determining the strength of information storage under
      acute, physiological conditions.

PMID- 9153572
TI  - Visual activation in alpha-chloralose-anaesthetized cats does not cause lactate
      accumulation in the visual cortex as detected by [1H]NMR difference spectroscopy.
AB  - The hypothesis that neuronal activation results in lactate accumulation due to
      mismatch between glucose and oxygen consumption was tested in the cat model of
      visual activation by monitoring cerebral metabolism with localized 1H nuclear
      magnetic resonance spectroscopy (MRS). Adult cats were anaesthetized with alpha
      chloralose, paralysed and mechanically ventilated. Visual evoked potentials
      measured over the occipital cortex showed maximal amplitude at 2 Hz stimulation,
      but the latencies of the early cortical potentials, N1 and P1, were independent
      of stimulation frequency. High signal-to-noise ratio, short echo time volume
      selected [1H]MRS was used to monitor cerebral lactate with a temporal resolution
      of 70 s. Difference proton spectroscopy unambiguously showed no lactate peak in
      the visual cortex during visual activation at stimulation frequencies ranging
      from 1 to 16 Hz. Absence of change in lactate concentration during visual
      stimulation was confirmed by averaging all the spectra acquired during activation
      and subtracting them from reference spectra collected in darkness, a procedure
      that had a calculated lactate detection limit of 0.17 mM. We also reduced the O2
      in the inspired air to 13%, which decreased pO2 from 94.5 +/- 8.9 to 47.0 +/- 6.8
      mmHg, during visual stimulation at 2 or 4 Hz. At this low PO2 level, visual
      stimulation did not cause lactate accumulation in the visual cortex, however. The
      present data show that neuronal activation to this degree in the cat brain is not
      associated with aerobic lactate production to an extent that can be detected with
      1H MRS.

PMID- 9153573
TI  - Localization of CAM II kinase-alpha, GAD, GluR2 and GABA(A) receptor subunit
      mRNAs in the human entorhinal cortex.
AB  - The human entorhinal cortex (ERC) is an important relay between neocortical
      association areas and the hippocampus. Pathology in this area, including
      disturbances in its unique cytoarchitecture and alterations in neurotransmitter
      receptor binding, has been implicated in several neuropsychiatric disorders but
      details of the patterns of gene expression for molecules involved in the major
      neurotransmitter systems in this cortex have been lacking. We used in situ
      hybridization histochemistry to localize the mRNAs for several proteins which are
      involved in excitatory and inhibitory neurotransmission in the human ERC.
      Labelling of mRNA for a glutamate receptor subunit (GluR2) and for a marker of
      glutamatergic cortical neurons (alpha type II calcium/calmodulin-dependent
      protein kinase) were distributed in a laminar manner which matched the cellular
      packing seen on the Nissl sections, with particularly high levels of labelling in
      the layer II (pre-alpha) cell clusters characteristic of this cortex. Cells
      labelled for the mRNA of 67 kDa glutamic acid decarboxylase, the synthesizing
      enzyme of GABA, were distributed diffusely throughout all layers, not
      concentrated in the cell clusters, and were present in higher numbers in layer
      III. The labelling of mRNAs for the alpha1, beta2 and gamma2 subunits of the
      GABA(A) receptor, however, was distributed in a laminar pattern similar to that
      for GluR2 and CAM II kinase mRNAs, implying a high concentration of inhibitory
      synapses on the excitatory cells which express these mRNAs.

PMID- 9153574
TI  - Regulation of quantal transmitter secretion by ATP and protein kinases at
      developing neuromuscular synapses.
AB  - The effects of endogenously released ATP on the maturation of developing
      neuromuscular synapses were investigated in Xenopus nerve-muscle co-cultures. The
      potentiating action of ATP (1 mM) on spontaneous acetylcholine release was
      inhibited by P2-purinoceptor antagonists suramin (0.3 mM) and reactive blue 2 (RB
      2, 3 microM) in day 1 cultures. Bath application of suramin (10 microM) or RB-2
      in day 1 cultures and prolonged treatment for 2 days dramatically decreased the
      amplitude of both spontaneous synaptic currents (SSCs) and evoked synaptic
      currents (ESCs) in the same cultures on day 3. Chronic treatment with 8
      cyclopentyltheophylline (4 microM) or 6-cyano-2,3-dihydroxy-7-nitroquinoxaline
      (CNQX, 10 microM), P1-purinoceptor and glutamate receptor antagonists
      respectively, did not exert such an inhibitory effect. Chronic treatment with
      suramin or RB-2 for 2 days had no significant effect on the amplitude of either
      iontophoretic acetylcholine-induced whole-cell currents or single acetylcholine
      channel measurements in 3-day-old cultured myocytes. In addition, prolonged
      treatment for 2 days with various kinase inhibitors such as H-8 (10 microM), KN
      62 (5 microM) and H-7 (10 microM) also decreased the amplitudes of both
      spontaneous and evoked synaptic currents in natural synapses, but not those of
      iontophoretic acetylcholine-induced currents. Furthermore, suramin and these
      protein kinase inhibitors also decreased the amplitude of spontaneous synaptic
      currents in manipulated synapses of 'vacated' nerve terminals. The results
      suggest that endogenously released ATP, acting in concert with various protein
      kinases, is involved in the maintenance and/or development of the quantum size of
      synaptic vesicles at embryonic neuromuscular synapses.

PMID- 9153575
TI  - Activation by cutaneous or visceral noxious stimulation of spinal neurons
      projecting to the medullary dorsal reticular nucleus in the rat: a c-fos study.
AB  - The involvement of spinal neurons in the transmission of cutaneous and visceral
      nociceptive input to the medullary dorsal reticular nucleus was studied. Rats
      were injected with cholera toxin subunit B in the left dorsal reticular nucleus
      and subjected 4 days later to noxious mechanical, thermal or chemical stimulation
      of the proximal internal aspect of the left thigh, or to chemical stimulation of
      the urinary bladder. Sections of spinal segments T13-L3 were processed
      immunocytochemically for cholera toxin subunit B and Fos protein. The percentage
      of double-labelled cells in the population of Fos-positive cells was higher in
      lamina I (1-4%) than in deeper laminae (0-0.7%) following all stimuli. The
      percentage of double-labelled cells in the population of retrogradely labelled
      cells was 30-53% in lamina I and 0-5% in laminae III-X. Visceral stimulation
      activated more retrogradely labelled lamina I cells than any kind of cutaneous
      stimulation. Pyramidal cells were activated in higher numbers than multipolar and
      flattened cells after thermal cutaneous or visceral stimulation, and in lower
      numbers than multipolar cells after mechanical stimulation. These results suggest
      that, in the experimental conditions used, spinal cord cells conveying noxious
      input to the dorsal reticular nucleus are concentrated in lamina I. They further
      indicate that the spinal-dorsal reticular nucleus pathway plays a major role in
      the transmission of nociceptive visceral input, and point to the preferential
      involvement of pyramidal cells in cutaneous thermal and visceral processing.

PMID- 9153576
TI  - Locomotor-related presynaptic modulation of primary afferents in the lamprey.
AB  - Presynaptic modulation of sensory afferent transmission during rhythmic motor
      activity was investigated in the lamprey spinal cord in vitro. Intracellular
      recordings were performed from the somata and axons of the glutamatergic sensory
      neurons from the skin (dorsal cells) during locomotor activity induced by N
      methyl-D-aspartate (NMDA). Dorsal cells were phasically depolarized during each
      ipsilateral ventral root burst. In some soma recordings no or only small
      amplitude depolarizations were seen, although intracellular recording of their
      axons revealed the existence of large depolarizations, suggesting that the input
      synapses are located on the axons. The amplitude of the depolarizations increased
      during intracellular injection of hyperpolarizing current. The amplitude of the
      depolarizations increased when the frequency of the locomotor rhythm was
      increased by elevating the NMDA concentration. The depolarizations were not
      blocked by specific GABA(A) (bicuculline) or GABA(B) (phaclofen and saclofen)
      antagonists. To investigate whether the phasic depolarization may influence the
      monosynaptic excitatory transmission to giant interneurons, the amplitude of the
      monosynaptic excitatory postsynaptic potential (EPSP) was compared between the
      onset of the ipsilateral locomotor burst and the burst mid-point. The compound
      monosynaptic EPSP evoked from dorsal column was significantly smaller during the
      peak depolarization than at burst onset. The reduction of the amplitude of the
      EPSPs was not associated with any change of the membrane potential or input
      resistance of the giant interneurons, suggesting that this effect is mediated by
      a presynaptic mechanism. Phase-dependent effects were also seen on burst and
      cycle duration following dorsal column stimulation. Thus, the locomotor-related
      depolarizations in dorsal cell axons may represent a mechanism for a phasic gain
      control of sensory transmission during fictive locomotion.

PMID- 9153577
TI  - Analysis of the ion channel complement of the rat oligodendrocyte progenitor in a
      commonly studied in vitro preparation.
AB  - We have analysed the ion channel complement of the oligodendrocyte-type 2
      astrocyte (O-2A) glial cell progenitor obtained from the commonly studied
      neonatal rat mixed brain preparation. Ionic currents, in O-2A progenitors
      identified on both morphological and immunological grounds, were recorded using
      the whole-cell variant of the patch-clamp technique. The cells had an average
      resting membrane potential close to -50 mV and fired single action potentials in
      response to suprathreshold current injections. Using voltage-clamp methods we
      were able to identify and characterize a voltage-activated TTX-sensitive Na+
      current, two classes of voltage-activated outward K+ currents, an inactivating
      inwardly rectifying K+ current, a voltage-activated Cl- current and at least
      three classes of Ca2+ current.

PMID- 9153578
TI  - Molecular and functional diversity at synapses of individual neurons in vitro.
AB  - We have quantified activity-dependent uptake of the fluorescent dye FM1-43 in
      combination with immunocytochemistry for synaptic vesicle-associated proteins
      (SVPs) at individual synapses in primary cultures of rat cortical neurons. We
      show that expression of synaptic proteins is highly variable and that the levels
      of synaptophysin (p38), synapsin I and sv2, but not synapsin II, correlate with
      the extent of FM1-43 labelling at synapses. The data indicate that SVP levels
      affect the uptake of FM1-43 with different efficacy (p38 > synapsin I > sv2 or
      synapsin II). We also found that the relative levels of SVPs vary at individual
      boutons of single neurons grown in isolation, which indicates that differential
      regulation of specific SVPs may contribute to the selective modulation of
      activity at synapses of the same neuron.

PMID- 9153579
TI  - Zinc blocks acetylcholine release but not vesicle fusion at the Torpedo nerve
      electroplate junction.
AB  - The combined effects of Zn2+ treatment and nerve stimulation were studied on
      cholinergic synapses of the Torpedo marmorata electric organ. Incubation of small
      pieces of electric tissue in 250 microM ZnCl2 for 2 h irreversibly blocked
      synaptic transmission by inhibiting the release of acetylcholine. This treatment,
      however, did not cause any significant fine structural alteration in the nerve
      electroplate junctions. Preparations treated with Zn2+ were submitted to
      electrical stimulation. In spite of the fact that no transmitter was released,
      stimulation resulted in the accumulation of calcium in the tissue, and in marked
      ultrastructural changes. The density of synaptic vesicles was significantly
      reduced and many of the remaining vesicles were found in close proximity to the
      presynaptic membrane. Images of vesicles fused with the plasmalemma were
      abundant, indicating that numerous vesicles were caught in different phases of
      exocytosis or endocytosis. Freeze-fracture replicas made from quick-frozen or
      chemically fixed material showed a high number of vesicle openings (pits) in the
      presynaptic plasmalemma. No recovery occurred even after a prolonged period of
      rest, indicating that retrieval was impaired by zinc treatment. In conclusion,
      the present experimental paradigm created an unusual situation where fusion of
      synaptic vesicles to the plasma membrane could be activated independently from
      the release of transmitter.

PMID- 9153580
TI  - Properties of cloned rat alpha1A calcium channels transiently expressed in the
      COS-7 cell line.
AB  - The rat brain alpha1A calcium channel clone has been expressed in COS-7 cells
      together with the neuronal accessory subunits beta1b and alpha2-delta. From
      reverse transcriptase polymerase chain reaction (RT-PCR), immunocytochemistry and
      electrophysiology experiments, we have obtained no evidence that these cells
      contain any endogenous calcium channels. Transfected cells were identified by co
      expression of a cDNA for the reporter Green Fluorescent Protein. From
      immunocytochemical evidence, a high degree of co-expression was obtained between
      Green Fluorescent Protein and individual calcium channel subunits. When all three
      calcium channel subunits (alpha1, alpha2-delta and beta1b) were co-expressed,
      evidence was obtained that all subunits were present at the cell membrane.
      Voltage-dependent calcium currents were observed between 24 and 72 h after
      transfection with the three calcium channel subunits. The current density for the
      combination alpha1A/alpha2-delta/beta1b was 4.19 +/- 0.69 pA.pF(-1) and the
      current produced was slowly inactivating. The time constant of inactivation of
      the maximum I(Ba) was 332 +/- 46 ms (n = 5). The voltage-dependence of activation
      and steady-state inactivation had voltages of half activation and inactivation of
      9.5 +/- 2.5 mV and -30.4 +/- 1.5 mV respectively, and there was little overlap
      between the two curves. The alpha1A current was completely blocked by 100 microM
      Cd2+ and was also blocked by omega-conotoxin MVIIC (500 nM). Dose-inhibition
      curves and analysis of k(on) and k(off) for omega-agatoxin IVA both revealed
      apparent K(D) values of approximately 11 nM for alpha1A currents, with a k(on) of
      7.8 x 10(4) M(-1).s(-1). The results suggest that alpha1A expressed in these
      cells has some resemblance to the P type component of calcium current observed in
      native neurons, although it shows a somewhat greater degree of inactivation than
      native P current, more similar to the Q type current component. It also has an
      affinity for omega-agatoxin IVA 2-5 fold lower than reported for P current, but
      approximately 9-fold higher than reported for Q current.

PMID- 9153581
TI  - Importance of the different beta subunits in the membrane expression of the
      alpha1A and alpha2 calcium channel subunits: studies using a depolarization
      sensitive alpha1A antibody.
AB  - The plasma membrane expression of the rat brain calcium channel subunits alpha1A,
      alpha2-delta and the beta subunits beta1b, beta2a, beta3b and beta4 was examined
      by transient expression in COS-7 cells. Neither alpha1A nor alpha2-delta
      localized to the plasma membrane, either alone or when coexpressed. However,
      coexpression of alpha1A or alpha2-delta/alpha1A with any of the beta subunits
      caused alpha1A and alpha2 to be targetted to the plasma membrane. The alpha1A
      antibody is directed against an exofacial epitope at the mouth of the pore, which
      is not exposed unless cells are depolarized, both for native alpha1A channels in
      dorsal root ganglion neurons and for alpha1A expressed with a beta subunit. This
      subsidiary result provides evidence that either channel opening or inactivation
      causes a conformational change at the mouth of the pore of alpha1A.
      Immunostaining for alpha1A was obtained in depolarized non-permeabilized cells,
      indicating correct orientation in the membrane only when it was coexpressed with
      a beta subunit. In contrast, beta1b and beta2a were associated with the plasma
      membrane when expressed alone. However, this is not a prerequisite to target
      alpha1A to the membrane since beta3 and beta4 alone showed no differential
      localization, but did direct the translocation of alpha1A to the plasma membrane,
      suggesting a chaperone role for the beta subunits.

PMID- 9153582
TI  - Gradation of kainic acid-induced rat limbic seizures and expression of
      hippocampal heat shock protein-70.
AB  - Systemic injection of kainic acid (KA) induces limbic seizures in rats, which
      resemble human temporal lobe epilepsy, the most common form of adult human
      epilepsy. In this study, we have investigated KA-elicited limbic seizures in the
      rats by correlating the severity of the seizure attacks with the expression of
      hippocampal heat shock protein-70 (HSP70) which has been suggested to be a marker
      for neuronal injury/death in this model of seizures. After a systemic injection
      of KA, six stages of limbic seizures have been classified, namely, staring (stage
      1), wet dog shake (stage 2), hyperactivity (stage 3), rearing (stage 4), rearing
      and falling (stage 5), and jumping (stage 6). Stages 4, 5 and 6 were further
      divided into mild and severe sub-stages. HSP70 expression was not detected in
      animals with stages 1 and 2 seizures. At stage 3 a small amount of HSP70
      immunoreactive neurons was detected in the CA3 field and the dentate hilus. From
      stage 4 to stage 5 the degree of HSP70 immunoreactivity increased in the CA1
      field from a few positive cells in stage 4 mild to large numbers of
      immunoreactive neurons in stage 5 severe. HSP70 became detectable in pyramidal
      cells in the CA2 field from stage 5 severe and higher. In animals with stage 6
      seizures, the majority of HSP70 expression became located in glial cells
      throughout the whole hippocampus. We concluded that HSP70 expression in the
      hippocampus positively correlates with the severity of KA-elicited limbic
      seizures.

PMID- 9153583
TI  - Serpins inhibit the toxicity of amyloid peptides.
AB  - The amyloid plaque in Alzheimer's disease (AD) contains numerous proteins, some
      of which may be relevant to the pathogenesis of the disease. The serine protease
      inhibitor alpha1-antichymotrypsin is specifically localized in AD plaques. It is
      shown here that alpha1-antichymotrypsin and several other serine protease
      inhibitors (serpins) inhibit the toxicity of amyloid peptides on primary cortical
      nerve cell cultures as well as a clonal cell line. This inhibition of toxicity is
      not mediated via the serpin enzyme complex receptor, the transferrin receptor, or
      by interference with the polymerization of amyloid fibrils. Since a variety of
      synthetic serine protease inhibitors mimic the effects of serpins on amyloid
      toxicity, it is likely that the antiprotease activities of serpins are
      responsible for their biological effects.

PMID- 9153584
TI  - Cable properties of dendrites in hippocampal neurons of the rat mapped by a
      voltage-sensitive dye.
AB  - Dendrites of pyramidal neurons from embryonic rat hippocampus are investigated in
      culture using a voltage-sensitive fluorescent dye. The electrical response to
      somatic stimulation is observed as a time-resolved map with a resolution of 0.9
      microm at a time constant of 0.4 ms without signal averaging. The data are
      interpreted in terms of a tapering cable with Hodgkin-Huxley parametrization. The
      spread of short hyperpolarizing transients is damped by capacitive shunting. The
      invasion of an action potential is boosted by voltage-gated conductances of a low
      density. No irregularity is observed at a bifurcation. The passive cable
      parameters of internal resistance and membrane resistance at resting voltage are
      Ri = 300 omega cm and Rm = 40 (k)omega cm2 respectively, at a maximum sodium
      conductance of approximately 4.4 mS/cm2. The electrotonic length constant and the
      dynamic length constant at 1 kHz are 580 and 90 microm respectively. These
      results are compatible with electrophysiological data of dendrites in slices of
      adult hippocampus and with optical data of narrow processes of leech neurons in
      culture. The functional implications of boosting an action potential by voltage
      gated channels of low density are considered.

PMID- 9153585
TI  - Sequential role of hippocampus and amygdala, entorhinal cortex and parietal
      cortex in formation and retrieval of memory for inhibitory avoidance in rats.
AB  - The hippocampus and amygdala, the entorhinal cortex and the parietal cortex
      participate, in that sequence, both in the formation and in the expression of
      memory for a step-down inhibitory avoidance task in rats. Bilateral infusion of
      AP5 or muscimol caused retrograde amnesia when given 0 min after training into
      both hippocampus and amygdala, when given or 180 min after training into the
      entorhinal cortex, or when given 180 min after training into the parietal cortex.
      Therefore, memory formation requires the sequential and integrated activity of
      all these areas mediated by glutamate NMDA receptors in each case. Pre-test
      administration of CNQX 1 day after training into hippocampus and amygdala, 1 or
      31 days after training in entorhinal cortex, or 1, 31 or 60 days after training
      in the parietal cortex temporarily blocked retention test performance. Therefore,
      1 day after training, all these brain structures are necessary for retrieval; 1
      month later, the hippocampus and amygdala are no longer necessary for retrieval
      but the entorhinal and parietal cortex still are; and 60 days after training only
      the parietal cortex is needed. In all cases the mechanisms of retrieval require
      intact glutamate AMPA receptors.

PMID- 9153586
TI  - Evidence that spinal interneurons undergo programmed cell death postnatally in
      the rat.
AB  - Programmed cell death has been demonstrated in several specific neuronal
      populations as a mechanism for modulating the population size following
      differentiation, but its applicability to all neuronal types is unclear. Evidence
      for programmed cell death in some populations such as the numerous spinal
      interneurons has been lacking. We have studied the incidence of apoptosis in the
      rat spinal cord with three different methods and found a previously undocumented
      wave of apoptosis occurring in spinal grey matter shortly after birth. The
      apoptotic morphology was confirmed ultrastructurally. Dying cells were identified
      as neurons by immunocytochemical labelling for neuronal markers and had an
      anatomical distribution which indicated that most of the apoptotic cells were
      interneurons not motoneurons. This wave of apoptosis has the characteristics of a
      discrete developmental process and occurs later than that of either ventral horn
      motoneurons or dorsal root ganglion cells, to which most spinal interneurons are
      connected. These findings indicate that interneurons do undergo programmed cell
      death, and we suggest that this occurs in response to the earlier reduction in
      size of their main synaptic targets.

PMID- 9153588
TI  - Microinfusion of the metabotropic glutamate receptor agonist 1S,3R-1
      aminocyclopentane-1,3-dicarboxylic acid into the nucleus accumbens induces
      dopamine-dependent locomotor activation in the rat.
AB  - Although the striatum has one of the highest densities of metabotropic glutamate
      receptor (mGluR) binding sites in the brain, little is known about their
      physiological role. In this study we characterized the contribution of mGluRs
      located in the ventral part of the striatum (the nucleus accumbens) to the
      control of extrapyramidal motor function. Activation of mGluRs by local infusion
      of the selective agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R
      ACPD; 25, 50 and 100 nmol/0.5 microl) into the nucleus accumbens induced a dose
      dependent increase in locomotor activity in rats. Intra-accumbens infusion of a
      selective antagonist of mGluRs, alpha-methyl-4-carboxyphenylglycine (MCPG) did
      not modify spontaneous locomotion but decreased the locomotor response to 1S,3R
      ACPD. This effect appeared to be mediated by dopamine, since blockade of dopamine
      receptors with haloperidol (0.05 and 0.1 mg/kg i.p.) dose-dependently reduced
      1S,3R-ACPD-induced locomotor activation. Furthermore, D-amphetamine (0.5 mg/kg,
      i.p.) combined with intra-accumbens infusion of 1S,3R-ACPD (100 nmol) potentiated
      the locomotor hyperactivity response to a higher level than that seen with a
      single treatment with either drug. In contrast, D-amphetamine-induced
      hypermotility was abolished by infusion of MCPG (100 nmol) into the nucleus
      accumbens. These results demonstrate that glutamate may control extrapyramidal
      motor function through metabotropic receptors. Furthermore, activation of
      metabotropic glutamate receptors appears to act in synergy with the dopamine
      system at the level of the nucleus accumbens to produce a motor stimulant
      response.

PMID- 9153587
TI  - Spontaneous and repetitive calcium transients in C2C12 mouse myotubes during in
      vitro myogenesis.
AB  - Fluorescence videomicroscopy was used to monitor changes in the cytosolic free
      Ca2+ concentration ([Ca2+]i) in the mouse muscle cell line C2Cl2 during in vitro
      myogenesis. Three different patterns of changes in [Ca2+]i were observed: (i)
      [Ca2+]i oscillations; (ii) faster Ca2+ events confined to subcellular regions
      (localized [Ca2+]i spikes) and (iii) [Ca2+]i spikes detectable in the entire
      myotube (global [Ca2+]i spikes). [Ca2+]i oscillations and localized [Ca2+]i
      spikes were detectable following the appearance of caffeine-sensitivity in
      differentiating C2Cl2 cells. Global [Ca2+]i spikes appeared later in the process
      of myogenesis in cells exhibiting coupling between voltage-operated Ca2+ channels
      and ryanodine receptors. In contrast to [Ca2+]i oscillations and localized
      [Ca2+]i spikes, the global events immediately stopped when cells were perfused
      either with a Ca2+-free solution, or a solution with TTX, TEA and verapamil. To
      explore further the mechanism of the global [Ca2+]i spikes, membrane currents and
      fluorescence signals were measured simultaneously. These experiments revealed
      that global [Ca2+]i spikes were correlated with an inward current. Moreover,
      while the depletion of the Ca2+ stores blocked [Ca2+]i oscillations and localized
      [Ca2+]i spikes, it only reduced the amplitude of global [Ca2+]i spikes. It is
      suggested that, during the earlier stages of the myogenesis, spontaneous and
      repetitive [Ca2+]i changes may be based on cytosolic oscillatory mechanisms. The
      coupling between voltage-operated Ca2+ channels and ryanodine receptors seems to
      be the prerequisite for the appearance of global [Ca2+]i spikes triggered by a
      membrane oscillatory mechanism, which characterizes the later phases of the
      myogenic process.

PMID- 9153589
TI  - Multiple types of Ca2+ channels in mouse motor nerve terminals.
AB  - We measured neurotransmitter release and motor nerve terminal currents in mouse
      phrenic nerve-diaphragm and triangularis sterni preparations, to evaluate the
      role of Ca2+-channel subtypes in regulating transmitter release. Saturated
      concentrations of either omega-agatoxin IVA [omega-Aga-IVA (0.3 microM), a
      blocker of P-type Ca2+ channels] or omega-conotoxin MVIIC [omega-CTx-MVIIC (2
      microM), a P- and Q-type Ca2+-channel blocker], inhibited nerve-evoked muscle
      contractions and the amplitude of endplate potentials respectively. In contrast,
      combined treatment with nifedipine (50 microM, a blocker of L-type Ca2+ channels)
      plus omega-conotoxin GVIA [omega-CTx-GVIA (2 microM), a blocker of N-type Ca2+
      channels] did not elicit inhibitory effects on nerve-evoked muscle contractions,
      endplate potentials or nerve terminal waveforms. Because of the non-linear
      relationship between endplate potentials and Ca2+ signals, a small decrease in
      presynaptic Ca2+ entry can significantly reduce the amplitude of the endplate
      potential. Thus, we applied 3,4-diaminopyridine (3,4-DAP, a K+-channel blocker)
      or high Ca2+ (10 mM) to accelerate and amplify the endplate potentials and Ca2+
      currents. The endplate potentials amplified by 3,4-DAP or by high Ca2+
      correspondingly proved to be quite resistant to both omega-Aga-IVA and omgea-CTx
      MVIIC; omega-Aga-IVA exerted only a partial inhibitory effect on endplate
      potentials, and the omega-Aga-IVA-resistant component was further inhibited by
      omega-CTx-MVIIC. The component that was resistant to the two toxins could be
      completely blocked by the non-selective Ca2+ channel blocker Cd2+ (300 microM). A
      combination of the two toxins had no significant effects on either spontaneous
      transmitter release or postsynaptic resting membrane potentials of the diaphragm
      preparation and the Na+ and K+ waveforms of the triangularis sterni preparations.
      This finding suggests a preferential inhibitory effect at a presynaptic site.
      Measuring the Ca2+ currents in the triangularis sterni also revealed partial
      inhibition by omega-CTx-MVIIC with further incomplete inhibition by omega-Aga
      IVA. Cd2+ (300 microM) abolished the toxin-resistant component of the Ca2+
      current. In contrast, a combination of nifedipine (50 microM) with omega-CTx-GVIA
      (2 microM) was without inhibitory effect. We conclude that multiple types of Ca2+
      channels, i.e. omega-Aga-IVA-sensitive, omega-CTx-MVIIC-sensitive and toxin
      resistant Ca2+ channels, coexist in mouse motor nerve terminals.

PMID- 9153590
TI  - Development of G protein-mediated Ca2+ channel regulation in mouse embryonic stem
      cell-derived neurons.
AB  - Besides other mechanisms, the influx of Ca2+ into embryonic neurons controls
      growth and differentiation processes. To study the expression and regulation of
      voltage-gated Ca2+ channels during early neurogenesis, we measured whole-cell
      Ca2+ currents (I(Ca)) in neurons developing from pluripotent embryonic stem
      cells. Various receptor agonists, including somatostatin and baclofen, reversibly
      inhibited I(Ca) in embryonic stem cell-derived neurons. The effects of
      somatostatin and baclofen were abolished by pretreatment of cells with pertussis
      toxin and mimicked by intracellular infusion of guanosine 5'-O-(3
      thiotriphosphate), suggesting the involvement of pertussis toxin-sensitive G
      proteins in I(Ca) inhibition. Investigations at different stages of neuronal
      differentiation showed that somatostatin efficiently suppressed L- and N-type
      Ca2+ channels in immature as well as mature neurons. In contrast, inhibition of L
      and N-type channels by baclofen was rarely observed at the early stage. In
      terminally differentiated neurons, responses to baclofen were as prominent as
      those to somatostatin but were confined to N-type Ca2+ channels. The stage
      dependent sensitivity of voltage-gated Ca2+ channels to somatostatin and baclofen
      was not due to differential expression of G alpha(o) isoforms, as revealed by
      reverse transcription-polymerase chain reaction and immunofluorescence
      microscopy. These findings demonstrate that specific neurotransmitters such as
      somatostatin regulate voltage-gated Ca2+ channels via G proteins during the early
      stages of neurogenesis, thus providing a mechanism for the epigenetic control of
      neuronal differentiation.

PMID- 9153591
TI  - Effects of noradrenaline on frequency tuning of rat auditory cortex neurons.
AB  - The selectivity of rat auditory cortex neurons for pure tone frequency was
      studied during and after ionophoretic application (5-40 nA) of noradrenaline in
      urethane-anaesthetized rats. The dominant effect induced by noradrenaline was a
      significant decrease in spontaneous (93/268 cells) and evoked activity (133/268
      cells) which outlasted the application. In the whole population of cells (n =
      268) the signal-to-noise ratio, computed using as the signal either the mean
      evoked response or the response at the best frequency, was unchanged during
      noradrenaline application. It was significantly increased only for cells showing
      significantly decreased spontaneous activity, and was significantly decreased for
      cells showing increased spontaneous activity. Frequency selectivity was
      significantly increased for the whole population during and after noradrenaline
      application. It was also significantly increased for cells showing significantly
      decreased evoked activity, and was significantly decreased for cells showing
      increased evoked activity. The noradrenaline-induced inhibition was not blocked
      by propranolol (beta antagonist); it was blocked by prazosin (alpha1 antagonist)
      and partly mimicked by phenylephrine (alpha1 agonist). GABA, which also inhibited
      spontaneous and evoked activity, slightly increased the signal-to-noise ratio and
      significant increased frequency selectivity. However, when noradrenaline was
      ejected in the presence of bicuculline at doses that were able to block GABAergic
      inhibition, the inhibitory effects of noradrenaline on spontaneous and evoked
      activity were still observed. The possible function of noradrenaline-induced
      inhibitions in sensory cortices is briefly discussed.

PMID- 9153592
TI  - Susceptibility of cerebellar granule neurons derived from Bcl-2-deficient and
      transgenic mice to cell death.
AB  - Overproduced Bcl-2 oncoprotein has been shown to suppress cell death induced by a
      variety of stimuli in many cell types, including neuronal cells. Because bcl-2 is
      expressed in the nervous system where massive cell death is observed during
      development, endogenous Bcl-2 is likely to be involved in regulating neuronal
      cell death. Here we examined the possible role of endogenous Bcl-2 in the
      regulation of neuronal cell survival in the central nervous system using primary
      cultured cerebellar granule neurons from bcl-2-deficient, wild-type and NSE-bcl-2
      transgenic mice. Cerebellar granule neurons from bcl-2-deficient mice were more
      susceptible than those from normal littermates to death induced by reducing the
      K+ concentration of the medium from high (25 mM) to low (5 mM), and neurons from
      bcl-2-transgenic mice were least susceptible. Similar results were obtained when
      cell death was induced by serum withdrawal under high K+ conditions or by the
      presence of etoposide, A23187 or nimodipine. Consistently, bcl-2 deficiency
      reduced the number of cerebellar granule neurons per mouse. These results
      indicate that Bcl-2 impedes neuronal cell death induced by various stimuli in a
      dose-dependent manner, and that endogenous levels of Bcl-2 are able to regulate
      neuronal cell survival in the central nervous system.

PMID- 9153593
TI  - Expression of GABA(A) receptor subunit mRNAs by layer V pyramidal cells of the
      rat primary visual cortex.
AB  - The expression of the GABA(A) receptor subunit mRNAs by layer V pyramidal neurons
      of the primary visual cortex and cerebellar Purkinje cells was analysed by single
      cell reverse transcription of the mRNAs and amplification of the resulting cDNAs
      by the polymerase chain reaction. Neurons were identified by infrared
      videomicroscopy, and GABA(A)-mediated miniature inhibitory postsynaptic currents
      were recorded. In Purkinje cells, alpha1, beta2, beta3, gamma2S and gamma2L
      subunit mRNAs were detected within a single cell. In layer V pyramidal cells, a
      total of ten GABA(A) receptor subunit mRNAs could be detected, with a mean of
      seven subunit mRNAs per cell, suggesting GABA(A) receptor heterogeneity within a
      single pyramidal cell.

PMID- 9153594
TI  - Fluorescent dye prelabelled microglial cells migrate into organotypic hippocampal
      slice cultures and ramify.
AB  - Microglial cells with their characteristic ramified morphology are exclusively
      found in healthy CNS tissue, whereas various pathologies are associated with the
      occurrence of amoeboid, macrophage-like cells. It is still a matter of discussion
      whether amoeboid cells are blood-derived macrophages, or whether a characteristic
      change in morphology, reflecting activation of previously ramified microglia,
      takes place. Cells in dissociated microglia culture obtained from healthy rat
      brains, inevitably developing this amoeboid morphology, were labelled with a
      fluorescent dye and transferred onto organotypic hippocampal slice cultures.
      Prelabelled cells with amoeboid morphology invaded these slice cultures and had,
      after 9 days in vitro, gradually transformed into highly ramified cells. Our
      findings strengthen the hypothesis that the observed amoeboid and ramified cells
      belong to a single population of microglia, appearing with different morphologies
      depending on the presence of stimuli provided by the CNS microenvironment.
      Microglial cells obviously appear in different shapes and can switch from
      immunologically resting to activated modes and vice versa.

PMID- 9153595
TI  - Different routes of Ca2+ influx in NMDA-mediated generation of nitric oxide and
      arachidonic acid.
AB  - Nitric oxide and arachidonic acid act as inter- and intracellular messengers in
      the central nervous system. It is well known that the NMDA-mediated generation of
      nitric oxide and arachidonic acid is dependent on extracellular Ca2+. However,
      the role of voltage-dependent calcium channels (VDCCs) in this regard is poorly
      understood. We report here that NMDA-mediated nitric oxide production in striatal
      neuron cultures is blocked (80%) by the L-type VDCC antagonist nifedipine, but
      not by omega-conotoxin or omega-agatoxin IVA, antagonists of the N- and P-type
      VDCCs respectively. By contrast, none of the VDCC antagonists inhibited the NMDA
      mediated release of arachidonic acid. These data indicate that permeation through
      different Ca2+ channels is responsible for the production of arachidonic acid and
      nitric oxide in striatal neurons.

PMID- 9153596
TI  - Disorders of semantic memory.

PMID- 9153597
TI  - Neurological stamp: Wilhelm Griesinger (1817-68).

PMID- 9153599
TI  - Epidemiological features of Guillain-Barre syndrome in Sweden, 1978-93.
AB  - OBJECTIVES: To describe the incidence of Guillain-Barre syndrome in Sweden during
      the period 1978-93 and its temporal and geographical variations. METHODS:
      Stratified and Poisson regression analyses and tests for detection of small
      epidemics were applied to population based hospital discharge data from 2257
      incident cases of Guillain-Barre syndrome in Sweden during the study period.
      RESULTS: The incidence of Guillain-Barre syndrome was (1) 1.77 per 100000 person
      years when age adjusted to the European population; (2) higher in males; and (3)
      stable across time, although occasional increases of annual incidence rates were
      found-namely, in 1978 (relative risk (RR) 1.30 (95% CI 1.10-1.54)), and in 1983
      (RR 1.24 (95% CI 1.06-1.40)). The incidence increased with age and was bimodal,
      with peaks at 20-24 and 70-74 years. There was a moderate but significant
      seasonality with a peak in August, particularly among the young age groups. The
      age adjusted incidence by county varied from 1.11 to 2.57 per 100000 person
      years. Neither temporal nor spatial clustering was significant, except during the
      period July-September in 1983 at ages below 40 years. CONCLUSIONS: The incidence
      of Guillain-Barre syndrome in Sweden during the period 1978-93 had a magnitude
      similar to those described in other surveys, a bimodal distribution by age, and
      modest geographical and temporal variations with significantly high rates in 1978
      and 1983 and in autumn. Minor outbreaks might have passed unnoticed up to the
      present. Whereas reported drug induced cases of Guillain-Barre syndrome may in
      part explain the high incidence in 1983, the cause of the aberrant incidence in
      1978 remains unknown. Epidemiological surveillance of Guillain-Barre syndrome in
      Sweden might have been useful.

PMID- 9153598
TI  - Olfactory dysfunction in Parkinson's disease.
AB  - OBJECTIVE: To evaluate olfactory function in Parkinson's disease. METHODS: A
      standardised odour identification test was used, together with an evoked
      potential assessment with hydrogen sulphide. In addition, histological analysis
      was performed on the olfactory bulbs of cadavers who died from Parkinson's
      disease. RESULTS: Over 70% of patients studied (71 of 96) were outside the 95%
      limit of normal on the identification test in an age matched sample and there was
      an unusual pattern of selective loss to certain odours, not hitherto described.
      The evoked potentials were significantly delayed but of comparable amplitude to a
      control matched population. Of the 73 patients studied only 37 had a technically
      satisfactory record containing a clear response to both gases and of these, 12
      were delayed. For H2S there was more delay on stimulating the right nostril than
      the left. Some patients with normal smell identification test scores had delayed
      evoked potentials. In the pathological examination of olfactory bulbs from eight
      brains, changes characteristic of Parkinson's disease (Lewy bodies) were seen in
      every olfactory bulb, particularly in the anterior olfactory nucleus, and were
      sufficiently distinct to allow a presumptive diagnosis of Parkinson's disease.
      CONCLUSIONS: Olfactory damage in Parkinson's disease is consistent and severe and
      may provide an important clue to the aetiology of the disease.

PMID- 9153600
TI  - A Japanese family with a variant of Gerstmann-Straussler-Scheinker disease.
AB  - OBJECTIVE: A new variant of Gerstmann-Straussler-Scheinker disease (GSS) was
      reported, which had a substitution of glutamate to lysine at codon 219 (E219K) in
      addition to a P102L mutation on the same allele of the PrP gene. However,
      clinical features were not detailed and pathological studies were not done.
      Unusual clinical, neuroradiological, and pathological findings are reported for
      these patients. METHODS AND RESULTS: Clinical presentations of the patients in
      the same family were variable; progressive dementia with minimal ataxia in some
      patients but ataxia without dementia in others. PET studies with 18F-2-fluoro-2
      deoxyglucose (FDG) disclosed a relative decrease of FDG uptake in bilateral
      temporoparietal cortices of a patient with dementia, but in the cerebellar
      cortices in a patient with ataxia. At necropsy, a patient with dementia had
      multicentric and diffuse plaques stained with PrP antiserum, but not with
      haematoxylin and eosin or Congo red, in the cerebral and cerebellar cortices.
      CONCLUSION: Neurological and neuropathological features in the patients were
      atypical of the classic form of GSS with P102L mutation. The absence of Congo red
      staining prion protein plaques is probably attributable to E219K polymorphism on
      the same allele of the PrP gene.

PMID- 9153601
TI  - Psychiatric profiles and patterns of cerebral blood flow in focal epilepsy:
      interactions between depression, obsessionality, and perfusion related to the
      laterality of the epilepsy.
AB  - OBJECTIVES: In a study of patients with focal epilepsy the hypothesis was
      explored that different measurements of psychopathology are related to specific
      distributions of cerebral perfusion. METHODS: Forty patients had SPECT performed
      with (99m)Tc-HMPAO. In addition, patients received a psychiatric evaluation with
      the following psychiatric questionnaires: the Beck depression inventory, the
      Leyton obsessionality inventory, the Bear-Fedio questionnaire, and the social
      stress and support interview. Patients were analysed in two groups according to
      the laterality of the epilepsy. Nine patients were excluded based on poor quality
      scans (n = 1), unlateralised epilepsy (n = 4), and left or ambidextrous
      handedness (n = 4). RESULTS: There were no overall differences between the left
      and right epilepsy groups on measures of psychopathology. Associations were found
      between scores on some of the rating scales and regional cerebral blood flow.
      Specifically, for patients with left sided epilepsy, higher scores on the Beck
      depression inventory were associated with lower contralateral temporal and
      bilateral frontal perfusion, and higher occipital perfusion. For patients with
      right sided epilepsy higher scores on the Leyton obsessionality inventory were
      associated with increased perfusion in ipsilateral temporal, thalamic, and basal
      ganglia regions and bilateral frontal regions. CONCLUSION: The results do not
      support the notion that lateralised epileptogenic lesions are associated with
      different levels of depression, obsessionality, or personality traits. They
      support the view that certain psychopathological symptom patterns are related to
      specific regional dysfunctions depending on the laterality of a hemispheric
      lesion.

PMID- 9153602
TI  - Relation between cognitive dysfunction and pseudobulbar palsy in amyotrophic
      lateral sclerosis.
AB  - OBJECTIVES: To examine the relation between cognitive dysfunction and
      pseudobulbar features in patients with amyotrophic lateral sclerosis (ALS).
      METHODS: The performance of two patient groups, ALS with pseudobulbar palsy (n =
      24) and ALS without pseudobulbar palsy (n = 28), was compared with 28 healthy age
      matched controls on an extensive neuropsychological battery. Tests used were the
      national adult reading test, short form of the WAIS-R, recognition memory test,
      Kendrick object learning test, paired associate learning, Wisconsin card sorting
      test, verbal fluency, Stroop and negative priming tests, a random movement
      joystick test, and a computerised Tower of Hanoi test. RESULTS: Tests of
      executive function showed a pronounced deficit on written verbal fluency in both
      ALS groups in comparison to controls, which tended to be more prominent in
      patients with ALS with pseudobulbar palsy. The random movement joystick test (a
      non-verbal test of intrinsic movement generation) showed an impairment in the
      generation of random sequences in patients with pseudobulbar palsy only. The
      computerised Tower of Hanoi showed a subtle planning impairment (shorter planning
      times) in all the patients with ALS compared with controls on trials requiring
      more complex solutions. In addition the pseudobulbar patients displayed shorter
      planning times on complex trials, and tended to solve these trials less
      accurately. There was also evidence of a deficit for all patients with ALS in
      comparison with controls on total errors and number of categories achieved on the
      Wisconsin card sorting test and a strong tendency towards an impairment on a task
      of selective attention and cognitive inhibition (negative priming). A word
      recognition memory deficit was showed across both ALS groups. CONCLUSIONS: This
      study elicited cognitive deficits (involving predominantly executive processes,
      with some evidence of memory impairment) in patients with ALS and further
      strengthened the link between ALS and frontal lobe dysfunction, this being more
      prominent in patients with pseudobulbar palsy. However, cognitive impairments
      suggestive of extramotor cortical involvement were not exclusive to this
      subgroup.

PMID- 9153603
TI  - Assessment of autonomic dysreflexia in patients with spinal cord injury.
AB  - OBJECTIVES AND METHODS: To assess the impairment of supraspinal control over
      spinal sympathetic centres and the occurrence of autonomic dysreflexia in
      patients with spinal cord injury. Autonomic dysreflexia is caused by the
      disconnection of spinal sympathetic centres from supraspinal control and is
      characterised by paroxysmal hypertensive episodes caused by non-specific stimuli
      below the level of the lesion. Therefore, patients with spinal cord injury were
      examined clinically and by different techniques to assess the occurrence of
      autonomic dysreflexia and to relate disturbances of the sympathetic nervous
      system to episodes of autonomic dysreflexia. RESULTS: None of the paraplegic
      patients, but 59% (13/22) of tetraplegic patients (91% of the complete, 27% of
      the incomplete patients) presented signs of autonomic dysreflexia during
      urodynamic examination. Only 62% of the tetraplegic patients complained about
      symptoms of autonomic dysreflexia. Pathological sympathetic skin responses (SSRs)
      of the hands were related to signs of autonomic dysreflexia in 93% of cases. No
      patient with preserved SSR potentials of the hands and feet showed signs of
      autonomic dysreflexia, either clinically or during urodynamic examination.
      Ambulatory blood pressure measurements (ABPMs) indicated a loss of circadian
      blood pressure rhythm (sympathetic control) but preserved heart rate rhythm
      (parasympathetic regulation) only in patients with complete tetraplegia.
      Pathological ABPM recordings were seen in 70% of patients with symptoms of
      autonomic dysreflexia. CONCLUSIONS: The urodynamic examination was more sensitive
      in indicating signs of autonomic dysreflexia in patients with spinal cord injury,
      whereas SSR allowed the assessment of the degree of disconnection of the
      sympathetic spinal centres from supraspinal control. Using ABPM recordings the
      occurrence of episodes of autonomic dysreflexia over 24 hours and the
      effectiveness of therapeutical treatment can be assessed.

PMID- 9153604
TI  - Does routine follow up after head injury help? A randomised controlled trial.
AB  - OBJECTIVE: To evaluate the Medical Disability Society's 1988 recommendation that
      "every patient attending hospital after a head injury should be registered and
      offered an outpatient follow up appointment" by determining whether offering a
      routine follow up service to patients presenting to hospital with a head injury
      of any severity affects outcome six months later. DESIGN: A randomised controlled
      trial design with masked assessment of outcome. SETTING: A mixed rural and urban
      health district with a population of about 560000. PATIENTS: 1156 consecutive
      patients resident in Oxfordshire aged between 16 and 65 years presenting over 13
      months to accident and emergency departments or admitted to hospital and
      diagnosed as having a head injury of any severity, including those with other
      injuries. INTERVENTIONS: Patients were registered and randomised to one of two
      groups. Both groups continued to receive the standard service offered by the
      hospitals. The early follow up group were approached at 7-10 days after injury
      and offered additional information, advice, support, and further intervention as
      needed. All randomised patients were approached for follow up assessment six
      months after injury by independent clinicians blind to their group. MAIN OUTCOME
      MEASURES: Validated questionnaires were used to elicit ratings of post-concussion
      symptoms (the Rivermead postconcussion symptoms questionnaire), and changes in
      work, relationships, leisure, social, and domestic activities (the Rivermead head
      injury follow up questionnaire). RESULTS: The two groups were comparable at
      randomisation. Data was obtained at six months on 226 of 577 "control" patients
      and 252 of 579 "trial" patients (59% were lost to follow up). There were no
      significant differences overall between the trial and control groups at follow
      up, but subgroup analysis of the patients with moderate or severe head injuries
      (posttraumatic amnesia > or = one hour, or admitted to hospital), showed that
      those in the early intervention group had significantly fewer difficulties with
      everyday activities (P = 0.03). CONCLUSIONS: The results from the 41% of patients
      followed up do not support the recommendation of offering a routine follow up to
      all patients with head injury, but they do suggest that routine follow up is most
      likely to be beneficial to patients with moderate or severe head injuries. Some
      of those with less severe injuries do continue to experience difficulties and
      need access to services. A further trial is under way to test these conclusions.

PMID- 9153605
TI  - Robert Whytt and the stretch reflex.

PMID- 9153606
TI  - Preoperative risk assessment for carotid occlusion by transcranial Doppler
      ultrasound.
AB  - OBJECTIVES: An endovascular carotid balloon occlusion test with continuous
      intracranial monitoring by transcranial Doppler sonography was performed in 55
      patients for prediction of tolerance of a required permanent occlusion of the
      carotid artery. METHODS: Blood flow velocities of the ipsilateral middle cerebral
      artery during occlusion were recorded and compared with clinical tolerance during
      an occlusion test as well as with postoperative outcome after an eventual
      permanent occlusion. To stress the capacity of the cerebral circulation to
      tolerate the occlusion acetazolamide was injected before occlusion in all
      patients. RESULTS: The onset of neurological symptoms during temporary occlusion
      was dependent on the percentage fall of mean blood flow velocity relative to
      baseline rather than on absolute flow velocities during the time of occlusion.
      Patients with a fall of mean flow velocity of less than 30% tolerated temporary
      and permanent occlusion, with the exception of two patients who developed an
      infarction due to thromboembolism after iatrogenic sacrifice of the carotid
      artery. Patients with a major decrease developed neurological symptoms during
      occlusion in 55% and, in cases of carotid ligation, a haemodynamic infarction
      occurred. CONCLUSION: The results show that transcranial Doppler monitoring as a
      part of an endovascular balloon occlusion test may be a reliable technique for
      preoperative risk assessment for permanent occlusion of the carotid artery.

PMID- 9153607
TI  - The efficacy of subcutaneous sumatriptan in the treatment of recurrence of
      migraine headache.
AB  - OBJECTIVES: To investigate the efficacy of a second subcutaneous dose of 6 mg
      sumatriptan in the treatment of recurrence of headache after successful treatment
      of a migraine attack with an initial 6 mg dose. METHODS: In a prospective,
      randomised, placebo controlled, double blind, parallel group study, 803 patients
      were treated for one to three migraine attacks with severe or moderate headache
      with a subcutaneous injection of 6 mg sumatriptan. Any subsequent recurrence of
      migraine headache was treated with a randomised second injection of sumatriptan
      or placebo. Recurrence was defined as a headache of moderate or severe intensity
      occurring 1-24 hours after the initial dose in a patient whose headache had been
      relieved by sumatriptan (reduction of headache severity from severe or moderate
      to mild or none after one hour). RESULTS: Headache recurrence was reported by 10%
      15% of patients. At each attack, 6 mg sumatriptan given subcutaneously was
      significantly (P < 0.0005) more effective than placebo at relieving recurrent
      headache after one hour (84%-93% v 31%-50% of patients); 76%-83% of patients
      reported headache relief one hour after the initial dose of sumatriptan.
      Sumatriptan was generally well tolerated. CONCLUSIONS: Up to 15% of patients with
      migraine experience significant recurrence of headache after successful treatment
      with subcutaneous sumatriptan, and this recurrence is effectively treated by a
      further dose of subcutaneous sumatriptan.

PMID- 9153608
TI  - Octave Landry's ascending paralysis and the Landry-Guillain-Barre-Strohl
      syndrome.

PMID- 9153609
TI  - The role of weakness of triceps surae muscles in astasia without abasia.
AB  - OBJECTIVE: To investigate the role of weakness of the bilateral triceps surae
      muscles-the gastrocnemius and soleus muscles-in astasia without abasia and
      whether compensating for muscle weakness with ankle-foot orthoses improves this
      disability. DESIGN: Case-control study of clinical findings and before and after
      trial of ankle-foot orthoses. SETTING: Clinics of the departments of
      rehabilitation medicine of two university hospitals. PATIENTS: A stilts group
      consisting of 23 patients with astasia without abasia, and a non-stilts group
      without this phenomenon consisting of 12 patients with hereditary motor sensory
      neuropathy, 15 patients with lumbosacral spondylotic radiculopathy or
      spondylolisthesis, and 20 healthy volunteers. MAIN OUTCOME MEASURE: Clinical
      findings of the stilts and non-stilts groups were compared and the sensitivity
      and specificity of each clinical finding was calculated. The length of the centre
      of foot pressure (COP) while standing was measured in a bilateral below knee
      amputee and 16 consecutive patients in the stilts group with and without ankle
      foot orthoses. RESULTS: Weakness of the triceps surae muscles was the only
      finding that differed significantly between the two groups and was both sensitive
      and specific. The amputee was unable to stand in place without dorsiflexion
      bumpers, which functioned similarly to the triceps surae muscle. Bilateral ankle
      foot orthoses improved the COPs of 14 out of 16 patients. CONCLUSION: The main
      cause of astasia without abasia is weakness of the triceps surae muscles, and
      this disability is improved by bilateral ankle-foot orthoses.

PMID- 9153610
TI  - Cerebellar atrophy and prognosis after temporal lobe resection.
AB  - OBJECTIVE: Experimental data indicate inhibitory effects of the cerebellum on
      seizure activity. Structural damage such as cerebellar atrophy, which is a common
      finding in patients with chronic epilepsy, may reduce these effects. METHODS:
      Outcome after temporal lobectomy was studied in 78 consecutive patients, with or
      without cerebellar atrophy diagnosed by MRI. RESULTS: Thirty five patients (45%)
      showed cerebellar atrophy. At a mean follow up of 14.6 (range, 6-40) months, 50
      patients (64%) had no postoperative seizures. In these patients, the frequency of
      cerebellar atrophy was significantly lower (34%) than in patients who relapsed
      (64%, p < 0.01). Occurrence of generalised tonic-clonic seizures (GTCS) within
      two years before surgery, occurrence of GTCS at any time preoperatively, long
      duration of epilepsy, and older age at surgery were also associated with
      recurrence of seizures. Multiple logistic regression analysis suggested
      occurrence of GTCS within two years before surgery and cerebellar atrophy as the
      main predictive indicators. When both factors were present, the percentage of
      patients remaining seizure free since surgery fell to 30%, compared with 60% when
      only GTCS were present, 78.6% when only cerebellar atrophy was present, and 87.5%
      when both factors were absent. CONCLUSIONS: Cerebellar atrophy shown by MRI was a
      frequent finding in surgically treated patients with temporal lobe epilepsy. The
      presence of cerebellar atrophy seems to worsen the prognosis after temporal lobe
      resection.

PMID- 9153611
TI  - Urodynamic and neurophysiological evaluation in Parkinson's disease and multiple
      system atrophy.
AB  - AIMS: To determine whether Parkinson's disease and multiple system atrophy each
      has a distinct pattern of micturition abnormalities and whether a urodynamic
      evaluation could be useful in the differential diagnosis between the two
      diseases. METHODS: Sixty two patients (30 with Parkinson's disease and 32 with
      multiple system atrophy) underwent a complete urodynamic evaluation and
      neurophysiological testing. RESULTS: Of the parkinsonian patients 36.6% had
      normal micturition findings with normal bladder sensitivity; 26.7% had delayed or
      incomplete pelvic floor relaxation; 26.7% had hyperreflexia with
      vesicosphincteric synergy; and 10% had hyperreflexia with vesicosphincteric
      synergy associated with incomplete pelvic floor relaxation. Parkinsonian patients
      with a normal urodynamic pattern had significantly less severe disease and a
      shorter duration of disease in years than those who had abnormal patterns.
      Patients with hyperreflexia had significantly higher severity of disease. All the
      patients with multiple system atrophy had hyperreflexia with synergy. Two
      urodynamic patterns were identified: hyperreflexia with vesicosphincteric synergy
      (90.6% of patients), and hyperreflexia with vesicosphincteric synergy and
      incomplete pelvic floor relaxation (in 9.4%). Hyperreflexia with synergy
      correlated neither with the severity nor with the duration of disease. Sphincter
      EMG analysis showed that all the parkinsonian patients had normal sphincter EMG
      whereas 24 of the 32 patients with multiple system atrophy had neurogenic signs.
      CONCLUSIONS: Urodynamic evaluation and sphincter EMG are both useful tests in the
      differential diagnosis between Parkinson's disease and multiple system atrophy.
      Urodynamic findings may be abnormal before patients with multiple system atrophy
      reach an advanced stage of the disease. Recordings of EMGs from perineal muscles
      become abnormal as the disease progresses in multiple system atrophy but not in
      Parkinson's disease.

PMID- 9153612
TI  - Impact on clinical outcome of secondary brain insults during the neurointensive
      care of patients with subarachnoid haemorrhage: a pilot study.
AB  - OBJECTIVE: To analyse the occurrence and influence on outcome of secondary brain
      insults during neurointensive care of patients with subarachnoid haemorrhage.
      METHODS: Sixty one seriously ill patients with subarachnoid haemorrhage with a
      poor neurological grade, acute hydrocephalus, or intraventricular and/or
      intracerebral haemorrhages, who were referred as emergency cases to the
      neurosurgical intensive care unit during 1990 and 1991, comprised the study
      patients. RESULTS: The follow up performed according to the Glasgow outcome scale
      14 months (median) later showed 23 patients with good recovery (38%), 11 with
      moderate disability (18%), seven with severe disability (11%), and two in a
      vegetative state (3%); 18 patients had died (30%). Clinical outcome was
      significantly related to the CT modified Hunt and Hess grade (P = 0.006). In
      total, 164 secondary brain insults (potentially avoidable factors) of various
      types were seen at the unit during the first seven days after the haemorrhage.
      Patients with a favourable outcome had significantly fewer secondary insults than
      patients with an unfavourable outcome (P = 0.0008). The occurrence of insults in
      each patient was related to the neurological grade (CT modified Hunt and Hess
      grade, P = 0.05). Multivariate analysis with the CT modified Hunt and Hess grade
      and the number of secondary brain insults during the first week as explanatory
      variables and favourable outcome as the dependent variable, showed that the
      number of complications was a significant independent predictor of favourable
      outcome (beta = -0.38, SE(beta) = 0.17, P = 0.03), whereas the CT modified Hunt
      and Hess grade did not reach significance (beta = -1.2, SE(beta) = 0.81, P =
      0.14). CONCLUSIONS: The clinical outcome after subarachnoid haemorrhage is at
      least partly determined by the number of secondary insults. Therefore, vigorous
      attempts should be made to avoid all events that may potentially increase the
      risk of secondary cerebral ischaemia. Prospective studies must be initiated to
      define the role of "priming" of the brain and the impact of specific individual
      secondary insults in patients with subarachnoid haemorrhage.

PMID- 9153613
TI  - Motor evoked potentials in the preoperative and postoperative assessment of
      normal pressure hydrocephalus.
AB  - Motor evoked potentials and central motor conduction time (CMCT) were examined
      from both upper and lower limbs in patients with normal pressure hydrocephalus to
      find a predictor for the success of shunting procedures. The hypotheses that
      walking disturbances are due to pyramidal tract compression as well as the
      possibility that the upper limbs are affected subclinically in these patients
      were also studied. The study suggests that the walking disturbances are not the
      result of a major pyramidal tract dysfunction but probably involve the
      sensorimotor integration leading to normal gait. Furthermore, CMCT measured with
      electromagnetic motor stimulation can help in selecting the patients that will
      benefit from shunting. The study does not provide electrophysiological evidence
      of upper limb involvement in normal pressure hydrocephalus.

PMID- 9153614
TI  - Sound movement detection deficit due to a brainstem lesion.
AB  - Auditory psychophysical testing was carried out on a patient with a central
      pontine lesion involving the trapezoid body, who presented with a deficit in
      sound localisation and sound movement detection. A deficit in the analysis of
      time and intensity differences between the ears was found, which would explain
      the deficit in detection of sound movement. The impaired detection of sound
      movement, due to a lesion interfering with convergence of auditory information at
      the superior olive, suggests this structure to be critical for human sound
      movement analysis.

PMID- 9153615
TI  - A neurological complication of inferior petrosal sinus sampling during
      investigation for Cushing's disease: a case report.
AB  - A 45 year old woman with hirsutism was found to have classic biochemical features
      of ACTH dependent Cushing's disease, with partial cortisol suppression in
      response to dexamethasone. As no pituitary adenoma could be visualised by CT or
      MRI, she proceeded to bilateral simultaneous inferior petrosal sinus sampling
      before possible surgery. During the course of this procedure she had a stroke
      affecting the brainstem at the level of the pontocerebellar junction. This
      complication of petrosal sinus sampling has been previously described but is not
      widely recognised; the procedure should only be undertaken when results of less
      invasive tests are equivocal.

PMID- 9153616
TI  - Treatment of acute pandysautonomia with intravenous immunoglobulin.
AB  - Acute pandysautonomia has been suggested to be an uncommon variant of Guillain
      Barre syndrome. Acute pandysautonomia does not seem to have been treated with
      intravenous immunoglobulin or other therapies proved efficacious in Guillain
      Barre syndrome. A patient is reported with severe acute pandysautonomia who
      responded dramatically to intravenous immunoglobulin. The findings are consistent
      with a dysimmune pathogenesis for this syndrome and suggest a possible treatment
      for future cases.

PMID- 9153617
TI  - Computed tomographic analysis of hemifacial spasm: narrowing of the posterior
      fossa as a possible facilitating factor for neurovascular compression.
AB  - Hemifacial spasm can be caused by vascular compression of the facial nerve at the
      root exit zone from the brainstem. Several case reports suggest that narrowing of
      the cerebellopontine angle cistern caused by Paget's disease, abnormal elevation
      of the petrous bone caused by hyperplasia, or contralateral acoustic neurinoma
      may increase the chance of vascular compression of the facial nerve. Therefore,
      posterior fossa narrowness has been evaluated in 34 patients with hemifacial
      spasm by measuring the petrous angle and pons diameter index to elucidate whether
      narrowing of the posterior fossa can act as a facilitating factor for
      neurovascular compression. The petrous angle in the hemifacial spasm group was
      significantly smaller than that in the control group, which consisted of 33
      patients with an unruptured supratentorial aneurysm, and the pons diameter index
      in the hemifacial spasm group was significantly greater than that in the control
      group. These results indicate that the cerebellopontine angle cistern of patients
      with hemifacial spasm is narrower resulting in more crowded cranial nerves and
      vascular structures compared with patients without hemifacial spasm. The
      narrowness of the cerebellopontine angle cistern may be a possible factor in
      facilitating neurovascular compression in hemifacial spasm.

PMID- 9153618
TI  - Maternal transmission in sporadic Huntington's disease.
AB  - Huntington's disease is an autosomal dominant neurodegenerative disorder caused
      by the expansion of a (CAG)n repeat in the IT15 gene. Three per cent of cases are
      sporadic and in those in which family studies have been performed, the origin of
      the mutation was always paternal. The first sporadic case of Huntington's disease
      is presented in which a premutated maternal allele of 37 CAG repeats was
      transmitted expanded to the proband (43 CAG repeats). Molecular analysis of the
      IT15 gene is extremely important in sporadic cases of Huntington's disease,
      providing correct diagnosis of the disorder and facilitating genetic counselling
      to the family members.

PMID- 9153619
TI  - Gaze related enhancement of hemispheric blood flow in a stroke patient.
AB  - OBJECTIVE: A patient with a right posterior cerebral artery territory infarction
      and a left superior quadrantanopia exhibited improvement on various visual tasks
      including Goldmann perimetry during extreme right gaze. The phenomenon was
      investigated by functional imaging of cerebral blood flow. METHODS:
      [(99m)Tc]HMPAO SPECT was carried out while the patient gazed to the right and to
      the left at an 8 Hz flash stimulus. RESULTS: When compared with left gaze, photic
      stimulation during right gaze was associated with an up to 39.8% increase in
      regional cerebral blood flow in the damaged right hemisphere, including
      Brodmann's areas 3-1-2, 7, 21, 22, 39, and 40. CONCLUSIONS: These gaze related
      alterations in function and synaptic activity suggest the engagement of a novel
      arousal-like mechanism that may account in part for comparable findings in
      patients with neglect and other disorders, and may have relevance to
      rehabilitation.

PMID- 9153620
TI  - Creutzfeldt-Jakob disease and stress.

PMID- 9153621
TI  - Wasting, weakness, and the MRC scale in the first dorsal interosseous muscle.

PMID- 9153622
TI  - Management of parkinsonism and psychotic depression in a case of acute
      intermittent porphyria.

PMID- 9153624
TI  - Playing piano in visuospatial neglect: a case study.

PMID- 9153623
TI  - A case of Machado-Joseph disease presenting with spastic paraparesis.

PMID- 9153625
TI  - Two unusual clinical presentations of the mitochondrial DNA A3243G point mutation
      in adult neurological practice.

PMID- 9153626
TI  - Brain and spinal cord MRI in motor neuron disease.

PMID- 9153627
TI  - The musical brain: brain waves reveal the neurophysiological basis of musicality
      in human subjects.
AB  - To reveal neurophysiological prerequisites of musicality, auditory event-related
      potentials (ERPs) were recorded from musical and non-musical subjects, musicality
      being here defined as the ability to temporally structure auditory information.
      Instructed to read a book and to ignore sounds, subjects were presented with a
      repetitive sound pattern with occasional changes in its temporal structure. The
      mismatch negativity (MMN) component of ERPs, indexing the cortical preattentive
      detection of change in these stimulus patterns, was larger in amplitude in
      musical than non-musical subjects. This amplitude enhancement, indicating more
      accurate sensory memory function in musical subjects, suggests that even the
      cognitive component of musicality, traditionally regarded as depending on
      attention-related brain processes, in fact, is based on neural mechanisms present
      already at the preattentive level.

PMID- 9153628
TI  - Posturo-kinetic effects on kicking movements of a lack of initial ground support
      under the moving leg.
AB  - The posturo-kinetic effects of having no initial ground support under the
      movement leg were studied during kicking movements. Considerable effects were
      observed on the efficiency of the voluntary movement, which was noticeably
      reduced, as well as on the organisation of the postural adjustments. The fact
      that the efficiency of the movement was lower than under normal conditions shows
      that the posturo-kinetic reorganisation does not succeed in compensating for the
      lack of initial thrust of the foot against the floor. These results underline the
      important contribution of the postural adjustments to the performance of the
      movement itself, besides their role in maintaining equilibrium and posture.

PMID- 9153629
TI  - Effects of histamine on neuropeptide release into the knee joint perfusate and
      cerebrospinal fluid in rats.
AB  - In the present study we examined the effect of histamine injection on
      neuropeptide release in vivo in rats. Rats were injected with histamine either
      into the left knee joint or intraperitoneally. Concentrations of substance P (SP)
      , neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y
      (NPY)-like immunoreactivity (-LI) were examined in the knee joint perfusates and
      cerebrospinal fluid at 2, 6 and 24 h following injection, by radioimmunoassay.
      Results show that intraarticular injection of histamine induced a bilateral
      release of SP-, NKA- and CGRP-LI in the knee joint perfusates while
      intraperitoneal injection of histamine induced a release of SP-, NKA- and CGRP-LI
      into the cerebrospinal fluid. No changes in concentrations of NPY-LI were
      observed following histamine injection. Results of the present study indicate
      that histamine selectively stimulates sensory neurons without affecting
      sympathetic. The increased concentrations of sensory neuropeptide-LI in the
      cerebrospinal fluid following intraperitoneal administration of histamine
      indicate a new mechanism by which histamine may exert systemic effects during
      inflammation and allergy.

PMID- 9153630
TI  - Non-linear analysis of emotion EEG: calculation of Kolmogorov entropy and the
      principal Lyapunov exponent.
AB  - For 76 healthy subjects, two non-linear measures, capturing the dynamical
      properties of the system orbiting within the attractor (i.e. Kolmogorov entropy,
      K2 and principal Lyapunov exponent, L1), were calculated from EEG segments,
      corresponding to different states of brain activity, induced by emotionally
      valenced (i.e. neutral, affective positive and negative) video stimuli.
      Significantly elevated values of EEG K2 and L1 in response to both positive and
      negative film categories as compared to neutral one were evidenced. Relying on
      the obtained findings, it is suggested that increased cortical dynamics, up to a
      certain level, are probably necessary for emotion functioning.

PMID- 9153632
TI  - Chronic administration of DL-allyl-glycine into the neostriatum, disorganises the
      firing modes of the nigral dopaminergic neurons in the rat.
AB  - Nigral dopaminergic (DA) neurons have been reported to fire according to three
      modes: very regular (pacemaker 42%) irregular (random 46%) and bursty (12%). The
      switch from simple spiking mode (pacemaker or random) to bursty firing would
      correspond to an increase in DA release necessary for the performance of a new
      motor act. As nigral DA cells are impinged upon by a high percentage of GABAergic
      afferents we blocked striatal GABAergic output neurons by chronic administration
      into the neostriatum of allyl-glycine, a glutamic acid decarboxylase (GAD)
      inhibitor. After treatment, rats presented hyperkinesia and hypertonia on the
      injected side and recordings showed a drastic change in the percentage
      distribution of nigral DA cell discharge patterns; 85% were 'random', 12%
      'pacemaker' and 3% bursty. Such a disturbance, by impeding adapted DA release,
      may account for the hyperkinetic and dystonic disorders observed.

PMID- 9153631
TI  - Histamine (H1) receptor antagonist inhibits leukocyte rolling in pial vessels in
      the early phase of bacterial meningitis in rats.
AB  - The present study tested the hypothesis whether a histamine dependent pathway is
      involved in leukocyte-endothel interaction in the early phase of bacterial
      meningitis. Using confocal laser scanning microscopy we investigated leukocyte
      rolling in brain venules in vivo during 4 h in experimental pneumococcal
      meningitis in the rat. Leukocyte rolling, but not firm adhesion induced by
      intracisternally (i.c.) injected pneumococcal cell wall components, was
      temporarily inhibited (2 h, 5.6 +/- 1.9 vs. 2.3 +/- 0.9; 3 h, 7.4 +/- 2.7 vs. 3.1
      +/- 1.3/100 microm/min) by diphenhydramine, a histamine H1 receptor antagonist.
      Histamine, possibly released by activated mast cells, is known to initiate P
      selectin upregulation and subsequent leukocyte rolling. This data suggest that
      histamine is a mediator of leukocyte rolling in the early phase of bacterial
      meningitis.

PMID- 9153633
TI  - Effects of N-methyl-D-aspartate-receptor blockade on high-potassium-induced
      neuronal death and glutamate release.
AB  - Microdialysis probe delivery of an isotonic high-K+ solution to the rat amygdala
      for 60-70 min produces neuronal necrosis, edematous neuropil and increases in
      extracellular glutamate and aspartate. In this study we determined the effects of
      the competitive N-methyl-D-aspartate (NMDA)-receptor antagonist CGP 40116.
      Bilateral microdialysis probes were inserted through previously placed guide
      cannulae in the basolateral amygdaloid nuclei of adult Wistar rats. Following a 2
      h baseline perfusion in freely-moving rats, the solution was switched bilaterally
      for 60-70 min to an isotonic 100 mM K+ solution; 12% of the 100 mM K+ is
      extracted by tissue. One side contained either 36 or 360 microM CGP 40116 during
      baseline and high-K+ perfusion, of which 42 and 48% were extracted respectively.
      Although neither concentration reduced tissue edema, 360 microM CGP 40116 was
      neuroprotective and prevented the high-K+-induced elevations of glutamate.

PMID- 9153634
TI  - Regulation of immunolabelled mu-opioid receptors and protein kinase C-alpha and
      zeta isoforms in the frontal cortex of human opiate addicts.
AB  - To assess the status of opioid receptors in the human brain during the process of
      opiate addiction, the abundance of immunoreactive mu-opioid receptors was
      quantitated in postmortem brains of chronic opiate addicts who had died of a
      heroin or methadone overdose. The immunoreactive levels of the associated enzyme
      protein kinase C (PKC-alpha and zeta isoforms) and G proteins (G alpha(i1/2)
      subunits) were also assessed in the same brains. In the frontal cortex of opiate
      addicts, the abundance of mu-opioid receptors was not different from that
      obtained in matched controls. The level of Ca2+-dependent PKC-alpha was decreased
      (25%), whereas that of the atypical PKC-zeta remained unchanged. The density of G
      alpha(i1/2) proteins also was found to be increased (40%). The results indicate
      that opiate addiction in humans does not appear to be associated with a reduced
      density of brain mu-opioid receptors. The sustained down-regulation of PKC-alpha
      in the brain of opiate addicts would allow the up-regulation of G alpha(i1/2)
      proteins aimed at compensating the postulated desensitization of the mu-opioid
      receptor system.

PMID- 9153635
TI  - The biphasic opening of the blood-brain barrier in the cortex and hippocampus
      after traumatic brain injury in rats.
AB  - This study examined the time course of the blood-brain barrier (BBB) opening and
      correlated this with brain edema formation after a lateral controlled cortical
      impact (CCI) brain injury in rats. Quantitative measurement of Evans blue (EB)
      extravasation using fluorescence was employed at 2, 4, 6 h and 1, 2, 3, 4 and 7
      days after injury. Brain edema was measured by specific gravity of the tissue at
      corresponding time points. Two prominent EB extravasations were observed at 4-6 h
      and 3-day after injury in the injury-site cortex and the ipsilateral hippocampus.
      Brain edema became progressively more severe over time and peaked at 24 h after
      injury and began to decline after day 3. These results suggest that there is a
      biphasic opening of the BBB after CCI brain injury and the second opening of the
      BBB does not contribute to a further increase in edema formation.

PMID- 9153636
TI  - Decreased beta-adrenoceptor-stimulated adenylyl cyclase activity in lymphocytes
      from Alzheimer's disease patients.
AB  - Previous studies have shown that in Alzheimer's disease post-mortem brain there
      are disruptions of both beta1-adrenoceptor-G-protein coupling and G-protein
      stimulation of adenylyl cyclase activity. Decreased beta-adrenoceptor stimulated
      adenylyl cyclase activity has also been shown in Alzheimer's disease primary skin
      fibroblasts. In the present study, we determined the regulation of adenylyl
      cyclase in Alzheimer's disease patients using an easily accessible tissue source,
      namely peripheral blood lymphocytes. beta-Adrenoceptor- and forskolin-stimulated
      adenylyl cyclase activities were investigated in lymphocytes from 12 Alzheimer's
      disease and 12 carefully matched and selected control subjects. No significant
      differences were found in basal or forskolin-stimulated enzyme activities between
      Alzheimer's disease and control lymphocytes. In contrast, isoprenaline-stimulated
      adenylyl cyclase activities were significantly lower in the Alzheimer's disease
      groups, as compared to controls. These results indicate that there is a
      widespread disruption of beta-adrenoceptor-G-protein-enzyme coupling in different
      tissues from Alzheimer's disease patients, and that adenylyl cyclase disturbances
      previously reported in Alzheimer's disease brain do not occur as a consequence of
      disease pathology or of terminal illness.

PMID- 9153637
TI  - Serum uncouples elevation of cyclic adenosine monophosphate concentration from
      cyclic adenosine monophosphate dependent morphological changes exhibited by
      cultured pituicytes.
AB  - Cultured pituicytes (neurohypophysial astrocytes) are normally flat amorphous
      cells when incubated (90 min) in a HEPES balanced salt solution (HBSS) but become
      stellate when incubated in HBSS supplemented with forskolin. This stellation
      process is attenuated by serum (0.5% vol/vol). The experiments described here
      were designed to determine whether serum attenuates stellation by modulation of
      the intracellular cyclic adenosine monophosphate (cAMP) concentration or some
      other mechanism. It was observed that the effect of serum on forskolin-induced
      stellation was not affected by pertussis toxin (100 ng/ml) and that serum also
      inhibited stellation induced by the phosphodiesterase inhibitor 3-isobutyl-1
      methylxanthine (IBMX; 100 microM). Further, serum inhibited stellation induced by
      the membrane permeable cAMP analog 8-bromo cAMP (150 microM). These results
      indicate that although an increase of intracellular cAMP concentration is
      necessary for pituicyte stellation, an increase of intracellular cAMP
      concentration may be decoupled from stellation.

PMID- 9153638
TI  - Glycosylation of cholinesterase forms in brain from normal and dystrophic Lama2dy
      mice.
AB  - Differences in the oligosaccharides attached to acetyl- (AChE) and
      butyrylcholinesterase (BuChE) forms in brain from control and merosin-deficient
      Lama2dy dystrophic mice were investigated by means of their interaction with
      agarose-immobilized lectins. Asymmetric AChE, hydrophilic and amphiphilic AChE
      and BuChE tetramers, and amphiphilic AChE and BuChE monomers were identified in
      brain. All ChE forms were strongly adsorbed to the lectins concanavalin A (Con
      A), Lens culinaris (LCA) and Triticum vulgaris (WGA), and poorly so to Ricinus
      communis agglutinin (RCA), suggesting that the oligosaccharides in AChE or BuChE
      subunits are similarly processed regardless of their state of polymerization. The
      lack of differences in the interaction of lectins with homologous AChE and BuChE
      forms in normal and dystrophic tissue indicates that, in contrast to ChEs forms
      in skeletal muscle, the dystrophic condition does not disturb the processing of
      the oligosaccarides of brain enzyme forms.

PMID- 9153639
TI  - Multichannel EEG fields during and without visual input: frequency domain model
      source locations and dimensional complexities.
AB  - 27-Channel EEG potential map series were recorded from 12 normals with closed and
      open eyes. Intracerebral dipole model source locations in the frequency domain
      were computed. Eye opening (visual input) caused centralization (convergence and
      elevation) of the source locations of the seven frequency bands, indicative of
      generalized activity; especially, there was clear anteriorization of alpha-2
      (10.5-12 Hz) and beta-2 (18.5-21 Hz) sources (alpha-2 also to the left).
      Complexity of the map series' trajectories in state space (assessed by Global
      Dimensional Complexity and Global OMEGA Complexity) increased significantly with
      eye opening, indicative of more independent, parallel, active processes. Contrary
      to PET and fMRI, these results suggest that brain activity is more distributed
      and independent during visual input than after eye closing (when it is more
      localized and more posterior).

PMID- 9153640
TI  - Dissociative expression of adenoviral-mediated E. coli LacZ gene between ischemic
      and reperfused rat brains.
AB  - A replication-defective adenoviral vector containing the E. coli lacZ gene was
      directly injected into the ischemic or reperfused cerebral cortex of rats. An
      administration of adenoviral vector showed a slight to moderate expression of the
      lacZ gene in the cerebral cortex of the middle cerebral artery (MCA) region until
      2 days after the MCA occlusion. In contrast, expression of the lacZ gene was not
      observed, or only minimally so, in the reperfused brain until 2 days after a 90
      min of transient MCA occlusion. However, the lacZ expression dramatically
      increased at 7 days after the reperfusion, then diminished by 21 days. The
      majority of brain cells that expressed the lacZ gene were neurons and a fraction
      (5-10%) were astroglial cells. The present study showed that an exogenous gene
      was transferred and expressed in neural cells of ischemic and reperfused brains
      in vivo, but the temporal profile of the expression is dissociative.

PMID- 9153641
TI  - The relationship between monkey hippocampus place-related neural activity and
      action in space.
AB  - To solve complex spatial problems like visual scanning and spatial navigation,
      animals must explore and actively sense an array of environmental stimuli. Recent
      studies have led to an agreement that the hippocampal formation (HF) is essential
      to the internal representation of spatial relation in animals. In the present
      study, neural activity was recorded from the HF of three monkeys, which steered a
      cab to various locations by pressing the appropriate bars (spatial moving task).
      Place-related activity of most HF neurons persisted even if the direction the
      monkey faced was rotated during the task. However, when the experimenter, rather
      than the monkey, controlled the device, the place-related neural activity of most
      HF neurons turned out to be obscure. The results suggest that the HF represents
      space effectively in situations in which the animal acts in space.

PMID- 9153642
TI  - Effects of an anabolic-androgenic steroid on the regulation of the NMDA receptor
      NR1, NR2A and NR2B subunit mRNAs in brain regions of the male rat.
AB  - The expression of the N-methyl-D-aspartate (NMDA) receptor subunits NR1, NR2A and
      NR2B mRNAs was examined in discrete areas of the male rat brain (including
      hippocampus, hypothalamus, nucleus accumbens and cortex) following 14 days daily
      intramuscular injections of high doses (5 and 15 mg/kg) of an anabolic-androgenic
      steroid (AAS) (nandrolone decanoate). The results indicated that the drug
      produced a significant decrease in the mRNA expression of the NR2A receptor
      subunit both in the hypothalamus and hippocampus. A decrease in the level of NR2B
      receptor mRNA was observed in hypothalamus at the lower dose of the AAS but in
      other areas examined, this receptor subunit mRNA was not affected. Except for a
      decreased expression in the nucleus accumbens at the higher dose of AAS the NR1
      receptor subunit mRNA was not affected by the drug. The three subunit mRNAs in
      cortex were not significantly altered. The effects of the steroid on the mRNA
      expression for the NMDA receptor subunits in hippocampus and hypothalamus are
      suggested to be involved in the mechanism behind aggressive behaviour, a feature
      previously associated with AAS misuse. The downregulation of the mRNA for the NR1
      receptor subunit in nucleus accumbens may relate to a mechanism involved in the
      recently suggested AAS-induced stimulation of the brain reward system.

PMID- 9153644
TI  - Inhibition of glutamate decarboxylase activity by 3-mercaptopropionic acid has
      different time course in the immature and adult rat brains.
AB  - It has been found that the latency of epileptic seizures caused by glutamate
      decarboxylase (GAD) inhibitor 3-mercaptopropionate (3-MPA) is markedly longer in
      immature rats than in the adults. Time course of rat brain GAD inhibition was
      studied in 12-day-old and adult (90-day-old) animals following 3-MPA (70 mg/kg
      i.p.). GAD activity was determined by quantification of 14CO2 liberated from [1
      (14)C]glutamate by supernatant 20,000 x g of brain homogenate prepared from rats
      killed at different intervals after 3-MPA administration. In adult rats, the
      enzyme activity decreased significantly by 14.1% even 1 min after 3-MPA
      administration and was decreasing gradually till the onset of seizures. In
      immature rats, GAD activity decrease after 1 min was by 41.4% and further
      decrease was smaller. Comparison of the time profiles of GAD changes in both
      groups confirmed our findings that in spite of delayed seizure onset, GAD
      inhibition in immature rats is more pronounced, probably due to immaturity of the
      blood-brain barrier.

PMID- 9153643
TI  - The apolipoprotein E epsilon4 allele frequency is normal in fronto-temporal
      dementia, but correlates with age at onset of disease.
AB  - The apolipoprotein (apoE) epsilon4 allele was studied in fronto-temporal dementia
      (FTD), a diagnostic category including the specific disorders Pick's disease and
      frontal lobe degeneration of non-Alzheimer type (FLD). These dementing diseases
      have neuronal and synaptic degeneration in common with Alzheimer's disease (AD),
      for which the presence of the apoE epsilon4 allele is a known risk factor, and
      lowers the age of onset of disease. Previous studies on the apoE epsilon4 allele
      frequency in FTD have been inconclusive. The structural hallmarks of AD,
      allegedly linked to apoE presentation, neuritic plaques (NP), primarily composed
      of aggregates of beta-amyloid, and neurofibrillary tangles (NFT), primarily
      composed of hyperphosphorylated tau, are lacking in FTD. However, tau-positive
      cytoskeletal pathology is found in Pick's disease, but not in FLD. Resolving
      whether the epsilon4 frequency is increased in FTD or not may thus give clues to
      the pathogenetic mechanism of apoE in AD. We therefore studied apoE alleles in a
      well characterized material of FTD patients. The epsilon4 allele frequency was
      similar in 25 patients with FTD (14.0%) as compared with 26 healthy controls
      (13.5%). A post-mortem neuropathological examination was performed in 10 cases
      (nine had FLD and one Pick's disease). Our finding of a normal epsilon4 allele
      frequency in our group of FTD, principally consisting of FLD cases, support
      hypotheses involving differential binding of apoE to beta-amyloid and/or tau, in
      the development of beta-amyloid deposition and NP formation and/or tau
      hyperphosphorylation and NFT formation, for the pathogenetic role of apoE in AD.
      The age at onset was significantly lower (P < 0.01) in FTD patients possessing
      the epsilon4 allele (48.7 +/- 8.0 years) than in patients not possessing this
      allele (58.9 +/- 7.6 years). We conclude that, although the apoE epsilon4 allele
      frequency is not increase in FTD, the epsilon4 allele is not an etiological
      factor, but may rather be an accelerating factor in the degenerative process of
      FTD, thereby resulting in an earlier presentation of the disorder in individuals
      predisposed to develop FTD.

PMID- 9153645
TI  - Evidence for colocalization of calcineurin and calcium channels in dorsal root
      ganglion neurons.
AB  - Calcineurin is a serine/threonine protein phosphatase 2B widely distributed in
      the brain. However, its role in brain function remains unknown. Recent data
      indicate that calcineurin can participate in long-term depression or long-term
      potentiation in rat hippocampus. Obviously, calcineurin can also be involved in
      numerous brain diseases, such as ischaemic hippocampal damage when the protein
      dephosphorylation system is markedly altered and hyperphosphorylation of the
      microtubule system in Alzheimer's disease. Besides, abnormal phosphorylation of
      the cytoskeletal proteins affecting the synaptic signalling can lead to different
      pathological disorders in the brain. In this study we analysed in more detail the
      localization of calcineurin in neuronal elements by using confocal microscopy and
      immunocytochemical approaches to record the enzyme expression in cultured rat
      dorsal root ganglion neurons. This is the first report showing that calcineurin
      immunoreactivity is highly expressed in dorsal root ganglion neurons and it is
      localized mainly near the inner surface of the plasma membrane. Immunostaining of
      these cells by anti-beta subunits of voltage-operated Ca2+ channels showed that
      distribution of calcium channel beta-subunit and calcineurin is very similar. Our
      findings confirm that the function of calcineurin can be directly connected with
      the activity of voltage-operated calcium channels.

PMID- 9153646
TI  - A cellular mechanism for the neuronal changes underlying Alzheimer's disease.

PMID- 9153647
TI  - Cell loss in the nucleus basalis is related to regional cortical atrophy in
      Alzheimer's disease.
AB  - Cortical atrophy and cell loss in the cholinergic nucleus basalis is a well
      established characteristic of Alzheimer's disease; however, previous studies not
      have analysed cholinergic cell loss and cortical atrophy in concert. In autopsy
      brains from eight patients with Alzheimer's disease and 12 control subjects, the
      numbers of nucleus basalis neurons were determined from 50-microm serial Nissl
      stained sections. Volumes of the cerebrum, cortical gray matter (total, lobar and
      subregional), white matter and deep gray structures were computed by point
      counting on black and white photographs of gapless 3-mm coronal slices of
      formalin-fixed brains. Cell loss in the nucleus basalis was found to range
      between 89% and 42% in Alzheimer's disease compared with controls. White matter
      volume was unchanged in absolute terms in Alzheimer's disease patients compared
      with controls, while cortical volume was significantly reduced. Gray matter
      atrophy was most prominent in temporal and frontal cortices. A highly significant
      linear relationship was found between cortical volume and nucleus basalis cell
      number in controls and Alzheimer's disease patients, with values for both groups
      on a single regression line. Whole brain and cerebral volumes were also highly
      correlated to nucleus basalis cell numbers in both groups. A quantitative
      analysis of plaque and tangle burden in cortical target areas of the nucleus
      basalis was performed. In contrast to the relationship with cortical volume,
      nucleus basalis cell number and neurofibrillary tangle number were not
      significantly correlated to the density of cortical histopathology. These results
      suggest that the volume of cortical gray matter is coupled to the number of
      nucleus basalis neurons. Compromised viability of nucleus basalis neurons may
      precede cortical volume loss as large numbers of neurofibrillary tangles,
      detected with nickel peroxidase staining, were found in this nucleus in all
      Alzheimer's disease cases, including those with minimal cell loss.

PMID- 9153648
TI  - Chronic corticosterone treatment induces parallel changes in N-methyl-D-aspartate
      receptor subunit messenger RNA levels and antagonist binding sites in the
      hippocampus.
AB  - Some of the effects of glucocorticoids on the function and neuronal plasticity of
      the hippocampus are mediated by N-methyl-D-aspartate receptor activation. We
      tested the hypothesis that chronic corticosterone administration increases N
      methyl-D-aspartate receptor expression in the hippocampus of the rat. We used in
      situ hybridization histochemistry to measure the messenger RNA levels for the
      NR1, NR2A and NR2B subunits of the N-methyl-D-aspartate receptor and
      [3H]dizocilpine maleate (a non-competitive antagonist) binding to measure N
      methyl-D-aspartate receptor density. Since corticosterone depresses circulating
      testosterone levels, we also examined whether the effects of corticosterone are
      mediated by or interact with the effects of testosterone. In the intact animal,
      corticosterone increased messenger RNA levels for NR2A and NR2B but not NR1
      subunits of the N-methyl-D-aspartate receptor in all regions of the hippocampus.
      Testosterone had no significant effect on messenger RNA levels of any of the
      subunits. The subunit composition determines the functional and pharmacological
      properties of the N-methyl-D-aspartate receptor. We used ifenprodil inhibition of
      [3H]dizocilpine maleate binding, which has been used to distinguish NR2A- from
      NR2B-containing receptors, to determine whether corticosterone altered the
      proportion of high- and low-affinity sites for ifenprodil in parallel with the
      changes in subunit messenger RNA levels. Corticosterone increased the density of
      [3H]dizocilpine maleate binding sites without changing the dissociation constant
      for [3H]dizocilpine maleate or the proportion of high- and low-affinity sites for
      ifenprodil. These data suggest that the effects of corticosterone on hippocampal
      function are mediated, in part, by parallel increases in NR2A and NR2B subunit
      levels and the number of receptor channel binding sites.

PMID- 9153650
TI  - Calcineurin in the adult rat hippocampus: different distribution in CA1 and CA3
      subfields.
AB  - We examined the immunohistochemical regional distribution of calcineurin
      (Ca2+/calmodulin-dependent protein phosphatase) in the adult rat hippocampus,
      following various regional destruction. In the normal adult rat hippocampus, the
      calcineurin immunoreactivity showed a characteristic pattern. This protein
      phosphatase was detected in all layers of the CA1 subfield, including the
      cytoplasm of the pyramidal cells, whereas it was strongly evident in the stratum
      lucidum and moderately so in the cytoplasm of pyramidal cells in the CA3
      subfield. Seven days after transient forebrain ischemia, which induced
      destruction of CA1 pyramidal cells, the calcineurin immunoreactivity decreased in
      all layers of the CA1 subfield, while the immunoreactivity for synapsin I, a
      marker of the presynaptic site, was preserved. Seven days after the
      intraventricular injection of kainate, which induced destruction of CA3 pyramidal
      cells, the calcineurin immunoreactivity in the stratum lucidum was preserved,
      although the immunostaining pattern of the stratum lucidum changed when CA3
      pyramidal cells were destroyed. Seven days after mechanical destruction of the
      dentate gyrus and CA4 subfield, which induced destruction of mossy fibers, the
      calcineurin immunoreactivity in the stratum lucidum was lost, except in the far
      site of the stratum lucidum. In the CA1 subfield, calcineurin was mainly located
      in postsynaptic sites, while it was mainly located in the presynaptic sites in
      the mossy fibers of the CA3 subfield. The immunohistochemistry of adjacent
      sections with antibodies of microtubule-associated protein 2 and synapsin I,
      which are markers of postsynaptic and presynaptic sites respectively, supports
      these results. Thus, calcineurin has a different synaptical distribution in the
      rat hippocampus.

PMID- 9153651
TI  - Triple immunosuppression protects murine intracerebral, hippocampal xenografts in
      adult rat hosts: effects on cellular infiltration, major histocompatibility
      complex antigen induction and blood-brain barrier leakage.
AB  - Recently we reported protection of intracerebral mouse to rat hippocampal
      xenografts upon treatment with a combination of cyclosporin A, prednisolone and
      azathioprine. These findings are now supported in an extended analysis of graft
      infiltrating cells. Host T-cell and macrophage infiltration and the
      immunocytochemical level of cellular expression of major histocompatibility
      complex class I and II antigens, measured by densitometric analysis, were
      compared between recipient rats receiving cyclosporin A alone or cyclosporin A in
      combination with prednisolone and azathioprine. The combination therapy resulted
      in a much improved survival of the xenografted hippocampal tissue with
      preservation of organotypic granule and pyramidal cell layers. Graft infiltration
      by T-cells and macrophages was significantly lower and the level of major
      histocompatibility complex class I and II antigen expression by the infiltrating
      cells markedly reduced. Lower expression of donor-type major histocompatibility
      complex class I antigen was also found in the xenografts in the trimedicated
      recipients, together with reduced blood brain barrier leakage and astrogliosis at
      the host-graft interface. The results demonstrate the benefits of using combined
      immunosuppressive strategies for protection of histoincompatible brain xenografts
      in the central nervous system.

PMID- 9153649
TI  - Corticosteroid effects on sodium and calcium currents in acutely dissociated rat
      CA1 hippocampal neurons.
AB  - Consequences of corticosteroid receptor activation on voltage-dependent Na+
      conductances were studied in acutely dissociated CA1 hippocampal neurons. This
      preparation was selected because of the compact electrotonic properties of
      dissociated neurons, allowing reliable voltage-clamp of the large and fast Na+
      currents. The Na+ currents were studied in (i) neurons of adrenalectomized
      animals (no steroid receptors occupied), (ii) neurons from tissue of
      adrenalectomized rats treated in vitro with corticosterone and the glucocorticoid
      receptor antagonist RU38486 (selectively occupying the mineralocorticoid
      receptor), (iii) corticosterone-treated neurons of adrenalectomized animals
      (occupying both the mineralocorticoid and glucocorticoid receptors) and (iv)
      neurons of sham-operated animals. Activation and steady-state inactivation
      properties of the Na+ current recorded in neurons of adrenalectomized animals
      were slightly shifted (3-5 mV) to hyperpolarized potentials as compared to the
      Na+ currents from neurons of the other experimental groups. Furthermore, the
      removal from inactivation of the Na+ current in the group of neurons of
      adrenalectomized animals was relatively slow. Although small, these effects could
      influence neuronal properties like action potential generation and accommodation.
      Under the present experimental conditions, no apparent differences were seen
      between cells with predominant mineralocorticoid receptor activation and cells
      where both mineralocorticoid and glucocorticoid receptors were occupied. In
      contrast to Na+ currents, voltage-dependent Ca2+ currents displayed no steroid
      dependent shifts in voltage-dependent properties. However, Ca2+ current
      amplitudes were increased by approximately 160% in CA1 neurons of
      adrenalectomized animals as compared to Ca2+ currents from neurons of the other
      experimental groups. We conclude that corticosteroid receptor activation affects
      various properties of voltage-dependent Na+ and Ca2+ conductances in CA1 neurons,
      indicating that the steroid receptors are involved in the modulation of neuronal
      excitability in these cells.

PMID- 9153652
TI  - Intrastriatal grafts of embryonic mesencephalic rat neurons genetically modified
      using an adenovirus encoding human Cu/Zn superoxide dismutase.
AB  - Intrastriatal grafting of embryonic dopamine-containing neurons is a promising
      approach for treating clinical and experimental Parkinson's disease. However,
      neuropathological analyses of grafted patients and transplanted rats have
      demonstrated that the survival of grafted dopamine neurons is relatively poor. In
      the present study, we pursued a strategy of transferring a potentially
      neuroprotective gene into rat embryonic mesencephalic rat cells in vitro, before
      grafting them into the denervated striatum of 6-hydroxydopamine-lesioned rats. We
      performed intrastriatal grafts of embryonic day 14 mesencephalic cells infected
      with replication-defective adenoviruses bearing either the human copper-zinc
      superoxide dismutase gene or, as a control, the E. coli lac Z marker gene. The
      transgenes were expressed in the grafts four days after transplantation and the
      expression persisted for at least five weeks thereafter. After five weeks
      postgrafting, there was more extensive functional recovery in the superoxide
      dismutase group as compared to the control (uninfected cells) and beta
      galactosidase groups. The functional recovery was significantly correlated with
      the number of tyrosine hydroxylase-positive cells in the grafts, although the
      clear trend to increased survival of the dopamine neurons in the superoxide
      dismutase grafts did not reach statistical significance. Only a moderate
      inflammatory reaction was revealed by OX-42 immunostaining in all groups,
      suggesting that ex vivo gene transfer using adenoviral vectors is a promising
      method for delivering functional proteins into brain grafts.

PMID- 9153653
TI  - Topographical organization of projections from the entorhinal cortex to the
      striatum of the rat.
AB  - The efferent projections of the entorhinal cortex to the striatum were studied
      with retrograde (horseradish peroxidase wheat germ agglutinin) and anterograde
      (biocytin and biotinylated dextran amine) tracing methods. The bulk of the
      entorhinal cortical fibres were found to project to the nucleus accumbens in the
      ventral striatum, but the caudate putamen is only sparsely and diffusely
      innervated, rostrally, along its dorsal and medial borders. Fibres arising from
      neurons in the lateral entorhinal cortex project throughout the rostrocaudal
      extent of the nucleus accumbens but are most abundant in the core and lateral
      shell of that nucleus. The rostral neurons of the medial entorhinal cortex were
      found to project sparsely to the striatum, whereas caudal neurons provide a dense
      input to the rostral one-third of the nucleus accumbens, especially to the
      rostral pole, where they concentrate more in the core than in the shell.
      Contralateral entorhinal projections, which are very sparse, were found in the
      same parts of the nucleus accumbens and the caudate-putamen as the ipsilateral
      terminal fields. The present observations that entorhinal inputs to the nucleus
      accumbens are regionally aligned suggest that disruption of these connections
      could produce site-specific deficits with, presumably, specific behavioural
      consequences.

PMID- 9153654
TI  - Cholinergic responses of morphologically and electrophysiologically characterized
      neurons of the basolateral complex in rat amygdala slices.
AB  - The electrophysiological properties, the response to cholinergic agonists and the
      morphological characteristics of neurons of the basolateral complex were
      investigated in rat amygdala slices. We have defined three types of cells
      according to the morphological characteristics and the response to depolarizing
      pulses. Sixty-six of the recorded cells (71%) responded with two to three action
      potentials, the second onwards having less amplitude and longer duration (burst).
      In a second group, consisting of 21 cells (22%), the response to depolarization
      was a train of spikes, all with the same amplitude (multiple spike). Finally,
      seven neurons (7%) showed a single action potential (single spike). Burst
      response and multiple-spike neurons respond to the cholinergic agonist carbachol
      (10-20 microM) with a depolarization that usually attained the level of firing.
      This effect was accompanied by decreased or unchanged input membrane resistance
      and was blocked by atropine (1.5 microM). The depolarizing response to
      superfusion with carbachol occurred even when synaptic transmission was blocked
      by tetrodotoxin, indicating a direct effect of carbachol. Similarly, the
      depolarization by carbachol was still present when the M-type conductance was
      blocked by 2 mM Ba2+. The carbachol-induced depolarization was prevented by
      superfusion with tetraethylammonium (5 mM). Injection of biocytin into some of
      the recorded cells and subsequent morphological reconstruction showed that
      "burst" cells have piriform or oval cell bodies with four or five main dendritic
      trunks; spines are sparse or absent on primary dendrites but abundant on
      secondary and tertiary dendrites. This cellular type corresponds to a pyramidal
      morphology. The "multiple-spike" neurons have oval or fusiform somata with four
      or five thick primary dendritic trunks that leave the soma in opposite
      directions; they have spiny secondary and tertiary dendrites. Finally, neurons
      which discharge with a "single spike" to depolarizing pulses are round with four
      or five densely spiny dendrites, affording these neurons a mossy appearance. The
      results indicate that most of the amygdaloid neurons respond to carbachol with a
      depolarization. This effect was concomitant with either decrease or no change in
      the membrane input resistance and was not blocked by the addition of Ba2+, an M
      current blocker, indicating that a conductance pathway other than K+ is involved
      in the response to carbachol.

PMID- 9153655
TI  - Tachykinin neurokinin-1 and neurokinin-3 receptor-mediated responses in guinea
      pig substantia nigra: an in vitro electrophysiological study.
AB  - The effects of tachykinin receptor agonists and antagonists were investigated
      using intra- and extracellular recordings on spontaneously firing nigral neurons
      in guinea-pig brain slices. In 70 of 76 electrophysiologically identified
      dopaminergic neurons, a concentration-dependent increase in firing rate was
      induced by the selective neurokinin-3 tachykinin agonist senktide and by the
      natural tachykinin agonists neurokinin B and substance P, with EC50 values of
      14.7, 31.2 and 12200 nM respectively. These responses were inhibited in a
      concentration- and time-dependent manner by the selective non-peptide neurokinin
      3 receptor antagonist SR 142801 (1-100 nM; n=23), but neither by its S-enantiomer
      SR 142806 (100 nM; n=4) nor by selective antagonists of neurokinin-1 (SR 140333)
      or neurokinin-2 (SR 48968) receptors (both at 100 nM; n=3). The selective
      neurokinin-1 agonist [Sar9,Met(O2)11]substance P (30-100 nM; n=23) and the
      selective neurokinin-2 agonist [Nle10]neurokinin A(4-10)(30-100 nM; n=13) were
      without any effect on dopaminergic cells. In 13 of 21 electrophysiologically
      identified, presumably GABAergic neurons located in the pars compacta of the
      substantia nigra, excitatory responses were evoked concentration dependently by
      substance P and [Sar9,Met(O2)11]substance P, with EC50 values of 18.6 and 41.9 nM
      respectively. These responses were inhibited by SR 140333 (100 nM; n=3), but
      neither by its R-enantiomer SR 140603 nor by SR 142801 (both at 100 nM; n=3).
      Senktide and [Nle10]neurokinin A(4-10) (both at 30-100 nM; n=10) were without
      effect on these presumed GABAergic neurons. A small population (12%) of pars
      compacta neurons was insensitive to any of the three selective tachykinin
      agonists. In the nigral pars reticulata, 12 neurons were recorded which had an
      electrophysiological profile similar to that of presumed GABAergic neurons in the
      pars compacta. Of these 12 cells, seven did not respond to any of the selective
      tachykinin agonists tested, while five were excited by senktide in a
      concentration-dependent manner (EC50=98.5 nM). Although this value was
      significantly higher than that found for dopaminergic neurons in the pars
      compacta, senktide-evoked responses were inhibited by SR 142801 (100 nM; n=3). We
      conclude that, in the guinea-pig substantia nigra, tachykinins evoke excitatory
      responses in both dopaminergic and non-dopaminergic neurons; however, the
      sensitivity to tachykinin agonists (neurokinin-1 versus neurokinin-3) depends on
      both neuronal type and localization.

PMID- 9153656
TI  - Dopamine and GABA receptors in cultured substantia nigra neurons: correlation of
      electrophysiology and immunocytochemistry.
AB  - Primary neuron cultures were made separately from the substantia nigra pars
      compacta and the substantia nigra pars reticulata of neonatal rats. Using the
      whole-cell patch-clamp, we tested for the presence of dopamine and GABA receptor
      subtypes by applying dopamine receptor agonists [the D2 receptor agonist
      quinpirole and the D1 receptor agonist R(+)-SKF-38393] and GABA receptor agonists
      (GABA and baclofen). The D2 agonists and the GABA(B) agonist increased an inward
      rectifier K+ conductance, while the D1 agonist decreased this K+ conductance.
      Application of GABA increased membrane conductance, probably by increasing Cl-
      permeability through GABA(A) receptors. Following the physiological tests, the
      same neuron was examined by double immunocytochemical labeling for antibody to
      tyrosine hydroxylase and antibody to GABA. Neurons which responded to the D2
      agonist were dopaminergic neurons, while neurons which did not respond to D2
      agonist were mostly GABAergic or non-dopaminergic/non-GABAergic. Neurons which
      responded to the D1 agonist were non-dopaminergic/non-GABAergic. GABA(A)
      receptors were present in all types of neurons, while GABA(B) receptors were
      located on some dopaminergic neurons and some GABAergic neurons. These results
      largely agree with the published data on in vivo or brain slice preparations,
      indicating that these neurons of neonatal rat brains, after being dissociated,
      produce the same transmitters and the same receptors in culture as those in vivo.

PMID- 9153657
TI  - Ionic mechanisms involved in the spontaneous firing of tegmental pedunculopontine
      nucleus neurons of the rat.
AB  - We have previously defined three types of tegmental pedunculopontine nuclei
      neurons based on their electrophysiological characteristics: Type I neurons
      characterized by low-threshold Ca2+ spikes, Type II neurons which displayed a
      transient outward current (A-current), and Type III neurons having neither low
      threshold spikes nor A-current [Kang Y. and Kitai S. T. (1990) Brain Res. 535, 79
      95]. In this report, ionic mechanisms underlying repetitive firing of Type I
      (n=15) and Type II (n=69) neurons were studied in in vitro slice preparations.
      Type I neurons did not fire rhythmically but their spontaneous firing frequency
      ranged from 0 to 19.5 spikes/s (mean 9.7 spikes/s). The spontaneous firing of
      Type II neurons was rhythmic, with a mean frequency of 9.6 spikes/s (range 3.5
      16.0 spikes/s). Choline acetyltransferase immunohistochemistry combined with
      biocytin labeling indicated that none of the Type I neurons were immunopositive
      to choline acetyltransferase, while 60% (42 of 69) of Type II neurons were
      immunopositive. There was no apparent difference in the electrophysiological
      membrane properties of immunopositive and immunonegative Type II neurons. At
      membrane potentials subthreshold for Na+ spikes (-50 mV), spontaneous membrane
      oscillations (11.6 Hz) were observed: these underlie the spontaneous repetitive
      firing of Type I neurons. The subthreshold membrane oscillation was tetrodotoxin
      sensitive but was not affected by Ca2+-free medium. A similar tetrodotoxin
      sensitive subthreshold membrane oscillation (10.5 Hz) was also observed in Type
      II neurons. However, in Type II neurons a membrane oscillation was also observed
      at higher membrane potentials (-50 mV). This high-threshold oscillation was
      insensitive to tetrodotoxin and Na+-free medium, but was eliminated in Ca2+-free
      conditions. The amplitude and frequency of the high-threshold oscillation was
      increased upon membrane depolarization. At the most prominent oscillatory level
      (around -40 mV), the high-threshold oscillation had a mean frequency of 8.8 Hz.
      The high-threshold Ca2+ spike was triggered from the peak potential (-35 to 
      30mV) of the high-threshold oscillation. Application of tetraethylammonium
      chloride (< 5 mM) increased the amplitude of the high-threshold oscillation,
      while nifedipine greatly attenuated the high-threshold oscillation without
      changing the shape of the high-threshold Ca2+ spike. Application of Cd2+
      eliminated both the high-threshold oscillation and the high-threshold Ca2+ spike,
      and omega-conotoxin reduced the size of the high-threshold Ca2+ spike without
      affecting the frequency of the high-threshold oscillation. Nickel did not have
      any effect on either the high-threshold oscillation or the high-threshold Ca2+
      spike. These data suggest an involvement of N- and L-type Ca2+ channels in the
      generation of the high-threshold oscillation and the high-threshold Ca2+ spike,
      respectively. The results indicate that a persistent Na+ conductance plays a
      crucial role in the subthreshold membrane oscillation, which underlies
      spontaneous repetitive firing in Type I neurons. On the other hand, in addition
      to a persistent Na+ conductance for subthreshold membrane oscillation, a voltage
      dependent Ca2+ conductance with Ca2+-dependent K+ conductance (for the high
      threshold oscillation) may be responsible for rhythmic firing of Type II neurons.

PMID- 9153658
TI  - GABA release in the locus coeruleus as a function of sleep/wake state.
AB  - GABA, glutamate, and glycine release in the locus coeruleus were measured as a
      function of sleep/wake state in the freely-behaving cat using the microdialysis
      technique. GABA release was found to increase during rapid-eye-movement sleep as
      compared to waking values. GABA release during slow-wave sleep was intermediate
      between that of waking states and rapid-eye-movement sleep. The concentration of
      glutamate and glycine in microdialysis samples was unchanged across sleep and
      wake states. Our findings are consistent with the hypothesis that GABAergic
      inhibition is responsible for the cessation of discharge in locus coeruleus
      neurons during REM sleep. The data suggest that a population of GABAergic neurons
      innervating the locus coeruleus are selectively active during rapid-eye-movement
      sleep.

PMID- 9153659
TI  - Increased potency of neuropeptide Y to antagonize alpha2-adrenoceptor function in
      the nucleus tractus solitarii of the spontaneously hypertensive rat.
AB  - The regulation by neuropeptide Y of alpha2-adrenoceptors in the nucleus tractus
      solitarii was evaluated in the adult normotensive Wistar Kyoto rat and the adult
      spontaneously hypertensive rat. The microinjection of a submaximal dose of l
      noradrenaline (800 pmol in 50 nl) alone into the nucleus tractus solitarii
      produced a significant reduction in the mean arterial blood pressure in either
      strain. The threshold dose (1 pmol in 50 nl) of neuropeptide Y(1-36) for the
      vasodepressor response in the Wistar Kyoto rat was five times higher than that
      (0.2 pmol in 50 nl) in the spontaneously hypertensive rat. Furthermore,
      neuropeptide Y(1-36) at 0.2 pmol in 50 nl could significantly counteract the
      vasodepressor response to l-noradrenaline (800 pmol in 50 nl) in the
      spontaneously hypertensive rat, but not in the Wistar Kyoto rat, in which 1 pmol
      in 50 nl of neuropeptide Y(1-36) must be employed to counteract the vasodepressor
      response to l-noradrenaline (800 pmol in 50 nl), although the vasodepressor
      responses are of a similar magnitude. The in situ hybridization and quantitative
      receptor autoradiographical experiments showed that the alpha2A-adrenoceptor
      messenger RNA levels and the B(max) value of the alpha2-adrenoceptor agonist
      [3H]p-aminoclonidine binding sites measured in the nucleus tractus solitarii of
      the spontaneously hypertensive rat were substantially lower than those in the
      Wistar Kyoto rat. The quantitative receptor autoradiographical results were
      consistent with the cardiovascular results and showed that in the spontaneously
      hypertensive rat, neuropeptide Y(1-36) at 1 nM led to a significant increase in
      the K(d) value of [3H]p-aminoclonidine binding sites. In the Wistar Kyoto rat,
      neuropeptide Y(1-36) produced this effect only at 10 nM. The present study
      provides evidence for an increase of the potency of neuropeptide Y(1-36) to
      antagonistically modulate alpha2-adrenoceptors in the nucleus tractus solitarii
      of the spontaneously hypertensive rat. This enhanced antagonistic action may
      partly be related to a reduction in the number of alpha2A-adrenoceptors in the
      nucleus tractus solitarii of the spontaneously hypertensive rat, since a decrease
      has been observed in the alpha2A-adrenoceptor messenger RNA levels and the alpha2
      adrenoceptor binding sites in the spontaneously hypertensive rat. This increased
      potency of neuropeptide Y(1-36) to antagonize alpha2-adrenoceptor function in the
      nucleus tractus solitarii of the spontaneously hypertensive rat may contribute to
      the development of high blood pressure in this hypertensive strain.

PMID- 9153660
TI  - Synaptic excitation in the dorsal nucleus of the lateral lemniscus: whole-cell
      patch-clamp recordings from rat brain slice.
AB  - The synaptic events underlying the excitation of neurons in the rat's dorsal
      nucleus of the lateral lemniscus were studied by whole-cell patch-clamp
      recordings in a brain slice preparation of the auditory midbrain. Both current
      clamp and voltage-clamp data were obtained with the brain slice submerged in
      artificial cerebrospinal fluid. The rats were between 21 and 35 days of age at
      the time the recordings were made. Synaptic responses were evoked by a bipolar
      stimulating electrode placed on the lateral lemniscus just ventral to the dorsal
      nucleus. To eliminate glycinergic inhibitory responses, all physiological data
      were gathered with 0.5 microM strychnine added to the saline bath. Under current
      clamp conditions, excitatory postsynaptic potentials could be subdivided into
      early and late components. The early component produced a single, highly
      reliable, short-latency spike and the later component produced a more variable,
      long-latency spike or train of spikes. The non-N-methyl-D-aspartate antagonist, 6
      cyano-7-nitroquinoxaline-2,3-dione, completely blocked the early excitatory
      postsynaptic potential and its associated action potential. The N-methyl-D
      aspartate antagonist, D,L-2-amino-5-phosphonovaleric acid, blocked the later
      excitatory postsynaptic potential and its action potentials. Typically, both
      early and late excitatory postsynaptic potentials could be recorded from the same
      cell, but the early excitatory postsynaptic potential was evoked at lower
      stimulus levels and had a larger amplitude than the later excitatory postsynaptic
      potential. Under voltage-clamp conditions, dorsal nucleus of the lateral
      lemniscus neurons responded to stimulation of the lateral lemniscus with
      excitatory postsynaptic currents. Outward excitatory postsynaptic currents were
      recorded with holding potentials that depolarized the cell membrane and inward
      currents were seen when the cell was hyperpolarized. The current-voltage (I-V)
      relation of the early peak portion of the excitatory postsynaptic current was
      nearly linear, whereas the I-V relation of the later excitatory postsynaptic
      current (12 ms after the peak) was non-linear over the range between -50 and -
      100 mV. The outward excitatory postsynaptic current consisted of an early current
      that was selectively blocked by 6-cyano-7-nitroquinoxaline-2,3-dione and a later
      current that was blocked by D,L-2-amino-5-phosphonovaleric acid. In artificial
      cerebrospinal fluid with normal concentrations of Mg2+, the inward excitatory
      postsynaptic current was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione, but was
      not affected by D,L-2-amino-5-phosphonovaleric acid. In Mg2+-free artificial
      cerebrospinal fluid. however, the early component of the inward excitatory
      postsynaptic current was selectively blocked by 6-cyano-7-nitroquinoxaline-2,3
      dione and a later component was blocked by D,L-2-amino-5-phosphonovaleric acid.
      The results indicate that both N-methyl-D-aspartate and non-N-methyl-D-aspartate
      receptor-mediated synaptic responses are present in dorsal nucleus of the lateral
      lemniscus neurons of rats at 21-35 days of age. The N-methyl-D-aspartate
      component had a longer time-course and a higher threshold than the non-N-methyl-D
      aspartate component, and was subject to a voltage-dependent Mg2+ block when the
      cell's membrane was hyperpolarized. The long-duration N-methyl-D-aspartate
      component is probably responsible for the prolonged inhibitory effect of dorsal
      nucleus of the lateral lemniscus neurons on physiological responses in the rat's
      inferior colliculus.

PMID- 9153661
TI  - Catecholamine enzymes and neuropeptides are expressed in fibres and somata in the
      intermediate gray matter in chronic spinal rats.
AB  - Spinal cord injury disrupts control of sympathetic preganglionic neurons because
      bulbospinal input has been lost and the remaining regulation is accomplished by
      spinal circuits consisting of dorsal root afferent and spinal neurons. Moreover,
      an initial retraction and regrowth of dendrites of preganglionic neurons in
      response to deafferentation creates the potential for remodelling of spinal
      circuits that control them. Although catecholamines and neuropeptide Y are found
      in descending inputs to the preganglionic neurons, their presence in spinal
      circuits has not been established. Spinal circuits controlling preganglionic
      neurons contain substance P but participation of these peptidergic neurons in
      remodelling responses has not been examined. Therefore, we compared
      immunoreactivity for the catecholamine-synthesizing enzyme dopamine beta
      hydroxylase, for neuropeptide Y and for substance P in the intermediate gray
      matter of the spinal cord in control rats and in rats seven or fourteen days
      after transection at the fourth thoracic cord segment. Sympathetic preganglionic
      neurons were retrogradely labelled by intraperitoneal injection of the tracer
      FluoroGold. These experiments yielded three original findings. 1) At one and two
      weeks after cord transection, fibres and terminals immunoreactive for dopamine
      beta-hydroxylase and neuropeptide Y were consistently found in the
      intermediolateral cell column in segments caudal to the transection. The area of
      fibres and terminals containing these immunoreactivities was markedly reduced
      compared to control rats or to segments rostral to the transection in the spinal
      rats. 2) Immunoreactivity for substance P was increased after cord transection
      and the distribution of fibres immunoreactive for this peptide in segments caudal
      to the transection extended more widely through the intermediate gray matter.
      These reactions demonstrated a plastic reaction to cord transection by spinal
      neurons expressing substance P. 3) Dopamine beta-hydroxylase expression was up
      regulated in somata within the intermediate gray matter of spinal segments caudal
      to the transection. The numbers of somata immunoreactive for this enzyme
      increased six-fold by 14 days after cord transection, compared to the few somata
      counted in control rats. In conclusion, the presence of a catecholamine
      synthesizing enzyme and neuropeptides in fibres surrounding sympathetic
      preganglionic neurons caudal to a cord transection suggests a source of
      catecholamines and these peptides within spinal circuits in the chronic spinal
      rat. The presence of dopamine beta-hydroxylase in a markedly greater number of
      neuronal somata after cord transection reflects significant up-regulation of gene
      expression and may indicate a switch by these neurons to an adrenergic phenotype,
      revealing a plastic response to injury within the spinal cord.

PMID- 9153662
TI  - The potential role of spinal cord cyclooxygenase-2 in the development of Freund's
      complete adjuvant-induced changes in hyperalgesia and allodynia.
AB  - Chronic inflammatory conditions produce a state of hyperalgesia which is evident
      from a few hours to days after administration of an inflammatory stimulus. The
      molecular mechanisms involved in the initiation of hyperalgesia are not well
      understood and in this study we have investigated the role of prostaglandins in
      this process in the rat. Unilateral intraplantar injection of Freund's complete
      adjuvant produces an immediate localized swelling (oedema) with the development
      of altered pain responses in the ipsilateral paw such as a reduced threshold to
      noxious stimuli (hyperalgesia) and lowered thresholds such that normally
      innocuous stimuli produce a pain response (allodynia). We have monitored levels
      of cyclooxygenase messenger RNA and prostaglandins in lumbar spinal cord in
      parallel with these behavioural responses (oedema, hyperalgesia and allodynia)
      and identified a marked increase in cyclooxygenase-2 messenger RNA (3-fold),
      maximal at 2-4 h after Freund's complete adjuvant, followed by a significant
      increase in 6-keto prostaglandin F1alpha and prostaglandin E2 which is maximal by
      8 h. Pretreatment of animals with the unselective cyclooxygenase inhibitor
      indomethacin attenuated oedema (approximately 40%) and allodynia (80-100%), but
      had no effect on the development of mechanical hyperalgesia. Pretreatment with
      the cyclooxygenase-2 selective inhibitors DuP 697, flosulide and SC58125 also
      attenuated allodynia (by 80-100%) but had no effect on the development of oedema
      or mechanical hyperalgesia. The marked increase in cyclooxygenase-2 messenger RNA
      in the lumbar spinal cord following intraplantar Freund's complete adjuvant
      suggests that the cyclooxygenase enzyme and its product may have a role in the
      adaptive response that occurs in the lumbar spinal cord during a peripheral
      inflammatory reaction. Pharmacological analysis reveals that prostaglandins are
      directly involved in the development of allodynia. However, these studies show
      that the development of mechanical hyperalgesia does not require the production
      of prostaglandins indicating that more than one pathway mediates the altered pain
      responses associated with a peripheral inflammatory lesion.

PMID- 9153663
TI  - Ligand-induced down-regulation of Trk messenger RNA, protein and tyrosine
      phosphorylation in rat cortical neurons.
AB  - Chronic exposure of brain neurons to nerve growth factor in vitro and in vivo
      results in increased levels of the nerve growth factor receptor TrkA. In
      contrast, in the present study, we have found that chronic exposure of rat
      embryonic cortical neurons to brain-derived neurotrophic factor (BDNF) leads to a
      pronounced reduction of the levels of protein and messenger RNA for the full
      length but not the truncated BDNF receptor TrkB. Similar effects were observed
      with the other TrkB ligands neurotrophin-3 and neurotrophin-4/5. After
      pretreatment with BDNF, neurotrophin-3 or neurotrophin-4/5, subsequent tyrosine
      phosphorylation responses of the remaining Trks to the same factors were greatly
      reduced. Three days exposure of rat embryonic cortical neurons to BDNF induced an
      absolute refractory period of several hours, with no subsequent response to the
      same factor. Similar but less pronounced refractory effects were observed with
      neurotrophin-3 and neurotrophin-4/5. Our results suggest a negative regulatory
      effect of BDNF and other TrkB ligands on TrkB receptors. Down-regulation of the
      TrkB response by its ligands might play a role in the control of BDNF action
      during early development, when BDNF levels significantly increase. Our findings
      are also of potential clinical relevance, since the possibility of ligand-induced
      down-regulation of the receptor response needs to be addressed when considering
      BDNF or other neurotrophins for the therapy of neurodegeneration.

PMID- 9153665
TI  - Anabolic-androgenic steroid induced alterations in choline acetyltransferase
      messenger RNA levels of spinal cord motoneurons in the male rat.
AB  - The effect of chronic supraphysiological doses of anabolic-androgenic steroids,
      such as those illegally used by recreational, amateur and professional athletes
      to increase muscle mass and strength, on motoneurons has not been established.
      The choline acetyltransferase activity levels of perineal muscles in the male rat
      are modulated by plasma testosterone levels. These muscles are innervated by the
      sexually dimorphic motoneurons of the spinal nucleus of the bulbocavernosus.
      Since the primary source of choline acetyltransferase in muscle is motoneuronal,
      testosterone may modulate perineal muscle choline acetyltransferase activity by
      regulating choline acetyltransferase messenger RNA levels in motoneurons. The
      purpose of this study was to determine if choline acetyltransferase messenger RNA
      levels in cervical and lumbar spinal motoneurons are affected by chronic (four
      weeks) changes of plasma testosterone levels in the adult male rat. Using in situ
      hybridization, choline acetyltransferase messenger RNA levels were analysed in
      four motor columns: the spinal nucleus of the bulbocavernosus, the retrodorsal
      lateral nucleus of the lumbar spinal cord, and the lateral motor columns of the
      cervical and lumbar spinal cords. Chronic exposure to supraphysiological levels
      of testosterone (five- to ten-times physiologic levels) significantly increased
      choline acetyltransferase messenger RNA in all four motor columns. Subsequent to
      castration, choline acetyltransferase messenger RNA levels decreased in
      motoneurons of the spinal nucleus of the bulbocavernosus and the retrodorsal
      lateral nucleus. This observation suggests that the decrease in choline
      acetyltransferase activity levels of muscles innervated by spinal nucleus of the
      bulbocavernosus motoneurons may be due to changes in choline acetyltransferase
      protein levels. Indeed, testosterone replacement therapy of castrated males
      prevented the decline of choline acetyltransferase messenger RNA levels in
      motoneurons. The results of this study demonstrate that anabolic-androgenic
      steroids can affect the levels of specific messenger RNAs in motoneuron
      populations throughout the spinal cord suggesting that motoneuronal
      characteristics are modulated by circulating anabolic-androgenic steroid levels
      regardless of the purported "androgen sensitivity" of the specific neuromuscular
      system.

PMID- 9153664
TI  - Effects of nerve growth factor, brain-derived neurotrophic factor and
      neurotrophin-3 on the laminar distribution of transganglionically fransported
      choleragenoid in the spinal cord dorsal horn following transection of the sciatic
      nerve in the adult rat.
AB  - Spinal cord projections from transected sciatic nerves treated with different
      neurotrophins were investigated in the adult rat following injections of
      choleragenoid into the proximal stump of the injured nerve. Transganglionically
      transported choleragenoid labelled primary afferent fibres in all spinal cord
      dorsal horn laminae except the outer part of lamina II (II(o)), which is almost
      devoid of labelling. Transection of the sciatic nerve, however, resulted in
      intense transganglionic choleragenoid labelling in lamina II(o) and in lamina I.
      In this study, the sciatic nerve was transected bilaterally and 4erve growth
      factor (6 or 24 microg), brain-derived neurotrophic factor (20 microg),
      neurotrophin-3 (27 microg) or cytochrome C (8 microg; control substance) was
      applied unilaterally during postoperative survival times of eight, 16 and 32
      days. The animals received bilateral injections of choleragenoid into the injured
      nerve two days before they were killed. The effect of the axotomy and
      neurotrophin treatment was evaluated by analysing the extent of choleragenoid and
      substance P immunoreactivity in the somatotopically appropriate spinal cord
      dorsal horn regions. At eight days' postoperative survival, laminae I and II(o)
      on the transected, non-treated side showed much more intense choleragenoid-like
      immunoreactivity compared to the contralateral transected, nerve growth factor
      treated (6 and 24 microg) side. A similar situation was also found in cases
      treated with the higher dose (24 microg) at 16 days but to a lesser degree when
      the lower (6 microg) dose was used. After 32 days' survival, there was no
      detectable side difference in the choleragenoid labelling pattern. At 16 days'
      survival, the mean area of choleragenoid-positive ganglion cell body profiles in
      the L5 dorsal root ganglion of the transected, non-treated side was significantly
      smaller than the mean area of the transected, nerve growth factor-treated (24
      microg) neurons. An axotomy-induced depletion of substance P-like
      immunoreactivity was seen from eight days' survival and onwards, whereas on the
      nerve growth factor-treated side a clearcut substance P depletion was not
      observed until 32 days. Brain-derived neurotrophic factor, neurotrophin-3 and
      cytochrome C had no detectable effects on the distribution of choleragenoid
      labelling or substance P-like immunoreactivity in the dorsal horn following
      sciatic nerve transection. In conclusion, peripheral nerve injury-induced
      expansion of primary afferent choleragenoid labelling in the spinal cord dorsal
      horn is counteracted by treating the axotomized nerve with nerve growth factor.

PMID- 9153666
TI  - Sodium-dependent increase in quantal secretion induced by brevetoxin-3 in Ca2+
      free medium is associated with depletion of synaptic vesicles and swelling of
      motor nerve terminals in situ.
AB  - Brevetoxin-3 at nanomolar concentrations markedly enhanced spontaneous quantal
      transmitter release from neuromuscular junctions equilibrated in a Ca2+-free EGTA
      medium. After about 3 h, the sustained increase in miniature endplate potential
      frequency led to an exhaustion of transmitter release. This increase still
      occurred after loading the nerve terminals with the Ca2+ chelator bis
      (aminophenoxy)ethanetetra-acetate or after pretreatment with various
      pharmacological agents known to prevent Ca2+ release from intracellular pools,
      but was completely prevented by the Na+ channel blocker tetrodotoxin. Brevetoxin
      3 also increased miniature endplate potential frequency from junctions treated
      with botulinum type-A toxin, but to a smaller extent than at normal junctions. At
      normal junctions, brevetoxin-3 exposure for 2 h increased the three-dimensional
      projected area of living motor nerve terminals in situ by about 74% while at
      botulinum type-A poisoned junctions a similar toxin exposure caused only a 29%
      increase. Tetrodotoxin prevented such effects, indicating that they are related
      to both Na+ entry into the terminals and increased quantal transmitter release.
      Ultrastructural examination of nerve terminals from junctions exposed for 3 h to
      brevetoxin-3 revealed profound depletions of clear and large dense core synaptic
      vesicles and an increase in coated vesicles and axolemma infoldings. These
      results indicate that brevetoxin-3 impairs the recycling of clear synaptic
      vesicles and are consistent with our immunofluorescent observations showing that
      synaptophysin epitopes can be revealed without nerve terminal permeabilization.
      In contrast, no such changes were detected in nerve terminals poisoned with
      botulinum type-A toxin which, after 3 h exposure to brevetoxin-3, retained their
      synaptic vesicles and had a normal appearance. We conclude that tetrodotoxin
      sensitive Na+ entry into motor nerve terminals induced by brevetoxin-3 triggers
      external Ca2+-independent asynchronous quantal transmitter release, blocks
      synaptic vesicle recycling and induces swelling of the terminals. We suggest that
      an excess of cytoplasmic Na+ per se can activate the asynchronous
      neurotransmitter release process.

PMID- 9153667
TI  - Absence of nerve-dependent conversion of rapidly degrading to stable
      acetylcholine receptors at adult innervated endplates.
AB  - It has been suggested that acetylcholine receptors newly inserted into adult
      innervated endplates have a rapid degradation rate, but are normally converted to
      a stable, slowly degrading form in a nerve-dependent fashion. Denervation
      therefore should eliminate conversion and cause pre-existing unconverted
      receptors to continue degrading rapidly. We tested this model of nerve-dependent
      conversion in mouse sternomastoid muscle, using quantitative electron microscopic
      autoradiography in order to specifically examine degradation of receptors at
      identified endplate membrane. Prior to denervation, we labelled the receptors
      with sequential alpha-bungarotoxin exposures, using conditions designed to
      maximize the predicted effect of denervation. However, we observed no difference
      in the rate of receptor degradation at innervated and denervated endplates up to
      seven days after denervation (at which time accelerated degradation of pre
      existing stabilized receptors is known to begin in this muscle). The regulation
      of endplate acetylcholine receptor metabolic turnover is a complex and still
      largely undefined issue, related to many factors such as subunit composition,
      cytoskeleton and basement membrane composition, muscle activity, and neural
      influences. In particular, the nerve's influence on the normal stabilization of
      receptors at innervated adult endplates has been controversial. Our data indicate
      that slow degradation is probably an inherent property of newly inserted
      junctional receptors, and argue against nerve-dependent conversion and
      stabilization. Based on the present data, however, we cannot rule out the
      presence of a small nerve-independent subpopulation that degrades rapidly. The
      molecular mechanisms involved in establishing and maintaining a stable population
      of adult endplate acetylcholine receptors remain to be established.

PMID- 9153668
TI  - Enhanced tolerance of neuroblastoma cells towards the neurotoxin 6
      hydroxydopamine following specific cell-cell interaction with primary astrocytes.
AB  - Dopamine neuroblastoma (SH-SY5Y) cells exhibit a high affinity of adhesion for
      primary astroglial cells. The homophilic aggregation of SH-SY5Y cells is greatly
      reduced and the neuroprocesses are enhanced when co-cultured with the astrocytes.
      However, such affinity was not detected in the mouse when these cells were co
      cultured with fibroblast and endothelial cells. SH-SY5Y cells in monoculture are
      very sensitive towards the neurotoxin 6-hydroxydopamine, but this sensitivity is
      substantially reduced in co-culture with astrocytes. The acquired cytoprotection
      of the neuroblastoma cells in co-culture against 6-hydroxydopamine is time
      dependent following adhesion with the astrocytes. There is no evidence to
      indicate that the increase in survival of the SH-SY5Y cells against 6
      hydroxydopamine is due to inactivation of 6-hydroxydopamine induced by the
      extracellular factors secreted from the astrocytes, neither is there any
      indication suggesting the removal of 6-hydroxydopamine by an astrocyte uptake
      mechanism. The release of trophic factors by the astrocytes does not seem to play
      a role in the protection of the neuroblastoma cells against 6-hydroxydopamine.
      The neuroblastoma cells became susceptible to 6-hydroxydopamine in the astrocyte
      co-cultures when they were physically separated from the astroglial cells by
      trans-well inserts. Neither non-selective adhesions, such as adhesion with
      denatured astrocytes or with other types of cells (i.e. endothelial or fibroblast
      cells), nor adhesion enhanced by chemical agents can increase the cytoprotection
      of SH-SY5Y against 6-hydroxydopamine. These results suggest that the increase in
      survival of neuroblastoma cells against 6-hydroxydopamine in the astrocyte co
      cultures is probably a result of specific cell-cell adhesion and the subsequent
      interactions.

PMID- 9153669
TI  - Fos immunohistochemical determination of brainstem neuronal activation in the
      muskrat after nasal stimulation.
AB  - Stimulation of the nasal passages of muskrats with either ammonia vapours or
      retrogradely-flowing water produced cardiorespiratory responses (an immediate 62%
      decrease in heart rate, 29% increase in mean arterial blood pressure, and
      sustained expiratory apnoea). We used the immunohistological detection of Fos,
      the protein product of the c-fos gene, as a marker of neuronal activation to help
      elucidate the brainstem circuitry of this cardiorespiratory response. After
      repeated ammonia stimulation of the nasal passages, increased Fos expression was
      detected within the spinal trigeminal nucleus (ventral laminae I and II of the
      medullary dorsal horn, ventral paratrigeminal nucleus, and spinal trigeminal
      nucleus interpolaris), an area just ventromedial to the medullary dorsal horn,
      the caudal dorsal reticular formation and the area of the A5 catecholamine group
      compared to control animals. Repeated water stimulation of the nasal passages
      produced increased Fos expression only in the A5 catecholamine group. There was
      an increase in the number of Fos-positive cells in the ammonia group in the
      ventral laminae I and II of the medullary dorsal horn and the ventral
      paratrigeminal nuclei compared with the water group. We conclude that ammonia
      stimulation of the nasal passages produces a different pattern of neuronal
      activation within the brainstem compared with water stimulation. We also conclude
      that Fos immunohistochemistry is a good technique to determine functional
      afferent somatotopy, but that immunohistochemical detection of Fos is not a good
      technique to identify the medullary neurons responsible for the efferent aspects
      of an intermittently produced cardiorespiratory reflex.

PMID- 9153670
TI  - Ill fitting genes: the biology of weight and shape control in relation to body
      composition and eating disorders.

PMID- 9153671
TI  - Can dieting cause an eating disorder?

PMID- 9153672
TI  - Life events and the onset of bulimia nervosa: a controlled study.
AB  - BACKGROUND: Life events may play a role in precipitating the onset of bulimia
      nervosa. This study aimed to determine the rates of occurrence of certain life
      events during the year before onset of disordered eating in women with bulimia
      nervosa, and to compare them with the rates among age-matched normal controls.
      METHODS: The subjects were 102 women with bulimia nervosa and 204 women without
      an eating disorder, all recruited from the same community sample of young adult
      women. Interview measures were used for diagnosis and for assessment of life
      events. RESULTS: The bulimia nervosa cases reported more life events during the
      year before onset of disordered eating than were reported by controls of the same
      age. Events involving disruption of family or social relationships, or a threat
      to physical safety, were especially common among the bulimia nervosa cases.
      CONCLUSIONS: These findings suggest that certain life events may play a role in
      precipitating the onset of bulimia nervosa. The study was retrospective in
      design. Prospective studies of the role of life events would be valuable, but
      difficult to perform.

PMID- 9153673
TI  - Is there a specific trauma precipitating anorexia nervosa?
AB  - BACKGROUND: The aims of this study were to explore the role of life events and
      difficulties in the onset of anorexia nervosa and bulimia nervosa and to find out
      whether events and difficulties with a specific meaning, i.e. those of a certain
      sexual nature, are important in the onset of anorexia nervosa. METHODS: Seventy
      two patients with anorexia nervosa (AN) and 29 with bulimia nervosa (BN) were
      assessed with the life events and difficulties schedule (Brown & Harris, 1978),
      the year before onset was studied. A new dimension to measure specific meaning of
      life events and difficulties called 'pudicity' was developed. Subjects from two
      community cohorts were used as comparison groups (Brown & Harris, 1978; Andrews
      et al. 1990). RESULTS: Anorexic patients, bulimic patients and community controls
      did not differ in proportion of patients with at least one severe event; however,
      significantly more AN and BN patients than community controls had experienced a
      major difficulty. Sixty-seven per cent of anorexics and 76% of bulimia nervosa
      patients had either a severe event or a marked difficulty during the year before
      onset. In AN and BN the most common serious life stresses before onset concerned
      close relationships with family and friends with BN patients being significantly
      more often than AN patients directly involved in the problem (interpersonal
      events). Patients with anorexia nervosa had significantly more pudicity events
      before onset than BN patients or community controls. CONCLUSION: While serious
      life stresses commonly precede the onset of anorexia nervosa and bulimia nervosa,
      problems with sexuality seem to be specific in triggering the onset of anorexia
      nervosa.

PMID- 9153674
TI  - Setting the scene for eating disorders, II. Childhood helplessness and mastery.
AB  - BACKGROUND: Previous studies have examined childhood factors that appear to
      increase the risk of developing an eating disorder (e.g. sexual abuse and
      parental care). Studies have not yet examined whether the way in which women cope
      with these adversities in childhood influences the risk. METHOD: Using a semi
      structured interview, childhood helplessness and mastery were measured (based on
      behavioural indices) in women with and without a history of eating disorders.
      RESULTS: There was a higher rate of childhood helplessness and a lower rate of
      childhood mastery in women with eating disorders compared to those without.
      Furthermore, this difference did not appear to be a result of current psychiatric
      state. CONCLUSION: It is concluded that it is not simply the presence of
      adversity in childhood which is of aetiological importance in the development of
      eating disorders but the way in which these are negotiated.

PMID- 9153675
TI  - Stressful life events and genetic liability to major depression: genetic control
      of exposure to the environment?
AB  - BACKGROUND: Although overwhelming evidence suggests that genetic and
      environmental risk factors both contribute to the aetiology of major depression
      (MD), we know little of how these two risk factor domains inter-relate. In
      particular, can the genetic liability to MD increase the risk of experiencing
      stressful life events (SLEs)? METHODS: Using discrete time survival analysis in a
      population-based sample of 2164 female twins, we examined whether the risks for
      nine personal and three aggregate network SLEs were predicted by the level of
      genetic liability to MD, indexed by the lifetime history of MD in monozygotic and
      dizygotic co-twins. RESULTS: Genetic liability to MD was associated with a
      significantly increased risk for six personal SLEs (assault, serious marital
      problems, divorce/breakup, job loss, serious illness and major financial
      problems) and one network SLE (trouble getting along with relatives/friends).
      This effect was not due to SLEs occurring during depressive episodes. Similar
      results were found using structural equation twin modelling. In contrast to the
      pattern observed with MD, the genetic liability to alcoholism impacted on the
      risk for being robbed and having trouble with the law. CONCLUSION: In women,
      genetic risk factors for MD increase the probability of experiencing SLEs in the
      interpersonal and occupational/financial domains. Genes can probably impact on
      the risk for psychiatric illness by causing individuals to select themselves into
      high risk environments.

PMID- 9153676
TI  - The determinants of parenting: an epidemiological, multi-informant, retrospective
      study.
AB  - BACKGROUND: To understand the relationship between parenting and psychopathology
      in offspring, it is critical to clarify the determinants of parenting behaviour
      itself. METHODS: A 16-item version of the Parental Bonding Instrument (PBI) was
      administered to parents of epidemiologically sampled adult female-female twin
      pairs, who reported on the parenting they provided to their twins, and to the
      twins themselves who reported on the parenting they and their co-twin had
      received (N = 828 twin families). Using a mixed-model regression, we examined the
      impact on parenting, as retrospectively reported by parents and twins, of six
      variable domains: demographic factors, family characteristics, parental symptoms
      and personality, parental psychopathology, child vulnerability and childhood
      temperament. RESULTS: The PBI yielded three factors: warmth (W), protectiveness
      (P) and authoritarianism (A). W was most strongly predicted by parental
      personality and psychopathology, parental marital quality, and child temperament.
      P and A were both most strongly predicted by parental educational level and
      religious fundamentalism. In addition, P was predicted by neurotic/anxious traits
      in both parent and child. For a number of variables that predicted W, the
      strength of the association was stronger when twins were reporting than when
      parents were reporting. CONCLUSIONS: Parenting is a complex, multi-determined set
      of behaviours that is influenced by parental personality, psychopathology, values
      and marital quality and by a range of child characteristics. W appears to be
      strongly influenced by parental and childhood temperament and vulnerability to
      psychiatric illness while P and A are more strongly influenced by 'sociological'
      factors such as religious affiliation and educational status.

PMID- 9153677
TI  - The interaction between mood and cognitive function studied with PET.
AB  - BACKGROUND: Experimentally induced depressed mood is a suggested model for
      retarded depression. We describe the neural response associated with induced mood
      and the locus of the interaction between systems mediating mood and cognitive
      function. METHODS: Normal subjects performed a verbal fluency task during induced
      elated and depressed mood states. Regional cerebral blood flow (rCBF) was
      measured as an index of neural activity using Positron Emission Tomography (PET).
      RESULTS: In both elated and depressed mood state rCBF was increased in lateral
      orbitofrontal cortex, rCBF was also increased in the midbrain in elated mood. In
      the depressed condition rCBF was decreased in rostral medial prefrontal cortex.
      Verbal fluency produced an expected increase of rCBF in left dorsolateral
      prefrontal, inferior frontal and premotor cortex, anterior cingulate and insula
      cortex bilaterally, the left supramarginal gyrus posteriorly and the thalamus.
      Activation in the verbal fluency task was attenuated throughout the left
      prefrontal, premotor and cingulate cortex and thalamus in both elated and
      depressed mood conditions. An attenuation of anterior cingulate activation was
      specific to depressed mood. CONCLUSIONS: Alteration of mood is associated with
      activation of orbitofrontal cortex which may be critical to the experience of
      emotion. The mood induced modulation of verbal fluency induced activations is
      consistent with resting state findings of decreased function in these regions in
      depressed patients. The present data suggest that resting state rCBF profile may
      represent the modulation of spontaneous activity in this network by a core system
      that is dysfunctional in depression.

PMID- 9153678
TI  - Correlation of auditory 'oddball' P300 with verbal memory deficits in
      schizophrenia.
AB  - BACKGROUND: The study attempts to recruit well known 'cognitive' event related
      potential measures as an objective estimate of cognitive and specific memory
      impairment in schizophrenia. METHODS: We examined 19 schizophrenic patients and
      28 healthy controls using an auditory discrimination task to elicit event related
      potentials, and a number of neuropsychological tests, including tests of general
      intellectual ability, putative frontal lobe function and verbal memory. RESULTS:
      The late positive deflection presumed to be associated with stimulus evaluation
      (P300) was of lower amplitude and had a longer latency in the patients compared
      with controls of similar age and sex. We found correlations between P300
      amplitude and latency, and neuropsychological performance scores in patients.
      There were correlations between decreased P300 amplitude and lower IQ and poorer
      memory performance, in particular, abnormal semantic clustering, discriminability
      and intrusion errors. Increased P300 latency was correlated with lower pre-morbid
      IQ, poorer total memory scores and serial clustering, but paradoxically less
      relative retrieval deficit and fewer intrusion errors. CONCLUSIONS: These
      findings suggest that abnormal P300 is generally more likely to occur in patients
      with memory impairment.

PMID- 9153680
TI  - Factors predisposing to suspected offending by adults with self-reported learning
      disabilities.
AB  - BACKGROUND: This study investigated factors contributing to suspected offending
      behaviour by adults with a history of learning disabilities taken into custody at
      a city police station. METHODS: Adults charged with offences, and/or leaving
      custody, during a defined period, were identified as having a possible learning
      disability using a four-item questionnaire (Lyall et al. 1995 a). A comparison
      group, of similar age, sex and IQ, was identified from a database of young people
      with learning difficulties. Information was obtained on interview about each
      individual's medical, psychiatric, social and family histories and psychological
      assessments were undertaken. RESULTS: In contrast to the comparison group, those
      in the 'offending' group were more likely to have a history of the following:
      losing contact with their father, forensic contact in one or more family members,
      past homelessness, illicit drug use, experiencing an excess of recent life
      events, self-reported behavioural problems at school, truancy, childhood police
      contact and contact with probation services. All had histories of repeated
      offending. There was also an increased rate of drug/alcohol dependence. Only two
      subjects in the study group had a full-scale IQ below 70. CONCLUSIONS: These
      differences would suggest that the presence of childhood behavioural problems,
      offending behaviour by other family members, family separation and other social
      disruption and the development of drug and alcohol related problems are
      potentially the most important factors in trying to understand why one group
      engaged in criminal behaviour. The offending group had many characteristics in
      common with general offending populations.

PMID- 9153679
TI  - Brain activation during an auditory 'oddball task' in schizophrenia measured by
      single photon emission tomography.
AB  - BACKGROUND: The study examines the effect of an auditory discrimination task on
      regional brain perfusion in schizophrenic patients. METHODS: Twenty patients were
      examined with single photon emission tomography (SPET), both resting and
      performing an auditory two-tone 'oddball' discrimination task. Statistical
      parametric mapping (SPM'95) was used to identify local activation effects and
      correlations between event related potential measures and regional perfusion.
      RESULTS: Compared with rest, patients activated left superior temporal gyrus
      during the task, together with right caudate. There was a (negative) correlation
      between P300-amplitude and perfusion during the activation procedure in both
      caudate nuclei and in the left lingual gyrus. No correlations were observed with
      P300-latency. Compared with healthy volunteers examined in earlier studies, our
      patients showed no frontal activation. This might be due to slightly different
      task demands in this study, but more likely to activation-hypofrontality in
      schizophrenic patients compared with controls. CONCLUSION: Auditory
      discrimination tasks can be used in schizophrenic patients to control their
      'mental set' during brain perfusion studies with SPET. This approach can yield
      information about specific brain mechanisms associated with such tasks, and may
      make comparison with healthy volunteers easier.

PMID- 9153681
TI  - High prevalence of dementia among people with learning disabilities not
      attributable to Down's syndrome.
AB  - BACKGROUND: For many years, it has been known that dementia can occur in people
      with learning disabilities, but there have been few research studies. Studies
      that do quote rates for dementia show these to be high, but this important fact
      has received remarkably little attention. METHOD: Comprehensive psychiatric and
      medical assessments were undertaken on the whole population (ascertained as far
      as is possible) of people with learning disabilities aged 65 years and over
      living in Leicestershire, UK (N = 134), in order to ascertain rates of DCR
      defined dementia, and associated factors. RESULTS: Dementia was diagnosed in
      21.6%, against an expected prevalence of 5.7%, for a group with this age
      structure. The rate of dementia increased in successive age cohorts: 15.6% aged
      65-74 years; 23.5% aged 65-84 years; and 70.0% aged 85-94 years. People with
      dementia tended to be older, female, with more poorly controlled epilepsy, a
      larger number of additional physical disorders, less likely to be smokers and had
      lower adaptive behaviour scores than did the elderly people without dementia.
      They were more likely to live in health service accommodation. CONCLUSIONS:
      Dementia occurs at a much higher rate among elderly people with learning
      disabilities than it does among the general population; this is independent of
      the association between dementia and Down's syndrome. Whether this relates
      aetiologically to genetics, lack of brain 'reserve' or history of brain damage is
      yet to be determined.

PMID- 9153682
TI  - Structural factor analyses for medically unexplained somatic symptoms of
      somatization disorder in the Epidemiologic Catchment Area study.
AB  - BACKGROUND: Assess the latent structure of the DSM-III somatization symptoms and
      the stability of symptom patterns over time. METHODS: Cross-sectional and
      longitudinal covariation of symptoms of somatization disorder were investigated
      using structural equation models in a population-based data set from the
      Epidemiologic Catchment Area study. RESULTS: Medically unexplained physical
      complaints were discovered to cluster into three separate factors, consistent
      with the DSM-IV definition of somatization disorder, but one dominant general
      factor was defined, consistent with the DSM-III conceptualization. Individual
      symptom prevalences and factor structures were different for men and women. The
      factor structures remained stable at 1 year follow-up. Variations in the
      threshold of number of somatization symptoms required for diagnosis affected
      prevalence, sex ratio and temporal stability of the diagnosis. CONCLUSIONS: These
      population-based results support dimensional models of somatization. Implications
      for changing the threshold of the categorical diagnosis of somatization disorder
      and providing better care for these patients are given.

PMID- 9153683
TI  - Social phobia, avoidant personality disorder and atypical depression: co
      occurrence and clinical implications.
AB  - BACKGROUND: Increasing attention has been directed in recent years to the
      detection and treatment of psychiatric co-morbidity among depressed individuals.
      The overlap of social phobia (SP) and avoidant personality disorder (APD) has
      been well recognized and a relationship between these disorders and depression
      has been suggested. METHODS: The pattern and clinical implications of co
      morbidity of SP and APD with major depressive disorder (MDD), diagnosed by DSM
      III-R criteria, were studied among 243 out-patients presenting with depression.
      RESULTS: Overall, 26.7% of adults in our sample with MDD met criteria for SP and
      28.4% for APD. Almost two-thirds of depressed adults meeting criteria for social
      phobia or avoidant personality disorder met criteria for both (SP+APD). Depressed
      adults who met criteria for both SP+APD exhibited a significantly higher
      proportion of atypical depression (54.8%) compared with those with neither SP nor
      APD (31.1%). Among depressed patients, the co-occurrence of SP with APD was also
      associated with an earlier age of onset of MDD, a greater number of comorbid Axis
      I diagnoses, and greater impairment of social adjustment and assertiveness.
      CONCLUSIONS: Results confirm the overlap of SP and APD in a depressed population
      and the high prevalence of these disorders in MDD. They suggest that depressed
      individuals with both SP and APD but not SP alone are at particularly high risk
      for atypical depression and for social dysfunction in excess of that caused by a
      current major depression.

PMID- 9153684
TI  - Assessment of the dysexecutive syndrome in schizophrenia.
AB  - BACKGROUND: Cognitive neuropsychological theories hypothesize a role for frontal
      lobe executive deficits in the aetiology of schizophrenic symptoms. The study
      examined the performance of a schizophrenic group on the Behavioural Assessment
      of the Dysexecutive Syndrome (BADS; Wilson et al. 1996), a test battery which
      assesses the 'everyday' difficulties associated with the dysexecutive syndrome.
      Performance of the schizophrenics was contrasted with that of brain injured and
      healthy volunteer groups. METHODS: Matched groups of 31 schizophrenic patients,
      35 patients with brain injuries and 26 healthy volunteers were administered the
      BADS. Patients were also given tests of general intelligence and memory. Patients
      and their relatives/carers also completed a questionnaire rating day-to-day
      failures of executive functioning. RESULTS: Schizophrenic and brain-injured
      patients showed impairment on the BADS, compared to healthy controls. There were
      no significant differences between the two patient groups. Significant impairment
      was found in a subgroup of 16 schizophrenics who showed otherwise intact general
      intellectual functioning, suggesting the existence of a specific executive
      deficit. Among the schizophrenic patient group there was evidence of a
      dissociation between executive and memory impairments. A significant correlation
      existed between performance on the BADS and relatives ratings of executive
      problems for the brain injured group, but not for the schizophrenic group.
      CONCLUSIONS: The BADS is a useful tool for identifying executive deficits in
      people with a diagnosis of schizophrenia, especially those who are otherwise
      generally intellectually intact. This is particularly important in the context of
      rehabilitation and community transition programmes.

PMID- 9153685
TI  - Family caregiving: measurement of emotional well-being and various aspects of the
      caregiving role.
AB  - BACKGROUND: Past research and instrument development in caregiving have focused
      on specific aspects of caregiving or specific disability groups. This paper
      reports the scale characteristics of a new generic instrument developed to assess
      the experience of caregiving, and the social and emotional well-being of
      caregivers and a comparison group of 'non-caregivers'. METHODS: Using computer
      assisted telephone technology, a random survey of 26000 households was conducted
      in Victoria, Australia to identify and interview 976 caregivers of people who
      were aged or had a long-term illness or disability of any kind, and 219 non
      caregivers. Both groups were re-interviewed after 15 months. Scales administered
      on each occasion to caregivers and non-caregivers included life satisfaction,
      positive and negative affect, social support and overload; and to caregivers,
      caring role satisfaction, resentment and anger, and, in relation to the care
      recipient, measures of help provided and needed, severity of disability and
      behaviour problems. RESULTS: On each occasion and with each sample all scales
      demonstrated a satisfactory reliability. With a subsample of caregiver-care
      recipient dyads (N = 67), caregiver reports of severity of disability, level of
      helped needed and provided were validated externally by clinician assessments.
      CONCLUSIONS: A comprehensive instrument to assess the experience of caregiving
      was developed. It is relevant to a broad range of ages, levels and types of
      disability and care provided; and, in assessing health and well-being, to both
      caregivers and non-caregivers. Scales, including both positive and negative
      dimensions, have demonstrated good internal consistency on two occasions. The
      instrument is potentially useful in a range of research and practical settings.

PMID- 9153686
TI  - Does the genotype for schizophrenia often remain unexpressed because of
      canalization and stochastic events during development?
AB  - BACKGROUND: It has been well established in the literature that a strong genetic
      component exists for schizophrenia. Available data are compatible with the
      hypothesis that for most cases of schizophrenia, the genetic component consists
      of multiple genes acting in an additive manner with the genotype for
      schizophrenia being present when the number of genes is greater than a threshold
      number. Twin studies suggest that the genotype for schizophrenia is unexpressed
      in some individuals who carry it. This phenomenon of reduced penetrance has led
      to a diversity of hypotheses concerning the aetiology of schizophrenia. Based on
      a review of the literature a neurodevelopmental model is proposed for
      schizophrenia that involves the actions of the schizophrenia genotype,
      canalization and stochastic events. CONCLUSIONS: The schizophrenia genotype is
      programmed to disrupt the migration of neuronal cells in the developing cortex
      during the second trimester, resulting in impaired embryogenesis. The presence of
      a specific lesion is the reason for the onset of schizophrenia later in life. The
      genotype for schizophrenia often remains unexpressed, or demonstrates variable
      expressivity, because of the actions of canalization and stochastic events that
      may allow migrating neuronal cells to reach or approach the target data.
      Stochastic events also influence whether canalization will be successful,
      therefore, chance plays a major role under normal conditions in determining
      whether the schizophrenia genotype will be expressed. Certain environmental
      factors acting during early development, such as high temperature resulting from
      maternal illness, may increase the penetrance of the schizophrenia genotype.

PMID- 9153687
TI  - Cognitive factors in source monitoring and auditory hallucinations.
AB  - BACKGROUND: In order to elucidate further the cognitive processes underlying
      auditory hallucinations, an experiment investigating delayed and immediate source
      monitoring for positive, negative and neutral verbal material was conducted with
      schizophrenic patients. METHODS: Patients experiencing auditory hallucinations,
      patients not experiencing auditory hallucinations and normal subjects
      participated in a word association task, rating their responses for how much a
      self-generated thought was their own, how controllable and involuntary it was and
      their confidence in these ratings. A delayed source monitoring test in which
      subjects had to recall the source (self or experimenter) of the words from the
      association task was also administered. RESULTS: Hallucinators showed a greater
      bias towards external attribution of their thoughts compared with both control
      groups for immediate attributions of source, but not for delayed attributions.
      Hallucinators showed a bias towards external attribution of emotional material
      for immediate source monitoring and all subjects showed a bias towards
      misattribution of positive material to an external source and negative material
      to an internal source for the delayed source monitoring task. CONCLUSIONS: These
      findings appear to be most consistent with theories proposing that hallucinations
      result from an external attributional bias for internal events. The implications
      of these results for research and practice are also discussed.

PMID- 9153688
TI  - The cost consequences of changing the hospital-community balance: the mental
      health residential care study.
AB  - BACKGROUND: Altering the balance of provision between hospital and community care
      is a key and often contentious component of mental health care policy in many
      countries. Implementation of this policy in the UK has been slowed by the
      apparent shortage of suitable community accommodation for people with long-term
      needs for care and support. Among the consequences could be the silting up of
      hospital beds by people who could be supported more appropriately elsewhere, in
      turn denying in-patient treatment to people with acute psychiatric problems and
      unnecessarily pushing up health service expenditure. METHODS: Using data
      collected in a survey of hospital and residential accommodation services and
      their residents in eight areas of England and Wales, the cost components of
      today's balance of care were explored. Comprehensive costs were calculated and
      their associations with resident characteristics examined using multiple
      regression analyses. RESULTS: On a like-with-like basis, the costs of hospital in
      patient treatment for inappropriately placed patients greatly exceeded the costs
      of community-based care. CONCLUSION: Further reduction of hospital beds, however,
      is not the panacea for an appropriate balance of mental health care, given the
      unknown but potentially considerable extent of unmet demand, as well as the
      impact of previous in-patient bed reductions apparent in the services surveyed.
      Rather, service providers and purchasers should focus on developing community
      based care (including increased provision of 24-hour nursed beds) by ensuring
      that resources released through earlier closure programmes have been redeployed
      for their intended use and by accessing additional pump-priming or bridging
      resources.

PMID- 9153689
TI  - Hostility and registered sickness absences: a prospective study of municipal
      employees.
AB  - BACKGROUND: Prior evidence on the relationship between hostility and minor health
      problems is limited to cross-sectional self-report studies. In the present study,
      this relationship was examined prospectively. METHODS: Hostility of 1077
      municipal employees was measured by a questionnaire survey and minor health
      problems by using 4-year register-based absence data including medically
      certificated diagnoses. RESULTS: High hostility predicted a high total number of
      long-term sickness absence spells among men, but not among women. In separate
      diagnostic categories (musculo-skeletal, traumas and injuries, respiratory),
      hostility related positively and linearly to absences due to traumatic causes and
      curvilinearly (U-shape) to absences due to musculo-skeletal causes. Controlling
      the effects of health risk behaviour and demographic background did not
      significantly change these figures. However, health risk behaviour moderated the
      relations of hostility to overall long-term sickness absences, and to traumatic
      and musculo-skeletal absences, being significantly stronger in high-risk groups.
      No association was found between hostility and non-certificated short-term
      absence spells. CONCLUSIONS: The results suggest that hostility plays a role in
      the aetiology of minor health problems.

PMID- 9153690
TI  - The hippocampus in schizophrenia: lateralized increase in neuronal density and
      altered cytoarchitectural asymmetry.
AB  - BACKGROUND: The histological basis of schizophrenia is unknown, but it appears to
      affect the hippocampal and neocortical cytoarchitecture. Some cytoarchitectural
      parameters normally differ between the two cerebral hemispheres. Moreover,
      schizophrenia is associated with altered structural cerebral asymmetry. However,
      few cytoarchitectural studies of schizophrenia have taken the question of
      asymmetry fully into account. METHODS: We performed a morphometric post mortem
      study of neuronal density in sections from the left and right hippocampus
      (dentate gyrus, CA4, CA3, CA1 and subiculum) of 22 schizophrenics and 18 normal
      subjects. We also determined the correlations of neuronal density between pairs
      of subfields as an index of their inter-relationship; a previous study had found
      correlations in the left but not the right hippocampus of normal subjects.
      RESULTS: There were three differences in the schizophrenics compared to the
      controls. (1) neuronal density was increased in right CA3 (by 25%) and right CA1
      (by 22%); (2) neuronal density correlated strongly between homologous left and
      right subfields (i.e. inter-hippocampally) for CA4, CA3, CA1 and subiculum, in
      normals this occurs only for dentate gyrus and CA4; and (3) intrahippocampal
      correlations of neuronal density between pairs of subfields were similar in both
      hippocampi of the schizophrenia cases, unlike their asymmetrical distribution in
      controls. CONCLUSIONS: The alterations may be part of the histological substrate
      of schizophrenia. The nature of the findings is consistent with a
      neurodevelopmental origin, and with a disease process that affects cerebral
      asymmetry and leaves its imprint upon the hippocampal cytoarchitecture.

PMID- 9153691
TI  - Adolescent suicidal behaviours: a population-based study of risk.
AB  - BACKGROUND: Reports of adolescent suicidal behaviour have generally derived from
      clinical settings but population-based studies are likely to provide a clearer
      epidemiological view. METHODS: Non-fatal suicidal behaviours were studied in 1699
      Australian 15- to 16-year-old secondary school students at 44 schools in the
      state of Victoria, Australia. Self-reported episodes of self-harm were
      characterized using items from the Beck Suicide Intent Scale. RESULTS: The 12
      month weighted prevalence estimate for deliberate self-harm was 5.1%. The
      commonest forms were self-laceration (1.7%), self-poisoning (1.5%) and deliberate
      recklessness (1.8%). Self-poisoning and self-laceration were commoner in girls.
      The prevalence of 'true suicide attempts' was 0.2%. Most self-harmers did not
      perceive death as likely, plan self-harming episodes at length or inform others
      of the episodes. Psychiatric morbidity had the strongest association with self
      harm, an association which held for all subtypes. Antisocial behaviour and
      substance abuse were associated with self-harm in girls but not boys. Sexual
      activity was independently associated with self-harm in both genders.
      CONCLUSIONS: Deliberate self-harm was common but the great majority of episodes
      were not 'true suicide attempts'. It is, therefore, possible that attributable
      mortality and morbidity may be greater in self-harmers without definite suicidal
      intent.

PMID- 9153692
TI  - Persisting improvement in complaint-related cognitions initiated during medical
      consultations in functional abdominal complaints.
AB  - BACKGROUND: Previously it was shown that during a series of out-patient
      consultations dysfunctional complaint-related cognitions and anxiety diminished
      significantly in patients with functional abdominal complaints (IBS). The aim of
      the present study was to assess the maintenance of positive changes initiated
      during medical consultations in the patients' complaint-related cognitions and
      anxiety, as well as the influence of these cognitions on the severity of the
      complaints, 6 months after the first visit to the out-patient clinic. METHODS:
      One hundred and five consecutive patients with IBS referred by their general
      practitioners to the out-patient clinic for internal medicine completed
      questionnaires about their complaints and their complaint-related cognitions and
      anxiety before the first and after the last out-patient visit and again at follow
      up, 6 months after the first out-patient consultation. RESULTS: Positive changes
      in the patients' complaint-related cognitions during the consulting period were
      found to persist during the follow-up period. Improvement in abdominal complaints
      at follow-up was found to be related to the level of the patients' state anxiety,
      fear of cancer, and catastrophizing cognitions at the last out-patient visit.
      CONCLUSIONS: Medical consultations can bring about long-lasting positive changes
      in prognostically unfavourable cognitions and anxiety. These changes appear to be
      related to a better outcome of IBS.

PMID- 9153693
TI  - Predictors of treatment outcome for major depression in primary care.
AB  - BACKGROUND: A randomized controlled clinical trial compared three treatments for
      major depression in primary care. Ninety-one patients were randomized to receive
      either problem-solving, or amitriptyline with standard clinical management, or
      drug placebo with standard clinical management. This paper examines the possible
      predictive value of a range of demographic clinical and personality variables in
      determining outcome. METHODS: To examine the interaction between treatment group
      and predictor variables, analyses of co-variants were carried out for two outcome
      measures: the Hamilton Rating Scale for Depression and the Beck Depression
      Inventory. Predictor variables were also entered into a stepwise forward logistic
      regression in which patients were categorized as recovered or not recovered.
      RESULTS: None of the predictor variables examined interacted with treatment to
      predict outcome. Patients with a longer duration of illness, chronic social
      difficulties, or definite, as opposed to probable, major depression had a poorer
      outcome at the end of treatment, irrespective of treatment group. CONCLUSIONS:
      The findings in this study do not enable clear guidelines to be given as to which
      patients with major depression in primary care might benefit from either a
      psychological or pharmacological treatment.

PMID- 9153694
TI  - HMPAO SPET does not distinguish obsessive-compulsive and tic syndromes in
      families multiply affected with Gilles de la Tourette's syndrome.
AB  - BACKGROUND: Gilles de la Tourette's syndrome (GTS) is a familial neuropsychiatric
      disorder characterized by tics and obsessive-compulsive behaviours (OCB).
      Previous HMPAO SPET studies of subjects with GTS have shown hypoperfusion of
      striatal and frontal areas. Studies of patients with primary obsessive-compulsive
      disorder have shown, in contrast, hyperperfusion of similar areas. METHODS:
      Twenty subjects from five families affected by GTS, including individuals with
      OCB but no tics, were examined using HMPAO SPET. RESULTS: There were
      abnormalities of regional cerebral perfusion in individuals with GTS, OCB and
      tics. Hypoperfusion was in striatal, frontal and temporal areas. There was no
      hyperperfusion. CONCLUSIONS: Regional cerebral blood flow patterns in individuals
      with OCB in families affected by GTS are comparable to their relatives with GTS
      and differ from individuals with primary OCD in the absence of a family history
      of tic disorders.

PMID- 9153695
TI  - Introduction to primer on computers and information technology.

PMID- 9153696
TI  - Evaluation of tracheobronchial disease with helical CT with multiplanar and three
      dimensional reconstruction: correlation with bronchoscopy.
AB  - The advantage of volumetric computed tomography in the thorax is the possibility
      of acquiring both multiplanar and three-dimensional (3D) images, thus enabling
      precise diagnosis and evaluation of extent of disease involving the airways.
      Multiplanar and 3D images appear to be useful for global understanding of the
      status of the tracheobronchial tree, particularly for evaluation of focal
      stenosis of the airways. Such images seem to be especially useful in evaluating
      the longitudinal extent of airway lesions, thus providing valuable information
      for preparing a road map for bronchoscopy, for surgical planning, and for follow
      up of treatment response. However, multiplanar and 3D images do not appear to be
      useful in lesion detection or evaluation of transaxial extension. Multiplanar and
      3D images also seem to be helpful in demonstrating whether a lesion is
      endobronchial, submucosal, or peribronchial. The quality of such images appears
      to be excellent or good in almost all patients.

PMID- 9153697
TI  - The costal cartilages in health and disease.
AB  - The costal margin, although imaged in many routine radiologic examinations, has
      been ignored in the radiology literature. Calcification of the costal cartilages
      follows gender-related patterns and is generally not evident radiographically
      until after the age of 30 years. Diffuse enlargement of the costochondral
      junctions may alert the astute observer to the presence of systemic diseases such
      as acromegaly and rickets. Focal masses have a subtle appearance on plain
      radiographs and may be better imaged with computed tomography (CT) or magnetic
      resonance imaging. Chondrosarcoma of the costal margin typically appears as an
      expansile mass with coarse calcifications and an associated soft-tissue mass.
      Radiographic and CT features of costochondritis include chondral enlargement or
      destruction, low-attenuation cartilage at CT, associated soft-tissue swelling,
      and localized peripheral cartilage calcification. There appears to be an
      association between heavy premature costal cartilage calcification and certain
      systemic conditions, such as malignancy, autoimmune disorders, chronic renal
      failure, and thyroid disease, particularly Graves disease.

PMID- 9153698
TI  - Takayasu arteritis: protean radiologic manifestations and diagnosis.
AB  - Diagnosis of Takayasu arteritis is difficult because the clinical features are
      similar to those of other diseases. In early-phase Takayasu arteritis, computed
      tomography (CT) and magnetic resonance (MR) imaging show thickening of the aortic
      wall. Late-phase Takayasu arteritis has been classified into four types: classic
      pulseless disease (type I), a mixed type (type II), the atypical coarctation type
      (type III), and the dilated type (type IV). In late-phase Takayasu arteritis,
      angiography usually demonstrates luminal changes such as stenosis, occlusion, or
      aneurysmal dilatation of the aorta and pulmonary artery and their branches.
      However, absence of such luminal changes does not exclude the possibility of
      early-phase Takayasu arteritis. Improvement in the clinical findings and
      subsidence of the active inflammatory process can be expected with early steroid
      treatment. Familiarity with the varied chest radiographic, angiographic, CT, and
      MR imaging features of Takayasu arteritis will permit earlier diagnosis and
      treatment.

PMID- 9153699
TI  - MR imaging of congenital anomalies of the thoracic veins.
AB  - Congenital anomalies of the thoracic veins are infrequent but important
      developmental abnormalities. Thoracic venous anomalies can be classified as
      systemic or pulmonary. Systemic venous anomalies are often incidental findings,
      whereas pulmonary venous anomalies are more likely to manifest with cyanosis and
      to be associated with congenital cardiac abnormalities, especially atrial septal
      defect. Magnetic resonance (MR) imaging provides excellent delineation of the
      abnormal vessels and associated cardiac defects. Conventional spin-echo (SE)
      techniques show blood flow as a signal void and are sufficient for demonstrating
      the aberrant venous anatomy in most cases. Gradient-echo images show flowing
      blood as high signal intensity and are useful for clarifying the course of
      anomalous veins when vessel walls are difficult to visualize on SE images. Phase
      contrast images are valuable for ascertaining the direction of blood flow and
      thus provide a physiologic method of distinguishing the vertical vein of
      anomalous pulmonary venous return from a left superior vena cava. MR imaging is
      useful for delineating both the thoracic venous and accompanying intracardiac
      anomalies and is a valuable, complementary technique to echocardiography,
      angiography, and computed tomography in the evaluation of patients with these
      abnormalities.

PMID- 9153700
TI  - Pitfalls and sources of error in staging rectal cancer with endorectal us.
AB  - Endorectal ultrasound (US) is an accurate technique for local staging of rectal
      cancer. Because the choice of surgery depends on the level of tumor invasion and
      lymph node involvement, the surgeon relies largely on endorectal US findings when
      planning treatment. However, staging inaccuracies can occur due to over or
      underestimation of tumor depth, misinterpretation of lymph node involvement, and
      operator inexperience. Technical pitfalls in US of the rectal wall include
      proximity of the lesion to the anal verge, improper balloon inflation, a
      nonperpendicular imaging plane, shadowing artifacts due to air or stool,
      reverberation artifacts, refraction artifacts, and a transducer gain setting that
      is too high. Sources of error in tumor staging with endorectal US include
      interpretation differences, endosonologist bias, tumor location, tumor stenosis,
      peritumoral inflammation, postbiopsy and postsurgical changes, post irradiation
      changes, hemorrhage, and pedunculated or villous tumors. Node size and appearance
      are not reliable indicators of lymph node involvement. Awareness of these sources
      of error will improve the technical quality of endorectal US studies and allow
      more accurate tumor staging.

PMID- 9153701
TI  - MR imaging in male infertility.
AB  - In patients with male infertility, endorectal magnetic resonance (MR) imaging
      provides high-resolution images of the prostate gland and ejaculatory apparatus.
      The multiplanar capability of MR imaging allows production of a detailed map of
      the reproductive tract for guiding treatment. Causes of male infertility can be
      classified as congenital, acquired, infectious, or hormonal. Wolffian duct
      abnormalities include agenesis of the kidney, vas deferens, or seminal vesicle
      and cysts of the vas deferens, seminal vesicle, or urogenital sinus-ejaculatory
      duct. Mullerian duct abnormalities are less common and consist of mullerian duct
      cysts and utricle cysts. Cowper duct cysts and peripheral-zone prostatic cysts
      are acquired causes of male infertility. Prostatitis, an infectious cause of male
      infertility, may mimic carcinoma on long repetition time/echo time images. A low
      testosterone levels is one of the hormonal causes of male infertility. Pitfalls
      in the interpretation of MR images can be avoided by familiarity with normal and
      abnormal findings in patients with male infertility.

PMID- 9153702
TI  - Politically correct diseases.

PMID- 9153703
TI  - Pelvic endometriosis: MR imaging spectrum with laparoscopic correlation and
      diagnostic pitfalls.
AB  - Endometriosis is a common multifocal disease involving a number of anatomic sites
      in the pelvis. Although laparoscopy is the standard of reference for diagnosis,
      magnetic resonance (MR) imaging is a noninvasive method for evaluating areas
      inaccessible to laparoscopy. A large endometrioma (> or = 1 cm in diameter)
      appears as a homogeneously hyperintense mass on T1-weighted MR images and as a
      low-signal-intensity mass with areas of high signal intensity on T2-weighted
      images. A small endometrioma may be indicated when a pelvic mass less than 1 cm
      in diameter is hyperintense on T1-weighted images irrespective of its appearance
      on T2-weighted images. Endometriosis may also manifest as multiple, homogeneously
      hyperintense cysts on T1-weighted images. Involvement of the alimentary tract or
      bladder can appear as areas of high signal intensity. Although MR imaging is
      limited in its ability to depict small endometrial implants and adhesions, the
      advantages of MR imaging over laparoscopy include the ability to characterize
      endometriotic lesions and to evaluate extraperitoneal sites of involvement,
      contents of a pelvic mass, or lesions hidden by dense adhesions. The roles of the
      two modalities are therefore complementary. Knowledge of the variety of MR
      imaging appearances of endometriosis and organ involvement within the pelvis is
      important for guiding a subsequent laparoscopic examination.

PMID- 9153704
TI  - Glenohumeral instability: evaluation with MR arthrography.
AB  - Magnetic resonance arthrography is superior to other imaging techniques in
      evaluation of the glenohumeral joint. Normal variants that can be diagnostic
      pitfalls include the anterosuperior sublabral foramen, the Buford complex, and
      hyaline cartilage under the labrum. Anteroinferior dislocation is the most
      frequent cause of anterior glenohumeral instability and produces a constellation
      of lesions (anteroinferior labral tear, classic and osseous Bankart lesions, Hill
      Sachs lesion). Variants of anteroinferior labral tears include anterior
      labroligamentous periosteal sleeve avulsion and glenoid labral articular
      disruption. Anterior glenohumeral instability can also involve tears of the
      anterior or anterosuperior labrum or the glenohumeral ligaments. Posterior
      glenohumeral instability can involve a posterior labral tear, posterior capsular
      stripping or laxity; fracture, erosion, or sclerosis and ectopic ossification of
      the posterior glenoid fossa; reverse Hill-Sachs lesion; McLaughlin fracture; or
      posterosuperior glenoid impingement. Superior labral anterior and posterior
      lesions involve the superior labrum with varying degrees of biceps tendon
      involvement.

PMID- 9153705
TI  - MR imaging of the infrapatellar fat pad of Hoffa.
AB  - The infrapatellar fat pad of Hoffa is an intracapsular structure that is
      routinely visualized on magnetic resonance images of the knee. Because disease in
      this region is not uncommon, it is important to be familiar with the various
      pathologic entities that may occur here. Abnormalities that are intrinsic to this
      fat pad include Hoffa disease, intracapsular chondroma, localized nodular
      synovitis, postarthroscopy and postsurgery fibrosis, and shear injury. In
      addition, the infrapatellar fat pad may be involved secondarily from extrinsic
      processes, including articular disorders (eg, joint effusion, intraarticular
      bodies, meniscal cyst, ganglion cyst, cyclops lesion), synovial abnormalities
      (eg, pigmented villonodular synovitis; hemophilia; synovial hemangioma; primary
      synovial chondromatosis; chondrosarcoma; lipoma arborescens; rheumatoid,
      seronegative, and septic arthritis; arthritis associated with inflammatory
      intestinal disorders; synovitis associated with primary osteoarthritis), and
      anterior extracapsular abnormalities. The approach to pathologic processes
      involving the infrapatellar fat pad of Hoffa is simplified when one is familiar
      with regional anatomy and possible differential diagnostic considerations.

PMID- 9153706
TI  - Biphasic contrast-enhanced multisection dynamic MR imaging of the liver:
      potential pitfalls.
AB  - Biphasic contrast material-enhanced dynamic magnetic resonance (MR) imaging is an
      important technique for evaluating liver disease. However, several potential
      diagnostic pitfalls may be encountered, including lobar, segmental, subsegmental,
      and subcapsular hyperperfusion abnormalities; early-enhancing pseudolesions,
      particularly in the medial segment of the left hepatic lobe; heterogeneous
      hyperperfusion abnormalities throughout the liver; and hypointense pseudolesions
      due to vascular artifacts, unenhanced hepatic vessels, partial volume artifacts,
      magnetic susceptibility artifacts, and regenerative nodules in cirrhosis. These
      abnormalities sometimes have appearances similar to those of true lesions or
      tumor spread to the surrounding liver parenchyma on arterial-dominant phase
      dynamic MR images. In most cases, however, no corresponding abnormalities are
      seen with other pulse sequences or on delayed-phase MR images. In addition,
      hyperperfusion abnormalities due to readily recognizable causes are often found
      in characteristic locations and thus can be differentiated from true tumors. An
      understanding of the causes of these potential pitfalls and how to avoid them
      will help radiologists understand and correctly interpret images.

PMID- 9153707
TI  - Artifacts and pitfalls in MR imaging of the orbit: a clinical review.
AB  - High-resolution magnetic resonance (MR) imaging of the orbit has become widely
      accepted as a valuable diagnostic technique. However, there are a number of
      artifacts and pitfalls associated with orbital MR imaging. Chemical shift
      artifacts may be induced by orbital fat or silicone oil used to treat retinal
      detachment. Motion artifacts are caused primarily by unavoidable globe motion
      during imaging. Artifacts due to a nonuniform magnetic field are particularly
      noticeable at air-tissue interfaces but may also be caused by incomplete fat
      saturation or highly magnetic materials near the orbit. Protocol errors may cause
      artifacts such as saturation, phase wraparound, truncation, shading, and partial
      volume artifacts. This information can be used to improve orbital image quality
      and avoid misinterpretation of image artifacts. Use of fat saturation, silicone
      saturation, and careful patient screening for metal near the eyes and instruction
      to reduce motion can help reduce the occurrence of artifacts. In addition,
      optimal imaging technique is essential and should include use of proper surface
      coils, plane of section, and pulse sequences.

PMID- 9153708
TI  - Intralobar sequestration: radiologic-pathologic correlation.
AB  - Intralobar sequestration accounts for 75% of pulmonary sequestrations. The lesion
      consists of lung tissue that lacks normal communication to the tracheobronchial
      tree, has systemic arterial supply, and shares the pleura of the parent lobe. The
      majority of intralobar sequestrations are probably acquired lesions. Patients
      usually present before the age of 20 years with recurrent infection. At
      pathologic examination, intralobar sequestration is characterized by inflammation
      and fibrosis. At radiologic examination, intralobar sequestration typically
      appears as a consolidation or mass, with or without cavitation, within a lower
      lobe. In many cases, cystic change may be present within the affected lobe.
      Identification of a systemic arterial supply supports the diagnosis. Patients are
      treated with surgical excision, and prognosis is favorable.

PMID- 9153709
TI  - Flat-panel digital radiology with amorphous selenium and active-matrix readout.
AB  - Future imaging techniques will be capable of high image quality, fast
      acquisition, compactness, and versatile operation. A flat-panel imager that is
      expected to achieve these goals is under development. It consists of a thin layer
      of amorphous selenium that converts x rays directly to an electric charge and a
      thin-film electronic circuit, or active matrix, to read out the electronic signal
      directly to a computer host. The advantages of amorphous selenium include high
      resolution and low noise without loss of signal strength. The advantages of the
      active matrix are real-time readout, flexible design parameters, and compactness
      of the readout structures. A prototype of this imager has been built and
      operated, and initial images (of an x-ray test bar pattern and a hand phantom)
      have been acquired. Although the prototype was built to test scientific
      principles and many possibilities for optimization remain, the images already
      possess the quality necessary for many radiographic procedures. A large range of
      current and new applications exist for this imager.

PMID- 9153710
TI  - RadNotes: a novel software development tool for radiology education.
AB  - RadNotes is a novel software development tool that enables physicians to develop
      teaching materials incorporating text and images in an intelligent, highly usable
      format. Projects undertaken in the RadNotes environment require neither
      programming expertise nor the assistance of a software engineer. The first of
      these projects, Thoracic Imaging, integrates image teaching files, concise
      disease and topic summaries, references, and flash card quizzes into a single
      program designed to provide an overview of chest radiology. RadNotes is intended
      to support the academic goals of teaching radiologists by enabling authors to
      create, edit, and electronically distribute image-oriented presentations.
      RadNotes also supports the educational goals of physicians who wish to quickly
      review selected imaging topics, as well as to develop a visual vocabulary of
      corresponding radiologic anatomy and pathologic conditions. Although Thoracic
      Imaging was developed with the aim of introducing chest radiology to residents,
      RadNotes can be used to develop tutorials and image-based tests for all levels;
      create corresponding World Wide Web sites; and organize notes, images, and
      references for individual use.

PMID- 9153711
TI  - Image presentation in digital radiology: perspectives on the emerging DICOM
      display function standard and its application.
AB  - DICOM (Digital Imaging and Communications in Medicine) Working Group XI, formerly
      called ACR/NEMA (American College of Radiology/National Electrical Manufacturers'
      Association) Working Group XI, is currently developing a display function
      standard. The main objective of the standard is to define mathematically a
      display function for all image presentation systems. As a secondary objective,
      the standard aims at providing similarity in gray-scale perception for a given
      image between display systems of different luminance and at facilitating
      efficient utilization of the available digital input levels of a display system.
      The design of the display function incorporates the concept of perceptual
      linearization. The proposed standard applies to monochrome image presentation
      devices such as cathode ray tube monitor-display controller systems and digital
      laser image printers. The standard does not eliminate the use of application
      specific display functions but rather ensures their effectiveness. Neither does
      the standard guarantee equal information transfer between image presentation
      devices with different physical properties; it does, however, from the basis for
      applying image processing to compensate for such differences.

PMID- 9153713
TI  - Peutz-Jeghers syndrome and the hamartomatous polyposis syndromes: radiologic
      pathologic correlation.

PMID- 9153714
TI  - US case of the day. Benign cystic teratoma and testicular microlithiasis.

PMID- 9153715
TI  - General case of the day. Tracheobronchopathia osteochondroplastica.

PMID- 9153716
TI  - Breast imaging case of the day. Pure mucinous carcinoma with calcifying matrix.

PMID- 9153717
TI  - Pediatric case of the day. Cardiac rhabdomyoma.

PMID- 9153718
TI  - Epilepsy management: the general practitioner's perspective.
AB  - The opinions of general practitioners are considered important in the management
      of people with epilepsy. As part of an evaluation of the Comprehensive Epilepsy
      Service at The Queen Elizabeth Hospital in South Australia, 120 general
      practitioners were surveyed about their opinions of the Service and epilepsy
      issues using self-administered questionnaires. This enabled their opinions about
      the Service and epilepsy management to be elicited for future planning of
      effective service provision. The results of the evaluation showed that the
      Service needed to have a higher profile in the community regarding its existence
      and role. GPs considered they should manage the care of patients with epilepsy
      but a cooperative approach between GPs and the Service was important for
      successful management of difficult cases. Education about epilepsy for the
      patient and GP was also considered to be important for successful service
      provision. The GP's involvement in evaluation is essential for influencing the
      way in which health care services are delivered with regard to availability and
      accessibility for both themselves and their patients and should be encouraged to
      ensure effective epilepsy patient management.

PMID- 9153720
TI  - Epilepsy in a Dutch working population: are employees diagnosed with epilepsy
      disadvantaged?
AB  - The present study was designed to determine whether employees diagnosed with
      epilepsy, in contrast to comparable colleagues, encounter disadvantages in their
      professional careers. Attention was focused on education, job training, number of
      jobs performed, sickness absenteeism, accidents at work and wages. A group of 34
      employees diagnosed with epilepsy was selected and compared with matched, non
      epileptic colleagues. Slight differences between both groups were found for all
      items except for education. Only for wages was a statistically significant
      difference found. It is concluded that workers diagnosed with epilepsy and
      comparable colleagues both received the same educational and vocational training
      in order to reach their position. The data did not substantiate the proposition
      that employees diagnosed with epilepsy have poor attendance records, higher
      number of accidents in the workplace or that they are at a disadvantage in
      securing a job. However their salaries appear to be lower than the earnings of
      colleagues who hold comparable jobs.

PMID- 9153721
TI  - Season of birth: aetiological implications for epilepsy.
AB  - In most cases of epilepsy it is not possible to reach an aetiological diagnosis.
      Recent research points to a pre-perinatal disruption of the neurodevelopment as
      being the cause of at least some of these epilepsies of unknown aetiology. The
      object of this study was to corroborate this hypothesis from an epidemiological
      perspective and identify the most likely candidates for causes of this damage.
      The approach used was an analysis of the seasonal pattern of births in a large
      sample of epileptic patients discharged from NHS hospitals in England and Wales.
      The results illustrated that the seasonality of the births in the epileptic
      sample was significantly different from that of the general population, with an
      excess of patients born in December and January and a deficit of those born in
      September. This "seasonality' was present only in the patients born before the
      late 1950s. These results are suggestive of the existence of an aetiological
      factor for epilepsy with a seasonal presence in the environment and which is
      epileptogenic when acting in the pre-perinatal period. Prenatal infections,
      obstetric complications and nutrititional deficiencies are amongst the hypotheses
      developed on the nature of this agent(s).

PMID- 9153719
TI  - Factors influencing compliance with antiepileptic drug regimes.
AB  - Failure to comply with drug regimes is prevalent amongst patients with epilepsy
      and the consequence of this is often an increased risk of further seizures. This
      paper describes the level of, and influences upon, non-compliance with
      antiepileptic drug (AED) treatment. A postal questionnaire was sent to an
      unselected, community-based population of patients with epilepsy. This instrument
      included questions about patients' AED treatment, any related side-effects, and
      AED-taking behaviour. Univariate analysis showed that factors associated with
      compliance were patient age, how important patients felt it was to take drugs as
      prescribed, whether patients reported feelings of stigma, whether on mono- or
      polytherapy, whether they were experiencing any side-effects because of AEDs,
      whether patients had a regular arrangement to see their GP about epilepsy and how
      easy they found their GP to talk to. Multivariate analysis showed that the
      strongest predictors of non-compliance were feeling it was not very or not at all
      important to take AEDs as prescribed, being a teenager, being aged under 60 and
      being on monotherapy. Further implementation of educational programmes for people
      with epilepsy would help to improve levels of compliance thereby reducing the
      risk of unnecessary seizures.

PMID- 9153722
TI  - First ever seizures in the elderly: a seven-year follow-up study.
AB  - The clinical characteristics and prognosis of first ever seizures among the
      elderly (aged 65 years or more) were ascertained by following up a cohort of
      patients for 7 years. Twenty-three patients (mean age, 69.9 +/- 4.9 years) were
      registered in the Neurology Service between January 1988 and March 1989. Twelve
      patients had partial seizures with or without generalization. Three patients had
      status epilepticus, whereas ten had presented for single seizure. On presentation
      61.9% patients had neurological deficits and 73.9% had one or more systemic
      disorder. Head computerized tomography scans were abnormal in 17 cases. Seizures
      were attributed to acute stroke (26.1%), trauma (8.7%), subdural haematoma,
      degenerative diseases of the brain, cerebral metastasis, or central nervous
      system infections. The cause was unknown in 43.5% cases. At the end of 7 years,
      follow-up was complete for 15 patients (65.2%). The mean duration of follow-up
      was 68.6 +/- 28.7 months. Eight (53.3%) patients had died. Nine patients (60%)
      had attained 2-year remission of which three remained seizure free throughout.
      Six of the seven living patients were continuing antiepileptic drugs treatment.
      Forty per cent of them were dependent on others for the activities of daily life.

PMID- 9153723
TI  - Epilepsy or stereotypy? Diagnostic issues in learning disabilities.
AB  - Approximately 0.8% of people in the general population have epilepsy. Within this
      group are specific sub-populations who co-present with other additional
      conditions, learning disability being one such example. Epilepsy rates are the
      highest of all in this subgroup, between 21% and 50% and positively correlated
      with degree of learning disability. In addition, in the more severe categories,
      problems frequently arise when attempting to differentiate epileptic events from
      other phenomenon, such as stereotyped behaviours and involuntary movements. The
      individual is unable to communicate changes in consciousness and perception and
      observers often find it difficult to detect such changes, particularly with
      regard to the partial epilepsies. Intensive monitoring using EEG and video
      equipment can often prove valuable in such a situation in assisting carers to
      recognize epileptic episodes and respond accordingly.

PMID- 9153724
TI  - Weight gain with valproate or carbamazepine--a reappraisal.
AB  - The use of valproate has traditionally been held to be associated with a greater
      incidence of weight gain than that of other anticonvulsants. This paper presents
      an analysis of body weight data gathered during a randomized trial comparing
      valproate with carbamazepine in 260 children aged 4-15 years with newly-diagnosed
      epilepsy. There were more reports of weight gain as an adverse event in the
      valproate group than in the carbamazepine group (22 reports in 14 patients vs.
      nine reports in five patients). However, amongst the 211 patients (103 on
      valproate and 108 on carbamazepine) in whom objective weight measurements were
      taken during treatment, there were no differences between the treatments in
      percentage weight gain from baseline or incidence of excessive weight velocity.
      Eight patients reporting weight gain on valproate were switched to carbamazepine
      because of poor seizure control and/or adverse events including weight gain, but
      three of the four patients for whom body weight measurements were available
      continued to gain weight on carbamazepine. It is concluded that weight gain may
      be erroneously attributed to valproate treatment.

PMID- 9153725
TI  - A naturalistic study of the use of vigabatrin, lamotrigine and gabapentin in
      adults with learning disabilities.
AB  - Epilepsy is a common condition in people with learning disabilities with many
      patients continuing to suffer from seizures despite antiepileptic drug (AED)
      treatment. Although the advent of newer AEDs offers hope for better treatment,
      there is a need to compare the efficacy of each new AED in adults with both drug
      resistant epilepsy and learning disabilities. This retrospective casenote study
      involves the analysis of the outcome for those adults with learning disabilities
      treated with either vigabatrin, lamotrigine or gabapentin. The information
      obtained from the casenote analysis was used to both compare the efficacies of
      the three drugs and also the side-effects and drop-out rates, including reasons
      for drop-out. The total number of patients involved was 51 who underwent 71
      treatment episodes. All three AEDs had similar efficacies. Although vigabatrin
      was found to be associated with a higher incidence of behaviour problems,
      behaviour problems occurred with the other drugs as well. Lamotrigine caused
      increased seizures in 24% of patients, especially when prescribed at a higher
      dose. Gabapentin appeared to be associated with fewer serious side-effects.

PMID- 9153726
TI  - Pentylenetetrazol and strychnine convulsions in brain weight selected mice.
AB  - The seizure sensitivities to pentylenetetrazol (Ptz, 25-100 mg/kg) and strychnine
      (S, 2 mg/kg) were tested in two mice lines selected for large (LB) and small (SB)
      brain weight (brain weight difference being approximately 75 mg). The selection
      was based on a regression line connecting body and brain weight. SB mice were
      more sensitive to both drugs-their seizure latencies were shorter and lethality
      higher than in LBs. The seizures generated by Ptz and S are known to affect
      different neurotransmitter systems. The interstrain differences in seizure
      susceptibility are probably determined by SB mice nervous system traits rather
      than by differences in the particular neurochemical trait. The data on
      neocortical cytoarchitectonics obtained during our previous brain selection
      experiment could serve as the indirect evidence favouring such a suggestion.

PMID- 9153727
TI  - Centro-temporal benign epilepsy in Saudi children.
AB  - A review of 36 interictal EEGs compatible with the diagnosis of benign childhood
      epilepsy with centro-temporal spikes (BECTS) was made in this study. These
      children constituted 31% of the children with focal epileptic EEG activity
      observed in the same period. The dipolic spikes occurred either as a single focus
      (78%) or as two independent foci with a greater preponderance to the right (22%).
      The onset of seizures before the age of 5 years (Group I) is 53% and between 6
      and 10 years (Group II) is 47%. Clinical evaluation showed that 60% of the
      patients in Group I and 75% in Group II had lateralized seizures, although all of
      them were initially diagnosed as nocturnal generalized tonic-clonic seizures. A
      follow-up study showed 31% complete recovery, 47% seizure-free under medications,
      8% occasional seizures, 8% frequent seizures, and the rest 6% had a single
      seizure without medication. It is therefore concluded that the syndrome is common
      in Saudi Arabia and is usually unrecognized by the general physicians. The follow
      up of our patients so far confirms the excellent prognosis.

PMID- 9153728
TI  - Nocturnal epilepsies in adults.
AB  - We evaluated the clinical characteristics and the electroencephalographic (EEG)
      findings by long video-EEG monitoring in 64 successive patients with definite
      nocturnal seizures. Mental state, neurological examination, neuroimaging and EEG
      background were normal in all patients. Classification of epilepsies was possible
      in 42 out of 64 (66%) patients according to the revised Classification of
      Epilepsies and Epileptic Syndromes by the Commission on Classification and
      Terminology of International League Against Epilepsy (1989). Out of those 42
      patients, 33 (79%) had partial epilepsies, while 9 (21%) had generalized
      epilepsies. Response to antiepileptic drugs was excellent and only 4 (6%)
      patients had one seizure attack per year, two of them were on two antiepileptic
      drugs while the others were free of seizure on a single drug during the 2 years
      of follow-up. It seems that nocturnal seizures in adults form a new distinctive
      partial epileptic syndrome of a benign entity.

PMID- 9153729
TI  - Pseudoseizures and dissociative disorders: a common mechanism involving traumatic
      experiences.
AB  - Patients with psychogenic non-epileptic seizures (pseudoseizures) have been
      diagnosed as having conversion disorder or dissociative disorder. Pseudoseizure
      patients frequently report a history of physical and sexual abuse, and traumatic
      experience is considered part of the mechanism for producing dissociation.
      Pseudoseizures may be a manifestation of dissociative disorder, especially when a
      history of sexual or physical abuse is documented. A common mechanism involving
      traumatic experience may be present in both pseudoseizures and dissociative
      disorders. A complete neurodiagnostic evaluation along with an awareness of this
      relationship is needed to provide appropriate care for this patient population.

PMID- 9153730
TI  - Sexual behavior risk factors associated with bacterial vaginosis and Chlamydia
      trachomatis infection.
AB  - BACKGROUND AND OBJECTIVES: Few studies have demonstrated that bacterial vaginosis
      (BV) is associated with sexual behavior risk factors similar to those for other
      sexually transmitted diseases. The objective of this study was to determine the
      prevalence of these factors in a multivariate analysis of data from women
      infected with BV and Chlamydia trachomatis, and noninfected control subjects.
      GOALS: To study detailed sexual behavior risk factors reported by women with BV
      versus genital C. trachomatis infection (CT) and by non-BV-infected controls.
      STUDY DESIGN: A cross-sectional study was conducted with 1,011 women (Swedish
      Women's Health Study) recruited from family planning and youth clinics in
      Eskilstuna and Stockholm, Sweden (November, 1989-January, 1991). Participants
      were evaluated for the presence of BV, CT, Neisseria gonorrhoeae, Treponema
      pallidum, Trichomonas vaginalis, and human immunodeficiency virus, and
      interviewed in detail with respect to sexual behaviors. Statistical comparisons
      were made using chi-square test (Pearson and likelihood ratio), t test, and
      logistic regression multivariate analysis. RESULTS: Of 956 women eligible for
      analysis, the prevalence of BV and CT was 13.7% and 8.9%, respectively. The
      comparison group consisted of the remaining 825 women without BV. After excluding
      those with concomitant CT infection, there were 118 women with BV who were
      compared with 72 women with CT infection only. Sexual factors associated with BV
      versus the comparison group were a short-term relationship before and after
      sexual debut, high number of lifetime sexual partners, multiple partners during
      the last month, high orgasm ability, and more frequent history of group sex,
      sexual abuse, and rape. When the BV group was compared with the CT group, there
      were no significant differences in sexual activity risk factors, except for a
      higher frequency of experience of casual sex in the CT group. CONCLUSIONS:
      Bacterial vaginosis is associated with sexual behavior risk factors similar to
      those associated with genital CT infection.

PMID- 9153731
TI  - Fluoroquinolone treatment failure in gonorrhea. Emergence of a Neisseria
      gonorrhoeae strain with enhanced resistance to fluoroquinolones.
AB  - BACKGROUND AND OBJECTIVES: Although emergence of clinical isolates of Neisseria
      gonorrhoeae with decreased susceptibilities to fluoroquinolones and treatment
      failures in gonorrhea have been reported, there have been no clinical reports
      that fluoroquinolone treatments actually select quinolone-resistant strains, nor
      have isolates that exhibited clinically significant resistance been analyzed for
      resistance mechanisms. GOALS: To report a case of fluoroquinolone treatment
      failure in gonorrhea and emergence of a posttreatment isolate with enhanced
      resistance to fluoroquinolones; and to study mechanisms of quinolone resistance
      in the isolates from this patient. STUDY DESIGN: A patient with gonococcal
      urethritis treated with ofloxacin, 200 mg, three times daily for 5 days is
      described. Pretreatment and posttreatment isolates were tested for minimum
      inhibitory concentrations (MICs) of antimicrobial agents and analyzed for
      alterations in DNA gyrase and topoisomerase IV. They were also examined for
      ofloxacin uptake. RESULTS: Treatment failure with multiple doses of ofloxacin was
      observed in this case of gonorrhea. The pretreatment isolate showed decreased
      susceptibilities to fluoroquinolones (MIC of ofloxacin, 1.0 mg/l; MIC of
      ciprofloxacin, 0.25 mg/l), and had amino acid changes of Ser-91-->Phe in GyrA and
      Ser-87-->Ile in ParC. The posttreatment isolate exhibited an increase in
      resistance to fluoroquinolones (MIC of ofloxacin, 8.0 mg/l; MIC of ciprofloxacin,
      1.0 mg/l). This isolate had identical alterations in GyrA and ParC, but exhibited
      significantly reduced uptake of ofloxacin. This isolate also showed a small
      decrease in susceptibilities to cephalosporins. CONCLUSIONS: Alterations in DNA
      gyrase and topoisomerase IV confer clinically significant resistance to
      fluoroquinolones in N. gonorrhoeae strains. Treatment with multiple doses of
      fluoroquinolones is likely to bring about selection of more fluoroquinolone
      resistant strains of N. gonorrhoeae and to influence susceptibilities to
      cephalosporins.

PMID- 9153732
TI  - A population-based study of sexually transmitted disease incidence and risk
      factors in human immunodeficiency virus-infected people.
AB  - BACKGROUND AND OBJECTIVES: The Minnesota Department of Health conducts active
      surveillance for cases of human immunodeficiency virus (HIV) infection and
      passive surveillance for gonorrhea, Chlamydia trachomatis infection, and
      syphilis. The authors linked two computerized surveillance databases to assess
      gonorrhea incidence and risk factors for sexually transmitted disease (STD)
      acquisition among people with known HIV infection. STUDY DESIGN: People diagnosed
      with adolescent/adult HIV infection before 1993 and still alive as of December
      31, 1994 were compared to people diagnosed with gonorrhea, chlamydial infection,
      or primary/secondary syphilis in 1993 or 1994. Records were matched on name, date
      of birth, and gender. The incidence of reported gonorrhea was calculated and risk
      factors for STD acquisition were examined. RESULTS: Thirty (1.3%) of 2,315 HIV
      infected people were diagnosed with one or more STDs after HIV diagnosis (median
      interval: 3 years). There were 31 episodes of gonorrhea, seven episodes of
      chlamydial infection, and one episode of secondary syphilis. The gonorrhea
      incidence among HIV-infected people was high compared to the general population
      in Minnesota, even after stratifying by gender, age, and county of residence. STD
      acquisition was independently associated with female gender (odds ratio [OR] =
      3.8; 95% confidence interval [CI] = 1.7, 8.3) and residence in Hennepin County
      (OR = 2.9; 95% CI = 1.2, 7.1), the most populous county in Minnesota.
      CONCLUSIONS: Linkage of STD and HIV surveillance data is useful as a sentinel for
      high-risk sexual behavior among HIV-infected people, and it can help identify
      individuals who require additional interventions to prevent HIV transmission.
      State and local health departments should consider linking these data sources to
      assess trends and allocate resources.

PMID- 9153733
TI  - Comparison of E-test with agar dilution methods in testing susceptibility of N.
      gonorrhoeae to azithromycin.
AB  - BACKGROUND AND OBJECTIVES: The antimicrobial susceptibility pattern of Neisseria
      gonorrhoeae varies from one country to another and may also change with time. To
      monitor these variations and changes, it is desirable to have a method that is
      simple and reproducible. This study was undertaken to determine the in vitro
      susceptibility of N. gonorrhoeae to azithromycin and to assess the reliability of
      results obtained using E-test methodology for determination of the minimum
      inhibitory concentration (MIC) of azithromycin. STUDY DESIGN: The MICs for 135
      clinical isolates of N. gonorrhoeae were determined by a modified Kirby-Bauer
      method recommended by the National Committee for Clinical Laboratory Standards
      against penicillin, cefuroxime, ceftriaxone, norfloxacin, tetracycline,
      kanamycin, spectinomycin, and azithromycin. The MIC of azithromycin was
      determined by both the E-test and agar dilution method. All tests were done
      simultaneously. RESULTS: The MIC of azithromycin to all 135 isolates ranged from
      0.078 to 0.25 microgram/ml with the agar dilution method and from 0.016 to 0.50
      microgram/ml with the E-test. The MIC50 and MIC90 of azithromycin were 0.064
      microgram/ml and 0.125 microgram/ml, respectively, by the agar dilution method,
      whereas they are slightly higher by the E-test method. Seventy-six of the
      isolates were beta-lactamase producers and 69 were high-level tetracycline
      resistant N. gonorrhoeae. There was no difference in the MIC50 and MIC90 of
      azithromycin in these groups of isolates. The percentage agreement within the
      acceptable +/-1 log2 dilution difference between MICs obtained by E-test and
      those obtained by the agar dilution method was 97.8%. CONCLUSIONS: Azithromycin
      has a very good in vitro antigonococcal activity, and the E-test is a reliable
      method to determine the MIC of azithromycin against N. gonorrhoeae.

PMID- 9153734
TI  - Validity of self-reported sexual behaviors in adolescent women using biomarker
      outcomes.
AB  - OBJECTIVES: To determine the criterion-related validity of alternative approaches
      to the measurement of sexual intercourse using sexually transmitted diseases
      (STD) as a biomarker (the criterion). STUDY DESIGN: Analyses are based on an
      urban sample of 255 adolescent women, 15 to 19 years of age, treated for
      genitourinary infections with Neisseria gonorrhoeae, Chlamydia trachomatis or
      Trichomonas vaginalis who returned 3 months later for reexamination. Subjects
      completed self-administered questionnaires at enrollment and at 3 months.
      Genitourinary cultures were obtained at enrollment, 2 to 4 weeks later at a test
      of-treatment visit (TOT), and at 3 months. RESULTS: Two hundred fourteen of the
      255 adolescents also returned for a TOT culture; 186 of these 214 (73%) were free
      of infection 2 to 4 weeks after enrollment and 30% (56/186) acquired a subsequent
      STD by 3 months. The validity of questions about sexual behavior differed. No
      adolescent who denied interim intercourse by reporting "0" sexual partners or "0"
      coitions acquired an interval STD. Adolescents who denied regular intercourse
      (vaginal sex) or failed to indicate the number of interim coitions were at high
      risk for new STD-23% and 21%, respectively. A new measure of sexual intercourse
      using both the number of sexual partners and the number of coitions contained no
      missing data; adolescents classified as not having had interim sexual intercourse
      were free of infection at 3 months, whereas 32% of those who reported intercourse
      acquired an interim infection. CONCLUSIONS: These data suggest that high-risk
      urban adolescent women can accurately report whether they have engaged in vaginal
      intercourse. The validity of the report appears sensitive to the wording and
      content of the questions.

PMID- 9153736
TI  - Sexually transmitted diseases in men who have sex with men. Acquisition of
      gonorrhea and nongonococcal urethritis by fellatio and implications for STD/HIV
      prevention.
AB  - BACKGROUND AND OBJECTIVES: Despite trends toward safer sex practices in
      homosexually active men, some such people remain at high risk for acquiring
      sexually transmitted diseases (STD). This study was designed to assess behavioral
      and demographic determinants of STD acquisition in men who have sex with men
      (MSM), to guide prevention interventions. STUDY DESIGN: A cross-sectional medical
      record review was undertaken of MSM who attended an urban STD clinic from
      January, 1993 through December, 1994. Gonorrhea, chlamydial infection, Chlamydia
      negative nongonococcal urethritis (NGU), and newly documented human
      immunodeficiency virus (HIV) infection were analyzed in relation to demographic
      and behavioral variables. RESULTS: Among 1,253 MSM, 196 (15.6%) had nonchlamydial
      NGU, 105 (8.4%) had gonorrhea, 31 (2.5%) had chlamydial infection, and 162
      (12.9%) had known or newly documented HIV infection. Known HIV infection was an
      independent predictor of urethral gonorrhea (odds ratio [OR] 2.3, 95% confidence
      interval [CI95] 1.2-4.8). Oral insertive intercourse was independently associated
      with urethral gonorrhea (OR 4.4, CI95 1.4-13.4) and nonchlamydial NGU (OR 2.2,
      CI95 1.3-3.7), and receptive anal intercourse was associated with newly
      documented HIV infection (OR 2.6, CI95 1.3-4.9). Neither number of sex partners
      nor condom use was associated with any incident STD outcome, including new HIV
      infection. CONCLUSIONS: MSM who attend STD clinics represent a subgroup of
      homosexually active men who remain at high risk for STDs, including HIV
      infection. Fellatio, commonly thought to be a "safe" sexual practice, is an
      independent risk factor for urethral gonorrhea and nonchlamydial NGU. A history
      of consistent condom use or of few sex partners should not dissuade clinicians
      from performing screening tests for HIV and other STDs. Repeated STD screening
      and counseling about safer sex are indicated for many HIV-infected MSM.

PMID- 9153735
TI  - Antibody to Haemophilus ducreyi among trucking company workers in Kenya.
AB  - BACKGROUND AND OBJECTIVES: To determine the prevalence, correlates, and incidence
      of Haemophilus ducreyi antibodies, a cohort of East African trucking company
      employees was evaluated. STUDY DESIGN: Human immunodeficiency virus (HIV)-1
      seronegative men working in six trucking companies in Mombasa, Kenya, were
      evaluated with a questionnaire and serologic testing for antibodies to H. ducreyi
      and other sexually transmitted pathogens. Men who were initially H. ducreyi
      seronegative were retested at 1 year of follow-up. RESULTS: The H. ducreyi
      seroprevalence among 501 men at enrollment was 26.5%. Seropositivity was
      significantly associated with older age, married status, years of active sex
      life, number of sex partners in the past year, history of unprotected sex with a
      prostitute in the past year, and history of alcohol intake (all P values < 0.01).
      Occupational travel for more than 14 days per month was also significantly
      associated with H. ducreyi seropositivity (odds ratio [OR] 2.1, 95% confidence
      interval [CI] 1.3-3.2). Using multivariate analysis, H. ducreyi seropositivity
      was independently associated with age, married status, history of sex with a
      prostitute, and history of alcohol intake. Presence of H. ducreyi antibodies was
      significantly associated with seropositivity to the other major genital
      ulcerative pathogens, Treponema pallidum (OR 4.3, 95% CI 2.2-8.3), herpes simplex
      virus type 2 (OR 4.9, 95% CI 2.0-11.5), and Chlamydia trachomatis (OR 3.2, 95% CI
      1.5-6.9). These associations remained significant after adjusting for demographic
      and exposure variables. The incidence of seroconversion to H. ducreyi antibodies
      was 3.6 per 100 person years. CONCLUSIONS: Serologic evidence of H. ducreyi
      infection was common among male trucking company employees. H. ducreyi
      seropositivity is an objective marker of high-risk behavior and is associated
      with serologic evidence of other ulcerative sexually transmitted diseases.

PMID- 9153737
TI  - Safety of a nonoxynol-9 vaginal gel in Kenyan prostitutes. A randomized clinical
      trial.
AB  - OBJECTIVE: To evaluate the safety and toxicity of once-daily administration of
      Advantage-24 (Columbia Research Laboratories, Inc., Rockville Centre, NY), a
      vaginal gel containing 52.5 mg of nonoxynol-9 (N-9), including the effects of
      this gel on the vaginal and cervical epithelium. STUDY DESIGN: Randomized,
      placebo-controlled, double-blind crossover trial, with a 2-week product
      application period and a 2-week washout period. METHODS: Female sex workers in
      Mombasa, Kenya were randomized to one of two sequences, N-9 followed by placebo,
      or vice versa. Women were instructed to apply one applicator of N-9 or placebo
      gel vaginally once each day. During each of the two product periods, subjects
      were evaluated by questionnaire and physical examination, including colposcopy,
      after 7 and 14 days of product use. The primary outcome was genital epithelial
      disruption. RESULTS: Sixty subjects were randomized, of whom 52 (87%) had
      complete follow-up. There were four episodes of epithelial disruption, three of
      which occurred during the placebo period and one during the N-9 period. The
      estimated risk of epithelial disruption associated with N-9 use was 0.33 (95%
      confidence interval, 0.03-3.26). There was no increased frequency of other,
      nondisruptive epithelial lesions during N-9 use. CONCLUSIONS: No genital
      epithelial toxicity of N-9 vaginal gel was observed. This safety profile suggests
      that this N-9 product is appropriate for evaluation for human immunodeficiency
      virus type 1 prevention in a phase III efficacy trial.

PMID- 9153738
TI  - Mycoplasma genitalium in the cervices of Japanese women.
AB  - BACKGROUND: Mycoplasma genitalium is considered a cause of nongonococcal
      urethritis in men. This organism also is a cause of genital infections in women,
      and has been detected in women attending sexually transmitted disease clinics in
      the United Kingdom and Denmark, although its prevalence is unknown in Japanese
      women. GOALS: To determine the prevalence of M. genitalium in the cervices of
      women with cervicitis or adnexitis as well as in asymptomatic pregnant women in
      Japan. STUDY DESIGN: Two hundred women who attended obstetric and gynecologic
      clinics were recruited. Sixty-four women had cervicitis, 53 had adnexitis, and 3
      had both. Eighty pregnant women were asymptomatic for infection. Cervical swab
      specimens were examined for M. genitalium using a polymerase chain reaction-based
      assay. RESULTS: Five (7.8%) of 64 women with cervicitis and 3 (5.7%) of 53 women
      with adnexitis were positive for M. genitalium. After exclusion of Chlamydia
      positive women, 5 (8.8%) of 57 women with cervicitis, and 2 (4.1%) of 49 women
      with adnexitis were positive for M. genitalium. In none of 80 asymptomatic
      pregnant women, including a Chlamydia-positive woman, was M. genitalium detected.
      Overall, 7 (6.6%) of 106 women with Chlamydia-negative genital infections were
      positive for the M. genitalium. This prevalence was significantly greater than
      that in asymptomatic pregnant women (P < 0.05). CONCLUSIONS: A significantly
      greater prevalence of M. genitalium was demonstrated in Japanese women with
      Chlamydia-negative cervicitis or adnexitis, compared with that in asymptomatic
      pregnant women. This study suggests that M. genitalium may play a pathogenic role
      in a portion of cases with Chlamydia-negative genital infections.

PMID- 9153739
TI  - Partner notification to prevent pelvic inflammatory disease in women. Cost
      effectiveness of two strategies.
AB  - BACKGROUND AND OBJECTIVES: Partner notification is an important strategy for
      prevention of Chlamydia trachomatis infection and pelvic inflammatory disease
      (PID). PID can be prevented by early diagnosis and treatment of the female sex
      partners of men infected with C. trachomatis (strategy 1) and by preventing
      reinfection in women through diagnosis and treatment of their male sex partners
      (strategy 2). STUDY DESIGN: Using a decision model, the cost-effectiveness of
      strategies 1 and 2 was compared to no partner notification. Outcomes were
      measured by cases of PID prevented and net costs expended from a health care
      system perspective. RESULTS: In a hypothetical cohort of 1,000 male and 1,000
      female index patients, strategy 1 prevented 64 and strategy 2 prevented 20 cases
      of PID. Strategy 1 saved $247,000 and strategy 2 saved $33,000 over no partner
      notification. Sensitivity analysis showed that strategy 1 was cost-effective
      across a wide range of assumptions. Strategy 2 was cost-effective at baseline,
      but its cost-saving ability was subject to changes in the model. CONCLUSION:
      Partner notification of both male and female index patients is a cost-effective
      public health strategy for prevention of PID. In most settings, both strategies
      can and should be implemented.

PMID- 9153740
TI  - Factors associated with human papillomavirus infection detected by polymerase
      chain reaction among urban Canadian aboriginal and non-aboriginal women.
AB  - OBJECTIVES: To determine the prevalence and correlates of human papillomavirus
      (HPV) infection among women attending an ethnically mixed, predominantly low
      income, inner-city primary care clinic. STUDY DESIGN: Cross-sectional survey (N =
      1,477). Demographic, behavioral, and reproductive history data were collected by
      questionnaire. Cervical swabs were analyzed for gonorrhea and chlamydial
      infections, abnormal cytology, and HPV infection assessed by PCR followed by
      hybridization for types 6, 11, 16, 18, 31, 33, and 35. RESULTS: Human
      papillomavirus was detected in 33% of specimens, with no significant difference
      between Aboriginal (AB) and non-Aboriginal women. Adjusting for AB status, HPV
      infection was associated with marital status, condom use, number of sexual
      partners (last year and lifetime), age at first sexual intercourse, a history of
      sexual abuse, and current abnormal Papanicolaou (Pap) smear. In multivariate
      analyses excluding abnormal Pap smear as an independent variable, marital status
      and the number of lifetime sexual partners were found to be significant
      independent predictors of HPV infection. Comparing individuals with 20+ lifetime
      sexual partners and those with 1 or fewer partners, the odds ratio (OR) for HPV
      infection was 1.90 (95% confidence interval [CI] 1.66-2.17) among AB women and
      1.54 among non-AB women (95% CI 1.36-1.73). The OR for infection with HPV types 6
      and 11 was 1.39 (95% CI 1.22-1.58), whereas for the high oncogenic risk types of
      16, 18, 31, 33, and 35, the OR was 1.82 (95% CI 1.65-2.01). CONCLUSIONS: No
      differences were found between AB and non-AB women in the detection of HPV DNA,
      despite the higher risk for cervical cancer and the prevalence of recognized
      behavioral and reproductive risk factors among AB women. This study also
      indicates that the association of sexual activity with HPV infection holds true
      for both high- and low-oncogenic HPV types.

PMID- 9153743
TI  - BSE: SEAC statement on maternal transmission.

PMID- 9153742
TI  - New paradigms for sexually transmitted diseases surveillance and field studies.

PMID- 9153741
TI  - The promise of integrated representative surveys about sexually transmitted
      diseases and behavior.
AB  - BACKGROUND: It has been difficult to conduct representative surveys measuring
      both sexually transmitted disease prevalence and behavioral data. This article
      reviews the literature, describes a recent pretest of the feasibility of
      integrated surveys, and discusses the potential implications. METHODS: Several
      national surveys are reviewed, including the National Health and Nutrition
      Examination Surveys, National Health and Social Life Survey, and National Survey
      of Adolescent Males. The 1994 pretest of the National Survey of Adolescent Males
      collected urine specimens of male respondents, which were tested for Chlamydia
      trachomatis using ligase and polymerase chain reaction tests. RESULTS: There have
      not been any prior national surveys that collect clinical measures of STD
      infection and detailed behavioral data. In the pretest, 85% of the eligible
      interview respondents provided a urine specimen. Of those tested, 6% were
      positive for C. trachomatis. CONCLUSIONS: Combining behavioral surveys with
      collection of urine specimens for STD testing in representative samples is
      feasible. However, STD testing adds new operational and ethical challenges to the
      conduct of household surveys.

PMID- 9153744
TI  - Verification of the identity of bovine semen using DNA microsatellite markers.
AB  - Over the past 30 years cattle have been identified by blood typing, but recently
      the use of DNA markers has provided a more precise method of identifying
      individuals and verifying their parentage. This article describes the use of
      microsatellite-based DNA markers for confirming the identity of semen, as part of
      the evidence presented in a legal dispute. Two panels of markers and two methods
      for identifying allelic variation are compared; for both approaches the
      likelihood of finding two Charolais individuals with the same genotype was less
      than one in a million. Animals can therefore be identified conclusively from DNA
      samples, a technique which could be of use when their identity is in dispute.

PMID- 9153745
TI  - Sterilisation of surgical instruments with formaldehyde gas.
AB  - Haemostatic forceps contaminated with Pseudomonas aeruginosa, Staphylococcus
      aureus, Bacillus cereus and Aspergillus flavus were exposed to formaldehyde gas
      for up to 48 hours at different temperatures and relative humidities. After 24
      hours at 22 to 24 degrees C and a relative humidity of 73 per cent they were
      sterilised reliably and completely.

PMID- 9153746
TI  - Treatment of a keratoma in a Clydesdale horse.
AB  - A keratoma was diagnosed in a six-year-old Clydesdale gelding with recurrent 'pus
      in the foot'. The keratoma was excised through an inverted 'V' dorsal wall hoof
      resection up to 2 cm distal to the coronary band, the foot was bandaged and shod,
      and the horse treated with antibiotics and phenylbutazone. The dorsal hoof wall
      regrew completely and the horse gradually returned to full work.

PMID- 9153747
TI  - Avian tuberculosis caused by Mycobacterium avium serotype 3 in captive wildfowl.

PMID- 9153748
TI  - Comparison of catgut and polyglactin 910 for uterine sutures during bovine
      caesarean sections.

PMID- 9153749
TI  - Re-emergence of a stunting syndrome in broiler chickens.

PMID- 9153750
TI  - PCR-based diagnosis of feline infectious peritonitis.

PMID- 9153751
TI  - Suspected allergic reaction to penicillamine in mute swans.

PMID- 9153752
TI  - Review: an overview of the Saccharomyces cerevisiae microtubule and microfilament
      cytoskeleton.

PMID- 9153753
TI  - The branched-chain amino acid permease gene of Saccharomyces cerevisiae, BAP2,
      encodes the high-affinity leucine permease (S1).
AB  - The amino acid leucine has been shown previously to be transported into a yeast
      cell by at least three permeases: the general amino acid permease, a high
      affinity permease (S1) and a low-affinity permease (S2). We isolated the gene
      BAP2 as a multicopy suppressor of the YPD- phenotype of aat1leu2 yeast. BAP2 has
      been identified previously as encoding an amino acid permease which transports
      branched-chain amino acids. In order to align the genetic and biochemical studies
      of leucine uptake we completed a detailed kinetic analysis of yeast strains in
      which the BAP2 gene was disrupted and compared this to the kinetics of uptake of
      the parental strain. We demonstrate that BAP2 encodes the high-affinity leucine
      permease previously called S1.

PMID- 9153754
TI  - Meiotic inheritance of functional Gal80S gene product in Saccharomyces
      cerevisiae.
AB  - Transcription factors inherited during meiosis play a crucial role directing
      subsequent gene activity. Factors of maternal origin have been shown to influence
      the pattern of early zygotic transcription during Drosophila and Xenopus
      embryogenesis. Nevertheless, little is known regarding the meiotic inheritance of
      the vast majority of transcription factors. In the case of yeast meiosis, for
      example, it is not yet known whether any of the multitude of transcription
      factors expressed in the diploid are transmitted to haploid spores in functional
      form. Here we use a GAL1-STE4 reporter whose activity is detectable in single
      living cells to identify a transcription factor inherited during sporulation in
      Saccharomyces cerevisiae. We show that functional Gal80S repressor is meiotically
      inherited at levels reflecting its expression in the diploid parent.

PMID- 9153755
TI  - A conditional sterol esterification defect in yeast having either a sec1 or sec5
      mutation in the secretory pathway.
AB  - Two temperature-conditional secretory mutations, sec1 and sec5, cause the
      accumulation of post-Golgi vesicles when strains containing these mutations are
      grown at 37 degrees C. In addition to accumulating vesicles, the mutants do not
      esterify free sterol on rich media at the restrictive temperature. It is the high
      level of inositol in the media that causes this condition in the yeast
      Saccharomyces cerevisiae, not a defective steryl ester synthase or lack of
      substrates. When strains containing the sec1 or sec5 mutation were transformed
      separately with a plasmid carrying SEC1 and SEC5, the esterification and
      secretory defects were alleviated. Double mutants containing sec6, sec14 or sec18
      with either a sec1 or sec5 mutation have normal esterification levels. Strains
      with suppressor mutations were isolated that grew at 37 degrees C, esterified
      sterols and had diminished accumulation of vesicles, when grown at the
      restrictive temperature on defined media with additional inositol. Electron
      microscopy was used to examine vesicle accumulation, the number of lipid
      droplets, and to further characterize the esterification defect. When grown at 37
      degrees C on defined medium, the strains with sec5 or sec1 accumulated the usual
      secretory vesicles, but when grown under similar conditions with elevated levels
      of inositol, accumulated an additional vesicular-like body.

PMID- 9153756
TI  - Isolation of a Schizosaccharomyces pombe gene which in high copy confers
      resistance to the nucleoside analogue 5-azacytidine.
AB  - Treatment of Schizosaccharomyces pombe with the C5 DNA methyltransferase
      (C5Mtase) inhibitor 5-azacytidine (5-azaC) has previously been shown to induce G2
      checkpoint-dependent cell cycle arrest. S. pombe strains defective in both the
      checkpoint control pathways and in DNA repair processes are sensitive to 5-azaC.
      Here we describe the isolation of azr1+, as a multi-copy suppressor of the 5-azaC
      sensitivity of G2 checkpoint and DNA repair-deficient strains. azr1+ encodes a
      putative 25 kDa protein with limited homology to a Saccharomyces cerevisiae open
      reading frame of unknown function. The azr1+ gene is not essential and the null
      mutant shows no alteration in either DNA repair or checkpoint properties. We also
      report the sequence of the putative fission yeast cytidine deaminase gene,
      designated pcd1+, which lies immediately adjacent to azr1+ but which plays only a
      moderate role in suppression of 5-azaC sensitivity.

PMID- 9153757
TI  - Analysis of 21.7 kb DNA sequence from the left arm of chromosome VII reveals 11
      open reading frames: two correspond to new genes.
AB  - The DNA sequence of a fragment of 21731 bp (nucleotides 87408 to 109138) located
      on the left arm of chromosome VII from Saccharomyces cerevisiae S288C has been
      determined using a random cloning strategy followed by an oligonucleotide
      directed sequencing. This fragment contains eight complete genes previously
      sequenced (CLG1, SKI8, VAM7, YPT32, MIG2, SIP2, SPT16 and CHC1), the 5' part of
      POX1 and two other complete unidentified open reading frames of more than 100
      amino acids.

PMID- 9153758
TI  - Sequence and analysis of a 36.2 kb fragment from the right arm of yeast
      chromosome XV reveals 19 open reading frames including SNF2 (5' end), CPA1,
      SLY41, a putative transport ATPase, a putative ribosomal protein and an SNF2
      homologue.
AB  - The complete sequence of a 36 196 bp DNA segment located on the right arm of
      chromosome XV of Saccharomyces cerevisiae has been determined and analysed. The
      sequence includes the 5' coding region of the SNF2 gene, the CPA1 leader peptide
      sequence and 17 open reading frames (ORFs) of at least 100 amino acids. Two of
      these correspond to previously known genes (CPA1, SLY41), whereas 15 correspond
      to new genes. The putative translation products of three ORFs show significant
      similarity with known proteins: one is a putative transport ATPase, another
      appears to be a ribosomal protein, and the third is an Snf2p homologue.

PMID- 9153759
TI  - Sequencing analysis of a 36.8 kb fragment of yeast chromosome XV reveals 26 open
      reading frames including SEC63, CDC31, SUG2, GCD1, RBL2, PNT1, PAC1 and VPH1.
AB  - The complete sequence of a 36775 bp DNA segment located on the right arm of
      chromosome XV of Saccharomyces cerevisiae has been determined and analysed. The
      sequence encodes 26 open reading frames of at least 100 amino acids. Eight of
      these correspond to known genes, whereas 18 correspond to new genes.

PMID- 9153760
TI  - The RAD29 gene: map position on the right arm of chromosome II.

PMID- 9153761
TI  - Current awareness on yeast.

PMID- 9153762
TI  - Spontaneous maturation in Bufo arenarum oocytes: participation of protein kinase
      C.
AB  - Although progesterone is the maturation inducer in amphibians, it has been
      demonstrated that in Bufo arenarum oocytes resumed meiosis with no need of
      exogenous hormonal stimulus if derived of their enveloping follicle cells. This
      phenomenon, called spontaneous maturation, is quite rare in amphibians. In B.
      arenarum, spontaneous maturation took place only in oocytes obtained during the
      reproductive period (spring-summer). During this period the oocytes also
      demonstrated a respiratory activity characteristic of mature oocytes.
      Interestingly, full-grown B. arenarum oocytes always responded to progesterone
      regardless of the season in which they were obtained and of their respiratory
      activity. The disposition of oocytes competent or not competent to mature
      spontaneously provides a useful system for the study of molecular mechanisms
      involved in the maturation process. The data presented here indicate that the
      activation of protein kinase C (PKC) induces germinal vesicle breakdown (GVBD) in
      denuded oocytes unable to mature spontaneously (winter oocytes) and is involved
      in the in vitro spontaneous maturation of B. arenarum full-grown oocytes. The
      inhibition of PKC by 1-(5-isoquinolynyl-sulphonyl-2-methyl-piperazine (H-7)
      impeded spontaneous maturation in a dose-dependent manner, thus supporting the
      participation of the PKC pathway during this process. Interestingly phorbol 12
      myristate-13-acetate (PMA)-induced GVBD is inhibited by the incubation of the
      oocytes in dibutyryl cAMP (dbcAMP), indicating that both pathways, PKC and
      protein kinase A (PKA), are related at a certain point. However, spontaneous GVBD
      is less sensitive than PMA-induced GVBD to dbcAMP. This fact would support the
      suggestion that in spontaneous GVBD mechanisms different from activation of PKC
      are at work.

PMID- 9153763
TI  - Unprotected freezing of human spermatozoa exerts a detrimental effect on their
      oocyte activating capacity and chromosome integrity.
AB  - The influence of unprotected freezing of mammalian spermatozoa on their oocyte
      activating capacity and chromosome integrity is unknown. However, this type of
      sperm treatment has been used in assisted reproduction by intracytoplasmic sperm
      injection in cattle and humans. The mouse oocyte injection test was used to
      analyse the influence of unprotected freezing of human spermatozoa on their
      reproductive characteristics. Mouse oocytes were microinjected with intact human
      spermatozoa or spermatozoa treated with two cycles of unprotected freeze-thawing.
      Oocytes surviving the injection were either cultured without further treatment or
      exposed to ethanol solution to induce parthenogenetic activation. Both injected
      and activated oocytes were used for sperm chromosome analysis. The results
      revealed a significant reduction in oocyte activating capacity and a tenfold
      increase in the incidence of structural chromosomal abnormalities in human
      spermatozoa treated by unprotected freezing. We conclude that unprotected
      freezing of human spermatozoa has a detrimental effect on their reproductive
      characteristics. Our data also provide a new perspective on the stability of
      mammalian spermatozoa to physical factors and demonstrate the importance of
      detailed analysis of the stability of sperm structures for successful development
      of new approaches in assisted reproduction.

PMID- 9153765
TI  - Tolerance of oocyte plasma membrane to electric current changes after
      fertilisation.
AB  - The tolerance of the oocyte plasma membrane (oolemma) to electrical pulses (TEP)
      was investigated for oocytes, zygotes, and embryos at the early and late 2-cell
      stage. The oocyte survival rate after two electrical pulses (1.4 kV/cm for 640
      microns each) was used as an indicator of the TEP of the oolemma. Survival rate
      of mid-pronuclear zygotes (94.3% +/- 2.3%) was significantly (p < 0.05) higher
      than that of recently ovulated (2.1% +/- 1.9%) and in vivo aged (25.1% +/- 2.6%)
      oocytes; survival rate of in vivo aged oocytes was also significantly higher than
      that of recently ovulated oocytes. Soon after fertilisation, the survival rate of
      the oocytes markedly increased, up to 94% at the mid-pronuclear stage. Survival
      rate dropped thereafter. These results suggest that the characteristics of the
      oocyte plasma membrane (oolemma) change after fertilisation.

PMID- 9153764
TI  - Comparison of methods for activating mouse oocytes for spermatid nucleus
      transfer.
AB  - In the mouse, mature oocytes injected with prespermatozoal cell nuclei remain
      unactivated. Additional stimulation is needed to trigger oocyte activation
      leading to embryo development. We compared various electrical stimulations,
      treatment with cycloheximide alone or in combination with electrical stimulation,
      and injection of sperm-borne oocyte-activating factor (oscillogen) in terms of
      their oocyte activation and embryo development rates. Of all the treatments
      tested, a single electrical pulse (1.0 kV/ cm, 128 microns) was the simplest, yet
      very effective, in allowing the development of the oocytes injected with
      spermatid nuclei.

PMID- 9153767
TI  - Antral follicles confer developmental competence on oocytes.

PMID- 9153766
TI  - Combined use of proacrosin immunocytochemistry and autosomal DNA in situ
      hybridisation for evaluation of human ejaculated germ cells.
AB  - The recently reported human pregnancies and births after fertilising oocytes with
      round spermatids recovered from the ejaculate of men with non-obstructive
      azoospermia have underscored the need for a more accurate evaluation of the
      nuclear and cytoplasmic maturation status of ejaculated germ cells. In this study
      we describe our first experience with a method combining the immunocytochemical
      visualisation of proacrosin with autosomal DNA fluorescence in situ hybridisation
      (FISH) to assess ejaculated germ cells from patients with a spermiogenesis
      defect. The proacrosin immunoreactivity, analysed with the use of the monoclonal
      antibody 4D4, has been detected in cells of round spermatid size presenting a
      haploid FISH figure as well as in larger cells whose ploidy corresponds to
      primary and secondary spermatocytes. These observations are in agreement with
      previously published results obtained, with the use of the same antibody, by
      immunocytochemical analysis of histological sections of testicular tissue. All
      the cells of round spermatid size possessing proacrosin immunoreactivity were
      found to be haploid by FISH. On the other hand, some of the haploid cells of
      round spermatid size did not possess proacrosin immunoreactivity. The structural
      pattern of proacrosin immunoreactivity was highly variable both in spermatids and
      in younger spermatogenic cells. These data show that cell size is the main
      criterion to be used for the identification of ejaculated round spermatids,
      whereas the presence of the developing acrosome represents only an auxiliary
      criterion. The scoring of acrosomal development in ejaculated spermatids may be
      useful as part of pre-treatment diagnosis before the inclusion of infertile
      couples in a spermatid conception programme.

PMID- 9153768
TI  - Control of ovarian innervation.

PMID- 9153769
TI  - Gonadotropin suppression of apoptosis in follicle somatic cells.

PMID- 9153770
TI  - Influence of granulosa cells and of different somatic cell types on mammalian
      oocyte development in vitro.

PMID- 9153771
TI  - Participation of nerve growth factor in the regulation of ovarian function.

PMID- 9153772
TI  - Endocrine and paracrine regulation of cumulus expansion.

PMID- 9153773
TI  - Oocyte-secreted factors regulate granulosa cell steroidogenesis.

PMID- 9153774
TI  - Intra-ovarian regulation of oocyte developmental competence in cattle.

PMID- 9153775
TI  - Follicular dominance and oocyte maturation.

PMID- 9153776
TI  - Cumulus expansion initiates physical and developmental autonomy of the oocyte.

PMID- 9153777
TI  - Influence of vasoactive intestinal peptide (VIP), atrial natriuretic peptide
      (ANP) and insulin-like growth factor-I (IGF-I) on in vitro maturation of
      prepubertal and adult sheep oocytes.

PMID- 9153778
TI  - Role of stem cell factor in somatic-germ cell interactions during prenatal
      oogenesis.

PMID- 9153779
TI  - Report of the European DNA profiling group (EDNAP): an investigation of the
      complex STR loci D21S11 and HUMFIBRA (FGA).
AB  - This paper describes a collaborative exercise which was intended to demonstrate
      whether uniformity of DNA profiling results could be achieved between European
      laboratories using two complex short tandem repeat (STR) loci. The loci D21S11
      and HUMFIBRA (FGA) were chosen because they are commonly used by different
      European laboratories. D21S11 has approximately 14 common alleles (f > 0.001),
      whereas HUMFIBRA has 19 common alleles. Laboratories were asked to test seven
      blood stains, one of which was a known control, and to report the results to the
      coordinating laboratory. The exercise demonstrated that complex STRs were
      amenable to standardisation.

PMID- 9153780
TI  - Death attributed to the toxic interaction of triazolam, amitriptyline and other
      psychotropic drugs.
AB  - A 71-year-old man was found dead in a car into which exhaust fumes had been
      introduced. His wife who was in the same car recovered consciousness following
      hospitalization. She claimed that they had both attempted suicide by taking a
      large number of sleeping pills. Autopsy revealed no significant external injuries
      or medical disorders that would have led to the husband's death. The
      concentrations of alcohol and carbon-monoxide hemoglobin in his whole blood were
      0.26 mg/ml and < 10%, respectively. Therefore, poisoning by carbon monoxide from
      the exhaust fumes was ruled out, and further toxicological examinations were
      undertaken. Triazolam, pentobarbital, amitriptyline and bromazepam were all
      detected in the tissues of the victim; whole blood concentrations were 45.60,
      386.4, 521.2 and 166.7 ng/g, respectively. Triazolam (7.350 ng/g) and
      pentobarbital (288.2 ng/g) were also detected in the whole blood of the wife,
      collected 17 h after admission to hospital. When evaluating these results in the
      light of existing literature, we concluded that the victim and his wife had
      indeed attempted suicide by taking triazolam and pentobarbital. However, only the
      man had died of triazolam poisoning due to its apparently lethal combination with
      amitriptyline and other psychotropic drugs which had been prescribed to treat his
      depression.

PMID- 9153781
TI  - Tramadol distribution in four postmortem cases.
AB  - Four postmortem cases are reported in which the analgesic drug tramadol was
      identified. Tramadol is an alkaline extractable drug and elutes from a HP-5
      column without the need for derivatization. Two metabolites of tramadol, N
      desmethyl and O-desmethyl tramadol were also identified. Heart blood
      concentrations of tramadol in the four cases ranged from 0.17 to 4.4 mg/l. Tissue
      distribution of tramadol in the four cases failed to identify a sequestration
      site. None of the deaths reported were attributed to tramadol intoxication.

PMID- 9153782
TI  - Simultaneous solid-phase extraction on C18 cartridges of opiates and cocainics
      for an improved quantitation in human hair by GC-MS: one year of forensic
      applications.
AB  - We have developed a new solid-phase extraction (SPE) on C18 cartridges which
      allows a very simple protocol of manipulation and a single elution of opiates and
      cocainics from human hair samples. The method involved decontamination in a
      phosphate buffer and dichloromethane, pulverization in a ball mill, addition of
      deuterated internal standards, heated acid hydrolysis and SPE. Quantitation
      utilized gas chromatography and mass spectrometry. Between days precise study
      gave relative standard deviations always inferior to 8.9% for each compound at 4
      ng/mg (except methylecgonine ester = 15.7%). Accuracy was tested using a t
      statistic versus a reference material from the NIST. Limits of detection were
      calculated from an analysis of the blanks which contained between 0.12 and 0.28
      ng/mg for each drug. The method was applied in forensic cases for 1 year of
      toxicological activity. Among the 108 analyses performed, 30 were positive for
      cocaine and 33 for opiates. Concentrations were in the range 0.9-242.0 ng/mg
      (cocaine), 0.3-71.3 ng/mg (benzoylecgonine), 0.0-9.8 ng/mg (methylecgonine
      ester), 0.0-2.9 ng/mg (cocaethylene), 0.1-11.5 ng/mg (codeine), 0.4-44.6 ng/mg
      (morphine) and 0.7-131.2 ng/mg (6-acetylmorphine). Ratios of the metabolites to
      parent drugs were proposed to avoid risk of external contamination.

PMID- 9153783
TI  - Expression of ubiquitin protein in each organ at death from hypothermia.
AB  - To examine the expression of heat shock protein (hsp) in each organ on autopsy in
      11 deaths from hypothermia, we performed immunological staining of specimens from
      each organ using an antibody to hsp, ubiquitin (Ub). Staining of the liver,
      kidneys, lungs and pancreas revealed a high level of Ub expression in the
      cytoplasm and nuclei. However, staining of the same specimens of all controls
      revealed no Ub expression in the cytoplasm or nuclei. This finding suggests that
      cells are affected by stress even at a low temperature, and may be important in
      clarifying the cellular kinetics in death from hypothermia.

PMID- 9153784
TI  - Methanol elimination in non-alcoholics: inter- and intraindividual variation.
AB  - Five male subjects aged between 25 and 40 years were given methanol at a dose of
      10 mg/kg, once orally and once intravenously, while the enzyme systems
      responsible for methanol oxidation were blocked by ethanol. The study assessed
      the duration of inhibition of methanol oxidation in relation to the blood ethanol
      concentration, and the elimination of methanol not influenced by ethanol.
      Methanol elimination was found to begin at a blood ethanol concentration of 0.04
      0.13 g/kg. Elimination constants of 0.406-0.267 h-1 with corresponding half-lives
      of 1.71-2.60 h were established for methanol not influenced by ethanol. When data
      from a previous study using an identical protocol for parenteral administration
      were included, making the total number of subjects nine, the mean elimination
      constant was found to be 0.298 +/- 0.470 h-1 and the mean half-life 2.37 +/-
      0.357 h, distribution being normal. No evidence of any differences in methanol
      elimination kinetics between alcoholics and non-alcoholics or of a significant
      influence of the route of administration was found. The extent of intraindividual
      variation in methanol elimination as indicated by the difference in each subject
      between the values established, expressed as a percentage of the corresponding
      mean values, was found to be 3-25%, which is comparable to the magnitude of
      intraindividual variation in the rate of ethanol elimination.

PMID- 9153786
TI  - The GCMS analysis of tranylcypromine (Parnate) in a suspected overdose.
AB  - A fatal overdose involving tranylcypromine (Parnate) where blood, urine and
      tissues were quantitated using a pentafluoroproprionic anhydride (PFPA)
      derivative and gas-chromatography/mass spectroscopy (GCMS). The samples were re
      quantified over several weeks demonstrating a significant loss of drug in tissues
      but not blood or urine specimens. The urine was positive for methamphetamine
      which has been a suspected metabolite.

PMID- 9153785
TI  - Proteolysis of ankyrin and Na+/K(+)-ATPase in postmortem rat brain: is calpain
      involved?
AB  - Ankyrin links the fodrin-based cytoskeleton to membrane proteins such as Na+/K(+)
      ATPase, thereby maintaining cellular integrity. Immunoblotting by antibody raised
      against erythrocyte ankyrin demonstrated the proteolysis of ankyrin, which was
      highly correlated with postmortem interval (0-24 h). Proteolysis in the
      postmortem brain generated the 160-kDa fragment with an identical size as the
      fragment formed after in vitro proteolysis by calpain. Although microM Ca2+
      induced the proteolysis in the homogenate, the presence of mu-calpain was not
      demonstrated by immunoblotting using the antibody that reacts with large subunits
      both of mu- and m-calpains. Na+/K(+)-ATPase was also proteolyzed in the
      postmortem brain.

PMID- 9153787
TI  - The HumD21S11 system of short tandem repeat DNA polymorphisms in Japanese and
      Chinese.
AB  - HumD21S11 is a short tandem repeat DNA polymorphic system with a complex basic
      structure of (TCTA)4-6 (TCTG)5-6 (TCTA)3 TA (TCTA)3 TCA (TCTA)2 TCCA TA (TCTA)n.
      Using the allelic ladder prepared by us, the distribution of alleles among
      Japanese and Chinese was investigated, and four new alleles 28.2, 34, 35.2, and
      36.2, were discovered. DNA sequencing was performed on the newly found alleles as
      well as on family samples and led to the discovery of different gene structures
      within alleles 28 and 32. Forensic materials, including hairs and seminal stains,
      were tested in parallel with blood samples from the same individual and were
      successfully typed for D21S11.

PMID- 9153788
TI  - Fatal overdose of clozapine.
AB  - An ingestion of an unknown quantity of Leponex (clozapine) tablets in a suicide
      is described. Although clozapine is known for over 30 years now, relatively few
      cases of intoxications due to clozapine overdose have been reported. The authors
      report a new and quick method to analyze and determine the clozapine and N
      desmethylclozapine concentration in body fluids. The analytes and an internal
      standard (zolpidem) were extracted from alkalinized samples into ethyl acetate
      before GC/NPD analysis. The proposed method resulted in a rapid procedure most
      useful in cases of deliberate poisoning with the neuroleptic drug Leponex.

PMID- 9153789
TI  - A comparison of ethanol concentrations in the occipital lobe and cerebellum.
AB  - While many publications have addressed the issue of ethanol concentration in
      brain tissue as a better indicator of impairment than blood alcohol concentration
      (BAC), very few have looked at the regional distribution of ethanol in the brain
      and its possible significance in postmortem sampling. This paper reports on the
      analysis of occipital pole and cerebellar hemisphere for ethanol in 25/brain
      samples obtained at autopsy from the brain collection of the National Institutes
      of Mental Health/Stanley Foundation. When available, these concentrations were
      compared to BAC. The average ratio of occipital lobe alcohol concentration (OAC)
      to BAC for cases which also had blood samples (18/24) was 0.9, SD = 0.5, with a
      range of 0-1.8; the average ratio of cerebellar alcohol concentration (CAC) to
      BAC for these cases was 0.6, SD = 0.4, range = 0-1.2. When only those cases with
      a BAC > or = 0.04 g/dl (14/18 cases) were considered, the average OAC/BAC and
      CAC/BAC ratios were 0.8 (SD = 0.4) and 0.7 (SD = 0.4), respectively. These
      distribution ratios are well within the ranges reported by other authors and do
      not significantly differ from each other. The cortical brain region available or
      selected for postmortem ethanol analysis is probably not critical.

PMID- 9153790
TI  - A modified method for examining the cardiac conduction system.
AB  - A revised technique is described in which the sino-atrial node, the atrio
      ventricular node and the distal part of the His bundle and the bundle brances of
      the cardiac conduction system are demonstrated in longitudinal sections through
      cutting of 4-5 blocks. The longitudinal sectioning allows observation of
      continuity between different components of the cardiac conduction tissue. This
      method reduces the workload and hopefully encourages the pathologist to make the
      examination of the cardiac conduction system a part of the routine procedure.

PMID- 9153791
TI  - Concerning the paper by Poklis et al., entitled: 'Gas chromatographic procedures
      for determination of ethanol in postmortem blood using t-butanol and methyl ethyl
      ketone as internal standards' (Forensic Sci. Int., 33 (1996)[correction of 1987]
      31-38)

PMID- 9153792
TI  - Changes in the DNA profile caused by toxic substances?

PMID- 9153793
TI  - Loneliness and the effects of life changes.
AB  - In this study, factor analysis was used to examine whether men and women
      experience loneliness differently and how marital status affects the experience
      of loneliness (especially if the marriage is terminated). The experiences of
      chronic and situational or event-related loneliness are also compared. Finally,
      the study is also an investigation of the social stigma that causes people to
      refuse to admit their loneliness. As a result of this stigma, when questioned for
      research purposes, individuals usually report a recall past loneliness rather
      than a current or ongoing experience. In the present study, the difference
      between loneliness recalled and loneliness experienced at the time of questioning
      is investigated.

PMID- 9153794
TI  - Did the APA misrepresent the scientific literature to courts in support of
      homosexual custody?
AB  - In 1994, American Psychological Association amicus briefs informed two state
      Supreme Courts that (a) homosexual parents are not more apt to have homosexual
      children; (b) lesbians "score significantly higher than heterosexual parents" on
      a measure of parental effectiveness; and (c) no differences between the children
      raised by homosexuals and nonhomosexuals had been found "regardless of the
      geographic region within the United States where the children were raised." In
      fact, the evidence from these briefs shows to the contrary that (a) homosexual
      parents are more apt to have homosexual children; (b) the findings on parental
      effectiveness consisted of 15 fathers being less verbal than 45 mothers; and (c)
      the finding of no differences between homosexually and heterosexually raised
      children consisted of investigators visiting 11 states to test 89 offspring of 83
      lesbian vs. 81 children of 69 nonlesbian volunteers. The APA's support for gay
      rights in these briefs may have violated its own ethical principles that
      "psychologists base their statements on scientifically acceptable psychological
      findings and techniques with full recognition of the limits and uncertainties of
      such evidence" and that psychologists must "provide thorough discussion of the
      limitations of their data, especially where their work touches on social policy"
      (APA, 1981).

PMID- 9153795
TI  - Using metaphors to assess anticipatory perceptions of personal death.
AB  - The Revised Death Fantasy Scale (RDFS) is an 18-item measure based on metaphors
      of personal death. It was constructed to assess psychological aspects of
      contemplating personal death, at levels of awareness less conscious than those
      tapped by conventional self-report measures. It contains two subscales: Positive
      Metaphors and Negative Metaphors. In several studies the RDFS has shown evidence
      of reliability and validity. The scale may be potentially useful in health
      related research and in the training and support of individuals whose work is
      related to death and dying.

PMID- 9153796
TI  - Munchausen syndrome/Munchausen syndrome by proxy.
AB  - Munchausen syndrome (MS) is characterized by patients' chronic and relentless
      pursuit of medical treatment for combinations of symptoms of consciously self
      inflicted injury and falsely reported symptomatology. MS patients are adults, as
      are perpetrators of Munchausen syndrome by proxy (MSBP). MSBP is an unusual form
      of child abuse in which a parent, usually the mother, brings a child for medical
      attention with symptoms falsified or directly induced by the mother. Most reports
      of MSBP have been of a few cases appearing in medical and pediatric literature.
      Motivation in both disorders is unclear, and diagnosis and treatment present
      difficult problems that require more research.

PMID- 9153797
TI  - NMR relaxation data of water proton in normal tissues.
AB  - The spin lattice relaxation time (T1) and spin spin relaxation time (T2) of water
      protons of normal human and animal tissues are archived to up-date those already
      published. The mechanisms for water proton relaxation times of tissues are
      reviewed with reference to water content, paramagnetic ion, protein dynamics
      content and organ weight.

PMID- 9153798
TI  - Mechanism that regulates nitric oxide production by lipopolysaccharide-stimulated
      rat Kupffer cells.
AB  - Mechanism that regulates nitric oxide (NO) production by stimulated Kupffer cells
      was studied. Lipopolysaccharide (LPS) stimulated NO production by primary
      cultured Kupffer cells in a time- and dose-dependent manner. Twenty-four h after
      incubation with 1 microgram/ml of LPS, the nitrite concentration in the culture
      medium increased from 2.87 +/- 1.4 to 73.6 +/- 6.9 nmol/ml. NO production started
      to increase around 6 h after adding LPS and reached a maximum within 24 h. NO
      production was inhibited by 0.3 mM of NG-monomethyl-L-arginine and was reversed
      by adding 3 mM of L-arginine. When incubated with 1 microgram/ml of LPS for 24 h,
      NO synthase activity in Kupffer cells increased from 0.164 +/- 0.035 to 3.16 +/-
      0.11 nmol/min/mg protein. Dexamethasone and prednisolone significantly inhibited
      the induction of NO synthase and NO production in Kupffer cells. Expression of
      mRNA for inducible type of NO synthase (iNOS) started to increase around 4 h
      after adding LPS (1 microgram/ml) and reached a maximum by about 20 h. The
      enhanced expression of iNOS mRNA was also suppressed by 1 microM dexamethasone.
      On the other hand, calcium ionophore A23187 significantly enhanced the induction
      of NO synthase and iNOS mRNA expression in LPS-stimulated Kupffer cells. In
      addition, a tyrosine kinase inhibitor, genistein (100 microM), significantly
      inhibited NO production by LPS-stimulated Kupffer cells. Neither phorbol 12
      myristate 13-acetate, dibutyryl cAMP, indomethacin nor a protein kinase C
      inhibitor H-7 affected NO production by Kupffer cells. These results suggested
      that iNOS mRNA expression, NO synthase activity and NO production increased in
      LPS-stimulated Kupffer cells by a glucocorticoid-inhibitable mechanism and that
      Ca2+ and tyrosine phosphorylation might play important roles in LPS-dependent
      induction of NO synthase.

PMID- 9153799
TI  - Electrolyte metabolic changes in rats during and after exposure to hypokinesia.
AB  - The objective of this study was to determine fluid-electrolyte changes in male
      Wistar rats during 90 days of hypokinesia (decreased motor activity) and 15 days
      posthypokinesia. The animals were divided into two groups: rats subjected to
      hypokinesia served as experimental animals and rats placed under vivarium
      conditions served as control animals. The hypokinetic effect was carried out by
      keeping the experimental rats in small individual cages which restricted all
      their movements without hindering food and water intake. Determination was made
      of body weight, fluid consumed and eliminated in urine, sodium and potassium
      excretion in urine, concentrations of sodium and potassium in urine, the
      hematocrit level and water content in blood, and plasma concentration of sodium
      and potassium. During the experimental period body weight, water intake, urinary
      sodium and potassium content, and water content in blood decreased significantly,
      while electrolyte excretion in urine, plasma electrolyte concentration,
      hematocrit content and fluid excretion in urine increased significantly in the
      hypokinetic animals when compared with the control animals. During the initial
      seven days of the postexperimental period, water intake increased significantly
      while hematocrit level, water content in blood, and electrolyte plasma
      concentration remained markedly higher, and the fluid electrolyte excretion and
      electrolyte concentration thereof in urine decreased significantly. However, all
      these changes reverted back to the control level by the end of the post
      experimental period. It was concluded that prolonged hypokinesia (HK) and the
      initial stages of post hypokinesia are associated with significant sodium and
      potassium changes and water consumption and elimination disturbances.

PMID- 9153800
TI  - Re-inventing the wheel: assessing malignant spinal cord compression outcomes.

PMID- 9153801
TI  - Intra-abdominal fluid collections after liver transplantation.
AB  - Fluid collections are commonly seen following orthotopic liver transplantation.
      The majority of these collections are not infected and resolve spontaneously.
      However, infected collections are associated with significant morbidity and
      mortality and usually require drainage. Clinical signs of infection are
      frequently masked following transplantation due to immunosuppression.
      Intrahepatic collections usually represent abscesses or bilomas and invariably
      require intervention. Altered anatomical relationships result in signs that
      frequently help to differentiate these from loculated fluid within hepatic
      fissures. Other imaging features indicating infection include the presence of gas
      where none was seen previously, the development of a discrete wall and changes in
      the surrounding liver.

PMID- 9153803
TI  - Stereotactic large-gauge core biopsy: its role in the diagnosis of non-palpable
      mammographic abnormalities presenting to a screening service.
AB  - A retrospective study of large-gauge core biopsy (LGCB) of 206 non-palpable
      mammographic abnormalities detected at routine screening in a community-based
      clinic accredited with the Australian National Program for the Early Detection of
      Breast cancer, was performed to ascertain the role of LGCB as an alternative to
      diagnostic surgical biopsy within such a programme. Of the 51 malignancies
      diagnosed by LGCB and proceeding to treatment, no false-positives were found and
      agreement as to the presence, or otherwise, of invasion between core and open
      biopsy was 95%. Once malignancy was established by LGCB, one-stage treatment was
      possible in 74.5% of cases. A total of 114 lesions were considered to be benign
      and returned to routine screening. One interval cancer subsequently developed in
      this group. Incongruity between the pathological diagnosis from core biopsy and
      the mammographic image occurred in 29 cases, representing potential mistargeting
      in 14.1% of cases. Four cancers were discovered in this group when the patients
      subsequently proceeded to surgical biopsy, making an overall false-negative rate
      of 2.4%. No core biopsy sample was considered inadequate for pathological
      assessment and no lesion proved inaccessible to targeting. There was no long-term
      morbidity. We believe that LGCB is a safe, reliable and cheaper alternative to
      diagnostic surgical biopsy, but a close correlation of pathology and mammography
      is required to avoid the erroneous return of women to routine recall.

PMID- 9153802
TI  - Magnetic resonance imaging of musculoskeletal lesions: comparison of three fat
      saturation pulse sequences.
AB  - Fat-saturation (FS) pulse sequences can improve the detection of musculoskeletal
      lesions. We prospectively compared contrast-enhanced T1-weighted FS spin-echo
      (SE) images, T2-weighted FS fast spin-echo (FSE) images and inversion recovery
      (IR) FSE images to determine if any of these three pulse sequences is superior
      for depicting bone marrow and soft tissue lesions. T1-weighted FS-SE images (400
      680/10-20 [TR/TE]) after intravenous injection of gadolinium
      diethylenetriaminepentaacetic acid (DTPA), T2-weighted FS-FSE (2400-4200/96-112)
      and IR-FSE (3700-6000/12-14/170 [TR/TE/TI]) images were obtained with a 1.5-T
      magnet system in 35 patients. The visibility, margination and extent of 37 bone
      marrow and 67 soft tissue lesions, image uniformity, susceptibility and motion
      artefacts were qualitatively analysed by four radiologists. The number and size
      of lesions detected, the mean lesion signal-to-noise ration (S/N) and contrast-to
      noise ratio (C/N) were also statistically compared. More bone and soft-tissue
      lesions were detected on the IR-FSE and T2-weighted FS-FSE than the T1-weighted
      FS-SE images. The IR-FSE images were significantly better than the T2-weighted FS
      FSE and T1-weighted FS-SE images for bone marrow lesions conspicuity (P < 0.01).
      The soft-tissue lesions were also more conspicuous on the IR-FSE and T2-weighted
      FS-FSE images than on the T1-weighted FS-SE images (P < 0.005). The lesion extent
      and image quality were similar on all three sequences while motion artefacts were
      most severe on the IR-FSE and least severe on the T1-weighted FS-SE images (P <
      0.001). Fat saturation was maximal on the IR-FSE images, resulting in a
      significantly higher mean C/N of bone marrow lesions. The mean C/N of soft-tissue
      lesions was higher on the T2-weighted FS-FSE images although the differences were
      not significant. The T2-weighted FS-FSE and IR-FSE sequences are superior to the
      contrast-enhanced T1-weighted FS-SE sequence for depicting musculoskeletal
      lesions. Bone marrow lesion conspicuity is greater on the IR-FSE images, with
      comparable scan time and image quality but more motion artifacts.

PMID- 9153804
TI  - Schwannoma in the vestibule and cochlea.
AB  - Schwannoma of the vestibule or the cochlea is an unusual lesion. In the past,
      most examples have been found at autopsy or as unsuspected findings at surgery
      for vertigo. The symptoms of isolated labyrinthine schwannoma may be
      indistinguishable from advanced Meniere's disease. Magnetic resonance imaging has
      led to pre-operative diagnosis in some cases. Two cases of schwannoma within the
      labyrinth from a series of 339 symptomatic acoustic tumours, are presented and
      the imaging findings are discussed.

PMID- 9153805
TI  - Computed tomography changes following cryotherapy for hepatic cancer.
AB  - Encouraging survival and tumour marker results have been described in patients
      where the focally destructive technique, hepatic cryotherapy, is used to treat
      primary and secondary hepatic malignancy. Radiology allows assessment of the
      cryotherapy procedure and follow-up treatment. This paper aims to review and
      describe the appearance of hepatic cryotherapy by CT.

PMID- 9153806
TI  - Plain radiography and computed tomography of invasive thymomas: clinico
      radiologic-pathologic correlation.
AB  - Fifteen computed tomography (CT) scans in nine patients with invasive thymoma are
      presented. The CT findings were an anterior mediastinal mass (89%), pleural
      deposits (78%), local infiltration of the mediastinum (100]), invasion of the
      cardiovascular structures (22%), lung invasion (11%) and diaphragmatic or
      subdiaphragmatic deposits (33%). Radiologic-pathologic correlation available in
      six patients showed a sensitivity of 89.5%, specificity of 87.5% and accuracy of
      88.6% for CT. We conclude that CT is superior to plain radiography in the
      diagnosis of invasive thymoma. It provides an accurate pre-operative assessment
      by better demonstration of the full extent of abnormalities, and is useful in
      surgical planning, monitoring of therapeutic response and detecting recurrence.

PMID- 9153807
TI  - Helical computed tomography in the assessment of abdominal aortic pathology.
AB  - A pilot study was undertaken to evaluate the role of helical computed tomography
      in the assessment of abdominal aortic pathology. A total of 17 patients underwent
      intra-arterial digital subtraction of angiography (IADSA) and helical computed
      tomography, with eight patients undergoing subsequent operative intervention. A
      comparison of radiological findings between IADSA and helical computed tomography
      (CT) was made and, where applicable, a comparison was made with operative
      findings. Pathology included abdominal aortic aneurysm (AAA) (n = 12), thoraco
      abdominal aneurysm (n = 2) and dissection (n = 1), graft distension following AAA
      repair (n = 1) and plaque haemorrhage in the distal aorta following percutaneous
      transluminal angioplasty (PTA) of the iliac artery (n = 1). Planned operative
      management as based on pre-operative helical CT imaging findings, in particular
      with reference to the type of graft used (straight or bifurcated) was not changed
      at operation. Our findings on helical CT in regards to AAA, thoroco-abdominal
      aneurysm and dissection correlated well with angiography and surgery findings.

PMID- 9153808
TI  - Imaging of maxillary osteoradionecrosis.
AB  - Over a 3-year period, four cases of maxillary osteoradionecrosis were diagnosed
      in patients undergoing radiotherapy for nasopharyngeal carcinoma at the Queen
      Mary Hospital, Hong Kong, giving an estimated incidence of 0.8%. Patients with
      this complication presented after a mean period of 34 months post-radiotherapy.
      Risk factors that were identified were dental problems, and more than one full
      course of radical radiotherapy. Serial CT scans in the axial and coronal planes
      were useful in demonstrating the development, extent and features of maxillary
      osteoradionecrosis such as bony sclerosis, the destruction of maxillary antral
      walls and adjacent bony structures, and in excluding recurrent tumour.

PMID- 9153809
TI  - The efficacy of treatment for malignant epidural spinal cord compression.
AB  - The aims of this study were to document the efficacy of treatment and to identify
      factors that were predictive of the outcome in malignant epidural spinal; cord
      compression. The medical records of patients treated at the Prince Henry and
      Prince of Wales Hospitals in the period 1980-1989 with a diagnosis of malignant
      epidural spinal cord compression were reviewed. A total of 94 patients were
      eligible for the study and were treated by radiotherapy alone (37), surgery alone
      (19) and surgery followed by radiotherapy (38). Efficacy was determined by
      measuring complete resolution of symptoms and signs at 1 month after
      presentation, and also by using an overall functional improvement score (FIS).
      Complete resolution of individual pre-treatment symptoms that were measured 1
      month after treatment occurred as follows: pain (30/88), sensory disturbance
      (12/61), weakness (8/17), bladder dysfunction (10/42), and bowel dysfunction
      (10/36). Complete resolution of motor deficit occurred in 7/82 and of sensory
      deficit in 9/73. The ability to walk was regained in 19/51 previously non
      ambulatory patients, and bladder function improved sufficiently to remove an
      indwelling catheter in 9/32 previously catheterized patients. As judged by FIS,
      67 patients improved, 15 patients remained stable and 12 patients deteriorated.
      Of the treatments given, a combination of surgery followed by radiotherapy was
      associated with the greatest functional improvement (P = 0.001). The coexistence
      of 'liver failure' was the only patient-related factor identified which was
      associated with outcome (P = 0.041). The treatment of malignant spinal cord
      compression appears to be worthwhile; however, the outcome of treatment is not
      easy to predict from pretreatment factors. A 'functional improvement score' may
      be useful in assessing treatment efficacy.

PMID- 9153810
TI  - Comparative role of three-dimensional radiotherapy planning and inhomogeneity
      corrections in carcinoma of the tongue.
AB  - The authors have assessed the role of computerized three-dimensional (3-D) and
      traditional (TD) radiotherapy planning and inhomogeneity corrections in improving
      target volume coverage and normal tissue sparing in carcinoma of the tongue.
      Coverage of target volumes in 3-D versus TD plans revealed the following. Volume
      receiving 95% of dose, clinical target volume (CTV): 1-68% versus 0-24%; gross
      tumour volume-lymph nodes (GTV-l): 0-80% versus 0-20%; gross tumour volume
      primary tumour (GTV-II): 0-65% versus 0-26%. Dose to 95% of target volume CTV 77
      92% versus 76-87%; GTV-I: 81-90% versus 61-88%; GTV-II: 82-93% versus 68-87%.
      Minimum dose to 5% of target volume, CTV: 77-93% versus 74-81%; GTV-I: 81-90%
      versus 61-88%; GTV-II: 76-93% versus 68-87%. Minimum dose to a volume of no less
      than 5% of the target volume, CTV: 93-98% versus 88-96%; GTV-I: 87-100% versus 88
      97%; GTV-II: 86-98% versus 88-96%. A new parameter (inhomogeneity difference) was
      devised to study target volume dose homogeneity and was found to be very useful.
      Dose to two-thirds of the parotid glands in 3-D versus TD plans showed a mean of
      46 versus 65% for right parotid glands and 44 versus 56% for left parotid glands
      in all patients. Better tumour dose homogeneity, increased mean tumour dose,
      avoidance of geographic misses and better parotid sparing was achieved in 3-D
      plans as compared to TD plans. We could not demonstrate any role for
      inhomogeneity corrections using currently available computerized dose algorithms.

PMID- 9153811
TI  - Skin dose from radiotherapy X-ray beams: the influence of energy.
AB  - Skin-sparing properties of megavoltage photon beams are compromised by electron
      contamination. Higher energy beams do not necessarily produce lower surface and
      basal cell layer doses due to this electron contamination. For a 5 x 5 cm field
      size the surface doses for 6 MVp and 18 MVp X-ray beams are 10% and 7% of their
      respective maxima. However, at a field size of 40 x 40 cm the percentage surface
      dose is 42% for both 6 MVp and 18 MVp beams. The introduction of beam modifying
      devices such block trays can further reduce the skin-sparing advantages of high
      energy photon beams. Using a 10 mm perspex block tray, the surface doses for 6
      MVp and 18 MVp beams with a 5 x 5 cm field size are 10% and 8%, respectively. At
      40 x 40 cm, surface doses are 61% and 63% for 6 MVp and 18 MVp beams,
      respectively. This trend is followed at the basal cell layer depth. At a depth of
      1 mm, 18 MVp beam doses are always at least 5% smaller than 6 MVp doses for the
      same depth at all field sizes when normalized to their respective Dmax values.
      Results have shown that higher energy photon beams produce a negligible reduction
      of the delivered dose to the basal cell layer (0.1 mm). Only a small increase in
      skin sparing is seen at the dermal layer (1 mm), which can be negated by the
      increased exit dose from an opposing field.

PMID- 9153812
TI  - Intraluminal brachytherapy in the treatment of bile duct carcinomas.
AB  - Patients with carcinoma of the biliary tract have a poor prognosis because the
      disease is often unresectable at diagnosis. Intraluminal brachytherapy has been
      reported as an effective treatment for localized cholangiocarcinoma of the
      biliary tract. The purpose of our study was to analyse the survival of patients
      treated with brachytherapy and make some recommendations regarding its use.
      Fifteen patients underwent brachytherapy via a trans-hepatic approach at the
      Royal Prince Alfred Hospital from 1983 to 1993. Eleven patients had low-dose rate
      brachytherapy and four patients had high-dose rate treatment. There were nine
      males and six females. The median age was 64 years. Other treatment included
      bypass procedures in two patients, endoscopic stents in 14 patients and external
      beam irradiation in one patient. The median survival was 12.5 months and 47% of
      the patients survived 1 year. The only complication reported was cholangitis
      which was seen in one patient. There did not seem to be any difference in
      survival or complications between low- and high-dose rate brachytherapy. We
      conclude that the addition of intraluminal brachytherapy after biliary drainage
      prolongs survival and is a safe and effective treatment, but patients still have
      a high rate of local failure, and further studies will be needed to address this
      problem.

PMID- 9153813
TI  - Acetabular labrum tear in a 15-year-old male: diagnosis with correlative imaging.
AB  - A 15-year-old male with unresolved hip pain after minor trauma is presented. The
      diagnosis of an acetabular labral tear was made using correlative scintigraphic
      and magnetic resonance (MR) imaging, obviating the more invasive investigations
      of arthrography or arthroscopy of the hip. The clinical and radiological features
      of this lesion are reviewed. Undiagnosed, acetabular labral tears may result in
      considerable morbidity. Appropriate operative or conservative management of the
      condition usually provides symptomatic relief.

PMID- 9153814
TI  - Leiomyosarcoma of the oesophagus: a case report and literature review of
      leiomyosarcoma.
AB  - Leiomyosarcomas are uncommon tumours. Oesophageal leiomyosarcomas are even rarer.
      A case is presented of this rare tumour which on review of the literature seems
      to be the first patient surviving 22 years from the original treatment. We
      include a literature review of the clinical behaviour and management of
      leiomyosarcoma.

PMID- 9153815
TI  - Benign hepatic portal venous gas following blunt abdominal trauma.
AB  - A case of transient hepatic portal venous gas (HPVG) following blunt abdominal
      trauma is presented. No evidence of a serious mucosal breach or direct
      complication was seen. Benign forms of HPVG are being increasingly reported and
      must be considered in order to avoid unnecessary invasive procedures.

PMID- 9153816
TI  - Budd-Chiari syndrome: intractable ascites managed by a trans-hepatic portacaval
      shunt.
AB  - Transjugular intrahepatic portosystemic shunts (TIPS) have recently been used to
      manage the portal hypertensive complications of the Budd-Chiari syndrome. We
      report this application of TIPS (to our knowledge the first such application in
      Australia) in a young man with an excellent result and no major complications.
      This treatment offers an alternative to portacaval shunt surgery and has the
      advantage of bypassing a stenosed or compressed inferior vena cava. Additionally,
      the procedure does not complicate liver transplantation surgery if this is
      indicated at a later date.

PMID- 9153818
TI  - Giant thrombosed aneurysm associated with an arteriovenous malformation: case
      report and review of the literature.
AB  - The association of cerebral arteriovenous malformations and intracranial
      aneurysms has been well documented. Among these are a subset of giant aneurysms
      in association with arteriovenous malformations which are relatively rare. We
      present a case report and a brief review of the literature regarding this entity.

PMID- 9153817
TI  - Phlegmonous enteritis: an unusual cause of abdominal pain.
AB  - Phlegmonous enteritis is a rare infective inflammatory condition of the gut which
      is difficult to diagnose and which is often fatal. Although first described more
      than 150 years ago, very few cases have subsequently appeared in the literature.
      In this case the diagnosis of atypical small intestinal pathology was suggested
      by unusual CT findings. Coupled with the clinical picture, this prompted
      laparotomy which in turn confirmed the diagnosis of phlegmonous enteritis. A
      literature review discusses the epidemiology, predisposing conditions, postulated
      aetiologies and treatment.

PMID- 9153819
TI  - Retrobulbar hydatid cyst: assessment of two cases.
AB  - A 54-year-old man with a unilocular hydatid cyst within the infero-posterior
      angle of the orbit and a 6-year-old male child with a unilocular hydatid cyst
      within the supero-medial angle of the orbit are presented. The retrobulbar cysts
      were diagnosed with computed tomography and ultrasonography and were treated
      after serologic confirmation.

PMID- 9153820
TI  - A rare intrahepatic portacaval tubular shunt in a patient with spastic
      paraparesis.
AB  - Although there are numerous communications between the portal and systemic venous
      systems, intrahepatic portosystemic venous shunts are not frequently encountered
      in clinical practice. Here we report a patient who presented with spastic
      paraparesis, who was found to have chronic liver disease with tubular
      intrahepatic portacaval shunting.

PMID- 9153821
TI  - Diastematomyelia associated with intramedullary tumour in a hemicord: a report of
      two cases.

PMID- 9153822
TI  - Vertebral hydatid disease.
AB  - Hydatid disease affecting the bones is a rare condition, its incidence ranging
      from 0.5-2% of all cases of hydatidosis. The bones most often involved are the
      vertebrae (44%). A 22-year-old man presented to the hospital with low back pain.
      A CT scan revealed intracanal and paravertebral cystic lesions at the level of L5
      S1 with destruction of the corpus and lamina, and sacral foramen invasion. An
      operation was performed and histopathological findings confirmed the diagnosis.
      In countries where hydatidosis is endemic, the possibility of the disease must be
      borne in mind.

PMID- 9153823
TI  - Radial scar and tubular carcinoma of the breast.
AB  - A case of tubular carcinoma within a radial scar pattern is reported. The aim of
      this study is to support the opinion of the authors who believe that there is a
      relationship between tubular carcinoma and radial scar. We think that surgical
      biopsy should be recommended in all cases of stellate lesions detected at
      mammography.

PMID- 9153824
TI  - Unusual computed tomography appearance of Castleman disease.
AB  - A case is presented here of Castleman disease in an uncommon location.
      Ultrasonography demonstrated a large hypoechoic mass with multiple vascular
      channels. On computed tomography, the lesions with a nodular contour were located
      lateral to the carotid sheath on the right side, and demonstrated a variegated
      enhancement pattern.

PMID- 9153825
TI  - Problems in differentiating intradural lipoma from dermoid on magnetic resonance
      imaging.
AB  - Spinal intradural subpial lipomas are rare lesions. This case report emphasizes
      the role of MRI in diagnosing this lesion and in delineating its location.
      However, a dermoid cyst with a high lipid content of mixed triglycerides and
      unsaturated fatty acids without cholesterol may present the same appearance as an
      intradural lipoma and cannot be differentiated from it even with the use of short
      T1 inversion-recovery (STIR) images.

PMID- 9153826
TI  - Desmoplastic fibroma of the proximal ulna.
AB  - A young man presented with desmoplastic fibroma in the proximal ulna. This rare
      tumour was treated by curettage and bone grafting.

PMID- 9153827
TI  - A case of bladder agenesis.
AB  - Agenesis of the bladder is a rare anomaly, and it is usually associated with the
      absence of the urethra. In the case report herein, a normal urethra was found
      with ureters emptying into the posterior urethra. The right kidney was non
      functioning and small.

PMID- 9153828
TI  - Sonographic evaluation of biliary ascariasis.
AB  - In a prospective 6-month study, sonographic diagnosis of biliary ascariasis was
      made in 14 patients; in nine patients, the diagnosis was confirmed by endoscopic
      retrograde cholangiopancreatography and bile analysis, while in five patients,
      confirmation was obtained by proven intestinal infestation. No false-positive or
      false-negative cases were encountered. Ascariasis of the biliary tract was seen
      on ultrasound as echogenic, non-shadowing images, either as single or multiple
      strips, with visualization of the digestive tract of the worm as an anechoic
      inner tube, or as amorphous fragments. Follow-up sonograms helped in detection of
      worm expulsion following medical therapy in five patients, while endoscopic
      extraction of the worm was performed in four patients. In three patients,
      disappearance of the worm from the biliary tract was noted following a
      therapeutic sphincterotomy, and two patients detected to have a worm within the
      gall-bladder were operated on. In all patients, serial sonograms revealed
      disappearance of the worm, and the regression of biliary tract dilatation.

PMID- 9153829
TI  - Tail-gut cyst.

PMID- 9153830
TI  - A review of the use of radio-isotopes in medicine and medical research in
      Australia (1947-73).
AB  - Recent reports in the Australian media have claimed that after the Second World
      War 'hundreds of (Australians) were injected with radioactive materials in
      medical experiments that continued in Australian hospitals until the 1960s'.
      These claims prompted a review of archival records of the Australian Radiation
      Laboratory (ARL) that are held by the Australian Archives pertaining to the
      medical uses of radio-isotopes during the period 1947-73. The material examined
      indicates that the procurement, distribution, and therapeutic and diagnostic uses
      of radio-isotopes were stringently controlled by the Radio-isotopes Standing
      committee (RSC) until 1973, when the responsibility of regulation of medical uses
      of radio-isotopes passed to the Therapeutic Goods Administration. On the basis of
      available information it appears that the claims made by the media that many
      Australians were subjected to unconscionable medical experiments are unjustified.
      A full report has been released by the Commonwealth Minister for Human Services
      and Health. The following is an abridged version of that report, detailing some
      of the more contentious uses of radio-isotopes for medical purposes in Australia
      during the period 1947-73.

PMID- 9153831
TI  - Case quiz. Carotid body tumor.

PMID- 9153832
TI  - Postoperative radiotherapy for Duke's B and C rectal cancer: Peter MacCallum
      Cancer Institute experience.

PMID- 9153833
TI  - Bacteraemia caused by periodontal probing.
AB  - Bacteraemia of oral origin may result in infective endocarditis in susceptible
      individuals. The aim of this pilot study was to investigate the occurrence of
      bacteraemia due to periodontal probing. Thirty patients (15 male, 15 female; mean
      age 42.7 years) with untreated periodontitis were investigated. All were free of
      significant medical disorders and none had taken antibiotics in the previous
      month. Prior to and immediately following periodontal probing, 20 mL of venous
      blood were obtained from each patient and inoculated into aerobic and anaerobic
      blood culture bottles and incubated. Negative bottles were monitored continuously
      for three weeks before being discarded. Periodontal probing consisted of
      measuring pockets at six points around each tooth and recording the presence or
      absence of bleeding. A positive bacteraemia was recorded for three of the
      patients prior to probing. One patient exhibited Prevotella species whilst two
      exhibited skin commensals. Following probing, 13 patients (43 per cent) exhibited
      bacteraemia of oral origin. Viridans streptococci were the most common isolates
      (45 per cent). No significant correlations were found between bacteraemia and the
      severity of periodontitis or extent of bleeding on probing. The results indicate
      that periodontal probing can cause bacteraemia in patients with periodontitis. It
      would be advisable for patients considered at risk of developing infective
      endocarditis to receive antibiotic prophylaxis for periodontal probing if they
      have radiographic evidence of periodontitis.

PMID- 9153834
TI  - Effect of tooth-related factors on the shear bond strengths obtained with CO2
      laser conditioning of enamel.
AB  - Carbon dioxide (CO2) lasers are capable of producing surface irregularities in
      human enamel which resemble those resulting from etching of enamel with
      orthophosphoric acid. This report presents the results of a laboratory study
      which examined the effect of selected tooth-related variables on shear bond
      strength between a current generation bonding agent (Scotchbond MultiPurpose) and
      acid-etched or laser-conditioned human enamel. There were no significant
      differences in shear bond strength between human maxillary central incisor teeth,
      first premolars, and third molars in either the acid etch or laser-conditioned
      groups. Polishing of enamel to give a flat surface increased the shear bond
      strength obtained with acid etching, but did not alter significantly bond
      strengths achieved with laser conditioning. There was a tendency for a higher
      bond strength with acid etching, but not with laser conditioning, in porcine
      molar enamel compared with human molar and bovine incisor enamel. In terms of the
      mode of operation of the laser, the repetitively pulsed mode resulted in a two
      fold improvement in shear bond strength compared with the single pulse mode.
      These results indicate that shear bond strengths in the order of 10 MPa can be
      obtained reliably on human teeth using laser conditioning with pulsed modes in
      the absence of any other preparation of the natural enamel surface.

PMID- 9153835
TI  - Effects of preterm birth on oral growth and development.
AB  - Preterm and low birthweight children comprise approximately 6 per cent of all
      live births. They are prone to many serious medical problems during the neonatal
      period which may affect the development of oral tissues. The present paper
      reviews the results of this author's own decade of research into the oral
      development of preterm children in the light of current understanding of the
      field. Studies have shown a high prevalence of generalized enamel hypoplasia in
      the primary dentition of around 40-70 per cent in preterm children which is
      likely to be associated with low bone mineral stores. The clinical significance
      of enamel defects is poor aesthetics, and predisposition of the lesions to dental
      caries. Other dental defects observed in preterm children are localized enamel
      hypoplasia, crown dilacerations, and palatal distortions which are usually
      associated with traumatic laryngoscopy and prolonged endotracheal intubation.
      Furthermore, recent studies have demonstrated that the rate of dental
      development, and dental eruption may be affected by preterm birth. Children with
      the lowest birthweight and shortest gestational ages have the lowest rates of
      dental development, particularly before six years of age. The results of these
      clinical studies may have significant implications in the dental management of
      preterm children.

PMID- 9153836
TI  - Prior fluoridation in childhood affects dental caries and tooth wear in a south
      east Queensland population.
AB  - Fluoride exposure in early life has an effect on dental caries experience, but
      does it affect tooth wear in later life? Ninety-six South East Queensland
      subjects were studied. Their histories revealed three groups; a fluoride (F-) in
      water supply, a F- by supplement, and a non-fluoridated (non F-) group.
      Significantly higher caries experience was found in the non-F- group compared
      with F- in water group and the F- supplement group. No statistically significant
      difference in caries experience was found between the F- in water and F-
      supplement groups. Overall, tooth wear affected more sextants of the dentitions
      of non-fluoridated, high-caries subjects than of fluoridated low-caries subjects.
      Comparisons of wear patterns on sextants of the dentitions, between the
      fluoridated and non-fluoridated groups, revealed that in sextants where attrition
      was present no marked differences were discernible between the two groups.
      However, in most sextants where incisal, palatal, occlusal or non-occlusal
      erosion was found, this type of wear was commoner in non-fluoridated subjects.
      The exceptions were the mandibular molar sextants, where prior fluoride-exposure
      did not appear to protect against occlusal erosion patterns. This study showed
      that fluoride exposure during the first 12 years of life, which reduced dental
      caries in this population, may also protect teeth from wear to some extent.

PMID- 9153837
TI  - Medical emergencies in dental practice and choice of emergency drugs and
      equipment: a survey of Australian dentists.
AB  - This is a report of a postal questionnaire survey of 1250 general dental
      practitioners regarding occurrence of medical emergencies and their choice of
      emergency drugs and equipment. The response rate was 65 per cent and the results
      showed that about one in seven practitioners had had to resuscitate a patient.
      The most common medical emergencies were adverse reactions to local anaesthetics,
      grand mal seizures, angina pectoris and hypoglycaemia (insulin shock). Nearly all
      respondents (96 per cent) believed that dentists need to be competent in
      cardiopulmonary resuscitation, just over a half (55 per cent) felt they were
      competent in CPR on graduation and a similar figure (57 per cent) felt they could
      perform effective single person CPR for five minutes. Almost two-thirds (64 per
      cent) had undertaken CPR courses since graduation. Additionally, the most
      commonly kept emergency drugs were oxygen (63 per cent) and adrenaline (22 per
      cent), while the most commonly kept emergency equipment was a manual resuscitator
      (recoil bag-valve-mask type) which was kept by 27 per cent of the practitioners.

PMID- 9153838
TI  - Analysis of workplace injuries in a dental school environment.
AB  - Workplace injuries at the University of Queensland Dental School during the
      period 1992-1994 were assessed to determine their incidence, and the associated
      indirect costs, causal factors, and appropriate preventive strategies. Overall,
      dental chairside assistants experienced a higher incidence of injuries than
      students both on a per worker and per time basis. Of the injuries with a low risk
      of cross-infection, burns and scalds from sterilizing equipment, and eye injuries
      in laboratories were the most common. This emphasizes the importance of wearing
      appropriate protective equipment in areas outside the treatment zone, and the
      need for signage and education. Common causes of sharps injuries were burs left
      in handpieces, two-handed needle recapping, and cleaning of probes in the
      sterilizing room. Changes to techniques and equipment would prevent such
      incidents. A range of factors which contribute to the calculation of indirect
      costs following injuries in the dental workplace are identified.

PMID- 9153839
TI  - Audit of waste collected over one week from ten dental practices. A pilot study.
AB  - An audit of the waste practices of ten general dental surgeries identified
      problems that have occurred due to the lack of specific dental guidelines or
      codes of practice in this area. Occupational health and safety requirements for
      types and locations of sharps containers, and lack of consensus on what
      constitutes a sharp, were identified as areas needing attention. Cross-infection
      control items, such as gloves, masks, single-use cups, and protective coverings,
      were found to constitute up to 91 per cent of total waste. When infectious waste
      was reclassified by the audit team as 'that waste which was visibly blood
      stained,' a reduction in waste in this category was made, during the audit, at
      each practice. The practice of disposing of radiographic fixer and developer into
      the sewerage system occurred in three out of the ten practices, even though the
      Australian Dental Association Inc. has discouraged this practice.

PMID- 9153840
TI  - Bone resorption and serum levels of vitamin D metabolites in the
      hypophosphataemic rat.
AB  - The supplementation of a low phosphate diet with vitamin D has been shown to
      result in an increase in bone resorption in the hypophosphataemic rat. The aim of
      the present study was to determine if administration of vitamin D to rats fed a
      vitamin D- and phosphate-depleted diet would result in an increase in the
      circulatory levels of the active vitamin D metabolite 1,25(OH)2D3 and an
      associated increase in bone resorption. Three groups of weanling Sprague-Dawley
      rats were used. The first group consisted of control animals on a normal
      laboratory stock diet and the second and third groups were experimental animals
      receiving a vitamin D- and phosphate-deficient diet with the third group
      receiving vitamin D supplementation. All animals were housed in the dark. After
      30 days on the diet the experimental animals received 0.1 mmol NaH2PO4 by
      intraperitoneal injection. Blood was sampled at zero, 3, 6, 18 and 48 h post
      injection and analysed for the vitamin D metabolites 25(OH)D3 and 1,25(OH)2D3,
      calcium and inorganic phosphate (Pi). The serum analyses revealed that the level
      of 25(OH)D3 in the hypophosphataemic animals was significantly lower than that of
      the control animals. However, the 1,25(OH)3D3 level was initially significantly
      higher, then dropped to the control level at 18 h post-intraperitoneal injection
      of phosphate. Further, the serum levels of 25(OH)D3 and 1,25(OH)2D3, calcium and
      Pi in the hypophosphataemic animals supplemented with vitamin D were
      significantly higher than those of the vitamin D-deficient animals. Also the
      vitamin D-supplemented animals exhibited significantly greater levels of bone
      resorption. These results therefore, are consistent with a role of 1,25(OH)2D3 in
      bone resorption in hypophosphataemic rats.

PMID- 9153841
TI  - Comparison of different methods of temporomandibular joint disc reconstruction-
      an animal model.
AB  - The optimum method of temporomandibular joint (TMJ) reconstruction has not been
      defined despite numerous surgical treatments and several well controlled clinical
      trials. Animal models offer an experimental method allowing direct comparison of
      standardized surgical techniques. Advanced osteoarthrosis was induced bilaterally
      in 12 mature merino sheep. Three months alter unilateral surgical reconstruction
      was performed. Four sheep had discectomy alone, four discectomy with fresh TMJ
      disc grafts, and four discectomy with fresh auricular grafts. All three surgical
      methods resulted in some reversal and repair of the osteoarthritic process, with
      the best result being from the auricular graft, next discectomy alone, next the
      disc graft, with the untreated osteoarthritic joint showing the most advanced
      pathosis. This study supports the role of surgical reconstruction in advanced
      degenerative disease of the temporomandibular joint, in particular, auricular
      graft reconstruction.

PMID- 9153842
TI  - Cell surface structures of Actinomyces israelii.
AB  - Actinomyces israelii is the most common cause of human actinomycosis, a chronic
      granulomatous infection. Periapical actinomycosis involving A. israelii has been
      identified as an important cause of failure of conventional endodontic treatment.
      Structures on the bacterial cell surface have been implicated in the
      pathogenicity of Actinomyces. In this study the ultrastructure of A. israelii was
      investigated by electron microscopy. Negatively stained preparations revealed the
      presence of hairlike fimbriae protruding through a thick surface coat on some
      species, whilst thin sectioning disclosed a Gram-positive cell wall surrounded by
      a fuzzy outer coat. These structures may be important for the pathogenicity of A.
      israelii.

PMID- 9153843
TI  - Palatal rugae patterns in Australian aborigines and Caucasians.
AB  - The purpose of this study was to determine whether rugae patterns change with age
      and to compare the number and pattern of rugae in Australian Aborigines with
      those of Caucasians. For the longitudinal part of the study, serial dental casts
      of ten Aborigines, from 6 to 20 years of age, were examined and rugae patterns
      were recorded. To enable comparisons to be made between different ethnic groups
      an additional 100 dental casts of Australian Aborigines and 200 casts of
      caucasians, ranging in age from 13 to 17 years, were examined. Characteristics
      observed were number, length, shape, direction and unification of rugae. The
      length of rugae increased significantly with age but the total number of rugae
      remained constant. Thirty-two per cent of rugae showed changes in shape, while 28
      per cent displayed a change in orientation. In contrast to studies suggesting
      that rugae move forward with age, the majority of Aboriginal rugae that changed
      direction moved posteriorly. Changes in rugae patterns have been assumed to
      result from palatal growth but alterations in pattern were observed in the
      Aboriginal sample even after palatal growth had ceased. The mean number of
      primary rugae in Aborigines was higher than in Caucasians, although more primary
      rugae in Caucasians exceeded 10 mm in length than in Aborigines. The most common
      shapes in both ethnic groups were wavy and curved forms, whereas straight and
      circular types were least common. There was a statistically significant
      association between rugae forms and ethnicity, straight forms being more common
      in Caucasians whereas wavy forms were more common Aborigines.

PMID- 9153844
TI  - Neil Goldsworthy.

PMID- 9153845
TI  - Silver fluoride use.

PMID- 9153846
TI  - Methadone and caries.

PMID- 9153847
TI  - Infective endocarditis and practical guides for successful dentistry.

PMID- 9153848
TI  - Hypertension medication and periodontosis.

PMID- 9153849
TI  - Arthroscopic surgery.

PMID- 9153852
TI  - [Leg-lengthening for length inequality].
AB  - 32 patients (age range 1.5-22 years) were treated for leg-length discrepancy. 39
      lengthening procedures were performed of which 36 involved gradual distraction,
      in 2 cases chondrodiasthesis was used, and 1 had 1-step elongation. Gradual
      distraction was done according to Ilizarov, including corticotomy and a 1-week
      delay before the initiation of distraction. In 33 cases Wagner's external fixator
      was used, in 2 Ilizarov frame and in 1 an orthofix fixator. There was complete
      clinical and radiologic union in all but 1 case. Significant correction of leg
      length discrepancy and equalization of leg-length was achieved in most patients.
      In some growing patients over-correction was successfully achieved. The most
      prevalent complications were pin-site problems, axis deviation, joint subluxation
      and joint contractures. At latest follow-up most of these complications had
      disappeared. 91% of the patients either functioned normal or were only mildly
      limited.

PMID- 9153850
TI  - [Cutaneous leishmaniasis: incidental outbreak in a new endemic area?].
AB  - In the autumn of '94 we saw 32 patients with cutaneous leishmaniasis from a newly
      populated areas south of Yerucham. Yerucham had never previously been reported as
      a focus of leishmaniasis. Ongoing construction in the town and the health hazards
      that resulted may play a part in this new situation. There are a number of ways
      of controlling and preventing outbreaks leishmaniasis. They include elimination
      of the vector, Phlebotomus and its host, the gerbils as well as their food
      supply, "maloach" bushes, other health hazards and vaccination of the population.
      Patients were treated according to the severity of disease. It is still too early
      to determine whether our efforts to limit the spread of the outbreak have been
      successful.

PMID- 9153851
TI  - [Angioplasty and stenting of the carotid artery].
AB  - Percutaneous endovascular techniques are well established procedures in the
      management of peripheral vascular disease and visceral arterial stenosis. They
      are now being adapted for use in the carotid artery as well. 8 patients with 9
      extracranial carotid artery stenoses were successfully treated by percutaneous
      angioplasty, following which in 4 of them 5 stents were inserted. The stenotic
      lesions were situated in the proximal internal carotid artery and in its
      bifurcation and also in the common carotid artery. The indications for
      angioplasty in these patients were the same as for surgery. There were no major
      complications. 1 patient had transient hemiparesis lasting a few hours, and
      another had bradycardia following balloon dilation in the region of the carotid
      body. Percutaneous endovascular treatment of carotid artery stenosis is becoming
      a safe, feasible alternative to surgery.

PMID- 9153853
TI  - [Acute fungal endocarditis due to Trichosporon beigelli].
AB  - We report a 59-year-old woman with acute fungal endocarditis of a prosthetic
      valve caused by the endogenic organism, Trichosporon beigelli. This slowly
      developing disease mainly effects drug addicts who use intravenous narcotics. In
      nonaddicts it is rare, with mortality as high as 50%. There are only sporadic
      reports of T. beigelli as a complication long after open heart surgery. The
      ongoing infection is undetected for even years after the primary infection, due
      to its prolonged latent phase. We present the difficulties of diagnosis, and of
      treating the disease with a combination of surgery and of long-term chemotherapy.

PMID- 9153854
TI  - [Pediatric flexible bronchoscopy].
AB  - Between 1993-1996, 200 pediatric flexible bronchoscopies were performed.
      Indications were: chronic cough (158 children), persistent pulmonary infiltrates
      (89), recurrent stridor (28), suspected tracheobronchial foreign body (20),
      suspected tuberculosis (17) and hemoptysis (3). Some children had more than 1
      indication. 124 patients were boys (mean 4.18 +/- 2.86 years; range 1 month-15
      years) and 76 were girls (mean 4.39 +/- 2.7 years; range 4 months-15 years). The
      procedure included direct vision recorded by video-camera and bronchoalveolar
      lavage; the lavage fluid was sent for culture, Gram and Ziehl-Nielsen strains and
      for cytology. There were a few minor side effects: mild stridor which resolved
      within a few hours (10 children) and transient fever (3). This simple, flexible
      instrument was effective and helpful in the diagnosis and treatment of children
      with respiratory symptoms in a secondary hospital facility.

PMID- 9153855
TI  - [Disappointing response of chronic C hepatitis to interferon].
AB  - From February 1990 to August 1995 we treated 58 patients with chronic hepatitis C
      alfa-interferon, 3 million units 3 times weekly for 6 months. Of the 48 patients
      with adequate follow-up, 34 did not respond to treatment at all. 10 patients
      responded, but within a few months hepatic enzymes again increased. These 2
      groups can be considered failures of interferon treatment. In 4 patients enzymes
      remained normal for the duration of follow-up, (10-34 months). Even in this small
      group, 1 patient had a positive test for HCV RNA after completion of treatment. A
      partial explanation of our disappointing results may be the high prevalence of a
      subtype of C hepatitis-subtype 1b, which has recently been reported in Israel.
      This strain is particularly resistant to interferon. The means to define subtypes
      were not, and as far as we know are not yet available in Israel. Various groups
      have attempted to improve the outcome of treatment of hepatitis C, which in other
      hands too was still far from satisfactory. Thus, regimens of interferon utilizing
      higher doses and longer periods of treatment are being evaluated, as well as the
      addition of Ribavirin, which hopefully will improve results.

PMID- 9153856
TI  - [Quinidine-induced rheumatic toxicity].
AB  - 2 women with quinidine-induced lupus are presented. This condition is rare; only
      about 30 cases have been reported in the English literature. Both our patients
      had arthritis of the wrist, antinuclear antibodies with homogenous pattern and
      elevated ESR. Anti-double stranded DNA antibodies were present in 1 patient, and
      a petechial rash in the other. Complete resolution of arthritis occurred within a
      few days after quinidine withdrawal, but antinuclear antibodies persisted for
      several months.

PMID- 9153857
TI  - [Is smallpox really eradicated?].

PMID- 9153858
TI  - [Bone bank--operational and professional aspects in the orthopedic community in
      Israel].

PMID- 9153860
TI  - [Acquired melanocytic nevi in children--a beauty spot or warning sign?].

PMID- 9153859
TI  - [Selective inhibitors of cyclooxygenase-2 in upgrade in nonsteroidal anti
      inflammatory drugs].

PMID- 9153861
TI  - [Temporal arteritis--old and new].

PMID- 9153862
TI  - [Fractures of the calcaneus--new trends in management].

PMID- 9153863
TI  - [Acute gastroenteritis caused by small round viruses].

PMID- 9153864
TI  - [Imaging techniques for the shoulder].

PMID- 9153865
TI  - [Patterns of injuries and preventive measures for motorcycle accidents].
AB  - Retrospective analysis of a series of 32 motorcyclists admitted after road
      accidents was performed. 62% were injured on scooters with 50 cc engine capacity
      and most of the combined injuries occurred in this group. Most crashes occurred
      at road junctions. Riders of scooters with larger engine capacities tended to
      wear protective garments as opposed to riders with smaller engines. There was no
      correlation between engine capacity and severity of injury. We conclude that
      motorcyclists should receive special education, especially as to behavior on
      entering road junctions. We recommend that taxes on protective garments should be
      lowered in order to encourage motorcyclists to use them.

PMID- 9153866
TI  - [Confidential health care for adolescents: legal and ethical aspects].

PMID- 9153868
TI  - [Superficial femoral vein--a misleading name for a deep vein].

PMID- 9153867
TI  - [Banting and Best--75 years of insulin treatment].

PMID- 9153869
TI  - [Cellular phone interference with medical instruments].
AB  - Cellular telephones and other telecommunication equipment occasionally cause
      malfunctioning of medical equipment, including life-support equipment. We review
      such malfunctioning and relate it to Israeli and Worldwide standards, analyzing
      the characteristics of the interference in terms of amplitude and frequency. The
      results of a controlled study of interference by cellular telephones and portable
      2-way radios with medical devices in our clinical departments are also presented.
      The levels of background environmental electromagnetic noise at several sites in
      both Hadassah hospitals (Ein Karem and Mount Scopus) were measured, as well as
      signal levels of cellular telephones and other communication equipment at various
      distances and in various areas. We recommend 2 different levels of restrictions
      on the use of this equipment within the hospital. These include prohibition of
      the use of wireless telecommunication equipment in intensive care areas and
      operating theaters. In all other areas it is recommended to turn off the cellular
      telephone within 1 meter of medical devices and not to transmit (but only to
      receive) calls with a portable 2-way radio within a 5 meter distance of medical
      devices.

PMID- 9153870
TI  - [CT-guided core needle biopsy of abdominal, pelvic and retroperitoneal masses].
AB  - CT-guided core needle biopsy of abdominal, pelvic and retroperitoneal masses is
      accurate and safe and can be performed on an outpatient basis. Between 1987 and
      1995, 809 patients (age range 1-87 years) underwent 851 biopsies (minimal lesion
      diameter 1 cm). Cutting needles were always used, facilitating both cytological
      and histological diagnosis while minimizing risk of complications. A positive
      result (malignant, inflammatory or infectious) was obtained in 69% of the 809 and
      a negative result (normal tissue) in 17.4%, while in 13.6%, material for
      diagnosis was insufficient. Biopsy was repeated in 42 of them in whom
      radiological or clinical suspicion of malignancy was high. In 24 (60%) a positive
      result was obtained after the second biopsy. Significant complications occurred
      in 7 (0.8%). 1 hemo-rrhaged following liver biopsy and required blood
      transfusion. Pancreatitis occurred in 6 (2.6%) following pancreatic biopsy. An
      intraabdominal fluid collection in 1 necessitated percutaneous drainage. There
      was no mortality following the procedure and no documented case of needle-tract
      seeding of tumor. All outpatients were discharged within 3 hours of completion of
      the biopsy, without ill effects.

PMID- 9153871
TI  - [Maggot therapy for gangrene and osteomyelitis].
AB  - 5 patients with diabetic-foot were treated by maggot therapy. The most serious
      case was in a 75-year-old man who had gangrene and osteomyelitis of the right
      foot. Proteus mirabilis, Enterococcus sp., Providencia stuartii and
      Staphylococcus spec. (coagulase positive) were isolated from lesions which did
      not respond to antibiotic therapy. The patient had twice refused amputation but
      agreed to maggot therapy. Larvae of the sheep blowfly Phoenicia (Lucilia)
      sericata were used for twice-weekly treatment over a period of 7 months. Sterile
      larvae were applied to the wound and replaced every 3-4 days. After 4 months of
      treatment, the necrotic tissue around the toes and on the sole of the foot
      detached from the healthy tissue. During the last 3 months of treatment the
      larvae removed the remaining infected tissue. As therapy progressed, new layers
      of healthy tissue covered the wound. The offensive odor associated with the
      necrotic tissue and the intense pain in the foot decreased significantly. At the
      end of therapy, during which there were no complaints of discomfort, he was able
      to walk. In the 4 other patients who had relatively superficial gangrene, the
      maggots debrided the wounds within 2-4 weeks. Thereafter treatment was continued
      with antibiotics. Maggot therapy can be recommended in cases of intractable
      gangrene and osteomyelitis, when treatment with antibiotics and surgical
      debridement have failed.

PMID- 9153872
TI  - [Recurrent late hemarthrosis after total knee replacement].
AB  - A patient who had a successful total knee replacement for severe degenerative
      osteoarthritis of the right knee had an excellent functional result. 2 years
      after the operation there was spontaneous intra-articular bleeding that was
      treated successfully conservatively. Recurrent hemarthrosis 2 months later was
      treated similarly and also resolved without residual functional impairment after
      a follow-up of over 1 year. Recurrent late hemarthrosis in the knee is a fairly
      rare complication following total knee arthroplasty, but is amenable to
      conservative measures. Frequently, persistent recurrent hemarthrosis requires
      debridement of the bleeding synovium of the knee.

PMID- 9153873
TI  - [Femoral fracture following total hip replacement].
AB  - Between January 1990 and May 1996 we performed 500 total hip replacements, 6 of
      which were complicated by ipsilateral femoral fracture. Treatment was either by
      skeletal traction or by internal fixation, with or without revision-total hip
      replacement. Results of surgical treatment were superior to those of conservative
      treatment. This study supports use of Mennen plate-fixation. Further studies are
      necessary for final evaluation of the efficacy of this method.

PMID- 9153875
TI  - [Esophageal carcinoma presenting as fever of unknown origin].
AB  - Fever of unknown origin presents both a clinical and diagnostic challenge and is
      usually caused by inflammatory and neoplastic diseases. We present a unique case
      of a previously healthy 77-year-old woman whose sole complaint was fever.
      Complete hospital investigation failed to reveal the underlying process. 4 months
      after the onset of fever, dysphagia appeared and she was then diagnosed as
      suffering from squamous cell carcinoma of the esophagus. The question of early
      barium swallow X-ray in such cases is raised.

PMID- 9153874
TI  - [Gonadotropin-releasing hormone (GnRH) in selecting patients for
      varicocelectomy].
AB  - The gonadotropin-releasing hormone (GnRH) test was performed on 182 patients with
      various degrees of varicocele before and after low, inguinal, spermatic vein
      ligation, and on 18 controls. The levels of follicle-stimulating hormone (FSH)
      and luteinizing hormone, a synthetic GnRH (LH), were evaluated before and 45
      minutes after intravenous injection of 100 mcg relisorm L. FSH levels increased
      more than 2-fold in 118 patients [64.8%] and LH levels increased more than 5-fold
      in 135 patients [74.1%]). In the control group the increase was less in all
      cases. Therefore, whenever FSH increased more than 2-fold and LH more than 5
      fold, we considered the test positive (pathologic); On this basis the GnRH test
      was positive in 126 (69.2%) and negative (normal) in 56 (30.7%). Of the 126 with
      positive tests, only 32 (27.3%) still had a positive result 5-6 months after
      operation. There was correlation between a positive GnRH test and significant
      improvement in sperm parameters after varicocelectomy: of the 126 with positive
      tests before operation, sperm parameters improved in 87 patients (69%), while in
      the 56 patients with negative tests before operation, in only 7 (12.5%) was there
      improvement after correction. We conclude that a positive GnRH test indicates
      impairment of the hypothalamic-pituitary-gonadal axis caused by varicocele and
      could serve as a marker for surgical intervention with good prediction of
      outcome.

PMID- 9153876
TI  - [Coffee, caffeine and human pathophysiology].

PMID- 9153877
TI  - [New hepatotoxic viruses].

PMID- 9153878
TI  - [Viral hepatitis in the elderly].

PMID- 9153879
TI  - [Human herpesvirus-6: a new member of the herpesvirus family, a threat to AIDS,
      organ-transplanted and other immune deficient patients].

PMID- 9153880
TI  - [Advances in immunopathology and treatment of Behcet's disease].

PMID- 9153881
TI  - [Analgesic and antipyretic drugs in pregnancy].

PMID- 9153882
TI  - [Epidemiology of Helicobacter pylori].

PMID- 9153883
TI  - [Pulmonary involvement in systemic lupus erythematosus].

PMID- 9153884
TI  - [Sub-capital femoral fracture in the demented patient--is operative treatment
      effective?].

PMID- 9153885
TI  - [Whipple operation in trauma].
AB  - Pancreato-duodenectomy is a formidable operation for the critically injured
      patient. We describe a patient who sustained a stab wound to the stomach and
      duodenum. At operation this injury could not be reconstructed. A Whipple
      operation was performed in which the pancreatic stump was stapled and recovery
      was uneventful, although there was a low output fistula from the pancreatic
      stump. Limited indications for the Whipple procedure in trauma patients are
      suggested.

PMID- 9153886
TI  - [Thermal dilution injectors].

PMID- 9153888
TI  - [Plagiarism].

PMID- 9153887
TI  - [Fecaloma-induced bilateral hydroureter].

PMID- 9153889
TI  - [Separation of conjoined twins: the anesthesiologist's perspective].
AB  - Managing anesthesia care for separation of conjoined twins poses a special
      challenge for the anesthesia team. Early preparation, thorough understanding of
      the anatomical and the physiological consequences of this complex anomaly, as
      well as careful coordination with the teams of surgeons, nurses and operating
      room personnel are mandatory to assure successful separation of the conjoined
      twins. It is recommended that the mother be transferred to and the babies be
      delivered at a tertiary care medical center, like the Children's Hospital.
      Special attention is devoted during the surgical procedure to cardiovascular
      stability, drug disposition, fluid balance and temperature control. The
      multidisciplinary team approach makes this complex surgery a success. When
      postoperative survival cannot be guaranteed for both twins, close contact and
      consultation is mandated with the parents, medical personnel and religious and
      legal advisors.

PMID- 9153891
TI  - [Radiation-induced meningioma: the changing pattern of the disease].
AB  - In this country radiation-induced meningiomas were usually associated with low
      dose irradiation of the scalp of immigrants from North Africa, given as part of
      the treatment of tinea capitis. An Ashkenazi patient developed meningiomas 15
      years after high-dose irradiation for a benign lesion in the parasellar region.
      The accumulating literature about high-dose radiation-induced meningiomas is
      reviewed and attention is drawn to the ever increasing number of meningiomas
      observed in immigrants from the former Soviet Union.

PMID- 9153890
TI  - [Facial trauma: characteristics and therapy].
AB  - This department was established 35 years ago. Since then, many patients with
      facial trauma, both soldiers and civilians, have been treated and extensive
      experience has been accumulated. From 1990 to 1995, 487 patients with facial
      trauma (18.6% of the patients in the department) where hospitalized and treated.
      88.5% suffered from injuries which included facial bones, and the others from
      soft tissue injuries only. We summarize our experience, analyzing both the
      demographic and clinical characteristics of the injuries and the treatment
      administered. Based on our experience and the current literature, we present an
      overview of the issue.

PMID- 9153892
TI  - [Effectiveness of selective hepatic artery embolization in a child after blunt
      hepatic trauma].
AB  - A 9-year-old boy was admitted after a bicycle fall. Abdominal CT-scan revealed
      severe liver injury (stage IV according to the liver injury scale of the American
      Association for Surgery Trauma), including ruptured intraparenchymal hematoma
      with active bleeding. The patient was hemodynamically stable and was treated
      conservatively for the first 2 days. On the 3rd day selective hepatic artery
      angiography was performed because of abdominal distension and the need for 7
      pints of packed red blood cells. Active right hepatic artery bleeding was
      identified and treated successfully by embolization. We think that early
      angiography and selective embolization should always be considered for acute or
      continuous bleeding after liver injury.

PMID- 9153893
TI  - ["CHARGE" association].
AB  - CHARGE association represents a group of congenital anomalies with no clear
      etiology. The broad array of abnormalities, which involves several systems, has
      been the basis for the acronym CHARGE: coloboma, heart anomaly, choanal atresia,
      retarded growth and development, hypoplastic genitalia and ear malformation. We
      present 3 children with CHARGE association to illustrate the phenotypic
      variability and note the multidisciplinary treatment they received. It is
      recommended that this entity be approached in an interdisciplinary, integrated
      way to allow for faster diagnosis and better prognosis.

PMID- 9153895
TI  - [Confidentiality--privacy and public interest].

PMID- 9153894
TI  - [Efficacy and safety of acarbose treatment of NIDDM].
AB  - An uncontrolled multicenter study of the efficacy and safety of treatment of
      diabetes with acarbose was conducted on 169 NIDDM patients in 12 medical centers
      in Israel. Acarbose was administered for 19 weeks, and the patients were followed
      for an additional 12 weeks. A substantial decrease in HbA1c levels from 8.5% to
      7.5% (p < 0.001) and in postprandial serum glucose levels from 283.6 mg/dl to
      248.5 mg/dl (p < 0.01) was seen during treatment. On follow-up, HbA1c levels
      increased by 0.45% and postprandial serum glucose rebounded from 256.4 mg/dl to
      287.9 mg/dl. Acarbose was shown to be effective in treating NIDDM and to be safe
      and well-tolerated.

PMID- 9153896
TI  - [Why did the entity of effort syndrome disappear].

PMID- 9153897
TI  - [Knockout and knockin mice].

PMID- 9153898
TI  - [Interferon treatment for age-related macular degeneration].

PMID- 9153899
TI  - [Urinary retension in women].

PMID- 9153900
TI  - [Ciprofloxacin treatment for pregnant or lactating women and children?].

PMID- 9153901
TI  - [Immunological aspects of endocarditis].

PMID- 9153902
TI  - [Lamotrigine--a new antiepileptic drug for the treatment of epilepsy in
      childhood].

PMID- 9153903
TI  - [Does the effort syndrome have a right to be?].

PMID- 9153904
TI  - [Management of multicasualty event in the hospital].

PMID- 9153905
TI  - [Urban mass casualty terrorist incident: systematic management approach].

PMID- 9153906
TI  - [Arthroscopes].

PMID- 9153907
TI  - [Bronchogenic cyst].

PMID- 9153908
TI  - [Biological test for menopausal osteoporosis].
AB  - Osteoporosis has become a major public health problem in many western countries
      in which about 25% of women by the age of 65 will have had osteopenic fractures.
      The most important contributing factor to this condition is loss of gonadal
      function. This progressive disease, characterized by reduction in bone mass, may
      be prevented by estrogen replacement therapy. While there are several methods of
      diagnosing the disease when already established, there is no method that can
      identify women at high risk of developing osteoporosis. We have developed a
      biological test in which the serum of postmenopausal women is added to rat
      osteoprogenitor cell culture and its influence on proliferation, differentiation
      and mineralization of bone cells is determined. The serum of 20 menopausal women
      was examined by the biological test and the results compared to the findings of
      dual photon absorptiometry. This showed that rapid bone-losers had a
      significantly lower mineralization index as compared to nonosteopenic women (p <
      0.0001). The proliferation index (cell count) and alkaline phosphatase activity
      did not show significant differences between osteopenic and nonosteopenic groups.
      This preliminary study showed that a test based on serum reacting with a culture
      of bone cells to induce mineralization may be of value in the diagnosis of
      osteoporosis.

PMID- 9153909
TI  - [Urinary bladder transitional cell carcinoma with trophoblastic differentiation].
AB  - Transitional cell carcinoma (TCC) with trophoblastic differentiation (TD) is a
      newly recognized variant of urothelial cancer which produces placental proteins,
      predominantly beta-human chorionic gonadotropin (HCG). It has a poor prognosis.
      About 210 cases were described, mostly from North America, Europe and Japan. This
      is the first report of TCC TD in a resident of Israel's upper Galilee. A 69-year
      old man whose urinary papillary bladder tumor was established cystoscopically,
      refused treatment and stopped follow-up. 3.5 years after his last visit, he
      returned and cytologic examination revealed malignant urothelial cells, while
      intravenous pyelography disclosed a urinary bladder defect. Cystoscopy showed
      numerous papillary masses dispersed over the bladder mucosa, which were resected
      transurethrally. Histopathologic examination revealed TCC grade III, stage A.
      Tumor cells were immunopositive for beta-HCG and human placental lactogen. 4
      transurethral resections of large masses were performed within 2 months.
      Pulmonary metastases developed and the patient died 4 years after the detection
      of the urinary bladder tumor.

PMID- 9153910
TI  - [Insertion of Hickman catheters in an interventional radiology suite].
AB  - In the past 20 years Hickman catheters have gained increasing acceptance for many
      uses, including bone marrow transplantation, long-term chemotherapy, total
      parenteral nutrition, dialysis, and administration of antibiotics and fluids.
      Until the past decade these catheters were inserted in the operating room. We
      present our experience in the percutaneous placement of 203 Hickman catheters in
      an interventional radiology suite in 190 consecutive patients within a period of
      30 months. Catheter placement was successful in 202 (99.5%). The main
      complications were infections, necessitating removal of the catheter in 11 cases
      (5.4%) and unintentional dislodgement of the catheter in 8 (3.9%)-all in women
      and most on the right side. Pneumothorax and thrombosis in the catheter each
      occurred once. In another patient the guide wire broke during insertion and had
      to be percutaneously removed from the pulmonary artery. Late fracture of the
      catheter occurred in 2 others in whom the intravascular fragment was removed
      percutaneously. We believe that percutaneous Hickman catheter placement in the
      radiology suite offers advantages over traditional surgical placement.

PMID- 9153911
TI  - [Between "transparent room" and "sealed room:" professional confidentiality and
      therapeutic judgement].
AB  - Patients and therapists are concerned with the complexities of protecting medical
      confidentiality. The traditional perception of protection of patient
      confidentiality is that the individual's interest in protecting his
      confidentiality may conflict with the public's need for information, especially
      in cases involving possible danger. In fulfilling his dual role of representing
      both the patient and the public, the therapist acts according to existing laws
      and regulations. We describe 3 cases in which refraining from providing the Army
      with information in accordance with the law was recognized in retrospect as
      having caused the patient suffering, and even danger. It is recommended that the
      therapist's judgement be considered in addition to other legal criteria for
      determining whether or not to protect patient confidentiality.

PMID- 9153912
TI  - [Ischemic hepatitis in congestive heart failure after an episode of hypotension].
AB  - Ischemic hepatitis can occur as an acute episode in advanced congestive heart
      failure (CHF). The mechanism is massive necrosis of the central lobules resulting
      from acute hypoxia when low cardiac output further reduces oxygen supply,
      aggravating underlying congestion due to poor venous outflow. We describe a 70
      year-old woman with congestive heart failure for 7 years who was admitted with
      jaundice, vomiting, abdominal pain and oliguria after an episode of hypotension.
      The diagnosis of ischemic hepatitis was established by a documented episode of
      severe hypotension, followed by elevation of serum transaminases, a rise in serum
      bilirubin and LDH levels, prolonged prothrombin time and acute renal failure.
      Other causes of acute hepatitis, such as a virus or drugs were excluded, and
      improved liver and renal function followed hemodynamic stabilization. We conclude
      that ischemic hepatitis should be considered whenever acute hepatitis follows a
      recent episode of systemic hypotension, especially in the context of concomitant
      CHF.

PMID- 9153913
TI  - [Treatment of open fractures due to dog bite].
AB  - 2 patients aged 12 and 19, respectively, sustained open fractures of the wrists
      due to dog bites. Both were bitten on a wrist by Rotweiller dogs, but with
      different magnitudes of injury to bone and soft tissue. Treatment, clinical
      course and recovery are described, together with recommendations for dealing with
      open fractures due to animal bites. In the presence of considerable injury to
      soft tissue and bone, and of exposure to canine oral flora, open fractures due to
      dog bites should be dealt with as high grade open fractures.

PMID- 9153914
TI  - [Osteoid osteoma of the patella].
AB  - Osteoid osteoma is a primary, benign, bone tumor with a typical X-ray appearance.
      The diagnosis is usually straightforward when it involves the long bones of the
      leg. However it may occur in unusual locations, such as in flat and cancellous
      bones. The following case demonstrates the difficulty in diagnosing it in an
      extremely rare site. A 25-year-old woman with long-standing anterior, right knee
      pain had had 3 interventions: 2 diagnostic arthroscopies and a distal, femoral
      biopsy. Since there had been no improvement in her condition, the diagnosis of
      osteoid osteoma of the patella was suggested, supported by recent X-ray and
      scintigraphic findings. This rare condition was confirmed by biopsy of the upper
      pole of the patella, a procedure that was followed by complete recovery. 6 years
      later, she is now completely free of pain and has no clinical or X-ray evidence
      of recurrence. Review of the literature revealed only 5 previously reported cases
      of osteoid osteoma of the patella. All were diagnosed relatively late and in 1
      the tumor was diagnosed only after total patellectomy. Diagnosis of these rare
      cases that mimic much more common causes of patello-femoral pain demands a high
      index of suspicion.

PMID- 9153916
TI  - [To close or not to close atrial septal defects in adults].

PMID- 9153915
TI  - [Water intoxication following desmopressin overdose].
AB  - Water intoxication is a serious condition which may be caused by desmopressin
      overdose, with reversible or irreversible neurological complications. In the
      past, desmopressin was used in endocrinological centers for the treatment of
      antidiuretic hormone deficiency (central diabetes insipidus). Indications for
      hormone treatment have since widened, especially as an effective solution for
      nocturnal enuresis. It is now often prescribed in community clinics, and its use
      has been encouraged by extensive promotion. We describe a 15-year-old boy with
      primary nocturnal enuresis who started treatment with desmopressin 1 year prior
      to admission. He was allowed to use the drug without supervision, and drank
      excessively. The result was water intoxication which required admission for
      intensive care because of loss of consciousness and convulsions for 36 hours.

PMID- 9153917
TI  - [Does the public suffer from secondary smoke].

PMID- 9153918
TI  - [Nucleosome as an autoantigen in systemic lupus erythematosus].

PMID- 9153919
TI  - [Involvement of the immune system in bone destruction and formation].

PMID- 9153921
TI  - [Non-Q wave myocardial infarction: treatment and risk stratification].

PMID- 9153920
TI  - [Genetic defects in neurodegenerative diseases].

PMID- 9153922
TI  - [Atrial septal defect in the adult: clinical course with medical treatment, pre
      operative risk, and long-term postoperative survival].

PMID- 9153923
TI  - [Carbon monoxide: an essential modulator of blood vessel tone].

PMID- 9153924
TI  - [Recommendations for coronary catheterization, revascularization, and arrangement
      of coronary stent].

PMID- 9153925
TI  - [Smoking habits of young Israeli soldiers].
AB  - A random sample of 32,166 soldiers were interviewed (on their day of discharge
      from the Israeli Defence Forces, between 1980-1995) with regard to smoking
      habits. Among men, prevalence of current smoking was 46.8%, and among women
      32.9%. Over the study period, prevalence in men decreased 27%. Among women,
      prevalence decreased from 1981 to 1991, but since then it has steadily increased.
      Among men, mean number of cigarettes smoked decreased from 21.6 in 1989 to 16.6
      in 1995. Among women cigarettes smoked decreased from a mean of 14.3 in 1989 to
      13.1 in 1995. 65.9% of the men and 49.3% of the women had started smoking by the
      age of 18. Among men the age distribution of smoking changed hardly at all over
      the years of the study. However, the proportion of women who began to smoke in
      the youngest age bracket (15 years of younger) doubled over the course of the
      study.

PMID- 9153926
TI  - [Nicotine replacement therapy for cessation of smoking].

PMID- 9153927
TI  - [Cigarette smoking and osteoporosis].

PMID- 9153928
TI  - [Smoking and the heart].

PMID- 9153929
TI  - [Memories of a retired physician].

PMID- 9153930
TI  - [Solid organ retransplantation].
AB  - The need for solid organ retransplantation is a major factor in the shortage of
      available organs. Between 1972 and 1992, 56 out of 309 kidney transplants and 2
      out of 20 liver transplants performed in our hospital were retransplantations.
      The present study evaluates local and world experience with organ
      retransplantations in terms of the medical and ethical issues.

PMID- 9153931
TI  - [Multidisciplinary approach to the treatment of musculo-skeletal tumors].
AB  - Tumors of the musculoskeletal system are relatively rare. They occur mostly in
      the young, while in older age groups metastases and myeloma are more prevalent.
      Treatment has undergone major change in the past 20 years with the introduction
      of neoadjuvant treatment protocols. According to recent reports 5-year survival
      rates have increased from 20% to 60-70%. These new protocols involve the use of
      modern imaging modalities, immunohistochemical pathological analysis and improved
      surgical technics. This has required establishment of multidisciplinary teams of
      experts to escort the patient through all the steps of current treatment.

PMID- 9153933
TI  - [Prevalence rate, place of hospitalization and source of referral of complex
      nursing care patients in geriatric hospitalization].
AB  - For the past several years, the hospitalization and care of complex nursing care
      patients (CNCP) has caused concern among organizers, funders and care-givers of
      the geriatric hospitalization system (GHS). To assist in improving efficiency of
      the GHS and to address the lack of comprehensive, empirical and up-to-date
      information on these patients, we conducted a survey to characterize CNCP, to
      assess their medical problems and to determine their prevalence among the
      patients in GHS. The survey was conducted in 1994 using a day census. Data were
      collected on the 2,319 patients in geriatric beds in all the general hospitals
      and geriatric hospitals in Israel on the day of the survey. 28% of the patients
      in the GHS were CNCP and a quarter of them (7% of all patients) suffered from
      more than 1 medical condition. Tube feeding was the most prevalent condition (13%
      of all patients), followed by terminal illness (9%), deep pressure sores (7%) and
      intravenous transfusion for more than 3 days (6%). The 80% of the CNCP were
      hospitalized in geriatric hospitals, primarily in geriatric rehabilitation wards.
      Their average length of stay was over a year. Internal medicine wards of general
      hospitals were the most frequent source of patient referral. The survey's
      findings raise issues related to the organization of care of CNCP. They may serve
      as a basis for the reorganization of the geriatric hospitalization system in
      order to improve efficiency and quality of care for the benefit of patients,
      their families and services providers.

PMID- 9153932
TI  - [Epidemiologic characteristics of pediatric emergency room referral and
      hospitalization for diarrhea in the Negev].
AB  - Diarrheal diseases weigh heavily on the health of children, especially in
      developing countries, but also impose burdens on health care services worldwide.
      This study was performed to determine whether patterns of referrals in the Negev
      to the pediatric emergency room (PER) for diarrhea differ between the Jewish and
      Bedouin populations of the Negev, and the extent of the burden imposed on the PER
      and in-hospital services in the Negev. Characteristics of referrals and
      hospitalizations were examined from March 1994 to February 1995. Of the 27,834
      referrals to the PER for children under 16, 2518 (9%) had diarrhea and there were
      5,169 hospital admissions, 701 (13.6%). The annual rates of referral were 146 per
      10,000 in Jews and 225 in Bedouin, giving an odds ratio (OR) of 1.5 (p < 0.001).
      for Bedouin. The rates of hospitalization were 23 per 10,000 in Jews and 99 in
      Bedouin (OR 4.4, p < 0.001). 1380 (54.8%) of the PER referrals were of infants
      under a year of age. For hospitalization, the annual rates were 164 per 10,000 in
      Jews and 756 in Bedouin (OR 4.9, p < 0.001). During June to August referrals and
      hospitalizations for diarrhea were significantly higher, and from December to
      February significantly lower than during the remaining months. These differences
      arise from the marked seasonal pattern in the Bedouin population, whereas in the
      Jewish population there was no seasonal variation. Even in the 90's the burden on
      health services in the Negev as a result of diarrheal illness is considerable and
      the Bedouin population still contributes to that burden disproportionately. There
      is need both to reduce the gap in referrals and hospitalization between the
      populations, as well as to reduce the rates, using currently available means such
      as education, while developing new technologies, such as vaccines.

PMID- 9153934
TI  - [Superficial dorsal penile vein thrombosis (Mondor's disease)].
AB  - Superficial venous thrombosis of the chest wall was first described by Mondor in
      1939. Braun-Falco reported in 1955 superficial penile vein involvement in diffuse
      thrombophlebitis of the abdominal wall and in 1958 Helm and Hodge first described
      isolated superficial dorsal penile vein thrombosis. Since then, fewer than 50
      cases have been reported. The clinical presentation is usually redness and
      swelling of the dorsum of the penis, accompanied by a palpable, tender thrombotic
      vein. This acute and painful disease frightens the patients, who is concerned
      about his fertility and sexual function. The main cause of this disease is
      frequent sexual intercourse. Diagnosis is based upon anamnesis, physical
      examination and penile sonography with color Doppler imaging. It is usually a
      benign disease which resolves quickly under appropriate medical therapy. We
      present a man who was admitted for this condition and was successfully treated.

PMID- 9153935
TI  - [Glenoid fossa fracture].
AB  - 4 patients with displaced intra-articular glenoid fossa were treated either
      surgically or conservatively. After an average follow-up of 7 years, the clinical
      and radiographic results were satisfactory in all. The 2 treated surgically
      required shorter follow-up than those treated conservatively. Conservative
      treatment should be considered a good option for displaced intra-articular
      glenoid fossa fracture.

PMID- 9153936
TI  - [Salbutamol intoxication].
AB  - A 20-year-old asthmatic woman who ingested 300 mg of salbutamol (Albuterol) and
      30 g of paracetamol is presented. She had sinus tachycardia up to 160/min,
      hypotension (80/50 mmHg), tremor, hypokalemia (2.1 mEq/l) and hyperglycemia (12.1
      mEq/l). Treatment was by gastric lavage, fluids, potassium and N-acetylcysteine.
      Symptoms resolved in 24 hours.

PMID- 9153937
TI  - [Falling asleep at the wheel: chronicle of a predicatable accident].

PMID- 9153938
TI  - [Genetic therapy: reality and hopes].

PMID- 9153939
TI  - [Ocular manifestations of acquired immune deficiency syndrome].

PMID- 9153940
TI  - [Heat intolerance].

PMID- 9153941
TI  - [Vasculitis: classification, mechanisms, animal, models and treatment].

PMID- 9153942
TI  - [Impotence: doctor's dream, patient's nightmare].

PMID- 9153943
TI  - [Interstitial ectopic pregnancy: early diagnosis and management].

PMID- 9153944
TI  - [Use of student feedback by preclinical and clinical course directors].
AB  - We examined the conceptual and instrumental uses of student feedback on teaching
      by 2 preclinical and clinical course directors with authority to change structure
      and content of the courses, assess suitability of instructors and to change
      methods of teaching. Student feedback questionnaires have been collected
      systematically for over 2 decades. A report based on this feedback is sent to
      course directors, the dean, his assistants and the head of the curriculum
      committee. Course directors from both groups made broad use of the feedback but
      made greater use of the report than preclinical course directors. Students had
      greater regard for individual teaching by clinical course directors than by
      preclinical course coordinators. No relationship was found between the degree of
      use of feedback by members of either group and their level of teaching. We
      conclude that senior faculty use student feedback in their decisions regarding
      the structure and teaching methods of their courses and are not influenced by
      individual assessments, positive or negative, by their students.

PMID- 9153946
TI  - [Characteristics of hospitalized alcoholics].
AB  - The background characteristics of 1,173 alcoholics hospitalized for 3 months in
      this center during December 1982 to December 1994 were reviewed. Socio
      demographic variables and termination-of-treatment data, are described. The
      profile of the typical hospitalized alcoholic was that of a Jewish, urban,
      married, unemployed man, born in Asia-Africa (or in Israel) who had been living
      for many years in Israel and had many children and a low educational level. They
      usually start drinking in adolescence and come to the center after more than 15
      years of drinking, mainly at home and alone, and also have family relatives who
      drink. Implications of the data for treatment and for family physicians are
      presented.

PMID- 9153945
TI  - [Knowledge of adolescents about the fetal alcohol syndrome].
AB  - The level of knowledge of the risks of drinking during pregnancy in 175, 17-18
      years olds from kibbutzim in the eastern Upper Galilee was studied in January
      1996. This population had the highest rate of involvement with alcohol in Israel
      and had been involved in alcohol education activities in previous years. About
      53.71% of the sample believed that heavy drinking increases the risk of birth
      defects, but only 20.57% could correctly describe the fetal alcohol syndrome.

PMID- 9153947
TI  - [Blast injury: detonation and injury pattern].

PMID- 9153948
TI  - FasL expression on epithelial cells: the Bottazzo-Feldman hypothesis revisited.

PMID- 9153950
TI  - Pathogenesis and immunotherapy of autoimmune diseases.

PMID- 9153949
TI  - TCR signaling regulates thymic organization: lessons from TCR-transgenic mice.

PMID- 9153951
TI  - Unravelling the mast cell dilemma: culprit or victim of its generosity?

PMID- 9153952
TI  - A model of lymphocyte recirculation.

PMID- 9153953
TI  - Views on Vav.

PMID- 9153954
TI  - To 'B' or not to 'B' a germinal center?

PMID- 9153955
TI  - Cytokine regulation of endothelial cell function: from molecular level to the
      bedside.

PMID- 9153956
TI  - The role of FasL-induced apoptosis in immune privilege.

PMID- 9153957
TI  - T-cell regeneration: all repertoires are not created equal.

PMID- 9153958
TI  - Database screening for molecular mimicry.

PMID- 9153959
TI  - Also ...

PMID- 9153961
TI  - Hepatic stellate cells--from the viewpoint of retinoid handling and function of
      the extracellular matrix.
AB  - Hepatic stellate cells (vitamin A-storing cells, lipocytes, fat-storing cells,
      Ito cells) exist in the perisinusoidal space of the hepatic lobule, and store 80%
      of retinoids in the whole body as retinyl palmitate in lipid droplets in the
      cytoplasm. In physiological conditions, these cells play pivotal roles in the
      regulation of retinoid homeostasis; they express specific receptors for retinol
      binding protein (RBP), a binding protein specific for retinol, on their cell
      surface, and take up the complex of retinol and RBP by receptor-mediated
      endocytosis. By contrast, in pathological conditions such as liver fibrosis,
      these cells lose retinoids, and synthesize a large amount of extracellular matrix
      (ECM) components including collagen, proteoglycan and adhesive glycoproteins. The
      morphology of these cells also changes from the star-shaped stellate cells to
      that of fibroblasts or myofibroblasts. It is concluded that three-dimensional
      structure of the ECM components reversibly regulates the morphology,
      proliferation, and functions of the hepatic stellate cells.

PMID- 9153960
TI  - Reversible lymphocyte anergy during IL-2 therapy.

PMID- 9153962
TI  - [An attempt to clone genes which are related to neuronal target selection by the
      differential display].

PMID- 9153963
TI  - [Outline of historical view of human anatomy: Part 2].

PMID- 9153964
TI  - Death process of primitive erythrocytes and phagocytosis by liver macrophages of
      the mouse embryo.
AB  - Primitive erythrocytes from the yolk sac are nucleated cells which have a short
      life span of several days in the embryonic circulation of the mouse. The death
      process of primitive erythrocytes was ultrastructurally investigated in embryonic
      mice. At 12 days of gestation, primitive erythrocytes accounted for 96.1% of the
      circulating erythrocytes. The percentages in 13-, 14-, 15- and 18-day-embryos
      were 43.8%, 15.4%, 7.7% and 0.0%, respectively. Between 13 and 15 days, anucleate
      primitive erythrocytes made up from 1.5% to 5.9% of circulating erythrocytes.
      During the gestational period, the nuclei of primitive erythrocytes markedly
      decreased in volume, and the chromatin underwent condensation and marginated to
      crescents along the nuclear envelope. Following nuclear fragmentation and
      dissolution of condensed chromatin, nuclear residues were finally formed in aging
      primitive erythrocytes. Formation of annulate lamellae was also observed,
      associated with the nuclear shrinkage. The nuclei had an apoptotic-like
      appearance, but TUNEL-positive reactions could not be identified in any nuclei of
      the primitive erythrocytes. Dying erythrocytes with nuclear residues were
      phagocytosed in toto by hepatic macrophages and disposed of from embryonic
      circulation without enucleation.

PMID- 9153965
TI  - A variant branch of the internal laryngeal nerve supplying filaments to the
      cricothyroid muscle: an autopsy case.
AB  - We report a variant branch of the internal laryngeal nerve found in a Japanese
      male body. This branch, arising in the piriform fossa from the inferior portion
      of the loose network formed by the intercommunicating subbranches of the internal
      laryngeal nerve, descended in the interval between the thyroid and arytenoid
      cartilages accompanied by a branch of the superior laryngeal artery as far
      downward as the lowest portion of the thyroid cartilage. Here it crossed lateral
      to the inferior laryngeal nerve to which it gave off a communicating branch and
      reached the deep surface of the cricothyroid muscle. In this muscle it split into
      several divisions, each of which issued filaments to this muscle. The terminal
      branch of this variant branch ended in the fascia covering the cricothyroid
      muscle and the cricoid cartilage.

PMID- 9153966
TI  - [Predetermined epilations on the fixed areas of the face and forehead in a Tfm
      strain of mouse].
AB  - Many males and females with the bare skin area on their face were frequently
      observed in the Tfm strain of mouse representing testicular feminization. The
      predetermined epilation of oral and neighbouring hairs began at about ten months
      after birth and the subsequent bare skin area persisted for about 1 year to their
      death, but in some cases became expanded over the forehead. These facts indicate
      that this strain will be useful as a test animal for the detection if the effects
      of cosmetics and toiletry goods, medical drugs and so on. Microscopic examination
      of the epilation process revealed several morphological changes analogous to
      those in human male pattern baldness. However, in our case, several facts
      indicating that the androgens may stabilize hair growth, were discussed.

PMID- 9153967
TI  - A rare case: the medical cord of the brachial plexus sandwiched between the
      axillary and superficial brachial arteries.
AB  - We encountered a rare anomaly in the cadaver of a Japanese woman in the medical
      cord of the brachial plexus including the ulnar nerve and the medical root of the
      median nerve was sandwiched with the axillary and the superficial brachial
      arteries. The axillary artery passed inferior and dorsal to the medial cord,
      branching off the subscapular, anterior circumflex humeral arteries, and the
      common trunk of the posterior circumflex humeral and profunda brachii arteries,
      and ended as the inferior ulnar collateral artery. The superficial brachial
      artery descended ventral to the median nerve and divided into the radial and
      ulnar arteries in the cubital fossa. We discuss the developmental formation of
      this anomaly.

PMID- 9153968
TI  - Experimental studies on modified human ureter as an arterial substitution for
      reconstruction of small caliber vessels.
AB  - Human ureters were experimentally employed as vascular biografts for small
      caliber vessels. They were produced by tanning with polyepoxy compound or
      glutaraldehyde, and also were compared with saphenous veins tanned by polyepoxy
      compound and/or ready-made vascular graft of polytetrafluoroethylene (e-PTFE).
      These produced grafts, which had enough elasticity and excellent durability were
      successfully implanted to the carotid arteries in Japanese white rabbits. The
      grafts were sacrificed after 1 month observation. In this model there were no
      evidence of rejection, aneurysmal formation and/or infection. Polyepoxy compound
      fixed human ureter (n = 6), polyepoxy compound fixed saphenous vein (n = 6) and e
      PTFE (n =3) showed good patency, but all glutaraldehyde fixed human ureters (n =
      3) were completely occluded with severe intimal hyperplasia. Especially,
      polyepoxy compound fixed human ureter showed excellent patency as well as
      function, and the histological findings revealed monolayer endothelial cells
      covering the surface of the graft. No intimal hyperplasia was demonstrated at the
      anastomotic site. This study suggested that the polyepoxy compound fixed human
      ureter could serve as a satisfactory blood conduit of reconstruction for the
      small caliber vessels. Our preliminary data also suggests that longer observation
      up to 6 months in polyepoxy compound fixed human ureter graft and 18 months in
      polyepoxy compound fixed saphenous vein graft after surgery, arteriovenous shunt
      (A-V shunt), long bypass with a graft length of 2 to 5 cm), Y-graft model,
      sequential model and reinforcement graft by dacron cloth give good results.

PMID- 9153969
TI  - Exercise performance after PTMC in mitral stenosis: the relation with
      hemodynamics, ventilatory response and skeletal muscle function.
AB  - We examined the contribution of hemodynamics, ventilatory response and skeletal
      muscle function to the exercise performance after percutaneous transvenous mitral
      commissurotomy (PTMC). Nine patients with mitral stenosis (MS) underwent symptom
      limited maximal ergometer exercise before, at 1 week and 3 months after PTMC. At
      3 months after PTMC four patients (group 1) revealed an improved exercise
      performance (peak oxygen uptake (VO2) 747 +/- 145 to 1,039 +/- 175 ml/min; p <
      0.01), and five patients (group 2) showed an unchanged exercise performance.
      Exercise performance in group 1 already increased at 1 week after PTMC. Peak
      cardiac output (Q) in group 1 increased (4.9 +/- 0.7 to 6.9 +/- 1.0 L/min, p <
      0.05) at 3 months after PTMC. The slope of the minute ventilation (VE)-carbon
      dioxide production (VCO2) relation during exercise decreased at 1 week after PTMC
      (40.2 +/- 4.2 to 30.5 +/- 3.8, p < 0.05), and decreased slope of VE-VCO2 remained
      at 3 months after PTMC. However in group 2 these parameters did not change. There
      was a significant correlation between percent change of peak VO2 and percent
      change of peak Q from before to 3 months after PTMC (r = 0.84, p < 0.01). However
      there were no differences in reduction of mean pulmonary artery pressure,
      pulmonary vascular resistance and maximum isometric force (MIF) of left
      quadriceps between two groups. These findings suggest that the increased Q and
      improved excessive ventilation were important for increase in exercise
      performance in patients with MS after PTMC.

PMID- 9153970
TI  - Adult T cell leukemia presenting as multiple submucosal tumors of the intestine:
      detection of HTLV-I DNA by polymerase chain reaction.
AB  - We discuss a 45-year-old man who presented with ileus due to multiple submucosal
      tumors of the small and large intestines. Emergency operation was performed and
      histological examination of the tumors revealed pleomorphic cells with
      helper/inducer T-cell phenotype. Polymerase chain reaction (PCR) analysis using
      DNA extracted from the paraffin-embedded material showed that the intestinal,
      jejunal and femoral lymphoma samples contained human T-cell leukemia virus type-I
      (HTLV-I) DNA. Although no atypical lymphocytes were found in the peripheral
      blood, a diagnosis of adult T-cell leukemia was made. The PCR analysis of HTLV-I
      infection using paraffin-embedded materials seems to be useful when we
      encountered patients with T-cell lymphoma in the gastrointestinal tract.

PMID- 9153971
TI  - A study of patients having survived curative operation for esophageal cancer for
      five years or more.
AB  - In order to analyze the prognostic factors for curatively resected esophageal
      cancer, 42 patients who had survived their operation more than 5 years (long-term
      survivors) were compared for clinicopathologic items with 30 recurrent patients
      who had died within 5 years postoperatively (recurrent cases). Moreover, to
      estimate the prognosis for the current survivors, we investigated the cause of
      death of long-term survivors who had died. This comparison showed that the rate
      of lymphatic invasion was 36.4% and of blood vessel invasion 19.4% for the
      survivors, much lower than those of the recurrent cases which were respectively
      62.1% and 31.0%. It was found that the significantly unfavorable prognosis
      determinant factors was lymphatic invasion (p < 0.05). Ten out of 12 n (+)
      survivors (83.3%) had single metastasing region, one in the neck, three in the
      mediastinum and six in the abdomen. This was not significantly different from the
      recurrent cases, of whom, ten out of 14 n (+) cases had a single metastasing
      region, six in in the mediastinum and four in the abdomen. As for the number of
      metastatic lymph nodes, nine out of 12 n (+) survivors (75%) had only one
      matastatic lymph node, and none of them had more than three. On the other hand,
      two of the recurrent cases had more than three. Of the 42 long-term survivors, 21
      patients are still alive (current survivors' average age: 70.1 +/- 7.9) and 21
      have died. The cause of death was recurrence in six cases, metachronous primary
      malignant tumor in three, other disease in six and unknown in six. The average
      age of death was 62.1 +/- 10.3 in cases of recurrence or double cancer, and 71.8
      +/- 9.5 in others. The former were thus significantly younger than the latter (p
      < 0.05).

PMID- 9153972
TI  - Augmentation of parasympathetic nerve function in patients with extrinsic
      bronchial asthma--evaluation by coefficiency of variance of R-R interval with
      modified long-term ECG monitoring system.
AB  - Patients with bronchial asthma (BA) have evidence of increased vagal cholinergic
      tone. Although the cardiovascular-respiratory tests used in the past might have
      been biased by concomitant chest disease, coefficiencies of variance of the R
      wave to R wave (RR) interval (CVR-R) on electrocardiogram (ECG) have been applied
      to many diseases as a method of functional evaluation of the parasympathetic
      nerve system. In 24 hour recordings of ECG (Holter ECG), continuous values of CVR
      R have been determined for each one-minute period with a recently developed long
      term ECG monitoring system. To examine functional augmentation of parasympathetic
      nerve in patients with BA, we applied this system in the present study to
      determine the alteration of parasympathetic nerve function during an inhaled
      methacholine provocation test in 14 patients and 7 healthy subjects. CVR-R values
      were calculated from the collection of a 24-hour electrocardiogram. Bronchial
      response, which was measured by methacholine inhalation, was evaluated with the
      baseline value of respiratory resistance (Rrs-cont), the cumulative dose
      producing a 35% decrease in respiratory conductance (PD35Grs) and the minimum
      cumulative dose required to start to decrease respiratory conductance from
      baseline (Dmin). The serum concentrations of epinephrine and norepinephrine were
      measured at the basal and double-increased levels of respiratory resistance
      during the inhalation test. The increased values of CV(R-R) in asthmatic patients
      were intimately associated with augmented respiratory resistance. The disparity
      of CV(R-R) values (delta CV) during the resistance levels from basal to double in
      the asthmatic group was significantly greater than that in the control group. The
      absolute change of CV(R-R) values in the asthmatic group was significantly larger
      than that in the control group. There was a significant correlation between delta
      CV and Dmin (r = 0.536, p < 0.05), and between delta CV and PD35Grs (r = 0.552, p
      < 0.05). The serum concentrations of epinephrine and norepinephrine were not
      significantly different during the methacholine inhalation provocation test. We
      conclude that alteration of the values of CV(R-R), which were calculated with a
      modified long-term ECG recording system, may reflect the change of
      parasympathetic nerve function and the severity of bronchial hyperreactivity, and
      this system can be a useful non-invasive method for evaluation of increased vagal
      tone in patients with bronchial asthma.

PMID- 9153973
TI  - The effect of lipid peroxide on osteoblasts and vascular endothelial cells--the
      possible role of ischemia-reperfusion in the progression of avascular necrosis of
      the femoral head.
AB  - Many patients undergo operations of the hip joint for avascular necrosis of the
      femoral head (ANF). Abnormal lipid metabolism in thought to play a certain role
      in the pathogenesis of ANF. In the present study we have detected the abnormal
      lipid from the necrotic area of the femoral heads suffering from ANF by gas
      chromatography-mass spectrometry (GC/MS). This abnormal lipid was supposed to be
      cholesterol epoxide, because its peak was observed at one oxygen molecular weight
      larger position than that of cholesterol. However, this abnormal lipid was not
      found in the femoral heads with osteoarthritis (OA). We also investigated the
      effect of the lipids (cholesterol and cholesterol epoxide) and corticosteroid
      (prednisolone) on proliferation of osteoblastic cell line (MC3T3-E1) cells and
      vascular endothelial cells (EC) derived from human umbilical vein using 3H
      thymidine (3H-TdR) incorporation. Cholesterol has no effect on osteoblast
      proliferation up to 100 micrograms/ml, while cholesterol epoxide inhibited the 3H
      TdR incorporation in a dose dependent fashion and a significant suppression was
      attained at the concentration of 10 micrograms/ml. In contrast, both cholesterol
      and cholesterol epoxide had suppressive effect on the EC proliferation. DNA
      synthesis of the osteoblasts was suppressed by prednisolone and additive
      inhibitory effect was observed in the combination of cholesterol epoxide and
      prednisolone. None of the free radical scavengers such as mannitol,
      dimethylsulfoxide (DMSO), super oxide dismutase (SOD) and catalase had
      significant recovery effect on the suppressed 3H-TdR incorporation of both MC3T3
      E1 cells and EC. Only alpha-tocopherol restored the suppressed incorporation of
      3H-TdR. These results suggest that lipid peroxide has an important role in the
      progression of ANF by suppressing the proliferation of osteoblasts and EC.

PMID- 9153974
TI  - Doses of solar ultraviolet radiation correlate with skin cancer rates in Japan.
AB  - We analyzed trends in the disease rate of skin cancers in the 1976-80 and 1986-90
      intervals in the 27 university hospitals in Japan. We also measured doses of
      solar ultraviolet (UV) radiation at Sapporo, Kobe and Miyazaki to evaluate the
      relationship between the two in Japan. The rates of basal cell carcinoma (BCC)
      and actinic keratosis (AK) were higher in 1986-90 than in 1976-80, whereas the
      rate of squamous cell carcinoma (SCC) was lower in 1986-90 than in the earlier
      period. The rates of SCC, BCC and AK in the southern part of Japan were about
      five times higher than those in the north, and the average daily UV dose measured
      with a Robertson-Berger meter in 1995 was about 1.8 times higher in Miyazaki than
      in Kobe. That measured by MS-210D UV dosimeter in Sapporo was about 0.53 times
      lower than in Kobe. These results demonstrate that solar UV dose is higher in the
      southern part of Japan than that in the northern part, explaining the higher rate
      of non-melanoma skin cancer in southern part of Japan. A significant increase of
      AK and BCC may reflect the trend of UV increase in Japan.

PMID- 9153975
TI  - A new simplified method for laser sinus node modification without
      electrophysiological technique.
AB  - As the treatment of inappropriate sinus tachycardia, beta-adrenoreceptor blockade
      therapy is the most common method for pharmacological heart rate control, but it
      is occasionally limited by side effects of the drugs, especially in patients with
      cardiac dysfunction. On the other hand, cryoablation or surgical exclusion of the
      sinus node have not been accepted generally for their necessity of permanent
      pacemaker implantation. Modification of the sinus node function is a new method
      of nonpharmacological treatments, although the skillfull and troublesome
      technique is required. In this study, the efficacy and safety of laser sinus node
      modification without electrophysiological technique were investigated as a new
      simplified method. In six mongrel dogs, the laser-tissue interactions by
      epicardial Nd-YAG laser irradiation were investigated by measuring the diameter
      and the depth of the irradiated lesions. Laser irradiations were performed from
      the head to the tail on the sinus node areas directed only by terminal groove for
      the visual landmark without electrophysiological technique until about 25%
      decrease in heart rate occurred in other six open-chest dogs.

PMID- 9153976
TI  - Failure to breathe at birth.

PMID- 9153977
TI  - Clinical epidemiology: the expanding mandate.

PMID- 9153978
TI  - Correlates of mortality among hospital-born neonates with birth asphyxia.
AB  - BACKGROUND: Birth asphyxia is a major cause of neonatal mortality. An
      understanding of the determinants of mortality among asphyxiated neonates will
      help formulate effective management protocols. METHODS: One hundred and fifty
      consecutive neonates with birth asphyxia (apnoea or gasping respiration at 1
      minute of age) were prospectively studied. The association of the outcome
      variable, namely, mortality before discharge, was documented in relation to a
      number of clinically important risk factors. RESULTS: The neonatal mortality of
      24.7% (37/150) among asphyxiated neonates was 34.5-times compared to that of the
      non-asphyxiated population (p < 0.001). The mortality rates in preterm-and term
      asphyxiated neonates were 47.8% and 6%, respectively (p < 0.0001). The relative
      risk of mortality increased progressively with increased birth-weight. On
      univariate analysis, prematurity, low birth-weight, respiratory distress,
      severity of asphyxia, hypoxic-ischaemic encephalopathy, apnoea, acidosis and
      seizures were found to be significant risk factors of death. However, on step
      wise regression analysis, prematurity emerged as the most significant determinant
      of mortality. The highest positive predictive value (58.3%) for mortality was
      documented for hypoxic-ischaemic encephalopathy. CONCLUSION: A significant
      reduction in mortality among asphyxiated neonates will require aggressive
      management of prematurity-related neonatal complications and hypoxic-ischaemic
      encephalopathy.

PMID- 9153979
TI  - The 13C urea breath test to assess Helicobacter pylori infection in school
      children.
AB  - BACKGROUND: The 13C urea breath test was used in this study to establish it as a
      diagnostic tool as well as to assess the prevalence of Helicobactor pylori in a
      group of school children. METHODS AND RESULTS: In a group of 50 children studied,
      82% were found to be positive for H. pylori by this test. The influence of diet
      in modifying the results of the test was also assessed. Relatively small errors
      were seen if adequate precautions were taken. CONCLUSION: Epidemiological studies
      are required to further quantify the magnitude of the prevalence of H. pylori in
      the Indian setting.

PMID- 9153980
TI  - In vitro activity of netilmicin against clinical isolates of methicillin
      resistant and susceptible Staphylococcus aureus.
AB  - BACKGROUND: The emergence of methicillin-resistant Staphylococcus aureus and its
      multidrug-resistant property has led to the search for an effective antibiotic to
      combat staphylococcal sepsis. At present, vancomycin remains the most effective
      antibiotic. This study evaluated the in vitro efficacy of netilmicin (an
      aminoglycoside) and compared its activity with 4 other antibiotics, viz.
      vancomycin, amikacin, tobramycin and ofloxacin. METHODS: The minimum inhibitory
      concentration of the antibiotics was determined by the agar dilution method.
      Thirty strains each of methicillin-resistant and -susceptible S. aureus isolated
      from pus and blood cultures were included. RESULTS: The susceptibility to
      netilmicin was found to be 100% and was the same as that observed for vancomycin.
      CONCLUSION: All the methicillin-resistant S. aureus strains tested showed 100%
      susceptibility to netilmicin, suggesting its use in patients with such infections
      as an alternative to vancomycin. However, this finding needs to be verified in
      the clinical setting.

PMID- 9153981
TI  - Aetiology of severe vitamin A deficiency in children.
AB  - BACKGROUND: Severe forms of vitamin A deficiency or keratomalacia are common in
      young children. Keratomalacia is thought to be associated with malnutrition due
      to poor weaning practices and manifests at 3 to 4 years of age. As survival rates
      for infants have increased, keratomalacia is being seen in children less than 6
      months of age. Hence, keratomalacia shows two peaks--one in early infancy and the
      other in the toddler or pre-school age groups. However, the reasons for its
      occurrence at these ages may be different. METHODS: Records of children admitted
      to the Nutrition Rehabilitation Centre at the Government Rajaji Hospital during
      1971-89 and at the Aravind Children's Hospital during 1991-93 were reviewed for
      severity of vitamin A deficiency associated with protein-energy malnutrition.
      Records of 1990 were not available. RESULTS: During 1971-89, 4691 children were
      admitted to the Nutrition Rehabilitation Centre for Nutritional rehabilitation
      and treatment of vitamin A deficiency. Of these, 1575 (33.6%) children had
      corneal involvement due to vitamin A deficiency. During 1991-93, 7439 children in
      the age group of 0-15 years were seen at the Aravind Children's Hospital--185 had
      vitamin A deficiency; 133 were below the age of 5 years and 69 had keratomalacia.
      Fifteen children with keratomalacia were below the age of one year and 12 were
      below 6 months of age. CONCLUSION: The incidence of severe vitamin A deficiency
      of keratomalacia shows two peaks; one in early infancy (< 6 months) and the other
      in the pre-school age group. The first peak is probably related to maternal
      nutrition and decreased breast-feeding while the second peak is possibly related
      to poor weaning practices.

PMID- 9153982
TI  - Increasing toxoplasma seropositivity in women with bad obstetric history and in
      newborns.
AB  - BACKGROUND: Most infants with congenital Toxoplasma gondii infection have no
      symptoms at birth but few may develop retinal diseases or neurological
      abnormalities later in life. The presence of significant titres of antitoxoplasma
      antibodies in women in the reproductive age group indirectly indicates that
      Toxoplasma gondii is the cause of such congenital abnormalities and also sporadic
      abortions in some women. METHODS: We did a retrospective analysis of
      antitoxoplasma antibodies detected by indirect haemagglutination assay, in women
      with bad obstetrical history and in newborns clinically suspected of congenital
      toxoplasmosis during 1981-91. RESULTS: A significant increase in seropositivity
      in women and newborns was seen during 1989-91 as compared to 1981-88. More
      seropositive patients were recorded between April-June and October-December.
      However, no significant correlation could be observed between rising incidence of
      seropositivity and the seasonal distribution or age of women. CONCLUSION:
      Epidemiological studies are required to ascertain the reason for the increasing
      trend of toxoplasma seropositivity and to suggest appropriate control strategies
      as it is possible to prevent congenital infection.

PMID- 9153983
TI  - Intestinal geohelminthiasis in the developing world.
AB  - Intestinal parasitic helminths such as roundworms (Ascaris lumbricoides),
      hookworms (Ancylostoma doudenale and Necator americanus) and whipworm (Trichuris
      trichiura) are common in the developing world. Strongyloides stercoralis, though
      not so common, also contributes to health problems. The prevalence of intestinal
      worm infestation in India varies from 5% to 76%, which is similar to that in
      other developing countries. These parasitic infestations are acquired by
      ingestion, inhalation or penetration of the skin by the infective forms. Ascaris
      causes many intestinal and respiratory symptoms and plays an important role in
      precipitating protein-energy malnutrition in undernourished children. Hookworms
      cause anaemia and hypoproteinaemia. In areas where hookworm infestation is
      endemic, 90% of pregnant mothers are anaemic. Trichuriasis as a causative agent
      of human disease has only recently gained attention. Heavy infestation with T.
      trichiura can result in severe colitis and significant blood loss. This in turn
      can lead to impaired cognitive functions which are reversible on treatment.
      Though not as widely prevalent as the other geohelminths in India, Strongyloides
      stercoralis infestation can be fatal in debilitated and immunosuppressed
      children. So far, the impact of these parasites on the health of children has
      been underestimated and concentrated efforts to minimize the worm load and its
      consequences have not been given due importance in our health policies. This
      article reviews the pathophysiology, clinical impact and control options of the
      most commonly prevalent geohelminths in the developing world.

PMID- 9153984
TI  - Gemcitabine: a ray of hope for pancreatic cancer?

PMID- 9153985
TI  - Quinapril for coronary artery disease.

PMID- 9153986
TI  - Cigarette smoking in China--a message for India.

PMID- 9153987
TI  - Depression.

PMID- 9153989
TI  - 'Health-for-All' in the twenty-first century: a global perspective.
AB  - Changes in the broad determinants of health since the Alma Ata Conference in 1978
      necessitate a renewed examination of the underlying principles and focus of the
      Primary Health Care (PHC) strategy. The PHC approach has been adopted by most
      countries and has led to improved access to certain basic health services.
      However, the health gains in other areas are less encouraging. Some elements of
      the PHC approach, for example, the effective implementation of equity-oriented
      health policies and the need to improve management principles within health
      services, have yet to be fully implemented. Moreover, to address the underlying
      determinants of health status, the World Health Organization's (WHO) renewed
      global health policy will have to include certain issues that were not considered
      at Alma Ata. For example, the health impacts of global recession and
      globalization and the need for human-centered sustainable development strategies
      were not considered at Alma Ata. A renewed global health policy will also have to
      consider demographic, epidemiological, environmental and technological changes
      that have emerged since 1978. It is important that WHO's renewed policy be based
      on sound evidence, a commitment to ethical principles and broad use of
      partnerships for health at global, national and local levels. One implication of
      this new context of health development for the renewed health policy will be that
      'thinking globally and acting locally' will have to complemented by stronger
      global action to protect local and national health.

PMID- 9153990
TI  - A response to bereavement.

PMID- 9153988
TI  - Incorporation of emergency medicine in the undergraduate curriculum.
AB  - BACKGROUND: Emergency medicine has been recognized as a specialty in western
      countries. However, in India, most hospitals and medical colleges have no
      provision for teaching this specialty. This study was done to assess the
      feasibility of incorporating emergency medicine in the undergraduate medical
      curriculum. METHODS: Sixty final year undergraduate students underwent a special
      training programme in emergency medicine. A feedback was obtained from the
      students. RESULTS: While the practical experience was rated above satisfactory by
      65% of them, 98.2% of them appreciated the lecture sessions. Overall, the
      programme was rated as more than good by 92.7%. CONCLUSION: As a specialty that
      emphasizes basic clinical skills, emergency medicine should be incorporated in
      the undergraduate medical curriculum.

PMID- 9153991
TI  - Health care utilization.

PMID- 9153992
TI  - What does he of medicine know, who only medicine knows?

PMID- 9153993
TI  - Ammonium salt of glycyrrhizic acid as an antiviral.

PMID- 9153994
TI  - [Erythrocyte-induced "torsade de pointes" ventricular tachycardia].
AB  - A case of erythromycin-induced acquired long QT syndrome and "torsades de
      pointes" ventricular tachycardia is reported. The peculiar ventricular
      tachyarrhythmia was evoked by orally administered erythromycin (1.5 g/die) in the
      presence of diuretic (clopamide)-induced hypokalaemia. The pause-dependent
      "torsades de pointes" was preceded by prolonged QTU interval (560 ms),
      "particular bigeminy" and "short-long-short" RR interval sequence. The recurrent
      ventricular tachycardia causing syncopal attacks was abolished by the
      discontinuation of erythromycin treatment, K+/Mg(2+)-supplementation and oral
      mexiletine therapy. It is emphasized that the macrolide antibiotic/prokinetic
      erythromycin, applied in therapeutic dosages, blocks the rapidly activating
      delayed rectifier potassium current (IKr), and as such, prolongs ventricular
      repolarization and may be "torsadogenic".

PMID- 9153995
TI  - Murine Polycomb- and trithorax-group genes regulate homeotic pathways and beyond.

PMID- 9153996
TI  - Polycomb in plants.

PMID- 9153998
TI  - Biologists and mathematicians: bridging the chasm.

PMID- 9153997
TI  - Why map the rat?

PMID- 9153999
TI  - The intertwining of plant development and evolutionary mechanisms.

PMID- 9154000
TI  - FGFR activation in skeletal disorders: too much of a good thing.
AB  - During the past two years, a growing number of mutations have been identified in
      three of the four members of the fibroblast growth factor receptor (FGFR) family
      as causing autosomal dominant disorders of skeletal and cranial development.
      These mutations map to the extracellular domain, the transmembrane domain, or the
      tyrosine kinase domain of these receptors. Recent studies demonstrate that a
      common mechanism, constitutive activation of receptors signaling, underlies most,
      if not all, of these disorders. This suggests a normal role for FGFRs in the
      negative regulation of bone growth.

PMID- 9154001
TI  - Zebrafish genomics: from mutants to genes.
AB  - Exquisite embryonic lethal mutations have been isolated in hundreds of genes
      necessary for zebrafish development. Analysis of this resource promises to
      enhance our understanding of the molecular genetic mechanisms of vertebrate
      development. This review discusses the state of the zebrafish genome project and
      the genetic trickery that can expedite molecular isolation of genes disrupted by
      these mutations.

PMID- 9154002
TI  - A thousand and one roles for the Drosophila EGF receptor.
AB  - In the Drosophila genome there is a single member of the EGF receptor tyrosine
      kinase family. This receptor fulfills multiple roles during development, as
      reflected by the many designations given to mutant alleles in the locus (Egfr,
      DER, faint little ball, torpedo and Ellipse). The full scope of EGFR functions
      became apparent only in recent years: receptor activation was shown to have an
      instructive role in successive cell fate determination events during oogenesis,
      embryogenesis, and the proliferation and differentiation of imaginal discs. To
      ensure the fidelity of these processes, the precise place and time of receptor
      activation are tightly regulated by the localized presentation of activating
      ligands, in conjunction with a negative-feedback loop generated by an inhibitory
      secreted factor. The cellular mechanisms that translate EGFR activation to
      discrete cell fates are now the focus of intense studies.

PMID- 9154003
TI  - What restricts the activity of mariner-like transposable elements.
AB  - A number of mechanisms have recently been described that might be important in
      restricting the level of activity of mariner-like transposable elements (MLEs) in
      natural populations. These mechanisms include overproduction inhibition, in which
      increasing the dose of transposase decreases net activity. Another mechanism is
      mediated by certain missense mutations, in which a mutant transposase protein
      impairs the activity of the wild-type transposase in heterozygous
      mutant/nonmutant genotypes. A further mechanism is the potential for transposase
      titration by defective elements that retain transposase binding activity. The
      issue of regulation is not only of theoretical importance in understanding the
      molecular and evolutionary genetics of MLEs, but also of practical significance
      in learning how best to use MLEs in the germline transformation of insect pests
      and disease vectors.

PMID- 9154004
TI  - Studies on inherited cancers: outcomes and challenges of 25 years.
AB  - Research on the dominantly inherited cancer-susceptibility syndromes over the
      past 25 years has defined the genetic basis of most of these diseases, usually
      through linkage analysis on families carrying the disease, and identification and
      analysis of the genes responsible. At present, almost all of these genes have
      been cloned and, in most cases, the findings have lent full support to Knudson's
      original hypothesis: germline carriers of mutations in cancer susceptibility
      genes are predisposed to developing cancer, the resultant tumours contain
      aberrations in the remaining copy of that gene, and these genes often play a
      pivotal role in the genesis of the equivalent sporadic cancers, whereby two
      somatic events result in the disruption of both copies of the gene. This
      perspective highlight some of the issues that have been raised by these studies,
      and points to a few of the areas of future research that might help to resolve
      them.

PMID- 9154005
TI  - Views of RNA on the World Wide Web.

PMID- 9154006
TI  - Monolingual and bilingual children's use of the mutual exclusivity constraint.
AB  - The use of the mutual exclusivity constraint was examined in three-year-old and
      six-year-old children who were either monolingual in English (N = 32) or
      bilingual in English/Urdu (N = 32) or in English/Greek (N = 32). Three tests of
      the constraint were used: disambiguation rejection, and restriction. On the
      disambiguation test, the mutual exclusivity bias was significantly more evident
      in five- and six-year-old monolingual children than in their same-age bilingual
      peers. Monolingual children were also more likely than bilingual children to
      reject a new name for a familiar object. However, using a restriction test,
      neither monolingual nor bilingual children readily accepted and restricted
      typical names for hybrid objects. Developmental differences were also found, as
      older (five- to six-year-old) monolingual children's responses on the tests were
      generally more consistent with the constraint than younger (three- to four-year
      old) children's responses. Nevertheless, bilingual children did use the
      constraint, but not to the extent of monolingual children.

PMID- 9154007
TI  - When is it best to hear a verb? The effects of the timing and focus of verb
      models on children's learning of verbs.
AB  - This paper explores the effects of certain aspects of verb input on verb
      acquisition. It has been observed that the timing of a verb model affects
      children's learning of the verb (Tomasello & Kruger, 1992). It has also been
      observed that the focus of the event to which the verb refers affects the
      argument structure children assign to the verb (Pinker, 1989). This experiment
      investigated the interaction between the timing of verb models and the focus of
      the events to which they refer. Thirty children aged from 2;3 to 3;6 heard two
      novel verbs, one movement focused and the other result focused. Half heard the
      verbs before the event (impending condition) and half after it (completed
      condition). An interaction of verb timing and verb focus was found. The movement
      verb was learned better in the impending condition and the result verb in the
      completed condition. The contribution of this finding to our understanding of the
      processes involved in verb acquisition is considered.

PMID- 9154008
TI  - Children's acquisition of speech timing in English: a comparative study of voice
      onset time and final syllable vowel lengthening.
AB  - This study describes English-speaking children's acquisition of voice onset time
      (VOT), a segmental feature that specifies the timing of word-initial stop
      consonants, and final-syllable vowel lengthening (FSVL), a suprasegmental feature
      that influences the timing of vowels. The purpose of this study was to evaluate
      two hypotheses about the acquisition of speech timing contrasts; a 'motoric'
      hypothesis predicting that children would control the vowel duration contrast
      earlier than the consonantal one (FSVL before VOT), and a 'representation'
      hypothesis predicting that children would control the contrast represented on the
      segmental level of linguistic description earlier than the contrast represented
      on the suprasegmental level (VOT before FSVL). Longitudinal acquisition patterns
      for both contrasts were compared in ten children between the mean ages of 1;6 and
      2;0. The results, indicating that English-speaking children usually acquired VOT
      before FSVL, are discussed in light of evidence that French-speaking children
      acquire analogous contrasts in the opposite sequence. The crosslanguage
      comparisons support limited forms of both the motoric and representation
      hypotheses. As promising topics for further study, the results also suggested the
      importance of individual differences, and the variability of timing features in
      the input.

PMID- 9154009
TI  - Young children's understanding of the cognitive verb forget.
AB  - Investigation of children's understanding of the cognitive verb forget has shown
      that young children do not consider the role of prior knowledge when using this
      verb. Thus, someone may be said to have forgotten a fact despite not ever having
      previously known it. However, forget can also be used to refer to a failure to
      recall a prior intention. Three experiments examined the role of prior intention
      as well as prior knowledge in the comprehension of forget by 160 young children
      aged four to eight years. The results showed that children initially have two
      interpretations of forget: as an unfulfilled desire rather than a failure to
      recall a prior intention, and as a state of not knowing rather than a failure to
      recall prior knowledge. Explanations for the late comprehension of forget are
      discussed in terms of representation of knowledge and intention, processing
      capacity and exposure to pragmatic usages.

PMID- 9154010
TI  - The interaction of language and thought in children's language acquisition: a
      crosslinguistic study.
AB  - The purpose of this research was to investigate the potential interaction of
      conceptual representations and linguistic systems in the process of language
      acquisition. Language-thought interactions were studied in 80 American, 48
      Finnish and 48 Polish preschool children. The research focused on the conceptual
      and linguistic development of space and time. The spatial and temporal conceptual
      tasks were designed to measure the transition from experimental to inferential
      knowledge of space/time representations. In the linguistic domain, comprehension
      and production tests were used to evaluate the children's capacity to understand
      mono- and bi-referential location in space and time, where mono-referential
      location involves a single referent object/event with intrinsic properties (e.g.
      in/on or past/non-past), and bi-referential location requires two or more
      referent objects/events and relative perspective (e.g. deictic front/back or
      before/after). The conceptual and linguistic tests revealed significant changes
      during the period from two to five years of age, and measures of conceptual
      development were correlated with measures of linguistic development. As spatial
      and temporal representations became more structured, children were able to move
      from mono- to bi-referential location. In a comprehension test, we discovered an
      interaction of language by dimension. Finnish children found spatial distinctions
      relatively easy and Polish children found temporal distinctions relatively easy.
      This interaction was expected on the basis of the relative complexity of the
      morpho-syntactic coding in the spatial and temporal systems of the two languages.
      However, the argument relating the timing of acquisition to the transparency
      versus opacity of the linguistic systems was not supported by the English
      language comparison. Finally, the Finnish children were relatively better able to
      accomplish the spatial conceptual tasks as compared to the Polish children. This
      finding is consistent with a developmental concept of linguistic relativity. In
      general, the research indicates that spatial and temporal linguistic systems and
      representational knowledge interact during development with the influence
      occurring in both directions.

PMID- 9154011
TI  - The differential effect of storybook reading on preschoolers' acquisition of
      expressive and receptive vocabulary.
AB  - The present study was conducted to assess the effect of didactic techniques used
      during storybook reading on young children's acquisition of new vocabulary
      introduced in storybooks. Thirty children for each group of three- and four-year
      old children were read one storybook individually. The study included three
      storybook reading conditions: single-reading, repeated-reading and questioning.
      In both the repeated-reading and the questioning conditions, the storybook was
      read three times. Children in the questioning condition were asked, during each
      reading of the storybook, to label target items with the novel words. Listening
      to multiple readings of a storybook facilitated children's acquisition of
      expressive and receptive vocabulary, whereas answering questions during the
      multiple readings was more helpful to the acquisition of expressive than
      receptive vocabulary. These findings suggest that, under certain conditions,
      didactic techniques used by adults have differential effects on preschoolers'
      receptive and expressive vocabulary.

PMID- 9154012
TI  - The Contrast Theory of negative input.
AB  - Beliefs about whether or not children receive corrective input for grammatical
      errors depend crucially on how one defines the concept of correction. Arguably,
      previous conceptualizations do not provide a viable basis for empirical research
      (Gold, 1967; Brown & Hanlon, 1970; Hirsh-Pasek, Treiman & Schneiderman, 1984).
      Within the Contrast Theory of negative input, an alternative definition of
      negative evidence is offered, based on the idea that the unique discourse
      structure created in the juxtaposition of child error and adult correct form can
      reveal to the child the contrast, or conflict, between the two forms, and hence
      provide a basis for rejecting the erroneous form. A within-subjects experimental
      design was implemented for 36 children (mean age 5;0), in order to compare the
      immediate effects of negative evidence with those of positive input, on the
      acquisition of six novel irregular past tense forms. Children reproduced the
      correct irregular model more often, and persisted with fewer errors, following
      negative evidence rather than positive input.

PMID- 9154013
TI  - Comprehending compounds: evidence for metaphoric skill?
AB  - Previous studies of children's comprehension of compound nouns show that three
      year-olds can identify the appropriate referent for a compound when shown picture
      arrays that include salient distractors. The four studies presented here
      investigate comprehension of one kind of compound, metaphoric compounds (i.e.
      noun-noun compounds in which one noun expresses similarity to another object, as
      in catfish). Forty-four three-year-olds, 45 five-year-olds and 22 adults were
      shown a series of picture arrays and were asked to identify referents of various
      types of metaphoric compounds. The arrays included target pictures that had
      metaphoric resemblances based on shape (e.g. bug shaped like a stick) or on
      colour/pattern (e.g. shells with black and white stripes, like a zebra). Results
      showed that three- and five-year-olds can comprehend a shape-based metaphoric
      compounds such as stick-bug, even when faced with salient distractors (e.g. a
      stick, a bug next to a stick). The younger children had some difficulty with
      colour-based compounds, such as zebra-shells. Overall, five-year-olds
      outperformed three-year-olds but performed significantly less well than adults.
      However, even at age 3, children did not show a general expectation to interpret
      the compounds literally.

PMID- 9154014
TI  - Lexically-based learning and early grammatical development.
AB  - Pine & Lieven (1993) suggest that a lexically-based positional analysis can
      account for the structure of a considerable proportion of children's early
      multiword corpora. The present study tests this claim on a second, larger sample
      of eleven children aged between 1;0 and 3;0 from a different social background,
      and extends the analysis to later in development. Results indicate that the
      positional analysis can account for a mean of 60% of all the children's multiword
      utterances and that the great majority of all other utterances are defined as
      frozen by the analysis. Alternative explanations of the data based on
      hypothesizing underlying syntactic or semantic relations are investigated through
      analyses of pronoun case marking and of verbs with prototypical agent-patient
      roles. Neither supports the view that the children's utterances are being
      produced on the basis of general underlying rules and categories. The
      implications of widespread distributional learning in early language development
      are discussed.

PMID- 9154015
TI  - Narrative discourse in Grammatical specific language impaired children: a modular
      language deficit?
AB  - This paper provides a further investigation into the linguistic abilities of a
      subgroup of 12 Grammatical specific language impaired (SLI) children (aged 10;2
      to 13;11). The study investigates the use of referential expressions (e.g.
      pronouns) in a narrative discourse, and provides insight into the underlying
      nature of Grammatical SLI, thereby contributing to the modularity debate.
      Previous investigations indicate that Grammatical SLI children have a deficit
      with dependent structural relationships, i.e. a Representational Deficit for
      Dependent Relationships (RDDR). Grammatical SLI children's RDDR appears to be a
      modular language deficit. To test this claim, linguistic representations of
      dependent structural relationships which are not part of the modular language
      system are investigated using a narrative discourse based on the picture book
      Frog where are you? The SLI children's pattern of referential expressions was
      compared with 36 language ability controls (aged 6;4 to 9;8). The findings
      indicated that the Grammatical SLI children have relatively mature linguistic
      development in the use of referential expressions to produce a cohesive,
      structured narrative discourse. The view of the organisation of the mind in which
      a modular language system can be differentially impaired from aspects of language
      which rely on the central system can most easily account for the data. Thus, the
      data support the hypothesized modular nature of Grammatical SLI children's
      underlying linguistic deficit. The implications of the findings for language
      acquisition are discussed.

PMID- 9154016
TI  - Conversational patterns of two-year-old twins in mother-twin-twin triads.
AB  - This study investigated the general nature of conversational interaction in
      mother-twin-twin triads. Four sets of firstborn twins (2;3) were videotaped
      during 15 minutes of free play with their mothers. Analyses revealed that triadic
      conversations were approximately five times longer, and elicited more turns from
      all speakers, than dyadic conversations between mother and a single twin. Twins
      also responded as often to comments and requests made to another person as to
      those directed to themselves, but responded more often to questions directly to
      them than to others, indicating reliable monitoring of language not addressed to
      them. These results largely parallel those reported for mother-infant-sibling
      triads and indicate the unique effects of triadic exchanges are not due to the
      relative linguistic levels of the child partners.

PMID- 9154017
TI  - Modern treatments for internal haemorrhoids.

PMID- 9154018
TI  - The future of locality commissioning.

PMID- 9154019
TI  - Is one arterial graft enough?

PMID- 9154020
TI  - The private finance initiative.

PMID- 9154021
TI  - Drug treatment for benign prostatic hyperplasia.

PMID- 9154022
TI  - Tobacco companies seek to pay $300bn as lawsuit settlement.

PMID- 9154023
TI  - The BMJs question time.

PMID- 9154024
TI  - Prospective cohort study of predictors of incident low back pain in nurses.
AB  - OBJECTIVE: To assess the impact of handling patients and indicators of individual
      susceptibility on risk of low back pain in nurses. DESIGN: Prospective cohort
      study with follow up by repeated self administered every three months over two
      years. SETTING: NHS university hospital trust. SUBJECTS: 961 female nurses who
      had been free from low back pain for at least one month at the time of completing
      a baseline questionnaire. MAIN OUTCOME MEASURES: Incidence of new low back pain
      during follow up and of pain leading to absence from work. RESULTS: Of 838 women
      who provided data suitable for analysis, 322 (38%) developed low back pain during
      follow up (mean 18.6 months), including 93 (11%) whose pain led to absence from
      work. The strongest predictor of new low back pain was earlier history of the
      symptom, and risk was particularly high if previous pain had lasted for over a
      month in total and had occurred within the 12 months before entry to the study
      (incidence during follow up 66%). Frequent low mood at baseline was strongly
      associated with subsequent absence from work for back pain (odds ratio 3.4; 95%
      confidence interval 1.4 to 8.2). After adjustment for earlier history of back
      pain and other potential confounders, risk was higher in nurses who reported
      frequent manual transfer of patients between bed and chair, manual repositioning
      of patients on the bed, and lifting patients in or out of the bath with a hoist.
      CONCLUSIONS: Of the indicators of individual susceptibility that were examined,
      only history of back trouble was sufficiently predictive to justify selective
      exclusion of some applicants for nursing posts. The main route to prevention of
      back disorders among nurses is likely to lie in improved ergonomics.

PMID- 9154025
TI  - Association of mutations in mannose binding protein gene with childhood infection
      in consecutive hospital series.
AB  - OBJECTIVE: To determine the extent to which mutations in the mannose binding
      protein gene predispose to childhood infection. DESIGN: Clinical details and
      genotype of mannose binding protein determined in consecutive children attending
      a paediatric department. SETTING: Inner city hospital paediatric service in
      London. SUBJECTS: 617 children attending hospital between October 1993 and August
      1995. MAIN OUTCOME MEASURE: Infection as the cause for attendance or admission in
      relation to mutations in the mannose binding protein gene. RESULTS: The
      prevalence of mutations in the mannose binding protein gene in children with
      infection (146/345) was about twice that in children without infection (64/272)
      (P < 0.0001). Increased susceptibility to infection was found in both
      heterozygotic and homozygotic children. 13 out of 17 children homozygotic for
      variant alleles presented with strikingly severe infections, including 6 with
      septicaemia. CONCLUSIONS: The findings suggest that mutations in the mannose
      binding protein gene are an important risk factor for infections in children.
      Screening for such mutations should be included in the investigation of severe or
      frequent infections.

PMID- 9154026
TI  - Is the clinical course of HIV-1 changing? Cohort study.
AB  - OBJECTIVE: To assess whether the clinical course of HIV infection has changed
      from 1985 to 1995. DESIGN: Cohort Study. SETTING: Infectious disease clinic.
      SUBJECTS: 285 patients recruited from September 1985 to January 1995 with < or =
      12 months between the dates of their last seronegative and first seropositive
      test result and with first follow up visit in the six months after seroconversion
      and at least 12 months' follow up. Patients were grouped according to the date of
      seroconversion. MAIN OUTCOME MEASURES: Time to CD4 cell count of < 500, 400, and
      200 x 10(6) cells/l, and clinical outcome defining AIDS; variation in cell count
      per day between consecutive visits, and ratio between this variation and time
      from estimated date of seroconversion at each visit. RESULTS: The groups were
      similar in age, number with acute primary HIV infection, CD4 cell count at
      intake, and cell count at the beginning of antiretroviral treatment; they
      differed in sex ratio, risk factors for HIV, probability of CD4 cell decline to <
      500, 400, and 200 x 10(6) cells/l. and risk of developing AIDS. Acute infection,
      seroconversion after December 1989, and serum beta 2 microglobulin > 296 nmol/l
      were independent predictors of poor clinical course. The speed of CD4 cell
      decline, expressed as cell variation divided by the number of days between
      consecutive visits, increased with more recent seroconversion (P = 0.02). Ratio
      between the speed of CD4 cell decline and time from estimated date of
      seroconversion at each visit was also higher in the patients who seroconverted
      after December 1989. CONCLUSIONS: The faster disease progression and the higher
      speed of CD4 cell decline at early stages in the patients with recently acquired
      HIV infection suggest changes in the clinical course of HIV infection.

PMID- 9154027
TI  - Meta-analysis of prophylactic or empirical antifungal treatment versus placebo or
      no treatment in patients with cancer complicated by neutropenia.
AB  - OBJECTIVE: To determine whether antifungal agents given prophylactically or
      empirically decrease morbidity and mortality in patients with cancer complicated
      by neutropenia. DESIGN: Meta-analysis of randomised trials of amphotericin B,
      various lipid soluble formulations of amphotericin B (for example, AmBisome),
      fluconazole, ketoconazole, miconazole, or itraconazole compared with placebo or
      no treatment. SETTING: Trials conducted anywhere in the world. SUBJECTS: Patients
      with cancer complicated by neutropenia. MAIN OUTCOME MEASURES: Mortality,
      invasive fungal infection (defined as positive blood culture, oesophageal
      candidiasis, or lung or deep tissue infection), and colonisation. RESULTS: 24
      trials with 2758 randomised patients were reviewed; the total number of deaths
      was 434. Prophylactic or empirical treatment with antifungals as a group bad no
      effect on mortality (odds ratio 0.92; 95% confidence interval 0.74 to 1.14).
      Amphotericin B decreased mortality significantly (0.58; 0.37 to 0.93) but the
      studies were small and the difference in number of deaths was only 15. Antifungal
      treatment decreased the incidence of invasive fungal infection (0.47; 0.35 to
      0.64) and fungal colonisation (0.45; 0.30 to 0.69). For every 73 patients treated
      (95% confidence interval to 48 to 158) one case of fungal invasion was prevented
      in surviving patients. CONCLUSIONS: There seems to be no survival benefit of
      antifungal agents given prophylactically or empirically to patients with cancer
      complicated by neutropenia. These agents should be restricted to patients with
      proved infection and those in randomised trials. A large, definitive placebo
      controlled trial of amphotericin B is needed.

PMID- 9154028
TI  - Impact of a dedicated service for male mentally disordered remand prisoners in
      north west London: retrospective study.

PMID- 9154029
TI  - What does locality commissioning in Avon offer? Retrospective descriptive
      evaluation.
AB  - OBJECTIVE: To describe the impact, direct costs of, and participants' attitudes
      to the first two years and eight months of locality commissioning in Avon.
      DESIGN: Retrospective description of programme. SETTING: Thirteen localities in
      Avon Health Authority area, covering 982000 population and 147 general practices.
      METHODS: Postal questionnaire survey of 147 general practitioners (one per
      practice); interviews with and questionnaire survey of 13 lead general
      practitioners and 13 so called link staff from the health authority. MAIN OUTCOME
      MEASURES: Locality initiatives, perceived influence, general practitioners'
      attitudes, management costs. RESULTS: Twenty initiatives were identified that had
      changed services to patients, and another nine were planned. The commonest
      initiatives concerned primary mental health care (seven), nurse specialists for
      primary care of chronic diseases (three), referral and clinical practice
      guidelines (seven), and access to hospital outpatient departments (one, with two
      others planned). Localities were more likely to have influenced the authority,
      trust managers, and consultants than social services, community health councils,
      and voluntary organisations. Activity varied between localities, lead general
      practitioners estimating that 120/147 (82%) of practices had been involved in
      locality meetings (range 44-100% in different localities). The authority had
      spent 6 p per capita on running the scheme, and the total time used by general
      practitioners for locality commissioning was estimated at 1.5 whole time
      equivalents. CONCLUSION: Locality commissioning has selectively changes services
      with limited extra funding and without delegation of hospital and community
      health service budgets. General practitioners wanted more policy and financial
      support. Further development should be based on evidence of costs, benefits, and
      limitations of locality commissioning schemes.

PMID- 9154030
TI  - Are the Health of the Nation's targets attainable? Postal survey of general
      practitioner's views.

PMID- 9154031
TI  - Evaluation of a decision support system for initiation and control of oral
      anticoagulation in a randomised trial.
AB  - OBJECTIVE: To determine whether a computerised decision support system for
      initiation and control of oral anticoagulant treatment improves quality of
      anticoagulant control achieved by trainee doctors. DESIGN: Randomised controlled
      trial. SETTING: District general hospital in North London. SUBJECTS: 148
      inpatients requiring start of warfarin treatment. INTERVENTIONS: Management by
      trainee doctors (to achieve therapeutic range of international normalised ratio
      of 2 to 3) with indirect assistance from computerised decision support system
      (intervention group) or without such assistance (control group). MAIN OUTCOME
      MEASURES: Median time to therapeutic range, stable dose, and first pseudoevent
      (excessive international normalised ratio after therapeutic range has been
      reached) and person time spent in the therapeutic range. RESULTS: 72 patients
      were randomised to the intervention group and 76 to control group. Median time to
      reach international normalised ratio of > or = 2 was not significantly different
      in the two groups (3 days). Median time to achieve a stable dose was
      significantly lower in intervention group than in controls (7 days v 9 days, P =
      0.01) without excessive overtreatment or undertreatment with anticoagulant.
      Patients in intervention group spent greater proportion of time in therapeutic
      range, both as inpatients (59% v 52%) and outpatients (64% v 51%). CONCLUSION:
      The computerised decision support system was safe and effective and improved the
      quality of initiation and control of warfarin treatment by trainee doctors.

PMID- 9154032
TI  - Science, medicine, and the future. Hypertension.
AB  - The abundance of drugs now available for treating hypertension, and evidence that
      small reductions in blood pressure reverse the associated risk of stroke have
      shifted clinical concerns away from hypertension. However, we do not understand
      the cause of hypertension in 95% of patients, fail to achieve a normal blood
      pressure in 50% of patients, and are unable fully to reverse the cardiac and
      vascular changes that predate the diagnosis and treatment of hypertension.
      Consequently, hypertension remains the commonest cause of strokes in Britain and
      of renal failure in the United States. Essential hypertension is a polygenic
      disease whose understanding can now be advanced through molecular genetic
      analyses. Several different syndromes are likely to be recognised; most will be
      due to interactions between genetic and environmental factors, but there are also
      likely to be further monogenic syndromes in families with multiple affected
      members. Recognition of these syndromes will permit accurate genetic prediction
      of prognosis and optimal treatment and perhaps lead to new and more powerful
      classes of antihypertensive treatment.

PMID- 9154033
TI  - ABC of clinical haematology. Haematological disorders at the extremes of life.

PMID- 9154034
TI  - What happens when the private sector plans hospital services for the NHS: three
      case studies under the private finance initiative. NHS Consultants' Association,
      Radical Statics Health Group, and the NHS Support Federation.

PMID- 9154036
TI  - Bureaucracy of purchaser-provider split delays treatment.

PMID- 9154035
TI  - Life expectancy, economic inequality, homicide, and reproductive timing in
      Chicago neighbourhoods.
AB  - In comparisons among Chicago neighbourhoods, homicide rates in 1988-93 varied
      more than 100-fold, while male life expectancy at birth ranged from 54 to 77
      years, even with effects of homicide mortality removed. This "cause deleted" life
      expectancy was highly correlated with homicide rates; a measure of economic
      inequality added significant additional prediction, whereas median household
      income did not. Deaths from internal causes (diseases) show similar age patterns,
      despite different absolute levels, in the best and worst neighbourhoods, whereas
      deaths from external causes (homicide, accident, suicide) do not. As life
      expectancy declines across neighbourhoods, women reproduce earlier; by age 30,
      however, neighbourhood no longer affects age specific fertility. These results
      support the hypothesis that life expectancy itself may be a psychologically
      salient determinant of risk taking and the timing of life transitions.

PMID- 9154037
TI  - Counting the cost of social disadvantage in primary care. Conclusions arising
      from economic evaluations in primary care should be treated with caution.

PMID- 9154038
TI  - Counting the cost of social disadvantage in primary care. Authors excluded people
      who should have been included.

PMID- 9154039
TI  - Community mental health teams in London are being increasingly stretched.

PMID- 9154040
TI  - Cervical screening. Rate of diagnosis of cytological abnormalities is best end
      point.

PMID- 9154041
TI  - Cervical screening. Large mismatch exists between cancers and surrogate end
      points.

PMID- 9154042
TI  - Cervical screening. Effect of screening may be being underestimated.

PMID- 9154043
TI  - Home medical students account for less than half the full registrants Britain
      requires.

PMID- 9154044
TI  - Recommendations for improving national data on congenital anomalies are being
      implemented.

PMID- 9154045
TI  - Crisis in London's mental health services. Empirical evidence was lacking in
      study.

PMID- 9154046
TI  - Crisis in London's mental health services. Meeting the needs of people with
      learning disabilities would unblock acute beds.

PMID- 9154047
TI  - Crisis in London's mental health services. Providing cash is not the only answer
      for ailing mental health services.

PMID- 9154048
TI  - Crisis in London's mental health services. Do we need more psychiatric beds?

PMID- 9154049
TI  - Crisis in London's mental health services. Stop gap remedies.

PMID- 9154050
TI  - Bodybuilders find it easy to obtain insulin to help them in training.

PMID- 9154051
TI  - Dangers of sunbeds are greater in the commercial sector.

PMID- 9154052
TI  - Junior surgeons are becoming deskilled as result of Calman proposals.

PMID- 9154053
TI  - New government must reassess its criminal justice policy.

PMID- 9154054
TI  - Prophylaxis of venous thromboembolism. Article did not give enough information.

PMID- 9154055
TI  - Prophylaxis of venous thromboembolism. Regional anaesthesia reduces
      thromboembolic morbidity.

PMID- 9154056
TI  - Not all those who died after Hillsborough did so by 3 15 pm.

PMID- 9154057
TI  - Concussive convulsions. Editorial perpetuated myths about convulsive syncope.

PMID- 9154058
TI  - Concussive convulsions. Wrong diagnosis may deprive people of their livelihood.

PMID- 9154059
TI  - Chemoprevention of colorectal cancer.

PMID- 9154060
TI  - Colorectal cancer epidemiology in Italy and screening perspectives.

PMID- 9154061
TI  - Prognostic factors in human colorectal cancer.

PMID- 9154062
TI  - Follow-up in colorectal cancer.

PMID- 9154063
TI  - Colorectal cancer: biological aspects prognosis related and follow-up.

PMID- 9154064
TI  - Hepatic metastases from colorectal cancer.

PMID- 9154065
TI  - Lung metastasectomy for colorectal cancer.

PMID- 9154066
TI  - Update on adjuvant therapy of colon cancer.

PMID- 9154067
TI  - Adjuvant treatment of colorectal cancer. The European experience.

PMID- 9154069
TI  - Protracted infusional 5-fluorouracil for colorectal cancer.

PMID- 9154068
TI  - Adjuvant chemotherapy for colon cancer: Italian studies.

PMID- 9154070
TI  - The value of weekly high dose infusional 5-fluorouracil in the treatment of
      advanced colorectal cancer.

PMID- 9154071
TI  - Hepatic arterial infusion (HAI) for unresectable liver metastases (ULM) from
      colorectal carcinoma.

PMID- 9154073
TI  - Therapies for advanced colorectal cancer: the role of interferon and leucovorin.

PMID- 9154072
TI  - Inhibition of thymidylate synthase: biochemical pharmacology of drugs with
      activity in colorectal cancer.

PMID- 9154074
TI  - Efficacy and tolerability of a new inhibitor of thymidylate synthase: 'Tomudex'
      (raltitrexed).

PMID- 9154075
TI  - Results of a European multicentre trial of Tomudex versus 5-FU/high dose LV
      (Machover regimen).

PMID- 9154076
TI  - Response evaluation as the key-point in results interpretation.

PMID- 9154077
TI  - Beyond the clinic: future challenges for therapy.

PMID- 9154078
TI  - CPT-11 (irinotecan) in the treatment of colorectal cancer: a new mechanism of
      action for additional activity.

PMID- 9154079
TI  - Doxifluridine: previous experience and new developments in the treatment of
      colorectal cancer.

PMID- 9154080
TI  - 5-Fluorouracil prodrug, ftorafur, modulated by uracil (UFT): preclinical and
      clinical prospective.

PMID- 9154081
TI  - The development of radiotherapy: physics, technology methods.
AB  - Radiotherapy was introduced in Sweden already before the turn of the century, ie,
      a few years after the discovery of x-rays and radioactivity. Pioneering
      contributions were made by Forssell, Berven, Heyman, Sievert, and Strandqvist in
      general radiotherapy, gynecologic radiotherapy, dosimetry, teleradium methods,
      and radiation biology. Technological advancements, along with nearly 100%
      followup of treatment effects, created a foundation for compiling early empirical
      experience in a methodologically sound specialty. Therapeutic radiology in Sweden
      was distinguished from diagnostic radiology already in 1917, at which time the
      specialties of general and gynecologic radiotherapy were founded. These
      specialties later developed into general and gynecologic oncology. Progress
      during recent decades has been characterized by access to better equipment such
      as telegamma devices and accelerators for external radiotherapy, and new
      radionuclides, eg, for remote controlled local application. With CT (computed
      tomography) and MRI (magnetic resonance imaging), SPECT and PET (tomography using
      gamma radiation and positron-irradiated nuclides), and ultrasound diagnostics,
      the anatomic basis for individual dose planning has radically improved. Dosage
      can now be planned with high precision and visualized in three dimensions using
      advanced computer programs. Technical safety has increased with improved methods
      for in vivo dosimetry and computer-controlled verification of all parameters for
      every treatment. It is now possible to deliver the intended radiation dose to a
      benign tumor without causing serious side effects. Important research fields
      include the impact of different fractionation schedules on the effects of
      radiation and how radiotherapy can best be combined with other forms of therapy
      such as surgery and chemotherapy.

PMID- 9154082
TI  - What is radiotherapy?

PMID- 9154083
TI  - Organization of radiotherapy and cancer care in Sweden.

PMID- 9154084
TI  - Cancer trends in Sweden until 2010.
AB  - To arrive at a reasonable estimate of the total need for radiotherapy, the
      various descriptions of population trends and measures of cancer trends must be
      studied concurrently. Incidence and mortality are well documented by official
      statistics. All prognoses are based on these measures, the official population
      statistics, and the 1989 population prognosis from Statistics Sweden. Incidence,
      mortality, and prevalence may be considered either individually or together as
      indirect measures of the need for radiotherapy at different stages for different
      types of cancer. Incidence, ie, the number of cases of disease onset during a
      given period, shows the indirect need for curative radiotherapy, eg, for breast
      cancer, laryngeal cancer, gynecological tumor types, and head and neck cancer.
      The projected average annual mean increase in total incidence is 1.0%. Mortality
      may be used as an indirect measure of the need for palliative treatment for
      recurring cancer, eg, for bone metastases, prostate cancer, lung cancer, or
      breast cancer. The mean increase is estimated at 0.9% per year. Likewise,
      prevalence can be an indirect measure of the need for palliative treatment for
      cancer diseases of a chronic nature, eg, prostate cancer and multiple myeloma.
      The total mean increase per year has been estimated at 2.0%. The total need for
      radiotherapy in the future should be viewed against the background of all these
      descriptive measures. Assessment must also consider numerous other factors that
      directly influence need. A change in the indications for treatment can quickly
      increase the need for radiotherapy, eg, the benefits of radiotherapy for
      noninvasive breast cancer are currently being studied. Even a change in the
      indications for surgical intervention for small tumors in the breast influence
      the need for primary curative radiotherapy in this large group of patients.
      Likewise, a shift in staging the primary diagnosis, eg, in head and neck cancer,
      and changes in fractionation (hyperfractionation) may substantially influence
      need. This is addressed further in another section of the report. The largest
      single group of cancer patients who receive radiotherapy are those with bone
      metastases (25% of the total). The size of this group, and thereby the potential
      unsatisfied need, is largely unknown since no statistics show the prevalence of
      metastases in the population. This group is comprised mainly of patients that
      were primarily diagnosed with prostate cancer, breast cancer, and lung cancer.
      Concerning lung cancer, incidence trends probably provide the best measure of
      changes in the number of bone metastases over time. The annual increase in
      incidence has been estimated at 1.5%. As for breast cancer and prostate cancer,
      mortality trends provide more information about trends in the number of bone
      metastases. Both types of cancer increased by 1.9% per year. Chapter 6 presents
      the types of cancer for which radiotherapy is usually given. The projected trends
      show that each of these cancer diagnoses, except lung cancer in men and cervical
      cancer in women, are expected to increase in number until the year 2010.
      Prevalence is expected to increase even more, particularly cancer in the rectum,
      breast, and prostate. Also, the number of cases of non-Hodgkin's lymphoma is
      expected to nearly double by 2010.

PMID- 9154085
TI  - A prospective survey of radiotherapy in Sweden.
AB  - A prospective survey was conducted of patients who began radiotherapy in Sweden
      during 12 weeks in the autumn of 1992. All hospitals that provided radiotherapy
      participated. The goal was to study the most common diagnoses, corresponding to
      approximately 80% of the patients. A special analysis involving all patients who
      started radiotherapy in 1992 at Sweden's largest unit, Radiumhemmet in Stockholm,
      revealed that the goal had been achieved. Overall, the assessment showed the data
      to be representative and of good quality. The analysis included 2988 patients, of
      whom 2776 received external radiotherapy alone, 63 received both external
      radiotherapy and brachytherapy, and the remaining 149 received brachytherapy
      alone. As expected, the two most common diagnoses were breast cancer and prostate
      cancer. To evaluate the total number of patients receiving radiotherapy in Sweden
      in 1992, the results of the study were related to the results of the economic
      assessment from 1991 described in Chapter 8. The assessment shows that
      approximately 13000 patients began radiotherapy in Sweden in 1992, ie, almost one
      third of cancer patients receive radiotherapy at some time during the course of
      their disease. The mean age of radiotherapy patients was 64 years, and 55% of all
      patients were women. Half of the patients received curative treatment, and the
      other half palliative treatment. The proportion of curative treatments varied
      considerably among the departments, from 23% to 86%. The proportion was 39% at
      county departments, compared to 52% at regional departments, and 76% at the
      gynecologic oncology departments. Palliative treatment was usually provided by
      less complicated methods, using fewer fractions and fewer fields. The proportion
      of curative fractions was 68%, and the proportion of curative fields was 72%. The
      proportion of curative treatments also varied greatly among different diagnostic
      groups, from 82% for head and neck cancer to 17% for lung and prostate cancer. Of
      patients receiving primary treatment, one third received radiotherapy alone and
      the remainder received a combination of radiotherapy and other treatment, usually
      surgery. Thirty-three percent of the patients were treated in accordance with
      clinical protocols or studies, with a somewhat higher proportion of these
      patients at the gynecologic oncology departments. The figures varied between 82%
      for gastrointestinal cancer and 11% for prostate cancer. Curative treatment was
      delivered, on average, using 23 fractions, 2.6 fields, and 49 Gy. The highest
      dosage, most fractions, and most fields were delivered for prostate cancer and
      head and neck cancer. The lowest doses were given for malignant lymphoma.
      Corresponding figures for palliative treatment were 11 fractions, 2.0 fields and
      30 Gy. Of patients receiving palliative therapy, 60% were treated for bone
      metastases. These patients were treated with 8 fractions, 1.7 fields, and 27 Gy.
      With regard to curative and palliative treatment alike, there was a tendency for
      regional departments to give more fractions and higher doses than the county
      departments. No differences in sex or age appeared regarding the number of
      fractions, the number of fields, and the dose, except in patients over age 85
      years where lower figures reflected a higher proportion of palliative treatments.
      With one exception only, patients with gynecologic cancer were the ones who
      received brachytherapy. Seventy percent of the patients had cancer in the body of
      the uterus. They received an average of four treatments, three for those who also
      received external radiotherapy. The number of brachytherapy treatments varied
      widely by department. This can be explained by two different therapeutic
      traditions: one tradition uses agents with low radiation intensity per time unit,
      resulting in fewer and longer treatments, and the second tradition involves
      agents with high radiation intensity per time unit, resulting in more, although
      shorter, treatments.

PMID- 9154086
TI  - Cost of radiotherapy in Sweden.
AB  - This chapter addresses the economic aspects of radiotherapy. It includes a
      summary of the costs for radiotherapy in Sweden, a literature review of economic
      studies on cancer radiotherapy, and estimates of radiotherapy costs in Sweden for
      1991. Appendix I describes the types of economic assessments relevant to an
      economic analysis of radiotherapy. Appendix II analyzes potential economies of
      scale, and the economic consequences of changed fractionation schedules. Cancer
      diagnosis and treatment accounts for approximately 5% of the total healthcare
      expenditure in Sweden (1), corresponding to 6.9 billion Swedish kronor (SEK) per
      year in 1993 monetary value. The costs of radiotherapy, an important modality for
      treating cancer, have not been fully described. This report presents such an
      estimate. The cost of external radiotherapy in Sweden in 1991 was approximately
      260 million SEK. This corresponds to approximately 4% of the cost for cancer
      care. On average, the cost per irradiated field was approximately 500 SEK, the
      cost per fraction approximately 1125 SEK, and the cost per patient approximately
      17,200 SEK. The estimates per patient vary widely by group. A rough estimate of
      the cost for curative radiotherapy for breast cancer would be approximately
      31,000 SEK, which can be contrasted with a cost of approximately 7000 SEK for
      palliative treatment of bone metastases. The cost for brachytherapy in 1991 was,
      according to departmental financial reports, approximately 36 million SEK. Hence,
      the costs for external radiotherapy and brachytherapy were approximately 300
      million SEK in 1991. In 1993 prices, this corresponds to approximately 330
      million SEK, representing the total direct costs for radiotherapy in Sweden.
      However, this figure does not include costs for, eg, hospitalization in
      conjunction with radiotherapy, nor the other costs associated with this type of
      treatment. Several potential sources of error underlie these figures. The
      following overview presents and evaluates the foundation for these estimates.
      Appendix I to this chapter discusses the problem of how these estimates should be
      defined, and how costs should be related to the different ways for measuring
      treatment results.

PMID- 9154087
TI  - Quality assurance and radiotherapy.
AB  - As mentioned in several chapters of this report, administering the radioactive
      dosage requires a high level of precision. Demands on precision dosimetry have
      increased with modern curative radiotherapy. A few percent increase or decrease
      in the dose level may, in some cases, represent the difference between successful
      and unsuccessful therapy (Chapter 10). High precision is therefore required of
      basic dosimetry for different types and qualities of radiation, and in applied
      dosimetry for, eg, dose planning and in vivo dosimetry. External audits should be
      used to avoid systemic error. Comparative dose measurements are important, both
      to establish variations within a department and between departments. Simulators
      and/or therapeutic equipment should be checked regularly to assure that the
      direction of the radioactive beam and the field size complies with the plan.
      Margins that are too narrow can miss part of the target volume and increase the
      risk for relapse. If, on the other hand, the margins are too wide, the reaction
      to radiation in nearby organs at risk may be unacceptable. Accessible field
      control images should therefore be integrated in regular routines, at least when
      the margins between tumors and risk organs are small.

PMID- 9154088
TI  - Future developments in radiotherapy.
AB  - Radiotherapy has advanced rapidly during the past two decades, mainly through
      developments in high-voltage equipment and diagnostic methods that can better
      define tumor boundaries. Methods to improve the application of these developments
      are constantly being refined. Knowledge is increasing about treatment plans for
      different types of tumors, mainly concerning dosage and fractionation. Continued
      optimization efforts and quality improvements should be able to increase the 5
      year survival rate among radiotherapy patients in Sweden, just with the
      application of current knowledge. Based on extrapolations from estimates
      concerning potential improvements in radiotherapy methods, it is estimated that
      an additional 10% of radiotherapy patients could be cured during the next 10
      years. Since approximately 30% of all cancer patients in Sweden receive
      radiotherapy with curative intent, an additional 3% of the total cancer
      population could be treated with curative results. Naturally, these estimates
      involve some uncertainty. For example, a report from EU (1) estimated that an
      improvement in the quality of radiotherapy in Western Europe should improve
      survival for 5% of the cancer patients, a somewhat higher value than has been
      estimated for Sweden. Trials are under way to use radiosensitizing substances and
      new laboratory tests to further define the radiosensitivity of tumors. The result
      may be improved, individually-oriented radiotherapy. The combination of
      radiotherapy and chemotherapy has mostly shown discouraging results thus far. The
      combination of radiotherapy and surgery is used often and further developments
      can be expected. The extent to which these new developments improve therapy is,
      however, difficult to project.

PMID- 9154089
TI  - Future developments in treatment methods other than radiotherapy.
AB  - Increasingly more cancer patients are being diagnosed at an early stage in the
      disease. Consequently, more patients receive curative treatment. Milder methods
      and better care even make curative treatment an alternative for medically frail
      patients. As knowledge advances, primary curative treatment is becoming more
      complicated and embraces more forms of treatment. The local treatment methods,
      surgery and radiotherapy, will continue to play at least as large, or perhaps a
      larger, role in the outcome of cancer. Even for patients who cannot be cured,
      meaningful treatment is successively improving and resulting in longer and better
      lives for patients. This, coupled with the expected increase in the number of
      cancer patients discussed in Chapter 5, will result in an increasing and rapid
      overall need for cancer treatment. Surgery is expected to continue developing
      toward becoming increasingly mild and organ-conserving. Endoscopic methods will
      continue to expand. Chemotherapy will advance further, mainly through increased
      knowledge about active mechanisms and possibilities of combination therapy. This
      will lead to a successive, gradual improvement in results, and chemotherapy will
      become a meaningful approach for treating more cancers. Bone marrow
      transplantation, both allogeneic and autologous, and stem cell transplantation,
      is expected to continue. Hormonal treatment will continue. Through the
      introduction of new agents and applications for more diagnoses, the use of this
      method may expand, perhaps mainly in adjuvant situations. Biologic therapy is at
      an early stage in development. It has become an established treatment approach
      for certain types of cancer. Continued, intensive research can be expected. The
      practical potential for improving treatment results is, however, expected to be
      somewhat limited in the foreseeable future. With most cancers, primary treatment
      has the potential to cure the patient, but cure becomes less attainable on
      relapse. The greatest progress in recent decades has not involved curing more
      patients, but improving the care of those who cannot be cured. This trend will
      continue, which will place greater demands mainly on nursing care and palliative
      treatment. Nothing suggests that the development of other treatment methods will
      reduce the need for radiotherapy. However, much suggests that local treatment
      methods will gain increased importance, particularly if the trend continues
      toward early detection of more cancers.

PMID- 9154091
TI  - Radiotherapy for cancer. Volume 2: a critical review of the literature.
      Introduction.

PMID- 9154090
TI  - Radiotherapy practices in Sweden compared to the scientific evidence.
AB  - Comparing the scientific literature to practices in Sweden reveals that
      radiotherapy is given to less than 34% of all patients with tumor diseases. This
      figure is lower than rates reported in other countries. For most tumor types,
      curative radiotherapy in Sweden is generally similar to practices supported in
      the literature. Hyperfractionated radiotherapy and interstitial brachytherapy are
      used much too sparingly. Palliative radiotherapy is underutilized in Sweden. The
      need for radiotherapy can be expected to increase until the year 2010.

PMID- 9154092
TI  - Brain tumors.
AB  - This synthesis of the literature on radiotherapy for brain tumors, ie, cancer
      originating in the central nervous system (CNS), is based on 81 scientific
      articles, including 25 randomized studies, 13 prospective studies, and 25
      retrospective studies. These studies involve 11,081 patients. A more
      comprehensive chapter on brain tumors may be ordered from SBU. Curative treatment
      is not available for patients with highly malignant glioma (grades III and IV).
      Postoperative radiotherapy for highly malignant glioma extends patients'
      survival, with good quality of life, by several weeks to several months.
      Virtually all patients die from this disease. Although the clinical benefits from
      radiotherapy, measured as survival, appear to be modest, it is more effective
      than any chemotherapy tested thus far. The clinical effects of radiotherapy for
      highly malignant glioma are improved only marginally by altering factors such as
      absorbed dose, fractionation, irradiated tissue volume, radiation quality, or by
      adding radiosensitizing substances. Radiotherapy alone usually provides a clear
      but temporary improvement in patients with highly malignant glioma, hence it
      clearly has a palliative benefit. Postoperative radiotherapy for low-grade
      malignant gliomas (grades I and II) may extend survival. It also reduces tumor
      volume. No evidence shows that radiotherapy alone or postoperatively can lead to
      cure. In patients who have undergone subtotal meningioma resection, postoperative
      radiotherapy substantially reduces the risk for recurrence and extends life, and
      is thereby indicated. Radiotherapy is not indicated following macroscopic radical
      meningioma surgery. Patients with brain metastases experience rapid neurological
      improvement following radiotherapy to the whole brain, and this palliative effect
      often remains throughout the remainder of the patient's life. Palliative
      radiotherapy, often to large volumes of the CNS, is therefore motivated in a
      large proportion of the patient groups. In a smaller group of patients with
      solitary metastases, radiotherapy may be given postoperatively following radical
      neurosurgery. Life may be extended in this group, otherwise radiotherapy does not
      influence survival. Stereotactic radiotherapy of solitary, mainly spherical
      metastases in the brain is often superior to other known methods with respect to
      palliation and survival. The number of patients is, however, relatively small.

PMID- 9154093
TI  - Head and neck cancer.
AB  - This synthesis of the literature on radiotherapy for head and neck cancer is
      based on 424 scientific articles, including 3 meta-analyses, 38 randomized
      studies, 45 prospective studies, and 246 retrospective studies. These studies
      involve 79174 patients. The literature review shows that radiotherapy, either
      alone or in combination with surgery, plays an essential role in treating head
      and neck cancers. When tumors are localized, many tumor patients can be cured by
      radiotherapy alone and thereby maintain full organ function (1, 2). Current
      technical advancements in radiotherapy offer the potential for better local tumor
      control with lower morbidity (3). This, however, will require more sophisticated
      dose planning resources. To further improve treatment results for advanced
      tumors, other fractionation schedules, mainly hyperfractionation, should be
      introduced (5). This mainly increases the demands on staff resources for
      radiotherapy. The combination of radiotherapy and chemotherapy should be
      subjected to further controlled studies involving a sufficiently large number of
      patients (4, 5). Interstitial treatment (in the hands of experienced
      radiotherapists) yields good results for selected cancers. The method should be
      more generally accessible in Sweden. Intraoperative radiotherapy should be
      targeted for further study and development.

PMID- 9154094
TI  - Lung cancer.
AB  - This synthesis of the literature on radiotherapy for lung cancer is based on 80
      scientific articles, including 2 meta-analyses, 29 randomized studies, 19
      prospective studies, and 21 retrospective studies. These studies involve 28172
      patients. Basic treatment for limited-stage small cell lung cancer (SCLC), is
      chemotherapy. Addition of radiotherapy to the primary tumor and mediastinum
      reduces local recurrence, prolongs long-term survival, and is often indicated.
      Current, and future, studies can be expected to show successive improvements in
      results for SCLC by optimizing the combination of radiotherapy and chemotherapy.
      Should these treatments be given simultaneously or sequentially, and in which
      order? Which fractionation is best? Probably, no change in resource requirements
      for radiotherapy will be necessary, with the possible exception of changes in
      fractionation. Surgery constitutes primary treatment for nonsmall cell lung
      cancer (NSCLC) stages I and II. Radiotherapy may provide an alternative for
      patients who are inoperable for medical reasons. The value of radiotherapy
      following radical surgery for NSCLC remains to be shown. It is not indicated
      based on current knowledge. For NSCLC stage III, radiotherapy shrinks tumors and
      prolongs survival at 2 and 3 years. Whether it influences long-term survival
      after 5 years has not been shown. Considering the side effects of treatment, one
      must question whether limited improvements in survival motivate routine
      radiotherapy in these patients. Earlier attempts to add chemotherapy to
      radiotherapy to improve treatment results of NSCLC have not yielded convincing
      results. Several studies are currently on-going. Prophylactic cranial irradiation
      (PCI) greatly reduces the risk for brain metastases from SCLC. However, it has
      little influence on survival. Many treatment centers give PCI to SCLC patients
      who have achieved complete remission. This practice may be questioned since PCI
      is associated with serious complications. PCI is not indicated in patients with
      NSCLC. In SCLC, where the disease is extensive, only palliative radiotherapy is
      appropriate. Radiotherapy is an important treatment alternative in special
      palliative situations involving severe cough, severe bleeding, pain, pulmonary
      obstructions, and vena cava superior syndrome. In these situations, good results
      may be achieved with few fractions.

PMID- 9154095
TI  - Breast cancer.
AB  - This synthesis of the literature on radiotherapy for breast cancer is based on 97
      scientific articles, including 5 meta-analyses, 38 randomized studies, and 27
      retrospective studies. These studies involve 387634 patients. Radiotherapy is the
      most effective method for preventing locoregional recurrence following primary
      surgery for invasive breast cancer, and radiotherapy is currently more effective
      than adjuvant chemotherapy after either mastectomy or breast-conserving surgery.
      Radiotherapy in patients at high risk for locoregional recurrence, eg, patients
      with spread to the axillary lymph nodes, leads to a significant increase in
      relapse free survival (eg, 1, 3). Meta-analyses have shown that radiotherapy in
      these subgroups of patients can reduce the risk for distant metastasis and reduce
      the risk for cancer death. These analyses have not statistically confirmed an
      improvement in total survival, probably because reduced mortality from breast
      cancer has been offset by increased mortality from cardiovascular disease.
      However, the results have successively improved, and survival gains are
      significantly greater in recent studies using modern treatment methods. It is
      probable that survival gains from radiotherapy do not exceed those that can be
      achieved by other adjuvant treatment of breast cancer such as chemotherapy or
      hormones, ie, a reduction in mortality by 20% to 30%, leading to an increased
      total survival after, eg, 10 years of 5% to 10%. The heart is the most important
      organ at risk during radiotherapy for breast cancer. Minimizing radiation doses
      to the heart muscle and the coronary arteries is necessary for avoiding later
      effects of ischemic cardiovascular disease. These side effects were particularly
      prominent in early treatment studies that used older radiotherapy methods.
      Radiotherapy in conjunction with breast-conserving surgery for invasive breast
      cancer significantly reduces the recurrence frequency in the breast. Clinical
      studies are under way that aim at further defining the role of radiotherapy as an
      element in a breast-conserving treatment strategy, e.g., determining the value of
      boost, and identifying prognostic/predictive factors for breast recurrence.
      Improved knowledge about such factors should eventually permit identification of
      patient groups at such low risk for breast recurrence that routine radiotherapy
      is unnecessary, or at such high risk-even with radiotherapy-that alternatives to
      breast conserving surgery should be considered. Radiotherapy also reduces the
      risk for recurrence in the breast following breast-conserving surgery of DCIS.
      Controlled trials are under way that aim at more closely defining the roles of
      surgical methods and radiotherapy for various subgroups of patients, eg,
      regarding different histopathologic types of DCIS. Radiotherapy has a substantial
      palliative value to patients who cannot be cured. It can reduce, prevent, or
      delay unpleasant symptoms from advanced disease, eg, pain, cancer lesions,
      fractures, neurologic symptoms. etc.

PMID- 9154096
TI  - Rectal cancer.
AB  - This synthesis of the literature on radiotherapy for rectal cancer is based on 73
      scientific articles, including 1 meta-analysis, 32 randomized studies, 22
      prospective studies, and 1 retrospective study. These studies involve 15042
      patients. The reviewed studies show that adjuvant radiotherapy for operable
      rectal cancer can reduce the risk for local recurrence. A meta-analysis of 11
      randomized studies reported a 25% risk reduction. The same meta-analysis suggests
      that adjuvant radiotherapy can reduce mortality by 10%, but this has not been
      statistically confirmed. The clinical effects of radiotherapy may depend on when
      it is given in relation to surgery. The issue of preoperative or postoperative
      radiotherapy is being investigated in several prospective randomized studies.
      Fractionation, administration of anticancer drugs during radiotherapy, and
      surgical methods, including associated radicality, also appear to be of
      importance. Local recurrence of rectal cancer is accompanied by severe suffering
      for the patient, eg, severe pain that is difficult to control by medication and
      surgery. Hence, there are major benefits from avoiding local recurrence. Given
      current knowledge, radiotherapy (preferably preoperative) is indicated in
      conjunction with operable rectal cancer, mainly Dukes' group C. External
      radiotherapy provides valuable palliation in many patients with locally advanced
      rectal cancer. In isolated cases, treatment appears to lead to prolonged disease
      free survival, mainly in patients with local recurrence who have not already
      received pre- or postoperative radiotherapy. Experiences from different models of
      combination therapy involving chemotherapy and intraoperative radiotherapy are
      too limited to permit reliable conclusions: mainly since observation times are
      relatively short.

PMID- 9154097
TI  - Prostate cancer.
AB  - This synthesis of the literature on radiotherapy for prostate cancer is based on
      53 scientific articles, including 4 randomized studies, 3 prospective studies,
      and 44 retrospective studies. These studies involve 52005 patients. The
      literature provides no apparent evidence to motivate radiotherapy, or any
      treatment, for highly differentiated T0 tumors. Some findings suggest that
      radiotherapy or surgery may be indicated for poorly differentiated tumors. The
      literature however shows no differences in tumor effects between these two
      methods for treating T0 tumors. Radiotherapy is milder and less mutilating.
      Conclusions cannot be drawn from the literature concerning whether surgery
      (radical prostatectomy) or external radiotherapy is preferable for T1 and T2
      tumors. Most probably, some patients are more suitable for surgery, others for
      radiotherapy. More patients are, nevertheless, candidates for radiotherapy. The
      value of external radiotherapy for T3 tumors is documented. Radiotherapy is
      valuable as palliative treatment for T4 tumors. Radiotherapy may be valuable as
      localized, symptom-relieving treatment for generalized prostate cancer. Treatment
      given via a few high fractions saves patients' time, hospitalization, and
      resources. Concerning individualized treatment, the differentiation grade is
      important for the choice of treatment method, mainly in early, but even in late
      clinical stages. This may involve choosing between radiotherapy and endocrine
      therapy, or even choosing between radiotherapy and surgery. The value of external
      radiotherapy increases as the differentiation grade of the tumor decreases. It is
      essential to treat patients at facilities that have the diagnostic potential to
      establish the differentiation grade of tumors. The value of postoperative
      radiotherapy has not yet been demonstrated at any clinical stage of prostate
      cancer. Treatment results from interstitial brachytherapy alone appear to be
      clearly inferior to the results from other methods. The value of combining
      interstitial/external radiotherapy should be studied further.

PMID- 9154098
TI  - Cervical cancer (cervix uteri).
AB  - This synthesis of the literature on radiotherapy for cervical cancer (cervix
      uteri) is based on 59 scientific articles, including 8 randomized studies, 1
      prospective study, and 36 retrospective studies. These studies involve 34,024
      patients. Due to favorable anatomy and exceptionally good radiation tolerance of
      nearby pelvic organs, particularly the uterus, radiotherapy has become the
      dominant treatment method for cervical cancer. Surgery alone is used at the
      earliest stages where small tumor volumes are involved. Further pathological
      findings, where cancer is more extensive than expected preoperatively, or when
      lymph node metastases are discovered, motivate postoperative radiotherapy even at
      early stages. There is general agreement that advanced cervical cancer should be
      treated by radiotherapy alone. Clinical trials are under way that combine
      radiotherapy and chemotherapy, and even surgery. Two different methods of
      intracavitary brachytherapy are currently in use, low-dose rate therapy and high
      dose rate therapy. High-dose rate therapy appears to be economically more
      favorable. The possibility of higher risks for later complications associated
      with high-dose rate therapy has not been fully studied.

PMID- 9154099
TI  - Uterine cancer (corpus uteri).
AB  - This synthesis of the literature on radiotherapy for cancer originating in the
      endometrium of the uterus (corpus uteri) is based on 55 scientific articles,
      including 2 randomized studies, 1 prospective study, and 48 retrospective
      studies. These studies involve 13597 patients. Endometrial cancer is a
      radiosensitive cancer. Research findings compiled for the period 1948 to 1954
      showed that 69% of the patients could be cured by radiotherapy alone. During the
      1970s it was shown that combined radiotherapy and surgery yielded better results.
      There is agreement that patients at stage I should receive primary surgery.
      According to the literature, there is controversy about whether patients with
      poorly differentiated tumors should be given preoperative radiotherapy.
      Radiotherapy alone can be used successfully in patients who are inoperable
      because of age, general condition, or advanced spread of cancer. Vaginal
      postoperative radiotherapy is used in most patients and reduces the percentage of
      patients who develop vaginal metastases from 7%-20% to less than 1%. Patients
      with good prognostic factors have such a low risk for metastasis that withholding
      radiotherapy may be considered in this group. Postoperative external radiotherapy
      improves survival in patients with unfavorable prognostic factors, such as deep
      myometrium invasion or signs of node metastasis. Radiotherapy is delivered, in
      principle, to all patients with poorly differentiated disease. It can be expected
      that most cases of endometrial cancer will continue to be referred for some form
      of radiotherapy.

PMID- 9154100
TI  - Ovarian cancer.
AB  - This synthesis of the literature on radiotherapy for cancer originating in the
      ovaries is based on 74 scientific articles, including 12 randomized studies, 18
      prospective studies, and 36 retrospective studies. These studies involve 6,140
      patients. Treatment for patients at early stages of ovarian cancer (stages I and
      II) is surgery. The value of adjuvant treatment, ie, chemotherapy or
      radiotherapy, is not demonstrated. Tumor volume is decisive to the success of
      radiotherapy. Microscopic or small macroscopic cancer residuals, remaining after
      surgery, may respond to radiotherapy, thereby promoting survival. The importance
      of radiotherapy for advanced ovarian cancer is controversial, and studies
      frequently show contradictory results. Two studies have shown the favorable role
      played by radiotherapy in consolidation treatment of patients if they become
      cancer-free at advanced stages. The role of radiotherapy in treating larger
      volumes of residual cancer has not been demonstrated, except for strictly
      palliative treatment.

PMID- 9154101
TI  - Hodgkin's disease.
AB  - This synthesis of the literature on radiotherapy for Hodgkin's Disease is based
      on 104 scientific articles, including 2 meta-analyses, 22 randomized studies, 5
      prospective studies, and 58 retrospective studies. These studies involve 38,362
      patients. The literature review clearly shows that radiotherapy is a cornerstone
      of treatment for localized Hodgkin's disease. At early stages, long-term survival
      is 80% to 90% when treatment is tailored to known prognostic factors. There is a
      tendency toward increased use of chemotherapy as additional treatment, however no
      evidence shows that it increases survival. To further improve survival following
      radiotherapy an attempt is being made to reduce long-term toxicity by better
      defining the patient groups who require lower radiation volumes, and delivering a
      dose that is as low as possible to avoid secondary solid tumors or delayed
      cardiopulmonary or gastrointestinal effects, while not jeopardizing therapeutic
      results. In advanced disease, radiotherapy may be needed as a complement to
      chemotherapy to effectively control bulky disease. For recurrent disease,
      radiotherapy may be considered as relapse treatment or additional therapy in
      conjunction with high-dose chemotherapy.

PMID- 9154102
TI  - Non-Hodgkin's lymphomas (NHL).
AB  - This synthesis of the literature on radiotherapy for non-Hodgkin's lymphomas is
      based on 158 scientific articles, including 16 randomized studies, 18 prospective
      studies, and 90 retrospective studies. These studies involve 14,137 patients. Non
      Hodgkin's lymphomas are highly radiosensitive, and local recurrence following
      radiotherapy is unusual. Radiotherapy probably cures approximately 50% of both
      low-grade and high-grade malignant NHL at stage I. Involved field is apparently
      sufficient, however, higher doses are required for high-grade malignant
      lymphomas. Chemotherapy is recommended for stage II. Consolidation radiotherapy
      after chemotherapy may increase the number of complete remissions. The value of
      adjuvant radiotherapy has not been confirmed. Radiotherapy plays a limited role
      at stages III and IV. Radiotherapy is clearly indicated for extranodal localized
      disease in the skin and in the orbit of the eye. It is important to identify
      groups and subgroups in whom radiotherapy alone is sufficient, ie, the risk for
      distant recurrence is small. MALT lymphoma belongs to this group. Radiotherapy is
      often valuable in palliative situations.

PMID- 9154103
TI  - Soft tissue sarcomas.
AB  - This synthesis of the literature on radiotherapy for sarcomas originating in the
      body's soft, supportive tissues, ie, muscle, connective tissue, and fatty tissue
      is based on 71 scientific articles, including 4 randomized studies, 5 prospective
      studies, and 26 retrospective studies. These studies involve 3,444 patients. Over
      90% of patients with soft tissue sarcomas in the arms and legs can be treated in
      a way that preserves the extremities. Subcutaneous and intramuscular sarcomas can
      be treated surgically with little functional loss or risk for local recurrence
      without adjuvant radiotherapy. To avoid amputation, surgery is often combined
      with radiotherapy for treatment of local relapse. Adequate surgical margins are
      usually difficult to achieve for head/neck tumors and retroperitoneal tumors, and
      therefore surgery is often combined with radiotherapy to reduce the risk for
      local relapse. Pre- and postoperative radiotherapy are similar. A disadvantage of
      preoperative radiotherapy is that it reduces the opportunity for exact diagnosis
      and determining morphobiologic sarcoma parameters. To further improve treatment
      results for advanced sarcomas, it is necessary to introduce other fractionation
      schedules, mainly hyperfractionation. This places greater demands on
      radiotherapy, mainly for staff resources. Combining radiotherapy and local
      intraarterial chemotherapy involves greater risks for complications and has not
      shown better treatment results than pre- or postoperative radiotherapy alone, and
      it is not recommended as standard treatment for soft tissue sarcomas.
      Intraoperative treatment methods should be targeted for further study and
      development.

PMID- 9154104
TI  - Bone sarcomas.
AB  - The literature on radiotherapy for sarcomas originating in bone is limited, and
      the disease is uncommon. Consequently, this review is based on only 28 scientific
      articles, including 6 randomized studies, I prospective study, and II
      retrospective studies. These studies involve 1,394 patients. Radiotherapy is of
      limited value for treating the primary tumors of osteosarcoma. The effects of
      prophylactic lung irradiation for treating osteosarcoma are unconfirmed.
      Radiotherapy represents an integrated component of primary treatment for Ewing's
      sarcoma, but different fractionation schedules should be assessed. Radiotherapy
      is of limited value in the treatment of chondrosarcoma.

PMID- 9154105
TI  - Skeletal metastases.
AB  - This synthesis of the literature on radiotherapy for skeletal metastases is based
      on 171 scientific articles, including 13 randomized studies, 24 prospective
      studies, and 79 retrospective studies. These studies involve 13054 patients.
      Radiotherapy has been well documented as a method for alleviating pain, but the
      mechanisms underlying this effect are largely unknown. When used for pain
      palliation, radiotherapy achieves freedom from pain, or substantial alleviation
      of pain in nearly all cases, with few side effects. Half-body irradiation is
      effective in treating multiple metastatic sites and should be considered for use
      more frequently. However, this increases the requirements on equipment,
      dosimetry, and hospital beds. Systemic radiotherapy with radionuclides may be
      indicated for generalized skeletal pain. The role of radiotherapy in preventing
      or healing fractures is not fully evaluated. Optimum dose levels and
      fractionation schedules have not been established. Early radiotherapy for spinal
      cord compression may prevent symptoms from worsening, but the effects on existing
      paralysis are modest.

PMID- 9154107
TI  - Radiotherapy for cancer. Quality of life.
AB  - This synthesis of the literature on the quality of life in relation to
      radiotherapy is based on 78 scientific articles, including 12 randomized studies,
      25 prospective studies, and 20 retrospective studies. These studies involve 9884
      patients. Radiotherapy is often organ-preserving, which inherently promotes a
      better quality of life. Many quality of life aspects related to radiotherapy have
      been studied, but seldom by prospective randomized studies that compare
      radiotherapy to other treatment (eg, surgery or chemotherapy). Radiotherapy
      involves numerous physical and psychological symptoms, mainly during the course
      of treatment. Examples include skin irritation and fatigue. Radiotherapy directed
      at the brain has delayed effects, in children treatment carries a substantial
      risk for lowering the IQ. The risk for encephalopathy in adults is probably
      underestimated. Patients with cancer in the head and neck may experience adverse
      side effects in the irradiated area long after the conclusion of radiotherapy.
      There are no confirmed differences in quality of life between breast cancer
      patients receiving adjuvant radiotherapy and those receiving chemotherapy.
      Impotency problems and urinary incontinence appear following radical surgery and
      radiotherapy for prostate cancer. The risk for delayed complications is low after
      radiotherapy for testicular cancer. Patients receiving radiotherapy for
      gynecologic cancers are often troubled by local side effects long after the
      conclusion of treatment.

PMID- 9154106
TI  - Transplantation of bone marrow and peripheral stem cells.
AB  - This synthesis of the literature on radiotherapy related to bone marrow
      transplantation is based on 59 scientific articles, including 5 randomized
      studies and 20 retrospective studies. These studies involve 2563 patients. Bone
      marrow transplantation is a rapidly expanding treatment method where whole-body
      irradiation can play an important role. The literature review reveals that
      treatment methods for whole-body irradiation are highly heterogeneous.
      Standardization would be desirable. Fractionated and single-dose, whole-body
      irradiation are probably of equal value when the dose and technique are optimal.
      Cataracts seem to be more common following a single dose. Fractionated treatment
      is more resource intensive, but less burdensome for patients. For advanced-stage
      leukemia and some other diseases, eg, myeloma, international experience has shown
      that a combined treatment strategy (high-dose cyclophosphamide and whole-body
      irradiation) is probably superior to chemotherapy (cyclophosphamide and busulfan)
      alone. For many other hematological malignancies at less advanced stages,
      conditioning methods are probably of equal value.

PMID- 9154108
TI  - Application of combinatorial library methods in cancer research and drug
      discovery.
AB  - Combinatorial chemistry is now considered as one of the most important recent
      advances in medicinal chemistry. There are five general approaches in
      combinatorial peptide library methods: biological libraries; spatially
      addressable parallel solid phase or solution phase libraries; synthetic library
      methods requiring deconvolution; the 'one-bead one-compound' library method; and
      synthetic library methods using affinity chromatography selection. Except for the
      biological library approach, which is limited to peptide libraries with
      eukaryotic amino acids, all the other four synthetic approaches are applicable to
      peptide, non-peptide oligomer or small molecule libraries. Although non-peptide
      or small molecule libraries are generally prepared by a synthetic approach,
      recent advances in biosynthetic methods using enzymes may enable one to prepare
      chemical libraries that are otherwise difficult to synthesize chemically. In the
      'one-bead one-compound' library method every member of the library is screened in
      parallel, but the chemical structure of the positive compound-bead has to be
      determined either directly or via an encoding strategy. A reliable high
      throughput biological assay is needed for a successful combinatorial library
      screen. Solid-phase binding or functional assays as well as solution phase assays
      have been used successfully in various library methods. There has been enormous
      progress in the technological advances of molecular biology and the fundamental
      understanding of the molecular basis of cancer in recent years. By applying
      combinatorial chemistry and computational chemistry to the many cancer targets
      that have recently been identified, it is hopeful that more potent, more specific
      and less toxic anti-cancer agents will be developed in the foreseeable future. In
      addition to being a great tool for drug discovery, combinatorial chemistry has
      also proven to be invaluable in basic research. A few specific examples of the
      applications of combinatorial chemistry in basic cancer research and drug
      discovery are described in this mini-review.

PMID- 9154109
TI  - Enediyne-lexitropsin DNA-targeted anticancer agents. Physicochemical and
      cytotoxic properties in human neoplastic cells in vitro, and intracellular
      distribution.
AB  - Two series of hybrids of a dynemicin A model and DNA minor groove binding
      lexitropsins were synthesized and their cytotoxic activities were investigated in
      a panel of human normal and malignant cell lines using a colorimetric assay.
      Adriamycin was used as a control. Several of the agents demonstrated cytotoxic
      activity, the extent of which varied with tumor type. IC50s of the hybrids ranged
      from approximately 14-48 microM following 96 h incubation in the presence of test
      compound. Intracellular distribution studies were facilitated through endogenous
      fluorescence of the compounds. Evidence of nuclear uptake of the hybrid agents
      was demonstrated by confocal laser scanning microscopy. The results warrant
      further development of DNA-targeted enediyne-lexitropsin hybrids as potential
      anticancer agents.

PMID- 9154111
TI  - Structural and functional relationships of toyocamycin on NPM-translocation.
AB  - Toyocamycin is an antitumor antibiotic which has a pyrrolo[2,3-D]pyrimidine
      aglycone with a -CN substituent on the 5-carbon. Treatment of HeLa cells with
      toyocamycin induces redistribution of the nuclear phosphoprotein
      nucleophosmin/B23 (NPM) from nucleoli to nucleoplasm (NPM-translocation) which
      can be detected by immunofluorescence. NPM-translocation is useful in showing
      drug effects and in detecting drug-resistant cancer cells. To study which
      structural features of toyocamycin are important for NPM-translocation, we used
      toyocamycin analogs in which the 5-position -CN was either deleted (tubercidin)
      or replaced with a -CONH2 (sangivamycin) or -C(NOH)NH2. HeLa cells were incubated
      with these analogs for 4 h and assayed for NPM-translocation by
      immunofluorescence. We found that the analog with the deletion of the -CN group
      (tubercidin) did not induce translocation while those with replacement of the -CN
      group with -CONH2 or -C(NOH)NH2 retained the NPM-translocation activity. When
      these or similar modifications were applied to 7-deazaguanosine, none of the
      guanosine analogs were effective. These results indicate that modifications at
      the 5-position of the pyrrolo[2,3-D]pyrimidine ring and a structure similar to
      adenine rather than guanine are essential for NPM-translocation. Since inhibition
      of RNA synthesis did not induce NPM-translocation, our results suggest that
      interference with NPM's binding in nucleoli by these analogs causes NPM
      translocation.

PMID- 9154110
TI  - Aniline mustard analogues of the DNA-intercalating agent amsacrine: DNA
      interaction and biological activity.
AB  - Two series of analogues of the clinical antileukemic drug and DNA-intercalating
      ligand amsacrine have been prepared, containing aniline mustard sidechains of
      varying reactivity, linked either at the 4-position of the intercalating acridine
      chromophore (type A) or at the 1'-position of the 9-anilino group (type B). DNase
      I footprinting assays showed that compounds of type B had stronger reversible
      binding to DNA than did compounds of type A. Compounds of each type showed
      similar patterns of alkylation-induced cleavage of DNA, and alkylate at the N7 of
      guanines in runs of guanines (similar to the pattern for untargeted mustards) as
      well as some adenines. Both classes of compounds crosslinked DNA, although those
      bearing relatively inactive mustards did so only at high drug/base pair ratios.
      However, while the patterns of DNA alkylation were broadly similar, the compounds
      were considerably more cytotoxic than analogous untargeted mustards. Comparison
      of their cytotoxicities in wild-type and DNA repair-deficient lines indicated
      this toxicity was due to DNA crosslinks (except for the least reactive SO2-linked
      mustards). The 4-linked analogues showed slightly higher in vivo antileukemic
      activity than the corresponding 1'-linked analogues.

PMID- 9154112
TI  - The in vitro biological activities of synthetic 18-O-methyl mycalamide B, 10-epi
      18-O-methyl mycalamide B and pederin.
AB  - Mycalamides A and B, which were originally isolated from a marine sponge, show
      close structural similarity to the insect toxin pederin, and exhibit potent
      cytotoxicity and antitumour activity. Detailed investigation of the clinical
      potential of these compounds has been hampered because they are available in only
      minute quantities from natural sources. We now describe the biological activities
      of 18-O-methyl mycalamide B, 10-epi-18-O-methyl mycalamide and pederin, all
      prepared by total synthesis. The activities of 18-O-methyl mycalamide B and
      pederin were virtually indistinguishable when evaluated in DNA or protein
      synthesis assays, and in cytotoxicity assays using human carcinoma cell lines
      (IC50s 0.2-0.6 nM). In all assays, 10-epi-18-O-methyl mycalamide B was 10(3)
      times less toxic than its diastereoisomer, demonstrating that the cytotoxicity of
      18-O-methyl mycalamide B is inseparable from its ability to inhibit protein
      synthesis. Short-term exposure of squamous carcinoma cells to 18-O-methyl
      mycalamide B or pederin caused an irreversible inhibition of cellular
      proliferation and induced cellular necrosis. In contrast, the antiproliferative
      effects of the compounds on human fibroblasts were reversible and there was no
      evidence of necrosis. Demonstration that 18-O-methyl mycalamide B and the
      synthetically less complex molecule, pederin, show some tumour cell toxicity
      indicates that this novel class of compounds should be subjected to preclinical
      evaluation.

PMID- 9154113
TI  - Report of the Third International Workshop on Human Chromosome 15 Mapping 1996.
      October 25-27, 1996 in Vancouver B.C., Canada.

PMID- 9154114
TI  - Molecular defects in alkaptonuria.
AB  - At the dawn of human genetics Sir Archibald Garrod used alkaptonuria as a
      paradigm to demonstrate the applicability of the Mendelian laws to men and to
      develop the concept of inborn errors of metabolism. The human cDNA for
      homogentisate 1,2 dioxygenase was identified due to its homology to the
      corresponding mouse enzyme and was screened for mutations in alkaptonuric
      patients from Slovakia. Homozygous mutations were found in four unrelated
      families and their segregation with the disease was demonstrated. One of the
      mutations, observed in two families, leads to a frame-shift and thus is unlikely
      to produce functional protein. The data formally establish the homogentisate 1,2
      dioxygenase gene (HGD) as the molecular cause of alkaptonuria and allow for the
      development of molecular carrier tests in populations at risk.

PMID- 9154115
TI  - Assignment of the genes for cellular retinoic acid binding protein 1 (CRABP1) and
      2 (CRABP2) to human chromosome band 15q24 and 1q21.3, respectively, by in situ
      hybridization.

PMID- 9154116
TI  - Assignment of the human creatine transporter type 2 (SLC6A10) to chromosome band
      16p11.2 by in situ hybridization.

PMID- 9154117
TI  - Analysis of ribosomal and alphoid repetitive DNA by fiber-FISH.
AB  - We have used fluorescence in situ hybridization to extended DNA fibers (fiber
      FISH) to analyse the alpha-satellite and rDNA arrays on a human chromosome 22.
      The rDNA could be seen as a string of signals spanning about 430 kb. The bulk of
      the alphoid DNA was found in a single large array of about 2.6 Mb.

PMID- 9154118
TI  - Mapping of the 8q12 translocation breakpoint to a 40-kb region in a pleomorphic
      adenoma with an ins(8;3)(q12;p21.3p14.1).
AB  - The translocation t(3;8)(p21;q12) is the most common chromosome abnormality
      observed in pleomorphic adenomas of the salivary glands. In this paper we
      describe the physical mapping of the breakpoints in an adenoma with a variant
      t(3;8), viz., an ins(8;3)(q12;p21.3p14.1). Using sequence-tagged sites (STSs)
      corresponding to landmarks within a previously identified yeast artificial
      chromosome (YAC) spanning the breakpoint in adenomas with t(3;8), cosmids
      isolated from a chromosome 8-specific cosmid library. The 8q12 insertion
      breakpoint was mapped by FISH to a 300-kb region flanked by MOS and a new STS,
      CH129. A cosmid within this region was shown to span the breakpoint. To test
      whether the recently identified FHIT gene, which maps to 3p14.2, was disrupted by
      the 3p rearrangement, we also isolated an FHIT YAC and mapped this YAC by FISH
      distal to the most proximal 3p breakpoint. In addition, RT-PCR analysis revealed
      only a normal-sized FHIT transcript, suggesting that FHIT is not affected by the
      3;8-rearrangement.

PMID- 9154119
TI  - Development and use of a microdissected swine chromosome 6 DNA library.
AB  - To facilitate the identification of microsatellite genetic markers from a single
      swine chromosome, chromosome microisolation and microcloning have been used to
      generate a swine chromosome 6-specific DNA library. Ten copies of swine
      chromosome 6 were scraped from metaphase spreads, ligated to custom-prepared
      adaptors, and amplified by PCR. The purity of the amplified product was verified
      by fluorescent in situ hybridization. The utility of the chromosome painting
      probe for heterologous painting was demonstrated and confirmed that swine
      chromosome 6 is syntenic to human chromosomes 1p and 19q. A small insert genomic
      library of 1.39 x 10(6) clones was generated from the PCR-amplified chromosome 6
      genomic DNA and screened for (GT)n microsatellite genetic markers. Nine (GT)n
      microsatellite markers were developed and genotyped on a Yorkshire x Meishan
      swine reference family. All nine markers genetically mapped to chromosome 6,
      confirming the purity of the microisolation method. The method used here should
      be adaptable to the microdissection of subchromosomal regions of not only the
      swine genome but also other livestock genomes.

PMID- 9154120
TI  - Assignment of v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2
      (ERBB2) to human chromosome band 17q21.1 by in situ hybridization.

PMID- 9154121
TI  - Abnormal structure of the Y chromosome detected in bovine gonadal hypoplasia (XY
      female) by FISH.
AB  - The structure of the Y chromosome was investigated by FISH and G banding in 3
      cases of bovine XY females shown by PCR to lack the SRY gene. Although 2
      different repeat-DNA sequences (BC1.2 and btDYZ-1) hybridized to the short arm of
      the Y chromosome in a normal bull, they hybridized to both arms of the Y
      chromosome in the XY females. In the Y chromosome from XY females, only the
      centromeric region was darkly stained by G banding, in comparison with dark
      staining on the long arm of a normal Y chromosome. From the results obtained, it
      seemed that the Y chromosome from the XY females was structurally abnormal,
      namely an isochromosome with an identical short arm. Our results also confirm
      that SRY is located on the long arm of the Y chromosome in bovine.

PMID- 9154122
TI  - Assignment of the gene for human tetranectin (TNA) to chromosome 3p22-->p21.3 by
      somatic cell hybrid mapping.
AB  - Tetranectin is a plasminogen-binding protein that is induced during the
      mineralization phase of osteogenesis. By screening a human chromosome 3 somatic
      cell hybrid mapping panel, we have localized the human tetranectin gene (TNA) to
      3p22-->p21.3, which is distinct from the loci of two human connective tissue
      disorders that map to the short arm of chromosome 3, MFS2 and LRS1.

PMID- 9154123
TI  - Assignment of the human TAFII30 gene (TAF2H) to human chromosome band 11p15.3
      using somatic cell hybrids.

PMID- 9154124
TI  - Assignment of PTK7 encoding a receptor protein tyrosine kinase-like molecule to
      human chromosome 6p21.1-->p12.2 by fluorescence in situ hybridization.

PMID- 9154125
TI  - Assignment of a novel cysteine proteinase inhibitor (CST6) to 11q13 by
      fluorescence in situ hybridization.

PMID- 9154126
TI  - Assignment of rat thromboxane synthase gene (Tbxas) to chromosome 4q21-->q22 by
      fluorescence in situ hybridization.
AB  - Thromboxane A2 plays physiological and pathophysiological roles in many tissues.
      We isolated a cDNA for rat thromboxane synthase from the kidney and here show the
      location of rat thromboxane synthase gene (Tbxas) on rat chromosome 4q21-->q22 by
      fluorescence in situ hybridization to metaphase chromatin of rat lymphocytes.

PMID- 9154127
TI  - FISH localization of the human Y-homolog of protein kinase PRKX (PRKY) to Yp11.2
      and two pseudogenes to 15q26 and Xq12-->q13.
AB  - Recently, we reported the isolation of a new subfamily of serine-threonine
      protein kinases. This subfamily was shown to consist of at least four members.
      Sequencing and FISH mapping of all 4 members now reveals that the Y-homolog
      (PRKY) of the previously mapped PRKX gene (Xp22.3) is located in Yp11.2, in close
      vicinity to AMELY. The other two copies reside on Xq12-->q13 (PRKXP2) and 15q26
      (PRKXP1, containing CA repeat STS D15S87) and represent pseudogenes.

PMID- 9154129
TI  - Instability of CHO chromosomes containing interstitial telomeric sequences
      originating from Chinese hamster chromosome 10.
AB  - We identified a marker chromosome in the CHO K1 cell line containing
      amplifications of interstitial telomeric sequences originating from Chinese
      hamster chromosome 10. Analysis of the progression of this chromosome in two
      subclones of CHO K1 revealed sensitivity of one amplicon to chromosome breakage,
      resulting in telomere function at the break site. In addition, two more marker
      chromosomes, both containing amplifications of interstitial telomeric sequences
      from chromosome 10, were formed during karyotypic evolution of the CHO K1
      subclones. The presence of some of the marker chromosomes was also identified in
      the radiosensitive xrs 5 cell line derived from CHO K1. These results indicate
      instability of CHO K1 chromosomes containing interstitial telomeric sequences
      originating from Chinese hamster chromosome 10.

PMID- 9154128
TI  - The gene cluster containing the LCAT gene is conserved between human and pig.
AB  - A pooled DNA probe from P1 artificial chromosome clones (PACs) containing the
      human lecithin:cholesterol acyl transferase (LCAT) gene cluster was used in
      fluorescence in situ hybridization (FISH) experiments assigning the genes to pig
      chromosome 6p13. In addition, probes derived from the coding regions in the human
      gene cluster were used in long range mapping experiments to show that the overall
      structures of the human and porcine LCAT gene clusters are identical. Both the
      linear order and the close physical distance of five apparently unrelated genes
      have been maintained throughout 90 million years of divergent evolution between
      human and pig. The extremely dense clustering of the genes in the LCAT gene
      cluster suggests that this gene organization has biological significance. The
      conservation of the gene cluster between human and pig supports this suggestion.

PMID- 9154130
TI  - Topoisomerase II inhibition in mitosis produces numerical and structural
      chromosomal aberrations in human fibroblasts.
AB  - We investigated the effects of treatment of mitotic human fibroblasts with the
      topoisomerase II inhibitor etoposide (VP-16) on chromosome segregation at
      anaphase and the genetic consequence to daughter cells of topoisomerase
      inhibition during mitosis. The most striking effect of VP-16 treatment during
      mitosis was the production of anaphase cells with several entangled chromosomes
      (catenated anaphase cells). To analyze the effects of sister chromatid catenation
      at anaphase on the daughter cells, several interphase methodologies were applied
      to binucleated human fibroblasts that were blocked during cytokinesis. Post
      treatment of mitotic cells with the cytokinesis inhibitor cytochalasin-B
      maintains the reciprocal products of a mitotic division in the same cytoplasm,
      allowing the distribution of whole chromosomes or chromosome fragments in
      daughter nuclei or micronuclei to be followed. The presence of micronuclei
      containing kinetochores, as detected by antikinetochore staining, suggested that
      VP-16 treatment during mitosis induces chromosome loss in binucleated
      fibroblasts. Induction of aneuploid cells for chromosomes 7 and 11 was observed
      by double in situ hybridization using chromosome-specific alphoid probes in
      binucleated fibroblasts. In addition, double in situ hybridization with adjacent
      alphoid and classical satellite DNA probes to chromosome 1 demonstrated that both
      numerical and structural aberrations contribute to the genetic effects of
      topoisomerase II inhibition in mitosis.

PMID- 9154131
TI  - Characterization of a de novo unbalanced chromosome rearrangement by comparative
      genomic hybridization and fluorescence in situ hybridization.
AB  - Fluorescence in situ hybridization (FISH) has proven useful for the
      identification of chromosomal material of unknown origin. More recently,
      comparative genomic hybridization (CGH) has been used to identify deletions and
      amplifications, particularly in neoplastic samples. Here, we describe the
      combined use of CGH and FISH to identify the origin of a de novo unbalanced
      translocation in a newborn with multiple congenital anomalies. GTG banding of
      metaphases from cultured lymphocytes showed an unbalanced karyotype, with extra
      material on a chromosome 5: 46,XX,add(5)(q35). Parental karyotypes were both
      normal. CGH revealed the additional material was from distal 11q (11q23-->'qter).
      This finding was confirmed by FISH with a whole chromosome paint for chromosome
      11. Based on the CGH and FISH analyses, the proband's karyotype was therefore
      46,XX,der(5)t(5;11)(q35.2; q23.2).ish der(5)(wcp11+). This case demonstrates the
      efficient use of CGH and confirmatory FISH for the identification of chromosomal
      material of unknown origin.

PMID- 9154132
TI  - Construction of chicken x human microcell hybrids for human gene targeting.
AB  - Human chromosomes 1, 2, 3, and 11 were tagged with pSV2 neo and transferred via
      microcell fusion from mouse A9 human monochromosomal hybrids to a chicken pre-B
      cell line, DT40, proficient for homologous recombination. Hybrids containing two
      copies of human chromosome 11 were transfected with targeting vectors containing
      a mammalian selectable gene with either the D11S16 or HRAS genomic sequences
      corresponding to two different chromosome 11 loci. Analysis of stable
      transfectants showed a high frequency (approximately 80%) of targeted integration
      of these constructs into each of the homologous loci of human chromosome 11 in
      DT40 hybrids. The results suggest that any human genomic sequences on human
      chromosomes transferred into DT40 cells could be targeted at high frequency,
      thereby allowing for subsequent modification of human genes and chromosomes.

PMID- 9154133
TI  - Nucleolar size and shape is sexually dimorphic in neurons of the lateral
      magnocellular nucleus of the anterior neostriatum (LMAN) in birds.
AB  - The lateral magnocellular nucleus of the anterior neostriatum (LMAN) in birds
      plays an important role in songlearning processes. Recently, it has been shown
      that structural changes at the cellular level in males are causally related to
      vocal learning. Whereas males sing, females do not. This sexual difference in
      behavior is also reflected in sexual differences in the neuronal structure in
      adult birds, with males having larger neuronal somata than do females. In the
      present report, the size and shape of the nucleoli were investigated to determine
      if sexual differences were also present at the nucleolar level. The data
      demonstrated a strong sexual difference in nucleolar size in both juvenile and
      adult birds, the cross-sectional area of the nucleoli being significantly larger
      in males than in females (30% and 50% larger in juvenile and adult birds,
      respectively). This difference between males and female finches was also
      reflected by the cross-sectional area of a specific type of nucleolus exhibiting
      a central light area. In both sexes, nucleoli exhibiting a central light area
      were significantly larger in juvenile and adult birds than nucleoli that lacked a
      central light area. The percentage of neurons exhibiting a central light area was
      higher in adult males than in adult females, but not in juvenile birds. The time
      course of development of nucleoli exhibiting a central light area in males was
      very similar to the development of neuronal somata size in LMAN neurons. The
      larger size of the nucleoli in LMAN neurons in males and the developmental
      changes in the incidence of nucleoli exhibiting a central light area may be
      indicative of a high level of ribosome production necessary for song-learning
      processes to occur.

PMID- 9154134
TI  - Isolation and mapping of karyopherin alpha 3 (KPNA3), a human gene that is highly
      homologous to genes encoding Xenopus importin, yeast SRP1 and human RCH1.
AB  - From a human fetal-brain cDNA library, we isolated and characterized a novel gene
      (KPNA3) encoding a protein highly homologous to certain nuclear transport
      proteins of Xenopus and human. The complete cDNA clone, designated karyopherin
      alpha 3, contained an open reading frame of 1,563 nucleotides encoding 521 amino
      acids. The predicted amino acid sequence showed 48%, 45% and 48% identity with
      Xenopus importin, yeast SRP1 and human RCH1, respectively. The similarities among
      these proteins suggest that karyopherin alpha 3 may be involved in the nuclear
      transport system. Eight repeats of the arm motif were well conserved among these
      proteins. The N-terminal region of the predicted karyopherin alpha 3 product was
      highly basic and the C-terminal region was strongly acidic. A 4.3-kb transcript
      was expressed in all adult human tissues examined by Northern blotting. The cDNA
      clone was assigned to chromosome band 13q14.3 by fluorescence in situ
      hybridization.

PMID- 9154135
TI  - AluI in situ digestion of human alphoid and classical satellite DNA regions: high
      resolution digital image analysis of FISH signals from condensed and extended
      chromatin.
AB  - Human lymphocyte chromatin either extended or condensed in interphase nuclei and
      chromosomes was in situ digested by the restriction endonuclease AluI and then
      hybridized with alphoid probes specific for chromosome 1 (D1Z5 locus), for
      chromosome X (DXZ1 locus), and with a classical satellite DNA probe specific for
      chromosome 9 (D9Z1 locus). Fluorescent hybridization signals were quantified by
      digital analysis of high-resolution images obtained by a Photo-CD system in an
      attempt to analyze the differential DNA removal produced by AluI in specific
      repetitive DNA sequences with known restriction site frequency and distribution.
      The analysis of area and average pixel grey count of hybridization signals
      suggests that the greater the degree of chromatin stretching, the higher the
      accessibility of the probe and/or reporter molecules to the target. Nevertheless,
      this greater hybridization efficiency does not result in a higher fluorescence
      intensity due to dispersion of individual signals. Specific repetitive DNA at
      D9Z1 locus (classical) remained impervious to digestion, while that at DXZ1
      (alphoid) was extensively removed, according to the frequency and distribution of
      restriction sites. Nevertheless, though the restriction sites were at least as
      frequent as at the DXZ1 locus, DNA at the D1Z5 locus (alphoid) was only partially
      removed. This indicates that chromatin organization within the C-band partially
      prevents extraction of alphoid sequences, supporting the hypothesis that alphoid
      DNA sequences are differentially organized among chromosomes. Overall, the same
      results were obtained from condensed and extended chromatin, suggesting that
      higher-order chromatin organization does not influence the in situ DNA cleavage
      and removal by AluI.

PMID- 9154136
TI  - The rat 5S rRNA bona fide gene repeat maps to chromosome 19q12-->qter and the
      pseudogene repeat maps to 12q12.
AB  - The bona fide 5S rRNA genes in the rat are found in a 1.8-kb tandem repeat and
      the pseudogenes occur in a 2.5-kb tandem repeat. Three bona fide 5S rRNA genes
      and one gene variant with one base substitution in the coding region were
      isolated from the 1.8-kb repeat. Six pseudogenes were isolated from the 2.5-kb
      repeat. The total number of genes/gene variants/pseudogenes is 700-1200 copies
      per haploid genome, and the pseudogene repeat contains about 50% more 5S rDNA
      related sequences compared with the bona fide gene repeat. Various well-defined
      5' - and 3'-flanking sequences of the bona fide gene and of the pseudogene were
      used for in situ hybridization to metaphase chromosomes. The results showed that
      the bona fide 5S rRNA gene repeat Rn5s maps to chromosome 19q12 and the
      pseudogene repeat Rn5sp maps to 12q12.

PMID- 9154137
TI  - Assignment of TRIO, the Trio gene (PTPRF interacting) to human chromosome bands
      5p 15.1-->p 14 by in situ hybridization.

PMID- 9154138
TI  - Mapping in pig of genes involved in sexual differentiation: AMH, WT1, FTZF1,
      SOX2, SOX9, AHC, and placental and embryonic CYP19.
AB  - Intersexuality has been reported in pigs and investigations are in progress to
      identify and physically map the genes involved in sex-reversal. In this study we
      have mapped on porcine chromosomes seven genes which might be implicated in this
      developmental pathway. Four genes were mapped by radioactive in situ
      hybridization: AMH (Anti-Mullerian Hormone) and WT1 (Wilms' Tumor gene 1) were
      both mapped to pig chromosome 2 (SSC2) in the q14-->q21 and p14-->q11 regions,
      placental CYP19 (cytochrome P450, subfamily XIX) and FTZF1 (fushi tarazu factor
      [Drosophila] homolog 1, alias SF1 [steroidogenic factor 1]) to pig chromosome 1
      (SSC1) in the q14-->q17 and q210-->q211 regions respectively. Four other genes
      were regionally located by PCR analysis on a cytogenetically characterized
      porcine somatic cell hybrid panel: a second CYP19 gene (expressed in embryo) was
      mapped to porcine 1q12-->q17, AHC (alias DAX1, adrenal hypoplasia congenital) to
      porcine Xp24, SOX2 and SOX9 (SRY sex determining region Y-box 2 and 9) to 13q23-
      >q41 and 12p13-->p11 respectively. These results are in global agreement with
      mapping data available in other mammalian species.

PMID- 9154139
TI  - DNA double-strand break distributions in X-ray and alpha-particle irradiated V79
      cells: evidence for non-random breakage.
AB  - Many studies have shown that with increasing LET of ionizing radiation the RBE
      (relative biological effectiveness) for dsb (double strand breaks) induction
      remains around 1.0 despite the increase in the RBE for cell killing. This has
      been attributed to an increase in the complexity of lesions, classified as dsb
      with current techniques, at multiply damaged sites. This study determines the
      molecular weight distributions of DNA from Chinese hamster V79 cells irradiated
      with X-rays or 110 keV/micron alpha-particles. Two running conditions for pulsed
      field gel-electrophoresis were chosen to give optimal separation of fragments
      either in the 225 kbp-5.7 Mbp range or the 0.3 kbp to 225 kbp range. Taking the
      total fraction of DNA migrating into the gel as a measure of fragmentation, the
      RBE for dsb induction was less than 1.0 for both molecular weight regions
      studied. The total yields of dsb were 8.2 x 10(-9) dsb/Gy/bp for X-rays and 7.8 x
      10(-9) dsb/Gy/bp for alpha-particles, measured using a random breakage model.
      Analysis of the RBE of alpha-particles versus molecular weight gave a different
      response. In the 0.4 Mbp-5.7 Mbp region the RBE was less than 1.0; however, below
      0.4 Mbp the RBE increased above 1.0. The frequency distributions of fragment
      sizes were found to differ from those predicted by a model assuming random
      breakage along the length of the DNA and the differences were greater for alpha
      particles than for X-rays. An excess of fragments induced by a single-hit
      mechanism was found in the 8-300 kbp region and for X-rays and alpha-particles
      these corresponded to an extra 0.8 x 10(-9) and 3.4 x 10(-9) dsb/bp/Gy,
      respectively. Thus for every alpha-particle track that induces a dsb there is a
      44% probability of inducing a second break within 300 kbp and for electron tracks
      the probability is 10%. This study shows that the distribution of damage from a
      high LET alpha-particle track is significantly different from that observed with
      low LET X-rays. In particular, it suggests that the fragmentation patterns of
      irradiated DNA may be related to the higher-order chromatin repeating structures
      found in intact cells.

PMID- 9154141
TI  - Time-resolved EPR studies on the reaction rates of peroxyl radicals of
      poly(acrylic acid) and of calf thymus DNA with glutathione. Re-examination of a
      rate constant for DNA.
AB  - Electron paramagnetic resonance (EPR) signals of peroxyl radicals of poly(acrylic
      acid), PAA, and of single- and double-stranded DNA were generated at 293 K and pH
      6.6 by in situ photolysis of O2-saturated aqueous solutions containing the
      macromolecules and H2O2. From time-resolved EPR measurements upper limits for the
      rate constants of reaction of glutathione (GSH) with the peroxyl radicals of PAA
      [kb < or = (0.8 +/- 0.2) x 10(2) dm3 mol-1S-1] and of single- and double-stranded
      DNA from calf thymus [kb < or = (2 +/- 2) x 10(2) dm3 mol-1S-1] were determined.
      The low value of kb for reaction of GSH with DNA peroxyl radicals is in agreement
      with the observed lack of protective effect of the thiol in radiation-induced DNA
      strand break reactions (Liphard et al. 1990).

PMID- 9154140
TI  - In vitro rejoining of double strand breaks induced in cellular DNA by bleomycin
      and restriction endonucleases.
AB  - We have previously described a cell-free assay that can be employed to study
      rejoining of radiation-induced DNA double-stranded breaks (dsb) in 'naked' DNA
      prepared from agarose-embedded cells using an extract of HeLa cells as a source
      of enzymes. Rejoining of dsb in this assay is absolutely dependent on cell
      extract and proceeds, under optimal reaction conditions, to an extent and with
      kinetics similar to those observed in intact cells. Here, we extend these
      experiments and demonstrate that the assay also supports rejoining of bleomycin
      and restriction endonuclease-induced dsb, agents that generate dsb with known
      ends. Rejoining of bleomycin-induced dsb proceeds to an extent and with kinetics
      similar to those observed with radiation-induced dsb. The kinetics of rejoining
      of restriction endonuclease-induced dsb are also similar to those of radiation
      induced dsb. However, more and more dsb remain unrejoined as the extent of DNA
      fragmentation increases when enzymes cutting the DNA at frequent intervals are
      used. Dsb with blunt ends are rejoined with a similar efficiency to dsb with
      cohesive ends. Rejoining of restriction endonuclease-induced dsb is, in the
      presence of cell extract, more efficient than in the presence of T4 DNA ligase,
      suggesting the action in the overall reaction of activities in addition to DNA
      ligases. The experiments presented generalize the utility of the assay in
      studying the enzymology of dsb rejoining after treatment with radiomimetic drugs
      and restriction endonucleases and should be useful in the elucidation of the
      enzymatic requirements of dsb repair.

PMID- 9154142
TI  - Secondary radical attack on DNA nucleotides: reaction by addition to DNA bases
      and abstraction from sugars.
AB  - In this work radicals generated by dissociative electron attachment to
      iodoacetamide (H2NCOCH2.) and 6-chloromethyluracil (U5CH2.) are suggested to
      react with DNA nucleotides in frozen aqueous solutions via either hydrogen
      abstraction or addition to the double bonds of the bases. Methyl hydrogens of TMP
      are the preferential sites of the attack by H2NCOCH2. radical. For dCMP the C1'
      site on the sugar group is found to be the preferred site of hydrogen abstraction
      by H2NCOCH2. while for dGMP and to a lesser extent dAMP attack at the C8 position
      of the purine ring is found to be competitive with sugar attack. In general
      allylic U6CH2. and U5CH2. radicals are found to be poor hydrogen abstractors and
      the only reaction pathway found is the addition to double bonds at C6 in thymine
      and C8 in adenine and guanine. Whereas, the cytosine 5,6 double bond appears to
      be unreactive towards addition at low temperatures. Some evidence is found for
      sugar radical addition to the adenine C8 position.

PMID- 9154143
TI  - The effect of serum albumin on the radiolysis of DNA studied by constant field
      electrophoresis and compared to alterations caused by low molecular weight OH.
      scavengers.
AB  - After radiolysis of calf thymus DNA in 10(-2) mol dm-3 phosphate buffer at pH7
      under N2, N2O and air the yields of double-strand breaks (dsb) have been
      determined by constant field electrophoresis. Double-strand (dsb) breaks were
      formed according to a linear-quadratic relationship with dose showing a lower G
      value under aerobic than under anaerobic conditions (G (air) = 1.4 nmolJ-1; G
      (N2) = 2.1 nmolJ-1; G (N2O) = 4.9 nmolJ-1). To test the reliability of this
      system the effect of low molecular weight OH. scavengers which were already used
      in comparable work with plasmid DNA were studied. The results with plasmid DNA
      and calf thymus DNA obtained by different techniques of electrophoresis agreed
      quite well. Under N2 more protection was obtained with ethanol than with DMSO or
      with t-butanol. Under air, double-strand breakage was further decreased and
      reached the same level with all of these scavengers. Furthermore the constant
      field electrophoresis gives similar results as the low-angle light scattering
      technique for radiation induced double strand breakage of calf thymus DNA. When
      BSA was used at the same scavenger capacity as the low molecular weight
      scavengers, the protection against double strand breakage was less if radiolysis
      was carried out in the presence of proteins. Under anaerobic conditions the
      protection factor was 13 in the presence of BSA, while with DMSO or t-butanol
      this factor was about 100 and with ethanol 300. In contrast to the low molecular
      weight OH. scavengers oxygen enhanced radiation-induced double-strand breakage
      with BSA. It is assumed that protein peroxyl radicals may cause strand breakage.

PMID- 9154144
TI  - Radiation-induced apoptosis in the rat spinal cord: lack of equal effect per
      fraction.
AB  - This study assessed the apoptotic response in the rat spinal cord following split
      dose and fractionated irradiation. The cervical spinal cord (C2-T2) of adult
      female Fisher 344 rats was irradiated with a single, two, three or four daily
      fractions of 8 Gy, or two doses of 8 Gy separated by an interval of 0, 1, 2 or 4
      h, or 1, 2, 3, 6, 10, 14, 28 or 63 days between two doses. Animals were
      sacrificed at 0, 4, 8, 12 and 24 h after each final 8-Gy dose, and the percentage
      of apoptotic glial cells was scored histologically according to specific
      morphological features of apoptosis. After a single dose of 8 Gy, the percent of
      apoptotic glial cells increased at 4 h (0.29 +/- 0.02%), peaked at 8 h (1.04 +/-
      0.06%) and returned to the baseline by 24 h (0.05 +/- 0.01%). The total apoptotic
      yield (TAY) per spinal cord section over a 24-h period after a single 8-Gy dose
      was 9.04 +/- 0.34%. The second, third and fourth 8-Gy fractions given once daily
      gave TAY = 3.66 +/- 0.22, 2.10 +/- 0.16 and 1.42 +/- 0.17% respectively, an
      apoptotic response that was significantly decreased compared with the initial 8
      Gy fraction (p < or = 0.01). Irrespective of the interfraction interval, two
      fractions of 8 Gy always induced a greater apoptotic response than that from a
      single 16 Gy (8 Gy-0 h-8 Gy, p < or = 0.008). TAY from the second 8-Gy dose given
      at 0, 1, 2, 4, 24 and 48 h was 0.93 +/- 0.03, 2.32 +/- 0.10, 3.26 +/- 0.10, 2.57
      +/- 0.11, 3.67 +/- 0.22 and 3.48 +/- 0.13% respectively versus 9.04 +/- 0.34%
      after the initial 8 Gy (p < or = 0.001). TAY = 7.01 +/- 0.33% from the second 8
      Gy dose given at an interval of 3 days was significantly greater than that given
      at 1 or 2 days (p < 0.0001), but significantly less than that of 9.84 +/- 0.33%
      given at 14 days (p = 0.0003), suggesting recovery of the apoptotic response
      occurring at 3 days and completed at 14 days after the initial 8 Gy dose. For
      radiation-induced apoptosis in the rat spinal cord, we conclude that the concept
      of equal effect per fraction is not applicable, and that split doses are more
      effective than the same dose given as a single fraction.

PMID- 9154145
TI  - Medium from irradiated human epithelial cells but not human fibroblasts reduces
      the clonogenic survival of unirradiated cells.
AB  - The results reported in this paper show a highly significant fall in cloning
      efficiency in unirradiated normal and malignant epithelial cell lines receiving
      medium from irradiated cultures. Medium irradiated in the absence of cells had no
      effect nor did irradiated medium from a fibroblast line, but irradiated medium
      from epithelial cells had an extremely toxic effect on unirradiated fibroblasts.
      Cells from four different cell lines were seeded, using standard techniques, 6 h
      prior to irradiation with cobalt 60 (Co60). At various times ranging from 1-60 h
      after irradiation, medium was removed, passed through a 0.22 mu filter and then
      used to replace the medium from parallel cultures seeded at cloning densities
      which had not been irradiated. The effect produced by the epithelial cell
      cultures was dependent on the cell number present at the time of irradiation,
      suggesting that a cell-derived factor is involved. The effect could be observed
      using medium taken from irradiated cultures as soon as 30 min/post irradiation.
      Examination of unirradiated cultures 48 h after receiving irradiated medium
      revealed the presence of high numbers of apoptotic bodies and other morphological
      evidence suggesting apoptosis may be a prominent mechanism of cell death
      responsible for the reduced cloning efficiency.

PMID- 9154146
TI  - Flow cytometry as a quantitative and sensitive method to evaluate low dose
      radiation induced apoptosis in vitro in human peripheral blood lymphocytes.
AB  - Human peripheral blood lymphocytes, irradiated in vitro, die by an apoptotic
      process. The number of apoptotic cells after in vitro gamma-irradiation (0, 0.1,
      0.2, 1, 2 and 5 Gy) was measured by flow cytometry using Annexin V and DiOC6 (a
      cationic dye) after 24 and 48 h incubation. The mean dose-response curves for
      apoptosis of six healthy volunteers obtained with both methods were steep below 1
      Gy and flatter at higher doses. A slightly higher number of apoptotic cells was
      observed with DiOC6, compared to Annexin V. This can be assigned to a minor DiOC6
      int/PI- population. Forty-eight hour cultures contained higher numbers of
      apoptotic cells compared with 24 h cultures. For both culture times, DiOC6 and
      Annexin V detected a statistically significant difference between a control
      sample and a 0.1 Gy irradiated one, illustrating the high sensitivity of the
      methods.

PMID- 9154147
TI  - Biological dosimetry in simulated in vitro partial irradiations.
AB  - The assessment by biological dosimetry of the dose received in cases of partial
      body exposure to ionizing radiation can be underestimated because irradiated
      lymphocytes are mixed with non-irradiated ones. To determine if the exposure
      affects the whole body or only part of it, it may be useful to know the
      distribution of cells with more than one dicentric chromosome. We established a
      dose-effect calibration curve for X-rays by analysis of chromosome aberrations.
      Moreover, in the present work, 20 partial irradiations for four different doses
      of X-rays (2, 3, 4 and 5 Gy) have been simulated by mixing irradiated and non
      irradiated blood in different proportions. In all cases, the 95% confidence
      intervals of the estimated dose included the real dose of irradiation. However,
      some difficulties were found for the estimation of the fraction of irradiated
      cells. In the present study, D0 = 3.8 allows to obtain the best fit between the
      estimated and the real fraction of irradiated cells.

PMID- 9154148
TI  - Sialochemical profile of X-irradiated major salivary glands in the rat.
AB  - The purpose of this study was to examine various sialochemical parameters in
      parotid (P) and submandibular (SM) secreted saliva of irradiated rats. Various
      doses of radiation from 2.5 to 15 Gy were administered to the head and neck
      region and the saliva was evaluated for its amylase activity and the
      concentration of sodium (Na), potassium (K) and total protein. Saliva samples
      containing equal amounts of proteins were also electrophoresed on separatory SDS
      gels, silver-stained and examined for possible qualitative alterations. The total
      protein concentrations of P saliva showed a radiation dose-dependent reduction at
      3 days and 3 and 9 months following 15 Gy of 93%, 82% and 73% (p < 0.01),
      respectively. Forty days after the 15 Gy irradiation the reduction was not as
      severe (55%, NS). Three and 40 days post 15 Gy, amylase activity demonstrated a
      similar pattern of reduction, 98% and 89% (p < 0.01), respectively. In contrast
      to the P, no quantitative changes in the protein concentrations of the SM saliva
      were detected. As for the qualitative profiles of separated proteins, no
      radiation-induced changes were found for either P or SM at 3 and 40 days or 3 and
      9 months, as compared with controls. The electrolyte concentrations were found to
      be flow-rate dependent. The Na concentrations of P saliva at 3 and 40 days
      following 15 Gy were reduced by 65% and 83% (p < 0.01), respectively. For SM
      saliva, the Na concentrations were reduced at 40 days by 58% (p < 0.05). The K
      concentration of P saliva increased at 40 days by 79% (p < 0.05). The data
      suggest that the various observed sialochemical changes could result from a
      reduction in the salivary flow rate and/or the number of surviving, normally
      functioning parenchymal cells. Thus, it is suggested that no salivary
      compositional alterations were directly induced by radiation but were secondary
      effects.

PMID- 9154149
TI  - Comments on the paper: the ATM gene and the radiobiology of ataxia
      telangiectasia.

PMID- 9154150
TI  - Efficient immunocytochemical labeling of leukocyte microtubules with
      FluoroNanogold: an important tool for correlative microscopy.
AB  - We tested the immunoprobe FluoroNanogold (FNG) for its utility as an
      immunocytochemical labeling reagent. This immunoprobe consists of a 1.4-nm gold
      particle to which a specific Fab' fragment and a fluorochrome are conjugated. We
      employed the microtubules (MTs) of human phagocytic leukocytes as a model system
      for testing the usefulness of FNG as a secondary antibody for
      immunocytochemistry. We show that these fluorescently labeled ultrasmall
      immunogold particles are very efficient for labeling MTs in these cells. The
      signal from FNG can be detected directly by fluorescence microscopy or indirectly
      by other modes of optical microscopy and electron microscopy, after silver
      enhancement of the gold. The spatial resolution of immunolabeled MTs obtained
      with FNG and silver enhancement was comparable to that of conventional
      immunofluorescence detection. Colloidal gold (5-nm and 10-nm in diameter), on the
      other hand, failed to label MTs in cells prepared in a similar manner. This
      difference in labeling was due in large part to greater penetration of 1.4-nm
      gold into aldehyde-fixed cells than either 5-nm or 10-nm gold particles. The
      fluorescent 1.4-nm immunoprobe was shown to be an important new tool for general
      use in correlative microscopy.

PMID- 9154151
TI  - Ectopic expression of SPARC in Xenopus embryos interferes with tissue
      morphogenesis: identification of a bioactive sequence in the C-terminal EF hand.
AB  - SPARC is a matricellular Ca(2+)-binding glycoprotein that exhibits both
      counteradhesive and antiproliferative effects on cultured cells. It is secreted
      by cells of various tissues as a consequence of morphogenesis, response to
      injury, and cyclic renewal and/or repair. In an earlier study with Xenopus
      embryos we had shown a highly specific and regulated pattern of SPARC expression.
      We now show that ectopic expression of SPARC before its normal embryonic
      activation produces severe anomalies, some of which are consistent with the
      functions of SPARC proposed from studies in vitro. Microinjection of SPARC RNA,
      protein, and peptides into Xenopus embryos before endogenous embryonic expression
      generated different but overlapping phenotypes. (a) Injection of SPARC RNA into
      one cell of a two-cell embryo resulted in a range of unilateral defects. (b)
      Precocious exposure of embryos to SPARC by microinjection of protein into the
      blastocoel cavity was associated with certain axial defects comparable to those
      obtained with SPARC RNA. (c) SPARC peptides containing follistatin-like and
      copper-binding sequences were without obvious effect, whereas SPARC peptide 4.2,
      corresponding to a disulfide-bonded, Ca(2+)-binding domain, was associated with a
      reduction in axial structures that led eventually to complete ventralization of
      the embryos. Histological analysis of ventralized embryos indicated that the
      morphogenetic events associated with gastrulation might have been inhibited.
      Microinjection of other Ca(2+)-binding glycoproteins, such as osteopontin and
      bone sialoprotein, resulted in phenotypes that were unique. We probed further the
      structural correlates of this region of SPARC in the context of tissue
      development. Co-injection of peptide 4.2 with Ca2+ or EGTA, and injection of
      peptide 4.2K (containing a mutated consensus Ca(2+)-binding sequence),
      demonstrated that the developmental defects associated with peptide 4.2 were
      independent of Ca2+. However, the disulfide bridge in this region of SPARC was
      found to be critical, as injection of peptide 4.2AA, a mutant lacking the
      cystine, generated no axial defects. We have therefore shown for the first time
      in vivo that the temporally inappropriate presence of SPARC is associated with
      perturbations in tissue morphogenesis. Moreover, we have identified at least one
      bioactive region of SPARC as the C-terminal disulfide-bonded, Ca(2+)-binding loop
      that was previously shown to be both counteradhesive and growth-inhibitory.

PMID- 9154152
TI  - Differential expression of the carbonic anhydrase genes for CA VII (Car7) and CA
      RP VIII (Car8) in mouse brain.
AB  - The spatial expression patterns of the two alpha-carbonic anhydrase genes, CA VII
      and CA-RP VIII (called Car7 and Car8 in the mouse) were examined in the mouse
      brain by in situ hybridization. These two genes are the most highly conserved
      evolutionarily among the mammalian alpha-CAs. Both genes showed a similarly wide
      expression pattern in the brain. In the cerebrum, mRNA expression was detected in
      the pia, choroid plexus, and neurons of the cortical layer, thalamus, and medial
      habenulae. A high level of expression appeared in the pyramidal and granular
      cells of the hippocampus. In the cerebellum, both Car7 and Car8 were transcribed
      to different degrees in the Purkinje cells, and a lower expression level occurred
      in the molecular and granular cell layers. Transcription signals for both genes
      were excluded from the white matter regions.

PMID- 9154153
TI  - Distribution of casein-like proteins in various organs of rat.
AB  - Casein-like proteins were detected in various organs of rat by use of a specific
      antiserum raised against rat milk caseins. The antiserum specifically recognized
      alpha 1-, alpha 2-, beta-, and gamma-caseins in rat milk by Western blot
      analysis, whereas no immunoreactive band was observed in sera of rat and fetal
      bovine and in bovine caseins. Immunohistochemical studies of this antiserum on
      formalin-fixed mammary glands showed that immunoreactive caseins were localized
      to the apical portion of the cytoplasm in lactating mammary epithelial cells and
      in the luminal secretion, which indicates a directional secretion of caseins to
      the lumen by the mammary epithelial cells. With this antiserum, immunoreactive
      substances were detected in various organs, including the pancreatic ducts and
      islets of Langerhans, the secretory ducts of salivary glands, zona fasciculata
      cells and ganglion cells of adrenal gland, distal tubules and convoluted
      collecting tubules of kidney, epithelial cells of bronchioles and large
      pneumocytes of the lung, hair follicles, sebaceous glands, and the prickle cell
      layer of skin, uterine glands and epithelium of the endometrium, hepatic bile
      ducts, and brain. In Western blot analysis, major immunoreactive substances in
      the above organ extracts showed a similarity in molecular weight to alpha 2
      casein of rat milk. Skin was the only tissue that expressed both alpha 2- and
      beta-caseins. There were no other immunoreactive bands with similarity to beta-
      and gamma-caseins in the other organ extracts, but higher molecular weight
      immunoreactive bands (> 100 kD) were detected in some organ extracts, such as
      salivary gland, kidney, liver, lung, and uterus. These findings suggest that the
      alpha 2-casein-like substance is localized not only in the mammary gland but also
      in a variety of organs and may play an important role as a functional molecule in
      those organs.

PMID- 9154154
TI  - Differential staining of apoptotic nuclei in living cells: application to
      macronuclear elimination in Tetrahymena.
AB  - Acridine orange (AO) has been used as a vital fluorescent stain to identify
      apoptotic cells in Drosophila, but little is known about what structures are
      stained. We explored the specificity of AO staining while studying nuclear
      apoptosis in Tetrahymena. Using AO alone or together with the vital nuclear stain
      Hoechst 33342 (HO), we find that lysosomes are generally clustered around the
      degenerating nucleus and that such nuclei are stained an orange-red color, like
      lysosomes. Significantly, the combined dyes, more so than with AO alone,
      distinguish between apoptotic and normal (or necrotic) nuclei by a clear color
      difference. Moreover, these dyes differentially stain apoptotic and normal nuclei
      in avian chondrocytes. The differential staining results are nullified in fixed
      cells or in cytoskeletal preparations treated with RNAse. Similarly,
      lysosomotrophic agents eliminate the differential staining. Our results are
      consistent with acidification of the apoptotic nucleus, possibly by fusion with
      lysosomes. However, even under basic conditions, the macronucleus condenses and
      is eliminated, suggesting that, if the nucleus is becoming acidified,
      acidification by itself is not essential for nuclear elimination. The
      differential staining procedure may provide a useful method for specifically
      identifying apoptotic cells and separating them for further analysis.

PMID- 9154155
TI  - Cellular distribution of branched-chain amino acid aminotransferase isoenzymes
      among rat brain glial cells in culture.
AB  - The first step in the catabolism of branched-chain amino acids (BCAA), reversible
      transamination, is catalyzed by one of the two isoforms of branched-chain amino
      acid aminotransferase (BCAT). The mitochondrial isoenzyme (BCATm) is widely
      distributed among tissues, whereas the cytosolic isoenzyme (BCATc) is restricted
      to only a few organs. Remarkably, BCATc is the prominent isoenzyme found in
      brain. The physiological significance of the subcellular compartmentation of BCAT
      is still not understood. To contribute to the elucidation of the cellular
      distribution of the two isoenzymes in brain, we used cultured rat glial cells in
      an immunocytochemical study to determine the pattern of BCAT isoenzyme expression
      by glial cells. Antiserum against BCATm generated a punctate staining pattern of
      astroglial cells, confirming the mitochondrial location of this isoenzyme. In
      contrast, the cytosol of galactocerebroside-expressing oligodendroglial cells and
      O2A progenitor cells displayed intense staining only for BCATc. In addition,
      subpopulations of astroglial cells exhibited BCATc immunoreactivity. The presence
      of BCATm in astrocytes is consistent with the known ability of these cells to
      oxidize BCAA. Furthermore, our results on BCATc provide support for the
      hypothesis that BCATs are also involved in nitrogen transfer from astrocytes to
      neurons.

PMID- 9154156
TI  - Specificity of antibodies against rodent transforming growth factor-alpha
      protein.
AB  - We found that the immunohistochemical distribution of TGF-alpha varied in rodent
      tissues depending on the antibody used, suggesting that the specificity of anti
      TGF-alpha antibodies differs significantly. To address this issue, we compared
      the specificity of two representative antibodies that have been widely used to
      detect rodent TGF-alpha. In a competition study, the antibodies were preincubated
      with an excess of synthetic rat TGF-alpha 34-50 and were used for staining of rat
      and mouse kidneys and/or uterus. The results revealed that one of the antibodies,
      anti-rat TGF-alpha polyclonal antibody, was neutralized by the peptide, whereas
      the other, anti-human TGF-alpha monoclonal antibody, was not absorbed by the
      peptide up to an excess of 100-fold. Western blotting analysis showed that the
      anti-rat TGF-alpha polyclonal antibody recognized both human and rat purified TGF
      alpha. However, the anti-human TGF-alpha monoclonal antibody did not detect
      purified rat TGF-alpha, although the antibody reacted with mouse proteins other
      than TGF-alpha from kidneys and uterus, purified human TGF-alpha, and mouse
      carbonic anhydrase II. These data indicate that the anti-human TGF-alpha
      monoclonal antibody does not recognize rodent TGF-alpha under our experimental
      conditions and suggest that distribution of TGF-alpha in rodent tissues may need
      to be reexamined.

PMID- 9154158
TI  - Apoptosis and proliferation of fibroblasts during postnatal skin development and
      scleroderma in the tight-skin mouse.
AB  - Tight-skin (Tsk) is a dominant gene mutation that causes a fibrotic skin disease
      in mice, similar to human scleroderma. Both conditions are characterized by
      increased numbers of dermal fibroblasts containing high levels of procollagen
      mRNA. Whether this fibroblast population arises from fibroblast growth or
      fibroblast transcriptional activation is debated. Proliferation and apoptosis of
      fibroblasts of normal and Tsk mice were studied in skin sections before, at
      onset, and in established fibrosis. Tissues sections were immunostained with
      proliferating cell nuclear antigen (PCNA) as proliferation marker. Apoptosis was
      investigated by in situ end-labeling of fragmented DNA and nuclear staining with
      propidium iodide. The expression of the apoptosis inhibitor Bcl-2 was
      investigated by immunohistochemistry. We demonstrate differences in fibroblast
      proliferation and apoptosis related to postnatal skin growth and development.
      Neonatal skin exhibits the highest levels of proliferation and apoptosis in
      fibroblasts. In contrast, low proliferation and absence of apoptosis
      characterizes adult fibroblasts. Skin fibroblasts express Bcl-2 only in newborns,
      and at other ages Bcl-2 was restricted to epithelial cells. Our results also
      suggest that neither increased fibroblast proliferation nor defective apoptosis
      accounts for the fibrotic phenotype of Tsk. Therefore, transcriptional activation
      of extracellular matrix genes appears more relevant in the pathogenesis of Tsk
      fibrosis.

PMID- 9154157
TI  - Tumor collagenase stimulatory factor (TCSF) expression and localization in human
      lung and breast cancers.
AB  - Tumor cell-derived collagenase stimulatory factor (TCSF) stimulates in vitro the
      biosynthesis of various matrix metalloproteinases involved in tumor invasion,
      such as interstitial collagenase, gelatinase A, and stromelysin 1. The expression
      of TCSF mRNAs was studied in vivo, using in situ hybridization and Northern
      blotting analysis, in seven normal tissues and in 22 squamous cell carcinomas of
      the lung, and in seven benign proliferations and in 22 ductal carcinomas of the
      mammary gland. By in situ hybridization, TCSF mRNAs were detected in 40 of 44
      carcinomas, in pre-invasive and invasive cancer cells of both lung and breast
      cancers. TCSF mRNAs and gelatinase A mRNAs were both visualized in the same areas
      in serial sections in breast cancers, and were expressed by different cells,
      tumor cells, and fibroblasts. The histological results were confirmed by Northern
      blot analysis, which showed a higher expression of TCSF mRNAs in cancers than in
      benign and normal tissues. These observations support the hypothesis that TCSF is
      an important factor in lung and breast tumor progression.

PMID- 9154159
TI  - Improved in situ hybridization to HIV with RNA probes derived from PCR products.
AB  - These experiments tested the hypothesis that a pool of PCR-derived RNA probes
      with defined length and even representation of the target sequences could produce
      more specific and intense in situ hybridization signals than randomly size
      reduced, plasmid-derived RNA probes. In situ hybridization was performed with
      sense and anti-sense HIV-1 RNA probes that were derived from PCR products tailed
      with the T7 RNA polymerase promoter or from plasmid DNA. In situ hybridization
      using a pool of seven anti-sense or sense PCR-derived RNA probes (1805
      nucleotides of HIV sequence, 257 nucleotides average probe length) was compared
      with hybridization using anti-sense or sense RNA probes made from a plasmid
      representing the HIV-1 env gene (3151 nucleotides of HIV-1 target). The pooled
      PCR-derived probes resulted in stronger in situ hybridization signals and less
      background than those produced with plasmid-derived RNA probes. This method for
      creating PCR-derived RNA probes improves the feasibility of synthesizing
      multiple, discrete RNA probes for studies of specific mRNA expression because it
      does not require the subcloning steps used to construct plasmids. PCR-derived RNA
      probes may provide a viable alternative to the use of plasmid-derived RNA probes
      for in situ hybridization.

PMID- 9154160
TI  - Sensitive chemiluminescence in situ hybridization for the detection of human
      papillomavirus genomes in biopsy specimens.
AB  - We developed a sensitive chemiluminescence in situ hybridization assay for
      detection of human papillomavirus (HPV) DNA for objective and semiquantitative
      evaluation of the results. The hybridization reaction was performed using either
      digoxigenin-, biotin-, or fluorescein-labeled probes, visualized with alkaline
      phosphatase as the revealing enzyme and a highly sensitive 1,2 dioxetane
      phosphate as chemiluminescent substrate. The light emitted from the hybridized
      probes was detected, analyzed, and measured using a high-performance, low light
      level imaging luminograph connected to an optical microscope and to a personal
      computer for quantification of the photon fluxes and for image analysis. The
      system operated in consecutive steps: First, hybridized specimens were recorded
      in transmitted light. Then the net luminescent signal was recorded, and then an
      overlay of the two images provided by the transmitted light and by the
      luminescent signal allowed the spatial distribution of the target DNA to be
      localized, measured, and evaluated. Biopsy specimens from different pathological
      conditions associated with HPV, which had previously been proved positive for HPV
      DNA with the polymerase chain reaction (PCR), were analysed. The
      chemiluminescence in situ hybridization proved sensitive and specific with
      digoxigenin-, biotin-, or fluorescein-labeled probes, and provided an objective
      evaluation of the results. The results obtained with chemiluminescence in situ
      hybridization were also compared with results obtained with in situ hybridization
      with colorimetric detection, with good concordance of the data. Chemiluminescence
      in situ hybridization therefore offers the possibility of detecting HPV DNA with
      great sensitivity in biopsy specimens. Moreover, the images of the samples,
      stored in the computer, are a permanent record of the reaction and can also be
      sent for evaluation or comparison to other laboratories using computer networks.

PMID- 9154161
TI  - Detection of integrins in formalin-fixed, paraffin-embedded tissues.
AB  - Integrins are heterodimeric transmembrane receptors, which are expressed in many
      cells. In vitro experiments have demonstrated that integrins may be important in
      tumor progression and organ development. The functions of integrins were
      previously studied in cell cultures and their tissue expression was detected by
      immunofluorescence or immunoperoxidase in frozen sections. The purpose of this
      study was to determine the optimal conditions for detection of integrins in
      formalin-fixed, paraffin-embedded tissues. We utilized microwave heating and
      enzyme digestion in routinely processed, surgically removed tissues. Our results
      demonstrate that integrins can be reliably detected in archival material. This
      approach will facilitate further investigation of the role played by integrins in
      human malignancies and in developmental processes.

PMID- 9154162
TI  - A novel technique for mapping the lipid composition of atherosclerotic fatty
      streaks by en face fluorescence microscopy.
AB  - We introduce here a new fluorescence microscopy technique for en face analysis of
      the atherosclerotic fatty streaks (FS). This technique is semiquantitative and
      has the sensitivity and resolution to map lipids to individual cells in FS less
      than 100 microns in diameter. New Zealand White rabbits were fed an atherogenic
      diet for up to 26 weeks. Aortas were fixed in formalin and stained en bloc with
      the fluorescent dyes Nile red and filipin. Fluorescent staining was validated by
      correlating microfluorimetric and biochemical measurements of the lipid content
      in FS. To determine the cell types associated with the different staining
      patterns, FS were also evaluated by transmission electron microscopy (TEM) and
      immunohistochemistry (IH). Correlation of microfluorimetry, TEM, IH, and
      biochemical data indicated that regions rich in non-esterified cholesterol
      stained with filipin and fluoresced blue owing to accumulations of lipid vesicles
      and/or cholesterol crystals. Regions rich in neutral and polar lipids stained
      with Nile red and fluoresced yellow or orange, respectively, owing to
      accumulations of lipids in both macrophages and smooth muscle cells (SMC).
      Digital overlays of the filipin and Nile red images revealed that larger lesions
      (> 0.5 mm diameter) had a "nested" distribution of lipids, with a blue (filipin)
      fringe surrounding an orange (Nile red) fringe surrounding a yellow (Nile red)
      center.

PMID- 9154164
TI  - 4th International Symposium on Myelodysplastic Syndromes. Barcelona, Spain, 24-27
      April 1997. Abstracts.

PMID- 9154163
TI  - Dde-I restriction endonuclease fragmentation: a novel method of generating cDNA
      probes for in situ hybridization in brain.
AB  - We present a novel procedure for detection of low- and high-abundance messenger
      RNAs in the brain by in situ hybridization histochemistry, by using fragmented
      double-stranded cDNA as molecular probes. The procedure involves digesting the
      cDNA of interest with the restriction endonuclease from Desulfocibrio
      desulfuricans (Dde I digestion), followed by random primed labeling, which
      generates a family of high specific activity cDNA fragments. This procedure is a
      rapid, straightforward, and reproducible method of obtaining sensitive probes for
      in situ hybridization and is generally applicable to the analysis of the
      expression of a large number of genes. Here we report the use of this procedure
      to prepare probes for the detection of synapsin I, p150Glued, neurotensin, c-fos,
      and c-jun mRNAs in brain, using both isotopic and non-isotopic labeling methods.
      Because this procedure does not require complex recombinant DNA manipulations or
      oligonucleotide design, it should prove useful to the non-molecular biologist
      examining the expression of genes in the central nervous system.

PMID- 9154166
TI  - New agents for cancer chemoprevention.
AB  - Clinical chemoprevention trials of more than 30 agents and agent combinations are
      now in progress or being planned. The most advanced agents are well known and are
      in large Phase III chemoprevention intervention trials or epidemiological
      studies. These drugs include several retinoids [e.g., retinol, retinyl palmitate,
      all-trans-retinoic acid, and 13-cis-retinoic acid], calcium, Beta carotene,
      vitamin E, tamoxifen, and finasteride. Other newer agents are currently being
      evaluated in or being considered for Phase II and early Phase III chemoprevention
      trials. Prominent in this group are all-trans-N-(4-hydroxy phenyl)retinamide (4
      HPR) (alone and in combination with tamoxifen), 2-difluoromethylornithine (DFMO),
      nonsteroidal antiinflammatory drugs (aspirin, piroxicam, sulindac), oltipraz, and
      dehydroepiandrostenedione (DHEA). A third group is new agents showing
      chemopreventive activity in animal models, epidemiological studies, or in pilot
      clinical intervention studies. They are now in preclinical toxicology testing or
      Phase I safety and pharmacokinetics trials preparatory to chemoprevention
      efficacy trials. These agents include S-allyl-l-cysteine, curcumin, DHEA analog
      8354 (fluasterone), genistein, ibuprofen, indole-3-carbinol, perillyl alcohol,
      phenethyl isothiocyanate, 9-cis-retinoic acid, sulindac sulfone, tea extracts,
      ursodiol, vitamin D analogs, and p-xylyl selenocyanate. A new generation of
      agents and agent combinations will soon enter clinical chemoprevention studies
      based primarily on promising chemopreventive activity in animal models and in
      mechanistic studies. Among these agents are more efficacious analogs of known
      chemopreventive drugs including novel carotenoids (e.g., alpha-carotene and
      lutein). Also included are safer analogs which retain the chemopreventive
      efficacy of the parent drug such as vitamin D3 analogs. Other agents of high
      interest are aromatase inhibitors (e.g., (+)-vorozole), and protease inhibitors
      (e.g., Bowman-Birk soybean trypsin inhibitor). Combinations are also being
      considered, such as vitamin E with l-selenomethionine. Analysis of signal
      transduction pathways is beginning to yield classes of potentially active and
      selective chemopreventive drugs. Examples are ras isoprenylation and epidermal
      growth factor receptor inhibitors.

PMID- 9154165
TI  - A purinergic hypothesis for immunomodulation.

PMID- 9154167
TI  - Use of in vitro assays to predict the efficacy of chemopreventive agents in whole
      animals.
AB  - Five in vitro assays have been applied to screen the efficacy of potential
      chemopreventive agents. These assays measure a) inhibition of morphological
      transformation in rat tracheal epithelial (RTE) cells, b) inhibition of anchorage
      independence in human lung tumor (A427) cells, c) inhibition of hyperplastic
      alveolar nodule formation in mouse mammary organ cultures (MMOC), d) inhibition
      of anchorage independence in mouse JB6 epidermal cells, and e) the inhibition of
      calcium tolerance in human foreskin epithelial cells. The efficacy of many of
      these same agents in whole animal studies of lung, colon, mammary gland, skin,
      and urinary bladder carcinogenesis has also been measured. The aim herein is to
      estimate the positive and negative predictive values of these in vitro assays
      against whole animal chemopreventive efficacy data using the same chemicals. For
      three of these assays--using RTE, A427 cells and mouse mammary organ culture
      (MMOC)-enough data are available to allow the estimate to be made. Such
      extrapolations of in vitro data to the in vivo situation are difficult at best.
      There are many dissimilarities between the two assay systems. The in vitro assays
      use respiratory and mammary epithelial cells, while the in vivo assays use
      respiratory, mammary, colon, bladder and skin cells. The in vitro assays use the
      carcinogens benzo(a)pyrene (B(a)P) and 7,12-dimethylbenz(a)anthracene (DMBA),
      while the in vivo assays use B(a)P, DMBA, N-methyl-N-nitrosourea (MNU), N,N'
      diethylnitrosamine (DEN), azoxymethane (AOM), and N-butyl-N-(4
      hydroxybutyl)nitrosoamine (OH-BBN). There are vast differences in
      pharmacodynamics and pharmacokinetics in vitro and in vivo, yet it is possible to
      rapidly screen chemicals in vitro for efficacy at one-tenth the cost and complete
      tests in weeks instead of months. A positive in vitro assay was defined as a 20%
      inhibition (compared with control) for the RTE and A427 assays and a 60%
      inhibition for the MMOC assay at nontoxic concentrations. For in vivo assays, the
      criterion for a positive result was a statistically significant inhibition of
      incidence, multiplicity or a significant increase in latency (mean time to first
      tumor). For an agent to be considered negative in animals, it required negative
      results in at least two different organ systems and no positive results. Using
      the battery of three in vitro tests, the positive predictive value for having
      one, two, or three positive in vitro assays and at least one positive whole
      animal test was 76%, 80%, and 83% respectively. The negative predictive values
      for one, two or all three in vitro assays was 25%, 27%, and 50%. From these data
      it is observed that in vitro assays give valuable positive predictive values and
      less valuable negative predictive values. The mechanisms of chemoprevention are
      not well understood. Seven categories of agents were examined for their cancer
      preventing both in vitro and in vivo: antiinflammatories, antioxidants,
      arachadonic acid metabolism inhibitors, GSH inducers, GST inducers, ODC
      inhibitors, and PKC inhibitors. Three or even five in vitro assays cannot be all
      inclusive of the many mechanisms of cancer prevention. However, three assays help
      to predict whole animal efficacy with reasonable positive predictive values. Much
      work and development remains to be done to rapidly identify new chemopreventive
      drugs.

PMID- 9154168
TI  - Strategy and planning for chemopreventive drug development: clinical development
      plans II.
AB  - This is the second publication of Clinical Development Plans from the National
      Cancer Institute, Division of Cancer Prevention and Control, Chemoprevention
      Branch and Agent Development Committee. The Clinical Development Plans summarize
      the status of promising chemopreventive agents regarding evidence for safety and
      chemopreventive efficacy in preclinical and clinical studies. They also contain
      the strategy for further development of these drugs, addressing pharmacodynamics,
      drug effect measurements, intermediate biomarkers for monitoring efficacy,
      toxicity, supply and formulation, regulatory approval, and proposed clinical
      trials. Sixteen new Clinical Development Plans are presented here: curcumin,
      dehydroepiandrosterone, folic acid, genistein, indole-3-carbinol, perillyl
      alcohol, phenethyl isothiocyanate, 9-cis-retinoic acid, 13-cis-retinoic acid, l
      selenomethionine and 1, 4-phenylenebis(methylene)selenocyanate, sulindac sulfone,
      tea, ursodiol, vitamin A, and (+)-vorozole. The objective of publishing these
      plans is to stimulate interest and thinking among the scientific community on the
      prospects for developing these and future generations of chemopreventive drugs.

PMID- 9154169
TI  - Clinical development plan: curcumin.

PMID- 9154170
TI  - Clinical development plan: dehydroepiandrosterone (DHEA).

PMID- 9154171
TI  - Clinical development plan: folic acid.

PMID- 9154172
TI  - Clinical development plan: genistein.

PMID- 9154173
TI  - Clinical development plan: indole-3-carbinol.

PMID- 9154174
TI  - Clinical development plan: l-perillyl alcohol.

PMID- 9154175
TI  - Clinical development plan: phenethyl isothiocyanate.

PMID- 9154176
TI  - Clinical development plan: 9-cis-retinoic acid.

PMID- 9154177
TI  - Clinical development plan: 13-cis-retinoic acid.

PMID- 9154178
TI  - Clinical development plan: l-Selenomethionine.

PMID- 9154179
TI  - Clinical development plan: 1,4-penylenebis(methylene)selenocyanate.

PMID- 9154180
TI  - Clinical development plan: sulindac sulfone.

PMID- 9154181
TI  - Clinical development plan: tea extracts. Green tea polyphenols. Epigallocatechin
      gallate.

PMID- 9154182
TI  - Clinical development plan: ursodiol.

PMID- 9154183
TI  - Clinical development plan: vitamin A.

PMID- 9154184
TI  - Clinical development plan: (+)-vorozole.

PMID- 9154185
TI  - Hepatitis A infrequent food link, but of concern...

PMID- 9154186
TI  - Cooperation key to handling feral cat population.

PMID- 9154187
TI  - In support of animal rights dialogue.

PMID- 9154188
TI  - Comments on greyhounds with cutaneous and renal vasculopathy.

PMID- 9154189
TI  - Comments on greyhounds with cutaneous and renal vasculopathy.

PMID- 9154190
TI  - Drugs and biologics are not a substitute for effective management by food animal
      veterinarians.

PMID- 9154191
TI  - What is your diagnosis? Chronic sepsis of the distal interphalangeal joint and
      distal portion of the sesamoid bursa.

PMID- 9154192
TI  - Interstitial cell tumor.

PMID- 9154193
TI  - Veterinary student wins DHHS secretary's certificate of merit in innovations in
      health promotion and disease prevention writing competition.

PMID- 9154194
TI  - An overview of the pathogenesis of canine hip dysplasia.
AB  - Canine hip dysplasia (CHD) is an inherited, developmental condition that involves
      a lack of conformity between the femoral head and acetabulum and invariably leads
      to osteoarthritis. In this paper, the author briefly reviews what is known about
      the genetics of CHD, how joint laxity and growth rate are related to development
      of CHD, and the possibility that CHD is a systemic disease involving multiple
      joints, not just the hip joint.

PMID- 9154195
TI  - Pathologic alterations in canine hip dysplasia.
AB  - The pathologic changes in articular cartilage appear to be of central importance
      in the development of canine hip dysplasia. But, articular cartilage has only a
      limited number of responses to injury and a limited capacity for repair. Damage
      to articular cartilage in dogs with canine hip dysplasia is likely multifactorial
      in origin, involving cytokines, abnormal load-bearing, and, possibly, other
      undefined factors.

PMID- 9154196
TI  - Advances in diagnosing canine hip dysplasia.
AB  - The DI method was developed, at least in part, because of perceived variations
      among radiologists in regard to subjective hip scores assigned to radiographs. It
      also was recognized that the prevalence of CHD among many dog breeds was
      disturbingly high, despite efforts to lower the prevalence using subjective score
      as a selection criterion. The DI method was developed on the basis of results of
      mechanical testing of cadaver hip joints, which accomplished 3 principal
      objectives. First, it showed that when the hip joint is in the standard, hip
      extended, internally rotated position, passive laxity is minimized. Second, it
      showed that passive laxity was maximized when the hip joint is in the neutral
      position. Third, it demonstrated the sigmoidal nature of the load/displacement
      curve for the hip joint in the neutral position, which suggested that high
      repeatability from examiner to examiner in regard to DI could be expected without
      the need to standardize applied force. The mean and range of DI were shown to
      vary from 1 breed to the next, but within an individual dog, DI appears to remain
      constant (within limits of scientific acceptability and clinical applicability)
      from 16 weeks of age. Passive hip laxity measured on the distraction view is, on
      average, 2.5 to 11 times greater than that measured on the standard, hip-extended
      radiographic view. Performance Borzois and Greyhounds, which have an extremely
      low prevalence of CHD, uniformly have tight hip joints (DI < 0.3), and mean DI
      for dog breeds that have a high prevalence of CHD is significantly greater than
      mean DI for Borzois and Greyhounds. However, individual dogs that have DI < 0.3,
      even though members of breeds prone to CHD, have a low risk of developing DJD.
      Some, but not all, dogs with DI > 0.3 will develop DJD by 3 years of age, and DI
      has been shown to be the principal risk factor for development of DJD.
      Susceptibility to development of DJD appears to be breed-specific. For example,
      given equivalent DI, German Shepherd Dogs are more at risk for developing DJD
      than are Rottweilers. Heritability of DI is higher than that of the subjective
      hip score; thus, selection pressure based on DI should result in faster genetic
      change than selection pressure based on subjective hip scores. Finally, the DI
      method has been performed on approximately 14,000 dogs, some of which were
      evaluated multiple times. It is apparent that this method is no more harmful than
      the standard, hip-extended radiographic method or palpation performed as part of
      a routine orthopedic examination.

PMID- 9154197
TI  - Onset of epiphyseal mineralization and growth plate closure in radiographically
      normal and dysplastic Labrador retrievers.
AB  - OBJECTIVE: To determine whether onset of mineralization of the femoral and
      proximal tibial epiphyses and age at closure of the femoral and acetabular
      triradiate growth plates was different for Labrador Retrievers that were
      radiographically normal or that had canine hip dysplasia (CHD). DESIGN: Cohort
      study. ANIMALS: 36 Labrador Retriever puppies. PROCEDURE: Puppies were
      radiographed every other day from the time they were 8 to 10 days old until
      ossification of the femoral heads was apparent. Radiographs were then obtained
      weekly until puppies were 1 month old and then monthly until puppies were 8 to 12
      months old. Age at which mineralization was first observed in the proximal and
      distal femoral and proximal tibial epiphyses and at which the femoral capital,
      triradiate acetabular, and distal femoral growth plates were no longer
      radiographically visible were recorded. Fifteen dogs were euthanatized and
      necropsied to determine whether dogs had CHD. RESULTS: There were 26
      radiographically normal left and right hip joints and 10 dysplastic left and
      right hip joints. Onset of mineralization of the proximal femoral epiphyses and
      of the right proximal tibial epiphysis was significantly later in dysplastic than
      in radiographically normal puppies. The left femoral capital growth plates closed
      significantly later in dysplastic than in radiographically normal joints, but
      other differences in growth plate closure were not detected. CLINICAL
      IMPLICATIONS: Endochondral ossification may be abnormal in dogs with CHD. The
      disease appears to affect multiple joints, even though it is most evident
      clinically in the hip joint.

PMID- 9154198
TI  - The joint capsule and joint laxity in dogs with hip dysplasia.
AB  - Present knowledge of the complexity of joint diseases makes it difficult to
      investigate the causes and early pathogenesis of canine hip dysplasia. Clinical
      signs of canine hip dysplasia including joint laxity may be a result of primary
      or secondary alterations of the joint. We already know that joint laxity is
      related to effusive synovitis (ie, accumulation of synovial fluid) and to other
      primary collagenous diseases. Canine hip dysplasia may be a third collagenous
      disease associated with joint laxity. This paper summarizes some of the studies
      that investigated the relationship between joint laxity and a defect in collagen
      metabolism and the influence that alterations in transsynovial flow have on joint
      laxity.

PMID- 9154199
TI  - Association between pelvic muscle mass and canine hip dysplasia.
AB  - OBJECTIVE: To investigate the relationship between pelvic muscle mass and
      development and expression of canine hip dysplasia (CHD). DESIGN: Prospective
      study. ANIMALS: 5 Greyhounds with anatomically normal hip joints, 59 German
      Shepherd Dogs (23 with CHD, 24 with near-normal hip joints, and 12 with normal
      hip joints), and 18 German Shepherd Dog-Greyhound crossbreeds (7 with CHD, 6 with
      near-normal hip joints, and 5 with normal hip joints) between 12 and 47 months
      old in which pelvic muscle mass was evaluated. Pectineal muscle and hip joint
      development were evaluated in 25 German Shepherd Dogs at 8 and 16 or 24 weeks of
      age. PROCEDURES: For evaluation of pelvic muscle mass, individual pelvic muscles
      were weighed and hip joints were assigned a score on the basis of severity of
      degenerative changes. For evaluation of pectineal muscle development, muscle
      sections were stained and examined. RESULTS: Pelvic muscle mass was greatest in
      Greyhounds, intermediate in crossbred dogs, and smallest in German Shepherd Dogs.
      Differences in pelvic muscle mass among breeds were attributable to differences
      in weights of individual muscles. Hip score was negatively correlated with pelvic
      muscle mass and weights of selected pelvic muscles. Dogs with pectineal
      hypotrophy at 8 weeks of age had type-2 muscle fiber paucity or muscle fiber-type
      grouping at 16 or 24 weeks of age. At 8 weeks of age, hip joints were composed of
      multiple centers of ossification, and the acetabulum was largely cartilaginous.
      By 24 weeks of age, the pelvic bones were largely, although incompletely, fused.
      CLINICAL IMPLICATIONS: Diminished pelvic muscle mass in dogs with CHD and altered
      muscle fiber size and composition in 8-week-old dogs that subsequently develop
      CHD strongly suggest that abnormalities of pelvic musculature are associated with
      development of CHD. The complex development of the hip joint from multiple
      centers of ossification may make the joint susceptible to abnormal modeling
      forces that would result from abnormalities in pelvic muscle mass.

PMID- 9154200
TI  - Genetics of canine hip dysplasia.
AB  - OBJECTIVE: To document genetic progress in improving hip quality of dogs
      maintained in a closed breeding colony to produce dogs for training as guides for
      blind people. DESIGN: Prospective analysis of hip quality records from a breeding
      trial that encompassed 3 full generations and included some dogs born into the
      fourth and fifth generations. ANIMALS: Hip quality was assessed for 2,037 German
      Shepherd Dogs and 1,821 Labrador Retrievers from 1980 to 1996. PROCEDURE: A
      subjective hip score assigned by 1 radiologist was used to assess hip quality
      during the study period. In the past 8 years, the distraction index was also
      used. Genetic change was produced by selecting a small percentage of dogs to be
      parents of the next generation. Dogs were selected to become parents of the next
      generation on the basis of estimated breeding values. These were calculated by
      combining observed values of individual dogs with known relationships in the
      population pedigrees to predict which dogs were the best candidates for selection
      as parents. RESULTS: In < 5 generations of selection, the percentage of German
      Shepherd Dogs with canine hip dysplasia at 12 to 16 months of age decreased from
      55 to 24%. Among Labrador Retrievers, the percentage decreased from 30 to 10%.
      CLINICAL IMPLICATIONS: This report gives practitioners documented proof that
      genetic selection will work to improve hip quality. Dog breeders must be advised
      to be patient, however, to allow enough generations to elapse to make meaningful
      genetic change.

PMID- 9154201
TI  - A review of the progress in canine hip dysplasia control in Britain.
AB  - Results of the British Veterinary Association/Kennel Club program for controlling
      canine hip dysplasia (CHD) were reviewed for 6 breeds to determine whether there
      had been any progress in reducing the prevalence of CHD. Although there was a
      decrease in mean hip dysplasia score for some of the 6 breeds when results for
      the 1991 to 1995 period were compared with those for 1987 to 1990, there were not
      any consistent trends in 5 of the breeds, and there was a clear worsening of the
      mean hip score in Siberian Huskies. In general terms, not only has there been a
      steady increase in the percentage of parents that were scored or, more
      accurately, an increase in the use of scored parents when breeding, but in broad
      terms the weighted mean score for the parents was lower (ie, better) than the
      mean score for all dogs in the breed during each period. In all breeds, there
      appeared to have been some selection to reduce total hip score, but in all but 1
      instance, the expected result was not achieved, with actual values being higher
      (ie, worse) than those expected from theory. If the incidence of CHD is to
      diminish in Britain, then, as a first step, the Kennel Club must insist that, in
      affected breeds, only progeny of scored parents may be registered. Thereafter, a
      gradual tightening of the parental scores that will be accepted in each breed
      should be attempted, and best linear unbiased predictor-type indices should be
      established and applied to sires and dams to ensure wider usage of the better
      parents.

PMID- 9154202
TI  - Variations in composition of cartilage from the shoulder joints of young adult
      dogs at risk for developing canine hip dysplasia.
AB  - OBJECTIVE: To determine whether the composition of cartilage from the shoulder
      joints of dogs varied with the risk of developing canine hip dysplasia (CHD).
      DESIGN: Observational study. ANIMALS: 12 skeletally mature (approx 1 year old)
      Labrador Retrievers. PROCEDURE: Dogs were classified as having a low, moderate,
      or high risk of developing CHD on the basis of distraction indices. Cartilage was
      harvested from the craniolateral and weight-bearing regions of the humeral heads,
      and wet weight per unit area and dry, glycosaminoglycan, and fibronectin contents
      were determined. RESULTS: Glycosaminoglycan and dry contents did not vary among
      risk groups. For cartilage from the craniolateral region of the humeral head, wet
      weight per unit area and fibronectin content increased as risk of developing CHD
      increased. Wet weight and fibronectin content of cartilage from the weight
      bearing region of the humeral head did not vary among risk groups. CLINICAL
      IMPLICATIONS: Dogs that have a high risk of developing CHD are also more likely
      to develop osteoarthritis of the shoulder joint. The observed increases in wet
      weight per unit area and fibronectin content in cartilage from the craniolateral
      region of the humeral head in dogs at a high risk of developing CHD may be early
      sings of incipient osteoarthritis.

PMID- 9154203
TI  - Mechanisms of action of anti-inflammatory medications used for the treatment of
      osteoarthritis.
AB  - Nonsteroidal anti-inflammatory (NSAID) drugs have been used to treat
      osteoarthritis ever since 1899, when the effects of aspirin were first
      recognized. Widespread use of these compounds continues despite their recognized
      potential toxicity, mostly because they are generally effective for palliation of
      the pain associated with osteoarthritis. The discovery of cyclooxygenase (COX)-1
      and COX-2 has sparked interest in development of NSAID that specifically target
      COX-2, with the hope that such compounds would be associated with a lower
      incidence of adverse gastrointestinal effects. Other potential methods of
      avoiding adverse gastrointestinal effects associated with NSAID use include
      concurrent administration of prostaglandins and use of pure analgesics, such as
      acetaminophen. The role of nitric oxide in inflammation is an exciting area of
      research, and addition of nitric oxide-producing moieties to NSAID may prove to
      be another mechanism of avoiding gastrointestinal toxicity. There is likely to be
      considerable reward for the development of an NSAID that relieves pain associated
      with a wide variety of conditions, does not cause gastrointestinal toxicoses, and
      spares normal cartilage. Whether such a drug exists remains speculative.

PMID- 9154204
TI  - Use of carprofen for the treatment of pain and inflammation in dogs.
AB  - Most studies of nonsteroidal anti-inflammatory drugs (NSAID) do not demonstrate
      appreciable differences in efficacy. As awareness of the adverse effects
      associated with NSAID use increases, safety is becoming the primary concern among
      physicians when selecting NSAID for use by their human patients. However,
      veterinarians may be less aware of the safety concerns associated with NSAID use.
      A wide range of NSAID is used to treat human beings with osteoarthrits; however,
      it is imperative to remember that dogs are especially sensitive to these drugs,
      and reports of serious, and occasionally fatal, complications are numerous.
      Carprofen is a propionic acid-derived NSAID that has anti-inflammatory,
      analgesic, and antipyretic activity. In animals, carprofen is as potent as
      indomethacina and more potent than aspirin or phenlbutazone, but carprofen
      appears to be safer than most other NSAID.

PMID- 9154205
TI  - Association between management practices, dairy herd characteristics, and somatic
      cell count of bulk tank milk.
AB  - OBJECTIVE: To determine whether particular dairy management practices and herd
      characteristics were associated with somatic cell count (SCC) of bulk tank milk.
      DESIGN: Analysis of records. SAMPLE POPULATION: Milk samples collected from
      59,435 cows housed in 843 dairy herds between March 1992 and June 1994.
      PROCEDURE: Results of bacterial culture of milk samples and data on farm housing,
      sanitation, milking system, and management were collected. Multiple regression
      analysis was used to determine sources of variation in bulk tank milk SCC among
      herds. RESULTS: Prevalence of Streptococcus agalactiae and Staphylococcus aureus
      mastitis was associated with bulk tank milk SCC. In herds free of S agalactiae
      mastitis, prevalence of S aureus and Corynebacterium bovis mastitis were
      important. For herds without S agalactiae mastitis, use of sawdust bedding was
      associated with a decrease in SCC and a dirty loose housing area was associated
      with an increase. Increased milk production, repeated mastitis control visits,
      and use of particular predip compounds were significantly associated with reduced
      SCC in all herds, regardless of whether any cows in the herd had S agalactiae
      mastitis. In herds with S agalactiae mastitis, use of iodine (certain
      concentrations), chlorhexidine, peroxide, or sodium chlorite-lactic acid as a
      predip was associated with a decrease in SCC. Only use of sodium chlorite-lactic
      acid predip was significantly associated with a decrease in SCC in herds without
      S agalactiae mastitis. CLINICAL IMPLICATIONS: Important factors associated with
      bulk tank milk SCC were prevalence of S agalactiae and S aureus mastitis, careful
      application of particular predip compounds, avoiding a dirty loose housing area,
      and use of a service to regularly monitor prevalence of mastitis in the herd.

PMID- 9154206
TI  - X-chromosome monosomy in an infertile female llama.
AB  - A 3-year-old female llama was examined because of a history of infertility and
      apparent anovulation. The llama had indifferent behavior when penned with a male,
      but eventually would assume sternal recumbency for breeding. On examination, the
      llama was underweight and small in stature. The uterine horns and ovaries could
      not be identified during palpation or ultrasonography per rectum, and the cervix
      was dilated when examined with a speculum. Chromosomal preparations of
      lymphocytes and skin fibroblasts were performed; all cells examined had a 73, X
      karyotype (X-chromosome monosomy). To our knowledge, this is the first report of
      a chromosomal anomaly in a llama. Signs seen in this llama were similar to those
      seen in mares with X-chromosome monosomy. This condition should be considered in
      the differential diagnosis of infertility in llamas that fail to ovulate,
      especially if other abnormalities such as indifferent sexual behavior and short
      stature are present.

PMID- 9154207
TI  - Molecular psychiatry: does a new field need to examine strategy?

PMID- 9154208
TI  - D3 receptor binding in human brain during cocaine overdose.

PMID- 9154209
TI  - Are neuroadaptations in D3 dopamine receptors linked to the development of
      cocaine dependence?

PMID- 9154210
TI  - Functional consequences of divergence and convergence in physiological signaling
      pathways.

PMID- 9154212
TI  - Meeting report--is there a neurobiology of love?

PMID- 9154211
TI  - Ribosomal RNA: a vehicle for small functional RNAs.

PMID- 9154213
TI  - Where does alcohol act in the brain?

PMID- 9154214
TI  - Does Alzheimer's disease start early in life?
AB  - Aging and Alzheimer's disease are two of the keynotes of our time. Since its
      first description by Aloys Alzheimer about 90 years ago, this neurodegenerative
      condition has advanced to become the fourth most common cause of death in the
      elderly, and is found in more than half of the very elderly demented. Despite new
      findings which are linked to several aspects of Alzheimer's disease, relatively
      little progress has been made toward the discovery of reliable methods for early
      diagnosis or the development of a successful therapy for this debilitating
      disease. It is therefore helpful to recall the major underlying questions related
      to our understanding of the pathogenesis of Alzheimer's disease. This article
      deals with two of these: What is the earliest stage at which we can diagnose the
      disease? What influences the onset and progression of the disease? As simple as
      these questions appear to be, attempts at answering them show us the complicated,
      multi-facetted face of Alzheimer's disease.

PMID- 9154215
TI  - Genetically engineered neural transmission.
AB  - Neural transmission is a communication between neurons and target cells,
      resulting in behavioral and physiological changes. Defective or altered neural
      transmission is thought to occur in neuropsychiatric and neurodegenerative
      illnesses. To probe the biological consequences of defective or altered neural
      transmission, various genetically engineered transgenic mouse models have been
      developed, together with conventional pharmacological manipulation. Via genetic
      manipulation, we are able to engineer specific neurotransmitters, receptors,
      inactivation of neurotransmitters or neural innervation density. Moreover,
      recently developed molecular genetic techniques make it possible to induce either
      a gene knock out event or transgene expression at a discrete time point in a
      specific neuronal population in both embryos and adult animals. In conjunction
      with pharmacological manipulation, these sophisticated genetic manipulations of
      neural transmission will provide new tools to control neural transmission in both
      normal and pathophysiological conditions.

PMID- 9154216
TI  - Differential sensitivity of c-Fos expression in hippocampus and other brain
      regions to moderate and low doses of alcohol.
AB  - Alcohol consumption in humans is characterized by a wide range of behavioral
      effects and pathological consequences that suggest several neuroanatomical
      targets for this drug. To identify these targets we have mapped alcohol-induced
      changes in the expression of the c-Fos protein in the rat brain. Administration
      of a moderate dose of alcohol (1.5 g kg-1) led to a suppression of basal and
      novel environment-induced c-Fos expression in the hippocampus and simultaneous
      induction of this protein in regions important for the reinforcing as well as
      aversive properties of drugs. These include the extended amygdala (including the
      central nucleus of amygdala, bed nucleus of stria terminals and nucleus
      accumbens), regions processing sensory information (including the Edinger
      Westphal nucleus and the paraventricular nucleus of the thalamus) and in stress
      related areas (including the paraventricular nucleus of the hypothalamus, nucleus
      of the solitary tract and several neocortical areas). Repeated administration of
      the same dose of alcohol did not decrease alcohol-mediated suppression of c-Fos
      in the hippocampus, but decreased alcohol-induced expression of c-Fos in other
      areas. A lower dose of acute alcohol (0.5 g kg-1) reduced basal c-Fos expression
      in several areas of the neocortex, hippocampus and hypothalamus. However, while
      this low dose of alcohol was unable to counteract the environmental novelty
      induced c-Fos expression in these areas, it increased c-Fos expression in the
      central nucleus of amygdala (an effect similar to the one observed previously for
      diazepam). Our data suggest that the effects of low doses of alcohol may be due
      to selective GABA-like effects of ethanol, whereas higher doses of ethanol
      involve effects on multiple neurotransmitter systems.

PMID- 9154217
TI  - Studies of the potential role of the dopamine D1 receptor gene in addictive
      behaviors.
AB  - Abnormalities in the dopaminergic reward pathways have frequently been implicated
      in substance abuse and addictive behaviors. Recent studies by Self and coworkers
      have suggested an important interaction between the dopamine D1 and D2 receptors
      in cocaine abuse. To test the hypothesis that the DRD1 gene might play a role in
      addictive behaviors we examined the alleles of the Dde I polymorphism in three
      independent groups of subjects with varying types of compulsive, addictive
      behaviors-Tourette syndrome probands, smokers and pathological gamblers. In all
      three groups there was a significant in the frequency of homozygosity for the
      DRD1 Dde I 1 or 2 alleles in subjects with addictive behaviors. The DRD1 11 or 22
      genotype was present in 41.3% of 63 controls and 57.3% of 227 TS probands (P =
      0.024). When 23 quantitative traits were examined by ANOVA those carrying the 11
      genotype consistently had the highest scores. Based on these results, we examined
      the prevalence of the 11 genotype in controls, TS probands without a specific
      behavior, and TS probands with a specific behavior. There was a progressive,
      linear increase, significant at alpha < or = 0.005 for scores for gambling,
      alcohol use and compulsive shopping. Problems with three additional behaviors,
      drug use, compulsive eating and smoking were significant at alpha < or = 0.05.
      All six variables were related to addictive behaviors. In a totally separate
      group of controls and individuals attending a smoking cessation clinic, and
      smoking at least one pack per day, 39.3% of the controls versus 66.1% of the
      smokers carried the 11 or 22 genotype (P = 0.0002). In a third independent group
      of pathological gamblers, 55.8% carried the 11 or 22 genotype (P = 0.009 vs the
      combined controls). In the TS group and smokers there was a significant additive
      effect of the DRD1 and DRD2 genes. The results for both the DRD1 and DRD2 genes,
      which have opposing effects on cyclic AMP, were consistent with negative and
      positive heterosis, respectively. These results support a role for genetic
      variants of the DRD1 gene in some addictive behaviors, and an interaction of
      genetic variants at the DRD1 and DRD2 genes.

PMID- 9154218
TI  - Abnormal expression of serotonin transporter mRNA in the frontal and temporal
      cortex of schizophrenics.
AB  - Postmortem brain tissue was used to measure expression of serotonin transporter
      mRNA in the left frontal and left temporal cortex from schizophrenics (n = 24)
      and from normal control individuals with no history of psychiatric illness (n =
      10). There was an approximately four-fold increase of serotonin transporter mRNA
      in Brodmann's area 9 and a two-fold decrease in Brodmann's areas 21 and 22. The
      changes in serotonin transporter mRNA were more prominent in schizophrenics who
      had received neuroleptic drugs within 1 week prior to death than in
      schizophrenics who were neuroleptic-free for more than 2 weeks prior to death,
      suggesting that the changes may be related to neuroleptic treatment. There was no
      correlation between serotonin transporter mRNA levels and the sex or age of
      schizophrenic and control cases or the postmortem delay intervals. These results
      support the hypothesis that region-specific changes in serotonin transporter
      expression occur in brains of some schizophrenics. Future studies are necessary
      to determine whether the changes in serotonin transporter expression are drug
      related or are associated with the illness itself.

PMID- 9154219
TI  - NCAM and schizophrenia: genetic studies.
AB  - The hypothesis of a neurodevelopmental dysfunction being involved in the etiology
      of schizophrenia is suggested by the observation of morphological alterations in
      the brains of schizophrenia patients. These alterations may be caused by defects
      in neural cell differentiation or migration, which could lead to disrupted
      neuronal circuitry and to the schizophrenia symptomatology. The neural cell
      adhesion molecule (NCAM) plays a major role in cell migration and axon outgrowth,
      and is involved in synaptic plasticity mechanisms implicated in adult cognitive
      functions. Altered levels of the NCAM polysialylated form, PSA-NCAM, in the brain
      of schizophrenia patients have been reported, and are supportive of a role for
      this molecule in the disorder. To investigate the possible involvement of the
      NCAM gene in schizophrenia, we conducted a comprehensive genetic study, which
      included linkage analysis and an association study employing the Haplotype
      Relative Risk (HRR) design in nuclear families. Our results indicate that
      structural alterations in the NCAM gene are unlikely to play a major role in
      schizophrenia, although a function for the NCAM molecule in the etiology of the
      disease remains an intriguing hypothesis.

PMID- 9154220
TI  - Novel modalities for appraising individual and coordinate pulsatile hormone
      secretion: the paradigm of luteinizing hormone and testosterone release in the
      aging male.
AB  - To quantify aging- and disease-associated alterations in the integrative and
      interactive components of a pulsatile neuroendocrine axis, novel biomathematical
      strategies are required. Here, I illustrate as an investigative paradigm
      otherwise subtle aging-dependent disturbances of the gonadotropin-releasing
      hormone (GnRH)-luteinizing hormone (LH)-testosterone feedback axis in men, in
      whom strong age-related contrasts become evident via any of four strategies
      applied alone or in combination: (1) intensified blood sampling schedules to
      capture the temporal structure of episodic hormone (LH and testosterone)
      secretion; (2) deconvolution analysis as a technique to quantify underlying
      pituitary and gonadal hormone secretory rates from the observed plasma hormone
      concentration profiles; (3) approximate entropy as a scale- and model-independent
      measure of the serial regularity or orderliness of the hormone release process
      over time; and (4) cross-approximate entropy (cross-ApEn) to quantify joint
      asynchrony between two concurrent pulse trains without confounding by variable
      lag. These new methodologies are introduced and reviewed briefly, a stochastic
      differential equation feedback construct alluded to, and the resultant insights
      into distinct alterations of the aging male gonadotropic axis highlighted. In
      summary, the new experimental strategies of intensified venous sampling,
      multiparameter deconvolution analysis, approximate entropy, and cross-approximate
      entropy unveil new mechanisms underlying dynamic neuroendocrine-axis activity, as
      exemplified by aging-associated disruption of the human male reproductive axis.

PMID- 9154221
TI  - Molecular psychiatry joins biomedicine.

PMID- 9154222
TI  - A cytoplasmically inherited prionlike genetic element in yeast.

PMID- 9154223
TI  - Peptides, sleep and cortistatin.

PMID- 9154224
TI  - Reductionist science and Alzheimer's disease: redoubling our effort in redox
      chemistry.

PMID- 9154225
TI  - Age-related alterations of the N-methyl-D-aspartate receptor in the dentate
      gyrus.

PMID- 9154226
TI  - Acetylcholinesterase is a senile plaque component that promotes assembly of
      amyloid beta-peptide into Alzheimer's filaments.

PMID- 9154227
TI  - Superoxide involvement in excitotoxicity: a SOD-mimetic holds promise as a novel
      neuroprotective agent.

PMID- 9154228
TI  - Muscarinic M1 receptors in schizophrenia.

PMID- 9154229
TI  - Functional neuroimaging of hallucinations in schizophrenia: toward an integration
      of bottom-up and top-down approaches.
AB  - Hallucinations in schizophrenia represent an important clinical problem, an
      interesting neuropsychological enigma, and a significant challenge for
      neuroscientific research. Functional neuroimaging techniques allow the in vivo,
      systems-level study of brain dysfunction underlying this debilitating symptom.
      Clinical and scientific vantage points that can inform the design and
      interpretation of functional neuroimaging studies of schizophrenic hallucinations
      are outlined. These include considerations of the phenomenology of
      hallucinations, the relationship of hallucinations to other symptoms of
      schizophrenia, and the neuropsychological functions that are thought to be
      disrupted in hallucinations. They also include the anatomical and chemical brain
      systems in which abnormalities are implicated in schizophrenia, the neurologic
      conditions in which hallucinations may occur, the neurochemical contexts that are
      associated with hallucinations, and the methodologic details of the functional
      neuroimaging techniques employed. Bottom-up and top-down functional neuroimaging
      strategies for the investigation of schizophrenic hallucinations with positron
      emission tomography (PET), single photon emission computed tomography (SPECT) and
      functional magnetic resonance imaging (fMRI) are reviewed. Bottom-up approaches
      start with or measure the biology associated with hallucinations. Top-down
      approaches start from the specific neuropsychological dysfunctions thought to be
      associated with hallucinations. The distributed brain regions, systems and
      functions implicated in schizophrenic hallucination formation are then discussed
      in the context of an integration of bottom-up and top-down approaches. Focus is
      placed upon abnormalities in the functions of, and interactions among, auditory
      linguistic association cortices, caudal and rostral limbic/paralimbic systems,
      prefrontal cortices, ventral striatum and (non-specific projection and
      associative) thalamic nuclei, as well as upon the glutamatergic, GABAergic and
      ventral tegmental dopaminergic modulation of these systems.

PMID- 9154230
TI  - Mad cows meet mad yeast: the prion hypothesis.
AB  - Obscure work on the inheritance of two peculiar genetic traits in yeast has
      recently collided with work on infectious, neurodegenerative diseases in mammals.
      The impact illuminates both fields. The yeast work reveals a new mechanism of
      genetic variation that is based on differences in protein conformation rather
      than differences in nucleic acid. In the light of this work the prion hypothesis
      for transmissible neurodegenerative disease no longer seems so bizarre. Indeed,
      the mammalian prion hypothesis is now placed within a larger framework that is
      likely to be of universal importance in biology. Yeast prions, as the genetic
      elements are called, can be cured, offering new insights into the molecular
      processes involved in protein-based inheritance and new hope for the treatment of
      neurodegenerative diseases in man.

PMID- 9154231
TI  - The subiculum: a potential site of action for novel antipsychotic drugs?
AB  - In this article, recent information from neuropathological studies in humans and
      behavioural and electrophysiological/pharmacological studies in rats is used to
      examine the hypothesis that the subiculum, the major output region of the
      hippocampal formation, may contain sites of action for novel antipsychotic drugs.
      In the first section, the possible interactions between subicular neurons and the
      sites at which existing antipsychotic drugs act are discussed. These include the
      interaction implied by convergence of subicular and dopaminergic inputs to the
      nucleus accumbens. The second section concentrates upon subicular involvement in
      animal behaviours that are thought to be relevant to schizophrenia, which, in
      rats, include Latent inhibition and Pre-pulse inhibition of Acoustic Startle.
      Involvement of the subiculum in the neuropathology of schizophrenia is discussed
      in the third section. However, few neuropathological studies comment specifically
      on the subiculum. Those which suggest involvement tend to be recent and, as yet,
      have not all been replicated. Finally, there is discussion of the possibility
      that the subiculum contains chemical sites at which drugs could act specifically
      to produce appropriate physiological effects. Potential sites include, but are
      not necessarily restricted to, particular ion channels in electrophysiologically
      defined subclasses of subicular pyramidal neurons, the receptors for
      neuromodulatory peptides such as somatostatin and cholecystokinin, and the enzyme
      nitric oxide synthase. It is concluded that a wide range of clinical and basic
      neuroscience disciplines has provided evidence which, especially when viewed as a
      whole, is consistent with the hypothesis that the subiculum is a potential site
      of action for novel antipsychotic drugs.

PMID- 9154232
TI  - The association between the dopamine D4 receptor (D4DR) 16 amino acid repeat
      polymorphism and novelty seeking.
AB  - Ebstein and colleagues have recently reported a significant association between
      the 7-repeat allele of the dopamine D4 receptor (D4DR) 16 amino acid repeat
      polymorphism and the personality trait of Novelty Seeking (NS) in 124 Israeli
      subjects. This study, and another study conducted in the US (although with a
      different personality measure) that observed a similar association, have
      generated wide interest in the identification of the genes involved in
      personality variation. We have determined D4DR genotypes in two groups of Finnish
      subjects; 193 psychiatrically screened normal controls and 138 alcoholic
      offenders and assessed NS with the Tridimensional Personality Questionnaire
      (TPQ). In normals, we find no significant association between NS and the 7-repeat
      allele despite similar allele frequencies and the use of the same personality
      measure as Ebstein et al. The group of alcoholic offenders have significantly
      higher NS than normals, however we fail to replicate the previous association in
      this group and, in fact, find a significant association in the opposite direction
      as previously observed. These data suggest that D4DR may require re-evaluation as
      a candidate gene for personality variation.

PMID- 9154233
TI  - The human serotonin 7 (5-HT7) receptor gene: genomic organization and systematic
      mutation screening in schizophrenia and bipolar affective disorder.
AB  - In the present study, we evaluated the possible contribution of genetic variation
      of the serotonin 5-HT7 receptor to the development of schizophrenia and bipolar
      affective disorder. Cloning and characterization of exon-flanking intronic
      sequences enabled us to investigate the whole coding region and the exon-intron
      boundaries of the human 5-HT7 receptor gene. Using single-strand conformational
      analysis, we screened for presence of DNA sequence variation in a sample of 137
      unrelated individuals including 45 schizophrenic and 46 bipolar affective
      patients, as well as 46 healthy controls. We detected two rare naturally
      occurring receptor variants (Pro-279-Leu, Thr-92-Lys) and a silent nucleotide
      substitution (A-->G) at position +1233. The occurrence of the Pro-279-Leu and Thr
      92-Lys substitutions was studied in an extended sample of patients (n = 462) and
      controls (n = 335). The Leu-279 variant was found in similar frequency in all
      groups, indicating that presence of this variant is not causally related to the
      development of schizophrenia or bipolar affective disorder. The Lys-92 variant
      was found in a single individual who suffered from bipolar affective disorder.
      Investigation of the patient's family revealed independent segregation between
      the Lys-92 variant and psychiatric illness. Our data suggests that genetic
      variation of the 5-HT7 receptor does not play a major role in the development of
      bipolar affective disorder and schizophrenia.

PMID- 9154234
TI  - Mechanism of amyloid beta-peptide (1-42) toxicity in PC12 cells.
AB  - Amyloid beta-peptide (A beta) deposition and loss of cholinergic neurons are
      characteristics of Alzheimer's disease. There is evidence that A beta is
      neurotoxic. The role of signal transduction pathways on A beta-induced toxicity
      in PC12 cells was investigated. Our results revealed that A beta-induced
      arachidonic acid was released in a time-dependent manner. Inhibitors of
      cyclooxygenase (1 microM indomethacin) and lipooxygenase (100 microM
      nordihydroguairetic acid) protected PC12 cells against A beta-induced toxicity.
      These data suggest that A beta toxicity is mediated by activation of the
      arachidonic acid cascade. Furthermore, protein kinase C activators (phorbol ester
      and 1-oleyl-2-acetyl-glycerol) and tacrine reversed A beta-induced toxicity.
      These results suggest that A beta toxicity can be modulated by manipulating
      signal transduction pathways and may provide the basis for novel therapeutic
      interventions.

PMID- 9154235
TI  - Scanning the genome with 1772 microsatellite markers in search of a bipolar
      disorder susceptibility gene.
AB  - Bipolar disorder affects approximately 1% of the population and there is evidence
      that genetic factors play an important role in the production of symptoms. We
      undertook a genetic linkage study for the discovery of a major locus conferring
      susceptibility for bipolar illness in an Old Order Amish pedigree. Our study took
      advantage of publicly available phenotypic and genotypic information, the latter
      as a byproduct of the human genome project effort. We present a genomic scan
      using 1772 polymorphic genetic markers and we suggest candidate genetic regions
      for harboring a bipolar disorder susceptibility gene.

PMID- 9154236
TI  - Complexity measures in molecular psychiatry.
AB  - The most frequently used measures in behavioral research are distribution
      determined measures that provide a quantitative determination of the relative
      frequency of a specified behavior. These measures are, however, insensitive to
      the sequence of behaviors. Complexity measures address this deficiency. Several
      sequence-sensitive measures including the topological entropy, metric entropy,
      algorithmic complexity and stochastic model complexity will be described. Several
      applications to psychiatric research will also be discussed. These applications
      include the characterization of changes in animal behavior in response to CNS
      active drugs and the analysis of single-unit interspike interval spike trains.
      Clinical applications include the analysis of electromyographic and
      electroencephalographic signals, the examination of choice task behavior in
      clinical populations, and protocol analysis.

PMID- 9154237
TI  - Searching for a molecular address in the brain.

PMID- 9154239
TI  - The augmenting response, a form of short-term plasticity in the neocortex that is
      modulated by behavioral state.

PMID- 9154238
TI  - Tissue targeting with phage peptide libraries.

PMID- 9154240
TI  - Fasted and finicky without fight or flight: selective anorexic actions of a novel
      stress-related neuropeptide.

PMID- 9154241
TI  - Basal ganglia and cerebellar output influences non-motor function.

PMID- 9154242
TI  - Candidate gene association studies in psychiatric genetics: a SERTain future?

PMID- 9154243
TI  - The 5-HT hypothesis of depression revisited.

PMID- 9154244
TI  - Unraveling the molecular pathway of Alzheimer's disease: research about
      presenilins gathers momentum.
AB  - Missense mutations of the presenilins (PS1 and PS2) first identified about one
      year ago are responsible for the majority of autosomal dominant familial
      Alzheimer's disease cases. Recent studies suggesting that these mutations exert
      their disastrous effect by elevating the levels of the longer form of beta
      amyloid (A beta 42) are reviewed.

PMID- 9154245
TI  - The contribution of astrocytes to the 18F-2-deoxyglucose signal in PET activation
      studies.
AB  - With the development of functional brain imaging techniques such as Positron
      Emission Tomography (PET) and functional Magnetic Resonance Imaging (fMRI) it has
      become possible to visualize brain areas that are activated by a variety of
      sensory, motor or cognitive tasks. This technological progress has permitted a
      kind of in vivo functional neuroanatomy which has led to the identification of
      neural circuits subserving specific brain functions. Metabolic processes linked
      to neuronal activity--such as blood flow, glucose utilization and oxygen
      consumption--provide the signals detected with most functional brain-imaging
      techniques. These metabolic indices have been examined in a variety of
      psychiatric and neurological disorders. This article focuses on the use of
      (18F)fluoro-2-deoxyglucose (FDG)-PET in the study of psychiatric disorders; it is
      mainly intended to bring a novel perspective, based on recent experimental data,
      on the cellular and molecular mechanisms that underlie the FDG-based PET imaging.
      These new observations point to a critical role of a particular glial cell type,
      the astrocyte, in coupling neuronal activity to glucose utilization. Indeed it
      appears that in response to glutamate released by active neurons, glucose is
      predominantly taken up by specialized astrocytic processes, the end-feet, which
      surround brain capillaries; glucose is then metabolized to lactate, which
      provides a preferred energy substrate for neurons. These data support the notion
      that astrocytes markedly contribute to the FDG-PET signal. This perspective may
      also provide renewed insights for the interpretation of FDG-PET studies in
      psychiatric disorders.

PMID- 9154247
TI  - DRD2, DRD3 and 5HT2A receptor genes polymorphisms in obsessive-compulsive
      disorder.
AB  - We performed an association analysis of the DRD2, DRD3 and 5HT2A genes
      polymorphisms in 67 Obsessive-Compulsive Disorder (OCD) patients and 54 healthy
      controls. There were no statistically significant differences in genotype or
      allele frequencies for any of the polymorphisms studied between OCD subjects and
      controls. For the subgrouped analysis, no results were significant after
      correction for multiple testing, although homozygosity of DRD2/A2A2 in subjects
      displaying vocal or motor tics approached significance compared to controls
      (Fisher exact test, P = 0.008). Our results may follow the notion that OCD
      patients with tics represent a different genetic subtype of the disease.

PMID- 9154246
TI  - A novel functional polymorphism within the promoter of the serotonin transporter
      gene: possible role in susceptibility to affective disorders.
AB  - The serotonin transporter (5-HTT) is a candidate locus for aetiological
      involvement in affective disorders. Biochemical studies in suicides and depressed
      patients suggest that 5-HT uptake function is frequently reduced in affective
      illness. Furthermore, 5-HTT is targeted by widely used antidepressant drugs such
      as fluoxetine. We have performed an association study of a short variant of the 5
      HTT-linked polymorphic region (5-HTTLPR), which restricts transcriptional
      activity of the 5-HTT promoter leading to low functional expression of the 5-HTT,
      in 454 patients with bipolar or unipolar affective disorder and 570 controls,
      derived from three European Centres (London, Milan and Wurzburg). In all three
      centres, the frequency of the low activity allele was higher in patients than in
      controls (50% vs 45% in London, 45% vs 43% in Milan, 47% vs 40% in Wurzburg).
      Although these differences were not individually significant, a stratified
      analysis of all three samples gave a significant overall odds ratio of 1.23 (95%
      confidence interval 1.02-1.49, P = 0.03). The excess of the homozygous low
      activity genotype among the patients was even greater (odds ratio 1.53, 95%
      confidence interval 1.04-2.23, P = 0.02), suggesting partial recessively of the
      low-activity allele. Given the functional role of 5-HTT, our findings suggest
      that 5-HTTLPR-dependent variation in functional 5-HTT expression is a potential
      genetic susceptibility factor for affective disorders. If this finding is
      replicated, further work on genetic variants with low 5-HTT activity may
      facilitate the differential diagnosis of affective disorders, the assessment of
      suicidal behaviour, and the prediction of good clinical response to
      antidepressants.

PMID- 9154248
TI  - Individuals with schizophrenia have an increased incidence of the H2R649G allele
      for the histamine H2 receptor gene.
AB  - We have previously described an allelic variant of the human H2R, nominated the
      H2R649G allele. This allele contains an adenine-->guanidine substitution at base
      649, which introduces an additional TaqI restriction endonuclease site into the
      gene. With this in mind, we have investigated allelic polymorphism of this
      receptor and its association with schizophrenia. H2R DNA from 47 schizophrenic
      patients and 46 control subjects was amplified by the polymerase chain reaction
      (PCR). These PCR products were analyzed by observing TaqI cleavage patterns and
      single-stranded conformational polymorphisms. It was found that the H2R649G
      allele was 1.8 times more frequent in the schizophrenic population (chi 2 test P
      < 0.01). In addition, schizophrenic individuals were 2.8 times more likely to be
      homozygous for the H2R649G allele than the control population, (chi 2 test P <
      0.05). These data place the attributable fraction for possession of the H2R649G
      allele at 28.4%.

PMID- 9154249
TI  - GTP gamma S and forskolin-stimulated adenylyl cyclase activity in post-mortem
      brain from depressed suicides and controls.
AB  - We have measured basal, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and
      forskolin-stimulated adenylyl cyclase activity in samples of frontal and parietal
      cortex obtained at post-mortem from suicides, with a firm retrospective diagnosis
      of depression. The suicides were divided into those free of antidepressants and
      those receiving antidepressants. Each suicide was individually compared to a
      gender and age-matched control. Although we found no significant differences in
      adenylyl cyclase activity between controls and either antidepressant-free or
      antidepressant-treated suicides, there was a trend for lower stimulated adenylyl
      cyclase activity in suicides.

PMID- 9154250
TI  - Dysthymia in neurological disorders.
AB  - Dysthymia is characterized by long-lasting periods of lowered mood.
      Epidemiological studies in the USA and Europe have demonstrated that the
      prevalence of dysthymia is at least 3% of the general population. Its pervasive
      occurrence makes dysthymia a public health problem worldwide. One feature of this
      disorder is its co-occurrence with medical and neurological disorders. A World
      Health Organization meeting on dysthymia in neurological disorders was held in
      Geneva, 1-3 July 1996 to address this topic. Some of the major goals of this
      meeting were to clarify the definition of dysthymia in the presence of
      neurological disorders and to evaluate current research in the field, to point
      out new areas for investigation, and to discuss current psychological and
      pharmacological treatments for dysthymia in neurological disorders. The potential
      roles of neuroendocrine and molecular mechanisms in dysthymia were identified
      through specific problems related to dysthymia occurring in disorders such as
      Parkinson's disease, Alzheimer's disease, stroke, multiple sclerosis and
      epilepsy. This meeting provided direction and opportunity for future studies in
      the under-recognized and under-investigated relationship between dysthymia and
      neurological disorders.

PMID- 9154251
TI  - Meta-analysis of adolescent drug prevention programs: results of the 1993 meta
      analysis.

PMID- 9154253
TI  - Meta-analysis and models of substance abuse prevention.

PMID- 9154252
TI  - Validity of integrity tests for predicting drug and alcohol abuse: a meta
      analysis.

PMID- 9154254
TI  - Realities of the effect size calculation process: considerations for beginning
      meta-analysts.

PMID- 9154255
TI  - Issues and challenges in coding interventions for meta-analysis of prevention
      research.

PMID- 9154256
TI  - Experiments versus quasi-experiments: do they yield the same answer?

PMID- 9154257
TI  - Drawing generalized causal inferences based on meta-analysis.

PMID- 9154258
TI  - Issues in classification in meta-analysis in substance abuse prevention research.

PMID- 9154259
TI  - Improving meta-analysis for policy purposes.

PMID- 9154260
TI  - Using linked meta-analysis to build policy models.

PMID- 9154261
TI  - Some limiting factors in meta-analysis.

PMID- 9154262
TI  - The influence of comorbid major depression and substance use disorders on alcohol
      and drug treatment: results of a national survey.

PMID- 9154263
TI  - Challenges in assessing substance use patterns in persons with comorbid mental
      and addictive disorders.

PMID- 9154264
TI  - Anxiety disorders, comorbid substance abuse, and benzodiazepine discontinuation:
      implications for treatment.

PMID- 9154265
TI  - Cigarette smoking and its comorbidity.

PMID- 9154266
TI  - Treatment of depression in drug-dependent patients: effects on mood and drug use.

PMID- 9154267
TI  - The course and treatment of substance use disorder in persons with severe mental
      illness.

PMID- 9154268
TI  - Substance use and HIV risk among people with severe mental illness.

PMID- 9154269
TI  - Depression, substance use, and sexual orientation as cofactors in HIV-1 infected
      men: cross-cultural comparisons.

PMID- 9154271
TI  - Prostaglandins: a new approach to glaucoma management with a new, intriguing side
      effect.
AB  - This introductory overview considers the advantages of a class of local hormones
      the prostaglandins (PGs)-for the management of intraocular pressure (IOP) in
      glaucoma, over agonists and antagonists of neurotransmitters that dominated this
      field in the 20th century. PGs and PG analogues, in particular esterified prodrug
      forms of PGF2 alpha, are effective ocular hypotensive agents, but cause some
      conjunctival hyperemia and corneal sensory irritation at higher concentrations.
      Based on structure-activity studies, a 17-phenyl PGF2 alpha prodrug, latanoprost
      (PhXA41), was found to have a greatly improved therapeutic index, without
      compromising the ocular hypotensive potency of PGF2 alpha prodrugs. The IOP
      lowering mechanism of such PGF2 alpha s, increased uveoscleral outflow, can be
      expected to have great physiologic advantages, especially with respect to normal
      tension glaucoma, over most currently used ocular hypotensive drugs. The
      introduction of this new approach has already led to a new insight into the
      control and clinical significance of this outflow route. Similarly, the newly
      discovered ocular side effect, PG-induced increase in iridial pigmentation, can
      be expected to provide insight into the oculo-protective role of iridial
      melanocytes and into the punative association between a decline in the ocular
      melanin system and the vulnerability of the eye to some age-related diseases.

PMID- 9154270
TI  - Psychiatric symptoms, risky behavior, and HIV infection.
AB  - These data are internally consistent and lead to several conclusions, as follows:
      Elevated levels of psychiatric symptoms were found among IDUs in methadone
      treatment as compared to their counterparts who were out of treatment. IVDUs who
      entered treatment had higher symptom levels than those who did not enter
      treatment. Higher symptom levels were found among injectors than noninjectors,
      and needle sharers had especially high psychiatric symptom levels. Higher symptom
      levels were found among those who seroconverted in the 6 months following
      notification, but not thereafter. Symptom levels did not distinguish between HIV
      positive and HIV-negative individuals 24 months following notification of
      seropositivity. Taken together, these findings indicate that elevated psychiatric
      symptoms are risk factors for continued high risk behavior, as well as for
      seroconversion. The data add to those of Brooner and colleagues (1993), who
      demonstrated that ASPD serves as a risk factor for HIV infection. The fact that
      antisocial personality disorder and psychiatric severity are associated with
      risky behavior and with actual HIV infection further expands earlier findings
      showing that these two factors are associated with poorer treatment outcome.
      Other axis II disorders (e.g., borderline or narcissistic), as well as other axis
      I disorders with high symptom levels that were not well represented in these
      studies (schizophrenia, manic depressive illness), may also show similar elevated
      rates of risky behavior and seroconversion, although there is a scarcity of data
      currently available to assess the risk behavior of these patients. The evidence
      from treatment studies that psychiatrically focused therapies, when combined with
      substance abuse treatment, can improve overall outcome for patients with
      clinically significant levels of psychiatric symptoms may be relevant in the
      design of future risk reduction efforts. That is, these treatment outcome studies
      may serve as a starting point for exploring the feasibility and efficacy of using
      psychiatrically focused treatment to reduce risky behavior and HIV infection
      among psychiatrically symptomatic IDUs.

PMID- 9154272
TI  - The molecular biology and ocular distribution of prostanoid receptors.
AB  - Enormous progress has been made in the characterization of prostanoid receptors
      during the past five years. Molecular biological studies have enabled structural
      identification of all the human prostanoid receptors that had been proposed
      according to pharmacological criteria. The pharmacological classification
      proposed different receptor subtypes for prostaglandins D2, E2, F2 alpha, I2 and
      thromboxane A2 which were termed DP, EP, FP, IP and TP, respectively. Further
      subdivision for only the EP receptor has been reported and EP1, EP2, EP3, and EP4
      subtypes have been unequivocally identified. The molecular structure of all
      prostanoid receptors is typical of that for G protein-coupled receptors and
      consists of seven alpha-helical transmembrane domains, three extracellular loops
      and an amino terminus, and three intracellular loops and a carboxyl terminus.
      Interestingly, mRNA alternative splice variants of the carboxyl termini have been
      found to determine G protein interactions for the EP3 receptor. Application of
      molecular biological techniques is beginning to make an impact in ocular
      research, where precise localization of receptors is difficult by more
      traditional methods because of the diminutive size of most ocular tissues. In
      situ hybridization and immunohistochemical studies using antibodies against the
      cloned human FP receptor have already suggested an unexpectedly wide distribution
      in the monkey eye. Transgenic studies involving FP receptor knock-out animals may
      provide future insight into the role of this receptor in glaucoma. However, since
      prostaglandins are extraordinarily effective in reducing intraocular pressure, it
      follows that traditional physiological and pharmacological studies retain a key
      role in glaucoma research. Studies in perfused human anterior segment organ
      culture have revealed that although prostaglandin F2 alpha does not facilitate
      trabecular aqueous humor outflow, prostaglandin E1 does increase trabecular
      outflow. Thus, different prostanoids may lower intraocular pressure by distinctly
      different mechanisms of action. Recent studies also indicate that prostanoids may
      exert a beneficial effect on retinal blood perfusion and may even act as
      neuroprotective agents.

PMID- 9154273
TI  - Signal transduction and gene expression in the eye: a contemporary view of the
      pro-inflammatory, anti-inflammatory and modulatory roles of prostaglandins and
      other bioactive lipids.
AB  - Eye tissues respond to physiological and pathophysiological stimuli by the
      activation of phospholipases and the consequent release from membrane
      phospholipids of biologically active metabolites. These rapid events have
      profound effects on long-term ocular physiology. Activation of phospholipase A2
      is the first step in the synthesis of two important classes of lipid second
      messengers, the eicosanoids and platelet-activating factor (PAF). PAF accumulates
      in the cornea in response to injury. It has been shown to stimulate
      metalloproteinase gene expression in the corneal epithelium, and is, thus,
      implicated in the extracellular matrix remodeling that accompanies wound healing
      and ulceration. PAF antagonists confer protection in animal models of acute and
      chronic anterior segment inflammation, and block the PAF-enhanced glutamate
      release from retina. The latter effect suggests a role for PAF in glaucomatous
      neuronal damage. The eicosanoids, in particular the prostaglandins, have long
      been implicated in the pathophysiology of ocular inflammation and there is
      pharmacological evidence for their role in the regulation of intraocular
      pressure. The induction by PAF of the inducible prostaglandin synthase in neurons
      and in the corneal epithelium provides a link between the actions of these two
      lipid second messengers. There may be thresholds of lipid second messenger
      concentrations which govern their activities as physiological, defensive, or
      harmful.

PMID- 9154274
TI  - Cyclooxygenase-2 inhibitors: a new approach to the therapy of ocular
      inflammation.
AB  - Prostaglandins (PGs) can be synthesized through the activities of two
      cyclooxygenase (COX) isoforms. COX-1 is constitutively expressed in most tissues
      and its activity provides for the relative small amounts of PGs required for the
      mediation and modulation of normal physiological functions. In inflammatory
      conditions, COX-2 is rapidly induced by cytokines, growth factors and bacterial
      endotoxin, and its enzymatic activity accounts for the large amounts of PGs
      produced during inflammation. The currently used nonsteroidal anti-inflammatory
      drugs (NSAIDs) are nonselective inhibitors of both COX isoforms. Inhibition of
      COX-2 leads to the therapeutically desired inhibition of the synthesis of pro
      inflammatory PGs, but at the same time produces side effects associated with
      inhibition of COX-1 and the consequent suppression of the production of PGs
      necessary for normal cellular functions. Selective inhibition of COX-2 expression
      explains, at least in part, the potent anti-inflammatory activity of
      corticosteroids. However, the systemic and ocular side effects of these steroids
      have greatly limited their use, especially their long-term use for the management
      of chronic inflammatory conditions. The current effort to develop highly
      selective nonsteroidal COX-2 inhibitors for the treatment of arthritis and other
      inflammatory diseases can also be expected to yield a new approach to the
      treatment of uveitis and other ocular inflammatory conditions. This new class of
      NSAIDs will provide anti-inflammatory and analgesic activity while circumventing
      the most serious side effects of the current available NSAIDs, resulting from
      their inhibition of the physiologically required COX-1 activity.

PMID- 9154275
TI  - The prostaglandin transporter is widely expressed in ocular tissues.
AB  - Prostaglandins (PGs) play important physiological and therapeutic roles in the
      eye. Our laboratory recently identified a novel PG transporter in the rat that we
      call "PGT" (Science 268:866, 1995). We have also recently cloned the human PGT
      cDNA (J Clin Invest 98:1142, 1996). To determine whether PGT might play a role in
      human ocular tissues, we performed Northern blot analysis of RNA obtained from
      human ocular tissues and from the nonpigmented ciliary epithelium cell line "ODM
      2." PGT transcripts were clearly evident in all ocular tissues. Given that the
      functional profile of PGT expressed in vitro strongly suggests a role in PG
      uptake and degradation, the present results suggest that PGT may function in
      various regions of the human eye for purposes of terminating the signal(s)
      produced by locally-synthesized PGs.

PMID- 9154276
TI  - Structure-activity relationships and receptor profiles of some ocular hypotensive
      prostanoids.
AB  - A novel series of prostaglandin F (PGF) analogues have been prepared and
      evaluated in vivo and in vitro. Their intraocular pressure (IOP) lowering effects
      and potential side-effects, as prodrug eye drops, have been tested in cats,
      monkeys and rabbits. Furthermore, the PGF-analogues were tested as free acids for
      FP-receptor agonistic activity on cat iris sphincter. The results were compared
      to that of PGF2 alpha (C#1). Based on the structure-activity relationship
      investigations, inversion of the configuration, at carbon-9 (C#3) or carbon-11
      (C#4), changes the potency and the receptor profile of PGF2 alpha. Replacement
      part of the omega-chain of PGF2 alpha with a benzene ring changes the potency and
      receptor profile of PGF2 alpha. The optimal position of the benzene ring is on
      carbon-17, 17-phenyl-18,19,20-trinor PGF2 alpha-isopropyl ester (C#8), and
      exhibited a much higher therapeutic index in the eye than PGF2 alpha or its
      ester. The biological activity of different substituents on the C#8 benzene ring
      have also been studied. Interestingly, introduction of a methyl group at
      positions 2 or 3 of the benzene ring (C#16 or C#17) affords compounds which are
      biologically more active than the methyl group at the 4-position (C#18).
      Furthermore, one of the analogues 13,14-dihydro-17-phenyl-18,19,20-trinor PGF2
      alpha-isopropyl ester (latanoprost), has been found in clinical studies to be a
      highly potent and efficacious IOP-reducing agent for the treatment of glaucoma.

PMID- 9154277
TI  - Prostaglandin action on ciliary smooth muscle extracellular matrix metabolism:
      implications for uveoscleral outflow.
AB  - The cellular mechanisms mediating intraocular pressure reduction following
      topical prostaglandin (PG) treatments are poorly understood. To determine if PG
      treatments might induce altered metabolism of extracellular matrix surrounding
      ciliary muscle cells, confluent human ciliary smooth muscle cell cultures were
      exposed to PGF 2 alpha' 17-phenyltrinor-PGF2 alpha' or 11-deoxy-PGE1 for one to
      four days and the distributions of collagen types I, III and IV as well as
      laminin were determined immunocytochemically. In addition, collagen type IV and
      promatrix metalloproteinase III (proMMP-3) content within treated cultures was
      determined using sandwich ELISAs. Compared with vehicle-treated cultures, there
      were substantial reductions in the density and branching of the collagen type IV
      immunoreactive lattice accompanied by thickening of remaining strands in all PG
      treated cultures. Similar changes were seen in the distribution of laminin within
      all PG-treated cultures. Reductions in collagen type III immunoreactivity were
      seen in cultures treated with either PGF2 alpha or 17-phenyltrinor-PGF2 alpha. No
      changes were observed in collagen type I immunoreactivity. Quantitative analyses
      revealed increased amounts of collagen type IV in both the culture medium and in
      extracts of the cell layer in all PG-treated cultures. In addition, there were
      substantial increases in the concentrations of proMMP-3 in all PG-treated
      cultures. These results indicate that PGs induce increased turnover and
      remodeling of ECM adjacent to ciliary muscle cells. Such changes may contribute
      to increased uveoscleral outflow in vivo following topical PG treatment.

PMID- 9154278
TI  - Initial clinical studies with prostaglandins and their analogues.
AB  - Several prostaglandins (PGs), their prodrugs, and their analogues have been shown
      to reduce intraocular pressure (IOP) in normotensive volunteers and in patients
      with elevated IOP. Initial clinical trials demonstrated efficacy with most of
      these agents, but a PGE2 analogue, PGD2, and BW245C (an analogue selective for
      the DP-receptor) cause an initial rise in IOP with a minimal subsequent
      reduction. Although PGF2 alpha tromethamine salt, PGF2 alpha-isopropyl ester
      (PGF2 alpha-IE), and 15-propionate-PGF2 alpha-IE are all very effective in
      reducing IOP, they produce unacceptable side effects, including conjunctival
      hyperemia and ocular irritation. Isopropyl unoprostone, a 22-carbon chain PGF2
      alpha metabolite, produces a 10-25% reduction in IOP lasting approximately 2-5
      hours, is well tolerated, and is commercially available for use in Japan. 17
      phenyl substituted PGF2 alpha-IE analogues, such as PhXA34 or latanoprost,
      effectively reduce IOP by 30-40% for at least 24 hours, and are very well
      tolerated with minimal conjunctival hyperemia and without irritation. Latanoprost
      is the more potent 15R-epimer of PhXA34, and has become a useful agent in
      glaucoma therapy.

PMID- 9154279
TI  - Effects of exogenous prostaglandins on aqueous humor dynamics and blood-aqueous
      barrier function.
AB  - Topical prostaglandins (PGs) are very effective at reducing intraocular pressure
      (IOP) in a variety of animals and in humans with relatively few side effects. The
      mechanisms of action of several PGs, their prodrugs and analogues have been
      studied in rabbits, cats, monkeys and humans. PGF2 alpha and its analogues
      evaluated in monkeys include PGF2 alpha-tromethamine salt, PGF2 alpha 
      isopropylester (-IE), S-1033, PhXA34, PhDH100A and latanoprost (PhXA41). Aqueous
      flow and outflow facility are either increased or remain unchanged by these
      agents. PGF2 alpha-IE, PHXA34, PhDH100A and latanoprost increase uveoscleral
      outflow, accounting for most of the IOP reduction. PGA2 in cats increases aqueous
      flow and outflow facility, but it reduces IOP primarily by stimulating
      uveoscleral outflow. The PGD2 analogue BW245C is unique in that it is the only PG
      that decreases aqueous flow. Mechanistic studies in humans have been performed
      with PGF2 alpha -IE, unoprostone, PhXA34 and latanoprost. In two clinical studies
      with latanoprost, a significant increase in uveoscleral outflow was found which,
      as in animals, accounts for most of the IOP reduction. A slight but inconsistent
      increase in outflow facility may also be involved. The doses tested had minimal
      effects on the permeability of the blood-aqueous barrier (BAB). In vitro studies
      of human tissue have been conducted to elucidate the PG effect on outflow
      facility and uveoscleral outflow. Studies of isolated human anterior segment
      preparations show that PGE2 increases outflow facility whereas PGF2 alpha has no
      measurable effect on this parameter. Studies of human ciliary muscle cells in
      tissue culture indicate that PGs may directly modulate extracellular matrix
      metabolism, which may be related to the increased uveoscleral drainage. This
      review summarizes in vitro and in vivo studies of the effects of PGs on aqueous
      humor dynamics and BAB integrity in humans, cats and monkeys.

PMID- 9154280
TI  - Clinical dose-regimen studies with latanoprost, a new ocular hypotensive PGF2
      alpha analogue.
AB  - This review summarizes recent short-term clinical studies evaluating the ocular
      hypotensive efficacy of different dose-regimens of latanoprost. When tested in
      ocular hypertensive and glaucoma patients concomitantly treated with timolol,
      0.006% latanoprost given only in the evening, was found to be more effective than
      the same concentration given in the morning and evening. In patients with open
      angle, pseudoexfoliation and normal tension glaucoma not receiving other
      treatment, once-daily 0.005% latanoprost monotherapy was more effective than
      twice-daily 0.0015% latanoprost treatment. No significant differences were found
      in conjunctival hyperemia, sensory irritation or blood-aqueous barrier
      permeability between these two treatment regimens. Although the ocular
      hypotensive efficacy of once-daily application of the lower concentration
      (0.0015%) latanoprost was not investigated, we would conclude, based on the
      studies reviewed here, that at a concentration of 0.005%, once-a-day dosing of
      latanoprost is highly effective in significantly reducing intraocular pressure,
      causing only minimal, clinically acceptable short-term ocular side effects.

PMID- 9154281
TI  - Fluorescein angiographic evaluation of the effect of latanoprost treatment on
      blood-retinal barrier integrity: a review of studies conducted on pseudophakic
      glaucoma patients and on phakic and aphakic monkeys.
AB  - Endogenous prostaglandins (PGs) have been claimed to play a role in the
      development of cystoid macular edema (CME). Two fluorescein angiographic studies
      evaluating the effect of latanoprost, a new ocular hypotensive PG analogue, on
      blood-retinal barrier integrity are, therefore, reviewed here. In the first
      study, six of eight unilaterally aphakic cynomolgus monkeys were treated
      bilaterally once daily for six months with 0.035% latanoprost (seven times the
      clinically used oculohypotensive concentration). Two of the animals served as
      controls. Fluorescein angiography of the fundus after one, three and six months
      of treatment revealed no leakage of fluorescein in any of the 16 eyes. In another
      study, pseudophakic eyes of 16 glaucoma patients who received twice-daily
      treatment with 0.006% latanoprost for four weeks were compared to eight patients
      treated with placebo. Biomicroscopic examination did not reveal any signs of CME
      and only one placebo-treated eye revealed a slight perifoveal leakage of
      fluorescein. These studies suggest that topically-applied latanoprost does not
      have a fluorescein angiographically detectable direct effect on the integrity of
      the blood-retinal barrier system in phakic or aphakic monkey eyes or in
      pseudophakic human eyes. This does not rule out the occurrence of CME in eyes
      more susceptible to CME, due to vitreous loss, posterior capsulotomy, or other
      postoperative situations. Especially in those eyes a study with latanoprost is
      proposed. Since, fluorescein angiography is a rather crude method of detecting
      abnormalities of the blood-retinal barriers, vitreous fluorometry in addition is
      suggested.

PMID- 9154282
TI  - Reduced intraocular pressure and increased ocular perfusion pressure in normal
      tension glaucoma: a review of short-term studies with three dose regimens of
      latanoprost treatment.
AB  - Currently used ocular hypotensive agents do not effectively lower intraocular
      pressure (IOP) in some normal-tension glaucoma (NTG) patients. The prostaglandin
      F2 alpha analogue, latanoprost, has been shown to reduce IOP in normal subjects
      and ocular hypertensive glaucoma patients by increasing uveoscleral outflow. This
      mechanism is expected to be particularly effective in the lower IOP range that is
      typical of NTG. To date, three dose regimens of latanoprost have been shown to
      reduce IOP significantly in NTG. The IOP reductions of 14.2% and 15% obtained
      with twice-daily application of 0.0015% and 0.006% latanoprost, respectively,
      were comparable to the modest IOP reduction that has been reported for other
      glaucoma drugs in NTG. In contrast, once-daily application of 0.005% latanoprost
      resulted in a 21.4% IOP reduction. In another study that included 24-hour
      monitoring of systemic blood pressure and heart rate in NTG patients, the ocular
      perfusion pressure was found to improve more on once-daily 0.005% latanoprost
      than on twice-daily treatment with 0.5% timolol. Thus, once-daily 0.005%
      latanoprost appears to be a more effective and more convenient ocular hypotensive
      agent for treating NTG than currently used glaucoma drugs. However, long-term
      studies will ultimately be needed to establish the efficacy of this new drug to
      delay or prevent the progression of visual field loss in normal tension glaucoma.

PMID- 9154283
TI  - The additive intraocular pressure-lowering effect of latanoprost in combined
      therapy with other ocular hypotensive agents.
AB  - Latanoprost, a prostaglandin F2 alpha analogue prodrug, has been shown to be an
      effective ocular hypotensive agent when used alone on ocular hypertensive or open
      angle glaucoma patients. In various studies, the ocular hypotensive effects of
      latanoprost have also been evaluated when used in addition to, or in combination
      with, other ocular hypotensive agents. Latanoprost produces an additional
      reduction of intraocular pressure (IOP) when used in combination with timolol,
      pilocarpine, acetazolamide and dipivefrin. These represent four different classes
      of glaucoma drugs-beta-adrenergic antagonists, cholinergic agonists, carbonic
      anhydrase inhibitors, and adrenergic agonists-all of which reduce the IOP by
      different mechanisms (reduction of aqueous humor production, increased outflow
      facility, or by a mixed effect on aqueous humor dynamics). All the available
      evidence shows that latanoprost produces a clinically significant additive ocular
      hypotensive effect when used in combination with any currently available ocular
      hypotensive agent.

PMID- 9154284
TI  - Clinical evaluation of UF-021 (Rescula; isopropyl unoprostone).
AB  - We have reviewed two Phase III clinical studies of isopropyl unoprostone
      conducted in Japan: a 12-week comparative study of 0.12% isopropyl unoprostone
      and 0.5% timolol, and a 52-week administration of two concentrations of isopropyl
      unoprostone in ocular hypertensive and primary open-angle glaucoma patients.
      These studies showed a similar ocular hypotensive effect of 0.12% isopropyl
      unoprostone to 0.5% timolol and a sustained ocular hypotensive effect of the drug
      for up to one year. Adverse reactions of isopropyl unoprostone were minor and
      similar to those of timolol. No pigmentary changes of the irides were noticed. In
      view of these results, isopropyl unoprostone seems to be a useful antiglaucoma
      medication.

PMID- 9154285
TI  - Phase III latanoprost studies in Scandinavia, the United Kingdom and the United
      States.
AB  - Three large, masked, multicenter studies are reviewed comparing the safety and
      efficacy of 0.005% latanoprost eyedrops given once daily to 0.5% timolol eyedrops
      given twice daily for six months in patients with elevated intraocular pressure
      (IOP). A total of 829 patients were recruited from centers in Scandinavia, the
      United Kingdom (UK) and the United States of America (USA). In addition, data are
      reviewed from the first 198 of these patients to complete an additional six
      months of latanoprost treatment in an openlabel study. In all centers, both
      latanoprost and timolol were very effective in reducing the diurnal IOP. In the
      UK, both drugs reduced the IOP by 34%. In the USA, latanoprost was more effective
      than timolol, reducing IOP by 27% compared to 20%. In Scandinavia, latanoprost
      was given for three months in the evening and for three months in the morning
      while timolol was given twice daily for six months. Latanoprost given in the
      evening reduced IOP (35% reduction) significantly (p < 0.001) more than
      latanoprost given in the morning (31% reduction) and timolol given twice daily
      (27% reduction). Darkening of the iris color occurred in 7% of eyes treated with
      latanoprost for six months. A clinical evaluation of eyes with increased
      pigmentation, as well as preclinical studies; suggest that this side effect is a
      cosmetic problem in patients treated unilaterally. Other side effects were slight
      and not clinically significant. After one year of treatment with latanoprost in
      198 patients, the IOP reduction of 32% was maintained. There was no loss of
      efficacy and no significant increase in the incidence of side effects or adverse
      events other than iris color darkening, which occurred or was suspected in 12%.
      These results demonstrate that latanoprost is a valuable drug for the treatment
      of chronic open angle glaucoma.

PMID- 9154286
TI  - The lack of respiratory effects of the ocular hypotensive drug latanoprost in
      patients with moderate-steroid treated asthma.
AB  - The use of beta blockers for glaucoma treatment may cause serious
      bronchoconstriction in patients with chronic obstructive pulmonary disease. The
      synthetic prostaglandin (PG) F2 alpha-analogue latanoprost (13,14,dihydro-17
      phenyl-18,19,20-trinor-PGF-2-alpha-iso propylester) represents a new class of
      drugs for glaucoma treatment. In this study the pulmonary tolerability to
      latanoprost in 12 healthy volunteers and 11 (one withdrawal due to a sty before
      latanoprost treatment) subjects with moderate but stable steroid-treated
      intrinsic asthma was examined. Asthmatic subjects received 30 microliters of
      vehicle (placebo) at the scheduled administration times on baseline day. On a
      second day, a minimum of one week later, increasing concentrations (0.35, 115 and
      350 micrograms/ml) of latanoprost were added to the vehicle and given topically
      to both eyes. Healthy volunteers were given latanoprost only. ECG, blood
      pressure, heart rate, forced expiratory volume (FEV1), peak expiratory outflow
      (PEF) and forced vital capacity (FVC) were recorded immediately prior to and 15,
      30, 45 and 60 minutes after latanoprost. Asthmatic patients inhaled salbutamol
      (0.2 mg) at 60 minutes after the highest latanoprost dose. There were no
      significant differences in pulmonary function, blood pressure or heart rate after
      latanoprost in the healthy volunteers. Moreover, all parameters were unaffected
      in asthmatic patients on the day latanoprost was given compared to the baseline
      day. Latanoprost did not dampen the bronchodilator response to beta-2-adrenergic
      stimulation. It is concluded that latanoprost did not affect lung function in
      healthy subjects or in asthmatics after a total accumulated dose 10 times that
      clinically recommended for glaucoma treatment. Therefore, latanoprost appears to
      be safe for glaucoma treatment in patients with steroid-treated stable moderate
      intrinsic asthma.

PMID- 9154287
TI  - The color of the human eye: a review of morphologic correlates and of some
      conditions that affect iridial pigmentation.
AB  - Iris color can be affected by a variety of ocular disorders. It is suspected that
      iris color may not remain constant throughout life. These observations have drawn
      attention to the morphologic correlates of iris color and its regulation.
      Differences in the iris color of normal eyes are the result of variable amounts
      of melanin pigment granules within a constant number of melanocytes in the
      superficial stroma of the iris. These melanocytes seem to reach their genetically
      determined amount of melanin in early childhood, and their melanin content
      usually remains constant in adulthood. Diseases such as Horner's syndrome and
      Fuchs' heterochromic iridocyclitis affect iris color, resulting in a decrease of
      iris pigmentation. Evidence suggests that melanin content of some melanocytes is
      subject to adrenergic regulation even past childhood. Application of the
      prostaglandin analogue latanoprost, on the other hand, leads to an increase in
      iris pigmentation in some patients. Studies with cultured dermal and uveal
      melanocytes, as well as with uveal melanoma cells, however, show no increase in
      cell proliferation when treated with latanoprost in vitro. The mechanisms by
      which latanoprost affects regulation of iris pigmentation requires further
      investigation.

PMID- 9154288
TI  - Prostaglandin-induced iridial pigmentation in primates.
AB  - Latanoprost, a new ocular hypotensive prostaglandin F2 alpha analogue prodrug,
      was found to induce increased pigmentation of monkey irides in chronic toxicity
      studies. This prompted us to investigate the effect of naturally occurring
      prostaglandins on the monkey iris to determine whether this pigmentary effect is
      unique for latanoprost or whether it is a class effect of prostaglandins. PGF2
      alpha-isopropyl ester (IE), PGE2-IE and latanoprost were applied topically to
      cynomolgus monkey eyes for 18-44 weeks. One eye of each animal was treated, while
      the other served as control. In addition, latanoprost was applied to
      sympathectomized monkey eyes. PGF2 alpha-IE, PGE2-IE, as well as latanoprost,
      induced increased pigmentation in the monkey eye. The first signs of this effect
      were seen after about two months of treatment. Latanoprost also induced increased
      pigmentation in sympathectomized eyes. It is concluded that both naturally
      occurring prostaglandins and their synthetic analogues can induce increased
      iridial pigmentation in cynomolgus monkeys, and that the effect does not require
      the presence of sympathetic nerves.

PMID- 9154289
TI  - The incidence and time-course of latanoprost-induced iridial pigmentation as a
      function of eye color.
AB  - Latanoprost, a phenyl-substituted analogue of prostaglandin F2 alpha administered
      as eye drops, induces increased melanogenesis in the iridial melanocytes of
      monkeys. Similar effects were seen in 12, 23 and 11% of patients in the USA,
      United Kingdom (UK) and Scandinavia, respectively, during one year of treatment.
      The highest incidence of induced pigmentation was seen in green-brown, yellow
      brown and blue/grey-brown eyes, in that order. The relatively high proportion of
      patients with green-brown eyes in the UK explains the larger number of affected
      patients in this country. Typically, a concentric increase of the iris
      pigmentation appeared after six months (range: 3-17) and was judged to be
      noticeable by the patient in about 2/3 of the cases. After cessation of
      latanoprost, no change of the induced pigmentation has been seen in patients
      followed for two years, and there have been no signs of dispersion of pigment
      into the anterior chamber. Irides, homogeneously blue, grey, green or brown, were
      seldom affected. Naevi or freckles on iris, conjunctiva, or eye lids were not
      affected. It is intriguing that many patients with mixed eye color, particularly
      the blue-brown eyes, have not developed increased pigmentation even during two
      years of treatment. This could be due to a relatively slow melanogenesis or to
      refractory melanocytes in these individuals.

PMID- 9154290
TI  - Circadian intraocular pressure management with latanoprost: diurnal and nocturnal
      intraocular pressure reduction and increased uveoscleral outflow.
AB  - Based on their mechanism of action, the most frequently used ocular hypertensive
      agents, the beta-blockers, cannot be assumed to reduce IOP during sleep. The need
      for drugs that reduce IOP around-the-clock is underscored, however, by the fact
      that inadequate nocturnal ocular perfusion pressure is considered to be one of
      the likely causes of glaucomatous optic neuropathy especially in some cases of
      normal tension glaucoma. The studies reviewed here demonstrate that latanoprost,
      a new ocular hypotensive prostaglandin F2 alpha analogue, applied once a day at a
      concentration of 0.005%, maintains a statistically highly significant IOP
      reduction around-the-clock. The magnitude of this IOP reduction was found to be
      essentially identical during the day and at night, both in patients maintained on
      timolol and in those not receiving other glaucoma medication. Latanoprost-induced
      IOP reduction was also found to be associated with increased uveoscleral outflow
      in normotensive volunteers, both during the day and at night. These circadian
      studies suggest that this new ocular hypotensive agent can be expected to be
      particularly useful for the medical management of some forms of glaucoma, such as
      normal tension glaucoma, when the cause of the glaucomatous damage cannot be
      linked specifically to diurnal IOP abnormalities.

PMID- 9154291
TI  - Guidelines for audiology service delivery in nursing homes. Ad Hoc Committee on
      Audiology Service Delivery in Home Care and Institutional Settings. American
      Speech-Language-Hearing Association.
AB  - The increasing number of older adults in society as well as changing consumer
      preference and health care delivery systems have led to more frequent activity of
      audiologists in the delivery of services in nursing homes. The nursing home
      setting presents a number of challenges for the audiologist. It is anticipated
      that this document will provide audiologists with a comprehensive hearing
      management protocol and facilitate audiologists to confront the numerous
      challenges of the nursing home setting and provide quality audiology services.

PMID- 9154292
TI  - Herbert Pardes, MD.
AB  - Though mergers, affiliations, and financial challenges pervade all of academic
      medicine, New York City exhibits in microcosm the changes taking place throughout
      the country. At the helm of Columbia University College of Physicians and
      Surgeons is Herbert Pardes, MD, who came to Columbia in 1984 from the NIH and has
      served as dean since 1989. Since becoming dean, Pardes has received high marks
      for re-invigorating the academic strengths of Columbia while skillfully managing
      the financial issues faced by an inner-city medical center. Interviewed in his
      office in upper Manhattan, Pardes candidly discussed life and times in the big
      city and the difficulties of maintaining an emphasis on research in an era when
      money talks.

PMID- 9154293
TI  - A proposal for funding clinical research trials by health care insurers.

PMID- 9154294
TI  - Clinical spectrum and complications of the nephrotic syndrome.

PMID- 9154295
TI  - Conflict of interest and institutional review boards.

PMID- 9154296
TI  - Upregulation of interferon-alpha receptor expression in hydroxyurea-treated
      leukemia cell lines.
AB  - BACKGROUND: Interferon-alpha (IFN-alpha) shows its antitumor effect through
      binding to specific cell surface receptors. A DNA synthesis inhibitor,
      hydroxyurea (HU), has been successfully combined with IFN-alpha to improve the
      efficiency of IFN therapy for chronic myelogenous leukemia (CML). To understand
      the mechanism of this combination effect, expression of IFN-alpha receptors on
      the CML cell line, K562, was studied before and after treatment with HU. METHODS:
      Cells were treated with HU at a dose of 0, 0.1, 0.2, or 0.4 mmol/L for 48 hours.
      Binding assays were performed using 125I-labeled IFN-alpha at 4 degrees C. Cell
      cycle analysis was carried out using flow cytometer following staining cellular
      DNA with propidium iodide. Northern blot analysis was performed to evaluate the
      inducibility of interferon regulatory factor-1 (IRF-1) gene expression by IFN
      alpha. RESULTS: Hydroxyurea-treated cells showed a dose- and time-dependent
      increase in binding of 125I-labeled IFN-alpha (maximal 2.5-fold). The increase of
      binding was caused by an increase in the number of binding sites with a constant
      receptor affinity. Similar results were obtained in the Burkitt's lymphoma cell
      line, Daudi. Cell cycle analyses suggested that upregulation of the IFN receptor
      may have occurred as a result of the alteration in the cell cycle distribution.
      Furthermore, IFN-alpha induction of the IFN-inducible gene IRF-1 mRNA in HU
      treated K562 cells was 2-fold higher than that in untreated cells. CONCLUSIONS:
      Thus, HU may have an ability to enhance the response to IFN-alpha probably
      because of its ability to upregulate the IFN-alpha receptors, suggesting that
      this may be involved in the mechanism of effective combination therapy of IFN
      alpha with HU.

PMID- 9154297
TI  - Chlamydia species infect human vascular endothelial cells and induce procoagulant
      activity.
AB  - BACKGROUND: Chlamydia pneumoniae infections have been linked with myocardial
      infarction, stroke, and the development of atherosclerosis by epidemiologic
      studies, immunohistochemical studies, and electron microscopic studies. The
      mechanisms underlying this association are unknown. METHODS: Using cultured human
      venous endothelial cells, we investigated whether C pneumoniae, C trachomatis
      (types H and L2/434/BU) could infect these cells. The ability of infected cells
      to express procoagulant (tissue factor) activity was also measured using clotting
      and chromogenic substrate assays. Adhesion of platelets to chlamydia-infected
      cells was also quantitated. RESULTS: We found that C pneumoniae, C trachomatis
      type H, and C trachomatis L2/434/BU could infect cultured human umbilical vein
      endothelial cells and stimulate a 4-fold increase in expression of tissue factor,
      which reached a peak 18 hours postinfection. Tissue factor expression was
      enhanced even in the presence of tetracycline, suggesting that the chlamydial
      factor responsible for stimulating synthesis of endothelial cell tissue factor
      was preformed. Platelet adhesion was significantly enhanced when endothelial
      cells were infected by chlamydia species. CONCLUSIONS: These in vitro studies
      suggest possible pathogenic mechanisms that may explain the association of
      thrombotic events with C pneumoniae infection, including pathologically enhanced
      production of tissue factor by human endothelial cells and enhanced focal
      platelet deposition.

PMID- 9154298
TI  - Cytomegalovirus immediate early genes upregulate interleukin-6 gene expression.
AB  - BACKGROUND: The immediate early genes (IE) of human cytomegalovirus (CMV) can be
      expressed in monocytic cells and are known to regulate viral and cellular genes.
      Interleukin-6 (IL-6) plays a central role in numerous inflammatory and immune
      processes. Interleukin-6 levels are increased in lung transplant patients
      clinically diagnosed with CMV pneumonitis. The regulation of IL-6 is dependent on
      various stimuli that include lipopolysaccharide (LPS), viruses, and other
      cytokines. These studies examined the ability of CMV IE gene products to modulate
      IL-6 production. METHODS: THP-1 cells, a monocytic cell line, were transfected
      with the CMV IE genes. Interleukin-6 protein and IL-6 mRNA were measured in
      control and CMV immediate early transfected cells. Cotransfection of CMV IE genes
      and IL-6 chloramphenicol acetyl transferase (CAT) or IL-6 luciferase constructs
      were used to study IL-6 promoter activity. RESULTS: Interleukin-6 protein and
      mRNA production were significantly increased in cells transfected with the CMV IE
      genes and stimulated with LPS compared to LPS-stimulated control cells.
      Cytomegalovirus IE gene products significantly enhanced LPS stimulation of IL-6
      promoter activity in both IL-6 CAT and IL-6 luciferase assays. A deletion
      construct that contains a NF-kappa B site but is missing the multiple response
      region demonstrated a continued increase in IL-6 luciferase activity in LPS
      stimulated CMV transfected cells. CONCLUSION: Cytomegalovirus immediate early
      gene products significantly enhanced expression of IL-6 in LPS-stimulated cells.
      The increase in IL-6 luciferase activity occurs in the absence of the multiple
      response region, the area of the IL-6 promoter responsive to IL-1, TNF alpha,
      cyclic amp, and phorbol 12-myristate 13-acetate. The ability of CMV IE gene
      products to enhance IL-6 production may play an important role in immune
      inflammatory states associated with CMV infection.

PMID- 9154299
TI  - Mortality and length of stay as performance indicators for pneumonia in the
      elderly.
AB  - BACKGROUND: Mortality and length of stay are frequently used as performance
      measures for hospitals. If they are valid measures, they should be reproducible
      from year to year with attributable variation rather than random variation.
      METHODS: We compared hospitals on 2 outcomes, mortality and length of stay, in
      pneumonia in Medicare patients. The database was from 20 Illinois hospitals with
      the largest number of discharges for diagnosis-related group 89 (pneumonia with
      complications/comorbidities) for the years 1989 through 1992. This comprised
      16,249 claims for hospitalization in patients 65 years of age or older. RESULTS:
      The distributions showed trends toward lower mortality and shorter stays over the
      4 years. Correlation of performance from year to year at each hospital for
      mortality was low with none of the calculated correlation coefficients
      significant at p < .05. Correlations for length of stay were higher (all
      coefficients significant at p < .01). For length of stay, the correlation between
      1991 and 1992 was .766 (p < .00005, r2 = .587), showing that nearly 60% of
      differences (variance) were caused by differences in performance. In contrast,
      for mortality in 1991 and 1992, the correlation was .301 (p = .0986, r2 = .091),
      showing that less than 10% of differences (variance) between hospitals were
      caused by differences in performance. Similar results were obtained when the 20
      hospitals were ranked and their rank correlations calculated. CONCLUSION: For
      pneumonia in Medicare patients, differences in length of stay between hospitals
      are caused by differences in performance, while differences in mortality are
      random.

PMID- 9154300
TI  - Prognostic significance of beta-myosin heavy chain mutations is reflective of
      their hypertrophic expressivity in patients with hypertrophic cardiomyopathy.
AB  - BACKGROUND: Genotype-phenotype correlation studies consistently have shown that
      mutations are prognosticators in patients with hypertrophic cardiomyopathy (HCM).
      While Arginine (Arg)719Tryptophan (Trp) mutation in the beta-myosin heavy chain
      (MyHC) gene is associated with a high incidence of sudden cardiac death (SCD),
      the Valine (Val)606Methionine (Met) mutation in the same gene is associated with
      a near normal life expectancy. It is unknown whether the prognostic significance
      of mutations is reflective or independent of their hypertrophic expressivity. We
      determined the indices of left ventricular hypertrophy (LVH) in patients with
      beta-MyHC mutations associated with high, moderate, and low incidence of SCD.
      METHODS: Mutations were identified by chemical cleavage (Val606Met and Glu930Lys)
      or polymerase chain reaction (PCR) and MspI restriction mapping (Arg719Gln). Left
      ventricular mass was determined using 2-D echocardiograms, and was indexed (LVMI)
      for body surface area. The extent of LVH was determined using a semiquantitative
      point score method that takes into account the extent of involvement of the
      septum, apex, and lateral wall of the left ventricle. RESULTS: The Arg719Trp,
      Glu930Lys, and Val606Met mutations were associated with high (14/29, 48%),
      moderate (3/16, 19%), and low (1/11, 9%) risk of premature death, respectively.
      Concordant with the incidence of premature death, the LVMI was the greatest
      (148.0 +/- 37 g/m2) in patients with the Arg719Trp mutation, the smallest (111.7
      +/- 19 g/m2) in patients with the Val606Met mutation, and in between (127.1 +/-
      15 g/m2) in patients with the Glu930Lys mutation (p = 0.023). Similarly, the LVH
      score was also greater in patients with the Arg719Trp mutation than in those with
      the Val606Met mutation (5.92 +/- 2.3 vs 3.2 +/- 1.5, respectively, p = 0.015). A
      trend toward a greater septal thickness was also present in patients with the
      Arg719Trp compared to the Val606Met mutations (20.7 +/- 6.8 mm vs 16.2 +/- 2.6
      mm, p = 0.077). CONCLUSION: Hypertrophic cardiomyopathy patients with the
      malignant Arg719Trp mutation have more extensive hypertrophy than those with the
      benign Leu606Val mutation. This findings suggests that the prognostic
      significance of beta-MyHC mutations is reflective of their hypertrophic
      expressivity.

PMID- 9154301
TI  - 25th European Symposium on Calcified Tissues. Harrogate, United Kingdom, 25-29
      April 1997. Abstracts.

PMID- 9154302
TI  - Proceedings of the British Pharmacological Society Meeting. 18-20 December, 1996.

PMID- 9154304
TI  - [78th Congress of The Association of Anatomists. Madrid, Spain, 24-28 September
      1996. Abstracts].

PMID- 9154303
TI  - Membership list.

PMID- 9154305
TI  - British Diabetic Association's spring meeting and symposium on dyslipidaemia and
      the aetiology of non-insulin dependent diabetes. Harrogate, United Kingdom, 9-11
      April 1997. Abstracts.

PMID- 9154306
TI  - 11th European Cell Cycle Conference. Gardone Riviera, Italy, April 23-26, 1997.
      Abstracts.

PMID- 9154307
TI  - German Society for Experimental and Clinical Pharmacology and Toxicology 38th
      Spring Meeting. Mainz, Germany, 11-13 March 1997. Abstracts.

PMID- 9154308
TI  - Nuclear DNA content of fine needle aspirates of invasive ductal carcinomas of the
      breast.
AB  - Patients with aggressive breast cancers benefit from chemotherapy prior to
      surgery. If the biology of the breast cancers were better characterised pre
      operatively, more patients at risk could be offered chemotherapy. We have
      assessed nuclear DNA content of fine needle aspirates (FNA) of 103 invasive
      ductal breast cancers and compared this to tumour size, node status and
      histological grade. Median follow-up was 18 months so no prognostic studies were
      made. Diploid and non-diploid tumours were distributed equally in node negative
      and positive patients. However non-diploidy status increased in line with known
      prognostic markers of tumour size and histological grade. This suggests that
      ploidy might contribute to the pre-operative assessment of prognosis. We conclude
      that nuclear DNA of breast cancer FNAs may be of value in the pre-operative
      biological assessment of breast cancer patients.

PMID- 9154309
TI  - Dynamic changes in quantitative features of human gastric lesions.
AB  - Quantitative DNA, morphometric cellular and nuclear variables were evaluated in
      surgical biopsies from patients with various gastric lesions: chronic gastritis,
      chronic ulcers, adenomatous polyps (gastric adenomas), primary carcinomas and
      their corresponding lymph-node metastases. Paraffin-embedded tissue sections were
      studied by static cytophotometry (plug method), karyometry (measurements with a
      graduated eyepiece micrometer of the major and minor axes of the elliptic nuclear
      profiles, and calculation of profile areas), and measurements of cellular
      profiles (largest and smallest caliper diameters). Tissue lymphocytes from the
      same slide were used as diploid controls for the DNA evaluations. An increase of
      both cellular and nuclear dimensions and DNA content was noted in all
      pathological tissues, as compared to normal mucosa; the highest values are found
      in primary gastric carcinomas. A progressive pattern increase of cellular and
      nuclear dimensions and of DNA content was observed through normal to cancerous
      tissues, chronic gastritis, chronic ulcers and adenomatous polyps (adenomas).
      Lymph-node metastases, in our study, had smaller nuclear (cellular) dimensions
      than primary cancers.

PMID- 9154310
TI  - Relevance of chromatin features in the progression of esophageal epithelial
      severe dysplasia.
AB  - Since 1983, a long-term clinical trial of esophageal carcinoma chemoprevention
      has been conducted in a high-risk area in China. From this study, 25 esophageal
      severe dysplasia patients without therapy were selected for analysis. After 5
      year follow-ups, 14 cases progressed to esophageal carcinoma, while the other 11
      cases remained stable. Three Papanicolaou's smears were used for each case,
      including one from the esophageal cytological examination at the beginning, two
      from the re-examinations three and five years later respectively. About 100
      visually normal intermediate cells were randomly collected per slide by high
      resolution image analysis. More than 100 features (morphologic, densitometric,
      textural) were extracted. The classifications were made by means of stepwise
      linear discriminate analysis at the single cell level as on the specimen level
      using up to ten features. In all three comparisons of patients with progression
      and with regression at time of diagnosis, three years after diagnosis and five
      years later, the correct cell classification rates were about 70%. The subsequent
      specimen classifications by means of the a posteriori probability (APOP)
      distribution of the cells in each case led to 80% correct classification. All
      selected features reflected the chromatin structure of nuclei. The result
      demonstrated that the chromatin structures of esophageal epithelial cells in
      severely dysplasic patients are different between cases with and without
      progression. These results suggest the possibility of the application of image
      analysis in the clinical trials to find the dysplasia patients with higher risk
      of progression, in order to reduce the number of patients for therapy.

PMID- 9154311
TI  - Assessing slide coverage by cytoscreeners during the primary screening of
      cervical smears, using the AxioHOME Microscope system.
AB  - We have used the HOME Microscope system to examine the screening patterns of
      cytotechnologists who undertake the primary screening of cervical smears, in
      order to measure accuracy of screening against screening time, slide coverage,
      and mean screening rate. Twelve cytotechnologists engaged routinely on cervical
      screening volunteered for this study. They were asked to perform primary
      screening of 10 test slides under normal laboratory conditions in the normal way.
      Slide coverage and screening time were recorded on the HOME system. Slide maps
      were prepared and the results analysed. The exercise demonstrated that all
      primary screeners fail at some point to scan the whole of the slide during
      primary screening. The maps produced by the HOME system clearly demonstrated that
      5 different types of error can occur that lead to incomplete coverage of the
      slide. Mean slide coverage was 84%, and some individuals averaged only 66%
      coverage. The results show that there is a major problem in the education of some
      individual cytotechnologists in slide coverage. This could be rectified by the
      incorporation of a HOME system into every training centre, and the establishment
      of a protocol for assessment of slide coverage in competence examinations.
      Furthermore, the exercise has shown that even those individuals who normally
      attain a good standard of slide coverage would be able to improve slide coverage
      given access to the daily use of a HOME Microscope, or a system with equivalent
      screening/reviewing functionality.

PMID- 9154312
TI  - Limits of flow-cytometry histogram analysis methods to assess bladder tumour
      antigen expression.
AB  - Tumour-associated antigens detected in cells obtained from bladder washings or
      tumours are useful markers in bladder cancer. Flow cytometry is commonly used to
      quantify immuno-stained cells. A straightforward way to analyze data is to count
      the fluorescent cells above a threshold empirically determined on a control
      histogram representation. However, specific antigens expressed at highly variable
      rates give rise to wide range distributions in flow cytometry as illustrated when
      a mucin antigen for urinary bladder was titrated by M344 monoclonal antibody in
      urothelial cancer cells. We have evaluated several methods of background
      estimation and subtraction in order to determine the proportion of M344 Mab
      positive cells. These include threshold setting (Histogram Shape Dependent (HSD)
      threshold developed in this study, 2% preset or 5% preset background),
      subtraction of the blank from the test histograms, and Kolmogorov-Smirnov
      statistical test. The HSD method appeared to be a more reliable method for
      background estimation; however, in the case of very low antigen expression, where
      specific fluorescence histograms could hardly be distinguished from that of the
      background, fluorescence microscopy remained the only valid method, since it
      allowed the distinction between specific and non-specific fluorescence on the
      basis of structural differences between the two.

PMID- 9154313
TI  - The evolution of megakaryocytes to platelets.
AB  - Megakaryocytes (MKs) arise from pluripotent stem cells by a process of cell
      division, endoreplication and maturation. Progressively, the MK cytoplasm is
      invaded by the demarcation membrane system speculated to delimit pre-formed
      platelets. One theory is that the passage of entire MKs (or fragments) into the
      blood stream is followed by their physical break-up into platelets in the
      pulmonary circulation. A second theory is that MKs produce beaded processes
      (proplatelets) which then separate into platelets. Functionally vital platelet
      receptors such as GPIIb-IIIa and GPIb-IX complexes are specific markers of the MK
      lineage. CD34 and CD4 are present in progenitors but progressively disappear as
      MKs mature. Stroma cells secrete cytokines, produce extracellular matrix proteins
      and mediate cellular contact interactions that regulate MK development. Studies
      on thrombopoietin and the use of transgenic mouse models are helping to clarify
      MK biology.

PMID- 9154314
TI  - Positive and negative regulation of megakaryocytopoiesis.
AB  - The recently cloned physiological regulator of megakaryocytopoiesis, known as Mpl
      ligand, thrombopoietin (TPO), megakaryocyte growth and development factor (MGDF)
      or megapoietin, is undergoing preclinical and clinical trials. This factor is an
      extremely potent thrombocytopoietic agent in vivo in normal animals, and
      accelerates platelet recovery in some but not all models of myelosuppression.
      Together with its apparent lack of adverse effects, the preclinical data suggest
      that TPO might permit the use of higher doses of chemotherapy in dose-intensive
      regimens and be useful in patients with ineffective platelet production or
      production abnormalities. The direct effects of TPO on primitive and various
      myeloid committed haematopoietic progenitor cells predict that TPO may be used in
      combination with other cytokines in a variety of clinical disorders. Along with
      the progress made in the understanding of the positive regulation of
      megakaryocytopoiesis, accumulating data demonstrate that platelet production is
      also controlled by negative regulators with potential clinical applications. Some
      of these regulators are effective in the treatment of essential thrombocythaemia
      and myeloproliferative disorders, while others seem capable of protecting
      progenitor cells from the cytotoxicity of chemotherapeutic drugs.

PMID- 9154315
TI  - Megakaryocytic cell lines.
AB  - Megakaryocytic cell lines, established from the blood of patients with leukaemia,
      provide us with a unique opportunity to study the proliferation, differentiation
      and maturation of megakaryocytes. Eighteen human and three animal cell lines that
      express some megakaryocytic features have been described in the literature. Many
      of these cell lines have primitive multiphenotypic properties of erythroid,
      myeloid and megakaryocytic cells, while some show more restricted megakaryocyte
      specific markers. The most consistent cell marker of megakaryocytic cell lines is
      the presence of platelet membrane glycoprotein (GPIIb-IIIa) in human cell lines
      and that of acetylcholinesterase in mouse or rat cell lines. The expressions of
      GPIb, von Willebrand factor and platelet peroxidase are variable among different
      cell lines, perhaps reflecting different stages of differentiation or a
      neoplastic nature of immortal cell lines. Treatment of many of these cell lines
      with phorbol esters leads to enhanced expression of the megakaryocytic programme.

PMID- 9154316
TI  - Megakaryocytes and platelets in myeloproliferative disorders.
AB  - Increased megakaryocyte (MK) proliferation in bone marrow is a feature common to
      the three Ph-negative myeloproliferative disorders (MPDs), i.e. essential
      thrombocythaemia (ET), polycythaemia vera (PV), and myelofibrosis with splenic
      myeloid metaplasia (MMM), and to chronic myelocytic leukaemia (CML). Enlarged MKs
      with multilobulated nuclei and cell clustering in close proximity are the
      hallmark of all the Ph negative MPDs. Clonality of haematopoietic cells, based on
      X chromosome inactivation, can now be studied in a majority of female patients in
      all nucleated cell fractions as well as in platelets. Cytofluorometric studies
      have demonstrated a shift towards higher ploidy classes in PV and ET MKs which
      may be useful in discriminating between both primary and reactive thrombocytosis
      and CML patients which show a significant shift to lower MK ploidy values. The
      role of MK proliferation on the evolution of myelofibrosis common to MPDs has
      been firmly established. Implication of platelet-derived growth factor (PDGF) in
      myelofibrosis has already been demonstrated. More recently transforming growth
      factor beta (TGF beta) synthesized and secreted by MK has been implicated in
      fibroblasts stimulation. A significant increase in circulating colony-forming
      units of MKs (CFU-MK) has been repeatedly observed in MPDs as well as a
      spontaneous MK colony formation in a majority of ET patients. Hypersensitivity to
      thrombopoietin (TPO) in relation to a functional defect of the TPO-MPL pathway
      may play a major role in spontaneous MK growth. There is no currently available
      test of platelet functions able to predict the risk of occurrence of thrombotic
      or haemorrhagic complications in MPD patients. However, the role of platelet
      activation in the pathogenesis of ischaemic erythromelalgia has been established
      and a correlation between presenting haemorrhagic manifestations and platelet
      counts in excess of 1000 x 10(9)/l has been found.

PMID- 9154317
TI  - Megakaryocytes and platelets in immune thrombocytopenic purpura.
AB  - In idiopathic thrombocytopenic purpura, 90% of the patients have an elevated
      platelet-associated immunoglobulin. The most important related antigens are
      glycoprotein IIb-IIIa (GPIIb-IIIa) (16.7-83.3%), GPIb-IX (13.3-83%), GPIb (3.3
      47.1%) and GPIIIa (21.6-33.3%), and less commonly GPIa-IIa, GPIV and GPV. Other
      related antigens can be platelet granule membrane protein, phospholipid,
      intraplatelet and cytoplasmic antigens, and rarely human platelet antigen (HPA)
      1a and HLA-DR antigens. The marrow megakaryocytes are usually normal or increased
      in number with maturation impairment. There are discrepancies regarding
      megakaryocytopoiesis in vitro. A low dose of heparin could elevate the platelet
      number in certain cases. The expression of c-sis was reported to be inhibited in
      ITP, when the plasma beta-thromboglobin-platelet factor 4 level was elevated. In
      secondary immune thrombocytopenia, platelet antibodies can be (1) alloantibodies
      against the (HPA) system and (2) autoantibodies most commonly against platelet
      GPIIb-IIIa or GPIb-IX. Other antigens can be 30-52kDa proteins of the platelet
      membrane. Platelet survival is usually shortened, and marrow megakaryocytes are
      normal in number. Megakaryocyte colony-forming units could be reduced.

PMID- 9154318
TI  - Megakaryocytes and platelets in vascular disease.
AB  - Platelets are anucleate cells with no DNA. They are derived from their precursor,
      the megakaryocyte (MK), whose differentiation is characterized by nuclear
      polyploidization through a process called endomitosis. Changes in the MK-platelet
      haemostasis axis may precede acute thrombotic events. Changes in MK ploidy
      distribution may be associated with the production of large platelets. Mean
      platelet volume (MPV) is an important biological variable as it is a determinant
      of platelet reactivity. Large platelets are denser and more active
      haemostatically. MPV is increased in patients after myocardial infarction (MI)
      and is a predictor of a further ischaemic event and death when measured after MI.
      It has been suggested that changes not only in platelets but also in the parental
      MK are associated with chronic and acute vascular events. The regulation of
      megakaryocytopoiesis depends on several haematopoietic factors such as
      thrombopoietin. An understanding of the signalling system that controls platelet
      number and size might give insight into a role of platelet production in
      thrombogenesis and atherogenesis.

PMID- 9154319
TI  - Megakaryocytes and platelets in alpha-granule disorders.
AB  - This chapter summarizes research data contributing to current understanding of
      disorders affecting alpha-granules of megakaryocytes and platelets. Diagnostic
      features of the gray platelet syndrome are well defined. Combined evidence
      suggests a defect, specific to the megakaryocyte cell lineage, causing a
      cytoskeletal abnormality and defective targeting of endogenously synthesized
      proteins to the alpha-granule. The abnormalities linked by signal transduction
      pathways. von Willebrand disease and afibrinogenaemia are disorders which
      highlight the functional importance of platelet storage pools of von Willebrand
      factor and fibrinogen, essential ligands in the process of adhesion and
      aggregation. The abnormality in the factor V Quebec disorder leads to a
      degradation of most proteins contained within the alpha-granule. The familial
      platelet disorder Paris-Trousseau thrombocytopenia is the only alpha-granule
      disorder associated with a cytogenetic abnormality, and it presents a useful
      model for exploring the genetic influence on regulation of thrombopoiesis. Study
      of these syndromes has elucidated aspects of the physiology of normal
      megakaryocyte maturation and platelet formation, including storage organelle
      biosynthesis.

PMID- 9154320
TI  - Megakaryocytes and inherited thrombocytopenias.
AB  - Inherited thrombocytopenias may be divided into two groups. In the first group,
      there is no marked thrombocytopathy. Although numerous in the bone marrow,
      megakaryocytes often are abnormal cytologically. A dysmegakaryocytopoiesis with
      defective platelet production is suggested but remains to be evidenced. In the
      second group, thrombocytopenias are accompanied with variable thrombocytopathy.
      The functional and biochemical platelet abnormalities responsible for these
      different thrombocytopathies often are well elucidated. The study of the
      relations with the occurrence of thrombocytopenia constitutes an interesting
      field of investigation.

PMID- 9154321
TI  - Anti-platelet drugs: do they affect megakaryocytes?
AB  - Anti-platelet drugs are used in clinical medicine to prevent thromboembolic
      complications of cardiovascular diseases. Among anti-platelet drugs, very little
      is known of their possible effects on megakaryocytes. ASA is the only compound
      for which it has clearly been demonstrated that its mechanism of action involves
      acetylation of the Ser 529 residue in cyclo-oxygenase in platelets and
      megakaryocytes. Because megakaryocytes possess membrane receptors for ADP, the
      thienopyridine metabolites of ticlopidine and clopidogrel may modify these
      receptors as in platelets and hence prevent ADP binding and further activation.
      Megakaryocytes also have GPIIb-IIIa receptors for the adhesive protein fibrinogen
      and may be accessible in vivo to GPIIb-IIIa antagonists such as the monoclonal
      antibody abciximab. Drugs such as heparin or the phosphodiesterase inhibitor
      anagrelide can either inhibit or stimulate megakaryocytopoiesis and platelet
      production, while cytokines such as thrombopoietin affect megakaryocytopoiesis,
      platelet production and platelet function by potentiating the activation of
      platelets by other agonists.

PMID- 9154322
TI  - Receptor specificity and trigemino-vascular inhibitory actions of a novel 5
      HT1B/1D receptor partial agonist, 311C90 (zolmitriptan).
AB  - 1. 311C90 (zolmitriptan zomig: (S)-4[[3-[2-(dimethylamino)ethyl]-1H-indol-5
      yl]methyl]-2-oxazolidinone) is a novel 5-HT1B/1D receptor agonist with proven
      efficacy in the acute treatment of migraine. Here, we describe the receptor
      specificity of the drug and its actions on trigeminal-evoked plasma protein
      extravasation into the dura mater of the anaesthetized guinea-pig. 2. At the "5
      HT1B-like' receptor mediating vascular contraction (rabbit saphenous vein), the
      compound was a potent (p[A50] = 6.79 +/- 0.06) partial agonist achieving 77 +/-
      4% of the maximum effect to 5-hydroxytryptamine (5-HT). In the same experiments,
      sumatriptan (p[A50] = 6.48 +/- 0.04) was half as potent as 311C90 and produced 97
      +/- 2% of the 5-HT maximum effect. Studies in which receptor inactivation methods
      were used to estimate the affinity (pKA) and efficacy relative to 5-HT (tau rel)
      for each agonist confirmed that 311C90 exhibits higher affinity than sumatriptan
      (pKA = 6.63 +/- 0.04 and 6.16 +/- 0.03, respectively) and that both drugs are
      partial agonists relative to 5-HT (tau rel = 0.61 +/- 0.03 and 0.63 +/- 0.10,
      respectively, compared to 5-HT = 1.0). 3. Consistent with its effects in rabbit
      saphenous vein, 311C90 also produced concentration-dependent contractions of
      primate basilar artery and human epicardial coronary artery rings. In basilar
      artery, agonist potency (p[A50] = 6.92 +/- 0.07) was similar to that demonstrated
      in rabbit saphenous vein, again being 2-3 fold higher than for sumatriptan
      (p[A50] = 6.46 +/- 0.03). Both agonists produced about 50% of the maximum
      response obtained with 5-HT in the same preparations. In rings of human coronary
      artery, the absolute potency of 311C90 and sumatriptan was higher than in primate
      basilar artery (p[A50] = 7.3 +/- 0.1 and 6.7 +/- 0.1, respectively), but maximum
      effects relative to 5-HT were lower (37 +/- 8% and 35 +/- 7%, respectively). In
      both types of vessel, the inability of 5-HT1B/1D agonists to achieve the same
      maximum as the endogenous agonist 5-HT is explained by the additional presence of
      5-HT2A receptors. 4. 311C90 displayed high affinity at human recombinant 5-HT1D
      (formerly 5-HT1D alpha) and 5-HT1B (formerly 5-HT1D beta) receptors in
      transfected CHO-K1 cell membranes (pIC50 values = 9.16 +/- 0.12 and 8.32 +/-
      0.09, respectively). In intact cells, the drug produced concentration-dependent
      inhibition of forskolin-stimulated adenylyl cyclase (p[A50] = 9.9 and 9.5,
      respectively) achieving the same maximum effect as 5-HT. Excepting human
      recombinant 5-HT1A and 5-ht1F receptors at which the drug behaved as an agonist
      with modest affinity (pIC50 = 6.45 +/- 0.11 and 7.22 +/- 0.12, respectively),
      311C90 exhibited low, or no detectable affinity (pKi or pKB < or = 5.5) at
      numerous other monoamine receptors, including other 5-HT receptor subtypes. 5.
      When administered to anaesthetized guinea-pigs ten minutes before unilateral
      electrical stimulation of the trigeminal ganglion (1.2 mA, 5 Hz, 5 ms, 5 min),
      311C90 (3-30 micrograms kg-1, i.v.) caused a dose-dependent inhibition of [125I]
      albumin extravasation within the ipsilateral dura mater. At the same doses, the
      drug also produced dose-dependent falls in cranial vascular conductance (32.3 +/-
      7.5% at 30 micrograms kg-1), as measured in the ear by laser doppler flowmetry.
      6. These results show that 311C90, a novel member of the 5-HT1B/1D agonist drug
      class, exhibits a high degree of pharmacological specificity. Its potent partial
      agonist action at "5-HT1B-like' receptors in intracranial arteries, coupled with
      potent agonism at 5-HT1D and 5-HT1B receptors and an ability to inhibit
      neurogenic plasma protein extravasation in the dura, are consistent with its
      utility as an effective acute treatment for migraine.

PMID- 9154323
TI  - Central antitussive activity of the NK1 and NK2 tachykinin receptor antagonists,
      CP-99,994 and SR 48968, in the guinea-pig and cat.
AB  - 1. The purpose of this study was to investigate the antitussive activity and
      sites of action of the NK1 and NK2 tachykinin receptor antagonists, CP-99,994, SR
      48968, and the racemate of SR 48968, SR 48212A in the cat and guinea-pig. 2.
      Guinea-pigs were dosed subcutaneously (s.c.) with CP-99,994, SR 48212A or SR
      48968 one hour before exposure to aerosols of capsaicin (0.3 mM) to elicit
      coughing. Coughs were detected with a microphone and counted. 3.
      Intracerebroventricular (i.c.v.) cannulae were placed in the lateral cerebral
      ventricles of anaesthetized guinea-pigs. Approximately one week later, the
      animals were dosed with CP-99,994 or SR 48212A (i.c.v.) and exposed to aerosols
      of capsaicin (0.3 mM) to elicit coughing. 4. Cough was produced in anaesthetized
      cats by mechanical stimulation of the intrathoracic trachea and was monitored
      from electromyograms of respiratory muscle activity. Cannulae were placed for
      intravenous (i.v.) or, in separate groups of animals, intravertebral arterial
      (i.a.) administration of CP-99,994, SR 48212A or SR 48968. Dose-response
      relationships for i.v. and i.a. administration of each drug were generated to
      determine a ratio of i.v. ED50 to i.a. ED50, known as the effective dose ratio
      (EDR). The EDR will be 20 or greater for a centrally active drug and less than 20
      for a peripherally active drug. 5. In the guinea-pig, CP-99,994 (0.1-30 mg kg-1,
      s.c.), SR 48212A (1.0-30 mg kg-1, s.c.), and SR 48968 (0.3-3.0 mg kg-1, s.c.)
      inhibited capsaicin-induced cough in a dose-dependent manner. Capsaicin-induced
      cough was also inhibited by i.c.v. administration of CP-99,994 (10 and 100
      micrograms) or SR 48212A (100 micrograms). 6. In the cat, both CP-99,994 (0.0001
      0.3 mg kg-1, i.a., n = 5; 0.003-3.0 mg kg-1, i.v., n = 5) and SR 48212A (0.003
      1.0 mg kg-1, i.a., n = 5; 0.01-3.0 mg kg-1, i.v., n = 5) inhibited mechanically
      induced cough by either the i.v. or i.a. routes in a dose-dependent manner. SR
      48968 (0.001-0.3 mg kg-1, i.a., n = 5; 0.03-1.0 mg kg-1, i.v., n = 5) inhibited
      cough when administered by the i.a. route in a dose-dependent manner, but had no
      effect by the i.v. route up to a dose of 1.0 mg kg-1. Intravenous antitussive
      potencies (ED50, 95% confidence interval (CI) of these compounds were: CP-99,994
      (0.082 mg kg-1, 95% CI 0.047-0.126), SR 48212A (2.3 mg kg-1, 95% CI 0.5-20), and
      SR 48968 (> 1.0 mg kg-1, 95% CI not determined). The intra-arterial potencies of
      these compounds were: CP-99,994 (1.0 microgram kg-1, 95% CI 0.4-1.8), SR 48212A
      (25 micrograms kg-1, 95% CI 13-52), and SR 48968 (8.0 micrograms kg-1, 95% CI 1
      32). The derived EDRs for each compound were: CP-99,994, 82; SR 48212A, 92; and
      SR 48968, > 125. 7. We concluded that CP-99,994 and SR 48968 inhibit cough in the
      guinea-pig and cat by a central site of action. In the cat, the antitussive
      action of these compounds appears to be solely by a central site.

PMID- 9154324
TI  - Selective induction of cyclo-oxygenase-2 activity in the permanent human
      endothelial cell line HUV-EC-C: biochemical and pharmacological characterization.
AB  - 1. Cyclo-oxygenase (COX), the enzyme responsible for the conversion of
      arachidonic acid (AA) to prostaglandin H2 (PGH2), exists in two forms, termed COX
      1 and COX-2 which are encoded by different genes. COX-1 is expressed
      constitutively and is known to be the site of action of aspirin and other
      nonsteroidal anti-inflammatory drugs. COX-2 may be induced by a series of pro
      inflammatory stimuli and its role in the development of inflammation has been
      claimed. 2. Endothelial cells are an important physiological source of
      prostanoids and the selective induction of COX-2 activity has been described for
      finite cultures of endothelial cells, but not for permanent endothelial cell
      lines. 3. The HUV-EC-C line is a permanent endothelial cell line of human origin.
      We have determined the COX activity of these cells under basal conditions and
      after its exposure to two different stimuli, phorbol 12-myristate 13-acetate
      (PMA) and interleukin-1 beta (IL-1 beta). 4. Both PMA and IL-1 beta produced dose
      and time-dependent increases of the synthesis of the COX-derived eicosanoids.
      These increases were maximal after the treatment with 10 nM PMA for 6 to 9 h.
      Under these conditions, the main eicosanoid produced by the cells was PGE2. 5.
      The increase of COX activity by PMA or IL-1 beta correlated with an increase of
      the enzyme's apparent Vmax, whilst the affinity for the substrate, measured as
      apparent Km, remained unaffected. 6. Treatment of the cells with PMA induced a
      time-dependent increase in the expression of both COX-1 and COX-2 mRNAs.
      Nevertheless, this increase was reflected only as an increase of the COX-2
      isoenzyme at the protein level. 7. The enzymatic activity of the PMA-induced COX
      was measured in the presence of a panel of enzyme inhibitors, and the IC50 values
      obtained were compared with those obtained for the inhibition of human platelet
      COX activity, a COX-1 selective assay. Classical non-steroidal anti-inflammatory
      drugs (NSAIDs) inhibited both enzymes with varying potencies but only the three
      compounds previously shown to be selective COX-2 inhibitors (SC-58125, NS-398 and
      nimesulide) showed higher potency towards the COX of PMA-treated HUV-EC-C. 8.
      Overall, it appears that the stimulation of the HUV-EC-C line with PMA
      selectively induces the COX-2 isoenzyme. This appears to be a suitable model for
      the study of the physiology and pharmacology of this important isoenzyme, with a
      permanent endothelial cell line of human origin.

PMID- 9154325
TI  - The effect of okadaic acid on non-adrenergic non-cholinergic contraction in
      guinea-pig isolated bronchus.
AB  - 1. We have investigated the role of phosphatases in modulating contractile
      responses to electrical field stimulation (EFS), methacholine, substance P and
      capsaicin in guinea-pig isolated main bronchus by use of the phosphatase 1 and 2A
      inhibitor okadaic acid. 2. Non-adrenergic non-cholinergic (eNANC) contractile
      responses were elicited by EFS (3 Hz, 20 s, 0.5 ms max. voltage) in the guinea
      pig isolated main bronchus in the presence of the non-selective muscarinic
      antagonist, atropine (1 microM), the non-selective beta-adrenoceptor antagonist;
      propranolol (1 microM), the neutral endopeptidase inhibitor thiorphan (10 microM)
      and the cyclo-oxygenase inhibitor, indomethacin (5 microM). Okadaic acid
      significantly attenuated eNANC contractile responses (% inhibition) elicited by
      EFS (0.01 microM, 15.2 +/- 26.9%; 0.03 microM, 30.4 +/- 13.9%; 0.01 microM, 39.8
      +/- 5.1%; 0.3 microM, 59.5 +/- 8.7%; 1 microM 77.8 +/- 7.8%; P < 0.05, n = 4). In
      contrast, the inactive analogue 1-Nor okadaone (0.3 microM) failed to attenuate
      significantly eNANC contractile responses (% inhibition elicited by 1-Nor
      okadaone, -1.25 +/- 8.5% vs dimethylsulphoxide (DMSO), -13.5 +/- 21.5%; P > 0.05,
      n = 4). 3. Cholinergic contractile responses were elicited by EFS (1-30 Hz, 10 s,
      0.5 ms max. voltage) in guinea-pig isolated bronchus in the presence of the
      nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME,
      30 microM). Okadaic acid failed to attenuate significantly the contractile (%
      methacholine Emax) response elicited by EFS at all frequencies tested compared
      with the control (1 Hz, control, 22 +/- 7.9% vs okadaic acid, 18 +/- 7.7%; 3 Hz,
      control, 26 +/- 6.9% vs okadaic acid, 27 +/- 9.1%; 10 Hz, control, 36 +/- 7.6% vs
      okadaic acid, 33 +/- 8.9%; 30 Hz, control, 50 +/- 7.6% vs okadaic acid, 42 +/-
      14%; P > 0.05, n = 4). 4. Okadaic acid (0.3 microM) failed to alter significantly
      the contractile potency (pD2) to capsaicin (okadaic acid, 9.0 +/- 0.5, vs DMSO,
      9.2 +/- 0.4; P > 0.05 n = 6), substance P (okadaic acid, 7.6 +/- 0.3 vs DMSO, 8.2
      +/- 0.2; P > 0.05 n = 7) or methacholine (okadaic acid, 6.4 +/- 0.2 vs DMSO, 6.4
      +/- 0.3; P > 0.05 n = 4). 5. Okadaic acid (0.01-1 microM) did not appear to
      reverse substance P-induced tone. The maximal relaxant response (% reversal of
      substance P-induced tone) mediated by okadaic acid (1 microM) was 33 +/- 11.7% (n
      = 4), this was not significantly different from the DMSO (0.8%) or a time
      dependent fall in tone of 34.3 +/- 23.1% (n = 4) and 33 +/- 15.8% (n = 4),
      respectively. Okadaic acid (0.3 microM) failed to augment isoprenaline-induced
      relaxation responses in substance P contracted bronchus (okadaic acid, 6.5 +/-
      0.4 vs DMSO, 5.9 +/- 0.3; P > 0.05, n = 9). 6. These results indicate that
      protein phosphatases appear to regulate the release of sensory neuropeptides from
      airway sensory nerves in response to electrical field stimulation.

PMID- 9154326
TI  - NO-dependent and NO-independent IL-1 production by a human colonic epithelial
      cell line under inflammatory stress.
AB  - 1. The present study was designed to investigate, in an in vitro model of the
      human intestinal barrier, the ability of epithelial cells to produce interleukin
      1 (IL-1), the cellular mechanisms involved in IL-1 release, and the intracellular
      signalling pathways involved in IL-1 up-regulation during inflammatory stress. 2.
      This study was based on the human colonic epithelial cell line HT29-Cl.16E,
      maintained as polarized monolayers on filters mounted in culture chambers and
      treated with various proinflammatory cytokines (interferon gamma (IFN gamma),
      tumour necrosis factor alpha (TNF alpha), IL-1 beta) alone or in combination. 3.
      IL-1 production, restricted to IL-1 alpha, was induced by the combination of IFN
      gamma/TNF alpha. When IL-1 beta was added to IFN gamma/TNF alpha, it led to an
      additional production of IL-1 alpha. IL-1 alpha release was associated with cell
      damage, as shown by the correlation between lactate dehydrogenase (LDH) release
      and extracellular IL-1 production, and was not accounted for by a secretory
      mechanism. 4. Both IFN gamma/TNF alpha and IFN gamma/TNF alpha/IL-1 beta induced
      inducible nitric oxide synthase (iNOS) expression as shown by quantitation of NO2
      /NO3- by use of the Griess reagent, quantitation of cells scoring positive with
      an anti-iNOS antibody and detection of mRNAs coding for iNOS by RT-PCR. The use
      of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NOS, led to the
      demonstration of two distinct signalling pathways in IL-1 production by HT29
      Cl.16E cells, one dependent on NO (L-NMMA-sensitive) under treatment with IFN
      gamma/TNF alpha/IL-1 beta, and the other independent of NO (L-NMMA-insensitive)
      under treatment with IFN gamma/TNF alpha. 5. Moreover, we examined whether a
      redox-based mechanism could be responsible for the apparent discrepancy between
      NO production and NO implication in IL-1 production under IFN gamma/TNF alpha and
      IFN gamma/TNF alpha/IL-1 beta treatments. Experiments with cysteine, which acts
      as a powerful reductant, suggest that the nitrosonium character of NO is involved
      in the NO-dependent pathway in IL-1 production.

PMID- 9154327
TI  - KATP-channel on the somata of spiny neurones in rat caudate nucleus: regulation
      by drugs and nucleotides.
AB  - 1. The aim of the present study was to characterize the pharmacological
      properties of the adenosine 5'-triphosphate(ATP)-sensitive K+ channel (KATP
      channel) on the somata of spiny neurones in rat caudate nucleus and to compare
      them with those of beta-cells. For that purpose we tested the effects of several
      KATP-channel-inhibiting and -activating drugs on the opening activity of the KATP
      channel in caudate nucleus by use of the patch-clamp technique. In addition, the
      modulation of drug responses by cytosolic nucleotides was examined. 2. When KATP
      channels in caudate nucleus were activated in cell-attached patches by inhibition
      of mitochondrial energy production, meglitinide (a benzoic acid derivative),
      Hoe36320 (a sulphonylurea of low lipophilicity) and glipizide reduced KATP
      channel activity half-maximally at 0.4 microM, 0.4 microM and about 0.5 nM,
      respectively. 3. In inside-out patches (presence of 0.7 mM free Mg2+ at the
      cytoplasmic membrane side), tolbutamide (0.1 mM) caused only partial inhibition
      of KATP-channels in the absence of cytosolic nucleotides but complete inhibition
      in the simultaneous presence of the channel-activating nucleotide guanosine 5'
      diphosphate (GDP; 1 mM) and the channel-inhibiting nucleotide adenylyl
      imidodiphosphate (AMP-PNP; 0.2 mM). 4. Diazoxide (0.3 mM) strongly increased
      channel activity in the presence of ATP (0.1 mM) or GDP (0.03 mM), but was
      ineffective in the presence of AMP-PNP (0.1 mM). In the absence of cytosolic
      nucleotides diazoxide even decreased channel activity. 5. In the presence of 0.1
      mM ATP, diazoxide activated KATP-channels half-maximally at 38 microM. 6. When
      KATP-channel activity was inhibited by 0.1 mM ATP, (-)-pinacidil (0.5 mM)
      elicited a slight activation of KATP-channels in caudate nucleus, whereas (+)
      pinacidil (0.5 mM) and lemakalim (0.3 mM) were ineffective. 7. Since our data
      indicate similar control by drugs and nucleotides of KATP-channels in the somata
      of spiny neurones and pancreatic beta-cells, we conclude that the high affinity
      sulphonylurea receptors of these tissues are probably closely related.

PMID- 9154328
TI  - Effects of hypomagnesia on histamine H1 receptor-mediated facilitation of NMDA
      responses.
AB  - 1. The ability of histamine to facilitate the N-methyl-D-aspartate (NMDA) induced
      depolarization of cortical projection neurones was examined by use of grease-gap
      recording. 2. Histamine (1 to 15 microM) reversibly facilitated the NMDA-induced
      depolarization yielding a bellshaped concentration-response relationship. The
      peak enhancement was 167% above the control at 10 microM histamine.
      Desensitization was present in 4 out of 5 slices on second exposure 40 min
      following the first exposure. 3. Histamine did not alter the depolarization
      induced by 10 microM kainate. 4. The histamine-induced facilitation persisted in
      the presence of tetrodotoxin, but was reduced in a concentration-dependent manner
      by diphenhydramine (IC50 = 7.6 nM). Cyproheptadine (10 nM) also reduced the
      facilitation, whereas ranitidine (200 nM) and thioperamide (10 nM) were
      ineffective in this regard. 5. Histamine (10 microM) facilitated the NMDA (25
      microM)-induced depolarization in nominally Mg(2+)-free medium. The magnitude of
      the facilitation was smaller than that observed in Mg(2+)-containing medium (17%
      above the control) and desensitization was not observed. This facilitation was
      not reduced by cyproheptadine (10 nM) or diphenhydramine (1 microM). 6. We
      conclude that histamine facilitates the NMDA depolarization at cortical neurones
      via two distinct mechanisms. One mechanism involves activation of the histamine
      H1 receptor and is sensitive to Mg2+. The second mechanism is independent of
      histamine cell surface receptor activation and may reflect a direct action of
      histamine at the NMDA receptor.

PMID- 9154329
TI  - Induction by low Na+ or Cl- of cocaine sensitive carrier-mediated efflux of
      amines from cells transfected with the cloned human catecholamine transporters.
AB  - 1. COS-7 cells transfected with the cDNA of the human dopamine transporter (DAT
      cells) or the human noradrenaline transporter (NAT cells) were loaded with [3H]
      dopamine or [3H]-noradrenaline and superfused with buffers of different ionic
      composition. 2. In DAT cells lowering the Na+ concentration to 0, 5 or 10 mM
      caused an increase in 3H-efflux. Cocaine (10 microM) or mazindol (0.3 microM)
      blocked the efflux at low Na+, but not at 0 Na+. Lowering the Cl- concentration
      to 0, 5 or 10 mM resulted in an increased efflux, which was blocked by cocaine or
      mazindol. Desipramine (0.1 microM) was without effect in all the conditions
      tested. 3. In NAT cells, lowering the Na+ concentration to 0, 5 or 10 mM caused
      an increase in 3H-efflux, which was blocked by cocaine or mazindol. Desipramine
      produced a partial block, its action being stronger at 5 or 10 mM Na+ than at 0
      mM Na+. Efflux induced by 0, 5 or 10 mM Cl- was completely blocked by all three
      uptake inhibitors. 4. In cross-loading experiments, 5 mM Na(+)- or 0 Cl(-)
      induced efflux was much lower from [3H]-noradrenaline-loaded DAT, than NAT cells
      and was sensitive to mazindol, but not to desipramine. Efflux from [3H]-dopamine
      loaded NAT cells elicited by 5 mM Na+ or 0 Cl- was blocked by mazindol, as well
      as by desipramine. 5. Thus cloned catecholamine transporters display carrier
      mediated efflux of amines if challenged by lowering the extracellular Na+ or Cl-,
      whilst retaining their pharmacological profile. The transporters differ with
      regard to the ion dependence of the blockade of reverse transport by uptake
      inhibitors.

PMID- 9154330
TI  - A neuromodulatory role for neuronal nitric oxide in the rabbit renal artery.
AB  - 1. The effects of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl
      ester (L-NAME) on vasoconstrictor responses to transmural electrical nerve
      stimulation and noradrenaline were examined in the rabbit isolated renal artery
      with and without an intact endothelium. In addition, the effect of removing the
      endothelium from the renal artery on vasoconstrictor responses to transmural
      electrical nerve stimulation and noradrenaline was also investigated.
      Immunohistofluorescence techniques were carried out to determine if there were
      any nitrergic nerves supplying the renal artery. 2. The vasoconstriction produced
      in response to transmural electrical nerve stimulation (2-64 Hz) was
      significantly enhanced in the presence of L-NAME (3 x 10(-6), 10(-5), 3 x 10(-5)
      and 10(-4) M). 3. L-NAME (3 x 10(-6), 10(-5), 3 x 10(-5) and 10(-4) M) did not
      significantly affect the maximum vasoconstriction produced in response to
      noradrenaline. However, the noradrenaline dose-response curve was significantly
      shifted to the left by the addition of L-NAME (3 x 10(-6), 10(-5), 3 x 10(-5) and
      10(-4) M). 4. The increase in the amplitude of the vasoconstriction, produced in
      response to transmural electrical nerve stimulation (16 Hz) and noradrenaline
      (10(-5) M) in the presence of L-NAME (10(-5) M) was not observed when L-arginine
      (10(-3) M) was added in addition to L-NAME (10(-5) M). 5. Removing the
      endothelium did not significantly affect the response to transmural electrical
      nerve stimulation (1-64 Hz). The maximum vasoconstriction in response to
      noradrenaline was also unaffected by the removal of the endothelium. The pD2
      value for noradrenaline obtained from vessels with no endothelium was
      significantly greater than the pD2 value obtained from vessels with an intact
      endothelium (5.90 +/- 0.11 and 5.16 +/- 0.03, respectively). 6. On renal artery
      segments with no endothelium L-NAME (3 x 10(-5) M) significantly enhanced the
      response to transmural electrical nerve stimulation (2-64 Hz). L-NAME did not
      affect the maximum response to noradrenaline. However, there was a significant
      shift to the right of the noradrenaline doseresponse curve in the presence of L
      NAME (3 x 10(-5) M). 7. Both nitric oxide synthase-containing and NADPH
      diaphorase stained nerves were located on the adventitial-medial border of the
      rabbit renal artery. 8. The present study has suggested a presynaptic inhibitory
      action for nitric oxide (probably derived from identified perivascular nitrergic
      nerves), on perivascular sympathetic vasoconstrictor nerve mediated responses of
      the rabbit renal artery. In contrast, the enhancement of the response to
      noradrenaline by L-NAME can be attributed to inhibition of the synthesis of
      endothelium-derived nitric oxide.

PMID- 9154331
TI  - In vitro differentiation of human monocytes to macrophages: change of PDE profile
      and its relationship to suppression of tumour necrosis factor-alpha release by
      PDE inhibitors.
AB  - 1. During in vitro culture in 10% human AB serum, human peripheral blood
      monocytes acquire a macrophage-like phenotype. The underlying differentiation was
      characterized by increased activities of the macrophage marker enzymes unspecific
      esterase (NaF-insensitive form) and acid phosphatase, as well as by a down
      regulation in surface CD14 expression. 2. In parallel, a dramatic change in the
      phosphodiesterase (PDE) profile became evident within a few days that strongly
      resembled that previously described for human alveolar macrophages. Whereas PDE1
      and PDE3 activities were augmented, PDE4 activity, which represented the major
      cyclic AMP-hydrolysing activity of peripheral blood monocytes, rapidly declined.
      3. Monocytes and monocyte-derived macrophages responded to lipopolysaccharide
      (LPS) with the release of tumour necrosis factor-alpha (TNF). In line with the
      change in CD14 expression, the EC50 value of LPS for induction of TNF release
      increased from approximately 0.1 ng ml-1 in peripheral blood monocytes to about 2
      ng ml-1 in macrophages. 4. Both populations of cells were equally susceptible
      towards inhibition of TNF release by cyclic AMP elevating agents such as
      dibutyryl cyclic AMP, prostaglandin E2 (PGE2) or forskolin, which all led to a
      complete abrogation of TNF production in a concentration-dependent manner and
      which were more efficient than the glucocorticoid dexamethasone. 5. In monocytes,
      PDE4 selective inhibitors (rolipram, RP73401) suppressed TNF formation by 80%,
      whereas motapizone, a PDE3 selective compound, exerted a comparatively weak
      effect (10-15% inhibition). Combined use of PDE3 plus PDE4 inhibitors resulted in
      an additive effect and fully abrogated LPS-induced TNF release as did the mixed
      PDE3/4 inhibitor tolafentrine. 6. In monocyte-derived macrophages, neither PDE3-
      nor PDE4-selective drugs markedly affected TNF generation when used alone (< 15%
      inhibition), whereas in combination, they led to a maximal inhibition of TNF
      formation by about 40-50%. However, in the presence of PGE2 (10 nM), motapizone
      and rolipram or RP73401 were equally effective and blocked TNF release by 40%.
      Tolafentrine or motapizone in the presence of either PDE4 inhibitor, completely
      abrogated TNF formation in the presence of PGE2. Thus, an additional cyclic AMP
      trigger is necessary for PDE inhibitors to become effective in macrophages. 7.
      Finally, the putative regulatory role for PDE1 in the regulation of TNF
      production in macrophages was investigated. Zaprinast, at a concentration showing
      80% inhibition of PDE1 activity (100 micromol l-1), did not influence TNF
      release. At higher concentrations (1 mmol l-1), zaprinast became effective, but
      this inhibition of TNF release can be attributed to a significant inhibitory
      action of this drug on PDE3 and PDE4 isoenzymes. 8. In summary, the in vitro
      differentiation of human peripheral blood monocytes to macrophages is
      characterized by a profound change in the PDE isoenzyme pattern. The change in
      the PDE4 to PDE3 ratio is functionally reflected by an altered susceptibility
      towards selective PDE inhibitors under appropriate stimulating conditions.

PMID- 9154332
TI  - Differential effects of omega-conotoxin GVIA on cholinergic and non-cholinergic
      secretomotor neurones in the guinea-pig small intestine.
AB  - 1. Ussing chambers were used to study the effects of the specific N-type Ca2+
      channel antagonist, omega-conotoxin GVIA, on neurally evoked secretion across
      isolated submucosa/mucosa preparations from the small intestine of the guinea
      pig. 2. Cholinergic and non-cholinergic neurones were stimulated with 10 microM
      dimethylphenylpiperazinium (DMPP). Non-cholinergic secretomotor neurones were
      preferentially stimulated with 100 nM 5-hydroxytryptamine (5-HT), while
      cholinergic secretomotor neurones were preferentially stimulated with 3 microM 5
      HT in the presence of the 5-HT2 receptor antagonist ketanserin (30 nM). 3. omega
      Conotoxin GVIA (1 nM-1 microM) depressed the secretion evoked by DMPP in a
      concentration-dependent manner, but a substantial residual response was observed.
      Hyoscine (100 nM) significantly depressed secretion evoked by DMPP, but did not
      prevent further depression of secretion by omega-conotoxin GVIA. 4. The toxin was
      substantially more effective when the non-cholinergic secretomotor neurones were
      preferentially activated with 100 nM 5-HT, with a decrease in the response of
      more than 75% of the control value in the presence of 1 microM omega-conotoxin
      GVIA. 5. omega-Conotoxin GVIA (1 microM) was relatively ineffective against
      secretion evoked by preferential activation of cholinergic secretomotor nuerones
      with 3 microM 5-HT in the presence of 30 nM ketanserin, inhibiting the response
      by less than 33%. However, this inhibition was significant. Both 100 nM hyoscine
      and 300 nM tetrodotoxin abolished this effect of omega-conotoxin GVIA. 6. It is
      concluded that N-type Ca2+ channels play a major role in transmitter release from
      non-cholinergic secretomotor neurones, but are not important for release from
      cholinergic secretomotor neurones in the guinea-pig small intestine.

PMID- 9154333
TI  - Differential modulation of AMPA receptor mediated currents by evans blue in
      postnatal rat hippocampal neurones.
AB  - 1. The modulation of non-N-methyl-D-aspartate (NMDA) receptor-mediated whole cell
      currents and of glutamatergic synaptic transmission by purified Evans Blue (EB)
      was investigated in rat cultured postnatal hippocampal neurones by use of patch
      clamp recordings and a fast drug application system. 2. Three different groups of
      neurones could be distinguished with respect to the type of modulation obtained
      with 10 microM EB: EB was either a predominant inhibitor of desensitization (13%
      of the neurones), a predominant inhibitor of current amplitudes (42%) or a mixed
      inhibitor of both properties (45%). Both effects were not use-dependent and
      reached maximal levels after 30 s of pre-equilibration with the diazo dye. 3.
      Dose-response curves obtained from glutamate activated whole cell currents
      yielded an IC50 value for EB of 13.3 microM (Hill coefficient: 1.3) for the
      inhibition of desensitization, and an IC50 value of 10.7 microM (Hill
      coefficient: 1.2) for the inhibition of current amplitudes. 4. Chicago acid SS
      (100 microM) which is one of the synthesis precursors of EB had no effect on
      current amplitudes of glutamate activated whole cell currents but was a weak
      inhibitor of desensitization in all hippocampal neurones investigated,
      irrespective of the type of modulation obtained with EB in the same neurone. 5.
      Oxidatively modified EB (the so-called VIMP (10 microM)) had no effect on the
      kinetics but was a partial inhibitor of glutamate-activated whole cell currents
      in all hippocampal neurones investigated. 6. EB (10 microM) inhibited the
      amplitudes of non-NMDA receptor mediated autaptic currents to the same extent (to
      39 +/- 19% of control) as observed for glutamate activated whole cell currents
      (to 41 +/- 17% and 56 +/- 20%). However, the decay of the autaptic responses
      remained uninfluenced upon EB application, indicating that either receptor
      desensitization does not dominate the time course of the synaptic response or
      that the non-NMDA receptors sensitive to modulation of desensitization by EB are
      not present in the postsynaptic membrane. 7. In conclusion, EB differentially
      modulates alpha-amino-3-hydroxy-5-methyl -4-isoxazole propionic acid (AMPA)
      receptor gating in different subsets of neurones. Upon identification of the
      cellular determinants for the differential modulation (e.g. AMPA receptor subunit
      composition) EB could become a useful tool to investigate receptor subtypes
      during electrophysiological recordings.

PMID- 9154334
TI  - Mechanism of enhanced vasoconstrictor hormone action in vascular smooth muscle
      cells by cyclosporin A.
AB  - 1. The use of the immunosuppressive drug cyclosporin A (CsA) is limited by two
      major side effects, nephrotoxicity and hypertension, which are caused by drug
      induced local vasoconstriction. We have recently shown that CsA potentiates the
      contraction of isolated resistance arteries to vasoconstrictor hormones and
      increases the calcium response to these agents in vascular smooth muscle cells
      (VSMC). The goal of the present study was to investigate further the molecular
      mechanism(s) involved in these effects. 2. Stimulation of VSMC with [Arg]8
      vasopressin (AVP) induced a concentration-dependent increase in total inositol
      phosphates (InsP) and cellular calcium response (as measured by 45Ca2+ efflux).
      Preincubation of VSMC with CsA increased both InsP formation and 45Ca2+ efflux.
      3. The potentiating effect of CsA on AVP-elicited InsP formation and 45Ca2+
      efflux was inhibited by co-incubation with the protein synthesis inhibitors
      actinomycin D and cycloheximide, indicating that CsA acted on gene expression. 4.
      Binding experiments with [3H]-AVP on VSMC showed that CsA increased the number of
      AVP receptors by about two fold without affecting receptor affinity. Actinomycin
      D completely blocked this increase. 5. These results demonstrate for the first
      time that incubation of VSMC with CsA increases the expression of AVP receptors,
      resulting in a potentiation of InsP formation and calcium response upon
      stimulation with AVP. This effect of CsA is likely to occur with other
      vasoconstrictor hormone receptors as well and could be a key mechanism in the
      induction of vasoconstriction, and subsequent drug-induced nephrotoxicity and
      hypertension.

PMID- 9154335
TI  - Comparison of the contractile effects and binding kinetics of endothelin-1 and
      sarafotoxin S6b in rat isolated renal artery.
AB  - 1. To date, only two mammalian endothelin (ET) receptors, termed ETA and ETB,
      have been cloned, sequenced and characterized. However, several functional
      studies of isolated blood vessels suggest that ET-1-induced contractions may be
      mediated by multiple ETA receptors. In this study, the ETA receptors in renal
      arteries isolated from Wistar rats were characterized by isometric tension
      recording and radioligand binding techniques. 2. ET-1, sarafotoxin S6b (StxS6b)
      and ET-3 produced concentration-dependent contraction with similar response
      maxima in endothelium-denuded arteries, whereas the ETB receptor-selective
      agonist StxS6c was inactive. ET-1 and StxS6b were equipotent and 30 times more
      potent than ET-3. This agonist profile, together with the findings that the ETA
      receptor-selective antagonists, BQ-123 and FR-139317 caused concentration
      dependent, rightward shifts of the concentration-effect curves to each agonist
      indicated that ET-1-induced contractions in rat renal artery were mediated via
      ETA receptors. 3. BQ-123 and FR-139317 were both significantly more potent
      inhibitors of contractions induced by StxS6b or ET-3 than of responses to ET-1,
      raising the possibility that a component of ET-1-induced contraction was mediated
      through atypical, BQ-123 (or FR-139317)-insensitive ETA receptors. However, in
      competition binding studies, specific [125I]-ET-1 and [125I]-StxS6b binding to
      rat renal artery sections was completely abolished by BQ-123 in a manner
      consistent with an action at a single site. Thus, competition binding studies did
      not provide any supportive evidence of the existence of a BQ-123-insensitive ETA
      receptor. 4. Additional studies revealed marked differences in the kinetics of
      [125I]-ET-1 and [125I]-StxS6b binding. Following a 3 h period of association of
      [125I]-ET-1 with its receptors, no significant dissociation of receptor-bound
      [125I]-ET-1 was observed during a 4 h washout period. In stark contrast,
      dissociation studies revealed that specific [125I]-StxS6b binding to ETA
      receptors was reversible (t0.5diss, 100 min). A series of association binding
      studies were also consistent with the specific binding of [125I]-ET-1 and [125I]
      StxS6b being irreversible and reversible processes, respectively. 5. Thus,
      differences in BQ-123 potency against ET-1 and StxS6b-induced contractions in rat
      renal arteries might be due to differences in the kinetics of agonist binding,
      rather than due to the existence of atypical ETA receptors.

PMID- 9154336
TI  - Suppressive effect of melatonin administration on ethanol-induced gastroduodenal
      injury in rats in vivo.
AB  - 1. Melatonin protection against ethanol-induced gastroduodenal injury was
      investigated in duodenumligated rats. 2. Melatonin, injected i.p. 30 min before
      administration of 1 ml of absolute ethanol, given by gavage, significantly
      decreased ethanol-induced macroscopic, histological and biochemical changes in
      the gastroduodenal mucosa. 3. Ethanol-induced lesions were detectable as
      haemorrhagic streaks. Ethanol administration damaged 36% and 25% of the total
      gastric and duodenal surface, respectively. Melatonin treatment reduced ethanol
      induced gastric and duodenal damage to 14% and 8%, respectively. When
      indomethacin was given together with ethanol, the gastric damaged area was 44% of
      the total surface, while the duodenal damaged area was 35%; melatonin
      administration reduced the damage to only 13% of the total gastric surface and to
      12% of total duodenal surface. 4. Both stomach and duodenum of ethanol-treated
      animals showed polymorphonuclear leukocyte (PMN) infiltration. The number of PMN
      increased more than 600 and 200 times in stomach and duodenum, respectively,
      following ethanol administration. Melatonin treatment reduced ethanol-induced PMN
      infiltration by 38% in the stomach and 20% in the duodenum. In indomethacin
      ethanol-treated rats, the number of PMN increased by 875% compared to control
      group in the stomach and by 264% in duodenum. Melatonin administration reduced
      the indomethacin-ethanol-induced PMN rise by 57% in the stomach and 40% in the
      duodenum. 5. Gastroduodenal total glutathione (tGSH) concentration and
      glutathione reductase (GSSG-Rd) activity were significantly reduced following
      ethanol and indomethacin-ethanol administration. Melatonin ameliorated both the
      decrease in tGSH concentration as well as the reduction of GSSG-Rd activity
      elicited by ethanol both in the stomach and duodenum; melatonin was effective
      against indomethacin-ethanol-induced damage only in the stomach. 6. Ethanol
      induced gastroduodenal damage is believed to be mediated by the generation of
      free radicals. Recently, a number of in vivo and in vitro experiments have shown
      melatonin to be an effective antioxidant and free radical scavenger; thus, we
      conclude that the protection by melatonin against ethanol-induced gastroduodenal
      injury is due, at least in part, to its radical scavenging activity.

PMID- 9154337
TI  - Synergistic interaction between endothelium-derived NO and prostacyclin in
      pulmonary artery: potential role for K+ATP channels.
AB  - 1. The aim of the present study was to assess interactions between nitric oxide
      (NO) and prostacyclin (PGI2) during endothelium-dependent relaxations evoked by
      bradykinin, calcium ionophore (A23187) and acetylcholine in canine isolated
      pulmonary artery. 2. Relaxations to low concentrations of bradykinin and A23187
      were abolished by combined inhibition of NO-synthase (by N omega-nitro-L-arginine
      methyl ester L-NAME, 30 microM) and cyclo-oxygenase (indomethacin, 10 microM),
      suggesting mediation by NO and PGI2. The individual contributions of NO and PGI2
      to the dilator responses were quantified by use of areas above the separate
      indomethacin-insensitive and L-NAME-insensitive components of the concentration
      effect curves, respectively. Individually, NO and PGI2 accounted for only 53 +/-
      5% and 16 +/- 9% of total bradykinin-induced relaxation, and 46 +/- 10% and 20 +/
      9% of total A23187-induced relaxation, suggesting that NO and PGI2 acted
      synergistically to cause endothelium-dependent relaxation. 3. Relaxation to low
      concentrations of acetylcholine was abolished by L-NAME but not affected by
      indomethacin, suggesting the response was mediated solely by NO with no
      interaction from PGI2. 4. Glibenclamide (1 microM), an inhibitor of ATP-sensitive
      potassium (K+ATP) channels, inhibited responses to bradykinin or A23187 but did
      not affect relaxations evoked by acetylcholine. Glibenclamide did not affect
      endothelium-independent relaxations to PGI2 or the NO-donor, 3
      morpholinosydnonimine (SIN-1). 5. With bradykinin, glibenclamide attenuated total
      relaxation by 49 +/- 8%, but did not alter the individual NO and PGI2-mediated
      components of the response. Glibenclamide abolished the synergistic interaction
      between endothelium-derived NO and PGI2. 6. At high concentrations, bradykinin,
      A23187 or acetylcholine caused endothelium-dependent relaxation that was
      insensitive to L-NAME + indomethacin. With bradykinin or A23187, this component
      of relaxation was inhibited by glibenclamide, whereas with acetylcholine,
      glibenclamide had no effect. 7. The synergistic interaction between endothelium
      derived NO and PGI2 in canine pulmonary artery is mediated by activation of K+ATP
      channels, presumably by an endothelium-derived hyperopolarizing factor (EDHF).
      The pattern of endothelial dilator mediators and the presence of this synergistic
      interaction is dependent on the nature of the endothelial stimulus.

PMID- 9154338
TI  - The in vitro pulmonary vascular effects of FK409 (nitric oxide donor): a study in
      normotensive and pulmonary hypertensive rats.
AB  - 1. Vasorelaxant responses to the nitric oxide (NO) donor, FK409 ((+/-)-(E)-4
      ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide ), were evaluated on
      precontracted isolated ring preparations of main pulmonary artery and intralobar
      pulmonary artery from rats. 2. On main pulmonary artery FK409 fully reversed the
      precontractions. Responses were inhibited by methylene blue but were independent
      of the endothelium. The potency (-log EC50) of FK409 was the same on preparations
      contracted with noradrenaline (7.62) or the thromboxane-mimetic, U44619 (7.63).
      3. On intralobar pulmonary artery FK409 caused only 80% reversal of the
      precontraction and was 2 fold less potent than on main pulmonary artery. These
      differences in maximum response and potency between main and intralobar arteries
      are in keeping with previous findings with other NO donors. 4. Pulmonary
      hypertension was induced in rats by chronic exposure to hypoxia (10% O2) for 1 or
      4 weeks. Main pulmonary arteries from 1 week hypoxic rats had inherent tone and
      showed spontaneous contractile activity. In these arteries FK409 reversed not
      only the precontraction induced by noradrenaline but also the inherent tone.
      However, FK409 was 17 fold less potent than in control arteries, reflecting
      previous findings with other NO donors. Main pulmonary arteries from 4 week
      hypoxic rats had minimal inherent tone and were quiescent and FK409 was 4.5 fold
      less potent than in control arteries. In intralobar pulmonary arteries from 4
      week hypoxic rats FK409 was 12 fold less potent than in controls. 5. Treatment of
      arteries with either (a) in vitro hypoxic conditions (PO2 of solution in organ
      bath < 10 mmHg) or (b) superoxide dismutase (SOD; 150 u ml-1) together with
      catalase (1200 u ml-1) significantly increased the potency of FK409 in
      preparations from hypoxic rats but had no effect on the potency in control
      preparations. Neither SOD nor catalase, alone, nor the nitric oxide synthase
      inhibitor, NG-nitro-L-arginine methyl ester, had any effect on the potency of
      FK409 in preparations from control or hypoxic rats. 6. It is concluded that the
      reduction in potency of FK409 seen in pulmonary arteries from rats with chronic
      hypoxic pulmonary hypertension may be due in part to the presence of one or more
      reactive oxygen species (either hydroxyl or superoxide plus hydrogen peroxide).

PMID- 9154339
TI  - Effects of phosphodiesterase inhibitors on human lung mast cell and basophil
      function.
AB  - 1. The non-hydrolysable cyclic AMP analogue, dibutyryl (Bu2)-cyclic AMP,
      inhibited the stimulated release of histamine from both basophils and human lung
      mast cells (HLMC) in a dose-dependent manner. The concentrations required to
      inhibit histamine release by 50% (IC50) were 0.8 and 0.7 mM in basophils and
      HLMC, respectively. The cyclic GMP analogue, Bu2-cyclic GMP, was ineffective as
      an inhibitor of histamine release in basophils and HLMC. 2. The non-selective
      phosphodiesterase (PDE) inhibitors, theophylline and isobutyl-methylxanthine
      (IBMX) inhibited the IgE-mediated release of histamine from both human basophils
      and HLMC in a dose-dependent fashion. IBMX and theophylline were more potent
      inhibitors in basophils than HLMC. IC50 values for the inhibition of histamine
      release were, 0.05 and 0.2 mM for IBMX and theophylline, respectively, in
      basophils and 0.25 and 1.2 mM for IBMX and theophylline in HLMC. 3. The PDE 4
      inhibitor, rolipram, attenuated the release of both histamine and the generation
      of sulphopeptidoleukotrienes (sLT) from activated basophils at sub-micromolar
      concentrations but was ineffective at inhibiting the release of histamine and the
      generation of both sLT and prostaglandin D2 (PGD2) in HLMC. Additional PDE 4
      inhibitors, denbufylline, Ro 20-1724, RP 73401 and nitraquazone, were all found
      to be effective inhibitors of mediator release in basophils but were ineffective
      in HLMC unless high concentrations (1 mM) were employed. 4. Neither 8
      methoxymethyl IBMX (PDE 1 inhibitor), zaprinast (PDE 5 inhibitor) nor a range of
      PDE 3 inhibitors (siguazodan, SKF 94120, SKF 95654) were effective inhibitors of
      mediator release from either basophils or HLMC. 5. In basophils, rolipram acted
      to potentiate the inhibitory effects of the adenylate cyclase activator,
      forskolin, whereas in HLMC, rolipram failed to potentiate the inhibitory effects
      of forskolin. 6. Extracts of purified HLMC and basophils hydrolysed cyclic AMP.
      IBMX (100 microM) inhibited the PDE activity in basophil extracts by 67 +/- 7% (P
      < 0.0001) and in HLMC extracts by 63 +/- 9% (P < 0.0005). The hydrolysis of
      cyclic AMP by basophil extracts was inhibited by the selective PDE inhibitors
      (all at 10 microM), rolipram (56 +/- 8%, P < 0.0001) and the mixed PDE 3/4
      inhibitor, Org 30029 (47 +/- 9%, P < 0.01), whereas 8-methoxymethyl IBMX,
      siguazodan and zaprinast were ineffective. In HLMC, rolipram, Org 30029, 8
      methoxymethyl IBMX, siguazodan and zaprinast all inhibited the hydrolysis of
      cyclic AMP by extracts to a significant (P < 0.05) and similar extent
      (approximately 25% inhibition at 10 microM). 7. In total, these data suggest that
      modulation of the PDE 4 isoform can regulate basophil responses whereas an
      association of the PDE 4 isoform with the regulation of HLMC function remains
      uncertain.

PMID- 9154340
TI  - Central involvement of kinin B1 and B2 receptors in the febrile response induced
      by endotoxin in rats.
AB  - 1. The effect of central injection of selective kinin B1 and B2 receptor
      antagonists on the febrile response induced by endotoxin (E. coli
      lipopolysaccharide, LPS) in rats was investigated. 2. Intracerebroventricular
      (i.c.v.) injection of a selective B2 receptor antagonist (Hoe-140, 8 nmol)
      reduced the early (0-2 h), but increased the late phase (4-6 h) of the febrile
      response induced by intravenous (i.v.) injection of LPS (0.5 microgram kg-1). 3.
      Co-administration of Hoe-140 (8 nmol, i.c.v.) with LPS (0.5 microgram kg-1,
      i.v.), followed 2.5 h later by the i.c.v. injection of a selective B1 receptor
      antagonist [des-Arg9-Leu8]-bradykinin (BK, 8 nmol), significantly reduced the
      febrile response induced by LPS throughout the whole experimental period. 4.
      Intravenous injection of Hoe-140 (1 mg kg-1) significantly reduced the febrile
      response induced by LPS (0.5 microgram kg-1, i.p.). 5. Pretreatment (24 h) with
      LPS (0.5 microgram kg-1, i.v.) reduced the febrile response induced by BK or
      [Tyr8]-BK (both, 5 nmol, i.c.v.), but markedly increased the febrile response
      induced by [des-Arg9]-BK (5 nmol, i.c.v.). The response induced by [des-Arg9]-BK
      in LPS-pretreated rats was significantly inhibited by co-injection of [des-Arg9
      Leu8]-BK (15 nmol, i.c.v.). 6. The results suggest that kinins are involved in
      the induction of LPS-induced fever and that central B2 and B1 receptors are
      activated during the initial and late phase of this response, respectively. The
      results also suggest that downregulation and/or desensitization of B2 receptors
      and induction and/or upregulation of B1 receptors in LPS-pretreated animals may
      have a significant pathophysiological role in the induction and maintenance of
      fever. These observations may be specifically important in the case of chronic
      inflammatory conditions, because the BK metabolite [des-Arg9]-BK, so far
      considered an inactive metabolite, acquires an active and relevant role with the
      progressive expression of B1 receptors that occurs in such states.

PMID- 9154341
TI  - Pharmacological evidence that the activation of the Na(+)-Ca2+ exchanger protects
      C6 glioma cells during chemical hypoxia.
AB  - 1. In C6 glioma cells exposed to chemical hypoxia a massive release of lactate
      dehydrogenase (LDH) occurred at 3 and 6 h, coupled with an increased number of
      propidium-iodide positive dead cells. 2. Extracellular Na+ removal, which
      activates the Na(+)-Ca2+ exchanger as a Na+ efflux pathway and prevents Na+
      entrance, significantly reduced LDH release and the number of propidium iodide
      positive C6 cells. 3. During chemical hypoxia, in the presence of extracellular
      Na+ ions, a progressive increase of [Ca2+]i occurred; in the absence of
      extracellular Na+ ions [Ca2+]i was enhanced to a greater extent. 4. The blockade
      of the Na(+)-Ca2+ exchanger by the amiloride derivative 5-(N-4-chlorobenzyl)
      2',4'-dimethylbenzamil (CB-DMB), lanthanum (La3+) and the Ca2+ chelator EGTA,
      completely reverted the protective effect exerted by the removal of Na+ ions on
      C6 glioma cells exposed to chemical hypoxia. 5. The inhibition of the Na(+)-Ca2+
      antiporter enhanced chemical hypoxia-induced LDH release when C6 glioma cells
      were incubated in the presence of physiological concentrations of extracellular
      Na+ ions (145 mM), suggesting that the blockade of the Na(+)-Ca2+ antiporter
      during chemical hypoxia can lead to increased cell damage. 6. Collectively, these
      results suggest that activation of the Na(+)-Ca2+ exchanger protects C6 glioma
      cells exposed to chemical hypoxia, whereas its pharmacological blockade can
      exacerbate cellular injury.

PMID- 9154342
TI  - A site-directed mutagenesis study on the conserved alanine residue in the distal
      third intracellular loops of cholecystokininB and neurotensin receptors.
AB  - 1. An alanine residue at the C-terminal tail of the third intracellular loop is
      highly conserved among various Gq protein-coupled receptors including rat
      cholecystokininB (CCKB) and neurotensin receptors. To investigate the functional
      significance of the conserved alanine in the activation of Gq proteins and
      phospholipase C (PLC) by CCKB and neurotensin receptors, the alanine residue was
      mutated in the present study. Subsequently, the ability of resulting mutant
      receptors to activate PLC was investigated by measuring the formation of inositol
      phosphates (IP) in COS-7 cells and recording Ca(2+)-activated chloride currents
      from Xenopus oocytes. 2. Site-directed mutagenesis was performed to mutate
      alanine at position 332 of rat CCKB receptor to glutamate. When the (A332E)
      mutant receptor was expressed in COS-7 cells and Xenopus oocytes, the efficacy
      and the potency of sulphated cholecystokinin octapeptide (CCK-8) to stimulate
      polyphosphoinositide hydrolysis in COS-7 cells and evoke calcium-dependent Cl-
      currents in oocytes were not significantly affected. 3. Alanine residue at
      position 302 of rat neurotensin receptor was also mutated to glutamate. When
      expressed in COS-7 cells and Xenopus oocytes, the resulting (A302E) mutant
      receptor was strongly defective in stimulating phosphatidylinositol turnover in
      COS-7 cells and evoking Ca(2+)-dependent chloride currents in oocytes. 4. In
      summary, the present study demonstrates that alanine residue at the C-terminus of
      third cytoplasmic domain is required for the full activation of Gq proteins and
      PLC by neurotensin receptors. However, in contrast to other Gq protein-coupled
      receptors, alanine at the distal third intracellular loop does not play a
      significant role in CCKB receptor activation of PLC.

PMID- 9154343
TI  - Constitutive activity of human prostaglandin E receptor EP3 isoforms.
AB  - 1. The human EP3 prostaglandin receptor is a seven transmembrane, G protein
      coupled receptor that couples to inhibition of adenylyl cyclase. The receptor
      occurs as at least six isoforms which result from alternative splicing. The
      isoforms are identical over the first 359 amino acids, comprising the seven
      transmembrane helices, but differ in the carboxyl terminal tail which ranges in
      length from 6 to 65 amino acids beyond the common region. 2. We have stably
      expressed in CHO-K1 cells four of the isoforms (EP3I-EP3IV) and a form of the EP3
      receptor (T-359) truncated at the carboxyl-terminal region defined by the
      alternative splicing site at amino acid number 359. 3. Isoforms EP3I and EP3II
      showed concentration-dependent inhibition of forskolin-stimulated adenylyl
      cyclase in CHO-K1 cells by the EP3 receptor agonist, sulprostone. The IC50
      calculated for sulprostone inhibition was 0.2 nM for EP3I and 0.15 nM for EP3II.
      The maximum extent of inhibition was 80% for both isoforms. 4. Isoforms EP3III
      and EP3IV showed marked constitutive activity, inhibiting forskolin-stimulated
      adenylyl cyclase in the absence of agonist. EP3IV also displayed some agonist
      dependent inhibition whereas EP3III was fully constitutively active. 5. The
      truncated receptor T-359 was fully constitutively active, inhibiting forskolin
      stimulated adenylyl cyclase by about 70% in the absence of agonist, and showed no
      agonist-dependent inhibition, in agreement with a similar truncation of the mouse
      EP3 receptor. 6. To confirm that differences in cyclic AMP level between isoforms
      represent constitutive activity, we treated cells with pertussis toxin for 6 h to
      abolish Gi function. Pertussis toxin reversed sulprostone-mediated inhibition of
      cyclic AMP formation in EP3I and EP3II and abolished constitutive activity of
      EP3III, EP3IV and T-359 so that the level of forskolin-stimulated cyclic AMP
      produced was the same in all cells and similar to that obtained in mock
      transfected cells. In mock-transfected cells, sulprostone had no effect on
      forskolin-stimulated cyclic AMP formation. 7. For these experiments we chose
      clones that showed similar expression levels of each isoform, as determined by
      binding of [3H]-prostaglandin E2 (PGE2) (EP3I, 0.71; EP3II, 1.47; EP3IV, 1.59
      pmol mg-1 protein). Mock-transfected cells showed no detectable binding of [3H]
      PGE2. In addition, we performed a detailed study of the effects of expression
      level on constitutive activity. Over a six fold range of expression there was no
      change in the properties of each isoform with regard to whether it was
      constitutively active or not. 8. The degree of constitutive activity correlated
      with the inverse of the length of the C-terminal tail of the isoforms. However,
      no correlation was found between isoforms from human and mouse: whereas EP3II
      shows no constitutive activity, its mouse homologue, EP3 gamma, shows almost
      complete constitutive activity, even though the C-terminal domains of the
      receptors following the splice site differ in only 7 of 29 amino acids.

PMID- 9154344
TI  - Actions of the anaesthetic Saffan on rat sympathetic preganglionic neurones in
      vitro.
AB  - 1. Whole-cell patch-clamp recordings were used to investigate the effects of the
      anaesthetic Saffan on the electrophysiological properties of sympathetic
      preganglionic neurones (SPNs) in rat spinal cord slices. 2. Saffan (1-54 microM)
      abolished or reduced the frequency of spontaneous action potential firing and
      abolished spontaneous, sub-threshold membrane potential oscillations. Saffan
      caused dose-dependent decreases in input resistance and depending upon the
      initial resting membrane potential, either a depolarization, a hyperpolarization
      or no change in membrane potential. 3. Responses to Saffan were blocked by the
      GABAA receptor antagonists bicuculline (5-20 microM) and picrotoxin (20 microM),
      but not by the glycine receptor antagonist strychnine (20 microM) indicating that
      they were mediated by GABAA receptors. 4. Changes in the properties of SPN action
      potentials were also observed. In the presence of Saffan the amplitude and
      duration of the action potential after-hyperpolarization were reduced and larger
      depolarizations were required in order to evoke trains of action potentials. 5.
      To examine the effects of Saffan on electrotonic coupling between SPNs,
      experiments were performed with the Na+ channel blocker QX-314 in the
      intracellular solution and antidromic oscillations were evoked by ventral root
      stimulation. Saffan failed to abolish antidromic oscillations, but reduced their
      amplitude and duration. This indicates that the abolition of spontaneous membrane
      potential oscillations was not a direct effect on the coupling between SPNs, but
      was a result of the abolition of spontaneous activity by Saffan. 6. The responses
      to Saffan occurred within the plasma concentration range of Saffan during
      anaesthesia, suggesting that the electrophysiological properties of SPNs may be
      altered during anaesthesia with Saffan. This would be expected to lead to changes
      in sympathetic tone and in the integration of sympathetic output.

PMID- 9154345
TI  - Effect of L-dopa alone and with benserazide on the spontaneous activity of
      striatal neurones in normal and 6-hydroxydopamine-lesioned rats.
AB  - 1. The effects of L-dopa methylester (LDME), an analogue of levodopa, on the
      spontaneous activity of dopamine sensitive neurones in the rat striatum, after 6
      hydroxydopamine induced degeneration of the nigrostriatal tract were compared
      with those in unlesioned animals both in the absence and presence of benserazide,
      a peripheral DOPA decarboxylase inhibitor (PDI). 2. Studies were performed at 5-7
      days post lesion (group 1 animals), at 21 days (group 2) when denervation
      supersensitivity was evident by contralateral turning to apomorphine and at the
      same time but following 7 days dosing with LDME plus benserazide (group 3). 3. In
      unlesioned animals, LDME alone inhibited spontaneous firing by some 45% over 60
      min including a marked but transient early phase which was still present in all
      lesioned animals even though the later inhibition was significantly reduced in
      group 1 and 3 animals. 4. When given after benserazide in unlesioned animals LDME
      still produced a similar level of overall inhibition but without the early phase.
      The lesion reduced the overall inhibition, except in group 2 animals, and after
      chronic dosing (group 3) it was almost absent. 5. It is proposed that since the
      early inhibition with LDME alone is still seen after lesion of the nigrostriatal
      tract but not after the PDI benserazide, it is caused by peripherally formed
      dopamine and that as the delayed inhibition with LDME alone and after benserazide
      are all reduced by nigrostriatal lesions, as is its amphetamine like ipsilateral
      turning, that this depends on locally (striatal) synthesized dopamine. 6. This
      study also shows the chronic levodopa/PDI treatment reduces the compensating
      increased activity of surviving dopaminergic neurones and the functional
      supersensitivity to dopamine and suggests that the long term administration of
      levodopa may reduce its own utilization and activity in the striatum and in the
      treatment of Parkinson's Disease [corrected].

PMID- 9154346
TI  - An examination of deoxyadenosine 5'(alpha-thio)triphosphate as a ligand to define
      P2Y receptors and its selectivity as a low potency partial agonist of the P2Y1
      receptor.
AB  - 1. The functional activity of deoxyadenosine 5'(alpha-thio)triphosphate (dATP
      alpha S) was assessed at the cloned human P2Y1 receptor stably expressed in
      1321N1 human astrocytoma cells and transiently expressed in Cos-7 cells. 2. Cells
      expressing the receptor responded to adenine nucleotides with an increase in [3H]
      inositol phosphate accumulation. Half-maximal responses were obtained at
      approximately 30 nM for 2-methylthioadenosine-5'-triphosphate (2MeSATP), 300 nM
      for dATP alpha S, and 1000 nM for adenosine 5'-triphosphate (ATP). dATP alpha S
      produced a maximal response that was only 37 +/- 4% of that produced by ATP or
      2MeSATP. dATP alpha S also competitively antagonized the phospholipase C response
      to 2MeSATP with a KB of 644 +/- 14 nM. Thus dATP alpha S acts as a low potency
      partial agonist at P2Y1 receptors. 3. The selectivity of dATP alpha S for P2Y1
      receptors was determined by examining its capacity to activate P2Y2, P2Y4 and
      P2Y6 receptors also stably expressed in 1321N1 cells. Although dATP alpha S was a
      partial agonist at P2Y1 receptors it was a full agonist at P2Y2 receptors, albeit
      with a potency that was two orders of magnitude lower than at P2Y1 receptors. No
      agonist or antagonist activity was observed at P2Y4 and P2Y6 receptors. 4.
      Although [35S]-dATP alpha S bound to a relatively high density (ca 10 pmol mg-1
      protein) of binding sites in membranes from 1321N1 or Cos-7 cells expressing the
      P2Y1 receptor, no difference in the total density of sites was observed between
      membranes from wild-type, empty vector-transfected, or P2Y1 receptor-expressing
      cells. Moreover, adenine nucleotide analogues inhibited [35S]-dATP alpha S
      binding with an order of potency that differed markedly from that for the
      accumulation of inositol phosphates in intact transfected P2Y1 receptor
      expressing cells. Saturation binding experiments demonstrated multiple affinity
      states for [35S]-dATP alpha S binding in wild-type Cos-7 cell membranes. These
      data from 1321N1 and Cos-7 cells suggest that cellular membranes exhibit a large
      number of high affinity binding sites for [35S]-dATP alpha S that are not related
      to P2Y receptor subtypes.

PMID- 9154347
TI  - Effect of copper on nitric oxide synthase and guanylyl cyclase activity in the
      rat isolated aorta.
AB  - 1. The potential role of copper (Cu2+) in modulating the activity of nitric oxide
      synthase (NOS) and guanylyl cyclase (GC) was investigated by use of
      diethyldithiocarbamic acid (DEDCA), a high affinity Cu2+ chelator. 2. DEDCA 100
      microM inhibited sodium nitroprusside (SNP; 0.005-10 microM)-evoked relaxation of
      rat isolated aortic rings precontracted with 3 microM phenylephrine (PE). A lower
      concentration of DEDCA (10 microM) did not significantly attenuate SNP-evoked
      responses but did inhibit relaxation to the endothelium-dependent dilator, A23187
      (0.01-10 microM). 3. The presence of 100 microM Cu2+, but not 100 microM Fe2+,
      alone enhanced A23187- and SNP-evoked relaxation of aortae precontracted with PE.
      4. The inhibitory effect of DEDCA on SNP- and A23187-induced relaxation was
      reversed by equimolar concentrations of Cu2+ but not Fe2+, indicating that DEDCA
      does not act via removal of haem-iron from the NOS and GC complexes. 5.
      Superoxide dismutase (30 mu ml-1) was without effect on the inhibition of DEDCA
      relaxation induced by either SNP or A23187 in aortae precontracted with PE. 6.
      When assessed by radioimmunoassay, DEDCA inhibited SNP- and A23187-stimulated
      cyclic GMP formation with IC50 values of 0.5 microM and 50 microM, respectively.
      7. These data demonstrate that Cu2+ plays a role in controlling NOS and GC
      activity in the rat aorta.

PMID- 9154348
TI  - Breast screening.

PMID- 9154349
TI  - Preparing to care for abused women. We depend on the four principles of family
      medicine.

PMID- 9154350
TI  - Space doctor. Similarities of medicine and astronautics.

PMID- 9154351
TI  - Tetanus boosters not cost-effective.

PMID- 9154352
TI  - Age-related macular degeneration: legal vs total blindness.

PMID- 9154353
TI  - College to continue leading role.

PMID- 9154355
TI  - Sugar group not part of CDA.

PMID- 9154354
TI  - Testing diagnostic acumen.

PMID- 9154356
TI  - Ominous practice pattern.

PMID- 9154357
TI  - Periconception folic acid supplementation. Knowledge and practice of Canadian
      family physicians.

PMID- 9154358
TI  - Ophthaproblem. Cytomegalovirus retinitis.

PMID- 9154359
TI  - Radiology rounds. Supracondylar fracture of the distal humerus.

PMID- 9154360
TI  - Recruiting women for breast screening. Family Physician Model strategy.
AB  - OBJECTIVE: To determine whether family physicians would participate in the Family
      Physician Model (FPM) recruitment strategy for mammography screening, whether
      participating physicians differed from non-participating physicians, and whether
      the strategy would recruit 70% of eligible women in the participating practices.
      DESIGN: Family physicians were invited to participate in the project. Staff from
      the Ontario Breast Screening Program-Hamilton Centre (OBSP-H) identified eligible
      women, prepared personalized letters recommending screening, and monitored
      compliance. Participating and non-participating physicians were asked to complete
      a questionnaire. SETTING: Family practices in Dundas, Ancaster, and Hamilton,
      Ont. PARTICIPANTS: Women aged 50 years and older who met eligibility criteria for
      screening. Family physicians in Dundas, Ancaster, and Hamilton. INTERVENTION:
      Family physicians were approached by the Health Promotion Officer at the OBSP-H
      about participating in the FPM. Eligible women in their practices were sent
      letters recommending breast screening. MAIN OUTCOME MEASURES: Percentage of
      family physicians agreeing to participate in the FPM, characteristics of
      participating and non-participating physicians, and percentage of eligible women
      who scheduled mammograms. RESULTS: Of the 114 family physicians approached, 76
      (67%) agreed to participate. Significantly more participating than non
      participating physicians were in group practice and had certification in family
      medicine. In response to the letters, 54% of eligible women obtained mammograms.
      Because 12% of women were ineligible since they had been referred for screening
      within the previous 12 months, 66% of women in the participating practices
      actually obtained mammograms over the 2-year period-almost the target 70%.
      CONCLUSION: The FPM is a successful recruitment strategy.

PMID- 9154362
TI  - Long-term attendance at a family practice teaching unit. Qualitative study of
      patients' views.
AB  - OBJECTIVE: To identify the factors that contribute to patients' long-term
      attendance at a family practice teaching unit. DESIGN: Qualitative method of
      focus groups. SETTING: A community-based family practice teaching unit in
      southwestern Ontario. PARTICIPANTS: Patients who had been coming to St Joseph's
      Family Medical Centre for more than 15 years were purposefully selected to
      participate. METHOD: Five focus groups composed of patients who had been
      affiliated with one of the three practices at the Centre for more than 15 years
      explored factors contributing to long-term attendance. MAIN FINDINGS: Four key
      themes were identified as the primary factors contributing to long-term
      attendance: the relationship context, the team concept, professional
      responsibility and attitudes, and comprehensive and convenient care. CONCLUSION:
      The resource-rich era of medical care, during which participants formulated their
      views and opinions about the factors contributing to their long-term attendance
      at a family practice teaching unit, has come to a close. The findings of this
      study provide important information that could help maintain one of the basic
      tenets of family medicine-continuity of care.

PMID- 9154361
TI  - Medication use and rural seniors. Who really knows what they are taking?
AB  - OBJECTIVE: To determine whether listings of current medications obtained from the
      office file of patients' attending physicians and the pharmacy record of
      patients' dispensing pharmacists corresponded to the actual use of medications in
      a group of non-institutionalized seniors residing in rural communities. DESIGN:
      In-home interviews followed by retrospective office chart and pharmacy database
      reviews. SETTING: Two rural communities in southern Alberta with populations of
      less than 7000 people. PARTICIPANTS: Twenty-five patients aged 75 years or older
      residing in the study communities, eight family physicians, and four dispensing
      pharmacies. MAIN OUTCOME MEASURES: Number of currently consumed prescription
      drugs, currently consumed over-the-counter (OTC) drugs, and stored or
      discontinued prescribed medications; knowledge of medications (prescribed, OTC,
      and stored) by family physicians and pharmacists; and number of prescribers or
      dispensing pharmacists. RESULTS: Patients took a mean of 56 prescribed
      medications, took a mean of 3.5 OTC medications, and had a mean of 2.0 stored or
      discontinued medications. Attending family physicians and primary dispensing
      pharmacists typically knew of only some of their patients' entire regimen of
      medications. CONCLUSIONS: Misinformation about medication consumption by seniors
      was common among health care providers. Undertaking routine medication reviews
      (with emphasis on OTC use), asking specific questions about actual consumption,
      encouraging use of one prescriber and one pharmacist, discouraging storage of
      discontinued medications and reducing use of medication samples should be of
      benefit.

PMID- 9154363
TI  - Vitamin B12 replacement. To B12 or not to B12?
AB  - OBJECTIVE: To review the evidence for an expanded approach to identifying and
      treating patients with cobalamin deficiency. Controversy surrounds this issue.
      Some authors claim that seven times more patients are treated than have true
      deficiency. New diagnostic tests and identification of patients who have
      neurologic consequences without hematologic abnormalities suggest that some of
      these patients have a vitamin B12 tissue deficiency. QUALITY OF EVIDENCE: A
      MEDLINE search of English-language literature from 1990 to 1995 revealed
      retrospective and prospective studies of diagnostic tests; prospective surveys; a
      cohort study; and retrospective and prospective case series, some with control
      groups. No double-blind controlled trials of treatment were found. MAIN FINDINGS:
      Some patients with neuropsychiatric abnormalities develop a cobalamin tissue
      deficiency that can be detected by elevated serum homocysteine and methylmalonic
      acid levels despite normal serum vitamin B12 levels without macrocytic anemia.
      Serum cobalamin testing is neither sensitive nor specific in the low normal range
      for cobalamin deficiency. Treatment recommendations vary because no controlled
      trials support any recommendations. Oral cobalamin is an underused alternative to
      parenteral treatment. CONCLUSION: Until the newer diagnostic tests become widely
      available, family physicians must continue to take a traditional approach to
      diagnosing vitamin B12 deficiency. There is, however, support for a clinical
      trial of treatment in patients with neuropsychiatric symptoms.

PMID- 9154364
TI  - Referral to specialized geriatric services. Which elderly people living in the
      community are likely to benefit?
AB  - PROBLEM BEING ADDRESSED: As the Canadian population ages, family physicians
      encounter increasing numbers of elderly people with medical, functional,
      psychological, and social difficulties. In the past two decades, most regions of
      Canada have developed systems of specialized geriatric services, available on a
      consultative basis, to assist family physicians evaluating and managing elderly
      patients with these difficulties. For many family physicians, however, it is
      often unclear which of their elderly patients are likely to benefit from referral
      to these geriatric services. OBJECTIVE OF PROGRAM: Using an interdisciplinary
      approach, specialized geriatric services seek to optimize health, maximize
      function, promote independence, and prevent or delay institutionalization of
      elderly people. Yet not all elderly people benefit from referral to specialized
      geriatric services. This article offers a clear and clinically practical
      framework to help family physicians identify elderly patients in their practices
      who are likely to benefit from referral to specialized geriatric services. MAIN
      COMPONENTS OF PROGRAM: By synthesizing previous work on the concept of frail
      elderly persons into a 2 x 2 matrix, the level and intensity of geriatric
      intervention most appropriate for different segments of the elderly population is
      clarified. CONCLUSIONS: Using the simple approach described in this article,
      family physicians should be able to use available geriatric resources easily and
      efficiently to optimize the health and function of their elderly patients.

PMID- 9154365
TI  - Mantoux (tuberculosis) testing. Evaluation of guidelines for testing in Canadian
      institutions.
AB  - OBJECTIVE: To evaluate the guidelines for Mantoux testing and isoniazid (INH)
      prophylaxis in various institutions and shelters for the homeless in Canada in
      light of research in Canada and other industrialized countries. DATA SOURCES:
      MEDLINE searches from January 1980 to June 1996 yielded 219 articles, some of
      which were case reports. The bibliographies of these articles were searched for
      relevant titles. A further search adding the words randomized, controlled trial
      and controlled clinical trial yielded two citations, neither of which was a
      randomized, controlled trial. DATA EXTRACTION: Studies were included if they
      described the incidence, screening, diagnosis, or prophylaxis of tuberculosis
      (TB), in institutions in Canada. DATA SYNTHESIS: Studies of staff patients in
      institutions tend to be incomplete in reporting exposure to TB, extent of Mantoux
      testing, and whether INH prophylaxis was completed. CONCLUSIONS: Institutions
      admitting patients with TB should follow the 1996 recommendations of the Canadian
      Thoracic Society (CTS). The best way to implement the recommendations is to have
      a TB control officer who administers protocols to identify staff and patients at
      risk for TB and a committee that regularly monitors implementation of CTS
      guidelines.

PMID- 9154366
TI  - What information do physicians receive from pharmaceutical representatives?
AB  - OBJECTIVE: To assess the information pharmaceutical sales representatives provide
      to physicians. DATA SOURCES: A MEDLINE search from January 1966 to May 1996 was
      done using combinations of the terms pharmaceutical industry, drug information
      services, drug utilization, physician's practice patterns and prescriptions, and
      drugs. Studies identified from this search were supplemented by material from my
      personal library. STUDY SELECTION: Studies had to be conducted in industrialized
      countries, based on direct observations of actual physician and sales
      representative contacts, and reporting quantitative results on the quality of
      information transmitted. SYNTHESIS: Four studies were included. Representatives
      usually mentioned the indications for their drugs, but omitted safety
      information. Representatives' information frequently contained inaccuracies.
      CONCLUSION: Sales representatives present only selected, usually positive,
      information about their products. Canadian doctors should not be passive
      recipients of information provided by sales representatives. Physicians who
      choose to continue to see representatives must critically compare the information
      they get from them with that contained in scientific publications.

PMID- 9154367
TI  - New Ontario familial breast cancer registry to facilitate genetic and
      epidemiologic studies.

PMID- 9154368
TI  - Adult attention-deficit hyperactivity disorder: assessment guidelines based on
      clinical presentation to a specialty clinic.
AB  - Of 143 adults presenting for attention-deficit hyperactivity disorder (ADHD)
      evaluation, 46 (32%) clearly met diagnostic criteria, 46 (32%) clearly did not
      meet diagnostic criteria, and another 51 (36%) with current ADHD-like features
      did not meet criteria due to either a lack of childhood history and/or
      complicating severe psychiatric or substance abuse comorbidity. The three groups
      were similar in demographics, psychiatric diagnosis, psychiatric symptom
      severity, and functional impairment. Compared with the group not meeting ADHD
      criteria, patients with ADHD had more frequent histories of learning disability
      in childhood, poorer reading scores on the Wide-Range Achievement Test (WRAT),
      poorer scores on the Continuous Performance Test (CPT), and higher scores on the
      Wender-Utah Rating Scale (WURS) for ADHD. Patients in the ambiguous ADHD category
      had higher rates of current substance abuse than the other two groups. While this
      group resembled the non-ADHD group in having a low incidence of learning
      disability and normal reading scores, their poor performance on the CPT and high
      scores on the WURS more closely resembled those of ADHD patients. These findings
      suggest that there are a few rating scales, testing instruments, and lifetime
      history characteristics that help to clarify the difficult diagnostic distinction
      between adult patients who do and do not have ADHD.

PMID- 9154369
TI  - Diagnostic comorbidity in hospitalized adolescents with conduct disorder.
AB  - We compared the diagnostic comorbidity of DSM-III-R axis I and axis II disorders
      in a sample of hospitalized adolescents with conduct disorder (CD) and a
      comparison group of hospitalized adolescents without conduct disorder (non-CD).
      Of 138 consecutively evaluated adolescents, 76 patients met criteria for CD and
      62 did not. On axis I, CD was significantly comorbid with attention-deficit
      hyperactivity disorder (ADHD) and substance use disorders (SUDs). None of the
      personality disorders assessed showed differential association with CD. The
      comorbid relationships found within this sample suggest a strong association
      between CD, ADHD, and SUD in hospitalized teenagers. This finding underscores the
      clinical importance of conducting a thorough developmental assessment and, when
      indicated, of treating ADHD and SUD in conduct-disordered adolescents.

PMID- 9154370
TI  - Prevalence of axis I disorders in an AIDS cohort: a cross-sectional, controlled
      study.
AB  - The primary purpose of this study was to assess the prevalence of major
      psychiatric disorders in human immunodeficiency virus-positive (HIV+) men with
      acquired immune deficiency syndrome (AIDS)-defining conditions. Secondary goals
      were to identify correlates of distress and psychopathology, and to determine
      whether there is a gradient of distress associated with progressive HIV illness.
      One hundred twelve men with AIDS-defining conditions, 61 HIV+ men without AIDS,
      and 84 HIV-seronegative gay men were assessed. Measures included the Structured
      Clinical Interview for DSM-IV (SCID), Hamilton Rating Scale for Depression (HAM
      D), and other dimensional measures of distress and outlook, as well as laboratory
      markers of HIV stage, including HIV RNA viral load assays. Rates of major
      depression, consistent with other findings, were in the 5% to 10% range. Mean
      scores on dimensional measures of distress and outlook were within the "not
      depressed" range and did not increase despite increasing HIV illness severity.
      However, rates of dysthymia were elevated among men with CD4 cell counts less
      than 500, and the cumulative rates of any current axis I depressive disorder for
      three of the four study groups were in the range of 15% to 20%. The strongest
      correlates of dimensional measures of distress were current HIV symptoms and
      social support, and to a lesser extent, a lifetime history of major depression
      and current use of antidepressants and/or anxiolytics. Overall, most men
      displayed effective adaptation to illness, but a significant minority experienced
      moderate psychological distress, which warrants consideration by health providers
      who serve this population.

PMID- 9154371
TI  - Psychiatric comorbidity differences in male and female adult psychiatric
      inpatients with substance use disorders.
AB  - To examine gender differences in the co-occurrence of DSM-III-R axis I disorders
      and axis II personality disorders in young adult psychiatric inpatients with
      substance use disorders (SUDs), a consecutive series of 70 inpatients (33 men and
      37 women) with SUD were reliably assessed with structured diagnostic interviews.
      Higher rates of dysthymia and eating disorders were observed in SUD females and
      higher rates of cluster A personality disorders were observed in SUD males. No
      gender differences were found for depression or anxiety in our SUD inpatients;
      these findings contrast with gender ratios for these disorders in the general
      population. In conclusion, relatively few gender differences were found in young
      adult inpatients with SUD, even where they would be expected based on general
      population gender patterns.

PMID- 9154372
TI  - Alexithymia in chronic pain patients.
AB  - Prior studies of alexithymia in chronic pain patients have used unvalidated
      alexithymia measures or have not controlled for treatment-seeking status. In this
      study, we compared 30 patients with chronic pain and patients seeking treatment
      for two other problems: nicotine dependence (n = 32) or moderate obesity (n =
      25). Alexithymia was assessed with the well-validated Toronto Alexithymia Scale
      (TAS) and also with the Alexithymia Provoked Response Questionnaire (APRQ). On
      both alexithymia measures, chronic pain patients were more alexithymic than
      nicotine-dependent and obese patients; the latter two groups did not differ.
      Chronic pain patients had greater psychopathology on the Minnesota Multiphasic
      Personality Inventory-2 (MMPI-2), and both alexithymia measures correlated
      positively with certain types of psychopathology. We conclude that alexithymia is
      increased among patients with chronic pain, that this relationship is not
      confounded by a treatment-seeking bias, and that alexithymia may contribute to
      both chronic pain and psychopathology.

PMID- 9154373
TI  - Secondary alexithymia as a state reaction in panic disorder and social phobia.
AB  - In a 6-month follow-up study, a change in alexithymia was examined in two samples
      of 26 patients with panic disorder and 24 patients with social phobia. Before
      psychiatric treatment, the prevalence rate of alexithymia, measured by the 20
      Item Toronto Alexithymia Scale (TAS-20), was higher for both panic disorder (54%)
      and social phobia (58%) groups than for healthy persons (15%). After treatment,
      scores on the alexithymia constructs of difficulty identifying feelings and
      difficulty describing feelings significantly decreased in panic disorder and
      social phobia patients. The overall decrease in measures of alexithymia in both
      groups was significantly related to reduction in anxiety, but not depression. The
      results suggest that secondary alexithymia related to anxiety exists as a state
      reaction in patients with panic disorder and social phobia.

PMID- 9154374
TI  - Nonpsychotic thought disorder: objective clinical identification of somatization
      and antisocial personality in language patterns.
AB  - This report describes a new method of using language patterns to identify
      somatization and antisocial personality (ASPD) disorders in clinical practice. A
      set of definitions describing characteristic speech patterns was developed to
      identify "nonpsychotic thought disorder" (NPTD). Speech patterns of subjects with
      somatization disorder and/or ASPD were compared with those of controls. Blind
      raters assessed audiotaped samples of speech obtained through open-ended
      interviews for instances of elements of NPTD. Women with somatization or ASPD had
      significantly more NPTD speech responses than controls, and women with both
      disorders showed the greatest amount. Antisocial men did not demonstrate more
      NPTD than controls, nor was somatization in men associated with NPTD. Clinical
      attention to speech patterns in patients may help alert clinicians to these
      disorders in women and serve as indicators for screening for these disorders.
      More study is needed to develop psychometric properties of the instruments on
      larger samples, and to identify speech indicators of personality disorder in men.
      It is likely that other personality disorders, e.g., borderline personality
      disorder, can be identified through speech patterns, and they deserve study with
      these methods.

PMID- 9154375
TI  - Mental disorder in adults with mental retardation and epilepsy.
AB  - The controversy regarding the exact nature of the relationship between
      psychopathology and epilepsy continues. We studied the rate of mental disorder in
      150 adults with mental retardation and epilepsy among the residents of a health
      district of the United Kingdom who lived either in institutions or in the
      community, and compared them with an age-, sex-, and IQ-matched nonepileptic
      adult mentally retarded population from the same institution and community.
      Mental disorder was assessed under three headings, namely severe maladaptive
      behavior, psychiatric illness according to ICD-9 criteria, and personality
      disorder. Sixty-five percent of the whole cohort had a diagnosis of mental
      disorder, and 55% showed severe maladaptive behavior. No significant difference
      in the rate of mental disorder emerged between the epileptic and nonepileptic
      groups, although the institutionalized subjects as opposed to the community-based
      subjects and severely mentally retarded adults compared with the mild to
      moderately mentally retarded adults showed a significantly higher rate of mental
      disorder in general and severe maladaptive behavior in particular. We
      hypothesized that underlying brain damage rather than epilepsy per se is a
      stronger determinant of psychopathology in the studied patient group.

PMID- 9154376
TI  - A comparative analysis of Minnesota Multiphasic Personality Inventory profiles of
      anorexia nervosa at hospital admission, discharge, and 10-year follow-up.
AB  - The assessment of personality variables measured by the Minnesota Multiphasic
      Personality Inventory (MMPI), was compared in a sample of 52 female inpatients
      with anorexia nervosa at the time of hospitalization, discharge from hospital,
      and 10 years after treatment. Admission MMPI scores were significantly higher
      than scores both at discharge and 10 years later. There were no significant
      overall differences between discharge and follow-up evaluation. Discharge, but
      not admission, MMPI scores were positively correlated with 10-year follow-up
      study on seven of 10 clinical MMPI scales (all but hypochondriasis,
      masculinity/femininity, and hypomania). At follow-up evaluation, eating disorder
      poor outcome was associated with higher MMPI scores. There was no significant
      difference on admission MMPI scores between the four outcome groups; however,
      patients who recovered had a greater decrease in MMPI scores at the 10-year
      follow-up study compared with poor outcome patients. The long-term outcome of
      anorexia nervosa was largely unrelated to the severity of psychopathology during
      the acute phase of the illness. These results suggest that persistent personality
      features are best measured following treatment of acute symptomatology of
      anorexia nervosa.

PMID- 9154377
TI  - A histochemical study of the distribution of dextran 500 in human corneas during
      organ culture.
AB  - PURPOSE: The aim of this histochemical study was to demonstrate the absorption of
      dextran 500 and its distribution in the cornea after storage under standard eye
      bank conditions. Furthermore, an attempt was made to distinguish between the
      soluble and insoluble parts of dextran 500 absorbed by the cornea, in order to
      see how much dextran remains in the cornea after transplantation. METHODS: Forty
      nine fresh and 65 organ-cultured human corneas were investigated. The corneas
      were cultured for 28 days in a dextran-free medium, followed by a period of 1-14
      days in a medium containing 5% dextran 500. Cryosections were stained by aqueous
      PAS and a modified alcoholic PAS to determine the amount of dextran. RESULTS:
      Dextran was not found in the epithelium, stroma or endothelium of fresh human
      corneas. By contrast, extra- and intracellular positive staining reactions were
      detected in corneas following storage in a medium containing dextran. Dextran 500
      absorption was relatively diffuse in the epithelium after storage in a dextran
      medium. Initial accumulations were found in the stroma near Bowman's and
      Descemet's membranes and also in the central part of the cornea, as the period of
      culture in the medium containing dextran lengthened. We also observed interaction
      between the stroma and endothelium: decreasing amounts in the endothelium were
      followed by an increase of same in the stroma. Intracellular deposits of dextran
      were detected after only one day. A much greater part of the extracellular
      dextran than previously described was found to be insoluble. CONCLUSIONS: As the
      amount of dextran in the cornea increases over a longer storage time, we conclude
      that the period of storage in a medium containing dextran should be limited to
      four days. The fact that the cornea is saturated with dextran after seven days
      has been shown in further studies to interfere with mitochondrial function and
      may also cause severe post-operative swelling of the transplant, hence leading to
      a longer recovery period for the patient.

PMID- 9154378
TI  - Proteoglycan expression by human trabecular meshworks.
AB  - PURPOSE: Proteoglycans may serve important roles in trabecular meshwork structure
      or function. Detailed molecular characterization and identification of specific
      trabecular proteoglycan core proteins has been limited. METHODS: Radiolabeled
      proteoglycans were extracted from cultured human trabecular meshworks and
      subjected to ion exchange and molecular sieve chromatography. Peaks were
      subjected to glycosaminoglycan content analysis. Reverse transcription with
      polymerase chain reaction was used to identify trabecular mRNAs of several common
      proteoglycan core proteins. Western immunoblots of trabecular extracts were also
      utilized to identify these proteoglycan core proteins. RESULTS: The proteoglycans
      elute from ion exchange columns at high salt and molecular sieve column profiles,
      and they exhibit broad peaks typical of the proteoglycan microheterogeneity seen
      in other tissues. The four common glycosaminoglycan side-chains were identified
      on these proteoglycans. Trabecular cells in organ or cell culture contain mRNAs
      coding for decorin, biglycan, versican, perlecan and a basement membrane
      glycoprotein, SPARC. Syndecan-1 transcripts were present at very low levels,
      while aggrecan transcripts were not detectable. Decorin, biglycan, versican and
      perlecan core proteins were also identified by immunoblots of trabecular cell
      extracts. CONCLUSIONS: Several common proteoglycans are expressed by trabecular
      cells in organ explant or cell culture. Their general characteristics are not
      unlike those found in other tissues. These proteoglycans may serve important
      functions in the trabecular outflow pathway.

PMID- 9154379
TI  - The role of retinotomy in an experimental rabbit model of proliferative
      vitreoretinopathy.
AB  - PURPOSE: To create a model of proliferative vitreoretinopathy (PVR) using
      retinotomy with vitrectomy, cryotherapy, and platelet-rich plasma (PRP)
      injection, which more closely resembles the human pathophysiologic condition.
      METHODS: One hundred and twenty albino rabbits were divided into 10 groups of 12
      rabbits each and underwent the following procedures: group 1, vitrectomy; group
      2, cryotherapy; group 3, PRP intravitreous injection; group 4, retinotomy; group
      5, retinotomy and vitrectomy; group 6, retinotomy and cryotherapy; group 7,
      retinotomy and PRP injection; group 8, retinotomy, vitrectomy, and cryotherapy;
      group 9, vitrectomy, cryotherapy, and PRP injection and group 10, retinotomy,
      vitrectomy, cryotherapy, and PRP injection. All animals underwent follow-up
      examinations with indirect ophthalmoscopy and fundus photography on days 1, 3, 7,
      10, 14, 21, and 28 after the procedure(s). Retinal changes were categorized
      according to the classification of Fastenberg et al. At the end of the
      experiments, the eyes were enucleated, and examined under light and electron
      microscopy. RESULTS: No retinal detachments (RDs) were observed in groups 1, 2,
      4, 5, 6, and 8. RDs of varying severity were observed in group 3 (n = 1), group 7
      (n = 2), group 9 (n = 6), and group 10 (n = 12). Light and transmission electron
      microscopy confirmed the findings. CONCLUSIONS: Combining retinotomy with
      vitreous removal, cryotherapy, and PRP injection creates an efficient and
      different model of PVR that produced RD in 100% of rabbit eyes.

PMID- 9154380
TI  - PGE2 synthesis and response pathways in cultured corneal endothelial cells: the
      effects of in vitro aging.
AB  - PURPOSE: The purpose of these studies is to develop an in vitro model of corneal
      endothelial aging and to investigate age-related changes in morphology, mitosis,
      prostaglandin synthesis and prostaglandin response pathways. METHODS: First
      passage rabbit corneal endothelial cells were grown in vitro for up to 30 days
      after subculture. PGE2 synthesis was measured by radioimmunoassay. EP2 receptors
      were evaluated, by determination of PGE2 stimulated by flow cytometry and by
      bromodeoxyuridine (BrdU) incorporation in subconfluent, confluent and injured
      cultures. RESULTS: Rabbit corneal endothelial cells become less dense and more
      irregular in shape as they age in culture, thus resembling their in vivo
      counterparts. PGE2 synthesis and response decrease with culture age. Injury
      results in enhanced PGE2 synthesis in both younger and older cultures. In younger
      cultures, injury also results in mitosis of cells at the wound margin, and this
      response is greatly diminished in older cultures. CONCLUSIONS: The morphologic
      and mitotic changes seen in rabbit corneal endothelial cultures in vitro resemble
      those seen as a consequence of aging in humans and rabbits. Prostaglandin
      synthesis and response pathways are modified as a result of aging and may play a
      role in the autocrine regulation of wound repair, especially in younger cells.

PMID- 9154381
TI  - Cytoplasmic Ca2+ mobilization and Ca(2+)-dependent membrane currents in dispersed
      bovine ciliary muscle cells.
AB  - PURPOSE: The dependence of plasmalemma Ca2+ influx and Ca2+ release from
      intracellular stores on Ca2+ activated K+ channels of bovine ciliary muscle (CM)
      cells were examined. METHODS: The nystatin-perforated patch clamp technique for
      the measurement of membrane currents and a microscope based fura-2 fluorescence
      imaging of [Ca2+]i were applied to CM cells freshly dissociated with collagenase
      and identified with smooth muscle-specific alpha-isoactin. RESULTS: At holding
      voltages (VH) of > -60 mV, CM cells showed spontaneous transient outward currents
      (STOCs) and caffeine (> 10(-4) M) induced large transient outward currents
      (ICAF). Both STOCs and ICAF were abolished by tetraethylammonium chloride (10(-3)
      M) and charybdotoxin (10(-7) M), but not by apamin (10(-6) M), suggesting that
      both currents are mediated by Ca(2+)-activated K+ channels similar to those with
      medium (MK) or large (BK-type) conductance. Both STOCs and ICAF were gradually
      abolished in the nominally Ca(2+)-free and Co(2+)-containing solutions but were
      resistant to L-type Ca2+ channel blockers, including nicardipine, verapamil and
      diltiazem and a N-type channel blocker, omega-contoxin. The [Ca2+]i-elevation
      during high K+ (100 mM)-depolarization was prevented by Ca(2+)-free and Co(2+)
      containing solutions but not by nicardipine. CONCLUSIONS: These results suggest
      that CM cells possess MK or BK type-like Ca(2+)-activated K+ channels and that L
      type Ca2+ channels play minor roles for the maintenance of Ca(2+)-dependent
      responses in contrast to other types of smooth muscle cells.

PMID- 9154382
TI  - Dye spread through gap junctions in the corneal epithelium of the rabbit.
AB  - PURPOSE: Microelectrode dye injection of 5,6-carboxyfluorescein was used to
      investigate gap junctional communication in the corneal epithelium. METHODS: Dye
      injection started in the superficial layer and proceeded stepwise into the
      underlying epithelial layers until spread was observed. Intracellular [Ca2+] was
      manipulated by exposing the cornea to the calcium ionophore A23187 (global
      increase) or by increasing the [Ca2+] in the injection electrode (source cell
      increase). Intracellular pH was manipulated by exposing the cornea to nigericin
      in a low-pH KCI Ringer's (global decrease) or by lowering the pH in the injection
      electrode (source cell decrease). Heptanol was tested for its ability to uncouple
      gap junctions. Gap junctional communication was based on the layer at which
      spread was first observed and on the apparent dye travel distance from the point
      of injection. RESULTS: Control dye spread occurred, on average, in the third
      layer from the surface. Increased [Ca2+] in the source cell resulted in an
      initial spread occurring in the second layer. Globally increasing [Ca2+] with
      A23187 resulted in no change in the average initial spread layer. Lowering
      intracellular pH of the source cell did not affect the initial dye spread layer.
      Globally lowering intracellular pH resulted in significant gap junctional
      inhibition in a time-dependent manner. Dye spread distance was not significantly
      affected by [Ca2+] or pH manipulations. Heptanol (2.5 mM) completely inhibited
      dye coupling. CONCLUSION: All cell layers of the corneal epithelium contain
      functional gap junctions, although it appears that intercellular communication in
      the superficial layers does not occur under our control conditions. Intercellular
      communication through these junctions can be altered by various manipulations of
      [Ca2+] and pH.

PMID- 9154383
TI  - Effect of a beta-adrenergic antagonist, propranolol, on induced HSV-1 ocular
      recurrence in latently infected rabbits.
AB  - PURPOSE: Propranolol, a beta-adrenergic antagonist, has been shown to block
      hyperthermically-induced ocular recurrence of HSV-1 in mice and reduce
      spontaneous ocular viral shedding and herpetic corneal lesions in latently
      infected rabbits. The present study was performed to determine the effect of
      propranolol on epinephrine iontophoresis-induced ocular recurrence and
      immunosuppression-induced ocular recurrence in the rabbit eye model. METHODS: New
      Zealand white rabbits were infected with HSV-1 strain 17Syn+ or McKrae. After
      latency was established, the animals were injected intramuscularly with saline
      (placebo), or propranolol (5-200 mg/kg) twice daily, and then induced with
      epinephrine iontophoresis or cyclophosphamide and dexamethasone administration.
      Tear film swabs were cultured to determine the frequency of viral shedding.
      RESULTS: Propranolol administered at a range of doses did not affect the
      frequency or duration of viral shedding following epinephrine or
      cyclophosphamide/dexamethasone induction as compared to saline treatment.
      CONCLUSION: These results demonstrate that propranolol does not significantly
      reduce ocular HSV-1 shedding following induction by epinephrine iontophoresis or
      immunosuppression. By inference, these results suggest two possibilities: (1)
      that viral pathways leading to spontaneous and induced shedding of virus are
      under separate control mechanisms or (2) in rabbits, these inducers are of such
      potency that propranolol is ineffectual.

PMID- 9154384
TI  - Adenovirus infection of the cornea causes histopathologic changes in the lacrimal
      gland.
AB  - PURPOSE: To explore the effects on the lacrimal gland of adenovirus infection of
      the cornea. METHODS: Rabbit corneas were inoculated with human adenoviruses Ad5,
      Ad14, or a rabbit adapted form of Ad 5, and in some instances booster
      inoculations were given. Sections of lacrimal glands removed 21-59 days post
      inoculation were immunostained using antibodies against rabbit Class I and Class
      II MHC molecules, CD4, CD8, CD18, and rabbit thymic lymphocyte antigen (RTLA).
      Relative numbers of positively stained cells were quantified with a Metamorph
      image analysis system. RESULTS: RTLA and CD18 antigens were expressed on many
      interstitial cells in the normal lacrimal gland, but few expressed CD4 or CD8.
      The number of RTLA+ cells increased by 60-100% after inoculation of Ad5 and after
      boosting, and CD18+ cells increased from 33-100% after inoculation of Ad5 and
      after boosting. Booster inoculations also caused focal lymphocytic infiltration.
      MHC Class I was expressed on interstitial cells and duct epithelium, but not
      acinar cells, and there was no detectable difference after viral infection. In
      controls, MHC Class II was localized to a population of interstitial cells and a
      few acinar cells. A single inoculation of the Ad5 virus did not result in an
      increase in the total number of MHC Class II-positive cells at 21 days, but
      inoculation with the rabbit-adapted Ad 5 and booster inoculations caused a 30%
      increase. CONCLUSIONS: Ad5 and rabbit-adapted Ad5 infection of the cornea induce
      lymphocytic infiltration in the lacrimal gland, and the effect is enhanced by
      boosting. There is also an increase in expression of MHC Class II after
      inoculation with rabbit-adapted Ad5 and with booster inoculations.

PMID- 9154385
TI  - Heterogeneous expression of transketolase in ocular tissues.
AB  - PURPOSE: Previous studies have shown that transketolase is preferentially
      expressed in the corneal epithelium and comprises up to 10% of the soluble
      protein of the mature mouse cornea. The aim of this study is to evaluate the
      expression and distribution of TKT in the different ocular tissues. METHODS: We
      have used in situ hybridization and immunohistochemistry to localize TKT mRNA and
      protein in the developing and adult mouse eye. RESULTS: TKT were found to be
      widely distributed throughout the adult mouse eye. Among the ocular tissues
      examined, the corneal epithelium exhibited the highest levels of TKT mRNA and
      protein. Within the epithelial layer, TKT mRNA and protein were differentially
      distributed with the highest expression occurring in basal cells and the lowest
      in apical cells, suggesting that TKT expression in the corneal epithelium may be
      differentiation-related. Enriched expression of TKT was also found in the cornea
      endothelium, lens epithelium, ciliary body, and iris. Low basal levels of
      expression were observed in the limbus and conjunctiva. In contrast to the adult
      eye, TKT expression in the one-day-old mouse eye was homogeneous at low, but
      detectable levels, suggesting that TKT expression is developmentally regulated in
      the cornea as well as in the other ocular tissues. In the healing corneal
      epithelium, TKT expression in the single cell layer of the leading edge was
      completely suppressed until the cells began to stratify, at which point TKT
      expression increased markedly. CONCLUSIONS: The results presented here suggest
      that TKT is differentially expressed and developmentally regulated in the various
      tissues that comprise the eye.

PMID- 9154386
TI  - Immunophenotyping of human dendriform cells from the conjunctival epithelium.
AB  - PURPOSE: Conjunctival Langerhans cells are bone marrow-derived, antigen
      presenting cells that play a major role in the immune response of the ocular
      surface, but they have as yet been little investigated, either functionally or
      phenotypically. This study was undertaken in impression cytology to provide an
      extended immunophenotype of human conjunctival dendriform cells. METHODS:
      Immunostaining procedures were used to seek for the expression of the following
      30 membrane antigens related to the immune system, using dendriform cells
      obtained in conjunctival specimens from 80 normal subjects and 105 with chronic
      conjunctivitis: class II antigens HLADR and DQ, CD1a (T6) and CD5, which usually
      mark Langerhans cells, macrophage markers CD14, CD36 and CD63, various lymphocyte
      antigens (CD2, CD4 and CD8), receptor to interleukin 2 (CD25), adhesion molecules
      and integrins (CD11a, CD11b, CD11c, CD18, CD29, CD41, CD61), the selectin CD62,
      ICAM-1 (CD54), ICAM-3 (CD50) and ELAM-1, CD45RO, related to activation of immune
      cells, and its ligand CD22, receptors to immunoglobulins (CD23 and CD32) and
      complement (CD21), transferrin receptor CD71, tryptase and vimentin, were thus
      investigated. RESULTS: Conjunctival dendriform cells reliably expressed several
      antigens: class II antigens HLA DR and HLA DQ, CD1a, vimentin, CD11a and CD18
      (LFA-1), CD14, CD22, CD36, CD45RO, ICAM-3 and CD63. Other markers were only
      occasionally found (CD4, CD11b, CD29, CD32 and CD54), and the remaining above
      antigens were not expressed. No relevant difference was found between normal and
      inflammatory specimens in the immunophenotype of dendriform cells. CONCLUSIONS:
      This study sheds light on the main antigen-presenting cells of the ocular
      surface. The conjunctival cells share common immunophenotypic features with those
      from skin or mucosae, but our results showed some discrepancies, probably related
      to the specific immune status of the ocular structures.

PMID- 9154387
TI  - Fluorophotometric measurement of pH of human tears in vivo.
AB  - PURPOSE: To measure the pH in the precorneal tear film of humans in vivo using a
      pH-sensitive fluorescent dye, bis-carboxyethyl-carboxyfluorescein (BCECF).
      METHODS: The measurement was initiated by instilling 1 microliter of 2 mM BCECF
      solution into the subject's eye. The pH was calculated by measuring the ratio of
      fluorescent intensities at two excitation wavelengths (490/430 ratio), which was
      dependent on pH, but independent of the dye concentration and other variables.
      The tears of the same subject were then collected and loaded on to a micro pH
      meter to ensure the accuracy of the measurement. RESULTS: The mean pH values of
      40 eyes from 20 healthy volunteers was 7.50 (SD +/- 0.23), which corresponded
      well with those measured by the micro pH-meter. CONCLUSIONS: The method described
      was useful in measuring the pH of the precorneal tear film of humans with minimal
      invasion.

PMID- 9154388
TI  - Morphologic and immunocytochemical characterization of four human uveal cell
      lines (melanoma- and melanocytes-derived).
AB  - PURPOSE: To characterize three cell lines from human uveal melanomas and one
      ocular melanocyte cell line to study the specificity of several antigens in the
      malignant transformation of melanocytic uveal cells. METHODS: Light microscopy
      (LM), transmission electron microscopy (TEM), and immunocytochemical techniques
      were used in the characterization of OCM-1, SP 6.5, and MKT-BR human uveal
      melanoma cell lines and UW-1 normal melanocyte cell line from human uvea. Several
      monoclonal antibodies (MoAbs) S-100, HMB-45, MNF-116, PAL-M1, NK1/C-3, IND-1, and
      MAAMA were used. RESULTS: All cell lines showed an epithelioid/spindle morphology
      with occasional multinucleated cells, and nuclear pleomorphism. TEM showed
      intracytoplasmatic premelanosomes. Incubation with HMB-45 MoAb was positive in
      all cell lines. PAL-M2, NK1/C-3, MAAMA, and IND-1 MoAbs stainings were positive
      with variable intensity. MNF-116 MoAb showed negative staining in the four lines,
      and S-100 MoAb was also negative except for the UW-1 cell line. CONCLUSIONS:
      Human uveal melanoma cell lines OCM-1, SP 6.5, and MKT-BR and the ocular
      melanocyte cell line UW-1 exhibited maintenance of some structural and
      ultrastructural characteristics of melanocytic cells. All four MoAbs, PAL-M2,
      NK1/C3, IND-1, and MAAMA against cutaneous melanoma-associated antigens stained
      positively all melanoma cell lines as well as the melanocytic cell line,
      suggesting that in vitro proliferation of melanocytes could modify their
      antigenic expression.

PMID- 9154389
TI  - Differential effects of HSV-1 and HCMV infection on adhesion molecule expression
      on human corneal keratocytes.
AB  - PURPOSE: Previous studies have shown that keratoplasty buttons obtained at
      surgery from patients with herpes simplex virus-1 (HSV-1) keratitis have elevated
      localized expression of the adhesion molecule ICAM-1, which plays a critical role
      in the initiation and amplification of an immune response. We performed studies
      to determine whether changes in expression of ICAM-1 and HLA class I are direct
      effects of productive infection of human corneal fibroblasts with HSV-1. METHODS:
      Immunocytologic and flow cytometric analyses were performed to analyze the
      ability of HSV-1 to induce ICAM-1 and HLA class I expression in a primary cornea
      derived keratocyte cell line, E-2. Positive controls for these experiments were E
      2 cells infected with human cytomegalovirus (HCMV), which has been shown to
      increase ICAM-1 expression in selected cells, and E-2 cells treated with IFN
      gamma, which upregulates both ICAM-1 and HLA class I expression in most cell
      types. RESULTS: Kinetic cytometric analysis indicated decreased ICAM-1 expression
      3 hours following HSV-1 infection of E-2 cells. In contrast, HCMV led to
      detectable increases in ICAM-1 expression starting 6 hours after infection.
      Infections with either HSV-1 or HCMV resulted in reduced HLA class I expression
      on E-2 and SF cells. CONCLUSIONS: These studies suggest that increased ICAM-1
      expression seen on corneal stromal cells during clinical HSV-1 infection is not a
      direct result of productive viral infection, but of other mechanisms such as
      cytokine release by infiltrating mononuclear cells.

PMID- 9154390
TI  - A novel procedure for the extraction of protein deposits from soft hydrophilic
      contact lenses for analysis.
AB  - PURPOSE: A quick, simple, and efficient extraction technique was developed for
      the removal of protein from soft hydrophilic contact lenses. METHODS: An
      extraction solvent consisting of a 50:50 mix of 0.2% trifluoroacetic acid and
      acetonitrile was used to remove protein from in vitro laboratory-deposited and
      human-worn contact lenses. The protein removed was analyzed using HPLC,
      bicinchoninic acid (BCA) analysis, and SDS-PAGE gel electreophoresis. RESULTS:
      Extraction efficiency for lysozyme from laboratory-deposited Group IV lenses was
      determined to be approximately 100%. Group IV human-worn contact lenses were
      extracted and analyzed for lysozyme by HPLC and total protein by bicinchoninic
      acid (BCA) analysis. Groups I, II, III, and IV contact lenses deposited with an
      artificial tear protein solution and human-worn lenses were extracted and
      analyzed by SDS-PAGE gel electreophoresis and micro-BCA. CONCLUSIONS: The ACN/TFA
      procedure offers a simple, quick, and efficient extraction technique for removal
      of protein from contact lenses for subsequent analysis.

PMID- 9154391
TI  - The lacrimal gland expresses nuclear retinoid X receptors.
AB  - PURPOSE: The lacrimal gland expresses nuclear retinoic acid receptors. This
      suggests that retinoids are involved in control of gene expression in the
      lacrimal gland. Retinoid X receptors (RXRs) form heterodimers with and are
      required for activation of retinoic acid receptors. The purpose of this study was
      to identify retinoid X receptors in the lacrimal gland. METHODS: Total RNA was
      purified from rat, rabbit and human lacrimal glands and from cultured rat
      lacrimal cells. RNA was analyzed by northern blotting using cDNA probes for RXR
      alpha, RXR beta and RXR gamma. Nuclear protein extracts from rat and rabbit
      lacrimal glands were probed for RXR beta by immunoblotting, using a mouse
      monoclonal antibody. RESULTS: RXR alpha mRNA transcripts (5 kb) and RXR beta mRNA
      transcripts (3.3 kb) are present in the lacrimal glands of all species studied
      and in cultured rat lacrimal cells. RXR gamma mRNA (1.9 kb) was detected only in
      the rabbit lacrimal gland. RXR beta is expressed as a 50 kDa protein in rat and
      rabbit lacrimal glands. CONCLUSIONS: This study confirms the presence of RXRs in
      the lacrimal gland, thereby supporting a role for retinoids and their nuclear
      receptors in the control of gene transcription in the lacrimal gland.

PMID- 9154392
TI  - Tinea pedis: clinical experience and efficacy of short treatment.
AB  - Tinea pedis is the commonest fungal infection in developed countries. Topical
      therapy is an accepted and successful method for the management of this
      condition. This has usually involved the application of an antifungal twice or 3
      times a day for 3-4 weeks to achieve a cure rate of > or = 80%. Terbinafine, a
      new antifungal, has been shown in a number of studies to give equally good
      results when applied once or twice daily for 1-2 weeks. In one study, a cure rate
      of 78% was achieved in patients with tinea pedis after a single application of 1%
      terbinafine cream, demonstrating the high potency of this antifungal. Topical
      terbinafine has also been compared to clotrimazole for the treatment of tinea
      pedis. Terbinafine 1% cream applied twice daily for 1 week was significantly
      superior to a 4-week course of clotrimazole 1% cream for treating this common
      mycosis. Overall, the high efficacy of topical terbinafine in treating tinea
      pedis following such-short-duration therapy is undoubtedly due to its fungicidal
      mode of action.

PMID- 9154393
TI  - Onychomycosis--treatment, relapse and re-infection.
AB  - The treatment of onychomycosis has improved considerably following the
      introduction of the oral antifungals terbinafine and itraconazole. The
      pharmacokinetic characteristics of both these drugs has made short treatment
      times effective. Patients with a culture-proven dermatophyte infection of the toe
      nails, receiving terbinafine 250 mg daily for 12 weeks, have a 70% chance of
      cure. The risk of relapse is probably less than 10%, and this may be prevented by
      a further course of terbinafine should the expected increasing length of
      unaffected nail growth stall or cultures become positive. Once cured, the regular
      and prophylactic use of an effective topical antifungal may help to prevent a
      recurrence of tinea pedis and onychomycosis.

PMID- 9154394
TI  - Candida: a review of clinical experience with Lamisil.
AB  - Pharmaceutical companies sometimes quote the MICs of antifungal agents to make
      favourable or unfavourable comparisons with competitor drugs. To the doctor,
      however, the clinical outcome is important. In this light it can be seen that
      topical terbinafine is certainly as effective as, if not more effective than, any
      other anticandidal agent available.

PMID- 9154395
TI  - Tinea corporis/cruris: new treatment options.
AB  - We undertook a prospective, multicentre, double-blind, placebo controlled,
      randomised, parallel-group study to evaluate the efficacy and safety of the
      topical 1% emulsion gel formulation of Lamisil in the treatment of tinea
      corporis/cruris. Eighty-three patients with clinically and mycologically
      confirmed tinea corporis/cruris were enrolled from 6 dermatology practices. Of
      the 62 patients in the intent-to-treat population, 29 were randomised to 1%
      Lamisil emulsion gel (23 male, 6 female; mean age 42 years, range 19-79 years)
      and 33 to placebo (25 male, 8 female; mean age 36 years, range 16-73 years). The
      gels were applied once daily for 1 week. Mycological cure (negative microscopy
      and culture results) and effectiveness of treatment (mycological cure plus no or
      minimal signs and symptoms) were measured on day 7, weeks 2, 4 and 8, and at the
      end of the study. At the study end, rates mycological cure were 83% for Lamisil
      1% emulsion gel and 27% for placebo gel (p < 0.001), with respective rates for
      effective treatment of 83 and 21% (p < 0.001). Complete cure was recorded for 59%
      of patients receiving Lamisil 1% emulsion gel and 13% of patient receiving
      placebo gel (p < 0.001). We conclude that a 1-week course of Lamisil 1% emulsion
      gel is significantly more effective in the treatment of tinea corporis/cruris
      than placebo gel in respect of complete cure, mycological cure and effective
      treatment.

PMID- 9154396
TI  - Pityriasis versicolor: clinical experience with Lamisil cream and Lamisil
      DermGel.
AB  - Pityriasis versicolor is a chronic superficial fungal disease usually located on
      the upper trunk, neck or upper arms. Terbinafine is an orally and topically
      active allylamine antifungal derivative with a broad antifungal spectrum. Several
      studies have documented the high activity of terbinafine (Lamisil) cream in the
      treatment of pityriasis versicolor, with cure rates of 79-100% after 2-4 weeks of
      treatment. Lamisil emulsion gel (Lamisil DermGel) is a new topical formulation
      that remains in the skin in high concentrations for several months after just 1
      week of application. Recently, in a prospective, double-blind, placebo
      controlled, randomised, parallel-group, comparative, multicentre study, we have
      treated patients with pityriasis versicolor with either terbinafine 1% emulsion
      gel (Lamisil DermGel) or placebo gel. Sixty-one patients were included, 31 in the
      Lamisil DermGel group and 30 in the placebo gel group. The gel was applied once
      daily for 7 days and the patients were followed up for 8 weeks. Twenty-eight
      patients in the active and 29 patients in the placebo group were evaluable for
      efficacy. Using the intent-to-treat efficacy analysis, 21/28 (75%) were cured in
      the Lamisil-DermGel-treated group compared to 4/29 (14%) in the placebo group. No
      side-effects were seen. In conclusion, Lamisil DermGel was well tolerated and
      superior to placebo in the treatment of pityriasis versicolor when applied once
      daily for 7 days.

PMID- 9154397
TI  - The efficacy of a topical application of terbinafine 1% solution in subjects with
      pityriasis versicolor: a placebo-controlled study.
AB  - A prospective randomised placebo-controlled double-blind study was designed to
      investigate whether topical terbinafine 1% solution is an effective treatment for
      subjects with pityriasis versicolor. The intention-to-treat population consisted
      of 110 subjects. The number of subjects who received terbinafine 1% solution was
      76 and the number who received placebo was 34; treatments were given twice a day
      for 1 week. The primary efficacy variables were categorised at weeks 1, 2, 4 and
      8. Eight weeks after the start of therapy, 81% of the subjects using terbinafine
      solution and 41% of those receiving placebo had a negative mycological
      examination (p < 0.001). A clinical effect of treatment was recorded in 72% of
      the subjects using terbinafine 1% solution and 26% of those receiving placebo (p
      < 0.001). We conclude that terbinafine 1% solution is an effective and safe local
      treatment modality for pityriasis versicolor.

PMID- 9154398
TI  - Effect of Lamisil and azole antifungals in experimental nail infection.
AB  - Onychomycosis is primarily caused by dermatophyte fungi but occasionally by
      yeasts and non-dermatophytic moulds. The aim of this study was to develop an in
      vitro model of nail invasion by dermatophytes, yeasts and non-dermatophytic
      moulds, and to provide an alternative system for studying the activity of
      different classes of antifungal drugs against fungi associated with
      onychomycosis. In the absence of extraneous nutrients, Trichophyton
      mentagrophytes was seen in electron microscopy to degrade completely healthy nail
      plate. Candida albicans germinated on nail fragments, but invasion of the nail
      plate was not seen. The mould Fusarium formed long channels through the matrix of
      the nail plate. Aspergillus versicolor appeared to penetrate the outer and
      intermediate surface of the nail plate only. Acremonium sp. and Scopulariopsis
      brevicaulis did not invade nail in this model. Exposure of nail fragments to
      terbinafine (0.25 mg/l for 3 h) inhibited invasion by T. mentagrophytes, C.
      albicans and the non-dermatophytic moulds. Itraconazole (0.25 mg/l for 3 h)
      prevented nail plate invasion by T. mentagrophytes, A. versicolor and Fusarium
      but did not totally inhibit the surface growth of Acremonium or S. brevicaulis.
      C. albicans grew in the presence of itraconazole. The results indicate that
      terbinafine is readily absorbed by the nail and that the drug is bio-available in
      nail keratin. A short exposure of nail to low concentrations of terbinafine acted
      as a barrier against fungal invasion. Itraconazole appeared to be effective
      against Trichophyton and some non-dermatophytic moulds.

PMID- 9154399
TI  - Epidemiology and ecology of onychomycosis.
AB  - The epidemiology and ecology of onychomycosis are complex and little understood.
      Most is known about tinea unguium, dermatophytic nail infection, and its
      causative agents. This is often categorised according to the precise locus on the
      nail of the infection. The principal infectious propagules are thought to be the
      arthroconidia or chlamydospores which form within the solid substratum of invaded
      nail tissue. The process of infecting new hosts appears to be facilitated by
      abrasion, moistening and scratching. The role of the non-dermatophyte yeast
      Candida as an agent of onychomycosis per se may have been overestimated. The
      range of interactions between dermatophytes and non-dermatophytes in nails is
      complex and poorly understood. There may be at least six distinct ecological
      categories of non-dermatophyte isolations from nails. It would be of clinical
      interest to know which species found in mixed infections were never able to
      advance beyond 'secondary colonisation', as they would not require specific
      treatment.

PMID- 9154400
TI  - Oral terbinafine (Lamisil) in the treatment of fungal infections of the skin and
      nails.
AB  - The efficacy and safety of antifungal drugs depend upon their mode of action, the
      minimal inhibitory concentration (MIC) and its relationship to the minimal
      fungicidal concentration (MFC), the spectrum of activity and drug kinetics at the
      involved site. Terbinafine acts at the fungal cell wall. Its MIC against
      dermatophytes is the lowest of all currently available systemic antifungal
      agents. It is the only one with an MIC:MFC ratio of 1:1 so that terbinafine
      should be effective over very short treatment durations in dermatophyte
      infections of the scalp, palms and soles, and nail, providing that drug
      penetration is adequate, as it appears to be. Therapeutic levels persist for a
      considerable period after the cessation of treatment, also favouring short
      duration therapy. Terbinafine is effective against all varieties of dermatophyte.
      Terbinafine given over 4 weeks or less is effective against Trichophyton of the
      scalp in children and adults. Its efficacy in zoophilic ectrothrix infection is
      anecdotal, but it is likely on theoretical grounds. Terbinafine is also effective
      against pityriasis versicolor and vaginal candidosis, but only topically. As of
      March 1996, around 3,000,000 patients have been treated worldwide with
      terbinafine, mostly for 12 weeks for toe-nail onychomycosis. Gastro-intestinal
      disturbance and minor skin rashes are seen in 5 and 2% of patients, respectively.

PMID- 9154401
TI  - Significance of non-dermatophyte moulds and yeasts in onychomycosis.
AB  - In a multicentre, randomised, double-blind, 48-week clinical trial, 118 patients
      with toe-nail onychomycosis were given terbinafine (250 mg daily) or placebo for
      12 weeks, followed by 12 weeks of observation. Non-responders were offered 12
      further weeks of terbinafine (250 mg daily) from week 28. Each patient had 8-12
      consecutive nail specimens collected from the same nail, allowing for an
      assessment of the fungal nail flora from 1,321 nail specimens. By week 48, the
      overall mycological cure rate for terbinafine patients was 94%. 64% of patients
      had an underlying dermatophyte infection with at least 1 non-dermatophyte mould
      or yeast isolated from at least 1 specimen. These contaminants often overgrow or
      mask the presence of a dermatophyte. In only 2.5% of all patients was the same
      non-dermatophyte isolated from 2 or more consecutive specimens, probably
      representing secondary colonisation which exploits nutrients released by the
      underlying dermatophyte. The presence of incidental non-dermatophyte contaminants
      or secondary colonisers did not affect treatment outcome, and in this study
      treatment of the primary dermatophyte pathogen with terbinafine cleared the nails
      from infection in all cases. 80% of patients remained mycologically negative
      after 2 years.

PMID- 9154402
TI  - The use of oral terbinafine (Lamisil) in children.
AB  - In an ongoing study of Lamisil in children, 21 patients have so far been enrolled
      and preliminary data are reported in this paper. Eighteen have tinea capitis and
      1 has tinea corporis. So far, Trichophyton tonsurans has been identified in 17
      and Trichophyton violaceum in 2. Lamisil has so far proved to be well tolerated,
      efficacious and cost-effective in a 2-week course in those children with a
      Trichophyton species. If Microsporum canis is isolated, a longer course is
      probably indicated. Lamisil has the distinct advantage of producing good results
      in a short time period, making patient compliance less of a problem.

PMID- 9154403
TI  - Controversies in medical mycology.
AB  - Questions and controversies involving many aspects of medical mycology have
      increased in recent years. Case histories are described in which fungal infection
      causes unexpected and atypical problems. Molecular techniques of diagnosis need
      to be used alongside traditional culture methods. Increased drug use has led to
      genuine concerns and differing views regarding the definition and development of
      resistance by fungi. The use and value of combinational antifungal therapy and
      the employment of immunomodulatory agents concomitant with antimycotics have been
      debated. Nonetheless, good standards have been developed in the testing of
      antifungal agents. These, together with the commercial viability of antifungal
      drugs and hence increased interest in their development, mean that although we
      have entered the golden age of mycology we have also entered the golden age of
      antifungal therapy.

PMID- 9154404
TI  - Recovery of nosocomial fecal flora from frozen stool specimens and rectal swabs:
      comparison of preservatives for epidemiological studies.
AB  - The recovery of antibiotic-susceptible and -resistant aerobic Gram-negative
      bacilli from stool specimens and from mock rectal swabs after freezing (-20
      degrees C) for as long as 4 weeks was studied using three preservatives: Cary
      Blair (CB) transport medium, buffered glycerol saline (BGS), and Para Pak C&S
      solution (CS). In addition, the recovery of enterococci from rectal swabs was
      investigated after storage of swabs in Stuart's transport media at 4 degrees C as
      long as 4 weeks. The log10 decreases in bacterial counts from seeded stool
      suspensions frozen in BGS were 0.64 (i.e., fourfold) and 1.16 after 1 and 4
      weeks, respectively, which were significantly less (p < .05) than 1 and 4 week
      decreases following freezing in CB (1.57 and 2.85) or in CS (1.50 and 2.45). The
      recovery of Gram-negative bacilli from patients' rectal swabs preserved in BGS
      was consistent with the results of the experiments with seeded stool suspensions.
      There was no detectable decrease in recovery of enterococci from rectal swabs
      stored at 4 degrees C. BGS performed well as a preservative for freezing stool
      specimens or rectal swabs for later recovery of nosocomial Gram-negative bacilli;
      enterococci survived well in refrigerated rectal swab specimens.

PMID- 9154405
TI  - Comparison of biological and chemical assays for the quantitation of rifapentine
      in human plasma.
AB  - The purpose of this study was to establish the correlation between biological and
      chemical assays for the quantification of rifapentine in human plasma. The
      bioassay was found to overestimate antibiotic plasma concentration when compared
      to the high-performance liquid chromatography (HPLC) assay for rifapentine (r =
      0.9538, n = 220). This was because of the presence of varying amounts of the
      biologically active 25-O-desacetyl metabolite in the test samples. A better
      correlation (r = 0.9804, n = 220) was observed when the bioassay data were
      compared to combined parent-metabolite HPLC values. Such correlative data are
      necessary adjuncts in the establishment of antibiotic susceptibility test
      breakpoints.

PMID- 9154406
TI  - Evaluation of the Roche AMPLICOR MTB assay for the detection of Mycobacterium
      tuberculosis in sputum specimens from prison inmates.
AB  - The reliability of the Roche Mycobacterium tuberculosis polymerase chain reaction
      (PCR) assay (AMPLICOR MTB) for the diagnosis of pulmonary tuberculosis was
      evaluated by testing expectorated sputum specimens from 187 inmates in Texas
      state prisons and comparing the results to culture and medical history. Of the 80
      specimens that were culture positive for mycobacteria, 36 specimens from 16
      patients grew M. tuberculosis. Forty-six specimens were smear positive for acid
      fast bacilli (AFB), and of these, M. tuberculosis was isolated from 24. On
      initial testing, 52 specimens were PCR positive. Thirty-one of these 52 were
      culture positive for M. tuberculosis, and 21 were culture negative, resulting in
      a PCR sensitivity and specificity of 86.1 and 96.1%, respectively. After
      resolving discrepancies by review of the medical history and repeat testing, PCR
      sensitivity, specificity, and positive and negative predictive values,
      respectively, were 92.8, 99.8, 98.1, and 99.2%. For AFB smear-positive specimens,
      the sensitivity, specificity, and positive and negative predictive values, were
      95.8, 100, 100, and 93.3, respectively; whereas, for AFB smear-negative
      specimens, these values were 87.5, 99.7, 95.5, and 99.4%, respectively. These
      results confirm the reliability of the AMPLICOR MTB assay for direct detection of
      M. tuberculosis in AFB smear-positive sputum specimens and suggest a potential
      role in evaluating AFB smear-negative sputum specimens.

PMID- 9154407
TI  - Evaluation of the Etest for detection of tetracycline resistance in Mycoplasma
      hominis.
AB  - The Etest was compared with microbroth dilution for performing in vitro
      susceptibility tests in 38 isolates of Mycoplasma hominis chosen to represent a
      wide range of MIC values. MIC50s were 4 micrograms/ml for both methods; whereas,
      MIC90s were 64 and > 256 micrograms/ml for broth and Etest, respectively. Etest
      MICs determined on SP 4 agar were usually two or more dilutions greater than
      microbroth MICs in SP 4 broth, and values were prone to change by one to two
      dilutions when different inoculum densities were used. Inocula of 10(5) to 10(6)
      color-changing units/ml gave the most consistently readable MICs, with discrete
      colony formation surrounding the ellipse. Etest MICs for 5 isolates tested a
      second time at the same inoculum on SP 4 agar agreed with the original value
      within 1 dilution. For 12 isolates tested on A 8 agar simultaneously with SP 4
      agar, MICs for 10/12 agreed within one dilution; whereas, in the other 2
      isolates, MICs varied by two dilutions. These findings suggest that the Etest,
      when properly controlled, can be used to determine tetracycline MICs for M.
      hominis.

PMID- 9154408
TI  - Susceptibility of beta-hemolytic streptococci to nine antimicrobial agents among
      four medical centers in Salt Lake City, Utah, USA.
AB  - A multicenter study was performed to evaluate the susceptibility of beta
      hemolytic streptococci to nine antimicrobial agents. MICs were performed in
      cation-supplemented Mueller-Hinton broth with 3.5% lysed sheep red blood cells
      according to NCCLS guidelines. A total of 646 isolates were tested: 300 (46%)
      group A; 170 (26%) group B; 38 (6%) group C, 35 (5%) group F; 83 (17%) group G;
      and 20 (3%) nongroupable. Six percent of the total isolates were resistant to one
      or more of the antibiotics tested. Approximately 7% of 387 strains from the
      University of Utah Hospital and Clinics were resistant to erythromycin. Four
      isolates were resistant to clindamycin. Six strains (3%) from Primary Children's
      Medical Center (207 tested) were resistant to one or more of the macrolides.
      Resistance was rare at the LDS Hospital and the Salt Lake Veteran's Affairs
      Hospital. Overall, resistance among beta-hemolytic streptococci in this
      geographic location does not seem to be a significant problem, except at the
      tertiary care university hospital.

PMID- 9154409
TI  - Antimicrobial characteristics of quinupristin/dalfopristin (Synercid at 30:70
      ratio) compared to alternative ratios for in vitro testing.
AB  - Quinupristin/dalfopristin is a new streptogramin combination that occurs at a
      natural ratio and formulation of 30:70. Rapid metabolism of the dalfopristin
      component to RP 12536 in vivo puts in question the validity of in vitro test of
      spectrum with the parent combination. In studies of quinupristin with both
      dalfopristin and RP 12536, a wide range of ratios (30:70, 50:50, 70:30) were
      tested by reference MIC and MBC tests. No significant potency differences were
      observed between combination ratios or metabolic components when testing 256
      bacterial strains. Quinupristin/dalfopristin or quinupristin/RP 12536 remained
      active, by bactericidal action against many staphylococci and Streptococcus ssp.
      Enterococcus faecium strains were susceptible (MIC90, 2 micrograms/ml; static
      effect only) to the streptogramin, but E. faecalis, Pasteurella multocida,
      Pediococcus ssp., Haemophilus influenzae, and Bacteroides fragilis were generally
      less susceptible (MIC90, > or = 8 micrograms/ml). The log phase inoculum was
      preferred for MBC and kill-curve tests with this combination. The 30:70 ratio in
      vitro susceptibility test of quinupristin/dalfopristin as used to date, seems to
      predict the potency and spectrum of this streptogramin accurately and all
      clinically important in vivo ratios of the injectable form or its major
      metabolites. Quinupristin/dalfopristin should be further investigated for
      clinical use against emerging resistant Gram-positive infections, especially
      penicillin-resistant streptococci and glycopeptide-resistant E. faecium that
      exhibit susceptibility in this investigation.

PMID- 9154410
TI  - Influence of pH on the antimicrobial activity of clarithromycin and 14
      hydroxyclarithromycin against Haemophilus influenzae using an in vitro
      pharmacodynamic model.
AB  - Clarithromycin activity can be influenced by the pH of the surrounding
      environment. Evidence supports a reduced pH of middle ear fluid (MEF) and lung
      tissues in patients with otitis media and pneumonia, respectively. To evaluate
      the influence of pH on clarithromycin activity, an in vitro pharmacodynamic
      chamber model (PDCM) was used to generate bacterial time-kill curves for
      clarithromycin and a 2:1 ratio of clarithromycin and 14-hydroxyclarithromycin
      (HC) against Haemophilus influenzae at three different pH values: 7.2, 6.8, 6.4.
      Concentrations observed in MEF and lung tissues were simulated for clarithromycin
      alone and clarithromycin plus HC. Differences in activity at each pH were
      identified by comparing initial kill curve slopes and total log reduction.
      Experiments with amoxicillin-clavulanate were conducted as a reference. In
      simulated MEF regimens at pH 7.2, activity of clarithromycin alone improved by
      adding HC (additional 2 log10 reduction at 8 h); however, at pH values of 6.8 and
      6.4, kill curves resembled growth controls. In simulated lung regimens,
      differences between clarithromycin alone and clarithromycin plus HC were
      insignificant; both produced a 2 log10 reduction at pH 7.2, and activity
      dramatically dropped to < 0.4 log10 as pH declined. In contrast, amoxicillin
      clavulanate consistently produced a 3 log10 reduction over each pH value with
      more rapid initial kill relative to all clarithromycin regimens. These findings
      suggest the activity of clarithromycin against H. influenzae may be significantly
      compromised in respiratory tract infections involving a reduced pH. Trials with
      emphasis on clinical outcomes analysis will assist further in determining the
      significance of these experimental findings.

PMID- 9154411
TI  - Mycobacterium avium complex endocarditis: spurious diagnosis resulting from
      laboratory cross contamination.
AB  - Contamination between specimens within clinical microbiology laboratories may be
      responsible for spurious outbreaks of mycobacterial infections. We report the
      case of a patient who had culture-negative endocarditis and whose cardiac tissue
      obtained at surgery yielded Mycobacterium avium complex (MAC). Epidemiologic
      investigation suggested cross contamination probably occurred during processing
      of the sputum specimens of a patient with pulmonary MAC disease and the cardiac
      samples from our patient; molecular strain typing showed the isolates from both
      patients to be identical. When mycobacterial infection rates increase or an
      unexpected case of mycobacterial infection occurs, the clinician should be alert
      to the possibility of cross contamination in the laboratory as a possible
      explanation.

PMID- 9154412
TI  - In vitro evaluation of contemporary beta-lactam drugs tested against viridans
      group and beta-haemolytic streptococci.
AB  - Streptococci continue to be prevalent causes of mild as well as of serious, life
      threatening infections. Furthermore, some species harbor antimicrobial
      resistances (pneumococcus, viridans gr. streptococci) that compromise effective
      chemotherapy with beta-lactam drugs or other antimicrobial classes. In this
      study, the potency and spectrum of 12 beta-lactams was assessed versus 274
      contemporary isolates of viridans group and beta-haemolytic streptococci using
      reference methods. Cefotaxime and ceftriaxone (MIC90s, 0.015 to 2 micrograms/ml,
      84 to 100% susceptible) were consistently most potent among the agents tested.
      Ceftazidime (MIC90s, 0.25 to 8 micrograms/ml) and ticarcillin (MIC90s, 0.5 to >
      32 micrograms/ml) were least active among the cephalosporins and penicillins,
      respectively. When 25% pooled serum was added to the reference test medium,
      ceftriaxone activity decreased fourfold, and cefotaxime remained highly active.
      As penicillin/beta-lactam-resistant streptococci with altered penicillin-binding
      protein target sites become more prevalent, only a few "third-generation" cephems
      seem to have sustained activity when used alone or possibly with a carefully
      selected co-drug. Routine testing of these species against beta-lactams and
      alternative drugs should be encouraged to detect emerging resistance patterns.

PMID- 9154413
TI  - Prediction of the outcome of growth at 2 years of age in neonates with intra
      uterine growth retardation.
AB  - The aim of the study was to identify at birth, in infants showing intra-uterine
      growth retardation (IUGR), any parameters correlative with the increase in height
      SDS during the first 2 years of life and with short stature at 2 years of age,
      and to determine whether the sensitivity and specificity of such parameters would
      permit their use as predictors of short stature at 2 years of age. Two cohorts of
      children born with IUGR with birth weight < 3rd percentile, were studied. In the
      first group of 317 children selected at birth, 224 were effectively followed up
      to 2 years of age (group 1) and the second group of 48 children was evaluated at
      2 years of age for short stature related to IUGR (group 2). Perinatal history,
      auxological data at birth and parental height were monitored in a prospective
      study for the group 1 children and in a retrospective study for the group 2
      children. By 2 years of age, 8% of the 224 children followed (group 1), presented
      short stature (< or = 2 SDS). In a multiple linear regression model, gestational
      age, birth length (SDS), target height (SDS) and maternal tobacco consumption
      were found to be the strongest predictors of the magnitude of the height gain
      (SDS) during the first 2 years of life. Using these parameters 47% of the
      variability of the height gain (SDS) during the first 2 years of life could be
      explained at birth. Moreover, logistic regression analysis showed three risk
      factors at birth for short stature by 2 years of age: reduced gestational age due
      to premature birth (adjusted odd ratio (O.R.) = 2.10; 95% C.I. = 1.06-4.14), the
      greater the difference (for each S.D.) between birth length (SDS) and target
      height (SDS) (O.R. = 1.93; 95% C.I. = 1.40-2.66) and although as a borderline
      significant factor, maternal tobacco consumption (O.R. = 1.58; C.I. 95% = 0.81
      3.07). Non-parametric discriminant analysis was used to investigate whether short
      (< or = -2 SDS) or normal stature (> -2 SDS) at 2 years could be predicted at
      birth using gestational age (weeks), birth length (SDS), target height (SDS) and
      maternal tobacco consumption as discriminant variables. We found that this
      discriminant model correctly predicted at birth the short stature of 57 of 59
      children at 2 years of age (sensitivity 97%) and the normal stature of 142 of 159
      children at 2 years of age (specificity 89%). In conclusion, an accurate
      prediction of short stature by 2 years of age is feasible at birth in the IUGR
      neonate.

PMID- 9154414
TI  - Development of the human principal sensory trigeminal nucleus: a morphometric
      analysis.
AB  - The anatomical development of the principal sensory trigeminal nucleus was
      assessed with morphometric features using serial celloidin sections of 15 human
      brains, including 12 brains obtained from fetuses and neonates. A microscope and
      an optical electronic planimeter combined with a computer were employed for
      morphometric measurements of columnar areas, neuronal numbers, neuronal areas and
      neuronal perimeters to statistically analyze and evaluate the development of
      neuronal densities, neuropil indexes and circularity ratios. We could not detect
      the principal sensory trigeminal nucleus in the specimen of 12 gestational weeks
      (GW). Microscopic observation disclosed that the fetal principal sensory
      trigeminal neurons approached those of the adult around 33 GW in terms of cell
      arrangements, amounts of Nissl bodies and morphology of neurons. Our morphometric
      analysis showed that the columnar volume, the neuronal area and the neuropil
      index increased with gestational age. The neuronal density decreased with
      gestational age, especially from 16 to 32 GW. Comparing the neuronal area with
      the columnar volume, it developed before the columnar volume during the fetal
      period. The neurons of the principal sensory trigeminal nucleus matured around 33
      GW under microscopic observation and in terms of the distribution of neuronal
      areas. The development of the neuropil may accelerate after individual neurons of
      principal sensory trigeminal nucleus mature.

PMID- 9154415
TI  - The effects of maternal exercise on fetal heart rate and movement patterns.
AB  - The aim of this study was to investigate the effects of maternal exercise on
      fetal movement and heart rate patterns. Twelve healthy women at 29-32 weeks of
      pregnancy performed a (sub)maximal bicycle exercise test, reaching 53-99% (median
      82%) of their maximal increase in heart rate (MIHR). Fetal heart rate (FHR) and
      its variation and fetal body and breathing movements were recorded for 1 h before
      and after the exercise and also on a control day. After exercise, FHR was higher
      for 30 min and FHR variation reduced for 20 min as compared with pre-exercise
      levels (P < 0.01). Fetal body movements were reduced for the first 5 min
      following exercise (P < 0.05). In two cases, fetal bradycardia was observed (at
      89 and 99% MIHR) followed by a considerable reduction in FHR variation and
      absence of body and breathing movements for 20 min. In the other 10 fetuses fetal
      breathing activity was increased for the first 5 min after exercise (P < 0.05).
      FHR (and to a lesser extent breathing movements) increased with increasing level
      of maternal exercise, but decreased when the % MIHR exceeded approximately 90%.
      Body movements were negatively correlated with the % MIHR (P < 0.05). In
      conclusion, moderate to heavy maternal exercise clearly affects the human fetus
      with signs of transient fetal impairment after heavy exercise.

PMID- 9154416
TI  - Stereology of the myocardium in human foetuses.
AB  - The rate of cellular proliferation and hypertrophy of the cardiac myocytes in the
      human perinatal period is still controversial. This work uses stereology to
      evaluate the prenatal quantitative changes of the myocardium. The hearts of 36
      human foetuses, ranging from the 2nd trimester to the 3rd trimester, were
      studied. Fifteen random microscopic fields were analyzed in each heart. The
      following stereological parameters were determined: Vv[myocyte] and
      Vv[interstitium] (the volume densities of the cardiac myocyte and interstitium,
      respectively) and the Nv[myocyte] (the numerical density of the cardiac
      myocytes). The total number of myocytes (N[myocyte]) and the mean myocyte volume
      (V[myocyte]) were also determined. All differences between the second and the
      third trimester of gestation, tested with the Mann-Whitney test, were
      statistically significant (P < 0.05). The Vv[myocyte] decreased 8.69% and the
      Vv[interstitium] increased 49.83% in this period. Simultaneously, the Nv[myocyte]
      decreased 16.64%, the V[myocyte] increased 16.39%, the cardiac weight increased
      366.67% and the N[myocyte] increased 272.06%. In conclusion, during the last two
      gestational trimesters the human heart increases in weight more than 4.5 times,
      the volume density of myocytes decreases while the volume density of the cardiac
      interstitium increases. The numerical density of myocytes per myocardium volume
      decreases but the myocytes became greater in mean volume (more than 16%).

PMID- 9154417
TI  - Primitive reflexes and the determination of fetal presentation at birth.
AB  - Ninety term breech-presenting singletons with birth weights greater than 2500 g
      and no congenital anomalies were matched with similar cephalic-presenting infants
      on gender and mode of delivery (n = 180). Thirteen primitive reflexes were
      examined at birth, 6 weeks and 3 and 5 months. No significant differences in the
      intensity of the asymmetrical tonic neck, symmetrical tonic neck, positive
      support tonic labyrinthine (prone and supine), segmental rolling (head-on-body
      and body-on-body), Galant, Moro, upper and lower extremity grasp, lower extremity
      placing and stepping reflexes were observed between these two groups of infants.
      Infants delivered vaginally, regardless of presentation, had weaker Moro reflexes
      at 5 months than infants delivered by cesarean section. The popular notion that
      precursors to early motor behaviors, such as the placing and stepping reflexes,
      are determinants of fetal presentation at the end of pregnancy is not supported
      by these results. Instead, spontaneously generated active whole body movements
      may be more significant influences of fetal orientation at the time of birth.

PMID- 9154419
TI  - Partnerships buffer and strengthen.

PMID- 9154418
TI  - Failure to screen newborns for inborn disorders: a potential consequence of
      changes in newborn care.
AB  - OBJECTIVES: To determine how changes in the structure of the hospital care of
      infants, such as shortened post-natal stays, affect the completeness of newborn
      screening. DESIGN: Cohort. SETTING: Two large maternity hospitals. PARTICIPANTS:
      8751 consecutive births at the study hospitals during 1993. MAIN OUTCOME MEASURE:
      The completeness of initial specimen collection and processing as determined by
      matching of birth and screening records. RESULTS: At least one specimen was
      received by the screening program for 8675 (99.1%) of the births. Most non
      screened patients (71/76, 93%) had been admitted to the neonatal intensive care
      unit (NICU). Of these, 53/71 (75%) were low birth weight infants who died within
      48 h of birth. Even after excluding these non-survivors, NICU patients were 37
      times more likely to be unscreened than their healthy counterparts (22 vs. 0.6
      per 1000 infants, 95% C.I. 12.8, 92.8 P < 0.01). A common characteristic of non
      screened NICU survivors, (12/18) was interhospital transfer for sub-specialty
      care. Among patients in the healthy-baby nursery, early discharge (i.e. < 24 h of
      age) accounted for 2/5 (40%) of the cases of non-screening. The non-screening
      rate among patients discharged early was 25 times higher than for those
      discharged after 24 h (9.8 vs. 0.4 per 1000 infants, 95% C.I. 4.2, 149 P < 0.01).
      CONCLUSIONS: Although the overall rate of screening was high, NICU patients,
      especially those requiring transfer, are disproportionately at risk for non
      screening. Early discharge of healthy newborns was also significantly associated
      with non-screening. This latter finding is of special importance given the
      current trend toward shorter hospital stays for newborns. Increased attention to
      ensuring the collection of specimens from these two high-risk populations is
      warranted.

PMID- 9154420
TI  - Delivery of home care services after discharge: what really happens.
AB  - Social workers in hospitals develop discharge plans for in-home patient care with
      little systematic feedback about postdischarge implementation. A telephone follow
      up study of patients discharged from an urban teaching hospital in 1990 was
      undertaken to determine the extent to which discharge plans for home services
      were carried out and to identify factors associated with unsuccessful
      implementation. Overall, 72 percent of the patients received all, 19 percent
      some, and 9 percent none of the planned home care services. Great variability was
      found in service delivery: Registered nurse visits were the most successfully
      delivered type of service; 24-hour companions were the least successfully
      delivered service. Further, over one-third of patients experienced termination or
      reduction of services between discharge and the follow-up interview 21 to 28 days
      after discharge. Such unexpected and varied outcomes suggest the need for
      development of discharge follow-up programs that move beyond hospital walls to
      ensure that patients receive needed services.

PMID- 9154421
TI  - Effect of predischarge interventions on aftercare attendance: process and
      outcome.
AB  - A widely recognized problem in the mental health services delivery system is that
      of patients' early discontinuance of therapy. But less attention has been given
      to the high rate of nonattendance at initial appointments in outpatient mental
      health settings. The purpose of the study discussed in this article was to
      determine if particular predischarge interventions had an effect on whether
      psychiatric patients attended their initial aftercare appointments at a Veterans
      Administration mental health clinic. Two groups of patients were given
      predischarge interventions and one was not (a control group). Results showed a
      trend of greater attendance at initial aftercare appointments by those who
      received a predischarge intervention; however, the differences were not
      statistically significant. Suggestions for clinicians and researchers are
      provided.

PMID- 9154422
TI  - Differential work assignments of social work practitioners in hospitals.
AB  - This article reports the results of a survey concerning the differential
      assignment of tasks to social workers with bachelor of social work (BSW) and
      master of social work (MSW) degrees by social work directors in Canadian
      hospitals. It also provides data relative to the variation in amount of
      supervision provided to workers in those settings where both BSW-level and MSW
      level workers perform the same tasks. It is intended that this study will yield
      useful information to assist the profession in defining the appropriate
      assignment of tasks to hospital social workers.

PMID- 9154423
TI  - Relocation to a new environment: decisional control and the move to a nursing
      home.
AB  - Bivariate and multivariate analyses were used to study the effect of deciding to
      move and wanting to move to a nursing home on the initial reactions of 502
      elderly residents to their new environment. Data used in the analysis were taken
      from the Geriatric Nurse Practitioner Project in which residents were interviewed
      within one month of admission. Three scales were used to measure initial
      reaction: participation in nursing home activities, satisfaction with services,
      and social interaction. Covariates used to control for differences between groups
      were age, activities of daily living score, cognitive score, and affective status
      score. Bivariate relationships were found between the independent variables,
      deciding to move and wanting to move, and two measures, satisfaction with
      services and participation in nursing home activities. Multivariate analysis
      suggests that the two variables independently influence satisfaction and
      participation. Implications for practice and further research are discussed.

PMID- 9154424
TI  - Services for infants and toddlers with disabilities: IDEA, Part H.
AB  - In October 1986 P.L. 99-457, the Education of the Handicapped Act Amendments of
      1986, was enacted. Part H of this legislation obligates participating states to
      provide early intervention services to children with developmental disabilities
      from birth up to their third birthday. This act has since been renamed the
      Individuals with Disabilities Education Act. All states are now planning to
      implement this act through the development of multidisciplinary, comprehensive
      service delivery systems, and social workers in health care settings will play a
      critical role in the identification, referral, and case management of services
      for the affected population. This article describes the mandates of this
      legislation and defines the social worker's role.

PMID- 9154425
TI  - Heart disease and associated risk factors among Hawaiians: culturally responsive
      strategies.
AB  - The incidence of heart disease is disproportionately large among the Hawaiian
      population. This article discusses the prevalence of heart disease and associated
      risk factors among Hawaiians and identifies barriers to health care, including
      accessibility and the acceptability of services to this population. Case examples
      are provided. Culturally responsive strategies to address these problems are
      described, and implications for social work are discussed.

PMID- 9154426
TI  - Intimacy, loneliness, and openness to feelings in adult children of alcoholics.
AB  - This article examines whether adult children of alcoholics (ACAs) have more
      problems with intimacy, loneliness, and openness to their own feelings than adult
      children of nonalcoholics (ACNAs). A sample of 76 adults ages 25 to 40 was drawn
      from the membership of a church. No subjects were preidentified as being ACAs.
      Subjects completed an 89-item questionnaire that included four standardized
      instruments. ACAs were found to be experiencing significantly less intimacy in
      their closest current relationship than ACNAs. Significant associations were
      found among the major variables of intimacy, loneliness, and openness to
      feelings, although correlations were much stronger for ACNAs, suggesting
      different relationships among the variables for the two groups. Models for the
      prediction of intimacy and loneliness were constructed in which a significant
      amount of the variance for both variables was predicted.

PMID- 9154427
TI  - Developing a research unit within a hospital social work department.
AB  - This article describes the establishment of a research unit as an integral part
      of a hospital social work department on the basis of the authors' experience in a
      cancer center over a 13-year period. Methods are described for building support
      within the institution, for the process of initiating the unit, for deciding on
      study topics, and finally for bridging the gap between clinical and research
      staff. The evolution of the relationship between clinical and research staff was
      characterized by four different phases: curiosity, competitiveness, cooperation,
      and collaboration. A childhood bereavement project is used to exemplify the
      developmental processes and the ongoing interaction of research and clinical
      staff. The professional practice of all staff benefited from the increased
      academic rigor and productivity, although some staff remained unconvinced of the
      value of such a major research effort. The benefits and costs of the unit are
      also discussed.

PMID- 9154428
TI  - Naive, not stupid.

PMID- 9154429
TI  - Addressing AIDS long-term care issues through education and advocacy.

PMID- 9154430
TI  - Testosterone levels and evoked vocal responses in a natural population of the
      frog Batrachyla taeniata.
AB  - Relationships between testosterone plasma levels and evoked vocal responses of
      males of the leptodactylid frog Batrachyla taeniata from southern Chile were
      studied. Evoked vocal responses were elicited in the field with playbacks of a
      synthetic imitation of the conspecific advertisement call and variants of this
      signal for which different temporal parameters were modified. Testosterone plasma
      levels were measured with radioimmunoassay in blood samples obtained from the
      experimental subjects immediately after the playback experiments and from
      nonstimulated males. Testosterone levels between groups did not differ
      significantly. A significant correlation between testosterone concentration and
      number of calls given in response to the synthetic advertisement call was found.
      Testosterone levels were also significantly correlated with the total number of
      calls given by the experimental subjects in response to the complete series of
      stimuli. Other measures of evoked vocal responses, i.e., number of pulses per
      call, call duration, pulse rate, and latency to first call, were not
      significantly correlated with testosterone levels. These results indicate a
      predominant effect of testosterone on the motivation of males of B. taeniata to
      call, rather than on the physical attributes of the vocalizations.

PMID- 9154431
TI  - Androgen-behavior correlations in hypogonadal men and eugonadal men. I. Mood and
      response to auditory sexual stimuli.
AB  - Mood and response to auditory sexual stimuli were assessed in 33 hypogonadal men
      receiving testosterone (T) replacement therapy, 10 eugonadal men receiving T in a
      male contraceptive clinical trial, and 19 eugonadal men not administered T. Prior
      to and after 6 weeks of hormone administration, men completed a mood
      questionnaire, rated sexual arousal to and sexual enjoyment of auditory sexual
      stimuli, and performed a dichotic listening task measuring selective attention
      for sexual stimuli. Mood questionnaire results suggest that T has positive
      effects on mood in hypogonadal men when hormone levels are well below the normal
      male range of values, but does not have any effects on mood when hormone levels
      are within or above the normal range. However, increased sexual arousal and
      sexual enjoyment were associated with T administration regardless of gonadal
      status. Eugonadal men administered T also increased in the bias to attend to
      sexual stimuli. In contrast, the comparison group of eugonadal men not
      administered T showed no mood or sexual behavior changes across the two test
      sessions. These data support a positive relationship between T and sexual
      interest, sexual arousal, and sexual enjoyment in men.

PMID- 9154432
TI  - The role of prostaglandin F2 alpha and oxytocin in the reproductive behavior of a
      marsupial, Bettongia gaimardi.
AB  - Bettongs give birth on the night that their large pouch young finally vacates the
      pouch. We have hypothesized that hormones associated with this birth are also
      involved in pouch vacation. Injections of prostaglandin F2 alpha (PGF2 alpha)
      caused contractions of the pouch. In a separate experiment PGF2 alpha caused
      pouch vacation; oxytocin had a similar effect but with a longer latency. In
      addition both hormones induced birth behavior in adult and immature females as
      well as in males. When a prostaglandin synthesis inhibitor (Finadyne) was given
      first, oxytocin failed to produce birth behavior or pouch vacation. This finding
      leads us to suggest that oxytocin exerts its behavioral effects via prostaglandin
      synthesis. These experiments are the first to demonstrate an effect by oxytocin
      on reproductive behavior in a marsupial.

PMID- 9154433
TI  - The socioendocrinology of adolescent development in male rhesus monkeys (Macaca
      mulatta).
AB  - Observations were made on four captive breeding groups of rhesus monkeys in order
      to measure hormonal, behavioral, and genital changes in adolescent males during
      the annual mating season. Three questions were addressed with regard to possible
      effects of social environment upon reproductive maturation: (1) Does male
      agonistic rank influence adolescent development? (2) Does affiliation between
      adolescent males and adult females during the mating season influence the males'
      reproductive development? (3) Does maternal rank exert any effect upon
      reproductive maturation in adolescent sons? In many (but not all) cases male rank
      was positively correlated with circulating testosterone and testes weights during
      the mating season. Affiliative behavior (allogrooming and sexual interactions)
      between adolescents and adult females in their social groups bore no relationship
      to the degree of reproductive maturation in males. Mounts involving intromission
      were infrequent, but sons of high-ranking mothers gained significantly more
      intromissions than sons of lower-ranking females. Maternal rank was also found to
      correlate with circulating testosterone levels, testes weights, growth of the
      baculum (os penis), and maintenance of body weight in adolescent sons during the
      mating season. By contrast, levels of beta-endorphin in the cerebrospinal fluid
      of adolescent males did not correlate with social rank, testosterone levels, or
      genital development. These findings point to possible effects of maternal rank,
      as well as intermale agonistic rank, in determining reproductive maturation
      during adolescence in the male rhesus monkey.

PMID- 9154434
TI  - Differential lateral septal vasopressin in wild-type rats: correlation with
      aggression.
AB  - The vasopressin (VP)-containing projections from the cells of the bed nucleus of
      the stria terminalis to the lateral septum (LS) are sexually dimorphic and
      dependent on gonadal steroids. Recently, the difference in VP distribution found
      among both sexes was also demonstrated in male mice genetically selected for
      different levels of intermale aggression. In the present study we examined
      whether this differential VP distribution in males also exists in an outbred
      strain of wild-type rats. After the animals were tested for their level of
      aggression, the VP content and the fiber density of the LS were measured using
      radioimmunoassay and immunocytochemistry, respectively. In addition, basal levels
      of plasma testosterone (T) were measured. Both biochemical data and
      immunocytochemical data revealed a negative correlation between VP and intermale
      aggression. Aggressive rats exhibited low levels of VP whereas intermediate and
      nonaggressive animals showed higher levels. Differences in adult levels of T were
      not found. The results are in accordance with the observations previously found
      in male mice, reconfirming the correlation between lateral septal VP and
      aggression.

PMID- 9154435
TI  - Hormonal and experiential correlates of maternal responsiveness during pregnancy
      and the puerperium in human mothers.
AB  - Two studies were undertaken (1) to determine whether human mothers undergo a
      change in maternal responsiveness during pregnancy before the birth of the baby,
      as shown for other mammalian species, and (2) to establish whether a relation
      exists between changes in maternal feelings and attitudes and changes in
      hormones. In both studies prospective first-time mothers completed an extensive
      set of questionnaires, covering a broad range of issues, including a set of 76-
      to 100-item likert scales concerning attitudes toward infants, childbirth,
      pregnancy, caretaking, and other interpersonal relationships. In the first cross
      sectional study, mothers completed the questionnaires at one of seven time
      points, ranging from prior to pregnancy to 3 months postpartum. In the
      longitudinal study, questionnaires were completed repeatedly throughout this same
      time period. In addition, blood was taken at these same time points and assayed
      by RIA for plasma concentrations of the steroids, estradiol, progesterone,
      testosterone, and cortisol. The primary findings are (1) feelings of nurturance
      grow during pregnancy and from pregnancy to postpartum; in the cross-sectional
      study, for most of the factors relating to infants or mothering, pregnancy and
      postpartum responses were more positive than prepregnancy responses; in the
      longitudinal study, many of these factors also showed elevations across pregnancy
      itself, as well as further elevations with the birth of the infant. (2) Pregnancy
      hormones were not related to the growth of attachment to the infant across
      pregnancy. (3) However, the pattern of change in the ratio of estradiol to
      progesterone from early to late pregnancy was related to postpartum attachment
      feelings. (4) Finally, hormonal correlates of attachment feelings may reflect
      effects both on feelings of nurturance directly and, indirectly, on mothers'
      feelings of well-being.

PMID- 9154436
TI  - Social and developmental influences on reproductive function in female Wied's
      black tufted-ear marmosets (Callithrix kuhli).
AB  - Although marmoset social groups may contain multiple adult females, reproduction
      is typically limited to one breeding female. A variety of endocrine and
      behavioral mechanisms have been identified that regulate fertility among female
      marmosets. In the present study, we assessed the mechanism(s) by which fertility
      is regulated in female black tufted-ear marmosets, Callithrix kuhli. The
      reproductive status of 10 daughters aged 2-24 months was evaluated by measuring
      concentrations of urinary pregnane-diol 3 alpha glucuronide (PdG) and luteinizing
      hormone (LH). Concentrations of the two hormones were typically low in daughters
      less than 12 months of age, and the profiles suggested anovulation (mean PdG < 2
      micrograms/mg Cr and mean LH < 6 ng/mg Cr). Concentrations of PdG rose
      dramatically in females older than 12 months. Eight subadult daughters commenced
      ovulatory function while still living with their family, and the remaining two
      failed to ovulate. The onset of ovarian function coincided with a change in the
      social environment in two females, but the remaining six females commenced
      spontaneous ovarian activity that was not associated with any social or
      environmental factor (mean age: 15.6 +/- 1.6 months). Ovulatory function was
      monitored in five daughters while housed in their natal family group, while
      removed from the natal family group and housed singly, and while paired with an
      unrelated and unfamiliar male. The ovarian cycles of these females housed in the
      natal group were characterized by significantly shorter luteal phases and reduced
      PdG concentrations, relative to when the females were housed on their own, and
      relative to adult breeding females (n = 6). Stimulatory cues from unfamiliar
      males were not necessary to trigger regular ovarian function in females. In this
      species, the regulation of fertility in daughters is a complex combination of
      behavioral and endocrine factors.

PMID- 9154437
TI  - Environmental stress as a developmental cue: corticotropin-releasing hormone is a
      proximate mediator of adaptive phenotypic plasticity in amphibian metamorphosis.
AB  - Environmentally induced phenotypic plasticity allows developing organisms to
      respond adaptively to changes in their habitat. Desert amphibians have evolved
      traits which allow successful development in unpredictable environments. Tadpoles
      of these species can accelerate metamorphosis as their pond dries, thus escaping
      mortality in the larval habitat. This developmental response can be replicated in
      the laboratory, which allows elucidation of the underlying physiological
      mechanisms. Here I demonstrate a link between a classical neurohormonal stress
      pathway (involving corticotropin-releasing hormone, CRH) and the developmental
      response to habitat desiccation. Injections of CRH-like peptides accelerated
      metamorphosis in western spadefoot toad tadpoles. Conversely, treatment with two
      CRH antagonists, the CRH receptor antagonist alpha-helical CRH(9-41) and anti-CRH
      serum, attenuated the developmental acceleration induced by habitat desiccation.
      Tadpoles subjected to habitat desiccation exhibited elevated hypothalamic CRH
      content at the time when they responded developmentally to the declining water
      level. CRH injections elevated whole-body thyroxine, triiodothyronine, and
      corticosterone content, the primary hormonal regulators of metamorphosis. In
      contrast, alpha-helical CRH(9-41) reduced thyroid activity. These results support
      a central role for CRH as a neurohormonal transducer of environmental stimuli
      into the endocrine response which modulates the rate of metamorphosis. Because in
      mammals, increased fetal/placental CRH production may initiate parturition, and
      CRH has been implicated in precipitating preterm birth arising from fetal stress,
      this neurohormonal pathway may represent a phylogenetically ancient developmental
      regulatory system that allows the organism to escape an unfavorable larval/fetal
      habitat.

PMID- 9154438
TI  - Striking the balance between the role of animal model and human data in hazard
      assessment.

PMID- 9154439
TI  - Commentary on the publication: Evaluation of the potential carcinogenicity and
      genetic toxicity to humans of the herbicide acetochlor.

PMID- 9154440
TI  - Human and experimental toxicology.

PMID- 9154441
TI  - Commentary: the use of maximum tolerated dose in rodent carcinogenicity bioassays
      and its relevance to human risk assessment.

PMID- 9154442
TI  - Effect of perinatal vitamin A or retinoic acid treatment (hormonal imprinting) on
      the sexual behavior of adult rats.
AB  - Single neonatal treatment with vitamin A (retinol) dramatically reduced the
      sexual activity of adult male rats. In females there was a significant decrease
      in the Meyerson index and a non significant decrease in the lordosis quotient.
      The effect of three perinatal treatments (at the first, third and fifth day) with
      all-trans retinoic acid was much weaker, causing only a significant increase in
      the time of the first ejaculation in males and non-significant decrease in the
      lordosis quotient of females. The experiments call attention to the false
      imprinting provoking effect of materials acting on members of the steroid
      receptor superfamily with possible human health aspect.

PMID- 9154444
TI  - Epidemiology of poisoning in the New Territories south of Hong Kong.
AB  - Little is known about the incidence and pattern of poisonings in Hong Kong.
      Hence, adults (subjects aged > or = 15 years) and children (subjects aged < or =
      14 years) hospitalized in the Princess Margaret Hospital in 1994 with ICD codes
      of 960-977 (medicinal poisonings) or 980-989 (non-medicinal poisonings) were
      studied. This is the main general hospital with a 24-hour emergency department
      for the 0.68 million people living in the New Territories South. Sex and age
      specific rates per 100,000 population were calculated. The incidence of poisoning
      in 1994 was 113.5/100,000. The incidence was higher in males than in females
      (130.0 vs 96.4/100,000). Poisoning was more common in adults than in children
      (128.8 vs 44.9/100,000). Subjects with medicinal poisonings were predominantly
      young females and hypnotics/sedatives were the main agents involved. In contrast,
      males aged 35-64 years predominated in non-medicinal poisonings, which were
      mostly related to alcohol. In children, medicinal poisonings were more common
      than non-medicinal poisonings (24.9 vs 20.2/100,000). All of the nine deaths were
      adults.

PMID- 9154443
TI  - Induction of cytochrome P450 3A by retinoids in rat hepatocyte culture.
AB  - 1. Rat hepatocytes cultured on a Matrigel matrix were exposed for 48 h to all
      trans-retinoic acid, 9-cis-retinoic acid, 13-cis-retinoic acid or fenretinide. 2.
      Cytochrome P450 3A (CYP3A) RNA levels were increased by approximately eightfold
      in hepatocytes treated with the retinoids compared to control cultures. 3. CYP1A1
      and CYP1A2 RNA levels were only slightly affected or unaffected by the retinoids.
      4. The induction of CYP3A by these therapeutically-useful retinoids suggests that
      they may share a common mechanism for accelerated drug catabolism and acquired
      clinical resistance.

PMID- 9154445
TI  - No linkage of the cytochrome P-450IIE1 (CYP2E1) C1/C2 polymorphism to
      schizophrenia.
AB  - We investigated, using PCR-SSCP analysis, the relationship between schizophrenia
      and the polymorphism of d-benzphetamine N-demethylase (cytochrome P-450j or
      CYP2E1), which metabolizes psychotropic substances such as d-benzphetamine and
      alcohols. Among 41 patients with schizophrenia, no statistically significant
      change in the frequency of the mutant (C2) allele relative to in controls was
      found, and no novel structural mutation in the CYP2E1 gene, which would be
      expected to alter the CYP2E1 protein, was found. This could be explained by no
      linkage of the CYP2E1 gene (mutations in the exon 1-9, and C1/C2 polymorphism) to
      schizophrenia.

PMID- 9154446
TI  - Oral N-acetylcysteine protects against perfluoroisobutene toxicity in rats.
AB  - 1. Perfluoroisobutene, a pyrolysis product of polyetrafluoroethene may cause
      pulmonary oedema and death when inhaled. Oral N-acetylcysteine has shown
      protection against inhalation of perfluoroisobutene and in this study we have
      tried to elucidate the mechanism by which protection is mediated. 2. Protection
      against the lethal effects of inhaled perfluoroisobutene has been shown when N
      acetylcysteine has been orally administered 4, 6 or 8 h before gas exposure. 3.
      Plasma levels of cysteine, glutathione and N-acetylcysteine were increased for up
      to 7 h following oral administration of Nac. 4. N-acetylcysteine was not detected
      in the bronchioalveolar lavage fluid following oral administration. 5. Duration
      of protection in vivo has been related to the duration of increased thiol levels
      in the plasma.

PMID- 9154447
TI  - Leaded gasoline abuse: the role of tetraethyl lead.
AB  - Volatile substance abuse is practised worldwide however reports of the abuse of
      leaded gasoline have been limited to northern Canada, southwestern USA and the
      Australian Outback. Chronic, heavy abuse of leaded gasoline results in an
      encephalopathy, cerebellar and corticospinal symptoms and signs, dementia, mental
      status alterations, and persistent organic psychosis. Much of this is due to the
      hydrocarbons of gasoline while the tetraethyl lead contributes to the altered
      mental status and is responsible for the persistent psychosis. Lead chelation
      therapy is not rational and has not been shown to benefit these patients.

PMID- 9154448
TI  - The efficacy of calcium gluconate in ocular hydrofluoric acid burns.
AB  - 1. Although calcium gluconate (CG) is recommended in the treatment of
      hydrofluoric acid (HF) eye burn its efficacy seems to be controversial, and
      controlled human or animal studies are limited. The study's objective is to
      compare the efficacy of 1% CG and normal saline irrigation for the treatment of
      HF eye injury in animals. 2. 0.05 ml 2% HF was instilled to anesthetized rabbit's
      eyes. One minute later, four treatment groups were studies: (1) irrigation with
      normal saline followed by topical antibiotics, corticosteroids and cycloplegics
      for 48 h (n = 10); (2) irrigation with 1% CG followed by the same topical
      treatment (n = 9); (3) as group 1 and 1% CG drops over 48 h (n = 10); (4) as
      group 3, and injection of 1% CG subconjunctivally after irrigation (n = 9). 3.
      Corneal erosion area, corneal haziness, conjunctival status, vascularization
      (pannus) and acidity were assessed before injury, immediately after initial
      treatment and 1, 2, 7 and 14 days thereafter by slit lamp aided by fluorescein
      staining. 4. Conjunctival pH dropped from 6.0-6.5 to 2.5-3 after injury and
      increased to 6-6.5 after irrigation. Corneal erosion: smaller in groups 2, 3,
      significantly so at 2 days, but not different at 14 days. Corneal haziness: more
      severe in group 4, at 14 days, insignificant. Conjunctival damage: significantly
      worse in group 4 at 2, 7 and 14 days. Pannus appeared in 2-4 eyes in each group.
      5. It seems that for HF injury 1% CG did not have any significant advantage over
      saline irrigation and topical treatment only. It might have some initial and
      temporary effect on healing process especially that involving erosion. Given
      subconjunctivally, 1% CG may be toxic and worsens clinical outcome.

PMID- 9154449
TI  - Granulocyte-colony stimulating factor in the treatment of colchicine poisoning.
AB  - 1. Colchicine is a highly active alkaloid used in the treatment of gouty
      arthritis and pseudogout. In overdose colchicine inhibits cell division effecting
      organs with a high rate of cell turn-over, such as the gastrointestinal tract and
      bone marrow. Early fatality results from cardiovascular collapse and respiratory
      failure, however pancytopenia and overwhelming septicaemia can occur later. 2. We
      describe a case of suicidal ingestion of 25-30 mg of colchicine in a previously
      healthy 43-year-old woman. Initial symptoms were mainly gastrointestinal. By day
      5 she had developed severe pancytopenia and early sepsis, which were successfully
      treated using granulocyte colony stimulating factor (G-CSF) 600 micrograms s.c.
      3. In vitro G-CSF is produced by the haematopoietic system. However, G-CSF can
      now be produced by recombinant DNA cloning technology and thus is available
      clinically. 4. There is no recognised antidote for colchicine poisoning and
      treatment is symptomatic. Fab fragments may have a promising future in
      eliminating colchicine from the body, but are currently not clinically available.
      In those patients that survive the initial phase of poisoning, G-CSF offers an
      effective method of treating the pancytopenia and preventing overwhelming
      septicaemia. Daily monitoring of the patient's haematological status is strongly
      recommended.

PMID- 9154450
TI  - Report of Multiple Chemical Sensitivities (MCS) Workshop, Berlin, Germany, 21-23
      February 1996. PCS/96.29 IPCS, Geneva, Switzerland.

PMID- 9154451
TI  - The Fas-based mechanism of lymphocytotoxicity.

PMID- 9154452
TI  - Minor histocompatibility antigens: from T cell recognition to peptide
      identification.

PMID- 9154453
TI  - Thymocytes positively select thymocytes in human system.
AB  - We previously demonstrated the expression of MHC class II molecules in a
      significant percentage of human fetal and postnatal thymocytes. These results, at
      that time, raised the question as to whether the MHC class II molecules on
      immature thymocytes could actively be involved in the selection of immature T
      cells. We have developed a human reaggregate culture system to address this
      issue. Surprisingly, despite the fact that thymic epithelial cells (TECs) have
      been shown to be a major selecting cell type of positive selection, we were
      clearly able to see the involvement of MHC class II+ thymocytes during selection
      process through T-T interaction. In addition, maturation to single positive (SP)
      cells occurred only in the presence of MHC class II molecules and immature
      thymocytes were found to be arrested at the double positive (DP) stage of
      differentiation by blocking of TCR recognition of MHC class II molecules. All
      these results strongly suggest that human MHC class II+ thymocytes actively
      participate in the selection of the TCR repertoire, for which TCR recognition of
      peptide/MHC class II may be an initial determining step.

PMID- 9154454
TI  - Allele-specific variation in the degeneracy of major histocompatibility complex
      (MHC) restriction.
AB  - The role of peptides in determining immune responses for both allorecognition and
      antigen-specific recognition has been clearly documented. The importance of
      different regions of the major histocompatibility complex (MHC) class II molecule
      in contributing to recognition has been demonstrated by studies involving site
      directed mutagenesis and exon shuffling. These studies have indicated that the N
      terminal region of the MHC class II molecule has a role to play in contributing
      to the T-cell receptor (TCR)-MHC-peptide interaction. Variation in the importance
      of different regions of the MHC class II molecule may be dependent on different
      aspects of this interaction, such as restriction specificity and affinity of the
      responding T-cell clone, and the nature of the bound peptide. We demonstrate here
      that the degree of T-cell degeneracy may be allele dependent. Thus, a series of
      exon-shuffled molecules were generated by shuffling the first and second variable
      region of a particular DR beta 1 molecule with the third variable region of a
      different DR beta 1 molecule. A panel of transfectants, which expressed these
      hybrid molecules, was then generated and used as antigen-presenting cells (APCs).
      A panel of peptide-specific T-cell clones was generated using the native HLA-DR
      molecules as the restricting elements. For the majority of restricting alleles,
      HLA-DRB5*0101, HLA-DRB1*1101, and HLA-DRB1*0701, all three variable regions were
      required for recognition. The exception to this observation was HLA-DRB1*0401,
      which was degenerate. Such degeneracy may facilitate the breakdown of self
      tolerance through the cross-reactive recognition of other alleles in DR4/DR"x"
      heterozygotes. Such an observation as this may contribute to our understanding of
      the etiopathology of rheumatoid arthritis, an autoimmune disease strongly
      associated with HLA-DRB1*0401.

PMID- 9154455
TI  - A single residue polymorphism at DR beta 37 affects recognition of peptides by T
      cells.
AB  - Single amino acid polymorphism at residue 37 of the HLA-DR beta chain (DR beta
      37) between DRB1*0406 and 0403 markedly influences susceptibility to the insulin
      autoimmune syndrome. We investigated the effects of DR beta 37 polymorphism
      regarding recognition of nonself peptides by a T-cell clone, YN5-32, specific to
      a streptococcal peptide (M12p54-68) presented by the DRB1*0406 molecule. YN5-32
      responded better to M12p54-68 presented by allogeneic DRB1*0403 with a single Tyr
      substitution at DR beta 37-Ser of the DRB1*0406 molecule. One hundred and fifty
      four peptides carrying single residue substitutions at each of the core residues
      57-65 of M12p54-68, were tested for full agonistic and TCR antagonistic
      activities. Forty-six peptides showed full agonism, 34 analogues exhibited TCR
      antagonism, and 45 analogues exhibited neither full agonism nor TCR antagonism,
      irrespective of the presenting molecules (DRB1*0406 or 0403). On the other hand,
      29 analogue peptides substituted at each of residues 57-63 of M12p54-68 were
      recognized differently by YN5-32, depending on the presenting molecules. These
      observations indicate that 1) single amino acid polymorphism (Ser-Tyr) at the DR
      beta 37 residue induced a conformational change distinguished by TCR in some but
      not all peptides; and 2) these conformational changes were observed even in
      analogue peptides carrying single residue substitutions at residues far from a
      putative DR beta 37 contact site. These findings provide further evidence for
      altered human T-cell responses induced by TCR ligands with minor modifications.

PMID- 9154456
TI  - Effect of polymorphism of the HLA-DPA1 chain on presentation of antigenic
      peptides.
AB  - Human T-cell clones that recognize a peptide from mycobacterial heat shock
      protein 60 in the context of HLA-DP were found to be sensitive to changes in the
      DPA1 chain of the restricting element, optimal responses being seen with the
      combination HLA-DPA1*0201 and HLA-DPB*0301. HLA-DP dimers containing HLA-DPA1*01
      were only able to present antigenic peptides to T-cell clones when peptides were
      present throughout the period of coculture of T cells with antigen presenting
      cells. In contrast the optimal HLA-DP dimer could also stimulate T-cell clones
      maximally when incubated with peptides for 1 h and then thoroughly washed. This
      suggests that the DPA1 polymorphism influenced the strength of binding of
      antigenic peptides to the HLA-DP dimer. Modeling studies identified amino acid 31
      of DPA1 as the polymorphic residue most likely to account for this effect. This
      is the first demonstration that the relatively limited polymorphism displayed by
      DPA1 has functional consequences.

PMID- 9154457
TI  - Self-peptide ligands affect T cell recognition of the homologous influenza A
      matrix virus peptide M.58-66: modification of the HLA-A2.1/peptide complex
      structure and T cell antagonism.
AB  - The cytotoxic T lymphocyte (CTL) response directed against the immunodominant
      peptide M.58-66 from the matrix of influenza A virus presented by the HLA-A2.1
      molecule is characterized by a restricted T cell repertoire. This limitation may
      be due to selective pressure induced by endogenous homologous ligands responsible
      for both positive and negative selection in the thymus and partial activation in
      peripheral T cell responses. We have used three self-protein-derived peptides
      homologous to M.58-66 to study their HLA-A2.1 binding capacity and recognition by
      M.58-66-specific HLA-A2.1-restricted CTLs. We show that they antagonize M.58-66
      reactive T cells, presumably by the formation of altered HLA-A2.1 complex
      conformations. The results are discussed with reference to the role of endogenous
      ligands homologous to antigenic peptides in T cell repertoire selection,
      tolerance, and overall regulation of the immune response.

PMID- 9154458
TI  - Soluble HLA class I and class II molecule levels in serum and cerebrospinal fluid
      of multiple sclerosis patients.
AB  - Increased concentrations of soluble HLA class I and class II molecules (sHLA-I
      and sHLA-II) have been observed in infectious, inflammatory, and autoimmune
      diseases. Because autoimmune mechanisms are considered to play a role in the
      pathogenesis of multiple sclerosis (MS), we decided to dose sHLA-I and sHLA-II in
      serum and cerebrospinal fluid (CSF) of MS patients comparing their concentrations
      with those observed in serum and CSF of patients with other neurologic diseases
      (OND) without evidence of neuroradiologic involvement of central nervous system
      (CNS) and in serum of healthy donors. The serum concentrations of sHLA-I were
      higher in both MS and OND patients than in healthy donors (P < 0.05) whereas sHLA
      II serum concentrations were lower in MS patients than in both OND patients and
      healthy donors (P < 0.01). Detectable amounts of sHLA-II were observed in the CSF
      of 45% of MS patients and in CSF of only 6% of OND patients (P < 0.001). In MS
      patients a significant correlation between sHLA-I serum and CSF concentrations
      was observed (P < 0.01), whereas sHLA-II serum and CSF levels did not correlate.
      In conclusion, alterations of sHLA-I and sHLA-II serum and CSF concentrations are
      present in MS patients and could be involved in the induction of enhanced
      susceptibility to develop MS or in MS pathogenesis.

PMID- 9154459
TI  - Soluble histocompatibility class I antigens and beta 2-microglobulin in pregnant
      females and cord blood samples.
AB  - Pregnancy can be considered a successful transplantation of allogeneic paternal
      tissue to the mother. Soluble HLA class I serum levels have been found to
      increase during solid organ rejection episodes and during graft-versus-host
      disease after bone marrow transplantation. We wished to determine whether
      significant changes in sHLA class I and beta 2-microglobulin light chain levels
      occurred during pregnancy, because these may reflect adaptive changes permitting
      the acceptance of the fetal graft. Serum samples were obtained from women at
      different stages of pregnancy and in the postpartum period. Cord blood samples
      and serum samples from nonpregnant female and male controls living in the same
      geographic area in Southern Chile were also studied. The levels of sHLA class I
      heterodimers were determined by an ELISA sandwich technique; beta 2-microglobulin
      levels were measured by MEIA IMX-Abbott. There was a significant elevation of
      sHLA class I levels in the first 2 trimesters of pregnancy, followed by a
      significant drop below normal levels at the end of pregnancy, with normalization
      in the post-partum period. beta 2-microglobulin levels did not change
      significantly during pregnancy and did not correlate with sHLA class I levels. In
      cord blood samples, sHLA class I levels were lower and beta 2-microglobulin
      levels higher than those of adult controls and of mothers at the time of
      delivery. The variations in sHLA class I levels during pregnancy may reflect or
      contribute to immunoregulatory events related to the acceptance of the fetal
      graft.

PMID- 9154460
TI  - Description of a new HLA-E (E*01031) allele and its frequency in the Spanish
      population.
AB  - An HLA-E polymorphism study by oligotyping and DNA sequencing was carried out in
      the Spanish population. As a result, a new HLA-E allele (E*01031) initially
      assigned by polymerase chain reaction oligotyping as E*0104 was found. This
      allele presents a synonymous change at codon 77 (AAT-->AAC; Asn) when compared
      with the E*01032 allele. This position is located in the alpha-helix (alpha 1
      domain) and is involved in the peptide binding region of the hypothetical HLA-E
      molecule. Among 60 Spanish individuals, HLA-E*0101 presents the highest phenotype
      frequency, followed in decreasing order by E*01032, E*01031 (new allele), and
      E*0102. Also, new partial intron 1 and complete intron 2 sequences from E*0101,
      E*01031, and E*01032 are described; the sequences are identical among the three
      forms. However, the intron 2 sequence of the E*0102 allele bears a two-base
      deletion not found in apes.

PMID- 9154461
TI  - Polymorphism of the HLA-DRB1 locus in Colombian, Ecuadorian, and Chilean
      Amerinds.
AB  - We have characterized the DRB1 genotypes in a sample of 64 South American Indians
      drawn from populations in Chile, Colombia, and Ecuador. No novel DRB1 alleles
      were found in the total of 17 different alleles characterized, indicating that
      rapid allelic generation does not occur at the DRB1 loci, in contrast to HLA-B.
      Comparison between Chilean and Colombian/Ecuadorian samples revealed no major
      differences in their allelic frequencies. In the combined Amerind sample the HLA
      DRB1*0407 and HLA-DRB1*1402 alleles occurred in the highest frequencies (38% and
      22%, respectively). Genetic distance measurement showed the HLA-DRB1 frequencies
      reported here to agree with findings in other Amerind groups. The high
      frequencies of both HLA-DRB1*0407 and HLA-DRB1*1602 alleles, in conjunction with
      their absence in Siberian samples, suggest that migratory groups other than
      Siberians may have been involved in the peopling of the Americas.

PMID- 9154462
TI  - Quality control for DNA contamination in laboratories using PCR-based class II
      HLA typing methods.
AB  - Quality control (QC) in laboratories performing molecular histocompatibility
      class II typing often includes a polymerase chain reaction (PCR) approach for
      monitoring DNA contamination. An oligonucleotide primer set was designed,
      (RBQBf/RBQBr), which is specific for nonpolymorphic regions of the DR-B, DQ-B,
      and DP-B consensus sequences with an expected PCR product size of 81 bp.
      RBQBf/RBQBr detected genomic DNA from reference cell lines LWAGS and BM21 (50 to
      100 picograms) as well as DR-B, DP-B, and DQ-B amplicon (1 copy). Additionally,
      RBQBf/RBQBr detected SSP products from routine DR-B and DQ-B typings. Validation
      studies employing controlled DNA contamination of laboratory surfaces revealed
      that increasing amounts of wipe test samples (5% to 20% v/v) were inhibitory to
      the wipe test PCR, whereas lower amounts (1% to 2%), or alternatively, a diluted
      wipe test sample, increased the sensitivity of the test and optimized the
      results. Collectively, this study describes a primer set, RBQBf/RBQBr, which
      detects both genomic DNA and DR-B, DQ-B, or DP-B amplicon and furthermore
      illustrates the necessity of routine testing for potential inhibitory factors
      that may be introduced into the wipe test PCR.

PMID- 9154463
TI  - Nomenclature for factors of the HLA system, update March 1997.

PMID- 9154464
TI  - Viral vectors for gene therapy of hematopoietic cells.
AB  - Hematopoietic cells, in particular hematopoietic stem cells, are important
      targets for the development of gene therapy for hematological and other
      disorders. So far, simple retroviral vectors based on Murine Leukemia Virus (MLV)
      have been the main delivery vehicles for the transfer of corrective genes into
      primary hematopoietic cells. While the gene transfer efficiency of progenitor
      cells has been very efficient using these vectors, it has been much more
      problematic to obtain efficient gene transfer into repopulating human
      hematopoietic stem cells. The main reason for this is due to the quiescent nature
      of these cells and the fact that MLV-based vectors require dividing target cells.
      It may be that efficient gene transfer into hematopoietic stem cells can be
      accomplished by stimulating the cells to divide in vitro or by developing new
      vector systems that can isolate transduced cells or that can deliver genes
      permanently into nondividing target cells. This review will discuss the progress
      and problems of these approaches in developing effective gene therapy for
      hematopoietic cells.

PMID- 9154465
TI  - An optimized method for cell-based phage display panning.
AB  - BACKGROUND: Traditional methods of phage display panning, bind purified antigen
      to plates or other solid phases to which libraries are then applied, followed by
      vigorous washings in detergent-supplemented buffers to select for specific phage
      Fab. These methods are not directly applicable to antigens in their native
      environment on cell surfaces or in settings where the target antigen is unknown.
      OBJECTIVES: To develop a model antigen system employing whole cells rather than
      purified protein immobilized on a substrate; to optimize methods for phage
      display panning using a cell-based system. RESULTS: Specificity of binding of
      phage Fab to antigen on cells was demonstrated by output titer and by flow
      cytometry. Output titers showed a plateau and binding advantage, after four
      washes, corresponding to removal of most non-specifically bound phage. Enrichment
      advantage was independent of input phage number. Longer incubation times, to cell
      tolerance, improved specific binding. Temperature had modes impact as a variable
      in the panning and washing. An increase in output titers paralleled enrichment
      for specific phage Fab. CONCLUSION: An optimized method applied to whole cells
      can productively enrich specific phage Fab in mixtures with large excesses of non
      specific phage Fab over several rounds of panning.

PMID- 9154466
TI  - Cloning and expression of human V-genes derived from phage display libraries as
      fully assembled human anti-TNF alpha monoclonal antibodies.
AB  - BACKGROUND: With the advent of phage antibody libraries, access to completely
      human antibody fragments is feasible, either by direct selection from human
      antibody libraries, or by guided selection. After selection, Fabs and scFvs may
      need to be expressed as complete antibodies in mammalian cells for further
      characterisation, or if effector functions are required. OBJECTIVES: To rebuild
      and express the human anti-TNF alpha antibody Fab-P3A2 (isolated as a Fab
      fragment from phage display libraries by guided selection) as a fully assembled,
      functional human antibody (gamma-1, lambda) in Sp2/0 myeloma cells, and to
      perform preliminary characterisation studies of the secreted IgG1 molecule. A
      further objective was to investigate the kinetics of human antibody production
      and the stability of antibody secretion in transfectomas cultured in various
      media formulations. STUDY DESIGN: A tripartite strategy was employed for cloning
      heavy chain gene (VH)-P3 and light chain gene V lambda-A2-C lambda into mammalian
      cell expression vectors p alpha Lys-30 and p alpha Lys-17 respectively. The cell
      line P3A2.B5 was isolated after co-transfection of Sp2/0 mouse myelomas with the
      constructs, expanded and weaned into a protein free medium. Fully assembled Ig
      P3A2 antibody was purified by Protein A affinity chromatography and characterised
      with respect to size of antibody chains, and affinity for human TNF alpha.
      Stability of secretion was investigated by extended serial sub-culture and
      analysis of P3A2.B5 sub-clones. Strategies of media enrichment were tested for
      any effect on antibody productivity by selected P3A2.B5 sub-clones. RESULTS: The
      cell line P3A2.B5 secreted an assembled, human antibody Ig-P3A2, with heavy and
      light chains of molecular weight 55 and 28 KD respectively. Equilibrium capture
      studies showed Ig-P3A2 to have a dissociation constant of approximately 1.5 x 10(
      8) M. The mean specific productivity of the cell line increased from 1.2
      pg/cell/day to 7.8 pg/cell/day by a combination of medium enrichment and serum
      reduction. Prolonged serial sub-culture of P3A2.B5 showed the cell line to be
      unstable with respect to antibody secretion. CONCLUSIONS: We have outlined a
      method for expression of human V genes as assembled antibodies in Sp2/0 myeloma
      cells. A cloning strategy for the stable expression of scFv or Fab genes isolated
      from phage display libraries as assembled human antibodies of the IgGl subclass
      in Sp2/0 myeloma cells has been described. For maximising specific productivity
      of antibody-producing cell lines, supplementation of culture media with glucose,
      glutamine and amino acids increases antibody yield significantly compared to that
      in conventional media, indicating the latter is stoichiometrically limiting for
      production purposes.

PMID- 9154467
TI  - Humanization of an antibody recognizing a breast cancer specific epitope by CDR
      grafting.
AB  - BACKGROUND: Muc1-H23 is a cell surface mucin that is expressed on normal breast
      luminal epithelial cells and over-expressed in most breast tumors. In addition,
      Muc-1 expressed by malignant cells is glycosylated differently than Muc-1
      expressed by normal cells. This difference in glycosylation exposes a peptide
      epitope on malignant cells which is not exposed on normal cells. Murine
      monoclonal antibody H23 recognizes this epitope and stains 91% of breast cancers,
      but only 1/56 non-malignant breast tissue samples. OBJECTIVE: To create a human
      antibody that was equivalent to H23 for potential uses in imaging and/or the
      therapy of breast cancer. STUDY DESIGN: We decided to humanize H23 by CDR
      grafting using overlap PCR, and to this end, designed and constructed a bacterial
      expression vector that would allow V-regions, cloned via unique restriction
      sites, to be expressed as Fab fragments. In this way, we hoped to be able to
      rapidly evaluate Fab constructs for binding to Muc-1 and to cells and tissue
      sections that expressed the antigen. RESULTS: A fully humanized Fab fragment was
      able to bind Muc-1 peptide, as well as breast cancer cells known to express the
      epitope and tissue sections, generally showing the same reactivity as the native
      antibody. In addition, an analysis of sFab expressed with a [His]6 tag preceded
      by a factor Xa proteolytic cleavage site suggested that E. coli periplasmic
      signal peptidase was able to cleave the factor Xa site, thereby removing the
      [His]6 tag. CONCLUSION: We have generated a human antibody that is capable of
      recognizing a tumor specific epitope expressed by 91% of breast cancers.

PMID- 9154468
TI  - Harlequin granulocyte-colony stimulating factor interleukin 6 molecules with
      bifunctional and antagonistic activities.
AB  - BACKGROUND: The granulocyte-colony stimulating factor (G-CSF) and the interleukin
      6 (IL-6) are part of a large family of cytokines that regulate the production and
      the functional activity of hemopoietic cells. Recent studies have shown that IL-6
      and G-CSF share structure homology and have partially overlapping functions.
      OBJECTIVES: Our research gives some information for planning the production of
      new artificial cytokines in order to establish whether we could obtain molecules
      that had two functions or an inhibitory function. STUDY DESIGN: Fourteen
      different chimeric molecules (called Harlequin molecules) of human IL-6 and G-CSF
      have been produced exchanging the sequence encoded by the 2nd to the 5th exon of
      the genes of the two cytokines. RESULTS: In order to test their biological
      activity we performed different assays: proliferation of murine B9-cells and
      immunoglobulin production from human Epstein-Barr virus (EBV)-transformed B-cell
      lines for IL-6; induction of granulocytic differentiation of the murine 32DC13(G)
      cell line and normal bone marrow progenitor cells for G-CSF. Some chimeric
      molecules maintain the activity of either IL-6 and G-CSF and at least one
      (Harlequin 11) has both biological activities. One chimeric protein has no
      biological activity but competes, presumably at the receptor level, for the
      activity of the intact cytokine. CONCLUSION: These studies can provide important
      information on the structure/function of the two cytokines. The bifunctional
      Harlequin molecule 11 could be a potential candidate as therapeutic agent.

PMID- 9154469
TI  - Humanization of a mouse monoclonal antibody that blocks the epidermal growth
      factor receptor: recovery of antagonistic activity.
AB  - BACKGROUND: Antibody humanization by transplanting the complementarity
      determining regions (CDRs) of a murine antibody to a human framework aims to
      reduce the response of the human immune system against a foreign molecule.
      Frequently, however, some murine amino acids from the framework have to be
      retained to recover binding affinity. OBJECTIVES: To redesign R3, a mouse
      monoclonal antibody (mAb) that binds the human epidermal growth factor (EGF)
      receptor and inhibits the binding of EGF, to be a human IgG1. STUDY DESIGN: The
      light and heavy chains of REI and Eu, respectively, were selected as human
      immunoglobulin (Ig) frameworks for CDR-grafting based on their high homology with
      the corresponding sequences of murine R3. Molecular modeling was used to analyze
      the possible effects of mutating murine residues that underlie the CDRs. RESULTS:
      CDR-grafting dramatically reduced the binding capability of the antibody.
      Molecular modeling suggested that two amino acids (Thr 76 and Thr 93), among five
      immunoglobulin heavy chain variable region (VH) residues underlying the CDRs,
      were critical for antigen binding. The five residues were mutated back to the
      original murine amino acids in different combinations contained in six variants
      of humanized antibodies. In agreement with molecular modeling analysis. The
      variant in which three murine residues were retained (Ser 75, Thr 76 and Thr 93)
      exhibited a similar capacity to inhibit the binding of 125I-labeled EGF to its
      receptor as compared with the original antibody. This humanized antibody was at
      least 2-fold less immunogenic in African Green monkeys than the chimeric
      antibody. CONCLUSIONS: Only very few mutations in the frameworks may be necessary
      to recover the binding capability of a humanized antibody. Molecular modeling can
      serve as a powerful tool to identify residues critical for binding.

PMID- 9154470
TI  - Ethical aspects in infection control.

PMID- 9154471
TI  - Role of environmental contamination in the transmission of vancomycin-resistant
      enterococci.

PMID- 9154472
TI  - Risk factors for surgical-wound infection in general surgery: a prospective
      study.
AB  - OBJECTIVE: To quantify surgical-infection rate, to assess adherence with the
      antibiotic prophylaxis protocol, and to identify independent factors associated
      with surgical-wound infection (SWI). METHODS: We carried out a prospective study
      of a cohort of 2,237 general surgery patients with postsurgery stays of more than
      48 hours. Odds ratios (OR) were estimated using unconditional multiple logistic
      regression. SETTING: A 1,300-bed, university-affiliated, tertiary-care hospital
      in Madrid, Spain. RESULTS: 254 patients developed SWI. The rate of adherence to
      the antibiotic prophylaxis protocol was 63.5%. Eight factors were independently
      associated with risk of SWI: age (OR = 1.2 for every 10 years of age); wound
      classification (clean-contaminated, OR = 6.4; contaminated, OR = 3.7; dirty or
      infected, OR = 9.3); antimicrobial prophylaxis (OR = 0.5); stay prior to surgery
      (OR = 1.1 for every 3 days); duration of operation (OR = 1.5 for every 60
      minutes); malignant neoplasm (OR = 1.7); emergency procedure (OR = 1.99);
      intensive-care unit stay prior to surgery (OR = 2.6); and antimicrobial
      prophylaxis administered 2 or more hours before operation (OR = 5.3). CONCLUSION:
      In general, antimicrobial prophylaxis protects against SWI (OR = 0.5); however,
      administration 2 hours or more before the operation increases the risk of SWI by
      a factor of 5.3. Therefore, measures should be taken to ensure the correct timing
      of antimicrobial prophylaxis.

PMID- 9154473
TI  - Risk factors associated with isolation of Stenotrophomonas (Xanthomonas)
      maltophilia in clinical specimens.
AB  - OBJECTIVE: To determine risk factors for patients whose cultures grew
      Stenotrophomonas maltophilia. DESIGN: Retrospective case-control study of 60
      patients with cultures positive for S maltophilia, matched by specimen site to
      120 controls whose cultures grew other gram-negative aerobic bacteria. SETTING:
      University medical center. RESULTS: S maltophilia was identified from the
      following sites: respiratory (36), wound (13), urinary (6), blood (4), and
      cerebral spinal fluid (1). By univariate analysis, cases had a higher risk of
      exposure than controls for ampicillin (P < .001), gentamicin (P < .001),
      vancomycin (P = .001), metronidazole (P = .003), piperacillin (P = .007),
      cefotaxime (P = .014), ceftazidime (P = .017), ciprofloxacin (P = .030),
      tobramycin (P = .040), and chronic respiratory disease (P = .024). Length of time
      foreign objects were in place prior to positive culture differed significantly
      between cases and controls only for endotracheal tubes in patients with
      respiratory isolates (median number of days: 12.5 for cases, 5 for controls; P =
      .007). For patients with urinary tract infections, having a urinary catheter
      increased the odds of infection 10 times over controls. Exposures found by
      multivariate analysis to be significantly more prevalent in cases than controls
      included ampicillin, cefotaxime, erythromycin, gentamicin, metronidazole,
      piperacillin, tobramycin, chronic respiratory disease, and female gender. Odds
      ratios were > 1 indicating higher risk for cases, except for erythromycin, which
      had an odds ratio < 1. CONCLUSIONS: The primary risk factor associated with
      isolation of S maltophilia was antibiotic use. For patients with pulmonary
      infections, chronic respiratory disease and length of time an endotracheal tube
      was in place also contributed to the risk. This suggests that judicious use of
      antibiotics may prevent some cases of S maltophilia infection.

PMID- 9154474
TI  - Nosocomial transmission of Trichophyton tonsurans tinea corporis in a
      rehabilitation hospital.
AB  - OBJECTIVE: Investigate the nosocomial transmission of Trichophyton tonsurans
      tinea corporis. DESIGN: Descriptive study of a nosocomial epidemic of tinea
      corporis. SETTING: A free-standing inpatient rehabilitation facility.
      PARTICIPANTS: Patients and healthcare workers present on an inpatient
      rehabilitation ward at the time of transmission of tinea corporis. RESULTS: T
      tonsurans tinea corporis was transmitted from one patient to four healthcare
      workers despite early diagnosis and treatment. Infection rates for healthcare
      workers having major, moderate, and minor contact with the index case were 30%,
      17%, and 0%, respectively (overall rate, 25%). CONCLUSIONS: This study identifies
      rehabilitation inpatients as another population in which nosocomial transmission
      of T tonsurans tinea corporis can occur. The high attack rate and transmission,
      despite early diagnosis and treatment, emphasizes the need for isolation
      precautions.

PMID- 9154475
TI  - Impact of changes in catheter management on infectious complications among
      children with central venous catheters.
AB  - OBJECTIVES: To characterize and enumerate central venous catheter (CVC)-related
      complications among children with chronic illnesses, and to reduce the
      complication rate through changes in CVC management and education. DESIGN: A
      prospective observational study followed by an educational program and a
      nonrandomized interventional trial. SETTING: The Children's Hospital of
      Philadelphia, a tertiary, pediatric facility. PATIENTS: 268 children with
      Broviac, Hickman, or Infusaport catheters in place during 58,290 catheter days.
      INTERVENTIONS: Development and implementation of protocols for cleaning insertion
      site and hub, use of nonocclusive dressings, and manipulation of access; formal
      staff and parental education about protocols. RESULTS: CVC-related infections
      fell from 4.58/1,000 catheter-days preintervention to 3.83 postintervention (risk
      ratio [RR], 0.20; 95% confidence interval [CI95], 0.89-1.622; P = .25); exit-site
      infections fell from 0.58 to 0.11 (CI95, 1.22-45.64; P = .02); rates among
      infants on the surgical service fell from 15.46 to 6.67 (RR, 2.31; CI95, 1.10
      4.30; P = .02). CONCLUSIONS: Education and changes in management protocols
      reduced the incidence of exit-site infections among all patients and reduced the
      overall infectious complication rate among the infants receiving parenteral
      nutrition on the surgical service. Other interventions are needed to decrease
      further the infectious complications in these children.

PMID- 9154477
TI  - Parvovirus B19-antibody serosurvey in 500 developmentally disabled subjects.
AB  - Sera of 500 residents were screened for parvovirus B19 immunoglobulin M (IgM) and
      immunoglobulin G (IgG) by enzyme-linked immunosorbent assay. Positive IgM and
      equivocal IgG or IgM results were confirmed by immunofluorescent antibody and
      Western blot. IgM was detected in 13 sera (2.6%), and IgG was detected in 285
      (57%). Records of IgM-positive residents contained no evidence of erythema
      infectiosum or polyarthropathy.

PMID- 9154476
TI  - Colonization with vancomycin-resistant Enterococcus faecium: comparison of a long
      term-care unit with an acute-care hospital.
AB  - OBJECTIVE: To compare the epidemiology of vancomycin-resistant Enterococcus
      faecium (VRE) in a long-term-care unit and an acute-care hospital. DESIGN: Point
      prevalence surveys for VRE rectal colonization of patients were carried out over
      a 21-month period in patients in a long-term-care unit and an acute-care hospital
      (medical ward and intensive-care units). The environment and hands of healthcare
      workers also were sampled for VRE. Contour-clamped homogeneous electric field
      (CHEF) electrophoresis was used to evaluate possible transmission among roommates
      and the relatedness of patient strains to those in the environment and on the
      hands of healthcare workers. SETTING: A 200-bed Veterans Affairs Medical Center
      with an attached 90-bed long-term-care unit. RESULTS: From December 1994 to
      January 1996, rectal VRE colonization of patients in the long-term-care unit
      increased significantly from 9% to 22%. In contrast, patients on the medical ward
      rarely were colonized after the first survey in December 1994, and only two
      intensive-care-unit patients were found to be colonized during the four surveys.
      The environment was contaminated persistently in the long-term-care unit. In the
      four surveys, carriage of VRE on hands of healthcare workers varied from 13% to
      41%; 65% of healthcare workers with VRE found on their hands worked in the long
      term-care unit. Seven different strains were identified by CHEF typing. Although
      the initial survey found only vanA strains, subsequent surveys showed vanB
      strains also were present. CONCLUSIONS: Residents of a long-term-care unit
      frequently were colonized with VRE, but infections were uncommon in this
      population. The environment of the long-term-care unit was contaminated with VRE,
      and VRE was found frequently on the hands of healthcare workers in this unit.
      Both vanA and vanB genotypes were found in this setting.

PMID- 9154478
TI  - Vancomycin-resistant enterococci in stool specimens submitted for Clostridium
      difficile cytotoxin assay.
AB  - The prevalence of, and clinical risk factors associated with, vancomycin
      resistant enterococcal colonization were investigated in patients suspected of
      having Clostridium difficile infection. Stools submitted for C difficile
      cytotoxin testing were screened for vancomycin-resistant enterococci (VRE).
      Isolates were speciated and characterized further by antibiotic susceptibility
      testing, DNA fingerprinting, and DNA:DNA hybridization for detection of specific
      vancomycin resistance genes. Of the 79 evaluable patients identified during a 3
      month period, 16.5% were VRE-positive. The VRE isolates were genetically
      heterogeneous, although all carried the vanA gene. DNA fingerprinting data
      suggest that patient-to-patient transmission occurred, implicating colonized
      patients as potential reservoirs for VRE transmission. A positive C difficile
      cytotoxin assay and diabetes mellitus were the only identifiable risk factors
      associated with VRE colonization. Patients at risk for C difficile infection
      therefore may serve as reservoirs for VRE.

PMID- 9154479
TI  - Activity of disinfectants against vancomycin-resistant Enterococcus faecium.
AB  - Vancomycin-resistant enterococci (VRE) often contaminate the hospital
      environment. We examined the activity of commonly used disinfectants against
      eight strains of VRE, using a quantitative suspension test method. Isopropyl
      alcohol and sodium hypochlorite were highly effective. Hydrogen peroxide was
      ineffective for all strains. After 10 minutes of incubation (the manufactures'
      recommended time of exposure), three phenolic and three quaternary ammonium
      compounds also were highly effective. After 3 minutes of exposure, however,
      occasional failures did occur. With the exception of 3% hydrogen peroxide, most
      disinfectants appear to be active against VRE.

PMID- 9154480
TI  - Intravascular catheter colonization in critically ill children.
AB  - In a prospective study, cultures were obtained of all intravascular catheters
      removed from children in an intensive care unit. Of 366 catheters removed from
      217 children, 110 (30%) were found to be colonized, most commonly with coagulase
      negative staphylococci. Despite the high rate of colonization, there were only
      nine instances (2%) of catheter-related bacteremia.

PMID- 9154481
TI  - Management of healthcare workers infected with hepatitis B virus, hepatitis C
      virus, human immunodeficiency virus, or other bloodborne pathogens. AIDS/TB
      Committee of the Society for Healthcare Epidemiology of America.
AB  - This article provides the current recommendations of the Society for Healthcare
      Epidemiology of America (SHEA) regarding the management of healthcare workers
      infected with hepatitis B virus (HBV), hepatitis C virus (HCV), or the human
      immunodeficiency virus (HIV). For the reasons cited in the article, SHEA now
      maintains that separate virus-specific management strategies are appropriate for
      healthcare workers who are infected with these unrelated viruses. SHEA emphasizes
      the use of appropriate infection control procedures to minimize exposure of
      patients or providers to blood, emphasizes that transfers of blood from patients
      to providers and from providers to patients should be avoided, and argues that
      infected healthcare workers should not be prohibited from participating in
      patient-care activities solely on the basis of their blood-borne pathogen
      infection. SHEA recommends that hepatitis B e-antigen-positive healthcare workers
      routinely should double glove and should not perform those activities that have
      been identified epidemiologically as associated with a risk for provider-to
      patient HBV transmission despite the use of appropriate infection control
      procedures. SHEA also recommends that HCV- and HIV-infected providers use double
      gloving for procedures, but recommends that these providers not be excluded from
      any aspect of patient care unless epidemiologically incriminated in the
      transmission of these infections despite adequate precautions. SHEA argues for
      comprehensive education concerning bloodborne pathogens for all healthcare
      providers and trainees and against mandatory pathogen-specific educational
      requirements for infected providers. SHEA recommends against specific competence
      monitoring procedures directed at these healthcare workers infected with
      bloodborne pathogens, arguing for managing infected providers in the context of a
      comprehensive approach to the management of all impaired providers. SHEA
      emphasizes the importance of worker privacy and medical confidentiality. SHEA
      emphasizes the importance of offering employees who have disabilities reasonable
      accommodation for their disabilities. The article discusses exposure management
      in detail and, in general, recommends adherence to existing guidelines for
      managing exposures to these agents. Finally, SHEA recommends against routine
      mandatory testing of providers. Specific details and the rationale for these
      recommendations are included in the body of the article.

PMID- 9154482
TI  - Intramural and extramural communication.
AB  - Effective communication with hospital administrators, with medical staff, with
      the media, and with peers in healthcare epidemiology is a vital skill for
      hospital epidemiologists. This article will describe a number of practical ways
      to improve such communication based on the author's experience, on interviews
      with senior SHEA members, and on relevant articles from the literature.

PMID- 9154483
TI  - Secular trends in the epidemiology of nosocomial fungal infections at a teaching
      hospital in Taiwan, 1981 to 1993.
AB  - OBJECTIVE: To describe the incidence and patterns of nosocomial fungal infection
      in a large teaching hospital in Taiwan. DESIGN: Prospective, hospitalwide
      nosocomial surveillance data from 1981 through 1993 were analyzed to show the
      secular trend in nosocomial fungal infection rates and to identify the most
      common pathogens and sites of infection (other than skin) in this hospital.
      SETTING AND PATIENTS: The National Taiwan University Hospital is a medical school
      affiliated hospital in the city of Taipei, Taiwan, with a 1200-bed capacity
      before 1991 and 1500 beds since 1992. It provides both primary and tertiary
      medical care. RESULTS: The overall nosocomial fungal infection rate rose from 0.9
      infections per 1000 discharges in 1981 to 6.6 per 1000 discharges in 1993, with
      the highest rate at the medical intensive-care unit (26.5/1000 discharges in
      1993). This increase in infection rate was found at four major anatomic sites of
      infection, particularly including the bloodstream (0.08-2.19/1000 discharges) and
      the urinary tract (0.36-2.95/1000 discharges). Of 256 pathogens causing
      nosocomial fungemia from 1981 through 1993, Candida albicans was the most
      commonly isolated (50.8%), followed by Candida tropicalis (17.6%). Candida
      parapsilosis (11.7%), and Candida glabrata (8.2%). As compared to isolates from
      1981 through 1988, the proportion of C parapsilosis and C glabrata isolated
      between 1989 and 1993 increased more than sixfold and fourfold, respectively. The
      increasing importance of fungal infections was confirmed further by the increased
      use of amphotericin B and azoles in this hospital. CONCLUSIONS: Candida species
      and other yeasts have become a prominent cause of nosocomial infections in this
      hospital. These fungal pathogens accounted for a higher proportion of nosocomial
      bloodstream and urinary infections than any single bacterial species. Therefore,
      it is important to conduct a prospective epidemiological study and to establish
      in vitro antifungal susceptibility testing to enhance efforts to control
      nosocomial fungal infections and to minimize the risk of emergence of antifungal
      resistance.

PMID- 9154484
TI  - Electronic mail: an imperative for healthcare epidemiologists.
AB  - Electronic mail (e-mail) offers the potential for near-instantaneous transfer of
      messages and files across thousands of miles. The same message can be sent
      simultaneously to multiple recipients and forwarded without retyping. Messages
      can be sent or read at any time, eliminating "telephone tag," and, because the
      system is paperless, lost, blurred, and incomplete, facsimile transmissions can
      be minimized. Additionally, e-mail is less expensive than overnight letter
      services or long-distance faxes. All healthcare epidemiologists should enter the
      information superhighway using e-mail. This article provides basic information
      needed to understand and begin using e-mail.

PMID- 9154485
TI  - Can CQI really work in health care? For how long?

PMID- 9154486
TI  - Accreditation and ISO: international convergence on health care standards ISQua
      position paper--October 1996.

PMID- 9154487
TI  - Under use of coronary angiography: application of a clinical method.
AB  - OBJECTIVE: To estimate the extent of under use of coronary angiography and to
      determine whether women, ethnic minorities and poor and uninsured patients are
      less likely than their counterparts to receive necessary coronary angiography.
      DESIGN: Retrospective cohort study employing chart review and patient interviews.
      SETTING: Four teaching hospitals: three government owned (public) and one private
      university medical center in Los Angeles, California. PATIENTS: Three hundred and
      fifty two patients who had a positive exercise stress test between 1 January 1990
      and 30 June 1991 and met explicitly defined criteria for the necessity of
      coronary angiography established by a multidisciplinary expert panel. MAIN
      OUTCOME MEASURES: Percentage of patients who received necessary coronary
      angiography within 3 and 12 months following exercise stress testing, adjusted
      for demographic and clinical characteristics using logistic regression. RESULTS:
      Overall 43% received necessary coronary angiography within 3 months and 56%
      within 12 months of the stress test. Women were less likely than men to receive
      necessary coronary angiography. Adjusted odds ratio (AOR) 0.54, 95% confidence
      interval (CI) 0.34-0.90 for angiography within 3 months of the stress test; AOR
      0.47, 95% CI 0.29-0.77 for angiography within 12 months of the stress test.
      Public hospital patients underwent necessary coronary angiography less often than
      private hospital patients. AOR 0.40, 95% CI 0.23-0.79 for within 3 months; AOR
      0.52, 95% CI 0.30-0.91 for within 12 months. CONCLUSIONS: Under use of coronary
      angiography can be measured and occurs to a significant degree. It is important
      to develop standards of quality to address and safeguard against under use of
      necessary medical care.

PMID- 9154488
TI  - A comprehensive model of cooperation between caregivers related to quality of
      care.
AB  - BACKGROUND: The system and delivery of health care tend to suffer from
      fragmentation, resulting in discontinuous and costly care. Local cooperation
      between caregivers is essential to achieve appropriate, timely, continuous and
      efficient care. The article develops a general comprehensive patient-centered
      model of quality of care related to local cooperation between caregivers. The
      model can be used in quality improvement and research. THE PROPOSED MODEL: Within
      the framework of Donabedian's triad (structure-->process-->outcome), cooperation
      between caregivers is divided into two parts. Firstly, client related cooperation
      (multiple caregivers to one patient) is a part of the process of health care and
      relevant for important quality aspects: appropriateness, timeliness, continuity
      of care, effectiveness and efficiency. Secondly, local cooperation between
      caregivers, which is not restricted to one patient, is called non client related
      cooperation. Such non client related cooperation creates conditions for optimal
      patient care. Non client related cooperation has different degrees, dependent on
      the existence of agreements between the caregivers (such as protocols) and
      evaluation of these agreements. The highest degree of non client related
      cooperation is continuous quality improvement. To achieve a certain degree of non
      client related cooperation, conditions must be fulfilled in several fields
      (organization, information, financing and participants). APPLICATION OF THE
      MODEL: A "how to use the model in eight steps" is given and possible
      operationalizations of key concepts in the model are outlined. Finally, the use
      of the model is illustrated by two examples.

PMID- 9154489
TI  - An evaluation of the need for shared blood donor deferral registries.
AB  - OBJECTIVE: This study examined the frequency with which allogeneic, volunteer
      blood donors who had been deferred from donation at one blood collection facility
      donated, or attempted to donate, at a second blood collection facility. METHODS:
      The blood donor computer files of two local blood collection facilities were
      combined and matched donors on the donor deferral registry of each blood
      collection facility were identified. RESULTS: Of 26,300 donors in the hospital
      based blood bank file, 6732 (25.6%) were matched to the community blood center
      donor file (active donor base approximately 275,000). Matched donors on the donor
      deferral registry at each blood collection facility numbered 427 (6.3% of total
      matched donors). A total of 103 evaluable donors (1.5% of total, or 24.1% of
      deferred, matched donors) had been deferred at one blood collection facility and
      then later donated, or attempted donation, at the other blood collection
      facility. Of these 103, 51 were allogeneic donors who had been notified of their
      deferral status and should not have subsequently attempted blood donation. Thirty
      two donors on the donor deferral registry of one blood collection facility made
      donations at the second blood collection facility which entered the general blood
      inventory. CONCLUSION: Shared donor deferral registries may be valuable at the
      local or regional level to prevent deferred blood donors from donating at other
      blood collection facilities. Whether or not a national donor deferral registry
      would be efficacious remains to be proven and deserves further study.

PMID- 9154491
TI  - Autonomy and practice: the case of complementary practitioners in the UK.
AB  - OBJECTIVE: 1. To identify the level of acceptance of the principle of British
      Medical Association (BMA) participation in the formulation of practice guidelines
      for complementary medicine amongst currently active non-orthodox practitioners in
      the UK. 2. To identify the level of support for individual BMA proposals. 3. To
      identify similarities and differences of attitude to the proposals between
      practitioners of selected non-orthodox therapies. DESIGN: A postal survey of 1000
      practitioners of complementary medicine. SETTING: The UK between late 1993 and
      early 1994. STUDY PARTICIPANTS: One thousand currently practising UK
      complementary therapists from 4 groups-chiropractic, "lay" homeopathy, medical
      herbalism and reflexology. Systematic sampling (every nth practitioner) was used
      to select 250 respondents from membership lists of relevant representative
      bodies. The reponse rate was 57%. RESULTS: The principle of BMA participation in
      policy formation was accepted by the vast majority of respondents, although 87.7%
      stipulated that this should not constitute a major role. Each of the individual
      BMA proposals received majority support. Acceptance rates varied from 59.7% to
      92.9%. Statistically significant differentiation between therapies was recorded
      on certain proposals. DISCUSSION: The revised stance of the BMA is finding a
      potentially receptive audience amongst UK complementary practitioners. There is a
      large amount of common ground between the proposals and what is acceptable to
      practitioners. However, the situation is complicated by intra-sectoral
      differentiation. Particular therapy and issue-specific barriers exist to the
      universal utilization of the kind of measures proposed.

PMID- 9154490
TI  - Patients' satisfaction with surgical care impaired by cuts in expenditure and
      after interventions to improve nursing care at a surgical clinic.
AB  - Between 1991 and 1994 the number of beds in the surgical clinic at a central
      hospital in Southern Sweden was cut back by almost 50%. To develop the nursing
      care and to control the effects of the budgetary cuts, an intervention, including
      nursing care development, of an organization that would secure continuity in the
      nurse-patient relationship, individually planned care and quality assurance for
      aspects believed to be crucial to the quality of nursing care was implemented.
      The aim of this study was to analyse patients' satisfaction with surgical nursing
      care between, under and after the last cut in expenditure and the concluded
      intervention. A patient satisfaction questionnaire covering such areas as:
      patient satisfaction with information and decision-making; patient satisfaction
      with contact and the staff-patient relationship; patient satisfaction with ward
      facilities and the physical treatment or examination and patient satisfaction
      with various other aspects of care, was administered (1993 n = 131; 1994 n =
      128). Subsample analysis showed lower scores for patient satisfaction if the
      respondents were women, young, or acutely ill when admitted. While surveys
      carried out between 1991 and 1993 showed an overall improvement in the quality of
      care, as measured by patient satisfaction, it remained at the same level in 1994
      as in 1993, or decreased, regarding patient contacts with staff and physicians,
      involvement in decision-making, anxiety before examination/treatment, anxiety
      regarding professional secrecy, opportunity to influence the solution to their
      physical problems, chance to get sleep without being disturbed, physical nursing
      care and preparations before discharge. Thus a deterioration in quality seemed to
      take place in 1994 indicating that the cuts in expenditure may have been too hard
      and had been made at the expense of patient satisfaction.

PMID- 9154492
TI  - A model to create "organizational readiness" for the successful implementation of
      quality management systems.

PMID- 9154493
TI  - Eight recommendations for maximizing the return on investment in external quality
      oversight.

PMID- 9154494
TI  - Appropriateness of upper gastrointestinal endoscopy: comparison of American and
      Swiss criteria.
AB  - OBJECTIVE: Examine the reproducibility of the RAND method for developing criteria
      for the appropriateness of medical procedures. DESIGN: Comparison of two sets of
      explicit criteria for appropriateness of upper gastrointestinal (UGI) endoscopy,
      developed by separate expert panels from two countries. SETTING: United States,
      Switzerland. STUDY PARTICIPANTS: National experts from different medical
      specialties involved in the referral or application of UGI endoscopy.
      INTERVENTIONS: Each panel was presented with about 500 clinical scenarios
      (indications) that were rated on a nine-point scale as to the appropriateness of
      performing UGI endoscopy for a patient with that clinical presentation. MAIN
      OUTCOME MEASURES: (1) distribution of appropriateness ratings and intrapanel
      agreement categories between the two panels, (2) between-panel agreement of
      assigning appropriateness for comparable indications and, (3) percentage of
      indications with major between-panel differences. RESULTS: Ratings for 2/3 of
      indications could be compared. The Swiss panel showed higher intrapanel agreement
      (54.6% versus 46.2%, P = 0.002). Seventy-eight per cent of comparable indications
      were assigned to identical categories of appropriateness by both panels (kappa =
      0.76, P < 0.001). For 93% of the 376 comparable indications, there were no major
      interpanel differences. CONCLUSION: Separate expert panels in different
      countries, using a standardized methodology, produce criteria for appropriateness
      of medical procedures that are similar. Given the resources being invested
      throughout the world in developing criteria and guidelines, international
      collaboration in seeking optimal use of limited health care resources should be
      intensified.

PMID- 9154495
TI  - Effect of quality of care on preventable perinatal mortality.
AB  - This study assessed and quantified the effect of quality of care on death
      preventability, independent of social and biological variables. One hundred and
      eighty-one avoidable perinatal deaths (cases) were compared to 341 non-avoidable
      ones (controls). Judgement criteria on death preventability were based
      predominantly on compliance with explicit hospital medical care standards,
      determined by peer review. The overall perinatal mortality rate was 24.8 per 1000
      births and could be reduced by 35% if all avoidable perinatal deaths were
      prevented. Sixteen per cent of the deaths presented structural and 31.2% process
      deficiencies; both predominated among avoidable perinatal deaths (35.4% vs 5.3%,
      p < 0.000; and 79.3% vs 5.9%, p < 0.000, respectively). Structural deficiencies
      increased the risk of an avoidable perinatal death eleven-fold (95% confidence
      interval (CI) 4.1, 26.9; p < 0.001) and process deficiencies eighty-eightfold
      (95% CI 37.2, 204.5, p < 0.001), after controlling for confounders. The strength
      of the association between quality of care and preventable perinatal mortality
      was estimated.

PMID- 9154496
TI  - Validation of outcomes through the analysis of the process-outcome relation:
      limitations.
AB  - Validation of outcomes of different levels of neonatal care through the analysis
      of the relationship between process and outcome of care was attempted as part of
      an effectiveness study and quality assurance programme. Adequacy rates and
      outcome measures were calculated for second- and third-level units and centres
      according to the babies' level of risk. Differences in adequacy rates were
      apparently influenced by the differential distribution of babies by care level
      sectors among maternity centres. The comparison of mortality rates for "treated"
      and "untreated" subgroups did not show higher mortality rates for the "untreated"
      subgroups. This finding could be related to the phenomenon of "confounding by
      indication". Consistency of differences in average rates of adequacy with
      differences in general outcomes was observed for most subgroups analysed; lack of
      consistency could be related to low effectiveness. Indications of low
      effectiveness related to secondary and more so to tertiary level technologies
      were observed. The study approach was found more useful for comparisons made at
      the level of maternity services as a whole, where "confounding by indication"
      does not operate than at the level of sectors.

PMID- 9154497
TI  - Comparing results of concurrent and retrospective designs in a hospital
      utilization review.
AB  - Hospital utilization reviews are performed on the basis of lists of explicit
      criteria, such as the Appropriateness Evaluation Protocol, both concurrently and
      retrospectively, in an increasing number of settings as part of efforts to
      improve the performance of hospitals and to reduce health care costs.
      Retrospective data collection has advantages in terms of expenses and ease of
      sampling, but relies on the quality of medical records. We report on a comparison
      between concurrent and retrospective data collection performed simultaneously and
      independently by two reviewers on the same hospital stays in the regional St-Loup
      Hospital. Results suggest that retrospective data collection produces higher
      rates of inappropriate hospital utilization, due to a limited number of criteria
      that are recorded concurrently, but are not found in the retrospective reading of
      medical records. These results should encourage a further investigation of the
      comparability between concurrent and retrospective designs in other settings.

PMID- 9154498
TI  - Assessing the impact of mental health programs upon community: the perspectives
      of primary caregivers and consumers.
AB  - Since 1985, there has been a significant movement in Spanish mental health
      services away from provision of care in psychiatric hospitals and toward a
      community mental health model (CMMH). This reform has ushered in changes not only
      for the patients but also for both their relatives and their primary caregivers.
      However, no survey has ever been carried out to obtain these parties' perceptions
      of the CMMH. Two studies have now been designed to describe the acceptability of
      the CMMH to these two key groups. The goals of the two projects were, firstly, to
      assess the opinions of primary care professionals about CMMH and, secondly, to
      sample the opinions of the patients' relatives regarding mental health care. In
      the first survey, 884 primary caregivers (general practitioners (GPs),
      pediatricians, nurses and social workers) filled out a 14-item questionnaire with
      a five-point response scale. Several aspects of care were evaluated:
      accessibility, referral facilities, therapeutic support, training or teaching
      activities, communication between primary care and mental health professionals
      for their mutual collaboration, and appropriateness of resources. Most of the
      primary caregivers reported that the community psychiatric model improved
      accessibility, treatment and communication between the different levels. Nurses
      and pediatricians reported dissatisfaction with the CMMH. In the second survey,
      the satisfaction of patients' relatives with the services provided by the
      therapists was assessed, using the Satisfaction with Therapist Questionnaire
      (STQ). The STQ consists of 15 items with a three-point response scale. Amount and
      adequacy of the information provided, accessibility, and style of conducting the
      appointment were assessed as measures of satisfaction. A sample of relatives of
      schizophrenic patients was surveyed by mail (76 relatives answered, a response
      rate of 31.13%). In summary, relatives were satisfied with therapists' competence
      but dissatisfied with their communication skills.

PMID- 9154499
TI  - The pattern of health care utilization of elderly people with arthritic pain in
      the hip or knee.
AB  - OBJECTIVE: The aim of the study was to determine the pattern of health care
      utilization of people aged 55-74 years with arthritic pain in the knee or hip.
      DESIGN: People with current pain were identified in a population-based study. A
      filter model was used to describe the pattern of health care utilization of
      people who presented as patients at different levels (GPs or specialist) of the
      health care system in the Netherlands. SETTING: The study was carried out in the
      district of Ommoord in Rotterdam in an age- and gender-representative sample of
      831 (response 83%; n = 691) people. STUDY PARTICIPANTS: A group of 186 people
      with current pain was identified. They completed a questionnaire and were
      interviewed. MAIN OUTCOME MEASURES: Background variables, illness-related
      variables (including radiological osteoarthritis), and self-reported diagnoses
      were described and compared for attenders and non-attenders of GPs and
      specialists. A reference group of patients of GPs was used to determine the
      validity and generalizability of the findings. RESULTS: Eighty-two per cent
      consulted a GP (passed filter 1). In 69% of the GP attenders, 'arthritis' was
      identified (passed filter 2), and 65% of them attended a specialist (passed
      filter 3). People who did not pass the various filters were different from those
      who did with respect to the body mass index (lower; OR 1.24), the chronicity of
      pain (less chronic pain; OR 4.9) and attendance of a physiotherapist (lower; OR
      5.6). The chronicity of pain seems of more importance in determining the health
      care utilization pattern than the severity of pain, the level of disability or
      the presence of radiological osteoarthritis. We suggest that health promotion
      interventions could increase the self-management ability of patients and could
      lower costs.

PMID- 9154500
TI  - Clinical diagnostic accuracy of faecal occult blood test for anal diseases.
AB  - PURPOSE: To investigate the diagnostic accuracy of faecal occult blood test
      (FOBT) for anal diseases and to evaluate the relationship of this disorder to the
      results of FOBT. METHODS: In a hospital-based retrospective study, FOBT using
      faecal samples collected on two consecutive days was performed on patients with
      anal disease, such as internal as well as external haemorrhoids and anal fissure,
      patients with colorectal cancer and healthy subjects to evaluate the diagnostic
      accuracy of FOBT. In a screening-programme-based cross-sectional study, the
      subjects who underwent colorectal cancer screening by FOBT using the 2-day method
      were divided into two groups according to the results of a questionnaire on anal
      diseases; the positive rate of FOBT as well as the predictive value for
      colorectal cancer were determined in the two groups. RESULTS: Among 300 cases,
      including 100 anal diseases, 100 colorectal cancers and 100 healthy subjects, the
      test was positive in 12 anal diseases, 82 colorectal cancers and six healthy
      subjects. The sensitivity to anal diseases and colorectal cancer was calculated
      to be 12% and 82%, respectively, and the specificity was 95%. A significant
      difference was noted in the sensitivity between anal diseases and colorectal
      cancer (P < 0.001). Among 21,724 subjects, who underwent colorectal cancer
      screening, 2395 subjects were positive for anal diseases, and 19,329 subjects
      were negative. The positive rate of FOBT was 7.2 for the anal diseases group and
      6.8 for the non-anal diseases group, and the predictive value for colorectal
      cancer was 2.9 and 3.0, indicating no substantial difference between the two
      groups. CONCLUSIONS: These results reveal that FOBT is inferior for the diagnosis
      of anal diseases, and anal diseases have little relationship to the results of
      FOBT.

PMID- 9154501
TI  - Patient flow analysis in a children's clinic.
AB  - OBJECTIVE: The main objectives of the study were to determine the average waiting
      times of patients at each of the treatment stations in a large paediatric out
      patient department, and to determine the average length of time for a patient
      visit with paediatricians and interns. DESIGN: Data were collected over the
      period of 1 month, from 1 to 31 October 1994, on patient waiting times and length
      of visit with paediatricians and interns. SETTING: The study was conducted in the
      24-h out-patient clinic and the half-day speciality clinic at Qoods Children's
      Teaching Hospital, in Qazvin, Iran. STUDY PARTICIPANTS: All patients attended the
      paediatric out-patient clinic and the half-day speciality clinic during the 24-h
      period for one full month. MAIN OUTCOME MEASURES: The following were measured:
      average waiting times and average length of visit for patients seeing interns and
      paediatricians. RESULTS: The average waiting time to see a paediatrician was
      found to be 77 minutes, and the average length of visit with a paediatrician was
      3.4 minutes. Patients waiting to be seen by interns had an average waiting time
      of 7.8 minutes, and their average length of visit was 7.7 minutes. The average
      length of visit with an intern was higher during the morning (8.6 minutes) and
      highest during the afternoon (9.5 minutes) shifts. Suggestions for improvements
      are made and for ways to take advantage of waiting periods to provide preventive
      and other health care information.

PMID- 9154502
TI  - Testosterone and the aging male.
AB  - The number and magnitude of studies involving testosterone-supplementation
      therapy in older men are limited. In addition, many studies to date have not been
      blinded or controlled, were reported in abstract form only, and had involved a
      variety of androgen-replacement regimens and outcomes measurements. Nonetheless,
      an overview of the data suggests there is real potential for supplementation
      therapy to improve bone mass and muscle mass and strength in this age group.
      Affects on mood, sexual function, and cognition are less clear but may be
      meaningful in certain men. Questions still remain, however, on the magnitude and
      longevity of the beneficial effects of testosterone supplementation in the older
      man and whether only certain subgroups of men would truly benefit from therapy.
      More importantly, the long-term risks of androgen therapy in this age group
      really are not known, especially in the areas of cardiovascular disease and
      prostate diseases. Presently, men who use androgen-supplementation therapy for
      age-related "testosterone deficiency" should consider this as a gamble.

PMID- 9154503
TI  - Sperm separation for gender preference: methods and efficacy.

PMID- 9154504
TI  - Androgenic regulation of NO availability in rat penile erection.
AB  - Prior studies from this laboratory, using untreated castrated (CASTRATE) rats and
      testosterone-treated castrated (TESTO) rats, have shown that the magnitude of the
      intracavernosal pressure increase during erection is androgen dependent. Studies
      from this and other laboratories have also presented evidence suggesting that
      penile erection is mediated principally by nitric oxide (NO). The present report
      was designed to confirm that androgens maintain the availability of cavernosal NO
      and to determine if this androgenic action is exerted at the genomic level
      modulating the expression of the neuronal form of the nitric oxide synthase gene
      (nNOS). The results showed that administration of supplemental L-arginine failed
      to augment the erectile response in either group, suggesting that substrate
      availability is not a cause of the reduced response in CASTRATE animals.
      Inhibition of NO synthesis with a nitro-arginine competitive inhibitor of nitric
      oxide synthase enzyme protein (NOS) resulted in strong inhibition of erection in
      both TESTO and CASTRATE rats. When given in conjunction with ganglionic
      stimulation to induce erection, the NO releasing drug, sodium nitro-prusside
      (SNP), increased intracavernosal pressure in CASTRATE rats but not in TESTO rats,
      suggesting a deficiency of the available NO in CASTRATE-animals. Finally, reverse
      transcription-polymerase chain reaction (RT-PCR) demonstrated that mRNA levels
      for the enzyme nNOS in the penis were greater in TESTO animals than in CASTRATE
      rats. These results support the hypothesis that androgens mediate the erectile
      response in the rat penis by stimulating the expression of the neuronal isoform
      of nitric oxide synthase, thus maintaining an adequate supply of NO.

PMID- 9154505
TI  - Androgen UDP-glucuronyl transferase activity is found primarily in the liver in
      the human.
AB  - In this study, androgen UDP-glucuronyl transferase (UDPGT) activity was
      determined in microsomes of human liver, skin, and prostate. Androgen UDPGT
      activity was highest in the liver microsomes using 5 alpha-androstane-3 alpha, 17
      beta-diol (3 alpha DIOL), androsterone (AN) and dihydrotestosterone (DHT) as
      substrates. The Km and Vmax values and enzyme velocity at the physiological
      concentration of the substrates in the liver microsomes were similar for AN and 3
      alpha DIOL. The values for AN were as follows: Km = 16.9 microM, Vmax = 3.77
      nmol/min/mg protein, and UDPGT velocity = 0.62 pmol/min/mg protein. The values
      for 3 alpha DIOL were as follows: Km = 16.0 microM, Vmax = 5.61 nmol/min/mg
      protein, and UDPGT velocity = 0.42 pmol/min/mg protein. Androgen UDPGT activity
      was lower and showed less affinity for DHT (Km = 23.5 microM, Vmax = 0.84
      nmol/min/mg protein, UDPGT velocity = 0.05 pmol/min/mg protein). No sex or age
      differences in 3 alpha DIOL-UDPGT activity were found in liver microsomes. The
      kinetic parameters and levels of androgen UDPGT activity in the skin and prostate
      samples were not determined because the levels of UDPGT activity were below the
      detection limit for our assay (0.003 pmol/min/mg protein). These results have
      important clinical implications. First, androgen UDPGT activity in the skin and
      prostate is much lower than the activity in the liver, suggesting that these
      tissues are not important sites for conjugation of androgens. Second, androgen
      UDPGT activity in the liver was not altered by sex or age in the 10 samples
      measured from men and women.

PMID- 9154506
TI  - Effects of a 5 alpha-reductase inhibitor, finasteride, on the developing prostate
      and testis of a marsupial.
AB  - This study examines the role of dihydrotestosterone in virilization of the
      developing male tammar. The onset of prostate differentiation in this marsupial
      species normally occurs around 25 days postpartum, long after the onset of
      testicular testosterone production immediately after birth and the appearance of
      5 alpha-reductase in the urogenital sinus before day 10. Males treated with the 5
      alpha-reductase inhibitor Finasteride had reduced prostatic growth and
      development, and their testicular structure was disorganized. Exogenous
      testosterone in males enhanced the development of prostatic buds but also caused
      damage to the testis structure. Treatment of female tammars with testosterone
      between days 20-30 postpartum stimulated prostatic tissue formation and Wolffian
      duct development, confirming that prostatic differentiation is initiated by
      androgens and occurs over a relatively narrow window of time. Testosterone had a
      deleterious effect on the ovary, destroying the germ cells. Although treatment
      with testosterone damaged gonadal cellular structure in both male and female
      tammar young, dihydrotestosterone is apparently necessary for stability of the
      seminiferous tubules in the testis. Taken together, these results suggest that
      dihydrotostesterone initiates prostatic development between days 20 and 25 after
      birth in this marsupial.

PMID- 9154507
TI  - Partial sympathetic denervation of the rat epididymis permits fertilization but
      inhibits embryo development.
AB  - The rat cauda epididymidis receives sympathetic innervation from the inferior
      mesenteric ganglion (IMG). We have previously demonstrated that surgical removal
      of the IMG and proximal hypogastric nerves (IMG denervation) results in
      significant and cauda-specific changes in epididymal sperm transport, sperm
      motility, luminal fluid protein composition, and tissue histology. In the present
      study we used natural mating trials and intrauterine insemination (IUI)
      techniques to determine whether or not IMG denervation affects male fertility and
      reproductive capacity. For the initial studies, adult male Sprague Dawley rats
      were mated with estrous females 1 and 4 weeks following IMG denervation. Nine
      days after mating, uterine implantation sites and corpora lutea (CL) were
      counted. In females mated with sham-operated control males, 85.8% of ovulated
      oocytes were fertilized and subsequently implanted. In contrast, females mated
      with IMG-denervated males 1 or 4 weeks following surgery had 0% and 3.5%,
      respectively, of ovulated oocytes fertilized and implanted. For rats maintained
      21 days after mating, an average of 13 +/- 1 pups were delivered by each of nine
      females mated with sham-operated control male rats; whereas, only seven
      morphologically normal pups were delivered by one of 14 females mated with IMG
      denervated male rats. Additional experiments demonstrated that the decrement in
      offspring was, in part, due to a significant decrease in the number of
      spermatozoa in the female uterus following mating with IMG-denervated males. To
      determine whether IMG denervation exerted an additional effect directly on the
      fertilizing ability of spermatozoa, IUI experiments were performed. Six million
      cauda epididymal spermatozoa from 1- or 4-week IMG-denervated males were
      inseminated into the uterine horns of luteinzing hormone-releasing hormone (LHRH)
      synchronized females and 9 days later implantation sites and CL were counted.
      Implantations were observed for 78%, 28%, and 25% of ovulated oocytes following
      IUI with spermatozoa from sham-operated controls and from 1- and 4-week IMG
      denervated rats, respectively. To determine whether the reduction in implantation
      sites following IUI with spermatozoa from IMG-denervated rats resulted from
      impaired oocyte fertilization, studies were performed in which oocytes were
      retrieved and stained 24 hours after IUI. Comparable fertilization rates of 76.5%
      and 89.0% were observed using cauda epididymal spermatozoa from IMG-denervated
      and sham-operated control males, respectively, indicating that oocyte
      fertilization was not affected by the loss of innervation. These studies
      establish the importance of innervation from the IMG for ejaculatory competence
      and sperm reproductive capacity in the male rat. These data further suggest that
      sympathetic innervation in the epididymis critically influences paternal factors
      associated with embryonic development.

PMID- 9154508
TI  - Discriminant analysis indicates a single sperm protein (SP22) is predictive of
      fertility following exposure to epididymal toxicants.
AB  - In a previous study, we found that ethane dimethanesulphonate (EDS) compromised
      the fertilizing ability of proximal cauda epididymal sperm from the rat within 4
      days of exposure, an effect that persisted in castrated, testosterone (T)
      implanted animals, establishing direct action on the epididymis. This EDS-induced
      reduction in fertilizing ability was highly correlated with a quantitative
      decrease in specific sperm protein. Here we sought to determine whether the
      fertility of proximal cauda epididymal sperm recovered from animals exposed to a
      variety of male reproductive toxicants could be predicted by assessing
      quantitative changes in specific sperm protein(s), or whether more common
      endpoints (e.g., sperm motility, sperm morphology, serum and epididymal tissue T,
      cauda epididymal sperm reserves) also are required to predict fertility. Intact
      adult male rats were dosed with EDS (25 or 50 mg/kg),
      chloroethylmethanesulphonate (CEMS; 12.5 or 18.75 mg/kg), or epichlorohydrin
      (EPI; 3 or 6 mg/kg) daily for 4 days. Castrated, T-implanted rats were dosed with
      hydroxyflutamide (HFLUT; 12.5 or 25 mg/kg) daily for 5 days. On day 5, proximal
      cauda epididymal sperm were inseminated in utero into receptive, cervically
      stimulated adult females, and on day 9, fertility (implants/corpora lutea) was
      assessed. Fertility-was decreased by the higher dose of each toxicant (P < 0.05)
      and also by the lower dose of EPI and HFLUT. Likewise, an acidic 22 kDa sperm
      protein (SP22) was decreased quantitatively (P < 0.05) in silver-stained two
      dimensional gels by the higher dose of each toxicant as well as by the lower dose
      of EPI and HFLUT. Although sperm motility and serum T were altered by specific
      exposures, these endpoints were not useful in predicting fertility. In contrast,
      SP22 was highly correlated (P < 0.0001; r2 = 0.83) with fertility. Indeed, the
      amount of SP22 correctly predicted 90% and 94% of the fertile (> 50% fertility)
      and subfertile (< 50 fertility) animals, respectively, when discriminant analysis
      was performed. Thus, the amount of SP22 in a cauda epididymal sperm sample may be
      a useful predictor of fertility in toxicant-treated animals.

PMID- 9154509
TI  - The PH-20 protein in human spermatozoa.
AB  - PH-20 is a sperm plasma-membrane protein that has been shown to have
      hyaluronidase activity in several mammalian species including nonhuman primates.
      In this investigation, the PH-20 protein was characterized in noncapacitated
      human sperm and in capacitated human sperm. Two forms of PH-20 were observed in
      immunoblots of sodium dodecylsulfate polyacrylamide-gel electrophoresis (SDS
      PAGE) using a polyclonal antibody to recombinant PH-20: a major band of 64 kDa
      appeared in noncapacitated and capacitated sperm extracts and a 53-kDa band that
      appeared only in the acrosome-reaction supernatant of acrosome-reacted sperm.
      Using hyaluronic acid substrate gel analysis, we demonstrated that noncapacitated
      sperm extracts, capacitated sperm extracts, and the acrosome-reaction supernatant
      had hyaluronidase activity at neutral pH (pH 7) and acid pH (pH 4). The 64-kDa
      form in all samples had hyaluronidase activity at both neutral and acid pH, but
      the 53-kDa form was only active at acid pH. Total hyaluronidase activity, as
      measured by a microplate assay, was higher at pH 7 than at pH 4. Very low
      hyaluronidase activity was detected in the acrosome-reaction supernatant.
      Transmission electron microscopy and immunogold labeling showed that PH-20 of
      acrosome-intact human sperm was located on the plasma membrane over the entire
      head but not on the sperm midpiece and tail. After the acrosome reaction, PH-20
      was also located on the inner acrosomal membrane. The biochemical characteristics
      and the ultrastructural localization of PH-20 in human sperm suggest that this
      protein is the human sperm hyaluronidase and, therefore, has an important
      function during fertilization.

PMID- 9154510
TI  - Heat stress causes testicular germ cell apoptosis in adult mice.
AB  - An investigation was undertaken to determine whether the germ-cell loss
      associated with exposure of the testis to abdominal temperature occurs by
      apoptosis. Using an adult-mouse model of experimental unilateral cryptorchidism,
      it was observed that DNA fragmentation, consistent with apoptosis, was observed
      on day 6 in the cryptorchid testis, with subsequent loss of testicular weight,
      histologic evidence of germ-cell loss, and histochemical staining of apoptotic
      germ cells observed on day 7. Vacuolization of the germinal epithelium and the
      appearance of multinucleated giant cells was noted synchronously with the onset
      of germ-cell loss. Histochemical staining for apoptosis was noted most frequently
      among the primary spermatocytes and round spermatids. These results indicate that
      the testicular germ-cell loss observed with exposure to abdominal heat stress
      occurs by apoptosis. Further investigation of the biochemical mechanisms involved
      in testicular apoptosis may provide strategies to address a variety of male
      reproductive issues such as contraception and infertility.

PMID- 9154511
TI  - Early effects of vasectomy on testicular structure and on germ cell and
      macrophage apoptosis in the hamster.
AB  - This study provides quantitative information on the early (up to 3 months)
      effects of vasectomy on apoptosis in the hamster testis. Groups of five adult
      male golden hamsters were either bilaterally vasectomized or sham-operated and
      sacrificed at intervals of 3, 6, and 12 weeks after surgery. In all three
      postvasectomy groups, testis weight and testicular and plasma testosterone (T)
      levels were not different from controls. Spermatogenic alterations, ranging from
      tubules with mild intraepithelial vacuoles to almost completely atrophied
      tubules, were detected in samples of 1 of 5 testes both at 3 and 12 weeks after
      vasectomy. Histometric analysis of testicular tissues at 3, 6, and 12 weeks in
      the postvasectomy groups showed no discernible effect of vasectomy on the
      absolute volumes of seminiferous tubules, tubular lumen, and total Leydig cells
      when compared to respective controls. In situ analysis of germ-cell apoptosis,
      characterized by 3'-end-labeling immunocytochemistry, revealed a significant
      increase (2.5-fold) in germ-cell apoptosis at stages XIII-I, involving primarily
      the dividing spermatocytes after 3 weeks of vasectomy. Apoptotic index was not
      changed from sham-operated animals at 6 and 12 weeks postvasectomy.
      Interestingly, a very high incidence of macrophage apoptosis was detected in the
      samples of three out of five testes in the 12 weeks postvasectomy group (39.3%)
      compared to that of controls (0.8%). These results demonstrate that vasectomy has
      little or no detrimental effect on the morphologic characteristics of the
      spermatogenesis or intratesticular concentrations of testosterone in the majority
      of the animals studied up to 12 weeks postsurgery, although vasectomy transiently
      (3 weeks postsurgery) activated germ-cell apoptosis, involving dividing
      spermatocytes at stages XIII-I.

PMID- 9154512
TI  - Decreased spermatogenesis as the result of an induced autoimmune reaction
      directed against the gonadotropin receptors in male rats.
AB  - The presence of luteinizing hormone (LH) and testosterone is considered critical
      for the maintenance of spermatogenesis in the rat. However, the role and
      importance of follicle-stimulating hormone (FSH) in the initiation and
      maintenance of spermatogenesis has been a subject of debate for some time. The
      objective of this study was to examine the role of FSH and LH in vivo in the
      developing and adult rat by inducing an autoimmune reaction against the receptors
      to these gonadotropins. Sperm numbers were reduced in animals immunized against
      either the FSH or LH receptor (FSHR/LHR). In animals immunized against both FSHR
      and LHR there was also a significant reduction in sperm number although
      spermatogenesis was never completely ablated. These results were seen in male
      rats immunized either prepubertally (18 days of age) or as adults (80 days of
      age). To examine the requirements for FSH in early postnatal-testicular
      development, pregnant females were also immunized against either FSHR, LHR, or
      both of the receptors, and the male offspring were examined at 30 days of age.
      Again, germ-cell number was decreased with the greatest effect in those pups
      whose mothers were immunized against both FSHR and LHR. Radioligand-receptor
      binding assays revealed that the antibody produced in the rats against FSHR was
      able to compete with FSH for binding sites in receptor-membrane preparations.
      Therefore, the mechanism of disruption of spermatogenesis is probably due to
      suppression of hormone to receptor binding. The results of this study support a
      role for FSH in spermatogenesis not only during neonatal and early postnatal
      development but also in the adult animal.

PMID- 9154513
TI  - Impaired germ cell development in the testes of immature rats with neonatal
      hypothyroidism.
AB  - The induction of neonatal hypothyroidism from day 1 to day 25 postpartum using 6
      propyl-2-thiouracil (PTU) resulted in a 45% and 77% reduction of testis weight on
      days 20 and 30, respectively, and an increase in Sertoli cell number. The present
      study evaluated the effect of neonatal hypothyroidism on the developing germ cell
      population during the first 30 days postnatally. Qualitative and quantitative
      studies using the optical disector method were undertaken on the testes of
      control and hypothyroid rats, on days 10, 20, and 30 after birth. Germ cell
      development was obviously impaired in the hypothyroid rats, as shown by decreased
      primary spermatocyte and round spermatid numbers in day 20 and day 30 testes, and
      the persistence of gonocytes on days 10 and 20. These reductions obviously
      accounted for the reduced testis weight, absolute volume, and diameter of the
      seminiferous cords/tubules, especially on days 20 and 30. The failure to
      establish a seminiferous tubule lumen in hypothyroid rats probably reflects
      decreased fluid production and a functional immaturity of the Sertoli cells. The
      delay in germ cell maturation and increased degeneration may be because of the
      immature state of the Sertoli cell or result from the low follicle-stimulating
      hormone and thyroxine levels known to occur in the hypothyroid rats.

PMID- 9154514
TI  - Effects of psychological stress on human semen quality.
AB  - We investigated the relationship between psychological stress and sperm
      concentration, motility, and morphometry in a prospective study of 157 volunteers
      who were enrolled in a prepaid health plan. We measured psychological job stress
      and life-event stress by telephone interview. Sperm-kinematic and nuclear
      morphometric variables were measured using computer-assisted image analyses.
      Sperm concentration, percent motility, and semen volume were determined by
      objective visual methods. We performed multiple linear regression for each semen
      variable to examine its relationship to stress, controlling for potential
      confounders. Stress at work and total number of life events were not related to
      differences in semen quality. However, the recent death of a close family member
      was associated with a reduction in straight-line velocity (P = 0.002) and percent
      of progressively motile sperm (P = 0.02); it was also marginally associated with
      an increase in the fraction of sperm with larger and more tapered nuclei. These
      findings suggest that the fecundity of men experiencing the stress of a family
      member's death might be temporarily diminished.

PMID- 9154515
TI  - Spermatids from mice after cryptorchid and reversal operations can initiate
      normal embryo development.
AB  - We investigated fertilization and embryo development following intracytoplasmic
      injection of round spermatids collected from mice after cryptorchid and reversal
      operations. The rates of oocyte activation, blastocyst formation, and development
      to live offspring were compared after intracytoplasmic injection of round
      spermatids from intact, cryptorchid males (control) or males that had undergone
      the reversal operation. The incidence of normal fertilization and embryo
      development was about the same when the oocytes were injected with spermatids
      from intact cryptorchid males or males after reversal operation. The rates of the
      development of two-cell embryos to term were also about the same, regardless of
      the origin of spermatids injected. Round spermatids from both cryptorchid and
      previously cryptorchid testes can initiate normal embryo development when
      injected into mature oocytes.

PMID- 9154516
TI  - Manidipine improves spermatogenesis in the stroke-prone spontaneously
      hypertensive rat.
AB  - We evaluated the protective effects of manidipine, which is a long-lasting
      calcium-channel blocker, against damage to spermatogenesis arising from
      hypertensive vascular changes in stroke-prone spontaneously hypertensive rats
      (SHRSP). SHRSP showed severe hypertension at 11 weeks of age, followed by
      hypertensive changes in intratesticular arterioles from 15 weeks of age.
      Manidipine lowered the blood pressure and the hypertensive vascular changes of
      intratesticular arterioles in SHRSP. The percentages of atrophic seminiferous
      tubules and tubules with less-differentiated germ cells were increased in SHRSP
      at 23 weeks of age, although the administration of manidipine preserved
      spermatogenesis at a normal level. The transferrin concentration in testicular
      cytosol was comparable, whereas insulin-like growth factor-I (IGF-I) was reduced
      from 19 weeks of age in SHRSP. Manidipine preserved the normal IGF-I
      concentration. Therefore, manidipine prevented the development of hypertensive
      vascular changes in the testis and maintained normal Sertoli cell function. As a
      result, manidipine protected spermatogenesis in SHRSP. These findings also
      suggested that hypertensive vascular changes in the testes play the most
      important role in spermatogenic damage in SHRSP.

PMID- 9154517
TI  - Computerized imaging and scanning electron microscope (SEM) analysis of co
      cultured fresh and frozen bovine sperm.
AB  - Fresh and frozen-thawed bull sperm were incubated with bovine oviductal
      epithelial cells and segments from the oviducts to examine the usefulness of
      these culture systems to model sperm changes in vivo. Changes in sperm motion
      characteristics [computer-assisted sperm analysis (CASA)] and surface morphology
      [scanning electron microscopy (SEM)] were evaluated. In Experiment 1, fresh and
      frozen sperm were suspended in the Brackett and Oliphant medium or modified
      Tyrodes medium (mTALP) and incubated for 0, 3, 6, and 9 hours in direct contact
      with bovine oviductal-epithelial cell (BOEC) monolayers prepared from oviducts of
      cows in the periovulatory phase of estrus. The percentage of motile sperm
      decreased gradually in mTALP, but decreased rapidly in Brackett's defined medium
      after 3 hours of incubation, with overall averages of 55 and 32%, respectively.
      The percentage of motile fresh sperm exceeded frozen-thawed sperm under all
      conditions. In Experiment 2, sperm suspended with mTALP were incubated in dishes
      without monolayers (control), with monolayers, and within the segments of the
      oviduct for 0, 3, and 6 hours. In the epithelial cell monolayers, the percentage
      of motile sperm was similar to the controls throughout incubation, but after 3
      hours in the oviductal segments, a decrease, partly associated with more rapid
      rupture of acrosomal membranes occurred. Sperm velocity was higher (100
      microns/second) in fresh sperm than in frozen sperm (85 microns/second).
      Acrosomal changes, discernible with SEM after 3 hours of incubation, increased
      with time and were always found more often in frozen than in fresh sperm. The
      BOEC-monolayer system provided a useful in vitro model to study pre-fertilization
      changes in sperm.

PMID- 9154518
TI  - Oscillatory mechanisms in pairs of neurons connected with fast inhibitory
      synapses.
AB  - We study dynamical mechanisms underlying oscillatory behavior in reciprocal
      inhibitory pairs of neurons, using a two-dimensional cell model. We introduce one
      and-two dimensional phase portraits to illustrate the behaviors, thus reducing
      the study of dynamical mechanisms to planar geometrical properties. We examined
      whether other mechanisms besides the escape and release mechanisms (Wang and
      Rinzel, 1992) might be needed for some cases of reciprocal inhibition, and show
      that, within the confines of a simple two-dimensional cell model, escape and
      release are sufficient for all cases. We divided the behaviors of a single cell
      into six different types and examined the joint behaviors arising from every
      combination of pairs of cells with behaviors drawn from these six types. For the
      case of two quiescent cells or two cells each having plateau potentials,
      bifurcation diagrams demonstrate the relations between synaptic threshold and
      synaptic strength necessary for oscillations by escape, oscillations by release,
      or network-generated plateau potentials. Thus we clarify the relationship between
      plateau potentials and oscillations in a cell. Using the two dimensional cell
      model we examine 1:N beating between cells and find that our simple model
      displays many of the essential dynamical properties displayed by more
      sophisticated models, some of which relate to thalamocortical spindling.

PMID- 9154519
TI  - Synchronous bursting can arise from mutual excitation, even when individual cells
      are not endogenous bursters.
AB  - Mutual excitation between two neurons is generally thought to raise the
      excitation level of each neuron or, if they are both bursty, to act to
      synchronize their bursts. If only one is bursty, it can induce synchronized
      bursts in the other cell. Here we show that two nonbursty cells can be induced to
      burst in synchrony by mutual excitatory synaptic connections, provided the
      presynaptic threshold for graded synaptic transmission at each synapse is at a
      different level. This mechanism may operate in a recently discovered network in
      the lobster Homarus gammarus. By a duality between presynaptic threshold and
      injected current, we also show that two identical, nonbursty, mutual excitatory
      cells could be induced to burst in synchrony by injecting differing amounts of
      current in the two cells. Finally we show that differential oscillations between
      two mutual excitatory cells could be stopped by a slow-tailed hyperpolarizing
      current pulse into one cell or a slow-tailed depolarizing pulse into the other.

PMID- 9154520
TI  - Simulation of gamma rhythms in networks of interneurons and pyramidal cells.
AB  - Networks of hippocampal interneurons, with pyramidal neurons pharmacologically
      disconnected, can generate gamma-frequency (20 Hz and above) oscillations.
      Experiments and models have shown how the network frequency depends on excitation
      of the interneurons, and on the parameters of GABAA-mediated IPSCs between the
      interneurons (conductance and time course). Here we use network simulations to
      investigate how pyramidal cells, connected to the interneurons and to each other
      through AMPA-type and/or NMDA-type glutamate receptors, might modify the
      interneuron network oscillation. With or without AMPA-receptor mediated
      excitation of the interneurons, the pyramidal cells and interneurons fired in
      phase during the gamma oscillation. Synaptic excitation of the interneurons by
      pyramidal cells caused them to fire spike doublets or short bursts at gamma
      frequencies, thereby slowing the population rhythm. Rhythmic synchronized IPSPs
      allowed the pyramidal cells to encode their mean excitation by their phase of
      firing relative to the population waves. Recurrent excitation between the
      pyramidal cells could modify the phase of firing relative to the population
      waves. Our model suggests that pools of synaptically interconnected inhibitory
      cells are sufficient to produce gamma frequency rhythms, but the network behavior
      can be modified by participation of pyramidal cells.

PMID- 9154521
TI  - How does the crayfish swimmeret system work? Insights from nearest-neighbor
      coupled oscillator models.
AB  - Rhythmic movements of crayfish swimmerets are coordinated by a neural circuit
      that links their four abdominal ganglia. Each swimmeret is driven by its own
      small local circuit, or pattern-generating module. We modeled this network as a
      chain of four oscillators, bidirectionally coupled to their nearest neighbors,
      and tested the model's ability to reproduce experimentally observed changes in
      intersegmental phases and in period caused by differential excitation of selected
      abdominal ganglia. The choices needed to match the experimental data lead to the
      following predictions: coupling between ganglia is asymmetric; the ascending and
      descending coupling have approximately equal strengths; intersegmental coupling
      does not significantly affect the frequency of the system; and excitation affects
      the intrinsic frequencies of the oscillators and might also change properties of
      intersegmental coupling.

PMID- 9154522
TI  - The role of axonal delay in the synchronization of networks of coupled cortical
      oscillators.
AB  - Coupled oscillator models use a single phase variable to approximate the voltage
      oscillation of each neuron during repetitive firing where the behavior of the
      model depends on the connectivity and the interaction function chosen to describe
      the coupling. We introduce a network model consisting of a continuum of these
      oscillators that includes the effects of spatially decaying coupling and axonal
      delay. We derive equations for determining the stability of solutions and analyze
      the network behavior for two different interaction functions. The first is a sine
      function, and the second is derived from a compartmental model of a pyramidal
      cell. In both cases, the system of coupled neural oscillators can undergo a
      bifurcation from synchronous oscillations to waves. The change in qualitative
      behavior is due to the axonal delay, which causes distant connections to
      encourage a phase shift between cells. We suggest that this mechanism could
      contribute to the behavior observed in several neurobiological systems.

PMID- 9154523
TI  - The role of inhibition in an associative memory model of the olfactory bulb.
AB  - The external plexiform layer is where the interactions between the mitral
      (excitatory) and granule (inhibitory) cells of the olfactory bulb (OB) take
      place. Two outstanding features of these interactions are that they are
      dendrodendritic and that there seem to be none between excitatory cells. The
      latter are usually credited with the role of forming Hebbian cell assemblies.
      Hence, it would seem that this structure lacks the necessary ingredients for an
      associative memory system. In this article we show that in spite of these two
      properties this system can serve as an associative memory. Our model incorporates
      the essential anatomical characteristics of the OB. The memories in our system,
      defined by Hebbian mitral assemblies, are activated via the interactions with the
      inhibitory granule cells. The nonlinearity is introduced in our model via a
      sigmoid function that describes neurotransmitter release in reciprocal
      dendrodendritic synapses. The capacity (maximal number of odors that can be
      memorized) depends on the sparseness of coding that is being used. For very low
      memory activities, the capacity grows as a fractional power of the number of
      neurons. We validate the theoretical results by numerical simulations. An
      interesting result of our model is that its capacity increases as a function of
      the ratio of inhibitory to excitatory populations. This may provide an
      explanation for the dominance of inhibitory cells in the olfactory bulb.

PMID- 9154524
TI  - Bridging Schwann cell transplants promote axonal regeneration from both the
      rostral and caudal stumps of transected adult rat spinal cord.
AB  - Transplantation of cellular components of the permissive peripheral nerve
      environment in some types of spinal cord injury holds great promise to support
      regrowth of axons through the site of injury. In the present study, Schwann cell
      grafts were positioned between transected stumps of adult rat thoracic spinal
      cord to test their efficacy to serve as bridges for axonal regeneration. Schwann
      cells were purified in culture from adult rat sciatic nerve, suspended in
      Matrigel: DMEM (30:70), and drawn into polymeric guidance channels 8 mm long at a
      density of 120 x 10(6) cells ml-1. Adult Fischer rat spinal cords were transected
      at the T8 cord level and the next caudal segment was removed. Each cut stump was
      inserted 1 mm into the channel. One month later, a bridge between the severed
      stumps had been formed, as determined by the gross and histological appearance
      and the ingrowth of propriospinal axons from both stumps. Propriospinal neurons
      (mean, 1064 +/- 145 SEM) situated as far away as levels C3 and S4 were labelled
      by retrograde tracing with Fast Blue injected into the bridge. Near the bridge
      midpoint there was a mean of 1990 +/- 594 myelinated axons and eight times as
      many nonmyelinated, ensheathed axons. Essentially no myelinated or unmyelinated
      axons were observed in control Matrigel-only grafts. Brainstem neurons were not
      retrogradely labelled from the graft, consistent with growth of immunoreactive
      serotonergic and noradrenergic axons only a short distance into the rostral end
      of the graft, not far enough to reach the tracer placed at the graft midpoint.
      Anterograde tracing with PHA-L introduced rostral to the graft demonstrated that
      axons extended the length of the graft but essentially did not leave the graft.
      This study demonstrates that Schwann cell grafts serve as bridges that support
      (1) regrowth of both ascending and descending axons across a gap in the adult rat
      spinal cord and (2) limited regrowth of serotonergic and noradrenergic fibers
      from the rostral stump. Regrowth of monoaminergic fibres into grafts was not seen
      in an earlier study of similar grafts placed inside distally capped rather than
      open-ended channels. Additional intervention will be required to foster growth of
      the regenerated axons from the graft into the distal cord tissue.

PMID- 9154525
TI  - Coexpression of connexin45 and -32 in oligodendrocytes of rat brain.
AB  - Connexin proteins are the subunits of gap junction channels, and are encoded by a
      gene family. Although several connexin mRNAs were detected in brain, only a few
      connexin-proteins have been localized to specific cell types in this tissue. Here
      we describe expression of connexin45 protein in oligodendrocytes in rat
      hippocampus. Double immunofluorescent staining using specific antibodies to
      connexin45 and connexin32 paired with cell-type specific marker proteins revealed
      that connexin45 and connexin32 were co-expressed and colocalized in
      oligodendrocytes. Each of the connexin antibodies gave rise to the same pattern
      of punctate fluorescence in the plasma membrane of cell bodies and proximal
      processes of oligodendrocytes. Connexins in the plasma membrane of
      oligodendrocytes may form gap junctions between oligodendrocytes, or between
      oligodendrocytes and astrocytes. Expression of connexin45 in oligodendrocytes may
      prevent dysmyelinating effects of connexin32 mutations in the central nervous
      system of Charcot-Marie-Tooth (X-type) patients.

PMID- 9154526
TI  - Developmental regulation of interstitial cell density in bullfrog skeletal
      muscle.
AB  - Denervation of skeletal muscle results in striking connective tissue remodelling
      in junctional areas of muscle. Since extracellular matrix molecules mediate
      axonal growth and synaptic differentiation, it is likely that the interstitial
      cells and matrix molecules that accumulate near synaptic sites after denervation
      influence the regrowth and regeneration of synaptic connections. The experiments
      presented here addressed the question of whether the junctional connective tissue
      in developing bullfrog skeletal muscle was also specialized in its cellular and
      molecular composition. Denervation responses of muscle, such as extrajunctional
      sensitivity to acetylcholine, often reproduce the characteristics of developing
      muscle during synaptogenesis. In developing muscle, the distribution of
      interstitial cells was nonuniform during the period of muscle fibre birth and
      synaptogenesis. Interstitial cells were concentrated near synaptic sites as in
      denervated adult muscle. Unlike denervated adult muscle, there were no junctional
      accumulations of fibronectin or tenascin, matrix molecules produced by
      interstitial cells, in developing muscles. These results demonstrate that the
      junctional connective tissue in developing muscle is identified by a high density
      of interstitial cells that may play a role in the identification and formation of
      synaptic sites. Further, the junctional matrix environment of developing muscle
      is distinct from the matrix remodelling that occurs in response to denervation,
      suggesting that the matrix production by interstitial cells during development is
      regulated differently from that after denervation of the neuromuscular junction.

PMID- 9154527
TI  - Combined retrograde tracing and immunohistochemistry of trigeminal ganglion
      neurons projecting to gingiva or tooth pulps in the lower jaw of the cichlid
      Tilapia mariae.
AB  - Rat trigeminal ganglion neurons projecting to the oral mucosa or to tooth pulps
      have different cell diameters and contain different chemical markers. In the
      present paper we examine whether trigeminal ganglion neurons sending axons to
      gingiva or tooth pulps in the lower jaw of the cichlid Tilapia mariae differ in a
      similar way. Retrograde tracing with fluorescent latex microspheres revealed
      labelled gingival and pulpal neurons in the caudal part of the trigeminal
      ganglion. The gingival neurons had a unimodal size distribution (peak 11 microns;
      range 8-14 microns) and the pulpal neurons exhibited a bimodal size distribution
      (peaks 12 and 25 microns; range 10-40 microns). Immunohistochemistry revealed a
      calcitonin gene-related peptide-like immunoreactivity in some 40% of the gingival
      neurons and a substance P-like immunoreactivity in 30%. Of the small pulpal
      neurons about 60% exhibited a calcitonin gene-related peptide-like
      immunoreactivity and 15% showed a substance P-like immunoreactivity. Of the large
      pulpal neurons some 70% exhibited a calcitonin gene-related peptide-like
      immunoreactivity. These neurons did not show a substance P-like immunoreactivity.
      In some animals a few trigeminal ganglion neurons showed a neuropeptide Y- or a
      vasoactive intestinal polypeptide-like immunoreactivity. Perikarya with a
      tyrosine hydroxylase- or a choline acetyl transferase-like immunoreactivity were
      not observed. We conclude that gingiva and tooth pulps in the lower jaw of T.
      mariae are innervated by trigeminal ganglion neurons, the cell diameters and
      neuropeptide contents of which differ in a pattern similar to that in the rat.
      Hence, this seems to represent a conserved evolutionary pattern.

PMID- 9154528
TI  - Axon-glial relationships in early CNS-PNS transitional zone development: an
      ultrastructural study.
AB  - The CNS-PNS transitional zone of rat cervical ventral rootlets develops in two
      stages: first, axon segregation, then transitional node formation. This
      ultrastructural study examines the former. Material was prepared by standard
      methods. Shortly after they grow out from the neural tube, ventral motoneuron
      axon bundles are extensively segregated by a matrix of fine processes forming a
      barrier across the rootlet, just distal to the cord surface. These processes
      arise from cell clusters on the rootlet surface. This barrier is prominent until
      the period around birth, when it is replaced by a second in which the axons are
      completely segregated from one another. The perikarya and processes forming this
      barrier resemble those of the first, but lie at or just below the cord surface.
      Thus, beginning at the earliest stage, a barrier crosses the axon bundle and
      segregates its axons before axon segregation is advanced either in the PNS or
      (especially) in the CNS. This may prevent central Schwann cell migration.
      Evidence is presented suggesting that the second barrier may arise through a
      relative proximal relocation of the first, as the cord grows radially. Near the
      cord surface, a complete, funnel-shaped sleeve of glial processes surrounds the
      axon bundle. This is continuous at the cord surface with the glia limitans. It
      constitutes an integral part of the transitional zone apparatus. It is also
      continuous centrally with the sheath which enfolds the bundle of ventral
      motoneuron axons as they run between the ventral horn and the transitional zone.
      Axon segregation at the cord surface, and therefore the formation of the
      definitive astrocytic CNS-PNS barrier occur relatively (and perhaps surprisingly)
      late at the cord surface. The definitive sharp discontinuity of central and
      peripheral tissue types characteristic of the transitional zone is established
      only after birth.

PMID- 9154529
TI  - Photoreceptor number and outer segment disk membrane surface area in the retina
      of the rat: stereological data for whole organ and average photoreceptor cell.
AB  - A random sampling scheme is employed to obtain stereological estimates of disk
      membrane surface area in the entire retina and in the average photoreceptor cell.
      The scheme involves the use of vertical sections with combined light and electron
      microscopy at several magnification levels. Left and right retinas from six
      albino animals were analysed. There were no significant lateral differences. On
      average, the retina had a volume of 16 mm3, thickness of 200 microns and surface
      area of 80 mm2 (representing about 56% of the external surface of the eyeball).
      Photoreceptor disk membranes within outer segments amplified total retinal
      surface by almost 1000-fold (final surface 770 cm2 per retina). The retina
      contained 3 x 10(7) photoreceptors (packing density 374,000 mm-2) with an average
      disk membrane surface area of 2600 microns2. Mean nuclear volume in photoreceptor
      cells was 59 microns3 and the coefficient of variation for the distribution of
      nuclear volumes was 57%. The data are consistent with an average of 700 disks per
      photoreceptor cell, a membrane area of 4 microns2 per disk and a convergence
      ratio of approximately 260 photoreceptors per optic nerve fibre. The basic scheme
      could be modified for other species and for direct cell counts conducted on rods
      and cones separately.

PMID- 9154530
TI  - Effect of consecutively applied fluorescein eye drops on corneal and aqueous
      concentrations of fluorescein.
AB  - The main objective of this study was to determine the intraocular concentration
      of fluorescein after applying five eye drops with only 1-min intervals in human
      eyes. The concentration of fluorescein in corea and aqueous was studied with
      fluorophotometry in 11 healthy volunteers. Five 10-microliter drops of 2%
      fluorescein solution were administered with 1-min intervals, and the intraocular
      concentrations that were achieved were compared with those obtained with just one
      eye drop. Five consecutive fluorescein drops caused a 2.6- to 3.1-fold increase
      in fluorescein concentrations of the anterior chamber 1-8 h after application
      compared with a single eye drop (p < 0.05). Corresponding values for the cornea
      were 2.1-2.8. As a conclusion, administration of five eye drops applied
      consecutively significantly increases intraocular drug concentration during 8 h
      in humans.

PMID- 9154531
TI  - Effects of mucin ophthalmic solution on epithelial wound healing in rabbit
      cornea.
AB  - To test the hypothesis that a mucin ophthalmic solution could accelerate the
      healing of corneal epithelium, we conducted a study in rabbits using an
      ophthalmic solution containing mucin extracted from bovine submaxillary gland.
      The corneas of rabbits were abraded with a razor blade in the central portion
      over an area demarcated with a 7-mm trephine. Mucin-containing eye drops were
      instilled into the right eye 4 times a day for 3 days, and the vehicle was
      instilled into the left eye. After enucleation, the eyes were observed by
      scanning and transmission electron microscopy as well as light microscopy. Mucin
      containing eye drops were shown to reduce the epithelial defect area more rapidly
      than the vehicle. Thus, the eye drops accelerated corneal epithelial wound
      healing.

PMID- 9154532
TI  - Influence of tissue sample dimensions on the swelling of the corneal stroma.
AB  - The kinetics of imbibition of unbuffered 1% NaCl at 37 degrees C by whole ovine
      corneal stroma preparations were compared to those for square samples of stromas
      with side dimensions of 4, 6, 8, 10 and 13 mm. The rates and extent of swelling
      over a 24-hour period were proportionately greater for samples with smaller
      dimensions. After 24 h, the relative magnitude of the changes in wet mass ranged
      from 465% for complete stromas to 1,185% for 4 x 4-mm tissue squares. This size
      dependent difference in swelling may, in part, account for differences between
      previous studies.

PMID- 9154533
TI  - In vitro UV-B effect on lens protein solutions.
AB  - To investigate the effects of UV-B exposure on the protein solutions of different
      lens parts, rabbit lenses were separated into the equator (Eq), anterior cortex
      (Ac), nucleus (Nu) and posterior cortex (Pc). After homogenization, the water
      soluble protein from each part was irradiated with UV-B at 0 to 0.225 J/cm2.
      Alterations in the content of protein SH, carbonyl groups, light scattering
      intensity and SDS-PAGE pattern were measured to compare the effect of UV-B on the
      protein solutions of various lens parts with or without additional GSH to test
      its preventive effect. The results showed that after UV-B irradiation, the
      protein sulfhydryl groups are gradually reduced. The nonprotein thiol (GSH added
      to the protein solution) was lost more rapidly than the protein sulfhydryl. The
      high molecular bands on the SDS-PAGE pattern mainly aggregated with disulfide. UV
      B damage also increased the content of carbonyl groups and light scattering,
      irrespective of the lens parts. Lens proteins from the equator suffered the least
      damage while those of the nucleus were most strongly affected by UV-B exposure.
      This study suggests that the lens proteins from various lens parts have different
      responses to UV-B exposure; the sensitivity was in the following order: Eq < Ac <
      or = Pc < Nu.

PMID- 9154534
TI  - Possible mechanism of exacerbating cataract formation in cataractous human lens
      capsules induced by systemic hypertension or glaucoma.
AB  - To clarify the role of the lens capsule in cataract formation, changes in the
      protein conformational structure of immature cataractous lens capsules from
      patients with systemic hypertension or glaucoma have been investigated, as
      compared to normal lens capsules. The protein secondary structure and composition
      of these capsular samples were determined using Fourier transform infrared
      microspectroscopy with second-derivative, deconvolution and curve-fitting
      methods. We found that the composition of both random coil and beta-type (beta
      sheet and beta-turn) structures in the immature cataractous human lens capsules
      was increasingly induced by systemic hypertension or glaucoma, but alpha-helix
      content clearly decreased, leading to the alteration of protein conformational
      structures in lens capsules. A possible pathway of cataract formation exacerbated
      by systemic hypertension or glaucoma is discussed. According to the results, we
      propose that systemic hypertension or glaucoma induce changes in the protein
      conformational structures of the lens capsule, then cause alteration of membrane
      transport and permeability for ions, and finally increase intraocular pressure,
      resulting in the exacerbation of cataract formation. The effect on the
      conformational structure of cataractous human lens capsules is more pronounced
      for systemic hypertension than for glaucoma. The present study implies that
      systemic hypertension or glaucoma can exacerbate cataract formation in senile
      patients by modifying the protein secondary structures in the lens capsule.

PMID- 9154535
TI  - In vitro effects of doxorubicin and mitomycin C on human Tenon's capsule
      fibroblasts.
AB  - Doxorubicin is an antiproliferative agent, that also inhibits prolyl 4
      hydroxylase in vitro. We evaluated the effects of doxorubicin and mitomycin C
      (MMC) on the proliferation of human Tenon's capsule fibroblasts and the secretion
      of type I collagen in these cells to explore the potential use of doxorubicin as
      an antifibrotic agent after glaucoma filtering surgery. Standard immunoassays
      were used to determine the concentrations of type I procollagen COOH-terminal
      peptide (PIP), laminin and vitronectin receptor in conditioned media and cell
      lysates in the presence or absence of doxorubicin or MMC. The mitotic activity
      and viability of these cells were also determined. Cellular ultrastructure was
      evaluated by transmission electron microscopy. Doxorubicin and MMC decreased the
      cellular viability, the mitotic activity, and the production of the peptides
      measured. The inhibition of PIP secretion into the culture medium was higher in
      doxorubicin-treated cultures than in MMC-treated cultures at the tested
      concentrations (5-100 microM). The decrease in PIP levels in cell lysates was
      less in doxorubicin-treated culture (25 microM) than in MMC-treated culture (25
      microM), suggesting that procollagen synthesis and secretion might be attenuated
      by doxorubicin. Ultrastructural studies revealed increased numbers of lysosomes
      in the cytoplasm of doxorubicin-treated cells relative to MMC-treated cells.
      Doxorubicin and MMC reduced cell viability and inhibited the proliferation and
      synthesis of PIP, laminin, and vitronectin receptor peptide. Inhibitory effects
      of doxorubicin on PIP secretion were more potent than those of MMC. Doxorubicin
      may be useful for inhibiting the fibrotic response at the site of ocular
      filtering surgery.

PMID- 9154536
TI  - Flow cytometric analysis of surface antigens on human conjunctival epithelial
      cells.
AB  - We analyzed the levels of expression of different surface adhesion molecules on
      normal human conjunctival epithelial cells with cytology and flow cytometry. The
      levels of beta 1 (CD29), VLA-1 (CD49a), VLA-2 (CD49b), and VLA-3 (CD49c)
      integrins were high, whereas those of VLA-5 (CD49e) and VLA-6 (CD49f) were faint,
      and that of VLA-4(CD49d) was undetectable. Among the beta 2 integrins, the levels
      of Mac-1 (CD11b) and p150.25(CD11c) were positive, while LFA-1 (CD11a) was not
      detectable. HLA class I and class II were also expressed. However, CR2 (CD21),
      CD57, CD44 and ICAM-1 (CD54) were not detected. Our study suggests that these
      techniques may aid in identifying changes in the expression levels of various
      surface antigens on conjunctival epithelial cells that could occur in ocular
      surface disease.

PMID- 9154537
TI  - Diurnal variations in intraocular pressure in the albino rabbit: relationship to
      morning intraocular pressure.
AB  - Intraocular pressure (IOP) measurements were carried out in 88 adult male New
      Zealand white rabbits. IOP of each rabbit was measured in the morning (8.00-9.00
      h), at noon (12.00-13.00 h) and in the afternoon (16.00-17.00 h) on 6 separate
      days. A linear relationship was found between the noon IOP and the morning IOP:
      noon IOP = 0.77 morning IOP + 4.37; r = 0.950. This regression line intersects
      the line of IOP equality (morning IOP = noon IOP) at morning IOP = 19 mm Hg.
      Thus, in animals with morning IOP < 19 mm Hg, there was an increase in IOP
      between the morning and noon readings whereas animals with a higher morning IOP
      (20-30 mm Hg) showed a progressive decrease in the morning-noon IOP. This
      observed relationship explains the disparity among previously published IOP
      diurnal curves for rabbits. It is suggested that future studies of IOP changes
      should present IOP values and not only relative changes in IOP (delta IOP or
      percent change in IOP).

PMID- 9154538
TI  - Equivalent efficacy and reduced occurrence of diarrhea from a new formulation of
      amoxicillin/clavulanate potassium (Augmentin) for treatment of acute otitis media
      in children.
AB  - OBJECTIVE: To compare the safety and efficacy, in treating acute otitis media
      (AOM) in children, of a new formulation of amoxicillin/clavulanate potassium
      (Augmentin) oral suspension providing 45/6.4 mg/kg/day and administered twice
      daily (bid) for 5 and 10 days, respectively, with the safety and efficacy of the
      original formulation providing 40/10 mg/kg/day and administered three times daily
      (tid) for 10 days. STUDY DESIGN: Eight hundred sixty-eight children ages 2 months
      to 12 years with AOM were randomly assigned to one of the three treatment groups.
      Stringent criteria were used for the diagnosis of AOM and for determinations of
      "cure" and "improvement." Subjects were reexamined on Days 12 to 14 and 32 to 38.
      RESULTS: Among subjects whose treatment and follow-up conformed fully to
      protocol, the proportion of treatment successes (clinically cured or improved) on
      Days 12 to 14 was 78.8% (149 of 189) in the tid 10-day group, 86.5% (154 of 178)
      in the bid 10-day group and 71.1% (140 of 197) in the bid 5-day group.
      Corresponding values on Days 32 to 38 were 64.2% (95 of 148) in the tid 10-day
      group, 63.1% (94 of 149) in the bid 10-day group and 57.8% (93 of 161) in the bid
      5-day group. None of the differences between the tid 10-day regimen and either of
      the 2 bid regimens were statistically significant, but the bid 10-day regimen was
      significantly more effective than the bid 5-day regimen in younger subjects. In
      the study population as a whole, results were similar to those in per protocol
      subjects. Overall the incidence of protocol-defined diarrhea was 26.7% (74 of
      277) in the tid 10-day group, compared with 9.6% (27 of 280) in the bid 10-day
      group (P < 0.0001) and 8.7% (25 of 286) in the bid 5-day group (P < 0.0001).
      CONCLUSIONS: In comparison with the original formulation of Augmentin
      administered tid for 10 days in the treatment of AOM in children, the new
      formulation administered bid for 10 days provides at least equivalent efficacy
      and causes substantially less diarrhea. Administration for 5 days appears not to
      provide equivalent efficacy, but the difference appears limited to younger
      children and the margin of difference is small.

PMID- 9154539
TI  - Cefprozil treatment of persistent and recurrent acute otitis media.
AB  - OBJECTIVE: We identified the pathogens causing persistent and recurrent acute
      otitis media (AOM) and the clinical efficacy of cefprozil as treatment. STUDY
      DESIGN: This was a noncomparative, open label multicenter trial. Children ages 6
      months to 12 years with signs and symptoms of AOM and evidence of middle ear
      effusion, as confirmed by pneumatic otoscopy or tympanometry, underwent
      tympanocentesis and subsequent treatment with cefprozil (15 mg/kg given twice
      daily) for 10 days. Patients with recurrent otitis media or failure of previous
      antibiotic therapy or prophylaxis were particularly sought for the study.
      RESULTS: Two hundred sixty-two (99%) of 265 enrolled children were considered
      evaluable. The median age of the study group was 1 year. Ninety-eight (37%) of
      the children had a history (within 30 days) of prior antibiotic use. Ninety-seven
      (37%) met our definition of recurrent AOM, 48 (18%) met our definition of
      persistent AOM and 132 (50%) children had 3 or more previous episodes of acute
      otitis media within 12 months before study. Eighty-two (31%) of the enrollment
      tympanocentesis had no growth, 150 (57%) had a single bacterial pathogen and 29
      (11%) had multiple bacterial pathogens. Of the 93 Streptococcus pneumoniae
      pretreatment isolates, 50 (54%) were penicillin-susceptible, 12 (13%) were
      penicillin-intermediate resistant and 31 (33%) were penicillin-resistant. Of the
      75 Haemophilus influenzae pretreatment isolates, 42 (56%) produced beta-lactamase
      as did 4 (27%) of the 15 Moraxella catarrhalis strains. A satisfactory clinical
      response by pathogen was found in 75% (70 of 93) with S. pneumoniae, 75% (56 of
      75) with H. influenzae and 93% (13 of 14) with M. catarrhalis; the response with
      single pathogen infections was higher than those with multiple pathogens (118 of
      150 (78%) and 17 of 29 (59%), respectively; P = 0.03). The response for patients
      with isolates of S. pneumoniae that were penicillin-susceptible, -intermediate or
      -resistant were 39 of 50 (78%), 11 of 12 (92%) and 21 of 31 (68%), respectively.
      Older children had a satisfactory clinical outcome more frequently than younger
      children (P < 0.001), and the response to therapy varied for persistent,
      recurrent and recently untreated AOM (P < 0.01). CONCLUSION: Persistent and
      recurrent AOM involves the same pathogens as recently untreated AOM but bacteria
      with reduced antibiotic susceptibility may be more frequently present. This
      noncomparative study suggests that cefprozil 30 mg/kg/day given in two divided
      doses for 10 days may be effective in the treatment of children with persistent
      and recurrent AOM.

PMID- 9154540
TI  - Treatment of respiratory syncytial virus bronchiolitis: 1995 poll of members of
      the European Society for Paediatric Infectious Diseases.
AB  - BACKGROUND: Among the lower respiratory tract infections during infancy requiring
      hospitalization, respiratory syncytial virus (RSV) bronchiolitis is the most
      frequent disease entity. Nevertheless treatment remains controversial. METHODS: A
      poll among the European Society for Paediatric Infectious Diseases (ESPID)
      members was conducted to determine the respective local and national treatment
      policies of RSV bronchiolitis. RESULTS: The questionnaire was returned by 88
      centers represented in ESPID (response rate 64%). Ribavirin was used occasionally
      for high risk patients in 34 centers although 16 hospitals follow the guidelines
      of the Red Book Committee of the American Academy of Pediatrics. There were no
      centers using ribavirin for all patients. Bronchodilator treatment was used
      universally in various combinations for all patients in 54 centers and for all
      high risk patients in 15. Corticosteroids were used by > 80% of ESPID colleagues
      in various combinations of administration routes. CONCLUSION: The lack of
      effective treatment for RSV bronchiolitis and the controversy in the literature
      concerning antiviral, bronchodilator and antiinflammatory therapy leads to
      inconsistent treatment strategies.

PMID- 9154541
TI  - Extraintestinal salmonellosis in a children's hospital.
AB  - BACKGROUND: An increase in the number of patients presenting with extraintestinal
      salmonellosis has occurred at our institution. The purpose of this study was to
      review the extraintestinal salmonellosis cases in our institution and to
      investigate the possible reasons for this increase. METHODS: A retrospective
      review of patients from 1985 through 1996 was carried out to identify patients
      with extraintestinal infections with Salmonella. Demographic data were gathered
      and statistical evaluations comparing differences among groups (1985 to 1989,
      1989 to 1992, 1993 to 1996) was done using the G statistic, adjusted (maximum
      likelihood) chi square or the Fisher's exact test. RESULTS: Thirty-nine patients
      were identified with extraintestinal salmonellosis and although the number of
      cases had increased from 8 in 1985 to 1988 to 18 in 1989 to 1992 and 13 from 1993
      to 1996, the percentage of cases that were extraintestinal were similar (3.3%,
      6%, 4.9%; P > 0.1). Seventy-two percent of patients had underlying risk factors
      with the most common being age < 3 months (44%), sickle cell anemia (13%) and
      gastrointestinal surgery (10%). Fever and diarrhea were more common presenting
      symptoms in patients < 3 months of age than in older patients (P < 0.05).
      Salmonella typhimurium and Salmonella heidelberg were the most common serotypes
      isolated and an increasing trend of ampicillin resistance was noted from 0% in
      1985 to 1988 to 39% from 1989 to 1992 and 23% from 1993 to 1996. CONCLUSIONS: The
      reasons for an increasing trend in extraintestinal cases of human salmonellosis
      at our institution were not identified. This illness continues to occur in
      infants and children with well-recognized risk factors.

PMID- 9154542
TI  - Epidemiology of vancomycin usage at a children's hospital, 1993 through 1995.
AB  - OBJECTIVE: To describe the epidemiology of vancomycin usage at a children's
      hospital. METHODS: A cohort study of patients at Egleston Children's Hospital who
      were charged for the receipt of vancomycin from October, 1992, through October,
      1995, was performed. Data were obtained from pharmacy charge records in the
      hospital's medical records information system. RESULTS: During the study period
      there were 3589 patient hospitalizations in which vancomycin was used. Patients
      receiving vancomycin were predominantly male (56.6%) and white (62.4%), ranged in
      age from 0 to 31 (median, 3.8) years and had an average length of stay of 6.0
      days. The total number of vancomycin doses was 105,704; the median number of
      vancomycin doses during each patient hospitalization was 11.0 (range, 1 to 1215).
      The total charge for vancomycin used was $2,009,746; the median charge for
      vancomycin per patient was $297.50 (range, $11 to 19,864). The majority (75.7%)
      of vancomycin doses were given on the hematology (27.6%), neurosurgery (17.9%),
      cardiothoracic surgery (13.4%), neonatology (9.7%) or general pediatrics (7.1%)
      services. Overall surgery service patients were significantly more likely to
      receive vancomycin than were medicine service patients (1267 doses/6221
      admissions vs. 1954/19,446; relative risk, 2.03; P < 0.001). During the study
      period the number of vancomycin doses decreased significantly (P < 0.001).
      CONCLUSIONS: This study shows the value of evaluating antimicrobial use through a
      pharmacy database. Although vancomycin use decreased during the study period,
      large amounts of vancomycin are still being prescribed primarily on subspecialty
      service patients. Interventions to reduce vancomycin use should focus on these
      groups.

PMID- 9154543
TI  - Clinical signs of acute lower respiratory tract infections in malnourished
      infants and children.
AB  - OBJECTIVES: To determine the reliability of respiratory rate and subcostal
      retractions in diagnosing acute lower respiratory infection (ALRI) in
      undernourished children. METHODS: Three hundred twelve children with ALRI and 446
      with upper respiratory infection were classified according to weight and height
      as normal, stunted, wasted or stunted and wasted and also as normal, underweight
      or marasmus. The sensitivity and specificity of tachypnea, subcostal retractions
      and the presence of either sign in identifying children with a clinical diagnosis
      of ALRI or radiologic pneumonia in each of the nutritional categories were
      determined and compared. RESULTS: Among children with ALRI the mean respiratory
      rate in those with normal nutrition (61.5 +/- 16.1, n = 160) was not
      significantly different from those who were stunted (57.5 +/- 16.5, n = 59),
      wasted (61.3 +/- 14, n = 66) or stunted and wasted (55.4 +/- 12.8, n = 27) (P >
      0.05) or from those classified as underweight (60 +/- 15.9, n = 150) or marasmus
      (62.5 +/- 14.5, n = 27) (P > 0.4). The sensitivity and specificity of tachypnea,
      subcostal retraction or the presence of either sign in detecting ALRI was also
      not statistically significantly different among the children in the different
      nutritional categories (P > 0.05). The sensitivity of tachypnea or subcostal
      retraction in identifying children with radiologic pneumonia was also not
      significantly different among children in the different nutritional categories;
      the sensitivity of either sign was higher in under-weight children than in
      children with normal nutrition (P = 0.028). CONCLUSIONS: The data suggest that
      the current WHO algorithm is suitable for diagnosis of ALRI in undernourished
      children.

PMID- 9154544
TI  - Success of a scabies control program in an Australian aboriginal community.
AB  - OBJECTIVE: To adapt, implement and evaluate a model of scabies control in an
      Australian Aboriginal community. METHODS: After initially examining the
      population, we offered all residents treatment with 5% permethrin cream. Visits
      were made during the ensuing 25 months to rescreen and to treat new-cases of
      scabies and contacts. RESULTS: The prevalence of scabies was reduced from 28.8%
      before the program to < 10% during the entire period (from 32.3% to < 10% in
      children) (P < 0.01 for each visit). The initial prevalence of pyoderma in
      children was 69.4%, which was reduced and maintained at approximately one-half
      that rate during the last 16 months (P < 0.004 for the last 4 visits). Residual
      pyoderma in children was significantly less severe and no longer scabies-related.
      CONCLUSIONS: This simplified model of scabies control had a substantial effect on
      scabies prevalence and on pyoderma prevalence and severity which was sustained
      for > 2 years. It could prove useful for other communities with high rates of
      scabies and pyoderma.

PMID- 9154545
TI  - Risk of hospitalization because of aseptic meningitis after measles-mumps-rubella
      vaccination in one- to two-year-old children: an analysis of the Vaccine Safety
      Datalink (VSD) Project.
AB  - OBJECTIVE: To assess the level of increased risk, if any, of hospitalizations for
      aseptic meningitis after Jeryl-Lynn mumps strain measles-mumps-rubella (MMR)
      vaccine in the Vaccine Safety Datalink population. STUDY DESIGN: A possible
      increased risk of aseptic meningitis 8 to 14 days after receipt of MMR was
      observed in a preliminary screening analysis of automated data from the Vaccine
      Safety Datalink (VSD) project Year 2 analysis. To further evaluate this
      association a retrospective 10-year matched case-control study was undertaken in
      the four health maintenance organizations (HMOs) in the VSD project. Cases
      ascertained from a broad scan of the automated data were validated against a
      standard case definition. Two controls matched on age, sex, HMO and HMO
      membership were assigned per case. RESULTS: The VSD project involves the
      cooperative collection of automated vaccination and medical outcome data from
      four large HMOs that currently have 500,000 children younger than 7 years of age
      under surveillance. Review of automated screening results from the first 2 years
      of data revealed a possible increased risk of aseptic meningitis 0 to 14 days
      after MMR with a relative risk of 3.61 (95% confidence interval, 1.0 to 13.1)
      although the total number of cases was small. Although the automated data had
      suggested a possible association of aseptic meningitis with MMR containing the
      Jeryl-Lynn strain of mumps, review of validated hospitalized cases during the
      observation period did not reveal evidence of an increased risk of aseptic
      meningitis after MMR containing the Jeryl-Lynn strain of mumps (odds ratio < 1.0
      for all analyses). CONCLUSION: Although it is recognized that hospitalized cases
      represent a minority of the total cases of aseptic meningitis, it is reassuring
      that in this evaluation no increased risk of aseptic meningitis after MMR vaccine
      was found.

PMID- 9154546
TI  - Association of torovirus with acute and persistent diarrhea in children.
AB  - OBJECTIVE: To study the etiologic role of toroviruses as a cause of
      gastroenteritis in humans. METHODS: The design was a case-control study. We
      compared the rate of torovirus detection in fecal specimens from a selection of
      children with acute or persistent diarrhea and controls without diarrhea from a
      study of childhood diarrhea in an urban Brazilian slum. Stool samples were coded
      and tested in a blinded fashion for the presence of torovirus antigen by enzyme
      linked immunosorbent assay, other enteropathogens, toxins and fecal leukocytes.
      RESULTS: Thirty-three children with acute diarrhea, 41 children with persistent
      diarrhea and 17 controls were enlisted in the study. Torovirus antigen was
      detected in 9 (27%) samples from children with acute diarrhea, 11 (27%) samples
      from children with persistent diarrhea and none of the samples from controls (P <
      0.05). In addition the presence of enteroaggregative E. coli was associated with
      persistent diarrhea and the presence of Cryptosporidium oocysts was common
      although not significant (P = 0.08); torovirus and Cryptosporidium occurred in
      different subsets of samples, whereas torovirus and enteroaggregative Escherichia
      coli were commonly found in combination. CONCLUSIONS: These data indicate that
      toroviruses, alone or in combination with enteroaggregative E. coli, may play a
      pathogenic role in acute and possibly persistent diarrhea. Further studies are
      warranted to determine the etiologic role of toroviruses in gastroenteritis.

PMID- 9154547
TI  - The acellular pertussis vaccine trials: an interpretation.

PMID- 9154548
TI  - Terms of mutualism.

PMID- 9154549
TI  - Prevalence of antimicrobial resistance among pneumococcal isolates from children
      with otitis media in southern Israel.

PMID- 9154550
TI  - Penetration of dapsone into lung of human immunodeficiency virus-infected
      children.

PMID- 9154551
TI  - Severe neonatal echovirus 20 infection characterized by hepatic failure.

PMID- 9154552
TI  - Clostridium tertium meningitis as the presenting sign of a meningocele in a
      twelve-year-old child.

PMID- 9154553
TI  - Chronic Candida albicans otitis media in children with immunodeficiency.

PMID- 9154554
TI  - Infections after shark attacks in Australia.

PMID- 9154555
TI  - Syndrome of inappropriate secretion of antidiuretic hormone associated with
      exanthem subitum.

PMID- 9154556
TI  - Natural recovery from acute hepatitis C virus infection by agammaglobulinemic
      twin children.

PMID- 9154557
TI  - Chronic abdominal pain and Helicobacter pylori.

PMID- 9154558
TI  - Pneumococcal vaccination of children with recurrent sinusitis.

PMID- 9154559
TI  - Rarity of cryptococcal infection in children.

PMID- 9154561
TI  - Community-acquired bacteremia in Zimbabwe and the global cost of contaminated
      blood cultures.

PMID- 9154560
TI  - Streptococcus pneumoniae, otitis media and antimicrobial breakpoints.

PMID- 9154562
TI  - Influenza immunization for children with bronchopulmonary dysplasia in Poland.

PMID- 9154563
TI  - Haemophilus influenzae type b secondary infection of subdural hematomas.

PMID- 9154564
TI  - "Hamburger sign" in aseptic meningitis.

PMID- 9154565
TI  - Timing therapy for meningococcal infection.

PMID- 9154566
TI  - Efficacy of three-day azithromycin vs. ten-day penicillin V in the treatment of
      streptococcal pharyngitis.

PMID- 9154567
TI  - Clinicopathologic and neurochemical correlates of major depression and psychosis
      in primary dementia.

PMID- 9154568
TI  - Neurochemistry and neurotransmitters.

PMID- 9154569
TI  - Neuropathology of psychotic symptoms in Alzheimer's disease.

PMID- 9154570
TI  - Neuroimaging and the origin of psychiatric symptoms in dementia.

PMID- 9154571
TI  - Circadian rhythm-related behavioral disturbances and structural hypothalamic
      changes in Alzheimer's disease.

PMID- 9154572
TI  - Self-psychology: its application to understanding patients with Alzheimer's
      disease.

PMID- 9154573
TI  - Environmental and social aspects of behavioral disturbances in dementia.

PMID- 9154574
TI  - Behavioral disturbances of dementia and caregiver issues.

PMID- 9154575
TI  - Diagnostic classification of neuropsychiatric signs and symptoms in patients with
      dementia.

PMID- 9154576
TI  - Behavioral disturbances of dementia: practical and conceptual issues.

PMID- 9154577
TI  - Behavioral disturbances of dementia in DSM-IV and ICD-10: fact or fiction?

PMID- 9154578
TI  - Theories behind existing scales for rating behavior in dementia.

PMID- 9154579
TI  - Behavioral pathology in Alzheimer's disease (BEHAVE-AD) rating scale.

PMID- 9154580
TI  - Conceptualization of agitation: results based on the Cohen-Mansfield Agitation
      Inventory and the Agitation Behavior Mapping Instrument.

PMID- 9154581
TI  - CERAD behavior rating scale for dementia.

PMID- 9154582
TI  - Caretaker Obstreperous Behavior Rating Scale.

PMID- 9154584
TI  - Dementia Mood Assessment Scale.

PMID- 9154583
TI  - Dementia Behavior Disturbance Scale.

PMID- 9154585
TI  - Dysfunctional Behavior Rating Instrument.

PMID- 9154586
TI  - Direct observation of behavioral disturbances of dementia and their environmental
      context.

PMID- 9154587
TI  - Selecting outcome measures for clinical trials of behavioral disturbances of
      dementia.

PMID- 9154588
TI  - Antipsychotic treatment in outpatients with dementia.

PMID- 9154589
TI  - Behavioral symptoms in dementia: community-based research.

PMID- 9154590
TI  - Nursing home research from industry's perspective.

PMID- 9154591
TI  - Nursing home research from investigators' perspective.

PMID- 9154592
TI  - Meta-analysis of controlled pharmacologic trials.

PMID- 9154593
TI  - Delusions.

PMID- 9154594
TI  - Hallucinations.

PMID- 9154595
TI  - Misidentifications.

PMID- 9154596
TI  - Agitation, wandering, pacing, restlessness, and repetitive mannerisms.

PMID- 9154597
TI  - Disinhibition, apathy, indifference, fatigability, complaining, and negativism.

PMID- 9154598
TI  - Emotional lability, intrusiveness, and catastrophic reactions.

PMID- 9154599
TI  - Depression, anxiety, and sleep disturbances.

PMID- 9154600
TI  - Falling, hoarding and hiding, eating disturbances, and sexual disinhibition.

PMID- 9154601
TI  - Differentiating behavioral disturbances of dementia from symptoms of delirium.

PMID- 9154602
TI  - Differentiating behavioral disturbances of dementia from drug side effects.

PMID- 9154603
TI  - Behavioral disturbances of dementia in the nursing home.

PMID- 9154604
TI  - Behavioral disturbances of dementia in ambulatory care settings.

PMID- 9154605
TI  - Vascular dementia and Alzheimer's disease: should we be studying both within the
      same study?

PMID- 9154607
TI  - Caregivers and behavioral disturbances: effects and interventions.

PMID- 9154606
TI  - Perspectives of a family caregiver.

PMID- 9154608
TI  - Perspective of an institution-based research nurse.

PMID- 9154609
TI  - Perspective of a clinical trials research nurse.

PMID- 9154610
TI  - Behavioral and psychological signs and symptoms of dementia: implications for
      research and treatment. Cross-cultural perspectives. Argentina.

PMID- 9154611
TI  - Behavioral and psychological signs and symptoms of dementia: implications for
      research and treatment. Cross-cultural perspectives: India.

PMID- 9154613
TI  - Cross-cultural perspectives: agitation in demented patients in the United States.

PMID- 9154612
TI  - Cross-cultural perspectives: Caribbean, Native American, and Yoruba.

PMID- 9154614
TI  - Future research directions.

PMID- 9154615
TI  - Behavioral and psychological signs and symptoms of dementia: a consensus
      statement on current knowledge and implications for research and treatment.

PMID- 9154616
TI  - The effect of strain of broiler on physiological parameters associated with the
      ascites syndrome.
AB  - Differences among eight commercial broiler strains in factors indicating
      susceptibility to ascites were investigated. Chicks from eight crosses were
      obtained from two hatcheries (one was obtained from both hatcheries to give a
      total of nine) and raised to 6 wk of age on commercially prepared rations
      containing 3,300 kcal/kg energy with 24% protein to 3 wk of age and 20% protein
      from 3 to 6 wk. Each cross was represented by four pens of 90 broilers each. At
      21 and 42 d, groups of 20 birds per pen were weighed and feed consumption was
      measured in order to calculate the feed conversion ratio. At 21 and 42 d, a blood
      sample was taken from two birds per pen to determine the hematocrit value. These
      birds were killed and dissected to determine heart, liver, lung, and spleen
      weights. Lung volume was determined by water displacement. Significant
      differences were observed between crosses for all of the measures with the
      exception of feed conversion ratio and mortality. These differences were most
      prominent for hematocrit value, which is an initial adaptation to anoxia,
      suggesting that broiler lines could be chosen that resist anoxic environmental
      conditions.

PMID- 9154617
TI  - Beak trimming of turkeys. 2. Effects of arc beak trimming on weight gain, feed
      intake, feed wastage, and feed conversion.
AB  - An experiment was conducted to study the effects of arc beak trimming on feed
      consumption, weight gain, and feed wastage in males and females from two large
      bodied strains and one medium-bodied strain of turkeys. Birds were placed in wire
      floored battery cages from 3 to 8 wk of age and feed intake, weight gains, and
      feed spilled into dropping pans were recorded for each of the 5 wk of each trial.
      Feed conversion was calculated as feed consumed divided by weight gained. Sex by
      beak trimming interactions were not found. Beak trimming reduced feed wastage of
      the two large-bodied strains, but did not affected feed wastage of the medium
      bodied strain, which did not consume as much feed as the large-bodied strains.
      The results of this study support the hypothesis that beak trimming reduces feed
      wastage of large-bodied turkeys.

PMID- 9154618
TI  - Localization and enumeration of T and B lymphocytes in the reproductive tract of
      laying hens.
AB  - Distribution and the relative frequencies of subclasses of T and B lymphocytes in
      the 360-d-old, healthy laying hens were studied. Avidin-Biotin-Peroxidase Complex
      (ABC) method was used to detect T cells, whereas Indirect Immunofluorescent
      Technique (IFT) was applied to detect B cells. Both T and B cells were scattered
      throughout the ovaries and oviducts. Small lymphoid nodules were found in the
      upper regions of the oviducts. More T lymphocytes were found in the vagina,
      ovary, and infundibulum than in the other portions examined, whereas B
      lymphocytes were mainly found in magnum, uterus, and isthmus. The IgG-containing
      (B) cells were not found in the ovary. The CD8+ cells were found more close to
      the lining epithelium or in between epithelial cells, whereas CD4+ cells were
      found mainly in the lamina propria. The behavior of these cells in certain
      infectious diseases in which the ovaries and oviducts are major predilection
      sites would be very important in assessing or determining local immune responses.

PMID- 9154619
TI  - Resistance, susceptibility, and immunity to Eimeria tenella in major
      histocompatibility (B) complex congenic lines.
AB  - The major histocompatibility (B) complex influence on resistance, susceptibility,
      and immunity to Eimeria tenella was examined in UCD B complex congenic chicken
      lines. In Experiment 1, 6-wk-old chicks from 12 UCD congenic lines were weighed
      and assigned to either challenge or control groups. The challenge group received
      a dose of 10,000 E. tenella oocysts. Response to challenge was evaluated by body
      weight gain and cecal lesion scores. Cecal lesion scores in B3B3 chickens were
      significantly lower than those of all other genotypes. Genotype B2B2 had the
      highest lesion scores, which were significantly different from the lesion scores
      calculated for B3B3, B18B18, and B21B21 chickens but were not significantly
      different from B14B14, B15B15, B17B17, B19B19, B24B24, BCBC, BJBJ, and BQBQ
      genotypes. The B21B21 chickens had significantly lower lesion scores than B2B2,
      B14B14, and BCBC chickens. No other significant lesion score differences were
      found among the remaining lines. The highest weight gain found in B19B19 chickens
      was significantly different from that of B3B3, B14B14, B15B15, B17B17, B18B18,
      B24B24, and BCBC chickens. The B15B15 chickens had the lowest weight gain, which
      was significantly different from that of B2B2, B19B19, B21B21, B24B24, BJBJ, and
      BQBQ chickens. Experiment 2 tested the immune response to E. tenella after low
      dose oocyst immunization. Chicks from 10 UCD 003 congenic lines were divided into
      three groups: control, challenge, and immune. At 5 wk of age, the immune group
      was immunized with 500 E. tenella oocysts for 5 consecutive d. Fourteen days
      after the last immunization all chicks were weighed, and 10,000 E. tenella
      oocysts were administered to the challenge and immune groups. Significant lesion
      score differences existed among all three treatments: control (0), immune (2.14
      +/- 0.1); challenge (3.13 +/- 0.1). Among immune birds, B3B3 and BQBQ chickens
      had significantly lower lesion scores than B19B19, B24B24, B14B14, and B2B2
      chickens. Neither B19B19 nor B24B24 chickens were well-protected, as indicated by
      their higher lesion scores. No significant differences in weight gain were found
      in immune birds. The B complex affected resistance and susceptibility as well as
      the immune response to E. tenella. Cecal lesion scores following challenge in
      naive birds or after immunization were influenced by the B complex, whereas
      weight gain was affected in naive birds only. These effects may be manifested
      through differences in immune competence at the time of challenge or
      immunization, the amount of parasite antigen production, or the threshold doses
      for effective immunization.

PMID- 9154620
TI  - The influence of environmental temperature on in vivo limestone solubilization,
      feed passage rate, and gastrointestinal pH in laying hens.
AB  - Several studies were conducted to determine whether suppression of in vivo
      limestone solubilization was partially responsible for the reduction of shell
      quality under conditions of high environmental temperatures. In Experiment 1,
      excreta from hyperthermic and thermoneutral hens fed three levels of Ca (3.5,
      4.3, and 5.2%) at two cycling environmental temperatures (averaging 28.3 and 26.1
      C) were analyzed for percentage in vivo limestone solubilization. Hens in
      Experiment 2 received diets containing 3.9% Ca at 32.8 and 18.3 C. Rate of feed
      passage and gastrointestinal pH were also measured in Experiment 2. Experiment 3
      evaluated the influence of temperature (22.2 and 30.0 C) and feed consumption on
      percentage limestone solubilization when Ca intake was held constant. In vivo
      limestone solubilization was influenced by Ca level in Experiment 1, but not by
      temperature. Hyperthermic hens solubilized a higher percentage of limestone than
      thermoneutral hens in Experiment 2, but it was concluded that this was due to a
      difference in Ca consumption and not due to temperature directly. When Ca intake
      was held constant in Experiment 3, there was no difference in limestone
      solubilization at the temperatures tested. Rate of feed passage was 16.6% slower
      in the hyperthermic hens. Crop, proventriculus, and upper small intestine pH were
      similar at each temperature, but gizzard pH was significantly lower in the
      hyperthermic hens. It was concluded that the high environmental temperatures used
      in the present studies did not suppress in vivo limestone solubilization.

PMID- 9154622
TI  - Effects of dietary threonine in starting, growing, and finishing turkey toms.
AB  - The present study investigates the threonine requirements of British United
      Turkey (BUT) Big 6 turkey toms from 0 to 4, 8 to 12, and 16 to 20 wk of age.
      Growth, feed conversion, and carcass quality responses to increasing dietary
      threonine levels were measured. From 0 to 4 wk of age (57 g to 1.1 kg live
      weight), a dietary threonine level of about 0.95% (3.3 g/Mcal ME) was found to be
      adequate to obtain optimum growth and feed conversion. From 8 to 12 wk of age
      (4.0 to 8.6 kg live weight), there was no significant response to dietary
      threonine beyond the basal level of 0.69% (2.2 g/ Mcal ME). From 16 to 20 wk of
      age (13.1 to 18.7 kg live weight), a threonine level of about 0.58% (1.8 g/Mcal
      ME) appeared to be adequate to obtain optimum growth. For optimum breast meat
      deposition, a higher level in the range of 0.64% (2.0 g/Mcal ME) dietary
      threonine was required. The present findings may point to the importance of
      threonine as potentially third limiting amino acid after methionine and lysine in
      cereal-based turkey diets.

PMID- 9154621
TI  - Dietary safflower phospholipid reduces liver lipids in laying hens.
AB  - This experiment was conducted to determine the effects of dietary safflower
      phospholipids (crude safflower phospholipid and purified safflower phospholipid)
      on performance and lipid metabolism of laying hens. Sixty-week-old Single Comb
      White Leghorn laying hens were divided into four groups of seven birds each, and
      were given one of four experimental diets containing 5% beef tallow (served as a
      control, tallow), a mixture of safflower oil and palm oil (SP-oil), crude
      safflower phospholipid (Saf-PLcrude), or purified safflower phospholipid (Saf-PL)
      for 7 wk. Egg production ratio and daily egg mass were significantly higher in
      hens fed Saf-PLcrude diets than in hens of the other diet groups. There were no
      significant differences in egg weight among groups. Liver cholesterol and
      triglyceride contents were significantly decreased in all treated groups as
      compared with the control. The activity of hepatic 3-hydroxy-3 methylglutaryl
      coenzyme A reductase was the highest in hens fed the Saf-PLcrude diet. Serum
      esterified cholesterol concentration was decreased by feeding of SP-oil, Saf
      PLcrude, or Saf-PL diets. Serum lecithin-cholesterol acyltransferase activity was
      highest in hens fed the tallow diet. Excreta neutral steroid excretion was
      significantly increased in the Saf-PLcrude or Saf-PL diet groups, although acidic
      steroid excretion was not affected by dietary treatments. Total cholesterol,
      triglyceride, and phospholipid contents in egg yolks were not different for any
      dietary treatments. The fatty acid compositions of egg yolks from hens fed Saf
      PLcrude diets were not different with those fed the SP-oil diet, although eggs of
      hens fed the Saf-PL diet showed lower total polyunsaturated fatty acids. These
      results suggest that dietary safflower phospholipids may be a valuable ingredient
      to layers for reducing liver triglycerides and serum cholesterol without any
      adverse effects.

PMID- 9154624
TI  - Evaluation of National Research Council amino acid recommendations for large
      white turkeys.
AB  - Two trials of identical experimental design were conducted to evaluate the NRC
      (1994) amino acid requirements for growing turkeys. Diets were formulated for 4
      wk age intervals using intact ingredients and amino acid supplements to provide
      85, 90, 95, 100, 105, 110, 115, and 120% of the suggested requirements.
      Formulation was done in a manner to minimize excess levels of as many essential
      amino acids as possible. Day-old male poults of a commercial Large White strain
      were grown to 20 wk on the test diets with body weight and feed conversion
      determined at intervals throughout the test; representative samples of birds were
      processed to determine carcass composition and parts yield. Results suggested
      that diets formulated to provide 105% of the suggested NRC requirements were
      needed to provide maximum body weight gain, feed conversion, and breast meat
      yield. Ambient temperatures in the present study frequently exceeded 27 C and may
      have contributed to the need for somewhat greater amino acid needs than the
      present NRC (1994) suggestions.

PMID- 9154623
TI  - Effects of dietary magnesium excess in White Leghorn hens.
AB  - The effects of excess dietary magnesium on White Leghorn laying hens were
      investigated in two experiments and a third experiment looked at the effect of
      dietary phosphorus on excess magnesium in the diet. In Experiment 1, magnesium
      levels of 0.15, 0.8, and 1.2% were fed in a diet containing 2.5% calcium to hens
      30 wk of age for 5 wk. A control diet with 3.5% calcium and 0.15% magnesium was
      also fed. In Experiment 2, hens 65 wk of age fed 3.5% calcium were fed dietary
      magnesium levels of 0.15, 0.36, 0.53, 0.76, and 0.91% for 4 wk. In these two
      experiments, excess magnesium reduced egg production, decreased feed consumption,
      decreased body weight, decreased percentage eggshell, reduced plasma calcium, and
      increased plasma magnesium and tibia magnesium but changes seen in tibia weight,
      percentage ash, and tibia calcium and phosphorus were variable. More changes from
      feeding excess magnesium were seen in the young, high producing hens in
      Experiment 1. In Experiment 3, hens 50 wk of age were fed a marginal calcium
      level (2.5%) with an excess of magnesium (0.8%) and a control level of available
      phosphorus (0.45%) and this was compared to a low (0.25%) and a high level (0.9%)
      of available phosphorus for a 4-wk experimental period. At the end of the
      experimental period, hens fed low phosphorus had lower egg production and lower
      feed consumption than the hens fed higher levels of phosphorus. Body weight was
      lower in the hens fed the two lower levels of phosphorus. Percentage eggshell was
      lower than the controls when fed low phosphorus and higher when fed high
      phosphorus. These results suggest that high phosphorus diets are better than low
      phosphorus diets when excess magnesium is fed to laying hens. Further study is
      needed to investigate the role of phosphorus when excess magnesium is fed.

PMID- 9154625
TI  - Artificial neural network prediction of amino acid levels in feed ingredients.
AB  - Artificial Neural Networks (ANN), which are biologically inspired tools, serve as
      an alternative to regression analysis for complex data. Based on CP or proximate
      analysis (PA) of ingredients, two types of ANN and linear regression (LR) were
      evaluated for predicting amino acid levels in corn, wheat, soybean meal, meat and
      bone meal, and fish meal. The two ANN were a three layer Backpropagation network
      (BP3), and a General Regression Neural Network (GRNN). Methionine, TSAA, Lys,
      Thr, Tyr, Trp, and Arg were evaluated and R2 values calculated for each
      prediction method. Artificial neural network training was completed with
      NeuroShell 2 using Calibration to prevent overtraining. Ninety percent of the
      data were used as the input for the LR and the two ANN. The remaining 10%
      (randomly extracted data) were used to calibrate the performance of the ANN. As
      compared to LR, the R2 values were largest when PA input and GRNN were used. The
      BP3 did not consistently improve the R2 values for either CP or PA inputs as
      compared to LR. Each neural net can be incorporated into a computer or
      spreadsheet program.

PMID- 9154626
TI  - Feeding and excreta collection techniques in metabolizable energy assays for
      ducks.
AB  - Feeding and excreta collection techniques, lasting 102 h, for the determination
      of ME in feed ingredients for ducks are described. Eight and 32 h after feed
      withdrawal, all ducks received 30 g of dextrose in 100 g of water by orogastric
      administration. By orogastric administration, ducks received 30 g of test
      ingredients or dextrose (for ducks used in estimation of endogenous losses of
      energy and nitrogen) in 100 g of water at 48 and 54 h after feed withdrawal. The
      collection of excreta involved suturing a threaded plastic retainer ring to the
      vent and screwing a Whirl-Pak plastic bag, mounted on the top portion of a
      Playtex baby nurser set plastic bottle cut off 3 cm below the threads, to the
      retainer ring. Excreta were collected by replacing the Whirl-Pak bags at 54, 60,
      72, 84, 96, and 102 h after feed withdrawal. In each of two experiments, ducks
      with an average weight of 3.7 kg were assigned to treatments. In Experiment 1,
      four ducks were assigned to each of three test ingredients (corn, dehulled oats,
      and wheat) and four ducks were assigned to be deprived of feed for estimation of
      endogenous losses of nitrogen and energy. In Experiment 2, six ducks were
      assigned to each of two test ingredients (corn and sorghum) and six ducks were
      assigned to be deprived of feed. Ducks lost an average of 537 g (Experiment 1)
      and 462 g (Experiment 2) during the 102-h experimental period and all the lost
      weight was regained within 7 d of return to full feed. Losses of nitrogen
      (milligrams per duck per 54 h) were 292 (Experiment 1) and 461 (Experiment 2) and
      energy (kilocalories per duck per 54 h) were 12.12 and 22.26 in feed-deprived
      group. The determined AMEn and TMEn for corn were 3.245 and 3.407, and 3.210 and
      3.517 kcal/g for Experiments 1 and 2, respectively. For dehulled oats, wheat, and
      sorghum, the determined AMEn and TMEn were 3.464 and 3.625, 3.150 and 3.312, and
      3.363 and 3.670 kcal/g, respectively.

PMID- 9154627
TI  - A deleted retroviral insertion at the ev21-K complex locus in Indonesian
      chickens.
AB  - Very poor feather development has been observed in chickens of the Nunukan
      strain, originating from Indonesia. The wing of the newly hatched chick does not
      show any primary or covert feathers; this phenotype will be referred to as very
      late feathering (VLF). As adults, chickens are feathered but tail feathers are
      short and fragile. An experimental population was set up at the National
      Institute of Agronomic Research (INRA), Jouy-en-Josas, from one Nunukan male and
      four Nunukan females. Preliminary observations did not support the hypothesis of
      a sex-linked dominant mode of inheritance for the VLF phenotype. A restriction
      fragment length polymorphism (RFLP) study using five restriction enzymes and two
      probes, RAV-2 and endogenous virus (ev) ev21-int specific for the endogenous
      viral locus ALVE21, showed the presence of the expected 3' junction fragments for
      the ev21 occupied site but failed to reveal the expected 5' junction fragments
      for ev21 in Nunukan chickens. The unoccupied site corresponded to the ev21
      unoccupied repeat (UR) of type a (URa). A deletion in the 5' region of the
      provirus and of the insertion site was indicated by the RFLP analysis and
      confirmed by a PCR study. Primers were designed in order to amplify a 5' junction
      fragment specific to the modified ev21 found in the Nunukan chickens. The
      sequence of this amplified product showed that the deletion started 652 bp
      upstream of the insertion site of ev21 and ended within the pol gene of the viral
      genome. This deletion represents a new allele, OSD, at the ev21 insertion site
      (locus ALVE21), that appears insufficient to produce a complete virus. Current
      data do not show a clear causal relationship between OSD and the VLF phenotype.
      The presence of OSD may be required but is not in itself sufficient to obtain the
      VLF phenotype. The genetic relationships between OSD and the altered feathering
      phenotype of Nunukan chickens will be investigated further in families
      segregating for the VLF phenotype, using the locus-specific PCR test developed as
      part of this study.

PMID- 9154628
TI  - Comparative mapping of the chicken genome using the East Lansing reference
      population.
AB  - The annotation of known genes on linkage maps provides an informative framework
      for synteny mapping. In comparative gene mapping, conserved synteny is broadly
      defined as groups of two or more linked markers that are also linked in two or
      more species. Although many anonymous markers have been placed on the chicken
      genome map, locating known genes will augment the number of conserved syntenic
      groups and consolidate linkage groups. In this report, 21 additional genes have
      been assigned to linkage groups or chromosomes; five syntenic groups were
      identified. Ultimately, conserved syntenic groups may help to pinpoint important
      quantitative trait loci.

PMID- 9154629
TI  - Binding of spermatozoa to the perivitelline layer in the presence of a protease
      inhibitor.
AB  - The extracellular investment of oocytes in a number of species contains species
      specific receptors to which spermatozoa bind as a prelude to fertilization;
      however, little is known about the nature and distribution of sperm receptors in
      avian oocytes. In order to elucidate the early step of fertilization in birds, we
      observed the binding of spermatozoa to the perivitelline layer (PL) of quail ova.
      When the PL obtained from the largest follicles were incubated in vitro with
      spermatozoa, perforations were observed. The presence of trypsin inhibitors
      during incubation inhibited the sperm-induced perforations of the PL and binding
      of spermatozoa to the PL could be observed. The number of spermatozoa bound to
      the PL increased in the ovum from more mature follicles, and concentrated binding
      of spermatozoa to the PL overlying the germinal disc region was observed in the
      largest follicle. The number of spermatozoa bound to the PL overlying the
      germinal disc region decreased in the oviposited eggs. These results demonstrate
      that sperm receptors exist in the PL over the germinal disc in the mature
      follicle.

PMID- 9154630
TI  - Production of chicken chimeras from injection of frozen-thawed blastodermal
      cells.
AB  - To execute a strategy for reconstituting genetic resources from cryopreserved
      blastodermal cells, experiments were conducted to optimize conditions for
      producing chimeric chickens from frozen-thawed blastodermal cells. Stage X
      blastodermal cells were collected from Barred Plymouth Rock embryos and
      dispersed. Cells were resuspended in 10% dimethyl sulfoxide in Dulbecco's
      modified Eagle's medium (DMEM) containing 20% fetal bovine serum, and distributed
      into plastic ampules. Cell suspensions were seeded to induce ice formation at -7
      C, cooled from -7 to -35 C at 1 C/min and then ampules were plunged into liquid
      nitrogen. Thawing was done by plunging the ampules into warm water (37 C) for 3
      min. After centrifugation, the supernatant was replaced with DMEM, and dead or
      broken cells were removed by density gradient centrifugation. Approximately 500
      cells were injected into irradiated Stage X White Leghorn recipient embryos.
      Following incubation, several somatic chimeras were produced. The frequency of
      somatic chimerism when fresh (unfrozen) cells, or cells that were frozen and
      selected by density gradient centrifugation on Percoll or Nycoprep were injected
      into recipient embryos was 84, 79, and 85%, respectively. The percentage of donor
      derived pigmentation in the down of these chimeric chickens was 79, 50, and 58%,
      respectively. Germline chimerism was determined by mating the chimeras that
      survived to sexual maturity to Barred Plymouth Rocks. Nine of 16 birds (56.2%)
      injected with fresh cells, 2 of 26 birds (7.7%) injected with cells that were
      frozen and selected by density gradient centrifugation on a Percoll gradient, and
      3 of 26 birds (11.5%) injected with cells that were frozen and selected on a
      Nycoprep gradient showed germline transmission; the percentage of donor-derived
      progeny in these chimeras were 29.5, 5.2, and 6.8%, respectively. The Barred
      Plymouth Rock donor stock was "reconstituted" by inter se mating of germline male
      and female chimeras. These data demonstrate that the strategy described here for
      reconstituting genetic resources from cryopreserved blastodermal cells via
      chimeric intermediates can be performed successfully.

PMID- 9154631
TI  - Ahemeral lighting of turkey breeder hens. 1. Cycle length effects on egg
      production and egg characteristics.
AB  - A study was conducted to determine the effective range of light-dark cycle
      lengths for reproductive performance in turkey hens. The treatments consisted of
      seven different light-dark cycle lengths: 21, 23, 24, 26, 27, 28, and 30 h each
      with a 15-h photophase per cycle. Data were collected for BW, feed intake,
      livability, onset and rate of egg production, egg weight (EW), shell thickness,
      and weight of egg components. The results indicate that turkey hens can be
      induced to lay eggs with light-dark cycle lengths other than 24 h (ahemeral) with
      practical extremes being about 23 to 28 h. Egg production in the ahemeral
      treatments never significantly exceeded that occurring in the 24 h group and the
      percentage of floor eggs increased at cycle lengths greater than 26 h and at 21
      h. Cycle lengths of 21 and 30 h provided the most extreme deviations in the
      quantity and quality of eggs from those obtained on a 24 h cycle length. Shell
      thickness increased consistently as cycle lengths increased from 23 to 30 h. Egg
      weight increased in a curvilinear manner as cycle lengths increased or decreased
      from 24 h. This increase was associated with increases in shell, yolk, and
      albumen weight; however, the contribution by each was inconsistent, varying by
      cycle length as well as time on treatment. It may be concluded that an effective
      practical range of light-dark cycles for turkeys is 23 to 28 h and that 28 h is a
      reasonable limit to maximize EW and shell thickness while minimizing a reduction
      in egg production.

PMID- 9154632
TI  - Characteristics of the pectoralis superficialis and semimembranosus of broiler
      strain chickens, bantam chickens, and the reciprocal crosses.
AB  - At hatch, chicks from bantam sire x broiler dam (BaBr) matings were as heavy as
      those from broiler sire x broiler dam (BrBr) matings. Both were heavier than pure
      bantam chicks (BaBa) or chicks from broiler strain sires and bantam dams (BrBa),
      but weights of the latter two genotypes were identical. The Pectoralis
      superficialis and Semimembranosus of pure bantam chicks weighed less than those
      of pure broiler chicks throughout the studies. Muscle weights in the BaBr chicks
      were markedly heavier than those of genetically similar BrBa chicks at hatch.
      Genetic influences were quickly expressed and weights of muscles in these two
      groups had converged by 14 d of age. Myofiber cross-sectional areas at 1 d of age
      were not clearly associated with genotype or maternal environment, but clear
      patterns had begun to develop by 4 d of age. Myofiber area of both muscles was
      greater in BrBr than BaBa chicks by this age and after. Myofiber areas in the
      reciprocal crosses converged toward each other and away from the pure line
      chicks. By 11 d, the area of Pectoralis myofibers of BrBr chicks was greatest,
      those of the reciprocal crosses was intermediate and equal to each other, and
      that of BaBa chicks was least. A similar trend was apparent in Semimembranosus
      fibers by 11 d but the differences did not become significant until 21 d of age.
      Significant differences in myofiber number of the Semimembranosus were present
      (BrBr > BaBr > BrBa > BaBa). Thus, differences in muscle mass were the result of
      differences in both fiber number and fiber size.

PMID- 9154633
TI  - High temperature processing effects on the properties of fowl meat gels.
AB  - The effects of three moisture levels (0, 10, and 20% added water) and three
      processing temperatures (115.6, 121.1, and 126.7 C) on texture and collagen
      solubilization of fowl meat gels were examined. Meat gels were formulated from
      spent fowl breast meat that were cooked in water (71.1 C internal temperature)
      prior to heat processing. The water-cooked gels were heat processed at the three
      temperatures to an F0 value of 6.0 (Z value = 10 C). The addition of 20% water
      resulted in a reduction of the soluble collagen compared to the 10% water-added
      treatment. The lowest processing temperature increased the soluble collagen
      compared to the highest processing temperature. Shear stress and hardness
      decreased as the amount of added water was increased; and the lowest processing
      temperature resulted in the lowest hardness values. The increase in soluble
      collagen parallels the decrease in hardness in the samples processed at the
      lowest temperature. Because each sample was processed to equivalent F values, the
      lowest processing temperature had the longest exposure time (26 min at 115.6 C,
      12 min at 121.1 C, and 6 min at 126.7 C). The longer exposure to moist heat
      allowed for greater collagen solubilization and lower hardness values. The 0%
      added-water treatment had the highest yield from before and after heat
      processing. However the 10% water-added samples had the greatest overall water
      retention when each treatment was placed on an equal level of initial water
      content. Furthermore, the highest processing temperature (shortest processing
      time) resulted in the greatest yield and moisture retention compared to the other
      processing temperatures.

PMID- 9154634
TI  - The effect of evisceration on visible contamination and the microbiological
      profile of fresh broiler chicken carcasses using the Nu-Tech Evisceration System
      or the conventional Streamlined Inspection System.
AB  - Experiments were conducted to determine the effect of evisceration on visible
      contamination and the microbiological profile of fresh broiler chicken carcasses
      using the Nu-Tech System or the Streamlined Inspection System (SIS). Visible
      contamination was evaluated on the inside cavity and outside surface of 1,000 and
      7,825 carcasses from Plants A and B, respectively, during 5 d of processing. For
      the microbiological study, in five separate trials, 80 broiler carcasses were
      collected each day from two processing plants (A and B). Two groups of 20
      carcasses each were collected immediately prior to entering the Nu-Tech
      eviscerator, bagged separately, and 20 were labeled as NT1 and 20 as SIS1. The
      third group of 20 carcasses was collected immediately after the cropper on the Nu
      Tech line and labeled NT2. For the fourth group, 20 carcasses were aseptically
      transferred from the Nu-Tech line just prior to evisceration, placed on the SIS
      line prior to evisceration, allowed to be eviscerated by the SIS eviscerator,
      collected immediately after the cropper, and labeled SIS2. Whole carcass rinses
      were conducted and aerobic plate counts (APC), total coliform counts (TC), total
      Escherichia coli counts (TEC), aerobic mesophilic impedance detection times (DT),
      and coliform impedance detection times (CDT) were determined within 30 h of
      collection. The Nu-Tech System was superior to SIS with regard to visible carcass
      contamination. For Plant A, evisceration using the Nu-Tech System or SIS did not
      significantly affect APC, TC, or TEC; however, evisceration using the Nu-Tech
      System resulted in an increase in DT and CDT (indicating a reduction in
      bacteria); whereas evisceration using SIS resulted in no significant decrease in
      bacterial levels. For Plant B, evisceration using the Nu-Tech resulted in lower
      APC, TC, TEC, and higher DT and CDT (indicating a reduction in bacteria); whereas
      evisceration using SIS resulted in no significant decrease in bacterial levels.
      Evisceration using the Nu-Tech System was at least equal to or in some cases
      better than SIS with regard to APC, TC, TEC, DT, and CDT.

PMID- 9154635
TI  - Effect of muscle opposition during rigor on development of broiler breast meat
      tenderness.
AB  - Two experiments were conducted to determine the effect of mutual opposition of
      breast muscles during rigor development on ultimate tenderness of the cooked
      meat. In each experiment, 32 broilers were conventionally processed. Immediately
      after evisceration, the supracoracoideus tendon was cut at the humeral insertion
      on one wing (treatment) and the opposite wing was sham-operated with the tendon
      exposed but not cut (control). The tendon of insertion for the Pectoralis minor
      muscle was cut to prevent the opposition of breast muscles during rigor, while
      avoiding confounding effects caused by making cuts on the muscles, as would occur
      during typical deboning. Cutting the tendon significantly (P < 0.05) increased
      Warner-Bratzler shear values after cooking for both the Pectoralis major and P.
      minor. Deboning at 2 h post-mortem resulted in shear values for the P. major of
      7.22 kg for controls and 9.08 kg for treated carcasses; P. minor shear values
      were 2.98 kg for controls and 4.04 kg for treated carcasses. Deboning at 24 h
      post-mortem produced P. major shear values of 4.68 kg for controls and 5.68 kg
      for treated carcasses. On whole carcasses, breast muscle opposition during rigor
      contributes to the tenderness of the cooked meat.

PMID- 9154636
TI  - Development of further processed poultry products.

PMID- 9154637
TI  - Principles of receptor-based inhibition of erbB family receptor kinases:
      prospects for new therapies for human cancers.
AB  - The erbB family of receptor tyrosine kinases is composed of growth factor
      receptors that are overexpressed or mutated in a large variety of human cancers.
      The study of erbB-mediated signal transduction will lead to an understanding of
      the role played by this family of receptors in normal and transformed cells. In
      this article, we discuss the contemporary understanding of the structure and
      function of these receptors and how these features might be exploited in receptor
      based strategies of growth inhibition. The first part of our study details the
      structure of erbB receptors as it relates to the process of transformation of
      cells and the malignant phenotype in humans. In the second part, we discuss two
      rational approaches to therapy for cancers in which erbB receptors are
      overexpressed or mutated: first, the potential for antireceptor immunity and the
      evolution of small molecules for receptor-based immunotherapy; second, a strategy
      of ectodomain association that leads to the formation of defective kinase
      assemblies. These studies provide a basis for the application of receptor-based
      strategies of growth inhibition in erbB-expressing human cancers.

PMID- 9154638
TI  - Potentiation of beta-adrenergic signaling by gene transfer.
AB  - The beta-adrenergic signaling cascade is an important regulator of myocardial
      function. Numerous abnormalities occur in this pathway and are associated with
      impaired cardiac contractility in patients with congestive heart failure (CHF).
      These signaling defects include downregulation of beta-adrenergic receptors (beta
      ARs) and increased levels of beta-adrenergic receptor kinase (beta ARK), an
      enzyme that phosphorylates and uncouples only agonist-bound receptors. Our
      laboratory has been testing the hypothesis that reversal of these beta-adrenergic
      defects may be able to restore cardiac inotropy to normal in patients with
      depressed systolic function. Transgenic mice with cardiac overexpression of beta
      2ARs or an inhibitor of beta ARK have enhanced cardiac function as compared to
      wildtype littermates. Adenoviral vectors encoding the beta 2AR or beta ARK
      inhibitor potentiate beta AR signaling in cultured adult rabbit ventricular
      myocytes. However, a controversy has developed in the literature regarding
      whether increasing beta-adrenergic signaling would be beneficial or detrimental
      for patients with CHF. Those cautioning against this approach note that increased
      sympathetic activity is dangerous in CHF. Elevated catecholamine levels predict
      mortality and beta-agonists are not beneficial for survival, while recent studies
      suggest that beta-antagonists do improve outcome. Supporting these concerns is
      the demonstration that transgenic mice with cardiac overexpression of Gs alpha
      and enhanced myocardial responsiveness to isoproterenol develop myocardial
      fibrosis. This article summarizes this controversy; highlights important
      differences between overexpression of beta ARs or a beta ARK inhibitor,
      overexpression of Gs alpha, and administration of beta-agonists; and develops the
      hypothesis that these strategies may differ in their therapeutic efficacy in
      treating CHF.

PMID- 9154639
TI  - Heightened transmigrating activity of CD4-positive T cells through reconstituted
      basement membrane in patients with human T-lymphotropic virus type I-associated
      myelopathy.
AB  - We investigated the transmigrating activity of peripheral blood T cells of
      patients with human T-lymphotropic virus type I-associated myelopathy (HAM)
      through reconstituted basement membrane. The transmigrating activity of CD4+ T
      cells of HAM patients was increased significantly in comparison to that of anti
      HTLV-I-seropositive carriers and HTLV-I-seronegative controls. However, the
      migrating activity of CD8+ T cells was not significantly different in HAM
      patients and controls. The activity of aminopeptidase-N in peripheral blood T
      cells of HAM patients also was increased significantly, as compared to that of
      controls. In addition, HTLV-I proviral load in transmigrating CD4+ T cells of HAM
      patients was increased significantly (two- to eight-fold), compared to that in
      nontransmigrating CD4+ cells. By contrast, no significant difference in HTLV-I
      proviral load was found between transmigrating and nontransmigrating CD4+ cells
      of HTLV-I-seropositive carriers, although copy numbers of HTLV-I proviral load
      were very low in them. The heightened transmigrating activity of CD4+ cells from
      HAM patients through reconstituted basement membrane is based on the increased
      activity of aminopeptidase-N. Collectively, these findings suggest that HTLV-I
      infected CD4+ T cells play an important role in the early stage of the
      pathogenesis of HAM.

PMID- 9154640
TI  - Deficient expression of antibodies specific for bacterial DNA by patients with
      systemic lupus erythematosus.
AB  - Antibodies to DNA occur commonly in the sera of normal human subjects and bind to
      nonconserved sites exclusive to DNA from certain bacterial species. These
      antibodies are primarily IgG2 and differ from anti-DNA antibodies in systemic
      lupus erythematosus (SLE) sera, which are primarily IgG1 and bind conserved sites
      on all DNA. To investigate the immune response to bacterial DNA in SLE,
      antibodies to single-stranded DNA from Micrococcus lysodeikticus (MC) were
      measured in normal human subjects and in SLE sera by enzyme-linked immunosorbent
      assay either directly or following absorption by cellulose bearing calf thymus
      (CT) DNA; isotype-specific reagents were used to assess the IgG2 response. In
      these assays, SLE sera had a marked deficiency in antibodies specific for MC
      single-stranded DNA as demonstrated by the reduction of antibody levels by CT DNA
      cellulose absorption. Furthermore, IgG2 anti-DNA in SLE sera were cross-reactive
      with MC and CT single-stranded DNA, whereas IgG2 anti-DNA in normal human
      subjects' sera were specific for the bacterial DNA antigen. Together, these
      findings indicate that SLE patients have a marked deficiency in the production of
      antibodies specific for bacterial DNA antigen. This deficiency could predispose
      to anti-DNA autoantibody production and result from tolerance defects that
      distort the array of specificities in the B-cell repertoire.

PMID- 9154641
TI  - Delivery of primary autologous skeletal myoblasts into rabbit heart by coronary
      infusion: a potential approach to myocardial repair.
AB  - Myocardial repair after injury is limited because the adult heart cannot
      regenerate. We propose using autologous skeletal muscle cells (myoblasts) as a
      source of reserve cells for repair of regions of damaged myocardium. This report
      examines two potential methods for the transfer of cells to the myocardium:
      selective coronary catheterization, and myoblast infusion or myoblast injection
      directly into the left ventricular wall. Autologous, primary rabbit skeletal
      myoblasts were harvested, were transduced ex vivo with adenoviruses expressing
      the Escherichia coli beta-galactosidase (beta-gal) gene, and were infused
      selectively into the coronary circulation or injected directly into the
      myocardial wall. After either delivery method, beta-gal expression was detectable
      at the earliest times examined (3 days) and persisted for several weeks. The
      method of delivery influenced the spatial pattern of beta-gal expression. After
      direct injection, a localized concentration of myoblasts that decreased with
      distance from the injection site was visible primarily in the myocardial layer of
      the ventricle, although occasional staining could be detected in other layers.
      After coronary infusion, discrete punctate or linear foci of beta-gal expression
      were found throughout the distribution of the left coronary circulation in all
      cardiac layers. After infusion or injection, beta-gal-positive cells were seen in
      direct physical apposition to cardiocytes; interestingly, beta-gal could be
      detected also in some branched cells with clear cross-striations. Autologous
      myoblasts survived with no obvious dysrhythmic effects despite their presence in
      extensive or discrete loci in the myocardium. These observations provide the
      first evidence that myoblast transfer is possible by catheter-based methods, and
      they create the basis for studies to investigate the functional consequences of
      myoblast infusion in damaged heart.

PMID- 9154642
TI  - Prevention of bleomycin-induced lung injury in rats by keratinocyte growth
      factor.
AB  - Intratracheal instillation of bleomycin produces pulmonary fibrosis in rats.
      Alveolar type II cell proliferation is thought to minimize the fibrotic response
      after lung injury. Because keratinocyte growth factor (KGF) stimulates type II
      cell proliferation in the rat, we designed experiments to evaluate whether
      intratracheal KGF before or after intratracheal bleomycin would prevent pulmonary
      fibrosis. Intratracheal bleomycin without KGF resulted in moderate to severe lung
      injury and subsequent fibrosis. Conversely, intratracheal KGF pretreatment at 48
      or 72 hr before bleomycin resulted in minimal to no visible lung injury. Rats
      pretreated with phosphate buffered saline before bleomycin had significantly more
      neutrophils and protein in bronchoalveolar lavage fluid at 4 and 6 days and
      higher hydroxyproline levels after bleomycin as compared to KGF-pretreated rats.
      Pretreatment with KGF at 48 hr protected against bleomycin-induced alterations in
      pulmonary physiology and increased surfactant protein C-positive (SP-C)-positive
      cells and SP-A, SP-B, SP-C, and SP-D mRNA levels after bleomycin instillation
      when compared to saline pretreated rats on day 1 or day 7. KGF posttreatment
      protocols did not prevent bleomycin lung injury and fibrosis. We conclude that
      KGF pretreatment attenuates bleomycin lung injury and increases type II cell
      proliferation and surfactant protein gene expression after bleomycin instillation
      in the rat.

PMID- 9154643
TI  - A bradykinin antagonist inhibits both bradykinin- and the allergen-induced airway
      response in primates.
AB  - Bradykinin is a mediator of bronchoconstriction and may play a role in the
      development of the asthmatic response after antigen challenge. Our objective was
      to study the effectiveness of NPC 17731 as a specific bradykinin beta 2-receptor
      antagonist and as an antagonist of the allergen-induced early phase of asthma. A
      primate model was used for all studies. Intracutaneous end-point titrations were
      performed with bradykinin. A shift of the bradykinin end-point titer was seen
      when NPC 17731 was injected by the intradermal route prior to performing the end
      point titration. Using an aerosolized bradykinin or Ascaris suum antigen airway
      threshold challenge system, inhibition of the bradykinin or Ascaris airway
      response was evaluated after pretreatment with aerosolized NPC 17731. NPC 17731
      proved to be a safe, effective specific bradykinin receptor antagonist in both
      cutaneous and airway challenges. NPC 17731 was able to inhibit the antigen
      induced airway response in the primate. Bradykinin may play a larger role in
      mediating the early phase of the antigen-induced asthmatic response than
      previously was appreciated.

PMID- 9154644
TI  - The predominance of beta (CC) chemokine transcripts in idiopathic inflammatory
      muscle diseases.
AB  - Cytokines and chemokines that upregulate major histocompatibility complex class I
      antigens, recruit lymphocytes, and enhance T-cell-mediated myotoxicity may be
      important in the pathogenesis of dermatomyositis and polymyositis. We searched
      for cytokine and chemokine transcripts in inflammatory muscle specimens from 14
      newly diagnosed or treated patients. Control specimens from six patients without
      inflammatory muscle disease were analyzed for transcripts of interleukins-1 beta,
      -2, -4, -6, -10, and -15, and interferon-gamma, tumor necrosis factor-alpha,
      transforming growth factor-beta 1, macrophage inflammatory proteins-1 alpha and 
      1 beta (MIP-1 alpha, MIP-1 beta), and the chemokine "regulated on activation,
      normally T expressed and secreted" (RANTES). Surprisingly, the proinflammatory
      and lymphocyte cytokines were detected only sporadically in myositis muscle
      specimens, and their presence did not correlate with disease activity or
      treatment status of the patient. In contrast, MIP-1 alpha and MIP-1 beta were
      detected in 13 and 6 myositis biopsies, respectively, and RANTES, another beta
      (CC) chemokine, was detected in eight myositis biopsies. This study and other
      reports of low levels of acute-phase cytokines in myositis patients suggest that
      the proinflammatory cytokines do not play a major role in ongoing muscle damage.
      The CC chemokines studied here, in particular MIP-1 alpha, might contribute to
      ongoing muscle inflammation, and the pathogenesis of inflammation in myositis may
      follow a previously unrecognized pathway.

PMID- 9154645
TI  - In vivo gene expression of type 1 and type 2 cytokines in synovial tissues from
      patients in early stages of rheumatoid, reactive, and undifferentiated arthritis.
AB  - It has been reported that the mRNA of the type 1 cytokine, interferon-gamma (IFN
      gamma)--but not the type 2 cytokine interleukin-4 (IL-4)--is detected in synovial
      tissues of rheumatoid arthritis (RA) patients, whereas both IFN-gamma and IL-4
      mRNA are detected in reactive arthritis (ReA). To evaluate such data more
      extensively, we obtained 208 synovial specimens in a prospective study of 52
      early synovitis patients (13 RA, 11 ReA, 28 undifferentiated oligoarthropathy)
      and analyzed type 1 and type 2 cytokine mRNA expression in specimens containing
      sufficient mRNA. Using a nested reverse transcriptase polymerase chain reaction
      technique, we measured the relative mRNA levels of 10 cytokines and CD3 delta
      chain. We detected IL-10, IL-15, and CD3 delta chain mRNA in all RA and ReA
      patients and frequently detected tumor necrosis factor-alpha, IL-1 beta, and IFN
      gamma mRNA. IL-6 and IL-12 p40 mRNA were detected in approximately one-half of
      the patients. We also detected greater amounts of IL-2 and IFN-gamma mRNA in ReA
      than were detected in RA. However, we rarely detected IL-4 or IL-13 mRNA. Similar
      cytokine profiles were observed in undifferentiated oligoarthropathy. The amounts
      of cytokine mRNAs, except for IL-10, in specimens from the patients taking
      prednisone or second-line antirheumatic drugs tended to be less than in specimens
      from the patients taking neither prednisone nor second-line antirheumatic drugs.
      These results suggest that cytokine mRNA profiles in patients with RA, ReA, and
      undifferentiated arthritis in their early stages are skewed toward
      proinflammatory macrophage-derived and type 1 cytokines. IL-10--not IL-4 or IL-13
      -mRNA appears to be the major antiinflammatory cytokine mRNA. Drug therapy is
      associated with depressed proinflammatory and type 1 cytokine mRNA production.
      The differences in the expression of IL-2 and IFN-gamma mRNA between RA and ReA
      may reflect unique etiological or host factors associated with the early stages
      of these diseases.

PMID- 9154646
TI  - Membership of the Association of American Physicians.

PMID- 9154647
TI  - Race, self-disclosure, and "forbidden talk": race and ethnicity in contemporary
      clinical practice.
AB  - In this paper I attempt to extend the psychoanalytic conversation about race and
      ethnicity by discussing the intersubjectivity of race and racial difference. I
      present clinical material from an interracial treatment in which disclosures
      about race played an important role in deepening the clinical process. The
      resulting interactions permitted the patient to admit more of herself into the
      treatment space. I suggest that contemporary psychoanalytic formulations and
      multicultural perspectives from outside of psychoanalysis can together create
      more meaningful conceptualizations which take into account the lived realities of
      race and the ways in which these may be shaped by individual psychology.

PMID- 9154648
TI  - Play in the treatment of adolescents.
AB  - I propose a view of the treatment process with adolescents which places
      interactive play at the center. The adolescent plays by creating a highly charged
      interpersonal drama with the analyst to work out specific developmental
      conflicts. These conflicts involve struggles for greater autonomy and the
      formation of a solid sense of identity in the face of regressive pulls. The
      analyst unwittingly is taken up in the play and uses his or her sense of
      involvement as material for interpretation to further the play or resolve periods
      of strain when play falters.

PMID- 9154649
TI  - On knowing what one knows.
AB  - The author presents vignettes of a type of experience that is familiar to many
      analysts. He suggests that analysts and analysands know much more about each
      other than is generally recognized and that much of the important communication
      is subliminal, out of conscious awareness. Evidence of our unconscious knowledge
      surfaces in the form of emotion, fantasy, images, intrusive thoughts, and
      physical feelings. Often it seems uncanny. Recent experimental evidence and
      neurobiological research seem to explain and validate these analytic experiences.

PMID- 9154650
TI  - Interpretation as comparison.
AB  - Analytic subjectivity may not be the problem it seems. What is crucial for
      patients is not that analysts possess the objective truth, but that patients see
      a truth for themselves. How they accomplish this may depend on the analyst's
      showing them a view of themselves that differs from their own and can be compared
      to it. Each aspect of experience is defined by its relation to another reference
      point. I propose that the interpretive process is a medium for knowing one's mind
      in relation to that of another. This has implications for issues of analytic
      authority and autonomy.

PMID- 9154651
TI  - Beyond empathy: confronting certain complexities in self psychology theory.
AB  - Empathy is often a poorly understood concept. While some feel its value to
      psychoanalysis cannot be overstated, others feel it has been overemphasized as
      has the value of properly managing empathic failures that arise during an
      analysis. This paper will attempt to (1) demonstrate how patients sometimes
      resist empathy and erect barriers to being understood; (2) illustrate how empathy
      may sometimes be unachievable due to the difficulties encountered when one tries
      to empathize with the various aspects of another's experience that are in
      conflict with one another; and (3) propose that analysts may need to go beyond
      the common definition of empathy in order to help patients question and discard
      certain cherished beliefs they hold about themselves.

PMID- 9154652
TI  - How can we study the efficacy of psychoanalysis?
AB  - Psychoanalytic efficacy has been demonstrated in general, but not in comparison
      with other therapies, nor with detailed study of the relationship between process
      and outcome. The steps necessary to accomplish such studies are outlined, along
      with a review of our present readiness. Crucial dimensions of such work are
      explored, including the use of single case studies, and ways of looking at
      sequences of interaction between analyst and patient as they change during
      various phases of treatment. Methods of using control and comparison groups and
      follow-up studies are described, and various promising specific strategies are
      proposed.

PMID- 9154653
TI  - IgA nephropathy--human disease and animal model.
AB  - IgA nephropathy is one of the most common chronic glomerulonephritides worldwide.
      Since the first publication on IgA nephropathy, a number of clinical and
      pathological investigations have revealed that the clinical course of patients
      with IgA nephropathy is extremely diverse, with approximately 10-20% of the
      patients developing end-stage chronic renal failure. Glomerular changes similar
      to IgA nephropathy have also been observed in patients with Schoenlein-Henoch
      purpura, and with other diseases such as liver cirrhosis and chronic inflammatory
      diseases of the lung. The broad spectrum of clinical and pathological features of
      IgA nephropathy encompasses a syndrome which includes both primary and secondary
      IgA nephropathy. The common etiology and pathogenesis of primary and secondary
      IgA nephropathy appear to be closely related to immunological abnormalities in
      the production of IgA induced by antigenic stimulation of the common mucosal
      immune system. IgA is one of the most important humoral factors of the mucosal
      immune defense system and functions as an antibody against various extrinsic and
      intrinsic substances. This review describes the Arthus type of IgA immune complex
      deposition in the glomeruli which can result from persistent or repeated
      increases in circulating IgA immune complexes. The latter occurs as a consequence
      of overproduction of IgA antibodies and/or impairment in clearance of IgA immune
      complexes by the mononuclear phagocytic system. The present review also focuses
      on the biology of the IgA-mediated immune system and on the etiology,
      pathogenesis, and animal models of IgA nephropathy.

PMID- 9154654
TI  - Time course of renal glutathione levels in experimental Fanconi syndrome: an
      enzyme-based approach.
AB  - Time-dependent alterations in glutathione (GSH) concentration and the activities
      of several key enzymes of GSH metabolism were studied in a rat model of
      experimental Fanconi syndrome induced by i.p. injection of sodium maleate (400
      mg/kg BW). The changes in the parameters tested were monitored 0, 2, 4, and 12 h
      after sodium maleate administration. A significant decrease in renal GSH level
      was observed 2 and 4 h after sodium maleate treatment (27% and 38% of control
      values, respectively). The renal GSH depletion did not appear to be due to the
      decreased production rate or to an increased degradation of the tripeptide. This
      suggestion is based on the findings that the activities of the GSH synthesis
      (gamma-glutamyl cysteine synthetase and glutathione reductase) and those of the
      catabolic pathways (gamma-glutamyl transpeptidase) were unaltered at the same
      time points. The unchanged activity of gamma-glutamyl transpeptidase also
      suggests preserved luminal membrane integrity in experimental Fanconi syndrome.
      The decreased activity of glutathione peroxidase, which utilizes GSH as a
      cosubstrate in the course of inactivation of free radicals, in the first hours
      after treatment could facilitate lipid peroxidation reactions in this model of
      acute renal failure. The observed changes in all parameters tested were
      transient, with recovery to baseline levels in a period of 12 h after sodium
      maleate administration. At the same time a pronounced functional impairment still
      existed. The beneficial effect of fast recovery of renal GSH level on the
      functional and morphological restitution in experimental Fanconi syndrome is
      suggested.

PMID- 9154655
TI  - Heparin decreases blood pressure and response to exogenous endothelin but does
      not protect against chronic experimental cyclosporine nephropathy.
AB  - Cyclosporine nephrotoxicity is caused by renal arteriolar vasoconstriction and
      tubulointerstitial fibrosis. Endothelin has been proposed as a major mediator of
      these phenomena. Heparin inhibits vascular smooth muscle cell proliferation and
      lowers blood pressure by regulating endogenous endothelin 1 production. In a
      model of chronic cyclosporine nephrotoxicity in the rat, animals were treated
      with cyclosporine alone, cyclosporine plus heparin, and heparin alone for 28
      days. Independent experiments determined that these doses of heparin resulted in
      a marked decrease in responsivity to exogenous endothelin. Despite this, there
      were no beneficial effects on renal structure or function in this animal model of
      chronic cyclosporine nephrotoxicity. Thus, the role of endothelin in the
      pathogenesis of the chronic tubulointerstitial changes and arteriolopathy in this
      model is probably minor.

PMID- 9154656
TI  - Hepatic and extrahepatic angiotensinogen gene expression in rats with acute
      nephrotic syndrome.
AB  - Plasma concentration and urine excretion of the renin-angiotensin system proteins
      are altered in rats with nephrotic syndrome (NS). In this work the messenger
      ribonucleic acid (mRNA) levels of angiotensinogen (Ao) were analyzed with the
      slot-blot hybridization technique in liver and other extrahepatic tissues:
      kidney, heart, brain, and adrenal gland from control, nephrotic, and pair-fed
      (PF) rats. NS was induced by a single injection of puromycin amino-nucleoside
      (PAN). Although a great urinary excretion and half-normal plasma levels of Ao
      were observed on day 6 after PAN injection, when NS was clearly established,
      hepatic Ao mRNA levels did not change. Furthermore, the Ao mRNA levels did not
      change in any of the extrahepatic tissues studied on day 6, nor did its hepatic
      levels at days 1, 3, 5, or 7 after PAN injection. These data suggest that the
      hepatic and extrahepatic Ao mRNA levels are unaltered during the development of
      the acute NS induced by PAN.

PMID- 9154657
TI  - Renal injury mediated calcium oxalate nephrolithiasis: role of lipid
      peroxidation.
AB  - The role of lipid peroxidation (LPO) in renal tubular damage mediated calcium
      oxalate retention was investigated in a rat model. Hyperoxaluria, without
      deposition of oxalate in kidney, was induced by administration of ethylene glycol
      (EG), a precursor of oxalate. Oxidative stress condition was produced by
      administration of buthionine sulfoximine (BSO), an inhibitor of glutathione
      biosynthesis. BSO-treated rats showed a significant (p < 0.001) increase in LPO
      over EG-treated rats and it was almost doubled in BSO + EG treated rats. LPO was
      accompanied by significant urinary excretion of renal damage marker enzymes such
      as gamma-glutamyl transpeptidase (gamma-GT), alkaline phosphatase (ALP) and
      cathepsin D, mucoproteins, and glycosaminoglycans (GAGs) in the BSO and BSO + EG
      groups but not in the EG group. Urinary excretion of gamma-GT (r = +0.90) (p <
      0.001) and deposition of oxalate (r = +0.78) (p < 0.001) in kidney positively
      correlated with LPO. These results suggest that LPO initiates renal damage,
      thereby leading to calcium oxalate retention and stone formation.

PMID- 9154658
TI  - Biochemical bone markers, bone mineral content, and bone mineral density in rats
      with experimental nephrotic syndrome.
AB  - The human nephrotic syndrome (NS) is accompanied by important alterations of
      mineral and bone metabolism. The purpose of the present study was to examine bone
      metabolism in rats with experimental NS and normal creatinine clearance, and to
      evaluate the reversibility of this alteration. NS was induced by three injections
      of puromycin aminonucleoside (PAN) on days 0, 21, and 35 (10, 5, and 5 mg/100 g
      body weight, respectively). The biochemical markers of bone formation
      (osteocalcin and alkaline phosphatase) and bone resorption (hydroxyproline and
      pyridinoline), bone mineral content (BMC), and bone mineral density (BMD),
      determined by dual-energy x-ray absorptiometry (DEXA), were studied on days 0, 7,
      14, 28, 42, 56, 84, and 112. Proteinuria was present throughout the study.
      Hypoproteinemia was seen on days 7, 28, 42, and 56, returning to control values
      on days 84 and 112. In serum, osteocalcin (OC) concentration increased (p <
      0.001), and alkaline phosphatase (ALP) decreased (p = 0.002). In urine,
      hydroxyproline increased (p < 0.001), but urinary pyridinoline was not different
      from the control group throughout the study. Increased serum parathyroid hormone
      concentration and decreased levels of 25-hydroxy and 1,25-dihydroxyvitamin D were
      found from day 7. During the intense proteinuria, bone resorption predominates
      and decreased BMC and BMD ensues in PAN-nephrotic rats. PAN-nephrotic rats showed
      low BMC and BMD compared to control group (p < 0.001). At the end of the study,
      when proteinuria persisted but total serum protein returned to control values,
      the biochemical bone markers, BMC, and BMD returned to normal. In conclusion, PAN
      nephrotic rats had reversible bone alterations that were related to the magnitude
      of proteinuria and the concentration of total serum protein.

PMID- 9154659
TI  - Betamipron reduces cisplatin nephrotoxicity in rodents without modifying its
      antileukemic activity in mice.
AB  - Protective effects of betamipron (BP, N-benzoyl-beta-alanine), one of a series of
      N-acyl amino acids, on cisplatin-induced nephrotoxicity were examined. Since the
      damage observed in the kidney is localized to the proximal tubule cells, we
      investigated the influence of BP on urinary enzymes and excreta. Male Wistar rats
      and ddY mice were injected i.p. with 6 mg/kg and 16 mg/kg, respectively, of
      cisplatin combined with an i.p. 250 mg/kg BP dose. The toxicity of cisplatin as
      indicated by body weight gain, blood urea nitrogen, and serum creatinine levels
      was significantly (p < 0.05) suppressed by administration of BP after cisplatin
      treatment. The increase in urinary N-acetyl-beta-D-glucosaminidase activity,
      increase and subsequent decrease in gamma-glutamyl transferase activities, and
      increase in beta 2-microglobulin level observed after treatment with cisplatin
      were suppressed by administration of BP after cisplatin treatment. The
      combination of cisplatin and BP had no apparent effect on the efficacy of
      cisplatin against P388 leukemic cells in mice.

PMID- 9154660
TI  - Acute renal failure caused by nontraumatic rhabdomyolysis.
AB  - Nontraumatic rhabdomyolysis may be associated with severe metabolic disturbances.
      In particular, previous literature has described a 8-20% incidence of acute renal
      failure in rhabdomyolysis. The aim of this study was to evaluate our experience
      on 11 patients with acute renal failure treated by high-efficiency daily
      hemodialysis.

PMID- 9154662
TI  - Complete success of intradermal vaccination against hepatitis B in advanced
      chronic renal failure and hemodialysis patients.
AB  - Incomplete protection and response variability have been reported in chronic
      renal failure (CRF) and hemodialysis (HD) patients vaccinated against hepatitis B
      with the recombinant vaccine (rHBV). We vaccinated 12 consecutive patients (7 CRF
      and 5 HD), 7 males and 5 females, 61 years old (range 22-82); HD patients were on
      treatment from 1 to 12 months. CRF patients had a residual renal function
      (creatinine clearance) of 11 +/- 3 mL/min. Six patients had been already
      vaccinated unsuccessfully, as defined by the absence of detectable specific
      antibody S (Abs) 1 month after the completion of vaccination by the classical
      intramuscular method, with a median of 7 (range 3-18) doses of 20 micrograms.
      rHBV was given intradermally (i.d.) at the dose of 5 micrograms every fortnight
      up to 8 doses or until titers of Abs rose above 1000 mIU/mL. Levels above 10
      mIU/mL were considered as protective. Abs titers were monitored during the whole
      vaccination period every 15 days and at the 1st, 3rd, and 6th month after its
      completion. Median number of i.d. doses given was 7 (range 4-8). Antibody titers
      rose gradually; surface antibodies (AbS) were detected as early as the end of the
      first month (2nd dose). Age and sex had no influence on the immune response, its
      duration, or antibody titers. i.d. administration of rHBV in repeated small
      injections was found to be absolutely effective, in both CRF and HD patients. AbS
      titers after multiple i.d. vaccination rose gradually in CRF and HD patients, and
      were protective for at least 6 months after the last injected dose. Protective
      levels were achieved even in patients not responding to multiple-double quantity
      intramuscular (i.m.) doses. Patients with stronger initial response to the
      vaccine (after the 4th dose) gave significantly higher AbS titers (at least in
      50% of the follow-up measurements), although they received fewer injections and
      smaller total dose of vaccine.

PMID- 9154661
TI  - Impact of continuous hemofiltration on cytokines and cytokine inhibitors in
      oliguric patients suffering from systemic inflammatory response syndrome.
AB  - The impact of continuous hemofiltration (CHF) using a polyacrylonitrile membrane
      on the kinetics of tumor necrosis factor alpha (TNF alpha), interleukin-1 beta
      (IL-1 beta), and their inhibitors (soluble TNF receptors [sTNFrI, sTNFrII],
      interleukin-1 receptor antagonist [IL-1Ra]) was assessed in nine oliguric
      patients suffering from systemic inflammatory response syndrome. Blood and plasma
      flow (Qb, Qp), sieving coefficient (SC), plasma and ultrafiltrate clearances (Kp,
      Kuf), and plasma extraction rates (ERp) were calculated at different time points
      using standard formulas. No significant improvement of hemodynamics or gas
      exchange was noted following HF but a significant increase in serum bicarbonate
      occurred after 24 h (P < 0.05). TNF alpha was detected in plasma from all
      patients (153 +/- 2.3 pg/mL [mean +/- SEM]). None of the patients had detectable
      IL-1 beta levels. High levels of the TNF receptors (sTNFrI 20.338 +/- 2.431
      pg/mL; sTNFrII 17.839 +/- 2.630 pg/mL) and IL-1Ra (19.775 +/- 3.943 pg/mL) were
      found in all patients. Upon initiation of hemofiltration (HF), the mean
      individual sTNFrI/TNF alpha ratio amounted to 269 +/- 84.6 and the sTNFrII/TNF
      alpha ratio to 249 +/- 91.8. Mean ultrafiltrate volume (Vuf) was 11.8 +/- 0.4
      L/day. Appreciable sieving of IL-1Ra (SC 0.45 +/- 0.10), but not of the other
      cytokines, was noted (SC TNF alpha, sTNFrI, sTNFrII < 0.09). Despite minimal Kuf
      of TNF alpha, sTNFrI, and STNFrII (Kuf < 0.8 mL/min), appreciable Kp was noted,
      suggesting that membrane adsorption occurs (Kp approximately 8 mL/min). There was
      a nonsignificant increase of the ratios between both TNF receptors and TNF alpha
      across the filter (sTNFrI/TNF alpha ratio [pre] 231 +/- 37.9 versus [post] 312 +/
      75.3); sTNFrII/TNF alpha ratio [pre] 211 +/- 42.1 versus [post] 291 +/- 79.3).
      Appreciable Kp of IL-1Ra was noted (Kp 17.3 +/- 1.61 mL/min), which was only in
      part due to Kuf (4.0 +/- 0.86 mL/min). There was a significant decrease of IL-1Ra
      levels across the membrane, both overall ([pre] 20.223 +/- 2.282 versus [post]
      16.637 +/- 2.039 pg/mL; P < 0.01) and at different time points (P < 0.01). Only
      for IL-1Ra was significant extraction from plasma noted (ERp 26 +/- 6.0%). Plasma
      levels of TNF alpha, sTNFrI, sTNFrII, and IL-1Ra were not altered by 24 h of CHF.
      In conclusion, both cytokines and cytokine inhibitors can be removed from the
      circulation, either by convective transport or by membrane adsorption. Using low
      volume HF (Vuf approximately 12 L/day), no impact on cytokine plasma levels nor
      the patients hemodynamics or gas exchange was noted. The appreciable SC of IL-1Ra
      (0.45), however, suggests that HF with high(er) UF volumes (> 50 L/day) may be
      able to achieve reductions in plasma levels of some peptide (anti)mediators.
      However, whether this aspecific elimination of both mediators and antimediators
      may alter the clinical course in critically ill patients remains to be
      investigated.

PMID- 9154663
TI  - Acute renal failure in recipients of organ transplantation and nontransplantation
      patients: comparison of characteristics and mortality.
AB  - Mortality from acute renal failure in critically ill patients remains in excess
      of 50% despite decades of improvement in supportive care. It is not known whether
      replacement of other failing organs by non-renal organ transplantation affects
      mortality in acute renal failure. We retrospectively reviewed the course of 169
      patients with acute renal failure managed at a single university medical center
      over a 1-year period. Measures of disease severity (need for renal replacement
      therapy, mechanical ventilation or parenteral nutrition, presence of oliguria and
      APACHE II scores) and final outcome were compared in 97 patients with acute renal
      failure who did not receive transplants and 72 patients with acute renal failure
      who underwent non-renal solid organ transplants. Overall mortality was 50.3% and
      directly correlated with APACHE II score. Compared to nontransplant patients,
      transplant recipients were younger. more frequently male, and less often
      oliguric; but the groups were similar in mean APACHE II scores and need for renal
      replacement therapy, prolonged mechanical ventilation, and parenteral nutrition.
      Overall, mortality was significantly lower for transplant patients compared to
      nontransplant patients (34.7% vs. 61.9%, p < 0.05). In nonoliguric acute renal
      failure and renal failure not requiring renal replacement therapy, mortality was
      low and similar in both transplant and nontransplant patients. Compared to
      nontrasplant patients with similar risk factors and similar APACHE II scores,
      mortality was significantly lower for transplant patients who were oliguric, or
      who required renal replacement therapy, mechanical ventilation, or parenteral
      nutrition. Organ transplantation is associated with a survival advantage in acute
      renal failure when compared to the outcome of critically ill nontransplant
      patients. The relation between APACHE II scores and survival is altered by
      transplantation.

PMID- 9154664
TI  - Early gestational hemolytic uremic syndrome: case report and review of
      literature.
AB  - Hemolytic uremic syndrome (HUS) is a rare condition which most frequently follows
      gastrointestinal or respiratory infection episodes in young children, but it can
      also occur in other settings such as the postpartum period and during use of
      drugs such as oral contraconceptives, immunosuppressors, and antineoplastics. In
      early pregnancy, however, its frequency is thought to be very low. The authors
      report a case of a 30-year-old woman who developed HUS early in her first
      pregnancy. She had persistent aqueous diarrhea from the beginning of the
      pregnancy. At the 21st week she developed hypertension which in 2 weeks was
      followed by seizures, oliguria, and acute pulmonary edema despite intensive
      medical efforts to control her blood pressure. Surgical intervention for fetal
      delivery was performed. The patient was initially kept on continuous hemodialysis
      (CVVHD) followed by an alternate-day conventional hemodialysis schedule. A
      peripheral blood analysis showed a microangiopathic hemolytic anemia with
      thrombocytopenia; blood coagulation tests were completely normal. A brain CT scan
      and an abdominal MRI showed no major abnormalities. HUS was confirmed by a
      percutaneal kidney biopsy, performed at the 21st day of anuria. Techniques for
      identification of verotoxin-producing E. coli were not available. Renal function
      did not recover and the patient has been undergoing regular maintenance
      hemodialysis for a year.

PMID- 9154665
TI  - IgA myeloma associated with decreased anion gap and renal failure.
AB  - The anion gap in myeloma patients had been well studied. IgG myeloma usually has
      decreased anion gap, whereas IgA myeloma always presents with normal anion gap.
      We report an unusual presentation of IgA myeloma with decreased anion gap and
      renal failure due to superimposing of acetazolamide-related bicarbonate loss.

PMID- 9154666
TI  - Unusual presentations of extrapulmonary tuberculosis in three hemodialysis
      patients.
AB  - We report three patients who received maintenance hemodialysis and suffered from
      extrapulmonary tuberculosis with unusual presentations. The first patient
      presented with fever of unknown origin. All studies showed negative findings
      except high erythrocyte sedimentation rate and high value of C-reactive protein.
      He failed to response to broad-spectrum antibiotics but showed a complete
      response to antituberculosis therapy. The second patient presented with right
      supraclavicular lymphadenopathy and weakness. Lymph node biopsy revealed
      caseating granuloma with positive acid-fast bacilli. The third patient presented
      with tumor mass of left sternoclavicular joint for which malignancy was suspected
      initially. Ultimately, tuberculosis was documented by histopathologic studies
      showing caseating granuloma. All three patients had normal findings of chest x
      ray and did not have previous history of tuberculosis and diabetes mellitus.

PMID- 9154667
TI  - Acute cortical necrosis in falciparum malaria: an unusual cause of end-stage
      renal disease.

PMID- 9154668
TI  - Renal failure, paraproteinemia, and lung squamous cell carcinoma.
AB  - A 66-year-old man presented with gastrointestinal symptoms and acute renal
      failure. He had paraproteinemia and tested positive for antinuclear antibodies.
      There was no evidence for autoimmune disorder or amyloidosis, and bone marrow
      biopsy was not consistent with multiple myeloma. Three months later he presented
      with diffuse lymphadenopathy and right lung mass, and lymph node histology
      revealed metastatic squamous cell carcinoma. This association of paraproteinemia
      and nonlymphatic neoplasia is unusual and still very rare. A review of the
      literature is presented.

PMID- 9154669
TI  - Sleep-related hypoxaemia in chronic obstructive pulmonary disease: causes,
      consequences and treatment.
AB  - Worsening of hypoxaemia during sleep in patients with chronic obstructive
      pulmonary disease has been extensively investigated in the past 20 years owing to
      the development of polysomnography and to the advent of reliable transcutaneous
      oximeters. Sleep-related hypoxaemia is characteristic of rapid-eye-movement (REM)
      sleep but may be present during other sleep stages. There is a strong
      relationship between nocturnal O2 saturation and the level of daytime PaO2: the
      more pronounced daytime hypoxaemia, the more severe nocturnal hypoxaemia. Sleep
      related hypoxaemia is due to a variable combination of alveolar hypoventilation
      and ventilation-perfusion mismatching, alveolar hypoventilation being the
      preponderant mechanism during REM sleep. The deleterious effects of sleep-related
      hypoxaemia include cardiac arrhythmias, 'hypoxaemic stress' on the coronary
      circulation and especially, peaks of pulmonary hypertension. The treatment of
      nocturnal hypoxaemia is conventional O2 therapy (both nighttime and daytime) in
      patients who exhibit marked daytime hypoxaemia (PaO2 < 55-60 mm Hg). At present
      data are not sufficient for justifying the use of isolated nocturnal O2 therapy
      in patients with nocturnal desaturation who do not qualify for conventional O2
      therapy.

PMID- 9154670
TI  - Predictive diagnostic value of clinical assessment and nonlaboratory monitoring
      system recordings in patients with symptoms suggestive of obstructive sleep apnea
      syndrome.
AB  - Obstructive sleep apnea syndrome (OSA) is of increasing importance because of its
      high prevalence and danger of morbidity to untreated patients. Diagnostic
      procedures need simplification. We evaluated the qualitative value of a stepwise
      diagnostic approach using clinical assessment and a home-based screening device
      according to current recommendations. METHODS: We investigated 114 patients with
      symptoms suggestive of obstructive sleep apnea syndrome by means of their
      clinical features, questionnaire responses, four-channel nonlaboratory monitoring
      (NLM) and full polysomnography. Operative indices in the diagnosis of OSA were
      calculated. RESULTS: A significant correlation (r = 0.7: p < 0.0001) was found
      between the oxygen desaturation index (ODI) and the respiratory disturbance index
      (RDI). The calculation of the difference between ODI by NLM and RDI by
      polysomnography showed a lack of agreement. Home-based monitoring revealed a high
      sensitivity (94%) but a low specificity (41%) in diagnosing OSA. However, a
      combination of clinical features, questionnaires and pulse oximetry achieved a
      specificity of 92%. CONCLUSION: Home-based monitoring provides reasonable
      negative predictive values in the diagnosis of OSA syndrome in symptomatic
      patients. It therefore qualifies as a screening method. Combined with clinical
      features and questionnaires it provides high positive predictive values and may
      therefore prove useful in simplifying diagnostic procedures.

PMID- 9154671
TI  - Changes in arterial and transcutaneous oxygen and carbon dioxide tensions during
      and after voluntary hyperventilation.
AB  - The purposes of our study were (1) to investigate whether a 3-min short-term
      hyperventilation leads to posthyperventilatory hypoxemia and (2) to assess the
      role of transcutaneous blood gas measurements for monitoring oxygen and carbon
      dioxide changes during the after the test. In 10 male volunteers arterial and
      transcutaneous blood gases were measured simultaneously before, during and after
      a 3-min voluntary hyperventilation maneuver. Baseline arterial PO2 increased from
      13.7 +/- 0.4 kPa (103 +/- 3 mm Hg) to 18.6 +/- 0.3 kPa (139 +/- 2.3 mm Hg; p <
      0.005 compared to baseline) during hyperventilation. After the provocation test
      posthyperventilatory hypoxemia occurred with a minimal mean value of 7.8 +/- 1.3
      kPa (58.5 +/- 9.8 mm Hg; p < 0.05 compared to baseline). Whereas close agreement
      between arterial and transcutaneous measurements was obtained for carbon dioxide
      values before hyperventilation, transcutaneous O2 consistently underestimated
      arterial O2. A short-term over-breathing of 3 min causes a significant
      posthyperventilatory hypoxemia. We hypothesize that posthyperventilatory
      hypoxemia is caused by hypopnea as a result of depleted CO2 body stores.
      Noninvasive transcutaneous blood gas measurements are not reliable for monitoring
      blood gas changes during and after hyperventilation, most probably because of the
      slow response time of the electrodes and the reflex vasoconstriction of the skin
      vessels.

PMID- 9154672
TI  - Inhibition by erythromycin of human pulmonary artery endothelial cell injury
      induced by human neutrophils.
AB  - Neutrophils are thought to play a key role in tissue injury. We investigated the
      role of human neutrophils in the induction of injury to the human pulmonary
      artery endothelial cells and the effect of erythromycin on neutrophil-induced
      endothelial cell damage. Incubation of unstimulated neutrophils with endothelial
      cells increased the release of lactate dehydrogenase (LDH) activity and preloaded
      fura-2 from endothelial cells. When neutrophils were activated by phorbol
      myristate acetate, the release of LDH and fura-2 was enhanced further. Superoxide
      dismutase partially inhibited the release of LDH and fura-2 induced by
      neutrophils, whereas erythromycin markedly inhibited the release of endothelial
      cell LDH and fura-2 induced by neutrophils. These results suggest that
      endothelial cell injury is, at least in part, mediated by the action of
      superoxide and that erythromycin protects against neutrophil-induced endothelial
      cell injury.

PMID- 9154673
TI  - Role of sensory neuropeptides in PIV-3-infection-induced airway
      hyperresponsiveness in guinea pigs.
AB  - Viral respiratory tract infections are known to induce transient airway hyper
      responsiveness. The role of the nonadrenergic noncholinergic neuropeptide system
      on virus-induced airway hyperresponsiveness was studied in the guinea pig. Ten
      guinea pigs were inoculated with parainfluenza 3 virus (PIV-3.2 x 10(6) PFU) by
      nasal route. 16 animals served as untreated controls. Viral infection was proven
      by histological changes and by demonstration of viral antigen using
      immunohistochemical techniques. Four days after inoculation, airway
      responsiveness to inhaled acetylcholine (ACH) aerosol was measured in
      anesthetized and tracheotomized guinea pigs. The ACH concentration which produced
      an increase of 100% in pulmonary resistance (PC100 RI) and in dynamic elastance
      (PC100 Edyn) was calculated from a 5-step ACH dose-response curve (0.125, 0.25,
      0.5, 1.0 and 2.0% ACH). Two further groups of 8 PIV-3-infected guinea pigs and 8
      noninfected control animals were pretreated with capsaicin in increasing doses
      (50, 100, 125 and 150 mg/kg) on 4 consecutive days starting 6 days before virus
      inoculation. Measurements of airway responsiveness to ACH were performed 4 days
      after virus inoculation. Another 5 uninfected control animals were pretreated
      only with the solvent for capsaicin and inoculated with virus-free cell
      supermatant. PIV-3 infection increased airway responsiveness to ACH compared to
      noninfected controls [PC100 RI 0.81 vs. > 2.0% ACH (median). p < 0.002 PC100 Edyn
      0.52 vs. 1.07% ACH (median), p < 0.01]. In capsaicin-pretreated PIV-3-infected
      animals, airway hyperresponsiveness was completely prevented compared to the
      virus-infected group without capsaicin pretreatment (PC100 RI > 2.0 vs. 0.81%
      ACH, p < 0.01; PC100 Edyn 1.42 vs. 0.52% ACH p < 0.01). As neuropeptide depletion
      with capsaicin completely prevented the increase in airway constrictory response
      to ACH following virus infection, we conclude that neuropeptides are effectively
      involved in PIV-3-induced airway hyperresponsiveness in the guinea pig.

PMID- 9154674
TI  - Effectiveness of immunomodulating treatment (thymostimulin) in chronic
      obstructive pulmonary disease.
AB  - We conducted a prospective randomized study to assess the effect of thymostimulin
      in patients with long-standing chronic obstructive pulmonary disease (COPD)
      during a 1-year follow-up. A total of 38 patients in the intervention group and
      40 in the control group received standard treatment for COPD. Patients in the
      intervention group were also given thymostimulin intramuscularly (1 mg/kg day for
      the 1st week followed by once a week for 6 months). At the end of the study
      period, patients treated with thymostimulin showed a statistically significant
      lower number of exacerbations and hospital admissions as compared with controls.
      However, there were no changes in the number of patients with severe or moderate
      impairment of respiratory function throughout the study period. No significant
      differences were found by Multitest or in serum concentrations of immunoglobulins
      and T-cell subsets before and after thymostimulin treatment. We conclude that
      treatment with thymostimulin is effective in the prevention of COPD exacerbations
      acting on the cellular immune response involved in bronchopulmonary defense.

PMID- 9154676
TI  - Nocturnal arterial oxygen desaturation secondary to a sphenoidal meningioma.
AB  - We report the case of a nonobese and nonsmoking 51-year-old man with nocturnal
      arterial oxygen desaturation that returned to normal after sphenoidal meningioma
      resection. He presented an important daytime hypersomnia and episodes of
      nocturnal apnea, without snoring. His arterial blood gases, mechanical properties
      of the respiratory system pulmonary diffusing capacity and chemosensitivity were
      normal. The most frequent causes of nocturnal hypoxemia are examined.

PMID- 9154677
TI  - Simultaneous bilateral spontaneous pneumothorax in a patient with peritoneal and
      pleural papillary mesothelioma.
AB  - Simultaneous bilateral spontaneous pneumothorax (SBSP) occurred in a patient with
      papillary mesothelioma of peritoneum and pleura. The patient initially suffered
      from ascites due to peritoneal tumor studding and later presented with
      simultaneous bilateral spontaneous pneumothorax. As the disease spread from the
      abdomen to the pleural cavity, a moderate loss of histologic differentiation was
      observed.

PMID- 9154675
TI  - Hospitalized patients with community-acquired pneumonia in Hong Kong: a
      randomized study comparing imipenem/cilastatin and ceftazidime.
AB  - The aetiology and outcome of hospitalized patients with moderate to severe
      community-acquired pneumonia (CAP) were evaluated in 60 adult patients (38 male
      22 female, mean age 68.4 years). They were randomized for treatment with either
      ceftazidime or imipenem/cilastatin intravenously for 7 days. Bacteriological
      diagnoses were made in 25 cases (41.6%): Streptococcus pneumoniae (5),
      Haemophilus influenzae (5), Pseudomonas spp. in particular Pseudomonas aeruginosa
      (8), Staphylococcus aureus (4), Chlamydia spp. (2), Mycobacterium tuberculosis
      (2) and Moraxella catarrhalis (3); mixed organisms were found in 4 patients.
      Forty-two patients (70%) responded satisfactorily to the regimens with
      improvement in sputum purulence cough and dyspnoea scores; there was no
      difference in response between the two groups. Sixteen patients (26.6%) underwent
      bronchoscopy on day 4 because of inadequate response to the antibiotics regimens,
      and 9 of them (15%) required a modification of the initial treatment with
      addition of erythromycin in 5 patients vancomycin in 1 cloxacillin in 1 and
      antituberculous drugs in 2. Three out of the 60 patients (5%) died of pulmonary
      sepsis: the aetiological agents were M. tuberculosis in one, Pseudomonas
      spp./methicillin-resistant S. aureus in another, but were not identified in the
      third. We conclude that treatment with either ceftazidime or imipenem/cilastatin
      was efficacious for moderate to severe CAP in Hong Kong.

PMID- 9154678
TI  - Malignant localized fibrous tumor of the pleura occurring in a person
      environmentally exposed to tremolite asbestos.
AB  - A case is presented of a malignant localized pleural fibroma occurring in a 60
      year-old Turkish female who was environmentally exposed to tremolite. The tumor
      was excised but recurred 3 years later when it was again excised. It is possible
      that more radical surgery at initial presentation with chest wall resection would
      have been advantageous.

PMID- 9154679
TI  - Pulmonary hypoplasia presented in adulthood as a chronic respiratory failure:
      report of two cases. Embryology, clinical symptoms and diagnostic procedures.
AB  - We report 2 cases of pulmonary hypoplasia diagnosed in adulthood presenting
      clinically as chronic respiratory failure. Both patients met criteria for chronic
      bronchitis and had shown repeated respiratory infections and increasing dyspnoea.
      The spirometry showed a severe non-defined ventilatory disturbance and the
      arterial blood gases showed the presence of marked hypoxaemia. The altered chest
      X-ray, arterial blood gases and spirometry had been attributed to chronic
      bronchitis. The CT scan was instrumental in establishing the diagnosis of
      pulmonary hypoplasia.

PMID- 9154681
TI  - Pulmonary blastoma with fatal hypercalcemia.
AB  - We describe a 50-year-old, previously healthy male with metastatic pulmonary
      blastoma associated with hypercalcemic and hyperosmolar complications which
      caused his death after 5 days. The primary tumor consisted of epithelial
      [cytokeratin, beta-hCG CEA, neuron-specific enolase (NSE)-positive] and
      mesenchymal components (beta-hCG, vimentin, NSE-positive, while the metastases
      had only a mesenchymal component.

PMID- 9154680
TI  - A case of secondary pulmonary hypertension due to microscopic pulmonary tumor
      cell embolism from gallbladder carcinoma.
AB  - We describe a case of subacute cor pulmonale caused by tumor embolism from a
      gallbladder carcinoma in a 63-year-old woman. The patient was admitted to
      hospital with increasing dyspnea. Physical examination and echocardiography
      showed signs of pulmonary hypertension. She died of circulatory failure. At
      autopsy microscopic studies revealed tumor embolism in the pulmonary vessels and
      subsequent lesions causing the lethal pulmonary hypertension. This is the first
      case report of pulmonary hypertension caused by embolism from a gallbladder
      carcinoma in the literature worldwide.

PMID- 9154682
TI  - Giving all children a chance: advantages of an antiracist approach to education
      for deaf children.
AB  - This paper begins with the assumption that racism exists and influences
      educational policy and curricula in American schools, including schools for deaf
      children, and discusses bow a multicultural approach to educating deaf children
      is often limited to the description of ethnic differences. What is also needed is
      an antiracist approach to education that addresses the social and political
      ramifications of ethnic differences. It is suggested that schools for the deaf
      are in a strategic position to respond to the inadequacy of American schools to
      educate deaf children of color.

PMID- 9154683
TI  - Changing times, changing society: implications for professionals in deaf
      education.
AB  - Significant demographic shifts among school-aged deaf children in the United
      States have not mirrored similar shifts in the teaching force, which remains
      predominantly White. The importance of exposing children from ethnically diverse
      minority backgrounds to role models who have firsthand knowledge and
      understanding of issues they face is discussed and the strategies needed to
      attract minority professionals into the field of deaf education are identified.

PMID- 9154684
TI  - Asian, American, and deaf: a framework for professionals.
AB  - The authors present a multicultural framework for thinking about, assessing, and
      working with Deaf people from Asian and Asian Deaf backgrounds. Emphasis is
      placed on cultural awareness and cultural competence for professionals and on
      building bridges across cultural networks.

PMID- 9154685
TI  - Development of deaf bicultural identity.
AB  - Based on Epstein's model of self-theory, the importance of providing deaf
      children with opportunities to develop a solid deaf identity at an early age is
      discussed. Seven categories of possible identities for deaf people are outlined
      and the stages of developing a bicultural awareness presented. Case studies
      detailing these stages are discussed.

PMID- 9154686
TI  - Herstories: a preliminary look at deaf women in higher education.
AB  - This study describes the postsecondary educational experiences and perceptions of
      deaf women college students. Deaf women were interviewed using semistructured
      questions adapted from Gilligan, Lyons, and Hanmer (1990). Findings indicated
      that these deaf women perceived their college environment as generally positive,
      though they also perceived instances of unequal treatment.

PMID- 9154687
TI  - Classroom dialogues and deaf identities.
AB  - Despite increasing diversity in the classroom, many teachers of deaf and hard of
      hearing students are unprepared to teach in a way that benefits all their
      students. Our course for future teachers focuses on understanding these multiple
      identities, and on practical approaches to using diversity as an opportunity for
      class growth. Proceeding from the assumption that everyone in the classroom has
      something to teach and to learn, we describes our approach to teaching teachers
      in which we make use of the teachers' own diversity and expertise in a continuous
      dialogue across various methods. Samples of classroom dialogues are included.

PMID- 9154688
TI  - Dramatic interactions: theater work and the formation of learning communities.
AB  - This article examines the relationship of theater and dramatic study to models of
      learning communities in promoting identity, diversity, and culture. Theater is an
      example of how learning community can be achieved and levels of theater use in
      education are presented as ways in which educators can create ensemble and foster
      community. Strategies for developing learning communities using the performing
      arts are provided.

PMID- 9154689
TI  - Electronic media: broadening deaf students' access to knowledge.
AB  - Beginning with a simple explanation of the Internet the author discusses the
      advantages and disadvantages of classroom use of electronic media currently
      available. Specific strategies for applying tools, such as Listservs, are
      discussed along with teacher's responsibilities when using these media.

PMID- 9154690
TI  - The promise of the World Wide Web and other telecommunication technologies within
      deaf education.
AB  - The authors summarize a national survey that collected information on
      instructional technology resources available at schools serving deaf students in
      the United States. Results indicated that over 70% of these schools have access
      to the Internet and World Wide Web. The authors also explore innovative uses of
      the Internet and provide examples of specific applications for deaf students.

PMID- 9154691
TI  - Educational programs for deaf students.

PMID- 9154692
TI  - University and college programs for personnel in deafness.

PMID- 9154693
TI  - Programs for deaf-blind children and adults.

PMID- 9154694
TI  - Supportive and rehabilitative programs.

PMID- 9154695
TI  - [Clinical and experimental aspect of latex allergy].

PMID- 9154696
TI  - [Epidemiological research on incidence of atopic disease in infants and children
      in relation to their nutrition in infancy].
AB  - Incidence and relative risk of atopic disease (atopic dermatitis; AD, bronchial
      asthma; BA, allergic rhinitis; AR) in Japanese infants and children in relation
      to their nutrition in infancy was analyzed from the data of the epidemiological
      survey which was conducted for 10,000 mothers of infants and children in 1993. A
      total of 4,610 replies were received: 2,714 from mothers of infants (12 months
      old) and 1,896 from mothers of children (2 years old). The subjects were
      allocated to following 3 groups based on their nutrition during first 3 months
      after birth; the breast-fed group (BF), the formula-fed group (EF), the mixed-fed
      group (MF). Incidence of atopic disease in BF, FF and MF was 23.5%, 22.2% and
      21.8%, respectively and no statistical difference could be found among these 3
      groups. AD was developed 17.0%, 14.4% and 13.9%; BA was 4.4%, 8.5% and 5.2%; AR
      was 4.9%, 6.5% and 5.8% in BF, FF and MF, respectively. Incidence of AD was
      significantly different between BF and MF (p < 0.01). Incidence of BA was also
      significantly different between BF and FF (p < 0.01). Risk of onset of BA and AR
      in FF was higher (adjusted odds ratio 2.2, 95% confidence interval 1.5-3.2 and
      adjusted odds ratio 1.5, 95% confidence interval 1.0-2.2, respectively) than that
      of BF controlled by age and family history with Cochran-Mantel-Haenzel test. With
      multiple logistic regression analysis, relative risk of the onset of BA in FF at
      the age of one year was 2.1, 95% confidence interval 1.2-3.5 and at the age of
      two years old was 2.5, 95% confidence interval 1.4-4.4. These results suggest
      that the breast-fed have certain suppression effects on incidence of bronchial
      asthma in infants and children.

PMID- 9154698
TI  - [The correlation between interleukin-10 and interferon-gamma produced by
      peripheral blood mononuclear cells stimulated by house dust mite antigen in
      atopic dermatitis].
AB  - The production of interleukin (IL)-10 and interferon (IFN)-gamma by peripheral
      blood mononuclear cells (PBMC) stimulated by house dust mite (HDM)antigen and
      concanavaln A (Con A) was measured in patients with atopic dermatitis (AD). The
      HDM-stimulated PBMC from AD patients revealed to produce significantly higher
      levels of IL-10 (12 h: 918.4 +/- 206.5, 24 h: 1252.5 +/- 145.8, 72 h: 1332.7 +/-
      123.9 pg/ml) than those from normal control subjects (12 h: 231.1 +/- 139.0, 24
      h: 585.7 +/- 196.2, 72 h: 813.5 +/- 181.8 pg/ml). Con A-stimulated AD-PBMC also
      showed significantly higher levels of IL-10 production than those from normal
      controls, although they were lower than the productions induced by HDM antigen.
      By contrast, the levels of IFN-gamma from AD PBMC stimulated with HDM or Con A,
      were significantly lower than those from normal controls. IFN-gamm production
      might be down-regulated by IL-10 in AD-PBMC. The overproduction of IL-10 seems to
      show that helper T type 2 (Th2) cells are rather dominantly activated than Th1
      cells and Th2 cells might contribute to produce the cytokines in response to HDM
      antigen in AD patients.

PMID- 9154697
TI  - [Comparative study of sustained-release in theophylline (Slobid, Theolong,
      Theodur) by pharmacokinetics].
AB  - We made a comparative study of three kinds of sustained-release of theophylline
      compounds by means of analysis of plasma concentrations. The drugs were Slobid
      (SB) (Up-john) 11 patients (10 men, 1 woman), Theolong (TL) (Eisai) 22 (10 men,
      12 women), Theodur (TD) (Nikken chemicals) 34 (18 men, 16 women), who were
      hospitalized from January 1989 to November 1994. These patients were given oral
      theophylline, bid at 9:00 and 21:00, plasma concentration of theophylline was
      determined at 9:00, 12:00, 15:00, 18:00 and 21:00, after plasma concentration
      reached a plateau. There were no significant differences as to the zero
      absorption rate, the moment absorption rate, clearance, but there were
      significant differences to the half life time (T1/2) of SB (18.9) > TL (13.5) >
      TD (10.1) (p = 0.0061), mean residence time (MRT) of SB (21.3 hr) > TL (16.7) >
      TD (15.2) (p = 0.0034), by measurements analysis of variance. These results
      suggest that these sustained-release drugs have different pharmacokinetics
      judging from the important indices including Cmax-Cmin, T1/2, V, MRT and Tml/2,
      and that the best one is the SB, the second is the TL, and the third is the TD
      for RTC therapy.

PMID- 9154699
TI  - [Enhanced lymphocyte proliferative response to house dust mite in the older but
      not in the younger asthmatic children].
AB  - Allergen-specific lymphocyte proliferation was measured by flow cytometry in 16
      children with atopic dermatitis (AD). 26 with bronchial asthma (BA) and 13 non
      atopic controls. Although the level of mite-S.I.F. (stimulation index measured by
      flow cytometry) in the younger AD children (2-7 y) was significantly higher than
      that in the non-atopic subjects (189.6 +/- 70.7 vs 113.9 +/- 11.0, p < 0.02),
      there was no elevation in the younger BA children (122.6 +/- 23.4). It is
      therefore likely that the elevated mite-S.I.F. level is related to the
      development of the allergic cellular inflammation representing the pathology of
      AD, rather than the IgE-mediated allergic reaction as a mechanism of childhood
      BA. Because the level of mite-specific IgE antibody in the younger BA children is
      elevated (93.6 +/- 41.2 PRU/ml), the result also indicates that mite-specific
      peripheral T lymphocytes do not play a critical role in stimulating the mite
      specific IgE synthesis. On the contrary, the older BA children (8-15 y) showed an
      elevated mite-S.I.F. level (176.0 +/- 54.6) significantly higher than that in the
      non-atopic subjects (114.6 +/- 13.9, p < 0.05) as well as that in the younger BA
      children (p < 0.05). Because other investigators have reported that the level of
      mite-specific lymphocyte proliferation is increased in the adult BA patients, the
      transition from childhood BA to adult-type BA may start at the age of about 8 y.

PMID- 9154700
TI  - [A case of bronchial asthma for whose status asthmaticus an anticholinergic drug
      was effective in weaning from inhaled anesthesia].

PMID- 9154701
TI  - 1st Congress of Pharmaceutical Sciences. Ribeirao Preto, Brazil, April 20-24,
      1997. Abstracts.

PMID- 9154702
TI  - Patient focus.

PMID- 9154703
TI  - The relative cost of different restorations in the UK.

PMID- 9154704
TI  - Dietary fluoride supplement dosage.

PMID- 9154705
TI  - Wish you were here.

PMID- 9154706
TI  - An index of implant treatment need.

PMID- 9154707
TI  - The future of dental amalgam: a review of the literature. Part 2: Mercury
      exposure in dental practice.
AB  - This is the second article in a series of seven on the future of dental amalgam.
      It describes the means of exposure to mercury which can occur in dental surgeries
      from the storage of mercury, preparation and placement of dental amalgam
      restorations, polishing dental amalgam restorations, the removal of amalgam
      fillings and the storage of waste amalgam. It also reports on the monitoring of
      dental practices and studies on the mercury air levels in dental surgeries and
      blood and urine levels in dentists and their staff. Also, studies which compare
      these levels with the health and neurobehaviour of dentists and their staff are
      included. In addition, it discusses post-mortem studies of the mercury levels in
      body organs in dentists and controls. It then recommends methods for the safe
      handling of mercury and dental amalgam. Finally, it discusses the issues
      surrounding the release of mercury into the environment from dental practices and
      industry.

PMID- 9154708
TI  - Complications and maintenance requirements of implant-supported prostheses
      provided in a UK dental hospital.
AB  - AIM: To assess the nature, timing and frequency of complications associated with
      implant therapy and to assess maintenance requirements of implant-supported
      prostheses. DESIGN: Retrospective analysis. SETTING: The Dental Hospital in
      Newcastle upon Tyne. METHOD: Dental records of 60 patients provided with implant
      supported prostheses were examined. Data were compiled on the number of fixtures
      placed per patient, the type of prosthesis provided, complications during the
      surgical and prosthodontic phases, and peri-implant soft tissue complications.
      RESULTS: 66 prostheses were placed on 236 fixtures over a 6-year period. Surgical
      complications included fixture loss (n = 6), dysaesthesia (n = 12), and the need
      for a guided tissue regeneration procedure (n = 10). Common maintenance
      requirements were tightening of components (n = 11), clip replacement (n = 7) and
      repair of conventional prostheses opposing implant supported prostheses (n = 7).
      Plaque control was unsatisfactory with almost half of the subjects requiring
      intensive oral hygiene instruction and scaling at the first post placement
      review. CONCLUSIONS: Prosthodontic maintenance requirements were high,
      particularly during the first year. Surgical complications were relatively
      infrequent. A case was made for a rigorous oral hygiene programme to reduce the
      potential for fixture loss through neglect. The financial cost associated with
      the maintenance of implant-supported prostheses should be incorporated in their
      overall funding.

PMID- 9154709
TI  - Sports supplement drinks and dental health in competitive swimmers and cyclists.
AB  - AIM: To assess dental status and sports supplement uptake in swimmers and
      cyclists. To determine chemico-physical properties of the most popular sports
      drinks. DESIGN: Descriptive, prevalence study of tooth wear and caries
      experience. Questionnaire analysis of sports drinks usage. SETTING: Two public
      swimming pools in Liverpool and three cycle clubs in North West England. SUBJECTS
      AND METHOD: A convenience sample of swimmers and cyclists was examined for caries
      and tooth wear. A questionnaire ascertained which sports drinks were consumed and
      their pattern of consumption. pH and titratable acidity, concentrations of
      calcium, phosphate and fluoride, and viscosity were analysed. Salivary flow rate
      in response to these drinks and water was also determined. RESULTS: 25 swimmers
      and 20 cyclists participated. Caries experience and tooth wear into dentine
      (excluding incisally exposed dentine) was significantly more frequent among
      cyclists (P < 0.05). Cyclists had significantly more upper palatal wear (P <
      0.001). Pattern of sport drink consumption between the two groups was
      significantly different (P < 0.001). pH range of the most popular sport drinks
      was 2.4-4.5. Salivary flow rate after a 1-minute rinse was significantly lower (P
      < 0.05) with one drink (0.47 ml/min) and water (0.41 ml/min) compared with the
      other drinks. CONCLUSIONS: An association between caries or erosive tooth wear
      and sport drink consumption was not found. However, the erosive potential of
      sport drinks is real and must be borne in mind as an aetiological factor for
      erosion in young people.

PMID- 9154710
TI  - Oral histoplasmosis associated with candidiasis in HIV-infected patients: a
      report of two cases.
AB  - Oral histoplasmosis, a rare condition, is reported in two HIV-infected patients.
      The lesions showed different characteristics. One was an ulcerative lesion
      presenting as the only manifestation of the disease. The other was nodular, with
      disseminated histoplasmosis. In both cases infection with Candida was also noted
      within the lesions.

PMID- 9154711
TI  - Complete dentures--the soft option. An update for general dental practice.
AB  - Permanent soft linings are frequently used as a 'soft option' blanket treatment
      for problems such as chronic pain under a lower denture, when it would be more
      appropriate to diagnose and eliminate any possible precipitating factors. The aim
      of this article is to provide an update on temporary and permanent soft materials
      and to give guidance on their indications and limitations of use, together with
      advice on their maintenance.

PMID- 9154712
TI  - Era-related changes in the Japanese cultural and social structure and conformist
      personality pathology--with a particular emphasis on borderline personality
      disorder.
AB  - We discussed relationship between the change of social structure and the specific
      conformist personality pathology, that is, Morita shinkeishitsu and borderline
      personality disorder. Morita shinkeishitsu that has been regarded as a basic
      pathology of broad range of neurosis is seldom seen in daily practice these days.
      On the other hand, borderline personality disorder that is a relatively new
      diagnostic domain is regarded as having a contemporary pathology, for example
      impulsivity, drug and sex abuse, and fragile interpersonal relationship. We
      consider that Morita shinkeshitsu corresponds to an industrialized society and
      that borderline personality disorder corresponds to a post industrialized
      (information based) society. This assumption should be leaded to the further
      discussion from a point of view of treatment.

PMID- 9154713
TI  - [The histologic study on chronological changes of bone trabeclae in human
      postnatal mandible].
AB  - The histologic study on chronological changes of human mandible was performed
      using 35 postnatal cases. The changes of bone density were divided into following
      2 stages. In cases of a 11 hours new born to 2 months (No. 13) baby, the bone
      density consisted of rather moderate parts that low. In cases of 2 months (No.
      14) baby to 66 years adult, it consisted of rather low parts than moderate parts.
      The changes of bone maturation were divided into next 2 stages. In cases of a 11
      hours new born to 3 months baby, the mandible consisted of woven-lamellar or
      lamellar bone. In cases of after 7 months baby to 66 years adult, it only
      consisted of lamellar bone. And then, the mandibular bone were exhibited manifold
      arrangements. The reticular arrangements were appeared locally in cases of a 11
      hours new born to 2 months baby but after 3 months, these were disappeared. The
      oblique and horizontal arrangements were appeared mainly in cases of a 11 hours
      new born to 7 months baby, and after 1 years old, not only these arrangements but
      also islet-like and vertical arrangements were appeared partially. After 40 years
      old, islet like arrangements were appeared remarkably. The bone resorption was
      noted at the whole mandible in a case of 3 months, and it extended larger in a
      case of 7 months. And after 1.1 years old, it was noted as same as 7 months.

PMID- 9154714
TI  - [Visually-guided discrimination and preference of sexuality in female macaque
      monkeys].
AB  - Visual information about face and body including facial expression and bodily
      behavioral patterns has been known to play an important role in social and
      emotional communication in monkeys. Its involvement in sexual activity has also
      been demonstrated in male monkeys but it is poorly understood in female monkeys.
      In the present study, visually-guided discrimination and preference of sexuality
      were investigated in female macaque monkeys performing operant bar-press tasks in
      an experimental cage which had a transparent panel facing a display. In the sex
      discrimination task, two rhesus monkeys (Macaca mulatta) were trained to
      discriminate sex of a monkey shown in a picture which was randomly selected from
      six photographs (three males and three females) and was presented on the display.
      The monkey pressed a right or left bar for male or female monkey, respectively,
      to get water as a reward. Under this discrimination task, the monkeys could
      discriminate the sexes of monkeys shown in newly presented pictures. When choice
      bars were reversed, correct responses significantly decreased below chance level.
      In the sex preference task, three rhesus monkeys and three Japanese monkeys (M.
      juscata) were used. The monkeys voluntarily pressed the bar to watch the video
      movie showing either male or female rhesus monkeys. The movies were presented as
      long as the subject kept pressing the bar. The same movie was continued when the
      monkey pressed the bar again within 10s after the previous release of the bar,
      while it was changed to the other when 10s passed after the subject released the
      bar. The total duration of the responses in daily sessions was measured. In this
      visual preference task, four out of six monkeys showed sex preference. Three
      adult Japanese monkeys (6-8 y) pressed the bar to watch the video movie of male
      monkeys which was taken in breeding season with longer duration than that of
      female monkeys taken in the same season. The other two adult rhesus monkeys (7 8
      y) did not show the sexual preference. The one remaining youngest rhesus monkey
      (5 y) preferred to watch the female movie which was taken in non-breeding season.
      The visual preference was observed not only in winter but also in summer when
      tested. The present results suggest that visual information alone is sufficient
      to discriminate sex and produce sex preference in some female monkeys. The
      seasonal changes in visual appearance of objects seem to be more determinant
      factors for the preference than the endogenous factors of subjects.

PMID- 9154715
TI  - [Analysis of the swimming pattern and the velocity of bacteria using video
      tracking method].
AB  - The swimming patterns and the velocities of several flagellated bacteria were
      measured by a computer assisted video tracking method. The moving path of the
      individual bacterium revealed that the bacterium frequently changed its swimming
      direction and velocity. The velocity among bacterial strains varies widely. In
      low viscous environment. Campylobacter jejuni has characteristic swimming pattern
      with frequent changes in their swimming direction. As the viscosity increase, C.
      jejuni increases its velocity at a little higher viscosity of 3 centipoise (cP)
      and secondly increases at about 40 cP. Different from other flagellated bacteria,
      the swimming pattern of C. jejuni in these two velocity peaks were changed. C.
      jejuni exhibited continuously forward moving path in the first peak, but in the
      second it repeated back and forth swimming pattern. We thus assumed that C.
      jejuni may use a different swimming mode in high viscous media from the original
      mode mediated by the propelling force of the flagella. This method is useful for
      a detail analysis of bacterial movement and moving patterns in different
      environmental conditions.

PMID- 9154716
TI  - [An old female case of vero-cytotoxin-producing Escherichia coli O-157: H7
      infection].
AB  - It is well known that verocytotoxin-producing Escherichia coli O-157 : H7
      infection can be severe in elderly persons. We report an 82-year-old female case
      of verocytotoxin-producing Escherichia coli O-157 : H7 infection. She was
      admitted to our hospital because of bloody diarrhea. The hemolytic-uremic
      syndrome (HUS) was not occurred, but systemic edema, ascites, pleural effusion
      and pulmonary edema with hypoxyemia gradually appeared. Treatment with human
      immunoglobulin in addition to fluid therapy, antibiotics, diuretics and human
      serum albumin resulted in dramatic improvement. Management of complications such
      as sepsis and electrolyte disturbance caused by this infection was considered to
      be important in elderly patients.

PMID- 9154717
TI  - [Ovarian cancer in Israel, 1960-1989].
AB  - In Israel ovarian cancer ranks among the most common malignant diseases in women.
      It is also one of the main causes of death from cancer in females in this
      country. Our population is composed of immigrants from diverse social, cultural,
      and geographical backgrounds, and only a sector of the inhabitants, mainly the
      younger generation, is Israeli-born. This study evaluates the trends of
      epidemiological and clinical data on ovarian cancer during 3 decades, 1960-1989,
      and includes a total of 5,786 cases of ovarian cancer. Information was obtained
      from the Central Israel Cancer Registry of the Ministry of Health and from the
      Central Bureau of Statistics. The incidence was stable during the survey period
      and was about 15-17/100,000 in women over the age of 15. Most (90%) were
      diagnosed over the age of 40. In women of European/American origin the incidence
      of ovarian cancer is 3 times greater than in women of Asian/African origin. The
      rate in the Israeli-born is between those of the other 2 groups, but closer to
      that of the European/American group. Over 70% were diagnosed with advanced
      disease (stage III-IV). Prognosis improved during the period of the study: 5-year
      survival was 19% in the early 60's and 31% in the 80's. During the last decade of
      the survey improvement was mainly in 2-year survival (from 38.5% to 60%).

PMID- 9154718
TI  - [Evidence for casual household transmission of HIV: review and analysis].
AB  - All reported case-studies in which the author-described route of infection was
      deemed to be casual household contact were reviewed and analyzed, as well as all
      sample-based studies designed to estimate the frequency of casual household
      transmission. Several recurring biased mechanisms of interpretation were found in
      the studies, the use of which made it impossible to obtain evidence for casual
      household transmission. After correcting for these interpretations 8 documented
      cases of casual household transmission were found. Analysis of the sample-based
      studies indicated 10 cases of casual household transmission, which occurs at a
      risk of 0.4% per year of contact (95% confidence interval: 0.20 to 0.66).

PMID- 9154719
TI  - [Drinking and driving].
AB  - A worrisome connection between driving and drinking was found in 166 people
      randomly surveyed in public places in Beer Sheba. 80% of the study population
      stated that they drink alcoholic beverages. Of these, 45% reported drinking at
      least once a week, and 21% drank 3 glasses/cans at each drinking bout. We noted a
      trend among those who drank frequently to drink greater amounts. Of the sample,
      110 interviewees stated that they had a driver's license and that they drank
      alcoholic drinks. 39% reported driving after a number of alcoholic drinks, and
      23% of them did so invariably or frequently. 5% drank while driving. The drinkers
      exhibited a high-risk behavioral pattern, remaining in the car with friends (53%)
      or relatives (16%) also under the influence of alcohol. Those who are aware of
      the influence of alcohol on their driving skills and the danger of being involved
      in car accidents, moderate their consumption of alcohol. The results of the study
      confirm our hypothesis that there is an upswing in the phenomenon of high-risk
      driving connected with drinking alcoholic beverages.

PMID- 9154720
TI  - [On the value of the placebo: reflections on homeopathy].
AB  - A case is presented in which homeopathic "treatment" helped, despite the fact
      that the patient did not take the medication. The author surveys research which
      has been conducted on homeopathy and concludes that its benefits derive from non
      specific influences of the healer upon the patient, similar to a placebo effect.
      The importance of this influence is stressed, and its wider application in
      conventional medicine is urged.

PMID- 9154721
TI  - [An in-hospital pain service: present activity and future trends].
AB  - Although significant progress has been made in the past 2 decades in our
      understanding of pain pathophysiology and in the development of new analgesic
      drugs and techniques, many patients still experience considerable pain during
      hospitalization. Unrelieved pain is common not only among patients undergoing
      surgery, but also in those with a variety of other medical problems. These
      findings led to the development of our in-hospital acute pain service. This in
      hospital pain service has been active since the late eighties, treating both
      postoperative pain and non-surgical pain in hospitalized patients. During 1995,
      2140 patients were treated totaling 8717 treatment days in 18 different medical
      units and departments. Overall success was more than 75%. We review our
      experience in treating in-patients who suffer from pain and discuss future trends
      and need for such a specialized service.

PMID- 9154722
TI  - [Typhlitis].
AB  - Typhlitis (from Greek, "typhlon", cecum) is an inflammatory process involving the
      cecum and ascending colon--in neutropenic patients after chemotherapy. Early
      diagnosis and treatment is of great importance, since the mortality is high. In
      the past decade there has been an increasing number of reports, as well as
      impressive improvement in diagnosis, and treatment. We describe 2 patients
      treated in our department. We emphasize the evolving changes in the management of
      these patients, from early surgical intervention to conservative treatment, and
      the problem of prophylactic treatment for those who survive an episode of
      typhlitis.

PMID- 9154723
TI  - [Diverticular disease of the appendix].
AB  - The incidence of appendiceal diverticulosis in pathologic specimens is 0.004
      2.1%. Diverticular disease of the appendix is classified as congenital (true) or
      acquired (false). The clinical presentation differs from that of acute
      appendicitis. The average age is older, the pain is often intermittent, and while
      localized in the right lower abdominal quadrant, is of longer duration. No
      further treatment besides appendectomy is needed. Since a high rate of
      perforations, peritonitis and lower gastrointestinal bleeding have been reported
      as complications, it is recommended that in those with an incidental finding of
      diverticula of the appendix during surgery, that appendectomy be performed. It is
      not recommended to perform prophylactic appendectomy when diverticula of the
      appendix are found on barium enema.

PMID- 9154724
TI  - [Physicians and the battle against road accidents].

PMID- 9154725
TI  - [Nobel Prize winners in physiology and medicine--1996].

PMID- 9154727
TI  - [Health education--is it worth it?].

PMID- 9154726
TI  - [Bacteriocins of lactic acid bacteria--characteristics and mode of action].

PMID- 9154728
TI  - [Fetal macrosomia: diagnosis and management in labor].

PMID- 9154729
TI  - [Shoulder dystocia: the obstetrician's nightmare].

PMID- 9154730
TI  - [Directions in the diagnosis and management of acute myocardial infarction:
      update].

PMID- 9154731
TI  - [Energy requirements of the burned patient].

PMID- 9154732
TI  - [Calcium channel blockers scare].

PMID- 9154733
TI  - [Relative significance of clinical examinations, imaging techniques and EMG].

PMID- 9154734
TI  - [Degenerative lumbar spondylolisthesis].

PMID- 9154735
TI  - [Blunt perineal injuries].
AB  - Blunt perineal and anal injuries are rare. We describe 2 patients who suffered
      injury to the perineum and anal canal due to blunt force. New surgical techniques
      for the reconstruction of the sphincteric mechanism are promising and should be
      used by the initial treating surgeon as minimal procedures in the perineal
      region. Anal tagging, minimal debridement, approximation of the edges of perineal
      laceration, repeated irrigation and loop-colostomy for fecal diversion should be
      the only initial surgical procedures.

PMID- 9154736
TI  - Cartesian optics and the mastery of nature.
AB  - Descartes's Dioptrics is more than a mere technical treatise on optics; it is an
      essay in the "practical philosophy" that he claimed could render us "masters and
      possessors of nature." Descartes's practical intent is indicated first by the
      instrumentalist character of his derivation of the sine law of refraction, which
      is based on a heuristic and readily mathematizable model that requires no
      consideration of light's "true nature." Descartes's subsequent discussion of
      human vision is an extended critique of nature's workmanship that grounds the
      possibility of improving vision by artificial means. I suggest that this critique
      is the source of Descartes's doctrine that the purpose of sensory perception is
      to preserve the mind-body composite, not to provide knowledge of the essential
      nature of things. Accordingly, the ultimate goal of the Dioptrics is to "master"
      human vision by raising it from a mere means of self-preservation to an
      instrument of scientific knowledge.

PMID- 9154737
TI  - LSD before Leary. Sidney Cohen's critique of 1950s psychedelic drug research.
AB  - In 1962 Sidney Cohen presented the medical community with its first warning about
      the dangers of the drug LSD. LSD had arrived in the United States in 1949 and was
      originally perceived as a psychotomimetic capable of producing a model psychosis.
      But in the mid 1950s intellectuals in Southern California redefined LSD as a
      psychedelic capable of producing mystical enlightenment. Though LSD was an
      investigational drug, authorized only for experimental use, by the late 1950s
      psychiatrists and psychologists were administering it to cure neuroses and
      alcoholism and to enhance creativity. Cohen's 1960 study of LSD effects concluded
      that the drug was safe if given in a supervised medical setting, but by 1962 his
      concern about popularization, nonmedical use, black market LSD, and patients
      harmed by the drug led him to warn that the spread of LSD was dangerous. The
      subsequent government crackdown and regulation of LSD preceded the 1960s drug
      movement and was prompted by medical, not social, concerns.

PMID- 9154738
TI  - Mnemonics suggested for DSM-IV diagnostic criteria.

PMID- 9154739
TI  - Establishment of behavioral parameters for the evaluation of osteopathic
      treatment principles in a rat model of arthritis.
AB  - Unilateral arthritis was produced in rats by use of methylated bovine serum
      albumin in a model of antigen-induced arthritis. The progression of arthritis was
      measured by computerized motion analysis, bilateral joint circumference,
      voluntary extension force of the hindlegs, and length of ankle extension. Animals
      with induced arthritis were assigned to treated and untreated groups on the basis
      of approximately equal deficits by the parameters measured. A third group of
      rats, which did not have arthritis induced and received no treatment, served to
      establish mean normal parameters. Modified techniques of muscle energy, passive
      movement of the ankle and knee, and passive myofascial stretch were applied to
      the animals, and the animals were exercised in a mechanized exercise wheel.
      Parameters associated with gait were examined by computerized motion analysis of
      walking. Animals treated with manipulation and exercise improved significantly
      relative to untreated animals with antigen-induced arthritis in vertical ankle
      lift, ankle-based and foot-based stride lengths, knee circumference, and
      normalized extension of the ankle. The results demonstrate that the parameters
      identified can be used to detect functional deficits and significant improvement
      from those deficits can be derived from a nonpharmacologic treatment paradigm
      that includes osteopathic manipulation and exercise in an animal model of
      arthritis. These parameters may be useful in the identification of the relative
      benefits of independent treatment variables including frequency of osteopathic
      manipulation and exercise and the relative benefits of each in this model. Also,
      they may elucidate how these treatments produce their beneficial effects
      clinically.

PMID- 9154740
TI  - Martial arts injuries.
AB  - In the United States, approximately 1.5 million to 2 million persons practice the
      martial arts. It is the general belief that martial arts are safe, with little
      thought given to the physical forces involved. Some enthusiasts gravitate to the
      martial arts to learn self-defense, whereas others participate to improve
      cardiovascular fitness, flexibility, and self-esteem. Some join for the
      structured exercise programs, whereas others desire the artistic expression or
      have a need to compete. Injuries involve the head and neck region, trunk, and
      extremities. Soft tissue trauma, hematomas, and lacerations are some of the most
      common injuries. Occasionally fractures occur, most often involving the hands and
      digits. The neurosurgical literature indicates that wearing headgear increases
      the shearing injury to nerve fibers and neurons in the brain in proportion to the
      degree of acceleration to the head. Three case presentations illustrate death
      resulting from anterior chest trauma.

PMID- 9154741
TI  - Revisiting epiglottitis: a protocol--the value of lateral neck radiographs.
AB  - A retrospective review was done on the medical records (March 1986 through
      December 1989) of patients referred to Pittsburgh Children's Hospital with the
      presumptive diagnosis of epiglottitis. Data obtained included age, final
      diagnosis, referring physician's radiographic evaluation/interpretation,
      procedures (intubation, IV administered, aerosol, cultures obtained), transport
      times, and long-term morbidity and mortality. The diagnostic value of lateral
      neck radiographs was analyzed. Lateral neck radiographs were found to be of
      little value in the primary evaluation of epiglottitis. Rather, skilled
      personnel, using an established protocol, did limit morbidity and mortality in
      patients with symptoms consistent with epiglottitis. All medical centers should
      develop a protocol for management of patients presenting with symptoms suggestive
      of epiglottitis.

PMID- 9154742
TI  - Anorexia nervosa presenting as a somatic delusional disorder responsive to
      pharmacotherapy.
AB  - A case of somatic delusional disorder with a severe secondary eating disorder is
      described. The patient's psychotic symptoms and emaciation were markedly improved
      with separate trials of antipsychotic and antiobsessional medications. Further
      epidemiologic studies of eating disorders with coexisting psychotic disorders are
      suggested. Classification of eating disorders to include a subset with psychotic
      or obsessional features (or both) may prove useful in future diagnoses.
      Pharmacotherapy may be a beneficial therapeutic modality in treating eating
      disorders with concurrent psychotic features.

PMID- 9154743
TI  - Common bile duct injury after laparoscopic cholecystectomy: report of two cases.
AB  - With a few exceptions, laparoscopic cholecystectomy has rapidly supplanted open
      cholecystectomy as the operation of choice for symptomatic cholelithiasis. The
      risk of bile duct injury using the laparoscopic technique is almost twice that of
      the open technique (0% to 1% vs 0% to 0.5%). There appears to be a direct
      correlation between the number of cases an individual surgeon performs and the
      frequency of bile duct injury. The nature of bile duct injuries following the
      laparoscopic technique tends to be more serious than those seen following the
      open procedure. In addition, more than 50% of bile duct injuries go undetected at
      the time of operation. A number of technical steps can be taken to help prevent
      bile duct injuries when using the laparoscopic technique. This article reports
      two such cases to alert the surgeon that a high index of suspicion must always be
      maintained concerning the possibility of bile duct injury following laparoscopic
      cholecystectomy.

PMID- 9154744
TI  - Delayed cardiac tamponade following a stab wound: a case report.
AB  - Penetrating trauma is a frequent presentation to urban emergency departments
      (EDs). Pericardial effusion with cardiac tamponade is a possible complication of
      penetrating trauma to the chest, to the back, and to the upper abdomen. Even if
      patients are stable initially without signs or symptoms of cardiac tamponade,
      there can be delayed sequelae. Presented is a case of cardiac tamponade diagnosed
      21 days after a stab wound to the epigastrium.

PMID- 9154745
TI  - ECG and cardiac enzymes changes associated with subarachnoid hemorrhage.

PMID- 9154746
TI  - Methyl parathion facts: a physician resource.

PMID- 9154747
TI  - ECG of the month. Group beating. Atrial and ventricular premature impulses.

PMID- 9154748
TI  - Allergic diagnosis: skin testing and rast.
AB  - In a minority of patients with allergic rhinitis, diagnosis of the offending
      allergens is necessary for control of symptoms. Skin endpoint titration (SET)
      testing, the most advanced form of skin testing, and the radioallergosorbent test
      (RAST) are the only two diagnostic tests that give quantitative results upon
      which to base immunotherapy. Patients who undergo diagnostic testing must
      understand the commitment involved in a program of immunotherapy. This review
      hopes to enable clinicians to better understand the techniques of skin testing
      and RAST and how and when these tests may be of use to their patients suffering
      from allergic rhinitis.

PMID- 9154749
TI  - Radiology case of the month. Sudden onset of shortness of breath. Sarcoidosis,
      complicated by acute pneumothorax.

PMID- 9154750
TI  - The journal 100 & 150 years ago. The bizarre diseases and deaths of American
      Presidents. Part I.

PMID- 9154751
TI  - Liability issues in managed care.
AB  - The explosive growth in Managed Care Organizations as a mechanism for providing
      health care in the United States has generated an equal explosion in litigation
      and new legislation related to problems within this delivery system. Abuses have
      included the "gagging" of physicians from providing full disclosure of medical
      options for their patients, inappropriate denial of care, denial of specialty
      referral, false claims data, insurer insolvency, economic credentialling,
      deselection, financial disincentives to render care, and lack of appeal or
      grievance mechanisms. These issues and others have resulted in injuries to
      patients and damage to the patient/physician relationship. This article discusses
      some of the more dramatic litigated cases and endeavors to alert both physicians
      and patients to potential legal matters that should be considered before becoming
      involved within this structure.

PMID- 9154752
TI  - The American Heart Association. Focus on public advocacy issues.
AB  - The American Heart Association is a large volunteer organization whose mission is
      to reduce disability and death due to heart disease and stroke. However, working
      in isolation, the Association has limited potential to achieve its goals. We must
      work as individuals, as an organization, and in coalition with other
      organizations to direct major public policy issues. Only in this way can we bring
      about substantial change on a national level. Some public advocacy
      accomplishments, and major priorities for the present and future, are reviewed.
      Readers are invited to lend their support.

PMID- 9154753
TI  - Cardiovascular research support by the American Heart Association in Louisiana.
AB  - The American Heart Association (AHA) was founded in 1924 by a group of physician
      scientists to promote the exchange of research ideas in an era when the treatment
      of heart disease was extremely frustrating. The organization has evolved to
      include education and community service in its mission, but the support and
      promotion of quality research has remained at the AHA's core. Research support by
      the AHA has been responsible for major advances in cardiovascular medicine,
      including the development of diuretics, pacemakers, artificial heart valves,
      defibrillators, cardiopulmonary resuscitation, hypercholesterolemia therapy, and
      artificial surfactant. Working to ensure the efficient distribution of funds, the
      AHA has distributed nearly $1.4 billion in support of quality research for
      graduate and medical students, post-doctoral fellows, and beginning and
      established investigators. Such support has assisted in the career development of
      four Nobel Prize winners. While cardiovascular disease remains America's leading
      cause of death, the activities of the AHA continue to support advances in its
      diagnosis and treatment.

PMID- 9154754
TI  - The American Heart Association and emergency cardiac care training in Louisiana-
      past, present, and future.

PMID- 9154755
TI  - Update on American Heart Association education and information initiatives.
AB  - The American Heart Association has placed emphasis on providing information and
      educational resources about cardiovascular diseases and stroke. These initiatives
      are helping to reach a broad-based population of those at risk and potentially at
      risk. Programs include employee health, supplements for health education in
      schools, and community-focused programs for awareness and modification of
      cardiovascular risk factors. Healthcare professionals are encouraged to increase
      their knowledge of these resources to better serve their patients.

PMID- 9154756
TI  - Application of Dall-Miles cable grip system for transtrochanteric osteotomy.
AB  - We have applied the Dall-Miles cable grip system for fixation in 15 cases of a
      transtrochanteric valgus osteotomy for osteoarthritis. After three phases of
      modification, we could achieve stable fixation for the three fragments of the
      greater trochanter, proximal and distal femur using only one set of this system
      and could prevent migration and over-traction of the abductor muscles by this
      way.

PMID- 9154757
TI  - The vascular function of the long-term coronary artery after Kawasaki disease-
      evaluation by intracoronary injection of acetylcholine.
AB  - The vascular function of the coronary arteries in children after Kawasaki disease
      (KD) as yet remains uncertain. Here we report our findings of the vascular
      response of the coronary arteries after intracoronary injection of acetylcholine
      in patients after KD. A total of 29 patients, 19 after KD and 10 as control, were
      examined using coronary angiography (CAG). These were divided into 4 groups
      according to the type of the coronary artery lesions: Group 1 consisted of those
      with regressed aneurysms and involved 29 sites. These aneurysms had developed in
      the acute stage and had subsequently regressed and demonstrated normal findings
      in follow-up CAG. Group 2 consisted of those with persistent aneurysms involved
      30 sites. Group 3 involved 52 angiographically normal sites in patients after KD.
      And Group 4 consisted of control patients and involved 70 sites. These patients
      had congenital heart disease with normal coronary arteries. During CAG we infused
      15 micrograms acetylcholine chloride into the right or left coronary artery. The
      luminal diameters were measured using a cine-videodensitometric analyser to study
      the distensibility of the coronary artery wall. The change in the diameter was an
      increase of 13.71% +/- 15.09% (mean +/- SD) in the normal KD Group 3, and 12.21%
      +/- 13.83% in the control Group 4, demonstrating marked vasodilatation. In
      contrast, the change in the regressed aneurysms Group 1, and in the persistent
      aneurysms Group 2, was -2.65% +/- 16.65%, and -0.08% +/- 6.51%, respectively,
      demonstrating no change or mild vasoconstriction. The change in Group 1, and in
      Group 2, was less than in normal Group 3 or control Group 4. The normal Group 3
      showed no significant difference from control Group 4. These findings suggested
      that the coronary artery with regressed aneurysms, or with persistent aneurysms
      after KD has impaired vascular function and is therefore at risk for developing
      to atherosclerosis in the long-term.

PMID- 9154758
TI  - Optimal timing of a second-look operation for advanced epithelial ovarian cancer.
AB  - To clarify the optimal timing of second look operation (SLO) for advanced ovarian
      cancer, we retrospectively reviewed the records of 53 patients with FIGO stage 2,
      3 and 4 epithelial ovarian cancer. SLOs were performed more than 12 months after
      primary surgery in 35 patients (late SLOs), and immediately after first-line
      chemotherapy in 18 patients (early SLOs). We examined data on SLO findings and
      patients' clinical courses. SLO findings were positive 5 (27.7%) of 18 in the
      early SLO group and in 11 (31.4%) of 35 in late SLO group. Positive findings were
      detected by washing cytology in 3 (60%) of the 5 in the early SLO group compared
      with 2 (18.2%) of the 11 in the late SLO group. Patients with microscopic disease
      had better prognosis than patients with macro lesions. False-negative SLO
      findings were 30.8% in the early SLO group and 12.5% in the late SLO group. All
      patients who recurred after negative SLOs had grade 2 and 3 tumors. The benefits
      of SLO were limited to accurate evaluation of first-line chemotherapy and early
      detection of persistent disease. In these implications, early performance of SLO
      is recommended.

PMID- 9154759
TI  - Characterization of cytotoxic T lymphocytes recognizing autologous tumor cells
      with plural HLA-class I alleles in a patient with esophageal cancer.
AB  - T cell sublines and clones were established from the parental HLA-A2601
      restricted cytotoxic T lymphocyte line (KE-4 CTL, HLA-A2601/2402, -B5101/40012, 
      Cw0102/0302) to investigate their capability to recognize tumor antigens on HLA
      class I alleles other than HLA-A2601. Thirty-nine of 52 (75%) sublines or 30 of
      83 (36%) clones produced interferon (IFN)-gamma by recognition of the autologous
      KE-4 tumor cells. Among these 39 CTL sublines, 22, 22, and 2 sublines produced
      IFN-gamma by recognition of HLA-A2402+, -B5101+, and Cw0102+ allogenic tumor
      cells, respectively. Four, 8, and 4 of these 30 CTL clones also produced IFN
      gamma by recognition of HLA-A2402+, -B5101+, and Cw0102+ allogenic tumor cells,
      respectively. The other 13 sublines or 53 clones failed to produce IFN-gamma by
      recognition of the autologous tumor cells, respectively. These results suggest
      the presence of CTL recognizing shared tumor antigens on autologous tumor cells
      expressed by plural HLA-class I alleles in a patient with esophageal SCC.

PMID- 9154760
TI  - Neurokinin-1 (NK1) receptors mediate tachykinin-induced depression of GABA
      current in bullfrog sensory neurons.
AB  - Receptors responsible for the tachykinin-induced depression of gamma-aminobutyric
      acid-A (GABAA) receptors in neurons of bullfrog dorsal root ganglia (DRG) were
      investigated by using whole-cell voltage-clamp techniques. Substance P (10 nM-1
      microM) depressed the inward current produced by GABA (GABA current) in a
      concentration-dependent manner. Substance P did not change the reversal potential
      of the GABA current. Neurokinin A also depressed the GABA current with potency
      similar to those of substance P. [D-Arg1, D-Trp7,9, Leu11]substance P (spantide,
      1 microM) shifted the concentration-inhibition curve of substance P to the right.
      Spantide (1 microM) increased the IC50 from 56 nM to 210 nM. Lineweaver-Burk
      plot, a reciprocal plot of the concentration-inhibition curve, showed that
      spantide did not change the maximum response (Vmax) to substance P but increased
      the apparent dissociation constant (Kd). CP99994 (1 microM), an neurokinin-1
      (NK1) receptor antagonist, inhibited the substance P-induced depression of the
      GABA current. These results suggest that the tachykinin-induced depression of the
      GABAA receptor sensitivity is mediated by NK1 receptors in neurons of bullfrog
      DRG.

PMID- 9154761
TI  - Detection of MAGE-1 tumor antigen in brain tumor.
AB  - The expression of MAGE tumor rejection antigens in brain tumors is unclear. We
      investigated the expression of MAGE-1 and -4 proteins in brain tumors with
      antibodies to recombinant MAGE-1 and -4 proteins. MAGE-1 or -4 protein was
      detected in a majority (12 of 14) or some (5 of 14) of gliomas, respectively, by
      the immunoblot analysis. In contrast, MAGE-1 or -4 protein was rarely detected in
      the non-glioma tumors (3 of 14 or 1 of 14, respectively). Cellular MAGE-1 protein
      was detected in the cytoplasma of the glioblastoma cells with immunohistochemical
      staining. The expression of the MAGE-4 protein was confirmed by enzyme-linked
      immunosorbent assay. The results suggest that the MAGE-1 protein is an
      appropriate target molecule for specific immunotherapy of glioma.

PMID- 9154763
TI  - A case of zoster in the 2nd and 3rd branches of the trigeminal nerve associated
      with simultaneous herpes labialis infection--a case report.
AB  - A patient with herpes zoster infection affecting the second and third branches of
      the trigeminal nerve is reported. This case demonstrates the occurrence of a
      simultaneous VZV and HSV infection. Isolation of these viruses from exudates of
      the blisters was required to prove coexistence of the two viruses within the same
      blister. Relevant literature is discussed.

PMID- 9154762
TI  - A case of malignant lymphoma with hemophagocytic syndrome presenting as hepatic
      failure.
AB  - We report the case of a 50-year-old female with malignant lymphoma presenting
      hemophagocytic syndrome and liver failure. She developed high fever, marked
      jaundice, and progressive liver failure, followed by evidence of disseminated
      intravascular coagulation (DIC). The course was complicated by severe hepatitis
      and the patient died six days after admission. Pathological diagnosis on autopsy
      specimens of the lung hilar lymph nodes was non-Hodgkin's T cell lymphoma, of the
      diffuse small cell type. Histopathologic examination of the liver demonstrated
      diffuse liver cell destruction with prominent T lymphocyte infiltration in the
      portal and periportal area. In addition to marked lymphoma cell infiltration,
      hemophagocytosis by prominent infiltrative macrophages was observed in various
      organs, such as the liver and bone marrow, indicating the hemophagocytic
      syndrome. The hemophagocytic syndrome characterized in the present case may have
      been responsible for the extremely rapid and fulminant course.

PMID- 9154764
TI  - Squamous cell carcinoma of the endometrium with human papillomavirus type 31.

PMID- 9154765
TI  - Interference with cardiac pacemakers by cellular telephones.
AB  - BACKGROUND: A growing body of evidence suggests that electromagnetic interference
      may occur between cardiac pacemakers and wireless hand-held (cellular)
      telephones, posing a potential public health problem. Electromagnetic
      interference may occur when the pacemaker is exposed to an electromagnetic field
      generated by the cellular telephone. METHODS: In this multicenter, prospective,
      crossover study, we tested 980 patients with cardiac pacemakers with five types
      of telephones (one analogue and four digital) to assess the potential for
      interference. Telephones were tested in a test mode and were programmed to
      transmit at the maximal power, simulating the worst-case scenario; in addition,
      one telephone was tested during actual transmission to simulate actual use.
      Patients were electrocardiographically monitored while the telephones were tested
      at the ipsilateral ear and in a series of maneuvers directly over the pacemaker.
      Interference was classified according to the type and clinical significance of
      the effect. RESULTS: The incidence of any type of interference was 20 percent in
      the 5533 tests, and the incidence of symptoms was 7.2 percent. The incidence of
      clinically significant interference was 6.6 percent. There was no clinically
      significant interference when the telephone was placed in the normal position
      over the ear. Interference that was definitely clinically significant occurred in
      only 1.7 percent of tests, and only when the telephone was held over the
      pacemaker. Interference was more frequent with dual-chamber pacemakers (25.3
      percent) than with single-chamber pacemakers (6.8 percent, P<0.001) and more
      frequent with pacemakers without feed-through filters (28.9 to 55.8 percent) than
      with those with such filters (0.4 to 0.8 percent, P=0.01). CONCLUSIONS: Cellular
      telephones can interfere with the function of implanted cardiac pacemakers.
      However, when telephones are placed over the ear, the normal position, this
      interference does not pose a health risk.

PMID- 9154766
TI  - Measurements of serum mullerian inhibiting substance in the evaluation of
      children with nonpalpable gonads.
AB  - BACKGROUND: Mullerian inhibiting substance, produced constitutively by the
      prepubertal testes, promotes involution of the mullerian ducts during normal male
      sexual differentiation. In children with virilization and nonpalpable gonads,
      only those with testicular tissue should have detectable serum concentrations of
      mullerian inhibiting substance. METHODS: We measured serum mullerian inhibiting
      substance in 65 children with virilization at birth and nonpalpable gonads (age
      at diagnosis, 2 days to 11 years) and serum testosterone in 54 of them either
      after the administration of human chorionic gonadotropin or during the
      physiologic rise in testosterone that occurs in normal infants. RESULTS: The mean
      (+/-SD) serum mullerian inhibiting substance concentration in the 17 children
      with no testicular tissue was 0.7+/-0.5 ng per milliliter, as compared with
      37.5+/-39.6 ng per milliliter in the 48 children with testes (P<0.001). In the
      latter group, the mean values in the 14 children with abnormal testes and the 34
      with normal testes were 11.5+/-11.8 and 48.2+/-42.1 ng per milliliter,
      respectively (P< 0.001). The sensitivity and specificity of the serum mullerian
      inhibiting substance assay for detecting the absence of testicular tissue were 92
      percent and 98 percent, respectively, as compared with 69 percent and 83 percent
      for the measurement of serum testosterone. Furthermore, measurement of serum
      mullerian inhibiting substance was more sensitive than serum testosterone
      measurement for the identification of children with abnormal testes (67 percent
      vs. 25 percent), whereas the specificity of the two tests was similar.
      CONCLUSIONS: Measurements of serum mullerian inhibiting substance can be used to
      determine testicular status in prepubertal children with nonpalpable gonads, thus
      differentiating anorchia from undescended testes in boys with bilateral
      cryptorchidism and serving as a measure of testicular integrity in children with
      intersexual anomalies.

PMID- 9154767
TI  - Thalidomide for the treatment of oral aphthous ulcers in patients with human
      immunodeficiency virus infection. National Institute of Allergy and Infectious
      Diseases AIDS Clinical Trials Group.
AB  - BACKGROUND: In patients with advanced human immunodeficiency virus (HIV)
      infection, aphthous ulceration of the mouth and oropharynx can become extensive
      and debilitating. Preliminary reports suggest that thalidomide may promote the
      healing of oral aphthous ulcers. METHODS: We performed a double-blind,
      randomized, placebo-controlled study of thalidomide as therapy for oral aphthous
      ulcers in HIV-infected patients. The patients received a four-week course of
      either 200 mg of thalidomide or placebo orally once per day. They were evaluated
      weekly for the condition of the ulcers, their quality of life, and evidence of
      toxicity. Assays were performed for plasma tumor necrosis factor alpha (TNF
      alpha), soluble TNF-alpha receptors, and HIV RNA. RESULTS: Sixteen of 29 patients
      in the thalidomide group (55 percent) had complete healing of their aphthous
      ulcers after four weeks, as compared with only 2 of 28 patients in the placebo
      group (7 percent; odds ratio, 15; 95 percent confidence interval after adjustment
      for group sequential testing, 1.8 to 499; unadjusted P<0.001). Pain diminished
      and ability to eat improved with thalidomide treatment. The adverse effects noted
      with thalidomide included somnolence and rash (7 patients each), and 6 of the 29
      patients discontinued treatment because of toxicity. Thalidomide treatment
      increased HIV RNA levels (median increase, 0.42 log10 copies per milliliter;
      increase with placebo, 0.05; P=0.04). With thalidomide treatment there were
      unexpected increases in the plasma concentrations of TNF-alpha and soluble TNF
      alpha receptors. CONCLUSIONS: Thalidomide is an effective treatment for aphthous
      ulceration of the mouth and oropharynx in patients with HIV infection.

PMID- 9154768
TI  - High-dose intravenous immune globulin and the response to splenectomy in patients
      with idiopathic thrombocytopenic purpura.
AB  - BACKGROUND: High-dose intravenous immune globulin produces a temporary rise in
      the platelet count in patients with idiopathic thrombocytopenic purpura.
      Splenectomy may also be effective, but it is not possible to predict which
      patients will have a good response. We hypothesized that the response to
      intravenous immune globulin predicts the response to splenectomy. METHODS: We
      studied retrospectively 30 patients with idiopathic thrombocytopenic purpura who
      had first been treated with immune globulin and then undergone splenectomy. The
      responses to the two treatments were classified on the basis of the platelet
      count as poor (<50,000 per cubic millimeter), good (50,000 to 150,000 per cubic
      millimeter), or excellent (>150,000 per cubic millimeter). RESULTS: All nine
      patients who had poor responses to intravenous immune globulin also had poor
      responses to splenectomy at one year. Of the 21 patients with good or excellent
      responses to intravenous immune globulin, 19 had good or excellent responses to
      splenectomy. CONCLUSIONS: Patients with idiopathic thrombocytopenic purpura who
      have good or excellent responses to intravenous immune globulin are likely to
      have good or excellent responses to splenectomy, whereas patients who have poor
      responses to intravenous immune globulin are unlikely to have good or excellent
      responses to splenectomy.

PMID- 9154769
TI  - Images in clinical medicine. Perforated duodenal ulcer.

PMID- 9154770
TI  - Use of cardiac procedures and outcomes in elderly patients with myocardial
      infarction in the United States and Canada.
AB  - BACKGROUND: Acute myocardial infarction is a leading cause of morbidity and
      mortality in the United States and Canada. We performed a population-based study
      to compare the use of cardiac procedures and outcomes after acute myocardial
      infarction in elderly patients in the two countries. METHODS: We compared the use
      of invasive cardiac procedures and the mortality rates among 224,258 elderly
      Medicare beneficiaries in the United States and 9444 elderly patients in Ontario,
      Canada, each of whom had a new acute myocardial infarction in 1991. RESULTS: The
      U.S. patients were significantly more likely than the Canadian patients to
      undergo coronary angiography (34.9 percent vs. 6.7 percent, P< 0.001),
      percutaneous transluminal coronary angioplasty (11.7 percent vs. 1.5 percent,
      P<0.001), and coronary-artery bypass surgery (10.6 percent vs. 1.4 percent,
      P<0.001) during the first 30 days after the index infarction. These differences
      in the use of cardiac procedures narrowed but persisted through 180 days of
      follow-up. The 30-day mortality rates were slightly but significantly lower for
      the U.S. patients than for the Canadian patients (21.4 percent vs. 22.3 percent,
      P=0.03). However, the one-year mortality rates were virtually identical (34.3
      percent in the United States vs. 34.4 percent in Ontario, P= 0.94). CONCLUSIONS:
      Short-term mortality after an acute myocardial infarction was slightly lower in
      the United States than in Ontario, but these differences did not persist through
      one year of follow-up. The strikingly higher rates of use of cardiac procedures
      in the United States, as compared with Canada, do not appear to result in better
      long-term survival rates for elderly U.S. patients with acute myocardial
      infarction.

PMID- 9154771
TI  - Management of anticoagulation before and after elective surgery.

PMID- 9154772
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 16-1997. A 42-year-old woman with a pulmonic-valve mass.

PMID- 9154773
TI  - Cardiac pacemakers and cellular telephones.

PMID- 9154774
TI  - Serum mullerian inhibiting substance assay--a new diagnostic test for disorders
      of gonadal development.

PMID- 9154775
TI  - Cardiac procedures, outcomes, and accountability.

PMID- 9154776
TI  - Air embolism during gynecologic endoscopic surgery.

PMID- 9154777
TI  - The outcome of in vitro fertilization and embryo transfer therapy in women with
      endometriosis failing to conceive after laparoscopic conservative surgery.
AB  - STUDY OBJECTIVE: To compare the outcome of in vitro fertilization and embryo
      transfer (IVF-ET) after laparoscopic surgery in women with endometriosis with
      that of patients with tubal factor infertility. DESIGN: Retrospective survey of
      hospital and office charts using a computerized worksheet. SETTING: Lin-Kou
      medical center of Chang Gung Memorial Hospital. PATIENTS: Sixty-seven women with
      minimal to mild or moderate to severe endometriosis. Women with tubal factor
      infertility without other associated disorders (60 cycles) made up the control
      group. INTERVENTIONS: Seventy-five consecutive cycles of IVF-ET were performed in
      these patients who failed to conceive after laparoscopic conservative surgery.
      MEASUREMENTS AND MAIN RESULTS: The concentration of serum estradiol on the day of
      human chorionic gonadotropin (hCG) injection, the day of hCG injection, clinical
      pregnancy rates per transfer, number of follicles larger than 14 mm, number of
      embryos transferred, and implantation rate were not significantly different
      between women with endometriosis and those with tubal factor infertility. The
      number of oocytes retrieved and number fertilized were decreased, and the basal
      level of follicle-stimulating hormone on cycle day 3 was higher in women with
      both degrees of endometriosis. Women in both endometriosis groups received more
      follicle-stimulating hormone and human menopausal gonadotropin than those with
      tubal factor infertility. CONCLUSIONS: The outcome of IVF-ET in patients with
      endometriosis after laparoscopic surgery did not differ from that in the group
      with tubal factor infertility, but the former required more ampules of
      gonadotropin to achieve the same response. The advantages of laparoscopic surgery
      in women with endometriosis should be probably correlated with success of IVF-ET.

PMID- 9154778
TI  - Resumption of menstruation after amenorrhea in women treated by endometrial
      ablation and myometrial resection.
AB  - STUDY OBJECTIVE: To evaluate the prevalence of resumption of menstruation after
      an interval of amenorrhea in women treated by endometrial ablation and myometrial
      resection. DESIGN: Retrospective analysis. SETTING: Tertiary care university
      affiliated teaching hospital. PATIENTS: One hundred fifty-seven consecutive
      patients treated for menorrhagia refractory to medical therapy. INTERVENTIONS:
      Loop resection or rollerball ablation of the endometrium. MEASUREMENTS AND MAIN
      RESULTS: At 6 to 12 months postoperatively, 50. 6% of patients were amenorrheic
      and 35.1% had hypomenorrhea. Over follow-up of 13 to 30 months, 45.1% of women
      became amenorheic and 40.5% had satisfactory hypomenorrhea. Resumption of
      menstruation after any interval of amenorrhea occurred in 27.2% of amenorheic
      patients. We observed an increasing trend to resumption of menstruation after
      rollerball ablation (29.4%) compared with loop resection (26.7%) and after
      preoperative endometrial suppression with buserelin (37.5%) and leuprolide
      (27.1%) compared with danazol (12.5%) and goserelin (10.5%). Resumption of
      menstruation occurred in 44.4% of women who did not have preoperative endometrial
      suppression. CONCLUSIONS: Our results suggest that resumption of menstruation
      does occur after a variable interval of amenorrhea following endometrial ablation
      and myometrial resection. It could potentially be used as a marker of failure of
      endometrial destruction.

PMID- 9154779
TI  - Reproductive performance of women with uterine anomalies after abdominal or
      hysteroscopic metroplasty or no surgical treatment.
AB  - STUDY OBJECTIVE: To evaluate reproductive performance in women with a confirmed
      uterine anomaly treated by abdominal or hysteroscopic metroplasty, or by no
      surgical procedure. DESIGN: Retrospective study. SETTING: A university hospital.
      PATIENTS: Four hundred four women with uterine anomaly, of whom 247 had complete
      or partial septate uterus or partial bicornuate uterus. INTERVENTIONS:
      Hysteroscopic metroplasty was performed in 32 patients with septate or subseptate
      uterus. Twenty women underwent abdominal metroplasty (Jones or Tompkins
      procedure) and 140 had no operative treatment. MEASUREMENTS AND MAIN RESULTS:
      Fetal survival improved from 13% to 91% after hysteroscopic metroplasty and from
      3% to 86% after the abdominal procedure. A living child was born in 67% of 264
      pregnancies in 116 women with septate uterus with no surgical treatment. When 19
      patients with hysteroscopic metroplasty were matched by age, gravidity, and type
      of uterine anomaly with 19 women not subjected to metroplasty, the rates were 86%
      and 68%, respectively (p = 0.089). CONCLUSIONS: Hysteroscopic metroplasty has
      replaced abdominal metroplasty in the treatment of septate uterus. It improves
      the fetal survival rate in women with repeated miscarriage. It does not enhance
      pregnancy rates in infertile women with septate uterus, but as a minimally
      invasive uterine repair, it may be carried out before assisted reproduction.
      Pregnancy in the septate uterus can also progress without any surgical treatment.
      Metroplasty seems to prevent breech delivery and to decrease the cesarean section
      rate, which are potential benefits.

PMID- 9154780
TI  - Laser laparoscopic surgery in the treatment of ovarian endometriomas.
AB  - STUDY OBJECTIVE: To assess the efficacy of laser laparoscopic photocoagulation of
      endometriomas (2-18 cm) in patients with pain, infertility, or a combination of
      the two. DESIGN: Retrospective review of all patients with endometriomas from
      June 1, 1983, to December 31, 1993. SETTING: Department of gynecology and
      obstetrics at a district general hospital and national training center in minimal
      access surgery. PATIENTS: One hundred sixty-five women with large endometriomas
      present at the time of laser laparoscopy. INTERVENTIONS: Carbon dioxide laser or
      potassium-titanyl-phosphate laser laparoscopic surgery. MEASUREMENTS AND MAIN
      RESULTS: Ninety (74%) of 122 patients reported improvement or resolution of pain;
      and 30 of 66 achieved a pregnancy, for a cumulative conception rate of 45%.
      CONCLUSION: Laser laparoscopy is a practical, safe, and effective technique for
      the management of large ovarian endometriomas.

PMID- 9154781
TI  - Endometrial resection and late reoperation in the treatment of menorrhagia.
AB  - STUDY OBJECTIVE: To evaluate the effectiveness of transcervical resection of the
      endometrium and indications for late reoperation. DESIGN: Retrospective study.
      SETTING: Central hospital in northern Norway. PATIENTS: Two hundred fifty women
      (age 30-59 yrs) with dysfunctional bleeding. INTERVENTIONS: Hysteroscopic
      transcervical resection of the endometrium. MEASUREMENTS AND MAIN RESULTS:
      Success as measured by patient satisfaction at 3-month follow-up was 97% and at 4
      to 48 months was 91.6%. Mean observation time was 24 months. Twenty-one women
      required further surgery. Repeat resection was performed in eight women (3.2%),
      of whom 95% were satisfied. Thirteen women (5.2%) had a hysterectomy. Late
      reoperation was performed in 7 patients (2.8%) due to recurrent unacceptable
      vaginal bleeding and in 14 (5.6%) due to late onset of pain. CONCLUSION: After
      endometrial resection, a definite subgroup (8.4%) of women developed late onset
      of pain or bleeding requiring reoperation.

PMID- 9154782
TI  - Transvaginal sonographic and hysteroscopic findings in postmenopausal women
      receiving tamoxifen.
AB  - STUDY OBJECTIVE: To evaluate the effect of tamoxifen on the endometrium. DESIGN:
      Prospective study. SETTING: Department of Obstetrics and Gynecology of the
      University of Rome. PATIENTS: One hundred one postmenopausal women with breast
      cancer receiving tamoxifen 20 to 30 mg/day for at least 1 year; of these 78 were
      asymptomatic and 23 had vaginal bleeding. INTERVENTIONS: All patients underwent
      transvaginal color Doppler sonography. Those with endometrial thickness greater
      than 5 mm were advised to undergo hysteroscopy and if necessary endometrial
      biopsy. For women with endometrial thickness less than 5 mm, hysteroscopy was
      recommended only if irregular endometrial echotexture was observed. MEASUREMENTS
      AND MAIN RESULTS: Eleven (14%) asymptomatic patients and 1 (4.3%) with vaginal
      bleeding had endometrial thickness less than 5 mm (p = 0.4, NS). Women with
      vaginal bleeding had a significantly thicker endometrium than asymptomatic
      patients (15.8 +/- 7.5 vs 11.1 +/- 5.7 mm, p = 0.003). In the asymptomatic group
      31 polyps, 15 atrophic endometria, and 6 hyperplasias were observed. Two
      endometrial cancers, 13 polyps, and 3 hyperplasias were detected in patients with
      vaginal bleeding. Hysteroscopy did not always allow endometrial biopsy, even in
      the presence of increased endometrial thickness with or without irregular
      surface. No statistical differences were found for mean pulsatility and
      resistance indexes of uterine and endometrial arteries between symptomatic and
      asymptomatic women, but these indexes were significantly lower compared with
      normal postmenopausal values. CONCLUSION: Women receiving tamoxifen, especially
      those who are asymptomatic, should be closely monitored by transvaginal
      sonography and hysteroscopy to detect endometrial pathologies.

PMID- 9154783
TI  - Long-term results of laparoscopic Burch urethropexy.
AB  - STUDY OBJECTIVE: To evaluate the long-term efficacy of laparoscopic Burch
      urethropexy. DESIGN: Pilot study. SETTING: Private practice. PATIENTS: Thirty
      five consecutive women (average age 45.5 yrs, average parity 2.3, average weight
      67.7 kg) treated for genuine stress incontinence between May 1992 and July 1994.
      INTERVENTIONS: Urethropexy was performed with curved needle suturing in 7 women,
      straight needle suturing in 5, and Stamey needle suturing in 23. Twenty-five
      (71.4%) patients had concomitant pelvic surgery. MEASUREMENTS AND MAIN RESULTS:
      Wilcoxon two-sample, chi2, and Fisher's exact tests were performed to determine
      which variables were significantly associated with surgical success. Average
      operating time was 190 minutes, hospitalization 24 hours, and catheterization 5
      days. The cure rate of stress incontinence was 89% 3 months and 86% 1 year after
      surgery. At average follow-up of 34 months, only 68.6% of patients reported
      complete or almost complete cure, 11.4% were improved, and 20% were complete
      failures. The only operative variable approaching statistical significance for
      predicting surgical success was type of suture needle (p = 0.07), with the Stamey
      needle group having the highest cure rate. Women who were cured or almost cured
      had a significantly shorter follow-up than those who were improved or failures (p
      = 0.001). CONCLUSION: The success rate of laparoscopic Burch urethropexy compares
      with that of open Burch procedure at 1 year, but drops considerably thereafter.

PMID- 9154784
TI  - Skin closure at laparoscopy.
AB  - STUDY OBJECTIVE: To discern the best method of wound closure after laparoscopy
      based on patient acceptability of pain, complications, and cosmetic result.
      DESIGN: Randomized, prospective study. SETTING: A university-affiliated hospital.
      PATIENTS: Fifty-four women. Interventions. The women received interrupted 3-0
      nylon sutures, subcuticular 3-0 polyglactin 910 sutures, or adhesive strips for
      skin closure. At the umbilical port site the rectus sheath was closed with a
      single 0 polyglactin suture and then one of the three materials for skin closure.
      The lateral ports were closed with a combination of these materials, allowing
      each patient to act as her own control. MEASUREMENTS AND MAIN RESULTS: Pain was
      significantly less in wounds closed by subcuticular technique than in those
      closed by either transcutaneous suture or adhesive strips. This was seen for the
      5-mm, 10-mm, and umbilical port sites. There was no statistically significant
      difference in the rate of reported complications or patient satisfaction between
      subcuticular and transcutaneous wound sites. CONCLUSION: We believe these results
      support subcuticular methods of wound closure after laparoscopic procedures.

PMID- 9154785
TI  - Anterior abdominal wall adhesions after laparotomy or laparoscopy.
AB  - STUDY OBJECTIVE: To determine the frequency of postoperative adhesions to the
      anterior abdominal wall peritoneum that could affect safe placement of the
      initial laparoscopic umbilical cannula at subsequent procedures. DESIGN:
      Prospective cohort study. SETTING: Reproductive endocrinology and infertility
      service of a tertiary care referral hospital. PATIENTS: Two hundred fifteen
      women, 124 with prior abdominal surgery and 91 with no prior surgery.
      INTERVENTIONS: Surgical histories were reviewed, abdominal skin scars noted, and
      extent of anterior abdominal wall adhesions prospectively recorded. Statistical
      analysis was performed with the chi2 test. MEASUREMENTS AND MAIN RESULTS: No
      anterior abdominal wall adhesions were present in 91 patients with no previous
      surgery or 45 patients with previous laparoscopy (12 had more than 1 laparoscopy;
      p <0.001 vs laparotomy). Seventeen (59%) of 29 patients with a midline vertical
      incision had anterior wall adhesions (p <0.05 vs suprapubic transverse incision).
      Eleven (28%) of 39 with a suprapubic transverse incision had anterior wall
      adhesions (p <0.001 vs no surgery or laparoscopy). Ninety-six percent of
      adhesions involved omentum and 29% included bowel. CONCLUSION: Prior laparotomy,
      whether through a midline vertical or suprapubic transverse incision,
      significantly increased the frequency of anterior abdominal wall adhesions, and
      these adhesions may complicate the placement of the laparoscopic cannula through
      the umbilicus.

PMID- 9154786
TI  - Monitoring fluid absorption using 1% ethanol-tagged glycine during operative
      hysteroscopy.
AB  - STUDY OBJECTIVE: To assess the value of expired breath ethanol as a marker of
      irrigating fluid absorption during hysteroscopic surgery using 1% ethanol-tagged
      1.5% glycine. DESIGN: Prospective analysis. SETTING: Endoscopy training center of
      a university hospital. PATIENTS: Forty-eight women undergoing major hysteroscopic
      surgery for menorrhagia (40 transcervical endometrial resections, 8 rollerball
      endometrial ablations). INTERVENTIONS: Expired breath ethanol and venous blood
      samples were taken before and at 10-minute intervals during surgery. Volumetric
      absorption of irrigating fluid was checked at the same time. MEASUREMENTS AND
      MAIN RESULTS: Expired breath ethanol concentration, serum ethanol, several
      biochemical variables, and volume of absorbed irrigating fluid (direct and
      indirect) were measured. There was a linear positive correlation (r = 0.86, p
      <0.001) between direct vascular absorption of the irrigating fluid and expired
      breath ethanol concentration. Prediction can be given with 95% confidence that if
      the alcolmeter reading is below 0.45%, the volume of irrigating fluid absorbed is
      below 2000 ml. No significant correlation was seen between expired breath ethanol
      and indirect fluid absorption. CONCLUSIONS: As it is not possible to distinguish
      direct and indirect fluid absorption during hysteroscopic surgery, measuring
      expired breath ethanol is insufficient to assess overall fluid balance, and
      continuous volumetric assessment is still required.

PMID- 9154787
TI  - Operative laparoscopy for management of ectopic pregnancy in patients with
      hypovolemic shock.
AB  - STUDY OBJECTIVE: To determine the safety of operative laparoscopy in the
      management of ectopic pregnancy in women with hypovolemic shock. DESIGN:
      Retrospective chart review. SETTING: University-affiliated hospital. PATIENTS:
      Two hundred eleven women with tubal pregnancy, of whom 33 were suffering from
      hypovolemic shock, based on a combination of signs and symptoms including
      hypotension, tachycardia, anxiety, thirst, tachypnea, and slow capillary refill.
      INTERVENTION: Laparoscopic surgery. MEASUREMENTS AND MAIN RESULTS: Mean +/- SEM
      intraabdominal blood loss was significantly (p <0.01) higher in women with
      hypovolemic shock, 1369 +/- 149 versus 114 +/- 14 ml. Blood transfusions were
      given to 88% and 0.5%, respectively (p <0. 01). Laparoscopic salpingectomy was
      performed in all hemodynamically compromised women compared with 87% of stable
      women. Conversion to laparotomy was required in three patients in the hypovolemic
      shock group and five in the stable group. All patients had an uncomplicated
      postoperative course and made a full recovery. CONCLUSION: The availability of
      optimal anesthesia and advanced cardiovascular monitoring, and the ability to
      convert rapidly to laparotomy if required, allow safe performance of operative
      laparoscopic surgery in most women in hypovolemic shock. In fact, the superior
      exposure of laparoscopy, providing rapid diagnosis and control of the source of
      bleeding, makes it a highly suitable approach.

PMID- 9154788
TI  - Endometrial ablation and hysteroscopic myomectomy by electrosurgical
      vaporization.
AB  - Electrosurgical vaporization, first performed by urologists in prostate surgery,
      is useful during operative hysteroscopy for endometrial ablation and myomectomy.
      From June 1995 through May 1996, 9 surgeons performed 44 endometrial ablations
      and hysteroscopic myomectomies using the vaporization electrode. Our experience
      with this technique thus far has been very favorable. The procedure is less
      expensive than laser ablation and is easier to teach than wire loop resection. It
      is also less tedious than wire loop resection since myoma chips that often
      obstruct the operator's view are eliminated. Long-term efficacy of this technique
      remains to be proved.

PMID- 9154789
TI  - Hysteroscopic fluid management.
AB  - Many of the technical difficulties and hazards associated with operative
      hysteroscopy revolve around management of the liquid distending medium. For the
      nurse, this involves vigilance in determining when the reservoir bag needs to be
      changed and when the return canister is full, and the task of calculating inflow
      outflow deficits. The last is made more difficult by the fact that 3-L bags of
      dilute sorbitol or glycine most often used in hysteroscopy are not filled
      precisely, and readings of residual reservoir volume and canister levels are
      often made in darkened operating rooms. For the surgeon, the first issue is to
      achieve satisfactory intrauterine visualization that relates to the pressure and
      the flow of medium. Both surgeon and patient are understandably concerned about
      problems of excessive absorption of water from the electrolyte-free medium
      causing potentially life-threatening hyponatremia and hypervolemia. A system to
      manage hysteroscopic fluid was developed that addresses these concerns.

PMID- 9154792
TI  - Injuries to major blood vessels during endoscopy.
AB  - Major blood vessel injury is a true emergency during endoscopic procedures. Too
      often, fear of litigation quashes the opportunity to assess the cause and learn
      from the experience of others. Frequently, only through a medicolegal review can
      such events be evaluated. A review of 47 such cases highlighted several key
      lessons. Proper technique for inserting the Veress needle, laparoscopic cannula,
      and open cannulas can prevent most accidents. If standard precautions during
      insertion are breached, safety shields on disposable cannula sleeves may not
      prevent or reduce the risk of major vessel injury. Distorted anatomy or steep
      Trendelenburg position may increase the risk. Retroperitoneal hematomas require
      exploratory laparotomy for proper assessment. Dissections around the great
      vessels of the pelvis require the same methods and precautions during laparoscopy
      as during laparotomy.

PMID- 9154790
TI  - Laparoscopic rectocele repair using polyglactin mesh.
AB  - We assessed the efficacy of laparoscopic treatment of rectocele defect using a
      polyglactin mesh graft. From May 1, 1995, through September 30, 1995, we
      prospectively evaluated 20 women (age 38-74 yrs) undergoing pelvic floor
      reconstruction for symptomatic pelvic floor prolapse, with or without
      hysterectomy. Morbidity of the procedure was extremely low compared with standard
      transvaginal and transrectal approaches. Patients were followed at 3-month
      intervals for 1 year. Sixteen had resolution of symptoms. Laparoscopic
      application of polyglactin mesh for the repair of the rectocele defect is a
      viable option, although long-term follow-up is necessary.

PMID- 9154791
TI  - Development and use of a bipolar resectoscope in endometrial electrosurgery.
AB  - We conducted a prospective, blinded study to compare the tissue response and
      mechanical properties of a bipolar resectoscope with standard monopolar cutting
      and coagulation instruments. At the animal care facility of Tufts Medical School
      (Medford, MA), four surgeons blinded to instrumentation and distention media cut
      segments out of a rabbit uterine horn and desiccated the abdominal wall using
      either the bipolar device in 0.9% saline or the monopolar system in 1.5% glycine.
      Both systems used a Force 2 Valleylab radiofrequency generator at identical power
      settings. Cut and desiccated sections were fixed and stained with hematoxylin and
      eosin as well as Masson's trichrome to evaluate thermal damage. The pathologist
      was blinded to the system used to make the cut or desiccation. Both systems cut
      and coagulated tissue with similar properties. Most surgeons noted a longer delay
      from radiofrequency activation to actual cutting with the bipolar system. The
      depth of thermal damage when cutting or desiccating tissue was similar for the
      two systems. This disposable, inexpensive device allows for standard
      resectoscopic hardware to be transformed into a bipolar device. All current
      techniques of intrauterine cutting and coagulation may soon be performed in the
      presence of physiologic uterine distention media. Human clinical data remain to
      be gathered.

PMID- 9154793
TI  - Venous air embolism during operative hysteroscopy.
AB  - The world literature, including hospital and medicolegal case records, was
      reviewed to collate cases of venous air embolism resulting from the increasing
      number of operative hysteroscopies being performed. Seven women undergoing
      operative hysteroscopy for five different indications had clear-cut evidence of
      venous air embolism early in the course of the procedure. Five of these patients
      died. This complication is rare but devastating, resulting from traumatic opening
      into large uterine sinuses, especially with the patient in the Trendelenburg
      position, when the heart is below the level of the uterus. Several steps can be
      taken to try to prevent this problem.

PMID- 9154794
TI  - Data structuring.

PMID- 9154795
TI  - Accurate positioning of RNA polymerase II on a natural TATA-less promoter is
      independent of TATA-binding-protein-associated factors and initiator-binding
      proteins.
AB  - Two promoter elements, the TATA element and initiator (Inr), are capable of
      directing specific transcription initiation of protein-encoding genes by RNA
      polymerase II (RNAPII). Although binding to the TATA element by the TATA-binding
      protein (TBP) has been shown to be the initial recognition step in transcription
      complex formation in vitro, the mechanism through which the basal machinery
      assembles into a functional complex on TATA-less promoters is controversial.
      Evidence supporting numerous models of Inr-mediated transcription complex
      formation exists, including the nucleation of a complex by Inr-binding proteins,
      a component of the TFIID complex, or a specific upstream activator common to many
      TATA-less promoters, Sp1. Using various techniques, we have undertaken a
      systematic analysis of the natural TATA-less human DNA polymerase beta (beta-pol)
      gene promoter. Although the beta-pol promoter contains upstream Sp1 elements and
      a functional Inr that binds YY1, neither of these factors is essential for Inr
      mediated transcription complex formation. A complex containing TBP, TFIIB, TFIIF,
      and RNAPII (DBPolF complex) is capable of forming on the promoter in an Inr
      dependent manner. A single point mutation within the Inr that affects DBPolF
      complex formation diminishes beta-pol transcriptional activity.

PMID- 9154796
TI  - Exon skipping and circular RNA formation in transcripts of the human cytochrome P
      450 2C18 gene in epidermis and of the rat androgen binding protein gene in
      testis.
AB  - The cytochrome P-450 2C18 gene was found by reverse transcription-PCR to
      represent the most abundantly expressed gene of the P-450 2C subfamily in human
      epidermis. However, in addition to the canonical mRNA of nine exons, transcripts
      that have skipped exon 4 or 5, exons 4, 5, and 6, or exons 4, 5, 6, and 7 were
      also identified in this tissue. Remarkably, circular RNA transcripts synthesized
      by the joining of the donor and acceptor splice sites of the same exon were
      detected in human epidermis for exons 4 and 5. Moreover, molecules composed of
      exons 4, 5, and 6 with the donor splice site of exon 6 joined to the acceptor
      splice site of exon 4 or composed of exons 4, 5, 6, and 7 with the donor splice
      site of exon 7 joined to the acceptor splice site of exon 4 were also found to be
      present in this tissue. In rat testis, a similar analysis allowed the detection
      of a circular RNA molecule composed of exons 6 and 7 of the androgen binding
      protein (ABP) gene, with the donor splice site of exon 7 joined to the acceptor
      splice site of exon 6, and of an ABP mRNA which had skipped exons 6 and 7. These
      results apparently substantiate the hypothesis that alternative pre-mRNA splicing
      has the potential to generate not only mRNAs that lack one or more exons but also
      circular RNA molecules that are composed of the exons that are skipped. However,
      additional 2C18 circular species containing various combinations of exons were
      also detected in human epidermis, and an exon 6-skipped ABP mRNA molecule was
      identified in rat testis. This observation is interpreted as indicative that at
      low frequency, numerous circular RNA formation and exon skipping events may
      occur, allowing the joining of a variety of different combinations of exons.
      Moreover, the relative stability of these molecules is apparently the key factor
      that determines the relative ease of their detection.

PMID- 9154797
TI  - The STK2 gene, which encodes a putative Ser/Thr protein kinase, is required for
      high-affinity spermidine transport in Saccharomyces cerevisiae.
AB  - Eukaryotic polyamine transport systems have not yet been characterized at the
      molecular level. We have used transposon mutagenesis to identify genes
      controlling polyamine transport in Saccharomyces cerevisiae. A haploid yeast
      strain was transformed with a genomic minitransposon- and lacZ-tagged library,
      and positive clones were selected for growth resistance to methylglyoxal
      bis(guanylhydrazone) (MGBG), a toxic polyamine analog. A 747-bp DNA fragment
      adjacent to the lacZ fusion gene rescued from one MGBG-resistant clone mapped to
      chromosome X within the coding region of a putative Ser/Thr protein kinase gene
      of previously unknown function (YJR059w, or STK2). A 304-amino-acid stretch
      comprising 11 of the 12 catalytic subdomains of Stk2p is approximately 83%
      homologous to the putative Pot1p/Kkt8p (Stk1p) protein kinase, a recently
      described activator of low-affinity spermine uptake in yeast. Saturable
      spermidine transport in stk2::lacZ mutants had an approximately fivefold-lower
      affinity and twofold-lower Vmax than in the parental strain. Transformation of
      stk2::lacZ cells with the STK2 gene cloned into a single-copy expression vector
      restored spermidine transport to wild-type levels. Single mutants lacking the
      catalytic kinase subdomains of STK1 exhibited normal parameters for the initial
      rate of spermidine transport but showed a time-dependent decrease in total
      polyamine accumulation and a low-level resistance to toxic polyamine analogs.
      Spermidine transport was repressed by prior incubation with exogenous spermidine.
      Exogenous polyamine deprivation also derepressed residual spermidine transport in
      stk2::lacZ mutants, but simultaneous disruption of STK1 and STK2 virtually
      abolished high-affinity spermidine transport under both repressed and derepressed
      conditions. On the other hand, putrescine uptake was also deficient in stk2::lacZ
      mutants but was not repressed by exogenous spermidine. Interestingly, stk2::lacZ
      mutants showed increased growth resistance to Li+ and Na+, suggesting a
      regulatory relationship between polyamine and monovalent inorganic cation
      transport. These results indicate that the putative STK2 Ser/Thr kinase gene is
      an essential determinant of high-affinity polyamine transport in yeast whereas
      its close homolog STK1 mostly affects a lower-affinity, low-capacity polyamine
      transport activity.

PMID- 9154798
TI  - T cells deficient in inositol 1,4,5-trisphosphate receptor are resistant to
      apoptosis.
AB  - The type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) calcium release channel
      is present on the endoplasmic reticulum of most cell types. T lymphocytes which
      have been made deficient in IP3R1 lack detectable IP3-induced intracellular
      calcium release and exhibit defective signaling via the T-cell receptor (TCR) (T.
      Jayaraman, E. Ondriasova, K. Ondrias, D. Harnick, and A. R. Marks, Proc. Natl.
      Acad. Sci. USA 92:6007-6011, 1995). We now show that IP3R1-deficient T cells are
      resistant to apoptosis induced by dexamethasone, TCR stimulation, ionizing
      radiation, and Fas. Resistance to TCR-mediated apoptosis in IP3R1-deficient cells
      is reversed by pharmacologically raising cytoplasmic calcium levels. TCR-mediated
      apoptosis can be induced in calcium-free media, indicating that extracellular
      calcium influx is not required. These findings suggest that intracellular calcium
      release via the IP3R1 is a critical mediator of apoptosis.

PMID- 9154800
TI  - The signal response of IkappaB alpha is regulated by transferable N- and C
      terminal domains.
AB  - IkappaB alpha retains the transcription factor NF-kappaB in the cytoplasm, thus
      inhibiting its function. Various stimuli inactivate IkappaB alpha by triggering
      phosphorylation of the N-terminal residues Ser32 and Ser36. Phosphorylation of
      both serines is demonstrated directly by phosphopeptide mapping utilizing calpain
      protease, which cuts approximately 60 residues from the N terminus, and by
      analysis of mutants lacking one or both serine residues. Phosphorylation is
      followed by rapid proteolysis, and the liberated NF-kappaB translocates to the
      nucleus, where it activates transcription of its target genes. Transfer of the N
      terminal domain of IkappaB alpha to the ankyrin domain of the related oncoprotein
      Bcl-3 or to the unrelated protein glutathione S-transferase confers signal
      induced phosphorylation on the resulting chimeric proteins. If the C-terminal
      domain of IkappaB alpha is transferred as well, the resulting chimeras exhibit
      both signal-induced phosphorylation and rapid proteolysis. Thus, the signal
      response of IkappaB alpha is controlled by transferable N-terminal and C-terminal
      domains.

PMID- 9154799
TI  - Distinct retinoid X receptor-retinoic acid receptor heterodimers are
      differentially involved in the control of expression of retinoid target genes in
      F9 embryonal carcinoma cells.
AB  - The F9 murine embryonal carcinoma cell line represents a well-established system
      for the study of retinoid signaling in vivo. We have investigated the functional
      specificity of different retinoid X receptor (RXR)-retinoic acid (RA) receptor
      (RAR) isotype pairs for the control of expression of endogenous RA-responsive
      genes, by using wild-type (WT), RXR alpha(-/-), RAR alpha(-/-), RAR gamma(-/-),
      RXR alpha(-/-)-RAR alpha(-/-), and RXR alpha(-/-)-RAR gamma(-/-) F9 cells, as
      well as panRXR and RAR isotype (alpha, beta, and gamma)-selective retinoids. We
      show that in these cells the control of expression of different sets of RA
      responsive genes is preferentially mediated by distinct RXR-RAR isotype
      combinations. Our data support the conclusion that RXR-RAR heterodimers are the
      functional units transducing the retinoid signal and indicate in addition that
      these heterodimers exert both specific and redundant functions on the expression
      of particular sets of RA-responsive genes. We also show that the presence of a
      given receptor isotype can hinder the activity of another isotype and therefore
      that functional redundancy between retinoid receptor isotypes can be
      artifactually generated by gene knockouts.

PMID- 9154801
TI  - Human La protein: a stabilizer of histone mRNA.
AB  - Histone mRNA is destabilized at the end of S phase and in cell-free mRNA decay
      reaction mixtures supplemented with histone proteins, indicating that histones
      might autoregulate the histone mRNA half-life. Histone mRNA destabilization in
      vitro requires three components: polysomes, histones, and postpolysomal
      supernatant (S130). Polysomes are the source of the mRNA and mRNA-degrading
      enzymes. To investigate the role of the S130 in autoregulation, crude S130 was
      fractionated by histone-agarose affinity chromatography. Two separate activities
      affecting the histone mRNA half-life were detected. The histone-agarose-bound
      fraction contained a histone mRNA destabilizer that was activated by histone
      proteins; the unbound fraction contained a histone mRNA stabilizer. Further
      chromatographic fractionation of unbound material revealed only a single protein
      stabilizer, which was purified to homogeneity, partially sequenced, and found to
      be La, a well-characterized RNA-binding protein. When purified La was added to
      reaction mixtures containing polysomes, a histone mRNA decay intermediate was
      stabilized. This intermediate corresponded to histone mRNA lacking 12 nucleotides
      from its 3' end and containing an intact coding region. Anti-La antibody blocked
      the stabilization effect. La had little or no effect on several other cell cycle
      regulated mRNAs. We suggest that La prolongs the histone mRNA half-life during S
      phase and thereby increases histone protein production.

PMID- 9154803
TI  - Interaction of activated Ras with Raf-1 alone may be sufficient for
      transformation of rat2 cells.
AB  - v-H-ras effector mutants have been assessed for transforming activity and for the
      ability of the encoded proteins to interact with Raf-1-, B-Raf-, byr2-, ralGDS-,
      and CDC25-encoded proteins in the yeast two-hybrid system. Transformation was
      assessed in rat2 cells as well as in a mutant cell line, rv68BUR, that affords a
      more sensitive transformation assay. Selected mutant Ras proteins were also
      examined for their ability to interact with an amino-terminal fragment of Raf-1
      in vitro. Finally, possible cooperation between different v-H-ras effector
      mutants and between effector mutants and overexpressed Raf-1 was assessed. Ras
      transforming activity was shown to correlate best with the ability of the encoded
      protein to interact with Raf-1. No evidence for cooperation between v-H-ras
      effector mutants was found. Signaling through the Raf1-MEK-mitogen-activated
      protein kinase cascade may be the only effector pathway contributing to RAS
      transformation in these cells.

PMID- 9154802
TI  - Reconstitution of a MEC1-independent checkpoint in yeast by expression of a novel
      human fork head cDNA.
AB  - A novel human cDNA, CHES1 (checkpoint suppressor 1), has been isolated by
      suppression of the mec1-1 checkpoint mutation in Saccharomyces cerevisiae. CHES1
      suppresses a number of DNA damage-activated checkpoint mutations in S.
      cerevisiae, including mec1, rad9, rad24, dun1, and rad53. CHES1 suppression of
      sensitivity to DNA damage is specific for checkpoint-defective strains, in
      contrast to DNA repair-defective strains. Presence of CHES1 but not a control
      vector resulted in G2 delay after UV irradiation in checkpoint-defective strains,
      with kinetics, nuclear morphology, and cycloheximide resistance similar to those
      of a wild-type strain. CHES1 can also suppress the lethality, UV sensitivity, and
      G2 checkpoint defect of a mec1 null mutation. In contrast to this activity, CHES1
      had no measurable effect on the replication checkpoint as assayed by hydroxyurea
      sensitivity of a mec1 strain. Sequence analysis demonstrates that CHES1 is a
      novel member of the fork head/Winged Helix family of transcription factors.
      Suppression of the checkpoint-defective phenotype requires a 200-amino-acid
      domain in the carboxy terminus of the protein which is distinct from the DNA
      binding site. Analysis of CHES1 activity is most consistent with activation of an
      alternative MEC1-independent checkpoint pathway in budding yeast.

PMID- 9154804
TI  - Regulation of K3 keratin gene transcription by Sp1 and AP-2 in differentiating
      rabbit corneal epithelial cells.
AB  - Rabbit corneal epithelial cells cultured in the presence of 3T3 feeder cells
      undergo biochemical differentiation, as evidenced by their initial expression of
      K5 and K14 keratins characteristic of basal keratinocytes, followed by the
      subsequent expression of K3 and K12 keratin markers of corneal epithelial
      differentiation. Previous data established that mutations of an Sp1 site in a DNA
      element, E, that contains overlapping Sp1 and AP-2 motifs reduce K3 gene promoter
      activity by 70% in transfection assays. We show here that Sp1 activates while AP
      2 represses the K3 promoter. Although undifferentiated corneal epithelial basal
      cells express equal amounts of Sp1 and AP-2 DNA-binding activities, the
      differentiated cells down-regulate their Sp1 activity slightly but their AP-2
      activity drastically, thus resulting in a six- to sevenfold increase in the
      Sp1/AP-2 ratio. This change coincides with the activation and suppression of the
      differentiation-related K3 gene and the basal cell-related K14 keratin gene,
      respectively. In addition, we show that polyamines, which are present in a high
      concentration in proliferating basal keratinocytes, can inhibit the binding of
      Sp1 to its cognate binding motif but not that of AP-2. These results suggest that
      the relatively low Sp1/AP-2 ratio as well as the polyamine-mediated inhibition of
      Sp1 binding to the E motif may account, in part, for the suppression of the K3
      gene in corneal epithelial basal cells, while the elevated Sp1/AP-2 ratio may be
      involved in activating the K3 gene in differentiated corneal epithelial cells.
      Coupled with the previous demonstration that AP-2 activates the K14 gene in basal
      cells, the switch of the Sp1/AP-2 ratio during corneal epithelial differentiation
      may play a role in the reciprocal expression of the K3 and K14 genes in the basal
      and suprabasal cell layers.

PMID- 9154805
TI  - Role of the Ada adaptor complex in gene activation by the glucocorticoid
      receptor.
AB  - We have shown that the Ada adaptor complex is important for the gene activation
      capacity of the glucocorticoid receptor in yeast. The recently isolated human
      Ada2 protein also increases the potency of the receptor protein in mammalian
      cells. The Ada pathway is of key significance for the tau1 core transactivation
      domain (tau1c) of the receptor, which requires Ada for activity in vivo and in
      vitro. Ada2 can be precipitated from nuclear extracts by a glutathione S
      transferase-tau1 fusion protein coupled to agarose beads, and a direct
      interaction between Ada2 and tau1c can be shown by using purified proteins. This
      interaction is strongly reduced by a mutation in tau1c that reduces
      transactivation activity. Mutations affecting the Ada complex do not reverse
      transcriptional squelching by the tau1 domain, as they do for the VP16
      transactivation domain, and thus these powerful acidic activators differ in at
      least some important aspects of gene activation. Mutations that reduce the
      activity of the tau1c domain in wild-type yeast strains cause similar reductions
      in ada mutants that contain little or no Ada activity. Thus, gene activation
      mechanisms, in addition to the Ada pathway, are involved in the activity of the
      tau1c domain.

PMID- 9154806
TI  - p53 transactivation and protein accumulation are independently regulated by UV
      light in different phases of the cell cycle.
AB  - DNA damage-induced activation of the p53 tumor suppressor gene is suggested to be
      central in the cellular damage response pathway. In this study, we analyzed the
      responses of p53 to UVC radiation in synchronized mouse fibroblasts in terms of
      p53 accumulation, transcriptional activation, and sequence-specific DNA-binding
      activity. UVC was found to induce accumulation of p53 cell cycle dependently in
      G1/S- and S-phase cells but not in G0 or G1 cells. In contrast, p53
      transcriptional activity and its target genes, p21 and GADD45, were stimulated by
      UVC in G0 and G1 cells in the absence of detectable p53 protein. The accumulation
      of p53 and increased p21 and GADD45 expression were replication dependent in S
      phase cells. Interestingly, sequence-specific p53 DNA-binding activity was
      stimulated also replication independently in S phase, though the effect was not
      conveyed to stimulation of p53 target genes, suggesting that additional events
      are required for p53-stimulated gene expression. The results show that opposed to
      the cell cycle dependence of p53 accumulation, the UVC-mediated transactivation
      by p53 is independent of the cell cycle phase and protein stabilization.

PMID- 9154807
TI  - Structure-function analysis of TAF130: identification and characterization of a
      high-affinity TATA-binding protein interaction domain in the N terminus of yeast
      TAF(II)130.
AB  - We report structure-function analyses of TAF130, the single-copy essential yeast
      gene encoding the 130,000-Mr yeast TATA-binding protein (TBP)-associated factor
      TAF(II)130 (yTAF(II)130). A systematic family of TAF130 mutants was generated,
      and these mutant TAF130 alleles were introduced into yeast in both single and
      multiple copies to test for their ability to complement a taf130delta null allele
      and support cell growth. All mutant proteins were stably expressed in vivo. The
      complementation tests indicated that a large portion (amino acids 208 to 303 as
      well as amino acids 367 to 1037) of yTAF(II)130 is required to support cell
      growth. Direct protein blotting and coimmunoprecipitation analyses showed that
      two N-terminal deletions which remove portions of yTAF(II)130 amino acids 2 to
      115 dramatically decrease the ability of these mutant yTAF(II)130 proteins to
      bind TBP. Cells bearing either of these two TAF130 mutant alleles also exhibit a
      slow-growth phenotype. Consistent with these observations, overexpression of TBP
      can correct this growth deficiency as well as increase the amount of TBP
      interacting with yTAF(II)130 in vivo. Our results provide the first combined
      genetic and biochemical evidence that yTAF(II)130 binds to yeast TBP in vivo
      through yTAF(II)130 N-terminal sequences and that this binding is physiologically
      significant. By using fluorescence anisotropy spectroscopic binding measurements,
      the affinity of the interaction of TBP for the N-terminal TBP-binding domain of
      yTAF(II)130 was measured, and the Kd was found to be about 1 nM. Moreover, we
      found that the N-terminal domain of yTAF(II)130 actively dissociated TBP from
      TATA box-containing DNA.

PMID- 9154808
TI  - Isolation of an AP-1 repressor by a novel method for detecting protein-protein
      interactions.
AB  - Transcription factor AP-1 transduces environmental signals to the transcriptional
      machinery. To ensure a quick response yet maintain tight control over AP-1 target
      genes, AP-1 activity is likely to be negatively regulated in nonstimulated cells.
      To identify proteins that interact with the Jun subunits of AP-1 and repress its
      activity, we developed a novel screen for detecting protein-protein interactions
      that is not based on a transcriptional readout. In this system, the mammalian
      guanyl nucleotide exchange factor (GEF) Sos is recruited to the Saccharomyces
      cerevisiae plasma membrane harboring a temperature-sensitive Ras GEF, Cdc25-2,
      allowing growth at the nonpermissive temperature. Using the Sos recruitment
      system, we identified new c-Jun-interacting proteins. One of these, JDP2,
      heterodimerizes with c-Jun in nonstimulated cells and represses AP-1-mediated
      activation.

PMID- 9154809
TI  - A novel mutant allele of Schizosaccharomyces pombe rad26 defective in monitoring
      S-phase progression to prevent premature mitosis.
AB  - A semipermissive growth condition was defined for a Schizosaccharomyces pombe
      strain carrying a thermosensitive allele of DNA polymerase delta (pol delta
      ts03). Under this condition, DNA polymerase delta is semidisabled and causes a
      delay in S-phase progression. Using a genetic strategy, we have isolated a panel
      of mutants that enter premature mitosis when DNA replication is incomplete but
      which are not defective for arrest in G2/M following DNA damage. We characterized
      the aya14 mutant, which enters premature mitosis when S phase is arrested by
      genetic or chemical means. However, this mutant is sensitive to neither UV nor
      gamma irradiation. Two genomic clones, rad26+ and cds1+, were found to suppress
      the hydroxyurea sensitivity of the aya14 mutant. Genetic analysis indicates that
      aya14 is a novel allele of the cell cycle checkpoint gene rad26+, which we have
      named rad26.a14. cds1+ is a suppressor which suppresses the S-phase feedback
      control defect of rad26.a14 when S phase is inhibited by either hydroxyurea or
      cdc22, but it does not suppress the defect when S phase is arrested by a mutant
      DNA polymerase. Analyses of rad26.a14 in a variety of cdc mutant backgrounds
      indicate that strains containing rad26.a14 bypass S-phase arrest but not G1 or
      late S/G2 arrest. A model of how Rad26 monitors S-phase progression to maintain
      the dependency of cell cycle events and coordinates with other rad/hus checkpoint
      gene products in responding to radiation damage is proposed.

PMID- 9154810
TI  - Regulated expression and RNA processing of transcripts from the Srp20 splicing
      factor gene during the cell cycle.
AB  - Eukaryotic splicing factors belonging to the SR family are essential splicing
      factors consisting of an N-terminal RNA-binding region and a C-terminal RS
      domain. They are believed to be involved in alternative splicing of numerous
      transcripts because their expression levels can influence splice site selection.
      We have characterized the structure and transcriptional regulation of the gene
      for the smallest member of the SR family, SRp20 (previously called X16). The
      mouse gene encoding SRp20, termed Srp20, consists of one alternative exon and six
      constitutive exons and was mapped to a 2-centimorgan interval on chromosome 17.
      When cells are transfected with SRp20 genomic DNA, both standard and
      alternatively spliced transcripts and corresponding proteins are produced.
      Interestingly, in starved (G0) cells, the amount of SRp20 mRNA containing the
      alternative exon is large, whereas the amount of the standard SRp20 mRNA without
      the alternative exon is small. When starved cells are stimulated with serum, the
      alternative form is lost and the standard form is induced. These results suggest
      that splicing could be regulated during the cell cycle and that this could be, at
      least in part, due to regulated expression of SR proteins. Consistent with this,
      experiments with synchronized cells showed an induction of SRp20 transcripts in
      late G1 or early S. We have also characterized the promoter of SRp20. It lies
      within a GC-rich CpG island and contains two consensus binding sites for E2F, a
      transcription factor thought to be involved in regulating the cell cycle. These
      motifs may be functional since reporter constructs with the SRp20 promoter can be
      stimulated by cotransfection with E2F expression plasmids.

PMID- 9154811
TI  - Cryptic signals and the fidelity of V(D)J joining.
AB  - V(D)J recombination is responsible for the de novo creation of antigen receptor
      genes in T- and B-cell precursors. To the extent that lymphopoiesis takes place
      throughout an animal's lifetime, recombination errors present an ongoing problem.
      One type of aberrant rearrangement ensues when DNA sequences resembling a V(D)J
      joining signal are targeted by mistake. This study investigates the type of
      sequence likely to be subject to mistargeting, the level of joining-signal
      function associated with these sequences, and the number of such cryptic joining
      signals in the genome.

PMID- 9154812
TI  - Two types of zinc fingers are required for dimerization of the serendipity delta
      transcriptional activator.
AB  - The serendipity (sry) delta zinc finger protein controls bicoid gene expression
      during Drosophila melanogaster oogenesis. In addition, sry delta mutants display
      various zygotic phenotypes, ranging from abnormal embryogenesis to sex-biased
      adult lethality. We report here that sry delta is a sequence-specific
      transcriptional activator. A single sry delta consensus binding site (SDCS), in
      either orientation, is sufficient to promote transcription activation in cell
      culture, and multiple SDCSs mediate a strong synergistic activation, reflecting
      the cooperativity of sry delta binding to DNA. Further, several lines of evidence
      strongly suggest that sry delta binds to DNA as a dimer. While each of three
      point mutations located in the third zinc finger of sry delta drastically reduces
      its DNA binding affinity, a fourth mutation, located in the N-terminal region of
      the protein, specifically affects the cooperativity of DNA binding. This mutation
      reveals the functional importance of a putative Cys2/Cys2 zinc finger motif of a
      novel type, located outside the DNA binding domain. A systematic deletion
      analysis shows that interaction between this proposed Cys2/Cys2 motif and a
      classical Cys2/His2 zinc finger mediates homodimerization, which is required for
      DNA binding cooperativity.

PMID- 9154813
TI  - Cytoplasmic p53 polypeptide is associated with ribosomes.
AB  - Our previous finding that the tumor suppressor p53 is covalently linked to 5.8S
      rRNA suggested functional association of p53 polypeptide with ribosomes. p53
      polypeptide is expressed at low basal levels in the cytoplasm of normal growing
      cells in the G1 phase of the cell cycle. We report here that cytoplasmic wild
      type p53 polypeptide from both rat embryo fibroblasts and MCF7 cells and the
      A135V transforming mutant p53 polypeptide were found associated with ribosomes to
      various extents. Treatment of cytoplasmic extracts with RNase or puromycin in the
      presence of high salt, both of which are known to disrupt ribosomal function,
      dissociated p53 polypeptide from the ribosomes. In immunoprecipitates of p53
      polypeptide-associated ribosomes, 5.8S rRNA was detectable only after proteinase
      K treatment, indicating all of the 5.8S rRNA in p53-associated ribosomes is
      covalently linked to protein. While 5.8S rRNA linked to protein was found in the
      immunoprecipitates of either wild-type or A135V mutant p53 polypeptide associated
      with ribosomes, little 5.8S rRNA was found in the immunoprecipitates of the
      slowly sedimenting p53 polypeptide, which was not associated with ribosomes. In
      contrast, 5.8S rRNA was liberated from bulk ribosomes by 1% sodium dodecyl
      sulfate, without digestion with proteinase K, indicating that these ribosomes
      contain 5.8S rRNA, which is not linked to protein. Immunoprecipitation of p53
      polypeptide coprecipitated a small fraction of ribosomes. p53 mRNA
      immunoprecipitated with cytoplasmic p53 polypeptide, while GAPDH mRNA did not.
      These results show that cytoplasmic p53 polypeptide is associated with a subset
      of ribosomes, having covalently modified 5.8S rRNA.

PMID- 9154814
TI  - neu/ERBB2 cooperates with p53-172H during mammary tumorigenesis in transgenic
      mice.
AB  - Thirty percent of human breast cancers have amplification of ERBB2, often in
      conjunction with mutations in p53. The most common p53 mutation in human breast
      cancers is an Arg-to-His mutation at codon 175, an allele that functions in a
      dominant oncogenic manner in tumorigenesis assays and is thus distinct from loss
      of p53. Transgenic mice expressing mouse mammary tumor virus-driven neu transgene
      (MMTV-neu) develop clonal mammary tumors with a latency of 234 days, suggesting
      that other events are necessary for tumor development. We have examined the role
      of mutations in p53 in tumor development in these mice. We have found that 37% of
      tumors arising in these mice have a missense mutations in p53. We have directly
      tested for cooperativity between neu and mutant p53 in mammary tumorigenesis by
      creating bitransgenic mice carrying MMTV-neu and 172Arg-to-His p53 mutant (p53
      172H). In these bitransgenic mice, tumor latency is shortened to 154 days,
      indicating strong cooperativity. None of the nontransgenic mice or the p53-172H
      transgenic mice developed tumors within this time period. Tumors arising in the
      p53-172H/neu bitransgenic mice were anaplastic and aneuploid and exhibited
      increased apoptosis, in distinction to tumors arising in p53-null mice, in which
      apoptosis is diminished. Further experiments address potential mechanisms of
      cooperativity between the two transgenes. In these bitransgenic mice, we have
      recapitulated two common genetic lesions that occur in human breast cancer and
      have shown that p53 mutation is an important cooperating event in neu-mediated
      oncogenesis.

PMID- 9154815
TI  - Overexpression of human release factor 1 alone has an antisuppressor effect in
      human cells.
AB  - Two eukaryotic proteins involved in translation termination have recently been
      characterized in in vitro experiments. Eukaryotic release factor 1 (eRF1)
      catalyzes the release of the polypeptide chain without any stop codon
      specificity. The GTP-binding protein eRF3 confers GTP dependence to the
      termination process and stimulates eRF1 activity. We used tRNA-mediated nonsense
      suppression at different stop codons in a cat reporter gene to analyze the
      polypeptide chain release factor activities of the human eRF1 and eRF3 proteins
      overexpressed in human cells. In a chloramphenicol acetyltransferase assay, we
      measured the competition between the suppressor tRNA and the human release
      factors when a stop codon was present in the ribosomal A site. Whatever the stop
      codon (UAA, UAG, or UGA) present in the cat open reading frame, the
      overexpression of human eRF1 alone markedly decreased translational readthrough
      by suppressor tRNA. Thus, like the procaryotic release factors RF1 and RF2 in
      Escherichia coli, eRF1 seems to have an intrinsic antisuppressor activity in
      human cells. Levels of antisuppression of overexpression of both eRF3 and eRF1
      were almost the same as those of overexpression of eRF1 alone, suggesting that
      eRF1-eRF3 complex-mediated termination may be controlled by the expression level
      of eRF1. Surprisingly, when overexpressed alone, eRF3 had an inhibitory effect on
      cat gene expression. The results of cat mRNA stability studies suggest that eRF3
      inhibits gene expression at the transcriptional level. This indicates that in
      vivo, eRF3 may perform other functions, including the stimulation of eRF1
      activity.

PMID- 9154816
TI  - Prebending the estrogen response element destabilizes binding of the estrogen
      receptor DNA binding domain.
AB  - Binding of many eukaryotic transcription regulatory proteins to their DNA
      recognition sequences results in conformational changes in DNA. To test the
      effect of altering DNA topology by prebending a transcription factor binding
      site, we examined the interaction of the estrogen receptor (ER) DNA binding
      domain (DBD) with prebent estrogen response elements (EREs). When the ERE in
      minicircle DNA was prebent toward the major groove, which is in the same
      direction as the ER-induced DNA bend, there was no significant effect on ER DBD
      binding relative to the linear counterparts. However, when the ERE was bent
      toward the minor groove, in a direction that opposes the ER-induced DNA bend,
      there was a four- to eightfold reduction in ER DBD binding. Since reduced binding
      was also observed with the ERE in nicked circles, the reduction in binding was
      not due to torsional force induced by binding of ER DBD to the prebent ERE in
      covalently closed minicircles. To determine the mechanism responsible for reduced
      binding to the prebent ERE, we examined the effect of prebending the ERE on the
      association and dissociation of the ER DBD. Binding of the ER DBD to ERE
      containing minicircles was rapid when the EREs were prebent toward either the
      major or minor groove of the DNA (k(on) of 9.9 x 10(6) to 1.7 x 10(7) M(-1) s(
      1)). Prebending the ERE toward the minor groove resulted in an increase in k(off)
      of four- to fivefold. Increased dissociation of the ER DBD from the ERE is,
      therefore, the major factor responsible for reduced binding of the ER DBD to an
      ERE prebent toward the minor groove. These data provide the first direct
      demonstration that the interaction of a eukaryotic transcription factor with its
      recognition sequence can be strongly influenced by altering DNA topology through
      prebending the DNA.

PMID- 9154817
TI  - Glucocorticoid receptor-mediated cell cycle arrest is achieved through distinct
      cell-specific transcriptional regulatory mechanisms.
AB  - Glucocorticoids inhibit proliferation of many cell types, but the events leading
      from the activated glucocorticoid receptor (GR) to growth arrest are not
      understood. Ectopic expression and activation of GR in human osteosarcoma cell
      lines U2OS and SAOS2, which lack endogenous receptors, result in a G1 cell cycle
      arrest. GR activation in U2OS cells represses expression of the cyclin-dependent
      kinases (CDKs) CDK4 and CDK6 as well as their regulatory partner, cyclin D3,
      leading to hypophosphorylation of the retinoblastoma protein (Rb). We also
      demonstrate a ligand-dependent reduction in the expression of E2F-1 and c-Myc,
      transcription factors involved in the G1-to-S-phase transition. Mitogen-activated
      protein kinase, CDK2, cyclin E, and the CDK inhibitors (CDIs) p27 and p21 are
      unaffected by receptor activation in U2OS cells. The receptor's N-terminal
      transcriptional activation domain is not required for growth arrest in U2OS
      cells. In Rb-deficient SAOS2 cells, however, the expression of p27 and p21 is
      induced upon receptor activation. Remarkably, in SAOS2 cells that express a GR
      deletion derivative lacking the N-terminal transcriptional activation domain,
      induction of CDI expression is abolished and the cells fail to undergo ligand
      dependent cell cycle arrest. Similarly, murine S49 lymphoma cells, which, like
      SAOS2 cells, lack Rb, require the N-terminal activation domain for growth arrest
      and induce CDI expression upon GR activation. These cell-type-specific
      differences in receptor domains and cellular targets linking GR activation to
      cell cycle machinery suggest two distinct regulatory mechanisms of GR-mediated
      cell cycle arrest: one involving transcriptional repression of G1 cyclins and
      CDKs and the other involving enhanced transcription of CDIs by the activated
      receptor.

PMID- 9154818
TI  - The neuronal RNA binding protein Nova-1 recognizes specific RNA targets in vitro
      and in vivo.
AB  - Nova-1, an autoantigen in paraneoplastic opsoclonus myoclonus ataxia (POMA), a
      disorder associated with breast cancer and motor dysfunction, is a neuron
      specific nuclear RNA binding protein. We have identified in vivo Nova-1 RNA
      ligands by combining affinity-elution-based RNA selection with protein-RNA
      immunoprecipitation. Starting with a pool of approximately 10(15) random 52-mer
      RNAs, we identified long stem-loop RNA ligands that bind to Nova-1 with high
      affinity (Kd of approximately 2 nM). The loop region of these RNAs harbors a
      approximately 15-bp pyrimidine-rich element [UCAU(N)(0-2)]3 which is essential
      for Nova-1 binding. Mutagenesis studies defined the third KH domain of Nova-1 and
      the [UCAU(N)(0-2)]3 element as necessary for in vitro binding. Consensus [UCAU
      (N)(0-2)], elements were identified in two neuronal pre-mRNAs, one encoding the
      inhibitory glycine receptor alpha2 (GlyR alpha2) and a second encoding Nova-1
      itself. Nova-1 protein binds these RNAs with high affinity and specificity in
      vitro, and this binding can be blocked by POMA antisera. Moreover, both Nova-1
      and GlyR alpha2 pre-mRNAs specifically coimmunoprecipitated with Nova-1 protein
      from brain extracts. Thus, Nova-1 functions as a sequence-specific nuclear RNA
      binding protein in vivo; disruption of the specific interaction between Nova-1
      and GlyR alpha2 pre-mRNA may underlie the motor dysfunction seen in POMA.

PMID- 9154819
TI  - The c-Jun-induced transformation process involves complex regulation of tenascin
      C expression.
AB  - In cooperation with an activated ras oncogene, the site-dependent AP-1
      transcription factor c-Jun transforms primary rat embryo fibroblasts (REF).
      Although signal transduction pathways leading to activation of c-Jun proteins
      have been extensively studied, little is known about c-Jun cellular targets. We
      identified c-Jun-upregulated cDNA clones homologous to the tenascin-C gene by
      differential screening of a cDNA library from REF. This tightly regulated gene
      encodes a rare extracellular matrix protein involved in cell attachment and
      migration and in the control of cell growth. Transient overexpression of c-Jun
      induced tenascin-C expression in primary REF and in FR3T3, an established
      fibroblast cell line. Surprisingly, tenascin-C synthesis was repressed after
      stable transformation by c-Jun compared to that in the nontransformed parental
      cells. As assessed by using the tenascin-C (-220 to +79) promoter fragment cloned
      in a reporter construct, the c-Jun-induced transient activation is mediated by
      two binding sites: one GCN4/AP-1-like site, at position -146, and one NF-kappaB
      site, at position -210. Furthermore, as demonstrated by gel shift experiments and
      cotransfections of the reporter plasmid and expression vectors encoding the p65
      subunit of NF-kappaB and c-Jun, the two transcription factors bind and
      synergistically transactivate the tenascin-C promoter. We previously described
      two other extracellular matrix proteins, SPARC and thrombospondin-1, as c-Jun
      targets. Thus, our results strongly suggest that the regulation of the
      extracellular matrix composition plays a central role in c-Jun-induced
      transformation.

PMID- 9154820
TI  - Activation of an enhancer on the syndecan-1 gene is restricted to fibroblast
      growth factor family members in mesenchymal cells.
AB  - Fibroblast growth factors (FGFs) induce a variety of biological effects on
      different cell types. They activate a number of genes, including immediate-early
      genes, such as the transcription factors Fos and Jun, which are also common
      targets for other tyrosine kinase receptor-activating growth factors. Here we
      describe a secondary far-upstream enhancer on the syndecan-1 gene that is
      activated only by members of the FGF family in NIH 3T3 cells, not by other
      receptor tyrosine kinase-activating growth factors (e.g., epidermal growth
      factor, platelet-derived growth factor, insulin-like growth factor, or serum).
      This FGF-inducible response element (FiRE) consists of a 170-bp array of five DNA
      motifs which bind two FGF-inducible Fos-Jun heterodimers, one inducible AP-2
      related protein, a constitutively expressed upstream stimulatory factor, and one
      constitutive 46-kDa transcription factor. Mutational analysis showed that both AP
      1 binding motifs are required, but not sufficient, for FiRE activation. Moreover,
      agents such as 12-O-tetradecanoylphorbol-13-acetate, okadaic acid, or forskolin,
      which are known to activate AP-1 complexes and AP-1-driven promoters, fail to
      activate FiRE. However, FiRE can be activated by the tyrosine kinase phosphatase
      inhibitor orthovanadate. Taken together, this data implies a differential
      activation of growth factor-initiated signaling on AP-1-driven regulatory
      elements.

PMID- 9154821
TI  - ADA1, a novel component of the ADA/GCN5 complex, has broader effects than GCN5,
      ADA2, or ADA3.
AB  - The ADA genes encode factors which are proposed to function as transcriptional
      coactivators. Here we describe the cloning, sequencing, and initial
      characterization of a novel ADA gene, ADA1. Similar to the previously isolated
      ada mutants, ada1 mutants display decreases in transcription from various
      reporters. Furthermore, ADA1 interacts with the other ADAs in the ADA/GCN5
      complex as demonstrated by partial purification of the complex and
      immunoprecipitation experiments. We estimate that the complex has a molecular
      mass of approximately 2 MDa. Previously, it had been demonstrated that ada5
      mutants displayed more severe phenotypic defects than the other ada mutants (G.
      A. Marcus, J. Horiuchi, N. Silverman, and L. Guarente, Mol. Cell. Biol. 16:3197
      3205, 1996; S. M. Roberts and F. Winston, Mol. Cell. Biol. 16:3206-3213, 1996).
      ada1 mutants display defects similar to those of ada5 mutants and different from
      those of the other mutants with respect to promoters affected, inositol
      auxotrophy, and Spt- phenotypes. Thus, the ADAs can be separated into two
      classes, suggesting that the ADA/GCN5 complex may have two separate functions. We
      present a speculative model on the possible roles of the ADA/GCN5 complex.

PMID- 9154823
TI  - Molecular genetic analysis of Rts1p, a B' regulatory subunit of Saccharomyces
      cerevisiae protein phosphatase 2A.
AB  - The Saccharomyces cerevisiae gene RTS1 encodes a protein homologous to a variable
      B-type regulatory subunit of the mammalian heterotrimeric serine/threonine
      protein phosphatase 2A (PP2A). We present evidence showing that Rts1p assembles
      into similar heterotrimeric complexes in yeast. Strains in which RTS1 has been
      disrupted are temperature sensitive (ts) for growth, are hypersensitive to
      ethanol, are unable to grow with glycerol as their only carbon source, and
      accumulate at nonpermissive temperatures predominantly as large-budded cells with
      a 2N DNA content and a nondivided nucleus. This cell cycle arrest can be overcome
      and partial suppression of the ts phenotype of rts1-null cells occurs if the gene
      CLB2, encoding a Cdc28 kinase-associated B-type cyclin, is expressed on a high
      copy-number plasmid. However, CLB2 overexpression has no suppressive effects on
      other aspects of the rts1-null phenotype. Expression of truncated forms of Rts1p
      can also partially suppress the ts phenotype and can fully suppress the inability
      of cells to grow on glycerol and the hypersensitivity of cells to ethanol. By
      contrast, the truncated forms do not suppress the accumulation of large-budded
      cells at high temperatures. Coexpression of truncated Rts1p and high levels of
      Clb2p fully suppresses the ts phenotype, indicating that the inhibition of growth
      of rts1-null cells at high temperatures is due to both stress-related and cell
      cycle-related defects. Genetic analyses show that the role played by Rts1p in
      PP2A regulation is distinctly different from that played by the other known
      variable B regulatory subunit, Cdc55p, a protein recently implicated in
      checkpoint control regulation.

PMID- 9154822
TI  - Inhibition of the Raf-1 kinase by cyclic AMP agonists causes apoptosis of v-abl
      transformed cells.
AB  - Here we investigate the role of the Raf-1 kinase in transformation by the v-abl
      oncogene. Raf-1 can activate a transforming signalling cascade comprising the
      consecutive activation of Mek and extracellular-signal-regulated kinases (Erks).
      In v-abl-transformed cells the endogenous Raf-1 protein was phosphorylated on
      tyrosine and displayed high constitutive kinase activity. The activities of the
      Erks were constitutively elevated in both v-raf- and v-abl-transformed cells. In
      both cell types the activities of Raf-1 and v-raf were almost completely
      suppressed after activation of the cyclic AMP-dependent kinase (protein kinase A
      [PKA]), whereas the v-abl kinase was not affected. Raf inhibition substantially
      diminished the activities of Erks in v-raf-transformed cells but not in v-abl
      transformed cells, indicating that v-abl can activate Erks by a Raf-1-independent
      pathway. PKA activation induced apoptosis in v-abl-transformed cells while
      reverting v-raf transformation without severe cytopathic effects. Overexpression
      of Raf-1 in v-abl-transformed cells partially protected the cells from apoptosis
      induced by PKA activation. In contrast to PKA activators, a Mek inhibitor did not
      induce apoptosis. The diverse biological responses correlated with the status of
      c-myc gene expression. v-abl-transformed cells featured high constitutive levels
      of expression of c-myc, which were not reduced following PKA activation. Myc
      activation has been previously shown to be essential for transformation by
      oncogenic Abl proteins. Using estrogen-regulated c-myc and temperature-sensitive
      Raf-1 mutants, we found that Raf-1 activation could protect cells from c-myc
      induced apoptosis. In conclusion, these results suggest (i) that Raf-1
      participates in v-abl transformation via an Erk-independent pathway by providing
      a survival signal which complements c-myc in transformation, and (ii) that cAMP
      agonists might become useful for the treatment of malignancies where abl
      oncogenes are involved, such as chronic myeloid leukemias.

PMID- 9154824
TI  - Rapamycin destabilizes interleukin-3 mRNA in autocrine tumor cells by a mechanism
      requiring an intact 3' untranslated region.
AB  - We analyzed the effect of rapamycin on autocrine mast cell tumor lines with
      abnormally stable interleukin-3 (IL-3) transcripts due to a defect in mRNA
      degradation. Rapamycin inhibited IL-3 mRNA expression specifically, while
      transcripts of IL-4 and IL-6 were not affected. As indicated by the use of the
      transcriptional inhibitor actinomycin D or by reporter constructs, inhibition was
      posttranscriptional and resulted from destabilization of the mRNA. Transcripts
      from transgenes lacking the AU-rich 3' untranslated region were refractory to
      drug-induced degradation, suggesting that these 3' sequences contain the target
      of the rapamycin effect. Rapamycin did not promote IL-3 mRNA degradation in cells
      of a tumor variant lacking expression of FKBP12, the binding protein of
      rapamycin. Experiments with wortmannin indicated that rapamycin does not act via
      p70S6 kinase. FK-506, another ligand of FKBP12 affecting the phosphatase
      calcineurin, did not antagonize but shared the effect of rapamycin. Our data fit
      a model whereby both FKBP12 and calcineurin target an unknown regulator of IL-3
      mRNA turnover.

PMID- 9154825
TI  - A lesion in the DNA replication initiation factor Mcm10 induces pausing of
      elongation forks through chromosomal replication origins in Saccharomyces
      cerevisiae.
AB  - We describe a new minichromosome maintenance factor, Mcm10, and show that this
      essential protein is involved in the initiation of DNA replication in
      Saccharomyces cerevisiae. The mcm10 mutant has an autonomously replicating
      sequence-specific minichromosome maintenance defect and arrests at the
      nonpermissive temperature with dumbbell morphology and 2C DNA content. Mcm10 is a
      nuclear protein that physically interacts with several members of the MCM2-7
      family of DNA replication initiation factors. Cloning and sequencing of the MCM10
      gene show that it is identical to DNA43, a gene identified independently for its
      putative role in replicating DNA. Two-dimensional DNA gel analysis reveals that
      the mcm10-1 lesion causes a dramatic reduction in DNA replication initiation at
      chromosomal origins, including ORI1 and ORI121. Interestingly, the mcm10-1 lesion
      also causes replication forks to pause during elongation through these same loci.
      This novel phenotype suggests a unique role for the Mcm10 protein in the
      initiation of DNA synthesis at replication origins.

PMID- 9154826
TI  - Evidence that complex formation by Bas1p and Bas2p (Pho2p) unmasks the activation
      function of Bas1p in an adenine-repressible step of ADE gene transcription.
AB  - Bas1p and Bas2p (Pho2p) are Myb-related and homeodomain DNA binding proteins,
      respectively, required for transcription of adenine biosynthetic genes in
      Saccharomyces cerevisiae. The repression of ADE genes in adenine-replete cells
      involves down-regulation of the functions of one or both of these activator
      proteins. A LexA-Bas2p fusion protein was found to activate transcription from a
      lexAop-lacZ reporter independently of both BAS1 function and the adenine levels
      in the medium. In contrast, a LexA-Bas1p fusion activated the lexAop reporter in
      a BAS2-dependent and adenine-regulated fashion. The DNA binding activity of Bas2p
      was not needed for its ability to support activation of the lexAop reporter by
      LexA-Bas1p, indicating that LexA-Bas1p recruits Bas2p to this promoter. The
      activation functions of both authentic Bas1p and LexA-Bas1p were stimulated under
      adenine-repressing conditions by overexpression of Bas2p, suggesting that complex
      formation by these proteins is inhibited in adenine-replete cells. Replacement of
      Asp-617 with Asn in Bas1p or LexA-Bas1p allowed either protein to activate
      transcription under repressing conditions in a manner fully dependent on Bas2p,
      suggesting that this mutation reduces the negative effect of adenine on complex
      formation by Bas1p and Bas2p. Deletions of N-terminal and C-terminal segments
      from the Bas1p moiety of LexA-Bas1p allowed high-level activation by the
      truncated proteins independently of Bas2p and adenine levels in the medium. From
      these results we propose that complex formation between Bas1p and Bas2p unmasks a
      latent activation function in Bas1p as a critical adenine-regulated step in
      transcription of the ADE genes.

PMID- 9154827
TI  - The ts13 mutation in the TAF(II)250 subunit (CCG1) of TFIID directly affects
      transcription of D-type cyclin genes in cells arrested in G1 at the nonpermissive
      temperature.
AB  - The general transcription initiation factor TFIID contains the TATA-binding
      protein (TBP) and TBP-associated factors (TAFs) implicated in the function of
      gene-specific activators. Previous studies have indicated that a hamster cell
      line (ts13) with a point mutation in the TAF(II)250/CCG1 (TAF(II)250) gene shows
      temperature-sensitive expression of a subset of genes and arrests in late G1 at
      39.5 degrees C. Here, we report the identification of cell cycle-specific (G1
      specific) genes that appear to be regulated directly through TAF(II)250 both in
      vivo and in vitro. Transcription rates of several cell cycle-regulatory genes
      were determined by run-on assays in nuclei from ts13 cells grown at permissive
      (33 degrees C) and nonpermissive (39.5 degrees C) temperatures. Temperature
      dependent differences in transcription rates were observed for cyclin A, D1, and
      D3 genes. In transient-transfection assays, the human cyclin D1 promoter fused to
      a luciferase reporter showed a temperature-dependent reduction in activity in
      ts13 cells but not in parental BHK cells. In in vitro assays, upstream sequence
      dependent transcription from the human cyclin D1 promoter was significantly
      reduced in ts13 nuclear extracts preincubated at 30 degrees C but not in
      similarly treated BHK nuclear extracts, and transcription in the ts13 extract was
      restored by addition of an affinity-purified human TFIID. Preincubation of the
      ts13 nuclear extracts did not affect the function of several GAL4-activation
      domain fusion proteins (GAL4-VP16, GAL4-p65, and GAL4-p53) on either the
      adenovirus major late or cyclin D1 core promoter bearing GAL4 sites, further
      indicating that the effect of the TAF(II)250 mutation is both core promoter and
      activator specific.

PMID- 9154828
TI  - Abrogation of interleukin-3 dependence of myeloid cells by the v-src oncogene
      requires SH2 and SH3 domains which specify activation of STATs.
AB  - The v-src oncogene encodes a nonreceptor tyrosine kinase. When this gene was
      expressed in the myeloblastic cell line 32Dcl3, it was found to abrogate
      interleukin-3 (IL-3) dependence of this cell line and to block its ability to
      terminally differentiate into granulocytes in response to granulocyte colony
      stimulating factor (GCSF). In contrast, a highly related tyrosine kinase gene, v
      fgr, fails to render this cell line IL-3 independent for growth or to block its
      ability to undergo terminal differentiation in the presence of GCSF. The active
      structural domains of v-src that are responsible for the abrogation of IL-3
      dependence of myeloid cells and the mechanisms by which v-src transforms these
      cells are at present unclear. To identify the domains in v-src which are
      responsible for this activity, we constructed several chimeric recombinants
      between the v-src and the related Src family member v-fgr by replacing portions
      of v-src with corresponding domains of v-fgr. These chimeric DNAs were
      transfected into 32Dcl3 cells and examined for their abilities to render this
      cell line IL-3 independent. Our results show that only chimeras containing both
      the SH3 and the SH2 domains of v-src were capable of rendering the 32Dcl3 cell
      line IL-3 independent. To understand the possible mechanisms underlying the IL-3
      independent growth of v-src-transformed 32Dcl3 cells, we examined the
      phosphorylation status of JAK-1, JAK-2, and JAK-3 kinases in the v-src- and v-fgr
      transformed 32Dcl3 cells. Our results show that none of the JAK kinases are
      constitutively phosphorylated by v-src or v-fgr. We then examined the
      phosphorylation status of the STAT (signal transducers and activators of
      transcription) family of transcription factors. Our results show that STAT1,
      STAT3, and STAT5 exist in a constitutively phosphorylated state in v-src
      transformed 32Dcl3 cells, while such constitutive phosphorylation is not seen in
      v-fgr-transformed cell lines. Our results also show that STAT3
      coimmunoprecipitates with v-Src, suggesting that the activation of STAT3 occurs
      due to direct association with v-Src. However, STAT1 and STAT5, which also exist
      in a constitutively phosphorylated state in v-src-transformed 32Dcl3 cells, do
      not coimmunoprecipitate with v-Src, suggesting that these proteins either
      interact weakly with v-Src or are phosphorylated by a mechanism distinctive from
      that of STAT3.

PMID- 9154829
TI  - The centromere enhancer mediates centromere activation in Schizosaccharomyces
      pombe.
AB  - The centromere enhancer is a functionally important DNA region within the
      Schizosaccharomyces pombe centromeric K-type repeat. We have previously shown
      that addition of the enhancer and cen2 centromeric central core to a circular
      minichromosome is sufficient to impart appreciable centromere function. A more
      detailed analysis of the enhancer shows that it is dispensable for centromere
      function in a cen1-derived minichromosome containing the central core and the
      remainder of the K-type repeat, indicating that the critical centromeric K-type
      repeat, like the central core, is characterized by functional redundancy. The
      centromeric enhancer is required, however, for a central core-carrying
      minichromosome to exhibit immediate centromere activity when the circular DNA is
      introduced via transformation into S. pombe. This immediate activation is
      probably a consequence of a centromere-targeted epigenetic system that governs
      the chromatin architecture of the region. Moreover, our studies show that two
      entirely different DNA sequences, consisting of elements derived from two native
      centromeres, can display centromere function. An S. pombe CENP-B-like protein,
      Abp1p/Cbp1p, which is required for proper chromosome segregation in vivo, binds
      in vitro to sites within and adjacent to the modular centromere enhancer, as well
      as within the centromeric central cores. These results provide direct evidence in
      fission yeast of a model, similar to one proposed for mammalian systems, whereby
      no specific sequence is necessary for centromere function but certain classes of
      sequences are competent to build the appropriate chromatin foundation upon which
      the centromere/kinetochore can be formed and activated.

PMID- 9154830
TI  - Differential requirements for DNA replication in the activation of mitotic
      checkpoints in Saccharomyces cerevisiae.
AB  - Checkpoints prevent inaccurate chromosome segregation by inhibiting cell division
      when errors in mitotic processes are encountered. We used a temperature-sensitive
      mutation, dbf4, to examine the requirement for DNA replication in establishing
      mitotic checkpoint arrest. We used gamma-irradiation to induce DNA damage and
      hydroxyurea to limit deoxyribonucleotides in cells deprived of DBF4 function to
      investigate the requirement for DNA replication in DNA-responsive checkpoints. In
      the absence of DNA replication, mitosis was not inhibited by these treatments,
      which normally activate the DNA damage and DNA replication checkpoints. Our
      results support a model that indicates that the assembly of replication
      structures is critical for cells to respond to defects in DNA metabolism. We show
      that activating the spindle checkpoint with nocodazole does not require prior
      progression through S phase but does require a stable kinetochore.

PMID- 9154831
TI  - Sfh1p, a component of a novel chromatin-remodeling complex, is required for cell
      cycle progression.
AB  - Several eukaryotic multiprotein complexes, including the Saccharomyces cerevisiae
      Snf/Swi complex, remodel chromatin for transcription. In contrast to the Snf/Swi
      proteins, Sfh1p, a new Snf5p paralog, is essential for viability. The
      evolutionarily conserved domain of Sfh1p is sufficient for normal function, and
      Sfh1p interacts functionally and physically with an essential Snf2p paralog in a
      novel nucleosome-restructuring complex called RSC (for remodels the structure of
      chromatin). A temperature-sensitive sfh1 allele arrests cells in the G2/M phase
      of the cell cycle, and the Sfh1 protein is specifically phosphorylated in the G1
      phase. Together, these results demonstrate a link between chromatin remodeling
      and progression through the cell division cycle, providing genetic clues to
      possible targets for RSC function.

PMID- 9154832
TI  - The absence of the transcription activator TFE3 impairs activation of B cells in
      vivo.
AB  - TFE3 is a ubiquitously expressed member of the TFE3/mi family of basic helix loop
      helix zipper transcription factors. TFE3 binds to muE3 sites located in the
      immunoglobulin heavy-chain (IgH) intronic enhancer, heavy-chain variable region
      promoters, the Ig kappa intronic enhancer, and regulatory sites in other genes.
      To understand the role of TFE3 in Ig expression and lymphoid development, we used
      embryonic stem (ES) cell-mediated gene targeting and RAG2-/- blastocyst
      complementation to generate mice which lack TFE3 in their B and T lymphocytes.
      TFE3- ES cells fully reconstitute the B- and T-cell compartments, giving rise to
      normal patterns of IgM+ B220+ B cells and CD4+ and CD8+ T cells. However, TFE3- B
      cells show several defects consistent with poor B-cell activation. Serum IgM
      levels are reduced twofold and IgG and IgA isotypes are reduced three- to sixfold
      in the TFE3- chimeras even though in vitro, the TFE3- splenocytes secrete normal
      levels of all isotypes in response to lipopolysaccharide activation. Peripheral
      TFE3- B cells also show reduced surface expression of CD23 and CD24 (heat-stable
      antigen).

PMID- 9154833
TI  - A direct contact between the dorsal rel homology domain and Twist may mediate
      transcriptional synergy.
AB  - The establishment of mesoderm and neuroectoderm in the early Drosophila embryo
      relies on interactions between the Dorsal morphogen and basic-helix-loop-helix
      (bHLH) activators. Here we show that Dorsal and the bHLH activator Twist
      synergistically activate transcription in cell culture and in vitro from a
      promoter containing binding sites for both factors. Somewhat surprisingly, a
      region of Twist outside the conserved bHLH domain is required for the synergy. In
      Dorsal, the rel homology domain appears to be sufficient for synergy. Protein
      protein interaction assays show that Twist and Dorsal bind to one another in
      vitro. However, this interaction does not appear to be of sufficient strength to
      yield cooperative binding to DNA. Nonetheless, the regions of Twist and Dorsal
      required for the binding interaction are also required for synergistic
      transcriptional activation.

PMID- 9154834
TI  - Discrete roles of the Spc1 kinase and the Atf1 transcription factor in the UV
      response of Schizosaccharomyces pombe.
AB  - Exposure of mammalian cells to UV irradiation or alkylating agents leads to the
      activation of the c-Jun N-terminal kinase and p38 stress-activated protein kinase
      cascades, phosphorylation of c-Jun and ATF-2 bZIP transcription factors, and
      finally to selective induction of gene expression. This UV response is believed
      to be crucially important for cell survival, although conclusive evidence is
      lacking. Here, we address this issue by investigating a homologous UV response
      pathway in the fission yeast Schizosaccharomyces pombe. In fission yeast cells,
      UV irradiation induces activation of Spc1 stress-activated protein kinase, which
      in turn phosphorylates the Atf1 bZIP transcription factor. spc1 mutants are
      hypersensitive to killing by UV at a level equivalent to some checkpoint rad
      mutants. Whereas checkpoint rad mutants fail to arrest division in response to
      DNA damage, spc1 mutants are defective at resuming cell division after UV
      exposure. Levels of basal and UV-induced transcription of ctt1+, which encodes a
      catalase believed important for combating oxidative stress caused by UV, are
      extremely low in spc1 mutants. Atf1 is required for UV-induced transcription of
      ctt1+, but atf1 mutants are not hypersensitive to killing by UV. This surprising
      finding is explained by the observation that ctt1+ basal expression is unaffected
      in atf1 single mutant and spc1 atf1 double mutant cells, suggesting that
      unphosphorylated Atf1 represses ctt1+ expression in spc1 cells. In fact, the
      level of UV sensitivity of spc1 atf1 double mutant cells is intermediate between
      those of the wild type and spc1 mutants. These findings suggest the following.
      (i) Key properties of UV response mechanisms are remarkably similar in mammals
      and S. pombe. (ii) Activation of Spc1 kinase greatly enhances survival of UV
      irradiated cells. (iii) Induction of gene expression by activation of Atf1 may
      not be the most important mechanism by which stress-activated kinases function in
      the UV response.

PMID- 9154835
TI  - JAK2 is required for induction of the murine DUB-1 gene.
AB  - Cytokine receptors activate multiple signal transduction pathways, resulting in
      the induction of specific target genes. We have recently identified a
      hematopoietic cell-specific immediate-early gene, DUB-1, that encodes a growth
      regulatory deubiquitinating enzyme. The DUB-1 gene contains a 112-bp enhancer
      element that is specifically induced by the beta c subunit of the interleukin-3
      (IL-3) receptor. To investigate the mechanism of DUB-1 induction, we examined the
      effects of dominant-negative forms of JAK kinases, STAT transcription factors,
      and Raf-1 in transient transfection assays. In Ba/F3 cells, IL-3 induced a dose
      dependent activation of DUB-1-luciferase (luc) and GAS-luc reporter constructs. A
      dominant-negative form of JAK2 (truncated at amino acid 829) inhibited the
      induction of DUB-1-luc and GAS-luc by IL-3. A dominant-negative form of STAT5
      (truncated at amino acid 650) inhibited the induction of GAS-luc but not DUB-1
      luc. A dominant-negative form of Raf-1 inhibited the induction of DUB-1-luc but
      had no effect on the induction of GAS-luc by IL-3. The requirement for JAK2 in
      the stimulation of the DUB-1 enhancer was further supported by the suppression of
      DUB-1 induction in Ba/F3 cells stably expressing the dominant-negative JAK2
      polypeptide. We hypothesize that IL-3 activates a JAK2/Raf-1 signaling pathway
      that is required for DUB-1 induction and is independent of STAT5.

PMID- 9154837
TI  - Instability of CAG and CTG trinucleotide repeats in Saccharomyces cerevisiae.
AB  - A quantitative genetic assay was developed to monitor alterations in tract
      lengths of trinucleotide repeat sequences in Saccharomyces cerevisiae. Insertion
      of (CAG)50 or (CTG)50 repeats into a promoter that drives expression of the
      reporter gene ADE8 results in loss of expression and white colony color.
      Contractions within the trinucleotide sequences to repeat lengths of 8 to 38
      restore functional expression of the reporter, leading to red colony color.
      Reporter constructs including (CAG)50 or (CTG)50 repeat sequences were integrated
      into the yeast genome, and the rate of red colony formation was measured. Both
      orientations yielded high rates of instability (4 x 10(-4) to 18 x 10(-4) per
      cell generation). Instability depended on repeat sequences, as a control
      harboring a randomized (C,A,G)50 sequence was at least 100-fold more stable. PCR
      analysis of the trinucleotide repeat region indicated an excellent correlation
      between change in color phenotype and reduction in length of the repeat tracts.
      No preferential product sizes were observed. Strains containing disruptions of
      the mismatch repair gene MSH2, MSH3, or PMS1 or the recombination gene RAD52
      showed little or no difference in rates of instability or distributions of
      products, suggesting that neither mismatch repair nor recombination plays an
      important role in large contractions of trinucleotide repeats in yeast.

PMID- 9154836
TI  - Ribotoxic stress response: activation of the stress-activated protein kinase JNK1
      by inhibitors of the peptidyl transferase reaction and by sequence-specific RNA
      damage to the alpha-sarcin/ricin loop in the 28S rRNA.
AB  - Inhibition of protein synthesis per se does not potentiate the stress-activated
      protein kinases (SAPKs; also known as cJun NH2-terminal kinases [JNKs]). The
      protein synthesis inhibitor anisomycin, however, is a potent activator of
      SAPKs/JNKs. The mechanism of this activation is unknown. We provide evidence that
      in order to activate SAPK/JNK1, anisomycin requires ribosomes that are
      translationally active at the time of contact with the drug, suggesting a
      ribosomal origin of the anisomycin-induced signaling to SAPK/JNK1. In support of
      this notion, we have found that aminohexose pyrimidine nucleoside antibiotics,
      which bind to the same region in the 28S rRNA that is the target site for
      anisomycin, are also potent activators of SAPK/JNK1. Binding of an antibiotic to
      the 28S rRNA interferes with the functioning of the molecule by altering the
      structural interactions of critical regions. We hypothesized, therefore, that
      such alterations in the 28S rRNA may act as recognition signals to activate
      SAPK/JNK1. To test this hypothesis, we made use of two ribotoxic enzymes, ricin A
      chain and alpha-sarcin, both of which catalyze sequence-specific RNA damage in
      the 28S rRNA. Consistent with our hypothesis, ricin A chain and alpha-sarcin were
      strong agonists of SAPK/JNK1 and of its activator SEK1/MKK4 and induced the
      expression of the immediate-early genes c-fos and c-jun. As in the case of
      anisomycin, ribosomes that were active at the time of exposure to ricin A chain
      or alpha-sarcin were able to initiate signal transduction from the damaged 28S
      rRNA to SAPK/JNK1 while inactive ribosomes were not.

PMID- 9154838
TI  - A ubiquitin-conjugating enzyme in fission yeast that is essential for the onset
      of anaphase in mitosis.
AB  - A cDNA encoding a ubiquitin-conjugating enzyme designated UbcP4 in fission yeast
      was isolated. Disruption of its genomic gene revealed that it was essential for
      cell viability. In vivo depletion of the UbcP4 protein demonstrated that it was
      necessary for cell cycle progression at two phases, G2/M and metaphase/anaphase
      transitions. The G2 arrest of UbcP4-depleted cells was dependent upon chk1, which
      mediates checkpoint pathway. UbcP4-depleted cells arrested at metaphase had
      condensed chromosomes but were defective in separation. However, septum formation
      and cytokinesis were not restrained during the metaphase arrest. Overexpression
      of UbcP4 specifically rescued the growth defect of cut9ts cells at a restrictive
      temperature. cut9 encodes a component of the anaphase-promoting complex (APC)
      which is required for chromosome segregation at anaphase and moreover is defined
      as cyclin-specific ubiquitin ligase. Cdc13, a mitotic cyclin in fission yeast,
      was accumulated in the UbcP4-depleted cells. These results strongly suggested
      that UbcP4 is a ubiquitin-conjugating enzyme working in conjunction with APC and
      mediates the ubiquitin pathway for degradation of "sister chromatid holding
      protein(s)" at the onset of anaphase and possibly of mitotic cyclin at the exit
      of mitosis.

PMID- 9154839
TI  - Rok1p is a putative RNA helicase required for rRNA processing.
AB  - The synthesis of ribosomes involves many small nucleolar ribonucleoprotein
      particles (snoRNPs) as transacting factors. Yeast strains lacking the snoRNA,
      snR10, are viable but are impaired in growth and delayed in the early pre-rRNA
      cleavages at sites A0, A1, and A2, which lead to the synthesis of 18S rRNA. The
      same cleavages are inhibited by genetic depletion of the essential snoRNP protein
      Gar1p. Screens for mutations showing synthetic lethality with deletion of the
      SNR10 gene or with a temperature-sensitive gar1 allele both identified the ROK1
      gene, encoding a putative, ATP-dependent RNA helicase of the DEAD-box family. The
      ROK1 gene is essential for viability, and depletion of Rok1p inhibits pre-rRNA
      processing at sites A0, A1, and A2, thereby blocking 18S rRNA synthesis. Indirect
      immunofluorescence by using a ProtA-Rok1p construct shows the protein to be
      predominantly nucleolar. These results suggest that Rok1p is required for the
      function of the snoRNP complex carrying out the early pre-rRNA cleavage
      reactions.

PMID- 9154840
TI  - Plk is a functional homolog of Saccharomyces cerevisiae Cdc5, and elevated Plk
      activity induces multiple septation structures.
AB  - Plk is a mammalian serine/threonine protein kinase whose activity peaks at the
      onset of M phase. It is closely related to other mammalian kinases, Snk, Fnk, and
      Prk, as well as to Xenopus laevis Plx1, Drosophila melanogaster polo,
      Schizosaccharomyces pombe Plo1, and Saccharomyces cerevisiae Cdc5. The M phase of
      the cell cycle is a highly coordinated process which insures the equipartition of
      genetic and cellular materials during cell division. To enable understanding of
      the function of Plk during M phase progression, various Plk mutants were
      generated and expressed in Sf9 cells and budding yeast. In vitro kinase assays
      with Plk immunoprecipitates prepared from Sf9 cells indicate that Glu206 and
      Thr210 play equally important roles for Plk activity and that replacement of
      Thr210 with a negatively charged residue elevates Plk specific activity. Ectopic
      expression of wild-type Plk (Plk WT) complements the cell division defect
      associated with the cdc5-1 mutation in S. cerevisiae. The degree of
      complementation correlates closely with the Plk activity measured in vitro, as it
      is enhanced by a mutationally activated Plk, T210D, but is not observed with the
      inactive forms K82M, D194N, and D194R. In a CDC5 wild-type background, expression
      of Plk WT or T210D, but not of inactive forms, induced a sharp accumulation of
      cells in G1. Consistent with elevated Plk activity, this phenomenon was enhanced
      by the C-terminally deleted forms WT deltaC and T210D deltaC. Expression of T210D
      also induced a class of cells with unusually elongated buds which developed
      multiple septal structures. This was not observed with the C-terminally deleted
      form T210D deltaC, however. It appears that the C terminus of Plk is not required
      for the observed cell cycle influence but may be important for polarized cell
      growth and septal structure formation.

PMID- 9154841
TI  - Tumor promotion by depleting cells of protein kinase C delta.
AB  - Tumor-promoting phorbol esters activate, but then deplete cells of, protein
      kinase C (PKC) with prolonged treatment. It is not known whether phorbol ester
      induced tumor promotion is due to activation or depletion of PKC. In rat
      fibroblasts overexpressing the c-Src proto-oncogene, the phorbol ester 12-O
      tetradecanoylphorbol-13-acetate (TPA) induced anchorage-independent growth and
      other transformation-related phenotypes. The appearance of transformed phenotypes
      induced by TPA in these cells correlated not with activation but rather with
      depletion of expressed PKC isoforms. Consistent with this observation, PKC
      inhibitors also induced transformed phenotypes in c-Src-overexpressing cells.
      Bryostatin 1, which inhibited the TPA-induced down-regulation of the PKCdelta
      isoform specifically, blocked the tumor-promoting effects of TPA, implicating
      PKCdelta as the target of the tumor-promoting phorbol esters. Consistent with
      this hypothesis, expression of a dominant negative PKCdelta mutant in cells
      expressing c-Src caused transformation of these cells, and rottlerin, a protein
      kinase inhibitor with specificity for PKCdelta, like TPA, caused transformation
      of c-Src-overexpressing cells. These data suggest that the tumor-promoting effect
      of phorbol esters is due to depletion of PKCdelta, which has an apparent tumor
      suppressor function.

PMID- 9154842
TI  - Saccharomyces cerevisiae Mpt5p interacts with Sst2p and plays roles in pheromone
      sensitivity and recovery from pheromone arrest.
AB  - SST2 plays an important role in the sensitivity of yeast cells to pheromone and
      in recovery from pheromone-induced G1 arrest. Recently, a family of Sst2p
      homologs that act as GTPase-activating proteins (GAPs) for G alpha subunits has
      been identified. We have identified an interaction between Sst2p and the
      previously identified Mpt5p by using the two-hybrid system. Loss of Mpt5p
      function resulted in a temperature-sensitive growth phenotype, an increase in
      pheromone sensitivity, and a defect in recovery from pheromone-induced G1 arrest,
      although the effects on pheromone response and recovery were mild in comparison
      to those of sst2 mutants. Overexpression of either Sst2p or Mpt5p promoted
      recovery from G1 arrest. Promotion of recovery by overexpression of Mpt5p
      required Sst2p, but the effect of overexpression of Sst2p was only partially
      dependent on Mpt5p. Mpt5p was also found to interact with the mitogen-activated
      protein kinase homologs Fus3p and Kss1p, and an mpt5 mutation was able to
      suppress the pheromone arrest and mating defects of a fus3 mutant. Because either
      mpt5 or cln3 mutations suppressed the fus3 phenotypes, interactions of Mpt5p with
      the G1 cyclins and Cdc28p were tested. An interaction between Mpt5p and Cdc28p
      was detected. We discuss these results with respect to a model in which Sst2p
      plays a role in pheromone sensitivity and recovery that acts through Mpt5p in
      addition to a role as a G alpha GAP suggested by the analysis of the Sst2p
      homologs.

PMID- 9154843
TI  - Translation of the chloroplast psbC mRNA is controlled by interactions between
      its 5' leader and the nuclear loci TBC1 and TBC3 in Chlamydomonas reinhardtii.
AB  - Translation of the chloroplast psbC mRNA in Chlamydomonas reinhardtii has been
      shown previously to require interactions between its 5' untranslated region (5'
      UTR) and the functions encoded by two nuclear loci, which we name here TBC1 and
      TBC2. We show that a 97-nucleotide (nt) region located in the middle of the psbC
      5' UTR is required for translation initiation. Unlike most procaryotic cis-acting
      translational control elements, this region has a translational activation
      function and is located 236 nt upstream from the GUG translation initiation
      codon. In vivo pulse-labeling of chloroplast-encoded proteins and analyses of the
      expression of chimeric reporter genes in vivo reveal that a mutation of a newly
      described locus, TBC3, restores translation from the psbC 5' UTR in the absence
      of either this cis-acting element or the wild-type trans-acting TBC1 function.
      These data demonstrate that sequences located in the middle of the psbC 5' UTR,
      TBC1, and TBC3 functionally interact to control the translation of the psbC mRNA.

PMID- 9154844
TI  - Cdc42 regulates anchorage-independent growth and is necessary for Ras
      transformation.
AB  - The Rho family members Cdc42, Rac, and Rho play a central role in the
      organization of the actin cytoskeleton and regulate transcription. Whereas Rac
      and Rho have been implicated in transformation by oncogenic Ras, the role of
      Cdc42 in this process remains unknown. In this study, we found that Rat1
      fibroblasts expressing constitutively active V12-Cdc42 were anchorage independent
      and proliferated in nude mice but failed to show enhanced growth in low serum.
      Similar to V12-Rac1-expressing Rat1 fibroblasts, V12-Cdc42 lines displayed a high
      frequency of multinucleated cells. Interestingly, coexpression of dominant
      negative N17-Rac1 blocked the V12-Cdc42-induced multinucleated phenotype but not
      growth in soft agar, indicating that Cdc42 controls anchorage independence in a
      Rac-independent fashion. We also showed that dominant negative N17-Cdc42
      inhibited Ras focus formation and anchorage-independent growth and caused
      reversion of the transformed morphology, indicating that Cdc42 is necessary for
      Ras transformation. N17-Cdc42 caused only partial inhibition of Ras-induced low
      serum growth, however. In contrast, whereas N17-Rac1 also effectively inhibited
      Ras-induced anchorage independence, it did not revert the morphology of Ras
      transformed cells. N17-Rac1 strongly inhibited low-serum growth of Ras
      transformed cells, however. Together, these data provide a novel function for
      Cdc42 in cell proliferation and indicate that Cdc42 and Rac play distinct roles
      in growth control and Ras transformation.

PMID- 9154845
TI  - Regulation of microtubule dynamics by Ca2+/calmodulin-dependent kinase IV/Gr
      dependent phosphorylation of oncoprotein 18.
AB  - Oncoprotein 18 (Op18; also termed p19, 19K, p18, prosolin, and stathmin) is a
      regulator of microtubule (MT) dynamics and is phosphorylated by multiple kinase
      systems on four Ser residues. In addition to cell cycle-regulated
      phosphorylation, external signals induce phosphorylation of Op18 on Ser-25 by the
      mitogen-activated protein kinase and on Ser-16 by the Ca2+/calmodulin-dependent
      kinase IV/Gr (CaMK IV/Gr). Here we show that induced expression of a
      constitutively active mutant of CaMK IV/Gr results in phosphorylation of Op18 on
      Ser-16. In parallel, we also observed partial degradation of Op18 and a rapid
      increase of total cellular MTs. These results suggest a link between CaMK IV/Gr,
      Op18, and MT dynamics. To explore such a putative link, we optimized a genetic
      system that allowed conditional coexpression of a series of CaMK IV/Gr and Op18
      derivatives. The result shows that CaMK IV/Gr can suppress the MT-regulating
      activity of Op18 by phosphorylation on Ser-16. In line with these results, by
      employing a chemical cross-linking protocol, it was shown that phosphorylation of
      Ser-16 is involved in weakening of the interactions between Op18 and tubulin.
      Taken together, these data suggest that the mechanism of CaMK IV/Gr-mediated
      suppression of Op18 activity involves both partial degradation of Op18 and direct
      modulation of the MT-destabilizing activity of this protein. These results show
      that Op18 phosphorylation by CaMK IV/Gr may couple alterations of MT dynamics in
      response to external signals that involve Ca2+.

PMID- 9154847
TI  - Rapid diagnostic tests for tuberculosis: progress but no gold standard.

PMID- 9154848
TI  - Sleep fragmentation and daytime wakefulness.

PMID- 9154849
TI  - Sputum in severe exacerbations of asthma: kinetics of inflammatory indices after
      prednisone treatment.
AB  - We have investigated the time-course of symptoms, forced expiratory volume in one
      second (FEV1), and the airway inflammatory changes in sputum selected from saliva
      and blood of 10 patients with severe exacerbation of asthma betwen presentation
      and after 1, 2, 3, 7, and 21 days of treatment. The sputum was induced by a
      modified standard protocol, and we examined its safety. The severe exacerbation
      of asthma was defined by the presence of nocturnal symptoms disturbing sleep
      and/or the need for inhaled short acting beta2-agonist > or = 8 puffs/d and an
      FEV1 after bronchodilator < 60% of predicted. The treatment consisted of
      additional prednisone 30 mg daily for 5 d followed by reduction to zero by day
      10. Abnormal findings [median (interquartile range)] in spontaneous and induced
      sputum included low viability of cells [52.0 (34.0)%]; eosinophilia [20.0
      (16.4)%]; many free eosinophil granules; and increased levels of fluid-phase ECP
      [1960 (9204) microg/L], fibrinogen [6045 (10720) microg/L], and IL-5 [160 (212)
      pg/ml]. Peripheral blood eosinophils [10.4 (7.6)%] and ECP levels [34.0 (35.0)
      microg/L] were increased. After treatment, symptoms, FEV1, blood eosinophilia,
      and serum ECP improved in the first 24 h. Sputum eosinophils and ECP did not
      improve until 48 h and fibrinogen not until 7 d. The improvement in sputum
      eosinophils and ECP levels was correlated with improvement of FEV1 and in fluid
      phase IL-5. Thirty sputum inductions were performed safely in the majority with
      inhaled isotonic or 3% saline (23.3% or 63.3%, respectively) over a short
      duration (mean 8.4 min). The patients who had a fall in FEV1 of > or = 10% (10
      occasions) after induction differed from those with a fall of < 10% only in the
      amount of inhaled beta2-agonist used by the patients in the preceding 24 h [8.0
      (5.0) versus 4.0 (3.0) puffs/d, p = 0.01]. The results suggest that spontaneous
      or induced sputum can be used safely to follow the kinetics of effects of
      antiinflammatory treatment in a severe exacerbation of asthma. The clinical and
      blood indices improve before those in sputum, raising the possibility that
      examination of sputum is a better guide in these patients to follow the effects
      of treatment.

PMID- 9154850
TI  - Influence on asthma morbidity of asthma education programs based on self
      management plans following treatment optimization.
AB  - The objective of this study was to evaluate the effectiveness of an asthma
      education program on morbidity, knowledge, and compliance with inhaled
      corticosteroid treatment using a prospective, randomized, controlled, one-year
      before/one-year-after protocol. After rigorous optimization of asthma therapy
      under the care of respirologists, patients were assigned to one of three groups:
      Group C (control group: no formal education), Group P (education and action plan
      based on peak-flow monitoring), and Group S (education with action plan based on
      monitoring of asthma symptoms). A total of 188 subjects with moderate to severe
      asthma were enrolled and 149 completed the study. Asthma morbidity decreased
      significantly in all groups (p = 0.001). Mean values one-year-before/one-year
      after in Groups C, P, and S were: unscheduled medical visits, 2.4/0.8, 2.3/0.7,
      and 1.9/ 0.7; hospitalizations, 0.21/0.04, 0.24/0.04, and 0.40/0.09; oral steroid
      treatments; 1.3/0.5, 1.2/0.7, and 1.3/0.9; absenteeism from work/school, 9.6/5.2,
      8.8/2.2, and 6.3/2.9. Between-group differences did not reach statistical
      significance (p > 0.05). Asthma knowledge increased in both educated groups
      compared with the control group (p < 0.001) as did short-term compliance with
      inhaled corticosteroids. These results confirm that treatment optimization
      coupled with sustained high quality care in motivated patients can lead to a
      significant decrease in asthma morbidity. In such clinical settings, structured
      asthma education significantly improved short-term compliance with treatment and
      knowledge about asthma, although it could not add extra benefit with regard to
      morbidity. Nevertheless, this study does not refute the potential benefit of
      educational interventions aimed at improving asthma-related morbidity over a
      longer time period or in patients with less optimal care or with high-risk
      factors.

PMID- 9154851
TI  - The immediate and late allergic response to segmental bronchopulmonary
      provocation in asthma.
AB  - The response to antigen is an important factor in the development of airway
      inflammation. Segmental bronchoprovocation (SBP) with antigen and subsequent
      bronchoalveolar lavage (BAL) have provided valuable insight into the mechanisms
      of allergic inflammation. To determine the features of allergic airway response
      in asthma, 19 subjects with mild asthma underwent antigen SBP in a dose-dependent
      manner. The amount of antigen used in SBP was 0 (saline), and 1, 5, or 20% of the
      antigen dose required to drop the FEV1 by 20% (APD20). BAL was done at 5 min and
      48 h after SBP. BAL histamine levels increased modestly 5 min after antigen SBP.
      At 48 h, there was a marked increase in eosinophils and IL-5 concentration even
      in airway segments where the release of histamine was small. Moreover,
      eosinophils correlated with IL-5 levels at 48 h (r = 0.63; p < 0.001), but not
      with BAL histamine concentrations at 5 min. GM-CSF levels did not increase after
      antigen SBP and did not correlate with eosinophils. These observations indicate
      that asthmatic subjects can develop a dose-dependent response to antigen SBP that
      is characterized by a modest increase in histamine immediately after antigen
      exposure, and marked eosinophilia, which appears proportionately greater than the
      histamine response and relatively greater than what is seen in allergic
      nonasthmatic subjects. This feature might be important to the eventual
      development of airway inflammation in asthma.

PMID- 9154852
TI  - Elastase contributes to antigen-induced mucociliary dysfunction in ovine airways.
AB  - Antigen-induced bronchoconstriction is associated with impairment of mucociliary
      clearance with a time course that is consistent with the initial influx of
      neutrophils into the airway. In this study we tested the hypothesis that elastase
      released from activated neutrophils contributes to the acute (0 to 6-hr) antigen
      induced mucociliary dysfunction. Tracheal mucous velocity CTMV), an index of
      mucociliary function, was measured with a roentgenographic technique before and
      serially after airway challenge with Ascaris suum antigen alone, or after
      pretreatment with aerosolized alpha1-protease inhibitor (alpha1-PI, 10 mg) or the
      specific neutrophil elastase inhibitor ICI 200,355 (10 mg). Antigen alone
      significantly decreased TMV. Treatment with either alpha1-PI or ICI 200,355,
      given either at 30 min before antigen challenge or 1 h after challenge,
      significantly attenuated the antigen-induced reduction in TMV at 6 h after
      challenge, whereas sheep treated with inactivated alpha1-PI were not protected
      from this antigen-induced event. Inhalation of ovine elastase (obtained from
      stimulated neutrophils) significantly decreased TMV, and this effect was also
      blocked by pretreatment with alpha1-PI. Both alpha1-PI and ICI 200,355 inhibited
      the activity of elastase obtained from stimulated ovine neutrophils. To verify
      that the neutrophil numbers and elastase activity increased in sheep airways
      after antigen challenge, nine animals underwent bronchoalveolar lavage (BAL) at 2
      h and 4 h after instillation of A. summ antigen. Four hours after challenge, the
      number of neutrophils had increased by 50-fold, and free elastase activity in
      lavage fluid had increased. These data indicate that the antigen-induced
      impairment of mucociliary clearance is partly dependent on increased elastase
      activity, and that elastase inhibitors may be useful in protecting against
      mucociliary dysfunction.

PMID- 9154853
TI  - Corticosteroid reversibility in COPD is related to features of asthma.
AB  - Eosinophilic inflammation has been observed in the airways of patients with
      chronic obstructive pulmonary disease (COPD). A subset of patients clinically
      diagnosed as having COPD show a reversibility of airflow obstruction when treated
      with corticosteroids, and may consist of patients with features of asthma
      including reticular basement membrane thickening and eosinophilic inflammation.
      Twenty-five unselected patients clinically diagnosed as having COPD received a
      daily oral dose of 1.5 mg/kg body weight of prednisolone for 15 d to assess the
      relationships between the functional response to corticosteroids and the presence
      of features of asthma. Eosinophilic inflammation was characterized before the
      course of corticosteroid therapy by enumerating eosinophils in peripheral blood,
      bronchoalveolar lavage fluid (BALF), and bronchial biopsies, using EG2 monoclonal
      antibody, and by measurement of eosinophil cationic protein (ECP) in BALF. A
      response to treatment was defined by an increase in FEV1 of at least 12% from
      baseline values and an absolute value of 200 ml measured at the end of the
      treatment. Twelve of 25 patients responded to the treatment. By comparison with
      nonresponders, responders had a significantly larger number of eosinophils (p <
      0.015), and higher levels of ECP (p = 0.013) in their BALF. The responders had a
      thicker reticular basement membrane than the nonresponders (p < 0.04). These
      results indicate that a response to prednisolone in patients diagnosed as having
      COPD might occur more readily in a subset of patients presenting with features of
      asthma.

PMID- 9154854
TI  - Role of the thermic effect of food in malnutrition of patients with chronic
      obstructive pulmonary disease.
AB  - Malnutrition in patients with chronic obstructive pulmonary disease (COPD) is
      classically ascribed to an increased resting energy expenditure (REE) secondary
      to high cost of breathing. However, malnutrition correlates only weakly with the
      severity of respiratory dysfunction, which suggests other mechanisms. The aim of
      the present study was to determine the possible role of diet-induced
      thermogenesis (DIT). Therefore, we evaluated the relationship between DIT and
      nutritional status, in particular fat-free mass (FFM) estimated by bioelectrical
      impedance analysis in 26 patients with stable COPD (mean FEV1 +/- SEM = 36.5 +/-
      3.8% of predicted). Ten patients were undernourished (weight < 90% of ideal body
      weight [IBW] and/or FFM < 69% of IBW), and 16 were normally nourished. Diet
      induced thermogenesis was determined by comparing postprandial energy expenditure
      and REE, the latter being measured after an overnight fast and the former over 4
      h after a mixed test meal of 0.4 times REE load. No statistical difference in DIT
      was found between undernourished and eutrophic patients. There was no
      relationship between DIT and nutritional or functional parameters, notably FFM.
      These results suggest that malnutrition is not a consequence of an increased DIT.

PMID- 9154855
TI  - Physiologic benefits of exercise training in rehabilitation of patients with
      severe chronic obstructive pulmonary disease.
AB  - We determined the effect on exercise tolerance and physiological exercise
      responses of rigorous rehabilitative exercise training in chronic obstructive
      pulmonary disease (COPD). Fifteen men and 10 women (mean age, 68 +/- 6 yr; FEV1,
      0.93 +/- 0.27 L) participated in a rehabilitation program with an exercise
      component of three per week 45-min sessions of cycle ergometer training for 6 wk
      with exercise intensity kept near maximal targets. Before and after
      rehabilitation, patients performed an incremental test and a constant work rate
      (CWR) test at 80% of the peak work rate in the preprogram incremental test.
      Ventilation (V(E)) and gas exchange were measured breath by breath; arterialized
      venous blood was analyzed for blood gas determinations and lactate.
      Rehabilitation yielded an average increase in peak work rate in the incremental
      test of 36% (p < 0.001), and in the duration of the CWR test of 77% (p < 0.001).
      In the CWR test, the kinetics of O2 uptake, CO2 output, V(E), and heart rate were
      markedly slower than those of healthy subjects. After training, mean response
      time decrease averaged 17, 22, 34, and 29%, respectively (p < 0.02), evidence of
      a physiologic training effect. Further, for identical CWR tasks, V(E) was 10%
      lower (p < 0.02) after training, attributable to altered breathing pattern: tidal
      volume increased by 8% and respiratory rate decreased by 19%, yielding lower V(D)
      /V(T) (0.46 versus 0.53 p < 0.005). Rigorous exercise training for patients with
      severe COPD yields more efficient exercise breathing pattern and lower V(E); this
      is associated with improved exercise tolerance.

PMID- 9154856
TI  - Effect of chest wall vibration on dyspnea during hypercapnia and exercise in
      chronic obstructive pulmonary disease.
AB  - Vibration of chest wall inspiratory muscles during inspiration (in-phase) reduces
      breathlessness associated with hypercapnia and resistive loading in normal
      subjects and in patients with chronic obstructive pulmonary disease (COPD) at
      rest. To evaluate further the effect of chest wall vibration on breathlessness
      ("breathing discomfort") in patients, we studied 10 subjects 52 to 79 yr of age
      with severe dyspnea (mean FEV1, 0.75 L, 27% predicted). On a single day, we used
      two separate stimuli to produce mild to moderate breathlessness (BR): Protocol 1,
      steady-state hypercapnia; Protocol 2, exercise with a lower extremity ergometer.
      During each protocol, we applied in-phase chest wall vibration (CW) randomly
      alternating with one of two controls: deltoid vibration (DV) or no vibration
      (NV). During hypercapnia, CW significantly reduced BR (DV, 2.9 +/- 2.1; CW, 2.3
      +/- 1.4; p < 0.05; NV, 3.3 +/- 2.1; CW, 2.6 +/- 2.0; p < 0.01) without
      significant changes in ventilation. During exercise, CW did not significantly
      alter BR relative to controls. These findings may be explained by the effect of
      vibration on the sense of respiratory effort and/or by improvement of the match
      between efferent motor commands and afferent information from the respiratory
      system. The lack of effect during exercise on BR suggests there may be a
      "therapeutic window" or range of conditions within which CW is effective in
      reducing dyspnea in patients with COPD.

PMID- 9154857
TI  - The contractile properties of the elderly human diaphragm.
AB  - It has previously been reported that aging is associated with a substantial
      decrease in diaphragm strength. To test this hypothesis we studied 15 (10 male, 5
      female) subjects with a mean age of 29 (range 21 to 40) and 15 elderly (10 male,
      5 female) subjects, mean age 73 (range 67 to 81). We measured transdiaphragmatic
      pressure (Pdi) during a maximal sniff (Sniff Pdi) and during bilateral cervical
      magnetic stimulation (CMS) of the phrenic nerve roots (Tw Pdi). Additionally in
      17 subjects (9 elderly and 8 young) the Pdi elicited by paired CMS (pTw Pdi) was
      obtained at interstimulus intervals ranging from 10 to 999 ms (1 to 100 Hz).
      There was considerable overlap between groups. Mean Sniff Pdi in the elderly was
      119 cm H2O compared with 136 cm H2O for the young subjects; this represented a
      median reduction of 18 cm H2O or 13% (p = 0.05, 95% Cl of difference 0 to 33 cm
      H2O). Mean Twitch Pdi in the elderly was 26.8 cm H2O compared with 35.2 cm H2O, a
      median reduction of 8 cm H2O or 23% (p = 0.004, 95% Cl 3 to 13 cm H2O). At 10 Hz
      the elderly tended to generate a higher fraction of the Pdi obtained at 100 Hz
      than the young, but this trend did not achieve statistical significance (p =
      0.11). We conclude that aging is associated with a reduction in diaphragm
      strength. However the magnitude of the reduction is small and may be offset by a
      leftward shift of the force-frequency relationship.

PMID- 9154858
TI  - Cervical magnetic stimulation of the phrenic nerves in bilateral diaphragm
      paralysis.
AB  - Cervical magnetic stimulation (CMS) produces a greater twitch transdiaphragmatic
      pressure (TwPdi) than electrical stimulation. This may be because CMS produces
      rib cage muscle activation, thus producing an inspiratory action independent of
      the diaphragm. Alternatively, CMS could merely stiffen the rib cage, allowing the
      diaphragm to act efficiently, by contracting against a stable rib cage. To
      examine these two hypotheses we studied five patients with isolated bilateral
      diaphragm paralysis using CMS and bilateral electrical phrenic stimulation (BES).
      TwPdi, twitch esophageal pressure (TwPes), and twitch gastric pressure (TwPgas)
      were measured. We also assessed maximal sniff esophageal and transdiaphragmatic
      pressures (SnPes) (SnPdi), maximal inspiratory and expiratory mouth pressures
      (MIP) (MEP), and fall in VC on moving from an upright to a supine position.
      Respiratory muscle strength tests were consistent with bilateral diaphragm
      paralysis, and the MEPs confirmed normal expiratory muscle function. The patients
      were able to generate a mean SnPes of -30 cm H2O, mainly because of inspiratory
      activity of rib cage and neck muscles. However, TwPdi and TwPes during both CMS
      and BES were close to zero. We conclude that in our patients with diaphragm
      paralysis caused by neuralgic amyotrophy, CMS stiffens the rib cage but does not
      have an inspiratory action independent of the diaphragm.

PMID- 9154859
TI  - Ultrasound evaluation of the paralyzed diaphragm.
AB  - Ultrasound has been used to evaluate diaphragm thickness in the zone of
      apposition of the diaphragm to the rib cage. The purpose of this study was to
      determine if ultrasonography could distinguish between a paralyzed and normally
      functioning diaphragm. We predicted that a paralyzed diaphragm would be atrophic
      and not shorten, therefore it would be thin and not thicken during inspiration.
      Thirty subjects (five with bilateral diaphragm paralysis, seven with unilateral
      diaphragm paralysis, three with inspiratory weakness but normally functioning
      diaphragms, and 15 healthy control subjects) had diaphragm ultrasound performed
      with a 7.5 to 10.0 MHz transducer placed over the lower rib cage in the mid
      axillary line. The thickness of the diaphragm (tdi) was measured to the nearest
      0.1 mm at FRC (t(di)FRC) and TLC (t(di)TLC). Diaphragm thickening during
      inspiration (delta t(di)) was calculated as (t(di)TLC - t(di)FRC)/t(di)FRC. In
      patients with unilateral paralysis, t(di) and delta t(di) for the paralyzed
      hemidiaphragm were significantly less than those values for the normally
      functioning hemidiaphragm (1.7 +/- 0.2 mm versus 2.7 +/- 0.5 mm [mean + SD] p <
      0.01 for t(di), and -8.5 +/- 13% versus 65 +/- 26% [p < 0.001] for delta t(di)).
      The t(di) and delta t(di) for patients with bilateral diaphragm paralysis were
      significantly less than those values for the healthy volunteers (1.8 +/- 0.2
      versus 2.8 +/- 0.4 and -1 +/- 15% versus 37 +/- 9% for t(di) and delta t(di),
      respectively) (p < 0.001). We conclude that ultrasound measurements of t(di) and
      delta t(di) can be used to determine if a diaphragm is paralyzed and confirm our
      predictions that a chronically paralyzed diaphragm is atrophic and does not
      thicken during inspiration.

PMID- 9154860
TI  - Relaxation is impaired in the diaphragm muscle of the cardiomyopathic Syrian
      hamster.
AB  - Relaxation was examined in diaphragm muscle strips of cardiomyopathic Syrian
      hamsters and control hamsters. Isotonic lengthening velocity and isometric
      tension decay were analyzed over the load continuum in response to twitch. For
      each load level (P), we measured the maximum extent of shortening (deltaL), the
      peak lengthening velocity (VL), and the peak rate of tension decline (-dP/dtmax).
      The kinetics of sarcomere length (SL) were simultaneously measured by laser
      diffraction. In an attempt to account for the influence of shortening and/or load
      on relaxation, we calculated the slopes of the VL - deltaL and -dP/dtmax - P
      relationships. In both groups, there was a direct relationship between (1) VL and
      deltaL and (2) -dP/dtmax and P. In myopathic hamsters, we observed a decrease in
      the slope of the VL - deltaL relationship (p < 0.05), a decrease in VL at any
      common value of both muscle and sarcomere extent of shortening, and an increase
      in the duration of overall lengthening. Isometric tension decay was significantly
      prolonged in myopathic muscle strips, while the -dP/dtmax - P relationship was
      not significantly different than in controls. At low-to-medium loads, SLs at the
      onset of tension decline were greater in myopathy. These data indicate that
      relaxation of the diaphragm was both slowed and prolonged in myopathic Syrian
      hamsters.

PMID- 9154861
TI  - Intermittent inspiratory muscle training induces fiber hypertrophy in rat
      diaphragm.
AB  - The effects of 8 wk of moderate load intermittent inspiratory resistive loading
      on diaphragm contractility, and histochemistry of the diaphragm, scalenes, and
      gastrocnemius were studied in rats. A resistance was placed in the inspiratory
      port of a Hans-Rudolph valve, through which each animal breathed during 30 min/d,
      5 times/wk (loaded group, n = 10). These rats were compared with animals
      breathing through the same device without inspiratory resistance (control group,
      n = 10). During loading, animals generated mean inspiratory pressures of -3.2 +/-
      1.7 cm H2O with a TI/Ttot of 0.69 +/- 0.06, resulting in a tension-time index of
      0.050. At the end of training, the diaphragm mass increased in loaded animals
      (0.17 +/- 0.01% body mass) compared with control animals (0.15 +/- 0.01%, p <
      0.01), while scalene and gastrocnemius mass remained unchanged. Diaphragmatic
      force as well as fatigue resistance were similar in both groups, whereas time to
      peak tension was significantly (p < 0.01) shorter in loaded rats (18.8 +/- 1.7
      ms) compared with control rats (21.2 +/- 1.8 ms), half-relaxation time remaining
      unchanged. Finally, hypertrophy of diaphragmatic type IIa (+19%, p < 0.01) and
      IIx/b (+12%, p < 0.05) was present in the loaded group. Histochemistry of the
      scalenes remained unchanged, whereas type IIx/b hypertrophy (+12%, p < 0.001) was
      observed in the gastrocnemius internus. We speculate that the latter was due to
      multiple escape maneuvers. We conclude that intermittent inspiratory muscle
      training: (1) caused fast twitch fiber hypertrophy in the diaphragm; (2) did not
      produce any effect in the scalenes.

PMID- 9154862
TI  - Effect of acute hypercapnia on diaphragmatic and limb muscle contractility.
AB  - The purpose of this study was to determine whether acute hypercapnia depresses
      limb muscle and diaphragmatic contractility. Twelve subjects breathed 8% CO2 for
      20 min on two separate occasions. On one occasion, twitch transdiaphragmatic
      pressure (Pdi) was obtained during both cervical magnetic and transcutaneous
      stimulation before and 2, 10, and 30 min after CO2 breathing. In addition, twitch
      Pdi was obtained during CO2 breathing in five subjects using cervical magnetic
      stimulation. On the other occasion, adductor pollicis twitch force was measured
      during transcutaneous supramaximal ulnar nerve stimulation and arterialized
      venous blood gas determinations were obtained before, during, and after CO2
      breathing. Twitch Pdi was not significantly different from baseline at any time
      after CO2 breathing. Similarly, twitch Pdi did not significantly change from the
      beginning to the end of the period of CO2 breathing. In contrast, adductor
      pollicis twitch force was significantly less than baseline 2 min after CO2
      breathing (p < 0.01). Furthermore, during CO2 breathing, adductor pollicis twitch
      force fell significantly, reaching statistical significance at 8 min, decreasing
      still further by 13 min, and then plateauing. During the final 2 min of CO2
      breathing, adductor pollicis twitch force averaged 86.5 +/- 2.7% of the baseline
      value (p < 0.0007). During CO2 breathing, Pco2 rose to 60.1 +/- 0.5 mm Hg,
      whereas pH fell to 7.27 +/- 0.004 units. Breathing 8% CO2 elicited a moderate
      hyperpnea, and minute ventilation during the final minute of CO2 breathing
      averaged 54.74 +/- 4.90 L/min. To ensure that this hyperpnea did not augment
      diaphragmatic activity enough to potentiate the twitch, five subjects voluntarily
      mimicked their CO2 hyperpnea on a separate occasion. Twitch Pdi was not
      significantly different from baseline at any time after voluntary mimicking. To
      ensure that changes in diaphragmatic contractility were not missed by our twitch
      measurements, Pdi was measured during bilateral transcutaneous phrenic nerve
      stimulation at 10 Hz in four subjects. Again, Pdi during 10 Hz stimulation was
      not significantly different from baseline at any time after CO2 breathing. In
      conclusion, (1) acute moderate hypercapnia mildly depresses limb muscle
      contractility, and (2) acute moderate hypercapnia did not produce significant
      changes in diaphragmatic contractility.

PMID- 9154863
TI  - The effect of nonvisible sleep fragmentation on daytime function.
AB  - Patients with sleep apnea/hypopnea syndrome (SAHS) suffer from impaired daytime
      function that correlates with hypoxemia and visible electroencephalographic (EEG)
      arousals. However, not all breathing irregularities during sleep terminate with
      visible EEG arousal. We hypothesized that sleep disturbance without visible EEG
      change may impair daytime function. Twelve normal subjects spent two pairs of 2
      nights each in the laboratory. The first night of each pair was for
      acclimatization. On the second night, subjects either slept undisturbed or had
      sleep fragmented every minute to cause a transient increase in arterial blood
      pressure or increase in heart rate without visible EEG arousal. We tested daytime
      function after each study night. We presented 253 +/- 23 tones (mean +/- SD), 79
      +/- 7% of which did not cause visible EEG arousals. Fragmentation did not alter
      total sleep time (undisturbed: 419 +/- 27 min; fragmented: 414 +/- 32 min; p =
      0.5) or arousal frequency (undisturbed: 22 +/- 4/h; fragmented: 25 +/- 6/h; p =
      0.4). Fragmentation reduced slow-wave sleep (undisturbed: 24 +/- 5%; fragmented:
      20 +/- 4%; p < 0.01), mean sleep onset latency on the multiple sleep latency test
      (MSLT) (undisturbed: 8.0 +/- 3.1; fragmented: 6.2 +/- 2.1 min; p = 0.01) and the
      maintenance of wakefulness test (MWT) (undisturbed: 29.0 +/- 10.0 min; fragmented
      25.7 +/- 9.7 min; p = 0.04). Fragmentation decreased hedonic tone at 7 A.M. (27
      +/- 4, 25 +/- 6; p = 0.03). Nonvisible (autonomic) sleep fragmentation makes
      normal subjects sleepier and impairs their mood.

PMID- 9154864
TI  - Impaired respiratory response to resistive loading during sleep in healthy
      offspring of patients with obstructive sleep apnea.
AB  - To evaluate the possibility that healthy offspring of patients with obstructive
      sleep apnea syndrome (OSAS) may have covert signs of sleep disordered breathing,
      we compared the respiratory response to inspiratory resistive loads (IRL) in 10
      adult offspring of fathers previously diagnosed with OSAS with that of 14
      offspring of healthy parents. None of the offspring in either group had any sign
      of OSAS, and groups were age, weight, and body mass index matched. Both
      ventilatory response to progressively increasing levels of IRL and the IRL
      required to produce severe hypopnea (tidal volume [V(T)] < 20% of unloaded
      magnitude) were determined, during NREM sleep. Offspring of patients with OSAS
      (OSAS offspring) responded to all levels of IRL with greater decreases in V(T).
      Their V(T) decreased in the second breath on IRL of 23 cm H2O/l/s by 39 +/- 10%,
      as compared with a decrease of 19 +/- 4% (mean +/- SD) in the control group (p <
      0.05). Severe hypopnea occurred in the OSAS offspring in response to smaller IRL
      compared to controls (79 +/- 20 and 153 +/- 14 cm H2O/l/s, respectively, p <
      0.005). Total upper airway occlusion in response to IRL occurred in three of the
      OSAS offspring, but in none of the controls. We conclude that apparently healthy
      offspring of patients with OSAS may inherit subtle defects that reduce their
      ability to compensate for increased loads and maintain upper airway patency
      during sleep. We speculate that offspring of OSAS patients with decreased
      tolerance to IRL may be prone to developing OSAS later on in life.

PMID- 9154865
TI  - Effect of obstructive sleep apnea versus sleep fragmentation on responses to
      airway occlusion.
AB  - Although the acute physiologic responses to apnea in patients with obstructive
      sleep apnea (OSA) have been well documented, the changes in these responses over
      the course of the disease have not been investigated. The purpose of this study
      was to use a canine model of OSA to examine the long-term effects of sleep apnea
      on the acute responses to airway occlusion during sleep. Four dogs were studied
      during a control period before induction of OSA, during a period of OSA (83-133
      d), and following cessation of OSA. At least 6 mo after completion of the OSA
      protocol, the dogs were re-studied on a sleep fragmentation protocol (30-60 d) to
      determine the impact of a similar degree of sleep disruption, without OSA, on the
      acute responses to airway occlusion. OSA and sleep fragmentation both resulted in
      lengthening of the time to arousal in response to acute airway occlusion (p <
      0.02) and in greater arterial oxygen desaturation (p < 0.05), peak inspiratory
      pressures (p < 0.003), and surges in maximum systolic and diastolic blood
      pressure during airway occlusion (p < 0.01). There were no differences between
      the changes observed during OSA and during sleep fragmentation. We conclude that
      the changes in the acute responses to airway occlusion resulting from OSA are
      primarily the result of the associated sleep fragmentation.

PMID- 9154866
TI  - Does transfusion practice affect mortality in critically ill patients?
      Transfusion Requirements in Critical Care (TRICC) Investigators and the Canadian
      Critical Care Trials Group.
AB  - In 4,470 critically ill patients, we examined the impact of transfusion practice
      on mortality rates. As compared with survivors, patients who died in intensive
      care units (ICU) had lower hemoglobin values (95 +/- 26 versus 104 +/- 23 g/L, p
      < 0.0001) and were transfused red cells more frequently (42.6% versus 28.0%, p <
      0.0001). In patients with cardiac disease, there was a trend toward an increased
      mortality when hemoglobin values were < 95 g/L (55% versus 42%, p = 0.09) as
      compared with anemic patients with other diagnoses. Patients with anemia, a high
      APACHE II score (> 20), and a cardiac diagnosis had a significantly lower
      mortality rate when given 1 to 3 or 4 to 6 units of allogeneic red cells (55% [no
      transfusions] versus 35% [1 to 3 units] or 32% [4 to 6 units], respectively, p =
      0.01). Adjusted odds ratio (OR) predicting survival were 0.61 (95% CI; 0.37 to
      1.00, p = 0.026) after 1 to 3 units and 0.49 (95% CI; 0.23 to 1.03, p = 0.03)
      after 4 to 6 units compared with nontransfused anemic patients. In the subgroup
      with cardiac disease, increasing hemoglobin values in anemic patients was
      associated with improved survival (OR = 0.80 for each 10 g/L increase, p =
      0.012). We conclude that anemia increases the risk of death in critically ill
      patients with cardiac disease. Blood transfusions appear to decrease this risk.

PMID- 9154867
TI  - Mepacrine decreases lung leak in rats given interleukin-1 intratracheally.
AB  - We hypothesized that phospholipase A2 (PLA2) metabolites contribute to the acute,
      neutrophil-dependent, edematous lung leak that develops after administration of
      interleukin-1 (IL-1) intratracheally to rats and tested this premise by using
      mepacrine to inhibit PLA2 activity in vivo. We found that lung PLA2 activity,
      lung lavage phospholipid content, lung leak index, lung weight gain, and lung
      lavage protein concentrations were increased in rats given IL-1 intratracheally
      compared with sham-treated control rats. By comparison, lungs of mecaprine and IL
      1-treated rats had decreased PLA2 activity, lavage phospholipid content, leak,
      weight gain, and lavage protein increases compared with rats given IL-1
      intratracheally. Mepacrine treatment also decreased lung neutrophil accumulation,
      but not lung lavage cytokine-induced neutrophil chemoattractant (CINC) levels, in
      rats given IL-1 intratracheally. In parallel experiments, mepacrine treatment
      reduced the adhesion of human neutrophils to IL-1-treated human umbilical vein
      endothelial cells in vitro. Our results indicate that PLA2 activity participates
      in the lung neutrophil retention and pulmonary vascular leak that develops in
      rats given IL-1 intratracheally.

PMID- 9154868
TI  - Pressure-volume curves in acute respiratory failure: automated low flow inflation
      versus occlusion.
AB  - Pressure-volume (P-V) curves of the respiratory system allow determination of
      compliance and lower and upper inflection points (LIP and UIP, respectively). To
      minimize lung trauma in mechanical ventilation the tidal volume should be limited
      to the P-V range between LIP and UIP. An automated low flow inflation (ALFI)
      technique, using a computer-controlled Servo Ventilator 900C, was compared with a
      more conventional technique using a series of about 20 different inflated volumes
      (Pst-V curve). The pressure in the distal lung (Pdist) was calculated by
      subtraction of resistive pressure drop in connecting tubes and airways.
      Compliance (Cdist), Pdist(LIP), and Pdist(UIP) were derived from the Pdist-V
      curve and compared with Cst, Pst(LIP), and Pst(UIP) derived from the Pst-V curve.
      Nineteen sedated, paralyzed patients (10 with ARDS and 9 with ARF) were studied.
      We found: Cdist = 2.3 + 0.98 x Cst ml/cm H2O (r = 0.98); Pdist(LIP) = 0.013 +
      1.09 x Pst(LIP) cm H2O (r = 0.96). In patients with ARDS: Pdist(UIP) = 4.71 +
      0.84 x Pst(UIP) cm H2O (r = 0.94). In ARF, we found differences in UIP between
      the methods, but discrepancies occurred above tidal volumes and had little
      practical importance. They may reflect that Pdist comprises dynamic phenomena
      contributing to pressure in the distal lung at large volumes. Compliance, but not
      LIP and UIP, could be accurately determined without subtraction of resistive
      pressure from the pressure measured in the ventilator. We conclude that ALFI,
      which is fully automated and needing no ventilator disconnection, gives useful
      clinical information.

PMID- 9154869
TI  - Inverse ratio ventilation (I/E = 2/1) in acute respiratory distress syndrome: a
      six-hour controlled study.
AB  - To assess the cardiorespiratory effects of a prolonged application of inverse
      ratio ventilation (IRV), we compared IRV (I/E = 2) with conventional ventilation
      (CV) (I/E = 0.5), applied for 6 h each in a randomized order, with constant tidal
      volume (VT) and total positive end-expiratory pressure (PEEP(tot)) in eight
      patients with acute respiratory distress syndrome (ARDS). After 1 h, IRV resulted
      in a lower peak inspiratory pressure (PIP) (28.2 +/- 1.5 versus 35.6 +/- 1.7 cm
      H2O, p < 0.05), an unchanged plateau pressure, and a higher mean airway pressure
      (MAP) (17.8 +/- 0.8 versus 15.6 +/- 0.5 cm H2O, p < 0.05) than CV. No significant
      difference in Pa(O2) and shunt fraction (QS/QT) was observed (83 +/- 7 mm Hg and
      40 +/- 4% in CV versus 92 +/- 14 mm Hg and 35 +/- 3% in IRV, respectively). The
      Pa(CO2) was lower in IRV (48 +/- 3 versus 55 +/- 5 mm Hg, p < 0.05). Cardiac
      index (CI) and oxygen delivery (D(O2)) were lower in IRV (3.7 +/- 0.4 L/min/m2
      and 500 +/- 61 ml/min/m2 versus 4.6 +/- 0.5 L/min/m2 and 617 +/- 80 ml/min/m2,
      respectively, p = 0.05 for both). Regardless of the considered parameter, no
      significant difference was observed between results after 1, 2, 4, and 6 h in
      each mode. We conclude that IRV at a ratio that results in a significant
      intrinsic PEEP does not improve Pa(O2), enhances CO2 elimination, decreases
      cardiac output (CO), and does not exert any time-dependent effect.

PMID- 9154870
TI  - L-canavanine improves organ function and tissue adenosine triphosphate levels in
      rodent endotoxemia.
AB  - Overproduction of NO by an inducible NO synthase (iNOS) plays a major role in the
      pathophysiology of septic shock, and selective inhibition of iNOS in this setting
      could be of great therapeutic value. In the present study, we evaluated the
      effects of L-canavanine, a selective iNOS inhibitor, in an animal model of septic
      shock, with a particular focus on tissue oxidative metabolism and organ
      functions. Anesthetized rats challenged intravenously with lipopolysacharide
      (LPS) were treated after 1 h by a continuous infusion of either L-canavanine (20
      mg/kg/h; n = 11) or an equivalent volume of saline (2 ml/kg/h; n = 17) given for
      4 h. A third group (sham rats; n = 9) did not receive LPS and was treated with a
      continuous infusion of saline (2 ml/kg/h). At the end of experiments, biopsies
      were taken from the liver, the kidney, and the small intestine for the
      measurement of tissue ATP. LPS induced a progressive fall in blood pressure,
      accompanied by biologic signs of liver and kidney failure, concomitant with a
      marked decrease in tissue ATP stores. L-canavanine largely prevented hypotension
      and significantly increased tissue ATP while reducing the signs of organ
      dysfunction. These effects were associated with a significant improvement in
      survival during the 5 h of study. We conclude that L-canavanine not only reduces
      hypotension in endotoxin shock but also largely prevents the detrimental
      consequences of LPS on tissue oxidative metabolism and major organ functions,
      allowing a decrease in endotoxin lethality.

PMID- 9154871
TI  - Quantification of idiopathic pulmonary fibrosis using computed tomography and
      histology.
AB  - We used computed tomography (CT) and histologic analysis to quantify lung
      structure in idiopathic pulmonary fibrosis (IPF). CT scans were obtained from IPF
      and control patients and lung volumes were estimated from measurements of voxel
      size, and X-ray attenuation values of each voxel. Quantitative estimates of lung
      structure were obtained from biopsies obtained from diseased and normal CT
      regions using stereologic methods. CT density was used to calculate the
      proportion of tissue and air, and this value was used to correct the biopsy
      specimens to the level of inflation during the CT scan. The data show that IPF is
      associated with a reduction in airspace volume with no change in tissue volume or
      weight compared with control lungs. Lung surface area decreased two-thirds (p <
      0.001) and mean parenchymal thickness increased tenfold (p < 0.001). An exudate
      of fluid and cells was present in the airspace of the diseased lung regions and
      the number of inflammatory cells, collagen, and proteoglycans was increased per
      100 g of tissue in IPF. We conclude that IPF reorganized lung tissue content
      causing a loss of airspace and surface area without increasing the total lung
      tissue.

PMID- 9154872
TI  - Functional impairment in lone cryptogenic fibrosing alveolitis and fibrosing
      alveolitis associated with systemic sclerosis: a comparison.
AB  - Lone cryptogenic fibrosing alveolitis (CFA) is histologically identical to
      fibrosing alveolitis associated with systemic sclerosis (FASSc), but it has a
      much worse prognosis after matching for disease severity at presentation. Thin
      section CT scanning (CT) provides a reproducible method of quantifying the
      morphologic extent of fibrosing alveolitis. The aim of this study was to gain
      insights into contrasting pathophysiologic mechanisms in the two diseases by
      comparing patterns of functional impairment after matching for extent of disease
      on CT, demographic factors, smoking history, and concurrent treatment. Patients
      with emphysema on CT (n = 16) and patients with FASSc with overt pulmonary
      hypertension (n = 5) were excluded; 111 patients were studied (CFA, n = 54;
      FASSc, n = 57). Patients with CFA were distinguished by more severe functional
      impairment and more extensive disease on CT (40.1 versus 22.1%, p < 0.00005). On
      multivariate analysis, patients with CFA had greater reduction in arterial P(O2)
      (p < 0.0005), wider AaP(O2) (p < 0.0005), greater oxygen desaturation on maximal
      exercise (p < 0.03), and higher dyspnea scores (p < 0.02) than did patients with
      FASSc after controlling for extent of disease on CT and other covariates.
      Measures of lung volume and gas transfer did not differ independently between CFA
      and FASSc. These findings persisted in subanalyses of patients with limited
      disease, extensive disease, histologic confirmation of fibrosing alveolitis, and
      with the reinclusion of patients with emphysema and pulmonary hypertension. The
      patterns of functional impairment were indicative of more severe ventilation
      perfusion mismatch or anatomic shunting in CFA after adjustment for disease
      extent; we speculate that perfusion of poorly ventilated lung parenchyma in CFA
      occurs through new vessels formed in areas of intense inflammation. This
      mechanism may contribute to the greater mortality of patients with CFA than of
      patients with FASSc because of the deleterious effects of hypoxia on concurrent
      cardiac disease.

PMID- 9154873
TI  - Pentoxifylline in treatment of sarcoidosis.
AB  - The optimal therapy for sarcoidosis remains unclear. Most patients show a short
      term response to corticosteroid therapy, but they have to face the risk of
      significant side effects. Because tumor necrosis factor alpha (TNF) plays a
      critical role in granuloma formation and sustenance as well as in the progression
      of sarcoidosis, we investigated pentoxifylline (POF), which exerts TNF-inhibitory
      activity, as a therapeutic agent in active pulmonary sarcoidosis. Twenty-three
      previously untreated patients with documented disease progression during the
      preceding 3 mo were treated with POF (25 mg/kg daily) and followed for 6 mo of
      therapy. Two patients were lost to follow-up, and three patients discontinued POF
      therapy because of gastrointestinal side effects; 18 patients were thus
      evaluated. Eleven patients improved, seven remained stable and, most importantly,
      none deteriorated. Lung function tests-DL(CO), Pa(O2) and Pa(O2)[exercise]-were
      significantly improved in the patient group as a whole and increased in a highly
      significant manner in those who improved. Three patients with corticosteroid
      resistant disease progression were additionally treated with a combination of
      corticosteroids with POF. In all three patients the combination therapy resulted
      in an immediate complete decrease of disease activity, even after tapering
      prednisone to 7.5 mg daily or tapering off corticosteroids. These promising
      results suggest that POF may improve therapeutic regimens in pulmonary
      sarcoidosis either by sparing or replacing corticosteroids.

PMID- 9154874
TI  - Methacholine responsiveness using the raised volume forced expiration technique
      in infants.
AB  - Infant lung function can be assessed with the tidal volume "squeeze" technique
      or, over an extended volume range, with the newer raised volume forced expiration
      technique (RVFET). We assessed methacholine responsiveness in 11 infants,
      measuring both maximal expiratory flow at functional residual capacity
      (V.max,FRC)with the tidal volume technique, and forced expiratory volume/time
      (FEV(t)) with RVFET. We used a standard methodology for the former. FEV(t) was
      measured by inflating the infant's lungs to 20 cm H2O and forcing expiration
      using a jacket setup to transmit a pressure of 20 cm H2O to the airway. Lung
      function was measured at baseline and after methacholine inhalations, increasing
      from 0.1 g/L to 10 g/L in half log dosage increments (DI). The provocative
      concentrations (PC) of methacholine leading to a 40% fall in V.max,FRC and a 15
      or 20% fall in FEV(t) were calculated. The mean provocative concentration of
      methacholine required to produce a 40% fall in V.max,FRC was less than that
      required to produce a 20% fall in FEV0.5 by 0.39 DI (95% CI, -0.60 to 1.38) and
      less than that required to produce a 20% fall in FEV0.75 by 0.42 DI (95%, CI, 
      0.54 to 1.39). Similarly, the provocative concentration of methacholine required
      to produce a 40% fall in V.max,FRC was less than that required to produce a 15%
      fall in FEV0.5 by 0.14 DI (95% CI, -0.99 to 1.28) or a 15% fall in FEV0.75 by
      0.13 DI (95% CI, -0.80 to 1.08), but the differences were small and not
      significant. Despite these differences the agreement between the two methods was
      good, and bronchoconstriction was not attenuated by the forced inspiration
      delivered by the raised volume maneuver. We conclude that the raised volume
      forced expiration technique is able to detect methacholine-induced
      bronchoconstriction.

PMID- 9154875
TI  - Indications for flexible versus rigid bronchoscopy in children with suspected
      foreign-body aspiration.
AB  - Diagnostic indications for flexible bronchoscopy in the initial investigation of
      children with suspected foreign-body (FB) aspiration have not been evaluated
      prospectively. We prospectively collected history, clinical, and radiologic
      findings at prebronchoscopic examination of all children referred for suspected
      FB aspiration between February 1993 and September 1995. Children with
      asphyxiating FB aspiration, requiring immediate rigid bronchoscopy, were
      excluded. If there was clear evidence of FB aspiration from the physical and
      radiographic findings, rigid bronchoscopy was directly performed. If the evidence
      was not convincing, children underwent diagnostic flexible bronchoscopy under
      local anesthesia. If an FB was found, rigid bronchoscopy was always performed for
      extraction. Eighty-three consecutive children (median age: 24 mo) were included.
      Among 28 who underwent rigid bronchoscopy first, 23 had an FB. Among the 55
      children who underwent flexible bronchoscopy first, 17 had an FB. Predictive
      signs of a bronchial FB were a radiopaque FB, and associated unilaterally
      decreased breath sounds and obstructive emphysema (positive predictive value =
      0.94). We propose the following management algorithm: Rigid bronchoscopy is
      performed first in case of asphyxia, a radiopaque FB, or association of
      unilaterally decreased breath sounds and obstructive emphysema. In any other
      case, flexible bronchoscopy is performed first for diagnostic purposes. If
      applied retrospectively to the 83 children in our study, this algorithm would
      have decreased the negative first rigid bronchoscopy rate to 4%. Flexible
      bronchoscopy is a safe and cost-saving diagnostic procedure in children with
      suspected FB aspiration.

PMID- 9154876
TI  - Effect of antibiotic therapy on nasal nitric oxide concentration in children with
      acute sinusitis.
AB  - Recently, it has been demonstrated that paranasal sinuses are an important site
      of nitric oxide (NO) production in the upper airways. The aim of this study was
      to evaluate the NO nasal concentration in children with acute maxillary sinusitis
      before and after treatment with antibiotic therapy. We performed NO nasal
      measurements in 16 children 4 to 13 yr of age with acute maxillary sinusitis and
      compared values with 16 age- and sex-matched healthy control subjects. The
      diagnosis of acute sinusitis was done by clinical signs and symptoms in addition
      to radiographic examination. NO nasal concentrations were measured by a
      chemiluminescence analyzer. Nasal NO steady state during oral breathing was
      recorded. The mean +/- SEM NO nasal concentration in children with sinusitis was
      70 +/- 8.7 parts per billion (ppb) and increased significantly to 220 +/- 15 ppb
      (p < 0.001) after antibiotic therapy (amoxicillin/clavulanate). NO values after
      recovery from sinusitis were similar to those of healthy control subjects (245 +/
      15 ppb, p = NS). NO nasal measurements were also performed before and after
      antibiotic treatment in nine children 4 to 12 yr of age with symptoms of upper
      respiratory tract infection but no symptoms of sinusitis. In these children NO
      nasal levels were 249 +/- 32 ppb and did not change (p = NS) after antibiotic
      therapy. We conclude that during acute maxillary sinusitis the concentration of
      nasal NO is largely decreased, probably because of an impaired flow of NO from
      the paranasal sinuses, and that NO returns to normal levels after antibiotic
      therapy.

PMID- 9154877
TI  - Relationship between airway ion transport and a mild pulmonary disease mutation
      in CFTR.
AB  - Patients with cystic fibrosis (CF) display defects in airway ion transport, but
      the influence of airway transport phenotype on improved prognosis is not known.
      We studied airway bioelectric properties in five CF patients with the rare A455E
      mutation that is associated with mild pulmonary disease. We also evaluated five
      patients possessing premature truncation mutations (G542X and R553X) for which an
      association with mild pulmonary disease has not been as well established. We
      found no evidence in vivo that a mild lung disease mutation in the CF
      transmembrane regulator gene (CFTR) led to correction or partial correction of:
      (1) unstimulated Cl- secretion; (2) beta-agonist-activated Cl- secretion; (3)
      basal sodium reabsorption; or (4) amiloride-sensitive airway sodium transport.
      Early phase therapeutic trials in CF, including human gene transfer trials, rely
      heavily on improvements in airway potential difference to identify promising
      interventions and an improved prognosis. Based on our findings in a naturally
      occurring group of CF patients with an improved pulmonary prognosis (A455E), one
      can argue that marked clinical benefit might be possible without any improvement
      whatsoever in airway bioelectric phenotype. Moreover, if genetic modifiers exist
      that influence the severity of a particular CFTR mutation (e.g., A455E), these
      may be independent of human airway Cl-secretion in vivo, since we detected
      minimal Cl--secretory responses in patients with A455E.

PMID- 9154878
TI  - Dose-related reversal of acute lung rejection by aerosolized cyclosporine.
AB  - This study evaluated the effectiveness of aerosolized cyclosporine as rescue
      therapy for refractory acute rejection in lung-transplant patients that is
      unresponsive to conventional therapy. Over 2 yr, nine allograft recipients with
      histologic evidence of persistent acute rejection and worsening pulmonary
      function were enrolled. Twenty-two patients with similar degrees of unremitting
      rejection served as historical controls. Aerosolization of cyclosporin A (300 mg
      in 4.8 ml propylene glycol) using an AeroTech II jet nebulizer was instituted
      daily for 12 consecutive days followed by a maintenance regimen of 3 d/wk.
      Cyclosporine and tacrolimus blood and plasma levels were maintained within
      therapeutic ranges throughout this trial. Efficacy was assessed by histologic
      grade of rejection, interleukin-6 (IL-6) mRNA expression by graft bronchoalveolar
      lavage cells, and pulmonary function testing before and during cyclosporine
      therapy. In seven patients, results were correlated to deposition of cyclosporine
      aerosol in the allograft(s) as measured by radioisotopic techniques. At a mean of
      37 d after initiation of aerosolized cyclosporine, graft histology improved in
      eight of the nine patients. Cellular IL-6 mRNA expression decreased significantly
      in seven patients (mean IL-6/actin +/- SD, 40.96 +/- 118 versus 0.33 +/- 0.57 [p
      = 0.038]). Pulmonary function (FEV1), which had decreased posttransplant (over a
      mean of 347 d of observation) from a best value of 1.98 +/- 0.8 L to 1.59 +/- 0.6
      L (p = 0.0077), improved over time (152 d) to a posttransplant value of 1.90 +/-
      0.8 (p = 0.025). In the control subjects, FEV1 inexorably declined over a
      comparable period of observation (best posttransplant value 2.36 +/- 0.86 to 1.32
      +/- 0.53, p < 0.0001). There was a strong correlation between cyclosporine
      deposition in the allograft and improvement in FEV1 (r = 0.900, p < 0.01). Fewer
      cycles of pulsed corticosteroids (1.4 +/- 0.9 versus 0.2 +/- 0.4, p = 0.011) and
      anti-thymocyte globulin 0.8 +/- 0.4 versus 0, p = 0.018) and reduced doses of
      oral prednisone (10.8 +/- 3.1 versus 6.1 +/- 4.2 mg/d, p = 0.026) were observed
      during treatment with aerosolized cyclosporine. Episodes of pneumonia also were
      reduced significantly during aerosol therapy (2.6 versus 0.95 episodes/100 d, p =
      0.029). Nephrotoxicity and hepatotoxicity did not occur, and no patients withdrew
      from the study. Aerosolized cyclosporine appears to be safe and effective therapy
      for refractory acute rejection, but confirmation by a larger, randomized trial is
      necessary. The correlation observed between deposition of cyclosporine aerosol
      and physiologic improvement of lung function suggests that there is a dose
      response relationship between the concentration of cyclosporine in the allograft
      and immunologic tolerance.

PMID- 9154879
TI  - The effects of panresistant bacteria in cystic fibrosis patients on lung
      transplant outcome.
AB  - The number of cystic fibrosis (CF) patients undergoing lung transplant continues
      to rise as long term survival improves. One major contraindication to this
      potentially life-saving intervention is infection with multi-drug-resistant
      bacteria. We undertook this retrospective study in 66 transplanted patients over
      6 yr to determine the influence of panresistant bacteria on transplant outcome.
      The in vitro antibiotic susceptibility pattern of respiratory tract bacteria
      obtained pre- and/or intraoperatively was used to categorize patients into
      panresistant (n = 27) (Burkholderia cepacia, n = 6, and Pseudomonas aeruginosa, n
      = 21) or sensitive (n = 39) groups. Postoperative ventilator days, hospital
      length of stay, and antibiotic days were similar for both groups (p > 0.2). The
      incidence of bacterial bronchitis (28% and 33%, respectively) and pneumonia (28%
      and 38%, respectively) did not differ between these groups (p > 0.2) at 6 mo.
      Likewise, one-year (81% and 83%, respectively) survival was similar for both
      groups (p > 0.2). As expected, panresistant B. cepacia patients had a lower 1-yr
      survival (50% versus 90%, p < 0.05) and had a higher mortality attributable to B.
      cepacia (50% versus 0%, p < 0.01) compared with panresistant P. aeruginosa
      patients. Our results indicate that CF patients infected with panresistant P.
      aeruginosa have similar transplant outcomes as patients with sensitive bacteria
      and should not be excluded from lung transplant based solely on this criterion.

PMID- 9154880
TI  - Bronchiolitis obliterans syndrome in heart-lung transplantation: surveillance
      biopsies.
AB  - Transbronchial biopsies (TBBs) are useful to diagnose acute rejection and
      infection in patients with lung transplants. The value of routine surveillance
      biopsies (S-TBBs) is not known, and such biopsies with a clinical indication are
      not without risk and are expensive. One hundred twenty-six 6-mo survivors of
      heart-lung transplantation (HLT) were studied to determine the effect of stopping
      S-TBBs on the development of bronchiolitis obliterans syndrome (BOS) and
      subsequent survival. Fifty-one received transplants while S-TBB was part of
      routine care (group A), and 75 received transplants after this practice was
      stopped (group B). There was no difference in patient characteristics. Group A
      had shorter graft ischemia (p < 0.01) and longer postoperative ventilation (p <
      0.01). Maintenance immunosuppression was similar, but group A had more steroid
      pulses in the second 6 mo after HLT (p < 0.01). The number of patients free from
      any functional deterioration at 49 to 60 mo after HLT declined to 39% in group A
      and 64% in group B. The risk of developing BOS grade 1 in group A relative to
      group B was 1.63 (95% confidence intervals: 0.96-2.79, p = 0.07). Patient
      survival was similar in the two groups. A total of 86 TBBs were taken in the
      absence of any signs or symptoms and had low diagnostic yield. In summary, there
      was no increased incidence of BOS after stopping S-TBBs.

PMID- 9154881
TI  - Validity of a decision tree for predicting active pulmonary tuberculosis.
AB  - The recent outbreaks of multidrug-resistant strains of M. tuberculosis in health
      care facilities has increased concern over its transmission in health care
      facilities. Isolation has been recommended for all patients suspected to have
      tuberculosis even though the feasibility and the cost of this recommendation can
      be substantial. We have developed a classification tree using clinical and
      radiographic data from 277 isolation episodes in patients admitted between August
      1992 and March 1994 who required isolation for suspicion of tuberculosis. The
      classification tree was developed with a sensitivity and negative predictive
      value of 100% by binary recursive partitioning to predict those patients who are
      unlikely to require isolation. The predictor variables were upper zone disease on
      chest radiograph, a history of fever, weight loss, and CD4 count. The tree was
      validated in a separate cohort of 286 isolation episodes between April 1994 and
      December 1995. In this validation cohort, no erroneous prediction was made of not
      isolating a patient with active pulmonary tuberculosis. The classification tree
      had a sensitivity of 100% (95% confidence interval [CI]: 92.5 to 100%), a
      specificity of 48.1% (95% CI: 43.8 to 52.4%), and a negative predictive value of
      100% (95% CI: 98.5 to 100%). We estimate that the use of the tree could have
      reduced the number of patients requiring isolation by more than 40% without
      increasing the risk of cross infection.

PMID- 9154882
TI  - Trimodality of isoniazid elimination: phenotype and genotype in patients with
      tuberculosis.
AB  - The study was undertaken to show that polymorphic isoniazid elimination in humans
      is trimodal; that the acetylator genotype and eliminator phenotype of the
      individual patient are concordant; and that the differences in the
      pharmacokinetic parameters of fast, intermediate, and slow eliminator subgroups
      are statistically significant. Sixty adult patients of both sexes and of mixed
      race with tuberculosis participated in the trial. The apparent elimination rate
      constant (k, h(-1)) and the area under the isoniazid concentration-time curve
      (AUC, mg/L/h), over the interval 2 to 6 h after oral isoniazid were determined in
      all patients; NAT2 allele composition was determined in 47 patients. Serum INH
      concentrations were determined by HPLC and genotypes by PCR/restriction enzyme
      analysis. Three eliminator phenotypes could be distinguished, and concordance
      between the phenotype and the genotype of the individual could be demonstrated.
      The isoniazid concentration-time profiles of the three eliminator subgroups were
      significantly different (p < 0.05). The NAT2*12A allele, which codes for fast
      acetylation, has a high frequency in the population studied, the intermediate
      acetylator genotype is constituted of codominant fast and slow alleles, and the
      distribution of phenotypes/genotypes in the population is consistent with Hardy
      Weinberg predictions. The therapeutic implications of polymorphic isoniazid
      metabolism are discussed.

PMID- 9154883
TI  - Lack of clinical utility of bronchoalveolar lavage cultures for cytomegalovirus
      in HIV infection.
AB  - This study assessed the presence of cytomegalovirus (CMV) in bronchoalveolar
      lavage (BAL) in three subpopulations of HIV-infected patients and correlated its
      presence with clinical status during 3 mo of follow-up. Nineteen asymptomatic
      volunteers, six patients with CMV retinitis, and 46 patients with acute pulmonary
      symptoms underwent BAL and were assessed for CMV by cytopathology, conventional
      shell vial cultures, and antigen detection. Transbronchial biopsies were also
      obtained when possible and evaluated for histopathologic changes of CMV. All
      patients were followed for approximately 3 mo. Cytomegalovirus was detected in
      BAL in nine of 19 (47%) asymptomatic volunteers, in all six patients with CMV
      retinitis, and in 33 of 46 (72%) patients with pulmonary symptoms. Only one
      symptomatic patient with a positive CMV BAL culture developed clinically
      significant CMV pulmonary disease; this patient developed disseminated CMV and
      died. The only other death occurred in a patient with CMV retinitis who developed
      staphylococcal bacteremia. None of the asymptomatic volunteers or patients with
      CMV retinitis developed evidence of CMV pneumonia or any other organ disease with
      CMV. Cytomegalovirus is frequently detected in BAL from HIV-infected patients
      regardless of their pulmonary symptoms and its presence does not clinically
      predict significant pulmonary morbidity or mortality in 3 mo of follow-up.

PMID- 9154884
TI  - Protective effect of intravenously administered cefuroxime against nosocomial
      pneumonia in patients with structural coma.
AB  - In comatose patients admitted to an ICU, particularly those with head injury, the
      incidence of early onset pneumonia is exceedingly high. We performed an open,
      prospective, randomized, and controlled clinical trial aiming at the reduction of
      the incidence of ventilator-associated pneumonia in head-injured patients and
      patients with stroke requiring mechanical ventilation. One hundred patients were
      included because of head injury or coma caused by medical stroke and with Glasgow
      coma scores < or = 12 and mechanical ventilation > 72 h. Patients eligible for
      the study (n = 50) received cefuroxime intravenously (two 1,500-mg doses 12 h
      apart after intubation) (the cefuroxime group) and 50 patients not receiving
      cefuroxime formed the control group. In the former group patients did not receive
      any other antibiotics before the end-point determination, whereas in the latter,
      17 patients received prophylactic antibiotics as prescribed by the attending
      physician. The global incidence of microbiologically confirmed pneumonia was 37%
      (n = 37); 12 (24%) belonged to the cefuroxime group, and 25 (50%) belonged to the
      control group (p = 0.007). Early-onset pneumonia accounted for 70% of all the
      pneumonia episodes (n = 26), eight (67%) belonging to the cefuroxime group, and
      18 (72%) belonging to the control group (p = 0.02). In the control group, four of
      17 (23%) patients receiving prior antibiotics developed pneumonia, whereas 21 of
      33 (64%) patients who did not receive antibiotics developed pneumonia (p =
      0.016). The multivariate analysis revealed that the duration of mechanical
      ventilation (per each day) was an independent risk factor significantly
      associated to the development of pneumonia. Furthermore, the use of cefuroxime
      and/or prior antibiotics in the control group, before the pneumonia episode, had
      a protective effect against its development. No differences were found with
      regard to mortality and morbidity when comparing the study population with the
      control group. Nevertheless, when comparing patients with pneumonia (from both
      study and control groups) with those without it, there was a decrease in total
      hospital stay (35 +/- 13 versus 25 +/- 14 d, p = 0.048) and ICU stay (20 +/- 11
      versus 11 +/- 7 d, p = 0.001). The study demonstrated that the administration of
      two single high doses 1,500 mg each of cefuroxime after the intubation of
      patients comatose because of head injury or medical stroke is an effective
      prophylactic strategy to decrease the incidence of ventilator-associated
      pneumonia.

PMID- 9154885
TI  - Rifampin preventive therapy for tuberculosis infection: experience with 157
      adolescents.
AB  - For persons infected with Mycobacterium tuberculosis resistant to isoniazid
      (INH), rifampin is recommended for the prevention of active disease. However, the
      adverse effects and acceptability of this preventive therapy are largely
      uncharacterized. We prospectively followed 157 high-school students exposed to,
      and probably infected with, M. tuberculosis strains resistant to INH. All 157
      students were prescribed preventive therapy with rifampin (10 mg/kg up to 600 mg
      daily) for 24 wk. While receiving therapy, 41 (26%) reported one or more adverse
      effects; of these, 18 had therapy interrupted temporarily, two permanently. Four
      (2.5%) had alanine aminotransferase elevations greater than two times the upper
      limit of normal (range, 91 to 161 U/L); of these, one had therapy permanently
      stopped. Six (3.8%) self-discontinued therapy. No student was found to have
      active disease during the 2 yr of the study (exact 95% upper confidence limit,
      2.2). We assumed that without preventive therapy, seven cases of tuberculosis
      would have occurred during these 2 yr. Therefore, we estimated that rifampin had
      a minimum protective effect of 56%. In conclusion, preventive therapy with
      rifampin was well tolerated and well accepted, and it appears effective in
      preventing active tuberculosis.

PMID- 9154886
TI  - Effects of neurokinin depletion on airway inflammation induced by chronic antigen
      exposure.
AB  - We assessed the effects of neurokinin (tachykinin) depletion by capsaicin (CAP)
      treatment on airway inflammation induced by repeated ovalbumin (OA) aerosol
      exposures (twice a week for 4 wk) in guinea pigs. The animals were then
      anesthetized, tracheostomized, mechanically ventilated and challenged with
      ovalbumin aerosol. Maximal values of respiratory system resistance and elastance
      after antigen challenge were significantly lower in capsaicin-treated guinea pigs
      than in intact animals (p < 0.001). Morphometric analysis of noncartilaginous
      airways revealed less intense bronchoconstriction (p < 0.001) and peribronchiolar
      edema (p < 0.001) in capsaicin-treated guinea pigs. Chronic antigen exposure
      resulted in a significant increase in lymphocytes and eosinophils both in
      bronchoalveolar lavage (BAL) fluid and airway wall. Immunohistochemistry with
      monoclonal antibodies revealed that most of the lymphocytes present in airway
      wall were CD4+ T cells. Capsaicin treatment resulted in values of CD4+ T cells in
      airway wall significantly lower than non-capsaicin-treated guinea pigs (p <
      0.005). This difference was not observed in eosinophil recruitment. Our results
      suggest that neurokinin release by sensory nerve terminals results in an
      amplification of the pulmonary inflammatory changes induced by chronic antigen
      exposure. In addition, neurokinins play a role in T-cell recruitment induced by
      chronic allergen exposure.

PMID- 9154887
TI  - Effect of mandibular and tongue protrusion on upper airway size during
      wakefulness.
AB  - Oral appliances for the treatment of obstructive sleep apnea (OSA) produce either
      mandibular or tongue protrusion, and are thought to enlarge the upper airway
      (UA). We used videoendoscopy to measure UA cross-sectional area (CSA) and shape
      in the hypopharynx, oropharynx, and velopharynx during various stages of active
      mandibular and tongue protrusion during wakefulness in 10 patients with OSA and
      nine control subjects. Measurements were made in the supine position at end-tidal
      expiration, and were normalized to the CSA in the normal bite position. Airway
      shape was expressed as the anteroposterior/lateral (AP/L) diameter ratio. There
      were no differences between OSA patients and controls in the effects of
      mandibular and tongue protrusion on UA caliber. Both mandibular and tongue
      protrusion increased CSA in the hypopharynx and oropharynx (p < 0.001), whereas
      only tongue protrusion increased CSA in the velopharynx (p < 0.001). Tongue
      protrusion caused a greater increase in oropharyngeal and velopharyngeal CSA than
      did mandibular protrusion (p < 0.05). Mandibular protrusion caused a greater
      increase in CSA in the hypopharynx than in the oropharynx or velopharynx (p <
      0.05). Obese patients had a larger relative increase in oropharyngeal CSA with
      mandibular and tongue protrusion than did subjects of normal weight. Tongue
      protrusion increased the AP/L diameter ratio in the oropharynx and velopharynx (p
      < 0.001), and mandibular protrusion did so to a lesser extent in the oropharynx
      (p < 0.01), resulting in a more circular airway shape. We conclude that
      mandibular and tongue protrusion increase the CSA and alter the shape of the UA
      during wakefulness.

PMID- 9154888
TI  - Nitric oxide modulates ventilatory responses to hypoxia in the developing rat.
AB  - Nitric oxide (NO) is an important excitatory neurotransmitter in the central
      nervous system. In the adult rat, both selective and nonselective blockers of
      constitutive nitric oxide synthase (NOS) induce marked ventilatory reductions
      during sustained hypoxia, thereby enhancing ventilatory roll-off. Since hypoxic
      ventilatory depression is greater in developing mammals during the late phases of
      hypoxic exposure, we hypothesized that limited NOS activity may play a role in
      the late arm of the ventilatory response. To test our hypothesis, 5-d-, 10-d-,
      and 15-d-old rat pups underwent a 30-min hypoxic challenge (10% O2) before and
      after administration of 100 mg/kg N-nitro-L-arginine methyl ester (L-NAME), a
      competitive NOS inhibitor. Minute ventilation (VE) was measured using whole-body
      plethysmography. In 5-d-old pups, early VE hypoxic responses were enhanced, and
      late VE were similar after administration of L-NAME. In contrast, in 15-d-old
      hypoxic pups, L-NAME administration was associated with smaller early VE
      increments and significantly larger VE reductions when compared with pretreatment
      conditions. The role of central nervous system NO in the development of these
      ventilatory changes was further assessed by Western blots of protein equivalents
      from the nucleus tractus solitarius (NTS), the first central relay for peripheral
      chemoreceptor afferent input, which revealed increasing neuronal NOS expression
      with age. Furthermore, NADPH-diaphorase immunohistochemical staining of neurons
      in the NTS revealed increased positively labeled neuronal populations within
      subnuclei of this structure with advancing postnatal age. Current findings
      suggest that NOS activity mediates both excitatory and inhibitory components of
      the hypoxic ventilatory response. Furthermore, in brainstem respiratory regions,
      NO may play a role in modulating the prominent second phase of the biphasic
      response to hypoxia typically seen in early postnatal life.

PMID- 9154889
TI  - Increased production of the potent oxidant peroxynitrite in the lungs of patients
      with idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology
      characterized by alveolar inflammation, progressive proliferation of septal
      cells, increased production of septal matrix, and loss of lung architecture. The
      process of cellular injury in lung fibrosis is thought to be mediated by oxygen
      radicals produced by infiltrating inflammatory cells. Peroxynitrite is a potent
      oxidant produced by the rapid reaction of nitric oxide (NO) and superoxide. We
      investigated the production of nitrotyrosine, a byproduct of protein nitration by
      peroxynitrite, and the expression of the enzymes responsible for generating NO,
      in lungs of patients with IPF and compared them with lungs of normal control
      subjects. We used immunohistochemistry, histochemistry, and in situ hybridization
      to study the production of nitrotyrosine and the expression of inducible (iNOS)
      and constitutive endothelial (eNOS) nitric oxide synthases in 48 lungs of
      patients with different stages of IPF and 21 normal lungs. In lungs of control
      subjects, there was little expression of iNOS and nitrotyrosine in the airway
      epithelium and alveolar macrophages, and abundant expression of eNOS in the
      airway epithelium and vascular endothelium. By contrast, in lungs of patients
      with IPF, strong expression of nitrotyrosine and NOS was seen in macrophages,
      neutrophils, and alveolar epithelium. A significant increase in the expression of
      these molecules was only seen in lungs of patients with the early to intermediate
      stage of the disease. The active stage of IPF is associated with increased
      inflammatory and alveolar expression of nitrotyrosine and NOS. Increased
      production of NO and peroxynitrite may be responsible for the oxidative damage
      seen in this disease.

PMID- 9154890
TI  - Cigarette smoke induces interleukin-8 release from human bronchial epithelial
      cells.
AB  - Cigarette smoking causes the development of chronic bronchitis and chronic
      obstructive pulmonary disease. We hypothesized that exposure to cigarette smoke
      might initiate release of inflammatory mediators by bronchial epithelial cells.
      To evaluate this, the effect of cigarette smoke extract (CSE) on IL-8 release
      from cultured human bronchial epithelial cells was examined. CSE augmented IL-8
      release from bronchial epithelial cells in a concentration- and time-dependent
      manner. Most of the augmenting activity of CSE on IL-8 release from bronchial
      epithelial cells was lost after volatilization or lyophilization treatment. Two
      major volatile factors in cigarette smoke, acrolein and acetaldehyde, augmented
      IL-8 release. Four cell strains were tested and showed increased IL-8 release in
      response to CSE. In addition, bronchoalveolar lavage was performed on 11
      nonsmokers and 12 smokers. IL-8 concentration was greater in the proximal,
      bronchial samples than in distal, alveolar samples, and IL-8 in BAL from smokers
      was higher than in BAL from nonsmokers. There was a significant correlation
      between IL-8 concentration and neutrophil count in bronchial samples of BAL
      fluid. These data support the hypothesis that exposure to cigarette smoke may
      induce bronchial epithelial cells to release IL-8 and that this may contribute to
      airway inflammation in smokers.

PMID- 9154892
TI  - Immunoglobulin G is associated with surfactant protein A aggregate isolated from
      patients with pulmonary alveolar proteinosis.
AB  - We have previously shown that the purified preparation of surfactant protein A
      (SP-A) isolated from patients with pulmonary alveolar proteinosis (PAP) contains
      a very small amount of immunoglobulin G (IgG). We have recently found that there
      exists an abnormal multimerized form (alveolar proteinosis protein-I, APP-I) in
      SP-As isolated from patients with PAP in addition to normal-sized octadecameric
      APP-II. We examined which of the populations of APP that IgG is associated with.
      The APP was purified by mannose-affinity column followed by gelfiltration over
      Bio Gel A5m after the delipidation with 1-butanol. Analysis by gel filtration
      over Bio Gel A15m showed two elution peaks of APP-I and APP-II. When the
      fractions eluted from the Bio Gel A15m column were coated onto microtiter wells
      and reacted with HRP-labeled antihuman IgG, the elution peak of IgG was
      superimposed on that of APP-I but not on that of APP-II. The immunoblotting
      analysis also revealed that a very small amount of IgG, which could not be
      detected by staining with Coomassie blue or amido black, was associated with APP
      I but not with APP-II or normal SP-A. APP-I bound to nonimmune IgG coated onto
      microtiter wells in a concentration-dependent manner, whereas APP-II, normal
      human SP-A, and rat SP-A exhibited almost no binding to IgG. The results indicate
      an unusual property of SP-A during the diseased state.

PMID- 9154891
TI  - Keratinocyte growth factor increases transalveolar sodium reabsorption in normal
      and injured rat lungs.
AB  - Keratinocyte growth factor (KGF) prevents alpha-naphthylthiourea (ANTU)-induced
      permeability edema ex vivo. To explore the mechanisms in this involved effect, we
      administered KGF (5 mg/kg, intratracheally) 48 h prior to ANTU (50 mg/kg,
      intraperitoneally). Several groups were studied: phosphate-buffered
      saline/dimethylsulfoxide (PBS/DMSO) (vehicles), PBS/ANTU, and KGF/ANTU. At 90 min
      after ANTU injection the lungs were removed, ventilated, and perfused ex vivo for
      180 min. Quantification of fluorescein isothiocyanate (FITC)-labeled dextran in
      bronchoalveolar lavage fluid (BALF) was used to assess alveolar capillary barrier
      permeability. KGF attenuated ANTU-induced edema and blockade of sodium transport,
      with ouabain (10(-3) M) or amiloride (10(-4) M) added ex vivo reversed this
      effect. FITC-dextran was increased in the PBS/ANTU group as compared with the
      PBS/DMSO group, indicating permeability edema. In the KGF/ANTU group, there was
      concentration of BALF FITC-dextran, consistent with permeability edema and
      increased alveolar fluid export. Albumin space measurements showed similar
      increases in permeability in the PBS/ANTU and KGF/ANTU groups. Extravascular lung
      water (measured with radiolabeled erythrocytes) was decreased in the KGF/ANTU
      group. Following KGF pretreatment, uninjured lungs exported more intratracheal
      PBS than normal lungs following terbutaline stimulation ex vivo. In conclusion,
      KGF, through type II alveolar pneumocyte hyperplasia with increased sodium
      potassium-adenosine triphosphatase (Na,K-ATPase) activity, attenuated ANTU
      induced edema formation by potentiating alveolar fluid clearance.

PMID- 9154893
TI  - The effect of inhaled leukotriene B4 in normal and in asthmatic subjects.
AB  - Leukotriene (LT) B4 is a potent leukocyte chemotaxin that increases bronchial
      responsiveness in animal models. In a double-blind, placebo-controlled crossover
      study we examined the effects of LTB4 on lung function, bronchial responsiveness,
      and blood leukocyte counts in six normal subjects and in six subjects with mild
      asthma who inhaled mean +/- SEM doses of 17.6 +/- 3.4 and 18.2 +/- 1.9 microg
      LTB4, respectively, or placebo. There were no significant changes in specific
      airway conductance or bronchial responsiveness in either normal subjects or
      asthmatics for as long as 24 h after inhalation. In the normal subjects, LTB4
      rapidly reduced blood neutrophil counts to 19.8 +/- 6.3% of baseline at 5 min (p
      = 0.0003 compared with placebo), followed by a neutrophilia of 307 +/- 40% of
      baseline at 30 min (p = 0.007). Similar changes occurred in asthmatics, with a
      neutropenia at 5 min (69.6 +/- 5.8%; p = 0.003) and a neutrophilia at 30 min (183
      +/- 17.2%; p = 0.037). The neutrophilia was not sustained in either subject
      group, with values being no different from that of placebo by 6 h. The asthmatics
      had significantly less neutropenia (p = 0.005) and less neutrophilia (p = 0.018)
      than did the normal subjects. Placebo inhalation had no effect on any parameter
      in either group. The smaller neutrophil responses in asthmatics may reflect
      desensitization of blood neutrophils in vivo because of chronic exposure to
      endogenous LTB4.

PMID- 9154894
TI  - Cytokines derived from alveolar macrophages induce fever after bronchoscopy and
      bronchoalveolar lavage.
AB  - As much as one-third of patients develop fever and flu-like symptoms after
      fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) for yet unknown
      reasons. The aim of the present study was to investigate factors mediating these
      side effects. Fifty consecutive patients with various pulmonary diseases who
      underwent FOB without further interventions (n = 30) or combined with BAL (n =
      20) were enrolled. Serum levels of the proinflammatory cytokines IL-1beta, IL-6,
      and TNF-alpha were determined directly prior to (t0), directly after (t1), and 6
      h after (t2) the procedures by ELISA. In parallel, blood cultures were drawn at
      t2. At to and t1, generally only low cytokine concentrations could be detected.
      At t2, however, significant increases of cytokine levels were found. IL-6 and TNF
      alpha were significantly higher in patients after BAL than in patients after FOB.
      Comparing patients who developed fever (n = 12) with those who did not (n = 38),
      irrespective of the endoscopic procedures performed, dramatic increases of all
      three cytokines were detected in febrile patients that were significantly higher
      than in patients without fever. In the FOB group only patients who received local
      anesthesia by prilocaine bolus injection into the airways via the working channel
      of the bronchoscope developed fever and increases of IL-6 and IL-beta, whereas
      patients anaesthetized by inhalation of a prilocaine aerosol remained afebrile
      and had slight IL-6 increases only. There was a highly significant correlation
      between IL-6 values at t2 and the number of BAL alveolar macrophages (r = 0.98).
      All blood cultures remained sterile. These results indicate that fever after FOB
      and BAL is induced by proinflammatory cytokines derived from alveolar macrophages
      activated by instillation of fluid into the airways.

PMID- 9154895
TI  - Short-term ozone exposure upregulates P-selectin in normal human airways.
AB  - Short-term exposure to ambient levels of ozone induces neutrophilic bronchitis.
      To investigate the early events contributing to inflammatory cell recruitment in
      the airways we exposed 12 healthy nonsmoking volunteers to 0.12 ppm ozone or
      filtered air for 2 h on two separate occasions. Spirometry and fiberoptic
      bronchoscopy were performed immediately and at 1.5 h after the two exposures,
      respectively. Total protein, albumin, and total and differential cell counts were
      performed on the bronchial wash and BAL fluid. Bronchial biopsies were embedded
      in glycol methacrylate and immunostained for inflammatory cells, including
      neutrophils, mast cells, total T-cells (CD3), T-cell subset CD8, and leukocyte
      endothelial adhesion molecules, including VCAM-1, ICAM-1, E-selectin, and P
      selectin. No significant changes were observed in FEV1, FVC, or any inflammatory
      indices in the bronchial wash and BAL fluid. In addition, no significant
      differences were seen in inflammatory cell numbers or percentages of vessels
      expressing VCAM-1, E-selectin, or ICAM-1 in the biopsies. The percentage of
      vessels expressing P-selectin increased significantly after ozone exposure: p =
      0.016; median (IQR), 28.76 (26.36-36.94) versus 47.06 (38.14-56.86)%. The
      upregulation of P-selectin could signify an early inflammatory response to ozone
      such as margination and rolling of the neutrophils on the vessel wall prior to
      transendothelial migration.

PMID- 9154896
TI  - Rapid diagnostic tests for tuberculosis: what is the appropriate use? American
      Thoracic Society Workshop.
AB  - Recent technologic developments have introduced a number of improvements in the
      ability of clinical laboratories to cultivate and identify Mycobacterium
      tuberculosis complex more quickly than previously. These developments include
      more rapid detection of growth and tests to identify RNA or DNA of M.
      tuberculosis complex directly in clinical samples. United States Food and Drug
      Administration (FDA) panels have recently recommended approval of two direct
      amplification tests (DAT), the Gen-Probe MTD (San Diego, CA) and the AMPLICOR M.
      tuberculosis test (Roche Diagnostic Systems, Inc., Branchburg, NJ). The FDA has
      approved the MTD for identification of M. tuberculosis complex in respiratory
      specimens that are smear-positive for acid-fast bacilli (AFB). In addition, the
      specimen must be from a patient who has not received antituberculous medication
      for seven or more days or within the last 12 months. From the data reviewed by
      the FDA, the specificity (100%) and sensitivity (95%/96% in the two studies) of
      these two tests in AFB smear-positive specimens were found to be comparable to
      the Accuprobe (Gen-Probe) for identification of M. tuberculosis complex in
      culture, with the advantage that the DAT results are available much sooner. The
      DAT are significantly more sensitive than the AFB smear. However, in AFB smear
      negative samples, the specificity, sensitivity, and positive predictive value
      were 96/99%, 48/53% and 24/58%, respectively, in the two studies. For some
      results, the Gen-Probe assay had the higher value and for others, the Roche assay
      was higher. The DAT result, particularly when discordant with the AFB smear, must
      be used in conjunction with clinical assessment. While both the MTD and the
      AMPLICOR M. tuberculosis test have undergone extensive testing in clinical
      laboratories, neither test has been examined for its utility in routine clinical
      use or public health settings in the United States. An American Thoracic Society
      Workshop was convened to examine the data and technology available to date, to
      develop a consensus addressing the appropriate use of the rapid diagnostic tests
      (in particular, DAT's) for tuberculosis, and to identify future research needs
      and directions. The consensus among three focus groups, clinical, laboratory, and
      public health, was that, while these tests are a major improvement over standard
      techniques, there is currently insufficient information on their clinical and
      public health utility. When the AFB smear and DAT are both positive, the
      diagnosis of tuberculosis can be considered to be established. Furthermore, when
      the AFB smear is negative and the DAT is also negative, it is unlikely that M.
      tuberculosis will be grown from that sample. When there is discordance between
      the AFB smear and the DAT, additional consideration must be given to the overall
      clinical picture and repeat testing should be done. It is recommended that the
      currently available DAT's always be performed in conjunction with microscopy and
      culture, and each test result must be interpreted within the overall clinical
      setting in which it is used.

PMID- 9154897
TI  - Passive respiratory mechanics in healthy infants: the effects of growth, gender
      and smoking.

PMID- 9154898
TI  - Lack of association of induration size with HIV infection among drug users
      reacting to tuberculin.

PMID- 9154899
TI  - Intermittent enteral feeding: the influence on respiratory and digestive tract
      colonization in mechanically ventilated intensive-care-unit patients.

PMID- 9154900
TI  - A closer picture of the K channel gate from ion trapping experiments.

PMID- 9154901
TI  - Keeping it simple: kinetic models for the sodium pump.

PMID- 9154902
TI  - Trapping of organic blockers by closing of voltage-dependent K+ channels:
      evidence for a trap door mechanism of activation gating.
AB  - Small organic molecules, like quaternary ammonium compounds, have long been used
      to probe both the permeation and gating of voltage-dependent K+ channels. For
      most K+ channels, intracellularly applied quaternary ammonium (QA) compounds such
      as tetraethylammonium (TEA) and decyltriethylammonium (C10) behave primarily as
      open channel blockers: they can enter the channel only when it is open, and they
      must dissociate before the channel can close. In some cases, it is possible to
      force the channel to close with a QA blocker still bound, with the result that
      the blocker is "trapped." Armstrong (J. Gen. Physiol. 58:413-437) found that at
      very negative voltages, squid axon K+ channels exhibited a slow phase of recovery
      from QA blockade consistent with such trapping. In our studies on the cloned
      Shaker channel, we find that wild-type channels can trap neither TEA nor C10, but
      channels with a point mutation in S6 can trap either compound very efficiently.
      The trapping occurs with very little change in the energetics of channel gating,
      suggesting that in these channels the gate may function as a trap door or hinged
      lid that occludes access from the intracellular solution to the blocker site and
      to the narrow ion-selective pore.

PMID- 9154903
TI  - Equilibrium of phosphointermediates of sodium and potassium ion transport
      adenosine triphosphatase: action of sodium ion and Hofmeister effect.
AB  - Sodium and potassium ion transport adenosine triphosphatase accepts and donates a
      phosphate group in the course of its reaction sequence. The phosphorylated enzyme
      has two principal reactive states, E1P and E2P. E1P is formed reversibly from ATP
      in the presence of Na+ and is precursor to E2P, which equilibrates with P(i) in
      the presence of K+. We studied equilibrium between these states at 4 degrees C
      and the effect of Na+ on it. To optimize the reaction system we used a Hofmeister
      effect, replacing the usual anion, chloride, with a chaotropic anion, usually
      nitrate. We phosphorylated enzyme from canine kidney with [32P]ATP. We estimated
      interconversion rate constants for the reaction E1P <--> E2P and their ratio. To
      estimate rate constants we terminated phosphorylation and observed decay
      kinetics. We observed E1P or E2P selectively by adding K+ or ADP respectively. K+
      dephosphorylates E2P leaving E1P as observable species; ADP dephosphorylates E1P
      leaving E2P as observable species. We fitted a 2-pool model comprising two
      reactive species or a twin 2-pool model, comprising a pair of independent 2-pool
      models, to the data and obtained interconversion and hydrolysis rate constants
      for each state. Replacing Na+ with Tris+ or lysine+ did not change the ratio of
      interconversion rate constants between E1P and E2P. Thus Na+ binds about equally
      strongly to E1P and E2P. This conclusion is consistent with a model of Pedemonte
      (1988. J. Theor. Biol. 134:165-182.). We found that Na+ affected another
      equilibrium, that of transphosphorylation between ATP x dephosphoenzyme and ADP x
      E1P. We used the reactions and model of Pickart and Jencks (1982. J. Biol. Chem.
      257:5319-5322.) to generate and fit data. Decreasing the concentration of Na+ 10
      fold shifted the equilibrium constant 10-fold favoring ADP x E1P over ATP x
      dephosphoenzyme. Thus Na+ can dissociate from E1P x Na3. Furthermore, we found
      two characteristics of Hofmeister effects on this enzyme.

PMID- 9154904
TI  - The effect of ionic strength and specific anions on substrate binding and
      hydrolytic activities of Na,K-ATPase.
AB  - The physiological ligands for Na,K-ATPase (the Na,K-pump) are ions, and
      electrostatic forces, that could be revealed by their ionic strength dependence,
      are therefore expected to be important for their reaction with the enzyme. We
      found that the affinities for ADP3-, eosine2-, p-nitrophenylphosphate, and V(max)
      for Na,K-ATPase and K+-activated p-nitrophenylphosphatase activity, were all
      decreased by increasing salt concentration and by specific anions. Equilibrium
      binding of ADP was measured at 0-0.5 M of NaCl, Na2SO4, and NaNO3 and in 0.1 M Na
      acetate, NaSCN, and NaClO4. The apparent affinity for ADP decreased up to 30
      times. At equal ionic strength, I, the ranking of the salt effect was NaCl
      approximately Na2SO4 approximately Na-acetate < NaNO3 < NaSCN < NaCl04. We
      treated the influence of NaCl and Na2SO4 on K(diss) for E x ADP as a "pure" ionic
      strength effect. It is quantitatively simulated by a model where the binding site
      and ADP are point charges, and where their activity coefficients are related to I
      by the limiting law of Debye and Huckel. The estimated net charge at the binding
      site of the enzyme was about +1. Eosin binding followed the same model. The NO3-
      effect was compatible with competitive binding of NO3- and ADP in addition to the
      general I-effect. K(diss) for E x NO3 was approximately 32 mM. Analysis of
      V(max)/K(m) for Na,K-ATPase and K+-p-nitrophenylphosphatase activity shows that
      electrostatic forces are important for the binding of p-nitrophenylphosphate but
      not for the catalytic effect of ATP on the low affinity site. The net charge at
      the p-nitrophenylphosphate-binding site was also about +1. The results reported
      here indicate that the reversible interactions between ions and Na,K-ATPase can
      be grouped according to either simple Debye-Huckel behavior or to specific anion
      or cation interactions with the enzyme.

PMID- 9154906
TI  - Molecular analysis of the putative inactivation particle in the inactivation gate
      of brain type IIA Na+ channels.
AB  - Fast Na+ channel inactivation is thought to involve binding of phenylalanine 1489
      in the hydrophobic cluster IFM in L(III-IV) of the rat brain type IIA Na+
      channel. We have analyzed macroscopic and single channel currents from Na+
      channels with mutations within and adjacent to hydrophobic clusters in L(III-IV).
      Substitution of F1489 by a series of amino acids disrupted inactivation to
      different extents. The degree of disruption was closely correlated with the
      hydrophilicity of the amino acid at position 1489. These mutations dramatically
      destabilized the inactivated state and also significantly slowed the entry into
      the inactivated state, consistent with the idea that F1489 forms a hydrophobic
      interaction with a putative receptor during the fast inactivation process.
      Substitution of a phe residue at position 1488 or 1490 in mutants lacking F1489
      did not restore normal inactivation, indicating that precise location of F1489 is
      critical for its function. Mutations of T1491 disrupted inactivation
      substantially, with large effects on the stability of the inactivated state and
      smaller effects on the rate of entry into the inactivated state. Mutations of
      several other hydrophobic residues did not destabilize the inactivated state at
      depolarized potentials, indicating that the effects of mutations at F1489 and
      T1491 are specific. The double mutant YY1497/8QQ slowed macroscopic inactivation
      at all potentials and accelerated recovery from inactivation at negative membrane
      potentials. Some of these mutations in L(III-IV) also affected the latency to
      first opening, indicating coupling between L(III-IV) and channel activation. Our
      results show that the amino acid residues of the IFM hydrophobic cluster and the
      adjacent T1491 are unique in contributing to the stability of the inactivated
      state, consistent with the designation of these residues as components of the
      inactivation particle responsible for fast inactivation of Na+ channels.

PMID- 9154905
TI  - Single-channel kinetics, inactivation, and spatial distribution of inositol
      trisphosphate (IP3) receptors in Xenopus oocyte nucleus.
AB  - Single-channel properties of the Xenopus inositol trisphosphate receptor (IP3R)
      ion channel were examined by patch clamp electrophysiology of the outer nuclear
      membrane of isolated oocyte nuclei. With 140 mM K+ as the charge carrier
      (cytoplasmic [IP3] = 10 microM, free [Ca2+] = 200 nM), the IP3R exhibited four
      and possibly five conductance states. The conductance of the most-frequently
      observed state M was 113 pS around 0 mV and approximately 300 pS at 60 mV. The
      channel was frequently observed with high open probability (mean P(o) = 0.4 at 20
      mV). Dwell time distribution analysis revealed at least two kinetic states of M
      with time constants tau < 5 ms and approximately 20 ms; and at least three closed
      states with tau approximately 1 ms, approximately 10 ms, and >1 s. Higher
      cytoplasmic potential increased the relative frequency and tau of the longest
      closed state. A novel "flicker" kinetic mode was observed, in which the channel
      alternated rapidly between two new conductance states: F1 and F2. The relative
      occupation probability of the flicker states exhibited voltage dependence
      described by a Boltzmann distribution corresponding to 1.33 electron charges
      moving across the entire electric field during F1 to F2 transitions. Channel run
      down or inactivation (tau approximately 30 s) was consistently observed in the
      continuous presence of IP3 and the absence of change in [Ca2+]. Some
      (approximately 10%) channel disappearances could be reversed by an increase in
      voltage before irreversible inactivation. A model for voltage-dependent channel
      gating is proposed in which one mechanism controls channel opening in both the
      normal and flicker modes, whereas a separate independent mechanism generates
      flicker activity and voltage-reversible inactivation. Mapping of functional
      channels indicates that the IP3R tends to aggregate into microscopic (<1 microm)
      as well as macroscopic (approximately 10 microm) clusters. Ca2+-independent
      inactivation of IP3R and channel clustering may contribute to complex [Ca2+]
      signals in cells.

PMID- 9154907
TI  - Molecular analysis of potential hinge residues in the inactivation gate of brain
      type IIA Na+ channels.
AB  - During inactivation of Na+ channels, the intracellular loop connecting domains
      III and IV is thought to fold into the channel protein and occlude the pore
      through interaction of the hydrophobic motif isoleucine-phenylalanine-methionine
      (IFM) with a receptor site. We have searched for amino acid residues flanking the
      IFM motif which may contribute to formation of molecular hinges that allow this
      motion of the inactivation gate. Site-directed mutagenesis of proline and glycine
      residues, which often are components of molecular hinges in proteins, revealed
      that G1484, G1485, P1512, P1514, and P1516 are required for normal fast
      inactivation. Mutations of these residues slow the time course of macroscopic
      inactivation. Single channel analysis of mutations G1484A, G1485A, and P1512A
      showed that the slowing of macroscopic inactivation is produced by increases in
      open duration and latency to first opening. These mutant channels also show a
      higher probability of entering a slow gating mode in which their inactivation is
      further impaired. The effects on gating transitions in the pathway to open Na+
      channels indicate conformational coupling of activation to transitions in the
      inactivation gate. The results are consistent with the hypothesis that these
      glycine and proline residues contribute to hinge regions which allow movement of
      the inactivation gate during the inactivation process of Na+ channels.

PMID- 9154908
TI  - Ca2+-induced Ca2+ release in Chinese hamster ovary (CHO) cells co-expressing
      dihydropyridine and ryanodine receptors.
AB  - Combined patch-clamp and Fura-2 measurements were performed on chinese hamster
      ovary (CHO) cells co-expressing two channel proteins involved in skeletal muscle
      excitation-contraction (E-C) coupling, the ryanodine receptor (RyR)-Ca2+ release
      channel (in the membrane of internal Ca2+ stores) and the dihydropyridine
      receptor (DHPR)-Ca2+ channel (in the plasma membrane). To ensure expression of
      functional L-type Ca+ channels, we expressed alpha2, beta, and gamma DHPR
      subunits and a chimeric DHPR alpha(i) subunit in which the putative cytoplasmic
      loop between repeats II and III is of skeletal origin and the remainder is
      cardiac. There was no clear indication of skeletal-type coupling between the DHPR
      and the RyR; depolarization failed to induce a Ca2+ transient (CaT) in the
      absence of extracellular Ca2+ ([Ca2+]o). However, in the presence of [Ca2+]o,
      depolarization evoked CaTs with a bell-shaped voltage dependence. About 30% of
      the cells tested exhibited two kinetic components: a fast transient increase in
      intracellular Ca2+ concentration ([Ca2+]i) (the first component; reaching 95% of
      its peak <0.6 s after depolarization) followed by a second increase in [Ca2+]i
      which lasted for 5-10 s (the second component). Our results suggest that the
      first component primarily reflected Ca2+ influx through Ca2+ channels, whereas
      the second component resulted from Ca2+ release through the RyR expressed in the
      membrane of internal Ca2+ stores. However, the onset and the rate of Ca2+ release
      appeared to be much slower than in native cardiac myocytes, despite a similar
      activation rate of Ca2+ current. These results suggest that the skeletal muscle
      RyR isoform supports Ca2+-induced Ca2+ release but that the distance between the
      DHPRs and the RyRs is, on average, much larger in the cotransfected CHO cells
      than in cardiac myocytes. We conclude that morphological properties of T-tubules
      and/or proteins other than the DHPR and the RyR are required for functional
      "close coupling" like that observed in skeletal or cardiac muscle. Nevertheless,
      some of our results imply that these two channels are potentially able to
      directly interact with each other.

PMID- 9154909
TI  - Separation of gating properties from permeation and block in mslo large
      conductance Ca-activated K+ channels.
AB  - In this and the following paper we have examined the kinetic and steady-state
      properties of macroscopic mslo Ca-activated K+ currents in order to interpret
      these currents in terms of the gating behavior of the mslo channel. To do so,
      however, it was necessary to first find conditions by which we could separate the
      effects that changes in Ca2+ concentration or membrane voltage have on channel
      permeation from the effects these stimuli have on channel gating. In this study
      we investigate three phenomena which are unrelated to gating but are manifest in
      macroscopic current records: a saturation of single channel current at high
      voltage, a rapid voltage-dependent Ca2+ block, and a slow voltage-dependent Ba2+
      block. Where possible methods are described by which these phenomena can be
      separated from the effects that changes in Ca2+ concentration and membrane
      voltage have on channel gating. Where this is not possible, some assessment of
      the impact these effects have on gating parameters determined from macroscopic
      current measurements is provided. We have also found that without considering the
      effects of Ca2+ and voltage on channel permeation and block, macroscopic current
      measurements suggest that mslo channels do not reach the same maximum open
      probability at all Ca2+ concentrations. Taking into account permeation and
      blocking effects, however, we find that this is not the case. The maximum open
      probability of the mslo channel is the same or very similar over a Ca2+
      concentration range spanning three orders of magnitude indicating that over this
      range the internal Ca2+ concentration does not limit the ability of the channel
      to be activated by voltage.

PMID- 9154911
TI  - Quantitative determination of conformational, dynamic, and kinetic parameters of
      a ligand-protein/DNA complex from a complete relaxation and conformational
      exchange matrix analysis of intermolecular transferred NOESY.
AB  - We report a quantitative analysis of the 13C-edited intermolecular transferred
      NOESY (inter-TrNOESY) spectrum of the trp-repressor/operator complex (trp-rep/op)
      with [ul-13C/15N]-L-tryptophan corepressor using a computer program implementing
      complete relaxation and conformational exchange matrix (CORCEMA) methodology
      [Moseley et al. (1995) J. Magn. Reson. 108B, 243-261]. Using complete mixing time
      curves of three inter-TrNOESY peaks between the tryptophan and the Trp-rep/op,
      this self-consistent analysis determined the correlation time of the bound
      species (tauB = 13.5 ns) and the exchange off-rate (k(off) = 3.6 s(-1)) of the
      corepressor. In addition, the analysis estimated the correlation time of the free
      species (tauF approximately 0.15 ns). Also, we demonstrate the sensitivity of
      these inter-TrNOESY peaks to several factors including the k(off) and orientation
      of the tryptophan corepressor within the binding site. The analysis indicates
      that the crystal structure orientation for the corepressor is compatible with the
      solution NMR data.

PMID- 9154910
TI  - Intrinsic voltage dependence and Ca2+ regulation of mslo large conductance Ca
      activated K+ channels.
AB  - The kinetic and steady-state properties of macroscopic mslo Ca-activated K+
      currents were studied in excised patches from Xenopus oocytes. In response to
      voltage steps, the timecourse of both activation and deactivation, but for a
      brief delay in activation, could be approximated by a single exponential function
      over a wide range of voltages and internal Ca2+ concentrations ([Ca]i).
      Activation rates increased with voltage and with [Ca]i, and approached saturation
      at high [Ca]i. Deactivation rates generally decreased with [Ca]i and voltage, and
      approached saturation at high [Ca]i. Plots of the macroscopic conductance as a
      function of voltage (G-V) and the time constant of activation and deactivation
      shifted leftward along the voltage axis with increasing [Ca]i. G-V relations
      could be approximated by a Boltzmann function with an equivalent gating charge
      which ranged between 1.1 and 1.8 e as [Ca]i varied between 0.84 and 1,000 microM.
      Hill analysis indicates that at least three Ca2+ binding sites can contribute to
      channel activation. Three lines of evidence indicate that there is at least one
      voltage-dependent unimolecular conformational change associated with mslo gating
      that is separate from Ca2+ binding. (a) The position of the mslo G-V relation
      does not vary logarithmically with [Ca]i. (b) The macroscopic rate constant of
      activation approaches saturation at high [Ca]i but remains voltage dependent. (c)
      With strong depolarizations mslo currents can be nearly maximally activated
      without binding Ca2+. These results can be understood in terms of a channel which
      must undergo a central voltage-dependent rate limiting conformational change in
      order to move from closed to open, with rapid Ca2+ binding to both open and
      closed states modulating this central step.

PMID- 9154912
TI  - Phosphorylation of the PCNA binding domain of the large subunit of replication
      factor C by Ca2+/calmodulin-dependent protein kinase II inhibits DNA synthesis.
AB  - Replication factor C (RF-C) is a heteropentameric protein essential for DNA
      replication and DNA repair. It is a molecular matchmaker required for loading of
      the proliferating cell nuclear antigen (PCNA) sliding clamp onto double-strand
      DNA and for PCNA-dependent DNA synthesis by DNA polymerases delta and epsilon.
      The DNA and PCNA binding domains of the large 140 kDa subunit of human RF-C have
      been recently cloned [Fotedar, R., Mossi, R., Fitzgerald, P., Rousselle, T.,
      Maga, G., Brickner, H., Messier, H., Khastilba. S., Hubscher, U., & Fotedar, A.
      (1996) EMBO J. 15, 4423-4433]. Here we show that the PCNA binding domain is
      phosphorylated by the Ca2+/calmodulin-dependent protein kinase II (CaMKII), an
      enzyme required for cell cycle progression in eukaryotic cells. The DNA binding
      domain, on the other hand, is not phosphorylated. Phosphorylation by CaMKII
      reduces the binding of PCNA to RF-C and consequently inhibits RF-C-dependent DNA
      synthesis by DNA polymerases delta1 and epsilon. Once bound to PCNA and DNA, RF-C
      is protected from phosphorylation by CaMKII, suggesting a possible role of CaMKII
      in regulating the dynamics of interaction between PCNA and RF-C and thus
      interfering in the formation of an active sliding clamp by DNA polymerases delta
      and epsilon.

PMID- 9154913
TI  - Combinations of the alpha-helix-turn-alpha-helix motif of TetR with respective
      residues from LacI or 434Cro: DNA recognition, inducer binding, and urea
      dependent denaturation.
AB  - We constructed 10 different variants of TetR by substituting all or some of the
      residues in the alpha-helix-turn-alpha-helix (HTH) operator binding motif with
      the respective amino acids from LacI or 434Cro. The variants were soluble,
      negative transdominant over tetR in vivo, and as active as wild-type TetR in
      tetracycline binding in vitro. The urea-induced denaturation of the 10 variants
      occurs in single reversible transitions, which are centered around 4.3 M urea.
      Denaturation is concentration-dependent, supporting a simple two-state mechanism
      in which the folded dimeric protein is in equilibrium with unfolded monomers. An
      analysis according to the two-state model yields a Gibbs free energy of
      stabilization (at 0 M urea, 25 degrees C) of about 75 kJ/mol, typical for dimeric
      proteins of this size. Even a deletion of 24 residues from the reading head
      decreased the stability by only 2.7 kJ/mol. These results suggest that the DNA
      reading head of Tet repressor is a thermodynamically independent domain and that
      the thermodynamic stability of the Tet repressor dimer is determined by the
      association of the dimerization domains of the individual monomers. Variants
      containing replacements in the first alpha-helix of HTH did not show any DNA
      binding activity whatsoever. We attribute this to the alteration of the two N
      terminal residues in this alpha-helix. TetR variants were active in nonspecific
      DNA binding, when either all or only the solvent-exposed residues in the
      recognition alpha-helix of HTH were exchanged to the respective LacI sequence.
      Replacement of the same residues by the respective amino acids from 434Cro
      yielded hybrid proteins that specifically recognize tetO in vitro. Taken
      together, these results establish that the similarity of operator recognition
      between 434Cro and TetR is greater than between TetR and LacI and confirm that
      prediction of the recognized DNA sequence is not obvious from the sequence of the
      respective HTH or recognition alpha-helix.

PMID- 9154914
TI  - "Designing out" disulfide bonds: thermodynamic properties of 30-51 cystine
      substitution mutants of bovine pancreatic trypsin inhibitor.
AB  - We have used a combination of spectroscopic and calorimetric techniques to assess
      the thermodynamic and extrathermodynamic consequences of paired amino acid
      substitutions at positions 30 and 51 in bovine pancreatic trypsin inhibitor
      (BPTI). Correctly folded, wild type BPTI contains a disulfide at the 30-51
      positions, with the nonbackbone atoms of this cystine being relatively solvent
      inaccessible. Mutants missing this buried 30-51 disulfide adopt a conformation
      very similar to that of the native state of wild type BPTI (Eigenbrot et al.,
      1990, 1992), although they are severely destabilized relative to the wild type
      molecule (Hurle et al., 1990). We have conducted a systematic effort to find the
      energetically most favorable substitution for this buried 30-51 disulfide in
      BPTI. To this end, we have studied and characterized the thermally induced and
      guanidine hydrochloride-induced denaturation transitions for a family of mutants
      in which the amino acid residue(s) at positions 30 and/or 51 have been
      systematically altered. Specifically, we studied the unfolding transitions of the
      following series of residue 30/residue 51 paired substitution mutants: C30A/C51A,
      C30V/C51A, C30G/C51A, C30S/C51A, C30T/C51A, C30A/C51S, C30S/C51S, and C30G/C51M.
      For this series of mutants, comparisons between the relative stabilization free
      energies, derived from analysis of the denaturation profiles, allow us to reach
      the following conclusions: (a) side chains containing polar moieties (Ser and
      Thr) are destabilizing, with this effect being position dependent (i.e., a serine
      substitution is more destabilizing at position 51 than at position 30); (b) the
      destabilizing effects of two serine substitutions are approximately additive,
      suggesting that side chain-side chain hydrogen bonds between the two serine
      hydroxyl groups probably are weak or nonexistent; (c) the thermodynamic impact of
      a Gly30 substitution is consistent with a glycine-induced increase in the
      configurational entropy of the unfolded state; (d) the C30G/C51M mutant is highly
      destabilized relative to the C30A/C51A mutant despite the fact that, based on
      considerations of hydrophobicity and steric fit, substitution of a buried
      disulfide by Gly30 and Met51 would be expected to be optimal. Methionine may be
      particularly ill-suited as a buried disulfide substitute due to the large loss of
      side chain conformational entropy it undergoes during the transition from the
      unfolded to the native state. In the aggregate, our data provide insight into the
      residue-, position-, and context-dependent consequences on protein stability of
      "designing out" the buried 30-51 disulfide bond in the BPTI molecule. These data
      also suggest that a previously unrecognized component of disulfide bridge
      stabilization of proteins is the relatively minor penalty in side chain
      conformational entropy incurred by cystine residues during folding due to their
      severely restricted rotation even in the unfolded state.

PMID- 9154915
TI  - Solution structure of a DNA decamer containing the antiviral drug ganciclovir:
      combined use of NMR, restrained molecular dynamics, and full relaxation matrix
      refinement.
AB  - The nucleoside analog 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (ganciclovir,
      DHPG) is an antiviral drug that is used in the treatment of a variety of herpes
      viruses in immunocompromised patients and in a gene therapy protocol that has
      shown promising activity for the treatment of cancer. To probe the structural
      effects of ganciclovir when incorporated into DNA, we determined and compared the
      solution structure of a modified ganciclovir-containing decamer duplex
      [d(CTG)(ganciclovir)d(ATCCAG)]2 and a control duplex d[(CTGGATCCAG)]2 using
      nuclear magnetic resonance techniques. 1H and 31P resonances in both duplexes
      were assigned using a combination of 2-D 1H and 31P NMR experiments. Proton
      proton distances determined from NOESY data and dihedral angles determined from
      DQF-COSY data were used in restrained molecular dynamics simulations starting
      from canonical A- and B-form DNA models. Both the control and ganciclovir sets of
      simulations converged to B-type structures. These structures were subjected to
      full relaxation matrix refinement to produce final structures that were in
      excellent agreement with the observed NOE intensities. Examination of the final
      ganciclovir-containing structures reveals that the base of the ganciclovir
      residue is hydrogen bonded to its complementary dC and is stacked in the helix;
      in fact, the base of ganciclovir exhibits increased stacking with the 5' base
      relative to the control. Interestingly, some of the most significant distortions
      in the structures occur 3' to the lesion site, including a noticeable kink in the
      sugar-phosphate backbone at this position. Further examination reveals that the
      backbone conformation, sugar pucker, and glycosidic torsion angle of the residue
      3' to the lesion site all indicate an A-type conformation at this position. A
      possible correlation of these structural findings with results obtained from
      earlier biochemical studies will be discussed.

PMID- 9154916
TI  - Characterization of two highly amyloidogenic mutants of transthyretin.
AB  - The plasma protein transthyretin (TTR) has the potential to form amyloid under
      certain conditions. More than 50 different point mutations have been associated
      with amyloid formation that occurs only in adults. It is not known what
      structural changes are introduced into the structure of this otherwise stable
      molecule that results in its aggregation into insoluble amyloid fibrils. On the
      basis of calculations of the frequency of known mutations over the polypeptide,
      we have constructed two mutants in the D-strand of the polypeptide. These
      molecules, containing either a deletion or a substitution at amino acid positions
      53-55, were unstable and spontaneously formed aggregates upon storage in TBS (pH
      7.6). The precipitates were shown to be amyloid by staining with thioflavin T and
      Congo Red. Their ultrastructure was very similar to that of amyloid fibrils
      deposited in the vitreous body of patients with familial amyloidotic
      polyneuropathy type 1 with an amino acid replacement in position 30 (TTRmet30).
      Like amyloid isolated from the vitreous body of the eye, the amyloid precipitates
      generated from the TTR mutants exposed a trypsin cleavage site between amino acid
      residues 48 and 49, while plasma TTRmet30 isolated from amyloidosis patients as
      well as wild-type TTR only showed minor trypsin sensitivity. Our data indicate
      that the mutants we have constructed are similar to amyloid precursors or may
      share structural properties with intermediates on a pathway leading to amyloid
      deposits of plasma TTR.

PMID- 9154917
TI  - Guinea pig and bovine zeta-crystallins have distinct functional characteristics
      highlighting replacements in otherwise similar structures.
AB  - zeta-Crystallin, a major cytosolic protein of guinea pig lens, has been
      characterized as an NADPH:quinone oxidoreductase (EC 1.6.5.5) [Rao et al. (1992)
      J. Biol. Chem. 267, 97-103]. A bovine lens homolog with 83% sequence identity was
      found to have very different functional characteristics. While the bovine lens
      zeta-crystallin exhibits similar physicochemical properties, such as molecular
      weight, hydropathy profile, and predicted secondary structure, and exhibits
      strong immunological cross-reactivity with the guinea pig and human lens zeta
      crystallins, it shows minimal quinone oxidoreductase activity. On the other hand,
      bovine lens zeta-crystallin, but not guinea pig zeta-crystallin, showed a strong
      binding affinity to single-stranded DNA (ssDNA) that could be competed with
      NADPH, the specific cofactor of zeta-crystallin. NADH and dextran sulfate did not
      affect this characteristic of bovine zeta-crystallin and the enzyme showed no
      binding affinity for the heparin-Ultragel A4R. Two-dimensional electrophoresis of
      bovine lens zeta-crystallin showed a distinct pattern of posttranslational charge
      modification as compared to the guinea pig protein. Alignment of eight zeta
      crystallin sequences, and computer modelling of the bovine and human forms based
      on the crystallographically analyzed Escherichia coli form, suggest that if loss
      of a functional residue accounts for the lowered catalytic activity of the bovine
      protein, Tyr 52 of the E. coli enzyme, and the equivalent Tyr present in all
      known mammalian forms except the bovine, is the likely candidate. In the bovine
      form this tyrosine is replaced by histidine.

PMID- 9154918
TI  - Conformational effects of calcium release from parvalbumin: comparison of
      computational simulations with spectroscopic investigations.
AB  - The effect of Ca2+ binding to parvalbumin was monitored by probes of conformation
      including absorption, fluorescence, circular dichroism (CD), infrared (IR)
      spectroscopy and differential scanning calorimetry. These experimental studies
      were compared with molecular dynamics computations on the structures of the Ca
      bound and Ca-free forms of cod parvalbumin. The UV CD spectra show that removal
      of calcium results in a decrease in the alpha-helical content of the protein. The
      IR amide I' and III' regions are very much affected by Ca removal and are
      indicative of significant perturbation of secondary structure. The fluorescence
      of tryptophan, the IR markers, and UV ellipticity all show changes with
      temperature, pointing to a lowering of protein stability upon Ca removal. These
      results are consistent with the structures obtained for both the Ca-bound and Ca
      free proteins after 200 ps of solvated molecular dynamics simulations which show
      a decrease in the secondary structure upon Ca removal.

PMID- 9154919
TI  - Interactions of the vnd/NK-2 homeodomain with DNA by nuclear magnetic resonance
      spectroscopy: basis of binding specificity.
AB  - The interactions responsible for the nucleotide sequence-specific binding of the
      vnd/NK-2 homeodomain of Drosophila melanogaster to its consensus DNA binding site
      have been identified. A three-dimensional structure of the vnd/NK-2 homeodomain
      DNA complex is presented, with emphasis on the structure of regions of observed
      protein-DNA contacts. This structure is based on protein-DNA distance restraints
      derived from NMR data, along with homology modeling, solvated molecular dynamics,
      and results from methylation and ethylation interference experiments. Helix III
      of the homeodomain binds in the major groove of the DNA and the N-terminal arm
      binds in the minor groove, in analogy with other homeodomain-DNA complexes whose
      structures have been reported. The vnd/NK-2 homeodomain recognizes the unusual
      DNA consensus sequence 5'-CAAGTG-3'. The roles in sequence specificity and
      strength of binding of individual amino acid residues that make contact with the
      DNA are described. We show, based primarily on the observed protein-DNA contacts,
      that the interaction of Y54 with the DNA is the major determinant of this
      uncommon nucleotide binding specificity in the vnd/NK-2 homeodomain-DNA complex.

PMID- 9154920
TI  - Crystal structure of an ecotin-collagenase complex suggests a model for
      recognition and cleavage of the collagen triple helix.
AB  - The crystal structure of fiddler crab collagenase complexed with the dimeric
      serine protease inhibitor ecotin at 2.5 A resolution reveals an extended cleft
      providing binding sites for at least 11 contiguous substrate residues. Comparison
      of the positions of nine intermolecular main chain hydrogen bonding interactions
      in the cleft, with the known sequences at the cleavage site of type I collagen,
      suggests that the protease binding loop of ecotin adopts a conformation mimicking
      that of the cleaved strand of collagen. A well-defined groove extending across
      the binding surface of the enzyme readily accommodates the two other polypeptide
      chains of the triple-helical substrate. These observations permit construction of
      a detailed molecular model for collagen recognition and cleavage by this
      invertebrate serine protease. Ecotin undergoes a pronounced internal structural
      rearrangement which permits binding in the observed conformation. The capacity
      for such rearrangement appears to be a key determinant of its ability to inhibit
      a wide range of serine proteases.

PMID- 9154921
TI  - Structural basis for the broad substrate specificity of fiddler crab
      collagenolytic serine protease 1.
AB  - Crab collagenolytic serine protease 1 efficiently cleaves peptide bonds directly
      C-terminal to basic, polar, and hydrophobic amino acids. The crystal structure of
      this enzyme complexed to the protein inhibitor ecotin at 2.5 A resolution reveals
      a large primary binding pocket punctuated on one wall by the side chain of
      aspartate-226. Removal or relocation of this negatively charged group by site
      directed mutagenesis generates variant enzymes which retain very high activities
      toward selected substrates. Full retention of activity toward hydrophobic
      substrates in collagenase D226G is accompanied by a 10-100-fold reduction in
      k(cat)/Km toward basic residues. In contrast, restoration of the negative charge
      in a trypsin-like position in collagenase D226G/G189D regenerates nearly full
      activity toward basic substrates while introducing a 5-fold decrease in k(cat)/Km
      toward hydrophobic amino acids. These results imply that the collagenase S1
      pocket has multiple distinct binding sites for different amino acid side chains,
      a suggestion supported by molecular modeling studies based on the crystal
      structure. The ease of specificity modification in the primary binding site of
      this serine protease parallels similar observations with the bacterial enzymes
      alpha-lytic protease and subtilisin, and stands in sharp distinction to the
      extensive mutagenesis required to alter specificity in trypsin.

PMID- 9154922
TI  - Exceptionally stable salt bridges in cytochrome P450cam have functional roles.
AB  - A long-standing puzzle in structure-function studies of cytochrome P450cam is how
      the substrate, camphor, reaches the buried active site. The crystal structure
      shows no channel from the surface to the active site large enough for substrate
      to pass through. Recent experiments indicate that access of the rather nonpolar
      substrate to the active site is controlled by electrostatic interactions and may
      involve rupture of the two salt links to Asp251 [Deprez, E., Gerber, N. C., Di
      Primo, C., Douzou, P., Sligar, S. G., & Hui Bon Hoa, G. (1994) Biochemistry 33,
      14464-14468]. Consequently, we have computed the electrostatic strength of 53
      ionic pairs, including 32 salt links, in cytochrome P450cam by numerical solution
      of the finite-difference linearized Poisson-Boltzmann equation. The calculated
      electrostatic free energies, delta Gtot, of the salt links range from -9 to +6
      kcal/mol with approximately 60% of the salt links being energetically favorable
      and 40% being unfavorable with respect to mutation to their uncharged, nonpolar
      isosteres. Strikingly, of the four most stable salt links in the protein (delta
      Gtot < -6 kcal/mol), two involve the propionate groups of the heme and the other
      two involve Asp251. In the modeled D251N mutant, for which electrostatic effects
      on substrate binding are diminished, the latter two salt links lose their
      stability (delta Gtot > -2.4 kcal/mol). Thus it appears that cytochrome P450cam
      has evolved four unusually strong salt bridges, stabilized by surrounding charged
      and polar groups in the protein, to keep its heme cofactor in place and to
      regulate substrate binding.

PMID- 9154923
TI  - Effect of nuclear protein HMG1 on in vitro slippage synthesis of the tandem
      repeat dTG x dCA.
AB  - Tandem repeats of simple doublet and triplet sequences occur with high frequency
      in the DNA of eucaryotes. Among the most frequent is the repeat of dTG, which has
      unusual structural properties. We show here that HMG1 (modeled by the second HMG
      box motif from HMG1 of the rat, HMGb) binds to complexes formed from annealing
      unequal lengths of dTG x dCA and inhibits the in vitro elongation of these
      complexes by the Klenow fragment of DNA polymerase I at 37 degrees C. At 46
      degrees C, HMGb enhances the elongation. Polylysine inhibits elongation at both
      temperatures. These results show that the stability of this repeat in vivo can be
      influenced by the presence of basic proteins in general, and more selectively by
      the abundant nuclear protein HMG1.

PMID- 9154924
TI  - Oxidation of ubiquinol by cytochrome bo3 from Escherichia coli: kinetics of
      electron and proton transfer.
AB  - In this study we have used the so-called flow-flash technique to investigate
      electron and proton transfer during the reaction between cytochrome bo3 with
      bound ubiquinol (QH2) and dioxygen. The results are compared to those from the
      well-characterized mitochondrial cytochrome alpha alpha3. Qualitatively, the same
      type of absorbance changes associated with electron transfer were observed in
      both enzymes whereas the protonation reactions were markedly different. In the
      bacterial QH2-bound enzyme, three kinetic phases with time constants of
      approximately 45 micros, approximately 700 micros, and approximately 4 ms
      associated with electron-transfer reactions were observed. The first phase is
      attributed to oxidation of hemes b and o3 and formation of the "peroxy"
      intermediate. The second and third phases were not observed after addition of the
      herbicide HQNO, which displaces QH2 from its binding site. They are attributed to
      electron transfer from QH2 to heme b and from heme b to the binuclear center,
      respectively. In both enzymes, the initial electron transfer was followed by a
      slower uptake of 0.9 +/- 0.3 proton per enzyme molecule (tau approximately 90
      micros), previously attributed to protonation of a group near the binuclear
      center. Only in the bacterial enzyme, the second electron-transfer reaction was
      accompanied by a net release of 1.1 +/- 0.3 H+, which is attributed to proton
      release during oxidation of QH2. It was followed by a slower uptake of 1.2 +/-
      0.4 H+ during transfer of the fourth electron to the binuclear center. The two
      slowest protonation reactions were not observed in the presence of HQNO.

PMID- 9154925
TI  - Serpin conformational change in ovalbumin. Enhanced reactive center loop
      insertion through hinge region mutations.
AB  - Ovalbumin is a noninhibitory member of the serpin superfamily that does not
      spontaneously undergo the loop-to-sheet conformational change upon cleavage of
      its reactive center that is characteristic of inhibitory serpins. We tested the
      hypothesis that ovalbumin could be turned into a proteinase inhibitor by
      increasing the rate of loop insertion through hinge region mutations alone. We
      found that none of the three variants examined showed any detectable proteinase
      inhibitory properties. However, replacement of the P14 arginine residue of
      ovalbumin by serine, either alone or in combination with changes of P12-P10 to
      alanine, resulted in a large increase in the rate of loop insertion into beta
      sheet A following cleavage at the P1-P1' bond by porcine pancreatic elastase
      (PPE), as shown by the spontaneous formation of a loop-inserted form upon
      cleavage that has increased the thermal stability. From the magnitude of the
      increase in stability of the cleaved, loop-inserted forms of the P14 ovalbumin
      variants, as well as the accessibility of the P1-P1'-cleaved reactive center loop
      to further proteolysis at P8-P7, we concluded that the reactive center loop can
      only partially insert into beta-sheet A and therefore that ovalbumin is also
      defective in the ability of beta-sheet A to expand to fully accommodate the whole
      of the reactive center loop. This defect, through its effect on the extent and/or
      rate of loop insertion, is likely to be a principal reason for ovalbumin not
      being a proteinase inhibitor.

PMID- 9154926
TI  - Bovine PAS-6/7 binds alpha v beta 5 integrins and anionic phospholipids through
      two domains.
AB  - Bovine milk fat globule membranes are a rich source of glycoproteins PAS-6 (52
      kDa) and PAS-7 (47 kDa). They are glycosylation variants sharing a common
      polypeptide core. The PAS-6/7 protein consists of two EGF-like domains and a
      tandem repeated structure with a high degree of similarity to the C1 and C2
      domains found in blood-clotting factors V and VIII. The second EGF-like domain
      contains an RGD cell adhesion sequence with the possibility of binding integrins,
      while the C-terminal end of the C2-like domain contains a probable amphipathic
      alpha-helix. Using a PAS-6/7 column, bovine alpha v beta 5 integrin was purified
      from mammary gland tissue by affinity chromatography and characterized by Western
      blotting and N-terminal sequencing. The interaction between PAS-6/7 and the alpha
      v beta 5 integrin was shown to be RGD dependent. Lipid binding assays showed that
      PAS-6/7 binds to surfaces of phosphatidylserine, -inositol, and -glycerol, and
      their precursor, phosphatidic acid, but not phosphatidylcholine. Furthermore, PAS
      6/7 displayed the highest affinity toward a total lipid fraction derived from the
      milk fat globule membrane as compared to pure phospholipids. Using Western
      blotting technique, PAS-6/7 was shown to be widely expressed in a number of
      tissues. These results show that PAS-6/7 is a common protein which can bind to
      membranes by two distinct mechanisms, one through affinity to integrin alpha v
      beta 5 and another by direct binding to phospholipids.

PMID- 9154927
TI  - A stereoselective cobalt-containing nitrile hydratase.
AB  - Nitrile hydratase from Pseudomonas putida NRRL-18668 has been purified and
      characterized. The purified enzyme catalyzes the hydration of 2(S)-(4'
      chlorophenyl)-3-methylbutyronitrile at least fifty times faster than that of 2(R)
      (4'-chlorophenyl)-3-methylbutyronitrile. This enzyme is a member of the class of
      nitrile hydratase that contains cobalt. Visible absorption and CD spectra suggest
      the cobalt exists as a non-corrin low-spin Co3+ ion in a tetragonally-distorted
      octahedral ligand field. Chemical reduction of the native enzyme results in a
      species with the EPR signature of a low-spin Co2+ complex. Like the other cobalt
      containing nitrile hydratases, this enzyme is relatively stable, maintaining its
      activity below 35 degrees C, and it shows a broad activity optimum between pH 7.2
      and 7.8. The structural genes for this enzyme have been cloned and sequenced. The
      deduced amino acid sequences for the alpha and beta subunits show 48-63% and 35
      41% homology, respectively, to other sequenced nitrile hydratases. In particular,
      the cysteine residues in the alpha subunit that have been suggested to coordinate
      the metal ion in the iron-containing nitrile hydratases [Brennan, B. A.,
      Cummings, J. G., Chase, D. B., Turner, I. M., Jr., & Nelson, M. J. (1996)
      Biochemistry 35, 10068-10077] are conserved in this enzyme, suggesting that this
      nitrile hydratase, like the enzyme from Rhodococcus rhodochrous J1, is a member
      of a newly described class of metalloenzymes with Co3+-thiolate ligation
      [Brennan, B. A., Alms, G., Nelson, M. J., Durney, L. T., & Scarrow, R. C. (1996)
      J. Am. Chem. Soc. 118, 9194-9195].

PMID- 9154928
TI  - Effects of serpin binding on the target proteinase: global stabilization,
      localized increased structural flexibility, and conserved hydrogen bonding at the
      active site.
AB  - The binding of human alpha1-proteinase inhibitor to rat trypsin was shown by NMR
      spectroscopy to raise the pKa' of His57 in the active site but not to disrupt the
      hydrogen bond between His57 and Asp102. Similar NMR results were observed for the
      Asp189 to serine mutant of rat trypsin, which is much more stable than wild-type
      trypsin against autoproteolysis as the result of mutation of the residue at the
      base of the specificity pocket. This mutant was used in further studies aimed at
      determining the extent of the conformational transition in trypsin that
      accompanies serpin binding and leads to disruption of the catalytic activity of
      the proteinase such that the inhibitor complex is trapped at the acyl enzyme
      intermediate stage. The stability of rat trypsin toward thermal denaturation was
      found to be lower in the free enzyme than in the complex with alpha1-proteinase
      inhibitor. This suggests that the complex contains extensive protein-protein
      interactions that stabilize overall folding. On the other hand, previous
      investigations have shown that the proteinase in serpin-proteinase complexes
      becomes more susceptible to limited proteolysis, suggesting that the
      conformational change that accompanies binding leads to the exposure of
      susceptible loops in the enzyme. The existence of this type of conformational
      change upon complex formation has been confirmed here by investigation of the
      rate of cleavage of disulfide linkages by added dithiothreitol. This study
      revealed that, despite the increased stability of trypsin in the complex, one or
      more of its disulfide bridges becomes much more easily reduced. We suggest that
      the process of complex formation with alpha1-proteinase inhibitor converts
      trypsin D189S into an inactive, loose structure, which serves as a
      "conformational trap" of the enzyme that prevents catalytic deacylation. It is
      also proposed that plastic region(s) of the activation domain of trypsin may play
      a crucial role in this inhibitor-induced structural rearrangement.

PMID- 9154929
TI  - Structural domains that contribute to substrate specificity in facilitated
      glucose transporters are distinct from those involved in kinetic function:
      studies with GLUT-1/GLUT-2 chimeras.
AB  - GLUT-2 differs from other members of the facilitated glucose transporter family
      because it transports a wider range of substrates and exhibits a higher Km for
      transport of glucose analogs such as 2-deoxyglucose (2-DOG). In order to
      investigate the structural determinants of the unique substrate specificity and
      kinetic function of GLUT-2, recombinant adenoviruses were used to express native,
      mutant, and chimeric glucose transporters in the kidney cell line CV-1, yielding
      the following key observations. (1) A chimera consisting of GLUT-1 with the C
      terminal tail of GLUT-2 had a Km for 2-DOG of 9.9 +/- 1.5 that was intermediate
      between that of native GLUT-1 (3.7 +/- 0.4) and native GLUT-2 (26.3 +/- 3.3). In
      contrast to the effect of the GLUT-2 C terminus on Km for 2-DOG, this
      substitution did not confer enhanced uptake of three alternative substrates
      (fructose, arabinose, or streptozotocin) which are transported efficiently by
      native GLUT-2 but not by GLUT-1. (2) A chimera consisting of GLUT-2 with the N
      terminal 87 amino acids of GLUT-1 exhibited no change in Km for 2-DOG relative to
      native GLUT-2 but exhibited a significant reduction in capacity for transport of
      the three alternative substrates. (3) Mutation of asparagine 62 in GLUT-2 to
      glutamine produced a transporter lacking its N-linked oligosaccharide that
      exhibited a 2.5-fold increase in Km for 2-DOG but equally efficient transport of
      the three alternative substrates relative to native GLUT-2. These data provide
      insight into structural domains that affect substrate specificity in facilitated
      glucose transporters and demonstrate that they are distinct from elements
      involved in glucose transport kinetics.

PMID- 9154930
TI  - Anionic phospholipids modulate peptide insertion into membranes.
AB  - While the insertion of a hydrophobic peptide or membrane protein segment into the
      bilayer can be spontaneous and driven mainly by the hydrophobic effect, anionic
      lipids, which comprise ca. 20% of biological membranes, provide a source of
      electrostatic attractions for binding of proteins/peptides into membranes. To
      unravel the interplay of hydrophobicity and electrostatics in the binding of
      peptides into membranes, we designed peptides de novo which possess the typical
      sequence Lys-Lys-Ala-Ala-Ala-X-Ala-Ala-Ala-Ala-Ala-X-Ala-Ala-Trp-Ala-Ala-X-Ala-Al
      a-Ala-Lys-Lys-Lys-Lys-amide, where X residues correspond to "guest" residues
      which encompass a range of hydrophobicity (Leu, Ile, Gly, and Ser). Circular
      dichroism spectra demonstrated that peptides were partially (40-90%) random in
      aqueous buffer but were promoted to form 100% alpha-helical structures by anionic
      lipid micelles. In neutral lipid micelles, only the relatively hydrophobic
      peptides (X = L and I) spontaneously adopted the alpha-helical conformation, but
      when 25% of negatively charged lipids were mixed in to mimic the content of
      anionic lipids in biomembranes, the less hydrophobic (X = S and G) peptides then
      formed alpha-helical conformations. Consistent with these findings, fluorescence
      quenching by the aqueous-phase quencher iodide indicated that in anionic
      (dimyristoylphosphatidylglycerol) vesicles, the peptide Trp residue was buried in
      the lipid vesicle hydrophobic core, while in neutral
      (dimyristoylphosphatidylcholine) vesicles, only hydrophobic (X = L and I)
      peptides were shielded from the aqueous solution. Trp emission spectra of
      peptides in the presence of phospholipids doxyl-labeled at the 5-, 7-, 10-, 12-,
      and 16-fatty acid positions implied not only a transbilayer orientation for
      inserted peptides but also that mixed peptide populations (transbilayer + surface
      associated) may arise. Overall results suggest that for hydrophobic peptides with
      segmental threshold hydrophobicity below that which promotes spontaneous membrane
      insertion, primary electrostatic attractions provided by anionic phospholipids
      become essential for peptide binding and insertion to membranes.

PMID- 9154931
TI  - The inhibitory complex of smooth muscle caldesmon with actin and tropomyosin
      involves three interacting segments of the C-terminal domain 4.
AB  - We have designed a series of recombinant peptides derived from the C-terminus of
      human caldesmon (amino acids 663-793, domain 4) to determine the structural basis
      of the multiple-sited caldesmon-actin-tropomyosin interaction. All the
      recombinant peptides are able to bind to actin and inhibit actin-activated myosin
      ATPase activity; 1 mol of peptide is bound per actin for >90% inhibition.
      However, equivalent inhibition of actin-tropomyosin activation of myosin ATPase
      requires less than one peptide per seven actin to be bound. We have found two
      sequences, H2 (amino acids 683-767) and H2+12 (amino acids 683-779), from the
      center of domain 4 which potentiate actin-tropomyosin filament activity; i.e.,
      their effect is opposite to caldesmon. Maximum potentiation correlates with one
      H2 or H2+12 bound per four actin. This effect is completely dependent upon the
      presence of tropomyosin on the actin filament. H2 and H2+12 also increase actin
      tropomyosin filament velocity in the in vitro motility assay. If the H2 sequence
      is extended by 20 amino acids at the N-terminal end to the N-terminus of domain
      4, the peptide becomes an inhibitor. If H2 is extended by 19 amino acids at its C
      terminus, it becomes a tropomyosin-dependent inhibitor, and with a further
      extension of 7 amino acids to reach the C-terminus of human caldesmon (H2+26),
      inhibition is more potent. We conclude that three regions in domain 4 of
      caldesmon contribute to tropomyosin-dependent inhibition of actomyosin ATPase: a
      central segment [747-767 (690-710 in the chicken sequence)], which is essential
      but not sufficient for tropomyosin-dependent inhibition of actomyosin ATPase; and
      two actin binding segments N-terminal and C-terminal to this segment, 663-682
      (606-625) and 770-793 (713-737). If only the central segment is present (H2,
      H2+12), the actin-tropomyosin-caldesmon peptide complex is not inhibitory, and
      its properties resemble actin-tropomyosin-caldesmon-Ca2+ x calmodulin.

PMID- 9154932
TI  - Trp86 --> Phe replacement in bacteriorhodopsin affects a water molecule near
      Asp85 and light adaptation.
AB  - Illumination of the Trp86 --> Phe mutant of bacteriorhodopsin causes anomalous
      light adaptation, i.e., isomerization of the retinal from all-trans to 13-cis, 15
      syn. FTIR spectral analysis shows that illumination at 250 K yields two 13-cis
      photoproducts, the conventional 13-cis, 15-syn state, BR(C), and another termed
      BR(X). BR(X) is different from BR(C) because it has a lower N-H in-plane bending
      frequency and a higher C14-C15 stretching frequency, as well as an absence of
      coupling between these modes. BR(X), which is stable at 275 K, is more abundant
      in the photosteady state produced by longer wavelength light and detected as the
      only photoproduct at 170 K. Its different structural features result from
      distortion of the C14-C15 bond of the chromophore. In the W86F mutant protein,
      the small structural changes of a water molecule in the conversion between the
      all-trans and 13-cis, 15-syn forms and in the formation of the K
      photointermediate are absent, but the larger changes of water molecule(s) that
      normally occur in the L and M intermediates are present. We propose that Trp86,
      together with Asp85, is involved in binding the water molecule and in preventing
      the formation of the 13-cis, 15-syn photoproducts, BR(C) and BR(X), when the wild
      type protein is illuminated.

PMID- 9154933
TI  - Influence of conserved amino acids on the structure and environment of the heme
      of cytochrome c2. A resonance Raman study.
AB  - Resonance Raman spectra using Soret excitations of oxidized and reduced
      Rhodobacter capsulatus cytochrome c2 at pH 7.5 were studied. The spectra of
      oxidized cytochrome c2 show three components for the v10 mode at 1638, 1633, and
      1629 cm(-1). The intensities of these components are sensitive to the excitation
      wavelength. This effect is explained in the context of a conformational
      equilibrium of the ferriheme between a nearly planar structure and two ruffled
      structures. In the case of reduced cytochrome c2, the absolute frequencies as
      well as the excitation-dependent frequency dispersion of the v10 mode (1618-1621
      cm(-1)) indicate a displacement of the conformational equilibrium of heme toward
      the more planar structures. To measure the influence of some key amino acid
      residues on the heme-protein interaction of cytochrome c2, four site-directed
      mutants of Rb. capsulatus cytochrome c2 have been studied by resonance Raman
      spectroscopy and their spectra compared with the spectra obtained for the wild
      type cytochrome. The mutants studied are K14E/K32E, P35A, W67Y, and Y75F. The
      spectral changes induced by the mutations are interpreted in terms of alterations
      in the structure and/or environment of the cytochrome c2 heme in the framework of
      the expected role of the different amino acid residues in the stability and redox
      potential.

PMID- 9154934
TI  - Membrane localization, topology, and mutual stabilization of the rnfABC gene
      products in Rhodobacter capsulatus and implications for a new family of energy
      coupling NADH oxidoreductases.
AB  - The rnf genes in Rhodobacter capsulatus are unique nitrogen fixation genes that
      encode potential membrane proteins (RnfA, RnfD, and RnfE) and potential iron
      sulfur proteins (RnfB and RnfC). In this study, we first analyzed the
      localization and topology of the RnfA, RnfB, and RnfC proteins. By activity and
      immunoblot analysis of expression of translational fusions to Escherichia coli
      alkaline phosphatase, RnfA protein was shown to span the chromatophore membrane
      with its odd-numbered hydrophilic regions exposed to periplasm. By alkaline
      treatment of membrane fractions and following immunoblot analysis using
      antibodies against recombinant proteins expressed in E. coli, both RnfB and RnfC
      proteins were revealed to situate at the periphery of the chromatophore
      membranes. Second, mutual interaction of the Rnf proteins was analyzed by
      immunochemical determinations of RnfB and RnfC proteins in rnf mutants and their
      complemented derivatives. The contents in cellular fractions indicated that RnfB
      and RnfC stabilize each other and that the presence of RnfA is necessary for
      stable existence of both proteins. These results support a hypothesis that the
      Rnf products are subunits of a membrane complex. Finally, we detected homologs of
      rnf genes in Haemophilus influenzae and Vibrio alginolyticus by data base
      searches and in E. coli by cloning of a fragment of an rnfA homolog followed by a
      data base search. Close comparisons revealed that RnfC has potential binding
      sites for NADH and FMN which are similar to those found in proton-translocating
      NADH:quinone oxidoreductases and that RnfA, RnfD, and RnfE show similarity to
      subunits of sodium-translocating NADH:quinone oxidoreductases. We predict that
      the putative Rnf complex represents a novel family of energy-coupling NADH
      oxidoreductases.

PMID- 9154935
TI  - Effects of mutations of aspartic acid 63 on the metal-binding properties of the
      recombinant N-lobe of human serum transferrin.
AB  - Mutations of the aspartic acid residue at position 63 of the N-lobe of human
      serum transferrin substantially alter the metal ion- and anion-binding properties
      of the protein. Substitution of serine, asparagine, glutamic acid, or alanine
      results in the loss of a key component of the interface in the interdomain cleft
      and the metal-binding ligand, aspartic acid, leading in all cases to an increased
      preference for NTA rather than carbonate as the "synergistic" anion relative to
      the wild-type protein. Excess bicarbonate is required to eliminate the NTA and
      obtain the "correct" visible spectrum. Carbonate replaces NTA via an
      intermediate. Blue shifts for the characteristic absorption band of each mutant
      show a range of effects on the Fe-O (Tyr) interaction. Titration with Co(III)
      yielded the molecular absorption coefficient for each mutant except D63A, where
      Co(III) appeared to oxidize the tyrosine residues and damage the ability of the
      mutant to bind metal. The chelator, Tiron, removes iron from hTF/2N with a simple
      saturation kinetic mode with respect to the ligand concentration. Chloride
      inhibits the release in an interesting manner: the effect is initially sharp and
      then levels off with a minimum k(obs) at [KCl] = 0.5 M. However, the reaction of
      the D63 mutants with Tiron results in the formation of the ternary complexes Fe
      hTF/2N-Tiron. Significant red shifts for the characteristic absorption bands of
      these complexes suggest a different ligation of Tiron in the mutants from that in
      wild-type hTF/2N.

PMID- 9154937
TI  - Cryoenzymic studies on yeast 3-phosphoglycerate kinase. Attempt to obtain the
      kinetics of the hinge-bending motion.
AB  - This is a continuation of a study on the 3-phosphoglycerate kinase (PGK) reaction
      in the direction of 1,3-bisphosphoglycerate (bPG) formation: ATP + 3
      phosphoglycerate (PG) <==> ADP + bPG [Schmidt, P. P., Travers, F., & Barman, T.
      (1995) Biochemistry 34, 824-832]. We showed that species containing bPG
      accumulate in the steady state, but their low concentrations and rapid kinetics
      of formation precluded a full study, even under cryoenzymic conditions in 40%
      ethylene glycol. Here we studied the PGK reaction in 30% methanol. The transient
      kinetics of bPG formation were obtained by chemical sampling: PGK was mixed with
      PG and [gamma-32P]ATP in a rapid flow quench apparatus, the mixture aged 4 ms up
      and quenched in acid, and the [1-(32)P]bPG was determined. The time course
      consisted of a rapid rise of bPG (kinetics k(obs)) and a steady state phase. In
      methanol, the amplitude of the rise was large (>50% of the PGK in the steady
      state), and k(obs) was measurable. Fluorescence stopped flow was used to study
      the formation of the binary E x PG and E x ATP. The affinities of PGK for ATP and
      PG were high in methanol (Kd = 102 and 1.5 microM, respectively), but the
      kinetics of the formation of E x PG and E x ATP were too rapid to be measured.
      From these and the chemical sampling experiments, we propose a reaction scheme
      for PGK: a rapid formation of the collision complex E x PG x ATP (K1), a slow
      isomerisation to E* x PG x ATP (k2,k(-2)), a rapid phosphorylation transfer step
      to E x bPG x ADP (K3), and a slow release of the products (k4). In our scheme,
      k(obs) is the reflection mainly of k2 and k(-2) and the steady state of k4. Using
      a computer simulation procedure, k2/K1 = 0.37 microM(-1) s(-1), k(-2) = 33 s(-1),
      K3 = 4, and k4 = 7.1 s(-1). We propose that k(obs) measures the kinetics of the
      putative hinge-bending motion of PGK, i.e., the conformational change that is
      necessary for the substrates to line up for phosphoryl transfer.

PMID- 9154936
TI  - Purified leukocyte cytochrome b558 incorporated into liposomes catalyzes a
      cytosolic factor dependent diaphorase activity.
AB  - The leukocyte iodonitrotetrazolium violet (INT) reductase activity of disrupted
      bovine polymorphonuclear neutrophils is closely associated with the activation of
      the O2(-)-generating NADPH oxidase in a cell-free system. It is dependent upon
      NADPH, cytosolic factors, and amphiphiles (such as arachidonate), the same
      factors required for O2- generation. Both O2- generation and INT reductase
      activity are inhibited by phenylarsine oxide, an inhibitor of the activation of
      the NADPH oxidase [Li, J., & Guillory, R. J. (1997) J. Biochem. Mol. Biol.
      Biophys. (in press)]. In this report, the INT diaphorase activity of disrupted
      bovine polymorphonuclear neutrophils is shown to be resolved by DEAE-Sepharose
      chromatography into two fractions: an NADPH-cytochrome c reductase-containing
      fraction and a cytochrome b558-associated fraction. The diaphorase activity in
      the NADPH-cytochrome c reductase-containing portion is not dependent upon the
      presence of an amphiphile or phospholipid and is not associated with O2-
      generation. Upon incorporation into liposomes, the cytochrome b558-containing
      fraction demonstrates high O2- and INT reductase activities in the presence of
      cytosolic factors. Both O2- generation and INT reductase activities are SDS and
      FAD dependent and further stimulated by GTPgammaS. Phenylarsine oxide inhibits
      both O2- generation and INT reductase activities when added prior to activation
      by SDS. With the cytochrome b-containing liposomes, the Km values (O2- formation)
      for NADPH and NADH are 27.2 microM and 810 microM, and for INT reductase the Km
      values are 27.5 microM and 1017 microM, respectively. Under anaerobic conditions
      and thus in the absence of O2- formation, the NADPH-dependent INT reductase
      activity does not change, indicating that the dye reduction is not due to its
      direct reduction by O2 anion but is an intrinsic property of the superoxide
      generating NADPH oxidase. Cytochrome b558 is the essential component of the NADPH
      oxidase and contains all the redox centers necessary for electron flow between
      NADPH and oxygen. The correlation of the activation and inhibition patterns for
      O2- generation and INT reduction by cytochrome b558 incorporated into artificial
      liposomes strongly indicates that the two activities are associated with the same
      membrane protein, cytochrome b558.

PMID- 9154939
TI  - Cytochrome c folding kinetics studied by time-resolved electrospray ionization
      mass spectrometry.
AB  - A new method for studying the folding kinetics of proteins is described. The
      method combines a continuous flow mixing technique with an electrospray mass
      spectrometer. Different protein conformations in solution are detected by the
      different charge states they produce during electrospray ionization. Unfolded
      proteins generally have more accessible protonation sites and give higher charge
      states than native proteins. The method is applied to study the refolding of acid
      denatured cytochrome c. Global data analysis is used to obtain the exponential
      lifetimes which are associated with the refolding process. The kinetics can be
      described by two lifetimes of 0.17 +/- 0.02 and 8.1 +/- 0.9 s which are in
      accordance with the results of stopped flow experiments previously described in
      the literature. These lifetimes are associated with roughly 90 and 10% of the
      total intensity changes in the mass spectrum, respectively, and most likely
      reflect fast and slow refolding subpopulations of cytochrome c in solution.

PMID- 9154938
TI  - Acyl-CoA binding proteins inhibit the nonenzymic S-acylation of cysteinyl
      containing peptide sequences by long-chain acyl-CoAs.
AB  - Acyl-CoA binding proteins (ACBPs) from rat and bovine liver were found to inhibit
      the nonenzymic S-acylation of two representative types of peptides by long-chain
      acyl-CoAs. As demonstrated previously [Quesnel, S. & Silvius, J. R. (1994)
      Biochemistry 33 13340-13348; Bharadwaj, M., & Bizzozero, O. A. (1995) J.
      Neurochem. 65, 1805-1815], peptides with the sequences myristoyl-GCG, myristoyl
      GCV, and IRYCWLRR-NH2, all representing physiological S-acylation sites in
      mammalian proteins, become S-acylated at appreciable rates in the presence of
      long-chain acyl-CoAs and large unilamellar lipid vesicles. Addition of ACBP at
      physiological molar ratios with respect to long-chain acyl-CoAs strongly inhibits
      the spontaneous S-acylation reaction, in a manner that can be quantitatively
      described by assuming that the ACBP sequesters the acyl-CoA with nanomolar
      affinity in a complex unable to serve as an S-acyl donor. From these results, we
      calculate that at physiological (intracellular) concentrations of ACBP, long
      chain acyl-CoAs, and membrane lipids the expected half-times for spontaneous S
      acylation of such protein sequences by long-chain acyl-CoAs will lie in the range
      of several tens of hours. The nonenzymic reaction of protein cysteine residues
      with long-chain acyl-CoAs is thus unlikely to contribute significantly to the
      physiological modification of signaling and other proteins that show relatively
      rapid rates of S-acylation in mammalian cells. However, it cannot be excluded
      that a nonenzymic reaction with long-chain acyl-CoAs could contribute to the
      physiological S-acylation of certain membrane proteins if the latter exhibit very
      slow kinetics of S-acylation in vivo.

PMID- 9154940
TI  - Nonsequential unfolding of the alpha/beta barrel protein indole-3-glycerol
      phosphate synthase.
AB  - The folding of the enzyme indole-3-glycerol-phosphate synthase (IGPS), a member
      of the (alpha/beta)8 fold family, has been studied. At least two folding
      intermediates have been detected using spectroscopic and activity measurements in
      combination with gel filtration chromatography. These two intermediates are
      produced by parallel pathways of a nonsequential unfolding mechanism rather than
      being consecutive steps in a sequential process. One intermediate can be detected
      in unfolding experiments because it is kinetically trapped in that conformation,
      but it is not observed in refolding experiments. It has spectroscopic and
      hydrodynamic properties very similar to those of the native protein, but it is
      inactive. The other intermediate could not be characterized because it either
      aggregates or unfolds under our experimental conditions and could not be isolated
      chromatographically.

PMID- 9154941
TI  - Multiple interactions between polyphenols and a salivary proline-rich protein
      repeat result in complexation and precipitation.
AB  - Polyphenols (tannins) in the diet not only precipitate oral proteins, producing
      an astringent sensation, but also interact with dietary proteins and digestive
      enzymes in the gut, resulting in a variety of antinutritive and toxic effects.
      Salivary proline-rich proteins (PRPs), which are secreted into the oral cavity,
      form complexes with and precipitate dietary polyphenols, and thus, they
      constitute the primary mammalian defense directed against ingested tannins. In
      order to characterize the interaction, NMR studies were performed which involved
      titrating a series of polyphenols into a synthetic 19-residue PRP fragment. The
      results show that the predominant mode of association is a hydrophobic stacking
      of the polyphenol ring against the pro-S face of proline and that the first
      proline residue of a Pro-Pro sequence is a particularly favored binding site.
      Measurement of dissociation constants indicates that the larger and more complex
      polyphenols interact more strongly with the PRP fragment; the order of binding
      affinity was determined as procyanidin dimer B-2 > pentagalloylglucose >
      trigalloylglucose >> proanthocyanidin monomer (-)-epicatechin approximately
      propyl gallate. Smaller polyphenols can bind with one phenolic ring stacked
      against each proline residue, whereas larger polyphenols occupy two or three
      consecutive prolines. The more complex polyphenols interact with the PRP fragment
      in a multidentate fashion; moreover, they self-associate or stack when bound.
      Thus, a model is proposed in which multiple polyphenol/polyphenol and
      polyphenol/PRP interactions act cooperatively to achieve precipitation.

PMID- 9154942
TI  - Crystal structures of ribonuclease A complexes with 5'-diphosphoadenosine 3'
      phosphate and 5'-diphosphoadenosine 2'-phosphate at 1.7 A resolution.
AB  - High-resolution (1.7 A) crystal structures have been determined for bovine
      pancreatic ribonuclease A (RNase A) complexed with 5'-diphosphoadenosine 3'
      phosphate (ppA-3'-p) and 5'-diphosphoadenosine 2'-phosphate (ppA-2'-p), as well
      as for a native structure refined to 2.0 A. These nucleotide phosphates are the
      two most potent inhibitors of RNase A reported so far, with Ki values of 240 and
      520 nM, respectively. The binding modes and conformations of ppA-3'-p and ppA-2'
      p were found to differ markedly from those anticipated on the basis of earlier
      structures of RNase A complexes. The key difference is that the 5'-beta-phosphate
      rather than the 5'-alpha-phosphate of each inhibitor occupies the P1 phosphate
      binding site. As a consequence, the ribose moieties of the two nucleotides are
      shifted by approximately 2 A compared to the positions of their counterparts in
      earlier complexes, and the adenine rings are rotated into unusual syn
      conformations. Thus, the six-membered and five-membered rings of both adenines
      are reversed with respect to the others but nonetheless engage in extensive
      interactions with the residues that form the B2 purine binding site of RNase A.
      Despite the close structural similarity of the two inhibitors, the puckers of
      their furanose rings are different: C2'-endo and C3'-endo, respectively.
      Moreover, their 5'-alpha-phosphates and 3'(2')-monophosphates interact with
      largely different sets of RNase residues. The results of this crystallographic
      study emphasize the difficulties inherent in qualitative modeling of protein
      inhibitor interactions and the compelling reasons for high-resolution structural
      studies in which quantitative design of improved inhibitors was enabled. The
      structures presented here provide a promising starting point for the rational
      design of tight-binding RNase inhibitors, which may be used as therapeutic agents
      in restraining the ribonucleolytic activities of RNase homologues such as
      angiogenin, eosinophil-derived neurotoxin, and eosinophil cationic protein.

PMID- 9154943
TI  - Toward an efficient DNAzyme.
AB  - A 33-nucleotide, guanine-rich DNA oligomer, PS5.ST1, has been reported to
      catalyze the metallation of mesoporphyrin IX (MPIX) by copper and zinc ions. In
      this paper we report a thorough investigation of the properties of this DNAzyme.
      We have established that a 24-nucleotide sequence (PS5.M), from within PS5.ST1,
      is both the minimal and most optimal catalytic unit. We have found that three
      related porphyrins are acceptable as substrates by this DNAzyme, of which
      protoporphyrin IX is preferred as a substrate over the expected substrate, MPIX.
      We have determined that it is unlikely that a strong, catalytically relevant
      binding site for copper ions exists in the DNAzyme and that high concentrations
      of copper destroy the active DNAzyme. This enzyme, whose folded structure likely
      contains guanine quartets, requires potassium ions for activity; we have shown
      that as little as 1 mM potassium is sufficient for its catalytic robustness,
      whereas as much as 0.5 M sodium still will not support catalysis. In determining
      the pH, temperature, and salt optima for the catalyzed reaction, we have found an
      unexpected stabilizing role for Tris buffer in both the catalyzed and background
      metallation reactions. As a consequence of various steps of optimization, we now
      have a vastly improved DNAzyme, one whose enzymatic parameters compare well both
      with those of natural ferrochelatases, as well as with those of artificially
      derived chelatases, composed of protein (a catalytic antibody) and RNA. The
      existence of this array of biocatalysts for porphyrin metallations allows one-to
      one comparisons of the ways in which different biopolymers solve a given
      catalytic problem.

PMID- 9154944
TI  - Colchicine binding to tubulin monomers: a mechanistic study.
AB  - The kinetic and thermodynamic parameters for colchicine-tubulin and
      deacetamidocolchicine-tubulin interaction, under the condition where tubulin is
      predominantly in its dissociated state (approximately 80% monomer), have been
      determined. We observe that the kinetic parameters exihibit marked change when
      colchicine interacts with the monomeric form of tubulin rather than with the
      dimeric form of tubulin. The reaction of colchicine with tubulin monomers is
      characterized by an enhanced association rate which is a consequence of the
      lowering of activation energy. Colchicine-tubulin interaction, which is only
      poorly reversible, becomes partially reversible under this condition. Differences
      were also noticed in the thermodynamic parameters: the reaction of colchicine
      with tubulin monomers is enthalpy driven with small positive entropy, while with
      tubulin dimers a large positive entropy change was reported. However, no such
      changes in the binding parameters were observed for the reaction involving
      deacetamidocolchicine (a colchicine analog devoid of a side chain at the C-7
      position of B-ring) with tubulin monomers. We therefore conclude that a single
      subunit of tubulin is capable of binding colchicine and that the unusual
      properties of colchicine-tubulin interactions such as the slow association rate,
      high activation energy, and the poor reversibility are due to the possible
      contact(s) of the C-7 substituent (in the B-ring) of colchicine with the other
      subunit of tubulin.

PMID- 9154945
TI  - Steroid pretreatment improves graft recovery in a sheep orthotopic heart
      transplantation model.
AB  - BACKGROUND: Previous reports provide conflicting evidence concerning effects of
      steroids on recovery of cardiac function during procedures involving
      cardiopulmonary bypass. This study was designed to test the hypothesis that
      pretreatment of animals with steroids before heart transplantation improves graft
      hemodynamic function. METHODS: Four groups of sheep were studied: CON, nonsteroid
      treated nontransplanted controls (n = 8); CON-S, steroid-treated nontransplanted
      controls (n = 5); TX, nonsteroid-treated transplanted animals (n = 5); and TX-S,
      steroid-treated transplanted animals (n = 5). Steroid-treated animals were given
      methylprednisolone 30 mg/kg immediately before surgery. Procedures for harvest
      and orthotopic transplantation were similar to those used clinically. Contractile
      function, left ventricular diameter, and cardiac output of control and
      transplanted hearts were measured for 6 hours. A 2 x 2 factorial repeated
      measures analysis of variance was used to determine statistical significance (p <
      0.05). RESULTS: Steroid pretreatment produced significantly higher function in
      controls and transplanted animals compared with nonsteroid-treated animals. On
      average over 6 hours, significant steroid effects were observed for left
      ventricular peak systolic pressure, mm Hg (CON, 85 +/- 2; CON-S, 98 +/- 3; TX, 74
      +/- 3; TX-S, 91 +/- 2); global stroke work, mJoule x cm(-2) (CON, 4.69 +/- 0.21;
      CON-S, 5.88 +/- 0.32; TX, 2.27 +/- 0.17; TX-S, 4.23 +/- 0.16); and peak rate of
      pressure relaxation (-dP/dt(max)), mm Hg/msec (CON, 1.23 +/- 0.05; CON-S, 1.44 +/
      0.08; TX, 0.60 +/- 0.03; TX-S, 2.04 +/- 0.13). Steroid pretreatment produced
      more stable recovery for transplanted animals. All five TX-S animals could be
      removed from inotropic support and had stable function for 6 hours. In contrast,
      1 of 5 TX animals could not be removed from inotropic support, and 1 of 5 TX
      hearts failed 3 hours after transplant. Arterial blood PO2 values were
      significantly higher in steroid-treated animals than in nonsteroid treated
      animals. Blood systemic lactate, which was elevated after transplantation,
      returned to control level by 6 hours in the steroid-treated group but not in the
      nonsteroid-treated group. CONCLUSION: Steroid pretreatment of heart donors and
      recipients improved systolic and diastolic function and hemodynamic stability
      after transplantation. In addition, steroid pretreatment improved pulmonary gas
      exchange of control and transplanted animals.

PMID- 9154946
TI  - Proton magnetic resonance spectroscopy of blood plasma in heart transplant
      recipients treated with cyclosporine: an early prognosis test of long-term graft
      tolerance.
AB  - BACKGROUND: Previous results have established the potential interest of proton
      magnetic resonance spectroscopy (MRS) of plasma lipoproteins in the detection of
      rejection processes after heart transplantation. The aim of this study was to
      determine whether MRS can provide a relevant long-term prognosis factor as early
      as 1 week after transplantation. METHODS: Eighteen patients were monitored for a
      mean period of 16 months after transplantation. The ratio of the sum of the MRS
      total line widths (TLW) for lipoprotein moieties, obtained 1 week after
      transplantation and cyclosporine administration, over the same sum obtained on
      the day of transplantation (TLW(8/0)), as well as the ratio between the
      corresponding intensities of methyl and methylene moieties (IR) were used to
      quantify the lipoprotein spectral profile. RESULTS: TLW(8/0), with a cutoff value
      of 0.8, seemed to have the most value in predicting rejection processes (RP)
      several months later. All six patients with no RP (good prognosis) and all five
      patients with three or more RPs (poor prognosis) during the entire 16-month
      follow-up period were correctly detected as early as 8 days after
      transplantation. The seven patients with only one or two RPs, mainly occurring
      during the first months after transplantation, were usually classified by MRS as
      having good prognosis. CONCLUSIONS: The magnetic resonance spectrum depends on
      both qualitative and quantitative variations in the different lipoprotein
      fractions, known to be carriers of cyclosporine. The magnetic resonance spectrum
      could thus be an early expression of the ability of these lipoproteins to
      modulate the cyclosporine-mediated immunosuppression.

PMID- 9154947
TI  - Redistribution of amiodarone in heart transplant recipients treated with the drug
      before operation.
AB  - Seven heart transplant recipients (six men and one woman) treated with oral
      amiodarone 194 +/- 100 mg/day before operation for a period of 30 +/- 48.5 months
      were studied. The myocardial concentrations of amiodarone in the transplanted
      heart peaked in the second posttransplantation week (87.6 +/- 80.7 microg/g
      myocardial tissue) and remained detectable in the twelfth week (10.2 +/- 8.4
      microg/g myocardial tissue). The ratio of myocardial/plasma concentrations peaked
      at the end of the sixth posttransplantation week. In conclusion, amiodarone
      accumulated rapidly in the transplanted myocardium of heart transplant recipients
      treated with the drug before operation and remained detectable for at least 3
      months.

PMID- 9154948
TI  - Dobutamine echocardiography for prediction of ischemic events in heart transplant
      recipients.
AB  - The purpose of this study was to assess the use of dobutamine stress
      echocardiography in predicting cardiac events in heart transplant recipients.
      Dobutamine echocardiography was performed in 63 consecutive heart transplant
      recipients, 52 males and 11 females ranging in age from 12 to 77 years (mean 54),
      undergoing routine yearly evaluation. Twenty-one patients had abnormal wall
      motion at baseline or during dobutamine infusion. Over a mean follow-up of 8
      months (range 4 to 14), there were six major cardiac events: five occurred among
      patients with abnormal echocardiography study results; only one event occurred in
      a patient with a normal echocardiography result. These data suggest that normal
      wall motion during dobutamine echocardiography identifies a subset of heart
      transplant recipients at low risk for development of cardiac events, whereas an
      abnormal study result serves as an important predictor of subsequent cardiac
      events.

PMID- 9154949
TI  - Absence of bradycardic response to apnea and hypoxia in heart transplant
      recipients with obstructive sleep apnea.
AB  - In patients with obstructive sleep apnea, the vagal stimulation caused by
      inspiration against the upper airway obstruction results in sinus bradycardia
      during the apnea followed by a reflex tachycardia at apnea termination. We report
      on five heart transplant recipients with obstructive sleep apnea who demonstrated
      no change in baseline heart rate in spite of marked hemoglobin oxygen
      desaturation, presumably on account of parasympathetic denervation of the
      allograft. Heart transplant recipients with obstructive sleep apnea may be at an
      increased risk of development of potentially fatal ventricular arrhythmias if the
      allograft is unable to respond appropriately to hypoxia. Should cardiac
      parasympathetic reinnervation occur, prospective polysomnography may be a marker
      for this process in these patients.

PMID- 9154950
TI  - Effects of mechanical left ventricular support on right ventricular diastolic
      function.
AB  - BACKGROUND: Previous studies have shown that left ventricular (LV) unloading
      alters right ventricular (RV) systolic mechanics, but the effects of LV assist
      device (LVAD) support on RV diastolic function have not been examined in intact
      subjects. METHODS: Seven closed-chest, sedated dogs were studied after placement
      of a LVAD and 27 myocardial markers; in four animals, a right coronary artery
      occluder was placed to induce acute RV free wall ischemia. Data were recorded
      with the LVAD off and LVAD on before (control) and during RV ischemia. Assessment
      of RV diastolic function included RV myocardial relaxation (time constant of
      isovolumic pressure decay [tau]), RV chamber stiffness (slope of the end
      diastolic pressure-volume relation), and RV filling dynamics (peak filling rate
      and mean filling rate during early diastole). RESULTS: During control, full LVAD
      support did not alter RV tau (104 +/- 67 msec LVAD off versus 109 +/- 49 msec
      LVAD on, p > 0.50), RV diastolic stiffness (0.56 +/- 0.31 versus 0.51 +/- 0.25 mm
      Hg/ml, p > 0.20), peak filling rate (107 +/- 51 versus 119 +/- 82 ml/sec, p >
      0.35) or mean filling rate during early diastole (32 +/- 28 versus 27 +/- 18
      ml/sec, p > 0.40). With right coronary artery occlusion, RV tau rose to 136 +/-
      33 msec (p < 0.001), and RV diastolic stiffness fell to 0.29 +/- 0.13 mm Hg/ml (p
      < 0.005), but there was no change in RV filling rates (p > 0.20). With mechanical
      LV support during acute RV ischemia, there was no additional change in RV tau,
      diastolic stiffness, or filling dynamics (p > 0.20). CONCLUSIONS: In intact
      animals, RV ischemia impaired RV relaxation and decreased chamber stiffness, but
      there was no change in RV filling rates. Mechanical LV support, during the
      control state and with RV ischemia, did not affect RV diastolic performance.

PMID- 9154951
TI  - Influence of panel-reactive antibody on survival and rejection after lung
      transplantation.
AB  - BACKGROUND: Panel-reactive antibody (PRA) is commonly used before thoracic organ
      transplantation to estimate a potential recipient's degree of humoral
      sensitization. METHODS: To assess the influence of an elevated PRA on survival
      and the incidence of rejection in pulmonary transplantation, the records of 247
      patients that underwent single or double lung transplantation were reviewed.
      RESULTS: Twenty-one of 247 patients (8.5%) had PRA values greater than 10%.
      Survival of this population was not significantly different from that of patients
      with low PRA levels: 74% (low PRA) vs 65% (elevated PRA) at 1 year and 58% in
      both groups at 3 years. The acute rejection rates (episodes/first 100 days) for
      the elevated and low PRA groups were 2.1 and 1.9, respectively (p = NS).
      Obliterative bronchiolitis developed in 38.9% of the high and 31.2% of the low
      PRA groups (p = NS). Six of 247 patients had a retrospective positive
      lymphocytotoxic cross-match result; three had PRA values greater than 10%.
      Patients with a positive cross-match result experienced similar survival and
      incidence of rejection as the remainder of the population. Among 957 patients
      evaluated for lung transplantation, 16 (1.7%) had a PRA (with dithiothreitol)
      greater than 15%. All had a history of pregnancy, blood transfusion, connective
      tissue disease, or previous transplantation. CONCLUSIONS: Humoral sensitization
      is uncommon in the lung transplantation population. A modestly elevated PRA does
      not predict survival or the development of acute rejection or bronchiolitis
      obliterans. PRA testing before lung transplantation should be reserved for those
      patients with specific risk factors for humoral sensitization.

PMID- 9154952
TI  - Incidence and significance of noncytomegalovirus viral respiratory infection
      after adult lung transplantation.
AB  - Lower respiratory tract infection is a major cause of morbidity and death after
      lung transplantation. The incidence and significance of noncytomegalovirus viral
      respiratory tract infections has not been reported to date. We report our
      center's experience with these infections.

PMID- 9154953
TI  - Role of hypercholesterolemia in accelerated transplant coronary vasculopathy:
      results of surgical therapy with partial ileal bypass in rabbits undergoing
      heterotopic heart transplantation.
AB  - BACKGROUND: We tested the hypothesis that plasma cholesterol lowering action of
      partial ileal bypass (PIB) is beneficial in mitigating accelerated
      transplantation coronary vasculopathy. METHODS: Forty-one New Zealand white
      rabbits were randomized to receive a normal (n = 21) or 1% cholesterol diet (n =
      20). They underwent heterotopic heart transplantation with sham-PIB (n = 19) or
      PIB (n = 22) and immunosuppression with cyclosporine A (CyA). RESULTS: CyA
      increased plasma cholesterol of rabbits receiving a normal diet. This effect was
      mitigated by PIB (101 +/- 50 mg/dl CyA vs baseline 24 +/- 8, p < 0.001; vs 54 +/-
      25 mg/dl with PIB, p < 0.05). In cholesterol-fed rabbits, PIB decreased plasma
      cholesterol levels (520 +/- 236 mg/dl PIB vs baseline 720 +/- 359, p < 0.05; vs
      1502 +/- 253 mg/dl with sham PIB, p < 0.00001). Coronary arteries (CA) of 21 5
      week survivors were evaluated by light microscopy and digital morphometry. No
      rejection was noted. Histologic study revealed vasculopathy in 3% of 705 native
      and 18% of 654 transplant CA (p < 0.05). Graft vasculopathy (GV) was present in
      25% of 365 CA of sham-PIB and 10% of 289 CA of PIB rabbits (p = 0.07). In
      cholesterol-fed rabbits, GV was characterized by fatty proliferative lesions in
      75% of 91 pathologic CA of sham and 21% of 28 pathologic CA of PIB rabbits (p <
      0.05). Graft intimal hyperplasia was not correlated with cholesterol intake or
      PIB and was present in 18 of 119 pathologic CA. CONCLUSIONS: GV was characterized
      by fatty intimal proliferation, fibrous intimal hyperplasia, and a "mixed type."
      Fibrous intimal hyperplasia developed in native and transplanted hearts, and CyA
      seemed to promote this state. Hypercholesterolemia promoted fatty proliferative
      lesions, worsening GV. PIB significantly decreased total cholesterol and retarded
      fatty proliferation of CA of native and transplanted hearts but did not prevent
      intimal hyperplastic vasculopathy. Therapy of hypercholesterolemia is recommended
      to at least mitigate the fatty intimal proliferation of GV.

PMID- 9154954
TI  - Aspergillus osteomyelitis after heart-lung transplantation.
AB  - Aspergillus osteomyelitis is a severe complication of invasive aspergillosis.
      Fewer than 15 cases have been observed after solid organ transplantation. We
      describe a case of Aspergillus osteomyelitis of the ilium after heart-lung
      transplantation with favorable outcome after medical treatment.

PMID- 9154955
TI  - Reperfusion injury in single-lung transplant recipients with pulmonary
      hypertension and emphysema.
AB  - BACKGROUND: The early postoperative course of single-lung transplant recipients
      depends on the recipient's underlying lung pathophysiology and the degree of
      ischemic-reperfusion injury. We examined the effect of pulmonary hemodynamics and
      preoperative diagnosis on early allograft function and the effects of pulmonary
      hemodynamics, allograft blood flow, and chest radiographs on length of mechanical
      ventilation and intensive care unit length of stay. METHODS: We retrospectively
      collected data on 30 single-lung transplant recipients, 15 each with
      pretransplantation pulmonary hypertension and emphysema. Blood flow to the
      allografts was quantitated by perfusion scans obtained on the first postoperative
      day. Chest radiographs were graded for reperfusion injury. Pulmonary and
      hemodynamic data, gas exchange parameters, duration of mechanical ventilation,
      and intensive care unit stay were recorded. RESULTS: Patients with pulmonary
      hypertension had a prolonged intensive care unit stay compared with emphysema
      patients, but pulmonary artery pressures were not quantitatively related to
      duration of ventilation during the intensive care unit stay. There was no
      difference in the severity of allograft infiltrate between the emphysema and
      pulmonary hypertensive patients. The day 1 chest radiograph score was highly
      predictive of an intensive care unit stay of > or = 7 days, although the
      threshold score of those with pulmonary hypertension was significantly lower than
      in emphysema patients. Allograft blood flow and pulmonary hypertension were not
      contributors to early graft dysfunction. Allograft perfusion decreased with
      increasing radiographically demonstrated infiltrate in those with emphysema but
      not in those with pulmonary hypertension. CONCLUSIONS: Elevated allograft blood
      flow and pressures do not exacerbate radiographically confirmed reperfusion
      injury. Reperfusion injury is the major cause of early respiratory morbidity
      after single-lung transplantation. Allograft perfusion in emphysema patients
      decreases in response to reperfusion injury, but pulmonary hypertension patients
      remain almost entirely dependent on allograft function, even with severe chest
      radiograph scores. This may be an important mechanism by which single-lung
      transplant recipients with emphysema, unlike those with pulmonary hypertension,
      are able to mitigate the degree of respiratory impairment associated with
      reperfusion injury.

PMID- 9154956
TI  - Delayed reversal of impaired metabolic vasodilation in patients with end-stage
      heart failure during long-term circulatory support with a left ventricular assist
      device.
AB  - BACKGROUND: Whether increased cardiac output during chronic circulatory support
      with a left ventricular assist device (LVAD) is associated with improved
      metabolic vasodilation in the peripheral circulation of patients with congestive
      heart failure is unknown. METHODS: Forearm blood flow, determined by venous
      occlusion plethysmography, mean arterial pressure, and cardiac output were
      measured at rest and after 5 minutes of arterial occlusion (a maximal metabolic
      vasodilatory stimulus) in 14 patients with severe heart failure before LVAD
      implantation, and in the early (<4 weeks) and late (8 to 12 weeks) postoperative
      recovery phases after LVAD implantation. Nine normal subjects served as controls.
      Vascular conductance was calculated as the ratio of forearm blood flow and mean
      arterial pressure. RESULTS: Mean arterial pressure and cardiac output increased
      to normal values in the early and late recovery phases after LVAD implantation.
      Resting forearm blood flow and vascular conductance were similar to normal
      subjects in the early and late recovery phases after LVAD implantation. Peak
      forearm blood flow and vascular conductance were significantly less than control
      subjects in the early preoperative recovery phase (p < 0.05) but were similar to
      control subjects in the late postoperative recovery phase after LVAD
      implantation. CONCLUSIONS: In spite of early normalization of cardiac output,
      mean arterial pressure, and resting forearm blood flow during chronic circulatory
      support with the LVAD, peak forearm blood flow, and peak vascular conductance did
      not increase to values similar to those observed in normal subjects until the
      late postoperative recovery period. The delayed effect of the LVAD on metabolic
      vasodilation may be related to flow-dependent changes in the peripheral
      vasculature of patients with heart failure.

PMID- 9154957
TI  - Effects of fosinopril on the blood pressure and lipid profile of patients
      undergoing heart transplantation.
AB  - PURPOSE: The purpose of this study was to determine whether the angiotensin
      converting enzyme inhibitor, fosinopril, has an antihypertensive effect in
      patients undergoing heart transplantation (HT), as well as any action on lipid
      levels (total cholesterol and its fractions, triglycerides and lipoprotein[a]
      [Lp(a)]). METHODS: The study included 15 male patients aged 54 +/- 10 years; nine
      had undergone transplantation as a result of ischemic heart disease and six as a
      result of idiopathic dilated cardiomyopathy. The average time from the heart
      transplantation was 12 +/- 4 months. Six transplantations were performed after
      antidiabetic treatment, and six were performed with patients receiving a
      hypolipidemic agent. The subjects of the study were patients with mild to
      moderate hypertension who were receiving antihypertensive treatment; the
      antihypertensive medications were withdrawn during 7 days. Periodic blood
      pressure and basal analytic determinations were then carried out after 4 and 12
      weeks of treatment and 7 days after withdrawal of the antihypertensive
      medications. RESULTS: Significant differences (p < 0.05) were found in the
      systolic blood pressure (SBP) and diastolic blood pressure (DBP) compared with
      the basal values (SBP 160 +/- 11 mm Hg; DBP 98 +/- 8 mm Hg), after 4 weeks of
      treatment (SBP 138 +/- 10 mm Hg; DBP 83 +/- 7 mm Hg), and after 12 weeks of
      treatment (SBP 137 +/- 12 mm Hg; DBP 84 +/- 9 mm Hg); these differences persisted
      7 days after the drug was withdrawn (SBP 150 +/- 12 mm Hg; DBP 95 +/- 10 mm Hg).
      The total cholesterol, low-density lipoprotein (LDL) cholesterol, and Lp(a)
      dropped compared with the basal levels (total cholesterol 184 +/- 19, LDL
      cholesterol 123 +/- 13, Lp(a) 29 +/- 12), after 4 weeks (total cholesterol 172 +/
      21, LDL cholesterol 116 +/- 8, Lp(a) 26 +/- 8) and after 12 weeks (total
      cholesterol 169 +/- 20, LDL cholesterol 115 +/- 6, Lp(a) 25 +/- 8) of treatment,
      returning to basal values on withdrawal of the drug. CONCLUSIONS: Fosinopril is a
      useful drug for the treatment of the mild to moderate arterial hypertension of
      heart transplant recipients, in addition to being capable of reducing the serum
      levels of total cholesterol, LDL cholesterol, and Lp(a). It should therefore be
      considered a first-line antihypertensive agent with beneficial effects on the
      lipid profile.

PMID- 9154958
TI  - Prognostic value of pulmonary hypertension in patients with chronic interstitial
      lung disease referred for lung or heart-lung transplantation.
AB  - BACKGROUND: The purpose of this study was to identify precise and reliable
      prognostic parameters in patients affected by serious chronic interstitial lung
      disease, who were undergoing screening for lung or heart-lung transplantation.
      METHODS: Hemodynamic and respiratory function parameters of 67 patients (43 with
      idiopathic pulmonary fibrosis, 18 with histiocytosis X, and 6 with
      lymphangioleiomyomatosis) undergoing clinical screening for lung transplantation.
      RESULTS: Statistical analysis showed that hemodynamic and respiratory function
      parameters in patients affected by histiocytosis X and idiopathic pulmonary
      fibrosis were not related to survival time. Moreover, the degree of pulmonary
      hypertension showed no correlation between respiratory function parameters in all
      the groups of diseases examined. Patients affected with histiocytosis X, even
      with higher degrees of pulmonary hypertension, had a better survival rate (p <
      0.0005) compared with patients with idiopathic pulmonary fibrosis. CONCLUSIONS:
      Hemodynamic and respiratory parameters obtained during the clinical screening for
      lung transplantation do not predict survival and cannot be used as prognostic
      indicators.

PMID- 9154959
TI  - Epidemiologic evidence of transmission of donor-related bacterial infection
      through a transplanted heart.
AB  - This study describes a patient who had fulminant infectious myocarditis as a
      result of methicillin-resistant Staphylococcus aureus after receiving a heart
      transplant from an infected donor. There was complete concordance of typing
      results between donor and recipient strains that were different from the 20
      isolates with which they were compared. Molecular epidemiologic study provided
      compelling evidence that a transplanted organ can transmit a bacterial infection
      from the donor to the recipient.

PMID- 9154960
TI  - Extracorporeal membrane oxygenation for early graft dysfunction in lung
      transplantation: a case report.
AB  - Although extracorporeal membrane oxygenation (ECMO) has become standard treatment
      for neonatal respiratory failure, the results of ECMO in adults have been less
      encouraging. With technical improvements in membrane oxygenators and revised ECMO
      protocols, there has been renewed interest in ECMO for adults with severe acute
      respiratory failure. However, few cases of ECMO as an adjunct to adult lung
      transplantation have been reported. We present the case of a 20-year-old woman
      with cystic fibrosis who underwent bilateral single lung transplantation. She had
      development of severe graft dysfunction in the immediate postoperative period
      requiring support with ECMO for stabilization.

PMID- 9154961
TI  - Ondansetron eliminates nausea and vomiting associated with prostacyclin in a
      patient awaiting lung transplantation.

PMID- 9154962
TI  - Sequential use of G-CSF and GM-CSF after heart-lung transplantation.

PMID- 9154964
TI  - Novel heterocyclic-fused pyridazinones as potent and selective phosphodiesterase
      IV inhibitors.
AB  - A series of 6-aryl-4,5-heterocyclic-fused pyridazinones were designed and
      synthesized as selective phosphodiesterase (PDE) IV inhibitors. Biological
      evaluation of these compounds demonstrated a good selectivity profile toward the
      PDE IV family and greatly attenuated affinity for the Rolipram high-affinity
      binding site that seems to be responsible for undesiderable side effects.
      Structure-activity relationships (SARs) studies showed that the presence of an
      ethyl group at pyridazine N-2 is associated with the best potency and selectivity
      profile.

PMID- 9154963
TI  - Discovery and synthesis of [6-hydroxy-3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]-2-(4
      hydroxyphenyl)]b enzo[b]thiophene: a novel, highly potent, selective estrogen
      receptor modulator.
AB  - Raloxifene,[2-(4-hydroxyphenyl)-6-hydroxybenzo[b]thien-3-yl] [4-[2-(1
      piperidinyl)ethoxy]phenyl]methanone hydrochloride (2), is representative of a
      class of compounds known as selective estrogen receptor modulators (SERMs) that
      possess estrogen agonist-like actions on bone tissues and serum lipids while
      displaying potent estrogen antagonist properties in the breast and uterus. As
      part of ongoing SAR studies with raloxifene, we found that replacement of the
      carbonyl group with oxygen ([6-hydroxy-3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]-2
      (4-hydroxyphenyl)]b enzo[b]thiophene hydrochloride, 4c) resulted in a substantial
      (10-fold) increase in estrogen antagonist potency relative to raloxifene in an in
      vitro estrogen dependent cell proliferation assay (IC50 = 0.05 nM) in which human
      breast cancer cells (MCF-7) were utilized. In vivo, 4c potently inhibited the
      uterine proliferative response to exogenous estrogen in immature rats following
      both sc and oral dosing (ED50 of 0.006 and 0.25 mg/kg, respectively). In
      ovariectomized aged rats, 4c produced a significant maximal decrease (45%) in
      total cholesterol at 1.0 mg/kg (p.o.) and showed a protective effect on bone
      relative to controls with maximal efficacy at 1.0 mg/kg (p.o.). These data
      identify 4c as a novel SERM with greater potency to antagonize estrogen in
      uterine tissue and in human mammary cancer cells compared to raloxifene,
      tamoxifen or ICI-182,780.

PMID- 9154965
TI  - Conformationally constrained [p-(omega-aminoalkyl)phenacetyl]-L-seryl-L-lysyl
      dipeptide amides as potent peptidomimetic inhibitors of Candida albicans and
      human myristoyl-CoA:protein N-myristoyl transferase.
AB  - MyristoylCoA:protein N-myristoyltransferase (NMT) covalently attaches the 14
      carbon saturated fatty acid myristate, via an amide bond, to the N-terminal
      glycine residues of a variety of cellular proteins. Genetic studies have shown
      that NMT is essential for the viability of the principal fungal pathogens which
      cause systemic infection in immunosuppressed humans and hence is a target for
      development of fungicidal drugs. We have generated a class of potent
      peptidomimetic inhibitors of the NMT from one such fungal pathogen, Candida
      albicans. The N-terminal tetrapeptide from a substrate analog inhibitor, ALYASKL
      NH2, was replaced with an omega-aminoalkanoyl moiety having an optimal 11-carbon
      chain for inhibition (11-aminoundecanoyl-SKL-NH2, 3a, IC50 = 1.2 +/- 0.14
      microM). A series of replacements for the C-terminal Leu established that
      residues containing a lipophilic side chain were most effective, with
      cyclohexylalanine having the greatest potency (3g, IC50 = 0.36 +/- 0.06 microM).
      Removal of the carboxamide moiety led to a metabolically stable dipeptide
      inhibitor containing an N-(cyclohexylethyl)lysinamide (17e, IC50 = 0.11 +/- 0.03
      microM). Partial rigidification of the flexible aminoundecanoyl chain produced
      the dipeptide p-(omega-aminohexyl)phenacetyl-L-seryl-L-lysyl-N-(cyclohexyleth
      yl)amide (26b, IC50 = 0.11 +/- 0.04 microM). Subsequent incorporation of an alpha
      methyl substituent into 26b provided the dipeptide analog [2-[p-(omega
      aminohexyl)phenyl]propionyl]-L-seryl-L-lysyl-N-(cyclohex ylethyl)amide, a very
      potent inhibitor (48, IC50 = 0.043 +/- 0.006 microM), which retained the three
      essential elements required for recognition by the acyl transferase's peptide
      binding site.

PMID- 9154966
TI  - Synthesis and structure-activity relationships of 17beta-substituted 14beta
      hydroxysteroid 3-(alpha-L-rhamnopyranoside)s: steroids that bind to the digitalis
      receptor.
AB  - The preparation of 17beta-substituted 14beta-hydroxysteroid C-3 alpha-L
      rhamnopyranosides is described. These derivatives have a 14beta,20-ether,
      14beta,20-lactone, or 17beta-CH2CH2OH, -CH2CH2NH2, -CH=CHNO2(E), -CH=CHCOOH(E), 
      CH(OH)CH2NO2(R), -CH(OMe)CH2NO2(R), -CH2-CH2COOH, or -CH(OH)CH2NH2(R) group.
      Derivatives were assayed in a radioligand binding assay for [3H]ouabain in
      membranes from canine heart muscle. The digitalis "receptor" comprises isoenzymes
      of the ion-pumping enzyme, Na+,K+-ATPase. The 17beta-CH=CHNO2(E), 17beta
      CH=CHCOOH(E), and 17beta-CH(OMe)CH2NO2(R) derivatives were the most potent and
      equivalent to ouabain with low-nanomolar IC50 values. The very potent binding
      affinity of the disubstituted compound 17beta-CH(OMe)CH2NO2(R) further
      demonstrates that 17beta-unsaturated substitution is not required for potent
      binding affinity. This observation may be of value in the separation of
      cardiotonic and cardiotoxic effects. Tosylation of the 17beta-CH2OH, prepared
      from the 17beta-CHO by lithium aluminum hydride reduction, yielded the
      14beta,17beta-ether. Synthesis of the 17beta-CH2COOH gave the epimeric
      14alpha,17alpha- and 14beta,17beta-lactones. Structures have been established by
      NMR analysis.

PMID- 9154968
TI  - Smart region definition: a new way to improve the predictive ability and
      interpretability of three-dimensional quantitative structure-activity
      relationships.
AB  - This report describes a new methodology aimed at grouping 3D-QSAR interaction
      energy descriptors into regions of neighbor variables bearing the same chemical
      and statistical information. These regions represent the structural variability
      of the series better than individual descriptor variables and can advantageously
      replace them in the chemometric analysis. The algorithm used to generate such
      regions is described, together with their application for improving the quality
      of GOLPE variable selection. The method is illustrated on a series of 47 glucose
      analogues, inhibitors of glycogen phosphorylase b, and is shown to improve both
      the predictive ability and the interpretability of the 3D-QSAR models obtained,
      comparing favorably with other methods previously described.

PMID- 9154967
TI  - Dihydro(alkylthio)(naphthylmethyl)oxopyrimidines: novel non-nucleoside reverse
      transcriptase inhibitors of the S-DABO series.
AB  - Novel compounds related to 2-(cyclohexylthio)-3,4-dihydro-5-methyl-6-(3
      methylbenzyl)-4-ox opyrimidine (3c, MC 639) have been synthesized and tested as
      inhibitors of human immunodeficiency virus type-1 (HIV-1). Reaction of thiourea
      with ethyl arylmethylacetoacetates furnished 5-alkyl-6-(arylmethyl)-3,4-dihydro-2
      mercapto-4-oxopyrimidines which were then alkylated at the sulfur atom to afford
      the required 2-alkylthio or 2-cycloalkylthio derivatives (S-DABOs). Chemical
      modifications at N-3, C-4, and C-6 of the pyrimidine ring were attempted with the
      aim of improving antiretroviral activity. In particular, replacement of the
      benzyl group with the 1-naphthylmethyl moiety enhanced the activity of S-DABOs,
      whereas N-3 alkylation and C=O transformation into C=S at position 4 of the
      pyrimidine ring led to compounds devoid of anti-HIV-1 activity. Lower activity
      was generally observed when 1-naphthylmethyl was replaced by the isomeric 2
      naphthylmethyl moiety. The most active compounds showed activity in the low
      micromolar range with EC50 values comparable to that of nevirapine.

PMID- 9154970
TI  - A comparison of structure-activity relationships between spermidine and spermine
      analogue antineoplastics.
AB  - A systematic investigation of the impact of spermidine analogues both in vitro
      and in vivo is described. The study characterizes the effects of these analogues
      on L1210 cell growth, polyamine pools, ornithine decarboxylase, S-adenosyl-L
      methionine decarboxylase, spermidine/spermine N1-acetyltransferase, the
      maintenance of cellular charge, i.e., cationic equivalence associated with the
      polyamines and their analogues, and compares their ability to compete with
      spermidine for transport. The findings clearly demonstrate that the activity of
      the linear polyamine analogues is highly dependent on the length of the triamines
      and the size of the N(alpha),N(omega)-substituents. It appears that there is an
      optimum chain length for various activities and that the larger the
      N(alpha),N(omega)-alkyls, the less active the compound. Metabolic transformation
      including N-dealkylation of these compounds is also evaluated. While there is no
      monotonic relationship between chain length and the ability of the analogue to be
      metabolized, the dipropyl triamines are clearly more actively catabolized than
      the corresponding methyl and ethyl systems. A comparison of the triamines with
      the corresponding tetraamines is made throughout the text regarding both in vitro
      activity against L1210 cells and in vivo toxicity measurements, suggesting that
      several triamine analogues may offer therapeutic advantages over the
      corresponding tetraamines.

PMID- 9154969
TI  - Improved P1/P1' substituents for cyclic urea based HIV-1 protease inhibitors:
      synthesis, structure-activity relationship, and X-ray crystal structure analysis.
AB  - We present several novel P1/P1' substituents that can replace the characteristic
      benzyl P1/P1' moiety of the cyclic urea based HIV protease inhibitor series.
      These substituents typically provide 5-10-fold improvements in binding affinity
      compared to the unsubstituted benzyl analogs. The best substituent was the 3,4
      (ethylenedioxy)benzyl group. Proper balancing of the molecule's lipophilicity
      facilitated the transfer of this improved binding affinity into a superior
      cellular antiviral activity profile. Several analogs were evaluated further for
      protein binding and resistance liabilities. Compound 18 (IC90 = 8.7 nM) was
      chosen for oral bioavailability studies based on its log P and solubility
      profile. A 10 mg/kg dose in dogs provided modest bioavailability with Cmax = 0.22
      microg/mL. X-ray crystallographic analysis of two analogs revealed several
      interesting features responsible for the 3,4-(ethylenedioxy)benzyl-substituted
      analog's potency: (1) Comparing the two complexes revealed two distinct binding
      modes for each P1/P1' substituent; (2) The ethylenedioxy moieties are within 3.6
      A of Pro 81 providing additional van der Waals contacts missing from the parent
      structure; (3) The enzyme's Arg 8 side chain moves away from the P1 substituent
      to accommodate the increased steric volume while maintaining a favorable hydrogen
      bond distance between the para oxygen substituent and the guanidine NH.

PMID- 9154971
TI  - Folate-based inhibitors of thymidylate synthase: synthesis and antitumor activity
      of gamma-linked sterically hindered dipeptide analogues of 2-desamino-2-methyl
      N10-propargyl-5,8-dideazafolic acid (ICI 198583).
AB  - In an effort to synthesize inhibitors of thymidylate synthase (TS) that do not
      undergo polyglutamation, a series of gamma-linked sterically hindered dipeptide
      analogues of 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583)
      was prepared. A methyl, ethyl, or propargyl group was incorporated into the gamma
      glutamyl amide bond of gamma-linked L,L dipeptide derivatives of ICI 198583, such
      as ICI 198583-gamma-L-Glu. In addition, steric bulk was introduced on either side
      of the gamma-glutamyl bond of ICI 198583-gamma-L-Glu or ICI 198583-gamma-L-Ala.
      The resulting dipeptide analogues, e.g., ICI 198583-gamma-MeGlu and ICI 198583
      gamma-Aib, were apparently stable to in vivo hydrolysis but poorer inhibitors of
      TS and L1210 cell growth. However, introduction of 7-Me, 2'-F substitution into
      the quinazoline nucleus gave significant improvement in the inhibitory activity
      against thymidylate synthase. Compounds 28-30, the 7-Me, 2'-F derivatives of ICI
      198583-gamma-MeGlu, ICI 198583-gamma-EtGlu, and ICI 198583-gamma-PgGlu,
      respectively, were potent inhibitors of TS (K(iapp) = 0.21-1.1 nM) and L1210 cell
      growth (IC50 = 0.05-0.34 microM) and were similar to that seen with the most
      potent gamma-linked L,D dipeptide derivatives of ICI 198583 previously
      synthesized. Furthermore, the low cross-resistance ratios for the
      L1210:R(D1694)/L1210 cell line indicated that 28-30 do not undergo
      polyglutamation.

PMID- 9154972
TI  - Synthesis, antiviral activity, and biological properties of vinylacetylene
      analogs of enviroxime.
AB  - A series of vinylacetylene analogs of Enviroxime (1) was synthesized. The new
      compounds are potent inhibitors of poliovirus in tissue culture. Cross
      sensitivity with Enviroxime-derived mutants shows that the new compounds have the
      same mechanism of action as Enviroxime, which involves the viral 3A protein. In
      studies with Rhesus monkeys, the p-fluoro derivative 12 was found to be unique in
      providing oral bioavailability. Metabolism studies using hepatic microsomes
      suggest that this procedure would be a useful in vitro method for selecting the
      appropriate animal model for testing oral absorption. Compound 12 was found to be
      efficacious by oral administration in treating a Coxsackie A21 infection in CD-1
      mice.

PMID- 9154973
TI  - Tyrosine kinase inhibitors. 11. Soluble analogues of pyrrolo- and
      pyrazoloquinazolines as epidermal growth factor receptor inhibitors: synthesis,
      biological evaluation, and modeling of the mode of binding.
AB  - A new route to N-1-substituted pyrazolo- and pyrroloquinazolines has been
      developed from the known quinazolones 19 and 23, via conversion to the
      corresponding thiones, S-methylation to the thioethers, N-1-alkylation, and
      coupling with 3-bromoaniline. C-3-Substituted pyrroloquinazolines were prepared
      by Mannich base chemistry. A series of compounds bearing solubilizing side chains
      at these positions has been prepared and evaluated for inhibition of the tyrosine
      kinase activity of the isolated epidermal growth factor receptor (EGFR) and of
      its autophosphorylation in EGF-stimulated A431 cells. Several analogues,
      particularly C-3-substituted pyrroloquinazolines, retained high potency in both
      assays. A model for the binding of the general class of 4-anilinoquinazolines to
      the EGFR was constructed from structural information (particularly for the
      catalytic subunit of the cAMP-dependent protein kinase) and structure-activity
      relationships (SAR) in the series. In this model, the pyrrole ring in
      pyrroloquinazolines (and the 6- and 7-positions of quinazoline and related
      pyridopyrimidine inhibitors) occupies the entrance of the ATP binding pocket of
      the enzyme, with the pyrrole nitrogen located at the bottom of the cleft and the
      pyrrole C-3 position pointing toward a pocket corresponding to the ribose binding
      site of ATP. This allows considerable bulk tolerance for C-3 substituents and
      lesser but still significant bulk tolerance for N-1 substituents. The observed
      high selectivity of these compounds for binding to EGFR over other similar
      tyrosine kinases is attributed to the 4-anilino ring binding in an adjacent
      hydrophobic pocket which has an amino acid composition unique to the EGFR. The
      SAR seen for inhibition of the isolated enzyme by the pyrazolo- and
      pyrroloquinazolines discussed here is fully consistent with this binding model.
      For the N-1-substituted compounds, inhibition of autophosphorylation in A431
      cells correlates well with inhibition of the isolated enzyme, as seen previously
      for related pyridopyrimidines. However, the C-3-substituted pyrroloquinazolines
      show unexpectedly high potencies in the autophosphorylation assay, making them of
      particular interest.

PMID- 9154975
TI  - Binding affinities for sulfonamide inhibitors with human thrombin using Monte
      Carlo simulations with a linear response method.
AB  - The binding of sulfonamide inhibitors to human thrombin is examined to evaluate
      the viability of calculating free energies of binding, deltaGb, utilizing Monte
      Carlo (MC) statistical mechanics with a linear response approach. Coulombic and
      van der Waals energy components determined from MC simulations of the bound and
      unbound inhibitors solvated in water plus a solvent-accessible surface area term,
      as an index for cavity formation, were correlated with the free energies of
      binding for the inhibitor MD-805 and six derivatives. The best correlations yield
      an average error of 0.8 kcal/mol for the seven binding affinities, which cover an
      observed range of 6.0 kcal/mol. The MC simulations also provided insights into
      the interactions occurring in the active site and the origins of variations in
      deltaGb. Equatorial placement of the carboxylate group at C2 in the piperidine
      ring of the inhibitors causes electrostatic destabilization with the side chain
      of Glu-H192, while axial disposition of the C4-methyl group reduces favorable
      hydrophobic interactions in the P-pocket of the enzyme.

PMID- 9154974
TI  - Inhibition of thyroid hormone uptake by calcium antagonists of the
      dihydropyridine class.
AB  - A series of substituted 4-phenyl-1,4-dihydropyridines 2a-m was tested for their
      inhibitory effects on L-triiodothyronine (L-T3) uptake by human HepG2 hepatoma
      cells. The most potent compounds were the nitro-substituted derivatives 2,6
      dimethyl-4-(4'-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-ethyl
      ester 5-methyl ester (2m) and the well-known calcium antagonists nitrendipine
      (2k) and nifedipine (2j) with an uptake inhibition between 80.5 and 85.8% at an
      application dose of 10(-5) M. On the basis of a theoretical conformational
      analysis (ab initio MO theory, molecular mechanics, molecular dynamics) of the
      dihydropyridine derivatives, a unifying stereochemical concept was derived
      postulating an angular arrangement of the two rings where the phenyl ring of the
      calcium antagonists, which corresponds to the outer phenyl ring of the thyroid
      hormones, is bisecting the dihydropyridine ring as a prerequisite for inhibitory
      potency. This model includes also inhibitors of the N-phenylanthranilic acid
      type. The interaction of the calcium antagonists with transthyretin (TTR) is
      discussed in relation to thyroid hormones. The influence of hydrophobicity was
      estimated by the experimental determination of the 1-octanol/water partition
      coefficients.

PMID- 9154976
TI  - Preparation and anti-HIV activity of N-3-substituted thymidine nucleoside
      analogs.
AB  - A series of 22 derivatives of AZT substituted at the N-3 position of the thymine
      base were prepared and evaluated for anti-HIV activity in cell culture (Lai
      strain of HIV-1 in CEM-c113 cells). The AZT analogs bearing a N-3 amino group
      (7), a hydroxyalkyl chain (12f), and a phosphonomethyl (12k) substituent
      displayed activities in the 0.045-0.082 microM range. The analogs 12d, 12e, 12q,
      15, and 19 were active at <0.5 microM concentration. Compound 18 in which two
      molecules of AZT are connected at N-3 via a two-carbon link and "dimer" 11 also
      displayed significant activity. To obtain information concerning the mechanism of
      RT inhibition by these AZT analogs, compounds 7, 12d, 12e, and 12q were incubated
      with recombinant HIV-1 RT in the presence of poly(A)-oligo[dT(12-18)] and poly(C)
      oligo[dG(12-18)] template-primers. In contrast to AZT-TP (control), none of these
      nucleosides displayed any significant inhibition of RT in the recombinant enzyme
      assay, indicating that phosphorylation is a necessary prerequisite for activity.

PMID- 9154977
TI  - Unraveling DNA helicases from plant cells.

PMID- 9154978
TI  - Constitutive non-inducible expression of the Arabidopsis thaliana Nia 2 gene in
      two nitrate reductase mutants of Nicotiana plumbaginifolia.
AB  - We have isolated a haploid cell line of N. plumbaginifolia, hNP 588, that is
      constitutive and not inducible for nitrate reductase. Nitrate reductase mutants
      were isolated from hNP 588 protoplasts upon UV irradiation. Two of these nitrate
      reductase-deficient cell lines, nia 3 and nia 25, neither of which contained any
      detectable nitrate reductase activity, were selected for complementation studies.
      A cloned Arabidopsis thaliana nitrate reductase gene Nia 2 was introduced into
      each of the two mutants resulting in 56 independent kanamycin-resistant cell
      lines. Thirty of the 56 kanamycin-resistant cell lines were able to grow on
      nitrate as the sole nitrogen source. Eight of these were further analyzed for
      nitrate reductase enzyme activity and nitrate reductase mRNA production. All
      eight lines had detectable nitrate reductase activity ranging from 7% to 150% of
      wild-type hNP 588 callus. The enzyme activity levels were not influenced by the
      nitrogen source in the medium. The eight lines examined expressed a constitutive,
      non-inducible 3.2 kb mRNA species that was not present in untransformed controls.

PMID- 9154979
TI  - Alternate paths of evolution for the photosynthetic gene rbcL in four
      nonphotosynthetic species of Orobanche.
AB  - We have determined the nucleotide sequence for the Rubisco large subunit from
      four holoparasitic species of Orobanche. Intact open reading frames are present
      in two species (O. corymbosa and O. fasciculata), whereas the remaining species
      (O. cernua and O. ramosa) have rbcL pseudogenes. Sequences for rbcL 5'-UTRs from
      species of Orobanche have few changes in the promoter and ribosome binding sites
      compared to photosynthetic higher plants. Comparison of rbcL 3'-UTR sequences for
      Nicotiana, Ipomoea, Cuscuta, and Orobanche reveal that nucleotide sequences from
      parasitic plants have regions capable of forming stem-loop structures, but 56-69
      nt are deleted upstream of the stem-loop in the parasitic plants compared to
      their photosynthetic relatives. Although rbcL pseudogenes of O. cernua and O.
      ramosa have many large and small deletions, few indels are shared in common,
      implying that their common ancestor probably had an intact rbcL reading frame.
      Intact rbcL reading frames in O. corymbosa and O. fasciculata retain a bias of
      synonymous over nonsynonymous substitutions and deduced protein sequences are
      consistent with potentially functional Rubisco large subunit proteins. A
      conservative model of random substitution processes in pseudogene sequences
      estimates that the probability is low (P < 0.028) that these sequences would
      retain an open reading frame by chance. Species of Orobanche have either had
      recent photosynthetic ancestors, implying multiple independent losses of
      photosynthesis in this genus, or the rbcL gene may serve an unknown function in
      some nonphotosynthetic plants.

PMID- 9154980
TI  - Molecular cloning, structure and expression of an elicitor-inducible chitinase
      gene from pine trees.
AB  - We have cloned, sequenced, and examined the expression of genes from pine trees
      that appear to encode extracellular class II chitinase. Nucleotide sequence
      analysis indicates a coding sequence composed of three exons interrupted by two
      introns at locations identical to those found in other chitinase genes that
      possess introns. One of the genes, Pschi4, potentially encodes a protein that
      shares 62% amino acid sequence identity through the catalytic domain with class
      II chitinase from tobacco. In contrast, Pschi1 contains a stop codon in the first
      exon and may be a pseudogene. Pschi4 genes are conserved in several species of
      pine, and appear to comprise a small multigene family. Treatment of pine cell
      suspension cultures with the general elicitor chitosan induced Pschi4 expression.
      The regulatory sequences associated with the Pschi4 gene were sufficient to
      direct chitosan-inducible expression of Pschi4 in transgenic tobacco plants,
      which indicates that Pschi4 is an actively expressed member of the multigene
      family. The observation that the Pschi4 gene from pine (a gymnosperm) was
      appropriately regulated by chitosan in tobacco (an angiosperm) suggests that the
      signaling pathways that mediate chitosan-induced transcription are highly
      conserved in the plant kingdom.

PMID- 9154981
TI  - Enhanced expression in tobacco of the gene encoding green fluorescent protein by
      modification of its codon usage.
AB  - The gene encoding green fluorescent protein (GFP) from Aequorea victoria was
      resynthesized to adapt its codon usage for expression in plants by increasing the
      frequency of codons with a C or a G in the third position from 32 to 60%. The
      strategy for constructing the synthetic gfp gene was based on the overlap
      extension PCR method using 12 long oligonucleotides as the starting material and
      as primers. The new gene contains 101 silent nucleotide changes compared to its
      wild-type counterpart used in this study. Several transgenic tobacco lines
      containing the wild-type gfp gene contained minute amounts of a smaller protein
      cross-reacting with GFP antiserum, whereas only one protein of the expected size
      was found in transgenics with the synthetic gfp gene. The smaller protein was
      probably encoded by a truncated gfp mRNA created by splicing of a 84 bp cryptic
      intron as detected by a reverse transcription-PCR technique. A comparison of GFP
      production in transgenics with the wild-type and the synthetic gfp gene under the
      control of the enhanced CaMV 35S promoter showed that the large-scale alterations
      in the gfp gene increased the frequency of high expressors in the transgenic
      population but hardly changed the maximum GFP concentrations. The latter
      phenomenon may be attributed to a reduced regeneration capacity of transformed
      cells with higher GFP concentrations.

PMID- 9154982
TI  - Differential regulation of chloroplast gene expression in Chlamydomonas
      reinhardtii during photoacclimation: light stress transiently suppresses
      synthesis of the Rubisco LSU protein while enhancing synthesis of the PS II D1
      protein.
AB  - Transfer of Chlamydomonas reinhardtii cells grown photoautotrophically in low
      light to higher light intensities has a dramatic transient effect on the
      differential expression of the two major chloroplast encoded photosynthetic
      proteins. Synthesis of the D1 protein of Photosystem II increases more than 10
      fold during the first six hours in high light (HL), whereas synthesis of the
      large subunit (LSU) of Rubisco drops dramatically within 15 min and only
      gradually resumes at about 6 h. Synthesis of the chloroplast-encoded ATP synthase
      beta subunit, the nuclear-encoded Rubisco small subunit and the nuclear-encoded
      beta-tubulin is not noticeably affected. Up regulation of psbA mRNA translation
      accounts for a substantial fraction of the increased D1 synthesis, since
      accumulation of psbA mRNA increases 4.2- and 6.3-fold less than D1 synthesis at 6
      and 18 h in HL. Down-regulation of LSU synthesis is not correlated with a
      reduction in the steady-state level of the rbcL transcript. Primer extension
      mapping of the 5' ends of the rbcL mRNAs reveals transcripts with start points
      located at -93 and -168 relative to the first translated ATG. Transfer of low
      light (LL)-grown cells to HL temporarily decreases the ratio of the -93 to -168
      transcripts, but this ratio normalizes after 6 h in HL, coincident with the
      recovery in the synthesis of LSU. These several distinct effects of temporary
      light stress were correlated with a rapid, sustained increase in the reduction
      state of QA, a transient decline in photosynthetic efficiency, a less rapid drop
      in total chlorophyll content and a delay in cell division.

PMID- 9154983
TI  - mRNA stability and localisation of the low-temperature-responsive barley gene
      family blt14.
AB  - Transcription and translation inhibitors have been used to investigate the role
      of mRNA stability in the low-temperature-regulated expression of the post
      transcriptionally controlled low temperature responsive barley gene family,
      blt14. Genomic clones (blt14.1, blt14.2) representing additional members of the
      blt14 gene family have been isolated and sequenced. Gene specific probes have
      been used to analyse the spatial expression of each individual member of the
      blt14 gene family. Findings indicate that all of the genes are responsive to low
      temperature, but the organ distribution is different for each gene. The results
      indicate that blt14.0 mRNA is stabilised by a low-temperature-dependent protein
      factor. Taken together, the results suggest that organ-specific post
      transcriptional mechanisms are important in the low-temperature regulation of
      blt14 gene expression.

PMID- 9154984
TI  - The presence of a Sar1 gene family in Brassica campestris that suppresses a yeast
      vesicular transport mutation Sec12-1.
AB  - Two new members (Bsar1a and Bsar1b) of the Sar1 gene family have been identified
      from a flower bud cDNA library of Brassica campestris and their functional
      characteristics were analyzed. The two clones differ from each other at 14
      positions of the 193 amino acid residues deduced from their coding region. The
      amino acid sequences of Bsar1a and Bsar1b are most closely related to the Sar1
      family, genes that function early in the process of vesicle budding from the
      endoplasmic reticulum (ER). The sequences contain all the conserved motifs of the
      Ras superfamily (G1-G4 motifs) as well as the distinctive structural feature near
      the C-terminus that is Sar1 specific. Our phylogenetic analysis confirmed that
      these two clones can indeed be considered members of the Sar1 family and that
      they have a close relationship to the ARF family. The Bsar1 proteins, expressed
      in Escherichia coli, cross-reacted with a polyclonal antibody prepared against
      Saccharomyces cerevisiae Sar1 protein. It also exhibited GTP-binding activity.
      Genomic Southern blot analysis, using the 3'-gene-specific regions of the Bsar1
      cDNAs as probes, revealed that the two cDNA clones are members of a B. campestris
      Sar1 family that consists of 2 to 3 genes. RNA blot analysis, using the same gene
      specific probes, showed that both genes are expressed with similar patterns in
      most tissues of the plant, including leaf, stem, root, and flower buds.
      Furthermore, when we placed the two Bsar1 genes under the control of the yeast
      pGK1 promoter into the temperature-sensitive mutant yeast strain S. cerevisiae
      Sec12-1, they suppressed the mutation which consists of a defect in vesicle
      transport. The amino acid sequence similarity, the GTP-binding activity, and the
      functional suppression of the yeast mutation suggest that the Bsar1 proteins are
      functional homologues of the Sar1 protein in S. cerevisiae and that they may
      perform similar biological functions.

PMID- 9154985
TI  - High content, size and distribution of single-stranded DNA in the mitochondria of
      Chenopodium album (L.).
AB  - Mitochondrial (mt) DNA of higher plants is unique in its large size and
      complexity. We report here a hitherto unknown feature, the presence of large
      quantities of single-stranded (ss) DNA. About 2.0-8.5% of the chromosomal mtDNA
      from a suspension culture (depending on the growth stage) and 6.5% of the
      chromosomal mtDNA from whole plants of Chenopodium album were found to be in ss
      form by dot-blot hybridization after neutral transfer. Similar amounts of ss
      mtDNA were observed by binding of the single-strand binding (SSB) protein of
      Escherichia coli under the electron microscope. Significantly less ssDNA was
      found in plastids of C. album and in E. coli cells. We observed ss regions
      between 100 and 22,800 bases distributed in the mt genome spaced from 0.5-100 kb
      apart. After pulsed-field gel electrophoresis (PFGE), the well-bound fraction of
      mtDNA (found to consist of circular, sigma-shaped and rosette-like molecules),
      contained the major part of ssDNA as opposed to the migrating linear molecules.
      Digestion of mtDNA by ss-specific nucleases followed by PFGE mobilized all well
      bound DNA and correspondingly increased the quantity of migrating linear DNA
      molecules. The implications of ssDNA for the structural organization on plant mt
      genomes are discussed.

PMID- 9154986
TI  - Copia-like retrotransposons in rice: sequence heterogeneity, species distribution
      and chromosomal locations.
AB  - Degenerated oligonucleotide primers were used to amplify, clone, and analyze
      sequence heterogeneity and chromosomal distribution of 23 PCR fragments
      corresponding to the reverse transcriptase domain of copia-like retrotransposons
      in rice. Of the 23 fragments 22 could be aligned by their deduced amino acid
      sequences and were divided into 6 groups according to the phylogenetic and
      Southern blot analyses. Amino acid sequence differences among the 22 aligned
      fragments ranged from 1 to 64%. Southern blot analysis of 10 rice accessions
      including indica, japonica and common wild rice, using these 23 fragments as
      probes, showed that copia-like retrotransposons were present in moderate to high
      copy numbers in all the rice genome although the exact copy number cannot be
      determined. The major difference revealed by southern analysis is a
      differentiation between the four indica varieties as one group and the four
      japonica varieties and the two wild rice accessions as another group.
      Polymorphisms were also detected among the indica and japonica varieties by major
      bands and repeatable minor bands. Five hybridization bands were mapped to
      chromosomes 3, 4, 8, and 9, respectively. All the five bands were inherited in a
      dominant Mendelian fashion and were not allelic with each other, indicating that
      the same element did not reside on the same location in different rice
      accessions. No transcript of the copia-like reverse transcriptase was detected on
      northern blot. The results suggest that the sequence heterogeneity and
      distributional variability of retrotransposons may be one of contributory factors
      causing genetic diversity in rice.

PMID- 9154987
TI  - Mutagenesis of the D-E loop of photosystem II reaction centre protein D1.
      Function and assembly of photosystem II.
AB  - The sequence connecting alpha-helices D and E of the D1 protein in photosystem II
      (PSII) is longer than that found in the corresponding loop of the L subunit in
      the rhodobacterial reaction centre. This sequence was mutated in order to
      determine its role in oxygenic photosynthesis. Site-specific mutants, including
      point mutations and deletions of different size, of the PEST-like region and the
      putative cleavage area in the D-E loop of the D protein were constructed in
      Synechocystis sp. PCC 6803. The effects of mutations on the functional and
      structural properties of PSII and turnover of the D1 protein were examined. Our
      results demonstrate that deletion of either the PEST-like sequence (deltaR225
      F239) or the putative cleavage region (deltaG240-V249, deltaR225-V249) of the D1
      protein resulted in severe perturbations on the function of the QB electron
      acceptor of PSII. However, PSII centres of the mutant with deleted PEST region
      remained functional enough to support autotrophic growth whereas deletions of the
      putative cleavage region prevented autotrophic growth. Although enhanced
      degradation rates of the mutant D1 proteins under low-light growth conditions
      demonstrate that neither the PEST-like sequence nor the putative cleavage region
      are required for D1 proteolysis, it became clear that the extension in the D-E
      loop of the D1 protein is essential for proper PSII assembly and photoautotrophic
      growth. Moreover, modifications of the D-E loop resulted in transcriptional
      activation of the psbA gene, indicating that neither light intensity, as such,
      nor the activity of the electron transfer chain are the only determinants in
      regulation of psbA gene transcription.

PMID- 9154988
TI  - Isolation and transcript analysis of gibberellin 20-oxidase genes in pea and bean
      in relation to fruit development.
AB  - PCR was used with degenerate primers based on conserved amino acid sequences in
      gibberellin (GA) 20-oxidases to isolate cDNA clones for these enzymes from young
      seeds of pea (Pisum sativum) and developing embryos of French bean (Phaseolus
      vulgaris). One GA 20-oxidase cDNA (Ps27-12) was obtained from pea and three (Pv
      15-11, Pv73-1 and Pv85-26) from bean. Their identities were confirmed by
      demonstrating that fusion proteins expressed in Escherichia coli exhibited GA 20
      oxidase activity, converting [14C]GA12 to [14C]GA9. The intermediates in this
      three-step reaction, GA15 and GA24, were also identified as products. The
      expression proteins from three of the clones (Ps27-12, Pv15-11 and Pv73-1) were
      also shown to convert GA53 to GA20, as effectively as they did GA12. On the basis
      of transcript levels measured by northern blot analysis, the pea GA 20-oxidase
      gene is most highly expressed in young leaves, fully expanded internodes, very
      young seeds (until 4 days after anthesis) and expanding pods (from 3 days after
      anthesis at least until day 6). Expression in pods from 3-day-old unpollinated
      ovaries is higher than in those from pollinated ovaries. Treatment of
      unpollinated ovaries with GA3 to induce parthenocarpic fruit-set severely reduced
      the amount of GA 20-oxidase mRNA, whereas treatment with 2,4-D, although inducing
      fruit-set, did not reduce the levels of these transcripts. Plant decapitation
      above an unpollinated ovary resulted in very high levels of GA 20-oxidase mRNA in
      the pod. The three GA 20-oxidase genes from French bean showed very different
      patterns of expression: Pv 15-1 was expressed in the roots, young leaves, and
      developing seeds, but most highly in immature cotyledons, while Pv73-1 has a
      similar expression pattern to Ps27-12, with transcripts found only in young seeds
      and young leaves, where it was particularly abundant. Transcripts corresponding
      to Pv85-26 were detected in developing seeds, and just traces in the young
      leaves. Southern blot analysis indicated that the bean GA 20-oxidases are each
      encoded by single-copy genes, whereas one more gene, homologous to Ps27-12, could
      also exist in pea.

PMID- 9154989
TI  - Cloning and characterization of the OsNramp family from Oryza sativa, a new
      family of membrane proteins possibly implicated in the transport of metal ions.
AB  - The mammalian Nramp1 protein is an integral membrane protein expressed
      exclusively in macrophages, where it plays a critical role in the ability of
      these cells to destroy ingested microbes. The bactericidal mechanism of action of
      Nramp1 remains unknown. We report the identification and characterization of cDNA
      clones corresponding to three homologues of the mammalian Nramp1 gene from the
      genome of Oryza sativa, OsNramp1, OsNramp2, and OsNramp3. These three genes
      encode a novel group of highly similar hydrophobic polypeptides sharing between
      64% and 75% sequence similarity, that show similar hydropathy profiles, and
      predicted secondary structure, including the same number, position, and sequence
      characteristics (including conserved charges) of transmembrane domains. Together,
      these define a highly conserved membrane associated hydrophobic core. The three
      plant proteins show a remarkable degree of sequence similarity with their
      mammalian counterpart (60% to 70% similarity), including primary and secondary
      structure elements previously described in ion transporters and channels.
      Expression studies in normal plant tissues indicate that while OsNramp1 is
      expressed primarily in roots, and OsNramp2 is primarily expressed in leaves,
      OsNramp3 is expressed in both tissues. The recent discovery that the yeast Nramp
      homologue SMF1 functions as a manganese transporter raises the exciting
      possibility that OsNramp encodes a family of metal ion transporters in plants.

PMID- 9154991
TI  - Excision of the maize transposable element Ac in periclinal chimeric leaves of
      35S-Ac-rolC transgenic aspen-Populus.
AB  - The transposable element Ac from maize, in combination with the phenotypic
      selectable marker rolC, was employed in transformation experiments of a hybrid
      aspen clone. A number of transgenic clones exhibited light-green sectors on green
      leaves. In vitro regeneration from leaves showing a high number of light-green
      spots resulted in R2 plants, which also showed light-green sectored leaves.
      However, only one out of 385 regenerated plants obtained showed green leaves.
      Both PCR and northern analysis indicated Ac excision and restoration of rolC
      expression. In Southern blot analysis of this green plant additional bands were
      observed as compared to the original R1 plant. The occurrence of these bands and
      a suggested Ac excision in the non-green L1-epidermal layer leading to periclinal
      chimerism of this plant is discussed.

PMID- 9154990
TI  - Identification and characterization of (GA/CT)n-microsatellite loci from Quercus
      petraea.
AB  - In this study a size selected genomic library from Quercus petraea was screened
      for (GA/CT)n-microsatellite sequences. The resulting loci were analysed by PCR
      for their usefulness as molecular markers in Q. petraea and Q. robur. 17 out of
      52 tested primer pairs resulted in the amplification of a polymorphic single
      locus pattern. The number of alleles found per locus varied from 6 to 16.
      Combining the genetic variation observed for the characterized loci provides a
      unique genotype for all the individuals tested. Using intraspecific controlled
      crosses of Q. robur trees Mendelian inheritance could be shown for five loci.

PMID- 9154993
TI  - Peroxynitrite: a two-faced metabolite of nitric oxide.
AB  - The discovery that nitric oxide (NO) reacts with superoxide (O2.-) forming
      peroxynitrite (ONOO-) (1) and the proof that this reaction occurs in vivo (2,3)
      holds enormous implications for the understanding of free radicals in biological
      systems. Not only in mammalian defense mechanisms against microorganisms, but
      also in pathophysiology during overexposure of tissues to radicals or other
      highly reactive species. Peroxynitrite is a highly reactive compound with harmful
      effects on cells and could therefore be an important microbicidal compound.
      Furthermore, the reaction of superoxide with NO interferes with NO signalling
      mechanisms. NO is not only released in response to inflammatory agents by
      inflammatory cells, but is also an important messenger molecule in paracrine
      mechanisms and neurotransmission. Whether peroxynitrite formation is a negative
      side effect of NO and superoxide release, or a functional characteristic is yet
      to be determined, and will be discussed in this review.

PMID- 9154992
TI  - Characterization of a structurally and functionally diverged acyl-acyl carrier
      protein desaturase from milkweed seed.
AB  - A cDNA for a structurally variant acyl-acyl carrier protein (ACP) desaturase was
      isolated from milkweed (Asclepias syriaca) seed, a tissue enriched in palmitoleic
      (16:1delta9)* and cis-vaccenic (18:1delta11) acids. Extracts of Escherichia coli
      that express the milkweed cDNA catalyzed delta9 desaturation of acyl-ACP
      substrates, and the recombinant enzyme exhibited seven- to ten-fold greater
      specificity for palmitoyl (16:0)-ACP and 30-fold greater specificity for
      myristoyl (14:0)-ACP than did known delta9-stearoyl (18:0)-ACP desaturases. Like
      other variant acyl-ACP desaturases reported to date, the milkweed enzyme contains
      fewer amino acids near its N-terminus compared to previously characterized delta9
      18:0-ACP desaturases. Based on the activity of an N-terminal deletion mutant of a
      delta9-18:0-ACP desaturase, this structural feature likely does not account for
      differences in substrate specificities.

PMID- 9154995
TI  - Effects of angiotensin-II infusion at pressor and subpressor doses on endothelin
      1 plasma levels in healthy men.
AB  - Several lines of evidence suggest that effects of angiotensin-II (A-II) could be
      mediated in part by endothelin-1 (ET-1): A-II enhances production and secretion
      of ET-1 which in turn may contribute to the pressor effects and mitogenic actions
      of A-II. We have conducted a randomized controlled cross-over study to
      investigate whether A-II increases ET-1 plasma levels in humans at pressor doses.
      Each of the eight healthy male volunteers received a subpressor and pressor dose
      of A-II which were assessed by titration of the individual dose dependent blood
      pressure responses to A-II-infusion. The mean subpressor dose of A-II was 0.62
      ng/kg/min. (range: 0.31-1.25); the mean pressor dose of A-II was 8.44 ng/kg/min.
      (range 2.5-20), yielding an average increase in mean arterial pressure by 35%
      (95% confidence interval [CI]: 24-45%). Plasma ET-1 concentrations increased
      significantly only in response to pressor doses of A-II (Friedman ANOVA p=0.022):
      ET-1 increased by 89 % (CI: 24-154%) over baseline (1.7 pmol/L; CI: 1.4-2.0) 60
      min. after starting the pressor infusion of A-II and remained elevated throughout
      the 4-hours observation period. In conclusion, A-II at pressor doses but not at
      subpressor doses induced an increase in plasma levels of ET- 1 in healthy
      subjects. This finding may be of relevance for various diseases associated with
      increased production of A-II and could potentially have therapeutic implications.

PMID- 9154994
TI  - Diabetic neuropathy in sucrose-fed Otsuka Long-Evans Tokushima fatty rats: effect
      of an aldose reductase inhibitor, TAT.
AB  - In an animal model of human non-insulin dependent diabetes mellitus (NIDDM),
      Otsuka Long-Evans Tokushima Fatty (OLETF) rats were fed with sucrose for 8 weeks
      to obtain severe hyperglycemia. The effects of sucrose administration on
      peripheral nerve functions, motor nerve conduction velocity (MNCV) and
      coefficient of variance of R-R interval (CVR-R), were investigated with
      concomitant measuring of sciatic nerve blood flow (SNBF), ADP-induced platelet
      aggregation and polyol content in the sciatic nerves. The effects of an aldose
      reductase inhibitor, TAT, on these parameters were also studied. Administration
      of sucrose to OLETF rats caused significant body weight reduction and remarkable
      hyperglycemia. Sucrose-fed OLETF rats demonstrated significantly delayed MNCV,
      decreased CVR-R, reduced SNBF and increased platelet aggregation activity to ADP.
      Sorbitol and fructose accumulation, and myo-inositol depletion in sciatic nerves
      were observed only in sucrose-fed OLETF rats. These abnormalities were all
      ameliorated by the treatment with TAT. These observations suggest that the
      sucrose-fed OLETF rat is a useful animal model for studying the pathogenesis of
      diabetic neuropathy in human NIDDM, and that an aldose reductase inhibitor is a
      useful therapeutic agent for the treatment of diabetic neuropathy.

PMID- 9154996
TI  - Kinetic parameters of Thymidine kinase and DNA synthesis during liver
      regeneration: role of thyroid hormones.
AB  - The role of thyroid hormones in DNA synthesis and in the activity of Thymidine
      kinase (TK), a key regulatory enzyme of DNA synthesis was studied in
      proliferating hepatocytes in vivo. Liver regeneration after partial hepatectomy
      was used as a model for controlled cell division in rats having different thyroid
      status - euthyroid, hypothyroid and 3,3',5'-triiodo-L-thyronine (T3)-treated
      hypothyroid. Partial hepatectomy caused a significant elevation of DNA synthesis
      (p<0.01) in all the three groups compared to their sham-operated counterparts.
      Hypothyroid hepatectomised animals showed significantly lower (p<0.01) level of
      DNA synthesis than euthyroid hepatectomised animals. A single subcutaneous dose
      of T3 to hypothyroid sham-operated animals resulted in a significant increase
      (p<0.01) of DNA synthesis in the intact liver. This was comparable to the level
      of DNA synthesis occurring in regenerating liver of euthyroid animals. In
      hypothyroid hepatectomised animals, T3 showed an additive effect on DNA synthesis
      and this group exhibited maximum level of DNA synthesis (p<0.01). Studies of the
      kinetic parameters of TK show that the Michelis-Menten constant, (K(m)) of TK for
      thymidine was altered by the thyroid status. K(m) increased significantly
      (p<0.01) in untreated hypothyroid animals when compared to the euthyroid rats. T3
      treatment of hypothyroid animals reversed this effect and this group showed the
      lowest value for K(m) (p<0.01). Thus our results indicate that thyroid hormones
      can influence DNA synthesis during liver regeneration and they may regulate the
      activity of enzymes such as Thymidine kinase which are important for DNA
      synthesis and hence cell division.

PMID- 9154997
TI  - Participation of the nitric oxide pathway in cold-induced hypertension.
AB  - Several mechanisms are known to participate in cold-induced hypertension, but no
      information exist on the role of the nitric oxide (NO). In the present study, we
      assessed the participation of nitric oxide in cold-induced hypertension by means
      of inhibition of NO synthase. Experiments were performed in rats treated with N
      omega-nitro-L-arginine (L-NNA) injected i.p. at a dose of 25 mg/kg body weight
      twice a day for four consecutive days. Control animals received saline injections
      of the same volume. Two days before the experiment, the femoral artery was
      cannulated for blood pressure recording. Arterial blood pressure was measured at
      25 degrees C for 30 min (control period), followed by a 3.5 hour period at 4
      degrees C (cold exposure) and, eventually, a last 3 hour period after removal
      from cold (back to 25 degrees C). In control animals, at 25 degrees C, mean
      arterial blood pressure was 112.5+/-3.6 mmHg and heart rate was 380+/-3.5 bpm. L
      NNA treatment caused an increase in blood pressure to 155.0+/-3.5 mmHg (P<0.01)
      and in heart rate to 410+/-6.0 bpm (P<0.05). Exposure to cold caused blood
      pressure to increase up to 131.5+/-3.6 mmHg (P<0.05) in the control group,
      whereas no significant change could be measured in treated animals. Recovery from
      cold exposure led to a decrease in blood pressure in control animals, but not in
      treated animals. These results indicate that NO plays a role in the development
      of cold-induced elevation of blood pressure.

PMID- 9154998
TI  - The first attempt at radioisotopic evaluation of the integrity of the nose-brain
      barrier.
AB  - The first attempt at radioisotopic assessment of the integrity of the nose-brain
      barrier was performed on an anosmic patient by spraying an aliquot of a mixture
      of 99mTc-DTPA and hyaluronidase onto the olfactory mucosa with the patient's head
      positioned vertically and subsequently measuring the cerebral radioactivity. A
      significant rise in cerebral radioactivity was observed 5 minutes after
      introduction of the radioisotope. This simple technique will aid in assessing
      olfactory impairment from selected etiologies and also in testing the integrity
      of the nose-brain barrier. In view of the study of diseases such as viral
      encephalitis and Alzheimer's disease, the clinical implications of this method
      cannot be overemphasized. This principle may also facilitate developing novel
      pharmaceuticals for some brain diseases.

PMID- 9154999
TI  - Melatonin induces membrane conductance changes in isolated retinal rod receptor
      cells.
AB  - Experiments were conducted to verify whether the neurohormone melatonin
      influences the membrane conductance of photoreceptors isolated from the frog
      retina. It has been found that 20 microM melatonin decreases membrane
      conductances both in the linear and non linear ranges by <0.4 nS. These actions
      are estimated to produce in dark adapted photoreceptors an increase of the
      response to a dim light induced change of the dark current of about 21%, i.e.
      from 1.3 to 1.62 mV/pA.

PMID- 9155000
TI  - Effect of cadmium on purified hepatic flavokinase: involvement of reactive -SH
      group(s) in the inactivation of flavokinase by cadmium.
AB  - The effect of cadmium (Cd2+) was studied in vitro on the flavokinase (ATP :
      riboflavin 5'-phosphotransferase, EC 2.7.1.26) activity purified from rat liver.
      Cadmium inhibited flavokinase activity in a concentration-dependent manner and
      the effect was completely reversed by increasing concentration of zinc (Zn2+),
      indicating a competition between Zn2+ and Cd2+ for binding with the enzyme.
      Further, a competition between riboflavin and Cd2+ hints at the possibility that
      Zn2+ and Cd2+ probably compete for the same site on the enzyme where riboflavin
      binds. Our studies further reveal that hepatic flavokinase contains essential,
      accessible and functional thiol group(s) as evidenced by a concentration
      dependent inhibition by sulfhydryl reagents and protection by thiol protectors
      like glutathione or dithiothreitol. Furthermore, the enzyme could also be
      protected from the inhibitory effect of Cd2+ and Hg2+ by glutathione and
      dithiothreitol suggesting that Cd2+ probably interacts with reactive thiol group
      at or near the active site of the enzyme to cause inhibition.

PMID- 9155001
TI  - Cholinergic-induced production of reactive oxygen species in human neuroblastoma
      cells.
AB  - Stimulation of human SH-SY5Y neuroblastoma cells by a muscarinic receptor
      agonist, carbachol (CCh; 1 mM), elevated levels of free intracellular calcium and
      subsequently increased the production of reactive oxygen species (ROS).
      Quinuclidinylbenzilate (QNB) binding increased at 1 h after CCh, but returned
      back to the control level at 3 h. Production of ROS increased, however, during
      the 3 h time period. CCh also increased the translocation of protein kinase C
      (PKC) to the membrane. ROS production was completely blocked by atropine and a
      PKC inhibitor, Ro 31-8220. These results show that increased ROS production was a
      result of muscarinic receptor stimulation, and that PKC had an active role in
      this cellular stimulation. ROS production upon cellular stimulation by CCh was
      completely inhibited also by superoxide dismutase, and partially by catalase,
      indicating that the formation of superoxide anion dominated in cholinergic
      induced generation of ROS in human neuroblastoma cells. These results also show
      that muscarinic stimulation causes sustained ROS production in human
      neuroblastoma cells. The slow increase in ROS production by CCh suggest a
      stepwise cascade of events leading to oxidative stress with a triggering role of
      cholinergic muscarinic receptors in this process.

PMID- 9155002
TI  - Saturating concentration for the uptake of free fatty acids and release of ketone
      bodies in vivo in rat liver.
AB  - The aim of this study is to determine how hepatic uptake of free fatty acids
      (FFA) and release of ketone bodies (KB) in vivo are influenced by plasma
      concentration of FFA. Anesthetized fasted rats were cannulated (aorta, portal
      vein, hepatic vein and inferior vena cava) and were intravenously injected with
      heparin (1000 U x kg(-1) body weight) or infused with lipid emulsions at rates of
      0, 0.39 and 0.77 mg TG x min(-1) x rat(-1). Heparin injection elevated systemic
      concentration of plasma FFA significantly to 1.0 mM from 0.7 mM in the saline
      injected rats. The arteriovenous (AV) gradient of FFA across the liver in the
      heparin-injected rats was, however, unchanged from the saline-injected rats.
      Hepatic release of KB in the heparin-injected rats, as indicated by the negative
      gradient across the liver, was found to be 83 % greater than the saline-injected
      rats. In the rats infused with lipid emulsions, plasma FFA concentrations were
      found to elevate further to 2.2 mM. However, no further increases in hepatic
      uptake of FFA and release of KB were found. Hepatic gradients of FFA and KB in
      the rats infused with lipid emulsions and injected with heparin were found to be
      the same. It may be concluded, therefore, that the uptake of FFA and release of
      KB in vivo in rat livers may be saturated at a plasma FFA concentration <1.0 mM,
      much lower than reported previously in in vitro studies.

PMID- 9155004
TI  - Peripheral noxious stimulation releases spinal PGE2 during the first phase in the
      formalin assay of the rat.
AB  - Injection of formalin (5%; 50 microl) into the dorsal surface of the hind paw of
      rats evoked a characteristic biphasic flinching behaviour of the injured paw
      accompanied by a significant increase in the interstitial prostaglandin E2 (PGE2)
      concentration of the dorsal lumbar spinal cord. Interestingly, the increase in
      PGE2 concentration was only observed during the first phase of the formalin
      behavioural response (during the 0-10 and 10-20 min microdialysis-sample). Saline
      paw injection did not have a significant effect on behaviour or on PGE2
      concentration. These data suggest that spinal release of PGE2 is involved in
      nociceptive processing in the formalin-induced hyperalgesia model of the rat
      during the first but not second phase.

PMID- 9155003
TI  - In vitro influence of sublethal hypoxia on differentiation of the 3T3-L1
      preadipose cell line and its physiological implications.
AB  - Exposure of cultures of 3T3-L1 preadipose cells to nitrogen for 16 hours kills
      almost all of the cells, but after exposure to 5% oxygen for 16 hours most of the
      cells survive, and recover when culture is continued in 20% oxygen. The extent of
      recovery depends on the insulin concentration of the medium. Isotope
      incorporation and flow cytometry experiments show that exposure to 5% oxygen for
      16 hours growth arrests the cells and leads to an elongation of the G1-phase of
      the cell cycle. When 3T3-L1 cells are growth arrested in the presence of 5%
      oxygen and allowed to recover in the presence of 5 microg/ml insulin under 20%
      oxygen, they can be induced to differentiate by treatment with carbacyclin during
      the period of growth arrest. Activity of the marker enzyme glycerol-3-phosphate
      dehydrogenase increases from 46.5+/-17 mU/mg protein to 1506+/-271 mU/mg protein.
      The extent of differentiation is exponentially related to the concentration of
      carbacyclin in the medium.

PMID- 9155005
TI  - Antioxidant activity of metallothionein compared with reduced glutathione.
AB  - The antioxidant activity of metallothionein (MT) was investigated.
      Metallothionein scavenged hydroxyl radicals (HO.) to protect DNA from the
      oxidative attack by microsomes. This scavenging activity of MT was approximately
      50 times greater than reduced glutathione (GSH) on a molar basis. However, MT did
      not inhibit DNA damage induced by microsomes in the presence of adriamycin (ADM)
      Fe3+. Presumably, MT did not access DNA at the binding site of ADM-Fe3+ by steric
      hindrance. The MT also inhibited microsomal lipid peroxidation induced by ADP
      Fe3+ and NADPH. The inhibitory activity of MT was about 10 times greater than GSH
      on a molar basis. In addition, MT effectively inhibited the degradation of R
      phycoerythrin fluorescence induced by 2,2'-azobis-(2-amidino-propane)
      dihydrochloride, suggesting that MT scavenges peroxyl radicals. This activity of
      MT was approximately 100 times greater than GSH on a molar basis. Presumably, the
      inhibitory activity of MT against lipid peroxidation is due to its ability to
      scavenge lipid peroxyl radicals on the membrane surface. The antioxidant activity
      of MT seems to be due to MT scavenging free HO. and peroxyl radicals.

PMID- 9155006
TI  - Extracellular Ca2+-dependent contractile action of phorbol 12,13-dibutyrate on
      gall bladder from guinea pig.
AB  - The effects of phorbol 12,13 dibutyrate (PDBu) on the isometric tone of gall
      bladder strips isolated from guinea pig were investigated. PDBu caused the
      development of a contractile force at concentrations of 5 nM to 1 microM, which
      was abolished by staurosporine (30 nM). The contraction was completely inhibited
      in Ca2+-free solution and by pretreatment with verapamil (1 microM) or nifedipine
      (1 microM). A lower concentration of PDBu (1 nM) potentiated the contractile
      response to KCl: it increased the sensitivity, but not the reactivity of KCl
      induced contraction. Ca2+-induced contraction in the solution with 15 mM KCl was
      significantly augmented by the pretreatment with 1 nM PDBu. However, PDBu (1 nM)
      affected neither Ca2+-induced contraction in the presence of Ca2+ ionophore
      A23187 (0.7 microM) and verapamil (1 microM) nor Ba2+-induced contraction in the
      Ca2+-free solution. These results suggest that activation of protein kinase C
      induces completely extracellular Ca2+-dependent contraction by activating the
      voltage-dependent Ca2+ channels in gall bladder of guinea pig.

PMID- 9155007
TI  - Essential role for gamma-tubulin in the acentriolar female meiotic spindle of
      Drosophila.
AB  - Microtubule nucleation in vivo requires gamma-tubulin, a highly conserved
      component of microtubule-organizing centers. In Drosophila melanogaster there are
      two gamma-tubulin genes, gammaTUB23C and gammaTUB37C. Here we report the
      cytological and molecular characterization of the 37C isoform. By Western
      blotting, this protein can only be detected in ovaries and embryos. Antibodies
      against this isoform predominantly label the centrosomes in embryos from early
      cleavage divisions until cycle 15, but fail to reveal any particular localization
      of gamma-tubulin in the developing egg chambers. The loss of function of this
      gene results in female sterility and has no effect on viability or male
      fertility. Early stages of oogenesis are unaffected by mutations in this gene, as
      judged both by morphological criteria and by localization of reporter genes, but
      the female meiotic spindle is extremely disrupted. Nuclear proliferation within
      the eggs laid by mutant females is also impaired. We conclude that the expression
      of the 37C gamma-tubulin isoform of D. melanogaster is under strict developmental
      regulation and that the organization of the female meiotic spindle requires gamma
      tubulin.

PMID- 9155008
TI  - Endosomal transport function in yeast requires a novel AAA-type ATPase, Vps4p.
AB  - In a late-Golgi compartment of the yeast Saccharomyces cerevisiae, vacuolar
      proteins such as carboxypeptidase Y (CPY) are actively sorted away from the
      secretory pathway and transported to the vacuole via a pre-vacuolar, endosome
      like intermediate. The vacuolar protein sorting (vps) mutant vps4 accumulates
      vacuolar, endocytic and late-Golgi markers in an aberrant multilamellar pre
      vacuolar compartment. The VPS4 gene has been cloned and found to encode a 48 kDa
      protein which belongs to the protein family of AAA-type ATPases. The Vps4 protein
      was purified and shown to exhibit an N-ethylmaleimide-sensitive ATPase activity.
      A single amino acid change within the AAA motif of Vps4p yielded a protein that
      lacked ATPase activity and did not complement the protein sorting or
      morphological defects of the vps4 delta1 mutant. Indeed, when expressed at normal
      levels in wild-type cells, the mutant vps4 gene acted as a dominant-negative
      allele. The phenotypic characterization of a temperature-sensitive vps4 allele
      showed that the immediate consequence of loss of Vps4p function is a defect in
      vacuolar protein delivery. In this mutant, precursor CPY was not secreted but
      instead accumulated in an intracellular compartment, presumably the pre-vacuolar
      endosome. Electron microscopy revealed that upon temperature shift, exaggerated
      stacks of curved cisternal membranes (aberrant endosome) also accumulated in the
      vps4ts mutant. Based on these and other observations, we propose that Vps4p
      function is required for efficient transport out of the pre-vacuolar endosome.

PMID- 9155009
TI  - Transmembrane domain-dependent sorting of proteins to the ER and plasma membrane
      in yeast.
AB  - Sorting of membrane proteins between compartments of the secretory pathway is
      mediated in part by their transmembrane domains (TMDs). In animal cells, TMD
      length is a major factor in Golgi retention. In yeast, the role of TMD signals is
      less clear; it has been proposed that membrane proteins travel by default to the
      vacuole, and are prevented from doing so by cytoplasmic signals. We have
      investigated the targeting of the yeast endoplasmic reticulum (ER) t-SNARE Ufe1p.
      We show that the amino acid sequence of the Ufe1p TMD is important for both
      function and ER targeting, and that the requirements for each are distinct.
      Targeting is independent of Rer1p, the only candidate sorting receptor for TMD
      sequences currently known. Lengthening the Ufe1p TMD allows transport along the
      secretory pathway to the vacuole or plasma membrane. The choice between these
      destinations is determined by the length and composition of the TMD, but not by
      its precise sequence. A longer TMD is required to reach the plasma membrane in
      yeast than in animal cells, and shorter TMDs direct proteins to the vacuole. TMD
      based sorting is therefore a general feature of the yeast secretory pathway, but
      occurs by different mechanisms at different points.

PMID- 9155010
TI  - Sequential action of two hsp70 complexes during protein import into mitochondria.
AB  - The mitochondrial chaperone mhsp70 mediates protein transport across the inner
      membrane and protein folding in the matrix. These two reactions are effected by
      two different mhsp70 complexes. The ADP conformation of mhsp70 favors formation
      of a complex on the inner membrane; this 'import complex' contains mhsp70, its
      membrane anchor Tim44 and the nucleotide exchange factor mGrpE. The ATP
      conformation of mhsp70 favors formation of a complex in the matrix; this 'folding
      complex' contains mhsp70, the mitochondrial DnaJ homolog Mdj1 and mGrpE. A
      precursor protein entering the matrix interacts first with the import complex and
      then with the folding complex. A chaperone can thus function as part of two
      different complexes within the same organelle.

PMID- 9155011
TI  - Growth retardation and early death of beta-1,4-galactosyltransferase knockout
      mice with augmented proliferation and abnormal differentiation of epithelial
      cells.
AB  - Carbohydrate chains on a glycoprotein are important not only for protein
      conformation, transport and stability, but also for cell-cell and cell-matrix
      interactions. UDP-Gal:N-acetylglucosamine beta-1,4-galactosyltransferase (GalT)
      (EC 2.4.1.38) is the enzyme which transfers galactose (Gal) to the terminal N
      acetylglucosamine (GlcNAc) of complex-type N-glycans in the Golgi apparatus. In
      addition, it has also been suggested that this enzyme is involved directly in
      cell-cell interactions during fertilization and early embryogenesis through a
      subpopulation of this enzyme distributed on the cell surface. In this study, GalT
      deficient mice were produced by gene targeting in order to examine the
      pathological effects of the deficiency. GalT-deficient mice were born normally
      and were fertile, but they exhibited growth retardation and semi-lethality.
      Epithelial cell proliferation of the skin and small intestine was enhanced, and
      cell differentiation in intestinal villi was abnormal. These observations suggest
      that GalT plays critical roles in the regulation of proliferation and
      differentiation of epithelial cells after birth, although this enzyme is
      dispensable during embryonic development.

PMID- 9155012
TI  - Unrestrained nociceptive response and disregulation of hearing ability in mice
      lacking the nociceptin/orphaninFQ receptor.
AB  - In the G-protein-coupled receptor superfamily, the opioid receptor subfamily is
      constituted of the three distinct opioid receptors (namely delta-, mu- and kappa
      subtypes) and the receptor for nociceptin (also designated orphaninFQ). The
      members of the opioid receptor subfamily were known to mediate a variety of
      cellular inhibitory effects. The three opioid receptors are known to play central
      roles in mediating analgesia and many other physiological activities; however,
      the nociceptin receptor was identified recently and less is known about its
      physiological roles. Here we report the generation and characterization of mice
      lacking the nociceptin receptor. The knockout mice showed no significant
      differences in nociceptive threshold and locomotor activity compared with control
      mice, but they lost nociceptin-induced behavioral responses. These results
      indicate that the nociceptin system is not essential for regulation of
      nociception or locomotor activity. On the other hand, we found insufficient
      recovery of hearing ability from the adaptation to sound exposure in the mutant
      mice. Thus, the nociceptin system appears to participate in the regulation of the
      auditory system.

PMID- 9155013
TI  - Functional redundancy of the Nur77 and Nor-1 orphan steroid receptors in T-cell
      apoptosis.
AB  - The transcription factor Nur77 (NGFI-B), a member of the steroid nuclear receptor
      superfamily, is induced to a high level during T-cell receptor (TCR)-mediated
      apoptosis. A transgenic dominant-negative Nur77 protein can inhibit the apoptotic
      process accompanying negative selection in thymocytes, while constitutive
      expression of Nur77 leads to massive cell death. Nur77-deficient mice, however,
      have no phenotype, suggesting the possible existence of a protein with redundant
      function to Nur77. To explore this possibility, we have characterized the role of
      two Nur77 family members, Nurr1 and Nor-1, in TCR-induced apoptosis. We found
      that Nor-1 and Nurr1 can transactivate through the same DNA element as Nur77, and
      that their transactivation activities can be blocked by a Nur77 dominant-negative
      protein. In thymocytes, Nor-1 protein is induced to a very high level upon TCR
      stimulation and has similar kinetics to Nur77. In contrast, Nurr1 is undetectable
      in stimulated thymocytes. Furthermore, constitutive expression of Nor-1 in
      thymocytes leads to massive apoptosis and up-regulation of CD25, suggesting a
      functional redundancy between Nur77 and Nor-1 gene products. As in the case of
      our Nur77-FL mice, FasL is not detectable in the thymocytes of Nor-1 transgenic
      mice. Constitutive expression of Nur77 in gld/gld mice rescues the
      lymphoproliferative phenotype of the FasL mutant mice. Thus, Nor-1 and Nur77
      demonstrate functional redundancy in an apparently Fas-independent apoptosis.

PMID- 9155014
TI  - Structural basis for the recognition of regulatory subunits by the catalytic
      subunit of protein phosphatase 1.
AB  - The diverse forms of protein phosphatase 1 in vivo result from the association of
      its catalytic subunit (PP1c) with different regulatory subunits, one of which is
      the G-subunit (G(M)) that targets PP1c to glycogen particles in muscle. Here we
      report the structure, at 3.0 A resolution, of PP1c in complex with a 13 residue
      peptide (G(M[63-75])) of G(M). The residues in G(M[63-75]) that interact with
      PP1c are those in the Arg/Lys-Val/Ile-Xaa-Phe motif that is present in almost
      every other identified mammalian PP1-binding subunit. Disrupting this motif in
      the G(M[63-75]) peptide and the M(110[1-38]) peptide (which mimics the
      myofibrillar targeting M110 subunit in stimulating the dephosphorylation of
      myosin) prevents these peptides from interacting with PP1. A short peptide from
      the PP1-binding protein p53BP2 that contains the RVXF motif also interacts with
      PP1c. These findings identify a recognition site on PP1c, invariant from yeast to
      humans, for a critical structural motif on regulatory subunits. This explains why
      the binding of PP1 to its regulatory subunits is mutually exclusive, and suggests
      a novel approach for identifying the functions of PP1-binding proteins whose
      roles are unknown.

PMID- 9155015
TI  - MAP kinase- and Rho-dependent signals interact to regulate gene expression but
      not actin morphology in cardiac muscle cells.
AB  - Post-natal growth of cardiac muscle cells occurs by hypertrophy rather than
      division and is associated with changes in gene expression and muscle fiber
      morphology. We show here that the protein kinase MEKK1 can induce reporter gene
      expression from the atrial natriuretic factor (ANF) promoter, a genetic marker
      that is activated during in vivo hypertrophy. MEKK1 induced both stress-activated
      protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK)
      activity; however, while the SAPK cascade stimulated ANF expression, activation
      of the ERK cascade inhibited expression. C3 transferase, a specific inhibitor of
      the small GTPase Rho, also inhibited both MEKK- and phenylephrine-induced ANF
      expression, indicating an additional requirement for Rho-dependent signals.
      Microinjection or transfection of C3 transferase into the same cells did not
      disrupt actin muscle fiber morphology, indicating that Rho-dependent pathways do
      not regulate actin morphology in cardiac muscle cells. While active MEKK1 was a
      potent activator of hypertrophic gene expression, this kinase did not induce
      actin organization and prevented phenylephrine-induced organization. These data
      suggest that multiple signals control hypertrophic phenotypes. Positive and
      negative signals mediated by parallel MAP kinase cascades interact with Rho
      dependent pathways to regulate hypertrophic gene expression while other signals
      induce muscle fiber morphology in cardiac muscle cells.

PMID- 9155016
TI  - Interaction of MAP kinase with MAP kinase kinase: its possible role in the
      control of nucleocytoplasmic transport of MAP kinase.
AB  - The mitogen-activated protein kinase (MAPK) cascade consisting of MAPK and its
      direct activator, MAPK kinase (MAPKK), is essential for signaling of various
      extracellular stimuli to the nucleus. Upon stimulation, MAPK is translocated to
      the nucleus, whereas MAPKK stays in the cytoplasm. It has been shown recently
      that the cytoplasmic localization of MAPKK is determined by its nuclear export
      signal (NES) in the near N-terminal region (residues 33-44). However, the
      mechanism determining the subcellular distribution of MAPK has been poorly
      understood. Here, we show that introduction of v-Ras, active STE11 or
      constitutively active MAPKK can induce nuclear translocation of MAPK in mammalian
      cultured cells. Furthermore, we show evidence suggesting that MAPK is localized
      to the cytoplasm through its specific association with MAPKK and that nuclear
      accumulation of MAPK is accompanied by dissociation of a complex between MAPK and
      MAPKK following activation of the MAPK pathway. We have identified the MAPK
      binding site of MAPKK as its N-terminal residues 1-32. Moreover, a peptide
      encompassing the MAPK-binding site and the NES sequence of MAPKK has been shown
      to be sufficient to retain MAPK to the cytoplasm. These findings reveal the
      molecular basis regulating subcellular distribution of MAPK, and identify a novel
      function of MAPKK as a cytoplasmic anchoring protein for MAPK.

PMID- 9155017
TI  - Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and
      Mnk2.
AB  - Mitogen-activated protein (MAP) kinases bind tightly to many of their
      physiologically relevant substrates. We have identified a new subfamily of murine
      serine/threonine kinases, whose members, MAP kinase-interacting kinase 1 (Mnk1)
      and Mnk2, bind tightly to the growth factor-regulated MAP kinases, Erk1 and Erk2.
      MNK1, but not Mnk2, also binds strongly to the stress-activated kinase, p38. MNK1
      complexes more strongly with inactive than active Erk, implying that Mnk and Erk
      may dissociate after mitogen stimulation. Erk and p38 phosphorylate MNK1 and
      Mnk2, which stimulates their in vitro kinase activity toward a substrate,
      eukaryotic initiation factor-4E (eIF-4E). Initiation factor eIF-4E is a
      regulatory phosphoprotein whose phosphorylation is increased by insulin in an Erk
      dependent manner. In vitro, MNK1 rapidly phosphorylates eIF-4E at the
      physiologically relevant site, Ser209. In cells, Mnk1 is post-translationally
      modified and enzymatically activated in response to treatment with either peptide
      growth factors, phorbol esters, anisomycin or UV. Mitogen- and stress-mediated
      MNK1 activation is blocked by inhibitors of MAP kinase kinase 1 (Mkk1) and p38,
      demonstrating that Mnk1 is downstream of multiple MAP kinases. MNK1 may define a
      convergence point between the growth factor-activated and one of the stress
      activated protein kinase cascades and is a candidate to phosphorylate eIF-4E in
      cells.

PMID- 9155018
TI  - MNK1, a new MAP kinase-activated protein kinase, isolated by a novel expression
      screening method for identifying protein kinase substrates.
AB  - We have developed a novel expression screening method for identifying protein
      kinase substrates. In this method, a lambda phage cDNA expression library is
      screened by in situ, solid-phase phosphorylation using purified protein kinase
      and [gamma-32P]ATP. Screening a HeLa cDNA library with ERK1 MAP kinase yielded
      cDNAs of previously characterized ERK substrates, c-Myc and p90RSK, demonstrating
      the utility of this method for identifying physiological protein kinase
      substrates. A novel clone isolated in this screen, designated MNK1, encodes a
      protein-serine/threonine kinase, which is most similar to MAP kinase-activated
      protein kinase 2 (MAPKAP-K2), 3pK/MAPKAP-K3 and p90RSK. Bacterially expressed
      MNK1 was phosphorylated and activated in vitro by ERK1 and p38 MAP kinases but
      not by JNK/SAPK. Further, MNK1 was activated upon stimulation of HeLa cells with
      12-O-tetradecanoylphorbol-13-acetate, fetal calf serum, anisomycin, UV
      irradiation, tumor necrosis factor-alpha, interleukin-1beta, or osmotic shock,
      and the activation by these stimuli was differentially inhibited by the MEK
      inhibitor PD098059 or the p38 MAP kinase inhibitor SB202190. Together, these
      results indicate that MNK1 is a novel class of protein kinase that is activated
      through both the ERK and p38 MAP kinase signaling pathways.

PMID- 9155020
TI  - D-myo-inositol 1,4,5-trisphosphate 3-kinase A is activated by receptor activation
      through a calcium:calmodulin-dependent protein kinase II phosphorylation
      mechanism.
AB  - D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] 3-kinase, the enzyme
      responsible for production of D-myo-inositol 1,3,4,5-tetrakisphosphate, was
      activated 3- to 5-fold in homogenates of rat brain cortical slices after
      incubation with carbachol. The effect was reproduced in response to UTP in
      Chinese hamster ovary (CHO) cells overexpressing Ins(1,4,5)P3 3-kinase A, the
      major isoform present in rat and human neuronal cells. In ortho-32P-labelled
      cells, the phosphorylated 53 kDa enzyme could be identified after receptor
      activation by immunoprecipitation. The time course of phosphorylation was very
      similar to that observed for carbachol (or UTP)-induced enzyme activation. Enzyme
      phosphorylation was prevented in the presence of okadaic acid. Calmodulin (CaM)
      kinase II inhibitors (i.e. KN-93 and KN-62) prevented phosphorylation of
      Ins(1,4,5)P3 3-kinase. Identification of the phosphorylation site in transfected
      CHO cells indicated that the phosphorylated residue was Thr311. This residue of
      the human brain sequence lies in an active site peptide segment corresponding to
      a CaM kinase II-mediated phosphorylation consensus site, i.e. Arg-Ala-Val-Thr.
      The same residue in Ins(1,4,5)P3 3-kinase A was also phosphorylated in vitro by
      CaM kinase II. Phosphorylation resulted in 8- to 10-fold enzyme activation and a
      25-fold increase in sensitivity to the Ca2+:CaM complex. In this study, direct
      evidence is provided for a novel regulation mechanism for Ins(1,4,5)P3 3-kinase
      (isoform A) in vitro and in intact cells.

PMID- 9155019
TI  - G proteins in Ustilago maydis: transmission of multiple signals?
AB  - In the phytopathogenic fungus Ustilago maydis, cell fusion is governed by a
      pheromone signalling system. The pheromone receptors belong to the seven
      transmembrane class that are coupled to heterotrimeric G proteins. We have
      isolated four genes (gpa1 to gpa4) encoding alpha subunits of G proteins. Gpa1,
      Gpa2 and Gpa3 have homologues in other fungal species, while Gpa4 is novel. Null
      mutants in individual genes were viable and only disruption of gpa3 caused a
      discernible phenotype. gpa3 mutant strains were unable to respond to pheromone
      and thus were mating-deficient. A constitutively active allele of gpa3
      (gpa3(Q206L)) was generated by site-directed mutagenesis. Haploid strains
      harbouring gpa3(Q206L) were able to mate without pheromone stimulation,
      indicating that Gpa3 plays an active role in transmission of the pheromone
      signal. Surprisingly, Gpa3 is also required for pathogenic development, although
      pheromone signalling is not essential for this process.

PMID- 9155021
TI  - Mammalian Raf-1 is activated by mutations that restore Raf signaling in
      Drosophila.
AB  - An interaction with the Ras proto-oncogene product is a requirement for Raf-1
      activation in many signaling cascades. The significance of this interaction is
      demonstrated by the fact that a mutation preventing the Ras-Raf interaction
      severely impairs the function of both mammalian (Raf-1) and Drosophila (D-Raf)
      Raf proteins. In D-Raf, however, dominant intragenic mutations have been
      identified that suppress the effect of the Ras-binding site (RBS) mutation. To
      address the mechanism by which these mutations restore Raf signaling, we have
      introduced the suppressor mutations into the analogous residues of mammalian Raf
      1. Here, we show that rather than compensating for the RBS mutation by restoring
      the Ras-Raf-1 interaction, the suppressor mutations increase the enzymatic and
      biological activity of Raf-1, allowing Raf-1 to signal in the absence of Ras
      binding. Surprisingly, we find that while one of the suppressor mutations (P181L)
      increases the basal kinase activity of Raf-1, it also abolishes the ability of
      wild-type Raf-1 to become activated by Ras. This mutation occurs in the cysteine
      rich domain (CRD) of Raf-1 and demonstrates the importance of this region for a
      productive Ras-Raf interaction. Finally, we present evidence that the most
      activating suppressor mutation (G498S) increases Raf-1 activity by introducing a
      novel phosphorylation site into the L12 activation loop of the Raf-1 kinase
      domain.

PMID- 9155022
TI  - The heat shock protein 83 (Hsp83) is required for Raf-mediated signalling in
      Drosophila.
AB  - The heat shock protein Hsp90 has been shown to associate with various cellular
      signalling proteins such as steroid hormone receptors, src-like kinases and the
      serine/threonine kinase Raf. While the interaction between steroid hormone
      receptors and Hsp90 appears to be essential for ligand binding and activation of
      the receptors, the role of Hsp90 in Raf activation is less clear. We have
      identified mutations in the hsp83 gene, the Drosophila homologue of hsp90, in a
      search for dominant mutations that attenuate signalling from Raf in the
      developing eye. The mutations result in single amino acid substitutions in the
      Hsp83 protein and cause a dominant-negative effect on the function of the wild
      type protein. We show that both wild-type and mutant forms of Hsp83 bind to the
      activated Drosophila Raf but the mutant Hsp83 protein causes a reduction in the
      kinase activity of Raf. Our results indicate that Hsp83 is essential for Raf
      function in vivo.

PMID- 9155023
TI  - Positive and negative regulation of type II TGF-beta receptor signal transduction
      by autophosphorylation on multiple serine residues.
AB  - The type II transforming growth factor-beta (TGF-beta) receptor Ser/Thr kinase
      (TbetaRII) is responsible for the initiation of multiple TGF-beta signaling
      pathways, and loss of its function is associated with many types of human cancer.
      Here we show that TbetaRII kinase is regulated intricately by autophosphorylation
      on at least three serine residues. Ser213, in the membrane-proximal segment
      outside the kinase domain, undergoes intra-molecular autophosphorylation which is
      essential for the activation of TbetaRII kinase activity, activation of TbetaRI
      and TGF-beta-induced growth inhibition. In contrast, phosphorylation of Ser409
      and Ser416, located in a segment corresponding to the substrate recognition T
      loop region in a three-dimensional structural model of protein kinases, is
      enhanced by receptor dimerization and can occur via an intermolecular mechanism.
      Phosphorylation of Ser409 is essential for TbetaRII kinase signaling, while
      phosphorylation of Ser416 inhibits receptor function. Mutation of Ser416 to
      alanine results in a hyperactive receptor that is better able than wild-type to
      induce TbetaRI activation and subsequent cell cycle arrest. Since on a single
      receptor either Ser409 or Ser416, but not both simultaneously, can become
      autophosphorylated, our results show that TbetaRII phosphorylation is regulated
      intricately and affects TGF-beta receptor signal transduction both positively and
      negatively.

PMID- 9155024
TI  - Efg1p, an essential regulator of morphogenesis of the human pathogen Candida
      albicans, is a member of a conserved class of bHLH proteins regulating
      morphogenetic processes in fungi.
AB  - We identified a gene of the fungal pathogen Candida albicans, designated EFG1,
      whose high-level expression stimulates pseudohyphal morphogenesis in the yeast
      Saccharomyces cerevisiae. In a central region the deduced Efg1 protein is highly
      homologous to the StuA and Phd1/Sok2 proteins that regulate morphogenesis of
      Aspergillus nidulans and S. cerevisiae, respectively. The core of the conserved
      region is homologous to the basic helix-loop-helix (bHLH) motif of eukaryotic
      transcription factors, specifically to the human Myc and Max proteins. Fungal
      specific residues in the bHLH domain include the substitution of an invariant
      glutamate, responsible for target (E-box) specificity, by a threonine residue.
      During hyphal induction EFG1 transcript levels decline to low levels;
      downregulation is effected at the level of transcriptional initiation as shown by
      a EFG1 promoter-LAC4 fusion. A strain carrying one disrupted EFG1 allele and one
      EFG1 allele under the control of the glucose-repressible PCK1 promoter forms rod
      like, pseudohyphal cells, but is unable to form true hyphae on glucose-containing
      media. Overexpression of EFG1 in C. albicans leads to enhanced filamentous growth
      in the form of extended pseudohyphae in liquid and on solid media. The results
      suggest that Efg1p has a dual role as a transcriptional activator and repressor,
      whose balanced activity is essential for yeast, pseudohyphal and hyphal
      morphogenesis of C. albicans. Functional analogies between Efg1p and Myc are
      discussed.

PMID- 9155025
TI  - The activation domain of the MotA transcription factor from bacteriophage T4.
AB  - Bacteriophage T4 encodes a transcription factor, MotA, that binds to the -30
      region of middle-mode promoters and activates transcription by host RNA
      polymerase. We have solved the structure of the MotA activation domain to 2.2 A
      by X-ray crystallography, and have also determined its secondary structure by
      NMR. An area on the surface of the protein has a distinctive patch that is
      populated with acidic and hydrophobic residues. Mutations within this patch cause
      a defective T4 growth phenotype, arguing that the patch is important for MotA
      function. One of the mutant MotA activation domains was purified and analyzed by
      NMR, and the spectra clearly show that the domain is properly folded. The mutant
      full-length protein appears to bind DNA normally but is deficient in
      transcriptional activation. We conclude that the acidic/hydrophobic surface patch
      is specifically involved in transcriptional activation, which is reminiscent of
      eukaryotic acidic activation domains.

PMID- 9155026
TI  - Aiolos, a lymphoid restricted transcription factor that interacts with Ikaros to
      regulate lymphocyte differentiation.
AB  - Development of the lymphoid system is dependent on the activity of zinc finger
      transcription factors encoded by the Ikaros gene. Differences between the
      phenotypes resulting from a dominant-negative and a null mutation in this gene
      suggest that Ikaros proteins act in concert with another factor with which they
      form heterodimers. Here we report the cloning of Aiolos, a gene which encodes an
      Ikaros homologue that heterodimerizes with Ikaros proteins. In contrast to Ikaros
      -which is expressed from the pluripotent stem cell to the mature lymphocyte-
      Aiolos is first detected in more committed progenitors with a lymphoid potential
      and is strongly up-regulated as these differentiate into pre-T and pre-B cell
      precursors. The expression patterns of Aiolos and Ikaros, the relative
      transcriptional activity of their homo- and heteromeric complexes, and the
      dominant interfering effect of mutant Ikaros isoforms on Aiolos activity all
      strongly suggest that Aiolos acts in concert with Ikaros during lymphocyte
      development. We therefore propose that increasing levels of Ikaros and Aiolos
      homo- and heteromeric complexes in differentiating lymphocytes are essential for
      normal progression to a mature and immunocompetent state.

PMID- 9155028
TI  - The Adh-related gene of Drosophila melanogaster is expressed as a functional
      dicistronic messenger RNA: multigenic transcription in higher organisms.
AB  - Essentially all eukaryotic cellular mRNAs are monocistronic, and are usually
      transcribed individually. Two tandemly arranged Drosophila genes, alcohol
      dehydrogenase (Adh) and Adh-related (Adhr), are transcribed as a dicistronic
      transcript. From transcripts initiated from the Adh promoter, two classes of mRNA
      are accumulated, one is monocistronic and encodes Adh alone, the other is
      dicistronic and includes the open reading frames of both Adh and Adhr. The
      dicistronic transcript is found in polysomes and the Adhr protein product is
      detected by antibody staining. We present evidence that the accumulation of the
      dicistronic mRNA is controlled at the level of the 3' end processing.

PMID- 9155027
TI  - A CREB-binding site as a target for decapentaplegic signalling during Drosophila
      endoderm induction.
AB  - Decapentaplegic (Dpp) is an extracellular signal of the transforming growth
      factor-beta family with multiple functions during Drosophila development. For
      example, it plays a key role in the embryo during endoderm induction. During this
      process, Dpp stimulates transcription of the homeotic genes Ultrabithorax in the
      visceral mesoderm and labial in the subjacent endoderm. Here, we show that a cAMP
      response element (CRE) from an Ultrabithorax enhancer mediates Dpp-responsive
      transcription in the embryonic midgut, and that endoderm expression from a labial
      enhancer depends on multiple CREs. Furthermore, the Drosophila CRE-binding
      protein dCREB-B binds to the Ultrabithorax CRE, and ubiquitous expression of a
      dominant-negative form of dCREB-B suppresses CRE-mediated reporter gene
      expression and reduces labial expression in the endoderm. Therefore, a CREB
      protein may act as a nuclear target, or as a partner of a nuclear target, for Dpp
      signalling in the embryonic midgut.

PMID- 9155029
TI  - A model for extradenticle function as a switch that changes HOX proteins from
      repressors to activators.
AB  - The Drosophila EXD protein and its mammalian counterparts, the PBX proteins, have
      been proposed to function in HOX target selectivity. Here we show that exd
      function is required for the autoactivation phase of Dfd expression in the
      posterior head. Mutations that change the affinity of a small autoactivation
      element for EXD protein result in corresponding changes in the element's
      embryonic activity. Our data suggest that the EXD and DFD proteins directly
      activate this element in maxillary cells without cooperatively binding to a
      specialized heterodimer binding site. Based on the types of homeotic
      transformations and changes in gene expression observed in exd mutant embryos, we
      propose a new model for EXD/PBX action in which these proteins are required for
      HOX protein transcriptional activation functions, but dispensable for HOX
      transcriptional repression functions. Although the selection of a specific target
      gene by a HOX protein versus another may be explained in some cases by the
      selective modulation of HOX binding specificity by EXD, we favor the idea that
      EXD interacts in a more general sense with most HOX proteins to switch them into
      a state where they are capable of transcriptional activation.

PMID- 9155030
TI  - Linker length and composition influence the flexibility of Oct-1 DNA binding.
AB  - POU domain transcription factors have two separate helix-turn-helix DNA-binding
      subdomains, the POU homeodomain (POUhd) and the POU-specific domain (POUs). Each
      subdomain recognizes a specific subsite of 4 or 5 bp in the octamer recognition
      sequence. The Oct-1 POU subdomains are connected by a 23 amino acid unstructured
      linker region. To investigate the requirements for the linker and its role in DNA
      recognition, we constructed POU domains in which the subdomains are connected
      with linkers varying in length between 2 and 37 amino acids. Binding to the
      natural octamer site required a minimal linker length of between 10 and 14 amino
      acids. A POU domain with an eight amino acid linker, however, had a high affinity
      for a site in which the POUs recognition sequence was inverted. Computer
      modelling shows that inversion of the POUs subdomain shortens the distance
      between the subdomains sufficiently to enable an eight amino acid linker to
      bridge the distance. DNase I footprinting as well as mutation of the POUs-binding
      site confirms the inverted orientation of the POUs domain. Switching of the POUs
      and POUhd subdomains and separation by 3 bp leads to a large distance which could
      only be bridged effectively by a long 37 amino acid linker. In addition to linker
      length, mutation of a conserved glutamate residue in the linker affected binding.
      As shown by surface plasmon resonance measurements, this was caused by a decrease
      in the on-rate. Our data indicate that there are both length and sequence
      requirements in the linker region which allow flexibility leading to selective
      binding to differently spaced and oriented subsites.

PMID- 9155031
TI  - mof, a putative acetyl transferase gene related to the Tip60 and MOZ human genes
      and to the SAS genes of yeast, is required for dosage compensation in Drosophila.
AB  - Dosage compensation is a regulatory process that insures that males and females
      have equal amounts of X-chromosome gene products. In Drosophila, this is achieved
      by a 2-fold enhancement of X-linked gene transcription in males, relative to
      females. The enhancement of transcription is mediated by the activity of a group
      of regulatory genes characterized by the male-specific lethality of their loss-of
      function alleles. The products of these genes form a complex that is
      preferentially associated with numerous sites on the X chromosome in somatic
      cells of males but not of females. Binding of the dosage compensation complex is
      correlated with a significant increase in the presence of a specific histone
      isoform, histone 4 acetylated at Lys16, on this chromosome. Experimental results
      and sequence analysis suggest that an additional gene, males-absent on the first
      (mof), encodes a putative acetyl transferase that plays a direct role in the
      specific histone acetylation associated with dosage compensation. The predicted
      amino acid sequence of MOF exhibits a significant level of similarity to several
      other proteins, including the human HIV-1 Tat interactive protein Tip60, the
      human monocytic leukemia zinc finger protein MOZ and the yeast silencing proteins
      SAS3 and SAS2.

PMID- 9155032
TI  - Mechanistic analysis of RNA polymerase III regulation by the retinoblastoma
      protein.
AB  - The tumour suppressor protein RB restricts cellular growth. This may involve
      inhibiting the synthesis of tRNA and 5S rRNA by RNA polymerase (pol) III. We have
      shown previously that RB can repress pol III transcription when overexpressed
      either in vitro or in vivo. We also demonstrated that pol III activity is
      elevated substantially in primary fibroblasts from RB-deficient mice. Here we
      address the molecular mechanism of this regulation. RB is shown to repress all
      types of pol III promoter. It can do this even if added after transcription
      complex assembly. Functional assays demonstrate that RB targets specifically the
      general pol III factor TFIIIB. A physical interaction between TFIIIB and RB is
      indicated by fractionation, pull-down and immunoprecipitation data. We show that
      TFIIIB activity is elevated in primary fibroblasts from RB-deficient mice. TFIIIB
      is a multisubunit complex that includes the TATA-binding protein (TBP) and a
      TFIIB-related factor called BRF. We show that RB itself contains regions of
      homology to both TBP and BRF and propose a model in which RB disrupts TFIIIB by
      mimicking these two components.

PMID- 9155033
TI  - The binding of a Fos/Jun heterodimer can completely disrupt the structure of a
      nucleosome.
AB  - An important first step in the chromatin remodelling process is the initial
      binding of a transcriptional activator to a nucleosomal template. We have
      investigated the ability of Fos/Jun (a transcriptional activator involved in the
      signal transduction pathway) to interact with its cognate binding site located in
      the promoter region of the mouse fos-related antigen-2 (fra-2) promoter, when
      this site was reconstituted into a nucleosome. Two different nucleosome assembly
      systems were employed to assemble principally non-acetylated or acetylated
      nucleosomes. The ability of Fos/Jun to interact with an acetylated or an
      unacetylated nucleosome differed markedly. Fos/Jun bound to an unacetylated
      nucleosome with only a 4- to 5-fold reduction in DNA binding affinity compared
      with naked DNA. Strikingly, the binding of Fos/Jun to a single high-affinity site
      incorporated into an acetylated nucleosome resulted in the complete disruption of
      nucleosomal structure without histone displacement. Moreover, this disruption was
      sufficient to facilitate the subsequent binding of a second transcription factor.

PMID- 9155034
TI  - Effects of Sin- versions of histone H4 on yeast chromatin structure and function.
AB  - Previous studies have identified single amino acid changes within either histone
      H3 or H4 (Sin- versions) that allow transcription in the absence of the yeast SWI
      SNF complex. The histone H4 mutants are competent for nucleosome assembly in
      vivo, and the residues that are altered appear to define a discrete domain on the
      surface of the histone octamer. We have analyzed the effects of the Sin- versions
      of histone H4 on transcription and chromatin structure in vivo. These histone H4
      mutants cause an increased accessibility of nucleosomal DNA to Dam
      methyltransferase and to micrococcal nuclease. Sin- derivatives of histone H4
      also grossly impair the ability of nucleosomes to constrain supercoils in vivo.
      Nucleosome-mediated repression of the PHO5 gene is severely impaired by these
      histone H4 mutants; PHO5 expression is derepressed to 31% of the wild-type
      induced level. In contrast to the induction caused by nucleosome depletion, full
      PHO5 derepression by Sin- versions of histone H4 requires upstream regulatory
      elements. In addition, Sin- derivatives of histone H4 do not activate expression
      from CYC1 or GAL1 promoters that lack UAS elements. We propose that these Sin-
      mutations alter histone-DNA contact residues that play key roles in restricting
      the accessibility of nucleosomal DNA to transcription factors.

PMID- 9155035
TI  - Histone acetylation: influence on transcription, nucleosome mobility and
      positioning, and linker histone-dependent transcriptional repression.
AB  - We demonstrate using a dinucleosome template that acetylation of the core
      histones enhances transcription by RNA polymerase III. This effect is not
      dependent on an increased mobility of the core histone octamer with respect to
      DNA sequence. When linker histone is subsequently bound, we find both a reduction
      in nucleosome mobility and a repression of transcription. These effects of linker
      histone binding are independent of core histone acetylation, indicating that core
      histone acetylation does not prevent linker histone binding and the concomitant
      transcriptional repression. These studies are complemented by the use of a
      Xenopus egg extract competent both for chromatin assembly on replicating DNA and
      for RNA polymerase III transcription. Incorporation of acetylated histones and
      lack of linker histones together facilitate transcription by >10-fold in this
      system; however, they have little independent effect on transcription. Thus core
      histone acetylation significantly facilitates transcription, but this effect is
      inhibited by the assembly of linker histones into chromatin.

PMID- 9155036
TI  - Protein-induced fit: the CRP activator protein changes sequence-specific DNA
      recognition by the CytR repressor, a highly flexible LacI member.
AB  - The CytR repressor and the cAMP receptor protein (CRP) bind cooperatively to
      several promoters in Escherichia coli to repress transcription initiation. The
      synergistic binding is mediated by protein-protein interactions between the two
      regulators. Here, in vitro selection experiments have been used to examine the
      DNA-binding characteristics of CytR, by itself and when co-binding with cAMP-CRP.
      We show that the optimal CytR-binding site consists of two octamer repeats, in
      direct or inverted orientation, and separated by 2 bp. However, when co-binding
      with cAMP-CRP, CytR instead recognizes inverted repeats separated by 10-13 bp, or
      direct repeats separated by 1 bp. The configurations of the latter set of
      operators correlate well with the configurations of natural CytR targets. Thus,
      cAMP-CRP induces conformational changes in CytR so that the repressor fits the
      natural targets. Most strikingly, CytR can adopt widely different conformations
      that are equally favored energetically for complex formation with cAMP-CRP. We
      propose that this structural adaptability is essential for CytR repression of
      promoters with diverse architectures. We discuss these novel concepts in the
      context of the CRP/CytR regulatory system, as well as the structural and
      functional implications for multiprotein-DNA complex formation in general.

PMID- 9155037
TI  - Site-specific deoxynucleotide substitutions in yeast U6 snRNA block splicing of
      pre-mRNA in vitro.
AB  - We have identified 2'-hydroxyl groups of the U6 phosphate-ribose backbone which
      are required for reconstitution of splicing activity in U6-depleted yeast
      extract. To screen the 2'-hydroxyls of yeast U6 at nucleotides 39-88, spanning
      the conserved central domain, synthetic U6 RNAs were constructed with
      deoxyribonucleotides incorporated site specifically. Only four individual
      deoxynucleotide substitutions blocked splicing activity: dA51 (in the ACAGAG
      sequence), dA62 (next to the AGC triad), and dU70 and dC72 (both in the loop of
      the 3' intramolecular stem-loop). Native gel analysis revealed that these deoxy
      substituted U6 RNAs were competent for assembly of spliceosomes. Interestingly, a
      2'-O-methyl substituent at A51, A62, U70 or C72 did not inhibit splicing
      activity, indicating that the essential 2'-OH groups at these positions in U6 act
      as hydrogen bond acceptors or neutral coordinated ligands. The requisite 2'
      hydroxyls at A62, U70 and C72 show both similarities and differences relative to
      the positions of essential 2'-hydroxyls of catalytic domain V of group II
      ribozymes. The identification of the essential 2'-hydroxyls at positions 62, 70
      and 72 corroborates that the 3' intramolecular stem-loop in U6 plays an important
      role in pre-mRNA splicing.

PMID- 9155038
TI  - Identification of HuR as a protein implicated in AUUUA-mediated mRNA decay.
AB  - Expression of many proto-oncogenes, cytokines and lymphokines is regulated by
      targeting their messenger RNAs for rapid degradation. Essential signals for this
      control are AU-rich elements (AREs) in the 3' untranslated region (UTR) of these
      messages. The ARE is loosely defined as the five-nucleotide sequence AUUUA
      embedded in a uracil-rich region. A transacting factor, presumably a protein,
      binds the ARE and initiates recognition by the destabilization machinery.
      Numerous candidate ARE-binding proteins have been proposed. We show that a 32 kDa
      protein in HeLa nuclear extracts characterized previously has RNA-binding
      specificity that correlates with the activity of an ARE in directing mRNA decay.
      Purification and subsequent analyses demonstrate that this 32 kDa protein is
      identical to a recently identified member of the Elav-like gene family (ELG)
      called HuR. The in vitro binding selectivity of HuR is indicative of an ARE
      sequence's ability to destabilize a mRNA in vivo, suggesting a critical role for
      HuR in the regulation of mRNA degradation.

PMID- 9155039
TI  - A ribonuclease specific for inosine-containing RNA: a potential role in antiviral
      defence?
AB  - RNA transcripts in which all guanosine residues are replaced by inosine are
      degraded at a highly accelerated rate when incubated in extracts from HeLa cells,
      sheep uterus or pig brain. We report here the partial purification and
      characterization of a novel ribonuclease, referred to as I-RNase, that is
      responsible for the degradation of inosine-containing RNA (I-RNA). I-RNase is
      Mg2+ dependent and specifically degrades single-stranded I-RNA. Comparison of the
      Km of the enzyme for I-RNA with the Ki for inhibition by normal RNA suggests a
      approximately 300-fold preferential binding to I-RNA, which can account for the
      specificity of degradation. The site of cleavage by I-RNase is non-specific; I
      RNase acts as a 3'-->5' exonuclease generating 5'-NMPs as products. The presence
      of alternative unconventional nucleotides in RNA does not result in degradation
      unless inosine residues are also present. We show that I-RNase is able to degrade
      RNAs that previously have been modified by the RED-1 double-stranded RNA
      adenosine deaminase (dsRAD). dsRADs destabilize dsRNA by converting adenosine to
      inosine, and some of these enzymes are interferon inducible. We therefore
      speculate that I-RNase in concert with dsRAD may form part of a novel cellular
      antiviral defence mechanism that acts to degrade dsRNA.

PMID- 9155040
TI  - Chromatin structure modulates DNA repair by photolyase in vivo.
AB  - Yeast and many other organisms use nucleotide excision repair (NER) and
      photolyase in the presence of light (photoreactivation) to repair cyclobutane
      pyrimidine dimers (CPDs), a major class of DNA lesions generated by UV light. To
      study the role of photoreactivation at the chromatin level in vivo, we used yeast
      strains which contained minichromosomes (YRpTRURAP, YRpCS1) with well
      characterized chromatin structures. The strains were either proficient (RAD1) or
      deficient (rad1 delta) in NER. In contrast to NER, photolyase rapidly repairs
      CPDs in non-nucleosomal regions, including promoters of active genes (URA3, HIS3,
      DED1) and in linker DNA between nucleosomes. CPDs in nucleosomes are much more
      resistant to photoreactivation. These results demonstrate a direct role of
      chromatin in modulation of a DNA repair process and an important role of
      photolyase in repair of damaged promoters with presumptive effects on gene
      regulation. In addition, photoreactivation provides an in vivo test for chromatin
      structure and stability. In active genes (URA3, HIS3), photolyase repairs the non
      transcribed strand faster than the transcribed strand and can match fast removal
      of lesions from the transcribed strand by NER (transcription-coupled repair).
      Thus, the combination of both repair pathways ensures efficient repair of active
      genes.

PMID- 9155041
TI  - Septal localization of the SpoIIIE chromosome partitioning protein in Bacillus
      subtilis.
AB  - The 787 amino acid SpoIIIE protein of Bacillus subtilis is required for
      chromosome partitioning during sporulation. This process differs from vegetative
      chromosome partitioning in that it occurs after formation of the septum,
      apparently by transfer of the chromosome through the nascent septum in a manner
      reminiscent of plasmid conjugation. Here we show that SpoIIIE is associated with
      the cell membrane, with its soluble C-terminal domain located inside the cell.
      Immunofluorescence microscopy using affinity-purified anti-SpoIIIE antibodies
      shows that SpoIIIE is targeted near the centre of the asymmetric septum, in
      support of a direct role for SpoIIIE in transport of DNA through the septum. We
      also report on the isolation of a mutation affecting the N-terminal hydrophobic
      domain of SpoIIIE that interferes with targeting to the septum and blocks DNA
      transfer. This mutation also causes de-localization of the activity of the
      normally prespore-specific sigma factor, sigmaF, consistent with the notion that
      SpoIIIE can form a seal between the chromosomal DNA and the leading edge of the
      division septum.

PMID- 9155042
TI  - Resistance of ovarian teratocarcinoma cell spheroids to complement-mediated
      lysis.
AB  - We have shown previously that it is possible to target complement-mediated
      killing against cultured ovarian tumour cells in vitro. As malignant ovarian
      cells usually grow in solid nodules in vivo, we have in the present study
      examined the effectiveness of complement killing against ovarian teratocarcinoma
      cells (PA-1) growing in three-dimensional tumour microspheroids (TMSs). Our study
      shows that PA-1 cells growing in TMSs are less susceptible to complement-mediated
      killing than cells growing in monolayer cultures, even after neutralization of
      protectin (CD59), the main inhibitor of complement lysis. Cells in suspension and
      cells growing in TMSs showed a similar expression of membrane co-factor protein
      (MCP, CD46) and CD59. Decay-accelerating factor (DAF, CD55) was not detected on
      the surface of cells in suspension, but appeared focally on the outermost cell
      layers of the TMSs. Complement-activating antibodies bound to all PA-1 cells in
      suspension but only to the most peripherally located cells in TMSs, even though
      the target antigens were similarly expressed in the two systems. Antibody-induced
      complement activation on PA-1 cells in suspension led to C3 and C5b-9 deposition
      on most cells, while C3 and C5b-9 were only found on the outermost layers of the
      TMSs. The increased complement resistance of tumour cells growing in three
      dimensional spheroids is partly because of an insufficient penetration of
      antibodies and complement into the TMSs. TMSs are a useful model for the
      development of more efficient ways to kill malignant cells in micrometastases
      with monoclonal antibodies and complement.

PMID- 9155043
TI  - Ovarian cancer has frequent loss of heterozygosity at chromosome 12p12.3-13.1
      (region of TEL and Kip1 loci) and chromosome 12q23-ter: evidence for two new
      tumour-suppressor genes.
AB  - Identification of the key genetic alterations leading to ovarian cancer is in its
      infancy. Polymerase chain reaction (PCR)-based analysis of loss of heterozygosity
      (LOH) is a powerful method for detecting regions of altered tumour-suppressor
      genes. Focusing on chromosome 12, we examined 23 ovarian cancer samples for LOH
      using 31 highly polymorphic microsatellite markers and found the chromosomal
      localization of two putative tumour-suppressor genes. Two commonly deleted
      regions were 12p12.3-13.1 in 6/23 (26%) and 12q23-ter in 7/23 (30%) samples. LOH
      on chromosome 12 was more common in late-stage ovarian carcinomas. The region of
      LOH at 12p12.3-13.1 includes the genes that code for the ETS-family
      transcriptional factor, known as TEL, and the cyclin-dependent kinase inhibitor,
      known as p27Kip1. Mutational analysis of both TEL and p27Kip1 using single-strand
      conformation polymorphism (SSCP) showed no abnormalities, suggesting that the
      altered gene in this region is neither of these genes. Taken together, our data
      suggest that new tumour-suppressor genes in the region of chromosomes 12p12.3
      13.1 and 12q23-ter may be involved in the development of ovarian cancer.

PMID- 9155044
TI  - Expression of cyclin D1 correlates with malignancy in human ovarian tumours.
AB  - Cyclin D1 is a cell cycle regulator of G1 progression that has been suggested to
      play a relevant role in the pathogenesis of several human cancer types. In the
      current study, the expression of cyclin D1 has been investigated in a series of
      33 patients, with benign (10 patients), borderline (five patients) and malignant
      (18 patients) ovarian disease. Cyclin D1 protein and mRNA content were analysed
      by Western blotting and reverse transcriptase polymerase chain reaction
      respectively. The levels of cyclin D1 protein were undetectable in patients with
      benign disease, detectable in the majority of patients with borderline disease
      and elevated in those with ovarian carcinomas, being significantly related to the
      degree of malignancy (carcinoma vs benign, P = 0.0001; benign vs borderline, P =
      0.0238). A significant relationship between cyclin D1 expression and tumour
      proliferative activity was also found (P = 0.000001). Moreover, eight benign
      lesions, two borderline tumours and 11 carcinomas proved to be suitable for the
      analysis of cyclin D1 transcript, and emerging data demonstrated significant
      agreement between protein abundance and mRNA expression. Results from the current
      study suggest that cyclin D1 expression is associated with the degree of
      transformation and most probably plays a role in the early development of ovarian
      malignancy.

PMID- 9155045
TI  - MDM2 and p53 expression in gliomas: a multivariate survival analysis including
      proliferation markers and epidermal growth factor receptor.
AB  - p53 and the murine double minute 2 (MDM2) oncoprotein expression was evaluated in
      paraffin-embedded tissue from 61 patients with central nervous system gliomas (53
      astrocytomas and eight oligodendrogliomas) and related to proliferation
      associated markers [i.e. proliferating cell nuclear antigen (PCNA), Ki-67 and
      nuclear organizer regions (NORs)] and epidermal growth factor receptor (EGFR). We
      used the monoclonal antibodies PC-10, MIB-1, DO-1, 1B1O and EGFR 113 and the
      colloid silver nitrate (AgNOR) technique. MDM2 and p53 were co-expressed in 28%
      of cases. A p53-positive/MDM2-negative phenotype was observed in 15% and a p53
      negative/MDM2-positive phenotype in 20% of cases. There was a positive
      correlation of p53 and MDM2 expression with grade and proliferation indices.
      Univariate analysis in the group of diffuse astrocytomas showed that older age,
      high histological grade, high PCNA labelling index (LI) and high AgNOR score were
      associated with reduced overall survival (P < 0.05). p53 LI, Ki-67 LI, AgNOR
      score, tumour location and grade influenced disease-free survival (P < 0.05),
      whereas the only parameters affecting post-relapse survival were histological
      grade and Ki-67 LI (P < 0.1). Multivariate analysis revealed that age,
      radiotherapy, PCNA LI and p53 LI were the independent predictors of overall
      survival. p53 LI, Ki-67 LI, MDM2 LI, EGFR LI, grade and type of therapy were
      independent predictors of disease-free survival, and grade was the only
      independent predictor of post-relapse survival. Our results indicate that p53 LI
      and MDM2 LI, EGFR expression as well as proliferation markers (PCNA and Ki-67)
      are useful indicators of overall and disease-free survival in diffuse astrocytoma
      patients.

PMID- 9155046
TI  - Angiotensin II type 1 receptor expression in human breast tissues.
AB  - We demonstrate the expression of angiotensin II type 1 (AT1) receptors in normal
      and diseased human breast tissues. Using monoclonal antibody 6313/G2, directed
      against a specific sequence in the extracellular domain of the AT1 receptor,
      immunocytochemical analysis revealed positive immunoreactivity in membrane and
      cytoplasm of specific cell types. Immunoblotting of solubilized proteins
      separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS
      PAGE) from benign and malignant tumours identified a single immunoreactive
      species with a molecular mass of approximately 60 kDa, consistent with that of
      the mature glycosylated receptor. In studies of [125I]angiotensin II binding
      using breast membrane preparations, concentrations of specific angiotensin II
      binding sites were found to range from 1.8 to 100 fmol mg(-1) protein, with a
      K(d) of approximately 60 nM. Most of the specifically bound [125I]angiotensin II
      was displaced by losartan, a specific angiotensin II type 1 receptor antagonist,
      while less was displaced by the AT2 receptor type antagonist, CGP42112A, thus
      confirming the prevalence of AT1 receptors in this tissue type. These data
      suggest that the renin-angiotensin system may be involved in normal and abnormal
      breast tissue function.

PMID- 9155047
TI  - All-trans retinoic acid decreases susceptibility of a gastric cancer cell line to
      lymphokine-activated killer cytotoxicity.
AB  - All-trans retinoic acid (RA) was previously shown to regulate the growth of
      gastric cancer cells derived from the cell line SC-M1. This study was designed to
      investigate the effect of RA on the sensitivity of SC-M1 cells to lymphokine
      activated killer (LAK) activity. RA at the concentration range of 0.001-10 microM
      was shown to induce SC-M1 cells to exhibit resistance to LAK activity in a dose
      dependent manner. A kinetics study indicated that a significantly increased
      resistance was detected after 2 days of co-culturing SC-M1 cells with RA and
      reached a maximum after 6 days of culture. Similar results were obtained from two
      other cancer cell lines: promyelocytic leukaemia HL-60 and hepatic cancer Hep 3B.
      A binding assay demonstrated that the binding efficacy between target SC-M1 cells
      and effector LAK cells was not altered by RA. Flow cytometric analyses revealed
      that RA exhibited no effect on the expression of cell surface molecules,
      including HLA class I and class II antigens, intercellular adhesion molecule-1
      and -2, and lymphocyte function antigen-3. Cell cycle analysis revealed that
      culture of SC-M1 cells with RA resulted in an increase in G0/G1 phase and a
      decrease in S phase, accompanied by a decrease in cyclin A and cyclin B1 mRNA as
      determined by Northern blot analysis. Additionally, RA was shown to enhance the
      expression of retinoic acid receptor alpha (RAR alpha) in SC-M1 cells, and to
      have no effect on the expression of RARbeta or RARgamma. Taken together, these
      results indicate that RA can significantly increase gastric cancer cells SC-M1 to
      resist LAK cytotoxicity by means of a cytostatic effect through a mechanism
      relating to cell cycle regulation. The prevailing ideas, such as a decrease in
      effector to target cell binding, a reduced MHC class I antigen expression or an
      altered RARbeta expression, are not involved.

PMID- 9155048
TI  - The Rhesus D-negative phenotype is an independent predictor of poor prognosis in
      curatively (RO) resected gastric cancer patients.
AB  - Among gastric cancer patients, the Rhesus D-negative phenotype correlated with
      increased tumour recurrence [all patients, n = 83, P = 0.026; curatively (R0)
      resected patients, n = 51, P = 0.093] and reduced overall survival time (all
      patients, log-rank P = 0.0028; R0 patients, log-rank P = 0.0003) and was
      identified in multivariate analysis as the most important independent prognostic
      marker in the R0 patient group (relative risk 9.1, P = 0.0013).

PMID- 9155049
TI  - Neoangiogenesis and p53 protein in lung cancer: their prognostic role and their
      relation with vascular endothelial growth factor (VEGF) expression.
AB  - Following up-regulation of an angiogenesis inhibitor by the wild-type p53 protein
      proven recently, we have analysed on the one hand the prognostic impact of
      microvessel count (MC) and p53 protein overexpression in non-small-cell lung
      carcinoma (NSCLC) progression and, on the other hand, the inter-relation between
      the microvascular pattern and the p53 protein expression. Moreover, we assessed
      the expression of vascular endothelial growth factor (VEGF), one of the pivotal
      mediators of tumour angiogenesis, in order to investigate its relation to p53
      protein expression and MC. Tumours from 73 patients resected for NSCLC between
      March 1991 and April 1992 (median follow-up 47 months, range 32-51 months) were
      analysed using an immunohistochemical method. In univariate analysis, MC and p53
      accumulation were shown to affect metastatic nodal involvement, recurrence and
      death significantly. Multiple logistic regression analysis showed an important
      prognostic influence of MC and nodal status on overall (P = 0.0009; P = 0.01) and
      disease-free survival (P = 0.0001; P = 0.03). Interestingly, a strong statistical
      association was observed between p53 nuclear accumulation and MC (P = 0.0003).
      The same inter-relationship was found in non-squamous histotype (P = 0.002). When
      we analysed the concomitant influence of MC and p53 expression on overall
      survival, we were able to confirm a real predominant role of MC in comparison
      with p53. With regard to VEGF expression, p53-negative and lowly vascularized
      tumours showed a mean VEGF expression significantly lower than p53-positive and
      highly vascularized cancers (P = 0.02). These results underline the prognostic
      impact of MC and p53 protein accumulation in NSCLC and their reciprocal inter
      relationship, supporting the hypothesis of a wild-type p53 regulation on the
      angiogenetic process through a VEGF up-regulation.

PMID- 9155050
TI  - MDM2 gene amplification and expression in non-small-cell lung cancer:
      immunohistochemical expression of its protein is a favourable prognostic marker
      in patients without p53 protein accumulation.
AB  - MDM2 is an oncoprotein that inhibits p53 tumour-suppressor protein. Amplification
      of the MDM2 gene and overexpression of its protein have been observed in some
      human malignancies, and these abnormalities have a role in tumorigenesis through
      inactivation of p53 function. To determine the clinicopathological and prognostic
      value of MDM2 abnormalities in non-small-cell lung cancer (NSCLC), MDM2 gene
      amplification and its protein expression status were analysed in surgically
      resected materials. MDM2 gene amplification was detected in only 2 (7%) of the 30
      tested patients. MDM2 protein was found immunohistochemically in a total of 48
      (24%) of the 201 patients. MDM2 protein was slightly frequently observed in
      patients with adenocarcinoma, but its presence or absence was not associated with
      clinicopathological factors such as T-factor, N-factor, stage, tumour size,
      differentiation or p53 protein status. Overall, MDM2-positive patients tended to
      have a better prognosis (P = 0.062). In particular, among immunohistochemically
      p53-negative patients (n = 110), those with positive MDM2 protein expression
      showed significantly better prognosis (P = 0.039) and, in a multivariate
      analysis, MDM2 protein status was a favourable prognostic factor (P = 0.037). In
      contrast, among p53-positive patients (n = 91), there was no difference in
      prognosis depending on MDM2 protein status. Thus, in the NSCLC patients studied,
      MDM2 gene amplification was a minor event, but expression of its protein, which
      was often observed immunohistochemically, was a favourable prognostic marker,
      especially among patients without p53 protein accumulation. Further study is
      needed to determine how MDM2 protein expression results in a better prognosis.

PMID- 9155051
TI  - Frequent reduction or loss of DCC gene expression in human osteosarcoma.
AB  - The 'deleted in colon carcinoma' (DCC) gene has been considered a candidate
      tumour-suppressor gene that encodes for a transmembrane protein with strong
      structural similarity to members of the superfamily of neural cell adhesion
      molecules. It has been mapped to the chromosomal region 18q21.1 and it is
      implicated in cellular differentiation and developmental processes. In human
      osteosarcoma allelic loss frequently occurs on the long arm of chromosome 18,
      suggesting a possible involvement of the DCC gene in the pathogenesis of this
      tumour entity. In the present study the mRNA and protein expression and
      rearrangements at the DNA level of the DCC gene were addressed in 25
      osteosarcomas and several tumour cell lines, including osteosarcoma- and colon
      carcinoma-derived cell lines. Using an reverse transcriptase polymerase chain
      reach in (RT-PCR)-based approach DCC expression was found to be lost or
      substantially reduced in 14 of 19 high-grade osteosarcomas, in three of six lower
      grade osteosarcomas and most of the tumour cell lines, in contrast to normally
      differentiated osteoblasts. Immunohistochemical studies on DCC protein expression
      of 14 selected tumours correlated well with the RT-PCR-based results. In view of
      the putative tumour-suppressor characteristics of the DCC gene its loss or
      reduction of expression could be a specific event in the development or
      progression of many high-grade osteosarcomas.

PMID- 9155052
TI  - Early-onset breast cancer--histopathological and prognostic considerations.
AB  - Young age at diagnosis is claimed to be a prognostic factor in the natural
      history of breast cancer. Of 2879 patients aged < 70 years treated for primary
      operable breast cancer (< 5 cm diameter) at Nottingham City Hospital between 1973
      and 1993, 120 were less than 35 years of age at diagnosis. Histopathological and
      prognostic variables were compared between patients aged < 35, 35-50 and 51-70
      years. A significant reduction in metastasis disease-free survival and actuarial
      survival was seen in breast cancer patients aged < 35 years compared with the two
      older age groups. Patients aged < 35 years at diagnosis presented more frequently
      with high-grade cancers and vascular invasion. No differences were seen for
      tumour size or lymph node stage. The Nottingham Prognostic Index (NPI) was used
      to stratify cancers in each age group. Because of the tendency to high grade, a
      greater percentage of patients aged < 35 years fell into the poor-prognosis
      group. Within each prognostic group, no difference in actuarial survival was seen
      between age groups. The association of young age at diagnosis with a worse
      prognosis in this series is explained by a higher proportion of poorly
      differentiated cancers; age itself had no influence on the prognosis of the
      individual.

PMID- 9155053
TI  - Loss of heterozygosity at chromosome 6q in preinvasive and early invasive breast
      carcinomas.
AB  - We have used polymerase chain reaction (PCR) analysis to study the incidence of
      allelic imbalance at four polymorphic microsatellite markers on chromosome 6q25.1
      27, three dinucleotide repeats and one trinucleotide repeat, for microdissected
      tumour foci from a group of 75 'early' breast carcinomas. The tumours comprised
      16 preinvasive cases of ductal carcinoma in situ (DCIS) and 59 mammographically
      detected early invasive carcinomas. Loss of heterozygosity (LOH) was detected at
      all four loci and in all types and grade of disease. The frequency of LOH ranged
      from 23% to 50% depending on the marker studied. The highest frequency of LOH was
      observed at the D6S186 locus for the cases of DCIS and at the oestrogen receptor
      locus for the invasive carcinomas. These data suggest that the inactivation of
      tumour-suppressor genes within this region on chromosome 6q is important for the
      development of these early lesions.

PMID- 9155054
TI  - Co-ordinate loss of protein kinase C and multidrug resistance gene expression in
      revertant MCF-7/Adr breast carcinoma cells.
AB  - The aim of this study was to investigate the link between protein kinase C (PKC)
      and multidrug resistance (mdr) phenotype. The expression of both was studied in
      doxorubicin-resistant MCF-7/Adr cells as they reverted to the wild-type phenotype
      when cultured in the absence of drug. The following parameters were measured in
      cells 4, 10, 15, 20 and 24 weeks after removal of doxorubicin; (1) sensitivity of
      the cells towards doxorubicin; (2) levels of P-glycoprotein (P-gp) and MDR1 mRNA;
      (3) levels and cellular localization of PKC isoenzyme proteins alpha, theta and
      epsilon; and (4) gene copy number of PKC-alpha and MDR1 genes. Cells lost their
      resistance gradually with time, so that by week 24 they had almost completely
      regained the drug sensitivity seen in wild-type MCF-7 cells. P-gp levels measured
      by Western blot mirrored the change in doxorubicin sensitivity. By week 20, P-gp
      had decreased to 18% of P-gp protein levels at the outset, and P-gp was not
      detectable at week 24. Similarly, MDR1 mRNA levels had disappeared by week 24.
      MCF-7/Adr cells expressed more PKCs-alpha and -theta than wild-type cells and
      possessed a different cellular localization of PKC-epsilon. The expression and
      distribution pattern of these PKCs did not change for up to 20 weeks, but
      reverted back to that seen in wild-type cells by week 24. MDR1 gene amplification
      remained unchanged until week 20, but then was lost precipitously between weeks
      20 and 24. The PKC-alpha gene was not amplified in MCF-7/Adr cells. The results
      suggest that MCF-7/Adr cells lose MDR1 gene expression and PKC activity in a co
      ordinate fashion, consistent with the existence of a mechanistic link between
      MDR1 and certain PKC isoenzymes.

PMID- 9155055
TI  - Infrequent microsatellite instability in oesophageal cancers.
AB  - Alterations of microsatellites have been found at relatively high frequency in
      hereditary and sporadic colorectal cancer and gastric and pancreatic cancers and
      at lower frequency in some other cancers. We determined the frequency of
      instability at 39 poly-CA microsatellite loci in 20 squamous cell carcinomas and
      26 Barrett's adenocarcinomas of the oesophagus. None of the tumours presented
      instability for a high percentage of the tested loci. Four squamous cell
      carcinomas and six Barrett's adenocarcinomas showed microsatellite instability at
      one locus, and three Barrett's adenocarcinomas showed microsatellite instability
      at two loci. The presence of few loci showing microsatellite instability could be
      due to an instability background. We conclude that genetic defects in the DNA
      mismatch repair system do not play an important role in oesophageal cancers.

PMID- 9155056
TI  - The distribution and expression of the two isoforms of DNA topoisomerase II in
      normal and neoplastic human tissues.
AB  - In mammalian cells, there are two isoforms of DNA topoisomerase II, designated
      alpha (170-kDa form) and beta (180-kDa form). Previous studies using cell lines
      have shown that the topoisomerase IIalpha and beta isoforms are differentially
      regulated during the cell cycle and in response to changes in growth state.
      Moreover, both isoforms can act as targets for a range of anti-tumour drugs.
      Here, we have analysed the normal tissue distribution in humans of topoisomerase
      IIalpha and beta using isoform-specific antibodies. In addition, we have studied
      expression of these isoforms in 69 primary tumour biopsies, representative either
      of tumours that are responsive to topoisomerase II-targeting drugs (breast, lung,
      lymphoma and seminoma) or of those that show de novo drug resistance (colon).
      Topoisomerase IIalpha was expressed exclusively in the proliferating compartments
      of all normal tissues, and was detectable in both the cell nucleus and cytoplasm.
      In biologically aggressive or rapidly proliferating tumours (e.g. high-grade
      lymphomas and seminomas), there was a high level of topoisomerase IIalpha,
      although expression was still detectable in colon tumours, indicating that
      expression of this isoform is not sufficient to explain the intrinsic drug
      resistance of colon tumours. Topoisomerase IIbeta was expressed ubiquitously in
      vivo and was localized in both the nucleoli and the nucleoplasm. This isoform was
      present in quiescent cell populations, but was expressed at a generally higher
      level in all tumours and proliferating cells than in normal quiescent tissues. We
      conclude that topoisomerase IIalpha is a strict proliferation marker in normal
      and neoplastic cells in vivo, but that topoisomerase IIbeta has a much more
      general cell and tissue distribution than has topoisomerase IIalpha. The apparent
      up-regulation of topoisomerase IIbeta in neoplastic cells has implications for
      the response of patients to anti-tumour therapies that include topoisomerase II
      targeting drugs.

PMID- 9155057
TI  - Enhancement of immunotoxin activity using chemical and biological reagents.
AB  - One of the major discoveries of effective therapeutics is the use of targeted
      treatment, such as antibody-directed toxins, i.e. immunotoxins; however, this
      medicine delivery strategy is still at a developmental stage. A number of
      problems need to be resolved; one is their inefficacy when applied in vivo.
      Research has stimulated interest in this area through the use of chemical
      reagents and other moieties to increase the activity of immunotoxins. In this
      article, reagents that can potentiate the cytotoxicity of immunotoxins are
      reviewed and the mechanisms that increase activity of immunotoxins are discussed.
      Lysosomotropic amines, especially ammonium chloride and chloroquine, may raise
      the pH value of the lysosome in which the conjugates enter. Carboxylic
      ionophores, e.g. monensin, can influence Golgi vacuolation, which may facilitate
      the routing of conjugates, augmenting activity. Calcium channel antagonists may
      increase immunotoxin killing through morphological or other mechanisms that are
      not yet well understood. Viral particles and surface structure can enhance the
      cytotoxicity of conjugates, probably through the mechanism of disrupting
      endosomes. In addition, cytokines, beta-adrenergic blockers, immunosuppressive
      agents (cyclosporin A) and some antibiotics (daunorubicin) can be used to
      increase the effect of immunotoxins.

PMID- 9155058
TI  - The influence of ifosfamide scheduling on acute nephrotoxicity in children.
AB  - Nephrotoxicity is a significant problem in children after treatment with
      ifosfamide. Acute changes in renal function were compared in 16 children
      receiving 9 g m(-2) of ifosfamide as a 72-h continuous infusion on one occasion
      and, on another course, divided into three 1-h infusions on consecutive days.
      Subclinical acute nephrotoxicity was demonstrated with both schedules, but there
      were no significant differences in severity.

PMID- 9155059
TI  - Long-term prognostic and predictive factors in 107 stage II/III breast cancer
      patients treated with anthracycline-based neoadjuvant chemotherapy.
AB  - The heterogeneity of therapeutic modalities and eligibility criteria and the lack
      of long-term follow-up in most reports of neoadjuvant chemotherapy for breast
      cancer preclude us from drawing conclusions about its value in clinically
      relevant patient subgroups. The present study aims to identify predictive and
      prognostic factors in 107 non-inflammatory stage II/III breast cancer patients
      treated between November 1980 and October 1991 with an anthracycline-based
      induction regimen before locoregional surgery. Preoperative chemotherapy
      comprised 3-6 cycles of doxorubicin (pirarubicin after 1986), vindesine,
      cyclophosphamide and 5-fluorouracil. Type of subsequent surgery and adjuvant
      treatment were decided individually. In analysis of outcome, univariate
      comparisons of end points were made using the log-rank test, and significant (P <
      or = 0.05) pre- and post-therapeutic factors were incorporated in a Cox
      multivariate analysis. With a median follow-up of 81 months (range 32-164+
      months), the median disease-free survival (DFS) is 90.5 months while median
      overall survival has not yet been reached. Cytoprognostic grade and
      histopathological response in both the primary and lymph nodes were independent
      covariates associated with locoregional relapse with or without DFS and overall
      survival. Eleven patients with pathological complete response remain free of
      disease with a 68-month median follow-up, while the 18 with residual microscopic
      disease on the specimen showed a 60% cumulative incidence of locoregional
      recurrence. Despite encouraging response rates based on clinical or radiological
      evaluation (87% or 70%), neither method showed any significant correlation with
      pathological response and failed to contribute prognostic information on
      patients' outcome. Pathological evaluation of antitumoral activity of primary
      chemotherapy remains a major source of prognostic information and might be used
      to select patients in need of additional adjuvant treatment.

PMID- 9155061
TI  - Elevated serum levels of S100 and survival in metastatic malignant melanoma.
AB  - Current reports suggest serum S100 as a prognostic marker for disease progression
      in advanced malignant melanoma. In this study, we assessed serum levels of S100
      and multiple clinical factors in relation to overall survival in 99 patients with
      metastatic malignant melanoma seen at our institution between May 1990 and April
      1996. For statistical analysis, we used both univariate and multivariate Cox
      proportional-hazards models. Elevated serum levels of S100 correlated with poor
      outcome in metastatic malignant melanoma (P < 0.0001), univariate analysis). Upon
      multivariate analysis, however, S100 added no information to known clinical
      prognostic parameters.

PMID- 9155060
TI  - Collection of circulating progenitor cells after epirubicin, paclitaxel and
      filgrastim in patients with metastatic breast cancer.
AB  - The efficacy of high-dose chemotherapy (HDC) and circulating progenitor cell
      (CPC) transplantation in metastatic breast cancer (MBC) relies mainly on giving
      this treatment after a response to conventional induction chemotherapy has been
      achieved. For this reason an optimal mobilization regimen should be
      therapeutically effective while minimizing the number of leucaphereses required
      to support the myeloablative therapy. The combination of an anthracycline and
      paclitaxel in chemotherapy-untreated MBC has produced impressive response rates.
      We evaluated the CPC-mobilizing capacity of the combination epirubicin (90 mg m(
      2)) and paclitaxel (135 mg m(-2)) followed by filgrastim (5 microg kg(-1) day(
      1)) starting 48 h after chemotherapy administration in ten patients with MBC who
      were eligible for an HDC and CPC transplantation programme. Leucaphereses were
      performed by processing at least two blood volumes per procedure at recovery from
      neutrophil nadir when CD34+ cells in the peripheral blood exceeded 20 microl(-1).
      In most patients (six out of 10) more than 2.5 x 10(6) CD34+ cells kg(-1), a
      threshold considered to be sufficient for haematopoietic reconstitution, were
      collected with a single apheresis. In the remaining four patients an additional
      procedure, performed the following day, was enough to reach the required number
      of progenitors. These data suggest that the epirubicin-paclitaxel combination,
      besides being a very active regimen in MBC, is effective in releasing large
      amounts of progenitor cells into circulation.

PMID- 9155062
TI  - BRCA1 5382insC mutation in sporadic and familial breast and ovarian carcinoma in
      Scotland.
AB  - A restriction site-generating polymerase chain reaction (RG-PCR) assay was
      developed to detect the BRCA1 5382insC mutation that has been reported in
      multiple, apparently unrelated breast/ovarian carcinoma families. The assay has
      been used to screen tumour DNA from 250 breast cancer patients (aged 19-86 years)
      and from 80 ovarian cancer patients (aged 25-90 years) in a local population of
      patients with no known family history. Altogether, 0/80 (0%) ovarian and 1/250
      (0.4%) breast tumour DNAs were found to have the 5382insC mutation. The sole
      positive case was a 26-year-old woman (BC185) with no known family history. One
      of the reasons for carrying out this analysis was that the 5382insC mutation had
      previously been shown to segregate with the disease in a very large Scottish
      'West Lothian' kindred having breast/ovarian carcinoma. To investigate whether
      this apparently isolated case and the known family might be related, haplotypes
      for the markers D17S855, D17S1322, D17S1323 and D17S1327 were analysed. The
      mutant haplotype in the large kindred was identical to that reported in all other
      5382insC mutation families for all markers with the exception of D17S1327. This
      implies that there has been a recombination event at the telomeric end of common
      ancestral haplotype in this family. Since the isolated case we identified carries
      the 'complete' common haplotype, it is unlikely that she is closely related to
      the West Lothian family.

PMID- 9155063
TI  - Risk factors for colorectal cancer in subjects with family history of the
      disease.
AB  - The relationship between lifestyle factors, past medical conditions, daily meal
      frequency, diet and the risk of 'familial' colorectal cancer has been analysed
      using data from a case-control study conducted in northern Italy. A total of 1584
      colorectal cancer patients and 2879 control subjects were admitted to a network
      of hospitals in the Greater Milan area and the Pordenone province. The subjects
      included for analysis were the 112 cases and the 108 control subjects who
      reported a family history of colorectal cancer in first-degree relatives.
      Colorectal cancer cases and control subjects with family history were similarly
      distributed according to sex, age, marital status, years of schooling and social
      class. Familial colorectal cancer was associated with meal frequency, medical
      history of diabetes (relative risk, RR = 4.6) and cholelithiasis (RR = 5.2).
      Significant positive trends of increasing risk with more frequent consumption
      were observed for pasta (RR = 2.5, for the highest vs the lowest intake tertile),
      pastries (RR = 2.4), red meat (RR = 2.9), canned meat (RR = 1.9), cheese (RR =
      3.5) and butter (RR = 1.9). Significant inverse associations and trends in risk
      were observed for consumption of poultry (RR = 0.4), tomatoes (RR = 0.2), peppers
      (RR = 0.3) and lettuce (RR = 0.3). Significant inverse trends in risk with
      increasing consumption for beta-carotene and ascorbic acid were observed (RR =
      0.5 and 0.4 respectively, highest vs lowest intake tertile). These results
      suggest that risk factors for subjects with a family history of colorectal cancer
      in first-degree relatives are not appreciably different from recognized risk
      factors of the disease in the general population.

PMID- 9155064
TI  - Susceptibility to endometrial cancer: influence of allelism at p53, glutathione S
      transferase (GSTM1 and GSTT1) and cytochrome P-450 (CYP1A1) loci.
AB  - A case-control study was designed to identify associations between polymorphisms
      at p53, cytochrome P-450 (CYP1A1) and glutathione-S-transferases and endometrial
      cancer susceptibility. Among all polymorphisms analysed, an insertional variant
      in p53 (P53PIN3) and two polymorphisms in the 3'-end and exon 7 of CYP1A1 showed
      significant association with enhanced endometrial cancer risk.

PMID- 9155065
TI  - Alcohol, tobacco and oesophageal cancer: effects of the duration of consumption,
      mean intake and current and former consumption.
AB  - Numerous epidemiological studies have shown that alcohol and tobacco consumption
      are the main risk factors for oesophageal cancer in Western countries. In these
      studies, the consumption of both alcohol and tobacco has almost always been
      measured as current mean intake. The present case-control study investigates the
      association between alcohol and tobacco consumption and the risk of oesophageal
      cancer by assessing exposure as total lifetime intake, mean weekly intake,
      duration of consumption and former and current consumption. Between 1991 and
      1994, 208 cases and 399 control subjects were selected from three French
      university hospitals (Caen, Dijon and Toulouse). Eligible cases were men aged
      less than 85 years admitted to one of these hospitals with histologically proven
      squamous cell carcinoma of the oesophagus. During the interview, complete tobacco
      and alcohol consumption histories were recorded. Our findings suggest that
      alcohol consumption and tobacco consumption influence the risk of oesophageal
      cancer in different ways. In the case of alcohol, the relationship between the
      odds ratio and mean weekly intake was linear, the risk depending solely on mean
      weekly intake, with former and current consumption having similar effects. With
      regard to tobacco, the relationship between the odds ratio and mean weekly intake
      was log-linear; the risk depended mainly on the duration of consumption and
      former consumption had a lesser effect than current consumption. Our study
      suggests that total lifetime intake is not a correct measure of exposure for
      either alcohol or tobacco: for a given lifetime consumption of tobacco, a
      moderate intake during a long period carries a higher risk than a high intake
      during a shorter period and, conversely, for a given lifetime consumption of
      alcohol, a high intake during a shorter period carries a higher risk than a
      moderate intake during a longer period. Our results confirm the very low risk
      associated with a low alcohol intake, even over long periods. In contrast, there
      is a steep increase in the risk associated with smoking at even low mean intakes
      if these are continued over long periods. Our findings also suggest that even
      heavy smokers may benefit from quitting.

PMID- 9155066
TI  - A mutation in exon 7 of the human cytochrome P-4501A1 gene as marker for
      sensitivity to anti-cancer drugs?

PMID- 9155067
TI  - No association of a 306-bp insertion polymorphism in the progesterone receptor
      gene with ovarian and breast cancer.

PMID- 9155068
TI  - Inauguration of radiotherapy as a new scientific speciality by Leopold Freund 100
      years ago.
AB  - There is an increasing acceptance and knowledge of the fact that the inauguration
      of radiotherapy as a new scientific speciality was performed by Leopold Freund
      100 years ago. With a clear and logical rationale, Freund provided the first
      scientific proof of the biological effectiveness of X-rays on a 5-year-old
      patient and performed the world's first successful treatment with X-rays. Before
      Freund's historical experimental treatments, which started in Vienna on November
      24th, 1896, there were several suggestions and attempts at the therapeutic use of
      X-rays, however none of these mostly one-of-a-kind attempts was successful, and
      there was no scientific proof of a therapeutic effectiveness of X-rays in these
      previous experiments.

PMID- 9155069
TI  - On the controversies surrounding the origins of radiation therapy.
AB  - In this study the authors analyze the documentation regarding the earliest known
      X-ray treatments with the objective of identifying the true origin of radiation
      therapy. The four most often quoted events, including X-ray treatments allegedly
      performed in 1896 are analyzed in the light of available published reports. From
      this it is concluded that Despeignes of Lyon, who in July of 1896 irradiated a
      patient with cancer of the stomach, is in all likelihood the first person to
      perform documented radiation therapy treatments with a scientific and logical
      basis.

PMID- 9155070
TI  - Primary chemotherapy and preoperative irradiation for patients with stage II
      larger than 3 cm or locally advanced non-inflammatory breast cancer.
AB  - BACKGROUND AND PURPOSE: To evaluate possibility of breast-conserving therapy and
      outcome for patients with locally advanced non-inflammatory breast cancer (LABC)
      and stage II >3 cm in diameter after primary chemotherapy (CT) followed by
      external preoperative irradiation (RT). MATERIALS AND METHODS: Between 1982 and
      1990, 147 patients were treated by four courses of induction CT (doxorubicin,
      vincristine, cyclophosphamide, 5-fluorouracil) followed by preoperative RT (45 Gy
      to the breast and nodal areas) and a fifth course of CT. Three different loco
      regional approaches were proposed depending on tumour characteristics and tumour
      response. After completion of local therapy, all patients received a sixth course
      of CT and a maintenance adjuvant CT regimen without anthracycline. RESULTS:
      Mastectomy and axillary dissection were performed in 52 patients, and
      conservative treatment in 95 patients (48 achieved complete remission and
      received additional radiation boost to initial tumour bed; 47 had a residual mass
      < or =3 cm in diameter and were treated by wide excision and axillary dissection
      followed by a boost to the excision site. Ten-year actuarial loco-regional
      failure rate was 20% after RT alone, 23% after wide excision and RT and 6% after
      mastectomy (P = 0.85). After multivariate analysis, possibility of breast
      conserving therapy was related to initial tumour size. Ten-year overall survival
      rate was 66%; it was not influenced by local treatment (conservative vs. non
      conservative local treatment, P = 0.89). However, local failure significantly
      decreased overall survival (P < 0.0001). After multivariate analysis, tumour
      response after induction CT and clinical stage had a significant impact on
      survival. CONCLUSIONS: The present data indicate that induction CT followed by
      preoperative RT may permit the selection of some patients with LABC or stage II
      >3 cm for conservative treatment. The impact of this treatment modality on long
      term survival remains to be established.

PMID- 9155071
TI  - Clinical target volume localization using conventional methods (anatomy and
      palpation) and ultrasonography in early breast cancer post-operative external
      irradiation.
AB  - PURPOSE: To evaluate the accuracy of three methods, anatomy (A), palpation (P)
      and ultrasounds (US) in localizing the clinical target volume (CTV) in patients
      (pts) with early breast cancer (EBC) undergoing breast external irradiation as
      part of conservation therapy. MATERIAL AND METHODS: One hundred consecutive pts
      with EBC (T(is) 1%, T1 78%, T2 21%, N- 68%, N+ 32%), treated with conservation
      surgery and breast irradiation with opposed tangential portals, were
      prospectively analyzed. Anatomically, palpatory or ultrasound defined field
      borders for CTV localizations were determined in the same position thanks to the
      utilization of a vacuum-formed cellulose acetate immobilization cast, removed
      during CTV definitions. RESULTS: P and US CTV localizations have been found to
      coincide on the four margins (superior, inferior, medial, lateral) in only 1/100
      pts, while no pt showed identical A and US CTV localizations. Only 31/397 (8%)
      field measurements with A, and 98/395 (25%) with P corresponded to US border
      definition. If mean and median values of each field border were considered, the
      CTV was generally overestimated with P appearing more accurate than A in a gross
      definition of the target (P < 0.01). However, a geographical miss of at least one
      field border of CTV occurred in 55% of pts with A and in 36% of pts with P. The
      most critical margin to be defined with conventional methods was the superior
      one: an underestimation of the cranial border of CTV with A was observed in 51%
      and with P in 22% of pts (22% and 8%, respectively, when an underestimation by
      more than 1.5 cm was considered). When pre-menopausal and peri/post-menopausal
      groups of pts were separately analyzed, conventional methods were highly
      inaccurate to define the superior border in younger pts, in which a geographical
      miss was noted with A in 62% and with P in 35% of cases (P < 0.05). When an
      underestimation of more than 1.5 cm was evaluated, these values were reduced to
      33% and 12%, respectively (P = 0.02). Also, in the subgroup of pre-menopausal
      patients the CTV defined by palpatory reference lines appeared to be more
      accurate than A-method (P < 0.01). CONCLUSIONS: Conventional methods frequently
      appear inadequate to localize residual mammary gland in EBC post-operative
      external irradiation. This analysis evidentiates the inaccuracy of empirical CTV
      definition, and suggests that palpation or anatomical reference borders should be
      critically used and that state of art imaging methods should be included in
      treatment planning, particularly in pre-menopausal pts. If economical or
      individual variables have to be taken into account, palpation might be considered
      in post-menopausal women.

PMID- 9155072
TI  - CT planning of boost irradiation in radiotherapy of breast cancer after
      conservative surgery.
AB  - BACKGROUND AND PURPOSE: A study was performed to compare the accuracy of clinical
      treatment set-up and CT planning of boost irradiation in radiotherapy of breast
      cancer. MATERIAL AND METHODS: Between September 1993 and October 1994, 45 women
      who underwent breast conserving surgery and irradiation containing a boost to the
      tumour bed were investigated. Prospective evaluation of CT planning of the boost
      was carried out. The target volume/boost field, electron energy and treatment set
      up had been defined on the basis of clinical examination, initial and
      postsurgical mammograms by one radiotherapist. Next, a planning CT was performed
      in treatment position and a CT-based treatment plan was calculated according to a
      target volume defined by another radiotherapist. The clinical treatment set-up
      was imported into our computer planning system and the resulting isodose plots
      were compared with those from CT planning and reviewed critically. RESULTS: The
      clinically defined treatment set-up had to be modified in 80% of the patients.
      Most discrepancies observed were related to the size of the boost field itself
      and the chosen electron energy. Minor changes had to be made with respect to
      angle of table and gantry. CONCLUSIONS: Critical review of the isodose plots from
      both methods showed clear advantages for CT planning. Guidelines for target
      definition in CT planning of boost irradiation and subgroups of patients
      benefiting from this technique are described.

PMID- 9155073
TI  - Accuracy of two- and three-dimensional photon dose calculation for tangential
      irradiation of the breast.
AB  - Two cubic-shaped phantoms of water equivalent (WE) material, one homogeneous and
      one with a lung substitute were used to simulate an intact breast. They were
      irradiated with a constant dose using an isocentric tangential field of 6- and 18
      MV photons, respectively. The absorbed dose was measured at the isocentre for a
      range of the lateral distances of the isocentre from the edge of the phantoms.
      Four currently available treatment planning systems (TPS), two with a 2
      dimensional (2-D) and two with a 3-dimensional (3-D) algorithm were used to
      calculate the dose at same points in each phantom. A comparison of the results
      showed that for the homogeneous phantom, the 2-D algorithms over-estimated the
      dose by up to 10% for 6-MV photons at an isocentre depth of 1 cm laterally below
      the surface and 3.6% for 18-MV photons at 2 cm below the surface. For the 3-D
      algorithms, agreement with measurement was within +/-3% at all lateral isocentre
      depths for both energies. For the inhomogeneous phantom, as expected, the
      differences were generally greater as all 4 TPS ignore electron transport and
      photon scatter from heterogeneities. Agreement with measurement generally
      improved with increasing lateral depth of the isocentre below the surface.
      Calculations using an anatomical breast phantom showed that when changing from a
      2-D to a 3-D algorithm, differences of 5-10% between the prescribed dose and the
      dose delivered to the patient can be expected, depending on the algorithm used,
      the photon energy and the lateral depth of the dose reference point below the
      skin.

PMID- 9155074
TI  - Dosimetric evaluation of compensation in radiotherapy of the breast: MLC
      intensity modulation and physical compensators.
AB  - BACKGROUND AND PURPOSE: Electronic portal images may be used to design the
      compensation required to maximise dose uniformity in the breast from opposed
      tangential beams. MATERIALS AND METHODS: Four methods of implementing the desired
      compensation have been studied: a simple wedge, a physical compensator in
      conjunction with a wedge; one open field plus four shaped multi-leaf-collimated
      (MLC) fields, and one wedged field in conjunction with three shaped MLC fields.
      Evaluation was performed using thermoluminescent dosimeters (TLDs) placed inside
      a phantom which was designed to mimic the human breast. The measured results are
      compared with both the prediction of the in-house compensation design software
      and with the dose predicted by the GE Target II planning system. The implications
      of each method for the time taken to plan and deliver treatment were analysed.
      RESULTS: The dose inhomogeneity, as measured at seven points in the central plane
      was greatest for the simple wedge (root mean square (rms) = 4.5%) compared to an
      open field plus four shaped MLC fields (rms = 2.2%), a wedged field plus three
      shaped MLC fields (rms = 3.3%), and the physical compensator (rms = 2.4%). The
      times required to plan and prepare these treatments varied considerably. The
      standard wedged treatment required under 15 min; both MLC-based and the physical
      compensator treatments required approximately 50 min. Differences of treatment
      delivery times were up to 8 min. CONCLUSIONS: These results indicate that the
      dose inhomogeneity can be reduced by beam intensity modulation designed using
      EPIDs.

PMID- 9155075
TI  - Measurement of the peripheral dose for the tangential breast treatment technique
      with Co-60 gamma radiation and high energy X-rays.
AB  - BACKGROUND AND PURPOSE: Published data to estimate the dose outside the primary
      beam, i.e. the peripheral dose (PD), are only valid for perpendicularly incident
      beams. In radiotherapy of breast cancer patients often a tangential beam
      technique is used, for which the published PD data cannot be applied. MATERIAL
      AND METHODS: Measurements were made in a water phantom for three sizes of a
      breast phantom, representing a small, medium, and large breast. Open and wedged
      beams were used. Photon energies were 60Co gamma radiation and 6- to 25-MV X
      rays. The PD was also determined in a humanoid phantom. To check the validity of
      the phantom measurements, the PD was measured in 50 patients referred to this
      institute for radiotherapy of the breast. RESULTS: The mean of the ratios of the
      measured to the estimated PD was 1.12, with a standard deviation of 26%. The data
      set was used to estimate the fetal dose for a 'standard' patient, as a function
      of stage of pregnancy. CONCLUSIONS: The measurements have resulted in a data set,
      which enables calculation of the peripheral dose for the tangential beam
      technique. The accuracy is considered to be adequate for risk assessment.

PMID- 9155076
TI  - Comparison of measured and calculated peripheral doses in patients undergoing
      radiation therapy.
AB  - BACKGROUND AND PURPOSE: Many papers have been published on the measurement for
      specific treatment machines and/or techniques of the dose to points outside the
      primary beam, often called the peripheral dose (PD). Most papers concern
      measurements in phantoms. We report on the results of a comparison of estimates
      of the PD, based on these phantom measurements, with PDs measured on patients.
      MATERIAL AND METHODS: A special holder with thermoluminescent dosimeters was
      placed against the perineum of patients referred to our institute for radiation
      therapy. The measured dose was then compared with the dose calculated on the
      basis of published PD data. RESULTS: For all measurements together, the
      calculated values exceeded the measured PDs by about 9%, with a standard
      deviation of 35%. The correlation varied between specific subgroups but the
      difference between measurement and calculation did not exceed 50%. CONCLUSIONS:
      We conclude that published PD data can be used to accurately predict the
      peripheral dose in the clinical situation.

PMID- 9155077
TI  - Comparison between dose values specified at the ICRU reference point and the mean
      dose to the planning target volume.
AB  - BACKGROUND AND PURPOSE: To compare dose values specified at the reference point,
      as recommended by the International Commission on Radiation Units and
      Measurements, ICRU, and the mean dose to the planning target volume, PTV.
      MATERIAL AND METHODS: CT-based dose calculations were performed with a 3-D
      treatment planning system for 6 series of patients treated for bladder, brain,
      breast, lung, oropharynx and parotid gland tumour. All patients were arbitrarily
      chosen from a set of previously treated patients irradiated with a two- or three
      field technique using customised blocks. Appropriate wedge angles and beam
      weights were chosen to make the dose distribution as homogeneous as possible.
      RESULTS: The dose at the ICRU reference point was generally higher than the mean
      dose to the PTV. The difference between the ICRU reference dose and the mean dose
      to the PTV for an individual patient was less than 3% in 88% of cases and less
      than 2% in 72% of the cases. The differences were larger in those patients where
      the dose distribution is significantly influenced by the presence of lungs or air
      gaps. For each series of patients the mean difference between the ICRU reference
      dose and the mean dose to the PTV was calculated. The difference between these
      two values never exceeded 2%. Because not all planning systems are able to
      calculate the mean dose to the PTV, the concept of the mean central dose, the
      mean of the dose values at the centre of the PTV in each CT slice, has been
      introduced. The mean central dose was also calculated for the same patients and
      was closer to the mean dose to the PTV than the ICRU reference dose. CONCLUSION:
      The mean dose to the PTV is well estimated by either the ICRU reference dose or
      the mean central dose for a variety of treatment techniques for common types of
      cancer.

PMID- 9155078
TI  - Orthovoltage applicator design: its effect on a transmission monitor chamber.
AB  - In the Pantak DXT300, the applicators are mounted immediately below a
      transmission monitor chamber. Changing the metals used in applicator construction
      can cause variations of up to 22% in calibration factor (cGy MU(-1)) and apparent
      dose rate (MU min(-1)), but has no effect on radiation dose rate (cGy min(-1)).
      The results are consistent with being caused by backscatter from the applicator
      to the monitor chamber.

PMID- 9155079
TI  - Surface and percentage depth doses for secondary blocking using a multileaf
      collimator and cerrobend-alloy blocks.
AB  - Percentage depth doses from the surface to a depth of 30 cm have been measured
      for a number of square fields using 6 MV and 15 MV X-rays as part of the
      commissioning procedure for a commercially available MLC. Factors such as
      changing SSD, presence of a secondary blocking tray in the beam, and radiation
      transmission between the MLC leaves were investigated.

PMID- 9155080
TI  - Dose perturbations due to in vivo dosimetry with diodes.
AB  - In vivo dosimetry performed with semiconductor detectors is a reliable method for
      patient dose control. The purpose of this study is to evaluate the perturbations
      introduced in the patient's absorbed dose distribution by three types of
      commercially available diodes (Isorad, Sun Nuclear Corp.; model 114200, 114300
      and 114400) from the same company and to present possible solutions for
      minimizing this side-effect.

PMID- 9155081
TI  - Semi-conductor detectors in output factor measurements.
AB  - BACKGROUND AND PURPOSE: Output factors are generally measured with cylindrical
      ionization chambers. It was investigated if Si-diodes of p-type instead could be
      used. The advantage would be the small detector size and the robust construction
      of the detector. MATERIALS AND METHODS: Two types of diodes were studied, one
      with a shielding layer of tungsten specially made to reduce the excess response
      for scattered photons and one standard diode without any extra shielding. The
      measurements were performed at accelerating potentials between 4 and 50 MV and
      beam sizes between 4 cm x 4 cm and 40 cm x 40 cm. RESULTS: The results showed
      that both types of diodes are suitable for measurements of head scatter factors
      in mini-phantoms. However, the diodes were found inappropriate for measurement of
      output factors for large fields in extended water phantoms. For small fields (<10
      cm x 10 cm) a small detector is advantageous and no errors due to the scatter
      contribution were seen. CONCLUSIONS: An cylindrical ionization chamber is the
      best choice for output factor measurements in extended water phantoms for large
      field sizes while diodes are an alternative in small fields. There were
      negligible differences between the detectors in head scatter measurements in mini
      phantoms.

PMID- 9155082
TI  - An independent check of treatment plan, prescription and dose calculation as a QA
      procedure.
AB  - In many radiotherapy centres where planning for external beam treatments is
      performed by radiation therapists, the treatment sheet and its calculations are
      independently checked by staff from a different educational background, typically
      a radiotherapy physicist. The benefits of this practice were evaluated in a
      radiotherapy department with two linear accelerators, one combined superficial
      orthovoltage unit and one telecaesium unit. Within the 19 months of the
      investigation period, 2328 checks were performed on the treatment sheets of 1579
      patients. In six cases, errors in excess of 5% were detected, which if
      uncorrected, could potentially have affected local tumour control or caused
      normal tissue complications. It was found that an independent check of treatment
      sheets assists in keeping these errors as low as can be achievable in clinical
      practice, and suggests that treatment sheet checking and in vivo dosimetry play a
      complementary role in this aim. Independent treatment sheet checking is an
      important quality assurance (QA) activity, with additional advantages such as
      improved communication in the department, education of staff and in vivo
      dosimetry targeting. Therefore the advantages of the procedure seem to outweigh
      the additional workload of approximately 0.3 full-time staff per 1000 patients
      per year.

PMID- 9155083
TI  - RBE variation as a function of depth in the 200-MeV proton beam produced at the
      National Accelerator Centre in Faure (South Africa).
AB  - BACKGROUND AND PURPOSE: Thorough knowledge of the RBE of clinical proton beams is
      indispensable for exploiting their full ballistic advantage. Therefore, the RBE
      of the 200-MeV clinical proton beam produced at the National Accelerator Centre
      of Faure (South Africa) was measured at different critical points of the depth
      dose distribution. MATERIAL AND METHODS: RBEs were determined at the initial
      plateau of the unmodulated and modulated beam (depth in Perspex = 43.5 mm), and
      at the beginning, middle and end of a 7-cm spread-out Bragg peak (SOBP) (depths
      in Perspex = 144.5, 165.5 and 191.5 mm, respectively). The biological system was
      the regeneration of intestinal crypts in mice after irradiation with a single
      fraction. RESULTS: Using 60Co gamma-rays as the reference, the RBE values (for a
      gamma-dose of 14.38 Gy corresponding to 10 regenerated crypts) were found equal
      to 1.16 +/- 0.04, 1.10 +/- 0.03, 1.18 +/- 0.04, 1.12 +/- 0.03 and 1.23 +/- 0.03,
      respectively. At all depths, RBEs were found to increase slightly (about 4%) with
      decreasing dose, in the investigated dose range (12-17 Gy). No significant RBE
      variation with depth was observed, although RBEs in the SOBP were found to
      average a higher value (1.18 +/- 0.06) than in the entrance plateau (1.13 +/-
      0.04). CONCLUSION: An RBE value slightly larger than the current value of 1.10
      should be adopted for clinical application with a 200-MeV proton beam.

PMID- 9155084
TI  - The pocket linac: a hand-held device for finding IEC collimator angles and
      independent jaw settings.
AB  - The final stage in the production of a radiotherapy treatment plan must always be
      an independent check that the linear accelerator settings given on the plan do in
      fact deliver the required dose distribution. A tool is described that enables
      rapid checking of diaphragm settings in relation to the patient.

PMID- 9155085
TI  - The ICRU 38, a need for a new edition.

PMID- 9155086
TI  - H.D. Kogelnik's article on Leopold Freund.

PMID- 9155087
TI  - Mapping of exposed surfaces of the nicotinic acetylcholine receptor by
      identification of iodinated tyrosine residues.
AB  - Here we report on the use of iodination of the membrane-bound nicotinic
      acetylcholine receptor (nAChR) from Torpedo californica electric tissue in order
      to define surface-exposed portions of the receptor molecule. Membrane-bound nAChR
      was 125I-iodinated using the oxidation agent Iodo-Gen. The iodinated subunits
      were separated by preparative gel electrophoresis, desalted, and cleaved with
      trypsin. The resulting peptides were separated by reverse-phase HPLC and the
      radioactive peptides were identified by mass spectrometry and protein sequencing.
      For the delta-subunit, we identified five iodinated peptides containing the
      tyrosine residues deltaTyr17, deltaTyr74, deltaTyr365, deltaTyr372, and
      deltaTyr428. The surface exposition of these amino acids is in agreement with the
      four-transmembrane-segment model (4TM model) of the nAChR, but the assignment to
      the intra- or extracellular surface is doubtful. According to this model, the N
      terminal portion of the receptor subunits including the iodinated residues
      deltaTyr17 and deltaTyr74 is extracellular and deltaTyr372 as a site of tyrosine
      phosphorylation is located on the cytoplasmic side. But since this latter residue
      is among the first to be iodinated using an immobilized iodination agent, its
      true position with respect to the membrane bilayer is not clear.

PMID- 9155088
TI  - Purification and characterization of cathepsin D from normal human breast tissue.
AB  - The lysosomal aspartyl protease cathepsin D is present in most mammalian cells
      and is active in the catabolism of intracellular and endocytosed proteins. It
      appears to be overexpressed and abnormally secreted in breast cancer cells, and
      may contribute to the process of tumor metastasis. In the present study,
      cathepsin D was purified 4500-fold from normal human breast tissue using
      pepstatin-agarose, DEAE Sephadex, and Sephadex G-75 chromatography. The resulting
      enzyme on SDS-PAGE contained five protein bands (47, 31, 29, 13, and 12kDa) which
      were all immunoreactive on western blot analysis using anti-cathepsin D
      polyclonal antibodies. The isoform profile of purified cathepsin D consisted of
      three major peaks at approximate pI 7.3, 6.8, and 6.3, and a broad area of lower
      activity between pI of 5.0 and 2.0. The purified enzyme had a broad pH optimum
      centered around pH 3.3. Lectin blotting indicated that cathepsin D is a
      glycoprotein which is recognized by Galanthus nivalis agglutinin and concanavalin
      A, suggesting the presence of mannose residues. However, Sambucus nigra
      agglutinin, Tetragonolobus purpureas agglutinin, Triticum vulgaris agglutinin,
      and Erythrina cristagalli agglutinin failed to recognize cathepsin D, suggesting
      a lack of lectin-available sialic acid, fucose, N-acetylglucosamine, and
      galactose residues, respectively.

PMID- 9155089
TI  - Chemical modification of lyophilized proteins in nonaqueous environments.
AB  - Lyophilized proteins were reacted in vacuo with a volatile reagent or dispersed
      in octane and reacted with dissolved reagent. Three novel derivatives were formed
      with iodomethane: (a) quaternized trimethyl amino groups, (b) N1,N3
      dimethylimidazolium cation, and (c) phenolic O-methyl ether. Acid anhydrides
      acylated amino groups and formed mixed anhydrides with side-chain carboxyl
      groups. Under nonaqueous conditions it was observed that: (i) The same
      derivatives are formed as under aqueous conditions. (ii) Hydrolytic breakdown of
      protein is prevented. (iii) Less reagent is required. (iv) Unreacted reagent can
      be recovered. (v) Water-labile derivatives can be isolated as stable
      intermediates. (vi) The yield of a derivatized functional group was directly
      related to its pK(a), its surface exposure, and the pH of the solution from which
      the protein was lyophilized. (vii) The physicochemical factors governing the
      reactivity of protein functional groups in nonaqueous environments appear to
      reflect the protein solution structure prior to lyophilization.

PMID- 9155090
TI  - Trypsin inhibitor polymorphism: multigene family expression and posttranslational
      modification.
AB  - Trypsin inhibitors from winter pea seeds (c.v. Frilene) have been purified and
      shown to consist of six protease inhibitors (PSTI I, II, III, IVa, IVb, and V).
      Based on amino acid composition, molecular mass, and N-terminal sequence, the six
      inhibitors are closely related to one another and belong to the Bowman-Birk
      family of inhibitors. To define the relations among them, molecular mass and
      amino acid composition of peptides obtained from digestion with trypsin were
      determined. The sequence and the biosynthetic mechanism of the isoform formation
      have been partially resolved for four major isoforms. Two isoinhibitor forms
      (PSTI IVa, IVb) in pea seeds are due to expression of two distinct genes; PSTI
      IVa has four amino acid replacements when its sequence is compared with the
      sequence of PSTI IVb. Two others (PSTI I, II) result from posttranslational
      proteolytic cleavage of nine C-terminal residues of forms PSTI IVa and IVb,
      respectively.

PMID- 9155091
TI  - Qualitative analysis of the carbohydrate composition of apolipoprotein H.
AB  - The specific binding of digoxigenin-labeled lectins to carbohydrate moieties is
      used to characterize the carbohydrate chains bound to apolipoprotein H. Our
      results show that apolipoprotein H is rich in sialic acid linked alpha(2-6) to
      galactose or N-acetylgalactosamine. Sialic acid is not alpha(2-3)-linked to
      galactose. Galactose is beta(1-4)-linked to N-acetylglucosamine and beta(1-3)
      linked to N-acetylgalactosamine. High-mannose N-glycan chains are barely
      detectable. After N-glycosidase F treatment the molecular weight is substantially
      reduced. The main band is 32,500 daltons. Carbohydrate O-linked chains, which are
      mainly represented by sialic acid, are alpha(2-6)-linked to galactose or N
      acetylgalactosamine. Galactose is also organized in O-linked chains and it is
      beta(1-4)-linked to N-acetylglucosamine and beta(1-3)-linked to
      acetylgalactosamine. Biochemical analysis of carbohydrate structures reveals that
      no specific carbohydrate complex is bound to a single isoform.

PMID- 9155092
TI  - Changes in conformation and stability upon formation of complexes of
      erythropoietin (EPO) and soluble EPO receptor.
AB  - Erythropoietin (EPO) is a glycoprotein hormone which belongs to the four-helical
      bundle cytokine family and regulates the level of circulating red blood cells.
      The EPO receptor (EPOR) belongs to the cytokine-receptor family of proteins.
      While many of the downstream events following receptor/ligand interaction have
      been defined, both ligand-induced receptor dimerization and conformational
      changes induced by binding have been implicated as the initial step in signal
      transduction. In a recent paper [Philo et al. (1996), Biochemistry 38, 1681-1691]
      we described the formation of both 1:1 and 2:1 EPOR/EPO complexes. In this paper,
      we examine changes in protein conformation and stability resulting from the
      formation of both 1:1 and 2:1 complexes of the soluble extracellular domain of
      EPOR and the recombinant EPO derived from either Chinese hamster ovary cells or
      from Escherichia coli cells. Occupation of the first binding site results in a
      slight conformational change that is apparent in both the far- and near-UV
      circular dichroism spectra. Formation of the 2:1 complex results in an even
      greater change in conformation which involves the local environment of one or
      more aromatic amino acids, accompanied perhaps by a small increase in helical
      content of the complex. This change in local conformation could occur in the EPO
      molecule, in the EPOR, in both EPOR molecules due to dimerization, or in all
      molecules in the trimer. The 1:1 complex exhibits increased stability to thermal
      induced denaturation relative to the individual protein component; indeed, the E.
      coli-derived (nonglycosylated) EPO stays folded in the complex at temperatures
      where the EPO alone would have unfolded and precipitated. Glycosylation of the
      receptor increases the reversibility of thermal denaturation, but does not affect
      the temperature at which this unfolding reaction occurs.

PMID- 9155093
TI  - Minimal functional unit of lactate dehydrogenase.
AB  - The tetrameric heart isozyme of lactate dehydrogenase (H4) is modified by p
      chloromercuribenzoate (PCMB) to produce the inactive tetramer (H4) and then
      hybridized with native tetrameric muscle isozyme (M4). The hybrid mixture (M4,
      H'M3, H2'M2, H3'M, and H4') was isolated by polyacrylamide gel electrophoresis
      (PAGE) and then stained for enzyme activity and with Coomassie brilliant blue.
      Only three bands were found on the gels in either case. The hybrid enzymes (H'M3
      and H2'M2) as isolated by PAGE have half the specific activity of the native
      muscle enzyme. The electrophoresis properties of H'M3 are very similar to those
      of HM3, while the electrophoresis properties of H2'M2 are very similar to those
      of H2M2. The above results strongly suggest that the tetramer having enzymatic
      activity contains at least two native subunits, and the di-subunit in the
      tetrameric enzyme is the minimal functional unit.

PMID- 9155095
TI  - Additional information on packs.

PMID- 9155094
TI  - Site-directed mutagenesis in basic amino acid residues of Saccharomyces
      cerevisiae phosphoenolpyruvate carboxykinase.
AB  - Mutant Arg76Gln and Lys290Gln Saccharomyces cerevisiae phosphoenolpyruvate
      carboxykinases have been prepared and analyzed. No alteration in the apparent
      kinetic constants were detected for the Arg76Gln mutant enzyme, while the
      Lys290Gln mutant showed a 12-fold decrease in V(max)/K(m)ADP. These results
      indicate that Arg76 is not involved in CO2 binding, but support the hypothesis
      that the binding of this substrate induces a conformational change that protects
      the region around Arg76 from trypsin action [Herrera et al. (1993) J. Protein
      Chem. 12, 413-418]. These findings also indicate that Lys290, a highly reactive
      residue against pyrydoxal phosphate [Bazaes et al. (1995), FEBS Lett. 360, 207
      210], does not perform an essential function for the enzyme activity.

PMID- 9155096
TI  - Spinal cord injury questions.

PMID- 9155097
TI  - Neurosurgery in Rwanda during a United Nations peace-keeping mission.
AB  - An analysis of the neurosurgical component of the medical support provided by a
      United Nations peace-keeping mission in Rwanda is presented. The Australian
      Defence Force contingent provided medical support to the United Nations and the
      civilian population. Eight hundred thirty-eight procedures were performed during
      12 months. A wide range of surgery was encompassed, with neurosurgery accounting
      for 17 (2%) of the total operations: compound depressed fractured skull, 5;
      intracranial pressure monitor, 2; burr holes for acute head injury and chronic
      subdural hematoma, 2; skull osteomyelitis debridement, 1; rib-graft cranioplasty,
      2; scalp rotation flap, 1; congenital myelomeningocele, 2; occipital meningocele,
      1; craniofacial approach to Le Fort III fracture, 1. A broad range of
      neurosurgical procedures have been performed. The overall numbers of
      neurosurgical operations were small, but they were successfully performed by
      general surgeons. Familiarity with neurosurgery is necessary in predeployment
      training of military surgeons working in a remote location with limited
      resources.

PMID- 9155098
TI  - The University Integrated Automated Information System at the Uniformed Services
      University of the Health Sciences.
AB  - The Integrated Automation System put into place at the University Services
      University of the Health Sciences has been said to be 5 years ahead of those
      employing the most advanced comparable configurations. This automated data
      processing creation was accomplished without augmentation of manpower or funding.
      A brief history of this development and some of its features are presented.

PMID- 9155099
TI  - Ciguatera fish poisoning.
AB  - Ciguatera fish poisoning is the most common form of toxin-related food poisoning
      in the United States. Originating from dinoflagellates living on coral reefs, it
      is spread up the food and affects humans who ingest the ciguatoxic fish.
      Ciguatera is primarily endemic in tropical regions of the world. It is a self
      limiting disease that presents with characteristic gastrointestinal,
      neurological, and cardiovascular symptoms. Recent advances in testing procedures
      and symptom recognition has improved ciguatoxin identification and clinical
      management. However, there is still a need for better diagnostic, preventive, and
      reporting protocols to more accurately study and understand this diverse and
      temporarily debilitating clinical syndrome.

PMID- 9155100
TI  - Maxillo-mandibular fixation trends in the United States.
AB  - Questionnaires were sent to directors of the 118 oral and maxillofacial surgery
      training programs in the United States and its territories to survey current
      trends and recent experience with maxillo-mandibular fixation (MMF). Eighty-eight
      percent of the respondents indicated that it was customary to keep wire cutters
      at the bedsides of hospitalized patients who were in MMF, and 49% discharged
      patients in MMF with wire cutters. The respondents were aware of 17 inpatients
      and 5 outpatients in their programs who had required emergency release from MMF
      during the previous 5 years. Emergent MMF release is a rare event. The
      availability of wire cutters at the hospital bed or issuance of wire cutters to
      outpatients in MMF should be based on a case-by-case consideration of the
      procedure performed, postoperative bleeding, vomiting potential, edema, airway
      integrity, patient dexterity, and patient compliance.

PMID- 9155101
TI  - The achievements of William Crawford Gorgas.
AB  - From an obscure frontier surgeon George Crawford Gorgas became internationally
      acclaimed as a preventive medicine genius. By his initiative in translating the
      known scientific facts made possible during the blossoming of bacteriology, he
      performed service not only in the United States but in Cuba, Central and South
      America, South Africa, and Eastern Europe. He fought for 10 years successfully
      against yellow fever, malaria, and other diseases during the construction of the
      Panama Canal, and continued triumphs against disease in other world situations.
      This is a rather concise account emphasizing his continued devotion and
      dedication as a humanitarian. He fashioned the Army Medical Department into an
      efficient machine as Surgeon General, and following his amazing military career
      of over 38 years, made further contributions in preventive medicine with the
      Rockefeller Foundation.

PMID- 9155102
TI  - The Tripler Army Medical Center LEAN Program: a healthy lifestyle model for the
      treatment of obesity.
AB  - This paper provides an overview of the Tripler Army Medical Center LEAN Program
      for the treatment of obesity, hypercholesterolemia, and essential hypertension.
      The LEAN Program, a multi-disciplinary prevention program, emphasizes healthy
      Lifestyles, Exercise and Emotions, Attitudes, and Nutrition for active duty
      service members. The treatment model offers a medically healthy, emotionally
      safe, and reasonable, low-intensity exercise program to facilitate weight loss.
      We will discuss the philosophy behind the LEAN Program and the major components.
      Thereafter, we will briefly discuss the preliminary results.

PMID- 9155103
TI  - Sanitation of the liberated territories in Croatia after the Storm campaign: the
      example of Lika-Senj County.
AB  - More than 6,000 km2 of the central and southern areas of the Republic of Croatia
      were liberated by the Storm campaign, August 4 to 7, 1995. On August 8, 1995, the
      Ministry of Health sent expert teams to the newly liberated areas, to ensure the
      basic conditions for the displaced persons to return and live there. To describe
      the public health measures taken we used the examples of Lika-Senj County (3,746
      km2 and 71,215 population). By October 1, 1995, 50 bodies, killed in action, had
      been detected, pathologically and forensically examined, and then buried. Two
      hundred thirty-three mostly elderly and sick persons were admitted to the
      reception center in Gospic; 93 of them returned to their homes, 133 were
      accommodated with their relatives and friends, and 7 were referred for treatment
      (4 of them died). Two hundred ten cattle carcasses were buried using adequate
      sanitation measures, whereas 5,575 sheep, 3,138 head of horned cattle, 298 head
      of hoofed animals, and 300 head of other cattle were caught alive. The procedures
      of disinfection, disinfestation, and deodorization were performed in 720
      apartments, 2 hotels, 3 schools, 1 kindergarten, 1 health care unit, 1 sports
      hall, and 5 shops. The main water pump was cleared of mines and partially
      repaired, whereas some 20 water supply facilities were placed under surveillance.
      Three food depots were found and properly treated. The entire territory was
      closely observed for possible occurrence of infectious disease.

PMID- 9155104
TI  - Tuberculosis skin test conversion among health care workers at a military medical
      center.
AB  - Health care workers (HCW) are at risk of occupationally acquiring Mycobacterium
      tuberculosis (TB) infection. The Centers for Disease Control and Prevention has
      published guidelines for health care facilities to protect HCW. One of the
      recommended elements is TB infection surveillance among HCW using purified
      protein derivative (PPD) skin testing and analysis of the data by occupational
      group and work location to determine areas of increased risk of infection. At the
      military medical center (MMC) we studied, occupational groups with statistically
      significant (p < 0.05) above-average PPD conversion risk (> 1.1%/year) included
      respiratory therapists (15.6%/year), nursing technicians (2.3%/year), and
      military personnel (1.6%/year). Maintenance and engineering workers (2.6%/year),
      food service workers (2.5%/year), laboratory workers (2.0%/year), custodial
      workers (1.8%/year), and practical nurses (1.7%/year) had above-average, but not
      statistically significant, risk. The fourth floor of the MMC had 39% (21/54) of
      the converters. The surveillance program also uncovered 235 individuals who had
      not completed adequate prophylactic therapy, and a case of active TB in a
      laboratory worker.

PMID- 9155105
TI  - War injuries of the ureter.
AB  - During the 18 months of war in Croatia, from 1991 until 1992, 4,425 wounded
      patients were treated at Clinical Hospital Osijek. Urogenital injuries were
      present in 115 treated patients (2.6%), and among them ureteral injuries were
      present in 11 patients (9.5%). The ureteral injuries were discovered by chance
      during exploratory abdominal surgery performed for other accompanying injuries.
      Ureteroureteral anastomosis was done in three cases. In three cases
      ureterocystoneostomy was performed. Exploration only was performed in three cases
      and nephrectomy was performed in two cases. It is important to emphasize that in
      three cases with contusions of the ureter wall that were not surgically
      reconstructed, the final result was ureteral stenosis. Moreover, in one case the
      final result was complete obliteration of the ureteral lumen.

PMID- 9155106
TI  - Urogenital war injuries.
AB  - Out of 1,350 war casualties treated at the University Hospital Rebro during the
      defensive war in Croatia, 60 (4.4%) injuries of the urogenital tract were
      present. Among these 60 casualties, 51 (85.0%) had multiple injuries, most often
      abdominal and urogenital. These patients were accordingly treated by combined
      urological and surgical teams. Regarding injuries, there were 21 kidney injuries,
      11 ureter (2 patients had bilateral injuries), 7 urinary bladder, 2 urethral, 15
      testicular, and 6 penile injuries subjected to surgical treatment. Nephrectomy
      was performed in 6/21 patients with kidney injuries. Orchiectomy was performed in
      40% of patients with testicular injuries. In the remaining patients with
      urological tract injuries, surgical reconstruction with organ conservation was
      performed.

PMID- 9155107
TI  - Conspiring to succeed: the process of a joint military health care merger.
AB  - Congress has mandated that the military services improve their health care
      systems to improve access, assure high-quality care, provide more choices, and
      contain costs. In response, the Department of Defense established the TRICARE
      system, organizing it geographically into 12 health services regions. This paper
      tracks the efforts of one of those 12--region IV--to plan for this change using
      strategic planning. Region IV's board of governors represents military facilities
      in Mississippi, Florida, Alabama, Tennessee, and Louisiana, including one clinic
      managed by the U.S. Coast Guard, Department of Transportation. Strategic planning
      usually involves people who know each other and work together. Because of the
      joint nature of this effort, the members were unfamiliar with one another and
      with the others' systems. There were also physical distances to overcome. This
      paper documents that unique experience, likened to a "corporate merger," and the
      lessons learned from it.

PMID- 9155108
TI  - A team approach to the treatment of musculoskeletal injuries suffered by Navy
      recruits: a method to decrease attrition and improve quality of care.
AB  - In 1991, musculoskeletal injuries prevented 488 recruits from completing basic
      training at the Naval Recruit Training Command, Great Lakes, Illinois. These
      losses cost the Navy an estimated $5 million. To respond to the large number of
      injured recruits, a multi-disciplinary team was developed in 1992. Along with
      this team, a three-tiered, systematic approach to injuries was implemented. These
      changes were associated with an increase in the recovery rate for injured
      recruits requiring physical therapy, a decrease in the amount of training time
      lost per injury, and fewer total lost training days due to musculoskeletal
      problems. In addition, this new system was associated with a decrease in the
      overall attrition rate for musculoskeletal injuries and a cost savings to the
      Navy of several million dollars per year.

PMID- 9155109
TI  - Mobile surgical teams of Croatian Special Police Forces: analysis of casualties
      during combat.
AB  - The purpose of this article is to present medical results of mobile surgical
      teams (MST) supporting units of Croatian Special Police Forces in three attack
      combat actions. The rate of injury was from 2.0 to 1.3%, Whereas the combat
      mortality rate was between 0.20 and 0.17%. No postoperative mortality occurred.
      Heavy injuries were found in 45% of all injured, among them 57% caused by shell
      fragments. Extremities were involved in 92% of all injuries, whereas 50% were
      injuries of the calf. All the injured were surgically managed by MST at the site
      of deployment or in mobile surgical hospitals and evacuated to general hospitals
      within 12 hours, where 80% of all heavily injured patients underwent additional
      operations with no postoperative mortality. Eight to 36 months after injury, we
      found major functional disability in 2% of all injured. NATO schemes served as a
      basis for the formation of the Croatian war surgical care system with certain
      modifications dictated by specific situations at the beginning of the aggression
      against Croatia. MST of Croatian Special Police Force presented second- and third
      -echelon staged management of the wounded, which was adequate for this type of
      attack combat situation.

PMID- 9155110
TI  - Septic syndrome and septic shock in the wounded treated at the Split Clinical
      Hospital Intensive Care Unit.
AB  - INTRODUCTION: A retrospective study on the occurrence of septic syndrome and
      septic shock, as well as multiorgan failure, in the wounded at the Split Clinical
      Hospital Intensive Care Unit (ICU). PATIENTS AND METHODS: From 1991 to 1995, 257
      wounded persons were treated at the Split Clinical Hospital ICU. Criteria for
      septic syndrome included evident infection, body temperature > 38 degrees C or <
      30.5 degrees C, leukocytosis or leukopenia, thrombocytopenia, as well as
      dysfunction of one organ. The criterion for septic shock was septic syndrome with
      hypotonia. RESULTS: Fifteen patients with septic syndrome and 9 patients with
      septic shock were admitted and treated at the ICU. Septic syndrome developed in
      17 patients and septic shock in 16 patients at the ICU. Acute respiratory
      distress syndrome developed in 16, renal insufficiency in 26, gastrointestinal
      disorders in 6, hepatic disorders in 4, hematologic disorders in 13, and central
      nervous system dysfunction in 17 patients. Twenty-eight percent of patients died
      in septic syndrome, and 74% died in septic shock. CONCLUSION: Septic syndrome and
      septic shock were the most common causes of death in wounded persons treated at
      Split Clinical Hospital ICU. At the earliest phase the main cause of death was
      refractory hypotension, and at the later stage the main cause of death was
      multiorgan failure.

PMID- 9155111
TI  - Systemic sepsis following hemorrhagic shock: alleviation with oral interleukin-6.
AB  - Gut-origin sepsis is a serious medical complication of military injuries
      following hemorrhage. Splanchnic ischemia induces intestinal necrosis leading to
      systemic bacteremia. Rat and mouse models of hemorrhagic shock were used to
      investigate bacterial translocation from the gut. Orally administered
      ameliorative treatments using the cytokine interleukin-6 (IL-6) were able to
      reduce or eliminate sepsis following hemorrhage. To mimic battlefield wounds and
      hemorrhage, anesthetized mice were bled from the femoral artery, held at a mean
      arterial blood pressure of 35 mm Hg for 1 hour, and then resuscitated with shed
      blood and 2-fold volume lactated Ringer's solution. Anesthetized rats were bled
      from the carotid artery at a rate of 15 ml/kg at 1 ml/minute. Bacteriological
      cultures of livers and mesenteric lymph nodes from hemorrhaged animals given
      recombinant IL-6 had significantly fewer colonies per gram of tissue than saline
      fed controls. 125I-labeled IL-6 remained in the gut for up to 6 hours giving
      regional protection, whereas labeled interleukin-2 was disseminated throughout
      the body in the same time. In vivo and vitro studies of IL-6 showed that long
      incubations with high doses of trypsin, chymotrypsin, or intestinal contents were
      necessary to inactivate the bioactivity of this cytokine. Electron microscopy
      showed that epithelial cells from hemorrhaged mice fed saline had sparse or
      missing villi and vacuolated cytoplasm. Epithelial cells from control mice or
      mice hemorrhaged and fed cytokine appeared completely normal. Oral administration
      of IL-6 on the battlefield may be an important treatment for the prevention of
      sepsis following hemorrhage.

PMID- 9155112
TI  - [Natural history of the benign prostatic hyperplasia].

PMID- 9155113
TI  - [Study of the effects of treatment with interferon for the advanced renal cell
      carcinoma based upon the survival rate].
AB  - BACKGROUND: There is no consistent acknowledgment with the effects of the
      prolongation of survival for the advanced renal cell carcinoma (RCC) treated with
      interferon (IFN). Therefore, we tried to study on the effects of such
      prolongation of survival for the advanced RCC through the comparative analysis
      between the patients treated with IFN and the patients treated with other
      treatment modalities in the past years. PATIENTS AND METHODS: We differentiated
      the patients treated with IFN (recurrent patients after nephrectomy as Group I,
      and patients with stage 4B as Group II) from the patients treated with other
      modalities (recurrent patients after nephrectomy as Group III, and patients with
      stage 4B and Group IV). We compared the survival rate between the two groups
      (Groups I vs III, and Groups II vs IV). RESULTS: Regarding the various factors
      affecting prognosis of RCC, no significant difference was observed among these
      groups. 1) There observed a significantly favorable survival rate in the Group I
      compared with the Group III, and the same result was observed in the Group II
      compared with the Group IV. 2) In the patients with performance status (P.S.) 0
      and low grade, there observed a significantly favourable survival rate in the
      Group I compared with the Group III, and the same result was observed in the
      Group II compared with the Group IV. Furthermore, in the patients with low stage,
      the Group I showed a significantly favourable survival rate compared with the
      Group III. 3) In the study on the number of metastatic organs (1, 2 and 3 organs
      or more), there observed a significantly favourable survival rate in the Group I
      compared with the Group III for all numbers of the metastatic organs. The same
      result was observed in the group II compared with the Group IV, except for the
      patient with 3 organs or more. Regarding the operative procedures for the
      metastatic side, the patients who did not receive the operative procedures showed
      a significantly favourable survival rate in the Group I compared with the Group
      III. The same result was observed in the Group II compared with the Group IV. 4)
      As to the survival rate based upon the response rate, only the patients with no
      change (N.C.) showed a significantly favourable survival rate in the Group I
      compared with the Group III. The same result was observed in the Group II
      compared with the Group IV. CONCLUSION: We conclude that the treatment with IFN
      for the advanced RCC would much contribute to the prolongation of the survival in
      comparison with the previous patients who received other treatments.

PMID- 9155114
TI  - [The role of serum soluble interleukin 2 receptor (sIL-2R) levels in patients
      with renal cell carcinoma].
AB  - PURPOSE: The correlation between the serum soluble interleukin-2 receptor (SIL
      2R) levels and clinical stage is demonstrable in a variety of non-Hodgkin
      lymphomas. The prognostic significance of sIL-2R levels in the serum of patients
      with renal cell carcinoma (RCC) was investigated. METHOD: sIL-2R were measured in
      patients with RCC (n=39) and normal control (n=6) by the enzyme immunoassay
      technique. Cases of RCC were classified according to the clinical stage,
      pathological grade and growth type. The IL-2R expression of RCC was evaluated by
      RT-PCR. RESULT: The serum sIL-2R levels of patients with RCC showed significantly
      higher values than those of controls (p < 0.05). The serum sIL-2R levels in RCC
      were closely associated with the stage, grade and growth type of disease. The
      patients with high serum sIL-2R level (> = 1,000 U/L) exhibited a significantly
      poorer prognosis than those with low serum sIL-2R level (<1,000 U/L). The band of
      IL-R was detected only by using the template from the mRNA extracted from a
      resected tumor tissue of the RCC but not from the RCC cell lines. CONCLUSION: It
      was suggested that the measurement of serum sIL-2R levels is useful for
      predicting the prognosis.

PMID- 9155115
TI  - [Significance of transrectal ultrasound and sextant systematic core biopsy for
      performing radical prostatectomy].
AB  - BACKGROUND: To estimate the usefulness of sextant systematic core biopsy or
      transrectal ultrasonography (TURS) for performing radical prostatectomy. METHODS:
      The findings of sextant biopsy and TRUS were compared with 52 step-sectioned
      specimens obtained from radical prostatectomy. RESULTS: In 34 cases with no
      influence of hormonal therapy at the time of TRUS and biopsy, sextant systematic
      core biopsy provided tumor distribution rather precisely. In 33% of the cases who
      had received hormonal therapy, tumor cells were not detected by this sextant
      biopsy series. In these cases, majority of residual cancer existed in transition
      zone, paraurethral or fibromuscular stroma. Six cases showed small adenocarcinoma
      in only one biopsy tip obtained from sextant biopsy, while 4 cases were revealed
      well differentiated adenocarcinoma (Gleason score less than 4) by these core
      biopsies. Comparing with tumor mapping, Gleason score, PSA level and pT stage of
      the radical prostatectomy specimens, these tumors presented as, not clinically
      insignificant, but clinically significant prostate cancer. Playing special
      attention to distraction of normal ultrasound zonal configuration, TRUS detected
      neurovascular invasion with 94.7% sensitivity, 78.3% positive predictive value
      and 90. 9% negative predictive value, while seminal vesicle invasion with 75%
      sensitivity, 50% positive predictive value, 90.9% negative value. CONCLUSION:
      Sextant biopsy tended to underestimate the tumors located in the transition zone,
      paraurethral and fibromuscular lesion. Additional or direct biopsies in
      transition zone are indispensable for accurate diagnosis. Findings of TRUS and
      distribution of positive core biopsy from sextant biopsy enable to extract stage
      C prostate cancer providing negative surgical margin.

PMID- 9155116
TI  - [The background factors influencing loss of sexual intercourse after
      transurethral resection of the prostate (TUR-P)--A study using the Sapporo
      Medical University-Questionnaire].
AB  - BACKGROUND: Sexual dysfunction after transurethral resection of the prostate (TUR
      P) depends on multiple factors including preoperative erectile function itself.
      Using the Sapporo Medical University-questionnaire, we analyzed background
      factors contributing to loss of sexual intercourse after the operation. PATIENTS
      AND METHODS: We sent the self-administered questionnaires to 1,000 patients who
      had received TUR-P. Answers to questions were ranked as scores. Multiple
      regression analysis was used to identify factors significant for loss intercourse
      after TUR-P. RESULTS: The response rate was 63.5%. Patient with incomplete
      answers and those having diseases affecting voiding or sexual function and
      antiandrogen medication were excluded from the study. Leaving 536 patients for
      the final analysis. Scores for sexual desire and erectile function in the
      patients who received TUR-P were lower than those of age-matched healthy males.
      When we divided the patients according to frequency of sexual intercourse before
      and after TUR-P, there was distinct differences in age, scores for sensory
      disturbance, depression, the cooperative value of the sexual partner, sexual
      desire, erectile function, nocturia, residual sensation and urgency between those
      maintaining sexual intercourse and those having lost it. Multiple regression
      analysis using these factors indicated that the scores of erectile function was
      the most significant determinant for maintaining sexual intercourse after TUR-P
      in patients aged from 50 to 69 years, followed by the cooperative value of the
      sexual partner, residual sensation and sensory disturbance. In those 70 old and
      older, the score for erectile function was the most significant determinant,
      followed by the cooperative value of sexual partner. CONCLUSION: Our results
      suggest that, irrespective of age, the cooperation of the patient's sexual
      partner as well as erectile function significantly influence the maintenance of
      sexual intercourse after TUR-P. In addition, voiding condition and psychological
      status after TUR-P may affect the maintenance of sexual intercourse in patients
      in their fifties and sixties.

PMID- 9155117
TI  - [Urethral opening pressure: its clinical significance in prostatic obstruction].
AB  - BACKGROUND: In the evaluation of prostatic obstruction by using the pressure-flow
      study (PFS), we defined intravesical pressure at initiation of voiding as
      urethral opening pressure. This simple parameter could reflect the degree of
      compressive prostatic obstruction to some extent. The aim of this study is to
      analyze if a correlation exsists between clinical signs and urethral opening
      pressure, and if they bear any prognostic value in postoperative outcome of the
      patients. METHODS: We analyzed 46 patients with clinical benign prostatic
      hypertrophy who underwent urodynamic evaluations including PFS. They were divided
      into 2 groups according to their urethral opening pressure. The high opening
      pressure was defined as greater than 70 cm water, which was noted in 24 patients
      (group A). Twenty-two patients had lower opening pressure (group B). Comparison
      of the clinical findings in these patients were reviewed. Medium-filling
      cystometry and PFS were performed transurethrally, by using a microtip transducer
      and rectal balloon. Cystoscopy was performed when possible, wherein we could
      examined the presence or absence of detrusor trabeculation. Transurethral
      prostatectomy was indicated in a total of 26 patients (16 in group A and 10 in
      group B), in whom postoperative clinical findings were analyzed with regard to
      the difference in preoperative urethral opening pressure. The patients who void
      with straining or who void following uninhibited detrusor contraction were
      excluded from this study. RESULTS: International Prostatic Symptoms Score (I-PSS)
      revealed no significant difference in both groups, however, patients in group A
      were often suffering from urge incontinence preoperatively. Significant
      correlation was found among the incidence of detrusor instability, detrusor
      trabeculation and increased opening pressure. In PFS the patients with high
      opening pressure tended to have higher detrusor pressure at maximum flow and
      greater contractile power of the detrusor in voiding. There were no difference in
      Qmax and residual volume both groups. Postoperatively, symptomatic improvement
      was significant in both groups. There was no statistical difference in
      postoperative I-PSS between group A and B. Although 6 patients in group A
      demonstrated poor urinary control at 1 month, only two patients remained
      incontinent at 6 months postoperatively. As to urodynamic findings, the
      difference in PFS were markedly reduced between both groups. No difference was
      noted in postoperative Qmax as well. CONCLUSION: Significant difference was found
      in preoperative objective findings except the flow rate between the patients with
      and without high urethral opening pressure, while no symptomatic difference was
      noted except urege incontinence in both groups. No prognostic value was
      demonstrated in urethral opening pressure, however, poor postoperative urinary
      control was often associated with initial high opening pressure in the short
      term. It was suggested that 1) compensatory detrusor hyperactivity improved
      voiding efficacy in the patients with prostatic obstruction, which was gradually
      normalized after the relief of obstruction, 2) symptomatic improvement was highly
      related to the relative improvement of the obstructive findings on PFS.

PMID- 9155118
TI  - [A case of invasive bladder cancer with Pagetoid skin lesion of the vulva and
      anogenital Paget's disease].
AB  - A 70-year-old female was admitted to our hospital with a complaint of gross
      hematuria for two months. She had a 5 years history of eczematous vulvar skin
      eruption. With the diagnosis of T3N0M0 bladder cancer and anogenital Paget's
      disease, she underwent pelvic exenteration, vulvectomy and reconstruction of the
      vulva. Histopathological examinations and mucin stains revealed anogenital
      Paget's disease and invasive bladder cancer which extended to the clitoral skin
      and formed Pagetoid skin lesion. CEA and cyokeratin staining demonstrated
      identical expression pattern in bladder cancer cells and Paget's cells, which
      suggested both neoplastic cells originated from one progenitor cell.

PMID- 9155119
TI  - [A case of primary osteogenic sarcoma of the kidney].
AB  - Extraosseous osteogenic sarcoma can occur anywhere in the body, but it is
      exceedingly rare to find this malignancy in renal tissue. A review of the
      literature revealed only 16 cases which appeared to be clearly identifiable as
      malignant extraosseous bone-forming sarcoma of the kidney and our report presents
      17th case. The patient was a 67-year-old oriental woman. In March 1994, abdominal
      plain radiographs showed several dense calcifications in the left flank at
      another hospital. In May 1995, a huge tumor appeared in the left upper quadrant,
      so she was admitted to department of Internal Medicine of our institute for
      further examination. As the subsequent abdominal CT scan showed a huge renal
      tumor with accompanying calcifications, she was transferred to department of
      Urology. We diagnosed this tumor to be a huge renal cell carcinoma featuring
      calcifications and performed left nephrectomy. Microscopically, this tumor
      demonstrated predominantly osteoblast-like tumor cells coupled with osteoid and
      bone formation. Its histological appearance was compatible with that of
      osteogenic sarcoma. Bone scan and skeletal radiograph presents to evidence of
      malignancy, which led to our diagnosis of primary osteogenic sarcoma of the left
      kidney. Two months after nephrectomy, we found a large palpable recurrent mass in
      the left upper quadrant of the abdomen. Although two courses of cisplatin were
      then administered, her condition deteriorated until death on October 25, 1995,
      about four months after nephrectomy.

PMID- 9155120
TI  - [Postoperative inflammatory responses to gelatin- and collagen-impregnated Dacron
      grafts and changes of endotoxin].
AB  - Between June, 1993 and January, 1995 a gelatin-sealed knitted Dacron (Gelseal) (g
      G0, n = 7) and a collagen-sealed knitted Dacron graft (Hemashield) (g-H0, n = 8)
      were randomly implanted to 15 patients (pts) for replacement of thoracic aorta.
      We evaluated postoperative inflammatory responses and levels of Toxicolor and
      Endospecy which are the measurements of endotoxin. Five pts in g-G0 and 3 pts in
      g-H0 showed that a body temperature (BT) were above 37.5 degrees C on the 7th
      postoperative day (POD). In three of them (2 in g-G0 and 1 in g-H0), BT above
      37.5 degrees C continued until POD 14 due to the bacterial infection. The other
      causes of elevation of BT were pleural effusion (2), pericardial effusion (1) and
      unknown origin (2). Patients without evidence of infection (n = 12) were divided
      into 2 groups (g-G: pts with Gelseal, n = 5, g-H: pts with Hemashield, n = 7). On
      POD3, postoperative BT in g-H was significantly higher than in g-G. And, on POD7,
      BT in g-G rose up more than in g-H. However, on POD14, BT decreased to the normal
      range in both groups. The values of WBC in g-G were slightly higher than in g-H
      and they became normal after POD7 in both groups. The levels of CRP in g-H were
      higher than in g-G after POD3 and in both groups they were still high on POD14.
      In terms of endotoxin., Toxicolor was already above the normal range from POD1
      and decreased to the normal range after POD14. However, the level of Endospecy
      kept within normal range. In conclusion, Toxicolor-reactive substance elevates by
      using Gelseal and Hemashield. Its substance is not endotoxin. It would not be
      appropriate to consider that endotoxin is an origin of fever between POD7 and 14.

PMID- 9155122
TI  - [The causes and management of ischemic mitral regurgitation].
AB  - Ischemic mitral regurgitation (IMR) is recognized as one of the complications of
      coronary artery disease. The aim of this study is to evaluate the causes and
      surgical management of IMR. From October 1986 to March 1995, 443 of patients
      underwent isolated coronary artery bypass grafting (CABG). In forty-four of the
      patients (9.9%) who underwent isolated CABG, the severity of postoperative IMR
      was reduced by two or more grades by the Sellers index. Hemodynamic parameters of
      these patients included: left ventricle ejection fraction, left ventricle end
      diastolic volume index and left ventricle regional wall motion. They were
      assessed by left ventriculography (LVG). In addition, cardiac index and pulmonary
      artery wedge pressure were assessed by S-G catheterization and mitral annulus
      diameter by ultrasonic echocardiography. Twenty-nine patients experienced an
      increase in IMR severity after CABG, one of whom required mitral valve
      replacement for cardiac failure, and later died due to low output syndrome
      postoperative. On the other hand, fifteen patients experience a reduction in IMR
      severity after CABG. We conclude that the causes of IMR were regional asynergy at
      the site of papillary muscle, mitral annulus dilation and left ventricle
      dilation. Our findings suggest that severe IMR patients required concomitant
      mitral valve surgery with CABG. Patients with mild or moderate IMR patients with
      mitral annulus dilation or regional asynergy at the site of mitral papillary
      muscle may require the same surgery.

PMID- 9155121
TI  - [Effect of extracellular magnesium on reperfused rat heart and intracellular
      calcium concentration of the myocardium].
AB  - Isolated rat hearts were subjected to 30 min global ischemia followed 20 min
      reperfusion with various concentration of Mg2+ Krebs-Henseleit-bicarbonate buffer
      (KHB buffer) (Mg2+:1.2 mM, 2.5 mM, 5 mM, 10 mM) and 20 min reperfusion with
      original KHB buffer (Mg2+:1.2 mM) at 37 degrees C, respectively. Cardiac function
      and the incidence of ventricular arrhythmia were measured during pre-ischemia and
      reperfusion, and intracellular Ca2+ concentration was measured during pre
      ischemia, ischemia and reperfusion period. The hearts reperfused with 1.2 mM Mg2+
      presented a significantly higher frequency of ventricular fibrillation (VF) and
      ventricular tachycardia (VT) than the other groups. Percent recoveries of LVDP
      (Left ventricular developed pressure) at the Mg2+ concentration of 1.2, 2.5, 5,
      10 mM after 40 min reperfusion were 64.3 +/- 5.7%, 108.4 +/- 6.1%, 100.4 +/-
      6.1%, 101.5 +/- 5.5%, respectively. Intracellular Ca2+ concentration of the
      hearts with Mg2+ 1.2 mM revealed 248.9 +/- 15.6% at reperfusion, and that the
      other groups did not increased during reperfusion. These data suggest that
      extracellular Mg2+ inhibits reperfusion arrhythmia and Ca2+ overload during
      reperfusion, and improves cardiac function of reperfused heart.

PMID- 9155123
TI  - [Beneficial effects of continuous hemodiafiltration after cardiac surgery in
      patients with chronic renal failure].
AB  - From December 1993 to June 1996, fourteen patients with chronic renal failure
      (CRF) were underwent cardiac surgery. Thirteen of them had coronary artery bypass
      grafting (CABG) and one patient had aortic valve replacement. We employed
      continuous hemodiafiltration (CHDF) with or without peritoneal dialysis in eleven
      cases in the early postoperative course of open heart surgery. In these cases,
      the usefulness of CHDF were examined. CHDF was started after 16.9 +/- 13.7 hours
      of surgery, and continued for 31.9 +/- 18.0 hours. We adjusted blood flow as 80
      ml/min, perfusate flow of hemofilter as 500 ml/hr, and the activated clotting
      time (ACT) as 150-200 seconds with heparin or nafamostat mesilate. No hemorrhagic
      tendency was observed. Mean serum creatinine level before and after 24 hours of
      CHDF was 5.6 +/- 2.2 and 5.6 +/- 2.1 mg/dl respectively, and it was not elevated.
      The average removal volume was 2,223 +/- 1,256 ml for the first 24 hours, and
      pulmonary wedge pressure was decreased from 9.0 +/- 2.3 to 6.4 +/- 3.0 mmHg (p <
      0.05). However, there was no significant change at cardiac output before and
      after CHDF. Total dose of dopamine and dobutamine were unchanged. No significant
      change were noted at systemic vascular resistance and pulmonary vascular
      resistance. We conclude that CHDF allows an adequate removal of fluid and waste
      products without deleterious effects on hemodynamics even in patients after
      cardiac surgery. CHDF is a safe and effective alternative in patients with CRF
      after cardiac surgery.

PMID- 9155124
TI  - [Surgical treatment of type A acute aortic dissection--experience of hypothermic
      circulatory arrest associated with the cerebroplegia].
AB  - From 1992 to July 1996, 19 patients (aged 39 to 78 years) were operated on for
      type A acute aortic dissection. Our operative strategy is that all patients in
      whom aortic dissection involves the segment of transverse aortic arch should
      undergo simultaneous replacement or repair of the aortic arch and ascending
      aorta. Among these 19 patients, 17 were operated on within 24 hours after onset.
      In 13 patients, graft replacement extended from the ascending aorta to the
      transverse portion of the arch. The aortic stumps were prepared with the Teflon
      left both inside and outside of the aortic wall. Recently these were
      reconstructed with the aid of the Gelatin-Resorcin-Formaling glue, instilled into
      the false lumen. Cerebral protection was achieved by hypothermic circulatory
      arrest associated with the cerebroplegia (thiopental, nicradipine and mannitol).
      In one patient associated with severe aortic regurgitation, a valved conduit was
      implanted and the coronary arteries were reimplanted. CABG was performed
      concomitantly in two patients for involvement of the proximal coronary arteries
      by the dissection process. The hospital mortality rate was 26% (5/19). However,
      in two of them, death was not directly related to the operative procedure. One
      patient died of graft versus host disease (GVHD), another patient died of acute
      epidural hemorrhage which was undetected until the repair was completed. During
      the postoperative course, in all but two patients, the false lumens of the aortic
      arch and/or descending thoracic aorta were confirmed to be totally thrombosed by
      the examination of CT scan and/or aortography. It is concluded that the surgical
      treatment of type A acute aortic dissection can be successfully performed, even
      if the graft replacement extended to the transverse aortic arch.

PMID- 9155125
TI  - [Two cases of tracheal injuries secondary to blunt trauma].
AB  - We present two cases of injury to the cervical trachea and the tracheal
      bifurcation due to blunt trauma. A 20-year-old man sustained complete disruption
      of the cervical trachea during a traffic accident. He underwent end-to-end
      anastomosis of the disrupted trachea. Nevertheless, 3 weeks after the initial
      surgery, tracheostomy was required because of suture failure. Two months after
      the second procedure, he underwent closure of the tracheostoma. Granulation
      developed temporarily, but diminished thereafter. The second case was a 14-year
      old boy. He sustained a longitudinal laceration about 3 cm from the tracheal over
      the membranous portion during a traffic accident. The laceration was successfully
      repaired by interrupted sutures with absorbable materials. Our experiences
      emphasize the importance of debridement of the injured cartilageous portion
      during treatment of tracheal injury due to blunt trauma and the difficulty in
      managing complete disruption of the cervical trachea with bilateral paralysis of
      the recurrent nerve.

PMID- 9155126
TI  - [Debakey IIIb aortic dissection from a distal arch atherosclerotic aneurysm--a
      case report].
AB  - We treated a 75-year-old male patient with DeBakey IIIb aortic dissection from a
      distal arch atherosclerotic aneurysm 75 mm in diameter. Arch replacement was
      carried out by separate extracorporeal circulation. The entry located juxta
      atherosclerotic aneurysm. It was considered that shear stress at the turning
      point of blood flow would occur the dissection. The relationship between the
      atherosclerotic aneurysm and the aortic dissection was studied.

PMID- 9155127
TI  - [Pulmonary arterial reconstruction with autologous pulmonary arterial tissue for
      pulmonary artery sling].
AB  - One-year and two-month-old boy with pulmonary artery sling underwent pulmonary
      artery reconstruction with autologous pulmonary arterial tissue. Surgical repair
      consisted of the transection of the left pulmonary artery at its origin with
      trimming a button hole and the creation of an oval hole with the same size to the
      left pulmonary button. An autologous pulmonary patch and the left pulmonary
      button were exchanged and sutured to the former partner's place. He recovered
      uneventfully in post-operative course. Postoperative CT revealed a well developed
      left pulmonary artery from 5 mm to 10 mm in diameter without any distortion or
      stenosis. This exchange method could allow the natural growth of the anastomotic
      places without narrowing or distortion.

PMID- 9155129
TI  - [A case of ventricular septal perforation treated surgically with an infarction
      exclusion technique].
AB  - We report an 85-year-old woman with postinfarction interventricular septal
      perforation. She underwent successful emergent surgical treatment by a slightly
      modified method based on David-Komeda's procedure. Perforation in this case
      occurred four days after acute myocardial infarction. Preoperative Qp/Qs was
      2.58, and pulmonary artery pressure was 34/25 mmHg. The area of infarction was
      large, and the perforation was the linear type 2.5 cm long near the apex. A probe
      was not able to pass through the perforation due to its complicated
      configuration. A double Xenomedica patch was sutured on the left side of the
      interventricular septum without excising the infarcted area. The suture line was
      placed on healthy myocardium apart from the infarcted area. The Xenomedica patch
      was sandwiched between the closure line of the ventriculotomy. Four days after
      surgery, residual shunt was observed by echocardiogram, but this subsequently
      disappeared on the 17th postoperative day. The patient was discharged from our
      hospital on the 57th postoperative day, and is now doing quite well.

PMID- 9155128
TI  - [A case report of primary repair for thoracic and thoracoabdominal and iliac
      artery aneurysms associated with severe visceral artery occlusive diseases--a
      redo operation for thoracoabdominal aortic aneurysm after infrarenal abdominal
      aortic aneurysm repair].
AB  - Abdominal aortic aneurysms can now be successfully repaired with low mortality
      and few early complications. On the other hand, the cases that required
      operations for recurrent aneurysms have been increased during long term follow-up
      period. In such cases, there are many difficulties for operative procedures
      compared to their first operations and many risk factors. A case of successful
      operation for the thoracoabdominal aortic aneurysm associated with severe
      stenotic lesions of the visceral arteries and descending thoracic aneurysm and
      left common iliac artery aneurysm are reported. A 74-year-old man who underwent
      operation for infrarenal abdominal aortic aneurysm and left nephrectomy 7 years
      and 9 months ago at our institution developed an aneurysm just above the proximal
      anastomosis with severe stenotic lesions of the visceral arteries. At the same
      time, descending thoracic aortic aneurysm and left common iliac artery aneurysm
      were associated. And he had ischemic heart disease. Under selective perfusion of
      the visceral arteries, graft replacement of these aneurysms and reconstruction of
      superior mesenteric artery and right renal artery were done. The patient had good
      post operative course and started oral feeding at 3 post operation day. He
      returned to his occupation and is doing well with no trouble one and half year
      after operation.

PMID- 9155130
TI  - [A case of Ellis-van Creveld syndrome with partial atrioventricular septal defect
      and double orifice mitral valve].
AB  - Ellis-van Creveld Syndrome (ECS) is characterized by chondrodysplasia, ectodermal
      dysplasia, polydactyly, and congenital cardiac defects. As congenital cardiac
      defects, single atrium and endocardial cusion defect are frequent in literatures.
      We described a case, a 68-year-old woman, presenting with ECS with partial
      atrioventricular septal defect and double orifice mitral valve. The partial
      atrioventricular septal defect was repaired by closure with a Dacron patch. The
      accessory orifice was located at the anterior cusp of the mitral valve, which was
      left, untouched, because no regurgitation had been detected preoperatively. Her
      postoperative course was uneventful, and the patient was discharged on 25th
      postoperative day.

PMID- 9155131
TI  - [Successful aortic root replacement with pulmonary autograft (Ross) in two cases
      of congenital aortic stenosis].
AB  - Two cases of 7 and 23 year of age with congenital aortic stenosis associated with
      the small valve annulus underwent successful aortic root replacement with
      pulmonary autograft (Ross procedure). Preoperative pressure gradient and the
      valve size were 120 and 80 mmHg, and 16 and 18 mm, respectively. Even with the
      small native aortic annulus, pulmonary autografts could be implanted to aortic
      annulus without autograft distortion by the method of total aortic replacement.
      The right ventricular outflow reconstruction was performed with PTFE-valved
      bovine pericardial conduit with securing the posterior muscular edge by a strip
      of autologous aortic wall. Postoperative course in both patients was uneventful
      without any rhythm disturbances. During the 12 and 14 months of follow-up, both
      patients were in excellent clinical condition with no evidence of autograft valve
      regurgitation and functional deterioration of valved conduit. This procedure was
      thought to be a preferable method of young cases with congenital aortic stenosis.

PMID- 9155132
TI  - [Extended aortoplasty for supravalvular aortic stenosis with Williams syndrome].
AB  - We report a male case of supravalvular aortic stenosis associated with Williams
      syndrome requiring surgery at age 11. At 5 years of age, this boy presented with
      a harsh systolic heart murmur and was diagnosed as having a supravalvular aortic
      stenosis. In association with mental retardation, elfin face and bilateral
      inguinal hernias, he was diagnosed as a Williams syndrome confirmed by the
      chromosomal analysis revealing the deletion of 7q11.23. The pressure gradient
      across the stenotic lesion of the ascending aorta, which had been 35 mmHg at age
      5, progressed to 80 mmHg at age 11 years. Extended aortoplasty was performed
      using a patch of 20 mm Hemashield graft prosthesis. Postoperative cardiac
      catheterization confirmed that the pressure gradient in the ascending aorta
      completely disappeared following surgery.

PMID- 9155133
TI  - [Surgical treatment for primary cardiac malignant lymphoma].
AB  - A 60-year-old woman who complained of palpitation was diagnosed as ventricular
      tachycardia on electrocardiography and admitted to our hospital. The ultrasonic
      cardiography showed cardiac tumor in right ventricle and right atrium. Due to the
      obstruction of the right ventricle inflow by the tumor, we immediately performed
      resection of cardiac tumor and repair of right ventricle wall under
      cardiopulmonary bypass. The tumor was diagnosed as malignant lymphoma by
      pathological examination for surgical specimen of tumor. After operation her
      general condition was good, but residual cardiac lymphoma developed large size.
      We performed radiation therapy for cardiac lymphoma. Therefore the lymphoma was
      reduced to minimum size. Six months after operation metastatic malignant lymphoma
      appeared at whole body. So we performed chemotherapy for reduction of systemic
      malignant lymphoma. At first the chemotherapy was very effective. But metastasis
      spread rapidly and effectiveness of chemotherapy reduced. Thirteen months after
      operation she died for respiratory distress, probably due to metastatic brain
      tumor.

PMID- 9155134
TI  - [Two cases of annulo-aortic ectasia with type A aortic dissection reconstructed
      by reimplantation of the aortic valve].
AB  - We performed aortic valve sparing operation in two cases of annulo-aortic ectasia
      combined with Type A aortic dissection. Marfan syndrome was found in one case and
      the dissection was acutely evolving in another case. The aortic valves were
      observed as normal configuration in both cases and then reimplanted within the
      synthetic grafts along with the David's procedure. No aortic regurgitation was
      found in the acute case but slight regurgitation was checked out in the Marfan
      case at the discharge. The aortic valve preserving operation for annulo-aortic
      ectasia was considered much effective in cases with aortic dissection in order to
      expect the thrombolization in the pseudo lumen.

PMID- 9155135
TI  - [Primary surgical repair of aorticopulmonary septal defect with coarctation of
      the aorta].
AB  - Two infants with aorticopulmonary septal defect (APSD) and coarctation of the
      aorta (CoA) underwent primary surgical repair and their aortic arches were
      reconstructed in a manner of end-to-end anastomosis. One of the cases, 4-day-old
      girl and Type I of Mori's classification, underwent Sandwich patch closure of the
      communicating vessel. The other, 40-day-old girl and Type III, underwent division
      of he communicating vessel. Aortic wall was primarily closed and pulmonary artery
      was reconstructed with a pericardial patch. Both survived the surgery, and are
      well without medication at 13 and 14 postoperative months. Interrupted aortic
      arch is commonly known as the associated aortic arch anomaly of APSD, and to the
      best of our knowledge, this is the first report of CoA as the associated anomaly
      of APSD. Whichever the anomaly of the aortic arch, early diagnosis and primary
      surgical repair in the early ages are urgently needed for favorable outcome of
      the patient.

PMID- 9155136
TI  - [Report on a case of adult rhabdomyosarcoma subjected to tumorectomy and
      lobectomy].
AB  - Rhabdomyosarcoma (RMS) rarely occurs in adult and intra thoracic activity. This
      is a report on a case we experienced of adult RMS, which was subjected to
      tumorectomy and lobectomy. The patient was a 23 years old male, who first
      consulted a hospital in his neighborhood due to anterior chest pain suffered
      since May 1995. Since the examination showed an abnormal shadow in right anterior
      mediastinum, the patient was referred to our department. By biopsy under CT, the
      patient was diagnosed as having embryonal type of RMS and underwent surgery. The
      outcome was good and the patient is currently in the course of chemotherapy using
      IRS (Inter-group Rhabdomyosarcoma study)-III.

PMID- 9155137
TI  - [A case report of cervicomediastinal lipoma].
AB  - We experienced a case of cervicomediastinal lipoma. The patient was a 3-year-old
      boy suffering from low-grade fever and dry cough. We detected an abnormal shadow
      on a chest X-ray film. Subsequent CT and MRI demonstrated a nonhomogeneous mass
      extending from the posterior mediastinum to the right side of the neck. We
      performed an operation for the mediastinal tumor under median sternotomy and
      right neck incision. The encapsulated tumor was 11 x 6 x 8 cm in size and was
      histologically diagnosed as myxolipoma. The nonhomogeneity of the tumor was due
      to myxomatous degeneration of the adipose tissue. Although this case was
      complicated by Horner's syndrome, the postoperative course was relatively fair.

PMID- 9155138
TI  - [Video-assisted thoracoscopic surgery for a 89-year-old patient with primary lung
      cancer--report of a case].
AB  - A 89-year-old woman was referred to our hospital because of a relatively defined
      shadow of the right peripheral lung in chest roentgenograms. Although this case
      couldn't be diagnosed with transbronchial lung biopsy, adenocarcinoma of the lung
      (c-T1N0M0) was suspected because of radiological findings. We planned video
      assisted pulmonary partial resection of the S6 in consideration of age and
      general status. Her postoperative courses was uneventful with no complications.
      Video-assisted thoracoscopic surgery is one of the treatments for elderly
      patients with peripheral early stage lung cancer.

PMID- 9155139
TI  - [Emergency surgery making use of video-assisted thoracoscopy--2 case reports].
AB  - We recently experienced two emergency operating cases using video-assisted
      thoracoscopy. First case was a 17-year-old male with foreign body and
      pneumothorax in the right thorax. He was emergencilly treated by means of video
      assisted thoracoscopic surgery. The operation was carried out using double-lumen
      endotracheal anesthesia. Short trocars were inserted through the right
      intercostal spaces to introduce a flexible video thoracoscope and surgical
      instruments. Foreign body was looked for easily and removed out. Second case was
      a 22-year-old male with hemo-pneumothorax at the right side. He was treated using
      video-assisted thoracoscopy emergencilly. Bleeding point was searched and
      hemostasis was done by the electrical mess and the clip. Bulla was removed out
      with surgical instruments. These were good adaptation of emergency operation
      using video-assisted thoracoscope. The advantages of this thoracoscopic surgery
      are: less operative invasion and postoperative pain, early recovery and short
      hospital stay, and cosmetic preservation.

PMID- 9155140
TI  - [David's operation for aortic regurgitation associated with annulo-aortic
      ectasia].
AB  - A 54-year-old man with AR due to AAE underwent the replacement of ascending aorta
      by sparing an aortic valve (David operation). Under cardiopulmonary bypass, the
      aneurysmal aorta and the all three sinuses of valsalva were excised, leaving 5 mm
      of arterial wall attached to the aortic valve. The aortic valve was reimplanted
      inside a Dacron graft (28 mm Hemashield) which was calculated by aortic valve
      leaflet height as well as from the size of LVOT. The patient has survived the
      operative procedure and showed uneventful recovery. We believe this new procedure
      preserving the native aortic valve is useful for preventing from some
      complications associated with an artificial heart valve and improvement of QOL of
      patient.

PMID- 9155141
TI  - [A case of scheduled mitral valve replacement for mitral regurgitation caused by
      papillary muscle rupture after acute myocardial infarction].
AB  - Mitral regurgitation caused by papillary muscle rupture after acute myocardial
      infarction has poor prognosis, and it is the usual course for such cases in
      cardiogenic shock to be performed early mitral valve replacement. However, we
      recently experienced a case of successful scheduled mitral valve replacement for
      mitral regurgitation caused by rupture of the posterior papillary muscle after
      acute inferior myocardial infarction. The patient was a 63-year-old woman who
      admitted to a hospital with back pain and dyspnea and was diagnosed as pulmonary
      edema due to mitral regurgitation after acute myocardial infarction. She was
      treated with dopamine and diuretic agents effectively, but not weaned from these
      drugs. Then, she was transferred to our hospital. At the admission, she was in
      the NYHA class II due to mitral regurgitation and inferior myocardial infarction
      with papillary muscle rupture revealed by transesophageal echocardiography.
      Cardiac catheterization demonstrated total occlusion of the proximal right
      coronary artery (segment #2) and mitral regurgitation in Sellers III. The patient
      underwent a successful scheduled mitral valve replacement with SJM 27M
      concomitant with coronary artery bypass grafting 47 days after the onset of acute
      mitral regurgitation. There are few reports that successful surgical treatment
      for papillary muscle rupture was done more than 4 weeks after the onset of mitral
      regurgitation in Japan.

PMID- 9155142
TI  - [A case of right ventricular myxoma].
AB  - A 43-year-old male presented with a history of occasional syncopal episodes and
      general fatigue for 4 months. On admission, a grade 4/6 systolic murmur was
      noted, and the electrocardiogram demonstrated frequent premature supraventricular
      beats. An echocardiogram revealed the presence of a multi-lobular mass in the
      right ventricle which prolapsed into the pulmonary artery during systole.
      Ultrafast computed tomography demonstrated a pedunculated mass arising from the
      right ventricular free well. At operation, the soft mass was excised through the
      tricuspid valve under cardiac arrest. Histopathologically, the tumor was
      diagnosed as a myxoma. Myxoma of the right ventricle occurs very rare. We review
      the literature relevant to cardiac myxoma.

PMID- 9155143
TI  - [A successful surgical case report of impending rupture of the true thoraco
      abdominal aortic aneurysm induced by thrombosed-type acute aortic dissection
      (Stanford type A)].
AB  - Impending rupture of the true aneurysm of the thoraco-abdominal aorta induced by
      acute aortic dissection (Stanford type A) is very rare, and decision making of
      the therapeutic plain is difficult. A 88-year-old woman manifested severe back
      pain with hypotension. Chest computed tomographic examination revealed a true
      aneurysm of the thoraco-abdominal aorta and acute thrombosed-type aortic
      dissection (Stanford type A) with cardiac tamponade. Under the diagnosis of
      impending rupture of the thoraco-abdominal aortic aneurysm induced by acute
      aortic dissection (Stanford type A), graft replacement of the thoraco-abdominal
      aortic aneurysm and pericardial drainage were successfully performed. Two months
      later, computed tomographic examination revealed disappearance of the thrombosed
      false lumen in the ascending aorta.

PMID- 9155144
TI  - [Ruptured descending thoracic aortic aneurysm due to aortitis syndrome--a case
      report].
AB  - Ruptured fusiform descending thoracic aortic aneurysms due to aortitis syndrome
      are rare. A 29-year-old woman was readmitted to our hospital with a chief
      complaint of back pain and shock, and diagnosed as having rupture of a descending
      thoracic aortic aneurysm. She had a past history of aortitis syndrome beginning
      eight years ago. On chest CT examination earlier a year, the descending thoracic
      aortic aneurysm was 4.5 cm in diameter, and calcification we observed in the
      aortic wall. An inflammatory reaction had been controlled by steroid therapy and
      her blood pressure had been controlled by vasodilator drugs. Emergent graft
      replacement of a descending aortic aneurysm was successfully performed under a
      femoro-femoral bypass using a centrifugal pump and membrane oxygenerator, and
      Cell Sver. Although in the literature surgical treatment is indicated only if
      there is a symptomatic or enlarging aneurysm especially of saccular type and no
      operation is justified for an aortic aneurysm showing marked calcification, we
      concluded that aggressive surgical treatment was necessary for this fusiform
      aneurysm due to aortitis syndrome.

PMID- 9155146
TI  - [Anticancer drugs and pharmacologic actions].
AB  - Anticancer drugs are traditionally classified either by their mechanism of action
      or by their origins. Alkylating agents are reactive to DNA and cellular proteins
      and the primary mode of action is mostly through cross-linking of DNA strands,
      inhibiting replication of DNA and transcription of RNA. Some antimetabolites are
      structural analogs of normal molecular essentials for cell growth. After intaking
      into cells the analogues change to substances to interfere with DNA or RNA
      synthesis. Drugs derived from microorganism are called antitumor antibiotics.
      Some plants alkaloids blind to tublin and inhibit the formation of microtubules
      causing metaphase arrest, while camptothecins inhibit topoisomelase 1. Other
      compounds which are not classified to any categories expects characteristic mode
      for action to induce cell death or differentiation.

PMID- 9155147
TI  - [Multidrug resistance of cancer cells mediated by ABC superfamily transporters].
AB  - ATP-binding cassette(ABC) superfamily transporters, including P-glycoprotein and
      MRP, actively transport various structurally dissimilar chemotherapeutic
      compounds out of cancer cells and confer multidrug resistance. Members of ABC
      superfamily which may extrude anti-cancer drugs are still expanding, thus the
      importance of these proteins are further increasing for cancer chemotherapy.
      Multidrug resistance will be acquired either by the induction of expression of
      ABC superfamily transporters or by mutations of ABC superfamily genes which cause
      amino acids substitutions. We recently found that amino acid substitutions in the
      first predicted transmembrane domain of P-glycoprotein increase the ability to
      confer resistance to important anti-cancer drugs adriamycin and VP-16. The
      mechanisms for drug recognition and transport of human P-glycoprotein and MRP are
      discussed.

PMID- 9155148
TI  - [Acquisition of resistance to anticancer agents by overproduction of target
      enzymes].
AB  - Antimetabolic anticancer agents possess their own target enzymes: that of
      methotrexate is dihydrofolate reductase; 5-fluorouracil and ZD1604, thymidylate
      synthase; hydroxyurea, ribonucleotide reductase; 2'-deoxycoformycin, adenosine
      deaminase; N-(phosphonacetyl)-L-aspartate, aspartate transcarbamylase.
      Overproduction of each target enzyme has been observed with various animal and
      human cell lines which acquired resistance to all these agents. These facts
      suggest that this is a common mechanism for resistance to these agents. Most of
      these resistant cells showed amplification of the corresponding genes in double
      minute chromosome or homogeneously stained region of the chromosome. The relation
      between the degree of resistance and those of enzyme overproduction, the
      expression and amplification of the gene coding for each enzyme protein in
      various resistant cell lines are demonstrated and discussed.

PMID- 9155149
TI  - [Acquisition of resistance associated with impairment of metabolic activation of
      anticancer drugs].
AB  - Some of anticancer drugs must undergo bioactivation in order to exert their
      anticancer activity. Those include most of antimetabolites, mitomycin C,
      cyclophosphamide and a camptothecin analog CPT-11. The latter two drugs are
      usually activated in liver or plasma, and the others are converted to active
      metabolites in the target cells. A number of biochemical mechanisms of resistance
      have been proposed and for the drugs to be activated in cancer cells impairment
      of activation enzymes were reported as one of the mechanisms; for example,
      deoxycytidine kinase for cytarabine and gemcitabine, orotate phosphoribosyl
      transferase for 5-fluorouracil, hypoxanthine-guanine phosphoribosyl transferase
      for 6-mercaptopurine, folylpolyglutamate synthetase for methotrexate and DT
      diaphorase for mitomycin C were concerned.

PMID- 9155150
TI  - [Multidrug-resistance by induction of inactivation for anti-cancer drugs].
AB  - There are several major groups of multidrug resistance mechanisms. 1) The
      multidrug resistant phenotype. 2) Glutathione S-transferences (GST) and
      detoxification mechanisms. 3) Topoisomerase I and II. 4) DNA repair. 5) Drug
      activation by cytochrome P450 (P450). In this article the biochemical functions
      of GST and P450 are described to show how individual enzymes contribute to
      resistance to carcinogens and anti-tumor drugs. Cancer cell lines indicated
      resistant to anti-cancer drugs, such as mitomycin C, doxorubicin, tamoxifen,
      cyclophosphamide and their derivatives, by a high activity of GST and a low
      activity of P450 in general. However, the mechanism of change of these enzyme
      activities is complicated and different in each drug. We show the study on the
      mechanism of multidrug resistance using cancer cell lines.

PMID- 9155151
TI  - [Clinical criteria of chemosensitivity test].
AB  - Chemosensitivity test is useful in evaluating the appropriate cancer chemotherapy
      for solid tumors which are less sensitive to conventionally available antitumor
      agents. Most of assays used in clinics are in vitro assay, in which the cutoff
      concentration and contact time should be determined to mimic the clinical
      response of the chemosensitivity test. Since the antitumor effect of most of
      antitumor agents depends on their concentration x contact time, and the contact
      time will be determined according to the assay, the cutoff concentration will be
      calculated from the cumulative efficacy curve or 50% inhibitory concentration and
      in vivo response of human tumor xenografts in nude mouse. The clinical result
      obtained from chemosensitivity test was discussed.

PMID- 9155152
TI  - [Molecular mechanism of the stress induction of MDR1 gene].
AB  - MDR1 promoter activity increases in response to various environmental stimuli,
      including anticancer drugs and in a manner that is dependent on the inverted
      CCAAT box. The binding activity of a nuclear factor MDR-NF1 that interacts with
      this promoter region was augmented when the nuclear extract was prepared from
      cells that had been treated with either UV or anticancer drugs. In an attempt to
      understand the molecular basis for the stress-dependent induction of MDR1
      promoter activity, the cDNA for MDR-NF1 have been cloned. The amino acid sequence
      encoded by the cloned cDNA was identical to that of YB-1. The human Y-Box binding
      protein (YB-1) is a member of a DNA-binding protein family with a structurally
      and functionally conserved cold shock domain. YB-1 was found to be much higher in
      all cisplatin-resistant cell lines than that in the respective drug-sensitive
      parental counterparts. Two transfectants with a YB-1 antisense construct showed
      increased sensitivity to cisplatin, mitomycin C and UV irradiation, but not to
      vincristine, doxorubicin, camptothecin or etoposide. Thus, YB-1 may protect cells
      from the cytotoxic effects of agents that induce cross-linking of DNA, suggesting
      a novel function of this ancestor DNA binding protein. Regulatory mechanism of
      the YB-1 gene expression and the cellular functions of YB-1 are currently under
      investigation in relation to drug resistance.

PMID- 9155153
TI  - [Tissue distribution of the multidrug-resistance gene product P-glycoprotein and
      its physiological function].
AB  - In normal tissues, P-glycoprotein(P-gp), which is expressed in various tumor
      cells, is found on the luminal surface of epithelia of the kidney proximal
      tubule, small intestine and colon and bile canalicular face of hepatocytes, as
      well as, in the adrenal and capillary endothelial cells in the brain and testis.
      The physiological function of P-gp remains unclear but growing amounts of
      information suggest that it can play a important role in the absorption from
      intestine, elimination from liver and kidney and distribution into brain across
      the blood-brain barrier for many cancer chemotherapeutic agents as well as other
      drugs which reverse multidrug resistance. The competition for the P-gp-mediated
      transports in tissues and organs, which express multidrug-transporter, might lead
      to unsuspected drug interactions among these drugs.

PMID- 9155154
TI  - [Detection of P-glycoprotein and its clinical significance].
AB  - There is considerable variation in the assays used to evaluate the expression of
      mdr1 in various human malignancies. Current methodology includes reverse
      transcriptase polymerase chain reaction (RT-PCR) for assay of mdr1 mRNA, and
      immunohistochemistry or flow cytometry for detection of the multidrug
      transporter, P-glycoprotein(P-gp). Normal tissues, such as gastrointestinal
      mucosa, biliary tract and kidney, express high levels of P-gp, which suggests
      physiologic functions for this transporter. The some evidence suggests that mdr1
      expression is a prognostic factor for response to chemotherapy, as well as for
      subsequent survival in various kind of tumors. We have developed a novel method
      using flow cytometry for detection of P-gp in gastric carcinomas. A strong
      correlation was noted between the flow cytometric data and the degree of drug
      resistance assessed by thymidine incorporation assay (TIA). We believe that this
      technique may have a significant potential to be utilized in prediction of P-gp
      related drug resistance in clinical cancer chemotherapy.

PMID- 9155155
TI  - [The role of P-glycoprotein in the liver].
AB  - P-glycoprotein, the MDR1 gene product which confers multidrug resistance to tumor
      cells and transports cationic or neutral compounds with high lipophilicity
      outward from the cells, excretes xenobiotics into the lumen in the kidney, small
      intestine and liver. The expression of P-glycoprotein is enhanced by stresses
      including exposure to various xenobiotics, while the activity is regulated to
      some extent by the phosphorylation. P-glycoprotein and P450 3A have similar
      substrate specificities and inducers, which may suggest they have complementary
      roles in the liver. The other subclass, MDR3, which does not show the multidrug
      resistance, translocates phosphatidyl choline selectively into the outer leaflet
      of the liver canalicular membrane, and may protect the liver from the detergent
      effect of bile acids.

PMID- 9155156
TI  - [Multidrug resistance protein (MRP)].
AB  - Two different integral glycoproteins, the 170 kD P-glycoprotein(P-gp) and the 190
      kD multidrug resistance protein (MRP), are involved in the acquisition of
      multidrug resistance phenotypes in cancer cells. These two proteins belong to the
      ATP-binding cassette (ABC) superfamily but their primary structures are quite
      dissimilar, sharing only approximately 15% amino acid identity. Nevertheless, MRP
      and P-gp confer resistance to a similar profile of chemotherapeutic agents. These
      two proteins seem to play a similar role in the acquirement of multidrug
      resistance. However, it has recently been demonstrated that MRP can specifically
      transport the cysteinyl leukotriene, LTC4, and some other glutathione conjugates,
      suggesting that MRP had a function different from P-gp. This review summarizes
      the current data on the structural and functional characteristics of MRP, its
      ability to confer multidrug resistance and its clinical relevance in drug
      resistant malignant disease.

PMID- 9155157
TI  - [ATP-dependent glutathione conjugate export pump].
AB  - KCP4 cells are resistant to cisplatin and have a GS-X pump different from MRP.
      The GS-X pump was suggested to be involved in reducing the accumulation of
      cisplatin in KCP-4 cells. The expression of cMOAT was 4-to 6-fold higher in KCP-4
      cells and two other cisplatin-resistant human cell lines. It is still not clear
      whether the cisplatin resistance in KCP-4 cells are attributed to cMOAT. Other
      members of the MRP/GS-X pump family have been reported. Amino acid sequence of
      EBCR of rabbit is 91% identical to that of human cMOAT. On the view of cancer
      chemotherapy, it is very important to understand the structure and function of GS
      X pumps since they may be involved in not only drug resistance but also drug
      metabolism and side effects.

PMID- 9155158
TI  - [Metallothionein].
AB  - Metallothionein is a low-molecular weight protein involved in resistance to
      toxicity of heavy metals. Recent experimental evidences indicate that
      metallothionein appears to be a factor in determining the responsiveness of tumor
      cells to anticancer drugs, such as cisplatin and adriamycin. The resistance of
      tumor cells having high concentration of metallothionein to cisplatin has been
      observed in cultured cells and transplanted tumors. On the other hand, increase
      in metallothionein concentration in normal tissues of tumor-bearing animals
      prevents side effects of anticancer drugs. Metallothionein may be an important
      endogenous factor in cancer chemotherapy.

PMID- 9155159
TI  - [DNA topoisomerases targeting anticancer agents and mechanism for acquirement of
      drug resistance].
AB  - DNA topoisomerase(topo) I and II regulate the topological conformation and DNA
      molecules by catalyzing the concerted breakage of single or double strands. Topo
      I and II targeting anticancer agents such as camptothecins (CPT-II),
      epipodophyllotoxins (VP16 and VM26), and amsarcine are widely used in cancer
      chemotherapy. To enhance their therapeutic efficacies, one should understand how
      cellular sensitivities to these topo-targeting agents are regulated, and one
      should also understand what mechanisms or factors are involved in the appearance
      of tumor cells resistant to them. We will discuss if there is any marker useful
      for determining drug sensitivity to these topo-targeting agents in cancer cells.

PMID- 9155160
TI  - [Cyclosporine as drug resistance modifiers; mechanism and clinical
      investigation].
AB  - Multidrug resistance(MDR), mediated by P-glycoprotein, is a well-understood
      mechanism of resistance to anticancer drugs. P-glycoprotein is thought to act as
      an efflux pump with broad specificity for variety of anticancer drugs.
      Cyclosporine and its analogue, SDZ PSC 833, have demonstrated ability to inhibit
      P-glycoprotein mediated transport function, restore accumulation defects for
      anticancer drugs, and reverse resistance in vitro and in vivo. The clinical
      trials of these drugs are on going. P-glycoprotein may also play a pivotal role
      in the evolution of pharmacological defence mechanisms, protecting organisms from
      cytotoxic agents. Approach to overcome resistance may result in serious
      challenges to the host's natural defenses. Clinical trials of MDR modulators,
      such as cyclosporine or SDZ PSC 833, should be designed with caution and with
      careful consideration for potential pharmacokinetic and pharmacodynamic
      interaction.

PMID- 9155161
TI  - [Overcoming of multidrug resistance and its clinical application].
AB  - P-glycoprotein plays a key role in the mechanisms of multidrug resistance in
      experimental tumors as well as in clinical tumors in acquired-type resistance and
      in intrinsic-type resistance. Thus the therapeutic approaches targeting the P
      glycoprotein would provide benefits in eradication of drug-resistant tumor cells.
      Practical approaches to overcoming of multidrug resistance by targeting the P
      glycoprotein would be; to use agents including calcium channel blocker-related
      agents and membrane-modifying agents that interact with P-glycoprotein, although
      some potential problems concerning side effects still remained to be studied.

PMID- 9155162
TI  - [Circumventing multidrug resistance in human cancer by anti-ribozyme].
AB  - The demonstration tha RNA can be cleavaged by cis-ribozyme(catalytic RNAs, RNA
      enzyme) has potentially important therapeutic implications. Ribozymes are
      effective for modulation of gene expression because of their simple structure,
      site-specific cleavage activity and catalytic potential. The targets of ribozyme
      mediated gene modulation have ranged from cancer cells to foreign genes that
      cause infectious diseases. Additional target sites for ribozymes are in initial
      phases of development and design. Ribozymes have been targeted against myriad
      genes, including oncogenes (ras, BCR-ABL) and drug resistance genes(MDR-1, c-fos,
      DHFR). These ribozymes have cleaved the target RNAs in culture system(in vitro)
      and developed in vivo system. We reported that anti-fos ribozyme has altered the
      expression of c-fos and DNA repair genes in cisplatin-resistance cancer cells,
      and reversed the sensitivity to ciaplatin. Furthermore, we have developed high
      efficiency by the transfer system using an electroporation in vivo.

PMID- 9155163
TI  - [Overcoming of multidrug resistance by a newly synthesized quinoline compound, MS
      209].
AB  - The emergence of multidrug resistance(MDR) is a major problem in cancer
      chemotherapy. Many compounds are developed to reverse MDR, and some of them are
      under clinical trials. Among them, MS-209, a novel quinoline derivative, is one
      of the most potent MDR reversing agents. MS-209 at 3 microM effectively reverses
      MDR in various cell lines in vitro. MS-209 directly interacts with P-glycoprotein
      and inhibits the P-glycoprotein-mediated drug transport. Oral administration of
      MS-209 combined with anticancer drugs markedly increases the life span of mice
      bearing MDR tumor cells without causing serious side effects. Thus, MS-209 is an
      orally active and potent MDR reversing drug without serious side effects.

PMID- 9155164
TI  - [Overcoming of multidrug resistance by anti-P-glycoprotein monoclonal antibody].
AB  - P-glycoprotein is one of the key molecules in multidrug resistance. Monoclonal
      antibodies against P-glycoprotein could be useful tools for killing MDR tumor
      cells. To overcome multidrug resistance, many anti-P-glycoprotein monoclonal
      antibodies have been made such as MRK16 and MRK17. Conjugated moAb, such as
      bispecific antibody, immunotoxin and radioisotope conjugates have also been
      constructed to enhance the anti-tumor activity of moAb. Cytokine-gene
      transduction for accumulation and activation of monocytes may be hopeful to
      augment the therapeutic efficiency of anti-P-glycoprotein antibody. For clinical
      use, construction of human moAb, overcoming tumor heterogeneity, and protection
      of normal tissue by specifically targeting the tumor cells should be essential.

PMID- 9155165
TI  - [Search for new MDR modifier possessing taxane skeleton].
AB  - Among new taxoids, taxuspines A-H and J-T, and known taxoids containing taxol and
      taxol-type compounds with an N-acylphenylisoserine group at C-13 and an oxetane
      ring at C-4 and C-5 isolated from stems and leaves of the Japanese yew Taxus
      cuspidata Sieb. et Zucc., two non-taxol-type compounds remarkably reduced CaCl2
      induced depolymerization of microtubules. Furthermore, seven non-taxol-type
      compounds increased cellular accumulation of vincristine in multidrug
      resistant(MDR) tumor cells as potent as verapamil, while taxol and taxol-type
      compounds did not show such an activity. In addition, the non-taxol-type
      compounds enhancing vincristine accumulation inhibited competitively binding of
      azidopine to P-glycoprotein. These results suggest that some non-taxol-type
      taxoids may be useful for overcoming MDR in tumor cells.

PMID- 9155166
TI  - [Mechanism on androgen-independent progression of prostate cancer].
AB  - Eighty percent of prostate cancer with metastasis respond to androgen ablasion,
      showing initial androgen-sensitive growth. However, more than half of responders
      gradually loses dependency up to 5 years. Animal experiments reveal that loss of
      androgen sensitivity is attributable to complex reasons; adaptation, paracrine
      control by other androgen-independent tissues, genetic changes and mutation of
      androgen receptor. Most important event is explained from alteration of
      expression on oncogenes and suppressor genes. Counterplan of the progression was
      discussed.

PMID- 9155167
TI  - [Mechanism of acquired antiestrogen resistance and its management in breast
      cancer].
AB  - Although non-steroidal antiestrogen, tamoxifen(TAM), has been known to be useful
      for estrogen receptor(ER)-positive breast cancer, acquired tamoxifen resistance
      frequently occurs during the treatment. Several factors seem to be responsible
      for the resistance; decreased level of ER, mutation of ER, agonistic effect of
      TAM, ovarian steroidogenesis, altered metabolism of TAM, and increased expression
      level of antiestrogen binding sites. Withdrawal of TAM and second-line endocrine
      therapy might be effective on the tamoxifen resistant breast cancer which retains
      estrogen dependency. Otherwise, chemotherapy should be chosen for estrogen
      independent breast cancer which has lost ER and fails to respond to other
      endocrine therapy. In this context, the menstrual status, serum level of
      estradiol, and steroid receptor status should be considered for the management of
      acquired antiestrogen resistance in breast cancer.

PMID- 9155168
TI  - [Kinds of antimicrobial agents and their mode of actions].
AB  - Hardness of development of drug-resistant bacteria has cross relation with
      mechanisms of antibacterial activities of antimicrobial agents. When the site of
      action of certain antibiotic is single enzyme and the enzyme can be converted to
      tolerant against the antibiotic by change of single amino acid retaining the
      enzymatic activity, drug-resistant bacteria can emerge easily. On the other hand,
      if the site of action is complex metabolic reactions, the drug-resistant bacteria
      would emerge hardly, because multiple mutations are required in this case. So
      that knowledges of mechanisms of antimicrobial agents are important to prevent
      the development of drug-resistant bacteria. Antimicrobial agents are classified
      into several categories, i.e. inhibitors for bacterial cell wall such as beta
      lactam drugs, fosfomycin, and vancomycin; inhibitors for protein biosynthesis
      such as tetracyclibnes, macrolides, aminoglycoside antibiotics; inhibitors for
      DNA synthesis such as 4-quinolones; inhibitors for RNA synthesis such as
      rifampicin.

PMID- 9155169
TI  - [The mutation and the selection of inactivating enzymes against antibiotic
      resistances].
AB  - The genes coding for inducible beta-lactamase production from S. aureus pI258
      showed constitutive expression in E. faecalis. These findings suggest that
      constitutive beta-lactamase production in E. faecalis is due to not only to the
      absence of functional regulatory genes but to some factors as well. However,
      hypothetical model for control of the expression of inducible ampC genes in Grm
      negative bacteria is slightly different to that of S. aureus and E. faecalis. The
      muropeptide GlcNac-anhMurNac-tripeptide, tetrapeptide and pentapeptide are
      transport into the cytoplasm through AmpG. Intracellular accumulation of GlcNac
      anhMurNac-tripeptide as the results of the presence of the beta-lactam
      antibiotics or of anhMurNac-tripeptide as the results of inactivation of ampD
      triggers production of E. cloacae AmpC beta-lactamase. The muropeptides
      presumably bind to the ampR, the transcriptional regulator, and convert it into
      an activator for ampC expression.

PMID- 9155170
TI  - [Acquisition of antibiotic-resistance in bacteria by alteration of molecular
      target, or by the decreased permeability].
AB  - The target of an antibiotic is any essential enzyme for bacterial growth and
      quantitative or qualitative alteration of the enzyme or its substrate may cause
      resistance to the drug. Thus, the alteration of DNA gyrase and/or topoisomerase
      IV may result in resistance to fluoloquinolones, and alteration of beta-subunit
      of RNA polymerase may cause rifampicin-resistance. The cell wall synthesizing
      enzymes which cross-bridge peptidoglycan units are called PBPs and their
      alteration cause resistance to beta-lactams, and the alteration of the substrate
      D ala-D ala to D ala-D lactate causes vancomycin-resistance. In other drug
      resistances, various instances of alteration of enzymes are known. Drug
      resistances are also brought about by decreased permeability of the drug. Some
      instances are described.

PMID- 9155171
TI  - [Antibiotic extrusion and multidrug resistance].
AB  - Many bacteria evolved to have machineries that extrude noxious compounds across
      the cell membranes. Extrusion of such compounds through membranes of gram
      negative bacteria is a complex, since the compounds need to cross two membranes.
      Typically, Pseudomonas aeruginosa and Escherichia coli produce power-operated
      antibiotic extrusion pumps and the exit membrane channel located in the inner and
      the outer membranes, respectively. The membrane fusion protein anchoring in the
      inner membrane and largely protruding the periplasmic space connects these two
      membrane proteins to facilitate extrusion of antibiotics.

PMID- 9155172
TI  - [Mechanism of acquiring drug-resistance genes in pathogenic bacteria].
AB  - Pathogenic bacteria acquire resistance to chemotherapeutic agents by mutational
      events in the intrinsic genes or by incorporating foreign resistance genes. The
      resistance genes to various drugs were transferred among bacteria by
      transformation with free DNA, phage-mediated transduction, or cell to cell
      conjugation. Plasmids are capable of self-replication and self-transfer by
      conjugation. Drug-resistance genes are incorporated into plasmids by transposable
      elements, transposons. Several kinds of transposons carrying resistance genes to
      various drugs, or some transposons carrying multiresistance genes, are mobile
      among genetic elements and confer multiresistance on pathogenic bacteria. There
      is a specific element, integron, on transposons or plasmids. The integron has the
      gene and the site for incorporating resistance genes as cassettes and allows
      expression of the genes.

PMID- 9155173
TI  - [Mechanisms of endogenous drug resistance acquisition by spontaneous chromosomal
      gene mutation].
AB  - Endogenous resistance in bacteria is caused by a change or loss of function and
      generally genetically recessive. However, this type of resistance acquisition are
      now prevalent in clinical setting. Chromosomal genes that afford endogenous
      resistance are the genes correlated with the target of the drug, the drug
      inactivating enzymes, and permeability of the molecules including the
      antibacterial agents. Endogenous alteration of the drug target are mediated by
      the spontaneous mutation of their structural gene. This mutation provides much
      lower affinity of the drugs for the target. Gene expression of the inactivating
      enzymes, such as class C beta-lactamase, is generally regulated by regulatory
      genes. Spontaneous mutations in the regulatory genes cause constitutive enzyme
      production and provides the resistant to the agent which is usually stable for
      such enzymes. Spontaneous mutation in the structural gene gives the enzyme extra
      spectrum substrate specificity, like ESBL (Extra-Spectrum-beta-Lactamase).
      Expression of structural genes encoding the permeability systems are also
      regulated by some regulatory genes. The spontaneous mutation of the regulatory
      genes reduce an amount of porin protein. This mutation causes much lower influx
      of the drug in the cell. Spontaneous mutation in promoter region of the
      structural gene of efflux protein was observed. This mutation raised the gene
      transcription and overproduced efflux protein. This protein progresses the drug
      efflux from the cell.

PMID- 9155174
TI  - [The quantitative expression of susceptibility and its clinical significance].
AB  - As for the methods for dilution antimicrobial susceptibility tests, the results
      are expressed quantitatively as minimum inhibitory concentration (MIC). MICs are
      useful index not only for the choice of antibiotics to the treatment of
      infectious diseases but the exact detection of resistant strains. Recently, the
      study for the mechanism of the bacterial resistance to antibiotics were made
      remarkable progress, the important point of MICs in the combination of species
      and antibiotics were become clear. To improve the quality of the susceptibility
      tests, it is necessary to come into wide use of the dilution antimicrobial
      susceptibility tests instead of the disk susceptibility tests which are popular
      in JAPAN.

PMID- 9155175
TI  - [Genetics of multiresistant MRSA].
AB  - Since the introduction of methicillin, methicillin resistant S. aureus (MRSA) was
      appeared in 1961 in England. MRSA produces specific penicillin-binding protein
      PBP2' which shows very low affinity to most of beta-lactam antibiotics. The
      region around mecA is called additional DNA or mec DNA and is thought to be
      extraspecies origin. From the study of mec DNA, it was revealed that there were
      three types of mec DNA. In the case of mec DNA of N315, a transposon Tn554 which
      encoded erythromysin and spectinomycin resistance, and a plasmid pUB110 which
      encoded resistance to kanamycin, tobramycin, and bleomycin were integrated. MRSA
      became resistant to many antibiotics during a few years which were effective at
      the time of introduction, such as, carbapenems, new quinolones, and minocycline.
      MRSA has changed their properties by obtaining resistance-genes or generating
      mutations on its chromosomal DNA.

PMID- 9155176
TI  - [Regulation mechanism of glycopeptide resistance expression].
AB  - The glycopeptide antibiotics have been used to treat severe infections caused by
      pathogenic Gram- positive bacteria since their discovery in the 1950s. However,
      resistance is now emerging and spreading among enterococci. The mechanism of
      resistance is the synthesis of a modified cell-wall precursor, terminating in D
      lactate with a lower affinity for the glycopeptides. Three glycopeptide
      resistance phenotype (VanA, VanB and VanC) have been distinguished on the basis
      of the level and inducibility of the resistance to vancomycin and teicoplanin.
      Especially, most attention has been focused on VanA resistance because of a high
      level resistance. VanA-resistance has been associated with five genes (vanR,
      vanS, vanH, vanA, vanX) on the transposon Tn 1546, which usually resides on a
      plasmid. Synthesis of VanH, VanA and VanX is regulated at the transcriptional
      level by the VanR-VanS two-component regulatory system. The VanH dehydrogenase
      and the VanA ligase, which is D-Ala-D-Ala ligase of altered substrates
      specificity, catalyze the synthesis of the depsipeptide D-alanyl-D-lactate. The
      VanX dipeptidase hydrolyzes the dipeptide D-alanyl-D-alanine produced by the host
      ligase.

PMID- 9155177
TI  - [Penicillin-resistant mechanisms of Streptococcus pneumoniae].

PMID- 9155178
TI  - [Appearance of extended-spectrum beta-lactamases].
AB  - Extended-spectrum beta-lactamases (ESBLs) are enzymes which hydrolyze broad
      spectrum beta-lactam antibiotics by expanding the substrate spectra into the so
      called anti-beta-lactamase beta-lactams such as oxyimino-cephalosporins,
      cephamycins, oxacephems, carbapenems and monobactams, conferring resistance to
      many kinds of beta-lactams on pathogenic bacteria. Recently, ESBLs have been
      demonstrated from various types of beta-lactamases phylogenetically belonging to
      the molecular class, A, B, C, or D. The genes coding for ESBLs are chromosome- or
      plasmid-mediated and some of them have developed by point or insertion mutations
      in the parental genes coding for the narrow-spectrum beta-lactamase. If the genes
      are plasmid-mediated, the dissemination among various species of pathogenic
      bacteria would cause hospital-acquired infections by ESBL-producing bacteria.

PMID- 9155179
TI  - [Mechanisms of bacterial resistance to beta-lactams by beta-lactamases].
AB  - The beta-lactamases are bacterial enzymes that inactivate beta-lactam antibiotics
      by catalyzing the hydrolysis of the amide group of the beta-lactam ring. They are
      the source of much bacterial resistance to those antibiotics. Structural studies
      on the enzymes, i.e., penicillinases and cephalosporinases, are now well-advanced
      and the up-to-date knowledge of this research field were explained together with
      the proposed mechanism of beta-lactam hydrolysis by a cephalosporinase. After the
      introduction of the beta-lactamase-stable beta-lactams such as oxyimino
      cephalosporins, R plasmid-mediated penicillinases and a chromosomal
      cephalosporinase have been found to be adapted to the new drugs by mutation. The
      characteristics of the mutant beta-lactamases and their importance in the
      bacterial resistance to the new beta-lactams were explained.

PMID- 9155180
TI  - [Biochemical and genetic mechanisms for bacteria to acquire aminoglycoside
      antibiotic resistance].
AB  - Aminoglycoside (AG)-modifying enzymes are the major biochemical basis for the AG
      resistance of clinically-occurring bacteria. Recent AG resistance profiles can be
      characterized by the involvement of AAC(6') in combination with other modifying
      enzymes in Gram negative bacteria. AAC(6')/APH(2") in Staphylococcus aureus is
      also remarkable. Genetic basis for the emergence or alteration of AG resistance
      profiles includes point mutations in the regulatory region or specific sites of
      the coding region of AG-modifying enzyme genes, and rearrangement of the genes
      caused by transposon and/or integron. In addition, semisynthetic AG antibiotics
      such as amikacin, arbekacin (ABK) and isepamicin were also reviewed for their
      stability to AG-modifying enzymes. ABK that has been widely used as an anti-MRSA
      drug in Japan is distinct from the other AGs because its monoacetylated
      derivatives (3"-N-acetylABK and 2'-N-acetylABK) by AG acetyltransferases, AAC(3)
      and AAC(2'), respectively, retain clear antibiotic activities. Based on this
      novel aspect and the lack of modification sites for APH(3') and ANT(4'), ABK
      should be regarded as the most refractory AG for bacteria to acquire resistance.

PMID- 9155181
TI  - [Resistance to macrolides].
AB  - Resistance mechanisms to macrolide antibiotics involving lincosamide and
      streptogramin type B antibiotics were described in bacteria. Phenotype in the
      resistant microorganism is generally observed as one of two characteristics,
      i.e., decrease of intracellular macrolide-accumulation and inactivation of the
      drugs. The former phenotypic resistance results from one of three mechanisms: (1)
      mono- or di- methylation of a specific adenine residue in 23 S ribosomal RNA and
      (2) impaired uptake and (3) enhanced efflux of the antibiotics. The latter is
      caused by one of two mechanisms: (1) degradation of the drugs by a hydrolytic
      enzyme such as an esterase and (2) drug modification by one of enzymes such as
      nucleotidyl- and phospho- transferases.

PMID- 9155182
TI  - [Bacterial resistance mechanisms for tetracyclines].
AB  - Tetracycline resistance mechanism is unique in bacterial resistance mechanisms
      because of being mainly based on the drug efflux except for the ribosomal
      protection mechanism in some tetracycline-resistant Gram-positive bacteria.
      Tetracycline efflux proteins such as Tet(B) and Tet(C) of Gram-negative bacteria
      are estimated to have 12-membrane-spanning structure common to the major
      facilitator family transporters. We experimentally proved the 12-membrane
      spanning structure of Tet(B) by site-directed chemical labeling. On the other
      hand, the tetracycline efflux proteins such as Tet(K) and Tet(L) of Gram-positive
      bacteria are estimated to have 14-membrane-spanning structure. We first presented
      the experimental evidence for the 14-spanning structure of Tet(K) based on the
      Tet(K)-PhoA fusion protein analysis. Another mechanism of tetracycline resistance
      is a ribosomal protection encoded by tet(M) and let(O). These genes encode the
      elongation factor(EF-Tu or EF-G)-like protein, whereas the molecular mechanism of
      the resistance has not yet been revealed.

PMID- 9155183
TI  - [Mechanisms for the development of quinolone resistance].
AB  - New fluoroquinolones have potent and broad antimicrobial activity and spectra,
      respectively, against gram-positive and -negative bacteria including P.
      aeruginosa. As a result of their frequent use, bacterial resistance to the
      quinolones has gradually developed and limited their therapeutic efficacy in
      infections, especially, with P. aeruginosa, S. pneumoniae, S. aureus (especially
      MRSA), and N. gonorrhoeae. Bacterial resistance to the quinolones probably
      results from : 1) mutations with chromosomal genes of DNA gyrase or DNA
      topoisomerase in E. coli and S. aureus, 2) decreased permeability of the cell
      envelope through OmpF, porin-forming protein, in gram-negative bacteria, and 3)
      activation of active efflux-mediated permeability through the cell membrane
      protein, either NorA in S. aureus or Opr in P. aeruginosa. Proper use of the
      quinolones is also proposed to prevent emergence of the bacterial resistance.

PMID- 9155184
TI  - [Possibility of drug design of beta-lactam antibiotics effective for
      multiresistant gram-positive pathogens].
AB  - Since infectious diseases are caused by various bacteria and most of them are
      treated empirically, broad-spectrum antibiotics are required. To expand the
      spectrum, an imidazopyridazinium group and aminothiadiazole group were introduced
      to 3- and 7-side chain of cephem nucleus, respectively. The resulting compound,
      cefozopran, was able to permeate not only outer membrane of Pseudomonas
      aeruginosa but also envelope of gram-positive bacteria, which functioned as a
      barrier to antipseudomonal cephalosporins, and showed potent activity against
      wide variety of bacteria including those which produced a large amount of
      cephalosporinase and were resistant to third-generation cephalosporins. In spite
      of the broad antibacterial spectrum, cefozopran only weakly affected
      gastrointestinal flora of mice and prevented colonization by MRSA.

PMID- 9155185
TI  - [The possibility of drug design of quinolones effective for multiresistant gram
      positive pathogens].
AB  - Recently rapid increase in the emergence of multiresistant Gram-positive pathogen
      such as MRSA, penicillin resistant Streptococcus pneumoniae (PRSP), and
      vancomycin resistant Enterococcus (VRE). Whether quinolone antibacterial agent
      (quinolone) come to a promising drug or not for the treatment of these infectious
      diseases, it depend on an appropriate drug design of quinolones which have good
      toxicological and pharmacokinetic profile along with excellent antibacterial
      activities against these Gram-positive pathogens. In this chapter, we examine the
      possibility by following the history of the advances in quinolone research.

PMID- 9155186
TI  - [Development of beta-lactamase inhibitors].
AB  - The proportion of beta-lactamase producing bacteria in each species of clinical
      isolates is high (over 90%) in these years. According to the survey of bacterial
      resistance in 1995, higher proportion of resistant bacterial species against
      ampicillin, piperacillin (PIPC), cefazolin, cefotiam was observed. To overcome
      the bacterial resistance against these beta-lactam antibiotics, we have made a
      development of beta-lactamase inhibitor and its combination antibiotic. New beta
      lactamase inhibitor, tazobactam (TAZ) showed strong inhibitory activity against
      various kinds of beta-lactamases including cephalosporinases. The combination
      antibiotic, TAZ/PIPC(TAZ combined with PIPC by 1 to 4) showed stronger
      antibacterial activity than PIPC against beta-lactamase producing stains. And
      also the activity of TAZ/PIPC was superior to PIPC in the mixed bacterial
      infection model in mouse. The in vitro and in vivo frequency of emergence of
      resistant bacteria from Enterobacteriacae treated with TAZ/PIPC was lower than
      that of PIPC or ceftazidime (CAZ). By these data, combined antibiotics with beta
      lactamase inhibitor was effective to resolve the problems of bacterial
      resistances caused by beta-lactamases.

PMID- 9155187
TI  - [Molecular design of anti-MRSA drugs].
AB  - The true nature of resistance of methicillin-resistant Staphylococcus aureus
      (MRSA) is penicillin-binding protein 2' (PBP2'). Affinities of almost all beta
      lactam antibiotics to PBP2' were very low. Therefore, MRSA which produces PBP2'
      shows resistance to all beta-lactam antibiotics. However, PBP2' has a different
      affinity to each beta-lactam antibiotic. For this reason, we thought that some
      derivatives of beta-lactam compounds could have high affinity to PBP2'.
      Accordingly, we developed cephem compounds which are more stabile and safe than
      previous penicillin and carbapenem compounds. Firstly, we investigated the side
      chain at C-7 position on 2-thioisocephem skeletal. Hydroxyimino-aminothiazol at C
      7 position on 2-thioisocephem skeletal had the strongest activity against MRSA.
      Secondly, we investigated the linkage styles at C-3 position on 2-thioisocephem
      skeletal which were methylene, vinyl, and propylene. The compound of vinyl
      linkage style at C-3 position on 2-thioisocephem skeletal showed high activity
      against MRSA. Finally, we investigated 1-thiocephem, 2-thioisocephem, and 2
      oxaisocephem as cephem-skeletals. Simultaneously, we studied C-3 linkage styles
      which were methylene, vinyl, and propylene. From these results, we found out that
      the compound of hydroxyiminoaminothiazol at C-7 position and vinyl linkage style
      at C-3 position on 1-thiocephem skeletal has superb activity against MRSA.

PMID- 9155188
TI  - [Approval of HIV protease inhibitors as the AIDS therapeutics of next
      generation].
AB  - The long-term usages of reverse transcriptase inhibitors as anti-HIV drugs have
      induced serious side effects and emergence of resistant viruses. To overcome
      these problems, combination therapies are expected to be effective. Under such
      circumstances, HIV protease inhibitors have been rationally designed and
      synthesized based on the substrate transition state concept. HIV protease
      inhibitors act at the exact point in the life cycle of HIV, exhibited efficacy in
      the clinical trials and have been approved with high expectation. The
      introduction of anti-HIV drug with novel action mechanism evoked a new dramatic
      movement in the combination therapy of AIDS.

PMID- 9155189
TI  - [Human gene therapy for lung cancer].
AB  - Lung cancer is one of the leading causes of cancer death in the world. The high
      mortality rate for lung cancer results from the absence of standard therapeutic
      strategies. Recent advances in molecular biology have demonstrated that multistep
      genetic alterations are involved in the carcinogenesis of human lung cancer.
      Human gene therapy has become a reality with the development of effective
      techniques for delivering the gene to the target cells. The efficacy of gene
      therapy for various types of genetic disease now being evaluated in clinical
      trials. These findings led us to develop a novel gene therapeutic strategy for
      human lung cancer that could either inhibit the oncogene expression or replace
      the tumor suppressor gene by using recombinant, replication-defective viral
      vectors. The article reviews recent highlights in this rapidly evolving field.

PMID- 9155190
TI  - [Causes, diagnosis, and treatment of anemia in the elderly].
AB  - Healthy elderly people are mildly anemic peripheral blood data on 3,583 healthy
      elderly people (1,590 men and 1,993 women aged 65 years or older) from among
      those undergoing medical examinations at our hospital in the 8 years from 1988 to
      1995 were compiled into 5-year age groups. For both men and women the mean values
      of red blood cell count, hemoglobin, and hematocrit were slightly lower among
      older subjects. The main causes of this apparent reduction may be a decrease in
      the number of hematopoietic stem cells and regression of the hematopoietic
      microenvironment. Observation of arteries in specimens of hematopoietic bone
      marrow obtained from the spines of elderly people showed arteriosclerotic changes
      such as greater hypertrophy of the media than of the intima, and adventitial
      fibrous hypertrophy. The number of venous sinuses was low and the amount of
      adipose tissue was high compared to the bone marrow of younger people. The cell
      density and the ratio of hematopoietic tissue to fat tended to be lower in older
      subjects. The number of erythroid burst-forming units formed after 14 days in
      culture medium containing erythropoietin was 28 +/- 19 in 32 healthy elderly
      people, which was significantly lower than the number in 30 young people 54 +/-
      30, (p < 0.005). The value for erythroid colony-forming units was 170 +/- 67 in
      eight healthy people, which was much lower than in young people, 276 +/- 54. In
      the elderly subjects, the plasma iron disappearance time (PIDT/2) was 60-80 min
      (mean: 71.9 min), which was similar to that in the young, but the percent red
      cell iron utilization was 67.6%-84.9% (mean: 79.7%), which was slightly lower
      than in younger people. When the diagnostic criterion for anemia in the elderly
      was set at a hemoglobin value of 11.0 g/ dl, about 13% of outpatients who came to
      our Geriatrics department were found to have anemia, and in most of them the
      anemia had resulted from another disease. In conclusion, anemia in the elderly is
      likely to be affected by reduction in the function of various organs and by the
      decreased reserves associated with aging. The causes of anemia are complex and
      diagnosis is often difficult. The present article gives a general outline of the
      diagnosis and treatment of common types of primary and secondary anemia in the
      elderly.

PMID- 9155191
TI  - [Bronchial asthma in the elderly: special reference to pathogenesis and
      treatment].

PMID- 9155192
TI  - [Lipoprotein(a) as a risk factor for cardiovascular disease in elderly patients
      with diabetes].
AB  - Lipoprotein(a) (Lp(a)) is an independent risk factor for cardiovascular diseases
      in non-diabetic people, but few studies have been done in diabetic patients. To
      investigate whether Lp(a) is a risk factor for cardiovascular disease in elderly
      people with diabetes, we examined the association of Lp(a) and serum lipid levels
      (total cholesterol: TC; triglycerides: TG; and high-density lipoprotein
      cholesterol: HDL-c) with the incidence of coronary artery disease and
      cerebrovascular disease. We studied 354 outpatients(131 men and 223 women, 60-97
      years of age) with non-insulin-dependent diabetes mellitus. The mean
      concentration of Lp(a) was 21.1 +/- 19.6 mg/dl and the median was 14.0 mg/dl. The
      Lp(a) concentration did not correlate significantly with age or with sex, but it
      did correlate significantly with TC (r = 0.152, p < 0.05) and with the level of
      apoprotein B (r = 0.168, p < 0.05). The incidence of cerebrovascular disease was
      significantly higher in patients with high concentrations of Lp(a) (> or = 30 mg/
      dl) than in those with low concentrations (< 30 mg/ dl). Multivariate logistic
      regression analysis revealed that male sex, hypertension, a high level of HbA1c,
      a low level of HDL, and a high level of Lp(a) were independent risk factors for
      cerebrovascular disease. The incidence of coronary artery disease tended to the
      higher in those with high concentrations of Lp(a) (> or = 30 mg/dl). However,
      multivariate logistic regression analysis revealed no significant correlation
      between Lp(a) concentration and the incidence of coronary artery disease. We
      conclude that a high concentration of Lp(a) is an independent risk factor for
      cerebrovascular disease in elderly patients with diabetes.

PMID- 9155193
TI  - [Parkinsonism and postoperative complications in the elderly].
AB  - The risk factors for postoperative morbidity and mortality in elderly patients
      with Parkinsonism after gastrointestinal surgery were evaluated by univariate and
      multivariate analyses in comparison to those of patients with cerebrovascular
      disease and to those of patients with no comorbid condition. Data were obtained
      on 36 patients with Parkinsonism (PK), 77 with cerebrovascular disease (CVD) and
      120 with no comorbid condition (ND). All data were adjusted for age, sex and
      operative procedure. The postoperative morbidity rate was highest in the PK group
      (77.8%), followed by the CVD group (70.1%), and both differed significantly from
      the rate of the ND group (32.5%). Gastrointestinal and pulmonary complications
      and delirium were the major postoperative complications, and were significantly
      more common in the PK group than in the ND group. Patients in the PK group had
      the longest postoperative hospital stay, followed by those in the CVD and ND
      groups; the differences were significant between the PK and ND groups and between
      CVD and ND groups. The PK group had the highest operative and hospital mortality
      rates, and they differed significantly from the ND group. Hayashi's second method
      of quantification was used to assess the risk factors for postoperative death.
      The highest partial correlation coefficient was that found for postoperative
      pulmonary complication. We conclude that we should pay close attention to
      postoperative respiratory management, particularly in elderly patients with
      Parkinsonism, to prevent pulmonary complications and reduce postoperative
      mortality.

PMID- 9155194
TI  - [Apolipoprotein E epsilon 4 allel frequencies, plasma alpha 2-macroglobulin and
      plasminogen activator inhibitor 1 levels in residents of a rural area in Gunma
      prefecture].
AB  - The apolipoprotein E4 (apoE4) epsilon 4 allele is a major riks factor for
      Alzheimer's disease. However, epsilon 4 is neither a necessary nor a sufficient
      condition for the development of this disease, and many cognitively healthy
      elderly people carry the epsilon 4 allele. To look for age-dependent changes in
      epsilon 4 allele frequencies in the general population, we measured the
      frequencies in 141 normal healthy residents of a mountainous rural area in north
      west Gunma prefecture. Levels of cholesterols in plasma were measured and their
      relation to apoE genotypes was studied. We also measured the levels of alpha 2
      macroglobulin (alpha 2M) and plasminogen activator inhibitor 1 (PAI-1) in blood,
      and studied their relation to apoE genotypes. Because low-density lipoprotein
      receptor-related protein (LRP) binds apoE, alpha 2M, and PAI-1, it is of interest
      to see whether the alpha 2M and PAI-1 concentrations in blood differ between
      epsilon 4 carriers and non-carriers. ApoE allele frequencies were 0.05, 0.84, and
      0.11 for epsilon 2, epsilon 3, and epsilon 4, respectively. In both men and
      women, the frequency of epsilon 4 was lowest among those in the seventh decade of
      life. The frequency of epsilon 4 among octagenarians was high (0.17). Serum
      levels of total cholesterol and low-density lipoprotein cholesterol did not
      differ significantly between epsilon 4 carriers and non-carriers. The alpha 2M
      level in serum was higher in women than in men and was higher in older subjects
      than in younger subjects. Plasma PAI-1 levels were significantly higher in men
      than in women (Student's t-test, p = 0.0197). Neither alpha 2M levels nor PAI-1
      levels differed between epsilon 4 carriers and non-carriers, which suggests that
      the levels of these two proteins in blood do not reflect the status of LRP in
      individuals with various apoE genotypes. Studies that include data on life style
      and diet are necessary before we can conclude that rural life contributes to
      longevity in epsilon 4 carriers.

PMID- 9155195
TI  - [Lipid and lipoprotein profile of Japanese centenarians--high prevalence of hypo
      beta lipoproteinemia].
AB  - To study the relationship between lipids and longevity, we examined the level of
      serum lipids and apolipoproteins, and the susceptibility of low density
      lipoprotein (LDL) to oxidation of 45 centenarians (15 men, 30 women, mean age
      101.1 +/- 1.4) living in the Tokyo metropolitan area. The average levels of total
      cholesterol (TC), of LDL-C of high-density lipoprotein cholesterol (HDL-C), and
      of apolipoproteins A1 and B were significantly lower in centenarians than in
      healthy middle-aged controls. The frequency of hypobeta-lipoproteinemia (apoB <
      60 mg/dl) in centenarians was almost ten times as high as in controls. The time
      course of copper-mediated LDL, oxidation (assessed by monitoring 234 nm diene
      absorption (lag time)) did not significantly differ between the two groups.
      Analysis of LDL subfractions by non-denaturated gradient-gel electrophoresis
      showed a predominance of large, buoyant LDL particles (pattern A) in 75%, and a
      predominance of small dense LDL particles (pattern B) in 25% of centenarians. We
      also assessed activities of daily living (ADL) and cognitive function in the
      centenarians. Centenarians were divided into two groups according to the median
      ADL score, and were classified into five groups with a scale clinical dementia.
      In subjects with good ADL scores, the mean concentration of HDL-3-C was
      significantly higher than in those with poor ADL scores. Average levels of HDL-C
      were also significantly lower in subjects with moderate or severe dementia than
      in those with normal cognitive function. These findings suggest that centenarians
      have protective phenotypes of lipids and lipoproteins that protect them from
      atheroscierosis.

PMID- 9155196
TI  - [Development of a regimen comprehension scale].
AB  - Whether elderly patients can take prescription drugs as directed by a physician
      is often unclear. So elderly patients could receive adequate instruction
      regarding their medications, we developed a regimen comprehension scale (RCS)
      with simple questions regarding information on dosage and administration. This
      information was written on the outside of the paper bags in which the medications
      are usually dispensed. The subjects were 21 healthy volunteers (11 men and 10
      women, averaged age 38.3 +/- 11.2 years) and 17 inpatients (9 men and 8 women,
      averaged age 73.4 +/- 6.8 years). Five kinds of drugs, which differed with
      respect to dosage and administration were used. The subjects were questioned in
      an interview about taking the five drugs and their regimen comprehension was
      assessed with the RCS (maximum score: 10 points, lowest score: 10 points. Then
      regimen comprehension was classified into 4 grades: normal (10), caution needed
      (9 or 8), training needed (7 or 6), and assistance needed (5 or less). In
      addition, intelligence was tested with the revised version of Hasegawa's dementia
      scale (HDS-R). Eight of the 21 healthy volunteers (38%) and 13 of the 17 elderly
      patients (76%) misunderstood some aspects of the regimens written on the paper
      bags. The regimen comprehension was classified as "normal", "caution needed", and
      "training needed" in 13, 7, and 1 of the healthy volunteers, respectively, it was
      classified as "normal", "caution needed", "training needed", and "assistance
      needed" in 4, 4, 4, and 5 elderly patients, respectively. The five elderly
      patients classified as "assistance needed" were suspected to have dementia
      because they had scores on the HDS-R of 21 or less. A significant positive
      correlation (r = 0.797) was noted between scores on the HDS-R and on the RCS.
      When treating elderly patients with chronic disease (for example, hypertension)
      it is important to evaluate their regimen comprehension with an index such as the
      RCS to determine the need for medication counseling before the start of a
      medication regimen.

PMID- 9155197
TI  - [Cushing's syndrome due to small cell lung cancer with ectopic production of
      adrenocorticotropic and parathyroid hormone].
AB  - A 72-year-old man was admitted to our hospital because of a tumor-like shadow on
      a chest X-ray film. At the initial examination, he had clinical signs of
      Cushing's syndrome: moon face, central obesity, and hypertension. A computed
      tomographic scan of chest showed an abnormal shadow in the lung (5 x 6 cm) with
      involvement of the right paratracheal and anterior tracheal lymph nodes, and a
      right-sided pleural effusion. Small cell lung cancer (extended disease; T2N2M6
      stage IV) was diagnosed after a transbronchial biopsy. The concentrations of
      adrenocorticotropic hormone, cortisol, and parathyroid hormone in plasma were
      markedly elevated, and there was no circadian rhythm (336 pg/ml. more than 60.1
      micrograms ml. and 805 pg/ml, respectively). Fluid obtained by thoracentasis had
      malignant cells, and the levels of adrenocorticotropic hormone and parathyroid
      hormone in the effusion (1120 pg/ml and 1810 pg/ml, respectively) were higher
      than those in serum, which indicates that these hormones were produced by the
      tumor cells. The patient received chemotherapy and responded well, but he died of
      respiratory failure 26 months later. The response rate to chemotherapy in elderly
      patients with lung cancer is said to be comparable to that in younger patients,
      but treatment may be difficult because of poor performance status and diminished
      physical capacity. Although patients with lung cancer complicated by Cushing's
      syndrome have a poor prognosis, this patient survived for more than 2 years after
      the disease was diagnosed.

PMID- 9155198
TI  - [Successful treatment of heavy-chain disease with etoposide].
AB  - A 79-year-old man with marked hepatosplenomegaly and lymphadenopathy was admitted
      to the hospital. Analysis of serum protein resulted in the diagnosis of gamma
      chain disease (total protein 6.2 g/dl, M-protein positive, IgG 4150 mg/dl, IgG-Fc
      fragment positive). Specimens obtained by lymph node biopsies showed infiltration
      of plasmacytoid cells, which were stained with anti-IgG but not with anti-kappa
      or anti-lambda antibodies. The patient was given combination chemotherapy, but
      without effect. Then a regimen of long-term administration of low-dose etoposide
      was begun, and resulted in remission of the lymphadenopathy, hepatosplenomegaly,
      and abnormal IgG.

PMID- 9155199
TI  - [Hyperventilation syndrome in a very old woman].
AB  - A 92-year-old woman was admitted to our hospital due to hypertension, nausea,
      pain in the anterior part of the chest, epigastralgia, and tachypnea. During the
      initial examination of the patient in the emergency ward, she was very excited,
      howled, and both her hands were numb. Arterial blood gas analysis revealed a
      marked alkalemia (pH greater than 7.55) and hypocapnia (Pco2 24.1 mmHg). After
      paper bag re-breathing, the pH and Pco2 were within normal limits. Because there
      was no lesion in the lungs or the brain that would account for hyperventilation
      and convulsions, the attack was considered to be a manifestation of
      hyperventilation syndrome should be carefully considered in the differential
      diagnosis of disturbance of consciousness even in elderly patients.

PMID- 9155200
TI  - [Recent knowledge on fish pathogenic bacteria Aeromonas salmonicida, Listonella
      anguillara and Cytophaga columnaris, and their virulence factors].

PMID- 9155201
TI  - [Genetic basis for molecular epidemiology of MRSA].

PMID- 9155202
TI  - [Molecular biology of the GPI-anchored proteins].

PMID- 9155203
TI  - [Bacteriolytic enzymes produced by the staphylococci].

PMID- 9155204
TI  - [Chemical structure and biological activities of Porphyromonas gingivalis lipid
      A].

PMID- 9155205
TI  - [Host defense against mycobacterial infections--new strategies for combatting
      multidrug-resistant mycobacterial diseases].

PMID- 9155206
TI  - [Colonization of methicillin-resistant Staphylococcus aureus in the mouse
      intestinal tract].
AB  - Mice were infected intravenously with rifampicin-resistant strains selected out
      of methicillin-resistant Staphylococcus aureus (MRSA) strains and examined for
      colonization of these organisms in the intestinal tract. Three of four MRSA
      strains colonized in the cecum of more than 80% of the mice inoculated with
      approximately 10(7) cfu/mouse. The extent of colonization paralleled the lethal
      activity, which was inversely related to the methicillin resistivity: moderately
      resistant strains (MIC: 12.5 micrograms/ml) tended to show more potent
      pathogenicity than highly resistant ones (MIC: > or = 100 micrograms/ml).
      Distribution and localization of the organisms in the mice infected with a
      moderately resistant and highly pathogenic strain S. aureus 1-6 RFPr were studied
      by autobacteriography. Within one day after infection, colonies of the infecting
      organisms were distributed all over the body and were especially dense in the
      liver and spleen. On day 3, the organisms in the liver and spleen disappeared,
      while many colonies were observed in the intestinal tract. The organisms in the
      intestinal tract remained for 14 days after infection. In the autobacteriograms
      of the mice infected with Escherichia coli KC-14 RFPr, such persistency in the
      intestinal tract was not demonstrated. When viable cell counts of the cecum
      contents of the mice infected with S. aureus 1-6 RFPr (approximately 10(7)
      cfu/mouse) were made, the organisms were detected as early as 3 hr after
      infection and then gradually increased to more than 4 logs cfu/g on day 7. With
      E. coli KC-14 RFPr, a few colonies were detected transiently in the cecum
      contents of mice at an early stage infection, but the organisms did not increase
      and disappeared by day 3 after infection. These results show that the
      colonization in the mouse intestinal tract is a specific phenomenon to the S.
      aureus species including MRSA strains.

PMID- 9155207
TI  - [Studies on enrichment broth for verotoxin-producing Escherichia coli (VTEC)
      O157].
AB  - Growth of verotoxin-producing Escherichia coli (VTEC) O157 in conventionally
      recommended pre-enrichment broth media at different temperatures was evaluated.
      In addition, sensitivity of VTEC O157 isolates to several antibacterial drugs,
      which were added to the selective enrichment broth, was tested. All five isolates
      of VTEC O157 tested grew well in trypticase soy broth (TSB) at 36 degrees C and
      42 degrees C, while the growth of one isolate was markedly suppressed in TSB
      supplemented with cefixime (CFIX), potassium tellurite (PT), and vancomycin (TSB
      CTV) even at 36 degrees C. A significant growth suppression was also observed in
      three of the isolates cultured in novobiocin (NB)-supplemented modified EC broth
      (mEC-NB) at 42 degrees C. In mEC-NB after 24-hr incubation at 36 degrees C, the
      five VTEC O157 isolates grew well, although one isolate was slightly suppressed
      during the first 8 hours. Minimum growth inhibitory concentrations of CFIX, NB
      and PT for a total of 90 clinical and environmental isolates of VTEC O157 were
      all above the concentrations usually prescribed for mEC-NB and TSB-CTV. These
      findings suggest that mEC-NB and TSB-CTV should be used at 36 degrees C for
      growth of VTEC O157 and that use of a nonselective pre-enrichment broth medium
      (i.e. TSB) together with a selective one (i.e. TSB-CTV or mEC-NB) is necessary
      for successful isolation of VTEC O157 from various specimens.

PMID- 9155208
TI  - [Direct in situ PCR method for the detection of verotoxin-producing Escherichia
      coli].
AB  - Rapid detection of verotoxin-producing Escherichia coli at a single-cell level
      under an epifluorescence microscope without culturing processes was accomplished
      by using the direct in situ PCR technique. We used a DNA primer set for
      amplification of the slt-I and slt-II genes encoding respectively verotoxin 1 and
      2 (EVT and EVS primers). The bacterial cells were detected specifically by the
      HNPP (2-hydroxy-3-naphthoic acid-2'-phenylanilide phosphate)/Fast Red TR reaction
      technique. The direct in situ PCR with HNPP/Fast Red TR technique is applicable
      to the detection of verotoxin-producing bacteria with the slt-I or slt-II gene in
      not only Escherichia coli O157 but also VTEC of other serotypes.

PMID- 9155210
TI  - Folate, vitamin B12, and neuropsychiatric disorders.
AB  - Folate and vitamin B12 are required both in the methylation of homocysteine to
      methionine and in the synthesis of S-adenosylmethionine. S-adenosylmethionine is
      involved in numerous methylation reactions involving proteins, phospholipids,
      DNA, and neurotransmitter metabolism. Both folate and vitamin B12 deficiency may
      cause similar neurologic and psychiatric disturbances including depression,
      dementia, and a demyelinating myelopathy. A current theory proposes that a defect
      in methylation processes is central to the biochemical basis of the
      neuropsychiatry of these vitamin deficiencies. Folate deficiency may specifically
      affect central monoamine metabolism and aggravate depressive disorders. In
      addition, the neurotoxic effects of homocysteine may also play a role in the
      neurologic and psychiatric disturbances that are associated with folate and
      vitamin B12 deficiency.

PMID- 9155209
TI  - Evidence for the relationship of calcium to blood pressure.

PMID- 9155211
TI  - Adverse effects of high-calcium diets in humans.
AB  - While the National Institutes of Health Consensus Conference on Calcium has
      recommended that all elderly persons need calcium intakes of 1500 mg/day, it also
      recognizes that adverse effects of high-calcium diets may occur at intakes
      greater than 2000 mg/day. The purpose of this paper is to highlight adverse
      effects of high-calcium diets that could have a negative impact on health.

PMID- 9155212
TI  - Applying the stages-of-change model to dietary change.
AB  - The transtheoretical model of behavior change ("Stages of Change") was first
      proposed by Prochaska and DiClemente 14 years ago. It was originally developed by
      observing smokers who were planning or attempting to give up smoking. It has
      since been applied to behaviors other than smoking, and several recently
      published papers have examined its application in the area of dietary change. The
      complexity of dietary change, however, has made it more difficult to apply the
      model in this area. Studies applying the model to diet have differed in terms of
      the aspect of diet being examined, as well as the staging algorithms and dietary
      assessment methodology used. Such differences in methodology have led to variable
      results and have made it difficult to interpret results obtained. This review
      summarizes the studies in this area and makes recommendations for future
      research.

PMID- 9155213
TI  - Nutrition and liver disease.
AB  - Although the normal liver has considerable ability to regenerate, advanced liver
      disease can significantly reduce this ability. In compensated liver disease, all
      efforts should be made to maintain nutrition status. In decompensated liver
      disease, symptoms of decompensation may require therapeutic dietetic
      intervention. Early nutrition assessment and dietetic intervention in the
      management of malnutrition, ascites, encephalopathy, and esophageal varices are
      mandatory and have shown reduced morbidity and mortality in these patients.

PMID- 9155214
TI  - Creatine is an ergogen for anaerobic exercise.
AB  - Throughout history, athletes have searched for performance-enhancing agents.
      Recently, creatine (N-[aminoiminomethyl]-N-methyl glycine) has been marketed as
      an ergogenic dietary supplement. There appears to be scientific merit to the
      claim that creatine is ergogenic when taken in large amounts. However, several
      issues regarding its use need to be addressed.

PMID- 9155215
TI  - Nutrition and Alzheimer's disease.
AB  - Alzheimer's disease is no longer considered an inevitable consequence of the
      aging process. The etiology is complex, involving several genes and possible
      environmental factors. Nutrition support is important in the treatment of people
      with Alzheimer's disease.

PMID- 9155216
TI  - The nutrition transition: new trends in the global diet.
AB  - Analyses of economic and food availability data for 1962-1994 reveal a major
      shift in the structure of the global diet marked by an uncoupling of the classic
      relationship between incomes and fat intakes. Global availability of cheap
      vegetable oils and fats has resulted in greatly increased fat consumption among
      low-income nations. Consequently, the nutrition transition now occurs at lower
      levels of the gross national product than previously, and is accelerated further
      by high urbanization rates. Data from Asian nations, where diet structure is
      rapidly changing, suggest that diets higher in fats and sweeteners are also more
      diverse and more varied. Given that preferences for palatable diets are a
      universal human trait, fat consumption may be governed not by physiological
      mechanisms but by the amount of fat available in the food supply. Whereas
      economic development has led to improved food security and better health, adverse
      health effects of the nutrition transition include growing rates of childhood
      obesity. The implications of these trends are explored.

PMID- 9155217
TI  - Food fortification in the United States.
AB  - Formulas for the fortification of nutrients have remained essentially unchanged
      for the half-century in which the U.S. government has had a fortification policy
      in place. During that period, the classical micronutrient deficiencies have
      disappeared, but changes in the U.S. food supply have occurred and concerns about
      adequate intakes of other micronutrients have emerged. In 1974 the Food and
      Nutrition Board published its "Proposed Fortification Policy for Cereal Grain
      Products." Of the six fortification endorsement conditions outlined in the policy
      statement, three do not meet the stated criteria or today's needs. New approaches
      to address this situation are proposed.

PMID- 9155218
TI  - The impact of disease states as a modifying factor for nutrition toxicity.
AB  - Acquired kidney and liver diseases are relatively common diseases that can raise
      the potential for nutrient intoxication. For example, high-protein diets increase
      glomerular blood flow and the blood pressure gradient across the glomerular
      capillary wall in the kidney, which can result in injury to membranes. Likewise,
      the liver can increase nutrient intoxication because it is involved in the
      intermediary metabolism of many nutrients, serves as the storage organ for many
      nutrients, and is important in the biotransformation and excretion of nutrients.
      In this paper, vitamin A serves as an example to illustrate how kidney disease
      and liver disease can increase a single nutrient's toxicity.

PMID- 9155219
TI  - A dietary intervention trial for nutritional management of cardiovascular risk
      factors.
AB  - A multicenter clinical trial was performed in 560 patients to assess the
      effectiveness of a prepackaged diet plan compared with self-selected American
      Heart Association Step 1 and Step 2 diets in lowering risk factors for
      cardiovascular disease in patients with mild to moderate disease. The results of
      the 10-week intervention study indicate that diets meeting the current
      recommendations for healthful diets significantly lower biochemical risk factors
      for cardiovascular diseases. Although the prepackaged dietary program achieved
      greater patient compliance in meeting dietary goals in the free-living condition
      compared with the self-selected diet, the long-term outpatient compliance with
      these diets needs further study. It is also unclear what role prepackage diets
      will play in the overall dietary management of patients at risk for
      cardiovascular disease.

PMID- 9155220
TI  - Food poisoning, listeriosis, and febrile gastroenteritis.
AB  - Outbreaks of foodborne disease owing to contamination with Listeria monocytogenes
      bacteria have usually been associated with the development of severe invasive
      disease. A recent report has provided clear documentation showing that outbreaks
      of L. monocytogenes also present as gastroenteritis and fever. Further studies of
      this foodborne organism are needed to determine its infectious dose and the
      characteristics of the host that are associated with noninvasive febrile
      gastroenteritis.

PMID- 9155221
TI  - Childhood nutrition and adult cardiovascular disease.

PMID- 9155222
TI  - Early determinants of immunocompetence.

PMID- 9155223
TI  - Human variation in body mass: evidence for a role of the genes.

PMID- 9155224
TI  - Long-term fetal programming of body composition and longevity.

PMID- 9155225
TI  - Antioxidants and human disease: a general introduction.

PMID- 9155226
TI  - Antioxidant vitamins and cardiovascular disease.

PMID- 9155227
TI  - Effects of vegetarian diets on aging and longevity.

PMID- 9155228
TI  - Nutrition and senescence.

PMID- 9155232
TI  - What's new about an old disease?

PMID- 9155233
TI  - The Objective Structured Clinical Examination (OSCE) in the clinical clerkship:
      an overview.
AB  - The Objective Structured Clinical Examination (OSCE) for student assessment is
      well established, with an extensive body of research documenting that this is a
      valid means to assess clinical skills that are fundamental to the practice of
      medicine. The OSCE consists of a circuit of stations which tests a range of
      skills and learning to assess undergraduate medical students. A well-constructed
      OSCE provides important information about candidate performance and the quality
      of training. It is used at the University of South Dakota School of Medicine
      (USDSM) in assessment of third year medical students during their Obstetrics
      Clerkship, and as a teaching tool in the Pediatric Clerkship. On August 10, 1996,
      the USDSM administered an OSCE for the first time to third year medical students.
      The purpose of this article is to present state of the art information about
      setting up OSCE based on our recent experience and to provide practical examples
      of OSCE questions which can be addressed in the clinical setting. The narrative,
      references and examples give guidelines for the preparation of OSCE testing. The
      OSCE provided a standardized way of assessing clinical competence. Both students
      and faculty were very satisfied with the examination, and felt that the material
      tested was relevant and appropriate. The OSCE process does serve to identify
      areas of weakness in the curriculum and/or teaching methods, and thus can serve
      as a mechanism to improve educational effectiveness.

PMID- 9155234
TI  - The dosage of immunoglobulin recommended for household contacts of cases of
      hepatitis A.

PMID- 9155235
TI  - Assessment of human risks from exposure to low toxicity occupational dusts.
AB  - Recent animal studies have demonstrated three separate and distinct mechanisms by
      which low toxicity dusts can cause important chronic pulmonary effects; through
      overloading of clearance mechanisms, through increased toxicity associated with
      ultrafine particle size or by increasing the toxicity of known carcinogens in
      mixed exposures. The problem to be addressed is how the pathogenicity to man of
      various airborne dusts should be evaluated, when epidemiological evidence is
      often insufficient, and the reliability of extrapolation of quantitative risks
      from animals to man is not established. In this paper we examine the feasibility
      of evaluating the likely human risks of low toxicity dusts by: (1) semi
      quantitative comparisons of the ability of various dusts, in animal studies, to
      cause overload of clearance and resulting inflammation and fibrosis; (2)
      postulating that these relativities apply quantitatively to human risks; and (3)
      estimating approximate human risks by comparisons with reference dusts for which
      adequate animal and human data are available. Such a decision-making framework
      appears feasible, provided: (1) comparable and quantitative methods are used
      consistently in animal studies for the measurement of impairment of clearance
      leading to overload and resulting inflammation and fibrosis; (2) the quantitative
      relationships between impairment of clearance leading to overload, and resulting
      inflammation and fibrosis, can be defined adequately in animals for various
      dusts; (3) the particle size distributions, including those in the ultrafine
      range, for dusts to which animals and/or humans are exposed, are taken into
      account (or are comparable); (4) at least two reference dusts with well
      documented activities spanning the range of toxicity can be identified; and (5)
      the reliability of the predictions of human pathogenicity of a sample of other
      dusts is tested, in toxicological studies and by observation in humans. Some
      possible candidate reference and test dusts are identified.

PMID- 9155236
TI  - A collaborative European study of personal inhalable aerosol sampler performance.
AB  - Following the adoption of new international sampling conventions for inhalable,
      thoracic and respirable aerosol fractions, a working group of Comite Europeen de
      Normalisation (CEN) drafted a standard for the performance of workplace aerosol
      sampling instruments. The present study was set up to verify the experimental,
      statistical and mathematical procedures recommended in the draft performance
      standard and to check that they could be applied to inhalable aerosol samplers.
      This was achieved by applying the tests to eight types of personal inhalable
      aerosol sampler commonly used for workplace monitoring throughout Europe. The
      study led to recommendations for revising the CEN draft standard, in order to
      simplify the tests and reduce their cost. However, some further work will be
      needed to develop simpler test facilities and methods. Several of the samplers
      tested were found to perform adequately with respect to the inhalable sampling
      convention, at least over a limited range of typical workplace conditions. In
      general the samplers were found to perform best in low external wind speeds,
      which are the test conditions thought to be closest to those normally found in
      indoor workplaces. The practical implementation of the CEN aerosol sampling
      conventions requires decisions on which sampling instruments to use, estimation
      of the likely impact that changing sampling methods could have on apparent
      exposures, and adjustment where necessary of exposure limit values. The sampler
      performance data obtained in this project were affected by large experimental
      errors, but are nevertheless a useful input to decisions on how to incorporate
      the CEN inhalable sampling convention into regulation, guidance and occupational
      hygiene practice.

PMID- 9155237
TI  - Airway symptoms among house painters in relation to exposure to volatile organic
      compounds (VOCS)--a longitudinal study.
AB  - The increased use of water-based paint (WBP) for indoor application during the
      last decade has drastically changed the exposure conditions for Swedish house
      painters. WBP has a lower emission of volatile organic compounds (VOCs) than
      solvent-based paint (SBP), but contains more reactive compounds, such as
      biocides, glycol ethers, and other high molecular solvents. The aim of this study
      was to compare the incidence of airway symptoms and self-reported asthma in house
      painters with a different degree of use of WBP and SBP. The incidence of seven
      general airway symptoms, and three work-related symptoms, was analysed by means
      of a self-administered questionnaire, in a cohort of 207 house painters followed
      from 1989 to 1992. Different airway symptoms were compared with clinical
      information obtained by a methacholine challenge test and dynamic spirometry in a
      selected subgroup of 44 painters. Information on the degree of use of SBP and WBP
      was used to estimate the total exposure to volatile organic compounds (TVOC) for
      each individual. In total, 175 men in the cohort worked as painters during the
      study period. No increase of asthma or respiratory symptoms was observed among
      those 50 painters with a pure exposure to WBP (estimated TVOC 1-3 mg m-3). Most
      painters (N = 125) had a mixed exposure to SBP and WBP, the main source of the
      TVOC being the limited use of SBP. WBP was perceived as less irritative than SBP,
      but complaints on airway irritation from WBP increased during the study period.
      The most pronounced increase of airway irritation in relation to both SBP and
      WBP, was observed among those 35 painters with the highest solvent exposure
      (estimated TVOC 100-380 mg m-3). An increase of respiratory symptom index and
      shortness of breath, in relation to estimated TVOC exposure was also observed.
      Selection effects were detected. Painters leaving their job during the study
      period had more non-specific hyper-reactivity symptoms, and more airway
      irritation from WBP, as compared to painters remaining at their occupation. Our
      study indicates that VOC emissions from SBPs may contribute to the development of
      respiratory symptoms and airway irritation. We found no increase of respiratory
      symptoms among painters exposed only to WBPs. There were, however, indications
      that VOC exposure from WBPs may cause airway irritation in some subjects. Because
      of selection effects, cross-sectional studies on respiratory symptoms in relation
      to occupational exposure to paint emissions may be inconclusive.

PMID- 9155238
TI  - Exposure to soluble nickel in electrolytic nickel refining.
AB  - Past and present exposure to nickel was studied in an electrolytic nickel
      refinery, where an increased incidence of nasal cancer had been reported, using
      nickel analyses in air, blood and urine. Genotoxic effects were studied using
      analysis of micronuclei from acridine orange-stained smears from the buccal
      mucosa of the workers. Workers used respirators or masks in tasks where the
      exposure was expected to be high. Inside the mask, nickel concentrations were 0.9
      2.4 micrograms m-3 in such tasks. In those tasks where masks were not used,
      nickel concentrations in the breathing zone were 1.3-21 micrograms m-3. Air-borne
      nickel concentrations (stationary sampling) varied between 230 and 800 micrograms
      m-3 in 1966-1988 with no systematic change; thereafter lower concentrations (170
      460 micrograms m-3) have been observed. After-shift urinary concentrations of
      nickel were 0.1-2 mumol l-1; they showed no correlation with nickel
      concentrations in the air. Concentrations of nickel in the urine were still
      elevated after a 2-4 week vacation. The frequency of micronucleated epithelial
      cells in the buccal mucosa of nickel refinery workers was not significantly
      elevated by comparison with referents. No relationship was observed between
      micronucleus frequencies and levels of nickel in air, urine or blood.

PMID- 9155239
TI  - Occupational exposure to nickel salts in electrolytic plating.
AB  - An occupational hygiene survey was made in 38 nickel plating shops in Finland and
      exposure to nickel was studied by means of biological measurements and, in three
      shops, by using air measurements. The average after-shift urinary nickel
      concentration of 163 workers was 0.16 mumol l.-1 (range 0.001-4.99 mumol l.-1).
      After the 1-5 week vacation the urinary nickel concentration was higher than the
      upper reference limit of non-exposed Finns indicating that a part of water
      soluble nickel salts is accumulated in the body. Urinary nickel concentrations in
      the shops considered clean in the industrial hygiene walk-through were not
      different from those observed in the shops considered dirty. The correlation
      between the concentrations of nickel in the air and in the urine was low, and the
      amount of nickel excreted in the urine exceeded the calculated inhaled amounts,
      indicating exposure by other routes such as ingestion.

PMID- 9155240
TI  - Exposure assessment of airborne microorganisms by fluorescence microscopy and
      image processing.
AB  - The purpose of this study was to improve the exposure assessment of airborne
      microorganisms by means of image processing of fluorescence microscopy images.
      This technique reduces the analysis time and also offers the opportunity to
      measure the size distribution of the microorganisms. We developed and implemented
      an automatic focusing procedure in order to count and size evaluate the
      microorganisms in the sample. However, automatic focusing was not possible if
      there were any impurities such as larger particles present. Therefore, manual
      focusing of the microscope had to be applied in connection with automatic
      counting and size evaluation when assessing the exposure of workers handling
      materials containing microorganisms, for example. This is also an improvement as
      it is faster than the fully manual standard methods. The new methods developed in
      this study correlated (r2 > 0.85) with the standard method for samples of E. coli
      and for samples of generated airborne bioaerosols from household waste, although
      a correction factor is necessary. No correlation was found for samples of
      generated bioaerosols from composted waste. This work has established a
      possibility for improving exposure assessment of airborne microorganisms by means
      of image processing instead of manual counting.

PMID- 9155241
TI  - A comparative study of the clearance of respirable para-aramid, chrysotile and
      glass fibres from rat lungs.
AB  - A number of studies have indicated that the relative toxicity of different fibre
      types after inhalation is related to their durability within lung tissue. The aim
      of this study was to assess the relative biopersistence of respirable para-aramid
      fibrils, chrysotile asbestos and code 100/475 glass fibres in rat lungs. The
      biopersistence of all three test fibres was measured by quantifying the changes
      in retained lung burden through time following 10 days inhalation exposure to the
      same target concentration (700 fibres ml-1) for each fibre type. The lung burden
      analyses for all three fibre types show large reductions in number and volume of
      retained fibres during the 16 months following exposure. Most of this reduction
      in lung fibre burden occurred during the first 3 months following exposure but
      the pattern of clearance of different size classes varies with fibre type. The
      para-aramid data show rapid clearance of the longest fibrils during the first
      months following exposure, combined with an initial increase in the numbers of
      shorter fibrils. This is consistent with the disintegration of para-aramid
      fibrils into shorter fragments that subsequently are more readily cleared by
      macrophages. The code 100/475 glass fibre data also show rapid clearance of the
      longer fibres combined with an increase in the numbers of very short fibres,
      consistent with the removal of long fibres through disintegration. In contrast,
      the chrysotile data show a more rapid reduction in the numbers of retained short
      fibres than of long fibres, which is consistent with preferential clearance of
      short fibres by macrophages and minimal transverse breakage of fibres. The
      biopersistence of all three fibre types, in terms of overall percentage of fibres
      retained after 16 months is similar, but the durability of long (> 15 microns)
      chrysotile fibres is very much greater than that of long fibres of code 100/475
      glass or para-aramid. The clearance of the three fibre types cannot be adequately
      described by the first order kinetic model that is often applied in studies of
      lung clearance. The apparent half time of clearance of each of the fibre types
      depends on the size fraction and time interval examined.

PMID- 9155242
TI  - Monitoring and modelling of exposure to ethanol in hairdressing salons.
AB  - Personal exposure to solvents was studied among hairdressers in 28 salons in two
      regions during two seasons in The Netherlands. Ethanol was used as a marker for
      solvent exposure. Auxiliary data, such as salon and work characteristics,
      meteorological conditions and information on the presence of control measures,
      were collected during the measurements. The average exposure to ethanol was
      almost a factor of 200 below the occupational exposure limit, but differences in
      average ethanol concentrations up to a factor of 30 were present between salons.
      Exposure concentrations were significantly higher on Fridays than on other days
      of the week. Contrary to expectation, exposures were somewhat lower in the spring
      than in the summer and in an urban than a semi-rural area. An empirical
      statistical model based on exposure data collected during the first measurement
      period appeared not to be valid for the encountered circumstances in the second
      measurement period. An alternative classification scheme based on two easily
      obtainable salon and task characteristics was elaborated. This scheme will be
      applied in an ongoing epidemiological study on reproductive disorders among
      hairdressers and their offspring.

PMID- 9155243
TI  - 200 years of amphibian water economy: from Robert Townson to the present.
AB  - In the 1790s, Robert Townson established the main features of the water economy
      of terrestrial amphibians: rapid evaporative water loss in dry surroundings,
      'drinking' by absorption of water through the abdominal skin pressed against
      moist substrates, and use of the urinary bladder as a reservoir from which water
      is reabsorbed on land. This knowledge was of little interest to the establishment
      in the first half of the nineteenth century of experimental physiology as a basic
      medical discipline, when frogs became models in the elucidation of general
      physiological processes. Townson's pioneer contributions to amphibian physiology
      were forgotten for 200 years (Jorgensen 1994b). During (1901) and particularly
      Overton (1904) restored knowledge about amphibian water economy to the level
      reached by Townson, but the papers had little impact on the young science of
      animal physiology because they primarily aimed at elucidating the transport of
      fluids across membranes. Frog skin remained a model preparation in such studies
      throughout the century. With the establishment of terrestrial ecology early in
      the century, the relations of animals, including amphibians, to water became a
      central theme. Concurrently with comparative studies of amphibian water economy
      in an ecological setting, the subject proceeded as an aspect of animal
      osmoregulation. Adolph (1920-1930) and Rey (1937a) established the highly dynamic
      nature of water balance in amphibians in water and on land. Their observations
      indicated functional links between environment, skin and kidneys, the nature of
      which remained to be explored. Thorson & Svihla (1943) reopened the ecological
      approach in a comparative study of the relations between amphibian habitat and
      tolerance of dehydration. By mid-century, the central themes of amphibian
      adaptations to terrestrial modes of life were re-established, except for the
      function of the bladder as a water-depot. During the following decades, a rich
      literature appeared, particularly focusing on adaptations of amphibians to arid
      environments. Thus, in the 1970s, it was found that 'waterproofing' of the highly
      permeable skins by means of skin secretions had evolved independently in several
      families of tropical arboreal frogs, and that a number of amphibians that
      aestivate whilst burrowed in dry soil could reduce evaporation by forming cocoons
      from shed strata cornea. In 1950-1970 the role of bladder urine as a water depot
      in terrestrial amphibians was recognized: this did not change the established
      view of water balance in terrestrial amphibians as alternating between
      dehydration on land and rehydration in response to the deficit in body water.
      Amphibians may, however, maintain normal water balance whether the ambient medium
      is water or air by means of little understood integrated mechanisms in control of
      cutaneous drinking behaviour, water permeability of the skin and bladder wall,
      and urine production.

PMID- 9155244
TI  - Variation in mate choice and mating preferences: a review of causes and
      consequences.
AB  - The aim of this review is to consider variation in mating preferences among
      females. We define mating preferences as the sensory and behavioural properties
      that influence the propensity of individuals to mate with certain phenotypes. Two
      properties of mating preferences can be distinguished: (1) "preference functions'
      the order with which an individual ranks prospective mates and (2) "choosiness'
      the effort an individual is prepared to invest in mate assessment. Patterns of
      mate choices can be altered by changing the costs of choosiness without altering
      the preference function. We discuss why it is important to study variation in
      female mating behaviour and identify five main areas of interest: Variation in
      mating preferences and costs of choosiness could (1) influence the rate and
      direction of evolution by sexual selection, (2) provide information about the
      evolutionary history of female preferences, (3) help explain inter-specific
      differences in the evolution of secondary sexual characteristics, (4) provide
      information about the level of benefits gained from mate choice, (5) provide
      information about the underlying mechanisms of mate choice. Variation in mate
      choice could be due to variability in preference functions, degree of choosiness,
      or both, and may arise due to genetic differences, developmental trajectories or
      proximate environmental factors. We review the evidence for genetic variation
      from genetic studies of heritability and also from data on the repeatability of
      mate-choice decisions (which can provide information about the upper limits to
      heritability). There can be problems in interpreting patterns of mate choice in
      terms of variation in mating preferences and we illustrate two main points.
      First, some factors can lead to mate choice patterns that mimic heritable
      variation in preferences and secondly other factors may obscure heritable
      preferences. These factors are divided into three overlapping classes,
      environmental, social and the effect of the female phenotype. The environmental
      factors discussed include predation risk and the costs of sampling; the social
      factors discussed include the effect of male-male interactions as well as female
      competition. We review the literature which presents data on how females sample
      males and discuss the number of cues females use. We conclude that sexual
      selection studies have paid far less attention to variation among females than to
      variation among males, and that there is still much to learn about how females
      choose males and why different females make different choices. We suggest a
      number of possible lines for future research.

PMID- 9155245
TI  - Role of fetal and infant growth in programming metabolism in later life.
AB  - Fetal growth and development is dependent upon the nutritional, hormonal and
      metabolic environment provided by the mother. Any disturbance in this environment
      can modify early fetal development with possible long-term outcomes as
      demonstrated by extensive work on 'programming'. Growth restriction resulting
      from a deficit in tissue/organ cell number (as measured by tissue DNA content) is
      irrecoverable. However, when the cell size (or cell protein content) is reduced,
      the effects on growth may not be permanent. Recent epidemiological studies using
      archival records of anthropometric measurements related to early growth in humans
      have shown strong statistical associations between these indices of early
      development and diseases in later life. It has been hypothesised that the
      processes explaining these associations involve adaptive changes in fetal organ
      development in response to maternal and fetal malnutrition. These adaptations may
      permanently alter adult metabolism in a way which is beneficial to survival under
      continued conditions of malnutrition but detrimental when nutrition is abundant.
      This hypothesis is being tested in a rat model which involves studying the growth
      and metabolism in the offspring of rat dams fed a low-protein diet during
      pregnancy and/or lactation. Using this rat model, it has been demonstrated that
      there is: (i) Permanent growth retardation in offspring nursed by dams fed a low
      protein diet. (ii) Permanent and selective changes in organ growth. Essential
      organs like the brain and lungs are relatively protected from reduction in growth
      at the expense of visceral organs such as the liver, pancreas, muscle and spleen.
      (iii) Programming of liver metabolism as reflected by permanent changes in
      activities of key hepatic enzymes of glycolysis and gluconeogenesis (glucokinase
      and phosphoenolpyruvate carboxykinase) in a direction which would potentially
      bias the liver towards a 'starved' setting. We have speculated that these changes
      could be a result of altered periportal and perivenous regions of the liver which
      may also affect other aspects of hepatic function. (iv) Deterioration in glucose
      tolerance with age. (v) An increase in the life span of offspring exposed to
      maternal protein restriction only during the lactation period, and a decrease in
      life span when exposed to maternal protein restriction only during gestation.
      These studies show that hepatic metabolism and even longevity can be programmed
      by events during early life.

PMID- 9155246
TI  - Ambient particles and health: lines that divide.

PMID- 9155247
TI  - Evaluation of virtual source beam configurations for rapid tomographic
      reconstruction of gas and vapor concentrations in workplaces.
AB  - Beam path average data from an Open Path Fourier Transform Infrared (OP-FTIR)
      spectrometer can be used to reconstruct two-dimensional concentration maps of the
      gas and vapor contaminants in workplaces and the environment using computed
      tomographic (CT) techniques. However, a practical limitation arises because in
      the past, multiple-source and detector units were required to produce a
      sufficient number of intersecting beam paths in order to reconstruct
      concentration maps. Such a system can be applied to actual field monitoring
      situations only with great expense and difficulty. A single monostatic OP-FTIR
      system capable of rapid beam movement can eliminate this deficiency. Instead of
      many source and detector units, a virtual source arrangement has been proposed
      using a number of flat mirrors and retroreflectors to obtain intersecting folded
      beam paths. Three virtual source beam configurations generated for a single-beam
      steerable FTIR system were tested using 54 flat mirrors and four retroreflectors
      or 54 flat mirrors and 56 retroreflectors mounted along the perimeter walls of a
      typical 24- x 21-ft test room. The virtual source CT configurations were
      numerically evaluated using concentration maps created from tracer gas
      concentration distributions measured experimentally in a test chamber. Synthetic
      beam path integral data were calculated from the test maps and beam
      configurations. Computer simulations of different beam configurations were used
      to determine the effects of beam geometry. The effects of noise and peak reducing
      artifacts were evaluated. The performance of the tomographic reconstruction
      strategy was tested as a function of concentration and concentration gradients.

PMID- 9155248
TI  - Background air concentrations of Cr(VI) in Hudson County, New Jersey:
      implications for setting health-based standards for Cr(VI) in soil.
AB  - An accurate measure of "background" airborne Cr(VI) concentrations will be
      necessary to derive site-specific health-based Cr(VI) soil concentrations at
      sites containing chromite ore processing residues (COPR) in Hudson County, NJ. To
      date, no such data have been collected in New Jersey. This paper describes an air
      sampling program designed to measure background concentrations of Cr(VI) in
      Hudson County and compare those concentrations with the air sampling results
      obtained previously at 30 COPR sites in Hudson County. Background airborne Cr(VI)
      concentrations ranged from 0.2 to 3.8 ng/m3 with an arithmetic mean of 1.2 ng/m3.
      Comparisons of the airborne Cr(VI) concentrations previously measured at 30 COPR
      sites indicated that more than two-thirds of the sites had mean airborne Cr(VI)
      concentrations that were not statistically significantly greater than background.
      Our findings suggest that, in general, vehicle disturbance is required for
      significant soil suspension to occur at these sites. Since airborne Cr(VI)
      concentrations at many of these sites are close to background, it is critical
      that background airborne Cr(VI) levels be considered when deriving health-based
      soil standards at the COPR sites.

PMID- 9155249
TI  - An analysis of Michigan and California CO remote sensing measurements.
AB  - Remote sensing measurements of CO emissions from onroad vehicles were made in
      California in 1991 and in Michigan in 1992. It was determined that both fleets
      had a small linear increase in the high emitter frequency (vehicles emitting more
      than 4% CO) as a function of vehicle age for 1986 and newer model vehicles.
      Although high emitting vehicles were only a small minority of the fleet, they had
      a dominant impact on the mean CO and total CO emitted by the fleet. In Michigan,
      the highest emitting 5% of passenger cars generated 45% of the CO from cars. In
      California, the highest emitting 5% of passenger cars generated 38% of the CO
      from cars. There was a high correlation between the mean CO emitted by each model
      year of vehicle and the frequency of high emitting vehicles within the model year
      for both the Michigan and California fleets. The frequency of high emitters
      within any model year had no obvious relation to that model year's certification
      standards. The high emitter frequencies for vehicles less than nine years old
      were very similar for the California and Michigan fleets. An increase in the high
      emitter frequency in the ten-year-old and older Michigan passenger car fleet
      (relative to the California passenger car fleet), suggests, but does not
      conclusively demonstrate, that the rate of high emitters in Michigan and
      California is reduced by the inspection and maintenance (I/M) programs.

PMID- 9155250
TI  - Interlaboratory study of a test method measuring total volatile organic compound
      content of consumer products.
AB  - Consumer products are potentially significant sources of volatile organic
      compounds (VOCs), which are precursors to the formation of ozone in photochemical
      smog. To address the problem of ozone formation in ambient air, the U.S.
      Environmental Protection Agency (EPA) has been involved in the development of
      test methods for measuring the VOC content of consumer products. This paper
      describes results of an interlaboratory study to estimate the repeatability
      (precision of analyses performed by a single laboratory) and reproducibility
      (precision of analyses performed by different laboratories) of the consumer
      products' VOC measurement method based on EPA Method 24 (for VOCs in surface
      coatings). The mean method repeatability was 2.7 wt% VOC, and the mean method
      reproducibility was 4.8 wt% VOC. Method repeatability ranged from 0.2 to 4.4 wt%
      VOC, and reproducibility ranged from 0.6 to 11.9 weight percent VOC. The
      precision of the VOC method for consumer products is similar to the precision of
      EPA Method 24 for surface coatings.

PMID- 9155253
TI  - Mutants of Arabidopsis as tools to understand the regulation of phenylpropanoid
      pathway and UVB protection mechanisms.
AB  - Plants accumulate certain phenylpropanoid compounds in the vacuoles of their
      epidermal and subepidermal cell layers thereby protecting the underlying tissue
      against UVB-induced damage. However, a number of mutants of Arabidopsis thaliana
      are known that fail to synthesize these protective pigments, thereby allowing
      harmful UVB radiation to penetrate into their dermal layers. Study of several of
      these nonlethal mutants, defective in various aspects of flavonoid and lignin
      biosynthesis, has led to a better understanding of the coordinate regulation and
      expression of important genes as well as of mechanisms involved in plant defense
      against UVB radiation. The characteristics of the various phenylpropanoid mutants
      of Arabidopsis, viz. flavonoid mutants (banyuls [ban]; increased chalcone
      synthase expression 1 [icx1]; transparent testa [tt] and ultraviolet sensitive
      [uvs]) and hydroxycinnamic acid ester mutants (ferulic acid hydroxylase 1 [fah1]
      and sinapoylglucose accumulator 1 [sng1]) are discussed in detail. We have
      briefly touched upon, wherever relevant, the unique aspects in other plant
      species too.

PMID- 9155254
TI  - Excited state properties of the siderophore pyochelin and its complex with zinc
      ions.
AB  - The critical effects of pH on the electronic absorption and fluorescence
      characteristics of the siderophore, pyochelin, are investigated. A single anionic
      species is shown to be sufficient to explain the data obtained under alkaline
      conditions. In acidic solutions, several competing ground- and excited-state
      equilibria are present, which lead to fluorescence emissions from both the
      protonated form of pyochelin and its phenolate ion. From the spectroscopic data
      we are also able to show that pyochelin interacts with zinc ions in the ground
      state via its anionic form, thereby confirming that this siderophore does not
      bind Fe(III) ions uniquely.

PMID- 9155255
TI  - Photophysical properties of gilvocarcins V and M and their binding constant to
      calf thymus DNA.
AB  - Absorption and emission techniques were used to characterize the ground (S0),
      singlet (S1) and triplet states (T1) of gilvocarcin V (GV) and gilvocarcin M (GM)
      in different solvents. Aggregation of GV with dimerization constant equal to 7800
      M-1 is observed in 10% dimethyl-sulfoxide (DMSO)/water. The photophysical
      properties of the S1 state of these molecules are more sensitive to changes in
      solvent characteristics than the corresponding ground states. The absorption of
      visible light by GV and GM results in a higher dipole moment of the excited state
      causing a red shift in the fluorescence spectra with increasing solvent polarity.
      The fluorescence quantum yield remains practically unchanged with changes in
      solvent properties unless water is present as a co-solvent. Both phi f and tau f
      values corresponding to GV in DMSO are larger than those of GM, whereas in 10%
      DMSO/H2O the opposite is observed. Thus, GV is more susceptible to other
      deactivation pathways besides emission in the presence of water than GM. The
      relative phosphorescence quantum yield (phi p = 0.03) and the triplet energy (ET
      = 52 kcal/mol) of GV and GM are similar. The S0-S1 energy difference is 63
      kcal/mol for GV, whereas for GM it is 67. Thus, the singlet-triplet energy
      difference is 11 and 15 kcal/mol, respectively. The PM3/CI calculated electronic
      structures of these compounds are consistent with the observed photophysical
      properties. The dark binding constants of GV to calf thymus DNA ([1.1-0.08] x
      10(6) M-1) are about an order of magnitude larger than those of GM ([0.24-0.018]
      x 10(6) M-1) at different ionic strengths (0-2.00 M NaCl). Also, the number of
      gilvocarcin molecules bound per base pair is smaller for GM than for GV. These
      differences in dark DNA binding parameters between GV and GM could have
      implications in the large photocytotoxic ability of GV as compared to GM.

PMID- 9155256
TI  - UVB irradiation induces changes in cellular localization and phosphorylation of
      mouse HSP27.
AB  - We investigated the induction, cellular localization and phosphorylation of a low
      molecular weight stress protein (heat shock protein 27, HSP27) by UVB (290-320
      nm, max. 312 nm) irradiation stress using immunoblot and indirect
      immunofluorescence analysis in in vivo and in vitro experiments. The HSP27 was
      constitutively expressed and distributed in the cytoplasmic fraction of Pam 212
      cells (mouse keratinocyte line) or dorsal skin. The increase in the cytoplasm
      HSP27 level induced by UVB irradiation was less than two-fold that in
      nonirradiated controls. On the other hand, the translocation of HSP27 from
      cytoplasm to the nucleus or perinuclear area was time- and dose-dependently
      induced by UVB irradiation. After UVB irradiation, three isoforms having
      different isoelectric points were detected in nucleic HSP27 by two-dimensional
      immunoblotting. The most basic isoform was the unphosphorylated type and the two
      acidic isoforms were phosphorylated, suggesting that HSP27 is phosphorylated in
      response to UVB irradiation and accumulates in or around the nucleus as a
      phosphorylated isoform. These results suggest that the translocation and
      phosphorylation of HSP27 are induced in response to UVB-irradiation stress.

PMID- 9155258
TI  - Urocanic acid concentration and photoisomerization in Caucasian skin phototypes.
AB  - To investigate the relationship between erythemal sensitivity of the skin to UV
      radiation and epidermal urocanic acid (UCA) concentration, 45 healthy volunteers
      of anamnestic skin phototypes (ASP) 1-IV were studied. In 16 of the subjects, we
      analyzed UCA photoisomerization after graded UVB exposures. The median and mean
      total UCA concentration in unirradiated skin was 22.4 and 35.3 nmol/cm2, and no
      statistically significant difference in total UCA concentrations was detectable
      either between ASP I through II and III through IV or between the phototested
      skin type (PSP) groups 1 through 2 and 3 through 4. The relative amount of the
      cis-isomer varied between 3 and 35%, with median and mean values of 7 and 12%,
      respectively. No statistically significant difference in absolute or relative cis
      UCA concentrations was detectable between ASP I through II and III through IV,
      but a significantly lower absolute (P < 0.009) and relative (P < 0.002) cis-UCA
      concentration in unirradiated skin was recorded in PSP groups 1 through 2,
      compared to types 3 through 4. In all tested subjects, an erythemally weighted
      dose of 1 mJ/cm2 sufficed to cause trans- to cis-UCA isomerization. When
      comparing photosensitive (skin phototype I) and phototolerant (phototypes III and
      IV) individuals, who were irradiated with a reference 5 mJ/cm2 UV dose or with
      fractions of 0.1-1.0 of their individual minimal erythema dose values, no skin
      phototype-dependent difference in ability to photoisomerize was discernible.

PMID- 9155257
TI  - The photodynamic effect of Victoria blue BO on peripheral blood mononuclear and
      leukemic cells.
AB  - The photodynamic effect of Victoria blue BO (VB-BO) and photoirradiation on
      peripheral blood mononuclear cells was studied. The cells were preincubated with
      VB-BO followed by photoirradiation and overnight culture. The highest percentage
      of dead cells (propidium iodide assay in flow cytometry) was seen in the monocyte
      population. The lymphocytes showed a lower sensitivity to VB-BO photodynamic
      action than the monocytes (12% vs 80% of PI-positive cells). The effect of VB-BO
      and phototreatment on lymphocyte function was studied using a mitogen-induced
      proliferation assay. A decrease of mitogen response was observed. The VB-BO and
      photoirradiation were also used on leukemic cells. The leukemic cells from acute
      myeloid leukemia and B precursors leukemia were sensitive to VB-BO photodynamic
      action. The high VB-BO sensitivity of monocytes and leukemic cells (myeloid and
      lymphoid B derived) suggests possible application of VB-BO for selective
      depletion of monocytes or sensitive leukemic cells.

PMID- 9155259
TI  - The effect of chronic treatment of mice with urocanic acid isomers.
AB  - Trans-urocanic acid (trans-UCA) accumulates in the upper layers of the epidermis
      and can be isomerized to cis-UCA by UV light irradiation. Cis-urocanic acid
      possesses immunosuppressive properties that have led to its consideration as one
      of the initiators of UV-induced immunosuppression. High quantities of cis-UCA
      persist in human skin for prolonged periods in the summer months. In the present
      study, mice were injected intradermally with trans-UCA and cis-UCA three times a
      week for 4 weeks in order to ascertain the long-term effects of the presence of
      these compounds in the skin. The weight of mice and of their spleens were
      unaffected by the cis- or trans-UCA treatment. A decrease in thymus weight,
      accompanied by an increase in lymph node weight, was detected in the cis-UCA
      treated mice compared with trans-UCA-treated mice and untreated controls. A net
      accumulation of lymphocytes and dendritic cells (DC) in lymph nodes was evident
      following cis-UCA treatment but the percentage of both CD4+ and CD8+ lymphocytes
      as well as Ia+ DC remained constant among the different treatment groups,
      indicating that there was no specific migration or proliferation of a particular
      subset of cells. The in vitro lymphoproliferative response of lymph node cells to
      the mitogen concanavalin A was significantly sup pressed by cis-UCA treatment.
      The density of Langerhans cells in the epidermis of the ears was not altered by
      the chronic cis-UCA treatment. However, chronic cis-UCA treatment did suppress
      the mixed skin lymphocyte reaction response utilizing epidermal cells from the
      ears (an uninjected area of skin), indicating a systemic suppression. Compared
      with trans-UCA treatment, chronic cis-UCA treatment did not cause a significant
      reduction in the contact hypersensitivity response to oxazolone or the delayed
      hypersensitivity response to herpes simplex virus. Thus, chronic treatment with
      cis-UCA led to the suppression of some, but not all, of the immune parameters
      that are affected by UVB irradiation.

PMID- 9155260
TI  - Factors affecting M13 bacteriophage inactivation by methylene blue
      photosensitization.
AB  - We have investigated the factors that affect the virucidal activity of methylene
      blue (MB) photosensitization. The M13 bacteriophage was more rapidly inactivated
      at higher temperatures (6 degrees C < 24 degrees C < 38 degrees C). Rate
      constants for inactivation were 0.072, 0.139 and 0.260 (log10 inactivation)/
      (J/cm2) at 6 degrees C, 24 degrees C and 38 degrees C, respectively. On the other
      hand, dye penetration into virus particles, which was monitored by the
      fluorescence of YOYO-1, was unchanged with incubation temperature. These data
      suggest that temperature dependency of M13 inactivation was due to factors other
      than dye permeability. The pH of the virus suspension also affected the rate of
      M13 inactivation by MB. The M13 bacteriophage was inactivated faster in basic
      suspensions and slower in acidic suspensions compared with neutral buffers. These
      results suggest that temperature and pH are factors that influence the extent of
      MB photosensitization, and hence, the control of these factors will be necessary
      for MB phototreatment of plasma products in transfusion medicine.

PMID- 9155261
TI  - Delivery of benzoporphyrin derivative, a photosensitizer, into atherosclerotic
      plaque of Watanabe heritable hyperlipidemic rabbits and balloon-injured New
      Zealand rabbits.
AB  - In this study we compared the plasma distribution and arterial accumulation of a
      photosensitizer, benzoporphyrin derivative (BPD), in two models of
      atherosclerosis: the spontaneous lesions of the Watanabe heritable hyperlipidemic
      (WHHL) rabbit and induced lesions of the balloon-injured, cholesterol-fed New
      Zealand white (NZW) rabbit. Selective uptake and retention of a photosensitizer
      by the abnormal portion of a vessel is a necessity in order for photodynamic
      therapy to become a successful modality for inhibition of intimal hyperplasia,
      selective removal of atherosclerotic tissue or imaging of diseased arteries.
      Liposome-based formulations were compared to freshly isolated native low density
      lipoprotein (LDL) and acetylated-LDL (Ac-LDL) as delivery vehicles for BPD.
      Plasma distribution of the photosensitizer was analyzed by KBr density gradient
      ultracentrifugation. Although the delivery vehicle influenced plasma distribution
      immediately postinjection, BPD subsequently partitioned according to the plasma
      concentration of the lipoproteins. Photosensitizer level in plaque and normal
      artery specimens was determined by ethyl acetate extraction and
      spectrofluorometric measurement. The measurement of BPD in normal and
      atherosclerotic arterial tissue demonstrated a selective accumulation in
      atherosclerotic tissue. Preassociation with LDL and Ac-LDL enhanced accumulation
      of BPD in atherosclerotic tissue when compared with normal artery (mean ratios of
      2.8 and 4.1 were achieved, respectively). These results indicate that the
      preferential uptake of BPD by atherosclerotic plaque can be enhanced by
      preassociation with plasma lipoproteins, suggesting that light activation could
      lead to a highly selective destruction of diseased vascular tissue.

PMID- 9155262
TI  - Singlet oxygen-mediated inactivation of acetylcholinesterase: a comparison of
      purified enzyme in solution and enzyme bound to K562 leukemia cells.
AB  - We have compared the singlet oxygen-mediated inactivation of acetylcholinesterase
      (ACE) in solution with the inactivation of ACE on the surface of K562 leukemia
      cells. In solution, the actions of the singlet-oxygen quenchers, methionine,
      azide, disodium [N,N'-ethylenebis (5-sulfosalicylideneimminato)]nickelate(II) (Ni
      chelate 1) and disodium [(N,N'-2,3-propionic acid)bis(5-sulfosal
      icylideneimminato)] nickelate(II) (Ni-chelate 2) could be explained
      quantitatively by assuming their only mechanism of action was to quench singlet
      oxygen. The singlet oxygen quenchers, azide, Ni-chelate 1 and Ni-chelate 2,
      caused smaller inhibitions in the rate of singlet oxygen-mediated inactivation of
      ACE on K562 cells than ACE in solution. The effects of these quenchers and of
      deuterium oxide were interpreted using a mathematical model of singlet-oxygen
      quenching and diffusion to estimate the lifetime of singlet oxygen near the cell
      surface. The azide quenching data and the deuterium-oxide data gave lifetimes of
      0.9 +/- 0.2 microsecond and 0.45 +/- 0.15 microsecond, respectively. The
      increases in ACE inactivation lifetime caused by the nickel chelates were
      anomalously large. The unexpectedly large quenching due to the nickel chelates
      may have been due to a nonuniform distribution of the chelates in the cytoplasm
      with a large concentration of the chelate near the cell membrane.

PMID- 9155263
TI  - Phthalocyanine photodynamic therapy: disparate effects of pharmacologic
      inhibitors on cutaneous photosensitivity and on tumor regression.
AB  - The phthalocyanines are promising second-generation photosensitizers that are
      being evaluated for the photodynamic therapy (PDT) of malignant tumors. In vivo
      studies with the silicon phthalocyanine Pc 4 have shown that it is highly
      effective at causing regression of RIF-1 tumors in C3H/HeN mice in PDT protocols.
      Because cutaneous photosensitivity is the major complication of photosensitizers
      used for PDT, experiments were performed to evaluate the effect of inhibitors of
      the inflammatory response (cyproheptadine, dexamethasone, pentoxifylline, and
      tumor necrosis factor alpha [TNF-alpha] antibodies) on Pc 4-induced cutaneous
      photosensitivity and tumor regression. The C3H/HeN mice were injected with either
      Pc 4 or Photofrin and were exposed to 86 J/cm2 of filtered radiation emitted from
      a solar simulator. Animals were irradiated at 1, 3, 7, 10, 14 and 28 days
      postinjection. Cutaneous photosensitivity was assessed using the murine ear
      swelling response. Cyproheptadine, dexamethasone, pentoxifylline and TNF-alpha
      antibodies were administered prior to illumination to assess their ability to
      block Pc 4-induced cutaneous photosensitivity and to evaluate whether such
      treatment adversely influenced Pc 4 PDT-induced tumor regression. Compared to
      Photofrin, Pc 4 produced cutaneous photosensitivity that was transient, resolving
      within 24 h, and that could be elicited for only 10 days after administration. In
      contrast, Photofrin caused photosensitivity that required 4 days to resolve and
      could be elicited for at least 1 month after it was administered. The Pc 4
      induced cutaneous photosensitivity could be blocked by corticosteroids and an
      inhibitor of vasoactive amines (cyproheptadine). The TNF-alpha gene transcription
      was found to increase in keratinocytes following treatment with Pc 4 and light.
      The anti-TNF-alpha antibodies and pentoxifylline, an inhibitor of cytokine
      transcription, also prevented cutaneous photosensitivity, implicating TNF-alpha
      in the pathogenesis of Pc 4-induced cutaneous photosensitivity. None of these
      agents had any effect on Pc 4 PDT-induced tumor regression. Cyproheptadine,
      dexamethasone, pentoxifylline and TNF-alpha antibodies may be valuable
      pharmacologic agents in the management of cutaneous photosensitivity associated
      with PDT without altering the efficacy of this new therapeutic modality. The
      findings suggest that it should be possible to devise PDT protocols that block
      cutaneous photosensitivity without impairing the anti-tumor response to the
      agents.

PMID- 9155264
TI  - The photodynamic action of methylene blue on the ion channels of Paramecium
      causes cell damage.
AB  - The photodynamic effects of methylene blue (MB) on wild-type and mutant strains
      of Paramecium Were studied. From measurements of survival and cell motility under
      the continuous application of light in the presence of MB, the mutant strains
      remained alive for about three times longer than the wild-type strain. Although
      the resting potential of the mutant cells was similar to that of wild-type cells,
      the continuous photodynamic action shifted the membrane potentials of the mutant
      and wild-type cells to a depolarized level and a hyperpolarized level,
      respectively, from that before light application. Under voltage clamping, the
      mutant cells reduced not only the outward current elicited by the photodynamic
      action but also the outward tail current elicited by the preceding pulse of
      hyperpolarization. We conclude that the mutant strain is defective in the
      activation of Ca(2+)-dependent K+ channels. This defect might cause a reduction
      in the Ca2+ influx because of the suppression of the membrane hyperpolarization,
      which results in the elongation of survival time under the photodynamic action.

PMID- 9155265
TI  - Gene expression in skin tumors induced in hairless mice by chronic exposure to
      ultraviolet B irradiation.
AB  - We investigated the expressions of c-Ha-ras, c-jun, c-fos, c-myc genes and p53
      protein in the development of skin tumors induced by chronic exposure to UVB
      without a photosensitizer using hairless mice. When mice were exposed to UVB at a
      dose of 2 kJ/m2 three times a week, increased c-Ha-ras and c-myc transcripts were
      detected after only 5 weeks of exposure, while no tumor appeared on the exposed
      skin. The increase in gene expression continued until 25 weeks, when tumors,
      identified pathologically as mainly squamous cell carcinomas (SCC), developed in
      the dorsal skin. In these SCC, overexpression of c-fos mRNA was also observed
      along with the increases in c-Ha-ras and c-myc. A single dose of UVB (2 kJ/m2)
      applied to the backs of hairless mice transiently induced overexpression of the
      early event genes c-fos, c-jun and c-myc, but not c-Ha-ras, in the exposed area
      of skin. Accumulation of p53 protein was determined by Western blotting analysis
      or immunohistochemistry using monoclonal antibodies PAb 240 or 246, which
      recognize mutant or wild type, respectively. In the SCC, a mutant p53 protein
      accumulated in the cytoplasm and nucleus. After single-dose irradiation, the
      increased wild-type p53 protein was observed in the nuclei of epidermal cells.
      The present results suggest that overexpression of the c-fos, c-myc and c-Ha-ras
      genes, and the mutational changes in p53 protein might be associated with skin
      photocarcinogenesis. Moreover, overexpression of the c-Ha-ras and c-myc genes
      might be an early event in the development of UVB-induced skin tumors in mice.

PMID- 9155266
TI  - Form follows function. Occupational health nursing as a member of the management
      team.
AB  - Role, often designated by a given title, e.g., manager, has been one of the most
      common means of defining occupational health nursing practice. A function based
      model provides an opportunity to reframe the occupational health nurse as a
      member of the management team. This descriptive study characterized the functions
      of a random sample (40%) of members of the American Association of Occupational
      Health Nurses from eight Midwestern states (463) in 1994. With a 78% response
      rate, the most frequently performed function for all respondents was "evaluate
      status of employees returning to work after absence" (68%). The relative
      frequencies for functions performed by the associates degree nurses were very
      similar to those for diploma nurses (r = .889 based on a perfect relationship
      value of 1). Subjects with baccalaureates in nursing performed more educational
      programming than subjects with non-nursing baccalaureates who performed more
      frequently in a policy area. Type of masters preparation represented different
      functional activities. The department to which the respondent reported affected
      functions. Reviewing function by salary level revealed a linear relationship with
      certain functions by frequency. To facilitate the investigation of the role
      construct based on functions, the researchers conducted a principle components
      analysis of the data. Four principle components were found representing groups of
      functions that tended to be performed by the same sets of respondents. The
      functions in each component tended to cluster around common skills as defined by
      Hersey (1988).

PMID- 9155267
TI  - Ionizing radiation. An overview for the occupational health nurse. Agency for
      Toxic Substances and Disease Registry.
AB  - 1. Everyone is exposed to ionizing radiation. Approximately 82% of this exposure
      is natural background from cosmic and terrestrial sources, and 18% is due to man
      made sources. 2. Public exposure to ionizing radiation or contamination of the
      environment by radioactivity engenders intense fear. The emotional and
      psychologic stresses resulting from exposure should be recognized and addressed
      early in a radiation incident. 3. Health care providers should understand the
      physics, chemistry, and biology of radiation to communicate effectively about it.

PMID- 9155268
TI  - Occupational health surveillance. We're making progress, but is it enough?
AB  - 1. Surveillance data are used in the development of health strategies and
      policies. 2. The Sensor program bridges the gap that exists between the reporting
      of occupational disorders and infectious disease. 3. A shortage of health care
      professionals experienced in health surveillance has been a hindrance to the
      occupational health profession over the years. However, this is changing as more
      individuals seek advanced degrees. 4. As the ability to collect and analyze data
      improves, the health and safety of employees also should improve.

PMID- 9155270
TI  - Research and the Internet.

PMID- 9155269
TI  - Orthopedic problems of the upper extremities. Assessment and diagnosis.
AB  - 1. Cumulative trauma or repetitive motion disorders are among the most commonly
      reported occupational illness, and mainly affect the neck and upper extremities.
      2. The etiology of cumulative trauma disorders includes nerve compression
      secondary to inflammation and tendinitis secondary to microtearing at tendon
      insertions and/or friction irritation of the tendons. 3. Work postures, such as
      forward flexed position of head, neck, and shoulders; static loading of muscles;
      as well as repetitive motions can cause cumulative trauma disorders or aggravate
      pre-existing problems. 4. The occupational health nurse is in a unique position
      to encourage early reporting of these problems so that conservative treatment can
      be initiated, identify ergonomic issues at the worksite and institute change, and
      work closely with the orthopedist to manage clients effectively with clear
      communication and collaboration.

PMID- 9155271
TI  - Alternative treatments and occupational health nurse liability.

PMID- 9155272
TI  - Is a Labour government a better option for nurses?

PMID- 9155273
TI  - Are nurse practitioners a viable option?

PMID- 9155274
TI  - Treatments and healing rates in a community leg ulcer clinic.
AB  - Leg ulcer management is increasingly becoming a nurse-led specialty with
      practitioners implementing evidence-based care that is efficient, effective and
      resourceful. A large percentage of patients with leg ulceration are treated in
      the community. This article will discuss the healing rates and management of
      venous leg ulcers, many of which were longstanding problems, in a community leg
      ulcer clinic.

PMID- 9155275
TI  - A review of intrathecal baclofen in the management of spasticity.
AB  - Spasticity is associated with damage to the corticospinal tract and is a common
      complication of neurological disease. Patients with spasticity complain of
      stiffness, involuntary spasm and pain. The majority of patients are managed
      conservatively with physiotherapy and/or oral medication. However, 25-35% of
      patients will develop unacceptable side-effects or fail to respond to oral doses
      of antispasmodics. Surgical procedures such as myelotomy, rhizotomy and neurotomy
      have not been universally successful. More recently, intrathecal baclofen has
      become established as an important adjunct in the management of spasticity. This
      article describes the mechanism of action of baclofen, the delivery systems
      available and the criteria for patient selection. The screening phase, surgical
      procedure and specific postoperative observations are also described.

PMID- 9155276
TI  - Framework for a clinical career structure in nursing.
AB  - There is an urgent need to define and clarify a clinical career structure in
      nursing. The development of a career structure is hindered by the proliferation
      of titles currently used by nurses when developing their knowledge and skills. It
      is proposed that the term nurse practitioner be replaced by either generalist or
      specialist nursing practitioner, depending on the individual's bias, and that
      nurses with a bias towards medicine be designated paramedical nurse
      practitioners. A three-band clinical career structure is suggested, based on
      these categories. This structure would allow nurses to develop their knowledge
      and competency while either remaining in a broader, generalist area or
      specializing in a particular field. This structure includes an advanced nursing
      practitioner level to accommodate those nurses with extensive experience of
      clinical nursing situations. It is imperative that the nursing profession decides
      its career pathways, otherwise they may find others doing it for them.

PMID- 9155277
TI  - Development of specialist and advanced practice in North America.
AB  - North American literature provides interesting ideas about the nature of
      specialist and advanced practice which are useful in informing British thinking
      on these subjects. However, the two roles do not have the same meanings as their
      British counterparts. Clarification of the terminology used and the roles
      described are essential if we are to understand the concepts. This article
      presents an overview of the literature about clinical nurse specialist and
      advanced practitioner roles within North America and identifies differences and
      similarities between the two.

PMID- 9155278
TI  - Non-verbal communication: the importance of listening.
AB  - This article presents the author's personal reflection on how her nursing
      practice was enhanced as a result of losing her voice. Surprisingly, being unable
      to speak appeared to improve the nurse/patient relationship. Patients responded
      positively to a quiet approach and silent communication. Indeed, the skilled use
      of non-verbal communication through silence, facial expression, touch and closer
      physical proximity appeared to facilitate active listening, and helped to develop
      empathy, intuition and presence between the nurse and patient. Quietly 'being
      with' patients and communicating non-verbally was an effective form of
      communication. It is suggested that effective communication is dependent on the
      nurse's ability to listen and utilize non-verbal communication skills. In
      addition, it is clear that reflection on practical experience can be an important
      method of uncovering and exploring tacit knowledge in nursing.

PMID- 9155279
TI  - Residential alcohol detoxification: new role for mental health nurses.
AB  - This article discusses the philosophy and practice of a community-based
      residential detoxification service for people with alcohol problems. The service
      is provided on a direct-access basis and has a team of 19 nurses who are
      supported by a GP practice. The article highlights issues relevant to nursing in
      this community facility by referring to three case studies. The case studies
      demonstrate that this client group finds it difficult to access other forms of
      health and social care. The case examples emphasize both the qualitative aspects
      of nursing care and the decision-making involved in this type of service. The
      authors suggest that large populations with complex needs can be served by
      nursing-led services adopting a 'direct access' approach.

PMID- 9155280
TI  - Management of leisure time by prospective nurses.
AB  - A focus on the importance of leisure in the development of student nurses has
      been neglected in the 1990s. This study considers 444 prospective nurses on
      conventional, diploma and degree courses in two areas of England. It examines
      their activities associated with socializing, their social support networks and
      their use of clubs, sports and hobbies before entering nursing. It is evident
      that students enter nurse training with a wide variety of leisure experiences.
      Changing recruitment patterns and the structure of nurse training has an effect
      on the leisure needs of prospective nurses which must be addressed.

PMID- 9155281
TI  - Evidence-based nursing: where is the evidence?

PMID- 9155282
TI  - Clearer guidelines for PVS diagnosis required.

PMID- 9155284
TI  - A multicentre comparative evaluation of catheter valves.
AB  - Catheter valves are an alternative to leg bags for urine drainage, but no studies
      have yet been published which have compared the performance of different valves.
      This study was undertaken to evaluate the performance of the seven catheter
      valves available on the UK market in April 1996. The study was carried out by the
      Continence Products Evaluation (CPE) Network funded by the Medical Devices Agency
      (Department of Health). Each valve type was tested for 1 week by 19-36
      cognitively unimpaired and manually dextrous subjects recruited from 11 test
      centres. At the end of each week, subjects completed an evaluation form (based on
      a three-point rating scale) to record product performance. The same catheter
      valves were also tested for ease of opening/closing by 33 subjects (mostly
      catheter users) who had some manual impairment. Performance scores varied widely
      between products. It was found that, to be successful, a valve needs to be easy
      to manipulate, leak-free, comfortable and inconspicuous. Prescribers need to be
      aware of the strengths and limitations of different valves for appropriate
      product selection.

PMID- 9155283
TI  - The tragedy of healthcare rationing by age.

PMID- 9155285
TI  - A self-medication scheme in a post-coronary care unit.
AB  - The drug knowledge of 107 patients was determined before and after entering a
      self-medication scheme on the post-coronary care unit (PCCU) at City Hospital,
      Birmingham, and approximately 6 weeks post-discharge when these patients attended
      their cardiac rehabilitation classes. Fifty-two completed questionnaires were
      returned. The results indicated a general increase in patients knowledge about
      the names and side-effects of their drugs, the times at which they take them and
      the reasons for taking them, following self-medication. A smaller number of
      questionnaires (19) were completed 6 weeks after discharge. The responses to
      these suggested that patients who self-medicated in hospital showed greater drug
      knowledge, especially with regard to potential side-effects, than those who had
      not. Patients' confidence in their ability to self-medicate safely at home showed
      no relation to their actual knowledge. It is suggested that self-medication on
      the PCCU is an important part of the cardiac rehabilitation programme.

PMID- 9155286
TI  - Psychological preparation for nasogastric feeding in children.
AB  - Psychological preparation of children undergoing enteral nutrition by nasogastric
      tube was evaluated in a prospective study of 48 children nursed at home. They
      were randomly allocated to receive either standard informal preparation or
      detailed psychological preparation and support. The children were divided into
      two groups according to age: group A comprised toddlers and younger children aged
      2-6 years and group B comprised older children and adolescents aged 7-16 years.
      Detailed questionnaires were administered to all parents and older children by
      dietetic colleagues who were blinded to the type of preparation received by the
      children. The results emphasize that detailed psychological preparation of
      families takes time. Passage of a nasogastric tube was seen as very distressing
      to both parents and children. Having a nasogastric tube was perceived as a major
      problem by group A. There was no statistical difference in the effects of enteral
      nutrition between younger children who received routine preparation and those who
      received detailed preparation; however, parental assessment of their child's
      behaviour was the sole means of determining how the younger child felt and
      reacted. In group B, there were marked differences: scores suggested that those
      who received detailed preparation had been better prepared for enteral feeding in
      hospital and at home and that the passage of the nasogastric tube, although
      unpleasant, was less distressing to them (P < 0.05). Talking to a nurse and play
      therapist was seen by parents as essential (P < 0.05). The authors conclude that
      children should be prepared for painful procedures and followed up sensitively,
      according to their needs.

PMID- 9155287
TI  - The health of children looked after by local authorities.
AB  - There are some 40,000 children 'in care' in England and Wales, i.e. being 'looked
      after' by local authorities and living in foster and residential homes. These
      children come from highly disadvantaged social backgrounds and are likely to
      experience more serious health problems than the wider population. Despite this,
      there is evidence to suggest that their health needs are frequently neglected.
      This is reflected in the dearth of research information. Health professionals
      play a key role in combating child abuse and are particularly concerned about
      future mental health, self-injury and high levels of pregnancy in this group of
      children. Health promotion is therefore vital, but is complicated by the fact
      that this group of children often do not attend school. The Department of Health
      has introduced a major initiative which has a strong health dimension to help
      promote better care planning and monitoring for children who have been separated
      from their parents.

PMID- 9155288
TI  - Scholl compression hosiery in the management of venous disorders.
AB  - Graduated compression hosiery has an important role in the management of venous
      leg ulcers by counteracting chronic venous hypertension. The historically high
      rates of venous ulcer recurrence can be significantly reduced by optimizing
      compliance with the wearing of support hosiery. This is facilitated by providing
      information, practical support and opportunities for regular professional
      monitoring. Compliance is also aided by ensuring that the garment fits correctly
      and is comfortable and by offering the client a choice of products from those
      available.

PMID- 9155289
TI  - Wound care in the accident and emergency department.
AB  - Wound assessment in the accident and emergency (A&E) department has a different
      focus from that in other clinical areas because of the lack of available clinical
      information about the patient. A wound may have had a greater-physical impact
      than is immediately apparent and therefore a comprehensive skin assessment is
      often necessary. The wound will require thorough exploration and debridement to
      enable healing to take place with minimal complications. The methods of
      debridement and cleansing used in the A&E department are often unique because of
      the complexity of wound contamination. The variety of wounds encountered in this
      setting necessitate a large repertoire of dressing regimens. Modern wound
      management products can be adapted to meet the needs of the wounded patient in
      the A&E department.

PMID- 9155290
TI  - Extending the role of nurses as apolitical advocates.
AB  - During periods of ill health people may become disenfranchised. This article
      offers guidance on issues relating to voting rights. Both nurses' and clients'
      potential for participation can be enhanced by an understanding of the mechanisms
      set out in the Representation of the People Act (RPA) 1983 and the European
      Parliamentary Elections Act 1978. Through apolitical advocacy, nurses can assist
      patients in claiming their right to vote, since RPA 1983 applications by citizens
      require the nurse, midwife or health visitor to attest the client's claim of
      temporary or permanent incapacity which prevents their poll attendance on
      election day. Electoral registration officers are proactive in the formulation of
      registers with the aim of maximizing the numbers of eligible voters. However,
      they are not in a position to identify the health problems of particular
      individuals.

PMID- 9155291
TI  - Medical investigations. 1: Lumbar puncture.

PMID- 9155292
TI  - There is no such thing as a menial task in nursing.

PMID- 9155293
TI  - Doctors seek to transfer repetitive roles to nurses.

PMID- 9155294
TI  - Healthcare assistants need to be regulated.

PMID- 9155295
TI  - Clinical implications of circadian rhythmicity for nurses and patients.
AB  - Recent research suggests that our biological rhythms are regulated by the
      light/dark cycles and regular time cues in our environment which synchronize our
      internal body clocks to a 24-hour cycle. Altering these external cues can cause
      an imbalance, in psychophysiological variables which adversely affect an
      individual's performance and health. This article considers the implications of
      desynchronized circadian rhythms on nurses working shifts in a continually
      changing temporal environment. It then discusses the impact this has on patients,
      their illness and their care. The authors suggest ways in which an understanding
      of the principles of circadian rhythms can be used to reduce the negative effects
      of hospitalization on patients, possibly even aiding their recovery.

PMID- 9155296
TI  - Testicular cancer: the importance of effective health education.
AB  - Testicular cancer is the commonest malignancy in the UK among men aged 20-34
      years. Although rare, it is one of the most curable cancers. There is a
      correlation between the incidence of testicular cancer and age, histology, social
      class and geographical region. As survival is dependent on early detection, men
      should be encouraged to practise testicular self-examination at least every 6
      months. Nurses are in an ideal position to teach and encourage such practice.
      However, for optimal effect, health education programmes need to take into
      account complexities, such as cultural diversity, if patients are to heed vital
      and in some cases life-sustaining advice.

PMID- 9155297
TI  - Pressure sores: incidence, risk assessment and prevention.
AB  - Pressure sores have a physiological basis which, in common with other disease
      processes, is influenced by intrinsic and extrinsic factors unique to the
      individual. A comprehensive patient assessment will identify factors affecting
      the individual and consequently direct preventive intervention. The issue of
      pressure sores should be addressed at a patient, trust or regional level to
      ensure that preventive strategies/policies cross all healthcare boundaries.
      Identification of the size of the problem is the starting point upon which a
      preventive strategy can be built. A comprehensive strategy for pressure sore
      prevention has existed in the USA since 1992, and its contents demonstrate the
      multidisciplinary input required to develop and implement the recommendations.
      Nurses have a key role in the prevention of pressure sores; however, they need
      educational, managerial and financial support in order to function effectively
      within this role.

PMID- 9155298
TI  - Pressure-relieving equipment: criteria and selection.
AB  - The selection of equipment for pressure sore prevention and management is
      extremely complex, with many variables to consider. There is a considerable lack
      of data to support the use of individual pieces of equipment, and so additional
      criteria need to be considered. A logical approach, taking into account the
      objectives of treatment, the modality of action, and the resources available,
      enables an optimal choice to be reached which should satisfy both the patient and
      the staff involved.

PMID- 9155299
TI  - Pressure sores: adopting the principles of risk management.
AB  - This article examines the continuing problem of pressure sores in the NHS from a
      purchasing and a providing manager's perspective. Risk management and the need
      for clinical effectiveness in treatment and prevention strategies are discussed.
      Reporting systems are advocated as a means to estimate risk and to form a store
      of information that will enable a response to made when problem areas are
      identified. Nursing advice and input into the contracting process is vital. The
      need for purchasers and NHS managers to work together to ensure that effective
      interventions are implemented to reduce both the financial burden on the NHS and
      the physiological insult offered to patients is stressed.

PMID- 9155300
TI  - Prison nursing: the tension between custody and care.
AB  - All prisons provide healthcare services which aim to meet the needs of prisoners.
      The goal of the service is to give prisoners access to the same quality and range
      of health care as the NHS gives the general public. However, within the prison
      environment priorities centre around order, control and discipline and therefore
      an ethos of health care needs to be developed. Custody reduces the prisoner's
      opportunity for self-care and independent action as inmates have to consult
      nursing or medical staff for even the most simple remedies. Nursing staff in the
      prison service can play a significant part in primary health care, mental
      disorder and health promotion. Nurses have the knowledge, skills and attitudes
      needed to deal with this diverse and vulnerable prison population and to promote
      a positive interface between custody and care.

PMID- 9155301
TI  - Consumerism: do patients have power in health care?
AB  - In market rhetoric NHS patients are considered to be consumers of health care.
      This article considers what attributes and rights consumers have and analyses the
      possible forces limiting and/or driving their accedence into present day health
      care. While the term patient is associated with passivity, the term consumer
      conjure up notions of rights, power and empowerment. Consumer power may take two
      forms: the ability to make choices and legal rights. Yet within the NHS there are
      many forces that attempt to oppose and restrain consumer power.

PMID- 9155302
TI  - Community participation within an Irish Health Board area.
AB  - This article gives a brief analysis of the concept of community participation
      followed by an account of a small study exploring the views and practices of two
      populations. Public health nurses have implemented their 'community as client'
      role and under favourable conditions would wish to develop further this aspect of
      their work. Women in the community are aware of the primary healthcare services
      available to them and as demonstrated by their comments have a holistic
      understanding of health. The study shows that both public health nurses and women
      in the community are interested and willing to take part in actions to improve
      health and welfare. Before genuine community partnership is developed a more
      defined leadership role which incorporates the skills of both community
      empowerment and community organization is needed.

PMID- 9155303
TI  - Nurses with HIV/AIDS must not be stigmatized.

PMID- 9155304
TI  - Anesthesia for trauma during wartime.
AB  - Trauma during wartime has been the scourge of the ages. Conventional anesthesia
      with ether has been available since 1846 when it was demonstrated in Boston by a
      dentist named William Morton. Subsequently, ether was used during the Mexican
      American War in 1847, and chloroform was used during the Crimean War from 1854 to
      1856. Nurse anesthetists have made substantial contributions to care of the war
      injured by initiating acute airway management and resuscitation efforts and by
      the administration of anesthesia care for critically injured war casualties
      undergoing surgical procedures. They have further contributed to goodwill in war
      torn areas by providing anesthesia care to many civilian children and adults
      living in these areas of conflict. The evolution of nurse anesthesia
      contributions to the treatment of traumatized war casualties is the central focus
      of this article.

PMID- 9155305
TI  - Trauma in the rural setting.
AB  - This article provides an overview of rural trauma, focusing on the challenges
      that exist for rural providers compared with those who work in urban trauma
      centers. The authors outline the role of a Certified Registered Nurse Anesthetist
      working in trauma care at rural hospitals and address responsibilities involved
      in this expanded role.

PMID- 9155306
TI  - Trauma to the neck and larynx.
AB  - Trauma is the leading cause of death for persons from 8 months to 44 years of
      age. The precise incidence of neck trauma is unknown. Autopsy studies have shown
      that the majority of the individuals with a major airway injury die at the scene
      of the accident, as a result of asphyxia caused by interruption or obstruction of
      the airway, compounded by aspiration of blood and intrapulmonary hemorrhage. A
      neck traumatized patient thoroughly challenges the practitioner's ability to
      coordinate, diagnose, and rapidly formulate a proper method of treatment.

PMID- 9155307
TI  - Fluid resuscitation in the trauma patient.
AB  - Fluid management of the trauma patient can be challenging to the nurse
      anesthetist. Often the Certified Registered Nurse Anesthetist is unaware of the
      total blood loss of a trauma victim (ie, how much blood loss occurred at the
      scene). The anesthetist must quickly assess the patient's vital signs and
      response to fluid replacement to effectively treat the acute blood loss. In
      today's healthcare market, when cost of care is consistently scrutinized, the
      nurse anesthetist must weigh the risks and benefits to a patient when selecting
      fluid therapies. This article outlines current resuscitative theories and fluid
      types available for use in resuscitating the trauma patient.

PMID- 9155308
TI  - Religious restrictions and the trauma patient.
AB  - This article discusses some of the dilemmas the Certified Registered Nurse
      Anesthetist (CRNA) faces when the patient refuses potential life-saving blood
      products or a blood transfusion. Even if the CRNA disagrees with the patient's
      decision, the patient's right to refuse is taken very seriously in the legal
      arena. Without a court order, the patient cannot be forced to receive blood or
      blood products. It would be easier if there were clear guidelines; unfortunately,
      these do not exist. In the past, courts were more likely to agree with the
      anesthesia provider and order the transfusion, even if the patient were
      competent. Today, courts are less likely to do so in these cases. However, there
      are circumstances in which obtaining a court order for the transfusion is more
      predictable, such as if the patient is a child in a true emergency situation, or
      if the patient is pregnant and the fetus is viable.

PMID- 9155309
TI  - Anesthetic drug interactions.

PMID- 9155310
TI  - Technological innovation: retooling for the future.

PMID- 9155311
TI  - Native American Diabetes Project: designing culturally relevant education
      materials.

PMID- 9155312
TI  - Personal illness models of diabetes: preadolescents and adolescents.
AB  - The purpose of this research study was to explore personal illness models of
      preadolescents and adolescents regarding diabetes mellitus. Personal illness
      models were defined as the adolescents' cognitive representations of their
      disease. Sixty children ages 10 to 17 years with a diagnosis of insulin-dependent
      diabetes mellitus were interviewed using a semistructured questionnaire. Data
      were content analyzed for common themes. Although most participants expressed an
      understanding that their disease would last a lifetime, they were hopeful for a
      cure. Participants wanted healthcare professionals to provide strategies for
      controlling blood glucose to prevent future complications. Family and friends who
      followed the same diet as the adolescent with diabetes were viewed as supportive.
      The majority of adolescents were responsible for much of their own disease
      management. Their greatest fears concerned insulin reactions and long-term
      complications such as amputation of limbs.

PMID- 9155313
TI  - Patient perceptions of factors that affect adherence to dietary regimens for
      diabetes mellitus.
AB  - The purpose of this study was to identify how selected factors influence patient
      use of diet regimens for diabetes and to determine the effect of demographic
      characteristics. A survey was conducted using a 75-item questionnaire designed to
      collect responses from people with non-insulin-dependent diabetes mellitus.
      Frequency distributions and chi-square analyses were performed on the survey
      data. Five significant relationships were identified: (1) age and emotions, (2)
      age and schedule, (3) gender and emotions, (4) use of a diet plan and being told
      why to control diet, and (5) use of a diet plan and return for follow-up
      education. Dietitians need to consider demographic characteristics to tailor
      education sessions and to focus on improving communication with patients to
      increase their understanding of diabetes. This study showed that increased
      education promoted increased adherence to dietary recommendations.

PMID- 9155314
TI  - Predictors of adherence to nutrition recommendations in people with non-insulin
      dependent diabetes mellitus.
AB  - The purpose of this study was to determine how the components of psychosocial
      adjustment to diabetes predict adherence to nutrition recommendations based on
      self-reported successful completion of contingency contracts. The relationships
      between the components of psychosocial adjustment and adherence to nutrition
      recommendations were examined in a convenience sample of patients with non
      insulin-dependent diabetes mellitus participating in a contingency contracting
      intervention with nurses. Patients completed a standardized instrument, the
      Diabetes Care Profile, at the time they were enrolled into this randomized
      clinical trial. High and low levels of adherence to nutrition recommendations
      were identified by a median split of the number of contingency contracts
      completed for adherence to nutrition recommendations. Subjects who reported
      higher regimen adherence and a higher support ratio (received more diabetes
      specific social support than desired) were significantly less likely to engage in
      contingency contracting for adherence to nutrition recommendations.

PMID- 9155315
TI  - Hypertension education: an important and neglected part of the diabetes education
      curriculum?
AB  - This review highlights the important role of hypertension education in reducing
      the impact of hypertension on the development and progression of diabetes-related
      complications. Hypertension is commonly associated with diabetes mellitus and can
      significantly affect the progression of the complications of diabetes. Lifestyle
      changes similar to those recommended for diabetes management can result in a
      lowering of blood pressure and can be maintained on a long-term basis to benefit
      patients with diabetes and mild hypertension. Recently, a team approach in a
      hypertension clinic model similar to the team approach for diabetes treatment was
      shown to be effective in diabetes management. Increased awareness of hypertension
      education may contribute greatly to reducing the complications of diabetes.
      Hypertension education should be an important component of the diabetes education
      curriculum.

PMID- 9155316
TI  - Quality of life and social environment as reported by Chinese immigrants with non
      insulin-dependent diabetes mellitus.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) has been associated with
      stressful events such as immigration. The purpose of this paper is to report a
      pilot study that tested translated and back-translated instruments to ascertain
      factors related to diabetes management in a group of Chinese immigrants with
      diabetes. The descriptive, cross-sectional design included a convenience sample
      of 30 Chinese immigrants who had been diagnosed with NIDDM for at least 1 year.
      Consenting participants completed paper- and-pencil questionnaires (Diabetes
      Family-Behavior Checklist II, Diabetes Quality of Life, and MDRTC Knowledge Test)
      that had been translated and back-translated into Chinese and returned them in
      stamped, self-addressed envelopes. Results indicated that most of the scale and
      subscale reliabilities were similar to those published previously. Study
      participants had received limited diabetes education, reported many problems
      managing diabetes, especially in terms of social and vocational issues, and
      reported dissatisfaction with their quality of life. Diabetes-related family
      supportive behaviors were rated positively indicating the importance of including
      family members in educational programs.

PMID- 9155317
TI  - A questionnaire for assessing barriers to healthcare utilization: Part I.

PMID- 9155318
TI  - Nursing assistants: misguided ambition or a hidden political agenda?

PMID- 9155319
TI  - [From charitable activity to profession].

PMID- 9155320
TI  - [Beverly Malone sends a vibrant message to the nurses from Quebec].

PMID- 9155321
TI  - [Vision, passion, reason: the paradoxes of a profession].

PMID- 9155322
TI  - [Where does the health care systems reform take us?].

PMID- 9155323
TI  - [Georgette Banville and community health services, "I deserve no credit. I love
      what I am doing"].

PMID- 9155324
TI  - [Reengineering: a new concept used in emergency triage].

PMID- 9155325
TI  - [Bone marrow transplantation--a new technique. Collection of blood stem cells].

PMID- 9155326
TI  - [The distress of family care givers. Clinical challenge and perspectives for
      research].

PMID- 9155327
TI  - [From clinical observation to research. Effects of music in a neonatal unit].

PMID- 9155328
TI  - [For the reinforcement of quality nursing and obstetric care].

PMID- 9155329
TI  - Is Quebec moving toward professional deregulation?

PMID- 9155330
TI  - [At the cross roads between care and technology].

PMID- 9155331
TI  - [The Internet. Before navigating].

PMID- 9155332
TI  - [Maisonneuve-Rosemont Hospital. Nurses at the center of an integrated follow-up
      of the patients].

PMID- 9155333
TI  - [Promotion and upkeep of breast feeding. The nurses of Monteregie start acting].

PMID- 9155334
TI  - [Self perception: the key stone of nursing interventions with hyperactive
      children].
AB  - Denise Dumas, a nurse at the Hotel-Dieu du Sacre-Coeur de Jesus hospital, in
      Quebec City, and Louise Pelletier, an associate professor at the Ecole des
      sciences infirmieres of Universite Laval, are interested in promoting
      understanding of problems linked to hyperactivity in school-age children. They
      suggest appropriate nursing interventions for child psychiatry units in hospitals
      and outpatient clinics. The authors give a definition of attention-deficit
      hyperactivity disorder, specifying its prevalence, etiology and treatment, and
      describe the behaviour of the hyperactive child. They go on to look at the
      concept of self-perception and deal with its development and its importance in
      children's lives. Most importantly, the authors suggest nursing interventions
      suited to the needs of hyperactive children.

PMID- 9155336
TI  - [The song of Isolde. Deontology and ethics in nursing care, or the meeting of two
      autonomies].

PMID- 9155335
TI  - [The exicting life of Elisabeth Carrier, nurse without borders. Interview by
      Sylvie Vallieres].

PMID- 9155337
TI  - [Nutrition a la carte. Echos of osteoporosis].

PMID- 9155338
TI  - [A relative in a nursing home with memory problems. Health status of care
      givers].

PMID- 9155339
TI  - [A different concept of sex education for adolescents. Is it possible?].

PMID- 9155340
TI  - Environmental Protection through waste management, Implications for staff
      development.
AB  - Increasing public concern is focusing on healthcare providers as a primary source
      of medical waste. As nurses practice in expanded roles in a variety of settings,
      attention must be paid to teaching them how to be ecologically responsible by
      assessing the environmental impact of the services they provide and providing
      ways to reduce the volume of waste.

PMID- 9155342
TI  - Orientation program for a hospital-based dual case manager and educator role.
AB  - The nurse case manager role is continually evolving. Case managers are being
      challenged to perform new functions. There are few articles concerning
      orientation programs for case managers. This article provides a successful
      orientation program and clinical orientation schedule for a unique unit-based
      nurse case manager/educator role. The orientation program is outlined based on
      the four competency domains of the nurse case manager/educator clinical
      expertise, resource management, staff education, and patient/family education.
      Program topics and an orientation schedule are provided.

PMID- 9155341
TI  - Development of the student nurse coordinator role. A shared decision making
      process.
AB  - Using shared decision making, staff nurses designed a new system to support
      student nurses in their learning needs. This new system improved continuity of
      care and patient care follow through and assisted in strengthening relationships
      between the student, unit staff, and clinical instructors.

PMID- 9155343
TI  - The use of focus groups to assist in the design and implementation of a new
      nursing practice model.
AB  - Focus groups facilitate change in healthcare institutions by providing
      comparative perceptions of all levels of healthcare staff in the environment,
      obtaining impressions of new options for healthcare delivery for which no
      information is available, and stimulating new ideas to improve cost-effective
      quality care. The authors discuss their experience using this data gathering and
      evaluation approach during the planning and implementation of a new nursing
      practice model. Factors to consider when using focus groups are offered, and
      lessons learned from the experience are presented.

PMID- 9155344
TI  - Professional advancement model for critical care orientation.
AB  - The Mayo Medical Center, Rochester, Minnesota, has developed a unique
      collaborative method to educate both the experienced and the recent graduate
      nurse about critical care. These programs are 12 to 16 weeks and include a
      classroom, a skills lab, computer-assisted learning, and preceptor instruction.
      The curriculum model design incorporates Benner's novice-to-expert professional
      advancement model. Professional growth of the critical care nurse occurs through
      a combination of educational strategies that build on general theory to the
      application of critical thinking skills. The result of this program is a
      competent, practicing, critical care nurse.

PMID- 9155345
TI  - Perceived competence and actual level of knowledge of diabetes mellitus among
      nurses.
AB  - Staff nurses were surveyed on their perceived and actual level of knowledge of
      diabetes mellitus. Staff nurses (n = 32) employed at a rural 62-bed acute care
      hospital in the southeastern United States constituted a convenience sample. The
      Diabetes Self-Report Tool was used to assess staff nurses' perceptions of
      knowledge of diabetes mellitus. Using a Likert-type scale a mean score of 88% was
      obtained concerning perceived knowledge. The Diabetes Basic Knowledge Test was
      used to measure the actual level of knowledge of diabetes mellitus. A mean score
      of 75% was obtained on the Diabetes Basic Knowledge Test. Nurses' perception of
      knowledge was not related to actual knowledge scores. Study findings raise
      questions for the nurse involved in staff development concerning the adequacy of
      nursing competency validation in the area of diabetes management.

PMID- 9155346
TI  - A systematic plan for nurse educator development.

PMID- 9155347
TI  - Remembering the basics ... again!

PMID- 9155348
TI  - Health care of the internationally adopted child part 1. Before and at arrival
      into the adoptive home.
AB  - International adoptees are frequently encountered in pediatric practice. Their
      health status in the country of origin is quite variable. Once in the United
      States, there is no mandated medical evaluation for these infants and children.
      Commonly missed or ignored conditions include vision or hearing loss, infectious
      diseases, incomplete immunizations, and various allergies and food intolerances.
      The prepared nurse practitioner can provide invaluable assistance in ensuring the
      efficient and appropriate evaluation of each internationally adopted child. Part
      1 of this series discusses concerns before the child's arrival in the adoptive
      home and the medical issues most important soon after arrival Part 2 addresses
      long-term issues including the follow-up of initial assessments, management of
      chronic medical problems, and concerns about growth, development, and social
      adjustments.

PMID- 9155349
TI  - Neonatal nurse practitioner and physician use on a newborn resuscitation team in
      a community hospital.
AB  - INTRODUCTION: Neonatal nurse practitioner (NNP) and physician (NCP) use in a
      community hospital was evaluated to test the hypothesis that NNP availability
      would result in changing patterns of NCP attendance at newborn resuscitations.
      METHOD: Records were reviewed for consecutive years before (pre-NNP) and after
      (post-NNP) NNP employment for frequency of NNP and NCP attendance at moderate-,
      high-, and very high-risk deliveries, together with rates of low Apgar scores and
      resuscitation guideline compliance. RESULTS: Pre-NNP, NCPs attended 39.5% o of
      moderate-risk and 91.6% of high-risk deliveries; these figures fell to 2.1% and
      6.0%, respectively, during post-NNP (chi square: df = l, p < .0001). Post-NNP,
      NNP attendance at moderate- and high-risk deliveries was 88.6% and 99.2% higher
      than NCP attendance during pre-NNP (chi square: df = l, p < .01). No difference
      was observed between periods in rates of Apgar scores less than 7 at 5 minutes or
      the percentage of resuscitations that complied with current guidelines.
      DISCUSSION: In community hospitals NNPs may be used instead of NCPs for moderate-
      and high-risk deliveries. They may also be used more than NCPs in the absence of
      NNPs.

PMID- 9155350
TI  - An asthma management program for urban minority children.
AB  - Morbidity and mortality continue to increase for children with asthma. Minority
      children have disproportionately higher rates of adverse outcomes on almost all
      disease measures. An asthma management program for urban minority children was
      developed with research-based intervention strategies and insights gained from
      the child and family perspectives on illness and health care delivery. The goal
      of the intervention program was to deliver care that was culturally sensitive,
      focused on decreasing barriers to appropriate self-management, and committed to
      promoting partnerships among children, families, the health care system, and the
      broader community.

PMID- 9155351
TI  - Tuberculosis, a pediatric concern.

PMID- 9155352
TI  - Attention-deficit/hyperactivity disorder: focus on pharmacologic management.

PMID- 9155353
TI  - Phytophotodermatitis.

PMID- 9155354
TI  - Children first: expanding health insurance coverage for children.

PMID- 9155355
TI  - Patient education on the Web.

PMID- 9155356
TI  - Effectively incorporating patient education into the primary care setting.

PMID- 9155357
TI  - Review of cerebral palsy, Part I: Description, incidence, and etiology.
AB  - Cerebral palsy (CP) is a nonprogressive disorder of motor function. Although it
      has been recognized for more than a century, much remains unknown regarding its
      etiology. It has been estimated that 17 to 60 percent of the cases of CP have no
      known perinatal or neonatal complications. Undocumented antenatal events may
      cause brain damage or increase the infant's vulnerability to future events. The
      prevalence of CP has remained relatively constant; however, its incidence in the
      preterm population has increased with the improving survival of the very low
      birth weight infant.

PMID- 9155358
TI  - Acyanotic lesions with increased pulmonary blood flow.
AB  - The neonatal nurse is a vital link in the recognition and management of infants
      born with congenital heart disease. This article examines the acyanotic cardiac
      defects with increased pulmonary blood flow: patent ductus arteriosus, atrial
      septal defect, ventricular septal defect, and endocardial cushion defects. The
      hemodynamics, clinical presentation, differential diagnosis, surgical repair, and
      medical management of each defect are presented. Parental teaching needs are
      identified and discussed.

PMID- 9155359
TI  - Pain behaviors in LBW infants accompany some "nonpainful" caregiving procedures.
AB  - Painful procedures may lead to both long- and short-term complications in low
      birth weight (LBW) infants. This study investigated neonatal pain responses
      (grimace, slight cry expression, increased cry expression, and knee/leg flexion)
      during six painful and three nonpainful procedures. The 30 LBW infants studied
      were less than 48 hours of age and less than 34 weeks gestation, with a mean
      birth weight of 1,320 gm. The design was comparative; data analysis included
      repeated measures of analysis of variance, independent t-tests, and paired t
      tests. The four pain responses were found to be present 75 to 100 percent of the
      time after painful procedures (suctioning, skin puncture, dressing change or
      removal, discontinuation of intravenous line, and insertion of a nasogastric
      tube). They were also found to be present 49 to 69 percent of the time after
      nonpainful procedures (total position change, addition/withdrawal of fluid from
      umbilical catheter, and IV administration of medication).

PMID- 9155360
TI  - Implementing an immunization program in the neonatal intensive care unit.
AB  - The immunization of children less than two years old is a priority with several
      organizations involved in health care. The infants in the intensive care nursery
      and their parents provide a ready population with whom to implement immunization
      programs. This article reviews the importance of immunizations for the newborn
      and their appropriateness in the intensive care setting. Suggestions are also
      made for implementing this concept in the normal new-born nursery, utilizing
      Lewin's change theory.

PMID- 9155361
TI  - Pacifiers in the NICU: a lactation consultant's view.
AB  - Many infants, especially premature infants, may benefit from the regular use of
      pacifiers in the NICU. The NICU nurse who has a variety of pacifiers to choose
      from can select the one that best meets the infant's needs. But although mother's
      milk at the breast may not be the choice of all mothers, or may not be an option,
      it ought to be viewed as the norm. Full-term infants at the breast generally do
      better with no pacifiers at all. For the NICU patient, smooth transition to
      successful oral feedings at the breast or bottle is an important step in the
      direction of home.

PMID- 9155362
TI  - Medical, developmental, and pharmacologic intervention: the essence of
      collaboration.

PMID- 9155363
TI  - Assessment of fetal lung maturity.

PMID- 9155364
TI  - Research utilization: handling preterm infants in the NICU.

PMID- 9155366
TI  - Paediatric nursing.

PMID- 9155367
TI  - Shooting for the stars--towards excellence in paediatric nursing care.

PMID- 9155365
TI  - Using airway graphics to optimize mechanical ventilation in neonates with
      respiratory distress syndrome.

PMID- 9155368
TI  - Innovations in paediatric children's assessment unit and developing outreach
      service.

PMID- 9155370
TI  - Publishing workshops number 3. Preparing a manuscript: reporting qualitative
      research findings.

PMID- 9155369
TI  - "Once upon a time ..." story telling: a paediatric perspective.

PMID- 9155371
TI  - The mysteries of the Milton Tank!
AB  - In today's health care environment, one is often confronted with arguments for
      and against the casualisation of nursing staff in our hospitals. The question is,
      can one nurse really so easily replace another? What do we really know about the
      experienced nurse changing jobs? The author uses her personal experience-her
      transition from adult to paediatric nursing-to describe the difficulties
      associated with nursing in vastly different areas. Supported by nurse theorist
      Patricia Benner's ideas on skill and competence levels (1984), the author
      recounts the crisis in confidence she experienced when confronted with the
      paediatric "culture". Also discussed are the ways in which paediatric nursing
      knowledge develops (in this country it develops very much on the job) and the
      implications this has for staffing.

PMID- 9155372
TI  - Parents' expectations of the nurse-role negotiation.

PMID- 9155373
TI  - Factors in stress and burnout among paediatric nurses in a general hospital.
AB  - High stress and staff turnover in a multispecialty paediatric area prompted this
      study that aimed to: 1) measure the burnout level of nurses in a multi-specialty
      paediatric area 2) identify and validate causes of stress 3) identify new ways of
      preventing stress on the ward. Fifty-four percent (n = 14) of the paediatric
      nurses completed a questionnaire booklet that included demographic data, the
      Maslach Burnout Inventory, the Nursing Situations Questionnaire, the Hopkins
      Symptom Checklist-21, the Ways of Coping Checklist and open-ended questions about
      sources of stress and satisfaction at work. Results indicated levels of burnout
      and distress comparable with larger studies. Conflict with doctors was the major
      source of stress, followed by workload, inadequate preparation in dealing with
      the emotional needs of patients and their families and death and dying. Conflict
      with doctors has not previously been identified as the major source of stress.
      However, workload and death and dying are commonly identified as sources in the
      literature. Suggestions for further research and the low response rate are
      discussed.

PMID- 9155374
TI  - The ethics of research in the neonatal intensive care unit.

PMID- 9155375
TI  - The sick child, humanitarian narratives and the getting of hospitals: an
      historical research brief.
AB  - The nineteenth and early twentieth century discourse on the need for a separate
      children's pavilion at Dunedin Hospital, and for a fever hospital, constructed
      "the sick child' as an image of suffering. This research brief offers a
      preliminary consideration of the way in which this construction relates to Thomas
      Laqueur's "humanitarian narrative" (1989). It examines five texts to see how "the
      sick child' was used in a persuasive discourse to get hospitals.

PMID- 9155376
TI  - Introducing Ruth McNeur. Interview by Joc Parkes.

PMID- 9155377
TI  - Introducing Gail Anderson, nee Rogers.

PMID- 9155378
TI  - Moral decision-making of nurses working with children in hospital.

PMID- 9155379
TI  - An investigation of nurses' knowledge and decision-making in relation to
      childrens' pain and its management.

PMID- 9155380
TI  - How a nurse beat psoriasis by moving to a different climate. Interview by Rodney
      Porter.

PMID- 9155381
TI  - Speaking with the enemy.

PMID- 9155382
TI  - International brigade.

PMID- 9155383
TI  - Hell's belles.

PMID- 9155384
TI  - Danger zones.

PMID- 9155385
TI  - B fit or B flat. Interview by Neil Crossley.

PMID- 9155386
TI  - Full of beans.

PMID- 9155387
TI  - It's a duet not a duel.

PMID- 9155388
TI  - Mugged by the system.

PMID- 9155389
TI  - Spell check.

PMID- 9155390
TI  - Better by degrees.

PMID- 9155391
TI  - Unity is strength in joint research project.
AB  - The advent of the purchaser/provider split produced a number of challenges for a
      coordinated approach to supporting research. This article describes a
      collaboration between North Derbyshire Health Commission and Chesterfield and
      North Derbyshire Royal Hospital NHS Trust in bringing together purchaser and
      provider. A research interest group spanning purchaser and provider organisations
      has been responsible for a number of initiatives including training days, a
      research database and a resource pack for would-be researchers which aim to raise
      the profile of research across North Derbyshire.

PMID- 9155392
TI  - Post-mortems: how and why they are carried out.
AB  - This article looks at the use of data from post-mortems, of reasons why certain
      deaths are referred to the coroner and how the bodies are dealt with. The post
      mortem procedure is also described.

PMID- 9155393
TI  - Rheumatology. Professional issues.

PMID- 9155394
TI  - Hard graft.

PMID- 9155396
TI  - Equipped to care.

PMID- 9155395
TI  - Light relief.

PMID- 9155397
TI  - Know how. Four-layer bandaging.
AB  - The concept of four-layer bandaging originated in the 1980s at Charing Cross
      Hospital, London. Since then, a second four-layer system in kit form has been
      developed. The results of a recent trial involving 232 patients showed that the
      two systems have equivalent healing. Today, four-layer bandaging is a popular
      compression regime, and is used in a wide range of health-care settings. Ease of
      application of the bandages, and reproducibility, mean that it is not only a
      therapeutic technique but a very safe one.

PMID- 9155398
TI  - When healing is a pain.

PMID- 9155400
TI  - A critical difference.

PMID- 9155399
TI  - Not yet cut and dried.

PMID- 9155401
TI  - Immune-enhancing enteral formulas in critically ill patients.

PMID- 9155402
TI  - Immune-enhancing enteral formulas: are they beneficial in critically ill
      patients?
AB  - Over the last decade there has been considerable interest in the use of specific
      nutrients to alter the metabolic response to injury and infection, to improve
      immune function, and to prevent or reverse the severe catabolism and wasting of
      the lean body mass that accompanies critical illness. In this review,
      representative animal studies and, when available, human studies examining the
      potential benefits of these individual nutrients are summarized. The overview of
      basic investigations is by no means all-inclusive, and the emphasis of this
      manuscript is a review of the currently available clinical trials examining the
      potential benefits of combinations of these individual immunity-enhancing
      nutrients in human patients.

PMID- 9155403
TI  - Nutrition management in a pregnant comatose patient.
AB  - Major intracranial injury or disease during pregnancy resulting in a comatose
      state presents unique and complex management challenges. Our patient is a 34-year
      old woman who suffered a closed-head injury associated with spousal abuse at 22
      weeks' gestation. This injury resulted in a large right frontoparietal hematoma
      that was subsequently evacuated via a right frontotemporal craniotomy 5 days
      after the injury. She remained in a vegetative state postoperatively. Aggressive
      nutrition support was provided with enteral feedings through a nasoduodenal
      feeding tube. Mild oligohydramnios was detected at 30 weeks' gestation and was
      subsequently determined to be due to preterm premature rupture of membranes. She
      was managed until 33 weeks' gestation, when signs of chorioamnionitis were noted.
      She then underwent a primary cesarean delivery and was delivered of an
      appropriate-for-gestational-age 2150-g viable male infant. The patient had
      progressive improvement in her mental status with occupational and physical
      therapy and was discharged on the 29th postpartum day. This case presents the
      nutrition and medical challenges of maintaining adequate maternal and fetal
      health in a pregnant comatose patient.

PMID- 9155404
TI  - Clinical management of latex allergy.
AB  - The use of latex gloves in the health care setting dates back to the 1800s, when
      these products were introduced as a means of preventing the passage of
      microorganisms to operating room patients. Today, fear of human immunodeficiency
      virus transmission and other blood-borne diseases has led to implementation of
      standardized guidelines for glove use for health care professionals. Because of
      the unique combination of strength, flexibility, and elasticity of natural
      rubber, latex is typically the material of choice for a variety of medical
      products, including examination gloves. Unfortunately, routine use of latex in
      the health care setting may be detrimental to patients and caregivers with a
      history of natural rubber latex hypersensitivity reactions.

PMID- 9155405
TI  - Banana flakes control diarrhea in enterally fed patients.
AB  - Diarrhea occurs frequently in the critically ill tube-fed population and may
      result from a multitude of causes. Despite the availability of antidiarrheal
      medications, diarrhea associated with enteral feedings remains a problem for
      clinicians and for the patients affected by it. We tested the hypothesis that
      administration of banana flakes would control diarrhea in critically ill patients
      receiving enteral feedings. Thirty-one patients with diarrhea and receiving
      enteral feedings were randomized to receive either banana flakes or medical
      treatment for diarrhea. Medical treatments included the use of pharmacological
      agents according to the discretion of the patient's physician or reducing feeding
      rates. Both banana flakes and medical treatments reduced the severity of diarrhea
      in critically ill tube-fed patients. Over the course of treatment, mean diarrhea
      scores were 21.64 +/- 7.81 for the banana flake group and 25.41 +/- 9.76 for the
      medical group. These differences were not statistically significant. Both groups
      achieved similar levels of nutrition support. The banana flake group had less
      diarrhea clinically, with 57% of the subjects diarrhea free on their last study
      day as opposed to 24% of the medically treated subjects. This occurred despite a
      threefold increase in the number of patients testing positive for Clostridium
      difficile toxin in the banana flake group. We conclude that banana flakes can be
      used as a safe, cost-effective treatment for diarrhea in critically ill tube-fed
      patients. Banana flakes can be given concurrently with a workup for C. difficile
      colitis, thereby expediting treatment of diarrhea.

PMID- 9155406
TI  - Clinical pathway for pediatric parenteral nutrition.
AB  - The nutrition support team at Lucile Salter Packard Children's Hospital at
      Stanford developed a clinical pathway for infants and children receiving
      parenteral nutrition (PN). Use of clinical pathways for health care delivery is
      one way in which clinicians and institutions are responding to pressure from
      managed care organizations to reduce costs and maintain or improve quality. This
      pathway was developed to standardize the process for ordering, implementing, and
      monitoring PN. Specific goals for the pathway are as follows: to decrease the
      number of patients receiving PN inappropriately, to decrease the duration of PN
      for those patients who require it, to determine complication rates, and to
      monitor outcomes of therapy. Such comprehensive monitoring will help identify
      areas for improvement. By developing and implementing action plans to address
      these issues, we expect to improve continuously the processes and outcomes
      associated with PN therapy.

PMID- 9155407
TI  - Nutrition requirements in patients with toxic epidermal necrolysis.
AB  - Patients with toxic epidermal necrolysis, a severe, exfoliative skin disorder,
      have clinical features similar to those of partial-thickness burn patients. The
      literature suggests that they also have similar nutritional requirements. We
      report two patients diagnosed with toxic epidermal necrolysis on mechanical
      ventilation, in whom resting energy expenditure and respiratory quotient were
      measured by indirect calorimetry. The patients were treated using standard burn
      protocols. Nitrogen balance was calculated by measuring total urinary nitrogen in
      urine samples obtained over 24 hours. These measurements were done while the
      patients were on mechanical ventilation and receiving total parenteral nutrition.
      As in burn patients, early in their course the two patients had resting energy
      expenditure values twice that predicted. After 12 days of hospitalization,
      nitrogen balance was negative in patient 1 and positive in patient 2. Energy and
      protein requirements appear to have been related to the amount of body surface
      affected.

PMID- 9155408
TI  - Vitamin shortage, plasmodium, and the crab nebulae: a Web odyssey.

PMID- 9155409
TI  - More information on phantom limb pain and to urge orthopaedic nurses to take an
      active role in prevention of this problem.

PMID- 9155410
TI  - Fracture blisters: a review of the literature.
AB  - Following orthopaedic trauma, fracture blister formation creates a disruption in
      skin integrity for the injured patient and unique care challenges for the nurse
      and physician. These blisters may delay surgery, alter the optimum treatment
      plan, promote wound infection, delay wound healing, and ultimately prolong
      recovery. This article presents a review of the current literature and includes a
      discussion of the anatomy of the skin, pathophysiology of fracture blisters, and
      a review of current research. The complications, prevention, treatment, and
      implications for nursing care are also examined.

PMID- 9155411
TI  - Networking for nurses in today's turbulent times.
AB  - Networking is a critical component for any nurse's success in today's turbulent
      times. Traditionally seen as a skill set reserved for nurse executives,
      proficient networking abilities must now be developed by nurses at all levels.
      Cultivating a diverse network of people and being able to use it wisely will make
      a difference for many nurses in their careers. Once a luxury for augmenting one's
      professional development, networking has become a required component for
      successfully managing the rapidly changing health care environment nurses face
      every day.

PMID- 9155412
TI  - Acute management of patients with hip fracture. A research literature review.
AB  - PURPOSE: To provide the orthopaedic nurse a summary of the significant research
      concerning the management of patients with a fractured hip. DESIGN: Meta
      Analysis. SAMPLE: 135 articles reviewed for possible inclusion, 57 original
      research reports and publications are reported. METHODS: For the years 1985 to
      March 1996 Medline, MEDLARS, and CINAHL data bases were searched. Twenty-seven
      search terms were used, including hip fractured), orthopedic standards, and
      length of stay. MAIN RESEARCH CLASSIFICATIONS: Preoperative, Operative and
      Postoperative. Studies arranged by author, outcomes, focus, data source and year,
      sample, and findings. FINDINGS: Research reports were found concerning:
      preoperative care including the use of MRI, predictors of complications and
      transfusion needs, and impact of skin traction on pain; operative studies
      including spinal anesthesia and oxygen saturation rates, use of blankets to keep
      patient warm, prophylactic antibiotic use, and impact of delaying surgery; and
      postoperative reports including the incidence of DVT, nutritional status,
      cauterization, management protocols, morbidity and mortality risks, length of
      stay, functional status, and ambulation. CONCLUSION: The scientific merit of each
      study was not evaluated in depth. With some degree of comfort the review did find
      one study or several studies to support the findings presented. IMPLICATIONS FOR
      NURSING RESEARCH: Current research concerning the impact of pressure sores,
      incontinence, management of falls risk, and the impact the fear of falling on
      postinjury patients are just a few of the topics not adequately addressed.

PMID- 9155413
TI  - From bed to chair. Transferring the non-weight-bearing patient.

PMID- 9155414
TI  - Caring for the adult patient undergoing anterior/posterior spinal fusion.
AB  - Adult patients with severe scoliosis are increasingly undergoing a combined
      anterior/posterior spinal fusion to correct the spinal deformity. If the
      scoliosis is thoracolumbar, a retroperitoneal approach and a thoracotomy are
      required. This combined surgical approach requires increased knowledge and
      assessment skills of the attending nurse. Included in this article is the
      preoperative, intraoperative, and postoperative management of the adult patient
      undergoing anterior/posterior spinal fusion.

PMID- 9155415
TI  - Care of the arthroscopy patient with noncardiogenic pulmonary edema.
AB  - A young athlete is unexpectedly admitted to an orthopaedic unit after routine
      arthroscopic knee surgery with the following diagnosis: noncardiogenic pulmonary
      edema related to postextubation laryngospasm. This emergent condition, which may
      be life-threatening due to rapid changes in intrathoracic, alveolar, and
      interstitial pressures, requires immediate, aggressive treatment. With proper
      intervention, laryngospasm-induced noncardiogenic pulmonary edema becomes a self
      limiting process, and full recovery may occur within 48 hours of the initial
      insult to the lungs. This article presents a case study of a patient with this
      condition, including the initial and subsequent interventions that were provided.
      The pathophysiologic responses and clinical manifestations of laryngospasm and
      noncardiogenic pulmonary edema are addressed, followed by a suggested course of
      treatment.

PMID- 9155416
TI  - Suggestions for a competency-based orientation for an orthopaedic unit.
AB  - Effective orientation programs should provide new RN and LPN employees with very
      specific performance expectations. Competency-based orientation provides such a
      structure. This approach not only decreases the orientee's anxiety, but it also
      acts as a basis for establishing competencies specific to that unit. Because the
      existing staff members are intimately involved in the process, socialization
      within the unit and cohesiveness of purpose are enhanced. Adult learning theory,
      educational principles, self-paced learning modules, and the use of preceptors
      and check-off lists are employed in this Competency-Based Orientation (CBO)
      program for an adult orthopaedic unit. Samples of various aspects of a CBO are
      included.

PMID- 9155417
TI  - Neer classification of fractures of the proximal humerus.

PMID- 9155418
TI  - Ethical questions inherent in compliance.
AB  - Promoting patient compliance is considered to be good clinical practice. However,
      compliance conveys a sense of being submissive or obedient to another; therefore,
      promoting compliance becomes a paternalistic action. The author uses a clinical
      situation to demonstrate some of the ethical questions related to compliance
      (i.e., who decides, who knows best, and how noncompliant patients are treated)
      and discusses these questions using the ethical precepts of doing no harm and
      respecting autonomy.

PMID- 9155419
TI  - Historical developments in the drug therapy of diabetes.
AB  - It is suggested that some 16 million Americans have diabetes, although about only
      one-half of them are diagnosed. Type I or IDDM diabetics must take insulin in
      some form to maintain their life. A larger number of Americans have Type II or
      NIDDM, and many can be treated with a combination of diet and exercise. Many of
      the Type II diabetics will need to take oral medications at some point in their
      life and a somewhat smaller number may find that they must use insulin injections
      if they are to maintain good control of their diabetes. This article describes
      the historical events leading up to the present therapeutic options for both Type
      I and Type II diabetics. Also included is a list of drugs that are in the
      research phase at the present time as well as a list of internet sites where the
      practitioner and patient alike can keep up to date on new developments in the
      treatment of diabetes.

PMID- 9155421
TI  - Proceedings of selected papers from the NAON 1996 Fall Case Management
      Conference. New Orleans, Louisiana, November 14-16, 1996.

PMID- 9155422
TI  - The evolving of the United States health care delivery system.

PMID- 9155423
TI  - Types of case management.

PMID- 9155424
TI  - Office nursing case management.

PMID- 9155425
TI  - Home health care management.

PMID- 9155426
TI  - Workers' compensation.

PMID- 9155427
TI  - Perioperative DVT and pulmonary embolism. Diagnosis, management, and treatment.

PMID- 9155428
TI  - Case management: a joint effort. Where do you start?

PMID- 9155429
TI  - Case management of the patient with arthritis.

PMID- 9155430
TI  - Clinical pathways for a patient with a total joint replacement.

PMID- 9155431
TI  - Case management through a multidisciplinary spinal evaluation.

PMID- 9155432
TI  - Case management and clinical pathways for the pediatric orthopaedic patient.
AB  - Clinical pathways are for predictable, routine, high volume kinds of patients and
      procedures. Case management is a strategy that is for unpredictable, complex,
      high cost/high risk kinds of patients.

PMID- 9155433
TI  - Paving the way. Outcome planner for the orthopaedic patient at home.
AB  - The home care nurse often spent more time documenting than actually caring for
      the patient. The decision was made to streamline documentation, and our road to
      outcome planners began.

PMID- 9155436
TI  - Issues of cost and reimbursement. What does our future hold?

PMID- 9155434
TI  - Clinical pathways. Designing road MAPs for outcomes management across the
      continuum of care.

PMID- 9155435
TI  - Critical pathways: the next generation of outcomes tracking.
AB  - In summary, for each critical path you should have financial, quality, variance
      analysis, health-related quality of life and patient satisfaction outcome
      measures that should be reported as a package in a frequency established by the
      organization. These measures must complement the overall critical path program
      goals and objectives. The data must also be provided to the critical path teams
      to analyze and define where there may be opportunities for improvement. This puts
      the data analysis and responsibility of care processes into the hands of the
      clinicians where it belongs and not with administration. Administration provides
      the vehicles for the data; the clinicians provide the analysis.

PMID- 9155437
TI  - [Ethics in nursing].

PMID- 9155438
TI  - [The Amstetten hospital: "Baby-Friendly hospital--nursing friendly hospital"].

PMID- 9155439
TI  - [Expert opinion. Preparation and execution of apparatus-assisted autotransfusion-
      "Cell saver"--by the nursing service at the intensive care department].

PMID- 9155440
TI  - [The discussion of ethics in nursing].

PMID- 9155441
TI  - [Ethics in routine neonatology--a question of respect and responsibility].

PMID- 9155442
TI  - [Ethics in intensive care units. Ethical values can not be proven--they can only
      be explained].

PMID- 9155443
TI  - [Ethics in nursing and in nursing research].

PMID- 9155444
TI  - [The importance of ethics teaching in the course of nursing education. Ethics
      should be integrated into nursing education].

PMID- 9155445
TI  - [The number of latex allergies is rising rapidly, but--there is no reason for
      latex phobia].

PMID- 9155446
TI  - [Visit with Dr. Franziska Stengel in Vienna: "only a trained brain will be able
      to keep working"].

PMID- 9155447
TI  - [Palliative care and assistance for the dying in Canada, The Netherlands and
      Great Britain. How are the others doing it?].

PMID- 9155448
TI  - [Decubitus ulcer in a patient with multiple sclerosis: the "coordinated care"
      model with moist wound care causes healing within four months].

PMID- 9155449
TI  - [Healing naturally with propolis. With bee propolis to new health].

PMID- 9155451
TI  - [Nursing personnel visiting Pflegezeitschrift].

PMID- 9155450
TI  - [Series Self Care for Nurses: Tips for a pampering day].

PMID- 9155452
TI  - [The importance of the living space for the aged. Old trees should not be
      transplanted].

PMID- 9155453
TI  - [ISO series for seniors accommodations. 1. Consideration of the client's needs is
      the ulterior law].

PMID- 9155454
TI  - [Holidays and their celebration in the home for the aged. Stumbling blocks
      against every day routine].

PMID- 9155455
TI  - Patients' views of day-case cardiac catheterisation.
AB  - Cardiac catheterisation can be performed successfully as a day-case procedure. A
      reduction in the time spent in hospital limits the time available for
      consultation between patients and hospital staff. Research into patient opinions
      and levels of satisfaction can help improve patient care and evaluate the
      effectiveness of changes to care.

PMID- 9155456
TI  - Understanding attitudes towards tissue donation.
AB  - Nurses discussing organ or tissue donation with patients and their relatives need
      to be well informed. Tissue donation is not being optimised. The attitude of
      health professionals towards organ and tissue donation can influence the
      relatives' decision.

PMID- 9155457
TI  - Guidelines for preventing thromboembolism.
AB  - Clinicians, units and hospitals in the UK should develop written policies for
      thromboembolic prophylaxis. Deep-vein thrombosis is both life-threatening and
      costly. The use of prophylaxis should be included in clinical audit and plans for
      patient care. The implementation of research-based and agreed guidelines can
      reduce the incidence of postoperative deep-vein thrombosis.

PMID- 9155458
TI  - Minor burns and hand burns: comparing treatment methods.
AB  - As nurse-led wound management increases, nurses need to maintain research-based
      practice. Water vapour-permeable fabrics cause less accumulation of fluid than
      polythene when used in minor burns. Honey has been used in wound cleansing for
      many years.

PMID- 9155459
TI  - The management of acute asthma.
AB  - Health professionals likely to come into contact with people experiencing an
      acute episode of asthma, such as school nurses, ambulance personnel and A&E
      staff, need clear guidelines on management. The British Thoracic Society
      guidelines, revised this year, advise on the categorisation of asthma, assessment
      and treatment.

PMID- 9155460
TI  - Changing the culture of care for dying patients.
AB  - A care setting's culture will affect the roles played by nurses and people who
      are dying. The theory of malignant social psychology developed in dementia care
      can provide insight into the treatment of dying people. A major cultural shift is
      required if the needs of dying people are to be met and the balance of power
      altered.

PMID- 9155461
TI  - Benign prostatic hyperplasia.
AB  - Benign prostatic hyperplasia is a common problem in men over 50, causing
      unpleasant symptoms. This Update examines the range of treatments now available,
      including traditional interventions and modern techniques.

PMID- 9155462
TI  - Dengue fever.
AB  - Dengue fever, and its more serious haemorrhagic form, is increasingly being found
      among UK travellers to tropical and sub-tropical countries. This Update examines
      transmission, the main symptoms and nursing care of affected people.

PMID- 9155463
TI  - Pressure support systems for hospital use.
AB  - The range of pressure support systems is constantly increasing. Accurate
      assessment will assist the selection process. Practical considerations and cost
      implications must also be taken into account when selecting a product.

PMID- 9155464
TI  - Client assessment in practice.

PMID- 9155466
TI  - [The determinators in decision making].

PMID- 9155467
TI  - [Learning to decide].

PMID- 9155468
TI  - [Ethics of decision making. Methodology].

PMID- 9155465
TI  - [Decision--a philosophical approach].

PMID- 9155469
TI  - [Involvement in health-related choices].

PMID- 9155471
TI  - [Management autonomy].

PMID- 9155470
TI  - [Hospital reform. New decision-making authorities].

PMID- 9155472
TI  - [Stopping treatment in intensive care].

PMID- 9155473
TI  - [The education of nurses' aides].

PMID- 9155474
TI  - [Study of resources; an optional modal].

PMID- 9155475
TI  - [Evaluating professional life situations. Les Membres du Groupe de Travail].

PMID- 9155476
TI  - [Teaching in Siberia].

PMID- 9155477
TI  - [Higher nursing education in Russia].

PMID- 9155478
TI  - [Combination of the results of the national CEFIEC investigation].

PMID- 9155479
TI  - [At the heart of the reform are contracts].

PMID- 9155480
TI  - [The skin. Anatomic and physiological review].

PMID- 9155482
TI  - [Infantile eczema].

PMID- 9155481
TI  - [Pediatric dermatology. Diagnostic methods].

PMID- 9155483
TI  - [Nursing care at the level of a pediatric dermatological consultation].

PMID- 9155484
TI  - [Psycho-traumatic syndromes in children. Clinical aspects].

PMID- 9155485
TI  - [The psycho-affective development in children].

PMID- 9155486
TI  - [Adolescence and myopathy. The changing body].

PMID- 9155487
TI  - [A project in health education. National education in emergency care].

PMID- 9155488
TI  - [Children caught between different advice].

PMID- 9155489
TI  - Periodicity of eating and human health: present perspective and future
      directions.

PMID- 9155490
TI  - Eating frequency: methodological and dietary aspects.
AB  - It is commonly stated that 'snack' foods provide 'empty calories' and, therefore
      elevate energy intake whilst providing insignificant quantities of other
      nutrients. The data presented in the present review suggest that foods which
      contribute to the pattern of 'snacking' contribute significantly to the nutrient
      quality of the diet. Those who 'snack' frequently tend to eat more food in
      general. Part of the difficulty in identifying the nutritional implications of
      'snacking' is related to the definitions of 'meals' and 'snacks' and subsequent
      categorization of individual patterns. The physiological definitions typically
      relating to energy content or the time of eating do not necessarily coincide with
      colloquial, cultural or individual perceptions of what constitutes a 'meal' or
      'snack'. Clearly, a more consistent approach would facilitate interpretation of
      the literature and enable more effective health education messages about
      'snacking' to be delivered.

PMID- 9155491
TI  - Cultural aspects of meals and meal frequency.
AB  - The present paper presents a certain number of cultural elements which interact
      in the determination of the frequency of food intake. Approaches from various
      perspectives (historical, ethnological, anthropological, sociological) draw
      attention to two major aspects relating to the periodicity of food intake: the
      extreme cultural diversity and the continual modifications which have occurred
      over time and space. The various cultural models change and are subject to
      multiple influences, for example, cross-cultural, economic and historical. In
      addition, there are interactions between the models. The definitions of food
      intake and frequency play a major role in building up consumers' perceptions.
      These various perceptions are multiple (perception of self, of food and its
      virtues, the rules and moral values of consumption) and finally influence
      behaviours. Finally, and taking into account the systems of beliefs, the very
      nature of feeding behaviours may carry feelings of guilt for the subject. The
      study of real behaviours and their relationship with health is still incomplete
      for reasons of methodology and also of conceptual definition. In future, data
      collection has to take into account real behaviour as well as subjective
      perceptions and value judgements. A specific effort has to be made in the future
      to develop methodology. This should allow the collection of reliable data and
      particularly comparisons between studies, without oversimplifying and distorting
      cultural specificities.

PMID- 9155492
TI  - Chronobiology and meal times: internal and external factors.
AB  - Although homeostatic mechanisms remain of utmost importance, rhythmic changes are
      present also. The main ones have a period of 24 h (circadian) or about 2-3 h
      (ultradian). Circadian rhythms are derived from a body clock, found in the base
      of the brain, and from the pattern of our sleep-wake cycle, including activity
      and meal times. These rhythms promote the regular changes between an active wake
      period and a recuperative sleep period. Ultradian rhythms are also widespread and
      reflect external (lifestyle) and internal factors. The internal factors include
      biochemical need and some sort of oscillator; but details of how many
      oscillators, and exactly where they are, remain to be established. Food intake,
      appetite, digestion and metabolism have been shown to illustrate these
      principles. Moreover, these principles become important when special
      circumstances exist as far as meal times are concerned; the particular
      difficulties of night workers is a good example.

PMID- 9155493
TI  - Socio-cultural determinants of meal size and frequency.
AB  - Total energy intake and the frequency and size of meals are profoundly influenced
      by the socio-cultural context in which it occurs. Simply eating with one other
      person increases the average amount ingested in meals by 44% and with more people
      present the average meal size grows even larger. The impact of social
      facilitation of energy intake on the individual appears to result from genetic
      effects both on the individuals' sensitivity to the presence of other people and
      also on the number of other people an individual tends to eat with. Culture
      markedly affects the choice of foods in the diet and the pattern of meals over
      the day. However, many of the social, psychological and physical variables that
      influence intake are similar across cultures.

PMID- 9155494
TI  - Meal frequency and energy balance.
AB  - Several epidemiological studies have observed an inverse relationship between
      people's habitual frequency of eating and body weight, leading to the suggestion
      that a 'nibbling' meal pattern may help in the avoidance of obesity. A review of
      all pertinent studies shows that, although many fail to find any significant
      relationship, the relationship is consistently inverse in those that do observe a
      relationship. However, this finding is highly vulnerable to the probable
      confounding effects of post hoc changes in dietary patterns as a consequence of
      weight gain and to dietary under-reporting which undoubtedly invalidates some of
      the studies. We conclude that the epidemiological evidence is at best very weak,
      and almost certainly represents an artefact. A detailed review of the possible
      mechanistic explanations for a metabolic advantage of nibbling meal patterns
      failed to reveal significant benefits in respect of energy expenditure. Although
      some short-term studies suggest that the thermic effect of feeding is higher when
      an isoenergetic test load is divided into multiple small meals, other studies
      refute this, and most are neutral. More importantly, studies using whole-body
      calorimetry and doubly-labelled water to assess total 24 h energy expenditure
      find no difference between nibbling and gorging. Finally, with the exception of a
      single study, there is no evidence that weight loss on hypoenergetic regimens is
      altered by meal frequency. We conclude that any effects of meal pattern on the
      regulation of body weight are likely to be mediated through effects on the food
      intake side of the energy balance equation.

PMID- 9155495
TI  - Carbohydrate tolerance and food frequency.
AB  - Dietary and pharmacological approaches to slowing the rate of glucose absorption
      and blunting the insulin response show promise in the treatment of diabetes and
      hyperlipidaemia. These approaches include dietary fibre, low-glycaemic-index
      foods and gastrointestinal digestive enzyme inhibitors. One common feature is
      that they spread the nutrient load over time. A potentially simpler approach is
      to take more frequent smaller meals over a longer period of the day. Early
      studies suggested that frequent glucose and insulin administration to diabetic
      patients improved diabetes control. More recent acute studies of one test meal or
      1 d blood metabolite profiles have identified a significant economy in insulin
      secretion when glucose is sipped or when meal frequency is increased in both
      diabetic or non-diabetic subjects. In diabetic subjects improvement in mean blood
      glucose levels has also been reported. However, despite the demonstration of an
      alteration in response over time in glucose tolerance in healthy volunteers, no
      longer-term improvement in glycaemic control was reported in the only study in
      diabetes to examine a change from three to nine meals daily over a 1-month
      period. The disparity between longer-term and acute studies requires further
      investigation. At present, although this nutritional approach holds considerable
      theoretical promise, specific advice is premature.

PMID- 9155496
TI  - Meal frequency and plasma lipids and lipoproteins.
AB  - Epidemiological data suggesting benefits of increased meal frequency on CHD risk
      and lipid and lipoprotein levels may be flawed because of biases associated with
      the method of data collection. In normolipidaemic individuals increasing meal
      frequency from three to six or more meals daily over a period of several weeks
      appears to be associated with reduced levels of total and LDL-cholesterol,
      possibly due to reduced cholesterol synthesis or enhancement of reverse
      cholesterol transport. However, in non-obese individuals with polygenic
      hyperlipidaemia and non-insulin-dependent diabetes, altered meal frequency does
      not appear to confer similar benefits. The reasons for the different responses in
      these groups of subjects is not clear. The reported effects of altered meal
      frequency on diurnal levels of triacylglycerols and fatty acids are more
      variable, with benefits being reported principally in association with meal
      frequencies exceeding those which might be translated into practical
      recommendations. Present data preclude recommendations concerning meal frequency
      on the basis of effects on lipids and lipoproteins. Even in healthy individuals
      amongst whom benefits have been observed, the periods of observation have been
      relatively short and it is not known whether adaptation occurs. Further research
      should focus on longer-term studies in healthy individuals as well as
      hyperinsulinaemic and diabetic subjects. For those individuals choosing to have a
      large number of small meals each day, it is relevant to emphasize that no
      untoward effects of increased meal frequency on lipids or lipoproteins have been
      demonstrated.

PMID- 9155497
TI  - Effect of meal frequency and timing on physical performance.
AB  - Two areas of sports nutrition in which the periodicity of eating has been studied
      relate to: (1) the habitually high energy intakes of many athletes, and (2) the
      optimization of carbohydrate (CHO) availability to enhance performance. The
      present paper examines how the timing and frequency of food and fluid intake can
      assist the athlete and physically-active person to improve their exercise
      performance in these areas. Frequent eating occasions provide a practical
      strategy allowing athletes to increase energy intake while concomitantly reducing
      the gastric discomfort of infrequent large meals. The optimization of CHO stores
      is a special challenge for athletes undertaking prolonged training or competition
      sessions. This is a cyclical process with post-exercise CHO ingestion promoting
      muscle and liver glycogen re-synthesis; pre-exercise feedings being practised to
      optimize substrate availability and feedings during exercise providing a readily
      available source of exogenous fuel as endogenous stores become depleted. The
      timing and frequency of CHO intake at these various stages are crucial
      determinants for optimizing fuel availability to enhance exercise capacity.

PMID- 9155498
TI  - Psychological effects of snacks and altered meal frequency.
AB  - Over the past two decades, substantial research has been conducted to investigate
      the idea that alterations in short-term nutritional intake play a role in
      influencing cognitive behaviour and mood. A portion of this research has examined
      specifically the effect of meal intake on the performance of mental tasks and
      subjective feelings of mood. Results of this research indicate that a number of
      variables including the timing and nutritional composition of the meal,
      nutritional status, habitual patterns of feeding behaviour, beliefs about food,
      and the nature of the mental tasks, can influence the effects of meals on
      cognitive behaviour. For example, studies have demonstrated that breakfast intake
      generally is associated with an improvement in cognitive performance later in the
      morning, while lunch intake is associated with an impairment in mid-afternoon
      performance on mental tasks and more negative reports of mood. Intake of
      nutrients late in the afternoon appears to have a positive effect on subsequent
      performance on tasks involving sustained attention or memory. Although research
      has provided insights into the role of meal intake on cognitive behaviour and
      mood, there are a number of factors which remain to be studied. These include the
      interaction of age, gender, activity level, meal composition, personality
      factors, stress with the effects of meals on cognitive behaviour. Additionally,
      more work is needed on the time-course of short-term nutrient effects, and the
      effects of chronic changes in meal intake on behaviour.

PMID- 9155500
TI  - The early days of the British Journal of Nutrition.

PMID- 9155499
TI  - Sugar, alternative sweeteners and meal frequency in relation to caries
      prevention: new perspectives.
AB  - In the last 20 years, mainly due to optimum fluoride exposure, and practice of
      good oral hygiene procedures, an important reduction in caries has been observed,
      despite the fact that sugar consumption was maintained and/or was increasing
      during the same lapse of time. A sugar-caries relationship cannot be established
      in most of the industrialized countries and the dietary factor is not as
      preponderant in the caries process as it used to be two decades ago. The factors
      which seem to contribute the most significantly to the cariogenicity of the diet
      are the frequency of carbohydrate ingestion and eating patterns. The relative
      cariogenicity of food is not correlated with the amount of carbohydrate it
      contains. Even if sucrose remains the most important sugar consumed in sweets,
      beverages and confectionery products, all fermentable-carbohydrate foods can be
      involved in the caries process. The use of chewing gum and other xylitol
      containing products have resulted in defined reduction in caries and represent
      interesting alternatives for high-caries-risk populations. Caries risk and oral
      health assessments as well as the evaluation of oral hygiene procedures and
      fluoride exposure should become essential tools in dietary counselling. People
      who receive optimum fluoride exposure and follow regular oral hygiene measures
      can safely use dietary carbohydrates, preferably during meals and two to three
      times daily in snacks or drinks.

PMID- 9155501
TI  - Energy intakes, anthropometry and body composition of Nigerian adolescent girls:
      a case study of an institutionalized secondary school in Ibadan.
AB  - Twenty-two apparently healthy Nigerian adolescent girls aged 11-17 years residing
      in a hostel, were studied over five consecutive days in order to assess their
      energy intake (EI), energy cost of specific activities and body composition (BC).
      The mean characteristics of the group were: height 1.58 (SD 0.1, range 1.42-1.68)
      m, body weight 49.1 (SD 7.9, range 34.0-61.0) kg and BMI 19.5 (SD 2.0, range 16.0
      23.0) kg/m2. The food intake of each subject was assessed by direct weighing and
      its energy value was determined by means of a ballistic bomb calorimeter. BMR
      values were calculated according to Food and Agriculture Organization/World
      Health Organization/United Nations University (FAO/WHO/UNU) (1985) equations.
      Percentage body fat (BF%) values were derived from three skinfold thickness
      measurements, using population-specific equations. The adolescents' mean daily EI
      was found to be 6510 (SD 855) kJ/d (138.3 (SD 27.8) kJ/kg body weight per d)
      which is lower than the FAO/WHO/UNU (1985) calculated energy requirement of 8800
      kJ/d for adolescent girls aged 12-14 years. The contributions of specific
      nutrients and individual meals to the total EI were: carbohydrate, protein and
      fat, 59.2, 12.5 and 28.3% of energy respectively and breakfast, lunch and supper,
      21.5, 41.0 and 37.4% respectively. However, the mean BMR was 5627 kJ/d, which is
      comparable with that given by FAO/WHO/UNU (1985) for adolescent girls aged 13-14
      years. The mean BF% was found to be 21.7. The comparatively low EI of the
      participants in the present study may be indicative of energy deficiency in their
      meals. This assumption is also reflected in their BC values. Nevertheless,
      further studies of this kind on adolescents in Nigeria are needed to confirm
      these observations.

PMID- 9155502
TI  - Acute effects of exercise on energy intake and feeding behaviour.
AB  - The main objective of the present study was to evaluate the short-term effects of
      exercise of different intensities on energy intake. Eleven young men were
      submitted to three randomly assigned sessions (one control and two exercise
      sessions) in which they ate, ad libitum, foods from a buffet-type meal. The
      energy cost of exercise was the same in the two exercise sessions. Results showed
      that there was no significant change in post-exercise subjective levels of hunger
      and fullness as well as total energy and macronutrient intakes in comparison with
      the control session. However, when energy intake relative to expenditure was
      considered by subtracting the surplus of energy expended during exercise from
      total energy intake, high-intensity exercise exerted a greater reducing effect on
      this variable compared with the control and low-intensity exercise sessions.
      These results suggest that for a given level of energy expenditure, high
      intensity exercise favours negative energy balance to a greater extent than low
      intensity exercise.

PMID- 9155503
TI  - Diurnal trends in responses of blood plasma concentrations of glucose, insulin,
      and C-peptide following high- and low-fat meals and their relation to fat
      metabolism in healthy middle-aged volunteers.
AB  - An experiment was conducted in twelve healthy middle-aged volunteers, six of each
      sex, with a mean BMI of 27 kg/m2 to detect differences between morning and
      afternoon in postprandial blood glucose, insulin and C-peptide concentrations.
      These responses were measured following the consumption of isoenergetic meals
      that were high or low in fat content, at breakfast and at lunch. Over 4 d each
      subject received the high-carbohydrate (L, 5.5 g mixed fat/meal) and moderately
      high-fat (M, 33 g mixed fat/meal) breakfasts and lunches, in three combinations
      (LL, MM, LM), or they fasted at breakfast time and received a moderately high-fat
      lunch (NM), in three Latin squares. Each evening a standard meal was given.
      Plasma glucose, insulin and C-peptide responses were greater following L than M
      meals and within both MM and LL treatments insulin and C-peptide responses were
      greater following breakfast than following lunch. The incremental C-peptide
      response to a fatty lunch following a fast at breakfast time (NM) was similar to
      that to a fatty breakfast, but the incremental insulin response for the same
      comparison was marginally lower at lunch (P = 0.06). The relationship of C
      peptide and insulin concentrations was assessed. Plasma glucose response to a
      fatty lunch was increased by a fatty breakfast. The relationships of these
      metabolic events with fat metabolism are discussed.

PMID- 9155504
TI  - Postprandial coagulation factor VII activity: the effect of monounsaturated fatty
      acids.
AB  - The present study investigated the effect of monounsaturated fatty acids (MUFA)
      on postprandial coagulation factor VII activity. Fifteen healthy male volunteers
      consumed three meals containing equal amounts (40 g) of fat, but providing
      different proportions of MUFA (12, 17 and 24% energy) in random order. Fasting
      and postprandial blood samples were drawn every hour for 9 h. The magnitude of
      the postprandial triacylglycerolaemic response and the postprandial plasma non
      esterified fatty acid (NEFA) concentrations were not significantly different
      following the three meals. Coagulation factor VII was activated during
      postprandial triacylglycerolaemia but the area under the curve of postprandial
      coagulation factor VII activity was not significantly different following the
      three meals. Regression analysis showed that fasting factor VII activity was the
      single most important factor affecting postprandial factor VII activity,
      irrespective of plasma lipid concentrations and meal fat composition. Peak
      postprandial factor VII activity was attained significantly earlier following the
      high-MUFA meal compared with the low-MUFA meal (6.33 (SD 2.16)h, 3.60 (SD 1.81)h
      respectively; P = 0.016). Regression analysis showed that meal MUFA content was
      the primary determinant of time to peak postprandial factor VII activity.
      Although the magnitude of postprandial coagulation factor VII activity was not
      affected by meal MUFA content, peak postprandial factor VII activity occurred
      earlier and fasting activity levels were quickly restored following the high-MUFA
      meal. A short-lived increase in factor VII activity may be more beneficial than a
      prolonged thrombotic response.

PMID- 9155505
TI  - Long-term supplementation with selenate and selenomethionine: urinary excretion
      by New Zealand women.
AB  - Thirty-six New Zealand women aged between 18 and 23 years received daily for 32
      weeks, 200 micrograms Se as Se-enriched yeast (selenomethionine, SeMet), or
      brewer's yeast mixed with selenate, or no added Se (placebo) in a double-blind
      trial. Mean daily Se excretion increased with both supplements; the selenate
      group excreted more than the SeMet group, 123 v. 66 micrograms/d respectively at
      week 2, equivalent to 57 v. 27% of the dose. Thereafter Se output increased for
      the SeMet group reaching a plateau at about 100 micrograms/d at week 16, when
      plasma Se had also plateaued at 190 ng/ml. The selenate group had reached an
      earlier plateau of 110 ng Se/ml at week 7. There was a close relationship between
      24 h urine and plasma Se for the SeMet group but not for the selenate group.
      Renal plasma clearances showed two distinctly different responses; the clearance
      of 0.4 ml/min reached by the SeMet group at week 2 plateaued as plasma Se
      increased almost 2-fold; whereas for the selenate group the clearance varied
      between 0.8 and 1.1 ml/min whilst plasma Se remained almost constant at 110
      ng/ml. Previous studies, also of 200 micrograms Se/d as Se-rich bread, in New
      Zealand (NZ) and elsewhere showed similar responses to Se-yeast; the selenite
      response was intermediate between selenate and Se-yeast (SeMet). The full
      significance of these studies awaits identification of Se components in plasma,
      glomerular filtrate and urine; meanwhile renal clearances serve as a pointer to
      changes in the distribution of Se-containing fractions in the plasma.
      Trimethylselenonium was detected in basal urines, and was a minor component in
      urines of supplemented NZ subjects at about 1% of the total Se.

PMID- 9155506
TI  - Protein utilization during energy undernutrition in sheep sustained by
      intragastric infusion: effects of protein infusion level, with or without sub
      maintenance amounts of energy from volatile fatty acids, on energy and protein
      metabolism.
AB  - Utilization of endogenous and exogenous energy for protein accretion during
      energy undernutrition has been studied. Nine lambs nourished by intragastric
      infusion were given either progressively increasing or decreasing amounts of
      casein-N up to 2550 mg/kg metabolic weight (W0.75), with or without 250 kJ/kg
      W0.75 of volatile fatty acids daily. Energy balance (respiration calorimetry) and
      N balance were measured. While all experimental animals were in negative energy
      balance, N balance increased curve-linearly with the increase in casein-N
      infusion and attained positive N balance. Endogenous energy (presumably body fat)
      was found to meet the energy needs for protein accretion during energy
      undernutrition. It is concluded that body fat can be effectively utilized to
      support lean-tissue growth during energy undernutrition, so that the classical
      nutritional concept of dietary energy:protein ratio is only meaningful when both
      endogenous and exogenous energy are considered.

PMID- 9155507
TI  - Excretion of benzoic acid derivatives in urine of sheep given intraruminal
      infusions of 3-phenylpropionic and cyclohexanecarboxylic acids.
AB  - The quantitative relationship between the urinary excretion of benzoic acid (BA)
      and the uptake of 3-phenylpropionic (PPA) and cyclohexanecarboxylic (CHCA) acids
      was assessed. PPA and CHCA are produced in the rumen by microbial fermentation of
      lignocellulosic feeds and metabolized, after absorption, to BA which is excreted
      in the urine mainly as its glycine conjugate hippuric acid (HA). Four sheep
      nourished by intragastric infusions of all nutrients were given continuous
      ruminal infusions of PPA (8, 16 or 24 mmol/d) either alone or with CHCA (8 or 16
      mmol/d) in a factorial experiment. The treatments were allocated to ten
      consecutive 6 d periods, with a control being repeated at periods 1, 5 and 10.
      PPA and CHCA ruminal absorption rates, estimated using the liquid-phase marker Cr
      EDTA, were 0.78 (SD 0.29)/h and 0.88 (SD 0.28)/h respectively. For the control,
      HA excretion was only 0.22 (SD 0.33) mmol/d and free BA was absent. For the other
      treatments, both HA and free BA were present and HA accounted for 0.85 (SD 0.05)
      of total BA: The urinary excretion of total BA showed a significant linear
      correlation (r = 0.997, P < 0.001) with the amounts of PPA and CHCA infused. The
      urinary recovery of infused PPA and CHCA as total BA was 0.79 (SE 0.01). Faecal
      excretion of BA and its precursors was negligible. Results of this study show
      that urinary total BA is a potential estimator of the absorption of PPA + CHCA
      produced in the rumen.

PMID- 9155508
TI  - Tissue localization of threonine oxidation in pigs.
AB  - Two experiments were designed to determine the tissue distribution of threonine
      oxidation through the threonine dehydrogenase (EC 1.1.1.103) pathway in pigs. The
      first experiment was conducted on eleven Pietrain x Large White piglets. The
      piglets were slaughtered at 5, 12 or 20 kg after 1 h of infusion with L-[U
      14C]threonine (55 kBq/kg) mixed with unlabelled threonine (100 mg/kg). In the
      second experiment, four Pietrain x Large White and four large White piglets (10
      kg body weight) were infused with L-[1-13C]threonine (50 mg/kg) mixed with 50
      mg/kg unlabelled threonine for 1 h, then killed for tissue sampling. In the two
      experiments, threonine dehydrogenase specific activity and threonine and glycine
      specific radioactivities and enrichments were measured in several tissues and in
      plasma. The higher level of labelling of threonine in the pancreas than in the
      liver suggested either a lower protein degradation rate or a faster rate of
      threonine transport in the liver than in the pancreas. Threonine dehydrogenase
      activity was found only in the liver and the pancreas. Whereas liver and pancreas
      threonine dehydrogenase specific activities were similar, glycine specific
      radioactivity and enrichment were 12- to 14-fold higher in the pancreas than in
      the liver. This is probably the consequence of a higher production rate of
      glycine from sources other than threonine (protein degradation, de novo synthesis
      from serine) in the liver than in the pancreas. Our results showed that Large
      White pigs could oxidize more threonine than Pietrain x Large White pigs. This
      could be related to the difference in growth performance and dietary N efficiency
      for protein deposition between these two genotypes.

PMID- 9155509
TI  - Effect of dietary fats rich in lauric, myristic, palmitic, oleic or linoleic acid
      on plasma, hepatic and biliary lipids in cholesterol-fed hamsters.
AB  - Effects of different dietary fats on plasma, hepatic and biliary lipids were
      determined in male golden Syrian hamsters (Mesocricetus auratus) fed on purified
      diets for 7 weeks. Diets were made by blending different fats containing
      characteristic fatty acids: butter (14:0 + 16:0), palm stearin (16:0), coconut
      oil (12:0 + 14:0), rapeseed oil (18:1), olive oil (18:1) and sunflowerseed oil
      (18:2). In all diets except the sunflowerseed oil diet dietary 18:2 was held
      constant at 2% energy. Total fat supplied 12% of energy and cholesterol was added
      at 4 g/kg diet. Plasma cholesterol and triacyglycerol concentrations were
      increased by dietary cholesterol. After 7 weeks, plasma cholesterol
      concentrations were highest with the palm stearin, coconut oil and olive oil
      diets (8.9, 8.9 and 9.2 mmol/l) and lowest with the rapeseed oil and
      sunflowerseed oil diets (6.7 and 5.5 mmol/l) while the butter diet was
      intermediate (8.5 mmol/l). Hepatic cholesterol concentration was highest in
      hamsters fed on the olive oil diet and lowest with the palm stearin diet (228 v.
      144 mumol/g liver). Biliary lipids, lithogenic index and bile acid profile of the
      gall-bladder bile did not differ significantly among the six diets. Although the
      gallstone incidence was generally low in this study, three out of 10 hamsters fed
      on the palm stearin diet developed cholesterol gallstones. In contrast, no
      cholesterol gallstones were found with the other diets. Rapeseed and
      sunflowerseed oils caused the lowest plasma cholesterol and triacyglycerol
      concentrations whereas olive oil failed to demonstrate a cholesterol-lowering
      effect compared with diets rich in saturated fatty acids. Since 18:2 was kept
      constant at 2% of energy in all diets, the different responses to rapeseed and
      olive oils could possibly be attributed to their different contents of 16:0 (5.6%
      v. 12.8% respectively). Other possible explanations are discussed.

PMID- 9155510
TI  - The effects of feeding suet-enriched chow on site-specific differences in the
      composition of triacylglycerol fatty acids in adipose tissue and its interactions
      in vitro with lymphoid cells.
AB  - The effects of diet on the composition and properties of adipose tissue in
      relation to lymph nodes were studied in adult guinea-pigs. The proportions of
      monoenoic triacylglycerol fatty acids were constant in all sites in adipose
      tissue of similarly fed guinea-pigs, but were substantially greater in samples
      from guinea-pigs fed on suet-enriched chow. Triacylglycerols in adipose tissue
      from near nodes contained significantly fewer saturated fatty acids, and
      significantly more 18:2n-6 and 18:3n-3 than those in samples from sites remote
      from nodes within the same depot. Depots that interact most strongly with
      lymphoid cells in vitro had the largest and most consistent within-depot
      differences. The gradients of triacylglycerol fatty acid composition with
      distance from lymph nodes in two small intermuscular depots were similar in
      guinea-pigs fed on plain or suet-enriched chow. These findings are consistent
      with the hypothesis that adipose tissue around lymph nodes is specialized for
      local interactions with the lymphoid cells therein, and help to explain the
      variability of serial or duplicate measurements of adipose tissue composition.
      When cultured alone, lipopolysaccharide-stimulated lymph node lymphoid cells from
      suet-fed guinea-pigs incorporated as much labelled thymidine as the controls.
      Adipose tissue explants from suet-fed guinea-pigs inhibited lymphocyte
      proliferation much less than those of the controls, although the site-specific
      differences were similar. The pattern of site-specific differences in glycerol
      released from explants incubated alone was generally similar for both dietary
      groups, but except in the popliteal depot, the increases following co-culturing
      with lymphoid cells were smaller for samples from suet-fed guinea-pigs. These
      experiments show that minor changes in the fatty acid composition of the diet can
      substantially alter the interactions between adipose tissue and lymphoid cells.

PMID- 9155511
TI  - Linoleic and alpha-linolenic acids differently modify the effects of elaidic acid
      on polyunsaturated fatty acid metabolism and some immune indices in rats.
AB  - To explore whether the metabolic responses to trans, compared with cis, fatty
      acids depend on the source of dietary polyunsaturated fatty acids (PUFA), male
      Sprague-Dawley rats, 5 weeks old, were fed on diets containing 30 g oleic (cis)
      or elaidic (trans) acids/kg in combination with either 70 g perilla oil (alpha
      linolenic acid) or safflowerseed oil (linoleic acid)/kg for 3 weeks in separate
      experiments. The dietary fats were adjusted to have the same level of total PUFA.
      The dietary manipulation did not influence the growth indices, but spleen weight
      was greater when the dietary PUFA source was perilla oil. The incorporation of
      trans fatty acid into liver phosphatidylcholine, phosphatidylethanolamine,
      phosphatidylinositol and phosphatidylserine and adipose tissue lipids,
      particularly phospholipids, was significantly higher when rats were fed on
      safflowerseed oil compared with perilla oil. However, only limited differences
      were observed in the effects of cis and trans fatty acids on the proportions of
      PUFA in liver phospholipids. Splenic production of prostaglandin E2 was reduced
      by trans fatty acid when safflowerseed oil was the PUFA source, but no trans
      effect was observed on leukotriene C4 production. Dietary PUFA significantly
      influenced the concentration of plasma immunoglobulins (Ig) but the effect of
      geometry was only seen in IgG which was increased by trans acid. Dietary trans
      fatty acid increased the CD4+:CD8+ T-lymphocyte ratio in the spleen, reflecting a
      decreasing trend of the proportion of CD8+, when combined with perilla oil. These
      observations indicate that the type of PUFA simultaneously ingested specifically
      influences the effect that trans acid exerts on PUFA metabolism, eicosanoid
      production and some immune indices.

PMID- 9155512
TI  - Dietary fat affects lipids and anti-cardiolipin antibody levels in autoimmune
      prone NZB/W F1 mice.
AB  - Studies in autoimmune-prone NZB/W F1 mice have demonstrated that the amount of
      dietary fat can affect autoantibody production and the disease course of
      autoimmune diseases. Anti-cardiolipin antibodies have been found to play a major
      role in thrombus formation and the increase of abortion rate in both human lupus
      patients and murine lupus. The present study investigated further the effect of
      dietary fat on lipid and anti-cardiolipin antibody production in autoimmune-prone
      mice. Two groups of NZB/W F1 mice were fed on diets containing 200 g dietary
      fat/kg and 50 g dietary fat/kg respectively, the fat being composed of equal
      amounts of lard and soyabean oil. Serum levels of lipids, immunoglobulin (Ig)
      anti-single stranded DNA and anti-cardiolipin antibodies were followed regularly
      every month and mice were killed for in vitro experiments after 5 months on the
      experimental diets. The results showed that serum triacylglycerol concentration
      was lower in mice fed on the high-fat diet than in those fed on 50 g fat/kg.
      There was no significant difference in hepatic lipid contents; however, the fatty
      acid contents were different between these two groups. Hepatic linoleic acid
      (18:2n-6) and arachidonic acid (20:4n-6) concentrations were higher in mice fed
      on the high-fat diet. There were no significant differences in serum IgM
      concentrations or IgM anti-cardiolipin antibody levels between these two groups.
      However, IgG anti-cardiolipin antibody levels were higher in mice fed on the high
      fat diet at the age of 3-4 months. Total serum IgG concentration was noted to be
      higher, but in contrast, serum IgA was lower, in the high-dietary-fat group.
      These findings suggest that high dietary fat may affect lipid metabolism and
      autoantibody levels in autoimmune diseases.

PMID- 9155513
TI  - Prostate cancer, populations, politicians and power.

PMID- 9155514
TI  - Recent developments in the epidemiology of prostate cancer.
AB  - The purpose of this review is to examine the implications of recent trends in
      prostate cancer incidence and mortality and to consider recent progress of
      epidemiological research on this disease. The incidence and mortality rates for
      prostate cancer are changing throughout the world at an accelerating pace. Much
      of the increase in incidence is related to changes in detection technology, but
      increases in mortality rates suggest other factors are involved. Recent research
      has focused on race-related difference, diet and related lifestyle exposures, the
      aetiologic significance of vasectomy and, patterns of familial aggregation.
      Continued monitoring of trends in incidence and mortality will be important as
      prostate cancer becomes a greater public health burden worldwide. Epidemiological
      research has identified several possible risk factors which may be useful for
      prostate cancer prevention and targeting high-risk individuals for early
      detection intervention. Additional research may confirm and refine understanding
      of prostate cancer aetiology.

PMID- 9155515
TI  - Is screening for prostate cancer the current gold standard?--"no".

PMID- 9155516
TI  - Is screening for prostate cancer the current gold standard?--"yes".

PMID- 9155517
TI  - The outcome of advanced soft tissue sarcoma patients with complete tumour
      regression after either chemotherapy alone or chemotherapy plus surgery. The
      Scandinavian Sarcoma Group experience.
AB  - The intensified induction regimens used and the potential use of high-dose
      consolidation chemotherapy (CT) in advanced soft tissue sarcomas (STS) has
      focused interest on the outcome of those patients who can achieve complete
      remission (CR) by current therapy. The files from four institutions with a
      special interest in STS were studied. 38 adult patients with advanced STS who
      were converted disease-free by either CT alone (n = 14) or CT followed by surgery
      (n = 24) were found. The median follow-up time was 29 months. The median disease
      free survival (DFS) was 18 months and the estimated 2-year DFS 34%. The median
      disease-specific survival (DSS) was 40 months and the estimated 2-year DSS 78%.
      For patients who achieved CR by CT alone, and for patients who were converted to
      CR by surgery, the corresponding DFS figures were 23 months (estimated 2 year DFS
      48%) and 10 months (26%) (P = 0.07), respectively. The histological response to
      CT significantly predicted outcome in patients subjected to surgery (DFS P value
      0.004, DSS P value 0.02). Patients who achieved CR by surgery shortly after
      having achieved a clinical partial response (PR with early surgery) did better
      than those who where converted to CR by surgery after protracted CT following a
      clinical PR (PR with late surgery) (DFS P value 0.02, DSS P value 0.1). Our
      results confirm that CT alone can induce prolonged DFS in rare patients with
      advanced STS. In patients subjected to surgery, a good histological response
      indicates improved outcome.

PMID- 9155518
TI  - Tumour biological features of BRCA1-induced breast and ovarian cancer.
AB  - BRCA1 mutations, although implicated in disease predisposition in a major part of
      the hereditary breast cancer population, do not seem to be crucially involved in
      tumorigenesis of sporadic breast and ovarian cancers. This suggests that tumours
      arising in BRCA1 mutation carriers may differ from BRCA1 negative hereditary and
      sporadic cancer in genetic and biological features, as well as in clinical
      behaviour. Prior to BRCA1 analysis, 79 breast and 19 ovarian tumours from 57
      breast and breast-ovarian cancer families, and 170 tumours from a comparison
      group of stage II breast cancers were studied with regard to histopathological
      features; immunohistochemistry [c-erbB-2, p53, oestrogen receptor (ER) and
      progesterone receptor (PR)], DNA flow cytometry and S-phase fraction. BRCA1
      mutations were found in 40 breast and 15 ovarian tumours. The BRCA1 positive
      breast tumours were significantly more often of ductal type, histological grade
      III and manifested a heavy lymphocyte infiltration. Additionally, as compared to
      BRCA1 negative tumours, the BRCA1 positive tumours were significantly more often
      ER, PgR and c-erbB-2 negative. Furthermore, they were significantly more often
      DNA non-diploid, as well as being characterised by higher S-phase fraction
      values. These results suggest that BRCA1-induced breast cancers may manifest
      distinct tumour biological features of clinical importance.

PMID- 9155520
TI  - Extended phase II study of paclitaxel as a 3-h infusion in patients with ovarian
      cancer previously treated with plantinum.
AB  - An extended phase II study was performed to evaluate single-agent paclitaxel as
      salvage chemotherapy for ovarian cancer. The aim of this study was to evaluate
      the 3-h infusion schedule of paclitaxel in terms of toxicity and antitumour
      efficacy. Furthermore, we analysed the impact on response and survival of the
      extent of prior chemotherapy and status of resistance against platinum. This
      study was an open, non-randomised, multicentre trial. The dose of paclitaxel used
      was 175 mg/m2 in patients who had received one or two prior therapies, and 135
      mg/m2 in patients who had received three prior therapies. Paclitaxel was given as
      a 3-h infusion. Courses were repeated every 3 weeks. 114 patients with platinum
      pretreated epithelial ovarian cancer were recruited of whom 112 were found
      eligible and evaluable for toxicity. 104 patients with bidimensionally measurable
      disease who received more than one course of chemotherapy were evaluable for
      response, progression-free (PFS) and survival. Toxicity was generally manageable.
      Main toxicities were non-cumulative neutropenia with 22.3% of courses with WHO
      grade 3/4 and peripheral neuropathy which occurred in more than half of the
      courses and was of WHO grade 2 and 3 in 20.1 and 1.3% of the courses,
      respectively. Neuropathy was associated with the higher dose per course and with
      cumulative paclitaxel dose. Objective responses were reported in 20% (21/104) of
      the patients (95% CI 13-29%) with a median response duration of 36.7 weeks.
      Survival and PFS for the whole group were 45.9 and 15.1 weeks, respectively.
      Performance status, number of tumour lesions and extent of prior chemotherapy
      were found to be prognostic factors for survival. Extent of prior chemotherapy
      was the only prognostic factor for PFS. Platinum resistance did not predict
      response to treatment. Paclitaxel 175 mg/m2 given as a 3-h infusion is an
      appropriate treatment for patients with platinum-resistant ovarian cancer who
      have not previously received more than two chemotherapy regimens. Paclitaxel did
      not show results superior to historical data for platinum retreatment in patients
      with platinum-sensitive, recurrent ovarian cancer.

PMID- 9155519
TI  - Tandem high-dose therapy with ifosfamide, epirubicin, carboplatin and peripheral
      blood stem cell support is an effective adjuvant treatment for high-risk primary
      breast cancer.
AB  - We evaluated the therapeutic efficacy and toxicity of a tandem high-dose therapy
      with peripheral blood stem cell (PBSC) support in 40 patients with high-risk,
      primary breast cancer (stage II-III) and involvement of ten or more positive
      axillary lymph nodes. Their median age was 44 years (range 23-56). Two cycles of
      cytotoxic chemotherapy with ifosfamide (10000 mg/m2) and epirubicin (100 mg/m2)
      were administered. Granulocyte colony-stimulating factor (G-CSF) was given to
      hasten neutrophil reconstitution and to mobilise PBSC during marrow recovery.
      Leukaphereses were performed following the first and/or second cycle. Tandem high
      dose therapy consisted of two cycles with ifosfamide (15 or 12 g/m2) and
      epirubicin (150 mg/m2), while carboplatin (900 mg/m2) was added for the last 24
      patients included. Using an immunocytochemical method, two of 11 patients had
      cytokeratin-positive tumour cells in three leukapheresis products that were
      collected following the first G-CSF-supported cycle with ifosfamide and
      epirubicin, whereas only two harvests obtained following the second cycle in 26
      patients contained cytokeratin-positive tumour cells. The number of CD34+
      cells/kg re-infused following both high-dose cycles was similar (4.20 +/- 0.29 x
      10(6), first cycle and 5.25 +/- 0.63 x 10(6), second cycle), and no notable
      difference was noted in the speed of haematological reconstitution. An absolute
      neutrophil count (ANC) of 0.5 x 10(9)/1 was reached after a median time of 13
      days, while an unsupported platelet count of 20.0 x 10(9)/1 was achieved after a
      median time of 8 (first cycle) and 9 (second cycle) days post-transplantation.
      Patients autografted with more than 7.5 x 10(6) CD34+ cells/kg had platelet
      counts above 20 x 10(9)/1 within less than 10 days. 6 patients relapsed between 7
      and 11 months (median 8 months) post-transplantation. 37 patients are alive and
      in remission with a median follow-up time of 11 months (range 1-38). This
      translates into a probability of disease-free survival (DFS) of 77% (95% CI 32
      95%) at 38 months. The probability of overall survival is 85%, since 3 patients
      with local relapse achieved a second complete remission following surgery and
      involved-field radiotherapy. In conclusion, a sequential high-dose therapy
      including ifosfamide, epirubicin, carboplatin and PBSC support is well tolerated
      and effective in patients with high-risk primary breast cancer. Involved-field
      irradiation should be performed post-transplantation to reduce the risk of local
      relapse.

PMID- 9155521
TI  - Diagnostic and prognostic value of Cyfra 21-1 compared with other tumour markers
      in patients with non-small cell lung cancer: a prospective study of 116 patients.
AB  - The diagnostic value of Cyfra 21-1 in non-small lung cancer (NSCLC) has been
      established, but few studies have focused on its prognostic value. The aim of
      this study was to compare that of carcinoembryonic antigen (CEA), carbohydrate
      antigen (CA) 19-9, CA 125, neuron-specific enolase and squamous cell carcinoma
      antigen. 116 patients with unresectable (n = 88) or resectable (n = 28) NSCLC
      were prospectively monitored from diagnosis, for a median of 14.4 months. All
      patients underwent tumour-marker determinations before treatment, then every 3
      months. Their diagnostic value was studied using ROC (receiver operating
      characteristic) curves, based on control measure in 23 patients with benign lung
      diseases. The prognostic analysis was based on overall survival as the main
      endpoint. The diagnostic value of Cyfra 21-1 was confirmed, with a sensitivity of
      54% and a specificity of 96% at a cut-off value of 3.3 ng/ml. At diagnosis, in
      the 88 non-surgical NSCLC, besides the presence of metastases (P = 0.017), Cyfra
      21-1 (P = 0.017) and CA 125 (P = 0.03) were related to outcome. Elevated levels
      of Cyfra 21-1 at any time during the disease course was selected by multivariate
      analysis as additional predictors of poor survival.

PMID- 9155522
TI  - Vinorelbine is well tolerated and active in the treatment of elderly patients
      with advanced non-small cell lung cancer. A two-stage phase II study.
AB  - More than 30% of lung cancers arise in patients aged 70 years or more; however,
      because elderly patients are not considered to tolerate chemotherapy, they are
      generally excluded from clinical trials and are not considered eligible for
      aggressive cisplatin-based chemotherapy in clinical practice. The aims of the
      present study were to test tolerability and activity of weekly vinorelbine in
      advanced non-small cell lung cancer (NSCLC) patients aged 70 years or more, and
      to define whether minimum conditions existed for a randomised comparison with
      best supportive care. The study was designed as a multicentre two-stage phase II
      trial according to Simon's optimal design: 8 or more responses out of 43 treated
      patients were expected at the end of the trial. Patients aged 70 years or more
      were eligible if they had a cytological or histological diagnosis of NSCLC at
      stage IIIb-IV and a performance status less than or equal to two according to the
      ECOG scale. Vinorelbine was given intravenously (i.v.) at a dose of 30 mg/m2
      every week for 12 doses. As planned, 43 patients entered the study; median age
      was 73 years (range 70-80); 11 patients were older than 75 years. Median dose
      intensity (mg/m2/week) of vinorelbine was 21.2 (range 7.5-30) and was not
      affected by age of patients. Toxicity was generally mild, mainly haematological
      and never life-threatening. ECOG performance status improved in 26% of patients;
      cough and pain improved in more than 40% of patients symptomatic at entry, while
      dyspnoea improved in 28%; approximately half the patients had a stabilisation of
      their symptoms. 10 patients (23-95% exact confidence interval (CI): 12-39%)
      obtained a partial response. Median time to progression was 11 weeks (95% CI 8
      30) and median survival 36 weeks (95% CI 28-53). One-year estimated progression
      free and overall survival rates are 16% and 36%, respectively. In conclusion,
      vinorelbine was well tolerated and active in the treatment of elderly NSCLC
      patients. A phase III trial (ELVIS-Elderly Lung Cancer Vinorelbine Italian Study)
      comparing best supportive care versus best supportive care plus vinorelbine is
      now ongoing.

PMID- 9155523
TI  - A prospective analysis of 949 long-term central venous access catheters for
      ambulatory chemotherapy in patients with gastrointestinal malignancy.
AB  - We present a prospective analysis of the insertion complications and longevity of
      949 cuffed, tunnelled central venous catheters used for ambulatory chemotherapy.
      Mean catheter life span was 121.8 days, 13.4% had complications at insertion,
      17.7% had complications not necessitating removal and 18.6% had complications
      requiring removal. The more experienced operators had fewer complications
      inserting catheters (P < 0.0001). Late-onset shoulder pain occurred in 4.8% and
      was associated with an increased incidence of venous thrombosis (P < 0.0001) and
      infection (P = 0.06). Complications necessitating removal were not predicted by
      patient' age, site of insertion or malignancy, chemotherapy regimen, insertion
      platelet and fibrinogen counts, insertion complications, leucocyte count or cuff
      distance from the exist site. Catheters inserted with their tip in the superior
      vena cava were more at risk of removal (2.57 times) than those in the right
      atrium (P = 0.003).

PMID- 9155524
TI  - Assay of E-cadherin by ELISA in human breast cancers.
AB  - E-cadherin is a membrane-bound adhesion glycoprotein. Loss of E-cadherin has been
      correlated with invasion and metastasis in model systems. Using a new ELISA, we
      found higher levels of E-cadherin in fibroadenomas than in primary breast
      cancers. Levels in primary cancers showed no significant relationship with either
      tumour size, nodal status or oestrogen receptor levels. Patients with breast
      cancers containing low levels of the adhesion protein had a significantly shorter
      disease-free interval than patients with high levels (P = 0.041). The prognostic
      value of E-cadherin, for disease-free interval, was also found in node-negative
      patients as well as in patients presenting with small tumors (< or = 2 cm). In
      conclusion, loss of E-cadherin expression in human breast cancers is associated
      with increased metastatic potential as has previously been found in model
      systems. Loss of E-cadherin is thus likely to contribute to breast cancer
      progression.

PMID- 9155525
TI  - Wilms' tumour.

PMID- 9155526
TI  - The effect of the neuroblastoma-seeking agent meta-iodobenzylguanidine (MIBG) on
      NADH-driven superoxide formation and NADH-driven lipid peroxidation in beef heart
      submitochondrial particles.
AB  - In this paper we report the effects of the neuroblastoma-seeking agent meta
      iodobenzylguanidine (MIBG) on NADH-driven superoxide formation and NADH-driven
      lipid peroxidation in beef heart submitochondrial particles. MIBG is a structural
      analogue of noradrenaline and is capable of inhibiting complex I and complex III
      of the respiratory chain. The results of our studies show that MIBG enhanced both
      NADH-driven superoxide formation and NADH-driven lipid peroxidation at
      concentrations that are likely to exist inside mitochondria of the target cells
      of neuroblastoma patients treated with [131I]MIBG. The effect of MIBG is
      comparable to that of rotenone (an inhibitor of complex I) rather than that of
      antimycin (an inhibitor of complex III). These results suggest that the formation
      of superoxide and lipid peroxidation contributes to the cytotoxicity of
      [131I]MIBG.

PMID- 9155527
TI  - Effect of age on the survival of breast cancer patients.
AB  - Despite numerous studies, the effect of patient age on the prognosis of breast
      cancer is still uncertain. The aim of this study was to assess the influence of
      age on long-term relative survival, to control the results for the extent of
      disease at diagnosis and assess the association between biological markers and
      age of the patients. A population-based survival study was made to assess the 5-
      and 10-year relative survival. All 17,856 female breast cancer patients diagnosed
      in Finland and reported to the Finnish Cancer Registry in 1977-1986 were
      included. The results were controlled for the extent of the disease. The markers
      of biological aggressiveness of tumours and patients' age were correlated in a
      prospectively collected subset of 2107 patients from the Tampere University area.
      The relative 5-year and 10-year survival rates (RSRs) were highest in women 46-50
      years of age, whereas there was no significant difference between younger and
      older age groups. No consistent survival trends were observed among the age
      groups in local, node-negative disease, whereas in node-positive disease the 10
      year relative survival was best for women 41-45 years (49%) and poorest in women
      over 75 years (35%). The youngest age groups were significantly more often
      oestrogen receptor-negative, but only small differences were observed for S-phase
      fraction and progesterone receptor positivity.

PMID- 9155528
TI  - A comparison of the performance and impact of breast cancer screening programmes
      in East Anglia, U.K. and Bouches du Rhone, France.
AB  - The purpose of this study was to compare results from the first screening round
      of two breast cancer screening programmes of similar design implemented in
      different health care settings. The East Anglian programme is part of the U.K.
      National Health Service Breast Screening Programme, which is a centralised
      programme with a limited number of dedicated screening units. The Bouches du
      Rhone programme is one of 13 French programmes based on a decentralised model
      using existing radiology clinics. Compliance and cancer detection rates were
      lower in the Bouches du Rhone programme. Detection rates for small invasive
      cancers (< or = 10 mm) were similar in the two programmes, although larger
      cancers (> or = 20 mm) were detected in the Bouches du Rhone programme.
      Significantly, the shift towards more favourable distribution of prognostic
      characteristics associated with screen-detected breast cancers compared with
      those arising outside the programme is less marked in the Bouches du Rhone
      programme. This is probably due to the more favourable underlying disease status
      in the district resulting from a long history of breast awareness and spontaneous
      mammography.

PMID- 9155529
TI  - Improved survival of Hodgkin's patients in south-east Netherlands since 1972.
AB  - In the past 30 years, staging and treatment of Hodgkin's disease have changed
      dramatically, and prolonged remission can now be induced in the majority of
      patients. Our purpose was to assess improvement in long-term survival, previously
      reported for specific patient groups, among unselected patients diagnosed and
      treated between 1972 and 1993 in general hospitals in South-East Netherlands.
      Data on all 345 Hodgkin's patients were derived from the population-based
      Eindhoven Cancer Registry; histopathology and clinical records were reviewed.
      Follow-up was attained up to 1994. Relative survival rates, i.e. the ratio of
      observed to expected rates, were 80% after 5, 70% after 10 and 67% after 15
      years. Independent prognostic factors for lower overall survival were (in
      decreasing order of significance): advanced age, histology (lymphocyte
      depletion), advanced stage and earlier period of diagnosis. Distribution of age
      and stage did not change over the study period, but there was a modest increase
      in the incidence of the nodular sclerosis histological subtype. Crude 5-year
      survival rates improved from 60% in the period 1972-1976 to 81% in the period of
      1987-1992 (P < 0.005). The largest improvement occurred in the 1970s and was most
      prominent among those aged over 50 years. As previously reported, cured Hodgkin's
      patients exhibit a higher mortality rate, which can be explained by treatment
      related long-term complications such as second malignancies and cardiovascular
      diseases. The relatively high survival rates compared to other population-based
      studies may be attributable to the existence of a regional network within the
      framework of a comprehensive cancer centre. Better staging, new combinations of
      chemotherapy, improved radiation technology, advances in supportive care as well
      as more frequent intensive treatment of the elderly could explain the improvement
      in prognosis.

PMID- 9155530
TI  - D-21266, a new heterocyclic alkylphospholipid with antitumour activity.
AB  - The aim of this study was to determine the antitumour effects of D-21266 in a
      rodent tumour model. Hexadecylphosphocholine (INN: Miltefosine) represents the
      first anticancer agent which was specifically formulated for topical use in
      cancer patients. The development as an oral drug was hampered by the
      gastrointestinal toxicity. Hexadecylphosphocholine derivatives were sought with a
      better therapeutic index. Octadecyl-(1,1-dimethyl-4-piperidylio) phosphate (D
      21266) was identified as a suitable candidate. This compound is highly active in
      vitro inhibiting the growth of a number of human cancer cell lines. Mammary
      carcinomas were induced in Sprague-Dawley rats using DMBA, and oral doses of D
      21266, in various schedules, were given to the animals. A high antineoplastic
      potency was observed without inducing loss of body weight at highly effective
      doses. The antitumour effect could be enhanced by introducing a dose schedule
      consisting of a high loading dose followed by a low maintenance dose, both of
      which are only marginally active when given alone. Therefore, D-21266 with its
      favourable pharmacological and toxicological profile, warrants evaluation in the
      clinic. However, the concept of clinical trials requires new approaches to dose
      finding and response evaluation, because the dose-response relationship of this
      compound is distinctly different from that of classical cytostatic agents.

PMID- 9155531
TI  - Role of O6-methylguanine-DNA methyltransferase, glutathione transferase M3-3 and
      glutathione in resistance to carmustine in a human non-small cell lung cancer
      cell line.
AB  - O6-methylguanine-DNA methyltransferase (MGMT), glutathione transferase (GST) M3-3
      and glutathione (GSH) have all been implicated in the resistance of cells to the
      cytostatic drug carmustine. U1810, a human non-small cell lung cancer cell line,
      expresses all of these putative resistance factors. The U1810 cells show a 4.4
      fold lower sensitivity to carmustine compared with the U1690 cell line, a human
      small cell lung cancer cell line lacking detectable levels of both MGMT and GST
      M3-3. We investigated the effect of the MGMT inhibitor O6-benzylguanine, the GST
      inhibitor ethacrynic acid and the GSH synthesis inhibitor D,L-buthionine-S,R
      sulfoximine (BSO) on the cytotoxicity of carmustine to U1810 cells. No
      potentiation to carmustine was observed after treatment with ethacrynic acid,
      while a 2-fold potentiation was found after exposure to O6-benzylguanine.
      Depletion of GSH with BSO showed a similar sensitising effect as that obtained
      with O6-benzylguanine. Thus, MGMT and GSH are the predominant resistance factors
      to carmustine in the U1810 cell line, whereas it is unclear whether GST M3-3
      plays any role.

PMID- 9155532
TI  - Determination of radiosensitivity in established and primary squamous cell
      carcinoma cultures using the micronucleus assay.
AB  - In this study, the cytokinesis-block micronucleus assay (CBMN) was used to
      measure radiosensitivity in three established cell lines (SCC-61, V175 and V134)
      and 10 primary cell cultures of squamous cell carcinoma (SCC) of the head and
      neck. Assessment involved optimisation of the assay to determine cytochalasin-B
      (CB) concentration and sampling time postirradiation. A much closer correlation
      between dose-response data measured in the clonogenic and micronucleus assays was
      found when the micronucleus assay was performed under standardised conditions for
      each cell line (2 micrograms/ml CB: 48 h postirradiation) instead of
      predetermined optimised assay conditions. This indicates that, for these SCC cell
      lines, the CBMN assay may be able to predict in vitro radiosensitivity. To be of
      clinical use in predicting radiosensitivity, the CBMN assay also needs to be
      evaluated with primary cell cultures. In this study, no relationship between
      micronucleus frequency at 2 or 6 Gy and patient clinical outcome 12 months
      following surgery and radiotherapy was seen. Similarly, no association between
      patient outcome and tumour stage, nodal stage and histology was observed. These
      CBMN assay data from the primary cell cultures are presently inconclusive as a
      measure of patient tumour radiosensitivity.

PMID- 9155533
TI  - In vitro synergy of paclitaxel (Taxol) and vinorelbine (navelbine) against human
      melanoma cell lines.
AB  - Paclitaxel (PTXL) (Taxol), a taxane, and vinorelbine (VRB), a semisynthetic vinca
      alkaloid drug, have tubulin as their common intracellular target, but inhibit
      growth by binding to different sites. We evaluated in vitro the antiproliferative
      activity of these two drugs as single agents and in combination, against two
      human melanoma cell lines, G361 and StM111a. The SRB (sulphorhodamine B) assay
      was used to determine growth inhibition. Possible drug-drug interaction at the
      cellular level was assessed by constructing Isoboles (Isobologram analysis) and
      applying the concept of an 'envelope of additivity'. Both agents were active in
      the nanomolar range at clinically achievable concentrations. The mean IC50 for
      G361 was 46.6 nM (PTXL) and 19.9 nM (VRB) after a 1 h drug exposure. Mean IC50 (1
      h) for StM111a was 9.7 nM (PTXL) and 26.9 nM (VRB). Isobole analysis at the
      isoeffect levels of 25%, 50% and 75% indicated that drug interaction was
      predominantly synergistic (supra-additive) when paclitaxel and VRB were added
      concurrently for 1 h to cultures of StM11 1a or G361. In some experiments, this
      synergy was observed with particularly low concentrations of paclitaxel (3 nM)
      and VRB (0.01 nM). A new points were located within the envelope of additivity or
      in the subadditive (antagonism) region of the isobole. An overall synergy was
      also found if the data were analysed by the median effect analysis. The effect of
      these agents on the cytoskeleton and ultrastructure were studied with
      immunofluorescence and electron microscopy, respectively. These results confirm
      the in vitro inhibitory activity of paclitaxel and VRB against malignant
      melanoma, but more importantly the two drugs appear to act synergistically at
      relatively low concentrations.

PMID- 9155534
TI  - Biochemical mechanisms of interferon modulation of 5-fluorouracil activity in
      colon cancer cells.
AB  - The antiproliferative effect of 5-fluorouracil (5-FU) in colon cancer can be
      enhanced by interferons (IFN-alpha and IFN-gamma). The mechanisms by which IFNs
      modulate 5-FU activity are not completely elucidated. IFN-alpha may elevate the
      levels of the active 5-FU metabolite 5-fluoro-2'-deoxyuridine-5'-monophosphate
      (FdUMP) in the cell, possibly leading to increased inhibition of the target
      enzyme thymidylate synthase (TS), which might enhance DNA damage. It has been
      shown that IFN-gamma can prevent 5-FU induced overexpression of TS. We studied
      IFN modulation in three colon cancer cell lines (SW948, WiDr, human; C26-10,
      murine) and the sublines WiDr/F and C26-10/F, which were adapted to low folate
      levels. A 1.5-fold increase in 5-FU sensitivity was observed in C26-10 and C26
      10/F (by murine IFN-alpha, beta); in SW948, WiDr and WiDr/F (by human IFN-gamma)
      and in SW948 and WiDr/ F (by human IFN-alpha). In none of the cell lines did
      human IFN-alpha, IFN-gamma or murine IFN-alpha, beta increase FdUMP levels after
      exposure to 5-FU. TS activity, indirectly measured by incorporation of [6-3H]
      deoxyuridine into DNA, was inhibited by 5-FU, but the IFNs did not enhance
      inhibition. DNA damage was measured as a drug-induced decrease of double-stranded
      (dss) DNA compared to control cells. After 5-FU exposure, dss DNA decreased to 60
      75% in WiDr, WiDr/F and SW948 cells. Human IFN-alpha alone caused minimal DNA
      damage (95% dss DNA), but increased 5-FU-induced effects to 35-50% dss DNA. IFN
      gamma did not cause DNA damage and did not enhance 5-FU-mediated DNA damage.
      Expression of TS protein, analysed by ELISA, was increased after 5-FU exposure of
      SW948 cells, but this increase was not affected by addition of either IFN-alpha
      or IFN-gamma. It is concluded that one of the mechanisms involved in modulation
      of 5-FU activity is the effect of IFN-alpha on 5-FU-mediated DNA damage, but for
      IFN-gamma no mechanism of action was found.

PMID- 9155536
TI  - Paclitaxel as a radiosensitiser: a proposed schedule of administration based on
      in vitro data and pharmacokinetic calculations.
AB  - Paclitaxel is efficacious against many human cancers. Because it blocks cells at
      the radiosensitive G2-M interface, paclitaxel has been investigated as a
      radiosensitiser. The results have been equivocal and somewhat contradictory. It
      is impossible to obtain proper pharmacokinetic calculations, aimed at obtaining
      maximum cytotoxicity and/or radiosensitisation, without knowing (i) how long the
      drug must be in contact with the cells, (ii) how long the effect lasts after the
      drug is removed from the cellular environment, (iii) whether the drug acts as a
      radiosensitiser even when, like cis-platinum, it is added after the radiation and
      (iv) what the minimum quantity of drug in the cellular environment is required
      for both chemotoxicity and radiosensitisation. The present work addresses the
      above questions. Two radioresistant cell lines of human origin were used, A375
      melanoma and S549 lung carcinoma, in a clonogenic assay where only colonies with
      50 or more cells were counted. For the irradiation, 6 MV X-rays were used. Any G2
      M block was quantified by cell cycle kinetics analysis. From the results, a
      simulation of pharmacokinetics was conducted to calculate the schedule of
      administration of paclitaxel most likely to achieve and maintain significant
      chemotoxocity and radiosensitisation. The minimum concentration of paclitaxel for
      measurable cytotoxicity was 3 nM for both cell lines, but the drug was more toxic
      to the A549 cells. The minimum concentration for measurable radiosensitisation
      was 3 nM for A375 and approximately 0.1 nM for A549, but whereas above 3 nM the
      radiosensitivity increased in A375, it decreased above 1 nM for A549. A minimum
      of 18 h incubation with the drug was necessary for measurable effects and the
      radiosensitising effects were lost soon after its removal. There was no
      radiosensitisation if paclitaxel was added after the radiation, and, at the
      minimum effective concentrations, it caused only a minor and transient G2-M
      block. The pharmacokinetic calculations predict that 15 mg/m2 paclitaxel given as
      a 1 h infusion 5 days/week for 3 weeks during the radiotherapy should achieve
      both cytotoxicity and radiosensitisation. The mechanism of radiosensitisation by
      paclitaxel at the concentrations suggested by our results does not appear to be
      via a G2-M block and is probably concentration dependent. The results imply that
      low-dose, daily infusions of paclitaxel for as long as possible during a course
      of radiotherapy are more likely to result in radiosensitisation and prolonged
      cytotoxicity than high-dose infusions given once a week.

PMID- 9155535
TI  - Spontaneous development of plasmacytomas in a selected subline of BALB/cJ mice.
AB  - Sixty per cent of BALB/cAnPt mice injected intraperitoneally (i.p.) with
      tetramethylpentadecane (pristane) develop plasmacytomas (PCs), whereas less than
      10% of BALB/cJ develop such tumours. Most other mouse strains are completely
      resistant. Resistance is dominant over susceptibility in F1 hybrids between
      BALB/cAnPt and the resistant non-BALB/c strains, suggesting that susceptibility
      may be due to some genetic defect. (BALB/cAnPtxBALB/cJ)F1 hybrids have a PC
      incidence of 36-42%. Previously, BALB/cJ has been shown to harbour at least one
      resistance gene (Potter et al., Genomics 1988, Vol. 2, pp. 257-262). On the
      assumption that BALB/cJ may contain a segregating resistance gene, we cross
      BALB/cJ females with pristane-pretreated BALB/cJ males that were found to be
      carrying PC cells intraperitoneally 5-7 months after pristane treatment. After
      two selective crosses, 62% of the BALB/cJ subline BALB/cM2/22 developed PC after
      pristane and 52% after pristane followed by Abelson virus, while unselected
      controls had an incidence of 11% and 0%, respectively. Moreover, six spontaneous
      plasmacytomas developed in untreated females of the selected colony. Five of
      these carried T(12; 15) (F2; D2/3) translocations. The sixth had a T(1; 10) (G;
      C1) translocation and an interstitial duplication of segment (C1/E3) on one
      chromosome 5. It may be concluded that pristane treatment is not a prerequisite
      for the induction of the PC associated Ig/myc translocations.

PMID- 9155537
TI  - EORTC phase II study of daily oral linomide in metastatic renal cell carcinoma
      patients with good prognostic factors.
AB  - Following a previous EORTC GU-Group study, in which linomide showed some activity
      in poor prognosis patients, this study was initiated to determine the effect of
      linomide in more favourable patients. 35 patients with metastatic renal cell
      carcinoma with good prognostic factors, i.e. good performance status, prior
      nephrectomy, no prior systemic therapy, and no liver, bone or brain metastases,
      were treated with linomide, a quinoline derivative with immunomodulating
      properties, at a dose of 10 mg daily, after an initial dose escalation during the
      first 4 weeks of treatment. In 29 evaluable patients, no responses were observed
      (95% confidence interval 0-10%). Best overall response was no change in 9
      patients, for a median duration of 4 months. Linomide in this schedule was poorly
      tolerated, with 17% (6 patients) of patients being withdrawn and 23% (8 patients)
      having dose reductions due to adverse events, mostly influenza-like symptoms of
      myalgia, arthralgia and fatigue. Several cases of pericarditis and neuropathy
      were observed. In spite of selection of favourable prognosis patients and an
      optimal daily dosing schedule, linomide was not an effective treatment in renal
      cell carcinoma. In view of toxicity and lack of efficacy, there is no rationale
      in further testing the drug in this disease.

PMID- 9155539
TI  - Trofosfamide as a salvage treatment with low toxicity in malignant lymphoma. A
      phase II study.
AB  - 37 patients with disease progression after prior treatment for malignant lymphoma
      (27 low grade, 7 high grade and 3 Hodgkin's) were treated with oral trofosfamide
      daily. Most of these patients were heavily pretreated, with a median number of
      two regimens. Their median performance status was 1 (22 patients with 0-1 and 14
      with 2-3). The overall response rate was 49% (18/37; 3/37 CRs and 15/37 (41%)
      PRs). Median time to progression (TTP) from start of therapy was 4 months for
      patients with low-grade lymphoma and 2 months for high-grade lymphoma. For
      responding patients (CR + PR), TTP was approximately 10 and 7 months,
      respectively, for the two groups of lymphomas. Median survival from the start of
      treatment was 11 months (range 1.3-46.6) for low-grade lymphoma and 3.8 months
      (range 2.2-17.6) for high-grade lymphoma. Haematological and other toxicities
      were low and did not cause any major treatment interruptions. Trofosfamide is an
      interesting and a non-toxic palliative treatment for relapsing malignant
      lymphomas especially in elderly patients.

PMID- 9155538
TI  - An EORTC phase II study of the efficacy and safety of linomide in the treatment
      of advanced renal cell carcinoma.
AB  - The aim of this study was to determine the objective tumour response rate and
      duration of response and toxicity of linomide (Roquinimex) treatment in patients
      with disseminated renal cell carcinoma, pretreated or not pretreated with
      immunotherapy. From March 1991 to July 1992, 72 patients with metastatic and
      progressive renal cell cancer were entered of whom 9 (12%) were not evaluable for
      response. Linomide was given orally, twice weekly, 5 mg during the first week
      with dose escalation to 10 mg during the second week and 15 mg thereafter.
      Treatment was continued until disease progression or unacceptable toxicity. No
      haematological toxicity but slight anaemia was observed. A significant WBC (white
      blood cell count) increase (P < 0.0001, paired T-test) was found during
      treatment. The most often reported non-haematological side-effects were: flu-like
      syndrome (54%, grade III-IV 7%), nausea/vomiting (41% and 3%, respectively) and
      neurotoxicity (34% and 2%). Most side-effects were of mild or moderate intensity
      (WHO grade 1 or 2). The objective overall response rate was 4%: 1 CR and 2 PRs.
      Stable disease was reported for 28 patients (40%). The duration of response was
      17, 22 and 30 (CR) months. Median time to progression was 5 months. Linomide at
      the given dose and schedule is well tolerated, but has limited antitumour
      activity in metastatic renal cell carcinoma.

PMID- 9155540
TI  - A phase I study of irinotecan and infusional cisplatin with recombinant human
      granulocyte colony-stimulating factor support in the treatment of advanced non
      small cell lung cancer.
AB  - We conducted a phase I study to examine whether support with recombinant human
      granulocyte colony-stimulating factor (rG-CSF) would permit dose intensification
      of irinotecan (CPT-11) in combination with cisplatin (20 mg/m2 x 5 days) in non
      small cell lung cancer (NSCLC) patients. CPT-11 was administered by bolus
      infusion at a starting dose of 100 mg/m2 on day 1, followed by serial increments
      at 20 mg/m2, given every 4 weeks. The major toxic effects were granulocytopenia
      and diarrhoea. The response rate was 55% (11/20). The optimum dose for phase II
      studies appears to be 20 mg/m2/day (5-day continuous infusion) for cisplatin and
      160 mg/m2 (day 1) for CPT-11 with rG-CSF support in NSCLC.

PMID- 9155541
TI  - Comments on Health-related quality of life of adults surviving malignancies in
      childhood, Apajasalo et al., Eur J Cancer, 32A, No. 8, pp. 1354-1358, 1996.

PMID- 9155542
TI  - Breast cancer and HIV infection: two case reports.

PMID- 9155543
TI  - Intramedullary spinal cord metastasis from carcinoma of the lung: detection by
      positron emission tomography.

PMID- 9155544
TI  - Primary mediastinal seminoma.

PMID- 9155545
TI  - How can industry, academia, public health authorities and the Sexually
      Transmitted Diseases Diagnostics Initiative (SDI) work together to help control
      sexually transmitted diseases in developing countries?

PMID- 9155546
TI  - Can the management of gonorrhoea be improved?

PMID- 9155547
TI  - Adverse effects and drug interactions of medications commonly used in the
      treatment of adult HIV positive patients: Part 2.

PMID- 9155548
TI  - Epidemiological treatment and tests of cure in gonococcal infection: evidence for
      value.
AB  - OBJECTIVES: To evaluate the evidence for value of using epidemiological treatment
      and of using tests of cure in the management of gonococcal infections. METHODS:
      Medline was used to search the literature for well-conducted studies that had a
      bearing on the evaluation of these issues. CONCLUSIONS: Epidemiological treatment
      is treatment given to named contacts of patients after a history of exposure to
      disease but without or in advance of confirmatory pathological findings. It may
      be given when the clinician considers that the risk to the patient of unnecessary
      treatment is outweighed by the risk of complications of the infection or the
      probability of transmission of the infection to other contacts. It may be
      appropriate where detection by microscopy is relatively unreliable such as when
      infection of the cervix, rectum, or pharynx is suspected. If epidemiological
      treatment is given, then it does not obviate the need for confirmatory tests to
      be sent, tests of cure to be done, or for contact tracing. At least one test of
      cure is mandatory following treatment of gonorrhoea. The test of cure in women
      should include a blind rectal swab. For infection of the pharynx and rectum the
      chances of a false negative test of cure are higher and, therefore, more than one
      test of cure is required. An additional test of cure is also necessary in
      patients with salpingitis or disseminated gonococcal infection. This paper is a
      discussion of two interrelated issues in the management of gonorrhoea. It is
      based on two presentations by the author at a workshop organised by Dr Mark
      Fitzgerald entitled Development of audit measures and guidelines for good
      practice in the management of gonorrhoea and held at the Royal College of
      Physicians, London, in May 1995. The conclusions reached are based on the
      consensus view of the participants. For simplicity the two issues are dealt with
      consecutively.

PMID- 9155549
TI  - The diagnosis of oropharyngeal gonorrhoea.

PMID- 9155551
TI  - What is normal vaginal flora?
AB  - OBJECTIVE: To observe the composition of the vaginal flora of healthy women over
      time, and in relation to hormonal changes, sexual activity, and hygiene habits.
      DESIGN: A longitudinal surveillance of the vaginal flora over an eight week
      period. SUBJECTS: 26 female health care workers in local genitourinary medicine
      clinics. METHODS: The participants were anonymised. They filled in diary cards
      daily. Blind vaginal swabs were self-taken two-seven times weekly. A smear was
      air-dried for later Gram staining. The swabs were also cultured for Candida spp,
      Gardnerella vaginalis, anaerobes, Mycoplasma hominis and Ureaplasma urealyticum.
      RESULTS: Of 26 subjects, only four had normal vaginal microbiology throughout.
      One woman, who was not sexually active, had bacterial vaginosis (BV) throughout
      and nine (35%) had intermittent BV. Candidiasis was found intermittently in eight
      women (31%), and eight had normal microscopy. U urealyticum was isolated
      intermittently in 40% of women with BV, 25% with candida, and 50% with normal
      microscopy. Many women were symptomatic, but symptoms correlated poorly with
      microbiological findings. All but two women were sexually active; however, more
      women with BV were exposed to semen. BV seemed to be related to frequent use of
      scented soap, and there appeared to be an additive effect of clothing and hygiene
      factors. CONCLUSIONS: Our study raises doubts about what should be regarded as
      normal vaginal flora. It calls into question the significance of finding BV or U
      urealyticum on a single occasion in asymptomatic women, or of finding normal
      flora in symptomatic women. The effect of external factors on the vaginal flora
      deserve further study.

PMID- 9155550
TI  - Sexually transmitted diseases in mobile populations.

PMID- 9155552
TI  - Sentinel surveillance of Chlamydia trachomatis infection in women terminating
      pregnancy.
AB  - AIMS: To evaluate demographic characteristics of women terminating their
      pregnancy for sentinel surveillance of Chlamydia trachomatis infection and to
      report changing prevalences of C trachomatis over time within this study
      population. DESIGN: Screening for C trachomatis in women seeking induced abortion
      was introduced in 1984 at the Department of Gynecology, Regional Hospital,
      Trondheim, Norway. Over the study years our department has used a precoded
      medical record covering sociodemographic, medically relevant data, also recording
      outcome of the C trachomatis test. Throughout the study the Department of
      Microbiology applied cell culture, enzyme immunoassay, and, during the most
      recent years a nucleic acid test to identify C trachomatis. STATISTICAL METHODS:
      Chi square test for linear trend and unconditional logistic regression. RESULTS:
      Over the study period, women having induced abortion were characterised by being
      most often single and more often at younger age. The overall age-adjusted
      prevalence of C trachomatis declined from 9.2% in 1985 to 3.6% in 1995, the major
      decline occurring from 1987 to 1991, and affected all age-groups simultaneously.
      There was a 60% decrease in odds ratio of having a C trachomatis infection from
      1985 to 1991, and the crude and the adjusted odds ratios did not differ for any
      year examined. CONCLUSION: Women deciding on pregnancy termination have
      demographic characteristics that identify high-risk groups for C trachomatis
      infection. Despite these characteristics, which were relatively constant over the
      study period, the study population changed from being a high- to a low-prevalence
      population of C trachomatis.

PMID- 9155553
TI  - STD rapid assessment in Rwandan refugee camps in Tanzania.
AB  - OBJECTIVE: To obtain baseline information on sexually transmitted diseases (STDs)
      in the Rwandan refugees camps in Tanzania, prior to establishment of STD
      services. SETTING: The largest camps of Rwandan refugees in the Ngara District of
      Tanzania (estimated population 300,000). The study was carried out in 8 days in
      August 1994. SUBJECTS AND METHODS: A rapid assessment technique was used to
      measure STD prevalences among: (i) 100 antenatal clinic attenders (ANC); (ii) 239
      men from outpatient clinics (OPD); and (iii) 289 men from the community.
      Interviews (by questionnaire) and genital examination were performed for all
      participants; sampling for females included genital swabs for the the diagnosis
      of Neisseria gonorrhoeae (NG), Candida albicans (CA), Trichomonas vaginalis (TV),
      bacterial vaginosis (BV) and a blood sample for syphilis serology. Men provided
      urine samples which were screened for leucocytes using the leucocyte esterase
      (LE) dipstick; urethral swabs for Gram stain were taken from men with a reactive
      LE test and from those with symptoms or signs of urethritis. OPD males provided a
      blood sample for syphilis serology. RESULTS: All groups reported frequent
      experience with STDs and engaging in risky sexual behaviour prior to the survey.
      During the establishment of the camps, sexual activity was reportedly low. Over
      50% of ANC attenders were infected with agents causing vaginitis (TV/BV/CA) and
      3% were infected with NG. The prevalence of active syphilis was 4%. In the male
      outpatients, the prevalence of urethritis was 2.6% and of serological syphilis
      was 6.1%. Among males in the community, the prevalence of urethritis was 2.9%
      (the majority being asymptomatic infections). We noted frequent over-reporting of
      STD symptoms, unconfirmed clinically or biologically. CONCLUSIONS: STD case
      detection and management should be improved by training health workers in using
      the WHO syndromic approach, and through IEC campaigns encouraging attendance at
      clinics. Rapid epidemiological methods provide quick and useful information at
      low cost in refugee camps.

PMID- 9155554
TI  - Risk factors for sexually transmitted diseases among women attending family
      planning clinics in Dar-es-Salaam, Tanzania.
AB  - BACKGROUND: Identification of risk factors for sexually transmitted diseases
      (STDs) assists in development of treatment algorithms, which are potentially
      important components of STD control when microbiologic facilities are limited.
      METHODS: A cross-sectional study was performed to assess STD and HIV risk factors
      of 2285 women attending three family planning clinics in Dar-es-Salaam, Tanzania
      during 1991-92. Women were interviewed and examined for signs of STDs. Specimens
      were taken for laboratory diagnosis of HIV, other sexually transmitted organisms,
      and Candida albicans. RESULTS: The prevalence of gonorrhoea was found to be 4.2%,
      prevalence of trichomoniasis was 14.3%, and positive syphilis serology was found
      in 2.5% of women. Unmarried women were at increased risk of trichomoniasis (age
      adjusted OR = 1.48 95% CI [1.12, 1.95]), gonorrhoea (age-adjusted OR = 1.81 95%
      CI [1.14, 2.86]) and syphilis (age-adjusted OR 1.5 [0.84, 2.68]). An increasing
      number of sexual partners in the past five years was associated with an increased
      risk of all STDs. Current use of the oral contraceptive pill was positively
      associated with gonorrhoea, multivariate OR = 1.75 95% CI [1.05, 2.93]. The
      prevalence of candidiasis was 11.5% and was not associated with any of the
      demographic or behavioural risk factors examined. Clinical diagnostic algorithms
      for STDs in this study population had relatively low sensitivity and low positive
      predictive value. CONCLUSION: Being unmarried and having a higher number of
      sexual partners were consistently associated with each STD, while the
      associations for other risk factors varied between STDs, emphasising the
      complexity of STD distribution. Further development of diagnostic algorithms and
      other methods for screening women for STDs are needed to reduce the impact of
      STDs and HIV in developing countries.

PMID- 9155555
TI  - Survival and treatment of AIDS patients 1984-1993: experience of a smaller east
      London HIV centre.
AB  - OBJECTIVE: To assess changes in survival from diagnosis of AIDS for patients
      managed in a small East London HIV clinic and the impact of therapeutic
      interventions on these survival patterns. DESIGN: Prospective observational
      study. SETTING: Grahame Hayton Unit, Royal London Hospital. SUBJECTS: 156 AIDS
      patients managed between 1984 and 1993. MAIN OUTCOME MEASURE: Survival from
      diagnosis of AIDS. RESULTS: Median survival for those diagnosed with AIDS before
      1 January 1987 was 9.4 months compared with 27.2 months after 1 January 1987
      (logrank chi 2 = 10.3, p = 0.001): CD4 count at time of AIDS and treatment with
      zidovudine or PCP prophylaxis were significantly associated with survival from
      time of AIDS. Of the 156 AIDS patients, 93 had been treated with zidovudine
      sometime during their follow up, 60 had received primary and 50 secondary
      Pneumocystis carinii pneumonia (PCP) prophylaxis. After controlling for gender,
      sexual orientation, age at time of AIDS, CD4 count at time of AIDS, diagnosis
      when first presenting to the clinic (AIDS/non-AIDS) and year of AIDS diagnosis,
      all patients who received either zidovudine or PCP prophylaxis had significant
      reductions in the risk of dying compared with those who received neither PCP
      prophylaxis nor zidovudine: a reduction in risk of dying between 71% (95% CI 40%
      to 86%) and 83% (95% CI 50% to 94%) was observed depending on the combination of
      zidovudine and PCP prophylaxis. CONCLUSION: A debate is currently taking place
      about the format and value of HIV service provision with increasing numbers of
      HIV infected individuals managed at smaller HIV clinics. Larger clinics
      concentrate clinical expertise on a single site and facilitate clinical trials.
      Smaller well run HIV units staffed by competent health professionals not only
      provide clinical outcomes similar to those obtained in the larger centres, but
      may also allow a more informal and intimate setting for HIV infected individuals
      who want to be treated nearer their area of residence.

PMID- 9155556
TI  - HIV partner notification policy and practice within GUM clinics in England: where
      are we now?
AB  - OBJECTIVES: To evaluate the extent to which larger genitourinary medicine (GUM)
      clinics in England have established local clinic policies for HIV Partner
      Notification (PN) and to describe the process of HIV PN within this setting.
      DESIGN: A cross-sectional survey of HIV PN policies and practices within GUM
      clinics. SUBJECTS AND SETTING: Senior consultants in 59 GUM clinics in England.
      MAIN OUTCOME MEASURES: The presence of clinic policies for HIV PN, indicators of
      HIV PN activity (that is, its initiation, documentation, performance and
      evaluation) and factors hindering the acceptance of HIV PN into clinical
      practice. RESULTS: Only 18% (10/57) of respondents stated that their clinics had
      developed their own local policies for HIV PN. Fifteen percent (9/58) of clinics
      had audited HIV PN activity, 15% had provided specific HIV PN training for
      doctors and 47% (27/58) for health advisers. Within GUM clinics, health advisers
      play a key role in the HIV PN process, being responsible for initiating the
      discussion of partners, patient follow-up and documenting HIV PN activity in
      patients' notes. Notifying partners was primarily seen as the responsibility of
      the newly diagnosed HIV positive patient. Although 77% (43/56) of responding
      consultants believed that HIV PN had become an accepted part of their clinics'
      practice, the perceived unacceptability of HIV PN to patients and health care
      workers were seen as important limiting factors. CONCLUSION: In many GUM clinics,
      local policies on HIV PN have yet to be established and appropriate training for
      the health personnel provided. Nevertheless, there appears to be wide-spread
      acceptance of HIV PN in clinical practice with an acknowledgement of its limiting
      factors. Further research into the acceptability of HIV PN to health care workers
      and patients in this setting should be undertaken.

PMID- 9155557
TI  - Abnormal expression and mutation of p53 in cervical cancer--a study at protein,
      RNA and DNA levels.
AB  - OBJECTIVES: The objectives of this study are to document the status of p53
      expression and mutation in cervical cancer at protein, RNA and DNA levels and to
      relate this to the presence of HPV. MATERIALS AND METHODS: Biopsy specimens from
      one hundred and three squamous cell carcinoma of the cervix and histologically
      normal ectocervix were analysed. Fresh tissues were extracted for protein, RNA
      and DNA and flash frozen tissue cryostat sectioned for immunohistochemical
      staining. HPV DNA status was determined by PCR using L1 consensus primers and
      typed for HPV 16 and 18 with E6 specific primers. p53 expression was determined
      at the protein level by Western blotting on protein extracts and at RNA level by
      Northern blotting. RESULTS: There was no p53 overexpression or mutation
      detectable in the protein extracts. Three of 65 (4.6%) of the carcinomas were
      positive for p53 by immunostaining with the polyclonal antibody CM1.
      Overexpression at the RNA level was detected in 2 of 32 (6.3%) carcinomas. p53
      mutation was screened for by PCR/SSCP (single strand conformation polymorphism)
      followed by sequencing to define the site of mutation. Two of the cervical
      cancers (2.0%) showed mutation in p53 in exons 7 or 8. The mutation rate in HPV
      positive tumours was 1.2% (1/81) and in HPV negative tumours was 5.2% (1/19).
      CONCLUSION: p53 overexpression or mutation does not seem to play a significant
      role in cervical carcinomas.

PMID- 9155558
TI  - Non-cultural detection of rectal and pharyngeal gonorrhoea by the Gen-Probe PACE
      2 assay.
AB  - OBJECTIVE: To assess the sensitivity and specificity of the Gen-Probe PACE 2
      assay, which uses a chemiluminescent labelled single-stranded DNA probe to detect
      gonococcal ribosomal RNA (rRNA), for the non-cultural detection of rectal and
      pharyngeal gonorrhoea in homosexual men. SUBJECTS: 161 homosexual men attending
      the Department of Genitourinary Medicine, Edinburgh Royal Infirmary during the
      latter half of 1995 and the first quarter of 1996. METHODS: Duplicate rectal and
      pharyngeal swabs were collected for culture on modified New York City (MNYC)
      medium and detection of gonococcal nucleic acid by the Gen-Probe assay.
      Repeatedly reactive Gen-Probe specimens from culture negative patients were also
      tested by the Gen-Probe competition assay (PCA). RESULTS: Of the 161 patients, 23
      (14.3%) gave a positive culture at one or both sites (rectum 10, throat 8, rectum
      and throat 5) compared with 28 (16.7%) who gave a positive Gen-Probe result at
      one or both sites (rectum 9, throat 11, rectum and throat 8). After resolution of
      discrepant results by PCA the sensitivity, specificity, positive predictive value
      (PPV) and negative predictive value (NPV) of Gen-Probe was 94.1%, 100%, 100% and
      99.3% for rectal specimens while the corresponding values for pharyngeal
      specimens were 86.4%, 100%, 100%, and 97.9%. The sensitivity and NPV of rectal
      culture were 88.2% and 98.6% while the corresponding values for pharyngeal
      culture were 59% and 93.9%. Gen-Probe was significantly more sensitive than
      throat culture (p < 0.05) but not rectal culture (p > 0.2). The average Relative
      Light Units (RLU) value for the cut-off was 386 (range 351-450) while the average
      for a positive result was 20306 (range 403-110104): this was, however,
      significantly higher (p = 0.019) in rectal specimens 31325 (range 1705-110104)
      than in throat specimens 10447 (range 403-15633). CONCLUSIONS: Gen-Probe PACE 2
      assay is a sensitive and specific method for the detection of rectal and
      pharyngeal gonorrhoea. As the Gen-Probe assay may detect nucleic acid from non
      viable gonococci the clinical significance of a probe positive culture negative
      specimen from a patient without culture evidence of gonorrhoea at another site is
      uncertain and requires further consideration. Nevertheless a positive result does
      indicate exposure to infection and could be important in ensuring appropriate
      partner notification action. If non-cultural methods are used to screen for
      gonococcal infection cultures should be obtained from patients with positive
      results in order that the antibiotic susceptibility and molecular epidemiology of
      the gonococcal population can be monitored.

PMID- 9155559
TI  - Recurrent respiratory papillomatosis with pulmonary cystic disease in a child,
      following maternal genital warts.
AB  - Human papillomavirus (HPV) infection of the genital tract is associated with the
      development of genital warts. A causal link between maternal HPV infection and
      development of laryngeal papillomatosis in the offspring has been proposed. We
      report a case of pulmonary cystic disease, a rare but serious complication of
      laryngeal papillomatosis in a child, following maternal genital warts.

PMID- 9155560
TI  - HIV infection with haemolytic anaemia.

PMID- 9155561
TI  - Searching for the evidence.

PMID- 9155562
TI  - Genitourinary medicine and The Internet No. 4.
AB  - The Internet provides a rapid facility for accessing a large amount of
      information which, once found, can be manipulated in a variety of ways. For
      example, with the authors' permission, Web pages can be retrieved, converted into
      text files and edited to produce patient leaflets of sexually-transmitted
      conditions, prescribing information leaflets, clinical guidelines and protocols,
      etc. Collections of relevant Web sites placed in bookmarks on a Web browser for
      students to refer to could also form the basis for self-directed learning, and
      tutorials and small group teaching on specific subjects.

PMID- 9155563
TI  - Imported syphilis and other sexually transmitted infections among UK travellers
      to Russia and Poland.

PMID- 9155564
TI  - Sexually transmitted diseases in South Africa: epidemic donovanosis in Durban?

PMID- 9155565
TI  - Multidrug resistant tuberculosis: practical lesson for HIV units.

PMID- 9155567
TI  - Regional expression of intestinal genes for nutrient absorption.

PMID- 9155566
TI  - Role of cytokines and their inhibitors in acute pancreatitis.

PMID- 9155568
TI  - Evaluation of Helicobacter pylori in reflux oesophagitis and Barrett's
      oesophagus.
AB  - BACKGROUND: One of the major pathophysiological abnormalities in patients with
      gastro-oesophageal reflux disease is thought to involve transient lower
      oesophageal sphincter (LOS) relaxations. One component of the neural mechanism
      controlling the LOS appears to be a reflex are whose afferent limb originates in
      the gastric fundus. As inflammation is known to be associated with neural
      activation an investigation was made to determine whether gastric infection with
      H pylori is altered in prevalence or distribution in patients with reflux
      disease. METHODS: Five groups of subjects referred for endoscopy-group 1: 25
      controls (asymptomatic individuals with anaemia and normal endoscopy); group 2:
      36 subjects with erosive oesophagitis alone (Savary-Millar grades I-III); group
      3: 16 subjects with duodenal ulcer alone; group 4: 15 subjects with oesophagitis
      with duodenal ulcer; group 5: 16 subjects with Barrett's oesophagus. No patients
      were receiving acid suppressants or antibiotics. An antral biopsy specimen was
      taken for a rapid urease test, and two biopsy specimens were taken from the
      antrum, fundus, and oesophagus (inflamed and non-inflamed) for histological
      evidence of inflammation and presence of H pylori using a Giemsa stain. RESULTS:
      Nine (36%) controls had H pylori. Patients with duodenal ulcer alone had a
      significantly higher incidence of colonisation by H pylori than other groups
      (duodenal ulcer 15 (94%); oesophagitis 13 (36%); oesophagitis+duodenal ulcer 6
      (40%); Barrett's oesophagus 4 (25%)). H pylori was not more common in
      oesophagitis. When H pylori colonised the gastric antrum it was usually found in
      the gastric fundus. There was no difference in anatomical distribution of H
      pylori in the different patient groups. In Barrett's oesophagus H pylori was
      found in two of 16 in the metaplastic epithelium. CONCLUSION: H pylori is not
      more common and its distribution does not differ in those with oesophagitis
      compared with control subjects, and is therefore unlikely to be aetiologically
      important in these patients. H pylori, however, can colonise Barrett's
      epithelium.

PMID- 9155569
TI  - Effect of N alpha-methyl-histamine on acid secretion in isolated cultured rabbit
      parietal cells: implications for Helicobacter pylori associated gastritis and
      gastric physiology.
AB  - BACKGROUND: Helicobacter pylori has been shown to produce the unusual metabolite
      N alpha-methyl-histamine. This compound is known to be a potent agonist at
      inhibitory histamine H3 receptors. There is increasing evidence implicating this
      receptor in the control of gastric acid secretion but the mechanism for this
      remains to be clarified. AIMS: To investigate the effect of N alpha-methyl
      histamine on the acid secretory activity of parietal cells and to determine the
      mechanism for such effects, thus helping to determine the role of this compound
      in the pathophysiology of H pylori infection. METHODS: Rabbit parietal cells were
      isolated and enriched by collagenase-EDTA digestion and centrifugal elutriation.
      Following culture on Matrigel coated plates, acid secretion was assessed by 14C
      aminopyrine accumulation. RESULTS: N alpha-methyl-histamine (100 microM) was as
      potent as histamine (100 microM) in stimulating acid secretion. This effect was
      reversed by ranitidine indicating it was mediated via the H2 receptor. N alpha
      methyl-histamine potentiated the effects of both carbachol (increased by 280%)
      and gastrin (by 350%) (p < 0.01). N alpha-methyl-histamine had no inhibitory
      actions on forskolin or carbachol stimulated acid secretion suggesting that there
      is not an inhibitory H3 receptor located directly on the parietal cell.
      CONCLUSIONS: Bacterially produced N alpha-methyl-histamine directly stimulates
      acid secretion by parietal cells and this may contribute to the increased acid
      secretion that contributes to duodenal ulceration.

PMID- 9155570
TI  - Role of Helicobacter pylori surface structures in bacterial interaction with
      macrophages.
AB  - BACKGROUND: Helicobacter pylori infection is associated with a marked
      infiltration of the gastric epithelium by neutrophils, macrophages, lymphocytes,
      and plasma cells. Despite the presence of phagocytes in close vicinty to H pylori
      microbes a great number of people are unable to eradicate bacteria. AIMS: To
      investigate the involvement of multiple bacterial 'adhesins' and some phagocytic
      receptors in the process of the ingestion of H pylori by macrophages. BACTERIA: H
      pylori strains differing in the expression of sialic acid dependent (sHA) or
      sialic acid independent (HA) haemagglutinin and heparan sulphate binding were
      selected for the study. METHODS: The uptake of fluorescein labelled H pylori
      bacteria by a homogenous macrophage cell line J 774A.1 was estimated in a
      quantitative fluorometric assay. RESULTS: The ingestion of H pylori 17874 and 25
      strains expressing sHA was inhibited by the pretreatment of the bacteria with
      anti-sHA antibodies or fetuin as well as by treatment of the macrophages with
      neuraminidase. In contrast the uptake of H pylori 17875 strain expressing HA
      remained unchanged. The phagocytosis of all investigated bacteria was inhibited
      after the treatment with heparin, hyaluronic acid or vitronectin with fresh but
      not heat inactivated serum. CONCLUSIONS: The results suggest that H pylori
      surface compounds binding host proteins such as fetuin, heparin/haparan sulphate,
      hyaluronic acid, and vitronectin in the presence of complement, could allow the
      bacteria to avoid phagocytosis.

PMID- 9155572
TI  - Studies on gastric mucosal microcirculation. 1. The nature of regional variations
      induced by ethanol injury.
AB  - BACKGROUND/AIMS: The focal nature of gastric ulcers raises the possibility of
      underlying regional disturbances in gastric mucosal microcirculation. This study
      employed fluorescent in vivo microscopy with the aim of directly investigating
      the response of several areas of the gastric mucosa to 60% ethanol. METHODS:
      Changes in macromolecular leakage of fluorescein labelled albumin, vessel
      diameter, and acridine red labelled leucocyte adhesion and rolling were assessed
      over a period of two hours. A total of 0.5 ml 60% ethanol was topically applied
      for five minutes to the exteriorised gastric mucosa of anaesthetised rats. RATS:
      Three distinct patterns of response were found. Areas of lesion formation were
      small and occurred within five minutes. These areas showed persistent blood flow
      stasis throughout the course of the experiment, increased leakage (p < 0.02), and
      no leucocyte adhesion. Peripheral to the lesion, sustained leakage (p < 0.02) was
      found with adherence of leucocytes (p < 0.01) after lesion formation. Sites more
      remote to any lesion showed transient leakage and significant numbers of
      'rolling' leucocytes (p < 0.01) were observed again after the lesion had formed.
      CONCLUSIONS: Despite widespread exposure of the entire gastric mucosa to 60%
      ethanol the resultant mucosal injury was limited. Widespread vascular damage was
      found reflected by macromolecular leakage, the pattern of which showed regional
      variation.

PMID- 9155571
TI  - Synthesis and activity of Helicobacter pylori urease and catalase at low pH.
AB  - BACKGROUND: Helicobacter pylori produces large amounts of urease presumably to be
      prepared for the rare event of a sudden acid exposure. The hypothesis that H
      pylori is acid sensitive and protein production is inhibited by low pH was
      examined. METHODS: H pylori or its soluble enzymes were incubated buffered or
      unbuffered at a pH ranging from 2-7 in the presence of 5 mM urea for 30 minutes.
      After exposure, urease and catalase activities of whole cells, supernatants, and
      soluble enzyme preparations were measured at pH 6.8. Newly synthesised enzyme was
      quantified by immunoprecipitation of [35S]-methionine labelled protein. RESULTS:
      Exposure to buffer below pH 4 resulted in loss of intracellular urease activity.
      In soluble enzyme preparations and supernatant, no urease activity was measurable
      after incubation at pH < 5. In contrast, catalase in whole cells, supernatant,
      and soluble enzyme preparations remained active after exposure to pH > or = 3.
      Exposure below pH 5 inhibited synthesis of total protein including nascent urease
      and catalase. At pH 6 or 7, urease represented 10% of total protein, catalase
      1.5%. Exposure of H pylori to unbuffered HCl (pH > 2) resulted in an immediate
      neutralisation; urease and catalase activities and synthesis were unchanged.
      CONCLUSION: Low surrounding pH reduces activity of urease and synthesis of
      nascent urease, catalase, and presumably of most other proteins. This suggests
      that H pylori is not acidophilic although it tolerates short-term exposure to low
      pH.

PMID- 9155573
TI  - Efficacy of primed infusions with high dose ranitidine and omeprazole to maintain
      high intragastric pH in patients with peptic ulcer bleeding: a prospective
      randomised controlled study.
AB  - BACKGROUND: In healthy subjects, continuous infusions of high dose ranitidine and
      omeprazole produce high intragastric pH values. AIM: To test the hypothesis that
      both drugs also maintain high intragastric pH values in patients with bleeding
      ulcers. PATIENTS AND METHODS: In two parallel studies, 20 patients with bleeding
      duodenal ulcers and 20 patients with bleeding gastric ulcers were randomly
      assigned to receive either ranitidine (0.25 mg/kg/hour after a bolus of 50 mg) or
      omeprazole (8 mg/hour after a bolus of 80 mg) for 24 hours. Intragastric pH was
      continuously recorded with a glass electrode placed 5 cm below the cardia.
      RESULTS: Both drugs rapidly raised the intragastric pH above 6. During the second
      12 hour period, however, the percentage of time spent below a pH of 6 was 0.15%
      with omeprazole and 20.1% with ranitidine (p = 0.0015) in patients with duodenal
      ulcer; in patients with gastric ulcer it was 0.1% with omeprazole and 46.1% with
      ranitidine (p = 0.002). CONCLUSIONS: Primed infusions of omeprazole after a bolus
      produced consistently high intragastric pH values in patients with bleeding
      peptic ulcers, whereas primed infusions with ranitidine were less effective
      during the second half of a 24 hour treatment course. This loss of effectiveness
      may be due to tolerance.

PMID- 9155574
TI  - Cytokine effects on pepsinogen secretion from human peptic cells.
AB  - BACKGROUND: Different cytokines, including epidermal growth factor (EGF) and
      interleukin 1 beta (IL 1 beta), participate in the pathogenesis of gastric
      mucosal damage and repair by means of different mechanisms that are either
      paracrine or autocrine in nature. AIMS: To study whether EGF and IL 1 beta affect
      pepsinogen secretion in vitro. METHODS: Dispersed human peptic cells were
      prepared from endoscopically obtained biopsy specimens after collagenase
      digestion, mechanical disruption, and density gradient centrifugation. RESULTS:
      EGF dose dependently increased basal pepsinogen secretion and mitogenic
      concentrations (0.1 nM) of EGF induced submaximal stimulation. Similar effects
      were observed with transforming growth factor alpha. EGF effects on pepsinogen
      secretion were in addition to that induced by CCK-OP and db-cAMP stimulated
      pepsinogen secretion. EGF stimulated pepsinogen secretion was completely
      inhibited by a human immunospecific EGF receptor antibody and reduced by both
      genistein and tyrphostin-25, two different tyrosine kinase inhibitors. IL 1 beta
      does not affect basal, CCK-OP or acetylcholine stimulated pepsinogen secretion.
      However, IL 1 beta dose dependently inhibited db-cAMP and histamine stimulated
      pepsinogen secretion. CONCLUSIONS: These results show that both EGF and IL 1 beta
      modulate human pepsinogen secretion in vitro and suggest that the paracrine
      effects of these cytokines on pepsinogen secretion might be involved in some
      pathological conditions of damage and inflammation of the gastric mucosa.

PMID- 9155575
TI  - Alcoholic beverages produced by alcoholic fermentation but not by distillation
      are powerful stimulants of gastric acid secretion in humans.
AB  - BACKGROUND: The effect of commonly ingested alcoholic beverages on gastric acid
      output and release of gastrin in humans is unknown. AIM AND METHODS: In 16
      healthy humans the effect of some commonly ingested alcoholic beverages produced
      by fermentation plus distillation (for example, whisky, cognac, calvados,
      armagnac, and rum) or by alcoholic fermentation (beer, wine, champagne, martini,
      and sherry) on gastric acid output and release of gastrin was studied. Gastric
      acid output was determined by the method of intragastric titration. Plasma
      gastrin was measured using a specific radioimmunoassay. RESULTS: None of the
      alcoholic beverages produced by fermentation plus distillation had any
      significant effect on gastric acid output and release of gastrin compared with
      control (isotonic glucose and distilled water). Alcoholic beverages produced only
      by fermentation significantly (p < 0.05) increased the gastric acid output by 57%
      to 95% of maximal acid output (MAO) and release of gastrin up to 5.1-fold
      compared with control. If beer, wine, and sherry were distilled, only their
      remaining parts increased gastric acid output by 53% to 76% of MAO and increased
      release of gastrin up to 4.3-fold compared with control. CONCLUSIONS: (1)
      Alcoholic beverages produced by fermentation but not by distillation are powerful
      stimulants of gastric acid output and release of gastrin; (2) the alcoholic
      beverage constituents that stimulate gastric acid output and release of gastrin
      are most probably produced during the process of fermentation and removed during
      the following process of distillation.

PMID- 9155577
TI  - Twenty years of childhood coeliac disease in The Netherlands: a rapidly
      increasing incidence?
AB  - BACKGROUND: The incidence of coeliac disease varies internationally. AIMS: To
      assess the incidence of childhood coeliac disease in The Netherlands and to study
      the clinical features and the presence of associated disorders. SUBJECTS:
      Identified cases of childhood coeliac disease in The Netherlands in 1993-4 by
      means of the Dutch Paediatric Surveillance Unit. METHODS: Inclusion criteria were
      born in The Netherlands, diagnosed with at least one biopsy of the small bowel in
      1993-4 and age at diagnosis 0-14 years. The data were cross checked by the Dutch
      Network and National Database of Pathology and compared with data from a previous
      study on childhood coeliac disease, 1975-90. RESULTS: A total of 193 coeliac
      patients were identified by means of the Surveillance Unit, another 20 through
      the National Database of Pathology. The mean crude incidence rate of diagnosed
      childhood coeliac disease was 0.54/1000 live births, which is in the range of
      rates found in other western European countries and significantly higher than the
      mean crude incidence rate of 0.18/1000 live births found in The Netherlands in
      1975-90. The clinical presentation was classic: chronic diarrhoea, abdominal
      distension, and growth failure. Associated disorders were present in 11.7% of the
      cases. CONCLUSIONS: The incidence of diagnosed childhood coeliac disease in The
      Netherlands seems to have increased significantly during the past few years. In a
      period of 20 years no significant changes could be found in the clinical picture
      at preentation of coeliac disease in Dutch children.

PMID- 9155576
TI  - The trophic action of growth hormone, insulin-like growth factor-I, and insulin
      on human duodenal mucosa cultured in vitro.
AB  - BACKGROUND: Experimental evidence suggests that hormones may regulate small
      intestinal adaptation after surgical resection. AIMS: To characterise the effect
      of recombinant human growth hormone (GH), insulin-like growth factor-I (IGF-I)
      and insulin on crypt epithelial cell proliferation in the human duodenal mucosa
      cultured in vitro. PATIENTS: Thirty nine adults had endoscopic duodenal biopsy
      specimens taken, which were histologically normal and pair matched specimens from
      each patient acted as their own control. METHODS: Paired biopsy specimens from
      patients were cultured in vitro, with or without the addition of GH (0.004
      IU/ml), IGF-I (400 ng/ml) or insulin (50 micrograms/ml), alone or in combination.
      After 22 hours, vincristine sulphate was added to the cultures and three hours
      later specimens were removed and fixed, and DNA stained by the Feulgen method.
      Intestinal crypts were microdissected and crypt epithelial cell proliferation
      determined by estimating mean numbers of accumulated metaphase arrests/crypt
      present in tests and controls between 22-25 hours of culture. RESULTS: The
      addition of GH, IGF-I, and insulin, alone or in combination, significantly
      increased crypt epithelial cell proliferation in test explants compared with
      controls. IGF-I was most potent and its trophic effect was modified by insulin.
      CONCLUSIONS: GH, IGF-I, and insulin are involved in the regulation of crypt cell
      proliferation in the human small intestine in vitro and possibly in vivo.

PMID- 9155578
TI  - Enteral supplementation with ornithine alpha ketoglutarate improves the early
      adaptive response to resection.
AB  - BACKGROUND: Polyamine synthesis or uptake, or both, might be an important event
      that initiates the adaptive hyperplasia seen in the intestinal remnant after
      partial small bowel resection. AIM: The ability of an enteral diet supplemented
      with the ornithine salt: ornithine alpha ketoglutarate (OKG), a precursor for
      polyamine synthesis, to modulate the adaptive response of the remnant ileum after
      jejunectomy was evaluated. METHODS: Adult Wistar rats underwent a resection of
      the proximal 50% of the small intestine. Controls underwent a single transection.
      The rats were fed intragastrically with a nutritive mixture supplemented either
      with casein hydrolysate or with OKG (1 g/kg). The isoenergetic and
      isonitrogeneous diets was given continuously for seven days. RESULTS: Villus and
      crypt hyperplasia was observed in the remnant ileum compared with transfected
      controls. OKG supplementation started after resection a further increase in
      villus height. After resection, OKG supplementation increased significantly the
      putrescine content and the amount of ornithine decarboxylase mRNA. A twofold to
      threefold increase of sucrase activity was measured in the resected animals
      compared with the transected rats. In contrast, the amount of sucrase mRNA was
      significantly lower in the ileum of the resected rats and OKG supplementation
      initiated a further drop in the amount of sucrase mRNA without pronounced changes
      in enzyme activity. CONCLUSIONS: The adaptive hypertrophy seen after resection
      can be accelerated by supplementing the diet with ornithine (OKG) a precursor of
      polyamine synthesis. In the remnant ileum, the reduced amount of sucrase mRNA,
      despite the increased level of sucrase activity, suggests a post-translational
      control of sucrase expression.

PMID- 9155579
TI  - Increased expression of transforming growth factor beta s after acute oedematous
      pancreatitis in rats suggests a role in pancreatic repair.
AB  - BACKGROUND: Transforming growth factor beta isoforms (TGF beta s) belong to a
      family of multifunctional regulators of cellular growth and differentiation. They
      are mitogenic and chemotactic for fibroblasts and are potent stimulators of
      extracellular matrix production (collagen) and deposition. Upregulation of TGF
      beta transcription has been reported for several in vivo systems during repair
      after injury. AIMS: To study the expression of the three mammalian isoforms of
      TGF beta (TGF beta 1-3) and their relation to collagen expression as a marker for
      fibroblast response in acute oedematous pancreatitis in rats. METHODS: Using
      northern blot analysis and immunohistochemistry, the expression and localisation
      of TGF beta isoforms, collagen, and amylase were analysed during the course of
      acute oedematous pancreatitis in rats, experimentally induced by intravenous
      caerulein infusion. RESULTS: Induction of acute pancreatitis resulted in a
      biphasic peak pattern of expression of TGF beta 1, beta 2, and beta 3 mRNA, with
      a pronounced increase from day 1 to day 3 (sixfold, 2.5-fold, fivefold,
      respectively) and again from day 5 to day 7 (three-fold, 2.3-fold, 3.5-fold,
      respectively). The temporal changes in TGF beta mRNA identically paralleled the
      expression in collagen mRNA. In contrast, amylase mRNA expression, used as a
      general indicator of acinar cell integrity, was slightly decreased after
      induction of acute pancreatitis. Immunohistochemical analysis of pancreatitis
      tissue showed that increased expression of TGF beta s was mainly present in the
      pancreatic acinar and ductal cells; this was evident within one day after
      pancreatitis induction. CONCLUSION: Overexpression of TGF beta s after induction
      of acute pancreatitis suggests a role for these proteins in pancreatic repair and
      remodelling. The increased levels of TGF beta s may help suppress immune
      activation, and may contribute to the increase in the extracellular matrix
      including collagen and to the repair of the pancreatic parenchyma.

PMID- 9155580
TI  - Post-ERP pancreatitis as a model for cytokine induced acute phase response in
      acute pancreatitis.
AB  - BACKGROUND/AIMS: By contrast with animal models, in most cases it is not possible
      to examine the systemic response in patients in the first hours after onset of
      acute pancreatitis. The aim was to determine whether endoscopic retrograde
      cholangiopancreaticography (ERP)-induced pancreatitis can be used as a human
      model for the study of cytokine release and acute phase response in the first
      hours of the disease. PATIENTS AND METHODS: Seventy consecutive patients
      undergoing ERP for different reasons were prospectively evaluated by sampling
      blood before and 0, 1, 4, 12, 24, and 48 hours after ERP and, in patients who
      developed an acute post-ERP pancreatitis, daily until C reactive protein (CRP)
      was within normal range. A post-ERP pancreatitis was defined as a three-fold
      increase of amylase or lipase and at least two of the clinical symptoms:
      abdominal pain, nausea, vomiting, and peritonism during 24 hours after ERP.
      RESULTS: Nine out of 70 patients developed an acute pancreatitis. Cytokines and
      other biochemical variables were measured in those nine and in 34 patients out of
      the 61 not developing pancreatitis. In the nine patients amylase and lipase
      increased within the first hour after ERP with maximum values between four and 12
      hours. Interleukin-6 increased to maximal concentrations after 24-48 hours and
      the highest CRP concentrations were found 72 hours after ERP. Tumour necrosis
      factor did not change. CONCLUSION: Post-ERP pancreatitis is an ideal model in
      which to examine the initial cytokine and acute phase response in the first hours
      after the initiation of the disease.

PMID- 9155581
TI  - Role of endogenous nitric oxide in the control of exocrine and endocrine
      pancreatic secretion in humans.
AB  - BACKGROUND: Nitric oxide (NO) is an unstable vasodilator formed by NO synthetase
      (NOS) from L-arginine (L-Arg) in various cells but its role in the control of
      pancreatic secretion in humans has not been examined. AIMS: This study was
      designed to determine the role of endogenous NO in the control of exocrine and
      endocrine pancreas using NOS inhibitor, NG-monomethyl-L-Arg (L-NMMA). METHODS:
      Pancreatic secretion was stimulated by intravenous infusion of secretin (80
      pmol/kg/h) plus caerulein (50 pmol/kg/h) and duodenal content was aspirated by
      gastroduodenal tube. Two series of tests with secretagogue infusion were
      performed, one, with addition of graded doses of L-NMMA and, another, with
      addition of a constant dose of L-Arg alone followed by L-NMMA alone and finally
      by a combination of L-Arg and L-NMMA. RESULTS: Addition of L-NMMA in graded doses
      (2-8 mumol/kg/h) reduced dose dependently the secretin-caerulein stimulated
      pancreatic enzyme secretion without alterations in the volume flow and
      bicarbonate outputs. The addition of L-Arg to L-NMMA reversed the inhibitory
      action of L-NMMA on protein enzyme response to secretin-caerulein in these
      subjects. Secretin-caerulein infusion caused significant increase in plasma
      insulin and pancreatic polypeptide levels but without changes in plasma glucagon
      or somatostatin levels. L-NMMA alone resulted in a significant fall in plasma
      insulin and pancreatic polypeptide levels, while L-Arg added to pancreatic
      secretagogue infusion caused a significant increase of plasma insulin and
      pancreatic polypeptide levels above those attained with secretagogues alone.
      After the addition of L-Arg to L-NMMA, both plasma insulin and pancreatic
      polypeptide levels rose significantly above the levels observed with L-NMMA plus
      secretin-CCK stimulation. CONCLUSION: This study provides evidence that the
      suppression of NOS reduces pancreatic enzyme secretion and the plasma insulin and
      pancreatic polypeptide levels suggesting that endogenous NO affects both exocrine
      and endocrine pancreatic secretion in humans.

PMID- 9155582
TI  - Fibrinolysis and the biliary tree.
AB  - AIMS: To investigate the fibrinolytic activity of normal and calculous human
      bile. METHODS: Fibrinolytic properties of the biliary tract were studied in
      patients with gall bladder stones (n = 7) compared with acalculous gall bladders
      (n = 8). RESULTS: Bile plasminogen activating activity was detected in a wide
      range in both groups (calculous bile median 0.35 IU/ml; range: 0.06-6.59, versus
      normal bile 0.70 IU/ml; 0.19-3.56). There was no difference in the bile
      concentration of tissue plasminogen activator between the two groups (calculous
      bile median 21.5 ng/ml versus normal bile 9.5 ng/ml), which was present in much
      greater concentrations than urokinase (calculous bile median 0.10 ng/ml versus
      normal bile 0.36 ng/ml). Both plasminogen activators were detected in low
      concentrations in gall bladder mucosa. Plasminogen activator inhibitors-1 and 2
      were detected in bile in significantly greater concentrations in patients with
      gall bladder stones (plasminogen activator inhibitor-1: calculous bile median 15
      ng/ml versus normal bile < 2 ng/ml, plasminogen activator inhibitor-2: 157 ng/ml
      versus < 6 ng/ml, p < 0.05). CONCLUSIONS: Human bile possesses fibrinolytic
      activity and the principal plasminogen activator in bile seems to be tissue
      plasminogen activator. Plasminogen activator inhibitors were present in greater
      concentrations in stone bile and may be a factor in the pathogenesis of gall
      stone formation.

PMID- 9155583
TI  - Gene expression of group II phospholipase A2 in intestine in ulcerative colitis.
AB  - BACKGROUND: It has been suggested that phospholipase A2 (PLA2) has an essential
      role in the pathogenesis of inflammatory bowel diseases. AIMS: This study aimed
      at identifying cells in intestinal and mesenteric tissue samples that might
      express group II phospholipase A2 (PLA2-II) at the mRNA and enzyme protein levels
      in patients with ulcerative colitis. PATIENTS AND TISSUE SAMPLES: Tissue samples
      were obtained from the intestine, mesentery, skeletal muscle, and subcutaneous
      fat of six patients who underwent panproctocolectomy for severe ulcerative
      colitis. Mucosal biopsy specimens were obtained from the colon of another group
      of six patients with ulcerative colitis during routine diagnostic colonoscopies.
      Tissues from six patients without intestinal inflammatory diseases served as
      controls. METHODS: Tissue samples were studied by light microscopy,
      immunohistochemistry for PLA2-II enzyme protein, and in situ hybridisation and
      northern hybridisation for PLA2-II mRNA. RESULTS: PLA2-II mRNA and PLA2-II
      protein were detected in metaplastic Paneth cells in six patients and in the
      columnar epithelial cells of colonic mucosa in four out of six patients with
      active ulcerative colitis. Positive findings were less numerous in patients with
      mild ulcerative colitis. Only two out of six control patients had a weak positive
      signal for PLA2-II mRNA and one of these two patients had a weak positive
      immunoreaction for PLA2-II in columnar epithelial cells in the colonic mucosa.
      None of the control patients had metaplastic Paneth cells. CONCLUSIONS:
      Metaplastic Paneth cells and colonic epithelial cells synthesise PLA2-II in
      ulcerative colitis. The activity of the PLA2-II synthesis seems to be related to
      the degree of inflammation in the diseased bowel.

PMID- 9155584
TI  - Lack of effect of antineutrophil cytoplasmic antibodies associated with
      ulcerative colitis on superoxide anion production from neutrophils.
AB  - BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCAs) from patients with
      vasculitidis can induce neutrophils to release oxygen radicals in vitro. ANCAs
      with a perinuclear pattern of immunofluorescence are found in most patients with
      ulcerative colitis, but several findings are against ANCAs having a pathogenetic
      role in this disease. AIMS: To evaluate the influence of ANCAs associated with
      ulcerative colitis on the respiratory burst activity of neutrophils. PATIENTS:
      Serum samples were obtained from 14 patients with ulcerative colitis, seven of
      whom showed positivity for p-ANCAs, three patients with vasculitidis, two with
      positivity for p-ANCAs, and one for c-ANCAs, and seven healthy volunteers.
      METHODS: A positive ANCA serology was determined with a standard indirect
      immunofluorescence assay. Purified immunoglobulins (IgGs) were prepared from
      serum samples by DEAE-Affigel blue chromatography. Human neutrophils were
      prepared by dextran-Ficoll-Hypaque separation. Superoxide anion (O2-.) generation
      was measured by following the superoxide dismutase inhibitable reduction of
      ferricytochrome. RESULTS: There were no significant differences among samples
      from ulcerative colitis IgG p-ANCA positive, ulcerative colitis IgG p-ANCA
      negative patients, and controls on O2-. production, whereas ANCA positive IgG
      from vasculitidis significantly enhanced O2-. release (p < 0.001). CONCLUSIONS: p
      ANCAs associated with ulcerative colitis have no effect on the respiratory burst
      activity of normal human neutrophils in vitro. These results reinforce the
      hypotheses that ANCAs are unlikely to contribute to the pathogenesis of
      ulcerative colitis.

PMID- 9155585
TI  - Antineutrophil cytoplasm autoantibodies against bactericidal/permeability
      increasing protein in inflammatory bowel disease.
AB  - BACKGROUND: Bactericidal/permeability-increasing protein (BPI), a constituent of
      primary neutrophil granules, is a potent natural antibiotic and an antineutrophil
      cytoplasm antibody (ANCA) antigen in cases of vasculitis in which the target
      antigen is neither myeloperoxidase (MPO) nor proteinase-3 (PR3). AIM: To
      investigate BPI as a possible target antigen for ANCAs in inflammatory bowel
      disease. METHODS: ANCAs were detected by routine immunofluorescence (IIF) and
      solid phase enzyme linked immunosorbent assay (ELISA) performed for antibodies to
      the purified neutrophil granule proteins; MPO, PR3, cathepsin-G, lactoferrin, and
      BPI in serum samples from 88 patients with inflammatory bowel disease (36 with
      Crohn's disease, 52 with ulcerative colitis). Thirty patients with bacterial
      enteritis acted as controls. RESULTS: Significantly more patients with ulcerative
      colitis were ANCA positive by IIF (60%) than patients with Crohn's disease (28%)
      or infectious enteritis (23%) (p < 0.001). IgG anti-BPI antibodies were present
      in 29% of patients with ulcerative colitis, 14% of patients with Crohn's disease,
      and 23% of patients with infectious enteritis, occurring in 44% of those patients
      with inflammatory bowel disease who were ANCA positive by IIF. Antibodies to
      other ANCA antigens were rare. The presence of ANCAs was not related to either
      disease activity or extent; presence of anti-BPI antibodies was significantly
      related to both a lower serum albumin concentration (p = 0.001) and a higher
      erythrocyte sedimentation rate (p = 0.02) in patients with ulcerative colitis,
      and to colonic involvement in patients with Crohn's disease (p = 0.01).
      CONCLUSION: BPI is a significant minority target antigen for ANCAs in
      inflammatory bowel disease that seems related to colonic Crohn's disease and
      disease activity in ulcerative colitis. Anti-BPI antibodies occur in infectious
      enteritis.

PMID- 9155586
TI  - Chemical and immunological testing for faecal occult blood in screening subjects
      at risk of familial colorectal cancer.
AB  - BACKGROUND: People with a family history of colorectal cancer have an increased
      risk of the disease themselves. Many centres are advocating family history
      screening by endoscopy. AIMS: The performance of chemical and immunological
      faecal occult blood tests (Haemoccult and Hemeselect) in 212 subjects with a
      family history of colorectal cancer was assessed. RESULTS: Both Hemeselect and
      Haemoccult were positive in the only patient with colorectal cancer. Hemeselect
      was more sensitive than Haemoccult for adenomas (40% compared with 20%) (adenomas
      larger than 1 cm 75% compared with 50%). No additional abnormality was detected
      by the addition of Haemoccult or Hemeselect to 60 cm flexible sigmoidoscopy in
      screening people at lower levels of familial risk. A false positive rate of 16%
      for Hemeselect resulted in a high proportion of additional colonoscopies in this
      group. CONCLUSIONS: At present faecal occult blood tests are not sufficiently
      sensitive or specific to replace endoscopy in screening people at risk of
      familial colorectal cancer.

PMID- 9155587
TI  - T cell receptor-zeta and granzyme B expression in mononuclear cell infiltrates in
      normal colon mucosa and colon carcinoma.
AB  - BACKGROUND: Whereas the presence of a lymphoid infiltrate has been associated
      with a favourable prognosis in colorectal carcinoma, the proliferative and
      cytotoxic responses of freshly isolated tumour infiltrating lymphocytes are
      frequently impaired. In mice, tumour induced immune suppression has been
      associated with a decreased expression of the zeta-chain of the T cell receptor
      (TCR)-CD3 complex, and loss of mRNA for granzyme B. AIM: To compare the
      expression of TCR-zeta and granzyme B in lymphocytes infiltrating normal colonic
      mucosa and Duke's A and D colorectal carcinomas. SPECIMENS: Paraffin wax embedded
      normal (n = 10) and malignant colonic mucosa (seven Dukes's A, nine Dukes's D).
      METHOD: Immunohistochemistry. RESULTS: The numbers of TCR-zeta + lymphocytes
      decreased from normal mucosa to Dukes's D carcinomas. In contrast, granzyme B+
      lymphocytes were more frequent in Dukes's A carcinomas than in normal mucosa, but
      disappeared from advanced stage tumours. Granzyme B expressing cells were mainly
      CD3- (natural killer/lymphokine activated killer cells) in normal mucosa, but
      CD3+ in tumours, indicating the presence of activated cytotoxic T lymphocytes. In
      vitro culture of tumour infiltrating lymphocytes rapidly restored the expression
      of both molecules. CONCLUSION: The frequency of TCR-zeta + and granzyme B+
      lymphocytes is decreased in advanced stage colorectal carcinomas. The restoration
      of expression during in vitro stimulation suggests the presence of tumour derived
      suppressive factors in situ.

PMID- 9155588
TI  - DPC4 gene mutation in colitis associated neoplasia.
AB  - BACKGROUND: Colitis associated dysplasia and cancer often have deletions
      involving the long arm of chromosome 18q, suggesting the location of a tumour
      suppressor gene critical for their tumorigenesis. The DPC4 gene, which is
      genetically inactivated in pancreatic and other cancers, has recently been
      described. AIM: Because DPC4 is located at 18q21.1, the hypothesis that it could
      be a mutated tumour suppressor gene in colitis associated neoplasms was tested.
      PATIENTS: Advanced neoplastic lesions from six patients having chronic colitis
      were analysed for DPC4. METHODS: Individual exons of DPC4 were amplified by the
      polymerase chain reaction (PCR) and sequenced from genomic DNA of tissue
      specimens dissected by cryostat. RESULTS: DPC4 was found to have biallelic
      inactivation in one of three neoplasms shown to have allelic loss of 18q. The
      mutation had been acquired somatically in a plaque of high grade dysplasia. The
      mutation created a non-sense codon, which would cause premature termination of
      protein translation. CONCLUSION: The DPC4 gene is a target of 18q LOH events in
      colitis associated neoplasia.

PMID- 9155589
TI  - Endoscopic treatment of early oesophageal or gastric cancer.
AB  - BACKGROUND AND AIMS: Endoscopic treatment has become increasingly popular in
      recent years as an alternative to surgical treatment with the hope of offering
      superior quality of life (QOL) for the patient. The results of endoscopic
      treatment of mucosal lesions of mostly early oesophageal or gastric cancer
      performed in 145 patients (155 lesions) over the past eight years were reviewed
      from the standpoint of QOL. RESULTS: In 56 patients who underwent radical
      resection of the oesophageal mucosa, no serious complications and symptoms
      occurred, with epithelialisation completed within about a month. Patients also
      showed good results regarding dietary intake and performance status (PS), and all
      are currently alive without any sign of recurrence. One time fractionated
      endoscopic resection was carried out in about 40% of the 57 patients who
      underwent gastric mucosal resection. In these 57 patients, an artificial ulcer
      measuring 3 cm or more was formed, resulting in a favourable outcome after
      healing. An overwhelming proportion of these subjects had no symptoms and good PS
      after the treatment. CONCLUSIONS: The introduction of this method, endoscopic
      mucosal resection using a cap fitted panendoscope, is expected to permit
      additional indications for endoscopic treatment. Endoscopic Nd-YAG laser
      irradiation was applied mainly to early gastric cancer lesions (32 patients),
      usually for relative indications for endoscopic treatment. This procedure is safe
      and advantageous in that it requires no hospitalisation, permits fractionated
      irradiation, and secures good QOL.

PMID- 9155590
TI  - Association between chronic hepatitis C infection and hepatocellular carcinoma in
      a Scottish population.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in
      the world. The geographical prevalence varies considerably in different countries
      and Scotland is regarded as an area of low risk for the disease. AIMS: To assess
      the association between chronic hepatitis C infection (HCV) and HCC in a
      population of patients presenting to a single hospital. PATIENTS: One hundred and
      fourteen cases of histologically confirmed liver cancer presenting to the Royal
      Infirmary of Edinburgh between 1985 and 1994 were examined. METHODS: Of 114 cases
      of HCC, 80 samples of stored sera were available. Samples positive for HCV Ab
      were genotyped by restriction fragment length polymorphism analysis of HCV c-DNA.
      A population of 29 cirrhotic patients (diagnosed between 1985 and 1994) with
      chronic HCV infection was also genotyped. RESULTS: Chronic HCV infection was a
      major risk factor (30% of tested HCC patients) identified. HCV genotype 1b was
      predominant (16 of 20 patients). The time from HCV transmission to development of
      cancer ranged from 10 to 50 years (median 30). In the cirrhotic patient
      population, a broader distribution of genotypes was present (genotype 1a: 7;
      genotype 1b: 8; genotype 2b: 3; genotype 3a: 8 and genotype 4: 2). However, this
      population was significantly younger. (Mean (SD) 52 (14.5) years) (p = 0.0002)
      and demonstrated a significantly shorter duration of infection: range 10-40 years
      (median: 19). CONCLUSION: There is a strong association between chronic HCV
      infection, cirrhosis, and hepatocarcinogenesis in this Scottish population. The
      study was unable to distinguish whether the high prevalence of genotype 1b in the
      HCC population reflected increased oncogenicity in itself, or whether 1b was
      simply the most prevalent genotype in Scotland when these patients were infected.

PMID- 9155591
TI  - Analysis of Arg-Gly-Asp mimetics and soluble receptor of tumour necrosis factor
      as therapeutic modalities for concanavalin A induced hepatitis in mice.
AB  - BACKGROUND/AIMS: It has been shown that synthetic non-peptidic analogues of Arg
      Gly-Asp, a major cell adhesive ligand of extracellular matrix, prevented an
      increase in serum aminotransferase activity, as a manifestation of concanavalin A
      induced liver damage in mice. This study examined the effects of an Arg-Gly-Asp
      mimetic on liver histology and cytokine release in response to concanavalin A
      administration, and the efficacy of soluble receptor of tumour necrosis factor
      (TNF) alpha in preventing hepatitis in this model of liver injury. METHODS: Mice
      were pretreated with either the Arg-Gly-Asp mimetic SF-6,5 or recombinant soluble
      receptor of TNF alpha before their inoculation with 10 mg/kg concanavalin A.
      Liver enzymes, histology, and the serum values of TNF alpha and interleukin (IL)6
      were examined. RESULTS: The histopathological damage in the liver, and the
      concanavalin A induced release of TNF alpha and IL6 were significantly inhibited
      by the synthetic Arg-Gly-Asp mimetic (p < 0.001). Liver injury, manifested by the
      increase in serum aminotransferase and cytokines, as well as by histological
      manifestations of hepatic damage, was effectively prevented by pretreatment of
      the mice with the soluble TNF receptor (p < 0.001). CONCLUSIONS: This study
      confirms the efficacy of a synthetic Arg-Gly-Asp mimetic and soluble TNF receptor
      in the prevention of immune mediated liver damage in mice.

PMID- 9155593
TI  - Differential gene expression of the three natriuretic peptides and natriuretic
      peptide receptor subtypes in human liver.
AB  - BACKGROUND: Various effects of atrial natriuretic peptide (ANP) on the liver have
      been observed. However, there is limited information about the types of receptors
      for natriuretic peptides expressed by the human liver. AIM: To investigate gene
      expression of the three NP receptor types (NPR) as well as of the NP in human
      liver. METHODS: Presence of mRNA coding for all three NPR and for ANP, brain and
      C-type natriuretic peptide (BNP, CNP) was investigated by reverse transcription
      polymerase chain reaction (RT-PCR). Human liver tissues and hepatocellular
      carcinoma tissues were examined. RESULTS: Specific PCR products for all three
      NPR, namely NPR-A, B, and C, could be detected. Moreover, ANP and CNP, but not
      BNP mRNA was detectable. The concentration of ANP transcripts was up to fivefold
      higher in hepatocellular carcinoma compared with non-tumorous liver tissue of the
      same subjects. No difference in the expression of NP receptors relative to GAPDH
      mRNA of tumorous and non-tumorous tissue was observed except of slightly
      increased NPR-A transcripts. CONCLUSION: These data show that NPR transcripts are
      coexpressed with ANP and CNP mRNA in the human liver. This provides evidence for
      a local NP system in the human liver.

PMID- 9155594
TI  - Signals from lymphocytes in colon cancer.

PMID- 9155592
TI  - Acute effect of low dose theophylline on the circulatory disturbances of
      cirrhosis.
AB  - BACKGROUND: Adenosine is a potent vasoactive substance that may be responsible
      for mediating the altered haemodynamics found in patients with cirrhosis. AIM:
      The administration of oral theophylline was used to investigate the effect of
      adenosine receptor antagonism upon the circulation of patients with cirrhosis.
      METHODS: Twenty eight patients were given oral theophylline and intravascular
      haemodynamic measurements obtained over approximately one hour. RESULTS: After
      240 mg of oral theophylline elixir the hepatic venous pressure gradient mean fell
      from 21.8 (2.1) to 19.9 (2.4) mm Hg (p < 0.01), and azygos blood flow fell from
      481 (94) to 375 (83) ml/min (p < 0.05). There were no changes in cardiac output
      or systemic vascular resistance despite a fall in mean arterial pressure (92.2
      (2.0) to 89.2 (1.8) mm Hg; p < 0.05) and a rise in heart rate (78.3 (3.0) to 82.4
      (3.2); p < 0.001). Left renal vein flow measured by a reverse thermodilution
      catheter rose from 387 (91) to 601 (119) ml/ min (p < 0.05). The proportion of
      cardiac output perfusing the left kidney rose from 5.0 (1.3) to 9.7 (2.8)%.
      CONCLUSIONS: These changes indicate a significant role for adenosine in the renal
      vasoconstriction and a more minor role in the maintenance of portal hypertension.

PMID- 9155595
TI  - Gastric acid secretion.

PMID- 9155596
TI  - Helicobacter pylori and duodenal ulcers.

PMID- 9155597
TI  - Ultrasound for gastroenterologists.

PMID- 9155598
TI  - Peptide YY and electrolyte homeostasis.

PMID- 9155599
TI  - The United Kingdom Heart Valve Registry: the first 10 years.

PMID- 9155600
TI  - Non-invasive assessment of endothelial function.

PMID- 9155601
TI  - Treatment of primary pulmonary hypertension with continuous intravenous
      prostacyclin.
AB  - Our ultimate goal in treating patients is to improve their quality of life and to
      increase survival. The optimal treatment for primary pulmonary hypertension will
      continue to change as our understanding of its causes improves and as progress is
      made in lung transplantation. There is no one best treatment for all patients.
      Optimal medical and surgical treatment must be tailored to the individual with
      changes in therapeutic regimens based on serial evaluations. Quality of life and
      survival have improved with current treatments and the future should offer
      additional therapies-inhaled nitric oxide, endothelin receptor blockers, and
      other modulators of the pulmonary vascular bed-to improve further the treatment
      of this disease. In conclusion, although primary pulmonary hypertension, if
      untreated, is most often a rapidly progressive and fatal disease, recent advances
      in the treatment have significantly improved the outcome for patients. Although
      transplantation is often considered the only definitive treatment for patients
      with primary pulmonary hypertension, medical treatment seems to be an effective
      long term palliation to successful transplantation as well as a possible
      alternative treatment to transplantation in selected children and adults. Quality
      of life and cost analyses, as well as longer follow up studies are needed to
      determine the best treatment for patients with primary pulmonary hypertension.

PMID- 9155602
TI  - Ferdinand Sauerbruch (1875-1951).

PMID- 9155603
TI  - Less invasive coronary artery bypass grafting: without cardiopulmonary bypass and
      via reduced surgical access.

PMID- 9155604
TI  - Minimal access surgery.

PMID- 9155605
TI  - Aneurysm of the left coronary artery bifurcation.

PMID- 9155606
TI  - Minimal access coronary artery surgery.

PMID- 9155607
TI  - Heart failure and atrial fibrillation: current concepts and controversies.
AB  - Heart failure and atrial fibrillation are very common, particularly in the
      elderly. Owing to common risk factors both disorders are often present in the
      same patient. In addition, there is increasing evidence of a complex, reciprocal
      relation between heart failure and atrial fibrillation. Thus heart failure may
      cause atrial fibrillation, with electromechanical feedback and neurohumoral
      activation playing an important mediating role. In addition, atrial fibrillation
      may promote heart failure; in particular, when there is an uncontrolled
      ventricular rate, tachycardiomyopathy may develop and thereby heart failure.
      Eventually, a vicious circle between heart failure and atrial fibrillation may
      form, in which neurohumoral activation and subtle derangement of rate control are
      involved. Treatment should aim at unloading of the heart, adequate control of
      ventricular rate, and correction of neurohumoral activation. Angiotensin
      converting enzyme inhibitors may help to achieve these goals. Treatment should
      also include an attempt to restore sinus rhythm through electrical cardioversion,
      though appropriate timing of cardioversion is difficult. His bundle ablation may
      be used to achieve adequate rate control in drug refractory cases.

PMID- 9155608
TI  - Ischaemic preconditioning reduces troponin T release in patients undergoing
      coronary artery bypass surgery.
AB  - OBJECTIVE: To investigate whether ischaemic preconditioning could reduce
      myocardial injury, as manifest by troponin T release, in patients undergoing
      elective coronary artery bypass surgery. DESIGN: Randomised controlled trial.
      SETTING: Cardiothoracic unit of a tertiary care centre. PATIENTS: Patients with
      three vessel coronary artery disease and stable angina admitted for first time
      elective coronary artery bypass surgery were invited to take part in the study;
      33 patients were randomised into control or preconditioning groups. INTERVENTION:
      Patients in the preconditioning group were exposed to two additional three minute
      periods of myocardial ischaemia at the beginning of the revascularisation
      operation, before the ischaemic period used for the first coronary artery bypass
      graft distal anastomosis. MAIN OUTCOME MEASURE: Serum troponin T concentration at
      72 hours after cardiopulmonary bypass. RESULTS: The troponin T assays were
      performed by blinded observers at a different hospital. All patients had
      undetectable serum troponin T (< 0.1 microgram/l) before cardiopulmonary bypass,
      and troponin T was raised postoperatively in all patients. At 72 hours, serum
      troponin T was lower (P = 0.05) in the preconditioned group (median 0.3
      microgram/l) than in the control group (median 1.4 micrograms/l). CONCLUSIONS:
      The direct application of a preconditioning stimulus in clinical practice has
      been shown, for the first time, to protect patients against irreversible myocyte
      injury.

PMID- 9155609
TI  - Poor clinical performance of the Wessex porcine heart valve bioprosthesis at nine
      years' follow up.
AB  - OBJECTIVE: To assess the long term performance of the Wessex porcine
      bioprostheses implanted in a consecutive series of patients. DESIGN: A
      retrospective case series. PATIENTS: Between January 1985 and July 1991, 184
      Wessex bioprostheses (78 mitral, 102 aortic, and 4 tricuspid) were implanted in
      150 patients. The patients were 55% (83/150) male and 45% (67/150) female; mean
      age was 60 (SD 10) years. RESULTS: Hospital mortality was 9.3% (14/150). Total
      follow up was 696 patient-years (mean 4.7 years per patient). Linearised rates
      (events per 100 patient-years (SEM) for postoperative complications for patients
      with isolated mitral valve replacement, isolated aortic valve replacement, and
      multiple valve replacement were, respectively: late mortality: 4.7 (1.6), 3.3
      (0.9), and 4.9 (1.9); thromboembolism: 5.8 (1.8), 3.0 (0.9), and 2.8 (1.4); valve
      thrombosis: 1.0 (0.7), 0.3 (0.3), and 0.7 (0.7); structural failure: 5.8 (1.7),
      1.9 (0.7), and 7.1 (2.2). Actuarial freedom from complications at nine years (70%
      confidence interval) was: late mortality: 61 (9)%, 57 (13)%, and 59 (12)%;
      thromboembolism and valve thrombosis: 71 (9)%, 79 (6)%, and 81 (8)%; structural
      failure: 33 (14)%, 50 (16)%, and 12 (14)%; all valve related morbidity/mortality:
      31 (10)%, 21 (11)%, and 7 (9)%. Stent fractures appeared in 11 of 17 explanted
      prostheses; actuarial freedom from stent fracture at nine years was 66 (12)%.
      CONCLUSIONS: The Wessex bioprosthesis is associated with high thrombogenicity,
      early structural dysfunction, and a high valve related morbidity/mortality which
      justifies very close follow up of patients fitted with them.

PMID- 9155611
TI  - Prioritising the cardiac surgery waiting list: the angina patient's perspective.
AB  - OBJECTIVE: To determine patients' views on how clinical and demographic factors
      should affect priorities for cardiac revascularisation. DESIGN: A descriptive
      survey of patients' views conducted immediately after angiography and treatment
      counselling. SUBJECTS: 136 patients who were awaiting coronary angioplasty in
      either of the two regional cardiology centres in Northern Ireland. RESULTS: About
      half the subjects (52%) felt that certain social factors such as having dependent
      relatives should be taken into account when deciding priority for surgery. A
      sizeable minority felt that younger subjects and non-smokers (40% and 44%,
      respectively) should be accorded higher priority, with older subjects and smokers
      being more likely to hold such views. CONCLUSIONS: While there is little evidence
      that demographic and lifestyle factors affect the relative efficacy of surgery,
      the challenge remains to devise a prioritisation guideline that can properly
      reflect societal values and the evidence base.

PMID- 9155610
TI  - Attenuation or absence of circadian and seasonal rhythms of acute myocardial
      infarction.
AB  - OBJECTIVES: To examine the circadian, seasonal, and weekly rhythms of acute
      myocardial infarction, and to identify subgroups in whom the rhythms are
      attenuated or absent to provide further information about the mechanisms of the
      rhythms and the processes responsible for triggering plaque events. DESIGN AND
      SETTING: Prospective, observational study in a general hospital. PATIENTS AND
      METHODS: 1225 consecutive patients admitted to a coronary care unit with acute
      myocardial infarction were studied. Admission rates were calculated according to
      the hour of the day (circadian rhythm), day of the week (weekly rhythm), and
      month of year (seasonal rhythm). The data were analysed for variations within the
      whole group and within subgroups. RESULTS: A weekly rhythm of acute myocardial
      infarction could not be demonstrated but there was a trend towards higher
      admission rates at the beginning of the week. However, the time of onset of
      symptoms showed significant circadian variation for the group as a whole, peaking
      in the morning (P = 0.006), against an otherwise fairly constant background rate.
      Subgroup analysis showed complete absence of the circadian rhythm in patients who
      were diabetic, South Asian, or taking beta blockers or aspirin on admission.
      Significant seasonal variation in admission rates was also demonstrated for the
      group as a whole with a winter peak and a summer trough (P = 0.009). Again, no
      seasonal rhythm could be demonstrated in patients who were diabetic, South Asian,
      or taking beta blockers or aspirin on admission. CONCLUSIONS: The absence of
      circadian and seasonal rhythms of acute myocardial infarction in almost identical
      subgroups suggests that common mechanisms are involved in driving these rhythms.
      The autonomic nervous system is a likely candidate because the rhythms were
      absent in patients taking beta blockers as well as in patients in whom
      derangement of autonomic function commonly occurs.

PMID- 9155612
TI  - Aspirin protects low density lipoprotein from oxidative modification.
AB  - OBJECTIVE: To examine the effects of aspirin on the potential for oxidative
      modification of low density lipoprotein (LDL). DESIGN: Before and after trial.
      SETTING: University department of medicine within a district general hospital
      campus. PATIENTS: Ten healthy normolipidaemic volunteers drawn from laboratory
      and medical staff. INTERVENTIONS: Aspirin (enteric coated) 300 mg daily for two
      weeks. MAIN OUTCOME MEASURES: In vitro oxidation of LDL following ultraviolet C
      (UVC) irradiation with measurements made of malondialdehyde, conjugated dienes,
      and electrophoretic mobility. RESULTS: There was a significant decrease in
      malondialdehyde production from LDL modified by aspirin in vivo following
      exposure to UVC irradiation for 90 minutes, culminating in a 30% decrease by 240
      minutes (mean (SD) 64.2 (9.12) v 89.6 (11.6) nmol/mg LDL protein, P = 0.029).
      These observations were borne out using LDL modified by aspirin in vitro. The UVC
      induced increase in relative electrophoretic mobility of LDL was also
      significantly reduced following aspirin treatment (mean (SD) 2.17 (0.16) v 2.66
      (0.24), P = 0.012). CONCLUSIONS: Aspirin, both in vivo and in vitro, protects LDL
      against subsequent oxidative modification, providing an additional mechanism
      whereby aspirin may protect against atherosclerosis.

PMID- 9155613
TI  - Effects of acute coronary occlusion and previous ischaemic injury on left
      ventricular wall motion in humans.
AB  - OBJECTIVE: To assess the acute effects of single and repeated coronary artery
      occlusions, during percutaneous transluminal coronary angioplasty (PTCA), on left
      ventricular long axis function in patients with stable and unstable angina.
      DESIGN: Prospective examination of ventricular systolic and diastolic long axis
      function using M mode echocardiography and transmitral Doppler in patients with
      significant coronary artery stenosis and either stable or unstable angina, during
      routine PTCA. SETTING: A tertiary referral centre for heart disease with cardiac
      catheterisation and echocardiographic facilities. SUBJECTS: 36 patients, age (SD)
      60 (8) years, with significant coronary artery disease undergoing PTCA (mean
      duration 100-130 seconds) to the left anterior descending coronary artery (LAD)
      in 18 patients, native LAD or its vein graft in eight, and right coronary artery
      in 10. Controls were 21 normal subjects, age 58 (11) years. RESULTS-AT BASELINE:
      in systole, total long axis excursion was reduced at septal, posterior, and right
      sites in patients with LAD disease, at right site in those with vein grafts, and
      at septal and right sites in patients with right coronary artery disease. Peak
      shortening rate was often reduced in all patients and onset of shortening delayed
      with respect to the Q wave in patients with LAD disease. In diastole, onset of
      lengthening was always delayed, peak lengthening rate reduced, and relative A
      wave amplitude increased in all patients. There was a consistent abnormal
      shortening of the long axis during the isovolumic relaxation period in the 14
      patients with unstable angina, not seen in the others. Transmitral A wave
      velocity was also increased and the onset of E wave delayed with respect to A2.
      At first balloon inflation: the extent of pre-existing systolic and particularly
      diastolic abnormalities consistently increased in patients with LAD or right
      coronary artery occlusion. This was associated with further delay in the onset of
      the transmitral Doppler E wave as its peak velocity fell and E/A ratio increased.
      In unstable angina, balloon inflation caused minor changes only in systolic
      function and no change in diastolic function. At second balloon inflation:
      systolic changes were the same as with the first inflation, while diastolic
      changes were attenuated by 10-15%. CONCLUSIONS: In stable angina intracoronary
      balloon inflation aggravated pre-existing systolic and diastolic abnormalities in
      the territory of the occluded vessel, indicating the dependence of both on
      coronary flow. In unstable angina balloon inflation caused only minor
      deterioration in systolic function, and diastolic changes-including the
      characteristic abnormal shortening during isovolumic relaxation-were unaffected.
      Thus resting abnormalities of left ventricular function in unstable angina are
      effectively dissociated from acute changes in coronary flow. Overall, the
      severity of systolic disturbances was unaltered by a second balloon inflation,
      but diastolic disturbances were attenuated by 10-15%, compatible with ischaemic
      preconditioning or recruitment of collaterals.

PMID- 9155614
TI  - Prognostic significance of right ventricular afterload stress detected by
      echocardiography in patients with clinically suspected pulmonary embolism.
AB  - OBJECTIVE: To investigate the prognostic value of echocardiographic findings in
      patients who present with symptoms suggestive of acute pulmonary embolism.
      DESIGN: 317 patients with clinically suspected pulmonary embolism were
      prospectively evaluated by echocardiography for the presence of right ventricular
      afterload stress and right heart or pulmonary artery thrombi. Objective
      confirmation of pulmonary embolism by lung scan or pulmonary angiography was
      obtained in 164 (52%). The presence of deep venous thrombosis was established in
      90 of 158 patients (57%) who underwent phlebographic or Doppler sonographic
      studies. RESULTS: Right ventricular afterload stress was diagnosed in 87 patients
      (27%). Objective confirmation of pulmonary embolism and diagnosis of deep venous
      thrombosis was more common in patients with right ventricular afterload stress
      than in those without (83% v 40% and 46% v 22%, respectively; P < 0.001). This
      was also true for the detection of thrombi in the right heart and major pulmonary
      arteries (12 patients v 1 patient; P < 0.001) as well as for the in-hospital
      mortality from venous thromboembolism (13% v 0.9%; P < 0.001). One year mortality
      from pulmonary embolism was 13% in patients with right ventricular afterload
      stress at presentation compared with 1.3% in those without (P < 0.001).
      CONCLUSIONS: The presence of right ventricular afterload stress detected by
      echocardiography is a major determinant of short term prognosis in patients with
      clinically suspected acute pulmonary embolism.

PMID- 9155615
TI  - Cutting balloon angioplasty and stenting for aorto-ostial lesions.
AB  - OBJECTIVE: To investigate the use of a cutting balloon to overcome aorto-ostial
      lesions before stent implantation and thereby reduce the restenosis rate. DESIGN:
      Observational follow up study. SETTING: Tertiary referral centre. PATIENTS: Eight
      patients (two female, six male) aged 58.2 (SD 10.1) years with Canadian
      Cardiovascular Society (CCS) grade II-IV angina were recruited. They each had a
      single target lesion (three in native coronaries, five in vein grafts).
      INTERVENTION AND RESULTS: After high pressure angioplasty (18 (3.8) bar), there
      was only a small reduction in the luminal stenosis, from 82 (9)% to 68 (10)%, as
      assessed by on line quantitative coronary angiography. However, using the cutting
      balloon there was a marked reduction in the luminal stenosis to 44 (15)%,
      facilitating stent insertion. Subsequent high pressure dilatation resulted in a
      final stenosis of 10 (7)%. At 6 (2) months' follow up the marked symptomatic
      improvement, to CCS angina grade 0-II, was maintained and there were no further
      cardiac events or interventions. CONCLUSION: Cutting balloon angioplasty followed
      by stent insertion is a feasible technique for the treatment of aorto-ostial
      lesions, meriting further investigation.

PMID- 9155616
TI  - Vascular remodelling in intramyocardial resistance vessels in hypertensive human
      cardiac transplant recipients.
AB  - OBJECTIVE: Cardiac transplant recipients often develop hypertension as a side
      effect of immunosuppressive treatment. The aim of this study was to use the
      serial endomyocardial biopsies taken to monitor rejection to study the early and
      sequential arterial changes in human myocardial resistance arteries as
      hypertension develops. METHODS: At least 14 biopsies were studied from each of 23
      patients, divided into a normotensive group (12 patients with a diastolic
      pressure never greater than 90 mm Hg) and a hypertensive group (11 patients with
      more than 10% of diastolic pressure measurements above 100 mm Hg). Morphometric
      analysis of between 30 and 50 arteries and arterioles in two widely separated
      histological levels from each biopsy was undertaken using an Optomax image
      analyser. RESULTS: There was a correlation between blood pressure, particularly
      diastolic pressure, and rate of medial thickening of intramyocardial coronary
      resistance arteries and arterioles (P = 0.0025). There was also a correlation
      between serum cyclosporin A concentrations and mean artery wall thickness (P =
      0.003). CONCLUSIONS: Hypertension and cyclosporin A treatment are associated with
      significant wall thickening of intramyocardial resistance vessels in cardiac
      allograft recipients. These changes may be functionally and clinically important.

PMID- 9155617
TI  - Impact of continuous quality improvement on selection of pacing mode and rate of
      complications in permanent pacing.
AB  - OBJECTIVE: To improve pacing mode selection and to reduce complications of pacing
      using continuous quality improvement. DESIGN: Criterion standard study.
      Comparison of implantations from 1992-94 with preset standards. Implementation of
      corrections in 1994 and re-evaluation in 1995, with one year follow up of all
      patients. SETTING: Tertiary hospital. PATIENTS: Consecutive patients implanted
      with a pacemaker from January 1992 to October 1993, 361 patients; October 1993 to
      June 1994, 115 patients; and January 1995 to October 1995, 140 patients. MAIN
      OUTCOME MEASURES: Reasons for not choosing physiological pacing and complications
      of pacemaker implantation. RESULTS: Most frequent reasons for not selecting
      physiological pacing for patients in sinus node disease were age (12.8%, 5 of 39)
      and technical problems (12.8%, 5 of 39); and for patients in atrioventricular
      block, age (31.4%, 16 of 51), and disability due to other diseases (13.7%, 7 of
      51). To improve the standards, age as a sole reason for not selecting
      physiological pacing was disregarded and VDD pacing was introduced. Follow up
      showed fulfillment of standards. Cost analysis indicated minimally increased
      expenses of pacing hardware and no additional costs of procedures. A high rate of
      complications (16.2%, 77 of 476) was found related to atrial lead displacement
      (10.2%, 19 of 186), and to subclavian puncture from January 92-June 94. To reduce
      complications use of atrial screw-in leads and cephalic cut down were encouraged.
      Follow up showed significant reduction of complications from January 92-June 94
      (77 of 476) compared with January 95-October 95 (12 of 140) (P = 0.03).
      CONCLUSIONS: Better compliance with international pacing guidelines was obtained
      by registration of reasons for deviations followed by corrections of procedures.
      By using screw-in leads and by using cephalic cut down the set standards were
      met.

PMID- 9155619
TI  - Absence of mutations in the regulatory domain of the gap junction protein
      connexin 43 in patients with visceroatrial heterotaxy.
AB  - OBJECTIVE: To determine the frequency of mutations in the regulatory domain of
      the gap junction protein connexin 43 in patients with visceroatrial heterotaxy.
      DESIGN: Mutation screening of the terminal 200 base pairs of connexin43 gene
      coding sequence in a series of patients from tertiary care centres. PATIENTS: 48
      patients with visceroatrial heterotaxy attending UK Regional Paediatric
      Cardiology Centres. RESULTS: No changes from the published connexin43 consensus
      sequence were found in any of the 48 patients studied. CONCLUSIONS: Germline
      mutations of the phosphorylation sites in teh regulatory domain of the connexin43
      gene are rare in patients with visceroatrial heterotaxy.

PMID- 9155618
TI  - Radiofrequency catheter ablation of accessory atrioventricular pathways: primary
      failure and recurrence of conduction.
AB  - OBJECTIVE: To identify possible factors associated with primary failure of
      radiofrequency ablation of accessory pathways or recurrence of accessory pathway
      conduction. PATIENTS AND METHODS: Radiofrequency ablation of accessory pathways
      failed in 25 of 243 patients, and recurrence of accessory pathway conduction
      occurred in an additional 13 patients. Factors possibly related to primary
      failure and recurrence were analysed. RESULTS: Primary failure and recurrence
      were less frequent in patients with left sided pathways (7% v 19%; 4% v 24%; P =
      0.04). The factors that might relate to primary failure included an unstable
      catheter position (seven patients), a possible epicardial pathway (six patients),
      or misdiagnosis of accessory pathway location (two patients). The major factors
      for recurrence included the stability of the local atrial electrogram < or = 0.5
      together with the stability of the local ventricular electrogram < or = 0.8, and
      prolonged time to pathway conduction block > or = 12 seconds). Thirty one
      patients underwent repeat ablation which was successful in 28. CONCLUSIONS:
      Primary failure and recurrence were more frequent in patients with right sided
      pathways. An unstable catheter position and a possible epicardial pathway
      location are the main contributing factors for primary failure, while unstable
      local electrograms and prolonged time to block are independent predictors for
      recurrence.

PMID- 9155620
TI  - Sex and coronary heart disease: the relative probability of dying in hospital.

PMID- 9155621
TI  - Ventricular tachycardia initiated by high energy cardioversion in a patient with
      an implantable cardioverter defibrillator.
AB  - A transvenous implantable cardioverter defibrillator (ICD) was implanted into a
      58 year old woman with idiopathic dilated cardiomyopathy who had drug refractory
      monomorphic ventricular tachycardia (VT). Antitachycardia pacing failed to
      terminate the VT; termination was attempted at 24 J, which was above the
      defibrillation threshold. When cardioversion at 24 J was delivered, VT with a
      different morphology and slower rate was reproducibly initiated. At 3 J, however,
      the original VT was successfully terminated without initiation of the slower VT.
      A new VT may be induced by high energy cardioversion. This may be a manifestation
      of the proarrhythmic potential of ICDs.

PMID- 9155622
TI  - QT interval dynamics and heart rate variability preceding a case of cardiac
      arrest.
AB  - A 71 year old man with hypertensive heart disease and chronic renal failure was
      wearing a Holter monitor when he had a cardiac arrest. He had ventricular
      fibrillation (VF) and died despite prompt resuscitation. In the 15 minutes
      preceding the VF there was a sudden increase in heart rate, followed by a brief
      period of atrial fibrillation leading to ventricular tachycardia, which in turn
      rapidly degenerated into VF. The QT interval and heart rate variability were
      studied half hourly over the seven hours preceding the cardiac arrest, using a
      computerised Holter system. A further detailed analysis was performed over the
      final hour before the cardiac arrest. An abrupt increase in the steepness of the
      QT/RR slope, a prolonged QTc, and a reduction in the heart rate variability were
      observed in the interval that immediately preceded the onset of the terminal
      rhythm disturbance.

PMID- 9155623
TI  - Cardiac echinococcosis--a rare echocardiographic diagnosis.
AB  - A 30 year old female admitted for evaluation of left chest pain was suspected to
      have multiple cardiac hydatid cysts. The diagnosis was established by cross
      sectional echocardiography and computed tomography, supported by enzyme linked
      immunosorbent assay (ELISA) for echinococcosis. Medical therapy altered the
      echopattern of the cysts but failed to reduce cystic masses. Surgery was
      advocated but refused by the patient.

PMID- 9155625
TI  - Erratic prolongation of the pacing spike interval with presyncope as the only
      manifestation of minute bipolar lead insulation failure.

PMID- 9155626
TI  - Chemodectoma in a patient with a single ventricle.

PMID- 9155624
TI  - Listeria endocarditis: current management and patient outcome--world literature
      review.
AB  - This is believed to be the 58th reported case of Listeria monocytogenes infective
      endocarditis. Published reports worldwide were reviewed as to treatment, outcome,
      and prognostic features. There is controversy over whether all patients with this
      condition should have surgery. Moreover the best antibiotic treatment is not
      known, which accounts for the heterogeneity of regimens used. Listeria
      endocarditis has a high mortality rate (37%). This was higher in men (41% v 32%)
      and in patients with valve prostheses (41% v 31%), though neither observation
      reached statistical significance. There was no significant difference in
      mortality between surgical and non-surgical treatment, but untreated listeria
      endocarditis proved universally fatal. From the data, treatment with ampicillin
      is recommended, with resort to surgery in cases where the infection cannot be
      eradicated or where haemodynamic compromise has occurred.

PMID- 9155627
TI  - Inappropriate shocks in a patient treated with a cardioverter defibrillator.

PMID- 9155628
TI  - Multiple cardiac rhabdomyomas: tuberous sclerosis or not?

PMID- 9155629
TI  - Coronary patients need cardiologists.

PMID- 9155630
TI  - Hyperhomocysteinaemia and premature coronary artery disease in the Chinese.

PMID- 9155631
TI  - Homocysteinaemia and coronary atherosclerosis.

PMID- 9155632
TI  - Hypereosinophilic syndrome: endomyocardial fibrosis.

PMID- 9155633
TI  - Endomyocardial fibrosis in Egypt: an illustrated review.

PMID- 9155634
TI  - Deterioration in renal function with enalapril but not losartan in a patient with
      renal artery stenosis in a solitary kidney.

PMID- 9155635
TI  - Stability of plasma concentrations of N- and C-terminal atrial natriuretic
      peptides at room temperature.

PMID- 9155636
TI  - Intranasal antigen targeting to MHC class II molecules primes local IgA and serum
      IgG antibody responses in mice.
AB  - Covalent conjugates of hen egg lysozyme (HEL) and anti-major histocompatibility
      complex (MHC) class II monoclonal antibodies (mAb) were used to immunize mice
      intranasally. Three weeks after intranasal (IN) priming, mice responded rapidly
      to IN challenge with a mixture of HEL and cholera toxin (CT), by producing large
      titres of anti-HEL IgA and IgG1 antibody in serum, and IgA antibody in nasal
      secretions. No secondary response to HEL plus CT occurred in mice that received
      no priming or mice primed with HEL alone. The secondary serum IgG antibody
      response was dominated by the IgG1 subclass. HEL combined with CT adjuvant worked
      much better than HEL alone in producing the secondary response. Control
      conjugates, containing an IgG isotype-matched mAb without specificity for mouse
      tissues, provided poor priming. Mice expressing MHC class II molecules, to which
      the anti-MHC II mAb could not bind, produced a weak antibody response compared
      with those that expressed the appropriate. MHC class II molecule. Our results
      demonstrate that immunotargeting to MHC class II molecules via the IN route
      allows priming of the local IgA and circulating IgG antibody, and indicate that
      this technique is a feasible approach for delivery of subunit vaccines in the
      upper respiratory tract.

PMID- 9155637
TI  - Membrane isoforms of human immunoglobulins of the A1 and A2 isotypes: structural
      and functional study.
AB  - As for IgM, human IgA occurs either as soluble molecules in plasma and various
      other body fluids, or as membrane-bound molecules on differentiated B cells,
      where they are part of the B-cell receptor for antigen (BCR). We studied the
      structure of transcripts encoding the membrane-anchored alpha-chain of the human
      BCR alpha, which may be present in two different forms resulting from alternate
      splicing of the alpha-chain mRNA (type I or type II). The ratio of type I versus
      type II did not vary upon stimulation of a B-cell line with various cytokines.
      Rather, it differed strikingly in cells expressing either the IgA1 or IgA2
      isotype of the BCR alpha, with virtually no type II alpha-chain in the latter. Co
      modulation experiments also yielded different results for both isotypes, since
      they demonstrated a physical association of both membrane (m)IgA1 and mIgA2 with
      CD79b, the beta component of the BCR Ig alpha/Ig beta heterodimer, but only of
      mIgA1 with CD19. Whatever the isotype, the BCR of the IgA class was able to carry
      out signal transduction upon cross-linking by specific monoclonal antibodies but,
      in contrast to mIgM, it relied mainly on the entry of extracellular Ca2+ rather
      than on the release of intracellular stocks.

PMID- 9155638
TI  - Increased adjuvant efficacy in stimulation of antibody responses after macrophage
      elimination in vivo.
AB  - To investigate whether macrophages influence the efficacy of adjuvants, we
      locally eliminated lymph node macrophages with dichloromethylene diphosphonate
      containing-liposomes before primary immunization. After macrophage elimination,
      animals were immunized with a soluble antigen (TNP-KLH; 2,4,6-trinitrophenyl
      keyhole limpet haemocyanin) either in phosphate-buffered saline (PBS), in
      complete Freund's adjuvant (CFA), or in Specol is a water-in-oil emulsion,
      considered to be less aggressive than CFA, but equally effective. A secondary
      immunization followed with TNP-KLH. In vivo macrophage elimination before
      Specol/TNP-KLH immunization resulted in increased adjuvant efficacy as measured
      by (primary) antibody responses. This suggests that the activity of Specol is not
      primarily mediated through macrophages but rather through other antigen
      presenting cell types (e.g. dendritic cells, B cells, fibroblasts). The overall
      quality of produced antibodies, in terms of isotype distribution and affinity
      maturation, remained the same. After primary injection, CFA/TNP-KLH immunization
      resulted in significantly higher antibody responses in macrophage-depleted
      animals and antibody responses did not increase significantly after secondary
      immunization. However, a booster effect was found when macrophages were not
      eliminated before CFA/TNP-KLH immunization, suggesting that the presence of
      macrophages during the first weeks of the primary immune response is essential
      for the induction of an effective secondary response in CFA immunizations. In
      conclusion, macrophage depletion before immunization with a soluble T-cell
      dependent antigen combined with Specol may enhance specific antibody responses
      without changing the isotype or affinity of the antibodies.

PMID- 9155639
TI  - Modulation of immune dysfunction during murine leukaemia retrovirus infection of
      old mice by dehydroepiandrosterone sulphate (DHEAS).
AB  - Ageing, leukaemia and acquired immune deficiency syndrome (AIDS) are conditions
      with dysregulated cytokine production. As dehydroepiandrosterone sulphate (DHEAS)
      restored normal cytokine production in old mice its effects on retrovirally
      infected old mice were investigated. Retrovirus infection and ageing-induced
      immune dysfunction. Murine retrovirus-infected old C57BL/6 female mice consumed
      0.22 or 0.44 microgram of DHEAS/mouse/day beginning 2 weeks postinfection for 10
      weeks. DHEAS largely prevented the retrovirus-induced reduction in T-cell and B
      cell mitogenesis. DHEAS supplement prevented loss of cytokines [interleukin-2 (IL
      2) and interferon-gamma] secretion by mitogen-stimulated splenocytes representing
      T helper 1 (Th1) cell phenotypes. It also suppressed the retrovirus-induced,
      excessive production of cytokines (IL-6 and IL-10) by Th2 cells. The highest dose
      of DHEAS reduced IL-6 production by splenocytes from uninfected old mice by 75%
      while increasing their IL-2 secretion by nearly 50%. Thus immune dysfunction
      induced by ageing, even when exacerbated by murine retrovirus infection, was
      largely prevented by DHEAS.

PMID- 9155640
TI  - Involvement of Stat3 in interleukin-6-induced IgM production in a human B-cell
      line.
AB  - Interleukin-6 (IL-6) is an important B-cell growth and differentiation factor. IL
      6 treatment of the human lymphoblastoid cell line, SKW6.4, leads to increased IgM
      production. We have previously shown that IL-6 induces activation of JAK1 and
      JAK2 in human B cell lines. A chimeric IL-6 receptor, comprised of the
      intracellular tail of the IL-6 receptor subunit gp130 fused to the extracellular
      domain of the epidermal growth factor (EGF) receptor, was stably transfected into
      SKW6.4 cells. EGF treatment induced IgM production in cells transfected with an
      intact gp130 cytoplasmic tail, but not in untransfected cells or cells
      transfected with a cytoplasmic tail lacking all four signal transducers and
      activators of transcription (Stat) binding sites. Moreover, EGF treatment induced
      Stat3 phosphorylation in cells transfected with the intact chimeric EGF-gp130
      receptor along with induction of DNA-mobility shift of a classical interferon
      gamma-activated site. To define further the relation between Stat3 activation and
      enhanced IgM production, we determined the effect of chimeric gp130 on the
      transcriptional activation of a genetic element linked to immunoglobulin
      production, namely the immunoglobulin heavy chain enhancer (IgH-enhancer).
      Parental as well as transfected SKW6.4 cells were transiently transfected with an
      IgH-enhancer-luciferase construct. The transcriptional activity of the IgH
      luciferase construct was induced upon ligation of the full-length chimeric
      receptor but not by truncated gp130 receptors. Moreover, the gp130-induced
      activity of this reporter gene was abrogated by Stat3EE, a mutant Stat3 incapable
      of binding DNA. These results indicate that IL-6-induced B-cell differentiation,
      as measured by IgM production, may be controlled by Stat3 proteins.

PMID- 9155641
TI  - Tumour necrosis factor-alpha up-regulates decay-accelerating factor gene
      expression in human intestinal epithelial cells.
AB  - The increased expression of decay-accelerating factor (DAF) has been detected in
      intestinal epithelial cells at the inflamed mucosa. In this study, we examined
      the effects of tumour necrosis factor (TNF)-alpha on DAF expression in three
      intestinal epithelial cell lines. DAF mRNA expression was evaluated by Northern
      blot analysis, and DAF protein expression was analysed by biotin labelling and
      immunoprecipitation. TNF-alpha induced a marked increase in DAF mRNA and protein
      expression in HT-29, T84 and Caco-2 cells. In HT-29 cells, the effects of TNF-a
      on DAF mRNA accumulation were observed in a dose-dependent manner; DAF mRNA
      accumulation reached a maximum at 3-6 hr, and then gradually decreased. These
      effects of TNF-alpha required de novo protein synthesis. Messenger RNA stability
      studies suggested that TNF-alpha partially regulated DAF gene expression by a
      posttranscriptional mechanism. Moreover, the combination of TNF-alpha and
      interleukin (IL)-4 induced an additive increase in DAF mRNA accumulation in HT-29
      and T84 cells. In human intestinal epithelial cells, TNF-alpha acts as a potent
      inducer of DAF mRNA expression, indicating an important role for TNF-alpha in the
      regulation of DAF expression at the inflamed mucosa.

PMID- 9155642
TI  - Nitric oxide increased interleukin-4 expression in T lymphocytes.
AB  - Nitric oxide (NO) is a regulator of many biological functions including T helper
      1 (Th1)/T helper 2 cells balance. It has been demonstrated that NO inhibits the
      secretion of interleukin-2 (IL-2) and interferon-gamma on Th1 cells. Here we
      showed that, in addition to the suppression of IL-2 production, NO-generating
      agents sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP)
      increased the secretion of IL-4 both in Th2 clones and EL4 T cells. The additive
      effect was dependent on the dose of SNP and SNAP. Augmentation of IL-4 production
      was detected with 1 microM SNP, and up to threefold increase in IL-4 secretion
      could be observed with higher concentrations of SNP/SNAP. NO also weakly
      increased the activation of IL-4 promoter. In contrast, NO markedly inhibited the
      induction of IL-2 promoter, which could account for most of the reduction in IL-2
      production. Analysis of the transcriptional elements on IL-2 and IL-4 promoters
      revealed a selective inactivation of NF-kappa B and NF-AT. It is suggested that
      despite the complex feedback network regulating NO production, the enhanced IL-4
      expression would lead to the expansion of Th2 cells once NO is generated.

PMID- 9155643
TI  - Flexibility in T-cell receptor ligand repertoires depends on MHC and T-cell
      receptor clonotype.
AB  - T-cell receptors (TCR) recognize peptides complexed to self-major
      histocompatibility complex (MHC) molecules. Recognition of peptide/MHC ligands by
      the TCR is highly peptide specific. However, certain TCRs can also recognize
      sequence-related and -unrelated ('mimicry') epitopes presented by homologous MHC
      molecules. Using two human, human leucocyte antigen-DR1 (HLA-DR1)-restricted T
      cell clones specific for HA p307-319, we identified several diverse combinations
      of peptide-MHC complexes that are functionally equivalent in their ability to
      trigger T-cell stimulation. These findings demonstrate that a single TCR can
      productively interact with different peptides complexed to self- as well as non
      self-MHC molecules. This extended reactivity is human leucocyte antigen (HLA)
      allele and TCR clonotype dependent, as the peptide repertoire recognized depends
      on the presenting HLA-DR molecule and varies among different TCRs that both
      recognize the HA p307-319/DR1 complex. Importantly, certain peptide analogues can
      completely change the HLA-restriction pattern of the TCR: T-cell recognition of
      the wild-type peptide that was absent in the context of a non-self HLA-DR
      molecule, was restored by complementing substitutions in altered peptide ligands,
      that could not be presented by the original restriction element. This mechanism
      may play an important role in allorecognition.

PMID- 9155645
TI  - Apoptosis in a Fas-resistant, T-cell receptor-sensitive human leukaemic T-cell
      clone.
AB  - The Fas (CD95) antigen plays a key role in regulating T-cell activation and
      survival. We have generated a Fas-resistant subclone of the human T-cell
      leukaemia line, H9, which is still able to undergo apoptosis in response to T
      cell receptor ligation. Molecular analyses revealed that resistance to Fas
      mediated apoptosis was due to a heterozygous mutation in the death domain of the
      Fas gene which generates a stop codon, and thus encodes a truncated Fas molecule.
      Fas ligation was able to induce apoptosis in the presence of cycloheximide,
      indicating that the mutant Fas molecule retained some signalling capability,
      which is death-domain independent. These cells will provide a useful tool for
      dissecting the complexities of Fas signalling pathways.

PMID- 9155644
TI  - The antigen receptor complex on cord B lymphocytes.
AB  - The neonatal immune system responds to a restricted range of antigens, producing
      largely IgM antibody of low affinity. Comparison of the components of the B-cell
      antigen receptor complex shows significantly elevated membrane levels of IgM in
      neonatal B cells, compared with adult cells. CD79, which acts as the signal
      transducer for membrane immunoglobulin, is elevated in parallel with IgM, while
      IgD is elevated to a lesser degree. CD19, CD21, CD22 and CD81, which are all
      involved in transmitting activation signals when immunoglobulin is engaged, are
      not elevated. CD32, which is involved in negative regulation of activation, is
      present at reduced levels on cord B cells. The elevation of B-cell membrane IgM
      persists during infancy. Neonatal B cells respond in vitro to interleukin-4 (IL
      4) by further elevation of membrane IgM levels. The elevated level of membrane
      IgM may make neonatal B cells easier to trigger by low concentrations of antigen,
      but in vitro activation and immunoglobulin modulation experiments did not show
      significant differences between cord and adult B-cell responses to anti-IgM.

PMID- 9155646
TI  - Retinol (vitamin A) is a cofactor in CD3-induced human T-lymphocyte activation.
AB  - Immunomodulatory effects of different retinoids have been demonstrated, both in
      vivo and in vitro, in different cellular lineages including human and murine
      thymocytes, human lung fibroblasts, Langerhans' cells, tumoral cells and natural
      killer (NK) cells; however, any attempt to demonstrate the effect of retinoids on
      human peripheral blood mononuclear cells (PBMC) resulted in negative results. In
      the present work, it is shown that retinol and retinoic acid induce a marked
      increase of proliferation on human PBMC from 32 unrelated healthy individuals,
      which had previously been stimulated with anti-CD3 antibodies 48 hr before. Serum
      free medium, specific retinoid concentration (10(-7) M) and a particular timing
      of retinol addition to the cultures (48 hr after CD3 stimulation) was necessary
      clearly to detect this retinol-enhancing effect. The increased proliferative
      response is specifically mediated via the clonotipic T-cell receptor-CD3 complex
      and correlates with the up-regulation of certain adhesion/activation markers on
      the T-lymphocyte surface: CD18, CD45RO and CD25; also Th1-type of cytokines
      (interleukin-2 and interferon-gamma) are found concordantly increased after
      retinoid costimulation, both measured by a direct protein measurement and by a
      specific mRNA increase. In addition, it is shown that the in vitro retinol
      costimulation is only present in immunodeficient patients who have no defect on
      CD3 molecules and activation pathway. The fact that retinol costimulate
      lymphocytes only via CD3 (and not via CD2 or CD28) and the lack of response
      enhancement in immunodeficients with impaired CD3 activation pathway indicates
      that retinoids may be used as therapeutic agents in immune system deficiencies
      that do not affect the clonotypic T-cell receptor.

PMID- 9155647
TI  - Cord blood CD4+ CD45RA+ T cells achieve a lower magnitude of activation when
      compared with their adult counterparts.
AB  - Highly purified CD4+ CD45RA+ cells from cord blood and peripheral blood from
      healthy adults were studied. The levels of expression of the CD2, CD3, CD4 and
      CD28 antigens were similar; however, CD45 and CD45RA antigen expression were
      slightly lower in cord cells. The reduced expression of the CD45RA antigen on
      cord CD4+ T cells was confirmed in whole blood. Functional assessment revealed
      deficiencies in cord CD4+ CD45RA+ T cells. Interleukin-2 (IL-2) production in
      response to specific triggering via CD2 monoclonal antibody (mAb) alone, or CD2
      mAb in combination with CD28 mAb showed marked underproduction (about 10% of
      adult production). When CD25 expression was examined, it was observed that the
      proportion of activated CD4+ CD45RA+ T cells in cord blood was lower than in
      adult (about 20% of adult expression). Proliferation to CD2 mAbs or CD2 + 28 mAbs
      of cord blood native cells was similarly depressed. Investigation of IL-2 mRNA
      expression under these stimulatory conditions paralleled the results observed for
      CD25 expression, IL-2 production and proliferation. When phorbol 12-myristate 13
      acetate (PMA) was added to the cells triggered with CD2 + 28mAbs, the responses
      examined were enhanced in both cord and adult blood with no significant
      differences between the groups. These findings suggest that under identical
      conditions of stimulation, purified cord blood CD4+ CD45RA+ T cells do not
      acquire similar activation status as their adult counterparts. These findings may
      help in understanding the reduced graft-versus-host disease (GVHD) observed in
      cord blood stem cell transplantation.

PMID- 9155648
TI  - Mouse hepatitis viral infection induces an extrathymic differentiation of the
      specific intrahepatic alpha beta-TCRintermediate LFA-1high T-cell population.
AB  - Mouse hepatitis virus type 3 (MHV3), a coronavirus, is an excellent model for the
      study of thymic and extrathymic T-cell subpopulation disorders induced during
      viral hepatitis. It was recently reported that, in addition to the intrathymic T
      cell differentiation pathway, an extrathymic differentiation pathway of alpha
      beta-T-cell receptor (TCR) T lymphocytes exists in the liver, and becomes
      important under pathological situations such as autoimmune diseases, malignancies
      or hepatic bacterial infections. In the present study, we compared the phenotypes
      of resident hepatic, splenic or thymic T-cell subpopulations during the acute
      viral hepatitis induced by HMV3 in susceptible C57BL/6 mice. The number of liver
      resident mononuclear cells (MNC) increased during the viral infection, while
      cellularity decreased. Single positive (SP) CD4+ cells strongly increased in both
      the liver and thymus, while double positive (DP) (CD4+ CD8+) cells, present in
      the liver and thymus of mock-infected mice, decreased in C57BL/6 mice during the
      viral infection. A shift of alpha beta-TCRintermediate T cells toward alpha beta
      TCRhigh was evidenced in the liver and thymus of infected mice, but not in the
      spleen. The few alpha beta-TCRint double negative (DN) (CD4-CD8-) cells also
      decreased following viral infection. alpha beta-TCRint or high lymphocytes
      expressing high levels of leucocyte function antigen-1 (LFA-1) increased in the
      liver of MHV3-infected mice. In addition, liver-resident T cells expressed
      strongly the CD44 (Pgp-1) activation marker, suggesting that they were either
      activated or antigen experienced during the viral infection. No significant
      change in T-cell subpopulations was detected in the spleen, suggesting that MHV3
      infection could induce an early in situ differentiation of resident hepatic T
      cells rather than a recruitment of lymphocytes from peripheral lymphoid organs.

PMID- 9155649
TI  - Comparison of intrahepatic lymphocytes from normal and growth hormone transgenic
      mice with chronic hepatitis and liver cancer.
AB  - Mice expressing an ovine growth hormone-mouse metallothionein promoter fusion
      gene (METoGH mice) develop chronic hepatitis which becomes progressively more
      severe over time, hepatocellular adenomas, and eventually carcinoma in the oldest
      animals. T-lymphocyte expression of activation/memory-associated markers was
      compared between liver and blood lymphocytes isolated from METoGH and non
      transgenic mice at 7, 10 and 12 months of age. The percentage of intrahepatic
      lymphocytes (IHL) which were CD4+ was markedly diminished in METoGH mice at all
      times. CD4+ and CD8+ IHL in METoGH mice expressed Ly-6A/6D at increased density,
      and were CD45RBlo at later time-points. Ly-6C+ and NK1.1+ CD4+ cells, which are
      common in normal mouse liver, were found at decreased frequency in METoGH livers.
      Further analysis demonstrated that, as a proportion of total T-cell receptor
      (TCR) alpha beta cells, NK1.1+ TCR alpha beta int CD4+ cell numbers (NKT cells)
      were diminished in the livers of METoGH mice. Observations made in METoGH mice
      support the hypothesis that sustained liver inflammation and hepatocellular
      injury may be linked to liver cancer. Additionally, it is possible that the
      relative lack of NKT cells may create an environment permissive for the growth of
      liver tumours.

PMID- 9155650
TI  - Suppression of murine thyroiditis via blockade of the CD40-CD40L interaction.
AB  - The CD40 ligand (gp39) is transiently expressed on activated CD4+ T cells and
      mediates cognate helper function by interacting with CD40 on B cells. Increasing
      evidence suggests, however, critical involvement of gp39 not only in antibody
      mediated responses but also in the development of effector T cells. Here, we have
      investigated the effect of in vivo gp39 blockade on the induction of murine
      experimental autoimmune thyroiditis (EAT), a T-cell-mediated disease. Over a 5
      week period, EAT was induced in SJL mice with thyroglobulin (Tg) and adjuvant.
      Concomitantly, mice received intraperitoneal (i.p.) injections of MR1, a gp39
      specific hamster monoclonal antibody (mAb), at 4-day intervals. Control mice were
      challenged with Tg but received equivalent doses of hamster immunoglobulin (HIg).
      It was observed that the control mice developed severe thyroiditis whereas the
      MR1-treated mice exhibited very low levels of infiltration that were mostly focal
      in nature. Blockade of gp39 was effective since the Tg-specific IgG titres were
      low or undetectable in all MR1-treated animals compared with the controls. In
      addition, upon restimulation with Tg in vitro, lymph node cells (LNC) from Tg
      primed, MR1-treated mice proliferated less strongly and secreted significantly
      lower amounts of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) than LNC
      from untreated or HIg-treated controls. These results strongly suggest that in
      vivo blockade of gp39 suppresses EAT by inhibiting the priming of inflammatory Tg
      specific T-helper type 1 cells.

PMID- 9155651
TI  - Demonstration of cytoplasmic CD32 (Fc gamma RII) within human lymphocytes
      following microwave treatment.
AB  - We have recently described a cytoplasmic from of CD32 (Fc gamma RII) within the
      vast majority of normal human peripheral blood lymphocytes (PBL) including T
      cells. The function of cytoplasmic CD32 is not known. These flow cytometric
      studies were conducted using single cell suspensions of PBL that had been pre
      fixed and permeabilized using methanol/triton-X-100. In this study we have
      attempted to visualize cytoplasmic CD32 by immunocytochemistry using normal PBL
      processed in various ways and have also looked for CD32 within tissue
      lymphocytes. Weak cytoplasmic CD32 staining was observed in paraffin sections of
      normal lymphocytes but only when sections were microwave treated. The intensity
      of staining for CD32 did however, appear to be much stronger within infiltrating
      lymphocytes found in autoimmune diseases or in rejecting allografts: an
      observation that suggests that up-regulation of cytoplasmic CD32 may occur when T
      cells become activated in vivo. Microwave treatment of PBL suspensions was shown
      to disrupt the outer cell membrane, thus effectively permeabilizing the cell and
      allowing for the detection of cytoplasmic components, like CD32, by flow
      cytometry. Microwave treatment may, therefore, afford an alternative method for
      cell permeabilization and may prove to be a useful method for the study of
      cytoplasmic molecules in cell suspensions and in paraffin-embedded tissues.

PMID- 9155652
TI  - Pentoxifylline in vivo and in vitro down-regulates the expression of the
      intercellular adhesion molecule-1 in monocytes.
AB  - Since pentoxifylline (PTX) was recently recognized as a substance with
      antiinflammatory capacities, we studied the in vivo and in vitro effect of PTX on
      the expression of the intercellular adhesion molecule-1 (ICAM-1) on human
      monocytes. For this purpose four healthy volunteers were treated with PTX (5 x
      400 mg/day) for 2 days. Monocytes were isolated before and after PTX treatment
      and ICAM-1 expression was investigated. As shown by fluorescence-activated cell
      sorter (FACS) analysis, cultured monocytes isolated after oral application of PTX
      expressed significantly decreased amounts of ICAM-1 when compared with monocytes
      collected prior to oral PTX application. Northern blot analysis revealed reduced
      amounts of ICAM-1 mRNA in monocytes derived from volunteers after oral PTX
      treatment in comparison with monocytes isolated before oral PTX administration.
      Similarly, in monocytes treated with PTX (200 micrograms/ml) in vitro ICAM-1 was
      found decreased both at the protein and mRNA level in comparison with untreated
      cells. The inhibitory effect of PTX on ICAM-1 expression in monocytes could be
      reversed by the addition of exogenous tumour necrosis factor-alpha (TNF-alpha;
      200 U/ml) suggesting that ICAM-1 down-regulation is mediated secondary to TNF
      alpha suppression by PTX. The specific role of TNF-alpha in mediating ICAM-1
      expression in cultured monocytes could be confirmed by the finding that a
      neutralizing anti-TNF-alpha antibody partially down-regulated ICAM-1 expression.
      The observed suppressive in vivo and in vitro effects of PTX on ICAM-1 expression
      in monocytes may contribute to the recently described antiinflammatory effects of
      PTX, e.g. in sepsis or allergic contact dermatitis.

PMID- 9155653
TI  - Modulatory effect of interleukin-10 on the production of platelet-activating
      factor and superoxide anions by human leucocytes.
AB  - We observed that human monocytes (MO) and polymorphonuclear neutrophils (PMN)
      stimulated by lipopolysaccharide (LPS) produce platelet-activating factor (PAF)
      in a pattern characterized by an early and a delayed peak of synthesis. The early
      peak of PAF synthesis was due to a direct stimulation of these cells through
      mCD14 receptor as it was inhibited by anti-CD14 monoclonal antibody. The delayed
      and sustained peak of PAF synthesis was dependent on protein synthesis and
      cytokine production as shown by the inhibitory effect of cycloheximide on both MO
      and PMN, and of anti-tumour necrosis factor-alpha (anti-TNF-alpha) and of anti
      interleukin-8 (anti-IL-8) neutralizing antibodies on MO and PMN respectively. IL
      10 completely prevented this second, cytokine-dependent peak of PAF synthesis. In
      contrast, IL-10 markedly enhanced the first peak of PAF synthesis both in MO and
      PMN. Moreover, IL-10 was shown to modulate the production of superoxide anions
      (O2-) on both MO and PMN. As suggested by previous studies, IL-10 inhibited the
      delayed production of O2-. In the present study, we observed that IL-10 directly
      stimulated an early production of O2-. In addition, IL-10 enhanced the synthesis
      of O2- by MO and PMN challenged with LPS. The IL-10-induced O2- production was
      dependent, at least in part, from its effect on PAF synthesis, as it was
      inhibited by the PAF receptor antagonist WEB 2170. These results suggest that IL
      10 may upregulate the early synthesis of PAF and O2- triggered by direct LPS
      stimulation, whereas it may downregulate the delayed production of these
      mediators.

PMID- 9155654
TI  - The beta 1 integrin, very late activation antigen-4 on human neutrophils can
      contribute to neutrophil migration through connective tissue fibroblast barriers.
AB  - Polymorphonuclear leucocyte (PMNL) accumulation in extravascular tissues and
      inflammatory exudates is dependent on their migration through blood vessel
      endothelium and then through connective tissue. Previously we utilized a barrier
      of human synovial and dermal fibroblasts (HSF or HDF) grown on microporous
      filters, as a model of PMNL migration through connective tissue. Those studies
      showed that beta 2 (CD18) and the beta 1 integrins, very late activation antigen
      5 (VLA-5) and VLA-6, in part mediate this PMNL migration. Here we report that VLA
      4, which can also be expressed at low levels on activated PMNL, is also involved
      in PMNL migration induced by C5a through fibroblast (HSF and HDF) barriers,
      because monoclonal antibody (mAb) to VLA-4 significantly inhibited (by 20-30%)
      PMNL migration. Blocking the function of CD18, VLA-5 or VLA-6 was not required
      for detection of the VLA-4-mediated migration. Combination treatment with mAb to
      VLA-4 and with mAb to VLA-5 or to VLA-6 further inhibited PMNL migration,
      irrespective of whether CD11/CD18 mechanisms were blocked with anti-CD18 mAb or
      not. Treatment of PMNL with a peptide based on the VLA-4-binding domain in the CS
      1 fragment of fibronectin, but not a control peptide, inhibited PMNL migration to
      a comparable extent to treatment with mAb to VLA-4. A low level of VLA-4 was
      expressed on C5a-activated PMNL, detected by immunofluorescence flow cytometry.
      These results suggest that VLA-4 can be mobilized by human peripheral blood PMNL
      and can, in addition to VLA-5, VLA-6 and CD11/CD18 integrins, mediate PMNL
      migration through connective tissue. This is in marked contrast to PMNL
      transendothelial migration, where beta 1 integrins appear to play no significant
      role.

PMID- 9155656
TI  - Transgenic technology: an introduction.

PMID- 9155657
TI  - Transgenic technology: principles.

PMID- 9155655
TI  - Cellular redox status influences both cytotoxic and NF-kappa B activation in
      natural killer cells.
AB  - The role of cellular redox status in both cytotoxic activity and NF-kappa B
      activation in natural killer (NK) cells was investigated. The results indicate
      that stimulation of NK cells, either freshly isolated from peripheral blood
      lymphocytes (PBL) or long-term cultured NK clones, with specific cell targets
      results in an increased binding activity of NF-kappa B and AP-1 transcription
      factors measured by gel retardation. Pretreatment of NK cells with the
      antioxidant pyrrolidine dithiocarbarmate (PDTC) leads to the inhibition of NF
      kappa B activation but the AP-1 binding to DNA was superinduced. The inhibition
      of NF-kappa B by PDTC paralleled with an inhibition of spontaneous cytotoxicity
      mediated by NK cells. Moreover, the inhibitors of serine proteases, N-alpha-tosyl
      L-lysine chloromethyl ketone and N-alpha-tosyl-L-phenylalanine chloromethyl
      ketone, also blocked the cytolytic activity of NK cells against the sensitive
      target K562. In contrast, NK activity was not affected by pretreatment of the
      effector cells with the proteasome inhibitor N-acetyl-leu-leu-norleucinal which
      selectively inhibits NF-kappa B activation. Altogether, these results support the
      hypothesis that the activation of NK cells involved transcriptional and post
      transcriptional events, and that reactive intermediates may play an important
      role in the molecular processes related with the generation of a cytotoxic
      response by NK cells.

PMID- 9155658
TI  - Transgenic rodents in toxicology.

PMID- 9155659
TI  - Transgenic model applications to drug discovery.

PMID- 9155660
TI  - Embryonic stem-cell-like cell lines of the species rat and Bovinae.

PMID- 9155661
TI  - Conditional mutagenesis in mice: the Cre/loxP recombination system.

PMID- 9155662
TI  - Transgenic mice to study viral pathogenesis and autoimmunity.

PMID- 9155663
TI  - The use of transgenic mice in the investigation of transmissible spongiform
      encephalopathies.

PMID- 9155664
TI  - Diagnosis of thin melanoma.

PMID- 9155665
TI  - Pathological approach to the diagnosis of hydrocephalus.

PMID- 9155667
TI  - ACP Broadsheet No 150. March 1997. Antenatal serological testing and prevention
      of haemolytic disease of the newborn.

PMID- 9155666
TI  - Cerebrospinal fluid analysis in clinical diagnosis.

PMID- 9155668
TI  - Alcohol estimation at necropsy: epidemiology, economics, and the elderly.
AB  - AIMS: To gather data on blood alcohol concentrations in a forensic necropsy
      population and to analyse the information on trends that may predict where
      alcohol testing is going to prove cost-effective. METHODS: Alcohol assays were
      performed on blood, urine, and vitreous samples in 1620 consecutive medicolegal
      necropsy examinations. RESULTS: Alcohol was detected in only 7% of natural deaths
      from all causes and in four of 40 deaths categorised as unknown/obscure. Alcohol
      concentrations > or = 350 mg/100 ml were found in nine drug/alcohol abuse deaths
      (range 362-506 mg/100 ml), five accidental deaths (356-504 mg/100 ml), and one
      homicide victim (400 mg/100 ml). Those categorised as alcohol abusers were
      represented in all but one category of death (unknown/obscure deaths in males),
      showing that many true alcoholics die with their alcoholism rather than of it;
      39% of males and 34% of females with histories of alcohol abuse had alcohol
      present in their blood at necropsy at concentrations > or = 50 mg/100 ml, v only
      9% (male) and 6% (female) without such history. CONCLUSIONS: The study highlights
      the problems of elderly and "hidden" alcoholics and illustrates cases where
      routine assays would provide additional significant information. Routine alcohol
      testing is useful in all cases of suspected unnatural death but universal testing
      of forensic necropsies is not cost-effective.

PMID- 9155669
TI  - A nationwide survey of observer variation in the diagnosis of thin cutaneous
      malignant melanoma including the MIN terminology. CRC Melanoma Pathology Panel.
AB  - AIM: To investigate observer variation in the diagnosis of thin cutaneous
      malignant melanoma and related lesions in a nationwide sample of
      histopathologists in the UK. METHODS: Out of a random sample of 195 pathologists,
      148 (76%) participated in two circulations, the first with 20 slides and the
      second with 25 slides. The results were compared with those for the Cancer
      Research Campaign (CRC) Melanoma Pathology Panel, consisting of seven
      histopathologists and one dermatopathologist, which had developed and evaluated
      diagnostic criteria. RESULTS: In the first circulation, when no standardised
      diagnostic criteria were used, a fair level of agreement was achieved for an
      overall diagnosis using the categories benign naevi with no atypia, benign naevi
      with atypia and melanoma (Kappa = 0.45). This was low compared with the agreement
      of the panel who used agreed criteria (Kappa = 0.75). Moreover, participants in
      the nationwide survey were more likely to diagnose melanoma and less likely to
      diagnose benign naevi without atypia than the panel. In the second circulation,
      when diagnostic criteria and diagrams were used, there was a higher level of
      agreement for overall diagnosis using the categories benign, melanocytic
      intraepidermal neoplasia (MIN) with or without microinvasion and melanoma with
      vertical growth phase, and was the same as that achieved by the panel using the
      same criteria (Kappa = 0.68). CONCLUSIONS: As the incidence rate of thin
      melanomas has been increasing in the UK, it is important that standardised
      diagnostic criteria are used to ensure accurate reporting of incidence and
      correct management of patients. The use of MIN and the vertical growth phase
      seemed to be generally acceptable.

PMID- 9155670
TI  - Non-specifically labelled cells that simulate bone marrow metastases in patients
      with non-metastatic breast cancer.
AB  - AIMS: To determine whether the presence of disseminated bone marrow tumour cells
      at diagnosis is a prognostic factor for breast cancer patients at high risk of
      recurrence or bone metastasis, and to assess their presence as a criterion for
      evaluation of the potential benefits of adjuvant chemotherapy. METHODS: Multiple
      bone marrow aspirates from 72 breast cancer patients free from metastasis were
      obtained during surgery at the time of diagnosis and were tested immunologically
      by alkaline phosphatase antialkaline phosphatase technique with a panel of three
      antiepithelial monoclonal antibodies (MoAb) KL1, EMA, and HMFG2. RESULTS: In nine
      of 72 patients, with each MoAb tested, numerous strongly positive cells always
      isolated were observed. However, it was demonstrated that these cells were non
      specifically labelled and could be found in normal controls. CONCLUSIONS: There
      was no evidence of marrow tumour cells in 72 operable breast cancer patients. It
      is suggested that published results may be greatly overestimated and that non
      specific labelling may be undetected. More specific MoAb should be found and a
      correlation with molecular biology should be performed if this criterion is to be
      considered as a prognostic factor.

PMID- 9155671
TI  - Mutation analysis of the p53, APC, and p16 genes in the Barrett's oesophagus,
      dysplasia, and adenocarcinoma.
AB  - AIMS: To study the loss of heterozygosity and the presence of mutations at the
      p53, p16/CDKN2, and APC genes in Barrett's oesophagus, low grade dysplastic
      oesophageal epithelium, and adenocarcinoma of the oesophagus; to relate the
      presence of alterations at these genes with the progression from Barrett's
      oesophagus to adenocarcinoma. METHODS: DNA was extracted from paraffin blocks
      containing tissue from Barrett's oesophagus (12 samples), low grade dysplasia (15
      cases), and adenocarcinoma (14 cases). Loss of heterozygosity (LOH) at the p53,
      p16, and APC genes was determined by comparing the autoradiographic patterns of
      several microsatellite markers between the normal tissue and the malignant tissue
      counterpart. SSCP was used to determine the presence of mutations at p53 (exons 5
      to 8), p16 (exon 2), and APC. Homozygous deletion of the p16 gene was defined
      through polymerase chain reaction followed by Southern blot. RESULTS: LOH at the
      p53, p16, and APC genes was not observed in Barrett's oesophagus without
      dysplasia, and increased to 90% (p53), 89% (p16), and 60% (APC) in the
      adenocarcinomas. The p53 gene was mutated in only two adenocarcinomas (codons 175
      and 245). In one case a mutation at the APC gene (codon 1297) was found. No
      patient had mutation at the second exon of p16. However, this gene was
      homozygously deleted in three of the 12 adenocarcinomas. CONCLUSIONS: The tumour
      suppressor genes p53, p16, and APC are often deleted in adenocarcinomas derived
      from Barrett's oesophagus. Mutations at these genes are also found in the
      adenocarcinomas, including the homozygous deletion of the p16 gene. However, the
      absence of genetic alterations in the Barrett's oesophagus and the low grade
      dysplastic epithelia suggest that mutations at these genes develop later in the
      progression from Barrett's oesophagus to adenocarcinoma.

PMID- 9155672
TI  - Tumour recurrence is associated with Jass grouping but not with differences in E
      cadherin expression in moderately differentiated Dukes' B colorectal cancers.
AB  - AIMS: To assess whether immunohistochemical expression of the putative invasion
      suppressor, E-cadherin, is associated with tumour recurrence in colorectal
      cancer, independent of Dukes' stage and degree of differentiation, and thus to
      determine whether measurement of E-cadherin is clinically useful. METHODS: 90
      moderately differentiated Dukes' B colorectal carcinomas from patients who had
      been followed up for at least six years were examined. All were from curative
      resections performed at St Mark's Hospital and the tumours were shown, on
      histology, to be clear of all resection margins. Tumours were reviewed and
      additionally classified in accordance with the Jass grouping system.
      Immunohistochemical analysis of E-cadherin expression was performed for each
      tumour using the monoclonal antibody HECD 1. RESULTS: The Jass group ranged
      between I and III and there was a significant association between Jass group and
      tumour recurrence (p < 0.05). Positive E-cadherin expression was seen in 40/69
      (58%) of non-recurrent and 13/21 (62%) recurrent cases respectively. There was no
      significant difference in E-cadherin expression between the two groups of
      tumours. CONCLUSIONS: Even when controlled for Dukes' stage and differentiation,
      the Jass grouping system yields useful prognostic information; E-cadherin,
      however, does not predict outcome in the important group of moderately
      differentiated Dukes' B colon cancers, and may be of little independent
      prognostic value in other colon cancers.

PMID- 9155674
TI  - Detection of CMV DNA in bone marrow transplant recipients: plasma versus
      leucocyte polymerase chain reaction.
AB  - AIMS: To compare the nested polymerase chain reaction (PCR) assay for the
      detection of cytomegalovirus (CMV) DNA in peripheral blood leucocytes and plasma
      obtained from heparinised blood; to determine the efficiency of various DNA
      extraction methods to minimise inhibition of plasma PCR and their effect on the
      sensitivity of plasma PCR; to determine the inhibitory effect of heparin,
      dextran, and EDTA on the CMV PCR assay. METHODS: 217 heparinised blood specimens
      from 58 bone marrow transplant patients were processed and the sensitivities and
      specificities of the PCR assays using peripheral blood leucocytes and plasma
      (with simple, Instagene, and Geneclean extraction methods) were compared to those
      of conventional CMV culture. In a separate experiment, dilutions of heparin,
      dextran, and EDTA were included in PCR assays. RESULTS: The detection of CMV DNA
      using peripheral blood leucocytes for PCR assay was significantly more sensitive
      (100%) than when using plasma (60%). Instagene and Geneclean extraction removed
      inherent inhibition but did not improve the sensitivity of the plasma PCR
      reaction. Heparin had an inhibitory effect on PCR. CONCLUSIONS: PCR assay using
      peripheral blood leucocytes is better than plasma for guiding the prescription of
      ganciclovir to bone marrow transplant patients. Heparin is inhibitory to the
      plasma PCR reaction.

PMID- 9155673
TI  - Retrovirus in salivary glands from patients with Sjogren's syndrome.
AB  - AIMS: To investigate the possibility of an immune response to retroviral antigens
      or of detecting retrovirus in Sjogren's syndrome. METHODS: Retroviruses were
      sought in labial salivary glands and peripheral blood mononuclear cells from
      patients with Sjogren's syndrome by immunoblotting assay, immunohistochemical
      assay, polymerase chain reaction (PCR), reverse transcriptase (RT) activity
      assay, and transmission electron microscopy. RESULTS: Sera from five of 15
      patients with Sjogren's syndrome (33%) reacted against p24 group specific antigen
      (gag) of human immunodeficiency virus (HIV). Labial salivary gland biopsy
      specimens from seven of the 15 patients with Sjogren's syndrome (47%) contained
      an epithelial cytoplasmic protein reactive with a monoclonal antibody to p24 of
      HIV. PCR was performed to detect HIV and human T lymphotropic virus type I (HTLV
      I) genes from salivary gland tissues and peripheral blood mononuclear cells from
      patients with Sjogren's syndrome. Mn2+ dependent, Mg2+ independent RT activity
      was detected in the salivary gland tissues in three of 10 patients. A-type-like
      retroviral particles were observed in epithelial cells of salivary glands by
      transmission electron microscopy. Target genes for HIV and HTLV-I were not found
      in any of the salivary gland tissues or peripheral blood mononuclear cells from
      Sjogren's syndrome patients. CONCLUSIONS: The data suggest the presence of an
      unknown retrovirus similar to HIV in the salivary gland which might be involved
      in the pathogenesis of a subpopulation in Sjogren's syndrome.

PMID- 9155676
TI  - Use of prototype automated blood culture system and gas-liquid chromatography for
      the analysis of continuous ambulatory peritoneal dialysis associated infection.
AB  - AIMS: (1) To compare the recovery of organisms from continuous ambulatory
      peritoneal dialysis (CAPD) effluent fluid obtained from patients with clinical
      evidence of peritonitis, with an automated system (AS) and the Septichek blood
      culture system; (2) to evaluate the times to detection of organisms with the two
      systems; (3) to identify anaerobes from CAPD samples by extended anaerobic
      culture and gas-liquid chromatography (GLC). METHODS: 168 CAPD effluent fluid
      samples were studied, representing 157 episodes of peritonitis in 97 patients.
      CAPD samples were inoculated into two AS bottles-one anaerobic, one aerobic-and a
      Septichek bottle; samples were also examined for cell count, Gram stain, and
      direct culture. Culture bottles were then subcultured onto various media, and any
      organisms isolated were identified. After routine culture, GLC was performed on
      culture fluid in the anaerobic AS and Septichek bottles. When volatile fatty
      acids were detected, the broths were cultured anaerobically on specialised medium
      for a further five days. RESULTS: 147 organisms were isolated from the 168
      samples: 96 (57%) yielded growth of significant organisms by direct culture, as
      compared to 129 (76.8%) by both AS and Septichek. There was no significant
      difference in isolation rates between AS and Septichek, but time to detection was
      more rapid with the AS system (p < 0.002). GLC showed volatile fatty acid in 15
      specimens; of these, 14 subsequently grew anaerobic organisms. CONCLUSIONS: AS
      was comparable to Septichek for numbers of isolations. Speed to detection was
      faster with the AS, which may be an advantage in management of patients with CAPD
      peritonitis. GLC showed anaerobes in several cases which would not have been
      detected without prolonged anaerobic culture; thus anaerobic cultures are
      recommended for patients who are unresponsive to antimicrobials or who have
      evidence of bowel perforation.

PMID- 9155675
TI  - Plasma proteins in children with trichuris dysentery syndrome.
AB  - AIMS: To determine whether in Trichuris trichiura dysentery there is (1) evidence
      of a systemic inflammatory response, (2) evidence that the plasma protein
      disturbance has special characteristics compared with uninfected children in the
      endemic environment. METHODS: Three groups of children (age 1.6 to 11.4 years)
      were studied: 53 cases of trichuris dysentery syndrome (TDS), 16 cases of chronic
      non-secretory diarrhoea not infected with the parasite ("disease controls", DC),
      and 20 asymptomatic, parasite-free primary schoolchildren (normal controls, NC).
      C reactive protein, alpha 1 antitrypsin, caeruloplasmin, albumin, total globulin,
      fibrinogen, fibronectin, ferritin, and transferrin were measured on a single
      occasion for each. The study was thus a cross sectional descriptive survey for
      group comparison. Plasma viscosity was measured on admission for TDS and DC and
      repeated after six weeks and six months for TDS. RESULTS: Plasma C reactive
      protein, alpha 1 antitrypsin, total globulin, fibronectin, and viscosity were
      significantly higher in TDS than in NC. DC children also had acute phase protein
      elevations (C reactive protein, caeruloplasmin, viscosity). However, the increase
      in caeruloplasmin was specific to the DC group while an increase in fibronectin
      was specific to the TDS group. Serial measurement of viscosity in TDS showed a
      modest but significant fall during the six months following treatment.
      CONCLUSIONS: There is an acute phase response in intense trichuriasis and a
      specific elevation of plasma fibronectin. Plasma viscosity remains abnormally
      high six months after treatment, although lower than at diagnosis.

PMID- 9155677
TI  - Possible lethal enhancement of toxins from putative periodontopathogens by
      nicotine: implications for periodontal disease.
AB  - AIM: To test the hypothesis that lethal synergy in the chick embryo model may
      occur between nicotine and bacterial products (cell-free extracellular toxins and
      cell lysates) of five putative periodontopathogens. METHODS: The lethality of
      cell-free extracellular toxins and cell lysates of five periodontal species was
      assessed with or without nicotine in the chick embryo assay system. Ten putative
      periodontopathogens (five species) were studied: Prevotella intermedia (n = 5),
      Porphyromonas gingivalis (n = 1), Porphyromonas asaccharolytica (n = 1),
      Fusobacterium nucleatum (n = 2), and Fusobacterium necrophorum (n = 1). RESULTS:
      Simultaneous testing of cell-free extracellular toxins from isolates W50, PS2,
      PS3, PS4, and PS5 and nicotine resulted in a percentage kill significantly
      greater than expected (Fisher's Exact test). Simultaneous testing of cell lysates
      from isolates W50, PS2, and PS5 and nicotine resulted in a percentage kill
      significantly greater than expected (Fisher's Exact test). CONCLUSIONS: Lethal
      synergy in the chick embryo model may occur between nicotine and toxins from
      putative periodontopathogens (both cell-free extracellular toxins and cell
      lysates). This may be an important mechanism by which smoking increases the
      severity of periodontal disease.

PMID- 9155678
TI  - Urethral malignant melanoma closely mimicking urothelial carcinoma.
AB  - Primary malignant melanoma of the urethra is very rare. In the male, the distal
      urethra is the most common site. The histopathology does not usually differ from
      that of melanoma at other body sites. This report describes a case of urethral
      malignant melanoma which closely resembled urethral carcinoma. It showed both
      papillary and solid growth, and the diagnosis only became apparent from special
      stains. Pathologists should be aware of this rare occurrence.

PMID- 9155679
TI  - Mucopolysaccharidosis type VII associated with hydrops fetalis: histopathological
      and ultrastructural features with genetic implications.
AB  - A case of mucopolysaccharidosis type VII (MPS VII, beta glucuronidase deficiency)
      causing fatal hydrops fetalis in the third trimester is presented. The diagnosis
      was suspected on histopathological examination by the presence of foam cells in
      many of the viscera and foamy change in the placental Hofbauer cells. Electron
      microscopy showed empty cytoplasmic inclusion bodies within macrophages and in
      the Hofbauer cells. Enzyme assay of cultured fibroblasts showed markedly
      deficient beta glucuronidase activity, thus confirming the diagnosis. A detailed
      and thorough histopathological examination of hydrops fetalis cases is important
      to detect subtle features of inherited metabolic disorders. Use of a structured
      necropsy protocol is recommended for cases of non-immune hydrops. Electron
      microscopy is a useful adjunct to light microscopy in cases where an inherited
      metabolic disorder is suspected. Precise necropsy diagnosis is important as there
      are implications for genetic counselling and possible prenatal diagnosis in
      subsequent pregnancies.

PMID- 9155680
TI  - Hashimoto's thyroiditis associated with urticaria and angio-oedema: disappearance
      of cutaneous and mucosal manifestations after thyroidectomy.
AB  - A 60 year old woman affected by Hashimoto's thyroiditis presented with a history
      of recurring episodes of urticaria and angio-oedema. Clinical and laboratory
      evaluation of the patient excluded allergy to external agents, hereditary angio
      oedema, and occult infections. A pathogenic relation between Hashimoto's
      thyroiditis and chronic urticaria/angio-oedema was suspected. However, treatment
      with L-thyroxine had no influence on the frequency and severity of the cutaneous
      and mucosal manifestations, which occurred almost daily and required repeated
      administration of steroids. The patient therefore underwent total thyroidectomy.
      Cytometric analysis of intrathyroidal lymphocyte subsets showed unusual
      abnormalities. Urticaria and angio-oedema completely remitted after surgery; 18
      months postoperatively the patient was still asymptomatic.

PMID- 9155681
TI  - Comparison of methods for the isolation of methicillin resistant Staphylococcus
      aureus.
AB  - The control of methicillin resistant Staphylococcus aureus (MRSA) relies on the
      rapid and sensitive detection of carriage. The roles of an enrichment broth,
      duration of incubation, and Baird-Parker medium containing ciprofloxacin (BPC)
      were evaluated in comparison with standard media in a centre where the prevalence
      of ciprofloxacin resistance among MRSA is over 98%. Screening swabs from 402
      sites were plated onto BPC, mannitol salt agar (MSA), and MSA with methicillin
      (MMSA). The swabs were enriched in Tryptone-T broth with 6% salt for 24 hours and
      the broths subcultured onto BPC, MSA, and MMSA. MRSA was isolated from 134 swabs.
      Significantly more isolates were obtained by incubating culture plates for 42
      hours rather than 18 hours, by the use of broth enrichment, and by addition of
      methicillin or ciprofloxacin to media. BPC was the most sensitive medium (107
      isolates (80%) by direct culture at 42 hours), grew the fewest contaminants, and
      allowed provisional reporting of 73% of isolates at 18 hours by colonial
      appearance and use of Staphaurex Plus rapid latex reagent. This may allow the
      introduction of infection control measures a day earlier than when other
      established methods are used.

PMID- 9155683
TI  - Bone marrow necrosis in antiphospholipid syndrome.
AB  - Bone marrow necrosis (BMN) is a relatively rare entity and has been associated
      with a poor prognosis. It is most commonly found in patients with neoplastic
      disorders, severe infections and sickle cell anemia. An unusual case of
      antiphospholipid syndrome (APS) with extensive bone marrow necrosis is described
      in a 27 year old woman. The patient presented with severe pancytopenia, some
      cognitive impairment resulting from a previous cerebrovascular accident, fever,
      hypertension, dyspnoea, tachycardia, hepatosplenomegaly, and vaginal bleeding.
      Her laboratory findings included a strongly positive Coombs' test (anti-IgG and
      anti-C3d), a prothrombin time of 23 seconds and an activated partial
      thromboplastin time of 45 seconds. Anticardiolipin antibody tests were positive.
      Antinuclear and anti-DNA antibodies were negative but the anti-SM test was
      positive. A bone marrow biopsy specimen was reported as showing extensive
      necrosis. The patient was treated with steroids, transfusion, and plasma exchange
      with some clinical improvement but her pancytopenia did not respond and
      necessitated frequent transfusions. This case lends further support to the
      association between APS and BMN.

PMID- 9155682
TI  - A fatal postpartum Clostridium sordellii associated toxic shock syndrome.
AB  - Clostridium sordellii is an infrequent human pathogen. It has been demonstrated
      to be occasionally responsible for myonecrosis or gas gangrene. Interestingly, in
      the obstetric literature, some cases of postpartum maternal deaths have been
      associated with C sordellii infection causing a rapidly lethal toxin mediated
      syndrome. This is the first reported case of postpartum death in a 29 year old
      woman, in which a toxigenic C sordellii was isolated from the patient's blood
      antemortem during the fatal toxic shock, strongly indicating its role in this
      rare syndrome.

PMID- 9155684
TI  - A simple technique for identifying the adrenal glands at necropsy.
AB  - There is no detailed and practical description of how to identify the adrenal
      glands at necropsy. A simple technique is described, based on anatomical
      location. After removing the aorta by the Rokitansky method, the inferior vena
      cava is opened. The orifice of the right adrenal vein is identified just above
      the right renal vein, and a probe is inserted into it as a marker. The right
      adrenal gland is identified at the centre above the line of the probe after
      separation of the diaphragm, which is attached to the liver. The left adrenal
      vein arises as the first bifurcation of the left renal vein after its origin from
      the inferior vena cava. A probe is inserted into it and the vein is opened along
      the probe. The left adrenal gland is identified at the left side of the left
      adrenal vein, embedded in fat. This method is also useful in cases with severe
      adhesion, fibrosis, or metastases.

PMID- 9155685
TI  - Multiple drug resistant tuberculosis.

PMID- 9155686
TI  - Rights of possession in human corpses.

PMID- 9155687
TI  - Unrelated donor bone marrow transplantation: its use in leukaemias and allied
      disorders. Consensus statement from the RCPE/Consensus Conference on Unrelated
      Donor BMT held on 29 and 30 October 1996.

PMID- 9155689
TI  - Telomerase in the early detection of cancer.
AB  - Although there is justifiable optimism regarding telomerase activity and early
      detection of cancer, it is important to point out that there is much that remains
      to be understood and additional validation studies will be required before
      knowledge of telomerase activity will be useful in decisions regarding patient
      management. A key question is whether we will be able to distinguish those
      cancers that are going to progress from those cancers that are not by detecting
      telomerase activity. Molecular staging using markers such as telomerase activity
      in combination with other molecular markers may be particularly useful in this
      regard. Basic scientists and clinicians must work together if this strategy is to
      mature. Telomerase inhibitors in the treatment of cancer are awaited with great
      anticipation.

PMID- 9155688
TI  - Guidelines for the initial biopsy diagnosis of suspected chronic idiopathic
      inflammatory bowel disease. The British Society of Gastroenterology Initiative.

PMID- 9155690
TI  - Telomerase activity and in situ telomerase RNA expression in malignant and non
      malignant lymph nodes.
AB  - AIMS/BACKGROUND: Telomerase, an enzyme associated with cellular immortality, is
      expressed by most malignant tumours, but is inactive in normal somatic cells
      except for male germ cells and proliferating stem cells. Thus, the measurement of
      telomerase activity in tissue samples may provide useful diagnostic and
      prognostic information. The aim of this study was to determine whether telomerase
      expression is useful for the detection of occult malignant cells in lymph nodes.
      METHODS: Telomerase activity was compared with histological findings in 123
      surgically removed lymph nodes submitted for routine or frozen section diagnosis.
      Telomerase activity was measured using a modified, semi-quantitative PCR-based
      telomeric repeat amplification protocol (TRAP). The assay was adapted for single
      5 microns OCT embedded cryostat sections. In either fresh tissues or cryostat
      sections, normalised activity was linear when compared with protein
      concentration. Furthermore, using an in situ hybridisation method, the human
      telomerase RNA (hTR) component was measured in a subset of negative and positive
      nodes. RESULTS: Most (96%) of the 97 histologically negative nodes expressed low
      levels of activity (mean value of positive samples = 3.0 units/microgram protein)
      which may be derived from activated lymphocytes that express telomerase activity.
      All 26 malignant nodes (17 metastases, nine lymphomas) expressed telomerase (mean
      value = 17.8 units/microgram protein). The rank order levels between the two
      groups differed significantly (p = 0.0002). In situ results showed clearly that
      the hTR was expressed relatively highly in metastatic cancer cells and at lower
      levels in germinal centres of secondary follicles. CONCLUSIONS: Although
      expression of telomerase by activated lymphocytes may limit its usefulness,
      measurement of enzyme activity combined with detection of hTR using in situ
      hybridisation may assist in the histopathological diagnosis of lymph nodes.

PMID- 9155691
TI  - Semiautomatic quantitation of macrophages in human renal biopsy specimens in
      proteinuric states.
AB  - AIMS: To develop and validate a rapid and economical semiautomated approach to
      the measurement of immunostainable tissue components which is applicable to
      routine diagnostic practice. To apply this approach to the measurement of
      macrophages in renal biopsy specimens in nephrotic states, as protein in the
      renal tubules may induce macrophage infiltration, and the morphology of
      macrophages in tissue sections does not lend itself to cell counting. METHODS:
      Macrophages were identified by immunostaining with a pan-macrophage marker,
      followed by digital image capture and analysis using a macro procedure written
      for the freeware image analysis program NIH-Image. RESULTS: The method was rapid,
      robust and accurate to within the limits imposed by sampling error inherent in
      the use of small needle biopsy specimens. Very few macrophages are found in
      normal kidney (mean volume fraction (+/- 95% confidence limits) 0.04% (0.02%))
      but infiltration of macrophages was detected in minimal change nephropathy (0.29%
      (0.12%)) and in membranous glomerulonephritis (0.42% (0.11%)). A statistically
      significant correlation was found between macrophage volume fraction and weight
      of proteinuria in minimal change nephropathy but not in membranous
      glomerulonephritis. Correlations were found in both diseases between macrophage
      volume fraction and serum creatinine at time of biopsy. CONCLUSIONS: The
      equipment is inexpensive and measurement takes less than one minute per biopsy
      specimen. The results indicate that macrophage infiltration is part of the
      pathological process in minimal change nephropathy and membranous
      glomerulonephritis. The correlation with creatinine at time of biopsy suggests
      that renal impairment in minimal change nephropathy may result from infiltration
      by immunologically active cells and not merely from haemodynamic changes in
      nephrons. However, the correlation is not close, indicating that the relation
      between macrophage infiltration and disease severity is not a simple one.

PMID- 9155692
TI  - Interstitial myofibroblasts: predictors of progression in membranous nephropathy.
AB  - AIMS: To determine the role of interstitial myofibroblasts in the progression of
      membranous nephropathy; and to assess the predictive value of quantifying
      myofibroblasts in determining long term renal outcome. METHODS: All cases of
      membranous nephropathy, diagnosed by renal biopsy at University Hospital of South
      Manchester between 1984 and 1987, were studied retrospectively. The biopsy
      specimens (n = 26) were reviewed and analysed morphometrically to measure
      interstitial volume as a proportion of the total volume of renal cortex, and
      numbers of interstitial myofibroblasts (cells positive for alpha-smooth muscle
      actin within the interstitium). Clinical data, with a follow up of seven to eight
      years, was available for 24 patients, and renal outcome was correlated with
      pathological changes in the initial diagnostic biopsy specimen. RESULTS: The
      number of myofibroblasts and interstitial volume were inversely correlated with
      creatinine clearance at the initial biopsy, and at the end of follow up.
      Percentage sclerosed glomeruli or stage of glomerular disease, assessed by
      electron microscopy, did not correlate with renal function at initial biopsy or
      during follow up. The number of myofibroblasts, but not interstitial volume,
      correlated with severity of proteinuria at initial biopsy. Of 15 biopsy specimens
      showing no or mild interstitial fibrosis, four showed a notable increase in the
      number of interstitial myofibroblasts. All of these patients developed chronic
      renal failure, compared with three of 11 patients whose specimens showed no or a
      mild increase in myofibroblast numbers. CONCLUSIONS: Interstitial myofibroblasts
      play a role in the development of interstitial fibrosis and progressive renal
      failure in membranous nephropathy. Increased numbers of myofibroblasts in biopsy
      specimens showing only mild fibrosis may predict subsequent chronic renal
      failure.

PMID- 9155693
TI  - Childhood non-Hodgkin lymphomas in the United Kingdom: findings from the UK
      Children's Cancer Study Group.
AB  - AIM: To review the presenting clinical features and the histology of cases of non
      Hodgkin lymphoma (NHL) entered into the United Kingdom Children's Cancer Study
      Group NHL Trial. METHODS: Sections of biopsy specimens from all cases entered
      into the trial were stained with Giemsa and haematoxylin and eosin. All cases
      were stained immunohistochemically for CD45, CD3, CD45RO, CD20, and CD30.
      Sections were stained with either naphthol AS-D chloroacetate esterase or KP1
      (CD68) to identify granulocytic tumours. In a minority of cases, additional
      immunohistochemical stains were performed when necessary to establish the
      diagnosis. The sections were reviewed by three pathologists. RESULTS: Of 308
      cases analysed, 293 were categorised as NHL. There was only one case of low grade
      lymphoma in the series. Over 80% of the cases fell into the categories Burkitt
      lymphoma (42.2%), lymphoblastic lymphoma (27.2%) and anaplastic large cell
      lymphoma (15.1%). Cases of Burkitt lymphoma presented most often with abdominal
      tumours mainly of the ileocaecal region. Tumours of the oropharynx and
      nasopharynx were also common in this group. Of the 84 lymphoblastic lymphomas, 56
      were of the T-cell phenotype, 12 of the B-cell phenotype and 16 of indeterminate
      lineage. Most of the T-lymphoblastic lymphomas showed mediastinal or pleural
      involvement. Infiltration of the skin and soft tissues was seen in 25% of
      lymphoblastic lymphoma of B or indeterminate phenotype. Forty six children were
      diagnosed as having anaplastic large cell lymphoma, the majority being of T or
      indeterminate lineage. Most patients presented with lymphadenopathy but
      involvement of the bones, soft tissues or skin was seen in seven patients and of
      the mediastinum and lungs in five. CONCLUSION: Childhood non-Hodgkin lymphomas
      are almost all high grade and frequently extranodal. They fall mainly into the
      categories Burkitt lymphoma, lymphoblastic lymphoma and anaplastic large cell
      lymphoma. The separation of these subcategories can be made on the basis of
      morphology and immunohistochemical features. The anatomical distribution of these
      different categories of non-Hodgkin lymphoma is distinctive.

PMID- 9155694
TI  - Co-localisation of insulin-like growth factor II and the proliferation marker
      MIB1 in hepatocellular carcinoma cells.
AB  - AIM: To assess the effect of insulin-like growth factor II (IGF-II) on
      proliferation of hepatocellular carcinoma (HCC) cells. METHODS: Expression of IGF
      II mRNA and protein was detected in 10 archival HCC specimens using in situ
      hybridisation and immunohistochemistry, respectively. Expression of the Ki-67
      antigen, a proliferation marker, was determined immunohistochemically on the same
      sections. RESULTS: Increased expression of IGF-II mRNA and protein was detected
      in five of the 10 HCCs in cells located at the periphery of tumour nests. The
      pattern of localisation of IGF-II was almost identical with that of Ki-67
      antigen. CONCLUSIONS: Most of the Ki-67 antigen positive cells co-expressed IGF
      II, suggesting that IGF-II may act as an autocrine or paracrine growth factor,
      and may play an important role in the development of HCC.

PMID- 9155695
TI  - Colorectal cancer pathology reporting: a regional audit.
AB  - AIMS: To audit the information content of pathology reports of colorectal cancer
      specimens in one National Health Service region. METHODS: All reports of
      colorectal cancer resection specimens from the 17 NHS histopathology laboratories
      in Wales during 1993 were evaluated against: (a) standards previously agreed as
      desirable by pathologists in Wales; and (b) standards considered to be the
      minimum required for informed patient management. RESULTS: 1242 reports were
      audited. There was notable variation in the performance of different laboratories
      and in the completeness of reporting of individual items of information. While
      many items were generally well reported, only 51.5% (640/ 1242) of rectal cancer
      reports contained a statement on the completeness of excision at the
      circumferential resection margin and only 30% (373/1242) of all reports stated
      the number of involved lymph nodes. All of the previously agreed items were
      contained in only 11.3% (140/1242) of reports on colonic tumours and 4.0%
      (40/1242) of reports on rectal tumours. Seventy eight per cent (969/1242) of
      colonic carcinoma reports and 46.6% (579/ 1242) of rectal carcinoma reports met
      the minimum standards. CONCLUSIONS: The informational content of many routine
      pathology reports on colorectal cancer resection specimens is inadequate for
      quality patient management, for ensuring a clinically effective cancer service
      through audit, and for cancer registration. Template proforma reporting using
      nationally agreed standards is recommended as a remedy for this, along with
      improved education, review of laboratory practices in the light of current
      knowledge, and further motivation of pathologists through their involvement in
      multidisciplinary cancer management teams.

PMID- 9155696
TI  - A novel quantitative immunoassay system for p53 using antibodies selected for
      optimum designation of p53 status.
AB  - AIM: To develop a highly sensitive and specific enzyme linked immunosorbent assay
      (ELISA) system for analysis of p53 protein in cancer lysates. METHODS: The anti
      p53 monoclonal antibodies DO7, 1801, BP53.12, and 421, and anti-p53 polyclonal
      antiserum CM1 were assessed by immunohistochemistry and western blot analysis to
      identify those most suitable for determining p53 status of cancer cells.
      Antibodies with desired characteristics were used to develop a non-competitive
      sandwich type ELISA system for analysis of p53 expression in cancer cytosols.
      Using the ELISA, p53 protein concentrations were measured in a small series of
      breast cancers, and the quantitative values compared with p53 immunohistochemical
      data of the same cancers. RESULTS: DO7 and 1801 gave the most specific and
      reliable results on immunohistochemistry and western blot analysis. Using these
      two antibodies, a non-competitive sandwich type ELISA system was developed to
      analyse p53 quantitatively. Analysis of the breast cancer series showed a good
      correlation between immunohistochemistry and the ELISA-tumours were generally
      positive using both techniques. Discrepancies were noted however: some cancers
      were immunohistochemically negative but ELISA positive. One explanation for this
      may be that the ELISA is more sensitive than immunohistochemistry. CONCLUSION:
      The p53 ELISA system is a non-competitive double monoclonal antibody sandwich
      method, using DO7 and 1801 which have been shown to be highly specific for p53
      protein by immunohistochemistry and western blot analysis. The lower threshold of
      the assay is 0.1 ng/ml analyte in an enriched recombinant p53 preparation. As p53
      is now regarded as a protein associated with prognosis in breast and other
      cancers, the assay may have clinical applications.

PMID- 9155697
TI  - Importance of cryptolytic lesions and pericryptal granulomas in inflammatory
      bowel disease.
AB  - AIMS: To explore the diagnostic importance of pericryptal granulomas associated
      with epithelial lysis in colorectal biopsy specimens (cryptolytic colitis).
      METHODS: A series of patients with suspected inflammatory bowel disease and
      colorectal biopsy specimens showing either isolated pericryptal granulomas (14
      cases) or non-granulomatous pericryptal inflammation (eight cases) were followed.
      A diagnosis of Crohn's disease was established if subsequent biopsy specimens or
      intestinal resections showed unequivocal non-crypt related granulomas, or if
      there was evidence of significant small bowel disease. RESULTS: Of the 14
      patients with pericryptal granulomas and biopsy specimens, 10 were subsequently
      found to have Crohn's disease; of the eight patients with pericryptal
      inflammation only, one developed Crohn's disease. The former group also had a
      much higher instance of morbidity and required surgical intervention more often.
      CONCLUSIONS: The presence of cryptolytic granulomas in a colorectal biopsy
      specimen otherwise showing only non-specific inflammatory changes should always
      raise suspicion of Crohn's disease, especially if surgery or ileo-anal pouch
      formation is contemplated.

PMID- 9155698
TI  - Comparative analysis of biotin intranuclear inclusions of gestational endometrium
      using the APAAP, ABC and the PAP immunodetection systems.
AB  - AIMS/BACKGROUND: Intranuclear inclusions have been observed in gestational
      endometrial glands. Although resembling Herpes simplex virus infected cells,
      these nuclei have been shown to contain endogenous biotin. Hence,
      immunohistochemical systems using the avidin-biotin complex will result in cross
      reaction and false positivity. This study investigates a series of 10 gestational
      endometria (formalin fixed and paraffin wax embedded) with intranuclear
      inclusions using three different immunodetection systems with primary anti
      biotin. RESULTS: Both the alkaline phosphatase anti-alkaline phosphatase (APAAP)
      and peroxidase anti-peroxidase (PAP) systems confirmed that the intranuclear
      inclusions were endogenous biotin. The streptavidin biotin complex (StreptABC)
      system produced a positive reaction in both test sections and controls (omitting
      primary anti-biotin) in the presence of prior blocking with free avidin and
      biotin. In addition, aberrant immunoreactivity was observed in adjacent
      nuclei/cytoplasm of endometrial glands and decidualised stroma in the negative
      control of the PAP system. This was subsequently eliminated using microwave
      pretreatment prior to immunohistochemistry. CONCLUSION: The use of either the
      APAAP or PAP immunodetection systems (the latter with microwave pretreatment) is
      recommended for any immunohistochemical or non-isotopic in situ hybridisation
      investigation undertaken on gestational endometria.

PMID- 9155699
TI  - Cerebrospinal fluid plasminogen activator inhibitor-1 in patients with
      neurological disease.
AB  - AIM: To study cerebrospinal fluid (CSF) concentrations of plasminogen activator
      inhibitor type-1 (PAI-1) in patients with neurological disease. METHODS: CSF PAI
      1 concentrations were measured in 51 patients with neurological disease and 20
      reference subjects using an ELISA. The patient group comprised three patients
      with viral meningitis, 20 with encephalitis, nine with acute lymphoblastic (n =
      7) and myeloid (n = 2) leukaemia (with central nervous system involvement), and
      19 with multiple sclerosis. RESULTS: Raised PAI-1 concentrations were observed in
      patients with leukaemia, encephalitis and multiple sclerosis. There was no
      difference in the mean concentrations of PAI-1 in patients with meningitis when
      compared with the reference subjects. The highest mean (SEM) PAI-1 concentration
      was found in patients with leukaemia (1.28 (0.36) ng/ml), and the next highest in
      those with encephalitis (1.19 (0.20) ng/ml). these values were much higher than
      those in patients with viral meningitis. In a previous report, raised CSF tissue
      type plasminogen activator (tPA) activities were detected in patients with
      multiple sclerosis, leukaemia and encephalitis, with mean activities in
      decreasing order. PAI-1 concentrations in the same patients were the reverse of
      their corresponding tPA activities, being higher in those with leukaemia and
      encephalitis, than in patients with multiple sclerosis. There was no association
      between CSF PAI-1 concentrations and age in either patients or controls.
      Similarly, there was no association between CSF PAI-1 concentrations and
      urokinase-type plasminogen activator (uPA). CONCLUSIONS: Raised CSF PAI-1
      concentrations may be used as a non-specific marker of neurological disease.
      Moreover, PAI-1 may play an important role in regulating the functions tPA, and
      probably uPA, in CSF.

PMID- 9155701
TI  - Comparison of commercial slide agglutination kits with a tube coagulase test for
      the rapid identification of Staphylococcus aureus from blood culture.
AB  - Eighty clinical specimens of BACTEC 9240 blood culture vials, culture positive
      for staphylococci (38 Staphylococcus aureus and 42 coagulase negative
      staphylococci), were tested directly for the presence of clumping factor/protein
      A and free coagulase. Seven commercial slide agglutination kits were compared
      with a direct-tube coagulase (DTC) method. All tests were performed on blood
      culture pellets. Sensitivity, specificity, and negative and positive predictive
      values for the seven commercial kits were extremely variable, whereas a two-hour
      DTC test was highly predictive of S aureus. There was no significant difference
      between a two-, six- or 24-hour DTC test. Three (8%) S aureus isolates remained
      DTC negative even after 24 hours' incubation. Staphylococcal slide agglutination
      kits should not be used directly on blood culture broths. In contrast, a two-hour
      DTC test is a useful, rapid screening test for S aureus bacteraemia, provided
      isolates from DTC negative blood culture broths are re-tested using standard
      laboratory techniques.

PMID- 9155700
TI  - Kawasaki disease, Epstein-Barr virus and coronary artery aneurysms.
AB  - AIM: To establish whether infection with Epstein-Barr virus (EBV) contributed to
      the development of coronary artery lesions in a six year old child with an
      aneurysm and stenoses of the coronary arteries and suspected Kawasaki disease.
      METHODS: Postmortem paraffin wax sections of the coronary artery and myocardium
      were examined by in situ hybridisation for expression of EBER-1 (EBV-encoded RNA
      1). Positive controls consisted of an EBV positive case of Hodgkin disease and a
      case of posttransplantation lymphoma. RESULTS: No EBER-1 positive cells were
      identified in either myocardium or walls of the coronary artery. CONCLUSIONS:
      Although EBV has been implicated in the aetiology of Kawasaki disease and
      development of coronary artery lesions, this process was not confirmed in this
      patient. It is likely that an unusual immunological reaction to a primary EBV
      infection with suspected deregulation of T helper cell activity leads to severe
      coronary artery damage in early childhood.

PMID- 9155702
TI  - Bone marrow granulomas in infiltrating lobular breast cancer.
AB  - A 50 year old woman with a history of infiltrating lobular breast carcinoma
      presented with back pain. Bone scan and magnetic resonance imaging were not
      conclusive. A bone marrow aspirate appeared normal. A routine trephine biopsy
      specimen showed granulomas but no obvious infiltration by carcinoma.
      Immunohistochemical staining with epithelial markers demonstrated carcinoma cells
      in the trephine specimen. This case illustrates the difficulty of detecting
      infiltrating lobular carcinoma in bone marrow and the value of immunological
      techniques in this context. It also describes the development of bone marrow
      granulomas as a response to infiltration by carcinoma.

PMID- 9155703
TI  - Leu-M1 immunoreactivity and phaeochromocytoma.
AB  - The aim was to evaluate Leu-M1 immunoreactivity as a prognostic factor in
      phaeochromocytoma. Anti-Leu-M1 monoclonal antibodies were used to determine the
      Leu-M1 immunoreactivity in 17 histologically confirmed phaeochromocytomas from 15
      patients, using an avidin-biotin technique. Ten patients had a sporadic
      phaeochromocytoma, and five had multiple endocrine neoplasia type 2A (MEN 2A).
      Malignancy was diagnosed in three patients by the presence of metastases. Leu-M1
      immunoreactivity was shown in 12 (70.5%) phaeochromocytomas. Three patterns of
      arrangement were observed: isolated (scattered positive cells) (n = 3); focal
      (aggregates of positive cells) (n = 5), and diffuse patterns (dispersed positive
      cells) (n = 4). Two cases of malignant phaeochromocytoma were positive (one focal
      and one isolated pattern). All cases of MEN 2A showed immunoreactivity, although
      no characteristic pattern was prevalent. A diffuse pattern was observed in all
      phaeochromocytomas longer than 7 cm. In conclusion, Leu-M1 expression is frequent
      in phaeochromocytoma. However, Leu-M1 immunoreactivity seems to be useless in
      predicting malignant behaviour and to be influenced mainly by tumour size.

PMID- 9155704
TI  - Endometrial ossification in a postmenopausal woman.
AB  - A case of endometrial ossification in a 62 year old woman is reported. The
      patient presented with increased vaginal discharge. On transvaginal
      ultrasonography, a hyperechoic area within the uterine cavity, suggestive of an
      intrauterine foreign body, was noted. Histological examination of the endometrial
      curettage showed mature bone with neutrophilic infiltration. There was no
      evidence of malignancy. Endometrial ossification in postmenopausal women is very
      rare; most women presenting with this condition are between 20 and 40 years of
      age. Therefore, clinicians should consider the possibility of endometrial
      ossification as a differential diagnosis of intrauterine foreign body on
      ultrasound, even in older patients. In addition, pathologists should be aware of
      this rare entity to avoid a misdiagnosis of malignant mixed mullerian tumor in
      the endometrial curettage specimen, which may result in unnecessary hysterectomy.

PMID- 9155705
TI  - Lithium associated autoimmune thyroiditis.
AB  - A case of autoimmune thyroiditis after long term treatment with lithium is
      described in a 29 year old Japanese woman with manic depression. Positive serum
      antithyroglobulin and antimicrosomal antibodies, diffuse goitre, and microscopic
      chronic thyroiditis, as well as the clinical history of long term lithium
      treatment were suggestive of lithium associated autoimmune thyroiditis.
      Microscopically, there was a mild degree of interstitial fibrosis and a moderate
      degree of lymphocytic infiltration. Some areas showed a moderate degree of
      stromal fibrosis and atrophic thyroid follicles. Lymphoid follicles with germinal
      centres, disrupted thyroid follicles with lymphocytic infiltration, and Hurthle
      cells were also observed. The differential diagnosis in patients presenting with
      these histological features includes painless (silent) thyroiditis, autoimmune
      thyroiditis and lithium associated autoimmune thyroiditis. A detailed clinical
      history is essential if the correct diagnosis is to be reached.

PMID- 9155707
TI  - Do HPV-negative cervical carcinomas exist?
AB  - Based on improvements in HPV detection technology, it appears that an almost 100%
      HPV association is reached for cervical cancer, as demonstrated in an
      accompanying paper in this issue of the Journal. Factors which may explain the
      rare cases in which no HPV DNA is detectable include: improper sampling;
      disruption of HPV by integration events; the existence of still unidentified
      HPVs; sensitivity of the method; and the mechanism of transformation. Finally,
      epidemiological studies identifying HPV independent risk factors are necessary to
      answer the question of whether HPV independent pathways exist for cervical
      carcinogenesis.

PMID- 9155706
TI  - Atypical manifestations in a patient with systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a chronic systemic inflammatory disease
      associated with the production of various autoantibodies and involvement of
      multiple organs. Necropsy findings in a 65 year old woman with SLE who had
      multiple aortic aneurysms and dissections, as well as other unusual
      manifestations, are described. The case illustrates the occurrence of and the
      difficulties encountered in the diagnosis of several diseases, namely aortic
      aneurysm, aortic dissection, acute pancreatitis, and Penicillium marneffei
      infection.

PMID- 9155708
TI  - The pathology of the ring-substituted amphetamine analogue 3,4
      methylenedioxymethylamphetamine (MDMA, 'Ecstasy')

PMID- 9155709
TI  - Cytokines and the hepatic acute phase response.
AB  - The acute phase response is an orchestrated response to tissue injury, infection
      or inflammation. A prominent feature of this response is the induction of acute
      phase proteins, which are involved in the restoration of homeostasis. Cytokines
      are important mediators of the acute phase response. Uncontrolled and prolonged
      action of cytokines is potentially harmful, therefore mechanisms exist which
      limit the activity of cytokines; these include soluble cytokine receptors and
      receptor antagonists. The cytokine signal is transmitted into the cell via
      membrane-bound receptors. Different intracellular signalling pathways are
      activated by different cytokine-receptor interactions. Eventually, cytokine
      inducible transcription factors interact with their response elements in the
      promotor region of acute phase genes and transcription is induced. Systemic
      inflammation results in a systemic acute phase response. However, local
      inflammatory or injurious processes in the liver may also induce an acute phase
      response, for example after partial hepatectomy and during hepatic fibrosis. The
      acute phase proteins induced in these conditions probably act to limit
      proteolytic and/or fibrogenic activity and tissue damage. The possible function
      of the acute phase protein alpha 2-macroglobulin in hepatic fibrosis is discussed
      in some detail.

PMID- 9155710
TI  - Cyclin D1 in mammary carcinoma.
AB  - The control of the cell-cycle-associated protein cyclin D1 and its variable
      behaviour in normal and transformed cells is described and contrasted with its
      activity in vivo. The role of cyclin D1 as a prognostic and predictive marker is
      examined in clinical breast cancer. High levels of the protein are seen in well
      differentiated, oestrogen receptor positive tumours, which respond well to
      tamoxifen treatment for metastatic disease.

PMID- 9155711
TI  - Human papillomavirus infection and invasive cervical neoplasia: a study of
      prevalence and morphology.
AB  - The prevalence of human papillomavirus (HPV) DNA sequences in 45 cervical cancer
      biopsies was examined with the hot-start polymerase chain reaction (PCR),
      employing HPV consensus primers from the L1 region. The cases comprised 38
      squamous cell carcinomas, three adenosquamous carcinomas, and four
      adenocarcinomas. PCR products were typed with single-strand conformation
      polymorphism (SSCP) and the HPV types detected were correlated with tumour type.
      Forty-three biopsies were HPV-positive, HPV16 being the most prevalent type.
      HPV18/33/45/58 were also detected, but no low-risk or multiple types.
      Keratinizing squamous cell carcinoma was invariably associated with HPV16 and
      adenosquamous carcinoma and adenocarcinoma with HPVs 18/45. Non-keratinizing
      squamous cell carcinomas harboured all five detected types. Our data corroborate
      the view that malignant cervical tumours are almost invariably associated with
      high-risk HPV and that certain malignant cervical tumour phenotypes correlate
      with specific HPV types.

PMID- 9155712
TI  - Human papillomavirus infection is not associated with bronchial carcinoma:
      evaluation by in situ hybridization and the polymerase chain reaction.
AB  - While a strong association between human papillomaviruses (HPVs) and squamous
      cell cancers of the female genital tract is known to exist, there is substantial
      controversy regarding the relationship of HPV with other non-genital carcinomas.
      Recently there have been some reports focusing on a possible association of HPVs
      with bronchial carcinomas. These studies mostly used either in situ hybridization
      (ISH) or the polymerase chain reaction (PCR). In view of these reports, 32
      squamous cell carcinomas (SCCs) and six small cell carcinomas of the bronchus
      were examined for the presence of HPV DNA by both techniques: ISH using 35S
      labelled, type-specific probes (HPV 6, 11, 16, 18), and PCR with consensus
      primers coding for more than 25 different HPV subtypes performed on formalin
      fixed, paraffin-embedded material. None of the 38 bronchial carcinomas analysed
      was positive for HPV DNA, either by ISH or by PCR. On the other hand,
      additionally examined specimens of 15 cervical carcinomas were positive for HPV
      16 DNA in at least three cases by ISH (20 per cent) and in 12 cases by PCR (80
      per cent). We conclude that common HPV types do not play an important role in the
      pathogenesis of bronchial carcinoma.

PMID- 9155713
TI  - Genetic heterogeneity in sporadic colorectal adenomas.
AB  - The majority of colorectal cancers develop from adenomatous polyps under the
      influence of factors that are still poorly understood. Tumourigenesis is
      generally considered a multistep process in which multiple genetic alterations
      occur, eventually reflected in abnormalities of the cellular DNA content.
      Macroscopical features such as tumour size and tumour architecture (tubular,
      tubulovillous, or villous) are correlated wit the chance of malignancy in the
      lesion. Grade of dysplasia can be considered an indicator for the level of
      progression of the adenoma towards invasive carcinoma. These characteristics were
      correlated with the presence or absence of K-ras mutations and the DNA ploidy in
      a prospective study performed on 46 large sporadic colorectal adenomas resected
      by endoscopy. DNA ploidy and K-ras mutations were analysed in two samples taken
      at distant sites in the adenomas. Aneuploidy was present in 12 adenomas (26 per
      cent) and K-ras mutations occurred in 26 (57 per cent). A highly significant
      correlation was found between aneuploidy and adenoma size, architecture, and
      grade of dysplasia. The presence of K-ras mutations was significantly correlated
      only with the size of the adenomas. The proportion of adenomas with aneuploidy
      and/or a K-ras mutation increased when two samples were analysed instead of one.
      This observation suggests that the prevalence of genetic mutations and of
      aneuploidy is probably underestimated, as generally only one sample is
      investigated. No correlation was observed between K-ras mutations and ploidy.
      This study demonstrates the presence of genetic heterogeneity in colorectal
      adenomas and supports the notion that K-ras mutation is an early event, while
      aneuploidy is a late event in the adenoma-carcinoma sequence.

PMID- 9155714
TI  - Expression of the 67 KD laminin receptor in human cervical preneoplastic and
      neoplastic squamous epithelial lesions: an immunohistochemical study.
AB  - Interactions of cancer cells with laminin play a critical role during the
      progression of solid malignant tumours. Increased expression of the 67 kD laminin
      receptor (67LR), one of the several laminin binding proteins, is associated with
      the invasive and metastatic capacity of various types of cancer, including
      breast, colon, ovary, lung, and endometrial carcinoma. In this study, 67LR
      expression was analysed in a series of cervical biopsy specimens including 16
      normal cervical tissues, 36 low-grade squamous intraepithelial lesions (SILs), 24
      high-grade SILs, and 11 invasive carcinomas. Detection of the 67LR was performed
      using immunoperoxidase staining and the monoclonal antibody MLuC5 which
      specifically recognizes the 67LR. Immunostaining of the 67LR was correlated with
      human papillomavirus (HPV) type detected by in situ hybridization and with
      proliferative activity of the lesion determined by immunohistochemistry with the
      MIB-1 monoclonal antibody, specific for the Ki67 antigen. Increased expression of
      the 67LR was correlated with the histological severity of the lesions, with the
      strongest immunoreactivity being found in invasive carcinomas. Significant
      differences in 67LR expression were found between normal cervical epithelium and
      high-grade SILs (P < 0.05, non-parametric Mann-Whitney test) or invasive
      carcinomas (P < 0.001), as well as between low- or high-grade SILs and invasive
      carcinoma (P < 0.01 and P < 0.05, respectively). Ki67 antigen expression also
      increased with the severity of the lesions. There was a positive correlation for
      each type of lesion between expression of the 67LR and of the Ki67 antigen. No
      specific relationship was found between 67LR or Ki67 antigen immunostaining and
      HPV type detected in SILs, segregated into low-grade and high-grade lesions.
      These data add weight to the evidence that increased expression of the 67LR is a
      consistent, but not sufficient feature of the invasive and metastatic phenotype
      and suggest that high expression of the 67LR might be associated with both more
      proliferative and more aggressive cervical (pre)neoplastic lesions.

PMID- 9155715
TI  - E-cadherin quantitative immunocytochemical assays in breast carcinomas.
AB  - The reduction of E-cadherin expression, which is involved in the initial step of
      invasion and metastasis of cancer, was investigated in 218 human breast
      carcinomas. Quantitative immunohistochemical assays (ICAs) were performed on
      frozen sections. Quantitation was assessed by processing digitized microscopic
      images of immunoreactions using a computerized system of image analysis (SAMBA).
      The results were correlated with clinicopathological data and quantitative
      immunodetection of other molecules. E-cadherin expression was significantly (P <
      0.001) stronger in ductal carcinomas than in lobular carcinomas and stronger (P <
      0.01) in low grades than in high grades, but E-cadherin was independent of lymph
      node status and tumour size. Also an inverse significant (P < 0.01) relationship
      was observed between E-cadherin expression on tissue sections and positive
      immunoreactions with anti-P53, MIB1 (growth fraction), and anti-c-erb-B2 product.
      Conversely, strong positive and anti-E-cadherin immunoreactions correlated with
      strong positive anti-ER and anti-PR immunoreactions (P < 0.01). No relationship
      was observed between E-cadherin and the results of quantitative ICAs of cathepsin
      D, CD31, and P-glycoprotein, assessed on consecutive sections from the same
      frozen tissue samples. The results show that preserved E-cadherin expression
      correlates with high degree of tumour differentiation, low proliferative
      activity, and low expression of prognostic markers. The deregulation of E
      cadherin is independent of other steps of tumour invasion, such as protease
      digestion of extracellular matrix and angiogenesis.

PMID- 9155716
TI  - Lack of expression of E-cadherin is associated with dissemination of Langerhans'
      cell histiocytosis and poor outcome.
AB  - Langerhans' cell histiocytosis (LCH) often occurs in children as a cutaneous
      disease. The course of the disease is characterized by either spontaneous
      resolution or multivisceral dissemination with poor prognosis. The pathogenesis
      of LCH is not known. Since E-cadherin mediates homophilic adhesion of normal
      Langerhans' cells to keratinocytes and is also a ligand of the alpha E beta 7
      intraepithelial lymphocyte integrin, this study was undertaken to investigate
      whether its expression on LCH cells correlates with the clinical behaviour of the
      disease. Clinical records of 14 children with LCH, all of whom had cutaneous
      involvement, were retrospectively analysed. The expression of E-cadherin was
      studied by in situ immunohistochemistry on 22 frozen biopsy samples with two
      specific monoclonal antibodies. LCH cells of the seven children with only skin
      involvement were positive for E-cadherin. By contrast, LCH cells of the seven
      children who further developed extensive LCH disclosed a negative or low
      expression of E-cadherin. This study shows that dissemination and poor prognosis
      are associated with lack of E-cadherin expression on LCH cells. Aggressive
      clinical evolution of LCH may therefore be related to the loss of functions
      mediated by E-cadherin.

PMID- 9155717
TI  - Localization and up-regulation of mucin (MUC2) gene expression in human nasal
      biopsies of patients with cystic fibrosis.
AB  - Using digoxigenin-UTP-labelled human HAM-1 (92 bp) or SMUC41 (850 bp) cRNA
      probes, the expression and localization of MUC2 gene transcripts were determined
      by in situ hybridization in human nasal tissues obtained as biopsies from 12
      patients with cystic fibrosis (CF): all had been part of a gene therapy trial in
      which CFTR cDNA-liposome complexes had been delivered by topical application to
      eight and liposome alone to four as a placebo control. For comparison, there were
      nasal tissues taken at surgical resection from four non-CF subjects and a further
      four biopsies taken from normal healthy volunteer controls. Both SMUC41 and HAM-1
      probes provided a strong signal. MUC2 mRNA transcripts were present in serous and
      mucous acini of submucosal glands, ciliated and basal cells of the surface
      epithelium, and occasional mononuclear inflammatory cells. The percentages (mean
      +/- SEM) of serous and mucous acini showing positivity for MUC2 gene expression
      in the four samples surgically resected from non-CF subjects were 25.4 +/- 5.6
      and 26.7 +/- 3.3 per cent, respectively. Compared with the non-CF subjects, the
      mean percentage of acini showing MUC2 gene expression in the four placebo-treated
      CF subjects was significantly higher for serous (80.5 +/- 12.7 per cent; P <
      0.05, t-test), but not for mucous acini (53.1 +/- 16.8 per cent; P = 0.38). In CF
      and non-CF groups, where present, MUC2 positivity was strongly expressed and
      constituted approximately 84 per cent of the cell area in serous acini, whereas
      it was less obvious and was confined to the perinuclear area of cells in mucous
      acini. A significantly greater proportion of the surface epithelium was positive
      for MUC2 mRNA transcripts in the CF subjects (89.0, +/- 1.4 per cent) than in the
      surgically resected tissues of the four non-CF subjects (19.4, +/- 4.0 per cent)
      (P = 0.02). In the eight CFTR-cDNA-treated subjects, there was an overall trend
      to reduction, but no statistically significant alteration of MUC2 gene
      expression. It is concluded that the MUC2 gene is expressed at three- to four
      fold higher levels in CF nasal mucosa than in non-CF nasal tissue and that it is
      expressed in a variety of cells additional to submucosal mucus-secreting glands.

PMID- 9155718
TI  - TAL-1 protein expression in vascular lesions.
AB  - The distribution of TAL-1 protein, an important vascular promoter in mice, has
      been examined immunohistochemically in a range of human vascular lesions and
      normal tissues. Formalin-fixed, paraffin-embedded vascular lesions including
      granulation tissue, haemangiomas, Kaposi's sarcomas, spindle cell
      haemangioendotheliomas, and angiosarcomas, were examined using a monoclonal
      antibody to recombinant TAL-1. Endothelial cells in all lesions gave positive
      immunostaining of variable intensity. Granulation tissue and spindle cell areas
      of the vascular tumours gave the strongest staining (nuclear and cytoplasmic).
      The better-differentiated endothelial cells within the tumours and resident well
      formed vessels were less positive and some cells were in fact negative. The
      malignant endothelial cells in angiosarcomas showed less intense positive
      staining than KS cells. This study has shown TAL-1 protein expression in a range
      of reactive, benign, and malignant vascular lesions. Protein expression appears
      to be stronger in the spindle cell areas, perhaps reflecting greater expression
      in less-differentiated endothelial cells.

PMID- 9155719
TI  - Apoptosis and proliferation (PCNA labelling) in CML--a comparative
      immunohistological study on bone marrow biopsies following interferon and
      busulfan therapy.
AB  - A comparative morphometric analysis was performed on smears and trephine biopsies
      of normal bone marrow and in chronic myelogenous leukaemia (CML) to assess the
      effects of therapy on apoptosis and cell proliferation. The in situ end-labelling
      (ISEL) technique was used for the demonstration of programmed cell death, in
      combination with the monoclonal antibody PG-M1 to identify macrophages. Cell
      proliferation was evaluated by employing the monoclonal antibody PC10 directed
      against proliferating cell nuclear antigen (PCNA). In CML (48 patients),
      significantly higher rates of apoptosis were observed than in normal bone marrow
      (smears, frozen sections, and paraffin-embedded samples) of 15 patients. In
      contrast, the PCNA labelling index of CML was not different from controls. In
      bone marrow tissue derived from CML patients, about 36 per cent of apoptotic
      bodies were ingested with CD68-positive macrophages. Study of the
      histotopographical distribution of labelled cells revealed that in CML, in
      contrast to the normal bone marrow, programmed cell death and PCNA activity were
      concentrated along the paratrabecular generation zone. In 28 patients with CML
      treated with interferon (IFN), sequential trephine biopsies displayed a
      significant enhancement of apoptosis which was associated with a decrease in PCNA
      reactivity. In contrast to this finding, no such alterations could be observed in
      24 patients who received busulfan (BU) monotherapy. This study furthers the
      understanding of cell kinetics in CML. IFN therapy induces apoptosis and
      suppresses cell proliferation. The rate of programmed cell death prior to therapy
      and the extent of IFN-triggered apoptosis exert a significant predictive impact
      on survival. In this study, ISEL-positive (apoptotic) cells and bodies do not
      correspond to unscheduled cell repair as detected by PCNA immunoreactivity.

PMID- 9155720
TI  - Tumour growth fraction and apoptosis in salivary gland acinic cell carcinomas.
      Prognostic implications of Ki-67 and bcl-2 expression and of in situ end
      labelling (TUNEL).
AB  - bcl-2 protein and Ki-67 (MIB-1) were studied in 32 acinic cell carcinomas (ACCs),
      all with a minimum of 5 years' clinical follow-up. Tumour apoptosis was evaluated
      by TdT dUTP nick end labelling (TUNEL) and by morphological criteria. Five
      patients died of their disease. Patients with stage I tumours had significantly
      better survival compared with other stages (P < 0.05). Patients with MIB-1
      negative tumours had significantly better survival than patients with MIB-1
      positive tumours (P = 0.05). This study confirms a previous report that MIB-1 is
      an independent prognostic factor for survival in patients with ACC. Stage I
      tumours had high expression of bcl-2 protein, but there was no difference when
      compared with other stages. TUNEL positivity was most prevalent in stage I
      tumours, compared with stages II, III, and IV (P < 0.05), probably indicating
      more apoptosis. This could imply a capacity of stage I tumours ('early tumours')
      for early selection of tumour cells for elimination by apoptosis. There was no
      significant difference between expression of bcl-2 and TUNEL, between these
      parameters and clinical outcome, or between any parameter and morphological
      subclassification. We conclude that MIB-1 has prognostic value in ACC. Clinical
      staging, bcl-2, and TUNEL are also potentially useful as prognostic markers.

PMID- 9155721
TI  - Extracellular matrix composition and integrin expression in early
      hepatocarcinogenesis in human cirrhotic liver.
AB  - Extracellular matrix (ECM) plays a major role in cell differentiation,
      proliferation, and gene expression, both in physiological and in pathological
      conditions. Immunohistochemistry has been used to investigate modifications of
      ECM and related receptors, the integrins, in 26 small nodular lesions developed
      in human cirrhotic livers, on the basis that these lesions could represent
      sequential steps of hepatocarcinogenesis: the lesions were 16 macroregenerative
      nodules (MRNs), either of ordinary (n = 5) or atypical (n = 11) type, and ten
      small (< 15 mm) hepatocellular carcinomas (HCCs). Data were compared with those
      obtained in the surrounding cirrhotic tissue, in large HCCs, and in normal liver.
      The results indicate similarities between ordinary MRNs and cirrhosis, on the one
      hand, and between atypical MRNs and small HCCs, on the other. Strong and
      homogeneous deposition of collagen type IV and laminin in sinusoids and
      overexpression of alpha 6 integrin by sinusoidal cells and hepatocytes were
      especially noticeable in dysplastic areas characteristic of atypical MRNs, as in
      small HCCs. In addition, the staining of alpha 2 and alpha 6 integrins in MRNs
      revealed the presence of widespread atypical ductular proliferation expanding
      from periportal and perinodular areas, containing epithelial cells with
      transitional (hepato-biliary) phenotype. These findings suggest a transition from
      atypical MRNs to small HCCs and a possible role for liver epithelial precursor
      cells ('stem cells') in the development and evolution of MRNs.

PMID- 9155722
TI  - Hypercoagulable state in a hypobaric, hypoxic environment causes non-bacterial
      thrombotic endocarditis in rats.
AB  - High-altitude hypoxia causes polycythaemia and a hypercoagulable state in humans
      and animals. This study examines the effects of a hypobaric, hypoxic environment
      (HHE) on the blood coagulation system in rats. A total of 170 male Wistar rats
      were housed in a chamber at the equivalent of 5500 m in altitude for 1-12 weeks.
      After 2 weeks of exposure to HHE, platelet counts decreased significantly; after
      4 weeks, the prothrombin and activated partial thromboplastin times were
      significantly prolonged, compared with those of control rats. In addition,
      individual coagulation factors (VII, IX, X, XI, and XII) were significantly
      decreased at 8 weeks (P < 0.05). Levels of anti-thrombin III and alpha 2-plasmin
      inhibitor also decreased (between 4 and 8 weeks). After 4-12 weeks of exposure to
      HHE, 30 of 56 rats (54 per cent) developed (i) non-bacterial thrombotic
      endocarditis (NBTE) or (ii) infarction of the myocardium or kidney, or both (i)
      and (ii). The incidence of NBTE increased from 33 per cent (5/15 rats) at 4 weeks
      to 100 per cent (7/7 rats) at 12 weeks. Electron microscopy showed detached
      endothelial cells in the mitral valves at 1 week; platelets adhered to the
      subendocardial matrix and platelet aggregation with thrombus formation was seen
      at 2 weeks of exposure. The results suggest that exposure to HHE induces a
      hypercoagulable state and causes an NBTE in rats that may result in consumption
      coagulopathy.

PMID- 9155723
TI  - Potential early markers of carcinogenesis in the mucosa of the head and neck
      using exfoliative cytology.

PMID- 9155724
TI  - Relationship between the expression of p53 and the aggressiveness of gastric
      carcinoma.

PMID- 9155725
TI  - Sampling follicular fluid without altering follicular status in cattle:
      oestradiol concentrations early in a follicular wave.
AB  - A transvaginal, ultrasound-guided in situ technique was developed for sampling
      follicular fluid from 6.0-12.5 mm follicles in cattle, with minimal interference
      with the subsequent development of the sampled follicle. Each follicle was
      sampled only once and the status of the follicle (future dominant or subordinate)
      was determined retrospectively. A sample (20 microliters) was successfully
      obtained from 77% of 132 targeted follicles. Reasons for considering an attempt
      unsuccessful were as follows: (1) ovaries difficult to manipulate in two heifers
      (eight follicles), (2) samples contaminated with blood (11 samples), and (3)
      follicles sampled but the antrum subsequently developed an apparent blood clot
      (11 follicles). Only the 102 successful collections were used in the statistical
      analyses for evaluating oestradiol concentrations in the follicular fluid and the
      follicle growth profiles before and after sampling. The follicles were sampled
      once on days 1, 2, 3, or 4 after the emerging dominant follicle was 4 mm in
      diameter. On day 1, there were no differences in the oestradiol concentrations
      among follicles that later became the dominant follicle, largest subordinate
      follicle, or smaller subordinate follicles (means for diameters, 6.7-6.9 mm;
      means for oestradiol, 30-42 ng ml-1). The mean diameter of the dominant follicle
      increased linearly over the 4 days. Concentrations of oestradiol in the dominant
      follicle increased curvilinearly, resulting from a slower increase between days 1
      (mean, 42 ng ml-1) and 2 (110 ng ml-1) than between days 2 and 3 (313 ng ml-1)
      and 3 and 4 (554 ng ml-1). Neither mean diameter nor mean oestradiol
      concentration of the largest subordinate follicle increased after day 2. Data
      were available from 19 follicular waves in which both the dominant and largest
      subordinate follicles were sampled on the same day. Oestradiol concentrations
      were not higher in the dominant follicle than in the largest subordinate follicle
      until the day after the two follicles began to deviate in growth rates (mean day
      of deviation, 2.5 +/- 0.2 days after emergence). These observations indicate that
      the future dominant follicle cannot be identified reliably by either its diameter
      or oestradiol production before the deviation in growth rates between the two
      largest follicles.

PMID- 9155726
TI  - Induction of early pregnancy factor activity in vitro by platelet-activating
      factor in mice.
AB  - The rosette inhibition test was used to determine early pregnancy factor activity
      in culture media from oestrous mouse ovaries and oviducts stimulated in vitro for
      early pregnancy factor production under different experimental conditions. Embryo
      conditioned media, platelet-activating factor and cortical granule release media
      could all stimulate the production of early pregnancy factor by oestrous mouse
      ovaries and oviducts. This stimulation was completely blocked by the presence of
      BN 52021, a platelet-activating factor receptor antagonist. This study indicates
      that platelet-activating factor is the 'ovum factor' released by the zygote on
      fertilization to initiate the synthesis of early pregnancy factor.

PMID- 9155727
TI  - Effects of space flight on ovarian-hypophyseal function in postpartum rats.
AB  - The effect of space flight in a National Aeronautics and Space Administration
      (NASA) shuttle was studied in pregnant rats. Rats were launched on day 9 of
      gestation and recovered on day 20 of gestation. On day 20 of gestation, rats were
      unilaterally hysterectomized and subsequently allowed to go to term and deliver
      vaginally. There was no effect of space flight on pituitary and ovary mass
      postpartum. In addition, space flight did not alter healthy and atretic ovarian
      antral follicle populations, fetal wastage in utero, plasma concentrations of
      progesterone and luteinizing hormone (LH) or pituitary content of follicle
      stimulating hormone (FSH). Space flight significantly increased plasma
      concentrations of FSH and decreased pituitary content of LH at the postpartum
      sampling time. Collectively, these data show that space flight, initiated during
      the postimplantation period of pregnancy, and concluded before parturition, is
      compatible with maintenance of pregnancy and has minimal effects on postpartum
      hypophyseal parameters; however, none of the ovarian parameters examined was
      altered by space flight.

PMID- 9155728
TI  - Ligand specificity of uterine oestrogen and progesterone receptors in the
      subadult African elephant, Loxodonta africana.
AB  - The ligand specificity of progesterone and oestrogen receptors in the uteri of
      four nonpregnant, nonlactating African elephants, killed during routine culling
      in the Kruger National Park, were determined. The mean (+/-SEM) Kd values of the
      oestrogen (0.18 +/- 0.019 x 10(-9) mol l-1, n = 12) and progesterone (0.22 +/-
      0.025 x 10(-9) mol l-1, n = 12) receptors were essentially similar when
      [3H]promegestone was used as radioligand in the progesterone receptor assays.
      However, when [3H]progesterone was used as radioligand, the progesterone receptor
      exhibited a significantly higher Kd value (1.03 +/- 0.132 x 10(-9) mol l-1, n =
      12) than that of the oestrogen receptor. The use of the different radioligands
      did not significantly affect the quantitative values obtained for the
      progesterone receptor. Both the oestrogen and the progesterone receptors
      displayed a high ligand specificity. The 5 alpha-reduced metabolites of
      progesterone exhibited a high relative binding affinity for the progesterone
      receptor (5 alpha-pregnane-3,20-dione: relative binding affinity = 43%; 5 alpha
      pregnane-3 alpha-ol-20-one: relative binding affinity = 20%) but the synthetic
      antiprogestin RU 486 did not compete successfully with progesterone in
      competitive binding studies. However, norethindrone (relative binding affinity =
      293%) competed successfully for binding to the progesterone receptor, and may
      have some potential in the future development of a technique to control
      reproductive output in the African elephant.

PMID- 9155729
TI  - The influence of the anti-androgen flutamide on early sexual differentiation of
      the marsupial male.
AB  - The development of the prostate and the normal descent of the testes in the
      tammar wallaby (Macropus eugenii) were influenced by treatment with the non
      steroidal anti-androgen flutamide. Male pouch young were treated daily from day 9
      to day 45, or from day 20 to day 45, of pouch life. Prostate development was
      inhibited in both treatment groups to a similar extent. Since prostatic buds do
      not form until day 25 of pouch life, these results suggest that there is a window
      of androgen sensitivity operating between day 20 and day 25 of pouch life. The
      number of prostatic buds was significantly lower, but despite the duration of
      treatment there was never complete abolition of prostate development. Although
      testes had descended to the same position in treated and control pouch young,
      inguinal hernias developed in three of four animals treated with flutamide from
      day 9. These data demonstrate that virilization of the male reproductive tract in
      this marsupial is dependent on a relatively brief exposure to androgens. Blocking
      androgen receptor action interferes with normal development of the inguinal
      canal, which suggests that it is this aspect of inguinoscrotal testicular descent
      that is androgen dependent.

PMID- 9155730
TI  - Detection of mRNA and immunoreactive proteins for acidic and basic fibroblast
      growth factor and expression of the fibroblast growth factor receptors in the
      bovine oviduct.
AB  - The heparin-binding acidic and basic fibroblast growth factors (aFGF, bFGF) and
      their receptors in the bovine oviduct are described. By means of western blot
      analysis one 18 kDa aFGF and two bFGF proteins (16 and 18 kDa, respectively) were
      detected in oviductal flushings. Different concentrations of these two growth
      factors could be measured in oviductal flushings during the oestrous cycle:
      concentrations of aFGF protein were significantly higher at ovulation (mean +/-
      SEM; 5.3 +/- 0.5 ng ml-1) than during the luteal phase (3.0 +/- 0.3 ng ml-1);
      concentrations of bFGF were higher at the preovulatory stage (3.5 +/- 0.7 ng ml
      1) than at the post-ovulatory stage (1.3 +/- 0.15 ng ml-1). Immunohistochemical
      studies using a/bFGF-specific antibodies indicated that these growth factors were
      localized mainly in oviduct epithelial cells. The sequence of the bovine FGF
      receptor (FGFR) was partly determined. Quantification of mRNAs by an RNase
      protection assay (RPA) showed that expression of aFGF and bFGF was different
      during the oestrous cycle, indicating that the regulation of aFGF is separate
      from that of bFGF. Only mRNA encoding bFGF and FGFR could be detected in cumulus
      oocyte complexes by reverse transcription PCR. In summary, the components of the
      FGF system were found in the bovine oviduct suggesting an autocrine or paracrine
      regulation involving oviduct cells and cumulus-oocyte complexes.

PMID- 9155731
TI  - Transient polyadenylation of a maternal mRNA following fertilization of mouse
      eggs.
AB  - The molecular basis for the recruitment of maternal mRNAs after fertilization is
      poorly understood, since there is little information available regarding the
      identity of such mRNAs. An assay based on reverse transcriptase and PCR was used
      to identify a maternal mRNA that undergoes a transient polyadenylation after
      fertilization; the length of the poly(A) tail increases from 40-80 adenosine (A)
      residues in the unfertilized egg to approximately 250 3 h after insemination and
      then decreases to about 180 around the time of pronucleus formation, that is 7 h
      after insemination. The DNA sequence of this cDNA, which encodes the
      polyadenylation signal AAUAA, contains a uridine-rich sequence that may serve as
      the cytoplasmic polyadenylation element observed in other maternal mRNAs that are
      recruited after fertilization.

PMID- 9155732
TI  - Prolactin-induced termination of obligate diapause of mink (Mustela vison)
      blastocysts in vitro and subsequent establishment of embryonic stem-like cells.
AB  - The mink reproductive cycle includes an obligatory period of embryonic diapause
      and delayed implantation, which continues in vitro and reduces the efficiency of
      embryonic stem (ES) cell establishment. Blastocysts recovered on day 7 and on
      days 13-16 after final mating were cultured in Dulbecco's modified Eagle's medium
      (DMEM) supplemented with various concentrations of prolactin to determine optimal
      conditions for embryo attachment and subsequent establishment of embryonic stem
      cells. Five treatments were applied to both ages of blastocyst: A, DMEM control
      (n = 16); B, DMEM + 5 micrograms prolactin ml-1 after 10 days initial culture in
      DMEM alone (n = 17); after 1 day of initial culture: C, DMEM + 10 ng prolactin ml
      1 (n = 17); D, DMEM + 1 microgram prolactin ml-1 (n = 19); and E, DMEM + 5
      micrograms prolactin ml-1 (n = 17). Prolactin terminated diapause of day 13-16
      blastocysts at all concentrations tested. The maximum attachment of embryos in
      vitro and subsequent production of ES-like cells occurred in medium supplemented
      with 5 micrograms prolactin ml-1. Prolactin did not affect attachment rates for
      day 7 blastocysts when 5 micrograms prolactin ml-1 was added, but prolactin at
      concentrations of 1 microgram ml-1 and 5 micrograms ml-1 when added on day 1 of
      culture enhanced ES-like cell line establishment. Two principal cell types were
      observed in the colonies: small stem cells and trophoblast-like cells with large
      areas of cytoplasm. The morphological evaluation of mink ES-like cell colonies
      was confirmed by cytochemical staining for alkaline phosphatase. Mink embryonic
      stem-like cells were found to stain positive for alkaline phosphatase. Alkaline
      phosphatase activity was lost upon cellular differentiation.

PMID- 9155734
TI  - Induction of cortical granule exocytosis of pig oocytes by spermatozoa during
      meiotic maturation.
AB  - Pig oocytes were examined to test their ability to undergo cortical granule
      exocytosis upon penetration by spermatozoa during meiotic maturation. Immature or
      maturing oocytes (cultured in vitro for 0 h, 26 h and 46 h) were inseminated with
      ejaculated boar spermatozoa in vitro. Before and after insemination, oocytes were
      stained with peanut agglutinin labelled with fluorescein isothiocyanate and the
      cortical granule distributions were examined under the fluorescent microscope and
      the laser confocal microscope. Before insemination, all the oocytes at the
      germinal vesicle stage showed a uniform distribution of cortical granules
      throughout the cortical cytoplasm. The granules migrated centrifugally during
      maturation and were distributed just beneath the oolemma in the oocytes after
      germinal vesicle breakdown, forming a monolayer in metaphase I or metaphase II.
      Cortical granules were still present in all penetrated oocytes at the germinal
      vesicle stage 18 h after insemination; in contrast, 26% and 84% of the oocytes
      inseminated at the stages of germinal vesicle breakdown or at metaphase I and II,
      respectively, completely released their cortical granules. Nuclear activation
      rates of penetrated oocytes were 0%, 38% and 96% in oocytes cultured for 0 h, 26
      h and 46 h, respectively. Of the nuclear-activated oocytes, 67% (oocytes cultured
      for 26 h) and 88% (oocytes cultured for 46 h) released cortical granules
      completely. Complete cortical granule exocytosis was not observed in nuclear
      inactivated oocytes. Of the nuclear-activated oocytes, 67% (oocytes cultured for
      26 h) and 80% (oocytes cultured for 46 h) of monospermic oocytes and 67% (oocytes
      cultured for 26 h) and 91% (oocytes cultured for 46 h) of polyspermic oocytes
      released cortical granules, and no statistical difference was observed between
      oocytes cultured for 26 h or 46 h, or between monospermic and polyspermic
      oocytes. The proportion of oocytes with cortical granule exocytosis increased as
      insemination time increased and was greatest 18 h after insemination in oocytes
      cultured for 26 h and 46 h; no obvious changes were observed when the
      insemination time was prolonged to 24 h. These results indicate that pig oocytes
      develop the ability to release cortical granules after penetration by spermatozoa
      following germinal vesicle breakdown, and that this ability is not fully
      developed until metaphase II. Cortical granule exocytosis is accompanied by
      nuclear activation, suggesting that both nuclear and cytoplasmic maturation are
      responsible for the cortical reaction. Polyspermy may be a result of a complete
      failure of cortical granule exocytosis in immature oocytes and delayed CG
      exocytosis in matured oocytes.

PMID- 9155733
TI  - Effect of immunization of rams against bovine inhibin alpha 1-26 on semen
      characteristics, scrotal size, FSH, LH and testosterone concentrations.
AB  - The effects of inhibin immunization on inhibin antibody titres, semen
      characteristics, scrotal size, fertility, FSH, LH and testosterone concentrations
      were determined by immunizing adult rams against bovine inhibin alpha 1-26-Gly
      Tyr conjugated to human serum albumin (n = 16) in non-ulcerative Freund's
      adjuvant and DEAE:dextran (1:1) or adjuvant alone (n = 16) on days 0 (29 June),
      30, 60, 191, 303 and 394. Blood samples were collected and bovine inhibin alpha 1
      26-Gly-Tyr antibody titres and serum testosterone concentrations were determined.
      Each month, between days 174 and 417, semen was collected every 30 min to a
      maximum of 15 ejaculates over 7 h and scrotal circumference was measured. Ram
      fertility was recorded during natural service. FSH, LH and testosterone
      concentrations and GnRH-induced FSH and LH release were measured in a subgroup of
      immunized (n = 5) and control (n = 5) rams at frequent intervals. Antibody titres
      were variable among immunized rams (0-46% 125I-labelled bovine inhibin alpha 1-26
      Gly-Tyr at 1:1600 serum dilution) but mean titres were consistently higher than
      in control rams (P < or = 0.001). Immunization did not alter the semen volume,
      output or quality of spermatozoa or ram fertility, but increased the mean scrotal
      circumference (37.6 +/- 0.8 cm versus 34.4 +/- 0.7 cm, P < 0.001). Mean FSH
      concentrations were higher in immunized rams during two intensive blood sampling
      periods (in June and August) (5.8 +/- 0.7 ng ml-1 versus 3.0 +/- 0.3 ng ml-1, P <
      0.001 in June; and 4.8 +/- 0.9 ng ml-1 versus 2.0 +/- 0.3 ng ml-1, P < 0.02 in
      August), and were correlated with antibody titres (r2 = 0.3, P < 0.05 in June;
      and r2 = 0.8, P < 0.001 in August). Discrete FSH pulses were not detected.
      Immunization did not alter mean or basal testosterone or LH concentrations, or LH
      pulse frequency; LH pulse amplitude was increased (1.6 +/- 0.2 ng ml-1 versus 0.8
      +/- 0.2 ng ml-1, P < 0.02) and was correlated with antibody titres (r2 = 0.6, P <
      0.01). Immunization enhanced GnRH-induced FSH (P < 0.05) but not LH release. In
      conclusion, immunization of adult rams against bovine inhibin alpha 1-26 Gly-Tyr
      increased scrotal circumference, mean FSH concentrations and LH pulse amplitude,
      without altering semen characteristics, fertility, mean LH concentrations, LH
      pulse frequency or mean testosterone concentrations.

PMID- 9155735
TI  - Alteration of testicular response to long photoperiod by transient exposure to
      short photoperiod in collared lemmings (Dicrostonyx groenlandicus).
AB  - The reproductive response of collared lemmings (Dicrostonyx groenlandicus) to
      photoperiod is unique for rodents. Whereas most reproductively photoresponsive
      rodents show maximal gonadal growth when exposed to long photoperiod (long day),
      collared lemmings show delayed maturation when born and maintained under this
      condition. However, transfer of lemmings from short photoperiod (short day) to
      long day results in maximal gonadal growth, indicating that the response to long
      day depends upon photoperiod history. We hypothesized that the slowing of
      maturation observed in animals born and maintained on long day reflects an
      inability to respond fully to long day, resulting from the absence of previous
      exposure to short day. To determine whether young lemmings born in long day are
      capable of being stimulated by long day, we exposed them at weaning (19 days of
      age) to 1, 6 or 10 weeks of short day, and then challenged them with a second
      exposure to long day. Relative to animals transferred permanently to short day at
      weaning, lemmings exposed to 6 weeks of short day showed accelerated gonadal
      growth after both 5 and 10 weeks of subsequent exposure to long day, and those
      exposed to 10 weeks of short day had larger testes after 6 weeks of long day.
      Thus, during transient exposure to short day, the animals acquired sensitivity to
      the stimulatory effects of long day. The responses of body mass, bifid claw width
      and pelage colour to the photoperiod manipulations did not parallel that of the
      gonads, indicating independent regulation of somatic and reproductive parameters.
      The unique way in which the reproductive system of collared lemmings responds to
      photoperiod may reflect evolution in an environment where the production of
      offspring during periods of unchanging long day (for example, the Arctic summer)
      is not selectively advantageous.

PMID- 9155736
TI  - Patterns of secretion of GnRH, LH and FSH during the postovulatory period in
      mares: mechanisms prolonging the LH surge.
AB  - To study the mechanisms responsible for the unusually slow decline of the
      ovulatory LH surge in mares, secretion patterns of GnRH, LH and FSH were
      monitored in pituitary venous blood collected every 2 or 5 min for 10.5-18.0 h
      from five mares on the third (n = 4) or fifth day after ovulation (first sampling
      period). To determine the effectiveness of progesterone negative feedback, mares
      were then given a luteolytic dose of a prostaglandin analogue (PGF2 alpha) and
      pituitary venous sampling (every 2 or 5 min for 16 h) recommenced 20-22 h later
      (second sampling period). During the declining arm of the LH surge, large peaks
      (detected by the Cluster algorithm) of concurrent LH and FSH secretion occurred
      infrequently, with four peaks being detected in a combined sampling period of 75
      h. Outside the peaks, LH or FSH secretion continued (as assessed by a pituitary
      to jugular-venous concentration ratio > or = 1.25) during 46% +/- 13 or 40% +/-
      10, respectively, of the sampling period. GnRH immunoactivity was detected during
      each spontaneous gonadotrophin peak, but at other times was generally at assay
      sensitivity. After PGF2 alpha, plasma progesterone fell (ng ml-1, mean +/- SEM;
      first sampling period: 8.6 +/- 0.8; second; 2.0 +/- 0.3; P = 0.001) and the
      frequency of LH (P < 0.05) and FSH (P < 0.02) peaks rose, with 28 peaks detected
      for each hormone in a total of 80 h sampling. Peaks in LH were smaller during the
      second period, with decreases observed in maximum (P = 0.027) and mean (P =
      0.025) secretion rates. Maximum GnRH secretion rate during peaks also declined (P
      = 0.010); however, the decrement (-30 +/- 6%) was less than that in maximum LH
      secretion rate (-82 +/- 5%; P = 0.040), suggesting that other factors contribute
      to the reduced LH peak amplitude. In summary, gonadotrophin peak frequency during
      the downswing of the surge in mares is slow, as in the midluteal phase, and the
      slow rate of decline in peripheral gonadotrophin concentrations is due, at least
      in part, to continued secretion between pulses. Moreover, progesterone negative
      feedback is highly effective in early dioestrus, in that lessening it without
      complete removal markedly accelerates gonadotrophin pulse frequency.

PMID- 9155737
TI  - Phenotype and maturation rate of oocytes of chimaeric mice produced from two
      strains that differ in oocyte quality.
AB  - The oocytes of females from the inbred mouse strains KE (albino) and CBA (agouti)
      differ in the following characteristics: the appearance of the cytoplasm is clear
      in KE but granular in CBA; the cumulus oophorus dispersion with hyaluronidase is
      quick in KE but slow in CBA; dissolution of the zona pellucida with a proteolytic
      enzyme is slow in KE but quick in CBA; and the maturation stage at the time of
      ovulation is metaphase I in KE while in CBA the first polar body has been
      extruded. Aggregation chimaeras were produced to investigate whether these
      differences are intrinsic or extrinsic to developing oocytes. Among 13 fertile
      chimaeric females, two produced only CBA oocytes, four produced both CBA and KE
      oocytes and were germline chimaeras, and seven produced only KE oocytes, as
      recognized by progeny testing. The larger number of females producing KE oocytes
      is a result of strong selection against CBA germ cells. All chimaeric females had
      cumuli composed of both KE and CBA cells, as recognized by the time of dispersion
      and glucose phosphate isomerase electrophoresis, but the presence of non
      homologous cumulus cells did not change the character of the developing oocytes
      significantly. The conclusion from this study is that the rate of meiotic
      maturation, sensitivity of oocyte investments to enzymes, and deposition of
      granules in ooplasm are determined largely autonomously by genes acting in the
      germ cells.

PMID- 9155738
TI  - Leukaemia inhibitory factor in endometrium during the oestrous cycle, early
      pregnancy and in ovariectomized steroid-treated ewes.
AB  - Leukaemia inhibitory factor (LIF), a pleiotropic cytokine, is essential for
      blastocyst implantation in mice and maintains the development of ovine embryos in
      culture. The expression of LIF was examined by northern blot analysis in
      endometrial tissue from cyclic (days 4-16) and pregnant (days 4-20) ewes, and the
      corresponding protein was immunolocalized. Expression of mRNA encoding LIF
      remained relatively constant throughout the oestrous cycle and was present during
      early pregnancy. A decrease in mRNA encoding LIF was observed during early
      pregnancy (on days 12-14) and expression was highest on days 16-20.
      Immunoreactive LIF was present in the cellular compartments of the endometrium
      throughout the oestrous cycle and early pregnancy, with maximal immunostaining in
      the caruncular and intercaruncular luminal epithelium, and moderate staining in
      the glandular epithelium and intercaruncular stroma. Immunoreactive LIF was also
      detected in the trophoblast cells of day 17 blastocysts. Separately cultured
      endometrial epithelial and stromal cells from pregnant animals both expressed
      mRNA encoding LIF. Ovariectomized steroid-treated ewes were studied to establish
      whether steroid hormones had a role in regulating endometrial LIF. Ewes treated
      with oestradiol alone showed lower concentrations of immunoreactive LIF in the
      endometrium in comparison to ovariectomized, control animals, while treatment of
      ovariectomized animals with both oestradiol and progesterone had a greater
      inhibitory effect on LIF immunolocalization. These studies demonstrate the
      presence of mRNA encoding LIF and protein throughout the oestrous cycle and early
      pregnancy and suggest that steroid hormones may be involved in their regulation.

PMID- 9155740
TI  - A survey of reproductive parameters in the free-ranging chimpanzees of Gombe
      National Park.
AB  - This study is a review of reproductive records for chimpanzees (Pan troglodytes
      schweinfurthii) living in Gombe National Park, Tanzania, between 1964 and 1994.
      Females exhibited their first full anogenital swelling at approximately 10.8
      years of age. Duration of adolescent infertility averaged 2.37 years, with first
      conception occurring at 12.7 years and first parturition at 13.3 years. The
      menstrual cycles of young nulliparous females were significantly longer than
      those of older multiparous females (average 39.8 days versus 33.8 days). Analysis
      of anogenital swelling patterns indicated an average duration of 12-13 days for
      maximal swelling in all classes of cycle. Nulliparous and postpartum females
      exhibited a similar pattern of shortened detumescent phase, indicative of
      anovulation. Duration of gestation averaged 225.3 days (range = 208-235) with no
      significant fetal gender effect. When an infant lived to weaning age, the
      postpartum amenorrhoea of the mother averaged 3.86 years, whereas if the
      offspring died as an infant the mother resumed menstrual cycles an average of 35
      days later. Once postpartum cycles resumed, the next conception averaged 142.5
      days later if the previous infant had survived, but sooner (92.9 days later) if
      the previous offspring died in infancy. Interbirth interval averaged 5.15 years.
      Analysis of behavioural records indicated that a lower percentage of conceptions
      occurred during consort matings than was previously thought, suggesting
      additional research is needed on this topic. Detailed discussion focuses on the
      environmental influence on reproductive parameters described here. Future work in
      this area will probably identify the importance of diet-via basic nutrition and
      phytochemical content-in effecting the seasonal and individual differences seen
      in this study.

PMID- 9155741
TI  - The role of albumin in the release of platelet-activating factor by mouse
      preimplantation embryos in vitro.
AB  - Platelet-activating factor (PAF) produced by embryos remained associated with
      mouse four-cell embryos after culture in vitro and was also released into the
      medium. The release of PAF into medium required albumin as a media supplement and
      the amount of PAF released increased (P < 0.05) with increasing albumin
      concentration. There was a trend for the amount of PAF remaining associated with
      embryos to decrease as the extracellular albumin concentration increased. The
      association of released PAF with albumin was confirmed by size fractionation with
      size exclusion membranes and high performance gel filtration, and by affinity
      chromatography (Cibacron blue and anti-BSA) and native PAGE. PAF released from
      embryos was not degraded by serum PAF:acetylhydrolase (PAF:AH; E.C. 3.1.1.47)
      after exposure for 24 h to the serum in vitro, while an equivalent concentration
      of synthetic PAF added to identical media was readily degraded, suggesting that
      PAF released from the embryo was protected from PAF:AH action. However, when the
      medium was subjected to organic extraction by the Bligh-Dyer
      (methanol/chloroform) method and the resulting extract added to equivalent media,
      embryo-derived PAF was readily degraded by PAF:AH. Furthermore, PAF in embryo
      conditioned medium (30 two-cell embryos for 24 h) could not be detected after
      direct assay of the culture medium by radioimmunoassay or bioassay (platelet
      aggregation in vitro), yet after extraction, purification and addition to medium
      with BSA, the embryo-derived PAF was readily detected in either assay. To
      determine whether the different behaviour of synthetic PAF and embryo-derived PAF
      resulted from differences in the nature of their binding to albumin, the location
      to which PAF bound was assessed by limited proteolytic digestion of albumin.
      Digestion with pepsin or trypsin showed that embryo-derived PAF was located
      exclusively between amino acids 240 and 386 (domain II) of albumin. Most
      synthetic PAF added to equivalent medium not exposed to embryos was not at this
      location, suggesting that PAF released from embryos bound to a site on albumin
      not generally accessible to synthetic PAF added to similar media.

PMID- 9155739
TI  - The role of a cAMP-dependent pathway in the uterine relaxant action of relaxin in
      rats.
AB  - The aim of this study was to investigate the role of the adenylyl cyclase
      pathway, and in particular cyclic AMP-dependent protein kinase A, in the relaxant
      action of relaxin in the isolated uterus of the nonpregnant rat. The purportedly
      selective inhibitor of cAMP-dependent protein kinase A N-[2-(methylamino) ethyl]
      5-isoquinolinesulfonamide hydrochloride (H-8) (at 100 mumol l-7) antagonized
      relaxin, salbutamol (an agonist at beta-adrenoceptors) and levcromakalim (a K+
      channel opener) to a similar extent (by factors of 3.1, 1.9 and 2.8,
      respectively), demonstrating that it is not a selective inhibitor. Relaxin and
      levcromakalim were less potent and had smaller, maximal, relaxant effects in
      longitudinal myometrium than in intact uterus cut in the longitudinal plane. By
      contrast, nifedipine (a Ca2+ channel blocker) was equipotent in the two
      preparations and salbutamol only slightly less potent in the longitudinal
      myometrium. Relaxin did not alter the cyclic AMP-dependent protein kinase A
      activity ratio in longitudinal myometrium, but did increase the activity ratio by
      a factor of 2.0 +/- 0.2 in the intact uterus. Salbutamol, the positive control,
      increased this activity ratio in both longitudinal myometrium (by 1.9 +/- 0.3
      times) and in the intact uterus (by 3.8 +/- 0.3 times), whereas the negative
      control levcromakalim had no effect. Relaxin seems to act as a relaxant of
      longitudinal myometrium by a cyclic AMP-independent mechanism but possibly
      interacts with the circular myometrium or endometrium to release a relaxant
      factor via a cyclic-AMP-dependent mechanism.

PMID- 9155742
TI  - Characteristics of koala (Phascolarctos cinereus adustus) semen collected by
      artificial vagina.
AB  - Collection of semen using a modified ovine artificial vagina was attempted on 90
      occasions from 25 Queensland koalas (Phascolarctos cinereus adustus). Complete
      ejaculates consisting of a copulatory plug and sperm fraction were collected on
      36 occasions (40%) from 19 animals. Seventeen of the males produced a complete
      ejaculate on their first or second service. Failure to collect semen (38%) and
      the collection of partial ejaculates (14.5%) was attributed to lack of sexual
      interest, aggressive behaviour towards the female by the male, the use of non
      compliant teaser females or a distinct dislike of the artificial vagina. Only a
      few ejaculates were contaminated with urine (4.5%) or obtained after ejaculation
      behaviour was terminated (3%). The mean (+/-SEM) values for the seminal
      characteristics of 19 complete ejaculates were: mass of copulatory plug fraction
      0.78 +/- 0.10 g, sperm fraction volume 0.73 +/- 0.10 ml, sperm concentration
      165.1 +/- 26.7 x 10(6) ml-1, pH of sperm fraction 6.7 +/- 0.2, osmolarity of
      sperm fraction 315.0 +/- 5.4 mOsm, percentage forward motility 70.7 +/- 1.8%,
      rate of sperm movement 4.0 +/- 0.1 and percentage of abnormal spermatozoa 26.9 +/
      2.5%. Percentages of sperm head morphotypes and tail abnormalities were
      documented. Although the artificial vagina technique is limited by the need for
      access to oestrous females, the procedure described has been shown to be a
      simple, reliable method of collecting semen from captive koalas.

PMID- 9155743
TI  - Fate and distribution of seminal plasma proteins in the genital tract of the
      female rat after natural mating.
AB  - This paper describes the distribution and fate of seminal plasma proteins in the
      rat female genital tract after insemination, using immunological detection in
      tissue sections and in fluids collected from different regions. The localization
      of seminal plasma proteins in the uterus and the vagina correlated with that of
      spermatozoa, suggesting that passive transport mechanisms operate in these
      regions. No seminal plasma proteins were detected in the oviduct, indicating that
      their presence is probably restricted to the uterine environment. Possible
      mechanisms for eliminating seminal plasma molecules after copulation include
      leakage from the uterus after relaxation of the cervical muscles and endocytosis
      by the endometrial cells. Large amounts of both vesicular and coagulating gland
      proteins were detected in the vagina of females at the time of cervical
      relaxation, indicating that the first mechanism of leakage from the uterus after
      cervical relaxation operates. Immunocytochemical procedures were used and seminal
      vesicle antigens were detected inside uterine epithelial cells, which indicates
      that endocytosis is also a mechanism for elimination of these molecules after
      copulation. Western blot results suggest proteolytic cleavage as a third
      mechanism. However, coagulating gland antigens are neither endocytosed nor
      cleaved, and their elimination takes place only by backflow to the vagina. The
      seminal plasma distribution in experimental situations in which sperm transport
      is altered was also studied. The implications of our findings for mechanisms of
      sperm transport in the female are discussed.

PMID- 9155744
TI  - Steroidogenic acute regulatory (StAR) protein (p25) and prohibitin (p28) from
      cultured rat ovarian granulosa cells.
AB  - This study has identified and characterized two intracellular proteins (25 and 28
      kDa) during ongoing differentiation of rat granulosa cells isolated from
      preantral and early antral follicles. The identity of p25 was confirmed as the
      mitochondria associated StAR protein by western blotting analysis. In the culture
      conditions used, this protein was expressed only when granulosa cells were
      stimulated with FSH to produce progesterone. It is apparent that the
      steroidogenic differentiation of granulosa cells affects StAR expression. Amino
      acid sequence analysis of p28 identified it as prohibitin and was corroborated by
      western blot analysis with antibodies specific for rat prohibitin. During the
      ongoing differentiation of granulosa cells there were changes in the expression
      of p28/prohibitin. Although prohibitin is constitutively expressed in granulosa
      cells, there is an increase in the more acidic isoform of prohibitin when
      oestrogen concentrations are raised by increased production or exogenous
      addition. This increase in this acidic isoform of prohibitin is due to
      phosphorylation. It is possible that oestrogen induces phosphorylation of
      prohibitin and, thus, may be involved in the regulation of granulosa cell
      proliferation and the ontogeny of the ovarian follicle.

PMID- 9155745
TI  - Expression of platelet-activating factor receptor in the hamster oviduct:
      localization to the endosalpinx.
AB  - Platelet-activating factor (PAF) is a lipid mediator that has a range of
      biological effects on various cells and tissues. PAF-like activity has been
      detected in the spent media of two-cell to morula stage hamster embryos, leading
      to the suggestion that PAF may be the embryonic signal that hastens embryo
      transport to the uterus in this species. The present study was undertaken to
      examine whether the PAF receptor (PAFr) gene is expressed in hamster oviduct, and
      to identify the cell types in which the gene is expressed. DNA fragments
      complementary to the coding region of mRNA encoding hamster PAFr were cloned by
      reverse transcription-polymerase chain reaction (RT-PCR), identified by
      sequencing and used to prepare hamster specific cRNA probes. The presence of mRNA
      transcripts encoding the PAFr receptor in the oviduct was investigated by
      subjecting oviduct mRNA to RT-PCR. Southern blot analysis of the RT-PCR products
      verified the identity of the presumptive PAFr cDNAs. The cloned cDNA fragment of
      hamster PAFr was found to be highly conserved with respect to the receptor of
      other species, having 94.3% sequence similarity to the rat PAFr receptor.
      Hybridization histochemistry demonstrated that PAFr is expressed in the
      subepithelial cells and occasionally in the epithelium. In conclusion, expression
      of PAFr in the hamster oviduct is compatible with the proposed paracrine role of
      early embryo-derived PAF.

PMID- 9155746
TI  - Bovine blastocyst production in vitro after inhibition of oocyte meiotic
      resumption for 24 h.
AB  - The aims of the present study were to assess the effect of various substances on
      meiotic resumption and subsequent development to the blastocyst stage of bovine
      oocytes. Immature cumulus-oocyte complexes were cultured for 24 h in (a) Medium
      199 (M199) alone, or M199 supplemented with (b) 10% fetal calf serum (FCS), (c) 1
      micrograms cycloheximide ml-1, (d) 2 mmol 6-dimethylaminopurine (6-DMAP) l-1, or
      (e) 0.1 mmol vanadate l-1. After 24 h, groups (a) and (b) were inseminated with
      frozen-thawed spermatozoa and subsequently cultured, while groups (c-e) were
      washed and cultured for a second 24 h in M199 + FCS, after which they were
      inseminated and cultured. At all time points a representative sample of oocytes
      were fixed and stained with orcein to observe the nuclear status, while others
      were labelled with [35S]methionine to study protein biosynthesis. Incubation with
      6-DMAP, cycloheximide or vanadate completely blocked germinal vesicle breakdown
      with most oocytes remaining at the germinal vesicle stage after 24 h culture
      (89%, 100% and 85%, respectively). This inhibitory effect was fully reversible in
      the case of 6-DMAP and cycloheximide; after a second period of incubation,
      germinal vesicle breakdown occurred in almost all cases (99% and 100%,
      respectively), and most reached metaphase II (85% and 83%, respectively). In
      contrast, inhibition with vanadate was only reversible in 56% of oocytes, with
      only 6% reaching metaphase II. Cleavage rates at 72 h after insemination and
      blastocyst yields on day 8 of culture were, respectively: (i) M199, 72% and 34%;
      (ii) M199 + FCS, 80% and 45%; (iii) M199 + cycloheximide, 81% and 19%; (iv) M199
      + 6-DMAP, 77% and 14%. 6-DMAP did not modify methionine incorporation. However,
      cycloheximide completely blocked protein synthesis when present during the period
      of labelling. Addition of epidermal growth factor to cycloheximide-inhibited
      oocytes was without effect. In contrast, epidermal growth factor overcame the
      effect of 6-DMAP in about 50% of oocytes, resulting in lower developmental rates
      after IVF. These results give an indication of the feasibility of in vitro
      meiotic inhibition as a tool in the study of the mechanisms involved in
      acquisition of competence.

PMID- 9155748
TI  - Acute renal failure in general surgery.
AB  - The high mortality and morbidity can be significantly reduced by three cardinal
      steps: 1. Early diagnosis of intrinsic renal failure 2. Early institution of
      fluid restriction and dialysis 3. The identification of patients who are likely
      to be at high risk from acute renal failure, and the careful planning and
      institution of available therapeutic measures to prevent it.

PMID- 9155749
TI  - Hospital-at-home: buyer beware.

PMID- 9155750
TI  - The defeat of deafness.

PMID- 9155747
TI  - A tribute to professor Geoffrey D Chisholm CBE ChM PPRCS Ed FRCS Eng FRCP Ed
      FRCPSG FRACS (Hon) FCSSA (Hon) FACS (Hon) FRSE.

PMID- 9155751
TI  - Measuring hospital performance: are we asking the right questions?

PMID- 9155752
TI  - Cytotoxic endocrinopathy: a legacy of insults.

PMID- 9155753
TI  - Leukotriene receptor antagonists: clinical effects.

PMID- 9155754
TI  - Conversation analysis: a new model of research in doctor-patient communication.

PMID- 9155755
TI  - Chronic coronary occlusions: age, morphology and chance of reopening.
AB  - In chronic coronary occlusions the chance of successful reopening by angioplasty
      can be judged from the age of the occlusion. Often, however, time since occlusion
      cannot be accurately assessed. Therefore we determined whether the chance of
      reopening can be predicted from angiographic morphology. In cineangiograms from
      60 consecutive patients with chronic coronary occlusions morphological details in
      at least two projections were evaluated in relation to the rate of success and
      the estimated age of occlusion. Morphological features associated with a higher
      rate of success (type A) were a clearcut proximal stump, absence of side branches
      at the site of occlusion, absence of bridging collaterals, and only slight
      filling of the distal part of the vessel. Features associated with a low success
      rate (type B) were absence of proximal stump, side branches at the site of
      occlusion, bridging collaterals, and rapid high-contrast filling of the distal
      part of the vessel. 48/60 (80%) of occlusions could be classified as type A or
      type B. The success rate was 17/21 (81%) in type A versus 5/27 (18.5%) in type B
      (P < 0.0002). The estimated age of type B occlusions was higher than that of type
      A medians 8 and 4 months (P < 0.002). Thus in chronic coronary occlusions the
      likelihood of successful reopening can be judged in many patients from
      morphological features.

PMID- 9155756
TI  - Does the National Health Service want hospital-at-home?
AB  - There has been increasing interest in the development of hospital-at-home within
      the National Health Service (NHS) as a way of shifting resources from secondary
      to primary care. We describe the development of hospital-at-home schemes in
      London and draw on data from an evaluation of five such schemes to discuss
      support for hospital-at-home within the NHS. The study has identified a small but
      important group of patients who do not want hospital-at-home, as well as
      resistance to it from some health care professionals and managers, particularly
      in hospitals. These organizational issues must be taken into account in any
      evaluation of hospital-at-home, along with issues of quality, outcome and cost.
      Feasibility studies are needed to identify possible organizational barriers to
      hospital-at-home and the development work that is required. This service
      innovation should not be considered in isolation from other services, but rather
      within the context of a wider debate about the pattern of acute care.

PMID- 9155757
TI  - Carpal tunnel syndrome as a herald of autoimmune rheumatic disorders.
AB  - In six patients aged 59-71 years carpal tunnel syndrome, seemingly idiopathic,
      was followed by connective tissue disorders, in most cases autoimmune in nature.
      Patients with idiopathic carpal tunnel syndrome may therefore require long-term
      follow-up, if inflammatory rheumatic conditions are not to be missed.

PMID- 9155758
TI  - A survey of croquet injuries.
AB  - Of 214 croquet players who responded to a questionnaire, 76 reported at least one
      injury to hand, wrist or forearm caused by striking the ball. There was no
      obvious relation to which of the three main grips the player applied to the
      mallet. Injuries were somewhat more frequent when the mallet shaft consisted of
      fibreglass than when it was wood, metal or carbon fibre, but a causal relation
      has not been established. Back injuries seem less troublesome in croquet than in
      golf.

PMID- 9155759
TI  - Abdominal pain of psychotic origin.

PMID- 9155760
TI  - Pregnancy assisted by nasal intermittent positive pressure ventilation in a
      patient with cystic fibrosis.

PMID- 9155761
TI  - A 'destructive' headache.

PMID- 9155762
TI  - The ideas of Thomas Kuhn in relation to medical advances in the sixteenth and
      seventeenth centuries.

PMID- 9155763
TI  - The Hammersmith.

PMID- 9155764
TI  - Coronary heart disease in Africa.

PMID- 9155765
TI  - Coronary heart disease in Africa.

PMID- 9155766
TI  - Euthanasia.

PMID- 9155767
TI  - Haemoglobin and ESR.

PMID- 9155768
TI  - Haemoglobin and ESR.

PMID- 9155769
TI  - Private psychiatry and the NHS.

PMID- 9155770
TI  - Sailors, scurvy, science and authority.

PMID- 9155771
TI  - Stress and cancer.

PMID- 9155772
TI  - Electronic journals.

PMID- 9155773
TI  - Complementary medicine in the medical curriculum.

PMID- 9155774
TI  - Randomized trial of homeopathic arnica.

PMID- 9155775
TI  - Methods for assessing the extent of exposure and effects of air pollution.
AB  - BACKGROUND AND OBJECTIVES: In many places in Europe, the ambient air pollution
      exceeds the levels considered to be safe for health. The objective of the paper
      is to review and summarise the methods of assessment of its impact on health, and
      to indicate the contributions of various research disciplines, particularly
      environmental epidemiology. METHODS: The framework for assessment of impact is
      based on a four stage model: assessment of release of pollutant; assessment of
      exposure; assessment of the consequence; and risk estimation. RESULTS:
      Epidemiology is crucial in providing the data for the assessment of consequence.
      The criteria that determine the use of epidemiological studies for this task
      include lack of bias, correct control of confounding, and measured estimates of
      exposure. At present, those criteria are easier to satisfy for studies of short
      term effects on health than for the delayed consequences of exposure, or exposure
      accumulated over a prolonged period. Combinations of results from various
      populations through meta-analysis of existing studies or conducting multicentre
      studies is often necessary to increase the reliability of the consequence
      assessment stage. CONCLUSION: To assess the impact on health systematically helps
      to focus on actions to limit air pollutants with the greatest impacts on human
      health and on the most affected populations. This method allows identification of
      the most pertinent questions which have to be answered by studies on relations
      between pollution and health and on exposure of populations to air pollutants.
      Epidemiology has considerable potential to contribute to this research.

PMID- 9155777
TI  - Retrospective estimation of exposure to benzene in a leukaemia case-control study
      of petroleum marketing and distribution workers in the United Kingdom.
AB  - OBJECTIVE: To provide quantitative estimates of exposure to benzene for cases and
      controls in an epidemiology study to investigate the risk of leukaemia in
      petroleum distribution workers. METHODS: Work histories were obtained for cases
      and controls together with detailed information on the distribution sites. For
      each job in the work history, an estimate of exposure (parts per million (ppm))
      was obtained by multiplying a measure derived from exposure data by modifying
      factors to reflect the differences between the conditions that existed at the
      time of measurement and those at the time of interest. The modifying factors used
      related to job activity, the number of road tankers loaded, the benzene content
      of the gasoline, the mixture of products handled, temperature, and loading
      technology. Cumulative exposures for each case and control were obtained by
      multiplying the exposure estimates for each job by the duration of time in the
      respective jobs, and summing these over all jobs in the work history. Peak
      exposure and exposure through dermal contact were quantitatively classified for
      each job. RESULTS: Measured exposures were obtained for 30 job categories, and
      ranged from 0.003 to 8.20 ppm. 40% of work histories were assigned background
      exposures, with a further 34% assigned the exposure estimate for a driver
      carrying out top submerged loading of motor fuel into road tankers. Cumulative
      exposures ranged from < 1 to > 200 ppm-years, although 81% were < 5 ppm-years.
      Comparison of the exposure estimates for selected jobs with data from sources not
      used in the study showed similar results. CONCLUSION: The estimates of exposure
      to benzene in this study provide a sound basis for the epidemiological analyses.

PMID- 9155776
TI  - A case-control study to investigate the risk of leukaemia associated with
      exposure to benzene in petroleum marketing and distribution workers in the United
      Kingdom.
AB  - OBJECTIVES: To investigate the risk of leukaemia in workers in the petroleum
      distribution industry who were exposed to low levels of benzene. METHODS: From
      the cohort of distribution workers, 91 cases were identified as having leukaemia
      on either a death certificate or on cancer registration. These cases were
      compared with controls (four per case) randomly selected from the cohort, who
      were from the same company as the respective case, matched for age, and alive and
      under follow up at the time of case occurrence. Work histories were collected for
      the cases and controls, together with information about the terminals at which
      they had worked, fuel compositions, and occupational hygiene measurements of
      benzene. These data were used to derive quantitative estimates of personal
      exposure to benzene. Odds ratios (OR) were calculated conditional on the
      matching, to identify those variables in the study which were associated with
      risk of leukaemia. Examination of the potential effects of confounding and other
      variables was carried out with conditional logistic regression. Analyses were
      carried out for all leukaemia and separately for acute lymphoblastic, chronic
      lymphocytic, acute myeloid and monocytic, and chronic myeloid leukaemias.
      RESULTS: There was no significant increase in the overall risk of all leukaemias
      with higher cumulative exposure to benzene or with intensity of exposure, but
      risk was consistently doubled in subjects employed in the industry for > 10
      years. Acute lymphoblastic leukaemia tended to occur in workers employed after
      1950, who started work after the age of 30, worked for a short duration, and
      experienced low cumulative exposure with few peaks. The ORs did not increase with
      increasing cumulative exposure. The risk of chronic lymphocytic leukaemia seemed
      to be related most closely to duration of employment and the highest risk
      occurred in white collar workers with long service. These workers had only
      background levels of benzene exposure. There was no evidence of an association of
      risk with any exposure variables, and no evidence of an increasing risk with
      increasing cumulative exposure, mean intensity, or maximum intensity of exposure.
      The patterns of risk for acute myeloid and monocytic leukaemia were different
      from those of the lymphoid subgroups, in which duration of employment was the
      variable most closely related to risk. Risk was increased to an OR of 2.8 (95%
      confidence interval (95% CI) 0.8 to 9.4) for a cumulative exposure between 4.5
      and 45 ppm-years compared with < 0.45 ppm-years. For mean intensity between 0.2
      and 0.4 ppm an OR of 2.8 (95% CI 0.9 to 8.5) was found compared with < 0.02 ppm.
      Risk did not increase with cumulative exposure, maximum intensity, or mean
      intensity of exposure when treated as continuous variables. Cases of acute
      myeloid and monocytic leukaemia were more often classified as having peaked
      exposures than controls, and when variables characterising peaks, particularly
      daily and weekly peaks, were included in the analysis these tended to dominate
      the other exposure variables. However, because of the small numbers it is not
      possible to distinguish the relative influence of peaked and unpeaked exposures
      on risk of acute myeloid and monocytic leukaemia. There was no evidence of an
      increased risk of chronic myeloid leukaemia with increases in cumulative
      exposure, maximum intensity, mean intensity, and duration of employment, either
      as continuous or categorical variables. Analyses exploring the sensitivity of the
      results to the source and quality of the work histories showed similar patterns
      in general. However, no increases in ORs for categories of cumulative exposure
      were found for acute myeloid and monocytic leukaemia in the data set which
      included work histories obtained from personnel records still in existence,
      although numbers were reduced. Analyses excluding the last five and 10 years of
      exposure showed a tendency for ORs to reduce for chronic lymphocytic leukaemia
      and chronic myeloid leukaemia, and to increase for acute myeloid and monocytic
      leukaemia. Limitations of the study include uncertainties and gaps in the
      information collected, and small numbers in subcategories of exposure which can
      lead to wide CIs around the risk estimates and poor fit of the mathematical
      models. CONCLUSIONS: There is no evidence in this study of an association between
      exposure to benzene and lymphoid leukaemia, either acute or chronic. There is
      some suggestion of a relation between exposure to benzene and myeloid leukaemia,
      in particular for acute myeloid and monocytic leukaemia. Peaked exposures seemed
      to be experienced for this disease. However, in view of the limitations of the
      study, doubt remains as to whether the risk of acute myeloid and monocytic
      leukaemia is increased by cumulative exposures of < 45 ppm-years. Further work is
      recommended to review the work histories and redefine their quality, to explore
      the discrepancies between results for categorical and continuous variables, and
      to develop ranges around the expose estimates to enable further sensitivity
      analyses to be carried out.

PMID- 9155778
TI  - DNA single strand breakage, DNA adducts, and sister chromatid exchange in
      lymphocytes and phenanthrene and pyrene metabolites in urine of coke oven
      workers.
AB  - OBJECTIVES: To investigate the specificity of biological monitoring variables
      (excretion of phenanthrene and pyrene metabolites in urine) and the usefulness of
      some biomarkers of effect (alkaline filter elution, 32P postlabelling assay,
      measurement of sister chromatid exchange) in workers exposed to polycyclic
      aromatic hydrocarbons (PAHs). METHODS: 29 coke oven workers and a standardised
      control group were investigated for frequencies of DNA single strand breakage,
      DNA protein cross links (alkaline filter elution assay), sister chromatid
      exchange, and DNA adducts (32P postlabelling assay) in lymphocytes. Phenanthrene
      and pyrene metabolites were measured in 24 hour urine samples. 19 different PAHs
      (including benzo(a)pyrene, pyrene, and phenanthrene) were measured at the
      workplace by personal air monitoring. The GSTT1 activity in erythrocytes and
      lymphocyte subpopulations in blood was also measured. RESULTS: Concentrations of
      phenanthrene, pyrene, and benzo(a)pyrene in air correlated well with the
      concentration of total PAHs in air; they could be used for comparisons of
      different workplaces if the emission compositions were known. The measurement of
      phenanthrene metabolites in urine proved to be a better biological monitoring
      variable than the measurement of 1-hydroxypyrene. Significantly more DNA strand
      breaks in lymphocytes of coke oven workers were found (alkaline filter elution
      assay); the DNA adduct rate was not significantly increased in workers, but
      correlated with exposure to PAHs in a semiquantitative manner. The number of
      sister chromatid exchanges was lower in coke oven workers but this was not
      significant; thus counting sister chromatid exchanges was not a good variable for
      biomonitoring of coke oven workers. Also, indications for immunotoxic influences
      (changes in lymphocyte subpopulations) were found. CONCLUSIONS: The measurement
      of phenanthrene metabolites in urine seems to be a better biological monitoring
      variable for exposure to PAHs than measurement of hydroxypyrene. The alkaline
      filter elution assay proved to be the most sensitive biomarker for genotoxic
      damage, whereas the postlabelling assay was the only one with some specificity
      for DNA alterations caused by known compounds.

PMID- 9155779
TI  - Risk of lung cancer among masons in Iceland.
AB  - OBJECTIVES: To estimate the risk of gastrointestinal cancer and lung cancer in a
      cohort of masons exposed to cement and hexavalent chromium by a follow up in the
      Icelandic Cancer Registry. METHODS: The cohort, 1172 men, was defined as those
      who had served their apprenticeship and were fully licensed as masons (cement
      finishers) in Iceland, were born after 1880 and were alive in 1955. The men were
      exposed to an aerosol of wet concrete, particularly when spraying. According to
      the analyses of urinary chromium the masons were exposed to hexavalent chromium.
      A computer file on masons was record linked to the Cancer Registry by making use
      of the personal identification numbers. Expected cancer incidence was calculated
      on the basis of number of person-years for each five-year age category during the
      individual calendar years of the study period and multiplied by the specific
      incidence for cause and calendar year for men in Iceland provided by the Cancer
      Registry. RESULTS: The standardised incidence ratio (SIR) for all cancers was
      1.13 in the total cohort and 1.33 when allowance was made for 30 years to elapse
      before starting to count person years of risk. The risk for gastrointestinal
      cancers was not increased. The SIR for lung cancer was 1.69 in the total cohort
      and 1.77 when a lag of 30 years was included. The SIR for lung cancer among those
      born in 1920 or later was 1.86. Results from a postal questionnaire showed that
      fewer masons had never smoked and more masons had stopped smoking than the
      controls from the general population. CONCLUSION: The increased risk of lung
      cancer among the masons may be related to their work. The exposure information,
      although limited, supports the suggestion that hexavalent chromium in the cement
      may be the causal link, as information on the smoking habits indicate that the
      control for this important possible confounder is adequate.

PMID- 9155781
TI  - Lung cancer mortality in a cohort of workers employed at a cadmium recovery plant
      in the United States: an analysis with detailed job histories.
AB  - OBJECTIVES: To identify and measure any relations between occupational exposure
      to cadmium compounds (oxide, sulphide, and sulphate) and the risk of mortality
      from lung cancer. METHODS: The mortality experience of 571 male production
      workers from a cadmium recovery facility in the United States was investigated
      for the period 1940-82. All study subjects were first employed in the period 1926
      69; they had all been employed for at least six months between 1 January 1940 and
      31 December 1969. Newly abstracted detailed job histories for the period 1926-76
      were combined with assessments of exposures to cadmium over time to develop
      individual estimates of cumulative exposure to cadmium (total exposure and
      exposures received both in the presence and absence of "high" exposures to
      arsenic trioxide). Poisson regression was used to investigate risks of mortality
      from lung cancer in relation to four concentrations of cumulative exposure to
      cadmium (< 400, 400-999, 1000-1999, > 2000 mg.m-3.days). RESULTS: After
      adjustment for age attained, year of hire, and Hispanic ethnicity, there was a
      significant positive trend (P < 0.05) between cumulative exposure to cadmium and
      risks of mortality from lung cancer. Relative to a risk of unity for the lowest
      exposure category (first level), risks were 2.30 (95% confidence interval (95%
      CI) 0.72 to 7.36), 2.83 (95% CI 0.75 to 10.72), and 3.88 (95% CI 1.04 to 14.46)
      for the second, third, and fourth categories, respectively. Similar findings were
      obtained after adjustment for age only. Trends were more pronounced when
      employment histories were lagged first by 10 years and then by 20 years. A
      separate analysis examined the independent effects of exposure to cadmium
      received in the presence of high exposures to arsenic trioxide (mainly cadmium
      oxide) and exposures to cadmium received without such exposure to arsenic (mainly
      cadmium sulphide and cadmium sulphate). A significant trend for a risk of lung
      cancer was found only for exposures to cadmium received in the presence of
      arsenic trioxide. CONCLUSIONS: Hypotheses which are consistent with the study
      findings include: (a) cadmium oxide in the presence of arsenic trioxide is a
      human lung carcinogen, (b) cadmium oxide and arsenic trioxide are human lung
      carcinogens and cadmium sulphate and cadmium sulphide are not (or they are less
      potent carcinogens), or (c) arsenic trioxide is a human lung carcinogen and
      cadmium oxide, cadmium sulphate, and cadmium sulphide are not. There were only 21
      deaths from lung cancer available for this analysis and it is impossible to gauge
      which, if any, of these hypotheses are correct.

PMID- 9155780
TI  - Increased risk of lung cancer among male professional drivers in urban but not
      rural areas of Sweden.
AB  - OBJECTIVES: To study the risk of lung cancer in different subgroups of
      professional drivers in urban and rural areas of Sweden. METHODS: Information on
      occupation and geographical region was obtained from the Swedish census of 1970
      and data on the incidence of lung cancer between 1971 and 1984 from the National
      Swedish Cancer Registry. Professional drivers were separated into bus, taxi, and
      long and short distance lorry drivers. Comparisons of cumulative incidence of
      lung cancer were made between each particular group of drivers and gainfully
      employed men in the same region. RESULTS: Taxi drivers, and long and short
      distance lorry drivers in Stockholm County showed increased relative risks (RRs)
      of lung cancer with the highest risk among the short distance lorry drivers (RR
      2.0, 95% confidence interval (95% CI) 1.5 to 2.6). These categories of drivers
      also showed increased risks in the other two large conurbations in Sweden. In the
      rest of the country (mainly rural areas) there were no increased RRs for any
      category of driver. The RR for bus drivers was not increased in any region. After
      adjustment for assumed differences in smoking habits the RRs remained
      significantly increased for lorry drivers in Stockholm but not for other groups
      of drivers in other areas. However, the RRs remained numerically higher in large
      conurbations than in rural regions for all groups of drivers. CONCLUSIONS: These
      findings suggest that some factors present in the urban environment play a
      substantial part in the excess of lung cancer among short distance lorry drivers
      in urban areas of Sweden. Exposure to motor exhaust fumes may have contributed to
      this excess.

PMID- 9155782
TI  - Occupational exposure to ionising radiation and mortality among workers of the
      former Spanish Nuclear Energy Board.
AB  - OBJECTIVES: Firstly, to ascertain whether mortality among workers of the former
      Spanish Nuclear Energy Board (Junta de Energia Nuclear-JEN) was higher than that
      for the Spanish population overall; and secondly, if this were so, to ascertain
      whether this difference was associated with exposure to ionising radiation.
      METHODS: A retrospective follow up of a cohort of 5657 workers was carried out
      for the period 1954-92. Cohort mortality was compared with that for the Spanish
      population overall, with standardised mortality ratios (SMRs) adjusted for sex,
      age, and calendar period. Also, Poisson models were used to analyse mortality
      from lung cancer in the cohort by level of exposure to ionising radiation.
      RESULTS: Workers' median and mean cumulative exposures were 4.04 and 11.42 mSv,
      respectively. Mean annual exposure was 1.33 mSv. Excess mortality due to bone
      tumours was found for the cohort as a whole (six deaths observed; SMR 2.95; 95%
      confidence interval (95% CI) 1.08 to 6.43). Among miners, excess mortality was
      found for non-malignant respiratory diseases (SMR 2.94; 95% CI 2.27 to 3.75), and
      for lung cancer bordering on statistical significance (SMR 1.50; 95% CI 0.96 to
      2.23; P = 0.055). Relative risks of dying of lung cancer from ionising radiation
      in the dose quartiles 2, 3, and 4 versus the lowest dose quartile, were 1.00,
      1.64, and 0.94, respectively. CONCLUSIONS: Excess mortality from lung cancer was
      found among JEN miners. Nevertheless, no clear relation was found between
      mortality from lung cancer and level of exposure to ionising radiation in the JEN
      cohort. Continued follow up of the cohort is required to confirm excess mortality
      from bone tumours.

PMID- 9155784
TI  - Cancer mortality among workers in the German rubber industry.

PMID- 9155783
TI  - The mortality of Royal Naval submariners 1960-89.
AB  - OBJECTIVES: To examine the mortality pattern of submariners in the Royal Navy to
      assess the long term effects on health of serving in submarines. Any specific
      cause of death which was increased was considered in advance to be of interest,
      but attention focused particularly on cancer mortality. METHOD: A mortality
      follow up study: 15 138 submariners who had conducted their first submarine
      training between 1960 and 1979 were followed up through their time in the Navy
      and into civilian life, up to the end of 1989. The main outcome measures were the
      numbers of deaths and standardised mortality ratios (SMRs) which indicate whether
      the mortality from all causes and specific causes, particularly cancers, exceeds
      that in men in England and Wales. RESULTS: Mortality in submariners was lower
      than that for men in England and Wales with an all cause SMR of 86; this was
      comparable with that found in other studies of armed forces personnel. Cancer
      mortality was particularly low with an SMR of 69 and there was no particular
      cancer site which showed an excess. Increased mortality from digestive diseases
      was found, the excess being attributable to cirrhosis of the liver, which had an
      SMR of 221 based on 12 deaths, alcohol being a contributory factor in eight.
      Deaths from accidents and violence were also higher than expected with an SMR of
      115, but this was due to high levels of accidents occurring after discharge from
      the Navy. There was no apparent trend in mortality with time since starting
      submarine work. Likewise there was no pattern by calendar period, although the
      excess of cirrhosis of the liver was confined to the period 1970-9. CONCLUSION:
      The submariners seemed to be a healthy group with low mortality overall. Working
      in submarines was not associated with any increased cancer mortality. Excess
      deaths from cirrhosis of the liver, and from accidents and violence after leaving
      the Navy, were of some concern but they cannot be attributed directly to the
      submarine environment.

PMID- 9155785
TI  - Careful with the zeros! How to minimize one of the most persistent causes of
      gross medication errors.

PMID- 9155786
TI  - Misguided mercy.

PMID- 9155787
TI  - No endorsement implied.

PMID- 9155788
TI  - When does 'drug-seeking' behavior signal addiction?

PMID- 9155789
TI  - Medicare legislation: reimbursement, patient protection addressed.

PMID- 9155791
TI  - Guarding against adverse drug events.

PMID- 9155790
TI  - Was this consent informed?

PMID- 9155792
TI  - Emergency! Hypertensive crisis from drug-food interaction.

PMID- 9155793
TI  - Back to Basics: providing effective patient teaching.

PMID- 9155794
TI  - More than a friend: the special bond between nurses.

PMID- 9155795
TI  - Clinical snapshot: mitral valve prolapse.

PMID- 9155797
TI  - Pants not required. This nurse will never forget her first hospice assignment.

PMID- 9155796
TI  - Cancer-related hypercalcemia: how to spot it, how to manage it.

PMID- 9155798
TI  - Combating dangerous delegation.

PMID- 9155799
TI  - Common questions about ductal carcinoma in situ.

PMID- 9155800
TI  - Wellness for nurses, by nurses. Extended Services Team at the Visiting Nurse
      Association of Northern Virginia.

PMID- 9155801
TI  - Working toward recovery with the lesbian patient.

PMID- 9155803
TI  - Facial photography for the orthodontic office.

PMID- 9155802
TI  - Violence prevention begins at home--with nurses.

PMID- 9155804
TI  - A case of hyperodontia with twenty-two supernumeraries: its surgical-orthodontic
      treatment.
AB  - A 10.1-year-old boy showed no permanent teeth, with the exception of the lower
      central incisors. An x-ray examination revealed that eruption of the permanent
      dentition was obstructed by 1 deciduous supernumerary and 22 permanent
      supernumeraries ectopically. Treatment consisted of the following steps: (1)
      extracting all deciduous and supernumerary teeth; (2) waiting for the roots of
      the permanent teeth to develop and fitting two temporary partial prostheses; (3)
      assisting eruption of the permanent teeth by removing the bone that covers the
      remaining teeth and applying crowns to stimulate the eruption; and (4) bringing
      the permanent teeth into occlusion with orthodontic treatment. The problem of
      limiting treatment time was made more difficult by the amount of repositioning
      needed to bring the teeth into occlusion and by delayed root formation. Therefore
      the orthodontist decided to use extreme caution in applying forces; as a result,
      treatment time was lengthened. Success was due to good teamwork between the
      surgeon with an orthodontic background and the orthodontist, who was familiar
      with surgical procedures.

PMID- 9155806
TI  - An American Board of Orthodontics case report.

PMID- 9155805
TI  - Two-stage treatment of a severe skeletal Class III, deep bite malocclusion.

PMID- 9155807
TI  - Effect of electric toothbrushes versus manual toothbrushes on removal of plaque
      and periodontal status during orthodontic treatment.
AB  - This study compared the effectiveness of three different types of electric
      toothbrushes, i.e., Interplak, Philips, and Rotadent, with a manual multitufted
      toothbrush (Blend-a-Med), in removing supragingival plaque and in preventing the
      development of gingivitis in adolescent patients with fixed orthodontic
      appliances. A single blind, cross-over, clinical trial was carried out in 36
      adolescent patients, randomly divided into four equal groups. Every group tested
      each type of toothbrush, in a different sequence. Plaque and gingival scores were
      recorded at baseline and after 1 and 2 months of the test period. All patients
      received a professional prophylaxis after each clinical evaluation, except during
      the test period. The analysis of the data was performed with the nonparametric
      Friedman test. The results demonstrated, in essence, for all parameters that the
      manual toothbrush was the most effective. Of the three electric toothbrushes
      tested, the Philips toothbrush seemed to give slightly better results than the
      Interplak toothbrush, whereas Rotadent very clearly gave results inferior to all
      others. Personal preference on the four toothbrushes used revealed that the group
      as a whole least preferred a manual brush. However, the answers on the
      questionnaire did not always show a logical consistency. Therefore it should be
      interpreted with some caution.

PMID- 9155808
TI  - Evaluation of Scotchbond Multipurpose and maleic acid as alternative methods of
      bonding orthodontic brackets.
AB  - Damage to the enamel surface during bonding and debonding of orthodontic brackets
      is a clinical concern. Alternative bonding methods that minimize enamel surface
      damage while maintaining a clinically useful bond strength is an aim of current
      research. The purpose of this study was to compare the effects on bond strength
      and bracket failure location of two adhesives (System 1+ and Scotchbond
      Multipurpose, 3M Dental Products Division) and two enamel conditioners (37%
      phosphoric acid and 10% maleic acid). Forty-eight freshly extracted human
      premolars were pumiced and divided into four groups of 12 teeth, and metal
      orthodontic brackets were attached to the enamel surface by one of four
      protocols: (1) System 1+ and phosphoric acid, (2) Scotchbond and phosphoric acid,
      (3) System 1+ and maleic acid, and (4) Scotchbond and maleic acid. After bracket
      attachment, the teeth were mounted in phenolic rings and stored in deionized
      water at 37 degrees C for 72 hours. A Zwick universal testing machine (Zwick GmbH
      & Co.) was used to determine shear bond strengths. The residual adhesive on the
      enamel surface was evaluated with the Adhesive Remnant Index. The analysis of
      variance was used to compare the four groups. Significance was predetermined at p
      < or = 0.05. The results indicated that there were no significant differences in
      bond strength among the four groups (p = 0.386). The results of the Chi square
      test, evaluating the residual adhesives on the enamel surfaces, revealed
      significant differences among the four groups (mean 2 = 0.005). A Duncan multiple
      range test revealed the difference occurred between the phosphoric acid and
      maleic acid groups, with maleic acid having bond failures at the enamel-adhesive
      interface. In conclusion, the use of Scotchbond Multipurpose and/or maleic acid
      does not significantly effect bond strength, however, the use of maleic acid
      resulted in an unfavorable bond failure location.

PMID- 9155811
TI  - Dynamic relationships of the mandibular anterior segment.
AB  - The hyperbolic cosine function is shown to be an accurate representation of the
      form of the mandibular anterior teeth from the canine/first premolar contact on
      one side around the perimeter to the opposite side (r = 0.951). On the basis of
      this mathematical function, the changes in canine width, anterior segment depth,
      arch perimeter, and their related incisor angular alterations are forecastable.
      This knowledge will allow the clinician to predict the effects on various aspects
      of the anterior segment arch form as one or more of these variables are altered
      without resorting to trial and error or performing a wax-up. For example, the
      clinician can predict the change in the anterior segment arch depth and incisor
      angulation that would occur with alterations in canine width.

PMID- 9155810
TI  - Individualized evaluation of facial form.
AB  - The purpose of this study was to establish a nonnumeric graphic approach to the
      evaluation of facial form. By using a centroid-based pattern of orientation,
      skeletal, dental, and soft-tissue morphologic characteristics can be identified
      that more reliably represent the uniqueness of the person and are not dependent
      on nonrepresentative group-based numerical standards. The CentroGraphic Analysis
      (CGA) cephalomorphically demonstrates vertical and horizontal balance or
      disharmony in skeletal, dental, and soft-tissue form and position. The Facial
      Centroid Axis (FCA) provides a relatively stable reference plane that can be used
      for longitudinal cephalomorphic superimposition.

PMID- 9155809
TI  - Early dentofacial features of Class II malocclusion: a longitudinal study from
      the deciduous through the mixed dentition.
AB  - A group of 25 untreated subjects with Class II malocclusion in the deciduous
      dentition (featuring the concomitant presence of distal step, Class II deciduous
      canine relationship, and excessive overjet) was compared with a control group of
      22 untreated subjects with ideal occlusion (flush terminal plane, Class I
      deciduous canine relationship, minimal overbite, and overjet) at the same
      dentitional stage. The subjects were monitored during a 2 1/2-year period in the
      transition from the deciduous to the mixed dentition, during which time no
      orthodontic treatment was provided. Occlusal analysis of the Class II group in
      the deciduous dentition revealed an average interarch transverse discrepancy due
      to a narrow maxillary arch relative to the mandible. All occlusal Class II
      features were maintained or became exaggerated during the transition to the mixed
      dentition. The skeletal pattern of Class II malocclusion in the deciduous
      dentition typically was characterized by significant mandibular skeletal
      retrusion and mandibular size deficiency. During the period examined,
      cephalometric changes consisted of significantly greater maxillary growth
      increments and smaller increments in mandibular dimensions in the Class II
      sample. Moreover, a greater downward and backward inclination of the condylar
      axis relative to the mandibular line, with consequent smaller decrements in the
      gonial angle, were found in the Class II group, an indication of posterior
      morphogenetic rotation of the mandible in patients with Class II malocclusion
      occurring during the period examined. The results of this study indicate that the
      clinical signs of Class II malocclusion are evident in the deciduous dentition
      and persist into the mixed dentition. Whereas treatment to correct the Class II
      problem can be initiated in all three planes of space (e.g., RME, extraoral
      traction, functional jaw orthopedics), other factors such as patient cooperation
      and management must also be taken into consideration before early treatment is
      started.

PMID- 9155812
TI  - Stimulatory effects of low-power laser irradiation on bone regeneration in
      midpalatal suture during expansion in the rat.
AB  - The purpose of this study was to investigate the effects of low-power laser
      irradiation on bone regeneration during expansion of a midpalatal suture in rats.
      Gallium-aluminum-arsenide diode laser 100 mW irradiation was applied to the
      midpalatal suture during expansion carried out over 7 days (3 or 10 minutes per
      day), 3 days (7 minutes per day for day 0-2 or 4-6), and 1 day (21 uninterrupted
      minutes on day 0). The bone regeneration in the midpalatal suture estimated by
      histomorphometric method in the 7-day irradiation group showed significant
      acceleration at 1.2- to 1.4-fold compared with that in the nonirradiated rats,
      and this increased rate was irradiation dose-dependent. Irradiation during the
      early period of expansion (days 0 to 2) was most effective, whereas neither the
      later period (days 4 to 6) nor the one-time irradiation had any effect on bone
      regeneration. These findings suggest that low-power laser irradiation can
      accelerate bone regeneration in a midpalatal suture during rapid palatal
      expansion and that this effect is dependent not only on the total laser
      irradiation dosage but also on the timing and frequency of irradiation. We
      suggest laser therapy may be of therapeutic benefit in inhibiting relapse and
      shortening the retention period through acceleration of bone regeneration in the
      midpalatal suture.

PMID- 9155814
TI  - Relapse revisited.
AB  - Rather little is known about the changes in orthodontic treatment results
      exceeding a decade after treatment. The purpose of this study was to quantify
      changes in tooth relationships in a series of cases (n = 36) at 6 years and again
      at 15 years after treatment. The rate of change decreased with time, supporting
      the contention that most "relapse" occurs soon after treatment; continued change
      generally cannot be distinguished from normal aging processes that occur,
      regardless of whether a person had been treated orthodontically. There were
      minor, but statistically significant, associations between increased incisor
      irregularity ("relapse") and parasagittal growth of the jaws. Greater
      irregularity occurred when mandibular growth exceeded that of the maxilla,
      decreasing overjet and crowding the lower incisors within the containing arch of
      the maxilla. Overall, relapse tended to be less in these cases treated by a
      single experienced specialist that in university-based samples treated by
      multiple, orthodontic residents.

PMID- 9155813
TI  - Influences on the outcome of early treatment for Class II malocclusion.
AB  - In the first phase of a randomized clinical trial of early versus late Class II
      treatment, statistically significant differences were observed between the
      treatment and observation groups. However, there were wide variations in
      response. The change in jaw relationship (categorized as the annualized reduction
      in ANB angle) was favorable or highly favorable in 76% of the headgear, 83% of
      the functional appliance, and 31% of control (observation only) groups. The
      patient's initial skeletal severity, age/maturity at the outset of treatment,
      growth pattern, and cooperation with treatment were examined as possible
      influences on early growth modification treatment. Correlations between the
      annualized change in the ANB angle and any of the possible influences were close
      to zero and not statistically significant. We conclude that there is little to be
      gained from precisely timing early treatment to specific age/maturity markers and
      that a favorable reduction in Class II skeletal problems can occur for patients
      in a broad range of skeletal severity and growth patterns. Cooperation, measured
      as the number of hours of reported wear, or the clinical assessment of
      compliance, explained little of the variation in treatment response. The wide
      variation in growth seen in the untreated patients highlights the importance of
      well-controlled studies if clinicians are to improve their ability to select
      children with the greatest chances of a favorable treatment response.

PMID- 9155817
TI  - Emerging paradigms in orthodontics--an essay.

PMID- 9155815
TI  - Effects of orthodontic treatment on nutrient intake.
AB  - Orthodontists often advise their patients to eat soft foods after treatment to
      avoid pressure sensitivity. Yet there is little research as to how this affects
      nutrient intake. This study compared nutrient intake before and after orthodontic
      adjustment to see whether any changes occurred. Ten patients between the ages of
      12 and 16 years were selected from the University of Buffalo School of
      Orthodontics. These patients recorded the foods they ate for 3 days before and 3
      days after treatment. Treatment types studied were those that cause a significant
      level of pressure sensitivity such as an arch wire change. The recorded diets
      were analyzed with a paired two sample t test, with alpha = 0.05 as the
      significance level. The results of this study show a decrease in intake of copper
      and manganese after orthodontic adjustment. Also trends toward a greater
      percentage of calories from total and saturated fat at the expense of
      carbohydrates, a decrease in fiber intake, and an improvement in the calcium to
      phosphorus ratio were seen. Bone metabolism, and therefore tooth movement may be
      affected by copper and manganese levels. Thus, to optimize patient physiologic
      response to orthodontic treatment, it may be beneficial to provide nutritional
      guidance to patients in choosing soft food diets.

PMID- 9155816
TI  - Comparison of two dental devices for treatment of obstructive sleep apnea
      syndrome (OSAS).
AB  - Previous case reports have indicated dental devices can be an effective
      nonsurgical treatment for snoring and obstructive sleep apnea. This pilot study
      evaluated the effectiveness of two intraoral devices in reducing the Respiratory
      Disturbance Index (RDI) and Epworth Sleepiness Scale (ESS) scores in a group of
      24 adult volunteers with a history of loud snoring. Subjects were randomly
      assigned to two groups. Twelve subjects were fitted with a dental device designed
      to increase vertical dimension and protrude the mandible (device A). The other 12
      subjects received a different device designed to minimally increase vertical
      opening without protruding the mandible (device B). Unattended home sleep
      monitoring (Edentrace II Digital Recorder, Edentech Corp.) was used to compute
      RDI at two time periods: (T0) before using any dental device and (T1) while using
      a dental device 2 weeks after the initial delivery date. The mean RDI and ESS
      scores at T0 for subjects in the device A group were 35.6 +/- 28.4 and 12.0 +/-
      3.9, respectively. Means for the same measures at T1 were 21.1 +/- 21.4 and 8.2
      +/- 4.0. For subjects in the device B group, means for RDI and ESS scores at T0
      were 36.5 +/- 43.7 and 13.0 +/- 4.5, the means at T1 were 46.8 +/- 47.0 and 12.5
      +/- 5.7. The effectiveness of the two devices was estimated by comparing the
      difference in RDI scores from T0 to T1 for the 10 subjects who were using device
      A and completed the study and the 8 subjects who were using device B and
      completed the study. Six subjects withdrew for various reasons. From T0 to T1,
      device A reduced RDI scores in 9 of 10 subjects, with a mean reduction in RDI of
      14.5 (p < or = 0.05) and in ESS score of 3.8 (p < or = 0.005). Device B showed no
      change or an increased RDI score in 8 of 8 subjects. Seven of the eight subjects
      who showed no improvement in RDI with device B were then fitted with device A.
      Four of these seven subjects showed a reduction in RDI and five showed a
      reduction in ESS after using device A for 2 weeks. The mean reduction in RDI and
      ESS was 2.4 +/- 19.8 and 2.4 +/- 3.0, respectively. Hence, we conclude that a
      dental device that advances the mandible and increases the vertical dimension to
      open the upper airway is more effective in reducing the number of apneic and
      snoring events during sleep than one which does not.

PMID- 9155818
TI  - Windows 95: troubles and trouble shooting.

PMID- 9155819
TI  - Litigation, legislation, and ethics. Are you a doctor or are you a dentist?

PMID- 9155821
TI  - The use of standardized allergen extracts. American Academy of Allergy, Asthma
      and Immunology (AAAAI)

PMID- 9155820
TI  - Potential role of tachykinins in inflammatory diseases.

PMID- 9155822
TI  - House dust mite allergen levels in public places in New Zealand.
AB  - BACKGROUND: House dust mite allergens are a risk factor for asthma in New
      Zealand, and levels in domestic dwellings have been found to be high compared
      with levels in most other countries. Studies in other countries have demonstrated
      lower levels of Dermatophagoides pteronyssinus allergens in public places
      compared with levels in domestic dwellings. OBJECTIVES: The purpose of this study
      was to measure reservoir Der p 1 levels in public places in New Zealand and to
      examine determinants of these levels. METHODS: Reservoir dust was obtained in the
      two centers (Christchurch and Wellington) from hotels, hospitals, rest homes,
      churches, primary schools, childcare centers, cinemas, bank head offices, and
      airplanes; samples were also obtained from ski lodges. Single measurements of
      temperature and relative humidity were taken with thermohygrometers and an
      average humidity over 2 weeks was estimated with use of waxed wooden sticks.
      Information was collected on building construction, type of heating, and
      frequency of cleaning. Der p 1 levels (micrograms per gram of fine dust) for
      floor (n = 202), bed (n = 65), and seat (n = 24) samples in public places were
      expressed as geometric means (95% confidence intervals). RESULTS: Der p 1 levels
      in public places were significantly lower than domestic levels in both Wellington
      and Christchurch. Both floor and bed levels were higher in hotels than in other
      public places. After controlling for potential confounders, floor Der p 1 levels
      were higher with carpeted floors (p < 0.0001) and lower with recent cleaning (p =
      0.02) and bed Der p 1 levels were higher with timber wall construction (p =
      0.03). Other building, heating, or cleaning characteristics did not show
      significant association with allergen levels. CONCLUSION: Der p 1 levels were
      much lower in public places than in domestic dwellings with floor levels
      primarily affected by floor covering.

PMID- 9155823
TI  - Sensitization to inhaled allergens as a risk factor for asthma and allergic
      diseases in Chinese population.
AB  - BACKGROUND: Allergen sensitization is associated with asthma and allergic disease
      in children, but such a relationship has not been confirmed in Chinese
      populations. OBJECTIVES: The objective of this study was to evaluate the effects
      of allergen sensitization and family history of atopy on asthma and allergic
      disease in Chinese schoolchildren from three southeast Asian populations.
      METHODS: Written questionnaires on respiratory and allergic symptoms were
      completed by parents of children of secondary-school age (age range 12 to 18
      years) in Hong Kong (n = 1062), Kota Kinabalu in eastern Malaysia (n = 409), and
      San Bu in southern China (n = 737). A subsample of school-children underwent skin
      prick testing to common inhalant allergens (Hong Kong 471 children, Kota Kinabalu
      321, San Bu 647). RESULTS: The prevalence of asthma and allergic disease in
      schoolchildren was highest in Hong Kong, intermediate in Kota Kinabalu, and
      lowest in San Bu. However, the overall rate of atopic sensitization was similar
      in the three populations (49% to 63%). House dust mite and cockroach were the two
      most common allergens causing sensitization and these gave rise to more than 95%
      of the positive skin test results in all three populations. By regression
      analysis, mite allergy was associated with rhinitis and asthma in all three
      populations, and a family history of asthma, rhinitis, or eczema was strongly
      associated with respective symptoms in the subjects. After adjusting for age,
      sex, atopic status, and family history of allergic disease, the place of
      residence remained a significant independent factor for asthma (odds ratio [OR] =
      1.0 for Hong Kong, 0.57 for Kota Kinabalu, 0.15 for San Bu, p < 0.001), rhinitis
      (OR = 1.0 for Hong Kong, 0.59 for Kota Kinabalu, 0.15 for San Bu, p < 0.001), or
      eczema (OR = 1.0 for Hong Kong, 0.35 for Kota Kinabalu, 1.01 for San Bu, p <
      0.001). CONCLUSION: Sensitization to indoor allergens was a significant risk
      factor for asthma and allergic disease, and familial clustering of disease was
      common in the region. However, the marked difference in disease prevalence in the
      three southeast Asian populations of Chinese schoolchildren cannot be explained
      by atopic sensitization and family history alone, and the place of residence was
      an independent risk factor for asthma and allergies, which suggests an important
      environmental role in disease pathogenesis.

PMID- 9155824
TI  - Factors that influence the presence of symptoms caused by latex allergy in
      children with spina bifida.
AB  - BACKGROUND: Some children with spina bifida who are sensitized to latex can have
      severe reactions, whereas others remain free of symptoms. OBJECTIVE: Our aim was
      to study the differences between these two groups of patients. MATERIAL AND
      METHODS: In 110 consecutive children with spina bifida, we identified by means of
      skin prick tests and serum latex-specific IgE 32 patients sensitized to latex. In
      these 32 patients, data were collected for sex, age, personal and familial
      history of atopy, number of cystourethrograms and number of operations, history
      of intermittent bladder catheterization, serum levels of total IgE in units per
      milliliter and in z units, levels of latex-specific IgE, and results of skin
      prick tests. RESULTS: Sixteen patients (50%) had clinical symptoms related to
      latex. These patients had significantly higher levels of serum specific IgE (32.8
      +/- 30.7 U/ml vs. 12.8 +/- 16.5 U/ml), were more likely to have positive
      responses on skin tests (100% vs. 75%), had a higher number of operations (10.5
      +/- 6.9 vs. 5.8 +/- 2.7), and were more likely to have a personal history of
      atopy (44% vs. 6%) in comparison with findings for patients who did not have
      symptoms (p < 0.05 in all cases). A multivariate logistic regression analysis
      identified the latter two factors as independent synergistic variables to predict
      symptoms. CONCLUSIONS: The number of operations is the main risk factor for latex
      related symptoms in sensitized children. Atopy seems to lower the threshold both
      for sensitization and for the presentation of clinical reactions.

PMID- 9155826
TI  - Sensitization to hen's egg at the age of twelve months is predictive for allergic
      sensitization to common indoor and outdoor allergens at the age of three years.
AB  - BACKGROUND: Specific predictors for atopic sensitization in early infancy are
      prerequisites for preventive intervention studies. OBJECTIVE: To identify
      predictors of allergic sensitization to common aeroallergens in infancy, 1314
      children in five German cities were followed up from birth (1990) to the age of 3
      years. METHODS: Blood samples were taken from cord blood and at follow-up visits
      at the ages of 1, 2, and 3 years. Total serum IgE and specific IgE antibodies to
      common food and inhalant allergens were determined. RESULTS: Among our study
      population, risk factors for sensitization to indoor and/or outdoor allergens at
      the age of 3 years were a positive family history, the presence of hen's egg
      specific IgE antibodies (> or = 0.35 kU/L), and increased log- [total IgE] levels
      at the age of 12 months. Elevated cord blood IgE was not associated with
      sensitization to inhalant allergens at the age of 3 years. Egg-specific IgE
      greater than 2 kU/L in combination with a positive family history of atopy was a
      highly specific (specificity, 99%) and predictive (positive predictive value,
      78%) marker for sensitization to inhalant allergens at 3 years of age.
      CONCLUSIONS: Hen's egg-specific IgE at the age of 12 months is a valuable marker
      for subsequent allergic sensitization to allergens that cause asthma, allergic
      rhinitis, and atopic dermatitis.

PMID- 9155827
TI  - Lower airway responses to rhinovirus-Hanks in healthy subjects with and without
      allergy.

PMID- 9155825
TI  - Perception of airway obstruction in asthma: sequential daily analyses of
      symptoms, peak expiratory flow rate, and mood.
AB  - BACKGROUND AND OBJECTIVE: Studies have demonstrated a weak correlation between
      the degree of airways obstruction and the severity of asthma symptoms. Although
      the causes for this disparity are probably multiple, mood has been hypothesized
      to modulate symptoms. This investigation was designed to evaluate the effect of
      mood and other patient characteristics on the perception of airways obstruction.
      METHODS: We compared mood variables, symptom severity, albuterol use, and peak
      expiratory flow rate (PEFR) measured three times daily over a 21-day period in 21
      adults with moderate to severe asthma. Electronic equipment was used for data
      collection. Analyses included both individual patient assessments and a within
      subjects, time series, pooled regression of concurrent and time-lag data.
      RESULTS: After pooling 1323 observations, there was a weak concurrent
      relationship between symptoms and PEFR (beta = -0.17, p < 0.001). Only five
      patients (24%) were accurate perceivers, defined by a statistically significant
      relationship between symptoms and PEFR across time. Higher forced expiratory flow
      at 25% to 75% of capacity predicted perception accuracy (p = 0.004); active mood
      was marginally associated with accuracy (p = 0.06). These two variables together
      explained 41% of the variation in perception accuracy (p = 0.004). Mood did not
      independently predict symptoms, but conversely, increased symptoms predicted less
      pleasant mood (beta = 0.08, p < 0.001), less active mood (beta = -0.11, p <
      0.001), and less active-pleasant mood (beta = 0.06, p < 0.001). PEFR did not
      predict mood, and only pleasant mood independently predicted higher PEFR (beta =
      0.04, p < 0.05). Symptoms, but not PEFR, were concurrently associated with
      albuterol use (beta = 0.24, p < 0.001). CONCLUSION: The relationship between
      changes in PEFR and symptoms over time was generally poor. Those patients with
      lower FEF25-75 values tended to be less accurate perceivers. Mood states were
      influenced by asthma symptoms, but the converse was not true.

PMID- 9155828
TI  - Inhibitory effect of indomethacin on tachyphylaxis in response to acetaldehyde
      induced bronchoconstriction in patients with asthma.
AB  - BACKGROUND: Acetaldehyde, a main factor in alcohol-induced asthma, causes
      bronchoconstriction indirectly through histamine release; and tachyphylaxis in
      response to repeated inhalation of acetaldehyde is observed in patients with
      asthma. OBJECTIVE: The study was designed to clarify the mechanism of
      tachyphylaxis in response to acetaldehyde-induced bronchoconstriction. METHODS:
      We investigated the bronchial response to inhaled acetaldehyde in 10 patients
      with asthma who were treated with indomethacin in a double-blind, randomized,
      placebo-controlled, crossover fashion. RESULTS: The mean acetaldehyde
      concentration causing a 20% fall in FEV1 with placebo increased significantly
      from 13.0 mg/ml (geometric SEM = 0.115) to 31.1 mg/ml (geometric SEM = 0.069)
      over a period of 1 hour (p < 0.01), whereas there was a slight but not
      significant tachyphylaxis during indomethacin treatment. The tachyphylactic
      effect, expressed as logarithmic value of the second PC20 minus logarithmic value
      of the first PC20, was significantly (p < 0.05) reduced from 0.380 (0.066) with
      placebo treatment to 0.148 (0.094) with indomethacin treatment. CONCLUSION: These
      results suggest an important role of cyclooxygenase pathway products in decreased
      response to repeated inhalation of acetaldehyde in patients with asthma.

PMID- 9155829
TI  - Increased levels of nitric oxide derivatives in induced sputum in patients with
      asthma.
AB  - BACKGROUND: Nitric oxide (NO) plays an important role as an inflammatory mediator
      in the airways. However, because direct measurement of endogenous NO has been
      difficult in vivo, the exact pathologic roles of NO in human airway inflammation
      have remained unclear. OBJECTIVE: This study was designed to determine whether NO
      may be harmful by amplifying allergic inflammation in asthmatic airways. METHODS:
      In this study we examined the concentration of stable end products of NO, nitrite
      and nitrate, in induced sputum in 18 patients with asthma and 10 normal control
      subjects and evaluated the relationship between levels of NO derivatives in
      sputum and cellular and biochemical profiles, the degree of airflow obstruction,
      and the cytotoxic activities for epithelial cells. RESULTS: The concentration of
      NO derivatives in induced sputum was significantly higher in patients with asthma
      than in normal control subjects (1086 +/- 325 mumol/L, 577 +/- 115 mumol/L; p <
      0.05). Percentages of eosinophil counts and eosinophil cationic protein levels in
      sputum were also significantly higher in patients with asthma. Moreover,
      percentages of eosinophil counts and eosinophil cationic protein levels in sputum
      in patients with asthma were significantly correlated with the concentration of
      NO derivatives in sputum (r = 0.63, p < 0.01; r = 0.56, p < 0.05, respectively).
      In addition, we found that the concentration of NO derivatives in sputum in
      patients with asthma was significantly correlated with the degree of airflow
      obstruction (FEV1/forced vital capacity) (r = -0.62, p < 0.01) and with
      percentages of shedding epithelial cells (r = 0.61, p < 0.01). CONCLUSION: We
      have shown that a higher concentration of NO derivatives was found in induced
      sputum of patients with asthma as compared with normal subjects. The clinical
      implication of our findings is that measurement of NO derivatives in induced
      sputum may be useful for assessing allergic inflammation in airways.

PMID- 9155830
TI  - Hornet venom allergen antigen 5, Dol m 5: its T-cell epitopes in mice and its
      antigenic cross-reactivity with a mammalian testis protein.
AB  - BACKGROUND: A major venom allergen of white-faced hornet (Dolichovespula
      maculata) is antigen 5, Dol m 5. It is a 204-residue protein having 23% to 35%
      sequence identity with several proteins from diverse sources. The biologic
      function of antigen 5 and its sequence-related proteins is not known. OBJECTIVE:
      This study was done to delineate the T-cell epitopes of Dol m 5 and to test their
      cross-reactivity with a sequence-related mouse testis protein, tpx. METHODS: T
      cell epitope mapping and cross-reactivity were studied with 15- or 20-residue
      peptides by their stimulation of spleen cells from mice immunized with
      recombinant Dol m 5 or tpx fragments. RESULTS: Three of 20 peptides studied were
      found to represent major T-cell epitopes of Dol m 5, being recognized by five or
      all of six mouse strains tested. One major epitope peptide, residue 176-195,
      showed cross-reactivity in BALB/c mice with the homologous antigen 5s from yellow
      jackets and wasps, as well as with mouse tpx. The cross-reactivity of Dol m 5 and
      mouse tpx is not reciprocal because spleen cells from tpx-immunized mice were
      stimulated by the hornet peptide, but cells from Dol m 5-immunized mice were not
      stimulated by the corresponding tpx peptides. CONCLUSION: Cross-reactivity of
      vespid antigen 5 and mouse tpx may be of importance in insect allergy because
      human and mouse testis proteins are highly homologous.

PMID- 9155831
TI  - Platelet-activating factor induces histamine release from human skin mast cells
      in vivo, which is reduced by local nerve blockade.
AB  - BACKGROUND: Intradermal injection of platelet-activating factor (PAF) causes
      wheal and flare reactions, which are inhibited by antihistamines. However, PAF
      does not release histamine from human dispersed skin mast cells in vitro. The
      purpose of this study was to investigate the extent and possible mechanisms of
      PAF-induced histamine release in human skin in vivo with the use of dermal
      microdialysis. METHODS: Hollow dialysis fibers were inserted into the upper
      dermis in forearm skin and each fiber was perfused with Krebs-Ringer bicarbonate
      solution at a rate of 3.0 microliters/min. PAF (4.5 to 36 mumol/L), lyso-PAF (36
      mumol/L), vehicle (negative control), and codeine 750 or 250 mumol/L (positive
      control) were injected intradermally above separate fibers. Dialysate was
      collected in 2-minute fractions for 20 minutes and histamine analyzed
      spectrofluorometrically. RESULTS: PAF, but not lyso-PAF, caused statistically
      significant dose-related histamine release and wheal and flare reactions.
      Intradermal mepivacaine administration significantly abrogated flare reactions by
      PAF and codeine and inhibited histamine release and wheal reactions by PAF but
      not by codeine. Long-term topical capsaicin administration inhibited histamine
      release and wheal reactions by PAF but not by codeine. It inhibited flare
      reactions induced by both compounds. PAF did not release histamine from blood
      basophils. CONCLUSIONS: These data suggest that PAF induced histamine release
      from mast cells in intact human skin indirectly via neurogenic activation.
      Further, on the intradermal injection of PAF histamine release and the skin
      responses, the wheal and the flare, are differentially regulated by neurogenic
      components.

PMID- 9155833
TI  - Elevated expression of messenger ribonucleic acid encoding IL-13 in the bronchial
      mucosa of atopic and nonatopic subjects with asthma.
AB  - Local secretion of cytokines by T cells within the bronchial mucosa, with
      consequent selective eosinophil influx, has been implicated in the pathogenesis
      of bronchial asthma. The cytokine IL-13 exhibits activities (selective eosinophil
      vascular adhesion by very late antigen-4/vascular cell adhesion molecule-1
      interaction and promotion of IgE synthesis and "T112-type" T cell responses) that
      may be relevant to this process. We hypothesized that, compared with conditions
      in control subjects, elevated expression of messenger ribonucleic acid (mRNA)
      encoding IL-13 is a feature of the bronchial mucosa of both atopic (positive skin
      prick test result to at least one of a range of common aeroallergens) and
      nonatopic (negative skin prick test results and serum total IgE concentrations
      within the normal range) subjects with asthma. With use of a semiquantitative
      reverse transcriptase-polymerase chain reaction technique, we measured the
      quantities (relative to beta-actin) of IL-13 mRNA in bronchial mucosal biopsy
      specimens from atopic and nonatopic subjects with asthma and atopic and nonatopic
      control subjects. Biopsy specimens from the subjects with asthma, whether the
      subjects were atopic or nonatopic, had statistically equivalent quantities of IL
      13 mRNA relative to beta-actin, and these quantities were significantly elevated
      compared with those in specimens from both the atopic and nonatopic control
      subjects (p < or = 0.02 in each case), in which the quantities of IL-13 mRNA
      relative to beta-actin were also statistically equivalent. The quantities of IL
      13 mRNA reflected the numbers of EG2+ eosinophils per unit area of submucosa in
      the biopsy specimens as determined by immunohistochemistry, which were
      statistically equivalent in the atopic and nonatopic subjects with asthma and
      significantly elevated as compared with those in both the atopic and nonatopic
      control subjects without asthma (p < or = 0.007 in each case). Taking the
      subjects with asthma as a group, no correlations were observed between the
      quantities of IL-13 mRNA (relative to beta-actin) and several measures of disease
      severity. These data are consistent with the hypothesis that IL-13 plays a role
      in the pathogenesis of both atopic and nonatopic asthma, at least partly through
      promoting recruitment of eosinophils to the bronchial mucosa, although other
      factors may be more important in regulating the severity of the disease.

PMID- 9155832
TI  - Regulation of alpha 4 integrin-mediated adhesion of human eosinophils to
      fibronectin and vascular cell adhesion molecule-1.
AB  - BACKGROUND: Eosinophils selectively accumulate at sites of allergic inflammation.
      Their recruitment is dependent on both the expression and functional activity of
      cell adhesion molecules. How the functional activity of cell adhesion molecules
      on eosinophils is regulated is poorly understood. OBJECTIVE: Our objective was to
      examine the functional activity of alpha 4 integrins on human eosinophils and its
      regulation by various agents. METHODS: Function of alpha 4 integrins on human
      eosinophils was examined by testing adhesion to immobilized fibronection and
      vascular cell adhesion molecule-1 (VCAM-1) in the presence or absence of a
      monoclonal antibody (mAb) (8A2) that activates beta 1 integrin function. RESULTS:
      Spontaneous eosinophil adhesion to VCAM-1 was enhanced by 8A2, but adhesion to
      fibronectin could only be detected in the presence of 8A2. Concentrations of 8A2
      that were approximately 100-fold less than saturating induced maximal eosinophil
      adhesion. Adhesion to VCAM-1 in the presence of 8A2 was effectively inhibited by
      alpha 4 and beta 1 integrin mAbs: beta 7 mAb had partial inhibitory activity.
      Connecting segment-1 peptide and alpha 4 mAb blocked 8A2-dependent fibronectin
      binding: beta 1, beta 2, and beta 7 integrin mAbs had partial inhibitory
      activity. Eosinophils obtained from bronchoalveolar lavage fluids and blood
      eosinophils stimulated with IL-5, platelet-activating factor, or RANTES displayed
      increased beta 2 integrin-dependent, not alpha 4 integrin-dependent, attachment.
      Spontaneous adhesion of eosinophils to VCAM-1 was significantly reduced by the
      tyrosine kinase inhibitor tyrphostin B46 (inhibitory concentration of 50%
      approximately equal to 20 mumol/L); this effect was reversed by 8A2. CONCLUSIONS:
      The functional activity of integrins on eosinophils can be positively and
      negatively regulated. Altered integrin avidity may influence eosinophil
      recruitment in vivo.

PMID- 9155834
TI  - Upregulation of alpha GM-CSF-receptor in nonatopic asthma but not in atopic
      asthma.
AB  - BACKGROUND: Intrinsic asthma is characterized by an increased number of activated
      eosinophils and macrophages and an increased expression of the hematopoietic
      growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) in the
      bronchial mucosa. OBJECTIVE: This study was carried out to investigate the
      expression of alpha GM-CSF receptor (alpha GM-CSFr) messenger RNA and protein in
      the bronchial mucosa of patients with intrinsic or atopic asthma and of control
      subjects and to correlate the expression of alpha GM-CSFr to the number of EG2+
      cells (eosinophils) and CD68+ cells (macrophages) and pulmonary function.
      METHODS: Nineteen patients with stable asthma (9 with atopic and 10 with
      intrinsic asthma) and 22 normal control subjects (12 atopic and 10 nonatopic
      subjects) were recruited, and FEV1 (percent predicted) and PC20 were measured
      before bronchoscopy. Endobronchial biopsy specimens were obtained and examined
      for membrane-bound alpha GM-CSFr by using in situ hybridization and
      immunocytochemistry. RESULTS: alpha GM-CSFr mRNA- and protein-positive cells were
      identified in biopsy specimens from all four groups studied. There was no
      significant difference in the number of cells expressing alpha GM-CSFr mRNA and
      protein in patients with atopic asthma compared with atopic and nonatopic control
      subjects. However, the numbers of alpha GM-CSFr mRNA- and protein-positive cells
      were significantly higher in nonatopic patients with asthma compared with atopic
      patients with asthma and atopic and nonatopic control subjects (p < 0.001). In
      the patients with intrinsic asthma, the number of alpha GM-CSFr mRNA-positive
      cells per millimeter of basement membrane correlated with numbers of CD68+ cells
      (r2 = 0.87, p < 0.001) but not with EG2+ cells, and colocalization studies
      demonstrated that 80% of the cells expressing alpha GMCSFr mRNA were CD68+. The
      expression of GM-CSF was also significantly increased in patients with intrinsic
      asthma compared with those with atopic asthma and control subjects (p < 0.05). In
      addition, in intrinsic asthma, there was a correlation between alpha GM-CSFr mRNA
      and FEV1 (r2 = 0.61, p < 0.05). CONCLUSION: These results demonstrate that
      elevated numbers of cells expressing alpha GM-CSFr can be detected in nonatopic
      asthma but not in atopic asthma and suggest that this increased expression is
      predominantly macrophage-associated and may play an important pathophysiologic
      role in intrinsic asthma.

PMID- 9155835
TI  - Predominance of type 2 cytokine-producing CD4+ and CD8+ cells in patients with
      atopic dermatitis.
AB  - BACKGROUND: Recently, increased IL-4 and decreased interferon-gamma (IFN-gamma)
      production in peripheral blood mononuclear cells (PBMCs) from patients with
      atopic dermatitis have been reported by several groups. They measured the total
      amount of each cytokine in culture supernatants in their studies. These studies
      suggested a predominance of type 2 cytokine-producing cells in atopic dermatitis.
      However, it is still unclear whether the cytokine imbalance is the result of an
      imbalance of specific T-cell subsets or of dysregulation of the cytokine
      producing ability in T-cell subsets. Here, we examined frequencies of IL-4-, IFN
      gamma-, or IL-2-producing CD4+ cells and CD8+ cells in PBMCs from patients with
      atopic dermatitis at a single cell level by using flow cytometry. METHODS: PBMCs
      from 45 patients with atopic dermatitis and 24 healthy control subjects were
      stimulated with immobilized anti-CD3 monoclonal antibody for 6 hours in the
      presence of monensin. Cells were fixed, made permeable, and stained for
      intracellular cytokines in combination with staining for cell surface markers CD4
      and CD8. RESULTS: The frequency of IL-4-producing CD4+ cells and CD8+ cells from
      patients with atopic dermatitis was significantly higher (p < 0.001) than that
      from healthy control subjects. In contrast, the frequency of IFN-gamma-producing
      CD4+ cells and CD8+ cells was significantly decreased (p < 0.01) in the patients
      with atopic dermatitis. The frequency of IL-2-producing cells from patients with
      atopic dermatitis was comparable to that from healthy control subjects.
      CONCLUSION: Our findings indicate that frequencies of type 2 cytokine-producing
      cells, not only among CD4+ cells but also among CD8+ cells, were significantly
      higher in patients with atopic dermatitis than in healthy control subjects.

PMID- 9155836
TI  - Dermal eosinophils in atopic dermatitis undergo cytolytic degeneration.
AB  - BACKGROUND: Immunofluorescent staining for eosinophil granule proteins in
      lesional skin of patients with atopic dermatitis shows extensive extracellular
      deposition throughout the upper dermis with relatively few intact eosinophils.
      OBJECTIVE: This study was carried out to determine whether eosinophil granule
      protein deposition in atopic dermatitis occurs by classical exocytosis, by
      piecemeal degranulation, or as a result of cytolysis. METHODS: Skin biopsy
      specimens from 10 patients with atopic dermatitis were examined by electron
      microscopy. RESULTS: The biopsy specimens showed varying degrees of dermal
      eosinophil granule major basic protein deposition by indirect immunofluorescence.
      Specimens from seven patients showed striking alterations of eosinophils by
      electron microscopy including intact eosinophils with granule alterations
      (reversal of core staining and/or core lucency) and with uropod processes. Biopsy
      specimens from six patients showed evidence of eosinophil degeneration with
      disruption of nuclear and/or plasma membranes. In four patients' specimens,
      membrane-bound eosinophil granules were present near degenerating eosinophils or
      were present in the absence of recognizable eosinophils. Evidence of classical
      exocytotic degranulation was not observed. Two of the specimens were also
      examined by immunoelectron microscopy for major basic protein localization. In
      these, major basic protein appeared to be lost from the granule core and
      distributed in the eosinophil cytoplasm as granules disintegrated and the cell
      disrupted. CONCLUSION: These findings support the hypothesis that eosinophils
      undergo cytolysis with release of granule contents and membrane-bound granules;
      this is likely the usual mechanism of eosinophil granule protein release in
      atopic dermatitis.

PMID- 9155838
TI  - Expression of high-affinity IgE receptors (Fc epsilon RI) on peripheral blood
      basophils, monocytes, and eosinophils in atopic and nonatopic subjects:
      relationship to total serum IgE concentrations.
AB  - BACKGROUND: High-affinity IgE receptors (Fc epsilon RI) have been identified on
      peripheral blood basophils, monocytes, and eosinophils; but the relative receptor
      expression on these cells and their relationship to atopy are unclear. OBJECTIVE:
      The aim of this study was to compare Fc epsilon RI expression on these cell types
      and assess their relationship to total serum IgE concentrations in subjects with
      atopic asthma, rhinitis, or dermatitis compared with nonatopic control subjects.
      METHODS: Flow cytometry was used to evaluate Fc epsilon RI expression by
      determining the specific mean fluorescence of the binding of two anti-Fc epsilon
      RI alpha-chain monoclonal antibodies (15-1, which competes with IgE for receptor
      binding, and 22E7, which is noncompetitive). RESULTS: Compared with basophils Fc
      epsilon RI expression (determined by 22E7 specific mean fluorescence) was greatly
      reduced on monocytes and was only detectable on eosinophils in a small minority
      of subjects. Nevertheless, Fc epsilon RI expression on all three cell types was
      significantly increased in atopic patients compared with nonatopic control
      subjects (p < 0.0001 for basophils, p = 0.003 for monocytes, and p = 0.039 for
      eosinophils). Fc epsilon RI expression on both basophils and monocytes in all
      subjects correlated significantly with serum IgE concentrations (r = 0.86 and
      0.55, respectively; p < 0.001). For each subject, and on all three cell types,
      the specific mean fluorescence after 22E7 staining was greater than with 15-1,
      implying some degree of receptor occupancy. CONCLUSION: Fc epsilon RI expression
      on peripheral blood monocytes was considerably less than on basophils and barely
      detectable on eosinophils. Elevated Fc epsilon RI expression was observed in
      atopic subjects with all three cell types, suggesting a role for these receptors
      in IgE-mediated allergic inflammation. The possibility of common regulatory
      mechanisms was suggested by the correlation of Fc epsilon RI expression on
      basophils and monocytes with serum IgE concentrations.

PMID- 9155841
TI  - Analysis of rat serum allergens.

PMID- 9155837
TI  - Late response to allergen is associated with increased concentrations of tumor
      necrosis factor-alpha and IL-5 in induced sputum.
AB  - Bronchial antigen challenge of sensitized atopic patients with asthma results in
      an early fall in FEV1, followed in a proportion of patients by a late (4 to 24
      hours) fall. The late response is accompanied by an increase in bronchial
      reactivity, which is widely believed to reflect local influx and degranulation of
      inflammatory cells, particularly eosinophils, in association with elevated local
      secretion of cytokines. We hypothesized that the development of a late-phase
      bronchoconstrictor response and airway eosinophilia after allergen challenge of
      sensitized atopic patients with asthma is associated with elevated induced sputum
      concentrations of the eosinophil-active cytokines IL-5 and granulocyte-macrophage
      colony-stimulating factor and the proinflammatory cytokine tumor necrosis factor
      alpha. We counted inflammatory leukocytes and measured cytokine concentrations in
      induced sputum at baseline and 24 hours after inhalational allergen challenge of
      15 atopic patients with asthma who had previously demonstrated a late response.
      We observed significant increases in the numbers of eosinophils and the
      concentrations of their granule products, eosinophil cationic protein and
      eosinophil peroxidase. In contrast, the numbers of neutrophils and concentrations
      of two of their products, myeloperoxidase and human neutrophil lipocalin, did not
      significantly change. The numbers of sputum eosinophils correlated with the
      maximal late-phase fall in FEV1. Concentrations of IL-5 and tumor necrosis factor
      alpha, but not granulocyte-macrophage colony-stimulating factor, were
      significantly elevated after allergen challenge. We conclude that the relatively
      noninvasive technique of induced sputum production can be used to monitor the
      effect of bronchial provocation on cytokine concentrations in asthma.

PMID- 9155839
TI  - Altered expression of IgG and complement receptors indicates a significant role
      of phagocytes in atopic dermatitis.
AB  - BACKGROUND: Strict dietary precautions against allergic sensitization may benefit
      a group of predisposed children. OBJECTIVE: To develop new strategies for
      identifying these children, a better understanding of the processes that initiate
      sensitization and regulate and perpetuate the inflammatory response is needed.
      METHODS: We measured the expression of the receptors for the constant (Fc) region
      of IgG (Fc gamma RI, Fc gamma RII, and Fc gamma RIII) and that for the complement
      fragments C3b and C3bi (CR1 and CR3) in neutrophils and monocytes from 39
      children with atopic dermatitis, 17 disease control patients with acute
      infections, and 17 healthy control subjects. The capacity of phagocytes to
      produce reactive oxygen species was also determined. To find the best way of
      discriminating the patients with atopic dermatitis from control subjects, a
      stepwise logistic binary regression model was made. RESULTS: The stepwise
      logistic regression analysis was based on differences in individual receptor
      expression between the study groups. Because acute infections strongly affected
      receptor expression in both neutrophils and monocytes, to avoid diagnostic bias,
      children with acute infections were excluded from the analysis. The combination
      of the receptors CR1 in neutrophils and Fc gamma RI and Fc gamma RII in monocytes
      was the best indicator of atopic dermatitis. A significant correlation between
      the expression of CR1 in neutrophils and in monocytes, as well as reactive oxygen
      species production of phagocytes, and the severity of the eczema was detected.
      CONCLUSIONS: These results suggest that a distinct receptor profile of phagocytic
      cells can be characterized in patients with atopic dermatitis, providing a new
      direction to the search for early identification of children predisposed to
      allergic sensitization.

PMID- 9155840
TI  - Cutaneous allergy to recombinant human type I IL-1 receptor (rhu IL-1RI).

PMID- 9155842
TI  - Carrot-induced asthma: immunodetection of allergens.

PMID- 9155844
TI  - Cumin anaphylaxis: a case report.

PMID- 9155845
TI  - Is cross-reactivity a real or an imaginary concept?

PMID- 9155843
TI  - Development of IgE antibody to gelatin in children with systemic immediate-type
      reactions to vaccines.

PMID- 9155847
TI  - Nebulizer therapy. Guidelines. British Thoracic Society Nebulizer Project Group.

PMID- 9155846
TI  - Current best practice for nebuliser treatment. The Nebulizer Project Group of the
      British Thoracic Society Standards of Care Committee.

PMID- 9155848
TI  - Overview of nebuliser treatment.

PMID- 9155851
TI  - Nebulisers for chronic obstructive pulmonary disease.

PMID- 9155852
TI  - Nebulisers for the elderly.

PMID- 9155849
TI  - The science of nebulised drug delivery.

PMID- 9155854
TI  - Nebulisers for patients with HIV infection and AIDS.

PMID- 9155853
TI  - Nebuliser therapy in the intensive care unit.

PMID- 9155850
TI  - Nebulisers for asthma.

PMID- 9155858
TI  - Nebulised drugs in palliative care.

PMID- 9155856
TI  - Nebulised antibiotics for adults with cystic fibrosis.

PMID- 9155857
TI  - Nebulisers for bronchiectasis.

PMID- 9155855
TI  - Nebulised bronchodilators, corticosteroids, and rhDNase in adult patients with
      cystic fibrosis.

PMID- 9155859
TI  - Nebuliser therapy in childhood.

PMID- 9155860
TI  - Nebulised bronchodilators, antibiotics and rhDNase for children with cystic
      fibrosis.

PMID- 9155862
TI  - Staff education.

PMID- 9155861
TI  - Selecting and using nebuliser equipment.

PMID- 9155863
TI  - Running a domiciliary nebuliser service.
AB  - A nebuliser service should be provided locally, according to local needs. It
      should be centralised and administered by a designated consultant or consultants
      and written guidelines should be provided for medical and para-medical staff. The
      service should: (1) provide compressor/nebuliser units suitable for the
      prescribed treatment, (2) provide a system for equipment replacement, repair and
      maintenance, and (3) show patients how to use the equipment and give them
      comprehensive written instructions.

PMID- 9155864
TI  - Neuroendocrine effects of cytokines in the rat.
AB  - The necessity ot maintain and/or restore homeostasis is an essential feature of
      mammals. This requires complex interactions between body cells, such as those
      from the immune and neuroendocrine systems, and in particular implies that the
      occurrence of immune activation be conveyed to the brain. It is now widely
      recognized that following infection, injury or inflammation, some immune cells
      (particularly macrophages) produce polypeptides called cytokines, interleukins or
      lymphokines /48/. These proteins provide the basis for intercellular
      communication between leukocytes (hence the name "interleukins") and mediate the
      immunoinflammatory responses (in particular T and B lymphocyte proliferation)
      /4,177/. In addition, interleukins (IL) can enter the general circulation and
      reach cells of the neuroendocrine axes, a phenomenon which represents one arm of
      the bidirectional communication links between the immune and the endocrine
      systems /25/. The early events which take place after presentation of an antigen
      (the so-called "acute-phase response" /89/) include metabolic and endocrine
      changes, such as changes in the circulating levels of insulin, TSH, GH, LH and
      ACTH, as well as adrenal and gonadal steroids /7,14/. This article reviews our
      present state of knowledge with regard to the hypothalamic-pituitary-adrenal
      (HPA) and hypothalamic-pituitary-gonadal (HPG) axes of the rodent in response to
      interleukins.

PMID- 9155865
TI  - Central behavioral effects of vasopressin: point and perspectives.

PMID- 9155866
TI  - Viruses and behavioural changes: a review of clinical and experimental findings.
AB  - This review focuses on behavioural neurovirology. Profound changes in behaviour
      are observed following infection of the central nervous system by some viruses.
      Irritability, insomnia, hyperactivity and learning disability are some of the
      behavioural disturbances that have been described in both humans and animals with
      central nervous system infection. The reticular core neurons which innervate the
      entire brain play an important role in regulating behaviour. Some of these
      neurons--locus coeruleus, raphe and diagonal bands--send projections to the
      olfactory bulbs and can be targets for exogenous agents attacking the olfactory
      epithelium. In infant rats, vesicular stomatitis virus is transported along the
      olfactory pathway by retrograde transport and reaches the reticular core neurons
      causing destruction of raphe, diagonal bands and, to a lesser extent, the locus
      coeruleus. As the neurons degenerate, the viral antigens disappear and the
      animals sustain severe deficits in neurotransmitter levels and behaviour. Such a
      "hit and run" effect of the virus suggests the possibility that a similar
      mechanism may be operating in some human disorders. Apart from their intrinsic
      interest as possible aetiological factors, viruses may provide valuable tools in
      experimental work seeking to correlate behaviour, morphology and neurotransmitter
      function.

PMID- 9155867
TI  - What can genetic models tell us about behavioral plasticity?
AB  - Biological diversity and learning have played an essential interactive role in
      the evolution of species, as intra-specific individual differences have exerted a
      buffering effect towards environmental changes, and learning ability per se has
      allowed their maintenance. By exploiting biological diversity individuals with
      defective learning and memory have been produced that allow the study of the
      neural substrates of encoding mechanisms, as has been done in studies from
      Drosophila to rodents. Various aspects of this neurogenetic approach are reviewed
      and pitfalls are indicated. It is clear that genetic models need to be
      implemented by an integrated multidisciplinary top-down approach based on
      behavioral, electrophysiological, histochemical, immunocytochemical and
      neurochemical techniques. Examples are presented from some animal models that
      illustrate how a systems level analysis of the neural substrates of information
      processing can be carried out using such an integrated scheme.

PMID- 9155868
TI  - Cerebral circulatory changes during migraine headache with aura.
AB  - Many authors report alterations of cephalic (both intracranial and extracranial)
      blood flow and vascular responsiveness in patients with migraine. In the majority
      of reports, rCBF has been decreased during the prodromal phase and increased
      during and immediately after the headache phase of migraine attacks. Abnormal
      vascular responsiveness has been demonstrated, not only during each attack, but
      also between attacks. Pharmacological and therapeutic evidence that many
      vasoactive agents induce, prevent or abolish attacks of migraine headache are
      consonant with the close relationships that exist between vascular abnormalities
      and the pathogenesis of migraine with aura. This is particularly true of the
      marked therapeutic effectiveness of calcium entry blockers, which are effective
      in the prophylaxis of migraine, and sumatriptan, which has direct
      vasoconstrictive effects, with relief of the headache, which lends strong support
      to a vascular hypothesis.

PMID- 9155869
TI  - Enhancer element, repetitive sequences and gene organization in an 8-kbp region
      containing the polyhedrin gene of the Spodoptera littoralis nucleopolyhedrovirus.
AB  - The Spodoptera littoralis multicapsid nucleopolyhedrovirus (SpliMNPV) shows only
      a distant genetic relationship to other NPVs. In this report we describe the gene
      organization of an 8-kbp region of the SpliMNPV which contains the polyhedrin
      gene. The polyhedrin transcription initiation sites were mapped and the sequence
      and gene organization of an 8-kbp region of SpliMNPV were determined. The
      sequences downstream of the polyhedrin gene showed colinearity with the gene
      organization of other NPVs. An anticlockwise 1035-bp open reading frame (ORF),
      capable of encoding a proline-rich polypeptide, was found at the 3' end of the
      polyhedrin gene. followed by an 837-bp ORF encoding a putative protein kinase
      (PK), with an orientation similar to that of the polyhedrin gene. Sequences
      upstream of the polyhedrin gene were found to be unique to SpliMNPV and contained
      two regions consisting of highly repetitive sequences. One region, 980 bp in
      length and termed sequence repeat region 1 (SR1), contained a variety of short
      direct repeats, SR1 was found to act as a transcriptional enhancer in a transient
      expression assay. Additional regions containing different repetitive sequences
      were identified within the proline-rich ORF1035 and in sequences located
      downstream of the pk gene.

PMID- 9155870
TI  - Identification and transcriptional analysis of pseudorabies virus UL6 to UL12
      genes.
AB  - We determined the nucleotide sequence of an 11059 bp fragment of the pseudorabies
      virus genome located in the right part of genomic BamHI fragment 3 and the
      adjacent part of BamHI fragment 6. Within this region eight open reading frames
      were identified whose deduced amino acid sequences exhibited homology to the UL6,
      UL7, UL8, UL8.5, UL9, UL10, UL11, and UL12 protein products of herpes simplex
      virus type 1. Transcriptional analyses indicated presence of 3'-coterminal mRNAs
      for genes UL8, UL8.5, and UL9 as well as for genes UL6 and UL7, respectively,
      while UL10 was represented by a very abundant unique transcript. Both gene
      arrangement and transcriptional organization within this region of the
      pseudorabies virus genome thus parallels the situation found in other
      alphaherpesviruses.

PMID- 9155871
TI  - Restriction of viral population by intravaginal infection of simian
      immunodeficiency viruses in macaque monkeys.
AB  - In order to examine whether the viral population is affected by intramucosal
      transmission, we analyzed the viral genotypes first detected in peripheral blood
      mononuclear cells (PBMCs) after intravaginal inoculation, before virus antibodies
      were detectable, and compared them with those in the inoculum. Three female
      cynomolgus macaques were inoculated intravaginally and a fourth was inoculated
      intravenously with polyclonal simian immunodeficiency viruses (SIVmac32H). The
      provirus genomes which first appeared in PBMC were sequenced in the V1 to V2
      region of the SIV envelope gene. A comparison of the sequences obtained from each
      monkey revealed a homogeneous or heterogeneous viral population depending on the
      infection route. In the intravenously inoculated monkey, the viral population was
      heterogenous and was similar to that in the virus inoculum. On the other hand, in
      the intravaginally inoculated monkeys, single genotypes (in two monkeys) and one
      genotype with a slight variation (in one monkey) were found, but they were
      different from each other, having no characteristic sequences in the V1 to V2
      region in common. None of the genotypes found in the PBMC were major genotypes in
      the virus inoculum. These results suggest that some selective mechanism, which
      differs among individuals, restricts the viral population during mucosal
      transmission.

PMID- 9155873
TI  - Differential sensitivity of culture and the polymerase chain reaction for
      detection of feline herpesvirus 1 in vaccinated and unvaccinated cats.
AB  - The diagnostic sensitivities of the polymerase chain reaction (PCR) and culture
      were compared and correlated with clinical signs in 5 vaccinated cats and 3
      unvaccinated cats that were experimentally infected with feline herpesvirus 1.
      Conjunctival swabs were taken each day from 0 to 14 days and on 21, 28 and 30
      days after challenge. PCR (49.3%) was significantly more sensitive than culture
      (30.1%) as assessed by an adjusted McNemar's test to account for non-independence
      of results between days within each cat (P = 0.02). PCR was considerably more
      sensitive (34.1%) than culture (8.2%) in vaccinated cats (P = 0.001), whereas
      there was no significant difference in sensitivities in the unvaccinated cats,
      where the sensitivity of PCR was 74.5% and that of culture was 66.7% (P = 0.17).
      In vaccinated cats showing clinical signs, the sensitivities of culture and PCR
      were 14.8% and 55.6% respectively (P = 0.03), whereas in unvaccinated cats the
      sensitivities were 80.6% and 96.8% respectively (P = 0.07). This study suggests
      that disease due to feline herpesvirus 1 has been significantly underdiagnosed,
      particularly in vaccinated cats.

PMID- 9155872
TI  - Generation of lymphoma-type variant hamster polyomavirus genomes in hamsters
      susceptible to lymphoma induction.
AB  - The hamster polyomavirus (HaPV) induces either hair follicle epitheliomas or
      lymphomas in either Z3 or HaP respectively. Syrian hamsters. In the lymphomas
      specifically deleted "lymphoma-type" (lt) HaPV genomes are accumulated. In the
      present study the temporal pattern of generation of HaPV (lt) DNA was
      investigated in context of the development of lymphomas in neonatally infected
      HaP hamsters. The generation of HaPV (lt) DNA was first detectable during the
      postnatal phase of high level replication of viral DNA in hemopoietic organs (at
      7 days post infection), thus clearly preceding the development of overt lymphoma.
      A variety of HaPV (lt) DNA species is generated in lymphoid cells, but usually
      only one of them is accumulated to high amounts in lymphoma cells. Furthermore,
      the pattern of HaPV (lt) and wild-type (wt) DNA was studied in normal and tumor
      tissues of tumor-bearing hamsters as well as in tumor-free hamsters. In tumor
      bearing hamsters predominantly HaPV (lt) DNA species were found in the infected
      tissues, while HaPV (wt) DNA was detected rarely and only in tumor-free tissues.
      In contrast, in tissues of tumor-free hamsters HaPV (wt) DNA prevailed over HaPV
      (lt) DNA species.

PMID- 9155874
TI  - Changes in the hemagglutinin molecule of influenza type A (H3N2) virus associated
      with increased virulence for mice.
AB  - The H3N2 influenza virus A/Philippines/82 (Phil82) and its bovine serum-resistant
      mutant, Phil82/BS, were used to investigate factors that influence virulence of
      influenza virus for mice. Phil82/BS, which lacks the high-mannose oligosaccharide
      at residue 165 of the hemagglutinin (HA) molecule, was found to replicate to a
      much higher titer in mouse lung than the parent Phil82, and had acquired
      lethality for mice. Further adaptation of Phil82/BS by sequential lung passage in
      mice yielded a strain of greater virulence, Phil82/BS/ML 10, in which a change at
      residue 246 of HA resulted in loss of a second potential glycosylation site.
      Phil82 is highly sensitive to neutralization in vitro by murine serum- and lung
      associated mannose-binding lectins (collectins). Characterization of the two
      mutant viruses indicated that resistance to murine collectins can account for the
      enhanced virulence of Phil82/BS but not for the further increase in virulence of
      Phil82/BS/ML10. Evidence is presented that residue 246 is not in fact
      glycosylated in Phil82/BS HA, nor presumably in the parent Phil82 virus. The HA
      molecule of Phil82/BS/ML10 displayed functional differences from Phil82/BS,
      including a change in the optimum pH of fusion and a minor change in receptor
      binding specificity, which may allow improved efficiency of replication in the
      mouse lung.

PMID- 9155875
TI  - Sequence analysis of the bovine herpesvirus type 1 genes homologous to the DNA
      polymerase (UL30), the major DNA-binding protein (UL29) and ICP18.5 assembly
      protein (UL28) genes of herpes simplex virus.
AB  - The nucleotide sequence of a 10.5 kb region (map position 0.332 to 0.410) of
      bovine herpesvirus type 1 (BHV-1) was determined. This region contained three
      open reading frames (ORFs) homologous to herpes simplex virus DNA polymerase
      catalytic subunit (DNApol, UL30), major DNA-binding protein (MDBP, UL29) and
      ICP18.5 assembly protein (ICP18.5, UL28). The BHV-1 DNApol. MDBP and ICP18.5 ORFs
      were 1246, 1203 and 826 amino acids long with a calculated molecular mass of
      134.2 kDa, 124.4 kDa and 86.9 kDa, respectively. They showed a high homology with
      alphaherpesvirus homologs despite large differences in the G + C content of the
      UL30-UL28 segment ranging from 44.4% for varicella zoster virus to 71.5% for BHV
      1. Particularly well conserved among Alphaherpesvirinae are the putative
      functional domains of the DNApol and MDBP proteins which are discussed.
      Phylogenetic analysis revealed that BHV-1 clustered in the Varicellovirus genus
      with the animal D-type viruses. In this group, the BHV-1 position was shown to
      vary according to the investigated genes. Indeed, pseudorabies virus clustered
      with BHV-1 in the DNApol tree but with equine herpesvirus 1 in the ICP18.5 tree.

PMID- 9155876
TI  - Genetic content of a 20.9 kb segment of human herpesvirus 6B strain Z29 spanning
      the homologs of human herpesvirus 6A genes U40-57 and containing the origin of
      DNA replication.
AB  - A continuous 20.9 kb sequence from human herpesvirus 6 variant B (HHV-6B) strain
      Z29 (GenBank accession number L16947) is genetically colinear with a discrete
      segment of the human cytomegalovirus (HCMV) UL region and with HHV-6 variant A
      (HHV-6A). Short nucleotide sequence determinations at multiple sites within an
      8.5 kb region immediately 3' to the 20.9 kb contig revealed additional
      colinearity between HHV-6B, HCMV and HHV-6A. Homology studies with the predicted
      peptide sequences from 11 complete and 12 partial HHV-6B open reading frames
      (ORFs) revealed that most encode proteins conserved to varying degrees in all
      previously sequenced primate herpesviruses. HHV-6B homologs were identified for
      the HSV-1 ICP18.5, ICP8, UL52, UL24, UL25 and major capsid protein. Several HHV
      6B proteins had limited amino acid similarity to their positional homologs in
      other herpesviruses. Each gene identified is highly homologous to its HHV-6A
      counterpart, including two unique HHV-6 genes predicted to encode membrane
      associated glycoproteins. However, two regions of substantial divergence were
      noted, one spanning the origin of replication and the other encoding one of the
      putative HHV-6-specific glycoprotein genes. Substitutions in the latter region
      lead to predicted differences in reading frames and protein lengths among HHV-6
      isolates.

PMID- 9155877
TI  - Alteration in the expression of endothelial cell integrin receptors alpha 5 beta
      1 and alpha 2 beta 1 and alpha 6 beta 1 after in vitro infection with a clinical
      isolate of human cytomegalovirus.
AB  - Human cytomegalovirus infection of human umbilical vein endothelial cells reduces
      the ability of these cells to bind to fibronectin, collagen type IV and laminin.
      This suppression requires active virus, since UV-inactivated virus did not alter
      the binding ability of these cells to adhere to fibronectin, collagen type IV,
      and laminin. In an attempt to elucidate the molecular mechanism of this altered
      interaction, the surface expression of alpha 5 beta 1, alpha 2 beta 1, alpha 3
      beta 1, and alpha 6 beta 1 integrins on cytomegalovirus-infected endothelial
      cells was examined using attachment inhibition assay and flow cytometric
      analysis. The results presented here show that infection with human
      cytomegalovirus selectively alters the expression of integrin on human
      endothelial cells, with the ability to induce downregulation of alpha 5 beta 1
      and alpha 2 beta 1 (p = 0.001) and p = 0.03, respectively), while significantly
      upregulating alpha 6 beta 1 (p = 0.03), and marginally upregulating alpha 3 beta
      1 (p = 0.05).

PMID- 9155878
TI  - Host range conversion of murine leukemia virus resulting from recombination with
      endogenous virus.
AB  - Ecotropic murine leukemia viruses (MuLVs) are classified into B-N-, or NB-tropic
      MuLV by their host range determined by the Fv-1 gene product. B-tropic MuLV is
      restricted in N-type mouse cells (Fv-1 n/n) and N-tropic MuLV is restricted in B
      type mouse cells (FV-1 b/b). Although forced passages in a restrictive host grant
      a wider host range (NB-tropism), we show here a host range conversion from B to N
      tropism. The conversion was most likely a result of recombination between the
      exogenously infected B-tropic MuLV and an endogenously expressed N-tropic MuLV in
      a C57BL/6 mouse cell line, YH-7.

PMID- 9155879
TI  - An RNA-dependent-RNA-polymerase activity associated with grapevine chrome mosaic
      nepovirus infection.
AB  - A virus-induced, viral RNA-specific, RNA-dependent-RNA-polymerase activity has
      been observed in vitro associated with membrane extracts of plants of three
      different species after infection with grapevine chrome mosaic nepovirus (GCMV).
      The products of this activity are full-length, positive sense GCMV RNAs present
      in double-stranded structures. As has been demonstrated for a relative to
      nepoviruses, cowpea mosaic comovirus, this activity probably corresponds to the
      nepoviral replication complex.

PMID- 9155880
TI  - Sequence analysis of the lymphotropic Aleutian disease parvovirus ADV-SL3.
AB  - About 98% of the DNA sequence of the lymphotropic Aleutian disease parvovirus
      isolate ADV-SL3 was determined and analysed. The sequence revealed that this
      isolate was a type-1 ADV strain, supporting that the currently used typing of ADV
      viruses does not correlate with virulence or pathogenicity. ADV-SL3 had a very
      high overall homology of 99.5% to the prototype strain ADV-G at the DNA level.
      Comparative sequence analyses with various ADV isolates of known virulence did
      not reveal a consensus sequence that could obviously be responsible for the
      apparently unique biological properties of this virus strain.

PMID- 9155881
TI  - Deletion analysis of a translational enhancer upstream from the coat protein open
      reading frame of potato virus S.
AB  - We have previously demonstrated that the 101 nucleotides upstream from the ATG of
      the potato virus S (PVS) coat protein gene has the ability to act as a
      translational enhancer in vitro and in vivo when fused to a range of marker
      genes. These 101 nucleotides, which have been designated VTE (viral translational
      enhancer), contain a block of nucleotide homology that is conserved between
      members of the carlavirus group, centered around a core sequence of CCTTTAGGTT.
      When deletions were generated that lacked 47 of the 5' nucleotides, but still
      retained the conserved block, and analysed in vitro and in vivo, it was observed
      that these leaders had lost their ability to act as translational enhancers.
      These results suggest that the sequences 5' to the conserved block may be acting
      as a translational enhancer or may be important in placing the conserved block in
      optimal context. This is confirmed to some extent by hybrid arrest translation
      results in which the effects on translation of oligonucleotides, complementary to
      regions within the VTE leader, were investigated. It was observed that
      oligonucleotides complementary to the nucleotides 5' to the conserved block had a
      dramatic effect on the translational competence of transcripts derived from VTE
      luciferase constructs, decreasing levels by 53%, whereas oligonucleotides
      complementary to sequences 3' to the conserved block reduced levels of
      translation by only 15.6%.

PMID- 9155883
TI  - A CaMV 35S promoter driven cDNA clone of tobacco mosaic virus can infect host
      plant tissue despite being uninfectious when manually inoculated onto leaves.
AB  - Leading from the success of inoculating plants with viral RNA transcribed in
      vitro from full length cDNA clones, attempts have been made to build cDNA clones
      which are directly infectious by inoculation. However, we and others have found
      that viral cDNA clones driven by the CaMV 35S promoter were able to infect some
      host plants yet not others, when manually inoculated onto leaves. Alternative
      methods including microprojectile bombardment have been used to deliver an
      infectious TMV construct into plant cells resulting in the infection of all TMV
      host plants tested. Lack of infection via manual inoculation may be due to
      unsuccessful delivery of a viable construct into the plant cell nucleus.

PMID- 9155882
TI  - Growth ability of auxiliary gene mutants of human immunodeficiency virus types 1
      and 2 in unstimulated peripheral blood mononuclear cells.
AB  - Mutational studies on the Vif, Vpr, Vpu, Vpx, and Nef genes of human
      immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) were performed to evaluate
      their biological functions in natural target cells. For this purpose, replication
      properties of mutant viruses derived from HIV-1 NL strain and HIV-2 GH strain in
      unstimulated peripheral blood mononuclear cells were determined. Vif- viruses of
      both HIV-1 and HIV-2 did not grow at all in these cells. Similarly, no
      replication of HIV-2 Vpx- mutant was detected. In contrast, both of Vpr- and Nef-
      viruses of HIV-1 and HIV-2, and Vpu- virus of HIV-1 grew quite well in the cells.
      These results show, together with the data previously reported, that only Vif and
      Vpx are essential for HIV replication in primary blood cell cultures.

PMID- 9155884
TI  - Comparison of a 20 kb region of human herpesvirus 6B with other human beta
      herpesviruses reveals conserved replication genes and adjacent divergent open
      reading frames.
AB  - The sequence of a 20.15 kb region from human herpesvirus 6 variant B (HHV-6B)
      strain Z29 is described (GenBank accession number L14772). Determinations of
      protein homologies for seventeen predicted gene products revealed HHV-6B homologs
      of six proteins well-conserved both in genetic context and amino acid sequence
      throughout the alpha-, beta-, and gammaherpesvirus subfamilies. These include
      proteins involved in viral DNA replication, packaging and nucleotide metabolism,
      and conserved proteins of undefined function. The close evolutionary relationship
      of the human betaherpesviruses, HHV-6B, HHV-6A, HHV-7 and human cytomegalovirus
      (HCMV) was confirmed by identification of several protein sequences encoded only
      by these viruses, including homologs of the HCMV early phosphoprotein family and
      a series of HCMV open reading frames predicted to encode glycoprotein exons.
      Homologs of essential HSV-1 replication proteins, UL8 and UL9, were also
      identified. Downstream from the conserved replication locus, each betaherpesvirus
      contains a region of divergent, small open reading frames. The evolution of this
      region and its potential use in the development of a viral vector system are
      discussed.

PMID- 9155885
TI  - Conserved sequences in the fibers of epidemic keratoconjunctivitis associated
      human adenoviruses.
AB  - The fiber gene sequences of the human adenovirus types 19 and 37 were determined.
      The predicted polypeptides exposed a high homology. Ad8, Ad19, and Ad37 can cause
      epidemic keratoconjunctivitis (EKC), whereas Ad9 only infrequently causes acute
      follicular conjunctivitis. Comparison of the fiber knobs of Ad8, Ad9, Ad19, Ad37,
      and other previously published fiber sequences revealed that only two amino acid
      residues were conserved in the fiber knobs of Ad8, Ad19, and Ad37. Since the knob
      is responsible for interaction with the cell receptor, these two amino acid
      residues could play an important role in the pathogenicity of EKC causing
      adenoviruses.

PMID- 9155909
TI  - An epidemic of apprehension: questions about HIV/AIDS to an east African
      newspaper health advice column.
AB  - While AIDS awareness is almost universal in Uganda, cultural values discourage
      open discussion of sexual behaviour. Thus many questions remain unasked,
      especially in public. This study managed to analyse some of these queries by
      examining 1252 letters written spontaneously to a newspaper health advice column:
      of the letters, more than 325 included specific questions about HIV/AIDS. Being
      written, the questions include topics too embarrassing or stigmatized to voice in
      a spoken forum. The most common underlying emotions in the letters about HIV/AIDS
      were apprehension and anxiety. Many of the letters expressed, directly or
      indirectly, that people feel they cannot control their lives and cannot
      effectively protect themselves or their families from the threat of AIDS. Health
      education information about HIV/AIDS has been interpreted through an emotional
      filter of fear, vulnerability and distrust. Writers often turned to informal
      networks of peers, friends and relatives for confirmation of information about
      HIV/AIDS. However, this 'common knowledge' seemed frequently to serve as an
      obstacle to understanding and change rather than a source of support. People
      wrote that they feared transmission of HIV through unlikely and unavoidable daily
      activities such as eating. Fear magnified a wide range of common and persistent
      symptoms (rashes, coughs, fevers, sore throats) into the feared diagnosis of
      AIDS. Accurate information is vital and necessary, but information alone will not
      offset emotional vulnerability or anxiety. People also need to have their fears
      acknowledged and addressed in a credible way.

PMID- 9155910
TI  - Participatory evaluation of counselling, medical and social services of The AIDS
      Support Organization (TASO) in Uganda.
AB  - The AIDS Support Organization (TASO) is an indigenous non-governmental
      organization (NGO) of HIV-infected and affected people in Uganda. TASO provides
      counselling, social support, medical and nursing care for opportunistic
      infections at 7 centres affiliated to district hospitals in Uganda. Between 1993
      and 1994, the services provided by TASO were evaluated through a participatory
      approach between staff and clients. TASO counselling services helped clients and
      their families to cope with HIV and AIDS, with 90.4% of clients revealing their
      serostatus, and 57.2% reporting consistent use of condoms in the past 3 months.
      TASO was also the main source of medical care for clients with opportunistic
      infections in the last 6 months (63.8%). As a result of counselling, over half of
      the clients (56.9%) made plans for the future and 51.3% wished to make wills.
      There was a high level of acceptance of people living with HIV/AIDS (PWAs) by
      families (79%) and the community (76%). Care was provided to PWAs at home mainly
      by women (86.2%). TASO has demonstrated that individuals and their families are
      able to live positively with HIV/AIDS. Through counselling, medical care and
      material support to clients and their families, TASO has effected change in
      people's attitudes, knowledge and lifestyles. In particular, TASO has
      demonstrated a strong capacity to overcome four problems that haunt AIDS care in
      most places: (1) revealing one's HIV-serostatus to relevant others; (2) accepting
      PWAs in family and community; (3) seeking early treatment; and (4) combining
      prevention and care. In general, TASO has shown that specialized services to meet
      AIDS care needs can be added to existing health services at district levels. As a
      result of the participatory evaluation, a well-accepted monitoring system was
      established.

PMID- 9155911
TI  - Heterogeneity of home care assistance needs of people with AIDS.
AB  - A multidisciplinary home care service for people with AIDS (PWAs) was started in
      Rome in September 1990. This paper describes the features of the home care
      service offered by the Associated Health Care Workers' Co-operative (OSA), an
      example of the integration of private and state systems. We detail the types and
      numbers of visits that PWAs have needed, and we explore the possible correlation
      between demographic and clinical variables and the care required. As of September
      1994 service had been provided to 372 PWAs. During the 4-year period, 62,927 home
      care visits were made (an average of 4.3 visits/patient/week): 66% were made by
      psychologists, social workers and home helps, and 34% by health professionals.
      PWAs who, at the outset of their home care, suffered from AIDS-dementia complex
      (ADC), toxoplasmosis, wasting syndrome or cytomegalovirus retinitis required the
      highest number of visits. Psychologists, social workers and home care helps made
      more frequent visits than health professionals for all AIDS-defining conditions
      except retinitis (for which 63% of visits were for health care). Our study shows
      that careful assessment of patients receiving home care helps in planning visits
      and in organizing available resources. A controlled randomized multicentre study
      is under way with the aim of determining the effectiveness of home care in terms
      of survival, quality of life and care workload and related costs.

PMID- 9155912
TI  - Health education. Vancouver Conference Review.

PMID- 9155913
TI  - Grief. Vancouver Conference Review.

PMID- 9155915
TI  - Disclosure. Vancouver Conference Review.

PMID- 9155914
TI  - Asia. Vancouver Conference Review.

PMID- 9155916
TI  - Drug use. Vancouver Conference Review.

PMID- 9155917
TI  - Interventions--gay men. Vancouver Conference Review.

PMID- 9155919
TI  - School-based sex education. Vancouver Conference Review.

PMID- 9155920
TI  - Pregnancy and childbirth. Vancouver Conference Review.

PMID- 9155918
TI  - Adolescence. Vancouver Conference Review.

PMID- 9155922
TI  - Orphans. Vancouver Conference Review.

PMID- 9155921
TI  - Women's news. Vancouver Conference Review.

PMID- 9155923
TI  - Children. Vancouver Conference Review.

PMID- 9155924
TI  - Prisons. Vancouver Conference Review.
AB  - Interesting and innovative programmes to tackle the problems associated with
      HIV/AIDS in prison have been and are being tried throughout the world. However, a
      number of political, legal and cultural barriers exist hindering the development
      of effective prevention and care and treatment approaches.

PMID- 9155925
TI  - Volunteers. Vancouver Conference Review.

PMID- 9155926
TI  - Natural history. Vancouver Conference Review.

PMID- 9155927
TI  - Living with HIV and AIDS. Vancouver Conference Review.

PMID- 9155928
TI  - Suicidal behaviours and euthanasia. Vancouver Conference Review.

PMID- 9155930
TI  - Migration and ethnicity issues. Vancouver Conference Review.

PMID- 9155929
TI  - HIV testing. Vancouver Conference Review.

PMID- 9155931
TI  - Social-cultural aspects. Vancouver Conference Review.

PMID- 9155932
TI  - A dialogue between the sexes. Vancouver Conference Review.

PMID- 9155933
TI  - Hysterectomy: a historical perspective.
AB  - In the relatively long history of man, surgery has been a comparatively recent
      development; the abdomen was first deliberately opened to remove an ovarian cyst
      by Ephraim McDowell in Kentucky in 1809. The first abdominal hysterectomy was
      performed by Charles Clay in Manchester, England in 1843; unfortunately the
      diagnosis was wrong and the patient died in the immediate post-operative period.
      The following year, Charles Clay was almost the first to claim a surviving
      patient, however she died post-operatively and it was not until 1853 that Ellis
      Burnham from Lowell, Massachusetts achieved the first successful abdominal
      hysterectomy although again the diagnosis was wrong. Vaginal hysterectomy dates
      back to ancient times. The procedure was performed by Soranus of Ephesus 120
      years after the birth of Christ, and the many reports of its use in the middle
      ages were nearly always for the extirpation of an inverted uterus and the
      patients rarely survived. The early hysterectomies were fraught with hazard and
      the patients usually died of haemorrhage, peritonitis, and exhaustion. Early
      procedures were performed without anaesthesia with a mortality of about 70%,
      mainly due to sepsis from leaving a long ligature to encourage the drainage of
      pus. Thomas Keith from Scotland realized the danger of this practice and merely
      cauterized the cervical stump and allowed it to fall internally, thereby bringing
      the mortality down to about 8%. Hysterectomy became safer with the introduction
      of anaesthesia, antibiotics and antisepsis, blood transfusions and intravenous
      therapy. During the 1930s, Richardson introduced the total abdominal hysterectomy
      to avoid serosanguineous discharge from the cervical remnant and the risk of
      cervical carcinoma developing in the stump. Apart from this innovation, and the
      transverse incision introduced by Johanns Pfannenstiel in the 1920s, there was
      little advance in hysterectomy techniques until the advent of endoscopic surgery
      and the performance of the first laparoscopic hysterectomy by Harry Reich in
      Kingston, Pennsylvania in 1988. The refinement and increasing safety of
      laparoscopic hysterectomy suggests that it will be used increasingly in the
      future, although developments in pharmacology and photodynamic therapy and
      interventional radiology may reduce the traditional indications for the
      operation.

PMID- 9155934
TI  - Hysterectomy: social and psychosexual aspects.
AB  - Studies of the psychological and sexual outcome of hysterectomy have often
      arrived at conflicting conclusions and this has resulted in some confusion among
      health professionals as well as among women themselves. This situation should
      cause concern, since the incidence of this surgery is high in most countries of
      the western world. The confusion about outcome arises out of the methodological
      problems that plagued earlier research. Some of the more recent studies using
      prospective design, standardized measures and appropriate statistical analysis
      have not implicated hysterectomy with increased psychological or sexual
      disorders. However, both before and after hysterectomy in samples studied, the
      rate of psychological disorder was higher than would have been expected in a
      normal population, although a clearer picture has emerged from the most recent
      study. In this paper, risk factors are identified, and the need to include
      women's own evaluation of the procedure is emphasized.

PMID- 9155935
TI  - Laparoscopic anatomy and dissection of the pelvis.
AB  - All anatomically important pelvic structures lie embedded in the fatty-fibrous
      connective tissue of the retroperitoneum from which they can be freed by blunt
      dissection in the correct tissue planes. By relying on fixed laparoscopic
      landmarks, the correct surgical planes of dissection can be found, and all vital
      structures freed and identified by a systematic dissection consisting of a
      precise sequence of operative steps. Once the retroperitoneal dissection has been
      completed and all vital structures identified, most gynaecological operations can
      be carried out safely and without much difficulty laparoscopically. A non
      anatomical approach to laparoscopic pelvic surgery may be easier to learn, but it
      is neither very versatile nor very safe except in the simplest of cases.

PMID- 9155936
TI  - Indications and alternatives to hysterectomy.
AB  - Hysterectomy is the commonest major operation performed by gynaecologists and is
      the definitive cure for many of it's indications which include dysfunctional
      uterine bleeding, fibroids, utero-vaginal prolapse, endometriosis and
      adenomyosis, pelvic inflammatory disease, pelvic pain, gynaecological cancers and
      obstetric complications. It is a successful operation in terms of relieving women
      of their presenting symptoms and high levels of satisfaction are reported by
      patients. However, it has a high risk of complications, involves a prolonged
      convalescence, is expensive and to some women represents a loss of femininity. It
      should only be employed after trying conservative treatments first if
      appropriate. If this fails, currently only endometrial ablation and myomectomy
      are valid alternatives to hysterectomy. If ultimately hysterectomy is required,
      there is considerable evidence that patient care can be improved by increasing
      the proportion of operations that are done vaginally and laparoscopically and
      decreasing the number of laparotomies.

PMID- 9155938
TI  - Vaginal hysterectomy.
AB  - Hysterectomy is the most common non-pregnancy-related surgical procedure
      performed in the USA. The ratio of abdominal operations to vaginal operations is
      3:1, which probably reflects surgeon's experience and practice styles, the
      absence of clear guidelines for selecting a surgical route, lack of patient
      knowledge about the options, and inappropriate decision-making. With the trend
      toward evidence-based and outcome-based practice, the indications and
      contraindications for abdominal, vaginal, and laparoscopically-assisted
      hysterectomy must be examined critically. In the author's extensive experience
      the rates of abdominal, vaginal, and laparoscopically-assisted procedures are
      1.9, 88.7, and 9.4%, respectively. Techniques useful in vaginal hysterectomy with
      or without simultaneous oophorectomy, the pros and cons of simultaneous
      incidental appendectomy, and methods of protecting the ureter are discussed.

PMID- 9155937
TI  - Total abdominal hysterectomy.
AB  - Total abdominal hysterectomy will be performed on one of every three women in the
      USA. While few changes have occurred in modern times, operative laparoscopy is
      being used for hysterectomy, though its true role remains unclear. This chapter
      reviews the indications, preparation and common complications related to total
      abdominal hysterectomy. A detailed description of abdominal hysterectomy as it is
      performed at the Mayo Clinic is presented. Key features are pointed out, and the
      need for proper surgical technique is stressed; specifically, the proper
      dissection of ureter, bladder and rectum are reviewed and emphasis placed on the
      need for every pelvic surgeon to possess the skills required for performing
      these.

PMID- 9155939
TI  - Laparoscopic hysterectomy.
AB  - The terminology of laparoscopically-assisted hysterectomies needs to be
      simplified and clarified. Laparoscopic hysterectomy should be used as a general
      term, whereas operative laparoscopy before hysterectomy, laparovaginal,
      laparoscopic total and subtotal hysterectomy should be used to describe the types
      of laparoscopic hysterectomy. The complication rates from laparoscopic
      hysterectomy, abdominal hysterectomy and vaginal hysterectomy are similar. The
      lower febrile morbidity after laparoscopic hysterectomy may be due to improved
      pelvic visualization compared to vaginal and abdominal hysterectomy. Controlled
      trials show that laparoscopic hysterectomy has advantages over abdominal
      hysterectomy which include reduced pain, reduced hospitalization time and earlier
      return to work. Most abdominal hysterectomies can be replaced by laparoscopic or
      vaginal hysterectomies. Whether this happens will depend upon adequate training
      facilities.

PMID- 9155940
TI  - Comparison of hysterectomy techniques and cost-benefit analysis.
AB  - There are an increasing number of approaches to the surgical removal of the
      uterus; each of these has clinical advantages and disadvantages. This paper
      outlines the various forms of laparoscopic hysterectomy currently undertaken and
      attempts to compare outcome measures and complications with these new approaches.
      In general laparoscopically-assisted vaginal hysterectomy appears to be
      associated with longer operating time but less post-operative pain and a shorter
      convalescent period than both abdominal and vaginal hysterectomy. Economic
      evaluation is dependent on local factors and upon the type of technique adopted.
      The use of disposable instrumentation profoundly influences the costs.
      Laparoscopically-assisted vaginal hysterectomy can be performed for similar or
      less total costs than conventional surgery providing techniques using re-usable
      equipment are employed. The place of the laparoscope in facilitating hysterectomy
      is not yet defined. Techniques are continuing to evolve. The debate now appears
      to be how laparoscopic and vaginal surgical skills can be best combined to ensure
      the best possible patient outcome.

PMID- 9155942
TI  - Laparoscopic supracervical hysterectomy.
AB  - Supracervical hysterectomy is a viable alternative for those individuals
      requiring uterine extirpation without indications for cervical removal. The
      laparoscopic approach to this procedure provides even lower morbidity and
      therefore can enhance clinical outcomes. The procedure is versatile in that most
      patients are amenable pathologically to this approach, particularly those
      individuals with large lieomyomata. Five year follow-up data is presented on 236
      cases performed by the author including clinical outcomes and morbidity
      information. The procedure as performed by the author is presented in detail with
      illustrations of critical aspects of the technique of LSH.

PMID- 9155941
TI  - Radical hysterectomy.
AB  - Radical hysterectomy for the treatment of cervical cancer was first performed
      just over 100 years ago. Refinements of surgical technique and improvements in
      supportive measures, such as transfusions and antibiotics, have brought about a
      marked decrease in morbidity and mortality from surgery and improvement in
      overall survival. The indications for operation, pre-operative investigations and
      preparation, surgical technique, post-operative complications and their
      management, and factors influencing prognosis are discussed.

PMID- 9155943
TI  - Complications of hysterectomy.
AB  - The complications of hysterectomy are discussed, generally speaking their
      definition is poorly standardized and direct comparisons are extremely difficult.
      Furthermore, there is uncertainty as to what is meant by laparoscopic
      hysterectomy. The complications are discussed as post-operative fever,
      haemorrhage, injury to adjacent organs, other complications and life-threatening
      events. The incidence of post-operative infection and haemorrhage is least with
      the laparoscopic approach, but injury to surrounding organs is probably greater.
      In 1982, the Collaborative Review of Sterilization study data suggested an
      average woman of reproductive age with no pre-existing medical condition, no
      previous abdominal surgery, and who received prophylactic antibiotics, was best
      served by vaginal hysterectomy without colpororrhaphy rather than an abdominal
      procedure. This does not seem to have changed. The incidence of abdominal
      hysterectomy may be reduced by adding laparoscopy to vaginal hysterectomy to deal
      with adhesive disease, endometriosis or adnexal disease. Laparoscopic
      hysterectomy is feasible and safe but the indications for this approach have not
      yet been established.

PMID- 9155944
TI  - Cutaneous tuberculosis in Blackburn district (U.K.): a 15-year prospective
      series, 1981-95.
AB  - Data collected prospectively on all 1065 cases of tuberculosis occurring in the
      Blackburn district, U.K. (population 265,000), over a 15-year period have been
      analysed, and from these 47 cases of cutaneous tuberculosis have been identified.
      The most common form was scrofuloderma, skin involvement with adjacent structural
      disease, of which there were 26 cases (55.3%). There was no ethnic bias in this
      group. The eight white patients with scrofuloderma were of average age 66 years,
      and are thought to represent reactivation disease. Six patients (12.8%) had lupus
      vulgaris, four (8.5%) had metastatic tuberculosis and 10 (21.3%) were diagnosed
      as having one of the tuberculides, of which Bazin's disease (erythema induratum)
      was the most common. In addition, one patient (2.2%) had orificial tuberculosis.
      In contrast to scrofuloderma, all other forms of cutaneous tuberculosis occurred
      almost exclusively in patients from the Indian Subcontinent (ISC). The high
      incidence of tuberculosis in Blackburn is mainly linked to its significant
      proportion of residents of ISC ethnic origin. There were no cases of HIV
      infection coexisting with either cutaneous or other forms of tuberculosis.
      Recommendations for the treatment of cutaneous tuberculosis are made.

PMID- 9155945
TI  - Non-dermatophytes in onychomycosis of the toenails.
AB  - A multicentre trial for the treatment of dermatophyte onychomycosis of the
      toenails with terbinafine was carried out in Australia and New Zealand. Between
      eight and 12 nail samples were obtained from each of the 118 patients in the 48
      week trial, and each sample was investigated by direct microscopy and culture for
      dermatophyte and non-dermatophyte fungi. Patients were randomized to treatment
      with terbinafine at 250 mg/day or placebo for the first 12 weeks of the study,
      then non-responders were offered a 12-week course of terbinafine from week 28.
      All patients had a dermatophyte infection. In 42 patients (36%) microscopy and
      mycological culture identified dermatophytes alone. In the remaining 76 patients
      (64%), a non-dermatophyte mould or yeast was also isolated at some stage during
      the trial, but in only three patients did the same non-dermatophyte persist in
      two or more successive nail specimens. The presence of a fungal contaminant in
      addition to a dermatophyte had no apparent effect on the efficacy of treatment
      with terbinafine. We conclude that non-dermatophyte moulds and yeasts are
      generally found as contaminating organisms in dermatophyte onychomycosis,
      secondary to the dermatophytes, and that they do not influence the outcome of
      treatment.

PMID- 9155946
TI  - A possible explanation for the increased referral of atopic dermatitis from the
      Asian community in Leicester.
AB  - The population of the city of Leicester contains, in addition to the 'native'
      population, a large immigrant 'Asian' community originating from the Indian
      subcontinent. Among referrals to our department, atopic dermatitis (AD) was 3,3
      times more common in Asians. We therefore performed a study based on a cohort of
      consecutive births in Leicester hospitals to investigate the possible ethnic
      difference in prevalence and to examine possible reasons for an ethnic difference
      in referral pattern. Parents of 1,800 children were asked at the time of the
      birth to allow their child to be entered on a register. A year later, parents of
      a sample of 499 of these children, 158 Asian and 341 non-Asian, were invited for
      interview and for examination of the children. A total of 413 children were
      examined. The overall point prevalence of AD was 10.7% (95% confidence interval,
      7.7%-13.7%). There was no significant ethnic difference. However, a history of
      eczema in a first degree relative was found in 14.2% of Asian subjects and 35.1%
      of non-Asians (P < 0.0001, chi-square test). The data suggest the increased
      referrals to our clinic from the Asian community may result from a lower level of
      familiarity with AD.

PMID- 9155947
TI  - Predictors of atopic dermatitis in Leicester children.
AB  - There is little contemporary data available on the prevalence of atopic
      dermatitis (AD) or the risk factors associated with this disease. We therefore
      performed a prospective study of 1-year-old children based on a cohort of
      consecutive births in Leicester hospitals. Parents of 1800 children born between
      March and May 1992 were asked at the time of the birth to allow their child to be
      entered on a register. A sample of 499 of these children were invited for
      interview and examination at 1 year of age. Data were collected on gestational
      maturity, birth weight, feeding pattern, family history of eczema and atopy,
      social class and other parameters. Four hundred and thirteen of the 499 children
      were examined (83%). The overall point prevalence of AD was 10.7% (95% confidence
      interval, 7.7%-13.7%). The most significant risk factor for a child developing AD
      was a parental history of eczema.

PMID- 9155948
TI  - Measurement of quality of life in atopic dermatitis: correlation and validation
      of two different methods.
AB  - Atopic dermatitis is a chronic relapsing condition that can have considerable
      effects on the lives of sufferers. It is apparent that good, valid measures of
      life quality are necessary for quantifying the patients' perspective of the
      severity of their disease and the Dermatology Life Quality Index is often
      employed in clinical research. In a community study of atopic dermatitis we have
      assessed disability using the Dermatology Life Quality Index and the Patient
      Generated Index and compared the results from both indices. The results were
      significantly correlated and reflected the range of disability in patients in the
      community. Some items of the Dermatology Life Quality Index were not relevant for
      atopic dermatitis patients in the community and others, including swimming and
      sleep loss, were often cited in the Patient Generated Index but are not included
      in the Dermatology Life Quality Index. The Patient Generated Index is a novel,
      flexible approach to quality of life measurement that may be suitable for
      reflecting the wide variety of disability that is experienced by dermatological
      patients.

PMID- 9155949
TI  - The basement membrane zone in lichen sclerosus: an immunohistochemical study.
AB  - The alteration in expression of basement membrane zone (BMZ) components in lichen
      sclerosus was investigated by immunohistochemical staining of skin biopsies from
      seven patients with histologically confirmed disease compared with controls.
      Monoclonal antibodies and polyclonal sera directed against proteins of the
      hemidesmosomes, anchoring fibrils, lamina lucida, lamina densa and BMZ collagens
      were used. Characteristic histological appearances at the dermo-epidermal
      junction were reflected in widespread alterations in antigen expression in the
      epidermal basement membrane and the papillary dermis. Expression of the proteins
      which constitute the structural scaffold (collagen IV and VII) were increased in
      lichen sclerosus. Expression of hemidesmosomal proteins which mediate adhesion
      and cell to matrix interaction (alpha 6 beta 4 and bullous pemphigoid antigen)
      and expression of anchoring filament components were markedly reduced, suggesting
      that the epidermal cells are exposed to selective damage.

PMID- 9155950
TI  - A prospective study of Mohs' micrographic surgery in two English centres.
AB  - In this study we report the results of using Mohs' micrographic surgery (MMS) to
      treat 228 basal cell carcinomas (BCCs) in both a teaching and a district general
      hospital. The criteria for case selection and the 5-year recurrence rate of 3.8%
      are comparable with figures from the U.S.A. Our experience shows that high cure
      rates in difficult and, especially, recurrent tumours are obtainable using MMS in
      both a teaching and a district general hospital setting. Such treatment should be
      more widely available in the U.K. particularly as the incidence of BCCs is
      rising.

PMID- 9155951
TI  - Cyclosporin inhibits intercellular adhesion molecule-1 expression and reduces
      mast cell numbers in the asebia mouse model of chronic skin inflammation.
AB  - The asebia mouse represents a spontaneous mutation in BALB/c mice leading to
      hyperplasia of the epidermis and chronic inflammatory dermal changes including
      enhanced cellularity, oedema and elevated mast cell numbers. We demonstrated that
      asebia mice have constitutively elevated intercellular adhesion molecule-1 (ICAM
      1) mRNA expression, which is not detectable in the wild type, and that dermal
      mast cell numbers were 3.1-fold higher than the wild type (P < 0.001). We
      utilized this model to explore the anti-inflammatory effects of cyclosporin A
      (CsA). After 3 weeks subcutaneous injection with 5 or 10 mg/kg CsA the expression
      of ICAM-1 mRNA was determined by semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR) and was found to be decreased 2.7-fold (P <
      0.001) and three-fold (P < 0.001) relative to controls for 5 and 10 mg/kg
      treatments, respectively. Dermal mast cell counts were dose-dependently decreased
      by CsA. Mast cells, visualized by toluidine blue staining, decreased 4.5-fold
      with 10 mg/kg CsA (P < 0.001) bringing them down to numbers typical of the wild
      type. CsA also appeared to stabilize mast cell histamine content. Histological
      examination of haematoxylin-eosin-stained sections revealed that CsA treatment
      restored the wild-type skin phenotype decreasing epidermal hyperplasia, dermal
      cellularity and oedema. Thus, CsA exhibits a wide range of anti-inflammatory
      effects including reduction of ICAM-1 expression and mast cell numbers, and may
      be useful in the treatment of mast cell-mediated dermatoses.

PMID- 9155952
TI  - Treatment of psoriasis with intermittent short course cyclosporin (Neoral). A
      multicentre study.
AB  - A 1 year, prospective multicentre study was performed to investigate the efficacy
      and safety of intermittent treatment with cyclosporin in psoriasis vulgaris.
      Subjects received cyclosporin (Neoral) 5 mg/kg per day until achieving 90%
      reduction in area affected, or for a maximum of 12 weeks. Those failing to
      demonstrate a satisfactory response were withdrawn. When further treatment was
      required, cyclosporin was recommenced. This cycle was repeated up to three times.
      Psoriasis activity was recorded using the area affected and sign scores for
      erythema, scaling and infiltration. Overall assessments of response and
      tolerability were recorded. Forty-one subjects, mean age 36, mean PASI 12.8,
      entered the first treatment period. Thirty-three received a second period of
      treatment and 16 a third. Eighteen failed to complete the study as planned: five
      were withdrawn due to adverse events, four due to treatment failure and nine due
      to protocol violations. At the end of each treatment period, significant
      improvements were seen in all efficacy parameters. Overall response was graded as
      'considerable improvement' or 'minimal or no symptoms', by over 80% of subjects
      and investigators. Median intervals to relapse for subjects remaining in the
      study were 72 days (range 28-329) and 53 days (range 14-141) after periods 1 and
      2, respectively. There were significant increases in mean serum creatinine and
      blood pressure during each treatment period. However, there were no significant
      differences in either parameter between baseline and the final follow-up visit.
      At the end of each treatment period, overall tolerability of the treatment was
      considered 'good' or 'very good' by over 80% of subjects and investigators.

PMID- 9155953
TI  - Renal biopsy findings in long-term cyclosporin treatment of psoriasis.
AB  - Renal biopsies were performed in 30 psoriatics during long-term low-dose
      cyclosporin (CsA) therapy (range 2.5-6 mg/kg per day) of from 6 months to 8
      years. The study included pretreatment biopsies in 25 of the patients. After 2
      years all biopsies shared features consistent with CsA nephropathy despite
      completely normal pretreatment morphology in 17 of the 25 patients. The severity
      of the findings which consisted of arteriolar hyalinosis, focal interstitial
      fibrosis and sclerotic glomeruli increased with length of therapy. Mild renal
      lesions were seen during the first 2 years. After 4 years all but one had
      arteriolar hyalinosis, with interstitial fibrosis pronounced in five and moderate
      in six of 11 patients. At the same time glomerular sclerosis had become
      significant. A decrease in glomerular filtration rate (GFR) correlated with
      severity of structural lesions. The data from our study together with experiences
      from cardiac-transplanted patients treated with CsA indicate that patients with
      psoriasis after 2 years therapy with CsA should be rotated to other treatments or
      be followed carefully by GFR and sequential renal biopsies.

PMID- 9155954
TI  - Effect of calcitriol on the production of T-cell-derived cytokines in psoriasis.
AB  - Although the use of vitamin D analogues in the treatment of psoriasis has been an
      important new development, the mechanisms of action of these drugs are not fully
      understood. Psoriasis results from hyperproliferation of keratinocytes, and
      various studies attribute a crucial role to the locally infiltrating T
      lymphocytes. In an attempt to add to the understanding of the mechanisms of
      calcitriol therapy, we determined the effect of this drug on T cells by studying
      its effect on proliferation and on the production of various cytokines by T-cell
      clones prepared from psoriatic skin after non-specific activation with the
      combination of phytohaemagglutinin (PHA) and phorbol myristate acetate (PMA). The
      addition of increasing doses (10(-9)-10(-5) mol/l) of calcitriol to these T cells
      resulted in a dose-dependent inhibition in lymphocyte proliferation and in
      production of the type 1 cytokines IFN-gamma and IL-2, the type 2 cytokines IL-4
      and IL-5. The general cytokines TNF-alpha and GM-CSF were not significantly
      inhibited. These data suggest that calcitriol is involved in the treatment of
      psoriasis via inhibition of the expansion, and cytokine production, of skin
      infiltrating T lymphocytes.

PMID- 9155955
TI  - Anthralin (dithranol) in vitro inhibits human monocytes to secrete IL-6, IL-8 and
      TNF-alpha, but not IL-1.
AB  - Anthralin is a most widely used compound for topical treatment of psoriasis.
      Whereas numerous studies have ascertained anthralin as a safe and effective drug
      its mode of action still remains unclear. Previous studies demonstrated dose
      dependent inhibition of a number of pro-inflammatory functions in human
      neutrophils and monocytes (MO). The aim of the present study was to investigate
      in stimulated MO the effect of anthralin on the secretion of cytokines which are
      of known importance for the psoriatic tissue reaction. Highly purified MO were
      incubated with anthralin (0.01-1.0 microgram/ml), its clinically inactive
      derivative danthrone (0.1 and 10 micrograms/ml), the solvent acetone, or medium
      alone. Culture supernatants were analysed for immunoreactivity for interleukin-1
      beta, and -8 (IL-1 beta, IL-8), and tumour necrosis factor alpha (TNF-alpha) by
      specific ELISA. IL-6 bioactivity was determined using the B9-bioassay.
      Additionally, IL-1 bioactivity was measured by the D10[N4]M-bioassay. The results
      show a dose-dependent inhibition of MO IL-6, IL-8, and TNF-alpha release with a
      half-maximal inhibitory concentration of 0.25-0.6 microgram/ml of anthralin.
      There was no effect of danthrone or acetone on the secretion of these cytokines
      from MO. Secretion of IL-1 beta immunoreactivity measured by ELISA as well as
      determination of biological activity of IL-1 using the D10[N4]M-bioassay revealed
      a slight increase in IL-1 secretion with a maximum at an anthralin concentration
      of 0.1 microgram/ml. Danthrone at a concentration of 10 micrograms/ml and acetone
      (0.1%) similarly enhanced IL-1 secretion from human MO measured by both methods.
      Our results demonstrate a differential, dose-dependent inhibition of cytokine
      secretion from human MO by anthralin. The present data provide evidence that the
      anti-inflammatory and anti-proliferative activity of anthralin may at least in
      part be due to its inhibitory effect on pro-inflammatory cytokine secretion by
      MO.

PMID- 9155956
TI  - Double-blind trial of botulinum A toxin for the treatment of focal hyperhidrosis
      of the palms.
AB  - We performed a randomized double-blind study within-group comparison in 11
      patients to study the effect of subcutaneous injections of botulinum A toxin in
      focal hyperhidrosis of the palms. A total dose of 120 mU (mouse units) of
      botulinum A toxin (Dysport) was injected into six different sites on one palm,
      whereas the other was injected with sterile saline. Objective quantification of
      sweat production was performed using digitized ninhydrin-stained sheets. Three
      weeks after treatment, the mean reduction of sweat production in the botulinum A
      toxin-treated palms was 26% (P < 0.001), after 8 weeks 26% (P = 0.002) and after
      13 weeks 31% (P < 0.001). Subjective assessment of sweat production by the
      patients using a visual analogue scale showed a 38% improvement in the botulinum
      A toxin-treated palms at 3 weeks (P = 0.002), 40% at 8 weeks (P = 0.002) and 38%
      at 13 weeks (P = 0.002). Neither the objective measurement nor the subjective
      rating showed a statistically significant reduction of sweating in the placebo
      treated palms. Three patients reported reversible minor weakness of powerful
      handgrip after injection at the toxin-treated site, lasting between 2 and 5
      weeks.

PMID- 9155958
TI  - The prevalence of epidermolysis bullosa in Scotland.
AB  - The prevalence of epidermolysis bullosa (EB) in Britain and most other countries
      is unknown. Patients suffering from the inherited forms of EB and living in
      Scotland have been traced. Two hundred and fifty-nine affected people from 76
      families have been identified, of whom 211 were clinically assessed. One-third of
      these Scottish EB sufferers had never been seen by a dermatologist. In Lothian,
      where there appears to be a relatively high prevalence of EB, 75% of patients
      were unknown to their general practitioners. The point prevalence of all forms of
      EB at the outset of the study was 49.0 per million, comprising EB simplex 28.6
      per million and dystrophic EB 20.4 per million. Extrapolation of accurate data
      available for the Lothians suggests that the point prevalence of all forms of EB
      in Scotland is in excess of these figures.

PMID- 9155957
TI  - Persistent pruritus after hydroxyethyl starch infusion therapy: a result of long
      term storage in cutaneous nerves.
AB  - A high incidence of severe pruritus has been observed after the administration of
      hydroxyethyl starch (HES) on account of plasma volume substitution and
      improvement of the microcirculation. The aim of this study was to elucidate the
      possible pathomechanisms of HES-induced itching. Skin biopsies were taken from 93
      patients, half of them presenting with pruritus, who received HES of various
      preparations and cumulative dosages. The samples were subjected to immunoelectron
      microscopical investigation using an antibody highly specific for HES. After
      infusion therapy with HES, formation of intracytoplasmic storage vacuoles in the
      skin could be demonstrated in all patients. A dose-dependent uptake of HES was
      first detectable in macrophages and, thereafter, in endothelial and epithelial
      cells. Consecutive control biopsies taken from single patients revealed a
      subsequent reduction of the vacuoles, in size and number, within 3 years, thus
      indicating a regular cutaneous metabolism of HES. Patients suffering from
      pruritus consistently showed additional deposition of HES in small peripheral
      nerves. HES-reactive vacuoles could be demonstrated in the Schwann cells of
      unmyelinated, as well as small myelinated, nerve fibres, and in endoneural and
      perineural cells. Neural devacuolization paralleled the clinical improvement in
      the symptoms. In conclusion, HES deposits in cutaneous nerves, as a consequence
      of a higher cumulative dosage, may account for the itching seen after HES
      infusion.

PMID- 9155959
TI  - Site, histological type, and thickness of primary cutaneous malignant melanoma in
      western Netherlands since 1980.
AB  - An increasing incidence of cutaneous malignant melanoma had been observed in the
      Netherlands. Therefore, between 1989 and 1992 a preventive skin cancer campaign
      was organized in part of western Netherlands. The effect of this screening
      campaign has yet to be evaluated by investigating the distribution of all in situ
      and invasive primary cutaneous melanoma according to anatomical subsite, tumour
      thickness, and histological type in a population-based study during 1980-92. A
      total number of 2236 (1361 female; 875 male) invasive and 580 (395 female; 185
      male) in situ melanomas were diagnosed. The median age of patients with thin
      lesions was 46 years, intermediate lesions 54 years, and thick lesions 65 years,
      which may be indicative of slow tumour progression. The median thickness of the
      invasive lesions was 0.9 mm for women and 1.1 mm for men and the invasive to in
      situ ratio was 3.4 for female and 4.7 for male subjects, suggesting a reasonable
      awareness of melanoma in this population. The relative tumour density (RTD) was
      remarkably high for melanomas in the head/neck area for both sexes and invasive
      melanoma on the male trunk and the lower legs of females. The low RTD of invasive
      melanomas on the lower limbs of men and the high density in the head/neck area
      for both sexes are remarkable and support the aetiological role of ultraviolet
      exposure. It is concluded that our findings are in many ways similar to those of
      other descriptive studies.

PMID- 9155960
TI  - Expression of endothelial nitric oxide synthase in human eccrine clear cells.
AB  - Nitric oxide is generated from L-arginine by nitric oxide synthase (NOS), which
      has at least three isoforms; endothelial-type NOS (eNOS) and brain-type NOS
      (bNOS) are constitutive enzymes, and inducible-type NOS (iNOS) is expressed after
      stimulation. Studies by the avidin-biotin immunocomplex method, revealed eNOS
      immunoreactivity exclusively in the human eccrine clear cells. No eNOS
      immunoreactivity was observed in the eccrine dark cells or myoepithelial cells.
      No staining of iNOS or bNOS was observed in the eccrine gland. These findings
      indicate that NO plays a physiological part in the production and/or excretion of
      sweat in the human skin eccrine gland.

PMID- 9155961
TI  - A multicentre (double-blind) comparative study to assess the safety and efficacy
      of fluconazole and griseofulvin in the treatment of tinea corporis and tinea
      cruris.
AB  - In a double-blind, parallel group study we compared fluconazole 150 mg once
      weekly with griseofulvin 500 mg once daily for 4-6 weeks in the treatment of
      tinea corporis or tinea cruris. Eighty-four of 114 patients (74%) (39% after 3
      weeks) were clinically cured in the fluconazole group compared with 72 of 116
      (62%) (39% after 3 weeks) in the griseofulvin group (P = 0.06). In the
      fluconazole group 78% were mycological cured compared with 80% in the
      griseofulvin group. In the fluconazole group nine patients (7.5%) had treatment
      related adverse events and in the griseofulvin group 15 patients (12.5%) had
      adverse events. Fluconazole 150 mg once weekly for 6 weeks is both clinically and
      mycologically effective in the treatment of tinea corporis and tinea cruris and
      few side-effects were reported.

PMID- 9155962
TI  - Carney complex: report of a kindred with predominantly cutaneous manifestations.
AB  - We report a four-generation kindred with the complex of myxomas, spotty
      pigmentation and endocrine overactivity. This kindred demonstrates a relatively
      limited phenotypic expression with predominance of cutaneous features. Male-to
      male transmission confirms the autosomal dominant nature of the condition. We
      propose that pilonidal sinus may be an associated manifestation in this kindred.

PMID- 9155965
TI  - Reversible dilated cardiomyopathy following treatment of atopic eczema with
      Chinese herbal medicine.
AB  - Chinese herbal medicines are increasingly being used as an alternative treatment
      for chronic skin disease. Most patients and many doctors remain insufficiently
      aware of their potential toxicity. We report a patient with eczema who developed
      a severe cardiomyopathy following a 2-week course of Chinese herbal medicine. The
      connection between the two conditions was not made until 2 weeks after
      presentation when the patient was specifically asked if she had ingested any
      unusual substances. The belief that herbs, as natural products available without
      prescription, are harmless, is commonplace and patients may not consider them
      worthy of mention during a standard medical history.

PMID- 9155964
TI  - A novel human papillomavirus identified in epidermodysplasia verruciformis.
AB  - Epidermodysplasia verruciformis (EV) is a rare inherited condition in which there
      is widespread infection with human papillomavirus (HPV). Patients have a high
      risk of developing squamous cell carcinoma and Bowen's disease on sun-exposed
      sites. We describe a Jamaican man with the typical clinical and histopathological
      features of EV.HPV 8, 24 and a subtype of HPV 38, along with a novel HPV sequence
      most closely related to HPV 9 have been detected in his skin lesions. Although
      skin tumours are rare in black patients with EV and he has lived in a temperate
      climate most of his life, several of the lesions showed bowenoid atypia and he is
      at risk of developing invasive cutaneous malignancies.

PMID- 9155963
TI  - Michelin tire syndrome: a congenital disorder of elastic fibre formation?
AB  - We describe a 15-month-old girl with Michelin tyre syndrome. She had hirsuties
      and marked skin folds. Histological examination showed fragmented elastic fibres
      in addition to smooth muscle hamartoma. On electron microscopy, decreased
      deposition of elastin was observed. We speculate that elastic fibre abnormalities
      may account for the characteristic skin changes in the Michelin tyre syndrome.

PMID- 9155966
TI  - Cutaneous manifestations of fucosidosis.
AB  - Angiokeratoma corporis diffusum (ACD) is still often thought to be synonymous
      with Anderson-Fabry disease, a deficiency of alpha-galactosidase. It is
      important, however, to consider other possible enzyme deficiencies in patients
      with ACD. We report an 8-year-old boy with neurodevelopmental delay who was
      diagnosed as having fucosidosis following recognition of ACD in the dermatology
      department. Other cutaneous features in this patient included distal transverse
      purple nail bands, acrocyanosis and a naevus anaemicus. Histology and electron
      microscopy of skin papules was consistent with angiokeratoma. Skeletal survey
      demonstrated dysostosis multiplex. The diagnosis was confirmed by leucocyte
      oligosaccharide enzyme analysis. There are only three previous reports of
      fucosidosis in the U.K.

PMID- 9155967
TI  - Unique digital skin lesions associated with systemic sclerosis.
AB  - A 40-year-old woman with systemic sclerosis presented with multiple, large soft
      skin lesions with a cystic appearance over the interphalangeal joints of both
      hands. Aspiration of one of these lesions revealed the presence of a yellowish
      mucoid material which rapidly reappeared. Surgical dissection and excision of the
      masses was followed by recurrence a few months later. Pre-operative diagnosis was
      that of myxoid cysts, but the histological picture was reminiscent of cutaneous
      focal mucinosis, another form of primary mucinosis. The origin of these unique
      skin lesions is unclear, but speculation on a possible aetiological relationship
      between them and systemic sclerosis is presented.

PMID- 9155968
TI  - Xanthomas due to generalized oedema.
AB  - A unique case of normolipaemic eruptive xanthomas due to generalized oedema is
      described. We propose that in this patient eruptive xanthomas were caused by the
      capillary leak syndrome. The increased vascular permeability could be responsible
      for leakage of lipoproteins into the dermis with subsequent phagocytosis by
      histiocytic cells.

PMID- 9155969
TI  - Epidermolysis bullosa acquisita associated with epidermal-binding circulating
      antibodies.
AB  - Epidermolysis bullosa acquisita (EBA) is a rare, immunobullous disease,
      characterized by circulating and tissue-bound antibodies against type VII
      collagen (C7) of anchoring fibrils in the cutaneous basement membrane zone. These
      antibodies localize to the dermal aspect of salt-split skin on indirect and
      direct immunofluorescence (IMF). We report two patients with clinical features of
      EBA, in whom circulating IgG antibodies bound to the epidermal aspect of salt
      split skin. In both patients direct IMF of salt-split perilesional skin revealed
      dermal IgG deposits, and direct immunogold immunoelectron microscopy showed
      antibody deposits in the region of anchoring fibrils. Their serum failed to react
      with epidermal or dermal extracts on Western immunoblotting. Epidermal-binding
      antibodies have not been reported previously in association with EBA, and the IMF
      findings in these cases suggest the development of autoantibodies to additional
      epidermal-associated antigens. Target antigen heterogeneity has been reported in
      most other immunobullous diseases, and may be a hitherto unrecognized feature of
      EBA.

PMID- 9155970
TI  - Kikuchi disease (histiocytic necrotizing lymphadenitis) in association with
      HTLV1.
AB  - We report a 25-year-old male with fever, generalized lymphadenopathy and an
      erythematosus maculo-papular eruption affecting face and upper body. A diagnosis
      of Kikuchi disease (necrotizing histiocytic lymphadenitis) was made on lymph node
      histology. The patient was found to be positive for the human T-cell leukaemia
      lymphoma virus (HTLV1). Kikuchi disease has been reported in association with
      infections such as Epstein-Barr virus (EBV), herpes (HHV6) and toxoplasmosis, but
      to our knowledge this is the first case of Kikuchi disease associated with HTLV1.

PMID- 9155971
TI  - Expression of adhesion molecules in pagetoid reticulosis (Woringer-Kolopp
      disease).
AB  - Cell adhesion molecules play a critical role in lymphocyte migration and homing.
      They convey tissue-specific homing properties to lymphocyte subsets and regulate
      the positioning of these subsets in the body. In a patient with pagetoid
      reticulosis, a rare form of cutaneous T-cell lymphoma characterized by extreme
      epitheliotropism, we examined the expression of adhesion molecules. The
      neoplastic T lymphocytes showed a strong expression of cutaneous lymphocyte
      antigen, a skin-homing receptor which interacts with E-selectin on skin
      endothelium. alpha E beta 7 an adhesion molecule interacting with E-cadherin on
      epithelial cells, was also expressed on tumour cells. These findings suggest that
      adhesion molecules are responsible for the unique growth pattern in pagetoid
      reticulosis, and for the clinical behaviour of the disorder.

PMID- 9155972
TI  - Mycosis fungoides palmaris et plantaris: successful treatment with the carbon
      dioxide laser.
AB  - Mycosis fungoides palmaris et plantaris (MFPP) is an uncommon form of mycosis
      fungoides with main involvement on palms and soles. The lesions may be quite
      hyperkeratotic. A 56-year-old patient with MFPP was successfully treated with the
      carbon dioxide (CO2) laser. There was no recurrence of disease at treated sites
      and excellent cosmetic results were obtained. Treatment with the CO2 laser may be
      considered a therapeutic option.

PMID- 9155973
TI  - Werner's syndrome--chromosome analyses of cultured fibroblasts and mitogen
      stimulated lymphocytes.
AB  - Two cases of Werner's syndrome are reported. Fibroblasts derived from both
      patients revealed reduced population doubling numbers. Chromosomal analyses for
      fibroblasts from both patients and lymphocytes from one patient revealed that
      chromosomal aberrations occur frequently and randomly. Although some of the
      chromosomal aberrations involved sites where tumour suppressor genes have been
      mapped, neither of our patients demonstrated malignancy. Chromosomal aberration
      at one critical site may not be sufficient to induce cancer or additional factors
      may be necessary.

PMID- 9155974
TI  - Erythema elevatum diutinum in association with coeliac disease.
AB  - Erythema elevatum diutinum (EED) has been described in association with several
      immunological or infectious diseases. We describe a female patient who presented
      with clinically and histologically typical EED in whom previously undiagnosed
      coeliac disease was found. Appearance of EED lesions was preceded by widespread
      joint pains. In extensive laboratory tests, the only abnormal findings were an
      elevated erythrocyte sedimentation rate (ESR) and decreased haemoglobin and folic
      acid levels. Later, IgA and IgG type antireticulin and antigliadin antibodies
      were detected. Serum total IgA was elevated but no paraproteinaemia was found. In
      lesional skin, granular deposits of IgA and C3 were seen at the dermo-epidermal
      junction. A duodenal biopsy revealed total villous atrophy. Dapsone treatment was
      partly effective but complete healing of the EED lesions was achieved only after
      the introduction of a strict gluten-free diet. The patient has now remained
      symptom-free on the diet for 1.5 years.

PMID- 9155975
TI  - Painful piezogenic pedal papules: response to local electro-acupuncture.
AB  - We report the case of a woman who had pain in both heels which was exacerbated by
      long periods of exercise. On examination, there were small flesh-coloured papules
      which appeared over the medial and lateral aspects of the heels only on weight
      bearing. Coincidentally, she was noted to have larger flesh-coloured papules over
      the anterior surface of the shins. The diagnoses of painful piezogenic pedal
      papules and bilateral tibialis anterior muscle herniation, respectively, were
      made. After many attempts to control the pain, a course of electro-acupuncture
      was commenced. A good subjective clinical response was achieved which has been
      maintained by fortnightly treatments. We discuss the prevalence, pathogenesis and
      treatment of painful piezogenic pedal papules. We believe that our patient is the
      first to have 'herniations' at both heel and shin sites and the first to have
      successful sustained pain relief for painful piezogenic pedal papules.

PMID- 9155978
TI  - General practitioner referrals.

PMID- 9155977
TI  - Persistent telangiectatic erythema associated with an automatic implantable
      cardioverter defibrillator.

PMID- 9155980
TI  - Congenital hypertrophy of the lateral nail folds of the hallux in twins.

PMID- 9155979
TI  - Alopecia in liver transplant recipients.

PMID- 9155981
TI  - Pyoderma gangrenosum following treatment with isotretinoin.

PMID- 9155976
TI  - Treatment of angioma serpiginosum using a pulsed tunable dye laser.
AB  - Angioma serpiginosum (AS) is a rare vascular naevoid disorder due to ectatic
      dilation of capillaries in the papillary dermis. The condition is found almost
      exclusively in females who have grouped erythematous punctate lesions usually on
      the lower limbs or buttocks, which may be unsightly. We report five patients with
      AS treated using a Candela SPLT1 pulsed tunable dye laser. All patients had a
      good to excellent response. The lesion resolved in one patient, virtually
      resolved in two and is considerably improved in a further patient in whom
      treatment is continuing. In one patient, the angiomatous lesion improved but the
      patient developed hyperpigmentation at the treatment site and the treatment has
      been temporarily suspended. The results suggest that treatment using the pulsed
      dye laser is very effective for AS and, in most patients, produces an excellent
      cosmetic result.

PMID- 9155982
TI  - Pyoderma gangrenosum in myelodysplasia responding to granulocyte macrophage
      colony stimulating factor (GM-CSF)

PMID- 9155983
TI  - Local intralesional therapy with rhGM-CSF for a large genital ulcer in Behcet's
      disease.

PMID- 9155984
TI  - Merkel cell carcinoma of the skin treated by primary radiotherapy.

PMID- 9155985
TI  - Bullous pemphigoid associated with eosinophilic pustules.

PMID- 9155986
TI  - Proliferation markers Ki67 and PCNA in cutaneous squamous cell carcinomas: lack
      of prognostic value.

PMID- 9155987
TI  - Cytokine dermatosis: reactivation of eczema during interleukin-2 infusion.

PMID- 9155988
TI  - Drug-induced hypersensitivity syndrome and toxic epidermal necrolysis. Treatment
      with N-acetylcysteine.

PMID- 9155989
TI  - Skin lesions as the only manifestation of the hypereosinophilic syndrome.

PMID- 9155990
TI  - Isolated subcutaneous candidal abscess and HIV disease.

PMID- 9155991
TI  - Giant hemifacial angioma and PHACE syndrome.

PMID- 9155992
TI  - Peculiar inflammatory cutaneous metastasis from stomach adenocarcinoma.

PMID- 9155993
TI  - Laboratory abnormalities in granuloma annulare: a case-control study.

PMID- 9155994
TI  - Neuronavigation--the surgeon's sextant.

PMID- 9155995
TI  - Delayed surgery for ruptured intracranial aneurysms: a reappraisal.
AB  - Delayed aneurysm surgery, once standard practice, is now followed by only a
      minority of neurosurgeons. We analysed the outcome of such a policy in 400
      consecutive patients with ruptured aneurysms treated over a 14-year period.
      Despite an 'open door' admissions policy, admitting all patients immediately on
      referral, only 56% arrived within 24 h of the ictus (69% within 72 h). Surgery
      was generally delayed for 8-10 days in patients in Grades 1 and 2; for higher
      grade patients often for longer until their condition was stable. Two-hundred-and
      eighty-seven patients (72%) underwent surgery, 93% on day 8 or later (78% on day
      11 or later). Outcome was assessed at 1 year. For all patients 68% were in
      Glasgow Outcome Scale Grade 1, while 26% had died. Of the operated patients 88%
      were in GOS grade 1, while 5% had died (30-day surgical mortality was 3.5%).
      Fifty-one patients (12.8%) rebled, 30 in the first 10 days. Rebleeding was
      distributed evenly in time over the first 2 weeks. Eighty-four patients
      experienced non-haemorrhagic deterioration (NHD) all but 3 within 10 days. NHD
      peaked at days 4-9. Thirty-three patients died of rebleeding and 16 of NHD, but
      only 12 of the patients who died from rebleeding were fit for operation at
      anytime and might have been considered for early surgery. Two of these patients
      died so soon after admission that surgery could not have been performed leaving
      10 patients who might have been saved by early surgery. We review the theoretical
      advantages of delayed as against early surgery and conclude that it is doubtful
      whether the timing of surgery has any significant effect on management outcome in
      line with the conclusions of the Cooperative Study.

PMID- 9155996
TI  - Stereotactic multiple are radiotherapy. IV--Haemangioblastoma.
AB  - Our initial experience in the treatment of haemangioblastoma using conventional
      external beam radiotherapy and stereotactic radiotherapy (radiosurgery), by the
      linear accelerator method, is reported. Six haemangioblastomas in five patients
      were treated with a mean follow-up of 40 months (range 14-60). Five
      haemangioblastomas in four patients were treated with stereotactic radiotherapy,
      where four showed complete radiological response and the fifth was static.
      Neurological symptoms and signs improved in those patients. The sixth
      haemangioblastoma was situated close to the pituitary and optic chiasm, and was
      treated with conventionally fractionated external beam radiotherapy. The lesion
      showed partial response. No complications were noted in this patient group. This
      series complements and extends the relatively sparse published literature
      demonstrating that radiotherapy is an effective option for treating
      haemangioblastomas. Radiosurgery often lends itself particularly well to these
      discrete lesions allowing highly focused treatment. For patients with multiple
      and metachronous cerebellar haemangioblastomas as part of the von Hipple-Lindau
      syndrome, the data support a policy of conventionally fractionated external beam
      radiotherapy to the whole cerebellum of 50-55 Gy followed, after a period of
      time, by radiosurgery to persisting lesions (patients 3 and 4).

PMID- 9155997
TI  - The role of mebendazole in the surgical treatment of central nervous system
      hydatid disease.
AB  - Although hydatid disease is the most common human disease caused by helminths,
      cerebral and spinal involvement in hydatid disease is rare. Recurrence is common
      when cysts rupture during surgical removal. The authors present the results of
      combined treatment with surgery and mebendazole in four cerebral and five spinal
      cases of hydatid disease. The patients' ages ranged between 4 and 55 years with a
      mean of 26 years. In three of the four cranial patients who received mebendazole
      treatment, the cysts ruptured during surgical removal. Four of the five spinal
      cases had recurrent disease at the time of admission. Mebendazole was started
      immediately after surgery and continued over 12 months. All cases but one are
      stable clinically or radiologically at a mean 27 months follow-up period.

PMID- 9155998
TI  - Recurrent aneurysmal subarachnoid haemorrhage: bleeding pattern and incidence of
      posthaemorrhagic ischaemic infarction.
AB  - This report is based on a consecutive series of 162 patients with aneurysmal
      subarachnoid haemorrhage (SAH), including 22 patients (14%) with recurrent SAH,
      who were treated within 72 h after the most recent bleed. Of the 22 patients with
      recurrent haemorrhage: 68% were in poor clinical condition (Hunt & Hess grade 4
      5); 73% presented with intracerebral haemorrhage (ICH); 41% developed delayed
      ischaemic infarctions from chronic arterial spasm; 14% made a good recovery,
      while 41% died. Of the 140 patients with a single bleed: 34% were in poor
      clinical condition (Hunt & Hess grade 4-5); 33% presented with ICH; 22% developed
      delayed ischaemic infarctions; 53% made a good recovery, while 19% died. Our
      results suggest that a high incidence of intracerebral haemorrhage in conjunction
      with a more severe course of chronic arterial spasm substantially contributes to
      the high morbidity and mortality associated with recurrent SAH. In poor grade
      patients not suitable for acute open surgery, endovascular treatment should
      receive consideration for the prevention of early rebleeding.

PMID- 9155999
TI  - Tuberculomas presenting as isolated intrinsic brain stem masses.
AB  - We document the clinical presentation, management and outcome of histologically
      verified, solitary, intrinsic brain stem tuberculomas in six patients. The
      neurological symptoms and signs in these patients did not distinguish their
      lesions from other intrinsic masses of the brain stem. On contrast-enhanced
      computed tomography (CT), the tuberculomas appeared as ring enhancing lesions in
      three patients and nodular contrast enhancing lesions in the other three.
      Diagnosis was established on the basis of CT-guided stereotactic biopsy in all
      patients. All patients were treated with antituberculous drugs for 18 months.
      Steroid therapy of 2-8 weeks duration was also used in four patients. At a median
      follow-up period of 20 months (range 9-51 months), three patients were
      asymptomatic and the other three were functioning independently with mild
      disability. Although isolated, intrinsic brain stem tuberculoma is an uncommon
      entity, it should be suspected in patients presenting with features of an
      intrinsic brain stem mass and a contrast-enhancing lesion on CT. CT-guided
      stereotactic biopsy usually provides evidence of the inflammatory nature of the
      mass although an aetiological diagnosis is often elusive. Early diagnosis and
      appropriate therapy with antituberculous drugs and steroids usually results in an
      excellent or good outcome in most instances.

PMID- 9156000
TI  - The extradural approach to lesions involving the cavernous sinus.
AB  - We report our experience with five lesions exclusively involving the entire
      cavernous sinus in which an essentially extradural surgical approach was used.
      There were two cases of cavernous haemangioma, two cases of meningioma and one
      case of fungal granuloma. The dural cover of the superior orbital fissure, and
      mandibular and maxillary divisions of the fifth nerve was dissected along with
      the dura of the lateral wall of the cavernous sinus. The presence of a relatively
      large intracavernous bulge due to the tumour assisted in this dissection. The
      contents of the cavernous sinus were exposed from an anterolateral, lateral and
      inferior approach. Through the corridor available between the splayed out cranial
      nerves, a radical resection of the tumour was accomplished in each case. The
      technical advantages of this approach are discussed in light of the anatomy of
      the dural configuration of the lateral wall of the cavernous sinus.

PMID- 9156001
TI  - Pituitary abscess: a series of six cases.
AB  - Pituitary abscess is a rare condition occurring in various age groups. Only about
      a hundred cases have been reported in the literature. We describe six cases that
      constitute 0.6% of all the pituitary lesions operated at this centre in the last
      10 years. All the patients presented with visual symptoms, though systemic
      features of infection were present in only two cases. The abscess was seen in
      association with adenoma in two cases and Rathke's cleft cyst in one. One patient
      developed an abscess following surgery for pituitary adenoma. The offending
      organisms was fungal in two cases, mycobacterium in one, bacterial in one and two
      cultures were sterile. Preoperative diagnosis is difficult and a high degree of
      suspicion in ring enhancing lesions of the sella is required.

PMID- 9156003
TI  - Frontal small craniostomy and irrigation for treatment of chronic subdural
      haematoma.
AB  - A new surgical method for the treatment of chronic subdural haematoma is
      presented. A small craniostomy is made on the superior lateral angle of the
      forehead just beneath the hair line without hair removal using a high-speed
      drill. Through this aperture, evacuation and irrigation of the haematoma can be
      carried out safely. No infections occurred in a series of patients treated in
      this way, and the recurrence rate was 10% (2/20). The surgical wound was
      negligible. Because of its simplicity, and the lack of a need for hair removal,
      the procedure appears to be acceptable as an optional therapeutic modality.

PMID- 9156002
TI  - Aneurysm size: a prognostic factor for rupture.
AB  - For effective management of patients with unruptured intracranial aneurysms,
      prognostic criteria for rupture are needed, of which aneurysm size is a key
      factor. However, the critical size at which an aneurysm becomes hazardous is not
      known. During the last 5 years, 1558 aneurysm patients have been operated on in
      our centre. Of these 1248 presented with a subarachnoid haemorrhage (ruptured
      aneurysms) and 310 without a subarachnoid haemorrhage (unruptured aneurysms). Of
      the ruptured aneurysms 475 (38%) were small in size with a maximum diameter < 6
      mm. Most of these small ruptured aneurysms were located on the anterior
      communicating artery. Of the 310 patients with unruptured aneurysms 253 (81.6%)
      had single aneurysms; 113 (44.7%) of those were small in size. Most of these
      small unruptured aneurysms were located on the middle cerebral artery. The
      remaining 57 patients with unruptured aneurysms harboured multiple aneurysms
      totalling 116 aneurysms; 50% of them were small in size. Our of 160 patients with
      multiple aneurysms presenting with subarachnoid haemorrhage, 34 patients had
      small aneurysm(s) accompanied with medium or large sized aneurysm(s); in nine
      (26.5%) of these 34 patients the small aneurysm was the ruptured one. These data
      suggest that small aneurysms < 6 mm in diameter are not innocuous and hazardous,
      and surgical treatment should be considered for small unruptured aneurysms even
      if they are less than 6 mm in diameter.

PMID- 9156004
TI  - Infarction of a vertebral pedicle causing acute spinal cord compression.
AB  - We present a case of acute spinal cord compression due to haemorrhage following
      recurrent infarction of the right pedicle of the second lumbar vertebra. Such a
      case has not previously been reported and we describe the radiological and
      operative findings. Magnetic resonance imaging was particularly helpful in
      precisely localizing the lesion and planning surgery. The most likely diagnosis
      remained a solitary neoplastic deposit until confirmation of recurrent infarction
      was made on histological examination of the operative specimen. The histological
      findings were also in keeping with the episodic progression of the patients
      symptoms.

PMID- 9156005
TI  - Self-trephination of the skull with an electric power drill.
AB  - There is extensive archaeological evidence of the practice of trephination of the
      skull in many ancient cultures in different parts of the world. We report a case
      of self-trephination of the skull by a patient using an electrical power drill
      subsequently requiring neurosurgical intervention.

PMID- 9156006
TI  - Symptomatic lumbar foraminal epidural varix. Case report and review of the
      literature.
AB  - Symptomatic epidural varix is rarely described in the literature and is difficult
      to diagnose by CT. We present a case of symptomatic foraminal epidural varix
      associated with bilateral spondylolysis simulating an extreme lateral disc
      herniation on CT. The literature is reviewed.

PMID- 9156007
TI  - Cerebellar mutism with subsequent dysarthria in an adult: case report.
AB  - An adult case of mutism and subsequent dysarthria after posterior fossa surgery
      is presented. An EEG performed during the mute phase showed widespread left
      hemisphere abnormality although the CT findings were normal. The possible
      mechanisms underlying this syndrome are discussed.

PMID- 9156008
TI  - The earliest case of extracranial aneurysm of the vertebral artery.
AB  - A lesion is described on the body of C4 from the skeleton of an adult male
      recovered from a 15th century site in Gloucester. The most plausible explanation
      for the lesion is that it represents the negative image of an extracranial
      aneurysm of the vertebral artery and thus is the earliest case described.

PMID- 9156009
TI  - Traumatic haemorrhagic optic neuropathy: case report.
AB  - We report a case of visual loss following haemorrhage into the optic nerve sheath
      following head trauma. The patient showed improvement in visual function
      following decompression of the optic nerve sheath and evacuation of the
      haematoma.

PMID- 9156010
TI  - Osteomyelitis of the skull vault from a human bite.
AB  - We report a case of extensive osteomyelitis of the skull vault from a human bite.
      The presentation and surgical management of this unusual condition is described.
      The microbiological findings are comparable to known patterns of infection after
      human bites. Surgical management and prophylaxis after this injury are discussed.

PMID- 9156011
TI  - Spinal cord stimulation.

PMID- 9156012
TI  - Stereotactic multiple arc radiotherapy. III--Influence of treatment of
      arteriovenous malformations on associated epilepsy.
AB  - Although radiosurgery obliterates the majority of arteriovenous malformations
      (AVMs) and cures patients of further haemorrhage, the perceived beneficial effect
      on the epilepsy associated with it is less certain. Two recent publications
      suggest that radiosurgery benefits the associated epilepsy. In a consecutive
      series of 101 AVM patients presenting for radiosurgery to St Bartholomew's
      Hospital, 24 had a history of fits; 16 were evaluable for analysis of fit
      control. Fifteen of the sixteen patients (94%) had improvement in fit control,
      10/16 (63%) becoming fit free. This improvement appeared to correlate with
      response to treatment on follow-up angiography and in 11/15 patients this
      occurred with no change or a reduction in anticonvulsant in medication. No
      patient suffered a deterioration in the epilepsy. These data are discussed in the
      context of the only two previous reports in the literature and the mechanisms of
      action of treatment.

PMID- 9156013
TI  - Lumbar microdiscectomy in the elderly patient.
AB  - This study retrospectively analysed 60 patients who had undergone microsurgical
      lumbar discectomy at an age of > or = 60 years. The results were compared with
      those obtained in 44 discectomy patients who were operated on during the same
      study period, but not selected for age. Sixty-five operations were performed on
      the elderly group and 49 on the age comparison group. Patients were scored for
      pain relief in a short-term follow-up (2 months) using office visit records. Long
      term follow-ups [mean 6.5 years (elderly) vs 8.8 (comparison) years], obtained by
      a mailed questionnaire, quantified leg and back pain and scored success in return
      to normal activities (RTA) and satisfaction with the results of surgery. In the
      short-term, overall pain relief was highly successful and not significantly
      different in both group [94% (elderly), 98% (comparison)]. Long-term follow-up
      yielded the following successful outcomes (elderly, comparison groups): leg pain
      relief (91%, 86%), back pain relief (76%, 76%), RTA (68%, 87%), and satisfaction
      (81%, 91%). As with other pre- and postoperative parameters, these differences
      were not statistically significant. As the proportion of older individuals
      continues to rise in developed countries, physicians are increasingly faced with
      geriatric patients whose symptoms are caused by herniated lumbar discs. The
      present study indicates that microsurgical discectomy for relief of this
      condition can be performed safely and effectively on these older patients.

PMID- 9156014
TI  - Significance of pupillary reactivity in poor-grade aneurysm patients as a
      prognostic factor and an indication for active treatment.
AB  - Sixty-eight patients with subarachnoid haemorrhage (SAH) who were admitted in a
      comatose state were studied to determine the factors influencing mortality and to
      seek criteria for case management. Overall, the functional recovery (good
      recovery or moderate disability) rate was 33%, with a mortality rate of 50%.
      Bilaterally unreactive pupils on admission was a powerful predictor of death (p <
      0.0001): outcome of these patients was poor regardless of any treatment
      modalities with a mortality rate of 91% (20/22). Initial poor motor response
      (abnormal flexion, extension, or nil) was also significantly related with death
      (p < 0.05). However, motor response was a less powerful predictor than pupillary
      reactivity. Motor response often altered spontaneously during the 12 h after
      admission, whereas pupillary reactivity tended to be stable. Initial reactive
      pupils were shown to be an indicator of spontaneous improvement of motor
      response. These findings indicate that pupillary reactivity may be a reliable
      predictor of outcome in poor-grade SAH patients.

PMID- 9156015
TI  - Neural arch tuberculosis: radiological features and their correlation with
      surgical findings.
AB  - Radiological features of 17 cases of neural arch tuberculosis (NAT), treated
      surgically by the authors, are reviewed and correlated with the operative and
      histopathological findings. The diagnostic accuracy of different imaging
      modalities in the evaluation of this rare, atypical form of spinal tuberculosis
      was found to be very low. Thus, the initial diagnosis was in error in 15 out of
      17 of our cases. Recognition of the radiological diagnostic features of NAT is
      important, not only because they may mimic primary or metastatic spinal
      neoplasms, but also because of the surgical implications. Computed tomography
      (CT) and magnetic resonance imaging (MRI) features correlated most closely with
      the surgical findings, whereas plain spinal radiographs and myelograms were found
      to be non-specific and non-diagnostic.

PMID- 9156016
TI  - Gastroprotection in neurosurgery: the practice in Great Britain.
AB  - The indications for gastroprotection concurrent with corticosteroid use or as
      prophylaxis for stress ulceration in the neurosurgical intensive care unit remain
      unclear. The purpose of this study was to determine to what extent
      gastroprotection is practised in neurosurgical units in the British Isles. Data
      were obtained by questionnaire circulated at the end of 1988 and 1994. Of 92
      surgeons who replied in 1988, 49 routinely used a gastroprotective agent with
      corticosteroids and 47 in patients at risk of stress ulceration. This compares
      with 63 out of 89 surgeons using a gastroprotective agent with steroid
      administration and 60 using prophylaxis for stress ulceration in 1994. The
      gastroprotective agent of choice in 1988 was an H2 antagonist (76) followed by
      antacids (36). In 1994, it was again an H2 antagonist (69), but sucralfate (15)
      was now the second most common agent used. The number of reported peptic ulcer
      complications among those surgeons who did not routinely use gastroprotective
      agents was no higher than those who did. Our findings indicate an increase in the
      administration of gastroprotective agents within neurosurgery. However, the use
      of H2 antagonists in the intensive care unit and the use of gastroprotective
      agents with corticosteroids may not be warranted.

PMID- 9156017
TI  - Comparison between ventriculoatrial and ventriculoperitoneal shunting in the
      adult population.
AB  - A comparison is made between ventriculoperitoneal (VP) and ventriculoatrial (VA)
      shunting in an adult population. Forty-nine patients with VA shunts and 73 with
      VP shunts, as well as six with a combination of the two, in total 128, were
      reviewed. Sixty-eight complications were encountered in 168 operations (40.5%).
      There were two deaths. The infection rate was 2.5%. Distal tube blockage occurred
      after five out of 109 VP shunt operations (79 patients), while four blockages
      occurred in 59 VA shunts (55 patients). In addition, six peritoneal catheters
      escaped from the peritoneal cavity requiring revision. We found the complication
      rate involving the distal end of the shunt to be similar between the two types,
      but favour the ventriculoperitoneal shunting because of the ease of placement and
      the lesser severity of potential complications.

PMID- 9156018
TI  - "Tethered cord syndrome"--recent clinical experience.
AB  - Thirty-three consecutive patients treated surgically for "tethered cord syndrome"
      over a 3-three year period were reviewed. The main presenting complaints were
      back and leg pain, progressive lower limb and spinal deformity, and neurological
      deficits. Untethering of the cord was achieved in 32 patients, in whom the filum
      terminale was divided in 17. There were no serious complications; one patient had
      a CSF leak which required surgical repair. The mean postoperative follow-up was
      15 months and 20 of the patients reported improvement, the rest were unchanged.
      There was no neurological deterioration in any of the patients. Our series
      suggests that cord release in patients with "tethered cord syndrome" improves or
      arrests the progression of neurological deterioration.

PMID- 9156019
TI  - The impact of teleradiology on the inter-hospital transfer of neurosurgical
      patients.
AB  - The aim of this study was to examine the role of teleradiology in the management
      of inter-hospital transfer of neurosurgical patients, especially in terms of
      safety and early therapeutic interventions. Data were collected prospectively,
      comparing events during the inter-hospital transfer of patients from a district
      general hospital to a tertiary neurosurgical centre, before and after
      teleradiology became available. From March to December 1995, 50 referrals made
      without teleradiology were compared with 66 referrals after teleradiology
      installation. Our results showed that for patients referred with teleradiologic
      images, unnecessary transfers were reduced (21%), more therapeutic measures
      before transfer were implemented (27% vs 20%, p = 0.41), adverse events occurring
      during transfer were significantly reduced (8% vs 32%, p = 0.002), and transfer
      time was shortened (72 min vs 80 min, p = 0.38). The potential advantages of this
      system in facilitating safer transfers and faster management of neurosurgical
      emergencies therefore merit further attention.

PMID- 9156020
TI  - Failure of osseous conduction with cervical interbody BOP graft.
AB  - We report three patients treated for cervical radiculopathy by anterior cervical
      discectomy and BOP grafting. Because of recurrent symptoms re-exploration was
      carried out 30 months later in the first case, 10 months in second and 8 months
      in the third case. At reoperation the grafts were disrupted into easily separable
      fibres. Histologically, there were no osteoblast or fibroblast cells or new bone
      formation. We suggest that contrary to the manufacturer's claims, the material
      acts only as a "spacer" and does not conduct bone formation.

PMID- 9156021
TI  - Interactive image-guided surgery of the spine--use of the ISG/Elekta Viewing Wand
      to aid intraoperative localization of a sacral osteoblastoma.
AB  - The intraoperative localization of small osteoid osteomas and osteoblastomas of
      the spine is often difficult. The authors report a patient with a small sacral
      osteoblastoma in whom the experimental use of an Interactive Image-Guidance
      Stereotactic system, to aid localization, is described. The Elekta Viewing Wand
      is a spatial localization device primarily designed for intracranial procedures.
      We evaluated its potential role in the localization and minimally invasive
      excision of a sacral osteoblastoma in this patient. A basic assessment of the
      limitations encountered in extracranial use of this system is presented and
      possible solutions to minimize these problems are discussed.

PMID- 9156022
TI  - Disintegration of cervical intervertebral BOP grafts with neurological sequelae:
      a report of two cases.
AB  - We report the case histories of two patients treated in our unit for cervical
      radiculopathy by anterior cervical discectomy and BOP grafting. Both grafts
      disintegrated within 6 weeks of insertion resulting in increased neurological
      deficit from cervical cord compression. At reoperation fibres from the grafts
      were found to have separated and the larger fragments had extruded into the
      vertebral canal. No evidence of infection was seen, but a foreign body reaction
      was found in one case. Following graft removal the patients improved
      symptomatically although one was left with permanent mild biceps weakness.

PMID- 9156023
TI  - Pharyngo-cutaneous fistula following anterior cervical fusion.
AB  - A 26-year-old man who underwent anterior cervical fusion for a compressed
      fracture of the C5 vertebra developed postoperatively partial extrusion of the
      bone graft, followed by progressive dysphagia and retropharyngeal emphysema.
      Although no definite perforation of the oesophagus or pharynx was detected at
      reoperation, an extensive pharyngocutaneous fistula formed subsequently through
      the operative wound. Open drainage in association with broad spectrum
      antibiotics, continuous nasopharyngeal suctioning, stopping of oral intake and
      gastrostomy feeding resulted in closure of the fistula. However, the fistula
      recurred twice soon after resumption of the oral feeding. The diagnostic
      difficulties in determining when the healing of a pharyngo-cutaneous fistula is
      complete are underlined. In addition, the importance of continued treatment for 4
      6 weeks after first radiological evidence of closure of the fistula is
      emphasized.

PMID- 9156024
TI  - Spontaneous drainage of an infratentorial extradural empyema: case report.
AB  - We describe a 21-year-old male who presented with spontaneous drainage of an
      infratentorial extradural empyema secondary to mastoiditis. Following eradication
      of the primary source, the patient was commenced on high dose intravenous
      antibiotics. Serial computed tomography (CT) revealed complete resolution of the
      pus collection. Antibiotic therapy was successful and no neurosurgical
      intervention was necessary.

PMID- 9156025
TI  - Chronic extradural haematoma with delayed expansion.
AB  - A 35-year-old man became symptomatic 26 months after a head injury. CT showed an
      occipital-suboccipital chronic extradural haematoma (EDH). A surrounding
      membrane, with neovascularisation, was evident, both, on CT and at surgery. This
      unusually long interval between trauma and onset of symptoms suggests that
      delayed expansion of a chronic EDH should be kept in mind if planning
      conservative management. An EDH can be considered 'cured' only after
      disappearance of the membrane and haematoma on CT.

PMID- 9156026
TI  - Primary sellar haemorrhagic melanoma: case report and review of the literature.
AB  - Primary melanoma of the sella turcica is very unusual with only four previous
      cases reported in the medical literature. This report describes a 47-year-old man
      whose headaches, endocrine dysfunction and neuro-imaging suggested a haemorrhagic
      pituitary macroadenoma. The histological examination showed a haemorrhagic
      melanoma. An extensive search for a primary source proved negative. The patient
      underwent three neurosurgical interventions and radiotherapy and died two years
      after presentation. Previous cases of primary melanoma in the pituitary region,
      as well as various hypotheses for this unusual site of origin are reviewed,
      followed by a discussion of the particular characteristics of melanin pigments on
      MRI. This case report illustrates that primary sellar melanoma may present as a
      haemorrhagic adenoma of the pituitary gland and have an unfavourable outcome
      despite repeated neurosurgical interventions and radiation therapy.

PMID- 9156027
TI  - Spinal cord herniation after stabbing injury.
AB  - A 19-year-old man presented with delayed paraplegia on the second day after a
      stab injury of the spine. Magnetic resonance imaging showed herniation of the
      spinal cord through the dural defect. After emergency surgery, his paraplegia
      recovered leaving a Brown-Sequard syndrome immediate after injury. Spinal cord
      herniation should be considered as one of the possible factors in patients
      developing neurological deterioration after a stab injury of the spine. The
      possible pathogenesis of symptomatic non-spontaneous spinal cord herniation is
      discussed.

PMID- 9156028
TI  - Posterior interbody fusion after spinal tumour surgery.

PMID- 9156029
TI  - Unusual multicystic lesions of the brainstem are mesencephalo-thalamic expanding
      lacunae.

PMID- 9156030
TI  - Physiological cell death in endocrine-dependent tissues: an ovarian perspective.

PMID- 9156032
TI  - An assessment of optimal hydrocortisone replacement therapy.
AB  - OBJECTIVE: To assess the management of hydrocortisone replacement therapy in one
      institution, and derive recommendations for optimum starting and maintenance
      replacement therapy with hydrocortisone. DESIGN: Retrospective survey of clinical
      management using a clinical information system and the patient case notes.
      PATIENTS: Using the department's clinical information system, 210 patients were
      identified who had been treated with hydrocortisone. Case notes were reviewed and
      130 patients were identified whose records contained the results of at least one
      valid hydrocortisone day curve. Data on 174 day curves performed on these
      patients (65 on twice daily and 109 on thrice daily hydrocortisone regimes)
      formed the basis of this analysis. METHODS: Hydrocortisone day curves had been
      performed as part of routine clinical management: patients collected a 24 h urine
      for free cortisol on the day prior to the test and took their morning
      hydrocortisone at the normal time, at home, on wakening. During a day-case
      attendance serum cortisol was then measured at 0900 h, 1230 h (prior to any
      lunchtime dose) and 1730 h (prior to the evening dose). 'Optimal replacement' was
      arbitrarily defined as that dose which achieved a UFC and 09:00 h cortisol within
      the reference range for the normal population (to avoid over-replacement)
      combined with 1230 h and 1730 h cortisol above 50 nmol/l, and ideally above 100
      nmol/l (to avoid under-replacement). Raw data from all hydrocortisone day curves
      was analysed in an Excel spreadsheet to determine the effect of different dose
      regimens on the percentage of patients achieving each and all of these 4
      criteria, and on an overall 'quality score' (comprising 1 point for each of the 4
      criteria attained). RESULTS: Patients on twice daily hydrocortisone regimes
      achieved optimal replacement in 15% of cases compared to 60% on thrice daily
      regimes (P < 0.001 by chi 2); mean overall 'quality scores' for these regimens
      were 2.72 and 3.49 respectively (P < 0.001 by t-test). Of individual dose
      regimens with sufficient cases for valid comparison, a dose of 10 mg/5 mg/5 mg
      (rising/lunch/evening) achieved optimal replacement in 66% and mean 'quality
      score' of 3.62 (n = 53), compared to 50% and 3.32 for 10 mg/ 10 mg/5 mg (n = 28)
      and 10% and 2.48 for 20 mg/-/10 mg (n = 29). CONCLUSIONS: The use of arbitrary,
      but logical, criteria to assess the quality of hydrocortisone replacement
      regimens indicates that optimal replacement is achieved with thrice daily
      hydrocortisone regimens, and that the traditional twice daily regime results in a
      0900 h cortisol above normal in one-third, and late afternoon cortisol below 50
      nmol/l in one-half of patients thus treated. An appropriate starting dose of
      hydrocortisone of 10 mg/5 mg/5 mg (rising/lunch/evening) is suggested, with
      subsequent individual adjustment based on simple hydrocortisone day curves.

PMID- 9156031
TI  - Glucocorticoid replacement therapy: are patients over treated and does it matter?
AB  - BACKGROUND AND OBJECTIVES: Adequate assessment of patients on glucocorticoid
      replacement therapy is of great importance to avoid the consequences of under or
      over treatment, but no simple test is available for this. The aims of this study
      were (1) to assess adequacy of glucocorticoid replacement in hypoadrenal
      patients, (2) to correlate serum cortisol levels (cortisol day curve) with 24
      hour urine free cortisol excretion and (3) to assess the impact of glucocorticoid
      dose optimization on markers of bone formation and bone resorption. DESIGN: Cross
      sectional study of current replacement therapy and a prospective study of the
      effect of dose alteration on bone turnover markers. PATIENTS: Thirty-two
      consecutive patients on replacement glucocorticoid therapy (12 Addison's disease,
      20 hypopituitarism) from a University teaching hospital out-patient department.
      MEASUREMENTS: Serum and urinary cortisol, osteocalcin, N-telopeptide of type I
      collagen (NTX) and bone mineral density. RESULTS: 28/32 (88%) patients required a
      change of therapy; 24/32 (75%) a total reduction in dose, 18/32 (56%) a change in
      replacement therapy regimen or drug and 14/32 (44%) both changes. The mean daily
      dose of hydrocortisone was reduced from 29.5 +/- 1.2 to 20.8 +/- 1.0 mg. A
      significant correlation was found between peak cortisol and 24-hour urine free
      cortisol/ creatinine (Spearman correlation r = 0.60, P < 0.0001; n = 51).
      Following hydrocortisone dose reduction, median osteocalcin increased from 16.7
      micrograms/l (range 8.2-65.7) to 19.9 micrograms/l (8.2-56.3); P < 0.01, with no
      change in the NTX/creatinine ratio. CONCLUSIONS: A high proportion of patients on
      conventional corticosteroid replacement therapy are over treated or on
      inappropriate replacement regimens. To reduce the long term risk of osteoporosis,
      corticosteroid replacement therapy should be individually assessed and over
      replacement avoided.

PMID- 9156033
TI  - The assessment of glucocorticoid replacement therapy.

PMID- 9156034
TI  - Elevation of circulating proadrenomedullin-N terminal 20-peptide in
      thyrotoxicosis.
AB  - BACKGROUND AND OBJECTIVE: Adrenomedullin (AM) is a recently discovered peptide
      which has potent vasodilatory activity. We have found that the plasma
      adrenomedullin level is elevated in hyperthyroidism, suggesting a potential role
      of AM in the decrease of vascular resistance in thyrotoxicosis.
      Proadrenomedullin, a precursor of adrenomedullin, yields another peptide termed
      proadrenomedullin-N terminal 20-peptide (PAMP). PAMP also has potent vasodilatory
      activity. Although the regulation of secretion of AM and PAMP is not fully
      understood and the mechanism by which the plasma AM level is elevated in
      hyperthyroidism remains unknown, it is of interest to determine the plasma
      concentration of PAMP in thyrotoxicosis. DESIGN AND PATIENTS: We measured the
      plasma concentration of immunoreactive AM and PAMP in newly recruited untreated
      thyrotoxic Graves' patients using specific antibodies to each peptide. RESULTS:
      Not only AM, but also the plasma concentration of PAMP in thyrotoxic patients was
      significantly (P < 0.01) elevated (4.7 +/- 0.9 pmol/l), compared to that in
      control subjects (2.6 +/- 0.8 pmol/l). The correlation was marginally significant
      between the plasma AM concentration and serum free thyroid hormone levels. The
      plasma PAMP level tended to be more elevated when thyrotoxicosis was severe but
      the correlation was not statistically significant. Correlation was not
      demonstrated between the AM and PAMP levels in thyrotoxic patients. CONCLUSIONS:
      Elevation of the plasma adrenomedullin and proadrenomedullin-N terminal 20
      peptide levels raises the possibility of involvement of these vasodilatory
      peptides in the haemodynamic changes in thyrotoxicosis.

PMID- 9156035
TI  - Acute administration of hexarelin stimulates GH secretion during day and night in
      normal men.
AB  - OBJECTIVE: Hexarelin is a synthetic hexapeptide with potent GH-releasing activity
      in both animals and men. The aim of this study was to investigate the effect of a
      bolus injection of hexarelin given in the morning during wakefulness and during
      nocturnal sleep in a group of normal adult men. DESIGN AND SUBJECTS: Eight normal
      men, aged 21-33 years, of normal height and within 10% of ideal body weight were
      studied. All subjects received in random order saline or hexarelin (2
      micrograms/kg) in the morning between 0800 and 0900 h after they had fasted
      overnight. The same experiments were performed during nocturnal sleep in the same
      subjects. Saline or hexarelin were injected within 30 minutes after the onset of
      sleep between 2300 and 2400 h. Sleep was recorded by visual inspection.
      MEASUREMENTS: In all four test sessions blood samples were taken 30, 15 minutes
      and immediately before the injection of saline or hexarelin and then every 15
      minutes for 2 hours. GH was measured by an immunoradiometric assay. All values
      are expressed as peak GH levels or as area under the curve (AUC) calculated by
      trapezoidal integration. RESULTS: Mean peak GH concentrations after hexarelin
      during the morning (58.2 +/- 4.7 micrograms/l) (GH micrograms/l l x 2 = mU/l)
      were not different from those observed during sleep (61.2 +/- 4.3 micrograms/l).
      The rate of disappearance of GH from plasma was slower during sleep (t1/2 = 64.9
      +/- 14.8 min) than during morning hours (t1/2 = 24.9 +/- 1.4 min, P < 0.01). Mean
      AUC responses to hexarelin during sleep (1466 +/- 145 micrograms.min/l) were
      significantly higher than during morning hours (903 +/- 94 micrograms.min/l, P <
      0.001). CONCLUSIONS: These results show that GH responsiveness to a growth
      hormone releasing peptide is preserved during the night. This could be exploited
      for diagnostic and/or therapeutic purposes.

PMID- 9156036
TI  - Reduced expression and normal nucleotide sequence of androgen receptor gene
      coding and promoter regions in a family with partial androgen insensitivity
      syndrome.
AB  - BACKGROUND AND OBJECTIVES: Androgen insensitivity syndrome (AIS) is an X-linked
      disorder of XY males characterized by varying degrees of impaired
      masculinization. In many AIS cases, mutations have been identified in the coding
      sequence of the human androgen receptor (AR) gene which impair receptor function.
      Cases have also been reported in which reduced AR mRNA expression may contribute
      to AIS in association with AR gene mutations. The purpose of this study was to
      define the molecular basis of AIS in members of a family with clinical and
      laboratory features of partial androgen insensitivity (PAIS). DESIGN: Genital
      skin fibroblast (GSF) cultures were established from foreskin tissue for androgen
      receptor binding analysis. Genomic DNA was obtained from blood leucocytes for AR
      gene nucleotide sequence analysis. AR mRNA levels were determined in total RNA
      extracted from GSF cultures. PATIENTS: Three related subjects with perineo
      scrotal hypospadias, bifid scrotum and microphallus were studied. The family
      pedigree of these subjects suggested an X-linked pattern of inheritance. Hormone
      assay results were consistent with AIS. MEASUREMENTS: AR binding capacity and
      affinity were determined in three subjects and compared with unaffected male
      controls. The coding sequence and 1.4 kb of promoter region of the AR gene were
      amplified in overlapping fragments by polymerase chain reaction from genomic DNA
      and sequenced. GSF AR mRNA was measured by a competitive PCR technique. RESULTS:
      In the PAIS subjects, AR affinity in cultured GSF was normal (Kd = 0.24, 0.30,
      0.48 vs 0.27 +/- 0.07 (SD) nmol/l) but binding capacity was reduced (Bmax = 0.31,
      0.36, 0.27 vs 1.26 +/- 0.37 (SD) fmol/microgram DNA). Sequence analysis of the
      CAG repeat polymorphism within exon 1 of the AR gene showed that both mothers
      were heterozygous at this locus, and that the three subjects had inherited the
      same allele. GSF AR mRNA levels were reduced in all three patients compared with
      controls (0.25, 0.74 and 0.74 vs 3.8 +/- 0.9 (SEM), range 1.8-7.3 amol/microgram
      total RNA). The nucleotide sequences of the entire AR coding region and of a 1.4
      kb segment containing the promoter region were normal. CONCLUSION: Members of
      this family with clinical and biochemical evidence of X-linked partial androgen
      insensitivity syndrome demonstrated normal androgen receptor binding affinity and
      androgen receptor gene nucleotide sequence but reduced androgen receptor binding
      capacity and reduced androgen receptor mRNA. These results suggest that partial
      androgen insensitivity syndrome in this family may be caused by reduced
      expression of a normal androgen receptor gene.

PMID- 9156037
TI  - Serum leptin concentrations in patients with anorexia nervosa, bulimia nervosa
      and non-specific eating disorders correlate with the body mass index but are
      independent of the respective disease.
AB  - OBJECTIVE: Leptin, the product of the ob gene, is a recently discovered hormone
      secreted by adipocytes. Serum leptin concentrations increase in correlation with
      the percentage of body fat, but little else is known about the physiological
      actions of leptin in humans. The aim of this study was to determine the role of
      leptin in severe eating disorders, and whether its levels are correlated with the
      specific disease or exclusively with body weight. TESTS: Serum concentrations of
      human leptin were analysed by specific radioimmunoassay and compared with the
      individual body mass indexes (BMI). The correlations between serum leptin
      concentrations and BMI, age and height were analysed. PATIENTS: A total of 65
      women were studied: 25 patients with anorexia nervosa, 20 women with bulimia
      nervosa, 6 women with a diagnosis of nonspecific eating disorder, and 14 normal
      weight women who acted as controls. At the time of the study, the patients were
      non-cured, under treatment, and at different stages of therapeutic evolution.
      MEASUREMENTS: Plasma leptin levels were measured by specific radioimmunoassay.
      RESULTS: The mean serum leptin in the normal-weight women was 10.5 +/- 1.1
      micrograms/l, compared with 7.6 +/- 1.1 micrograms/l in the anorexia nervosa
      patients (P < 0.05). This reduction in leptin levels was paralleled by the
      differences in BMI (21.4 +/- 0.4 vs 18.8 +/- 0.2) P < 0.05. These differences
      between the controls and anorexia nervosa patients were not observed in patients
      with bulimia nervosa who had a mean serum leptin level of 9.9 +/- 1.4
      micrograms/l and BMI of 21.3 +/- 0.6, neither significantly different from
      controls. On the contrary, patients with non-specific eating disorders showed a
      large reduction in BMI (17.9 +/- 1.2, P < 0.05 vs control), and a parallel
      reduction in serum leptin levels, 4.5 +/- 1.0 (P < 0.05 vs controls). When
      individual values of leptin were plotted against BMI a wide range was observed in
      all groups; in the control subjects from 5.6 to 17.7 micrograms/l, in anorexia
      nervosa patients from 2.1 to 28.1 micrograms/l, in patients with bulimia nervosa
      between 2.6 and 25.9 micrograms/l, and in women with non-specific eating disorder
      from 2.0 to 8.9. No correlation was observed with the specific disease but in
      each group a significant correlation was observed only with BMI. CONCLUSIONS:
      Serum leptin levels in three groups of patients affected by severe eating
      disorders are not related to the specific pathology but are correlated with the
      individual BMI. The analysis of leptin values may be a useful index of assessing
      the adipose tissue stores in the clinical setting, but will be of no help for
      diagnosis nor prognosis of severe eating disorders.

PMID- 9156039
TI  - Longitudinal changes of bone mineral density and bone turnover in postmenopausal
      women on thyroxine.
AB  - OBJECTIVE: The skeletal risks of subclinical hyperthyroidism in postmenopausal
      women on replacement thyroxine remain controversial. The aims of this study were
      to determine (1) the relationship between bone turnover and TSH levels and (2)
      whether reduction of thyroxine (T4) dose in postmenopausal women who have
      suppressed TSH levels is beneficial to bone mineral density (BMD) and bone
      turnover. DESIGN: A prospective study over 2 years of post-menopausal women
      treated with T4 with an age- and sex-matched healthy control group. PATIENTS AND
      MEASUREMENTS: Sixty-four post-menopausal women, ages 47 to 74 (61 +/- 9, mean +/-
      SD), on T4 for between 2 and 14 years. Patients were divided into three groups:
      group 1 (n = 23) with normal serum TSH levels, group 2 (n = 18) with suppressed
      serum TSH levels and group 3 (n = 23) with a history of thyroidectomy and
      suppressed TSH levels (patients with thyroid cancer). Thirty-six age-matched
      healthy postmenopausal women were recruited as a control group. Bone mineral
      density (BMD), measured by dual-energy X-ray absorptiometry and bone turnover,
      were evaluated at baseline and over 2 years in the four groups. Serum TSH levels
      were measured every 6 to 12 months. In group 2, the dose of T4 was reduced after
      the baseline measurement and serum TSH levels were remeasured 1 to 4 months
      later. Serum TSH levels returned to the reference range after the reduction of T4
      dose in group 2. RESULTS: The serum TSH level, after log transformation, was
      negatively correlated with serum levels of osteocalcin (BGP), bone alkaline
      phosphatase (BAP) and urinary cross-linked N-telopeptides pyridinoline of type I
      collagen (NTx) (linear correlation, r = -0.41 P < 0.001, r = -0.29 P = 0.01 and r
      = -0.26 P = 0.033), respectively. There was no significant difference in BMD and
      bone turnover between the four groups at either baseline or follow-up (ANOVA, P >
      0.05). The levels of serum BGP, BAP and urinary NTx decreased whereas lumbar
      spine and femoral neck BMD increased significantly in group 2 over 2 years (one
      sample t-test, P = 0.0021, 0.034, 0.0017, 0.011 and < 0.001, respectively). In
      group 2, the rates of change of lumbar spine and femoral BMD were increased
      significantly and the rates of change of serum BGP and urinary NTx were decreased
      significantly compared with other groups (Scheffe test, P < 0.05). CONCLUSIONS:
      In postmenopausal women on T4, bone turnover is related to the serum TSH level
      and a reduction of T4 dose in those with suppressed serum TSH levels can result
      in a decrease in bone turnover and an increase in bone mineral density.

PMID- 9156038
TI  - Growth hormone responses to GH-releasing peptide (GHRP-6) in hypothyroidism.
AB  - OBJECTIVE: Both spontaneous and stimulated GH secretion are reduced in patients
      with hypothyroidism. The mechanisms involved in these alterations are not yet
      fully understood. GHRP-6 is a synthetic hexapeptide that releases GH both in vivo
      and in vitro. Its mechanism of action is unknown, but there is evidence that this
      peptide acts as a functional somatostatin antagonist at pituitary level. The aim
      of this study was to evaluate the GH response to GHRP-6 in patients with primary
      hypothyroidism and in normal controls. DESIGN: Patients with hypothyroidism and
      normal controls were randomly submitted to 3 tests with GHRH (100 micrograms
      i.v.), GHRP-6 (1 microgram/kg i.v.) and GHRH + GHRP-6, on separate days.
      PATIENTS: Eleven patients with primary hypothyroidism were compared with 10
      control subjects. MEASUREMENTS: GH, TSH and free T4 were measured by
      immunofluorometric assay and IGF-1 by radioimmunoassay. RESULTS: Hypothyroid
      patients had markedly lower peak GH values (mean +/- SE micrograms/l) after GHRH
      administration (4.1 +/- 0.9) compared to control subjects (24.9 +/- 5.1). After
      GHRP-6 injection hypothyroid patients had a significantly higher GH release (12.6
      +/- 1.9) than that obtained with GHRH, while in control subjects GH values were
      similar (22.1 +/- 3.6). No significant differences in peak GH responses were
      observed following the administration of either GHRP-6 alone (controls 22.1 +/-
      3.6; patients 12.6 +/- 1.9) or in combination with GHRH (controls 77.4 +/- 15.0;
      patients 52.8 +/- 10.9), despite the trend to smaller responses in hypothyroid
      patients. CONCLUSION: We have shown that patients with primary hypothyroidism
      have higher GH responses to GHRP-6 than to GHRH, which are markedly blunted. When
      GHRP-6 was associated with GHRH, a significant increase in the GH response was
      observed in these patients, which could suggest a role for somatostatin in this
      process. Our data suggest that thyroid hormones modulate GH release induced by
      GHRH and GHRP-6 through different mechanisms. However, additional studies are
      necessary to further elucidate this hypothesis.

PMID- 9156040
TI  - Effect of mifepristone on folliculogenesis in women treated with recombinant FSH.
AB  - OBJECTIVE: To study the mechanism through which mifepristone interrupts
      folliculogenesis. DESIGN: Normally ovulating women undergoing donor intrauterine
      insemination (IUI) treatment were investigated during two menstrual cycles
      treated with gonadotrophins. In the first cycle (FSH cycle), the women were given
      150 IU recombinant FSH (rFSH) s.c. on days 2, 4, 6, 8 and daily thereafter until
      the administration of hCG. During the second cycle (FSH + mifepristone cycle),
      the women received rFSH as above plus mifepristone tablets at a dose of 50 mg/day
      from cycle day 2 until the hCG injection. IUI was performed only in the FSH
      cycles. PATIENTS: Eleven normally ovulating women were studied. The women were
      used as their own controls during the cycle treated with rFSH only. RESULTS: Two
      women became pregnant during the FSH cycle and, therefore, data for comparison
      between the two cycles were available in nine women. In both cycles, only one
      follicle reached the preovulatory stage. However, during treatment with FSH +
      mifepristone the growth of the dominant follicle was temporarily arrested after
      day 8 of the cycle and ovulation was postponed by 2 days on average. Serum FSH
      values increased significantly in both cycles only during the daily
      administration of rFSH, i.e. towards the end of the experimental period when a
      normal growth of the follicle was re-established. On the day of hCG injection, an
      endogenous LH surge had already started in six of the nine cycles treated with
      FSH (67%) but in none of the FSH + mifepristone cycles despite the preovulatory
      oestradiol (E2) levels. Endometrial thickness during the follicular phase and
      serum E2 and progesterone concentrations during the luteal phase, although in the
      normal limits, were significantly lower in the FSH + mifepristone than in the FSH
      cycles. CONCLUSIONS: These results suggest that mifepristone arrests follicular
      development at a stage beyond the recruitment-selection point by delaying the
      growth of the dominant follicle. This is probably achieved through an effect of
      mifepristone on the ovary where it reduces the sensitivity of the selected
      follicle to FSH. Mifepristone may have a potential application for the inhibition
      of the LH surge in superovulation induction programmes.

PMID- 9156041
TI  - Iodine insufficiency and neonatal hyperthyrotropinaemia in Hong Kong.
AB  - OBJECTIVES: 23% of the neonatal hypothyroidism in Hong Kong is transient. The
      present study aims to evaluate iodine excretion in healthy pregnant women in Hong
      Kong and to determine whether iodine insufficiency may occur in the local
      population to account for the type of neonatal thyroid dysfunction seen in our
      screening programme. SUBJECTS: Pilot screening of urinary iodine excretion was
      determined in 253 healthy pregnant women between 32 and 36 weeks gestation. Fetal
      and maternal thyroid function in relation to urinary iodine excretion was
      evaluated in another 55 pregnant women who had given birth to infants with cord
      blood TSH > or = 16 mIU/I (95th percentile of the cord blood TSH screening
      programme) and the results were compared to a control group of 160 healthy women
      whose infants had cord blood TSH < 16 mIU/I. RESULTS: Using a cut-off value of
      0.79 mumol/l, a level as defined by WHO as iodine deficiency, we found that 35.8%
      of the pregnant women had urinary iodine concentrations below this cut off value.
      We demonstrated that the existence of borderline iodine supply affected the
      maternal and fetal thyroid function as evidenced by (i) a negative correlation
      between maternal TSH and urinary iodine concentration, (ii) higher cord blood TSH
      in those infants whose mothers had a low urinary iodine concentration as compared
      to those in whose mothers it was normal, (iii) women who had given birth to
      infants with cord blood TSH > or = 16 mIU/I had lower urinary iodine
      concentrations and serum fT4 levels as compared to mothers who had given birth to
      infants with normal cord TSH levels, and their offspring also had higher cord
      blood thyroglobulin levels. CONCLUSION: Although Hong Kong is not a goitrous
      area, borderline iodine deficiency exists. Iodization of salt in our community
      could obviate the necessity for iodine supplements in pregnant women and other at
      risk groups.

PMID- 9156042
TI  - An audit of the diagnostic usefulness of PRL and TSH responses to domperidone and
      high resolution magnetic resonance imaging of the pituitary in the evaluation of
      hyperprolactinaemia.
AB  - BACKGROUND AND OBJECTIVE: The usefulness of dynamic tests of PRL release in
      determining underlying pathology in hyperprolactinaemic patients is not well
      recognized by endocrinologists, only 15% of whom routinely perform such tests.
      High resolution pituitary magnetic resonance imaging (MRI) has become more widely
      available during the past 5 years and is now generally regarded as the pituitary
      imaging method of choice. Since few prolactinoma patients are now submitted to
      surgery, it is important to ascertain the usefulness of these techniques in
      suggesting a pathological diagnosis. DESIGN: A 3 year retrospective audit of the
      information derived from measurement of PRL and TSH responses to the dopamine
      antagonist domperidone and from high resolution pituitary MRI in patients being
      investigated for hyperprolactinemia in regional endocrine unit. PATIENTS: Eighty
      four patients (10 male, 74 female) whose investigation of hyperprolactinaemia
      included a domperidone test and high resolution pituitary MRI. Patients who had
      domperidone tests performed after pituitary surgery or who did not have pituitary
      MRI were excluded from the analysis. MEASUREMENTS: PRL and TSH were measured
      basally and at 30 and 60 minutes following domperidone (10 mg i.v.) and
      gadolinium-enhanced pituitary MRI was performed in all patients. RESULTS: 20
      patients had a normal PRL response to domperidone (defined as PRL30/PRL0 > 3) and
      this group included five patients in whom hyperprolactinaemia was not sustained.
      Pituitary MRI showed evidence of a microadenoma in only two patients, imaging
      being unequivocally normal in the majority. Sixty-four patients had an abnormal
      PRL response to domperidone and 18 of these had a macrolesion (nine
      prolactinomas, nine other tumours). Pituitary MRI was performed in the remaining
      46 patients with abnormal PRL response to domperidone and suggested microadenoma
      in 29 (63%), identified other structural abnormalities in six cases but was
      entirely normal in 11 cases. Neither the basal PRL level nor the TSH response
      could refine the diagnosis further because of overlap between the various
      subgroups. CONCLUSIONS: The majority of patients with a normal dynamic response
      of PRL to domperidone had a normal or near normal pituitary MRI scan. In the two
      cases where an abnormality was detected it could have been an incidental
      microadenoma or cyst, thus suggesting that pituitary scanning could normally be
      omitted in patients whose PRL response to domperidone is normal (24% of our
      total). The group of patients with an abnormal dynamic response of PRL to
      domperidone was not generally amenable to further diagnostic refinement by
      considering the degree of hyperprolactinaemia or the TSH response to domperidone
      because of overlap of these parameters between the diagnostic subgroups.
      Therefore any degree of hyperprolactinaemia associated with a blunted PRL
      response to domperidone warrants pituitary imaging.

PMID- 9156043
TI  - Longer term outcome in females with congenital adrenal hyperplasia (CAH): the
      Cardiff experience.
AB  - OBJECTIVE: The outlook for fertility and attaining full adult height is poor in
      women with congenital adrenal hyperplasia. Such outcomes have followed treatment
      regimes with variable ages at onset, compliance rates and monitoring. We review
      final height, vaginal anatomy, ovulation rates and fertility in a group of adult
      females with the disease. DESIGN AND PATIENTS: Sixteen adult females first
      diagnosed in infancy or early childhood were reviewed (age range 17-33 years; 11
      with salt-wasting disease; five with simple virilizing disease). Case note and
      clinical review were combined with daily saliva progesterone and weekend 17
      hydroxyprogesterone estimation in three consecutive menstrual cycles in a
      subgroup of eight patients in the ovulation study. MEASUREMENTS AND ANALYSIS:
      Daily saliva progesterone concentrations were transformed into a cumulative sum
      curve using a computer program. T95 (defined as the number of days from the start
      of the luteal phase saliva progesterone rise, in which 95% of total saliva
      progesterone for the menstrual cycle was obtained) and log C95 (where C95 was
      defined as 95% of total saliva progesterone for the same cycle) were plotted for
      each cycle on a boundary diagram obtained from a normal reference population.
      Weekend saliva 17-hydroxyprogesterone concentrations were compared with published
      nomograms. RESULTS: The majority of patients attained a final height below the
      parental target. Mean standard deviation scores (+/-SEM) and ranges were -1.49
      (+/-0.34) and -4.2 to 0.8 for the patients and -0.38 (+/-0.24) and -1.89 to 0.97
      for their parents. Of the combined group two-thirds had regular menses and one
      third hirsutism; 94% had reconstructive genital surgery with 50% requiring second
      procedures; 77% had an adequate vaginal introitus (of them 84% in the salt
      wasting group and 75% in the simple virilizing group were sexually active). Three
      of five patients with salt-wasting disease and 2/3 with simple virilizing disease
      who had both an adequate introitus and were sexually active conceived, resulting
      in eight pregnancies. In the ovulation study, a 40% ovulation rate was observed
      with good correlation between plasma testosterone concentrations and degree of
      control as assessed by weekend 17-hydroxyprogesterone concentrations.
      CONCLUSIONS: Our study highlights the potential for improved fertility in female
      patients with congenital adrenal hyperplasia, who are treated early, comply with
      long-term treatment and have adequately reconstructed external genitalia.
      Attaining full adult height potential remains a problem.

PMID- 9156044
TI  - Insulin-like growth factor-binding protein-2 in patients with prostate carcinoma
      and benign prostatic hyperplasia.
AB  - OBJECTIVE: Insulin-like growth factor-binding protein (IGFBP)-2 is a major
      prostatic IGFBP and may be involved in regulating prostate growth. Patients with
      prostate carcinoma (PC) have elevated serum IGFBP-2 levels which correlate with
      the specific PC marker, prostate-specific antigen (PSA). The aims of this study
      were (i) to investigate whether elevated serum IGFBP-2 is unique to PC or also
      occurs in benign prostatic hyperplasia (BPH), (ii) to examine the relationships
      among age, PSA and IGFBP-2 levels, and (iii) to examine longitudinal changes in
      serum IGFBP-2 with PSA in PC. DESIGN AND PATIENTS: Sixteen patients (61-83 years)
      with inoperable PC attending the Oncology Unit at a tertiary referral hospital
      were studied. Some serum samples were obtained retrospectively while the majority
      were collected prospectively over 13 months of treatment. The patients with PC
      were compared to eight patients (66-73 years) with histologically-proven BPH and
      seven male control subjects (61-82 years) with no known prostate abnormality.
      MEASUREMENTS: A new IGFBP-2 RIA was developed. Serum PSA (by EIA), and IGFBP-2,
      IGFBP-3, IGF-I and IGF-II (by RIA) were measured in all subjects, and serially in
      patients with PC. RESULTS: Serum IGFBP-2 was significantly higher in PC with high
      PSA (560 +/- 66 micrograms/l, n = 12) than PC with normal PSA (292 +/- 65
      micrograms/l, n = 4, P = 0.02), BPH (364 +/- 61 micrograms/l, P = 0.03) and
      controls (367 +/- 44 micrograms/l, P = 0.04). Mean IGFBP-2 in BPH was not
      different from controls. IGFBP-2 and PSA were significantly correlated with age
      (r = 0.543 and r = 0.433 respectively) and with each other even when the age
      effect was removed. Serum IGFBP-2 and PSA levels changed concordantly in all
      seven PC patients who had serial sampling. Serum IGF-II but not IGF-I or IGFB-3
      was higher in PC and BPH than controls (PC 332 +/- 23 micrograms/l, BPH 359 +/-
      26 micrograms/l vs. controls 241 +/- 37 micrograms/l; P = 0.03 and 0.02
      respectively). CONCLUSIONS: Serum IGFBP-2 levels are uniquely elevated in active
      prostate carcinoma but not. In benign prostatic hyperplasia. In prostate
      carcinoma, serum IGFBP-2 levels closely parallel those of prostate-specific
      antigen and probably reflect tumour burden. The relationship between prostatic
      specific antigen and IGFBP-2 is partially independent of their individual
      relationships with age. Although serum IGFBP-2 is less sensitive than prostate
      specific antigen in prostate carcinoma it may have adjunctive value in its
      management.

PMID- 9156045
TI  - The basal rate of cell proliferation in normal human parathyroid tissue:
      implications for the pathogenesis of hyperparathyroidism.
AB  - BACKGROUND: The basal rate of cell proliferation in the human parathyroid gland
      is generally believed to be low, but has never previously been measured directly,
      although, as in other tissues, it is relevant to the pathogenesis of neoplasia.
      METHODS: We retrieved embedded tissue blocks of parathyroids removed at autopsy
      from 39 patients without hypercalcaemia or abnormal renal function, aged 18 to 76
      years (mean 47.6). New sections were cut and examined for expression of Ki-67, a
      cell-cycle marker, using the MIB-1 antibody with microwave antigen retrieval, and
      tonsil as positive control. Using an eyepiece graticule with unbiased square
      counting frame, positively labelled chief cells were counted in large squares and
      total chief cells in small squares in fields selected by systematic random
      sampling from multiple regions. A minimum of 15 x 10(3) chief cells were
      accumulated in each case. The prevalence of Ki-67 positive cells per 10(4) cells
      (label index or LI) was converted to cell birth rate assuming that the duration
      of Ki-67 expression was 24 hours. In ten cases, the entire section was examined;
      a map of the distribution of the positive cells was reconstructed, and divided
      into outer and inner regions. RESULTS: The geometric mean value for LI was 1.44/
      10(4), and multiplicative SD 2.54. The corresponding geometric mean cell-birth
      rate was 5.24%/year and 95% confidence interval 0.81-33.8%/year. We found no
      significant effect of age, sex, race, or duration of tissue storage. The
      distribution of cells conformed to a Poisson distribution, and there was no
      difference between central and peripheral regions. CONCLUSIONS: (1) Our results
      establish the human parathyroid gland as a conditionally renewing tissue with
      very low basal cell-birth rate; other reports of much higher LI values are
      probably due to selective and consequently biased sampling. (2) Since the total
      number of cell divisions is a major determinant of the total number of mutations,
      our results place some constraints of possible mechanisms for parathyroid
      neoplasia.

PMID- 9156046
TI  - Abnormal effect of cigarette smoking on pituitary hormone secretions in insulin
      dependent diabetes mellitus.
AB  - OBJECTIVE: We observed the effect of smoking two cigarettes on GH, AVP and
      cortisol secretion in patients with diabetes and normal subjects. DESIGN AND
      PATIENTS: We tested 10 male smokers with insulin-dependent diabetes mellitus
      (IDDM) and 10 normal smokers. On a different occasion, normal and diabetic
      smokers were tested with an insulin (0.15 U/kg body weight) tolerance test (ITT).
      MEASUREMENTS: Hypoglycaemia-induced hormonal responses in smokers were compared
      with those observed in 10 diabetic and 10 normal non smokers. RESULTS: All
      subjects showed similar basal GH, cortisol and AVP levels. In the normal
      subjects, cigarette smoking induced a significant increase in circulating GH, AVP
      and cortisol levels, with mean peaks 3.3, 3 and 1.58 times higher than baseline,
      respectively. Smoking-induced hormonal responses were significantly higher in
      diabetics (mean peak was 5.2 times higher than baseline for GH, 4.0 for AVP and
      1.83 for cortisol). Insulin induced a similar hypoglycaemic nadir in all subjects
      at 30 minutes, even though the diabetic subjects had a delayed recovery in blood
      glucose levels. GH and AVP responses to hypoglycaemia were significantly higher
      in diabetic (mean peaks 11.5 and 3.2 times higher than baseline, respectively)
      than in normal (mean peaks 7.3 and 1.9) non-smokers, whereas these groups showed
      similar cortisol responses (mean peak 2.3 times higher than baseline). Smoking
      did not change any hypoglycaemia-induced hormonal rise in the normal controls,
      whereas it significantly enhanced GH, AVP and cortisol levels (mean peaks 14.5, 4
      and 3.8 times higher than baseline, respectively) in diabetics. CONCLUSIONS: In
      patients with IDDM, cigarette smoking not only elicits higher GH, AVP and
      cortisol responses than in normal subjects, but also enhances the counter
      regulatory hormone responses to insulin-induced hypoglycaemia. These findings
      suggest interactions between nicotine inhaled with cigarette smoking and diabetes
      induced neuroendocrine alterations.

PMID- 9156047
TI  - Molecular diagnosis of von Hippel-Lindau disease in a kindred with a predominance
      of familial phaeochromocytoma.
AB  - OBJECTIVE: To study the presence of germline mutations in the von Hippel-Lindau
      gene (vhl) in a kindred with a predominance of familial phaeochromocytoma in
      order to confirm the diagnosis of von Hippel-Lindau disease (VHLD) as well as to
      identify asymptomatic members. DESIGN: DNA extracted from peripheral blood was
      amplified by the polymerase chain reaction using oligonucleotide primers
      corresponding to exon 3 of the vhl gene. Specific mutations in codon 238 were
      screened by restriction endonuclease digestion of PCR products with Msp I. The
      results were confirmed by DNA sequence analysis. PATIENTS: Two generations of a
      family consisting of 15 individuals were studied. RESULTS: A germline missense
      point mutation at codon 238 of the vhl gene (CGG-->TGG; Arg-->Trp) was detected
      in all patients with phaeochromocytoma and in only one of the asymptomatic family
      members. CONCLUSION: Mutational analysis of the vhl gene in patients with
      familial phaeochromocytoma may permit specific diagnosis of von Hippel-Lindau
      disease, and is a good method for the identification of asymptomatic individuals
      at risk of von Hippel-Lindau disease.

PMID- 9156048
TI  - Improved glucose tolerance after effective lipid-lowering therapy with
      bezafibrate in a patient with lipoatrophic diabetes mellitus: a putative role for
      Randle's cycle in its pathogenesis?
AB  - This report describes a patient with lipoatrophic diabetes mellitus (LDM), which
      is a rare clinical syndrome characterized by lipoatrophy and severe insulin
      resistance. Although a genetic abnormality is suspected in the development of
      LDM, no functional mutations in key domains of the insulin receptor gene were
      detected. Therapy was directed primarily at decreasing the availability of non
      esterified fatty acids (NEFA), and thereby improving glucose tolerance (Randle's
      cycle), by the administration of a lipid-lowering drug, bezafibrate. Serial
      changes in fasting levels of the hormones of glucose homeostasis and lipids were
      measured, as well as glucose and insulin responses to a 75-g oral glucose
      challenge at onset and following 3 and 6 months of fibrate therapy. Progressive
      reductions in the patient's levels of triglycerides and NEFA were paralleled by
      an improvement in beta-cell function, a decrease in insulin resistance, and the
      attainment of normal glucose homeostasis. We conclude that the pathogenesis of
      LDM may be related primarily to abnormal regulation of lipid, rather than
      glucose, metabolism.

PMID- 9156049
TI  - 17 beta-hydroxysteroid dehydrogenase deficiency with minimal virilization and
      spontaneous reduction of serum androgens to normal female levels.
AB  - The testosterone biosynthesis defect, 17 beta-hydroxysteroid dehydrogenase
      deficiency, is generally characterized by marked virilization at puberty of
      children raised as females. We describe an unusual case with a persistent female
      body habitus presenting with primary amenorrhoea and mild facial hirsutism.
      Whilst awaiting gonadectomy, serum androgen concentrations were observed to fall
      spontaneously to within the adult female reference ranges. Location of the gonads
      was a problem and was finally achieved by magnetic resonance imaging.

PMID- 9156050
TI  - Intractable hypercalcaemia due to parathyroid hormone-related peptide secretion
      by a carcinoid tumour.
AB  - Hypercalcaemia, a common complication of malignancy, may result from either the
      lytic effect of multiple osseous metastases or the effect of tumour-derived
      humoral factors. Excessive secretion of parathyroid hormone-related peptide
      (PTHrP), a major cause of humoral hypercalcaemia of malignancy, has been
      incriminated as the cause of hypercalcaemia in patients with lung, breast, renal,
      head and neck and, occasionally, haematological malignancies. Carcinoid tumours,
      while frequently the source of ectopic hormone secretion, are infrequently
      associated with hypercalcaemia. We report the case of a 59-year-old woman with
      fulminant hypercalcaemia due to excessive PTHrP secretion from a hepatic
      carcinoid and we present the change in her serum PTHrP concentrations during
      infusion of a somatostatin analogue.

PMID- 9156051
TI  - The effects of smoking on remission and relapse of Graves' disease.

PMID- 9156052
TI  - Pituitary apoplexy after leuprolide administration for carcinoma of the prostate:
      what's new?

PMID- 9156053
TI  - Human immunodeficiency virus in otolaryngology.

PMID- 9156054
TI  - The management of aural polyps.

PMID- 9156055
TI  - The incidence and detection of HPV in the upper aerodigestive tract using brush
      and biopsy techniques.
AB  - The association between human papillomavirus (HPV) and squamous carcinoma is well
      established. In the polymerase chain reaction (PCR) we have an effective
      technique for detecting small quantities of viral DNA, but the assay requires
      tissue taken at endoscopy to reveal the presence or absence of HPV. Brushings
      have been used effectively elsewhere in the body to obtain cytological material.
      This study set out to ascertain if sufficient viral DNA could be obtained, using
      a laryngeal brushing and the PCR, to detect the presence or absence of HPV. Six
      patients with squamous carcinoma of the larynx and seven controls who were having
      laryngoscopy for other reasons underwent laryngeal biopsy. In addition, in the
      patients with carcinoma, biopsies were taken at the tumour margins and brushings
      from both sites. The samples were tested for the presence of HPV types 6, 11, 16,
      18 and 31 by means of the PCR. The distribution of HPV types was as expected in
      the biopsy specimens, but only one brushing detected any HPV type at all. We
      conclude that laryngeal brushing is an inadequate technique for assessing the
      presence of HPV in the larynx.

PMID- 9156056
TI  - Audiological findings in glomus tumours.
AB  - Glomus tumours involving the middle ear and the cerebellopontine angle are
      reported with emphasis on audiological findings. Magnetic resonance imaging
      (MRI), angiographic and pathological results are presented. Audiological tests,
      including impedance audiometry, evoked otoacoustic emissions and auditory
      brainstem responses, are valuable in evaluation of the effect of glomus tumours
      on the auditory system as well as their pathological extent.

PMID- 9156058
TI  - Cochlear implantation in the presence of chronic suppurative otitis media.
AB  - Nine patients are presented who underwent cochlear implantation in the presence
      of chronic suppurative otitis media. Four had a simple tympanic membrane
      perforation, four had a pre-existing mastoid cavity and one had cholesteatoma in
      the ear chosen for implantation. Patients with a simple perforation had a staged
      procedure with myringoplasty followed by cochlear implantation after an interval
      of three months. Patients with cholesteatoma or with an unstable mastoid cavity
      were also staged. A mastoidectomy or revision mastoidectomy was performed with
      obliteration of the middle ear and mastoid using a superiorly pedicled temporalis
      muscle flap and blind sac closure of the external meatal skin. After a further
      six months a second stage procedure was performed to confirm that the middle-ear
      cleft was healthy and to insert the implant. Patients presenting with a stable
      mastoid cavity underwent obliteration of the cavity and implantation of the
      electrode as a one-staged procedure. To date there have been no serious problems
      such as graft breakdown, recurrence of disease or implant extrusion, and all
      patients are performing well.

PMID- 9156057
TI  - Evaluation of hearing loss with auditory brainstem responses in the early and
      late period of bacterial meningitis in children.
AB  - The hearing function of 50 children with bacterial meningitis was evaluated at
      the second and 10th days, and eight weeks after admission with auditory brain
      system responses (ABR) to investigate whether meningitis causes hearing loss.
      Normal values were obtained in all tests from both ears of 24 patients (48 per
      cent). Twelve patients (24 per cent) had temporary, and seven (14 per cent)
      patients had persistent mild degree hearing loss. Severe hearing loss was
      detected bilaterally in five (10 per cent) patients and unilaterally in two (four
      per cent) patients. Patients, with other complications such as subdural effusion,
      convulsion, brain oedema and paralysis were found to have a higher incidence of
      hearing loss. We observed that patients treated with dexamethasone had 7.7 per
      cent persistent hearing loss, 11.6 per cent mild hearing loss, 34.6 per cent
      transient hearing loss, but in the group who did not receive dexamethasone there
      was 19.2 per cent persistent hearing loss, 15.3 per cent mild hearing loss and
      11.6 per cent transient hearing loss. There were other significant differences
      between the two groups in restoration of normal body temperature, the CSF/plasma
      glucose concentration ratio was elevated, CSF (cerebro-spinal fluid) protein
      concentration was decreased and the cell count in the CSF was decreased in the
      dexamethasone group, significantly more than the group who were not receiving
      dexamethasone. The hearing loss tended to be more frequent among younger
      children.

PMID- 9156059
TI  - Revision stapes surgery.
AB  - This paper reports on the analysis of 332 otosclerosis revision operations. The
      results have been evaluated with reference to the type of the procedure at
      primary surgery, the alleged cause of failure and the applied technical solution.
      The need for revision surgery was found higher after primary total stapedectomy
      (3.4 per cent) than after partial stapedectomy (2.2 per cent) or stapedectomy
      (two per cent). The reason for revision varied according to the originally
      applied technique eg a migrated piston, a too short piston and a lateralized
      graft are almost exclusively found after total stapedectomies. The median hearing
      gain after revision of stapedectomy and partial stapedectomy was higher (20 dB
      and 18 dB respectively) than that after revision surgery for total stapedectomy
      (12 dB), but significantly lower than hearing gain after primary surgery (32 dB).
      Revisions yielded better results in the case of primary interventions with the
      use of a piston or pistonwire than in the case of primary interventions with a
      wire-type prosthesis. The risk for sensorineural loss (one per cent) was not
      higher than in primary surgery.

PMID- 9156060
TI  - Surgical aspects of paediatric cochlear implantation.
AB  - Cochlear implantation in the paediatric population is now an accepted method of
      rehabilitating profoundly or totally deaf children. The problems of cochlear
      implantation in children with other significant medical problems are examined. A
      retrospective review of the records of the first 45 children implanted at our
      centre was carried out. The review focused on surgical factors and outcome in
      addition to variations in technique which have occurred since the programme
      began. Congenital hearing loss was the most common indication for implantation.
      Fifteen children (33 per cent) had other medical problems. Three cases of flap
      breakdown (two occurring after direct trauma to the package bed) and one case of
      a misplaced electrode requiring re-implantation accounted for the only major
      complications to date. Minor complications included hypertrophic scar formation
      and post-operative wound infection. All children were using their implants at the
      time of this review, but two have subsequently been explanted. Cochlear
      implantation of children with multiple medical problems requires acceptance of a
      slightly higher risk of complications.

PMID- 9156061
TI  - A practical approach to ultrasound of cervical lymph nodes.
AB  - Although the role of high resolution ultrasound (US) in evaluating cervical nodes
      is well established, it is often combined with fine needle aspiration cytology
      (FNAC). As a result, US appearances that help in distinguishing the various
      causes of cervical adenopathy are often overlooked and not emphasized. The aim of
      this study is to re-emphasize to the sonologist the US clues that may help in
      differentiating the aetiology of abnormal cervical nodes. We, therefore, present
      the spectrum of US appearances of lymph nodes. One hundred and forty patients
      (702 abnormal nodes) with known pathology were compared with 100 normal subjects
      (1211 nodes). After identifying an abnormal nodes, US features that further help
      in distinguishing between the various pathologies are the distribution of
      lymphadenopathy, echogenicity, calcification, distal enhancement, intranodal
      cystic necrosis, matting and soft tissue oedema.

PMID- 9156062
TI  - Myringotomy and ventilation tube insertion: a ten-year follow-up.
AB  - Eighty children who had myringotomy performed for otitis media with effusion in
      1984 were reviewed in 1994. This had involved surgery on 158 ears. Three aspects
      of ear condition were studied: hearing loss, tympanic membrane perforation, and
      tympanosclerosis. Hearing losses were present in 13 ears (8.2 per cent),
      involving 10 children (12.5 per cent), although losses were under 20 dB in seven
      of these ears (five patients). Of the six ears with losses more than 20 dB (3.8
      per cent), in five patients bilateral losses of 30 dB were due to a recurrence of
      effusions, a large dry posterior perforation was the cause of a 30 dB loss, an
      infected anterior perforation had caused a 30 dB loss, an ear which had a
      cholesteatoma, and had a mastoidectomy and ossiculoplasty in 1987, had a 30-40 dB
      loss, and one ear which had a Type 1 tympanoplasty in 1994 had a 50 dB loss.
      Therefore in only three ears (1.9 per cent) could hearing loss be associated
      directly with myringotomy and ventilation tube insertion. Perforations had
      persisted unilaterally in seven patients, three having had tympanoplasties. Of
      the remaining perforated tympanic membranes, two were free of symptoms, one had
      only a slight hearing loss, and one had a more significant loss with recurrent
      infection. Tympanosclerosis was only found in those ears which had ventilation
      tubes inserted (and not those which had myringotomy only), occurring in 48 ears
      (31 per cent, of 39 per cent of those which had a ventilation tube inserted).
      There was no link between tympanosclerosis and hearing loss. The site of
      tympanosclerosis was not restricted to the site of myringotomy, and in many cases
      was present only in other areas of the tympanic membrane. There was a tendency
      for more extensive tympanosclerosis to occur in those ears which had more
      ventilation tube insertions. The risk of perforation in particular lends support
      to a policy of 'watchful waiting'.

PMID- 9156063
TI  - Cochlear implantation in otosclerosis: a unique positioning and programming
      problem.
AB  - A case is reported in which a Nucleus 22 channel cochlear implant was inserted
      into the basal turn of the cochlea of a patient with advanced otosclerosis. It
      then passed out of the anterior end of the basal turn into an otospongiotic
      cavity related to the cochlea. Seven electrodes were located in the basal turn
      and it was possible to map them sufficiently well for the patient to derive
      considerable benefit from the implant. The problem of implant induced facial
      nerve stimulation in otospongiosis is also discussed.

PMID- 9156064
TI  - Peritonsillar haematoma.
AB  - We present one patient who was admitted with a peritonsillar haematoma as a
      complication of acute tonsillitis and concomitant warfarin therapy for prosthetic
      aortic valves. While tonsillar haemorrhage as a result of acute tonsillitis has
      been well described, no cases of isolated haematoma formation have been
      documented, nor has it been recognized previously as a complication of long-term
      anticoagulant therapy. We discuss establishing the diagnosis, the likely
      aetiology and implications of this complication.

PMID- 9156065
TI  - Benign necrotizing osteitis of the external auditory meatus.
AB  - Benign necrotizing osteitis of the external auditory meatus is a rare condition
      which occurs in non-diabetic healthy people. The aetiology of the necrotic
      process with the formation of sequestrum in the bony external meatus is unknown.
      It is important to differentiate this benign process from malignant otitis
      externa and radionecrosis of the temporal bone as the management of these
      conditions differs. We present two cases, one managed surgically and the other
      medically, and review the literature. Immediate surgical excision of the
      sequestrum is advocated instead of long-term medical therapy and waiting for it
      to separate spontaneously.

PMID- 9156066
TI  - A rare case of laryngeal myxoma.
AB  - We report a rare case of laryngeal myxoma in a 57-year-old Japanese man. Except
      for a five-year history of gradually progressive hoarseness, he had been in good
      health. Video-stroboscopic examination revealed a solid mass in the anterior
      third of the right vocal fold. Phonosurgery performed with a microscope showed
      that the mass was encapsulated and located between the epithelium and vocal fold
      ligaments of the right vocal fold. This hard, elastic mass which measured 7 mm in
      diameter, was diagnosed as a myxoma. Only three cases of myxoma of the larynx
      have been reported in the English literature, with only one other case involving
      the vocal fold.

PMID- 9156067
TI  - Central nervous system complications of acute tonsillitis.
AB  - Acute tonsillitis is a common infection of early childhood which may even run a
      self-limiting course without antibiotic therapy in some cases. Complications are
      encountered infrequently and rarely assume a life-threatening propensity. Central
      nervous system involvement has not to our knowledge been described in association
      with tonsillitis without local abscess formation. We describe three cases in
      which acute tonsillitis/peritonsillitis was complicated by major central
      neurological sequelae. The neurological complications encountered in young
      previously healthy adults were: facial palsy and hemiplegia; superior sagittal
      sinus thrombosis with communicating hydrocephalus and papilloedema; Guillain
      Barre syndrome and facial palsy. The pathogenesis and management is discussed.
      All patients made satisfactory recoveries, though with minor residual
      neurological disabilities.

PMID- 9156068
TI  - Sensorineural hearing loss and ulcerative colitis.
AB  - The association of sensorineural hearing loss and ulcerative colitis is well
      documented and it is speculated that this is autoimmune in origin. A case in a 12
      year-old boy is described, that initially responded to steroid therapy, but four
      years later resulted in bilateral, profound sensorineural hearing loss in spite
      of good control of his bowel disease. Immunological tests may provide a clue as
      to the aetiology of suspected cases of autoimmune inner ear disease. Immediate
      treatment with steroids with or without immunosuppressive therapy is essential as
      delay may lead to irreversible hearing loss.

PMID- 9156069
TI  - Sensorineural hearing loss in MELAS syndrome.
AB  - A case of sensorineural hearing loss (SNHL) in MELAS syndrome, a variety of
      mitochondrial cytopathy, is presented. Mitochondrial cytopathies have gone almost
      unreported in the otolaryngology literature, despite evidence from a recent
      review that about 60 per cent of such patients suffer from SNHL (Gold and Rapin,
      1994). The same review revealed that only one of 117 case reports in the period
      1984-1993 contained an audiogram (Swift and Singh, 1988), and none presented
      sequential audiograms. However, audiometry has since been published on 23 members
      of a family with a mitochondrial point mutation causing only sensorineural
      hearing loss with no other symptoms (Vernham et al., 1994). We present a case of
      mitochondrial cytopathy three years after diagnosis with two sequential
      audiograms.

PMID- 9156070
TI  - An unusual complication of T-tubes.
AB  - The morbidity of long-term ventilation tubes (Goode T-tubes) is often discussed
      with reference to otorrhoea, tympanosclerosis and long-term perforation. We
      report three cases of the T-tube slipping into the middle-ear cleft. In two of
      the three patients this was asymptomatic and the T-tubes were left in situ. In
      the third patient this complication was documented on three occasions when the T
      tube was removed and reinserted for recurrent effusions. We are unaware of this
      complication being previously reported in the literature.

PMID- 9156071
TI  - Bilateral otogenic temporal lobe and post-aural abscesses.

PMID- 9156072
TI  - Otolaryngological manifestation of Gorlin Goltz syndrome.
AB  - A 46-year-old Jordanian man was seen in ENT clinic complaining of progressive
      left nasal obstruction and hearing loss for the last five years with a history of
      multiple surgical removal of dental cysts. Clinical and radiological
      investigation revealed a cystic mass occupying the left maxillary sinus
      protruding to the nasal cavity, calcification of the falx cerebri and bifid ribs.
      On these findings Gorlin-Goltz syndrome was confirmed. The case is presented and
      the literature reviewed.

PMID- 9156073
TI  - CT assessment of jugular foramen dominance and its association with hand
      preference.
AB  - Three hundred and seven normal CT scans of the head were prospectively analysed
      to assess jugular foramen dominance. After assessment, hand preference was
      elicited. Of these, 276 were right-handed and 31 were left-handed. Of the right
      handed patients: 180 had a larger jugular foramen on the right; 63 had a larger
      jugular foramen on the left; and in 33 no difference could be discerned. Of the
      left-handed patients: 11 had a larger jugular foramen on the right; 16 had a
      larger jugular foramen on the left; and in four no difference could be discerned.
      The results suggested a significant association between jugular foramen dominance
      and hand preference.

PMID- 9156074
TI  - Mucous membrane plasmacytosis of the upper aerodigestive tract. A case report
      with effective treatment.
AB  - We present a case of plasmacytosis of the mucous membrane of the upper
      aerodigestive tract. This is a rare benign condition characterized by plasma cell
      infiltration of the mucosa, with only nine cases described previously (Ferreiro
      et al., 1994). The lesions, which have a cobblestone appearance, cause throat
      discomfort, dysphonia and mild dyspnoea. All the cases described previously
      failed to respond to antibiotics, systemic steroids, or to surgical resection.
      The present case has however responded favourably to intensive and prolonged
      treatment with beclamethasone oral spray and Corsodyl mouthwashes.

PMID- 9156075
TI  - A hamartoma-like mass on the palate? A possible discussion regarding the
      components of a pigmented naevus and hyperplastic salivary gland.
AB  - An extremely rare mass lesion arising on the hard palate is presented. The
      patient was a 49-year-old Japanese male. He had a painless, semi-globular, smooth
      surfaced and partially pigmented mass located on the left hard palate with no
      evidence of growth for approximately 20 years. The resected specimen included
      hyperplastic salivary gland tissue, nerve fibres and vessels surrounded by
      adipose tissue. All constituent tissues showed excessive growth for this
      location. Also spiralling nests of naevus cells representing inactive
      intramucosal naevus were included. We consider the whole lesion to be a
      hamartoma.

PMID- 9156076
TI  - JLO Travelling Fellowship 1995 report. A visit to Professor Ugo Fisch,
      Universitatspital, Zurich.

PMID- 9156077
TI  - How the neighborhood coherence principle (NCP) can give rise to tissue
      homeostasis: a cellular automaton approach.
AB  - Gap junctional intercellular communication (GJIC) might provide a key mechanism
      for tissue homeostasis. Using a three-dimensional cellular automaton, a model was
      designed to probe the capacity of the particular cell-cell interaction rule known
      as the neighborhood coherence principle (NCP) to produce a control mechanism
      whereby a cell would be told by its neighbors whether or not to enter a division
      cycle. A numerical experiment using this model showed that a potent feedback
      control maintaining a local balance between mitoses, cell differentiation, and
      death emerged from the sequence of cell growth and maturation events. This
      regulation stemmed from the interplay of the juvenile and the senescent fractions
      of a tissue. The regulatory loops shows a variable periodicity which depends on
      the proportion of daughter cells that take the shortcut to re-enter a division
      cycle immediately. A distinctive tissue patchiness, an intrinsic feature of
      systems endowed with the NCP interaction rule, constitutes a predictable feature
      of real cell systems and allows the formulation of empirically testable
      hypotheses about the role of GJIC in growth regulation.

PMID- 9156078
TI  - Does Escherichia coli optimize the economics of the translation process?
AB  - The codon translation rate is usually assumed to be proportional to the cellular
      concentration of the cognate tRNA, but synonymous codons sharing the same cognate
      tRNA may be translated at rather different rates. To account for the latter
      observation, we assume that the translation process is optimized in two respects:
      (i), the codon demand is optimized with respect to the supply of cognate tRNAs
      (composition of the tRNA pool); and (ii), for synonymous codons sharing the same
      cognate tRNA, the usage frequency of each codon correlates optimally with the
      stability of the codon-anticodon complex. These assumptions allow us to compute
      the relative rate constants of synonymous codons. Highly expressed genes, which
      produce 80-90% of the protein mass in the E. coli cell, appear to have selected
      codons which make an optimal use of the tRNA pool. Assuming the optimization
      criteria were valid, a list of codon translation times (in ms) were derived from
      available experimental data.

PMID- 9156079
TI  - Hypothesis testing in evolutionary inference.
AB  - The comparative method, amongst other things, searches for correlations between
      evolutionary variables. These can be used to test null hypotheses. Here I
      consider, in the context of binary variables, the bases of such tests. I examine
      grounds upon which evolutionary traits and events can be regarded as
      statistically independent of each other. I argue that no description of
      observations as independent or non-independent makes sense except in the context
      of a population of possible observations from which they are regarded as having
      being sampled. Significant correlations between traits or changes in traits in
      comparative tests have been taken by some to imply causal links between traits.
      However, the statistical significance of an observed correlation between traits
      is neither necessary nor sufficient for the inference of a causal connection
      between them.

PMID- 9156080
TI  - Derivation of the Tsao-Hanson equation using a statistical thermodynamic method.

PMID- 9156081
TI  - The logic of contrition.
AB  - A highly successful strategy for the Repeated Prisoner's Dilemma is Contrite Tit
      For Tat, which bases its decisions on the "standings" of the two players. This
      strategy is as good as Tit For Tat at invading populations of defectors, and much
      better at overcoming errors in implementation against players who are also using
      it. However, it is vulnerable to errors in perception. In this paper, we discuss
      the merits of Contrite Tit For Tat and compare it with other strategies, like
      Pavlov and the newly-introduced Remorse. We embed these strategies into an eight
      dimensional space of stochastic strategies which we investigate by analytical
      means and numerical simulations. Finally, we show that if one replaces the
      conventions concerning the "standing" by other, even simpler conventions, one
      obtains an evolutionarily stable strategy (called Prudent Pavlov) which is immune
      against both mis-perception and mis-implementation.

PMID- 9156082
TI  - Modelling of phospholipid translocation in the erythrocyte membrane: a combined
      kinetic and thermodynamic approach.
AB  - A mathematical model for the dynamics of transbilayer movements of lipids in the
      erythrocyte plasma membrane is presented. It takes into account an active carrier
      which mediates the ATP-dependent translocation of phosphatidylserine and
      phosphatidylethanolamine from the outer to the cytoplasmic leaflet of the
      membrane and passive fluxes of these lipids as well as of phosphatidylcholine,
      sphingomyelin and cholesterol between both layers. It is assumed that the passive
      fluxes are driven by concentration gradients of the lipids and by mechanical
      forces which result from area limitation for lipid occupation in both leaflets.
      Compared with a previous mathematical treatment of lipid translocation processes
      in the erythrocyte membrane the present model is much closer to realistic
      conditions, e.g. concerning the number of lipid species involved. Furthermore,
      the use of linear flux-force relationships as known from irreversible
      thermodynamics allows a simpler treatment of the passive fluxes than before and
      provides a relevant framework to study the coupling between the various
      processes. The model allows to simulate the time dependent changes of lipid
      concentrations which take place after activation or inhibition of ATP-dependent
      translocation. Using realistic parameter values it explains in quantitative terms
      the stationary asymmetric distribution of lipids under in vivo conditions. Using
      principles of metabolic control analysis we are able to quantify the role of the
      various active and passive processes in determining the asymmetric distribution
      for each lipid species.

PMID- 9156083
TI  - Continuous stability and evolutionary convergence.
AB  - A stochastic process of long-term evolution due to mutation and selection is
      defined over an asexually reproducing population, with selection according to a
      population game with a one-dimensional continuity of pure strategies. Limiting
      the analysis to mutations of small effect, it is shown that long-term dynamic
      stability in such a process is equivalent to continuous stability in the relevant
      population game. In the case of a one-dimensional strategy set (but not
      necessarily if the strategy set is multi-dimensional), this result is virtually
      independent of the distribution of mutations.

PMID- 9156084
TI  - Mathematical model of progressive renal disease.
AB  - A simple mathematical model is proposed that predicts the dynamics of chronic
      progressive renal disease. The model consists of coupled linear differential
      equations formed from three state variables, four control parameters, and three
      parameters related to initial conditions. All have straightforward physical
      interpretations. Applied to a population of nephrons, the model predicted the
      hypertrophic and sclerotic features of parenchyma progressing towards end-stage
      renal disease. Simulation results compared favorably with measurements obtained
      from the literature involving the subtotal nephrectomy rat model for renal
      disease. The time course of disease progression and treatment were considered.
      Also, the implications of the model for designing new diagnostic techniques using
      ultrasonic analysis are discussed.

PMID- 9156086
TI  - A mathematical model to determine the optimal number of fragments for comparison
      of bacterial chromosomic macrorestriction patterns.
AB  - To our knowledge, although comparison of chromosomic macrorestriction patterns
      has become one of the most feasible molecular tools of the current microbial
      taxonomy, a mathematical approach to optimize the choice of a restriction enzyme
      among the endonucleases tested for such comparison has not been previously
      described. The coincidence of restriction patterns for two tested bacterial
      strains with this chosen endonuclease will ensure a high genetic relatedness
      between them. We report a mathematical model to determine the probability of
      hazardously obtaining a particular chromosomic macrorestriction pattern by PFGE
      and to calculate the optimal number of fragments for its comparison. The model
      presented allows us to determine the optimal number of fragments in order to
      compare chromosomic restriction patterns. The model calculates this values as a
      function of the chromosome size and the restriction site length. The model is not
      useful for choosing a restriction enzyme previous to experimental steps, but as a
      tool for the choice of the restriction enzyme that yields the lowest probability
      of hazardously obtaining coincidences of chromosomic patterns. The applicability
      of this model has been exemplified by determining the optimal number of fragments
      for some well-characterized bacteria and by comparing these values with those
      that have been experimentally used.

PMID- 9156085
TI  - H-Y antigen and homosexuality in men.
AB  - In men, sexual orientation correlates with the number of older brothers, each
      additional older brother increasing the odds of homosexuality by approximately
      33%. It is hypothesized that this fraternal birth order effect reflects the
      progressive immunization of some mothers to Y-linked minor histocompatibility
      antigens (H-Y antigen) by each succeeding male fetus, and the concomitantly
      increasing effects of H-Y antibodies on the sexual differentiation of the brain
      in each succeeding male fetus. This hypothesis is consistent with a variety of
      evidence, including the apparent irrelevance of older sisters to the sexual
      orientation of later-born males, the probable involvement of H-Y antigen in the
      development of sex-typical traits, and the detrimental effects of immunization of
      female mice to H-Y antigen on the reproductive performance of subsequent male
      offspring.

PMID- 9156087
TI  - The evolutionary dynamics of selfish replicators: a two-level selection model.
AB  - The aim of the present paper is to study the evolutionary dynamics of selfish
      replicators in a constant genetic background. Selfish replicators are viewed as
      alleles at a single locus, having a pleiotropic effect. Infinitely many alleles
      are possible; they act on individual fitness and have various levels of ability
      to distort segregation. This results in a two-level process of selection,
      including inter-individual selection (effect on individual fitness) and intra
      individual selection (ability to distort segregation). The model takes other
      parameters into account, such as dominance, inbreeding and inbreeding depression.
      The system can have two different behaviours. (1) In some cases, evolutionary
      cycles are possible. The cycles correspond to an alternation of phases with
      predominant inter-individual selection, corresponding to major-effect mutations,
      and phases with predominant intra-individual selection, corresponding to small
      effect mutations. (2) For other values of the parameters, a synthetic fitness can
      be defined: this absolute allelic fitness is estimated as a function of one's
      fitness due to both inter-individual and intra-individual selection. During the
      course of evolution, the synthetic fitness increases. The optimisation of a
      synthetic fitness is the most general process. The optimised value is essentially
      homologous to the value optimised for resource allocation to male and female
      function in hermaphrodites (female function being homologous to the effect on
      individual fitness, and male function being homologous to distortion ability).
      The relative importance of both behaviours is discussed. It is argued that
      repeated sequences causing some human degenerative hereditary diseases may follow
      a two-step evolutionary process: a progressive increase in number of sequences
      accompanied by a decrease of the individual fitness would be followed by massive
      elimination of such sequences. But in general the optimisation of the synthetic
      fitness seems to be more likely.

PMID- 9156088
TI  - Theories of organic amnesia.

PMID- 9156089
TI  - What do theories of the functional deficit(s) underlying amnesia have to explain?

PMID- 9156090
TI  - Implicit memory: what must theories of amnesia explain?
AB  - In their target article on explaining functional deficits in amnesia, Mayes and
      Downes (this issue) discuss the relevance of implicit memory. Our commentary
      considers a number of implicit memory phenomena that may be especially pertinent
      to understanding the functional deficits of amnesia. Recent evidence suggests
      that amnesic patients do not benefit normally from an exact perceptual match of
      stimuli between study and text. We propose that this impairment may reflect one
      manifestation of a more general deficit in associative binding of information
      across different brain subsystems. This idea helps to clarify the distinction
      between implicit and explicit memory, and suggests that studies of implicit
      memory can help to elucidate the functional deficits in amnesia.

PMID- 9156091
TI  - The relationships between temporal lobe and diencephalic structures implicated in
      anterograde amnesia.
AB  - The relationship between the anterograde amnesic syndromes associated with
      diencephalic and temporal lobe pathology is examined in the light of recent
      findings. It is proposed that a common feature of anterograde amnesia is damage
      to part of an "extended hippocampal system" comprising the hippocampus, the
      fornix, the mammillary bodies, and the anterior thalamic nuclei. Damage to this
      system results in deficits in the recall of episodic information, the core
      symptom of anterograde amnesia. In contrast, lesions in this system need not
      disrupt tests of recognition memory when they primarily tax familiarity
      judgements. It is assumed that familiarity judgements depend on other regions
      (e.g. the rhinal cortex in the case of temporal lobe amnesia) and that the
      extended hippocampal system is principally involved in those aspects of
      recognition that are retrieval-based rather than familiarity-based. These
      proposals arise from new evidence on the performance of delayed nonmatching-to
      sample by animals, from a meta-analysis of the performance of amnesic subjects on
      a test of recognition memory, and from new research into the pattern of
      connections between the medial temporal lobe and the medial diencephalon in
      primates.

PMID- 9156092
TI  - Consolidating dispersed neocortical memories: the missing link in amnesia.
AB  - Consolidation is often conceptualised as a general process by which memory traces
      can be strengthened in the brain. An alternative idea, developed here, is that a
      particular sort of consolidation is required for establishing memories belonging
      to a neurobiologically defined category-memories dispersed across multiple
      distinct neocortical zones. These memories are consolidated via the formation of
      a neocortical cell assembly that confers coherence to the set of scattered
      neocortical memory traces. A set of memory traces linked in this manner can
      subsequently serve as the basis for conscious recollection. A disruption of this
      neocortical consolidation process is held to be responsible for the patterns of
      preserved and impaired memory observed in amnesic patients. A suitable strategy
      for empirically testing this sort of theory requires an examination of evidence
      from neuropsychological studies of amnesia and from studies of the neural
      substrates of memory functions in normal subjects.

PMID- 9156093
TI  - A positive approach to viewing processing deficit theories of amnesia.
AB  - This reply is admittedly a defence of the encoding-deficits theory of amnesia.
      However, it attempts to go further by proposing that this deficit, which was
      originally designed just to explain amnesics' explicit episodic memory disorder,
      might be viewed as being but one instance of a more general disorder
      characteristic of all aspects of amnesic patients' information processing. It is
      proposed that amnesic patients' inability to perform more consciously controlled
      conceptual analyses results not only in explicit recall deficits, but sometimes
      also in instances of below normal implicit memory and recognition ability. Their
      ability to perform automatic, perceptual-level processing produces normal
      performance on some implicit and some recognition tasks, but it is not sufficient
      for all tasks.

PMID- 9156094
TI  - How should a database on human amnesia evolve? Comments on Mayes and Downes "What
      do theories of the functional deficit(s) underlying amnesia have to explain?".

PMID- 9156096
TI  - How can be best explain retrograde amnesia in human memory disorder?
AB  - I firstly consider general issues relating to our attempts to understand
      retrograde amnesia. Three main hypotheses are reviewed that have been proposed to
      account for retrograde amnesia. A theory is outlined to explain the dense
      autobiographical amnesia that is a focal phenomenon in some cases of severe head
      injury. This theory postulates that autobiographical retrieval requires the
      activation of a distributed network of cognitive operations, and that
      autobiographical amnesia results from the occurrence of multiple areas of
      pathology, distributed over both space and time.

PMID- 9156097
TI  - Memory for items and memory for relations in the procedural/declarative memory
      framework.
AB  - A major area of research in memory and amnesia concerns the item specificity of
      implicit memory. In this paper we address several issues about the nature of
      implicit memory phenomena and about what constitutes an "item", using the
      procedural/declarative memory theory to guide us. We consider the nature of
      memory for items and of memory for relations among items, within the context of
      the procedural/declarative framework, providing us with the foundation necessary
      to analyse the basis for item-specific implicit memory phenomena. We review
      recent work from our laboratories demonstrating the fundamentally relational and
      flexible nature of declarative memory representation, in both humans and animals,
      and the essential role of the hippocampal system in relational memory processing.
      We show, further, that the memory representations supporting implicit memory
      phenomena are inflexible and nonrelational, and are tied to specific processing
      modules. Finally, we introduce empirical approaches that blur the distinction
      between skill learning and repetition priming, and show computational modelling
      results that demonstrate how these two implicit memory phenomena can be mediated
      by a single incremental learning mechanism, in accord with the claims of the
      procedural-declarative theory. Taken together, these various analyses of memory
      for items and memory for relations help to illuminate the nature of the
      functional deficit in amnesia and the memory systems of the brain.

PMID- 9156098
TI  - Extending models of hippocampal function in animal conditioning to human amnesia.
AB  - Although most analyses of amnesia have focused on the loss of explicit
      declarative and episodic memories following hippocampal-region damage,
      considerable insights into amnesia can also be realised by studying hippocampal
      function in simple procedural, or habit-based, associative learning tasks.
      Although many simple forms of associative learning are unimpaired by hippocampal
      damage, more complex tasks which require sensitivity to unreinforced stimuli,
      configurations of multiple stimuli, or contextual information are impaired by
      hippocampal damage. In several recent papers we have developed a computational
      theory of hippocampal function which argues that this brain region plays a
      critical role in the formation of new stimulus representations during learning
      (Gluck & Myers, 1993, 1995; Myers & Gluck, 1996; Myers, Gluck, & Granger, 1995).
      We have applied this theory to a broad range of empirical data from studies of
      classical conditioning in both intact and hippocampal-lesioned animals, and the
      model correctly accounts for these data. The classical conditioning paradigm can
      be adapted for use in humans, and similar results for acquisition are obtained in
      both normal and hippocampal-damaged humans. More recently, we have begun to
      address an important set of category learning studies in both normals and
      hippocampal-damaged amnesics. This work integrates experimental studies of
      amnesic category learning (Knowlton, Squire, & Gluck, 1994) with theoretical
      accounts of associative learning, and builds on previously established
      behavioural correspondences between animal conditioning and human category
      learning (Gluck & Bower, 1988a). Our work to date illustrates some initial
      progress towards a more integrative understanding of hippocampal function in both
      animal and human learning, which may be useful in guiding further empirical and
      theoretical research in human memory and amnesia.

PMID- 9156099
TI  - Implicit and explicit memory in amnesia: some explanations and predictions by the
      TraceLink model.
AB  - After a brief overview of some of the characteristics and neuroanatomy of
      amnesia, a new model of amnesia is described: the TraceLink model. One novel
      aspect of the model is that it makes specific and testable predictions regarding
      semantic dementia, a recently described disorder that is viewed here as being
      related to amnesia. The TraceLink model consists of: a trace system (roughly the
      neocortix), a link system (hippocampus and adjacent areas), and a modulatory
      system (certain basal forebrain nuclei). Different forms of learning in the
      TraceLink model are explained, followed by a discussion of implicit and explicit
      memory, prominence (ease of recall) and persistence (resistance to brain damage),
      consolidation, and Ribot gradients in retrograde amnesia. Patterns of recovery
      from retrograde amnesia are also discussed, and novel predictions are derived
      regarding implicit memory and various forms of amnesia.

PMID- 9156100
TI  - Predicting syndromes of amnesia from a composite holographic associative
      recall/recognition model (CHARM).
AB  - The composite holographic associative recall/recognition model (CHARM) is used to
      predict the amnesia syndromes that are expected under conditions of discrete
      lesions to different components of the model. The components that are needed to
      allow recognition, recall, and rehearsal are: (1) perceptual/lexical processing
      and pattern identification, (2) consciousness or working memory, (3) association
      formation, (4) composite storage, (5) novelty monitoring and control, and (6)
      retrieval. Deficits in each of these components will have specific effects on
      memory, generating characteristic profiles of performance. Comparison of the
      profiles exhibited by patients to the component-based profiles predicted by the
      model identify the component impaired in a given patient, and connect the memory
      impairments to the underlying infarcted brain structures. The model, thus,
      relates the memory tasks to the particular memory components that allow enactment
      of those tasks, and shows how the dysfunction of particular components produces
      specific impairments.

PMID- 9156101
TI  - New approaches to the study of amnesic patients: what can a neurofunctional
      philosophy and neural network methods offer?
AB  - In this paper I first consider a neurofunctional approach to the study of amnesic
      patients. This approach stresses the need for theorising about the processing
      operations of brain regions and circuits rather than for theorising about
      neuropsychological syndromes. A syndrome such as amnesia-may not exist, in any
      meaningful sense, if there is marked heterogeneity within the patients grouped
      together in this way. Powerful neuroimaging techniques may now allow a more
      useful basis for grouping patients in terms of lesion location rather than
      aetiology. In turn this will allow an evaluation of the information processing
      functions subserved by the lesioned structures. The second strand to the present
      paper stresses the weakness in the specification of current theories. This has
      made it difficult to select experimental tasks that decisively measure the key
      components of those theories. The paper makes the case that explicit neural
      network models are a useful way to try to overcome this problem. In line with
      these ideas, the paper begins to build a model of how the brain may achieve
      useful kinds of stimulus representations. Considerations of human behaviour in
      category learning tasks have emphasised parallel and interacting roles for both
      exemplar- and element-based stimulus representations. It is suggested that the
      hippocampus itself may encode exemplar representations, and these may provide a
      basis for episodic memory as well as some types of category learning. It is
      further suggested that the ventral striatum may encode the element-based
      representations. The model allows some new and detailed predictions for the
      performance of amnesic subjects related to lesion location.

PMID- 9156102
TI  - Concluding comments: common themes, disagreements, and future directions.

PMID- 9156103
TI  - Quality of life: the main outcome measure of palliative care.

PMID- 9156104
TI  - A comparison of hospice and hospital care for people who die: views of the
      surviving spouse.
AB  - To compare the quality of inpatient care for dying people in St Christopher's
      Hospice, London and nearby hospitals in 1994 and make comparisons with earlier
      studies of the same setting, interviews were undertaken with spouses of people
      who had died from cancer in these settings, matched by age and sex. The subjects
      comprised 66 people who had died in 1994, 33 of whom had died in the hospice, 33
      in local hospitals. The mean age was 70.2, 61% were male. The hospice group were
      more likely to know that they were dying and less likely to be admitted as
      emergencies. Treatment for pain, breathlessness and nausea from both sources
      provided relief in almost all cases. Most information about the illness was given
      by hospital doctors before hospice care occurred. Where it occurred,
      communication by hospice staff was judged better than that by hospital doctors.
      Staff in hospitals were more likely to be judged 'very busy'. Hospice respondents
      were less likely to want improvements, and more likely to judge the institution
      as being 'like a family'. Earlier studies had shown a trend for symptom control
      to have improved in hospitals but for difference in the psychosocial climate to
      favour the hospice, By 1994, this latter difference was still obtained. We stress
      the role of hospital staff and general practitioners in helping patients accept a
      terminal prognosis, so that better-planned care can proceed. The busy public
      atmosphere of some hospital wards may not be conducive to the good care of dying
      people.

PMID- 9156105
TI  - A comparison of hospice and hospital care for the spouses of people who die.
AB  - To compare the quality of care for spouses of dying people in St Christopher's
      Hospice, London and nearby hospitals in 1994 and to make comparisons with earlier
      studies of the same setting, interviews were undertaken with spouses of people
      who had died from cancer in these settings, matched by the deceased's age and
      sex. The subjects comprised 66 people whose spouses had died in 1994, 33 of whom
      had died in the hospice, 33 in local hospitals. The mean age was 69.3; 61% were
      female. No significant differences between groups were found on the outcome
      measures (adjustment to bereavement, anxiety and psychosomatic symptoms at the
      time of the final admission), largely replicating earlier studies in the same
      setting. In various respects hospitals have moved closer to hospice practice: in
      contrast to earlier studies, there were no differences in visiting patterns or in
      spouses helping with inpatient care. Bereavement follow-up is now initiated in
      some cases by hospitals. Liberal visiting hours could be stressful, however, and
      spouses sometimes helped with care to remedy staff shortcomings. Regret at not
      being present at the death was more common in the hospital group. Bereavement
      interventions may have more effect on subsequent adjustment if targeted on high
      risk individuals. Other benefits than adjustment, however, may be achievable.
      Steps to create a calm atmosphere on hospital wards where people can be with
      their relatives near the time of death are desirable.

PMID- 9156106
TI  - The effects of the clinical characteristics of dying cancer patients on informal
      caregivers' satisfaction with palliative care.
AB  - To assess associations between informal caregivers' satisfaction with services
      delivered to their dying cancer patients and their perceptions of the duration of
      functional limitation and the duration of various symptoms experienced by these
      patients, a secondary analysis was conducted on a subsample of the Regional Study
      of Care for the Dying (RSCD). The RSCD is a retrospective interview survey of
      family members or others who knew about the last year of life of a random sample
      of people who died in 20 health districts in the UK in 1990. The subsample
      consisted of 1858 informal caregivers of people who died from cancer (ICD codes
      140-208). More than half (52%) of informal caregivers were highly satisfied with
      community nurses, compared to 39% and 35% of those who reported high satisfaction
      with services provided by general practitioners and hospital doctors
      respectively. Informal caregivers of patients who died from a lymphatic or
      haematopoietic tissue cancer were more likely than others to report high
      satisfaction with hospital doctors (47%), while least satisfaction was reported
      by those who cared for patients who had a neoplasm of the genito-urinary or
      respiratory/intrathoracic organs (30%). The duration of pain was not
      significantly related to any of the satisfaction measures. The results suggest
      the need to take patient clinical characteristics into account in population
      based evaluations of palliative care. They also indicate the need for more
      research to be carried out to assess the reasons behind the dissatisfaction of
      informal caregivers of patients with respiratory or genito-urinary cancers with
      services provided by hospital doctors and to detect whether these patients have
      unmet needs that should be addressed. More research is also needed into the
      management of symptoms by the general practitioners, especially symptoms
      pertaining to respiration and incontinence.

PMID- 9156107
TI  - Attitudes and views of physicians and nurses towards cancer patients dying at
      home.
AB  - The objective was to study attitudes and views of primary care professionals
      towards terminally ill cancer patients who die at home, using a cross-sectional
      study based in the health district of Manresa (province of Barcelona, Catalonia,
      Spain) of the Catalan Health Service, involving 151 primary health care
      professionals (87 physicians and 64 nurses). By using a self-responded anonymous
      questionnaire (response rate 89%) it was found that despite excellent motivation,
      primary care professionals reported widespread frustration and a poor opinion of
      the quality of care provided to terminally ill cancer patients. Attitudes and
      views clearly differ by age, sex and geographic setting. In the study area, most
      professional are reluctant to disclose the diagnosis of cancer, and this attitude
      is associated with a more favourable assessment of the support provided to the
      family. The idea that the most appropriate place of death is at home is strongly
      linked to the belief that patients ought to be informed of their illness, to
      feelings of frustration and to youth. These findings further substantiate the
      need and the potential for ample changes in terminal cancer care in Spain.

PMID- 9156108
TI  - Dysgraphia and terminal delirium.
AB  - Delirium is a frequently encountered clinical condition in palliative medicine,
      but it is often unrecognized and misdiagnosed. The cardinal sign of delirium is
      that of impaired consciousness. Writing skills are reported to be a delicate
      indicator of consciousness impairment, and a too infrequently utilized clinical
      sign of delirium. Ten delirious hospice patients completed the Frenchay Aphasia
      Screening Test which showed that writing was the most impaired of the language
      dysfunctions assessed. The simple clinical task of a request to write 'name and
      address' revealed overt dysgraphic errors among delirious patients. This
      examination is clinically acceptable to hospice practice and may be an adequate
      and accurate bedside test of delirium.

PMID- 9156109
TI  - Schooling as a part of palliative care in paediatric oncology.
AB  - For children with incurable life-threatening diseases, social reintegration is an
      illusion. Schooling for these children is both possible and desirable, but its
      specific objectives must be adapted. The educational career of 30 French school
      children with incurable cancer was followed. Data concerning the children's
      degree of motivation to attend school and its evolution during the course of the
      disease as well as the measures adopted to maintain school attendance were
      analysed. Sixty per cent of the children demonstrated a genuine desire to attend
      school until the advanced stages of their disease. Reading, mathematics and
      computer work were their favourite subjects, increasing physical disability and
      fatigue diminished their motivation over time. Refusal to attend school occurred
      in 40% of the children, who had either extracurricular interests or poorly
      controlled pain. School attendance for the terminally ill child's part of
      palliative care and has specific medical and educational goals. As such, its
      objectives are quite distinct from those of other educational reintegration
      projects proposed for children with cancer.

PMID- 9156110
TI  - A comparison of the use of sedatives in a hospital support team and in a hospice.
AB  - This study examines how frequently and for what indications sedatives are
      prescribed in a hospital support team and in a hospice. We also looked at the
      survival of sedated patients from the date of admission and from the start of
      sedation. Overall 26% of patients were prescribed sedatives in order to sedate
      them (31% at the hospice and 21% at the hospital) and 43% of patients were given
      sedatives for symptom control (67% at the hospice and 21% at the hospital).
      Sedated patients survived for a mean of 1.3 days after the start of sedation, and
      there was no detectable difference in survival from the date of admission between
      sedated and nonsedated patients.

PMID- 9156111
TI  - An analytical study of the changing health of a hospice population 1978-89.
AB  - This study explores the changing characteristics of patients admitted to Sir
      Michael Sobell House, Oxford, between 1978-89. These dates represent the period
      between the first available records and the first computerized records. Analysis
      is between these dates and has been undertaken to enable future comparison
      between the early life of the unit with more recent developments. Using secondary
      sources the following areas were compared statistically: information related to
      general characteristics such as sex and age; information related to referral such
      as the number of referrals; diagnosis on referral and reasons for referral;
      information related to problems presented and place of death. Significant
      findings included an increase in referrals and patient survival; an increase in
      patients dying at home; a decrease in symptoms presented on referral and fewer
      referrals for terminal care; and an increase in referral for rehabilitation,
      assessment and support. Reasons for these changes are suggested.

PMID- 9156112
TI  - HIV infection: the spectrum of symptoms and disease in male and female patients
      attending a London hospice.
AB  - To delineate the demographic features and clinical profile of male and female
      individuals utilizing a respite, rehabilitation and hospice centre in London, a
      retrospective study of patient notes was undertaken. The subjects were 59 male
      and 59 female HIV patients at first admission to the hospice. The study revealed
      clinically important differences between men and women and also identified
      special problems for African women and intravenous drug users. Women experienced
      more constipation, headache and musculoskeletal pain than men. Men suffered more
      neuropathic pain and visual loss. Lower respiratory tract infections were more
      common in women, especially in those with a history of injection drug use.
      Gynaecological morbidity was common. There was no difference in AIDS diagnoses
      between men and women. HIV encephalopathy developed in 23% of the cohort during
      the follow-up period which has implications for provider units. There are
      increasing numbers of HIV-positive women and injection drug users being referred
      for palliative care services. Multidisciplinary teams should be aware of the
      particular symptom profile of these groups.

PMID- 9156113
TI  - What is qualitative research and what can it contribute to palliative care?

PMID- 9156114
TI  - Palliative medicine at the crossroads.

PMID- 9156115
TI  - Psychosocial support in an outpatient clinic.

PMID- 9156116
TI  - Diminished effect of transdermal fentanyl in the terminal phase?

PMID- 9156117
TI  - Problems of sweating and transdermal fentanyl.

PMID- 9156118
TI  - The language of breathlessness.

PMID- 9156119
TI  - What's in a name? The classification of common headaches.

PMID- 9156120
TI  - The management of congestive heart failure.
AB  - Despite the remarkable advances in cardiovascular therapeutics over the past four
      decades, little impact has been made on either the incidence or mortality rate of
      congestive heart failure and it remains a major clinical and public health
      problem. Recent practice audits have suggested that proven efficacious therapies
      are not maximally applied in patients with this condition. An approach to the
      patient with congestive heart failure is presented, emphasizing the two distinct
      syndromes of systolic dysfunction and diastolic dysfunction. Treatment
      recommendations are derived from consideration of the underlying pathophysiology
      and the evidence from randomised clinical trials.

PMID- 9156121
TI  - Haemophilia.
AB  - Although the nature of haemophilia has been understood for thousands of years,
      knowledge of its molecular genetics is recent. These X-linked bleeding disorders
      have diverse underlying DNA defects and, in 1992, DNA inversion within the X
      chromosome was found to explain half of the most serious cases of haemophilia A.
      The life-span and quality-of-life for patients with haemophilia had improved
      steadily throughout the early 1980s but the principal cause of death remained
      intracranial haemorrhage until the epidemic of HIV infection due to contaminated
      factor concentrates. Infection with hepatitis C virus is almost universal for
      patients treated with clotting factors before 1985. No curative treatment is
      available for hepatitis C at present. Knowledge of the transmission of viruses in
      concentrates has led to important developments in processing techniques to
      eliminate them. Recombinant technology has produced factor VIII and, more
      recently, factor IX concentrate which is likely to be very safe. Development of
      inhibitors to factor concentrates (especially factor VIII) remains one of the
      most serious complications of haemophilia. The variety of treatments available
      testifies to the lack of a single universally efficacious one. The use of
      prophylactic treatment has been conclusively demonstrated to result in a
      preservation of joint function in severely affected patients who might otherwise
      develop significant joint problems. The many facets of the care of patients with
      severe haemophilia, ranging from dental care to genetic counselling, can be
      advantageously co-ordinated in a haemophilia comprehensive care centre.

PMID- 9156122
TI  - Carcinoid tumours.
AB  - The use of long-acting and potent somatostatin analogues is a major advance in
      the management of carcinoid tumours. In addition to providing effective symptom
      relief in malignant carcinoid syndrome, octreotide can also be used for
      diagnostic purposes. Despite its expense, octreotide is the current agent of
      choice for the treatment of this condition while analogues with different
      receptor specificities and pharmacokinetics hold promise for the future. Gastric
      carcinoids have aroused interest because of their experimental association with
      chronic hypergastrinaemia, a condition now commonplace because of the widespread
      use of H2-blockers and proton-pump inhibitors. This subject is reviewed. The slow
      evolution of many tumours demands prolonged follow-up and the active use of a
      variety of palliative interventions. These include measures such as hepatic and
      cardiac surgery, which might be deemed inappropriate for patients with other
      types of metastatic malignancy. Interferons may have a role when first-line
      treatments have failed. Chemotherapy is, generally, of limited value.

PMID- 9156124
TI  - Pneumococcal vaccine.
AB  - Streptococcus pneumoniae is a frequent cause of pneumonia and meningitis. This
      article looks at the pneumococcal vaccine, its uses, efficacy, and adverse
      effects and how vaccination may be improved. We also look at the role of the new
      conjugate vaccines.

PMID- 9156123
TI  - Haemopoietic growth factors.
AB  - Haemopoietic growth factors are involved in the production of the various blood
      cells from progenitors in the bone marrow, making them useful in a range of
      clinical situations. The genes for several of them have been cloned and their
      production engineered by recombinant technology, making them widely available.
      Myeloid growth factors are used to support patients in the aftermath of
      chemotherapy and bone marrow transplantation and have potential application in
      the treatment of infectious diseases. Erythropoietin is widely used for patients
      with anaemia due to failure of marrow production, having established its
      effectiveness in chronic renal failure. Thrombopoietin has recently been
      described and may provide a means to alleviate thrombocytopenia. Current
      indications and areas of recent reappraisal are addressed in this review.

PMID- 9156125
TI  - Prognosis and management of Crohn's disease in the over-55 age group.
AB  - The course, prognosis and management of 62 patients with Crohn's disease aged 55
      years or over at diagnosis has been reviewed. The distal ileus was the commonest
      site of disease in the older patient, where the characteristic presentation was
      acute after initially mild symptoms. Early local resection was often required,
      particularly where there was diagnostic doubt or suspicion of caecal malignancy.
      Recurrence rates were much lower in the older patient than after resection in
      younger patients. Medical treatment played a minor role in the management of
      patients with distal ileal disease, in part because stricture formation was
      present at diagnosis and the acute nature of symptoms at presentation led to
      early surgical treatment. Colonic Crohn's disease was usually confined to the
      distal or left side of the colon and initially could be difficult to distinguish
      from diverticular disease. Extensive colonic Crohn's disease was rare. The
      apparently limited disease was not necessarily associated with a good prognosis,
      since disease at this site sometimes progressed rapidly, necessitating urgent
      surgical resection. Medical treatment (corticosteriod therapy, with or without
      azathioprine) was usually effective initially for treatment of symptomatic
      colonic Crohn's disease, but sustained remission was rare. Those patients with
      persistent symptoms were restored to good health with surgical treatment but at a
      price, in that nearly half eventually required a permanent stoma.

PMID- 9156127
TI  - Unsuspected thyrotoxicosis and hyperemesis gravidarum in Asian women.
AB  - This report describes three women with hyperemesis gravidarum caused by
      previously undiagnosed thyrotoxicosis. All three women were eight weeks pregnant
      and only one woman had typical features of thyrotoxicosis. Hyperemesis could not
      be controlled by anti-emetics. The patients were successfully treated with
      antithyroid drugs. Anti-thyroid treatment does not need to be continued once
      resolution of symptoms and thyrotoxicosis have occurred.

PMID- 9156126
TI  - The significance of arterial hypertension at the onset of clinical lupus
      nephritis.
AB  - The prognostic importance of hypertension at the onset of clinical lupus
      nephritis is not well established. We studied retrospectively 44 patients with
      lupus nephritis in order to ascertain the prevalence of hypertension at
      presentation and to investigate a possible association between hypertension and
      renal functional impairment. A correlation was also sought between hypertension
      and histological class of lupus nephritis. Hypertension was graded as mild
      (diastolic 95-99 mmHg), moderate (100-114) or severe (> 115). Impaired renal
      function (creatinine > 120 mumol/l) was graded as mild (120-200 mumol/l),
      moderate (200-350 mumol/l), or severe (> 350 mumol/l). Histological class and the
      presence of hypertensive renal vascular lesions was recorded. The prevalence of
      hypertension was 38%. There were 17 hypertensives and 27 normotensives. The
      incidence of renal impairment was greater in the hypertensives, 47% vs 18.5% (p =
      0.04). Mean serum creatinine was also higher higher in this group (p = 0.02). The
      presence of hypertensive renal vascular lesions identified a high-risk subgroup
      who had a higher incidence of renal functional impairment and worse renal
      function than the hypertensive group as a whole. Even at an early stage,
      hypertension and hypertensive renal vascular lesions correlated well with renal
      functional impairment. Aggressive treatment of hypertension is therefore
      essential in early lupus nephritis in order to prevent further deterioration of
      renal function as the disease evolves.

PMID- 9156129
TI  - Supervised drug administration in patients with refractory hypertension unmasking
      noncompliance.
AB  - Noncompliance with medication is common, particularly in asymptomatic conditions
      such as hypertension that require long-term treatment, and is often unsuspected.
      We describe two patients with refractory hypertension in whom noncompliance was
      confirmed by a precipitous fall in blood pressure when antihypertensive
      medications were given under direct supervision.

PMID- 9156128
TI  - Acute fulminant neuropathy in a patient with Churg-Strauss syndrome.
AB  - We report a patient with an acute neuropathy initially mimicking Guillain-Barre
      syndrome, both clinically and electrophysiologically. Persistent eosinophilia,
      positive antineutrophil cytoplasmic antibody and eosinophilic vasculitis in sural
      nerve biopsy later confirmed Churg-Strauss syndrome. Since vasculitic neuropathy
      can present in an acute and fulminant form, the role of early antibody testing
      and sural nerve biopsy in atypical cases of acute neuropathy is emphasized.

PMID- 9156130
TI  - Painless stress fractures in diabetic neuropathic feet.
AB  - We describe two patients with diabetes mellitus and associated neuropathy, who
      presented with painless foot swelling and no history of trauma. X-Rays revealed
      recent underlying fractures-in one of a metatarsus, and the other of a proximal
      phalanx. These were assumed to be 'stress' fractures unassociated with pain
      because of the severe sensory neuropathy. Though spontaneous fractures in
      neuropathic feet have been previously described, they almost always occur in
      association with Charcot joints, and are usually painful. The differential
      diagnosis of acute swelling in the foot of a diabetic patient with sensory
      neuropathy should include stress fracture.

PMID- 9156131
TI  - A case of plastikophagia.

PMID- 9156132
TI  - Pulmonary infiltrates and skin lesions.

PMID- 9156133
TI  - Vomiting and weight loss.

PMID- 9156134
TI  - Arrhythmia in a 38-year-old man.

PMID- 9156135
TI  - Cerebrovascular accident in a 77-year-old man.

PMID- 9156136
TI  - Hereditary essential tremor and restless legs syndrome.

PMID- 9156137
TI  - Hookworms to treat haemachromatosis?

PMID- 9156138
TI  - Obtaining the correct drug history.

PMID- 9156139
TI  - Incarceration of the penis by a metallic ring.

PMID- 9156140
TI  - Limitations and promise in the diagnosis and treatment of obstructive sleep
      apnoea.

PMID- 9156141
TI  - Aetiology of pneumonia following isolated closed head injury.
AB  - Patients undergoing mechanical ventilation (MV) after an isolated closed head
      injury (ICHI) have often been found to develop hospital-acquired pneumonia (HAP)
      well before subjects who require MV for different reasons. In a prospective study
      of patients receiving MV after an ICHI. 38 subjects (out of 65 with clinically
      suspected HAP) had a bacteriological diagnosis established on the basis of
      correspondence between cultures made from bronchoalveolar lavage and protected
      specimen brush (with quantitative thresholds of 10(4) and 10(3) cfu ml-1,
      respectively). Patients were separated according to the time of onset of HAP,
      with 20 subjects who developed HAP within 4 days of the start of MV (early onset
      pneumonia, EOP) and 18 subjects who developed HAP after the fourth day (late
      onset pneumonia, LOP). In those who had LOP, an expected spectrum of organisms
      was found, with Gram-negatives (especially Pseudomonas sp.) accounting for the
      majority of isolates. However, in EOP cases, Gram-positive bacteria (especially
      Staphylococcus sp. and Streptococcus pneumoniae) were found to largely
      predominate (P = 0.0000026). This confirms the high incidence of staphylococcal
      pneumonia in neurosurgery patients, and also provides evidence that the vast
      majority of such staphylococcal pneumonia are EOP. Unlike most previous reports,
      the microbiological findings from the present study suggest that a cut-off point
      of 4 days successfully distinguishes between EOP and LOP. Since these two
      clinical entities differ significantly in terms of pathogenesis and aetiology,
      preventive measures and therapeutical protocols have to be tailored accordingly.

PMID- 9156142
TI  - Rapid detection of pneumococcal antigen in lung aspirates: comparison with
      culture and PCR technique.
AB  - Detection of pneumococcal antigen has been used to increase the rate of diagnosis
      of pneumococcal pneumonia. The present study was designed to determine the value
      of rapid detection of pneumococcal antigen in samples obtained by transthoracic
      needle aspiration (TNA) from patients with community-acquired pneumonia (CAP) in
      a comparative analysis with culture and polymerase chain reaction (PCR).
      Pneumococcal antigen was detected by latex agglutination. One hundred and ten
      consecutive patients diagnosed with CAP underwent TNA. Patients were grouped,
      according to PCR, culture and serological results, into pneumococcal pneumonia (n
      = 18), other known aetiology (n = 67) and unknown aetiology (n = 25). In patients
      with pneumococcal pneumonia, antigen was detected in 17 (94.4%) cases. Antigen
      was detected in one and nine patients with pneumonia of other known or unknown
      aetiologies, respectively, yielding a specificity of 89.1%. In conclusion,
      detection of pneumococcal antigen on samples obtained by TNA from patients with
      CAP provides a sensitive and specific diagnosis of Streptococcus pneumoniae
      infection. Furthermore, its rapid results would reduce the dependence on
      empirical treatments.

PMID- 9156143
TI  - Intensive care management of varicella pneumonia.
AB  - To determine the clinical features, treatment and outcome of severe varicella
      pneumonia with hypoxic respiratory failure requiring intensive care management, a
      prospective survey of consecutive cases was undertaken. Fifteen consecutive adult
      cases of varicella pneumonia with respiratory failure admitted to a 10-bed
      respiratory intensive care unit over a period of 10 y from 1984-1993 were
      studied. All patients were given acyclovir immediately on admission. The level of
      ventilatory support needed was determined by the severity of gas exchange
      abnormality, and varied from face mask oxygen (three patients), through
      continuous positive airway pressure (CPAP) by face mask (eight patients), to
      continuous positive pressure ventilation (CPPV) (four patients). The majority of
      patients were young females, only one of whom was pregnant. All patients had been
      in close contact with a known case of chickenpox. All patients responded well to
      acyclovir and ventilatory support with improved oxygenation. Monitoring with
      pulse oximetry was important to detect episodes of desaturation on inadvertent
      discontinuation of positive and expiratory pressure (PEEP). Two patients were
      admitted with bacterial superinfection, and one patient, who had required
      intubation and CPPV, developed nosocomial respiratory tract infection. There were
      no deaths. This experience suggests that intensive care admission, with the early
      administration of intravenous acyclovir and recognition of the severity of the
      hypoxaemia resulting from varicella pneumonia (which can be reversed with PEEP),
      should reduce the mortality of severe varicella pneumonia in adults.

PMID- 9156144
TI  - Allergic bronchopulmonary aspergillosis: the spectrum of computed tomography
      appearances.
AB  - Although computed tomography (CT) of the thorax has been compared to plain chest
      radiography and bronchography for demonstration of central bronchiectasis (CB) in
      allergic bronchopulmonary aspergillosis (ABPA), the CT presentation of the
      disease is yet to be highlighted. With this in view, the CT appearances in 23
      patients with ABPA were evaluated. The scans were assessed for bronchial,
      parenchymal and pleural abnormalities. Central bronchiectasis was identified in
      all patients, involving 114 (85%) of the 134 lobes and 210 (52%) of the 406
      segments studied. Other bronchial abnormalities such as dilated and totally
      occluded bronchi (11 patients), air-fluid levels within dilated bronchi (five
      patients), bronchial wall thickening (10 patients) and parallel-line shadows
      (seven patients) were also observed. Parenchymal abnormalities, which had a
      predilection for upper lobes, included consolidation in 10 (43%) patients,
      collapse in four (17%) patients and parenchymal scarring in 19 (83%) patients. A
      total of six cavities were seen in three (13%) patients, and an emphysematous
      bullae was detected in one (4%) patient. The pleura was involved in 10 (43%)
      patients. Ipsilateral pleural effusion with collapse was observed in one patient,
      while in nine other patients, parenchymal, lesions extended up to the pleura.
      Concomitant allergic Aspergillus sinusitis (AAS) was also detected in three (13%)
      of the 23 patients. Computed tomography of the thorax in patients with ABPA
      provides a sensitive method for the assessment of bronchial, parenchymal and
      pleural abnormalities, and should constitute a part of the diagnostic work of the
      disease.

PMID- 9156145
TI  - Effects of smoking and clinical status on lung function in human immunodeficiency
      virus (HIV)-seropositive subjects.
AB  - Lung function was measured at 3-month intervals for up to 1 yr in a group of
      Caucasian HIV-seropositive subjects. The objective was to document any
      deterioration in lung function and seek correlations between such deterioration
      and smoking history and Centers for Disease Control (CDC) status. Ninety-nine
      subjects were studied at enrollment; 43 were followed-up (mean duration 9 +/- 3
      months). Ninety-five of the 99 enrolled subjects remained free of HIV-related
      respiratory disease and were included in the analysis. At enrollment, carbon
      monoxide diffusing capacity (TLCO) was significantly lower than predicted in non
      smokers, smokers and ex-smokers (88, 77 and 88%, respectively, P < 0.001). The
      TLCO measurements in the smoking group were significantly lower than those of the
      life-long non-smoking subjects (P < 0.01). Residual volume (RV) was significantly
      higher than predicted in smokers (111%, P = 0.02). During follow-up, all three
      groups demonstrated significant declines in TLCO (7%, P = 0.01; 9%, P = 0.005;
      13%, P < 0.001, respectively), and increases in RV (9%, P = 0.03; 13.5%, P =
      0.02, 22%, P = 0.02, respectively). At enrollment, significantly lower than
      predicted values of TLCO were observed in groups stratified by CDC criteria: in
      asymptomatic HIV-seropositive subjects (CDC 11) 89%, P = 0.01; persistent
      generalized lymphadenopathy (PGL) 84%; AIDS-related complex (ARC) 81%; and in non
      pulmonary AIDS (IV C1) 69%, P = 0.0001, respectively. Residual volume was
      significantly higher than predicted in CDC II (114%, P = 0.05). During follow-up,
      TLCO fell in groups PGL and ARC by 7 and 9%, respectively, while RV increased in
      groups CDC II, PGL and ARC by 17, 15 and 8%, respectively. Only the TLCO decline
      in PGL showed any linkage to clinical deterioration. This study demonstrates
      deficits at enrollment, and a continuing decline of TLCO and increase in RV in
      HIV-seropositive subjects without overt lung disease.

PMID- 9156147
TI  - Metastatic large cell lung cancer presenting with numb chin syndrome.
AB  - The numb chin syndrome is an uncommon occurrence with cancer and consists of
      numbness in the area of distribution of the mental nerve. Most cases of this
      syndrome occur in the presence of underlying breast cancer or lymphoma with
      survival measured in months once this syndrome is manifest. Reported below is the
      case of a man with metastatic large cell lung cancer whose presenting complaint
      was chin and lip numbness.

PMID- 9156146
TI  - An assessment of steroid hypersensitivity in asthma.
AB  - In dermatological practice, allergy to topical corticosteroids used to treat
      eczema is a recognized and common event. The typical presentation is of an eczema
      which fails to improve or deteriorates with treatment. Topical corticosteroids
      are also used to treat mucosal disease. This study assesses allergy to inhaled
      corticosteroids in asthmatics. In the patient group selected, there was no
      evidence of relevant corticosteroid allergy.

PMID- 9156148
TI  - Elevated serum angiotensin converting enzyme levels in metastatic ovarian
      dysgerminoma.
AB  - A case of a 32-year-old XY genotype female is described, presenting with
      mediastinal and abdominal lymphadenopathy and associated with an elevated serum
      angiotensin I converting enzyme (SACE) level. Lymph node histology showed a
      malignant dysgerminoma of ovarian origin. Combined chemotherapy led to a
      radiological regression of the lymphadenopathy and coincided with a decrease in
      SACE concentration. The authors suggest that SACE may be a marker for
      disseminated germinoma tumours and may be useful for monitoring treatment.

PMID- 9156149
TI  - Bronchiolitis obliterans organizing pneumonia after adjuvant radiotherapy for
      breast carcinoma.

PMID- 9156150
TI  - Endobronchial metastasis from rectal adenocarcinoma.
AB  - A case of endobronchial metastasis 2 yr following treatment of rectal carcinoma
      is presented. Endobronchial metastases from extrathoracic primary malignancies
      are uncommon, the estimated frequency and possible mechanisms underlying this
      complication are discussed. The importance of recognizing possible endobronchial
      metastasis is in the approach to management and prognosis.

PMID- 9156152
TI  - Cancer in the 21st century.

PMID- 9156151
TI  - Passive smoking: a little inspiration can seriously damage health.

PMID- 9156153
TI  - Cot death--progress at last?

PMID- 9156154
TI  - John Coakley Lettsom and "the highest and most divine profession, that can engage
      human intellect".

PMID- 9156155
TI  - Tuberculosis in the 1990s--new challenges from the old enemy.

PMID- 9156156
TI  - Lipids and prevention in coronary care.

PMID- 9156157
TI  - Tranquillizers are good for you.

PMID- 9156159
TI  - Medical, military and humanitarian aid.

PMID- 9156158
TI  - The rights and responsibilities of doctors.

PMID- 9156160
TI  - Infection in the organ transplant patient; the Hegelian dialectic of
      transplantation.

PMID- 9156161
TI  - Lettsomian Lecture. Scoliosis and kyphoscoliosis cellular and molecular
      mechanisms inducing spinal curvature.

PMID- 9156162
TI  - Publishing a paper in a medical journal.

PMID- 9156163
TI  - The annual oration. The role of molecular biology in the future of medical
      practice.

PMID- 9156164
TI  - Sir John McNee Bequest. The prevalence of risk factors for coronary artery
      disease in ethnic minorities in patients undergoing cardiac catheterization.
      Report on a period of elective study.

PMID- 9156165
TI  - Sir John McNee Bequest. Christmas at Groote-Schuur Hospital. The outcome and
      management of 35 gunshot wounds to limbs. Report on a period of elective study.

PMID- 9156166
TI  - The Sir John McNee Bequest. Cataract surgery in American and British patients.
      Abridged report on a period of elective study.

PMID- 9156167
TI  - Neuronal correlates of pop-out in cat striate cortex.
AB  - Neuronal responses to static and moving texture patterns were investigated in the
      striate cortex of anaesthetized and paralysed adults cats. Texture patterns were
      composed of a central light bar presented in the excitatory receptive field of a
      cell and an array of many similar elements in the surround. For the static
      condition, elements in the surround were either parallel or orthogonal to the
      centre line (orientation test). For the moving condition, centre and surround
      elements (all at same orientation) moved either in the same or in the opposite
      directions (motion test). Thirty-six percent (31/86) of the neurons tested for
      motion and 24% (24/99) of the neurons tested for orientation responded more
      strongly to the patterns displaying feature contrast than to the uniform
      patterns. These neurons may form a neural basis for visual pop-out of orientation
      and motion.

PMID- 9156168
TI  - A dissociation between brain activity and perception: chromatically opponent
      cortical neurons signal chromatic flicker that is not perceived.
AB  - When two isoluminant colors alternate at frequencies > 10 Hz, we perceive only
      one fused color with a minimal sensation of brightness flicker. In spite of the
      perception of color fusion, color opponent (CO) cells at early stages of the
      visual pathway are known to respond to chromatic flicker at frequencies far
      exceeding the perceptual fusion frequency. To explain color fusion, several
      groups have predicted that CO cells in V1-unlike the retina and lateral
      geniculate nucleus-should not follow high-frequency flicker. To test this
      prediction we recorded from 12 CO cells in various V1 layers. We found, contrary
      to expectations, that these neurons follow high frequency flicker well above
      heterochromatic fusion frequencies. All followed 15 Hz flicker and 10/12 followed
      30 Hz flicker. For three cells, we tested 60 Hz luminance flicker and found clear
      responses. We thus present evidence of cortical activity in alert, trained
      monkeys that is clearly representing visual stimulation, yet is not perceived.
      Our data call into question explanations of perceptual phenomena that invoke a
      low temporal frequency cut-off of CO cells in V1 to account for the failure to
      perceive fast temporal changes in the chromatic domain.

PMID- 9156169
TI  - Preference of peanut agglutinin labeling for long-wavelength-sensitive cone
      photoreceptors in the dace retina.
AB  - Peanut agglutinin (PNA) was known for its selective binding to cone cells. In the
      present study, we investigated whether there was any difference in PNA binding
      among various subtypes of cone photoreceptor cells in the dace retina. The outer
      segments of the long-double- and long-single-cone cells were preferentially
      labeled with PNA. Ultrastructural pre-embedding labeling revealed that the
      binding sites of PNA were confined to the calycal processes of these cells. By
      contrast, only slight labeling was discerned on the corresponding regions of
      other types of cone cells. The results indicate that PNA can distinguish the long
      wavelength-sensitive cone from the short-to-middle-wavelength-sensitive cone
      cells.

PMID- 9156170
TI  - Temporal aspects of contrast visual evoked potentials in the pigmented rat:
      effect of dark rearing.
AB  - Cortical visual evoked potentials (VEPs) in response to gratings temporally
      modulated in counterphase were recorded in normal and dark-reared pigmented rats.
      Temporal modulation was either sinusoidal (0.25-15 Hz, steady state condition) or
      abrupt (0.5 Hz, transient condition). In normals, the amplitude spectrum of
      contrast VEPs has two peaks (at about 0.5 and 4 Hz) and a high temporal frequency
      cut-off of the order of 11 Hz. The VEP phase lags with temporal frequency,
      showing two different linear slopes for separate frequency ranges (0.25-1 Hz and
      1-7 Hz) centred on the peaks of the curve. The different slopes correspond to
      apparent latencies of 500 and 136 msec, respectively. Dark rearing reduced the
      cut-off frequency by about 3 Hz and increased apparent latencies by about 42 msec
      in the low temporal frequency range and 30 msec in the high temporal frequency
      range. The latency of the first peak of transient VEPs was increased by about 47
      msec. Results indicate that the frequency response of rat contrast VEPs is
      qualitatively similar to that of other mammals (including human), albeit shifted
      to a lower range of temporal frequencies. Dark rearing significantly alters the
      VEP temporal characteristics, suggesting that visual experience is necessary for
      their correct development.

PMID- 9156171
TI  - Spatial layout affects speed discrimination.
AB  - We address a surprising result in a previous study of speed discrimination with
      multiple moving gratings: discrimination thresholds decreased when the number of
      stimuli was increased, but remained unchanged when the area of a single stimulus
      was increased [Verghese & Stone (1995). Vision Research, 35, 2811-2823]. In this
      study, we manipulated the spatial- and phase relationship between multiple
      grating patches to determine their effect on speed discrimination thresholds. In
      a fusion experiment, we merged multiple stimulus patches, in stages, into a
      single patch. Thresholds increased as the patches were brought closer and their
      phase relationship was adjusted to be consistent with a single patch. Thresholds
      increased further still as these patches were fused into a single patch. In a
      fission experiment, we divided a single large patch into multiple patches by
      superimposing a cross with luminance equal to that of the background. Thresholds
      decreased as the large patch was divided into quadrants and decreased further as
      the quadrants were maximally separated. However, when the cross luminance was
      darker than the background, it was perceived as an occluder and thresholds, on
      average, were unchanged from that for the single large patch. A control
      experiment shows that the observed trend in discrimination thresholds is not due
      to the differences in perceived speed of the stimuli. These results suggest that
      the parsing of the visual image into entities affects the combination of speed
      information across space, and that each discrete entity effectively provides a
      single independent estimate of speed.

PMID- 9156172
TI  - The bimodality of unique green revisited.
AB  - Unique green measurements were obtained from 50 females and 50 males under eight
      different experimental conditions. Combinations of two different test sizes (0.25
      and 1.0 deg) and four different background fields (none, 62.5, 250, and 1000 td)
      comprised the experimental conditions under which unique green measurements were
      made. Group and gender frequency distributions of the unique green loci were
      examined for the eight experimental conditions. Differences in the shape of the
      frequency distributions were noted for the different test sizes and backgrounds
      as well as for gender, but none of the experimental parameters appeared to elicit
      a statistically significant bimodal distribution.

PMID- 9156173
TI  - Changes in human infants' sensitivity to slow displacements over the first 6
      months.
AB  - Sensitivity to slow movement improves substantially during the early postnatal
      months. Thresholds were measured for slow oscillatory displacements for 68
      infants aged 6, 12, 18, and 24 weeks. Standing wave line stimuli were used; 6
      week-olds were tested at 1.2 Hz, and infants in the three older age groups were
      tested at either 0.6 or 1.2 Hz. Six-week-olds as a group were very insensitive to
      these slow displacements. Sensitivity increased systematically across the three
      older ages. Thresholds were marginally lower at 1.2 Hz than at 0.6 Hz, and there
      was some indication that these thresholds may reflect a mixture of detection by
      position-sensitive and motion-sensitive mechanisms. Several factors are
      hypothesized to be responsible for this development: (1) improvements in spatial
      resolution; (2) improvements in temporal contrast sensitivity; (3) decreases in
      the size of second order motion integration mechanisms; and (4) increased neural
      connectivity in the motion pathways.

PMID- 9156174
TI  - Metric analysis of threshold spectral sensitivity in the honeybee.
AB  - Behavioral spectral sensitivity curves are frequently used to characterize
      peripheral stages of visual processing. We test specific hypotheses about the
      physiology underlying honeybee spectral sensitivity by approximating published
      sensitivity curves with several metric models. The analysis shows that: (1)
      models assuming no interactions between different receptor types do not explain
      the behavioral data. Similarly, neither simple luminance mechanism models (sum of
      receptor excitations), nor models in which only the most sensitive receptor
      determines sensitivity fit the data. (2) The minimum number of postreceptoral
      mechanisms mediating discrimination is two. (3) Both mechanisms are of the
      chromatic type. Adding an achromatic mechanism decreases the accuracy of
      approximation.

PMID- 9156175
TI  - Head-position-dependent adaptation of nonconcomitant vertical skew.
AB  - Vertical phoria can be trained to vary with either head position or orbital eye
      position. The present experiments show that subjects can simultaneously adapt
      their eye-position-specific (nonconcomitant) vertical phorias in different
      directions at different head positions. Eye-position-dependent and head-position
      dependent adaptive pathways, therefore, are not independent. Rather, the
      adaptation of vertical skew takes into account both eye and head position. In
      additional experiments, the magnitude of the nonconcomitant adaptive response was
      shown to be related to otolith output, increasing with head tilt ipsilateral to
      the tilt position at which training was received and decreasing in the
      contralateral direction.

PMID- 9156176
TI  - The perception of motion and structure in structure-from-motion: comparisons of
      affine and Euclidean formulations.
AB  - I investigated the discrimination of rigid from nonrigid structure and the
      perception of affine stretches along the line of sight [Norman & Todd (1993).
      Perception and Psychophysics, 53, pp. 279-291]. Investigations of performance at
      discriminating rigid from nonrigid structure showed that performance improved
      when number of views and amount of simulated three-dimensional nonrigidity
      increased. Investigations of rotations about the vertical which include affine
      stretches along the line of sight compared Euclidean interpretations of affine
      stretching stimuli to human perception. These Euclidean interpretations were
      obtained from a simple algorithm which recovered structure and motion from this
      limited class of stimuli under the assumption that distances to the axis of
      rotation did not change. The algorithm predicted that stretches along the line of
      sight would be perceived as nearly rigid and have variable angular velocity.
      These predictions were supported by subjects' reports of occurrences of
      nonrigidity and minima of angular velocity. The Euclidean algorithm also provided
      measures of nonrigidity and motion coherence, and experimental results were
      consistent with a prediction of when perception of nonrigidity would be
      independent of perception of coherence. The results are discussed relative to the
      advantages and shortcomings of both the affine and Euclidean approaches to
      structure-from-motion.

PMID- 9156177
TI  - The role of 3-D surface slope in a lightness/brightness effect.
AB  - Adelson has shown how two patches in a 5 by 5 array of grey patches can be
      perceived to consist of different shades, depending on whether they are
      represented at a 3-D horizontal or vertical ridge. Adelson interprets the
      illusion in terms of the orientation of the patches with respect to the inferred
      illuminant. We investigated: (1) the illusion in the vertical and horizontal
      stimuli and added a flat (ridgeless) control stimulus; (2) stimuli of varying
      ridge amplitudes to examine the effect more fully. 3-D renderings of real
      surfaces were modelled with computer graphics and displayed to observers who used
      a mouse to alter the brightness of a square to match patches indicated in the
      stimuli. Five observers were used for the vertical, flat and horizontal stimuli,
      while a larger group (n = 20) was used for an independent design when varying
      ridge amplitudes. A significant effect in the flat surface demonstrates that
      patches lying in the same plane can have their brightness altered without changes
      in their orientation. When the surface was seen as a 3-D ridge the size of the
      effect was a function of 3-D slope of the surface. By measuring each patch
      independently we have shown that the effect changes the brightness of the two
      patches to differing degrees. We offer an explanation of this based on a proposed
      qualitative shading rule for identifying reflectance and illumination edges.

PMID- 9156178
TI  - Psychophysical evidence for losses in rod sensitivity in the aging visual system.
AB  - Rod sensitivity was measured with a criterion-free psychophysical method at 10
      deg in the horizontal meridian of the nasal field of the left eye on 26 young
      (mean age, 24.1 yr) and 14 older (mean age 72.6 yr) observers in good ocular
      health. A 1 deg, 90 msec stimulus was delivered by means of a free-viewing
      optical system under computer control. Stimulus wavelengths were chosen to have
      either significant (406 nm) or minimal (560 nm) absorption by the older lens.
      After correction for senile miosis and lens density, 0.39 log unit higher
      thresholds for the older observers remained and are interpreted as being due to
      neural factors.

PMID- 9156179
TI  - Stereopsis and disparity vergence in monkeys with subnormal binocular vision.
AB  - The surgical treatment for strabismus in infants generally results in microtropia
      or subnormal binocular vision. Although the clinical characteristics of these
      conditions are well established, there are important questions about the
      mechanisms of binocular vision in these patients that can best be investigated in
      an appropriate animal model. In the present psychophysical investigations,
      spatial frequency response functions for disparity-induced fusional vergence and
      for local stereopsis were studied in macaque monkeys, who demonstrated many of
      the major visual characteristics of patients whose eyes were surgically aligned
      during infancy. In six rhesus monkeys, unilateral esotropia was surgically
      induced at various ages (30-184 days of age). However, over the next 12 months,
      all of the monkeys recovered normal eye alignment. Behavioral measurements at 4-6
      years of age showed that the monkeys' prism-induced fusional vergence responses
      were indistinguishable from those of control monkeys or humans with normal
      binocular vision. Investigations of stereo-depth discrimination demonstrated that
      each of the experimental monkeys also had stereoscopic vision, but their
      stereoacuities varied from being essentially normal to severely stereo-deficient.
      The degree of stereo-deficiency was not related to the age at which surgical
      esotropia was induced, or to the presence or absence of amblyopia, and was not
      dependent on the spatial frequency of the test stimulus. Altogether, these
      experiments demonstrate that a temporary, early esotropia can affect the
      binocular disparity responses of motor and sensory components of binocular vision
      differently, probably because of different sensitive periods of development for
      the two components.

PMID- 9156180
TI  - Characterization of glutamate transporter function in the tiger salamander
      retina.
AB  - Glutamate transporters in the tiger salamander retina were studied by
      autoradiographic and intracellular recording techniques. When the retina was
      incubated with 15 microM L-[3H]glutamate, photoreceptors and Muller cells were
      labeled, indicating that these cells had high-affinity glutamate uptake
      transporters. A much higher dose of glutamate than kainate was required in the
      bath to produce the same membrane depolarization in horizontal cells (HCs), and
      the time course of glutamate-induced depolarization was much slower than that of
      the kainate-induced depolarization. Since glutamate is a substrate of glutamate
      transporters whereas kainate is not, we attribute these differences to the
      buffering of extracellular glutamate by glutamate transporters in the retina. D
      aspartate (D-asp) increased the efficacy of bath-applied glutamate.
      Dihydrokainate (DHKA) exerted little effect on glutamate efficacy when applied
      alone, but it increased glutamate efficacy in the presence of D-asp. These
      results are consistent with the notion that glutamate transporters in Muller
      cells are D-asp sensitive and those in photoreceptors are DHKA and D-asp
      sensitive. Application of DHKA (1-2 mM) did not affect the dark membrane
      potential or the light responses in rods and cones, but it depolarized the HC
      dark membrane potential and reduced the HC peak and tail light responses. Our
      results suggest that DHKA-sensitive glutamate transporters in photoreceptors
      regulate glutamate levels in rod and cone synaptic clefts. They modulate dark
      membrane potential and the relative rod cone inputs in retinal HCs.

PMID- 9156181
TI  - Responses of complex cells in cat area 17 to apparent motion of random pixel
      arrays.
AB  - The characteristics of directionally selective cells in area 17 of the cat are
      studied using moving random pixel arrays (RPAs) with 50% white and 50% black
      pixels. The apparent motion stimulus is similar to that used in human
      psychophysics [Fredericksen et al. (1993). Vision Research, 33, pp. 1193-1205].
      We compare motion sensitivity measured with single-step pixel lifetimes and
      unlimited pixel lifetimes. A motion stimulus with a single-step pixel lifetime
      contains directional motion energy primarily at one combination of spatial
      displacement and temporal delay. We recorded the responses of complex cells to
      different combinations of displacement and delay to describe their spatio
      temporal correlation characteristics. The response to motion of RPAs with
      unlimited lifetime is strongest along the preferred speed line in a delay vs
      displacement size diagram. When using an RPA with a single-step pixel lifetime,
      the cells are responsive to a much smaller range of spatial displacements and
      temporal delays of the stimulus. The maximum displacement that still gives a
      directionally selective response is larger when the preferred speed of the cell
      is higher. It is on average about three times smaller than the receptive field
      size.

PMID- 9156183
TI  - Direction-selective coding of stereoscopic (cyclopean) motion.
AB  - This study employed a selective adaptation paradigm and investigated thresholds
      for direction discrimination of translational stereoscopic motion (moving
      binocular disparity information). The stimuli were moving arrays of randomly
      positioned stereoscopic discs created from disparity embedded in dynamic random
      element stereograms. When discrimination thresholds were measured across a range
      of base directions following adaptation in a fixed direction, discrimination
      thresholds were maximally elevated 20-30 deg away from adaptation and reduced in
      the same direction as adaptation. These results are consistent with a distributed
      channel model of direction coding and indicate that the direction of stereoscopic
      motion is encoded by adaptable direction-selective mechanisms similar to those
      proposed for luminance-defined motion.

PMID- 9156182
TI  - Visual responses of neurons from areas V1 and MT in a monkey with late onset
      strabismus: a case study.
AB  - One adult monkey (Macaca fascicularis) was investigated psychophysically and
      electrophysiologically after at least 5 years of late onset esotropic
      macrostrabismus (squint angle 52 deg). Behavioural tests revealed normal
      monocular visual and visuomotor functions. No indications of deep amblyopia or
      oculomotor asymmetry were found. The monkey used the left or right eye
      alternately at about equal frequencies. Single unit recordings from area VI
      disclosed a normal ocular dominance distribution. Most VI neurons from both
      hemispheres received binocular input. Thus, discordant visual information from
      corresponding retinal locations of the two eyes converged onto the cortical
      neurons. No evidence for anomalous retinal correspondence was found. Diplopia and
      confusion must therefore be avoided by suppression of vision through one eye to
      allow stable, unambiguous perception. Possible suppression was investigated by
      stimulating a neuron through the same eye when it was actively used for fixation
      in one set of trials, and when it was not used for fixation in another set of
      trials. Significant differences in these two stimulus conditions were found in
      20/39 neurons from area VI and in 11/34 motion sensitive neurons recorded in the
      middle superior temporal area (MT). The normalized population activity in VI and
      MT was higher if cells were stimulated through the fixating eye. The data are
      discussed with respect to possible suppressive mechanisms helping to prevent
      double vision in strabismus and in binocular rivalry.

PMID- 9156184
TI  - Speed discrimination of stereoscopic (cyclopean) motion.
AB  - This study investigated the degree to which speed of stereoscopic translational
      motion (i.e. moving binocular disparity information) can be discriminated in a
      display that minimizes position information. Observers viewed dynamic random
      element stereograms depicting arrays of randomly positioned stereoscopic dots
      that moved bidirectionally. Two tasks were performed: a speed discrimination task
      and a displacement discrimination task. Across a range of conditions, speed could
      be discriminated under conditions in which displacement could not. Thus, speed of
      stereoscopic motion can be discriminated when position information is minimal.
      This result indicates that stereoscopic motion is sensed in a way that cannot be
      explained by feature tracking or by inferring the motion from memory of position
      and time.

PMID- 9156185
TI  - Across-object relationships in perceived object orientation.
AB  - An orientation discrimination paradigm was used to determine whether the
      perceived orientation of extended objects is based on the distribution of edge
      orientations or on the response of mechanisms that encode relationships across
      the object; specifically we considered large, second-stage filters and cores (the
      perceived middle of the object) as encoders of the across-object relationship.
      The stimuli were "rectangles" with sinusoidally modulated long edges.
      Manipulating the frequency and relative phase of the edge modulation allowed us
      to assess the importance of the across-object relationships. Evidence was found
      for the importance of such relationships in determining perceived orientation. No
      evidence was found for direct use of the distribution of responding edge
      detectors.

PMID- 9156186
TI  - Hue scaling of isoluminant and cone-specific lights.
AB  - Using a hue scaling technique, we have examined the appearance of colored spots
      produced by shifts from white to isoluminant stimuli along various color vectors
      in order to examine color appearance without the complications of the combined
      luminance and chromatic stimulation involved in most previous hue scaling
      studies, which have used flashes of monochromatic light. We also used spots lying
      along cone-isolating vectors in order to determine what hues would be reported
      with a change in activation of only single cone types or of only single
      geniculate opponent-cell types, an issue of direct relevance to any model of
      color vision. We find that: 1. Unique hues do not correspond either to the change
      in activation of single cone types or of single geniculate opponent-cell types.
      This is well known to be the case for yellow and blue, but we find it to be true
      for red and green as well. 2. These conclusions are not limited to the particular
      white (Illuminant C) used as an adapting background in most of the experiments.
      Shifts along the same cone-contrast vectors relative to different backgrounds
      lead to much the same hue percepts, independent of the starting white used. 3.
      The shifts of the perceptual colors from the geniculate axes are in the
      directions, and close to the absolute amounts, predicted by our [De Valois & De
      Valois (1993). Vision Research, 33, 1053-1065] multi-stage color model in which
      we postulate that the S-opponent cells are added to or subtracted from the M- and
      L-opponent cells to form the four perceptual color systems. 4. There are distinct
      asymmetries with respect to the extent to which various hues within each
      perceptual opponent system deviate from the geniculate opponent-cell axes. Blue
      is shifted more from the S-LM axis than is yellow; green is shifted more from the
      L-M axis than is red. There are also asymmetries in the angular extent of
      opponent color regions. Blue is seen over a larger range of color vectors than is
      yellow, and red over a slightly larger range than green. 5. Such asymmetries are
      not accounted for by any model that treats red-green and yellow-blue each as
      unitary, mirror-image opponent-color systems. Although red and green are
      perceptually opponent, the red and green perceptual systems do not appear to be
      constructed in a mirror-image fashion with respect to input from different cone
      types or from different geniculate opponent-cell types. The same is true for
      yellow and blue.

PMID- 9156187
TI  - Infant color vision: moving tritan stimuli do not elicit directionally
      appropriate eye movements in 2- and 4-month-olds.
AB  - The purpose of the present study was to investigate the capacity of infants to
      code the direction of motion of moving tritan-modulated gratings. Infant and
      adult subjects were tested with 0.2 c/d sinusoidal gratings moving at a speed of
      20 deg/sec. Three conditions were tested: luminance-modulated gratings, tritan
      modulated gratings, and luminance- vs tritan-modulated gratings superimposed and
      moving in opposite directions in a chromatic motion nulling paradigm. Two-month
      old infants were tested in all three conditions, while 4-month-olds were tested
      in only the first two conditions. For infant subjects, an adult observer reported
      the direction of the slow phase of the infant's eye movements; adult subjects
      judged the perceived direction of motion of the stimuli. Luminance-modulated
      gratings produced directionally appropriate eye movements (DEM) in all age
      groups. Tritan gratings presented alone did not produce DEM in either 2- or 4
      month-olds, but did so in adults. Mean equivalent luminance contrasts were near
      zero in 2-month-olds, and small but reliably above zero in adults. In sum, the
      present study provides no evidence that infants can code the direction of motion
      of moving tritan gratings.

PMID- 9156188
TI  - Contour integration across polarities and spatial gaps: from local contrast
      filtering to global grouping.
AB  - This article introduces an experimental paradigm to selectively probe the
      multiple levels of visual processing that influence the formation of object
      contours, perceptual boundaries, and illusory contours. The experiments test the
      assumption that, to integrate contour information across space and contrast sign,
      a spatially short-range filtering process that is sensitive to contrast polarity
      inputs to a spatially long-range grouping process that pools signals from
      opposite contrast polarities. The stimuli consisted of thin subthreshold lines,
      flashed upon gaps between collinear inducers which potentially enable the
      formation of illusory contours. The subthreshold lines were composed of one or
      more segments with opposite contrast polarities. The polarity nearest to the
      inducers was varied to differentially excite the short-range filtering process.
      The experimental results are consistent with neurophysiological evidence for
      cortical mechanisms of contour processing and with the Boundary Contour System
      model, which identifies the short-range filtering process with cortical simple
      cells, and the long-range grouping process with cortical bipole cells.

PMID- 9156189
TI  - Open loop optokinetic responses of the turtle.
AB  - Turtle eye movements were measured during full-field horizontal optokinetic
      stimulation under closed and open loop conditions. Because these animals display
      unyoked slow-phase eye movement behavior, open loop stimulation could not be
      presented to a paralyzed eye, while monitoring the position of the contralateral
      eye. The turtle's optokinetic reflex loop was opened electronically by a
      continuous adjustment of the pattern's position that effectively canceled the
      effect of the movement of the recorded eye. The highest open loop gains (2-3)
      were observed at low speeds (< 1 deg/sec), demonstrating a more limited speed
      range and lower gain in turtle than in the mammalian optokinetic system. These
      results in the intact animal can be correlated with the visual response
      properties of the turtle's pretectum and accessory optic system recorded in
      vitro.

PMID- 9156190
TI  - Relative orientation of primary positions of the two eyes.
AB  - We evaluated the relative orientations of the displacement planes of the two eyes
      under various conditions: fixations of nearby targets, of far targets and targets
      presented dichoptically at optical infinity. We show that disparity driven
      vergence is not always required to rotate the primary positions. We find that eye
      orientation during fixation of far targets is idiosyncratic. We found a bimodal
      distribution ranging from null to about 30 deg of the relative exorotations of
      the two primary positions. By contrast, the difference of primary positions'
      orientation of the two eyes was, for targets at optical infinity, stable and
      similar across subjects. However, the displacement planes of the two eyes did not
      coincide, but were exorotated by 4.3 deg on average, even though horizontal
      vergence was close to zero. We discuss our results with reference to current
      models of binocular three-dimensional control.

PMID- 9156191
TI  - Very short-term visual memory via reverberation: a role for the cortico-thalamic
      excitatory circuit in temporal filling-in during blinks and saccades?
AB  - There is a large projection of neurons from Layer VI of V1 that makes excitatory
      connections on LGN relay cells. It has been proposed that this circuit is
      involved in signal processing and thalamic sensitivity regulation. Alternatively,
      Crick has suggested that the circuit could be a reverberatory loop-a site for
      very short-term (iconic) visual memory. This hypothesis is shown to be plausible
      if the reverberation is keyed to the onset of neurally initiated visual
      disruptions such as blinks and saccades. Neural mechanisms suppress perception
      during these events but little is known about temporal filling-in processes
      analogous to the mechanisms that fill-in spatial scotomas. Crick's reverberatory
      loop could provide a process for filling-in temporal scotomas with information
      acquired just before the disruption, thus maintaining the continuity of visual
      experience.

PMID- 9156192
TI  - Motion coherence perimetry in glaucoma and suspected glaucoma.
AB  - Motion direction sensitivity in glaucoma patients, glaucoma suspects and controls
      was assessed perimetrically at 22 visual field locations using small random dot
      kinematograms and a motion coherence task. For foveal stimulus presentations,
      mean motion coherence sensitivity was normal in both patient groups. However,
      nearly all glaucoma patients and about half of glaucoma suspects (all with normal
      visual fields as assessed with static perimetry) had some deficit of motion
      sensitivity. These were most pronounced and most prevalent in the superior field
      at 15 and 21 deg eccentricity. Glaucoma appears to produce a reduction in the
      normal integrative visual function necessary for the perception of global motion
      in textured displays and this disruption is non-uniformly distributed across the
      visual field.

PMID- 9156193
TI  - Some remarks on the magnocellular deficit theory of dyslexia.

PMID- 9156194
TI  - Primary structure of locust opsins: a speculative model which may account for
      ultraviolet wavelength light detection.
AB  - The sequences of two locust opsins have been determined by dideoxy nucleotide
      sequencing of PCR products from cDNA derived from eyecup tissue. The opsins (Lo1
      and Lo2) are encoded by 381 and 380 amino acid residues, respectively, with
      hydropathy profiles and placement of key amino acid residues suggestive of a
      typical seven-transmembrane rhodopsin structure. The sequence alignment of Lo1
      reveals significant homology to mantid opsin. These opsins contain retinal as
      their visual chromophore and have similarity to the Rh1 type sequences from
      Drosophila and Calliphora which use 3-hydroxy retinal. Lo2 is most closely
      related to the Rh3/4 type of visual pigments from Drosophila. The retinal-based
      opsins show reduced numbers of charged amino acids in the loop region connecting
      transmembrane segments V and VI compared to the 3-hydroxy retinal opsins.
      Sequence alignment of all the known insect visual pigments has shown that only
      those with maximal sensitivity in the blue/UV spectral range, Lo2 and the Rh3/4
      opsins of Drosophila, have three charged amino acids in transmembrane segments
      II, IV and VII. The charged residue in transmembrane VII is two helical turns
      away from the positively charged Schiff base and could act directly as a
      counterion to it. From the secondary structure analysis of opsin, the two charged
      residues in transmembrane II and IV would be in close proximity to form a dipole.
      These polar motifs in Lo2 and Rh3/Rh4 could act in wavelength modulation of short
      wavelength sensitive pigments and substantiate the proposed external two-point
      charge model which accounts for the spectral sensitivity of visual pigments
      [Honig, B., Dinur, U., Nakanishi, K., Balogh-Nair, V., Gawinowicz, M.A. and
      Motto, M. (1979). Journal of the American Chemical Society, 101, 7084-7086].

PMID- 9156195
TI  - Effects of ageing on spatial aspects of the pattern electroretinogram in male and
      female quail.
AB  - This study deals with age-related functional changes in the eye of quail.
      Measurements of lens refractive state and transmission, as well as pupil
      diameter, showed that the quail's eye became more myopic with increasing age, but
      no change could be detected in lens transmission and pupil diameter. Three
      aspects of the pattern electroretinogram (PERG) were studied after correcting for
      ocular refraction: (i) spatial characteristics (visual acuity and contrast
      sensitivity); (ii) maximal amplitude; and (iii) peak latency. The PERG results
      suggested that the visual acuity was age-independent for both sexes. However, the
      contrast sensitivity of the old quail (16-20 months) was much lower (1.5-3 times)
      than that of the young (3-6 months) at low to intermediate (< 2 c/d), but not at
      high spatial frequencies. The peak latency of the PERG response was 3-4 msec
      longer in the old birds compared with the young, while the maximal amplitude of
      the PERG response was age-independent. These results clearly suggested that at
      least some of the age-induced changes are located in the neural retina.

PMID- 9156196
TI  - Disentangling the role of spatial scale, separation and eccentricity in Weber's
      law for position.
AB  - Factors underlying Weber's law for position were investigated by measuring
      spatial interval discrimination accuracy for spectrally narrow-band stimuli.
      These stimuli were positioned around an iso-eccentric arc in order to allow
      separation and eccentricity to be varied independently. We find that Weber's law
      occurs at individual spatial scales, and holds true not just for stimuli
      positioned either side of fixation, but for any series of stimuli which possess
      the same ratio of separation to eccentricity. When the separation/eccentricity
      ratio is large, thresholds are proportional to eccentricity and demonstrate
      contrast independence. At smaller separation/ eccentricity ratios, thresholds are
      determined by a contrast-dependent combination of separation and eccentricity.

PMID- 9156197
TI  - Resolution acuity is better than vernier acuity.
AB  - Our impressive sensitivity to vernier offsets as compared to resolution acuity
      has long inspired vision researchers to study the phenomena in great detail. In
      this study we use the test-pedestal framework to compare resolution and vernier
      acuity. In these experiments the test stimulus is the same for both tasks, only
      the pedestals differ. When thresholds are expressed in common units of test
      strength, vernier acuity thresholds are higher (worse) than for resolution and
      contrast discrimination tasks over the range of pedestal strengths tested. This
      apparent reversal of sensitivity is actually consistent with expectations based
      on the presumed underlying visual mechanisms involved in the tasks.

PMID- 9156198
TI  - Probing visual motion signals with a priming paradigm.
AB  - The perceived motion of a vertical sine-wave luminance grating which undergoes an
      abrupt 180 deg phase shift (motion step) is ambiguous. The grating sometimes
      appears to move rightward; sometimes leftward. However, when the 180 deg step
      follows closely upon an unambiguous grating step, the 180 deg step appears to be
      in the same direction as the unambiguous step. This phenomenon is termed visual
      motion priming (VMP), and some of the characteristics of the phenomenon were
      investigated in a series of experiments. The main findings were that priming (1)
      lasted for hundreds of msec; (2) was at a maximum when the magnitude of the
      priming step was 90 deg; (3) was scarcely affected by spatial frequency in the
      range 0.7-2.8 c/deg; and (4) at suprathreshold contrasts depended upon the
      relative contrast, not the absolute contrasts, of the frames comprising the
      priming step. The experiments were conducted within the framework of a motion
      energy model (Adelson & Bergen, 1985) which possessed an extra stage which summed
      motion signals over time. Some of the results could be explained by the second
      stage integrator. Other nonlinear relationships between VMP and contrast require
      some form of motion signal compression, and perhaps even a mechanism of dynamic
      contrast processing.

PMID- 9156199
TI  - Contrast dependencies of two types of motion aftereffect.
AB  - We examined the effects of adaptation and test contrasts on the duration of two
      types of motion aftereffect (MAE) that presumably reveal different levels of
      motion processing: MAE with a static test stimulus (static MAE), and that with a
      counterphasing test stimulus (flicker MAE). MAE duration increased with
      increasing adaptation contrast. When the test contrast was low, it increased
      rapidly, and saturated at a low adaptation contrast. When the test contrast was
      high, however, it gradually increased over a wide range of adaptation contrasts.
      These complex effects of stimulus contrasts could be well described by a
      dependency on adaptation contrast normalized by test contrast on a logarithmic
      axis. Little difference was found between the results for two types of MAE. The
      interaction between adaptation and test contrasts leads us to reject the idea
      that the shape of adaptation contrast dependency of MAE duration reflects that of
      the sensitivity function of motion detecting mechanisms. The results also suggest
      a functional similarity between the processes underlying static and flicker MAEs
      with regard to their responses to contrasts.

PMID- 9156200
TI  - Human discrimination of the implicit orientation of simple symmetrical patterns.
AB  - Thresholds for detecting the angle of rotation of vertical symmetrical patterns
      containing few or no explicit vertical or horizontal contours were found to be
      almost as low as those for an actual vertical line extending approximately the
      same range. This hyperacuity performance, which we refer to as implicit
      orientation discrimination, shares most of its properties with the orientation
      discrimination of explicit lines, suggesting a category of orientation processing
      whose neural mechanisms are related to those involved in the processing of
      straight contours and those underlying the detection of axes of symmetry. Strong
      binding effects between the components of the figures were demonstrated and their
      temporal interactions were also investigated. Our results have implications for
      possible neural interactions early in the cortical visual stream.

PMID- 9156201
TI  - Human heading estimation during visually simulated curvilinear motion.
AB  - Recent studies have suggested that humans cannot estimate their direction of
      forward translation (heading) from the resulting retinal motion (flow field)
      alone when rotation rates are higher than approximately 1 deg/sec. It has been
      argued that either oculomotor or static depth cues are necessary to disambiguate
      the rotational and translational components of the flow field and, thus, to
      support accurate heading estimation. We have re-examined this issue using
      visually simulated motion along a curved path towards a layout of random points
      as the stimulus. Our data show that, in this curvilinear motion paradigm, five of
      six observers could estimate their heading relatively accurately and precisely
      (error and uncertainty < approximately 4 deg), even for rotation rates as high as
      16 deg/sec, without the benefit of either oculomotor or static depth cues
      signaling rotation rate. Such performance is inconsistent with models of human
      self-motion estimation that require rotation information from sources other than
      the flow field to cancel the rotational flow.

PMID- 9156202
TI  - Influence of the luminance and opponent chromatic channels on stereopsis with
      random-dot stereograms.
AB  - The present work examines the relationship between random-dot stereograms (via
      the disparity range parameter) and color-vision mechanisms (via the luminance
      channel and red-green and tritan directions at isoluminance). The results clearly
      indicate that the variations in the stereograms along red-green confusion lines
      contribute to stereopsis. Stereoscopic perception depends on spatial information
      for stereograms generated with variations along tritan confusion lines. For
      observers who perceive stereopsis via tritan directions, the results show a
      gradation in the disparity range, with the disparity range for stereograms
      generated by luminance variations being greater than for stereograms generated in
      red-green directions; the latter range is, in turn, greater than for stereograms
      generated along tritan directions.

PMID- 9156203
TI  - Spatial interactions with real and gap-induced illusory lines in vernier acuity.
AB  - Vernier acuity for illusory line targets induced by gaps in a horizontal grating
      was measured in the presence of real and illusory flanks. In a 500 msec
      presentation forced choice task, observers judged the position of a comparison
      illusory line positioned 3 min arc below the target. The results show that
      illusory lines are capable of interacting with real lines in spatial
      localization. Thus, they provide psychophysical evidence for a common
      localization mechanism that supports real and illusory contour definitions. The
      results further show a sensitivity of the visual system to the contrast polarity
      of real lines. This sensitivity was absent for illusory lines. The present
      findings are discussed in terms of their relationship to physiological findings,
      and in terms of their potential to constrain computational models that account
      for illusory contour brightness.

PMID- 9156204
TI  - Order-specific and non-specific motion responses in the human visual system.
AB  - A series of experiments measured direction discrimination in two-frame random
      block kinematograms. Blocks were presented against a uniform grey background, and
      were filled either with uniform grey (darker or brighter than the background;
      first-order blocks) or with random microtexture (isoluminant with the background;
      second-order blocks). Experiment 1 found that when blocks maintained their order
      from frame to frame, performance declined from near-perfect to chance levels as
      block displacement increased. When blocks switched order between frames,
      performance was generally worse (65-75% correct at best), but still above chance
      levels. Results from control experiments established that it is important to
      remove intensity cues in second-order patterns using a psychophysical technique,
      and that above-chance responses with order-switching patterns persisted, even
      when such intensity cues were removed or randomised. The last experiment measured
      the effects of block density manipulation. First-order and second-order patterns
      showed the same decline in Dmax performance as pattern density increased, and
      results from patterns containing a mixture of first- and second-order blocks
      could be predicted from performance obtained with each set of blocks presented
      separately, except at very low densities. It is concluded that both order
      specific and non-specific responses are available during motion analysis, but
      order-specific responses tend to predominate.

PMID- 9156205
TI  - Increment-decrement asymmetry in dichoptic matching with haploscopically
      superimposed backgrounds.
AB  - Chichilnisky & Wandell [(1995). Vision Research, 35, 239-254], studying dichoptic
      asymmetric colour matching with haploscopically superimposed backgrounds
      explained their data in terms of a model that assumes incremental multiplicative
      sensitivity control. The model given in Mausfeld & Niederee [(1993). Perception,
      22, 427-462] postulates a different incremental multiplicative sensitivity
      control for incremental and decremental stimuli. It accounts for systematic
      deviations between Chichilnisky and Wandell's predictions and data as well as for
      a certain type of increment-decrement asymmetry not compatible with their model.

PMID- 9156206
TI  - Saccade target selection during visual search.
AB  - Five experiments are reported in which eye movements were recorded while subjects
      carried out a visual search task. The aim was to investigate whether an accurate
      initial target directed saccade could be programmed. In experiments 1-2, subjects
      moved their eyes to targets defined by colour, which were presented with seven
      non-targets in a circular array. Accurate saccades with short latencies were
      common but errors sometimes occurred and search for an "oddity" target, defined
      exclusively by difference in colour from a homogeneous set of distractors, was
      particularly error prone. In Experiment 3, occasional trials contained double
      targets. First saccades sometimes landed at an intermediate position between the
      targets. In Experiments 4 and 5, targets were presented with 15 distractors in
      two concentric rings of 8. Targets specified by shape could be located accurately
      with a single saccade. Search for a colour-shape conjunction was more difficult
      but targets in the inner ring were located frequently with a single saccade. The
      results suggest that the control of the initial eye movement during both simple
      and conjunction searches is through a spatially parallel process.

PMID- 9156207
TI  - Binocular matching of dissimilar features in phantom stereopsis.
AB  - Previously we have demonstrated that quantitative depth perception can be
      elicited from a stereogram that lacks contrast defined binocular corresponding
      elements (phantom stereopsis). In this report, we use computer simulation to
      demonstrate that it is biologically plausible for some known binocular cortical
      cell types to combine non-conventional matching features. Therefore, binocular
      matching processes based on the responses of these cells could be a conventional
      one, namely, looking for similar response patterns in the two eyes. While at cell
      types we simulated gave identical disparity outputs to the conventional
      stereogram, they responded differently to the phantom stereogram. Processes other
      than low-level disparity detectors may have to be invoked in order to achieve a
      unique depth solution.

PMID- 9156208
TI  - Blending transparent motion patterns in peripheral vision.
AB  - Human observers are very good at segmenting visual scenes consisting of multiple
      moving objects. Segregation of transparent motions, however, turns out to be a
      predominantly central vision process. In peripheral vision transparent motions
      are blended to form a single novel pattern whose coherent motion corresponds to
      the average of the separate motions, whilst sensitivity to small differences in
      coherent motion is maintained. These results point to distinct peripheral
      processing mechanisms with the advantage of being able to detect changes in
      motion fields quickly and accurately.

PMID- 9156209
TI  - The effect of stimulus size on human cortical potentials evoked by chromatic
      patterns.
AB  - The effect of stimulus size on the pattern onset-offset visual evoked potential
      elicited with stimuli of two different wavelengths is studied under intensive
      yellow adaptation: (1) The onset response obtained with a 460 nm pattern is of
      negative polarity (N1) and saturates in amplitude with a stimulus radius of 7
      deg. The onset response obtained with a 550 nm pattern is of positive polarity
      and continues to increase up to the maximum size (32.2 deg). (2) The peak time of
      N1 (460 nm) decreases with increasing stimulus size, that of P1 (550 nm) remains
      constant. These results are discussed as reflecting either varying retinal and
      brain anatomy, or cone activity, color-opponent activity, or luminance contrast
      activity.

PMID- 9156210
TI  - Local changes in eye growth induced by imposed local refractive error despite
      active accommodation.
AB  - We have tested whether defocus imposed on local retinal areas can produce local
      changes in eye growth, even if accommodation is available to clear part of the
      imposed defocus. Hemi-field lenses were attached to little leather hoods that
      were worn by young chickens from day 11-15 post-hatching. The lens segments
      defocused either the nasal or the temporal visual field, or covered the full
      field. We found that negative lenses (-7.5 D) were incompletely compensated in
      all three cases but caused significant myopia in the defocused parts of the
      visual field (differences to fellow eyes with normal vision: nasal visual field 
      3.13 +/- 1.56 D, P < 0.001; temporal visual field -4.02 +/- 1.38 D, P < 0.001;
      full field -3.82 +/- 2.48 D, P = 0.01). Myopia was not enhanced if the lenses
      covered the entire visual field. Positive lenses (+6.9 D) caused larger changes
      in refraction than negative lenses and, again, there was no significant
      difference in the amount of induced hyperopia in the nasal or temporal retina, or
      in the amount of hyperopia with full-field lenses (difference to fellow eyes with
      normal vision: nasal visual field +6.2 +/- 2.69 D, P < 0.001; temporal visual
      field +5.95 +/- 2.22 D, full field +7.22 +/- 2.44 D, P < 0.001). To compare the
      shapes of the excised eyes after lens treatment, we wrote a fully automated image
      processing program that traced their outlines in digitized video images. We found
      that the shapes of the eyes treated with positive lenses did scarcely differ from
      their fellow eyes with normal vision, indicating that hyperopia over this 4 day
      period was caused mostly by choroidal thickening. Full field negative lenses
      produced significant axial eye elongation; the effects of locally imposed defocus
      on eye shape were less conspicuous and were significant only in some areas. That
      local compensation of defocus was possible for both negative and positive lenses,
      suggests that the retina can recognize the sign of defocus without accommodation
      cues. Even more striking is that the presence of accommodation is apparently
      ignored since the drift in the plane of focus during accommodation does not
      disturb the compensation process. We re-analyze previous experimental results
      that argue for different mechanisms for deprivation myopia and lens-induced
      refractive errors. We propose that lens-induced refractive errors are compensated
      by similar retinal mechanisms as the ones proposed by Bartmann and Schaeffel
      [(1994). Vision Research, 34, pp. 873-876] to explain deprivation myopia. The
      proposed mechanisms can integrate with long time constants over the spatial
      frequency content in the retinal image while the viewing distances change, and
      control both choroidal thickening and scleral growth. However, it turns out that
      the compensation of imposed myopia cannot be explained if only one constant
      viewing is available. Apparently, there is more than a retinal blur detector to
      guide refractive development.

PMID- 9156211
TI  - An electrophysiological metric of activity within the ON- and OFF-pathways in
      humans.
AB  - Several animal studies have shown an anatomical and functional separation between
      the ON- and OFF-pathways in the retina and in the lateral geniculate nucleus.
      Psychophysical studies in humans have also documented separate pathways that
      process increments and decrements of light. However, at the level of the visual
      cortex, there is electrophysiological evidence of interactions between the ON-
      and OFF-pathways. In addition, psychophysical studies have shown that these
      pathways can exhibit differential sensitivity and be differentially adapted.
      These findings motivated an electrophysiological study to gather further evidence
      of processing within the ON- and OFF-pathways in the human visual system. Using
      sawtooth stimulus modulation, we measured the visual evoked potential (VEP)
      before and after adaptation to both rapid-on and rapid-off sawtooth stimuli. The
      effect of adaptation was determined by comparing the VEP response in three test
      conditions: without adaptation, after adaptation to the same sawtooth polarity,
      and after adaptation to the opposite sawtooth polarity. The results reveal a
      selective adaptation effect, which provides physiological evidence for separate
      processing of increments and decrements in the human visual system. We conclude
      that with appropriate stimulus parameters, the VEP can serve as an objective
      measure of processing within the ON- and OFF-pathways in humans.

PMID- 9156212
TI  - M and P components of the VEP and their visual field distribution.
AB  - To study components related to parallel processing of information across the
      visual field, multi-focal pattern reversal visual evoked potentials (VEPs) were
      recorded using binary m-sequences. Contrast, chromatic, spatial and temporal
      characteristics of the stimuli were varied in order to favor contributions from
      either M or P pathways. Responses were decomposed into two additive components
      whose behavior was consistent with that of M and P mechanisms. The results
      suggest that contributions to the VEP from the M pathway precede those from the P
      pathway, and that the ratio of P/M contributions decreases with eccentricity.

PMID- 9156213
TI  - Integrating contours within and through depth.
AB  - To better understand the role of disparity in contour integration we compared
      detection performance of "paths" composed of elements confined either to a single
      depth plane, or spanning multiple depth planes. In both cases paths defined by
      alignment of elements were embedded in a noise background-field made up of
      similar, but randomly positioned, elements covering the same depth range as the
      path elements. We show that a systematic disparity cue can enhance the
      detectability of paths which traverse depth, but that this detectability is weak
      compared to paths made up of elements of the same disparity. These results
      suggest that the outputs of disparity detectors tuned to different disparities
      can be linked to define contours.

PMID- 9156214
TI  - Analytic approximation of the off-axis modulation transfer function of the eye.
AB  - Published experimental measurements of the ocular modulation transfer function
      (MTF) in the peripheral field are approximated by the expression T(f) = exp[
      (f/fc)n], where T(f), f, fc, and n are modulation transfer, spatial frequency,
      spatial frequency constant and MTF index, respectively. It is shown that n (which
      describes the shape of the MTF) remains relatively constant at about 0.9 for
      field angles out to 40 deg but fc (which defines the spatial frequency scaling)
      declines steeply over this range, depending upon the pupil diameter and
      conditions of focus. The oblique astigmatism of the eye plays a major role in the
      off-axis changes in fc at field angles > or = 20 deg. The approximation may be
      useful in allowing the form of the degraded optical stimulus in studies of the
      peripheral retinal function to be evaluated.

PMID- 9156215
TI  - Perception of moving lines: interactions between local perpendicular signals and
      2D motion signals.
AB  - An oblique line translating vertically behind a horizontal rectangular aperture
      is perceived as moving in the horizontal direction, i.e., in the line-ending's
      direction. When a feature is added on the line, and thus provides a vertical
      unambiguous motion signal, the line's perceived direction is still horizontal. In
      parallel, the feature appears to slide obliquely along the line (Wallach, 1935).
      We first show that this finding which we call "the sliding effect" is robust and
      easy to replicate for different orientations of the rectangular aperture (up to
      about 20 deg from vertical). This effect also occurs with an invisible circular
      aperture. In this case, using an adjustment task, observers have great difficulty
      extracting the actual direction of the feature (a gap or a dot on the line).
      Instead, a systematic bias towards the direction of "sliding" is observed. This
      misperception of the feature's velocity is markedly reduced or even suppressed
      when the circular aperture is outlined or when a visible circle is drawn around
      this invisible aperture. The line's perceived direction is always roughly
      orthogonal to the line's orientation regardless of the presence of a visible
      circular outline. This latter result is important because it shows that the
      feature on the line does not disambiguate the perpendicular signals extracted
      along the contour, even in conditions where this feature's motion is almost
      correctly perceived. Altogether, these results suggest that line-endings are not
      used by the visual system in the same way as a feature on the line when it comes
      to determining the line's perceived direction.

PMID- 9156216
TI  - Influence of luminance flicker and purity on heterochromatic brightness matching
      and hue discrimination: a postreceptoral opponent process.
AB  - We have studied psychophysically the characteristics of the postreceptoral stage
      of visual processing, using heterochromatic brightness matching (HBM) between 540
      and 600 nm, and hue discrimination between 565 and 585 nm, under differing
      luminance flicker (0-30 Hz) and excitation purity (1.0-0.1) conditions. The HBM
      curves exhibit deeper minima around 575 nm with decreasing purity. The minimum is
      generally most pronounced with a 3 Hz flicker and least pronounced with a 30 Hz
      flicker. Hue discrimination ability is relatively insensitive to flicker and
      deteriorates at the lower purities. The HBM results for low purities can be
      explained by the upper envelope of activities in PC- and MC-pathways.

PMID- 9156217
TI  - The spatial limit for motion detection in noise depends on element size, not on
      spatial frequency.
AB  - When a random spatial noise pattern is displaced for a short distance it seems to
      move coherently, but when the displacement exceeds a certain value, the direction
      of motion cannot be clearly perceived. We measured the displacement limit (Dmax)
      for a two-frame sequence and found that it depended on the size of the elements
      comprising the random pattern, even when low spatial frequencies were removed
      from the pattern by spatial band-pass filtering. Dmax depended strongly on
      contrast for the filtered patterns, but less so for the unaltered patterns. The
      data support a model for low level motion detection in which the maximum motion
      displacement that can be detected is determined by the mean separation of pattern
      elements, following a stage of low-pass spatial filtering, and in which the upper
      spatial displacement depends upon the pattern statistics, not upon the size of
      detectors in the visual system.

PMID- 9156218
TI  - Abnormal long-range spatial interactions in amblyopia.
AB  - Neural interactions between widely separated stimuli were explored with
      psychophysical and visual evoked potential (VEP) measures in normal and amblyopic
      observers. Contrast detection thresholds were measured psychophysically for small
      foveally viewed Gabor patches presented in isolation and in the presence of
      similar, but laterally displaced flanks. The amplitude and phase of VEPs elicited
      by similar targets were also measured. The presence of neural interaction between
      the target and flank responses was assessed by comparing the unflanked threshold
      to the flanked threshold in the psychophysical experiments and by comparing the
      response predicted by the algebraic sum of test and flank responses to that
      measured when test and flanks were presented simultaneously. In normal observers
      simultaneous presentation of test and flank targets produces a VEP response that
      is up to a factor of two larger than the linear prediction (facilitation).
      Psychophysical threshold is also facilitated by a comparable factor. Facilitation
      was found mainly for configurations in which local (carrier) and global (patch)
      orientations resulted in collinearity, independent of global orientation
      (meridian). Amblyopic observers showed several deviations from the normal
      pattern. The facilitation for the collinear configurations was either markedly
      lower than normal or was replaced by inhibition. The normal pattern of spatial
      interaction may facilitate the grouping of collinear line segments into smooth
      curves. In contrast, abnormal long-range spatial interactions may underlie the
      grouping disorders and perceptual distortions found in amblyopia.

PMID- 9156219
TI  - Motion-reversal reveals two motion mechanisms functioning in scotopic vision.
AB  - We studied scotopic motion mechanisms, using a two-frame sinusoidal grating
      separated by various ISIs equated for mean luminance level. Perceived direction
      of displacement varied with both ISI and luminance. As luminance decreased,
      apparent motion reversal disappeared. This is predicted by a first-order motion
      model if the underlying temporal impulse response function varies from biphasic
      under photopic conditions to monophasic under scotopic conditions. Performance at
      long (but not short) ISIs depends upon stimulus contrast, suggesting there is
      also a scotopic feature-tracking mechanism. With isoluminant and high spatial
      frequency gratings, where the temporal impulse response function is monophasic,
      no motion reversal was observed.

PMID- 9156220
TI  - The distance used for scaling disparities is the same as the one used for scaling
      retinal size.
AB  - To determine the physical size and global three-dimensional (3-D) shape of an
      object, retinal size and retinal disparity have to be scaled in accordance with
      the object's distance. We examined whether the distance used for scaling retinal
      disparity is the same as the distance used for scaling retinal size. Subjects
      adjusted the 3-D shape (size and depth) of a computer-simulated ellipsoid to
      match a tennis ball. Analysis of the errors when only the ellipsoid was visible
      in an otherwise completely dark room suggests that the distance used for scaling
      retinal disparity is indeed the same as that used for scaling retinal size. This
      was confirmed by showing that the correspondence between the distance used for
      scaling retinal disparity and that used for scaling retinal size does not improve
      when more information about distance is available (room lights on), although both
      distances are then much closer to the simulated distance. Finally, we show that
      this correspondence is not due to the use of distance-invariant higher order
      binocular information.

PMID- 9156221
TI  - Anisotropy for direction discrimination in a two-frame apparent motion display.
AB  - Direction discrimination (upward/downward or left/right) for a Gabor patch in a
      two-frame motion display was measured as a function of the inter-frame
      displacement size of the component grating with the stimulus position (center,
      left, right, upper and lower visual fields) as a parameter. The results showed
      that, for vertical motion in the center, left, right and lower visual fields, the
      observers saw downward motion more frequently than upward motion, whereas for
      vertical motion in the upper field and for horizontal motion, no preference for
      one of the two opposite directions was obtained. Human motion vision is
      anisotropic in the lower half of the visual field.

PMID- 9156222
TI  - The role of ocular muscle proprioception during modifications in smooth pursuit
      output.
AB  - The output of the smooth pursuit (SP) system can be increased by adding a portion
      of the recorded eye motion onto target motion, producing a situation analogous to
      that occurring with weakened ocular muscles. This change is most likely the
      result of alterations in the signals that code eye and target motion. We have
      assessed the contribution of one such signal, that arising from ocular
      proprioception, to the modification process during monocular SP by preventing the
      motion of the non-viewing eye with a suction scleral lens. The large increases
      normally observed for SP velocity following the modification period were
      substantially reduced under these conditions. Similar alterations were also
      observed in a manual tracking task. These results demonstrate that ocular
      proprioceptive signals serve to stabilize the output of the SP system following
      perturbations, via the recoding of eye and target motion.

PMID- 9156223
TI  - Extraretinal eye position signals determine perceived target location when they
      conflict with visual cues.
AB  - To examine the role of extraretinal eye position information (EEPI) in visual
      perception of target location in normal room illumination, subjects participated
      in experiments in which EEPI was manipulated using the eye press maneuver with
      either monocular or binocular viewing. The viewing condition and eye press caused
      EEPI and retinal information about target location to conflict. Pointing
      responses in eye press trials were all in the direction of EEPI showing that EEPI
      is the dominant source of information in egocentric visual space perception. In
      binocular viewing, version and vergence occur in response to the eye press to
      maintain fusion and EEPI based on these movements also determine perceived
      location. An unanticipated finding was that the eye press was variable in its
      effectiveness in rotating the eye, which contributed to large variability in
      pointing errors and suggested the method would be a poor choice for future work.

PMID- 9156224
TI  - Vertical eye position control in darkness: orbital position and body orientation
      interact to modulate drift velocity.
AB  - How stable is vertical eye-in-head position control in darkness when no visual
      targets are present? We evaluated this while varying both body-in-space
      orientation and eye-in-orbit position in six subjects who were free from
      oculomotor/vestibular disease. Vertical eye movements were monitored using a CCD
      video tracking system, and results were confirmed on one subject with the
      magnetic search coil. Three body orientations were used: (1) seated upright; (2)
      supine; and (3) prone. In each of these body orientations starting eye-in-orbit
      position was varied in quasi-random order from -20 to +20 deg, while vertical eye
      drift was monitored for a 90 sec period at each position. Subjects were
      instructed to hold their eyes as steady as possible. The relationship between
      body orientation/eye position and vertical eye drift velocity was examined using
      a linear regression technique. In contrast to prior clinical reports, normals
      exhibit a vertical nystagmus/drift in darkness. Moreover, slow-phase eye velocity
      was found to be dependent on eye-in-orbit position in the upright and supine body
      orientations. This pattern of eye drift mirrors Alexander's Law, with
      significantly increased drift velocities when subjects looked in the direction of
      their re-centering saccades (P < 0.05 or better). Body-in-space orientation also
      modulated the eye drift velocity, with significant differences in rate of eye
      drift (P < 0.05 or better) between extremes of body orientation (supine and
      prone) for five out of six subjects. The stability of the vertical oculomotor
      control system in the absence of visual input is strongly affected by body-in
      space orientation and eye-in-orbit position: manipulating either of these
      variables results in non-random patterns of drift. These results are discussed
      using a multiple-input model of vertical eye-in-head position control.

PMID- 9156225
TI  - L and M cone input into spectral sensitivity functions: a reanalysis.
AB  - In order to better understand the nature of long-wavelength (L) and middle
      wavelength (M) cone input into spectral sensitivity functions and determine the
      reliability with which it is possible to predict L:M cone inputs, we developed
      analytical methods to determine confidence intervals for L:M cone input for
      spectral sensitivity functions or data transformed to cone-contrast space.
      Spectral sensitivity functions measured by direct heterochromatic brightness
      matches are dominated by the L/M opponent channel over most of the spectral
      range. For detection of large/ long test stimuli, spectral sensitivity functions
      show a characteristic "notch" at the adapting wavelength, with the L/M opponent
      channel dominating most of the spectral range. Flicker increment threshold (FIT)
      spectral sensitivity functions display many of the characteristics of the
      luminance flicker mechanism described by Stromeyer et al. (1987). [Vision
      Research, 27, 1113-1137]. Previous modelling of FIT spectral sensitivity
      functions proposed a 2:1 L:M cone input for most of testing conditions. We show
      that FIT spectral sensitivity functions are dominated by L cones but show L cone
      suppression under bright red adapting fields. For the fitted spectral sensitivity
      functions or simulated data sets, we found small confidence intervals for L:M
      cone input into the L/M opponent channel and conclude that it is possible to
      reliably predict L:M cone input ratios. However, for similar data sets of
      additive spectral sensitivity functions, we found large confidence intervals for
      L:M cone input ratios and conclude that it is not possible reliably predict L:M
      cone input into the L/M non-opponent channel using available spectral sensitivity
      functions.

PMID- 9156226
TI  - Visual acuity and contrast sensitivity for individual Sloan letters.
AB  - Sloan letter optotypes are used frequently to evaluate visual impairment, and
      scoring procedures have been developed that are based on the numbers of letters
      that are identified correctly. However, previous studies have presented
      conflicting evidence regarding the relative identifiability of the individual
      Sloan letters. To investigate this issue further, we measured psychometric
      functions for the identification of each of the 10 Sloan letters, with individual
      letters presented in random order on the gray-scale display of a Macintosh
      computer-based testing system. Data were obtained from three visually normal
      subjects under each of three conditions: (1) as a function of log contrast at a
      relatively large letter size; (2) as a function of log contrast at a letter size
      near the acuity limit; and (3) as a function of log MAR (minimum angle of
      resolution) at maximum letter contrast. Estimates of threshold log contrast and
      threshold log MAR were derived from best-fitting Weibull functions. Threshold log
      contrast for small letters showed the greatest interletter variability. There was
      relatively little interletter variability in either threshold log contrast for
      large letters or threshold log MAR for high-contrast letters. However, due to the
      relatively steep psychometric functions under these latter two conditions, the
      different Sloan letters had considerably different percent correct values near
      threshold. The overall pattern of results suggests that the contrast sensitivity
      functions for individual Sloan letters are displaced laterally along a log MAR
      axis, while their vertical positions are essentially equivalent.

PMID- 9156227
TI  - Shift of equiluminance in congenital color vision deficiencies: pattern-ERG, VEP
      and psychophysical findings.
AB  - We compared electrophysiological responses [pattern-ERG (PERG) and VEP] and
      psychophysical measures to color stimuli to separate different forms of anomalous
      color vision. PERG and VEP were recorded from seven normals and 14 subjects with
      congenital color vision deficiencies. Stimuli were color checkerboards with 0.5
      deg check size, phase reversing at 34 rev/sec. The luminances of the red and
      green parts were varied in opposite direction from 0 to 30 cd/m2, while the hue
      of individual squares and space-averaged luminance were held constant. This
      allowed for one equiluminance condition where flicker appeared fused. In the
      seven normals, the subjective equiluminance was reached at a luminance ratio
      red/(red + green) = 0.50-0.53. At that point, the PERG amplitude was moderately,
      and the VEP amplitude sharply reduced. In 14 color anomalous subjects both the
      PERG and VEP were sharply reduced at equiluminance. These dips were shifted
      compared to normals and the dip position corresponded to the predicted luminance
      ratios obtained by calculations from L- and M-cone activation using the Smith
      Pokorny transformation. As we found a close correlation of the VEP-dip position
      and the anomalous quotient, these electrophysiological measures may allow
      objective assessment of color vision deficiencies.

PMID- 9156228
TI  - Relationship between pulmonary artery diameter at computed tomography and
      pulmonary artery pressures at right-sided heart catheterization. Massachusetts
      General Hospital Lung Transplantation Program.
AB  - RATIONALE AND OBJECTIVES: The purpose of the study was to determine the
      relationship between pulmonary artery (PA) size at computed tomography (CT) and
      PA pressures, to develop a noninvasive CT method of PA pressure measurement, and
      to determine a PA diameter that can enable differentiation of normal subjects
      from those with pulmonary hypertension. METHODS: PA vessel diameters in 55
      candidates for lung and heart-lung transplantation were measured at CT and
      correlated with PA pressures with both linear and stepwise multiple regression.
      The multiple regression equations were then tested prospectively in 35
      pretransplantation patients. RESULTS: Combined main and left main PA cross
      sectional area corrected for body surface area showed the best correlation with
      mean PA pressure (r = .87). The multiple regression equations helped predict mean
      PA pressure within 5 mm Hg in 50% of patients with chronic lung disease and in
      only 8% of patients with pulmonary vascular disease. CONCLUSION: There was a very
      good correlation between main and left main PA size and mean PA pressure. At
      present, however, CT has not demonstrated sufficient accuracy to be used
      clinically.

PMID- 9156229
TI  - Influence of visual distractors on detectability of liver nodules on contrast
      enhanced spiral computed tomography scans.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated the ability of observers to
      identify simulated nodules placed electronically on normal contrast material
      enhanced computed tomography (CT) scans of the liver to assess the effect of
      nodule size and polarity on detection and localization. METHODS: Seven readers
      evaluated two sets of CT scans that contained 80 stimuli each. The simulated
      nodules were either darker or brighter than the contrast-enhanced liver and were
      5.6-8.0 mm in diameter. Readers were asked to find the most suspicious-looking
      nodule on each section and rate the likelihood that the chosen location actually
      contained a nodule. RESULTS: The fraction of nodules found by each observer was
      substantially greater for dark nodules than for bright ones (0.679 +/- 0.03 vs
      0.345 +/- 0.045, respectively [mean +/- standard error]). This difference was
      consistent for all nodule sizes. Additional analyses (including receiver
      operating characteristic curves of conditional responses) suggested that the
      presence of bright blood vessels distracted the readers and decreased their
      ability to find bright nodules. CONCLUSION: Normal vascular structures on
      contrast-enhanced CT scans of the liver impair an observer's ability to detect
      bright liver nodules.

PMID- 9156230
TI  - Role of endothelium-derived nitric oxide-endothelin balance in contrast medium
      induced acute renal vasoconstriction in dogs.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated the involvement of nitric oxide
      and endothelin in radiographic contrast medium-induced changes in renal
      hemodynamics. METHODS: Eleven anesthetized healthy dogs were each studied during
      three periods. Thirty minutes before the first, second, and third periods, the
      dogs received 1 mL per kilogram of body weight of isotonic saline, L-N-nitro-L
      arginine-methyl-ester (L-Name, 10 mg/kg intravenously), and L-arginine (500 mg/
      kg intravenously), respectively. Renal blood flow (RBF) and mean arterial blood
      pressure were continuously monitored. The glomerular filtration rate (GFR) was
      evaluated by means of polyfructosan clearance. RESULTS: Contrast medium induced a
      significant (P < .05) decrease in RBF and GFR and a significant (P < .05)
      increase in urinary endothelin excretion. L-Name enhanced the effect of contrast
      media on RBF and GFR. L-arginine attenuated the effect of L-Name on the contrast
      medium-induced reduction of GFR. CONCLUSION: These findings support the
      hypothesis that acute contrast medium-induced intrarenal vasoconstriction may
      involve an imbalance of endothelial vasoactive agents, nitric oxide, and
      endothelin, and they confirm the involvement of hemodynamic changes in contrast
      medium-induced nephropathy.

PMID- 9156231
TI  - Combined videomanometric identification of abnormalities related to pharyngeal
      retention.
AB  - RATIONALE AND OBJECTIVES: The authors determined the usefulness of performing
      videoradiography and pharyngeal solid-state manometry during barium swallow in
      dysphagic patients with pharyngeal retention. METHODS: Results were
      retrospectively analyzed of simultaneous videoradiography and manometry
      examinations in 14 patients with retention of barium in the pharynx. Twelve age
      matched patients without retention served as a control group. RESULTS: Patients
      with retention regularly had less opening of the upper esophageal sphincter than
      patients without retention (7.6 vs 10.3 mm, respectively; P = .003). In patients
      with retention, the laryngeal elevation was lower (17.1 vs 23.8 mm, respectively;
      P = .001), and the resting pressure of the upper esophageal sphincter was
      significantly lower (42.4 vs 54.0 mm Hg, respectively; P = .04). The duration of
      upper esophageal sphincter relaxation was also shorter in patients with retention
      (374 vs 603 msec, respectively; P = .003). The peak pharyngeal contraction
      pressure was not significantly different. CONCLUSION: The constrictors play a
      minor role in the conveyance of the bolus through the pharynx. Pharyngeal
      shortening could be the most important mechanism in bolus transport.

PMID- 9156232
TI  - Intestinal absorption of Mn-mesoporphyrin in a small bowel sac system: effect of
      oleic acid.
AB  - RATIONALE AND OBJECTIVES: The authors investigated the effect of oleic acid (cis
      9-octadecenoic acid) (OA), a lipidic carrier, on the intestinal absorption rate
      and T1 relaxation time of manganese (III) mesoporphyrin (Mn-mesoporphyrin), a
      prototype hepatobiliary contrast agent for magnetic resonance imaging. METHODS:
      Mn-mesoporphyrin was formulated with OA at various concentrations. Small bowel
      sacs were created in 36 rats and filled with complexed and free Mn-mesoporphyrin.
      Intestinal absorption of Mn-mesoporphyrin was measured with spectrophotometry at
      364 nm. T1 relaxation times were measured in samples of Mn-mesoporphyrin
      solutions, bowel wall, liver, and bile. RESULTS: Absorption rates ranged from
      4.2%/cm2/h to 13%/cm2/h. Absorption was greatest (13%/cm2/h) when a combination
      of 1 mmol/L Mn-mesoporphyrin and 26.5 mmol/L OA was used. The T1 of bile
      decreased from 2,480 to 248 msec (maximum decrease) in rats that received Mn
      mesoporphyrin. CONCLUSION: Mn-mesoporphyrin is absorbed from the small bowel in
      both the lipid-associated and free form, resulting in substantial shortening of
      the T1 in bile.

PMID- 9156233
TI  - Technique for performing direct lymphangiography in pigs.
AB  - RATIONALE AND OBJECTIVES: The authors developed a porcine model for direct
      lymphangiography to be used as a reference for lymph node harvesting. METHODS: A
      pilot animal was studied first to develop the protocol, which was used
      successfully in 24 pigs. An indicator dye was first injected into each foot to
      make the lymphatic vessels visible. Then, ethiodized poppy seed oil was injected
      directly through cutdowns in both groins. Radiographs were obtained before and
      after lymph node harvesting. RESULTS: Images were of diagnostic quality in all
      animals. The pilot animal developed transient respiratory distress, which was
      thought to be due to the oil-based contrast material. The amount injected was
      reduced by half, and no episodes occurred thereafter in the study group. There
      were no other immediate or delayed complications. CONCLUSION: Direct
      lymphangiography is safe, easy, and reliable in a porcine model.

PMID- 9156234
TI  - Spiral computed tomographic colonography: determination of the central axis and
      digital unraveling of the colon.
AB  - RATIONALE AND OBJECTIVES: The authors developed and tested automated and
      semiautomated bowel-lumen tracking and colon-unraveling techniques for
      determining the central axis of the bowel. METHODS: A computer-simulated
      gastrointestinal tract phantom was used to test the accuracy of an automated
      algorithm for central axis determination and bowel unraveling. Variations in
      cross-sectional features between straight and unraveled formats were compared in
      a canine bowel segment in vitro and a human colon in vivo by using spiral
      computed tomography. Three readers each performed three semiautomated
      evaluations. RESULTS: Accuracy of the automated algorithm was confirmed by the
      high degree of correlation in the cross-sectional feature measurements (length
      error, < 1%). For the canine colon segment, accuracy of the semiautomated
      algorithm was confirmed by comparison with the automated tracing. For the human
      colon, readings were reproducible with 3.3% (+/- 1.9 standard deviation) mean
      variation in length. CONCLUSION: An automated algorithm for central axis
      deterioration and unraveling the colon has been validated in a gastrointestinal
      tract phantom. A semiautomated algorithm has been shown to be reproducible and
      time-efficient.

PMID- 9156235
TI  - Preparation of human whole lungs inflated and fixed for radiologic-pathologic
      correlation.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated a modified method of lung
      inflation and fixation for radiologic-pathologic correlation of lung disease.
      METHODS: Fifty-five whole human lungs obtained at autopsy were examined. Fifty
      lungs were cannulated via the main bronchus and distended with 20% formalin. The
      cannula was clamped for 15 minutes, 30 minutes, 2 hours, 2 days, 4 days, or 6
      days. Then the formalin was expelled with air at a pressure of 10 cm H2O. The
      lung was fixed with a mixture of polyethylene glycol 400, 95% ethyl alcohol, 40%
      formalin, and water. In the five lungs that were not cannulated, the formalin was
      expelled manually. RESULTS: The degree of inflation of 46 cannulated specimens
      was rated as good in 42, moderate in four, and poor in nine. Histologic
      preservation was not evaluated in 23 of 55 specimens because of postmortem
      autolysis. It was rated as good or moderate in 29 specimens. Both inflation and
      staining were rated as good in 21 specimens. CONCLUSION: This modified method of
      preparation of inflated, fixed lung provides good histologic preservation and
      radiographic appearance of lung.

PMID- 9156236
TI  - The "proper" binormal model: parametric receiver operating characteristic curve
      estimation with degenerate data.
AB  - RATIONALE AND OBJECTIVES: The authors assessed the use of a "proper" binormal
      model and a new algorithm for maximum-likelihood estimation of receiver operating
      characteristic (ROC) curves from degenerate data. METHODS: The proper binormal
      ROC model uses as its decision variable a monotonic transformation of the
      likelihood ratio that is associated with a pair of normal distributions, thereby
      ensuring fitted ROC curves with monotonic slope but maintaining a relationship
      with the conventional binormal model. A computer program entitled PROPROC was
      used to fit proper ROC curves to data obtained from computer-simulated and real
      observer studies. RESULTS: ROC indexes such as total area were estimated with
      PROPROC and compared with the corresponding values obtained from the conventional
      procedures. CONCLUSION: The proper binormal ROC model overcomes the problem of
      degeneracy in ROC curve fitting. PROPROC is highly robust and yields ROC
      estimates with less bias and greater precision than those obtained with the
      conventional binormal model.

PMID- 9156237
TI  - An introduction to academic radiology.
AB  - If you are a junior faculty member or are thinking of pursuing an academic career
      path, and you have read this far, you may be feeling somewhat overwhelmed. Keep
      all of this in perspective with your own personal goals and your "nonacademic"
      life outside the medical center. The multifaceted career of an academic
      radiologist may span 20-30 years or more. Whichever aspect of an academic career
      suits you best now may not be what suits you best 5 or 10 years from now. While
      you should be concentrating on the publication of manuscripts as an assistant
      professor, the other aspects, particularly administration and participation in
      organized radiology, may play a larger role in your career as you become more
      senior.

PMID- 9156238
TI  - Pulmonary abnormalities in a patient with chronic heart disease.

PMID- 9156239
TI  - Blood and marrow stem cell transplants in auto-immune disease: a consensus report
      written on behalf of the European League against Rheumatism (EULAR) and the
      European Group for Blood and Marrow Transplantation (EBMT)

PMID- 9156240
TI  - Autologous blood cell transplantation in B-CLL: response to chemotherapy prior to
      mobilization predicts the stem cell yield.
AB  - Successful stem cell mobilization and collection is possible in B-CLL after a
      favorable response to preceding chemotherapy, and also after treatment with the
      new nucleoside analogues fludarabine and cladribine. A poor response, on the
      other hand, seemed to predict a mobilization failure. CD34+ cell selection
      resulted in a 2- to 3-log reduction of the CLL cells in the harvests. Engraftment
      with both unselected and selected progenitor cells was rapid, and need for
      hospitalization was short. High-dose therapy with stem cell rescue appears to be
      capable of inducing CRs of high quality, but so far the follow-up is too short to
      define whether this will be translated into prolonged disease-free survival.

PMID- 9156241
TI  - Plasma levels of granulocyte colony-stimulating factor in patients after
      allogeneic bone marrow transplantation for chronic myeloid leukemia correlate
      with engraftment of transplanted marrow.
AB  - Granulocyte colony-stimulating factor (G-CSF) is considered to play a pivotal
      role in hemopoietic regulation. Its pharmacological application is reported to
      shorten chemotherapy-induced neutropenia as well as time to engraftment in
      patients after bone marrow transplantation (BMT). In order possibly to establish
      further rationale for G-CSF treatment strategies in patients undergoing BMT, we
      evaluated G-CSF plasma levels of 89 patients after allogeneic BMT for chronic
      myeloid leukemia (CML). EDTA anti-coagulated plasma samples were collected
      starting on day -1 (before grafting) and thereafter twice weekly for four
      consecutive weeks. G-CSF levels were estimated by enzyme immunoassay. Patients
      with late (> 30 days) bone marrow engraftment had consistently higher G-CSF
      levels at day +1 (after grafting) compared to patients with early (< or = 30
      days) engraftment, while all patients had low plasma levels on day -1/0. Mean G
      CSF plasma levels and time to engraftment were correlated (r = 0.79). In
      univariate analyses, high G-CSF levels at days +1, +4, +7, +10 and several
      clinical variables (such as TBI, unrelated donor transplant, state of disease)
      were predictive of late engraftment. Further analysis by multivariate Cox
      regression resulted in the following predictive model: high G-CSF plasma levels
      at day +7 and +10 (after grafting), in combination with a blastic phase of the
      disease were highly predictive of late engraftment. The significantly higher G
      CSF levels in patients with impaired engraftment may reflect early compensating
      mechanisms of the hemopoietic system, which should be investigated further.

PMID- 9156242
TI  - Induction, mobilization of peripheral blood stem cells (PBSC), high-dose
      chemotherapy and PBSC infusion in patients with untreated stage IV breast cancer:
      outcomes by intent to treat analyses.
AB  - We investigated the outcomes of patients with breast cancer undergoing induction
      chemotherapy, mobilization of peripheral blood stem cells (PBSC) and high-dose
      chemotherapy (HDC) with PBSC infusion. One hundred and fourteen patients with
      untreated stage IV breast cancer, with a median age of 46 years (range 24-62),
      were entered on a phase II trial consisting of; (1) doxorubicin, 5-flurouracil,
      methotrexate (AFM) x 4 courses at 2 week intervals; (2) cyclophosphamide (4
      g/m2), etoposide (600 mg/m2), cisplatin (105 mg/m2) (CEP), filgrastim (6
      micrograms/kg/day) and PBSC collection; (3) cyclophosphamide (6 g/m2), thiotepa
      (500 mg/m2), carboplatin (800 mg/m2), (CTCb) followed by PBSC infusion. All
      patients received AFM, 107 (94%) received CEP, 93 (82%) received CTCb and PBSC as
      per protocol and 99 (87%) ultimately received HDC and PBSC. There was one
      infectious death after AFM and all other deaths were associated with progressive
      disease. Fifty-two patients (46%) are alive, 21 (18%) without progression, at a
      median 31 months (range 22-47). The probabilities of survival and progression
      free survival at 3.5 years were 0.40 and 0.17, respectively. All 62 patients with
      visceral disease and/or a prior history of doxorubicin adjuvant therapy have
      relapsed or progressed. We conclude that the sequential administration of AFM,
      CEP and CTCb followed by PBSC resulted in long-term PFS only in patients who were
      NED, had bone-only disease or had lymph node or soft tissue disease with or
      without bone disease. Other strategies, aimed at improving responses to initial
      therapy, improving HDC regimens and/or developing immunomodulatory therapies,
      will be necessary to improve PFS for patients who fail doxorubicin adjuvant or
      who have visceral disease.

PMID- 9156243
TI  - Treatment-related mortality in 1000 consecutive patients receiving high-dose
      chemotherapy and peripheral blood progenitor cell transplantation in community
      cancer centers.
AB  - High-dose chemotherapy (HDC) with autologous peripheral blood progenitor cell
      (PBPC) is being increasingly utilized as a therapeutic modality for patients with
      chemotherapy-sensitive disease. Several published HDC regimens have become
      relatively widely used. The purpose of this analysis was to determine treatment
      related mortality (TRM) following administration of five different HDC regimens
      in community cancer centers. A retrospective evaluation of 1000 consecutive
      patients with leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple
      myeloma, sarcoma, ovarian cancer, or breast cancer who received one of five
      published HDC regimens followed by PBPC infusion over a 5-year period in
      community cancer centers was performed to determine TRM. Fifty-nine patients
      (5.9%) died within 100 days of PBPC infusion. Twenty-five patients (2.5%) died
      predominantly of causes related to disease progression. Thirty-four patients
      (3.4%) died of TRM, 15 patients (1.5%) died from infection and 19 (1.9%) died
      from regimen-related toxicities (RRT). In a logistic model, increasing age (P =
      0.001) and lower numbers of CD34+ cells/kg (P = 0.003) were associated with an
      increased risk of 100-day TRM. High-dose cyclophosphamide, thiotepa, and
      carboplatin was associated with a lower risk of mortality than other regimens (P
      = 0.0001). High-dose chemotherapy and autologous PBPC support can be performed in
      community cancer centers with relative safety. Patient age, the type of
      preparative regimen and the number of CD34+ cells infused were important
      determinates of mortality.

PMID- 9156244
TI  - Absence of detectable PML-RAR alpha fusion transcripts in long-term remission
      patients after BMT for acute promyelocytic leukemia.
AB  - Twenty patients with APL in long-term remission after BMT were analyzed for the
      presence of the PML-RAR alpha fusion gene by RT-PCR. Ten patients had undergone
      autologous BMT (six of them peripheral blood stem cell transplantation) and 10
      allogeneic BMT. A total of 60 samples were examined by two different protocols.
      Of the eight patients studied just before conditioning, five showed PML-RAR alpha
      transcript prior to transplantation. Three of them were in CR and became PCR
      negative early post-transplantation. The other two patients, that were not in CR
      before transplant, remained PCR positive, relapsed early post-transplant and
      died. In the remaining patients no PML-RAR alpha transcripts were visible
      throughout their post-BMT courses. Our data show that long-term remission after
      BMT in APL patients is associated with eradication of cells carrying the PML-RAR
      alpha transcript, and that continued positivity of this test predicts subsequent
      relapse. The fact of the disappearance of PML-RAR alpha transcript early after
      BMT in patients previously positive suggest that transplant is capable of curing
      APL mainly through antileukemic action of the conditioning regimen and therefore,
      transplantation must be indicated in CR patients if a positive RT-PCR remains
      after treatment with ATRA plus chemotherapy.

PMID- 9156245
TI  - Disseminated toxoplasmosis in marrow recipients: a report of three cases and a
      review of the literature. Bone Marrow Transplant Team.
AB  - Toxoplasma infection following bone marrow transplantation (BMT) is infrequently
      reported. We report three cases of disseminated toxoplasmosis in BMT recipients
      documented during an 8-year period at our institution: one after an unrelated
      marrow transplant in a toxoplasma-seronegative patient, the second complicating
      syngeneic marrow transplantation, and the third following allogeneic, related
      BMT. The disease is extremely rare in seronegative patients and has not been
      previously reported in syngeneic recipients. Toxoplasmosis was diagnosed at
      autopsy in two of the three cases. We also present a review of all reported cases
      of toxoplasmosis in marrow recipients from North American and other BMT centers.
      Heightened awareness of the occurrence of toxoplasmosis in marrow recipients and
      early diagnostic/therapeutic measures are needed for a better outcome.

PMID- 9156246
TI  - Decreased interleukin 10 and increased interferon-gamma production in patients
      with chronic graft-versus-host disease after allogeneic bone marrow
      transplantation.
AB  - Ex vivo production of interleukin 10 (IL-10) and interferon-gamma (IFN-gamma) was
      investigated in patients with (n = 5) or without (n = 5) chronic graft-versus
      host disease (cGVHD) after allogeneic BMT. Patients were matched for time after
      transplantation and type of transplant. Anti-CD3-induced IL-10 production in MNCs
      isolated from patients with cGVHD (range/median: 26-650 pg/10(6) MNC; 400
      pg/10(6) MNC) was significantly reduced compared to patients without cGVHD (646
      2662 pg/10(6) MNC; 1314 pg/10(6) MNC; P < 0.05) or healthy controls (679-6361
      pg/10(6) MNC; 3054 pg/10(6) MNC, P < 0.01). In vitro inhibition of IL-10 by an
      anti-IL-10 monoclonal antibody enhanced the release of IFN-gamma by anti-CD3
      stimulated MNCs from 354 +/- 34 pg/10(6) MNCs to 899 +/- 61 pg/10(6) MNCs. Thus,
      low IL-10 production may cause high IFN-gamma release. In anti-CD3-activated MNCs
      obtained from patients with cGVHD IFN-gamma production was significantly
      increased (324-3331 pg/10(6) MNC; 1849 pg/10(6) MNC) compared to healthy donors
      (127-900 pg/10(6) MNC; 305 pg/10(6) MNC P < 0.01). In addition, median IFN-gamma
      release by anti-CD3-activated MNCs obtained from patients without cGVHD (464
      pg/10(6) MNC) was about five-fold lower than in patients with cGVHD. In contrast
      to cytokine production, the differential leukocyte count (percentages of
      monocytes, T cells and CD4/CD8 ratio) was essentially the same both in patients
      with or without cGVHD. Thus, a different activation of Th-1 and Th-2 cells by
      anti-CD3 may be responsible for the deviant cytokine productions in patients with
      cGVHD. In conclusion, we observed significantly decreased IL-10 production in
      patinets with cGVHD and an increased median IFN-gamma secretion, which may
      contribute to the altered cytokine production after allogeneic BMT leading to
      cGVHD. Thus, supplementing IL-10 may become a new strategy for preventing cGVHD.

PMID- 9156247
TI  - Mixed hematopoietic chimerism after allogeneic bone marrow transplantation: the
      impact of quantitative PCR analysis for prediction of relapse and graft rejection
      in children.
AB  - It still remains unclear whether patients with mixed hematopoietic chimerism (MC)
      after allogeneic bone marrow transplantation (allo-BMT) have an increased risk of
      developing relapse or graft failure. To address this question, we monitored the
      individual dynamics of chimerism after allo-BMT in pediatric patients within a
      prospective case control study. The individual ratio of donor to recipient
      peripheral white cells was determined by quantification of genomic variable
      number of tandem repeats (VNTRs) with a polymerase chain reaction (PCR) approach.
      Within the study period from 1 January 1994 until 1 July 1996 we investigated 50
      sequences of 46 pediatric patients after allo-BMT (32 with malignant, 18 with
      nonmalignant diseases). We found complete chimerism (CC) in 34/50 cases, MC in
      12/50 follow-ups and 4/50 patients revealed autologous recovery (AC). Eight of 12
      patients with MC showed increasing autologous patterns and subsequently relapsed
      or rejected their graft, 3/12 decreasing amounts of recipient DNA and turned to
      CC upon further follow-up. One patient of 12 who had severe combined
      immunodeficiency (SCID), attained engraftment with a stable MC pattern. Three
      patients of 34 with CC relapsed lacking a transitional MC interval. However, the
      time span between last CC confirmation and relapse in each of these three
      patients was 6 months or longer. We suggest that these patients also developed a
      stage of transitional MC but that the critical timepoint of molecular
      confirmation by PCR was missed as time intervals in the individual follow-up of
      these three patients were too long (> or = 6 months). In summary, the results
      demonstrate that the individual risk of developing relapse or graft failure is
      significantly enhanced in the MC situation (P < 0.0005). Therefore the
      quantitative analysis of MC at short time intervals might be of great value to
      identify high risk patients which will have a significantly/enhanced risk for
      relapse or graft rejection.

PMID- 9156248
TI  - Sequential molecular monitoring of chimerism in chronic myeloid leukemia patients
      receiving donor lymphocyte transfusion for relapse after bone marrow
      transplantation.
AB  - Recent observations of chimerism in patients relapsed following an allotransplant
      suggest the persistence of immunotolerance, thus offering a biologic rationale
      for the use of donor lymphocyte transfusion (DLT). In this study, we have
      analyzed by PCR amplification of several VNTR regions, sequential bone marrow and
      peripheral blood DNA samples in four patients who received DLT for CML relapse
      after bone marrow transplantation. Prior to DLT, all patients showed mixed
      chimerism in peripheral blood cells while two had mixed chimerism and two no
      chimerism in the BM. None of these four patients showed evidence of chimerism at
      the cytogenetic level (all had 100% +ve metaphases). After DLT, a complete
      hematologic and molecular remission (ie disappearance of the BCR/ABL fusion
      transcript) was obtained in the two patients who had bone marrow mixed chimerism
      prior to DLT. The two patients without evidence of marrow chimerism prior to DLT
      converted to a pattern of mixed chimerism after DLT, but both developed a severe
      bone marrow aplasia occurring at day 56 and 36, respectively. With regard to the
      sequential analysis of bone marrow chimerism after DLT we observed that: (1) the
      disappearance of BCR/ABL +ve cells paralleled the conversion to a pattern of full
      donor chimerism; and (2) the time interval to achieve CR was inversely correlated
      with the percentage of donor DNA in bone marrow. In conclusion, we have shown
      here that the assessment of bone marrow pre-DLT chimerism by PCR analysis might
      predict the response in patients with favorable characteristics, and also might
      identify patients at high risk of developing severe myelosuppression.

PMID- 9156249
TI  - Outcome of acute leukemia relapsing after bone marrow transplantation: utility of
      second transplants and adoptive immunotherapy.
AB  - We studied 231 acute leukemia patients relapsing after allogeneic (n = 114) or
      autologous (n = 117) BMT to assess the outcome of further therapy. In general,
      all patients in good condition were eligible for second transplants except for
      post-allograft relapses from 1993-1994 onwards who received cytokine- or cell
      mediated immunotherapy. The major reason for patients not progressing to second
      graft was death from progressive disease or toxicity of salvage chemotherapy.
      Seventeen of 231 patients (7%) were alive at the last follow-up. Six of 14 post
      autograft relapses treated with second transplants were alive and well, compared
      with five of 103 not undergoing second grafts (P < 0.0001). One of 23 post
      allograft recipients treated with second allografts was alive with an
      extramedullary relapse, compared with five of 13 receiving immunotherapy and none
      of 78 receiving standard-dose or palliative therapy (P < 0.0001). We conclude
      that only a small proportion of highly selected acute leukemia patients relapsing
      after a transplant reach the stage of a conventional second transplant. In our
      experience, second allografts after myeloablative therapy in patients relapsing
      after one allograft are associated with very poor results, and immunotherapy may
      be a better approach in such cases. Selected patients relapsing after an
      autograft may become long-term survivors following a second autograft or an
      allograft.

PMID- 9156250
TI  - Enhanced graft-versus-host disease in older recipient mice following allogeneic
      bone marrow transplantation.
AB  - The incidence and severity of GVHD following bone marrow transplantation
      increases with recipient age. The role of recipient age on the development of
      GVHD was analyzed in a semi-allogeneic (C57BL/6-->(C57BL/6 x DBA/2)F1) murine
      GVHD system. Young adult (2 months) and old (12-14 months) recipient mice were
      lethally irradiated and reconstituted with young adult T cell-depleted bone
      marrow (ATBM) or ATBM and young spleen cells. A significantly higher percentage
      of old vs young recipients developed lethal GVHD. Furthermore, while pre
      transplant conditioning with irradiation was not required to observe increased
      mortality in old recipients, irradiation predisposed the older animals for a more
      severe course of GVHD, suggesting that GVHD occurred in old compared to young
      animals in the absence of pre-transplant conditioning but was exacerbated by
      irradiation. Histologically, the immunological responses in the GVHD target
      organs were more severe in the old GVHD animals. In support of this observation,
      increased spontaneous proliferation was observed using lymphoid cells isolated
      from old vs young GVHD mice. These findings demonstrate that old recipients
      develop a more severe course of GVHD following BMT, and may present a unique
      opportunity to study age-related factors in the generation of GVHD.

PMID- 9156251
TI  - Noncontinuous use of angiotensin converting enzyme inhibitors in the treatment of
      experimental bone marrow transplant nephropathy.
AB  - Angiotensin-converting enzyme (ACE) inhibitors can be used to prevent the
      development of radiation nephropathy after BMT. In previous BMT nephropathy
      studies, ACE inhibitor therapy was started pre-BMT and continued indefinitely. In
      preparation for clinical trials, studies were designed to determine whether
      effective prophylaxis could be achieved if ACE inhibitor therapy was started
      after engraftment, and to determine whether ACE inhibitors needed to be given
      indefinitely. The present studies in our rat syngeneic BMT model showed that
      captopril therapy started 25 days post-BMT was as effective as therapy started
      prior to BMT. When ACE inhibitor therapy was discontinued 28 weeks after BMT, the
      protective effect was not lost if adequate control of azotemia had been
      maintained for 26 weeks. If adequate control of azotemia was not maintained for
      26 weeks, BMT nephropathy progressed rapidly when ACE inhibitor therapy ended,
      and slowly when it was continued. Failure to control azotemia was a better
      predictor of renal failure than failure to control hypertension or proteinuria.
      Based on these preclinical studies, it would appear that ACE inhibitor therapy
      will be effective in the prophylaxis of BMT nephropathy even if begun after
      engraftment, and that ACE inhibitors may not need to be given indefinitely.

PMID- 9156252
TI  - Fatal GVHD demonstrating an involvement of respiratory muscle following donor
      leukocyte transfusion (DLT).
AB  - A 41-year-old female patient with AML, who relapsed after an allogeneic BMT from
      her HLA-identical sister, was treated by a donor leukocyte transfusion (DLT).
      Thereafter, bone marrow aplasia accompanied by the disappearance of leukemic
      blasts following the GVHD was observed. The patient died of chronic GVHD with
      respiratory muscle involvement 19 months after the DLT. Although the DLT was
      considered helpful in suppressing the proliferation of the leukemic cells, it
      might also have caused the severe GVHD observed in this case. Efforts to separate
      the lymphocyte clones responsible for GVL from those for the GVHD thus appear to
      be necessary for the further development of the therapeutic approach, so-called
      DLT.

PMID- 9156253
TI  - Allogeneic bone marrow transplantation for hypereosinophilic syndrome with
      advanced myelofibrosis.
AB  - A 33-year-old man with an atypical course of hypereosinophilic syndrome including
      malignant hypercalcemia, osteolytic lesions and evolution into severe
      myelofibrosis was treated by allogeneic bone marrow transplantation after
      conditioning with cytoxan and total body irradiation. As the transplant was sex
      mismatched, chimerism was studied by means of cytogenetic analysis and Y
      chromosomal DNA amplification by PCR assay. Long-term complete remission has been
      assessed by normalization of blood cell counts, magnetic resonance imaging and
      karyotypic analysis. A relapse was observed 40 months after transplantation. The
      patient remains alive 44 months post-BMT. This case report is compared with those
      reported in the literature.

PMID- 9156254
TI  - Multiple autoimmune events after autologous bone marrow transplantation.
AB  - A 36-year-old woman with RAEB-t and severe bone marrow fibrosis undergoing
      autologous BMT, developed a histologically documented GVHD-like skin rash.
      Thereafter, autoimmune thyroiditis, autoimmune thrombocytopenic purpura and
      autoimmune hemolytic anemia and a lupus anti-coagulant (LAC) were diagnosed. The
      patient is still alive, symptom-free and in first complete remission (CR);
      however, all of the autoantibodies are still detectable, with the exception being
      the anti-erythrocyte antibody. The most outstanding feature of the present case
      is the polymorphism of the autoimmune events, in the absence of a coexisting
      systemic autoimmune disease. This patient has achieved long-term disease-free
      survival (DFS) in first CR despite high-risk MDS and the repeated
      immunosuppressant therapy required because of the complications described above;
      a GVL reaction somewhat similar to the autoimmune events may have contributed
      towards maintaining disease control.

PMID- 9156255
TI  - Anaphylaxis during autologous peripheral blood progenitor cell infusion.
AB  - Anaphylaxis has been reported in subjects receiving peripheral blood precursor
      cell (PBPC) infusions; however the etiologic agent is unclear. Basophils from a
      PBPC-allergic subject were challenged with each individual component of the stem
      cell infusion and with recombinant human (rh)DNAse. Histamine release data were
      compared with those using basophils from control subjects. Histamine release
      assays were repeated using basophils from a control subject passively sensitized
      with serum IgE from the patient. Skin testing with bovine DNAse was performed
      using standard techniques. Basophil histamine release occurred in the patient,
      but not in controls, with bovine DNAse. No release could be provoked by any of
      the other components of the infusate; no release could be detected with rhDNAse.
      Sensitivity to bovine DNAse could be transferred to basophils from a control
      subject with the serum IgE from the patient. Marked epicutaneous skin test
      reactivity to bovine DNAse was evident in the patient, but not in control
      subjects. We conclude that systemic reactions during peripheral blood precursor
      cell infusions may represent true IgE-mediated anaphylaxis to bovine DNAse in the
      infusate. Skin testing can detect such sensitivity, and the use of rhDNAse may
      obviate such reactions.

PMID- 9156256
TI  - Neosartorya fischeri: an invasive fungal pathogen in an allogeneic bone marrow
      transplant patient.
AB  - Invasive fungal infections are a complication of allogeneic BMT. We report the
      first case of a Neosartorya fischeri fungal infection in a patient following
      allogeneic BMT. Neosartorya fischeri is related to Aspergillus fumigatus, but it
      is a distinct fungal species. Despite granulocytic engraftment and aggressive
      anti-fungal therapy with amphotericin B, the patient died of overwhelming fungal
      infection on day 60 post-BMT. Neosartorya fischeri is a pathogen that grows
      slowly in culture which can delay or confuse identification. This case further
      supports the need for more effective prophylaxis and treatment of non-Candida
      fungal infections in the allogeneic BMT population.

PMID- 9156257
TI  - CD34 is not expressed on the cells of chronic lymphoproliferative disorders or in
      the vast majority of non-Hodgkin's lymphomas: a review of 1573 cases.

PMID- 9156258
TI  - Partially mismatched blood cell transplants for high-risk hematologic malignancy.
AB  - Eleven patients with high-risk hematologic malignancy received cryopreserved but
      otherwise unmanipulated blood cell transplants (BCT) from partially mismatched
      family members in whom progenitor cells had been mobilized by G-CSF. Donors were
      mismatched by up to one antigen in the GVH direction and up to three antigens in
      the rejection direction. Outcomes were compared with those of 22 patients
      receiving BCT from fully matched donors. Two mismatched patients died without
      engraftment on day 21 and 32. One had rejected bone marrow from the same donor,
      the other was mismatched by two antigens in the rejection direction and received
      the lowest dose of CD34+ cells. Median time to granulocyte engraftment was 21.5
      (range 16-33) days for the mismatched group compared with 16 (11-28) days for the
      matched group (P = 0.01). No correlation was found between CD34+ cell dose and
      time to granulocyte or platelet recovery. In the mismatched and matched BCT
      groups respectively, the risk of grade II-IV acute graft-versus-host disease
      (GVHD) was 73% vs 28% (P = 0.001) and of chronic GVHD 100% vs 78% at 18 months (P
      = 0.01). The relationship of T cell dose to acute GVHD could only be evaluated in
      the matched group and no correlation was found. One of 11 mismatched patients and
      eight of 22 matched patients had relapse or persistent disease. Disease-free
      survival at 1 year was similar at 55% for mismatched and 50% for matched BCT.
      These results indicate that allogeneic BCT from partially mismatched family
      members is accompanied by a high incidence of GVHD but may result in comparable
      survival to BCT from fully matched donors.

PMID- 9156259
TI  - Interleukin-12 induced cytolytic activity in lymphocytes from recipients of
      autologous and allogeneic stem cell transplants.
AB  - Interleukin-12 (IL-12) has been reported to enhance the cytolytic activity of NK
      and activated T cells and to induce low levels of lymphokine-activated killer
      (LAK) activity in normal human lymphocytes. Therapy with IL-12 has induced tumor
      eradication in murine models. These observations suggest that IL-12 might have a
      role as treatment for minimal residual disease following transplantation. To
      determine whether PBL from recipients of autologous (autoSCT) and allogeneic
      (alloSCT) bone marrow or peripheral blood stem cell transplants respond to IL-12
      with generation of LAK activity, PBL were incubated with IL-12 for 5 days, then
      tested in a 51Cr release assay for lysis of Daudi. PBL from 17 normal 'control'
      individuals were similarly tested and lysis was observed in only 3/17 (mean 16.9%
      of the three). By contrast, PBL from 10/12 patients obtained a median of 30 days
      after autoSCT, exhibited significant IL-12-induced LAK activity (mean lysis,
      35.3%, P < 0.005 vs controls). PBL from 18 of 20 patients tested a median of 44
      days after alloSCT also exhibited significant LAK activity (mean lysis, 30.0%, P
      < 0.005 vs controls). In autoSCT recipients, IL-12 and IL-2 at high
      concentrations (1000 U/ml each) were additive for induction of LAK activity,
      whereas low, suboptimal concentration of IL-12 (250 U/ml) and IL-2 (1 U/ml) were
      synergistic in 3/5 experiments. The percentage of PBL expressing IL-12 receptor
      beta 1 chain (IL-12r beta 1) was higher in stem cell recipients than in normal
      individuals, P < 0.05. Moreover, a higher percentage of IL-12r beta 1-positive
      PBL was associated with greater IL-12-induced LAK activity in transplant
      recipients. These studies demonstrate that PBL obtained early after stem cell
      transplantation have a higher percentage of cells expressing IL-12r beta 1 and
      respond to IL-12 with significantly greater LAK cytotoxicity than PBL from normal
      controls. These results suggest that IL-12 is a potentially attractive candidate
      for study as consolidative immunotherapy after stem cell transplantation.

PMID- 9156260
TI  - Early allogeneic transplantation favorably influences the outcome of adult
      patients suffering from acute myeloid leukemia. Societe Francaise de Greffe de
      Moelle (SFGM).
AB  - Allogeneic BMT for patients with acute myeloid leukemia (AML) is presently a
      reference therapy. The indications for this therapy mainly rely upon prognostic
      factors, and their importance is constantly reassessed. To examine the impact of
      time from diagnosis to transplant on survival and leukemia-free survival (LFS),
      we analyzed 109 patients from the database of the SFGM comprising patients who
      had all received an HLA-identical allogeneic BMT for a diagnosis of AML in first
      complete remission (CR1) between January 1987 and December 1992. All patients
      were conditioned with cyclophosphamide (CY) and total body irradiation (TBI)
      (CYTBI), and methotrexate (MTX) + cyclosporin A (CsA) were used as graft-versus
      host disease (GVHD) prophylaxis. Patient characteristics were: age = 33 +/- 9,
      M/F = 64/45, white blood cell count (WBC) at diagnosis = 27 +/- 42 x 10(9)/l, FAB
      distribution: M1 and M2 = 55; M3 = 15, M4 and M5 = 33, M0, M6 and M7 = 6.
      Karyotyping was carried out for 64 patients: 32 had a normal karyotype, 16 had
      good prognosis abnormalities (t(8;21), t(15;17), inv 16) and 16 patients had
      other abnormalities. Eleven patients needed two courses of induction to achieve
      CR. Time between diagnosis and BMT was 120 (64-287) days. Forty-nine patients
      developed grade > or = 2 acute GVHD (actuarial probability = 46%). With a median
      follow-up of 50 months (27-100), the 5-year probabilities for transplant-related
      mortality (TRM), relapse, overall survival and LFS are respectively 25%, 26%, 59%
      and 55%. A multivariate analysis showed that survival is adversely influenced by
      three independent factors: time to transplant (> 120 days vs < or = 120 days),
      acute GVHD (grade 2-4 vs grade 0-1) and age (> 33 vs < or = 33). LFS is only
      influenced by the first two of these factors. The favorable impact of a shorter
      time from diagnosis to transplant should lead to performing the transplant as
      early as possible. Practically speaking, this means that when such therapy is
      chosen for a patient with CR1 AML, the search for an allogeneic donor should
      begin immediately and transplant be performed as soon as possible.

PMID- 9156261
TI  - Autotransplantation for relapsed or refractory non-Hodgkin's lymphoma (NHL): long
      term follow-up and analysis of prognostic factors.
AB  - One hundred and thirty-six patients autografted for relapsed or refractory non
      Hodgkin's lymphoma (NHL) were evaluated to assess long-term event-free survival
      and to identify important prognostic factors. High-dose therapy consisted
      primarily of carmustine (BCNU), etoposide, cytarabine, and cyclophosphamide
      (BEAC) followed by unpurged autologous stem cell rescue. The 5-year Kaplan-Meier
      event-free survival (EFS) for the entire cohort was 34% (95% confidence interval:
      24-44%) with a median follow-up of approximately 3 years (range 0-7.5 years). For
      patients entering with minimal disease (defined as all areas < or = 2 cm), the 5
      year EFS was 40 vs 26% for those entering with bulky disease (P = 0.0004). In the
      multivariate analysis, minimal disease on entry and administration of involved
      field XRT post-transplant were significantly associated with improved EFS; the
      latter association was observed mainly in the cohort of patients with bulky
      disease. The overall 100-day treatment-related mortality rate was 4.4% (3% for
      the last 71 patients). New strategies are needed to reduce the high rate of
      relapse (50-60%) following auto-transplantation for relapsed or refractory NHL.

PMID- 9156262
TI  - The in vitro detection of anti-leukaemia-specific cytotoxicity after autologous
      bone marrow transplantation for acute leukaemia.
AB  - Anti-leukaemia activity after allogeneic bone marrow transplantation has been
      studied extensively but its antigen specificity and effector cell phenotype
      remain unknown. Here we report a study in three recipients of autologous bone
      marrow transplantation done as part of the treatment for acute leukaemia, in whom
      we were able to detect innate specific anti-leukaemia activity post-transplant.
      One patient maintained selective cell-mediated cytolytic activity against her
      autologous leukaemic cells in the absence of cytolysis of her normal bone marrow
      mononuclear cells (BMMC). She remains in complete remission 3 years after ABMT
      for acute myeloid leukaemia (M5). A second patient was transplanted for acute
      lymphoblastic leukaemia and had detectable anti-leukaemia activity up to 20 weeks
      post-ABMT. At this point anti-leukaemia activity could no longer be demonstrated
      and the patient suffered a relapse 2 weeks later. A third patient was
      transplanted for AML (M4 Eo) and lacked detectable leukaemia-specific immune
      reactivity at 1, 3 and 6 months post-ABMT. She relapsed 6 months after her ABMT
      and returned to complete remission after further chemotherapy. She commenced
      treatment with alpha interferon and regained NK function. Furthermore, she
      developed high level cytolytic activity against her autologous leukaemic cells in
      the absence of activity against her remission bone marrow samples. She remains in
      complete remission 17 months after her initial relapse. This is the first report
      of an apparent association between in vitro leukaemia-specific cytolytic activity
      in individual patients after ABMT and clinical outcome. It encourages the theory
      that autologous immunomodulation may be useful in the future treatment of
      leukaemia.

PMID- 9156263
TI  - Preferential usage of T cell receptor (TCR) V beta by allogeneic T cells
      recognizing myeloid leukemia cells: implications for separating graft-versus
      leukemia effect from graft-versus-host disease.
AB  - New understanding of the alloresponse following bone marrow transplantation
      supports the possibility that the graft-versus-host disease (GVHD) response can
      be separated from a favorable graft-versus-leukemia (GVL) effect. We used chronic
      myeloid leukemia (CML) cells to generate 122 recipient-reactive T cell clones
      from a closely HLA-matched sibling responder. Clones were tested for their
      proliferative response to stimulator CML cells or PHA-transformed (non-leukemic)
      lymphoblasts. Of 78 clones tested, 32 recognized both leukemia cells and PHA
      blasts, 19 only CML and four only PHA blasts. The remainder were non-specific
      responders. This functional specificity corresponded to distinct patterns of T
      cell receptor (TCR) V beta usage: clones recognizing CML cells preferentially
      used V beta 5, V beta 6/7 while clones recognizing both CML and PHA blasts or
      only PHA blasts preferentially used V beta 3 and V beta 8. It may therefore be
      possible to identify in vitro-generated myeloid leukemia-restricted donor T cells
      by their pattern of V beta usage. TCR V beta antibodies could thus be used to
      select and expand leukemia-restricted donor T cells for transfusion after BMT to
      specifically enhance the GVL response.

PMID- 9156264
TI  - Ribavirin therapy in bone marrow transplant recipients with viral respiratory
      tract infections.
AB  - Treatment with ribavirin was instituted in 12 allogeneic and one autologous bone
      marrow transplant (BMT) recipients with proven respiratory syncytial virus (RSV),
      influenza B virus or parainfluenza virus infections. RSV was diagnosed in six
      cases, influenza B virus in four and parainfluenza virus in three patients.
      Ribavirin was given orally or intravenously (15-20 mg/kg/day in three divided
      doses) and in nine cases with the addition of ribavirin inhalations (6 g/day).
      Three patients required ventilator support. Three out of seven patients with
      pneumonia, including one patient with RSV who developed pulmonary infiltrates 10
      days after the start of therapy, died despite treatment with ribavirin (two RSV,
      one influenza B). Multiple etiological agents were found in the fatal cases. The
      clinical condition improved in 10 of 13 patients during therapy. No serious
      adverse effects of systemic ribavirin were noticed. Two patients had reversible
      signs of hemolysis but only one patients required more erythrocyte transfusions
      than expected after BMT. Obstructive respiratory distress was often observed (6/9
      patients receiving ribavirin inhalation therapy), which resulted in
      discontinuation of aerosolized therapy in four cases. Time to engraftment (WBC <
      0.2 x 10(9)/l) did not differ from other non-treated BMT patients. We conclude
      that ribavirin is well tolerated both orally and intravenously and it may, if
      instituted before development of hypoxia, reduce morbidity and mortality of RSV,
      influenza B and parainfluenza in this group of patients.

PMID- 9156265
TI  - Endothelial cell markers in bone marrow transplant recipients with and without
      acute graft-versus-host disease.
AB  - To investigate endothelial cell alterations in BMT recipients developing acute
      graft-versus-host disease (aGVHD) we determined levels of the endothelial cell
      markers von Willebrand factor (VWF) and thrombomodulin (TM) in 57 patients
      undergoing BMT. Before conditioning VWF and TM levels did not differ
      significantly between transplant recipients who later developed no or mild (grade
      I) aGVHD (group A, allogeneic n = 22, autologous n = 7; VWF 136.0 +/- 44.1%; TM
      29.5 +/- 18.0 ng/ml), and those with moderate or severe (grade II or III) aGVHD
      (group B, n = 28; VWF 142.2 +/- 37.6%; TM 35.2 +/- 20.1 ng/ml). A first
      significant rise of both VWF and TM level was noted after conditioning (day 0)
      both in group A (VWF 197.0 +/- 113.3%; P < 0.001; TM 39.3 +/- 23.3 ng/ml; P <
      0.01) as well as in group B (VWF 201.7 +/- 53.3%; P < 0.0001; TM 43.5 +/- 23.5
      ng/ml; P < 0.05). Subgroup analysis of autografted patients revealed no
      significant increase after conditioning in these patients. At the time of
      engraftment and onset of aGVHD (day 21), when VWF and TM levels within the groups
      were significantly elevated as compared with baseline (day -8) levels, group B
      patients (62.7 +/- 38.5 ng/ml) had significantly higher (P < 0.01) TM levels than
      patients of group A (37.4 +/- 19.6 ng/ml). This significant elevation also
      persisted at the end of the investigational period (day 28; group B: 56.0 +/-
      37.6 ng/ml; group A: 38.2 +/- 23.7 ng/ml; P < 0.01). An elevation of endothelial
      cell markers is found in the course of BMT, particularly after conditioning and
      at the time of engraftment. This increase is pronounced in patients with aGVHD
      suggesting not only epithelial cell but also endothelial cell injury during
      aGVHD.

PMID- 9156266
TI  - Changes in hemostatic parameters in hepatic veno-occlusive disease following bone
      marrow transplantation.
AB  - Hepatic veno-occlusive disease (VOD) is a major complication after bone marrow
      transplantation (BMT). Its prediction, diagnosis and treatment remain unclear.
      Examination was made of changes in hemostatic parameters in patients with or
      without VOD after BMT. Twenty-seven children were studied following BMT. Eight of
      them developed VOD. Tissue plasminogen activator (t-PA), plasminogen activator
      inhibitor 1 (PAI-1), thrombomodulin (TM), von Willebrand factor (vWF), factor
      VII, fibrinogen (FBG), FDP, D-dimer (D-D), plasminogen (PLG), thrombin
      antithrombin III (TAT), alpha 2-plasmin inhibitor/plasmin complex (PIC),
      antithrombin III (AT-III), protein C, N-terminal propeptide for type III
      procollagen (P-III-P), were measured weekly from pre-BMT to day 28 after BMT. In
      VOD patients, t-PA and PAI-1 significantly increased (P < 0.05) and FBG
      significantly fell during the post-transplant period (P < 0.05). Significantly
      low AT-III and PLG were also noted before VOD (P < 0.05). There were no changes
      in other hemostatic parameters. t-PA, PAI-1 and FBG would thus appear useful
      markers for the diagnosis of VOD, and AT-III and PLG, predictive markers for VOD.
      The coagulation-fibrinolysis system following endothelial cell damage may
      contribute to the onset of VOD.

PMID- 9156267
TI  - Gastro-intestinal toxicity related to bone marrow transplantation: disruption of
      the intestinal barrier precedes clinical findings.
AB  - The intensive cytotoxic treatment given in connection with bone marrow
      transplantations induces severe injury to the gut consistent with an increase in
      intestinal permeability. Currently, extent of the gut injury is assessed by
      inspecting the mouth and recording symptoms deriving from the gastro-intestinal
      tract. The aims of this study were to evaluate whether changes in permeability
      correlate with clinical assessment of gut toxicity, according to the WHO
      criteria, and also to examine the duration of intestinal permeability after high
      dose chemotherapy. In 18 consecutive patients undergoing bone marrow
      transplantation, gastrointestinal permeability was assessed by a 51Cr-EDTA
      absorption test before the start of cytotoxic treatment, and 4, 7, 10 and 14 days
      after stem-cell infusion. In another seven patients, permeability was assessed 2
      days after the start of cytotoxic treatment, and 1, 7 and 14 days after stem cell
      infusion. During the same period, oral- and non-oral clinical toxicity according
      to the WHO criteria were recorded. Permeability increased significantly 2 days
      after the start of cytotoxic treatment (P < 0.05), on day 1 (P < 0.05), on day 4
      (P < 0.0005), on day 7 (P < 0.0005) and on day 10 (P < 0.005) after stem cell
      infusion, compared with pre-treatment permeability. Despite significant barrier
      dysfunction, clinical toxicity was very moderate in the early transplantation
      course. Gastro-intestinal, but not oral clinical toxicity requiring therapy, was
      consistent with a significant increase in permeability compared with no clinical
      toxicity or toxicity not requiring therapy. Similarly, cumulative gastro
      intestinal, but not oral toxicity correlated positively with the increase in
      permeability. The permeability test was unable to predict the severity of the
      clinical gastro-intestinal toxicity.

PMID- 9156268
TI  - Donor lymphocyte infusions (DLI) in patients with chronic myeloid leukemia
      following allogeneic bone marrow transplantation.
AB  - Donor lymphocyte infusions (DLI) were given between June 1990 and March 1996 to
      18 patients with chronic myeloid leukemia (CML) for the treatment of cytogenetic
      (n = 6) or hematologic relapse (n = 12) following an allogeneic bone marrow
      transplant (BMT). Patients were divided in two groups: patients in group A (n =
      8) received a large dose of donor lymphocytes (> or = 1 x 10(8)/kg), whereas
      patients in group B (n = 10) received escalating numbers of cells (2 x 10(5) up
      to 2 x 10(8)/kg). The median number of DLI in group A was 2 (range 1-3); the
      median number of infusions in group B was 7 (range 3-9). Acute GVHD occurred in
      12 patients (grades I-III) and was a major cause of death in two. The risk of
      developing GVHD correlated with the number of cells infused: 37%, 14%, 5% and 0%
      for DLI with cells > or = 1 x 10(8), 2 x 10(7)/kg, 2 x 10(6)/kg, and 2 x
      10(5)/kg, respectively (P = 0.01). Median transaminase levels were found to be
      significantly increased in patients with, as compared to patients without, acute
      GVHD (GPT 412 vs 28 IU/l; P = 0.03). Severe aplasia occurred in four and was a
      contributing cause of death in two patients. Overall, four patients died as a
      consequence of DLI and all received > 1 x 10(8)/kg cells: the actuarial risk was
      38% in group A and 14% in group B (P = 0.1). There were 10 complete and three
      partial cytogenetic responses: the actuarial probability at 5 years of being Ph
      negative was 69%: it was 46% for group A and 85% for group B (P = 0.1). The
      longest patient is now 6 years post-DLI, Ph negative, BCR-ABL negative. The
      actuarial 3 year survival is 38% in group A and 86% in group B (P = 0.06). The
      study confirms that DLI post-BMT is not innocuous and that there is a definite
      long-lasting antileukemic effect in patients with CML. It also suggests that: (1)
      the risk of developing GVHD correlates with the number of infused cells; (2) that
      significant elevations of serum GPT levels are associated with GVHD; and (3) that
      the use of escalating doses of cells may allow the identification of side-effects
      and discontinuation of infusions before life-threatening GVHD has developed.

PMID- 9156269
TI  - A randomized comparison between early and late vaccination with tetanus toxoid
      vaccine after allogeneic BMT.
AB  - Forty-five adult HLA-matched sibling BMT recipients were randomized to receive
      tetanus toxoid (TT) vaccine at 6, 8 and 14 months (early group, n = 23) or at 18,
      20 and 26 months after BMT (late group, n = 22). At 6 months after BMT, prior to
      the first vaccination, 90% of the early group patients had a protective tetanus
      antibody concentration of > or = 0.1 HU/ml (passive haemagglutination test) but
      only 70% of the late group patients did so at 18 months after BMT. The antibody
      responses 1 month after each of the three TT vaccine doses were similar in the
      two vaccination groups, except that after the first dose, four-fold responses
      occurred more frequently in the late group. All vaccinated patients achieved the
      protective antibody concentration of > or = 0.1 HU/ml. In the late group the
      recipient antibody responses after the first and second vaccine doses correlated
      with the donor anti-TT level. A tetanus vaccination schedule consisting of three
      vaccine doses is equally immunogenic when started at 6 or 18 months after BMT.
      Donor immunity against tetanus may influence recipient responses to TT
      vaccination.

PMID- 9156270
TI  - Myasthenia gravis in association with allogeneic bone marrow transplantation:
      clinical observations, therapeutic implications and review of literature.
AB  - Myasthenia gravis (MG) is a rare complication of allogeneic bone marrow
      transplantation (BMT). We present the 11th case in the medical literature, a 23
      year-old female 100 months post-allogeneic bone marrow transplantation for acute
      myelogenous leukemia (AML). After discontinuation of immunosuppression for
      chronic graft-versus-host disease (GVHD) involving skin, gastrointestinal tract
      and lacrimal glands, the patient developed severe, progressive dysphagia
      initially attributed to esophageal candidiasis. With the development of muscle
      weakness, ptosis, and dysphonia the diagnosis of generalized myasthenia gravis
      was suspected, and confirmed by elevated anti-acetylcholine receptor antibody
      titer and a positive edrophonium challenge. Prednisone and pyridostigmine
      produced improvement, and thymectomy was performed without pathologic evidence of
      thymoma. Recurrent post-operative respiratory distress required transient
      mechanical ventilation. Twenty-seven months after diagnosis, the patient requires
      maintenance prednisone to control symptoms of myasthenia gravis. The clinical
      features of all reported cases of MG post-allogeneic BMT are reviewed, and
      universal features include an association with decreasing immunosuppression, the
      presence of other manifestations of chronic GVHD, anti-acetylcholine receptor
      antibodies, and the absence of an associated thymoma. HLA Cw1, Cw7 and DR2 were
      identified at frequencies significantly above that expected from HLA antigen
      prevalance studies, and may be markers for increased risk of developing MG post
      allogeneic BMT. No statistically significant associations with HLA A2, B7, B35 or
      donor-recipient sex mismatch were present. Reinstitution of immunosuppression and
      standard therapies for myasthenia gravis were effective in the majority of cases.
      The role of thymectomy in this population remains unclear.

PMID- 9156271
TI  - Allogeneic peripheral blood stem cell transplant for myelodysplasia after
      chemotherapy for post-transplant lymphoma in a cardiac transplant recipient at 10
      years.
AB  - A 32-year-old male received an allogeneic peripheral blood stem cell transplant
      (alloPBSCT) for myelodysplasia from his one HLA-A antigen mismatched brother. He
      is alive with trilineage engraftment and without active GVHD 200 days after
      transplant. In July 1986 he underwent orthotopic cardiac transplantation for
      viral cardiomyopathy and has received continuous immunosuppressive therapy. A
      post-transplant lymphoproliferative disorder with Hodgkin-like histopathology was
      diagnosed in August 1993 and was successfully treated with four cycles of MOPP
      chemotherapy. Due to persistent pancytopenia he underwent a bone marrow
      aspiration and biopsy in May 1996 which revealed monosomy 7 and morphologic
      changes compatible with myelodysplasia. This is the first report of a cardiac
      transplant recipient receiving an allogeneic hematopoietic stem cell transplant.

PMID- 9156272
TI  - Polychemotherapy combined with G-CSF-mobilized donor buffy coat transfusion for
      granulocytic sarcoma after allogeneic BMT for AML.
AB  - In 1988, a 27-year-old male patient received an allogeneic BMT for leukemic
      relapse 8 months after ABMT for AML (M2) in first complete remission. Because of
      chronic GVHD of the liver CsA was administered until 1994. Nine months after
      discontinuation of CsA, locally advanced gastric granulocytic sarcoma (GS) was
      diagnosed without evidence of systemic relapse. The patient was treated with two
      courses of polychemotherapy (ICE, NOVIA). Granulocyte colony-stimulating factor
      (G-CSF)-mobilized donor buffy coat cells were reinfused after each chemotherapy
      cycle in an attempt to accelerate hematopoietic regeneration and to induce a
      graft-versus-leukemia (GVL) effect. Local irradiation and surgical resection of
      residual leukemic cells resulted in complete remission. Seventeen months from
      diagnosis of GS the patient relapsed again with multiple lesions and died of
      generalized bleeding during aplasia after a third course of polychemotherapy
      (ICE). In our patient donor peripheral blood stem cell support did not accelerate
      hematopoietic regeneration (time to neutrophil recovery > 0.5 x 10(9) g/l from
      the start of chemotherapy was 27 days after ICE and 36 days after NOVIA) and did
      not result in long-term disease-free survival.

PMID- 9156273
TI  - Anti-mitosin antibodies in a patient with chronic graft-versus-host disease after
      allogeneic bone marrow transplantation.
AB  - In a patient undergoing allogeneic BMT for ALL, chronic GVHD (cGVHD) with skin
      changes developed within 110 days after transplantation. One year post-BMT, anti
      nuclear antibodies were detected. The patient's serum was used for
      immunoscreening of a HeLa cDNA library. Ten different overlapping positive clones
      were found to be partial clones of mitosin, a 350-kDa nuclear phosphoprotein
      which shows a speckled nuclear distribution in S phase and which relocates to the
      centromere and mitotic apparatus in M phase. Although autoantibodies against
      centromere protein-F, which is very similar to mitosin, have been reported in
      patients with cancer, this is the first report of autoantibodies against mitosin
      in a patient with cGVHD.

PMID- 9156274
TI  - Trichostrongylus infestation masquerading as conditioning toxicity of the gut in
      bone marrow transplantation.

PMID- 9156275
TI  - Listeriosis in bone marrow transplant recipients.

PMID- 9156276
TI  - Chagas' disease after bone marrow transplantation.

PMID- 9156277
TI  - The molecular pathology of neoplasia.

PMID- 9156278
TI  - Molecular pathology of breast cancer and its application to clinical management.
AB  - Breast cancer is a major cause of morbidity and mortality in women in many parts
      of the world. Breast carcinomas are heterogenous in their biological and clinical
      behaviour and a greater understanding of how they develop and progress could lead
      to more directed forms of screening and therapy. It is important to determine the
      molecular mechanisms underlying the natural history of breast cancer.
      Developments in the techniques for molecular analysis have meant that they can
      now be applied to a large range of clinical material such as cytological
      preparations and fixed, embedded material, so increasing the potential for
      relating any molecular alterations to clinical behaviour and response to therapy.
      In this review we consider recent developments in three areas of importance to
      breast cancer; genetic analysis-oncogenes, tumour suppressor genes, loss of
      heterozygosity, microsatellite instability, familial breast cancer; steroid
      receptors, oestrogen regulated proteins, epidermal growth factor receptor, growth
      factors particularly transforming growth factor beta; and cell adhesion, invasion
      and metastasis-E-cadherin, integrins, proteases. These are discussed in relation
      to potential for screening, prognosis and treatment.

PMID- 9156279
TI  - Molecular and cellular biology of prostate cancer.
AB  - Prostate cancer is an enigmatic disease. Although prostatic-intraepithelial
      neoplasia appears as early as the third decade and as many as 80% of 80 year old
      men have epithelial cells in their prostate that fit the morphological criteria
      for cancer, only about 10% of men will ever have the clinical disease and less
      than 3% will die from it. There have been no significant proven interventions
      which have altered the natural history of the disease since hormone down
      regulation was introduced in the 1940s and new research has been poorly
      supported. There is however an urgent need to develop new criteria to distinguish
      those patients with localised disease who will benefit from intervention from
      those that do not require it or who will have occult extra prostatic metastases.
      Similarly, there is an urgent need to develop new treatments for those in whom
      the disease is extra-prostatic and therefore incurable by conventional
      treatments. This review covers the latest developments in epidemiology, cellular
      and molecular biology including new areas such as ion channels in the field of
      prostate cancer.

PMID- 9156280
TI  - Molecular genetics of colon cancer.
AB  - Colorectal cancer remains a major health problem. Few therapies are effective
      apart from surgery, and survival has increased little in recent years. This is
      despite the fact that screening by colonoscopy can potentially remove nearly all
      colorectal tumours before they become malignant. Molecular genetics has
      identified some inherited mutations (such as at APC and the mismatch repair loci)
      that predispose to colon cancer and some somatic mutations (such as at APC and
      p53) that cause sporadic colon tumours. We review the likely role of these and
      other genes in colorectal tumorigenesis. We also highlight areas of relative
      ignorance in colon cancer and emphasise that many important genes, especially
      those that cause invasion and metastasis, remain to be identified. Colorectal
      cancer is, however, a well characterised tumour, as regards both its natural
      history and its histopathology; there are consequently good prospects for
      advances in colon cancer genetics, with probable benefits for its treatment. We
      anticipate: (a) that new genes predisposing to colon tumours, including those
      conferring relatively minor risks, will be characterised; (b) genes and proteins
      important in invasion and metastasis will be identified; (c) the network of
      protein interactions in which molecules such as APC are involved will be
      elucidated; (d) large-scale studies of somatic mutations in tumours will provide
      accurate predictions of prognosis and suggest optimal therapeutic regimens; and
      (e) new potential targets for therapy will be identified. Whilst molecular
      genetics is by no means sufficient for progress in preventing and treating colon
      cancer, it is a necessary and central part of such advances.

PMID- 9156281
TI  - Molecular approaches to diagnosis and management of ovarian cancer.
AB  - The recent advances in the understanding of the pathogenesis of ovarian cancer
      have been helpful in addressing issues in diagnosis, prognosis and management.
      The study of ovarian tumours by novel techniques such as immunohistochemistry,
      fluorescent in situ hybridisation, comparative genomic hybridisation, polymerase
      chain reaction and new tumour markers have aided the evaluation and application
      of new concepts into clinical practice. The correlation of novel surrogate tumour
      specific features with response to treatment and outcome in patients has defined
      prognostic factors which may allow the future design of tailored therapy based on
      a molecular profile of the tumour. These have also been used to design new
      approaches to therapy such as antibody targeting and gene therapy. The
      delineation of roles of c-erbB2, c-fms and other novel receptor kinases in the
      pathogenesis of ovarian cancer has led initially to the development of anti-c
      erbB2 monoclonal antibody therapy. The discovery of BRCA1 and BRCA2 genes will
      have an impact in the diagnosis and the prevention of familial ovarian cancer.
      The important role played by recessive genes such as p53 in cancer has raised the
      possibility of restoration of gene function by gene therapy. Although the
      pathological diagnosis of ovarian cancer is still confirmed principally on
      morphological features, addition of newer investigations will increasingly be
      useful in addressing difficult diagnostic problems. The increasingly rapid pace
      of discovery of genes important in disease, makes it imperative that the
      evaluation of their contribution in the pathogenesis of ovarian cancer is
      undertaken swiftly, thus improving the overall management of patients and their
      outcome.

PMID- 9156282
TI  - Molecular diagnosis of lymphomas and associated diseases.
AB  - The aim of this review is to explore some of the major ways in which the
      techniques of molecular biology are affecting individual patient diagnosis with
      respect to lymphoproliferative disorders. The main impact in this particular
      sphere has been through the polymerase chain reaction which has enabled clonal
      analysis, the detection of diagnostically and prognostically important
      chromosomal abnormalities and the monitoring of therapeutic intervention via the
      detection of residual disease. This allows increased diagnostic accuracy and
      enables better targeting of therapeutic intervention. A younger technology, but
      none the less one with great diagnostic potential, is that of fluorescence in
      situ hybridisation which has bridged the gap between conventional cytogenetics,
      with its reliance on living tissues and its relative insensitivity in picking up
      chromosomal abnormalities, and molecular biology which forsakes morphology and
      which, in the shape of PCR at least, deals with relatively minute segments of the
      genome. The main techniques of clonal analysis are compared and contrasted and
      the usefulness of the detection of some of the major chromosomal abnormalities is
      discussed. The place of fluorescence in situ hybridisation is also elaborated.
      The major advantages and disadvantages of each of these techniques are described
      and their place in the scheme of diagnosis and treatment is briefly elucidated.

PMID- 9156284
TI  - Molecular pathology of melanoma.
AB  - There has long been a clinical need for improved molecular pathology in melanoma,
      particularly in the histopathology laboratory where the differentiation of
      melanoma from its benign counterparts is commonly difficult. The need for
      improved molecular pathology has recently increased as immunotherapeutic options
      for the treatment of the tumour evolve. It seems likely that in the relatively
      near future tumour typing before and during immunotherapy will be needed. The
      identification of the tumour suppressor gene coding for the protein p16 as an
      important gene in the pathogenesis of melanoma is of great interest but the
      identification of oncogenes having a significant role in melanoma carcinogenesis
      has been slow.

PMID- 9156283
TI  - Genetics of renal tumours.
AB  - The two main renal tumours, Wilms' tumour and renal cell carcinoma, are
      associated with distinct molecular genetic abnormalities. The genes involved
      behave as Knudson oncosuppressor genes. Further dissection of the molecular
      biology pathways involving WT1 and VHL genes is providing fascinating insight
      into the biology of these genes, the development and cell biology of the kidney
      and its tumours.

PMID- 9156285
TI  - Molecular and cellular pathology of intrinsic brain tumours.

PMID- 9156286
TI  - Molecular approaches to neuroendocrine pathology.
AB  - Prognosis of many tumour types is influenced by the degree of neuroendocrine
      differentiation. Neuroendocrine tumours produce bioactive peptides and amines
      that can have major disruptive effects on physiology. In the past, investigation
      of neuroendocrine pathology has relied upon traditional histological staining
      methods and morphological analysis at light and electron microscopic level. While
      these methods are still invaluable, the use of immunocytochemical techniques has
      revolutionised the diagnosis and understanding of neuroendocrine tumours,
      allowing precise identification of tumour types by means of antibodies to general
      neuroendocrine markers and tumour-specific antigens. However, the
      histogenesis/oncogenesis of neuroendocrine neoplasia cannot be understood by
      characterising the tumour products alone. Molecular technology has made possible
      investigation of gene expression by in situ hybridisation, electrophoresis and
      Northern or Southern blotting, and highly specific and sensitive techniques such
      as the polymerase chain reaction. Where gene expression and gene product storage
      are poorly correlated, molecular pathology provides vital information to aid
      diagnosis. Understanding of genetic factors involved in the familial
      neuroendocrine syndromes such as multiple neuroendocrine neoplasia (MEN) has
      improved. Oncogenes, tumour-suppressor genes and transcription factors have been
      identified. The factors controlling cell proliferation, growth and progression of
      tumours can be investigated at molecular level. Expression of amidating enzymes
      along with bioactive products including growth factors raises the question of
      whether tumour growth can be controlled or prevented by inhibition of amidating
      enzymes that activate the growth factors.

PMID- 9156287
TI  - The clinical role of molecular genetics in soft tissue tumor pathology.
AB  - Cytogenetic and molecular analysis of soft tissue tumors has yielded a wealth of
      information over the past decade. Some of the genetic aberrations that have been
      identified appear to be fairly specific for individual tumor types. It is because
      of this specificity that these findings harbor the promise to become useful as
      diagnostic and/or prognostic markers. Technical advances that allow the
      application of cytogenetic and molecular techniques to archival material have
      been crucial in this respect. Molecular genetics has already become an integral
      part of the work-up of some tumors, e.g., small cell sarcomas of childhood, which
      demonstrate fairly characteristic translocations, often involving the Ewing's
      sarcoma gene. Some genetic abnormalities have become established as prognostic
      markers, such as the deletion of the short arm of chromosome 1 for
      neuroblastomas. Soft tissue tumor pathology has also benefitted from major
      advances in identifying genes that are critical in mesenchymal differentiation or
      cell cycle control. MyoD is a good example of a such a gene, that has become
      useful as a diagnostic tool in rhabdomyosarcomas. Beyond potential practical
      applications of cytogenetic and molecular analyses in the diagnosis of these
      tumors, we also review their impact on several philosophical concepts concerning
      soft tissue neoplasia.

PMID- 9156288
TI  - Pathophysiology of chest trauma.
AB  - Recent information indicates that there is a complex cellular and molecular
      generic response to injury that can lead to multi-organ failure. For many years,
      basic physiology and biochemistry were considered to be the systemic mechanisms
      to injury, but now it is known that subcellular and molecular events are the keys
      to unlocking the secrets of the body's response to trauma. The interaction of the
      endothelial cell with neutrophils and platelets to produce cytokines, free
      radicals, and upregulating adhesion molecules is especially significant.

PMID- 9156289
TI  - Newer diagnostic measures and emergency management.
AB  - Evolving technology provides new diagnostic and emergency management options for
      the surgeon caring for patients with thoracic trauma. Abdominal ultrasound
      performed by surgeons in the emergency department makes pericardiocentesis and
      subxyphoid pericardiotomy obsolete. Transesophageal echocardiography supplements
      aortography in the diagnosis of thoracic aortic injury. New terminologies replace
      the overused term myocardial contusion. Pulmonary tractotomy is an innovative
      approach to through-and-through pulmonary penetrating injuries. Centrifugal pumps
      add new options to thoracic great-vessel injury management. Endovascular stented
      grafts will be added to the armentarium of the thoracic surgeon for injured
      vessels.

PMID- 9156290
TI  - Anesthetic considerations in chest trauma.
AB  - At the R. Adams Cowley Shock Trauma Center, participation of anesthesiologists in
      the care of thoracic trauma victims begins with the initial assessment of
      patients on arrival by helicopter or ambulance. It continues with management of
      the airway, stabilization of hemodynamics, intraoperative management, patient
      care in the PACU and critical care setting, and acute pain management. By using a
      team approach involving anesthesia, surgery, and critical care, the care of
      trauma victims with thoracic injury continues to be enhanced.

PMID- 9156291
TI  - The fractured rib in chest wall trauma.
AB  - Chest wall trauma and rib fractures are significant sources of morbidity and
      mortality in countries in which motor vehicle accidents are prevalent. Physicians
      who care for injured patients should realize that patients with thoracic trauma
      are at significant risk for mortality, deterioration, and associated injuries.
      Care must be taken to avoid underestimation of the effect of the injury on
      subsequent respiratory mechanics. Armed with an understanding of chest injury
      epidemiology, biomechanics, and pain control, physicians can better serve these
      high-risk patients.

PMID- 9156292
TI  - Trauma to the lung.
AB  - Injuries to the lung parenchyma occur following both blunt and penetrating trauma
      and usually are associated with injury to adjacent structures. In most cases,
      patients with lung injury require little more than chest-tube insertion and
      supportive care. A thoracotomy is required, however, in approximately 10% of
      these patients, half of whom will need pulmonary repair or resection. Because
      serious morbidity and mortality can follow lung injuries, surgeons must have a
      broad understanding of the causes, types, and pathophysiologies of lung injuries
      and be able to promptly diagnose and appropriately treat them.

PMID- 9156293
TI  - Traumatic injury of the cervicothoracic trachea and major bronchi.
AB  - Interstate highways and crowded urban areas have become the "battlefields" of the
      1990s. The weapons are motor vehicles, handguns, and knives. This article relates
      the historical perspective, diagnosis, and management of traumatic injury to the
      cervicothoracic trachea and major bronchi. The etiologic factors are explained in
      depth. Examples of the current management of cervicothoracic tracheal injuries,
      including resection, primary repair, and the use of autogenous tissue to buttress
      or wrap the repair, are explained and illustrated.

PMID- 9156294
TI  - Trauma to the aorta and major vessels.
AB  - Techniques for the diagnosis of blunt thoracic vascular injuries continue to
      evolve, and both helical CT scanning and transesophageal echocardiography are
      being compared with thoracic aortography. Repair of a tear in the descending
      thoracic aorta often is performed with the antriofemoral centrifugal pump.
      Patients with penetrating thoracic vascular injuries have a variety of
      presentations, with aortography restricted to those with proximity of wound to
      the superior mediastinum or the presence of a hematoma on admission chest
      radiograph.

PMID- 9156295
TI  - Trauma to the heart.
AB  - Traumatic injury to the heart is no longer a death sentence. Efficient urban
      transport systems and surgeons who are expert in trauma care combine to achieve
      meaningful survival rates after both penetrating and blunt violations of the
      heart. Almost all cases of injury to the heart can be repaired without
      cardiopulmonary bypass and, therefore, are within the purview of the thoracic
      surgical trauma specialist.

PMID- 9156296
TI  - Missiles in the cardiovascular system.
AB  - A missile in the cardiovascular system is a rare complication of a projectile
      wound. A missile in the heart should be suspected in the patient with a
      projectile wound of the thorax and in whom, on chest radiography, a missile is
      seen in the cardiac silhouette. A missile should be suspected in the patient with
      a projectile wound elsewhere with similar radiographic findings, no exit wound,
      and no missile in the area of injury. A missile in the arterial system should be
      suspected when no exit wound and no projectile are seen in the traumatized area.
      In such a case, radiography of the entire body should be done. The diagnosis of a
      suspected missile in the cardiovascular system is confirmed by echocardiography
      or angiography. Treatment should be individualized according to the clinical
      manifestations of the patient and the site of the missile.

PMID- 9156297
TI  - Esophageal injuries.
AB  - Esophageal injuries may accompany any type of trauma. A high index of suspicion
      that esophageal injury has occurred is the most important first step in
      diagnosing and treating these injuries. Various diagnostic modalities are
      available to evaluate esophageal injuries, and all should be used judiciously in
      diagnosing the position and extent of the injury. Therapy depends on the extent
      of the injury, its anatomic location in the esophagus, and the elapsed time
      between the injury and repair.

PMID- 9156298
TI  - Trauma to the diaphragm.
AB  - Traumatic diaphragmatic hernia is being seen with increasing frequency. Early
      recognition is of upmost importance because catastrophic complications may occur
      at any time following the diaphragmatic disruption. A high index of suspicion,
      history of previous thoracoabdominal trauma, physical examination of the chest,
      and roentgenographic evidence should aid in early and definitive diagnosis. All
      patients with serious body injury should have upper and lower gastrointestinal
      series performed before hospital discharge. Right-sided herniation occurs with
      more frequency than previously reported. In managing these injuries, the
      transabdominal route should be used in acute ruptures; chronic herniation should
      be approached through the chest, with the addition of a separate laparotomy when
      indicated.

PMID- 9156299
TI  - Traumatic thoracic fistulas.
AB  - This article considers the wide range of fistulas that can result from blunt and
      penetrating trauma. The mechanisms, physical signs, diagnostic techniques, and
      nonoperative and operative management strategies for fistulas of the thorax are
      reviewed. Emphasis is placed on the requirement for a high index of suspicion in
      specific types of injury in which thoracic fistulas can occur.

PMID- 9156300
TI  - Thoracic infection after trauma.
AB  - Thoracic infections following injury are common, with pneumonia and empyema being
      the most prevalent. Pneumonia may follow all types of injury, and empyema occurs
      most frequently after chest injuries. Mediastinitis, lung abscess, and
      pericarditis occur rarely in the trauma patient. An organized approach to
      diagnosis and treatment is essential in the management of these problems.

PMID- 9156301
TI  - Traumatic adult respiratory distress syndrome.
AB  - ARDS is the pulmonary manifestation of both direct and indirect insults to the
      lung. Trauma patients are at particular risk for ARDS from the direct effects of
      their injuries, as well as from complications that may occur during their
      hospital courses. ARDS prevention can be enhanced through diverse areas of
      medical focus. Public health issues addressing trauma prevention, improved
      understanding and treatment of trauma-related pathophysiology, as well as a
      better understanding of basic pathophysiology of this disease process will allow
      refinement and improvement of our management practices. Newer modes of mechanical
      ventilation may help us to avoid ventilator-induced exacerbation of lung injury.
      As we define the role of nonconventional therapies, such as anti-inflammatory and
      anticytokine therapies, our ability to actively interrupt and reverse the
      progression of the inflammatory cascade will be enhanced. As yet, ARDS continues
      to be a challenging disease process to both fully understand and successfully
      treat in our critically ill patients.

PMID- 9156302
TI  - Unsuspected and unrelated pathology noted on limited computed tomographic scans
      of the paranasal sinuses and temporal bone.
AB  - Modern imaging includes many studies performed to examine limited fields of view
      (i.e., paranasal sinus studies). These studies are frequently retrospectively
      coned to the limited field of view and are often examined only at one window and
      level setting. However, classic radiology teaching demands that all irradiated
      structures be examined by a qualified physician; for examples, on an intravenous
      pyelogram the examiner should look at not only the kidneys, ureters, and bladder,
      but also the bones, soft tissues, and gas patterns. This article illustrates
      unsuspected intracranial pathology noted on computed tomographic examinations of
      the paranasal sinuses and temporal bones.

PMID- 9156303
TI  - Color and pulsed Doppler evaluation of benign and malignant adenopathy.
AB  - A color and pulsed Doppler evaluation of 140 benign and malignant lymphnodes in
      85 patients has been performed: The nodes have been classified into non
      vascularized (flow-), normal-vascularized (flow +), and hypervascularized (flow
      +2); we also considered the presence of central or peripheral flow. Resistivity
      index was also measured. The only parameters showing statistical significance
      were flow - and flow +. The authors conclude that there is a higher probability
      of benignancy than malignancy in an avascular node, while the opposite is true in
      a node with moderate flow.

PMID- 9156304
TI  - MR imaging of dedifferentiated chondrosarcoma.
AB  - MR imaging of a dedifferentiated chondrosarcoma of the humerus is presented and
      correlated with gross and microscopic histology from the surgical specimen. The
      classification of chondrosarcoma and specific MR signal characteristics that
      suggest dedifferentiation are discussed.

PMID- 9156305
TI  - Clinical utility of computed tomography in the diagnosis of pulmonary embolism.
AB  - This prospective clinical pilot study describes the clinical utility and cost
      effectiveness of computed tomography (CT) with contrast in the diagnosis and
      management of pulmonary embolism. The setting is a university teaching hospital,
      and the 20 patients, 26 to 81 years old, were found to have CT findings
      consistent with pulmonary embolism. Intraluminal pulmonary artery clots were
      observed on CT and contributed to clinical management, often obviating pulmonary
      arteriography. CT, particularly spiral CT, may demonstrate pulmonary embolism and
      offers advantages over ventilation-perfusion lung scanning and pulmonary
      arteriography in making the diagnosis of pulmonary embolism in high-risk patients
      or patients with preexisting parenchymal lung disease.

PMID- 9156306
TI  - CT of pancreatitis with renal and juxtarenal manifestations.
AB  - Involvement of the juxtarenal spaces and kidneys in pancreatitis has been well
      known. Although delineation of the regions of accumulation of exudate has been
      elegantly confirmed with the advent and advance of refined computerized
      tomography (CT) there has been relatively little description in the earlier
      literature of these phenomena. This essay serves to illustrate the wide range of
      findings that have been encountered and recorded more recently.

PMID- 9156307
TI  - Localized benign pleural mesothelioma arising in a radiation field.
AB  - Localized benign pleural mesothelioma is a rare neoplasm representing less than
      5% of all pleural tumors. Unlike the malignant diffuse pleural mesothelioma,
      there is no evidence of a relationship to asbestos exposure. Essentially, the
      cause of localized benign pleural mesotheliomas remains obscure. We propose that
      one mechanism of the development of this tumor is prior ionizing radiation to the
      tumor field. Ionizing radiation is a well-known human oncogen and leads to an
      increased incidence of benign tumors as well. A 65-year-old woman had a localized
      benign pleural mesothelioma of her left upper chest 22 years following adjuvant
      radiation therapy to the left breast and axillary region for a breast carcinoma.

PMID- 9156308
TI  - Expanding aneurysm of aberrant right subclavian artery. Case report and imaging
      evaluation.
AB  - We present a case illustrating the complementary role of CT and angiography in
      evaluation of a slowly expanding vascular thoracic mass representing aneurysmal
      enlargement in an aberrant right subclavian artery. Anatomy, embryology,
      incidence, and imaging of aberrant right subclavian artery, bicarotid trunk, and
      aneurysmal dilatation of the diverticulum of Kommerell are reviewed.

PMID- 9156309
TI  - Massive renal angiomyolipoma in tuberous sclerosis.
AB  - A massive renal angiomyolipoma, measuring 45 x 20 x 15 cm and weighing 3,500 g in
      a patient with tuberous sclerosis is presented. While renal angiomyolipomas may
      become quite large, this is one of the largest such tumors ever reported.

PMID- 9156310
TI  - Absence of flow in ovarian vein by time-of-flight magnetic resonance angiography
      without evidence of thrombosis.
AB  - A case of absent flow in the left ovarian vein was diagnosed on time-of-flight
      (TOF) magnetic resonance angiography (MRA) while investigating for pelvic vein
      thrombosis in a 53-year-old female. This appearance should not be misdiagnosed as
      a sign of ovarian vein occlusion or thrombosis. Magnetic resonance imaging (MRI)
      is a sensitive noninvasive imaging modality in such a clinical setting.
      Familiarity with the potential pitfalls of different MRA techniques is essential
      for correct diagnosis. A review of different MRA techniques in evaluation of
      pelvic venous thrombosis is presented.

PMID- 9156311
TI  - Nodular liver involvement in light chain multiple myeloma: appearance on US and
      MRI.
AB  - Nodular liver infiltration with multiple myeloma is very rare and its findings on
      MR images have not been, to our knowledge, previously described. The authors
      report a case of light chain multiple myeloma nodular liver involvement and
      describe its appearance on US and MRI. Despite their rarity these lesions have
      distinct MRI features and should be considered in the differential diagnosis of
      multiple lesions with high SI on T1-weighted images.

PMID- 9156312
TI  - Computed tomography of the superior mesenteric artery syndrome.
AB  - An acute presentation of the superior mesenteric artery syndrome was diagnosed in
      a 13-year-old Chinese boy in whom no predisposing cause was found at surgery.
      Duodenogram combined with dynamic computed tomography, including 2-dimensional
      multiplanar reconstructions, was useful in confirming the diagnosis prior to
      definitive surgery.

PMID- 9156313
TI  - Sensorineural hearing loss and cerebellopontine angle lesions. Not always an
      acoustic neuroma--a pictorial essay.
AB  - While an acoustic neuroma is the most common cause of a cerebellopontine angle
      (CPA) mass, it accounts for only 1-10% of cases of sensorineural hearing loss
      (SNHL). There are many other etiologies of SNHL, with characteristic imaging
      features, which may or may not be confined to the CPA.

PMID- 9156314
TI  - Development and clinical application of an innovative fluorescence in situ
      hybridization technique which detects submicroscopic rearrangements involving
      telomeres.
AB  - We report an innovative fluorescence in situ hybridization technique which
      exploits a unique resource of 41 telomere-specific probes and allows the
      simultaneous analysis of the subtelomeric region of every chromosome for
      deletion, triplication and balanced translocation events. This technique requires
      only a single microscope slide per patient and is expected to be a useful
      diagnostic tool with applications in the fields of idiopathic mental retardation,
      the detection of congenital abnormalities and in some forms of cancer. This will
      lead to more accurate genetic counselling of patients and their families and will
      provide the basis for future diagnostic, therapeutic and preventative measures.

PMID- 9156315
TI  - Nephropathic cystinosis (CTNS-LSB): construction of a YAC contig comprising the
      refined critical region on chromosome 17p13.
AB  - A yeast artificial chromosome (YAC) contig was constructed encompassing the
      entire region on chromosome 17p13 where the autosomal recessive disorder
      infantile nephropathic cystinosis (MIM 21980, CTNS-LSB) has been genetically
      mapped. It comprises seven clones ordered by their content of a series of six
      sequence-tagged sites (STSs). Fluorescence in situ hybridisation (FISH) revealed
      two chimaeric clones. The order of four polymorphic STSs mapped with the contig
      was consistent with that of the known genetic map with the exception of markers
      D17S1583 (AFMb307zg5) and D17S1798 (AFMa202xf5) where a telomeric location of
      D17S1583 was inferred from the contig; two non-polymorphic STSs were localised
      within the marker frame-work. From the analysis of recombination events in an
      unaffected individual as defined by leucocyte cystine levels we support the high
      resolution mapping of this region to a small genetic interval and show that it is
      entirely represented on a single, non-chimaeric YAC clone in the contig.

PMID- 9156316
TI  - Characterisation of five missense mutations in the cystathionine beta-synthase
      gene from three patients with B6-nonresponsive homocystinuria.
AB  - Homocystinuria, due to a deficiency of the enzyme cystathionine beta-synthase
      (CBS), is an inborn error of sulphur-amino acid metabolism. This is an autosomal
      recessive disease which results in hyperhomocysteinaemia and a wide range of
      clinical features, including optic lens dislocation, mental retardation, skeletal
      abnormalities and premature thrombotic events. We report the identification of 5
      missense mutations in the protein-coding region of the CBS gene from 3 patients
      with pyridoxine-nonresponsive homocystinuria. Reverse-transcription PCR was used
      to amplify CBS cDNA from each patient and the coding region was analysed by
      direct sequencing. The mutations detected included 3 novel (1058C-->T, 992C-->A
      and 1316G-->A) and 2 previously identified (430G-->A and 833C-->T) base
      alterations in the CBS cDNA. Each of these mutations predicts a single amino acid
      substitution in the CBS polypeptide. Appropriate cassettes of patient CBS cDNA,
      containing each of the above defined mutations, were used to replace the
      corresponding cassettes of normal CBS cDNA sequence within the bacterial
      expression vector pT7-7. These recombinant mutant and normal CBS constructs were
      expressed in Escherichia coli cells and the catalytic activities of the mutant
      proteins were compared with normal. All of the mutant proteins exhibited
      decreased catalytic activity in vitro, which confirmed the association between
      the individual mutation and CBS dysfunction in each patient.

PMID- 9156317
TI  - Erythrocyte glucose-6-phosphate dehydrogenase deficiency in Poland--a study on
      the 563 and 1311 mutations of the G6PD gene.
AB  - Studies on the mutation 563T and silent mutation 1311T of the glucose-6-phosphate
      dehydrogenase (G6PD) gene in Poland were performed in 26 families affected with
      G6PD deficiency classified-according to WHO-as group 2 G6PD deficiency. Both
      mutations were found in 19 families, including 17 of Polish origin. Mutation 563T
      alone was found in 1 Greek female. The frequency of the silent mutation 1311T in
      Polish unaffected controls was 0.10. It is postulated that at least parts of the
      Polish (or Middle-Eastern European) and Mediterranean populations are of a common
      origin.

PMID- 9156318
TI  - Mitochondrial DNA and Y chromosome-specific polymorphisms in the Seminole Tribe
      of Florida.
AB  - Mitochondrial DNA (mtDNA) sequence variation was examined in 37 Seminoles from
      Florida by polymerase chain reaction amplification and high resolution
      restriction endonuclease analysis. The Y chromosome TaqI restriction fragment
      length polymorphisms detected by the probes 49a, 49f, and 12f2 were examined in
      the 26 males of this group. Analysis of the mtDNA revealed that all four Native
      American haplogroups (A, B, C and D) were present in the Seminoles encompassing
      about 95% of the Seminole mtDNAs. No European mtDNAs were found among the
      Seminoles, but two mtDNAs (about 5%) were members of the African-specific
      haplogroup L1, thus indicating that a limited number of African women were
      incorporated in the Seminole tribe. Analysis of Y chromosome haplotypes supports
      the hypothesis that haplotypes 18 and 63 are the most likely founding Native
      American Y chromosome haplotypes from Asia. However, 11% of the Seminole Y
      chromosomes represented haplotypes generally attributed to Europeans, though none
      harbored standard African haplotypes. These findings support historical evidence
      that the Seminole tribe has integrated individuals of European and African
      ancestry, but suggests that the sex ratio of nonnatives from different continents
      may have varied.

PMID- 9156319
TI  - Uniparental disomy in cartilage-hair hypoplasia.
AB  - Cartilage-hair hypoplasia (CHH) is an autosomal recessive disorder that presents
      with pleiotropic manifestations including impaired skeletal growth and cellular
      immunity. It is most prevalent among two founder populations, the Old Order Amish
      in the USA and the Finns. The gene has been localized to 9p13 by linkage analysis
      and linkage disequilibrium mapping. A statistically significant deficiency of
      affected members resulting in a lower than expected segregation ratio has been
      reported in the Amish, but was not found in a previous study in Finnish CHH
      families. Reduced penetrance was the mechanism suggested in the Amish, but could
      not be verified by haplotype analyses performed after the assignment of the CHH
      gene. Here we have carried out segregation analysis of 101 Finnish CHH families,
      but again, evidence of a significant deficiency of affected members was not
      found. Nevertheless, among 54 uniplex families, 2 patients with CHH and
      uniparental disomy (UPD) for chromosome 9 were discovered. UPD might contribute
      to low segregation ratios by increasing the number of families with only 1
      affected individual. These observations show that UPD may occur in an
      unexpectedly high number of the patients and should be taken into account in the
      genetic counselling and prenatal diagnostics of CHH families.

PMID- 9156320
TI  - Association of extracolonic manifestations of familial adenomatous polyposis with
      acetylation phenotype in a large FAP kindred.
AB  - Familial adenomatous polyposis coli (FAP) has been shown to be associated with
      germline mutations of the adenomatous polyposis gene (APC) on chromosome 5. Extra
      colonic manifestations also occur in FAP and include desmoid tumors, epidermoid
      cysts and osteomas. The combination of FAP with extracolonic symptoms is commonly
      referred to as Gardner's syndrome. It remains difficult, however, to predict
      which patients may have a propensity to develop extracolonic manifestations. The
      rapid acetylation phenotype is believed to be associated with an increased
      likelihood of sporadic colorectal cancer, whereas the slow acetylation phenotype
      is recognized as a predisposing factor for bladder cancer. The slow acetylation
      phenotype is caused by mutant alleles of the cytosolic enzyme N-acetyltransferase
      (NAT2). In this study, we determined the NAT2 genotype in members of one large
      FAP family and three smaller ones all of which had been shown to harbor the same
      germline APC gene mutation. We observed a significant correlation between slow
      acetylation genotypes and extracolonic manifestations of the disease. Rapid
      acetylation genotypes were not overrepresented in colorectal cancer cases in this
      family as compared to the frequency of this genotype in the normal Caucasian
      population.

PMID- 9156321
TI  - Altered mRNA expression due to insertion or substitution of thymine at position
      +3 of two splice-donor sites in the androgen receptor gene.
AB  - We have discovered two types of 5' intronic gene mutation that impair androgen
      receptor (AR) mRNA expression severely, and cause complete androgen
      insensitivity. Labium majus skin fibroblasts (LMSF) hemizygous for each mutation
      had negligible specific androgen binding, and did not react to an antibody
      against an N-terminal peptide of the AR. Both mutations were detected by direct
      sequencing of exons PCR-amplified with flanking primers. One mutation is an
      adenine to thymine transversion at position +3 of the intron 6 splice-donor site.
      Using LMSF mRNA, RT-PCR of a portion of the AR androgen-binding domain yielded a
      small amount of a 302-bp mutant fragment instead of a 433-bp wild-type product.
      Sequencing established that exon 5 was followed, out of frame, by exon 7: exon 6
      was skipped. The other mutation is a thymine insertion at the +3 position of the
      intron 1 donor-splice site. RT-PCR and sequencing revealed a small amount of
      normal-size mRNA with normal exon 1-exon 2 splicing. Quantitative RT-PCR on
      mutant LMSF showed AR mRNA levels were well below 10% of normal; hence, most of
      the aberrant AR mRNA resulting from each mutation is probably unstable. The
      misbehavior caused by these two mutations indicates that in the AR the splice
      donor site +3 adenine is critical; indeed, 57% of eukaryotic introns have adenine
      in the +3 position, while only 2% have thymine.

PMID- 9156322
TI  - Population studies of human deoxyribonuclease I polymorphism.
AB  - We have improved the resolution of the conventional method for phenotyping
      deoxyribonuclease I (DNase I), which makes use of isoelectric focusing, by the
      addition of amphoteric separators. The distribution of DNase I phenotypes was
      extensively examined using this improved method in 1,212 unrelated individuals
      from a Japanese population. In order to investigate a possible difference in
      phenotype distribution between different populations, DNA samples from Germans
      and African Americans were genotyped using the polymerase chain reaction. The
      DNASE1*2 allele in the German population was found to be predominant among the
      four alleles of DNase I, in contrast to the Japanese population. These results
      are the first to demonstrate a wide distribution of DNase I polymorphism in the
      Japanese population as well as in two other populations.

PMID- 9156323
TI  - Nucleotide sequence, chromosome localization, and evolutionary conservation of a
      serine hydroxymethyltransferase-processed pseudogene.
AB  - The nucleotide sequence and chromosomal localization of a human pseudogene is
      reported. Sequence data suggest that this pseudogene was derived via reverse
      transcription from the gene encoding the cytosolic isoform of the enzyme serine
      hydroxymethyltransferase. In addition, a heteroduplex analysis of this pseudogene
      among several species of nonhuman primate indicates a relatively high degree of
      sequence conservation.

PMID- 9156324
TI  - Data on six short-tandem repeat polymorphisms in an autochthonous Basque
      population.
AB  - Population data studies for six short-tandem repeat loci (HUMCSF1P0, HUMTPOX,
      HUMTH01, HUMHPRTB, HUMFES/FPS, and HUMvWF) were carried out on a sample of 326
      autochthonous Basques. Comparing with other European samples, we found the
      highest frequencies known so far for allele 11 of the HUMCSF1P0 locus (0.380),
      allele 10 of the HUMFES/FPS locus (0.384), and allele 17 of the HUMvWF locus
      (0.329). On the other hand, we found the lowest frequencies recorded in Europe
      for allele 12 of the HUMCSF1P0 locus (0.291), allele 7 of the HUMTH01 locus
      (0.128), and allele 11 of the HUMFES/FPS system (0.317). These results support
      the hypothesis that the Basque population is a remnant of early European
      settlers.

PMID- 9156325
TI  - Genes preserved in relatives.
AB  - The genes of an individual are said to be preserved in his relatives if they
      possess, collectively, all copies of his genes. We present a method for computing
      the probability that an individual's genes are preserved in his relatives. Using
      this method, we compute gene preservation probabilities (up to three linked loci)
      for a variety of relationships for humans and for haplodiploid species. The
      results suggest that some widely held notions in ethology and sociobiology seem
      to be questionable. From the gene preservation viewpoint, two brothers are far
      from enough to justify the sacrifice of one's own life, because the probability
      that an individual's genes are preserved in his two siblings is dismally small.
      The precise probability that an individual's genes are all preserved in a group
      of his relatives depends on the precise specification of the pedigree structure.
      We also demonstrate that, for a hymenopteran female, there is no practical
      difference, in terms of gene preservation probability, between helping her
      sisters to breed and breeding her own offspring. In fact, since the genes of her
      sister will be either lost or preserved in her nieces/nephews, it is more
      appropriate to compare the probability of preserving her genes through her own
      offspring with that through her nieces/nephews. We show that her chance of
      preserving all her genes is much higher if she chooses to breed her own offspring
      instead of helping her sister.

PMID- 9156326
TI  - Phenylketonuria mutations and linked haplotypes in the Lithuanian population:
      origin of the most common R408W mutation.
AB  - A genealogical study was performed in Lithuanian phenylketonuria (PKU) families
      with the aim of tracing the origins of the R408W/haplotype 2/VNTR3 allele. The
      relative frequency of six phenylalanine hydroxylase (PAH) mutations (R408W,
      R158Q, R261Q, G272X, IVS10nt-11g --> a, and IVS12nt1g --> a) common in Eastern
      European populations and their association with variable number of tandem repeat
      (VNTR) and short tandem repeat (STR) sites in the PAH gene were examined in 130
      PKU Lithuanian chromosomes, including 95 of Baltic, 28 of Slavonic and 7 of
      unknown origin. R408W was found to be the most frequent (70%) mutation in both
      Balts or Slavonians with a uniform frequency distribution. No statistically
      significant differences in the frequency distribution of the other mutations
      analysed were found. In Balts and Slavonians, the R408W mutation is strongly
      associated with the three-copy VNTR and the 240-bp STR allele. The frequency of
      this association is 68% in both ethnic groups. The genealogical data provided in
      this paper indicate that the most common R408W/VNTR3/STR240 allele arose in
      ancient times possibly among pre-Indo-Europeans and suggest that the high
      frequency of the R408W mutation and associated minihaplotype in Balts of
      Lithuania is due to a founder effect.

PMID- 9156327
TI  - Genotype-phenotype analysis in HbS-beta-thalassemia.
AB  - Genotypes and phenotypes were studied in 31 Turkish HbS-beta-thalassemia
      patients. In 19 patients the beta-thalassemia mutations were beta+ and in 12 the
      beta 0 phenotype. The IVSI-110 mutation was found in 45% of the patients. IVSI-1,
      beta 39, IVSII-1 and FSC8 are the genotypes associated with beta 0-thalassemia.
      Hematological data were evaluated at the time of diagnosis and 4 years after
      diagnosis. The mean HbF value was 13 +/- 7.8% at diagnosis and 9.7 +/- 7.8% 4
      years later. A significant negative correlation was observed between the age of
      the patients and the HbF value (p < 0.05). No statistically significant
      differences were observed between the mean of hematological parameters in beta(+)
      and beta 0-thalassemia patients except for the mean HbF value which were 10.7 +/
      6.9 and 15.9 +/- 7.7% in beta(+)- and beta 0-thalassemia, respectively (p <
      0.05). The study indicated that beta-thalassemia mutations in trans to the HbS
      mutation do not exert any beneficial effect on the manifestation of the disease.

PMID- 9156329
TI  - 1283 del A: a novel mutation in exon 8 of the cystic fibrosis gene.

PMID- 9156328
TI  - Extensive gene flow in human populations as revealed by protein and
      microsatellite DNA markers.
AB  - Population genetic studies are mainly based on the description of genetic
      variability and on interpopulational comparisons using genetic distance measures.
      The evolutionary dynamics of the populations are inferred from these parameters
      and accurate estimates of gene flow may be critical. The present study
      reevaluates the role of gene flow in human populations by different statistical
      methods from a number of microsatellite and protein polymorphism data. The
      estimated number of individuals exchanged per generation (Nm) was greater than 1
      in all data sets with all statistical methods. The correlation between geographic
      and genetic distances suggests a pattern of isolation by distance, characteristic
      of demographic and genetic equilibrium conditions among populations worldwide.
      Thus the high values of Nm may be interpreted as a reflection of high gene flow
      between geographically close populations. As expected, gene flow appears to exert
      a pivotal role in the genetic history of humans.

PMID- 9156330
TI  - Novel polymorphic CA/TG repeat identified in the human prostacyclin synthase
      gene.

PMID- 9156331
TI  - Maternal inheritance of atopy at the Fc epsilon RI beta locus in Japanese sibs.
AB  - Twenty-four Japanese atopic sibs with asthma and/or rhinitis were tested for
      polymorphic microsatellite repeats of Fc epsilon RI beta on chromosome 11q13.
      Significantly increased sharing of maternal alleles was found chi 2 = 5.86, p <
      0.025) while no significant sharing was found for paternal alleles. These
      findings confirm maternal inheritance of atopy at this locus in a non-Caucasian
      population.

PMID- 9156333
TI  - Effects of epidermal growth factor on growth of cell lines established from
      cynomolgus monkey hepatocytes with SV40 T antigen.

PMID- 9156332
TI  - In vitro biocompatibility test for collagen-based dressings.

PMID- 9156334
TI  - Fin cell line from isogeneic ginbuna crucian carp.

PMID- 9156335
TI  - Mineralization is more reliable in periosteum explants from size-selected chicken
      embryos.

PMID- 9156336
TI  - Successful establishment of uveal and conjunctival melanoma in vitro.

PMID- 9156337
TI  - Rapid and irreversible loss of estrogen receptor in human osteoblast-like cells
      following culture in phenol red-free medium.

PMID- 9156338
TI  - Bovine brain microvascular endothelial cells transfected with SV40-large T
      antigen: development of an immortalized cell line to study pathophysiology of CNS
      disease.

PMID- 9156340
TI  - Ratiometric measurement of intracellular pH of cultured cells with BCECF in a
      fluorescence multi-well plate reader.
AB  - A number of methods have been developed to measure intracellular pH (pHi) because
      of its importance in intracellular events. A major advance in accurate pHi
      measurement was the development of the ratiometric fluorescent indicator dye,
      2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF). We have used a
      fluorescence multi-well plate reader and a ratiometric method for determining pHi
      in primary cultures of rabbit corneal epithelial (CE) cells with BCECF.
      Fluorescence was measured at excitation wavelengths of 485 +/- 11 nm and 395 +/-
      12.5 nm, with emission detected at 530 +/- 15 nm. Cells grown in multi-well
      plates were loaded with 4 microM BCECF for 30 min at 37 degrees C. Resting pHi
      was 7.34 +/- 0.03 (2 cultures, N = 5 wells). Changes in pHi determined with the
      fluorescence multi-well plate reader after the addition and removal of NH4Cl or
      sodium lactate were comparable to changes in cells analyzed with a digitized
      fluorescence imaging system. A concentration-response relationship involving
      changes in pHi was easily demonstrated in CE cells after treatment with
      ionomycin, a calcium ionopore. Low doses of ionomycin (2.5-5 microM), produced a
      prolonged acidification; 7.5 microM ionomycin produced a transient acidification;
      and 10 microM ionomycin resulted in a slight alkalinization. We conclude that
      accurate pHi measurements can be obtained with a ratiometric method with BCECF in
      a multi-well plate reader. This technology may simplify screening studies
      evaluating effects of hormones, growth factors, or toxicants on pHi homeostasis.

PMID- 9156339
TI  - Oxidized LDL inhibits vascular endothelial cell morphogenesis in culture.
AB  - Human umbilical cord vein endothelial cells can be induced to undergo
      morphogenesis (tube formation) by phorbol ester (TPA) when cultured on or in
      three-dimensional collagen gels. Induction of morphogenesis by TPA is accompanied
      by increased activity of the collagenase gene transcription factors, ETS1 and
      API, and the elaboration of collagenase by the endothelial cells. In the present
      study, we used endothelial cell elongation as a measure of morphogenesis and
      showed that oxidized low density lipoprotein (oxLDL) inhibited endothelial cell
      migration in monolayer cultures and TPA-induced morphogenesis in collagen gels in
      a dose-dependent manner. Moreover, the inhibition was positively correlated with
      the extent of LDL oxidation. In contrast, native LDL stimulated cell migration
      and TPA-induced morphogenesis under the same culture conditions. However, in the
      absence of TPA, LDL showed no effect on EC morphogenesis. Further studies showed
      that inhibition of TPA-induced endothelial cell morphogenesis by oxLDL is
      correlated with suppression of the protein kinase C (PKC) and ETS1/AP1
      activities. The results indicated that the inhibition of endothelial cell
      morphogenesis by oxLDL is probably mediated through inhibition of the TPA
      activated PKC pathway and its subsequent suppression of the ETS1/AP1 activity.
      The results also indicated that EC migration can be mediated through PKC
      dependent and independent pathways and only the former pathway can induce EC
      morphogenesis as well.

PMID- 9156341
TI  - Identification of a subpopulation of human renal microvascular endothelial cells
      with capacity to form capillary-like cord and tube structures.
AB  - Endothelial specialization is a prominent feature within distinct capillary beds
      of organs such as mammalian kidney, yet immunological markers for functionally
      distinct subpopulations of cultured endothelial cells from tissue sources such as
      kidney have not been available. We developed a simple and reproducible isolation
      and culture procedure to recover human renal microvascular endothelial cells
      (HRMEC) from the cortex of unused donor kidneys. This procedure yields highly
      purified preparations of cells that display endothelial markers that include
      Factor VIII antigen, acetyl-LDL receptors, and determinants that bind Ulex
      europaeus lectin. HRMEC assemble into capillary-like cord and tube structures
      when plated on the surface of basement membrane-like matrix (BMM) in media
      containing phorbol myristate acetate. To further define subpopulations of HRMEC,
      we generated a panel of monoclonal antibodies and screened for those recognizing
      cell surface determinants. One monoclonal antibody recovery from this screen
      recognized a cell surface protein expressed on a subpopulation of HRMEC that we
      have designated PEC-1 (pioneer endothelial cell antigen-1). Cells expressing PEC
      1 extended long, interconnecting filopodial processes in response to phorbol
      myristate acetate and assembled into capillary-like structures when plated on
      BMM. Anti-PEC-1 immunoprecipitated proteins of 25 and 27 kDa. Magnetic bead
      separation of PEC-1 (+) cells selected cells that assemble into capillary-like
      cord and tube structures. The remaining PEC-1 (-) HRMEC population formed matrix
      adherent patches. In the kidney, the PEC-1 determinant is expressed on a small
      subpopulation of microvascular glomerular cells and is prominently expressed on
      the apical membrane of proximal tubule cells. The PEC-1 determinant discriminates
      among subpopulations of HRMEC, identifying a subpopulation that contributes to
      assembly of capillary-like structures.

PMID- 9156342
TI  - Gene transfer into mouse embryonic stem cell-derived cardiac myocytes mediated by
      recombinant adenovirus.
AB  - The main purpose of this study was to examine, for the first time, the ability of
      recombinant adenovirus to mediate gene transfer into cardiac myocytes derived
      from mouse embryonic stem (ES) cells differentiating in vitro. In addition,
      observations were made on the effect of adenovirus infection on cardiac myocyte
      differentiation and contractility in this in vitro system of cardiogenesis. ES
      cell cultures were infected at various times of differentiation with a
      recombinant adenovirus vector (AdCMVlacZ) containing the bacterial lacZ gene
      under the control of the cytomegalovirus (CMV) promoter. Expression of the lacZ
      reporter gene was determined by histochemical staining for beta-galactosidase
      activity. LacZ expression was not detected in undifferentiated ES cells infected
      with AdCMVlacZ. In contrast, infection of differentiating ES cell cultures showed
      increasing transgene expression with continued time in culture. Expression in ES
      cell-derived cardiac myocytes was demonstrated by codetection of beta
      galactosidase activity and troponin T with indirect immunofluorescence. At 24 h
      postinfection, approximately 27% of the cardiac myocytes were beta-galactosidase
      positive, and lacZ gene expression appeared to be stable for up to 21 d
      postinfection. Adenovirus infection had no apparent effect on the onset, extent,
      or duration of spontaneously contracting ES-cell-derived cardiomyocytes,
      indicating that cardiac differentiation and contractile function were not
      significantly altered in the infected cultures. The demonstration of adenovirus
      mediated gene transfer into ES-cell-derived cardiac myocytes will aid studies of
      gene expression with this in vitro model of cardiogenesis and may facilitate
      future studies involving the use of these myocytes for grafting experiments in
      vivo.

PMID- 9156343
TI  - Energy state in HT-29 cells is linked to differentiation.
AB  - The relationship between the energy source used by HT-29 cells and their state of
      differentiation was determined. Short chain fatty acids and acetoacetate were
      applied to the cells for 9 d, after which the medium was replaced with
      conventional culture medium for a further 9 d so that the permanence of the
      changes could be assessed (18 d). Glucose utilization and lactic acid,
      acetoacetate, and beta-hydroxybutyrate production by the cells were determined.
      Differentiation was assessed by the presence of the enzymes sucrase-isomaltase
      and carbonic anhydrase 1, as well as morphological changes of the cells. By
      tracing carbon from acetate, propionate, and butyrate through the cells, it was
      found that the carbon from the short-chain fatty acids was fluxed into
      acetoacetate. Significant amounts of acetoacetate were released by the propionate
      treated culture after 9 d and the acetate-, propionate-, valerate-, and caproate
      treated cultures after 18 d. A significant positive correlation was found between
      acetoacetate synthesis and differentiation. Acetoacetate applied to HT-29 cells
      also induced their differentiation. The acetate-, butyrate-, valerate-,
      isovalerate-, and caproate-treated cells underwent terminal differentiation,
      while the propionate- and isocaproate-treated cultures underwent programming
      events. We, therefore, conclude that HT-29 cells utilize short chain fatty acids
      in preference to glucose, metabolize these to ketones, thereby raising the energy
      state and effecting the observed morphological and functional changes in the
      cells.

PMID- 9156345
TI  - Statistical methods for estimating doubling time in in vitro cell growth.
AB  - Doubling time has been widely used to represent the growth pattern of cells. A
      traditional method for finding the doubling time is to apply gray-scaled cells,
      where the logarithmic transformed scale is used. As an alternative statistical
      method, the log-linear model was recently proposed, for which actual cell numbers
      are used instead of the transformed gray-scaled cells. In this paper, I extend
      the log-linear model and propose the extended log-linear model. This model is
      designed for extra-Poisson variation, where the log-linear model produces the
      less appropriate estimate of the doubling time. Moreover, I compare statistical
      properties of the gray-scaled method, the log-linear model, and the extended log
      linear model. For this purpose, I perform a Monte Carlo simulation study with
      three data-generating models: the additive error model, the multiplicative error
      model, and the overdispersed Poisson model. From the simulation study, I found
      that the gray-scaled method highly depends on the normality assumption of the
      gray-scaled cells; hence, this method is appropriate when the error model is
      multiplicative with the log-normally distributed errors. However, it is less
      efficient for other types of error distributions, especially when the error model
      is additive or the errors follow the Poisson distribution. The estimated standard
      error for the doubling time is not accurate in this case. The log-linear model
      was found to be efficient when the errors follow the Poisson distribution or
      nearly Poisson distribution. The efficiency of the log-linear model was decreased
      accordingly as the overdispersion increased, compared to the extended log-linear
      model. When the error model is additive or multiplicative with Gamma-distributed
      errors, the log-linear model is more efficient than the gray-scaled method. The
      extended log-linear model performs well overall for all three data-generating
      models. The loss of efficiency of the extended log-linear model is observed only
      when the error model is multiplicative with log-normally distributed errors,
      where the gray-scaled method is appropriate. However, the extended log-linear
      model is more efficient than log-linear model in this case.

PMID- 9156344
TI  - Growth requirements and neoplastic transformation of two types of normal human
      breast epithelial cells derived from reduction mammoplasty.
AB  - A chemically defined culture medium was developed to support the growth of two
      distinctly different types of normal human breast epithelial cells (HBEC) derived
      from reduction mammoplasty. Type I cells expressed luminal epithelial cell
      markers and were deficient in gap junctional intercellular communication (GJIC),
      whereas Type II cells expressed basal epithelial cell markers and were efficient
      in GJIC. In this study, we examined and compared the growth factor and hormone
      requirements of these two types of cells and a series of cell lines that were
      obtained by sequential transfection with SV40 DNA (extended lifespan,
      nontumorigenic), treatment with 5-bromodeoxyuridine (BrdU)/black light (immortal
      and weakly tumorigenic), and infection of a virus carrying the neu oncogene
      (highly tumorigenic). Growth of Type I cells was inhibited by withdrawing
      epidermal growth factor (EGF), hydrocortisone (HC), or insulin (INS) from the
      culture media, but was enhanced by fetal bovine serum (FBS) supplementation.
      Growth of Type II cells was inhibited by withdrawal of EGF, HC, or INS from the
      media, and was inhibited by FBS supplementation. Withdrawal of human transferrin
      (HT) or 17 beta-estradiol (E2) from the media did not alter the growth of Type I
      or Type II cells. SV40 transfected Type I cell lines still required EGF, HC, or
      INS for optimal growth. However, the highly tumorigenic cell line did not show a
      growth dependence on EGF, HC, or INS but did appear to require HT and 3,3',5
      triiodo-D.L. thyronine (T3) for optimal growth. In addition, FBS stimulated the
      growth of these cell lines. Thus, this study shows that Type I HBEC are
      distinctly different from Type II HBEC in growth response to FBS and that
      neoplastically transformed Type I cells could become growth factor and hormone
      independent.

PMID- 9156346
TI  - Transcriptional regulation of the TGF-beta 2 gene in choriocarcinoma cells and
      breast carcinoma cells: differential utilization of Cis-regulatory elements.
AB  - Previous studies have shown that the transcription of the TGF-beta 2 gene is
      controlled by at least one negative and two positive regulatory regions in
      differentiated cells derived from both embryonal carcinoma cells and embryonic
      stem cells. The use of TGF-beta 2 promoter/reporter gene constructs has also
      identified a CRE/ATF motif near the TATA box that appears to heavily influence
      the transcription of the TGF-beta 2 gene. In this study, two choriocarcinoma cell
      lines, JAR and JEG-3, and the breast cancer cell line, MCF-7, were used to
      determine whether differences exist in the transcriptional regulation of the TGF
      beta 2 gene. We demonstrated that both similarities and differences exist in the
      transcriptional regulation of this gene. Common to all cells examined to date,
      the positive regulatory region just upstream of the TATA box contains an
      essential CRE/ATF motif that binds at least one transcription factor, ATF-1, in
      gel mobility shift assays. However, we did not detect ATF-2 binding to this site
      with any of the nuclear extracts used. We also determined that the effect of the
      region between -187 and -78 (relative to the transcription start site) is cell
      type dependent. Previous studies have shown that this region acts to reduce the
      activity of the TGF-beta 2 promoter in differentiated cells derived from
      embryonal carcinoma cells and embryonic stem cells. In direct contrast, this
      region acts as a strong positive regulatory region in JAR, JEC-3, and MCF-7
      cells. The mechanisms responsible for these differing effects remain to be
      established. Interestingly, this region does not appear to contain sequence
      motifs that bind known transcription factors. Thus, this region is likely to bind
      one or more novel transcription factors or contain novel recognition sites for
      known transcription factors.

PMID- 9156347
TI  - Growth and differentiation of periodontal ligament-derived cells in serum-free
      defined culture.
AB  - We have developed a serum-free medium for the growth and differentiation of
      periodontal ligament-derived cells (PLC). In addition, the expression of both
      fibroblast growth factor (FGF) and FGF receptor (FGFR) in the PLC was
      investigated by immunohistochemical examination, heparin affinity chromatography
      (HAC), and reverse transcription-polymerase chain reaction (RT-PCR) analysis.
      Optimal growth of the cells was achieved in Iscove's modified Dulbecco's medium
      supplemented with insulin, transferrin, 2-mercaptoethanol, 2-ethanolamine, sodium
      selenite, and oleic acid in type-I collagen-coated dishes. Both FGF-1 and FGF-2
      stimulated cell growth and inhibited differentiation as measured by inhibition of
      alkaline phosphatase activity of the cells. An immunohistochemical analysis of
      FGF-1 and FGF-2 revealed that immunoreactive FGF-1 and FGF-2 were detected
      predominantly in the cytoplasm of growing cells. In addition, perinuclear FGF-1
      staining and nuclear FGF-2 staining were observed in the same growing cells. In
      contrast, a faint diffuse staining of FGF-1 and FGF-2 was detected in cytoplasm
      of the confluent differentiated cells. The 2.15 M NaCl eluate from HAC of the
      cell extracts exhibited growth-promoting activities for the PLC, and it also
      stimulated the growth of human umbilical vein-derived endothelial cells and
      inhibited binding of [125I]-FGF to its receptors, indicating the cells produced
      FGFs or FGF-like growth factors. RT-PCR analysis revealed that the cells
      expressed FGFR-1 mRNA but not mRNAs for FGFR-2, FGFR-3 and FGFR-4 mRNA. These
      results suggest that the FGF-FGFR-1 system plays an important role in the growth
      and differentiation of periodontal ligament-derived cells.

PMID- 9156348
TI  - 1,25-dihydroxyvitamin D3 and agents that increase intracellular adenosine 3',5'
      monophosphate synergistically inhibit fibroblast proliferation.
AB  - Agents that increase intracellular cAMP (cAMP elevating agents) and 1, 25(OH)2D3
      inhibit the proliferation of many cell types. We investigated the combined effect
      of 1,25(OH)2D3 and cAMP elevating agents on exponentially growing mouse 3T3
      fibroblasts. The following cAMP elevating agents were used: theophylline and
      pentoxyfilline, which inhibit cAMP-dependent phosphodiesterase; prostaglandin E2
      which activates adenylate cyclase by a receptor-mediated mechanism; forskolin,
      which directly stimulates adenylate cyclase; and the cell permeable cAMP analogs
      8-bromo cAMP and N6 benzoyl cAMP. 1,25(OH)2D3 and cAMP elevating agents were
      added to exponentially growing fibroblasts cultured in 96-well microtiter plates
      and cell number was monitored 3-7 d later. 1,25(OH)2D3 and the cAMP elevating
      agents as single agents inhibited the growth of the 3T3 cells. The combined
      treatment of the fibroblasts with 1,25(OH)2D3 and the cAMP elevating agents
      resulted in an antiproliferative effect that was more than additive. The
      synergistic interaction depended on the dose of 1,25(OH)2D3 and was apparent
      already at 10(-8) M of the hormone. The specificity of the effect of 1,25(OH)2D3
      was demonstrated by the finding that 24,25-dihydroxyvitamin D3, a vitamin D
      metabolite with low affinity for the vitamin D receptor, did not affect the
      antiproliferative effect of cAMP elevating agents. From the synergistic
      interaction between 1,25(OH)2D3 and the cell permeable cAMP analogs, we infer
      that the site of interaction between the two signaling pathways is distal to the
      cAMP generating and degrading machinery.

PMID- 9156349
TI  - Cytolytic activity of Bacillus thuringiensis CryIC and CryIAc toxins to
      Spodoptera sp. midgut epithelial cells in vitro.
AB  - A sensitive lactate dehydrogenase (LDH) assay was modified to determine the
      cytolytic activity of Bacillus thuringiensis CryIC and CryIAc delta endotoxins to
      viable collagenase-dissociated midgut epithelial cells (MEC) from larvae of
      Spodoptera frugiperda and Spodoptera exigua. The MEC preparations from these
      Spodoptera sp. consisted predominantly of columnar cells (65-75%) and goblet
      cells (25-35%). Time course microscopy experiments indicated that only the
      columnar cells became swollen during CryIC toxin incubation. Also, comparative
      cytotoxicity studies were run with cell lines of nonmidgut origin established
      from S. frugiperda (SF21AE) and S. exigua (SEUCR1A). Optimum conditions for the
      cytotoxicity assay were similar for MEC and cell lines of both species, and were
      met in an assay in which 0.1-ml cell concentrations (8.5 +/- 0.5 x 10(4) cells)
      were incubated with toxin dilutions (0.01-20 micrograms) for 1 h at 24 degrees C
      at a final pH of 7.8. The Spodoptera sp. MEC were twofold more sensitive to CryIC
      (68% lysis) than CryIAc (32% lysis) at optimum toxin levels (2.5-5 micrograms).
      Also, the SEUCR1A cells were more sensitive (2.3-fold) to CryIC (70% lysis) than
      CryIAc (30% lysis) at optimum toxin levels of 5-10 micrograms. The SF21AE cells,
      however, were twofold less sensitive to CryIC (30% lysis) than SEUCR1A cells and
      response to CryIAc and CryIC was similar. Immunoblot analysis of either
      Spodoptera sp. MEC or brush border membrane vesicles (BBMV) identified seven
      CryIC binding proteins with molecular mass of 137, 120, 115, 68, 65, 63, and 45
      kDa. Occasionally, a 148-kDa protein band was observed. The CryIAc toxin bound to
      two proteins on MEC and BBMV with molecular mass of 137 and 120 kDa.

PMID- 9156350
TI  - Effects of lidocaine, ajmaline, and diltiazem on ventricular defibrillation
      energy requirements in isolated rabbit heart.
AB  - The majority of patients with implanted cardioverter defibrillators (ICD) require
      antiarrhythmic (AR) drugs. ARs may increase defibrillation energy requirements.
      This study investigated the effects of lidocaine, ajmaline, and diltiazem on
      ventricular defibrillation energy needs. In 24 isolated rabbit hearts, the 50 and
      80% successful defibrillation energy (ED50, ED80) was calculated in four phases:
      predrug baseline condition (phase 1), and phases 2, 3, and 4 with increasing
      concentrations of lidocaine, ajmaline, diltiazem (n = 18). Control experiments (n
      = 6) with only Tyrode's solution infusion indicated that the preparation was
      stable over time. Defibrillation energy requirements significantly (p < 0.05)
      increased with all ARs. Low, medium, and high lidocaine concentrations increased
      ED50 and ED80 to 146, 223, and 312% and 139, 207, and 285%, respectively.
      Ajmaline increased ED50 and ED80 to 133, 175, and 251% and 135, 208, and 285%,
      respectively. Diltiazem increased ED50 and ED80 by 175, 236, and 334% and 158,
      212, and 286%, respectively. The results of this study demonstrate a dose
      dependent increase in defibrillation energy requirements by using lidocaine,
      diltiazem, and ajmaline. In patients with ICDs, administration of these drugs
      might cause a critical increase in defibrillation energy requirements, resulting
      in device failure.

PMID- 9156351
TI  - Beta-adrenoceptor stimulation-mediated preconditioning-like cardioprotection in
      perfused rat hearts.
AB  - To determine whether adrenergic stimulation induces preconditioning-like
      cardioprotection, rat hearts were perfused for 2 min with either norepinephrine,
      phenylephrine, or isoproterenol followed by 10-min drug-free perfusion. Then the
      hearts were subjected to 40-min ischemia and 30-min reperfusion. Little recovery
      of left ventricular developed pressure (LVDP) and loss of the myocardial creatine
      kinase (CK) during reperfusion were observed in the drug-untreated heart.
      Preperfusion with norepinephrine (0.25 microM) or isoproterenol (0.25 microM),
      but not phenylephrine (10 microM), resulted in a better recovery of LVDP in the
      postischemic reperfused heart and a reduction in CK release during reperfusion. A
      similar improvement of postischemic cardiac contractile dysfunction and CK loss
      was seen in the heart subjected to 5-min ischemia followed by 5-min reperfusion
      (ischemic preconditioning) before the prolonged period of ischemia/reperfusion.
      Pretreatment with timolol, a beta-adrenoceptor blocker, abolished the protective
      effect of norepinephrine, whereas pretreatment with bunazosin, an alpha 1
      adrenoceptor blocker, did not affect the protective effect of isoproterenol. The
      results suggest that a brief period of stimulation of cardiac beta-adrenoceptor
      exerts the preconditioning-mimetic protective effect against postischemic
      contractile dysfunction in perfused rat hearts.

PMID- 9156352
TI  - SC-52458, an orally active angiotensin II-receptor antagonist: inhibition of
      blood pressure response to angiotensin II challenges and pharmacokinetics in
      normal volunteers.
AB  - This study was designed to assess in normal volunteers the potency, efficacy, and
      tolerability of the new nonpeptidic, orally active, angiotensin (Ang) II subtype
      1 (AT1)-receptor antagonist SC-52458. After a randomized, single-blind, placebo
      controlled protocol, two groups of eight healthy men ingested placebo or
      increasing single oral doses (10, 25, and 50 mg or 100, 150, and 200 mg) of SC
      52458. Finger blood pressure (BP) was continuously monitored (Finapres), and BP
      response to repeated intravenous challenges with Ang II was compared with
      baseline BP response to the same dose of Ang II. Up to 24 h after drug intake,
      effects on plasma renin activity (PRA), Ang II, and aldosterone and
      pharmacokinetics were estimated. One, 4, and 10 h after the 200-mg dose,
      diastolic BP response to Ang II challenges was decreased from 30.3 to 2.6 mm Hg
      (mean +/- SEM; n = 8; i.e., to 8.3 +/- 1.1% of baseline response), 10.1 mm Hg
      (35.4 +/- 1.8%), and 17.5 mm Hg (58.7 +/- 1.8%), respectively. SC-52458 produced
      dose-related increases in PRA and Ang II concentrations < or = 10 h after drug
      intake. Plasma aldosterone concentrations tended to be decreased for < or = 24 h
      after SC-52458 doses of > or = 100 mg. No drug-related side effects were
      observed. The pharmacokinetics were linear over the dose range of 10-150 mg (t1/2
      = 1.14-2.39 h). Efficacy was dose dependent, with a peak effect after 1 h. In
      conclusion, the novel AT1-receptor antagonist SC-52458 is well tolerated and
      orally active. It produces a rapid-onset inhibition of the renin-angiotensin
      system and reduces BP response to Ang II for > or = 10 h. These characteristics
      promise strong antihypertensive properties for SC-52458.

PMID- 9156353
TI  - Comparative vasoconstrictor effects of angiotensin II, III, and IV in human
      isolated saphenous vein.
AB  - Elevated levels of angiotensin (Ang II) and its degradation products angiotensin
      III (Ang III) and angiotensin IV (Ang IV) may contribute to the regulation of
      vascular tone under various clinical circumstances. We investigated the
      contractile effects of Ang III and Ang IV in endothelium-denuded human saphenous
      vein (SV) preparations and compared them with those of Ang II. The veins were
      suspended in organ chambers, and changes in isometric force were recorded. Ang II
      (0.1-100 nM), Ang III (1 nM-3 microM), and Ang IV (0.3 microM-0.1 mM) caused
      concentration-dependent contractions with comparable maximal responses (Emax).
      Ang III was 16 times less active than Ang II, whereas Ang IV was approximately
      2,700-fold less potent than Ang II. In the presence of the aminopeptidase-A and 
      M inhibitor amastatin (10 microM), the potencies of Ang III and Ang IV were
      increased by approximately 16 and 12 times, respectively, although no changes of
      Ang II potency were observed. The AT1-selective Ang II receptor antagonist
      losartan (10 and 100 nM) but not the AT2-selective antagonist PD123177 (1
      microM), shifted the concentration-response curves (CRC) for the angiotensin
      peptides to the right in a parallel manner. Preincubation with indomethacin (10
      microM), a cyclooxygenase inhibitor, did not influence the CRCs for any of the
      angiotensin peptides studied. Tachyphylaxis was investigated by constructing a
      second series of CRCs for the angiotensin peptides after an interval of 60 min.
      Ang II showed strong tachyphylaxis (the Emax value of the second Ang II CRC was
      approximately 50% of the first), whereas Ang III and Ang IV did not. Our results
      indicate that in endothelium-denuded human SV, both Ang III and Ang IV are less
      potent but similarly efficacious vasoconstrictor agents compared with Ang II.
      Endogenous aminopeptidase activity may counteract the effects of the angiotensin
      peptides. The contractile responses to all three peptides are mediated via AT1
      receptors but not AT2-receptors.

PMID- 9156354
TI  - Effect of chronic oral supplementation with alpha-tocopherol on myocardial
      stunning in the dog.
AB  - Recent clinical and experimental studies have suggested that antioxidant
      supplements might actually have harmful as well as beneficial effects in the
      setting of cardiovascular disease. The mechanisms underlying the beneficial
      effects of the various antioxidants are poorly understood in humans. Reperfusion
      associated myocardial injury, and particularly the phenomenon of stunning, is
      important because it occurs in clinical settings and may condition the prognosis
      after short ischemic insult. We studied the effects of chronic (3 months) alpha
      tocopherol supplementation with a large oral dose (500 mg daily) on myocardial
      contractility (stunning) and ventricular arrhythmias in a dog model of short
      ischemia followed by reperfusion. Twenty dogs were randomized to either an alpha
      tocopherol supplemented or a control group. After 3 months, dogs were
      anesthetized and underwent a 20-min coronary artery occlusion followed by
      reperfusion. Myocardial regional blood flow was measured by the radioactive
      microsphere technique and myocardial contractility by sonomicrometry. Plasma
      alpha-tocopherol was measured by high-performance liquid chromatography in all
      dogs. Twelve dogs (seven supplemented and five controls) developed ventricular
      fibrillation at reperfusion, showing no difference between groups. Hemodynamic
      parameters, blood flow in the ischemic area (collateral flow), and area at risk
      were similar in the two groups. Regional systolic segment shortening in the
      ischemic area was similar during ischemia and reperfusion in both groups,
      representing 41 +/- 15% (mean +/- SEM) of baseline contractility in controls and
      51 +/- 8% in supplemented dogs after 150 min of reperfusion. Plasma alpha
      tocopherol level was higher in supplemented than in controls (19.1 +/- 1.6 and
      6.9 +/- 0.6 mg/L; p < 0.001). Thus a long-term large dose of alpha-tocopherol had
      no significant effect on postischaemic ventricular arrhythmias and dysfunction
      (myocardial stunning) in this canine model. These data suggest that if alpha
      tocopherol supplementation might be useful to improve the prognosis of coronary
      patients, it is likely not by interfering with the stunning phenomenon.

PMID- 9156355
TI  - Mechanism of action of human calcitonin gene-related peptide in rabbit heart and
      in human mammary arteries.
AB  - We investigated the effects of human calcitonin gene-related peptide (CGRP) on
      isolated rabbit hearts to evaluate the mechanisms responsible for the
      vasodilatory action of the peptide on the coronary district, monitoring
      contemporaneously the effects on left ventricular pressure (LVP) and heart rate
      (HR). We also evaluated the reactivity of the human internal mammary artery (IMA)
      to excitatory drugs acting with different mechanisms and the inhibitory response
      to CGRP in comparison with the commonly used vasodilatory agents. The peptide
      induced a slight inhibitory effect on the basal coronary perfusion pressure
      (CPP), whereas it was ineffective on the inotropism and chronotropism. A more
      detectable coronary vasodilation was evident when CPP was increased by
      spasmogenic agents [vasopressin, methoxamine, Bay K 8644, and prostaglandin F2
      alpha (PGF2 alpha)]. This inhibitory effect was dose dependent (10(-11)-10(-8) M)
      and apparently not specific, occurring to the same extent on different stimuli.
      Forskolin (10(-8) M), an adenylate-cyclase activator, and indomethacin (1.4 x 10(
      5) M), a cyclooxygenase inhibitor, did not modify the spasmolytic activity of
      CGRP on precontracted coronary smooth muscle. The experiments performed on the
      segments of IMA, used for myocardial revascularization of patients affected by
      coronary diseases, have shown an evident spasmolytic action of CGRP on increased
      vascular tone induced by KCl (90 mM), noradrenaline (10(-5) M), serotonin (10(-6)
      M), and angiotensin II (10(-6) M). These inhibitory responses of CGRP on the
      spasmogenic compounds disappeared when the endothelial function of IMA, validated
      by the acetylcholine test, was abolished by mechanical ablation. A series of IMA
      segments was incubated (30 min) with N(G)-monomethil-L-arginine (L-NMMA), which
      inhibits nitric oxide (NO) synthase. In these experiments, the peptide failed to
      induce the vasodilation, suggesting that its action may be related to synthesis
      of NO. All these results show that CGRP is able to induce a potent vasodilatory
      action on different vessels of humans (internal mammary artery) and animals
      (rabbit coronary arteries). In particular the data obtained from IMA demonstrated
      that the vasorelaxant effect was related to synthesis of NO, one of the most
      studied endothelium-derived relaxing factors (EDRFs).

PMID- 9156356
TI  - Electrophysiologic effects of SD-3212, a new class I antiarrhythmic drug, on
      canine atrial flutter and atrial action-potential characteristics.
AB  - SD-3212 (levo-semotiadil fumarate) is a newly developed compound that exhibits
      potent antiarrhythmic activity because of its inhibitory action on sodium and
      calcium channels. In animal models, SD-3212 suppressed ventricular
      tachyarrhythmias, but the effects of this drug on atrial tachyarrhythmias have
      not been reported. We investigated the electrophysiologic effects of SD-3212 on
      canine atrial flutter induced after placement of the intercaval obstacle and on
      atrial action-potential characteristics. In all seven dogs, SD-3212 (1.9 +/- 0.3
      mg/kg) terminated atrial flutter after significant increase in atrial flutter
      cycle length from 126 +/- 5 to 166 +/- 14 ms (increase, 31 +/- 8%; p < 0.005). SD
      3212 increased right atrial effective refractory period (RAERP) significantly
      from 126 +/- 7 to 149 +/- 11 ms at a basic cycle length of 300 ms. The increases
      in RAERP after SD-3212 at basic cycle lengths of 300, 200, and 150 ms did not
      differ (increase, 18 +/- 4%, 17 +/- 3%, and 19 +/- 3%, respectively). Interatrial
      conduction time (IACT) was prolonged after SD-3212 from 63 +/- 4 to 81 +/- 6 ms
      (increase, 31 +/- 6%) at a basic cycle length of 150 ms. Prolongation of IACT was
      frequency dependent. The plasma concentration of SD-3212 after the termination of
      atrial flutter was 187 +/- 56 ng/ml in four dogs tested. In vitro study by using
      standard microelectrode techniques showed SD-3212 at concentrations of 1-3 microM
      significantly prolonged action-potential duration at 90% repolarization. Vmax was
      decreased by SD-3212 in a concentration-dependent manner (0.3-3 microM), and the
      inhibitory effect on Vmax was greatest at the highest stimulation frequency of
      3.3 Hz. These results indicate that a new antiarrhythmic drug, SD-3212, is
      effective in interrupting canine atrial flutter, possibly by suppressing atrial
      conduction, and might be effective for the treatment of clinical atrial
      tachyarrhythmias.

PMID- 9156357
TI  - Beta-adrenergic stimulation enhances left ventricular diastolic performance in
      normal subjects.
AB  - To determine the effects of beta-adrenergic stimulation on transmitral Doppler
      echocardiography flow characteristics of left ventricular diastolic filling, we
      studied 10 healthy volunteers aged 23-31 years (mean age, 26.6 years) during
      intravenous infusion of isoprenaline in consecutive steps of 0.1, 0.2, 0.4, 0.75,
      and 1.5 micrograms/min (each for 15 min). Saline control infusion was given in
      the same manner in a crossover and blinded protocol. Compared with the infusion
      of placebo, stepwise increasing doses of isoprenaline caused a dose-related
      increase in early and late diastolic filling velocities and velocity-time
      integrals, a lengthening of the acceleration time, and a shortening of the
      deceleration and filling time. The chosen method proved highly sensitive, as
      statistically significant changes were detectable at the lowest dose of 0.1
      microgram/min for all variables except velocity-time integral of late filling and
      deceleration time (> or = 0.2 microgram/min). The effects related to dose in a
      log-linear fashion except for the lengthening of the acceleration time (early
      ceiling), the increase of peak early filling velocity (increased steepness at
      higher doses), and the shortening of the filling time. Inclusion of the
      associated increases in heart rate and systolic blood pressure and the decrease
      in diastolic blood pressure blunted all treatment contrasts except for the
      increase of peak early filling velocity. In addition, the hemodynamics with
      respect to heart rate and loading conditions were not altered at low dosages of
      drug (< 0.4 microgram/min). Effects of at least the peak early filling velocity
      must be interpreted as an active adrenergically mediated myocardial relaxation
      process. These findings have potentially important clinical implications for this
      noninvasive, readily available, and convenient technique in clinical
      pharmacology, stress testing, and possibly therapeutic interventions in diastolic
      dysfunction in humans.

PMID- 9156358
TI  - Pressor and hormonal responses to angiotensin I infusion in healthy subjects of
      different angiotensin-converting enzyme genotypes.
AB  - The effects of incremental infusion of angiotensin I on pressor and hormonal
      responses in relation to the angiotensin-converting enzyme (ACE) genotype were
      compared in healthy men of genotype DD (n = 8) and II (n = 8). The R(d)25 was the
      rate of angiotensin I infusion required to achieve a 25-mm Hg increase in
      diastolic pressure, and the R(s)25, that which caused a 25-mm Hg increase in
      systolic pressure. Changes in heart rate (HR25) were analysed at the time the
      R(d)25 was achieved. Serum ACE activity and plasma renin, angiotensin II, and
      aldosterone concentrations were measured at the start and end of the angiotensin
      I infusion. Serum ACE activity differed significantly between the genotypes with
      significantly higher mean values in DD subjects (46.3 +/- SEM 5.2 U/L) than II
      subjects (12.3 +/- 1.4 U/L; p < 0.001). Age, weight, and baseline blood pressure,
      heart rate, urinary sodium excretion, plasma renin, angiotensin II, and
      aldosterone concentrations did not differ between genotypes. The geometric mean
      infusion rates of angiotensin I required to achieve R(d)25 were 2.53
      micrograms/min in II subjects and 2.67 micrograms/min in DD subjects (ratio of
      infusion rates, 0.95; 95% CI, 0.44-2.02; p > 0.05). The corresponding infusion
      rates for systolic blood pressure (R(s)25) were 4.47 micrograms/min in II
      subjects and 3.39 micrograms/min in DD subjects (ratio, 1.32; 95% CI, 0.49-3.55;
      p > 0.05). At the time of R(d)25, changes in heart rate from baseline were +1.2
      beats/min for DD subjects and -9.5 beats/min for II subjects (diff II-DD = 10.7
      beats/min; 95% CI, 6.7-14.8; p = 0.01). There were no differences in plasma
      renin, angiotensin, and aldosterone responses to angiotensin I infusion between
      the DD and II genotypes. We showed no difference in blood pressure or renin
      angiotensin-aldosterone system responses to infusion of angiotensin I related to
      the deletion or insertion allele of the ACE gene polymorphism, but the study has
      insufficient power to exclude with certainty such differences. There was a
      significant difference between II and DD subjects in the chronotropic response to
      angiotensin I infusion.

PMID- 9156359
TI  - Studies of the cellular mechanisms underlying the vasorelaxant effects of
      rutaecarpine, a bioactive component extracted from an herbal drug.
AB  - We conducted studies to investigate the nature and underlying mechanisms of the
      vascular effects of rutaecarpine (Rut), an alkaloid isolated from the Chinese
      herbal drug Evodia rutaecarpa. By using largely the effects on phenylephrine (PE)
      induced contraction in the isolated rat aorta as the experimental index and by
      comparison with several known vascular muscle relaxants such as acetylcholine
      (ACh), histamine, and A23187, Rut relaxed PE-precontracted aorta in concentration
      (10(-7)-10(-4) M) and endothelium-dependent manners. Studies with appropriate
      antagonists indicated that this was coupled to nitric oxide (NO) and guanylyl
      cyclase. Extracellular Ca2+ removal and treatment with the intracellular Ca2+
      antagonist, 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), suggested
      that influx of extracellular Ca2+ was the major factor contributing to the action
      of Rut. Pertussis toxin suppressed the relaxation potency of histamine but had no
      effects on the actions of Rut. NaF, the G proteins activator, attenuated the
      actions of ACh, but only minimally affected Na-NP, A23187, and Rut. 1-[6-{[17
      beta-3-methoxyestra-1,2,3(10)-trien-17-yl]amino} hexyl]-1H-pyrrole-2,5-dione
      (U73122), the phospholipase C inhibitor, again suppressed the actions of ACh but
      had few effects on A23187 and Rut. Taken together, these results suggest that
      these vasorelaxants had different cellular mechanisms and that neither pertussis
      toxin-sensitive Gi protein, other G proteins, nor phospholipase C activation was
      involved in the cellular response to rutaecarpine.

PMID- 9156360
TI  - Antiischemic and antiarrhythmic activities of some novel alinidine analogs in the
      rat heart.
AB  - The antiischemic and antiarrhythmic effects of alinidine and a number of novel
      alinidine analogs were examined by using perfused rat-heart models. In the
      isolated working rat heart, the alinidine analog TH91:21 (10 microM; a butyl
      derivative) significantly increased the postischemic recovery of the heart in
      terms of both power and efficiency when compared with the control group. In the
      in situ perfused heart model, this same compound, along with TH91:22 (10 microM;
      a pentyl derivative) also significantly reduced the severity of both ischemia-
      and reperfusion-induced arrhythmias in both paced and unpaced hearts. Thus this
      study is the first to demonstrate the potent antiarrhythmic efficacy of two novel
      alinidine analogs TH91:21 and TH91:22, with TH91:21 also demonstrated to be a
      potent antiischemic agent in the isolated working rat heart. Although the mode of
      action of these compounds remains unclear, results from this study suggest that
      it is not simply a result of bradycardia or blockade of KATP channels, two
      actions these compounds possess. These compounds thus possess a novel and
      beneficial pharmacologic profile worthy of further study.

PMID- 9156361
TI  - Effects of short-term administration of sublingual nifedipine on coronary
      arterial wall elastic properties: evaluation by intravascular ultrasound.
AB  - Intravascular ultrasound is suited to measure coronary cross-sectional anatomy.
      Therefore the regional coronary wall elasticity was evaluated by examining the
      response to nifedipine. In 20 patients, coronary ostial pressure (P) and
      intravascular ultrasound images were simultaneously recorded before and after
      sublingual administration of 10 mg nifedipine. We identified the perimeter of the
      vessel wall, with normal or atherosclerotic plaque, on ultrasound image. At the
      atherosclerotic site, we measured segmental perimeter (S) for each normal or
      plaque segment. The ratio of the individual segment length (delta S/delta P) and
      cyclic variation of cross-sectional area (delta A/delta P) per mm Hg increase in
      P were calculated. Nifedipine decreased pressure (133/79-120/73 mm Hg) and
      increased heart rate (79-82 beats/min). After nifedipine, delta A/delta P
      increased from 8.5 +/- 10.2 x 10(-3) to 16.5 +/- 14.4 x 10(-3) mm2/mm Hg at 20
      normal sites (p = 0.005) but was unchanged at 17 atherosclerotic sites (6.6 +/-
      7.0 x 10(-3) to 6.7 +/- 7.1 x 10(-3) mm2/mm Hg). Nifedipine increased delta
      S/delta P in normal segments (4.5 +/- 8.7 x 10(-3) to 9.9 +/- 10.9 x 10(-3) mm/mm
      Hg; p = 0.02) but produced no change in segments with calcified or soft plaque (
      1.1 +/- 0.3 x 10(-3) to 1.4 +/- 1.6 x 10(-3) mm/mm Hg and 5.0 +/- 3.6 x 10(-3) to
      6.1 +/- 4.8 x 10(-3) mm/mm Hg, respectively). This study demonstrated that
      nifedipine increases regional coronary arterial elasticity at normal segments but
      not at that containing mildly atherosclerotic segment, and likely that the
      arterial wall function indicated by the response to nifedipine was impaired at an
      early stage of atherosclerosis.

PMID- 9156362
TI  - Effects of putative K+ channel blockers on beta-adrenoceptor-mediated
      vasorelaxation of rat mesenteric artery.
AB  - The aim of our study was to investigate the contribution of Ca(2+)-activated K+
      channels (KCa channels) and ATP-sensitive K+ channels (KATP channels) to the
      vasodilator responses to beta-adrenoceptor agonists in the rat isolated
      mesenteric artery. Isoprenaline and fenoterol concentration-dependently relaxed
      the phenylephrine-precontracted endothelium-intact arterial rings with 50%
      inhibitory concentration (IC50) of 0.0314 +/- 0.027 microM (n = 20) and 0.40 +/-
      0.04 microM (n = 11), respectively. Charybdotoxin (100 nM) displaced the
      isoprenaline or fenoterol logarithmic concentration-relaxation curve to the right
      in the absence and presence of endothelium. In contrast, glibenclamide (10
      microM) did not affect the effects of isoprenaline and fenoterol, whereas
      glibenclamide (3 microM) significantly inhibited the cromakalim-induced
      vasorelaxation. Neither charybdotoxin (100 nM) nor glibenclamide (10 microM)
      influenced the vasorelaxation induced by forskolin. Ba2+, a nonselective blocker
      of K+ channels, inhibited the relaxant effects of isoprenaline and forskolin.
      These results suggest that KCa but not KATP channels contribute to beta
      adrenoceptor-mediated vasodilator response in rat mesenteric artery, and cyclic
      adenosine monophosphate (cAMP) might not be involved in regulation of the
      activity of KCa channels.

PMID- 9156363
TI  - Felodipine and amlodipine in stable angina pectoris: results of a randomized
      double-blind crossover trial.
AB  - A randomized, double-blind, crossover study tested the antiischemic and
      antianginal efficacy of felodipine, extended-release 5-10 mg, versus amlodipine,
      5-10 mg once daily. Fifty-two patients with documented exercise-induced angina
      pectoris and myocardial ischemia during 24-h electrocardiographic monitoring were
      included in the study. Forty-seven patients completed the 8-week treatment
      period, whereas five patients withdrew from the study. The mean number of
      ischemic episodes/24 h was reduced from 19.9 at baseline to 2.3 during amlodipine
      and to 2.4 during felodipine; the total duration of ischemic episodes decreased
      from 69.8 min/24 h to 15.2 min and 15.5 min during amlodipine and felodipine,
      respectively (for both variables, p = 0.83 and p = 0.53 between treatments, and
      for both treatments, p < 0.001 compared with baseline). Eighteen (38%) patients
      receiving amlodipine and 19 (40%) patients receiving felodipine showed no ST
      segment depression during treatment. Maximal ST-depression was reduced from an
      average of 2.1 mm to 1.1 and 1.2 mm on amlodipine and felodipine, respectively (p
      = 0.68 between treatments and p < 0.001 compared with baseline). Mean heart rate
      remained unchanged compared with baseline. Anginal attacks were reduced from
      16.4/week at baseline to 4.7/week with amlodipine and to 4.3/week with felodipine
      (p = 0.26 between treatments, and p < 0.001 vs. baseline). Accordingly, nitrate
      consumption was reduced from 14.7 capsules per week to 4.0 and 3.8 with
      amlodipine and felodipine, respectively (p = 0.40 between treatments, and p <
      0.001 compared with baseline). Adverse reactions were infrequent and distributed
      similarly between the two treatments. It is concluded that both drugs effectively
      reduced ischemic episodes and anginal attacks and were well tolerated in patients
      with stable angina pectoris. There was no evidence that the two regimens were
      different in their antiischemic and antianginal properties.

PMID- 9156364
TI  - Relaxant actions of nonprostanoid prostacyclin mimetics on human pulmonary
      artery.
AB  - The specific prostacyclin (IP) receptor agonist cicaprost relaxed human pulmonary
      artery preparations precontracted with phenylephrine [50% inhibitory
      concentration (IC50) approximately 0.6 nM], U-46619 (IC50 approximately 0.9 nM),
      and K+ (approximately 40% maximal relaxation); endothelium removal had little
      effect on relaxant activity. Ranking of relaxant potencies for prostacyclin and
      five of its analogs was 17 alpha, 20-dimethyl-delta 6,6a-6a-carba PGI1 (TEI-9063)
      > or = cicaprost > iloprost > prostacyclin > taprostene > benzodioxane
      prostacyclin > 15-deoxy-16 alpha-hydroxy-16 beta,20-dimethyl-delta 6,6a-6a-carba
      PGI1 (TEI-3356). The potency of the isocarbacyclin TEI-3356 may have been under
      estimated because of its contractile (EP3 receptor agonist) activity. The potency
      ranking of four nonprostanoid prostacyclin mimetics was 3-[4-(4,5-diphenyl-2
      oxazolyl)-5-oxazolyl]phenoxy] acetic acid (BMY 45778; IC50 approximately 2.5 nM)
      > > 2-[3-[2-(4, 5-diphenyl-2-oxazolyl)ethyl]phenoxy]acetic acid (BMY 42393) >
      octimibate > CU 23 (a novel diphenylindole). From IP receptor binding affinities
      obtained on human platelet membranes, it is suggested that the slightly shallower
      log concentration-response curves for BMY 45778, BMY 42393, and CU 23 may reflect
      the near-maximal receptor occupancy required for complete relaxation. A fifth
      nonprostanoid, CU 602, had much shallower log concentration-response curves than
      cicaprost against phenylephrine tone but not against U-46619 tone; this may
      indicate IP receptor partial agonism coupled with TP receptor antagonism. The
      relaxant actions of the nonprostanoid mimetics were more persistent than those of
      the prostacyclin analogs on washout of the organ bath; by the inhalation route,
      this type of compound may be retained within pulmonary tissue and thus afford
      greater pulmonary/systemic selectivity than currently used pulmonary
      vasodilators.

PMID- 9156365
TI  - Tyrosine kinase inhibitor markedly suppresses the development of coronary lesions
      induced by long-term treatment with platelet-derived growth factor in pigs in
      vivo.
AB  - Platelet-derived growth factor (PDGF) plays an important role in the development
      of coronary atherosclerosis. However, it remains to be examined what morphologic
      and functional changes are induced in vivo by the long-term treatment with PDGF
      itself or what pharmacologic interventions could suppress those changes in vivo.
      Our study was designed to address these points. We examined the effects of long
      term treatment with PDGF on the porcine coronary artery in vivo. Under aseptic
      conditions, the proximal segments of the left porcine coronary artery were gently
      wrapped with cotton mesh absorbing sepharose beads either with or without
      recombinant human PDGF-AA or -BB. Two weeks after the operation, coronary
      hyperconstrictions to intracoronary serotonin or histamine were noted at the
      sites treated with PDGF-AA or -BB. Histologically, neointimal formation and
      geometric remodeling (reduction of the total vessel area) were noted at the PDGF
      treated sites. These functional and histologic changes of the coronary artery
      induced by PDGF were markedly inhibited by cotreatment with ST 638, a specific
      inhibitor of tyrosine kinases. A Western blot analysis showed that ST 638
      markedly suppressed the PDGF-induced tyrosine phosphorylations in the coronary
      segment. These results indicate that long-term treatment with PDGF induces
      neointimal formation, geometric remodeling, and vasospastic responses in vivo,
      for all of which, activation of tyrosine kinases is substantially involved.

PMID- 9156366
TI  - Role of nitric oxide in substance P-induced vasodilation differs between the
      coronary and forearm circulation in humans.
AB  - It has been shown that substance P causes endothelium-dependent vasodilation in
      the human coronary and forearm vessels. However, the precise mechanism whereby
      substance P dilates the coronary and peripheral vasculatures is unknown in
      humans. The aim of this study was to examine whether the vasodilator effect of
      substance P is mediated by nitric oxide in the human coronary and forearm
      vessels. Eight patients with normal coronary angiograms were studied for the
      measurements of coronary blood flow (intracoronary Doppler guide wire and
      quantitative coronary arteriography) and forearm blood flow (strain-gauge
      plethysmograph). Intracoronary acetylcholine (10 micrograms/min for 2 min) and
      substance P (30 and 90 ng/min for 2 min) increased coronary blood flow from the
      baseline value. Intracoronary infusion of NG-monomethyl-L-arginine (L-NMMA) at
      200 mumol significantly attenuated the magnitudes of increase in coronary blood
      flow induced by both acetylcholine (p < 0.01) and substance P (p < 0.01).
      Acetylcholine (4, 8, and 16 micrograms/min for 2 min) and substance P (0.8, 1.6,
      and 3.2 ng/min for 2 min) also increased forearm blood flow in a dose-dependent
      manner. Intraarterial L-NMMA (8 mumol/min for 5 min) decreased the magnitudes of
      increase in forearm blood flow induced by acetylcholine (p < 0.01). L-NMMA at the
      same dosage decreased the increase in forearm blood flow induced by substance P,
      but the magnitude of the inhibitory effect of L-NMMA on blood-flow responses to
      substance P was significantly smaller in the forearm than in coronary vessels. It
      is suggested that endothelium-derived nitric oxide contributes to substance P
      induced vasodilation, and that the contribution of nitric oxide to substance P
      induced vasodilation is smaller in the forearm than in coronary circulation.

PMID- 9156368
TI  - Selecting and validating biologic markers for drug development.
AB  - Biochemical and clinical markers are critical for efficient development of new
      molecular entities. Biologic markers of drug effect, sometimes referred to as
      "surrogate" markers, are used when such clinical outcome measures as survival are
      substantially delayed relative to predictive biochemical changes or clinical
      effects of the new molecular entity. Biologic markers have generally been used
      for early-phase decision-making studies and accelerated regulatory approvals for
      much-needed drugs to treat cancer and acquired immune deficiency syndrome (AIDS).
      The rationale for these two uses of biologic markers is different and therefore
      the foundation required for establishing and validating each may be different.
      The theoretical foundation required for a marker that will be used to justify the
      regulatory approval of a treatment for a life-threatening disease should be
      greater than the required for an early decision-making study with an angiotensin
      II antagonist that will be used to treat mild to moderate hypertension. Use of
      CD4 counts as "surrogate markers" for prolonged survival was inappropriate. In
      contrast, changes in angiotensin-II concentrations and other renin-angiotensin
      system biochemical markers, observed for the first time in a study in humans,
      with a purported angiotensin-II receptor antagonist indicate that the new
      molecular entity is working as hoped. This is a good decision-making tool,
      because theory indicates that these changes should lead to reduced blood
      pressure, which is a predictive "surrogate" for reduction in subsequent
      cardiovascular events. Surrogate, biologic markers should be used only if they
      have a rational theoretical basis, are proven in preclinical or clinical
      experience, and are measured with validated methods. Different validation
      acceptance criteria for decision-making markers compared with markers used for
      regulatory approval must be prospectively acknowledged and delineated.

PMID- 9156367
TI  - The role of nitric oxide in modulating ischaemia-induced arrhythmias in rats.
AB  - The effect of a nitric oxide (NO) donor and the influence of endogenous NO in
      modulating ischaemia-induced arrhythmias was assessed in anaesthetised rats. The
      nitric oxide donor C87-3754 (1 mg/kg) caused a significant reduction in arterial
      blood pressure before coronary artery ligation but did not influence the
      incidence or severity of ventricular arrhythmias during a 30-min period of
      myocardial ischaemia [60 and 58% incidence of ventricular fibrillation (VF) in
      control and treated rats, respectively]. When the hearts were preconditioned by a
      short (3 min) coronary artery occlusion before the 30-min period of ischaemia,
      there was a marked reduction in both the number of ventricular ectopic beats (260
      +/- 65 vs. 812 +/- 256 beats/min in controls; p < 0.05) and the incidence of
      ventricular fibrillation (9 vs. 67% in controls; p < 0.05). Neither NG-nitro-L
      arginine methyl ester (L-NAME; 10-100 mg/kg) nor methylene blue (1-50 mg/kg)
      attenuated this marked antiarrhythmic effect of preconditioning. L-NAME caused a
      significant increase in blood pressure with all doses used, whereas methylene
      blue did not increase blood pressure. Both L-NAME and methylene blue attenuated
      ventricular arrhythmias in non-preconditioned hearts. L-NAME reduced the number
      of ventricular ectopic beats (from 812 +/- 256 to 318 +/- 81 beats/min at 10
      mg/kg; p < 0.05), whereas methylene blue decreased the incidence of VF from 67 to
      20% at a dose of 50 mg/kg (p < 0.05). These findings suggest that neither
      endogenous nor exogenously administered NO reduces ischaemic arrhythmias in
      anaesthetised rats. Furthermore, the antiarrhythmic effect of preconditioning in
      this species appears to be independent of NO. The antiarrhythmic effects seen
      with both methylene blue and L-NAME may be the result of actions other than
      inhibition of the production or actions of NO.

PMID- 9156369
TI  - New dimensions in the pharmacologic treatment of schizophrenia and related
      psychoses.
AB  - During the past 5 years unprecedented advances have taken place in the
      psychopharmacology of schizophrenia and related psychoses. Clozapine and
      risperidone, two prototypic novel antipsychotic drugs, have had a significant
      impact on the treatment of psychotic disorders. Additionally, they have ushered
      in another generation of antipsychotic drugs with complex pharmacologic profiles,
      potentially enhanced efficacy, and more benign side-effect profiles than
      previously associated with conventional antipsychotic medications. This review
      highlights these developments, implications for the management of psychotic
      disorders, and the use of novel antipsychotic drugs in specific clinical
      subgroups.

PMID- 9156370
TI  - Using student feedback on examination questions to promote fairness, item
      validity, and learning.
AB  - Ten years' experience with a system of modifying the scoring of examinations in
      pharmacology based on feedback comments from students on individual questions are
      analyzed. Each examination (3 per year for 10 years), approximately 100 items in
      length, was subjected to rigorous editing by a faculty committee and an
      independent reviewer. Putatively correct answers were posted after the
      examination, and students submitted comments anonymously on questions they
      thought justified alternative answers. Those comments accepted as valid by
      faculty were used to modify final scoring. A mean of 7.17 +/- 0.85 questions per
      examination (+/-SE) had valid alternative answers (range, 2-17 questions; median,
      6-7 questions; n = 30 examinations). No examination escaped with fewer than two
      items that had alternative answers accepted in response to students' comments.
      The mean number of deleted items was 1.63 +/- 0.34 (range, 0-6). This feedback
      comments system has received consistently high praise from students who say that
      it improves fairness and validity in examinations. It was now been adopted for
      use in objective examinations in the major courses in this school of medicine.

PMID- 9156371
TI  - Evaluation of the diurnal variation in the pharmacokinetics of zileuton in
      healthy volunteers.
AB  - The diurnal variation in the pharmacokinetic parameters of zileuton were
      evaluated in 12 healthy male volunteers in a three-period study. Periods I and II
      constituted a balanced, randomized, crossover study in which a participant
      received a single dose of 600-mg zileuton either at 7 AM or 11 PM. In period III
      all participants received 600-mg doses four times daily for 5 days. The
      differences between the pharmacokinetics of single doses of zileuton administered
      at 7 AM and 11 PM were not statistically significant. Plasma concentration-time
      profiles of zileuton during the four daily dose intervals at steady state were
      also similar. Values for the pharmacokinetic parameters of zileuton after
      multiple doses were similar to those after single doses, with a minimal
      accumulation of the drug after multiple doses. Overall, there was little or no
      diurnal variation in the pharmacokinetic parameters of zileuton after single and
      multiple doses.

PMID- 9156372
TI  - Pharmacokinetics of zileuton and its metabolites in patients with renal
      impairment.
AB  - The pharmacokinetics of zileuton and its conjugated metabolites were evaluated in
      patients with chronic renal impairment. Five healthy volunteers (creatinine
      clearance > 90 mL/min), five patients with renal failure requiring hemodialysis,
      six with mild (creatinine clearance, 60-90 mL/min), eight with moderate
      (creatinine clearance, 30-59 mL/min), and six with severe (creatinine clearance <
      30 mL/min) renal impairment participated in the study. Zileuton was well
      tolerated by all participants including those with severe renal impairment and
      those receiving hemodialysis. The pharmacokinetics of zileuton were similar in
      healthy volunteers; in patients with mild, moderate and severe renal impairment;
      and in patients with renal failure requiring hemodialysis. The mean
      metabolite/parent-area ratios for the pharmacologically inactive zileuton
      glucuronides progressively increased with the decline in renal function. A very
      small percentage of the administered zileuton dose (< 0.5%) was removed by
      hemodialysis. Therefore, adjustment in the dose regimen of zileuton does not
      appear to be necessary for patients with various degrees of renal impairment and
      patients with renal failure requiring hemodialysis.

PMID- 9156373
TI  - Pharmacokinetics of sirolimus in stable renal transplant patients after multiple
      oral dose administration.
AB  - In this 2-week, ascending dose study, the pharmacokinetic activity of sirolimus
      was examined in 40 stable renal transplant patients treated with cyclosporine and
      prednisone. Nine dose levels (range, 0.5-6.5 mg/m2/12 hr) of sirolimus were
      studied in a parallel design. Mean values for the pharmacokinetic parameters of
      sirolimus calculated in all dose groups were as follows: time to peak blood
      concentration, 1.4 +/- 1.2 hours; terminal half-life, 62 +/- 16 hours; oral dose
      clearance, 208 +/- 95 mL/h/kg; apparent oral steady-state volume of distribution,
      12 +/- 5 L/kg; and blood/plasma ratio, 38 +/- 13. The intersubject variabilities
      in dose clearance, steady-state volume of distribution, and blood/plasma ratio
      were 4.5-fold. Preliminary assessments suggests linear dose proportionality. An
      excellent correlation existed between area under the concentration-time curve and
      trough blood concentration at steady state. Sirolimus did not produce any
      significant changes in area under the concentration-time curve of cyclosporine.
      Preliminary analysis suggested that values for the pharmacokinetic parameters of
      sirolimus vary among races (black versus nonblack) but not among genders.

PMID- 9156374
TI  - Pharmacokinetics of dichloroacetate in adult patients with lactic acidosis.
AB  - The pharmacokinetic properties of the lactate-lowering drug dichloroacetate were
      investigated in 111 adult patients with lactic acidosis who were randomized to
      receive dichloroacetate as part of a placebo-controlled clinical trial. The
      clinical symptoms and etiology of lactic acidosis varied markedly among patients.
      Dichloroacetate, at a dose of 50 mg per kilogram of body weight, was administered
      in a 30-minute intravenous infusion into a peripheral vein. A second dose,
      identical to the first, was administered 2 hours after beginning the first
      infusion. Plasma levels of dichloroacetate were determined from blood samples
      collected periodically up to 288 hours after administration and the data were
      subjected to pharmacokinetic modeling. The pharmacokinetic properties of
      dichloroacetate in these acutely ill patients were complex and differed markedly
      from those in healthy volunteers, whose data fitted a one-compartment
      pharmacokinetic model. In contrast, the data from patients fitted one-, two-, or
      three-compartment pharmacokinetic models or even none of these, depending on the
      individual. Drug clearance in plasma tended to decrease as the number of
      compartments required to fit the data increased or as the number of drug
      treatments increased.

PMID- 9156375
TI  - Pharmacokinetics of nicotine tartrate after single-dose liquid enema, oral, and
      intravenous administration.
AB  - Ulcerative colitis is predominantly a disease of nonsmokers, and transdermal
      nicotine is therapeutic but often results in adverse reactions. Colonic
      administration of nicotine tartrate as a liquid enema could decrease systemic
      nicotine absorption and adverse reactions. The purpose of the current study was
      to determine the bioavailability and pharmacokinetic parameters of nicotine after
      administration by hydrophilic liquid enema (acidic and basic), hydrophobic liquid
      enema (acidic and basic), and by oral and intravenous routes. Thirty healthy
      volunteers received 45 micrograms nicotine base/kg (as nicotine tartrate) in one
      of five formulations (each n = 6): hydrophilic acidic liquid enema, hydrophilic
      basic liquid enema, hydrophobic acidic liquid enema, hydrophobic basic liquid
      enema, and oral solution. All participants also received 15 micrograms nicotine
      base/kg (as nicotine tartrate) intravenously during a separate study period.
      Serum concentrations of nicotine were determined by gas chromatography with mass
      spectrometry. The mean (+/-SD) bioavailabilities of nicotine after administration
      in the liquid enema formulations (hydrophilic acidic 17 +/- 18%, hydrophilic
      basic 16 +/- 16%, hydrophobic acidic 25 +/- 17%, hydrophobic basic 15 +/- 12%)
      were similar to the bioavailability of nicotine after administration by oral
      solution (20 +/- 25%). The bioavailabilities of nicotine for all five
      nonintravenous formulations were significantly less than for intravenous nicotine
      (100%). Serum concentrations of nicotine did not predict adverse reactions.
      Nicotine tartrate administered as either a liquid enema or as an oral solution
      had low bioavailability and was well tolerated. The therapeutic potential of
      nicotine tartrate liquid enemas, which can potentially limit toxicity by local
      (colonic) delivery of high doses of nicotine should be investigated in patients
      with left-sided ulcerative colitis.

PMID- 9156376
TI  - Influence of oral contraceptive use and cigarette smoking, alone and together, on
      antipyrine pharmacokinetics.
AB  - The pharmacokinetics of antipyrine following a single 1-g intravenous dose was
      determined in 63 healthy women. Subjects were divided into 4 groups as follows:
      1) cigarette smokers using low-dose oral contraceptives (n = 15); 2) nonsmokers
      using low-dose oral contraceptives (n = 12); 3) cigarette smokers not using oral
      contraceptives (n = 10); and 4) controls, neither cigarette smokers nor oral
      contraceptive users. Plasma antipyrine concentrations during 24 to 48 hours after
      dosage were measured by high-performance liquid chromatography. Mean kinetic
      variables in the nonsmoking, non-oral contraceptive using control group were:
      volume of distribution, 37.7 L; elimination half-life, 13.2 hours; and clearance,
      34.4 mL/min. In cigarette smoking, non-oral contraceptive users versus controls,
      elimination half-life was reduced (8.0 vs. 13.2 hours, P < 0.05) and clearance
      increased (56.0 vs. 34.4 mL/min, P < 0.05). In nonsmoker oral contraceptive
      users, the reverse was true (elimination half-life was significantly increased:
      16.6 vs. 13.2 hours, P < 0.05; and clearance was significantly decreased: 24.8
      vs. 34.4 mL/min, P < 0.05). In smokers who were using oral contraceptives, values
      were not significantly different from controls (elimination half-life, 11.2
      hours; clearance, 39.5 mL/min). Volume of distribution did not differ among the
      four groups. Thus the opposing effects on antipyrine clearance of the induction
      of metabolism by cigarette smoking and the inhibition due to low dose oral
      contraceptive use in effect negate each other when combined in humans.

PMID- 9156377
TI  - Effect of valproate on the pharmacokinetics and pharmacodynamics of lorazepam.
AB  - The pharmacokinetic-pharmacodynamic interaction between valproate and lorazepam
      was evaluated in this randomized, double-blind, placebo-controlled crossover
      study. Sixteen healthy male volunteers enrolled in the study to receive either
      divalproex sodium (500 mg every 12 hours) or matching placebo for 12 days in the
      first period, and then to receive the other regimen for an identical second 12
      day period. In both periods, lorazepam (1 mg every 12 hours) was administered on
      days 6 through 9 and on the morning of day 10. Concomitant administration of
      divalproex sodium with lorazepam resulted in an 8%, 20%, and 31% increase in
      steady-state maximum plasma concentration, area under the concentration-time
      curve, and trough plasma concentrations of lorazepam, respectively. The apparent
      clearance of lorazepam through the formation of lorazepam glucuronide was reduced
      by 31% during coadministration of divalproex sodium. Pharmacokinetic properties
      of valproate did not change significantly in the ten available participants
      during coadministration of lorazepam. Sedation scales revealed no statistically
      significant differences in sedation between the two regimens. It is concluded
      that valproate increases plasma concentrations and reduces clearance of
      lorazepam, most likely by impairing hepatic glucuronidation, and that
      coadministration of lorazepam does not affect the steady-state pharmacokinetic
      properties of valproate.

PMID- 9156378
TI  - The prospects of treatment failure in the chemotherapy of infectious diseases in
      the 1990s.

PMID- 9156379
TI  - Antibiotic-resistant pneumococci in pediatric disease.
AB  - The surveillance of pneumococcal resistance in nasopharyngeal isolates is a
      practical way to determine the prevalence of resistant strains and is a
      reasonable predictor of resistance in systemic isolates. The increasing
      prevalence of resistance is shifting the distribution of invasive pneumococcal
      serotypes toward those included in conjugate vaccines. If these vaccines reduce
      carriage, they may eliminate or greatly reduce the prevalence of resistant
      strains. Meningitis is the most important infection caused by PRP for which
      penicillin or ampicillin therapy is inappropriate. Although the extended spectrum
      cephalosporins will be effective for most cases of PRP meningitis, it is clear
      that such therapy is not foolproof. It is important for the laboratory to test
      CSF isolates not only for penicillin resistance but also for resistance to the
      cephalosporins. beta-Lactam antibiotics can still be considered appropriate
      empiric therapy for otitis media, pneumonia, or sepsis. However, occasional
      treatment failures with these agents may necessitate use of alternative
      therapeutic strategies.

PMID- 9156380
TI  - Penicillin-resistant pneumococci in adult disease with special reference to AIDS
      patients.

PMID- 9156381
TI  - Genetics and molecular biology of beta-lactam-resistant pneumococci.
AB  - Penicillin-resistant pneumococci have been reported with increasing frequency in
      recent years. Isolates with high-level resistance are now found in many
      countries, and in some countries they constitute a substantial proportion of all
      isolates. A worrying development is the recent emergence of pneumococci with high
      level resistance to third-generation cephalosporins. Resistance to beta-lactam
      antibiotics in pneumococci is due entirely to the development of altered forms of
      the high-molecular-weight penicillin-binding proteins (PBPs) that have decreased
      affinity for the antibiotics. High-level resistance to third-generation
      cephalosporins has occurred by the development of altered forms of PBP1a and 2x,
      whereas high-level penicillin resistance additionally requires alterations of
      PBP2b. Altered PBPs are encoded by mosaic genes that have emerged by
      recombinational events between the pbp genes of pneumococci and their homologs in
      closely related streptococcal species. Horizontal gene transfer, presumably
      mediated by genetic transformation, has also resulted in the dissemination of
      altered pbp genes, and possibly capsular biosynthetic genes, between different
      pneumococcal lineages to produce new resistant clones.

PMID- 9156383
TI  - New prospects for antibacterial agents against multidrug-resistant pneumococci.
AB  - Since the first description of penicillin-resistant pneumococci nearly 30 years
      ago, drug-resistance has become widespread throughout the world. This review
      focuses upon the in vitro susceptibility of penicillin-susceptible and -resistant
      pneumococci to new and existing agents.

PMID- 9156382
TI  - Relatedness among penicillin-binding protein 2b genes of Streptococcus mitis,
      Streptococcus oralis, and Streptococcus pneumoniae.
AB  - Penicillin-binding protein (PBP) 2b similarities among Streptococcus mitis, S.
      oralis, and S. pneumoniae using DNA fingerprinting and sequencing were
      investigated. The polymerase chain reaction (PCR) was performed on 41 penicillin
      susceptible and -resistant clinical isolates of S. mitis and S. oralis using the
      susceptible S. pneumoniae R6 PBP 2b primers. PCR products were then analyzed
      using Hinf I and Sty I restriction enzymes. Of 41 S. mitis/S. oralis isolates
      studied 15 strains produced a PCR product of a similar size to that of S.
      pneumoniae R6. On fingerprinting these 15 strains, 11 different patterns were
      seen using Sty I restriction enzyme and 12 different patterns with Hinf I. The
      PBP 2b genes of the S. mitis and S. oralis isolates studied were found to be very
      heterogenous. The PBP 2b genes of two S. mitis isolates, MICs 0.5 and 2
      micrograms/ml, were sequenced. These PBP 2b genes were found to possess a mosaic
      structure when compared to those of other S. pneumoniae and viridans
      streptococcal species. Analysis of these mosaic blocks indicates that both S.
      mitis strains contain areas that originated from S. pneumoniae as well as regions
      of unknown origin. PBP 2b sequence comparisons of a susceptible S. oralis with
      reported sequences of S. pneumoniae R6 and S. mitis NCTC 10712 revealed what
      appears at this stage to be nucleotide regions unique to S. oralis. A penicillin
      resistant S. oralis strain contained a pneumococcal region of 272 bp that was
      flanked by S. oralis sequences. These specific S. oralis regions have been
      located in PBP 2b genes of penicillin-resistant S. oralis and S. pneumoniae
      isolates described from Europe and South Africa.

PMID- 9156384
TI  - Pneumococcal conjugate vaccines: review and update.

PMID- 9156385
TI  - Antibiotic susceptibility of Streptococcus pneumoniae isolates in Portugal. A
      multicenter study between 1989 and 1993.
AB  - A total of 1,104 strains of Streptococcus pneumoniae were isolated from
      hospitalized patients (75.5%) and from colonization sites at the Public Health
      Institute (24.5%) during the last 4 years (1989-1993). Penicillin resistance
      (defined as MIC > or = 0.1 microgram/liter) was found to increase in time: 4.6%
      in 1989, 4.9% in 1990, 6.4% in 1991, 11.3% in 1992, and 17% in 1993. In 1992,
      0.8% of the strains had penicillin MIC = 2 mg/liter. Increase in penicillin
      resistance was also evident among invasive strains [blood, cerebrospinal fluid
      (CSF), pleura]: 2/92 isolates from 1989-1992 (2.3%) were penicillin resistant as
      compared to 7/101 isolates from 1992 (6.9%). Multiresistance (resistance to three
      or more antibiotics) was 4.4% with penicillin, tetracycline, chloramphenicol
      being the predominant resistant phenotype at the end of 1992. In 1993, strains
      with resistance to penicillin plus chloramphenicol plus tetracycline increased
      further. Erythromycin resistance was usually associated with clindamycin
      resistance, but the majority of such strains remained susceptible to penicillin.
      Drift in the direction of increasing MIC values was also noted during this 3-year
      period among "susceptible" isolates: bacteria with MIC of 6-10 ng/ml representing
      the majority of isolates in 1990-1991 decreased and were replaced by cells with
      MIC of 20 ng/ml. The most frequent pneumococcal serotypes were 23, 19, 3, 6, 14,
      9, and 8, with the frequency of type 9 increasing from 2.9% (in 1989) through
      3.2% (1990) to 6.4% (1992). Among all antibiotic resistant strains, the prevalent
      serotypes were 23, 9, 14, and 6. The chromosomal backgrounds of resistant
      isolates tested by pulsed-field gel electrophoresis showed close resemblance to
      the background of the serotype 23F multiresistant clone first identified in
      Spain. The data suggest that the recent large increase in the frequency of
      penicillin-resistant pneumococci represents the import of this clone into
      Portugal during the early 1990s. The increased frequency of drug-resistant
      pneumococci highlights the importance of continued surveillance of these
      dangerous pathogens.

PMID- 9156386
TI  - Novel penicillin-resistant clones of Streptococcus pneumoniae in the Czech
      Republic and in Slovakia.
AB  - Seventy-two penicillin-resistant Streptococcus pneumoniae isolates collected from
      clinical specimens in the Czech and Slovakian Republics between 1990 and 1992
      were analyzed by a variety of molecular techniques. Most of the highly resistant
      isolates (40/72) (penicillin MIC between 1 up to 16 micrograms/ml) were
      represented by two distinct pneumococcal clones, and most of these isolates
      (35/40) were also resistant to at least two other antibiotics (tetracycline plus
      chloramphenicol or erythromycin). All 17 isolates belonging to the first clone
      were of serotype 14, had very high penicillin MICs (8-12 micrograms/ml), shared a
      common, abnormal penicillin-binding protein (PBP) pattern and one of two related
      pulsed-field gel electrophoretic (PFGE) patterns. The 15 isolates belonging to
      the second clone were all of serotype 19A, had penicillin MICs between 1 and 4
      micrograms/ml, shared a unique, abnormal PBP pattern, and could be divided into
      two subgroups on the basis of PFGE patterns, one of which was indistinguishable
      from the PFGE pattern of a multiresistant capsular type 19A clone of S.
      pneumoniae already identified earlier in Hungary. Thirty-two of the 72
      pneumococcal isolates had lower penicillin MICs (0.1-0.5 microgram/ml), and these
      isolates differed from the more highly resistant ones in several respects: They
      belonged to seven different serotypes, showed large variation in PFGE patterns
      (20 patterns in 32 isolates) and most of them (21/32) were resistant to
      penicillin only. Tentative explanations for these findings, in terms of
      epidemiological and molecular mechanisms, are considered.

PMID- 9156387
TI  - Clinical isolates and nasopharyngeal carriage of antibiotic-resistant
      Streptococcus pneumoniae in Hospital for Infectious Diseases, Sofia, Bulgaria,
      1991-1993.
AB  - The antimicrobial resistance of Streptococcus pneumoniae was surveyed in 1991
      1993 at the Hospital for Infectious Diseases in Sofia, Bulgaria. Pneumococcal
      isolates were collected from routine clinical specimens and from nasopharyngeal
      secretions of inpatient carriers. The incidence of penicillin-resistant S.
      pneumoniae (PRSP) was 24.3% among clinical samples and nasopharyngeal carriage of
      PRSP was as high as 40% among children. Penicillin-resistant strains were more
      frequently resistant to non-beta-lactam antibiotics than were penicillin
      sensitive strains. More than half of the PRSP strains were multiply resistant. On
      the basis of MIC values of ampicillin, it was established that ampicillin was not
      superior to penicillin. The MICs of five cephalosporins were found to increase in
      parallel with the MICs of penicillin G. Some of the pneumococcal strains that
      were highly penicillin-resistant were also resistant to cefotaxime/ceftriaxone
      (MIC = 1-4 micrograms/ml), but the number of strains was small. On the basis of
      MIC values of cefotaxime and ceftriaxone for strains from cerebrospinal fluid,
      both antibiotics may be suitable alternatives for treating meningitis due to
      strains with resistance to penicillin.

PMID- 9156388
TI  - In vitro development of resistance of Streptococcus pneumoniae to beta-lactam
      antibiotics.
AB  - In recent years, increasing numbers of Streptococcus pneumoniae strains
      displaying relative resistance to penicillin have been reported. Epidemiological
      studies have shown a correlation between aminopenicillin administration and
      resistance. We investigated the development of resistance in six strains (four
      sensitive and two intermediate-resistant to penicillin) by serial daily passages
      in subinhibitory concentrations of amoxicillin (AMX), amoxicillin + clavulanic
      acid (AMC), imipenem (IMP), cefixime (CFM), cefatrizine (CTZ), cefadroxil (CDX),
      and cefuroxime (CXM). MICs were determined by the macrodilution method in brain
      heart broth for each daily passage. The number of daily passages needed to
      increase the MIC by a factor of 8 was achieved with AMX, AMC, and CFM for most of
      the strains after a mean of 24, 20, and 11 passages, respectively, and for one
      third of the strains, with CDX, IMP, and CTZ after 11, 11, and 21 passages,
      respectively. Decreased susceptibility to breakpoints for intermediate-resistant
      S. pneumoniae populations was noted for all strains with CFM, AMX, and AMC after
      a mean of 10, 18, and 21 serial passages, respectively, and for four of five
      strains with IMP and CTZ after 12 and 13 passages. CTZ-, CDX-, and CXM-passaged
      variants had increased MIC values only for cephalosporins, while AMX-, AMC-, IMP
      , and CFM-passaged variants exhibited increased MICs to all antibiotics tested.
      These in vitro data appear to be in agreement with epidemiological studies and
      warrant further exploration with respect to possible clinical implications.

PMID- 9156389
TI  - Vancomycin-resistant Enterococcus faecium shunt infection in an infant: an
      antibiotic cure.

PMID- 9156390
TI  - Infectious complications of immunosuppressive therapy in patients with rheumatic
      diseases.
AB  - Infection continues to be a significant cause of morbidity and mortality in
      patients with rheumatic diseases, and, consequently, early diagnosis and
      treatment of infection is critical to the successful medical management of these
      patients. The intensity of immunosuppressive therapy is the dominant risk factor
      for infection in this patient population. Because the manifestations of infection
      in patients with rheumatic diseases are highly variable, the clinician must
      always be vigilant about the possibility of infection even if the clinical
      presentation is highly suggestive of an exacerbation of the underlying disease.
      We have stressed a systematic and individualized approach in the diagnostic
      evaluation of suspected infection in these patients. The first part of the
      evaluation involves forming a list of the most likely pathogens based on a
      detailed history and physical examination and the intensity and type of
      immunosuppressive therapy the patient is receiving. The physician must then
      formulate a plan designed to establish a diagnosis expeditiously and with the
      least morbidity.

PMID- 9156391
TI  - Septic arthritis.
AB  - Septic arthritis is a medical emergency that can lead to significant morbidity
      and mortality. Prompt recognition and treatment are critical to ensuring a good
      prognosis. Thus, this article reviews the clinical presentation, microbiology,
      diagnostic workup, and outcome of nonprosthetic joint infections.

PMID- 9156392
TI  - Prophylactic use of antibiotics and vaccines in patients with rheumatologic
      disorders.
AB  - In patients with serious underlying medical conditions, preventive interventions
      are a prudent, cost-effective, but underused strategy that could lessen morbidity
      and even mortality. In particular, immunization status should be assessed in all
      patients with rheumatologic disorders. Tuberculin reactivity is optimally
      documented before initiation of steroid therapy. It is often easier (and wiser)
      to prevent an infection than to treat it in a compromised host.

PMID- 9156394
TI  - Cerebrovascular complications of rheumatic disease.
AB  - Cerebral ischemia and infarction, intracerebral hemorrhage, subarachnoid
      hemorrhage, cerebral venous thrombosis, and cerebral vasculitis are dreaded but
      largely uncommon complications of most rheumatic diseases. In some conditions,
      however, such as the antiphospholipid syndrome or Behcet's disease, stroke may be
      the presenting complaint. A format for approaching the patient and localizing the
      cerebrovascular lesion has been presented along with a summary of the specific
      rheumatologic diseases implicated for each stroke subtype.

PMID- 9156393
TI  - Evaluation and treatment of respiratory failure in neuromuscular disease.
AB  - Respiratory failure is a relatively uncommon feature of most neuromuscular
      disease. It accounts for most of the morbidity and mortality associated with
      these disorders, however. In most cases, aggressive supportive care, specific
      immunologic treatment, and treatment of associated medical conditions result in
      improvement in respiratory function and a favorable outcome.

PMID- 9156395
TI  - The surgical management of patients with rheumatoid cervical spine disease.
AB  - Rheumatoid arthritis is an inflammatory disease that commonly affects the
      cervical spine. This article reviews the incidence of spinal involvement, the
      clinical manifestations of spinal disease, and the types of instability patterns
      that may occur and their radiographic diagnosis. Appropriate guidelines for
      obtaining imaging studies and for surgical referral is also described. Finally,
      the role of surgical stabilization is discussed.

PMID- 9156396
TI  - Inflammatory cardiomyopathy. The controversy of diagnosis and management.
AB  - This article reviews the theories regarding the causes of lymphocytic
      myocarditis, including viral and immunologic (cellular versus humoral) causes.
      Also covered is the relationship of dilated cardiomyopathy to myocarditis, the
      familial predilection for dilated cardiomyopathy in some cases, shortcomings of
      the various modalities for diagnosing lymphocytic myocarditis, and the occurrence
      of lymphocytic myocarditis in association with systemic illnesses. Lastly,
      treatment options for myocarditis are explored.

PMID- 9156397
TI  - Upper airway obstruction in the rheumatic diseases.
AB  - Upper airway obstruction is a potentially life-threatening event that can be
      managed effectively when promptly recognized and treated. For this reason, all
      patients who are suspected of having disease affecting the larynx or trachea
      should be regarded as having a potentially compromised airway until proven
      otherwise. Although clinically significant upper airway diseases occur
      infrequently in rheumatic disorders, these manifestations should be considered in
      such patients who present with upper airway symptomatology.

PMID- 9156398
TI  - Pulmonary hypertension in systemic autoimmune disease.
AB  - Rare in occurrence, insidious in onset, and relentless in its course, pulmonary
      hypertension in systemic autoimmune disease remains one of the most challenging
      entities to diagnose and treat today. The subtlety and nonspecificity of its
      symptoms and signs, the lack of availability of sensitive, noninvasive, accurate
      diagnostic tests, the rudimentary understanding we have of its pathogenesis, the
      multiplicity of findings on histopathologic survey, and the paucity of data from
      large-scale therapeutic trials in this population all pose many frustrations for
      patient and physician. Although supportive, symptomatic therapy remains the
      mainstay of treatment, we continue to await the results of carefully conducted
      clinical trials investigating antiinflammatory drugs and vasodilators. Careful
      scrutiny of the histologic lesions seen in pulmonary hypertension has shown
      striking similarity with the changes of PPH in some patients, and close follow-up
      of patients diagnosed with PPH has shown that some of them later develop evidence
      of a specific autoimmune disease like scleroderma. A natural tendency to
      extrapolate the use of therapeutic modalities of PPH to patients with autoimmune
      disease-associated pulmonary hypertension then results. We are thus encouraged by
      the lessons learned from the past about PPH; studies of patients with PPH have
      identified a subset of them who enjoy a distinct survival advantage with use of
      vasodilators or transplantation. We remain hopeful that future investigations in
      the treatment of autoimmune disease-associated pulmonary hypertension will yield
      similar information, and that we will be able to provide afflicted individuals
      some long-awaited improvements in quality and duration of life.

PMID- 9156399
TI  - Alveolar hemorrhage in patients with rheumatic disease.
AB  - Alveolar hemorrhage is an uncommon event that is associated with several
      underlying disorders, many of which are immunologically mediated. Careful
      evaluation of basic laboratory tests, extrapulmonary physical findings, and
      serology usually leads to the correct diagnosis. Significant overlap, however,
      exists, and pathologic (especially immunopathologic) evaluation of pulmonary or
      renal biopsies may be necessary. An accurate diagnosis is essential because
      treatment is most helpful when directed at the underlying diagnosis. Supportive
      therapy may be needed until the underlying disease is diagnosed and specific
      therapy is initiated.

PMID- 9156400
TI  - Autoimmune coagulation disorders.
AB  - The spontaneous onset of autoantibodies against circulating factors, including
      factors II, V, VII, VIII, IX, XI, XII, and XIII, is a phenomenon of unclear
      causes. It may occur in patients with no underlying disease process or may be
      antedated by autoimmune diseases and malignancies. The antibodies are almost
      always IgG and are most commonly directed at F VIII. They generally present with
      a bleeding diathesis in patients with no history of prior bleeding events. The
      laboratory abnormalities vary depending on whether the inhibitor involves the
      intrinsic or extrinsic pathway of coagulation, and the laboratory studies may
      vary depending on the technique used. Supportive measures are used initially but
      are generally not completely effective. Supportive measures are followed by blood
      products, such as recombinant human F VIII, porcine F VIII, or PCC/aPCC. There
      are limitations to each of these, however. If bleeding is severe and high titers
      of inhibitors are present, plasma-pheresis may lead to a temporary decrease in
      the titer but is short-lived. Immunosuppressive therapy should ultimately be
      attempted to suppress further antibody production. Spontaneous remission may
      occur with some of the inhibitors, primarily postpartum or drug related, for
      reasons not fully understood.

PMID- 9156401
TI  - Hematologic complications of rheumatic disease therapies.
AB  - Hematologic side effects of rheumatic disease therapies are generally mild and
      reversible; however, the clinician must be alert for potential profound and life
      threatening toxicities. A knowledge of the toxicity patterns for the individual
      drugs is necessary to anticipate potential complications. Management of acute
      leukemias and lymphomas arising in patients with connective tissue disorders is
      particularly challenging. Further data are needed to define the best treatment
      options and thus enrollment in clinical trials is encouraged for these patients.

PMID- 9156402
TI  - Emergency and critical care issues in pediatric rheumatology.
AB  - The study of critical care issues in pediatric rheumatology is in its infancy,
      and the available literature is largely case studies and small retrospective
      series. A child's limited communication skills and the lack of understanding of
      disease consequences by both parent and child may cause both overuse and underuse
      of emergency services. To the extent that small case experiences in children with
      rheumatic diseases do not adequately reflect possible disease presentations or
      diagnostic and treatment options, pediatric and adult rheumatologists,
      intensivists, and emergency physicians should readily turn as needed to larger
      reported experiences in adults with similar conditions.

PMID- 9156403
TI  - Thrombotic syndromes and autoimmune diseases.
AB  - Maintenance of blood flow involves the dynamic interactions between the
      endothelium, circulating cellular components, coagulation factors, and factors
      involved in fibrinolysis. Autoantibodies, inflammatory cytokines and other
      undefined triggers in a genetically predisposed person may lead to an imbalance
      in the equilibrium between the various hemostatic pathways resulting in
      potentially catastrophic thrombotic events. This article reviews the clinical
      manifestations and treatment of selected, potentially life-threatening thrombotic
      syndromes that may occur in association with autoimmune diseases. Special mention
      is made of thrombotic events associated with Behcet's syndrome.

PMID- 9156404
TI  - Heterogeneity of unfractionated heparins studied in connection with species,
      source, and production processes.
AB  - The heterogeneity of unfractionated heparins (Hep) can be correlated to the
      species and organs of origin and to the process of production. Heparins,
      extracted by different, validated processes from different organs and/or tissues
      (mucosa, thymus, pancreas, placenta, lung, intestine) or mammals (pig, beef,
      sheep, man) and other vertebrates (chicken), have been examined by HPLC analysis
      of heparinase digests. By analysis of disaccharides many observations have been
      made. Porcine mucosa heparin (pm-Hep) was always found to contain higher amounts
      of the disaccharides delta UA-GlcNS,6S and delta UA-2S-GlcNS,6S, than did bovine
      mucosa heparin (bm-Hep), whereas bm-Hep always showed higher amounts of the
      sequence IdoA(2OSO3)-GlcNSO3 than did pm-Hep. These findings mean that the last
      step of the biosynthesis, the 6-O-sulfation of glucosamine-N-sulfate (GlcNSO3),
      is accomplished; in bm-Hep, to a lesser extent than in pm-Hep. The 6-O-sulfated
      molar fractions of pig mucosa, chicken intestine, beef pancreas, beef placenta,
      and beef lung heparins were higher than the corresponding molar fractions of beef
      mucosa and beef thymus Heps. Also the manufacturing processes can partially
      rearrange the heparin structure. Even 6-O-sulfation enrichment (by
      chromatographic purification) or base-catalyzed displacement of sulfate groups
      from IdoA2SO3 occurred. The resulting anticoagulant activity roughly correlated
      with the percentage of trisulfated disaccharide and the 6-O-sulfated molar
      fraction. The heparin from human placenta was similar to pm-Hep. The observed
      species- and organ-dependent structural characteristics support the suggestion by
      Nader and Dietrich (in Heparin, Chemical and Biological Properties, Lane DA, U
      Lindahl (Eds). Arnold, London, 1989, p 81) on the antipathogenic role of heparin.
      The 6-O-sulfation of glucosamine, present in higher amounts in organs that
      function as barriers against many foreign bodies, like lung, placenta, intestine
      of chicken and pig, may play an important role in this antipathogenic action of
      Hep.

PMID- 9156405
TI  - Heparins, low-molecular-weight heparins, and other glycosaminoglycans analyzed by
      agarose gel electrophoresis and azure A-silver staining.
AB  - A sensitive, nonradioactive azure A-silver staining method combining agarose gel
      electrophoresis was established and evaluated. Unfractionated heparins (UFHs),
      low-molecular-weight heparins (LMWHs), heparan sulfate (HS), chondroitin sulfate
      A (CSA), dermatan sulfate (DS), keratan sulfate (KS), and hyaluronic acid (HA)
      were analyzed. The detection limit of the method was 0.5 ng for heparin, LMWH,
      HA, CSA, and DS, 2 ng for KS, and 6 ng for HA in the 2-microliter sample volume.
      Dilution curves demonstrated linear correlation between the logarithm of the
      concentration of glycosaminoglycans (GAGs) and their optical absorbance at 548
      nm. The linear ranges were 1 to 500 ng/microliter for heparins, LMWHs, HS, DS,
      and CSA, 3 to 500 ng/microliter for KS, and 8 to 500 ng/microliter for HA. GAGs
      have their characteristic migration patterns and their Rf value decreased from
      CSA to KS, DS, HS, heparin, and HA. The differences were described for heparins
      and LMWHs. LMWHs migrated faster and displayed broader bands than unfractionated
      heparins. It was also observed that some unfractionated heparins contained low
      sulfated GAGs as contamination, which seemed to be DS as judged by their
      migration patterns.

PMID- 9156406
TI  - Monoclonal antibodies against heparin and heparinoids.
AB  - The antigenicity of glycosaminoglycans and galactosaminoglycans is very weak.
      Accordingly, only a few reports on the successful production of monoclonal
      antibodies against glycosaminoglycans and galactosaminoglycans have been
      published. Antibodies have been raised against the heparinlike compounds heparan
      sulfate, chondroitin sulfate, and keratan sulfate. The production of heparin
      antibodies was reported. But further analysis showed that the antibodies were not
      directed against native heparin but against heparin conjugates or chemically
      modified heparins. After immunization with a heparin-bovine serum albumin
      conjugate, prepared by reductive amination, a monoclonal antibody against heparin
      and heparin fractions was obtained (Huhle et al: Semin Thromb Hemostas 20:193
      204, 1995). For further analysis, tyramine, which was covalently bound to low
      molecular-mass heparin (LMMH) by endpoint attachment (Malsch et al: Anal Biochem
      217:255-264, 1994), was labeled with iodine-125 at the aryl residue. The tracer
      antibody complex was immunoprecipitated by goat anti-mouse immunoglobulin IgG.
      H1.18 recognized specifically intact heparin and heparin fractions. The lower
      detection limit for heparin preparations was 100 ng/mL. The H1.18 antibody was
      purified by ammonium sulfate precipitation. H1.18 remained biologically and
      functionally active after purification. The smallest disaccharide that was
      detected by H1.18 was found to be iduronic acid-anhydromannose, obtained by
      nitrous acid degradation of LMMH. Endpoint attachment of tyramine to
      anhydromannose did not modify the binding of the disaccharide to H1.18,
      indicating the importance of iduronic acid for binding of glycosaminoglycans to
      the antibody.

PMID- 9156407
TI  - Measurement of fluorescent-labeled LMM-heparin in biological fluids using
      protamine-linked microbeads.
AB  - A quantitative assay for fluorescent heparin in a purified system and in plasma
      was developed (Piazolo et al: Semin Thromb Hemostas 20:227-235, 1994). The
      protamine microbeads (1.6 microns) showed a broad size distribution and a large
      standard variation in low concentrations. Our aim was to optimize these protamine
      microbeads for the measurement of fluorescent heparin. The following results were
      obtained: Paramagnetic protamine microbeads of different average diameters (0.8,
      1.6, 2.8, and 4.5 microns) were synthesized by cyclocarbodiimide and tosyl
      activation. These microbeads bind heparin and are assayed using flow cytometry.
      The protamine concentration on the surface of the beads ranged between 2.0 and 61
      mg/mL. The protamine microbeads bound fluorescent heparin and were analyzed by
      flow cytometry. The protamine microbeads bound LMM-heparin-tyramine-FITC dose
      dependently in saline solution, plasma, and blood. There are substantial
      differences between the microbeads of different origins with regard to the amount
      of protamine bound, the sensitivity of the detection, and the reliability for the
      determination of heparins in plasma and blood. The minimal sensitivity of the
      final method was 0.001 U/mL LMMH-tyramine-FITC in saline solution and in plasma.
      Human blood cells were not bound to protamine microbeads. The half-maximal
      binding of LMMH-tyramine-FITC of the different protamine-coated microbeads ranged
      from 1.7 to 8.0 micrograms/mL in saline solution, 2.3 to 8.7 micrograms/mL in
      plasma, and 3.1 to 6.4 micrograms/mL in blood. We conclude that all protamine
      microbeads can be used to quantify the concentration of LMMH-tyramine. Protamine
      Dynabeads M-450 (diameter 4.5 microns) have advantages over other microbeads
      because of their more homogeneous size distribution, a higher selectivity, and
      they can be measured together with leukocytes. They are currently used to develop
      a competitive binding assay for heparin in plasma.

PMID- 9156408
TI  - Pharmacokinetic properties of LMW-heparin-tyramine fractions with high or low
      affinity to antithrombin III in the rat.
AB  - We have recently presented evidence that a macrophage scavenger receptor-mediated
      pathway is responsible for the hepatic uptake of unfractionated heparins and low
      molecular-weight heparins (LMWHs) in the rat. The same receptor-mediated pathway
      was partially responsible for the removal of oxidized low-density lipoprotein.
      Unfractionated and fractionated LMWHs exert their anticoagulatory effects
      predominately by reversibly binding to the plasma glycoprotein antithrombin III.
      In this study LMWHs modified by endpoint attachment of tyramine were radiolabeled
      and their fractions with low or high affinity to AT-III studied in vivo in rats.
      The high-affinity fraction was predominately cleared from the circulation by a
      hepatic uptake mechanism. About 25% of the injected high-affinity tracer material
      was recovered, whereas only about 8% of the low-affinity material was found in
      the liver after 180 minutes. Blocking the scavenger receptor-mediated liver RES
      uptake mechanism by maleylated bovine serum albumin led to a considerable decline
      in liver uptake (9 versus 25%). The low-affinity material was rapidly eliminated
      into the urine after 180 minutes. About 45% of the low-affinity material was
      excreted versus 23% of the high-affinity material. Tight binding to AT-III
      prevented LMWH-tyramine from being rapidly cleared from the circulation via the
      kidneys into the urine; instead, the scavenger receptor-mediated hepatic uptake
      mechanism seemed to be more dominant in removing material with high affinity to
      AT-III from blood.

PMID- 9156409
TI  - Capillary electrophoresis of r-hirudin and a polyethylene glycol derivative of r
      hirudin (PEG-hirudin).
AB  - Recombinant (r-) hirudins and PEG-hirudin are currently tested for anticoagulant
      therapy. For their concentration measurement, radioimmunoassay and HPLC methods
      are available. The separation of r- and PEG-hirudin is currently performed by
      HPLC. However, the sensitivity of the method is low. Capillary electrophoresis is
      a rapid, selective technique that requires low sample amounts. Our aim was the
      development of a capillary electrophoresis method to measure r- and PEG-hirudin.
      The results are as follows: In a borate solution (0.3% boric acid and 0.4% sodium
      tetraborate, pH 9.5) r-hirudin was separated from PEG-hirudin in a purified
      system using a fused silica capillary (50 cm long and 75-micron i.d. and reversed
      polarity). A neutral capillary with a 20 mM tricine buffer (pH 8.0, field
      strength 500 V/cm) was also effective in resolving r- from PEG-hirudin. A linear
      correlation was found between the peak area and the concentration between 20
      micrograms/mL and 10 mg/mL for hirudin (r2 = 0.99) and between 1.25 and 10 mg/mL
      for PEG-hirudin (r2 = 0.99). In human plasma mixtures, r- and PEG-hirudin were
      completely separated. The linear correlation between the peak area and the
      concentration was r2 = 0.99. CONCLUSION: In a fused silica capillary, r- and PEG
      hirudin are separated in a purified system. Capillary electrophoresis which is
      performed in a neutral capillary, resolves r- from PEG-hirudin in a purified
      system, in plasma and in urine. The sensitivities of the methods are comparable.
      Capillary electrophoresis separates r- from PEG-hirudin and may be applied to
      biologic systems to measure the concentration and purity of r- and PEG-hirudin.

PMID- 9156411
TI  - Prevention of recurrences after deep venous thrombosis: role of low-molecular
      weight heparins.
AB  - The management of deep venous thrombosis (DVT) requires an initial treatment with
      unfractionated (UF) or low-molecular-weight (LMW) heparin followed by oral
      anticoagulants (OA) for at least 3 months. OA therapy, however, requires
      laboratory monitoring and is associated with a definite bleeding risk. Therefore,
      alternative treatments such as UF or LMW heparin have been evaluated. In a study
      by Monreal et al in patients with DVT and contraindications to OA, dalteparin
      (5000 anti-Xa U b.i.d.) was equivalent to UF heparin (10,000 IU b.i.d.) and was
      associated with fewer vertebral fractures. In a study by Pini et al, Enoxaparin
      (4000 anti-Xa U once daily) was evaluated against OA and showed similar efficacy
      with fewer bleeding complications in the 3-month treatment period. A number of
      studies have recently shown that the risk for late thrombotic recurrences for
      patients developing postoperative DVT or associated with other transient risk
      factors is much lower than in patients with idiopathic DVT or associated with a
      persistent risk factor, suggesting that for the formers, 4 to 6 weeks of OA
      therapy may be sufficient. LMW heparins appear to be a promising alternative
      therapy for these patients, because in the first month of OA administration the
      risk for bleeding is higher and the need of laboratory monitoring more stringent.
      This should be evaluated in appropriate clinical trials.

PMID- 9156410
TI  - Tissue factor pathway inhibitor (TFPI) antigen plasma level in patients with
      interstitial lung disease before and after heparin administration.
AB  - The extrinsic pathway is probably the predominant pathway in initiating blood
      coagulation in inflammatory lung diseases. Tissue factor pathway inhibitor (TFPI)
      is a Kunitz-type protease inhibitor of factor VIIa/tissue factor in the presence
      of factor Xa. As it has been shown recently that TFPI plasma levels are increased
      under acute inflammatory conditions, we studied TFPI antigen plasma levels before
      and after injecting 20 IU/kg body weight of unfractionated heparin into 49
      patients with different stages of sarcoidosis, into 9 with idiopathic pulmonary
      fibrosis, and into 15 normal controls. TFPI, before injecting heparin, was
      significantly increased in all sarcoidosis stages (stage I: 97.6 +/- 6.4 ng/mL;
      stage II: 116.2 +/- 11.9 ng/mL; stage III: 116.3 +/- 7.3 ng/mL) and in idiopathic
      pulmonary fibrosis (116.8 +/- 16.1 ng/mL), as compared to the control group (77.7
      +/- 3.3 ng/mL). No correlation was found between the intensity of the activity of
      sarcoidosis, measured as BAL white cell count, and TFPI. Five minutes after
      heparin administration the rise in TFPI was lower, although not statistically
      significant, in all sarcoidosis stages than in controls. In contrast, idiopathic
      pulmonary fibrosis had a similar or even higher TFPI elevation than the control
      group. In sarcoidosis the elevated TFPI and the lower capacity by endothelial
      cells to release TFPI after heparin may represent a compensatory mechanism to
      prevent blood clotting and/or the endothelial cell dysfunction of the
      microvasculature in this condition. In contrast, the extensive mesenchymal cell
      proliferation present in idiopathic pulmonary fibrosis could explain our
      findings, as it has been shown that cultured human mesangial cells produce and
      release TFPI.

PMID- 9156412
TI  - Identification of candidates for prevention of venous thromboembolism.
AB  - The rationale for prophylaxis of venous thromboembolism (VTE) is based on the
      frequently clinically silent nature of the disease. A number of risk factors for
      VTE have been known for a long time, even if some of them are still
      controversial. Many studies have been performed in the surgical field, and have
      established different risk classes for VTE. Such risk stratification is
      especially determined by type of surgery and to some extent by personal
      characteristics of patients, and it defines operations at high, intermediate, and
      low risk for VTE. According to this classification, prophylaxis of VTE is
      mandatory in some cases, less useful in others. Less information is available on
      medical diseases, in which the clinical conditions and the intrinsic
      characteristics of patients determine the class of risk for VTE. Different
      strategies for identifying patients who should undergo prophylaxis have been
      proposed based on risk factor evaluation in the individual patient. However, even
      if such an approach may be of help for the physician, its validity is still
      impaired by the difficulty of taking into account all of the variables possibly
      involved in VTE occurrence.

PMID- 9156413
TI  - Heparin in patients with venous thromboembolism and contraindications to oral
      anticoagulant therapy.
AB  - After an initial course of heparin therapy, patients with venous thromboembolism
      require continuing anticoagulant therapy for several months after hospital
      discharge to prevent recurrences. For most patients oral anticoagulants are the
      treatment of choice. However, patients receiving therapy need to participate in
      frequent and careful laboratory monitoring, and a patient's inability or
      unwillingness to cooperate in such procedures should contraindicate the use of
      oral anticoagulants. Oral anticoagulants may also be contraindicated in patients
      with serious coexisting conditions. Finally, several authors consider the oral
      anticoagulants should not be administered to elderly people, and when
      administered to pregnant women, they may be associated with embryopathy. Several
      trials have demonstrated that subcutaneous heparin may be an acceptable
      alternative to coumarin. However, the high doses required for continuing
      prophylaxis have raised concerns about the risks of development of osteoporosis
      and bone fractures. The recently developed low-molecular-weight heparins
      constitute a good alternative.

PMID- 9156414
TI  - Low-molecular-weight heparin for the out-of-hospital treatment of venous
      thrombosis: rationale and clinical results.
AB  - LMWH preparations have been proven to be safe and effective in the outpatient
      management of acute DVT. Although LMWHs are more expensive than unfractionated
      heparin, the lack of need for laboratory monitoring of LMWHs and their potential
      for outpatient treatment more than offset the drug-related cost difference and
      result in a net cost savings in favor of LMWHs. LMWHs have undergone limited
      investigation for the secondary prevention of venous thromboembolism after an
      initial inpatient course of unfractionated haparin. To date, LMWHs have been
      given in prophylactic doses in these trials. In this setting, the LMWHs are
      associated with a similar risk for bleeding as fixed, intermediate-dose
      unfractionated heparin in patients with a high risk for bleeding. In patients
      with no increase in bleeding risk, fixed prophylactic-dose LMWH appears to be
      associated with both a lower risk for bleeding than warfarin (target INR of 2.0
      to 3.0) and an increased risk for recurrence, although these findings need to be
      confirmed in larger trials.

PMID- 9156415
TI  - Dosage, anticoagulant, and antithrombotic effects of heparin and low-molecular
      weight heparin in the treatment of deep vein thrombosis.
AB  - We have performed a prospective, randomized, controlled trial comparing
      continuous intravenous unfractionated heparin with twice-daily subcutaneous
      (s.c.) high-dose low-molecular-weight (LMW) heparin in the initial treatment of
      50 patients with acute proximal deep vein thrombosis. In this article we analyze
      the relationship between the dosage of the heparins, the anticoagulant effects on
      aPTT, and thrombin and factor Xa inhibition to the improvement of the Marder
      score after a 10-day treatment period. Improvement of the Marder score was
      observed in about 70% of patients without regard to administration of
      unfractionated or LMW heparin. Patients in both treatment categories were divided
      into two groups, namely, those who showed an improvement of the Marder score and
      those who did not. In the group of patients with unfractionated heparin and
      regression of thrombus size the mean dosage was 33,000 U/day, whereas the mean
      dosage was 37,000 U/day in the patients with status idem of the Marder score
      after the 10-day treatment period. Thrombin clotting time values were in contrast
      to the dosage. Patients with regression of thrombosis showed higher thrombin
      clotting time values compared with those with status idem. These results were
      also seen with aPTT and the Heptest coagulation assay, but the differences
      between the two groups were less pronounced. No differences between these two
      groups of patients were seen or detected with the S2222 chromogenic anti-factor
      Xa method. Patients receiving 2 x 12,000 IU s.c./day LMW heparin did not show
      these differences, the dosage being adjusted by the anti-Xa levels, ranging from
      0.6 to 1.0 U/mL 4 hours after the s.c. injection. The groups of patients
      categorized as to improvement or not of the Marder score did not show differences
      in the daily dose. The anti-Xa activity was higher in patients with regression of
      thrombosis compared with patients without regression. The other coagulation
      parameters did not show any relation to the clinical outcome of thrombus
      regression. The relationship between the change of the Marder score at day 10 and
      the anticoagulant effect on the different coagulation systems correlated weakly
      for patients receiving unfractionated heparin. The highest correlation was found
      for the improvement of Marder score and thrombin inhibition in the heparin group
      with r = 0.42. For LMW heparin no correlation could be detected. Heptest
      coagulation values were in the same range for patients receiving unfractionated
      and LMW heparin. In contrast to the chromogenic anti-Xa assay, aPTT, thrombin
      clotting time, and prothrombin time values differed substantially in the two
      treatment regimens. Treatment of recent deep vein thrombosis with unfractionated
      heparin profits from laboratory monitoring, whereas monitoring of the
      anticoagulant effect during the treatment with s.c. LMW heparin does not
      influence the outcome on thrombus regression.

PMID- 9156417
TI  - Experience with antithrombin concentrates in neurotrauma patients.
AB  - Plasma coagulation results from 2,100 injured patients were sequentially and
      systematically evaluated in a large natural history study of neurotrauma. A
      significant correlation became apparent between the severity of and morbidity
      from head injury and the degree of abnormality in coagulation results, especially
      for young injured victims. Subsequent studies in the United States, Europe, and
      Japan have supported the significant correlation between final clinical outcome
      and these measurements of plasma coagulation, as well as inflammatory proteins,
      performed soon after injury. This discussion reviews the data from many published
      reports that support this conclusion, especially data that corroborate the strong
      clinical association between head trauma and disseminated intravascular
      coagulation (DIC). The data that demonstrate a high predisposition for head
      injured individuals to develop DIC serve as a the rationale for therapeutic
      intervention with coagulation protease inhibitors, especially antithrombin (AT).
      A large, double-blind, placebo-controlled trial that evaluates the therapeutic
      use of AT concentrate for DIC in such patients has yet to be completed. Described
      here is the design for such a clinical trial that examined the impact of
      mortality as an outcome. However, this trial was terminated for nonscientific
      reasons soon after it began. Very truncated data collected from this aborted
      study support both the scientific rationale for and the feasibility of such a
      study in the future. Data from such a clinical trial are needed to support the
      use of AT concentrate to treat DIC in this and other morbid diseases.

PMID- 9156416
TI  - Treatment of deep vein thrombosis with low-molecular-weight heparins: a consensus
      statement of the Gesellschaft fur Thrombose-und Hamostaseforschung (GTH).
AB  - Recent studies have led to a new concept for the management of deep vein
      thrombosis. The German Society on Thrombosis and Haemostasis decided to work up
      the clinical studies in this field published until June 1996 for a consensus
      statement. The consensus group concluded that (1) high-dose, APTT-controlled
      subcutaneous administration of unfractionated heparin is as effective as high
      dose, APTT-controlled continuous intravenous infusion of unfractionated heparin
      (grade B recommendation); (2) the anticoagulation with heparin may start at day 1
      or 2, overlapping with oral anticoagulants for 7 to 10 days (grade C
      recommendation); (3) high-dose subcutaneous low-molecular-weight heparins are
      almost as effective and safe as continuous intravenous infusion of unfractionated
      heparins (grade B recommendation); (4) no agreement was obtained for the other
      concomitant treatments of DVT, such as duration of bed rest, use of
      antiphlogistic drugs, whether LMW heparins are comparable, and whether outpatient
      treatment can be recommended using LMW heparins.

PMID- 9156418
TI  - Acquired antithrombin deficiency following severe traumatic injury: rationale for
      study of antithrombin supplementation.
AB  - Hemorrhage, head injury, and multiple organ dysfunction are the most frequent
      causes of mortality in patients who experience severe injury. Acceleration of the
      coagulation cascade is known to result in hemorrhage secondary to disseminated
      intravascular coagulation (DIC) and end-organ dysfunction, as manifest by
      pulmonary and renal failure. Few studies have been conducted to evaluate the
      effects of injury on the endogenous anticoagulants that inhibit excessive
      coagulation activation. We evaluated a group of patients following severe injury
      and found that procoagulant markers (prothrombin fragment 1.2, thrombin
      antithrombin complexes, and D dimers) were significantly elevated for the
      population as a whole. Levels of circulating endogenous anticoagulants
      [antithrombin (AT) and protein C] were relatively unchanged for the total
      population. However, patients with adverse outcomes [DIC and adult respiratory
      distress syndrome (ARDS)] had significant reductions in AT and protein C
      activities. Decreased levels of AT and protein C 8 hours after admission served
      as independent predictors of both DIC and ARDS. Prospective, randomized studies
      should be conducted to evaluate the effect of supplementation of these factors
      after severe injury has occurred.

PMID- 9156419
TI  - Risks and benefits of pediatric bone marrow donation: a critical need for
      research.
AB  - Healthcare providers assume that there are minimal risks and potential
      psychosocial benefits for children who undergo a bone marrow harvest for the
      benefit of their critically ill siblings. Ethical justifications for the use of
      children as donors rely on there being minimal risks since donors receive no
      direct medical benefits from the intervention. There is little empirical research
      regarding psychosocial consequences. This article review relevant research in
      three contexts: a) psychosocial outcomes for adults and children who donate
      tissue and organs; b) psychosocial impacts on a sibling of a pediatric cancer
      patient; and c) children's decision-making regarding medical decisions. The
      relevant research literature supports the belief that the psychosocial impact on
      a child bone marrow donor will be influenced by the survival of the recipient,
      the age of the donor, and the donor's participation in the decision to donate. In
      order to empirically validate the actual psychosocial risks (and benefits) for
      donors, it is argued that direct research is needed so that a donor's well-being
      can be protected.

PMID- 9156420
TI  - The genetic testing of children for cancer susceptibility: ethical, legal, and
      social issues.
AB  - Genetic testing for cancer susceptibility raises many ethical, legal, and social
      concerns, particularly when testing children is also considered. The complexity
      of defining medical and psychosocial risks and benefits of genetic predisposition
      testing for multifactorial disorders, like cancer, is discussed. Presumed
      incompetence of children and adolescents and questionable ability of many adults
      to understand complex genetic information raise informed consent questions.
      Guidelines can aid professionals but there must also be a means of evaluating
      individual cases. Further research is needed to determine optimal methods of
      educating children and adults about genetic issues and to discriminate factors
      which contribute to satisfaction with decision-making about genetic testing.
      Legal issues and practical considerations are examined involving a duty to warn
      family members about genetic susceptibility and to recontact previously-tested
      individuals as knowledge advances. Recommendations are offered concerning roles
      for social scientists and legal scholars in ethical integration of genetic
      testing into our medical and social framework.

PMID- 9156421
TI  - Genetic discrimination and the employment provisions of the Americans with
      Disabilities Act: emerging legal, empirical, and policy implications.
AB  - The Americans with Disabilities Act of 1990 (ADA) is the most comprehensive
      federal civil rights law addressing employment discrimination against potentially
      millions of Americans. The Human Genome Project (HGP) is a federally funded
      research effort that seeks to map and sequence every human gene. This article is
      meant to contribute to the emerging dialogue on the interplay between the HGP and
      the employment provisions of the ADA, set forth in the Title I of the act. The
      relevance of the HGP to emerging legal questions, including those arising under
      Title I and recent EEOC guidelines, is described. Thereafter, empirical issues
      are discussed, and directions for future investigation of genetic discrimination
      under the ADA are explored.

PMID- 9156422
TI  - Dissecting people and ignoring social structure: an analysis of individualism,
      public policy, and genetic labeling.
AB  - Genetic developments are examined from the vantage point of a social problems
      perspective, focusing on their tendency toward reinforcing individualism and
      undermining social structural analyses. The special situation of children is
      considered, with reference to the impact of genetic assessments of anti-social
      behavior, illegitimacy, intelligence, and the problem of genetic labeling. A
      research agenda for the future is suggested which recommends a realignment of
      priorities between genetic and social research.

PMID- 9156423
TI  - Professional responsibility in elder law: a synthesis of preventive law and
      therapeutic jurisprudence.
AB  - This article focuses on the professional responsibilities that a lawyer owes to
      older clients. Specifically, this article proposes that when working with older
      clients, lawyers have a responsibility to ensure that their clients have the
      capacity to manage their own affairs and to ensure their clients' legal,
      financial, and personal interests are protected in case of sudden future
      incapacity. Furthermore, a lawyer working with older clients has a responsibility
      to remain cognizant of the realities of ageing without giving in to the falsities
      of senior citizen stereotypes. Through an integration of Therapeutic
      Jurisprudence and Preventive Law, a proactive, client-centered, four-stage
      framework for advancing therapeutic goals through preventive lawyering is
      developed. The framework is then applied to a model lawyer/client interaction
      typical of elder practice. The advantages and limitations of the four-stage
      framework are discussed.

PMID- 9156424
TI  - A blueprint for lead hazards.
AB  - OSHA has been criticized heavily during the last decade for not providing
      construction workers the same level of protection afforded employees in general
      industry. Now that it has adopted this standard, it would not be surprising if it
      decided to flex its newfound muscle by targeting the construction industry for
      lead inspections this spring. It is January now, and construction activity in
      most of the country will be slow until March or April. Smart contractors should
      use this slack time to formulate a compliance strategy, weigh their options and
      develop a management plan. It is also a good time to begin obtaining cost
      estimates for air monitoring, ventilation equipment, hygiene facilities and
      medical surveillance.

PMID- 9156425
TI  - Job re-design, not 'quick fixes,' thwarts many back injury hazards.

PMID- 9156426
TI  - Behavior-based task analysis prompts early response to ergonomic problems.

PMID- 9156427
TI  - Transform fear to trust: communicating about unsafe job incidents and settings.

PMID- 9156428
TI  - Exposure control plans define risks for bloodborne pathogen infections.

PMID- 9156429
TI  - Proposed tuberculosis standard tests accelerated rulemaking.

PMID- 9156430
TI  - Cutting fluids expose metal workers to the risk of occupational dermatitis.

PMID- 9156431
TI  - OSHA publishes proposed indoor air rule.

PMID- 9156432
TI  - Contractors cited in lead exposure.

PMID- 9156433
TI  - Detecting invisible risks.

PMID- 9156435
TI  - Study options on respiratory protection before permitting confined space entry.

PMID- 9156436
TI  - Foam products plant institutes policies for reducing repetitive motion illnesses.

PMID- 9156437
TI  - Lasers & vision: high-powered revision.

PMID- 9156438
TI  - In plane view: blind spots and visual limits.

PMID- 9156439
TI  - Chronic risk in construction.

PMID- 9156440
TI  - Well-designed air control systems diminish exposure to lead and acid.

PMID- 9156441
TI  - Poor posture subjects a worker's body to muscle imbalance, nerve compression.
AB  - Forward head and shoulder postures and associated muscle imbalances are prevalent
      among today's workers, according to ongoing research in the physical therapy
      field. Information on proper posture should be used proactively to educate
      employees as part of injury prevention training. Maintaining muscle strength in
      the desirable posture will require ongoing exercise and attention from the
      worker. The self-direct approach will not eliminate all cases of tendonitis,
      epicondylitis and other disorders, but it will have a significant positive
      impact.

PMID- 9156442
TI  - Company's exercise program mobilizes its industrial athletes before work.

PMID- 9156443
TI  - Fabrics that repel.
AB  - When exposures to hazardous chemicals cannot be eliminated through engineering
      changes, substitution of different materials, or implementation of alternative
      work practices, chemical protective clothing offers the last line of defense. No
      single material provides protection against all chemicals, and selection of the
      appropriate CPC is governed by the nature of the hazard, the chemical resistance
      properties of the protective material and the conditions under which the
      equipment will be used. Merely making protective equipment available to employees
      is not sufficient. The equipment must be properly selected, used and maintained.
      Torn suits or punctured gloves, for instance, do not provide very much
      protection. A good protective clothing program must also include provisions for
      employee training and ongoing supervision.

PMID- 9156444
TI  - Sick of the system?

PMID- 9156445
TI  - Alarming readings.
AB  - The confined space standard has spawned a proliferation of confined space
      instruments. Careful reading of published specifications shows that some
      instruments are not suited for confined space testing. Therefore, it is important
      to read and understand those boring, mind-numbing specifications before making an
      instrument purchase.

PMID- 9156446
TI  - A deluge can save the eyes.

PMID- 9156447
TI  - The 'ABCs' of noise measurements set the stage for responsive controls.

PMID- 9156448
TI  - NIOSH respirator testing rules give industry some breathing room.

PMID- 9156449
TI  - 1994 National Safety Congress goes west for leading perspectives.

PMID- 9156450
TI  - Health care reform should include worksite health promotion incentives.

PMID- 9156451
TI  - Is CPR training based on practice that ensures reliable performance?

PMID- 9156452
TI  - Waste away.

PMID- 9156453
TI  - The role of the human spirit in recovery from injury.

PMID- 9156454
TI  - 'Odd' engineering technology adjusts workers' exposure to tobacco smoke.

PMID- 9156455
TI  - Weighing the evidence.

PMID- 9156456
TI  - Class distinctions. Those who don't distinguish their flammable liquids'
      flashpoint classes, storage specifications and compliance codes can wind up
      trying to extinguish a blaze.

PMID- 9156457
TI  - Eyewear lenses change shape, tint for protection in wide variety of jobs.

PMID- 9156459
TI  - Lumbar support most critical feature to consider during chair selection.

PMID- 9156458
TI  - Tactics against workplace hearing loss motivate employees to wear protection.

PMID- 9156460
TI  - Footwear alleviates aches, fatigue through better fit, shock absorption.

PMID- 9156461
TI  - Prompt diagnosis, treatment critical in workplace burn emergency response.

PMID- 9156462
TI  - The public and private faces of eighteenth-century London dispensary charity.

PMID- 9156463
TI  - Capital, profession and medical technology: the electro-therapeutic institutes
      and the Royal College of Physicians, 1888-1922.

PMID- 9156464
TI  - The immunization of cattle against rinderpest in eighteenth-century Europe.

PMID- 9156465
TI  - Occupational health during the Second World War: hope deferred or hope abandoned?

PMID- 9156466
TI  - Illustrations from the Wellcome Institute Library. Wellcome and Osler.

PMID- 9156467
TI  - Occupational stress management programmes: a practical overview of published
      effect studies.
AB  - There are many occupational stress management programmes available which are
      designed to prevent and cure the negative aspects of job-stress. The focus of the
      programmes can be directed towards the individual worker, the working group, the
      organization of the work or the organization as a whole. Moreover, programmes
      show a considerable variation with respect to the type of interventions they
      promote and their underlying assumptions, as well as their duration and costs. In
      this paper, effect studies of occupational stress programmes published between
      1987 and 1994 are reviewed. The aim is to give a practical overview of the
      variety in occupational stress programmes, their scope, applicability and the
      evidence of their effectiveness. The paper updates the review by DeFrank and
      Cooper published in 1989.

PMID- 9156468
TI  - Shift work and risk factors for coronary heart disease in Japanese blue-collar
      workers: serum lipids and anthropometric characteristics.
AB  - This study was conducted to determine if there is an association between shift
      work and risk factors for coronary heart disease (CHD) in Japanese male blue
      collar shift workers. Health check-up data on serum lipid concentration and
      anthropometric indices of 33 three-shift workers and 27 two-shift workers were
      compared with those of day workers. The average years in age of the shift workers
      and day workers were 34.5 (SD = 7.1) and 32.7 (SD = 7.6), respectively. Serum
      total cholesterol levels of three-shift, two-shift and day workers were 5.70 (SD
      = 1.19) mmol/l, 4.81 (SD = 1.01) mmol/l, 4.98 (SD = 0.95) mmol/l, respectively,
      and the cholesterol levels of three-shift workers were significantly higher than
      the other workers (p < 0.05). In addition, the abdominal to hip circumference
      ratios were 0.905 (SD = 0.060) for three-shift workers and 0.877 (SD = 0.054) for
      day workers, with a significant difference (p < 0.05). In the present Japanese
      population, three-shift workers had higher risks of CHD than day workers, which
      was characterized by higher levels of serum total cholesterol and tendency to
      central obesity. These findings held when lifestyle factors were taken into
      account.

PMID- 9156469
TI  - Risks associated with occupational glass injury in bar staff with special
      consideration of hepatitis B infection.
AB  - Since bar workers often sustain cuts from unwashed bar glasses, the aims of this
      study were to investigate risk of injury and to examine the sero-prevalence of
      markers for hepatitis B amongst bar staff. Ninety-one bar staff recruited by
      newspaper advertisement were asked about injury experience and life-style risks
      associated with transmission of hepatitis B and were tested for hepatitis B
      surface antigen (HBsAg) and core antibody (anti-HBc). Seventy-four per cent
      reported lacerations from broken glassware at work: 18% had sustained such
      injuries in more than 10 incidents. Fifty-five per cent of respondents reported
      occupational skin contact with body fluids. Anti-HBc prevalence for the study
      group was 1.1%, suggesting that bar staff were not at increased risk from
      hepatitis B infection. Although 30% wore gloves for high-risk tasks, there was no
      evidence that glove wearing prevented glass lacerations. This level of injury
      experience and exposure to body fluids is unacceptable and represents a potential
      risk of cross-infection. Hepatitis B immunization should be considered in this
      group. Urgent action, including the replacement, wherever possible, of annealed
      with tempered bar-glassware, is necessary to protect bar workers from glass
      injury.

PMID- 9156470
TI  - Circadian rhythms of arterial pressure, heart rate and oral temperature in truck
      drivers.
AB  - Circadian rhythms of arterial pressure (AP), heart rate (HR) and oral temperature
      (OT) were studied in healthy male truck drivers and in a control group of air
      traffic controllers. Twenty-four-hour records of systolic and diastolic AP and HR
      and of OT were obtained from 12 truck drivers both during the outward and
      homeward journey in Europe and Asia, and from 12 air traffic controllers during a
      morning shift. Data were analyzed by the cosinor method. The results obtained in
      the control group were as follows (mesor/amplitude/acrophase): systolic AP (mm
      Hg): 111.1/6.1/16.51 h; diastolic AP: 68.4%5.6/16.58 h; HR (b.p.m.):
      77.07/7.6/17.46 h; OT (dg C): 36.74/0.21/17.26 h. Statistically significant
      acrophase advances were observed for the circadian rhythms of systolic, diastolic
      and mean AP and of HR in TD during the outward journey in comparison with the
      control ATC group. These differences were still present during the homeward
      journey, in combination with an acrophase delay of the circadian rhythm of OT.
      Our results supply grounds to suppose that extended working time combined with
      greater load during a long-lasting trip may act to generate an internal
      desynchronization of circadian rhythms in long-haul truck drivers.

PMID- 9156471
TI  - A survey of starch particle counts in the hospital environment in relation to the
      use of powdered latex gloves.
AB  - As latex proteins, which cause latex hypersensitivity, can be found on starch
      particles and inhalation may be a route for sensitization, the presence of starch
      particles in hospital air was examined. The starch particles were demonstrated by
      immobilization onto cellulose acetate filters and staining with iodine. Rooms in
      which powdered latex gloves were used gave counts of up to > 3,667 particles per
      cubic meter of air. Starch particles were not found in the air in rooms where
      latex gloves were not used, and were highest in rooms with a high glove usage but
      no ventilation. A change to powder-free gloves significantly reduced the count of
      starch particles in the unventilated Accident/Emergency Department air. Use of
      powder-free gloves should be considered especially in unventilated areas in
      healthcare premises.

PMID- 9156472
TI  - Hempson Industries UK Ltd.. A case study in occupational health services--the
      solution.
AB  - In the February 1996 issue of Occupational Medicine, we published a case study in
      which the Chief Medical Officer of Hempson Industries, Steve Saunders, had just
      returned from a European conference where he delivered a well-received keynote
      presentation on work-related stress disorders. He was delighted with this success
      and his more general success in establishing a professional and proactive
      occupational health service during his two years with Hempson Industries. His
      delight, however, was undermined by his receipt of an internal memorandum from
      the newly appointed Director of Finance and Administration, Richard Coleman. The
      letter cited Board colleagues' criticisms of the contribution of OHS to company
      results, the expense of some services like health screening and recruitment
      medicals and the seemingly slow and unresponsive behaviour of most OHS staff. It
      also proposed the out-sourcing of occupational health to Boone Occupational
      Health Care Inc., an American private occupational health service. We invited
      readers to reply to the case study, explaining what they would do in Steve's
      situation. Out of a number replies, four were selected for publication and
      follow. The author author of the case study, Greg Shaffer, then provides some
      final comments.

PMID- 9156473
TI  - How I prepare a programme proposal.
AB  - Selling occupational health is not easy. A well-structured proposal is necessary
      to convince employers that occupational health is valuable to the company and
      cost-beneficial aspects need to be emphasized.

PMID- 9156475
TI  - Partnership.

PMID- 9156474
TI  - The heritage of Bernardino Ramazzini.
AB  - Although the seminal work in what was to become the specialty of occupational
      medicine appeared in 1700 as written by the Italian physician, Bernardino
      Ramazzini and titled De Morbis Artificum Diatriba, it was through the English
      translation by Wilmer Cave Wright in 1940 and and the subsequent scholarship of
      Dr Pericle Di Pietro of Modena, Italy, that this monograph became widely known.
      Ramazzini has been cited by innumerable medical authors and his volume has
      undergone many translations from the mid-18th century to the present day.
      References to this early observations of persons and work and their subsequent
      disease patterns repeatedly infuse today's description of work-related illness.
      That his pioneering efforts continue to receive adulation is seen in the
      organizations bearing his name, many eponymous awards, the striking Ramazzini
      Hall in Japan, and the continuing appearance of new reprintings of Diseases of
      Workers world-wide. The name Ramazzini marks the beginning of society's concern
      with the well-being and physical and emotional health of its workers from the
      shops of the crafts to the offices of the executives.

PMID- 9156476
TI  - Ocular trauma in an iron forging industry in the eastern province, Saudi Arabia.
AB  - Occupational accidents occur in industry worldwide, and the Kingdom of Saudi
      Arabia (KSA) is no exception. However, accidents are not routinely analyzed in
      this country and therefore their extent and types remain unknown. The aim of this
      study was to calculate the rates of ocular injuries in an iron forging factory in
      the Eastern Province of the KSA. It also aimed at identifying the main causes of
      injury and the groups at risk. All ocular and non-ocular injuries that occurred
      during 1991 were reviewed. Data sources were the company's accident report and
      the employees' medical files. A total of 193 injuries were reported. Seventy
      seven (39.9%) of these affected the eyes. The incident rate for ocular injuries
      was 111.8 per 1,000 men exposed. The age group 33-42 had the highest prevalence
      rate (55.8%) and 67.5% of the eye injuries involved employees with job experience
      of 11 months or less. Use of pneumatic chisels was among the most hazardous
      activities. Projectile foreign bodies were responsible for 76.6% of the
      incidents. More than a third of the injured were not wearing eye protection.
      Avoidable factors, such as negligence, were major contributory factors. A
      training programme concerning safety has much to commend it, and pneumatic
      chisels should be replaced by other safer means.

PMID- 9156477
TI  - Occupational safety and health: a method to test the collection of 'grey data' by
      line managers.
AB  - This paper describes and discusses a method for collecting data relating to the
      potential for illness or injury to occur in an organization. The reason for using
      the term 'grey' is explained and the underpinning philosophy of fuzzy thinking is
      also discussed. The method used was an audit which attempted to measure the
      degree to which certain types of failure were present in one organization. The
      audit used a term approach in design and execution and was found to be a useful
      and useable tool for collecting information relating potential causes of injury
      or illness.

PMID- 9156478
TI  - Erythrocyte cholinesterase activity levels in desert farm workers.
AB  - In this study we have examined 532 migrant farm workers engaged mainly in the
      cultivation of vegetable crops, in both greenhouses and openfarms, and an equal
      number of controls. Erythrocyte acetylcholinesterase activity (AChE) was measured
      to determine the degree of toxicity due to exposure to organophosphate and
      carbamate pesticides in the farm workers employed either as foremen (41.5%) or
      farmers (58.5%). The mean ages of the farm workers and controls were 35.2 +/- 7.4
      (mean +/- SD) years and 34.6 +/- 7.1 years. AChE activity of the farm workers and
      controls was 3.89 +/- 0.64 UI/ml (mean +/- SD) and 4.15 +/- 0.29 UI/ml. The
      haemoglobin adjusted erythrocyte cholinesterase activity (HAChE) was 29.96 +/-
      4.14 (mean +/- SD) for farm workers and 32.10 +/- 2.26 for controls. AChE
      activity was very highly significantly lower for the foremen (3.76 +/- 0.69)
      compared to farmers (3.98 +/- 0.59) (Student's t-test = 4.13, p = 0.0001). HAChE
      was also very highly significantly lower for foremen (29.24 +/- 4.37) compared to
      farmers (30.46 +/- 3.88) (Student's t-test = 3.64, p = 0.0001). The poorly
      controlled used of pesticides in the farms appeared to have caused sub-clinical
      intoxication in the farm workers and indicated the need for training and
      implementation of hygiene practices.

PMID- 9156479
TI  - Evaluation of occupational health service in the wood processing industry-
      determination of employee satisfaction.
AB  - In order to define priorities for improvement of the occupational health service
      (OHS) in one primary health care unit, employees' satisfaction was evaluated with
      a postal questionnaire. The questionnaire covered items on service reservation,
      personal health education received, quality of the OHS, and use of the OHS within
      six months by the employees. This evaluation was one step of the quality system
      that was planned in accordance with the ISO 9004-2 standard for continuous
      quality improvement of OHS. The study population was all of 1,050 employees
      working for five employers; 546 (52%) employees responded to the inquiry.
      However, only 377 of them had made use of the OHS within the last six months
      before the inquiry. The mean age of the responders was 42 years (SD = 9 years)
      and 76% of the respondents were men. The percentages of employees with a high
      degree of satisfaction with the quality of the OHS and personal health education
      in the OHS were 76% and 69%, respectively. However, concerning the quality of the
      OHS, the proportion of highly satisfied employees was 27% higher (95% CI = 19
      35%) among those who had used OHS within six months compared to the others.
      Furthermore, when the oldest (> 48 years) and the youngest (< 35 years) age
      groups were compared, the difference between the proportions of highly satisfied
      employees was 21% (95% CI = 31%). In conclusion, the high differences suggest a
      close linkage between the employee's satisfaction with the OHS, the use of the
      OHS and ageing.

PMID- 9156480
TI  - The impact of the COSHH regulations on workers with occupational asthma.
AB  - In the UK, the COSHH Regulations give specific guidance that employers have
      duties to inform, instruct and train their employees about occupational risks and
      provide them with suitable health surveillance. The aim of the study was to
      evaluate the impact of the Regulations on employees with occupational asthma. One
      hundred consecutive patients attending an occupational lung disease clinic
      completed a questionnaire assessing the implementation of the COSHH Regulations
      in their workplace. Twenty-eight per cent had a pre-employment inquiry about
      asthma, 31% had regular health surveillance by questionnaires and 19% had regular
      lung function assessment at work. Pre-employment spirometry was carried out in
      44% of the workers who were exposed to one of the original seven prescribed
      agents, significantly more than those who were exposed to other agents (19%) (p <
      0.05). Moreover, figures for spirometry during employment were 31% and 8%
      respectively (p < 0.05). The patients who worked after 'COSHH' but before 'MS25'
      had a tendency to be provided with health surveillance more than those who worked
      after both 'COSHH' and 'MS25'. Ninety-one per cent of the patients had never been
      informed about the risks of getting asthma at work and 73% had never seen the
      safety data sheets. The workers who (1) worked after 'COSHH' introduction; (2)
      worked in larger firms and (3) were exposed to one of the original seven
      prescribed' agents, had a tendency to be informed, instructed and trained more
      than the rest. However, there were only significant statistical differences (p <
      0.05) in terms of the safety data sheet position between the cases who worked
      before the time of the legislation and those employed afterwards.

PMID- 9156481
TI  - Ventilatory function of factory workers exposed to tea dust.
AB  - A cross-sectional study was conducted in order to determine the prevalence of
      respiratory symptoms and the effect on ventilatory capacity in workers exposed to
      tea dust for at least five years during the sifting process of tea manufacture
      compared to a control group of field workers who were not exposed to tea dust
      previously. Fifty-three subjects each in the study and control groups were
      matched for age, sex, ethnic group and height. Prevalence of chronic respiratory
      symptoms was obtained by questionnaire. Spirometric measurements included forced
      vital capacity (FVC), forced expiratory volume in the first second (FEV1.0) and
      forced mid-expiratory flow rate (FEF 25-75%). The study group had a chest
      radiograph. The odds ratio for any chronic respiratory symptom was 11.6 (95%
      confidence interval [CI] = 3.7-39.4) in the study group. Mean values for the
      spirometric tests were lower in the study group; the differences in FEV 1.0 and
      FEF 25-75% were significant. Tuberculosis was not found in the study group, while
      one subject (2.4%) had radiological evidence of bronchiectasis. It may therefore
      be concluded that chronic tea dust exposure causes increased prevalence of
      respiratory symptoms and a significant degree of small airways obstruction.

PMID- 9156483
TI  - Assessment of disability under the Social Security Industrial Injuries Benefit
      Scheme.

PMID- 9156482
TI  - Ethics and the occupational physician.

PMID- 9156484
TI  - How the occupational physician works with the unions.
AB  - A few attitudinal and behavioural principles will bring about a productive
      liaison between the occupational physician and trade unions. An effective working
      relationship with these organizations and employee associations can be developed,
      provided the occupational health care professionals are impartial in their
      practice, the loyalty to medicine replacing any bias toward the favouring of a
      managerial view. Respect must be given union officials, for in their organization
      they have status and can advance or defeat various health programs. Union
      representation on an occupational health committee will gain union support and
      minimize the filing of health-based grievances. The presentation of occupational
      health information at union meetings will communicate the goals of in-plant
      programs and familiarize workers, through their accustomed channels, with the
      objectives of health care policies and procedures.

PMID- 9156485
TI  - Gastrointestinal upset in a frequent traveller.

PMID- 9156486
TI  - Tuberculosis: the case for vigilance.

PMID- 9156487
TI  - Occupational asthma: a GP's guide.

PMID- 9156488
TI  - All that wheezes is not asthma.

PMID- 9156490
TI  - Pointers for passing the CRQ. Part 2.

PMID- 9156489
TI  - National guidelines on dyspepsia.

PMID- 9156491
TI  - On the scent of asthma.

PMID- 9156492
TI  - A family history of breast Ca.

PMID- 9156493
TI  - Current thinking on psoriasis.

PMID- 9156494
TI  - Managing PLE and actinic prurigo.

PMID- 9156495
TI  - Urticaria: a rational GP approach.

PMID- 9156496
TI  - Mouth ulcers: how can you help?

PMID- 9156498
TI  - MRCGP: sound advice from the administrator.

PMID- 9156497
TI  - Antibiotics: what is the current position?

PMID- 9156499
TI  - When doctors see red.

PMID- 9156500
TI  - Interspeaker variability in emphatic accent production in French.
AB  - This research aims (1) to describe the acoustic manifestations of emphatic accent
      in French by examining similarities and differences between four speakers; and
      (2) to identify, amongst the acoustic measures, those which determine the
      perception of emphasis. In experiment 1, four speakers were asked to read twenty
      four sentences aloud twice, first without any emphasis, and second with emphasis
      on a target word in the sentence. The acoustic modifications induced by emphasis
      production were analyzed on the target words and on their surrounding contexts,
      speaker by speaker. Acoustic measurements revealed that all speakers increased
      the contrast between the target and the contexts, by slowing down articulation on
      the targets and by increasing intensity and F0 on the targets relative to the
      adjacent syllables. F0 peak was found either on the first or last syllable of the
      target word, and F0 increase was shown to spread over the peak-bearing syllable
      to the whole word. Speakers' productions differed with respect to the production
      of pauses and the syllabic location of F0 peak in the target words. In Experiment
      2, the four speakers' productions were presented to listeners, who had to decide
      whether an emphasis had been produced or not. A stepwise regression analysis was
      conducted, using the acoustic measurements as independent variables and the
      percentage of emphasis perception as the dependent variable. The results suggest
      a major role of F0 manifestations: Listeners were found to be sensitive to an F0
      increase on the first syllable of the target, relative to its value in non
      emphasis condition. Listeners would be sensitive to deviations from expected F0
      patterns in French, and may interpret them as signaling emphatic accent.

PMID- 9156501
TI  - [Management of hematoma of the nasal septum and abscesses of the nasal septum].

PMID- 9156502
TI  - [Inverted papilloma of the nose and paranasal sinuses].
AB  - BACKGROUND: Inverted papilloma is a rare benign tumor of the nose and the
      paranasal sinuses. There is a controversial discussion concerning the operative
      approach. The epidemiology, postoperative results, and recurrence rates of
      endonasally and extranasally operated patients are analysed. PATIENTS: Between
      1984 and 1995, 25 patients with inverted papilloma were operated upon at the ENT
      Department St. Gallen, 18 patients by an endonasal microscopic approach, two by
      midfacial degloving and five through a lateral rhinotomy. RESULTS: After a
      minimal follow-up of 12 months (mean follow-up 52 months), a recurrence rate of
      29% for the external approach and 31% for the endonasal approach was observed.
      CONCLUSIONS: In most cases it is possible to achieve a good result through an
      endonasal approach. External approaches are recommended in T4-tumors or
      carcinomas. A longtime follow-up is recommended for each case.

PMID- 9156503
TI  - [Drug treatment of invasive aspergillosis of the paranasal sinuses].
AB  - Aspergillosis belongs to the group of mycotic diseases of the paranasal sinuses.
      The invasive forms, and particularly the fulminant forms, are potentially fatal.
      Primary surgical intervention with complete removal of the mycotic mass should be
      performed. Additionally an antimycotic drug therapy with amphotericin B must be
      started. In a review of the literature, there is no case surviving an extended
      invasive aspergillosis after failure of the operative therapy and after failure
      of the postoperative amphotericin B treatment. We report an interesting case of a
      complete remission of an invasive, partially fulminant aspergillosis of the
      paranasal sinuses and frontal and basal regions. After incomplete removal of the
      mycotic mass by an endo- and extranasal approach, we started postoperative drug
      therapy with amphotericin B. Under this treatment the mycosis progressed.
      Additionally the patient developed severe renal side effects requiring suspension
      of the treatment. At this time, we started a combined antimycotic drug therapy
      with liposomal amphotericin B (AmBisome) and itraconazol. Within 10 weeks there
      was complete clinical and radiologic remission. The patient died 63 weeks after
      this treatment because of a fulminant bacterial pneumonia. Post mortem
      examination showed no aspergillosis in the skull base, the paranasal sinuses, or
      in the lung. The question arises as to whether this drug combination of liposomal
      amphotericin B (AmBisome) and itraconazol is a real alternative to high-risk
      surgical interventions in this region.

PMID- 9156504
TI  - [Possibility for quantitative and frequency-specific assessment of auditory
      threshold with otoacoustic emissions].
AB  - BACKGROUND: Otoacoustic emissions can be used to study cochlear function in a non
      invasive manner. They are an effective clinical tool for infant hearing
      screening. The purpose of this study was to determine their utility for a
      frequency-specific and quantitative estimation of the hearing threshold. METHODS:
      Transiently evoked otoacoustic emissions (TEOAE) and distortion-product emissions
      (DPOAE) were recorded from 16 normal and 86 hearing impaired ears and correlated
      with their hearing threshold between 0.5 and 6.0 kHz. RESULTS: The correlations
      of TEOAE and the hearing threshold ranged from 0.53 (0.5 kHz) to 0.69 (6.0 kHz),
      of the DPOAE from 0.51 (0.5 kHz) to 0.83 (6.0 kHz). Based on the optimal
      correlating OAE frequency we tried to predict the hearing threshold. We obtained
      95% prediction intervals for TEOA between 19 dB (1.0 kHz) and 39 dB (4.0 and 6.0
      kHz), for DPOAE between 21 dB (1.0) and 34 dB (3.0 and 4.0 kHz). CONCLUSION:
      Despite their clinically irrelevant greater prediction intervals at the low
      frequencies, our results suggest that DPOAEs are generally more valuable for the
      frequency-specific estimation of the hearing threshold. Prediction intervals may
      improve the interpretation of OAEs.

PMID- 9156505
TI  - [Effects of standardized Myrtol in therapy of acute sinusitis--results of a
      double-blind, randomized multicenter study compared with placebo].
AB  - BACKGROUND: In the management of non-purulent acute sinusitis, alpha adrenergic
      substances are administered topically and secretolytics systemically. Antibiotic
      therapy should be restricted to purulent forms. This study was designed to
      demonstrate the importance of the maintenance of permanent ventilation and
      drainage of the sinuses as a therapeutic concept. PATIENTS/METHODS: In a
      multicentric trial the efficacy and safety of myrtol standardized and another
      essential oil were investigated in 331 patients with acute sinusitis in
      comparison to placebo. Three hundred thirty patients were evaluated in an intent
      to-treat-analysis and 291 patients remained for statistical analysis. The study
      was conducted in 16 centers in a double-blind, double-dummy, randomized design
      versus placebo. During an observation-period of 14 days the patients were treated
      for 6 +/- 2 days with the respective study medication. RESULTS: With respect to
      efficacy, both myrtol standardized and the other essential oil proved to be
      significantly superior to placebo. As to the tolerance, a slight advantage of
      myrtol standardized was demonstrated in comparison to the other verum substance.
      CONCLUSION: These results which do support the value of essential oils like
      myrtol as an effective treatment in acute, uncomplicated sinusitis instead of
      antibiotics as first choice, are confirmed by the existing literature.

PMID- 9156506
TI  - [Chondrosarcoma of the larynx].
AB  - BACKGROUND: Manifestation of chondrosarcoma (CS) in the head and neck region is
      rare but it is the most frequently encountered non-epithelial malignancy of the
      larynx. Since this tumor entity is frequently neglected, its characteristics
      including differential diagnosis and therapy will be discussed in the following.
      PATIENTS: From 1975 to 1995, five cases with CS were diagnosed and treated in the
      Department of Otorhinolaryngology, Head and Neck Surgery, University of Kiel.
      RESULTS: The medical history of this five patients (one woman, four men, average
      age: 71 years) varied from 9 months to 10 years. Three patients had a fixation of
      the vocal cord; one patient had obviously reduced movement of the vocal cord. Two
      cases revealed a moderate and three cases a high differentiation in the
      histological examination. Initially one case was diagnosed as a chondroma. The
      origin of tumor growth was the cricoid cartilage in four patients and the
      cartilage of the arytenoid in one patient. Surgical treatment was either by
      partial or complete laryngectomy in two cases each. One patient refused any
      therapy. Two patients including the latter died of tumor related causes.
      CONCLUSIONS: Laryngeal CS grow slowly. Diagnosis is frequently made late in the
      course of disease. Obtaining of tissue for histological examination and
      diagnostic delimitation towards a chondroma can be difficult. Therapy depends on
      the degree of histological differentiation with radical excision of low or
      moderately differentiated CS and function preserving surgery in case of high
      differentiation.

PMID- 9156507
TI  - [Palliative intraoperative irradiation of recurrent neck lymph node metastases in
      the head and neck area].
AB  - BACKGROUND: In the course of a malignant tumor disease, metastases in the
      regional lymph nodes commonly are linked with poor prognosis. Especially in cases
      of recurrence after surgery and radiation therapy, curative management of the
      disease can rarely be achieved. Therefore several palliative treatment modalities
      have been developed. Intraoperative radiation therapy represents one of them it
      allows a single high-dose irradiation of a region which, in light of the global
      tumor disorder, cannot be cured by surgical intervention. METHODS/ PATIENTS:
      Between 1989 and 1994, 70 patients with recurrent metastases in the head and neck
      lymph nodes were treated with IORT in the ENT Department of the University
      Hospital Aachen in collaboration with the Radiation Department. Since some
      patients were irradiated up to four times, 91 operations (77 under general
      anesthesia and 14 under local anesthesia) and irradiations were performed. During
      the procedure each, patient had to be transported twice from the standard
      operating suite to the radiation unit and back. RESULTS: Regarding the palliative
      intention of IORT in these cases, we mainly evaluated parameters which had an
      influence on quality of life of the patients: duration of hospitalization, pain
      treatment, removal of necrotic tumor mass, and safety of treatment. Depending on
      the general condition, the patients stayed in the hospital for 3-56 days (median:
      10 days). In almost every case, mental and to some extent physical integrity was
      restored for some time after the disfiguring tumor on the neck had been removed.
      In nearly 90%, pain treatment could be reduced (e.g., discontinuation of opiate
      treatment) or further progression could be avoided (74%). Despite the
      transportation only few complications occurred, which primarily involved healing
      disturbances (n = 8), fistulas (n = 3), and edemas of the arm (n = 2; after
      primary treatment of breast cancer). There was no serious infection observed
      under prophylactic antibiotic treatment in 74% of the cases. Local tumor control
      (LTC), which only was of minor interest in this treatment group, was possible
      depending on the extent of tumor resection that could be achieved during the
      surgical approach: R0 resection = > 50% LTC/R1 resection = > 40% LTC/R2 resection
      (72.5% of the cases) = > 24.8% LTC. Follow-up of the surviving patients lasted 6
      26 months (mean: 14.4 months) but generally did not allow an exact assessment of
      the time of tumor control. CONCLUSIONS: IORT of recurrent metastases in the head
      and neck region in our opinion represents an effective alternative for palliative
      treatment. Important aspects of the patients' quality of life could be improved,
      and patients were then able to take part in social life again for some time. On
      the other hand tumor control was not to be expected since in most of the cases
      only an incomplete tumor resection was achieved. However, the extent of resection
      substantially affects local tumor control in the head and neck region.

PMID- 9156508
TI  - [Reproducibility of nonradioactive DDRT-PCR method for detection of gene
      expression in squamous epithelial carcinoma cells of the upper aerodigestive
      tract].
AB  - BACKGROUND: The analysis of the gene spectrum in tumor and normal cells may
      provide information about genes involved in the differentiation or in the genesis
      of tumors. Differential Display Reverse Transcriptase Polymerase Chain Reaction
      (DDRT-PCR) is an innovative method that enables quick analysis of almost all mRNA
      molecules expressed in the cells. METHODS: In the trials, the mRNAs of
      keratinocytes and tumor cells were amplified by a number of oligonucleotide pairs
      after reverse transcription and resolved on polyacrylamide gel. A modified
      protocol for the amplification of cDNA probes was devised for detecting PCR
      products with silver nitrate. RESULTS: After reverse transcription of mRNAs, all
      cDNA samples were successfully amplified using the protocol devised for the
      silver nitrate DDRT-PCR, and the differentially expressed fragments were
      reproducibly demonstrated. CONCLUSIONS: The high reproducibility and feasibility
      of silver nitrate DDRT-PCR expand the alternatives for analyzing gene expression
      and detecting selectively expressed genes in different kinds of cells.

PMID- 9156509
TI  - [Protracted course of polychondritis as the etiology of progressive nose
      deformity, subglottic tracheal stenosis and inner ear hearing loss].
AB  - BACKGROUND: Relapsing polychondritis is a rare recurring inflammatory disorder
      with variable clinical course. Its etiopathogenesis is unknown, but autoimmune
      mechanisms are likely to be involved. PATIENT: We present a case report of a 42
      year-old woman with polychondritis manifested in very slowly progressing
      destruction of the nasal cartilage, additional subglottic tracheal stenosis, and
      increasing cochlear dysfunction. RESULT: We describe and document by a series of
      photographs the very protracted course of the disease in this patient from early
      youth until now. Clinical signs and differential diagnosis in polychondritis are
      discussed. CONCLUSION: An early diagnosis in slowly progressing cases like this
      has to be established in order to permit adequate use of glucocorticoids and/or
      immunosuppressive drugs, to check the progress of the disease and prevent
      potentially lethal complications.

PMID- 9156510
TI  - [Isolated extracranial meningioma of the facial soft tissues].
AB  - BACKGROUND: Isolated primarily extracranial meningiomas are extremely rare tumors
      of the head and neck region. The pathogenesis of these benign lesions is not
      fully clarified. Most likely these tumors derive from ectopic meningeal or
      arachnoid cells following the nerve sheaths of cranial nerves along their course
      through the skull base. PATIENT: We report on a patient presenting with a slow
      growing tumor of the soft facial tissue. The tumor was resected completely via an
      external approach. RESULTS AND CONCLUSION: The patient has been free of tumor
      recurrence for one year. The pathogenesis of the extracranial meningioma in this
      patient seems to be the displacement of meningeal cells in the course of a
      fracture of the base of the skull.

PMID- 9156511
TI  - [Case report: a traumatic facial paralysis caused by a fish].
AB  - BACKGROUND: Due to the increase in worldwide tourism more and more unusual
      injuries are observed. CASE: We report on a patient who was diving near the
      Maledives, where a fish weighing 30 kg collided with his head. Four to five hours
      later he suffered from paralysis of the facial nerve. During an operation
      performed after his return a part of the jaw of the fish was removed from the
      retromandibular fossa. The fish jaw had compressed the facial nerve. RESULT:
      Three months later the function of the nerve was normal again. CONCLUSION: Even
      simple accidents require a detailed patient history and the use of computed
      tomography. This made it possible to determine the cause of this unusual facial
      paralysis and cure the patient.

PMID- 9156512
TI  - [Reimbursement claim of an absent director of medicine].

PMID- 9156513
TI  - [Computerized tomography of paranasal sinuses--a preoperative check list].
AB  - BACKGROUND: Computed tomography (CT) is being used increasingly both to evaluate
      location and extent of sinus disease and to detect anatomic abnormalities prior
      to surgery. Analysis of the CT scan should be undertaken in a routine,
      standardized fashion to ensure that important details are not missed. To aid in
      this evaluation, a checklist has been developed which focuses on the most salient
      and potentially dangerous areas of the paranasal sinuses. Regular preoperative
      analysis using this system may prevent unforeseen technical difficulties and
      excess morbidity. MATERIALS AND METHODS: Before obtaining a CT scan, the patient
      is placed on optimal medical therapy including antibiotics, and topical and
      occasionally systemic steroids. Coronal scans are then performed with 3 mm
      sections through the frontal and sphenoid sinuses and 2 mm sections through the
      ethmoid region. Intravenous contrast is used. The study is then analyzed focusing
      on specific critical anatomic landmarks. When additional information is required
      due to severe pathology or atypical anatomy, axial sections are added. RESULTS:
      Out of 300 CT examinations that where analyzed, a preoperative checklist was
      developed with eight items that must be evaluated preoperatively. Methods for the
      identification and analysis of this anatomy as well as the types of anatomic
      variation are discussed. We have found this evaluation to be extremely useful and
      efficacious in preventing morbidity in endoscopic sinus surgery. CONCLUSIONS:
      Evaluation of the preoperative CT examination with a strictly applied checklist
      of important details and landmarks allows the recognition of hazardous anatomy
      and pathology which should increase the safety and efficacy of paranasal sinus
      surgery.

PMID- 9156514
TI  - Developmental expression of the cyclo-oxygenase-1 and cyclo-oxygenase-2 genes in
      the peri-implantation mouse uterus and their differential regulation by the
      blastocyst and ovarian steroids.
AB  - Cyclo-oxygenase (COX) is a rate-limiting enzyme that converts arachidonic acid to
      prostaglandins (PGs) and exists in two isoforms, COX-1 and COX-2. In the rodent,
      increased uterine vascular permeability at sites of blastocyst apposition is one
      of the earliest prerequisite events in the implantation process. This event is
      preceded by generalized uterine edema and luminal closure, and coincides with the
      initial attachment reaction between the trophectoderm and luminal epithelium.
      Vasoactive PGs are implicated in these processes. Here we demonstrate that COX
      genes are differentially regulated in the peri-implantation mouse uterus. During
      the preimplantation period (days 1-4), the COX-1 gene was expressed in the
      uterine epithelium mainly on day 4 until the initiation of attachment reaction in
      the evening after which the expression was downregulated. This COX-1 expression
      coincides with the generalized uterine edema required for luminal closure. In
      contrast, the COX-2 gene was expressed in the luminal epithelium and
      subepithelial stromal cells at the anti-mesometrial pole exclusively surrounding
      the blastocyst at the time of attachment reaction on day 4 and persisted through
      the morning of day 5. This uterine gene was not expressed at the sites of
      blastocyst apposition during progesterone (P(4))-treated delayed implantation,
      but was readily induced in the uterus surrounding the activated blastocysts after
      termination of the delay by estradiol-17beta (E(2)). The results suggest that PG
      synthesis catalyzed by COX-2 is important for localized increased uterine
      vascular permeability and attachment reaction. The COX-1 gene that was
      downregulated from the time of attachment reaction on day 4 was again expressed
      in the mesometrial and anti-mesometrial secondary decidual beds on days 7 and 8.
      These results suggest that PGs generated by COX-1 are involved in decidualization
      and/or continued localized endometrial vascular permeability observed during this
      period. In contrast, the COX-2 gene, expressed at the anti-mesometrial pole on
      days 4 and 5, switched its expression to the mesometrial pole from day 6 onward.
      These results suggest that PGs produced at this site by COX-2 are involved in
      angiogenesis for the establishment of placenta. In the ovariectomized mice, the
      COX-1 gene was induced in the epithelium by a combined treatment with P(4) and
      E(2). However, P(4) and/or E(2) treatments failed to influence the uterine COX-2
      gene. Overall, the results suggest that the uterine COX-1 gene is influenced by
      ovarian steroids, while the COX-2 gene is regulated by the implanting blastocyst
      during early pregnancy.

PMID- 9156515
TI  - Developmental and tissue-regulated expression of IGF-I and IGF-II mRNAs in Sparus
      aurata.
AB  - Recent studies have shown that homologues of the mammalian IGF-I and -II genes
      are also found in teleosts. We report here the cDNAs coding for IGF-I and IGF-II
      cloned from the gilthead seabream, Sparus aura ta. Sequence comparisons revealed
      that both IGFs have been well conserved among teleosts, although Sparus IGF-I is
      shorter bv three amino acid residues due to truncated B-and C-domains. Using the
      cloned cDNAs as probes, the relative expression of IGF-I and IGF-II mRNAs were
      assayed in different Sparus tissues. Sparus liver clearly contained the highest
      level of IGF-I mRNA while relatively high levels of IGF-II mRNA were found in
      liver, heart and gill using the ribonuclease protection assay. After GH
      administration the amount of IGF-I mRNA was increased by 220% in liver but no
      changes in IGF-II mRNA levels were detected in any tissue. We also assayed the
      expression of IGF-I and IGF-II in Sparus during early development. The IGF-II
      mRNA level was highest in larva I day after hatching and decreased thereafter. In
      contrast, IGF-I mRNA was detected in 1-day-old larva but there was an increase in
      expression in 12- and 16-day-old larva. These results demonstrated that the
      expression of IGF-I and IGF-II is highly regulated in teleosts and suggest that
      they play distinct roles during growth and development.

PMID- 9156516
TI  - The roles of adenosine 3',5'-cyclic monophosphate-dependent protein kinase A and
      protein kinase C in stimulus-secretion coupling in AtT-20 cells.
AB  - The ACTH-secreting mouse AtT-20/D16-16 anterior pituitary tumour cell line was
      used to study adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein
      kinase A (PKA) and protein kinase C (PKC) involvement in stimulus-secretion
      coupling pathways. In permeabilised AtT-20 cells under calcium ion-free
      conditions, forskolin (1O mu M), CRH-41 (1OOnM), guanosine 5'-O-(3
      thiotriphosphate) (GTP-gamma-S; 100 mu M) but not mastoparan (10 mu M) stimulated
      cAMP accumulation. Measurement of ACTH secretion under identical incubation
      conditions revealed that GTP-gamma-S and mastoparan significantly stimulated ACTH
      secretion but forskolin and CRH-41 did not. This dissociates cAMP accumulation
      from ACTH secretion under calcium ion-free conditions and indicated that the
      effects of mastoparan and GTP-gamma-S on ACTH secretion are not mediated by cAMP
      production. Calcium ions (1 nM to I mM) stimulated ACTH secretion from
      electrically permeabilised cells in a concentration-dependent manner. cAMP (100
      mu M) and phorbol 12-myristate 13-acetate (PMA; 100 nM) synergistically enhanced
      the response to calcium ions. cAMP did not stimulate ACTH secretion in the
      absence of calcium ions nor did it alter the concentrations at which calcium
      stimulated ACTH secretion. This suggests that stimulation of ACTH secretion via
      the calcium-dependent pathway is necessary before any cAMP-mediated enhancement
      of secretion is manifest. PMA, however, did stimulate ACTH secretion in the
      absence of calcium ions, indicating distinct mechanisms for PKC-evoked secretion.
      Co-incubation with cAMP and PMA did not exceed the secretory response obtained
      with the combination of PMA and calcium ions. CRH-41 (1 pM to 100 nM) and
      forskolin (1 nM to 100 mu M) stimulated ACTH secretion from intact cells in a
      concentration-dependent manner. Co-incubation with PMA (100 nM) further enhanced
      the ACTH response to CRH-41 and forskolin; the effects were simply additive. The
      present study indicates that there are distinct roles for PKA and PKC in stimulus
      secretion coupling in AtT-20 cells. The PKA-dependent pathway, acting in concert
      with the calcium messenger system, serves as part of the stimulus-secretion
      coupling pathway by which activation of CRH-41 receptors control ACTH secretion.
      The PKC-dependent pathway, in contrast, seems to be independent of the calcium
      messenger system and may represent a separate control mechanism of ACTH
      secretion.

PMID- 9156517
TI  - Insect cells infected with a recombinant baculovirus express both O- and N
      glycosylated forms of the rat glycoprotein hormone alpha-subunit.
AB  - Glycoprotein hormones LH, FSH, TSH and chorionic gonadotrophin are heterodimers
      composed of two non-covalently associated subunits, a common alpha- and a
      specific beta-subunit. A recombinant baculovirus containing a cDNA encoding the
      alpha-subunit of rat glycoprotein hormones was constructed. Viral-infected cells
      expressed, 48 h post infection, 7-10 mg immunoreactive alpha-glycopolypeptide/6 x
      10(8) cells, of which 65-6% was able to associate with native LH beta and formed
      a biologically active heterodimeric hormone that bound to testicular receptors.
      The treatment with specific glycanases showed that the recombinant alpha-subunit
      was produced as two differently glycosylated forms; an M(r) 23 000 form which
      contained exclusively N-linked carbohydrate units and another of M(r) 25 000
      which appeared to contain additional 0-linked carbohydrate. Data demonstrated
      that the alpha-subunit was expressed by insect cells in a manner similar to that
      by mammalian pituitary gonadotropes producing both the N- and O-glycosylated
      forms although only the N-glycosylated alpha-subunit is known to be capable of
      associating with the beta-subunit.

PMID- 9156518
TI  - The growth hormone-dependent decrease in hepatic fatty acid synthase mRNA is the
      result of a decrease in gene transcription.
AB  - The present study was conducted to determine the chronic effects of porcine
      growth hormone administration on fatty acid synthase (FAS) mRNA abundance and
      gene transcription in growing rats. Growth hormone treatment increased growth
      rate approximately 27% (P<0.01). Porcine growth hormone decreased FAS mRNA levels
      by 55%. The reduction in FAS mRNA was due to a marked decrease in transcription
      of the FAS gene (decreased by 80%). In contrast, porcine growth hormone did not
      affect mRNA abundance or transcription rate of another insulin-regulated gene,
      phosphoenolpyruvate carboxykinase. In summary, our results have established that
      chronic treatment with growth hormone decreases FAS mRNA by decreasing the
      transcription rate of the gene. Furthermore, they suggest that the effects of
      growth hormone are specific and are not mediated by general changes in insulin
      responsive gene expression in liver.

PMID- 9156519
TI  - Monoclonal antibodies to the human TSH receptor: epitope mapping and binding to
      the native receptor on the basolateral plasma membrane of thyroid follicular
      cells.
AB  - We have characterized four murine monoclonal antibodies (mAbs) to the
      extracellular domain of the human TSH receptor (TSH-R.E), the target autoantigen
      of Graves' disease. Recombinant TSH-R.E used as immunogen, was produced in E.
      coli as a fusion protein with glutathione-S-transferase or in a baculovirus
      insect cell system, as a non-fusion glycoprotein. To increase the epitope
      specificity of the mAbs, two different strains of mice (H-2(b) and H-2(d)) were
      immunized. The epitopes recognized by the mAbs were characterized by
      immunoblotting with various recombinant constructs of TSH-R.E and by binding to
      overlapping synthetic peptides of the receptor. The four IgG mAbs characterized
      recognized epitopes localized to different regions on the TSH-R.E; amino acids 22
      35 (A1O and A11, both IgG2b from H-2(b) animals), amino acids 402-415 (A7, IgG2b
      from H-2(b) animals) and amino acids 147-228 (A9, IgG1 from H-2(d) animals).
      Immunolocalization studies showed that mAb A9 recognized TSH-R.E on unfixed
      cryostat sections, where binding was localized to the basolateral plasma membrane
      of thyroid follicular cells, suggesting that this antibody reacts with the native
      receptor on thyroid cells. The binding of the mAbs A7, A10 and A11 was also
      restricted to the basal surface of thyroid cells, but only after acetone fixation
      of the sections, implying that the epitopes recognized on the amino and carboxyl
      terminus of the extracellular region of the receptor are not accessible on the
      native molecule. None of the mAbs stimulated cyclic AMP responses in COS-7 cells
      transiently transfected with full-length functioning TSH-R.E, whilst weak
      inhibition of binding of radiolabelled TSH to porcine membranes in a
      radioreceptor assay was apparent with mAb A10 and A11, but only at high
      concentrations of IgG. The ability of mAb A9 to bind to the native receptor
      without stimulating activity or inhibition of TSH binding suggests that antibody
      can bind to the central region of the TSH-R.E without perturbing receptor
      function. The availability of mAbs that recognize epitopes on different regions
      of the extracellular domain of TSH-R will lead to a better understanding of the
      autoantigenic regions on TSH-R implicated in disease activity.

PMID- 9156520
TI  - Molecular cloning of the cDNAs encoding pituitary glycoprotein hormone alpha- and
      gonadotropin II beta-subunits of the Japanese eel, Anguilla japonica, and
      increase in their mRNAs during ovarian development induced by injection of chum
      salmon pituitary homogenate.
AB  - cDNAs encoding the glycoprotein hormone alpha- and gonadotropin (GTH) II beta
      subunits of Japanese eel (Anguilla japonica) pituitary were cloned using the
      polymerase chain reaction. The nucleotide sequence of the glycoprotein hormone
      alpha-subunit cDNA was 364 base pairs (bp) long, encoding 117 amino acids, and
      that of the GTH II beta-subunit cDNA was 433 bp long, encoding 140 amino acids.
      The deduced amino acid sequence of each mature subunit showed high homology with
      those of other teleosts, indicating that the structure of GTH subunits has been
      conserved during the evolution of teleosts. Changes in the expression of these
      subunit genes during ovarian development induced artificially by the injection of
      chum salmon pituitary homogenate were examined using Northern blot analysis.
      Glycoprotein hormone alpha-subunit mRNA increased almost linearly during ovarian
      development, whereas GTH II beta-subunit mRNA was detected only at the late
      vitellogenic and migratory nucleus stages. These data indicate that eel GTH II is
      synthesized mainly at the late vitellogenic and migratory nucleus stages, and
      suggest that GTH II plays an important role in final oocyte maturation of
      Japanese eel. Changes in the expression of glycoprotein hormone alpha- and GTH II
      beta-subunits mRNA correlate with the serum estradiol-17 beta (E(2)) and
      testosterone profile during ovarian development. The increase in mRNA of both
      subunits is probably due to positive feedback of E(2) and testosterone produced
      by ovarian follicles in response to the GTH contained in chum salmon pituitary
      homogenate.

PMID- 9156521
TI  - Novel and sensitive detection systems for the vitamin D receptor--in situ-reverse
      transcriptase-polymerase chain reaction and immunogold cytochemistry.
AB  - The receptor for the active metabolite of vitamin D, 1,25(OH)(2)D(3), known as
      the vitamin D receptor (VDR), belongs to the steroid hormone nuclear receptor
      superfamily. We have developed novel methods for detection of VDR mRNA and
      protein within a human promyelomonocytic cell line, HL-60. Using the newly
      developed technique of in situ-reverse transcriptase-polymerase chain reaction
      (IS-RT-PCR), low levels of VDR mRNA could be amplified and demonstrated
      unequivocally within these cells, and also within a human kidney proximal tubule
      cell line, CL-8. Use of a novel immunogold cytochemical technique has allowed
      clear and sensitive detection of VDR protein expression within the HL-60 cells.
      Further development of IS-RT-PCR has allowed us to apply this technique to tissue
      sections. We have shown clear amplification of VDR transcripts within sections of
      formalin-fixed paraffin-embedded human kidney and liver. These techniques will be
      useful to localise specifically the VDR within cell types that contain low levels
      of mRNA and protein, and will permit further investigation of the role played by
      1,25(OH)(2)D(3) in cellular regulatory mechanisms.

PMID- 9156522
TI  - An alternative splice variant of the mouse TRH receptor mRNA is the major form
      expressed in the mouse pituitary gland.
AB  - The sequences of the mouse and rat TRH receptors (TRH-Rs) show 94% similarity at
      the protein level. However, they differ significantly at their carboxy terminals,
      i.e. the mouse TRH-R ends with an asparagine at position 393 while, in the rat,
      residue 393 is lysine and an additional 19 amino acids are added before the first
      stop codon. In the mouse cDNA, the sequence encoding these additional amino acids
      is located 224 bp downstream in the 3' untranslated region (3'UT). As the mouse
      TRH-R was cloned from thyrotrope-derived TtT97 tissue and the rat TRH-R from
      lactotrope-derived GH cell lines, we have investigated whether this difference at
      the carboxy terminus represents a species-specific or cell type-specific pattern
      of TRH-R expression. Total RNA was isolated from mouse pituitary and TtT97
      tissue, and rat pituitary and GH3 cells. Reverse transcription PCR analysis was
      performed using primers that would generate DNA fragments including the stop
      codon in either the mouse or the rat TRH-R and, in the mouse form, the extra 224
      bp of 3'UT. This would generate a product of 234 bp from the rat sequence and 441
      bp from the mouse sequence. In rat pituitary and GH3 cDNA, PCR generated the
      expected 234 bp product but not a band representing the mouse sequence. In both
      mouse pituitary and TtT97 cDNA, neither the expected 441 bp nor the 234 bp
      fragments were amplified; instead a larger, 829 bp, product was generated.
      Sequence analysis revealed a 388 bp insertion at position 1663 in the 3'UT
      compared with the published mouse TRH-R sequence. Ribonuclease protection
      analysis using this 829 bp fragment as a probe showed that this sequence
      represented the major TRH-R mRNA species in mouse pituitary and TtT97 RNA. A
      genomic clone containing this region of the mouse TRH-R gene was isolated and
      analysis of the sequence in this region revealed that this longer form of the
      mouse TRH-R could be generated by alternative splicing. In summary, we have shown
      that the carboxyterminal differences between the mouse and rat TRH-Rs are species
      specific rather than cell type-specific, and that the major TRH-R mRNA expressed
      in mouse pituitary contains an additional 388 bp of 3'UT compared with the
      published sequence. As a region in the 3'UT of the published mTRH-R sequence has
      been shown to be important for stability of this mRNA, this additional 3'UT
      sequence could have major effects on the regulation and stability of the mouse
      TRH-R mRNA.

PMID- 9156523
TI  - The human placenta expresses transcription enhancer factor-1 but there is no
      correlation with the expression of placental lactogen.
AB  - A transcriptional enhancer which has a consensus binding sequence for
      transcription enhancer factor-1 (TEF-1) has been found 3' of the hPL(3) gene. We
      examined whether TEF-1 is expressed by the human placenta and whether such
      expression is co-ordinated with that of human placental lactogen (hPL). Probing
      Northern blots of total RNA from first trimester and term placenta, the
      choriocarcinoma-derived cell line JAr and primary cultured cytotrophoblast cells
      with a cDNA for TEF-1 revealed transcripts of 12-13 kb and 3-4 kb. The level of
      TEF-1 expression was the same in first trimester as compared with term placenta
      and in undifferentiated JAr as compared with differentiated cytotrophoblast
      cells. hPL expression was tenfold higher in term compared with first trimester
      placenta and, whilst detectable in cytotrophoblast cells, was undetectable in JAr
      cells. These data show that TEF-1 is expressed by the placenta but is not co
      ordinated with hPL expression.

PMID- 9156524
TI  - Negative regulatory domains in a trophoblast interferon promoter.
AB  - A bovine trophoblast interferon (IFN-tau) gene promoter sequence (-450 to +26 bp
      relative to the transcription start site) led to expression of reporter gene
      (CAT) constructs transfected into L929 (murine fibroblast) or JAR (human
      choriocarcinoma) cells. Expression depended on the presence of an exogenous
      (SV40) enhancer. Poly(I)(C) activated endogenous IFN production in L929 and JAR
      cells but had no consistent effect on CAT expression. Similar results were
      obtained in L929 cells with inactivated Newcastle disease virus. There was no
      'priming' effect of exogenous Type I IFN. Deletion mutants revealed sites
      exerting negative control on expression between - 338 and - 247 bp, and between -
      150 and - 71 bp; these regions contained sequences resembling previously
      identified negative regulatory domains. In the absence of viral inducibility it
      is proposed that negative regulation contributes towards the stringent control of
      expression characteristic of IFN-tau genes.

PMID- 9156525
TI  - Proceedings of the Nordic Ciba Cancer Care Workshop on Advanced Breast Cancer.
      Stockholm, 18-19 January 1996.

PMID- 9156526
TI  - Neurodevelopmental profile of Down syndrome in Chinese children.
AB  - OBJECTIVE: To give an overall appraisal of the clinical features of Down syndrome
      (DS) in Chinese children with emphasis on the neurodevelopmental outcome, and to
      compare the related complications with that of other races. METHODOLOGY: The
      records of 124 Chinese children with DS assessed at the Child Assessment Centre
      of the University Department of Paediatrics in the Duchess of Kent Children's
      Hospital from 1985 to 1993 were reviewed. RESULTS: Thirty-one per cent of
      patients had microcephaly. Eighty-five percent (33/39) when assessed in the first
      year of life had a developmental quotient (DQ) above 50 but only 29% (2/7) had DQ
      above 50 when assessed after the age of 5. Only two patients (1.6%) had epilepsy:
      infantile spasms (1) and Lennox-Gastaut syndrome (1). Hearing impairment was
      found in 45% of children with mild conductive hearing impairment being the most
      common. CONCLUSIONS: Chinese children with DS, when compared with other races,
      were similarly intellectually disabled, but were less likely to develop epilepsy.

PMID- 9156527
TI  - Late-onset infections of infants in neonatal units.
AB  - OBJECTIVE: To examine regional variations in the incidence of late-onset neonatal
      infections in Australian and New Zealand neonatal units. METHODOLOGY: A
      longitudinal, prospective surveillance study of systemic sepsis (septicaemia or
      meningitis) in 11 neonatal units: 10 in the Australian States of the Northern
      Territory, New South Wales, Queensland, Victoria and Western Australia, and 1 in
      Christchurch, New Zealand. The results are reported of late-onset neonatal
      infection (defined as sepsis after 48 h) for the second year of prospective
      surveillance, data being collected from 1 October 1992 to 30 September 1993.
      RESULTS: Data were available on 24535 live births in Australia, representing
      approximately 10% of all live births in the country. There were 320 episodes of
      sepsis in Australian units affecting 294 babies. One hundred of these episodes
      (31%) were early-onset; 3.0% of babies admitted to six tertiary care neonatal
      units attached to maternity hospitals developed late sepsis, and this rate did
      not differ between units. The proportion of babies infected was inversely related
      to birthweight: 22.6% of babies under 1OOOg, but 0.6% over 2000g. Coagulase
      negative staphylococci were the commonest cause of late-onset sepsis. There were
      26 episodes of S. aureus septicaemia, of which only one was due to MRSA.
      Meningitis occurred in 13 babies (5.9%) with late-onset sepsis. The mortality
      from late-onset sepsis was 7.7%. CONCLUSIONS: Coagulase-negative staphylococci
      are the commonest cause of late-onset sepsis of babies in neonatal units. There
      were no major regional differences in the incidence of, or the organisms causing,
      late sepsis.

PMID- 9156528
TI  - Visits to medical practitioners in the first 6 months of life.
AB  - OBJECTIVE: To assess the use of medical practitioners' services by mothers and
      their babies in the 6 months following childbirth. METHODOLOGY: Aggregated
      Medicare data detailing medical practitioner services provided to a random sample
      of 650 Victorian babies born between 1 March and 31 May 1993 and their mothers
      were obtained from the Health Insurance Commission. This provided data on
      services provided between March and December of 1993 to the selected cohort.
      Services provided by the public hospital system to mothers and babies are not
      included. RESULTS: Mothers and babies in the sample used 6404 medical
      practitioner services in the 6 months following birth; 57% of services were to
      babies, 43% to mothers. Of the 6404 medical practitioner services 5042(79%) were
      provided by general practitioners (GP), 804(12%) by paediatricians, 319(5%) by
      obstetricians and 239(4%) by 'other' specialists. The mean number of visits to a
      GP by mothers was 3.5 and by babies was 4.2 in the 6 months following birth.
      General practitioners were more likely to be vocationally registered and there
      were differences in the item numbers charged between those who were vocationally
      registered and those who were not. The length of GP consultation differed
      significantly between mothers' and babies' visits. CONCLUSIONS: A previously
      undocumented level of postnatal use of medical practitioner services is
      presented. It suggests a significant level of postnatal maternal and infant
      morbidity that requires further study.

PMID- 9156529
TI  - Surgery and the tiny baby: sensorineural outcome at 5 years of age. The Victorian
      Infant Collaborative Study Group.
AB  - OBJECTIVE: To determine whether an association exists between long-term
      sensorineural outcome and the need for surgery requiring general anaesthesia
      during the primary hospitalization in extremely preterm (<27 weeks of gestational
      age) or extremely low birthweight (ELBW birthweight <100Og) infants. METHODOLOGY:
      A geographically determined cohort study of extremely preterm or ELBW children in
      the State of Victoria, Australia. The study subjects were consecutive survivors
      with either gestational ages <27 weeks or birthweights <10OOg born in the State
      of Victoria during 3 years from 1 January 1985. The main outcome measure was the
      rate of sensorineural disability at 5 or more years of age in relation to
      surgical procedures requiring general anaesthesia performed during the primary
      hospitalization. RESULTS: Of 221 children surviving to 5 years of age, 54 (24.4%)
      had at least one surgical operation requiring general anaesthesia during their
      primary hospitalization. The operations included the following: (i) ligation of
      ductus arteriosus (n = 26); (ii) inguinal hernia repair (n = 16); (iii) central
      nervous system surgery (n = 4); (iv) gastrointestinal surgery (n = 5); and (v)
      tracheostomy or bronchoscopy (n = 5). Of the 221 survivors to 5 years of age, 218
      (98.6%) were assessed for sensorineural impairments and disabilities. Of the 53
      children who were assessed at 5 or more years of age and who had had surgery, 7
      (13.2%) were severely disabled, 8 (15.1%) were moderately disabled, 12 (22.6%)
      were mildly disabled,and 26 (49.1%) were non-disabled. The overall rate of
      sensorineural disability was significantly higher in children who had been
      operated on compared with those who had not (Mann-Whitney U-test, z =3.7,
      P<0.001). CONCLUSIONS: There is an adverse association between the need for
      surgery requiring general anaesthesia during the primary hospitalization and
      sensorineural outcome in extremely preterm or ELBW infants.

PMID- 9156530
TI  - Early post-traumatic seizures in children: clinical and radiological aspects of
      injury.
AB  - OBJECTIVE: To determine the type and outcome of early post-traumatic seizures in
      children and the factors associated with it. METHODOLOGY: A prospective
      observational study on all consecutive children with head injuries at the General
      Hospital Kuala Lumpur between November 1993 and December 1994. The onset, type
      and frequency of seizures occurring within the first week of injury were
      documented. Using inpatients as a cohort, logistic regression analysis was used
      to determine clinical and radiological variables significantly associated with
      seizures. The outcome 6 months post-injury was assessed using the Glasgow Outcome
      Scale. RESULTS: Fifty-three of 966 children (5.5%) developed seizures within the
      first week of trauma. Seven (13.2%) occurred within 1 h of injury, 30 (56.6%)
      between 1 and 24 h and 16 (30.2%) after 24 h. Factors significantly associated
      with early post-traumatic seizures were female sex, age less than 2 years, loss
      of consciousness for more than 24h and acute subdural haematoma (P<0.01).
      Children with seizures had a poorer outcome (death or severe disability) than
      inpatients without seizures (21/53 vs 19/182, P<0.001). The outcome was worst in
      children with recurrent partial seizures, who had a longer injury-seizure
      interval and were more likely to have focal neurologic deficits compared to those
      with sporadic or generalized seizures. CONCLUSIONS: Anticonvulsant prophylaxis to
      minimize the adverse effects of early seizures in head injury should be
      considered for young children (less than 2 years old) with subdural haematoma and
      a prolonged duration of coma. Prompt and effective control of recurrent seizures
      is recommended.

PMID- 9156531
TI  - Haemodynamic effects of differing blood transfusion rates in infants less than
      1500 g.
AB  - OBJECTIVE: To investigate whether the haemodynamic effects of the standard 2-3 h
      blood transfusion increases the risk for intraventricular haemorrhage (IVH) and
      patent ductus arteriosus (PDA) in very low birthweight infants. METHODOLOGY: In a
      randomized controlled study, haemodynamic changes using slow and rapid
      transfusion were compared. Twenty-seven very low birthweight infants were divided
      between 12h (n = 14) and 3h (n = 13) transfusion groups. Blood pressure, ejection
      fraction (EF), anterior cerebral artery pulsatility index (PI), blood gases,
      serum electrolytes and haematocrit were measured pre- and post-transfusion.
      Infectious status was also monitored. RESULTS: Blood pressure (48.1/25.5 vs
      55.7/30.2 mmHg) and EF (0.68 vs 0.73) increased significantly during rapid
      transfusion (P<0.01) but remained stable with slow transfusion. Serum potassium,
      base excess and incidence of infection did not increase in either group.
      CONCLUSIONS: Slow transfusion causes less haemodynamic disturbance than rapid
      transfusion, thereby preventing the potential risk for IVH and PDA.

PMID- 9156533
TI  - Lethal kyphomelic dysplasia.
AB  - A lethal form of kyphomelic dysplasia with severe bowing of the long bones of the
      lower extremities is reported.

PMID- 9156532
TI  - Childhood asthma complicated by anxiety: an application of cognitive behavioural
      therapy.
AB  - OBJECTIVE: To identify characteristics within the patient and the environment
      that might be instrumental in triggering and maintaining an episode of asthma in
      children whose objective lung function tests suggested a less severe exacerbation
      than the subjective report and behaviour indicated, and also to investigate the
      efficacy of a cognitive behavioural intervention, using the paradigm of a panic
      anxiety disorder. METHODOLOGY: A retrospective investigation of 23 case records
      and psychosocial histories, focusing on the characteristics of the sample and the
      number of presentations and admissions before and after the intervention, which
      is described. RESULTS: Children aged 10-12 years predominated. A precipitating
      event triggered a fear that their condition had deteriorated in the context of a
      growing understanding that asthma in a child could be fatal. A reduction in
      presentations and admissions post-intervention is shown. CONCLUSIONS: The
      paradigm of panic disorder is useful to understand the sudden onset of apparent
      deterioration in the severity of asthma when objective lung function tests do not
      support the subjective experience.

PMID- 9156534
TI  - Congenital dyserythropoietic anaemia: report of three cases.
AB  - Between January 1985 and June 1992, the Paediatric Department of Hospital
      Universiti Sains Malaysia has diagnosed congenital dyserythropoietic anaemia in
      three children, two of whom were siblings. The age of onset ranged from 1 to 3
      years. All of them became transfusion-dependent before the age of 4 months. One
      of them was successfully treated with bone marrow transplantation.

PMID- 9156535
TI  - Cannabis cookies: a cause of coma.
AB  - Despite the prevalence of cannabis use in the community, reports of adverse
      effects in young children are rare. Two cases of cannabis-induced coma are
      reported following accidental ingestion of cannabis cookies. The possibility of
      cannabis ingestion should be considered in cases of unexplained coma in a
      previously well young child if signs of conjunctival hyperaemia, pupillary
      dilatation and tachycardia are present and other causes such as CNS infection or
      trauma are unlikely. Specific screening for cannabinoids should be undertaken.

PMID- 9156536
TI  - Monitoring the effects of prednisone in Duchenne dystrophy.

PMID- 9156537
TI  - Transient hyperphosphatasaemia and malabsorption syndrome.

PMID- 9156538
TI  - Determination of copper and zinc levels in human hair: influence of sex, age, and
      hair pigmentation.
AB  - The Cu and Zn levels of both 607 men (1-85 y old) and 649 women (1-92 y old) were
      determined by atomic absorption spectrometry. Sex does not influence Cu (14.89 +
      or - 0.89 mu g/g and 15.26 + or - 0.79 mu g/g hair for males and females,
      respectively) and Zn contents (200.97 + or - 9.68 mu g/g for men and 209.81 + or 
      9.49 mu g/g hair for women). Age influences Cu and Zn concentrations, but only
      significantly in females: Cu levels decrease over 60 y of age; whereas Zn levels
      increase significantly from age groups 2-5 to 20-40 years. Hair color influences
      Cu concentrations in both males and females. In males, white hair contains less
      Cu than black hair; in females, white hair's Cu levels are significantly lower
      than those of dark blond, red, light brown, and brown hair. There are no
      significant differences in Zn concentrations with respect to different hair
      colors, in either males or females.

PMID- 9156539
TI  - Urinary selenium in healthy and diabetic Saudi Arabians.
AB  - We examined Se in urine of 170 Saudi Arabian diabetics (19 insulin-dependent
      [type 1] and 151 insulin-independent [type 2]) and in an equal number of control
      subjects of the same origin by measuring the ratio of the concentration of this
      metal (C(Se)) to that of creatinine in urine (C(creat)) for each subject. The
      mean (and SEM) of C(Se) /C(creat) for the control subjects was 56 (2.9) mu
      mol/mol creat, whereas, the value for the diabetics combined or separated into
      type 1 and type 2 was 56.7 (3.2), 51.5 (6.3), and 57.4 (3.5) mu mol/mol creat,
      respectively. With the exception of type 2 diabetics who were treated with
      insulin in addition to oral hypoglycemic and diet (35 patients) (mean [SEM] = 43
      (4.3) mu mol/mol creat), there was no significant difference in C(Se)/C(creat)
      between the diabetics and control subjects. Also, there was no significant
      correlation between C(Se)/C(creat) and age, sex, or weight of diabetics, whereas,
      the correlation with the degree of diabetic control was significant (p < 0.0136).
      Of all diabetes-associated disorders (cardiovascular diseases, neuropathy,
      ophthalmologic diseases, infections, and hepatic disease), only ophthalmologic
      diseases appears to cause a significant (p < 0.05) reduction in C(Se)/C(creat),
      but only among type 2 diabetics. Inasmuch as Se status is reflected by urinary
      Se, healthy Saudi Arabians appear to have Se status that is comparable or higher
      than those reported for other populations.

PMID- 9156541
TI  - Research in school settings.

PMID- 9156540
TI  - Biological evaluation of trace element data in human ovaries by statistical
      analysis.
AB  - Analysis of variance, analysis of covariance, correlation coefficient, multiple
      correlation, and partial correlation coefficient statistical tests were applied
      to Cs, Cr, Co, Fe, Rb, Sc, Se, and Zn content in human ovaries in order to
      evaluate statistically the possible relationships between these trace elements
      at: the ovary as an organ, each ovarian phase separately, each morphological part
      independent of the ovarian phase, and between cortex and medulla within the
      ovarian phases. The element Cs seems to have a homogeneous distribution between
      cortex and medulla within reproductive and menopausal phase. Zinc shows a trend
      to have an antagonistic relation with Cs, Cr, Co, and Fe during fetal and
      reproductive phases and not during menopausal phase. The relationship between Zn
      and Cs when Fe is kept constant could be used as a tool for the decontamination
      of the ovary from an abnormal Cs content or for the inhibition of the
      accumulation of the same element to the ovarian tissue.

PMID- 9156542
TI  - Abnormalities in weight status, eating attitudes, and eating behaviors among
      urban high school students: correlations with self-esteem and anxiety.
AB  - PURPOSE: The study's objective was to determine the prevalence of abnormalities
      in weight, eating attitudes, and eating behaviors among an urban teenage
      population. METHODS: Measures of weight, height, and blood pressure were obtained
      from 1,001 students attending regularly scheduled physical education classes in a
      New York City high school the population of which was 66% black and 23% Hispanic.
      The mean age was 16 years old; 55% were female and 45% were male. Approximately
      three quarters of the students completed the Eating Attitudes Test (EAT-26),
      Rosenberg Self-Esteem Scale, Spielberger Trait Anxiety Inventory, and a
      questionnaire on eating behaviors. RESULTS: By percent ideal body weight (%IBW),
      25% of students were obese (>20% above IBW), 18% were overweight, and 5% were
      underweight. Abnormal EAT scores (>21), were found in 6% of males and 15% of
      females. Students reported that they had engaged in the following nutritional
      behaviors at least three times in the past week: eating candy (59%), skipping
      breakfast (58%), skipping lunch (42%), eating fast foods (28%), and skipping
      dinner (14%). Self-esteem was high in 60%, medium in 21%, and low in 19%. Mean
      self-esteem was significantly higher (P < .0001) than established norms. Self
      esteem and anxiety were inversely correlated (r = .40, P < .001), and low self
      esteem and high anxiety were both associated with high EAT scores (r = .29, P <
      .001). Self-esteem and anxiety of obese students did not differ from those who
      were of normal weight. CONCLUSIONS: Among this population of urban high school
      students there were: (a) a large number of overweight adolescents; (b) a
      significant subgroup with eating attitudes suggestive of an eating disorder; and
      (c) high levels of self-esteem and normal levels of anxiety, which were
      independent of weight status.

PMID- 9156543
TI  - Violence and mental health problems among urban high school students.
AB  - PURPOSE: We sought to determine the extent of exposure to violence and its
      relationship to other mental health risks among an urban teenage population.
      METHODS: Students attending regularly scheduled physical education classes
      completed a Violence Survey, a Suicidal Ideation Survey, the Depression Self
      Rating Scale (DSRS), and the Adolescent Alcohol Involvement Scale. Of the 630
      students who completed the anonymous assessment 45% were male, 55% female, 61%
      black, 30% Hispanic; 54% grades 9-10, and 46% grades 11-12. RESULTS: Half of the
      students reported knowing someone who had been murdered, 61% indicated they had
      witnessed a robbery, 59% had witnessed a beating, 37% had witnessed a shooting,
      and 31% had witnessed a stabbing. Mental health problems reported by these
      students included: depression (DSRS score > 13) in 31%, suicidal ideation in 16%,
      suicide attempts in 10%, drinking > 1 x per month in 21%, and drinking daily in
      5%. Univariate analysis revealed that students who witnessed a shooting or
      stabbing were more likely (p < .05) to be both male and black. Multivariate
      analysis revealed that students reporting knowing someone who was murdered were
      twice as likely to report suicidal ideation and four times as likely to report
      suicide attempts. Witnessing a stabbing was associated with twice the likelihood
      of reporting suicide ideation and three times the likelihood of reporting suicide
      attempts. Witnessing a shooting was associated with twice the likelihood of
      alcohol use. Witnessing a beating or robbery had no significant relationship to
      measured variables. CONCLUSIONS: Among this population of urban teenagers there
      are many who have witnessed violence and a subgroup who have witnessed shootings
      and stabbings and are at increased risk for mental health problems. A
      comprehensive medical and psychosocial history should include a violence
      assessment for all urban teens.

PMID- 9156544
TI  - AIDS knowledge, concerns, and behavioral changes among inner-city high school
      students.
AB  - Knowledge of AIDS, attitudes toward AIDS and condoms, and behavioral changes
      because of AIDS were studied in 771 students, Grades 9-12 (mean age, 16 years)
      who completed anonymous questionnaires in gym classes of a New York City high
      school. Students demonstrated good knowledge of AIDS, with some misconceptions,
      and significant concerns about AIDS, with some behavioral changes, but most
      continued to engage in high-risk behaviors. These data indicate that efforts
      aimed at HIV/AIDS prevention in adolescents must translate knowledge and concerns
      into behavioral change.

PMID- 9156545
TI  - Sports participation in an urban high school: academic and psychologic
      correlates.
AB  - PURPOSE: To study positive and negative correlates of sports participation in
      inner-city youth. METHODS: We distributed anonymous questionnaires to 838
      students in gym classes of an urban New York City High School. Forty five percent
      of students were male and 55% female, with mean age 16.0 years; 64% in grades 9
      10, and 36% in grades 11-12; 63% black, 27% Hispanic, and 10% other; and 30% A/B
      students, 38% C students, and 32% D/F students. RESULTS: All students reported
      some involvement in sports: 37% in 1-2 sports, 29% in 3-4 sports 24% in > or = 5
      sports; 20% played on local teams, and 12% on junior or senior varsity.
      Approximately one-third each reported no weekday sports participation (30%), 1-2
      hours per day (34%), or > or = 3 hours (36%); and 34% reported no participation
      on weekends, 26% reported 1-2 hours per day, and 40% > or = 3 hours. Basketball,
      volleyball, baseball, and weight lifting were the most common sports. Enjoyment,
      recreation, and competition were the most commonly reported reasons for
      participation. While 86% of subjects considered school "extremely" or "very"
      important, 35% considered sports "extremely" or "very" important. However, many
      believed they would "definitely" or "probably" receive an athletic scholarship
      (52% males, 20% females). Males reported more (p < .05) weekday, weekend, and
      team participation, and greater expectations (p <.001) of a future in sports.
      Sports involvement was not statistically associated with academic performance or
      scores on either the Rosenberg Self-Esteem Scale or Depression Self Rating Scale.
      Steroid use, at least once, was reported by 11% of males and 4% of females.
      Thirteen percent of students (21% males, 6% females) tried to gain weight for
      sports and 20% of both males and females tried to lose. Sports injuries within
      the past year were reported by 15% of students, and approximately three-quarters
      could correctly answer each of five questions about basic first aid. CONCLUSIONS:
      The data indicate that most of these urban youth had athletic involvement, many
      had unrealistic expectations for their futures, and some utilized unhealthy
      behaviors in an attempt to enhance performance. Among these students, no
      association was found between sports involvement and academic performance, self
      esteem, or depression.

PMID- 9156546
TI  - Do school-based health centers improve adolescents' access to health care, health
      status, and risk-taking behavior?
AB  - PURPOSE: The purpose of this investigation was to assess the School-Based
      Adolescent Health Care Program, which provided comprehensive health-related
      services in 24 school-based health centers. METHODS: The outcomes evaluation
      compared a cohort of students attending 19 participating schools and a national
      sample of urban youths, using logit models to control for observed differences
      between the two groups of youths. Outcome measures included self-reports
      concerning health center utilization, use of other health care providers,
      knowledge of key health facts, substance use, sexual activity, contraceptive use,
      pregnancies and births, and health status. RESULTS: The health centers increased
      students' access to health care and improved their health knowledge. However, the
      estimated impacts on health status and risky behaviors were inconsistent, and
      most were small and not statistically significant. CONCLUSIONS: School-based
      health centers can increase students' health knowledge and access to health
      related services, but more intensive or different services are needed if they are
      to significantly reduce risk-taking behaviors.

PMID- 9156547
TI  - Characteristics of users and nonusers of health clinics in inner-city junior high
      schools.
AB  - PURPOSE: To compare the demographic, behavioral, psychosocial, and academic
      characteristics of users versus nonusers of inner-city junior high school-based
      health clinics. METHODS: Students who used (n = 1344) and did not use (n = 2394)
      the health clinics based in four junior high schools in an economically
      disadvantaged, medically underserved New York City school district were compared
      on their responses to a health risk survey administered at the end of the 1991/92
      academic year. RESULTS: Compared to students who did not use the clinics,
      students who used the clinics were more likely to have had unprotected sexual
      intercourse, to have had suicide intentions or attempts, to be suspended from
      school for fighting, to be exposed to violence and the illicit drug culture, to
      hold beliefs favoring involvement in sexual intercourse and suicidality, and to
      have failed subjects in school. CONCLUSIONS: Users of these junior high school
      based health clinics are engaging in behaviors and hold beliefs that place them
      at risk for serious adverse health outcomes. School-based clinics have the
      potential to provide early intervention for these high risk adolescents.

PMID- 9156548
TI  - Student attitudes toward school-based health centers.
AB  - PURPOSE: Little is known about student attitudes toward school-based health
      centers (SBHCs) or about factors that influence SBHC enrollment. METHODS:
      Students in 9 Baltimore schools with SBHCs and 4 schools without health centers
      were surveyed in May 1991, using an anonymous classroom questionnaire. SBHC
      enrollees, nonenrollees from health center schools, and students in schools
      without health centers were compared using bi-variate analyses. Logistic
      regression analyses identified predictors of enrollment. RESULTS: A total of 91%
      of enrollees supported having a SBHC compared with 89% of nonenrollees and 77% of
      students from non-health center schools (p < .001). Support for a variety of
      services (including contraceptive services) was significantly higher among
      enrollees and nonenrollees compared with students in non-SBHC schools. A total of
      86% of enrollees rated the quality of care "satisfactory" to "excellent" and 79%
      rated privacy in the school health center as "satisfactory" to "excellent." The
      most common reason given for not enrolling was satisfaction with current
      provider. Independent predictors of student confidence in the privacy of SBHCs
      included prior SBHC use and enrollment of close peers. Predictors of enrollment
      included: one or more self-reported health problems; having medical assistance;
      attending one or more special education classes; enrollment of close peers;
      membership in a school club, sports team, or church organization; and being
      African-American. CONCLUSIONS: Students overwhelmingly supported school-based
      health centers. Personal experience and peer influences were important in shaping
      student attitudes. We found evidence of a "learning curve" gradient in student
      attitudes such that students with the greatest exposure to SBHCs (as measured by
      attending a SBHC school, enrolling in the SBHC, and using the health center) had
      the most favorable attitudes.

PMID- 9156549
TI  - School health centers and primary care for adolescents: a review of the
      literature.

PMID- 9156550
TI  - Society for Adolescent Medicine 1997 meeting.

PMID- 9156551
TI  - [Integral kinetics of multisubstrate enzyme reactions. Criteria of kinetic
      behavior and characteristic coordinates for solution of direct and reverse
      problems].
AB  - General schemes of unbranched multisubstrate enzyme reactions associated with
      enzyme inactivation during catalysis are analyzed. Equations of integral kinetics
      at constant substrate concentrations and at depletion in one of the substrate are
      presented. Experimental dose-response curve characterized by additivity of some
      enzyme intermediates (absorption spectra, fluorescence, EPR, etc.) are
      theoretically analyzed. Also rapid equilibrium at certain stages of enzyme
      reaction is considered. The interrelationship of enzyme intermediates is a
      criterion of the kinetic behavior of enzyme reaction mechanism. New coordinates
      are suggested for the analysis of the integral kinetics of self-inactivating
      enzymes. Results of the analysis are used for interpretation of the data on
      arachidonic cascade enzymes.

PMID- 9156552
TI  - [Silver staining of proteins separated by polyacrylamide gel electrophoresis:
      mathematical model].
AB  - Silver staining of proteins separated by electrophoresis in the thin layer of
      polyacrylamide gel can be quantitatively measured when the results are
      statistically treated. In the mathematical model, the reduction of protein-bound
      silver ions (crucial silver staining step) is considered to be autocatalytic.
      According to the model, the reaction rate strongly depends on the stability
      constant of silver complexes with functional groups of protein amino acids; and
      the shape of the calibration curve is determined by the ratio of concentration of
      silver-binding side chain groups to the reciprocal value of the stability
      constant. The complex shape of the curves can be explained the combination of
      autocatalysis and saturation. High sensitivity of this reaction to experimental
      conditions, contribution of complexes with different stability constants to the
      intensity of protein band staining, and optical effects are analyzed.

PMID- 9156553
TI  - [A method of calculation of accessibility to solvent of aromatic amino acid
      residues of proteins in water-organic mixtures].
AB  - Suggested method for calculation of solvent accessibility of tryptophan and
      tyrosine residues in water-organic mixtures is based on evaluation of second
      order derivatives of UV spectra. Second order derivative of the spectrum enable
      differentiation between direct effects of the organic solvent on spectral
      characteristics of exposed aromatic amino acid residues and the effect of the
      organic solvent on protein conformation. The method is suitable for calculation
      of exposition of tryptophan in water-organic mixtures if the content of tyrosine
      amino acid residues in protein does not exceed the content of tryptophan. Similar
      method of calculation of exposition of tyrosine residues can be used in proteins
      when the content of tyrosine is at least 5-fold higher than the content of
      tryptophan. For example, solvent accessibility of tryptophan residues of
      chymotrypsin is calculated in the presence of various organic solvents including
      ethanol, dioxane, and dimethyl formamide.

PMID- 9156554
TI  - [Selective chemical modification of cytochrome P450scc (CYP11A1) with
      diiodofluorescein iodoacetamide in the study of the role and topology of
      interdomain hinge of the hemoprotein molecule].
AB  - Bovine adrenocortical cytochrome P450scc (CYP11A1) was selectively modified with
      diiodofluorescein iodoacetamide (DIFIA). Only Cys264 is labeled in the P450
      polypeptide chain. The modification significantly affected the cholesterol
      hydroxylating activity in the reconstituted system containing NADPH, adrenodoxin
      reductase, adrenodoxin, and soluble or membrane-bound P450scc. The inhibitory
      effect correlates with decreased affinity of cytochrome P450scc to intermediate
      electron carrier, adrenodoxin. Cytochrome P450scc is modified in liposomes and
      the modified membrane-bound protein is cleaved by trypsin forming two large
      fragments F1 and F2 corresponding to the N- and C-terminal regions of the
      molecule. The data indicate that the Cys264-containing region of the cytochrome
      P450scc molecule is exposed to the surface of protein globule, located outside of
      the membrane, and can participate in protein-protein interactions.

PMID- 9156555
TI  - [Modulation of melittin-induced hemolysis of erythrocytes].
AB  - Three main groups of chemicals influence melittin-induced hemolysis including
      neutral compounds and inhibitors and activators of hemolysis. Inhibitors include
      divalent cations Zn2+ and Ca2+, albumin, DIDS, etc.; their potency significantly
      increases if they are present at early stages of peptide-membrane interaction.
      The rate of melittin-induced hemolysis depends on time of preincubation with the
      cells in physiologic saline but does not depend on the presence of inhibitors or
      activators. Longer incubation increases the rate of hemolysis. These effects can
      be due to membrane inhibitory components with specific affinity to melittin which
      initially protect the membrane from its lytic effect; these components can
      dissociate from the cell surface after dilution and incubation in physiologic
      saline. According to the suggested model, characteristics of peptide-induced
      hemolysis of erythrocytes are determined by sequential stages of peptide-membrane
      interaction and depend on the formation of triple non-lytic complex comprising
      the membrane inhibitory component, the blocker, and the peptide; the complex
      inhibits destruction of the membrane.

PMID- 9156556
TI  - [Inhibition of ADP-induced platelet aggregation by guanidine thiols--a novel
      class of guanylate cyclase activators and NO-synthase substrates].
AB  - Antiaggregatory properties of guanidine thiol derivatives and their effect on
      human platelet guanylate cyclase activity were studied. The molecules of
      guanidine thiols contain guanidine and thiol groups which are the donor and
      acceptor of nitric oxide (NO), respectively. Three synthetic guanidine thiol
      derivatives were studied including mercaptoethylguanidine (MEG),
      mercaptoethylguanidine disulfide (MEG-disulfide), and mercaptoethylguanidine
      methylated at SH-group (S-methylmercaptoethylguanidine (S-methyl MEG)). All
      compounds are the substrates of NO-synthase and activators of human platelet
      guanylate cyclase. The stimulatory effects of MEG and MEG-disulfide on guanylate
      cyclase activity were 2- and 4-fold higher, respectively, than the effect of L
      arginine. Stimulation of the enzyme by S-methyl MEG is similar to L-arginine.
      Antiaggregatory properties of these compounds correspond to the extent of
      guanylate cyclase activation. Extent of guanylate cyclase activation (S-methyl
      MEG < MEG < MEG-disulfide) significantly correlates with inhibition of ADP
      induced platelet aggregation and with acceleration of spontaneous disaggregation
      of platelets. The mechanism of directed enhancement of antiaggregatory properties
      of the compounds can depend on their chemical structure and extent of guanylate
      cyclase activation.

PMID- 9156557
TI  - [Site-specific endonuclease BspR7I from thermophilic strain of Bacillus sp. R7].
AB  - A site-specific endonuclease which recognizes the sequence 5'-CCTNAGG-3' was
      purified to homogeneity from the thermophilic strain Bacillus sp. R7. The
      endonuclease (BspR7I) is monomeric protein with an apparent molecular weight of
      37 kD. The enzyme is active over a wide range of NaCl concentrations, pH, and
      temperatures. BspR7I cleaves DNA substrates according to the scheme: 5'-CC
      decreases TNAGG-3' 3'-GGANT increases CC-5', hence the endonuclease represents an
      isoschizomer of Bsu361.

PMID- 9156558
TI  - [The major cytoplasmic mRNP protein, p50, is required for efficient mRNA
      translation in vitro].
AB  - The major cytoplasmic mRNP protein of somatic cells, p50, is the member of the Y
      box-binding transcription factor family and can control gene expression at two
      levels including mRNA transcription and translation. It has been demonstrated
      that p50 is responsible for the inactive state of mRNA within free mRNPs. In this
      work, we show that the Y-box-containing DNA (Y-DNA) predominantly binds to p50 in
      rabbit reticulocyte lysates and causes translation inhibition of the endogenous
      and exogenous globin mRNA and prokaryotic beta-galactosidase mRNA. Preincubation
      of Y-DNA with purified p50 prevents the inhibition. Inhibition of protein
      biosynthesis by the Y-DNA is not due to the degradation or functional
      inactivation of mRNA. The inhibition is associated with the decay of
      polyribosomes and dissociation of a newly synthesized protein from the ribosomes.
      The data indicate that Y-DNA inhibits protein biosynthesis predominantly at the
      initiation stage and that p50 is an essential component of the translation
      initiation apparatus.

PMID- 9156559
TI  - Abnormal cholinesterase activity: understanding and interpretation.
AB  - Abnormal acetylcholinesterase and cholinesterase activity may occur due to a)
      various physiological and pathological conditions, b) genetic factors or c)
      interaction with drugs and cholinesterase inhibitors. This paper reviews and
      discusses such conditions in which both cholinesterases show abnormal activity
      focusing on better understanding and interpretation of laboratory results. In
      particular, the mechanism of interaction of both cholinesterases with their
      inhibitors such as organophosphorus and carbamate compounds is discussed. Some
      practical recommendations concerning sampling and preparation of samples for
      enzyme assay are given in order to avoid errors that may affect laboratory
      findings.

PMID- 9156560
TI  - Simplified sizing of low-density lipoprotein using polyacrylamide gradient gel
      electrophoresis of plasma.
AB  - Low-density lipoprotein (LDL) particles can be separated into subfractions
      according to size by non-denaturing polyacrylamide gradient gel electrophoresis.
      Established research methods require specialised equipment and are frequently
      unsuited to the clinical laboratory. In this study, we utilised a colour flat bed
      scanner in conjunction with shareware image analysis software to compare LDL
      particle diameters of isolated LDL with LDL in whole plasma. LDL was isolated by
      ultracentrifugation and electrophoresed on 3-13% gels (Gradipore; Sydney,
      Australia) for 2400 Volt-hours in parallel with plasma and molecular size
      standards. Coomassie Blue-stained gels were scanned in reflexive mode using a
      colour flat-bed scanner and Adobe Photoshop 3.0 software. Density traces of each
      lane were obtained using NIH Image software (public domain, USA). LDL particle
      diameters were determined from calibration curves of the log of molecular
      diameter of standards against migration distance. There was a good correlation
      between LDL particle diameters obtained using isolated LDL and whole plasma (r =
      0.87, P < 0.001; n = 22). However, the group means (+/- S.D.) (24.7 +/- 0.6 and
      24.8 +/- 0.5 nm respectively) were statistically different on the paired t-test
      (P < 0.05). It is unclear whether this numerically small difference is due to
      alterations in LDL during the longer preparative procedures for LDL, or to matrix
      effects during electrophoresis of plasma samples. In conclusion, plasma samples
      stained with Coomassie Blue and scanned with a colour flat bed scanner can
      conveniently be used for LDL particle sizing by non-denaturing polyacrylamide
      gradient gel electrophoresis.

PMID- 9156561
TI  - Urinary biotinidase and alanine excretion in patients with insulin-dependent
      diabetes mellitus.
AB  - Twenty-four-hour urine specimens from 21 juvenile insulin-dependent diabetics and
      10 healthy controls were compared with respect to biotinidase activity and
      alanine content. Urinary biotinidase activity was analysed by a newly developed
      high-performance liquid chromatography (HPLC) method. It was found that the
      excretion of biotinidase in urine was elevated in diabetics (7.02 mU/d; p <
      0.005) as compared with controls (not detectable). Alanine excretion was also
      found to increase (p < 0.01) in diabetics. Biotinidase excretion in diabetics was
      correlated with alanine excretion (rS = 0.667; p < 0.01), but not with protein,
      albumin or N-acetyl-beta-glucosaminidase excretion. The simultaneous elevation of
      urinary biotinidase and alanine excretion in juvenile diabetics suggests that
      changes in kidney metabolism arise in the early stages of diabetes.

PMID- 9156562
TI  - Marginal folate deficiency as a possible cause of hyperhomocystinaemia in stroke
      patients.
AB  - It has been reported that patients with vascular disease seem to increase their
      concentration of plasma homocysteine after the acute episode, whereas reexamined
      control subjects do not change their concentration of plasma homocysteine over
      time. Since the main determinants of plasma homocysteine are serum cobalamin,
      blood folate and serum creatinine we measured these quantities in 20 control
      subjects and 49 stroke patients in the acute phase and at reexamination 1.5-2
      years after acute stroke onset. There were no significant differences between the
      levels of blood folate, serum cobalamin and serum creatinine in the acute and
      convalescent phase of all 49 stroke patients. However, we noted a significant
      decrease of blood folate concentrations in a subgroup of patients (n = 25) who
      had increased plasma homocysteine concentrations. Thus the increase in plasma
      homocysteine concentrations in this group of patients may partly be caused by a
      marginal folate deficiency.

PMID- 9156563
TI  - 17 beta-Estradiol and tamoxifen prevent the over-glycosylation of rat trabecular
      bone collagen induced by ovariectomy.
AB  - We have recently demonstrated that ovariectomy in the rat causes over
      glycosylation of collagen which is restricted to trabecular bone. In order to
      obtain further evidence, we studied whether estrogen or tamoxifen treatment
      prevented over-glycosylation of trabecular bone collagen. Forty one-hundred-day
      old female rats were subjected to ovariectomy (n = 30) or sham-operation (n =
      10). Starting the day of the operation, sham-operated rats were treated with
      vehicle, while ovariectomized rats were divided into three groups and treated
      with vehicle (n = 10), estrogen (n = 10) or tamoxifen (n = 10). Five rats from
      each group were sacrificed at 115 and 145 days of age. Femurs and tibiae were
      separated into cortical and trabecular bone, demineralized, hydrolyzed and
      analyzed by HPLC for hydroxylysine glycoside and hydroxyproline content.
      Hydroxylysine glycoside content was expressed as a molar ratio with
      hydroxyproline. The results can be summarized as follows: 1) cortical bone
      collagen glycosylation did not vary among the different groups; 2) over
      glycosylation of trabecular bone collagen observed in the ovariectomized rats was
      prevented by the administration of either 17 beta-estradiol or tamoxifen. These
      data demonstrated that estrogens affect glycosylation of trabecular bone
      collagen.

PMID- 9156564
TI  - Quality management and influential factors for the detection of single metastatic
      cancer cells by reverse transcriptase polymerase chain reaction.
AB  - The sensitive and specific detection of micrometastasis holds great promise for
      earlier staging of cancer patients. By amplification of tissue-specific gene
      expression, the reverse transcriptase polymerase chain reaction (rtPCR) readily
      detects single tumour cells in different tissues. An increasing number of rtPCR
      assays with possible relevance for routine laboratory diagnostic procedures is
      currently being reported in the literature. Interestingly, when used in the
      clinical setting, assays for the same target mRNA perform very differently,
      despite comparable sensitivities and specificities in-vitro. Using rtPCRs
      specific for carcinoembryonic antigen (CEA), prostate-specific antigen (PSA) and
      cytokeratin 18 (CK 18), we have started to systematically investigate, both
      experimentally and in clinical specimens, a number of factors that contribute to
      the varying and seemingly implausible test results. Here we have concentrated on
      sample collection modalities, assay stability and test reproducibility at the
      sensitivity limit. Our results demonstrate in detail that, at the maximum
      sensitivity required for micrometastasis detection, preanalytical and statistical
      influences increasingly become important for the consistency of the assay
      results. We conclude that the prerequisite for translating the results from
      highly sensitive and specific rtPCR assays into clinically relevant data is the
      thorough definition of assay procedures and the number of tests performed on a
      sample. Addressing questions of standardization and quality control management is
      a central aspect yet to be emphasized in assay development and application of
      routine laboratory rtPCR tests in oncology.

PMID- 9156565
TI  - Coexistence of deficiencies of uroporphyrinogen III synthase and decarboxylase in
      a patient with congenital erythropoietic porphyria and in his family.
AB  - A hitherto undescribed dual deficiency of uroporphyrinogen III synthase and
      uroporphyrinogen decarboxylase was observed in the erythrocytes in a 14 year-old
      patient who had presented with congenital erythropoietic porphyria since early
      childhood. Whereas congenital erythropoietic porphyria was metabolically and
      clinically overt, a hereditary deficiency of uroporphyrinogen decarboxylase was
      confirmed by family study. The uroporphyrinogen III synthase activity of the
      propositus was decreased to 26% of the control while his asymptomatic family
      members had activities between 53-65% of the control. Additionally, the
      uroporphyrinogen decarboxylase activity was 55-66% of the control in the patient
      and his family. Family investigations have shown that the two disorders do not
      consistently segregate together. Although urinary porphyrin excretions of
      relatives were in the physiological range, the proportion of coproporphyrin
      isomer I showed a relative increase, which can serve as a biochemical indicator
      for heterozygous uroporphyrinogen III synthase gene carriers.

PMID- 9156566
TI  - Discrimination between normal wildtype and carriers of coagulation factor V
      Leiden mutation by the activated protein C resistance test in the presence of
      factor V deficient plasma.
AB  - Blood samples from 104 patients with clinically suspected thrombophilia were
      analyzed for coagulation factor V Leiden mutation (1691, G-->A) by allele
      specific polymerase chain reaction. In 86 individuals (82.7%), the mutation was
      not detectable, whereas 15 patients (14.4%) were heterozygous and three patients
      (2.9%) were homozygous for factor V Leiden mutation. Plasma samples from these
      individuals were also tested for functional resistance of coagulation factor V to
      activated protein C (activated protein C resistance). This test was performed on
      a Schnitger-Gross coagulometer using an activated partial thromboplastin time
      based activated protein C resistance test modified by applying a 1 : 5 dilution
      with factor V-deficiency plasma. All the individuals negative for factor V Leiden
      mutation were also negative in the functional activated protein C resistance
      test. On the other hand, all patients carrying the mutation revealed pathologic
      results in the activated protein C resistance test. The cutoff value for the
      activated protein C resistance index (> or = 1.7 = negative) was determined by
      testing 31 male and female blood donors. One of them was heterozygous for factor
      V Leiden mutation and had an activated protein C resistance index of 1.4, whereas
      those without factor V Leiden mutation had an activated protein C resistance
      index of 1.9 +/- 0.1 (mean +/- SD). Patients with clinically suspected
      thrombophilia without factor V Leiden mutation had an activated protein C
      resistance index of 2.1 +/- 0.2 (mean +/- SD), whereas patients heterozygous for
      the mutation had an index of 1.5 +/- 0.1 (mean +/- SD). Within the group of
      patients carrying the mutation, the activated protein C resistance test even
      distinguished between heterozygous and three homozygous (activated protein C
      resistance 1.0 to 1.2) carriers. The data demonstrate that the activated protein
      C resistance test in the presence of factor V-deficiency plasma provides a clear
      cut discrimination between normal wildtype and carriers of factor V Leiden
      mutation with a sensitivity and specificity of 100%. Verification of positive
      activated protein C resistance tests can be performed easily with a simple and
      reliable polymerase chain reaction protocol for the 1691, G-->A mutation.

PMID- 9156567
TI  - Comparison of sialic acids excretion in spot urines and 24-hour-urines of
      children and adults.
AB  - Sialic acids comprise all N- and O-acyl derivatives of neuraminic acid and are
      components of glycoproteins and glycolipids. Their concentrations vary
      physiologically with age but also in diseases such as inflammation, neoplastic
      tumours or in inborn genetic disorders causing abnormal sialic acid metabolism.
      Determination of free and bound sialic acids in urine using the thiobarbituric
      acid method according to Warren (J Biol Chem 1959; 234:1971-5) was shown to be
      useful for the diagnosis of diseases that involve sialic acid metabolic
      disorders. This test-also used for the diagnosis of inborn errors of metabolic
      diseases, such as sialidosis, infantile sialic acid storage disease, Salla's
      disease, neuraminidase deficiency and others-should be included in the selective
      screening for storage diseases. With the reported number of mild, juvenile and
      adult forms of genetic disorders increasing, this diagnosis will also be useful
      for teenagers and adults. We therefore considered it important not to confine our
      investigation to children and compared the diagnostic value of 24-hour and spot
      urines. As shown in 24-hour urines (n = 242, 128 males, 114 females) the average
      excretion of sialic acids increases constantly during life, from 67.6 mumol to
      444.0 mumol per day, as does the free (27.5 mumol to 217.1 mumol) and bound
      fraction (40.1 mumol to 226.9 mumol). The relative proportion of free and bound
      sialic acid shows only slight lifetime variations, the free fraction increases
      from about 40 percent the first few years to about 53 percent of total in the
      fifth decade. In the spot urines, the mean ratio of total free sialic acids and
      urinary creatinine (mmol/mol) decreases constantly during the first few decades,
      with a sharp drop during the first years of life (from 3 months-2 years: from
      203.9 to 94.2 and 82.1 to 42.3 respectively; with 10 years: 52.3 and 22.4
      respectively; in the sixth decade: 44.8 and 21.9). Similar findings could also be
      observed in the investigated 24-hour urines (correlation coefficient of ratios, R
      = +0.981). The comparison of 24-hour urines and spot urines confirms the
      reliability of results for spot urines, however, the urine collection over an
      extended period yields additional information.

PMID- 9156568
TI  - The iron content of serum ferritin: physiological importance and diagnostic
      value.
AB  - In this paper we present a method for determining the iron saturation of ferritin
      as a possible independent predictor of iron stores. Serum ferritin was purified
      by immunochemical precipitation, and could be completely recovered from serum
      without any contamination from transferrin. The iron content of the precipitated
      ferritin was determined by flameless atomic absorption spectrophotometry (FAAS)
      and the ferritin-iron saturation was calculated using the original serum ferritin
      concentration. The intra- and inter-assay variation coefficients were 4.2% and
      13.4% respectively. The first results with this assay indicate that serum
      ferritin contains a considerable amount of iron. Furthermore the results show
      that the iron saturation of ferritin in patients with acute phase response is
      significantly lower than the saturation found in healthy volunteers (19.3% and
      24.3% respectively). These results suggest a possible role for the ferritin-iron
      saturation in the assessment of iron stores in patients suffering from acute
      phase response. In addition, the considerable amount of iron in ferritin suggests
      the need to revise the physiological role of this substance in relation to the
      serum iron homeostasis.

PMID- 9156569
TI  - Determination of vanillylmandelic, 5-hydroxyindoleacetic and homovanillic acid in
      urine by isocratic liquid chromatography.
AB  - A new isocratic HPLC method, employing electrochemical detection, is described
      for the determination of urinary vanillylmandelic acid, 5-hydroxyindoleacetic
      acid and homovanillic acid. The main advantages of this technique are:
      simplicity, simultaneous determination of all analytes, the absence of an
      extraction procedure, isocratic elution and low cost. The diluted urine is
      injected onto a C18 reversed phase column. The mobile phase is potassium
      dihydrogenphosphate buffer containing 1-heptanesulphonic acid, methanol and
      acetonitrile. The calibration curves are linear from 0.1 to 50 mg/l; the
      precision data show CV less than 2.36% for within-day assay and less than 2.72%
      for day-to-day assays. The mean recoveries for supplemented samples are 98.2 to
      102.0% for vanillylmandelic acid, 99.6 to 103.9% for 5-hydroxyindoleacetic acid
      and 98.7 to 102.0% for homovanillic acid. In comparisons of the present method
      with Radjaipur's extraction method (Radjaipur M. et al., Eur J Clin Chem Clin
      Biochem 1994; 32:609-13) the slopes for the three analytes were nearly 1, and the
      confidence region of the intercepts was close to 0. In conclusion the technique
      seems to be suitable for routine determination of the three analytes, especially
      for mass screening purposes.

PMID- 9156571
TI  - Proceedings of a symposium on membrane dynamics and permeability. London, United
      Kingdom, 8 September 1995.

PMID- 9156570
TI  - Comparison of the clinical performance of the immunoenzymometric assays for N
      terminal and C-terminal type I collagen telopeptides and the HPLC assay for
      pyridinium cross-links.
AB  - We evaluated the clinical performances of the immunoenzymometric assays for type
      I collagen N-terminal and C-terminal telopeptides and the HPLC assay for total
      deoxypyridinoline, in distinguishing between subjects with a moderately increased
      bone resorption rate (women in postmenopause) and subjects with normal bone
      resorption rate (women in premenopause). The postmenopausal group consisted of 61
      women who had been in menopause for no more than 10 years, while the
      premenopausal group consisted of 52 healthy women with normal menstrual cycles.
      The biochemical markers were measured in a 24 hour urine sample and the results
      expressed as the molar ratio with urinary creatinine. The clinical performances
      were estimated by calculating the accuracy (as the area under a Receiver Operated
      Characteristic (ROC) curve: mean +/- SEM) and the discriminating power (as score)
      of each assay in distinguishing postmenopausal subjects from premenopausal
      subjects. Type I collagen C-terminal telopeptide, type I collagen N-terminal
      telopeptide and total deoxypyridinoline were significantly higher in the
      postmenopausal than in the premenopausal group (p < 0.01). Accuracies of these
      three markers ranged from 66.8 +/- 5.1% to 76.8 +/- 4.3%, while Z scores ranged
      from 3.54 to 5.67. Type I collagen C-terminal telopeptide, type I collagen N
      terminal telopeptide and total deoxypyridinoline were not significantly different
      in their accuracy or discriminating power. All markers were highly correlated
      with coefficients of correlation ranging from 0.61 to 0.77. In summary, this
      study shows that 1) the immunoenzymometric assays for type I collagen N-terminal
      telopeptide and type I collagen C-terminal telopeptide show a high accuracy and
      discriminating power in distinguishing subjects with different bone resorption
      rate; 2) the results obtained with these immunoenzymometric assays are comparable
      to those obtained with the HPLC assay for total deoxypyridinoline. In conclusion
      our data support the use of the immunoenzymometric assays for type I collagen N
      terminal telopeptide and type I collagen C-terminal telopeptide for estimating
      bone resorption.

PMID- 9156572
TI  - Endosomes, receptor tyrosine kinase internalization and signal transduction.
AB  - Upon the binding of insulin or epidermal growth factor to their cognate receptors
      on the liver parenchymal plasmalemma, signal transduction and receptor
      internalization are near co-incident. Indeed, the rapidity and extent of ligand
      mediated receptor internalization into endosomes in liver as well as other organs
      predicts that signal transduction is regulated at this intracellular locus.
      Although internalization has been thought as a mechanism to attenuate ligand
      mediated signal transduction responses, detailed studies of internalized
      receptors in isolated liver endosomes suggest an alternative scenario whereby
      selective signal transduction pathways can be accessed at this locus.

PMID- 9156573
TI  - Trafficking of glucose transporters--signals and mechanisms.
AB  - The uptake of glucose into mammalian cells, catalysed by members of the GLUT
      family of glucose transporters, is regulated by a variety of hormones, growth
      factors and other agents. In adipocytes, skeletal muscle and heart the principal
      regulator is the hormone insulin, which rapidly stimulates glucose uptake by
      bringing about the translocation of the GLUT4 glucose transporter isoform from an
      intracellular vesicular compartment to the cell surface. Recent studies have
      implicated the C-terminal hydrophilic region of this protein as being primarily
      responsible for its insulin-regulated trafficking. In an attempt to identify the
      protein machinery involved in this trafficking, we have used glutathione S
      transferase fusion proteins bearing hydrophilic domains of various GLUT
      transporters in affinity purification experiments on detergent-solubilized
      extracts of 3T3-L1 adipocyte intracellular membranes. The C-terminal region of
      GLUT4 was found specifically to bind a number of polypeptides in these extracts,
      which are therefore candidates for components of the trafficking machinery.
      Although these proteins did not bind to the corresponding region of the more
      widely-distributed GLUT1 glucose transporter isoform, regulation of this
      transporter also appears to be of physiological importance in some cell types. To
      study such regulation we have used as a model system the interleukin-3 (IL-3)
      dependent haemopoietic cell line IC.DP. These cells express a temperature
      sensitive mutane of the v-abl tyrosine kinase, whose activation at the permissive
      temperature permits cell survival in the absence of IL-3 by suppression of
      apoptosis, although the growth factor is still required for proliferation. Both
      IL-3 and activation of the kinase were found to stimulate glucose transport by
      promoting the translocation of GLUT1 to the cell surface. Moreover, inhibition of
      glucose uptake by addition of transport inhibitors markedly increased the rate of
      apoptosis, an effect which could be reversed by the provision of alternative
      energy sources. These observations suggest that the trafficking of GLUT1,
      regulated by growth factors or oncogenes, may play an important role in the
      suppression of apoptosis in haemopoietic cells.

PMID- 9156574
TI  - Control of glucose transport by GLUT1: regulated secretion in an unexpected
      environment.
AB  - Studies designed to elucidate the mechanism of regulation of the GLUT1 isoform of
      the glucose transporter in response to a variety of cellular stresses are
      reviewed. Using ts mutants of vesicular stomatitis virus, it was shown that the
      viral L gene was responsible for the stimulation of glucose transport in infected
      cells. Immunofluorescence of GLUT1 demonstrated that the increase in glucose
      transport was the consequence of a translocation of the transporter from a
      reservoir in cytoplasmic vesicles to the plasma membrane. When cells were cycled
      between deficient and standard medium, the change in glucose transport rates was
      paralleled by a cycling of the transporter between the plasma membrane and the
      cytoplasmic vesicles. The redistribution of GLUT1 was not a consequence of a
      general redistribution of recycling plasma membrane proteins. Instead, the
      findings focus attention on the regulated exocytosis of specific membrane
      constituents in cells that, until recently, were not thought to exhibit this
      capacity.

PMID- 9156575
TI  - Signal transduction and motility of Dictyostelium.
AB  - This review is concerned with the roles of cyclic GMP and Ca(2+) ions in signal
      transduction for chemotaxis of Dictyostelium. These molecules are involved in
      signalling between the cell surface cyclic AMP receptors and cytoskeletal myosin
      II involved in chemotactic cell movement. Evidence is presented for uptake and/or
      efflux of Ca(2+) being regulated by cyclic GMP. The link between Ca(2+), cyclic
      GMP and chemotactic cell movement has been explored using "streamer F" mutants
      whose primary defect is in the structural gene for the cyclic GMP-specific
      phosphodiesterase. This mutation causes the mutants to produce an abnormally
      prolonged peak of cyclic GMP accumulation in response to stimulation with the
      chemoattractant cyclic AMP. The production and relay of cyclic AMP signals is
      normal in these mutants, but certain events associated with movement are (like
      the cyclic GMP response) abnormally prolonged in the mutants. These events
      include Ca(2+) uptake, myosin II association with the cytoskeleton and regulation
      of both myosin heavy and light chain phosphorylation. These changes can be
      correlated with changes in the shape of the amoebae after chemotactic
      stimulation. Other mutants in which the accumulation of cyclic GMP in response to
      cyclic AMP stimulation was absent produced no myosin II responses. A model is
      described in which cyclic GMP (directly or indirectly via Ca(2+) regulates
      accumulation of myosin II on the cytoskeleton by regulating phosphorylation of
      the myosin heavy and light chain kinases.

PMID- 9156576
TI  - Novel leukaemia markers.
AB  - Using synthetic peptide or recombinant protein as immunising antigens we have
      produced monoclonal antibodies and polyclonal antisera directed against targets
      of particular interest in leukaemia diagnosis. In this way we have prepared
      reagents which recognise all T or all B lymphocytes in routinely fixed paraffin
      sections which are unique in this respect. We have also produced monoclonal
      antibodies to molecules potentially involved in specific neoplastic
      transformations, implicated by virtue of the involvement of their genes in
      chromosomal defects in these neoplasms. In particular, we have produced
      antibodies recognising bcl-2, involved in follicular lymphoma, tal-1, involved in
      T-cell acute leukaemias and HRX involved in a variety of hematologic disorders.
      The application of these reagents to diagnosis has so far proved useful. In
      addition their use outside the field of leukaemia diagnosis has proved to be even
      more important in some cases.

PMID- 9156577
TI  - Cellular responses to enteropathogenic Escherichia coli infection.
AB  - Enteropathogenic Escherichia coli (EPEC), first described in the 1940's and
      1950's, remain an important cause of severe infantile diarrhoea in many parts of
      the developing world. EPEC do not produce enterotoxins and are not invasive;
      instead their virulence depends upon exploitation of host cell signalling
      pathways and the host cell cytoskeleton both as a means of colonizing mucosal
      surfaces of the small intestine and causing diarrhoea. Following initial mucosal
      attachment, EPEC secrete 'signalling' proteins and express a surface adhesin,
      intimin, to produce 'attaching & effacing' lesions in the enterocyte brush border
      membrane characterised by localised destruction of brush border microvilli,
      intimate bacterial adhesion and cytoskeletal reorganisation and accretion beneath
      attached bacteria. The pathophysiology of EPEC diarrhoea is also complex and
      probably results from a combination of epithelial cell responses including both
      electrolyte secretion and structural damage.

PMID- 9156578
TI  - Immune receptor repertoire for influenza haemagglutinin.
AB  - An extensive analysis was made of receptor specificity and gene usage in the
      neutralising antibody (mAb) and Class II-restricted T cell responses to influenza
      haemagglutinin (HA) following natural infection of MHC (H-2(k) or H-2(d))
      congenic mice with X31 virus (H3N2 subtype). Despite the diversity of available
      antigenic sites on the HA1 subunit, there was striking immunodominance in the mAb
      response as deduced by sequencing the HA genes of escape mutants and the
      corresponding antibody H and L chain gene rearrangements. Similarly, Class II
      restricted T cell responses of individual donors focused on a single antigenic
      site, or immunodominant peptide; and PCR sequence analysis of T cell receptor
      (alpha beta) gene usage indicated that T cell memory was derived from a single
      progenitor cell. Focusing of the immune repertoire to limited regions of the HA
      molecule during a primary viral infection may be a significant factor in immune
      pressure for antigenic variation.

PMID- 9156579
TI  - Vaccination today and tomorrow.
AB  - The vaccines against infectious diseases in use today are, with few exceptions,
      prepared from the causal agents themselves, either by inactivating them with a
      chemical such as formaldehyde or by attenuating them so that they grow and thus
      evoke an immune response in the natural host but cause no disease. These
      empirical approaches have produced many highly successful vaccines. Increasing
      knowledge at the molecular level of the agents and of the immune response to
      protein antigent is now providing us with the opportunity to design vaccines that
      will elicit protective responses without the need to use the agents themselves.
      The critical issue is to identify the immune responses that correlate with
      protection.

PMID- 9156580
TI  - Watching small molecules move: interrogating ionic channels using neutral
      solutes.
AB  - Whether they are small enough to wriggle through the current-carrying part of an
      ionic channel or big enough to be kept outside and thus able to exert an osmotic
      stress on the channel space, polymers interact with channels in several
      instructive ways. The osmotic stress of excluded polymers allows one to measure
      the number of water molecules that come out of the channel in transitions between
      various "open" to "closed" states. The loss of osmotic activity, due to the
      partial or completely unrestricted admission of small polymers becomes a measure
      of the transfer probabilities of polymers from solution to small cavities; it
      provides an opportunity to study polymer conformation in a perfectly sieved
      preparation. Current fluctuations due to the partial blockage by a transient
      polymer are converted into estimates of times of passage and diffusion constants
      of polymers in channels. These estimates show how a channel whose functional
      states last for milliseconds is able to average over the interactions with
      polymers, interactions that last only microseconds. One sees clearly that in this
      averaging, the macromolecular channel is large enough to react like a macroscopic
      object to the chemical potentials of the species that modulate its activity.

PMID- 9156581
TI  - Novel actions of ryanodine and analogues--perturbers of potassium channels.
AB  - The effects of ryanodine, 9,21-didehydroryanodine and 9,21-didehydroryanodol on
      two types of K(+) channel (a maxi, Ca(2+)-activated, 170pS channel (BK channel)
      and an inward rectifier, stretch sensitive channel of 35 pS conductance (IK
      channel)found in the plasma membrane of locust skeletal muscle have been
      investigated. 10(-9) M-10(-5) M ryanodine irreversibly induced a dose-dependent
      reduction of the reversal potential (V (rev)) of the currents of both channels,
      i.e. from 60 mV in the absence of the alkaloid to 15 mV for 10(-5) M ryanodine,
      measured under physiologically normal K(+) and Na(+) gradients. In both cases the
      change in the ionic selectivity was Ca(2+) -independent. 9,21-didehydroryanodine
      and 9,21-didehyroryanodol also reduced V (rev), but only to 35 mV during
      application of 10(-5) M of these compounds. Additionally, 9,21-didehydroryanodine
      reversibly diminished the conductances of the two K(+) channels. To test the
      hypothesis that ryanoids increase Na permeability by enlarging the K(+) channels,
      the channels were probed with quaternary ammonium ions during ryanoid
      application. When applied to the cytoplasmic face of inside-out patches excised
      from locust muscle membrane, TEA blocked the K(+) channels in a voltage-dependent
      fashion. The dissociation constant (K (d)(0)) for TEA block of the IK channel was
      reduced from 44 mM to 1 mM by 10(-7) M ryanodine, but the voltage-dependence of
      the block was unaffected. Qualitatively similar data were obtained for the BK
      channel. Ryanodine had no effect on the K (d) for cytoplasmically-applied TMA.
      However, the voltage-dependence for TMA block was increased for both K(+)
      channels, from 0.47 to 0.8 with 10(-6) M ryanodine. The effects of ryanodine on
      TEA and TMA block support the hypothesis that ryanodine enlarges the K(+)
      channels so as to facilitate permeation of partially hydrated Na(+) ions.

PMID- 9156582
TI  - Chloride channels and cystic fibrosis of the pancreas.
AB  - Cystic fibrosis (CF) affects approximately 1 in 2000 people making it one of the
      commonest fatal, inherited diseases in the Caucasian population. CF is caused by
      mutations in a cyclic AMP-regulated chloride channel known as CFTR, which is
      found on the apical plasma membrane of many exocrine epithelial cells. In the CF
      pancreas, dysfunction of the CFTR reduces the secretory activity of the tubular
      duct cells, which leads to blockage of the ductal system and eventual fibrosis of
      the whole gland. One possible approach to treating the disease would be to
      activate an alternative chloride channel capable of bypassing defective CFTR. A
      strong candidate for this is a chloride channel regulated by intracellular
      calcium, which has recently been shown to protect the pancreas in transgenic CF
      mice. Pharmacological intervention directed at activating this calcium-activated
      Cl- conductance might provide a possible therapy to treat the problems of
      pancreatic dysfunction in CF.

PMID- 9156583
TI  - Bacterial hemolysins and leukotoxins affect target cells by forming large
      exogenous pores into their plasma membrane: Escherichia coli hemolysin A as a
      case example.
AB  - Many bacteria include among their virulence factors exoproteins which exert
      leukocidal and cytolytic functions and have the ability to form pores in model
      membranes. We show that, at least in the case of the RTX hemolysin produced by
      Escherichia coli (HlyA), formation of pores in planar lipid membranes is
      parallelled by opening of strikingly similar channels in the plasma membrane of
      exposed macrophages. Formation of such lesions in leukocytes can give rise to a
      variety of effects leading altogether to a diminished immune response towards the
      invasive bacteria.

PMID- 9156585
TI  - [The requirements for equipment outfitting and hygiene in interventional
      radiology].

PMID- 9156584
TI  - Membrane pores--from biology to track-etched membranes.
AB  - Flow of ions through narrow pores, either induced in biological membranes or
      created in synthetic membrane filters, exhibits, under appropriate conditions: 1)
      rapid switching of ion current between high and low conducting states; 2)
      selectivity between different ions; 3) inhibition by protons or divalent cations
      with an order of efficacy usually H(+)> Zn(2+)>Ca(2+)>Mg(2+). It seems reasonable
      to conclude that these common properties arise from a common cause-the nature of
      the flow of ions close to a charged surface.

PMID- 9156586
TI  - [CT-supported virtual intra-arterial endoscopy after stent implantation: phantom
      studies and the initial clinical results].
AB  - PURPOSE: To evaluate the facilities of computed tomographic virtual intraarterial
      endoscopy (VIE). Imaging of an intravascular stent in a phantom study and
      clinical assessment in 10 patients. METHODS: The optimal scan parameters for
      different 3 D reconstructions (MIP, SSD, VIE) were determined in a vessel phantom
      with intravascular stent. Furthermore, in vitro stenoses were analysed and
      initial in vivo investigations were performed. RESULTS: The quality of CT
      angiography (CTA) depended on the scanning parameters. VIE allowed the
      reconstruction of the intravascular surface of a stent. CONCLUSION: VIE is a new
      kind of post-processing CTA reconstruction. It permits the visualisation of the
      intravascular structure of a stent. In vitro relevant stenoses were correctly
      detected. First clinical investigations support these results.

PMID- 9156587
TI  - [A comparison of ultrafast computed tomography, magnetic resonance angiography
      and selective angiography for the detection of coronary bypass patency].
AB  - PURPOSE: Validation of ultrafast-CT and MR-angiography (MRA) in comparison with
      angiography for detection of early postsurgical arterial and venous coronary
      artery bypass graft (CABG) patency. METHODS: 21 patients with a total of 55 CABG
      (34 venous and 21 arterial) were studied with angiography, ultrafast-CT (EBT),
      and MRA. RESULTS: With EBT, patency of 43/45 angiographically patent CABG could
      be correctly assessed (sensitivity: 96%). With MRA 26 CABG (17 venous and 9
      arterial) were identified as patent (sensitivity: 67%). It was not possible to
      quantify proximal stenosis of three grafts (> 40%) and to evaluate the distal
      bypass anastomosis with both EBT and MRA. CONCLUSIONS: Ultrafast-CT is a
      promising minimal invasive screening method for the evaluation of venous and
      arterial CABG patency. The diagnostic significance of MRA is remarkably reduced.

PMID- 9156588
TI  - [The helium-3 MRT of pulmonary ventilation: the initial clinical applications].
AB  - PURPOSE: of the study is the visualisation of normal pulmonary ventilation in
      healthy volunteers and the evaluation of abnormalities in patients with different
      lung diseases using 3He magnetic resonance imaging (3He-MRI). MATERIAL AND
      METHODS: Hyperpolarized 3He gas (V = 300 ml, p = 3 x 10(5) Pa, polarised to 35
      45% by optical pumping, provided in special glass cells) was inhaled by eight
      healthy volunteers and ten patients with different lung diseases. A 3D FLASH
      sequence (TR = 11.8 ms; TE = 5 ms; matrix 144 x 256, FOV 350 mm, section
      thickness 7-10 mm, coronal orientation) was performed in a single breath-hold (22
      42 s). Clinical and radiological examinations were available for correlation.
      RESULTS: The studies were successfully carried out in 8/8 volunteers and in 8/10
      patients. The central airways were constantly visualised with intermediate to
      high signal intensity. The lung parenchyma of volunteers with normal ventilatory
      function showed rather homogeneous intermediate to high signal, whereas patients
      with chronic obstructive lung disease and/or pneumonia presented severe signal
      inhomogeneities. Space-occupying lesions and pleural effusion caused large areas
      with little or no signal. The represented the lesion and adjacent ventilatory
      disturbances whose extent had not been presumed from chest x-ray or CT. The
      spatial resolution was higher than in ventilation scintigraphy. CONCLUSION: 3He
      MRI is a promising new modality for the assessment of pulmonary ventilation and
      its anomalies.

PMID- 9156589
TI  - [Magnetic resonance tomography and endosonography in the preoperative staging of
      advanced rectal carcinomas after hyperthermoradiochemotherapy].
AB  - PURPOSE: Comparison of diagnostic accuracy of staging of endorectal sonography
      (ES) and body coil MRI after preoperative hyperthermoradiochemotherapy in
      patients with advanced rectal cancer. METHODS: Prospective analysis of MRI and ES
      in 30 patients after hyperthermoradiochemotherapy and correlation with
      histopathological patterns. RESULTS: T-staging by MRI was correct in 47% and by
      ES in 53% of the cases. Despite similar accuracy of staging in T0- and T1
      tumours, we found different accuracies concerning T2-tumour staging about 63%
      versus 73% (MRI/ES), concerning perirectal infiltration 70% for both techniques,
      concerning invasion of adjacent organs 90% versus 87%, and concerning lymph node
      metastases without respect to the N-stage 63% versus 63%. CONCLUSION: Both
      imaging modalities provide useful information for operation planning despite
      limited accuracy after hyperthermoradiochemotherapy. The body coil MRI does not
      seem to be severely inferior to ES in post-therapeutic staging, despite better
      contour line imaging by ES. With respect to the determination of invasion of
      other organs, MRI seems to be more useful.

PMID- 9156590
TI  - [MR venography of the deep leg veins: signal enhancement by volume infusion].
AB  - PURPOSE: To enhance flow signals in the deep veins of the lower extremity by
      means of a drip infusion. METHODS: Saline solution and diluted contrast media
      were consecutively administered in 8 healthy volunteers by drip infusion (3
      ml/min) via the cubital vein. Imaging of the deep veins in both legs was
      performed using a gradient echo sequence with flow compensation. Changes of the
      intravascular signal-to-noise-ratio (SNR) were correlated with the duration of
      the drip infusion. RESULTS: Improved SNR were detected in each level examined in
      both thigh and calf. SNR increases up to 157% were opposed to decreases of less
      than 16%. The average rise of SNR was up to 55% in the calf veins. CONCLUSION:
      Saline drip infusion is a simple and valuable method for enhancement of venous
      flow signals and should be administered routinely in time-of-flight venographies.

PMID- 9156591
TI  - [Lymph node staging in cervix carcinomas: the results of high-resolution magnetic
      resonance tomography (MRT) with a phased-array body coil].
AB  - PURPOSE: To determine the diagnostic value of high resolution MR imaging with a
      circularly polarised (c.p.) body phased-array coil for the staging of pelvic
      lymph nodes in cervical carcinoma. MATERIAL AND METHODS: 42 patients with
      histologically proven carcinoma of the cervix were studied on a 1.5 T scanner by
      using a c.p. body phased-array coil. The imaging protocol included T2-weighted
      turbo-spin-echo (TSE) and T1-weighted spin-echo sequences pre and post i.v.
      application of Gd-DTPA; slice thickness was 5-7 mm and pixel size 0.53 mm2. Lymph
      nodes with a diameter of > or = 8 mm were considered to have metastatic
      involvement. MR imaging results were compared with histopathologic findings.
      RESULTS: MR imaging showed enlarged lymph nodes (> or = 8 mm) in 16 of 18
      patients with histologic proof of lymph node metastases (sensitivity 89%). In 22
      of 24 cases MR findings were true negative (specificity 92%). Diagnostic accuracy
      was 91%. CONCLUSION: High-resolution MR imaging with a c.p. body phased-array
      coil provides high sensitivity, specificity, and diagnostic accuracy for pelvic
      lymph node staging in cervical carcinoma.

PMID- 9156592
TI  - [A proposal for the MR staging of early rheumatoid arthritis in the
      metacarpophalangeal and proximal interphalangeal joints].
AB  - PURPOSE: MRI can demonstrate pathology of joint disease in the early course of
      rheumatoid arthritis prior to destructions seen on conventional radiographs. In a
      prospective study, we tried to develop a systematical classification of joint
      pathology demonstrated by MRI, which would be essential for scoring the course of
      the disease. PATIENTS AND METHOD: Metacarpophalangeal and interphalangeal joints
      of 48 patients suffering from early rheumatoid arthritis (mean disease duration:
      6.4 months) were evaluated by MRI using a high-resolution transmitter-receiver
      coil. Examinations included 2 mm sliced T2-, T1- and gadolinium enhanced T1-SE
      sequences in coronal and axial orientation. In consideration of pathological
      findings on MRI and histopathogenetical pathways of destruction in rheumatoid
      arthritis a MR-score (0-5) was established. RESULTS: This allowed to score each
      joint examined: score 0 (normal) in 47.8%/49.5%, score 1 in 35.5%/50.5%, score 2
      in 4.2%/0%, score 3 in 10.8%/0%, score 4 in 1.5%/0% of the
      metacarpophalangeal/interphalangeal joints, respectively. CONCLUSIONS: Using the
      MR-score a relative individual destruction number can be calculated, which may be
      used to follow up patients in the early course of rheumatoid arthritis (e.g. drug
      therapy studies). The presented MR scoring system has to be evaluated further in
      longitudinal studies and must be correlated to radiographical and clinical
      findings.

PMID- 9156593
TI  - [Shortening of the measurement time by 1H-MR turbo spectroscopic imaging of the
      brain].
AB  - PURPOSE: Development of a new technique for reduction of measurement time in 1H
      MR spectroscopic imaging of the brain. Optimisation of the sequence parameters in
      volunteer and in patient examinations and comparison to the results obtained with
      conventional 2 D-SI. METHODS: Examination of 20 healthy volunteers and 5 patients
      in a 1.5 T whole-body MR system. In "turbo-spectroscopic imaging" (TSI)
      sequences, a train of spin-echo signals with different phase encoding is acquired
      after each 90 degrees excitation. 32 x 32 matrix elements covered a field of view
      of 20 cm, and additional volume selection was performed by double spin echo
      excitation. Measurement duration 9 min with acquisition of four phase encoding
      steps per TR interval, whereas the corresponding 2 D-SI sequence (TR/TE 2000/272
      ms) took 30 min. RESULTS: The TSI data sets yielded maps of the regional
      distribution of metabolite concentrations with a quality comparable to the 2 D-SI
      results. Signal homogeneity and delineation of brain lesions, however, were
      superior in conventional spectroscopic imaging. The T2 relaxation of the
      metabolites required a reduced sampling interval for each phase-encoded echo, and
      hence the frequency resolution of the corresponding TSI spectra was not always
      sufficient for separating choline and creatine signals. CONCLUSION: With
      measurement durations < 10 min the TSI technique allows in clinical studies a
      combination with single-voxel MRS for accurate quantification and with a
      diagnostic MRI within a total examination time of less than one hour.

PMID- 9156594
TI  - [Radiologically implanted subcutaneous tunneled central venous catheters for
      dialysis: the course and complications].
AB  - PURPOSE: The aim of the present study was to evaluate the efficacy of
      fluoroscopically controlled implantation of subcutaneous tunneled single- or
      double-lumen-catheters for short- and long-term dialysis. PATIENTS AND METHODS:
      In total, 104 patients were implanted with either a single-lumen Demer catheter
      or a Permcath double-lumen catheter into the subclavian vein under fluoroscopic
      control. RESULTS: In 99 of 104 cases (= 95.2%) the implantation remained without
      complications. Implantation-related occurrences included one pneumothorax, one
      mediastinal haematoma and one death. 61.5% of the indwelling catheters remained
      in situ for the intended duration. In 78% of the patients, dialysis was carried
      out to completion. 37 explantations (38.3%) were required due to various factors
      including infection (5), thrombosis (3), dislocation (9) and malfunction (20).
      The average duration of implantation was 59.1 days (range 1-851 days).
      CONCLUSIONS: Fluoroscopic-controlled implantation of subcutaneous tunneled
      catheters for dialysis is superior to surgically implanted catheters with regard
      to lower rates of infections and is equally reliable in respect of rates of
      complication and patency. Thus, this mode of implantation is a safe and reliable
      alternative to other procedures as access for haemodialysis.

PMID- 9156595
TI  - [The value of sonography for the discovery of complications after the
      implantation of silicone gel prostheses for breast augmentation or
      reconstruction].
AB  - PURPOSE: To determine sensitivity and specificity of real-time ultrasonography in
      detecting breast implant complications. MATERIAL AND METHODS: The results of
      preoperative ultrasonography of 121 silicone implants in 65 patients were
      compared with the results after operative implant removal. RESULTS: With a
      sensitivity of 89.25% and a specificity of 92.1%, complications such as gel
      bleeding (n = 43), rupture with leakage (n = 63), and implant dissolution (n = 4)
      become manifest. Capsule formation, fibrosis, siliconoma and calcifications were
      often underestimated in their extent. Negative ultrasonography findings were
      found in 10.7% (n = 13) with positive clinical findings. CONCLUSIONS: The
      combination of clinical and ultrasonography findings leads to the detection of
      implant complications.

PMID- 9156596
TI  - [Carbon dioxide (CO2) as contrast medium for the new installation and follow-up
      of a TIPS].
AB  - PURPOSE: To determine the efficacy of CO2 as negative contrast medium compared
      with iodinated contrast medium in creation and control of TIPS. MATERIAL AND
      METHODS: CO2 was used during TIPS procedures in 33 patients. In 21 patients a
      wedged hepatic venography was obtained for planning the shunt tract. Additional
      TIPS-control DSA was performed in 42 cases by direct portal venography to verify
      the TIPS function and patency. In all cases CO2 gas was used in addition to
      iodinated contrast medium. RESULTS: CO2 produced excellent wedged hepatic
      venographies in all patients. Visualisation of the portal veins and collaterals
      was superior to iodinated contrast medium. The TIPS-control DSA performed with
      CO2 were comparable to those performed with iodinated contrast medium.
      Complications were not observed in our study. CONCLUSION: CO2 is an effective
      contrast medium for TIPS procedures. In particular the visualisation of portal
      veins performed by CO2-wedged hepatic venography is superior to iodinated
      contrast medium.

PMID- 9156597
TI  - [How certain is teleradiological telediagnosis for the tomographic procedure?].
AB  - PURPOSE: To define the value of teleradiographic studies, a comparison was
      carried out between digitised copies of CT examinations of the skull with the
      original images. Differences in image quality obtained from a digital scanner and
      a camera were quantified. MATERIAL AND METHOD: 56 CT examinations of the skull,
      28 of which had discrete abnormalities, were chosen for ROC analysis. The
      original films were digitised with a Vidar VXR-12 scanner and Panasonic WV-160
      and WV-BP 500 cameras. The images were evaluated by five radiologists after image
      transfer with Video Conference software to a personal computer. RESULTS: For the
      analysis of the films the area under the ROC curve was 0.91 +/- 0.04, for the
      digital scanner it was 0.85 +/- 0.04, for camera WV-BP 500 0.89 +/- 0.06 and for
      camera WE-160 0.87 +/- 0.09. Comparison with the film findings showed. a minimal
      p-value of 0.17 which indicated that there was no significant reduction in
      diagnostic value following digitization. CONCLUSION: The probable reason for the
      slight deterioration using the digital scanner was the reduction to 75 dpi
      compared with 134 dpi on the CT films. The cameras produce image noise comparable
      to CT with low window settings and reduced local resolution. We expect similar
      results for CT with soft tissue windows or for MRT of the skull. Conventional
      radiographs containing high local resolution, wide grey scale and low image noise
      would presumably make higher demands on methods of digitization.

PMID- 9156598
TI  - [Bipolar radiofrequency energy in arteries--the experimental results with a new
      catheter system].
AB  - PURPOSE: To evaluate the effects of radiofrequency heated bipolar probes on the
      human arterial wall. METHODS: Under standardised conditions, lesions were set on
      the inner layer of a piece of human cadaver arterial wall, using a radiofrequency
      heated bipolar catheter. These lesions were measured and described both
      macroscopically and microscopically. Lesion size, applied energy levels and
      application conditions were correlated. RESULTS: The size of a lesion depended
      significantly on the size of the catheter, angle and pressure of catheter
      application (p < 0.05) and length of impulse (p = 0.002). There was no influence
      from the energy level employed. It proved impossible to treat calcified plaques.
      The depth of a lesion depended on the angle of catheter application only. No
      perforations were seen. CONCLUSIONS: Radiofrequency-heated bipolar catheters
      ablate the tissue of the arterial wall. Increasing tissue resistance resulting
      from higher energy levels prevents perforation in the experimental set-up.
      Calcified plaques cannot be treated by this method.

PMID- 9156599
TI  - [The adjuvant use of the monoclonal antibody c7E3 Fab in peripheral arterial
      thrombolysis].
AB  - Thrombolysis of arterial occlusions has limitations, e.g. it requires extensive
      time for thrombolysis, occlusions may be resistant to lysis, and the rate of
      reocclusions may be high. c7E3 Fab inhibits platelet aggregation by binding to
      the GPIIb/IIIa receptor on platelets. Experimentally, this monoclonal antibody
      has been shown to decrease, the time required for lysis, and to prevent
      reocclusion. This is the first report on the adjunctive use of c7E3 Fab in
      peripheral arterial occlusions in humans. Three patients with occlusion of the
      iliac or femoropopliteal artery were treated with c7E3 Fab (bolus injection of
      0.25 mg/kg KG + i.v.-application 12 micrograms/min for 12 h). In addition, the
      patients received urokinase (100,000 IU bolus + 100,000 IU/h). Heparin (5,000 IU
      bolus + 1,000 IU/h) and acetylsalicylate (100 mg/day/p.o.). Occlusion length
      ranged between 6-40 cm. Therapy was successful in all patients. During the follow
      up period (4-6 months) no reocclusion occurred. There were no serious side
      effects like major bleeding or thrombocytopenia. We conclude that the applied
      doses appear safe. Even the time required for thrombolysis was short, a
      conclusion in respect of a significant reduction of the time required for lysis
      can be drawn only after further controlled studies.

PMID- 9156600
TI  - [The diagnostic localization of acute gastrointestinal bleeding in a primarily
      negative angiographic finding].

PMID- 9156601
TI  - [Early stent-induced thrombosis in the pelvic circulation: a complication in APC
      resistance].

PMID- 9156602
TI  - [Percutaneous superselective bilateral embolization for the therapy of traumatic
      juvenile arterial priapism].

PMID- 9156603
TI  - [Mucocele of the appendix with pseudomyxoma peritonei--a rare cause of a
      paraneoplastic syndrome].

PMID- 9156604
TI  - [The successful percutaneous revascularization of a subacute renal artery
      obstruction].

PMID- 9156605
TI  - The avian Harderian gland: morphology and immunology.

PMID- 9156606
TI  - The Harderian gland: perspectives.
AB  - This is the three-hundred and second anniversary of the first description of
      Harderian glands by Johann Jakob Harder. Despite more than three centuries of
      study, many features of these glands, including their definition and function,
      are not yet established to everyone's satisfaction. Some topics of Harderian
      biology will be reviewed. Morphology, ontogeny: Mammalian Harderian glands
      secrete largely by exocytosis, which is unusual in a lipid-secreting exocrine
      gland. Polytubular complexes are features of male hamster glands; their
      significance is unknown. Porphyrins: High levels of porphyrin in rodent Harderian
      glands have made this an attractive organ for research on the control of
      porphyrin synthesis. Attempts to use it as a model of human porphyria, however,
      have been disappointing. We do not know the function of Harderian porphyrin. The
      golden (hamster) age: Syrian (golden) hamster Harderian glands show marked sexual
      differences, including porphyrin levels. This has made them a very useful
      experimental animal for endocrine studies. The pineal connection: Rodent
      Harderian glands contain melatonin. Pinealologists often also study Harderian
      glands, and Harderianologists also often study the pineal. This relationship has
      contributed valuable insights to our knowledge of both systems. Lipids: Rodent
      Harderian glands are about 20% lipid by wet weight, and the main secretory
      product is lipid. The main lipid in many animals is 1-alkyl-2, 3-diacylglycerol.
      Harderian gland lipid is extensively studied for insights into lipid
      biochemistry; less has been done on understanding the function of lipids in the
      physiology of the glands. Behavior: Lipids may function as vehicles for pheromone
      secretion. In addition, the possible use of Harderian secretion during cold
      temperatures by gerbils has been noted. Immunology: Bird Harderian glands are
      probably lymphoid organs. This does not seem to be true of mammals, though the
      female Syrian hamster shows large numbers of mast cells. Harderian glands of
      amphibians and reptiles: Research on nonmammalian Harderian glands has been
      limited, though important insights continue to emerge from these studies.

PMID- 9156607
TI  - Comparative histological and ultrastructural studies of the Harderian gland of
      rodents.
AB  - The Harderian glands of six rodents (the Wistar rat, the gerbils Psammomys
      obesus, Gerbillus gerbillus, Meriones crassus, and Meriones lybicus, and the
      gundi, Ctenodactylus vali) were investigated by means of light and transmission
      electron microscopy. In rodents, the Harderian gland consists of branching
      tubules, lined by a single layer of epithelial cells and possessing myoepithelial
      cells within their basal lamina. The Harderian gland contains porphyrins, stored
      as intraluminal masses. The glandular epithelium presents a single cell type (I)
      in Psammomys obesus, two cell types (I, II) in Ctenodactylus vali and the Wistar
      rat, and three cells types (I, II, III) in Gerbillus gerbillus, M. crassus, and
      M. lybicus. The type I and II cells are columnar, characterized by lipid vacuoles
      and well-developed profiles of the smooth endoplasmic reticulum. In Meriones and
      Gerbillus, the type I cell can be distinguished from the type II cell by
      cytoplasmic clefts. In Ctenodactylus vali, the type I cell is characterized by
      cytoplasmic rod-shaped crystalloid structures. These structures are also present
      in the sole cell type of Psammomys obesus. In the Wistar rat, the two cell types
      are distinguished by the number and the size of the lipid vacuoles. The content
      of the vacuole is released primarily by exocytosis, but holocrine and apocrine
      secretion was also noted. The type III cell is pyramidal, characterized by
      numerous mitochondria, and has an extraordinarily well-developed granular
      endoplasmic reticulum organized in concentric lamellae in Gerbillus gerbillus.
      The single excretory duct begins at the hilus. Mast cells, plasma cells,
      macrophages, fenestrated capillaries, and unmyelinated nerve endings with clear
      or dense-cored vesicles are present in the connective tissue. Melanocytes are
      predominant in the gland interstices of Psammomys obesus. The gland is surrounded
      by a thin connective tissue capsule, covered with the endothelium of the orbital
      venous sinus.

PMID- 9156608
TI  - Harderian gland function of Indian tropical palm squirrel, Funambulus pennanti.
AB  - The Harderian gland (HG) of the Indian palm squirrel, F. pennanti, is composed of
      acini of a single type of simple columnar cells with uniform-sized lipid droplets
      and porphyrin (P) in the lumen. Morphologically it presented no sexual dimorphism
      except for the HG weight which revealed that males are acyclic. Circadian study
      of Harderian gland porphyrin (HG-P), plasma melatonin, (aMT) and testosterone
      showed a characteristic two peak cyclicity. In females, HG, HG-P and pineal gland
      weight, and plasma aMT presented an annual inverse relation. Circadian study in
      females only exhibited a two peak cyclicity of HG-P, plasma aMT, and estradiol.
      Pinealectomy (PX) and harderianectomy (HGX) revealed increased HG weight and
      gonad weight in males. Gonadectomy (GX), on the other hand, had no effect on HG
      in males. PX in females brought almost a similar effect as noted for males, but
      HGX had no effect on ovarian weight. GX, interestingly, reduced HG weight and P
      concentration. Daily evening (4:30-5:00) administration of aMT and 5
      methoxytryptamine (5-MT) in males reduced HG weight and HG-P content only in aMT
      treated male and female squirrels, thereby suggesting that HG-P is perhaps
      negatively regulated by pineal gland production and vice versa. Injections of
      gonadotropin and steroids during the sexually inactive phase showed no effect on
      HG-P content in both sexes. Short photoperiod (SP) in both sexes stimulated
      pineal weight without affecting HG weight, while long photoperiod (LP) increased
      HG-P but reduced the plasma aMT level again without affecting HG-P content.
      Continuous dark (CD) decreased HG-P, whereas continuous light was ineffective
      without effecting HG weight in both sexes. In conclusion, HG in this rodent is
      functionally an important gland having diverse physiological effect in both sexes
      sometimes with a very clear HG-pineal-gonad relationship.

PMID- 9156609
TI  - Organogenesis of the Harderian gland: a comparative survey.
AB  - Although research interest in the Harderian gland (HG) has increased during the
      last few years, only a small amount of information exists about its
      organogenesis. In mouse the HG appears in the posterior part of eye region, in
      the form of nonluminated tubules between the sixteenth and eighteenth days of
      gestation. At birth it is still not differentiated histologically. In birds the
      HG originates from the conjunctival epithelium at a late embryonic stage. In the
      English sparrow, Passer domesticus (incubation period of about 13 days), it
      appears between the seventh and the eighth days of incubation. In the chick
      embryo (incubation period of about 21 days) it originates between the eleventh
      and the twelfth days. Among reptiles the lizard Podarcis s. sicula has proved to
      be a useful model to clarify the embryological origin of the orbital glands since
      it possesses the anterior lacrimal gland contiguous to the HG in the medial
      corner of the orbit. The anlage of the orbital glands appears on about the twenty
      second day of development (incubation period of about 43 days) in the form of a
      short tubule projecting from the conjunctival epithelium, at the time of
      development of the nictitating membrane. At this stage the mesenchymal cells
      surrounding the glandular blastema form a well-defined sac, later occupied by the
      orbital glands. From this stage until hatching the growth of the glandular
      blastema continues with the formation of acini which move posteriorly into the
      preformed mesenchymal sac. At the thirty-sixth day of development the more
      lateral acini differentiate into the HG. Only at the forty-first day do the more
      medial acini differentiate into the anterior lacrimal gland. At hatching the HG
      is fully differentiated. In anuran amphibia the primordium of the HG appears
      during the metamorphosis at the time of development of the nictitating membrane.

PMID- 9156610
TI  - [Aspects and perspectives of social medicine. Dedicated to Prof. Dr. Hans
      Schaefer for his 90th birthday].

PMID- 9156611
TI  - [The early history of the German Society of Social Medicine and Prevention].

PMID- 9156612
TI  - [Laudatio for Hans Schaefer on his 90th birthday].

PMID- 9156613
TI  - [Social medicine in teaching and research].

PMID- 9156614
TI  - [Prevention and health promotion: a responsibility of social medicine?].

PMID- 9156615
TI  - [Social medicine and epidemiology: significance for conquering illness].

PMID- 9156616
TI  - [Social medicine and health system research, status and perspectives].

PMID- 9156617
TI  - [Rehabilitation and social medicine].

PMID- 9156618
TI  - [Perspectives in social medicine counseling and expert assessment exemplified by
      the medical service of health insurance].

PMID- 9156619
TI  - [Social medicine and the public health service].

PMID- 9156621
TI  - [Public health and social medicine].

PMID- 9156620
TI  - [Disciplinary organization of medical sociology--a contribution to the dialogue
      with social medicine].
AB  - According to Karl Popper scientific disciplines are characterized by a body of
      observational knowledge, a specific methodology and terminology and a set of more
      or less successful theories. This article tries to delineate the disciplinary
      structure of medical sociology in terms of five important areas of knowledge: 1.
      sociology of health lifestyles (prevention); 2. sociology of patients careers
      (rehabilitation); 3. sociology of client-professional interaction (diagnosis,
      therapy); 4. sociological (social epidemiological) studies of causes of health
      and disease; 5. sociology of health care systems. It is argued that intensified
      exchange according to these areas between the academic disciplines of medical
      sociology and social medicine is needed to generate a significant impact on
      future training and research both in medicine and in public health.

PMID- 9156622
TI  - [Social medicine aspects of addiction medicine].

PMID- 9156623
TI  - [The hospital in transition. Change in functions, structures and hospital
      contents from the social medicine viewpoint].

PMID- 9156624
TI  - [Public health as a cross sectional responsibility. Results of a study of the
      Munich city administration].
AB  - Implementation strategies of Public Health Policy aim at areas of policy even
      beyond the health sector. An empirical study of the administration of the city of
      Munich shows points of reference for intersectoral collaboration. Basic
      structures of the local administration are analysed and results presented showing
      the relevance of health tasks within the responsibility of other local
      departments. Health tasks are spread throughout the city, and other departments
      besides the health department are responsible for health tasks to a varying
      degree. It seems useful to introduce cross-sectional elements into health policy
      strategies.

PMID- 9156625
TI  - [Several aspects of the development of social public health in Mecklenburg before
      1945].
AB  - The rise of social hygiene in Mecklenburg before 1945 is described via examples
      of three scholars of the Rostock University (Julius Uffelmann, Hans Reiter,
      Werner Kollath). By contextualising this rise, the paper attempts to demonstrate
      both the transformation of medical items into disciplines and the change of
      social values of illness and health. This was accompanied by an increasing
      dissemination of medical-biological values and concepts, from which eugenics
      emerged and subsequently served as a general model for constructing a well
      organised and developing society. Thus a growing number of social disciplines
      became subjected to these ideas.

PMID- 9156627
TI  - [Position of psychosocial specialty societies in medicine on recommendations of
      the Presiding MFT Committee on revision of the approbation regulation for
      physicians].

PMID- 9156626
TI  - [A dilemma--public health care].
AB  - The financing of personal health care services has become the crucible to test
      elected governments in the 21st century. Governments are caught between slow
      economic growth, lower personal income for most workers, and the clamour of
      health care for more money. The Western world with an aging population, marginal
      employment and rising unemployment, does not appear to have the capacity to pay
      for all that science and technology can produce and the public wants. Neither
      private nor public financing seem to have developed the machinery to identify
      need, and to balance demand with national economic output. I wish to suggest,
      that although the countries in the industrialised world have travelled different
      routes we have arrived at the same place. The art and science of medicine coupled
      with the human quest for health may simply exceed our productive capacity. The
      organisation and financing of twenty-First Century science and technology is
      nearly dysfunctional, bound by Nineteenth Century values, traditions and custom,
      as we face the next century. This may be the question.

PMID- 9156628
TI  - [A quarter of a century of rehabilitation of psychiatric patients in Germany].
AB  - The past quarter of a century marks the first and decisive phase of mental health
      care reform in Germany and of psychiatric rehabilitation throughout the world.
      During this great awakening, psychiatry passed beyond the custodial system of
      care, where potent therapy instruments were lacking and the connection to
      society, its living standard and progress in medicine had been lost. In Germany,
      the crucial step to modernity was taken with the creation of the Expert
      Commission on Mental Health Care in 1970 to 1975. The birth hour of
      rehabilitation followed the insight produced by Wing and Brown in 1970 and Wing
      and Bennett in 1972 that secondary impairments caused by social deprivation
      during long-term hospital stay can be favourably influenced by means of
      rehabilitation programmes. Inspired by the Expert Commission's report, and
      encouraged further by the recommendations of the Central Institute of Mental
      Health for the State of Baden-Wurttemberg (1987) and of an expert commission for
      the Federal Republic of Germany (1988), the Federal, State and Local governments
      as well as public welfare organizations supplied considerable funds for the
      development of services and programmes aimed at the reintegration of the
      chronically mentally ill and disabled. Job centres, health insurance schemes and
      retirement pension schemes as paying authorities had greater difficulties in
      contributing to the development of a functioning system of rehabilitation
      services for the severely socially disabled mentally ill. Not only the costs were
      involved but also the complexity of the needs for rehabilitation and confusion
      about the definition of the measures and about the distinction from basic needs.
      The needs, objectives and instruments of psychiatric rehabilitation are discussed
      within the context of the present financial situation. In view of the current
      perspectives of decreasing financial and human resources in our society,
      humanitarian and social responsibility for the particularly vulnerable and
      distressed group of the mentally ill and disabled is called for.

PMID- 9156629
TI  - [Prevalence of psychiatric disorders and outcome of social integration of
      homeless men].
AB  - All 52 regular users of a shelter in a medium-sized German city underwent a
      baseline psychiatric examination in 1990. Mental disorders, especially alcohol
      addiction and schizophrenic disorders, were recorded among 40 (77%). After four
      years the residential situation and the number and duration of psychiatric
      hospitalisations was recorded for 42 of these men. 33 of them mentally ill and 9
      with no mental disorders. The four-year follow-up revealed that half the mentally
      ill men were still living in a homeless environment or had died, whereas most
      users with no mental disorder had a home of their own again. Longer-term
      hospitalisation or guardianship was found to have a favourable impact on social
      integration of the homeless mentally ill. Although psychiatric help without the
      consent of those concerned cannot solve the social problem of homelessness, it
      can often improve the living situation of homeless mentally ill patients.

PMID- 9156630
TI  - [Drug utilization by elderly patients in Bremen old age and nursing homes with
      special reference to psychotropic drugs].
AB  - In five homes for the aged in the city of Bremen that were also nursing homes, we
      studied the drug supply and drug intake of 301 inmates with particular reference
      to psychotropics, basing on the available records. The average regular drug
      intake covered 3.99 drugs. Furthermore, prescriptions for an average of 1.16
      additionally required drugs were issued. More than one-quarter of the inmates
      (27.2%) took between 6 to 11 different drugs permanently. More than one half of
      the inmates (50.8%) were given prescriptions for psychotropics; 45.2% took at
      least one psychotropic permanently. Prescription of benzodiazepines of medium or
      long half-time was strikingly frequent; these are in fact drugs that are usually
      unsuitable for administration to elderly persons. As far as
      antidepressants/tranquilisers are concerned, we noticed that tricyclic
      antidepressants were prescribed almost exclusively.

PMID- 9156631
TI  - [Psychology of patient management: evaluation and quality assurance of
      psychosocial management in pediatric oncology].
AB  - Since the introduction of health-care reform in Germany, quality assurance of
      inpatient care is required. In paediatric oncology this also includes quality
      assurance measures of psycho-social care. Care Psychology deals with the
      development, testing and continual improvement of high-quality psycho-social
      care. Based on clinical experience, scientific knowledge and ascertained
      requirements a handbook and manual of service delivery of psycho-social care is
      formulated and tested in everyday practice. Service performance analyses are
      carried out, and verified improvements are re-tested in practice. This, as well
      as additional attempts, should lead to total quality management (TQM) of psycho
      social care in paediatric oncology according to the criteria of the European
      Foundation of Quality Management (EFQM).

PMID- 9156632
TI  - [Quality promotion in public health research].
AB  - One of the common features of the five Public Health Research Centres of Germany
      lies in quality assurance and quality improvement of their research activities.
      The institutionalisation of systems of quality improvement of Public Health
      Research has to be regarded as innovative, hitherto unparalleled, in the German
      context. The article deals with the demands on quality improvement confronting
      empirical research, the possibilities of coming to terms with this challenge, and
      still unresolved problems of implementation. Demands will be outlined in
      discussing quality criteria and processes of empirical research, paying special
      attention to differences between qualitative and quantitative designs of inquiry.
      The concept of quality improvement, developed in the Munich Public Health
      Research Centre, applies two basic strategies to meet these demands: enhancement
      of the transparency of the research process, and the training of research staff.
      Instruments for quality improvement are introduced: some of them may be applied
      by the research team itself (such as study protocol, research diary, team
      discussion) some of them have to be realised by external staff, especially
      responsible for the process of quality improvement, in cooperation with the
      research team (quality circles, training, compilation of written material). In
      conclusion, the implementation of instruments of this kind is discussed,
      concentrating on the problematic cooperation between research team and external
      staff.

PMID- 9156633
TI  - [Autologous early transplantation of nasal mucosa after the most severe eye
      chemical burns].
AB  - The treatment of severe eye burns is still complicated. Since 1984 we have
      performed autologous nasal mucosa transplantation for the severe mucus deficiency
      syndromes often occurring during follow-up. Now we report on our initial
      experience using nasal mucosa transplantation shortly after severe burns.
      PATIENTS: Prospectively, nine patients (eight male, one female) were examined
      after autologous nasal mucosa grafting within 14 days after eye burns. In all
      patients there was an almost complete defect of limbal vascularization, large
      areas of necrotic conjunctiva and prolonged epithelialization problems. The
      patients were followed for an average of 38 months. RESULTS: In all patients the
      subjective complaints lessened and sufficient ocular wetting led to rapid
      reepithelialization. During the follow-up period two patients showed light
      symblephara. In five patients visual acuity improved to > or = 20/200.
      CONCLUSION: Early nasal mucosa transplantation is an additional tool in the
      treatment of severe ocular burns.

PMID- 9156634
TI  - [Biomechanical study of corneal stability after photorefractive keratectomy].
AB  - BACKGROUND: Photorefraktive keratectomy (PRK) is the most frequent refractive
      surgical procedure worldwide. The central corneal thickness is reduced due to
      removal of the anterior stroma, including Bowman's layer, with a laser beam. This
      procedure results in considerable alterations of the corneal structure. What does
      this mean for the mechanical properties of the cornea? METHODS: Intraocular
      pressure was increased via a 180 degrees tilt. Before and during this procedure,
      corneal topography was measured by photokeratoscopy. We examined 26 patients
      after PRK and 25 controls who had not undergone any surgical procedure. RESULTS:
      The corneal center flattened by 0.038 +/- 0.05 dpt (P > 0.05) in the PRK patients
      and by 0.187 +/- 0.045 dpt (P < 0.05) in the control group. PRK patients within 1
      year after operation showed a minimal central corneal steepening, whereas PRK
      patients after more than 1 year showed a reaction similar to that in normal
      corneas (P < 0.05). CONCLUSION: Corneal stability is altered after PRK. After 1
      year corneal stability seems to normalize due to stromal remodelling.

PMID- 9156635
TI  - [Principle and mechanism of action of an ArF excimer laser system with a scanning
      and rotating slit aperture].
AB  - This study was designed to investigate the quality of a scanning and rotating
      slit delivery system of an ArF-Excimer laser (Nidek EC 5000). The ablation
      patterns on PMMA samples were examined by REM. The influence of inhomogeneities
      in the beam profile was simulated on a computer and compared with a conventional
      large-area ablation system. The impairment of the ablation rate by radiation
      absorption of the ablation plume was measured as a function of the repetition
      rate and the application of a fixation ring. The scanning and rotating slit
      delivery system creates extremely smooth ablation patterns. The delivery system
      is very tolerant of small-beam inhomogeneities. The ablation rate is very
      sensitive to the dynamics of the ablation plume. Although the operating procedure
      takes less time with a large-area ablation system, a scanning and rotating
      delivery system has the advantage of reliable and homogeneous removal of corneal
      tissue.

PMID- 9156636
TI  - [Comparative studies with various corneal topography measurement devices].
AB  - PURPOSE: It is difficult to measure the topography of the cornea with high
      resolution and visualize it on a map displaying refraction. This is demonstrated
      by the ongoing improvement and further development of different methods and by
      the fact that users of these techniques are not always satisfied. MATERIALS AND
      METHODS: Five different ring projectors were compared. Spherical and aspherical
      ball standards were used to measure the standard deviation of the refraction of
      the system. A patient group of eight people with healthy eyes was used to compare
      the measurement accuracy and operational errors. Some patients were also measured
      after cataract surgery. The lateral and axial range of the devices was
      determined. RESULTS: The measurement accuracy for ball standards for the five
      devices was below 1/8 D. For the in vivo case in the control group it was below
      1/4 D for four devices. Furthermore, the reproducibility of the results, the
      accuracy of angle determination and the influence of mechanical and optical
      design will be discussed. The study demonstrates applications and limits of this
      measurement method.

PMID- 9156637
TI  - [Reproducibility and validity of a new automatic method of specular microscopy
      analysis of corneal endothelium].
AB  - PURPOSE: This prospective study was designed to test the reproducibility of a new
      automated technique for analyzing the corneal endothelium and to assess the
      validity of the technique by comparing it with a standard method. SUBJECTS AND
      METHODS: We used a contact specular microscope combined with a video camera
      (Tomey EM-1000) and a computer (IBM compatible PC, 486DX33) with suitable
      software (Tomey EM-1100, version 0.94). Video images of the corneal endothelium
      (area: 0.312 mm2) were passed directly into the computer input by means of a
      frame grabber and were automatically processed. The area to be analyzed could be
      varied by location and size (5580-135,150 microns2), depending on the quality of
      the image. Healthy corneas of 67 volunteers (age: 30.9 +/- 8.6 years) were
      examined. One examiner measured cell density three times in each of 42 eyes
      (retest-stability); three different examiners made one measurement in each of 25
      eyes (objectivity). We evaluated the cell density determined by the computer
      after automated analysis and assessed the corrected cell density. This second
      result was obtained after the examiner had corrected the processed image by
      drawing in cell boundaries that the computer had not recognized or erasing cell
      boundaries the computer had sketched in by mistake. Additionally, a photograph of
      the corneal endothelium (specular microscope Bio Optics LSM 2000 A) was obtained
      from 40 volunteers to be used for manual cell counting applying a "fixed-frame"
      technique (validity). RESULTS: The corrected values showed a high retest
      stability (reliability coefficient r = 0.943) and a high objectivity (r = 0.904).
      The values obtained by the automated method (2415 +/- 214 cells/mm2) did not
      differ significantly from those obtained by manual cell counting (2431 +/- 228
      cells/mm2) (P = 0.898). The uncorrected values (2252 +/- 190 cells/mm2) were on
      average 7.2 +/- 2.6% lower than the corrected ones (177 +/- 69 cells/mm2). Retest
      stability (r = 0.856) and objectivity (r = 0.737) of the uncorrected values were
      satisfactory. The uncorrected value was significantly lower than the value of
      manual cell counting (P < 0.001). The size of the analyzed area (range 12,750
      84,708 microns2; average 31,438 +/- 10,655 microns2) had no significant effect on
      cell density (Spearman's correlation coefficient k = -0.150, P = 0.093).
      CONCLUSION: The automated method for analyzing the corneal endothelium quickly
      produces valid, reproducible results in normal corneas, provided that the
      correction mode of the software is applied.

PMID- 9156638
TI  - [Reduction of endothelial cell number by cataract operation with intraocular
      thymoxamine administration. A randomized, double-blind study].
AB  - BACKGROUND: Thymoxamine, an alpha-1-receptor blocker, considerably enhances
      miosis when given intraocularly in combination with acetylcholine. We
      investigated whether intraocular use of thymoxamine 0.02% reduced the number of
      endothelial cells. PATIENTS AND METHODS: After phacoemulsification of 59 eyes,
      either thymoxamine 0.02%, acetylcholine 1.0% or buffered saline solution was
      given intraocularly. With a contact specular microscope, corneal endothelial cell
      photographs were taken on the day before treatment and 3 days and 6 weeks after
      surgery. RESULTS: There were no statistically significant differences between
      endothelial cell counts of eyes treated with thymoxamine (-7.2%), acetylcholine (
      10.2%) or BSS (-9.4%). CONCLUSION: This study shows for the first time that
      thymoxamine, when given in the anterior chamber after phacoemulsification, does
      not cause a greater loss of endothelial cells than acetylcholine or buffered
      saline solution.

PMID- 9156639
TI  - [In vivo imaging of corneal innervation in the human using confocal microscopy].
AB  - To date, descriptions of the structure of corneal innervation have only been
      possible on the basis of histological techniques. Confocal microscopy represents
      a new method for the structural examination of the cornea in vivo. Through our
      examinations we first defined the control group and then proceeded to record the
      reinnervation of donor tissue after perforating keratoplasty. We used the
      confocal slit-scanning video-microscope Microphthal to examine 40 corneas from 20
      normal volunteers, 15 donor corneas and 5 eyes after enucleation for ocular
      tumors. These results were compared to our findings from postoperative checks on
      14 patients after perforating keratoplasty (from 1 month to 2 years). With this
      system we were able to see nerves in the middle and in the superficial stroma.
      The course of these nerves can be followed, as well as their branching in the
      subepithelial plexus. Nerve fibers from superficial stromal nerves penetrate
      Bowman's membrane and create the basal epithelial plexus in the region of the
      basal epithelium. Seven months after perforating keratoplasty the first stromal
      nerves could be seen in the central corneal area. The first central reinnervation
      in the region of Bowman's membrane as well as in the basal epithelium was not
      detected until 15 months after operation. With confocal microscopy we have the
      potential to study the morphology of corneal innervation in vivo and in fresh
      donor tissue. For the first time it is possible to perform non-invasive
      morphological studies of reinnervation of the human cornea after surgical
      treatment.

PMID- 9156640
TI  - [Detection of morphological corneal changes caused by chloroquine therapy using
      confocal in vivo microscopy].
AB  - BACKGROUND: Chloroquine keratopathy is known as a disease with epithelial
      deposits in the cornea. The appearance of corneal changes does not seem to be
      related to dose and duration of treatment. Chloroquine accumulates in lysosomes.
      The purpose of this study was to investigate microscopic changes of corneal
      morphology in patients treated with chloroquine in vivo. PATIENTS AND METHODS:
      Using the confocal slit scanning microscope, we examined 16 patients during
      chloroquine treatment and 4 patients after treatment. The patients' age was
      between 33 and 75 years. They were treated with chloroquine over a minimum period
      of 2 months up to a maximum period of 10 years. RESULTS: In 12 of 20 patients,
      corneal changes were visible. An atypical inverse reflectivity of basal cells in
      comparison to healthy volunteers was found. There were also deposits in the wing
      cell layer. We saw a higher density in the anterior stroma before the appearance
      of epithelial opacities, as well as in cases of keratopathy on slit-lamp
      examination and also after the cessation of chloroquine treatment. In one patient
      with long-term therapy, there were atypically shaped and branched nerves in the
      anterior stroma. CONCLUSIONS: Using confocal microscopy, it was in some cases
      possible to detect changes in the corneal morphology before these changes could
      be detected by slit-lamp examination. As a result of this study we found that
      chloroquine keratopathy is not limited to the epithelium but can affect the
      anterior stroma and possibly neural structures.

PMID- 9156641
TI  - [Inhibition of neovascularization of the eye by dietary factors exemplified by
      isoflavonoids].
AB  - Chronic malignant diseases with neovascularization sometimes seem to improve when
      an exclusively plant-based diet is followed. In order to identify antiangiogenic
      substances in such diets, inhibitory factors such as genistein were isolated. We
      investigated the antiangiogenic substance genistein with regard to the
      possibility of an inhibitory effect on corneal angiogenesis in vivo. METHODS:
      Corneal neovascularization was experimentally induced in NZW rabbits by the use
      of methylcellulose discs loaded with 250 ng basic fibroblast growth factor
      (bFGF). Blood vessels grew from the limbus towards the pellet and were quantified
      under the microscope. Genistein was injected subconjunctivally (0.04 mg
      genistein/day). RESULTS: All eyes which received genistein subconjunctivally
      showed a statistically significant reduction of blood vessels at the limbus (from
      63 +/- 40 vessels to 36 +/- 11 vessels; P = 0.001). Vascularized areas in the
      eyes treated with genistein also decreased, from 21.4 +/- 6.7 mm2 to 10.4 +/- 5.0
      mm2 (P < 0.0001). CONCLUSION: Our results show that components of a plant-based
      diet, such as genistein, inhibit ocular neovascularization in vivo. The genistein
      level rises significantly in human urine following ingestion of soy products, for
      example. Therefore, certain vegetarian diets could have a positive effect on
      ocular diseases characterized by progressive neovascularization.

PMID- 9156642
TI  - [Autoantibody pattern in scleritis and episcleritis].
AB  - BACKGROUND: Episcleritis and scleritis can be caused by various systemic
      disorders, which can be triggered by infectious diseases. We studied the
      autoantibody pattern against various organ-specific and non-organ-specific
      antigens in episcleritis and scleritis patients. MATERIAL AND METHODS: Sera from
      46 patients (episcleritis n = 28, scleritis n = 18) were studied for antibodies
      against nuclei, smooth muscle cells, mitochondria, endothelial cells, sarcolemma,
      liver cells, heart muscle fibrils, parietal cells and thyroid cells by
      immunofluorescence testing. Titers of antibodies against thyroglobulin, laminin,
      keratin and microsomes were evaluated by ELISA. RESULTS: In patients with
      episcleritis the pattern of autoantibodies found was different from that in
      scleritis patients. Thus, in episcleritis the levels of antibodies against
      sarcolemma (32%), parietal cells (25%), laminin (38%), keratin (58%) and
      microsomes (28%) were elevated, while scleritis patients, besides keratin
      antibodies (50%), demonstrated anti-nuclear antibodies (ANA) in 28% of cases.
      These differences were not significant. Approximately 5% of normal control
      patients show these antibodies. CONCLUSIONS: Previous studies have shown that
      episcleritis rarely develops into scleritis. Our results suggest that this may be
      due to different underlying diseases. While 28% of scleritis patients had ANA,
      which may suggest an autoimmune disposition related to collagenosis, episcleritis
      patients had a different autoantibody pattern such as has been found in various
      infectious diseases and diseases for which triggering by infectious organisms
      seems possible, such as anterior uveitis, ankylosing spondylitis and Behcet
      disease. Investigations in larger groups of patients are needed to check the
      statistical significance of these differences.

PMID- 9156643
TI  - [Cellular infiltration of the anterior and posterior eye segment with involvement
      of the peripheral retina, optic atrophy and secondary glaucoma. Non-Hodgkin's
      lymphoma of the central nervous system with ocular involvement at a young age].

PMID- 9156644
TI  - [Hereditary retinal dystrophies].

PMID- 9156645
TI  - [Development of endothelium cell density using fresh and organ cultured tissue. 5
      years after penetrating keratoplasty].
AB  - Many clinical studies have been performed investigating corneal endothelial cell
      loss after penetrating keratoplasty using different preservation methods. Most
      studies, however, included variable follow-up intervals, neglecting the dynamic
      cell loss over the course of time. The aim of this study was to perform
      endothelial cell evaluation 5 years after penetrating keratoplasty using two
      different storage methods. Fifty-four patients were examined 5.2 (+/-0.5) or 4.9
      (+/-0.6) years after surgery. Twenty-four patients had received a cornea stored
      in a moist chamber, 30 patients a cornea preserved by organ culture. All corneas
      had remained clear in the follow-up period. The follow-up periods did not differ
      significantly (P = 0.26). The post-mortem time of moist-chamber-stored tissue was
      significantly lower (P < 0.001), endothelial cell density significantly higher (P
      < 0.001) in organ-culture-preserved corneas. Donor age (P = 0.64) and patient age
      (P = 0.046) did not differ significantly. Average corneal endothelial cell
      density was 1070 (+/-499) cells/mm2 using moist chamber stored and 1095 (+/-497)
      cells/mm2 using organ-culture-preserved tissue (P = 0.82). Five years after
      penetrating keratoplasty, we were not able to find significant differences in
      corneal endothelial cell density using either moist chamber or organ-culture
      preserved corneas. We prefer to use organ culture since there is a lower
      incidence of primary graft failure, tissue with longer postmortem times can be
      used, and surgery can be scheduled.

PMID- 9156646
TI  - [Obtaining donor corneas without eyeball removal].
AB  - The goal of the present study was to compare the quality of 7-mm corneal buttons
      taken directly from donor eyes with commonly obtained transplants. Seven-mm
      porcine corneal specimens and 16-mm cornoscleral specimens were immersed for 3
      and 7 days in Optisol culture medium. After 3 days, ultrasonic pachometry
      revealed a decline to 73% of the original thickness in the 7-mm and to 83% in the
      16-mm specimens. After 8 days, the thickness in both groups had returned to 91%
      of the original values. Light microscopy revealed a homogeneous endothelial layer
      in both groups. Staining with 0.25% Trypan blue revealed only a few dead cells.
      The 7-mm specimens exhibited fewer wrinkles in Descemet's membrane than the 16-mm
      specimens. Scanning electron microscopy of human 7-mm corneal specimens, some
      obtained directly from donor eyes and stored in Optisol and some trephined from
      16-mm corneoscleral specimens after immersion, detected uniformly smooth cutting
      edges in both groups. Even the endothelia displayed no marked differences. Our
      results show that the quality of donor specimens removed at the desired size in
      situ and stored in Optisol equals that of commonly obtained specimens. Further
      investigations must show the feasibility of this procedure in practice.

PMID- 9156647
TI  - [Therapy of advanced amoeba keratitis with keratoplasty a chaud and adjuvant
      cryotherapy].
AB  - BACKGROUND: Since the mid-1980s acanthamoeba keratitis has been diagnosed with
      increasing frequency, especially in contact lens wearers. The assignment to
      specialized centers is often delayed many months and there is hardly any chance
      of controlling the disease by conservative treatment alone. In these cases,
      penetrating keratoplasty offers the only chance for rehabilitation. The
      therapeutic role of penetrating keratoplasty and supportive intraoperative
      cryotherapy is demonstrated by the courses of six patients with unilateral
      acanthamoeba keratitis. PATIENTS AND METHODS: The data of six patients aged 41.2
      (22-63) years with medically uncontrollable acanthamoeba keratitis were evaluated
      retrospectively. The diagnosis was confirmed histologically in all cases. All
      patients were contact lens wearers. They underwent a total of ten keratoplasties
      between November 1986 and January 1995. The donors were 44.8 (23-58) years of
      age. The transplant diameters varied between 7.7 and 9.5 mm. The margins of the
      host cornea were intraoperatively frozen by a cryoprobe in three patients with a
      far advanced stage of corneolimbal parasitic infiltration. RESULTS: During a
      follow-up period of +/-10.2 (1-22) months, five of six eyes were rehabilitated
      with visual acuities between 0.4 and 1.0. One eye went blind after the fourth
      keratoplasty because of uncontrollable secondary glaucoma. After three
      keratoplasties with simultaneous application of cryocoagulation because of an
      especially high risk of persisting acanthamoeba infection, all corneae remained
      clear and free of recurrences. CONCLUSIONS: In advanced acanthamoeba keratitis
      which has not responded to conservative treatment, penetrating keratoplasty not
      only provides elimination of the pathogen, but also good functional results. In
      far advanced stages, the intraoperative application of cryocoagulation for
      parasite elimination in the host cornea seems to be a very effective measure
      against local recurrences of the infection.

PMID- 9156648
TI  - Proceedings of the 5th International Inhalation Symposium. Hannover, Germany, 20
      24 February 1995.

PMID- 9156649
TI  - Effects of CD40 stimulation in the prevention of human EBV-lymphomagenesis.
AB  - CD40 is a molecule present on B lineage cells, both normal and neoplastic.
      Signalling through CD40 has been demonstrated to promote B cell growth and
      differentiation in vitro. In contrast to its effects on normal B cells, we have
      found that CD40 stimulation can inhibit the growth of various aggressive
      histology human B cell lymphomas both in vitro and in vivo. Moreover, using a
      human/mouse chimera model in which human EBV-induced B cell lymphomas can
      spontaneously arise, we have found that CD40 stimulation an prevent the
      occurrence of this human lymphoma in mice. However, normal human B cell
      engraftment and function was not adversely affected in these mice by CD40
      stimulation. This indicates that CD40 stimulation is selective in its effects on
      aggressive histology B cell lymphomas. Thus, CD40 stimulation either by antibody
      or a recombinant soluble ligand, may be of potential clinical use, not only in
      the treatment of EBV-induced B cell lymphomas, but also in their prevention.

PMID- 9156650
TI  - The lysosomotropic amines, chloroquine and hydroxychloroquine: a potentially
      novel therapy for graft-versus-host disease.
AB  - We have recently shown that the lysosomotropic amine, chloroquine, can inhibit
      the development of graft-versus-host disease (GVHD) secondary to minor
      histocompatibility (MiHC) differences in mice. In addition, we have shown that
      both chloroquine and hydroxychloroquine can inhibit T cell responses in vitro to
      minor and major histocompatibility (MHC) antigens. We review the rationale for
      the use of lysosomotropic amines, whose primary mechanism of action appears to be
      inhibition of MHC class II antigen presentation, as therapy for GVHD in humans.
      Used in low concentrations, these agents appear to have no direct effect on T
      cells either in vitro or in vivo although they may have a direct effect at higher
      concentrations. The lysosomotropic amines, at low concentrations, in combination
      with the T cell-specific agent, cyclosporin A, synergistically suppresses the T
      cell response to MiHC and MHC in mouse and in human. We present the initial data
      from the human clinical trials using hydroxychloroquine. We hypothesize that the
      lysosomotropic amines may have unique beneficial effects on immune reconstitution
      following bone marrow transplantation. The lysosomotropic amines,
      hydroxychloroquine and chloroquine, represent agents with unique mechanisms of
      action that may be used to control GVHD in humans.

PMID- 9156651
TI  - DNA methylation and developmental genes in lymphomagenesis--more questions than
      answers?
AB  - There is now considerable evidence suggesting that alterations in the DNA
      methylating machinery play an important role in tumorigenesis and tumour
      progression. For example, focal hypermethylation and generalised genomic
      demethylation are features of many different types of neoplasms. It is thought
      that tumorigenesis and tumour progression may be caused by hypermethylation
      induced mutational events and silencing of genes which control cellular
      proliferation and/or demethylation induced reactivation of genes which may only
      be required during embryological development. Consequently, we have begun to
      investigate the role of DNA methylation and developmental genes in malignant
      lymphoproliferative diseases. Previously, in all cases of non-Hodgkins lymphoma
      and leukemia studied, we have shown that the myogenic developmental gene Myf-3 is
      abnormally hypermethylated. In this review we discuss the possible significance
      of these findings since in vitro studies suggest that Myf-3 may play an important
      role in control of the cell cycle and therefore lymphomagenesis. In vitro and in
      vivo evidence suggests that PAX genes may also have oncogenic potential. The PAX
      family of developmental genes are involved in cellular differentiation,
      proliferation and cell migration. Expression of PAX3 in particular is associated
      with cellular mobility. Our previous studies have indicated that alternate
      regional expression of PAX genes may be controlled by DNA methylation. Therefore,
      we have proposed that abnormal methylation profiles of PAX3 may be associated
      with neoplastic transformation and/or metastatic potential. Results thus far
      reveal that the paired box of PAX3 is abnormally hypermethylated and the homeobox
      abnormally hypomethylated in lymphomas and leukemias. These new findings are
      consistent with our postulate and support the idea that inappropriate methylation
      induced activation or inactivation of developmental genes such as Myf-3 and PAX3
      play an important role in lymphomagenesis and disease progression and that
      inspection of the methylation status of other developmental genes is warranted.

PMID- 9156653
TI  - The retinoblastoma susceptibility gene RB-1 in multiple myeloma.
AB  - Genetic mechanisms leading to the development of multiple myeloma (MM) remain
      poorly understood. Given the frequency of chromosome 13 deletion in MM and the
      localization in 13q14 of the retinoblastoma susceptibility gene RB-1, an
      involvement of RB-1 in MM pathogenesis has been proposed. Moreover, interleukin-6
      (IL-6) has been shown to be the main growth factor for MM in vitro and in vivo.
      The product of the RB-1 gene (pRB) can down-regulate IL-6 gene expression.
      Absence of pRB may then induce an autocrine IL-6 expression in myeloma cells and
      contribute to the autonomous growth of MM. As assessed in this review,
      heterozygous deletion of RB-1 is very common in MM but does not alter gene
      transcription and protein expression. Nevertheless, homozygous deletion of RB-1
      has been identified in some MM patients with advanced disease and in the IL-6
      autocrine human myeloma cell line U266. Thus, even if inactivation of RB-1
      appears to be only a rare and late oncogenic event in MM and is not likely to
      represent the main mechanism involved in IL-6 up-regulation in MM, definitive
      assessment of the actual role played by RB-1 in MM pathogenesis still needs
      further investigation particularly the examination of pRB function.

PMID- 9156652
TI  - Bcl-2 expression in acute myeloblastic leukaemia: relationship with autonomous
      growth and CD34 antigen expression.
AB  - The bcl-2 gene encodes a mitochondrial protein that inhibits the onset of
      apoptosis induced by growth factor withdrawal or cytotoxic agents. Using
      quantitative flow cytometry and expressing bcl-2 levels as the number of
      molecules of equivalent soluble fluorochrome (MESF) per cell, we have shown that
      bcl-2 protein expression in the blast cells from patients with acute myeloblastic
      leukaemia (AML) is heterogeneous, but not related to FAB type. The blast cells
      from AML patients with the capacity to grow and survive autonomously in vitro
      were found to have higher bcl-2 MESF values than those that were dependent upon
      exogenous growth factors. We have previously reported that the blast cells from
      70% of AML patients exhibit autonomous growth and autocrine growth factor
      production in vitro and that this has been shown to be an important indicator of
      poor prognosis in AML. High bcl-2 expression has also been associated with a low
      complete remission rate and poor survival in AML. In the patients whose blast
      cells exhibited autonomous growth, neutralisation of endogenous GM-CSF resulted
      in down-regulation of bcl-2 protein, whereas in blast cells from patients whose
      cells proliferated only in the presence of added growth factors, incorporation of
      recombinant human (rh) GM-CSF in the culture media resulted in up-regulation of
      bcl-2. Because CD34 positivity has been reported as another indicator of poor
      prognosis in AML, we compared bcl-2 expression in cases of CD34 positive AML,
      CD34 negative AML and CD34 positive normal bone marrow cells. Bcl-2 was found to
      be strongly expressed on the CD34+ normal bone marrow cells. The blast cells from
      CD34+ AML patients expressed significantly higher bcl-2 levels than CD34- AML
      patients. In five cases of CD34+ AML, the bcl-2 levels were determined on
      purified CD34+ and CD34- blast cell populations. The CD34+ blast cells were found
      to express significantly higher bcl-2 levels compared with the CD34-blast cells.
      Our data would suggest that quantification of bcl-2 in AML blast cell may be
      useful as a prognostic indicator in AML.

PMID- 9156654
TI  - The mechanisms involved in the impairment of hematopoiesis after autologous bone
      marrow transplantation.
AB  - Hematopoiesis after autologous bone marrow transplantation (BMT) is characterized
      by a prolonged and severe deficiency of marrow progenitors for several years,
      especially of erythroid and megakaryocyte progenitors, while the peripheral blood
      cells and marrow cellularity have reached relatively normal values within a few
      weeks. These anomalies are comparable to those reported for allogeneic BMT,
      despite the absence of any allo-immune reaction or post-graft immunosuppressive
      therapy. Post-graft hematopoietic impairment is the consequence of quantitative
      and qualitative changes involving both stem cell and stromal compartments which
      are expressed by an impaired capacity of stem cell self-renewal and commitment
      towards erythroid and megakaryocytic lineages. Besides the toxicity of
      conditioning regimens, hematopoietic reconstitution using autologous grafts is
      particularly dependent on a combination of factors related to the patient, such
      as underlying disease and pre-graft chemotherapy regimens, and to the graft
      processing itself, such as in vitro purging with chemotherapeutic agents.

PMID- 9156655
TI  - Human herpesvirus type-8 (HHV-8) in haematopoietic neoplasia.
AB  - Human herpesvirus type-8 (HHV-8) is a lymphotropic herpesvirus originally
      identified in Kaposi's sarcoma. Among lymphoproliferative disorders, HHV-8
      infection is restricted to body-cavity-based lymphoma (BCBL) and multicentric
      Castleman's disease (MCD). BCBL are B-cell lymphomas growing in liquid phase in
      the body cavities and most frequently associated with AIDS. BCBL express
      indeterminate phenotypes, in all cases are associated with HHV-8 infection, and
      frequently carry Epstein-Barr virus genomes in the absence of c-MYC
      rearrangements or other genetic lesions characteristic of B-cell lymphomas. The
      clinical outcome of BCBL is poor with a median survival of only few months. MCD
      is an atypical lymphoproliferative disorder which displays marked vascular
      hyperplasia and is commonly associated with Kaposi's sarcoma. HHV-8 infection
      occurs in 100% of AIDS-related MCD and in approximately 40% of AIDS-unrelated
      cases. Overall, the consistency of HHV-8 infection in BCBL and MCD, its
      selectivity throughout the spectrum of lymphoproliferative disorders and the high
      copy number of HHV-8 DNA sequences in infected cells suggest that the virus plays
      a pathogenetic role in these disorders.

PMID- 9156656
TI  - Antisense strategy: biological utility and prospects in the treatment of
      hematological malignancies.
AB  - The use of antisense oligonucleotides for the specific control of cellular genes
      expression has undergone rapid developments recently. Besides the antisense
      approach, which usually targets translation initiation or splicing sites, it is
      also possible to interfere specifically with transcription process through triple
      helix formation (anti-gene strategy) or through the titration of regulatory
      proteins (sense and aptamer approaches). Progresses in oligonucleotides chemistry
      have led to the synthesis of analogs with improved pharmacological properties,
      while their generation from recombinant vectors in situ has improved oligos
      deliver to their nuclear or cytoplasmic targets. Hematological malignancies
      provide an ideal paradigm for the development of antisense therapeutic
      strategies. Many disease-specific molecular lesions have been identified which
      provide suitable targets for systemic in vivo administration of oligonucleotides
      as well as for ex vivo bone marrow purging manipulation. However,
      oligonucleotides have also been shown to bind to unexpected cellular targets and
      to induce various unpredictable biological responses as well. In addition, the
      multi-stage nature of carcinogenesis may indicate that even if successful
      inhibition of a single gene by oligomer is achieved, it may still be insufficient
      to induce a major impact on a malignant clone. Thus, much more basic information
      about both the disease and antisense technology is still required before
      antisense strategy gains the status of an acceptable therapeutical approach.

PMID- 9156657
TI  - Epstein Barr virus in Argentine pediatric Hodgkin's disease.
AB  - Since Hodgkin's disease (HD) is an heterogeneous condition with diverse
      histological and epidemiological subgroups, it seemed worthwhile to investigate
      the Argentine pediatric pattern. Moreover, the presence of Epstein Barr virus
      (EBV) infection occurs at different ages depending on the development status of
      the country. Thus, it was interesting to assess the relation between EBV and HD
      in the Argentine pediatric population. The age distribution profile of our
      pediatric HD patients showed a peak in early childhood which declined towards
      adolescence, closely resembling EBV infection pattern. Male:female ratio of the
      studied population was 3.2:1 and the histological subtype distribution disclosed
      that mixed cellularity HD (MCHD) was the most common, an epidemiological profile
      shared with other developing countries. Fifty percent of assessed HD cases were
      associated with EBV, showing a significantly higher prevalence in the 3-6 years
      old group, indicating a non-random distribution. EBV was also present in most of
      MCHD cases and in some nodular lymphocyte predominance HD (nLPHD) but entirely
      absent in nodular sclerosis HD (NSHD). Both EBV subtypes, namely EBV-1 and EBV-2,
      were detected in studied HD cases. EBV-HD association in the Argentine pediatric
      population reveals typical epidemiological features indicating EBV as the
      aetiologic agent or, alternatively as a cofactor in a considerable percentage of
      such HD cases.

PMID- 9156658
TI  - Serum interleukin-6 levels in adult acute myelogenous leukemia: relationship with
      disease characteristics and outcome.
AB  - Serum interleukin-6 (IL-6) levels were measured in 58 adult patients with newly
      diagnosed acute myelogenous leukemia (AML) using an ELISA method in order to find
      potential clinical correlations. Detectable average levels were 57 +/- 68 pg/ml
      and 52 patients (90%) had higher cytokine levels than normal donors. IL-6 levels
      (115 +/- 102 pg/ml versus 36 +/- 40 pg/ml, p = 0.0001) were higher in patients
      with fever of apparently non infectious origin, and higher levels were associated
      with higher percentage of blasts in the peripheral blood (R = 0.29, p = 0.04) and
      in the bone marrow (R = 0.39, p = 0.003), elevated serum LDH level (R = 0.36, p =
      0.01), hyperbilirubinemia (R = 0.36, p = 0.008), elevated serum GGT level (R =
      0.46, p = 0.003), and elevated serum GOT (R = 0.36, p = 0.008) and GPT levels (R
      = 0.44, p = 0.004). Highest IL-6 levels were observed in FAB M1 (86 +/- 112
      pg/ml), M3 (73 +/- 69 pg/ml), and M6 (92 +/- 60 pg/ml) AML subtypes. Serum IL-6
      levels in AML might be related to both non specific inflammatory reactions and
      the specific biology of the disease.

PMID- 9156660
TI  - N-ras gene point mutations in Brazilian acute myelogenous leukemia patients
      correlate with a poor prognosis.
AB  - The frequency of ras gene mutations varies from 11 to 27% in AML populations from
      the United States and Europe but it seems that there is no study regarding the
      frequency of mutated N-ras gene in patients with AML in South America. In order
      to study the frequency of N-ras gene mutations (exons 1 and 2) in Brazilian
      patients with AML and to evaluate the possible correlation between the presence
      of the mutation and clinical features, 40 patients were analyzed. N-ras mutations
      were identified in DNA samples from eight of 40 AML patients (20%). No
      significant correlation was found between N-ras mutation and age, sex, race,
      response to therapy, FAB subtype or occupational exposure. However, the overall
      survival and AML-free survival were significantly shorter in patients with N-ras
      mutations than in those without these abnormalities.

PMID- 9156659
TI  - Long-term safety of GM-CSF (molgramostim) administration after allogeneic bone
      marrow transplantation for hematologic malignancies: five-year follow-up of a
      double-blind randomized placebo-controlled study.
AB  - In a double-blind, randomized study performed between 1988 and 1990, 40 patients
      undergoing allogeneic BMT from HLA-identical siblings for hematologic
      malignancies received 8 mg/kg/d rHuGM-CSF (molgramostim, n = 20) for 14 days. The
      median neutrophil count on day 14 was significantly higher in the GM-CSF group
      (1.90 vs 0.46 yen 10(9)/L, P < .0001). The incidence of acute GVHD and transplant
      related mortality were comparable. Only two deaths occurred after 6 months; one
      due to pulmonary fibrosis in the GM-CSF group on day 1591, and one due to relapse
      on day 1590 in the placebo group. The Karnofsky score of the 10 survivors, 3 in
      the placebo group and 7 in the GM-CSF group, is 90-100% (median 100%), and none
      has chronic GVHD requiring therapy. There was no evidence of increased relapse in
      the GM-CSF group with only two relapses occurring; both in the placebo group.
      With a follow-up of 4.5-6.8 years (median 5.5 years), these patients are amongst
      the longest surviving patients to have received a recombinant growth factor post
      allograft. We conclude that the administration of GM-CSF after allogeneic BMT
      does not appear to be associated with an increased incidence of chronic GVHD or
      relapse, or of other adverse effects such as the development of myelodysplasia.

PMID- 9156661
TI  - Molecular analysis of minimally differentiated acute myeloid leukemia with
      chromosome 16 inversion.
AB  - We report a 3-year-old girl with minimally differentiated acute myeloid leukemia
      and chromosome 16 inversion (inv 16). Inv 16 is generally associated with acute
      myelomonocytic leukemia with dysplastic eosinophils in the bone marrow (AML
      M4Eo). Recently, molecular analysis showed that a fusion gene is generated by
      this inversion between the CBFB gene on the q arm and the MYH11 gene on the p
      arm. Using reverse transcriptase-polymerase chain reaction analysis, we tried to
      detect CBFB/MYH11 chimeric mRNA in blasts from our patients, however, were unable
      to detect any chimeric mRNA in the blasts: The absence of CBFB/MYH11 transcripts
      in this case suggests that rare chimeric products might be formed as a result of
      inv 16 that could not be detected by the primer sets used in this study. Another
      possibility is that different genes are rearranged on the chromosome 16 with the
      inv 16. More detailed molecular analysis of this case might be necessary in order
      to elucidate these possibility. Analyzing leukemias with inv 16 which do not have
      a typical CBFB/MYH11 chimeric mRNA might lead to understanding an alternative
      pathogenesis for acute leukemia with inv 16.

PMID- 9156662
TI  - Serum levels of TNF, IL-6 and sCD23 correlate with changes in lymphocyte count in
      patients with B-cell chronic lymphocytic leukaemia receiving interferon-alpha
      therapy.
AB  - The control of cell growth and differentiation in B-cell malignancies may be
      regulated by the autocrine production of cytokines, several of which have been
      implicated in the growth and survival of B-cells. The effect of interferon-alpha
      (IFN) therapy in these disorders may be to disrupt autocrine growth or survival
      loops. We have measured levels of circulating IL-1b, IL-6, TNF-a and soluble CD23
      (sCD23) in 8 patients with Binet stage A B-cell chronic lymphocytic leukaemia (B
      CLL) receiving IFN therapy, and compared these with changes in the lymphocyte
      count following IFN therapy. Two patients developed anti-interferon antibodies
      while on IFN therapy, and in both them, the changes in lymphocyte count
      correlated significantly with the titre of anti-interferon antibodies, as well as
      serum levels of IL-6, TNF-a and sCD23. In one patient there was significant
      correlation with levels of IL-1b. One patient, who stopped and restarted IFN
      therapy, demonstrated correlation between lymphocyte count and levels of IL-6 and
      sCD23. In a further two patients, there was correlation with levels of sCD23
      alone, while the remaining three patients showed no correlation between
      lymphocyte count and the serum cytokines measured. These results suggest that IFN
      therapy may alter levels of circulating cytokines in some CLL patients and that
      these effects may be associated with disease progression.

PMID- 9156663
TI  - 2-Chlorodeoxyadenosine as initial therapy for advanced low grade lymphomas.
AB  - In order to evaluate efficacy and safety of 2-chlorodeoxyadenosine (2-CdA) as
      primary therapy of low grade non Hodgkin's lymphoma, a phase II trial of 2-CdA
      was initiated in patients with previously untreated advanced low grade lymphoma.
      Fourteen previously untreated patients with stage III and IV low grade lymphoma
      were enrolled. Patients received 2-CdA 0.1 mg/kg/d by continuous infusion for 7
      days every 28 days, for 1-6 cycles of therapy (median 3.5). Results showed one
      complete response and nine partial responses for an overall response rate of 75%.
      Until now there have only been three responding patients who have had progressive
      disease, with a median follow-up time of 18 months. The major toxicity was bone
      marrow suppression and nine patients stopped therapy prior to a planned six
      cycles because of prolonged cytopenias, primarily thrombocytopenia. Fifteen of 50
      cycles of therapy were associated with neutropenic febrile episodes and there was
      one septic death secondary to Listeriosis. It seems from this small group of
      patients that 2-CdA is an active agent in previously untreated low grade
      lymphoma. Myelosuppression is cumulative and limits the number of cycles of
      therapy which can be given. Future exploration of different doses or schedules of
      this active agent is warranted.

PMID- 9156664
TI  - Salvage treatment after failure or relapse following initial chemotherapy for
      follicular non-Hodgkin's lymphoma.
AB  - In an attempt to further define prognostic factors in patients with follicular
      non-Hodgkin's lymphoma, two subgroups of patients receiving 2nd line therapy; (a)
      those who had failed to achieve CR with initial therapy and (b) those who had
      relapsed after achieving initial CR, were examined. Patients who failed to
      achieve initial remission were not totally refractory to retreatment. Seven of 34
      (21%) who had failed to respond to initial treatment achieved CR following
      treatment with various 'salvage chemotherapy' approaches. There were, however, no
      significant pretreatment prognostic factors that were predictive for response.
      Among patients who relapsed after initial CR, 22 of 54 (41%) achieved a second CR
      following retreatment with conventional chemotherapy approaches. The only factors
      which were significant in predicting for second CR were sex (female) and age (<
      60 years). In both subgroups, patients who achieved CR following 'salvage'
      therapy survived significantly longer than those who responded less favourably.
      These findings emphasise the fact that response to treatment is the major
      predictor of survival among patients with indolent non-Hodgkin's lymphomas.

PMID- 9156665
TI  - Granulocytic sarcomas: clinical, diagnostic and therapeutical aspects.
AB  - Granulocytic sarcomas (GS) are extramedullary tumor masses of immature myeloid
      cells most frequently associated with acute myeloblastic leukemia. We report our
      diagnostic, clinic and therapeutic approaches in the treatment of 6 patients
      affected by GS who presented with different localizations and symptoms:
      mediastinal mass with chest pain, rectal tumor with bowel occlusion, bladder mass
      with acute kidney failure, quadriceps tumor with pain, vertebral localization
      with pain and bowel mass with pain, respectively. The correct diagnosis of GS by
      bone biopsy, the immunohistological evaluation of the tumor masses, the prompt
      use of active drugs in the first line therapy schedule as for acute myeloblastic
      leukemia are the parameters for the achievement of the long-term remission.

PMID- 9156666
TI  - Consolidation therapy with idarubicin, cisplatin and prednisone (CIP) after P
      VABEC regimen in the treatment of intermediate and high grade non-Hodgkin's
      lymphoma of the elderly.
AB  - Aggressive treatments in elderly patients with NHL are often responsible for
      acute complications and increased mortality. The present study confirms that P
      VABEC is able to induce a high CR rate (71%), with an overall response rate of
      92%. The 4-year actuarial OS was 45%, and the FFS was 38%. Despite these good
      results 57% of CRs relapsed in a relatively short time (median 9.5 months; range
      2-47). Because of this we decided to evaluate the role of a consolidation
      schedule (CIP), including idarubicin and cisplatin. The toxicity of P-VABEC/CIP
      regimen was comparable to that of P-VABEC alone. After a median follow-up of 20
      months (range 8-49), 93% of CR patients treated with P-VABEC-CIP were still in
      complete remission. The 4-year actuarial overall survival was 92%, and the
      failure-free survival in CR patients was 72%. The difference in OS and FFS
      between the two groups was statistically significant. These results suggest that
      a short course of additional therapy is feasible in elderly patients treated with
      P-VABEC and may increase the OS and FFS, without adding toxicity.

PMID- 9156669
TI  - Clinical applications of attachment theory.

PMID- 9156667
TI  - Primary adrenal lymphoma associated with adrenal insufficiency: a distinct
      clinical entity.
AB  - We describe a case of a 42 year old male who presented with Addison's disease
      resulting from primary lymphoma of the adrenals. Our case and a review of the
      literature indicates that this distinct entity has some unique clinical and
      radiologic features. In this entity, the lymphoma tends to be extranodal and have
      a poor prognosis. In addition, the computed tomography (CT) images have the
      unique appearance of enlargement of the adrenal gland with maintenance of the
      adreniform shape. We suggest that primary adrenal lymphoma is a distinct clinical
      entity and should be considered in patients with an elevated serum lactate
      dehydrogenase, characteristic CT findings and Addison's disease.

PMID- 9156668
TI  - Sequential intensive treatment with the F-MACHOP regimen (+/- radiotherapy) and
      autologous stem cell transplantation for primary systemic CD30 (Ki-1)--positive
      anaplastic large cell lymphoma in adults.
AB  - Most of the adult patients with primary systemic CD30 (Ki-1)-positive anaplastic
      large cell lymphoma (ALCL) reported in the literature have been treated with
      combination chemotherapy (CHT), with only an occasional patient being
      autotransplanted, mostly after relapse. Here we report a series of 19 patients
      treated at our Institution with a sequential intensive therapeutic program
      including CHT (the F-MACHOP regimen given for 6 cycles), radiotherapy (RT), and
      autologous stem cell transplantation (ASCT) after conditioning with the BAVC
      regimen. Eleven of 19 (58%) patients achieved a complete remission (CR) after
      CHT; 3 after RT and 4 after ASCT (1 patient is still not evaluable for response
      to ASCT). The actuarial overall survival is 100% at a median of 49 months from
      diagnosis and the actuarial disease free survival is 100% at a median of 41
      months from the time CR was reached. These data suggest that ALCL can be
      successfully managed with a sequential intensive treatment that prevents early
      relapses and projects these patients as long-term survivors.

PMID- 9156670
TI  - [Evaluation of acceptable exposure levels to industrial and environmental
      pollutants: problems raised because of the interpretation of epidemiological
      data].
AB  - In order to assess acceptable exposure levels to industrial and environmental
      pollutants, toxicological data must be collected which derive from two principal
      sources: in vivo and in vitro experimental studies and epidemiologic studies on
      exposed subjects. Whatever the extent of the toxicological results obtained on
      animals, epidemiologic data, when available, must take precedence over animal
      toxicity studies for setting up acceptable exposure levels. for several practical
      reasons (identification of exposed groups, adequate exposure gradient), the
      epidemiologic studies aiming at assessing the no-adverse effect levels of
      nongenotoxic chemicals are usually performed on occupationally exposed subjects
      and are cross-sectional. Even when the design of these studies probably exclude
      the interference of methodological biases, the interpretation of their results
      may still raise numerous difficulties. This article underlines three particular
      problems: 1) the adequate characterization of past and current exposure and hence
      the identification of the causal agent. 2) the health significance of the
      biomarkers which have been found to be related to exposure and 3) the
      extrapolation of the observations made on workers to the general population.

PMID- 9156671
TI  - [Vascular abnormalities].
AB  - Formerly, if one would decide to get some interest in vascular anomalies, one
      would be abashed by the multiplicity of classifications, the empiricism of
      treatments but mainly by the poverty of fundamental research due to the lack of
      animal models. Today progress in molecular Biology and imaging allow to establish
      a coherent classification of vascular anomalies. Thanks to the development of
      quantum physics, pulsed dye laser is very efficacious in the treatment of
      capillary malformations (port-wine stains). Plastic surgery and reconstructive
      microsurgery allow wide resection of venous and arteriovenous malformations in
      collaboration with interventional radiology. Finally, recent discoveries in
      molecular genetic will allow the creation of transgenic mice with vascular
      anomalies phenotypically similar to human malformations. So, in the near future,
      we will be able to test experimentally new therapeutic approaches but especially
      set up research protocols directed to a better understanding of the pathogenic
      mechanisms of these vascular anomalies.

PMID- 9156672
TI  - [Hantavirus infection: a "new" exotic zoonosis among us].
AB  - Hantavirus disease is a recently recognized zoonosis. The main vectors are
      infected but healthy wild rodents or laboratory rats. Transmission to man occurs
      via inhalation of aerosolised excretions. Kidneys or lungs are the target organs
      during the disease, but a systemic affection with multi-organ involvement is
      possible, and can be fatal. To date, at least 16 different serotypes of
      hantavirus have been characterized, 8 of them being of clinical importance. Each
      serotype has its own rodent vector and its own geographical spread. In Europe,
      the red bank vole (Clethrionomys glareolus) is the main rodent vector carrying
      the Puumala serotype which is the etiologic agent of a viral affection known as
      nephropathia epidemica (NE). Belgium witnessed in 1993 its most important NE
      outbreak with more than 60 cases in the southern part of the region between
      Sambre and Meuse, Chimay being the main focus.

PMID- 9156673
TI  - Protecting the public: an agenda for all implant societies.

PMID- 9156674
TI  - [The theory and practice of medical support of long-term space missions].
AB  - The present paper gives the basis for a conceptual model of diagnostics in long
      duration, including interplanetary, manned missions, and describes the strategy
      of medical support of the MIR crews. Classification of the microgravity-induced
      syndromes (states) and health problems due to e possible technical failures are
      cited as constituents of the conceptual model of medical support system for
      interplanetary missions. In the light he above, principles of diagnostics during
      interplanetary missions are discussed and applicability of some statistical,
      including multidimensional methods to the diagnostic data analysis is considered.

PMID- 9156675
TI  - [Advancement and goals of the aviation human engineering].
AB  - Analyzed were the efforts of the State Scientific-Research Test Institute of
      Aviation and Space Medicine to weigh and account the human factor in designing
      and upgrading avionics and aviation machinery. Described are the policy of human
      engineering support to the development, evaluation, and operation of aviation
      machinery, and the benefits from the human factor knowledge to the specifications
      for aviation machinery and allowance for the psychophysiological aptitudes of
      human on different phases of development of ergatic aviation systems. Outlined is
      the mainstream of ergonomic enhancement of the quality and safety, and
      humanization of the activities of different aviation specialists.

PMID- 9156676
TI  - [Tolerance of +Gz loads by space physician Poliakov VV during the active phases
      of his 438-days space mission].
AB  - Tolerance of +Gz loads was assessed in space physician V.V. Polyakov during the
      active phases of his record, 438-day space mission. On the phases of insertion
      into orbit the +Gz-tolerance of the space physician was good; a fairly
      satisfactory g-tolerance during departure of orbit was extenuated by wearing of
      two anti-g suits (KARKAS-3 and CENTAUR) and administration of countermeasures
      against the unfavorable effects of space microgravity. His general health state
      and self-rating were not noticeably altered. +Gz loads in the course of descent
      from orbit instigated a syndrome characteristic of return to Earth from prolonged
      microgravity, i.e. a sensation of fierce pressure on the body, difficult
      breathing and speech, sine tachycardia, tachypnea, singular arrhythmias,
      petechial hemorrhage in the back integument, and vestibular/autonomous reactions.
      However, no evidence of any unusual physiological reactions that had never been
      seen in the other cosmonauts donned in the anti-g suits on earlier and less
      extended (from 65- to 366-day) missions were found. Extra systoles were
      registered on the phase of return to Earth after the 438-day but not previous 241
      day mission of the space physician; they were probably associated with aging as
      he made his maiden flight at 47, and the second, at 53. The results speak in
      favor of the countermeasures against the adverse effects of microgravity applied
      during the mission, and the anti-g suits worn on the stage of return to Earth.

PMID- 9156677
TI  - [The informative value of temporal artery sphygmogram for diagnosis visual
      disorders during +Gz-loads].
AB  - In investigation with centrifuge runs at 5 +Gz for 30 s visual disorders of the
      grey sheet type were provoked in three test-subjects by short-time relaxation of
      the leg and abdominal muscles. Alterations in amplitude parameters of the
      temporal artery sphygmogram elicited in 59 centrifuge runs were of the kind
      characterizing the well-marked visual disorders. Application of the linear
      discriminant function including three parameters of sphygmogram allowed to
      identify the visual disorders with a 10.2% error and a confidential probability
      of more than 0.999. Validity of the procedure of identification of dangerous
      states of pilot was attested in real flights with the maneuvering loads up to 5.8
      g. Data of the investigation give the authors the right to recommend the method
      of indirect diagnosis of visual disorders as a tool to tackle the applied
      problems of aviation and space medicine.

PMID- 9156678
TI  - [The problem of hygienic standardization of commercial electric and magnetic
      fields in Russia and other countries].
AB  - Review of standards show that many countries still have no hygienic regulations
      concerning the electric and magnetic fields of commercial frequencies. National
      standards have been developed by only a few countries. In a number of countries
      guidelines for protection from the electric fields have been elaborated with the
      magnetic component disregarded. National standards show a significant difference,
      too. In most cases the maximum admissible levels are approximate and ignore
      potential synergetic biological effects of the agents; many of them do not set an
      adequate coefficient of the hygienic margin or foresee possible carcinogenous
      risk.

PMID- 9156679
TI  - [120-day head-down tilted bedrest study with participation of female subjects:
      tasks and protocols of the studies].
AB  - This paper presents an information on the goals, tasks and protocols of a 120-day
      head-down tilted bedrest study with participation of eight female subjects. It
      describes the use of various methods of research and different countermeasures.

PMID- 9156681
TI  - [Dynamics of the hematological shifts in females during antiorthostatic
      hypokinesia].
AB  - The purpose of the present study was to perform comprehensive hematological
      investigations of females in a 120-day head-down (-5 degrees) bed rest and in the
      period of recovery. Morphometric, cytochemical parameters of erythrocytes and
      lymphocytes, erythropoietic activity and turnover of iron were analyzed in 8
      female subjects assigned into two groups of 4. In group A, countermeasures were
      applied throughout the experiment; in group B, they were used only in the
      recovery period. Shifts observed in a number of parameters of the turnover of
      iron and morphometry of the blood cells are most likely adaptive by nature and
      demonstrate the reaction of blood to the hypokinesia and recovery factors.

PMID- 9156680
TI  - [The wakefulness-sleep cycle during antiorthostatic hypokinesia].
AB  - Studies on the wake-sleep cycle with participation of eight female volunteers
      were performed before, during, and after a 120-day bed rest with the head-end of
      bed tilted down at 6 degrees (HDT). Methods of polysomnography and actography
      were applied. The test-subjects were assigned into 2 groups. Group A was
      prescribed to use countermeasures throughout the experiment; no countermeasures
      was administered by group B. Evidence of significant alteration in sleep
      structure at different time points in HDT is given in comparison with data about
      females of the control group under the conditions of everyday activity. Sleep
      deviations in the subjects were reordered at each of the three points of
      investigation and differed from those in control. HDT was shown to modify the
      sleep structure in experimental groups A and B. A supposition is made that under
      these conditions the dynamics of physical activity during night sleep had an
      adaptive character.

PMID- 9156682
TI  - [The effect of head-down tilt bed rest on metabolism of erythrocytes and
      functional state of membranes in females].
AB  - Metabolism of erythrocytes and the structural/functional state of membranes were
      studied in females in the 120-day head-down bed rest and the subsequent period of
      recovery. As was stated, prolonged bed rest and early recovery cause shifts in
      the metabolic and structural parameters of erythrocytes and ensuing degradation
      of the functional state of erythrocytes, i.e. changes in deformability and
      echinocytosis. The system of countermeasures including exercise and a set of
      alimentary supplements with polysaturated fat acids and antioxidants, proved to
      moderate the changes although it failed to fully eliminate them.

PMID- 9156683
TI  - [Effect of 120-day antiorthostatic hypokinesia on the reproductive function in
      women].
AB  - Original data on the peculiarities of adaptation to and functional status of the
      reproductive system in long-term antiorthostatic hypokinesia (AOH) have been
      obtained. The studies involved eight healthy female volunteers aged 26-37 years
      who were exposed to the head-down tilt (-6 degrees) for 120 days. The test
      subjects were divided into 2 groups of 4 persons each. In Group A, the
      countermeasures, i.e. physical exercise and pharmacological means, were used. In
      Group B, at no time did the test subjects use the countermeasures throughout the
      120-day AOH. With and without the countermeasures, hypokinesia was found to
      impact the female reproductive system developing clinical symptoms of deficiency
      of the menstrual lutein phase and giving rise to small inclusions of functional
      fluids in the ovaries. Within 6 months after AOH, the ovarial function of the
      test subjects was fully recovered which may be indicative of the functional
      character of changes. These changes can be explained by dissociation of the
      functional relations in the hypothalamo-hypophyseal-ovarial system manifested by
      increases in the plasmic concentrations of luteinizing hormone (LH) against
      normal levels of follicle-stimulating hormone (FSH) and prolactin, and moderately
      increased levels of testosterone, relative hyperestrogenemia and
      hypoprogesteronemia. These clinical and hormonal developments are contrary to the
      observations usually made in various models of stress. Similarity of the hormonal
      profiles under hypokinesia and long-term immersion of female swimmers may be
      ascribed to common mechanisms underlying the disturbance of the reproductive
      function.

PMID- 9156684
TI  - [Tolerance of +Gx-loads by females before and after a 120-day hypokinesia].
AB  - The goal of the work was to study female tolerance of g-loads before and after
      simulated weightlessness, and evaluate the effectiveness of countermeasures and
      anti-g means proposed for space flight. Centrifuge with a 7.25 m arm was used for
      29 runs of 8 female subjects. The subjects were exposed to the transverse loads
      (+GX) at 8.2 g on a special regimen with the total run time of 9 min to simulate
      the ballistic descent from orbit in a SOYUZ-TM vehicle. Baseline tolerance of the
      females to transverse loads up to +8GX was good and satisfactory. Following 120
      days of bed rest without the countermeasures or the anti-g suit g-tolerance was
      significantly lowered as evidenced by visual disorders in 67% of cases and
      exaggerated, if compared with the pre-hypokinesia levels, heart and respiration
      rates, i.e. 20% and 23.5%, respectively. The countermeasures and anti-g suit
      Centaur maintained g-tolerance at essentially the baseline level and precluded
      visual disorders. Results of the study speak in favor of the countermeasures and
      anti-g means used by the females in simulated long-duration weightlessness which
      can be recommended for the final phase of extended space mission.

PMID- 9156685
TI  - [Experience in diagnosis and treatment of dental caries and its complications in
      persons on space mission and in long-term hypokinesia].

PMID- 9156686
TI  - In defense of weight phobia as the central organizing motive in anorexia nervosa:
      historical and cultural arguments for a culture-sensitive psychological
      conception.
AB  - OBJECTIVE: Recently several proposals at dropping weight phobia as the central
      criterion for the differential diagnosis of anorexia nervosa have been advanced,
      aiming at establishing a new diagnostic category including any self-induced
      weight loss. The validity of weight phobia as a diagnostic criterion is defended.
      METHODS: After summarizing clinical arguments, four groups of culturally or
      historically remote cases of self-induced weight loss or refusal of food are
      analyzed in regard to the presence of weight phobia and clinical similarity to
      modern anorexia nervosa (extreme fasting in the Third World, in the European late
      Middle Ages, early modern times, and late 19th century). RESULTS: It is
      demonstrated that modern Western anorexia nervosa with weight phobia is clearly
      distinct from other groups of cases of extreme fasting without weight phobia.
      DISCUSSION: It is concluded that the psychological motive of weight phobia should
      remain the central criterion for the differential diagnosis of anorexia nervosa.

PMID- 9156687
TI  - Course and outcome in adolescent anorexia nervosa.
AB  - OBJECTIVE: To investigate course, outcome, and psychiatric comorbidity in
      adolescent anorexia nervosa by repeated follow-up assessment. METHOD: Thirty-four
      subjects (88%) of an original sample of 39 inpatients were followed up personally
      3 and 7 years after discharge and classified according to DSM-III-R eating
      disorder categories. Standardized psychometric instruments were used to assess
      specific eating disorder symptoms, concomitant general psychopathology, and
      comorbid psychiatric diagnoses. RESULTS: After 7 years, 1 patient (3%) had
      anorexia nervosa, 4 patients (12%) bulimia nervosa, and 10 patients (29%) eating
      disorder not otherwise specified (EDNOS). Anxiety disorders (41%) and affective
      disorders (18%) were the most prevalent comorbid psychiatric disorders.
      Concomitant general psychopathology was significantly related to the outcome of
      the eating disorder. CONCLUSIONS: According to our results, the majority of
      former adolescent anorexic inpatients had shown substantial improvement in their
      eating disorders symptomatology after 7 years. Patients with persisting eating
      disorders mostly suffered from restrictive symptoms. The prevalence and
      distribution of psychiatric comorbidity were similar to those of adult-onset
      anorexia nervosa. Subjects with a worse outcome of the eating disorder also
      displayed higher levels of general psychopathology.

PMID- 9156688
TI  - Body weight in acute anorexia nervosa and at follow-up assessed with percentiles
      for the body mass index: implications of a low body weight at referral.
AB  - OBJECTIVE: A systematic epidemiological comparison of body weights of patients
      with anorexia nervosa can be enhanced by the use of age percentiles for the body
      mass index. METHOD: To demonstrate the feasibility of this approach, body mass
      indices of 81 female adolescents with anorexia nervosa were calculated from
      anthropometric data upon admission for inpatient treatment and at follow-up and
      set into relationship to the age-dependent distribution of the body mass index in
      a large and representative sample of the German population. The percentiles were
      used to visualize the weight increase over time of each former patient by
      aligning the body mass index at referral with the respective body mass index at
      follow-up. RESULTS: Upon admission most adolescents had body mass indices below
      the third age centile. The distribution of body mass indices at outcome suggests
      a continuum between death of complications related to starvation, chronic
      anorexia, residual anorexia, and a low body weight Patients with very low body
      weights at referral had a poor prognosis, because their body weights tended to
      remain below the minimal normal weight for height. These conditions were
      statistically best described by categorical analysis, because they were nonlinear
      to a certain extent. DISCUSSION: The results indicate that the body mass index at
      referral influences the amount of weight that an individual patient gains in the
      future.

PMID- 9156689
TI  - Use of percentiles for the body mass index in anorexia nervosa: diagnostic,
      epidemiological, and therapeutic considerations.
AB  - OBJECTIVE: Percentiles for the body mass index (BMI) offer a possibility to
      epidemiologically assess the linear weight criterion of 85% average body weight
      commonly used for the diagnosis of anorexia nervosa. METHOD: BMI values
      corresponding to 85% average body weight were calculated and assessed with
      percentiles derived from epidemiological studies in both the United States and
      Germany. The underweight range was characterized epidemiologically. RESULTS: The
      weight criterion used for the diagnosis of anorexia nervosa corresponds to BMI
      values between the 5th and 10th centiles in both populations. In epidemiological
      terms the lowest BMI values in individuals aged 10 years and older occur during
      adolescence. In the general population BMI values <16 kg/m2 are rarely observed.
      Upon the use of higher BMI cutoffs in the underweight range females clearly
      predominate. The BMI increase associated with the 5th or 10th centile in the age
      range between 18 and 30 years is quite low suggesting that many underweight
      females in the general population gain only minimal weight during this age span.
      DISCUSSION: The diagnostic, epidemiological, and therapeutic implications for
      anorexia nervosa are discussed.

PMID- 9156690
TI  - Clinical correlates of anorexia nervosa subtypes.
AB  - OBJECTIVE: Past research has suggested that subtypes of anorexia nervosa
      (restricting vs. binge eating/purging) correspond to differing degrees of
      impulsivity and personality psychopathology. We further investigated potential
      differences between these diagnostic subtypes. METHOD: We compared restricting
      anorexics (n = 100) to binge/purging anorexics (n = 71) with regard to symptom
      presentation and history, impulsivity, eating and related attitudes (Eating
      Disorders Inventory), and personality psychopathology. RESULTS: We found that the
      two diagnostic subtypes did not differ in age at intake, body mass index at
      intake, or age at first diet. Binge/purging anorexics were more likely than
      restricters to have attempted suicide or engaged in stealing, but the two groups
      did not differ in likelihood of having engaged in self-injury or in reported drug
      problems. The two anorexia nervosa subtypes did not differ in age at onset of
      menses, likelihood of having engaged in masturbation or sexual intercourse, age
      of onset of sexual activity, or satisfaction with current levels of sexual
      activity. Likewise, the two groups of anorexia nervosa patients did not differ
      with regard to scores on the Eating Disorders Inventory or Millon personality
      measures. DISCUSSION: Results are discussed in relation to the results of past
      research as well as historical fluctuation in the diagnosis of anorexia nervosa
      subtypes. We propose that subtyping may be less useful than consideration of
      eating disorder symptoms along continua.

PMID- 9156691
TI  - Corynebacterium urealyticum (CDC Group D2) associated with staghorn calculus:
      treatment by percutaneous debulking and chemolysis.
AB  - We report the formation of a staghorn calculus in a transplanted kidney caused by
      infection with a urea-splitting Corynebacterium group D2 organism. The stone was
      debulked percutaneously followed by intravenous vancomycin administration and
      urinary acidification with oral acetohydroxamic acid, leading to clearance of
      nearly all of the stone.

PMID- 9156692
TI  - Caffeine urinary metabolite ratios as markers of enzyme activity: a theoretical
      assessment.
AB  - At least six urinary metabolite ratios of caffeine have been proposed as probes
      for in vivo CYP1A2 activity and three for in vivo NAT2 activity. Claims for the
      frequency distribution of the activity of CYP1A2 based on these empirical ratios
      have varied from log-normal to trimodal. We have examined the validity of these
      nine ratios by developing computer simulations using values reported in the
      literature for the kinetic parameters of caffeine and its metabolites. The
      results show that the sensitivity of the ratios to confounding variables is, in
      some cases, greater than their sensitivity to the activity of the enzyme that
      they are intended to mark. The six CYP1A2 ratios did not exhibit the same pattern
      of dependency on confounding variables which, in turn, resulted in different
      shapes of population distributions for each ratio as enzyme activity was varied
      systematically. Although the dependency of the three NAT2 ratios on confounding
      variable was less marked, they also showed different patterns of dependency. The
      outcomes of the simulations were consistent with much of the experimental data on
      caffeine metabolite ratios. To support the findings from the simulations,
      simplified equations for each metabolite ratio were derived which emphasize the
      dominant determinants. With some of the CYP1A2 ratios urine flow was significant
      to the point where its variance and heterogeneity between populations could lead
      to spurious detection of polymorphism in CYP1A2 function. Also, if the
      variability of a dominant confounding factor was high and sensitivity of the
      ratio to intrinsic CYP1A2 activity was low, any polymorphism in the latter would
      be obscured. When a specific time interval was defined for urine collection, this
      time was shown to be a critical factor in the ability to discriminate bimodality
      in some of the ratios, when a marked polymorphism in enzyme activity was assumed.
      Those ratios which have shown no evidence for bimodality in CYP1A2 function in
      experimental studies are inherently more discriminant of such heterogeneity
      compared to those ratios which have been claimed to detect polymorphism of CYP1A2
      from experimental data. While recommending a 'best buy' from amongst the caffeine
      urinary metabolite ratios, we favour plasma/saliva indices (caffeine half-life or
      paraxanthine/caffeine ratio in a spot sample).

PMID- 9156693
TI  - Lung cancer risk in relation to the CYP2E1 Rsa I genetic polymorphism among
      African-Americans and Caucasians in Los Angeles County.
AB  - Genetic polymorphisms in the activation or detoxication of carcinogens, such as
      those in tobacco smoke, may produce differences in individual susceptibility to
      lung cancer. The cytochrome P450 CYP2E1 is an enzyme involved in the metabolism
      of nitrosamines in tobacco smoke. A polymorphism of CYP2E1 detectable by the
      restriction enzyme Rsa I may be functionally important because it is located in a
      putative binding site for the transcription factor HNF-1 and has been associated
      with higher levels of CYP2E1 transcription. It is conceivable that this CYP2E1
      Rsa I polymorphism might contribute to differences in susceptibility to lung
      cancer. We conducted a case-control study of patients with incident lung cancer
      and population controls in Los Angeles County to examine the association between
      the CYP2E1 Rsa I polymorphism and lung cancer risk among African-Americans and
      Caucasians. Samples of white blood cell DNA sufficient for determination of the
      CYP2E1 Rsa I genotype by a polymerase chain reaction-based assay were obtained
      from 341 cases and 706 controls with data on lifetime smoking history. No
      subjects were homozygous for the CYP2E1 Rsa I rare c2 allele. The rare c2 allele
      was not associated with an increased risk of lung cancer (adjusted odds ratio, OR
      0.72; 95% confidence interval, CI = 0.35-1.46). Among the population controls the
      percentage of subjects carrying the rare c2 allele was lower (p = 0.002) among
      African-Americans (2%) compared with Caucasians (8%). However, the association
      between the CYP2E1 Rsa I genotype and lung cancer risk did not differ between
      ethnic groups. There was no important association between the CYP2E1 Rsa I
      genotype and lung cancer risk in analyses stratified by cell-type, smoking
      history, gender, occupational asbestos exposure, and dietary intake of
      antioxidants vitamin C, vitamin E or beta carotene. Due to the low frequency of
      the c2 allele in these populations, larger studies would be necessary to rule out
      a modest association between the CYP2E1 Rsa I polymorphism and lung cancer risk.

PMID- 9156695
TI  - Genotyping of the polymorphic N-acetyltransferase (NAT2*) gene locus in two
      native African populations.
AB  - The hepatic N-acetyltransferase enzyme encoded by the NAT2* gene locus is
      responsible for the human polymorphic acetylation of numerous arylamine or
      hydrazine-containing drugs and xenobiotics including AIDS-related therapeutic
      agents such as isoniazid and sulphonamides. The genetic basis underlying the
      human acetylation polymorphism has been extensively studied in several
      populations but native African populations were poorly documented. In the present
      study, 117 unrelated black Africans, namely Dogons from Mali and Gabonese, were
      investigated for NAT2* allelic variability and genotype distribution. Thirteen
      NAT2* alleles were unambiguously identified by combined use of allele-specific
      reamplifications and restriction endonuclease digestions. Our results confirm the
      African origin of G191->A substitution in the NAT2* coding region which was
      previously associated with slow acetylation in African-Americans. The finding of
      high allelic diversity in the studied populations is consistent with the
      hypothesis of a single African origin for NAT2*-associated polymorphism. Finally,
      no excess of the slow acetylator phenotype is predicted in these populations,
      implying no need for fitting NAT2* polymorphism-sensitive therapies to black
      Africans, compared to Caucasians.

PMID- 9156694
TI  - Evaluation of caffeine as a test drug for CYP1A2, NAT2 and CYP2E1 phenotyping in
      man by in vivo versus in vitro correlations.
AB  - Caffeine is used to phenotype subjects in vivo for the cytochrome P450 isoforms
      CYP1A2 and CYP2E1, and for N-acetyltransferase type 2 (NAT2). However, how much
      of the variation in phenotyping parameters may be attributed to variations in
      CYP1A2 and CYP2E1 activities has not been determined. Therefore, this study
      intraindividually compared enzyme activities and/or content in liver samples with
      pharmacokinetic parameters of caffeine in vivo after administration of a test
      dose in 25 patients undergoing hepatectomy. Parameters measured in vitro were the
      high affinity components of caffeine 3-demethylation and phenacetin 0
      deethylation, microsomal CYP1A2 and CYP2E1 immunoreactivity, and cytosolic
      sulfamethazine N-acetylation. Caffeine parameters in vivo included caffeine
      clearance from plasma and/or saliva, paraxanthine/caffeine ratios in plasma and
      saliva, plasma theophylline/caffeine ratio, and several metabolite ratios from
      spot urine sampled 6 h postdose. Correlations between parameters were determined
      using weighted linear regression analyses. Caffeine clearance and
      paraxanthine/caffeine ratios correlated most highly to intrinsic clearance of
      caffeine 3-demethylation and to CYP1A2 immunoreactivity (r= 0.584-0.82), whereas
      urinary CYP1A2 ratios correlated less strongly with CYP1A2 parameters in vitro.
      Assignment of acetylator phenotype by urinary NAT2 ratios was concordant with
      sulfamethazine-N-acetylation in vitro. In contrast to CYP1A2 parameters in vitro,
      CYP2E1 immunoreactivity was not related to the theophylline/caffeine plasma
      ratio. CYP1A2 activity, thus, is the major determinant of caffeine clearance and
      the paraxanthine/caffeine ratios in vivo, of which the saliva ratio 6 h postdose
      appears as the most advantageous parameter. The results confirm that phenotyping
      using caffeine provides valid estimates of CYP1A2 and NAT2 activity.

PMID- 9156697
TI  - Management ... New York City hospitals are catching up in the efficiency
      department.

PMID- 9156696
TI  - Simultaneous characterization of glutathione S-transferase M1 and T1
      polymorphisms by polymerase chain reaction in American whites and blacks.
AB  - Human glutathione S-transferase (GST) M1 and T1 enzymes exhibit genetic
      polymorphism, with a percentage of normal individuals exhibiting a homozygous
      deletion of the relevant genes. We established a differential polymerase chain
      reaction (PCR) technique to simultaneously characterize inactivating mutations
      responsible for the null alleles of GSTM1 and GSTT1. Primers for GSTM1,GSTT1,and
      for beta-globin (as a positive control) were used to simultaneously amplify all
      three gene products from leukocyte DNA from 416 normal healthy human volunteers.
      Identical GSTM1 and CSTT1 genotypes were obtained using nine samples processed
      either separately or simultaneously for GSTM1 and GSTT1. The frequency of the
      null genotype for GSTM1 was higher in whites (114/213 or 53.5% vs 56/203 or
      27.6%, p < 0.001) and for GSTT1 was higher in blacks (49/203 or 24.1% vs 32/213
      or 15.0%, p = 0.019). The observed frequency of the 'double null' genotype for
      both GSTM1 and GSTT1 was not significantly different from that predicted if both
      polymorphisms were independent (p = 0.102) and did not differ by race (p = 0.120)
      or sex (p = 0.800). There was a higher frequency of the GSTM1 null genotype among
      females than males (92/202 or 45.5% vs 78/214 or 36.4%, p = 0.049). These results
      demonstrate that this PCR method is a simple and reliable tool to simultaneously
      characterize both GSTM1 and GSTT1 null genotypes.

PMID- 9156698
TI  - Internet ... very few hospitals are surfing it right now.

PMID- 9156699
TI  - Proceedings of the 8th Tokyo Symposium on Growth Hormone and Related Factors.
      February 17, 1996.

PMID- 9156700
TI  - [Sexuality and religions].

PMID- 9156701
TI  - [Axillary node removal prepared by liposuction and assisted by endoscopy in the
      surgical treatment of breast cancers].

PMID- 9156702
TI  - [Future organization of oncologic gynecology: results of an international
      survey].

PMID- 9156703
TI  - [AIDS and pregnancy].

PMID- 9156704
TI  - [Is endometriosis an immunological disease?].

PMID- 9156705
TI  - [Could male infertility become hereditary?].

PMID- 9156706
TI  - [Is infertility hereditary?].

PMID- 9156707
TI  - [Local vaginal therapies].

PMID- 9156708
TI  - [Prognostic role of age and base hormonal levels in infertility treatment].

PMID- 9156709
TI  - [Chance child, desired child, wanted child].

PMID- 9156710
TI  - [Treatment of ovarian cysts by laparoscopy].
AB  - OBJECTIVE: to define limits, risks and results in the long term of laparoscopic
      treatment of ovarian tumors. METHOD: retrospective study of adnexal tumors
      managed initially by laparoscopy from January 1986 to December 1992, among which
      9 cancers, 25 borderline tumors, and 769 benign lesions. The ultrasonographic
      appearance was known for 698 of 803 lesions. 86 patients were postmenopausal (92
      lesions). RESULTS: we treated 191 functional cysts, 160 serous cystadenomas, 178
      endometriomas, 105 dermoid cysts, 39 mucinous cystadenomas and 96 miscellaneous
      lesions among which fibrothecomas, paraadnexal cysts, ovarian pregnancies,
      ovarian abscess. There is a great diversity of ultrasonographic patterns for a
      same histological type, specially for functional cysts and borderline tumors.
      Laparoscopic exploration has misdiagnosed two cancers and 10 borderline tumors
      and considered wrongly as suspects 19 benign lesions. 714 procedures have been
      led to term by laparoscopy, 89 have been ended by laparotomy, 26 for suspicion of
      malignancy and 50 for dissection failure. 27 postoperative complications have
      been counted among which 2 grafts on trocard sites after non protected extraction
      of one dermoid cyst and one borderline tumor. CONCLUSION: ultrasonographic
      appearance could not predict reliably the organic or functional nor benign or
      malignant character of an adnexal mass. Even careful laparoscopic examination can
      underestimate early stage ovarian cancer or borderline tumors. When diagnosed
      during or after laparoscopic procedure an ovarian cancer should always be managed
      by laparotomy. On the other hand, some borderline tumors can be treated by
      exclusive laparoscopy. When malignancy is suspected, an adnexectomy can be
      performed laparoscopically as a biopsy and allows a quick and appropriate
      treatment after paraffin-embedded sections. Both intraperitoneal and
      transparietal techniques have a minimal morbidity and allow a feasibility of more
      than 90%. The management of postmenopausal ovarian tumors differs only by the use
      of systematic oophorectomy if surgical procedure is indicated.

PMID- 9156712
TI  - [Evaluation of fertilizing ability of sperm in vitro].
AB  - For the study of 145 semen samples in an IVF program, a discriminant analysis
      allowed to calculate a score, including 8 parameters, able to predict up to 83%
      of IVF results.

PMID- 9156711
TI  - [Application prospects of structure-function studies of gonadotropins].
AB  - The study of the respective roles of the polypeptide and oligosaccharide parts of
      gonadotropins in their biological activities has been undertaken for many years
      through chemical and enzymatic modifications of natural hormones, expression of
      wild-type and mutated recombinant hormones and synthesis of active peptides. The
      present paper proposes a short summary of the future application prospects of
      these studies as undertaken in our laboratory.

PMID- 9156713
TI  - [Pelvic actinomycosis abscess and intrauterine device].
AB  - A case of association between IUD and a left tubal actinomycotic abscess is
      presented. The 45 year old patient was wearing an IUD for five years. The
      symptomatology was mainly that of pelvic pain with an associated mass in the left
      iliac fossa. The working diagnosis was that of a digestive tumor or an adnexal
      mass. The surgical procedure allowed to identify an inflammatory reaction with a
      pseudotumoral abscess formation in the left fallopian tube. The etiology was
      confirmed by the pathology and bacteriology reports. Treatment consists in
      surgical extirpation of the infected structures and long term antibacterial
      therapy. Actinomycosis is a rare but potentially serious pelvic disease. It may
      involve various organs and readily takes on the aspect of tumor formation.

PMID- 9156714
TI  - [Sex behavior of patients attending a free, anonymous HIV screening center in
      Paris].
AB  - People's sexual behavior changes as they acquire knowledge od HIV infection.
      During a 10-week period (September-November 1994), we analysed the results of
      interviews conducted prior to free, anonymous tests in the Figuier HIV screening
      center (CDAG, Paris). Men accounted for 61% of the 1275 attendees, and 62% were
      aged between 20 and 29 years (both sexes). Consultants were homo/bisexuals in 26%
      cases and 23% had an HIV-infected partner. Male and female hetero-sexual
      represented respectively 35 and 38% of attendees, and 1.7% had an HIV-infected
      partner. Most of the subjects (76%) had had more than one sexual partner in the
      last 12 months. 72% of the homo/bisexuals of all ages stated that they used
      condoms systematically during sexual penetration, compared to 35% of the
      heterosexuals. In contrast, only 3.9% of homo/bisexual used condoms during oral
      intercourse. 12% of the subjects (21% of homo/bisexuals, and 8.5% of
      heterosexuals) stated that they had been treated for an STD during the previous
      year, and most were aged between 25 and 34 years. The most frequent stated STDs
      were anogenital papillomavirus and herpes virus infections, and chlamydial
      infections. 80% of the homo/bisexual considered they "too a risk" (oral
      intercourse), compared to 47% of heterosexuals. 10% of the subjects did not
      collect their result. In this study the seroprevalence of HIV was 1%, with the
      highest values in the 25-34 year age group and among homo/bisexuals (3%), and the
      lowest values among male and female heterosexuals (0.4% and 0.2%, respectively).
      Most of the subjects, on the basis of their stated sexual behavior, were aware of
      the risk of HIV infection, but the high frequency of STDs shows that prevention
      campaigns must be reinforced. Practician must offer advice on prevention and
      screening in order to reduce the frequency of infective and tumoral diseases due
      to sexually transmitted pathogens.

PMID- 9156715
TI  - [Oocyte donation: ethical aspects related to the donor].
AB  - This paper analyses the reasons that brings couples to apprehend very differently
      the oocyte and sperm donation and highlights the difficulty of donor recruitment
      in those programs. The various types of donors (occasional, relational, IVF
      patient and professional) are described with their motivations, resistances,
      advantages and disadvantages. The contradictory consequences between free or paid
      donation, the particular risks of eggs donation (in comparison to sperm donation)
      for the donor as for the recipient are also highlighted. The problem of anonymity
      is also analysed in ethical terms but also in terms of technical efficacy: it is
      shown that anonymity, by authorizing sharing oocytes between recipients increases
      treatment efficacy by avoiding wasting this rare and precious resource of oocytes
      offered as a donation.

PMID- 9156716
TI  - Proceedings of the joint meeting of the European Society of Pediatric Allergy and
      Clinical Immunology (ESPACI) and the Paediatric Assembly of the European
      Respiratory Society (ERS). Odense, Denmark, May 22-25, 1996.

PMID- 9156717
TI  - Impact of viral infection on bronchial hyperresponsiveness.

PMID- 9156718
TI  - Prevention of allergic disease. Exposure to food allergens and dietetic
      intervention.

PMID- 9156720
TI  - Role of exposure to inhalant irritants and infections for the development of
      allergic diseases.

PMID- 9156719
TI  - Exposure to indoor inhalant allergens.

PMID- 9156721
TI  - Strategies for the prevention of atopic asthma.

PMID- 9156722
TI  - Impact of allergen exposure on bronchial hyperresponsiveness.

PMID- 9156723
TI  - Impact of treatment on bronchial hyperresponsiveness.

PMID- 9156724
TI  - Assessment of bronchial hyperresponsiveness in preschool children: methodological
      issues.

PMID- 9156725
TI  - Measurement of bronchial responsiveness by non-pharmacological challenges:
      methodological issues.

PMID- 9156726
TI  - Clinical relevance of bronchial hyperresponsiveness.

PMID- 9156727
TI  - Bronchial hyperresponsiveness from infancy to adulthood: epidemiological aspects.

PMID- 9156728
TI  - Epidemiology of food allergy.

PMID- 9156729
TI  - Atopic dermatitis: an increasing problem.

PMID- 9156730
TI  - Epidemiology of asthma: ISAAC--International Study of Asthma and Allergies in
      Childhood.

PMID- 9156731
TI  - Epidemiology of allergic rhinitis.

PMID- 9156732
TI  - Mechanisms of airway inflammation in cystic fibrosis.

PMID- 9156733
TI  - Cystic fibrosis and allergy.

PMID- 9156734
TI  - Bronchial hyperresponsiveness: definition and terminology.

PMID- 9156735
TI  - Anti-inflammatory therapy in cystic fibrosis.

PMID- 9156736
TI  - Genetic studies of cystic fibrosis and atopic asthma: current approaches and
      future aspects.

PMID- 9156737
TI  - Respiratory problems in the immune-compromised host.

PMID- 9156738
TI  - Respiratory syncytial virus immunology.

PMID- 9156739
TI  - Immunology of non-viral respiratory tract infections.

PMID- 9156740
TI  - How do we define the high-risk groups for development of allergic disease?

PMID- 9156741
TI  - Prenatal sensitisation.

PMID- 9156742
TI  - [Morphological criteria of the intensity of degranulation in free and fixed
      tissue mast cells depending on its type].

PMID- 9156743
TI  - [Once more on integration, only for real].

PMID- 9156744
TI  - [Technical means in the study of the structure of the human being].

PMID- 9156745
TI  - [The Siberian embryology school].

PMID- 9156746
TI  - [The reactions of different sections of human embryonic neuroepithelium to damage
      to the ventricular surface during explantation].
AB  - Fragments of different regions of brain, spinal cord and retina obtained from 6
      up to 7 wk human embryos were placed into media 199. On 24th hr of cultivation
      multiple invaginations developed in the explant ventricular surface as a response
      to its damage while preparing to explantation. Maturity extent of neural and
      glial elements was not essential to invagination intensity. Fragments of tectum
      and retina that are characterised by permanent shape of ventricular surface
      displayed minimal activity. These data suggest that the reaction considered
      reflects a property of neuroepithelial cells that constitutes an important factor
      in normal brain morphogenesis.

PMID- 9156747
TI  - [The ultrastructure of the synapses in the upper layers of the cat cerebral
      cortex after applying strychnine].
AB  - Ultrastructure of axo-dendritic and axo-spinous synapses in upper layers of cat
      brain gyrus suprasylvii was studied in 10, 30 and 90 min application of 0.1%
      strychnine nitrate and also 2.5 and 5 hrs after 90 min long use of strychnine.
      Portion of active synaptic contacts was found to grow higher in 10 and 30 min
      application and smaller during and 2.5 hrs after 90 min application. However,
      synaptic vesicles number is sharply reduced beginning from min 30 of application
      and only on 5th postapplication hr reaches initial level. Application of
      strychnine does not cause changes in synapse active zone length and presynaptic
      terminals section area. Reorganisations in pre- and postsynaptic terminals most
      acutely manifested in 90 min application are reversible--on 5th postapplication
      hr synapse ultrastructure turns into similar to that of control material.

PMID- 9156748
TI  - [The structure of the higher sections of the motor system in the rat brain after
      different forms of hypokinesia].
AB  - Composition of structural elements and different types of glial cells of caudate
      nucleus head were studied after 40, 90 and 120 days of intensive and 90 days of
      non-stress hypokinesia. In small portion of neurons and synapses non-stress
      hypokinesia causes changes basically indicating their low activity while
      intensive hypokinesia leads to more significant disorders. Motor area retains
      almost normal structure in both forms of influence. Decrease of spine number and
      variability is characteristic. Number of neurons with satellites and separate
      satellite forms in intensive hypokinesia significantly increases in different
      cortical layers. Oligodendrocyte and astrocyte number grows appropriately in
      surface and deep layers.

PMID- 9156749
TI  - [The formation of the choroid plexus of the human hindbrain].
AB  - This research was performed in 23 6-9 wk human embryos and was designed to study
      the process of formation of choroid plexus in telencephalon. Stage-to-stage
      characteristics of development of epithelium and stromal connective tissue in
      choroid plexus was given.

PMID- 9156751
TI  - [The structural bases of the tensile strength properties of nerves].
AB  - Morphological and mechanical properties of phrenic and vagal nerves cervical
      regions were studied in 51 cadavers of fetuses and newborns in 28 to 40 weeks
      gestation. Diameter and thickness of coats, porting of cross section area
      occupied by connective tissue and general tensile strength were found to increase
      in both nerves with the gestation period growth, while relative share of nerve
      bundles cross section reduces. Within the last trimester of intrauterine
      development nerve trunk rigidity grows smaller and tensile strength does not
      change significantly. Vagal and phrenic nerves possess an elongation reserve,
      safe for their structure due to nerve fibers tortuosity. Connection between the
      nerve trunk rigidity coefficient and epineurium thickness, porting of cross
      section of nerve and connective tissue is non-linear and statistically
      significantly approximates with hyperbolic equation of order 1 or 3.

PMID- 9156750
TI  - [Interneuronal interrelationships in autonomic ganglia (the ultrastructural
      aspects)].
AB  - Ultrastructural and immunocytochemical results of studies on interneuronal
      relationship in vegetative ganglia were represented. Age-related changes of
      synapses (appearance of synaptic type vesicles and smooth endoplasmic reticulum
      cisterns in postsynaptic terminals), peculiarities of interneuronal links in
      neurons containing neuropeptide Y and NO-synthase and structural manifestations
      of non-synaptic interneuronal links were shown. Modern views on interneuronal
      communications were discussed.

PMID- 9156752
TI  - [The monoaminergic innervation of the mediastinal pleura in human fetuses].
AB  - Mediastinal pleura was studied in pregnancy second part abortive human fetuses
      using histological and histochemical technique. It was found to have a well
      developed monoaminergic apparatus that includes adrenergic axons and mast cells.
      Electron microscope study confirmed monoaminergic and single peptidergic vesicles
      presence in axons. Luminescent method revealed that mast cells of nerve plexuses
      and blood vessels contain catecholamines and indolalkylamines. Monoaminergic
      axons and mast cells were shown to constitute a functionally integrative
      apparatus that regulates local hemodynamics and trophics.

PMID- 9156753
TI  - [The regeneration patterns of the canine hypogastric nerve when transplanted into
      the wall of the large intestine].
AB  - Findings of the study on the dog hypogastric nerve regeneration after
      implantation in caudal large intestine distal region are presented. Not only
      occurrence of the implanted nerve structure repair was shown, but also its
      assistance to formation of a well-developed neurovascular plexus in large
      intestine wall. Regenerated nerve fibres from the nervous plexus that forms in
      the epineurium of the implanted nerve invade the wall of large intestine. These
      data indicate the formation of an intramural nervous apparatus in large intestine
      wall providing additional neurotrophic regulation of an organ.

PMID- 9156754
TI  - [The ultrastructure of the neuromuscular synaptic terminal in the frog after
      denervation].
AB  - Ultrastructure of certain myoneural terminals were studied on serial sections on
      day 3, 5 and 8 after denervation. Ultrastructure of the terminal proximal and
      distal regions and Schwann cell were studied by means of morphometry and
      reconstruction of single terminals. On day 3 after denervation Schwann cell is
      activated in terminal proximal regions more rapidly than in distal ones with
      contractility in the terminal proximal region being more significant than in
      distal. On day 5 after denervation changes cover both initial and terminal
      regions and on day 8 almost all the regions where terminal were placed earlier
      were occupied with Schwann cell. A suggestion is made that structural changes in
      the Schwann cell-terminal system are the major contributors to decrease of
      synaptic discharge in early stages of denervation and appearance of Schwann cell
      potentials in more late ones.

PMID- 9156755
TI  - [The morphogenesis of the retinal neural layer and of the optic nerve in the
      normal white rat and under the action of large doses of x-ray irradiation during
      prenatal ontogeny].
AB  - Development of retina nerve layer and optic nerve were studied in 50 embryos and
      fetuses of albino rat in normal embryogenesis and in 55 embryos affected by large
      doses of X-ray irradiation (2.24 Cy) on d 10-14 of pregnancy (second critical
      period-a period of placentation and organogenesis). Main regularities in the
      development of the structures studied were demonstrated in intact fetuses. In the
      experiment the progeny subjected to X-ray irradiation showed basically bilateral
      abnormalities in development of retina nerve layer, optic nerve and its coats.

PMID- 9156756
TI  - [The morphofunctional organization of the accessory olfactory organ in mammals].
AB  - The study was performed in 180 fetuses of albino rat aged 12-21 d, cat--5-120 mm
      parietococcygeal length and man--4-70 mm parietococcygeal length, divided into
      histological slices. Vomeronasal organ of mammals, human included was found to be
      closely connected with nasal cavity, being its derivative. Within the period of
      primary palate formation in animals vomeronasal organ opens up into primary
      choanae, being linked both with oral and nasal cavities in similar extent. In
      following stages of development the period of secondary palate formation
      vomeronasal organ displays specific features of its structure.

PMID- 9156757
TI  - [Individual variability in the topography of the thoracic duct and its
      significance for the treatment of chylothorax by a video endosurgical method].
AB  - A possibility for clipping the ends of the damaged thoracic duct in chylothorax
      treatment by video endosurgical method was supported by the experiment performed
      in 10 dogs and topographoanatomical study carried out in 158 corpses of adults.
      The correlation found allows to forecast the possible position of thoracic region
      of the thoracic duct both by the thoracic cage shape and topography of the
      adjacent large anatomic elements.

PMID- 9156758
TI  - [The dorsal motor nucleus of the vagus nerve and its role in innervating the
      digestive tract].
AB  - Findings on topography of dorsal motor vagal nucleus neurons from which axons
      towards functionally different regions of digestive tract extend were analysed.
      Based on that and on the data available in literature main peculiarities of these
      cells topical organization were formulated. It is noted that "gastrointestinal"
      neurons are localised in dorsal motor nucleus as narrow stripes oriented caudo
      rostrad. Stripes (or columns) of neurons from axons towards the digestive trace
      different parts arise do not cross. Digestive tract oral parts receive
      parasympathetic efferent inputs from neurons of medial and dorsomedial parts of
      the nucleus and caudal--from ventromedial cells of dorsal motor nucleus. Sites of
      maximal accumulation of initial "gastrointestinal" neurons that occupy an area
      within +0.5-(+)2.0 mm of functionally different regions of stomach and gut were
      demonstrated in cat and rat.

PMID- 9156759
TI  - [The morphofunctional characteristics of connective tissue regeneration in the
      rat dermis after a gunshot injury].
AB  - Gunshot injury causes a complex of changes in perinecrotic area covering all
      tissue structures of skin which is discussed as a systemic organ disintegration,
      including disintegration of dermal differons. Connective tissue regeneration is
      reflected by a determined process. Replacement of a defect with granulation
      tissue should be considered as a reparative regeneration. Peculiarities of
      fibroblasts proliferation and differentiation in perinecrotic area indicate the
      prevalence of regenerative histogenesis features.

PMID- 9156760
TI  - [The smooth muscle tissue of the bronchi (histogenetic characteristics)].
AB  - Formation of bronchial smooth muscular tissue was studied in embryos, newborns
      and mature rats using electron microscopy, cellular dissociation, morphometry and
      cytophotometry. Ultrastructural and morphometrical characteristics was given for
      developing and mature smooth myocytes. Growth of heteromorphy was demonstrated in
      bronchial wall smooth myocytes in postnatal histogenesis. This allowed to
      distinguish subpopulations of small, medium and large cells that vary in linear
      parameters, nuclear-cytoplasmic ratio, nuclear ploidy and amount of summary
      proteins. These data allow to discuss definitive smooth muscular tissue of
      bronchi as an integrative differon.

PMID- 9156761
TI  - [Changes in the size of the stomach and its sections in human early postnatal
      ontogeny].
AB  - The present study represents findings of the examination of change dynamics in
      dimensions of human stomach and its regions since birth up to the age of 6
      months, carried out in cadavers of 40 children using methods of parametric and
      nonparametric statistics (newborns, below 2 months of age, 2-4 and 4-6 months)
      according to the results of relative and absolute dimensions of measurements.
      Differences in parameter growth for anatomical regions of stomach were found.
      Heterochronous pattern of the stomach (cardial and pyloric) regions increase were
      found together with the presence of 2 (2 and 4-6 months) periods of intensive
      growth and the period of the delayed growth (2-4 months).

PMID- 9156762
TI  - [The endocrine apparatus of the epithelium of the gastric mucosa in the steppe
      turtle (Testudo horsfieldi)].
AB  - Endocrinocytes of stomach mucosal epithelium were studied using light and
      electron microscopy in steppe turtle (Testudo horsfieldi). Endocrine apparatus of
      stomach in turtle was shown to retain the pattern characteristic for other
      representatives of vertebrates. Difference is observed in endocrinocytes
      localization. The latter are accumulated predominantly in upper and middle
      regions of glandulae, sometimes being encountered also in surface epithelium. 8
      cell types were identified according to size and structure: EC, G, D, D1, A-like,
      X, ECL and P. Relating to glandular lumen, endocrinocytes are divided into
      elements of closed (D, D1, A-like, ECL, X, and P) and open types (EC, G). In the
      latter apico-basal differentiation is expressed in cytoplasmic structure.
      Endocrinocytes are unevenly distributed throughout the stomach regions. Greatest
      number is concentrated in pyloric part, EC-cells being the predominant type. EC,
      ECL-cells and less A-like and D-cells are mostly encountered in fundal part, EC,
      G and single D and P cells--in pyloric part and, agranular and exo-endocrine
      cells--in both stomach parts.

PMID- 9156763
TI  - [Changes in the placenta of the elk Alces alces L. during pregnancy (morphometric
      research)].
AB  - Elk placentomes were studied during different stages of pregnancy using
      morphometry and optico-structural computerised analysis. Histological sections
      and smears from the surface of placentome section were made for that. Placentome
      were obtained from animals subjected to legal shooting in hunting districts of
      Novosibirsk. The attention was focused on the examination of cellular elements
      that constitute a trophoblastic lining and on distribution of capillaries
      maximally close to trophoblast in chorion villi. Diplokaryocytes are the
      predominant cellular population among the giant trophoblastic cells. The process
      of trophoblastic elements migration oriented to maternal organism tissues was
      described during the entire gestation period since month 3 to 8. Small placentome
      appearance on month 7 of pregnancy is considered for the manifestation of
      placental accessory compartments formation within the period of more intensive
      growth of the fetus body weight.

PMID- 9156764
TI  - [The formation of a distraction regenerate in the experimental modelling of the
      shape of the spinal canal].
AB  - The process of distractive regenerates of the vertebral arch was studied
      histologically in mature outbred dogs in modelling of vertebral canal by G. A.
      Ilizarov technique. During the process of distraction regenerate was shown to
      have a zonal structure i.e. to include 2 bone regions and connective tissue
      layering. Its growth is based on the fibers of that layering. The possibility of
      the increase of vertebral canal sagittal diameter up to 90-100% within 2-2,5
      months due to the formation of vertebral arch distractive regenerates is
      supported by the results of present study and opens the perspective of this
      technique use in clinical practice.

PMID- 9156765
TI  - [A method for the topographic anatomical study of the fourth ventricle in
      relation to the structures of the cranial base and vault].

PMID- 9156766
TI  - A relationship between TGF-beta 1 or IL-6 plasma levels and clinical features of
      spondyloarthropathies.

PMID- 9156767
TI  - [Acute chemical poisoning of humans as a medico-ecological problem].
AB  - Anthropogenic acute chemical exposures have become an important socioeconomic and
      environmental factor on the national, regional and global level. They present an
      actual or potential danger to vital activity and health of large population
      groups and normal operation of the Biosphere and natural components. Hence a
      problem of prevention and elimination of acute technogenic exposures hazardous
      for human health has expanded beyond the medical competence and grown to a major
      environmental issue.

PMID- 9156768
TI  - [Importance of dietary calcium in adaptation to combined stress in regions of the
      Far North].
AB  - The authors studied influence of calcium included into ratio on rat's antioxidant
      system functioning in experimental activation of lipids peroxidation. The results
      prove decompensation of enzymatic and non-enzymatic units of antioxidant system,
      both with normal and deficient calcium. At the same time, higher calcium intake
      resulted in adequate cellular adaptation to peroxidation.

PMID- 9156769
TI  - [Prevalence of dyslipoproteinemia in workers engaged in the production of higher
      fatty alcohols].
AB  - To reveal serum serum lipoprotein disorders, the authors studied serum lipids and
      lipoproteins compositions in 116 male workers engaged into production of higher
      fatty alcohols at oil-processing plant. All the cases of serum lipoprotein
      disorders were divided into 8 types. Secondary are the disorders of those
      examines (63.8%) who have chronic diseases. Six types of the disorders were
      identified in apparently healthy examines (36.2%).

PMID- 9156771
TI  - [Cause of death of the working-age population of Ufa in relation to the area of
      residence].
AB  - Two districts, one with developed oil-processing and petrochemical industries and
      administrative one, were selected in Ufa city for 20-year study of mortality
      among able-bodied population. Both districts demonstrated a decreasing share of
      able-bodied people in mortality structure. However, mortality of able-bodied
      population in the industrial district tended to increase, in the administrative
      one--to decrease. The main death causes were traumatism, cardiovascular diseases,
      malignancies. Mean age at death among the able-bodied population was lower in the
      industrial district, among the people engaged into oil-processing and
      petrochemical industries, transport and building sector.

PMID- 9156770
TI  - [Evaluation of the effects of a complex of physical factors on the functional
      state of men doing mental work].
AB  - The article evaluates influence of environmental, physical factors (noise,
      vibration, ambient temperature, illumination) on human functional state. The
      study involved 3 males performing mental tasks (following the object movements on
      monitor and correcting the track after variable interferences appearing in uneven
      time intervals) in specific microclimate chamber. The study revealed physiologic
      parameters more substantial for human functional state if influenced by
      environmental physical factors. For each parameter of human functional state and
      environmental physical factor a significance share was determined. If significant
      (r = 0.82, p < 0.001), correlations between parameters of human functional state
      and environmental physical factors became a material for integral equations.
      Method of cluster analyses defined 3 classes of human functional state and
      environmental status. Evaluation and regulation of those integral parameters
      became possible through a probability nomogram obtained.

PMID- 9156772
TI  - [Substantiation of the regulation of environmental heat load for workers exposed
      to heating microclimate (for example, steel smelting)].
AB  - The article analyzes the studies concerning long-term influence of heating stress
      on health state of subjects working in heating microclimate. Using epidemiologic
      cohort studies, the authors evaluated level and causes of mortality among workers
      of steel-making plant. Environmental heating was proved to increase
      cardiovascular mortality risk.

PMID- 9156773
TI  - [Epidemiological and etiopathological aspects of compression neuropathies of the
      lower limbs caused by adverse occupational factors (review of the literature)].

PMID- 9156775
TI  - [Elaboration and improvement of biochemical methods in early diagnosis and
      prognostication of the development of occupational diseases].
AB  - The article summarizes and analyzes scientific and practical studies conducted by
      Laboratory Department of Moscow Erisman Hygienic Research Institute. The
      theoretic works described resorption of Metallic ions from digestive tract into
      the blood, revealed mathematic dependence of resorption coefficient on ion radius
      and potential, hydration heat, solubility and other physical and chemical
      parameters. The scientists developed basic requirements for hazards detection in
      human biologic material during hygienic and toxicologic clinical investigations.
      A suggested bunch of biochemical and immunologic methods helps in early and
      differential diagnosis of respiratory diseases caused by dust. Refinements in
      some biochemical and toxicologic chemical methods enable to improve metrological
      characteristics, reduce reagents amount, simplify the methods.

PMID- 9156774
TI  - [Sensitization to industrial chemical allergens in bronchial asthma in children
      in environmental pollution].
AB  - Examination covered 41 children with bronchial asthma varying in severity, who
      live in ecologically hazardous industrial area. High incidence of sensibilization
      to industrial chemical allergens (chromium, nickel, formaldehyde and sometimes
      manganese and beryllium) appeared to be a feature of the examinees. Effect of IgE
      binding, a specific in vitro provocation test, identified pathogenic role of
      sensibilization to industrial allergens polluting environment. Clinical and
      immunologic principles revealed are basis for safe, specific and informative
      laboratory methods diagnosing sensibilization to industrial chemical allergens in
      ecologic, epidemiologic and clinical pediatric investigation.

PMID- 9156776
TI  - [Clinical and biochemical manifestations of the effects of nitro esters on
      workers].

PMID- 9156777
TI  - [Effects of chemical factors on health of the population in various regions of
      Russia].
AB  - Wide use of chemicals in agriculture is associated with higher morbidity among
      inhabitants of agricultural regions. Extreme increase of the morbidity is
      confined to the area subjected to releases of oil-processing and petrochemical
      enterprises and therefore results from combined exposure to agricultural
      chemicals and waste of oil-processing.

PMID- 9156778
TI  - [Complex evaluation of toxicity due to anthropogenic environmental pollution in
      ecologic ranking of the territory].
AB  - The authors studied possible use of screening cytogenetic methods calculating
      micronuclei in frog blood cells to indicate degree of environmental pollution and
      its danger for human health. The data correlate with higher incidence of
      reproductive disorders in the females and of congenital abnormalities in the
      children, who live in regions with higher microelements level in soil subjected
      to the cytogenetic studies. Biogeochemical screening study evaluating ecological
      situation by means of test-objects to be informative.

PMID- 9156779
TI  - The dorsal filament of the weakly electric Apteronotidae (Gymnotiformes;
      Teleostei) is specialized for electroreception.
AB  - The Apteronotidae, a family of weakly electric fish from South America
      (Gymnotiformes), possess a structure called the dorsal filament with an unknown
      function and evolutionary origin. This study compared the gross anatomy of the
      dorsal filament of 13 species of apteronotids and used light microscopy to
      examine the filaments of Adontosternarchus balaenops, Apteronotus albifrons, and
      Apteronotus leptorhynchus. The dorsal filament is an unscaled, thin, tapering
      structure attached to a mid-dorsal groove on the posterior half of the fish's
      back. The interior of the filament is a gelatinous mucopolysaccharide matrix
      (connective tissue) containing blood vessels and a bilateral nerve in which
      nearly all the afferents are large (8-10 mu m) and heavily myelinated. The
      location of the anterior origin of the filament varies from 0.48 to 0.66 of the
      body length, posterior to the snout, in 13 species. The filament is covered with
      hundreds of large-type tuberous electroreceptors and some ampullary receptors, at
      approximately the same density and ratio as those on the nearby back. The
      morphology of the large-type tuberous receptors and their afferents suggests that
      they are phase-coding T-units. A double layer of epithelial cells separates the
      ventral side of the filament from the groove in the trunk of the fish, except at
      the anterior origin where the interior of the filament is continuous with the
      body. This specialized double epithelium could provide a high resistance barrier
      to electrical current. This study was unable to distinguish between two
      hypotheses: that the dorsal filament is a modified adipose fin (as suggested
      previously), retained only in this family of Gymnotiformes; or that it is a
      uniquely derived character of the Apteronotidae.

PMID- 9156780
TI  - Activation of hypothalamic neurons by intraovarian pressure signals in a teleost
      fish, Clarias batrachus: role of mechanosensitive channels.
AB  - Application of intraovarian pressure is known to trigger profound
      cytomorphological changes in the neurosecretory cells of nucleus preopticus in
      the teleost Clarias batrachus. These findings indicate the presence of stretch
      receptors in the ovaries, perhaps equipped with mechanosensitive channels that
      transduce the stretch signals to be transmitted to the brain. To test the
      occurrence of the mechanosensitive channels in the ovaries, we administered a
      range of pharmacological agents (lignocaine, quinidine, tetraethylammonium
      chloride, ethylene-diaminetetraacetic acid and gadolinium) known to block the
      mechanosensitive ion channels, in the ovarian lumen prior to the administration
      of the intraovarian pressure. Pretreatment with the above agents inhibited the
      response by the nucleus preopticus neurosecretory cells to intraovarian pressure.
      The results suggest the occurrence of the mechanosensitive channels in the
      ovaries of teleostean fishes. In terms of function we speculate that the stretch
      sensory system and the ensuing pathway connecting the ovaries with the
      hypothalamus might play a role in apprising the brain of the status of ovarian
      maturity and in the initiation of the spawning reflex.

PMID- 9156781
TI  - Neuroanatomical and histochemical evidence for the presence of common lateral
      line and inner ear efferents and of efferents to the basilar papilla in a frog,
      Xenopus laevis.
AB  - The claimed absence of efferents to the basilar papilla in frogs was reexamined
      in Xenopus laevis with the use of acetylcholinesterase (AChE) histochemistry. We
      also tested the presence of common lateral line and inner ear efferents by
      employing neuroanatomical tract tracing techniques. Our data show some AChE
      positive fibers to the basilar papilla and all other sensory epithelia of the
      inner ear in larval and postmetamorphic frogs. Labeling of anterior lateral line
      and inner ear fibers with different fluorescing dextran amines resulted in a few
      double labeled efferent cells in the brainstem. Examination of the branching
      patterns of anterior lateral line efferents revealed collaterals to the inner
      ear, predominantly to the saccule and the lagena. In addition, two animals showed
      common efferents between the anterior lateral line and the basilar papilla. In
      derived anurans, such as ranids, which reportedly lack efferents to the basilar
      papilla, the basilar papillary afferents have a peripheral course that differs
      from that in salamanders and Xenopus. If such efferents are, indeed, absent, we
      propose that changed cues for pathway selection may have enabled only the
      afferents, and not the efferents, to reach the basilar papilla in derived frogs.

PMID- 9156782
TI  - Food storing and the hippocampus in Paridae.
AB  - Food storing passerines have a larger hippocampus, relative to the rest of the
      telencephalon and/or body mass, than do non-storing species. This study looked at
      the relationship between relative size of the hippocampus and degree of food
      storing in six species of Paridae (blue tit, Parus caeruleus, great tit, P major,
      marsh tit, P palustris, coal tit, P ater, black-capped chickadee, P.
      atricapillus, and willow tit, P montanus). The degree of storing by these species
      varies from little or none to thousands of food items. The period over which food
      is stored also varies from a few hours to several months. The results showed that
      hippocampal volume, relative to the rest of the telencephalon, is larger in those
      species that store more food, store for longer, or both. In an analysis of
      intraspecific variation within two of the species, the food storing marsh tit and
      the non-storing blue tit, there was a significant positive relationship between
      hippocampal volume relative to body mass, and telencephalic volume relative to
      body mass, in the marsh tit but no relationship between these variables in the
      blue tit.

PMID- 9156783
TI  - Evidence for GAP-43 within descending spinal axons in the North American opossum,
      Didelphis virginiana.
AB  - We have shown previously that GAP-43, a growth associated protein
      characteristically present in growing and regenerating axons, is relatively
      abundant in the spinal cord of adult opossums. In the present study, we combined
      the orthograde transport of the fluorescent marker Fluoro-Ruby with
      immunofluorescence for GAP-43 to determine if any of it is present within
      descending spinal axons. When Fluoro-Ruby was injected into the red nucleus and
      midbrain tegmentum, the medial pontine or medullary reticular formation, the
      medullary raphe or the lateral vestibular nucleus, axons were labeled in the
      expected areas of the spinal cord, but in most cases none showed evidence for GAP
      43. In two of the four cases with rubral injections, however, a few labeled axons
      within the rubrospinal tract showed GAP-43 immunofluorescence, and in one case
      with an injection of the gigantocellular reticular nucleus and adjacent raphe,
      labeled axons within lamina IX immunostained for the protein. Since
      serotoninergic neurons are present within the gigantocellular reticular nucleus
      and adjacent raphe, and axons of the same phenotype are abundant within lamina
      IX, we asked whether serotoninergic axons contain GAP-43. When sections of the
      spinal cord were immunostained for both serotonin and GAP-43, many axons within
      lamina IX showed evidence for both substances. Such axons appeared to contact
      presumptive motoneurons. In cases with Fluoro-Ruby injections of the forelimb
      motor cortex, labeled axons were present within the pyramidal tract, and some of
      them showed evidence for GAP-43.

PMID- 9156784
TI  - Neurological and osteological definitions of cervical vertebrae in mammals.
AB  - The presence of seven cervical vertebrae is an almost universal mammalian trait.
      The posterior boundary of the cervical series is traditionally defined
      osteologically, but its location is also predictable using neurological markers
      of the brachial plexus. The existence of three living mammalian genera with
      osteologically defined cervical counts other than seven offers the opportunity to
      examine the coincidence of osteological and neurological definitions of the term
      'cervical'. Despite variations in rib and articular processes of cervical
      vertebrae dissections of the brachial plexuses of these genera reveal that
      neurological and osteological markers of the cervical series define the same,
      nontraditional, posterior boundaries of the series. Subdivision of the
      predetermined cervical mesoderm into a nontraditional number of segments has not
      altered the relationship of the limb or its innervation to the cervical/thoracic
      boundary. This nontraditional subdivision appears to have evolved separately at
      least three times.

PMID- 9156785
TI  - Treatment with the platelet-activating factor antagonist TCV-309 in patients with
      severe systemic inflammatory response syndrome: a prospective, multi-center,
      double-blind, randomized phase II trial.
AB  - In a prospective randomized, double-blind, placebo-controlled clinical study, the
      safety and efficacy of the platelet-activating factor antagonist TCV-309 in the
      treatment of systemic inflammatory response syndrome was studied. In total 29
      patients were treated with 1.0 mg/kg TCV-309 twice daily during 7 days or with
      placebo. Study parameters were as follows: adverse events, 28 and 56 day all
      cause mortality, multi-organ failure scores, and the inflammatory mediators tumor
      necrosis factor, interleukin 6, interleukin 8, and soluble E-selectin. There was
      no difference in number and severity of adverse events between TCV-309- and
      placebo-treated patients. Day 28 and day 56 mortality was similar in both groups
      (day 56: 7/12 TCV-309 vs. 9/16 placebo, NS). Pulmonary and hematological failure
      scores improved significantly in TCV-309-treated patients (p < .05). There was no
      difference in inflammatory mediator levels between TCV-309- and placebo-treated
      patients. Treatment with TCV-309 appears to be safe in patients with systemic
      inflammatory response syndrome and does improve organ failure significantly.

PMID- 9156786
TI  - Heat shock protein expression in human placenta and umbilical cord.
AB  - We examined the level of heat shock proteins (HSPs) present in umbilical cord
      vessels and placenta following delivery. A 10 cm segment of fresh umbilical cord
      was obtained immediately after delivery and a placental biopsy was obtained
      following the third stage of labor. Apgar scores, cord pHs, and pertinent
      histories were recorded. Tissues were prepared and analyzed for HSP mRNA by in
      situ hybridization, Western blot, and immunohistochemistry. Sixteen patients were
      studied. HSP72 mRNA was selectively expressed in the vascular smooth muscle in
      all cord arteries and veins. This correlated with marked expression of HSP72
      protein in the vascular media. Both HSP72/73 mRNA and protein expression were
      noted diffusely in the placenta. HSP27 protein was highly expressed in umbilical
      cords with lower levels present in placentas. There were no correlations between
      method of delivery, gestational age, Apgar score, cord pH, or fetal outcome to
      the magnitude or distribution of the HSP response. This is the first
      demonstration of HSP expression in the human maternal-fetal circulation.

PMID- 9156787
TI  - Zonal heterogeneity of hepatic injury following shock/resuscitation: relationship
      of xanthine oxidase activity to localization of neutrophil accumulation and
      central lobular necrosis.
AB  - Post-ischemic hepatic injury is characterized by zonal heterogeneity of injury
      (central lobular necrosis), sinusoidal neutrophil accumulation, and injury
      generated by reactive oxygen metabolites. We evaluated the role of the
      heterogeneous distribution of hepatic xanthine oxidase in the generation of
      neutrophil accumulation and consequent hepatocellular injury in rats subjected to
      shock [controlled hemorrhagic hypotension (mean arterial pressure = 37.5 + or -
      2.5 mmHg for 120 min)], with or without subsequent resuscitation and hemodynamic
      stabilization, compared with sham-operated rats. Shock/resuscitation produced
      striking neutrophil accumulation (assayed by esterase histochemistry) in the
      pericentral sinusoids, associated with centrolobular necrosis. This paralleled
      the pericentral distribution of xanthine oxidase (determined by histochemical
      assay of frozen sections) and its release from the liver into the circulation at
      resuscitation. Pretreatment with allopurinol inhibited hepatic xanthine oxidase
      activity, neutrophil accumulation, and pericentral hepatocyte necrosis in
      shock/resuscitation in rats. These findings suggest that reactive oxygen
      metabolites generated by heterogeneously distributed xanthine oxidase may
      contribute to the heterogeneity of hepatocellular injury in "ischemic hepatitis."

PMID- 9156789
TI  - The role of nitric oxide in subcutaneous and transmural gut tissue oxygenation.
AB  - The influence of inhibiting the nitric oxide (NO) synthetase on tissue perfusion
      as indicated by tissue oxygen tensions was determined. Tissue oxygen probes were
      placed subcutaneously and on serosal and mucosal surfaces of colon of
      anesthetized adult rats. After a control period, the inhibitor of NO formation,
      N(G)-nitro-L-arginine methyl ester (L-NMMA), was given intravenously and followed
      20 min later by infusion of substrate for NO synthetase, L-arginine. Mean
      arterial blood pressure (MAP), subcutaneous tissue oxygen tension (P(SQ)O2),
      serosal tissue oxygen tension (P SO(2)), and mucosal tissue oxygen tension
      (P(M)O2) were simultaneously measured. Baseline values for the measured
      parameters were MAP = 95 + or - 9 mmHg, P(SQ)O2 = 61 + or - 7 mmHg, P(S)O2 65 +
      or - 7 mmHg, and P(M)02 = 9 + or - 2 mmHg. The infusion of L-NMMA induced a
      significant increase in MAP to 123 + or - 7 mmHg (p < .001) and P(SQ)O2 to 72 +
      or - 7 mmHg (p < .001). P(S)O2 did not change significantly from baseline after L
      NMMA infusion. A significant decrease in P(M)O2 to 4 + or - 2 mmHg was noted
      after L-NMMA infusion (p < .001). The administration of L-arginine promptly
      returned all measured parameters to baseline levels within 10 min of infusion. A
      transmural P(O2) gradient exists across the colon with P(M)O2 far lower than
      P(S)O2. P(SQ)O2 approximates P(S)O2 at baseline and P(S)O2 is not altered by
      inhibition of the NO synthetase. The 45% reduction in mucosal PO2 after L-NMMA,
      which was reversed by L-arginine infusion, suggests that nitric oxide
      participates in splanchnic vasomotor control with a preferential effect in the
      mucosal vasculature. The observed decrease in mucosal PO2 observed after
      inhibition of NO production is similar to the worsened hypoxia previously
      measured during hemorrhagic shock. Further work clarifying the local control
      mechanisms of gut tissue P02 can direct therapies to increase gut tissue
      oxygenation.

PMID- 9156788
TI  - Sepsis increases putrescine concentration and protein synthesis in mucosa of
      small intestine in rats.
AB  - Recent studies suggest that sepsis stimulates mucosal polyamine and protein
      synthesis. It is not known in which cell type polyamine biosynthesis is increased
      during sepsis and if polyamines regulate mucosal protein synthesis. We examined
      the effect of sepsis in rats on polyamine biosynthesis in isolated jejunal
      enterocytes and measured mucosal protein synthesis following inhibition of
      ornithine decarboxylase (ODC) activity with difluoromethylornithine. ODC and S
      adenosylmethionine decarboxylase (SAMDC) activities and putrescine concentrations
      were increased in isolated jejunal enterocytes 16 h after induction of sepsis by
      cecal ligation and puncture. Enterocyte spermidine and spermine levels were not
      influenced by sepsis. Mucosal ODC and SAMDC activities and polyamine levels were
      increased following treatment of rats with interleukin-1 but not tumor necrosis
      factor. Treatment of rats with difluoromethylornithine prevented the sepsis
      induced increase in mucosal ODC activity, putrescine concentration, and protein
      synthesis rate. The results suggest that sepsis increases ODC and SAMDC
      activities and putrescine concentrations in enterocytes of the small intestine.
      This metabolic response to sepsis may be regulated by interleukin-1 although
      other mechanisms may also be involved. Increased mucosal protein synthesis during
      sepsis may at least in part be regulated by increased putrescine levels.

PMID- 9156790
TI  - Hepatic release of tumor necrosis factor in the endotoxin-treated conscious dog.
AB  - The effects of a 4 h intraportal infusion of Escherichia coli lipopolysaccharide
      (LPS, .21 mu g/kg/min) on the release of tumor necrosis factor (TNF) by hepatic
      and nonhepatic splanchnic tissues was assessed in the chronically catheterized
      conscious dog (n = 7) using arteriovenous difference techniques. TNF levels were
      measured using both a WEHI-164 cytotoxicity assay (WEHI) and a h-TNF-alpha EIA
      kit (ELISA; Biosource, Camarillo, CA). Using WEHI, arterial TNF levels increased
      from 10 + or - 6 pg/mL to a peak of 4667 + or - 1442 pg/mL 100 min after LPS and
      fell to 443 + or - 199 pg/mL by 240 min. Using ELISA, arterial TNF levels
      increased from 5 + or - 5 pg/mL to a peak of 12,234 + or - 2046 pg/mL at  100 min
      and fell to 3511 + or - 991 pg/mL by 240 min. WEHI could not be used to assess
      organ TNF release due to excessive assay variability. Based upon ELISA, net
      hepatic TNF output increased from undetectable release at basal to 23.0 + or -
      10.7 ng/kg/min at 60 min and returned toward basal by 240 min (4.7 + or - 3.8
      ng/kg/min). Net release of TNF by the nonhepatic splanchnic bed was not observed.
      One compartment analysis of the arterial TNF response indicated that net release
      of TNF by the liver accounted for the majority of the increase in the arterial
      TNF levels. In summary, after intraportal LPS infusion, it was determined that 1)
      both assays predict similar qualitative TNF response, while the quantitative
      response differs, 2) the liver is the major site of TNF production, and 3) the
      nonhepatic splanchnic bed is not a net producer of TNF.

PMID- 9156791
TI  - Regional arteriovenous differences in P(CO2) and pH can reflect critical organ
      oxygen delivery during endotoxemia.
AB  - The goal of this study was to assess whether serial measurements of regional veno
      arterial PcoC2 (VAPco2) and arteriovenous pH (AVpH) differences reflect the onset
      of tissue hypoxia in various organs during endotoxemia. In 12 anesthetized,
      mechanically ventilated dogs, ultrasonic flow probes were placed around superior
      mesenteric, renal, and femoral arteries to measure regional blood flow. The
      corresponding veins were cannulated for blood sampling. Oxygen uptake (V02) was
      determined from exhaled gas analysis, and oxygen delivery (D02) was calculated as
      the product of thermodilution cardiac output and arterial oxygen content. Six
      dogs served as controls, and six received Escherichia coli endotoxin. Cardiac
      tamponade was induced to reduce D02. Systemic, mesenteric, and femoral critical
      D02 (DO2crit) were higher in the endotoxic than in the control group (systemic:
      12.1 + or - 2.2 vs. 7.9 + or - 2.6 mL/kg min; mesenteric: 8.2 + or - 2.5 vs. 4.1
      + or - .6 mL/100 g tissue-min; femoral: 8.3 + or - 2.3 vs. 4.6 + or - .9 mL/min;
      all p < .05). Systemic and regional critical oxygen extraction ratio (O2ERcrit)
      were lower in the endotoxic than in the control group (systemic: 45.1 + or - 9.7
      vs. 74.1 + or - 9.1%; mesenteric: 37.1 + or - 15.4 vs. 71.1 + or - 7.4%; renal:
      30.7 + or - 24.6 vs. 53.9 + or - 28.7%; femoral: 48.1 + or - 9.2 vs. 75.3 + or -
      6.9%; all p < .05). With and without endotoxin, systemic and regional DO2crit
      calculated from V02, VAPco2, or AVpH were similar. In conclusion, systemic and
      regional VAPco2 and AVpH gradients can reflect hypoxic threshold in the presence,
      as in the absence, of endotoxemia.

PMID- 9156792
TI  - Dose-response effect of in vivo administration of endotoxin on polymorphonuclear
      leukocytes oxidative burst.
AB  - In vitro, endotoxin primes polymorphonuclear leukocytes (PMNs) to respond with a
      greater oxidative burst. The purpose of the present study was to investigate the
      in vivo effect of a wide range of single endotoxin bolus doses using a rat model.
      PMNs were subsequently challenged in vitro with phorbol ester to produce reactive
      oxygen intermediates (ROI). Flow cytometric determination of ROI production by
      large doses induced a decrease in ROI production by the few PMNs that remained in
      the circulation. By 6 h after injection, ROI production had returned to basal
      levels after a high dose, and was still increasing after a low dose. Neutropenia
      occurred immediately after endotoxin injection. After 6 h, PMN counts returned to
      almost normal levels with a high dose, but rebound neutrophilia occurred with a
      small dose. In contrast to in vitro studies, in vivo injection showed a response
      pattern that varied widely with dose and time of observation.

PMID- 9156793
TI  - Nitric oxide synthase inhibition versus norepinephrine in ovine sepsis: effects
      on regional blood flow.
AB  - Hypotension is a serious problem in septic patients. We investigated regional
      perfusion in several organs during treatment of hyperdynamic sepsis in sheep.
      Sepsis was induced and maintained for the entire experiment with a continuous
      infusion of live Pseudomonas aeruginosa. Treatment with either norepinephrine or
      the nitric oxide synthase inhibitor L omega-mono-methyl-arginine (L-NMMA) was
      begun after 24 h of sepsis and continued for 24 h. The norepinephrine dosage was
      adjusted to achieve the same increase in mean arterial pressure as that obtained
      by a fixed dose of L-NMMA (7 mg/kg/h). Blood flows were analyzed by the
      microsphere technique. Both compounds restored blood pressure effectively, but
      only L-NMMA caused a significant increase in systemic vascular resistance,
      concomitant with a significant fall in cardiac output. Sepsis caused an increase
      in myocardial blood flow and a redistribution of blood flow away from the
      pancreas and the stomach. Renal blood flow was not significantly elevated. During
      treatment with either compound, renal blood flow remained unchanged, despite a
      fall in cardiac output in the L-NMMA group. Unchanged renal blood flow combined
      with the restoration of arterial blood pressure caused a significant increase in
      urine output. Both L-NMMA and norepinephrine caused a redistribution of blood
      flow to the colon. Pancreatic blood flow was further reduced by L-NMMA but the
      oxygen extraction improved simultaneously, so that oxygen availability in the
      pancreas might have been unchanged. Because ischemic pancreatitis in sepsis is
      likely to trigger multiorgan failure, further investigations in that area are
      desirable.

PMID- 9156794
TI  - Post-ischemic shunt following hepatic ischemia/reperfusion does not affect tissue
      chemokine levels of tissue injury.
AB  - Hepatic ischemia followed by reperfusion causes the release of a cascade of
      mediators, including tumor necrosis factor-alpha and epithelial neutrophil
      activating protein (ENA-78), which are important in the subsequent development of
      the lung and liver injury associated with this insult. We hypothesize that
      preferential post-ischemic shunting of blood into the nonischemic hepatic lobes
      at the time of reperfusion may increase the ischemic injury. To test this
      hypothesis, we utilized a rat model of lobar no-flow hepatic ischemia/reperfusion
      and removed the nonischemic hepatic lobes at the time of reperfusion to eliminate
      the preferential shunting of blood into the nonischemic tissues. We assessed
      pulmonary and hepatic tissue levels of ENA-78, pulmonary neutrophil influx and
      changes in pulmonary capillary permeability, and liver injury as measured by
      hepatic neutrophil influx and serum transaminase levels. Our results demonstrated
      that there were no significant differences in pulmonary and hepatic levels of ENA
      78, or in the development of the lung and liver injury in animals undergoing
      resection of the nonischemic hepatic lobes at the time of reperfusion, as
      compared with animals undergoing hepatic ischemia/reperfusion alone.

PMID- 9156795
TI  - Ultrastructural changes in skeletal muscle mitochondria in gram-negative sepsis.
AB  - Energy metabolism during sepsis is incompletely understood, but alterations in
      mitochondrial structure and function appear important. We measured time-dependent
      changes in mitochondrial structure during sepsis using serial skeletal muscle
      biopsies in anesthetized baboons injected with 10(10) CFU/kg of live Escherichia
      coli (LD(100)). Skeletal muscle biopsies were taken before bacterial challenge (0
      h controls) and at 12 h, 24 h, and death. By qualitative electron microscopy, the
      organelles became enlarged with distorted cristae and developed electron lucent
      areas within the matrix. With advanced injury the inner membrane became
      fragmented. Quantitative morphometric analysis showed a 50% increase in mean
      cristal membrane surface density by 24 h (p < .05) accompanied by a 100% increase
      in intermembrane space (p < .01). Matrix volume density decreased progressively
      (p < .01). These changes in mitochondrial ultrastructure occur within 12 h after
      the onset of the bacterial insult. This damage, including destruction or
      reorganization of both membrane and matrix proteins, is severe enough to
      compromise oxidative metabolism in muscle in Gram-negative sepsis.

PMID- 9156796
TI  - Partial hepatectomy reduces the endotoxin-induced peak circulating level of tumor
      necrosis factor in rats.
AB  - The pro-inflammatory cytokine tumor necrosis factor (TNF) is dramatically and
      transiently elevated in the circulation during endotoxic and septic shock and is
      a primary mediator in the pathogenesis of the sepsis syndrome. TNF peaks in the
      circulation 90 min after endotoxin administration with little variation, even
      among species. The specific cells, tissues, or organs that produce the high
      circulating level of TNF in septic shock remain unknown. The most likely sources
      are macrophage-laden tissues such as the liver and the spleen and circulating
      blood leukocytes. This study evaluated whether the liver is an important source
      producing the TNF spike 90 min after endotoxin. To test this hypothesis, we
      measured the peak circulating level of TNF following an endotoxin injection in
      rats subjected to a two-thirds hepatectomy versus sham-operated controls.
      Hepatechectomized rats produced 64% less TNF after endotoxin than controls (857 +
      or - 143 pg/mL plasma vs. 2410 + or - 491, respectively; p < .01). In contrast,
      splenectomy did not significantly after peak TNF levels versus sham-operated
      controls following an endotoxin injection (1380 + or - 148 pg/mL plasma vs. 1710
      + or - 291). Furthermore, incubation of rat blood with endotoxin for 90 min did
      not significantly increase TNF above controls. These experiments demonstrate an
      important role for the liver in producing the high circulating levels of TNF
      after an endotoxin injection and suggest that hepatic-specific cytokine
      modulation deserves study for a therapeutic benefit in septic shock.

PMID- 9156797
TI  - Hematopoietic stem cell gene transfer.

PMID- 9156798
TI  - Complete correction of hyperbilirubinemia in the Gunn rat model of Crigler-Najjar
      syndrome type I following transient in vivo adenovirus-mediated expression of
      human bilirubin UDP-glucuronosyltransferase.
AB  - Recombinant adenoviral vectors are useful for the in vivo expression of genes in
      hepatocytes. Adenoviral vectors deleted in E1a, E1b, and E3b were constructed and
      used to study in vivo expression of the major human bilirubin UDP
      glucuronosyltransferase isoform (HUG Br1) under the transcriptional control of
      the cytomegalovirus (CMV) immediate-early promoter-enhancer (H5.010CMV hugBr1).
      As a control, a recombinant adenoviral vector containing the beta-galactosidase
      reporter gene driven by the CMV promoter-enhancer was employed (H5. 010CMVlacZ).
      Recombinant virus was expanded following exposure to E1 transcomplementing (293)
      cells and concentrated to t titer of approximately 10(13) particles per
      milliliter. A rat model for Crigler-Najjar syndrome type I deficient in HUG Br1
      (ie the Gunn rat) was injected with 5 X 10(9) plaque-forming units (p.f.u.) via
      the portal vein of either H5.010CMVhugBr1 or H5. 010CMVlacZ. Rats from each set
      were killed at 3 days, 11 days and 22 days after infusion. Liver total cellular
      DNA, RNA and protein were analyzed for the transgene and the transgene product at
      the specified times. Analysis of livers by Southern blot hybridization
      demonstrates sequence-specific hybridization to adenoviral vector DNA, and
      Northern blot hybridization demonstrates sequence-specific hybridization to
      transgene-derived RNA. DNA levels peak at approximately one copy number at 3 days
      and decline over 22 days. RNA and Western blot analyses demonstrate
      overexpression of message and protein at 3 days, declining over 22 days. In virto
      functional assay for bilirubin glucuronosyl-transferase activity demonstrates
      overexpression of bilirubin UDP-glucurosyltransferase function. In situ
      hybridization of frozen sections to detect expressed mRNA using beta
      galactosidasederived 35S-labeled riboprobes demonstrates adenovirus-derived
      transgene expression in hepatocytes. Significant drops in serum bilirubin levels
      were noted following expression of HUG Br1 but not beta-galactosidase. The drop
      in serum bilirubin correlates with the appearance of bilirubin glucuronides in
      bile. In summary, recombinant adenoviral vectors were used to demonstrate in vivo
      complementation of the genetic defect in Gunn rat livers with the HUG Br1 cDNA
      leading to a resolution of hyperbilirubinemia lasting approximately 7 weeks.
      These studies suggest that delivery of the HUG Br1 cDNA might provide a
      reasonable therapeutic benefit for Crigler-Najjar syndrome type I patients, as
      safe and efficacious gene delivery systems are developed.

PMID- 9156799
TI  - Ex vivo gene delivery of platelet-derived growth factor increases 0-2A
      progenitors in adult rat spinal cord.
AB  - The O-2A progenitor cell, which serves as a stem cell for the myelinating
      oligodendrocyte, has been implicated as a major target for radiation-induced
      spinal cord injury. In an attempt to increase the number of O-2A cells in the
      spinal cord, we applied an ex vivo gene therapy procedure for delivering platelet
      derived growth factor (PDGF). Recombinant fibroblasts expressing PDGF A chain
      were injected into the cisterna magna of adult rats, which resulted in cell
      seeding of the subarachnoid space of the cervical spinal cord. The number of O-2A
      progenitors in the cervical spinal cord was then assessed with an in vitro
      clonogenic assay. O-2A cells were found to be increased 8 days after recombinant
      cell injection, and they remained elevated up to at least 14 days. Analysis of O
      2A colonies indicated that the implantation of PDGF-expressing cells increased
      the number of O-2A progenitors without affecting their in vitro proliferation
      potential or differentiation capacity. These data suggest that implantation of
      PDGF-expressing cells in the subarachnoid space of the cervical spinal cord may
      influence a stem cell population critical to the repair of demyelinated lesions.

PMID- 9156800
TI  - Condensation of plasmid DNA with polylysine improves liposome-mediated gene
      transfer into established and primary muscle cells.
AB  - Cationic liposomes provide a means to introduce genes into cells both ex vivo and
      in vivo. In the past few years their use has been described in several tissues,
      e.g. lungs, liver, endothelium, brain. In this study we evaluated a commercially
      available poly-cationic liposome formulation in delivering a reporter gene into
      cultured myogenic cell lines from mouse and rat, and primary fetal human
      myoblasts. We also examined the effect of serum on liposome-mediated transfection
      and designed a new procedure to enhance transfection efficiency, based on the pre
      condensation of plasmid DNA with polylysine. Polylysine pre-condensation was
      particularly effective when transfecting the cells in the presence of serum, a
      finding that could be significant for in vivo transfections.

PMID- 9156801
TI  - Gene transfer by naked DNA into adult mouse brain.
AB  - Nonviral gene transfer into the central nervous system could provide a basis for
      therapeutic uses and fundamental research. We show that naked DNA injected
      intracerebrally into the mouse brain can provide expression of a reporter
      protein. Expression is dose dependent, being maximal for 150 mu g DNA injected.
      We observed less than 5 days expression of the luciferase transgene, which is not
      improved with plasmid preparations virtually free of lipopolysaccharide. Thus,
      the adult brain behaves as striated muscle for naked DNA uptake and
      transcription, albeit at a much lower efficiency. In neither adult brain nor
      muscle did complexation of DNA with cationic lipid improve transgene expression.
      Double immunolabeling using cell-specific markers shows that both neurons and
      glia are transfected by naked DNA gene transfer methodology.

PMID- 9156802
TI  - Transient immune blockade prevents formation of neutralizing antibody to
      recombinant adenovirus and allows repeated gene transfer to mouse liver.
AB  - The hepatotropic properties of human adenoviruses have been used to develop
      vectors for in vivo liver-directed gene therapy. Current limitations for this
      vector system are the associated hepatitis that develops as a result of antigen
      specific cellular immune responses and the difficulty in accomplishing repeated
      gene transfer. This study uses mouse models to define immune responses of the
      recipient animal that have previously been shown to prevent successful re
      administration of virus and suggests approaches for preventing the development of
      these blocking immune responses. Our studies are most consistent with class II
      MHC-dependent activation ot T helper cells and B cells to capsid proteins of the
      input virus leading to the production of antiviral neutralizing antibody
      following a primary exposure to virus; this capsid-specific antibody appears to
      bind to virus and prevents entry in the context of a second administration of
      virus. Transient ablation of CD4 function at the time of virus administration
      prevents the formation of neutralizing antibody thereby allowing efficient gene
      transfer after at least two subsequent administrations of virus. Experiments in
      beta(2)m(-) mice and C57BL/6 mice treated with IL-12 suggested a more selective
      ablation of immune function based on inhibiting the activation of the T(H2)
      subset of T helper cells. From these studies on immune mechanisms it is hoped
      that viable strategies can be developed to overcome the problem of humoral
      immunity that occurs after the initial genetic therapy.

PMID- 9156803
TI  - Enhanced efficacy of combination of IL-2 gene and IL-6 gene-transfected tumor
      cells in the treatment of established metastatic tumors.
AB  - IL-2 and IL-6 are important cytokines which have potent antitumor effects and can
      cooperate to induce immune responses more effectively. IL-2 gene or IL-6 gene
      transfected tumor cells exhibited reduced tumorigenicity and decreased metastatic
      potential. In order to increase the therapeutic efficacy of IL-2 gene-, IL-6 gene
      modified tumor vaccines, the experimental pulmonary metastatic melanoma-bearing
      mice were treated with inactivated IL-2 gene-transfected tumor cells and
      inactivated IL-6 gene-transfected tumor cells. After the combined vaccination,
      the pulmonary metastases were reduced more significantly and the survival time of
      tumor-bearing mice was also markedly prolonged. The CTL activity, NK activity and
      IL-2-induced LAK activity, IL-2 and TNF secretion from the splenocytes of the
      above tumor-bearing mice increased more significantly than that of tumor-bearing
      mice vaccinated with IL-2 gene-transfected vaccine or IL-6 gene transfected
      vaccine alone. These results demonstrated that the combined use of IL-2 gene
      transfected tumor vaccine and IL-6 gene-transfected tumor vaccine could achieve
      more potent antitumor effect via more effective activation of specific and non
      specific antitumor immune responses.

PMID- 9156804
TI  - Episomal expression of wild-type CFTR corrects cAMP-dependent chloride transport
      in respiratory epithelial cells.
AB  - The isolation of the gene responsible for the Cl- ion transport defect in cystic
      fibrosis (CF) has provided important information about the relationship between
      the disease pathology and the underlying genetic and biochemical mechanisms. In
      addition, new areas of investigation and therapy are now possible. Most notably,
      the isolation of the CF gene, the cystic fibrosis transmembrane conductance
      regulator (CFTR) has been led to the development of different gene therapy
      strategies. To circumvent possible complications due to insertional mutagenesis
      and virally induced immune responses, we have employed Epstein-Barr virus (EBV)
      based expression vectors for correction of the cAMP-dependent Cl- transport
      defect associated with CF. A CFTR-containing expression construct under the
      regulation of the Rous sarcoma virus (RSV) long terminal repeat (LTR)
      (pREP5/CFTR) was introduced into transformed human airway epithelial cells
      defective in cAMP-dependent Cl-transport. Transfected cells were assayed for Cl-
      ion transport by (36)Cl- efflux, SPQ, and patch clamp and showed restoration of
      intact cAMP-dependent transport. CFTR transcription from pREP5/CFTR was detected
      by Northern hybridization. The level of response to agonists appeared to be
      dependent on the level of CFTR expression. When cells were tested for functional
      expression of CFTR after removal of selection pressure, they showed a continuous
      decrease in responsiveness to forskolin as a function of time after removal of
      selection. This decrease correlated with a loss of CFTR mRNA in the loss of the
      PREP5/CFTR. After 12 to 15 weeks growth without selection both cAMP-dependent Cl-
      transport and plasmid-derived CFTR mRNA were not detectable. However, it was
      still possible to rescue cAMP-dependent Cl- transport in these transfected cells
      by reselection suggesting the presence of the CFTR containing plasmid in a
      portion of the cells. Analysis of DNA indicated that the pREP5/CFTR vector copy
      number was reduced from 30 copies per cell with continuous selection, to
      approximately 0.3 copies per cell after 20 weeks without hygromycin B.

PMID- 9156805
TI  - Comparison of promoter strengths on gene delivery into mammalian brain cells
      using AAV vectors.
AB  - Recent reports have suggested that delivery of genes flanked by AAV ITRs may be
      useful for gene therapy of diseases that involve the brain. We have compared the
      efficiency of gene expression in vitro in CNS-derived cells from four different
      promoters when the transgene is flanked by AAV ITRs, using both transfection via
      cationic liposomes, and infection via rAAV. The human cytomegalovirus (CMV)
      immediate-early enhancer/promoter, the SV40 early enhancer/promoter, the JC
      polymovirus promoter, and the chicken beta-actin promoter coupled to the CMV
      enhancer were able to drive expression of the reporter gene beta-galactosidase in
      all tumor and primary brain cell cultures tested. Although the relative order of
      efficiency differed between cell types, the CMV promoter was always the
      strongest, generally by at least one order of magnitude. A comparison of the
      relative levels of expression seen between different cell types on transfection
      and infection suggest that not all CNS-derived cells are infected equally
      efficiently by rAAVs. High level of expression were seen within 24 h of transgene
      delivery by either transfection or infection, dropping dramatically within days.
      All cell types and promoters showed the same decline, suggesting that transient
      expression by rep-rAAVs may be efficient, but stable expression as detected in
      this system is a low frequency event. In vivo studies using the CMV promoter also
      suggest that although rep-rAAVs are able to infect efficiently CNS cells and
      produce high levels of gene expression shortly after transduction, the majority
      of such infections do not lead to stable high-level expression of transgenes.

PMID- 9156806
TI  - Adenovirus-mediated generation of cAMP-stimulated Cl- transport in cystic
      fibrosis airway epithelia in vitro: effect of promoter and administration method.
AB  - Cystic fibrosis (CF) is a common autosomal recesses disease in which loss of CFTR
      Cl- channel function of defective cAMP-stimulated Cl- transport transfer across
      airway epithelia. Recombinant adenoviruses have shown progress as vectors with
      which to transfer CFTR cDNA to CF airway epithelia. Here we investigated
      variables involved in adenovirus-mediated transfer of CFTR by measuring cAMP-
      stimulated Cl- transport in CF airway epithelia grown as monolayers on permeable
      filter supports. When we compared the effects of different promoters, we found
      that persistent correction of Cl- transport was obtained when the vector
      contained the E1a promoter, or to a lesser extent the PGK promoter. Vector
      containing the CMV promoter produced a greater initial cAMP-stimulated Cl-
      current, but the duration of correction was shorter and the infection procedure
      itself increased CFTR expression, suggesting that high input doses of virus
      stimulate expression. We compared the level of expression, measured with a beta
      galactosidase reporter of CFTR mRNA, with CFTR-mediated Cl- transport. Even low
      levels of expression generated significant Cl- current and marked increases in
      expression produced only modest increments in Cl- current. Correction of the CF
      Cl- transport defect was also improved when the concentration of adenovirus
      vector was high and when the duration of contact with the epithelium was
      prolonged. These findings may help optimize the ability of adenovirus vectors
      encoding CFTR to correct the CF Cl- transport defect.

PMID- 9156807
TI  - A novel DNA-peptide complex for efficient gene transfer and expression in
      mammalian cells.
AB  - To develop a nonviral gene delivery system for treatment of diseases, our
      strategy is to construct DNA complexes with short synthetic peptides that mimic
      the functions of viral proteins. We have designed and synthesized two peptides
      which emulate viral functions - a DNA condensing agent, YKAK(8)WK, and an
      amphipathic, pH-dependent endosomal releasing agent, GLFEALLELLESLWELLLEA. The
      active gene delivery complex was constructed step-wise through a spontaneous self
      assembly process involving oppositely charged, electrostatic interactions. To
      assemble DNA-peptide complexes with different overall net charges, only the
      negative charges of DNA phosphate, the positive charges of the 10 epsilon-amino
      groups of YKAK(8)WK and the negative charges of the 5 gamma-carboxyl groups of
      GLFEALLELLESLWELLLEA were considered. In the first step, negatively charged DNA
      was rapidly-mixed with an excess of YKAK(8)WK to form positively charged DNA
      YKAK(8)WK complexes, which gave little gene transfer. In the second step and to
      form the active complex,the cationic DNA complex was rapidly mixed with
      spontaneously incorporated through electrostatic interactions. Transfection using
      these complexes of CMV-luc, YKAK(8)WK and GLFEALLELLESLWELLLEA gave high-levels
      of gene expression in a variety of cell lines. These simple DNA complexes, which
      contain only three molecularly defined components, have general utility for gene
      delivery and can replace viral vectors and cationic lipids for some applications
      in gene therapy.

PMID- 9156808
TI  - [Multidisciplinary perspectives on the topic of age and aging].

PMID- 9156809
TI  - [Typology of illness in aging--consequences for prevention concepts].
AB  - Conventional dichotomy or three-part classifications for disease and age are not
      very helpful for practical application. The article presents a typology of
      disease, which we developed further into four categories. It considers the
      relation between physiological processes of aging and pathological developments
      as well as the courses of disease in old age. Adequate prevention strategies can
      be derived. Category I (physiological changes in old age which are only possibly
      a disease) demonstrates the importance of the context in illness. Physiological
      processes of aging with a high plasticity can be influenced by prevention
      strategies. Category II (age-related disease with a long latency period)
      demonstrates the problem of early recognition and secondary prevention. The
      category III (disease with different physiological process in old age because of
      reduced homeostatic regulation and repair mechanism) is not receptive to
      preventative concepts, but only to tertiary prevention and rehabilitation. In the
      category IV (disease as a result of long term exposure, increasing with lifetime)
      population-based prevention strategies are sensible.

PMID- 9156810
TI  - [Living conditions and mortality in the elderly after surgical management of para
      articular hip fractures].
AB  - While hemiendoprothesis has been established in the treatment of hip fractures of
      aged people because of less operative trauma, better effectiveness and satisfying
      functionality, surgical management of trochanteric fractures is still in
      discussion. In our study, we found no severe difference of living conditions or
      mortality after operating elderly patients with proximal femoral fractures
      comparing Hemiprotheses versus Endernails versus Dynamic Hip Screws.

PMID- 9156811
TI  - [Molecular mechanisms of senescence in cell culture].
AB  - Clones of non-transformed human cells are mortal, that is, the cells divide only
      a limited number of times before they approach a state of proliferative
      senescence. This state has long been regarded as a cellular model of organismal
      aging or as aging in vitro because of its close relationship to the aging process
      of the donor of the cells. The underlying molecular mechanisms of this particular
      aging process have only been recently understood and are reviewed in the present
      paper. Cell division is accompanied by progressive telomere shortening, which is
      due both to properties of the replicative apparatus (the "end-replication
      problem") and to oxidative damage to telomere DNA under conventional cell culture
      conditions. If shortening of telomeres reaches a certain critical level, it is
      recognized as DNA damage by the cell's "guardian of the genome", the tumor
      suppressor p53. Stabilization of p53 activates the well characterized cell cycle
      checkpoint at the G1/S phase boundary and blocks the cell cycle irreversibly. Two
      recent results prove that telomere shortening is in fact the trigger of the
      checkpoint control in cellular senescence: First, acceleration of telomere
      shortening by increased oxidative stress results in accelerated proliferative
      senescence. Second, stabilization of telomere length, typically by activation of
      telomere, appears to be a necessary prerequisite for the immortalization of
      cells. Proliferative senescence, therefore, should be understood as an important
      means to counteract genetic instability and cancer.

PMID- 9156812
TI  - [Histopathologic studies in dementia--comparison with clinical findings].
AB  - This paper compares the clinical diagnosis of dementia with the result of the
      neuropathological brain examination in 23 patients. Aim of this investigation was
      a verification of the clinical diagnosis. The diagnosis was based on the clinical
      findings, the Mini Mental State Examination, DSM-III-R classification of
      dementia, the NINCDS-ADRDA-criteria, results of laboratory tests, EEG, CCT and
      sonography. A total of 70% of the clinical diagnosis corresponded to the
      neuropathological results. In 25% of these cases which clinically showed the
      characteristics of Alzheimer's disease histopathological findings delineated
      dementia of non-Alzheimer-type. These results underline the importance of
      additional histopathological investigations in the diagnosis of dementia.

PMID- 9156813
TI  - [Longevity as a developmental process: life history and individual perspectives].
AB  - Longevity research often portrays the image that single characteristics of the
      past life explain best why some people survive into the second century of their
      lives, and others not. This paper challenges this approach by arguing that
      longevity should be seen as a life-long development process that still continues
      in the present lives of the oldest old. Four specific themes are addressed:
      First, individual differences can increase or decrease with age, depending on the
      domain studied. Second, historical events have shaped the individual biography of
      the oldest old and still have a profound impact on the personality and mental
      health of this age group. Third, individual events such as the loss of family
      members and friends are powerful recent experiences that challenge the oldest old
      to adapt to these recent changes in their lives. Finally, the oldest old seem to
      have unique time perspectives, realizing that remaining life expectancy is short
      and that time itself may not be of much importance to their current lives.

PMID- 9156814
TI  - [Unmarried women of the war generation: an explorative study of their goals in
      life and personal satisfaction].
AB  - Older never-married women are often confronted with negative stereotypes which
      find expression in terms like "spinster" or "old maid". Their life-situation,
      however, has rarely been a subject of empirical studies. In a research project at
      the University of Munster, started in 1985, some psychological and social aspects
      of the life-situation of never-married employed women born between 1919 and 1933
      (in comparison to married women of the same age not employed) were studied by
      means of detailed interviews. Parts of the results concerning "life goals" and
      "life satisfaction" are described. The results relativize the negative
      stereotypes mentioned above. They indicate that in the retrospective view of
      their lives the never-married women had many life goals which they could not
      achieve, but that they do not regret this at present. They rate their life
      satisfaction as very high and actively pursue present goals and interests. There
      are only few differences between never-married and married women. The results are
      discussed with regard to cognitive theories of aging and to the specific
      historical background of the interviewees.

PMID- 9156815
TI  - [Depressive mood and cognitive impairment in results of old age nursing homes].
AB  - Depression and cognitive impairment associated with dementia are among the most
      common psychiatric disorders faced by the elderly population. Compared to the
      elderly population in general, the prevalence of both depressive and cognitive
      disorders is usually higher in nursing homes. However, a valid assessment and
      differentiation of depression and dementia in old people is rather difficult. In
      our study, we examined the extent and co-occurrence of depression and cognitive
      impairment in a sample of 380 nursing home residents using psychometric tests and
      clinical rating scales (Geriatric Depression Scale, Mini-Mental-State
      Examination, Global Deterioration Scale). At least 50% of the nursing home
      residents showed a significant degree of cognitive impairment and depression was
      found in about 48% of those residents, who could be diagnosed (n = 263). The
      results indicated that the extent of depression was independent of subjects' age,
      and gender, and nursing home residence duration, whereas the degree of cognitive
      impairment was correlated with subject's age. Depressive and cognitive disorders
      coexisted in 15%-24% of nursing home residents. The frequency of co-occurrence of
      depressive and cognitive disorders was influenced by assessment methods of
      cognitive impairment.

PMID- 9156816
TI  - [Residents of homes for the aged in Germany: characteristics of social structure
      and choice of nursing home].
AB  - In this paper some important aspects of institutionalization in old age are
      studied. Compared with old people living in private households, people living in
      residential care facilities show some sociostructural particularities which are
      hints at possible factors related to institutionalization. The following analyses
      of the factors related to institutionalization in old age result in a conformity
      of objective and subjective reasons: poor health, lack of social network and bad
      housing conditions in combination with needs for care are essential factors
      related to institutionalization. In addition, the question of denominational
      choice of the residential care facility and the question about migration in old
      age is examined more closely. With regard to the religious community it is
      amazing that, in spite of secularization, there are major interdenominational
      differences. A further analysis of regional mobility suggests some
      sociostructural differences: women and widowed persons for example do not move
      over far distances (from the private household to the residential care facility),
      compared to men and married persons.

PMID- 9156818
TI  - [Does acute graft rejection modify subsequent function of a transplanted liver?].
AB  - While in kidney, heart and pancreas transplantation the impairment of graft
      function associated with acute rejection is only partially reversible upon
      successful antirejection therapy, little is known about the effect of acute
      rejection on late graft function after liver transplantation. Our data however
      gives similar findings in regards to conventional and quantitative liver function
      tests in patients with or without acute rejection more than 12 months after liver
      transplantation. This may most likely be attributable to the unique regeneration
      potential of the adult human liver.

PMID- 9156817
TI  - [Preservation of kidney transplants with a modified UW solution--initial clinical
      results].
AB  - Although the University of Wisconsin (UW) has become the standard solution for
      the preservation of kidneys for transplantation, the importance of the colloid
      hydroxyethylstarch (HES), one of the key compounds of the UW solution, has been
      judged controversial. It has been shown in various experimental models that
      dextran-40 may successfully substitute for HES. Dextran-40 is not only cheaper
      but also has a variety of biological effects which may be beneficial during the
      graft reperfusion phase. The aim of this clinical study was to examine the
      efficiacy of dextran-40 based preservation solution (Dex-PS) for its use for
      human kidney graft preservation and to compare the transplantation results with
      kidneys preserved with UW solution. A total of 87 kidneys were preserved with Dex
      PS and matched with 87 kidneys preserved with UW solution. Both groups were
      comparable in terms of donor and recipients characteristics. Patient survival and
      graft survival after 1 year was 95% and 86% for the Dex-PS group and 94% and 90%
      for the UW group, respectively (p = n.s.). Primary non-function, delayed graft
      function, postoperative need for dialysis, and follow-up of serum creatinine were
      statistically comparable between these two groups. We conclude that dextran-40
      can safely replace HES in the UW solution for the purpose of human kidney
      preservation for transplantation. There were no statistically detectable
      differences in graft performance between the kidneys preserved with UW and those
      preserved with Dex-PS.

PMID- 9156819
TI  - [Function of pancreas transplants in increased metabolic stress].
AB  - Patients undergoing successful pancreas transplantation have normal glucose
      levels in the fasting and fed states and normal levels of hemoglobin A1c without
      use of exogenous inulin or any other medications for diabetes. In some of these
      patients, these measures have remained stable for more than 10 years.
      Additionally pancreas transplant recipients recover from short-term hypoglycemia
      produced by an intravenous pulse of insulin. However, metabolic success has been
      determined by relatively routine, unsophisticated tests such as oral and
      intravenous glucose tolerance tests or stimulation with intravenous arginine.
      These tests may not provide measures of the functional reserve of the pancreas,
      which is called on during periods of maximal stress. Consequently, we designed
      studies to ascertain beta and alpha cell performance in recipients of whole
      pancreas transplants and recipients of a segment of a living related donor. All
      recipients were recruited from the University of Minnesota Transplant Registry,
      Minneapolis, Minnesota. Successfully transplanted recipients were subjected to
      prolonged hyperglycemia to assess insulin secretory reserve using the method of
      glucose potentiation of arginine induced insulin secretion and to prolonged
      hypoglycemia to assess glucagon responsiveness and hepatic glucose production
      using the technique of the hyperinsulinemic hypoglycemic clamp. Our studies show
      that pancreas transplant recipients have markedly diminished insulin secretory
      reserve, a defect not evident with conventional tests of beta-cell function. No
      difference was found between the whole graft and segmental graft recipients.
      Pancreas transplantation restores the defective glucagon secretory response and
      enhances hepatic glucose production during prolonged hypoglycemia in subjects
      with type I diabetes. We conclude that pancreas transplantation does not
      completely restore beta-cell secretory reserve. This defect might be probably
      caused in part by cyclosporine and by the procedure involved in transplanting a
      cadaveric pancreas. Pancreas transplantation normalizes hypoglycemia-induced
      glucagon secretion and hepatic glucose production, thereby allowing for
      normalization of glucose recovery from hypoglycemia.

PMID- 9156820
TI  - [Islets of Langerhans allografts in the pig: initial results].
AB  - Islet of Langerhans transplantation represents a promising treatment of diabetes.
      Use of porcine islets for xenotransplantation could offer a solution to shortage
      of organ donors. However, isolation of pig islets remains a real challenge
      because of their marked fragility. Using a modified automated method for islet
      isolation, we performed 10 intraportal islet allografts in pigs. Surgically
      pancreatectomized pigs were transplanted with purified islet preparations pooled
      from pancreases of 3 donors (slaughter-house pigs, age 5-8 months). Six
      recipients were not immunosuppressed and four received an immunosuppressive
      treatment of Cyclosporine and Azathioprine. In the first group (non
      immunosuppressed recipients), insulin secretion was observed for a mean of 4.8
      days after transplantation. In the second group (with immunosuppressive
      treatment) the recipients sustained an insulin secretion for 6-9 days. However,
      in both groups liver biopsies showed signs of acute rejection and destruction of
      the transplanted islets. Pig islet allotransplantation, using as recipients
      surgically pancreatectomized pigs, can be considered as a suitable model to
      assess the functional results of mass islet isolation. We were able to reverse
      diabetes transitory in a large animal, by transplantation of purified pig islet
      preparations. However, even when an immunosuppressive treatment was administered
      to the recipients, rejection seemed to represent an important factor in the
      functional outcome of the islet grafts.

PMID- 9156821
TI  - [Functional and morphological results of transplantation of vascularized knee
      joints in a dog model--a preliminary report].
AB  - Functional and morphological results of transplantation (n = 3) and replantation
      (n = 4) of vascularised total knee joints were compared in a canine model. Follow
      up time was 6 months. All vascular anastomoses remained patent and all
      osteotomies healed. Replanted animals displayed normal static weight bearing in
      contrast to the transplant recipients, which showed reduced weight bearing after
      6 months compared to preoperative values. Mild to moderate signs of chronic
      allograft rejection were detected in all transplanted animals. Functional results
      were correlated with morphological outcome demonstrating the relevance of
      adequate control of rejection.

PMID- 9156822
TI  - [Cryopreservation and bone transplantation].
AB  - Massive bone allografts allow us to treat easily large osseous defects. This
      study reports our experience with 90 massive allografts of whom 50 had more than
      2 years follow-up. The reconstruction was in half of cases the femur, in ten
      patients one or more vertebra, hemipelvis in five, humerus in four and tibia in
      three cases. The main indication was tumor surgery: 30 malignant, 6 benigns, but
      also for the treatment of massive bone loss in ten prothesis replacement and in 4
      miscellaneous pathology (malformation, infection ...). The massive allografts
      allow us more anatomic reconstructions and particularly in young patients we can
      observe some rehabitation of the graft by host cells. The complication rate is
      quite high mainly mechanical (10 fractures) in the first two years following
      surgery, but also 2 sepsis and 2 sciatic palsy. Simultaneously an experimental
      and morphological study of cartilaginous fragments was undertaken: at first, we
      define the best method of fixation and examination of human articular
      cartilaginous fragments by electronic microscopy. This method was then applied to
      cartilaginous fragments liable to various cryoprotective solutions, stocked for
      various periods at different temperature and subjects to programmed
      cryocongelation. So we are able to define the best conditions of cryoconservation
      of human adult articular cartilage fragments and we can observe that 70-80% of
      cells maintain normal morphological structure suggesting a perfect cellular
      viability.

PMID- 9156823
TI  - [Mechanism of rejection of islet of Langerhans xenografts].
AB  - For immediately vascularised xenografts, the presence of preformed antibodies
      associated with the activation of the complement induces a hyperacute humoral
      rejection in discordant combinations. For neovascularised xenografts, such as the
      islets of Langerhans, the absence of an initial vascularisation prevents the
      acute humoral rejection and there is some evidence to suggest that the rejection
      is cell mediated. To analyse the influence of species response to cellular
      transplantation, we compared the functional outcome and the immunohistochemical
      analysis of concordant and discordant xenotransplated islets with
      allotransplanted islets of Langerhans. In the concordant xenotransplantation
      experiment, rat (Sprague Dawley) purified islets (N = 600) were transplanted
      under the kidney capsule of streptozotocin diabetic mice. In the discordant
      experiment, purified human islets (N = 1000), in the allotransplantation model
      Balb mouse islets (N = 600) were transplanted under the kidney capsule of C57BL/6
      mice. Daily blood glucose levels were monitored until rejection occurred (blood
      glucose > 11 mMol/L) and kidney biopsies were taken every second day for
      immunohistological examination. In allotransplanted mice, rejection occurred
      after a mean of 15 +/- 4 days, in concordant xenotransplanted mice after a mean
      of 10 +/- 3 days and in the discordant xenotransplanted mice after a mean of 8 +/
      1 days. The immunohistological analysis showed in both xenotransplantation
      models a deposit of IgM and C3 surrounding the grafted cells, starting at day 1
      and persisting until rejection, associated with the presence of Mac-1 positive
      cells. The intensity of the humoral response was moderate to important in the
      concordant group, but very strong and unchanged until rejection in the
      disconcordant group. An invasion with CD4+ and CD8+ cells started between day 4
      and 6 in both groups, progressively increasing until rejection. In the
      allotransplantation model, no humoral response was detectable and the cellular
      response started between day 10 and 12 after transplantation. We conclude, that a
      cellular response is involved in the rejection process of both concordant and
      discordant xenotransplanted islets of Langerhans. Compared to an
      allotransplantation model, the humoral response does not destroy the function of
      transplanted islets, but could trigger or accelerate the cell-mediated response.

PMID- 9156824
TI  - Scleral fixation of posterior chamber intraocular lenses in children.
AB  - BACKGROUND AND OBJECTIVE: Children with monocular aphakia who become contact lens
      intolerant require an intraocular lens (IOL) for visual rehabilitation. When
      there is inadequate support from the posterior lens capsule, use of an anterior
      chamber IOL or a sclerally fixated posterior chamber IOL may be considered. The
      authors report their experience with scleral fixation of posterior chamber IOLs
      in children. PATIENTS AND METHODS: Seven posterior chamber IOLs were sutured in
      the ciliary sulcus of children who could not wear contact lenses. In each eye,
      the lens capsule remnants were inadequate to provide sufficient support for the
      haptics of a posterior chamber lens. RESULTS: Six of seven patients had improved
      visual acuity, with an average improvement of 4 lines. Complications related to
      scleral fixation included exposure of the scleral fixation suture in one eye,
      lens decentration in one eye, and lens tilt in one eye. Follow-up ranged from 3
      to 38 months, averaging 26 months. CONCLUSION: Implantation of a posterior
      chamber sclerally fixated IOL offers an alternative to placement of an anterior
      chamber lens in children who cannot wear contact lenses and who lack capsular
      support. Continued follow-up of these patients will help determine the long-term
      safety of this technique.

PMID- 9156825
TI  - Vitreomacular traction syndrome confused with pseudophakic cystoid macular edema.
AB  - Vitreomacular traction syndrome causes visual loss as a consequence of persistent
      traction on the fovea from an attached posterior hyaloid. The diagnosis can be
      challenging because the attachment may be subtle. Cystoid macular edema secondary
      to cataract extraction is well known and can occur in the absence of any surgical
      complication. Herein, a patient is described who had vitreomacular traction
      syndrome diagnosed after uneventful cataract surgery. Pars plana vitrectomy with
      detachment of the posterior hyaloid restored vision to an acceptable level.
      Careful examination and clinical suspicion are important because recognition and
      surgical intervention will benefit the majority of these patients.

PMID- 9156826
TI  - Pupillary block glaucoma due to residual perfluoro-decalin.
AB  - Perfluorocarbon liquids are used in vitreoretinal surgery and should be removed
      by the end of surgery. Removal is not always achieved and a few cases of
      complications resulting from perfluorocarbon liquid residues have been reported.
      The authors report a unique case of pupillary block glaucoma resulting from
      perfluoro-decalin residue in the anterior chamber that blocked a surgical
      coloboma of the iris at the 6-o'clock position. The perfluoro-decalin residue
      dissolved spontaneously with antiglaucoma treatment and no surgical intervention
      was needed. When perfluorocarbon liquids are used during pars plana vitrectomy,
      the possibility of silicone-induced pupillary block in the presence of an
      inferior iris coloboma should not be overlooked.

PMID- 9156827
TI  - Bilateral fascia lata patch grafts in a patient with progressive scleromalacia
      perforans.
AB  - This study was performed to evaluate the use of autogenous fascia lata patch
      grafts with systemic immunosuppression in the treatment of progressive bilateral
      scleromalacia perforans. Autogenous fascia lata was compared with donor bank
      sclera and was demonstrated to be more suitable for this condition.

PMID- 9156828
TI  - An alternative method of closed silicone intubation of the lacrimal system.
AB  - An alternative method of closed lacrimal intubation is described, the basis of
      which is to place the end of a piece of silicone tubing over the end of a small
      diameter metal introducer, stretch the silicone tubing back along the introducer,
      and then pass the introducer together with the tubing through the lacrimal system
      into the nasal cavity. The tubing is visualized in the inferior meatus, from
      where it is retrieved, and then the introducer is withdrawn. The other end of the
      tubing is passed in a similar fashion. The technique is easily mastered,
      inexpensive, and less traumatic than other described techniques.

PMID- 9156829
TI  - Prevention of accidental intraocular injection following inadvertent needle
      perforation of the eyeball.
AB  - To prevent accidental intraocular injection after inadvertent single needle
      perforation of the eyeball, the authors recommend moving the needle and watching
      for corresponding movement of the globe following peribulbar or retrobulbar
      placement of the needle and prior to injecting. The authors have found this
      technique to be safe and reliable, with negligible morbidity.

PMID- 9156830
TI  - Canadian veterinary organizations--time to reorganize?

PMID- 9156831
TI  - The history of esophageal surgery: pediatric aspects.
AB  - An attempt is made to explore those aspects of the history of esophageal surgery
      relevant to pediatric practice. In some areas, the history is entirely focused on
      conditions of particular pediatric significance; esophageal atresia is a classic
      example of this group. In other areas there is considerable overlap, which varies
      in extent, with the history of esophageal surgery in adult. Conditions to be
      considered in this group include gastroesophageal reflux and peptic and corrosive
      esophagitis. Finally, there is a group that for all practical purposes is related
      to patients in the adult age group, exemplified by carcinoma of the esophagus,
      but some aspects of the history of surgery for esophageal cancer are relevant to
      pediatric practice, particularly in the area of reconstruction of the alimentary
      tract and esophageal replacement. Before the consideration of each of these
      groups, comments are directed toward the "early days"" or the beginnings.

PMID- 9156832
TI  - Specific and nonspecific lymphadenitis in childhood: etiology, diagnosis, and
      therapy.
AB  - Over a period of 4 years, 39 children with lymphadenitis were treated surgically;
      in 31 cases cervical lymph nodes were the main location. In 9 cases the
      lymphadenitis was caused by mycobacterial infection. Staphylococcus aureus was
      the most frequent causative organism of unspecific lymphadenitis (11 cases). The
      therapy of choice appears to be surgical treatment and medical care after
      operation. Especially in mycobacterial lymphadenitis, complete surgical excision
      of the lymph node is decisive for definitive healing. There was only 1 case of
      therapy-resistant, relapsing cervical lymphadenitis that needed a second
      operation. Causative organisms in this case were Mycobacterium avium and
      Mycobacterium intracellulare. All other patients showed an uneventful
      postoperative clinical course. We believe that a consequent diagnostic process
      and cooperation between the pediatric surgeon and pediatrician are necessary for
      effective therapy.

PMID- 9156833
TI  - Thymectomy in black children with juvenile myasthenia gravis.
AB  - Fifteen black children with juvenile myasthenia gravis presented to our
      institution over a 10-year period at ages ranging from 18 months to 7 years, 4
      males and 11 females. Twelve presented with progressive, generalised weakness and
      3 had bulbar manifestations. Ocular signs were absent in 2 patients. All 15
      patients were placed on pyridostigmine bromide (Mestinon) and 1 also required
      steroids and plasmapheresis. Medical therapy only was instituted in 5 patients,
      of whom 2 came to surgery, 2 died, and 1 was lost to follow-up. Thymectomy was
      performed in 12 children (including the 2 with failed medical therapy) via a
      median sternotomy with no mortality or morbidity related to the operation. The
      timing of surgery was less than 3 months in 75% of the children. Thymic
      hyperplasia was noted in 10 glands and 2 were reported as normal. Of the children
      in the operative group, 83% are on minimal medication or in total remission.
      Better results were noted in young patients with early thymectomy and diseased
      glands.

PMID- 9156834
TI  - Thoracoscopic surgery of the oesophagus in rats: a training concept for the
      treatment of tracheo-oesophageal malformations in preterm infants.
AB  - In extremely preterm babies with type Vogt III b oesophageal atresia, the primary
      operative management can be restricted to a gastrostomy and ligation of the
      fistula. Some of these patients, however, may not even tolerate a thoracotomy or
      placement on the operating table. We developed a minimally invasive procedure to
      prepare and ligate the oesophagus thoracoscopically and perform laparoscopic
      gastrostomy in a rat model. In 15 operations we observed only one complication.
      This study implies that after adequate practice, thoracoscopic dissection of the
      oesophagus with ligation of a tracheo-oesophageal fistula could be performed even
      in every small infants.

PMID- 9156835
TI  - Bronchial foreign body: should bronchoscopy be performed in all patients with a
      choking crisis?
AB  - The aspiration of a bronchial foreign body (FB) remains a common pediatric
      problem with serious and sometimes fatal sequelae. The diagnosis is often delayed
      or overlooked. With the aim of determining a reliable clinical and/or radiologic
      finding to indicate the requirement for bronchoscopy, 100 patients admitted to
      our hospital because of FB aspiration who underwent rigid bronchoscopy were
      retrospectively studied. The clinical and radiologic data were compared with the
      bronchoscopy findings, which revealed that the history of a choking crisis was
      the clinical parameter that showed the highest sensitivity (97%) with high
      specificity (63%), and that other symptoms and radiology, even those with high
      sensitivity (88% and 85%, respectively), had low specificity (9%). We conclude
      that bronchoscopy should be performed in all patients with a history of a choking
      crisis even if they have normal radiologic findings and few symptoms.

PMID- 9156836
TI  - Morphometrics of normal and hypoplastic lungs in preterm lambs with gas and
      partial liquid ventilation.
AB  - To test the hypothesis that perfluorochemical (PFC) instillation may reduce the
      pulmonary trauma commonly associated with conventional gas ventilation, we
      studied 12 lambs with normal lungs and 10 with pulmonary hypoplasia secondary to
      congenital diaphragmatic hernia (CDH). We used mechanical ventilation for up to
      3.5 h, with and without tracheal instillation of LiquiVent PFC liquid. At the end
      of experimentation lungs were fixed for morphometrical analysis of their
      components and pulmonary trauma was evaluated by measurement of the perivascular
      compression index (PCI = % perivascular emphysema/% vessels). In normal lungs
      good gas exchange and respiratory mechanics were obtained with all modes of
      ventilation, with no statistical difference in the index of pulmonary trauma with
      or without instillation of LiquiVent (P >0.05). In the hypoplastic lungs,
      tracheal instillation of PFC liquid after 30 min of conventional gas ventilation
      significantly improved PaCO2 (from 107+/-8 to 55+/-6 mmHg, P <0.05), pH (from
      7.00+/-0.03 to 7.29+/-0. 04, P <0.05), compliance (from 0.08+/-0.01 to 0.25+/
      0.03 ml/cmH2O . kg, P <0.05), and ventilatory index (from 1,445+/-148 to 794+/
      139, P <0.05). Survival was 6/6 animals with PFC ventilation compared to 1/4 with
      conventional gas ventilation with no more pulmonary trauma (mean PCI 12.6+/-1.8
      vs. 11.4+/-4.0%, P >0.05) for a longer mean ventilatory period in the PFC group.
      We conclude that the PFC liquid technique of ventilation can improve respiratory
      physiology when conventional gas ventilation alone is proving inefficient. There
      was no significant difference in pulmonary trauma at morphometrics between gas
      and partial liquid ventilation.

PMID- 9156837
TI  - Congenital adenomatoid disease of the lung: prenatal diagnosis and perinatal
      management.
AB  - Prenatal ultrasonographic (US) detection of congenital adenomatoid malformation
      (CAM) was made in 18 fetuses at 17 - 36 weeks' gestation and managed in our
      institution during a 10-year period (1985-1994). The lesion was left-sided in 13
      cases, right-sided in 4, and bilateral in 1. According to Stocker's
      classification, 12 cases were type I, 4 type II, and 2 type III. The prenatal
      course was followed with serial US examinations in 13 cases; the size of the
      lesion was stable in 8 and decreased in 5. Mediastinal shift was usually
      observed, and amniotic fluid volume was increased in 4 cases. One fetus was
      aborted. Six infants presented with respiratory distress syndrome and required
      neonatal surgery; delayed surgery was performed in 9 cases. Spontaneous
      regression of the lesion was observed on follow-up in 2 cases. Surgery consisted
      in lobectomy in 8 cases and segmentectomy in 6. The presence of fetal hydrops,
      type III lesions, and bilateral lung involvement are prenatal factors known to be
      associated with a poor prognosis. However, this series and a review of the
      literature suggest that caution should be observed with regard to the initial
      impression when counseling the parents regarding prognosis.

PMID- 9156838
TI  - Laparoscopically assisted percutaneous endoscopic gastrostomy.
AB  - The percutaneous endoscopic approach is an established method for fashioning a
      gastrostomy. However, the technique is not without complications. Visualising the
      peritoneal cavity via a small laparoscope may provide additional safety to
      percutaneous endoscopic gastrostomy.

PMID- 9156839
TI  - Laparoscopic diagnosis of blunt abdominal trauma in children.
AB  - This study evaluates the safety and role of laparoscopy in the diagnosis of blunt
      abdominal trauma in children. Laparoscopy was performed in five patients aged 3
      to 13 years because of persistent abdominal pain after blunt trauma. A laparotomy
      was not indicated from the physical examination, laboratory data, or radiologic
      findings. With the patient under general anesthesia, a 10-mm trocar was inserted
      through the umbilical fossa and the intra-abdominal organs were observed for 10 -
      60 min under an insufflation pressure of 10 - 12 mmHg. The patients remained
      hemodynamically stable without pneumothorax development. Three patients underwent
      laparatomies: one, who had blood in the omental sac, had a duodenal injury with
      hemorrhagic necrosis and underwent a resection; one with ascites and high amylase
      levels had an injury of the main pancreatic duct and underwent resection of the
      pancreatic tail; and one who had fresh blood in the upper abdomen and Douglas'
      pouch had a splenic hemorrhage and underwent hemostasis. The other two had serous
      or serosanguinous ascites and recovered without surgery. In patient 1, the same
      amount of information might have been obtained from a barium study. In patient 2,
      the pancreatic transection might have been diagnosed from ascites shown on serial
      computed tomograms. Patient 3 might also have been treated successfully non
      surgically. It hus appears that laparoscopy may be a safe diagnostic method for
      blunt abdominal trauma in children, however, this small series has yielded
      insufficient information to assess its usefulness in making the diagnosis and the
      decision for laparotomy. Further studies are required to ascertain whether it
      will make any significant difference in the form of management.

PMID- 9156840
TI  - Laparotomy or drain for perforated necrotizing enterocolitis: who gets what and
      why?
AB  - Between 1974 and 1988, 86 newborns with perforated necrotizing enterocolitis
      (NEC) were treated by either laparotomy (usually involving a bowel resection and
      a temporary stoma) or a peritoneal drain under local anesthesia. The survival of
      babies in the laparotomy group was 57% versus 59% in the drained group. However,
      for neonates less than 1,000 g survival in the drained group was 69% compared to
      22% for the laparotomy group (P <.01). As the weight of the babies increased over
      1,000 g, the survival in the laparotomy group increased to 67%. There was no
      significant increase in survival in infants over 1,500 g. The highest neonatal
      mortality risk is generally found among babies weighing less than 1,000 g at
      birth with a gestational age of less than 30 weeks. This risk increases even more
      when perforated NEC is added to the prematurity. With the use of peritoneal
      drainage, survival in this group can approach that of larger neonates.

PMID- 9156841
TI  - T-tubes in the management of meconium ileus.
AB  - Fifteen cases of meconium ileus (MI) were treated between 1986 and 1995; 7
      responded to conservative treatment. Eight were operated upon, and comprise the
      study group. Six of the operated babies had no complications; 1 had meconium
      peritonitis with a pseudocyst and small-bowel atresia, and 1 had a volvulus of a
      small-bowel segment with necrosis. In all 8 cases a T-tube (TT) was left via an
      enterotomy; in the complicated cases the enterotomy was pre-anastomotic. The
      obstruction was relieved in all the babies, without any stoma or bowel resection
      in the uncomplicated cases. Two complications occurred: 1 patient died of
      respiratory failure 1 month following surgery and another required a relaparotomy
      for lysis of adhesions. We conclude that TT ileostomy is an effective and safe
      procedure for uncomplicated cases of MI that do not respond to conservative
      therapy, as well as for complicated cases that need an anastomosis.

PMID- 9156842
TI  - Colorectal resection and anal anastomosis with an intraluminal stapler in
      Hirschsprung's disease.
AB  - Twenty patients aged 5 months - 4 years (mean 14 months) with Hirschsprung's
      disease were operated upon. In all cases a pull-through resection and stapled
      circular coloanal anastomosis was performed, in 11 with a single-stapling
      technique and in 9 with double-stapling. Isopaque rectography 4 - 10 days
      postoperatively showed an intact anastomosis in all 20 patients, i. e., there
      were no clinical or subclinical leaks. On palpation 4 - 6 weeks postoperatively,
      there were signs of stenosis in 4 patients. However, no. 9 - 11 Hegar dilators
      passed easily and there was no residual stenosis at follow-up 3 months after
      surgery. The technique can be recommended in children over 6 months of age.

PMID- 9156843
TI  - Surgical tactics in the treatment of malignant renal tumors in childhood.
AB  - The authors report the treatment results of 89 children with renal tumors
      (excluding carcinoma) seen from 1988 to 1992, 71 (79.8%) with favorable-histology
      Wilms' tumor (survival 86%) and 18 (20.2%) with unfavorable histology, including
      anaplastic nephroblastoma, clear-cell sarcoma, and rhabdoid tumor (survival 61%).
      Preoperative chemotherapy (ChT) was given to 46 patients (survival 84%); none was
      given to 43 with either tumors in the 1st year of life, massive hematuria, or
      tumor growth during ChT (survival 78%). There were 3 tumor ruptures in the latter
      group compared to 1 in the former group.

PMID- 9156844
TI  - Occult spinal dysraphism: neurogenic voiding dysfunction and long-term urologic
      follow-up.
AB  - From 1976 to 1994, we followed 55 children with occult spinal dysraphism (OSD).
      The average age at diagnosis was 4.5 years (range: 24 days - 21 years). In 13
      cases the OSD was associated with anorectal anomalies. Urologic symptoms were
      present at diagnosis in 24 children (43%), but urinary incontinence affected all
      patients in the evolution of the OSD. At diagnosis, all children underwent
      complete neurourologic and urodynamic evaluation. Nine required early
      neurosurgical correction, before 3 years of age. During follow-up, intermittent
      clean catheterization was started in all patients. Vesicoureteral reflux was
      present or developed in 17 patients: 15 underwent endoscopic procedures and 2
      required bladder augmentation because of upper-tract and renal-function
      deterioration. Endoscopic treatment for urinary incontinence was performed in 3
      children. At long-term follow-up (6 to 18 years), socially acceptable continence
      was achieved in 78% of the children; renal failure occurred in 8. The long-term
      results were analyzed in order to compare the evolution of urinary continence and
      renal function in children with OSD with or without neurosurgery.

PMID- 9156845
TI  - A transvesical approach to mullerian duct remnants.
AB  - Surgical extirpation is the treatment of choice for symptomatic mullerian duct
      remnants (prostatic utricle, PU), and several surgical approaches have been
      described for the treatment of this pathology. A group of 11 patients with
      symptomatic PU were observed and treated. Associated anomalies included proximal
      or penoscrotal hypospadias in all patients and cryptorchidism in 9 (81.8%). In
      all cases the PU needed surgical correction, as the patients had recurring
      symptomatology. Surgery was carried out transvesically in 10 (91%) cases and in 1
      a perineal approach was used. There were no surgical complications, and at follow
      up all patients showed complete resolution of the symptoms. We believe the
      transvesical approach, compared to other techniques, is more advantageous in the
      treatment of this pathology, as it permits excellent exposure, ease of surgery,
      good reconstruction, and good functional results with no sequelae.

PMID- 9156846
TI  - Is the ascending testis actually 'stationary'? Normal elongation of the spermatic
      cord is prevented by a fibrous remnant of the processus vaginalis.
AB  - The processus vaginalis (PV) forms as a peritoneal diverticulum within the
      gubernaculum testis to allow the testis to exit from the abdominal cavity.
      Failure of its closure leads to inguinal hernias and hydroceles. Ascending
      testis, which is likely to be an acquired form of undescended testis, may also be
      part of the spectrum of failure of regression of the PV. At orchidopexy for
      cryptorchidism in older boys with a history of a scrotal testis in infancy, we
      find that the PV persists as a fibrous string, preventing normal elongation of
      the vas deferens and gonadal vessels with increasing size of the boy. We propose
      that the ascending testis is actually 'stationary', and is caused by persistence
      of a fibrous remnant of the PV. Seen in this light, ascending testes are directly
      related to inguinal hernias.

PMID- 9156847
TI  - Gross morphologic variations and histologic changes in cryptorchid testes.
AB  - Cryptorchid testes are frequently accompanied by gross morphologic changes with
      regard to the size and shape of the testis, various degrees of detachment between
      the epididymis and testis, elongation of the caudal epididymis and vas deferens,
      as well as histologic changes. This study examined the gross and microscopic
      testicular, epididymal, and vas changes in relation to various parameters in 824
      patients operated upon in our clinic during the last decade. The major findings
      were the following: (1) most patients (78.8%) were older than 4 years, and many
      older than 8 years (39.8%); (2) the frequency of abdominal undescended testes
      decreased with increasing age (P <0.1), while the frequency of suprascrotal
      testes increased with increasing age (P <0.001); (3) most of the undescended
      testes in a suprascrotal position were normal or had mild atrophy (78.7%), while
      those in intracanalicular, internal ring, and abdominal positions frequently
      presented moderate or severe atrophy (71,38%; (P <0.0001); and (4) most
      suprascrotal testes were either normal or had mild extension and looping of the
      epididymis (63.8%), while most of the intracanalicular, internal ring, and
      abdominal testes showed moderate or profound epididymal anomalies (63.4%; P
      <0.0001). We conclude that even though the necessity for early surgical
      correction of cryptorchidism is well established, these patients at least in our
      region, still tend to come very late to surgery, with consequent increased risks
      of infertility and malignant transformation.

PMID- 9156848
TI  - Orchidopexy: the relative importance of each step of mobilisation.
AB  - Measurements were recorded during 313 orchidopexies to assess the relative
      importance of each step of the procedure. Division of the sac or processus
      accounts for 60% of the increased length of the cord (1.453 cm), whilst the
      remaining 40% (1.048 cm) of the total net gain (2.501 cm) is due to dissection
      within the internal inguinal ring. Division of the lateral bands is an essential
      step to achieve a successful orchidopexy.

PMID- 9156849
TI  - Undescended testes: early versus late maldescent.
AB  - A review of 468 orchidopexies was undertaken to ascertain the importance of a
      complete hernial sac extending to or beyond the testis. A hernial sac was present
      in 84% (171/202) of testes in patients under 5 years of age, in contrast to 23%
      (61/266) in patients over 5 years. It seems reasonable to presume that the
      failure of the hernial sac to close is secondary to failure of normal descent,
      which in turn is due to antenatal factors and may be classified as "early
      maldescent". In the older age group maldescent is due to failure of the last
      stage of descent, which should occur in the 5- to 10-year prepubertal age period
      ("late maldescent", or the "ascending" testis). The cause of late maldescent is
      not due to a short processus, as this increases in length with age (approximately
      0.5 cm/year), unless the persistence of the processus itself is the cause. A
      classification of early or late maldescent is suggested.

PMID- 9156850
TI  - Labial skin-flap vaginoplasty using tissue expanders.
AB  - In severe vaginal malformations, when the distance between the upper vaginal
      pouch and perineum is too long (6 cm or more), reconstruction of the vagina can
      be performed by colonic interposition or by long cutaneous flaps obtained by the
      tissue expansion technique. Two female adolescents were treated using expanded
      labial skin flaps. Dissection and anastomosis between the vaginal remnant and
      cutaneous tube was performed by the transtrigonal approach. Results were
      satisfactory at 2.5-year follow-up. In our opinion, expanded labial skin-flap
      vaginoplasty has three main advantages: (1) it permits the construction of a
      large, soft, well-vascularized neovagina using non-hair-bearing labial skin; (2)
      it obviates postoperative dilations and prevents delayed strictures; and (3) a
      transtrigonal approach permits an easy vaginal dissection and a careful, tension
      free anastomosis.

PMID- 9156851
TI  - Towards reducing the trauma of direct intracompartmental pressure measurement for
      children: an in vitro assessment of small-diameter needles.
AB  - Direct intracompartmental pressure (ICP) measurement in children is an important
      investigation, the use of which may be inhibited by the invasive nature of the
      procedure and the large 18-gauge (G) needles that have hitherto been recommended.
      These large needles contribute to patient, parental, and physician anxiety. This
      study compares ICP measurements using needles of different lengths and port
      configuration, ranging from 18 to 25 G, against the "gold standard" 18 G, long,
      double-ported needle. All except the 18 G long, single-ported needle had limits
      of agreement within 3 mm Hg of the gold-standard needle. The results indicate
      that needle manometry can confidently be performed using small needles, and that
      the addition of a side-port is unnecessary in needles of small volume.

PMID- 9156852
TI  - Critical appraisal of surgical venous access in children.
AB  - Central venous catheters (CVC) have become an important adjunct to the overall
      management of paediatric patients, but their use is associated with frequent
      complications resulting in premature removal. This report evaluates the insertion
      techniques and complications of 295 consecutive surgically inserted CVC from 1987
      to 1991 in a paediatric hospital. Fully implanted catheters had significantly
      less incidence of catheter-related problems necessitating removal (infection,
      dislodgment, leaking, blockage, or migration - 31%) compared to exteriorised
      catheters (58%). One-third of catheters were removed because of infection, one
      third as they were no longer needed, and the remaining for multiple reasons.
      Infected (110+/-18 days), dislodged (18+/-4 days), or migrated (44+/-6 days)
      catheters were removed significantly earlier than those removed because they were
      no longer needed (195+/-24 days). Catheters became dislodged more frequently in
      the younger patients. Catheters with the tip in the subclavian vein (29%)
      migrated more frequently than those in the right atrium. There was a
      significantly increased incidence of infection in catheters inserted into the
      saphenous vein (43%) compared to those in the internal jugular vein (11%). Some
      episodes of catheter infection were managed with antibiotics, with short-term
      resolution of symptoms and signs. However, all 71 infected catheters ultimately
      required removal for further sepsis. Fully implanted catheters had 1.1 episodes
      of catheter-related sepsis per 1,000 catheter days compared to 3.7 for
      exteriorised catheters. The position of the catheter tip, vein used for
      insertion, training of young surgeons, and location of the subcutaneous tunnel
      need particular attention in order to reduce catheter complications.

PMID- 9156853
TI  - Brain heterotopia: choristoma of the back.
AB  - Heterotopic brain tissue, except in the head and neck region, is exceedingly
      rare. Mature neural tissue unexpectedly found in the subcutaneous tissues of the
      back of a toddler lacked an attachment to the central nervous system (CNS), and
      appeared to be unorganized glial tissue on pathologic evaluation. Appropriate
      clinical management of such lesions includes a suspicion of subcutaneous lesions
      near the CNS and evaluation to eliminate the presence of communication with the
      CNS, followed by surgical excision.

PMID- 9156854
TI  - A new variant of esophageal atresia with tracheoesophageal fistula and duodenal
      atresia: a diagnostic dilemma.
AB  - A new variant of esophageal atresia (EA) with tracheoesophageal fistula (TEF)
      associated with duodenal atresia is reported. The TEF was between the lower pouch
      and the trachea, with a cystic dilatation in the midportion. The tracheal end of
      the fistula was obstructed by a membranous septum at both ends of a cystic
      dilatation, leading to a diagnosis of pure EA (gasless abdomen). After the lower
      pouch was opened beyond the cystic dilatation, 100 ml nonbilious fluid was
      obtained. A laparotomy revealed a type III atresia of the first part of the
      duodenum.

PMID- 9156855
TI  - Beta haemolytic streptococcal infection does not cause right diaphragmatic
      eventration.
AB  - Numerous case reports in the literature have suggested a causal link between beta
      haemolytic streptococcal infection and delayed-onset right-sided diaphragmatic
      hernia/eventration in the perinatal age group. We report a child with antenatally
      documented right diaphragmatic eventration 4 weeks before birth who subsequently
      developed a beta-haemolytic streptococcal infection in the neonatal period.

PMID- 9156856
TI  - Bezoar formation and malabsorption secondary to persistent dilatation and
      dysmotility of the duodenum after repair of proximal jejunal atresia.
AB  - Bezoar formation is a rare but well-recognised complication of previous gastric
      surgery and persimmon ingestion. We present a case of bezoar formation in the
      duodenum of a child with a grossly dilated, dysmotile duodenum following surgery
      for jejunal atresia. The presenting symptoms were vomiting, diarrhoea, and growth
      failure, with evidence of malabsorption secondary to bacterial overgrowth in the
      bezoar. Plication of the duodenum to reduce its size and improve its motility may
      reduce the likelihood of future bezoar formation.

PMID- 9156857
TI  - Malignant gastric teratoma: case report.
AB  - Gastric teratomas are rare and usually benign. A 4 month old boy presented with
      an abdominal mass and computed tomographic and ultrasound examination
      demonstrated a large multi-loculated tumour which was totally excised. The
      pathological diagnosis was of a malignant gastric teratoma and 12-month follow-up
      was uneventful.

PMID- 9156858
TI  - Pyloroduodenal duplication cyst: case report.
AB  - A 6-day-old female presented with vomiting and an abdominal mass. At laparotomy,
      a pyloroduodenal duplication cyst was enucleated from the pyloric region. Of the
      diagnostic studies performed, IV cholangiography with spiral computed tomography
      and an upper gastrointestinal barium study were useful in the preoperative
      differential diagnosis.

PMID- 9156859
TI  - Congenital intrahepatic portocaval shunt associated with trimethylaminuria.
AB  - A case of congenital portal-systemic shunting due to an intrahepatic connection
      diagnosed by ultrasound scanning and color Doppler in an 8-month-old girl is
      reported. She began to manifest trimethylaminuria 3 years later. At 7 years of
      age, she is asymptomatic without therapeutic measures except for diet. This is
      the seventh reported case and the third in a child to our knowledge.

PMID- 9156860
TI  - Cholelithiasis in early infancy.
AB  - This report describes three children, age range 7 weeks to 5 months, who
      presented with obstructive jaundice secondary to gallstones. Previous Escherichia
      coli septicaemia and frusemide therapy were predisposing risk factors in two of
      the patients. All three were successfully treated with cholecystectomy and
      exploration of the common bile duct.

PMID- 9156861
TI  - Rhabdomyosarcoma of the biliary tree.
AB  - Rhabdomyosarcoma (RMS) of the biliary tree is a rare tumor in children that has a
      very poor prognosis. Preoperatively, it is often mistaken for a choledochal cyst.
      We report a case of RMS of the biliary tree in a 4-year-old girl who presented
      with abdominal pain and obstructive jaundice. The RMS was diagnosed at
      laparotomy; excision was not possible due to its size and localization.
      Chemotherapy achieved complete regression of the tumor observed at second-look
      surgery. Preoperative chemotherapy can now avoid mutilating surgical procedures
      and improve survival.

PMID- 9156862
TI  - Haemorrhage from a duodenal ulcer in a neonate.
AB  - A 7-week-old boy born at 32 weeks' gestation developed massive upper
      gastrointestinal bleeding from a duodenal ulcer. The base of the ulcer had eroded
      into the hepatic artery. Haemorrhage was only controlled following operation.

PMID- 9156863
TI  - Fetiform teratoma arising from a tubular intestinal duplication. A probable cause
      of ruptured exomphalos.
AB  - A neonate who had a ruptured exomphalos with a fetiform teratoma arising from the
      end of a long intestinal tubular duplication and a short gut is presented. The
      management is discussed and the literature is reviewed.

PMID- 9156864
TI  - Myoepithelial hamartoma of the ileum causing intussusception in an infant.
AB  - Intussusception is a relatively common pediatric gastrointestinal emergency,
      although the etiology in most cases remains unknown. In a small number of cases
      the lead point is a tumor or tumor-like lesion of the small bowel. We report an
      unusual case of a myoepithelial hamartoma of the ileum causing an intussusception
      in a 4-month-old boy. This is the second such report in the literature.

PMID- 9156865
TI  - Combination of "patch, drain, and wait" and home total parenteral nutrition for
      midgut volvulus with massive ischemia/necrosis.
AB  - The successful use of a combination of "patch, drain, and wait" (PDW) and home
      total parenteral nutrition (TPN) in the management of a case of acute,
      catastrophic midgut volvulus in a 2-year-11-month-old boy with near-total
      ischemia/necrosis of his small intestine is reported. The PDW approach to the
      highly effective management of acute midgut ischemia/necrosis in infancy and
      childhood (necrotizing enterocolitis and midgut volvulus) involves maximum gut
      salvage by avoidance of resection, stoma formation, or both through the use of
      extensive peritoneal cavity drainage by Penrose drains, TPN, and broad-spectrum
      antibiotics. The extensive peritoneal drainage fosters capture of enteric
      fistulas with the formation of enterostomies at drain exit sites, while adhesions
      and ischemia/inflammation-induced hypervascular obliteration of the peritoneal
      cavity diminish the potential for peritonitis (no peritoneal cavity, no
      peritonitis) and facilitate impressive salvage of seemingly hopelessly lost
      ischemic/necrotic gut (a simulation of the in utero ischemic gut process leading
      to atresias and some varying, but generally mild, gut loss) while simultaneously
      contributing to the resorption of absolutely non-salvageable gut and the creation
      of a remarkably clean and adhesion-free peritoneal cavity resembling that of a
      newborn infant with midgut intestinal atresia.

PMID- 9156866
TI  - Lower gastrointestinal tract perforation in preterm infants treated with
      dexamethasone for bronchopulmonary dysplasia.
AB  - Two cases of ileal perforation in preterm infants treated with high-dose
      dexamethasone for bronchopulmonary dysplasia are described. Corticosteroid
      induced gastroduodenal haemorrhage or perforation has been well documented, but
      less known to most clinicians is that the lower gastrointestinal tract can also
      be involved. Unlike previous reported cases in which affected infants
      deteriorated rapidly and became moribund within hours of onset of symptoms,
      "silent" perforations detected on routine radiograph or escaping clinical
      recognition until at an advanced stage can be the initial presentation. The need
      for greater vigilance and a low threshold for abdominal investigations are
      emphasised in preterm infants treated with dexamethasone.

PMID- 9156867
TI  - Psoas abscess associated with renal pathology in children.
AB  - Pyogenic psoas abscess in children is most commonly a primary disease process
      associated with Staphylococcus aureus. We report three cases of secondary psoas
      abscess associated with underlying renal pathology.

PMID- 9156868
TI  - Wandering calcified ovary in children.
AB  - A case of a mobile, calcified, intrapelvic mass representing an autoamputated
      ovary in an asymptomatic girl is presented. There was no previous history of
      acute abdominal pain indicating possible torsion of the adnexa. The diagnosis
      should be suspected when radiological investigations show a freely mobile,
      calcified intraperitoneal mass incidentally in young females with absent adnexa.
      The diagnostic and therapeutic role of laparoscopy in this case is emphasised.

PMID- 9156869
TI  - Accessory scrotum with imperforate anus.
AB  - Accessory scrotum is the rarest anomaly of the scrotum; less than two dozen cases
      have been reported. A case of accessory scrotum with imperforate anus is
      reported.

PMID- 9156870
TI  - Transverse testicular ectopia: report of three cases.
AB  - Two patients who presented with a history of right inguinal hernia and a third
      with an impalpable left testis were found to have transverse testicular ectopia.
      Both testes were fixed in their own scrotum, through a modified Ombredanne
      operation in two patients and a subdartos pouch in one.

PMID- 9156871
TI  - Is BCG vaccine innocent?
AB  - Four patients admitted to the Hacettepe University Department of Pediatric
      Surgery between 1987 and 1995, two with Bacille Calmette-Guerin (BCG)
      lymphadenitis and two with multisystem postvaccination tuberculosis (MPT), are
      presented. The hospital records and records of the Ministery of Health
      Tuberculosis Control Department were evaluated to determine the complications of
      BCG vaccine. The most common complication was lymphadenitis with or without
      suppuration (0.3 per thousand - 3 per thousand). Surgical intervention was
      required in two BCG lymphadenitis cases and two cases of MPT. Involved lymph
      nodes were excised in two lymphadenitis cases. Colostomy and percutaneous
      nephrostomy was performed in the first case of MPT in addition to triple
      antituberculous drug therapy. Although BCG lymphadenitis is self limited,
      chronically discharging nodes and tumor-like lymphadenopathy masses need to be
      excised. On the other hand, MPT has a silent nature with resistance to
      antituberculous drug therapy. Surgical intervention may be required, directed to
      the involved systems.

PMID- 9156872
TI  - Congenital pyloric stenosis: a modified umbilical incision for pyloromyotomy.
AB  - Thirty-two patients underwent a pyloromyotomy via an umbilical incision; in 11 a
      modified umbilical approach was used to facilitate delivery of the pyloric mass.
      Incisions are made in the skin fold of the upper half of the umbilicus and at the
      midline, joining the two at the top. The skin incision is closed by upper
      umbilical translocation with a very good cosmetic result. This incision allows
      easy access to the pylorus and provides more convenient exposure. The absence of
      traction on the retractors avoids tissue ischemia, which leads to wound abscess
      development.

PMID- 9156873
TI  - Transumbilical open laparoscopy: a simple method of avoiding complications in
      pediatric surgery.
AB  - The author reports his experience with a new procedure, transumbilical open
      laparoscopy (TUOL), to obtain the pneumoperitoneum in children operated upon
      laparoscopically. TUOL was designed to avoid complications related to closed
      introduction of the first trocar, and consists in the visually-guided
      introduction of the first trocar transumbilically without any need for a
      pursestring suture, with an operative time of about 1 min. The author recommends
      TUOL as it is easier, less expensive, and less time-consuming compared to other
      techniques.

PMID- 9156874
TI  - Reduction of scrotalized skin improves the cosmetic appearance of feminising
      genitoplasty.
AB  - A modified labioplasty to improve the cosmetic appearance after feminizing
      genitoplasty is described. Good results were obtained in all five patients in
      whom the technique was utilized.

PMID- 9156875
TI  - Association of ambiguous genitalia with VATER anomalies.

PMID- 9156877
TI  - History of pediatric surgery.

PMID- 9156876
TI  - Subcutaneously administered somatostatin analogue in traumatic pancreatic
      fistula.

PMID- 9156878
TI  - The history of hypospadias.
AB  - The dictum, "There is nothing new in surgery not previously described", is
      particularly true of hypospadias. The major significance of chordee was fully
      appreciated by Galen in the second century A. D. and then almost forgotten until
      Mettauer in 1842, all previous surgeons overstressing the position of the
      orifice. Mettauer recognised skin shortening as a cause of chordee, a fact not re
      discovered until 1967. Urethroplasty from penile skin in situ was well described
      by Thiersch in 1869 and Duplay in 1874; additional covering skin flaps were
      developed in 1892 by Lauenstein. The modern enthusiasm for pedicle tubes from
      prepuce was first employed by Van Hook in 1896, Rochet in 1899, Hamilton Russell
      in 1900, and Mayo in 1901; the "buried skin" technique of Denis Browne was
      described by Duplay in 1880, although attributed by Browne to Hamilton Russell in
      1915. Even scrotal tissues were incorporated in repairs in 1860 (Bouisson). Beck,
      in 1898, practised a repair for balanitic hypospadias very similar to the modern
      MAGPI repair, and free grafts, so popularised in the last 20 years, were
      performed by Nove-Josserand in 1897. We have certainly advanced from the era of
      the first millenium A. D., in which the treatment was amputation beyond the
      orifice, but almost all present-day techniques are well-founded in ideas
      developed by enterprising surgeons of the last century.

PMID- 9156879
TI  - Congenital posterior urethral obstruction: the historical perspective.
AB  - The currently accepted interpretation of urethral anatomy and pathology in boys
      is based on studies from the first half of this century, most notably from Hugh
      Hampton Young and his colleagues. The studies that led to Young's conclusions and
      the developments in the management allow for reinterpretation, particularly with
      the advent of prenatal diagnosis and video-endoscopic recording technology.

PMID- 9156881
TI  - [Echocardiographic evaluation of pulmonary artery flow parameters in patients
      with chronic pulmonary disease].
AB  - This study aimed at comparing the Doppler echocardiographic artery blood flow
      parameters in patients with and without chronic obstructive pulmonary disease
      (COPD), and estimating an effect of the present degree of airway obstruction on
      systolic functioning of the right ventricle. The study included 28 patients with
      COPD, and 22 patients without COPD constituting a control group. Pulmonary
      functional tests have been performed with the use of body plethysmography.
      Doppler echocardiographic assessment of the pulmonary artery flow included a
      measurements the acceleration time (AcT), and right ventricular ejection time
      (RVET). Both AcT and RVET have been corrected for the heart rate. Corrected AcT
      shorter than 100 ms has been considered specific for the pulmonary hypertension
      (PH). AcT in the studied group of patients ranged from 67 ms to 143 ms (mean 106
      +/- 21), and has been significantly shorter than that in the control group.
      However, no correlation between body plethysmographic findings and
      echocardiographic measurements has been found in COPD patients. Echocardiography
      is a sensitive technique detecting PH. As spirometric findings do not predict
      development of the cor pulmonale, Doppler echocardiographic evaluation of the
      blood flow in pulmonary artery may serve as a screening test.

PMID- 9156880
TI  - Historical aspects of congenital diaphragmatic hernia.
AB  - The first description diaphragmatic hernia appeared in 1575. In 1848, Bochdalek
      described congenital diaphragmatic hernia (CDH) occurring through a
      posterolateral defect. Successful surgical treatment of CDH in an infant was
      first performed in 1902, whereas the first neonate operated within 24 hours of
      life was reported in 1946. However, early surgery did not improve survival rates
      and the mortality was in the region of 50%. One reason for this was that more
      neonates underwent surgery who previously would have died without the repair of
      the CDH. Pulmonary hypoplasia and pulmonary hypertension were early recognised as
      important reasons for the high mortality rate. In recent years, an enormous
      effort has been made by research groups all over the world to describe the
      pathogenesis and pathophysiology of CDH, and apply these findings to clinical
      practice. Attempts have been made to define prognostic factors. Extracorporeal
      membrane oxygenation (ECMO) has produced encouraging results. Fetal surgical
      therapy remains an option in selected cases despite huge technical and ethical
      problems. Recently, several new therapeutic methods have been suggested, such as
      high frequency oscillatory ventilation, partial liquid ventilation, nitric oxide
      inhalation, surfactant therapy, and fetal tracheal ligation. However, more
      experience is required before the value of these approaches is clear. Despite
      these efforts, the mortality remains unacceptably high. The challenge for the
      future is to continue development of therapeutic approaches in order to improve
      survival of neonates with CDH.

PMID- 9156883
TI  - [Analysis of measurements: arterial blood pressure, pulse rate and oxygen
      saturation in arterial blood during broncho-fibroscopy and bronchoalveolar lavage
      in patients with bronchial asthma and chronic bronchitis].
AB  - Bronchial asthma and chronic bronchitis in stable period of disease could be an
      indication for diagnostic bronchofiberoscopy and broncho-alveolar lavage (BAL).
      30 patients with bronchial asthma (aged 27.2 +/- 9.3), 30 patients with chronic
      bronchitis (aged 55.9 +/- 11.0) and subjects of control group (aged 27.0 +/- 9.7)
      took part in this study. Selected parameters: heart rate (HR), arterial blood
      pressure (ABP) and arterial O2 saturation (SaO2) monitored by pulsoximetry were
      measured during the procedure. It was showed that broncho-fibroscopy and BAL
      could be performed safe in patients with asthma and chronic bronchitis as well.
      Bronchospasm was observed only in one subject with asthma. The highest decrease
      of saturation was observed during BAL in every investigated subject. Because of
      none of recorded parameters allows identification of the patients at risk of poor
      tolerance of the procedure, we propose close observation of patient, monitoring
      parameters: HR, ABP and SaO2, and oxygen supplementation during the
      investigation.

PMID- 9156882
TI  - [Bacterial flora of the respiratory tract in artificially ventilated patients].
AB  - Patients treated in ICUs are at particular risk for nosocomial infections. Within
      this group a ventilator-associated pneumonia still constitutes a major problem.
      Highly virulent hospital strains, existing in ICUs, can colonize patients' upper
      respiratory tract. Therefore this study aimed at analysing the organisms found in
      patients who required mechanical ventilation in ICUs. The same types of bacteria
      with the same (high) rate colonized upper airways, trachea and stomach of
      patients treated at the intensive Care Unit. It is suggested that the presence of
      Gram negative bacilli may serve as a marker of possible pneumonia in artificially
      ventilated patients. It is also important to check whether the organisms isolated
      from the larynx or trachea are only colonizing agents or are representative for
      the etiologic factors of pneumonia. Antibiotic therapy based on the sensitivity
      tests could be inadequate.

PMID- 9156884
TI  - [Clinical, radiologic and functional changes in the respiratory system and
      changes in cytology of bronchoalveolar lavage fluid of patients with idiopathic
      pulmonary fibrosis].
AB  - The course of the pulmonary fibrosis is difficult to estimate as there are no
      diagnostic tests specific and sensitive enough to assess disease activity.
      Together 33 patients with pulmonary fibrosis have been studied. They have been
      divided into 2 subgroups, depending on the intensity of clinical, radiologic, and
      functional disorders. In all patients bronchoalveolar lavage has been carried
      out, and the obtained results have been compared with those in 18 healthy
      individuals. Changes in the cellular composition of BAL fluid had polymorphic
      character. In the early phase of the disease, only percentage of lymphocytes in
      BAL fluid has been increased significantly whereas in the more advanced stage
      percentage of both neutrophils and eosinophils has also been significantly
      increased. The use of several parameters simultaneously helps to evaluate
      pulmonary fibrosis.

PMID- 9156885
TI  - [Respiratory system function in workers from the Mechanical Petrochemical Plant
      in Plock--influence of the workplace environment].
AB  - The aim of this study was to evaluate the influence of the work place environment
      on the function of the respiratory system. MATERIAL: Study covered 211 male from
      Mechanical Plant of Plock Refinery (M.P. group 1) and the control group consisted
      of 53 male employed in Design Office (D.O. Group II). Group I was exposed to
      toxic substances (NO2, SO2, dust, manganese and iron oxides). METHODS: Lung
      function tests were performed using laboratory "Compact-Lab" (JAEGER). The FVC,
      FEV1, FEV1%FVC, PEF, FEF50 were obtained from flow-volume curve and TGV, Rt
      measured using plethysmography method. Information concerning symptoms and
      cigarette smoking were obtained from questionnaire designed for this study.
      RESULTS: Mean values of respiratory indices were within normal range and did not
      differ between groups. The percentage of abnormal results was similar in groups.
      Air flow limitation (FEV1%FVC < 70%) was observed in 15.2% of total. Smokers have
      had significantly lower indies of air flow limitation but still within normal
      range. Symptoms (cough, expectoration, dyspnea) were equally frequent in M.P. and
      D.O. and significantly more frequent in smokers. CONCLUSION: In our study we did
      not find the influence of work place environment on the function of the
      respiratory system.

PMID- 9156886
TI  - [Specific IgE against inhaled allergens in dystreptic children with food
      allergy].
AB  - Immunoglobulin E specific for the selected inhalator allergens have been
      determined in 42 children with food allergy and failure to thrive, using tests
      and equipment 3M (Bio Whittaker). Co-existence of food allergy with
      hypersensitivity to inhaled allergens have been confirmed in 41 children (41%).
      An equivalent expression grade of IgE antibodies against food and inhaled
      antigens has usually been noted. Specific IgE produced in response to house dust
      and mixed feathers have been seen most frequently, and the first have been found
      in 37% of the tested children in the concentration exceeding 1.0 Ul/ml (2nd, 3rd
      and 4th class). The obtained results confirmed that specific IgE antibodies
      against inhaled allergens are being present in children who fail to grow and
      suffer from the food allergy. These findings should advocate further
      investigations in specific IgE antibodies to other groups of allergens.

PMID- 9156887
TI  - [Evaluation of selected immunologic indices in children with subglottic
      laryngitis].
AB  - Subglottic laryngitis (croup) is a common disease in children. Its etiology is
      not quite clear. Thirty children (28 boys and 2 girls), aged between 4 months and
      up to 5 years (mean 3.6 years), have been hospitalized for the inflammatory
      swelling of the subglottic space. Laboratory and allergy tests, including:
      immunoglobulins A, G, M, total IgE, specific IgE blood levels, blood T cell
      level, and NBT test have been carried out in all children. An increased IgE blood
      level have been noted in 15 (50%) children, and significantly increased blood
      level of specific IgE in 10 (33%) children of this subgroup. Blood IgA, IgG, and
      IgM level have been normal in all children. An increase in NBT test have been
      seen in 10 (33) children, and a decrease in the number of T cells in 21 (70%)
      children.

PMID- 9156888
TI  - [Studies on the use of music therapy as a form of breathing exercise in bronchial
      asthma].
AB  - 96 patients suffering was examined. 46 patients over one year was offending
      kinesytherapy during a special active music therapy techniques was used. It was
      the form of breathing exercises. 50 patients during the period of one year was
      under program of traditional breathing kinesytherapy. The authors observed a
      greater effectiveness of music therapy which decrease bronchial resistances,
      increases physical self-feeling and reduces anxiety level.

PMID- 9156889
TI  - [Deaths from asthma, bronchitis and pulmonary heart disease in Warsaw in the
      years 1993-1994].
AB  - By the regular checking the death certificates in the municipal offices in 7
      districts of Warsaw, the morality rate from asthma has been established as
      2.98/100.000, from chronic bronchitis as 8.71/100.000 and from pulmonary heart
      disease as 6.27/100.000. During one year of this survey only 15 deaths (4.7%)
      from these diseases were below age of 50.67% of patients died in hospitals and 22
      (7%) died suddenly (at home). In general, deaths reported as the results of COLD
      were only 1.59% of the total number of deaths in Warsaw (21.530). 6.9% of all
      death certificates were without clinical diagnosis (Number 798 of ICD)-described
      as "natural death", "death before doctor's arrival" or "noncriminal death".
      Authors discuss the problem of over- and under-diagnosis of asthma as the cause
      of death, the historical background of asthma mortality and also put the question
      of the righteousness of regard the pulmonary heart disease as the primary cause
      of death.

PMID- 9156890
TI  - [Fluticasone propionate in treatment of seasonal allergic rhinitis--open
      multicenter study].
AB  - Eighty five patients with seasonal allergic rhinitis, currently symptomatic, were
      treated with fluticasone proportionate nasal spray (Flixonase) in open,
      multicentre efficacy and safety study. The drug studied statistically significant
      decrease all but one (conjunctivitis) symptoms of the disease in the first week
      of treatment in the patient's and doctor's assessment. The full effect of
      treatment was revealed in the second week. There was significant protective
      effect observed during two weeks after the cessation of treatment. Adverse events
      were mild and occurred in two cases, due to disease itself rather, than the drug
      tested.

PMID- 9156891
TI  - [Results of immunotherapy with Allergovit preparation of the Allergopharma
      Company in patients with hypersensitivity to pollen].
AB  - It has been examined 72 patients with pollinosis in age from 5 to 38 which had
      immunotherapy by vaccines Allergovit. This vaccines has been composed to
      individual patients along there spectrum hypersensitivity to pollen. After one
      year hyposensibilisation 78.3% had a very good improve but 20.3% good. In them 7
      patients had symptoms in the time when has been pollen another plant than they
      has been vaccine. Only one hadn't improve because he had allergy to many pollen
      and vaccines which had too much allergen it's not effective.

PMID- 9156892
TI  - [A case of isolated lung contusion].
AB  - A case of the isolated lung contusion is presented. A possibility of such a
      trauma in young individuals with elastic thoracic covers has been noted. The
      necessity of chest X-rays within short period following trauma to detect a source
      of contusion is stressed because of the dynamic changes in the contused lung
      tissue. Proper treatment produces a remission of pathologic lesions in lung
      parenchyma within 4-10 days.

PMID- 9156893
TI  - [Lung lipoproteinosis--diagnostic problems].
AB  - Pulmonary alveolar proteinosis is a very rare disease, first described by Rosen
      in 1958. It is characterized by the accumulation of lipoproteins in the pulmonary
      alveoli. Clinical and radiologic presentations are typical for the interstitial
      lung disease. Only few cases of this disease have been described in the Polish
      literature. A patient with disseminated lesions to the lungs is presented. A
      diagnosis was possible after an analysis of BAL fluid and histological
      examination of the lung tissue collected by the transbronchial biopsy.

PMID- 9156894
TI  - [Pulmonary infarction as a complication of thrombotic changes in an arteriovenous
      fistula of a patient with terminal renal insufficiency treated with long-term
      hemodialysis and recombinant human erythropoietin].
AB  - The case of 48 year old female patient with terminal renal insufficiency treated
      with hemodialysis and human recombinant erythropoietin was observed because of
      pulmonary infraction. The symptoms of disease were observed in the right lung and
      in region of arteriovenous fistula. It was documented that therapy with human
      recombinant erythropoietin may induce thrombosed complications during
      hemodialysis with arteriovenous fistula.

PMID- 9156895
TI  - [Tuberculosis of the bones and joints].
AB  - The incidence of tuberculosis has increased over the last several years. Bones
      and joints tuberculosis makes 20% of all extrapulmonary locations of
      tuberculosis. In Poland this form of tuberculosis is underdiagnosed. We present
      three cases with tuberculosis of bones, joints and lung to remind the basic
      principles of diagnosis and treatment.

PMID- 9156896
TI  - [Disorders of respiration during sleep].

PMID- 9156897
TI  - [Spinal tuberculosis].
AB  - The cases of 32-year-old man and 42-year-old women are presented. Their history
      illustrates difficulties in the diagnosis of tuberculosis of the vertebral
      column. The patients suffered significant pains in the lumbar region lasting one
      year. Despite the presence of some abnormalities in lumbar vertebrae on x-rays no
      examinations were ever performed to establish the diagnosis. Lumbago and
      osteoporosis were considered as the cause of complaints. Aetiology was confirmed
      only when patients developed disseminated tuberculosis of the lungs.
      Antituberculous chemotherapy was successful and brought a fast improvement in
      general status of the patients.

PMID- 9156898
TI  - [Pathogenetic basis of treatment for chronic obstructive pulmonary disease].
AB  - The pathological reactions are discussed as a basis of applied therapy in
      patients with chronic obstructive pulmonary disease. The pharmacokinetic
      mechanisms of contemporary used drugs are presented with indication of
      interaction in allergic reaction.

PMID- 9156899
TI  - [Management of respiratory failure in the neonate].

PMID- 9156900
TI  - [The role of interferon-gamma and interleukin-4 in the pathogenesis of atopic
      diseases].
AB  - The role of interferon-gamma and interleukin-4 are presented according to actual
      knowledge in this field. Some clinical implication indicate an importance of
      above mentioned proteins in reactions observed in patients with atopic diseases.

PMID- 9156901
TI  - [Clinical course and treatment of acute poisoning caused by some mushrooms].
AB  - Mushroom poisonings are discussed in the paper. Clinical picture and applied
      treatment are presented with characterisation of the most toxically species for
      human being.

PMID- 9156902
TI  - [Henry Sienkiewicz and the Warsaw laryngologists].

PMID- 9156903
TI  - [Chronic alveolar hypoventilation in obstructive sleep apnea syndrome].
AB  - Among 30 patients with obstructive sleep (OSA) syndrome in 15% (50%) chronic
      alveolar hypoventilation developed; chronic hypercapnia was found in patients
      with mildly (7), moderately (2) and severely (6 patients) impaired lung
      ventilatory function. All patients with chronic hypercapnia were morbidly obese
      (BMI 44 +/- 12). Nocturnal polysomnography showed similar mean apnea duration in
      the groups of hypercapnic and eucapnic patients, longer duration of the longest
      apneas in hypercapnia (88 +/- 42 s) than in eucapnia (38 +/- 19 s), p < 0.01 and
      more severe desaturation during sleep (the mean of the lowest SaO2 during apneas
      0.46 +/- 0.17 mol/mol) in hypercapnic and 0.71 +/- 0.11 mol/mol in eucapnic
      patients, p < 0.001). Polycythemia was found in 14 patients, exclusively in
      hypercapnia. CONCLUSIONS: Chronic alveolar hypoventilation develops in some obese
      patients with impaired-even mildly or moderately-lung ventilatory function and
      with the most severe OSA syndrome, in which apneas may occasionally be extremely
      long and lead to very low saturation during sleep. Polycythemia occurs in most
      patients with chronic alveolar hypoventilation and OSA syndrome.

PMID- 9156904
TI  - [Mortality of patients with myocardial infarction at a young age].
AB  - Among patients with myocardial infarction, patients up to 40 years of age
      accounted for 5.1% (5.4% men and 4.1% women). Early mortality due to myocardial
      infarction was in the all material 42.6% and depended mainly on deaths of men in
      the prehospitalization period. Prehospitalization mortality varied between men
      and women. It was 45.3% for men and 11.2% for women. Hospital mortality was low,
      accounting for 7.8% of the treated subjects.

PMID- 9156905
TI  - [Evaluation of efficacy and mechanism of action of angioplasty and directed
      atherectomy assisted by intravascular ultrasonography].
AB  - Intravascular ultrasound (IVUS) is a unique method of coronary lumen
      visualization enabling also examination the structure of the artery wall. Aim of
      this study was to assess efficacy and mechanisms of action of balloon angioplasty
      (PTCA) and directional atherectomy by means of IVUS. IVUS examination was
      performed before and after mechanical revascularization procedure in 37 pts (DCA
      19 pts, PTCA-18 pts). Both PTCA and DCA resulted in enlargement of the coronary
      artery lumen (2.29 +/- 1.19 mm2 vs 2.93 +/- 1.55 mm2) but, also external diameter
      of the vessel increased after the procedure (1.94 +/- 1.10 mm2 and 0.74 +/- 1.01
      mm2 retrospectively). In 55.6% of cases after PTCA plaque rupture or artery wall
      dissection was observed, mainly in eccentric lesions (70%). IVUS allowed to
      recognize details of artery lumen and define efficiency of procedure. In about
      15% cases decision to continue PTCA or DCA was made on the basis of IVUS images
      only. The mechanism in which PTCA modifies the artery lumen is diverse and
      depends on the structure of lesion. Factors possibly responsible for enlargement
      of the lumen are: stretching, squeezing and translocation of atheroma as well as
      cracking and dissections along the arterial wall. DCA effectiveness depends on
      the withdraw of the atheromatous deposit, however, in over one-half of cases also
      stretching has some effect.

PMID- 9156906
TI  - [Studies of fibromuscular hyperplasia of vascular anastomosis].
AB  - The aim of this study was to present a retrospective analysis of occurrence,
      diagnosis, methods and treatment results in patients treated because of
      thrombosis of vascular anastomosis. Authors have tried to make and experimental
      model of hyperplasia of vascular anastomosis and verify a possibility of stop
      hyperplasia application by an optimal dose of dexamethasone. They also have
      evaluated an efficacy of Doppler color ultrasonography to make an early diagnosis
      of stenosis of vascular anastomosis.

PMID- 9156907
TI  - [Echocardiographic evaluation of left ventricular function in patients with
      chronic renal failure treated with intermittent peritoneal dialysis].

PMID- 9156908
TI  - [Equivalent occlusion of the left main coronary artery--case report].
AB  - In the paper two cases are described of patients in whom during angiography
      coexistent occlusion of the left descending artery and left circumflex artery was
      found. ECG and echocardiography in both cases were not indicating such a high
      coronary vessel defect. In both patients angiography was performed leading in one
      case to development of shock with fatal outcome.

PMID- 9156909
TI  - [Arterial hypertension caused by abnormality and translocation of the kidney].
AB  - The authors described developmental anomaly of the right kidney associated with
      hypertension and pyonephrosis in a 37 years old male. The authors reported the
      diagnostic problems in this kind of hypertension. After nephrectomy had been
      performed the elevated blood pressure returned to normal values without any
      additional pharmacological treatment.

PMID- 9156910
TI  - [Beta-adrenergic receptor blockers in the treatment of chronic heart failure].
AB  - We present a current opinion about the management of chronic heart failure with
      beta-blocking agents. Pathophysiologic rationales for such treatment and clinical
      experience were analyzed. Most of the studies showed that long-term treatment of
      heart failure with beta-blockade produces improvement in symptoms, exercise
      tolerance, ejection fraction and central hemodynamics (CI, PCWP, MPAP, LVSWI,
      SVI). Treatment must be started at an extremely low dose and then must be
      increased gradually to therapeutic levels over several weeks. The titration phase
      must take place in the hospital. It was emphasized that the management of chronic
      heart failure with beta-blockers is not the routine management yet. Ongoing
      multicenters trials should finally determine the place of beta-blockers in the
      treatment of chronic heart failure.

PMID- 9156911
TI  - [Imidazoline receptors and use of drug blocking receptors I1].
AB  - Imidazoline-preferring receptors are important in the pathophysiology of
      hypertension. The selective l1-receptor agonists are moxonidine, cimetidine and
      rilmenidine. Some clinical studies indicate the usefulness of moxonidine therapy
      in hypertension, arrhythmias and acute myocardial infarction.

PMID- 9156912
TI  - [Early exercise test in patients with myocardial infarction after nifedipine
      administration of prolonged duration].
AB  - In 25 patients with transmural myocardial infarction a mean of 16 days after the
      onset of infarction an exercise stress test was performed 2 hours after the
      administration of Corinfar Retard. We evaluated ECG, blood pressure, heart rate,
      echocardiograms and spirographic parameters before and after drug administration.
      In the majority of patients ST segment depressions were reduced and duration of
      the exercise test increased or remained unchanged. In 5 patients the magnitude of
      ST segment depression was markedly decreased and associated with prolonged
      duration of exercise and substantial patient comfort. In these patients the drug
      is continued, as its withdrawal resulted in decreased exercise tolerance with
      accompanying chess discomfort. Corinfar Retard significantly decreased weigh
      blood pressure, both systolic and diastolic, whereas its effect on low blood
      pressure was only slight or none. Heart rate was higher before exercise, during
      and after exercise it did not differ from that measured without the drug.
      Ejection fraction increased by a mean of 4%; VC and FEV1 increased or remained
      unchanged. Exercise testing was safe, did not produce and any side effects and
      seems to be useful in deciding about the choice of drug after myocardial
      infarction, especially in patients with counterindications to beta blockers.

PMID- 9156913
TI  - [Treatment of patients after myocardial infarction].
AB  - During the first year after myocardial infarction 15-20% of patients die and
      about 50% because of sudden death. Appropriate therapy is essential to prevent
      arrhythmias and heart failure. Some pharmacological methods are discussed in main
      clinical aspects.

PMID- 9156914
TI  - [Blood platelets and fibrinolysis in ischemic heart disease].
AB  - The role of platelets and fibrinolysis in ischemic heart disease are discussed.
      The interaction lipoproteins with platelet factors may be important in therapy of
      ischemic heart disease.

PMID- 9156915
TI  - [Use of recombinant DNA technique in circulatory system diseases. A short outline
      of recombinant DNA methods].

PMID- 9156916
TI  - [Use of recombinant DNA techniques in circulatory system diseases. Use of DNA
      analysis for evaluating diseases of circulation].

PMID- 9156917
TI  - [The influence of biometeorologic conditions on morbidity].
AB  - Connection between morbidity and biometeorological changes has been analyzed.
      Special stress was paid on diseases of the circulatory system.

PMID- 9156918
TI  - [Levels of calcium, magnesium, zinc, copper and iron in hair of children and
      adolescents].
AB  - Hair calcium, magnesium, zinc, copper, and iron levels have been determined in
      420 children and adolescents, aged between 5 and 18 years, and inhibiting
      Szczecin area. Levels of these bioelements have been assayed with atomic
      absorption spectroscopy. Mean magnesium and calcium levels in hair of children
      from Szczecin area are higher than those in other regions of the country.
      Magnesium, calcium and zinc levels have been the lowest in hair of children aged
      between 5 and 9 years, increased with the age, achieving the highest values in
      adolescents aged between 15 and 18 years. In a 5-year age groups, hair magnesium
      and calcium levels have been higher in girls than in boys.

PMID- 9156919
TI  - [An overview of new management guidelines and treatment of essential
      hypertension].

PMID- 9156920
TI  - [Molecular basis of hypertrophic cardiomyopathy].

PMID- 9156921
TI  - [Arrhythmia in patients with hypertrophic cardiomyopathy during an exercise test
      with 24-hour Holter monitoring].
AB  - Thirty patients with hypertrophic cardiomyopathy (HCM), (20 men and 10 women, age
      16-55, mean 37 +/- 8 years) underwent exercise test done on bicycle twice to
      estimate effort tolerance before drugs. In all patients a 24-hour ekg Holter
      monitoring was also performed. During exercise test heart rhythm disturbances
      were noticed in 2 patients (7%). One had a 2-second sinus arrest, in the other
      ventricular bigeminity was observed. Twenty two patients (79%) had rhythm or
      conduction disturbances in Holter monitoring. In 2 (7%) rhythm generation and
      conduction abnormalities, in 7 (23%)-supraventricular and in 13 (43%)-ventricular
      arrhythmia. Ten of them (33%) had Lown class IVa and IVb arrhythmia. In
      conclusion we suggest that exercise test done on bicycle ergometer is a safe
      method to estimate effort tolerance in patients with HCM and usually does not
      induce rhythm disturbances. Holter monitoring is more effective than exercise
      test in revealing cardiac arrhythmia.

PMID- 9156922
TI  - [Silent myocardial ischemia before and after revascularization].
AB  - In 82 patients with unstable ischemic heart disease (IHD) before and after
      revascularisation (percutaneous transluminal coronary angioplasty-PTCA-in 11
      patients and coronary artery bypass graft-CABG-in 71 patients) silent ischemia
      incidence was observed. In these patients before and after operation election
      fraction (EF) and wall motion score index (IK) were compared
      echocardiographically as well as physical ability according to Bruce protocol in
      treadmill exercise test. Data (EF and IK and exercise test) before and after
      operation didn't change significantly. Silent ischemia was directed before
      operation in 17 patients (21.8%) and in 15 patients (19.4%) one month after those
      procedures.

PMID- 9156923
TI  - [Qualifying patients with unstable angina for invasive tests based on
      electrocardiographic examinations].
AB  - In 40 patients with unstable angina pectoris a variety of electrocardiographic
      parameters were analysed. In all patients routine ECG, signal averaged high
      resolution ECG. 24 hour ECG recordings and heart rate variability analysis were
      performed at admission and repeated at 7 day of hospitalization. During second
      week patients underwent also exercise treadmill test. On basis of clinical
      presentation each patient was qualified to invasive investigation, 31 patients
      had need for urgent cardiac catherization (group I-urgent indications) and in the
      remaining 9 patients cardiac catherization was performed 3 months after the
      relief of acute symptoms (group II-non-urgent indications). The most impressive
      implications were draw from repeated 24 hour Holter ECG monitoring. In patients
      with urgent indications (gr. I) more frequent and severe ischemic episodes, as
      well as more frequent ventricular arrhythmias were observed. Patients from group
      I were unable to achieve higher grades on exercise treadmill test, while ST
      segment depression was comparable in both groups. Heart rate variability analysis
      showed greater disturbances of cardiac vagal control in group I. The number of
      critically stenosed vessels was similar in both groups, however left ventricular
      systolic dysfunction was observed mainly in patients with urgent indications for
      cardiac catherization.

PMID- 9156924
TI  - [The effect of paroxysmal atrial fibrillation during ischemic heart disease on
      parameters of atrial signal-averaged electrocardiography].
AB  - The aim of this study was assess the correlation between duration of paroxysmal
      atrial fibrillation (PAF) during ischemic heart disease (IHD) and atrial signal
      averaged electrocardiogram (ALP). The study population consisted of 75 patients
      with PAF during IHD whose were divided according to duration of PAF into three
      groups; gr. I- < 1 year, gr. II-1-5 years, gr. III- > 5 years. The control group
      (gr. IV) composed of 50 healthy. Recording of ALP were carried out by HIPEC-200
      HA. We calculated time domain parameters of ALP; root mean square voltage of the
      signals in the last 10, 20 and 30 ms of the filtered P-wave and filtered P-wave
      duration. During frequency analysis of ALP we calculated frequency parameters in
      range from 40 to 400 Hz in linear scale; area ratio 20-50/0-20 Hz and marked the
      highest peak amplitude of signals and in logarithmic scale; defined energy
      spectra of frequency component > -60 dB and value of frequency component 40 Hz.
      Our results suggest that: 1. The values of root mean square voltage of the
      signals in the last 10 ms of the filtered P-wave have been decreasing according
      to passage of duration PAF. 2. Patients with longer anamnesis of PAF have had
      longer duration of filtered P-wave. 3. Proposed parameters of frequency analysis
      of ALP in both scales (linear and logarithmic) seemed useless in differential
      diagnosis of patients with PAF during IHD and healthy.

PMID- 9156925
TI  - [Correlations between left atrial size and parameters of averaged atrial signal
      in patients with paroxysmal atrial fibrillation in the course of ischemic heart
      diseases].
AB  - The aim of this study was to assess the correlation between left atrial size and
      atrial signal-averaged electrocardiogram (ALP) in time-domain and frequency
      analysis in patients with paroxysmal atrial fibrillation (PAF) during ischaemic
      heart disease (IHD). The study population consisted of 75 patients with PAF
      during IHD who were divided into two groups; gr. I (left atrial dimension 40 mm)
      and gr. II (left atrial dimension 40 mm). The control group (gr. III) consisted
      of 50 healthy subjects. Recording of ALP was carried out by HIPEC-200HA. The high
      gain ECG was recorded during basic rhythm with orthogonal Frank leads X,Y,Z.
      These signals were amplified, averaged and filters. The filtered signals were
      combined into a vector magnitude and time-domain and frequency analysis was done.
      These findings suggest that the size of the left atrium does not change time
      domain and frequency parameters of ALP in patients with PAF and IHD. We noticed
      significant influence of IHD on these parameters. On the other hand frequency
      analysis of ALP did not show any uselessness in diagnostic identification of
      patients with PAF during IHD and healthy subjects.

PMID- 9156926
TI  - [The frequency of resuming work among patients with ischemic heart disease after
      the second phase of rehabilitation].
AB  - The aim of the study was to evaluate the frequency of resuming work among IHD
      patients after stationary posthospital rehabilitation. 30 patients after MI and
      revascularisation operations were taken into consideration: A-13 patients who
      resumed work and B-17 who did not do so. 30 healthy, working men (KZ) were used
      as a control. ECHO and exercise tests were carried out before and after
      rehabilitation. The following parameters were analysed: EF%, and HR, SBP, DBP and
      Dp both rest and exercise, Lt (wat), VO2 and MET, EF% was found to be lower in A
      and B groups compared to KZ. In both study groups physical efficiency before
      treatment was low, but after rehabilitation there was a significant increase in
      efficiency parameters. Consequently, the A group were classified in medium
      levels, whereas group B remained in low efficiency class. VO2, MET and Lt after
      rehabilitation in A group were significantly higher compared to those in the B
      group. 43% of all patients tested resumed work. People with higher education
      prevailed in the group who resumed work.

PMID- 9156927
TI  - [Remodeling of the left ventricle after myocardial infarction].
AB  - Cardiac remodeling following myocardial infarction denotes changes of left
      ventricular shape, chamber size and wall thickness. It involves both the
      infarcted and the noninfarcted segments. This process begins at the time of acute
      myocardial infarction, progresses by stages, and can lead to congestive heart
      failure. The major determinants of lest ventricular remodeling are infarct size
      and transmural, adequacy of the healing process, mechanical deformation forces,
      and progressive ventricular dilation. Infarct expansion is a relatively frequent,
      early occurring alteration of the ventricular shape. It denotes thinning and
      lengthening of the infarct segment. The progressive ventricular remodeling can be
      halted by reactive hypertrophy of the viable myocytes, on condition that it is
      appropriate. The left ventricular increase results from myocytes hypertrophy,
      partly their hyperplasia, and increase of fibrosis. Major ways of action in order
      to limit the cardiac remodeling after myocardial infarction are: reperfusion of
      the infarct-related vessel by thrombolysis, nitrate therapy, and angiotensin
      converting enzyme inhibitors administration. Maximum benefit is when therapy is
      begun very early.

PMID- 9156928
TI  - [The effect of specific immunotherapy on the concentration of some chemokines in
      BALF in patients with atopic bronchial asthma].
AB  - The cellular basis the mechanism of specific hyposensitization is still unclear.
      We studied the effect of immunotherapy on activity of interleukin-8 (IL-8) and
      monocyte activating and chemoattractant protein (MCAF/MCP1) in bronchoalveolar
      lavage fluid (BALF). 20 patients with atopic asthma took part in this study. 14
      were treated with grass pollen extracts (Allergovit, Allergopharma, Germany) for
      7 weeks and 6 of this group were not treated and served as control group. ELISA
      test (R&D, USA) was used to assess IL-8 and MCAF/MCP1 activity in one ml of BALF
      recovered before and after immunotherapy. The results indicate that immunotherapy
      induces the suppression of MCAF/MCP1 production and the increase of IL-8
      production in BALF. These chemokines may have reciprocal control on inflammatory
      cells, which participate in creating of inflammatory changes in asthma.

PMID- 9156929
TI  - [Fibrocystic disease of breast and pituitary-thyroid axis function].
AB  - The aim this study was to report findings on the concentrations of mean
      triiodothyroxine (T3), thyroxin (T4), thyroid stimulating hormone (TSH) and
      prolactin (Prl) in patients with benign mastopathy and in control group. All of
      the examined subjects were clinically euthyroid. The mean T4 concentrations in
      women with mastopathy (78.25 +/- 15.27 ng/ml) were significantly lower than in
      control group 88.73 +/- 15.27). The mean TSH and PRL concentration in women with
      mastopathy were higher, but not significantly, than in control women. This
      results indicate, that benign mastopathy seems to be connected with thyroid
      functions.

PMID- 9156930
TI  - [1000 quadrantectomies--personal experience].
AB  - Analysis of 1000 quadrantectomies performed because of malignancy suspicion has
      been carried out to evaluate the long-term results of this method. Authors
      underline that only 5% of patients with breast cancer was able to be qualified to
      quadrantectomy.

PMID- 9156931
TI  - [Effect of deferoxamine on erythropoiesis in patients hemodialyzed for chronic
      renal insufficiency treated with erythropoietin].
AB  - The aim of the study was to evaluate the effect of deferoxamine therapy on
      erythropoiesis, aluminium concentration and iron metabolism in hemodialyzed
      patients with chronic renal insufficiency treated with human recombinant
      erythropoietin (Eprex, Cilag). 8 hemodialyzed patients (2 female and 6 male) in
      long-term programme with aluminium serum concentration over 160 micrograms/l were
      treated with deferoxamine (5 mg/kg b.m.) during the last hour of hemodialysis in
      slowly intravenous infusion since 1 months. During this treatment aluminium and
      iron serum concentrations, serum iron-binding capacity, transferrin and
      hematocrit were determined before and after 1 months of deferoxamine therapy. The
      significant decrease of aluminium serum concentration (p < 0.05) and increase of
      hematocrit (p < 0.01), iron (p < 0.05) and serum iron-binding capacity (p <
      0.001) were determined. The results of performed analysis indicate that aluminium
      is able to inhibit erythropoiesis induced by erythropoietin. The improvement in
      erythropoiesis and iron metabolism after deferoxamine therapy was observed.

PMID- 9156932
TI  - [Tissue plasminogen activator and inhibitor and the severity and extensiveness of
      vascular lesions in peripheral atherosclerosis of the legs].
AB  - The aim of work was to study whether activity and antigen level of tissue
      plasminogen activator (t-PA) and activity of plasminogen activator inhibitor (PAI
      1) were related to severity and extensiveness of vascular lesions in peripheral
      obliterative atherosclerotic disease (POAD). The study group consisted of 25
      patients in II (13), III (10) and IV (2) degrees of disease acc. to Fontaine'a.
      In the blood t-PA activity and antigen and activity of PAI-1 were determined. In
      the patients with more severe POAD higher t-PA antigen and increased t-PA
      complexed with PAI-1 were observed. In patients with unisegmental POAD twice t-PA
      activity than in patients with polysegmental atherosclerotic lesions was
      detected.

PMID- 9156933
TI  - [Diagnostic value of cytologic examination of urine sediment in patients with non
      neoplastic diseases].
AB  - The results are presented of urine sediment cytological examination of all
      patients treated in the Department of Urology for non-neoplastic diseases from
      March 01, 1989 to October 01, 1991. Out of the total number of 936 newly admitted
      patients in 88 cases the urine cytological examination demonstrated dysplastic
      cells which accounted for 9.4%, while in 11 cases cells suspected of malignancy
      were found which accounted for 1.2%. These patients are under constant urological
      control.

PMID- 9156934
TI  - [Favorable effects of epsilon-aminocaproic acid on the children with nephrotic
      syndrome and Schonlein-Henoch syndrome treated with corticosteroids].
AB  - An effect of EACA given in the daily dose of 85-230 mg/kg for 1-1-days on the
      activity of certain plasma protease inhibitors in 7 children with steroid
      sensitive and steroid-dependent nephrotic syndrome (age between 3.5 and 18
      years), and in 6 children with Schonlein-Henoch syndrome (aged between 3.5 and 6
      years). Additionally, an effect of EACA on clinical status, dynamics of
      improvement, proteinuria and/or erythrocyturia, and incidence of adverse
      reactions was studied. It was found that EACA significantly increased
      antithrombin III activity by approximately 68.8% proteinase alpha 1-inhibitor by
      41.8% alpha 2-antiplasmin by 55% in patients with nephrotic syndrome, and
      increased an activity of protease alpha 1-inhibitor by 75% in patients with
      Schonlein-Henoch syndrome. EACA given together with corticosteroids enhanced
      their efficiency manifested--especially in children with Schonlein-Henoch
      syndrome--by a rapid diminishment of skin changes, proteinuria and
      erythrocyturia. A drop in blood pressure, loose stools, upper respiratory
      inflammation, and fever were most frequent adverse reactions. EACA given alone
      produced rapidly increasing edema in patients with hephrotic syndrome. It seems
      that EACA may be used as an adjuvant therapy in some cases of nephrotic and
      Schonlein-Henoch syndromse.

PMID- 9156935
TI  - [An effect of chromatographic fraction ultrafiltrate of plasma on aggregation of
      blood platelets in patients with chronic uremia].
AB  - Chromatographic separation of ultrafiltrates from uremic patients on Sephadex A25
      has showed that medium molecular weight substances were prior to the dialysis
      contained in 2 peaks in 6 patients, and in a single peak in 14 patients. The same
      substances were contained only in one peak after dialysis. Substances contained
      in the first peak inhibited blood platelets aggregation produced by ADP. Dialysis
      decreased this inhibitory effect.

PMID- 9156936
TI  - [Evaluation of vaccine potency against viral hepatitis B performed with HB-vax II
      vaccine in a group with an increased risk for hepatitis B].
AB  - The aim of this investigation was to established the rate of seroconversion
      against hepatitis B after vaccination of workers of the National Institute of
      Cardiology who are at increased risk. All participants were HBs-Ag, and anti-HBs
      negative and also had normal standard hepatic laboratory tests. Vaccination was
      carried out according to following scheme: the first vaccination at t = 0, the
      second after one month and the third after six months. Vaccine was given
      intramuscular. The success of vaccination was monitored by the quantitative
      determination of antibodies against HBs-Ag (Anti-HBs) by the ELISA method
      (Abbott). After each vaccination, anti-HBs formation above 10 iu/l protective
      level was observed in 40.7%, 85.9%, and 97.1% of immunocompetent subjects after
      first, second, and third vaccination respectively. The acquired anti-HBs titer
      varies from individual to individual but in immunocompetent subjects the level of
      antibodies against HBs after third vaccination was 170 fold higher then those
      after first vaccination. These results seems to suggest that vaccine HB-Vax-II is
      effective and may by recommended in pre-exposure prophylaxis against hepatitis B.

PMID- 9156937
TI  - [Microbiologic state of the vagina in labor and puerperal fever].
AB  - Vaginal smears have been collected from 520 delivering women for bacteriological
      evaluation and analysis of the relationship between present organisms with
      puerperal fever. A relationship between the composition of vaginal flora before
      labour and pathological organisms isolated during puerperal fever has been shown.
      Presence of the exogenous source of infections has also been confirmed.

PMID- 9156939
TI  - [Puerperal infection of the urinary tract].
AB  - An urine routine and bacteriological analysis was performed in 100 female
      patients in third "trimester" of pregnancy and in the second day after delivery.
      When bacteriuria was detected a next urine bacteriological examination was done
      in 8-10 and 30-50 days after the delivery. A rate of bacteriuria in female
      patients before the delivery was 33% and after 56%. The results of routine urine
      analysis were in normal limits in 31.1% of females with significant bacteriuria.
      A spontaneous disappearance of bacteriuria between 8 and 50 day after the
      delivery was observed in 46.6% of patients, but in 53.4% symptoms of urinary
      tract infection were noticed. Escherichia coli (serotype A and B) was defined in
      79.3% of observed urinary tract infections.

PMID- 9156938
TI  - [Presence of autoantibodies in patients infected with HIV].
AB  - The presence of serum autoantibodies directed against single-stranded DNA
      (ssDNA), RNA, histones, nuclear antigen SS-A, mitochondria and cardiolipin were
      investigated in 30 HIV-negative drug addicts (from years 1986-87), 30 addicts
      actually infected with HIV and 31 AIDS patients presenting with clinical symptoms
      indicating autoimmune disorders. Positive results were found in 12 (40%) drug
      addicts from years 1986-87, 5 (16.7%) actually infected and 16 (51.6%) AIDS
      patients. Autoantibodies were more often detectable in patients with
      thrombocytopenia 8/12 (66.7%) than in remaining 8 out of 19 subjects (42.1%) who
      presented dermatitis, hepatitis, pancarditis, ulcerative colitis and
      polyneuropathy. The prevalence of autoantibodies in all investigated groups were
      significantly higher than in controls-1/20 (3.3%).

PMID- 9156940
TI  - [The risk of surgical treatment in elderly patients].
AB  - The course of surgical treatment of 124 patients aged over 70 years was subjected
      to an assessment. On the basis of the ASA classification, 88% of all surgically
      treated patients fell into group III-IV of risk. Surgical operations were
      performed under intratracheal general anaesthesia (85%) or conduction anaesthesia
      (15%). The induction of general anaesthesia was accompanied by adverse reactions
      of the cardiovascular system in the form of arterial blood pressure drops and
      heart rhythm disturbances. Heart rhythm disturbances were not observed in
      patients under conduction anaesthesia. No intraoperative deaths were noted.

PMID- 9156941
TI  - [Surgical results of osteosynthesis in fracture of the mandible].
AB  - In the study the results of osteosynthesis in fracture of the mandible with
      miniplates and osteosuture. The 80 patients in two groups with 40 subjects in
      each were suffering from fracture of the mandible. In 25 of them the miniplate
      osteosynthesis was performed. The healing of wound, functional evaluation and the
      state of postoperative scar were described. Complication in both examined groups
      were similar. No difference was noticed in size and picture of scars after
      miniplate osteosynthesis and osteosuture. In 62.5% of miniplate osteosynthesis
      the intraoral way was used to diminish the postoperative scar. The good results
      of this method indicate an usefulness in clinical practice.

PMID- 9156942
TI  - [Renal protective effects of calcium antagonists].
AB  - Calcium antagonists (C-A) induce different, renal hemodynamic alterations. They
      reduce afferent arteriolar resistance and do not change glomerular filtration
      rate. C-A prevent acute renal failure, especially after kidney transplantation.
      Calcium antagonists decrease nephrotoxicity of cyclosporine and radiocontrast
      media. C-A are recommended in the therapy of renovascular hypertension.

PMID- 9156943
TI  - [Results of tamoxifen treatment in patients with advanced breast cancer].
AB  - The results of advanced breast cancer therapy with tamoxifen have been evaluated.
      The objective response to the drug has been achieved in 32 (31.7%) patients, and
      a 2-year survival in 52% of cases. A correlation between the localization of
      lesions and response rate has been found. The best results have been achieved in
      localized lesions and lymph nodes metastases. Low toxicity of the drug enables
      achievement of results comparable to those seen in all types of the hormonal
      therapy, except androgens.

PMID- 9156944
TI  - [Alveolar thyroid cancer with Hurthle cells in a 12-year old boy].
AB  - Thyroid cancer has been diagnosed of 12-yrs old boy. The consentive surgery was
      performed and good results were observed.

PMID- 9156945
TI  - [A case of HELLP syndrome complicated by acute renal failure and acute
      respiratory failure].
AB  - We present a case of HELLP (haemolysis, elevated liver enzymes, low platelets)
      syndrome that developed post partum in 31 year old woman. It was initially
      misdiagnosed as acute cholecystitis. The disease was complicated with acute renal
      failure and acute respiratory failure. Admission to the intensive therapy unit
      became necessary; patient required haemodialysis and short lasting mechanical
      ventilation. The outcome of described case was nevertheless good.

PMID- 9156946
TI  - [Primary non-Hodgkin's lymphoma of the prostate].
AB  - A patient with a rare primary lymphoma of the prostate is presented. Clinical
      symptoms may be a reason of mistake, that are highly suggestive of benign
      prostatic hyperplasia or prostatic adenocarcinoma. Before treatment all patients
      should have to determined the histopathological diagnosis (made by prostatic
      biopsy or by prostatectomy) because treatment of patients with primary non
      Hodgkin's lymphoma of the prostate is quite different then treatment of patients
      with prostatic adenocarcinoma. After treatment with combination chemotherapy
      appropriate for the clinical stage and the specific histological subtype our
      patient achieved a complete remission and remained free of disease after twelve
      months.

PMID- 9156947
TI  - [Syndromes of thyroid hormone resistance].
AB  - The authors have presented the contemporary knowledge concerning the syndromes of
      thyroid hormone resistance. There are three forms of this syndrome: Generalized
      Resistance of Thyroid Hormone, Pituitary Resistance to Thyroid Hormone and
      Peripheral Tissue Resistance to Thyroid Hormone. The illness appears in both
      family and sporadic forms. Etiology with the special concern to the molecular
      level is presented. The authors have also characterized the clinical picture,
      diagnostic methods and treatment of the syndrome.

PMID- 9156948
TI  - [Cooperation of proinflammatory interleukins in a cytokine rete in patients with
      septic syndrome].

PMID- 9156949
TI  - [The role of delusions].
AB  - Delusions are psychopathological symptom observed in plenty of psychical
      diseases. The role of this changes is presented in different pathologies.

PMID- 9156950
TI  - [Position of the Principle Board of the Polish Allergy Society on unconventional
      methods of diagnosis and treatment].

PMID- 9156951
TI  - [Decision by the Principle Board of the Polish Allergy Society].

PMID- 9156953
TI  - Proceedings of the 1996 Joint Symposium on Clinical Trial Design in Periodontics.
      Bethesda, Maryland, January 30-February 2, 1996.

PMID- 9156952
TI  - [Bioresonance therapy. MORA therapy. BICOM (biocommunication)].

PMID- 9156954
TI  - A case of membranous glomerulonephritis associated with Recklinghausen's
      neurofibromatosis.

PMID- 9156955
TI  - Patient compliance and therapeutic coverage: amlodipine versus nifedipine SR in
      the treatment of hypertension and angina: interim results. Steering Committee and
      Cardiologists and General Practitioners involved in the Belgium Multicentre Study
      on Patient Compliance.
AB  - An interim analysis of patient compliance is reported in 234 hypertension
      outpatients who were entered into a large-scale, open, crossover, comparative
      study between a new-generation calcium antagonist, amlodipine (5 mg, once daily),
      and nifedipine SR (20 mg, twice daily). An analysis was also performed on 84
      outpatients with stable angina pectoris, who were included in an open, parallel
      study and received the same dosing regimen of either amlodipine or nifedipine SR
      as the patients in the hypertension arm of the study. In the hypertensive
      patients, there were significant differences in favor of amlodipine, using all
      four methods to assess patient compliance. In the angina patients, a significant
      difference between the groups in favor of amlodipine was only found using the
      "correct dosing" and the "timing compliance" methods. With the traditional pill
      counting and also the "taking compliance" methods, there was no observed
      difference in compliance between the two groups. It was concluded that, in terms
      of patient compliance, once-daily amlodipine was markedly superior to twice-daily
      nifedipine in the crossover study involving the hypertension patients. Amlodipine
      was also better tolerated than nifedipine. In the angina arm of the study,
      patient compliance was again better with amlodipine than with nifedipine, but
      there was no difference observed in the levels of tolerance between the two
      therapies.

PMID- 9156956
TI  - A double-blind evaluation of amlodipine in patients with chronic, stable angina:
      sustained efficacy and lack of "withdrawal phenomenon" upon abrupt
      discontinuation.
AB  - To date, the clinical utility of first-generation, shortacting calcium
      antagonists has not been optimal due to their multiple dosing requirements. This
      has led to poor compliance in some patients. In this study, the safety and
      efficacy of a new generation dihydropyridine calcium antagonist, amlodipine (5-10
      mg once daily) were evaluated in patients with chronic, stable angina pectoris.
      Amlodipine monotherapy was given to 226 patients over an 8-week, single-blind
      period, and the responders (> or = 7% improvement in exercise time) then
      underwent a randomized, placebo-controlled, double-blind withdrawal phase,
      lasting for a further 4 weeks. Amlodipine was shown to be both effective and well
      tolerated in patients with chronic, stable angina pectoris. There was no evidence
      for the development of tolerance to amlodipine over a total of 3 months and there
      did not appear to be any significant problems (of the type noted with abrupt beta
      blocker cessation) associated with its withdrawal.

PMID- 9156957
TI  - Amlodipine: an overview of its pharmacodynamic and pharmacokinetic properties.
AB  - Amlodipine, a third-generation dihydropyridine calcium antagonist, has a mode of
      action and pharmacodynamic profile which are comparable to those of conventional
      compounds in this series, such as nifedipine. Its physicochemical behavior,
      however, appears to be somewhat different. A pKa value of 8.7 means that
      amlodipine is predominantly present in the ionized form at a physiologic pH. It
      possesses, therefore, a strong affinity for cell membranes. These phenomena
      apparently contribute to amlodipine's unique pharmacokinetic profile, which is
      characterized by almost complete absorption, late-peak plasma concentrations,
      high bioavailability, and slow hepatic biodegradation. This profile translates
      into potential clinical benefits by virtue of a slow onset of action and long
      duration of effect. The slow onset of action may explain why there seems to be
      very little reflex tachycardia and a lower incidence of vasodilator side effects
      when comparing amlodipine with conventional dihydropyridines. The slow
      elimination of amlodipine explains the long duration of action, which allows a
      convenient once-daily dosage schedule.

PMID- 9156958
TI  - Amlodipine--does the effect-time profile directly reflect the concentration-time
      profile throughout a 24-hour period?
AB  - Two studies were undertaken to investigate correlations between the time profile
      of plasma drug concentration and the time profile of hypotensive activity for the
      dihydropyridine calcium antagonist, amlodipine. The first study compared the
      concentration- and effect-time profiles for amlodipine and felodipine ER
      (extended release), and the second study characterized the concentration-effect
      relationship in hypertensive patients. The inter- and intra-subject variabilities
      in the disposition characteristics of amlodipine were less than for felodipine
      and there was correspondingly less variability in plasma drug concentrations;
      trough-to-peak ratios were calculated as 67 +/- 8% for amlodipine and 36 +/- 13%
      for felodipine ER. The characteristics of the plasma-concentration profiles
      appeared to be reflected in the profiles of hypotensive response such that,
      although the peak effect with felodipine ER was greater, there was less
      variability with amlodipine and the trough effect with amlodipine was
      consistently superior. Examination of the relationship between the plasma
      concentrations of amlodipine and the antihypertensive effect revealed that,
      although there was a temporal discrepancy between the two profiles, the two could
      be correlated using a linear-effect model. Results of this analysis indicated
      that the kinetic-dynamic model was most appropriately fitted simultaneously to
      the acute and steady-state data. Thus, the low inter- and intra-subject
      variabilities in the disposition characteristics of amlodipine are translated
      into a consistent and smoothly sustained 24-h antihypertensive response.

PMID- 9156959
TI  - Haemodynamic changes during vasodepressor syncope in children and autonomic
      function.
AB  - We investigated postural haemodynamic changes in 24 boys and 30 girls, aged 8-16
      years, with orthostatic intolerance. During the orthostatic test, nine boys and
      seven girls (30%) developed a vasodepressor attack (orthostatic-positive group).
      The orthostatic-positive group had a more marked increase in heart rate (HR) with
      slightly lower systolic blood pressure than the orthostatic-negative group during
      standing, with no significant difference in cardiac output (CO). The shift of
      blood volume from the intrathoracic region to the lower part of the body
      determined by electrical impedance and plasma catecholamines on rising were
      identical in the two groups. At the onset of the vasodepressor attack, CO did not
      change significantly, indicating that sudden arterial vasodilatation was the
      cause. In a pharmacological study on autonomic function, higher sensitivity of
      alpha-adrenoceptor in the resistance vessels was found in the orthostatic
      positive group, but there was no significant difference in the basal level of
      cardiac vagal and sympathetic activity and in cardiac beta-adrenoceptor
      sensitivity between the two groups. The stepwise regression analysis showed that
      the magnitude of HR increment during standing was the most useful indicator in
      predicting the occurrence of a vasodepressor attack. These results suggest that
      low sympathetic activity in the resistance vessels together with an exaggerated
      rise in HR during upright posture is strongly associated with vasovagal and
      vasodepressor attacks in children.

PMID- 9156960
TI  - Effects of low-dose transdermal scopolamine on autonomic cardiovascular control
      in healthy young subjects.
AB  - We studied how posture influences the effects of transdermal scopolamine on
      autonomic cardiovascular regulation in a randomized, double-blind, placebo
      controlled crossover study of 10 healthy young volunteers. We recorded the
      electrocardiogram and auscultatory sphygmomanometric and continuous non-invasive
      finger arterial pressure (Finapres device) to obtain signals for the beat-by-beat
      R-R interval and systolic, mean and diastolic pressures. R-R interval and
      arterial pressure variabilities were characterized by power spectral analysis.
      Scopolamine increased the mean R-R intervals and reduced arterial pressure in
      both the supine and the standing positions, but did not affect blood pressure
      variability. Scopolamine increased the total variability of R-R interval and its
      mid- (0.07-0.15 Hz) and high- (0.15-0.40 Hz) frequency band power in the standing
      position during controlled breathing at 0.25 Hz. In the supine position,
      scopolamine did not affect R-R interval variability. In the deep breathing test,
      scopolamine increased the maximal expiratory-inspiratory R-R interval ratio. This
      study showed that low-dose scopolamine increases vagal cardiac inhibition in both
      supine and standing positions in healthy volunteers. However, scopolamine
      increases heart rate variability only in the standing position during partial
      vagal withdrawal. The study also demonstrates that transdermal scopolamine
      decreases blood pressure in healthy young subjects.

PMID- 9156961
TI  - Differences in lung function and chest dimensions in school-age girls and boys.
AB  - The present analysis was undertaken to find out whether differences in the
      performance of the lungs of boys and girls of the same height are explicable by
      differences in thoracic size. We measured forced vital capacity (FVC), peak
      expiratory flow (PEF) and forced expiratory flows (FEFs), when 50% and 75% of FVC
      had been exhaled (FEF50, FEF75), and standing height, chest width and depth and
      biacromial diameter in 1187 schoolchildren aged 6-18 years. Thoracic dimensions
      were usually greater in boys than in girls of the same height, except for the
      height range of 150.0-164.9 cm. For this height range, the pulmonary function
      variables (PEF, FEF50, FEF75 and PEF/FVC) were significantly higher in girls, and
      for FVC almost as high as the male values. For FEF50/FVC and FEF75/FVC, the
      female values were larger over the whole height range (115.0-184.9 cm), but even
      for these parameters the differences were greatest for the height range 150.0
      164.9 cm. In conclusion, very similar growth patterns of lung function and
      thoracic parameters can suggest that differences in the lung function parameters
      of boys and girls of the same height may be explained by differences in the
      thorax size.

PMID- 9156962
TI  - Artery blood pressure oscillation after active standing up: an indicator of
      sympathetic function in diabetic patients.
AB  - Dynamic artery blood pressure (Finapres) response to active standing up, normally
      consisting of initial rise, fall and recovery above the baseline (overshoot), was
      compared with the early steady-state artery blood pressure level to measure
      sympathetic vasomotor function in healthy subjects (n = 23, age 35 +/- 9 years;
      mean +/-SD) and in type I diabetic patients without autonomic neuropathy (AN)
      (group 1: n = 18, 38 +/- 13 years), with AN but no cardiovascular drugs (group
      2a: n = 7, 44 +/- 11 years) and with both AN and cardiovascular drugs (group 2b:
      n = 10, 47 +/- 7 years). Systolic and diastolic overshoot were similar in the
      control (15 +/- 13/15 +/- 11 mmHg) and group 1 subjects. Systolic overshoot
      disappeared in 57% of patients in group 2a (-1 +/- 9 mmHg; P < 0.03), whereas
      artery blood pressure still overshot in diastole (8 +/- 7 mmHg; NS). Systolic
      overshoot disappeared in all patients in group 2b (-22 +/- 22 mmHg; P < 0.0006)
      and diastolic overshoot disappeared in 60% of these patients (-6 +/- 16 mmHg; P =
      0.0006). Systolic early steady-state level was not lower in group 2a than in
      group 1 (NS), but it was impaired in group 2b (P < 0.006), in which six diabetic
      patients had a pathological response beyond the age-related reference values.
      There was a strong association between the overshoot and steady-state levels (P
      for chi 2 < 0.001, n = 58). Overshoot of the control subjects and patients in
      group 2b correlated to their respective steady-state blood pressure levels (r >
      or = 0.76; P < or = 0.001). In conclusion, baroreceptor reflex-dependent
      overshoot of the artery blood pressure after active standing up diminishes with
      the development of AN and it is associated with the early steady-state level of
      the artery blood pressure.

PMID- 9156963
TI  - Validation of the acetylene rebreathing method for measurement of cardiac output
      at rest and during high-intensity exercise.
AB  - The use of the acetylene rebreathing method to estimate cardiac output (CO)
      during high-intensity exercise, which may be influenced by recirculation of
      acetylene, has not been validated. This study was designed to validate the
      acetylene rebreathing method to measure CO during high-intensity exercise using
      the direct Fick method. CO was measured at rest and during exercise at 25%, 50%,
      75% and 90% of the nine subjects' maximum oxygen uptake (VO2max) by the direct
      Fick and acetylene rebreathing method. CO measured by the acetylene rebreathing
      method correlated with work rate (r = 0.90, P < 0.01) and with oxygen uptake (r =
      0.94, P < 0.01). The correlation coefficient of CO between both methods was r =
      0.91 (P < 0.01). There was no significant difference in CO measured by each
      method at rest as well as at each work rate. The difference in CO between each
      method was greater at lower CO than at higher CO. At 90% of VO2max, the CO
      measured by acetylene rebreathing was nearly identical to that measured by the
      Fick method. It can be concluded that acetylene rebreathing for measurement of CO
      is valid not only at rest but also during exercise, especially during high
      intensity exercise.

PMID- 9156964
TI  - Pulmonary clearance of [99mTc]DTPA and [99mTc]albumin in smokers.
AB  - We measured the pulmonary clearance of [99mTc]DTPA and [99mTc]albumin for 3 h in
      10 non-smokers and 10 healthy smokers. Seven of the non-smokers had a
      monoexponential clearance of [99mTc]DTPA with a mean half-life of 66 +/- 18 min.
      The other three had a biexponential clearance of [99mTc]DTPA with a fraction of
      radio-activity clearing rapidly (fF) of 14 +/- 4%. Eight smokers had
      biexponential clearance of [99mTc]DTPA. The half-life of the fast and slow
      clearance components was 12 +/- 5 and 62 +/- 11 min respectively. The fF was 56
      +/- 25%. Two of the smokers showed a monoexponential clearance of [99mTc]DTPA
      with a half-life of 72 and 55 min. All non-smokers had monoexponential clearance
      curves for [99mTc]albumin, compared with seven smokers. The half-life was 279 +/-
      43 min in non-smokers and 236 +/- 64 min in smokers. The difference in half-life
      was not significant. In three smokers, the clearance curves of [99mTc]albumin
      were significantly better described by a bi-exponential equation. The fF was 22
      +/- 9%. The effects of smoking on the clearance of [99mTc] albumin appear to be
      qualitatively similar to those on the clearance of [99mTc]DTPA. Clearance of
      [99mTc]albumin seems less sensitive to the effects of smoking than clearance of
      [99mTc]DTPA.

PMID- 9156965
TI  - The non-invasive acetylene rebreathing method for estimation of cardiac output:
      influence of breath-by-breath variation.
AB  - The inert gas rebreathing method enables non-invasive estimation of pulmonary
      capillary blood flow, lung tissue volume, transfer factor and functional residual
      capacity. In the present study, we have examined the influence of breathing
      pattern during the rebreathing manoeuvre on the precision of the rebreathing
      method, both theoretically and experimentally. We examined whether the precision
      of the method could be improved by the guidance and training of the subjects
      doing the rebreathing manoeuvre. The results of the theoretical study showed that
      the precision and accuracy of the rebreathing method are practically insensitive
      to random variation in the breathing pattern. Simulated breath-by-breath
      variations up to +/-50% of the average 3.01 VT resulted in coefficients of
      variation of about 3% for QC and about 5% for VTC. Simulated breath-by-breath
      variations indicate that with mean tidal volume or rebreathing bag volume lower
      than 1.01 the precision will worsen, and with tidal volume lower than 1.5 1 the
      accuracy will worsen. The experimental results showed no significant improvement
      in the precision of the rebreathing method by visual guiding and training of the
      subjects to optimize the breathing pattern during the rebreathing manoeuvre.

PMID- 9156966
TI  - Haematocrit, plasma volume and noradrenaline in humans during simulated
      weightlessness for 42 days.
AB  - Previous results from our laboratory demonstrate that changes in haematocrit
      (Hct) and haemoglobin concentration (Hb) underestimate the relative (%) change in
      plasma volume (PV) in seated subjects during simulation of weightlessness by
      water immersion. Therefore, we examined whether changes in Hct and Hb would
      accurately reflect the changes in PV in seven subjects during simulation of
      weightlessness by another model, 6 degrees head-down tilted bed rest (HDBR), for
      42 days. Since we have previously observed unexpectedly high plasma levels of
      noradrenaline (NA) in astronauts during space flight, we also took the
      opportunity to measure this variable. The measurements were compared with those
      of the supine horizontal position before and after HDBR. During HDBR, PV measured
      by the Evans blue dye dilution technique decreased by 6.1 +/- 2.8% (P < 0.05) on
      day 2 and 9.6 +/- 2.2% (P < 0.05) on the 42nd day compared with that of the
      supine, horizontal position. Based on changes in Hct and Hb, PV decreased
      similarly by 8.3 +/- 2.8 and 10.2 +/- 3.2% (P < 0.05) respectively. There were no
      differences comparing the results of the two methods (P > 0.05). Forearm venous
      plasma NA was unchanged during the whole course of HDBR compared with that of the
      pre-HDBR supine position. It is concluded that changes in Hct and Hb reliably
      reflect the changes in PV comparing prolonged HDBR with the pre- and post-HDBR
      horizontal, supine position. Thus, changes in Hct and Hb might accurately reflect
      the change in PV during weightlessness in humans provided that the horizontal
      supine position is used as the ground-based reference. Furthermore, the results
      of this study, as well as of previous studies from space, confirm that NA release
      is unchanged or even increased during weightlessness.

PMID- 9156967
TI  - Psychological characteristics of dissatisfied denture patients.
AB  - A field study was conducted to investigate the psychological characteristics of
      dissatisfied denture patients using validated personality inventories. In the
      present study dissatisfied denture patients are patients that keep complaining
      about their dentures and are referred to a psychologist because it was suspected
      that their complaints may also be due to psychological factors. The results show
      that these patients feel more inhibited in their social contacts and more often
      have the opinion that wearing dentures is unacceptable. Also these patients are
      high on neuroticism, less social adequate, more rigid, have less self-esteem and
      are more externally oriented.

PMID- 9156968
TI  - Heterochromatin (chromosome dots and chromocentres): key to planarian
      regeneration?
AB  - Regenerating planaria were treated with colchicine dissolved in planarian saline
      solution in order to harvest metaphase chromosomes. Slides containing such
      chromosomes were incubated in phosphate buffer at high temperature for 2h and
      stained with Giemsa solution in order to view heterochromatic dots in
      chromosomes. The chromosomes were found to contain massive regions of dense
      heterochromatin. In addition, most interphase cells exhibited numerous densely
      staining chromocentres. Heterochromatin has been postulated to reduce the
      duration and enhance the speed of the cell cycle, and previous work has
      implicated heterochromatin in cells undergoing rapid division. These findings
      imply that the profound regenerative potential of planarians may be due to their
      high cellular levels of heterochromatin.

PMID- 9156969
TI  - Gag reflex and dysphagia.

PMID- 9156970
TI  - 5th Annual meeting of the Dysphagia Research Society. Aspen, Colorado, October 31
      November 2, 1996. Abstracts.

PMID- 9156971
TI  - [Perioperative hygiene in trauma surgery].

PMID- 9156972
TI  - [Report of experiences of 3 years' use of rectal endosonography in a surgical
      department of basic and routine care].

PMID- 9156973
TI  - [Pending EBM becomes effective 1 July 1997].

PMID- 9156974
TI  - [Prevention of thrombosis with the walking cast--patient education regarding
      risks and treatment alternatives. Decision of the federal court 21 November 1995-
      VI ZR 329/94].

PMID- 9156975
TI  - [Classification of neuroendocrine tumors of the gastrointestinal tract and
      pancreas and its therapeutic relevance].
AB  - In this review therapeutic strategies for neuroendocrine tumors of the
      gastrointestinal tract and the pancreas are proposed, based on the recent
      classification. Generally, for all neuroendocrine tumors even with obvious
      metastases, surgery is recommended. Particularly for neuroendocrine tumors of the
      upper intestinal tract and the pancreas as extensive preoperative clinical and
      histopathological diagnosis is required. We tried to simplify the therapeutic
      strategies according to the classification; in several cases, however, very close
      cooperation between gastroenterologists, surgeons and pathologists is necessary
      to decide on the appropriate therapeutic strategy.

PMID- 9156976
TI  - [Special diagnostic and therapeutic aspects of insulinoma].
AB  - Insulinomas are rare tumors and account for 90% of all endocrine pancreatic
      tumors. They typically present as a solitary tumor, but may occur in multiple
      sites (e.g. multiple endocrine neoplasia type I) or as a malignant disease in 10%
      of cases and rarely as nesidioblastosis or islet cell adenomatosis.
      Neuroglucopenic symptoms lead to the diagnosis; inadequate high insulin and C
      peptide secretion with hypoglycemia in the fasting test confirm the diagnosis.
      Preoperative localization is not necessary prior to the first operation. The
      standard operation is enucleation, or depending on size and location, resection.
      The treatment of multiple tumors and islet cell hyperplasia with a high risk of
      recurrence is problematic. Subtotal resection plus enucleation seems to be better
      than selective tumor resection. In malignant insulinomas, mostly presenting with
      liver metastases, aggressive surgical therapy with hepatectomy and debulking,
      chemoembolization and systemic chemotherapy are the modalities of choice.

PMID- 9156977
TI  - [Diagnosis and therapy of liver metastases of neuroendocrine tumors].
AB  - Neuroendocrine tumors are rare and slowly progressing malignancies developing
      predominantly in the gastrointestinal tract. Often symptoms caused by excessive
      hormone production lead to diagnosis, especially when active metabolites are
      released from hepatic metastases to reach the systemic circulation before they
      are inactivated in the liver. Preoperative diagnosis of specific tumors relies on
      demonstration of the respective hormones in serum or urine than on histological
      diagnosis. Localization of primaries or their metastases can be accomplished by
      CT-AP, somatostatin receptor scintigraphy, SPECT or PET studies with high
      sensitivity. At the time of diagnosis more than 60% of tumors have already spread
      to the liver. Potentially curative resection of liver metastases can achieve 5
      year survival rates of more than 60%. Since excess hormone production may be
      incapacitating and even life-threatening, effective palliation is highly
      important. Five-year survival following palliative liver resection was calculated
      to be the almost 40%. Palliative liver resection may therefore be considered an
      alternative to liver transplantation with 5-year survival of 34% in a collected
      series. If liver resection is not possible, at least temporary palliation of
      symptoms and retardation of tumor growth can effectively be achieved with
      somatostatin analogues.

PMID- 9156978
TI  - [Carcinoid tumor--a questionable entity?].

PMID- 9156979
TI  - [Surgical therapy of neuroendocrine tumors of the thymus].
AB  - Neuroendocrine tumors of the thymus, also known as thymic carcinoids, are rare
      tumors of the anterior mediastinum. They occur sporadically or in association
      with MEN I syndrome. We present five patients (four male, one female; age of
      first manifestation 19-53 years) who were operated on at our hospital between
      1984 and 1995 for neuroendocrine thymic tumors. A hormone-producing tumor
      presented with Cushing's syndrome in two patients. Two patients had MEN I
      syndrome. Only in the female patient the primary tumor was confined to the
      thymus. We found lymph node metastases in three patients and a distant metastasis
      in one. The neuroendocrine tumors have a high rate of local recurrences and thus
      we performed 11 operations using a transthoracic or transsternal approach. Since
      there was no operative mortality and adjuvant therapies are of limited value, we
      recommend surgery even in case of recurrence.

PMID- 9156980
TI  - [Outcome of surgical therapy in asymptomatic primary hyperparathyroidism].
AB  - Surgery for symptomatic hyperparathyroidism remains the standard therapy.
      Asymptomatic primary hyperparathyroidism (pHPT) is being diagnosed with
      increasing frequency owing to broad serum testing. Indications for surgery in
      this setting are controversial. For evaluation of surgical safety we performed a
      retrospective analysis of our patients who were being operated on for
      asymptomatic pHPT. From January 1988 until August 1995, 243 patients were treated
      for pHPT and registered prospectively at our unit. Seventy-six patients were
      classified as asymptomatic. In all, 75% of the patients were female; the mean age
      was 62 years. In this group, 87% of the patients had cervical sonography in order
      to localize the adenoma. Highly selective venous catheterization was required in
      cervical reexplorations. Statistical analysis for potential prognostic factors
      for the clinical outcome was performed. Successful cervical exploration was
      possible in 71 patients (94.7%). With 4 patients remaining hypercalcemic, the
      rate of persistency was 5.2%. Localization procedures were correct in 58% for
      cervical ultrasound and 77% for selective venous catheterization. Postoperative
      morbidity included one permanent recurrent laryngeal nerve palsy and 2 patients
      with hemorrhage who were treated by reoperation. While one case of permanent
      hypoparathyroidism was well controlled by oral supplementation, 18 patients
      recovered from temporary hypoparathyroidism. No postoperative mortality occurred.
      Risk factor analysis revealed only cervical reexplorations for HPT to be
      associated with a higher morbidity (P = 0.02). Surgery for asymptomatic pHPT can
      be performed with reasonable safety. Cervical reexplorations in asymptomatic
      patients should be reserved for special indications. Apart from this small group,
      all patients should be evaluated for surgery.

PMID- 9156981
TI  - [Prospective observational study of surgical therapy of renal
      hyperparathyroidism].
AB  - A prospective long-term follow-up study in patients who had had surgical therapy
      for renal hyperparathyroidism was launched to investigate the results of surgical
      treatment and to evaluate possible correlations between preoperative laboratory
      values and the course of symptoms. From August 1987 to December 1995, 79 patients
      underwent surgery for renal hyperparathyroidism. It was the first neck
      exploration for 72 patients. Total parathyroidectomy with autotransplantation to
      a forearm was our preferred procedure (n = 67). The postoperative course of all
      patients is know. We carried out one to nine reexaminations (median 4) in 74 of
      79 patients. The follow-up period ranged from 1 month to 5 years with a median of
      18 months. After the operation transient hypocalcaemia occurred in 84.4% of
      patients. Postoperative hypocalcaemia correlated negatively with the preoperative
      levels of alkaline phosphatase and intact parathyroid hormone. Within the first
      month after surgery 60% of the preoperatively affected patients completely
      recovered from pruritus, whereas the skeletal syndrome took longer to disappear.
      One year after surgery 75% of the patients with pruritus and 79% of those with
      skeletal syndrome had became asymptomatic. After total parathyroidectomy with
      autotransplantation, patients with preoperatively elevated concentrations of
      alkaline phosphatase (> 200 U/I) experienced faster relief from joint pain than
      patients with preoperatively normal concentrations (P = 0.0297). To date 4.5% of
      the patients developed recurrent hyperparathyroidism after total
      parathyroidectomy with autotransplantation. Morbidity of surgery for renal
      hyperparathyroidism is influenced by patients' risk factors. Postoperative
      hypocalcaemia correlates negatively with the grade of renal osteopathy at the
      time of operation. Preoperative concentrations of alkaline phosphatase influence
      the rapidity of the relief from joint pain.

PMID- 9156982
TI  - [Results of endoscopic, retroperitoneal adrenalectomy with special reference to
      the intraoperative course].
AB  - In 20 patients the hemodynamic and ventilatory data during endoscopic
      retroperitoneal adrenalectomy were checked retrospectively to analyze the
      hemodynamic and ventilatory effects of a pneumoretroperitoneum. After
      insufflation of CO2 into the retroperitoneal space we observed an increase in
      systolic blood pressure [median 180 mm Hg ([130-200)]. Analyzing the ventilatory
      parameters we noted that the minute ventilation had to be increased by a median
      value of 4.25 I (0.4-13) to reduce the increased carbon dioxide levels during CO2
      insufflation. After insufflation of CO2 into the retroperitoneal space we
      observed no major complications. We therefore believe that retroperitoneal
      endoscopic adrenalectomy is also indicated in patients with cardiac or pulmonary
      diseases.

PMID- 9156983
TI  - [Intra-abdominal schwannoma. Diagnosis and surgical therapy].
AB  - We report three patients who were operated on because of an intraabdominal
      schwannoma between February 1991 and October 1994 in our department. In the first
      case, a benign gastric schwannoma was treated by a distal gastric resection
      (Billroth II); the main symptom was gastric bleeding. In the second case, a
      malignant duodenal schwannoma with liver metastasis was treated by wide en-bloc
      resection of the tumor including retroperitoneal lymphadenectomy and an
      anatomical resection of the right lobe of the liver. A metachronous metastasis of
      the liver, appearing 7 months postoperatively, was treated by intraparenchymatous
      laser coagulation; a local recurrence, appearing 19 months postoperatively, led
      to another tumor resection. The main symptom was a palpable intraabdominal mass
      in this case. In the third case, a malignant schwannoma of the abdominal wall was
      resected in fragments in another clinic. Six months later a local recurrence with
      infiltration of the liver appeared in spite of postoperative radiation and was
      resected en bloc. Early peritoneal sarcomatosis was apparent at that time.
      Postoperative chemotherapy did not prevent quick progression of the tumor. The
      patient died 18 months after the first operation. The clinical presentation,
      differential diagnosis and operative strategy for benign and malignant
      intraabdominal schwannomas are discussed.

PMID- 9156984
TI  - [Venous angiomatous hamartoma of the mesenteric root. Therapy of chylous ascites
      abd chylothorax--case report].
AB  - Hamartomas are rare benign tumors appearing very often without any symptoms. In
      case of diagnostic detection the operative exploration is indicated for a correct
      histological diagnosis and resection. In this report we describe a very rare case
      of mesenterial hamartoma. During the late postoperative course a refilling
      chylothorax and chylous ascites occurred. With total parenteral nutrition,
      excluding short- and long-chain fatty acids, chylous leakage was successfully
      treated. The chylous exudation was stopped totally; only intraabdominally did
      minimal ascites persist. The therapy was continued by a oral Ceres diet
      nutrition. The conservative therapy involving total parenteral nutrition
      permitted us to avoid the peritoneovenous Le Veen shunt and the associated
      complications.

PMID- 9156985
TI  - [Late results of surgical treatment of acute and chronic instability of the ulnar
      collateral ligaments].
AB  - A total of 113 patients with acute and chronic instability of the ulnar
      collateral ligament metacarpal phalangeal (MP) joint of the thumb were treated
      surgically between 1980 and 1985; 82 patients were followed up after a mean
      period of 10 years. Of 59 patients with acute injuries, 52 were painfree with
      full stability of the MP joint; 23 patients with chronic instability and tendon
      grafting also showed restoration of stability. Nevertheless, the range of motion
      was reduced severely and opposition of the thumb was impaired. The results of
      follow-up reveal that acute reattachment of the injured ulnar collateral ligament
      is more effective.

PMID- 9156986
TI  - [Duodenum preserving resection of the head of the pancrease in therapy of
      pancreas divisum].
AB  - In 1-6% of the patients who are investigated by endoscopic retrograde cholangio
      pancreatography a pancreas divisum can be found. In some patients pancreas
      divisum can lead to an acute relapsing and finally chronic pancreatitis (CP).
      Surgical intervention in these cases seems to offer a good chance of recovery. We
      report our experience with the duodenum-preserving resection of the head of the
      pancreas in 12 patients with pancreas divisum and CP. In all patients the
      preoperative evaluation showed clinical, functional or radiological signs of CP.
      The duodenum-preserving resection of the head of the pancreas was carried out in
      all patients without perioperative mortality. Ten postoperative versus eight
      preoperative patients showed a pathological exocrine function of the pancreas.
      Endocrine function, measured by the oral glucose tolerance test (OGTT), improved
      postoperatively in two patients. Eleven patients who were investigated after a
      mean follow-up time of 31 months (3-75 months) were completely pain free. No late
      mortality occurred. OGTT revealed a diabetic endocrine function in two patients.
      Disturbed exocrine pancreatic function had to be substituted in nine patients.
      One patient had to be reoperated by duct incision and renewal of the pancreatico
      jejunostomy 10 months after the first operation. In conclusion, the duodenum
      preserving resection of the head of the pancreas reduced pain in all patients
      with pancreas divisum and CP and may lead to an improvement of endocrine
      pancreatic function. Other, nonresecting procedures or endoscopic interventional
      therapy should be avoided in these patients.

PMID- 9156987
TI  - [Traumatically-induced closure with spontaneous recanalization of the internal
      carotid artery].

PMID- 9156988
TI  - [Intestinal hamartomatous venous hemangioma in childhood].
AB  - Hemangiomas of the gastrointestinal tract are very rare in both children and
      adults. The following case history describes a child with uncharacteristic
      abdominal pain and stenosis of the terminal ileum. Intraoperatively we found an
      enlarged hamartomatous alteration of the ileocecal region. The histological
      analysis showed a hamartomatous venous hemangioma. Problems concerning
      classification and diagnosis are discussed.

PMID- 9156989
TI  - [Transtracheal monitoring of the recurrent laryngeal nerve. Prototype of a new
      tube].
AB  - A new sensing device for the continuous intraoperative monitoring of the
      recurrent laryngeal nerve is presented. It is based on a double ballooned
      endotracheal tube including stimulating and tracing electrodes. The system is
      characterised by three advantages: 1) it is atraumatic, 2) it is operating
      completely outside the operating field (extraterritorially), 3) nerve function is
      being monitored continuously from the time of intubation to the time of
      extubation. The presented system has been evaluated in piglets. First results in
      humans will be available shortly.

PMID- 9156990
TI  - [Hans von Haberer--the beginnings of reconstructive carotid surgery].
AB  - Hans von Haberer (1875-1958) gained wide experience in the reconstructive surgery
      of vascular aneurysms at the universities of Innsbruck, Graz, Dusseldorf and
      Cologne. In this period he operated on 421 vascular aneurysms--including 30
      carotid aneurysms--mainly by means of direct circular vascular suture. In 1914
      von Haberer described the first repair of a carotid aneurysm. Therefore he is the
      pioneer of reconstructive carotid surgery. Based on detailed clinical and
      operation reports on approximately 16,000 cases, written by Hans von Haberer
      between 1904 and 1949, and on the contemporary literature, we describe his
      experience in vascular surgery.

PMID- 9156991
TI  - [Laparoscopic adrenal gland surgery].
AB  - Minimally invasive adrenalectomy is now an accepted alternative to conventional
      adrenalectomy. As in open surgery, several different endoscopic approaches to the
      adrenal glands have been described. In principle, one must distinguish between
      the laparoscopic and the retroperitoneoscopic access. All adrenal tumors-
      pheochromocytomas included--except adrenal carcinomas can be removed
      endoscopically. However, the use of these techniques is limited in patients with
      particularly large tumors. The results reported to date are convincing. Only
      limited data are available as yet to compare conventional and endoscopic
      adrenalectomy. Because adrenal diseases requiring surgery are rare, endoscopic
      adrenalectomy is an operation that, for the present, will be limited to centers
      with a particular interest in laparoscopic and endocrine surgery.

PMID- 9156992
TI  - [Suffering and misfortune--the beginning of comprehension].
AB  - Pain, suffering and damage are important items of the animal protection law and
      thus the basis for its accomplishment. It is the aim of this paper to give a
      review on those methods which are available to record and to assess well-being or
      suffering of animals. Since suffering cannot be measured directly different
      indicators such as health, productivity, physiological and biochemical parameters
      and behaviour have to be used in order to obtain conclusive evidence of suffering
      or well-being. Since it has to be taken into account that the individual
      indicators are of limited value with respect to their reliability and accuracy
      the combination of these indicators has to be recommended.

PMID- 9156993
TI  - [Pain conditioned changes in animal behavior].
AB  - Other than in human beings, only nonverbal methods including motor reflexes,
      autonomic reflexes, neuroendocrine responses, and changes in overall behavior are
      available for pain evaluation in various animal species. Pain-like changes in
      most of these variables can be induced by approaching and handling conscious
      animals rendering increases in heart rate, blood pressure, and plasma
      catecholamine levels, etc. to nonspecific indicators for pain. In recent years,
      changes in overall behavior have been used for assessment of animal pain.
      Multiple Pain Discomfort Scales (MPDS) have been established for objective
      evaluation of behavioral changes in response to both noxious stimulation and
      analgesic drug therapy. These Multiple Pain Discomfort Scales include species
      specific behavioral patterns, making this approach a potentially more specific
      indicator of animal pain. This, however, needs to be confirmed by further
      extended studies in the near future.

PMID- 9156994
TI  - [The problem of free living urban pigeons].
AB  - The biology and behaviour of urban pigeons is presented in this article. When
      changes in the population density of pigeons by capture, shooting, or
      intoxication are intended, the breeding behaviour has to be considered. A
      constant reduction of pigeons according to the law for the prevention of cruelty
      against animals can only be achieved by a restricted feeding if feeding at all.

PMID- 9156995
TI  - [Sociocultural reasons for the pigeon problem].
AB  - The feeding of animals as a friendly gesture is deeply rooted in man. This
      behaviour has a negative effect on the Street-pigeons which as a consequence
      suffer from overpopulation. The problem can only be solved by limiting this
      feeding. The pigeon-feeders are the cause of the pigeon-problem in our cities.
      The feeders can by their motivation be classified in various groups. Play-feeders
      and display-feeders can be recognised. They are more easily to be dealt with than
      the fanatical pigeon-friends who show a strong emotional attachment to these
      birds. The pigeon-problem can be overcome if this stubborn group can be taught to
      change his behaviour. Such a solution would be highly rewarding as great sums of
      money are spent to remove damages caused by the pigeons to buildings and works of
      art.

PMID- 9156996
TI  - [Legal principles in criminal and regulatory infringements-- proceedings of the
      view of the public prosecutor].
AB  - In legal proceedings referring to animal welfare, an effective collaboration
      between Veterinary officials, public prosecutor and police authorities is of
      eminent significance. Intensive communication among all authorities involved
      helps to solve the relevant facts and thus leads to a just ruling. Only by this
      way an effective prosecution of infringements and criminal proceedings will be
      ensured.

PMID- 9156997
TI  - [Investigation, securing of evidence and judgment in violations of animal welfare
      regulations].
AB  - For successful implementation of proceedings against violation of animal welfare
      regulations, sound investigation, securing of evidence, and assessment of the
      facts is essential. Recommendations are given to carry through as well as hints
      for drafting the reports required.

PMID- 9156998
TI  - [Adequate animal housing and existence regulations of cats].
AB  - Behavioural problems and the number of sick animals are amongst the most valuable
      criteria for evaluation of adequate housing conditions in cats, especially for
      official veterinarians, and can provide help for expert opinions. Good animal
      keeping involves prophylactic hygienic measures which also reduce the health risk
      for animal owners. Masshousing of cats, is usually not suitable for the
      individual animal and represent a hygienic risk for the pet and the owners.
      Restriction can achieved by prohibition or restriction to qualified persons after
      passing an examination. The regulation of feline populations and the resulting
      problem of feral cats require systematic measures. Fighting the underlying
      reasons, neutering and marking of all cats are the most important factors.
      Catching and neutering feral cats has implications to animal welfare and animal
      hygiene and is therefore dependent on public support and systematic handling by
      the responsible officials.

PMID- 9156999
TI  - [Stress response of slaughter pigs in two different access systems to electrical
      stunning].
AB  - Investigations on two batches of 25 pigs each were carried out to characterize
      two different access systems for electrical stunning by physiological responses
      such as heart frequency (HF) and the blood constituents lactate and cortisol. All
      animals were of the same hybrid breeding program. The access race in system A,
      where the animals are separated was 11 m long. The personnel used different
      equipments including electrical rods to move the pigs forward. The lairage time
      after transport was between 1 to 2 h. In system B the animals arrived the evening
      before slaughter and spent the night in groups in straw-littered lairage boxes.
      The access race was 3.5 m long. The heart frequencies of the pigs in system A
      were between 80 and 240 beats/min, in system B the average HF were between 60 and
      170 beats/min. In the lairage the HF were at about 113 beats/min (system A) and
      66 beats/min (system B). Blood samples were taken immediately after stunning. The
      lactate concentrations differed by 6 mmol/l (8.6 mmol/l in system A, 2.6 mmol/l
      in system B). Cortisol was distinctly higher in the blood of the animals from
      system A (166 ng/ml) compared to system B (126 ng/ml). The results show that the
      used techniques are suitable to examine stress indicators of pigs under practical
      conditions. Access systems with long races seem to pose a higher stress than
      short access ways. The influence of handling (human factor) and management (size
      of groups, origin of pigs) is equally important. The role of longer resting times
      in the lairage should be investigated in more detail. This should also include
      the keeping conditions on the farm where the animals are raised.

PMID- 9157000
TI  - [Pain caused by breeding in dogs].
AB  - According to German animal protection law it is not aloud to breed animals if it
      has to be expected that the offspring will suffer pain caused by hereditary
      characters. This paper deals with those hereditary defects which are used
      directly or indirectly (because of linkage to other desirable traits) in dog
      breeding. By the patho-physiological symptoms and the genetics of selected
      hereditary defects recommendations are exemplified how these defects should be
      handled in breeding that pain can be avoided.

PMID- 9157001
TI  - [Pain caused by breeding: definition, judgment, pathogenesis].
AB  - Special terms of the "German Animal Protection Law (section 11b)"and the
      "European Agreement for Protection of Domestic Animals" particularly "torture
      breeding, genetic characteristics, well-being, soundness, pains, injuries and
      specific use" are commented. Examples of torture-breedings are discussed: Dog
      (Merle-faktor, brachycephalie, atrichosis), cat (Mans-factor, W-gene, folded
      ears), birds (tuffs, ear-drops, tailesness, hypertrophy of bill-warts, abnormal
      position of tarsal-joints, hypertrophy of imposing behavior).

PMID- 9157002
TI  - [Pain in the breeding of fish].
AB  - Excessive breeding leading to suffering in animals only exists in ornamental
      fish, especially in gold fish or poecillids. These varieties are physically
      handicapped in locomotion, feeding and/or reproduction in comparisation to wild
      fish.

PMID- 9157003
TI  - [The Animal Welfare Center of the Veterinary School of Hanover].
AB  - Animal welfare is initiated from different motivations with very different
      targets. The main areas are the emotional, the legal and the scientific animal
      welfare. The intention of a scientifically based animal welfare is discussed. The
      new founded animal welfare center of the veterinary school in Hannover initiates,
      coordinates and promotes research in the direction of a scientific animal welfare
      from the understanding and conviction that only knowledge protects animals.

PMID- 9157004
TI  - [Animal Welfare Service of Lower Saxony--first report of experiences].
AB  - The Animal Welfare Service of Lower Saxony-part of the state veterinary services
      within the regional government of Weser-Ems-started its work in February 1995 at
      Oldenburg. The experiences during the first 18 months of activity are discussed.
      The main duties of the Service consist of: Advising the local district veterinary
      authorities concerning "problem" holdings including common control visits on
      occasion. Advising the offices of the court on matters concerning animal
      protection. Advising government offices and legislative bodies on the development
      and improvement of animal welfare legislation. Working on special problems of
      animal welfare. In particular the Service aided by various working groups is
      currently establishing welfare recommendations for the special fields of turkey
      fattening and all year grazing of cattle and sheep.

PMID- 9157005
TI  - [Effect of hot-air balloon crossings on animals in the open air].
AB  - Since the middle of the eighties owners of animals increasingly claimed
      compensation from balloon pilots. They asserted, that their animals got restless
      due to strange optical and acoustical stimuli caused by low altitude crossing of
      hot-air balloons and were damaged while trying to get out of the way or to
      escape. Very low altitude "Contour crossing" of hot-air balloons, mainly forming
      the basis of complaints, is only left possible in a limited degree in Germany
      since the air traffic regulations were changed to a higher minimum safety
      altitude (Air Traffic Act, LuftVO, version of March 21, 1995) and the violating
      balloon pilot may be disciplined. The paper is dealing with the principle of hot
      air ballooning, with the feasibility of the pilot to avoid and restrict damages,
      with the possibilities to assign damages to a potential cause and with the legal
      basis.

PMID- 9157006
TI  - Exposure of tubulin structural domains in Nicotiana tabacum microtubules probed
      by monoclonal antibodies.
AB  - A panel of nine antibodies, specific to antigenic determinants located on N- or C
      terminal structural domains of alpha and beta subunits of animal tubulin, and
      antibodies against acetylated, tyrosinated and polyglutamylated tubulins were
      utilized for probing the Nicotiana tabacum microtubules. The specificity of
      antibodies was confirmed by immunoblotting on whole cell lysates and on tubulin
      isoforms separated by high-resolution isoelectric focusing. Whereas antibodies TU
      01 and TU-09 reacted with all alpha-tubulin isoforms and TU-06 reacted with all
      beta-tubulin isoforms, the other antibodies reacted with a limited number of
      tubulin isoforms. Antibody TU-14 reacted only with two beta-tubulin charge
      variants. In fixed cells, each of the antibodies stained microtubules of
      preprophase band, mitotic spindle and phragmoplast. Cortical microtubules were
      stained by all antibodies except TU-02 and TU-03, which did not decorate
      microtubules in interphase cells. Immunostaining of unfixed detergent-extracted
      cells revealed that antibodies against determinants on the C-terminal domains of
      both subunits decorated microtubules, but these were not stained with antibodies
      to determinants on the N-terminal domains. These data indicate that in plant
      microtubules at least several parts of the N-terminal domains of both subunits
      are either not exposed on the microtubule surface or are masked by the other
      proteins. In contrast, parts of the C-terminal domains are exposed on the
      exterior of microtubules. As for animal tubulins the majority of
      posttranslational modifications as well as binding sites for microtubule
      associated proteins (MAPs) have been located to these regions, it is possible
      also in higher plants that the C-terminal structural domains of both tubulin
      subunits participate in the modulation of tubulin interactions with associated
      proteins.

PMID- 9157007
TI  - Rearrangements of F-actin arrays in growing cells of intact maize root apex
      tissues: a major developmental switch occurs in the postmitotic transition
      region.
AB  - Immunofluorescence labeling, using a monoclonal antibody developed against actin,
      revealed the relative abundance and rearrangements of F-actin arrays which occur
      in cells of the maize root apex as they make the developmental transition from
      proliferative growth in the meristem to a non-proliferative state in more mature
      root parts, and during the concomitant process of tissue differentiation. Cells
      in both the root cap and the quiescent center are depleted of F-actin, whereas it
      is abundant in cells of the central cylinder but less so in the cortex. The
      cortical cytoplasm associated with the endwalls of both mitotic and postomitotic
      cells is characterized by a more intense reactivity to the actin antibody than
      the longitudinal side walls. A major change in F-actin arrangement occurs in the
      transitional growth region interpolated between the meristem and the zone of
      rapid cell elongation. The location and nature of these F-actin rearrangements
      within the root suggest that the F-actin system might be involved in generating a
      force associated with the developmental transition of cells from their slow near
      isotropic mode of growth close to the base of the meristem, to rapid anisotropic
      growth which is characteristic of the zone of cell elongation. This attraction
      notion was strongly supported using specific inhibitors of F-actin and myosin.

PMID- 9157008
TI  - Heterotypic interactions and filament assembly of type I and type II cytokeratins
      in vitro: viscometry and determinations of relative affinities.
AB  - We have determined relative affinities of type I and type II human non-epidermal
      cytokeratin (CK) polypeptides synthesized in Escherichia coli from cDNA, using
      the method of surface plasmon resonance, and have compared the influence of ionic
      strength and ion quality on the assembly to intermediate filaments (IFs) by
      viscometry and electron microscopy. By surface plasmon resonance (total internal
      reflection) we determined the real-time relative binding of various type I CKs to
      the type II CK8. Surprisingly, the various type I CKs examined (i.e., CKs 13, 18,
      19 and 20) differed markedly in their relative binding rate: For example, CK18
      and CK13 displayed much higher resonance signals than CK19 and CK20. In addition,
      soluble complexes of type II CK8 with various type I cytokeratins were
      reconstituted at slightly alkaline pH and low ionic strength. Subsequent IF
      assembly was induced by simultaneous shifting to neutral pH and increasing the
      ionic strength. Both mono- and divalent ions as well as tris (hydroxymethyl)
      aminomethane (Tris) alone were able to induce IF assembly. When we compared the
      time course of viscosity increase of CK8 in combination with either CK13, CK18,
      CK19 or CK20, we found that the cytokeratin pairs 8:18 and 8:20 attained the
      highest viscosity values, whereas the cytokeratin pair 8:19 displayed a
      relatively low value. Significantly lower values of specific viscosity were also
      observed in competition experiments when CK18 was gradually replaced by CK19. The
      observed differences in relative affinities and assembly kinetics of certain CK
      combinations allow quantitations of the interactions between different CKs and
      are discussed in relation to IF stability and cell differentiation.

PMID- 9157009
TI  - Myogenin expression is necessary for commitment to differentiation and is closely
      related to src tyrosine kinase activity in quail myoblasts transformed with Rous
      sarcoma virus.
AB  - Quail myoblasts transformed with a temperature-sensitive mutant of Rous sarcoma
      virus (QM-RSV cells) proliferate at 35.5 degrees C, a permissive temperature for
      RSV, but differentiate at 41 degrees C, a nonpermissive temperature, with the
      formation of multinucleated myotubes and the synthesis of muscle-specific
      proteins. Tyrosine kinase activity of the src gene product derived from RSV is
      closely related to regulation of this temperature-dependent differentiation, and
      the cells obtain commitment to differentiation by incubation for about 12 h at 41
      degrees C with dephosphorylation of tyrosine-phosphorylated protein(s). It was
      examined how myogenin, a member of myogenic regulatory factors, participates in
      commitment to differentiation and tyrosine dephosphorylation of QM-RSV cells.
      Myogenin was expressed within 8 h and reached a plateau within 10 h at 41 degrees
      C. Each cell clone whose differentiation proceeded faster or slower than the
      parental QM-RSV cells was reflected by a faster or slower myogenin expression,
      corresponding to the time that is required for commitment to differentiation. It
      was suggested that there is a lag time between myogenin expression and the
      acquisition of commitment in QM-RSV cells. On the other hand, at 35.5 degrees C,
      a condition which suppresses differentiation, myogenin expression was not
      detected. However, herbimycin A, an inhibitor of protein tyrosine kinase, induced
      myogenin expression even at 35.5 degrees C. On the contrary, myogenin expression
      was inhibited at 41 degrees C by sodium orthovanadate, an inhibitor of tyrosine
      phosphorylated protein phosphatase. Furthermore, forced induction of myogenin
      into the cells cultured at 35.5 degrees C resulted in the formation of
      multinucleated myotubes and the synthesis of muscle-specific proteins. These
      results suggest that myogenin expression is one of the indispensable conditions
      for the acquisition of commitment to differentiation and is regulated by tyrosine
      phosphorylation and dephosphorylation of some protein(s) in QM-RSV cells.

PMID- 9157010
TI  - Protein kinase C isoforms undergo quantitative variations during rat
      spermatogenesis and are selectively retained at specific spermatozoon sites.
AB  - Signal transduction elements, including protein kinase C, have been identified in
      mammalian spermatozoa. In order to evaluate the pattern of expression and the
      subcellular localization of nine different protein kinase C isoforms in the
      course of spermatogenesis, we utilized quantitative electron microscopy
      immunocytochemistry on thin sections of rat seminiferous tubules. The results
      indicate a progressive reduction of the protein kinase C isoforms present in the
      early stages of spermatogenesis, so that in late spermatids none of them is
      present in the nucleus, while the isoforms alpha, gamma and beta II are
      specifically retained in the acrosome, the isoforms beta I and zeta in the neck,
      and the isoform epsilon in the tail. These isoforms, except for beta II, are
      maintained at the same sites in spermatozoa. Western blotting analysis indicates
      the presence of alpha and gamma isoforms in the head subfraction, and of beta I,
      zeta and epsilon isoforms in the tail subfraction of spermatozoa. These findings
      suggest that specific protein kinase C isoforms may be functionally involved in
      some events of spermatozoa differentiation and, eventually, in the fertilization
      process.

PMID- 9157011
TI  - The calcium-binding protein VILIP in olfactory neurons: regulation of second
      messenger signaling.
AB  - Visinin-like-protein (VILIP), a member of the neuronal subfamily of EF-hand
      calcium-sensor proteins is shown to be expressed in olfactory sensory cells of
      the rat nasal epithelium. Its prominent localization in cilia and dendritic knobs
      the chemosensory compartments of olfactory neurons-suggests that the calcium
      binding protein could be involved in olfactory signal transduction. Consistent
      with this assumption, it was found that recombinant VILIP attenuates in a calcium
      dependent manner odorant-induced cAMP formation in olfactory cilia preparations.
      Kinetic data indicate that VILIP does not interfere with odorant-induced receptor
      desensitization. Since VILIP inhibits the forskolin-induced formation of cAMP, it
      is conceivable that VILIP may directly affect the olfactory adenylyl cyclase.
      Thus, VILIP may play a role in adaptation of olfactory neurons.

PMID- 9157012
TI  - Concentration of RB protein in nucleus vs. cytoplasm is stable as phosphorylation
      of RB changes during the cell cycle and differentiation.
AB  - Unphosphorylated RB (retinoblastoma tumor suppressor) protein is known to bind
      isolated nuclear matrix in vitro, whereas phosphorylated RB has a lower affinity,
      suggesting a mechanism which might contribute to differential nuclear/cytoplasmic
      localization as part of its regulatory activity. This motivates interest in the
      in vivo localization of the endogenous RB protein as its phosphorylation state
      changes during the cell cycle and cell differentiation. It is known that in
      proliferating HL-60 cells all the RB protein is phosphorylated, but the extent of
      phosphorylation increases with progression from G1 to S to G2 + M. It has also
      been previously shown that retinoic acid and 1,25-dihydroxy vitamin D3 shift the
      RB protein to the unphosphorylated state with cell differentiation (Yen, A., S.
      Varvayanis, Exp. Cell Res. 214, 250-257 (1994)). The dependence of cell cycle
      progression and differentiation on RB nuclear versus cytoplasmic localization, as
      well as the dependence of RB localization on phosphorylation state can thus be
      tested. Confocal image analysis of the RB protein in vivo shows that the ratio of
      the concentration of the RB tumor suppressor gene protein in the nucleus versus
      the cytoplasm remains stable as the RB protein undergoes either phosphorylation
      during cell cycle progression or dephosphorylation during cell differentiation
      induced by retinoic acid or 1,25-dihydroxy vitamin D3. For the cell cycle
      analysis, HL-60 human promyelocytic leukemia cells were fluorescently stained for
      DNA and for the RB protein. G1, S, and G2 + M subpopulations were isolated by
      fluorescence-activated cell sorting. For each subpopulation, the relative
      concentration of RB protein in the nucleus and the cytoplasm was measured by
      laser confocal image analysis. To determine the effect of retinoic acid-induced
      myeloid differentiation or 1,25-dihydroxy vitamin D3-induced monocytic
      differentiation, the same cell sorting and image analysis was performed on cells
      treated with these inducers. In all cases the concentration of the RB protein in
      the nucleus was approximately 2 times that in the cytoplasm. Thus, the ratio of
      nuclear versus cytoplasmic RB protein concentration is stable and independent of
      phosphorylation or dephosphorylation of RB during both the cell cycle and cell
      differentiation.

PMID- 9157013
TI  - Changes in the phosphorylation states of connexin43 in myoepithelial cells of
      lactating rat mammary glands.
AB  - Using specific antibodies and cDNA probe, we examined the expression pattern of a
      major gap junction protein, connexin43 (Cx43), in rat mammary glands during
      pregnancy and lactation. Double immuno-fluorescence revealed that the labeling of
      Cx43 was superimposed in the alpha-smooth muscle actin-positive cells, suggesting
      that myoepithelial cell were interconnected by gap junctions formed of Cx43. Just
      after delivery, the Cx43-labeled plaques were enlarged and increased in
      intensity. Northern and Western blot analyses confirmed the dramatic induction of
      Cx43 at both mRNA and protein levels on the day of parturition. Cx43 mRNA
      transcript immediately declined, while the increase of Cx43 protein continued for
      a few days. During pregnancy, immunoblots showed two bands of almost equal
      amounts at 43 and 45 kDa. Following delivery, the 45-kDa band gradually increased
      in intensity with a concomitant decrease of the 43-kDa band. From the sixth day
      of lactation, Cx43 was always detected as a single band at 45 kDa. Alkaline
      phosphatase treatment of immunoprecipitated Cx43 revealed that both bands
      represented phosphorylated forms, thus indicating that Cx43 was naturally
      phosphorylated and that it altered its phosphorylation states during lactation
      stages. These results suggest that the induction of Cx43 with the changes in the
      phosphorylation states plays an important role in the lactating function of
      myoepithelial cells in rat mammary glands. This is the first report on the
      changes of Cx43 phosphorylation states during physiological stages in vivo.

PMID- 9157014
TI  - A 155-kDa undercoat-constitutive protein of cell-to-cell adherens junctions.
AB  - A fraction enriched in cell-to-cell adherens and tight junctions was isolated
      from the chick liver, and the undercoat-constitutive proteins were extracted from
      this isolated junctional fraction. Monoclonal antibodies (mAbs) were then
      obtained by injecting this extract into rats, and five antigens were identified
      to be concentrated in the isolated junctional fraction. We have characterized one
      mAb (E14 mAb) and its antigen (E14). By immunoblotting of the isolated junctional
      fraction the E14 mAb reacted strongly with a single band of approximately 155
      kDa, and E14 was highly concentrated in the isolated junctional fraction.
      Immunofluorescence microscopy revealed that the E14 mAb exclusively stained the
      junctional complex region of the liver, renal epithelial cells, and the cell-cell
      border of endothelial cells in various tissues. The intercalated disc of the
      heart was also significantly stained. However, the E14 signal was hardly detected
      from intestinal epithelial cells. By immunoelectron microscopy using renal
      epithelial cells, E14 was mainly detected in the fibrous structures associated
      with the cell-to-cell adherens junction. We conclude that E14 is a novel
      undercoat-constitutive protein found in certain types of cell-to-cell adherens
      junctions.

PMID- 9157015
TI  - Macromolecular transport in malaria--does the duct exist?
AB  - The proposal that a parasitophorous 'duct' traverses the malaria-infected
      erythrocyte cytoplasm and is responsible for the unusual molecular uptake
      kinetics observed in malaria, has created considerable debate on the nature of
      macromolecular transport in this parasite. The existence of a 'duct' has
      important implications for the immunobiology of this parasite, particularly the
      possibility that antibodies may have access to 'internal' antigens in malaria.
      The most compelling evidence that there is a direct connection between the
      parasite and the surrounding media comes from the experiment of Pouvelle et al.
      (Nature 353, 73-75 (1991)) using small highly fluorescent latex spheres. However,
      we have found that fluorescent labeling of the parasite and tubular structures
      that extend from the parasite is due to the release of dye from the latex spheres
      during the incubation and is not due to the uptake of the spheres themselves. The
      inability of malaria-infected erythrocytes to take up latex beads down to 14 nm
      diameter establishes that an 'open' channel connecting the parasite with the
      surrounding media does not exist. This finding has important implications for
      establishing the unusual nature of macromolecular transport across the infected
      erythrocyte cytoplasm in malaria.

PMID- 9157017
TI  - Present and future role of calcium antagonists in cardiac protection and
      treatment of coronary artery disease. Nice, France, 14-16 March 1996.
      Proceedings.

PMID- 9157016
TI  - Microtubules are involved in bafilomycin A1-induced tubulation and Rab5-dependent
      vacuolation of early endosomes.
AB  - The small GTPase Rab5 is an important regulator of membrane fusion in the early
      endocytic pathway. Here we have studied at the light microscopy level the
      morphology of early endosomes in MDCK cells stably expressing a GTPase-deficient
      Rab5 mutant, Rab5 Q79L, N-terminally tagged with a myc-epitope. These cells
      contain large vacuoles, readily visible by phase-contrast microscopy. Confocal
      immunofluorescence microscopy showed the presence of the epitopetagged protein on
      large perinuclear vacuoles, as well as on smaller peripheral structures. A subset
      of the perinuclear vacuoles appeared to colocalize with the late endosomal
      GTPase, Rab7. In addition, a population of very large Rab7-positive, Rab5 Q79L
      negative structures were observed, suggesting that an increase in the size of
      early endosomes may be accompanied by an increased size of later or more mature
      endocytic structures. Using antibodies against the myc epitope and the early
      endosomal autoantigen EEA1 as markers, we found that endosomes in wild-type and
      mutant MDCK cells rapidly tubulate in the presence of bafilomycin A1, an
      inhibitor of vacuolar H(+)-ATPase. Elongated or tubular endosomes partially
      colocalized with microtubules and were redistributed upon preincubation with the
      microtubule depolymerizing agent nocodazole before bafilomycin A1 treatment.
      Treatment of the Rab5 Q79L expressing cells with nocodazole alone led to a
      spatial redistribution and a significant decrease in the size of EEA1-positive
      structures, whereas their number increased. These results implicate microtubules
      in the bafilomycin A1-induced tubulation of endosomes as well as in the
      vacuolation of endosomes caused by Rab5 Q79L.

PMID- 9157018
TI  - [The INSERM report "The effects on health of the main asbestos exposures" and the
      decision to ban asbestos in France].

PMID- 9157019
TI  - [A counterfactual approach to epidemiology].

PMID- 9157021
TI  - [True and false prevention].

PMID- 9157020
TI  - [Human error in the anesthesiological field. Up to what point is it possible to
      speak of prevention?].
AB  - Human error (the act of judging true what is false and false what is true) has
      ever played and plays a significant role in the occurrence of incidents during
      anaesthesia. Purpose of the study. The Authors wanted to study how the different
      Authors analyzed the problem and to outline indications for preventive measures.
      Materials and methods. For this purpose we have selected papers and their
      references published on Journals indexed on Index. Medicus (1966-1996). The key
      words have been: anaesthesia or anesthesia, human error, incident and critical
      incident. We analyzed papers where human error in anaesthesia as a source of
      accidents was the main topic. The problem is analyzed starting from a
      classification of different errors and quantified with proper cognitive methods.
      Finally preventive measures are proposed. Results, Contribution of human error to
      the occurrence of accidents in anaesthesia ranges from 37% to 87% according to
      different. Authors employed techniques and sample size. Proper corrective
      measures on human, instrumental and environmental factors can lead to increased
      prevention. Conclusions. Human error exists now and will ever exist. Its gravity
      depends on its consequences and on preventive measures adopted.

PMID- 9157022
TI  - [Risk factors associated with the phenomenon of long-term care in psychiatry. A
      case-control study conducted in the Servizio di Igiene Mentale of Cassentino
      (Arezzo)].
AB  - OBJECTIVE: This work has been carried out to identify any factor associated with
      the long-term treatment through the analysis of all the data concerning the
      sociodemographic, psychosocial, anamnestic and clinical variables existing before
      the disease. MATERIAL AND METHOD: The research, carried out by the Mental Health
      Service in Bibbiena (U.S.A. 21) is a retrospective "case-control" study using a
      sample of 140 patients (70 "cases" and 70 "controls") that had the first contact
      with the psychiatric service in the period 1973-1989. We have defined l'cases"
      those patients who have been treated by the Service on a continuing basis for at
      least 5 years without an interruption more than three months. The "controls" were
      patients selected at random from the same population of "cases", resident in the
      same districts (catchment area of Casentino), but treated for a period shorter
      than 5 years. "Cases" and "controls" were in pairs on the ground of sex, age
      (range +/-5 years) and year of admittance to the service. A doctor of the
      postgraduate school of psychiatry was aware of "case" or "control" state,
      collected all informations using a questionnaire filled in according to medical
      records, psychiatric admission registers and information received by the
      psychiatric service staff. RESULTS: The study suggests that significance risk
      factors for long-term patients are:--diagnosis of schizophrenia. --a history of
      past suicide attempts and assaultive behavior.

PMID- 9157023
TI  - [The "healthy worker effect" or the "exposed general population effect"?].

PMID- 9157024
TI  - [Echinococcosis/hydatidosis in Emilia-Romagna: a study of hospital admissions in
      the period of 1989-1993].
AB  - An overview of the epidemiology human echinococcosis/hydatidosis is presented for
      the Emilia-Romagna region during the period 1989-1993. Data were extracted from
      hospital discharge reports. The description was based on 806 discharges totaling
      10187 days of stay. Thirty-five percent of the patients discharged were residents
      outside the Emilia-Romagna region. A significant statistical correlation was
      identified between a high average yearly incidence of the disease and a
      relatively small jurisdiction of residency. No correlation was established
      between average yearly incidence and number and density of sheep and goats and
      farms and estimated dogs.

PMID- 9157027
TI  - [Inferences, Philip Morris and the bibliographic impact factor].

PMID- 9157026
TI  - [The evaluation of day hospital activities: an analysis of intervention protocols
      and a comparison between the indicators of the activities of the day hospital and
      of the regular admission].
AB  - Day hospital (DH) activity may avoid in-staying of patients resulting in an
      increase of efficiency and in a more satisfying diagnostical-therapeutical
      process for the patient. All the same, it is quite difficult to identify
      parametres and indicators to be used in the evaluation and quantification of DH,
      so that both scientific literature reporting experiences and law are lacking. One
      of the reasons is probably due to the lack of nosological characterization of
      patients and protocols of DH activity, so that the definition relies only on
      organizational and technical parameters. Characterization of protocols of
      intervention is the basic approach to the present DH investigation. Parameters
      such as: multiplicity of services, weekly planning of the activity and
      surveillance needed by the patient are considered the fundamental criteria to
      identify and quantify DH in the present research carried out at the University
      Regional Hospital of Pisa. The aim of this article is, on one side, to give a
      methodology of investigation based, as far as possible, on "explicit" indicators
      and parameters, so that the experience may be exported into other contexts and on
      the other, to give an example of resource analysis and efficiency evaluation
      which were internally used for "audit" review.

PMID- 9157025
TI  - [A seroepidemiological study on the level of immunological coverage in a nomadic
      population in Rome].
AB  - Immunization status to the three types of poliovirus, to tetanus, diphtheria and
      measles was evaluated in a Gypsy population living at a Roman camp. Information
      about demographic data and history of immunization was collected from 149
      subjects and a blood sample was obtained from 86 individuals to determine
      antibody titres to the above mentioned infectious agents. Among the responders,
      only 20.8% had received at least one dose of oral polio vaccine (OPV), tetanus
      and diphtheria vaccine, while none was vaccinated against measles. In spite of a
      low immunization coverage, serological data showed high prevalence of antibodies
      to the three types of poliovirus (81.4% to polio type 1:94.2% to polio type
      2:62.8% to polio type 3) and to measles (76.7%), while antibodies to tetanus and
      to diphtheria were detected respectively only in 3.5% and 0% of the individuals
      tested. High levels of antibodies to polio were found also among unvaccinated
      subjects. For these, a statistically significant positive correlation between age
      and number of "contact doses" from vaccinated family members was observed (r =
      0.70; CI 95%: 0.27-0.90). In conclusion, this study uncovers very low levels of
      immunization to poliovirus, tetanus, diphtheria and measles in the study Gypsy
      population, and shows the effects of the secondary spread of the OPV, which
      probably contributed to reduce the risk of contracting the disease in
      unvaccinated individuals.

PMID- 9157028
TI  - [The judgement of the Civil and Criminal Court of Turin, Section II, in the suit
      of the British Asbestos Company Limited versus Il Progresso del Canavese e delle
      Valli di Stura (31 August 1906)].

PMID- 9157029
TI  - Selections from current literature: PSA screening for prostate cancer.

PMID- 9157030
TI  - [Callus distraction for progressive lengthening of the capitate bone after
      resection of the lunate bone in stage III lunate malacia. Surgical technique and
      1 year results].
AB  - Inspite of the excellent subjective judgement and functional results of Graner's
      operation in case of Kienbock's disease stage III, this technique is rarely used
      nowadays because of its high rate (20 to 30%) of disturbed fracture healing due
      to impaired blood supply. To avoid the risk of complete devascularization in the
      capitate region, we are using the callotaxis lengthening technique of Ilizaron,
      carrying out a segmental shifting. After percutaneous temporary SC- or STT
      arthrodesis with the scaphoid in the horizontal or high position, the lunate is
      completely resected using a dorsal approach. Osteotomy of the capitate is carried
      out at the corpus-collum interval in order to disturb a minimum of the vascular
      supply to the bone. Seven to ten days postoperatively, distraction is started
      with a rate of 1 min/day. The desired distraction length is accomplished, when
      the capitate articular surface fits perfectly into the curvature of the proximal
      row articular surface. In order to reduce or prevent soft tissue related
      complications during the consolidation period, the external distractor is
      replaced by two percutaneous Kirschner-wires. The consolidation period takes
      twice as long as the distraction period. Since November 1993, fourteen patients
      presenting a stage III Kienbock's disease have been treated by this new
      technique. The operative technique, postoperative care, as well as the potential
      and real complications are described and illustrated by one clinical case.

PMID- 9157031
TI  - [Fate of the calcium-dense proximal fragment in scaphoid fracture].
AB  - A cohort study with retrolective and prolective collection of data was carried
      out 49 of 99 patients with scaphoid fractures, initially treated by plaster cast
      immobilization and having developed a proximal fragment with increased bone
      density were studied. More than half of these patients had a good or excellent
      result according to the modified score of Green and O'Brien 29 of 49 proximal
      fragments with increased bone density returned to normal density: 45 of 49 showed
      bony union, and 35 of 49 showed no signs of posttraumatic arthrosis. The
      appearance of stripes with increased bone density in plain X-rays indicated a
      problem in the process of fracture healing; the clinical interpretation, however,
      was difficult. Four patients were treated by percutaneous canulated screw
      (Streli). These fractures showed bony union, the fragment with increased bone
      density returned to normal in three of four patients. All of these patients had
      some remaining clinical problems.

PMID- 9157032
TI  - [Pseudarthrosis of the capitate bone. Report of 2 cases].
AB  - Well protected by its central position and richly vascularized, the capitate bone
      is rarely involved in posttraumatic pseudarthrosis. Drawing on two cases, the
      present study will describe anatomy, aetiology, pathogenesis, diagnosis, and
      therapy of pseudarthroses of the capitate. Restoration of the physiological
      capitate height was achieved in both cases with a corticocancellous bone graft
      from the iliac crest which led on to bony union within three months.

PMID- 9157033
TI  - [Stress on the radiocarpal joint. CT studies of subchondral bone density in
      vivo].
AB  - Most concepts about the mechanism of load transmission through the radiocarpal
      joint have been mostly acquired from the study of cadaveric specimens. Apart from
      this, however, it is possible to derive direct knowledge about the actual
      mechanical conditions of a joint from certain morphological parameters,
      particularly by analysis of the subchondral mineralization. CT
      osteoabsorptiometry (CT-OAM) has provided a non-invasive investigative tool by
      which the distribution of subchondral mineralization within the radiocarpal joint
      can be determined. Seventeen wrist-joints in healthy young subjects were
      investigated by means of CT-OAM, and the results evaluated both topographically
      and quantitatively. In most cases, two density maxima were found on the articular
      radial surface, one corresponding to the scaphoid and one to the lunate. These
      matched the positions of pressure peaks described in reports of research on
      mechanical models. The density maximum on the articular surface of the radius
      opposing the scaphoid is, however, rather more dorsally placed, whereas that
      opposing the lunate lies palmar to the radioulnar midline. This explains the
      transmission of force to the forearm and the geometrical configuration of the
      joint components. On the other hand, our quantitative results do not confirm the
      existence of a generally greater degree of mineralization of either one of the
      joint compartments. We cannot confirm theories attributing transmission of the
      main force through either the scaphoid or the lunate. We assume rather that the
      type of stress indicated by the predominantly monocentric density maxima either
      on the scaphoid or the lunate surface of the radius, together with the equally
      balanced bicentric degree of mineralization, are to be regarded as physiological.

PMID- 9157034
TI  - [Anesthesia and analgesia in intravenous drug dependent patients with injection
      abscesses of the upper extremity. Case report].
AB  - The morbidity and mortality rate of drug addicts is characteristically higher
      than in a normal population. Especially abscesses of the hand and the forearm
      region are frequent consequences of unsterile injection techniques. Pre-, intra-,
      and postoperative anaesthetic management has to take into consideration that the
      choice of the anaesthetic procedure should not interfere with the very special
      conditions of the drug addicts. In our experience, continuous axillary brachial
      plexus block offers a number of advantages in pain management in drug addicts as
      well as in former drug addicts.

PMID- 9157035
TI  - [The hand, treasure and honor of mankind].

PMID- 9157036
TI  - [Fresh injuries of the tractus intermedius of the extensor aponeurosis.
      Diagnosis, classification and therapy].
AB  - A test for early diagnosis of closed isolated ruptures of the central slip of the
      extensor hood is described. Five different lesions are described. Conservative
      treatment is adequate for ruptures with undislocated bone fragments. Operative
      treatment is required when the central slip has been avulsed with a dislocated
      bone fragment, in cases of combined lesions of the PIP joint (including central
      slip, collateral ligaments and/or the palmar plate) and finally open lesions. An
      isolated closed rupture of the central slip is a relative indication for surgery
      and is treated conservatively under specified circumstances.

PMID- 9157037
TI  - [Restoration of grip function in both hands after frostbite of all fingers and
      toes. A case report].
AB  - Evaluation, therapeutical possibilities, and surgical planning for the
      restoration of bilateral grip function are described, based upon a 34-year-old
      engineer presenting after severe bilateral frostbite of the hands and feet with
      loss of all fingers and toes. Finally, the given level of amputation and
      remaining components of the hand together with distraction-lengthening of both
      thumbs permitted restoring a basic grip on both sides in combination with bone
      and soft tissue procedures.

PMID- 9157038
TI  - [Diseases of the esophagus in the elderly. Deglutition disorders--intermittent
      thoracic pain--retrosternal burning pain].
AB  - As a contribution to the polymorbidity of geriatric patients, gastrointestinal
      diseases are numerically of only minor importance, occurring four to five times
      less frequently than diseases of the cardiovascular system. However, a number of
      gastrointestinal diseases are more commonly found in the elderly than in the
      younger patient. The symptoms of esophageal diseases include dysphagia,
      odynophagia, pyrosis, and intermittent chest pain. New developments in the area
      of drug treatment, and minimally invasive endoscopic procedures usually now
      permit age adaptet therapeutic management to be offered.

PMID- 9157039
TI  - [Deglutition disorders in the elderly--also consider neurogenic causes].

PMID- 9157040
TI  - [Reflux causes esophageal disorders especially in the elderly. Interview by Dr.
      rer. Nat. Anita Schweiger].

PMID- 9157041
TI  - [Suitable diet can modify esophageal disorders. Nutrition should be adapted to
      the specific illness].

PMID- 9157043
TI  - [Gram negative folliculitis. A complication of antibiotic therapy of acne
      vulgaris. 2: Diagnosis and differential diagnosis--therapy].

PMID- 9157042
TI  - [Healing practitioner--a German phenomenon. What are the rights and
      responsibilities of healing practitioners?].
AB  - The "Heilpraktiker" is a German phenomenon dating back to the Third Reich. Today,
      there are between seven and ten thousand practicing "Heilpraktiker" in Germany.
      The training, skills, responsibilities and rights of this profession do not
      accord with the law that aims to "avert a danger to the health of the people". In
      Brussels, harmonization of the area of nonmedically trained practitioners is
      presently under discussion. However, a speedy solution to the obvious problems is
      not yet in sight.

PMID- 9157044
TI  - [Needlestick injury with infectious material--what is the procedure?].

PMID- 9157045
TI  - [Effect of ultraviolet irradiation on the vascular bed of the skin].

PMID- 9157046
TI  - [Cost structure of hepatitis B infection].

PMID- 9157047
TI  - [MDMA ("Ecstasy") use--an overview of psychiatric and medical sequelae].
AB  - Epidemiological research and Substance Abuse Warning Systems point to a sharp
      increase in the use of "Ecstasy" (MDMA), as well as to structural changes in the
      drug scene in and outside Europe. For some consumers, "Ecstasy" opens the door to
      the abuse of other illegal substances. Since the mid-eighties psychiatric
      complications and consequences of the abuse of MDMA have been reported in at
      least 48 cases. It is necessary to differentiate between acute psychiatric
      complications, which subside completely when the level of intoxication comes
      down, toxic psychoses and long-term psychiatric diseases as a consequence of
      substance abuse. The latter involve atypical and paranoid psychoses, depressions,
      panic disorders, depersonalisation and behavioural disorders. Convulsive seizures
      are among the most common problems involving the central nervous system.
      Furthermore, there have been reports on cerebrovascular accidents and
      intracranial haemorrhages. Literature reports on at least 53 cases of medical
      complications in abusers of MDMA, 14 of which came to a lethal end. Research
      still blatantly lacks prospective epidemiological and clinical studies on a
      sufficiently large scale to identify different developments of dependency and
      predictors of harmful and unhealthy consumption.

PMID- 9157048
TI  - [Conrad Ferdinand Meyer reflected in the paradigm change in German psychiatry].
AB  - German-speaking psychiatrists had a great interest in the Swiss poet and writer
      Conrad Ferdinand Meyer (1825-1898)-even after his death. Meyer was hospitalised
      twice for major depression with psychotic features. For many years of his life he
      showed a chronic depressive disorder. We would diagnose a dysthymic disorder with
      comorbid recurrent major depressive disorder with psychotic features according to
      DSM-IV or ICD-10. After Meyer had lived isolated for many years and had hardly
      left his house, he reached public recognition and found his "profession" only at
      the age of 40. Different pathographic publications (amongst others Mobius,
      Hellpach, Sadger, Lang, Jung) on Meyer in the early 20th century reflect the
      debate over both Kraepelin's theories and psychoanalysis. In these publications
      the scientific argument was often more important than Meyer's biography. Two
      topics play an important role in these discussions: the differences between
      idiographic and nomothetic method, and the question, where the border between
      "personality variation" and "illness" lies.

PMID- 9157049
TI  - [Genital self-injury behavior--phenomenologic and differential diagnosis
      considerations from the psychiatric viewpoint].
AB  - There is only a small number of publications concerning psychiatric aspects of
      genital-self-mutilation, all of these are case reports. This presentation adds
      results of self-inflicted genital injuries in another seven males which are
      discussed in relation to relevant scientific literature focussing on
      psychopathology and dynamic considerations. It is argued that genital self
      mutilations should primarily be considered as symptomatic behavioural patterns
      and that-beside quasi-normal psychological procedures as part of certain
      religious or cultural rituals-such acts can be interpreted as a common final
      pathway of a variety of psychopathological problems. The inclusion of sexually
      (co-)motivated genital-automutilations in a complete work up and analysis of this
      topic seems to be reasonable and is advocated by the authors. The assumption that
      genital self-injuries are more often seen in non-psychotic conditions than in
      productive psychotic states is substantiated. Finally, the relation between
      genital automutilations and self-harm in general is discussed and some
      recommendations on the management are listed.

PMID- 9157050
TI  - [Genetic diagnosis, classification and clinical hereditary ataxia disease
      entities].
AB  - Hereditary ataxias are a heterogeneous group of neurodegenerative diseases.
      Neither the clinical features nor the findings at autopsy provide a satisfactory
      basis for the isolation of distinct categories and classification. Recently,
      several gene loci responsible for inherited ataxias have been identified. For
      several hereditary ataxias even the disease causing mutations have been
      described. These findings lead to a new classification of the inherited ataxias
      based on genotypes rather than pathology or phenotypes. Such a classification
      will potentially gain wide acceptance since it derives from the molecular genetic
      cause of the diseases. Furthermore, recent advances in molecular biology improved
      the understanding of the clinical variability of hereditary ataxias that occurs
      even within the same family. All forms of progressive dominant ataxias are most
      likely caused by the same type of mutation: an unstable and expanded
      trinucleotide repeat. The repeat expansion is moderate in patients with later
      onset and mild progression but is extensive in juvenile cases with a more rapid
      course of the disease. Furthermore, the extent of the expansion seems to be at
      least partially responsible for the development of different phenotypes. The
      identification of gene loci and mutations allows reliable diagnosis even at a
      presymptomatic or prenatal stage for an increasing number of inherited ataxias.
      Although molecular genetics has improved the diagnosis and understanding
      considerably for most forms of hereditary ataxias a causal therapy is still
      missing. Therefore, it is essential that presymptomatic analysis is always
      performed according to the international guidelines. They include genetic
      counselling by a team of experienced neurologists, geneticists, psychologists and
      social workers.

PMID- 9157051
TI  - [CADASIL: 2 case reports of hereditary multi-infarct dementia].
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is a hereditary stroke disease linked to chromosome
      19 q 12. We report on two families affected by this disease, which is
      characterised by recurrent subcortical ischaemic strokes, progressive
      pseudobulbar palsy, and presenile dementia. Neuroimaging revealed multiple deep
      infarcts and diffuse leukoencephalopathy. Diagnosis of CADASIL based on the
      typical clinical feature without vascular risk factors, the neuroradiological
      signs of extensive leukoencephalopathy, and the autosomal dominant pattern of
      inheritance. CADASIL might be an underestimated cause of familial stroke and
      should be considered in the differential diagnosis of hereditary stroke.

PMID- 9157052
TI  - Immunological detection of lipopolysaccharide antigens of thermophilic
      campylobacters captured on polymyxin-coated polyester cloth.
AB  - Cholate-extracted lipopolysaccharide (LPS) antigens from thermophilic
      campylobacters were captured on polymyxin-coated polyester cloth. The captured
      antigens were detected by sequential reactions with rabbit anti-Campylobacter
      antibody, anti-rabbit IgG peroxidase conjugate and chromogenic peroxidase
      substrate. A polyclonal rabbit antibody elicited against a single Campylobacter
      jejuni strain detected the reference strains of the twenty most frequently
      isolated thermophilic campylobacters in the Lior serotyping scheme. Moreover, LPS
      antigens of six C. Jejuni Penner serotypes fractionated by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and examined by immunoblotting were recognized
      by four antisera prepared against homologous and heterologous Penner serotypes.
      The results suggest the potential application of polymyxin-cloth enzyme
      immunoassay for rapid detection of thermophilic campylobacters where monoclonal
      antibodies can be raised to possible common LPS epitopes.

PMID- 9157053
TI  - Neutrophil function in elderly persons assessed by flow cytometry.
AB  - It is well known that the immune response declines with senescence and it is
      suggested that these changes render an individual susceptible to infection,
      autoimmune phenomena and cancer. Bacterial and viral infections are a major cause
      of illness and death amongst aged subjects, and once infection is established,
      the elderly also have a diminished capacity to prevent its spread (1). The
      cellular and molecular basis for this age-related decline in immunocompetence are
      still unknown and, possibly, are related to an alteration in cell transduction
      mechanisms (2).

PMID- 9157054
TI  - Immunoregulatory effect of substance P in human eosinophil migratory function.
AB  - Substance P (SP) is a tachykinin involved in the regulation of inflammatory
      processes. To investigate a modulatory role of the neuropeptide SP in allergic
      inflammation, we studied its priming effect on human eosinophil chemotaxis and
      kinetic responses towards platelet activating factor (PAF) and recombinant human
      interleukin 5 (rhIL-5). Blood was obtained from normal subjects and eosinophils
      were separated by Percoll discontinuous density gradient centrifugation. High
      purification was obtained by negative selection procedure (CD16-beads) and the
      experiments were performed in a 48-well microchemotaxis Boyden chamber. In the
      present study we demonstrate a potent synergistic effect of 1OOnM dose of SP on
      the migratory function of human eosinophils stimulated by PAF and rhIL- 5. This
      synergism was chemotaxis specific and was abolished by NK-1 receptor antagonist
      (FK888). The results suggest that neurogenic stimuli may play a significant role
      in eosinophil infiltration via its priming effect on the cell.

PMID- 9157055
TI  - [Biology and molecular pathology of Hodgkin's disease].

PMID- 9157056
TI  - [Histopathology and classification of non-Hodgkin's lymphoma].

PMID- 9157057
TI  - [Current status of therapy of follicular germ center lymphoma and mantel cell
      lymphoma].

PMID- 9157058
TI  - [Treatment of aggressive non-Hodgkin's lymphoma].

PMID- 9157059
TI  - [Therapy of recurrent high-grade non-Hodgkin's lymphoma].

PMID- 9157060
TI  - [Immunotherapy strategies in lymphoma].

PMID- 9157061
TI  - [Hyponatremia and renal sodium loss in a patient after resection of an
      intracerebral tumor].

PMID- 9157062
TI  - [Dens axis fracture, spinal pain and hematemesis].

PMID- 9157063
TI  - [Patients with coronary heart disease and post-myocardial infarct status].

PMID- 9157064
TI  - [Diuretics in therapy of hypertension?].

PMID- 9157065
TI  - [Is supplemental vitamin E for prevention of coronary heart disease ov value?].

PMID- 9157066
TI  - [Diagnosis and therapy of thyroid gland diseases. Recommendations for quality
      assurance].

PMID- 9157067
TI  - [Tests of endocrine function].

PMID- 9157068
TI  - Cellular transport of CI-980.
AB  - CI-980, originally synthesized as a potential folate antagonist, is a tubulin
      binding mitotic inhibitor currently in pediatric phase I and adult phase II
      clinical trials. Because of its extensive tissue distribution in animals and its
      favorable activity against multidrug resistant (MDR)-cells compared with other
      mitotic inhibitors, such as vincristine, we examined the membrane transport
      properties of CI-980. CI-980 accumulated rapidly in L1210 and CHO/K1 cells,
      reaching intracellular levels 40- and 8-fold higher, respectively, than those in
      the extracellular medium. Efflux was also quite rapid, but a small fraction of
      drug remained associated with the cells in drug-free medium. The uptake of CI-980
      was not temperature or energy dependent, nor was it saturable up to an
      extracellular concentration of 100 microM. Inhibitors of nucleoside transport had
      no effect on CI-980 uptake. A cell line deficient in the transport of reduced
      folate was not resistant to CI-980, nor did it exhibit reduced CI-980 uptake. A
      100-fold excess of the R-enantiomer inhibited CI-980 uptake by only 50%. These
      results are consistent with a model of CI-980 uptake involving passive diffusion
      followed by significant but largely reversible binding to intracellular or
      membrane components.

PMID- 9157069
TI  - Preclinical antitumor activity of CI-994.
AB  - CI-994 [aka: acetyldinaline; PD 123654; 4-acetylamino-N-(2'aminophenyl)
      benzamide] (Figure 1) is a novel antitumor agent with a unique mechanism of
      action. It is the acetylated metabolite of dinaline, a compound previously
      identified as having cytotoxic and cytostatic activity against several murine and
      human xenograft tumor models. CI-994 had activity against 8/8 solid tumors tested
      (log cell kills at the highest non-toxic dose): pancreatic ductal adenocarcinoma
      #02 (4.7); pancreatic adenocarcinoma #03 (3.0; 1/6 cures); colon adenocarcinoma
      #38 (1.6); colon adenocarcinoma #51/A (1.1); mammary adenocarcinoma #25 (1.7);
      mammary adenocarcinoma #17/ADR (0.5); Dunning osteogenic sarcoma (4.0); and the
      human prostate carcinoma LNCaP (1.2). CI-994 had the same spectrum of activity in
      vivo as dinaline. It also behaved similarly in schedule comparison/toxicity
      trials. Prolonged administration with lower drug doses was more effective than
      short-term therapy at higher individual doses. If doses were kept between 40 and
      60 mg/kg/injection, prolonged administration (> 50 days) was tolerated with no
      gross toxicity. Doses > or = 90 mg/kg/injection caused lethality after 4-5 days
      of administration. The maximum tolerated total dose was also increased with
      smaller individual doses administered for prolonged intervals. Clinical Phase I
      trials are ongoing with this agent.

PMID- 9157070
TI  - Effects of 13-hydroxy SM5887 in combination with other anticancer agents on human
      tumor cell lines.
AB  - A new anthracycline derivative, SM5887, in combination with commonly used
      anticancer agents was evaluated against T-cell leukemia MOLT-3 and human
      osteosarcoma MG-63 cell lines in culture. MOLT-3 and MG-63 cells were incubated
      with various concentrations of 13-hydroxy SM5887 (SM5887-OH, the active
      metabolite of SM5887) and other drugs for 3 and 4 days, respectively. Cell growth
      inhibition was determined by MTT assay. The antitumor effects of the drug
      combinations at 80% inhibitory concentration (IC80) were analyzed by the
      isobologram of Steel and Peckham. In MOLT-3 cells, SM5887-OH had additive effects
      with bleomycin, etoposide, doxorubicin, cisplatin, mitomycin-C, 4-hydroperoxy
      ifosfamide, 5-fluorouracil, cytarabine, and vincristine, whereas it had mainly
      protective (marked antagonistic) effects with methotrexate. In MG-63 cells,
      SM5887-OH had additive effects with bleomycin, etoposide, doxorubicin, cisplatin,
      mitomycin-C, 4-hydroperoxy ifosfamide; mainly subadditive (mild antagonistic)
      effects with 5-fluorouracil and cytarabine; and mainly protective (marked
      antagonistic) effects with vincristine and methotrexate. These findings suggest
      that SM5887 is suitable for simultaneous administration with bleomycin,
      etoposide, doxorubicin, cisplatin, mitomycin-C, or ifosfamide and not suitable
      for simultaneous administration with methotrexate. The effects of SM5887 in
      combination with 5-fluorouracil, cytarabine or vincristine may be variable,
      depending on cell lines. To find optimal combinations, further in vitro and in
      vivo studies of antitumor activity and toxicity appear to be warranted.

PMID- 9157071
TI  - Murraya koenigii and Brassica juncea--alterations on lipid profile in 1-2
      dimethyl hydrazine induced colon carcinogenesis.
AB  - The influence of the two commonly used spices Murraya koenigii (curry leaf) leaf
      and Brassica juncea (mustard) seeds on the levels of lipids, fecal bile acids and
      neutral sterols was studied in rats administered 1,2-dimethyl hydrazine (1,2
      DMH). The levels of cholesterol and phospholipids decreased in the experimental
      groups when compared with the control. The cholesterol phospholipid ratio showed
      an elevated level in the DMH treated control compared with the species group.
      Bile acids and neutral sterols showed a sharp increase in the spices treated
      groups in liver and feces when compared with the control. Morphological and
      histological studies revealed that the mean number of neoplasms in the colon and
      intestine were significantly low in the spices fed groups.

PMID- 9157072
TI  - Clinical phase I and pharmacokinetic trial of vinorelbine administered as single
      intravenous bolus every 21 days in cancer patients.
AB  - We have performed a high-dose clinical and pharmacokinetic trial with vinorelbine
      administered as a bolus injection every 21 days. The aim was to evaluate a
      schedule with longer treatment intervals than one week and to determine the
      toxicity pattern of such a schedule. A total of 13 patients (pts) with solid
      tumors (non-small-cell lung [3 pts], unknown primary [3 pts], mesothelioma [2
      pts], colon/rectum, sarcoma, thyroid, head/neck and cervix [1 pt each]) were
      entered [9 male, 4 female, median age: 56 years (range: 37-69)]. Dose levels were
      35, 40 and 45 mg/m2 with a total of 26 cycles administered. At 40 mg/m2, 2/6 pts
      developed grade 4 granulocytopenia. 1/1 pt at 45 mg/m2 developed a grade 4 leuko-
      and granulocytopenia. Non-hematological toxicities were mild to moderate.
      Neurologic toxicity except for constipation was mild. Constipation occurred at 35
      mg/m2 in 1/6 pts WHO grade 4, at 40 mg/m2 in 2/6 pts WHO grade 3 and at 45 mg/m2
      in 1/1 pt WHO grade 4 and was due to neurotoxicity. No objective antitumor
      response was observed. Vinorelbine pharmacokinetics were analysed in whole blood
      and plasma and were similar to previously published studies using < or = 30
      mg/m2. Our results confirm a high affinity of vinorelbine to corpuscular blood
      elements. We conclude that the MTD of vinorelbine administered once every 21 days
      as bolus injection is 40 mg/m2, the dose-limiting toxicities are constipation and
      granulocytopenia and the recommended dose for subsequent Phase II trials is 35
      mg/m2.

PMID- 9157073
TI  - Clinical and pharmacokinetic phase I trial of oral dimethylaminoetoposide (NK611)
      administered for 21 days every 35 days.
AB  - We have conducted a clinical and pharmacokinetic trial of the novel
      podophyllotoxin derivative NK611 administered orally for 21 consecutive days. The
      treatment was repeated every 35 days. Eighteen patients were included into the
      study, all of whom were eligible. Due to early progression of tumor disease in
      two patients, 16 patients were evaluable for toxicity [7 female, 9 male, median
      age 64 years (range: 44 to 73)]. Dose escalation steps were 5 mg/day [105 mg per
      cycle (pc)], 10 mg/day (210 mg pc), 12.5 mg/day (265 mg pc) and 15 mg/day (315 mg
      pc). A total of 37 courses was administered. Toxicity was evaluated using NCI-CTC
      criteria. Granulocytopenia was the main hematologic toxicity. Other hematologic
      toxicities were sporadic. Non-hematologic toxicities were mild and consisted of
      grade 1 nausea and grade 2 alopecia. Pharmacokinetic analyses were performed in
      six patients each treated with 10 mg/day and 12.5 mg per day, and in one patient
      treated with 15 mg/day. Using a two-compartment model, t1/2 alpha ranged from
      0.47 to 1.54 h and t1/2 beta from 2.0-11.6 h. Mean values for Cmax and AUC were
      1.47 +/- 0.331 microgram/ml and 13.67 +/- 3.81 micrograms/ml.h. No objective
      tumor responses were observed. However, one patient with metastatic breast cancer
      had stable disease for twelve months. We conclude that the Maximum Tolerated Dose
      of NK611 administered daily for 21 consecutive days is 12.5 mg/day. The Dose
      Limiting Toxicity is granulocytopenia. The recommended dose for further clinical
      Phase II studies is 10 mg/day.

PMID- 9157074
TI  - Phase I trial of recombinant platelet factor 4 (rPF4) in patients with advanced
      colorectal carcinoma.
AB  - BACKGROUND: Recombinant platelet factor 4 (rPF4) is a naturally occurring protein
      found in platelet alpha granules that can inhibit angiogenesis. METHODS: In this
      Phase I trial, 9 patients with metastatic colorectal cancer who had failed 5-FU
      treatment received rPF4 at doses ranging from 0.3 to 3.0 mg/kg via 30-minute
      infusion. Three additional patients were treated with the 3 mg/kg dose over a 6
      hour period of infusion. RESULTS: The only toxicity encountered was mild leg
      twitching in 2/3 patients treated with the 6-hour infusion. One patient with a
      history of phlebitis developed a lower extremity deep venous thrombosis after the
      first dose of rPF4. A mild rise in fibrinogen level was noted in several
      patients. Of the 11 evaluable patients, there were no clinical responses to
      treatment. CONCLUSIONS: rPF4 is well tolerated at the doses and schedules tested.
      No clinical responses were observed. Prolonged infusion schedules should be
      investigated.

PMID- 9157075
TI  - 13-Cis-retinoic acid and interferon alpha-2a in patients with advanced esophageal
      cancer: a phase II trial.
AB  - The aim of this study was to investigate the possible therapeutic effect of 13
      cis-retinoic acid plus interferon alpha-2a in patients with inoperable squamous
      cancer of the esophagus. Patients with advanced, measurable, histologically
      confirmed squamous carcinoma of the esophagus with an Eastern Cooperative
      Oncology Group (ECOG) performance status of 0, 1 or 2 who had adequate bone
      marrow, liver, and renal function were eligible for study. Patients were given
      cis-retinoic acid 1 mg/kg/day per mouth continuously and interferon alpha-2a 3
      Mu/day for 3 days followed by 6 Mu subcutaneously daily thereafter. Seventeen
      patients were entered on study. Fifteen patients were evaluable for toxicity. The
      most common toxicities were grade 1 and 2 cheilitis, dry skin and flu-like
      symptoms which occurred in all patients. Two patients had grade 3 toxicity (1
      anorexia and 1 fatigue). No grade 4 toxicity occurred. Fifteen patients were
      evaluable for response. No objective response was documented. The median survival
      time was 15 weeks. With no response seen it is unlikely that the combination of
      treatment as used in this study will be of benefit in patients with advanced
      squamous cancer of the esophagus.

PMID- 9157076
TI  - A phase II trial of a differentiating agent (tRA) with cisplatin-VP 16
      chemotherapy in advanced non-small cell lung cancer.
AB  - The prognosis for advanced non-small cell lung cancer remains poor. Response to
      chemotherapy is infrequent and overall survival is low. Trans-retinoic acid
      (tRA), a differentiating agent whose mechanism of action is thought to be
      different from conventional chemotherapy has activity in preclinical models and
      low but definite activity in the clinical setting. Its use has been hampered by
      decrease in bioavailability during continuous administration. We used an
      interrupted dosing schedule with a drug holiday for tRA that has since been
      confirmed to restore blood levels in combination with chemotherapy (Cisplatin-VP
      16) in 20 patients with stage IIIB and IV non-small cell lung cancer. Ten
      patients had partial responses among 19 evaluable pts (53%; 95% confidence
      interval 30-75%) and 4 had minor responses. Neutropenia was the most common acute
      toxicity-grade 3/4 neutropenia occurring in 90% of patients at some point in the
      treatment course. Median survival was 25.5 weeks. This regimen of trans-retinoic
      acid given with drug holiday and chemotherapy has significant activity in
      advanced non-small cell lung cancer, is fairly well tolerated and is worthy of
      confirmation in a larger, multi-institutional setting.

PMID- 9157077
TI  - Evaluation of topotecan in patients with recurrent for metastatic squamous cell
      carcinoma of the head and neck. A phase II Southwest Oncology Group study.
AB  - Twenty-nine patients with persistent, recurrent and/or metastatic squamous cell
      carcinoma of the head and neck were treated daily for five days at three-week
      intervals with topotecan 1.5 mg/m2. Four patients received prior chemotherapy, 23
      prior surgery and 29 prior radiation therapy. Of the 29 eligible patients, 8
      patients were not evaluable for response and were assumed to be non-responders.
      Of the remaining 21 evaluable patients, there were zero responses (0%, 95%
      confidence interval [0,.12]). The most common toxicities were myelosuppression,
      dyspnea and malaise/fatigue/lethargy. Topotecan has limited activity in advanced
      head and neck cancer with this dose and schedule.

PMID- 9157078
TI  - A phase II trial of amonafide, caracemide, and homoharringtonine in the treatment
      of patients with advanced renal cell cancer.
AB  - Forty-eight previously untreated, ambulatory patients with advanced or
      unresectable renal carcinoma were treated with either amonafide (17 patients),
      caracemide (17 patients), or homoharringtonine (14 patients). No objective
      responses were observed in any of the treatment cohorts. Amonafide and caracemide
      were well tolerated with no unexpected toxicities. One patient each died of
      pulmonary thromboembolism and sepsis with severe metabolic acidosis on the
      homoharringtonine arm. An additional 4 patients experienced grade 4 complications
      including myelosuppression, neurologic dysfunction, and respiratory failure.
      These severe and unexpected complications caused early termination of accrual to
      the homoharringtonine arm of the study. These agents have no activity in the
      treatment of advanced renal cell carcinoma.

PMID- 9157081
TI  - The integration of clinical skills and clinical anatomy in medical education.

PMID- 9157079
TI  - Phase II study of mitonafide in non-small cell lung cancer (NSCLC).
AB  - BACKGROUND: The new intercalative agent Mitonafide was shown in early clinical
      trials to be toxic to the central nervous system when administered as a short
      intravenous infusion, but not when given as a 120-hour continuous infusion. Thus,
      clinical development in different tumor types was pursued using only this
      administration schedule. PATIENTS AND METHODS: Forty-nine patients with
      previously untreated non-small cell lung cancer (NSCLC) and at least one
      measurable site received Mitonafide as a 120-hour continuous (5 days) infusion
      every 3 weeks. The starting dose was 170 mg/m2/day x 5 in the first 26 patients
      and 200 mg/m2/day x 5 in the remainder. Patients were evaluated for toxicity
      after each course and for response every two courses and remained on treatment
      until excessive toxicity or disease progression were observed. A special test,
      the "Mini-mental state", was used to assess patients' cognitive functions.
      RESULTS: Of the 49 patients entered, 42 were evaluable for response and toxicity.
      Toxicity consisted mainly of myelosuppression and no neurologic side effects were
      observed. Only one patient presented a partial response. CONCLUSIONS: Although
      definitively safe with this schedule of administration, Mitonafide is not active
      in NSCLC.

PMID- 9157080
TI  - Phase II trial of low-dose N-(phosphonacetyl)-disodium L-aspartic acid and high
      dose 24-hour infusional 5-fluorouracil in advanced gastric adenocarcinoma. A
      Southwest Oncology Group study.
AB  - N-(phosphonacetyl)-disodium L-aspartic acid (PALA) demonstrates a synergistic
      antitumor effect when combined with 5-Fluorouracil (5-FU) in in vitro studies. In
      a Phase II trial, 23 eligible patients with unresectable or metastatic
      adenocarcinoma of the stomach were treated with weekly i.v. bolus PALA (250
      mg/M2) followed 24 hours later by a 24-hour infusion of 5-FU (2600 mg/M2) for an
      initial period of 8 weeks. No objective responses were noted. PALA and 5-FU is
      inactive against gastric adenocarcinoma at the doses and schedule used in this
      trial.

PMID- 9157082
TI  - [Differential therapy of chronic wounds].

PMID- 9157083
TI  - Indirect allorecognition of HLA class I peptides by CD4+ cytolytic T lymphocytes.
AB  - T-cell responses to alloantigens can occur either by "direct" recognition of
      donor MHC molecules, or "indirect" recognition of MHC peptides in association
      with self-MHC. To evaluate human T cells mediating indirect allorecognition, a
      CD4+ TCL and clones specific for HLA-A1 or HLA-B8 (residues 60-84) were generated
      from normal PBLs (A2,29 B62,- DR1,4 DQ3). Most clones were A1 specific (16 out of
      17 tested), HLA-DR4 restricted (8 out of 8), and lysed targets pulsed with A1
      peptide (16 out of 16). An amino acid substitution at position 86 of the DR4 beta
      chain (G -> V) abrogated the capacity of CD4+ CTLs to lyse target cells.
      Chloroquine treatment of A1-pulsed targets reduced their susceptibility to lysis,
      indicating a requirement for peptide processing. The TCL and clones were
      stimulated to proliferate by cells bearing intact HLA-A1 when autologous APCs
      were present, indicating that the epitope contained within the A1 60-84 peptide
      being recognized is produced when APCs process native HLA-A1. Furthermore, the
      clones and TCL did not recognize HLA-A1 on target cells carrying this allele plus
      self-HLA-DR4. These studies suggest a much wider role for CD4+ T cells in
      allograft immunity.

PMID- 9157084
TI  - Systemic lupus erythematosus with nephritis is strongly associated with the
      TNFB*2 homozygote in the Korean population.
AB  - To evaluate the association of TNFB NcoI polymorphism with SLE in the Korean
      population, we investigated the frequencies of the TNFB and HLADRB1 alleles in
      281 controls and 97 SLE patients, including 56 patients with nephritis and 41
      patients without nephritis. The frequency of the TNFB*2 homozygote in SLE was
      significantly increased over controls (43.3% vs 28.5%, RR = 1.9,p < 0.01). In SLE
      with nephritis, the TNFB*2 homozygote was more significantly increased (57.1% vs
      28.5%, RR = 3.4,p < 0.0001), whereas there was no significant difference between
      SLE without nephritis and controls. The study of HLA-DRB 1 alleles revealed the
      increased frequencies of DRB1*02 and *03 (30.9% vs 18.2%, RR = 2.0,p < 0.01; 8.2%
      vs 2.1%, RR = 4.1,p < 0.05). There was no significantly different distribution of
      HLA-DRB1 alleles between SLE patients with nephritis and without nephritis. We
      found positive LD between TNFB*1 and HLA-DR1B1*13, and between TNFB*2 and the
      particular DRB1 allele: *15, *04, and *07 in controls and/or in SLE patients.
      After stratification for each HLADRB1 allele, SLE with nephritis showed a higher
      frequency of TNFB*2 homozygote compared with the corresponding controls in
      DRB1*15, *08, and *09 positives. Our results suggest that the TNFB*2 homozygote
      may be a strong susceptibility gene of SLE with nephritis in the Korean
      population.

PMID- 9157085
TI  - Functional significance of varied quantitative and qualitative expression of HLA
      A2.1 antigens in determining the susceptibility of cells to cytotoxic T
      lymphocytes.
AB  - To determine whether varied quantitative HLA expression affects the
      susceptibility of target cells to CTLs, a panel of 15 EBV-transformed
      lymphoblastoid cell lines expressing a fivefold difference of surface HLA-A2.1
      antigens were employed. The susceptibility of these cell lines to HLA-A2.1
      restricted and influenza virus matrix peptide-specific CTLs was correlated with
      the amounts of HLA-A2.1 antigens expressed on their surface. The results show a
      linear correlation between both parameters using exogenous viral peptide. The
      same linear correlation was observed when target cells infected with influenza
      virus were studied. These findings support the hypothesis that the amount of HLA
      antigens expressed on the cell surface is functionally significant in determining
      the susceptibility of target cells to CTLs. During our study, we also found that
      two HLA-A-2.1-positive cell lines were unresponsive to the CTL. Further
      investigation of the amino acid sequences of these cell lines reveals that their
      HLA-A2.1 antigens belong to the HLA-A0207 subtype which is different from HLA
      A0201(A2.1) by one nucleotide. This difference results in an amino acid
      substitution from tyrosine to cysteine at position 99 of HLA-A2.1 heavy chains.
      Using a peptide-induced reconstitution assay, it was shown that failure of the
      peptide binding is responsible for the absence of cytotoxicity. This finding
      supports the hypothesis that amino acid 99 plays an important role in determining
      the peptide-binding specificity of HLA-A2 molecules.

PMID- 9157086
TI  - A computerized method to predict the discriminatory properties for class II
      sequencing based typing.
AB  - Accurate identification of alleles or groups of alleles is obtained using DNA
      techniques for HLA class II typing. In PCR-SSP and PCR-SSO the typing resolution
      is dependent on the location of the amplification primers and the number of
      oligonucleotide probes used for hybridization. These primers are developed based
      upon the known allele sequences. However, the number of published allele
      sequences increases rapidly. Periodic reconsideration of the discriminatory
      properties of the methods used is necessary and often leads to the addition of
      primers, and an increase of ambiguous genotypes. SBT is a high-resolution class
      II typing method which utilizes the second exon sequence at all positions for
      typing. Using a generic amplification and sequencing approach, a limited number
      of ambiguous heterozygotes can be expected. However, the number of ambiguities is
      dependent on the location of the primers. These ambiguities can be solved by the
      use of group-specific primers in either the amplification or sequencing reaction.
      To identify the applicability of a SBT approach with respect to typing
      resolution, it is important to identify these ambiguities and develop strategies
      to solve them. We developed software that predicts the ambiguous heterozygotes,
      and analyzes their sequences for group specific primers, solving these
      ambiguities. The location of the primers is considered as well as the use of
      generic vs group-specific amplification or sequencing reactions. Allele sequences
      of all class II genes, as accepted by the WHO nomenclature committee for factors
      of the HLA system and submitted to the EMBL/Genbank databases, are analyzed to
      define the allelic discrimination level of HLA-DQB1, -DQA1, -DFB1, -DPA1, -DRB1, 
      DRB3, -DRB4, and -DRB5.

PMID- 9157087
TI  - Polymorphism of HLA-DRB, -DQA1, and -DQB1 in rheumatoid arthritis in Asian
      Indians: association with DRB1*0405 and DRB1*1001.
AB  - We investigated the DRB, DQA1, and DQB 1 polymorphism and haplotypes in sporadic
      and familial RA subjects of Asian Indian origin by PCR oligotyping using
      biotinylated SSOPs. Molecular subtyping of DRB 1*04 in RA patients showed
      strongest association with highest relative risk with DRB 1*0405, followed by
      DRBI*0401. A significant decreased frequency of DRBI*1502 was observed in
      patients compared to controls (chi 2 = 4.5). Among other alleles, DRBI*1001 was
      found to be significantly increased. A total of 73.3% of patients carried the
      shared sequence of the third HVR (67-74) of DRB1 domain compared to its presence
      in only 37.6% of controls. A significant number of patients carried DR4
      haplotypes on DQBI*0302 (58%) as against DQBI*0301 which was present only on
      10.5% of the haplotypes. When compared to controls, the difference was
      significant for the latter allele only. Few unique DRDQ haplotypes were observed
      in Asian Indians. Among DR-DQ haplotypes, DRB1*0401-DQB1*0302 gave the highest
      risk whereas DRB1*0403-DQB1*O301 was negatively associated. Alleles with negative
      charge at position 70 confer protection or are negatively associated with RA
      whereas among the associated alleles, glycine at position 86 resulted in higher
      risk than those with valine at this position. A heterogenous association of DQB1
      alleles with DR4 subtypes, influencing susceptibility to RA, suggests the DQB
      locus is not primarily associated with RA and susceptibility lies in the sequence
      67-74 of the DRB1 loci.

PMID- 9157088
TI  - The role of HLA-DR-DR and HLA-DR-DP interactions in genetic susceptibility to
      rheumatoid arthritis.
AB  - In order to analyze the relationships between the DR and DP loci in the genetic
      susceptibility to RA, HLA-DRB1 and -DPB1 polymorphism was studied in 155 RA
      patients compared to 150 controls, using a reverse dot-blot analysis. Our data
      were consistent with the involvement of the amino acid in position 71 of the
      third hypervariable region of the DR beta 1 chain in susceptibility to the
      disease. The higher risk for RA was observed in patients who carried the
      association of a lysine (K), characterizing the DRB1* 0401 susceptibility allele,
      with an arginine (R), observed in all the other DRB1* susceptibility alleles
      (21.9% vs 0.6%, p(c) < 10(-6), OR = 42) In the absence of arginine, the presence
      of lysine was still associated with the disease (33% vs 19%, p(c) < 0.03, OR =
      2). In contrast, in the absence of lysine, the frequency of arginine in position
      71 was similar in patients and controls (30% vs 26%, p = NS). On another hand,
      the analysis of the HLA-DPB1 locus showed that the DPB1 *0401 allele frequency
      was significantly increased in the RA patient group (n = 47) who expressed only
      arginine at the position 71 of the beta 1 chain (82% vs 56% in controls, p <
      0.008), with role of HLA-DR--DR and -DR-DP interactions in the genetic
      susceptibility to RA.

PMID- 9157089
TI  - An association in non-insulin-dependent diabetes mellitus subjects between
      susceptibility to retinopathy and tumor necrosis factor polymorphism.
AB  - In IDDM an association between diabetic retinopathy and polymorphic markers of
      MHC has been described. However, these associations are complicated by a primary
      association between the MHC and IDDM. Because the pathogenesis of retinopathy is
      likely to be the same in IDDM and NIDDM, NIDDM subjects with retinopathy would be
      the ideal population to study for an association with MHC markers. The following
      South Indian subjects were therefore studied: unselected NIDDM (n = 76),
      unselected IDDM (n = 99), non-diabetic controls (n = 96), NIDDM subjects with
      maculopathy (MAC), n = 55, NIDDM subjects with proliferative retinopathy (PR), n
      = 53, and without retinopathy (LTD), n = 46. DNA was amplified and studied using
      a microsatellite polymorphism located 3.5 kb upstream of TNF-beta within the MHC
      class III region on the short arm of chromosome 6. No differences in allelic
      distribution were observed between the random NIDDM subjects and controls (p =
      0.17). Differences in allelic distribution were found between unselected IDDM and
      controls (P = 0.016) and between the NIDDM subjects with maculopathy and/or
      proliferative retinopathy and no retinopathy (P = 0.006). This association could
      be accounted for by those patients with proliferative retinopathy (MAC vs LTD, p
      = 0.23; MAC vs PR, p = 0.07; and PR vs LTD, p = 0.002).

PMID- 9157090
TI  - A novel DR beta 1*03 allele identified by polymerase chain reaction-restriction
      fragment length polymorphism.
AB  - This report describes a new MHC class II allele, HLA-DR beta 1*0306, discovered
      in a 31-year-old Norwegian male. The allele typed serologically as DRw52 (DR3)
      and amplified in PCR using DR52-associated group primers. This product could not
      be identified using established restriction digests, however. Use of Asp 700, Msp
      I, Hha I, Bse RI, Mnl I, Hph I, and Bsrb I gave banding patterns expected for a
      DR beta 1*03011 allele, but Rsa I had an additional site at codon 47. Sequencing
      showed a single base change at this position, with the substitution of tyrosine
      for phenylanine in this new allele. The biologic impact of this substitution
      remains to be determined.

PMID- 9157091
TI  - Three HLA-DMB variants in Korean patients with autoimmune diseases.

PMID- 9157092
TI  - Two newly discovered alleles of major histocompatibility complex-encoded LMP7 in
      Korean populations.

PMID- 9157093
TI  - Sequence of HLA-DRB 1*1606 is incorrect.

PMID- 9157094
TI  - Nomenclature for factors of the HLA system, update January 1996. The Who
      Nomenclature Committee for Factors of the HLA System.

PMID- 9157095
TI  - Effects of reinforcer quality on behavioral momentum: coordinated applied and
      basic research.
AB  - The high-probability (high-p) instructional sequence has been an effective
      treatment for noncompliance. However, treatment failures have also been reported.
      We hypothesized that the efficacy of the high-p treatment may be improved by
      using higher quality reinforcers for compliance to high-p instructions. The
      resistance of compliance to change was tested by varying reinforcer quality in
      two applied studies and a basic laboratory experiment. Experiment 1 tested the
      hypothesis that an increase in reinforcer quality for high-p compliance will
      increase the effectiveness of the high-p treatment when it fails to increase
      compliance. Experiment 2 assessed the effects of reinforcer quality on resistance
      of compliance to change by presenting successive low-p requests following the
      high-p treatment. A basic laboratory study (Experiment 3) was conducted to
      further isolate the relation between reinforcer quality and behavioral momentum.
      Two different liquid reinforcers (sucrose and citric acid solutions) were
      presented in a two-component multiple variable-interval variable-interval
      schedule followed by a single extinction test session. Results of all three
      experiments showed a generally consistent relationship between reinforcer quality
      and behavioral momentum.

PMID- 9157096
TI  - A preliminary analysis of interactive effects between common classroom
      contingencies and methylphenidate.
AB  - To assess the drug-behavior interaction effects with an 8-year-old boy wih
      attention deficit hyperactivity disorder, common classroom antecedent (e.g.,
      seating arrangement) and consequent (e.g., peer prompts) stimuli were alternated
      within a school day while drug conditions (methylphenidate vs. placebo) were
      alternated across days. The results suggested that peer attention maintained
      disruptive behavior when methylphenidate was absent but not when it was present.

PMID- 9157097
TI  - Negative side effects of noncontingent reinforcement.
AB  - Noncontingent reinforcement (NCR) has emerged as a treatment package for severe
      behavior problems. Although concerns about potential side effects (such as
      incidental reinforcement) have been raised, there have been few reported negative
      side effects in published studies to date. In this article, we report an NCR
      treatment evaluation for severe aggression that produced (a) an extinction burst
      and (b) incidental reinforcement. These side effects were evaluated by examining
      within-session response patterns and response distributions. As a solution, a
      brief omission contingency was added to the reinforcement schedule. The omission
      contingency resulted in decreased aggression rates.

PMID- 9157098
TI  - A rapid method for evaluating the necessity for both a behavioral intervention
      and methylphenidate.

PMID- 9157099
TI  - Teaching receptive naming of Chinese characters to children with autism by
      incorporating echolalia.
AB  - The facilitative effect of incorporating echolalia on teaching receptive naming
      of Chinese characters to children with autism was assessed. In Experiment 1,
      echoing the requested character name prior to the receptive naming task
      facilitated matching a character to its name. In addition, task performance was
      consistently maintained only when echolalia preceded the receptive manual
      response. Positive results from generalization tests suggested that learned
      responses occurred across various novel conditions. In Experiment 2, we examined
      the relation between task difficulty and speed of acquisition. All 3 participants
      achieved 100% correct responding in training, but learning less discriminable
      characters took more trials than learning more discriminable characters. These
      results provide support for incorporating echolalia as an educational tool within
      language instruction for some children with autism.

PMID- 9157100
TI  - Does functional communication training compete with ongoing contingencies of
      reinforcement? An analysis during response acquisition and maintenance.
AB  - We examined the effectiveness of functional communication training (FCT) in
      reducing self-injurious behavior (SIB) and in shaping an alternative
      (communicative) response while SIB continued to be reinforced. Following a
      functional analysis of 3 individuals' SIB, we attempted to teach an alternative
      response consisting of a manual sign to each individual, using the reinforcer
      that maintained SIB. When FCT was implemented without extinction. SIB remained at
      baseline rates for all participants, and none of the participants acquired the
      alternative response. When extinction was added to the training procedure, SIB
      decreased and manual signing increased for all participants. To determine if
      signing, when established, would compete with SIB when both were reinforced,
      extinction was then withdrawn. Signing was maintained and SIB occurred at low
      rates for 2 individuals, but SIB returned to baseline rates for the 3rd
      individual, necessitating the reimplementation of extinction. These results
      suggest that it may be difficult to establish alternative behaviors if
      inappropriate behavior continues to be reinforced, but that, when established,
      alternative behavior might compete successfully with ongoing contingencies of
      reinforcement for inappropriate behavior.

PMID- 9157101
TI  - GA strategy for variable selection in QSAR studies: GA-based PLS analysis of
      calcium channel antagonists.
AB  - The GAPLS (GA based PLS) program has been developed for variable selection in
      QSAR studies. The modified GA was employed to obtain a PLS model with high
      internal predictivity using a small number of variables. In order to show the
      performance of GAPLS for variable selection, the program was applied to the
      inhibitor activity of calcium channel antagonists. As a result, variables largely
      contributing to the inhibitory activity could be selected, and the structural
      requirements for the inhibitory activity could be estimated in an effective
      manner.

PMID- 9157102
TI  - META. 3. A genetic algorithm for metabolic transform priorities optimization.
AB  - META is a knowledge-based expert system that simulates the biotransformation of
      xenobiotics. It operates with the help of a dictionary (knowledge base) to seek
      target fragments in a compound and transform them to products. Here, a genetic
      algorithm is introduced to help build the knowledge base and optimize the
      performance of the methodology.

PMID- 9157103
TI  - Effect of head-centered and body-centered hemispace in unilateral neglect.
AB  - The aim of this study was to evaluate the effects of head-centered and body
      centered hemispace on a line bisection task in patients with left unilateral
      neglect. Five patients with left unilateral neglect were given a line bisection
      task under four different conditions. The results clearly demonstrate that both
      head-centered and body-centered hemispace had a statistically significant effect
      on the line bisection task. The results are discussed with respect to a reference
      frame of space and the validity of dividing unilateral neglect into two
      components (i.e., spatial neglect and object neglect) is proposed.

PMID- 9157104
TI  - MRI and nonverbal cognitive deficits in children with neurofibromatosis 1.
AB  - Magnetic resonance imaging brain scans and neuropsychological assessments of 17
      children who met the NIH consensus diagnostic criteria for neurofibromatosis Type
      1 were carried out in order to determine if there is a relationship between
      presence of high intensity signal abnormalities on MRI scans and nonverbal
      cognitive deficits. Cranial MRI scans in 10 patients (58.8%) demonstrated high
      intensity signal abnormalities, most frequently in the cerebral peduncles.
      Fifteen patients had nonverbal cognitive deficits (88.2%), including difficulty
      judging the orientation of lines, matching complex visual stimulus
      configurations, recalling pictures of faces, as well as copying and drawing from
      memory a complex geometric figure. There was not a significant association
      between nonverbal neuropsychological deficits and presence of high intensity
      signal abnormalities on MRI scans, possibly because the location of these
      hyperintense abnormalities was typically below the level of the basal ganglia.
      These findings suggest that the high intensity signal lesions seen on the MRI
      scans of children with neurofibromatosis Type 1 do not predict or explain their
      nonverbal cognitive deficits.

PMID- 9157105
TI  - Impaired set-shifting in Parkinson's disease: new evidence from a lexical
      decision task.
AB  - On a lexical decision (LD) task, participants quickly decide whether a target
      letter string is a word. When a target word (e.g., CARROT) is preceded by a
      category cue (e.g., VEGETABLE), participants respond more quickly than when the
      target is preceded by a semantically neutral cue (e.g., BLANK). Previously,
      Spicer, Brown, and Gorell (1994) reported that patients with PD, when tested with
      a variation of Neely's (1977) LD task, showed hyperpriming. That is, patients
      with PD exhibited a larger difference in reaction time between the neutral cue
      and category prime conditions than did controls. The present study found little
      evidence that PD hyperpriming was explained by difficulties accessing semantic
      information. Rather, hyperpriming appeared to be related to a general tendency
      among a subgroup of patients with PD to perseverate.

PMID- 9157106
TI  - Word-list generation deficits in dementia.
AB  - To evaluate the specificity of the semantic fluency deficit in Alzheimer's
      disease (AD), we compared the performances of patients with AD, Huntington's
      disease (HD), vascular dementia (VD), and healthy control subjects on tasks of
      category (i.e., semantic) and first-letter (i.e., phonemic/lexical) word list
      generation. As compared to age-appropriate controls, all three patient groups
      demonstrated relatively more impaired semantic than phonemic fluency. Dementia
      severity did not affect this relationship. Thus, the greater vulnerability of
      semantically guided fluency is not specific to AD but occurs in other dementias
      as well. Deficits in both the organization of semantic memory and retrieval from
      long-term storage appear to contribute to the relatively poorer performance on
      semantic than phonemic fluency tasks observed in patients with AD, VD, and HD.

PMID- 9157107
TI  - Handedness and performance variability as factors influencing mirror movement
      occurrence.
AB  - A finger flexion task was used to investigate the effect of hand preference and
      performance variability on intensity of mirror movement. Right- and left-handed
      subjects were asked to maintain target forces, with either their index or small
      finger, that represented 25, 50, or 75% of their maximum strength capacity for
      the active finger. Greater mirror movement occurred when the small finger was
      active, and where there was greater variability in task performance, while mirror
      movement intensity was less when the dominant hand and the index finger were
      active. These findings were consistent with the cortical activation explanation
      of motor overflow (Todor & Lazarus, 1986a), and suggest that task variability is
      an important factor influencing motor overflow production. It was concluded that,
      if performance variability reflects the efficiency of cortical activation
      underlying control of a voluntary task, then refined cortical control decreases
      the potential for motor overflow to occur. However, it is necessary to clarify
      the relationship between hand preference, performance variability, and motor
      overflow, perhaps by examining the neural pathways involved in motor overflow
      production.

PMID- 9157108
TI  - Verbal learning subtypes in traumatic brain injury: a replication.
AB  - Traumatic brain injury (TBI) has been associated with memory impairments, but the
      severity and qualitative aspects of such impairment do not appear homogeneous
      across patients. This study sought to replicate an earlier investigation that
      found distinct verbal learning subtypes in TBI using the California Verbal
      Learning Test (CVLT). CVLT data from 88 acute rehabilitation inpatients with
      mild, moderate, and severe traumatic brain injuries were analyzed with multiple
      cluster analytic techniques. Cluster analyses yielded five learning subtypes,
      three of which appeared similar to the subtypes previously identified as Active,
      Disorganized, and Passive subtypes, and two that appeared similar to the
      Deficient subgroup. Traumatic brain injury appears to be characterized by
      heterogeneous, but fairly reliable, verbal learning subtypes that can be detected
      early postinjury.

PMID- 9157109
TI  - Computerized assessment of sustained attention: a review of factors affecting
      vigilance performance.
AB  - Results of empirical studies using computerized tests of sustained attention are
      summarized. Factors that affect vigilance performance fall into three broad
      categories: task parameters, environmental or situational factors, and subject
      characteristics. Complex interactions of factors from each category affect
      performance further. Such interactions may help to explain inconsistencies in the
      literature regarding effects on vigilance. Implications for both research and
      clinical practice are discussed.

PMID- 9157110
TI  - Computerized assessment of sustained attention: interactive effects of task
      demand, noise, and anxiety.
AB  - In a sample of 163 college undergraduates, the effects of task demand, noise, and
      anxiety on Continuous Performance Test (CPT) errors were evaluated with multiple
      regression and multivariate analysis of variance. Results indicated significantly
      more omission errors on the difficult task. Complex interaction effects of noise
      and self-reported anxiety yielded more omissions in quiet intermittent white
      noise, particularly for high-anxious subjects performing the difficult task.
      Anxiety levels tended to increase from pretest to posttest, particularly for low
      anxious subjects in the quiet, difficult-task condition, while a decrease was
      seen for high-anxious subjects in the loud, easy-task condition. Commission
      errors were unrelated to any predictor variables, suggesting that "attention"
      cannot be considered a unitary phenomenon. The variety of direct and interactive
      effects on vigilance performance underscore the need for clinicians to use a
      variety of measures to assess attentional skills, to avoid diagnosis of attention
      deficits on the basis of a single computerized task performance, and to rule out
      anxiety and other contributors to poor vigilance task performance.

PMID- 9157111
TI  - Longitudinal examination of American National Adult Reading Test (AMNART)
      performance in dementia of the Alzheimer type (DAT): validation and correction
      based on degree of cognitive decline.
AB  - The American National Adult Reading Test (AMNART) was constructed to provide a
      valid and stable estimate of premorbid verbal IQ (VIQ) in dementing individuals.
      However, recent studies have brought into question its validity in patients with
      dementia of the Alzheimer type (DAT). The present study was designed to
      longitudinally assess the validity of the AMNART in 40 DAT patients and 40
      demographically matched normal control (NC) subjects. The results showed that VIQ
      estimates for patients with DAT were significantly lower than those of NC
      subjects and declined significantly over time with increasing dementia severity
      as measured by the Mini-Mental State Examination (MMSE) and the Dementia Rating
      Scale (DRS). An MMSE-based correction factor was derived for the DAT group which
      allows for the effective estimation of premorbid VIQ in these patients.

PMID- 9157113
TI  - Short-form alternatives to the Judgment of Line Orientation Test.
AB  - The Judgment of Line Orientation Test (JLO; Benton, Hamsher, Varney, & Spreen,
      1983) is frequently used as a motor-free method of evaluating visuospatial
      processing but can be time-consuming to administer. We investigated the internal
      consistency, validity, and utility of two parallel JLO short forms in a mixed
      clinical sample of 386 patients. Mean scores were equivalent, and correlational
      analyses supported the internal consistency and validity of both short forms.
      When compared to the standard JLO, the odd- and even-item short forms
      demonstrated good sensitivity, specificity, overall hit rate and predicted
      positive and negative accuracy. We conclude that the JLO short forms possess
      sufficient internal consistency, validity, and utility for serial assessment in
      research studies. The JLO short forms may potentially be used in clinical
      screening situations by applying a single cut-off score to differentiate levels
      of performance. However, more detailed clinical use of these JLO short forms will
      necessitate collection of normative data in order to generate accurate percentile
      rankings.

PMID- 9157112
TI  - Utility of a Wisconsin Card Sorting Test short form in persons with Alzheimer's
      and Parkinson's disease.
AB  - The utility of administering only the first deck of 64 cards from the Wisconsin
      Card Sorting Test (WCST-64) in persons with Alzheimer's (AD) and Parkinson's
      disease (PD) was evaluated. There were 35 elderly subjects matched for gender,
      age, and education in each of four groups: controls, PD without dementia (PDN),
      PD with dementia (PDD), and AD. Additionally, the control and PDN subjects were
      matched for level of cognitive functioning as were the PDD and AD groups. Results
      revealed that demented persons performed significantly worse than nondemented
      subjects. The WCST-64 was also sensitive to the subtle executive deficits
      demonstrated by persons with PD without dementia. The findings support the use of
      the WCST-64 in elderly persons with AD and PD.

PMID- 9157114
TI  - Handedness and its association with gender-related psychological and
      physiological characteristics.
AB  - Prenatal exposure to a high level of testosterone is thought to result in
      sinistrality and increased masculinization in females. This paper seeks to
      determine whether sinistral females show more masculine characteristics relative
      to dextral females. Demonstration of such a relationship would support the
      proposition that testosterone affects laterality. Masculine and feminine
      personality characteristics, breast size, age at menarche, and regularity of
      menstruation were measured via a questionnaire administered to 40 dextral and 40
      sinistral female university students. Sinistrals were found to score
      significantly higher on the masculine subscale and lower on the feminine subscale
      of the Bem Sex Role Inventory relative to their dextral counterparts. No
      differences were found between the groups for breast size, menstrual regularity,
      or age at menarche. These results demonstrate that hand preference is associated
      with gender-related psychological characteristics, but not the physiological
      characteristics measured. Thus, the possibility that the different sex roles
      adopted by sinistrals and dextrals is the result of socialisation rather than
      biological mechanisms, such as testosterone, cannot be ruled out.

PMID- 9157115
TI  - Victoria Symptom Validity Test: efficiency for detecting feigned memory
      impairment and relationship to neuropsychological tests and MMPI-2 validity
      scales.
AB  - Error scores and response times from a computer-administered, forced-choice
      recognition test of symptom validity were evaluated for efficiency in detecting
      feigned memory deficits. Participants included controls (n = 95), experimental
      malingerers (n = 43), compensation-seeking patients (n = 206), and patients not
      seeking financial compensation (n = 32). Adopting a three-level cut-score system
      that classified participant performance as malingered, questionable, or valid
      greatly improved sensitivity with relatively little impact on specificity. For
      error scores, convergent validity was found to be adequate and divergent validity
      was found to be excellent. Although response times showed promise for assisting
      in the detection of feigned impairment, divergent and convergent validity were
      weaker, suggesting somewhat less utility than error scores.

PMID- 9157116
TI  - Performance consistency in picture naming: a study of the rehabilitation effect
      on two aphasic patients.
AB  - We describe the effect of language rehabilitation on the naming deficits of 2
      patients affected by longstanding amnestic aphasia. In particular, our aim was to
      study the evolution of the rate of inconsistent naming (i.e., performance with
      stimuli that were named sometimes correctly and sometimes incorrectly when the
      test was repeated at close intervals) by means of a stochastic model based on
      Markov chains (Faglioni & Botti, 1993). From a quantitative point of view, both
      patients showed a significant improvement that was still present several months
      after treatment. However, at baseline these patients showed different degrees of
      consistency which revealed a basic difference in the way their language
      functions. One case presented with low consistency, delayed responses, and self
      corrections: A clear effect of rehabilitation was improvement in consistency and
      reduction of delays. In the other case, at baseline consistency was greater, but
      naming of pictures did not improve even after delay or self-correction; after
      rehabilitation more stimuli were named correctly, but only after delay and self
      correction. The relevance of consistency and its relationship with delayed naming
      and self-corrections is discussed. It is suggested that consistency analysis
      based on stochastic models would make a useful contribution to the description
      and interpretation of naming deficits in aphasic patients.

PMID- 9157117
TI  - Use of nucleic acid probes to identify mycobacteria directly from Difco ESP-Myco
      bottles.
AB  - Mycobacterial isolates were identified directly from positive ESP-Myco bottles by
      use of nucleic acid probes. Retrospective analysis of 360 cultures which grew
      either Mycobacterium tuberculosis, M. avium complex, or M. gordonae showed that
      87% were identified by direct testing of an aliquot obtained at the time a
      positive culture was detected. Another 12% of these cultures gave results in the
      equivocal range, with only 1% of the isolates yielding negative results on
      initial testing.

PMID- 9157118
TI  - An Ehrlichia strain from a llama (Lama glama) and Llama-associated ticks (Ixodes
      pacificus).
AB  - An ehrlichia was identified in the blood of a diseased llama (lama glama).
      Sequencing of its 16S rRNA gene showed the ehrlichia to be closely related to
      members of the Ehrlichia phagocytophila genogroup. The agent was also found in a
      pool of ticks (Ixodes pacificus) collected at the llama site.

PMID- 9157119
TI  - A nosocomial outbreak due to Enterobacter cloacae strains with the E. hormaechei
      genotype in patients treated with fluoroquinolones.
AB  - During a 7-month period, we isolated 21 highly fluoroquinolone-resistant
      Enterobacter cloaecae strains in units from two hospitals in Marseille, France.
      Random amplification of polymorphic DNA showed clonal identity between isolates
      which, furthermore, presented the Enterobacter hormaechei genotype on DNA-DNA
      hybridization. The emergence of this clone was observed only in patients treated
      with fluoroquinolones.

PMID- 9157120
TI  - Fatal sepsis caused by Corynebacterium amycolatum in a premature infant.
AB  - Corynebacterium amycolatum has not been reported as a cause of human infections
      up to now, but usually the bacterium is misidentified in clinical specimens as
      Corynebacterium xerosis. We report the first case of neonatal sepsis due to
      Corynebacterium amycolatum with a fatal outcome in a premature infant.

PMID- 9157121
TI  - Impact of the human immunodeficiency virus epidemic on detection of Mycobacterium
      isolates in a general hospital.
AB  - The number of human samples processed in our mycobacteriology laboratory ranged
      from 148 per 1,000 admissions in 1988 to 263 per 1,000 admissions in 1995 (5.2%
      were positive). The human immunodeficiency virus (HIV)-positive population
      contributed 33.3% of all samples, 43.3% of all isolates, and 36% of all new
      patients. Given that the ratios of the total number of samples to the number of
      Mycobacterium-positive samples were 18.3:1 in HIV-positive patients and 28:1 in
      HIV-negative patients, efforts to reduce the laboratory workload should begin
      with the HIV-negative population.

PMID- 9157122
TI  - Detection of motility and putative synthesis of flagellar proteins in Salmonella
      pullorum cultures.
AB  - Salmonella pullorum is a host-adapted pathogen of poultry previously thought to
      be nonmotile and nonflagellated. We discovered that motility can be induced in
      this organism under special medium conditions, and this motility was observed in
      39 of 44 S. pullorum isolates tested. The migration appeared to occur only on the
      medium surface and not within the medium itself, indicating that swimming may not
      be responsible for this event. Agar concentration, carbohydrate concentration and
      type, and temperature of incubation all affected the motility. Flagellar stains
      and transmission electron micrographs of the motile S. pullorum culture showed
      long fibrous appendages resembling flagella extending from the cells, but these
      appendages were thinner and less numerous than the flagella observed on
      Salmonella enteritidis. Antisera to G flagellar antigens reacted strongly with
      the induced-motility S. pullorum culture, indicating that G epitopes were
      expressed on these cells. These results indicate that, contrary to the paradigm
      which held that S. pullorum is nonmotile and nonflagellated, motility can be
      induced in S. pullorum and that the organism appears to have the capacity to
      produce flagella.

PMID- 9157123
TI  - Comparison of Etest and agar dilution method for antimicrobial susceptibility
      testing of Flavobacterium isolates.
AB  - The Etest was evaluated as a possible alternative to the standard agar dilution
      method for susceptibility testing of nine antimicrobial agents against
      Flavobacterium species. In studies of 100 clinical isolates, the agreement
      between the MICs (+/-1 log2 dilution) obtained by the two methods was acceptable
      for cefotaxime, ceftazidime, amikacin, minocycline, ofloxacin, and ciprofloxacin
      (> 90%). Conversely, the agreement between the results obtained for piperacillin
      was limited (84%). The overall agreement was 92.5%.

PMID- 9157124
TI  - Isolation of Lautropia mirabilis from sputa of a cystic fibrosis patient.
AB  - An aggregate-forming coccus, isolated twice as the predominant microorganism in
      sputa from a cystic fibrosis patient on consecutive days, was shown to belong to
      the species Lautropia mirabilis on the bases of similarities of 16S rRNA gene
      sequences and phenotype. These isolates of L. mirabilis appear to be the first
      reported from a patient with cystic fibrosis and outside of Denmark.

PMID- 9157125
TI  - Effect of zinc concentration in Mueller-Hinton agar on susceptibility of
      Pseudomonas aeruginosa to imipenem.
AB  - The susceptibility of Pseudomonas aeruginosa to imipenem has been shown to vary
      according to zinc concentration in the media. MICs of imipenem for 68 unique
      clinical isolates of P. aeruginosa were determined in media supplemented with
      zinc at concentrations between 0.5 and 6.0 micrograms/ml. In agar containing up
      to 3 micrograms of zinc/ml, 75 to 82% of the strains were susceptible to imipenem
      at an MIC of < or = 4 micrograms/ml. In agar supplemented to contain 6 micrograms
      of zinc/ml, however, only 40% of the strains were susceptible to imipenem.
      Manufacturers should ensure that the concentration of zinc in commercial media is
      below 3 micrograms/ml to avoid false classification of isolates as resistant to
      imipenem.

PMID- 9157126
TI  - The diagnostic yield of acid-fast-bacillus smear-positive sputum specimens.
AB  - The yield of mycobacterial culture from acid-fast-bacillus smear-positive sputum
      specimens was 387 or 439 (88.2%). Forty-nine of 52 culture-negative specimens
      came from patients on treatment. We conclude that the yield of culture from smear
      positive sputum specimens is very high and that only two acid-fast-bacillus smear
      positive specimens are needed for the initial evaluation of pulmonary
      mycobacteriosis.

PMID- 9157127
TI  - Kidney and liver transplants from a donor infected with Naegleria fowleri.
AB  - We describe the first reported case of organ transplantation from a boy who had
      died of undiagnosed Naegleria fowleri infection. While no subsequent amebic
      infections occurred in the three organ recipients, our report illustrates the
      need for an improved strategy for evaluating the benefits and risks of
      transplanting tissues from persons whose illness was likely caused by an
      infectious agent.

PMID- 9157128
TI  - Use of enzyme-linked immunosorbent assay techniques with cross-reacting human
      sera in diagnosis of murine typhus and spotted fever.
AB  - Enzyme-linked immunosorbent assay (ELISA) techniques for the determination of
      immunoglobulin G to rickettsial lipopolysaccharides were developed. These
      techniques provide a simple and convenient way to serodiagnose Mediterranean
      spotted fever and murine typhus with a single serum dilution. The results of the
      ELISAs correlated with the indirect immunofluorescence assay titers of cross
      reacting sera.

PMID- 9157129
TI  - Species differentiation by internally transcribed spacer PCR and HhaI digestion
      of fluconazole-resistant Candida krusei, Candida inconspicua, and Candida
      norvegensis strains.
AB  - PCR amplification of the regions containing the internally transcribed spacers
      and 5.8S rRNA gene of Candida krusei, C. inconspicua, and C. norvegensis yielded
      fragments of 510, 460, and 500 bp, respectively. HhaI digestion of these
      fragments yielded species-specific bands. Random amplification of polymorphic DNA
      with primer R108 showed interspecific discriminatory band patterns.
      Susceptibilities to fluconazole and amphotericin B were determined.

PMID- 9157130
TI  - Human immunodeficiency virus (HIV) RNA quantitation using the Amplicor HIV-1
      Monitor test: not all yellow-top tubes are suitable for blood collection.

PMID- 9157131
TI  - Turnaround times for mycobacterial cultures.

PMID- 9157132
TI  - Microtiter virus isolation and enzyme immunoassays for detection of bovine viral
      diarrhea virus in cattle serum.
AB  - Cattle immunotolerant to and persistently infected (PI) with bovine viral
      diarrhea (BVD) virus (BVDV) constitute the mechanism by which BVDV persists in
      cattle herds. Two procedures for using serum to detect PI cattle were developed
      and evaluated. BVDV was found to remain viable for 7 days in serum samples stored
      at room temperature. The tests use cell culture virus isolation (VI) in 96-well
      microtiter plates, followed by immunostaining of cell monolayers with monoclonal
      antibodies. One technique, the immunoperoxidase monolayer assay (IPMA), forms a
      red intracellular precipitate while the other, the monolayer enzyme-linked
      immunosorbent assay (M-ELISA) produces a yellow color in solution. The optimal
      incubation period for microtiter VI was determined to be 4 days. Optimal IPMA
      staining was obtained by fixing cell monolayers with 20 to 30% acetone, whereas a
      simple dry-rehydrate-dry cycle provided optimal M-ELISA staining. The M-ELISA and
      IPMA had the same sensitivities and specificities, but the M-ELISA was a more
      rapid procedure and use of a spectrophotometer for reading samples allowed for
      greater objectivity. When compared to standard VI with routine samples submitted
      for the diagnosis of BVD, M-ELISA and IPMA had a relative sensitivity of 85% and
      a relatively specificity of 100%. When only samples from cattle suspected of
      being PI were considered, these two parameters were 100% for both IPMA and M
      ELISA. The two procedures, especially the M-ELISA, are suitable for whole-herd
      testing to identify PI cattle. The appeal of these tests is derived from the
      convenience of using serum as a diagnostic sample and the ability to rapidly
      screen large numbers of samples at low cost.

PMID- 9157133
TI  - Identification and characterization of a novel DNA marker associated with
      epidemic Burkholderia cepacia strains recovered from patients with cystic
      fibrosis.
AB  - Burkholderia cepacia is a problematic pathogen that may spread among patients
      with cystic fibrosis (CF). One highly infectious CF strain that causes epidemics
      in both the United Kingdom and eastern Canada has been shown to possess both the
      cable pilin subunit gene (cblA) and a unique combination of insertion sequences.
      However, no genetic markers linking this strain type with other types epidemic at
      various centers have been identified. Using a randomly amplified polymorphic DNA
      (RAPD) typing scheme, we identified an apparently conserved 1.4-kb fragment in
      the DNA fingerprint of epidemic B. cepacia strains. Conservation of the DNA
      marker among epidemic strains was demonstrated by Southern hybridization, and its
      prevalence was assessed in a collection of chromosomal DNAs extracted from 627
      isolates representative of 132 RAPD-defined B. cepacia strain types. The marker
      was specifically associated with seven epidemic CF strains, was absent among
      nonepidemic strains infecting individual patients with CF, and rare among strains
      recovered from the natural environment. Only one of the seven epidemic CF strain
      types possessed DNA homologous to cblA. The RAPD marker was designated the "B.
      cepacia epidemic strain marker" (BCESM). Sequence analysis of chromosomal DNA
      corresponding to the 1.4-kb RAPD marker revealed the presence of a putative open
      reading frame (ORF) with significant homology to several negative transcriptional
      regulators; the ORF was designated the "epidemic strain marker regulator," or
      esmR. The BCESM DNA is the first genetic marker that has been identified to be
      specifically associated with and conserved among several epidemic B. cepacia
      strains which infect multiple patients with CF.

PMID- 9157134
TI  - Rapid identification of clinically significant species and taxa of aerobic
      actinomycetes, including Actinomadura, Gordona, Nocardia, Rhodococcus,
      Streptomyces, and Tsukamurella isolates, by DNA amplification and restriction
      endonuclease analysis.
AB  - A previously described PCR-restriction fragment length polymorphism (RFLP)
      identification schema for Nocardia that used an amplified 439-bp segment
      (amplicon) of the 65-kDa heat shock protein gene was evaluated for potential use
      with isolates of all clinically significant aerobic actinomycetes. The study
      included 28 reference (American Type Culture Collection) strains and 198 clinical
      isolates belonging to 20 taxonomic groups. Of these 198 isolates, 188 could be
      differentiated by this PCR-RFLP method. Amplicons from all aerobic actinomycete
      isolates lacked BstEII recognition sites, thereby distinguishing them from those
      of mycobacteria that contain one or more such sites. Of 29 restriction
      endonucleases, MspI plus HinfI produced RFLP patterns that differentiated 16 of
      the 20 taxa. A single RFLP pattern was observed for 15 of 20 taxa that included
      65% of phenotypically clustered isolates. Multiple patterns were seen with
      Gordona bronchialis, Nocardia asteroides complex type VI, Nocardia
      otitidiscaviarum, Nocardia transvalensis, and Streptomyces spp. Streptomyces RFLP
      patterns were the most heterogeneous (five patterns among 19 isolates), but
      exhibited a unique HinfI fragment of > 320 bp. RFLP patterns that matched those
      from type strains of Streptomyces albus, Streptomyces griseus, or Streptomyces
      somaliensis were obtained from 14 of 19 Streptomyces isolates. Only 10 of 28
      isolates of N. otitidiscaviarum failed to yield satisfactory amplicons, while
      only 6 of 188 (3.2%) clinical isolates exhibited patterns that failed to match
      one of the 21 defined RFLP patterns. These studies extended the feasibility of
      using PCR-RFLP analysis as a rapid method for the identification of all
      clinically significant species and taxa of aerobic actinomycetes.

PMID- 9157135
TI  - Western immunoblot analysis of Haemobartonella muris and comparison of 16S rRNA
      gene sequences of H. muris, H. felis, and Eperythrozoon suis.
AB  - Infectious agents were isolated from the spleens of three wild mice (Apodemus
      argenteus) by intraperitoneal inoculation of the spleen homogenate into
      laboratory mice. The laboratory mice developed clinical signs and splenomegaly,
      and three isolates were maintained by passage in mice. Tetracyclines were
      effective in preventing infection of mice with these agents, but streptomycin and
      penicillin were ineffective. The agents did not grow in bacterial growth media or
      chicken embryos. In smears of blood from infected mice stained by the Giemsa or
      the indirect immunofluorescence method, numerous organisms were found on the
      surfaces of erythrocytes. Electron microscopy revealed cell wall-less pleomorphic
      cocci of 350 to 700 nm in diameter. On the basis of these results, the isolates
      were identified as Haemobartonella muris. There was no antigenic cross-reactivity
      with Rickettsia or Ehrlichia spp. or other related organisms. Western immunoblot
      analysis of three strains of H. muris with mouse antisera to H. muris revealed
      identical major antigens of 118, 65, 53, 45, and 40 kDa. By heteroduplex analysis
      of the three PCR-amplified segments of the 16S rRNA genes, the three strains of
      H. muris were found to be identical. The 16S rRNA genes of one of the H. muris
      strains, four strains of H. felis, and two strains of Eperythrozoon suis were
      sequenced and compared. The sequences of two strains of H. felis from cats in
      California were identical, as were the sequences of a strain from a cat in Ohio
      and a strain from a cat in Florida, but the similarity of sequences between the
      California and the Ohio-Florida strains was only 85%. The sequence of an H. muris
      strain was unique and was more closely related to that of the Ohio-Florida strain
      of H. felis (89%) than to that of the California strain of H. felis (84%). The
      sequence of E. suis from a pig in Illinois was identical to that from another pig
      from Taiwan. The similarity of the 16S rRNA gene sequence of E. suis with those
      of three Haemobartonella strains was 84 to 92%, with that of E. suis being most
      similar to that of the H. felis strain from California. In the phylogenetic
      analysis based on 16S rRNA gene sequences, the Haemobartonella spp. and E. suis
      formed a distinct clade more closely related to Mycoplasma spp. (79 to 83%
      similarity) than to Anaplasma marginale (72 to 75% similarity). Our results
      suggest that the Haemobartonella spp. and E. suis may be reclassified in the same
      genus in the family Mycoplasmataceae.

PMID- 9157136
TI  - PCR detection of Pneumocystis carinii in bronchoalveolar lavage specimens:
      analysis of sensitivity and specificity.
AB  - Although PCR detection of Pneumocystis carinii DNA has been described, little is
      known about the sensitivity or specificity of the assay in routine laboratory
      practice. We had the unique opportunity to use a bronchoalveolar lavage (BAL)
      specimen bank with samples for which the direct examination results for P.
      carinii were known. DNA purified from 129 selected specimens was amplified by
      using the primers described previously (A. E. Wakefield, F. J. Pixley, S.
      Banerji, K. Sinclair, R. F. Miller, E. R. Moton, and J. M. Hopkin, Mol. Biochem.
      Parasitol. 43:69-76, 1990). Of the 129 specimens, 37 were positive for P. carinii
      by direct examination. All 37 specimens were positive for P. carinii by PCR,
      yielding a 100% sensitivity and 100% negative predictive value for the assay. An
      additional 23 specimens were repeatedly positive for P. carinii by PCR but were
      not positive by direct examination. Review of the patient charts for these
      specimens with discordant results demonstrated that five of the patients were
      actually positive for P. carinii, as determined by either biopsy or examination
      of repeat or prior BAL specimens. A response to empiric therapy for P. carinii
      pneumonia was seen in an additional two patients. Of the remaining specimens, 8
      produced no significant isolates other than P. carinii, while 12 contained
      culture-confirmed significant respiratory pathogens in addition to P. carinii
      (two fungal, nine bacterial, and one viral pathogen). Cytomegalovirus, which was
      of unknown significance, was isolated from 16 additional specimens. Overall, the
      specificity of the PCR assay was 79.3% compared to the results of direct
      examination. We hypothesized that the apparently poor specificity of the PCR
      assay was due to the increased sensitivity of the assay compared to that of
      direct examination. The sensitivity of the PCR assay was therefore assessed with
      BAL specimens containing P. carinii cysts. Serial dilutions of this preparation
      were evaluated by direct examination and PCR. PCR was found to be 100-fold more
      sensitive than direct examination, which detected one to two cysts per
      amplification. No false-positive results were detected in controls containing no
      DNA or by using target DNA from various fungal, viral, or bacterial respiratory
      pathogens. We conclude that PCR detection of P. carinii in BAL specimens is very
      sensitive and should be considered for patients whose specimens do not yield a
      diagnosis. The increased sensitivity of the PCR assay may help to identify those
      patients with low-titer infections who might benefit from directed antibiotic
      therapy for P. carinii and would otherwise be missed by direct examination alone.

PMID- 9157137
TI  - Vulval swabs as alternative specimens for ligase chain reaction detection of
      genital chlamydial infection in women.
AB  - A ligase chain reaction (LCR)-based assay was recently shown to be highly
      sensitive and specific for the detection of Chlamydia trachomatis not only in
      cervical specimens but also in first-void urine (FVU) specimens form women. The
      suitability of using vulval swabs as an alternative specimen that can be obtained
      by noninvasive means for the diagnosis of genital chlamydial infection by LCR was
      investigated. In a first study of 169 women, vulval, endocervical, and urethral
      swabs were tested by LCR, culture, and a combination of enzyme immunoassay (EIA)
      followed by confirmation by direct fluorescent-antibody assay (DFA), and the
      results were compared with those obtained by testing FVU specimens by LCR and EIA
      DFA by using a specimen from an infected patient as a reference standard. Of the
      169 women tested, 27 (16%) were shown to be infected. Whereas LCR showed high
      sensitivities with all specimen types (85.2% for vulval, urine, and endocervical
      specimens; 92.6% for urethral swabs), the sensitivities of culture and EIA-DFA
      were high only with endocervical swabs (74.1 and 70.4%, respectively), being 22.2
      and 40.7%, respectively, with vulval swabs. In addition, urine testing by EIA-DFA
      also showed a poor sensitivity (48.1%). In order to further compare LCR
      performance with vulval specimens to that with FVU specimens, a second study was
      carried out with specimens from 312 women, of whom 26 were infected. Comparable
      sensitivity was obtained by LCR with vulval swabs (88.5%; 23 of 26) and FVU
      specimens (92.3%; 24 of 26). The results indicate that vulval swabs may serve as
      suitable alternative to specimens that can be obtained by noninvasive means for
      the detection of C. trachomatis by LCR.

PMID- 9157138
TI  - Determination of anti-streptolysin O antibody titer by a new passive
      agglutination method using sensitized toraysphere particles.
AB  - We developed a new method for determining the anti-streptolysin O (ASO) titer on
      the basis of a passive agglutination reaction. This new method uses Toraysphere
      particles sensitized with streptolysin O. This method was used to measure the ASO
      titer in 130 serum samples (from 31 patients with post-streptococcal
      glomerulonephritis, 26 patients with group A streptococcal pharyngitis, 5
      patients with scarlet fever, 29 patients with non-group A streptococcal
      pharyngitis, 20 healthy children, and 19 healthy adults). The results were
      compared with those obtained simultaneously by two conventional methods, the
      Rantz-Randall and the NA-Latex-ASL methods. The results obtained by the
      Toraysphere method showed an excellent correlation with those obtained by each
      conventional method (correlation coefficients, 0.932 for the Rantz-Randall method
      and 0.913 for the NA-Latex-ASL method). The performance of each method was
      evaluated with respect to the clinical and microbiological diagnoses for each
      patient. The sensitivity, specificity, positive predictive value, and negative
      predictive value for the Toraysphere method were 76, 84, 81, and 79%,
      respectively. The corresponding values for the Rantz-Randall method were 48, 78,
      67, and 62%, respectively, while those for the NA-Latex-ASL method were 60, 82,
      76, and 69%, respectively. Because the Toraysphere method is simple and
      reproducible, has a short reaction time, and has a clear-cut endpoint for the
      analysis, we recommend it for routine use in determining the ASO titer in the
      clinical microbiology laboratory.

PMID- 9157139
TI  - Molecular fingerprinting of Mycobacterium tuberculosis on a Caribbean island with
      IS6110 and DRr probes.
AB  - Because of a substantial increase in human immunodeficiency virus (HIV) infection
      and HIV-linked tuberculosis in the Caribbean, a molecular fingerprinting study of
      clinical isolates of Mycobacterium tuberculosis isolated at the Pasteur Institute
      of Guadeloupe from 1994 to 1995 was undertaken with the insertion sequence IS6110
      and the direct repeat DRr probes. We present the results for 72 isolates from 51
      patients. A major cluster (cluster A) representing isolates from 12 patients
      (24%) was detected upon PvuII-IS6110 fingerprinting, which revealed a pattern of
      four bands among these isolates. Homogeneity was retained when the isolates were
      further analyzed with the DRr probe or further characterized by AluI and SmaI-DRr
      restriction fragment length polymorphism analysis. The isolates of cluster A,
      from 10 men and 2 women, was present in people of all ages and of different
      ethnic and geographical backgrounds, and infection with these isolates was
      independent of the HIV status of the patients (except for 2 HIV-positive patients
      from the same ward from whom the tubercle bacilli were isolated at the same
      time). The percentage of reactivation versus active transmission events could not
      be precisely determined in this study. These results are discussed on the basis
      of the genetic advantage of predominant clusters and/or specific characteristics
      of the settings from which a similar cluster of isolates with four bands has so
      far been reported, which include South Africa, French Polynesia, and Guadeloupe.

PMID- 9157140
TI  - Comparison of agar dilution, broth microdilution, disk diffusion, E-test, and
      BACTEC radiometric methods for antimicrobial susceptibility testing of clinical
      isolates of the Nocardia asteroides complex.
AB  - An evaluation was undertaken to determine the optimal method for the in vitro
      susceptibility testing of 26 Nocardia asteroides complex isolates to the
      following antimicrobial agents: amikacin, ampicillin, amoxicillin-clavulanate,
      ceftriaxone, ciprofloxacin, erythromycin, imipenem, minocycline, and trimethoprim
      sulfamethoxazole. Five testing methods were studied including the agar dilution,
      broth microdilution, and disk diffusion methods, the epsilometer test (E-test),
      and the BACTEC radiometric method. Results for each antimicrobial agent and each
      testing method were interpreted as indicating susceptibility, intermediate
      susceptibility, or resistance according to current guidelines of the National
      Committee for Clinical Laboratory Standards (NCCLS) for bacteria that grow
      aerobically and were then compared to a "gold standard" susceptibility test
      result. The gold standard result for each Nocardia isolate was established by a
      consensus of the results of the majority of testing methods used in the study.
      When the results were combined for all antimicrobial agents tested against all
      Nocardia isolates by all methods, the BACTEC radiometric method produced the
      highest level of agreement (97.9%) with the consensus results and had the fewest
      very major (n = 1), major (n = 2), and minor (n = 2) errors. In contrast, the
      results of the agar dilution method were in least agreement (93.2%) with the
      consensus results, and this method also produced the most very major (n = 8),
      major (n = 4), and, along with the disk diffusion method, minor (n = 6) errors.
      For all test methods, interpretive errors were most frequent when testing
      ampicillin or amoxicillin-clavulanate. Moreover, for all Nocardia nova isolates
      tested, ampicillin susceptibility results by any of the testing methods were not
      in agreement with the results of testing for beta-lactamase by the nitrocefin
      (Cefinase) disk method. We conclude that among the methods evaluated, the BACTEC
      radiometric method appeared to be the best for determining the in vitro
      susceptibilities of members of the N. asteroides complex to a panel of nine
      antimicrobial agents. However, none of the test methods, including the BACTEC
      method, accurately predicted the ampicillin resistance of the N. nova isolates
      tested, all of which produced beta-lactamase. Presuming that this beta-lactamase
      hydrolyzes ampicillin, this disparity may relate to the NCCLS breakpoints that
      were used, which may require modification for this antimicrobial agent when
      tested against N. nova isolates.

PMID- 9157141
TI  - Natural infection of small mammal species in Minnesota with the agent of human
      granulocytic ehrlichiosis.
AB  - The natural reservoirs for the agent of human granulocytic ehrlichiosis (HGE) are
      suspected to be the small mammals that host immature stages of Ixodes scapularis
      ticks. To determine if such small mammals are naturally infected, we collected
      blood and serum samples from small mammal species in rural and suburban areas of
      Minneapolis and St. Paul, Minn. Samples were collected from white-footed mice
      (Peromyscus leucopus), eastern chipmunks (Tamias striatus), southern red-backed
      voles (Clethrionomys gapperi), and insectivorous shrews (Blarina brevicauda and
      Sorex cinereus). Blood samples were tested by PCR for active infection with the
      HGE agent, and sera from P. leucopus mice were tested for serologic evidence of
      infection by indirect immunofluorescence. PCR analyses revealed the presence of
      HGE agent DNA in 20 of the 190 samples (10.5%) tested. Of the 119 P. leucopus
      mouse serum samples that were analyzed, 12 (10.1%) contained Ehrlichia equi
      antibodies. In 3 of 119 (2.5%) P. leucopus mice from which both blood and serum
      were collected. HGE agent DNA and antibodies against E. equi were present.
      Animals with evidence of infection with the HGE agent are widely distributed
      around the Minneapolis-St. Paul area in regions with known I. scapularis tick
      activity. Small mammals that are frequent hosts for larval I. scapularis ticks
      and that are found in areas where HGE occurs are likely to be a major reservoir
      from which infected ticks that bite humans are derived.

PMID- 9157142
TI  - Comparison of four molecular typing methods for evaluating genetic diversity
      among Candida albicans isolates from human immunodeficiency virus-positive
      patients with oral candidiasis.
AB  - Candida albicans strain delineation by karyotyping. NotI restriction pattern
      analysis, hybridization with specific probe 27A, and PCR fingerprinting with the
      phage M13 core sequence were performed with 30 isolates from the oral cavities of
      30 human immunodeficiency virus (HIV)-infected patients and 8 reference strains.
      Within the panel of clinical isolates, 20 were geographically related, although
      10 isolates were susceptible to fluconazole and 10 isolates were resistant to
      fluconazole. The remaining isolates used in this study were fluconazole resistant
      and geographically unrelated. A composite DNA type was defined for each of the
      strains as the combination of types obtained by the four molecular methods. By
      this procedure, a great diversity of DNA types was found among isolates from the
      oropharynges of HIV-infected individuals with oral candidiasis. This diversity
      was not reduced when isolates were evaluated on the basis of whether they came
      from the same geographical locale and whether they were fluconazole resistant.
      These data refute the idea of a clonal origin for fluconazole-resistant strains
      among HIV-positive patients. Karyotyping was the least discriminatory method,
      yielding 19 DNA types among the 38 strains analyzed. Conversely, hybridization
      with the 27A probe showed a unique DNA pattern for each of the strains examined
      in this study. Our results demonstrate that at least two different molecular
      methods are needed for Candida albicans typing and that there is a great deal of
      strain variation within the species, irrespective of place of origin or
      antifungal resistance patterns.

PMID- 9157143
TI  - Improved detection of bacterial growth in continuous ambulatory peritoneal
      dialysis effluent by use of BacT/Alert FAN bottles.
AB  - Culture-negative peritonitis is a major complication for patients on continuous
      ambulatory peritoneal dialysis (CAPD) and precludes organism-specific therapy.
      The aim of the present study was to compare inoculation of 10 ml of CAPD effluent
      into BacT/Alert blood culture bottles (FAN [fastidious antimicrobic
      neutralizing], BacTAlert aerobic [BTA], and BacT/Alert anaerobic [BTAn] bottles)
      to our conventional method of using 50 ml of concentrated CAPD effluent to
      inoculate peptone broth bottles (BD bottles) and MacConkey agar and blood agar
      medium (BA-MAC). The FAN, BTA, and BTAn bottles were monitored automatically in
      the BacT/Alert blood culture instrument. A total of 207 CAPD effluents were
      studied, and in 97 bacteria were detected by at least one method. Compared to BTA
      bottles (79 of 97; 81.4%), BTAn bottles (78 of 97; 80.4%), and BD bottles (88 of
      97; 90.7%), the single best broth medium for detecting bacterial growth in CAPD
      effluents was the FAN bottle (90 of 97 effluents; 92.8%). A total of 125
      bacterial species were detected by any method, and the majority (91.8%) of CAPD
      effluents were infected with a single species. A combination of FAN and BTAn
      bottles detected 111 of 125 (88.8%) of all organisms, whereas a combination of BD
      bottles and BA-MAC detected 107 of 125 (85.6%) of all organisms. One or more
      organisms that would have been completely missed by the conventional method with
      BD bottles and BA-MAC were detected in 18 CAPD effluents. Of these 18 CAPD
      effluents, 6 showed no growth by the conventional method with BD bottles and BA
      MAC. On the basis of our data, the most sensitive and least labor intensive
      method was direct inoculation of 10 ml of CAPD effluent into a FAN bottle and a
      BTAn bottle, which could be automatically monitored by the BacT/Alert blood
      culture instrument. On the basis of case definitions for peritonitis, the
      sensitivities and specificities of the methods with FAN and BTAn bottles and with
      BD bottles and BA-MAC were 81.1 and 98.8% and 74.5 and 96.5%, respectively.

PMID- 9157144
TI  - Detection and characterization of the coli surface antigen 6 of enterotoxigenic
      Escherichia coli strains by using monoclonal antibodies.
AB  - We describe, for the first time, the production of monoclonal antibodies (MAbs)
      against coli surface antigen 6 (CS6) of enterotoxigenic Escherichia coli (ETEC)
      and their use for characterization and diagnosis of CS6. Two MAbs, MAbs CS6
      20:11:9 and CS6-2A:14, were produced by immunizing mice with purified CS6 or CS6
      containing bacterial extracts. The MAb specificity was demonstrated by enzyme
      linked immunosorbent assay (ELISA), immunoblotting, and immunoelectron
      microscopy, which showed that the MAbs bound to CS6-expressing bacteria as well
      as to purified CS6 and CS6 structural subunits but not to CS6-negative bacteria
      or other purified ETEC colonization factors. By using bacterial recombinants,
      i.e., strains with a complete CS6 operon or parts thereof, it was found that both
      MAbs were specific for CssB, one of the two structural subunits of CS6. Although
      the MAbs bound specifically to the entire surface of CS6-expressing bacteria, no
      structure of CS6 could be identified. The usefulness of the MAbs for the
      detection of CS6 was evaluated in an inhibition ELISA and in a dot blot test.
      Ninety-two ETEC strains with known colonization factors were analyzed, and all
      CS6-positive strains were identified by either assay with MAb CS6-2A:14, whereas
      MAb CS6-20:11:9 failed to identify two CS6-positive strains; in no instance was
      any CS6-negative strain identified by either of the MAbs. Parallel analyses of 48
      strains with a gene probe specific for the other structural subunit of CS6, i.e.,
      CssA, and the MAb-based assays gave identical results, suggesting the
      simultaneous presence of both subunits.

PMID- 9157145
TI  - Detection of human immunodeficiency virus type 1 (HIV-1) DNA and RNA sequences in
      HIV-1 antibody-positive blood donors in Uganda by the Roche AMPLICOR assay.
AB  - The ability of commercially available PCR-based assays to accurately detect or
      quantitate human immunodeficiency virus type 1 (HIV-1) DNA or RNA in individuals
      predominantly infected with HIV-1 subtypes A and D is not known. Therefore,
      peripheral leukocytes from 43 individuals in Kampala, Uganda, positive for HIV by
      the Western blot (immunoblot) assay were tested by using the Roche AMPLICOR HIV-1
      assay for the detection of DNA gag sequences. Plasma from these same individuals
      was tested by using the Roche HIV-1 AMPLICOR MONITOR HIV-1 assay for the
      quantitation of HIV-1 RNA gag sequences. In addition, peripheral leukocytes were
      tested for HIV-1 DNA by using a lower annealing temperature or a different primer
      pair for the HIV-1 pol region. The proportions of individuals with detectable HIV
      1 DNA and RNA gag sequences by the Roche assays were 74 and 90%, respectively.
      The proportions positive for HIV-1 DNA sequences by using a 50 degrees C
      annealing temperature or the pol primer pair were 71 and 98%, respectively. In
      summary, the standard Roche assay did not detect HIV-1 DNA sequences in a
      significant number of HIV-1-infected individuals in Uganda. However, use of a pol
      primer pair increased the sensitivity of the assay to 98%. The sensitivity of the
      Roche AMPLICOR MONITOR assay for the detection and quantitation of HIV-1 RNA
      sequences was significantly higher than that of the DNA-based assay, but the
      efficiency of the assay, and hence, the accuracy of the values obtained with RNA,
      is not known. Modifications to existing assays are needed to enhance the
      sensitivities and accuracies of these commercially available assays for use in
      developing countries where non-B HIV-1 subtypes predominate.

PMID- 9157146
TI  - Evaluation of latex reagents for rapid identification of Candida albicans and C.
      krusei colonies.
AB  - A total of 322 yeast strains and yeastlike organisms belonging to the genera
      Candida, Cryptococcus, Geotrichum, Saccharomyces, and Trichosporon were tested
      with the new monoclonal antibody-based Bichro-latex albicans and Krusei color
      latex tests. Comparison of results with those obtained by conventional
      identification methods showed 100% sensitivity for both latex tests and 100% and
      95% specificity for the Bichro-latex albicans and Krusei color tests,
      respectively. Because the test is easy to read and quick to perform, the Bichro
      latex albicans test may be useful for rapid identification of Candida albicans
      colonies in the clinical laboratory.

PMID- 9157147
TI  - Comparison and application of ribosome spacer DNA amplicon polymorphisms and
      pulsed-field gel electrophoresis for differentiation of methicillin-resistant
      Staphylococcus aureus strains.
AB  - Analysis of sequences in the fragments of the 16S-23S rRNA intergenic spacer
      region by the ribosome spacer PCR (RS-PCR) can differentiate strains of
      methicillin-resistant Staphylococcus aureus (MRSA). We compared this technique
      with pulsed-field gel electrophoresis (PFGE) for typing MRSA strains and its
      application during an investigation of an outbreak. A total of 180 isolates of
      MRSA collected from various hospital laboratories within the United Kingdom and
      elsewhere were typed by PFGE and RS-PCR. PFGE identified 17 different types among
      the 180 strains examined, and RS-PCR generated 13 different types. PFGE could
      detect minor genetic variations among the isolates and could identify the
      variants which were not discriminated by RS-PCR. Four unique strain types
      detected by PFGE were not detected by RS-PCR. When applied to typing the outbreak
      related strains from the vascular surgery unit at the General Infirmary at Leeds,
      the results of RS-PCR were identical to those of PFGE. Our results have shown
      that RS-PCR is a rapid, inexpensive technique that is highly reproducible and
      almost as discriminatory as PFGE for typing MRSA isolates and should be useful in
      the local investigation of MRSA outbreaks.

PMID- 9157148
TI  - A sensitive, type-specific, fluorogenic probe assay for detection of human
      papillomavirus DNA.
AB  - A simple method for the detection of a number of human papillomavirus (HPV)
      genotypes associated with cervical cancer has been developed. The assay exploits
      the 5'-->3' exonucleolytic activity of Taq DNA polymerase to increase the signal
      from fluorescent dyes by releasing them from genotype-specific probes during PCR.
      The probes are oligonucleotides with a 5' reporter dye (6-carboxyfluorescein), a
      quencher dye (6-carboxy-tetramethyl-rhodamine), and a phosphate-blocked 3' end.
      In the intact probe, the proximity of the reporter and the quencher results in
      suppression of reporter fluorescence by Forster-type energy transfer (V. T.
      Forster. Ann. Phys. 2:55-75, 1948). If the probe is bound downstream of either
      primer during PCR, the 5'-->3' exonucleolytic activity of Taq polymerase degrades
      it, allowing the reporter to diffuse away from the quencher, which results in an
      increase in reporter fluorescence. The increased fluorescence is directly related
      to the amount of target DNA and can be detected with an automated fluorometer.
      Probes for the L1 region of the cervical-cancer-associated HPV types 16, 18, 31,
      33, and 35 were synthesized and the assays were optimized. The most sensitive
      assay can detect as few as two copies of HPV DNA in human cervical specimens.

PMID- 9157149
TI  - Characterization of Escherichia coli O157:H7 and other Shiga toxin-producing E.
      coli serotypes isolated from sheep.
AB  - The isolation and characterization of Escherichia coli O157:H7 and non-O157 Shiga
      toxin-producing E. coli (STEC) strains from sheep are described. One flock was
      investigated for E. coli O157:H7 over a 16-month period that spanned two summer
      and two autumn seasons. Variation in the occurrence of E. coli O157:H7-positive
      sheep was observed, with animals being culture positive only in the summer months
      but not in the spring, autumn, or winter. E. coli O157:H7 isolates were
      distinguished by pulsed-field gel electrophoresis (PFGE) of chromosomal DNA and
      toxin gene restriction fragment length polymorphism (RFLP) analysis. Ten PFGE
      patterns and five RFLP patterns, identified among the isolates, showed that
      multiple E. coli O157:H7 strains were isolated from one flock, that a single
      animal simultaneously shed multiple E. coli O157:H7 strains, and that the strains
      shed by individuals changed over time. E. coli O157:H7 was isolated only by
      selective enrichment culture off 10 g of ovine feces. In contrast, strains of
      eight STEC serotypes other than O157:H7 were cultured from feces of sheep from a
      separate flock without enrichment. The predominant non-O157 STEC serotype found
      was O91:NM (NM indicates nonmotile), and others included O128:NM, O88:NM, O6:H49,
      and O5:NM. Irrespective of serotype, 98% of the ovine STEC isolates possessed
      various combinations of the virulence-associated genes for Shiga toxin(s) and the
      attaching-and-effacing lesion (stx1, stx2, and eae), suggesting their potential
      for human pathogenicity. The most common toxin-eae genotype was positive for
      stx1, stx2, and eae. A Vero cell cytotoxicity assay demonstrated that 90% of the
      representative STEC isolates tested expressed the toxin gene. The report
      demonstrates that sheep transiently shed a variety of STEC strains, including E.
      coli O157:H7, that have potential as human pathogens.

PMID- 9157150
TI  - Detection of Mycobacterium tuberculosis in BACTEC 12B broth cultures by the Roche
      Amplicor PCR assay.
AB  - To evaluate the ability of the Amplicor MTB Assay to detect Mycobacterium
      tuberculosis complex (MTBC) organisms in BACTEC 12B broth cultures, 249 cultures
      with a growth index (GI) of > or = 20 from 160 patients were tested
      retrospectively. Specimens were processed by standard methods, and then BACTEC
      12B vials and Middlebrook 7H11/7H115 plates were inoculated, incubated, and
      interpreted in accordance with the manufacturer's instructions and laboratory
      protocol. From 12B vials with a GI of > or = 20, and aliquot of broth was removed
      and frozen at -20 degrees C until assayed by PCR. PCR results were compared to
      those obtained by the usual laboratory protocol, whereby MTBC organisms were
      identified by a DNA probe assay performed on broth from 12B vials with a GI or >
      or = 300 or on colonies from solid medium. Of the 249 broth cultures evaluated,
      142 contained mycobacteria, including 44 that contained MTBC organisms. Of these
      44 cultures, 41 were PCR positive; the 3 that were PCR negative were blood
      specimens collected in an Isolator tube. All 98 cultures with nontuberculous
      mycobacteria and the 107 that did not contain mycobacteria were PCR negative.
      Thus, the sensitivity and specificity of PCR were 93 and 100%, respectively. For
      those culture sin which MTBC organisms were identified by both the DNA probe and
      PCR assays, the mean time from specimen inoculation to detection and
      identification of MTBC organisms was 16 (range, 4 to 26) days for the PCR and 28
      (range, 13 to 43) days for the DNA probe assay (P < 0.0001). In summary, PCR is a
      rapid, reliable method for detection of MTBC organisms in BACTEC 12B broth
      cultures with a GI of > or = 20.

PMID- 9157151
TI  - Assessment of detection of Candida mannoproteinemia as a method to differentiate
      central venous catheter-related candidemia from invasive disease.
AB  - The proper management of candidemic patients is controversial because of the
      difficulties of an early differentiation of central venous catheter (CVC)-related
      candidemia from deep-seated invasive Candida infection. In particular, more
      information on possible markers of invasive disease is needed. We performed a
      retrospective, pilot investigation to assess the diagnostic potential of a dot
      immunobinding assay for Candida mannoprotein antigen in serial serum samples from
      31 candidemic patients in the setting of hematologic malignancy. Mannoproteinemia
      (antigenemia) was detected in 1 of 14 (7.1%) patients with transient or CVC
      related candidemia and in 13 of 17 (76.5%) patients with non-CVC-related
      persistent candidemia. Of the 11 subjects of this latter group with documented
      tissue invasion, 10 (91%) were antigenemic. The patients belonging to the
      different categories did not significantly differ in the duration of candidemia,
      nor was there any significant difference among the different groups of subjects
      either in the number of serum samples examined or in their collection time during
      candidemia. The day of the first antigenemic sample during candidemia greatly
      varied among subjects with invasive infection, although on average
      mannoproteinemia was detectable by the first week of candidemia. In summary, our
      data demonstrate a correlation between mannoproteinemia and tissue invasion by
      Candida spp. in candidemic patients and suggest that mannoprotein detection by
      our method has a potential for the diagnosis of invasive candidiasis in these
      subjects.

PMID- 9157153
TI  - Comparison of axenic and monoxenic media for isolation of Acanthamoeba.
AB  - Acanthamoeba is a genus of ubiquitous, free-living amebae that can be difficult
      to isolate by standard microbiologic techniques. We retrospectively reviewed the
      laboratory records of patients with ocular acanthamoebic infection for the period
      from January 1973 to June 1996 and found that Acanthamoeba isolates were
      recovered from 73, 71, and 70% of clinical specimens inoculated onto buffered
      charcoal-yeast extract agar (BCYE), nonnutrient agar with live or dead
      Escherichia coli, and tryptic soy agar (TSA) with horse or sheep blood,
      respectively. We then prospectively compared the recovery of a corneal isolate of
      Acanthamoeba on commercial media from Remel and BBL (TSA with 5% sheep blood, TSA
      with 5% horse blood, TSA with 5% rabbit blood, V agar, chocolate agar, BCYE, and
      selective BCYE with polymyxin B, anisomycin, and vancomycin) and on axenic and
      monoxenic media prepared with live or dead bacteria (Enterobacter aerogenes, E.
      coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Serratia marcescens,
      Staphylococcus aureus, and Stenotrophomonas maltophilia). Good recovery of
      trophozoites was obtained on BCYE, TSA with rabbit blood, TSA with horse blood,
      and Remel TSA with sheep blood. BBL TSA with horse blood or rabbit blood provided
      good recovery of cysts. All species of live or dead bacteria yielded good
      recovery of trophozoites; however, only nonnutrient agar with live P. aeruginosa,
      live E. aerogenes, or live S. maltophilia gave good recovery of cysts. TSA with
      either rabbit blood or horse blood, BCYE, and nonnutrient agar prepared with live
      P. aeruginosa, E. aerogenes, or S. maltophilia offer optimal recovery of
      Acanthamoeba.

PMID- 9157152
TI  - Simultaneous detection and strain differentiation of Mycobacterium tuberculosis
      for diagnosis and epidemiology.
AB  - Widespread use of DNA restriction fragment length polymorphism (RFLP) to
      differentiate strains of Mycobacterium tuberculosis to monitor the transmission
      of tuberculosis has been hampered by the need to culture this slow-growing
      organism and by the level of technical sophistication needed for RFLP typing. We
      have developed a simple method which allows simultaneous detection and typing of
      M. tuberculosis in clinical specimens and reduces the time between suspicion of
      the disease and typing from 1 or several months to 1 or 3 days. The method is
      based on polymorphism of the chromosomal DR locus, which contains a variable
      number of short direct repeats interspersed with nonrepetitive spacers. The
      method is referred to as spacer oligotyping or "spoligotyping" because it is
      based on strain-dependent hybridization patterns of in vitro-amplified DNA with
      multiple spacer oligonucleotides. Most of the clinical isolates tested showed
      unique hybridization patterns, whereas outbreak strains shared the same
      spoligotype. The types obtained from direct examination of clinical samples were
      identical to those obtained by using DNA from cultured M. tuberculosis. This
      novel preliminary study shows that the novel method may be a useful tool for
      rapid disclosure of linked outbreak cases in a community, in hospitals, or in
      other institutions and for monitoring of transmission of multidrug-resistant M.
      tuberculosis. Unexpectedly, spoligotyping was found to differentiate M. bovis
      from M. tuberculosis, a distinction which is often difficult to make by
      traditional methods.

PMID- 9157154
TI  - Propagation of granulocytic Ehrlichia spp. from human and equine sources in HL-60
      cells induced to differentiate into functional granulocytes.
AB  - Ehrlichia spp. from human and equine sources in the northeastern Unites States
      were detected by PCR, isolated, and propagated in the HL-60 promyelocytic
      leukemia cell line. Growth of Ehrlichia from both equine and human sources was
      enhanced by addition of retinoic acid, which causes granulocytic differentiation
      of the HL-60 cells. DNA sequencing of a portion of the 16S rDNA gene supported
      the hypothesis that the same pathogen was responsible for both equine and human
      granulocytic ehrlichiosis.

PMID- 9157156
TI  - Identification of noncytopathic equine rhinovirus 1 as a cause of acute febrile
      respiratory disease in horses.
AB  - Equine rhinovirus 1 (ERhV1) is a recognized cause of acute febrile respiratory
      disease in horse, although the virus is rarely isolated from such animals,
      despite seroprevalence rates as high as 50% in some horse populations. Recently,
      ERhV1 has been shown to be most closely related to foot-and-mouth disease virus,
      raising questions as to its disease associations in horses. We report that ERhV1
      infection was the likely cause of two separate outbreaks of severe febrile
      respiratory disease which involved more than 20 horses. Attempts to isolate ErhV1
      from nasopharyngeal swabs by conventional cell culture methods were unsuccessful,
      in that cytopathology was not observed. Viral antigen was detected by
      immunofluorescence assay in the cytoplasm of cells infected with 10 of 15
      nasopharyngeal swab samples, indicating the presence and presumably replication
      of ERhV1. A rise in serum neutralizing antibody titer between acute- and
      convalescent-phase sera confirmed that ERhV1 was causatively associated with one
      of the outbreaks. ERhV1 RNA was detected in nasopharyngeal swabs collected from
      all horses during the acute phase of disease by reverse transcription-PCR.
      Nucleotide sequencing of amplified products showed that within each outbreak a
      single strain of ERhV1 was involved but that distinct viruses were involved in
      each outbreak. A retrospective study of samples from nine other outbreaks of
      respiratory disease in horses suggested ERhV1 etiology in at least two of these.
      We conclude that the relative importance of ERhV1 as a cause of acute febrile
      respiratory disease in horses has been underestimated due to failure in many
      instances to isolate virus by conventional cell culture methods.

PMID- 9157155
TI  - Diagnosis of vascular catheter-related bloodstream infection: a meta-analysis.
AB  - Catheter-related bloodstream infections increased in incidence during the past
      decade, causing significant morbidity, mortality, and excess hospital costs.
      Absence of inflammation at the catheter site in most cases makes clinical
      diagnosis uncertain. The relative accuracy and cost-effectiveness of different
      microbiologic tests for confirming that bloodstream infection is catheter related
      have remained unclear. A meta-analysis of published studies was conducted
      regarding the accuracy of diagnostic test methods using pooled sensitivity and
      specificity and summary receiver operating characteristic (ROC) curve analysis.
      The cost for each test was estimated by methods published by the College of
      American Pathologists. Costs of catheter replacement and antibiotic therapy for
      false positive results were included in the cost per accurate test result. Twenty
      two studies evaluating six test methods met inclusion criteria for the meta
      analysis. Accuracy increased in ROC analysis for catheter segment cultures with
      increasing quantitation (P = 0.03) (i.e., quantitative > semiquantitative >
      qualitative) largely due to an increase in specificity. The highest Youden index
      (mean = 0.85) was observed with quantitative catheter segment culture, the only
      method with pooled sensitivity and specificity above 90%. For blood culture
      methods, there was no statistically significant trend toward increased accuracy.
      The unpaired quantitative catheter blood culture offered the lowest cost per
      accurate test result but was only 78% sensitive. In conclusion, quantitative
      culture was the most accurate method for catheter segment culture, and unpaired
      quantitative catheter blood culture was the single most cost-effective test,
      especially for long-term catheters.

PMID- 9157157
TI  - Serologic and molecular detection of granulocytic ehrlichiosis in Rhode Island.
AB  - A new indirect fluorescent-antibody (IFA) assay with antigen produced in vitro in
      the human promyelocytic leukemia cell line HL60 was used to identify the first
      recognized case of human granulocytic ehrlichiosis in Rhode Island. This IFA
      assay was used to detect granulocytic ehrlichiae in white-footed mice and in a
      dog inhabiting the area surrounding the patient's residence. Host-seeking Ixodes
      scapularis ticks found in the same habitat also were infected. I. scapularis
      ticks collected from other locations were fed on dogs and New Zealand White
      rabbits to assess the competency of these species as hosts of granulocytotropic
      Ehrlichia. Tick-induced infections of dogs were confirmed by serologic testing,
      tissue culture isolation, and PCR amplification, whereas several rabbits
      seroconverted but were PCR and culture negative. PCR amplification of the 16S
      rRNA gene and DNA sequencing of the PCR products or culture isolation was used to
      confirm granulocytic Ehrlichia infections in humans, dogs, white-footed mice, and
      ticks.

PMID- 9157158
TI  - Rapid screening of point mutations of the Neisseria gonorrhoeae parC gene
      associated with resistance to quinolones.
AB  - To detect quinolone resistance-associated mutations within the Asp-86, Ser-87,
      Ser-88, and Glu-91 codons of the Neisseria gonorrhoeae parC gene, we developed a
      rapid and simple assay based on amplification of the regions of the parC gene
      containing the mutations sites by PCR and digestion of the PCR products with
      restriction enzymes. By using the method of primer-specified restriction site
      modification, artificial SalI, PstI, EcoRI, and HinfI restriction sites were
      created in the regions containing the Asp-86, Ser-87, Ser-88, and Glu-91 codons,
      respectively. The mutations generating alterations at Asp-86, Ser-87, Ser-88, and
      Glu-91 were detected as failures of SalI, PstI, EcoRI, and HinfI to digest the
      respective PCR products. Fifty-five clinical strains of N. gonorrhoeae were
      examined for mutations in the parC gene by this assay. Appropriate mutations at
      either the Asp-86, Ser-87, Ser-88, or Glu-91 codon were detected in each of 11
      strains in which a mutation had previously been observed by DNA sequencing. This
      rapid and simple assay could be a useful device for screening genetic alterations
      in the parC gene associated with resistance to quinolones in N. gonorrhoeae.

PMID- 9157159
TI  - Rapid screening method for identification of cholera toxin-producing Vibrio
      cholerae O1 and O139.
AB  - A novel method of identifying cholera enterotoxin (CT)-producing Vibrio cholerae
      serogroups O1 and O139 was developed. The method uses degradation of NAD as a
      specific biochemical marker for the CT-producing strains. The substrate NAD at a
      concentration of 100 mumol/liter was markedly degraded when it was incubated at
      37 degrees C for 2 h with the CT-producing stains at a final cell density
      equivalent to that of a twofold dilution of a McFarland no. 1 standard. NAD
      degradation was monitored by an enzyme-amplified color development assay.
      Subsequent tests conducted with a total of 119 strains of V. cholerae, including
      both clinical and environmental isolates, confirmed a significant correlation
      between NAD degradation and CT production for all V. cholerae strains belonging
      to serogroups O1 and O139. Since 2 of 11 non-O1, non-O139 V. cholerae strains not
      carrying the CT gene degraded NAD, serotyping of the strains prior to the test is
      recommended.

PMID- 9157160
TI  - Rapid diagnosis of Legionella pneumophila serogroup 1 infection with the Binax
      enzyme immunoassay urinary antigen test.
AB  - The Binax legionella urinary antigen (LUA) enzyme immunoassay (Binax, Portland,
      Maine) was evaluated in 159 patients with suspected or proven legionellosis and
      209 controls. A positive LUA test was found in 37% of patients with suspected
      legionellosis overall and in 83% of those with proven Legionella pneumophila
      serogroup 1 infection. The sensitivity of the LUA test was significantly greater
      than that of the direct fluorescent-antigen test (83 versus 42%; P < 0.0001) but
      not significantly different from that of culture (85%) or serology (91%);
      specificity was at least 99.5%.

PMID- 9157161
TI  - Reproducibility problems with the AMPLICOR PCR Chlamydia trachomatis test.
AB  - In an attempt to use an expanded "gold standard" in an evaluation of an antigen
      detection test for Chlamydia trachomatis, the AMPLICOR (Roche Diagnostics
      Systems, Inc., Branchburg, N.J.) PCR Chlamydia trachomatis test and culture were
      used with 591 sets of cervical specimens. Of the 591 specimens assayed, 35 were
      retested due to either an equivocal result by the PCR (19 samples) or a
      discrepancy between the results of culture, PCR, and the antigen detection
      method. During the repeat testing of the samples with equivocal and discrepant
      results, all but one interpretation change was due to the PCR result. In
      addition, upon repeat testing the PCR assay value measured in optical density
      units varied widely for 13 of these specimens. These 13 specimens were then
      tested in triplicate by the manufacturer with primers to the chlamydia plasmid
      and in duplicate with primers to the major outer membrane protein. Only 3 of the
      13 specimens gave the same interpretation with these five replicates. In summary,
      reproducibility problems with the AMPLICOR test should be considered before it is
      incorporated as part of routine testing or used as an expanded gold standard for
      chlamydia testing.

PMID- 9157162
TI  - Widespread geographic distribution of oral Candida dubliniensis strains in human
      immunodeficiency virus-infected individuals.
AB  - Candida dubliniensis is a recently identified chlamydospore-positive yeast
      species associated with oral candidiasis in human immunodeficiency virus (HIV)
      infected (HIV+) patients and is closely related to Candida albicans. Several
      recent reports have described atypical oral Candida isolates with phenotypic and
      genetic properties similar to those of C. dubliniensis. In this study 10 atypical
      chlamydospore-positive oral isolates from HIV+ patients in Switzerland, the
      United Kingdom, and Argentina and 1 isolate from an HIV-negative Irish subject
      were compared to reference strains of C. albicans and Candida stellatoidea and
      reference strains of C. dubliniensis recovered from Irish and Australian HIV+
      individuals. All 11 isolates were phenotypically and genetically similar to and
      phylogenetically identical to C. dubliniensis. These findings demonstrate that
      the geographical distribution of C. dubliniensis is widespread, and it is likely
      that it is a significant constituent of the normal oral flora with the potential
      to cause oral candidiasis, particularly in immunocompromised patients.

PMID- 9157163
TI  - Genetic identification of Mycobacterium bovis BCG by restriction fragment length
      polymorphism analysis of the direct-repeat region.
AB  - Restriction fragment length polymorphism (RFLP) analysis was performed on the
      direct repeat (DR) regions of 14 strains of Mycobacterium bovis BCG. With AluI
      digested DNA, BCG Japanese, Russian, and Mexican had differing RFLP patterns but
      11 strains, including Pasteur, Glaxo, and Tice, had an identical pattern not
      detected in over 60 strains of the M. tuberculosis complex. DR analysis can aid
      in confirming the identification of clinical BCG isolates.

PMID- 9157164
TI  - The effect of Tn916 insertions on contour-clamped homogeneous electrophoresis
      patterns of Enterococcus faecalis.
AB  - Contour-clamped homogeneous gel electrophoresis has increasingly been used and
      has generally been considered the method of choice for the delineation of
      enterococcial strains. It has been suggested that the contour-clamped homogeneous
      electric field (CHEF) electrophoresis digestion patterns of genomic DNA indicate
      the relatedness of strains when SmaI patterns differ by six or fewer bands. To
      evaluate the potential reasons for the diversity of bands among clonally related
      isolates, we studied plasmid-free Enterococcus faecalis FA2-2 and derivatives
      with transposon Tn916 (encoding for tetracycline resistance) insertions on the
      chromosome. We obtained derivatives with seven different Tn916 insertion sites
      and up to two copies of Tn916 on the chromosome, resulting in differences of one
      to seven bands by CHEF electrophoresis; eight different patterns were observed.
      With Tn916 insertions, there was either (i) loss of a band(s) with the generation
      of a new band(s), (ii) the generation of a new band(s) only, or (iii) the loss of
      a band(s) with no new visible band(s). These results indicate that strains can
      have up to seven different SmaI bands by CHEF electrophoresis and still be
      closely related.

PMID- 9157165
TI  - Detection of hepatitis G virus (GB virus C) RNA in human saliva.
AB  - Using PCR and genomic sequencing, we confirmed the presence of and homology
      between hepatitis G virus (HGV) (also called GB virus C) RNA in six serum samples
      and that in two saliva samples obtained from 34 patients with chronic hepatitis C
      virus infections. Thus, HGV may be found outside the circulatory system.

PMID- 9157166
TI  - Rapid diagnosis of enterovirus infection by a new one-step reverse transcription
      PCR assay.
AB  - The AMPLICOR Enterovirus Test was evaluated with 103 cerebrospinal fluid (CSF)
      specimens. Twenty-seven CSF specimens were culture positive. With the AMPLICOR
      test, enterovirus RNA was detected in 34 specimens. Compared with culture, the
      AMPLICOR test gave a sensitivity of 96.3% and a specificity of 100%. The
      sensitivity of culture was 79.4% in comparison with the AMPLICOR test.

PMID- 9157167
TI  - Dissemination of a single clone of methicillin-resistant Staphylococcus aureus
      among Turkish hospitals.
AB  - A collection of 39 methicillin-resistant Staphylococcus aureus (MRSA) stains
      derived from six different hospitals in Ankara and one hospital in Barsa, Turkey,
      were analyzed by multiple genotyping. In agreement with the other genotyping
      assays, pulsed-field gel electrophoresis of DNA macrorestriction fragments
      identified genetic homogeneity among all MRSA isolates studies. It is concluded
      that a major clone of MRSA has spread through a large part of Turkey, causing
      longitudinally persistent colonization in all of the institutions surveyed.

PMID- 9157168
TI  - Ability of commercial ligase chain reaction and PCR assays to diagnose Chlamydia
      trachomatis infections in men by testing first-void urine.
AB  - A total of 287 men (37.6% with symptoms of urethritis) attending a hospital-based
      sexually transmitted disease clinic had urethral swabs tested by culture and by
      direct fluorescent-antibody assay. First-void urine (FVU) was tested for
      Chlamydia trachomatis by commercially available ligase chain reaction (LCR) and
      PCR assays. By using an expanded reference standard, 35 men (12.2%) were found to
      be positive. By performing LCR and PCR, the infection prevalence was found to be
      approximately twice (11.5 and 12.2%, respectively) that determined swab testing.
      The sensitivity values were 94.3% for LCR and 100% for PCR. One of the two
      positive specimens missed by LCR contained inhibitors. PCR produced five false
      positive results and LCR produced one.

PMID- 9157169
TI  - Infected abdominal aortic aneurysm due to penicillin-, ceftriaxone-, and
      cefotaxime-resistant Streptococcus pneumoniae.
AB  - The clinical course for a patient hospitalized with pneumonia and meningitis due
      to penicillin-, ceftriaxone-, and cefotaxime-resistant Streptococcus pneumoniae
      is described. The pneumonia and meningitis responded to antimicrobial therapy,
      but the patient died following rupture of an infected abdominal aortic aneurysm;
      gram-positive cocci resembling S. pneumoniae were detected within the aneurysm.

PMID- 9157170
TI  - False-positive results from cultures of Mycobacterium tuberculosis due to
      laboratory cross-contamination confirmed by restriction fragment length
      polymorphism.
AB  - During 1994, a cross-contamination problem leading to false-positive cultures of
      Mycobacterium tuberculosis was revealed in a mycobacteriology laboratory
      processing 30,000 to 35,000 samples per year. Molecular strain typing based on
      restriction fragment length polymorphism confirmed the contaminations. Out of
      1,439 positive cultures of Mycobacterium tuberculosis, 49 samples from 48
      patients were suspected to be cross-contaminated. In 37 cases, growth was
      observed both in BACTEC vials and on solid media, indicating that the
      contamination took place during the processing of the samples. The majority of
      the contaminated samples had been handled by the same technician.

PMID- 9157171
TI  - Isolation of Mycoplasma hominis from a brain abscess.
AB  - Mycoplasma hominis is a commensal in the genital tract of women and has been
      associated with urogenital and extragenital infections. However, central nervous
      system infections with this organism in adults are very rare. Here we describe
      the recovery of M. hominis from a brain abscess associated with a postpartum
      infection. Seroconversion to the isolated strain was detected by both a metabolic
      inhibition test and an immunoblotting assay. This case demonstrates the
      pathogenic potential of M. hominis and the need for rapid recognition of the
      organism so that appropriate chemotherapeutic intervention can occur.

PMID- 9157172
TI  - Complex polysaccharides as PCR inhibitors in feces: Helicobacter pylori model.
AB  - A model was developed to study inhibitors present in feces which prevent the use
      of PCR for the detection of Helicobacter pylori. A DNA fragment amplified with
      the same primers as H. pylori was used to spike samples before extraction by a
      modified QIAamp tissue method. Inhibitors, separated on an Ultrogel AcA44 column,
      were characterized. Inhibitors in feces are complex polysaccharides possibly
      originating from vegetable material in the diet.

PMID- 9157174
TI  - Contextual strategy instruction: socially/emotionally maladjusted adolescents
      with language impairments.
AB  - Ten socially/emotionally maladjusted adolescents with language impairments
      (SEM/LI) and ten non-impaired adolescents received four treatment sessions in the
      use of a "context clues strategy" for facilitating comprehension of unfamiliar
      words in four sentence types. Both groups improved their ability to use a context
      clues strategy following direct instruction. The SEM/LI subjects exhibited
      greater difficulty with the appositive sentence type than did the non-impaired
      subjects. The results indicated that SEM/LI adolescents probably would benefit
      from receiving direct instruction involving any of the three other sentence types
      (i.e., cause/effect, example, grouping), prior to instruction involving the
      appositive sentence type

PMID- 9157173
TI  - Severe keratitis due to Nocardia farcinica.
AB  - Keratitis due to Nocardia farcinica occurred in a 49-year-old female after
      inappropriate cleaning of her semipermeable rigid contact lenses with basin
      stored water during a holiday in France. N. farcinica was differentiated from
      Nocardia asteroides by its growth at 45 degrees C, acid production from rhamnose,
      its opacification of Middlebrook 7H10 agar, and its marked degree of resistance
      to all cephalosporins, aminoglycosides, tetracyclins, macrolides, and
      trimethoprim-sulfamethoxazole. To the best of our knowledge, this is the first
      reported case of human N. farcinica keratitis, confirming that this microorganism
      can be responsible for serious human disease.

PMID- 9157175
TI  - Neonatal auditory brainstem responses recorded from four electrode montages.
AB  - Simultaneous auditory brainstem responses (ABRs) to click stimuli at 30 and 60 dB
      nHL were recorded from 16 full term neonates with four electrode arrays: vertical
      (Cz-Nape of neck), ipsilateral (Cz-Mi), contralateral (Cz-Mc), and horizontal (Mc
      Mi). Results indicated that ABR waveforms were morphologically similar to those
      recorded in adults: Waves I, III, and V were clearly identifiable and of the same
      polarity in 15 of 16 subjects 60 dB nHL and Wave V was clearly identifiable in 14
      of 16 subjects at 30 dB nHL. Although ABR waves were identified in most cases,
      waveforms expression was variable with different electrode recording montages. It
      is suggested that if a clinician must choose one montage array for recording
      neonatal ABRs at high intensity levels for neurodiagnostic evaluations, the
      ipsilateral recording array is indicated since it displays the highest expression
      of wave components. For screening applications or threshold searching at lower
      stimulus levels, however, either the ipsilateral or vertical montage would be
      justified. Further, caution should be employed when interpreting ABR results in
      neonates recorded with unconventional montages due to the variable expression of
      wave components.

PMID- 9157176
TI  - Intraoral air pressure of alaryngeal speakers during a no-air insufflation
      maneuver.
AB  - Intraoral air pressure was recorded during the production of the consonant
      cognate pairs /p/-/b, /t/-/d, and /s/-/z/ by eight esophageal speakers. These
      consonants were combined with the vowel /a/ to form CV, VCV, and VC syllables and
      produced under two experimental conditions: after the insufflation of air and
      without air insufflation. The purpose was to determine if the voiced-voiceless
      pressure difference associated with the production of cognate pairs would occur
      in the absence of an insufflated air flow source. The results revealed that peak
      intraoral air pressure magnitudes were significantly greater following the
      insufflation of air than without it. Moreover, the voiceless consonants were
      generally produced with greater peak air pressures than the voiced consonants
      under both experimental conditions, although not all contrasts were significantly
      different. Finally, peak air pressure magnitudes were significantly more variable
      in the air insufflation condition. The finding that the esophageal speakers
      exhibited a pressure difference relative to voicing in the absence of an
      insufflated air flow source provides support to the concept that intraoral air
      pressure may be an important variable in regulating and controlling consonant
      production.

PMID- 9157177
TI  - Verbal rehearsal and memory in children with closed head injury: a quantitative
      and qualitative analysis.
AB  - Nine closed head injured (CRI) children (mean age = 11.4 years) with post-onset
      intervals of seven months to eight years were studied. The CRI children ranged
      from mild-moderate to severely impaired. Nine normally developing children (mean
      age = 10.9 years) served as controls. An overt rehearsal free recall task was
      used. Subjects were instructed to "think aloud" following presentation of each
      item to-be-recalled. Quantitative analyses suggested impaired verbal recall and
      inefficient, passive rehearsal strategy use in severely injured subjects. Mild
      moderate subjects performed similarly to controls and exhibited active rehearsal
      strategy use. Qualitative analysis revealed differences between CRI subjects and
      controls' range of rehearsal strategies, monitoring and metamemory. Implications
      for clinical assessment and intervention with respect to use of rehearsal
      strategies are discussed.

PMID- 9157178
TI  - Lexical comprehension and grammatical deficits in children with specific language
      impairment.
AB  - Several accounts of specific language impairment (SLI) in children have appeared
      in the recent literature. One of the most explicit is that of Locke. The purpose
      of the present investigation was to evaluate some of the details of Locke's
      proposal. In the first of two studies, it was found that children with SLI who
      were limited to single-word utterances showed deficits in their lexical
      comprehension. In the second study, a number of children with SLI who had reached
      the grammatical stage of development showed age-appropriate levels of lexical
      comprehension. Although the first of these findings was in keeping with Locke's
      account, the second was not. Additional provisions for this proposal are
      suggested.

PMID- 9157179
TI  - Release of Type II phospholipase A2 immunoreactivity and phospholipase A2
      enzymatic activity from human placenta.
AB  - The aim of this study was to determine whether Type II phospholipase A2 (PLA2) is
      released from late pregnant human placental tissue. Placental explants were
      incubated in vitro and the release of immunoreactive (ir) Type II PLA2 and PLA2
      enzymatic activity into the medium was determined. Both irType II PLA2 and PL2
      enzymatic activity accumulated in the incubation medium in a time-dependent
      manner (P < 0.0001). This release was not associated with a loss of cell membrane
      integrity, as indicated by measurement of the intracellular enzyme, lactate
      dehydrogenase, in the incubation medium. The concentration of irType II PLA2 and
      PLA2 enzyme activity present in incubation medium were significantly correlated
      (P < 0.01). Consistent with the hypothesis that Type II PLA2 may be store in
      secretory granules within human placental tissue, incubation in the presence of a
      membrane depolarising concentration of KCI (60 mM) caused the release of irType
      II PLA2 2.0-fold (P < 0.001). PLA2 enzyme activity released into the incubation
      medium displays biochemical characteristics consistent with those previously
      reported for secretory PLA2 isozymes, that is, a requirement for millimolar
      concentrations of calcium for optimal enzyme activity, inhibited by reducing
      agents, such as dithiothreitol and insensitive to heat inactivation. The data
      obtained in this study establish that irType PLA2 is released from term placenta,
      when incubated in vitro. The release of this extracellularly-active PLA2 isozyme
      may contribute to gestational and labour-associated increases in
      glycerophospholipid metabolism and prostaglandin formation.

PMID- 9157180
TI  - Intrinsic and required dynamics of a simple bat-ball skill.
AB  - Three experiments investigated the coordination dynamics of a simple bat-and-ball
      skill: cyclically striking a ball suspended by a string with a pendular bat. The
      relative phase phi between the bat and ball is dictated by the potential function
      V(phi) = k sin phi and the difference delta omega in their uncoupled frequencies.
      For various delta omega, phi and its standard deviation were measured in the
      absence of any environmental restraints (intrinsic dynamics) and when the ball
      had to reach resistive or nonresistive targets at set distances (required
      dynamics). Results support the dynamical theory of coordination patterns (G.
      Schoner & J.A.S. Kelso, 1988a, 1988c), particularly the hypothesis that required
      dynamics are understandable as the addition of terms to the potential governing
      the intrinsic dynamics.

PMID- 9157181
TI  - Selection by color and form in vision.
AB  - Whether attention to a local part of a visual display can prevent access to
      semantic information in form matching tasks with objects was studied. A first
      picture containing a line segment (the reference) was followed by 2 lateral
      objects also containing a line segment (a target and a distractor). Participants
      matched the line segments according to either their orientation or color. Effects
      of semantic information were assessed by manipulating the semantic relations
      among the pictures surrounding the reference, target, and distractor. Semantic
      information affected performance in the orientation matching task, but not in the
      color matching task. Results suggest the existence of separate selection
      mechanisms in vision. Selection of local colors for response purposes can be
      based on inhibition of the form pathway (eliminating semantic effects on
      matching). Selection within the form pathway can involve a bias toward global
      shape (the picture). Once attention is allocated to global shape associated
      semantic representations are activated and semantic effects on matching emerge.

PMID- 9157182
TI  - Visual search as a function of type of prior experience with target and
      distractor.
AB  - In a visual search task, participants identified the presence of a unique shape
      against a background of homogeneous distractors. Types of prior experience with
      the target, the distractor, or both were examined. In 2 experiments, a
      preexposure (PE) phase was followed by a test phase. The test display consisted
      of a target that was either target or distractor in PE or novel. Distractors were
      either targets or distractors in PE or novel. Reaction time was fastest for novel
      targets with familiar distractors, irrespective of the source of familiarity, and
      slowest for novel targets with novel distractors. Results are discussed in terms
      of attentional explanations of latent inhibition (LI) and perceptual learning and
      of visual search phenomena, such as novel popout. LI, previously attributed only
      to a deficit in the stimulus preexposed group, may also be due to enhanced
      performance in the nonpreexposed group.

PMID- 9157183
TI  - Orienting attention without awareness.
AB  - Previous research has shown that visual attention can be directed to a spatial
      location in 2 qualitatively different ways. Attention can be allocated
      endogenously in response to centrally presented precues, or it can be captured
      exogenously by a visual stimulus with an abrupt onset. It has been suggested that
      exogenous orienting of attention is an automatic process, whereas endogenous
      orienting of attention represents a controlled and strategic process. M.I. Posner
      and C.R.R. Snyder (1975) suggested that an automatic process occurs without
      intention, does not interfere with other mental processes, and does not
      necessarily give rise to awareness, whereas a controlled process will likely
      interfere with other processes and necessarily requires intention and awareness.
      Three experiments investigated the role of awareness in orienting visual
      attention. Endogenous and exogenous components of orienting attention were placed
      in opposition to each other to assess the automaticity of exogenous orienting by
      examining the potential for brief stimulus events to capture attention in the
      absence of subjective awareness. Results show that an exogenous cue presented
      below a subjective threshold of awareness captured attention automatically and
      without awareness.

PMID- 9157184
TI  - Discrimination of the direction and speed of motion in depth of a monocularly
      visible target from binocular information alone.
AB  - Thresholds for discriminating a monocularly visible object's direction of motion
      in depth and speed of motion in depth were measured using only binocular cues.
      Observers could discriminate the direction of motion in depth while totally
      ignoring speed and discriminate the speed of motion in depth while totally
      ignoring direction. Direction discrimination thresholds were the same for motion
      in depth within the vertical and horizontal meridians, even though a cue to
      trajectory was available for motion within the horizontal meridian that is not
      available for motion within the vertical meridian. Speed discrimination
      thresholds also were the same for motion in depth within the vertical and
      horizontal meridians. For the 3 observers the lowest direction discrimination
      thresholds were 0.14 degree, 0.18 degree, and 0.22 degree (means of horizontal
      and vertical thresholds).

PMID- 9157186
TI  - Perceptual and imaginary mixtures in chemosensation.
AB  - D. Algom and W.S. Cain (1991) reported similar interaction patterns for perceived
      and imaginary mixtures of odorants. However, their experimental design did not
      allow sensitive statistical testing to demonstrate differences between
      conditions. Three experiments on 16 mixtures of sucrose-citric acid mixtures
      yielded significantly different interaction pattern for perceived and imaginary
      mixtures. Inconsistencies in the degrees of suppression in the imaginary
      condition suggested that participants did not base their responses on the
      inspection of a mental image but on incomplete implicit or explicit knowledge of
      sensory interactions. Participants knew the phenomenon of mixture suppression and
      knew that its effects were level dependent, but they were unable to predict the
      exact intensity of a mixture on the basis of the intensities of its unmixed
      components.

PMID- 9157185
TI  - If it's not there, where is it? Locating illusory conjunctions.
AB  - There is evidence that complex objects are decomposed by the visual system into
      features, such as shape and color. Consistent with this theory is the phenomenon
      of illusory conjunctions, which occur when features are incorrectly combined to
      form an illusory object. We analyzed the perceived location of illusory
      conjunctions to study the roles of color and shape in the location of visual
      objects. In Experiments 1 and 2, participants located illusory conjunctions about
      halfway between the veridical locations of the component features. Experiment 3
      showed that the distribution of perceived locations was not the mixture of two
      distributions centered at the 2 feature locations. Experiment 4 replicated these
      results with an identification task rather than a detection task. We concluded
      that the locations of illusory conjunctions were not arbitrary but were
      determined by both constituent shape and color.

PMID- 9157187
TI  - Effects of imagery on vernier acuity under conditions of induced depth.
AB  - Imagery interferes with visual acuity (the "Perky effect") when an image is close
      to a visual target and both the image and the acuity target are located in the
      same depth plane. Whether imagery-induced interference occurs when a mental image
      and a target are separated by induced depth was investigated. Participants
      projects an image in front of or behind a vernier acuity target on a frontal or
      back plan suggested by the panels of an outline cube. A drop in accuracy for the
      target was found when an image was projected in front of, but not behind, the
      target. Thus, induced depth can influence the Perky effect. By contrast, real
      lines interfered with the target regardless of perceived depth plane, which is
      inconsistent with the hypothesis that imagery and perception are equivalent.
      Results support the hypothesis that images interfere with perception only when
      the participant must see through an image to obtain information specifying the
      visual target.

PMID- 9157188
TI  - Evidence of limited capacity and noise reduction with single-element displays in
      the location-cuing paradigm.
AB  - Precuing a location facilitates accuracy of identification of a target at that
      location and reduces noise from other nontarget characters in a multicharacter
      field. In 5 experiments, evidence for facilitation included higher accuracy with
      long precue-target intervals than with short intervals and higher accuracy when a
      precue indicated the correct location than with short intervals and higher
      accuracy when a precue indicated the correct location than when it indicated the
      wrong location. These results were found for each target-mask condition used (1
      target with 1 mask, 1 target with 4 masks, or 1 target and 3 nontargets with 4
      masks) in experienced and inexperienced observers. Evidence for noise reduction
      was found because accuracy was higher in the 1 target-1 mask condition than in
      the other conditions on correctly cued trials with short-cue-target intervals and
      on incorrectly cued trials. Data are related to methodological factors that are
      important to obtaining these effects and to capacity and noise reduction models.

PMID- 9157189
TI  - Cyclic peptides from higher plants. 34. Segetalins G and H, structures and
      estrogen-like activity of cyclic pentapeptides from Vaccaria segetalis.
AB  - Segetalins G and H (1-2) possessing estrogen-like activity are cyclic
      pentapeptides from the seeds of Vaccaria segetalis. Their structures, cyclo(-Gly
      Ala-Lys-Tyr-Val) (1) and cyclo(-Gly-Phe-Ser-Tyr-Arg-) (2), were determined by
      interpretation of spectral data.

PMID- 9157190
TI  - Massetolides A-H, antimycobacterial cyclic depsipeptides produced by two
      pseudomonads isolated from marine habitats.
AB  - Massetolides A-H (1-8), novel cyclic depsipeptides, and the known compound
      viscosin (9) have been isolated from cultures of two Pseudomonas sp. isolated
      from a marine alga and a marine tube worm, respectively. Massetolide A (1) and
      viscosin (9) exhibit in vitro antimicrobial activity against Mycobacterium
      tuberculosis and Mycobacterium avium-intracellulare. Precursor-directed
      biosynthesis has been used to generate unnatural massetolides 11-13 incorporating
      nonprotein amino acids.

PMID- 9157191
TI  - Histamine-release effectors from Angelica dahurica var. dahurica root.
AB  - Six compounds isolated from the EtOAc fraction of the dried roots of Angelica
      dahurica var. dahurica inhibited compound 48/80-induced histamine levels in mouse
      peritoneal cavity (in vivo). Bergapten, oxypeucedanin hydrate, and byakangelicin
      inhibited compound 48/80-induced histamine elevation at a dose of 25 mg/kg.
      Conversely, sec-O-acetylbyakangelicin [8-(2-acetoxy-3-hydroxy-3-methylbutoxy)-5
      methoxypsoralenI enhanced compound 48/80-induced histamine elevation at a dose of
      25 mg/kg, while phellopterin and oxypeucedanin had no effect.

PMID- 9157192
TI  - (+)-Angchibangkine, a new type of bisbenzylisoquinoline alkaloid, and other
      dimers from Pachygone dasycarpa.
AB  - Analysis of the alkaloidal fraction of the stem bark extract of Pachygone
      dasycarpa (Menispermaceae) resulted in the isolation of 10 known
      bisbenzylisoquinolines, (+)-tetrandrine, (+)-penduline, (+)-fangchinoline, (+)
      atherospermoline, (+)-N-methyl-7-O-demethylpeinamine, (+)-daphnoline, (4-)
      isotrilobine (1), (+)-cocsuline (2), (+)-tricordatine (3), (+)-2'-norcocsuline,
      and the new alkaloid (+)-12-O-methyltricordatine (4). The last
      bisbenzylisoquinoline alkaloid isolated, (+)-angchibangkine (5), is the first
      member of this alkaloid class found to possess three diphenyl ether bridges in
      the 7-6',8-7', and 11-12' positions. Structure elucidation of these alkaloids and
      of (+)-O-methylangchibangkine (6) was achieved by analysis of spectral data.
      Compounds 4-6 show antiplasmodial activity against Plasmodium falciparum.

PMID- 9157193
TI  - Daleformis, a new phytoalexin from the roots fo Dalea filiciformis: an inhibitor
      of endothelin converting enzyme.
AB  - As part of a search for novel inhibitors of endothelin converting enzyme (ECE),
      the MeOH-CH2Cl2 extract of the roots of Dalea filiciformis was shown to be
      active. Bioassay-guided fractionation of the extract yielded a novel phytoalexin,
      daleformis (1), whose structure was determined by interpretation of spectral data
      and X-ray analysis. Daleformis (1) inhibited ECE with an IC50 of 9 microM.

PMID- 9157194
TI  - Fagomine isomers and glycosides from Xanthocercis zambesiaca.
AB  - 50% aqueous MeOH extracts from the leaves and roots of Xanthocercis zambesiaca
      (Leguminosae) were subjected to various ion-exchange column chromatographic steps
      to give fagomine (1), 3-epi-fagomine (2), 3,4-di-epi-fagomine (3), 3-O-beta-D
      glucopyranosylfagomine (4), and 4-O-beta-D-glucopyranosylfagomine (5). Their
      structures were determined by spectroscopic analyses, particularly by extensive
      1D and 2D NMR studies. Compounds 3 and 4 are new natural products. Compound 1 is
      a good inhibitor of isomaltase and certain alpha- and beta-galactosidases.
      Whereas 2 is a more potent inhibitor of isomaltase and beta-galactosidases than
      1, it does not inhibit alpha-galactosidase. Compounds 3-5 exhibited no
      significant inhibition against the glycosidases used.

PMID- 9157195
TI  - Health care in the United States is undergoing drastic changes attributable in
      large part to the financial crisis in health care funding.

PMID- 9157196
TI  - Regulation of neurotransmission in the arcuate nucleus of the rat by different
      neuropeptide Y receptors.
AB  - We examined the effects of peptides of the neuropeptide Y (NPY)/pancreatic
      polypeptide (PP) family on synaptic transmission in the arcuate nucleus in rat
      hypothalamic slices. Application of NPY produced two effects. In some cells NPY
      produced an outward current that had the properties of a K+ current. NPY also
      inhibited the evoked glutamatergic EPSC recorded in these arcuate neurons by a
      presynaptic mechanism. Although the effects of NPY on the K+ current reversed
      within a few minutes of washout of the peptide, its effects on the EPSC
      frequently were longer lasting (>30 min). Similar effects were observed using
      peptide YY or the NPY analog [Leu31, Pro34]NPY. Although K+ current activation by
      [Leu31,Pro34]NPY was blocked by the selective Y1 antagonist BIBP 3226, inhibition
      of the EPSC was blocked only partially. Other NPY-related peptides such as NPY(13
      36), PP, and [D-Trp32]NPY also inhibited the EPSC. However, none of these
      peptides produced activation of the K+ current. Thus, activation of more than one
      NPY receptor produces synaptic inhibition in the arcuate nucleus. A Y1 receptor
      activates a K+ current postsynaptically, and several receptor types appear to
      inhibit the EPSC by a presynaptic mechanism.

PMID- 9157197
TI  - Negative feedback neuroendocrine control of inflammatory response in the rat is
      dependent on the sympathetic postganglionic neuron.
AB  - Negative feedback control of inflammation is mediated by activation of
      nociceptive afferents that in turn activates the hypothalamic-pituitary-adrenal
      axis to release corticosteroids. Plasma extravasation (PE) produced by the potent
      inflammatory mediator, bradykinin (BK), but not that induced by another potent
      inflammatory mediator, platelet-activating factor (PAF), is inhibited by released
      corticosterone. Because bradykinin, but not PAF, produces PE by a mechanism that
      is, in part, dependent on the sympathetic postganglionic neuron (SPGN) terminal,
      we tested the hypothesis that the negative feedback control of inflammation is
      dependent on the SPGN terminal in the inflamed tissue. In sympathectomized rats,
      the residual (i.e., SPGN-independent) PE in the knee joint produced by BK was not
      inhibited by noxious electrical stimulation. Furthermore, intravenous
      administration of corticosterone potently inhibited, with a similar time-course,
      the SPGN-dependent, but not the SPGN-independent, component of BK-induced PE.
      Neither electrical stimulation nor corticosterone inhibited PAF-induced PE.
      Finally, corticosterone's actions do not appear to be mediated by release of
      norepinephrine from the SPGN terminal, because neither the alpha-adrenergic
      receptor antagonist phentolamine nor the beta2-adrenergic receptor antagonist ICI
      118, 551 antagonized the inhibition of BK-induced PE by corticosterone. We
      conclude that in the rat knee joint, negative feedback control of the
      inflammatory response is dependent on the presence of the SPGN terminal. Further,
      our data suggest that a significant component of corticosteroid-induced
      inhibition of PE produced by inflammatory mediators is SPGN-dependent.

PMID- 9157198
TI  - [Ethics and interventional neuroradiology].

PMID- 9157199
TI  - [MRI and drug-resistant partial epilepsy. What protocol and why? Experiences of
      the Department of Neuroradiology of the Pite-Salpetriere Group Practice
      Hospital].

PMID- 9157200
TI  - [What is your diagnosis? Carbon monoxide poisoning].

PMID- 9157201
TI  - [Magnetic resonance imaging of the olfactory pathways in Kallmann de Morsier
      syndrome].
AB  - INTRODUCTION: Kallmann syndrome is a disease clinically characterized by the
      association of hypogonadotrophic hypogonadism and anosmia or hyposmia. Most cases
      have been recorded among men. It is a genetic disorder with a specific gene
      location on the X chromosome. The cells that normally express luteinizing hormone
      releasing hormone or LHRH fail to migrate the olfactory placode to the forebrain.
      The lateral projections of the olfactory placode also fail to induce development
      of the olfactory bulbs and tracts. MATERIAL AND METHODS: The aim of this study
      was to compare the MRI appearance of the olfactory sulci, the olfactory bulbs and
      frontal lobe between groups. The first reference group was composed of 20
      subjects and the second group of 18 patients suffering from Kallmann syndrome.
      For all studies we used a 1.5 T magnet system (Signa GE). We performed two
      sagittal and coronal T1-weighted sequences in spin echo (TR = 600 ms, TE = 12 ms)
      with interleaved 3 mm slices and a 14 cm field of view. RESULTS: In the first
      group, the two olfactory bulbs were always seen on coronal slices just behind the
      crista galli measuring 2 to 3.2 mm transversally. On sagittal slices, in 60% of
      the cases two bulbs were seen (3 mm laterally of the pituitary stalk) and in the
      other 40% only one bulb was seen. The length of the bulb has been measured
      between 6 and 11 mm. We noticed a plat frontal lobe in 85% of the cases. In the
      second group the olfactory bulbs were never visible among the 18 patients
      suffering from Kallmann syndrome. The hypoplasic sulci were hardly visible and
      their size was less or equal to 1 cm and the frontal lobe was triangular in 80%
      of the cases. One patient had hypoplasia of corpus callosum. CONCLUSION: MRI is
      helpful tool to demonstrate abnormalities of the olfactory system which are
      always present among patients suffering from Kallmann syndrome. MRI can also
      show, at the same time, a possible associated brain abnormality.

PMID- 9157202
TI  - [Lumbar interapophyseal septic arthritis. Apropos of 3 cases].
AB  - Septic arthritis of spinal apophyseal joint, seldom described, mainly concern the
      lumbar spine. We report three cases. Inflammatory lesions of the paravertebral
      soft tissues were associated in each case; an epidural abscess was present twice.
      Our three cases were due to Staphylococcus aureus. The initial clinical features
      were consistent with a spondylodiscitis. Imaging led to the correct diagnosis in
      all cases. According to our observations and several others of the literature:
      facet joint lesions are visible too late on plain films. Bone scintigraphy is
      sensitive, but not specific. CT scan and MRI are the most contributive
      investigations. A pathologic aspect of the paravertebral soft tissues is visible
      less than one week after the beginning of the symptoms on CT scan and MRI.
      Lesions of the facet joint are detectable as soon as the first week on MRI, and
      after 15 days of clinical course on CT scan. Epidural abscess, when present, is
      best shown by MRI as early as the first week. CT scan can guide percutaneous
      needle biopsies of the paravertebral abscesses or of the concerned facet joint.

PMID- 9157203
TI  - 4th Annual winter workshop and annual meeting of the Canadian Rheumatology
      Association. Lake Louise, Alberta, Canada, February 22-24, 1996. Abstracts.

PMID- 9157204
TI  - Stroke management project shows findings.

PMID- 9157205
TI  - Pedestrian pelvic fractures: 5-year experience of a major urban trauma center.
AB  - BACKGROUND: Pedestrian injury accounts for approximately 14% of all vehicular
      associated mortality. We performed a retrospective review of 1,014 injured
      pedestrians admitted to our statewide trauma center between January 1, 1990, and
      December 31, 1994, to determine the pattern and severity of pelvic injury in
      injured pedestrians, the types of associated injuries relative to those pelvic
      injury patterns, and the relationship between pelvic fracture treatment
      modalities and patient outcome. METHODS: Approximately 11% (111 of 1,014) of the
      patients had high-energy pelvic ring disruptions. The average age of these 57 men
      and 54 women was 39.4 years. The average admission Injury Severity Score and
      Glasgow Coma Scale values were 29.2 and 11.7, respectively. Pelvic injuries were
      classified according to the mechanism of injury: lateral compression,
      anteroposterior compression, vertical shear, and combined mechanical injury
      fractures. We compared the mean Glasgow Coma Scale scores, blood utilization,
      number of associated injuries, and mortality rate for each classification.
      RESULTS: Associated trauma included neurologic (30 of 111, 27.0%), thoracic (29
      of 111, 26.1%), and abdominal injury (16 of 111, 14.4%). Overall blood product
      utilization averaged 1,971 mL within the first 24 hours and overall mortality was
      26 of 111 (23.4%). There were 79 (71.2%) lateral compression, 23 (20.7%)
      anteroposterior compression, six (5.4%) vertical shear, and three (2.7%) combined
      mechanical injury fractures. As the severity of lateral compression and
      anteroposterior compression pelvic fractures increased, Glasgow Coma Scale scores
      decreased and Injury Severity Score values, blood utilization, number of
      associated injuries, and mortality rate increased. The highest mortality rate
      (50%) was associated with the most severe (grade III) lateral compression and
      anteroposterior compression injuries. Of particular interest, was the difference
      in the 24-hour blood utilization and mortality rates for patients with lateral
      compression type II pelvic fractures treated before (nonoperative management) and
      after (early external fixation) 1993: 4,760 versus 1,375 mL of blood and 36.4
      versus 12.5% mortality rate, respectively. CONCLUSIONS: In conclusion, pelvic
      fracture appears to be a substantial factor in pedestrian morbidity and
      mortality. Although most pedestrian morbidity and mortality is not caused by the
      intrinsic nature of the pelvic fracture, the severity of these injuries is
      correlated with the degree of destructive energy imparted to the body as a whole,
      as manifested by the number and severity of associated injuries and the mortality
      rate.

PMID- 9157206
TI  - [Milk in our diet: pro and con. Alternative prophylactic measures].

PMID- 9157207
TI  - [Anti-endothelial antibodies and defects of heart valves in antiphospholipid
      syndrome: analysis of pathogenic mechanisms].

PMID- 9157208
TI  - [Geomagnetic field effects on circadian variability of cardiac rhythm].
AB  - To study the effect of geomagnetic field (GMF) on circadian rhythm of the heart
      the author has examined 23 healthy children aged 5-16 years (mean age 12 +/-
      4.8). All the examinees have undergone 24-h Holter monitoring with assessment of
      circadian fluctuations n cardiac rhythm variability (CRV). The data obtained on
      the parameters Mean, SDNN, SDNN = i, SDANN = i, rMSSD and pNN50 were compared to
      circadian fluctuations of 3-h indices GMF Ap-index in the test day with
      estimation of paired correlation index (r). Positive and negative relations
      between CRV and GMF changes were found in 6 and 8 children, respectively. Groups
      of GMF-sensitive and GMF-negative children were formed. At 10-year follow-up 3 of
      7 GMF-sensitive and 6 of 9 GMF-resistant children developed nonspecific diseases.
      It is suggested that GMF may have a synchronizing effect on cardiac circadian
      rhythm. The response of cardiac rhythm to fluctuations of GMF is thought an
      individual chronotype of the body. GMF-resistant group is characterized by self
      regulation of cardiac rhythm which determines reduced availability of exogenic
      synchronizing effects of GMF.

PMID- 9157209
TI  - [Changes in cardiovascular function of ischemic heart disease patients on the
      course of rehabilitation at low-mountain health resort after surgical
      revascularization of myocardium].
AB  - Sanatorium treatment at low-mountain resort of IHD-patients subjected to surgical
      revascularization brought an increase in exercise tolerance, a positive trend in
      ECG parameters, improvement in left ventricular myocardial contractility. The
      benefit is especially pronounced in patients with IHD of functional class I, II
      and normal contractility of the left ventricular myocardium.

PMID- 9157210
TI  - [Intracranial electrical stimulation in the treatment of neurocirculatory
      asthenia and essential hypertension].
AB  - The treatment of neurocirculatory asthenia and essential hypertension stage I and
      II with low-frequency bioresonance intracranial electrostimulation (BIES)
      performed on portable two-channel unit SEM-02 led to uneventful sthenic
      condition, relief of headache, improved sleep and performance, exercise
      tolerance. The quality of the bioenergetic field advanced in all the patients.
      Low-energy BIES may be used in many diseases, provides fast therapeutic effect in
      minimal intake of drugs, is nontoxic and hypoallergic. The unit SEM-02 proved 2.6
      and 1.41 times more effective than similar domestic and foreign equipment,
      respectively.

PMID- 9157211
TI  - [Effect of oxygen in different concentrations and free radical-anti-radical
      activity system in patients with chronic pulmonary insufficiency].
AB  - The study of free-radical processes elucidated concentrations of O2 producing a
      negative effect in chronic obstructive bronchitis sufferers with respiratory
      insufficiency (RI). In RI of the second and third degree concentration of inhaled
      O2 should not exceed 50%. In this concentration O2 toxicity is not evident,
      unbalance of the system free radical-antiradical activity is less pronounced, O2
      transport from the lungs to the tissue reaches optimal level. A course of oxygen
      therapy (20 daily sessions lasting 30 min., 50% O2) is not toxic, promoted
      activation of SOD and alleviation of arterial hypoxemia.

PMID- 9157212
TI  - [The results of combined acupuncture and laser therapy of outpatients with
      duodenal ulcer].
AB  - Exacerbations of duodenal ulcer (DU) were treated outpatient in 130 DU sufferers
      who failed previous chemotherapy. The treatment consisted of acupuncture, laser
      therapy, diet and drugs. All the patients achieved remission, relief of
      vegetative disorders. DU healing took less time (by 7-10 days) than in control
      group. Application of the acupuncture and laser radiation allowed assignment of
      minimal drug doses. 3-year long-term results showed the absence of recurrences
      for 1-3 years. 87 DU patients gave up smoking after additional acupuncture
      according to the special regimen. The conclusion is made that acupuncture
      combined with laser therapy is effective against DU, safe and usable in
      outpatient setting.

PMID- 9157213
TI  - [The importance of transesophageal cardiac pacing in general hospital].
AB  - Diagnostic capacity of transesophageal cardiac pacing (TECP) and bicycle exercise
      (BE) were compared by the data gained in the department of functional diagnosis
      of Tyumen Regional Hospital for 1995. A total of 293 TECP and 642 BE were
      performed for IHD diagnosis and estimation of the functional class. The value of
      TECP grows when coronary pathology is a concomitant disease.

PMID- 9157214
TI  - [Factors influencing the results of chronic glomerulonephritis treatment].
AB  - The effectiveness of different treatment programs was studied in correlation with
      clinical characteristics of chronic glomerulonephritis (CGN) in 665 patients. It
      was established that the higher was CGN activity, the poorer were the treatment
      results. Nephrotic syndrome also had negative implications. The best response was
      brought by prolonged (1-2.5 years) course of corticosteroids and cytostatics.

PMID- 9157215
TI  - [Non-enzyme cation proteins of peripheral blood leukocytes-factor of nonspecific
      reaction of body to injury].

PMID- 9157216
TI  - [Lipid peroxidation and antioxidant defense in renal affections of exotoxic
      etiology].
AB  - Exogenic poisoning is often complicated by toxic nephropathy pathogenesis of
      which remains obscure. In view of this, the authors have performed a clinical
      study of lipid peroxidation (LPO) and antioxidant defense (AOD) in acute exogenic
      poisoning with renal lesion. Acute poisoning results in LPO activation and
      inhibition of AOD enzymes activity. Emerging toxic nephropathy aggravates
      disorders in the system LPO-AOD actively participating in pathogenesis of this
      complication.

PMID- 9157217
TI  - [Concurrent systemic pathology in gynecologic patients with toxoplasmic
      infection].
AB  - A group of gynecologic patients seropositive for toxoplasmosis (244 cases) was
      statistically compared with a group of gynecological patients with the same
      disease but seronegative for toxoplasmosis in respect to the prevalence of
      concurrent systemic pathology, hematologic parameters and immunologic status. It
      was found that chronic acquired toxoplasmosis with prevailing gynecologic
      pathology is accompanied by concurrent systemic pathology characteristic for this
      disease: adynamia, subfebrile condition, lymphadenitis, myocardiopathy,
      encephalopathy and eye pathology; seropositive for toxoplasmosis women
      significantly more often show a decrease in hemoglobin, lymphocytosis or
      lymphopenia, monocytopenia and eosinophilia; secondary immunologic deficiency and
      multiple allergy to medicines are characteristic for chronic acquired
      toxoplasmosis.

PMID- 9157218
TI  - [Neopterin: marker of cellular immunity activation in idiopathic inflammatory
      myopathy].

PMID- 9157219
TI  - [Clinical picture of some diseases in HIV-infected Ethiopians].
AB  - 238 Ethiopians with different diseases have been examined for HIV antibodies. HIV
      infection was found in 167 of them. HIV infection seems to have changed symptoms
      and severity of other diseases. Special clinical signs were established enabling
      the physicians to suspect HIV infection prior to laboratory verification.

PMID- 9157220
TI  - [Secondary amyloidosis as possible complication of psoriasis].

PMID- 9157221
TI  - [13-year follow-up of a male patient with desquamative interstitial pneumonia].

PMID- 9157222
TI  - [Present-day infectious endocarditis].

PMID- 9157223
TI  - [Etiological structure of respiratory virus diseases and modern therapeutic
      opportunities].

PMID- 9157224
TI  - [Cyanosis].

PMID- 9157225
TI  - [The role of "passing processes": is it disease or not?].

PMID- 9157226
TI  - Allen Roses:"enfant terrible" of Alzheimer's research.

PMID- 9157227
TI  - [A method for systematic internal quality assurance in surgery].
AB  - Between April 1993 and December 1996, the data of 3183 patients were recorded and
      analyzed in a program for internal quality assurance at the Department of General
      and Abdominal Surgery of the University of Mainz. The measuring of perioperative
      risk, the finding of intraoperative influences and the objective rating of
      quality of treatment were achieved by means of eight different operation-specific
      documentation sheets and the data records of the operation theater. With our
      system it is possible to measure differences between several surgeons and also
      differences in comparison to national and international results. By means of
      prospective collection of patient data and the built-in control mechanisms we
      obtain a lot of exact and nearly complete data. The information gained not only
      reflects the performance of a department, but can also be used as an instrument
      for the planning of work and deduction. Through optimized therapy the program can
      lead to an improvement of quality.

PMID- 9157228
TI  - [Long-term results of abdominal surgery interventions. Different evaluation from
      the viewpoint of the patient, the surgeon and the public health office].
AB  - The patient, the surgeon and the public health officer (Versorgungsamt) assess
      the long-term results of abdominal operations differently. We tried to
      objectivize these different assessments. The clinical data were collected
      retrospectively. Data on postoperative subjective state and degree of handicap
      were obtained in a written patient survey (March 1995). Two groups with benign
      diseases and one group with malignant disease were examined: 59 patients who had
      undergone sigmoidectomy for diverticulitis (30 female and 29 male patients,
      median age: 61.5 years), 347 patients subjected to proximal gastric vagotomy for
      duodenal ulcers (72 female and 275 male patients, median age: 46 years) and 158
      patients who had undergone gastrectomy for gastric carcinoma (56 patients female,
      102 patients male, median age: 61 years). The public health officer, classed
      35.6% of the patients who had undergone sigmoidectomy and 34.6% of the patients
      who underwent vagotomy as officially handicapped with a stated grade of
      disablement, 77.2% of the patients with gastrectomy were officially classed as
      handicapped. When other diseases were taken into account in addition, 27.1% of
      the patients who had undergone sigmoidectomy, 27.4% of those who had undergone
      vagotomy and 75.9% of the patients with gastrectomy had received passes
      officially identifying them as severely handicapped persons. In the vast majority
      of cases, the combination of several different ailments had resulted in
      recognition of a graded handicap and severely disabled person's pass, skeletal,
      cardiac and circulatory ailments being the most frequent. In spite of this, the
      evaluation of post-operative course by our patients, the surgeon and the public
      health officer (as reflected in the official state classification) in terms of
      the degree of handicap clearly differed.

PMID- 9157229
TI  - [Aspects relevant for abdominal surgery of attempted suicide].
AB  - In this retrospective study of 24 patients who were treated at our clinic during
      the last 22 years after having attempted suicide, we evaluated aspects concerning
      abdominal- and transplantation surgery. There was a predominance of "hard" (70%)
      versus "soft" (30%) methods for suicide attempt. Intra-abdominal injuries
      resulting from attempted suicide by stabbing or shooting should lead to
      laparotomy-the prognosis is then good. Surgical treatment after intoxication,
      especially caustic ingestion, depends on endoscopic and clinical findings. The
      highly increased rates of suicide in patients with end-stage renal disease can be
      reduced significantly by kidney transplantation. The risk of suicide after
      transplantation is further diminished with improved immunosuppressive treatment.
      Only in a few cases there is an indication for liver transplantation-in some
      cases of fulminant hepatic failure caused by self-administered paracetamol
      overdose. Auxiliary liver transplantation may then be considered.

PMID- 9157230
TI  - [Behavior of postoperative adhesions after intraperitoneal administration of
      fibrinolytic drugs in a rat model].
AB  - In a rat model, the effect of the intraperitoneal application of fibrinolytic
      agents on the development of adhesions was examined. Streptokinase and TPA
      reduced sero-serosal adhesions significantly, whereas urokinase did not reduce
      them. Intravascular coagulation was not affected.

PMID- 9157231
TI  - [Bilateral laparoscopic transperitoneal adrenalectomy in pheochromocytoma].
AB  - Laparoscopic transperitoneal and endoscopic extraperitoneal adrenalectomy are two
      safe options in minimally invasive surgery associated with a very low morbidity.
      Comparative studies with the conventional access to the adrenal gland
      demonstrated the advantages of the endoscopic technique. The anterior
      transperitoneal approach yields a better exposure of the anatomic structures and
      allows the surgeon to orient himself more easily, while at the same time he may
      perform additional laparoscopic maneuvers. In two cases of bilateral
      pheochromocytoma a bilateral laparoscopic adrenalectomy was performed
      simultaneously by employing the transperitoneal approach. The duration of surgery
      was approximately 210 and 270 min, respectively, with an intraoperative blood
      loss of about 350 and 400 ml. There were no complications following this
      procedure. Already on the 1st postoperative day, the patients could be fully
      mobilized. Furthermore, immunological data obtained perioperatively support the
      minimal invasiveness of this technique.

PMID- 9157232
TI  - [Long-term outcome after reconstructive interventions of the aorto-iliac
      segment].
AB  - From September 1985 to February 1994, 183 patients (arterial occlusive disease n
      = 108, abdominal aneurysm n = 75) underwent reconstruction of the abdominal
      aorta. In 120 patients an aorto-bi-iliac or aorto-bi-femoral reconstruction was
      performed and in 63 patients a tube-type reconstruction. The early and late
      postoperative complications are described. The complications were dependent on
      the choice of graft, the distal anastomosis and the preoperative risk factors.
      The mortality from elective repairs was compared with the mortality in emergency
      repairs. The role of endovascular reconstructive surgery in comparison to
      conventional reconstructive procedures is discussed.

PMID- 9157233
TI  - [Removal of the small intestine in autologous jejunum transplantation for
      reconstruction of the mouth cavity is a secondary intervention with few
      complications].
AB  - Reconstruction after radical tumor resection in the oropharyngeal region still
      represents an interdisciplinary challenge. Autotransplantation of the jejunum is
      a popular procedure, in which the abdominal surgeon's main task is that of
      harvesting enteral tissue. To evaluate this technique, a careful analysis of
      accompanying perioperative abdominal complications was performed. Additionally,
      we reexamined 35 of 66 patients still living after a follow-up period of 21
      (range 2-63) months on average. The perioperative mortality of 90 patients
      treated for oropharyngeal malignancy using the described procedure was 7.8%. None
      of the perioperative deaths was caused by an abdominal complication associated
      with enteral resection. One abdominal reoperation was performed because of
      abdominal wall dehiscence. For reasons not related to enteral resection, four
      further patients had to be relaparotomized, two of them during their hospital
      stay and two after leaving hospital. In five cases we observed minor
      complications which could be treated nonsurgically. In the follow-up
      reexamination we detected no abdominal late-onset complication except small
      incisional hernias in six cases. Finally, we concluded that despite an elevated
      overall operative risk in this population, complications owing to jejunal
      resection were comparably low. The data regarding the rate of complications
      classify jejunal resection as a safe procedure for reconstructive purposes in
      patients suffering from oropharyngeal malignancy.

PMID- 9157234
TI  - [Intraoperative (hyperthermic) intraperitoneal chemotherapy--considerations and
      aspects of safe intra- and postoperative treatment with cytostatic drugs].
AB  - The application of open intraoperative intraperitoneal chemotherapy following
      cytoreductive surgery for the treatment of pseudomyxoma peritonei or peritoneal
      carcinomatosis requires safety precautions for the medical and non-medical
      personnel. In agreement with already existing rules, precautions were established
      which result in an optimum of safety. These concern the preparation of the
      cytostatic drugs, the application in the operating room as well as personal
      precautions intra- and postoperatively. After the establishment of theses
      recommendations, 22 patients were treated with open intraperitoneal chemotherapy
      in 1.5 years without any severe accidents. Therefore, a safe intraoperative use
      of cytotoxic drugs is possible. At the moment, the indication for such an
      approach may be given in peritoneal carcinomatosis from appendix, colon or
      ovarian cancer. In the future, an adjuvant application in other gastrointestinal
      malignancies (e.g. T3/T4 gastric carcinoma) may be considered.

PMID- 9157235
TI  - Modulation of the surface architecture of gram-negative bacteria by the action of
      surface polymer:lipid A-core ligase and by determinants of polymer chain length.
AB  - Lipopolysaccharides (LPSs) are complex glycolipids found in the outer membrane of
      Gram-negative bacteria. The lipid A-core component of the LPS molecule provides a
      versatile anchor to which a surface polymer:lipid A-core ligase enzyme can attach
      one or more structurally distinct surface polymers in a single bacterial strain.
      In some cases the same polymer can be found on the cell surface in both lipid A
      core-linked and -unlinked forms. Analysis by SDS-PAGE of populations of LPS
      molecules extracted from bacterial cells indicates that there is extensive
      heterogeneity in their size distribution. Much of the heterogeneity results from
      complex modal distributions in the chain length of the polymers which are
      attached to lipid A-core. This is the result of preferential ligation of polymers
      with specific degrees of polymerization during the assembly of the LPS molecule.
      The surface architecture of the Gram-negative bacterial cell is therefore
      profoundly affected by the activities of the surface polymer:lipid A-core ligase
      and by molecular determinants of polymer chain length. Because of the involvement
      of cell-surface polymers in interactions between pathogenic bacteria and their
      hosts, these enzymatic activities also have an important impact on virulence. In
      this review, the organization of LPSs and related surface polymers will be
      described and the current understanding of the molecular mechanisms involved in
      surface diversity will be discussed. Emphasis is placed on the
      Enterobacteriaceae, but similarities to other bacteria suggest that aspects of
      the enterobacterial system will have broader significance.

PMID- 9157236
TI  - RecR is a zinc metalloprotein from Bacillus subtilis 168.
AB  - The Bacillus subtilis RecR protein is required for DNA repair and recombination
      in vivo. In its N-terminal portion, RecR possesses potential zinc-ligand
      structures associated with the multicysteine (C4) superfamily. The number and
      arrangement of the cysteine residues is suggestive of RecR being a zinc-finger
      protein. One of the four cysteines (Cys-60) has been replaced by a Ser (C60S) or
      an Ala (C60A) residue to generate the recR60 and recR601 genes, respectively. B.
      subtilis recR60, recR601 or delta recR1 (a null-mutant allele) cells are 10-, 134
      and 144-fold more sensitive to 10 mM methanesulphonate and 95-, 900- and 1100
      fold more sensitive to the lethal effect of 100 microM 4-nitroquinoline-1-oxide
      (4NQO) than the wild-type strain, respectively. The RecR zinc-ligand C4 motif
      does not seem to be accessible, because the protein is highly resistant to
      oxidation and moderately resistant to reduction. We have determined by different
      biochemical methods that RecR is a zinc metalloprotein whose cysteine residues
      have a structural and/or functional role.

PMID- 9157237
TI  - Integration host factor is a transcriptional cofactor of pilE in Neisseria
      gonorrhoeae.
AB  - Integration host factor (IHF) is a small, heterodimeric DNA-binding protein with
      pleiotropic function. IHF was purified to apparent homogeneity from Neisseria
      gonorrhoeae. Gel-retardation assays demonstrated binding of IHF to the pilE
      promoter region. The IHF-binding site was identified by DNase I protection assays
      and mapped proximal to three previously defined pilE promoters. Removal of the
      putative IHF-binding domain from pilE promoter DNA negated retardation of the DNA
      fragment when assessed by gel-shift analysis. Kleinschmidt electron microscopy
      showed pronounced kinking of pilE promoter DNA following incubation with IHF.
      Isogenic N. gonorrhoeae strains were constructed that contained either a wild
      type pilE locus or a deleted pilE locus where the IHF-binding domain was removed.
      Primer-extension analysis and Northern blotting of total gonococcal RNA showed
      that in the absence of IHF binding at the pilE promoter, transcription was
      reduced 10-fold. Together, these data indicate that IHF is a transcriptional co
      activator of pilE.

PMID- 9157239
TI  - The dual role of Apl in prophage induction of coliphage 186.
AB  - In the present study we show that the Apl protein of the temperate coliphage 186
      combines, in one protein, the activities of the coliphage lambda proteins Cro and
      Xis. We have shown previously that Apl represses both the lysogenic promoter, pL,
      and the major lytic promoter, pR, and is required for excision of the prophage.
      Apl binds at two locations on the phage chromosome, i.e. between pR and pL and at
      the phage-attachment site. Using an in vivo recombination assay, we now show that
      the role of Apl in excision is in the process itself and is not simply a
      consequence of repression of pR or pL. To study the repressive role of Apl at the
      switch promoters we isolated Apl-resistant operator mutants and used them to
      demonstrate a requirement for Apl in the efficient derepression of the lysogenic
      promoter during prophage induction. We conclude that Apl is both an excisionase
      and transcriptional repressor.

PMID- 9157238
TI  - PilP, a pilus biogenesis lipoprotein in Neisseria gonorrhoeae, affects expression
      of PilQ as a high-molecular-mass multimer.
AB  - Studies of gonococcal pilus biogenesis are fundamental to understanding organelle
      structure/function relationships and identifying new approaches to controlling
      disease. This area of research is also relevant to elucidating the basic
      mechanisms of outer membrane translocation of macromolecules, which requires
      components highly related to those involved in type IV pilus expression. Previous
      studies have shown that products of several ancillary pil genes are required for
      organelle biogenesis but of these only PilQ, a member of the GspD protein family,
      is a component of the outer membrane. DNA sequencing of the region upstream of
      pilQ revealed the presence of two open reading frames (ORFs) whose deduced
      polypeptides shared significant identities with proteins required for pilus
      expression in Pseudomonas aeruginosa and Pseudomonas syringae, the genes for
      which are arrayed upstream of a gene encoding a PilQ homologue. Gonococcal
      mutants bearing transposon insertions in these ORFs were non-piliated and failed
      to express pilus-associated phenotypes, and the corresponding genes were
      designated PilO and pilP. The piliation defects in the mutants could not be
      ascribed to polarity on distal pilQ expression as shown by direct measurement of
      PilQ antigen in those backgrounds and the use of a novel technique to create
      tandem duplications in the gonococcus (Gc) genome. As predicted by the presence
      of a consensus lipoprotein signal sequence, PilP expressed in both Escherichia
      coli and Gc could be labelled with [3H]-palmitic acid. PilP- as well as PilQ-
      mutants shed PilC, a protein which facilitates pilus assembly and is implicated
      in epithelial cell adherence, in a soluble form. Combined with the finding that
      levels of multimerized PiIQ were greatly reduced in PilP- mutants, the results
      suggest that PilP is required for PilQ function and that PilQ and PilC may
      interact during the terminal stages of pilus biogenesis. The findings also
      support the hypothesis that the Gc PilQ multimer corresponds to a physiologically
      relevant form of the protein required for pilus biogenesis.

PMID- 9157240
TI  - The com locus controls genetic transformation in Streptococcus pneumoniae.
AB  - Genetic exchange by natural transformation in Streptococcus pneumoniae occurs in
      a cell-density dependent process and is initiated by a small extracellular
      signalling molecule, the competence-stimulating peptide (CSP). comC, the gene for
      this peptide, has previously been identified and encodes a 44 amino acid pre
      peptide that is apparently processed to an active molecule that consists of the C
      terminal 17 amino acids. We have sequenced the region adjacent to comC and shown
      that it is the first gene of an operon, com, consisting of two downstream
      elements, comD and comE, which encode members of the two-component family of
      sensor regulators. Null mutants with defects in either comC or comD were
      transformation deficient and failed to respond to exogenous CSP. A comC mutant
      did not exhibit any detectable CSP activity, while a comD mutant that contained
      an intact comC produced minimal CSP activity. In mixed-culture experiments
      consisting of isogenic pairs of pneumococci (Csp+ and Csp-), we showed that
      induction of competence by quorum sensing was independent of CSP. Northern
      analysis showed that com was transcribed as a single polycistronic message, while
      analysis of strains with transcriptional fusions showed that com was
      constitutively expressed under conditions that both promoted or repressed the
      development of competence. Finally, we showed genetically and biochemically a CSP
      dependent transcription of rec, a competence-induced locus, and that ComD and
      ComE are required for this CSP-dependent expression.

PMID- 9157241
TI  - Peptidoglycan structure of Salmonella typhimurium growing within cultured
      mammalian cells.
AB  - The cell wall structure of Salmonella typhimurium has been studied for the first
      time during transit from free-living to parasitic lifestyles. Peptidoglycan of S.
      typhimurium proliferating within human epithelial cells contains a high
      proportion of previously unidentified muropeptides (5-10-fold higher than in
      extracellular bacteria). Amino acid and mass-spectrometry analyses showed that
      these new components consist of dimeric cross-linked muropeptides lacking one of
      the two disaccharide (N-acetyl-glucosamine-beta-(1-->4)-N-acetyl-muramic acid)
      molecules. This unique structure suggests an active role for an N-acetyl-muramyl
      L-alanine-amidase in remodelling the peptidoglycan of intracellular S.
      typhimurium. Additional alterations observed included: (i) the absence of glycine
      containing muropeptides; (ii) the increase in the relative proportion of
      muropeptides cross-linked by L(meso)-diaminopimelyl-D(meso)-diaminopimelic acid
      (L-D) peptide bridges; and, (iii) the decrease in the global cross-linkage of the
      macromolecule. The structural alterations observed in the peptidoglycan of
      intracellular bacteria do not produce loss of the cell envelope. These results
      show that intracellular residence of S. typhimurium within epithelial cells is
      accompanied by significant changes in the bacterial cell wall. Remodelling of
      peptidoglycan structure may constitute another sophisticated strategy of this
      pathogen for adapting to and colonizing the intracellular niche of eukaryotic
      cells.

PMID- 9157242
TI  - Integration host factor stimulates both FimB- and FimE-mediated site-specific DNA
      inversion that controls phase variation of type 1 fimbriae expression in
      Escherichia coli.
AB  - The site-specific DNA inversion that controls phase variation of type 1
      fimbriation in E. coli is catalysed by two recombinases, FimB and FimE. Efficient
      inversion by either recombinase also requires the leucine-responsive regulatory
      protein (Lrp). In addition, FimB recombination is stimulated by the integration
      host factor (IHF). The effect of IHF on FimE inversion has not previously been
      reported. Here it is shown that IHF stimulates FimE recombination; In strain
      MG1655, mutants containing lesions in either the alpha (ihfA) or beta (ihfB)
      subunits of IHF show a marked decrease in both FimB- (100-fold) and FimE (15,000
      fold)-promoted switching. IHF is shown to bind with high affinity to sites both
      adjacent to (site I) and within (site II) the fim invertible element.
      Furthermore, mutations in site I or site II that lower the affinity of IHF
      binding In vitro were found to lower the frequency of FimE and/ or FimB
      recombination in vivo. Although site I and site II mutations in combination have
      an effect on FimB-promoted switching comparable to that of IHF knockout mutations
      (100-fold), the cis site mutations have a much less marked effect (100-fold) on
      FimE-promoted switching.

PMID- 9157243
TI  - Bacteriophage T12 of Streptococcus pyogenes integrates into the gene encoding a
      serine tRNA.
AB  - The region of temperate bacteriophage T12 responsible for integration into the
      chromosome of Streptococcus pyogenes has been identified. The integrase gene
      (int) and the phage attachment site (attP) are found immediately upstream of the
      gene for speA, the latter of which is known to be responsible for the production
      of erythrogenic toxin A (also known as pyrogenic exotoxin A). The integrase gene
      has a coding capacity for a protein of 41457 Da, and the C-terminus of the
      deduced protein is similar to other conserved C-terminal regions typical of phage
      integrases. Upstream of int is a second open reading frame, which is capable of
      encoding an acidic protein of 72 amino acids (8744 Da); the position of this
      region in relation to int suggests it to be the phage excisionase gene (xis). The
      arms flanking the integrated prophage (attL and attR) were identified, allowing
      determination of the sequences of the phage (attP) and bacterial (attB)
      attachment sites. A fragment containing the integrase gene and attP was cloned
      into a streptococcal suicide vector; when introduced into S. pyogenes by
      electrotransformation, this plasmid stably integrated into the bacterial
      chromosome at attB. The insertion site for the phage into the S. pyogenes
      chromosome was found to be in the anticodon loop of a putative type II gene for a
      serine tRNA. attP and attB share a region of identity that is 96 bp in length;
      this region of identity corresponds to the 3' end of the tRNA gene such that the
      coding sequence remains intact after integration of the prophage. The symmetry of
      the core region of att may set this region apart from previously described phage
      attachment sites (Campbell, 1992), and may play a role in the biology of this
      medically important bacteriophage.

PMID- 9157244
TI  - The type IC hsd loci of the enterobacteria are flanked by DNA with high homology
      to the phage P1 genome: implications for the evolution and spread of DNA
      restriction systems.
AB  - EcoR124l, EcoDXXl and Ecoprrl are the known members of the type IC family of DNA
      restriction and modification systems. The first three are carried on large,
      conjugative plasmids, while Ecoprrl is chromosomally encoded. The enzymes are
      coded by three genes, hsdR, hsdM and hsdS. Analysis of the DNA sequences upstream
      and downstream of the type IC hsd loci shows that all are highly homologous to
      each other and also to sequences present in the bacteriophage P1 genome. The
      upstream sequences include functional phd and doc genes, which encode an
      addiction system that stabilizes the P1 prophage state, and extend to and beyond
      pac, the site at which phage DNA packaging begins. Downstream of the hsd loci, P1
      DNA sequences begin at exactly the same place for all of the systems. For EcoDXXl
      and Ecoprrl the P1 homology extends for thousands of base pairs while for
      EcoR124l and IS1 insertion and an associated deletion have removed most of the P1
      homologous sequences. The significance of these results for the evolution of DNA
      restriction and modification systems is discussed.

PMID- 9157245
TI  - Molecular characterization of hpuAB, the haemoglobin-haptoglobin-utilization
      operon of Neisseria meningitidis.
AB  - We previously identified HpuB, an 85 kDa Fe-repressible protein required for
      utilization of Fe from, and binding to, haemoglobin and the haemoglobin
      haptoglobin complex. The gene for hpuB was cloned from Neisseria meningitidis
      strain DNM2 and the predicted amino acid sequence indicates that HpuB is an outer
      membrane receptor belonging to the TonB family of high-affinity transport
      proteins. A second open reading frame, predicted to encode a 34.8 kDa
      lipoprotein, was discovered 5' to hpuB, and was designated hpuA. HpuA was
      identified in a total-membrane-protein preparation by construction of a mutant
      lacking HpuA. Acylation of HpuA was confirmed by [3H]-palmitic acid labelling of
      meningococci. Consensus promoter sequences were not apparent 5' to hpuB. The hpuA
      insertion mutation exerted a polar effect, abolishing expression of hpuB,
      suggesting that hpuA and hpuB are co-transcribed. The 3.5 kb polycistronic hpuAB
      mRNA was identified and shown to be transcriptionally repressed by iron. The
      transcriptional start site was identified 33 nucleotides 5' to the hpuA
      translational start site, appropriately positioned around consensus promoter and
      ferric uptake regulator (Fur)-box sequences. The structure of this operon
      suggests that HpuA-HpuB is a two-component receptor analogous to the bipartite
      transferrin receptor TbpB-TbpA.

PMID- 9157246
TI  - Characterization of the locus encoding the Streptococcus pneumoniae type 19F
      capsular polysaccharide biosynthetic pathway.
AB  - We have previously reported the nucleotide sequence of the first six genes of the
      Streptococcus pneumoniae type 19F capsular polysaccharide biosynthesis locus
      (cps19f). In this study we used plasmid insertion/rescue and inverse polymerase
      chain reaction (PCR) to clone an additional 10 kb downstream region containing
      the remainder of the cps19f locus, which was then subjected to sequence analysis.
      The cps19f locus is located in the S. pneumoniae chromosome between dexB and
      aliA, and consists of 15 open reading frames (ORFs), designated cps19fA to
      cps19fO, that appear to be arranged as a single transcriptional unit. Insertion
      duplication mutants in seven out of the nine new ORFs have been constructed in a
      smooth type 19F strain, all of which resulted in a rough (nonencapsulated)
      phenotype, confirming that the operon is essential for capsule production.
      Comparison with sequence databases has allowed us to propose functions for 12 of
      the cps19f gene products, and a biosynthetic pathway for type 19F capsular
      polysaccharide. T7 expression studies confirmed that cps19fH, cps19fK, cps19fL,
      cps19fM and cps19fN directed the production of polypeptides of the expected size
      in Escherichia coli. The function of the cps19fK product was confirmed by its
      ability to complement a mutation in nfrC (rffE) in E. coli, as judged by
      restoration of sensitivity to bacteriophage N4. Interestingly, the last four
      genes of the locus (cps19fL-O) exhibit very strong homology (up to 70% amino acid
      identity) to a portion of the Shigella flexneri rfb gene cluster encoding
      biosynthesis of dTDP-rhamnose. When expressed in E. coli, cps19fL-O were capable
      of complementing a mutation deleting the respective Shigella flexneri homologues.
      Southern hybridization analysis indicated that cps19fA and cps19fB were the only
      cps genes found in all 16 S. pneumoniae serotypes/groups tested. The region from
      cps19fG to cps19fK was found only in members of serogroup 19, and, within this,
      cps19fl was unique to type 19F.

PMID- 9157247
TI  - Regulation of O-antigen chain length is required for Shigella flexneri virulence.
AB  - It is shown that Shigella flexneri maintains genetic control over the modal chain
      length of the O-antigen polysaccharide chains of its lipopolysaccharide (LPS)
      molecules because such a distribution is required for virulence. The effect of
      altering O-antigen chain length on S. flexneri virulence was investigated by
      inserting a kanamycin (Km)-resistance cassette into the rol gene (controlling the
      modal O-antigen chain length distribution), and into the rfbD gene, whose product
      is needed for synthesis of dTDP-rhamnose (the precursor of rhamnose in the O
      antigen). The mutations had the expected effect on LPS structure. The rol::Km
      mutation was impaired in the ability to elicit keratoconjunctivitis, as
      determined by the Sereny test. The rol::Km and rfbD::Km mutations prevented
      plaque formation on HeLa cells, but neither mutation affected the ability of S.
      flexneri to invade and replicate in HeLa cells. Microscopy of bacteria-infected
      HeLa cells stained with fluorescein isothiocyanate (FITC)-phalloidin demonstrated
      that both the rol::Km and rfbD::Km mutants were defective in F-actin tall
      formation: the latter mutant showed distorted F-actin tails. Plasma-membrane
      protrusions were occasionally observed. Investigation of the location of IcsA
      (required for F-actin tail formation) on the cell surface by immunofluorescence
      and immunogold electron microscopy showed that while most rol mutant bacteria
      produced little or no cell-surface IcsA, 10% resembled the parental bacterial
      cell (which had IcsA at one cell pole; the rfbD mutant had IcsA located over its
      entire cell surface although it was more concentrated at one end of the cell).
      That the O-antigen chains of the rol::Km mutant did not mask the IcsA protein was
      demonstrated by using the endorhamnosidase activity of Sf6c phage to digest the O
      antigen chains, and comparing untreated and Sf6c-treated cells by
      immunofluorescence with anti-IcsA serum.

PMID- 9157248
TI  - Bidirectional regulation of two DNA-damage-inducible genes, MAG1 and DDI1, from
      Saccharomyces cerevisiae.
AB  - MAG1 encodes a Saccharomyces cerevisiae 3-methyladenine DNA glycosylase that
      initiates a base-excision-repair pathway and protects yeast cells from killing by
      methylating agents such as methyl methanesulphonate (MMS). In the promoter region
      of the MAG1 gene, there is an 8 bp GC-rich direct repeat (DR). Here we report
      that the DR sequence functions as an upstream activating site (UAS) that
      upregulates the expression of MAG1 as well as another DNA-damage-inducible gene,
      DDI1, which is transcribed divergently from MAG1. Deletions, or point mutations,
      within this repeat completely abolished DNA-damage induction and resulted in a
      reduced basal-level expression for both MAG1 and DDI1 genes. Furthermore, yeast
      cells carrying the MAG1 gene with the DR deletion displayed an increased
      sensitivity to MMS compared with wildtype cells. The DR sequence alone can
      activate transcription of a CYC1 minimal promoter and confer a partial DNA-damage
      responsiveness. Electrophoretic mobility-shift assays indicate that the DR
      function is not due to interaction with the yeast RPA. Like MAG1, the DDI1 gene
      is also controlled by an upstream repressing site (URS) located 5' to the direct
      repeat. Based on this and previous studies, a model is proposed whereby the
      constitutive expression of MAG1 and DDI1 is controlled by two functionally
      opposite regulatory elements, UAS and URS, probably through an antagonistic
      mechanism, whereas the damage-induced expression appears to be regulated by
      mechanisms of derepression at the URS as well as activation at the UAS.

PMID- 9157249
TI  - Construction and analysis of a recombination-deficient (radA) mutant of Haloferax
      volcanii.
AB  - By deleting the radA open reading frame of an extreme halophile, Haloferax
      volcanii, we created and characterized a recombination-deficient archaeon. This
      strain, Hf. volcanii DS52, has no detectable DNA recombination, is more sensitive
      to DNA damage by UV light and ethylmethane sulfonate, and has a slower growth
      rate than the wild type. These characteristics are similar to those observed in
      recombination mutants of Eukarya and Bacteria, and show that the radA gene
      belongs in the recA/RAD51 family by function as well as sequence homology. In
      addition, strain DS52 was not transformable by plasmids pWL102 or pUBP2 (which
      contain pHV2 and pHH1 replicons, respectively), although it was readily
      transformed by plasmids containing a pHK2 replicon, indicating a role for radA in
      the maintenance or replication of some halobacterial plasmids. Despite its slower
      growth rate, Hf. volcanii DS52 was still easy to culture and transform, and
      should be suitable for use in studies where a recombination-deficient background
      is desired.

PMID- 9157250
TI  - Interspecies recombination, and phylogenetic distortions, within the glutamine
      synthetase and shikimate dehydrogenase genes of Neisseria meningitidis and
      commensal Neisseria species.
AB  - Visual inspection showed clear evidence of a history of intraspecies
      recombinational exchanges within the neighbouring meningococcal shikimate
      dehydrogenase (aroE) and glutamine synthetase (glnA) genes, which was supported
      by the non-congruence of the trees constructed from the sequences of these genes
      from different meningococcal strains, and by statistical tests for mosaic
      structure. Many examples were also found of highly localized interspecies
      recombinational exchanges between the meningococcal aroE and glnA genes and those
      of commensal Neisseria species. These exchanges appear to have inflated the
      sequence variation at these loci, and have resulted in major distortions of the
      phylogenetic trees constructed from the sequences of the aroE and glnA genes of
      human pathogenic and commensal Neisseria species. Statistical tests for sequence
      mosaicism, and for anomalies within the Neisseria species trees, strongly
      supported the view that frequent interspecies recombination has occurred within
      aroE and glnA. The high levels of sequence variation, and intra- and interspecies
      recombination, within aroE and glnA did not appear to be due to a 'hitch-hiking'
      effect caused by positive selection for variation at a neighbouring gene. Our
      results suggest that interspecies recombinational exchanges with commensal
      Neisseria occur frequently in some meningococcal 'housekeeping' genes as they can
      be observed readily even when there appears to be no obvious selection for the
      recombinant phenotypes.

PMID- 9157251
TI  - Repetitive sequences found in the chromosome of the myxobacterium Nannocystis
      exedens are similar to msDNA: a possible retrotransposition event in bacteria.
AB  - The first reverse transcriptase (RT) to be found in a prokaryotic cell is encoded
      by an element called a retron which resides in the chromosome of many different
      bacteria. In addition, all retrons code for a functionally obscure RNA-DNA
      satellite molecule called msDNA. msDNA is synthesized from an RNA template by the
      retron-encoded RT. An unusual retron element is described here from the
      myxobacterium Nannocystis exedens. This retron does not appear to have a typical
      RT gene in close proximity (1 kb) to the gene msd (which encodes the DNA strand
      of msDNA). The gene msr (which encodes the RNA strand of msDNA) appears to be
      duplicated and flanks both sides of the msd gene. Also discovered throughout the
      chromosome of this bacterium is a set of repeated sequences related to msDNA.
      These repeat sequences match only part of the sequences of msDNA and may have
      become incorporated into the chromosome of this bacterium by reverse
      transcription.

PMID- 9157252
TI  - Haem iron-transport system in enterohaemorrhagic Escherichia coli O157:H7.
AB  - In this study, we identified the iron-transport systems of Escherichia coli
      O157:H7 strain EDL933. This strain synthesized and transported enterobactin and
      had a ferric citrate transport system but lacked the ability to produce or use
      aerobactin. It used haem and haemoglobin, but not transferrin or lactoferrin, as
      iron sources. We cloned the gene encoding an iron-regulated haem-transport
      protein and showed that this E. coli haem-utilization gene (chuA) encoded a 69
      kDa outer membrane protein that was synthesized in response to iron limitation.
      Expression of this protein in a laboratory strain of E. coli was sufficient for
      utilization of haem or haemoglobin as iron sources. Mutation of the chromosomal
      chuA and tonB genes in E. coli O157:H7 demonstrated that the utilization of
      haemin and haemoglobin was ChuA- and TonB-dependent. Nucleotide sequence analysis
      of chuA revealed features characteristic of TonB-dependent, Fur-regulated, outer
      membrane iron-transport proteins. It was highly homologous to the shuA gene of
      Shigella dysenteriae and less closely related to hemR of Yersinia enterocolitica
      and hmuR of Yersinia pestis. A conserved Fur box was identified upstream of the
      chuA gene, and regulation by Fur was confirmed.

PMID- 9157253
TI  - Transcriptional activation by FNR and CRP: reciprocity of binding-site
      recognition.
AB  - Anaerobic expression of the focA pfl operon is dependent on the transcription
      factors ArcA and FNR and transcription is directed by multiple, anaerobically
      regulated promoters. A FNR-binding site is centred at -41.5 bp relative to the P6
      promoter, inactivation of which severely impairs anaerobic expression of the
      complete operon. Mutations were introduced into this binding site to create a
      consensus recognition site for the cAMP-receptor protein, CRP (CC-site), and one
      that was recognised by both CRP and FNR (CF-site). Transcription directed by
      these mutant binding sites in vivo in different promoter constructs was analysed
      by primer extension and by constructing lacZ operon fusions. With a derivative
      including only the P6 promoter and the CF-binding site, transcription was shown
      to be independent of oxygen and was activated by CRP or FNR. In agreement with
      previous findings, FNR only activated transcription anaerobically. In a construct
      including the CC-binding site transcription was strong. CRP dependent and
      initiated at the identical site to the wild-type promoter. Transcription
      activation from the CC-site was exquisitely sensitive to low cAMP concentration.
      Surprisingly, in a crp mutant, anaerobically inducible, FNR-dependent
      transcription directed by the CC-site was detected, indicating that FNR can
      recognise a consensus CRP-binding site in vivo. A strain unable to synthesise CRP
      or FNR exhibited no transcription from the P6 promoter. Essentially the same
      results were observed in a series of constructs that also included the promoter
      P7 and its regulatory sequences. Evidence is also presented which demonstrates
      that CRP activates transcription from the natural FNR-binding site of the P6
      promoter. In vitro DNA-binding studies showed that CRP specifically interacted
      with the FNR-binding site, protecting exactly the same sequence as that protected
      by the FNR protein. Interaction of CRP with the natural FNR-binding site was
      reduced greater than 50-fold compared to its interaction with the mutant CC
      binding site. Although we could not demonstrate that FNR interacted with the CC
      binding site in vitro, it did bind to the CF-site giving the same protection as
      observed with the wild-type FNR-binding site. FNR also activated transcription
      from the CF-site in vitro, giving further support to the idea that a single
      functional DNA half-site is sufficient to direct binding and transcription
      activation by a dimeric transcription factor.

PMID- 9157254
TI  - Plasmodium falciparum glucose-6-phosphate dehydrogenase (G6PD)-the N-terminal
      portion is homologous to a predicted protein encoded near to G6PD in Haemophilus
      influenzae.

PMID- 9157255
TI  - A new cellulase family.

PMID- 9157256
TI  - 3D electron dose calculation using a Voxel based Monte Carlo algorithm (VMC).
AB  - A new model for calculating electron beam dose has been developed. The algorithm
      is based on a two- or three-dimensional geometry defined by computerized
      tomography (CT) images. The Monte Carlo technique was used to solve the electron
      transport equation. However, in contrast to conventional Monte Carlo models
      (EGS4) several approximations and simplifications in the description of
      elementary electron processes were introduced reducing in this manner the
      computational time by a factor of about 35 without significant loss in accuracy.
      The Monte Carlo computer program does not need any precalculated data. The random
      access memory required is about 16 Mbytes for a 128(2) X 50 matrix, depending on
      the resolution of the CT cube. The Voxel Monte Carlo model (VMC) was tested in
      comparison to calculations by EGS4 and the "Hogstrom algorithm" (MDAH) using
      several fictive phantoms. In all cases a good coincidence has been found between
      EGS4 and VMC, especially near tissue inhomogeneities, whereas the MDAH algorithm
      has produced dose underestimations of up to 40%.

PMID- 9157257
TI  - Electron dose calculation using multiple-scattering theory: a new theory of
      multiple scattering.
AB  - Starting from the Boltzmann-Fokker-Planck transport equation, we have developed a
      new theory of multiple scattering which incorporates the advances already made
      with our Gaussian multiple-scattering theory for electron dose calculation. This
      incorporation has been accomplished in a natural way, by modifying the scattering
      power T and by adding a convolution term to the distribution-function equation of
      the Gaussian theory. Our previous results concerning increasing the accuracy of
      the small-angle approximation used and dealing with localized tissue
      inhomogeneities have thus been maintained, and we have arrived at a complete
      distribution function in both transverse spatial and angular variables. When
      integrated over the transverse angular variables, for a first-order small-angle
      approximation this distribution function for a pencil beam is essentially the
      same as the Moliere multiple-scattering distribution, which includes large-angle
      single scattering. For a water phantom, we have used comparisons with EGS4 Monte
      Carlo calculations to demonstrate the greatly increased accuracy of our new
      multiple-scattering theory over the Gaussian theory, which includes the usual
      Fermi-Eyges theory. We have also presented a fairly accurate Gaussian
      approximation to the pencil-beam dose profiles given by our new theory, which can
      be used in order to maintain the mathematical simplicity of the predictions of
      the Fermi-Eyges theory.

PMID- 9157258
TI  - Superposition dose calculation incorporating Monte Carlo generated electron track
      kernels.
AB  - The superposition/convolution method and the transport of pregenerated Monte
      Carlo electron track data have been combined into the Super-Monte Carlo (SMC)
      method, an accurate 3-D x-ray dose calculation algorithm. The primary dose (dose
      due to electrons ejected by primary photons) is calculated by transporting
      pregenerated (in water) Monte Carlo electron tracks from each primary photon
      interaction site, weighted by the terma for that site. The length of each
      electron step is scaled by the inverse of the density of the medium at the
      beginning of the step. Because the density scaling of the electron tracks is
      performed for each individual transport step, the limitations of the macroscopic
      scaling of kernels (in the superposition algorithm) are overcome. This time
      consuming step-by-step transport is only performed for the primary dose
      calculation, where current superposition methods are most lacking. The scattered
      dose (dose due to electrons set in motion by scattered photons) is calculated by
      superposition. In both a water-lung-water phantom and a two lung-block phantom,
      SMC dose distributions are more consistent with Monte Carlo generated dose
      distributions than are superposition dose distributions, especially for small
      fields and high energies-for an 18-MV, 5 X 5-cm(2) beam, the central axis dose
      discrepancy from Monte Carlo is reduced from 4.5% using superposition to 1.5%
      using SMC. The computation time for this technique is approximately 2 h
      (depending on the simulation history), 20 times slower than superposition, but 15
      times faster than a full Monte Carlo simulation (on our platform).

PMID- 9157259
TI  - Capillary optics for neutron capture therapy.
AB  - The development of capillary neutron optics permits a new technology for neutron
      capture therapy involving the application of a focused thermal neutron beam at
      the medically optimal location within the patient. A subthermal neutron beam
      begins to converge as it travels through a neutron "lens," reaching a narrow
      focus within a tube that allows it to pass directly to the treatment region. This
      technique results in a substantially lower dose to untreated parts of the patient
      and a substantially weaker radiation field in the treatment room generally.
      Additional advantages include the relative ease of thermal neutron generation and
      the ability to shield the patient completely and effectively from fast neutrons
      or gamma rays originating at the neutron source. This work describes the
      application of capillary optics to neutron capture therapy, along with Monte
      Carlo calculations of the neutron flux profiles within a patient for an optimized
      system design. Specific dose profiles for the case of boron neutron capture
      therapy within the brain are also provided.

PMID- 9157260
TI  - Bremsstrahlung production at 50 MeV in different target materials and
      configurations.
AB  - A combination of Monte Carlo, convolution, and experimental techniques have been
      used to investigate bremsstrahlung production at 50 MeV in full-range targets to
      produce narrow elementary photon beams for scanning. Calculations using the ITS
      3.0 Monte Carlo system for various target designs, including particle transport
      through the treatment head of an MM5O racetrack microtron and a water phantom,
      have been compared to experimental dose profiles from narrow photon beams at 10
      cm depth in water. A reduction in the ITS 3.0 default substep size has been found
      necessary even for incomplete agreement, in consistency with the findings of
      Faddegon and Rogers [Nucl. Instrum. Meth. A 327, 556-565 (1993)] for a different
      experimental setup and energy using the previous version of ITS. Results show
      that the calculated shape of the tail of dose distributions from narrow photon
      beams agrees well with measurements, but CYLTRAN/ITS 3.0 fails to reproduce the
      central part of the distribution. The discrepancy at small angles, reported
      previously for EGS4 and ITS 2.1 simulations, possess a limitation to Monte Carlo
      simulations of narrow photon beams used in scanned systems of clinical
      accelerators. Radial dose profiles have been calculated by convolution of the
      energy fluence at the exit of the target with one polyenergetic Monte Carlo
      calculated dose kernel and also a database consisting of ten different dose
      kernels corresponding to different monoenergetic photon pencil beams for
      comparison. The agreement with the much slower fully detailed Monte Carlo
      calculations was better when using the database kernels than the polyenergetic
      kernel. Results for the mean energy, mean polar angle, and energy fluence at
      different depths within various targets have been obtained. These are discussed
      in the context of the design characteristics of bremsstrahlung targets with
      emphasis on their utilization for scanning photon beam techniques.

PMID- 9157261
TI  - Experimental determination of the dose kernel in high-energy x-ray beams.
AB  - A semiempirical method to characterize the pencil-beam dose kernel is presented.
      Results from measurements are described by mathematical models of the applicable
      physical processes. The measurements were made with 6 and 25 MV x-ray beams from
      a linear accelerator. Broad-beam notations were used consistently, and the pencil
      beam quantities were obtained by differentiation. The results were compared to
      pencil-beam kernels calculated by Monte Carlo techniques. The analysis of the
      measured data included a number of approximations. It was assumed that all the
      constituent pencil beams in the field are parallel, i.e., the divergence is
      ignored. Furthermore, the lateral variations of the incident photon fluence and
      the energy spectrum were disregarded. Monte Carlo calculations, on the other
      hand, are based on an average energy spectrum over the field, and are free from
      divergence and variations in the incident photon fluence. Measured and Monte
      Carlo calculated pencil beams nevertheless agreed well, and the approximations
      mentioned caused at maximum 2.7% discrepancies for the largest field size at 6
      MV.

PMID- 9157262
TI  - Use of a micro-ionization chamber and an anthropomorphic head phantom in a
      quality assurance program for stereotactic radiosurgery.
AB  - Quality assurance methods used in association with radiosurgery must include all
      aspects of the radiosurgery process: visualization and localization of the
      target, treatment and dose planning and dose delivery. Presented here is a
      quality assurance method that utilizes an anthromorphic head phantom and a micro
      ionization chamber to demonstrate precise target localization and accurate dose
      delivery. This micro-ionization chamber method offers an immediate readout which
      is both accurate and reproducible. Additionally, this method allows unlimited
      repetition of the dose measurement process without repeated radiographic
      localization studies as is necessary with the conventional methods of TLD, film,
      and Fricke gels. The method and techniques presented can be used in the
      acceptance testing and routine quality assurance of both linac-based and Gamma
      Knife radiosurgery units.

PMID- 9157263
TI  - Output stability of a linear accelerator during the first three seconds.

PMID- 9157264
TI  - Use of routine quality assurance procedures to detect the loss of a linear
      accelerator primary scattering foil.
AB  - The effects of the mechanical loss of a stainless steel primary scattering foil
      on a 12-MeV electron beam from a dedicated intraoperative electron accelerator
      are discussed. Routine quality assurance tests, including dose output constancy,
      energy constancy, and beam uniformity (flatness and symmetry), were used to
      determine the nature of the malfunction when it occurred. It is concluded that
      these quality assurance checks, if done with the frequencies recommended by the
      AAPM Task Group 40 Report [Med. Phys. 21, 581-619 (1994)] and repeated at the
      time of occurrence, are sufficient to detect loss of an electron scattering foil.

PMID- 9157265
TI  - Use of simple quality assurance procedures in the analysis of beam asymmetries on
      cobalt-60 treatment units.
AB  - Recently, the mechanical failure of one of the upper collimator mechanical
      trimmers on a cobalt-60 unit resulted in large beam asymmetries and unacceptable
      flatness characteristics. This malfunction was not detected using currently
      accepted schedules for quality assurance tests. The incident suggests that the
      frequency of routine beam profile constancy checks should be increased to weekly
      for cobalt-60 units.

PMID- 9157266
TI  - Calculation of portal dose using the convolution/superposition method.
AB  - The convolution/superposition method was used to predict the dose throughout an
      extended volume, which includes a phantom and a portal imaging device. From the
      calculated dose volume, the dose delivered in the portal image plane was
      extracted and compared to a portal dose image. This comparison aids in verifying
      the beam configuration or patient setup after delivery of the radiation. The
      phantoms used to test the accuracy of this method include a solid water cube, a
      Nuclear Associates CT phantom, and an Alderson Rando thorax phantom. The dose
      distribution in the image plane was measured with film and an electronic portal
      imaging device in each case. The calculated portal dose images were within 4% of
      the measured images for most voxels in the central portion of the field for all
      of the extended volumes. The convolution/superposition method also enables the
      determination of the scatter and primary dose contributions using the particular
      dose deposition kernels for each contribution. The ratio of primary dose to total
      dose was used to extract the primary dose from the detected portal image, which
      enhances the megavoltage portal images by removing scatter blurring. By also
      predicting the primary energy fluence, we can find the ratio of computed primary
      energy fluence to total dose. Multiplying this ratio by the measured dose image
      estimates the relative primary energy fluence at the portal imager. The image of
      primary energy fluence possesses higher contrast and may be used for further
      quantitative image processing and dose modeling.

PMID- 9157267
TI  - Measurement and calculation of the dose at large distances from brachytherapy
      sources: Cs-137, Ir-192, and Co-60.
AB  - In a small number of special cases it may be necessary to estimate the radiation
      dose to organs far away from the target volume of a patient receiving
      radiotherapy, e.g. the dose to the gonads or to the fetus of a pregnant patient.
      Previously, for external beam radiotherapy a model was developed, which enabled
      this estimation with acceptable accuracy for the range of photon beam energies
      from cobalt-60 to 25 MV, independent of the make of the treatment machines, for
      generally used techniques and for a wide range of distances from the beam axis
      and field sizes [Van der Giessen and Hurkmans, Int. J. Radiat. Oncol. Biol. Phys.
      27, 717-724 (1993); van der Giessen, ibid. 30, 1239-1246 (1994); to appear in
      Int. J. Radiat. Oncol. Biol. Phys.]. In this paper, results of measurements and
      Monte Carlo calculations are reported for evaluation of the dose at large
      distances from some brachytherapy sources. This has resulted in information on
      the behavior of the tissue attenuation factor T(r) for commonly used sources: Co
      60, Ir-192, and Cs-137, in the range of distances up to 60 cm from the source.
      The influence of the size of the phantom was investigated. A mathematical model,
      described earlier by Kornelsen and Young, proved to yield the best fit to the
      results [Br. J. Radiol. 54, 136 (1981)]. Parameters for this model are derived
      for these isotopes. A few experiments in a Rando Alderson phantom are presented
      to support the measurements and the calculations.

PMID- 9157268
TI  - Measurement of the effective attenuation coefficients with model 6711-(125)I
      seeds.

PMID- 9157269
TI  - Using tissue texture surrounding calcification clusters to predict benign vs
      malignant outcomes.
AB  - The positive predictive value of mammography is between 20% and 25% for clustered
      microcalcifications. For very early cancers there is often a lack of concordance
      between mammographic signs and pathology. This study examines the usefulness of
      computer texture analysis to improve the accuracy of malignant diagnosis. Texture
      analysis of the breast tissue surrounding microcalcifications on digitally
      acquired images during stereotactic biopsy is used in this study to predict
      malignant vs benign outcomes. 54 biopsy proven cases (36 benign, 18 malignant)
      are used. The texture analysis calculates statistical features from gray level co
      occurrence matrices and fractal geometry for equal probability and linear
      quantizations of the image data. Discriminant models are generated using linear
      discriminant analysis and logistic discriminant analysis. Results do not differ
      significantly by method of quantization or discriminant analysis. Jackknife
      results misclassify 2 of 18 malignant cases (sensitivity 89%) and 6 of 36 benign
      cases (specificity 83%) for logistic discriminant analysis. From this preliminary
      study, texture analysis appears to show significant discriminatory power between
      benign and malignant tissue, which may be useful in resolving problems of
      discordance between pathological and mammographic findings, and may ultimately
      reduce the number of benign biopsies.

PMID- 9157270
TI  - X-ray imaging with amorphous selenium: optimal spectra for digital mammography.
AB  - The optimum x-ray spectra for acquisition of digital mammographic images using an
      amorphous selenium (a-Se) photoconductor are investigated. The recorded images
      consist of latent charge distributions on the surface of an a-Se plate, which are
      then read out using two methods, laser discharge, or flat panel recharge. The
      investigation is based on a model of the breast previously developed for a
      phosphor-based digital readout system, and has been extended to include the
      effects specific to the use of photoconductors. The effects of plate thickness, x
      ray scatter, readout noise, dose, and the kind of breast tissue on the nature of
      the optimum spectrum are explored for the two readout methods. The results
      indicate that use of a kilovoltage setting in the current mammographic range, and
      a molybdenum target spectrum is appropriate for digital readout of a-Se
      detectors. This conclusion contrasts with the appreciably higher kilovoltages
      traditionally used with the xerographic (toner) readout of latent charge images
      on a-Se.

PMID- 9157271
TI  - Characterization and correction of pulse pile-up in simultaneous emission
      transmission computed tomography.
AB  - We have developed an emission-transmission CT (ETCT) system capable of both
      single-photon emission computed tomography (SPECT) imaging and x-ray transmission
      CT imaging using a common photon counting detector. In principle, SPECT and x-ray
      CT projection data can be acquired simultaneously with the ETCT system; however,
      doing so results in contamination of the SPECT projection data due to pulse pile
      up caused by the relatively high x-ray fluence rate. In this study, we
      characterize the effects of pulse pile-up for simultaneous ETCT imaging through
      computer simulation and experimental studies. We demonstrate that pulse pile-up
      in the SPECT energy window can be well approximated by a simple quadratic
      relationship between the pile-up rate and the x-ray fluence rate for sufficiently
      small x-ray fluence rates. Using this quadratic relationship, we developed a
      simple pile-up correction scheme that subtracts the pile-up counts from the
      emission data and also truncates the exterior regions of the emission projection
      data. Analysis of difference images and profiles indicate that this method
      permits us to reconstruct SPECT images with no apparent noise or resolution
      degradation in comparison to those obtained via sequential emission and
      transmission scans.

PMID- 9157272
TI  - Prevalence of leisure-time physical activity among persons with arthritis and
      other rheumatic conditions--United States, 1990-1991.
AB  - Although regular physical activity is associated with important physical and
      mental health benefits, an estimated 53 million U.S. adults are inactive during
      their leisure time--the period most amenable to efforts to increase physical
      activity. The presence of chronic conditions, especially those associated with
      disabilities, may reduce levels of leisure time physical activity (LTPA).
      Arthritis and other rheumatic conditions (e.g., osteoarthritis, rheumatoid
      arthritis, gout, fibromyalgia, and other diseases of the joints) are leading
      causes of disability and are among the most prevalent chronic conditions in the
      United States, affecting approximately 40 million persons in 1995 and a projected
      60 million persons in 2020. This report uses data from the Health Promotion and
      Disease Prevention (HPDP) supplement of the 1990-1991 National Health Interview
      Survey (NHIS) to provide estimates of LTPA among persons with arthritis and other
      rheumatic conditions by disability status and compares these estimates with those
      for persons without arthritis and other rheumatic conditions. The findings
      indicate that the prevalence of LTPA among persons with arthritis and other
      rheumatic conditions is less than that among persons without arthritis and other
      rheumatic conditions.

PMID- 9157273
TI  - Monthly estimates of leisure-time physical inactivity--United States, 1994.
AB  - Physical inactivity increases the risk for heart disease, diabetes, colon cancer,
      high blood pressure, obesity, osteoporosis, muscle and joint disorders, and
      symptoms of anxiety and depression. However, approximately one third of adults in
      the United States report no leisure-time physical activity, and rates of
      inactivity have been higher in January than in June. Among adults, the prevalence
      of leisure-time physical inactivity is highest among those who are older,
      Hispanic, and residing in southern states. A national health objective for the
      year 2000 is to reduce to < or = 15% the proportion of persons reporting no
      leisure-time physical activity (objecive 1.5). To assist in monitoring efforts to
      achieve this objective, CDC analyzed data from the 1994 Behavioral Risk Factor
      Surveillance system (BRFSS) and estimated for each month the proportion of adults
      from selected demographic groups who reported no leisure-time physical activity.
      The findings indicate seasonal patterns in the prevalence of reported leisure
      time physical inactivity; however, monthly rates of inactivity were higher and
      more stable among older persons, Hispanics, and residents of southern states.

PMID- 9157274
TI  - Human rabies--Kentucky and Montana 1996.
AB  - In October and December 1996, a woman in Kentucky and a man in Montana died from
      rabies. This report summarizes the clinical courses and epidemiologic
      investigation of these cases, which indicate that a bat was the probable source
      of exposure for each case.

PMID- 9157276
TI  - Physician-assisted suicide--the ultimate right?

PMID- 9157275
TI  - Physician-assisted suicide--the ultimate right?

PMID- 9157277
TI  - Physician-assisted suicide--the ultimate right?

PMID- 9157278
TI  - Physician-assisted suicide--the ultimate right?

PMID- 9157279
TI  - Physician-assisted suicide--the ultimate right?

PMID- 9157280
TI  - Physician-assisted suicide--the ultimate right?

PMID- 9157281
TI  - Physician-assisted suicide--the ultimate right?

PMID- 9157283
TI  - Turner's syndrome.

PMID- 9157282
TI  - Physician-assisted suicide--the ultimate right?

PMID- 9157284
TI  - Turner's syndrome.

PMID- 9157285
TI  - Turner's syndrome.

PMID- 9157286
TI  - Management of venous thromboembolism.

PMID- 9157287
TI  - Management of venous thromboembolism.

PMID- 9157288
TI  - Management of venous thromboembolism.

PMID- 9157289
TI  - A pitfall in assessing gastric lymphoma after eradication of Helicobacter pylori.

PMID- 9157290
TI  - Treatment of chronic cervical zygapophyseal-joint pain.

PMID- 9157291
TI  - Hemochromatosis.

PMID- 9157292
TI  - Impact of combination therapy for HIV infection on inpatient census.

PMID- 9157293
TI  - [Nutritional physiology of whey and whey components].
AB  - Deriving from positive effects of whey drinking cures in antiquity, the Middle
      Ages and modern time, a review is given on nutritional significance of whey. The
      proteins are essential components of whey and belong to the proteins with highest
      biological value because of their amino acid composition. Besides, they show
      fundamental functional properties, which enable a varied application in foods,
      dietetic foods and beverages in form of different whey products (powder, protein
      concentrates and isolates). Whey proteins have found considerable usage in
      infant's nutrition as whey predominant formulas as well as whey protein
      hydrolysates in case of cow's milk protein intolerances. A recent field of
      research are biological active peptide sequences which become effective during
      digestion and are of importance for secretion of entero hormones as well as for
      immune enhancing effects. They may contribute to assess the biological value of
      whey proteins under enlarged points of view and to develop new application forms
      and areas. It is pointed to further fields of application (e.g. adipositas, gout,
      kidney insufficiency). Concerning the quantitatively most dominant lactose in
      whey, it is dealt with its importance for the healthy development of infants
      (adaptation to the increased lactose content of mother's milk) as well as with
      lactose intolerance and galactosaemia. In case of mineral salts of whey it is
      emphasized the high nutrient density of calcium (prophylaxis for osteoporosis),
      the beneficial Ca:P and Na:K proportions (antihypertensive in case of the last
      one), the promotion of absorption of mineral salts by lactose, and the high
      content of iodine. The whey is rich in B-vitamins, which contribute essentially
      for their satisfaction or requirement in case of a corresponding consumption. To
      be emphasized is the vitamin B12 in milk and whey, which is the sole source of
      this indispensable nutrient for blood-formation and cell division in lacto-ovo
      vegetarian nutrition. In conclusion, a summarizing dietetics valuation of whey is
      performed.

PMID- 9157294
TI  - [Several patients with memory disorders].
AB  - In three patients, referred to a memory clinic because of memory impairment,
      three different types of memory dysfunction were observed: a deficit in encoding
      of new episodic memories, a relatively pure loss of semantic memory and an
      impairment in retrieval of stored information. These patients were diagnosed as
      suffering from Alzheimer's disease, semantic dementia and frontotemporal dementia
      respectively. The diagnosis was essential in determining the individual
      management strategy.

PMID- 9157295
TI  - [Vascularization and perfusion of tumors as target in cancer therapy].
AB  - Many tumours depend on the formation of an own vascular system to support
      progressive tumour growth. This is accomplished through induction of vessel
      growth from pre-existing vessels, a process called neo-angiogenesis. Therefore,
      inhibiting neo-angiogenesis and modulating tumour perfusion constitute attractive
      possibilities for tumour therapy, combined, of course, with treatment aimed at
      the tumour cells themselves. By now many angiogenesis inhibitors have been
      developed, but their use is mostly still experimental. They inhibit endothelial
      proliferation and migration (fumagillin derivates, angiostatin, suramin) or
      prevent proteolytic degeneration of the extracellular matrix by products of the
      tumour (metalloproteinase inhibitors). Improving tumour oxygenation and perfusion
      by carbogen inhalation and nicotinamide or vasoactive agents (flunarizine,
      verapamil, nicotinamide) enhances the effects of radiotherapy and improves
      delivery of chemotherapeutic agents to the tumour. Research is currently in
      progress into the efficacy of accelerated radiotherapy in combination with
      carbogen inhalation and administration of nicotinamide in tumours of the head and
      neck, bladder, bronchi and brain.

PMID- 9157296
TI  - [Postmenopausal hormone replacement therapy and cancer of the female genitalia
      and breast].
AB  - Oestrogen replacement therapy (ORT) significantly increases the relative risk
      (RR) of endometrial cancer, especially long-term oestrogen use (RR: 9.5; 95%
      confidence interval (CI): 7.4-12.3). Addition of a progestin to ORT reduces this
      increased risk completely or largely. The risk of breast cancer is increased
      after ORT of 5 years or longer (RR: 1.23; 95% CI: 1.08-1.40). Addition of a
      progestin does not reduce this increased risk. The possibility cannot be excluded
      that long-term ORT increases the risk of epithelial ovarian cancer. No
      significant association between ORT and cervical cancer has been demonstrated. It
      is safe to prescribe ORT for a period shorter than 5 years for women with
      menopausal symptoms. Addition of a progestin is indicated when the uterus is in
      situ. Hormonal supplementation therapy is to be discouraged in women treated for
      breast cancer, may be considered in young women previously treated for
      endometrial or ovarian cancer with a good prognosis and severe menopausal
      symptoms and is justified in women previously treated for cervical cancer.

PMID- 9157297
TI  - [Urinary tract infections in patients with diabetes mellitus].
AB  - The urinary tract is the principal site of infection in diabetics. A changed
      bacterial adhesion to the uroepithelium, partly as a result of a changed and
      lowered Tamm Horsfall Protein, and granulocyte dysfunction, possibly as a result
      of an abnormal intracellular calcium metabolism, are involved in the pathogenesis
      of urinary tract infections in diabetics. The main risk factors for bacteriuria
      in female diabetics are more advanced age and more frequent sexual intercourse.
      Diabetic patients run an increased risk of complications of urinary tract
      infection. If a symptomatic infection exists, the treatment of choice is
      antibiotics which can reach high tissue levels. It is not clear if asymptomatic
      bacteriuria needs medical treatment.

PMID- 9157298
TI  - [Favorable results of plasmapheresis in severe myasthenia gravis].
AB  - OBJECTIVE: Evaluation of the additional effect of plasma exchange in treatment
      with steroids of severe myasthenia gravis. DESIGN: Retrospective study. SETTING:
      Department of Neurology, University Hospital of Groningen, the Netherlands.
      PATIENTS AND METHODS: The clinical course was analysed in 24 patients with a
      total of 28 plasma exchange treatments. Prednisone was introduced or its
      maintenance dose was increased in 19 cases. Another 13 patients with severe
      myasthenia gravis were included to study the effect of prednisone monotherapy.
      RESULTS: Of the patients treated with plasma exchange and steroids 71% improved
      within the first week of treatment as against only 15% of the patients treated
      with prednisone monotherapy. After two weeks of plasma exchange plus prednisone
      or prednisone monotherapy, 88% and 69%, respectively were ameliorated. None of
      the patients receiving plasma exchange deteriorated or experienced adverse
      effects or complications due to plasma exchange. Of the patients receiving
      prednisone monotherapy 31% deteriorated in the first week of treatment.
      CONCLUSION: Patients with severe myasthenia gravis may safely be treated with
      plasma exchange in combination with prednisone. In our patient group, a state of
      rapid aggravation was cut short more quickly by prednisone plus plasma exchange
      than by prednisone monotherapy.

PMID- 9157299
TI  - [2 patients with atypical manifestations of cat-scratch disease].
AB  - In 2 boys aged 8 years and 10 months, respectively, uncommon manifestations of
      cat scratch disease were seen. The first patient had acute encephalopathy: coma
      and generalized tonic-clinic convulsions. The second patient was presented with
      fever and peripheral lymphadenopathy in combination with hypodense lesions in the
      liver on ultrasound. Diagnosis was established on the clinical picture and the
      positive results of serological testing of antibody titres for Bartonella
      henselae. Both patients recovered completely within 2 months.

PMID- 9157300
TI  - [Visceral granulomas and pericardial effusion caused by a Bartonella henselae
      infection].
AB  - A 57 year-old woman was seen after a three-week period of upper abdominal pain,
      nausea, fever, headache and exertional dyspnoea. Laboratory examination showed an
      elevated ESR and serum gamma-GT activity. The chest X-ray showed cardiomegaly
      resulting from a pericardial effusion as was demonstrated by echocardiography. An
      abdominal CT-scan disclosed multiple hypodense lesions in the liver and spleen
      and lymphadenopathy along the hepatoduodenal ligament. Liver biopsy showed a
      necrotising granulomatous hepatitis. A recent infection with Bartonella,
      presumably B. henselae, was demonstrated serologically. The patient was treated
      with clarithromycin and recovered.

PMID- 9157301
TI  - [Reversible dementia due to valproic acid therapy].
AB  - A progressive dementia syndrome (DSM IV) with frontal-subcortical features
      developed in a 72-year-old woman during valproate therapy (Depakine).
      Discontinuation of valproate resulted in complete recovery. Drugs are a common
      cause of reversible dementia. The association of dementia with valproate therapy
      is rare. Features of a subcortical dementia are indicative of a reversible cause.
      In addition, the possible role of drugs should always be considered in patients
      with cognitive decline.

PMID- 9157303
TI  - [Little benefit of medical-specialist follow-up for detecting recurrencies after
      treatment for endometrial or cervix carcinoma].

PMID- 9157302
TI  - [Gluten as food additive in The Netherlands: cheese forbidden for celiac
      patients?].
AB  - A new coating for cheese, to be introduced in May, consists entirely of natural
      degradable components. The coating is based on wheat gluten. This increase in the
      amount of gluten in the Dutch diet may lead to overt coeliac disease in people
      with a subclinical form of it, and will limit the dietary choices of patients
      already suffering from the disease.

PMID- 9157304
TI  - [Medical disciplinary jurisprudence in The Netherlands; a 10-year survey].

PMID- 9157306
TI  - [Surgery in the last 40 years; looking back in wonder].

PMID- 9157305
TI  - [Bisphosphonates in osteoporosis; a reevaluation].

PMID- 9157307
TI  - [Surgery in the last 40 years; looking back in wonder].

PMID- 9157308
TI  - [Neurodegenerative disorders and the role of trinucleotide repeat expansion].

PMID- 9157309
TI  - [Antibiotics in otitis media with effusion].

PMID- 9157310
TI  - The overrepresentation of the fovea and adjacent retina in the striate cortex and
      dorsal lateral geniculate nucleus of the macaque monkey.
AB  - The central part of the retina, which includes the fovea, is substantially
      overrepresented in the topographic map of the retina in the striate cortex. We
      tested whether this simply reflects the uneven distribution of ganglion cells in
      the retina in accordance with the "principle" of peripheral scaling, or whether
      there is additional expansion of the fovea and adjacent retina in the
      retinocortical projection. Wheatgerm agglutinated horseradish peroxidase was
      injected into the striate cortex of three rhesus macaque monkeys so as to
      surround the representation of the fovea at a mean eccentricity of 8.6 degrees,
      and the retinae were processed histochemically to stain the retrogradely and
      transneuronally labelled ganglion cells which projected topographically to the
      injection sites. This enabled regions of the striate cortex to be related
      precisely to corresponding regions of the dorsal lateral geniculate nucleus and
      retina. Mathematical models of the distribution of ganglion cells in the retina,
      clipped, three-dimensional computer reconstructions of the striate cortex and
      lateral geniculate nucleus, and counts of neurons in the latter, were used to
      calculate the proportion of neurons allocated to the marked perifoveal region at
      each stage of projection. This was used to calculate the relative allocation of
      neurons to the representation of the fovea and surrounding retina among the
      different stages of the visual pathway. The values obtained showed that the
      cortical representation of the perifovea was expanded two to three times more
      than could be accounted for on the basis of ganglion cell topography in the
      retina, and that the expansion occurred both between the retina and the thalamus,
      and between the thalamus and the cortex. These results are inconsistent with the
      idea that peripheral scaling is a general principle of sensory representation in
      the cortex. They could also explain why many visual thresholds, including
      hyperacuities, cannot be accounted for by peripheral factors such as ganglion
      cell density.

PMID- 9157311
TI  - Dopaminergic neuronal degeneration and motor impairments following axon terminal
      lesion by instrastriatal 6-hydroxydopamine in the rat.
AB  - 6-Hydroxydopamine-induced nerve terminal lesion of the nigrostriatal system may
      provide a partial lesion model of Parkinson's disease useful for the assessment
      of neuroprotective treatments and behavioral recovery after therapeutic
      intervention. The aim of the present study was to assess the retrograde
      degenerative changes in the dopaminergic neurons of the substantia nigra and the
      associated behavioral and neurochemical consequences of intrastriatal injections
      of 6-hydroxydopamine in young adult rats. Four groups of rats were
      stereotaxically injected in the right striatum with graded doses of 6
      hydroxydopamine ranging from 0 to 20 mu g. Structural and functional deficits
      were quantified by tyrosine hydroxylase-immunoreactive nigral cell numbers,
      striatal dopamine content, skilled paw use, and drug-induced rotation. The
      results show that striatal 6-hydroxydopamine lesions produce dose-dependent
      decreases in striatal dopamine levels and tyrosine hydroxylase-immunoreactive
      cell numbers in the ipsilateral substantia nigra, accompanied by a significant
      long-lasting atrophy of the remaining dopaminergic neurons. Paw reaching test
      scores on the side contralateral to the lesion were non-linearly correlated with
      dopaminergic neuronal cell loss and exhibited a clear symptomatic threshold such
      that impaired paw use appeared only after >50% loss of nigral dopamine neurons or
      a reduction of 60-80% of striatal dopamine levels. The behavioral, cellular, and
      neurochemical effects of the nerve terminal lesion thus bear some resemblance to
      the early stages of Parkinson's disease, where the severity of motor impairment
      is correlated with the loss of dopamine in the striatum and dopaminergic neuronal
      loss in the substantia nigra. Rats with intrastriatal 6-hydroxydopamine lesions
      thus provide a model of progressive dopamine neuron degeneration useful not only
      for the exploration of neuroprotective therapeutic intervention but also for the
      study of mechanisms of functional and structural recovery after subtotal damage
      of the nigrostriatal dopamine system.

PMID- 9157313
TI  - Differential effects of histamine on the N-methyl-D-aspartate channel in
      hippocampal slices and cultures.
AB  - The effect of histamine on N-methyl-D-aspartate currents was investigated in
      pyramidal neurons in the CA1 region of acute hippocampal slices from juvenile
      rats. The objective was to compare histamine effects in the slice with those
      previously reported in acutely dissociated and cultured hippocampal neurons.
      Micromolar concentrations of histamine had no effect on N-methyl-D-aspartate
      mediated excitatory postsynaptic currents in the slice, in contrast to the large
      enhancement seen in culture under identical conditions. However, millimolar
      concentrations of histamine blocked these currents both in the slice and in
      culture. Possible reasons for the lack of enhancement in the slice were explored
      as follows. (1) Histamine could not penetrate the slice or was already present at
      high concentrations inside the slice. This was tested by recording N-methyl-D
      aspartate currents elicited in outside-out patches pulled from the somas of CA1
      slice neurons. Histamine still had no effect in patches, whereas the
      corresponding experiment for cultured neurons showed robust enhancement. (2)
      Slices release an endogenous ligand that binds with high affinity to the
      histamine site on the N-methyl-D-aspartate receptor, blocking its activation.
      This was tested by superfusing cultures with supernatant from homogenized slice
      tissue. Histamine enhancement was maintained in these cultures. (3) CA1 slices
      and cultures express different N-methyl-D-aspartate receptor subtypes. The
      reverse transcription-polymerase chain reaction technique was used to examine the
      expression of messenger RNA encoding N-methyl-D-aspartate receptor subunits in
      the two systems. No difference was found in the whole-tissue expression of
      messenger RNA for the NR2A, 2B or 2C subunits or for the eight known splice
      variants of the NR1 subunit. It is hypothesized that the differential enhancing
      effect of histamine in slices and culture involves posttranslational
      modifications or other factors that modulate the N-methyl-D-aspartate
      receptor/ion channel according to its environment.

PMID- 9157312
TI  - Conditions required for polysynaptic excitation of dentate granule cells by area
      CA3 pyramidal cells in rat hippocampal slices.
AB  - Under control conditions, stimulation of area CA3 pyramidal cells in slices can
      produce inhibitory postsynaptic potentials in granule cells by a polysynaptic
      pathway that is likely to involve hilar neurons [Muller W. and Misgeld U. (1990)
      J. Neurophysiol. 64, 46-56; Muller W. and Misgeld U. (1991) J. Neurophysiol. 65,
      141-147; Scharfman H. E. (1993) Neurosci. Lett. 156, 61-66; Scharfman H. F.
      (1994) Neurosci. Lett. 168, 29-33]. When slices are disinhibited, excitatory
      postsynaptic potentials occur after the same stimulus [Sharfman H. E. (1994) J.
      Neurosci. 14, 6041-6057]. The excitatory postsynaptic potentials are likely to be
      mediated by pyramidal cells that innervate hilar mossy cells, which in turn
      innervate granule cells. [Scharfman H. F. (1994) J. Neurosci 14, 6041-6057].
      These pathways are potentially important, because they could provide positive or
      negative feedback from area CA3 to the dentate gyrus. However, it is not clear
      when the CA3-mossy cell-granule cell excitatory pathway operates, because to date
      it has only been described in detail when GABA(A) receptors are blocked
      throughout the entire slice [Scharfman H. E. (1994) J. Neurosci 14, 6041-6057].
      Furthermore, the monosynaptic excitatory synaptic connections between these cells
      have only been observed in the presence of bicuculline [Scharfman H. F. (1994) J.
      Neurophysiol. 72, 2167-2180; Scharfman H. E. (1995) J. Neurophysiol. 74, 179
      194]. Yet in vivo data suggest that a CA3-mossy cell-granule cell excitatory
      pathway may be active under some physiological conditions, because granule cells
      discharge in association with sharp wave population bursts of CA3 [Ylinen A., et
      al. (1995) Hippocampus 5, 78-90]. To address whether the CA3-mossy cell-granule
      cell pathway occurs without global disinhibition of the slice, and where in the
      network disinhibition may be required, the effects of area CA3 stimulation on
      granule cells was examined after focal application of the GABAA receptor
      antagonist bicuculline to restricted areas of hippocampal slices. A micropipette
      containing 1 mM bicuculline was placed transiently either (i) in the area CA3
      cell layer, (ii) the granule cell layer, (iii) the hilus, or (iv) more than one
      site in succession. If a small segment of the CA3 pyramidal cell layer or the
      hilus was disinhibited, or bicuculline was applied to both regions, area CA3
      stimulation still evoked inhibitory postsynaptic potentials in granule cells. In
      fact, inhibitory postsynaptic potentials were enhanced under these conditions,
      probably because excitation of inhibitory cells was increased. When bicuculline
      was applied just to the area near an impaled granule cell, all inhibitory
      postsynaptic potentials evoked in that cell were blocked, but no underlying
      excitatory postsynaptic potential was uncovered. If bicuculline was applied
      focally to either area CA3 or the hilus and the impaled granule cell, CA3
      stimulation subsequently evoked excitatory postsynaptic potentials in that
      granule cell, presumably because excitatory neurons innervating granule cells
      were disinhibited while the effects of inhibitory cells on granule cells were
      blocked. Excitatory postsynaptic potentials were produced without bicuculline
      application in three of seven cells, simply by stimulating the fimbria
      repetitively. Thus, if bicuculline is applied to different sites in the slice,
      different effects occur on the inhibitory postsynaptic potentials of granule
      cells that are evoked by a fimbria stimulus. If bicuculline is applied to both
      the granule cell soma and either area CA3 or the hilus, inhibitory postsynaptic
      potentials are reduced, and reveal that excitatory postsynaptic potentials can be
      produced by the same stimulus. (ABSTRACT TRUNCATED)

PMID- 9157314
TI  - Striatal and cortical projections of single neurons from the central lateral
      thalamic nucleus in the rat.
AB  - Striatal and cortical projections arising from the central lateral thalamic
      nucleus were studied in rats by tracing the axons of small pools of neurons
      labeled anterogradely with biocytin. Cells of the central lateral nucleus have a
      morphology that conforms to the classic descriptions of the bushy cells which
      represent the main neuronal type of most thalamic nuclei. They display many short
      radiating dendrites studded with sessile spines, protrusions and grapelike
      appendages. The total extent of their dendritic fields is about 250 mu m. After
      leaving the nucleus, all central lateral axons course through the rostrolateral
      pole of the thalamic reticular nucleus, where they branch profusely, enter the
      striatum, where they distribute collaterals, and arborize in the motor cortex. At
      striatal level, central lateral fibers form a loosely organized network composed
      of varicose axonal branches that appear to contact en passant several striatal
      neurons. In the cortex. central lateral axons from multiple (four to five patches
      of terminations in layers Va and III aligned along the rostrocaudal extent of the
      motor area. The projection to layers I and II is very sparse, consisting of
      occasional branches which show few ramifications. Our results indicate that most,
      and perhaps all, central lateral relay neurons project to both the striatum and
      cerebral cortex. The patchy innervation of mid cortical layers of the frontal
      motor areas by central lateral afferents strongly argues against the nonspecific
      character of this projection. It is proposed that the central lateral nucleus,
      which receives a strong innervation from brainstem cholinergic afferents, takes
      part in a mechanism of attention related to the central initiation of directed
      patterns of movements.

PMID- 9157316
TI  - Loss of vasopressin-immunoreactive neurons in alcoholics is dose-related and time
      dependent.
AB  - The chronic consumption of alcohol significantly reduces the number of
      vasopressin-producing neurons in the rat supraoptic nucleus [Maderia et al.
      (1993) Neourscience 56, 657-672] suggesting this region is particularly
      vulnerable to alcohol neurotoxicity. As hypothalamic vasopressin producing
      neurons are necessary for fluid homeostasis, it is important to assess if similar
      changes occur in humans. We analysed arginine vasopressin-immunoreactive neurons
      in the magnocellular hypothalamic nuclei of ten chronic alcoholic men (consuming
      > 80 g of ethanol per day) and four age- and sex-matched controls (consuming <
      10g of ethanol per day). Brains were collected at autopsy and fixed in formalin.
      Serial 50 mu m-thick-sections of the hypothalamus were stained and assessed. The
      volume of the paraventricular and supraoptic nuclei and number of neurons were
      estimated using Cavalieri's principle and the optical dissector technique. The
      volume of these nuclei significantly correlated with the number of neurons and
      the number of vasopressin-immunoreactive neurons, and these measures
      significantly correlated with the maximum daily intake of alcohol. There was a
      loss of neurons at consumption levels greater than 100 g of ethanol per day,
      principally affecting the supraoptic nucleus although neuron loss also occurred
      in the paraventricular nucleus in cases with long histories of alcohol
      consumption. These results indicate that chronic alcohol consumption is toxic to
      hypothalamic vasopressin-producing neurons in a concentration- and time-dependent
      manner. As these magnocellular neurons are osmo-receptive, neuronal loss may
      result in fluid imbalances.

PMID- 9157315
TI  - Tonic activation of presynaptic GABA(B) receptors on thalamic sensory afferents.
AB  - The presence and role of presynaptic GABA(B) receptors in the control of
      excitatory amino acid-medicated transmission were investigated (using sharp
      electrode recordings) in the rat dorsal lateral geniculate nucleus and
      ventrobasal thalamus in vitro by comparing the effects of the selective GABA(B)
      receptor agonist, (+ or -)-baclofen, and of two antagonists, CGP 35348 and 2
      hydroxy-saclofen, on the excitatory postsynaptic potentials evoked in
      thalamocortical neurons by stimulation of the sensory afferents. Application of
      CGP 35348 alone blocked the GABA(B) receptor-mediated inhibitory postsynaptic
      potential evoked in the dorsal lateral geniculate nucleus by stimulation of the
      optic tract (n = 5), but had no effect on the resting membrane potential and
      input resistance of thalamocortical cells (n = 6). In contrast, 2-hydroxy
      saclofen caused a hyperpolarization (6.9 + or - 0.5 mV, n = 10) and a decrease in
      the apparent input resistance (26.3 + or - 2.6%, n = 10). This effect of 2
      hydroxy-saclofen was antagonized by CGP 35348. When bicuculline was present in
      the perfusion medium and following intracellular injection of QX 314, GABA(A) and
      GABA(B) receptors in the recorded neurons were blocked. Under this condition,
      application of baclofen decreased the amplitude of the medial lemniscus- and
      optic tract-evoked excitatory postsynaptic potentials in the two thalamic nuclei
      investigated. This effect was fully antagonized by CGP 35348 and only partially
      by 2-hydroxy-saclofen. CGP 35348 alone increased (19.3 + or - 4.3%, n = 5) and 2
      hydroxy-saclofen alone decreased (29.9 + or - 8.6%, n = 5) the amplitude of the
      excitatory postsynaptic potential. This effect of 2-hydroxy-saclofen was not
      blocked by CGP 35348. These results indicate that presynaptic GABA(B) receptors
      are present on the terminals of the sensory afferents in the rat dorsal lateral
      geniculate nucleus and in the ventrobasal thalamus. These receptors are tonically
      activated by endogenous GABA, at least in vitro, and provide a negative control
      mechanism by which the excitatory amino acid-mediated transmission within these
      nuclei can be regulated. In contrast, the endogenous GABA level is not sufficient
      for a tonic activation of postsynaptic GABA(B) receptors. Furthermore, these
      results indicate that 2-hydroxy-saclofen acts as a partial agonist on
      postsynaptic CGP 35348-sensitive GABA(B) receptors, and that, in addition to its
      antagonist action on presynaptic CGP 35348-sensitive GABA(B) receptors, it also
      has an effect on either presynaptic, CGP 35348-insensitive GABA(B) receptors
      and/or another presynaptic receptor type.

PMID- 9157317
TI  - The structural localization of galanin, and its function in modulating
      acetylcholine release in the olfactory bulb of adult rat.
AB  - The localization of galanin immunoreactivity was analyzed within the olfactory
      bulb of adult rats. Galanin-positive neurons were differentially distributed
      among the bulb layers. The density of stained neurons was highest in the
      glomerular and external plexiform layers. According to morphology, size, location
      and arrangement, a large proportion of galanin-immunoreactive neurons corresponds
      to external tufted cells and short-axon neurons in the superficial part of the
      external plexiform and glomerular layers. A smaller number were middle tufted
      cells and short-axons neurons while only a few short-axon neurons were labeled in
      the granule cell layer. Galanin-stained nerve fibers had different structures
      (thick fibers with or without varicosities, and thin fibers with or without
      varicosities). Among them were afferent immunoreactive nerve fibers entering the
      bulb through the olfactory nerve layer, but penetrating superficial layers.
      Correspondingly, a large number of galanin-positive axons (with or without
      varicosities) were observed in the olfactory nerve layer. A number of galanin
      positive nerve fibers was also present in the glomerular and internal plexiform
      layers, while these fibers were scarce in the granule cell layer, their density
      was lowest in the external plexiform layer. These results suggest that galanin
      positive axons present in the olfactory bulb originate from at least four
      different sources. From the periphery axon bundles enter the bulb together with
      olfactory nerve fibers from the rostral direction and with a fiber bundle from
      the ventral posterior surface, i.e. at the border between the olfactory tract and
      the main olfactory bulb along a large blood vessel. Central sources are local
      interneurons in the olfactory bulb and some extrabulbar brain regions. Double
      labeling experiments combining acetylcholinesterase histochemistry with galanin
      immunocytochemistry did not show any co-localization of acetylcholinesterase and
      galanin in nerve cell perikarya or nerve fibers. Synthetic porcine galanin (1-29)
      promoted acetylcholine release in olfactory bulb tissue slices, suggesting that
      galanin can effectively modulate cholinergic transmission and perhaps other forms
      of neuronal transmission. It is concluded that galanin may be significantly
      involved in olfactory processing at cellular and synaptic levels.

PMID- 9157318
TI  - Different rates of horseradish peroxidase transport in the optic nerve of
      neonatal and adult rats.
AB  - In order to evaluate the effects of age upon fast transport kinetics, we studied
      the velocity of horseradish peroxidase transport along the optic pathway of
      neonatal and adult rats. Rate of horseradish peroxidase movement was assessed by
      following the displacement of horseradish peroxidase activity in the optic nerve
      with time after injection. We estimated a rate about 100 mm/day for bidirectional
      transport of horseradish peroxidase in the optic nerve of neonatal rats, while a
      two-fold higher rate was observed for anterograde transport in adult animals.
      Developmental regulation of fast transport rate may ensure relative constancy of
      the time required to connect the cell body with axon terminals.

PMID- 9157319
TI  - Neurotoxic and neurotrophic effects of chronic N-methyl-D-aspartate exposure upon
      mesencephalic dopaminergic neurons in organotypic culture.
AB  - Current theories regarding the mechanisms of degeneration of dopaminergic
      nigrostriatal neurons in Parkinson's disease suggest a pivotal role for
      excitotoxicity. In this study, the effects of chronic exposure of rat ventral
      mesencephalic slice cultures to the excititoxin N-methyl-D-aspartate, were
      investigated. Chronic (18 day) exposure to N-methyl-D-aspartate produced widely
      varying, dose-dependent effects. High doses (100 mu M) caused a pronounced
      toxicity upon tyrosine hydroxylase-positive neurons, with the surviving neurons
      possessing shrunken somata and stunted neurites: co-administration of the N
      methyl-D-aspartate receptor antagonist MK-801, inhibited N-methyl-D-aspartate
      induced toxicity. In contrast, exposure to a low concentration of N-methyl-D
      aspartate (0.1 mu M), stimulated the outgrowth of tyrosine hydroxydase-positive
      neurites from the culture; this effect was abolished by MK-801. Chronic
      application of glutamate had similar, though not as pronounced, growth-promoting
      actions. However, the concentration of glutamate required was 1000 times that of
      N-methyl-D-aspartate, due to the presence ot high-affinity glutamate transport
      mechanisms. Cultures exposed to a submicromolar concentration of N-methyl-D
      aspartate exhibited a significant resistance to subsequent exposure to a lethal
      (300 mu M) concentration of the toxin. It would thus appear that N-methyl-D
      aspartate may have both trophic and toxic actions upon dopaminergic neurons in
      culture. Moreover, the ability of low doses of N-methyl-D-aspartate to protect
      neurons in this critical brain region may be of relevance to future attempts to
      arrest the degeneration associated with Parkinson's disease. The putative
      mechanisms of these phenomena are discussed.

PMID- 9157320
TI  - Neuronal and glial handling of glutamate and glutamine during hypoosmotic stress:
      a biochemical and quantitative immunocytochemical analysis using the rat
      cerebellum as a model.
AB  - Biochemical and immunocytochemical analyses were performed to resolve how
      glutamate and glutamine are handled in rat cerebellar cortex in acute hypoosmotic
      stress. Rats were subjected to a 15-20% reduction in plasma osmolality by
      intraperitoneal injection of distilled water and then perfusion fixed after 4 or
      8 h survival. Some rats in the latter group had their plasma isoosmolality
      restored by injections of hypertonic saline 4 h prior to perfusion. Water loading
      caused a pronounced increase in the tissue level of glutamine and an equimolar
      decrease in the level of glutamate after 4 h survival. The increase in glutamine
      was transient, as judged by analyses at 8 h survival. Light microscopic
      immunocytochemistry revealed a pronounced enhancement of the glutamine
      immunolabelling of glial cells (Golgi epithelial cells and astrocytes), including
      their perivascular end feet, and quantitative immunogold analyses at the electron
      microscopic level showed that this enhancement reflected a 50% increase in the
      intracellular concentration of fixed glutamine. Since water loading was
      associated with glial swelling this change corresponded to a several-fold
      increase in the glial content of glutamine. There was a modest reduction in the
      overall staining intensity for glutamate. The biochemical and immunocytochemical
      changes were reversed upon restoration of plasma osmolality by hypertonic saline.
      These findings suggest that hypoosmotic stress causes an increased conversion of
      glutamate to glutamine in glial cells and that the latter amino acid is
      subsequently lost from the tissue. The flux of glutamate carbon skeletons through
      the glutamine synthetase pathway in glia, prior to an efflux to the systemic
      circulation, may explain how glutamate, and excitatory transmitter and potential
      toxin, can be used as an organic osmolyte in brain tissue.

PMID- 9157321
TI  - Unit activity of rat basal forebrain neurons: relationship to cortical activity.
AB  - Unit activity in the magnocellular basal forebrain nucleus was examined to
      characterize discharge patterns during synchronized and desynchronized
      electroencephalogram. Two types of basal forebrain neurons were identified by
      their firing pattern under urethane anaesthesia: bursting and tonic neurons.
      Bursting neurons (62.9%) were characterized by a spontaneous firing that
      consisted of periodic bursts of two to six spikes that occurred at 0.3 to 2 Hz
      and were phase-locked with the electroencephalogram slow waves. Tonic neurons
      (37.1%) displayed spontaneous single spike firing at 12.1 + or - 1.6Hz. The
      firing of most of them was not related to the slow waves. Both neuronal types
      changed their firing patterns during the electroencephalogram desynchronization
      elicited by either electrical stimulation of the pedunculopontine tegmentum or
      pinching the rat's tail. Bursting neurons changed from the bursting mode to a
      tonic mode of discharge pattern, increasing their firing rate, while tonic cells
      were inhibited during electroencephalogram desynchronization. Multiunit
      recordings revealed that bursting cells discharged synchronously during periods
      of electroencephalogram slow waves, but that synchronization disappeared during
      electroencephalogram desynchronization. No correlation was found between the
      spike discharges of different tonic cells nor between bursting and tonic cells.
      However, bursting neurons, but not tonic neurons, were correlated with the spike
      firings of neocortical neurons during electroencephalogram slow waves. The
      rhythmic activity of neither neocortical nor bursting basal forebrain cells was
      found under pentobarbital anaesthesia. The characteristics of the discharge
      pattern shown by bursting basal forebrain neurons suggest that this type of cell
      could be cholinergic. Thus, bursting basal forebrain neurons may release
      acetylcholine in the cortex rhythmically, enhancing the rhythmic activity of
      cortical neurons during slow-wave sleep. It is concluded that basal forebrain
      neurons may contribute to the generation of the electroencephalogram slow waves.

PMID- 9157322
TI  - Differential messenger RNA expression of prodynorphin and proenkephalin in the
      human brain.
AB  - The opiate system is involved in a wide variety of neural functions including
      pain perception, neuroendocrine regulation, memory, drug reward, and tolerance.
      Such functions imply that endogenous opioid peptides should have anatomical
      interactions with limbic brain structures believed to be involved in the
      experience and expression of emotion. Using in situ hybridization histochemistry,
      the messenger RNA expression of the opioid precursors, prodynorphin and
      proenkephalin, was studied in whole hemisphere human brain tissue. Different
      components of the limbic system were found to be characterized by a high gene
      expression of either prodynorphin or proenkephalin messenger RNA. Brain regions
      traditionally included within the limbic system (e.g. amygdala, hippocampus,
      entorhinal cortex and cingulate cortex) as well as limbic-associated regions
      including the ventromedial prefrontal cortex and patch compartment of the
      neostriatum showed high prodynorphin messenger RNA expression. In contrast, high
      levels of proenkephalin messenger RNA were more widely expressed in the
      hypothalamus, periaqueductal gray, various mesencephalic nuclei, bed nucleus of
      the stria terminalis, and ventral pallidum; brain regions associated with
      endocrine-reticular-motor continuum of the limbic system. The marked anatomical
      dissociation between the expression of these two opioid peptide genes, seen
      clearly in whole hemisphere sections, indicates that distinct functions must be
      subserved by the prodynorphin and proenkephalin systems in the human brain.

PMID- 9157323
TI  - Hypoxia decreases opioid delta receptor expression in mouse brain.
AB  - Delta opioid receptor activation is protective during hypoxic injury. Many
      adaptive responses occur during exposure to hypoxia to facilitate survival. It is
      possible that increased activity of the delta opioid receptor system is one such
      adaptation. We tested the hypothesis that mice exposed to prolonged hypoxia have
      increased expression of the delta opioid receptor in brain tissue. Prolonged
      exposure to hypoxia (9% oxygen, balance nitrogen) continuously for seven days
      selectively decreased delta opioid receptor expression in mouse brain homogenate.
      The same hypoxic treatment had no effects on either mu or kappa opioid receptor
      expression, indicating that this response was not due to non-selective
      degradation of protein. Shorter term hypoxic treatments (one day and three days)
      did not induce changes in delta opioid receptor expression in whole brain
      homogenate. Binding assays were also conducted in grossly dissected brain regions
      (cortex, midbrain, hindbrain) to determine whether the shorter term treatments
      would induce changes in receptor expression in more discrete areas. No consistent
      changes in delta opioid receptor expression were detected in these brain regions.
      These data demonstrate that opioid delta receptors are hypoxia sensitive and may
      be a part of an adaptive process to increase survival in the organism. One
      possible cause for the decrease in delta opioid receptor expression following
      seven days of hypoxic exposure may be receptor down-regulation caused by an
      increased release of endogenous substances acting at delta receptors. As delta
      opioid receptor agonists appear promising for therapeutic potential in management
      of hypoxic injury, changes in delta receptor expression in response to long-term
      hypoxia could impact potential utilization of delta agonists in patients
      suffering chronic hypoxia.

PMID- 9157324
TI  - Chronic corticosterone treatment elicits dose-dependent changes in mouse brain
      alpha-bungarotoxin binding.
AB  - Previous studies have shown that adrenalectomy results in a small increase in
      hippocampal alpha-bungarotoxin binding, whereas seven days of chronic treatment
      with high doses of corticosterone results in decreases in alpha-bungarotoxin
      binding in several brain regions. The studies reported here examined the effects
      of different doses of corticosterone on brain alpha-bungarotoxin binding. C3H
      mice were adrenalectomized and treated with corticosterone-containing pellets
      (0.5-60%) for four days. Alpha-Bungarotoxin binding was measured in eight brain
      regions. Chronic treatment with corticosterone resulted in plasma corticosterone
      levels ranging from the low levels observed in an unstressed mouse during the
      daytime to levels significantly above those observed in mice during the night or
      as a result of stress. Adrenalectomy resulted in small increases in binding in
      hippocampus which was reversed by low dose corticosterone treatment. Chronic high
      dose corticosterone treatment resulted in significant decreases in binding in
      four of the eight brain regions examined. Similar, but not identical, results
      were obtained in two other mouse strains (C57BL and DBA/2). These results argue
      that corticosterone levels play an important role in modulating the level of the
      brain nicotinic receptors that bind alpha-bungarotoxin with high affinity.

PMID- 9157325
TI  - Intrathecal pituitary adenylate cyclase activating polypeptide facilitates the
      spinal nociceptive flexor reflex in the rat.
AB  - We have examined the effects of intrathecal (i.t.) pituitary adenylate cyclase
      activating polypeptide on the spinal nociceptive flexor reflex in decerebrate,
      spinalized, unanaesthetized rats. The flexor reflex was elicited by electrical
      stimulation applied subcutaneously to the sural nerve innervation area and
      recorded as electromyogram activity from ipsilateral hamstring muscles. Pituitary
      adenylate cyclase activating polypeptide(l-27) was administered over a wide dose
      range (10 ng to 10 mu g) and elicited a dose-dependent facilitation of the flexor
      reflex and did not depress the reflex at any dose. Furthermore, pituitary
      adenylate cyclase activating polypeptide did not inhibit the facilitation of the
      flexor reflex induced by repetitive stimulation of C-fibres. It is concluded that
      pituitary adenylate cyclase activating polypeptide had an excitatory effect on
      spinal cord function which may indicate a role for this peptide in nociceptive
      transmission and modulation. Moreover, in contrast to previous studies, we found
      no evidence suggesting that pituitary adenylate cyclase activating polypeptide
      exerts antinociceptive action at spinal level.

PMID- 9157326
TI  - Expression of alpha-, beta-, and gamma-subspecies of protein kinase C in the
      motor neurons in the embryonic and postnatal rat spinal cord.
AB  - Using polyclonal antibodies against alpha-, beta- and gamma-subspecies of protein
      kinase C, developmental changes in expression of these subspecies in the motor
      neurons in the rat cervical spinal cord were immunohistochemically investigated.
      On embryonic day-12, the motor neurons began to differentiate from
      undifferentiated neuroepithelial cells. On embryonic day-13, they began to
      express weak immunoreactivity for alpha- and beta-protein kinase C and slightly
      more evident immunoreactivity for gamma-protein kinase C. Immunoreactivity for
      protein kinase C in these neurons gradually became stronger, as the development
      progressed. Between embryonic day-18 and postnatal day-7, the motor neurons
      showed distinct immunoreactivity in the nucleus, perikaryal cytoplasm, axon and
      dendrites. At these stages, distribution and intensity of immunoreactivity for
      alpha-, beta- and gamma-protein kinase C were very similar. Thereafter, the
      expression of this enzyme in the nucleus gradually declined, while in the other
      structures, expression of each subspecies changed independently. On postnatal day
      28 and 35, expression of beta-protein kinase C in the axons was stronger than
      that of alpha- and gamma-protein kinase C, and immunoreactivity for gamma-protein
      kinase C in the perikaryal cytoplasm and dendrites was slightly weaker than that
      for alpha- and beta-protein kinase C. Expression of this enzyme in the motor
      neurons at these stages was almost the same as in the adult animal. Electron
      microscopically, immunoreactivity for protein kinase C was randomly distributed
      in the nucleus, and in the perikaryal cytoplasm, often near the cisterns of the
      endoplasmic reticulum. Expression of protein kinase C in the growing axons was
      quite different from that in the mature axons. In the dendrites, immunoreactivity
      for protein kinase C was distributed randomly in the cytoplasm and at the
      postsynaptic densities. These findings suggest that protein kinase C might
      regulate not only the neural functions, but also several aspects of the
      differentiation process in the motor neurons.

PMID- 9157327
TI  - Importance of protein kinase C for normal development of transmitter release
      properties in embryonic chick sympathetic neurons in culture.
AB  - The hypothesis that multiple trophic inputs are essential for normal development
      of transmitter release properties in sympathetic neurons was tested using two
      supportive agents (excess KCl and phorbol 12,13-dibutyrate which produce marked
      activation of protein kinase C and also support survival of chick sympathetic
      neurons in culture) in addition to nerve growth factor, ciliary neurotrophic
      factor and neurotrophin-3. Basal and electrically evoked (10 pulses at 1 Hz and
      10 Hz) release of [(3)H]norepinephrine from neurons supported by nerve growth
      factor was very high (1.5 to 2% of total [(3)H]norepinephrine content) and
      relatively insensitive to facilitation by tetraethylammonium as compared to
      release in neuroeffector organs, and the frequency-release response was negative.
      In K+-supported neurons, basal [(3)H]norepinephrine release was almost four-fold
      lower, evoked release was four- to eight-fold lower, the frequency response was
      flat to positive, and tetraethylammonium increased evoked release up to four
      fold. Inclusion of nerve growth factor in culture did not modify the effects of
      K+ on basal or evoked release, and nerve growth factor plus ciliary neurotrophic
      factor and/or neurotrophin-3 did not produce the changes observed in K+-supported
      neurons. Neurons supported by phorbol ester had a low background release, low
      evoked release, a positive frequency-release response, and 10- to 30-fold
      facilitation by tetraethylammonium of release evoked by 1 Hz or 1 pulse
      stimulation. Thus, physiological and pharmacological behavior of transmitter
      release of sympathetic neurons supported by excess KCl or phorbol ester was very
      similar to their counterparts growing in the body. Neurons supported by nerve
      growth factor showed an immediate rise in stimulated [Ca(2)+]i that was three- to
      five-fold above basal levels with either 1 Hz or 10 Hz stimulation. However, in
      phorbol supported neurons, [Ca(2)+]i rose gradually to about 1.5 times basal
      levels during 1 Hz stimulation and increased further with 10Hz stimulation.
      Tetraethylammonium had little effect on stimulated [Ca(2)+]i in nerve growth
      factor-supported neurons, but greatly facilitated the stimulated rise in
      [Ca(2)+]i in phorbol-supporte neurons. The data show that multiple trophic inputs
      distinct from nerve growth factor, neurotrophin-beta or ciliary neurotrophic
      factor are required for normal physiological function of sympathetic neurons.

PMID- 9157328
TI  - Identification of functional receptors for ciliary neurotrophic factor on chick
      ciliary ganglion neurons.
AB  - Ciliary neurotrophic factor and an avian homolog, growth promoting activity, are
      members of the cytokine/neurokine family of trophic factors and have been
      proposed to function as survival and developmental factors for ciliary ganglion
      neurons in vivo. Here we identify for the first time functional receptors for
      ciliary neurotrophic factor and growth promoting activity on cultured ciliary
      ganglion neurons. [(125)I]Rat ciliary neurotrophic factor binding studies
      indicate that rat ciliary neurotrophic factor and growth promoting activity bind
      to these receptors with a single affinity, while human ciliary neurotrophic
      factor recognizes both a high- and low-affinity site. Comparison of the relative
      potency of human ciliary neurotrophic factor and avian growth promoting activity
      in biological assays indicates that growth promoting activity is three to five
      times more active in promoting survival and in regulating acetylcholine
      receptors. The binding of ciliary neurotrophic factor is specific, sensitive to
      phosphatidylinositol-specific phospholipase C and partially inhibited by leukemia
      inhibitory factor, but not inhibited by other members of the human neurokine
      family, including interleukin-6, interleukin-22 and oncostatin M. Cross-linking
      of [(125)I]rat ciliary neurotrophic factor to ciliary neurons results in the
      specific labeling of three proteins with estimated molecular masses of 153,000,
      81,000 and 72,000. Only the 81,000 molecular weight component is released from
      the cells after treatment with phosphatidylinositol-specific phospholipase C,
      suggesting a membrane attachment via a glycosylphosphatidylinositol linkage.
      Stimulation with ciliary neurotrophic factor or growth promoting activity, but
      not by other neurokines, results in the rapid tyrosine phosphorylation of a
      90,000 molecular weight protein that is inhibited by pretreatment with
      phosphatidylinositol-specific phospholipase C. In conclusion, we report here the
      pharmacological and functional properties of ciliary neurotrophic factor
      receptors on embryonic ciliary ganglion neurons. These results provide the means
      for elaborating the molecular mechanisms of ciliary neurotrophic factor action
      and understanding its physiological role in a defined neuronal population.

PMID- 9157329
TI  - Optical studies of the biphasic modulatory effects of glycine on excitatory
      postsynaptic potentials in the chick brainstem and their embryogenesis.
AB  - Multiple-site optical recording of transmembrane potential activity, using a
      voltage-sensitive dye, was employed to monitor neural activity from the nucleus
      tractus solitarius of the chick embryo. Optical signals related to glutamate
      mediated excitatory postsynaptic potentials were evoked by a brief square current
      pulse applied with a microsuction electrode to the vagus nerve, and were recorded
      simultaneously from many sites in the brainstem slice preparation. We have found
      that glycine has biphasic modulatory effects on the glutamate-mediated excitatory
      postsynaptic potentials: at lower concentrations, glycine enhances the glutamate
      mediated excitatory postsynaptic potential-related optical signal, and at higher
      concentrations, it reduces the glutamate-mediated excitatory postsynaptic
      potential-signal. The enhancing effect was insensitive to strychnine, but the
      reducing effect was blocked by strychnine, suggesting that the former effect was
      induced by glycine which increased glutamate binding to N-methyl-D-aspartate
      receptors, and the latter resulted from an increase in chloride conductance
      through the strychnine-sensitive inhibitory glycine receptors in postsynaptic
      neurons. The inhibitory effect of glycine was first observed in the brainstem
      preparations at the seven-day-old embryonic stage, and the enhancing effect was
      first observed in the nine-day-old preparations. We determined regional
      distributions of the biphasic effects of glycine in the seven- to nine-day old
      embryonic preparations. The spatial distribution of the enhancing effect appeared
      to be concentrated on the ventral side of the nucleus tractus solitarius, and the
      inhibitory effect was relatively concentrated in the medial portion. Furthermore,
      we compared the glycine effect with the effect of Mg(2)+ on N-methyl-D-aspartate
      receptors, and we have found that the Mg(2)+ site is functionally organized prior
      to the glycine site during embryonic development.

PMID- 9157330
TI  - The synergism between metabotropic glutamate receptor activation and arachidonic
      acid on glutamate release is occluded by induction of long-term potentiation in
      the dentate gyrus.
AB  - In synaptosomes prepared from dentate gyrus, activation of the metabotropic
      glutamate receptor by the specific agonist, trans-1-amino-cyclopentyl-1,3
      dicarboxylate, increases release of glutamate in the presence of a low
      concentration of arachidonic acid. A similar interaction between trans-1-amino
      cyclopentyl-1,3-dicarboxylate and arachidonic acid is observed on inositol
      phospholipid turnover and on protein kinase C activity. We report here that when
      long-term potentiation is induced in the dentate gyrus by high frequency tetanic
      stimulation to the perforant path, the synergism between arachidonic acid and
      trans-1-amino-cyclopentyl-1,3-dicarboxylate is occluded. The occlusion of the
      synergistic action between arachidonic acid and trans-1-amino-cyclopentyl-1,3
      dicarboxylate on glutamate release extended to occlusion of the effect in
      inositol phospholipid turnover and protein kinase C activation in synaptosomes
      prepared from dentate gyrus in which long-term potentiation was induced in vivo.
      One interpretation of the results presented here is that tetanic stimulation is
      followed by stimulation of metabotropic glutamate receptors at a time when
      arachidonic acid concentration in the synaptic region is elevated, and that this
      interaction triggers the presynaptic changes required for expression of long-term
      potentiation.

PMID- 9157331
TI  - Dexamethasone rapidly increases calcium channel subunit messenger RNA expression
      and high voltage-activated calcium current in clonal pituitary cells.
AB  - Glucocorticoid hormones increase voltage-gated Ca(2)+ current density in clonal
      pituitary cells. To test whether these steroids might stimulate expression of
      Ca(2)+ channel genes, messenger RNase protection assays were used to measure
      alpha IC and alpha ID RNAs that encode pore-forming subunits of L-type Ca2+
      channels. We show here that dexamethasone rapidly increases alpha IC messenger
      RNA expression without affecting alpha ID messenger RNA level. This up-regulation
      of channel messenger RNA is also produced by natural glucocorticoids and is
      blocked by the glucocorticoid antagonist Ru48386. The up-regulation of the
      channel subunit messenger RNA expression is associated with an increase in high
      voltage-activated Ca(2)+ current density. Thus, glucocorticoids may produce a
      long-term effect on Ca(2)+ homeostasis in clonal pituitary cells by
      differentially regulating expression of Ca(2)+ channel subunit genes.

PMID- 9157332
TI  - Apomorphine and dopamine D(1) receptor agonists increase the firing rates of
      subthalamic nucleus neurons.
AB  - The present study investigated the regulation of spontaneous neuronal activity in
      the subthalamic nucleus by dopamine receptors using in vivo extracellular single
      unit recording techniques. Subthalamic nucleus neuronal firing rates were doubled
      by systemic administration of the nonselective dopamine receptor agonist
      apomorphine. The response to apomorphine was attenuated in animals anesthetized
      with chloral hydrate or ketamine. The dopamine D(2)/D(3) receptor agonist
      quinpirole did not alter subthalamic nucleus neuronal firing rates. Firing rates
      were increased by the D(1) receptor agonists SKF 38393 and SKF 82958 two- to
      three-fold; these increases were reversed by the D(1) receptor antagonist, SCH
      23390. Autoradiographic studies using [(125)I]SCH 23982 indicated that D(1)
      family receptors were located along the ventral edge of the subthalamic nucleus
      and the dorsal aspect of the cerebral peduncle. Local administration of SKF 82958
      into the subthalamic nucleus doubled neuronal firing rates; these increases were
      reversed by systemic administration of SCH 23390. Infusion of SCH 23390 into the
      subthalamic nucleus prevented systemic SKF 38393 from increasing the firing rates
      of subthalamic nucleus neurons. These results indicate that apomorphine and D(1)
      receptor agonists exert an excitatory influence on subthalamic nucleus neuronal
      activity. In addition, the excitation induced by D(1) receptor agonists appears
      to be mediated, at least in part, by D(1) receptors located in the vicinity of
      the subthalamic nucleus. The data suggest that basal ganglia output under
      conditions of increased dopamine receptor stimulation is influenced by the
      activation of excitatory subthalamic efferent pathways, as opposed to suppression
      of these pathways as predicted by current models of basal ganglia function.

PMID- 9157333
TI  - Revised cutoff values of serum aminotransferase in detecting viral hepatitis
      among CAPD patients: experience from Taiwan, an endemic area for hepatitis B.
AB  - BACKGROUND: To determine the best cutoff values of aspartate aminotransferase
      (AST) and alanine amino-transferase (ALT) in detecting viral hepatitis C
      infection among patients of continuous ambulatory peritoneal dialysis (CAPD).
      METHODS: 90 (44 male and 46 female) CAPD patients and 526 adult controls (266
      male, 260 female) were enrolled. Serum AST and ALT were measured by an auto
      analyser monthly. Serum HBsAg was examined using a RIA method and anti-HCV by an
      second-generation EIA method. The best cutoff values of AST and ALT for detecting
      viral hepatitis were obtained from the ROC (receiver-operating characteristic)
      curve. RESULTS: The prevalence of anti-HCV(+) was significantly higher in CAPD
      patients (16.7%) than in normal controls (4.9%), while that of HBsAg(+) was
      similar in both groups. CAPD patients had significantly lower levels of serum
      aminotransferases compared to normal controls. Mean AST were 23.8 IU/l in normal
      control and 18.8 IU/l in the CAPD patients (P < 0.001). Mean ALT were 21.9 IU/l
      in normal controls and 15.3 IU/l in the CAPD patients (P < 0.001). CAPD patients
      with HCV infection had higher serum AST and ALT levels than those without.
      However, HBV infection did not cause significant serum aminotransferase elevation
      in patients. The conventional cutoff values of AST (40 IU/l) and ALT (40 IU/l)
      for detecting viral hepatitis yielded only a sensitivity of 27.3 and 18.2%
      respectively; on the contrary, our revised cutoff values of AST (24 IU/l) and ALT
      (17 IU/l) had better sensitivities (AST, 72.7%; ALT, 63.6%). For serial
      aminotransferase values, the sensitivity of AST and ALT for detecting HCV were
      36.4 and 27.3% by conventional criteria, and were both 81.8%, by our newly
      revised criteria. CONCLUSIONS: Serum aminotransferase cutoff values should be
      modified for screening viral hepatitis in a CAPD population. Our new cutoff
      criteria had important clinical implications in providing benefits of earlier
      detection and possible prevention from chronic hepatic deteriorations.

PMID- 9157334
TI  - [Immunopathologic disorders in atopic dermatitis].
AB  - The atopic dermatitis is a multifactorial inheritable disease, in which
      pathogenesis in addition to environmental factors (climate, allergens, clothing)
      genetically determined multiplex metabolic differences (arachidonic acids,
      essential fatty acids) and immunologic alterations play an important role. Within
      immunologic findings the disturbances of balance in Th1 and Th2 subclasses, the
      increased degranulation activity of mast cells and the increased antigen
      presentation activity of Langerhans cells can be stressed. The clinical
      immunological alterations shown in the diseases, the increased production of IgE
      and so the type I. allergic reactions (urticaria, gastrointestinal manifestation
      of food allergy, allergic rhinitis, asthma bronchiale), the difference of
      cellular immunity of the skin can be explained by the above mentioned main
      immunological changes. In understanding of immunological origin of atopic
      dermatitis the IgE receptors expressed on the surface of Langerhans cells
      (connecting the immediate and delayed type of immune response) mean significant
      help.

PMID- 9157335
TI  - [The role of computerized tomography in the staging of lung cancer].
AB  - Staging of lung cancer place significant role in the prognosis and treatment of
      the disease. Beside bronchoscopy, CT one of the important method for the tumor
      staging. 135 CT examinations with diagnosis of suspected lung cancer were
      evaluated and radiologic diagnosis was compared with the cyto-histological and
      surgical results. In 112 cases both CT and histological diagnosis were performed:
      both method revealed malignant tumors in 108 cases. Five lesions were regarded as
      tumour by CT but histological result proved aspergilloma, or specific processes.
      Abnormal lymph nodes were recognised at 98 tumours patients. There was a good
      correlation-regarding the number, size measurement-between CT and surgery.
      Histological diagnosis proved that all of the lymph nodes larger, then 2 cm of
      diameter contained metastic cells. In the 1-2 cm size almost all of the lymph
      nodes were metastatic. In addition tumour cells were found in some lymph nodes
      smaller, than 1 cm, too. This gives warning sign: smaller lymph nodes need more
      attention than we assumed. CT prove to be confident method for the evaluation,
      measurement and localisation of the tumours and lymph nodes in the chest.

PMID- 9157336
TI  - [Treatment of pancreatic insufficiency with a preparation containing high lipase
      activity].
AB  - In vitro testing of lipase survival of Panzytrat 25,000 homogenized in Tris HCl
      buffer and Lundh meal stimulated gastric or duodenal contents demonstrated
      favorable stability of lipase of this new preparation in the protein and fat
      containing gastric and duodenal juices of patients with chronic pancreatitis.
      Later an open, intra-individually controlled study with two doses of Panzytrat
      25000 (5 x 1 and 5 x 2 capsules/day) was performed in 10 patients with severe
      pancreatic steatorrhoea. A diet containing 70 g of fat/day was offered and the 3
      day fat loss of collected stools was measured in the last 3 days of 5-day
      equilibration periods with and without replacement therapy. After these short
      term periods, patients were treated with 5 x 1 capsules of the drug for one month
      and body weight increases as well as patient's appraisals were registered. Stool
      weight and fat loss maximally decreased already in response to the 5-day
      treatment with 5 x 1 capsules of drug and double dose of the preparation did not
      further decrease steatorrhoea in most cases except 2 patient. Disappearance of
      fat loss was achieved in 3 out of ten patients. Body weight of patients increased
      in most cases and their subjective evaluation was also favorable.

PMID- 9157337
TI  - [How great is the risk of personal contact in the transmission of hepatitis C
      virus infection?].
AB  - The sexual, household and nosocomial transmission of Hepatitis C virus infection
      were studied in patients with HCV-RNA positive chronic active hepatitis,
      confirmed by PCR. Liver function tests and hepatitis C virus serology were
      performed in family members living in the same household of patients, sexual
      partners as well as members of the hospital environment in the Department of
      Hepatology. Fifty-three members of 27 families and 32 staff-members were
      examined. Quantitative HCR-RNA-PCR and virus serotype of anti-HCV (III.gen.)
      positive individuals were also identified. Two of the family members turned out
      to be anti-HCV positive. The husband in one of the married couples was treated
      for hepatitis of unidentified etiology in an Infectology Department four years
      ago. His wife was found to have chronic hepatitis C since two years. They both
      had C virus of serotype 1. The mother and daughter in another family suffered
      from von Willebrand factor deficiency syndrome. It was documented that they were
      infected by blood transfusion at different occasions. Their C virus serotypes
      were different. All the staff members of Hepatology Department were anti-HCV
      negative. These results confirmed the possibility of the non-parenteral
      transmission of hepatitis C virus, however, its incidence is very low.

PMID- 9157338
TI  - [Human parvovirus B19 infection in a child suffering from chronic arthritis].
AB  - The pathogenicity of the human parvovirus B19 has been disclosed in the last two
      decades. Different syndromes (erythema infectiosum or hydrops fetalis) can be
      produced by this virus as well as aplastic crisis in patients with haemolytic
      anaemia. It is a common infection both in adults and in children. The frequency
      of joint symptoms in erythema infectiosum is about 8% in childhood but tenfold of
      it in the adults. However, the arthropathy could be the only symptom without
      constitutional complains or rash. The joint problems used to be solved after some
      weeks in most cases but occasionally they could keep for some months or years.
      The disease is thought to be rheumatoid arthritis if the possibility of a
      parvovirus B19 infection has not been considered. In this paper the authors
      present a case report of a 14 years old boy with fever of unknown origin, skin
      eruptions and arthritis. On that connection, they discussed the recent knowledge
      about the human parvovirus B19 and refer to its importance in differential
      diagnosis of joint problems.

PMID- 9157339
TI  - [Mihaly Pekar and the Erzsebet University of Scienses at Pecs].

PMID- 9157340
TI  - [Markusovszky and health care for students and youth].

PMID- 9157341
TI  - [Spiral CT: new clinical indications and special artifacts].
AB  - Authors describe the technical principles of volumetric CT, in comparison with
      the conventional method. New, quick data acquisition related artifacts are
      demonstrated in the different organs in order to avoid diagnostical faults.
      Details are given about the special examination parameter settings which are used
      for searching for particular pathological processes. Advantages, disadvantages,
      physiological and technical limitations are discussed. Authors present the new
      clinical applications, especially in the field of vascular and musculoskeletal
      imaging.

PMID- 9157342
TI  - [Steroid hormone receptors in squamous cell carcinoma of the head and neck].
AB  - In this study we have tried to find new prognostic markers to extend the
      therapeutical modalities for patients with head and neck squamous cell carcinoma.
      During evolution the development of the pharyngolaryngeal region differs in males
      and females, therefore this region can be considered as one of the target organs
      for sex steroids. Some of the tumours, originating from this area, contain
      hormone receptors that theoretically makes them susceptible for hormone therapy.
      Therefore the real concentration of steroid receptors is of great clinical
      importance. We determined the estradiol, progesterone and testosterone receptor
      content using biochemical method in tumour tissue of 33 male patients with head
      and neck squamous cell carcinoma. The receptors in the macroscopically intact
      mucosa in 15 of all tumour cases were also measured. The patients were followed
      for 18-24 month after operation and postoperative irradiation performed according
      to the protocol of the Head and Neck Surgery department. There were 26/33 (79%)
      estradiol receptor positive, 14/33 (42%) progesterone receptor positive and 18/30
      (60%) testosterone receptor positive cases among the tumour samples. The healthy
      mucosa samples were positive in 6/15 (40%), 2/15 (13%) and 3/15 (20%) of cases,
      respectively. The differences in proportion of positive status between tumour and
      healthy mucosa was statistically significant. We established that during the
      control period the highest rate of the tumour-free survival was in the estradiol
      receptor positive, progesterone receptor negative group. Consequently the steroid
      receptor status of head and neck squamous cell carcinomas might help in assessing
      the prognosis of survival, and in possible choice for endocrine treatment, in
      order to complete the complex tumour therapy.

PMID- 9157343
TI  - [Prion dementias: nosology and diagnostic difficulties in the spectrum of
      Creutzfeld-Jakob encephalopathy].
AB  - Creutzfeldt-Jakob disease (CJD) is one form of subacute prion diseases with
      spongiform encephalopathy. Hereditary, infectious and sporadic types of the
      disorder can be distinguished. The abnormal transformation of the prion protein,
      relevant in the normal synaptic transmission is considered as an important factor
      in the development of this disease. Gerstmann-Straussler-Scheinker syndrome (GSS)
      and familial fatal insomnia (FFI) are the other diseases belonging to the same
      disease spectrum. The common feature of these disorders is that the different
      mutation of the same prion protein could result in different phenotypes and
      symptoms. CJD is considered as a neurologic disorder but the clinical symptoms
      and differential diagnosis of the disease are also relevant problems in
      psychiatry. Because of the early onset of dementia and the psychotic and delusive
      symptoms, the patients with CJD are frequently admitted to psychiatric wards.
      Recently worldwide public interest has been focused on prion dementias because of
      the possible human transmission of bovine spongiform encephalopathy in the UK.
      The diagnostic problems of our seven CJD patients diagnosed since 1991 in the
      catchment area of Szeged city are discussed in the view of recent findings of
      molecular biology, nosology, diagnostic and therapeutic problems of this
      devastating disease.

PMID- 9157344
TI  - [Cytokines in experimental acute pancreatitis].
AB  - The authors induced acute necrotizing pancreatitis in Wistar rat by intraductal
      injection of taurocholic acid (150 microliters or 200 microliters 6%). Plasma
      values of amylase, TNF, IL-6 levels and wet pancreas weight/body weight ratio
      have been determined. Histologic analysis of pancreas proved severe acute
      necrotizing pancreatitis with microabscess formation and beginning respiratory
      distress syndrome was observed in the lungs, TNF and IL-6 levels increased
      significantly after administration of 200 microliters 6% taurocholic acid. The
      authors emphasise the importance of cytokines in the development of acute
      necrotizing pancreatitis.

PMID- 9157345
TI  - [Successful multi-step management of developmental heart defects after
      intrauterine diagnosis].
AB  - At 28th week of gestation a conotruncal malformation with ventricular septal
      defect was diagnosed by fetal echocardiography. Postnatal echocardiographic and
      angiocardiographic examinations confirmed the diagnosis of conotruncal
      malformation (pulmonary atresia, ventricular septal defect, patent ductus
      arteriosus, aortopulmonary collateral arteries). The unifocalization (age: 11
      months) and total correction with aortic homograft (age: 7 years) were performed.
      To our knowledge our case is the first whose intrauterine diagnosis of complex
      congenital heart disease was confirmed after delivery and had successful two
      stage surgical management.

PMID- 9157346
TI  - [Remembering Prof. Geza Krepuska].

PMID- 9157347
TI  - [The Budapest Irgalmas Hospital and the 45-year-old Urology Department of the
      ORFI (National Institute for Rheumatology and Physiotherapy)].

PMID- 9157348
TI  - [Distortion of the past history of the profession does not help to bring the
      profession up-to-date].

PMID- 9157349
TI  - [Ceramic-to-ceramic combination. Relic or renaissance?].
AB  - More than 20 years after the introduction of the alumina-alumina bearing system
      for total hip replacements (THRs) in Germany, this combination still only
      accounts for a small percentage of the conventional combinations with
      polyethylene cups. Follow-up examinations of ceramic-ceramic THRs with early
      alumina quality result in an extreme range of linear wear rates from 30 nm to 3.7
      mm per year. Simulator tests confirm the potential for minimal debris generation
      but also show the sensitivity of the system to malpositioning and un-smooth
      repositioning.

PMID- 9157350
TI  - [Cementless fixation of the endoprosthesis using trabecular, 3-dimensional
      interconnected surface structures].
AB  - While the principle of enlarging the surface area has been recognized and used in
      different ways for some time, there is often no schematic, detailed description
      or fundamental research. Taking a surface structure consisting of trabecular
      three-dimensional connecting elements, essential parameters are shown, making it
      clear that the flexible dynamic reaction of the effective "anchoring space" with
      a suitable specified shape (construction height, alignment, network) can be
      reproducibly shaped and used. This has led to a hip endoprosthesis with a
      graduated surface structure. The construction height of the trabecular structure
      varies, decreasing from proximal to distal.

PMID- 9157351
TI  - [Comparative tribological studies of Chirulen, Hylamer and Enduron combined with
      A1203].
AB  - The creep and wear behaviour of Chirulen, Hylamer and Enduron, materials which
      differ only in their manufacturing procedures, was examined and compared.
      Chirulen is manufactured by being pressed into form by plates, whereas Hylamer
      and Enduron are shaped by tubes. Hylamer differs from Enduron in that
      intermediate material processing is undertaken with the goal of improving the
      initial material. The wear and deformation rate was determined by means of the
      ring-on-disc testing device after 360,000 cycles and after 1.0 x 10(6) cycles,
      respectively. The static tests for the determination of wear were carried out at
      a contact stress of 5.62 MPa and a testing time of 100 h in analogy to the ring
      on-disc tests. Chirulen and Hylamer demonstrated comparable wear with a tendency
      toward a lower wear rate in Hylamer, while Enduron presented a clearly higher
      wear rate.

PMID- 9157352
TI  - [In-vivo wear of the slide combinations ceramics-polyethylene as opposed to metal
      polyethylene].
AB  - The present study deals with long-term dimensional changes in cemented Muller
      type total hip endoprostheses. Creep and wear contribute to different extents to
      the dimensional changes in polyethylene. The total amount of polyethylene wear is
      represented by the displacement of the femoral head into the socket. Within the
      first postoperative years, the head shifts up to a relatively high rate of about
      0.5 mm per year. This rate diminishes after 5 years to an average of about 0.1 mm
      (ceramics) and 0.2 mm (metal) per year. Values exceeding 0.2 mm per year for the
      shift of the femoral head are considered to be unfavourable with regard to a
      probable loosening of the prosthesis. In this study we determined the orientation
      of the centre of the prosthetic head in relation to the wire marker of the
      polyethylene cup, comprising in all 369 total hip prostheses. After an average of
      77 months, 96% of the prostheses with ceramic heads (n = 109) had a wear rate of
      less than 0.2 mm per year. Using metal heads (Protasul-2 and Protasul-10) this
      rate could only be measured in 71% (n = 109) of the prostheses (61.5 months). The
      combination ceramics-polyethylene produces half of the total amount of wear
      produced by metal-polyethylene. Younger patients should preferably be treated
      with a ceramic ballhead.

PMID- 9157353
TI  - [Experimental studies of metal-metal slide combinations and their value in
      relation to expected in-vivo behavior].
AB  - A simulator test was carried out in the hip joint simulator on a metal-on-metal
      coupling of a modified CoCrMo alloy. The test was run up to 1.9 million cycles
      and the tribological behaviour of the coupling was documented by means of
      roundness measurements and scanning electron microscopy. It is seen that the
      tribological system metal on metal is characterized by mixed friction in the
      artificial hip joint, thus generating material contacts that are documented by
      the roundness variation and by the SEM contact zone analysis, showing "three
      body" wear of this system. The roundness variations indicate that running-in wear
      is to be noticed at first with a decreasing tendency over the 1.9 million cycles.
      Nevertheless, this observation does not allow any prognosis as to the wear rates
      in the case of a higher number of cycles. It must be taken into consideration
      that aqua destillata had to be used as a lubricant for technical reasons; the use
      of serum/Ringer solution might have produced different results. Further
      investigations in the hip joint simulator and on revised metal-on-metal couplings
      will be carried out in this respect.

PMID- 9157354
TI  - [Changes in shape of the McKee-Farrar hip endoprosthesis].
AB  - The still unsolved problem of aseptic loosening in total hip arthroplasties with
      identification of polyethylene wear particles as one of its major causes, has led
      to reintroduction of metal-to-metal articulations, as indicated by a few good
      clinical long-term results with all-metal McKee-Farrar arthroplasties. In this
      paper, data on 145 patients from a population of more than 1400, all with
      implanted McKee-Farrars, who underwent revision surgery for aseptic loosening,
      are collected and analysed for dependence of duration to brands of the implants
      and position of the cups. The surface of each of 55 revised implants was measured
      using a 3-D device. The results showed no interdependence between time of
      loosening, brand inclination of the cup and deviation in shape of ball and cup.
      Additionally, the deviations in shape were slight.

PMID- 9157355
TI  - [Tribological properties of carbon fiber-reinforced plastic. Experimental and
      clinical results].
AB  - Wear of the articulating components (especially PE-UHMW) of total hip
      endoprostheses is the most important technical factor limiting the functional
      lifetime. To minimize wear debris, ceramic heads, according to ISO 6474 (Al2O3),
      have been used, from 1969 paired with Al2O3 and since 1975 paired with PE-UHMW.
      Al2O3 balls articulating with cups made from CFRP have been in clinical use since
      1988. Laboratory experiments and in-vivo testing showed minimized wear debris and
      mild biological response to wear products using CFRP (carbon fiber reinforced
      plastic) instead of PE-UHMW as the cup material. The articulating surfaces of
      retrieved ceramic heads (Al2O3-Biolox) and cementless CFRP cups (carbon fiber
      reinforced plastic, Caproman) were compared using sphericity measurement
      techniques, scanning electron microscopy (SEM) and roughness measurements
      (including advanced roughness parameters Rvk or Rpk according to ISO 4287).
      Altogether, the first results of the clinical study showed that the combination
      Al2O3-ball/CFRP-cup came up to the expected lower wear rates compared with the
      conventional combinations. The wear rates are comparable with the combination
      Al2O3/Al2O3 without the material-related problems of ceramic components in all
      ceramic combinations.

PMID- 9157356
TI  - [Safety aspects in the coating of titanium slide components].
AB  - Due to the ever increasing percentage of patients who suffer from allergies and
      need joint replacements, it is necessary to also consider using titanium for the
      bearing surface. Hence, the number of coated titanium bearing surfaces for both
      hips and knees is increasing. It is difficult for the user to evaluate the
      products already marketed. This paper describes the presently used coating
      techniques without considering sophisticated technical details but listing the
      advantages and disadvantages of the various technologies. Using the list of
      necessary basic investigations for qualifying a coating together with production
      relevant measures for quality assurance, this paper aims to provide the
      possibility to get involved with a supplier in a discussion about the suitability
      of the coated titanium bearing components without regarding the specific
      technical details.

PMID- 9157357
TI  - [Comparative experimental studies on rigidity, deformation and blunting behavior
      of various total hip endoprostheses under dynamic load].
AB  - The biomechanical reasons for moving and loosening of the acetabular cup and
      femoral prosthesis are still unclarified. Especially, chronic and mechanical
      overloads of the interfaces, which are caused by the change of stiffness and
      damping properties of the whole system, cannot be excluded. To date, the
      description of dynamic behaviour of hip-joint endoprostheses from the viewpoint
      of material selection and design is insufficient. On the basis of comparative
      experiments, this publication aims to complete the knowledge about mechanical
      properties of artificial hip joints. Primarily, we focused on the quantitative
      registration of certain influences (e.g. design, dimensions and material) on the
      dynamic properties of different kinds of acetabulum cups. Therefore, a
      significant new test method was developed for this examination. Conventional test
      methods work according to the principle of constancy of maximum forces and
      excitation frequencies. They do not consider the forces of inertia resulting from
      body mass, even though these reaction forces are decisive for the dynamic
      properties and mechanical behaviour of the components of endoprostheses. A
      selection of representative implants from several manufacturers were tested
      according to the new test method, which is based on the "mass-spring, absorber"
      principle. The examined prostheses concerned differed in material, method of
      fixation and geometric dimensions. The results of these examinations give clues
      to the repercussions of the mentioned parameters on the dynamic behaviour of
      endoprosthetic systems. In order to evaluate the results, hip joints from animals
      were also examined and provided relevant information for desirable alternative
      solutions to the problem in view of construction and material.

PMID- 9157358
TI  - [Contact surface and pressure load at implant-bone interface in press-fit cups
      compared to natural hip joints].
AB  - The implantation of an endoprosthetic socket into the acetabulum alters the
      mechanical stresses in the periacetabular region in a significant manner compared
      with the natural hip joint. In this way, a remodelling process is initiated.
      Primary stability to achieve osseointegration and a loading of the acetabulum
      owing to the biomechanical interaction between cup and bone that is similar to
      the natural joint, are important prerequisites for a long-term bony integration
      of the implant. Therefore, the intra-articular pressure distribution in eight hip
      joints of fresh-frozen human pelvic cadavers and in the bone/implant interface of
      two press-fit cups was investigated using pressure-sensitive Prescale films. A
      modular cup with a pure hemispherical shape (PCA cup) and a monoblock cup with a
      biradial surface and flattening of the pole (press-fit cup) were tested. Loads of
      up to twice body weight were introduced into the sacrum, simulating a single-leg
      stance with the hip in neutral flexion. The results were extracted from the
      pressure prints applying digital image processing methods. It was demonstrated
      that intra-articular contact occurs over the whole articular surface of the
      joint, with contact areas between 39.0% and 56.9% of the hemisphere, showing
      zones of higher pressures where the acetabulum is supported by the iliac, ischial
      and pubic bone. The biradial press-fit cup showed mean contact areas of 44.7% of
      its surface when inserted under press-fit only. This area was enlarged to 53.0%
      and to 64.2% with increasing load. The corresponding figures for the PCA cup are
      45.1%, 48.9% and 57.1%. The low-profile PCA cup produces a small band of high
      pressure near the periphery, and with increasing load its pole area comes into
      contact with the acetabular fossa. Occasionally, irregular gaps do occur. The
      press-fit cup enlarges the contact area from the periphery to the pole within its
      optimised biradial contact zone until the lunar surface is loaded. The acetabular
      fossa remains unloaded owing to the flattening of the pole. This load
      distribution is close to that of the natural hip joint. The pressure distribution
      of both cups is also characterised by three zones at the iliac, ischial and pubic
      bones showing a higher load transmission.

PMID- 9157359
TI  - [Meniscus lesions].

PMID- 9157360
TI  - [Skin and neuromediators].

PMID- 9157361
TI  - [Structure and functions of the cutaneous nervous system].
AB  - Cutaneous nerves are either somatic sensory afferents to ganglion neurons or
      terminal efferents from the autonomous nervous system. Myelinated somatic nerves
      form subcutaneous and intradermal plexus from which arise various types of
      endings: free, dilated and included in corpuscles. Free terminals are ramified in
      the dermis, epidermis and the epithelial sheet of hairs. Dilated terminals are
      lanceolate fibres around hairs and those in close contact with Merkel cells. Well
      identified corpuscles are those of Meissner, Ruffini and Pacini. Physiologically,
      nerves are involved as mechano-, thermo- and pain receptors. Five
      mechanoreceptors are recognized according to their rate (slow/fast) of adaptation
      and their receptive field (type I, small; type II, large): Merkel cells (SA I),
      Ruffini corpuscles (SA II), Meissner corpuscles (FA I), Pacini corpuscles (FA II)
      and palisades of lanceolate nerve endings (FA with various field units). Thermo-
      and nociceptors are mainly thin unmyelinated free nerve endings with various
      rates of conduction velocity. The autonomic nervous system supplies sympathetic
      innervation appearing as unmyelinated small nerve endings in close contact with
      skin appendages, except sebaceous glands. Only sweat glands are innervated by
      cholinergic terminals.

PMID- 9157362
TI  - [Development of the cutaneous nervous system].
AB  - Skin of vertebrates is richly innervated, mainly by sensory nerve fibres which
      form a well organized pattern, particularly around phaners. This innervation
      develops segmentally (dermatomes) from cutaneous branches provided by spinal
      nerves. The innervation begins at 13 days (E 13) in the mouse embryo and,
      although hair buds form at E 16, follicles are only innervated from 5 days
      postnatally being complete at about 20 days. In the chick skin, innervation forms
      a regular and characteristic pattern around feathers, and can be visualized on
      whole mounts. Its development can be traced from 6 days of development in
      relation to feather morphogenesis. Experiments producing non formation of spinal
      ganglia (X-ray irradiation or neural tube ablation) or production of neoapteria
      (hydrocortisone treatment) or ectopic feathers on scales (retinoic acid
      treatment) show there is a close link between feather development and nerve
      pattern formation. In vitro co-cultures of dorsal root ganglia and epidermis
      combined with the use of synthesis inhibitors and antibodies, showed that
      epidermis has a repulsive effect on nerve fibres mediated, at least in part, by
      chondroitin sulphate proteoglycans. These compounds have been localized, using
      antibodies mainly at the base of the feather buds and seem to play a key role in
      the construction of the fine nerve pattern around feather follicles. In
      conclusion, the specific nerve patterns are the final result of selective
      responses of growing nerve endings to unique combinations of local cues and
      conflicting interactions which are developmentally regulated in parallel with the
      morphogenesis of phaners.

PMID- 9157364
TI  - Neuropeptides, nerve growth factor and the skin.
AB  - Cutaneous nerve fibers can modulate inflammatory reactions through local release
      of neuro-peptides (NP). In fact, NP are able to regulate both acute and chronic
      aspects of cutaneous inflammatory processes, such as vascular motility, cellular
      traffic-king, activation and trophism. Several experimental evidences suggest a
      participation of NP to the pathogenesis of inflammatory dermatoses: in
      particular, modulation of inflammatory reactions in the skin can be obtained
      through pharmacologic manipulation of the neuropeptidergic system. Furthermore,
      evidence of local alterations of NP levels in inflamed skin has been obtained. It
      has been hypothesized that the inflammatory process induces reactive changes in
      the neuronal NP content. The primary candidate as mediator of this neuronal
      recruitment in the course of inflammatory reactions is the neurotrophin nerve
      growth factor, that is produced in the skin in increased amounts during
      inflammatory processes and may regulate peptidergic synthesis at a neuronal
      level.

PMID- 9157363
TI  - [Merkel cell and neuro-cutaneous system].
AB  - The Merkel cell is an epidermal neuroendocrine cell that can be identified by
      electron microscopy based on its neurosecretory granules or by immunolabeling
      based on its pattern of cytokeratin expression. Its origin is controversial but
      may be epidermal rather than neural. Although its functions have not been
      completely elucidated, there is strong evidence that it produces neuromediators,
      is involved in the perception of mechanical stimuli, exerts trophic and
      attractant effects on nerves, stimulates keratinocyte proliferation and
      differentiation, and plays a role in the spatial organization of the epidermis
      and epidermal appendages.

PMID- 9157365
TI  - [Substance P and human skin].
AB  - Substance P (SP) is a neuropeptide that is a neurotransmitter and a
      neuromodulator in the central and peripheral nervous system. SP is known to have
      regulatory effects on nervous or non nervous cells, including immune cells. SP is
      involved in the physiopathology of local inflammation, including inflammatory
      dermatoses. The purpose of this review is to relate the localization of SP and
      its receptors to illustrate the immunomodulatory functions of SP through its
      effects on various immune cells and to focus on the localization of SP in human
      skin and on its effects on cutaneous cells. The probable implication of SP in
      inflammatory dermatoses will be discussed.

PMID- 9157366
TI  - [Neuro-immuno-cutaneous system (NICS)].
AB  - The concept of neuro-immuno-cutaneous system (NICS) means narrow interrelations
      between nervous system, immunity and skin. Indeed, there are numerous cellular
      contacts between nerve fibers, cutaneous cells and immune cells; cutaneous cells
      can synthesize neuromediators and they express receptors to these molecules;
      neuromediators are able to modulate functions of cutaneous and/or immune cells.
      Using confocal or electron microscopy, connexions between nerve fibers and
      cutaneous cells have been observed. In the skin, nerve fibers may secrete
      neuromediators: substance P, vaso-active intestinal peptide (VIP), somatostatin,
      calcitonin-gene related peptide (CGRP), gastrin-releasing peptide (GRP),
      neuropeptide Y, peptide histidine-isoleucine (PHI), neurotensin, neurokinins A et
      B, bradykinin, acetylcholine, catecholamines, endorphins and enkephalins.
      Neurohormones such as prolactin, melano-stimulating hormone (MSH) or adreno
      corticotrophic hormone (ACTH) are also expressed in the skin. Neuromediators and
      neurohormones are also secreted by cutaneous cells and these cells express
      receptors. Functions of epidermal or dermal cells are modulated by these
      substances. Immune cells transiently present in the skin (macrophages,
      lymphocytes...) are modulated by neuromediators through receptors. In the course
      of skin diseases, especially inflammatory diseases, the NICS is destabilized.
      Psoriasis and atopic dermatitis are good examples. This phenomenon might be due
      to inflammation but is also responsible for induction and maintenance of the
      inflammation.

PMID- 9157367
TI  - [Skin and stress].
AB  - The concept of stress was developed based on data from experimental pathology and
      psychology studies. Selye defined stress and described the physiologic changes
      induced by stress, under the designation "general adaptation syndrome". The
      interactive aspect of stress has since then been emphasized. Stress results from
      a unique interaction between a thinking individual and a physical or social
      environment. The presence in humans of a mental apparatus capable of thinking,
      reminiscing, and fantasizing accounts for the specific features of stress as a
      clinical condition. It follows that psychosomatic dermatology cannot be satisfied
      with defining and documenting stress, with establishing a link between stress and
      a disorder of the skin (an organ that plays a unique role in communication), and
      with evaluating the biological mechanism underlying the skin lesions. Another
      essential goal is to understand why an individual patient, with his or her unique
      history, develops a skin disorder as a manifestation of an inability to cope with
      adversity. Two psychologic factors should be taken into account in dermatology,
      namely stress and the personality of the person subjected to the stress. What
      makes a life event stressful is often the personality of the subject experiencing
      the event.

PMID- 9157368
TI  - [Stress and skin: experimental approach].
AB  - The effects of electric stress on epidermal cell mitosis, sebum production, hair
      growth and tumor induction, was studied in laboratory using Maynert and Levi's
      technique: reproducible electric stimulations were delivered in mice or hamsters
      in order to induce standardised stress. Such repeated stimulations increase
      cutaneous catecholamine concentrations in the early period. Repeated stress
      induce a decrease in keratinocyte and melanocyte mitoses, an increase of
      sebaceous excretion, and favours the development of outset of photoinduced
      tumors. The possible involvement of these data in human dermatopathology and
      clinical dermatology are discussed for each impaired cutaneous function: mitoses,
      hair growth, sebaceous function and anti-tumoral immunity.

PMID- 9157369
TI  - [Neuromediators in dermatology. Therapeutic prospectives].
AB  - Neuropeptides are neurotransmitters and neurohormones that play a role in various
      cutaneous functions. Keratinocytes and dermal endothelial cells are able to
      synthesize neuropeptides which are transported by nerve fibers or immune cells.
      Specific receptors for neuropeptides are also present on cutaneous cells.
      Neuropeptides intervene as neurogenic modulators of inflammatory reactions and
      therefore participate in the pathogenesis of skin diseases. An increasing body of
      evidence supports the setting up of clinical trials using topically neuropeptide
      agonists and/or antagonists in the treatment of chronic inflammatory skin
      disorders such as post-herpetic neuralgia, prurigo nodularis, localized pruritus,
      psoriasis, atopic dermatitis, contact dermatitis, cold urticaria, nostalgia
      paresthetica, diabetic neuropathy, Raynaud's phenomenon. In the near future,
      neuropeptides will represent a new approach to skin therapy.

PMID- 9157370
TI  - [Effect of research conditions on succinate oxidation in brain mitochondria in
      circulatory hypoxia].
AB  - The purpose of the study was to examine the pattern of changes revealed in the
      metabolic reactions in the cerebral mitochondria, oxidizing succinates in acute
      circulatory hypoxia under the influence of hyper- and normoxic conditions of an
      experiment. Following 3.5 hours of acute circulatory hypoxia in the cerebral
      mitochondria which were resistant to bilateral carotid occlusion, rats showed
      increased succinate-dependent energy production, followed by compensatory
      inhibition of succinate dehydrogenase. The normoxic conditions of the cerebral
      mitochondrial investigations preserved succinate-dependent and transaminase
      respiratory fractions of organelles which were inhibited under hyperoxic
      conditions of an experiment. This improves more objective assessment of the
      responses of the mitochondrial oxidation system on the pathology model under
      study.

PMID- 9157371
TI  - [Study of the protective effects of phenothiazine derivatives on a stochastic
      model of brain compression edema-swelling].
AB  - Search for pathogenically substantiated drugs to treat and prevent brain edema
      swelling (BES) is a topical problem of modern biology and medicine. It is
      possible to solve this challenging biomedical problem by using a method for
      devising a stochastic model of the tested process. The developed stochastic model
      of BES identifies the nerve tissue structural components involving in the anti
      edematous mechanism of action of phenothiazine derivatives under the conditions
      of 7-day brain compression. Analyzing the results of this model application
      revealed the major governing structures in the morphofunctional complexes under
      study. The investigations made on the stochastic model yielded a quantitative
      assessment of the impact of morphofunctional structural relationships under the
      influence of disturbing factors.

PMID- 9157372
TI  - [Lipid spectrum of rat liver and brain after administration of pyrazole].
AB  - The effect of pyrazole (360 mg/kg, intraperitoneally) on the levels of lipid
      fractions was studied in the rat liver and brain. There were no differences in
      hepatic lipid levels after administration of pyrazole alone and in combination
      with ethanol (20% solution, 1 g/ kg body weight, intragastrically). Pyrazole
      alone or in combination with alcohol elevates the concentrations of cholesterol,
      total phospholipids, phosphatidylethanolamine, and cerebrosides III, reduces the
      levels of sphingomyelin and cardiolipin.

PMID- 9157373
TI  - [Structural-functional changes in liver and brain in endotoxic shock
      (ultrastructural study)].
AB  - An additional clearance link forming the Kupffer's cell-hepatocyte microsystem
      that protects the body from endotoxemia was found in the early period of hepatic
      endotoxic shock. Sensory cortical neurons display dystrophic changes in the
      neurons of the sensory cortex and capillary exhibit hemodynamic disorders as
      plethora and enhanced permeability of the blood-brain barrier. In the intervening
      period of shock, there are first signs of block in the Kupffer's cell-hepatocyte
      system and drastically marked microcirculatory and dystrophic disorders. Lesions
      further progress in the nerve and glial cells, microvessels, and synapses of the
      sensory cortex. In late endotoxemia, there are cerebral and hepatic destructive
      changes that predispose to hepatocerebral insufficiency.

PMID- 9157374
TI  - [Reaction of cells of subcutaneous connective tissue to the activation and
      blockade of the peptidergic system].
AB  - Changes in the quantitative composition of subcutaneous connective tissue cells
      were examined after activation and blockade of the peripheral peptidergic system
      with capsaicin. The activating dose (5 mg/kg) of the agent was found to increase
      the quantity of mast cells in the subcutaneous connective tissue. Its toxic dose
      (200 mg/kg) elevated the histiocytic and fibroblastic index while the number of
      mast cells reduced. The same reaction was seen in surgically impaired tissue
      innervation. It is concluded that peptidergic capsaicin-sensitive neurons play a
      role in the development of neurogenic dystrophy and this process involves
      connective tissue cell elements.

PMID- 9157375
TI  - [Effectiveness of prostatylene in the prevention of decompression disease in an
      experiment].
AB  - Works done under elevated environmental pressures present a risk for
      decompression disease. The use of altitude chambers for its prevention and
      treatment is technically complex and expensive. The paper presents the results of
      studies into the effects of the new peptide regulator prostatylene isolated from
      the bovine prostate. Experiments were conducted on 132 albino noninbred male rats
      weighing 180-220 g. All the rats were divided into 10 groups by the dose (from
      0.5 to 5.0 mg/kg) and frequency of prostatylene administration (1-11 days). The
      agent was injected in a single intramuscular dose. Altitude exposure was made in
      a 75-liter chamber provided by a chemical absorbent container. Air temperatures
      were constant (19-21 degrees C) humidity was no higher than 75%. A compressor was
      used to pump as high as 0.7 MPa. The duration of compression, isopression, and
      decompression was 3 min, 1 hour, and 80 sec, respectively. The percentage of rat
      deaths and the interval from the termination of decompression to death were used
      as an index for the efficacy of prostatylene. The preset altitude exposure led to
      75% death in control rats. A single dose of prostatylene did not affect this
      index, but thrice preinjection of the agent showed as high as 25% animal death
      reductions. Its protective properties were shown when the agent was administered
      in a dose 1 mg/kg for 5 days. It is concluded that the prostate participates in
      the formation of nonspecific mechanisms of defense when the body is influenced by
      environmental factors and that prostatic peptides are able to prevent
      decompression disease in the experiment.

PMID- 9157376
TI  - [Primary osteoarthrosis: role of local immunologic responses, ways of
      correction].
AB  - Immunofluorescence was used to study the count of joint synovial membrane cells
      producing immunoglobulins of major classes (A, M, G) in 30 rabbits on a model of
      experimental arthrosis and the effects of rumalone, rumalone + indomethacin, and
      food deprivation. Clinically, the levels of immune responses in patients with
      primary osteoarthrosis were judged from the content of rumalone-sensitive serum
      antibodies. The development of experimental arthrosis was found to be followed by
      a substantial increase in the count of synovial membrane cells locally
      elaborating immunoglobulins chiefly G and M. With this, the use of
      pathogenetically substantiated therapy with chondroprotective agents produced a
      slight effect on the degree of local immune response impairments. Correction of
      the latter may be made with indomethacin and food deprivation in the experiment,
      as well as with indomethacin and microwave resonance therapy in the clinical
      setting.

PMID- 9157377
TI  - [Effect of calcium channel blockers on temperature in mice].
AB  - In the experiments on SHR mice, verapamil, nifedipine, cinnarizin, fendilin,
      diltiazem, and nimodipine were tested for their effects on changes in rectal
      temperatures after intraperitoneal and intracerebroventricular injections.
      Intraperitoneal nifedipine (2 and 10 mg/kg), fendilin (5 and 20 mg/kg), and
      cinnarizin (5 and 50 mg/kg) lowered rectal temperatures. The similar effects were
      shown by nimodipine (2.4 micrograms), diltiazem (100 micrograms), and verapamil
      (100 micrograms) after their intracerebroventricular injections. It is concluded
      that the hypothermal effect of calcium antagonists is based on their central and
      hemodynamic mechanisms.

PMID- 9157378
TI  - [Effect of cold stress on the contractile activity, carbohydrate and energy
      metabolism in the isolated rat heart].
AB  - Acute cold stress (-20 degrees C for 4 hours) in rats causes profound contractile
      changes in the heart isolated and perfused by the Langendorf method. This reduced
      contraction amplitudes and increased heart rates. The decreased contraction
      amplitudes was associated with inadequate ATP formation. While changing perfusion
      of post-stress isolated heart, myocardial rigidity slowed down, which seemed to
      be associated with activated glycolysis. There were no signs of cardiomyocytic
      lesion after cold stress. Reduced coronary flow is the only abnormal effect of
      acute cold stress under these conditions. High cardiac resistance to the damaging
      effect of cold is likely to be related to increased processes of glycolysis and
      glycogenolysis in the cardiomyocytes.

PMID- 9157379
TI  - [Dynamics of ultrastructural changes in guinea pig cardiomyocytes in experimental
      diphtheria intoxication].
AB  - Electron microscopy of the left and right ventricles from guinea pigs was made
      24, 72, and 120 hours after they were administered diphtheria toxin, 0.3 DLM/kg.
      The important pathogenetic mechanism responsible for dysfunction of the
      "diphtheritic heart" was found to be left and right ventricular cardiomyocytic
      lesion discordance developing in the mid-process, by causing serious intracardiac
      hemodynamic disorders. The lysosomal system influencing the ultrastructure of the
      two ventricles may exist in the heart. In diphtheritic intoxication,
      cardiomyocytic lysosomes exert mainly a damaging effect on their ultrastructure.

PMID- 9157380
TI  - [Disorders developing under combined exposure to ionizing radiation and stress].
AB  - The combined influence of gamma-radiation in a dose of 1 Gy and restriction
      stress was studied in experiments on 62 rats. The severity of gastric mucosal
      erosive and ulcerative lesions, the rate of lipid peroxidation, and hepatic
      homogenate heat generation were determined by microcalorimetry. The developing
      disorders were corrected by administering sodium succinate. Animal radiation
      resulted in modified stress-induced gastric mucosal lesions which appeared as
      increases in the total number of ulcerations. The use of sodium succinate was
      followed by less severity of erosive and ulcerative gastric mucosal lesions,
      lower levels of malonic dialdehyde, and decreased hepatic homogenate heat
      elaboration.

PMID- 9157381
TI  - [Effect of low-intensity laser irradiation as affected by maximum tolerable
      exercise].
AB  - The investigations on albino noninbred male rats showed that low-intensity laser
      radiation ("Uzor" semiconductor laser, wavelength 0.89 mu, 1500 Hz, exposure 8
      min) substantially increased physical work capacity during the maximum tolerable
      exercise. In addition, the plasma concentrations of thyroxine and malonic
      dialdehyde increased and the levels of lactic acid and triiodothyronine
      decreased.

PMID- 9157382
TI  - [Role of local fibrinolytic activity of the uterine horns in rats in the
      pathogenesis of formation of postoperative adhesions].
AB  - Experimental models were used to examine the impact of corrections of the uterine
      horns on the activity of tissue plasminogen activator (tPA). The application of
      sutures was shown to suppress the activity of tPA in the uterine horns to a
      greater extent than other surgical techniques. With this, the use of catgut
      caused the highest suppression of tPA activity and increases in the frequency and
      density of formation of postoperative adhesions. Depleted tPA reserves and its
      higher inhibitor levels were found to lead to depressed fibrinolysis, which is a
      pathogenetic factor for developing an adhesive process.

PMID- 9157383
TI  - [Features of uterine contractile function in intrauterine fetal death].
AB  - Experiments on 528 pregnant rats studied the specific features of uterine
      contractility in pre- (7.2%), postimplantation (5.69%), and intrauterine (1.14%)
      fetal deaths and in ablatio placentae (0.57%) which spontaneously occurred in
      this group of animals. By applying the multiparametric approach and the methods
      of the image recognition theory, the authors showed that despite its onset
      periods, fetal deaths resulted in reduced uterine contractility. It is concluded
      that the present study provides experimental evidence for the development of weak
      clinical uterine activity in fetal death in different periods of pregnancy. At
      the same time, myometrial responses to oxytocin decrease.

PMID- 9157384
TI  - [Pathogenesis of fibromyalgia].

PMID- 9157385
TI  - [Regulation of expression of the surface structure of the lymphocyte membrane by
      purine compounds in health and in disease].

PMID- 9157386
TI  - [Effect of various perfusion temperature regimens in heart surgery with
      extracorporeal circulation on glutathione levels and activity of enzymes of
      glutathione metabolism in erythrocytes].
AB  - The level of glutathione and the activity of its exchange enzymes (glutathione
      reductase, glutathione-S-transferase, glutathione peroxidase), the content of
      malonic dialdehyde were studied in the red blood levels of 70 patients operated
      on under hypothermal perfusion for correction of acquired cardiac diseases. The
      plasma concentrations of myoglobin were also measured. There was a relationship
      of the time course of changes in the parameters in question to the depth of the
      body's cooling during surgical interventions. Shallow hypothermia (30-34 degrees
      C) caused a compensatory increase in the activity of glutathione peroxidase (by
      more than 30%) and in the concentration of glutathione (by more than 60%) at the
      cooling stage. Moderate hypothermia (26-29 degrees C) produced no impact on the
      level of glutathione and the activity of its exchange enzymes while deeper
      hypothermia (25 degrees C or below) induced decreases in the levels of
      glutathione (by more than 30 degrees C) and suppressed the activity of all the
      tested enzymes of its exchange. At the same time there are elevated
      concentrations of malonic dialdehyde at the warming-up stage and during early
      postperfusion. Myoglobin washing into plasma occurs under all temperature
      conditions of perfusion at the warming-up stages and in the early postperfusion
      period, but it is most profound in deeper hypothermia, which is caused by the
      toxic effect of oxygen whose plasma solubility increases with lowered
      temperatures.

PMID- 9157387
TI  - Pediatrician's responsibility for infant nutrition. American Academy of
      Pediatrics. Committee on Practice and Ambulatory Medicine.

PMID- 9157388
TI  - Antenatal phenobarbital therapy and neonatal income.

PMID- 9157389
TI  - Fragile X: treatment of hyperactivity.

PMID- 9157390
TI  - Early deaths in Chicago and New England.

PMID- 9157391
TI  - Obesity and penicillin dosage.

PMID- 9157392
TI  - Pulmonary alveolar proteinosis.

PMID- 9157393
TI  - Pediatric emergency medicine fellowship programs.

PMID- 9157394
TI  - [Disappearance of shame and puberty in girls].
AB  - The sense of shame seems to vanish for more than a decade now, manifested e.g. by
      an increasing tolerance toward the naked female body. However, it is supposed
      that shame has still its significance especially during female puberty.
      Psychological considerations referring to shame and to the puberty of girls are
      reported and the significance of feeling ashamed in this salient segment of
      female development is delineated. Finally a concept is proposed within which the
      feeling of shame is understood as a possibility to create accordance between the
      positive aspects of being ashamed and the tendency of going beyond the borders of
      shame usually guaranteed by social rules.

PMID- 9157395
TI  - [Sleep behavior in the first 3 years of life].
AB  - A review of the literature on sleeping "disorders" in infants and toddlers shows
      that sleep problems are very common. We report the results of a German
      multicenter epidemiological study on a birth cohort (N = 1314). The children had
      medical examinations at 4 weeks, 3 months, 6 months, 1 year, 18 months, 2 years
      and 3 years. Most of the information on the sleeping behavior was gathered by
      structured interview and questionnaires. This paper gives information on the
      prevalence and the persistence of sleep problems in one to three year old
      children in Germany. Statistical analysis of correlations between breastfeeding
      and sleep and the place of sleep are reported. The consequences of sleep problems
      on the family overall well-being are also examined.

PMID- 9157397
TI  - [Developmental trends in breast pathology].

PMID- 9157396
TI  - ["Enuresis diurna" is not a diagnosis--new results on classification,
      pathogenesis and therapy of functional urinary incontinence in childhood].
AB  - Newer research results have shown that the previous classification of enuresis
      into nocturnal, nocturnal and diurnal and diurnal forms is not sufficient. Day
      wetting constitutes a heterogeneous group of syndromes, which should be
      considered as functional urinary incontinences and which require differentiated
      diagnostics and therapies. General aspects of functional urinary incontinence are
      discussed, including: classification, epidemiology, symptomatology, especially
      the association with urinary tract infections, vesicoureteral reflux, obstipation
      and encopresis. The rate of psychiatric problems seems to be increased compared
      to children with nocturnal enuresis. Methodological problems of previous studies
      are discussed. General guidelines regarding diagnostics and therapy include the
      requirement of sonography, uroflowmetry with pelvic-floor-EMG, urinalysis and
      specific therapy-forms. The three most important syndromes are urge incontinence
      with urge symptoms, frequent micturition, holding manoeuvres due to a
      physiological instability of the detrusor and lower, mostly secondary psychiatric
      symptoms. Voiding postponement is a general refusal syndrome with a psychiatric
      etiology, characterized by a postponement of micturition and retention of urine.
      The detrusor-sphincter-dyscoordination has as the main symptom a paradox
      contraction instead of relaxation of the bladder sphincter during micturition. It
      is recommended hat the previous classification should be left in favour of more
      specific diagnoses to ensure specific, causally effective therapies.

PMID- 9157398
TI  - [Indications for and accuracy of biopsy diagnosis in head-neck surgery].

PMID- 9157399
TI  - [Biopsy examination in neurosurgical operations].

PMID- 9157400
TI  - [DNA cytometry in breast carcinoma. Review of method and value in assessing
      prognosis].
AB  - DNA flow cytometry (FCM) has become a routine method in breast cancer diagnosis
      for evaluation of ploidy and proliferation kinetics (cell cycle analysis). Image
      cytometry is less practicable and provides less information than flow cytometry.
      An optimized technique with a low coefficient of variation is required for
      optimal results in flow cytometry. The S-phase fraction and the proliferation
      index (sum of S-phase fraction and G2M fraction) provide prognostic and
      therapeutically relevant information. A profound knowledge of the technique and
      its limitations is indispensable for the interpretation of FCM results. It
      remains to be established whether immunohistological evaluation of cell
      proliferation has the same prognostic value. Future developments are to be
      expected from multiparametric analysis and the improvement of mathematical
      analysis of FCM measurements.

PMID- 9157401
TI  - [Mastitis. Classification, histopathology and clinical aspects].
AB  - The frequency of biopsies with different types of mastitis among all patients
      with benign breast diseases in twenty years was 3%. About 2/3 of the patients
      were younger than 50 years, the average age was 46.7 years. Comparing the
      frequency of the different types of mastitis the puerperal mastitis is very rare
      in contrast to the increasing non-puerperal and granulomatous inflammatory breast
      lesions. The diagnosis "granulomatous mastitis" is one of exclusion. Both non
      infectious and infectious causes must be considered. The origin of the
      granulomatous mastitis often is unknown, but it is supposed to be an autoimmune
      localized response due to the retained and extravasated fat and protein rich
      secretions in the ducts in cases of hyperprolactinemia (drug induced or by
      microprolactinomas) or hormonal imbalances characterized by epitheloid cell
      granulomas with giant cells microabscesses around lipid drops, but without
      necroses. An idiopathic type of granulomatous mastitis concerns young women in
      relationship to parturition with a similar histological pattern predominantly of
      the lobules. Special types of mastitis are the B-lymphocytic autoimmune mastitis
      associated with a longstanding insulin-dependent diabetes mellitus type I, the
      sarcoidosis, panniculitis and the rare but very different infectious diseases
      with breast involvement. Particularly in cases without features of secretory
      activity a carefully bacterioscopic and microbiologic work-up of fresh material
      from the surgical specimens is necessary for a final diagnostic report.

PMID- 9157402
TI  - [Ductal hyperplasia and ductal carcinoma in situ. Definition--classification-
      differential diagnosis].
AB  - This review emphasizes the pathology of premalignant ductal breast diseases and
      its practical relevance to the patients management. The histological criteria for
      recognizing Ductal Hyperplasia (DH) are now well established. These include an
      intraluminal heterogeneous proliferation of glandular cells positive for keratins
      8/18/19 and epithelial cells with expression of keratins 5/6/14. As a
      hyperplastic process the epithelial cells disclose an haphazard irregular growth
      with slit like irregular lumina (fenestrated growth pattern). The florid DH
      indicates a slight subsequent increased risk for cancer development. Our
      knowledge of the nature of noninvasive ductal neoplasia continues to evolve.
      Recent molecular genetic and immunohistochemical efforts have disclosed that
      atypical ductal hyperplasia (ADH) constituted a clonal neoplastic proliferation
      of an epithelial cell. Histological hallmarks of ADH are their cytologic features
      of uniformity and monotony of proliferation of cells and its micropapillary,
      cibriform or solid growth pattern. So from histology ADH simulates the highly
      differentiated DCIS, but can be distinguished from the latter quantitatively by
      the aggregate cross sectional diameter or the number of ducts that are completely
      involved by the atypical proliferation. ADH indicates a few fold subsequent
      increased risk for developing carcinoma. So this lesion requires a close follow
      up with 3 to 4 examinations per year and annual mammograms. Ductal carcinoma in
      situ (DCIS) consists of cytologically malignant cells in the parenchyma that have
      not invaded into the stroma. Recent studies have shown that DCIS is a
      heterogeneous group of tumors. Attempts have been made to classify it into
      histologic patterns, nuclear grades, tumors with or without comedo-necroses etc.
      We can draw the conclusion from several studies that the most important
      histologic feature is the nuclear grade. Holland et al. have suggested a very
      useful classification scheme that includes nuclear grade and histological
      features. The modifiers of treatment are as follows: 1. nuclear grade or
      differentiation of the DCIS 2. extension of the lesion 3. excision with clear
      margins So efforts to classify DCIS underscore the central role of pathology in
      determining the grade of the DCIS, its size and the adequacy of the surgical
      excision in terms of free margins. All three parameters are included in a score
      system of the Van Nuys Prognostic Index.

PMID- 9157403
TI  - [Subtyping and prognostic assessment of invasive lobular breast carcinoma].
AB  - Invasive lobular carcinoma (ILC) is recognized in its classical form and as
      variants with tubulo-lobular, solid, pleomorphic, alveolar or signet ring cell
      differentiation. The most common classical form differs from invasive ductal
      carcinoma (IDC) by its slower tumor proliferation and less common axillary
      metastases. When compared stage by stage, long term prognosis is similar to IDC,
      however. Prognostic subtyping of ILC can be achieved by the recognition of
      variant forms and mitotic counting. The combination of these factors may be used
      for tumor grading (5-year survival 100% with grade 1 vs. 82% with grade 2, and
      57% with grade 3, n = 241). The detailed histopathologic diagnosis therefore
      permits prognostic assessment also in ILC.

PMID- 9157404
TI  - [Breast carcinoma in the man. Current results from the viewpoint of clinic and
      pathology].
AB  - Breast cancer is the most frequent malignant tumor in women, whereas it is rare
      in men. In our own case series the ratio is 175:1. The present paper deals with
      an evaluation of clinical and morphological findings from a series of 54 de novo
      male breast cancers observed in our institution from 1978 to 1996 and a
      comparative discussion of 528 female breast cancers from the same geographic
      area. We should like to focus on the following observations: At the time of
      histopathological diagnosis, male patients with breast cancer were on average 67
      (34-87) years old and thus 5 years older than women. Below the age of 40, breast
      cancer is very rare in men. The lag time between first symptoms and surgery was
      on average 42 weeks, i.e. twice as long as in women. In the vast majority of
      cases palpation of a retromamillary nodule was the leading diagnostic symptom.
      Mamillary secretion appeared to be an early symptom with favorable relation to
      prognosis by tumor size whereas diffuse breast swelling was an unfavorable late
      symptom. Bilateral carcinoma and double cancer (breast and prostatic cancer) was
      observed in one case each. Three patients (3/51 = 6%) had a positive family
      history (breast cancer in 1st and 2nd degree relatives). The average invasive
      tumor size was nearly identical with 23 mm (s11.02) in men and 25 mm (s13.48) in
      women. Men presented more frequently with regional lymph node metastases (53%
      versus 45%), which tended to develop earlier. pT4 cancers were twice as frequent
      in men compared to women. In situ cancers were found in 2% (1/54) in men and 4%
      in women. Similar to females, male breast cancers are predominantly of ductal
      histological type (NOS-cancers), classical lobular carcinoma with LCIS-components
      were not observed; special forms (tubular, papillary, mucinous) are slightly more
      common in men. When reviewing our series, need for revision of the origin of
      tumor was not found in any of the cases. Metastases of prostatic cancer were
      never misinterpreted as primary breast cancer. In case of isolated NSE-reaction,
      cancers with carinoid differentiation pattern are to be found in nearly every
      second tumor. However, when multiple markers were used (chromogranin A or
      synaptophysin) only 10% displayed such pattern, which corresponded to a positive
      hormone receptor status in each case. Quantitative (enzyme immunoassay) and
      semiquantitative (immunohistochemistry) analysis of steroid hormone receptor
      status was positive in 86% of 35 cases in men and in 75% in women. In contrast to
      female breast cancer, hormone status proved to be independent of age in males.
      The average levels of estrogen and progesterone were higher in men. Overlapping
      results were found only when cases were compared with postmenopausal women. The
      Nottingham prognostic index, a product of primary tumor size, axillary lymph node
      status and grading allows an approximative estimate of the course of the disease;
      its predictive value is higher than that of isolated tumor markers.

PMID- 9157405
TI  - [Standardized pathologic examination of breast excision specimen. Relevance
      within an interdisciplinary practice protocol for quality management of breast
      saving therapy].
AB  - The long-term disease free survival in patients treated by breast conserving
      therapy is similar to that of patients treated by mastectomy. In breast
      conserving therapy there is a significant risk of local recurrence. Although
      local recurrence does not appear to effect survival, there is certainly
      associated morbidity and attendant emotional trauma. Microscopic evaluation of
      the margins of lumpectomy specimens is the only way to define the extent of the
      tumour and the adequacy of resection. We intended to check the influence of
      standardized handling instructions for pathological examination on the results of
      histological margin assessment. These instructions are part of a practice
      protocol for all branches involved in BCT. We compared the results of our
      standardized margin investigation of 100 cases with the analysis of the margin
      status of 100 Lumpectomy specimens each from two other periods of time with
      different handling. Before 1989 only margins where tumor tissue was suspected
      when checked with the naked eye were investigated microscopically. From 1990 till
      1991, margins were evaluated more intensively, but the evaluations were not
      standardized and did not consider the orientation of the ductal system, which was
      the base of examination after 1992. In 28% of cases, tumour tissue was found upon
      the investigation under the microscope, in the margins of lumpectomies where the
      margins looked clear to the naked eye. In the other periods tumour could be found
      in the margins in only 2% respectively 12%. Our results verify a strong influence
      of our practice protocol on the results of the examination of LE specimens: At
      first there is a higher sensitivity for tumor bearing margins compared with
      random sampling of margin tissue. Moreover, based on the consideration of the
      ductal orientation our protocol offers a better chance to detect in situ
      components of tumor in the margins. Finally with our method we are able to design
      exactly the tumor bearing margin and therefore we could take part in quality
      assurance of BCT.

PMID- 9157406
TI  - [When are recommended breast biopsies carried out, and what information does the
      physician responsible for mammography receive? Experiences with 317 breast biopsy
      in a regional quality assurance project for screening mammography].
AB  - In a regional quality assurance project for screening mammography (German
      Mammography Study), 27,335 women were screened in 40 participating, office-based
      mammography units from 1990-1992. Screening led to 317 biopsies with a positive
      predictive value of 0.33. All biopsy documentation available to the mammography
      physicians was analysed with a view towards biopsy interval and completeness of
      information fed back to the Mx physicians. Biopsy recommendations were acted upon
      in 29% of cases within 2 weeks. With the exception of the dignity Mx physicians
      were incompletely informed about biopsy results. The surgical procedure was known
      in the doctors' offices in 62% of the cases. Specimen radiographies were not done
      regularly. A pathology report was available overall in 42 of 106 malignant cases,
      respectively. With the exception of the histological diagnosis itself, no
      variable mentioned in the reports was documented completely. Only one third of
      the physicians received such reports routinely. Fail-safe information are
      requested by Mx physicians and can help them to better target biopsy
      recommendations. A (regional) quality assurance center should be made responsible
      to analyse the flow of information in mammography screening, to fill in gaps and
      to speed up professional cooperation.

PMID- 9157407
TI  - [Lupus vulgaris as the etiology of tuberculous mastitis].
AB  - We report the rare case of granulomatous tuberculous mastitis based on lupus
      vulgaris in a 73-year-old female patient. The most important diagnostic procedure
      was the detection of mycobacterial DNA-sequences in paraffin-embedded tissues
      using the polymerase-chain-reaction (PCR). A combined antituberculous therapy
      lead to complete remission within 14 months after the diagnosis was established.
      The incidence of tuberculous mastitis among surgically treated lesions of the
      breast is less than 0.025 percent. Because of the frequent localisation of this
      disease in the upper outer quadrant of the breast and suspicious findings in
      mammography, tuberculous mastitis is one, even if rare, differential diagnosis
      for breast cancer.

PMID- 9157408
TI  - [Guidelines for pathology--supplement to European guidelines for quality
      assurance in mammography screening. Report by the Pathology Working Group of the
      European Community].

PMID- 9157409
TI  - [General aspects for biopsy examination].

PMID- 9157410
TI  - [Problem cases in routine diagnosis by the pathologist--indications and accuracy
      of rapid section diagnosis. Uropathology].

PMID- 9157411
TI  - [Biopsy examination of lung diseases].

PMID- 9157412
TI  - [Intraoperative diagnostic frozen section of the thyroid gland].

PMID- 9157413
TI  - [Hyaluronic acid: biological role, structure, synthesis, isolation, purification,
      and application (review)].
AB  - The methods for isolation and purification of hyaluronic acid are summarized. The
      structural properties of this mucopolysaccharide are discussed, and hyaluronic
      acid-hydrolyzing enzymes are characterized. Data on the biological role,
      properties, and content of hyaluronic acid in tissues are reviewed. The
      possibilities of the application of hyaluronic acid in medicine, cosmetology,
      veterinary science, and hygiene are discussed.

PMID- 9157414
TI  - [Equilibrium and kinetic parameters of interaction between peroxidase conjugates
      of strophanthin and anti-peroxidase antibodies].
AB  - Interactions of three horseradish peroxidase (HRP)-strophanthin conjugates
      containing one, two, or three glycoside molecules (HRP-Str1, 2, or 3,
      respectively) with polyclonal anti-HRP antibodies were studied by homogeneous
      enzyme immunoassay. The total peroxidase activity of free conjugates and their
      immune complexes was estimated from the oxidation of o-phenylenediamine. The
      dissociation constants of the immune complexes and the rate constants of their
      dissociation and formation were determined. The equilibrium and kinetic
      parameters were determined for the interactions of the HRP-Str2 immune complex
      with anti-strophanthin and anti-HRP antibodies. The determined equilibrium and
      kinetic parameters of the HRP-Str interactions with anti-HRP antibodies depended
      on the molecular weights, sizes, and structures of the antigens studied.

PMID- 9157415
TI  - [Interaction between globular proteins and water-soluble carbodiimides].
AB  - Interactions of a number of globular proteins with 1-ethyl-3-(3
      dimethylaminopropyl) carbodiimide were studied. Under conditions of carbodiimide
      excess at a protein concentration lower than 88.5 x 10(-5) mol/l, the
      crosslinking reaction was found to proceed exclusively by an intramolecular
      mechanism. This resulted in conformational changes in the protein secondary
      structure and decreased its biological activity. At higher protein
      concentrations, the reaction of intramolecular crosslinking was always the first
      to proceed, and only then intramolecularly crosslinked proteins interacted. The
      reaction of intermolecular crosslinking was not followed by a further change in
      the protein conformation and activity.

PMID- 9157416
TI  - [Structural transitions of serum proteins in solutions during high- and low
      temperature dehydration].
AB  - Infrared and ultraviolet spectroscopy, potentiometric titration, and
      refractometry, as well as analysis of lysine, tryptophan, and tyrosine
      availability, and enzymic hydrolysis were used to establish that high-temperature
      and low-temperature dehydration of solutions of serum protein is accompanied by a
      rearrangement of its molecular structure, resulting in changes in the number of
      polar radicals and hydrophobic bonds, intermolecular and intramolecular
      interactions, and the formation of a new stable conformation. Comparison of the
      two methods of dehydration showed that cryoconcentration resulted in a greater
      accessibility of the protein molecule to chemical agents and proteolytic enzymes,
      whereas heating had an opposite effect.

PMID- 9157417
TI  - [Lung diseases in Germany].

PMID- 9157418
TI  - [Bronchial asthma].

PMID- 9157419
TI  - [Chronic bronchitis].

PMID- 9157420
TI  - [Pulmonary emphysema].

PMID- 9157421
TI  - [Mucoviscidosis/cystic fibrosis (CF)].

PMID- 9157422
TI  - [Pneumonia].

PMID- 9157423
TI  - [Tuberculosis].

PMID- 9157424
TI  - [Bronchial carcinoma (lung cancer)].

PMID- 9157425
TI  - [Environmental and occupational diseases].

PMID- 9157426
TI  - [Sleep related respiratory disorders].

PMID- 9157427
TI  - [Interstitial lung diseases].

PMID- 9157428
TI  - [ARDS (adult respiratory distress syndrome)].

PMID- 9157429
TI  - [Pneumology in Germany].

PMID- 9157430
TI  - [Current therapy of pulmonary fibrosis. Proceedings of a conference. 13-14
      October 1995].

PMID- 9157431
TI  - [Did Frederic Chopin actually suffer from tuberculsis?].

PMID- 9157432
TI  - [Modern methods for detecting exocrine pancreas insufficiency in mucoviscidosis].

PMID- 9157433
TI  - [What is "modern physical therapy"?].

PMID- 9157434
TI  - [Psychosocial aspects of mucoviscidosis/cystic fibrosis in adulthood].

PMID- 9157435
TI  - [Quality of life and improving the quality of life of mucoviscidosis patients].

PMID- 9157436
TI  - [The path from the pediatrician to the internist].

PMID- 9157437
TI  - [Antibiotic treatment strategies in cystic fibrosis].

PMID- 9157438
TI  - [New perspectives of antioxidant therapy with thiols: nacystelyn].

PMID- 9157440
TI  - [Amiloride inhalation].

PMID- 9157439
TI  - [Proteinase/antiproteinase balance in patients with cystic fibrosis].

PMID- 9157441
TI  - [Comparative mucolytic drug therapy].

PMID- 9157442
TI  - [Lung transplantation].

PMID- 9157443
TI  - [Gene therapy: development of adenovirus vectors].

PMID- 9157444
TI  - [Gene therapy research in cystic fibrosis--lessons from early clinical studies].

PMID- 9157445
TI  - [Functional success follow-up in mucoviscidosis gene therapy].

PMID- 9157446
TI  - [Podium discussion of the gene therapy and heterozygote screening topic].

PMID- 9157447
TI  - [Partial liquid ventilation with perflubron in premature infants with severe
      respiratory distress syndrome].

PMID- 9157448
TI  - [Quality of life in patients with chronic obstructive lung diseases: psychometric
      criteria of the German version of the Sickness Impact Profile and initial results
      of its application].
AB  - BACKGROUND: Quality of life has become an important criterion for assessing
      disease impact and treatment outcome. The Sickness Impact Profile (SIP) is an
      internationally widely used generic instrument for the measurement of health
      related quality of life. Furthermore, it has been frequently employed for
      research in patients suffering from airway diseases. Therefore, we developed a
      German version of the SIP and investigated its psychometric properties in
      patients with chronic obstructive lung disease (COPD). PATIENTS AND METHODS:
      After translation of the SIP into German, the results of a pilot study suggested
      several changes. Some items had to be reformulated and the SIP subscales
      "Emotional and affective behavior", "Alertness" and "Body care and movement" had
      to be discarded because of insufficient psychometric properties. The reliability,
      validity and sensitivity of the resulting German SIP version were investigated in
      a sample of 58 O2-dependent patients with COPD. RESULTS: Internal consistency
      (Cronbach Alpha) was 0.93 for the entire instrument, while it was 0.85 for the
      SIP psycho-social scale and 0.89 for the SIP physical scale. The internal
      consistency ranged from 0.55 to 0.86 for the subscales of the German SIP version.
      The nutrition subscale was discarded because it showed an insufficient internal
      consistency (0.40). Indices of respiratory function (FEV1, FVC, Pa, O2, Sa, O2)
      and severity of dyspnea as assessed by the Baseline Dyspnea Index (BDI) were
      associated with the total SIP, psycho-social and physical score reaching from r =
      -0.19 to r = -0.48. Patients who improved after introduction of liquid oxygen
      therapy (LOX) showed a better total SIP score (p = 0.023) and less impairment in
      the SIP physical scale (p = 0.009). In order to evaluate the prognostic validity
      of the German SIP, a discriminance analysis between those patients who were alive
      14 months later and those who had died of their illness was performed. A single
      discriminant function with an Eigenvalue of 0.59 (canonical correlation r = 0.61;
      CU2 = 21.213; df = 3; p < 0.001) was found. By means of the FVC, the severity of
      dyspnea (BDI), the SIP total score and the FEV1 85% of the survivors and 91 % of
      the fatalities could be predicted correctly. CONCLUSIONS: The present results
      demonstrate sufficient psychometric properties of the German SIP version for the
      use in patients with COPD and hypoxemia. However, the internal consistencies of
      the subscales "Work" and "Leisure pastimes and recreation" remain to be improved.
      Furthermore, the results of factor and cluster analyses suggest some changes in
      the internal structure of the German SIP.

PMID- 9157449
TI  - [Diagnosis, therapy and prevention of lung diseases: how do we know what is
      effective?].

PMID- 9157450
TI  - [Psychosocial aspects of chronic respiratory tract diseases (COPD): relevance and
      consequences for pulmonary rehabilitation].
AB  - As a part of the Davoser-Reha-Study, the significance of psychosocial aspects on
      the course of chronic pulmonary disease has been investigated on 414 patients
      (mean age = 47.1 years) with COPD (mean duration = 16 years) and a high
      percentage of multimorbidity (75%). Of special interest was the question, what
      kind of impact coping strategies do have on certain aspects of quality of life,
      in the sense of outcome criterias of the medical rehabilitation. Also it is not
      possible for the moment to draw final conclusions, because the knowledge about
      coping strategies and their adaptability is still very limited, the current study
      indicates, that some coping strategies are more supportive for adaptation than
      others. Positive for adaptation are strategies, which can be described as active
      exposition with the disease (fighting spirit, information seeking and active
      problem solving). Depressive coping strategies and the tendency to deny the
      disease seem to have a negative effect. All in all the results verify the strong
      necessity of taking psychosocial aspects into account for the complete treatment
      of chronically ill patients with COPD.

PMID- 9157452
TI  - [Cell types of respiratory epithelium: morphology, molecular biology and clinical
      significance].
AB  - The epithelium of the human lower airways is composed of several different cell
      types. In the proximal parts of the lower airways, the basal cell, the goblet
      cell, and the ciliated cell are the principal cell types. In the distal airways,
      the Clara cell and the ciliated cell are present. Serous and mucous cells are the
      secretory cell types of the glands which are found in the wall of the large
      airways. In the last few years, several cell- and molecular-biological
      characteristics of these cell types have been investigated and their importance
      to physiological and pathological processes has been clarified. The products of
      secretory cell types are essential for the mucociliary clearance and thus play an
      important part in defense. In many diseases, such as asthma or cystic fibrosis,
      the structure and function of these cells are altered in a characteristic way.
      Another defence mechanism is represented by the ciliated cells. Their function
      can be impaired by inborn or acquired diseases. Knowledge about cell
      differentiation and cell proliferation is important to understand both the
      physiological regeneration as well as pathological conditions, such as wound
      repair or neoplasms. Further, the development of gene-therapeutical approaches
      depends on the investigation of the molecular biology of the airway cells. It is
      the aim of this article to describe the morphology of the relevant cell types and
      molecular biological aspects of their function.

PMID- 9157451
TI  - [Physical therapy in patients with COPD and tracheobronchial instability-
      comparison of 2 oscillating PEP systems (RC-Cornet, VRP1 Desitin). Results of a
      randommized prospective study of 90 patients].
AB  - In a randomized prospective study in 90 patients with COAD and tracheo-bronchial
      instability 3 groups were formed. Group 1: Therapy as group 3+ Physiotherapy with
      VRP1 Desitin, Group 2: Therapy as group 3+ Physiotherapy with RC-Cornet, Group 3:
      CONTROL GROUP: daily 40 mg prednisolon i.v., 2 x theophylline i.v. in relation to
      serum levels and 3 x inhalation of beta 2+ parasympathicolytic with a compressor
      inhaler. Therapy group 1 and 2 received the same drug and inhalation therapy as
      the controls. Controls of lung function before and after physiotherapy and visual
      analog scales for dyspnoea, cough, sputum and acceptance of the physiotherapy
      were performed at days 1, 4 and 7. With RC-Cornet the residual volume decreases
      statistically significant in comparison to VRP1 Desitin. Hyperventilation is also
      statistically significant smaller in RC-Cornet compared to VRP1 Desitin. The
      subjective improvement of sputum, dyspnoea and acceptance of the method of
      physiotherapy was statistically significant better for RC-Cornet. Regarding cough
      the significance was just failed by p < 0.055. RC-Cornet is a comfortable,
      effective, small accepted tool for the long term physiotherapy of patients with
      COAD and tracheobronchial instability.

PMID- 9157453
TI  - [Oxidant-antioxidant imbalance in the experimental interstitial lung disease
      induced in sheep by visna-maedi virus].

PMID- 9157454
TI  - [German Society of Pneumology: Recommendations for diagnosis of community
      acquired pneumonia. "Diagnosis of Community-Acquired Pneumonia" Working Group].

PMID- 9157455
TI  - [Value of polymerase chain reaction (PCR) in diagnosis of tuberculosis and
      mycobacterium infections caused by ubiquitous mycobacteria].
AB  - The rise in both incidence and the number of multi-drug-resistant strains has
      made tuberculosis an alarming health problem even in some developed countries.
      Moreover, due to the HIV pandemic an increase in mycobacterial diseases caused by
      ubiquitous mycobacteria has been observed. The microbiological standard
      procedures are critical diagnostic tools, and a more rapid detection of
      mycobacteria by new laboratory techniques would be helpful. We investigated the
      role of the polymerase chain reaction (PCR) in the detection of M. tuberculosis
      complex and of ubiquitous mycobacteria. 580 clinical specimens obtained from 525
      patients were examined. The majority of sampled material was bronchoalveolar
      lavage fluid. Based on cultural identification of mycobacteria, the incidence of
      tuberculosis in our patients was 3.4%. For detection of M. tuberculosis complex
      the insertion sequence IS 6110 was used. Relative to cultural identification,
      diagnostic specificity of PCR was 99.5%, and sensitivity was 66.7%, respectively.
      In 3.0% of the total patient group and in 8.8% of HIV-infected patients an
      infection by ubiquitous mycobacteria was found. Ubiquitous mycobacteria were
      detected using the hypervariable region of the 16S-rRNA-gene, and species
      identification was done by sequence analysis. For ubiquitous mycobacteria,
      sensitivity of PCR was 60.0% relative to cultural identification and 62.5%
      relative to a proven disease. PCR is a useful method in the rapid diagnosis of
      pulmonary tuberculosis with excellent specificity but lack of sensitivity.

PMID- 9157456
TI  - [Complicated community-acquired pneumonias do not need invasive bronchoscopic
      pathogen diagnosis in routine management].

PMID- 9157457
TI  - [Bronchoalveolar lavage in childhood: technical aspects and reference values].
AB  - (BAL) has been increasingly used in recent years also in children. In paediatric
      pulmonary diseases, however, interpretation has proved difficult in the absence
      of standard reference values for BAL in childhood. It is the purpose of the
      present publication to discuss the methodological aspects of BAL in childhood and
      to proviced criteria by means of standard reference values for the assessment of
      BAL in paediatric patients. In a group of 50 children aged 3 to 15 years with
      healthy lungs, who were subjected to BAL during an elective surgical
      intervention, we examined both cellular and non-cellular components of the BAL.
      Whereas the percentage of macrophages and lymphocytes in the total population did
      not differ significantly from the standard values in adults, the absolute and
      relative granulocyte count was found to be elevated in children under 8 years of
      age. The CD4/CD8 quotient of BAL was 0.7 on the average, and hence clearly below
      the standard reference values defined for adults. In the non-cellular components
      we found an increase in the level of all proteins from plasma, whereas locally
      produced proteins did not differ from the findings in healthy adults. The total
      phospholipid content of BAL was markedly enhanced in children below 8 years of
      age and decreased with increasing age. These differences between children and
      adults should be taken into account when interpreting pathological findings. They
      are the basis for better defining the ranking of BAL in paediatric pulmonary
      diseases.

PMID- 9157458
TI  - [Differential cytology of bronchoalveolar lavage fluid in healthy children in
      comparison with children colonized by lung-specific pathogens].
AB  - BAL is increasingly used in the assessment of pulmonary diseases, however, the
      role in children remains to be defined. Therefore bronchoalveolar lavage (BAL)
      was performed on 21 healthy children in order to enable quantification and
      characterization of the alveolar cell populations. Reference values for cellular
      constituents of BAL fluid using rigid bronchoscopes are lacking-even though in
      children still 90% of bronchoscopies are done by rigid instruments and BAL is
      performed using a catheter leading into the lower lobe. The children, 12 months
      to 14 years of age, were lavaged adjusted to body weight with three 1 ml/kg
      aliquots of normal saline. Recovery was 31 +/- 12%. Each aliquot was analysed
      separately. The number of total cell count per milliliter was 29.8 x 10(4) (range
      0.6-161 x 10(4). Percentages of different cell types of the third simple were
      (mean): macrophages 88.5, lymphocytes 6.4, neutrophils 4.8, eosinophils 0.1,
      basophils 0%. Significantly more neutrophils and less lymphocytes were found in
      the first as compared to the second and third sample. No age dependency was
      observed for either cell type. The comparison to cellularity of BAL-fluid with
      proven evidence of Adenovirus, Streptococcus pneumoniae, Moraxella catarrhalis
      and Haemophilus influenzae type B showed a marked influence of viral and
      bacterial germs. The study provides the first reference data on BAL differential
      cytology in healthy children using rigid bronchoscopy.

PMID- 9157459
TI  - [Combinatorial chemistry as a pool for new drugs].

PMID- 9157460
TI  - [Streptomycete genetics, basis for the production of new antibiotics].

PMID- 9157461
TI  - [Microdialysis for the determination of free drugs in tissues].

PMID- 9157462
TI  - [An advancement in drug research: rational drug design with combinatorial
      chemistry].

PMID- 9157463
TI  - [Robert Koch Institute: expert recommendations on procedures following
      occupational HIV exposure].

PMID- 9157464
TI  - [Prevention and responsible personal behavior remain effective weapons against
      AIDS].

PMID- 9157465
TI  - In vitro alkylating of alpha, beta-unsaturated amidoesters, diethyl
      pyridylmethylphosphonates and their cis-Pt(II)complexes.
AB  - The alkylating ability of alpha,beta-unsaturated amidoesters 1a-8d, diethyl
      pyridylmethylphosphonate esters and their cis-platinum(II) complexes has been
      investigated based on the test with 4-(4'-nitrobenzyl)pyridine (NBP) (Preussmann
      Test). Of the compounds tested for alkylating activity, only cis-platinum(II)
      phosphonate complexes were found to possess activity. The highest activity was
      found for CiS-[PtCl2(4-pmpe)2] where 4-pmpe is diethyl 4
      pyridylmethylphosphonate. The results show a correlation between alkylating
      activity in vitro and cytotoxic activity in vivo for platinum(II) complexes.

PMID- 9157466
TI  - [Sexual dysfunctions in men and women: significance of a dysfunctional family
      climate and sexual abuse].
AB  - The authors examined by questionnaire the prevalence and the possible
      relationship of childhood sexual abuse and dysfunctional family background to the
      later sexual dysfunctions in a nonclinical male and female student sample. Of the
      202 females, 44 (21.8%) reported a narrowly defined childhood sexual abuse, of
      the 301 men who completed the questionnaires 29 (9.6%) reported any kind of a
      sexually abusive experience, and 17 (5.6%) were victims of a marked childhood
      sexual victimization. 66 (32.6%) females and 79 (26%) males reported an adverse
      family background. Long-lasting adverse familial relationship to attachment
      figures were significant to later sexual dysfunctions in both sexes. Women, who
      reported repeated childhood sexual abuse, reported significantly more frequently
      sexual desire disorder and orgasm disorder. However, males who experienced-in
      most cases single-childhood sexual abuse, showed not more frequently sexual
      dysfunctions than nonvictims.

PMID- 9157467
TI  - [Countertransference in schizoid disorders].
AB  - Twelve experienced psychoanalysts diagnosed during a depth-psychological
      examination of 604 patients, coming from two different outpatient institutions,
      distinct clinical schizoid personality traits of 65 patients (10.7%). A further
      analysis researched the contribution to patient and therapist bindings and
      influences on the diagnosis. With the aid of a step by step regressions analysis
      including "solid" patient and therapist data as well as countertransference
      reactions of the investigator, we were able to establish an accurate diagnostical
      model, which enables a correct assignment with the probability of 90%. The most
      important diagnostic criterion proved to be the countertransference of the
      investigators. This demonstrates that affective processes from the therapist side
      should be assessed as a potent criterion that distinctively increases the
      validity of the diagnosis.

PMID- 9157468
TI  - [The ideal image and sex role norms in the Giessen Test].
AB  - This study was intended to test the assumption whether the ideal-image measure
      within the Giessen-Test reflects the specific personality as hypothesized by
      psychoanalytic theory or a general norm-orientation. To test this assumptions the
      items of the Giessen-Test were transformed an submitted to random samples of in-
      and out-patients. The results clearly indicate that the ideal-image as measured
      by the Giessen-Test is a general norm-orientation and consists of the dimensions
      "social-acknowledgement" and "capability of binding". Within the second dimension
      there seems to be a gender difference. Additional analysis of variance and
      Cronbachs alpha indicate that differences between in- and out-patients are the
      result of a possible "curative effect".

PMID- 9157469
TI  - [Category distribution and prognostic significance of operationalized
      psychodynamic diagnosis. Initial experiences with "OPD-1" in inpatient
      psychotherapy].
AB  - The paper describes the application of the system of "operationalized
      psychodynamic diagnosis" (OPD) which was developed in a multicentric effort
      during the recent years. The system is used for the classification of videotape
      recorded interviews with 30 patients prior to inpatient psychotherapy. The
      classification system allows the diagnostic assessment of the patients' illness
      behaviour, their interpersonal relationships, their conflicts, psychic structure
      and their symptoms. The aim of the study was a description of the patient group
      as well as a test of the relationship between diagnostic features and treatment
      outcome following several months of inpatient group psychotherapy. The study
      confirms the practicability of the OPD-system and shows that the description of
      the patient group seems to be plausible and valid. Single diagnostic categories
      seem to be useful for the prognosis of treatment outcome, especially structural
      features, but also characteristics of the patients' illness behaviour and their
      sensitivity for conflicts.

PMID- 9157470
TI  - [Quality of life and daily coping of chronic schizophrenic patients. Results of a
      qualitative pilot study].
AB  - The results of this qualitative exploratory study show that chronic
      schizophrenics partly cope successfully with the multivarious demands of everyday
      life, including the consequences of their illness. They mostly realize a
      relatively high level of quality of life. There is a distinct connection between
      the concrete institutional-therapeutic setting conditions and the multiplicity of
      participation in social life or the available ways of coping. We identified
      favourable and unfavourable coping modes as well as starting points for
      therapeutic interventions. A qualitative analysis of the individual case seems to
      be absolutely required, in order to estimate their efficiency.

PMID- 9157471
TI  - [Malignant lymphoma. Pathology, diagnosis, therapy].
AB  - Malignant lymphomas can be subdivided into Hodgkin's disease and low- or high
      grade non-Hodgkin's lymphoma (NHL). The principal therapeutic options are
      polychemotherapy and radiotherapy. Besides the histological classification,
      staging of the disease with particular regard to risk factors is an essential
      prerequisite for the therapeutic decision. Diagnostic imaging modalities such as
      computer tomography, magnetic resonance imaging, and ultrasonography have
      improved the accuracy of clinical staging such that invasive pathological staging
      is only necessary in exceptional cases. A novel therapeutic approach is high-dose
      chemotherapy with autologous haematopoietic stem-cell support. This treatment
      improves the survival of patients with relapsed high-grade NHL. The place of high
      dose therapy as the primary therapeutic option in malignant lymphoma is now being
      assessed in prospective studies following encouraging results from single-centre
      studies, including those involving the treatment of low-grade lymphoma. The
      effects of antibodies directed against lymphatic cells are currently being
      examined in experimental treatments. An assessment of the viability and rate of
      proliferation of lymphoma tissue on completion of therapy using sensitive
      radiological and nuclear medical methods is an important aim for the future.

PMID- 9157472
TI  - [Malignant lymphoma. Diagnosis and after-care in adults with special reference to
      cross-sectional imaging].
AB  - Radiological staging continues to remain the basis of a critical therapy of
      malignant lymphoma. As staging system, the Ann Arbor classification with some
      added modification is used. Up to now, CT is the imaging study of choice for
      staging and follow-up of cases of lymphoma. In future however, due to the
      advantages of the MRI, parts of the staging will be performed by MRI only.
      Imaging studies provide accurate measurement of extent of nodal disease. The
      detection of extra-nodal disease depends on the growth pattern and on the
      location. Focal lesions of sufficient size can be readily detected, diffuse
      infiltration is often missed. Computed tomography precisely reflects pathologic
      changes of lung involvement, but the findings are not specific. One weakness of
      the imaging studies is the low detection rate of splenic and hepatic involvement.
      Staging of gastrointestinal lymphoma has been improved by "hydro-CT" or "Hydro
      MRI".

PMID- 9157473
TI  - [Ultrasound criteria for staging and follow-up of malignant lymphoma].
AB  - Ultrasonography is an integral part of the radiological imaging of malignant
      lymphomas for staging, therapy planning, monitoring, follow-up, post-therapeutic
      care, and detection of recurrences, as well as the diagnostic differentiation of
      benign lesions and metastasis of solid tumors. None of the imaging methods,
      including sonography, however, can safely determine the stage (UICC certainty
      level C4) in agreement with the pathohistological examination. Also considering
      the clinical appearance the sonographic criteria in the synoptic evaluation will
      nevertheless provide important indications for diagnosis and therapy planning.
      Not only changes in size and shape, but also the echogenicity (gray-scale
      histogram) and vascularization (color Doppler) of nodal and extranodal processes
      are decisive criteria for estimating the therapeutic response rates and detecting
      relapses.

PMID- 9157474
TI  - [Radiologic diagnosis of primary extranodal lymphoma manifestations].
AB  - Primary extranodal lymphoma manifestation in the narrow sense is the term used to
      define the primary organ manifestation of a malignant lymphoma, excluding the
      thymus, spleen, Waldeyer's tonsillar ring, the appendix and Peyer's patches.
      However, in the clinical routine the term is also used for the secondary organ
      manifestation of underlying lymphoproliferative disease. Primary extranodal
      lymphomas are mainly non-Hodgkin lymphomas; there is primary extranodal
      manifestation of Hodgkin's disease in only about 1% of the cases. Among the
      extranodal NHL, the highly malignant forms predominate. A major exception is MALT
      lymphomas, which mainly show low slow growth. In the past, they were considered
      to be pseudolymphomas because of their slow and localized tumor growth. They were
      included as an entity of their own for the first time in the Revised European
      American Lymphoma (REAL) classification of 1994. The incidence data vary between
      < 10% and 25% for primary extranodal manifestation. The major reason for this is
      the difference in extranodal regions because of classification. Secondary organ
      involvement of an NHL occurs in up to 40% of the cases in the long-term course of
      the disease in primary nodal lymphomas. Secondary organ involvement is frequently
      diagnosed in AIDS patients who develop an AIDS-related lymphoma (85% of cases).
      The following contribution reports on the radiological imaging of extranodal
      lymphoma manifestation in the thoracoabdominal region.

PMID- 9157475
TI  - [Primary gastrointestinal lymphoma].
AB  - The gastrointestinal tract is the most common extranodal site for non-Hodgkin's
      lymphoma. Primary gastrointestinal lymphoma (PGIL) represents a specific entity
      and has to be differentiated from nodal lymphomas because of its different
      biological behaviour, prognosis and treatment. Imaging methods are important for
      detection and staging of PGIL. Gastrointestinal lymphomas produce a spectrum of
      pathological and radiological appearances. PGIL is encountered often enough to
      warrant familiarity with the clinical, radiological and therapeutic options.

PMID- 9157476
TI  - [Primary malignant lymphoma of the brain].
AB  - Primary malignant lymphoma of the brain is a disease of unknown etiology, which
      is increasing in incidence and has an unfavorable prognosis. Despite the lack of
      specific changes on CT or MRI in most cases, these procedures may typically
      facilitate the diagnosis: a focal-enhancing mass with subependymal spread on CT
      or MRI and hyperattenuation on nonenhanced CT are the most reliable features in
      the diagnosis of primary malignant lymphoma of the brain. Peritumoral edema and
      mass effect are usually not prominent features. On unenhanced CT scans they
      usually appear homogeneously isodense to mildly hyperdense relative to the gray
      matter. On MRI these tumors are slightly hypointense on T1-weighted images and
      slightly hyperintense on PD- and T2-weighted images relative to the gray matter.
      On CT and MRI enhancement is usually homogeneous. Contrast-enhanced MRI, with its
      multiplanar capability, lack of bone-induced artifacts, and high-contrast
      resolution, is likely to reveal subependymal spread and meningeal involvement
      that have escaped detection by CT. Because there are no specific features on CT
      or MRI in most cases, patients who are suspected of having primary malignant
      lymphoma of the brain should immediately undergo biopsy and, if the diagnosis is
      confirmed, whole-brain radiation therapy. With early diagnosis and treatment,
      these patients benefit from radiation therapy.

PMID- 9157477
TI  - [Lymphoma in childhood].
AB  - Manifestation of childhood Hodgkin's disease and Non-Hodgkin's lymphoma differ,
      especially in the latter, from those in adults. Extranodal involvement is seen
      even more frequently in childhood Non-Hodgkin's lymphomas than in adults. This
      article reviews the radiological findings in malignant lymphomas in children,
      explains the differences in the manifestation of Hodgkin's lymphomas, of
      different subtypes and of the malignant lymphomas in adults. The problems in
      diagnosis of organ manifestation and special problems of diagnostic imaging
      procedures in children are discussed.

PMID- 9157478
TI  - [Malignant lymphoma in childhood. Ultrasound diagnosis].
AB  - The sonographic diagnosis of malignant lymphoma in childhood is described.
      Malignant lymphomas are sonographically relatively uniform: initial enlargement
      of the lymph nodes and organs involved and disturbance of normal echo texture by
      mainly hypoechoic lesions can be found. Generally, four sonographic patterns of
      infiltration are described: diffuse, small nodular, large nodular and bulky type.
      Secondary, tumor-related or inflammatory complications (e.g. dislocation or
      compression of vessels, thoracic inlet syndrome, venous thrombosis, ileus,
      urinary retention, abscess and effusion) can be sonographically evaluated.
      Response to therapy correlates with normalization of size and echo texture and
      recovery from tumor-related complications. Differential diagnosis with ultrasound
      is based on the topographic distribution and echo pattern of infiltration and,
      with certain restrictions, on the echogenicity of lesions and perfusion feasible
      with Doppler sonography. The primary diagnosis has to be established
      histologically.

PMID- 9157479
TI  - [Positron emission tomography (PET) in diagnosis and therapy planning of
      malignant lymphoma].
AB  - The management of patients who have malignant lymphomas requires functional
      methods to differentiate residual soft tissue masses. Positron emission
      tomography (PET) was performed in patients with histologically proven malignant
      lymphomas prior to the onset of second-line chemotherapy to examine tumor
      viability. Twenty patients (68 malignant lesions and 3 benign lesions) with
      Hodgkin lymphomas (HL) as well as 26 patients (46 malignant lesions and 1 benign
      lesion) with non-Hodgkin lymphomas (NHL) were studied with fluorine-18
      deoxyglucose (FDG). Oxygen-15-labelled water was used in addition in 14 patients
      with 25 lesions to obtain information on the tissue perfusion. PET with FDG is
      highly sensitive for the detection of viable tumor tissue, all malignant lesions
      being correctly classified in this study. We noted no statistically significant
      difference in FDG metabolism for Hodgkin and non-Hodgkin lymphomas. Even normal
      sized lymph-node metastases (< 1 cm) were detected with PET and FDG. The possible
      limitations are inflammatory processes, which may obscure tumor detection because
      of the increased FDG uptake, as well as malignant lesions with low FDG uptake as
      a result of reduced perfusion. Comparison of tumor perfusion and FDG uptake
      showed a significant nonlinear correlation of r = 0.78 between the two
      parameters. Two patients with scar tissue and no evidence of malignancy were
      excluded from blood stem-cell support therapy as a result of the PET study. The
      data demonstrate that PET is a useful tool for making a diagnosis and deciding on
      therapy for malignant lymphomas.

PMID- 9157480
TI  - [Radiotherapy of Hodgkin's and non-Hodgkin's lymphomas. Indications, techniques
      and outcome].
AB  - The role of radiotherapy in the treatment of Hodgkin's disease and non-Hodgkin's
      lymphoma has changed considerably in the last few decades. Clinical observation
      of mainly unicentric pathogenesis with continuous expansion and subclinical
      involvement of adjoining regions of lymph nodes has resulted in the introduction
      of a large-field technique with total nodal irradiation (TNI) or total lymphatic
      irradiation (TLI). The introduction of polychemotherapy has led to further
      improvement in the cure rate and in considerations concerning using both methods
      and adapting them to the stage and risk. Today the combination of radiation and
      chemotherapy leads to a reduction in the amount of radiation required in the
      affected regions (involved field irradiation = IFI).

PMID- 9157481
TI  - [CT subtraction angiography (CTSA). Results with an automated "elastic"
      subtraction algorithm].
AB  - PURPOSE: To develop and implement a method to obtain digital subtraction (DS)
      spiral computed tomography angiograms (SCTA) in order to avoid superimposition of
      bony structures and vascular calcifications on SCTA maximum intensity projections
      (MIPs) and shaded surface display (SSD). METHOD: Two SCTA data sets, one before
      and one during the injection of a contrast agent bolus, were obtained with
      identical scan parameters. Since ordinary subtraction of the two data sets fails
      to reliably separate bones and calcifications from the vascular lumen because of
      motion, a so-called elastic subtraction procedure was designed to correct 3D
      misregistration between the two data sets. It automatically accommodates for
      local position changes between baseline and contrast images, including regionally
      inconsistent non-linear displacements and arbitrary rotations. This method was
      tested in seven patients and evaluated against ordinary DS in terms of image
      quality and artifacts. RESULTS: In all patients "elastic" CTSA proved superior to
      ordinary DS. It provides automated and reliable separation of vessels from bones
      and calcifications. This improves the delineation of vessels in the neck and the
      skull base and of intracranial vessels. DS-SCTA facilitates MIPs and SSD without
      artifacts introduced by thresholding. CONCLUSION: Elastic DS-SCTA is a robust
      method for automated unmasking of vessels from bones and warrants clinical trials
      and comparison with MR- and conventional angiography.

PMID- 9157482
TI  - [Chronic recurrent ileus. Recurrent mechanical ileus of the small intestine
      caused by a high fiber diet (canned asparagus)].

PMID- 9157483
TI  - [Multi-media presentation of radiologic image data with the Internet].
AB  - AIM: Recent developments of the Internet (World Wide Web) allow the integration
      of audio, video, digital film sequences, and three-dimensional data. The
      applicability of these innovations for medical documentation is demonstrated.
      METHODS: Our existing software for medical image processing and 3D reconstruction
      was extended to provide images, film sequences, and complex 3D models in an
      Internet-compatible data format. RESULTS: The multimedia results of the image
      processing were integrated into Internet documents. Specialized programs are no
      longer necessary for visualization. The Internet software allows for user
      friendly handling and interactive presentation of the 2D and 3D data.
      CONCLUSIONS: The Internet offers public-domain software for display of images,
      audio/video, and 3D data. Thus, the tools of the Internet represent an ideal
      basis for local hospital information systems, computer-aided medical education,
      and teleconferencing.

PMID- 9157484
TI  - Fibromyalgia and chronic fatigue syndrome: similarities and differences.
AB  - CFS and FM are clinical conditions characterized by a variety of nonspecific
      symptoms including prominent fatigue, myalgia, and sleep disturbances. There are
      no diagnostic studies or widely accepted, pathogenic, explanatory models for
      either illness. Despite remarkably different diagnostic criteria, CFS and FM have
      many demographic and clinical similarities. More specifically, few differences
      exist in the domains of symptoms, examination findings, laboratory tests,
      functional status, psychosocial features, and psychiatric disorders. FM appears
      to represent an additional burden of suffering among those with CFS, however,
      underscoring the importance of recognizing concurrent CFS and FM. Further
      clarification of the similarities (and differences) between CFS and FM may be
      useful in studies of prognosis and help define subsets of patients who may
      benefit from specific therapeutic interventions.

PMID- 9157486
TI  - The qmeA (ts) mutation of Escherichia coli is localized in the fabI gene, which
      encodes enoyl-ACP reductase.
AB  - The phenotypes of temperature-sensitive qmeA and fabI mutants of Escherichia coli
      appear to be very similar. Furthermore, the qmeA mutation could be complemented
      by the fabI gene on a plasmid, and the fabI allele derived from the qmeA mutant
      strain harbours a nucleotide substitution identical to that from a previously
      characterized fabI mutant. These results show that the qmeA gene is, in fact,
      identical to the fabI gene, which encodes enoyl-ACP reductase, involved in fatty
      acid elongation.

PMID- 9157485
TI  - In vivo positive effects of exogenous pyrophosphate on Escherichia coli cell
      growth and stationary phase survival.
AB  - We have studied the effect of exogenous pyrophosphate on growing cells of
      Escherichia coli. In the presence of 10 mM of pyrophosphate, the entry into the
      stationary phase was delayed and thus a significant increase in the growth yield
      was observed (25 to 35%) when the bacteria were grown in glucose minimal medium.
      Furthermore, the synthesis of 52 polypeptides was affected, as demonstrated by
      two-dimensional electrophoresis. Among the 22 proteins identified by comparison
      with the E. coli gene-protein index and/or by microsequencing procedures, 15 were
      involved either in catabolic or anabolic pathways of the intermediary metabolism
      or in stress responses. Subsequent physiological experiments enabled us to
      conclude that pyrophosphate exerted a direct or indirect effect on bacterial
      growth by (1) conferring upon cells a better capacity to use carbon sources and
      (2) inducing biosynthetic processes. Finally, we show that exogeneous
      pyrophosphate enhanced the stationary phase survival of E. coli cells.

PMID- 9157487
TI  - Bacteriophage Mu gem2ts, which induces synchronous cell division in the infected
      host, is mutated in the gem operon promoter.

PMID- 9157488
TI  - Genetic analysis of the replication region of the Lactobacillus plasmid vector
      pPSC22.
AB  - The sequence and genetic organization of the 1,600-bp replication region of the
      Lactobacillus vector pPSC22, a plasmid derived from a 7-kb cryptic plasmid of L.
      plantarum used for the cloning of heterologous genes in several lactobacilli,
      were determined. Sequence analysis revealed the presence of a plus origin of
      replication containing the two functional elements nic and bind, required for
      initiation of the leading strands typical of the rolling circle (RC)-replicating
      plasmids belonging to the pLS1 family. Two open reading frames (copA and repA)
      were located within the Lactobacillus portion of pPSC22. The repA gene product, a
      234-amino acid protein, showed homologies with the Rep protein of the
      streptococcal plasmid pLS1 and contained the three conserved domains detected in
      most Rep proteins of RC-replicating plasmids and ss-coliphages. The genetic
      organization of the replication region of pPSC22 shared relevant homologies with
      the lactococcal plasmids pWVO1 and pFX2.

PMID- 9157489
TI  - Characterization of Escherichia coli strains isolated from environmental water
      habitats and from stool samples of healthy volunteers.
AB  - This study was undertaken to determine the frequency of pathogenic Escherichia
      coli strains among wild-type E. coli strain isolates from the microbial flora of
      healthy volunteers and from natural residential water habitats of a defined
      geographic area. In total, 131 stool and 95 water isolates as well as 14 E.coli
      K12 strains were examined for DNA sequences specific for 20 different genes
      encoding E. coli pathogenicity factors, including adherence factors, toxins,
      invasins, capsules and iron uptake systems. The expression of the corresponding
      pathogenicity factors was also investigated. No pathogenicity factors were found
      to be present in the tested E. coli K12 strains. In contrast, 41.0% of the water
      samples and 63.4% of the stool samples contained pathogenicity factors specific
      for extraintestinal E. coli pathogens. While no virulence determinants specific
      for intestinal E. coli pathogens were found among the investigated environmental
      water isolates, 4.5% of the stool samples contained either only intestinal or
      both intestinal and extraintestinal virulence genes. Both the prevalence of the
      virulence genes and the expression of the corresponding pathogenicity factors
      were, in general, higher in stool than in water samples. These findings might
      indicate the prevalence of different clonal types and/or differential regulation
      of pathogenicity factor expression in diverse ecological niches.

PMID- 9157490
TI  - Identification of Listeria species by a semi-nested polymerase chain reaction.
AB  - Three primers derived from the lap gene were used to distinguish Listeria
      monocytogenes from L.innocua and other Listeria species. L. monocytogenes and L.
      innocua yielded a PCR product of 600 and 300 bp, respectively, whereas a typical
      pattern of three amplimers was observed with L. ivanovii, L. seeligeri and L.
      welshimeri.

PMID- 9157491
TI  - Flagellin gene profiling of Campylobacter jejuni heat-stable serotype 1 and 4
      complex.
AB  - Flagellin gene (flaA) sequence polymorphisms were used to discriminate amongst
      167 strains of Campylobacter jejuni serotype HS1 and the HS4 complex. Direct PCR
      of cell suspensions provided a rapid method for analysing DNase-negative strains,
      whereas purified DNA was necessary for the DNase-positive strains. Nine different
      PCR-RFLP patterns (genotypes) were identified by analysis with Hinfl and 12 with
      Ddel, giving a total of 19 combined flaA profile types. The most common combined
      fla types were H1D1 (35%) and H1D2 (20%) for serotype HS1, and H1D2 (23%) and
      H4D7 (43%) for serotype HS4. Comparison of flaA typing with other key subtyping
      methods for C. jejuni showed it to be less discriminatory than pulsed field gel
      electrophoretic (PFGE) profiling, but more so than ribotyping. Fla types provided
      a useful indication of strain diversity, but as some were conserved across
      different serotypes, ribotypes and PFGE types, the same fla type could not be
      used as the sole basis for grouping strains. We provide evidence for several
      distinct subgroups based on conserved multiple genomic criteria within the HS1
      and HS4 strains, and conclude that monitoring of such subgroups could provide a
      novel basis for future epidemiological surveillance of C. jejuni.

PMID- 9157492
TI  - Species attribution and strain typing of Oenococcus oeni (formerly Leuconostoc
      oenos) with restriction endonuclease fingerprints.
AB  - In several wines, malolactic fermentation is required to improve the organoleptic
      characters and to stabilize the final product. In order to establish a controlled
      malolactic fermentation in wine, easy identification and sensitive typing of
      strains of Oenococcus oeni (new name of the malolactic bacterium Leuconostoc
      oenos) used as starter cultures are necessary. To accomplish these tasks, several
      strains of Oenococcus oeni isolated from wines of the Chianti region (Italy),
      along with reference strains and strains of L. mesenteroides subsp.
      mesenteroides, L. carnosum, L. fallax, L. pseudomesenteroides, L. lactis and
      Weisella paramesenteroides, were studied with RFLP of ribosomal genes and
      ultrasensitive total DNA restriction pattern analysis performed on polyacrylamide
      gel. With each of four restriction endonucleases used, identical restriction
      profiles of ribosomal genes were obtained for all strains of O. oeni. These
      ribopatterns, being strongly dissimilar to profiles of the other lactic acid
      bacteria tested, appear to be well suited for the attribution of wine lactic acid
      bacteria to the species O. oeni. Cluster analysis performed on two total DNA
      restriction profile data sets showed that the species O. oeni possesses a good
      degree of genomic homogeneity. Very sensitive typing of strains of O. oeni was
      obtained with total DNA restriction profiles. The potential of an integrated
      approach using restriction profiles for species assignment and typing of selected
      malolactic bacteria is demonstrated.

PMID- 9157493
TI  - Genotyping of Helicobacter pylori isolates by sequencing of PCR products and
      comparison with the RAPD technique.
AB  - Two genotyping methods were performed on bacterial suspensions of the human
      pathogen Helicobacter pylori. A total of 29 clinical isolates were analysed by
      sequencing of a 294-bp PCR-derived internal segment of the essential ureC/glmM
      gene of H. pylori, and by random amplified polymorphic DNA (RAPD) using a single
      11-bp oligonucleotide made up of an arbitrary nucleotide sequence. Each isolate
      exhibited a distinct sequence over a 210-bp stretch of the ureC/glmM gene.
      Similarly, the isolates bore different profiles when tested by RAPD
      fingerprinting. Successive strains arising from patients who relapsed following
      antibiotic treatment and strains isolated from two patients institutionalized in
      the same care centre had identical ureC/glmM gene sequences and RAPD profiles.
      Both methods were found to be discriminatory. However, PCR sequencing of the
      ureC/glmM gene appeared to be more reproducible and more reliable for
      distinguishing between strains than the RAPD technique.

PMID- 9157494
TI  - [What is your diagnosis? Left-sided pleural lipoma].

PMID- 9157495
TI  - [Should heart surgery be refused to children with trisomy 21?].

PMID- 9157496
TI  - [Radiofrequency ablation of supraventricular tachycardia].
AB  - Most forms of supraventricular tachycardia are based on a reentry-mechanism which
      is maintained by a specific anatomic substrate (e.g., dual AV-nodal physiology,
      accessory pathway). Since this substrate is usually a very localized and well
      defined anatomical abnormality, focal thermocoagulation by radiofrequency energy
      is highly effective in restoring normal physiology, thereby offering definite
      cure to a high percentage of these patients. The present article summarizes
      pathophysiologic mechanisms as well as diagnostic electrophysiologic testing- and
      ablation-techniques. Clinical success and complications are discussed in the
      light of current indications for elective radiofrequency ablation of
      supraventricular tachycardias.

PMID- 9157497
TI  - [Ecstasy--the status in French-speaking Switzerland. Composition of seized drugs,
      analysis of biological specimens and short review of its pharmacological action
      and toxicity].
AB  - Methylenedioxy-N-methylamphetamine (MDMA, "Ecstasy") and other related
      phenylethylamines are nowadays used extensively in Western Switzerland at dance
      clubs and raves. There is a widely held belief among teenagers and misusers that
      ecstasy is safe. In the last years however, an increasing number of reports of
      MDMA-related deaths has been reported. Acute clinical toxicity problems following
      MDMA ingestion include hyperthermia, convulsions and arrhythmias. There is also
      growing concern that these phenylethylamines are neurotoxic and cause long-term
      damage to serotonineric nerve terminals in animal brains. Qualitative analyses by
      GC-MS of street samples of ecstasy showed that only a part of them contain MDMA
      or related phenylethylamines (MDA, MDEA, MBDB and 2C-B). Most of them were mixed
      with caffeine and an excipient (sugars or polyols [e.g. mannitol]). Amphetamine
      cut with caffeine and other drugs (e.g. testosterone), stimulants (e.g.
      pseudoephedrine) and other drugs unrelated to stimulants and phenylethylamines
      (e.g. LSD, chloroquine, vasodilators) were also detected. Quantitative
      determinations performed by HPLC-DAD or EC-DAD reveal huge fluctuations in the
      amount of active substance(s) per tablet. MDMA and related compounds display
      unique psychoactive properties, acting as a stimulant and inducing feelings of
      empathy. The effects of MDMA intake are very likely the results of the large
      release of serotonin (5-HT) in the synaptic cleft, of the inhibition of the re
      uptake inactivation of 5-HT and of the inhibition of a key-enzyme involved in the
      biosynthesis of 5-HT. Forensic investigations performed at our institute showed
      significant blood levels of MDMA, MDEA and MDA in samples drawn from people
      suspected of driving under the influence of psychoactive drugs. Up to now, no
      death could be attributed to MDMA intoxication only because our analyses always
      revealed the additional presence of toxic amounts of other psychoactive drugs
      (e.g. opiates, cocaine). Our study shows that because of the variable composition
      of ecstasy tablets, unpredictable types and amounts of drugs may be taken by MDMA
      misusers. Moreover, there is considerable concern that traffic accidents may be
      caused by MDMA-abusers. MDMA intake could result in severe intoxication and even
      death, especially when combined with other types of drugs.

PMID- 9157498
TI  - [Lithotripsy in the conservative treatment of salivary stones].
AB  - Otolaryngologists and generalists as well are commonly involved in the evaluation
      and management of salivary gland stones. Most patients present with a history of
      recurrent swelling and pain in the gland, associated with eating. Up to date
      conservative therapy was limited to the treatment of the acute sialadenitis,
      which may develop as a consequence of the obstruction and often recurs until the
      function of the salivary gland ceases. Surgical treatment depends on the location
      of the calculus. Distal stones can be removed trans-orally by dilatation or
      incision of the duct, whereas those near the hilus and intraglandular stones
      required excision of the gland, including the disadvantage of a scar and the risk
      of injury to cranial nerves. Extracorporal shock wave lithotripsy is a new
      noninvasive method, which allows to destroy intra- and extraglandular salivary
      stones, mostly without the need of local or general anesthesia. Reported
      disintegration rates vary from 14% to 85%, depending on site and size of the
      calculus. About 80% of the patients remain symptomless Lithotripsy of salivary
      stones is a cost-effective, additional treatment modality to surgery and may be
      employed on an outpatient basis.

PMID- 9157500
TI  - [HIV-associated thrombocytopenia].

PMID- 9157499
TI  - [Nephrolithiasis--rational etiological assessment].
AB  - Although underlying metabolic abnormalities do not differ fundamentally in
      patients with either first or recurrent nephrolithiasis and 35% of patients with
      a first event may have to face a recurrence 5 years later, extended metabolic
      investigations in patients with a first renal calculus should be restricted to
      particular, exceptional cases. However, in patients with a first calculus basic
      investigations with respect to specific causes for a concrement such as primary
      hyperparathyroidism, incomplete renal-tubular acidosis, recurrent urinary tract
      infection and cystinuria are mandatory. This includes, in addition to a
      laboratory investigation of blood and urine after a 2-hour-fasting period,
      analysis of the stone and a urography. The extended metabolic investigation in
      patients with recurrences or a first occurrence in a patients with a risk
      constellation includes evaluation of the most important lithogenic (calcium,
      oxalate, phosphate, uric acid) and inhibiting components (citrate) in the 24-hour
      urine, in patients with cystine calculi quantitation of cystine. A metabolic
      investigation should never be undertaken in the hospital or under standardized
      diet, but always under accustomed, unrestricted nutrition. At least 2 urine
      samples should be investigated from each patient, preferably not prior to 3-4
      months after the event when homeostasis of the patient is restored analogously to
      the onset of concrement development.

PMID- 9157501
TI  - [What is your diagnosis?].

PMID- 9157502
TI  - [Does virile climacteric exist?].

PMID- 9157503
TI  - [Pregnancy interruption in Switzerland 1942-1996].
AB  - In spite of restrictive legislation, practice of legal abortion has become
      liberal in Switzerland, bringing illegal abortions to disappear. Moreover, sex
      education and widespread contraception have reduced the number of legal
      abortions. Today, in spite of liberalization, the abortion rate is among the
      lowest worldwide. Prevention targeted specifically at migrant women and spreading
      knowledge about postcoital contraception might reduce it further. Liberalization
      in practice must be followed by liberalizing legislation.

PMID- 9157504
TI  - [Molecular biology detection and antibiotic sensitivities of Shigella spp. and
      entero-invasive Escherichia coli (EIEC) in patients returning from the tropics].
AB  - 1579 stool samples from patients with travel-associated diarrhea were examined by
      conventional culture methods to detect Shigella spp. (48 positive samples or
      3.2%) and by PCR to detect shigellae and enteroinvasive Escherichia coli (EIEC)
      (87 positive samplers or 5.8%). The numerical relation of shigellae to EIEC in
      PCR-positive samples was about 60 to 40%. However, the lack of discrimination
      between shigellae and EIEC is not important for the physician because the choice
      of antibiotics remains the same.

PMID- 9157505
TI  - [The resisting patient--interaction problems in daily clinical practice].
AB  - Resistance presenting as non-compliance is a challenge for daily medical practice
      insofar as this behaviour may have serious negative consequences in the medical,
      health-economic and psycho-hygienic environment of the physician in charge. By
      means of a concrete case-example possibilities for a therapeutically satisfying
      handling of resistance are illustrated. Specific difficulties arising during
      appropriation of conversation technique are pointed out.

PMID- 9157506
TI  - [Therapy-resistant lumbago].
AB  - The 71-year-old female patient was hospitalized owing to a therapy-resistant
      lumbo-spondylogenic syndrome. Radiology with increased infection parameters gave
      rise to the suspicion of a bacterial spondylodiscitis L1/L2. Puncture of the
      vertebral body as well as blood cultures established proof of yersinia
      enterocolitica. In spite of immediate adequate antibiosis, by means of
      "Ciprofloxacin" i.v. spondylodesis of the lumbar spine had to be carried out in
      order meet the threat of instability. Spondylodiscitis is an extremely rare
      manifestation of a yersinia infection, only few cases have been described so far
      in medical literature.

PMID- 9157507
TI  - [Pseudo-gout attack of the right knee].

PMID- 9157508
TI  - [Current AIDS drugs].

PMID- 9157509
TI  - [Growing supply of AIDS drugs].

PMID- 9157511
TI  - [Genes and chromosomes: imaging in genetics].
AB  - FISH methodologies have made spectacular progress and found wide applications in
      several areas of clinical studies and research. These techniques are successfully
      used for visualisation of specific DNA sequences in metaphase chromosomes and
      interphase cells making this approach, with appropriately chosen probes, a useful
      adjuvant to conventional cytogenetics in the study of chromosome abnormalities.
      Improvements have been made in probe generation, developments of new
      fluorochromes, combinatorial and ratio labelling for multicolor signals and novel
      hybridization targets as extended DNA. By varying the probe and the target in
      fluorescence hybridization, numerous applications are being implemented in many
      fields of human genetics, from clinical cytogenetics to the identification and
      study of genes involved in monogenic disorders and oncogenic rearrangements.

PMID- 9157510
TI  - [Functional anatomy of the gene: from gene to protein].
AB  - Over the last 20 years what we knew about genes and their expression has
      considerably evolved. The coding part of the gene is split in several exons
      separated by introns, and preceded by a region of variable size that allows the
      regulation of its expression. From a functional point of view the genes is
      transcribed into a messenger ribonucleic acid which undergoes a maturation
      process. This maturation enables to excise the introns and to add a cap and a
      tail consisting of a poly A. Finally the messenger is transcribed into a protein.
      All these steps undergo multiple and complex regulations.

PMID- 9157512
TI  - [Mechanisms and consequences of genetic mutations].
AB  - Identification of mutations responsible for human monogenic hereditary diseases
      has lately undergone rapid development. It is now possible to establish the
      mutation spectrum for a given genetic disease and international databases are now
      available on the Internet. New mutational mechanisms have been
      identified:transposition, inversion, trinucleotide repeat expansion. At the
      disease level, knowledge of molecular defects has allowed to better delimit
      mechanisms of gain or loss of function, to understand dominant or recessive mode
      of inheritance, to explain anticipation phenomena, to identify founder effect
      amid a selected population, to establish, in some privileged cases, phenotype
      genotype correlations and above all to elicit allelic and genetic heterogeneity
      hitherto unsuspected. Identification of deleterious mutations is also the basis
      of diagnosis at the gene level which today has a growing impact on genetic
      counselling and prenatal diagnosis.

PMID- 9157513
TI  - [Genetic diseases and unstable expansions of trinucleotide repeats].
AB  - More than 10 genetic diseases, including 3 frequent ones (the fragile X mental
      retardation syndrome, myotonic dystrophy and Huntington's disease) are caused by
      unstable expansions of trinucleotide repeats. The instability of these mutations
      and their strong tendency to further expansion, account for the special
      characteristics of the mode of inheritance of these diseases. Unlike most other
      genetic diseases, that can be caused by a large number of different mutations,
      the trinucleotide expansion diseases are due to a single type of mutation.
      Detection of the expansion by DNA analysis allows thus easy and reliable
      diagnosis of these diseases. For several of them, the late but generally very
      deleterious clinical expression, raises the very delicate problem of genetic
      counselling and presymptomatic diagnosis.

PMID- 9157514
TI  - [Animal models of hereditary diseases].
AB  - A large number of genetic diseases are found both in humans and in one or several
      animal species. The mouse is a species of choice since, in addition to hundreds
      of spontaneous mutations which have been described, it is now possible to produce
      at will a mutation in any gene. This strategy has been used to generate
      genetically engineered mice which carry genetic defects found in human molecular
      pathology. Animal models are an invaluable tool to study the pathophysiology of
      diseases and to test new therapies. However, they are rarely exact replicates of
      the human disease. Possible origins for these differences are discussed in
      detail.

PMID- 9157515
TI  - [Developmental genes and dysmorphology].
AB  - Until recently, clinical dysmorphology was the poor parent of clinical medicine
      and human genetics. However, the studies of children affected with multiple
      congenital abnormality syndromes are the first step to recognize syndromes for
      diagnosis identification, leading to prognosis and care for the children and to
      genetic counseling for the family. These studies must lead to the identification
      and analysis of developmental genes involved in normal and abnormal
      morphogenesis. Dysmorphology leads to a better understanding of abnormal
      development, genetic causes and embryological development. The identification of
      different genes from various gene families involved in dysmorphogenesis has
      recently emerged. These developmental genes often act as patterning genes and as
      possible oncogenes; they are of interest for developmental biologists and for
      medical geneticists.

PMID- 9157516
TI  - [Principles and stakes of gene therapy].
AB  - As the human genome sequencing expands and the molecular bases of diseases are
      better understood, the tools that allow gene packaging and transfer are
      available. Transferring a therapeutical gene becomes a reality and indeed more
      than 100 clinical protocols are currently exploring a variety of applications,
      from the inherited genetic diseases such as cystic fibrosis to the acquired ones
      such as cancer. Herein, we describe the different gene transfer strategies
      applied to animals and humans and we present the advantages and limitations of
      the currently available vectors which, today, represent the limiting factor for
      efficient gene therapy.

PMID- 9157517
TI  - [Genetics and society: ethic and legal implications].
AB  - Medical genetics, recently individualised as a full medical specialty, evidences
      new problems issued from its natural and historical developments. Genetics
      counselling, prenatal and predictive diagnosis may be considered as a real
      progress when applied in the strictly medical and individual fields. When
      extended to the whole community to answer collective choices, these technologies
      can turn into eugenic and standardizing practices. Regarding the public health
      and the economic necessity it could be inviting to overpass the essential values
      on which are founded our humanity. In that context laws are required to defend
      the best use for human being several practices, but only after an ethical debate
      in which everyone should participate.

PMID- 9157518
TI  - [Limping in children. Diagnostic orientation].

PMID- 9157519
TI  - [Nosocomial infections. Epidemiology, diagnostic criteria, prevention, principles
      of treatment].

PMID- 9157520
TI  - [Superficial adenopathy. Diagnostic orientation].

PMID- 9157521
TI  - [Disseminated intravascular coagulation. Etiology, diagnosis].

PMID- 9157522
TI  - [Chronic glaucoma. Physiopathology, diagnosis, course, principles of treatment].

PMID- 9157523
TI  - [Aortic stenosis. Etiology, physiopathology, diagnosis, course].

PMID- 9157524
TI  - [80th birthday of Christoph Hedinger].

PMID- 9157525
TI  - [Breathing disorders during sleep: current developments].

PMID- 9157526
TI  - [Early results in the surgical treatment of type B aortic dissection].
AB  - In contrast to type A aortic dissection, the indication for acute surgical repair
      as treatment of choice in type B aortic dissection is not the actual dissection,
      but the complications resulting from the dissection (rupture, potential rupture
      and ischemic syndromes of the aortic branches). Between 1978 and 1994, 92
      patients underwent surgical repair of type B aortic dissection at our
      institution. Following diagnostic confirmation by echocardiography and/or CT
      scan, all patients received conservative antihypertensive therapy. 52% of the
      patients underwent emergency surgical repair. Symptoms prompting surgical repair
      were: visceral ischemia (23%), pleural effusion (19%), paraparesis (17%),
      refractory hypertension (12%), further aortic enlargement (12%), and rupture
      (10%). In chronic type B aortic dissection, the main symptom in 84% of the cases
      was further enlargement of the aorta. The early mortality decreased in the course
      of initial treatment from 33% to 16%, and to 8% after exclusion of patients
      operated on for ruptured aorta. Improved early mortality has led to an increase
      in acute surgical repair. In cases of chronic dissection, strict antihypertensive
      therapy is indicated and regular checks on the width of the aorta, as well
      expeditious diagnostic confirmation of its enlargement, are important.

PMID- 9157527
TI  - [Cannabis poisoning after eating salad].
AB  - We describe 4 patients who suffered gastrointestinal disorders and psychological
      effects after eating salad prepared with hemp seed oil. The concentration of
      tetrahydrocannabinol (THC) in this oil far exceeded the recommended tolerance
      dose. Our observations prompted the Swiss Federal Office of Public Health to
      publish warnings in the press concerning consumption of this oil. We describe the
      symptoms of orally ingested THC and point out unresolved problems connected with
      food containing hemp.

PMID- 9157528
TI  - [Bronchiectasis--current aspects of an old disease].
AB  - Bronchiectasis is pathologically defined as an abnormal and permanent dilatation
      of one or several bronchi. There are localized and generalized types of
      bronchiectasis. A vicious circle hypothesis, including an initial insult to the
      lower airways, impaired mucociliary clearance, microbial colonization/infection,
      bronchial obstruction and a local inflammatory response, has been proposed to
      explain the damage to the bronchial tree and the adjacent lung parenchyma. The
      clinical picture is variable and affected individuals might be asymptomatic or
      suffer from severe respiratory failure. Daily sputum production is the most
      common, though unspecific symptom of bronchiectasis. Other common symptoms are
      hemoptysis and recurrent episodes of sputum purulence, fever and pleurisy.
      Occasionally, major, life-threatening hemoptysis from a ruptured bronchial artery
      occurs. Infectious complications, e.g. lung abscess, empyema, brain abscess, and
      secondary amyloidosis are rarely seen today. The chest radiograph reveals changes
      suggestive of bronchiectasis in the majority of patients with clinically
      important disease. High resolution computed tomography of the lung has almost
      completely replaced bronchography for diagnosis, the latter rarely being of value
      if surgery is contemplated. No etiology is identified in about one- to two-thirds
      of the patients, although there are many diseases eventually associated with
      bronchiectasis. Prevention and therapy of underlying diseases are most important.
      Traditionally, the therapy of symptomatic bronchiectasis is based on antibiotics,
      antibronchoobstructive medication, and chest physical therapy. Surgical resection
      is the treatment of choice for localized symptomatic disease. Bilateral lung
      transplantation should be considered in younger patients with severe, generalized
      bronchiectasis and respiratory failure. Prospective, randomized, largescale
      trials supporting any of the different treatment strategies are not available,
      but antibiotics and surgery probably have improved the long-term outcome of many
      patients with bronchiectasis. In this review, some recent findings regarding the
      classification, pathogenesis, pathology, etiology, diagnosis, treatment, and
      prognosis of bronchiectasis are discussed.

PMID- 9157529
TI  - [Primary hyperthyroidism 1996].
AB  - 55 prospectively documented patients aged 20-84 (median 67) years (47 women, 8
      males) underwent surgery for primary hyperparathyroidism (pHPT). The most
      frequent symptoms and associated conditions were nephrolithiasis (42%) and
      neuropsychiatric symptoms (39%). Only one case of asymptomatic and one case of
      "normocalcemic" pHPT were found in this series. 47 patients (89%) were cured
      following initial neck exploration, and 3 further patients (6%) were cured by a
      second operation. Reoperation also led to cure in 2 patients operated on
      elsewhere in the first instance. 6 patients (11%) had double adenoma
      (bilaterally) and 36% of the adenomas had an ectopic location, with an
      intrathyroidal adenoma in 2 cases. In 2 patients sternotomy was carried out.
      Persistent pHPT was observed in 3 patients (following initial exploration in 2
      cases and reoperation in one). These patients had a supernumerary adenomatous
      gland with ectopic location in 2 cases and a double adenoma with ectopic position
      of one adenoma in a further case. One 80-year-old patient died post-operatively
      from intestinal ischemia. 2 patients had permanent postoperative
      hypoparathyroidism; in no case was a permanent recurrent laryngeal nerve palsy
      observed. Bilateral parathyroid exploration with thyroid mobilization by capsular
      dissection is the procedure of choice for pHPT. In 2 patients with the MEN 2A
      syndrome and with medullary thyroid carcinoma thyroidectomy, lymphadenectomy and
      autotransplantation of normal parathyroids to the arm was performed, with normal
      parathyroid function in both cases.

PMID- 9157530
TI  - [Secondary prevention in chronic coronary heart disease].
AB  - To assess the quality of secondary prevention in patients with known coronary
      artery disease (CAD) we analyzed prospectively 278 consecutive patients on
      admission who were hospitalized for acute coronary syndromes (infarction 46%,
      unstable angina 54%). CAD was known in 155 patients (110 males: acute myocardial
      infarction 50, unstable angina 105; history of infarction 55%, chronic angina
      41%, after CABG 13%, after PTCA 7%, coronary stenoses on angiography 6%). In
      these patients, aspirin was being administered in 58%, anticoagulation in 12%,
      betablockers in 43%, angiotensin converting enzyme inhibitors (ACEI) in 20%, and
      lipid lowering agents in 12%. Calcium blockers were given in 40% (nifedipine 8%).
      Patients with previous invasive diagnosis and treatment were more frequently
      treated with drugs of proven prognostic benefit than patients after myocardial
      infarction and patients with angina only, while overall cardiovascular treatment
      was similar. The respective rates of treatment were: for aspirin 78%, 60% and 39%
      respectively (p = 0.0005); for betablockers 59%, 46% and 24% (p = 0.004); for
      lipid lowering drugs 27%, 7% and 4% (p = 0.002). 12 of 19 patients with known
      congestive heart failure had ACEI. Only one fourth of dyslipidemic patients had
      lipid lowering drugs. We conclude that the prevalence of secondary prophylaxis in
      patients with known CAD is too low despite proven benefit, invasively treated
      patients having better prophylaxis.

PMID- 9157531
TI  - [Splenic infarct, lactate acidosis, and pulmonary edema as manifestations of a
      pheochromocytoma].
AB  - The case of a 45-year-old woman with pheochromocytoma, who presented with severe
      abdominal pain and headache, diabetes mellitus, lactic acidosis and pulmonary
      edema, is described and discussed. Spleen infarction, not so far described as an
      ischemic complication of pheochromocytoma, was seen in computer tomography. After
      medical pretreatment with labetalol, a pheochromocytoma (2 x 2 cm) of the left
      adrenal gland was removed. The postoperative course was uneventful.

PMID- 9157532
TI  - [Ectopic thyroid tissue: an unusual differential diagnosis of space-occupying
      mediastinal lesions].
AB  - The differential diagnosis of soft tissue masses of the anterior mediastinum
      includes cervical goiter extending into the mediastinum, germ-cell tumors, masses
      originating from the thymus, lymphoma and sternal tumors. A rare cause is ectopic
      mediastinal goiter without a link to the cervical thyroid. We report the case of
      a 36-year-old female patient with accidental chest X-ray finding of a large mass
      ([symbol: see text] 7 cm) in the anterior mediastinum. CT showed a hypodense mass
      with homogeneous enhancement and calcifications. There was no evidence of
      invasion in other organs. CT-guided biopsy revealed thyroid tissue. The cervical
      thyroid was normal in CT, ultrasound and 123I-scintigraphy; no link to the
      mediastinal goiter was detectable. Radionuclide uptake in the latter was
      homogeneous. Since malignancy could not be ruled out definitively, the mass was
      removed by thoracotomy and a vascular pedicle originating from the mediastinum
      was found. Pathologic evaluation confirmed the preoperative diagnosis of ectopic
      mediastinal goiter.

PMID- 9157533
TI  - [Blue "diapers"].

PMID- 9157535
TI  - [Procedures and technical aptitude of primary care physicians: which practice?].
AB  - PROBLEM: There is little knowledge of the practices of private physicians in
      Switzerland. However, this knowledge is a prerequisite for definition of the
      learning objectives in post-graduate and continuous education. OBJECTIVE: To
      ascertain the procedural skills of family physicians and general internists and
      compare them with variables such as education and the location of practice.
      METHOD: Questionnaire containing 68 procedural skills sent to all family
      physicians and general internists in the Cantons of Valais (VS) and Geneva (GE).
      RESULTS: 142/204 questionnaires (69%) were analyzed. A mean of 28.7 skills are
      practiced by the physicians. The internists use fewer procedures than the
      generalists. There is no difference between generalists practising in VS and GE,
      nor between location of the practice (urban or rural). The internists in GE
      and/or those practising in urban settings use fewer procedures than those
      practising in VS and in rural locations. Internists practising in rural setting
      use the same number of procedures than the generalists. Fifteen procedures are
      used by > or = 75% of physicians, 6 of these concern X-ray procedures. 60% of the
      procedures are used more frequently by the generalists, in particular surgical,
      ENT and gynecological procedures. There is no difference between generalists and
      internists as far emergency procedures or procedures in the cardiological and
      pneumological domain are concerned. CONCLUSIONS: The number of procedures depends
      nor only on the speciality of the private physician (generalist or general
      internist), but also and mainly on the location of the practice, the density of
      physicians and emergency practice. These findings can be used in defining the
      learning objectives of the primary care curriculum.

PMID- 9157534
TI  - [Benign postural vertigo and nystagmus of the horizontal semicircular canal].
AB  - Benign paroxysmal vertigo and nystagmus are induced not only by the posterior but
      also by the horizontal semicircular canal. Benign positional nystagmus of the
      horizontal canal is more often observed than was previously thought. In 10
      patients we analyzed the characteristics and the variability of nystagmus which
      accompanies positional vertigo of the horizontal canal. There are two forms of
      nystagmus: primary-geotropic, most often paroxysmal nystagmus (7 patients), and
      primary-apogeotropic, non-paroxysmal nystagmus (3 patients). Interestingly, in 2
      patients with the primary-apogeotropic form the nystagmus converted during the
      examination into the primary-geotropic form. The reverse was not observed. We
      discuss the possible pathophysiological mechanisms which could be relevant for
      provoking manoeuvres.

PMID- 9157536
TI  - [Procedures and technical aptitude of primary care physicians: which education?].
AB  - OBJECTIVE: To ascertain the educational goals of internal medicine teachers in
      the domain of clinical skills, the realization of these objectives and their
      pertinence for the practice of primary care physicians. METHODS: Questionnaire
      containing 44 clinical skills sent to the chiefs of the services of internal
      medicine of public hospitals in French-speaking Switzerland and the 5 Swiss
      university hospitals. Comparison of these results with an earlier study
      concerning the practice of clinical skills of the primary care physicians.
      RESULTS: The participation was 82%. The educational goals were identical for all
      the chiefs of internal medicine independently of whether they were university
      dependent or not, or in a large or small hospital. 22 of the proposed clinical
      skills were considered as teaching goals for > or = 70% of the heads of medicine.
      However, they thought that only 8 of these 22 skills were acquired by the
      majority of their residents. 8 of these 22 skills were considered to be
      indispensable for proper functioning of the service. There was a good correlation
      between the acquired skills and those considered to be indispensable for proper
      functioning of the service. The medical chiefs considered most of the skills
      practiced by the primary care physicians were also educational objectives.
      However, they thought that only 23% of these skills were acquired by their
      residents. Only half of the skills considered as acquired were practiced by a
      majority of the primary care physicians. CONCLUSIONS: Many clinical skills are
      considered as educational goals by the medical chiefs of hospital services in
      internal medicine. However, they consider only a third of these goals as acquired
      by their residents at the end of their residency. There was a good correlation
      between the skills thought to be acquired and those considered to be
      indispensable for proper functioning of their service, and a poor correlation
      between the skills considered as acquired and those practiced by primary care
      physicians.

PMID- 9157538
TI  - Common themes amid diversity.

PMID- 9157537
TI  - [Current therapy concepts in cutaneous T-cell lymphomas].
AB  - Cutaneous T-cell-lymphomas (CTCL) include a group of rare diseases that are
      characterized by an accumulation of clonal T-lymphocytes in skin. The various
      disease entities may be classified by an adapted Kiel classification. For staging
      purposes the TNM system is most commonly used. Treatment modalities depend on the
      extent and the aggressiveness of the disease (low- or high-grade lymphoma) and on
      the individual situation of the patient. Stage-adapted therapy is currently
      recommended. Early stages of low-grade CTCL are successfully treated with PUVA,
      retinoids or interferon-alpha. Extracorporeal photopheresis is the treatment of
      choice in stage III patients with Sezary syndrome. Alternative therapeutic
      modalities for CTCL, such as radiotherapy, chemotherapy or various experimental
      protocols, are discussed.

PMID- 9157539
TI  - Review staff at FDA.

PMID- 9157540
TI  - Evidence for linkage disequilibrium between HLA-DRB1 gene and multiple sclerosis.
      The French Research Group on Genetic Susceptibility to MS.

PMID- 9157541
TI  - NCI plans attack on HIV resistance.

PMID- 9157542
TI  - Disclosing data can get you in trouble.

PMID- 9157543
TI  - Montagnier to head New York center.

PMID- 9157544
TI  - Estrogen stakes claim to cognition.

PMID- 9157545
TI  - Force-carrying web pervades living cell.

PMID- 9157546
TI  - New technique maps the body electric.

PMID- 9157547
TI  - A mitochondrial Alzheimer's gene?

PMID- 9157548
TI  - SIV hunt leads to baboon virus discovery.

PMID- 9157550
TI  - Life goes to extremes in the deep earth--and elsewhere?

PMID- 9157549
TI  - Microbiology's scarred revolutionary.

PMID- 9157551
TI  - In industry, extremophiles begin to make their mark.

PMID- 9157552
TI  - PAS, present, and future: clues to the origins of circadian clocks.

PMID- 9157553
TI  - Quenching the spark in the heart.

PMID- 9157554
TI  - The costs of animal research: origins and options.

PMID- 9157555
TI  - Life-sciences R&D, national prosperity, and industrial competitiveness.

PMID- 9157556
TI  - Beating scientists into plowshares.

PMID- 9157557
TI  - [Diagnostic problems in fractures of the occipital condyles].
AB  - Three cases involving fractures of the occipital condyle were recently treated by
      the authors. Since plain radiographs of the upper cervical spine often fail to
      reveal this lesion, it can be difficult to diagnose. It seems to be more common
      than previously suspected and described. We found one axial compression fracture
      and two avulsion fractures with different degrees of atlanto-occipital
      instability. Mandibular fracture occurred in all cases. There was no severe
      craniocervical trauma. The atlanto-occipital junction should always be included
      in the CT evaluation of facial or craniocervical trauma. Thin-section CT of the
      craniocervical region can best visualize this fracture and should be used when it
      is suspected. All cases were treated by orthotic immobilisation.

PMID- 9157558
TI  - [Dislocated multiple fragment fractures of the head of the humerus. Does
      dislocation of the humeral head fragment signify a worse prognosis?].
AB  - PROBLEM: The vascularity of the articular fragment is of key importance for the
      final outcome in three- and four-part fractures of the humeral head. Displacement
      of the articular segment may compromise the arterial blood supply to the humeral
      head and result in avascular necrosis. There is still controversy as to whether
      three-and four-part fracture dislocations (articular fragment outside the
      glenoid) have an even worse prognosis than displaced three- and four-part
      fractures. PATIENTS AND METHODS: Between January 1985 and May 1993, 102 patients
      with three- and four-part fractures of the humeral head were treated by ORIF
      (mostly tension band wiring) at our institution. In a retrospective study we
      analysed the functional (Constant 100 point score) and radiological outcome of 67
      (66%) of these patients. There were 21 patients with fracture dislocations (FD),
      n = 5 type B2X, n = 5 type B3X, n = 3 type C2X, n = 8 type C3X, according to the
      classification of Habermeyer [7]. The "X" represents the dislocation of the
      articular fragment, whereas the classification to each type is done after
      reduction of the head. The remaining 46 patients presented with displaced, but
      not dislocated, three- and four-part fractures (DF), n = 24 type B2, n = 7 type
      B3, n = 3 type C2, n = 12 type C3. Average follow-up was 25 months (7-72 months).
      Patients with FD were significantly younger (average age 50 years) than patients
      with DF (average age 63 years, P < 0.05) and showed a significantly higher
      incidence of traumatic nerve or plexus lesions (FD 19%, DF 2%, P < 0.05).
      RESULTS: Concerning the functional results, there was no statistically
      significant difference between the two groups. The FD patients even showed a
      slight tendency to better results than patients with DF. This was true for the
      three-part fractures (average Constant score 78 versus 67 points), as well as for
      the four-part fractures (average Constant score 62 versus 55 points). The
      significantly younger age of the FD patients may explain their better results.
      The entire group of patients with three-part fractures showed a significantly
      better functional outcome (average Constant score 68 points) than patients with
      four-part fractures (average Constant score 55 points, P < 0.05). The rate of
      partial and total avascular necrosis of the humeral head was strongly correlated
      to the fracture type (number of fragments, fracture of the anatomical or surgical
      neck, according to the classification of Habermeyer),but again there was no
      difference between the FD and DF group (B2X: 20%, B3X: 20%, C2X: 33%, C3X: 63%;
      B2: 25%, B3: 29%, C2: 33%, C3: 67%). Astonishingly, the FD were not associated
      with an increased rate of avascular necrosis of the humeral head. Three (axillary
      nerve) out of the five observed primary nerve and plexus lesions had a full
      neurological recovery after 6-12 months; the two patients with alterations of the
      brachial plexus showed a slow tendency of improvement at follow-up (12 and 18
      months), but still had gross muscular atrophy and impaired sensory function.
      CONCLUSION: In displaced three-and four-part fractures of the humeral head the
      dislocation of the articular segment does not seem to increase the risk of
      avascular necrosis, if treated by timely and careful ORIF with respect to the
      vascularity. Even with the increased risk of primary nerve and plexus lesions in
      fracture dislocations, good functional results can be achieved by early operative
      nerve decompression and fracture stabilization in this middle-aged patient group.
      However, older patients with displaced or dislocated four-fragment fractures
      through the anatomical neck (type C3) have a poor chance of a favourable outcome,
      and therefore primary prosthetic replacement should be considered.

PMID- 9157559
TI  - [Seidel humerus intramedullary nailing. Clinical results of 100 surgeries].
AB  - Between 01.01.88 and 30.07.94 we treated 81 traumatic and 19 pathologic humeral
      shaft fractures with the Seidel humeral locking nail (HLN). The majority of the
      100 patients (60 women, 40 men) were older than 60 years of age. The dominant
      fracture type according to AO was type A. Operative stabilization was considered
      indicate because of fracture distraction during functional bracing in most cases.
      In general, patients choose surgical intervention in preference to conservative
      management. Radiological consolidation was observed within 10 weeks. In 48 cases
      sonography revealed motor disturbances between the gliding sheath of the rotator
      cuff, but there was no correlation between this and the shoulder mobility. In 7
      cases an additional fracture was created during introduction of the nail. This
      complication can be avoided by using the right technique. There were no cases of
      non-union or radial nerve lesion. There were 2 patients who developed an
      infection, which disappeared after removal of the nail and introduction of
      antibiotic-loaded beads. Functional results were recorded in 63 patients: 53
      patients (84%) had an excellent or satisfactory result (NEER score > 80). Among
      the others, problems at the site of nail insertion predominated. In our view, the
      Seidel humeral locking nail is an implant that provides exercise stability
      without intraoperative positioning problems or risk of injury to nerves or
      vessels. Nevertheless, this method needs a skilled surgeon with special training
      to handle typical technical nailing problems.

PMID- 9157560
TI  - [Vascular lesions in surgery of the hip joint].
AB  - The vascular anatomy in the acetabular region involves a certain risk of arterial
      and venous injuries complicating orthopaedic surgery. These complications have
      been grouped into four categories: lacerations, thrombosis, pseudoaneurysms and
      arteriovenous fistula. In a period of 5 years, three injuries of the external
      iliac artery and four lesions of the femoral artery associated with total hip
      arthroplasty were treated surgically at the Department of Vascular Surgery of the
      University Hospital in Graz. In one case a concomitant lesion of the pelvic vein
      was observed. The incidence of iatrogenic vascular injuries in total hip surgery
      is 0.3%. Combined injury of the external iliac artery and vein led to a life
      threatening bleeding complication. The vascular lesion became manifest as acute
      ischaemia of the lower extremity or as an acute haemorrhage 30 min to 2 h after
      primary surgery. The late complication of a false aneurysm of the femoral artery
      occurred in one patient 3 weeks after total hip replacement. Reconstruction of
      the vascular lesions was performed by direct suture, except that two arterial
      lesions required the use of polytetrafluoroethylene (PTFE) vascular grafts.
      Vessels in the pelvic region are at high risk if screw fixation acetabular
      components are used. Perforation of the iliac artery by protruded
      methylmethacrylate polymer components of cement has been documented. The
      obturator vessels are in a vulnerable position if the acetabular floor has been
      broached by operative instruments or eroded by loosening of the prosthesis
      facilitated by osteoporosis, steroids or sepsis. Femoral vessels are endangered
      by Hohmann retractors that are not placed directly on bone. Though vascular
      injury during hip operations is rare, recognition of such complications is
      important as safe and satisfactory treatment can be achieved. Rapid
      identification and immediate surgical repair of these lacerations are essential
      for their management.

PMID- 9157561
TI  - [Unilateral stepwise lengthening osteotomy of the femur].
AB  - Intraindividual length differences up to 1.2 cm in femora, up to 1.0 cm in tibiae
      and up to 1.4 cm in whole leg length can be regarded as physiological. Length
      differences in childhood are frequently compensated for by functional adaptation
      in the chain of adjacent limbs. In adults, however, that adaptability is
      diminished and correction osteotomy after post-traumatic shortening may therefore
      be indicated more generously dependent on local and general criteria of
      operability. A conscientious analysis of bone geometry by clinical means,
      radiology and computed tomography is mandatory for the indication and planning of
      any correction osteotomy. Intraindividual leg length differences of more than 4
      cm are preferentially treated by continuous callus distraction techniques.
      Shortening by less than 4 cm, however, is suitable for a one-stage stepwise
      prolongation osteotomy in the metaphysis of the femur, i.e. in the
      subtrochanteric or supracondylar region. These osteotomies are than stabilized by
      long condylar plates; the bony defects are filled up by auto- or allogenous
      corticospongeous bone. Simple modifications of the stepwise prolongation
      osteotomy permit additional corrections of torsional deviations up to 20 degrees
      or of axial deviations in the frontal or sagittal plane up to 5 degrees. The
      results of 24 one-stage stepwise prolongation osteotomies of the subtrochanteric
      and supracondylar femur after congenital or post-traumatic shortening are
      presented as well as the reason and respective therapies for three important
      complications.

PMID- 9157562
TI  - [Dynamic pedography for assessing functional ankle joint instability].
AB  - Chronic functional instability of the lateral ankle may be difficult to
      distinguish from mechanical instability when radiological stress test reveal only
      small ligamentous defects. When a decision for or against surgical reconstruction
      of the ligaments has to be made it can be helpful to use additional information
      on joint function. Therefore, a prospective study of 65 patients (mean age 24.1
      +/- 4.6 years) with long-standing chronic ankle instability was conducted to
      demonstrate that the dynamic measurement of plantar pressure distribution can
      identify patients with functional ankle instability. Plantar pressure patterns
      were measured during gait by means of a capacitive platform, the EMED-SF system.
      The impulses at eight points of the foot were calculated intraindividually and
      compared with those in a group of 100 healthy subjects. On the basis of clinical
      criteria alone, the two groups of patients were distinguished, 35 with functional
      instability and 30 with mechanical instability. The patients with functional
      instability showed significantly increased lateral loading of the unstable foot
      (P = 0.01), whereas the group with mechanical instability tended to walk more on
      the medial side of the unstable foot. This finding is explained by a deficit or
      peroneal strength during the stance phase, based on a proprioceptive deficit
      after trauma. The new technique provides additional information, which is
      relevant and sufficiently important to help in making decisions about the
      individual patient with chronic instability.

PMID- 9157563
TI  - [Motorcycle accidents in street traffic. An analysis of 86 cases].
AB  - A retrospective study of 86 motorcycle accidents that occurred in the year 1992
      is reported. Examination of the case histories supplemented by telephone
      conversations yielded the following results: 90.7% of our patients were male and
      their average age was 28.8 years; the age group between 25 and 30 years was the
      most frequently involved (27.9%). Most motorcycle accidents happened during
      weekend trips out in the summertime. Special injury patterns were found for
      injuries of the upper and the lower extremity. Lower extremity injuries (46%),
      and especially open tibia fractures (19.7%), were among the most common injuries
      sustained by motorcyclists in crashes. Injuries of the upper extremity most
      frequently took the form of fracture of the distal radius (18.8%). The average
      stay in our hospital was 35.4 days. In 23.4% of cases the patients had to change
      their job after the accident. More than half the crashes happened with
      motorcycles with between 500 and 750 cc stroke volume. Over a third (34.5%) of
      the patients had held their driving licences for more than 8 years. A plea is
      made for more preventive measures, such as better driving instruction, better
      road conditions and legislative changes, against motorcycle crashes. From the
      aspects of cost and the rate of complications it is reasonable to strive for a
      surgical treatment as soon as possible after the crash.

PMID- 9157564
TI  - [Soft tissue infection].

PMID- 9157565
TI  - [Defect fractures of the upper arm and their treatment in difficult
      circumstances. 3 case reports from Ethiopian and Somalian provincial hospitals].
AB  - Gunshot fractures of the extremities often result in large bone defects and
      disability. The reconstruction of the bone is the essential precondition for a
      successful rehabilitation. This is a report on three patients who suffered from
      substantial bone defects of the humerus shaft caused by high-velocity bullets. In
      one patient the injury happened 3 days before admission, in another patient 5
      months before. The third patient had a history of 11 years since the injury with
      numerous operations, bone grafts included. He presented with an infected non
      union. All three patients had a complete radial nerve paralysis right from the
      beginning, as they have reported. Debridement, sequestrectomy and immobilisation
      by an external fixator with a device for compression and distraction were the
      first steps in management, followed by slow compression and, after a free
      interval, by distraction for 1 mm per day over a period of ca. 4 weeks. After
      distraction, one patient had early spontaneous callus formation. Two patients
      received a spongious bone graft, and in one of them decompression of the radial
      nerve was carried out during the operation for bone grafting. Subsequently, all
      three patients showed good callus formation. When strong ossification was visible
      on the X-rays, the fixator was removed and a PoP brace applied. The change from
      the external fixator to an internal fixation by a plate was not necessary and,
      under the prevailing conditions, not even possible. The patients were discharged
      with the brace and encouraged to continue with exercises. When the patients came
      back for a follow-up examination, the fracture sites were stable and the bones
      showed good consolidation. In two cases, the function of the radial nerve was
      nearly completely restored, in the patient with the long history, of course,
      there was no change. All three patients were free of infection. These three cases
      show that, even under the unfavourable conditions of civil war and in hospitals
      of less prosperous countries, the treatment of large bone defects can be
      successful, provided material and sometimes personnel support is, if necessary,
      given to the hospitals dealing with war and accident victims.

PMID- 9157566
TI  - [The internet--its uses in traumatology].
AB  - No other words have obtained such meaning in the computer world as the catchwords
      "Online" and "Internet". The possibilities are innumerable, even in the medical
      field, and therefore we must consider whether trauma and orthopedic surgeons can
      also benefit from this new telecommunications medium. As a result of this
      inquiry, a pilot program has been initiated through an Internet connection at the
      computer center in the University of Ulm to test and define the possibilities of
      the Internet in routine clinical applications and for scientific projects. For
      the surgeon, there is already an abundance of information available: (1) A
      medical search register consisting of more than 20 million words has been
      comprised. the source of such searches could be clinics, individuals
      publications, or even an e-mail answer from a patient's "Help" inquiry. (2) The
      literature can be researched without difficulty on the data highway. (3) It has
      become possible to communicate transfer figures, texts, sound and video data
      within seconds to any connected physician throughout the world over the e-mail
      system. (4) Included in the many scientific news-letters presented in the
      Internet ae also several specified for the surgical field. (5) It has also become
      apparent that a few of the rare German-speaking institutions available on the
      Internet (for example, the AO Institute in Davos, some university departments and
      a few research institutes) offer very detailed "Home Pages". In comparison to the
      American institutions, however, the majority of the German surgical world is not
      yet connected to the Internet. The Internet offers an enormous information
      service that is always available and is accessible worldwide. This information
      can already be used in clinical and scientific applications.

PMID- 9157567
TI  - [Diagnosis of traumatic aortic rupture. Transesophageal echocardiography versus
      computerized tomography].

PMID- 9157568
TI  - [Sudeck's syndrome].

PMID- 9157569
TI  - [Sudeck's syndrome. Was Sudeck right?].
AB  - Reflex sympathetic dystrophy (RSD) is a syndrome affecting an extremity after a
      minor trauma or operation. At the moment there is no consensus about the
      pathogenesis of RSD. In 1942 Paul Sudeck suggested that the signs and symptoms of
      RSD may be provoked by an exaggerated inflammatory response to injury or
      operation of an extremity. His theory found no disciples, as most physicians
      believe that RSD is initiated by an hyperactive sympathetic system. We performed
      various clinical and experimental investigations, including the effects of
      antiinflammatory treatment. The results of these studies support the theory of
      Paul Sudeck.

PMID- 9157570
TI  - [Approaches for a systemic modelling of health programs].
AB  - The aim of this paper is to achieve a systemic model to describe a health
      programme taking into account the influence of the actors. The data were
      collected via interviews with 15 people collaborating on two programmes:
      screening of colorectal cancer using the Hemoccult II test in France, and
      restructuring health services in a district in Guinea. The results stress that a
      public and community health programme can be described as a self-organizing,
      dynamic, observing and observed system. With a systemic approach, a programme can
      be modelled according to three steps. First, preliminaries: although initially
      motivated by the wish to improve the system, the intervention on it meets with
      resistance to any change. This stage proposes to open an "intervention space"
      including the definition of an appropriate framework, and the modelling of the
      problematic situation. Second, change: this stage brings new standards in the
      system. The more useful, the more suited to the mind of the collaborators and the
      more integrated into the existing social networks, the more easily the changes
      are welcomed. Finally, autonomization: the regulations of the system contribute
      to maintain the new standards, and thus to strengthen the changes. In conclusion,
      in the initial purpose to improve its operational capabilities, an intervention
      on a local part of the social and health system may, on the contrary, cause
      troubles. The systemic approach proposes a scenario in order to deal with this
      complexity. It also gives new insights for planning, implementing, and assessing
      health programmes.

PMID- 9157571
TI  - Haemostasis in fish--an evolutionary perspective.

PMID- 9157572
TI  - HLA class II profile: a weak determinant of factor VIII inhibitor development in
      severe haemophilia A. UKHCDO Inhibitor Working Party.
AB  - The risk of developing factor VIII inhibitor antibodies in haemophilia A may
      relate both to factor VIII genotype and genes within the HLA complex known to
      influence immune response. We investigated a cohort of 176 patients with severe
      haemophilia A and with either high-level inhibitors (> 10BU/ml) or with no
      history of an inhibitor, stratified according to the presence or absence of the
      factor VIII gene intron 22 inversion. HLA DRB1, DQA1 and DQB1 polymorphisms were
      determined by PCR. HLA frequencies form 137 United Kingdom controls were used for
      comparison. HLA phenotype frequency differences, expressed as odds ratios with
      95% confidence intervals were as follows: HLA-DRB*1501, DQB1*0602 and DQA1*0102
      were all increased in frequency in patients with inhibitors, only DQA1*0102
      reaching statistical significance (OR 2.7, 1.2-5.9). These alleles form part of
      an established HLA haplotype. The frequencies of HLA-DRB1*1501, DQB1*0602 and
      DQA1*0102 were particularly raised in patients with inhibitors and a factor VIII
      gene intron 22 inversion, although again only DQA1*0102 achieved significance (OR
      3.1, 1.0-10.1). The frequency of DRB1*01, DQB1*0501, DQA1*0101 were also
      increased in inhibitor patients lacking the intron 22 inversion although this
      failed to achieve statistical significance. This data suggests that HLA class II
      profile constitutes a weak risk factor for developing inhibitor antibodies to
      factor VIII. This may be more pronounced in patients with an intron 22 inversion.

PMID- 9157573
TI  - HLA genotype of patients with severe haemophilia A due to intron 22 inversion
      with and without inhibitors of factor VIII.
AB  - Molecular genetic studies have shown that development of antibodies to factor
      VIII (inhibitors) occurs most frequently in patients with severe haemophilia due
      to major gene lesions including inversions, stop codons and large deletions.
      Previous studies of HLA type were performed on inhibitor and non-inhibitor
      patients with diverse uncharacterized mutations which may have confounded
      detection of significant associations. We therefore selected a group of patients
      with a single mutation type, the prevalent intron 22 inversion, with or without
      inhibitors, to determine HLA genotype. Seventy-one such patients, 42 without and
      29 with inhibitors (13 high, 9 low and 7 transient responders) were genotyped for
      MHC Class I HLA-A, -B, -C and Class II HLA-DQA, -DQB and -DRB loci. No strong
      correlation of any HLA-allele to inhibitor or non-inhibitor status was found.
      However, alleles of the haplotype HLA-A3, HLA-B7, HLA-C7, HLA-DQA0102, HLA
      DQB0602, HLA-DR15 occurred more often in inhibitor patients. Since the alleles of
      this extended haplotype are common in the North European population only a very
      strong association would achieve statistical significance. Further studies of
      groups of patients similar to those studied here will be needed to confirm or
      exclude this association.

PMID- 9157574
TI  - A novel missense mutation in the endoglin gene in hereditary hemorrhagic
      telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder
      characterized by multisystem vascular dysplasia and recurrent hemorrhage. Recent
      investigation has mapped one of the responsible genes for HHT to chromosome 9q33
      q34; subsequently, nine different mutations have been identified in the endoglin
      gene, which encodes a transforming growth factor beta (TGF-beta) binding protein,
      in nine unrelated families with HHT. We examined the endoglin gene in a Japanese
      patient with HHT and her family members. Using PCR-SSCP analysis followed by
      sequencing, we identified a C to A missense mutation in exon 4 which changed an
      Ala160 codon(GCT) to an Asp160 codon (GAT). Since this mutation destroys one of
      three Fnu4H 1 sites in exon 4, the Fnu4H I digestion patterns of the PCR
      amplified exon 4 fragments from each family member were analyzed. In affected
      members, the restriction patterns were all consistent with a phenotype of HHT.
      PCR-amplified exon 4 fragments from 150 normal individuals were also analyzed by
      allele-specific oligonucleotide hybridization analysis. As a result, the mutation
      was not found in any of them. We conclude that the C to A mutation in exon 4 of
      the endoglin gene in this proband is responsible for the occurrence of HHT in
      this family.

PMID- 9157575
TI  - A common thrombomodulin amino acid dimorphism is associated with myocardial
      infarction.
AB  - Endothelial dysfunction and haemostatic imbalance are believed to be important
      aetiological factors in the development of acute coronary syndromes.
      Thrombomodulin (TM) is an integral membrane protein crucial for normal
      endothelial function and activation of the protein C anticoagulant pathway. We
      have investigated the importance of a common C/T dimorphism in the TM gene
      (nucleotide 1418) for development of premature myocardial infarction (MI). The
      C/T dimorphism predicts an Ala455 to Val replacement in the sixth EGF-like domain
      of TM. The dimorphism was investigated in 97 MI survivors and 159 healthy
      controls. The C allele was significantly more frequent among patients than
      controls (p = 0.035). The allele frequency for the C allele was 0.82 in the
      patients and 0.72 in the control group. The plasma concentration of TM was
      investigated among healthy controls but was not related to the C/T dimorphism. In
      conclusion, the association of the C allele with premature MI, suggests that the
      TM gene and the C/T dimorphism may be aetiological factors involved in the
      pathogenesis of MI. Possibly, the Ala455 to Val replacement may affect the
      function of the TM molecule and the activation of the protein C anticoagulant
      pathway.

PMID- 9157576
TI  - Molecular characterization of a type I quantitative factor V deficiency in a
      thrombosis patient that is "pseudo homozygous" for activated protein C
      resistance.
AB  - Resistance to activated protein C (APC), which is associated with the FV Leiden
      mutation in the large majority of the cases, is the most common genetic risk
      factor for thrombosis. Several laboratory tests have been developed to detect the
      APC-resistance phenotype. The result of the APC-resistance test (APC-sensitivity
      ratio, APC-SR) usually correlates well with the FV Leiden genotype, but recently
      some discrepancies have been reported. Some thrombosis patients that are
      heterozygous for FV Leiden show an APC-SR usually found only in homozygotes for
      the defect. Some of those patients proved to be compound heterozygotes for the FV
      Leiden mutation and for a type I quantitative factor V deficiency. We have
      investigated a thrombosis patient characterized by an APC-SR that would predict
      homozygosity for FV Leiden. DNA analysis showed that he was heterozygous for the
      mutation. Sequencing analysis of genomic DNA revealed that the patient also is
      heterozygous for a G5509-->A substitution in exon 16 of the factor V gene. This
      mutation interferes with the correct splicing of intron 16 and leads to the
      presence of a null allele, which corresponds to the "non-FV Leiden" allele. The
      conjunction of these two defects in the patient apparently leads to the same
      phenotype as observed in homozygotes for the FV Leiden mutation.

PMID- 9157577
TI  - Factor V Leiden is not common in children with portal vein thrombosis.
AB  - Portal vein thrombosis (PVT) is a rare condition affecting both children and
      adults, and occurs in association with a wide variety of clinical situations. On
      the other hand, the development of PVT in patients under these situations
      indicates that other contributing factors could be involved. Recently a missense
      mutation in the factor V gene (1691G-->A), known as factor V Leiden, has been
      identified and results in abnormal factor V product, resistant to proteolytic
      inactivation by activated protein C and thus predisposes to thrombosis. This
      study was carried out to verify if children with PVT have an increase in
      frequency of factor V Leiden. Allele-specific restriction analysis and single
      strand conformational polymorphism (SSCP) were used to test for factor V Leiden
      in 20 children with PVT and 64 normal children. None of the PVT children were
      heterozygous or homozygous for the factor V Leiden, and one control child was
      heterozygous. This study demonstrates that factor V Leiden is not common in
      children with PVT, and is not a prerequisite for this thrombotic event.

PMID- 9157578
TI  - Reliability of five rapid D-dimer assays compared to ELISA in the exclusion of
      deep venous thrombosis.
AB  - Studies measuring the fibrin degradation product D-Dimer (DD) using enzyme-linked
      immunosorbent assays (ELISA) in patients with venographically proven deep venous
      thrombosis (DVT) suggest that it is possible to exclude DVT when DD level is
      below a certain cut-off level. However, ELISA methods are time-consuming and not
      available in all laboratories. Different rapid latex-agglutination assays have
      been investigated, but their sensitivity is considerably lower. In the present
      study we compared the value of four novel latex DD tests (Tinaquant, Minutex,
      Ortho and SimpliRed) and one rapid ELISA (VIDAS) to a classical ELISA DD assay
      (Organon Mab Y18) in 132 patients suspected of DVT. The VIDAS, a new quantitative
      automated ELISA, had a sensitivity of 100% and a negative predictive value of
      100% for both proximal and distal DVT at a cut-off level of 500 ng/ml. The
      Tinaquant assay, a new quantitative latex method, had a sensitivity of 99% and a
      negative predictive value of 93% for both proximal and distal DVT at a cut-off
      level of 500 ng/ml. For proximal DVT only, both assays had a sensitivity and
      negative predictive value of 100%. VIDAS and Tinaquant correlated well with ELISA
      (correlation of r = 0.96 and r = 0.98 respectively). Sensitivities of the semi
      quantitative latex assays Minutex, Ortho and SimpliRed were considerably lower
      (77%, 51% and 61% respectively). These results suggest that VIDAS and Tinaquant
      may be used instead of ELISA DD in the exclusion of DVT. Tinaquant can be
      performed within 20 min and VIDAS within 35 min. Both assays might be used as a
      routine screening test and should be evaluated in large clinical management
      studies.

PMID- 9157579
TI  - Coagulation activation markers in the prediction of venous thrombosis after
      elective hip surgery.
AB  - BACKGROUND: Despite prophylaxis, deep vein thrombosis (DVT) after hip surgery
      continues to occur frequently. Thus it would be helpful if before surgery
      patients at higher risk of DVT could be identified and more adequate prophylaxis
      given. As part of an international study on the prevention of DVT after total hip
      replacement, we investigated whether preoperative levels of three coagulation
      activation markers, prothrombin fragment F1 + 2 (F1 + 2), thrombin-antithrombin
      III complexes (TAT) and D-dimer, correlate with results of postoperative
      venography. METHODS: 159 patients undergoing total hip replacement were
      randomized to receive 10, 15 or 20 mg desirudin bid or 5000 IU unfractionated
      heparin tid immediately before surgery and then for 11 days, until bilateral
      venography was performed. Preoperative F1 + 2, TAT and D-dimer plasma levels were
      measured using ELISA procedures. As no difference among anticoagulant treatments
      or in the interaction between treatments and DVT was detected for any of the
      three variables, results are reported as pooled data. FINDINGS: The frequency of
      DVT was 18.8% in the low (0.75-1.33 nM) vs 65.7% in the high third of
      distribution (1.77-3.47 nM) of F1 + 2 (p < .001), 27.3% in the low (2.00-2.50
      micrograms/l) vs 57% in the high third (5.10-61.00 micrograms/l) of TAT (p =
      .042), and 29.4% in the low (39-59 micrograms/l) vs 57.1% in the high third (129
      651 micrograms/l) of D-dimer (p = .051). INTERPRETATION: Preoperative F1 + 2, TAT
      and D-dimer levels are associated with the risk of development of DVT after total
      hip replacement.

PMID- 9157580
TI  - Coagulation and fibrinolytic profile of paediatric patients undergoing
      cardiopulmonary bypass.
AB  - The haemostatic system and the use of heparin during cardiopulmonary bypass (CPB)
      have been studied extensively in adults but not in children. Results from adult
      trials cannot be extrapolated to children because of age-dependent physiologic
      differences in haemostasis. We studied 22 consecutive paediatric patients who
      underwent CPB at The Hospital for Sick Children, Toronto. Fibrinogen, factors II,
      V, VII, VIII, IX, XII, prekallikrein, protein C, protein S, antithrombin (AT),
      heparin cofactor II, alpha 2-macroglobulin, plasminogen, alpha 2-antiplasmin,
      tissue plasminogen activator (tPA), plasminogen activator inhibitor, thrombin-AT
      complexes (TAT), D-dimer, heparin (by both anti-factor Xa assay and protamine
      titration) and activated clotting time (ACT) were assayed perioperatively. The
      timing of the sampling was: pre heparin, post heparin, after initiation of CPB,
      during hypothermia, post hypothermia, post protamine reversal and 24 h post CPB.
      Plasma concentrations of all haemostatic proteins decreased by an average of 56%
      immediately following the initiation of CPB due to haemodilution. During CPB, the
      majority of procoagulants, inhibitors and some components of the fibrinolytic
      system (plasminogen, alpha 2 AP) remained stable. However, plasma concentrations
      of TAT and D-dimers increased during CPB showing that significant activation of
      the coagulation and fibrinolytic systems occurred. Mechanisms responsible for the
      activation of haemostasis are likely complex. However, low plasma concentrations
      of heparin (< 2.0 units/ml in 45% of patients) during CPB were likely a major
      contributing etiology. ACT values showed a poor correlation (r = 0.38) with
      heparin concentrations likely due to concurrent haemodilution of haemostatic
      factors, activation of haemostatic system, hypothermia and activation of
      platelets. In conclusion, CPB in paediatric patients causes global decreases of
      components of the coagulation and fibrinolytic systems, primarily by
      haemodilution and secondarily by consumption.

PMID- 9157581
TI  - Massive fibrin formation with consecutive impairment of fibrinolysis in patients
      with out-of-hospital cardiac arrest.
AB  - Hypoxia and ischaemia influence blood coagulation and fibrinolysis. This study
      has been made to determine whether human cardiopulmonary arrest causes fibrin
      formation and reduction of fibrinolysis. Serial levels of fibrinopeptide A (FPA),
      fibrinopeptide B beta 15-42 (FPB beta 15-42), D-dimer, tissue plasminogen
      activator antigen concentration (t-PA antigen), t-PA activity, plasminogen
      activator inhibitor-1 antigen concentration (PAI-1 antigen), and PAI-1 activity
      were determined in 63 patients with out-of-hospital cardiopulmonary arrest. In
      the resuscitated patients, the markedly elevated FPA (194.8 +/- 54.2 ng/ml) at
      the beginning of cardiopulmonary resuscitation (CPR) significantly decreased to
      32.4 +/- 9.1 ng/ml at 24 h after admission (p < 0.01), however, this was still
      about 20 times that of the normal controls. FPB beta 15-42 and D-dimer increased
      from the start of CPR to 60 min (189.3 +/- 97.4 ng/ml; p < 0.01 and 7726 +/- 3556
      ng/ml; p < 0.001, respectively), and then decreased at 24 h after arrival at the
      Emergency Department (40.4 +/- 11.1 ng/ml and 5434 +/- 1049 ng/ml, respectively).
      At 30 min after arrival, FPA and FPB beta 15-42 significantly differed between
      the resuscitated patients and the patients who died (p < 0.001 and P < 0.05,
      respectively). Although t-PA antigen and t-PA activity was elevated at the time
      of arrival, 24 h thereafter, no-t-PA activity was detected. At 24 h after
      admission, PAI-1 antigen and PAI-1 activity were significantly increased (472.2
      +/- 145.5 ng/ml; p < 0.001 and 103.6 +/- 36.1 IU/ml; p < 0.001, respectively). In
      conclusion, during and after CPR in patients with out-of-hospital cardiac arrest,
      massive fibrin generation with consecutive impairment of fibrinolysis were
      observed. These fibrin-mediated events may have some role in the derangement of
      vital organ function after cardiac arrest.

PMID- 9157582
TI  - An evaluation and improvement program for inpatient anticoagulant control.
AB  - To improve the management and therapeutic control of inpatients on anticoagulant
      drugs, combined prescription and monitoring charts have been developed for both
      heparin and warfarin which incorporate clinical guidelines. These have been
      introduced throughout a 700-bedded acute teaching hospital via a structured
      program of change management. We have demonstrated improvements in the quality of
      anticoagulant control (assessed with a custom-written computer program),
      adherence to clinical guidelines and quality of monitoring and prescribing of
      anticoagulants in inpatients. The percentage time spent under-anticoagulated with
      heparin (activated partial thromboplastin time ratio < 1.5) fell from 32.7% to
      18.5% (p < 0.0001), whereas there was no change in percentage time over
      anticoagulated (5.1% vs. 5.8%; p = ns). The percentage time spent under
      anticoagulated with warfarin was unaltered (26.3% vs. 29.8%; p = ns) but the
      percentage time spent over-anticoagulated (International Normalised Ratio > 4.5)
      was halved from 5.4% to 2.7% (p < 0.001). We conclude that the introduction of
      the charts led to significant improvements in anticoagulant control.

PMID- 9157583
TI  - Plasma macrophage colony-stimulating factor and P-selectin levels in malaria
      associated thrombocytopenia.
AB  - Thrombocytopenia is a common finding in malaria. In clinical trials, recombinant
      macrophage colony-stimulating factor (M-CSF) causes a reversible, dose-dependent
      thrombocytopenia, and high M-CSF has been reported in autoimmune
      thrombocytopenias. P-selectin, which is secreted into the plasma following
      platelet/endothelial activation or damage, is elevated in certain consumptive
      thrombocytopenic disorders. The relationships between thrombocytopenia, M-CSF and
      P-selectin were analysed in 63 patients with severe (n = 13) or uncomplicated (n
      = 26) P. falciparum (PF) or P. vivax (PV) malaria (n = 24). On admission, 69% of
      PF patients and 75% of PV patients were thrombocytopenic (platelets < 150 x
      10(9)/l). M-CSF was elevated in PF (3021 +/- 1844 pg/ml) and PV (2602 +/- 1668
      pg/ml) patients, compared to controls (589 +/- 200 pg/ml). The platelet count was
      inversely correlated with M-CSF in PF (r = -0.681), and in PV malaria (r = 
      0.548). Elevated P-selectin was found in severe PF malaria, but not in PV
      malaria. Severe PF malaria was associated with marked thrombocytopenia, very high
      M-CSF, elevated P-selectin and compelling evidence of disseminated intravascular
      coagulopathy (DIC). Platelet counts, M-CSF and P-selectin returned to control
      values in 7-14 days. These data suggest that elevated M-CSF in malaria, by
      enhancing macrophage activity, may result in increased macrophage-mediated
      platelet destruction. Further, platelet/endothelial activation or damage, as
      measured by P-selectin, or DIC could intensify thrombocytopenia in severe PF
      malaria, but does not appear to contribute to thrombocytopenia in uncomplicated
      PF or PV malaria.

PMID- 9157584
TI  - Qualitative platelet 12-lipoxygenase abnormality in a patient with essential
      thrombocythemia.
AB  - Quantitative platelet 12-lipoxygenase (12-LOX) deficiency has been reported in
      some patients with myeloproliferative disorders (MPD). We report here for the
      first time a novel qualitative abnormality of the 12-LOX enzyme of platelets from
      a patient with essential thrombocythemia. The anti-12-LOX immunoprecipitates from
      the patient's platelet homogenates showed a deficiency of 12-LOX activity, but
      contained normal amount of 12-LOX protein. There was no difference in subcellular
      localization of the enzyme between the patient's platelets and normal ones. This
      12-LOX protein lacking its enzyme activity showed slightly larger electrophoretic
      mobility than normal one, suggesting a molecular abnormality of the enzyme.
      However, we could not detect any genetic mutation causing such abnormalities in
      all exons of 12-LOX gene by sequencing the patient's PCR-amplified DNA. Thus, our
      results indicate that the deficient activity of this abnormal 12-LOX protein is
      probably due to a posttranslational modification, and the possibility that
      platelets of some MPD patients have qualitative abnormality of the 12-LOX enzyme
      besides quantitative ones.

PMID- 9157585
TI  - Recombinant, B-domain deleted factor VIII (r-VIII SQ): pharmacokinetics and
      initial safety aspects in hemophilia A patients.
AB  - The pharmacokinetics of a second-generation recombinant B-domain deleted factor
      VIII (FVIII) preparation (r-VIII SQ) were studied in 36 patients with severe
      hemophilia A. In contrast to full-length recombinant FVIII, no albumin needs to
      be added to stabilize the final formulation of this B-domain deleted FVIII
      preparation. The in vivo recovery and half-life of r-VIII SQ were similar to
      those of plasma-derived (pd) FVIII (mean half-life of r-VIII SQ, 11.7 h). The
      volume of distribution and clearance were slightly, but significantly, higher for
      r-VIII SQ than for pdFVIII (p < 0.05). Peak plasma levels of FVIII were
      consistently related to the administered dose of r-VIII SQ (r = 0.94, p <
      0.0001). The pharmacokinetic profile of r-VIII SQ remained essentially unchanged
      in a dose range of 25-100 IU/kg body weight and could be reproduced after
      repeated doses. r-VIII SQ was well tolerated. In conclusion, deletion of the B
      domain of FVIII does not influence its in vivo pharmacokinetics.

PMID- 9157586
TI  - Differential effects of reconstituted high-density lipoprotein on coagulation,
      fibrinolysis and platelet activation during human endotoxemia.
AB  - High-density lipoproteins (HDL) can bind and neutralize lipopolysaccharides (LPS)
      in vitro and in vivo. HDL can also affect fibrinolytic activity and can directly
      influence platelet function by reducing platelet aggregation. In this study, the
      effects of reconstituted HDL (rHDL) on LPS-induced coagulation, fibrinolysis and
      platelet activation in humans were investigated. In a double-blind, randomized,
      placebo-controlled, cross-over study, eight healthy male volunteers were injected
      with LPS (4 ng/kg) on two occasions, once in conjunction with rHDL (40 mg/kg,
      given as a 4 h infusion starting 3.5 h prior to LPS injection), and once in
      conjunction with placebo. rHDL significantly reduced LPS-induced activation of
      coagulation (plasma levels of prothrombin fragment F1 + 2) and fibrinolysis
      (plasma levels of tissue type plasminogen activator antigen, t-PA). No effect was
      observed on LPS-induced inhibition of the fibrinolytic pathway (PAI-1) or on the
      transient thrombocytopenia elicited by LPS. Furthermore, rHDL treatment
      significantly enhanced the inhibition of collagen-stimulated inhibition of
      platelet aggregation during endotoxemia, but had no such effect on arachidonate
      stimulated platelet aggregation. rHDL treatment per se also reduced collagen
      induced platelet aggregation. These results indicate that rHDL modifies the
      procoagulant state associated with endotoxemia.

PMID- 9157587
TI  - The effect of factor Xa/phospholipid infusion on the acute phase response in
      baboons.
AB  - Disseminated intravascular coagulation (DIC) is a frequent complication of
      septicemia or tissue injury and may be accompanied by elevations of interleukin
      6, a mediator of the acute phase response. It is not known whether thrombin or
      fibrin deposition may directly induce an acute phase response. To study this, we
      employed a baboon model of in vivo thrombin generation, induced by the
      administration of purified bovine Factor Xa and phospholipid vesicles. Two
      Xa/phospholipid dosages were used, a low dosage (2 animals) leading to a rapid
      49% decrease in fibrinogen and a high dosage (two injections at 5h interval; 3
      animals) leading to complete fibrinogen depletion. Thereafter, fibrinogen levels
      increased in both treatment groups, reached a maximum of 2.52 +/- 0.23 g/l (mean
      +/- SE, n = 5; p < 0.01 with respect to basal levels) at day 2, and returned to
      normal by day seven. In five control (injection of 0.15% NaCl) baboons no
      significant changes of fibrinogen were observed (maximal values: 1.88 +/- 0.12
      g/l). Serum concentrations of C-reactive protein, an acute phase protein,
      increased from 3.7 +/- 0.4 mg/l to a maximum of 33.0 +/- 7.3 at day one, which
      was five-fold higher (p < 0.01) than in control animals at day one (6.2 +/- 0.5
      mg/l). Transient increases were observed within 6h for interleukin-6 from basal
      values of 6.2 +/- 1.7 ng/l to peak plasma levels of 42.9 +/- 21.4 ng/l, a value
      three-fold higher (p = 0.07) than in control animals (14.8 +/- 4.0 ng/l). The
      preliminary results of this observational study suggest that factor
      Xa/phospholipid infusion is followed by an acute phase response, leading after
      one day to significant increases of fibrinogen and of C-reactive protein.

PMID- 9157588
TI  - The activity of unfractionated heparin and low molecular weight heparins in
      rabbit plasma--the need for using absolute anti-factor Xa and antithrombin
      activities.
AB  - Rabbit being a common animal model to evaluate the antithrombotic effect of
      heparins, our purpose was to apply the heparin Standard Independent Unit (SIU)
      approach to rabbit plasma. To take into account the specificities of the enzymes
      we have measured the decay constants of factor Xa and of thrombin from autologous
      and heterologous origins, in presence and in absence of heparin. Different
      heparins or heparin fractions with a mean molecular weight from 1.7 to 10.5 kDa
      were used. We found that: a) the decay constants varied strongly between species
      and between enzymes; b) the decay constants of thrombin were always higher than
      those of factor Xa; c) the specific anti-factor Xa activity of heparins increased
      with the molecular weight and was 1.33 times higher when determined with bovine
      factor Xa than with rabbit factor Xa; d) the specific antithrombin activity of
      heparins also increased with the molecular weight but was similar when determined
      with rabbit and human thrombin; e) the specific anti-factor Xa activity was
      always lower than the specific antithrombin activity; f) the calibration of the
      heparins and heparin fractions against the 4th International Standard of Heparin
      expressed in International Units (IU) lead to a systematic overestimation of the
      anti-factor Xa activity and to an under-estimation of the antithrombin activity.
      These observations indicate that it may be very important to use the SIU approach
      and to know the accurate activities to better understand the mechanism of the
      antithrombotic activity of heparins in experimental models.

PMID- 9157589
TI  - Production method affects the pharmacokinetic and ex vivo biological properties
      of low molecular weight heparins.
AB  - Low molecular weight (LMW) heparins have prolonged circulating half-lives
      relative to unfractionated heparin, but the rates of plasma clearance differ
      between different LMW preparations. To determine the impact of method of
      production on their pharmacokinetic and ex vivo biological properties, two LMW
      heparins of similar molecular weight distribution, Logiparin and Fragmin, were
      radiolabelled with 125I, administered intravenously with 4 mg/kg of carrier drug
      into rabbits, and the circulating radiolabelled material and anti-Xa activity
      were analysed by size exclusion chromatography and affinity for antithrombin and
      Polybrene. Following administration of Logiparin, the anti-Xa amidolytic activity
      was eliminated with the same half-life as the anti-thrombin-binding radiolabel
      and was not neutralised by antibody against tissue factor pathway inhibitor
      (TFPI). Larger molecules were cleared preferentially and were no longer
      detectable 8 h post injection. These findings resemble those we have previously
      described for Enoxaparin. After Fragmin administration the antithrombin binding
      radiolabel was cleared more rapidly than the anti-Xa activity, and at late times
      after injection a significant amount of this activity was neutralised by antibody
      against TFPI. Sulphated radiolabel was eliminated with a similar half-life to the
      anti-Xa activity and sulphated molecules > 6000 Da remained in the circulation 8
      h after administration. Fragmin, unlike Logiparin and Enoxaparin, has no
      negatively charged sulphamino group at the reducing end of the molecule. We
      suggest that this minimises cellular interaction and protects the larger
      molecules from elimination. They remain in the circulation, contributing to anti
      Xa activity by binding TFPI. Thus the method of production of LMW heparins may
      significantly influence their pharmacokinetic properties and circulating
      anticoagulant activities.

PMID- 9157590
TI  - Commercial antithrombin concentrate contains inactive L-forms of antithrombin.
AB  - The preparation of antithrombin concentrate for clinical use requires a viral
      inactivation step. In most commercial preparations this is achieved by heat
      pasteurisation. This process would be expected to alter the conformation of
      antithrombin from the active native species to an inactive latent (L-form) state
      (1, 2). To determine if this occurs during commercial preparation and to identify
      the proportion of the product in the inactive state, we examined the various
      antithrombin conformations within a therapeutic concentrate. The antithrombin
      concentrate was separated into five fractions by heparin-Sepharose
      chromatography. The fraction with the highest heparin affinity retained full
      activity, whereas the four fractions with reduced heparin affinity (approximately
      40% of the total antithrombin) had lost their inhibitory function. These inactive
      antithrombins were intact, monomeric, thermostable and resistant to unfolding in
      8 M urea. Moreover, the protein patterns on isoelectric focusing and non
      denaturing-PAGE showed that there were at least two different L-forms with
      isoelectric points separate from the native active species. Our findings
      demonstrate that approximately 40% of the antithrombin preparation examined
      exists as inactive L-forms. The clinical significance of administering this
      altered material is uncertain.

PMID- 9157591
TI  - Prevalence of factor V Leiden mutation in non-European populations.
AB  - A difference in the prevalence of venous thromboembolism (TE) in major human
      groups has been described and an uneven distribution of FV Leiden mutation over
      the world has recently been reported. We investigated FV Leiden mutation in 584
      apparently healthy subjects mostly from populations different from those
      previously investigated: 170 Europeans (Spanish, Italians), 101 sub-saharan
      Africans (Fon, Bariba, Berba, Dendi), 115 Asians (Indonesians, Chinese, Tharus),
      57 Amerindians (Cayapa), 84 Afroamericans (Rio Cayapa, Viche), and 57 Ethiopians
      (Amhara, Oromo). The mutation was detected in only 1/115 Asian (Tharu) and in
      5/170 Europeans (4 Italians, 1 Spanish). These data confirm that in non-Europeans
      the prevalence of FV mutation is at least 7 times lower than in Europeans and
      provide indirect evidence of a low prevalence not only of the FV Leiden gene but
      also of other genes leading to more severe thrombophilia. Finally, findings from
      the literature together with those pertaining to this study clearly show a marked
      heterogeneity among Europeans.

PMID- 9157592
TI  - Evaluation of original and modified APC-resistance tests in unselected
      outpatients with clinically suspected thrombosis and in healthy controls.
AB  - APC-resistance is the most common hereditary condition associated with venous
      thrombosis. It is in a majority of cases due to a single point mutation in the
      factor V gene (FVR506Q). Currently used functional APC-resistance tests have 85
      90% sensitivity and specificity for the FVR506Q mutation. A modified test which
      includes predilution of patient plasma in factor V depleted plasma has increased
      the sensitivity and specificity for the factor V mutation. However, neither the
      original nor the modified APC-resistance test have been evaluated in patients
      with acute thrombotic events. We have therefore used the original and the
      modified APC-resistance tests in 220 patients with clinically suspected acute
      deep venous thrombosis and in 278 healthy controls. The FVR506Q mutation was
      determined in all patients. The patients were classified as either DVT (deep
      venous thrombosis)-negative or DVT-positive depending on the outcome of contrast
      phlebography. In individuals with normal factor V genotype, the original APC
      resistance test gave significantly lower APC-ratio values both in DVT-positive
      and DVT-negative patients than in healthy controls. The specificity of the
      original APC-resistance test for the FVR506Q mutation in controls and in DVT
      negative and DVT-positive patients were 85%, 54% and 28%, respectively, when a
      cut off APC-ratio of 3.2 which insured 100% sensitivity was used. Using the
      modified APC-resistance test, essentially no difference in APC-ratios between
      patients with normal factor V genotype and healthy controls with normal factor V
      genotype was observed. The modified APC-resistance test had a specificity for the
      FVR506Q mutation of 98.8% at an APC-ratio cut off of 2.1 which ensured 100%
      sensitivity. The original APC-resistance test gave lower APC-ratios in women than
      in men and in patients with acute thrombosis as compared to controls. In
      conclusion, the modified APC-resistance test is highly sensitive and specific for
      the FVR506Q mutation. This test can be used in clinical practice as an easy to
      perform screening test for the FVR506Q allele. Moreover, the test performs
      equally well in patients with acute suspected venous thrombosis as in healthy
      controls.

PMID- 9157593
TI  - Evaluation of sensitivity and specificity of a standardized procedure using
      different reagents for the detection of lupus anticoagulants. The Working Group
      on Hemostasis of the Societe Francaise de Biologie Clinique and for the Groupe
      d'Etudes sur I'Hemostase et la Thrombose.
AB  - This study was designed to test the sensitivity and specificity of a combination
      of 3 phospholipid-dependent assays performed with various reagents, for the
      detection of lupus anticoagulant (LA). Plasmas containing an LA (n = 56) or
      displaying various confounding pathologies [58 intrinsic pathway factor
      deficiencies, 9 factor VIII inhibitors, 28 plasmas from patients treated with an
      oral anticoagulant (OAC)] were selected. In a first step, the efficiency of each
      assay and reagent was assessed using the Receiving Operating Characteristic (ROC)
      method. Optimal cut-offs providing both sensitivity and specificity > or = 80%
      were determined. The APTT assay and most of the phospholipid neutralization
      assays failed to discriminate factor VIII inhibitors from LA. In a second step,
      using the optimal cut-offs determined above, the results of all the possible
      combinations of the 3 assays performed with 4 different reagents were analyzed.
      Thirteen combinations of reagents allowed > or = 80% of plasmas of each category
      (LA, factor deficiency or OAC) to be correctly classified (3/3 positive test
      results in LA-containing plasmas and 0/3 positive results in LA-negative
      samples).

PMID- 9157594
TI  - Simultaneous occurrence of human antibodies directed against fibrinogen,
      thrombin, and factor V following exposure to bovine thrombin: effects on blood
      coagulation, protein C activation and platelet function.
AB  - We describe a patient with severe epistaxis, prolonged coagulation tests and
      decreased plasma factor V following exposure to bovine topical thrombin. Patient
      IgG, but not normal IgG, showed binding to immobilized thrombin (bovine > human)
      and fibrinogen, and to factor V by Western blotting; the binding to thrombin was
      inhibited by hirudin fragment 54-65. Electron microscopy of rotary shadowed
      preparations showed complexes with IgG molecules attached near the ends of
      trinodular fibrinogen molecules. Patient IgG inhibited procoagulant,
      anticoagulant and cell-stimulating functions of thrombin demonstrated by
      inhibition of fibrinogen clotting, protein C activation and platelet aggregation;
      thrombin hydrolysis of S-2238 was not inhibited. The results suggest that the
      antibody is targeted against anion-binding exosite and not catalytic site of
      thrombin. Antifibrinogen antibodies have not been reported in patients exposed to
      bovine thrombin. There is a pressing need to re-evaluate the role of bovine
      thrombin as a therapeutic agent.

PMID- 9157595
TI  - Expression and characterization of recombinant porcine plasminogen activator
      inhibitor-1.
AB  - Porcine models are, among other animal models, very suitable for in vivo
      investigations in the vascular field especially with respect to the possible
      relationship between atherosclerosis and thrombosis. In order to use this model
      to define the in vivo role of PAI-1, the characterization of porcine PAI-1 and
      its availability for the generation of immunological tools are a prerequisite.
      Porcine plasminogen activator inhibitor-1 (poPAI-1) cDNA was isolated from a cDNA
      library prepared from cultured porcine aortic cells and characterized in
      comparison with PAI-1 cDNA's from other species including human, bovine, rabbit,
      rat and murine. Subsequently the DNA sequence coding the mature protein was
      cloned into an appropriate vector for expression in Escherichia coli and
      recombinant porcine PAI-1 was purified and characterized. On SDS-PAGE the
      apparent molecular weight was estimated to be 45 kDa, identical to the molecular
      weight of human PAI-1. The purified recombinant porcine PAI-1 (rpoPAI-1) had a
      specific activity of 508,800 +/- 800 U/mg (mean +/- SD, n = 3) towards human
      tissue-type plasminogen activator (ht-PA) and a functional half-life in vitro of
      2.1 +/- 0.8 h (n = 3). Incubation with a two fold molar excess of ht-PA (n = 3)
      or human urokinase-type plasminogen activator (hu-PA, n = 2) followed by analysis
      by SDS-PAGE revealed reaction products corresponding to active (71 +/- 7% resp.
      96 +/- 3.6%), latent (12 +/- 0.4% resp. 2.6 +/- 2.4%) and substrate (16.6 +/-
      6.8% resp. 1.5 +/- 1.3) forms. Inactivated samples of porcine PAI-1 could be
      reactivated with guanidinium chloride up to 52% of its original specific activity
      towards t-PA and u-PA. The second order rate constant of inhibition of ht-PA was
      1.64 +/- 0.37 10(7)M-1 s-1 (n = 9). In gel filtration rpoPAI-1 in buffer eluted
      at a volume corresponding to 24 kDa, whereas in the presence of porcine plasma,
      the molecular form containing PAI-1 activity eluted at a volume corresponding to
      330 kDa, presumably as a consequence of binding of active PAI-1 to vitronectin.
      Taken together, these data demonstrate that no obvious functional differences
      exist between human and porcine PAI-1.

PMID- 9157596
TI  - PAI-1 concentrations in first-degree relatives of patients with non-insulin
      dependent diabetes: metabolic and genetic associations.
AB  - AIM: To identify whether levels of PAI-1 are elevated in relatives of NIDDM
      patients and the extent to which they relate to features of insulin resistance
      and to genotype at a common PAI-1 promoter polymorphism. RESULTS: In 132 first
      degree relatives of NIDDM patients and 151 controls PAI-1 activity was higher in
      relatives 14.4 U/ml than controls 9.3 U/ml (p < 0.0005) with higher body mass
      index 27.3 v. 24.7 kg/m2 p < 0.0005, fasting insulin 9.3 v. 7.6 mU/l p < 0.005
      and triglyceride 1.4 v. 1.2 mmol/l p < 0.05. PAI-1 activity levels were higher in
      men and in smokers and showed a trend to being higher with increasing number of
      4G alleles at the PAI-1 promoter polymorphism. After adjustment for age, sex,
      smoking, BMI and triglyceride levels, PAI-1 levels remained 26% higher in the
      NIDDM relatives (p = 0.01). CONCLUSION: In relatives of NIDDM patients PAI-1
      levels are elevated, presenting an additional mechanism for their increased
      cardiovascular risk.

PMID- 9157597
TI  - Plasminogen-dependent and -independent proteolytic activity of murine
      endothelioma cells with targeted inactivation of fibrinolytic genes.
AB  - Plasminogen-dependent and -independent proteolytic activity of marine
      endothelioma (End) cells that were derived from mice with targeted inactivation
      of the tissue-type plasminogen activator (t-PA-/-), urokinase-type plasminogen
      activator (u-PA-/-) or plasminogen activator inhibitor-1 (PAI-1-/-) genes was
      studied with the use of fibrin and extracellular matrix degradation assays. In a
      buffer milieu, the activation rate of plasminogen (final concentration 0.25
      microM) with wild-type and t-PA-/- End cells (3 x 10(4) to 4 x 10(6) cells/ml)
      was comparable, but it was about 4-fold reduced with u-PA-/- End cells and 3-fold
      enhanced with PAI-1-/- End cells. Plasminogen activation was markedly reduced by
      addition of amiloride or of anti-murine u-PA antibodies but not by addition of
      anti-murine t-PA antibodies, and it was not stimulated by addition of fibrin.
      Lysis of 125I-fibrin labeled matrix in the presence of plasminogen was comparable
      with wild-type, t-PA-/- and PAI-1-/- End cells (50% lysis in 3 h with 0.7 to 1.5
      x 10(6) cells/ml), but was significantly reduced with u-PA-/- End cells (50%
      lysis in 20 h with 0.87 x 10(6) cells/ml). Lysis of 3H-proline labeled
      extracellular matrix in the presence of plasminogen with wild-type, t-PA-/- and
      PAI-1-/- End cells (20% lysis in 48 h with 3 to 5 x 10(6) cells/ml) was
      comparable, but it was virtually abolished with u-PA-/- End cells. In the absence
      of plasminogen, lysis of both the fibrin and the extracellular matrix by all four
      cell types was drastically reduced and was virtually abolished by addition of
      phenylmethylsulfonylfluoride or 1,10 phenanthroline. These data indicate that the
      proteolytic activity of the transformed murine endothelioma cells, measured in
      plasminogen activation or matrix degradation assays, is essentially u-PA-related
      and largely plasminogen-dependent.

PMID- 9157598
TI  - Differential expression of low Mr GTP-binding proteins in human megakaryoblastic
      leukemia cell line, MEG-01, and their possible involvement in the differentiation
      process.
AB  - The expression of various low Mr GTP-binding proteins at various states of
      differentiation of a human megakaryoblastic leukemia cell line, MEG-01, was
      analyzed using thermocycle amplification of mRNA and immunoblotting. MEG-01 cells
      were found to express mRNAs of rap1A, rap1B, rap2B, ralA, rhoA, rac1, rac2,
      CDC42Hs, rab1, rab3B, rab6, ram and ran, but not rab4, and the proteins of Rap1,
      Rap2, RhoA, Rac1, Rac2, Rab3B, Rab4, Rab6 and Rab8 were expressed.
      Differentiation of MEG-01 cells induced by 100 nM 12-O-tetradecanoylphorbol-13
      acetate revealed the considerable increases in mRNA expression of rap1B, rab3B,
      rab4, ram and ran whereas the levels of rap2B, rhoA and rac1 decreased. During
      the differentiation process, significant changes in protein levels of Rap1, RhoA,
      Rac1, Rac2, Rab3B, Rab4 and Rab6 were observed among three subcellular (cytosol,
      Triton X-100-soluble membrane and -insoluble cytoskeleton) fractions. The present
      investigation may be useful for the study of the megakaryocyte differentiation.

PMID- 9157599
TI  - Enhanced increases in cytosolic Ca2+ in ADP-stimulated platelets from patients
      with delta-storage pool deficiency--a possible indicator of interactions between
      granule-bound ADP and the membrane ADP receptor.
AB  - The possible involvement of secreted platelet substances in agonist-induced
      [Ca2+]i increases was investigated by comparing these increases in aspirin
      treated, fura-2-loaded normal platelets and platelets from patients with storage
      pool deficiencies (SPD). In the presence and absence of extracellular calcium,
      the [Ca2+]i response induced by 10 microM ADP, but not those induced by 0.1
      unit/ml thrombin, 3.3 microM U46619, or 20 microM serotonin, was significantly
      greater in SPD platelets than in normal platelets, and was increased to the
      greatest extent in SPD patients with Hermansky-Pudlak syndrome (HPS), in whom the
      dense granule deficiencies are the most severe. Pre-incubation of SPD-HPS and
      normal platelets with 0.005-5 microM ADP produced a dose-dependent inhibition of
      the [Ca2+]i response induced by 10 microM ADP, but did not alter the [Ca2+]i
      increases induced by thrombin or U46619. Within a limited range of ADP
      concentrations, the dose-inhibition curve of the [Ca2+]i response to 10 microM
      ADP was significantly shifted to the right in SPD-HPS platelets, indicating that
      pre-incubation with greater amounts of ADP were required to achieve the same
      extent of inhibition as in normal platelets. These results are consistent with a
      hypothesis that the smaller ADP-induced [Ca2+]i increases seen in normal
      platelets may result from prior interactions of dense granule ADP, released via
      leakage or low levels of activation, with membrane ADP receptors, causing
      receptor desensitization. Addition of apyrase to platelet-rich plasma prior to
      fura-2 loading increased the ADP-induced [Ca2+]i response in both normal and SPD
      HPS platelets, suggesting that some release of ADP derived from both dense
      granule and non-granular sources occurs during in vitro fura-2 loading and
      platelet washing procedures. However, this [Ca2+]i response was also greater in
      SPD-HPS platelets when blood was collected with minimal manipulation directly
      into anticoagulant containing apyrase, raising the possibility that release of
      dense granule ADP resulting in receptor desensitization may also occur in vivo.
      Thus, in addition to enhancing platelet activation, dense granule ADP could also
      act to limit the ADP-mediated reactivity of platelets exposed in vivo to low
      levels of stimulation.

PMID- 9157600
TI  - Impaired prothrombin consumption in Bernard-Soulier syndrome is corrected in
      vitro by human factor VIII.
AB  - The Bernard-Soulier syndrome (BSS) is characterized by thrombocytopenia with
      giant platelets, a prolonged bleeding time with defective platelet adhesion to
      the subendothelium related to a defect in platelet membrane glycoprotein Ib
      (GPIb) and a decreased prothrombin consumption. The mechanism of the latter
      abnormality remains unknown. In this study, we showed that this defect was
      corrected by the addition of purified human factor VIII (FVIII) to blood from
      four patients with BSS. The correction of prothrombin consumption was almost
      complete at concentrations between 1.5 and 3 IU/ml of FVIII procoagulant activity
      (VIII:C) and partially abolished by a monoclonal antibody which neutralizes
      VIII:C. This correction was specific for FVIII and was not observed after
      addition of purified human FIX. It was obtained, in the same magnitude range,
      with FVIII complexed to von Willebrand factor (vWF) but not with free vWF. These
      data provide a new insight into the knowledge of the physiological interaction
      between the platelet membrane and the vWF-FVIII complex facilitating plasma
      coagulation activation and may lead to helpful therapeutic advances.

PMID- 9157601
TI  - Acute von Willebrand factor secretion from the endothelium in vivo: assessment
      through plasma propeptide (vWf:AgII) Levels.
AB  - Elevated plasma concentrations of von Willebrand factor (vWf) are increasingly
      recognized as a cardiovascular risk factor, and are used as a marker of
      endothelial activation. However, the factors which determine the rate of vWf
      release from the endothelium in vivo have not been defined clearly. In addition,
      vWf plasma levels may also be influenced by adhesion of vWf to the vascular wall
      or to platelets, and by its rate of degradation. The propeptide of vWf (also
      called vWf:AgII) is stored and released in equimolar amounts with vWf. In the
      present study we attempted to determine whether this propeptide could be a more
      reliable marker of endothelial secretion than vWf itself. To accomplish this we
      developed an ELISA based on monoclonal antibodies. The propeptide levels in
      normal plasma were found to be 0.7 microgram/ml, more than 10 times lower than
      vWf itself. Administration of desmopressin (DDAVP) induced a rapid relative
      increase in propeptide (from 106 to 879%) and in vWf (from 112 to 272%). However,
      the increases in vWf and propeptide were equivalent when expressed in molar
      units. A time course study indicated a half-life of the propeptide of 3 h or
      less. In a baboon model of disseminated intravascular coagulation (DIC) induced
      by FXa, vWf increased by less than 100%, whereas the propeptide concentrations
      increased by up to 450%. In view of the massive thrombin generation (as assessed
      by fibrinogen depletion), the increases in vWf are small, compared to the strong
      secretory response to thrombin and fibrin previously observed in vitro. Our
      results suggest that due to its rapid turnover, the propeptide could provide a
      sensitive plasma marker of acute endothelial secretion.

PMID- 9157602
TI  - C5a induces tissue factor activity on endothelial cells.
AB  - Tissue factor (TF) is an integral membrane glycoprotein that serves as a cofactor
      for blood coagulation factor VIIa. The induction of TF on the surface of
      endothelial cells is initiated by various stimuli including lipopolysaccharide,
      interleukin-1 beta, and tumor necrosis factor alpha. We have demonstrated that
      recombinant human C5a induces TF activity in a dose-dependent fashion in human
      umbilical vein endothelial cells (HUVEC). Peak activity (4.9-fold increase) was
      obtained 3-6 h after treatment with 10 microM C5a. TF mRNA as assessed by RT-PCR
      method was also significantly increased (3.75-fold) after 3 h incubation with
      C5a, suggesting that C5a induces TF activity on HUVEC, at least in part, by
      enhancing the level of TF mRNA. The increase in TF activity by C5a was inhibited
      by methylprednisolone. The induction of TF on endothelial cells by C5a may
      represent one of many potential interrelationships between the inflammatory and
      coagulation schemes.

PMID- 9157603
TI  - Antithrombin III-independent effect of depolymerized holothurian
      glycosaminoglycan (DHG) on acute thromboembolism in mice.
AB  - A previous study in this laboratory showed that depolymerized holothurian
      glycosaminoglycan (DHG) has two different antithrombin III (ATIII)-independent
      inhibitory effects on the in vitro blood coagulation system: heparin cofactor II
      (HCII)-dependent inhibition of thrombin, and ATIII- and HCII-independent
      inhibition of factor X activation by factor IXa-factor VIIIa complex (Nagase et
      al. Blood 85, 1527-1534, 1995). In the present study, we compared the
      antithrombotic effects of DHG in normal and in ATIII-deficient mice with those of
      unfractionated heparin (UFH) and low molecular weight heparin (LMWH). DHG, unlike
      UFH and LMWH, exerted an in vivo antithrombotic effect even in mice with
      decreased plasma ATIII activity (about 30% of normal). We then compared the
      anticoagulant and antithrombotic effects of DHG in mice with those of high
      molecular weight (HMW)-DHG, low molecular weight (LMW)-DHG, and dermatan sulfate
      (DS). In terms of in vitro anticoagulant activity assessed by use of purified
      human components, DHGs (DHG, HMW-DHG, and LMW-DHG) had different anti-thrombin
      activity in the presence of HCII and anti-factor Xase activities, which
      differences were dependent on the molecular weight. With respect to in vivo
      antithrombotic activity, DHG, HMW-DHG, and LMW-DHG showed almost the same
      inhibitory effect on acute thromboembolism in mice (minimum effective dose [MED]:
      > 0.3 mg/kg). Since the antithrombotic activities of DHGs were not correlated
      with the anticoagulant-specific activities, the contribution of the two
      anticoagulant activities to the in vivo antithrombotic effect of DHGs remains
      unknown. However, DHG was more effective against acute thromboembolism in mice
      than DS (MED > 1 or > 3 mg/kg), which showed no inhibitory activity toward factor
      Xase. Therefore, it seems that factor Xase inhibition contributes greatly to the
      antithrombotic effect of DHG and that DHG exerts this effect in mice mainly by
      inhibiting factor Xase.

PMID- 9157604
TI  - Antithrombin Morioka (Cys 95-Arg): a novel missense mutation causing type I
      antithrombin deficiency.

PMID- 9157605
TI  - The effects of age and menopause on erythrocyte aggregation.

PMID- 9157606
TI  - Impact of factor V Leiden mutation on duration of anticoagulation after a single
      thromboembolic event.

PMID- 9157607
TI  - In vivo modelling of coagulation factor concentrate thrombogenicity.

PMID- 9157608
TI  - Successful clinical use of a plasma-derived, dual virus inactivated factor VII
      concentrate incorporating solvent-detergent and dry heat treatment.

PMID- 9157609
TI  - [Milk production and freezing of milk samples].

PMID- 9157610
TI  - [Student and communication: veterinary practice week '97].

PMID- 9157611
TI  - [Burnout in veterinarians].

PMID- 9157612
TI  - [Performing of vaccination by 'either the veterinarian' or the stockbreeder].

PMID- 9157613
TI  - [Lameness in young dogs].

PMID- 9157614
TI  - [The forgotten animal and the one-man associate].

PMID- 9157615
TI  - [How to manage a rectal lesion in horses in clinical practice].
AB  - The most feared complication after a rectal examination of horses and ponies is
      to cause a tear of all the layers in the intraperitoneal part of the rectum. The
      description of the anatomy is an attempt to explain that the rectal tear is
      mostly located in the dorsal or dorsolateral part of the rectum. This article
      describes a relatively simple suture technique for the rectal tear by using the
      needle of Deschamp which is modified by Professor B. Huskamp. Furthermore there
      is a description of this method as treatment of two horses in practice
      circumstances. The issue whether causing a rectal tear should be regarded as a
      case of malpractice is discussed. Advises as prevention of rectal tears are
      given.

PMID- 9157616
TI  - [Vitamin E as a possible aid in the control of disease problems on pig farms: a
      field test].
AB  - In two sow-herds problems with weaning-diarrhoea and Streptococcus suis
      meningitis were successfully controlled by strategic use of antibiotics during
      the post-weaning period. In an attempt to reduce the intake of antibiotics by
      farm animals, the vitamin E level in the post-weaning diet was increased from 20
      IE/kg to 80 IE/kg, because vitamin E is thought to increase resistance. The
      effect on both farms was stunning, so a small field trial was started. In this
      trial the higher level of vitamin E had a statistically significant beneficial
      effect on weaning-diarrhoea. The author concludes that in some cases an increased
      level of vitamin E can have a positive effect on disease management on pig-farms
      and can lead to reduced use of antibiotics.

PMID- 9157617
TI  - [Medicine versus science of healing].

PMID- 9157618
TI  - [Assessment of the hygiene level of swine trucks after cleansing and after
      disinfection using 2 microbiological techniques. Hygiene of swine trucks improved
      in pilot project].
AB  - In a field study the hygiene level of trucks for the transport of pigs was
      measured. In total, on 56 times the hygiene level of a truck has been measured
      with two different methods, one microbiological method and one bioluminescence
      technique. During the field study 1.913 hygiene samples were taken. The average
      hygiene-level after cleaning and disinfection improved. The improvement was based
      on education and advisory about hygiene which immediately could be used by the
      truck-drivers. The fact that the results of hygiene measuring was shown directly
      was also a stimulation to the drivers; they improved their cleaning and
      disinfection job. The use of detergents by cleaning trucks is not required,
      although it contributes to a better hygiene-level. The introduction of plastic
      materials in stead of wood also improved the overall-hygiene in the
      transportation of animals.

PMID- 9157619
TI  - [Quackery or not, that is the question].

PMID- 9157620
TI  - [Rectal lesions in horses].

PMID- 9157621
TI  - ['Wild-West in Noord-Holland' or the curious case of cystitis in a cat].

PMID- 9157622
TI  - [Swine plague: symptoms, epizootiology and diagnosis].
AB  - The clinical signs, laboratory diagnosis and modes of transmission of classical
      swine fever are described. Special attention is paid to combinations of signs of
      disease which should arise suspicion to the veterinary practitioner in the
      present epizootic.

PMID- 9157623
TI  - [Electrotherapy or electrommythology? Possibilities and limitations of
      electrotherapy].
AB  - All of the established methods of electrotherapy are based on-at least-one of the
      following three scientifically and clinically confirmed working principles:
      electro-analgesia, muscle stimulation and tissue heating. The well defined
      indications for the different electrotherapeutical currents are inferred from
      these three principles, which are briefly described-together with their principal
      indications-in this contribution. At present some "complementary" forms of
      electrotherapy are being increasingly advocated. They are not clinically
      confirmed and, moreover, they lack a rationally founded working principle. These
      methods, so called "electromythology", are based on hypothetical and often
      clearly erroneous assumptions. Their therapeutic objective seems to be an
      unspecific stimulation of the cell metabolism, and their diagnostic goal is
      equally unspecific and universal. Frequently, these applications surmise an
      universal healing power inherent in the electric current as such. Because
      "electromythology" currently invades veterinary medicine, this contribution
      should help the reader to distinguish between realistic and excessive
      expectations.

PMID- 9157624
TI  - [Prehistoric fauna in Bulgaria].
AB  - Earliest husbandry in Bulgaria is investigated by the example of the Early
      Neolithic settlement of Koprivec. There was no domestication activity in the
      region. Pig-keeping was of no importance during the earliest period. Numerous
      bone-findings from the Aeneolithic up to the Bronze Age settlement of Durankulak
      build the base of a reconstruction of wildlife. Most of the larger mammals were
      species that lived in forests. Remarkable is the occurrence of the lion. A rich
      avifauna shows several species living near inland water or at the coast,
      different birds of prey as well as in the Aeneolithic layer bones of Otis tarda,
      which only occurs in the steppe. During the Bronze Age the spectrum of species
      has changed.

PMID- 9157625
TI  - [Case study. German spotted black cow, 4 years old].

PMID- 9157626
TI  - [Ethological, physiological and histological aspects of pain and stress in cattle
      when being dehorned].
AB  - The behaviour of 101 calves was evaluated during (n = 73) and after (n = 28)
      thermical dehorning without anaesthesia. Cortisol in saliva (n = 68) was measured
      in 68 calves. A simulation of dehorning was carried out as a control in most of
      the animals. The area around the horn bud was examined histologically in 20
      calves of different ages (newborn until 3-4 months old). Additionally, the
      influence of dehorning cows with a wire-saw under anaesthesia on behaviour (n =
      16), cortisol in saliva (n = 23), and the milk yield was examined. Independent of
      the calves' age, the horn bud and the surrounding hairy area were well
      innervated. For all calves dehorning without anaesthesia was a painful
      experience. During dehorning calves showed distinct pain and defense reactions.
      Most reactions were observed more often when the calves were dehorned as when
      dehorning was simulated. The cortisol in saliva was significantly increased after
      dehorning. In summary, we have to conclude that calves have a well developed
      nociceptive system from birth on. Therefore calves should only be dehorned using
      anaesthesia. Despite the anaesthesia, dehorning was stressful for the cows, as
      measured by a significant increase of cortisol in saliva. Moreover, cows showed
      pain reactions when the effects of the anaesthesia diminished. Dehorning had only
      a short effect on the milk yield of the cows.

PMID- 9157627
TI  - [Experimental studies of the effect of peracetic acid on the endometrium of
      cattle].
AB  - Histological investigations were made on uteri of 61 cattle (27 of them after
      intrauterine treatment). The response activated by 0.2% peracetic acid in the
      bovine endometrium was a primary inflammatory process, however, necrotising
      within clearly pronounced limits. Degenerative alterations were the major
      histological findings 35 minutes from application of 0.2% peracetic acid. They
      were recordable from the epithelium but at that point in time could easily affect
      the entire cellular stratum. Histopathological phenomena on the fourth day from
      application of 0.2% peracetic acid were clearly less strongly pronounced than on
      the third day. Histiocyte infiltrates of moderate and rarely high intensity
      reflected increased phagocytosis in the process of endometrial regeneration.

PMID- 9157628
TI  - [Teat endoscopy as a diagnostic procedure in the goat].
AB  - Teat endoscopy as a diagnostic procedure in the goat is described in a clinical
      case of a proliferation in the wall of the teat cisterna. Modifications in
      proceeding and equipment compared to the common use of endoscopy in the teat of
      cattle are shown and the additional amount of information in comparison to
      palpation, sounding and sonography is evaluated.

PMID- 9157629
TI  - [Physiology and physiopathology of ryanodine receptors in swine. Significance of
      sensitivity to stress, stress myopathies, malignant hyperthermia and meat
      quality].
AB  - During the last decades intensive breeding of pigs has improved the growth rate,
      food conversion and the ratio between meat and fat. However, this improvement is
      very often associated in certain breeds of pig with the porcine stress syndrome,
      a higher incidence of muscle diseases and a reduced meat quality referred to as
      pale, soft exudative pork (PSE). These problems are well known since decades and
      are obviously caused by a variety of factors. The discovery of a mutation in the
      ryanodine receptor or Ca-release channel in the striated muscles of affected pigs
      has concentrated research on the function of this protein. The mutation of the
      ryanodine receptor or Ca-release channel may account for the problems mentioned
      above because the changed ryanodine receptor can be activated much easier and
      there is no doubt that the inactivation is delayed or-under some circumstances
      even impossible. Consequently, the cytosolic Ca concentration in skeletal muscle
      cells will increase and induce uncontrolled muscle activity. The recommendation
      is given to breed out this mutation for elimination of a major reason of the
      porcine stress syndrome and PSE.

PMID- 9157630
TI  - [Circovirus infections in pigeons].
AB  - The first detection of circovirus infection in pigeons in Germany is described.
      The existing experiences with this still little known pigeon disease are
      summarized and similarities to circovirus infections in other species are shown.

PMID- 9157631
TI  - [Peritonitis in horses: a retrospective study of 95 cases].
AB  - Clinical signs of horses with peritonitis were colic (67.4%), elevated heart rate
      (53.2%), altered mucous membranes (75.8%), reduced intestinal motility (63.2%),
      increased tension of the abdominal wall (69.9%) and pyrexia (45.1%). The amount
      of obtained peritoneal fluid was increased in 62.3% of the horses. Colour and
      translucency of the peritoneal fluid were abnormal in 98.8% of the patients. The
      nucleated cell count was 83.5 (10-595) x 10(3)/microliter, protein content 35.6
      g/l (+/-14.2), specific gravity 1027.3 (+/-7.4) and the relative amount of
      neutrophils was 87.8% (+/-11). The physical examination and the examination of
      the peritoneal fluid were of diagnostic value. Complete blood count and blood
      chemistry indicated the degree of circulatory depression and the duration of the
      disease. Overall mortality was 47.4% (45/95). Non-survivors had significantly
      more often an increased heart- and respiratory rate, altered mucous membranes, an
      increased tension of the abdominal wall, reduced intestinal motility and
      increased amount of peritoneal fluid. Packed cell volume, urea, creatinine,
      glutamatdehydrogenase, sorbitoldehydrogenase, lactatdehydrogenase and blood pH
      were significantly different between survivors and non-survivors. All these
      parameters were statistically of no prognostic value.

PMID- 9157632
TI  - [Retinal and corneal dysplasias in the Yorkshire terrier and other dog breeds in
      Austria].
AB  - Mother and son of a Yorkshire Terrier family showed excessive multifocal retinal
      dysplasia (RD1) and geographical retinal dysplasia (RD2), intra- and preretinal
      hemorrhages partial and total retinal detachment (total RD/RD3), residues of the
      pupillary membrane and as a newness in this combination a geographical,
      subepithelial corneal opacity, composed of small dots. One, not examined son of
      the same litter was congenitally blind. Similar corneal opacities were also found
      in two Rough Collies affected with CEA, RD, and microphthalmia, a young German
      Wirehair Pointer with primary absolute glaucoma in conjunction with
      goniodysplasia and RD in the healthy seeming fellow eye as well as in a poodle
      puppy affected with bilateral posterior suture-line cataract in connection with
      persistent primary hyperplastic vitreous (PHPV) in one and a globe-shaped
      deformed retina in connection with a persistent, blood conducting hyaloid artery
      in the other eye. The latter finally resulted in intraocular hemorrhage and
      secondary glaucoma. A pathogenetic connection between ocular malformations and
      subepithelial corneal opacity seems to be likely.

PMID- 9157633
TI  - [Leishmaniasis in dogs in Germany: epidemiological case analysis and alternatives
      to conventional causal therapy].
AB  - Between January 1993 and September 1995 Leishmania infections were detected in
      236 dogs in Germany. Of the 132 epidemiologically evaluable dogs, 35 animals had
      travelled with their owners abroad in endemic areas and 97 dogs had been brought
      from these regions to Germany by animal lovers. As regards to the possible
      location of infection it has been registered that these dogs have been taken to
      countries of the Mediterranean Sea (Spain, France, Italy, Turkey) or to Portugal
      or had been imported from there. Therapeutic trials with allopurinol revealed
      that this drug administered at daily doses of 20 mg/kg bodyweight p.o. over weeks
      disposes of a sufficient therapeutic efficacy against canine leishmaniosis.

PMID- 9157634
TI  - [Reproductive physiology in New World camelids. Review].
AB  - Liamas and alpacas have gained international popularity over the last years.
      Therefore veterinarians are often asked to intervene in clinical management of
      different problems, especially reproductive problems. In this review the author
      attempts to summarize the material presented on the reproductive anatomy,
      physiology, behavior, embryo transfer and artificial insemination procedure of
      these animals.

PMID- 9157635
TI  - [Gait analysis in dogs].
AB  - Gait analysis has found extensive application in human medicine in orthopaedics,
      rehabilitation and sports medicine. In veterinary medicine locomotor studies are
      focused on horses. The available dynamometric and kinemetric measurement systems
      and their application to tetrapods are discussed after a historical survey with
      literary review has been made. The installation of a gait analysis laboratory for
      small animals at the Department of Veterinary Surgery of the Ludwig-Maximilians
      University of Munich and results of clinical studies including gait analysis will
      be presented.

PMID- 9157636
TI  - [Bile acid stimulation test with ceruletide].
AB  - The bile acid stimulation test is a sensitive and liver specific test to check
      liver function. In contrast to the postprandial estimation of serum bile acids
      which has been used up to now, it offers the advantage of a better
      standardization. Furthermore there are hardly any side effects. The test requires
      three blood samples at 0, 20, and 40 minutes after an i.m. injection of 0.3
      micrograms/kg KM Ceruletid (Takus). The normal values in the fasting state are
      under 5.0 mumol/l, 20 and 40 minutes after stimulation under 15.0 mumol/l serum
      bile acids.

PMID- 9157637
TI  - [Pathways and procedures of mycological diagnosis in veterinary laboratories. A
      diagnostic approach].
AB  - With the increasing fungal affections in humans and animals, the veterinary
      laboratories will have to reckon with more fungal specimens. A reliable and rapid
      identification of the etiologic agents will be required. The procedure with mould
      cultures is described in the general part. In the specific part, the general
      steps to differenciate medical important moulds (dermatophyes, zygomycetes,
      dematiaceous fungi, Aspergillus, etc.) are delineated. The identification of some
      fungal pathogens is possible by the means of the schematic representations.

PMID- 9157638
TI  - Papers presented at the 4th Summer School in Immunotoxicology. Aix-les-Bains,
      France, 18-20 October 1995.

PMID- 9157639
TI  - [The genetic transformation of Lycopersicon peruvianum var. dentatum by using
      Agrobacterium tumefaciens carrying a plasmid with the human beta-interferon
      gene].
AB  - Wild tomato plants of Lycopersicon peruvianum var. dentatum were transformed with
      pG11 plasmid having human beta-interferon (hIFN-beta) and NPTII genes.
      Transformation was demonstrated by polymerase chain reaction (PCR) and ELISA
      assay. Expression of hIFN-beta gene was identified by Western blot analysis.
      Transgenic plants produced seeds and F1 generation inherited integrated traits.

PMID- 9157640
TI  - [The bovine leukosis virus and the diagnosis of infected animals].
AB  - The results of selection of primers and amplification of fragments of provirus
      genes Gag and Env of bovine leukemia virus (BLV) in artificially infected cell
      line and in cattle leukocytes are presented. The distinctions between diagnoses
      of BLV infected animals by the testing their blood for antibodies to viral
      antigens and by the presence of provirus genes in DNA of their leukocytes were
      revealed.

PMID- 9157641
TI  - [A new system of prolonged genetic instability induced by N-ethyl-N-nitrosourea
      in Drosophila melanogaster].
AB  - A novel system of prolonged genetic instability induced by N-ethyl-N-nitrosourea
      in D. melanogaster was obtained. The instability was associated with the
      appearance of new mutations in loci yellow, scute, white, cut, singed, miniature,
      vermilion and extended for 40 generations. Some mutants of locus cut were
      obtained by the method of Southern blot-hybridisation. The reversion ct+ appeared
      as a result of excision of gypsy element. The mutation ctpN34 was localized in
      the second complementation group of cut locus and was the consequent of deletions
      of gypsy element and small DNA fragment and an insertion of a DNA sequence 7.8 kb
      in size.

PMID- 9157642
TI  - [The criterion of lactation stability in cows].
AB  - The stability of the lactation curves of high-productive cows (4000-9000 kg of
      milk per lactation period) was investigated. A new criterion of assessment of the
      lactation stability was proposed. Basic genetic criteria of the index of
      lactation stability (coefficients inheritance and reiteration) were responded.

PMID- 9157643
TI  - [MtDNA-like sequences and the coordination of the functioning of mammalian
      nuclear and mitochondrial genomes].
AB  - Mitochondrial DNA-like sequences in the nuclear genome of mammals are classified
      in two types: ontogenetic and evolutionary. Mechanisms of the transfer of DNA
      from mitochondria into nucleus and transformation of the ontogenetic mtDNA-like
      sequences to evolutionary ones are discussed. The origin of short sequences of
      DNA common to nuclear and mitochondrial genome and the role of these sequences in
      the coordination of gene expression have received much attention.

PMID- 9157645
TI  - Feline urodynamic procedures.
AB  - Urodynamic procedures are those studies which investigate the process of storage
      and evacuation of urine in the lower urinary tract, usually by recording pressure
      or flow characteristics in the urinary bladder or urethra. Cystometric
      techniques, urethral pressure profilometry, electromyography, and evoked
      potentials have been adapted for use in cats. The applications and limitations of
      each of these techniques are discussed.

PMID- 9157644
TI  - [The use of an automated micronucleus test for the biological dosimetry of
      radiation lesions].

PMID- 9157646
TI  - Urethroscopy, cystoscopy, and biopsy of the feline lower urinary tract.
AB  - This article discusses the utility and limitations of urethroscopy and cystoscopy
      in both male and female cats. The special equipment and techniques necessary to
      adequately visualize the urethra and bladder of female cats are described in some
      detail. The emerging ability to visualize the male urethra is introduced.
      Photographs taken through the cystoscope are used to illustrate both normal
      anatomy and lesions likely to be encountered with cats with lower urinary tract
      disease. Cystoscopy is an important diagnostic tool for an inclusionary and
      exclusionary diagnosis of interstitial cystitis (sterile idiopathic
      inflammation).

PMID- 9157647
TI  - Cystoscopy and biopsy of the feline lower urinary tract.
AB  - Cystoscopy is rapidly developing as a diagnostic and therapeutic technique for
      application in feline practice. Instruments are currently available that provide
      transurethral access to the lower urinary tract in most cats with prepubic
      percutaneous cystoscopy allowing evaluation when transurethral cystoscopy is not
      applicable. Cystoscopy is indicated for assessment of chronic cystitis,
      hematuria, tenesmus, increased frequency of urination, urinary incontinence,
      alteration of urinary stream, trauma, and cystic and urethral calculi. The
      vagina, urethral opening, urethra, bladder, and ureteral openings can be
      effectively assessed and samples can be collected for histopathology, cultures,
      and stone analysis. Cystoscopy provides easy access to diagnostic information
      that can be difficult to obtain with any other technique.

PMID- 9157648
TI  - Medical management of feline urethral obstruction.
AB  - A step-by-step priority of procedures is recommended when attempting to restore
      urethral patency in an obstructed male cat. In order of priority they are: (1)
      massage of the distal urethra, (2) attempts to induce voiding by gentle palpation
      of the urinary bladder, (3) cystocentesis, (4) retrograde urethral flushing, (5)
      combinations of 1 through 4, (6) diagnostic radiology to determine if the cause
      of urethral obstruction is intraluminal, mural or extramural, and if absolutely
      necessary, (7) surgical procedures.

PMID- 9157649
TI  - Use and misuse of indwelling urethral catheters.
AB  - Because indwelling urethral catheterization is potentially detrimental,
      especially when it leads to urinary tract infection, indwelling urinary catheters
      must not be used indiscriminately. Appropriate use of indwelling catheters in
      recently obstructed cats is accomplished by identifying which cats are likely to
      experience repeated obstruction if such catheterization is not performed. When
      indwelling catheters are used, precautions must be taken to minimize the
      occurrence and severity of catheter-associated complications. Following catheter
      removal, which should be done as soon as possible, urine culture results should
      be used to verify absence of infection or to guide treatment when infection is
      detected.

PMID- 9157650
TI  - Management of postrenal azotemia.
AB  - Postrenal azotemia is a potentially life-threatening consequence of urinary
      obstruction Its most serious consequences include fluid volume deficits,
      hyperkalemia, and metabolic acidosis. Immediate therapy should be directed at
      restoring urine flow, correcting extracellular fluid volume deficits, minimizing
      the cardiac toxicity of hyperkalemia, and ameliorating the cardiovascular effects
      of metabolic acidosis. Most patients respond quickly and completely to such
      therapeutic intervention.

PMID- 9157651
TI  - Pharmacologic management of feline lower urinary tract disorders.
AB  - Pharmacological recommendations for the treatment of lower urinary tract
      disorders in cats are rapidly evolving as more is learned about the physiology
      and pathophysiology of the feline urinary bladder and urethra. Recent
      investigations and clinical observations have led to reconsideration of
      previously prescribed treatments and to the use of new and alternative
      pharmacologic agents. Pharmacologic agents used in the management of common lower
      urinary tract disorders in cats, including urinary tract infections, idiopathic
      lower urinary tract inflammation, urinary incontinence, urine retention, and
      urinary elimination disorders, are reviewed.

PMID- 9157652
TI  - Feline perineal urethrostomy: a potential cause of feline lower urinary tract
      disease.
AB  - Perineal urethrostomies are associated with complications that may mimic primary
      causes of feline lower urinary tract disorders. Though postoperative urethral
      strictures may be minimized by proficiency with an effective surgical technique,
      removal of the distal urethra may result in bacterial urinary tract infections in
      25% to 30% of patients after surgery. Urinary tract infections caused by urease
      producing microbes may induce struvite urolith formation. Thus the prophylactic
      benefits of minimizing recurrent urethral obstruction by urethrostomy must be
      weighed against a long-term predisposition to recurrent bacterial urinary tract
      infection and urolith formation.

PMID- 9157653
TI  - Medical management of iatrogenic rents in the wall of the feline urinary bladder.
AB  - Surgical closure may not be necessary to successfully manage all patients with
      ruptured urinary bladders. If the margins of the walls of tears in the bladder
      wall are not devitalized, and if they remain in close apposition via maintenance
      of the bladder lumen in a nondistended state for an appropriate period, these
      conditions may simulate those created by use of surgical sutures. This is not
      advocating an all-or-none choice. Because the clinical status of patients with
      ruptured urinary bladders can range from that characterized by only hematuria and
      dysuria to life-threatening postrenal uremia, a range of surgical and medical
      options should be considered.

PMID- 9157654
TI  - Prednisolone therapy of idiopathic feline lower urinary tract disease: a double
      blind clinical study.
AB  - A double-blind clinical study was performed to evaluate prednisolone as treatment
      for idiopathic feline lower urinary tract disease. No differences in response
      were observed in prednisolone- and placebo-treated cats.

PMID- 9157655
TI  - Management of nonobstructive idiopathic feline lower urinary tract disease.
AB  - Consistently effective treatment and prevention of nonobstructive idiopathic
      lower urinary tract disease (LUTD) in male and female cats remains an enigma.
      Because clinical signs associated with this form are frequently self-limiting,
      considerable debate exists about the efficacy of various symptomatic therapies
      advocated for management of idiopathic feline LUTD. Any form of therapy might
      appear to be beneficial, as long as it was not harmful. The self-limiting nature
      of some forms of idiopathic feline LUTD underscores the need for controlled
      prospective double-blind clinical studies to prove the value of various forms of
      therapy.

PMID- 9157656
TI  - Diagnosis, medical treatment, and prognosis of feline urolithiasis.
AB  - Radiographic or ultrasonographic evaluation of the urinary tract is required to
      consistently detect feline uroliths. Evaluation of clinical, laboratory, and
      radiographic findings facilitate "guesstimation" of the mineral composition of
      uroliths. Therapy should not be initiated before appropriate samples have been
      collected for diagnosis. The objectives of medical management of uroliths are to
      arrest further growth and to promote urolith dissolution by correcting or
      controlling underlying abnormalities. For therapy to be effective, it must induce
      undersaturation of urine with calculogenic crystalloids by (1) increasing the
      solubility of crystalloids in urine, (2) increasing the volume of urine in which
      crystalloids are dissolved or suspended, and (3) reducing the quantity of
      calculogenic crystalloids in urine.

PMID- 9157657
TI  - Management of urocystoliths by voiding urohydropropulsion.
AB  - Voiding urohydropropulsion is a nonsurgical method of removing uroliths from the
      urinary bladder. Any urocystolith of sufficient size to pass through the
      distended urethral lumen can be safely and effectively removed by this new
      technique. Compared to cystotomy, voiding urohydropropulsion offers several
      advantages: urolith removal can be performed in minutes, anesthetic period is
      shorter, postprocedural dysuria and hematuria are less severe, and it provides
      greater success for complete removal of small urocystoliths. This technique is
      not suitable for removal of large urocystoliths or uroliths that become lodged in
      the urethral lumen.

PMID- 9157659
TI  - Management of feline lower urinary tract disease by homeopathy.
AB  - Homeopathy is a system of therapeutics based on a philosophy of treating various
      disease symptoms with minute quantities of natural drugs capable of producing
      comparable symptoms if given in large doses to healthy patients. Suitable studies
      have not been performed to substantiate the claim that they have any beneficial
      effect in cats with lower urinary tract disease.

PMID- 9157658
TI  - Treatment of feline lower urinary tract disease by debriding the bladder mucosa:
      first do no harm.
AB  - Based on current knowledge and understanding about the cases and biologic
      behavior of feline lower urinary tract diseases, debridement of the bladder
      mucosa is likely to increase rather than decrease the morbidity associated with
      these diseases. It is not recommended.

PMID- 9157660
TI  - Behavioral and pharmacologic approaches to problem urination in cats.
AB  - Problem urination is the most frequent feline behavior problem for which
      veterinary consultation is sought. The first step is to differentiate between
      inappropriate urination and urine marking. This is an array of behavioral
      approaches that are particularly useful with inappropriate urination and may also
      be useful with urine marking. Anti-anxiety drugs may be used if behavioral
      approaches are not effective in treating urine marking or inappropriate
      urination.

PMID- 9157661
TI  - [Computed tomography of the pleura].
AB  - The paper examines CT images of the pleura and interlobar culci in health and in
      disease. For this, 403 patients were examined (420 CT studies), of whom 218 had
      pleural lesion and 185 formed a control group. The complex of studies involved
      computed tomography (CT) as compared with conventional radiation studies. The CT
      symptomatology of free and sacculated exudates, empyemas of the pleura, pleural
      depositions and adhesions, tumor lesions of the pleura. Based on the findings, an
      original scheme of free and sacculated pleural exudates was offered in CT images.
      The findings have led the authors to the conclusion that computed tomography is a
      more sensitive method in the evaluation of the pleura than standard X-ray study.

PMID- 9157662
TI  - [Radiographic differential diagnosis of surgical diseases of the lungs:
      diagnostic errors and their causes].
AB  - This study examines the reasons for complete divergences between the results of
      complex radiation study and the morphological verification of a diagnosis. A
      hundred and fifty cases with peripheral and central diseases of the lung were
      examined. There were 16 (10.7%) divergences of CT and X-ray conclusions with the
      histological verification of a diagnosis. The reasons of errors of complex
      radiation diagnosis were due both to the same type of symptoms, their latency and
      subjective ideas when the symptoms were analyzed. The greatest differentially
      diagnostic difficulties arose when peripheral formations were estimated.

PMID- 9157663
TI  - [X-ray longitudinal and computed tomography in the diagnosis of peripheral tumor
      like formations of the lungs].
AB  - Fifty eight patients with peripheral tumor-like formations of the lung (33 with
      cancer and 25 with benign formations) were examined by longitudinal tomography
      and CT. The potentialities of the two techniques in detecting the major semeiotic
      signs of cancer and malignant formations were compared. The main or major signs,
      such as the shape of shadow and the pattern of outlines, which make it possible
      to differentiate benign and malignant formations, are virtually equally imaged by
      the two techniques. CT is superior to X-ray longitudinal tomography in revealing
      minor calcifications and microdestructions, hyperplastic intrathoracic lymph
      nodes. The significance of some symptoms for differential diagnosis calls for
      further clarification.

PMID- 9157664
TI  - [Puncture methods of the diagnosis and treatment under the control of US, CT and
      X-ray video image].
AB  - Exploratory and therapeutical punctures were made in 454 patients under the
      control of ultrasound, CT, and X-ray teleimage. Diagnostic biopsies established
      the cytological and histological nature of diseases in 67.6% of cases, positive
      ultrasound-, CT-, and X-ray teleimage-controlled biopsies being 76.3, 64.9, and
      71.4%, respectively. Beneficial effects of therapeutical interventions were
      obtained in 89.5% of patients.

PMID- 9157665
TI  - [X-ray endovascular dilatation of coronary arteries in patients with unstable
      angina pectoris].
AB  - The outcomes of X-ray endovascular dilatation of coronary arteries in 46 patients
      with unstable angina pectoris are presented. Angioplasty proved to be
      angiographical-ly effective in 15 cases, anginal episodes ceased in 13. In 5
      patients, successful dilatation was accompanied by coronary intimal dissection,
      as evidenced by angiography; however, its clinical effect was good. Low incidence
      rates of complications was likely to be associated with the relative
      normalization of the patients' condition during intensive drug therapy.

PMID- 9157666
TI  - [Study of immunological parameters in radiography and excretory urography].
AB  - Some immunological parameters (levels of serum complement, content of circulating
      immune complexes, and serum concentrations of immunoglobulins) were examined in
      patients after excretory urography by using triombrast and after X-ray studies
      without applying any contrast substance. Some changes were found in the activity
      of complement and in the concentration of immunoglobulins following intravenous
      triombrast injection. In addition, the above parameters were evaluated in
      patients with adverse reactions during the contrast study. The findings are
      discussed in terms of the immunotropic effects of triombrast.

PMID- 9157667
TI  - [A case of peripheral cancer of the lung].

PMID- 9157668
TI  - [Value of computed tomography in the differential diagnosis of infiltrative
      changes in the lungs].
AB  - Computed tomography (CT) was performed in 73 patients with pulmonary infiltrative
      changes of unknown etiology. Their preliminary clinical and X-ray studies
      suggested protracted pneumonia in 46.6%, malignant neoplasms in 27.4%,
      tuberculosis in 16.1%, and pyesis in 9.9%. The preliminary clinical and X-ray
      conclusion fully agreed with the verified diagnosis only in 31.5% of patients.
      The accuracy of CT in assessing infiltrative changes was much higher and ran to
      89.1%. According to CT findings, nontumor diseases were found in 56 (76.7%)
      patients, malignant tumors in 17 (23.3%). Among inflammatory processes there were
      prevalent pyesis 23.3%), pulmonary tuberculosis (20.7%) and pneumonias (19.2%).
      In the group of 17 patients with neoplasms, 8 were found to have central cancer
      with hypoventilation of a lung portion, 4 had peripheral cancer, and 5 presented
      with bronchoalveolar carcinoma. The use of high-performance CT is of great
      importance.

PMID- 9157669
TI  - [Disseminated pulmonary process developing in concurrent diseases and their
      multimodal treatment].

PMID- 9157670
TI  - [Storing of x-ray information].

PMID- 9157671
TI  - [Optimization of methodological approaches in computed x-ray studies using Picker
      devices].

PMID- 9157672
TI  - [Comparative intravascular use of various iodine-containing contrast media].

PMID- 9157673
TI  - [Magnetic resonance tomography and magnetic resonance angiography in the imaging
      of vascular structures].

PMID- 9157674
TI  - [Iodixanol: a new nonionic dimeric contrast medium for angio-cardiography
      urography].

PMID- 9157675
TI  - The pathogenesis of necrotic proliferative colitis in swine is linked to whipworm
      induced suppression of mucosal immunity to resident bacteria.
AB  - Mucohemorrhagic enteritis syndrome in swine has a complex etiology with largely
      unknown pathogenesis. We have observed that inoculation of pigs with swine
      whipworm, Trichuris suis, initiates an interaction with resident bacterial flora
      to induce mucohemorrhagic enteritis. The role of bacteria in this mixed infection
      was demonstrated using 4 treatment groups. One group of pigs was inoculated with
      2500 embryonated T. suis eggs alone, while a second group received T. suis eggs
      along with broad spectrum antibiotic treatment. Two other control groups of pigs
      were uninoculated and were either treated with antibiotic or untreated. Pigs
      inoculated with T. suis eggs exhibited diarrhea, mucosal edema, inflammatory cell
      infiltration, bacterial accumulation at the site of worm attachment in the
      proximal colon, and intestinal adenomatosis associated with the intracellular
      Ileal symbiont intracellularis bacteria. In addition, enlarged lymphoglandular
      complexes (LGCs) containing numerous extracellular bacteria, eosinophils,
      lymphocytes, macrophages, and neutrophils were observed in the distal colon. The
      other group of pigs that was inoculated with T. suis but treated with antibiotics
      had lesions localized to the site of worm attachment and histologically normal
      LGCs with no invasive bacteria in the distal colon. The groups of uninoculated
      pigs, with or without antibiotic treatment, exhibited no pathology or bacterial
      invasion. It appears that the complex pathogenesis of necrotic proliferative
      colitis in pigs may be linked to worm induced suppression of mucosal immunity to
      resident bacteria. Further, the association between bacteria,lymphocytes and
      macrophages in the LGCs of pigs infected with T. suis suggests an antigen
      processing role for these structures in the colon. Further, the complex
      pathogenesis of necrotic proliferative colitis in pigs may be linked to worm
      induced suppression of mucosal immunity to resident bacteria.

PMID- 9157676
TI  - Development of a sandwich ELISA for ovine granulocyte/macrophage colony
      stimulating factor.
AB  - Recombinant ovine granulocyte/macrophage colony-stimulating factor (rOv GM-CSF)
      has been expressed in Chinese hamster ovary cells. A stable, cloned line of these
      cells has been established which secretes high levels (40 mu g ml(-1)) of rOv GM
      CSF. Three murine monoclonal antibodies (mAbs) were produced which reacted with
      rOv GM-CSF on Western blots. These mAbs also neutralised the activity of both
      recombinant and native Ov GM-CSF in a bone marrow haemopoietic progenitor cell
      assay. Two of the mAbs, which recognise mutually exclusive epitopes, were
      selected for the development of a sandwich enzyme-linked immunosorbent assay
      (ELISA) to measure GM-CSF in biological samples of ovine origin.

PMID- 9157677
TI  - Immune functions in beluga whales (Delphinapterus leucas): evaluation of mitogen
      induced blastic transformation of lymphocytes from peripheral blood, spleen and
      thymus.
AB  - A quantitative assay was developed to evaluate mitogen-induced lymphoblastic
      transformation in beluga whales (Delphinapterus leucas) using peripheral blood
      mononuclear cells, splenocytes and thymocytes. Optimal concentrations of four
      different mitogens (Con-A, PHA, LPS and PWM) were determined with the use of
      standard curves. Addition of human recombinant IL-2 (rhIL-2) after 48 h in
      culture with the different mitogens suggests that Con-A, PHA and PWM, but not
      LPS, stimulate T cells in belugas, as they do in other animal species. The
      addition of 2-mercaptoethanol did not enhance significantly the proliferation of
      cells stimulated by Con-A, PHA and LPS, while it did with the cells stimulated by
      PWM and those cultured without mitogen. The proliferative response of cells was
      suppressed when the culture medium was supplemented by beluga serum instead of
      fetal calf serum. This assay will be useful to assess the status of the immune
      functions in different populations of beluga whales as well for further in vitro
      immunotoxicological experiments.

PMID- 9157678
TI  - Low calcium diet and 1,25-dihydroxyvitamin D(3) infusion modulate immune
      responses during Mycobacterium paratuberculosis infection in beige mice.
AB  - A 12-month study was conducted to evaluate the effects of feeding a low calcium
      (Ca) diet or 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3) infusion on the
      persistence of Mycobacterium paratuberculosis infection using a mouse model. Male
      beige mice 6-8 weeks of age were assigned to one of the following treatments: (1)
      non-infected, (2) infected,(3) non-infected/1,25(OH)(2)D(3), (4)
      infected/1,25(OH)(2)D(3), and (5) infected/low Ca (0.15 percent) diet. Infected
      mice were inoculated intravenously with live M. paratuberculosis. At 1, 6 and 12
      months postinfection, mice in Treatments 3 and 4 were implanted subcutaneously
      with mini-osmotic pumps to deliver 1,25(OH)(2)D(3). Infusion with 1,25(OH)(2)D(3)
      exacerbated M. paratuberculosis infection in most tissues at all time points.
      Mice infused with 1,25(OH)(2)D(3) had higher bacterial counts in spleen, liver,
      and ileum compared with control infected mice after 1 month of infection. In
      contrast, feeding a low Ca diet reduced the number of viable organisms cultured
      from the liver and ileum of infected mice. Plasma Ca and 1,25(OH)(2)D(3) were
      increased in mice infused with 1,25(OH)(2)D(3) at all time points but values for
      low Ca mice were not different than for non-infused mice. Splenocyte production
      of TNF, IL-1 and IL-6 was higher for mice fed the low Ca diet compared with
      control infected mice after 1 month of infection. Inducible IL-6 activity
      remained higher for this treatment at 6 months postinfection. These results
      suggest that feeding a low Ca diet to mice chronically infected with M.
      paratuberculosis appears to enhance their ability to clear the infection in a
      manner distinct from any effect of 1,25(OH)2D3.

PMID- 9157679
TI  - Offspring of xenogeneically-reconstituted scid/scid mice are capable of a primary
      xenogeneic immune response to DNP-KLH.
AB  - Human peripheral blood leukocyte (PBL) reconstitution of severe combined
      immunodeficient (SCID) mice has provided a small animal model system (hu-PBL
      SCID) useful for the study of the human immune system and disease pathogenesis.
      Transfer of xenogeneic PBL from donors other than humans has also been
      successful; however, the controversy remains regarding the capability of
      xenogeneically engrafted lymphocytes to mount a primary immune response. Human
      cells have been identified in offspring from hu-PBL-SCID but were not evaluated
      for a primary immune response. In the present study, offspring of bovine PBL
      reconstituted SCID mice (F1-PBL-SCID-bo) were assessed for specific immune
      function. Sera from all of the F1-PBL-SCID-bo contained relatively low levels of
      bovine IgG 5 weeks after birth but bovine Ig became undetectable by 14 or 18
      weeks. Eight F1-PBL-SCID-bo (23 or 27 weeks of age) were immunized with a single
      dose of 100 mu g dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH). Individual
      cells secreting bovine antibody were enumerated using the ELISA-plaque assay. One
      week after immunization, bovine cells secreting bovine immunoglobulin (IgG)
      specific for DNP-KLH were identified in the spleens from three of the F1-PBL-SCID
      bo at a frequency of one antibody-secreting cell per 9 x 10(3) to 1 x 10(6)
      spleen cells. Thus, xenogeneic lymphocytes, passed from the mother to her
      offspring, retain the capacity for a primary immune response to DNP-KLH.

PMID- 9157680
TI  - The effect of temperature and water quality on antibody response to Aeromonas
      salmonicida in sunshine bass (Morone chrysops x Morone saxatilis).
AB  - The kinetics of the antibody response to Aeromonas salmonicida were determined in
      sunshine bass (hybrid striped bass: female Morone chrysops X male Morone
      saxatilis) acclimated to 10, 18, 24, 29 degrees C, and to 0.15 mg 1(-1) un
      ionized ammonia and 200 mg 1(-1) nitrate levels. Temperature and water quality
      factors affected the immune response of sunshine bass. Temperatures of 10 degrees
      C and 18 degrees C decreased the magnitude and delayed the time of the antibody
      response to A. salmonicida. The antibody response was not affected at 29 degrees
      C, which is above the optimal temperature for sunshine bass. Elevated un-ionized
      ammonia concentrations of 0.15 mg 1(-1) also did not affect the antibody
      response. Elevated nitrate levels of 200 mg 1(-1), however, decreased the
      antibody response to the same extent as 18 degrees C water.

PMID- 9157681
TI  - Reduced expression of SLA Class 1 antigens by intestinal epithelium of newborn
      piglets.
AB  - Expression of major histocompatibility complex Class 1 by the small intestine
      mucosa of piglets was compared by indirect immunofluorescence during the 4 days
      following birth with both maternal and artificial feeding. The duodenal
      epithelium did not express Class I antigen during these 4 days. The jejunal
      epithelium did not express Class I antigen at Day 0 after birth but expression
      developed from Day 1. However ileal epithelium expressed Class 1 antigen
      throughout the study period. In contrast, cells from the lamina propria of all
      samples expressed Class 1 antigen. There was no difference between piglets
      receiving maternal colostrum and artificially reared piglets. This lack of Class
      1 expression occurs at a time when the intestinal epithelium constitutes an
      interface between piglet and colostral maternal cells. This can be of biological
      relevance for mother-newborn interactions.

PMID- 9157682
TI  - Altered expression of class I major histocompatibility antigens on bovine cells
      infected with the protozoan parasite Theileria annulata.
AB  - Theileria annulata infection is controlled by MHC class I restricted cytotoxic T
      cell killing of infected cells. The long term persistence of parasite suggests
      that it employs a mechanism to avoid immune surveillance. In this paper we
      describe the modification of BoLA class I antigens on the surface of Theileria
      annulata transformed lymphoblastoid cells. The extent of modification is
      different between individuals varying from extensive to undetectable.

PMID- 9157683
TI  - Changes of lymphocyte subpopulations in pigs infected with porcine reproductive
      and respiratory syndrome (PRRS) virus.
AB  - Abnormal changes of T-cell subpopulation were observed in the peripheral blood
      lymphocytes of pigs infected with porcine reproductive and respiratory syndrome
      (PRRS) virus. Pigs with naturally occurring PRRS revealed increases in CD2+ and
      CD8+ cells, and decreases in CD4+ cells and the ratios of CD4+/CD8+ cells.
      Specific-pathogen-free pigs inoculated with PRRS virus showed remarkable
      decreases in total lymphocytes, CD4+ and CD2+ cells on Postinoculation Day (PID)
      3. The decline of CD4+ cells continued for at least 14 days, while CD2+ cells
      showed a tendency to increase thereafter. On the other hand,CD8+ cells slightly
      decreased in number on PID 3, and then increased remarkably; their number was
      significantly larger on PIDs 28 and 35 than on PID 0. The ratios of CD4+/CD8+
      cells were significantly low between PIDs 3 and 28 as compared with PID 0.
      However, there were no differences in thymocyte subpopulations between infected
      and non-infected pigs, suggesting that the PRRS virus does not modulate
      intrathymic T-cell differentiation. In an experiment with peripheral blood
      mononuclear cell cultures, PRRS virus caused neither alteration of T-cell
      subpopulations nor cell proliferation, suggesting that the virus is not cytotoxic
      for CD4+ cells and not mitogenic for CD8+ cells.

PMID- 9157685
TI  - Evidence for genetic control of vaccine-induced antibody responses in cattle.
AB  - The purpose of our study was to identify evidence for genetic control of immune
      responses in cattle. To address this question, we evaluated the variation of
      antibody responses induced by vaccination with Brucella abortus Strain 19, a live
      attenuated bacterial vaccine, in large half-sibling families. The data were
      analyzed using a parametric statistical model that incorporated the effects of
      sire, bovine major histocompatibility complex (BoLA) types and parameters related
      to the experimental design. The BoLA types represented a readily identifiable
      marker, analogous to those known to be associated with genetic control of immune
      responses in other mammals. Variation between individual animals within our test
      population was significant but we were able to identify both individual animals
      and families with high or low antibody production phenotypes. In several cases,
      these traits were significantly correlated with individual bulls, suggesting the
      existence of sire effects, or with individual BoLA types. These findings are
      consistent with the theory that at least two separate genes or genetic systems
      contribute to the control of bovine antibody responses to B. abortus vaccination.
      These genetic effects are likely to be analogous to those identified in several
      species of laboratory rodents and humans.

PMID- 9157684
TI  - Regulation of luminol-dependent chemiluminescence and degranulation by bovine
      neutrophils stimulated with opsonized zymosan.
AB  - The purpose of this study was to elucidate likely signal transduction pathways in
      activated bovine neutrophils, by comparing the effects of various inhibitors on
      the bovine neutrophil respiratory burst and degranulation in vitro. The protein
      kinase C(PKC) inhibitors staurosporine, and chelerythine, and the beta-adrenergic
      receptor antagonist DL-propranolol, markedly inhibited opsonized zymosan (OZ)
      stimulated luminol-dependent chemiluminescence (LDCL). The G-protein inhibitor
      pertussis toxin (PT), the protein tyrosine inhibitor genistein, and the calcium
      channel blocker verapamil also reduced LDCL in a dose-dependent manner. In
      contrast, the lipoxygenase inhibitor zileuton had only a slight effect, and the
      cyclooxygenase inhibitor indomethacin had no effect on LDCL. The effects of these
      inhibitors on degranulation was also examined. Staurosporine, propranolol, and
      pertussis toxin significantly decreased primary granule (beta-glucosaminidase)
      release in response to OZ. These inhibitors also significantly reduced both
      phorbol myristate acetate (PMA)-induced primary and secondary granule
      (lactoferrin) release. Regulation of secondary granule (lactoferrin) release was
      complex, as it was significantly depressed by propranolol, enhanced by PT and
      unaffected by staurosporine. These findings suggest that PKC, beta-adrenergic
      receptors, G-proteins, protein tyrosine kinase(s) and Ca(2+) uptake, may all be
      involved in some part of the process of bovine neutrophil activation. Moreover,
      stimulation of LDCL and degranulation may be mediated through distinct signal
      transduction pathways.

PMID- 9157686
TI  - Intracellular survival of Brucella abortus, Mycobacterium bovis BCG, Salmonella
      dublin, and Salmonella typhimurium in macrophages from cattle genetically
      resistant to Brucella abortus.
AB  - Peripheral blood monocyte-derived macrophages were obtained from a herd of cows
      selected, bred, and confirmed as resistant or susceptible by in vivo challenge of
      Brucella abortus Strain 2308. The ability to control in vitro intracellular
      bacterial replication of B. abortus Strain 2308, Mycobacterium bovis Bacillus
      Calmette-Guerin (BCG) Montreal Strain 9003, Salmonella dublin Strain 5631, and
      Salmonella typhimurium Strain 14028 was evaluated in a bactericidal assay. The
      macrophages from resistant cattle were significantly superior (P < 0.05) in
      controlling intracellular growth of B. abortus, M. bovis BCG, S. dublin but not
      of S, typhimurium than macrophages from susceptible animals. Controls of all four
      pathogens correlated strongly with each other in resistant or susceptible
      macrophages. Data from resistant cattle had a tighter grouping than that of
      susceptible cattle, while data from susceptible cattle overlapped considerably
      with data from resistant animals. Therefore, this assay was considered a
      phenotypic marker of the resistant trait. For each bacterial species a percent
      bacterial survival value was used as a cut-off point to designate animals as
      resistant or susceptible. These data were compared with the in vivo challenged
      resistant or susceptible classification by using the Chi-square analyses. A cut
      off point of 70 percent bacterial survival for B. abortus designated 14 cattle as
      susceptible and seven as resistant and this correlated 100 percent with the
      number of animals designated as to the relevant category by in vivo challenge. A
      value of 65 percent bacterial survival for M. bovis BCG, and 100 percent
      bacterial survival for S. dublin correlated highly with actual numbers of animals
      designated as susceptible or resistant.

PMID- 9157687
TI  - Preparturient vaccination to enhance passive immunity to the capsular
      polysaccharide of Pasteurella haemolytica A1.
AB  - The potential to increase passive serum antibody titres to a polysaccharide
      antigen in neonates, by preparturient vaccination of the dams was investigated.
      Dairy cows in five private herds were vaccinated with a commercial Pasteurella
      haemolytica culture supernatant vaccine (Presponse, Langford Inc.), at 6 and 3
      weeks before their calculated due dates. Dams' sera, colostral whey, and post
      colostral calf sera were assayed for antibodies of the IgG1 isotype binding
      purified capsular polysaccharide of P. haemolytica A1, using an enzyme
      immunoassay. Antibody titres were analyzed using the General Linear Model
      procedure (Statistical Analysis Systems Institute Inc.). Vaccinated dams had a
      significant increase in serum antibody titre after vaccination compared with non
      vaccinates (P <0.01), and their antibody titres in colostral whey were
      significantly higher (P <0.05). Calves of vaccinated dams had significantly
      higher passive antibody titres than those of non-vaccinates (P <0.01) in all
      herds.

PMID- 9157688
TI  - Cell-mediated immune responses of lambs to experimental infection with bovine
      respiratory syncytial virus.
AB  - Primary infection of lambs with bovine respiratory syncytial virus (RSV) was
      characterised by the presence of virus-specific cytotoxic cells in the peripheral
      blood as early as 5 days post-infection. These effector cells lysed virus
      infected autologous targets in a self-restricted manner. Depletion techniques
      revealed that cytotoxic activity was largely due to OvCD8+ cells. Neutrophils
      obtained from experimentally infected lambs 5 to 10 days post-inoculation
      exhibited significant cytotoxic activity in the presence of bovine RSV-specific
      antiserum. During the same period there was a significant lymphoproliferative
      response to live or inactivated bovine RSV. Lymphoproliferative and cytotoxic
      activity coincided with the clearance of the virus from nasal secretions.

PMID- 9157689
TI  - Antigens of bovine respiratory syncytial virus in peripheral blood lymphocytes of
      experimentally infected lambs.
AB  - Eight lambs were experimentally infected with bovine respiratory syncytial virus
      (RSV) and the distribution of viral antigen in lymphocyte subpopulations studied
      by flow cytometry. Experimental infection with bovine RSV was characterised by
      significant changes in lymphocyte subpopulations. Infection was followed by a
      significant (P <0.001) reduction in the number of cells expressing the OvCD5
      epitope (T cells), due to a fall in the number of cells expressing the OvCD4
      epitope (helper) and those expressing the OvWC1 epitope (gamma/delta) 3-7 days
      post-inoculation. There was a significant increase in the number of OvCD5+ cells
      expressing the OvCD8 epitope (cytotoxic/suppressor) later. Flow cytometric
      analysis with bovine RSV-specific monoclonal antibodies revealed that viral
      antigens were present in all lymphocyte subpopulations but the main targets were
      T cells in general and OvCD4+ cells in particular. Challenge of primed lambs with
      bovine RSV had similar effects over a shorter period, followed by significant
      rises in the number of OvCD45+ (B) cells and OvCD5+ (T cells). Viral antigens
      were also present in lymphocytes subsets following challenge.

PMID- 9157690
TI  - [Ways to improve outpatient polyclinic care for servicemen].

PMID- 9157691
TI  - [The clinical diagnosis of pseudotuberculosis].

PMID- 9157692
TI  - [The multimodal therapy of surgical sepsis].
AB  - The data of clinical current of sepsis in 239 wounded with syndrome of system
      inflammatory reaction (SIR) are investigated. Frequency of sepsis in
      complications of gun-shot wounds has made 5.4%. At the same time syndrome SIR is
      diagnosed in 23.4% of cases, that was the indication to realization of the whole
      complex of antiseptic treatment. Therapy of sepsis included some components:
      drainage and removal of the septic center; the system antibacterial therapy; the
      controlled hypocoagulation; immunotherapy; active detoxication; power and trophic
      support on the basis of balanced feed. The used principles of early diagnostics
      and multicomponent therapy of surgery of sepsis have allowed to lower lethality
      up to 29.3% and in sepsis of wound--up to 9.1%.

PMID- 9157693
TI  - [Epidural anesthesia in cardiac anesthesiology (a review of the literature)].

PMID- 9157694
TI  - [The principles of guaranteeing the quality of medical care for the wounded and
      ill].
AB  - The author states four main principles of maintenance of quality of the medical
      care to wounded and patients: a principle of conformity of preparation of the
      staff to soluble problems is provided by observance of the State educational
      standards of vocational training--carrying out the professiographic analysis of
      activity of the surgeons for creation of the models of the experts, perfection of
      the educational plans and programs; a principle of development of material base
      with sharp definition of priority spheres of its development for forthcoming year
      and use of material means for development of economic base of military-medical
      institutions; a principle of strict observance of modern medical technologies,
      based on the standards of equipment, outcomes (results of work of the medical
      institutions), medico-technological and medico-pharmaceutical; a principle of
      scientific quality management on the basis of estimation of staff-organizational
      structure of medical units and institutions, treatment-diagnostic technologies
      (processes) and the results of rendering of the medical care.

PMID- 9157695
TI  - [The use of the Litoklast apparatus for the pneumatic contact destruction of
      stones in the ureter and bladder].

PMID- 9157696
TI  - [The prospects for the development of extracorporeal shockwave lithotripsy].

PMID- 9157697
TI  - [Needle-fee injections and "syringe"-related infections].

PMID- 9157698
TI  - [The psychophysiological validation of the corrective and rehabilitative problem
      with servicemen who participated in combat operations].
AB  - The necessity of psychophysiological correction and rehabilitation in the units
      is caused by peculiarities of called in Armed Forces contingent, the decrease of
      opportunities of adaptation in the part of the servicemen by virtue of individual
      peculiarities, after diseases and traumas, and also in result of adverse
      influence on the organism of the factors of military labour--extreme physical and
      mental loads, inhabitation of the objects of military engineering and arms,
      climatogeographic zones and others. In result of researches is established, that
      almost in 90% of servicemen, working at the extreme conditions and with which
      psychophysiological correction was carried out, were improved subjective state of
      health, interpersonal relations in collective, sleep was normalized.

PMID- 9157699
TI  - [Transconjunctival electro-ophthalmic stimulation in the medical and occupational
      rehabilitation of flight personnel with refractive anomalies].

PMID- 9157700
TI  - [A bibliography of the main publications in Voenno-meditsinskii zhurnal in 1985
      1996 on the problem of the healthy life style].

PMID- 9157701
TI  - [A method for the diagnosis and treatment of diseases using high-temperature
      short-term heat impulses].

PMID- 9157702
TI  - [The role of the Department of Forensic Medicine of the Military Medical Academy
      in the study of gunshot and blast trauma].

PMID- 9157704
TI  - [Allowable fluctuations in the data on the content of lipid-complex components in
      food products in chemical composition tables].
AB  - The extension of the experimental and literature data about total lipids, fat
      acids, sterins used for edition chemical Tables. In results has calculated mean
      and coefficient of variation. For the most food, exception egg, liver and so on,
      content of sterins has 85 divided by 50 mg/100g of foods.

PMID- 9157703
TI  - [The effect of vitamin- and beta-carotene-enriched products on the vitamin A
      allowance and the concentration of different carotenoids of the blood serum in
      victims of the accident at the Chernobyl Atomic Electric Power Station].
AB  - The results of clinical trials of efficiency of foods enriched by vitamins and
      beta-carotene in people suffered from Chernobyl's accident are presented. The
      level of beta-carotene in clinical diets was the same during trial. Daily
      consumption of enriched food supplying ingestion of 4-5 mg of beta-carotene
      increased the level of beta-carotene in serum by 2-4 times. The concentration of
      total carotenoides in serum was increased by 1.6 times practically at the expense
      of beta-carotene.

PMID- 9157705
TI  - [The hygienic validation of the recommended values for fluoride consumption for
      the adult population].
AB  - In trial with 21 health volunteers aged 40 +/- 1.8 years during 21 days was shown
      that the level of fluoride intake meeting the requirement all participants taking
      into account the interindividual variations in requirement must be 1.8 mg per
      day. The range of variation of homeostatic dose for fluoride make up 1.5-1.8 mg.
      The higher level (up to 4 mg/day) of fluoride intake has no medical or biological
      advisabilities.

PMID- 9157706
TI  - [The heavy metal problem in food products and the approaches to using raw
      foodstuffs with a high content of heavy metals (a review)].

PMID- 9157707
TI  - [The iodine content in the the drinking water and food products and its urinary
      excretion in Novosibirsk schoolchildren].

PMID- 9157708
TI  - [The effect of a protein concentrate from milk whey and its fractions on the
      macromolecular permeability of the intestinal barrier in rats with experimental
      food anaphylaxis].
AB  - Rats received dietary supplement of milk whey concentrate (KSP) being
      manufactured from skimmed milk by addition of apple pectin (Pec), KSP
      ultrafiltrated fractions and pure Pec during 21 day. A part of animals were
      sensitized i/p with chicken ovalbumin and finally subjected to systemic
      anaphylaxis (SA) by i/v antigen challenge. Gastrointestinal barrier
      macromolecular permeability (MP) for polyethylene glycol 4000 (PEG-4000) was
      measured by its urinary excretion after an intragastric load. MP increased
      significantly in nonsensitized rats after feeding with KSP and its high molecular
      (HM) fraction but not after feeding with low molecular (LM) KSP fraction compared
      to NaCl fed group. Feeding with Pec dramatically (5-fold) increased permeability.
      On the contrary the permeability decreased in sensitized rats subjected to SA
      when fed with KSP, its LM and particularly HM fraction the later group
      permeability being normalized down to normal value found in nonsensitized
      animals. It's concluded that KSP whey protein may be recommended for
      incorporation into specialized foods for patients with impaired gastrointestinal
      function.

PMID- 9157709
TI  - [Cholic acid sorption by food fibers].
AB  - The ability of five kinds of dietary fibers isolated from different plants for
      binding of bilious acids (BA) in vitro was estimated. The bile was derived from
      patients with obstructive hepatitis. The examined kinds of dietary fibers have a
      capacity to absorb BA. This capacity is a little lower than a pharmaceutical
      preparation bilignin. The studied dietary fibers may be recommended for
      preventive diets.

PMID- 9157710
TI  - [Clinico-biochemical validation of the use of PUFA omega-3 in patients with
      ischemic heart disease, familial hyperlipoproteinemias and hypertension].
AB  - The effectivity of diet AI, containing 20 g of fish oil eiconol, for patients
      suffering with ischemic heart disease, family hyperlipidemia and hypertension
      were checked. It was concluded that treatment with eiconol is recommended during
      4 weeks 2-3 times per year in dose of 3-6 capsules 3 times a day depending on
      degree of lipids metabolism and hemocoagulation disturbances.

PMID- 9157711
TI  - [The protection and support of the breast feeding of infants in Russia].

PMID- 9157712
TI  - [Agribusiness and the consumer market: a continuation of crisis trends].

PMID- 9157713
TI  - [Thyrotropin and thyroid hormones in human saliva before and after the taking of
      food].
AB  - Saliva of parotid or submaxillary and sublingual glands and venous blood were
      collected using the Leshly-Krasnogorskii's capsules in young men volunteers on an
      empty stomach immediately and in 30 minutes after meal. Contents of thyrothropin
      (I), 3-iodinethyronin (II) and thyroxin (III) were analyzed In saliva and serum.
      Saliva secretion was stimulated by spilled drops of 3% citric acid solution on
      tongue. It was shown that I, II and III were habitual in saliva and their
      concentration in saliva were increased after meal. More significant postprandial
      increasing of hormones were seen in saliva of parotid gland than in mixed saliva
      of submaxillary and sublingual glands. As can be justified by quick effect of
      meal secretion of hormones in saliva has reflex nature. The mechanisms of
      secretion and resources of hormones in saliva are discussed.

PMID- 9157714
TI  - [THe characteristics of the action of Khi-Mi on gastric and hepatic secretion].
AB  - The peculiarities of action of He-Me (92% of sodium glutamate and 8% sodium
      inosinemonophosphate) on gastric and liver secretions was studied in experiments
      on dog with Pavlov's isolated ventricle and dogs with bile duct, taken out on the
      skin (operation by M. F. Nesterin). He-Me exerted promotional influence on
      gastric secretion provoked by pentagastrin increasing of secretion by 3-5 times
      with prolongation of secretion time. The gastric secretion in various stages
      (nervous, secretory, intestinal) was strengthened after adding of He-Me to
      dietary meat. In that way effect of He-Me on gastric secretion is the same as
      effect of sodium glutamate but effect He-Me more strong after oral intake. He-Me
      has also choleretic effect. The data allow to re recommend He-Me as diagnostic
      and therapeutic remedy.

PMID- 9157715
TI  - ["Fat substitutes"--can nature be fooled?].

PMID- 9157717
TI  - [Prospective study of diagnosis, therapy and follow-up of acute gastrointestinal
      hemorrhage in 397 patients].
AB  - The mortality of acute GI hemorrhage in the literature varies considerably,
      depending on the study design and quality of the data evaluated. We therefore
      conducted a prospective study over 2.5 years of 397 patients with suspected acute
      GI hemorrhage at the University hospital of Erlangen for internal quality
      control. In 99% of cases diagnostic endoscopy identified one or more bleeding
      sources. 46% of the patients bled from duodenal or gastric ulcers, 21% from
      esophageal or gastric varices and 33% from other sources. 228 of the 397 patients
      (57%) were initially treated endoscopically, 76 patients (19%) experienced a
      recurrence of bleeding. Patients older than 60 years of age with a hemoglobin
      below 8 g/dl had a significantly higher rate of recurrent bleeding. The rate of
      complications during the hospital stay was 22% (n = 87), in-hospital mortality
      17% (n = 68). The rates of recurrent bleeding (28 vs. 20%), complications (24 vs.
      18%) and mortality (20 vs. 14%) were significantly higher for bleeding varices
      than for peptic ulcers. Patients with other causes of acute GI hemorrhage
      developed a recurrence of bleeding in 13%, complications in 26% and had a
      mortality rate of 19%. Bleeding varices as well as bleeding peptic ulcers and
      other causes of acute GI hemorrhage still have a high mortality and require
      intensive medical surveillance besides diagnostic and therapeutic endoscopy.

PMID- 9157716
TI  - [Established and new therapeutic approaches in dermatomyositis, polymyositis and
      overlapping syndromes].
AB  - An overview is presented on current antiinflammatory, cytostatic/cytotoxic and
      immunomodulatory treatments for immunologically mediated inflammatory myopathies
      with skin involvement. High-dose intravenous immunoglobulin (IVIG) therapy is
      discussed in the context of recent findings regarding pathogenic mechanisms of
      autoimmune diseases.

PMID- 9157718
TI  - [Meniscus lesions after isolated anterior cruciate ligament rupture].
AB  - In this retrospective study the meniscal status of 34 patients with untreated
      complete anterior cruciate ligament (ACL) tears is reported. The anterior
      cruciate ligament injury was initially documented by examination under anesthesia
      and arthroscopy. Treatment in all cases consisted of a standard protocol of early
      rehabilitation and bracing. The mean follow-up was 7.3 years. Twenty-two (65%)
      patients showed signs of meniscal pathology at an average of 2.5 years after the
      ACL injury during the follow-up period. Rearthroscopy was performed and showed a
      higher incidence of medial meniscus tears (53%) than lesions of the lateral
      meniscus (41%). The most common tear of the medial meniscus was the bucket-handle
      type, followed by the flap tear and the single longitudinal split of the
      posterior horn. Secondary reconstruction of the ACL was necessary in 18 patients
      (82%) complaining of symptoms indicative of permanent anterior instability of the
      knee. The remaining 4 patients had rearthroscopy 3.5 years after the ACL injury
      and a partial meniscectomy and ACL reconstruction was performed. 12 patients
      (35%) had no symptoms or signs of joint instability or meniscal pathology during
      the follow-up period, but discontinued their sporting activities. This study
      indicates the increasing incidence of meniscal tears during ACL insufficiency. We
      recommend that patients with ruptures of the anterior cruciate ligament should be
      investigated for meniscal tears and that early ligament reconstruction of the
      knee and meniscal repair or partial meniscectomy should be considered
      simultaneously.

PMID- 9157719
TI  - [Driver's license, driving habits and traffic safety of patients with diabetes
      mellitus].
AB  - Motoring practices of diabetic drivers are similar to those of the average
      driving population. Due to the sudden onset of disabling hypoglycemia and the
      long-term complications of the disease, particularly retinopathy, one might
      assume that diabetic drivers are more prone to road traffic accidents than the
      average driver; however, the risk is not increased. The Council of the European
      Union recently laid down guidelines for dealing with this problem, which will
      lead to the introduction of a new law in Austria governing driving licensing.
      This legislation is currently under consideration. We recommend that
      discrimination between patients requiring therapeutic regimens with potential
      hypoglycemic side effects (insulin and/or sulphonylureas) and those who are not
      at risk of hypoglycemia (controlled by diet only or oral antidiabetic drugs other
      than sulphonylureas) should be legally defined by the licensing authorities.
      Furthermore, the legal enforcement of participation by diabetic drivers in a
      structured teaching programme, with the special aim of informing on traffic
      attitudes and avoidance of hypoglycemia while driving, might be of great
      importance for safety on the road.

PMID- 9157720
TI  - [Intensive care medicine--medicine without limits?].

PMID- 9157721
TI  - [Acute infectious endocarditis].

PMID- 9157722
TI  - [The "cold" nodule of the thyroid gland: 20 years experience with 2,071 patients
      and diagnostic limits of fine needle biopsy].
AB  - The files of 2071 patients with (Tc99m)-scintigraphically "cold" thyroid nodules
      (CTN) attending a teaching hospital were analysed retrospectively. Between 1975
      and 1995 altogether 49 endocrinologists with varying degrees of experience
      carried out the clinical evaluation as well as fine needle aspiration biopsy
      (FNAB), and 33 pathologists undertook the cytological interpretation. By clinical
      criteria the CTN of 1272 patients were deemed benign, whilst malignancy was
      suspected in 301 patients (81% and 19% of evaluable cases, respectively). A
      cytological diagnosis was made in 47.3% of all FNAB performed ("benign" in 611
      patients, "follicular neoplasia" in 86, and "malignant" in 39 patients; 39.3%,
      5.5% and 2.5%, respectively). 36.5% of the clinically suspect CTN and all nodules
      with a cytological diagnosis of either "follicular neoplasia" or "malignant" in
      patients who could be followed up after the FNAB procedure were treated
      surgically, leading to a total of 420 histological diagnoses. 76% and 35% of the
      CTN classified as being suspicious of malignancy in the preoperative clinical and
      cytological evaluation, respectively, were found to be malignant on histology. A
      clinical assessment of "no abnormality" and "normal" cytology missed a malignant
      lesion in 16.3% and 15% of cases, respectively. Thus, under routine teaching
      hospital conditions, the selection of patients with CTN for surgery cannot be
      based on cytological criteria alone. The FNAB in this setting should be employed
      exclusively to supplement the clinical and scintigraphically findings.

PMID- 9157724
TI  - Hepatectomy: the opening of the main portal and umbilical fissures.

PMID- 9157723
TI  - [Definition and evaluation of a documentation standard for intensive care
      medicine: the ASDI(Working Group for Standardization of a documentation system
      for Intensive care medicine) pilot project].
AB  - OBJECTIVES: A comparison of data from different intensive care units (ICUs) needs
      standardized documentation. In this study the ASDI documentation standard for
      intensive care was tested in clinical practice. Goal of the study was to evaluate
      parameters and functionality required for a national, interdisciplinary
      documentation system for intensive care. DESIGN: 13 ICUs participated in a 4-week
      trial using the provided program for documentation of all admitted patients
      during the observation period. In addition, a questionnaire was distributed to
      the unit coordinators. RESULTS: 376 patients were documented in 1591 patient
      days. Valid SAPS II scores were found in only 29% of the discharged patients
      (39.1 +/- 15.5 points). Time needed for data entry exceeded preset limits (ten
      minutes per patient and day) in 38% of the cases. All participants affirmed the
      necessity of a documentation standard for intensive care, giving quality control
      and cost analysis as the most important reasons. CONCLUSION: The ASDI data set
      fitted existing needs very closely. Only 7 out of 122 parameters (5.7%) were
      found to be superfluous and thus removed. Measures to reduce documentation effort
      to the default limits were a) a new, date orientated concept for manual
      recording, b) rede-sign of the user interface with new, user friendly data entry
      possibilities, and c) the integration of statistical analysis and reports in the
      documentation system. The revised data set represents a broad-based consensus,
      which seems to be well-suited as foundation for the national quality assurance
      program.

PMID- 9157725
TI  - MODS/SIRS conditions.

PMID- 9157726
TI  - [Quality and quality assurance of medical education and continuing medical
      education. Proceedings of a symposium. Wurzburg, 22-23 September 1995].

PMID- 9157727
TI  - [Initial experience with the PCDiary: software for physicians for documenting and
      evaluating individual learning].
AB  - A computer diary was developed for physicians to create a portfolio of their self
      directed learning. Each item of learning is recorded in the form of a question
      along with the stimulus, the learning resources used and the outcome planned for
      the learning. The records of 123 physicians which volunteered to use the diary
      were analyzed. Their response to the software, elicited by survey, is described.
      Items of learning were most often stimulated by scanning the literature and while
      seeking information to manage a patient. The physicians recorded their intent to
      change their practice as the outcome to learning most often when the learning was
      stimulated while managing a patient. One-half of the physicians reported that
      keeping the diary made them think about their patient care.

PMID- 9157729
TI  - [Evaluation of HIV-related continuing education programs for established
      physicians].
AB  - Neither the HIV-specialists, the cooperating specialists, nor the family
      physicians are required to have special qualifications to treat HIV-infected
      patients. CME-courses don't consider the very different fields of interest of the
      participants or that the transfer of knowledge is quite important to ensure the
      quality of medical care. Questionnaires regarding HIV related topics were
      distributed in nine HIV-CME courses (9/93-5/94) of the DAGNA (German association
      of panel physicians treating HIV-infected patients) in cooperation with the
      society of physicians of Germany and the association of public health insurances.
      The satisfaction of the participants, the topics with regard to their relevance
      for the task group, the importance for the daily routine, and didactic manners
      were investigated. Feed-back: 41%. Although the general impression of most
      participants was "quite satisfying" (87%) there was some critic regarding special
      aspects. The rating of the courses depended on the level of qualification.
      Specialists in internal medicine rated the relevance for their medical practice,
      the topics and the possibility of contribution more positive than other
      specialists or general practitioners (GP). In general, there was a great
      difference regarding the rating of the courses among the participants because of
      their individual level of qualification and knowledge. In order to take the
      different levels of qualification and demands for topics into account there must
      be graduated courses: specialists, experts, elementary and beginner courses. The
      basic courses should contain not only the lectures but also the possibility of an
      active contribution of the participants. Adequate guidelines have to be
      developed.

PMID- 9157728
TI  - [CASUS model trial. A computer-assisted author system for problem-oriented
      learning in medicine].
AB  - The CASUS-project, a three year publicly funded effort to improve the quality of
      continuing medical education in Germany, has one major goal: The development and
      evaluation of an easy-to-handle author-system for problem-oriented learning in
      medicine. On the theoretical basis of the cognitive apprenticeship-approach, the
      concept of a teaching and learning database as a hypermedia system was built. The
      student should learn to manage authentical problems in the form of authentical
      clinical cases. The step-by-step learning process is expert-guided by the
      clinical authors of each case. The creation of various differential diagnoses by
      the learner is strongly supported in the process. The structure of the program
      can also be used for case-based examinations. In parallel to the technical
      development, a case-selection process for medical students students in internal
      medicine was initiated. About 120 relevant diseases were identified to be
      represented in the CASUS-case library. Prevalence, transferability of knowledge,
      treatability, urgence of treatment and preventive aspects were used as selection
      criteria. The system will be evaluated during the implementation of test cases
      and will then be available to be used by authors and students on a routine basis
      in 1997.

PMID- 9157730
TI  - [Goals, content and evaluation of training seminars for quality circle
      moderators].
AB  - In this paper, our experience with training courses for quality circle moderators
      is reported. Basic principles of the peer review method in general and the
      specific model of the topic-oriented quality circle approach in the ambulatory
      care in Sudbaden is described. Peer review in quality circle groups demands
      specific participants' skills. Thus, training courses for quality circle leaders
      have been set up to prepare moderators for their task. Attention is given to the
      goals and contents of training courses for physicians. Key elements are the
      supervisory role of the moderator and specific tasks in handling the group
      dicussions. Evaluation questionnaires after the courses showed that the
      participants (n = 41) judged the programme very positively.

PMID- 9157731
TI  - [Conception, implementation and evaluation of the new general medicine continuing
      education curriculum in Sudbaden].
AB  - Since 1994, seminars for the new curriculum in general practice are conducted by
      the Academy of Continuing Medical Education (consists of the regional medical
      board and the association of public health insurance in Sudbaden). Specialists of
      different medical disciplines supported by general practitioners in the role of
      moderators are preparing and teaching a wide range of topics. The general
      practitioners are supervising the different courses, thus, facilitating the
      learning process of the participants. Furthermore, the facilitators have to work
      out the specific needs and requirements of general practice and family medicine.
      The topics are presented in a form of lessons and clinical cases discussed in
      small groups (problem-oriented approach). The evaluation of two seminars was
      carried out in 1994 and 1995 including two thirds of the complete curriculum in
      general practice. From the positive results of the evaluation, modification and
      improvement of the didactic concept for future seminars in 1996 are derived.

PMID- 9157732
TI  - [Windmill principle versus clockwork principle--tradition and interaction in
      academic lectures. A. N. S. A. Radiologica].
AB  - In reply to depersonalization of teaching, students hiding behind anonymity and
      their decreasing effective presence in campus life, academic teaching has to
      become practice-oriented, attractive and at least more effective. The traditional
      teacher-based lecture competes with student-centered and issue-related academic
      events like problem-based learning, thus, concerning student-teacher interaction.
      The model of a clockwork represents the components of a traditional lecture. The
      model of a windmill is suitable for explaining synergistic effects in scope and
      experience during an interaction concerned lecture. An example of student-teacher
      interaction and students' activation even in a preclinical course of lectures on
      anatomy and radiology is given. A high response and acceptance of the lecture is
      assured by structure-and process-oriented features.

PMID- 9157733
TI  - [Status of radiation protection courses for physicians--plea for a change in
      paradigm].
AB  - The purpose of this study was to evaluate the acceptance of the statutory course
      of radiation protection, which is attended by physicians. As a first step towards
      problem based quality management, an anonymous questionnaire was used to assess
      the participants' opinions. The present methods in teaching, practice-orientation
      of the educational objectives, the prize and efficiency of the course were judged
      poor. Neither valid indicators of quality nor a quality management of the course
      exists. Facing the status quo and future demands within the medical community and
      society there is a serious need for reshaping radiology. It is emphasized that
      instead of marginal corrections only a strategic and fundamental approach to a
      paradigmatic reorganization will meet success.

PMID- 9157734
TI  - [Pain therapy for patients with tumor diseases. Quality assurance].
AB  - Medical care for patients with cancer is in worldwide discussion about the
      therapeutic goals. Additionally to cancer therapy, pain therapy and symptom
      control is getting more and more attention. The definition of structural quality
      aspects, process quality and resulting quality provides a valuable tool for
      analyzing status and goals in cancer pain therapy. In this paper, we present a
      computerized documentation program which leads through pain analysis to
      initiation, evaluation and control of therapeutic results following WHO
      guidelines. Information is offered during the documentation procedure. The
      program fills therapeutical (documentation) gaps during everyday practice
      concerning pain and symptom control in cancer patients. The program presents a
      kind of "on demand" continuing education.

PMID- 9157735
TI  - [Concept and outcome of general practice quality circles on the topic of diabetes
      mellitus].
AB  - In Saxonia, an agreement of shared care was reached between health insurances and
      the society of general practitioners with the objective to have a better medical
      care for patients with diabetes mellitus. This model of shared care means
      integrated medical care for out-patient diabetics between general practitioner
      and specialists. It must be accompanied by quality assurance measures. After a
      training of moderators according to a structured programme of the Central
      Research Institute for Outpatient Health Care, quality circles started with seven
      to ten members and two moderators in five Saxonian cities in May 1994. General
      practitioners interactively improved their medical knowledge about diabetes
      mellitus during five sessions with two hours each. The regional specialist
      participated in the first and the last session. He also answered open questions
      left in a mail box. Based on patient data the following results were achieved:
      553 documentations.

PMID- 9157736
TI  - [Quality assurance in basic psychosomatic care. Report of an expert survey within
      the scope of the Federal Public Health Administration instigated pilot project].
AB  - This article outlines a nationwide quality improvement project in counselling
      funded by the German Ministry of Health. To develop the project, expert surveys
      and consensus conferences are currently organized by the coordination center. A
      questionnaire with mainly open questions was sent to 32 teachers in general
      practice. Counselling for psychiatric, psychosomatic and psychosocial problems in
      primary care was regarded as an important field for quality assurance. The
      experts believed short psychotherapy to be an integral part of family medicine as
      some 30% of our patients present with complaints caused by psychosocial or
      psychological reasons. However, only some 70% of patients receive a specific
      treatment. The experts rated better recognition of psychosomatic problems as the
      most important area for quality improvement. Suitable interventions to improve
      the physicians' ability in the area mentioned were continuing medical education,
      balint groups, quality circles and flexible guidelines. The experts made
      invaluable contributions to the development of a practice documentation for
      psychosocial problems.

PMID- 9157737
TI  - [Cost effectiveness and evaluation of a structured therapy and education program
      for insulin-treated type II diabetic patients in Bradenburg].
AB  - The aim of the study was to evaluate the practicability and efficacy of a
      structured treatment and teaching programme (STTP) for Type II diabetic
      outpatients on conventional insulin treatment after introducing a remuneration
      for physicians. Reimbursement policy was introduced in the state of Brandenburg,
      Germany, in July 1993. Between August 1993 and February 1994, 108 practices in
      Brandenburg participated in a postgraduate seminar, which is a prerequisite for
      remuneration. Within the first year 10% of the target group of physicians
      participated in the seminars. A standardised interview was performed with 103
      physicians. Twenty of the practices who had performed STTP were visited in order
      to collect data on all the patients who had participated in the programme. The
      seminar and the programme were well accepted. An improvement of HbA1c levels was
      observed in patients (n = 54) who had started insulin treatment (9.7 +/- 1.6% of
      total Hb before, 8.2 +/- 1.3% of total Hb after the programme) and in those (n =
      189) who were already being treated with insulin before the STTP (9.6 +/- 2.5% of
      total Hb before, 8.1 +/- 1.4% of total Hb after the programme). The results of
      the study demonstrate the efficacy and practicability of an STTP for Type II
      diabetic patients on conventional insulin therapy in ambulatory health care.

PMID- 9157738
TI  - [Continuing education seminar for general practice in the North Rhine District
      Medical Group. Results of of survey of participants during March to June 1995].
AB  - Since 1994, new rules for continuing medical education (CME) for general
      practitioners have been implement in Germany. It is currently necessary to
      participate in internal medicine, surgery and general medicine for three years.
      For the first time, CME seminars have been implemented. Postgraduates have to
      absolve 240 hours for becoming general practitioner. A first evaluation from the
      area of the "Nordrheinische Akademie fur arztliche Fort- und Weiterbildung"
      (Academy of continuing medical education) is presented. The results are discussed
      in the context of further questions looking into the future of CME training of
      general practitioners.

PMID- 9157739
TI  - [Cerebral cognitive deficits in the aged. Diagnostic and therapeutic standards:
      organization of strategies for problem detection and solution].
AB  - This paper reports the results of a representative survey which was performed in
      cooperation with 145 family physicians and 14 primary care neuropsychiatrists
      (response rate 83.2%) in the area of Gottingen, Germany. With the use of a
      standardised interview referring to written sample case histories, we
      investigated the diagnostic and therapeutic management of memory disturbances in
      old age. The results showed, that dementia and depression are underdiagnosed in
      primary care, and that memory disturbances are mainly regarded as consequences of
      disturbed cerebrovascular perfusion. About 70% of all physicians would prescribe
      a cognition enhancer, however about a third of them would do it in spite of major
      doubts about their efficacy. The results underline the necessity of continuing
      education especially with regard to early diagnosis of dementive and affective
      disorders in later life. The development of therapeutic standards in this area
      should take "irrational" motives into account. Appropriate exemplary case
      histories seem to be a potentially useful tool for the measurement of physicians'
      competence and its changes.

PMID- 9157740
TI  - [Goal analysis of participants and moderators of general practice quality
      circles].
AB  - Quality circles (peer review) are a process of a continuous, systematic and
      critical reflection of care providers on their own and colleagues' performance by
      using structured procedures with the aim of achieving a continuous improvement.
      Main goal of the topic-oriented quality circle model in Sudbaden (Germany) is the
      development of guidelines for primary health care. The quality circle programme
      of the society of health insurances of Sudbaden is currently given a systematic
      evaluation. The results presented refer to 246 participants and moderators of 25
      groups who have completed questionnaires. Attention is given to the general goals
      of the doctors participating in quality circle groups. When asked about the most
      important goals of peer review the participants scored the highest ranking on (1)
      exchanging practice experiences with colleagues (2) the personal reflection of
      one's way of working (3) agreeing on guidelines and targets for desirable
      performance and (4) developing guidelines for general practice. From the results,
      conclusions regarding the concept of quality circles and the methods for
      developing practice guidelines are drawn.

PMID- 9157741
TI  - [Organization of practice oriented knowledge structures by the "cognitive
      apprenticeship" method].
AB  - The introduction of the new German specialist for psychiatry and psychotherapy
      increased the requirement for more integrated and flexible clinical training
      programs for residents. The integration of this multitude of more sophisticated
      diagnostic and therapeutic strategies in an individualized treatment plan for
      each patient requires new teaching strategies. The instructional method
      "Cognitive Apprenticeship" in acquisition of treatment planning-competence is
      discussed within a curriculum framework.

PMID- 9157742
TI  - [The army medical service: past, present, and future].
AB  - The changes in the geopolitical situation after the dissolution of the Warsaw
      pact forced many western governments to reform drastically their armed forces.
      Moreover, the postponing of the conscription gave this restructuring a very
      particular dimension. Despite all this alterations the fundamental missions of
      the Medical Service of the Armed Forces have not changed. They still consist of
      maintaining the operational readiness of the troops, taking care of the wounded
      and reducing physical and mental handicaps. Therefore an entity of levels of
      consistent and capable medical care is needed. The rational construction of this
      complete and fulfilling chain of help, from point of wounding to the discharge
      from the hospital on national territory is the right to exist for an autonomous
      Medical Service. It goes without saying that this treatment must have the same
      quality standards as those used in the civilian health care system. Taking this
      into account the Medical Service of the Armed Forces integrated its means into
      civilian services for urgency and disaster medicine. In the scientific field
      there are a lot of close contacts and agreements with several universities in
      order to deal with the military aspects of the medical research. It is in fact
      the ethical duty of the Medical Service to provide for optimal care to the Armed
      Forces. Can a nation omit this? Will arguments of budgetary kind and the relative
      international "detente" again do forget us the lessons learned from the past? Is
      an autonomous Medical Service a superfluous luxury?

PMID- 9157743
TI  - [Avian Chlamydia psittaci phyla and their pathogenic significance for turkeys].
AB  - The present study demonstrates that Chlamydia psittaci is an important cause of
      respiratory disease in turkeys in Europe. The serotyping of isolates revealed
      that European turkeys frequently become infected with Chlamydia psittaci serovar
      D strains, but also can become infected with serovar A and B strains. In turkeys,
      differences in pathogenicity were observed not only between strains belonging to
      the serovars A (strain 84/55), serovar B (strain 89/1326) and serovar D (Texas
      Turkey strain and strain 92/1293), but also between two strains belonging to the
      same serovar D (Texas Turkey strain and strain 92/1293). In order to find an
      explanation for these differences in pathogenicity, the pathogenesis of the
      infection was studied in specific pathogen free turkeys. However, for all three
      serovars examined a similar pathogenetic sequence of events was deduced. In order
      to try and elucidate the observed differences in pathogenicity between different
      Chlamydia psittaci strains, the bacterium-host cell interaction was studied in
      BGM cell culture using transmission electron microscopy and immuno electron
      microscopy. Strains most pathogenic for turkeys, namely the serovar A strain and
      strain 92/1293 (serovar D) produced significantly larger inclusions with more
      numerous infectious organisms, produced the most severe degenerative changes in
      the host cell an also replicated freely in the cytoplasm of the host cell.

PMID- 9157744
TI  - [The involvement of prostaglandins in the inhibiting effect of endotoxin on the
      myoelectric activity of the gastrointestinal system in pigs].
AB  - The probable involvement of prostaglandins in the myoelectrical response of the
      antrum pylori and small intestine to endotoxin (LPS) was studied in the piglet.
      In these experiments the influence of I.V. infusion of PGF2 alpha and PGE2 and of
      I.V. injection of LPS, without and with indomethacin (INDO) pretreatment, on
      myoelectrical activity of the antrum pylori, duodenum, jejunum and ileum as well
      as on some clinical and haematological parameters was studied. Infusion of the 2
      PG's, especially PGE2, inhibited myoelectrical activity of the antrum pylori.
      PGE2 also reduced duodenal activity. PGF2 alpha was without effect on duodenal
      and jejunal activity, but stimulated ileal activity. Both PG's induced fever,
      nausea, vomiting and sedation or excitation. With the higher dose of PGE2
      diarrhoea was also observed. Injection of LPS induced identical myoelectrical and
      clinical changes, as described for PGE2. However, endotoxin did not induce
      diarrhoea. Depending on the dose, administration of LPS resulted in a
      leukocytosis or a leukopenia together with an increase in band neutrophils.
      Following pretreatment with INDO the effects of LPS on gastrointestinal
      electrical activity were reduced and its clinical symptoms were nearly completely
      inhibited. The haematological changes induced by LPS, however, were not
      influenced by INDO. These experiments suggest a possible involvement of the PG's
      in the clinical symptoms and in the initial inhibitory effect of LPS on
      myoelectrical activity especially of the antrum. However, the induced
      haematological changes are probably not mediated by the arachidonic acid pathway.

PMID- 9157751
TI  - [The psychological characteristics of patients with neurological manifestations
      of lumbar osteochondrosis].
AB  - Both clinical-neurological and psychological examinations of 42 patients with
      neurological manifestations of lumbar osteochondrosis with chronic or chronic
      recurring course were carried out. The main features of personality in most cases
      were anxiety, hypochondria, passivity and demonstrativity. The clinical signs of
      nonspecific psycho-emotional tension was found in 70% of cases. Its level
      correlated negatively with the effectiveness of the treatment. It was established
      that the negative influence of personality on the course of disease and on the
      effectiveness of its therapy was connected with the predisposition of such
      individuals to unfavourable type of reaction toward disease and to development of
      psychic adaptation disorders.

PMID- 9157752
TI  - [Obsessive-phobic disorders in anorexia and bulimia nervosa].
AB  - The data on 1500 patients with syndrome of anorexia and bulimia nervosa were
      summarised in terms of clinical-psychopathological, catamnestic and experimental
      psychological investigation. This syndrome was considered as one disease which
      presented the variation of borderline mental pathology or the manifestation of
      schizophrenic process. Obsessive-phobic disorders were observed in majority of
      patients (95%). Such disorders were characterized by prevalence of obsessive
      phenomena with food content. It was noted that diagnosis and prognostic
      significance had either obsessive-phobic disturbances or obsessions with other
      content which occurred on the initial stage of disease, before development of
      syndrome of anorexia and bulimia and in period of pronounced cachexia. The
      therapeutic resistance of obsessive disturbances in patients with anorexia and
      bulimia were emphasized as well as the necessity of prolonged ambulatory
      treatment of such patients.

PMID- 9157753
TI  - [The characteristics of borderline mental disorders in veterans of the war in
      Afghanistan].
AB  - 243 veterans of war in Afghanistan (1979-1989) were observed during 1990-1993.
      Mean age was 28 +/- 4.9 years (21-48 years). Period of return to conditions of
      peaceful existence was 2-11 years (mean value-6.3 +/- 2.5 years). The borderline
      mental disorders were found in 29.6% of cases where neuroses dominated (47.2%).
      The affective pathological manifestations prevailed on syndromological level
      (53.8%). Deformations in personality features termed as "combatant accentuation"
      and "combatant psychopathization" preceded above-mentioned alterations. The
      former disorder was revealed during the war and had common features in all the
      soldiers. Alcoholic abuse was observed in half of the veterans (125 individuals 
      51.5%). Somatic pathology was found in 60.5% (diseases of digestive and
      cardiovascular systems prevailed).

PMID- 9157754
TI  - [A pain syndrome of compression-reflex origin: the mechanisms of its development
      and the means for its therapeutic management].
AB  - Complex observation and treatment of 112 patients with compressive-reflex
      syndromes of cervical osteochondrosis with pain as the leading clinical
      manifestation resulted in elaboration of the scheme of its pathogenesis. The main
      links of pathological process development as well as their relationships were
      described. The main means and methods of the correction of algesic syndrome
      development were determined on the basis of both own investigations and literary
      data. The peculiarity of this study was the inclusion of Xydiphone (the Russian
      made drug from complexons group) in pathogenetic therapy. Its positive medical
      effect in treatment of the disease described was established.

PMID- 9157755
TI  - [Magnetic and electromagnetic stimulation in the combined treatment of patients
      with paralysis of the mimetic musculature].
AB  - The original method of treatment of patients with postoperative paresis of mimic
      muscles wis offered. The method included the use of two therapeutic factors:
      magnetotherapy and electromagnetostimulation of peripheral branches of facial
      nerve. The principles of combined influence of both components were described in
      detail. Data on functional control of treatment results confirm the reparation of
      peripheral branches of facial nerve.

PMID- 9157757
TI  - [The mechanisms of pain in root compression].
AB  - It is shown that antidromic stimulation of peripheral nociceptors induced by
      radicular compression is the initial pathogenetic factor of pain in patients with
      so-called paralytic sciatica and trigeminal neuralgia. Subsequently, segmental
      and suprasegmental mechanisms of pain retention are involved. The prevalence of
      one or another pain mechanisms at different stages of trigeminal neuralgia may
      determine the choice of adequate therapy.

PMID- 9157756
TI  - [The treatment of the phantom pain syndrome with tizanidine].
AB  - The authors carried out estimation of analgetic effect of tisanidin by double
      blind test in patients with phantom limb pain syndrome. 14 patients took the
      medicine in a dose of 12 mg/day and 5 patients took placebo at the same dose.
      Characteristics and intensity of pain were estimated in accordance with McGill
      pain questionnaire and visual analogue scale. Pain possessed more than one
      sensory characteristics in the majority of patients. Tisanidin had a significant
      analgetic influence on all type of phantom limb pain: "neuralgic"--acute,
      shooting, transitory, "causalgic"--hot, burning, searing, "cramping" pain. Pain
      sensation did not decrease only in one of 14 patients treated with tisanidin. The
      authors explain the effectivity of the drug for treatment of phantom limb pain of
      different sensory modality by variety of the mechanisms of its therapeutic
      action, the capacity to decrease the releasing of excitatory neurotransmitter
      amino acids and the influence on alpha 2-adrenoceptors.

PMID- 9157758
TI  - [Intersensory correlations in diabetic neuropathy during adaptation to intervalic
      normobaric hypoxia].
AB  - The state of vibration sensitivity and of gustatory perception as well as the
      influence of interval hypoxic training on these indices were estimated in 21
      patients with insulin-independent diabetes mellitus (IIDM) without neuropathic
      manifestations, in 21 analogous patients with neuropathic manifestations and in
      16 individuals with neuropathies of nondiabetic genesis. The improvement of
      indices studied was observed in patients with neuropathies. Interval hypoxic
      training may be recommended for the treatment of distal neuropathies including
      the patients with IIDM in the state of compensation.

PMID- 9157759
TI  - [The DNA diagnosis of a familial case of Kennedy's spinal and bulbar amyotrophy].
AB  - Seven relatives of previously described proband with X-linked Kennedy's spinal
      and bulbar muscular atrophy (SBMA) were investigated by means of clinical,
      biochemical and molecular genetic methods. The patients' age was 13-70 years.
      Clinical and biochemical investigations revealed SBMA in two males. Molecular
      genetic analysis by means of polymerase chain reaction (PCR) revealed
      pathological expansion of trinucleotide CAG repetitions in 5'-region of androgene
      receptor gene in both patients. Five heterozygous female carriers were discovered
      meanwhile. PCR-method permitted to diagnose the disease exactly, to reveal
      heterozygous carrier of pathological gene and to perform potential prenatal
      diagnosis.

PMID- 9157760
TI  - [The individual characteristics of the cytoarchitectonics of subcortical-stem
      formations in the human brain].
AB  - Both quantitative and qualitative analysis of individual cytoarchitectonic
      peculiarities of Meynart's nucleus as well as of external part of dorsomedial
      nucleus of thalamus was performed in mentally normal individuals. The series of
      brain's 20-microns sections stained with cresyl violet were studied. Some
      individual morphological qualitative and quantitative peculiarities were
      evaluated in Meynart's nucleus and in dorsomedial nucleus of thalamus. A number
      of pronounced cytoarchitectonic peculiarities were revealed in above-mentioned
      cerebral structures of the persons with outstanding abilities (the cases were
      taken from the special collection of Moscow Institute of Brain of Russian Academy
      of Medical Sciences).

PMID- 9157761
TI  - [The patients of the psychiatric office of a polyclinic: patients undetected by
      the clinic or a new contingent?].
AB  - Epidemiology study of patients in primary care settings has shown prevalence of
      borderline mental disorders (41.58 per 1000 population) in comparison with
      patients of psychiatric outpatient clinic (11.4 per 1000). The question arises
      were those undetected by psychiatric out-patient clinics (those who didn't visit
      psychiatrist for individual reasons) or they represented another contingent.
      Comparative analysis of groups standardized on nosological, syndromal and
      educational levels revealed that there were various contingents of patients. The
      main difference was determined by different duration of disease before the first
      visit to psychiatrist, that reflected various severity of the disease (less
      severity of the disease was observed in patients of primary care institutions).

PMID- 9157762
TI  - [The geriatric psychiatric day hospital: an analysis of 5 years of activities].
AB  - 233 patients (53 men and 180 women) at the age of 60 years and older were treated
      in day gerontopsychiatric out-patient clinic for 5 years. 60-69 year old patients
      prevailed (146 individuals). Nearly all mental diseases characteristic for the
      old age were found in such patients; majority of patients suffered from
      schizophrenia (31.3%) and affective pathology (25.8%). Vascular form of dementia
      prevailed among the patients with dementia while atrophic degenerative dementia
      was rarely observed (2 patients). Syndromological distribution revealed that the
      main groups were formed by patients with depressions (41.6%) as well as
      individuals with neurosis- and psychopathic-like conditions (37.3%). Mental
      disorders with paranoid syndromes were observed in 8.6% of the patients. It is
      shown that day gerontopsychiatric out-patient clinic had some preferences in
      comparison with usual mental hospitals and psychoneurological out-patient clinic.

PMID- 9157763
TI  - [Muscle spasms].

PMID- 9157764
TI  - [Painful muscle spasms].

PMID- 9157765
TI  - [Spasticity].

PMID- 9157766
TI  - [The functional heterogeneity of the human caudate nucleus].
AB  - Combined clinical-neuropsychological investigation of 26 patients with vascular
      malformations of caudate nucleus (CN) was performed both before and after
      surgical removal of the malformation. Arterial-venous malformations were located
      in the head (12 cases) of CN, in its corpus (9 patients), in both head and corpus
      (5 individuals). Verification of the malformation's location was carried out
      according to data of computer tomography, angiography, as well as during the
      operation. It was revealed that postoperative syndromes were closely related in
      patients with both the side of CN's alteration and with the region of the damage.
      The clear perseverative syndrome was observed when left CN, and especially its
      head was damaged. When the corpus of the left CN was damaged perseverations were
      slighter. Meanwhile faint alienation of the word's meaning as well as the slight
      alterations of evaluation of rhythm's estimation were observed in such cases.
      Disorders of the perception were observed mainly when the right CN and especially
      its corpus was damaged.

PMID- 9157768
TI  - [Apropos the content and format of this journal].

PMID- 9157767
TI  - [Cardiovascular diseases and depressions].

PMID- 9157769
TI  - Slow-release sodium fluoride in osteoporosis.

PMID- 9157770
TI  - Fluoride: the verdict is in, but the controversy lingers.

PMID- 9157771
TI  - Age-related changes in osteogenic stem cells in mice.
AB  - Osteoblasts arise from partially differentiated osteogenic progenitor cells
      (OPCs) which in turn arise from undifferentiated marrow stromal mesenchymal stem
      cells (MSCs). It has been postulated that age-related defects in osteoblast
      number and function may be due to quantitative and qualitative stem cell defects.
      To examine this possibility, we compared osteogenic stem cell number and in vitro
      function in marrow cells from 4-month-old and 24-month-old male BALB/c mice.
      Histologic studies demonstrated that these mice undergo age-related bone loss
      resembling that seen in humans. In primary MSC cultures grown in media
      supplemented with 10 nM dexamethasone, cultures from older animals yielded an
      average of 41% fewer OPC colonies per given number of marrow cells plated (p <
      0.001). This implies that for a given number of marrow cells there are fewer stem
      cells with osteogenic potential in older animals than there are in younger
      animals. The basal proliferative rate in cultures from older animals, as measured
      by 3H-thymidine uptake, was more than three times that observed in cultures from
      young animals (p < 0.005). However, the increase in proliferative response to
      serum stimulation was 10-fold in the younger cultures (p <0.001) and
      insignificant (p <0.4) in the older cultures. Colonies in both age groups became
      alkaline phosphatase positive at the same rate, and virtually all colonies were
      positive after 12 days of culture. Cultures from both age groups produced
      abundant type I collagen. These studies suggest that defects in the number and
      proliferative potential of MSCs may underlie age-related defects in osteoblast
      number and function.

PMID- 9157772
TI  - Phosphorylation of the cytoplasmic tail of the PTH/PTHrP receptor.
AB  - Activation of the G protein-coupled receptor for parathyroid hormone (PTH)/PTH
      related protein (PTHrP) produces homologous desensitization of receptor
      signaling. We have shown recently that the opossum PTH/PTHrP receptor stably
      expressed in human embryonic kidney (HEK) 293 cells is phosphorylated upon
      agonist binding and upon activation of serine/threonine protein kinases (PKA and
      PKC), an event which for some G protein-coupled receptors has been linked to
      desensitization. To locate the sites of phosphorylation, mutated forms of the
      opossum PTH/PTHrP receptor were stably expressed in HEK 293 cells, and ligand
      stimulated receptor phosphorylation was evaluated. The five serine and threonine
      residues of the third cytoplasmic loop of the receptor were not required for
      receptor phosphorylation. Basal and ligand-induced phosphorylation were, however,
      completely abolished upon deletion of all but the 16 juxtamembrane residues of
      the cytoplasmic C-terminal tail of the receptor, even though this truncated
      receptor resembled the wild-type receptor in its level of expression based on
      Western blotting and radioligand binding. To identify further the phosphorylation
      sites, the 129 amino acid C-terminal tail of the rat PTH/PTHrP receptor was
      expressed in E. coli as a recombinant glutathione S-transferase fusion protein.
      Elimination of a single PKA consensus site in the tail (serine 491) resulted in >
      or = 90% loss of PKA-mediated phosphorylation, identifying this as the
      preferential site for PKA, with two other sites (serine 473 and/or 475) being
      minor sites. Phosphorylation by PKC occurred largely in the proximal portion of
      the tail, whereas beta-adrenergic receptor kinase 1 (beta ARK1) phosphorylated
      more distally in the tail. The ability of these kinases to phosphorylate the
      PTH/PTHrP receptor at distinct sites on the cytoplasmic tail may allow
      differential regulation of receptor signaling and trafficking.

PMID- 9157773
TI  - Administration of the bisphosphonate ibandronate (BM 21.0955) by intravenous
      bolus injection.
AB  - Bisphosphonates (BPs) are used for the treatment of both benign and malignant
      diseases characterized by increased bone resorption. Because of their potential
      nephrotoxicity, currently available BPs have to be administered by slow
      intravenous infusion, with conventional doses requiring an infusion time of at
      least 2 h. In the present investigation, we evaluated the safety and efficacy of
      the new BP ibandronate as administered by intravenous bolus injection. On day 0,
      15 normocalcemic breast cancer patients with bone metastases were treated with 3
      mg of ibandronate injected intravenously over 60-120 s. Ibandronate treatment led
      to significant decreases in serum levels of calcium (p < 0.0001) and phosphate (p
      < 0.0001) and to subsequent increases in serum concentrations of parathyroid
      hormone (p <0.0001) and calcitriol (p <0.0001). Moreover, there was a significant
      reduction in the urinary excretion of calcium (p <0.0001), pyridinoline (p
      <0.001), and deoxypyridinoline (p < 0.0001). Three serious adverse events were
      observed: vomiting (WHO grade 3), pulmonary infection (WHO grade 2), and
      deterioration of a pre-existing impaired glucose tolerance (WHO grade 3). Only
      vomiting appeared to be related to administration of the drug. The most frequent
      nonserious adverse events were 10 cases of transient clinically asymptomatic
      hypocalcemia and 8 cases of asymptomatic hypophosphatemia. Serum levels of
      creatinine and urea nitrogen did not increase, nor did creatinine clearance
      deteriorate. When tested with the dipstick method, proteinuria was present in
      five (33%) patients prior to ibandronate treatment (median protein concentration,
      30 mg/dl). Following the BP injection, seven (47%) patients showed slight
      (highest protein concentration, 30 mg/dl) transient proteinuria at at least one
      time point, of which six cases appeared in conjunction with leucocyturia and
      three with microhematuria. Side effects specific to aminosubstituted BPs (fever,
      reduction in white blood cell counts, and lymphocyte counts) were not seen in
      these 15 patients. In conclusion, a single intravenous injection of 3 mg of
      ibandronate significantly inhibited osteoclast activity as reflected by the
      decrease in serum calcium and in urinary parameters of bone resorption. Serum
      creatinine levels and estimates of creatinine clearance were not affected by
      therapy. However, before repeated bolus injections of ibandronate at this dosage
      can be recommended for further clinical trials, whether a relationship exists
      between the transient pathological urinary findings and injected ibandronate
      needs to be determined.

PMID- 9157774
TI  - Bone quality factor analysis: a new noninvasive technique for the measurement of
      bone density and bone strength.
AB  - The sensitivity of bone mineral density (BMD) as a predictor of fracture risk is
      limited by the fact that this index does not take into account the geometrical
      and material characteristics of bone. In contrast, both BMD and bone architecture
      influence the quality factor (QF), the fraction of the inverse of the energy lost
      in one cycle of deformation. In this study we have compared the sensitivity of a
      QF analyzer and dual-energy X-ray absorptiometry (DXA) in detecting the changes
      induced by ovariectomy (OVX) on the QF, impact strength, and BMD of the femur of
      mature rats. QF and BMD were measured noninvasively before and 4 weeks after OVX
      or sham operation using a QF analyzer developed in our laboratory and a Hologic
      QDR 2000 bone densitometry, respectively. Impact strength was measured in excised
      femurs at the end of the study. The in vivo short-term precision (coefficient of
      variation) of the QF analyzer was 1.9%. BMD and QF measurements were highly
      correlated (r = 0.80,p <0.0001). At baseline, QF and BMD were similar in OVX and
      sham-operated rats. At 4 weeks, BMD was 14.7 + or - 0.9% lower than at baseline
      (p < 0.001) in OVX rats and 5.3 + or - 1.3% lower in sham-operated rats (p
      <0.05). QF decreased 36.0 + or - 2.8% (p <0.0001) in OVX and 10.6 + or - 3.6% in
      sham rats (p <0.01). As a result, at 4 weeks the difference between sham-operated
      and OVX rats was larger (p < 0.05) by QF than by BMD. Moreover, QF correlated
      better than BMD with impact strength and the difference in impact strength
      between sham and OVX mice was closer to that in QF than that in BMD. These data
      demonstrate that QF analysis is a precise technique that is more sensitive than
      DXA in detecting the changes in bone density and strength induced by OVX. QF
      analysis may represent a new, simple, and economic technique for predicting
      fracture risk.

PMID- 9157775
TI  - Effects of intermittent hPTH(1-34) alone and in combination with 1,25(OH)(2)D(3)
      or risedronate on endosteal bone remodeling in canine cancellous and cortical
      bone.
AB  - Therapies utilizing intermittent human parathyroid hormone(1-34) (hPTH[1-34]) in
      combination with other agents have recently been proposed as possible anabolic
      regimens for the treatment of osteoporosis. We conducted a 24 week study in aged
      beagle dogs to determine the effects of intermittent hPTH(1-34) administered
      alone or in combination with 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) on the
      endosteal remodeling in cancellous and cortical bone. Additionally, we tested the
      interaction between hPTH(1-34) and a new potent bisphosphonate, risedronate. The
      three treatment groups were compared with a vehicle control group. Kinetic
      reconstruction of the remodeling unit revealed substantial differences between
      the groups in resorption and formation at the basic multicellular unit level.
      Although the estimates of final erosion depth were unaffected by treatment,
      tunneling resorption was noted in six of the eight dogs administered hPTH(1-34)
      alone. These qualitative morphological changes in the resorption lacunae were
      attenuated or absent in dogs administered hPTH(1-34) in combination with either
      1,25(OH)(2)D(3) or risedronate. Functional periods for resorption were
      significantly increased, and the resorption rates were significantly decreased in
      the hPTH(1-34) + risedronate group. Analyses of the formative site demonstrated
      that the wall thickness was significantly increased and the bone balance
      significantly more positive in all three hPTH(1-34) treatment groups. The most
      positive bone balance was achieved in the combined hPTH(1-34) + risedronate group
      (+ 15.6 + or - 14.2 mm, p <0.05). Increases in the mineral apposition rate in the
      early phases of the formative period suggest that an increase in osteoblastic
      activity (number or function) may contribute to the increase in wall thickness.
      Treatment with hPTH(1-34) alone or in combination with 1,25(OH)(2)D(3) caused an
      approximately 2-fold increase in the activation frequency in cancellous bone,
      which was essentially normalized to control values by the coadministration of
      risedronate. The impact of these changes on the cancellous bone microstructure
      was significant only in the combined hPTH(1-34) + risedronate group where
      normalized bone turnover in the face of a positive bone balance effected a
      significant increase in the trabecular thickness. Analyses of sequential
      fluorochrome labels, administered to reconstruct the temporal changes in
      intracortical activation, demonstrated the presence of an apparent cyclic pattern
      of activation in the cortex of placebo-treated dogs. Generally, activation was
      increased throughout the study in dogs administered hPTH(1-34) alone or in
      combination. However, in the hPTH(1-34) + risedronate group, activation was
      significantly blunted toward the end of the study, and the cyclic pattern of
      activation was modulated. These data suggest that intermittent hPTH(1-34) in
      combination with risedronate may be superior to hPTH(1-34) in combination with
      1,25(OH)(2)D(3) as a therapeutic regimen for osteoporosis due to the protective
      effect of this bisphosphonate on the cortical and endocortical envelope.

PMID- 9157776
TI  - Bone-selective analogs of human PTH(1-34) increase bone formation in an
      ovariectomized rat model.
AB  - Intermittent parathyroid hormone (PTH) therapy increases bone mass. The purpose
      of this study was to determine if analogs of human PTH(1-34) (hPTH[1-34]), which
      differ from the native sequence in their receptor-activating properties, could
      promote bone formation in an ovariectomized (OVX) osteopenic rat model. We
      synthesized two hPTH(1-34) analogs with single substitutions for serine in the 3
      position that in vitro are partial agonists in kidney. In the renal cell line OK,
      maximal cyclic adenosine monophosphate (cAMP) activation by [His(3)]hPTH(134) was
      50%, and maximal cAMP activation by [Leu(3)]hPTH(1-34) was 20% of that produced
      by hPTH(1-34). Both analogs were full agonists in UMR-106 rat osteosarcoma cells
      and other bone-derived systems, but both had reduced potency compared with hPTh(1
      34). Six-month-old retired breeder Sprague-Dawley rats were ovariectomized, and
      five animals underwent sham operation. On day 56 post-OVX, five sham-operated and
      five pre-PTH treatment OVX animals were sacrificed, and the remaining animals
      were randomized into 10 groups of six animals each. All other animals were
      injected with one of the hPTH analogs or hPTH(1-34) at 0, 4, 40, or 400 mu g/kg
      of body weight (BW)/day and were killed on day 84. Histomorphometry of the
      proximal tibia metaphysis and biochemical markers of bone turnover (osteocalcin
      and pyridinoline cross-links) were the primary endpoints. The cancellous bone
      volume was significantly lower at day 56 post-OVX (pretreatment) and at day 84
      post-OVX (post-vehicle treatment) than at baseline. None of the compounds
      significantly increased the cancellous bone volume. Trabecular number declined
      after OVX and did not change with hPTH treatment. In contrast, the trabecular
      thickness declined after OVX but was higher after treatment with 40 mu g/kg of
      BW/day or 400 mu g/kg of BW/day of hPTH(1-34). In OVX rats, the mineralizing
      surface was higher than baseline at day 56 and fell toward control levels by day
      84. All three peptides produced marked dose-related increases in the mineralizing
      surface and bone formation rates, but the two analogs were less potent than
      hPTH(1-34). Likewise, all peptides produced significant dose-related increases in
      the serum osteocalcin level. The osteoclast surface was not affected by OVX but
      was decreased with medium and high doses of hPTH(1-34). Pyridinoline cross-link
      excretion was not significantly affected by treatment with hPTH(1-34) but
      responded with a dose-dependent decrease to treatment with [His3]hPTH(1-34).
      These data suggest that bone selective analogs of hPTH(1-34) maintain the ability
      to induce bone formation but are less potent than hPTH(1-34).

PMID- 9157777
TI  - Dual X-ray absorptiometry quality control: comparison of visual examination and
      process-control charts.
AB  - Dual X-ray absorptiometry (DXA) is widely used to monitor treatment efficacy in
      reducing the rate of bone mineral loss. In order to assure the validity of these
      measurements, instrument quality control of the DXA scanners becomes very
      important. This paper compares five quality control procedures (visual
      inspection, Shewhart chart with sensitizing rules, Shewhart chart with
      sensitizing rules and a filter for clinically insignificant mean changes, moving
      average chart and standard deviation, and cumulative sum chart [CUSUM]) in their
      ability to identify scanner malfunction by means of (1) an analysis of five
      longitudinal phantom data sets that had been collected during a clinical trial
      and (2) an analysis of simulated data sets. The visual inspection method is
      relatively subjective and depends on the operator's experience and attention. The
      regular Shewhart chart with sensitizing rules has a high false alarm rate. The
      Shewhart chart with sensitizing rules and an additional filter for clinically
      insignificant mean changes has the lowest false alarm rate but a relatively low
      sensitivity. The CUSUM method has good sensitivity and a low false alarm rate. In
      addition, this method provides an estimate of the date a change in the DXA
      scanner performance might have occurred. The method combining a moving average
      chart and a moving standard deviation chart came closest to the performance of
      the CUSUM method. Comparing the advantages and disadvantages of all methods, we
      propose the use of the CUSUM method as a quality control procedure for monitoring
      DXA scanner performance. For clinical trials use of the more intuitive Shewhart
      charts may be acceptable at the individual sites provided their scanner
      performance is followed up by CUSUM analysis at a central quality assurance
      center.

PMID- 9157778
TI  - Dual-energy X-ray absorptiometry for histologic bone sections.
AB  - In fundamental osteoporosis research precise and accurate assessment of the
      mineral quantity in histological bone sections is of particular importance when
      studying the local effects of implants releasing bone modulating agents. A
      potentially useful technique to estimate the bone mineral density (BMD) is dual
      energy X-ray absorptiometry (DXA). A highly collimated (0.13 mm) Hologic 2000
      with a line spacing and point resolution of 0.13 mm was used. The mineral content
      was measured in regions of 3.1 mm(2). A ceramic hydroxyapatite (CHA) phantom was
      developed as a reference standard. The phantom was made of a single-phase
      hydroxyapatite starting powder by compressing and sintering at 1000 degrees
      Celsius. The true density was 3.14 + or - 0.001 g/cm(3). The calcium/phosphorus
      ratio was close to the theoretical one of 1.67. The mean precision error
      expressed as the coefficient of variation (CV) of the mineral density (MD)
      measurements of the phantoms with thicknesses of 1, 2, and 3 mm was 0.2%.
      Embedded undecalcified alveolar bone sections of dogs (0.0015-1 mm in thickness)
      were scanned simultaneously with a phantom 1 mm in thickness. The precision error
      (CV) of the BMD measurements calculated by DXA for sections > or = 0.1 mm and
      with a BMD > or = 0.14 g/cm(2) was 0.81%. There was a linear relationship between
      the BMD calculated by DXA and the estimated BMD in the histological bone sections
      by means of the true density of the phantom. It is concluded that DXA using a
      standard CHA phantom is a precise and accurate method to measure MD changes as
      small as 1% in histological bone areas of 3.1 mm(2) provided that the loss or
      gain in BMD is > or = 0.14 g/cm(2).

PMID- 9157779
TI  - Dual-energy X-ray absorptiometry derived structural geometry for stress fracture
      prediction in male U.S. Marine Corps recruits.
AB  - A total of 626 U.S. male Marine Corps recruits underwent anthropometric
      measurements and dual-energy X-ray absorptiometry (DXA) scans of the femoral
      midshaft and the distal third of the tibia prior to a 12 week physical training
      program. Conventionally obtained frontal plane DXA scan data were used to measure
      the bone mineral density (BMD) as well as to derive the cross-sectional area,
      moment of inertia, section modulus, and bone width in the femur, tibia, and
      fibula. During training, 23 recruits (3.7%) presented with a total of 27
      radiologically confirmed stress fractures in various locations in the lower
      extremity. After excluding 16 cases of shin splints, periostitis, and other
      stress reactions that did not meet fracture definition criteria, we compared
      anthropometric and bone structural geometry measurements between fracture cases
      and the remaining 587 normals. There was no significant difference in age (p =
      0.8), femur length (p = 0.2), pelvic width (p = 0.08), and knee width at the
      femoral condyles (p = 0.06), but fracture cases were shorter (p = 0.01), lighter
      (p = 0.0006), and smaller in most anthropometric girth dimensions (p < 0.04).
      Fracture case bone cross-sectional areas (p < 0.001), moments of inertia (p <
      0.001), section moduli (p < 0.001), and widths (p < 0.001) as well as BMD (p <
      0.03) were significantly smaller in the tibia and femur. After correcting for
      body weight differences, the tibia cross-sectional area (p = 0.03), section
      modulus (p = 0.05), and width (p = 0.03) remained significantly smaller in
      fracture subjects. We conclude that both small body weight and small diaphyseal
      dimensions relative to body weight are factors predisposing to the development of
      stress fractures in this population. These results suggest that bone structural
      geometry measurements derived from DXA data may provide a simple noninvasive
      methodology for assessing the risk of stress fracture.

PMID- 9157780
TI  - Expression of rat bone sialoprotein promoter in transgenic mice.
AB  - Bone sialoprotein (BSP) is a major protein of the mineralized bone extracellular
      matrix that has been implicated in the nucleation of hydroxyapatite crystals. Our
      previous studies have demonstrated that BSP mRNA is expressed by differentiated
      osteoblasts, odontoblasts, and cementoblasts involved in de novo mineralized
      tissue formation in a tissue-specific and developmentally regulated manner. To
      determine the basis of the selective expression of the BSP gene, we have
      generated four transgenic mouse lines in which 2.7 kb of the rat BSP promoter
      ligated to a luciferase reporter gene has been stably integrated into the mouse
      genome. Assays of luciferase activities in 5-day-old animals has revealed
      consistently high levels in bone tissues with negligible activities in various
      other organs including kidney, liver, stomach, intestine, and spleen. In some
      animals, variable expression was observed in brain and skin. Temporal analyses
      revealed the highest luciferase expression in neonatal bones, with expression
      decreasing markedly with subsequent growth and development, as observed
      previously for the endogenous gene in rats. Immunohistochemical analysis of
      luciferase activity and in situ hybridization of luciferase mRNA in bone tissues
      show that differentiated osteoblasts express the highest levels of luciferase,
      consistent with the induction of endogenous gene expression. These studies
      demonstrate that the regulation of the BSP gene during osteoblastic
      differentiation, together with its tissue-specific, developmentally regulated
      expression, is primarily mediated within the 2.7 kb region of the promoter.

PMID- 9157781
TI  - Bone sialoprotein expression in primary human breast cancer is associated with
      bone metastases development.
AB  - Breast cancer metastasizes to bone more frequently than to any other organ, and
      over 80% of advanced breast cancer patients develop bone metastases. Our recent
      demonstration that human breast cancer cells express bone sialoprotein (BSP), a
      bone matrix protein, provides a possible clue for the selective affinity of
      breast cancer cells for bone. We tested the hypothesis that detection of BSP in
      primary human breast cancer could be a potential indicator of the ability of
      breast cancer cells to metastasize to bone. BSP expression was evaluated in the
      primary breast cancers of 39 patients using immunoperoxidase and two specific
      anti-BSP antibodies. None of these patients presented clinically or
      scintigraphically detectable bone metastases at the time of surgery. In the
      course of their disease, 22 patients developed clinically diagnosed bone
      metastases. Expression of BSP in breast cancer cells from patients who developed
      bone metastases was significantly higher (p = 0.008, according to the Mann
      Whitney test) than in patients with no bone involvement. No association was found
      between BSP expression in the primary breast lesions and axillary lymph node
      metastases. BSP expression was significantly increased in infiltrating ductal
      carcinoma compared with infiltrating lobular carcinoma (p = 0.0023). No
      correlation was found between immunoreactivity to BSP antibodies and estrogen
      receptor (ER) status, progesterone receptor (PR) status, or age. Our data suggest
      that BSP could help to identity which women will develop bone metastases and
      provide new bases for the understanding of the molecular mechanism(s) responsible
      for breast cancer cells osteotropism.

PMID- 9157783
TI  - Altered trabecular architecture induced by corticosteroids: a bone
      histomorphometric study.
AB  - Prolonged corticosteroid (CS) therapy induces osteoporosis and fractures.
      Osteoporosis is characterized at the histomorphometric level by reduced bone
      volume (BV/TV) and disruption of the three-dimensional (3D) trabecular
      architecture. Several stereological methods have been proposed to characterize
      these alterations: measurements of trabecular thickness and trabecular number,
      star volumes, interconnectivity index (ICI) of the bone marrow spaces, and
      trabecular bone pattern factor (TBP(f)). These methods were computerized with a
      single program running on an image analyzer to evaluate the bone changes in a
      series of iliac biopsies performed on 31 male patients. All of them were
      asthmatic and had received CS for a long period of time. BV/TV was reduced when
      compared with age-matched controls. In the CS-treated population, exponential
      relationships were obtained between bone volume and the different connectivity
      parameters. The various methods used to measure connectivity were well
      correlated. When the population was divided into two groups (BV/TV greater or
      less than an 11% threshold), the architectural disturbances were found to imply
      two mechanisms. A progressive decline in trabecular thickness was noted in both
      groups versus controls. Trabecular perforations were not established in the group
      with BV/TV> 11% with the star volume or ICI, although some alterations were
      detected by trabecular bone pattern factor measurement. However, perforations
      were revealed in the group with BV/TV < 11% by all the different methods.
      Perforations seemed to occur when the trabecular thickness was below 70 mu m.
      This strongly suggests that bone histomorphometry should take into consideration
      bone volume in combination with detailed 3D descriptors of the trabecular
      architecture. Several histological methods need to be used in combination to
      appreciate the 3D architecture of trabecular bone.

PMID- 9157782
TI  - Osteoclastic superoxide production and bone resorption: stimulation and
      inhibition by modulators of NADPH oxidase.
AB  - Production of superoxide radicals by osteoclasts is necessary for normal bone
      degradation. White blood cell superoxide, needed for bacterial killing, is
      produced by activated NADPH oxidase. Since osteoclasts and white blood cells
      share a common hematopoietic origin, we initiated experiments to test the
      hypothesis that superoxide radicals at the osteoclast-bone interface are produced
      by NADPH oxidase. Diphenyl iodonium (IDP), an inhibitor of NADPH oxidase, blocked
      superoxide generation and decreased osteoclastic bone resorption in cultures of
      calvarial explants from normal mice. Interferon (IFN) gamma, a stimulant of NADPH
      oxidase activity, increased superoxide production and bone resorption in cultures
      of calvarial explants from osteopetrotic (microphthalmic) mice. IDP blocked the
      stimulatory effects of IFN in this bone resorption model. These data suggest that
      osteoclastic superoxide is produced by NADPH oxidase.

PMID- 9157784
TI  - Characterization of a collagenous cementum-derived attachment protein.
AB  - We report further characterization of a cementum-derived protein that promotes
      the adhesion and spreading of periodontal cells. The cementum attachment protein
      (CAP) was extracted from bovine cementum, separated by diethylamino ethyl (DEAE)
      cellulose chromatography, and purified by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis and C18 reverse phase high performance liquid chromatography.
      The purified preparation contained a single protein band migrating with M(r)
      56,000. It did not cross-react with polyclonal antibodies to osteopontin,
      vitronectin, or other attachment proteins. The attachment activity was resistant
      to chondroitinase ABC digestion. An internal amino acid sequence of six peptides
      was determined by microsequencing, and the peptide sequences were not present in
      other attachment proteins described in cementum. Four sequences contained Gly-X-Y
      repeats typical of collagen helix. One 17 amino acid peptide had 82% homology
      with a type XII collagen domain. However, bovine type XII collagen did not
      promote fibroblast attachment. Although another 19-amino-acid-long peptide had
      95% homology to bovine alpha 1 [I], two other peptides were only 74% and 68%
      homologous, and the CAP was not recognized by anti-type I collagen antibody. The
      attachment activity of CAP was susceptible to bacterial collagenase. The CAP did
      not cross-react with antibodies to type V, XII, and XIV collagens. These data and
      our previous immunostaining data indicate that the CAP is not related to other
      collagens or attachment proteins and that it is a collagenous attachment protein
      localized in cementum.

PMID- 9157785
TI  - Unilateral hip replacement causes bilateral changes in tibial bone mineral
      content in a canine model.
AB  - The presence of asymmetry in tibial bone mineral content (BMC) of the operated
      and control limbs at the end of the experimental period following unilateral hip
      replacement surgery is used as a marker of limb function. The goal of the present
      study was to determine the contribution of ipsilateral and contralateral bone
      gain and loss to control-treated side differences in BMC of the tibia in dogs
      following unilateral hip replacement surgery. Seven animals were followed
      longitudinally with single beam photon absorptiometry for 6 months after
      unilateral hip hemiarthroplasty. Bone loss, compared with preoperative baseline
      values, was observed in both limbs, with recovery in bone mass beginning 1 month
      after surgery in the contralateral tibia and 3 months after surgery in the
      ipsilateral tibia. Thus, the asymmetry in tibial BMC frequently seen after
      unilateral experimental hip replacement in the canine appears to be caused by
      differential timing of recovery of bone mass following a transient loss in both
      limbs. The mechanism defined in this study is in contrast to an alternative
      mechanism involving bone loss in the treated limb coupled with bone gain in the
      control limb.

PMID- 9157786
TI  - Osteomalacia and osteoporosis in a woman with ankylosing spondylitis.
AB  - Three months postpartum, a 33-year-old woman with ankylosing spondylitis (AS)
      suffered multiple vertebral fractures. Bone mineral density was 61-67% of age
      matched normal values at the lumbar spine and proximal femur, and an initial
      iliac crest bone biopsy revealed osteoporosis and osteomalacia. Secondary causes
      of bone disease were excluded, and the patient was treated with calcium, vitamin
      D, and nasal spray calcitonin (400 u/day). Over 4 years, she has shown partial
      recovery of bone mass and almost complete resolution of osteomalacia.
      Osteoporosis and fracture occur in patients with AS, yet this case represents a
      rare association between AS and both osteomalacia and postpregnancy spinal
      osteoporosis.

PMID- 9157787
TI  - What's good for the heart is not good for the bones?

PMID- 9157788
TI  - Reproductive Health, a Human Right and a Pillar of Human Dignity. Proceedings of
      a symposium in celebration of the 75th birthday of Professor Egon Diczfalusy.

PMID- 9157789
TI  - Report of the American Medical Student Association's Nutrition Curriculum
      Project. Essentials of nutrition education in medical schools: a national
      consensus.
AB  - Medical students of the American Medical Student Association established the
      Nutrition Curriculum Project (NCP) with the goals of ensuring that adequate
      nutrition information be taught to medical students; ensuring that there be a
      framework for integration of nutrition topics at all levels of medical education;
      and formulating and disseminating essential information for nutrition assessment
      and management in clinical practice. As a first step, the NCP assembled a ten
      member advisory board to develop a comprehensive list of nutrition topics deemed
      essential for the adequate training of physicians. The advisory board consisted
      of medical and nutrition educators, physicians, and clinical specialists
      representing major U.S. professional nutrition organizations. The NCP's director
      coordinated the decision-making process through its three iterations. Final
      accord on 92 topics was achieved with unanimous approval of the board in 1994.
      These topics, organized in five major categories, are offered as a guide to the
      reform of nutrition education and as the basis of a satisfactory nutrition
      curriculum.

PMID- 9157790
TI  - Credentials available in human clinical nutrition: a report of the Intersociety
      Committee on Nutrition Certification.

PMID- 9157791
TI  - Proceedings of the workshop on individual fatty acids and cardiovascular disease.
      Washington, DC, USA, March 30-31, 1995.

PMID- 9157792
TI  - Blindsight and consciousness.
AB  - Implications for understanding consciousness are considered by focusing on two
      behaviors whose mutual disparity indicates blindsight. Among the topics are: (a)
      the basis on which people report seeing something in particular; (b) two
      interpretations of blindsighted subjects' forced-choice guessing as affected by
      perceptual judgments outside subjects' awareness or as based on "pure perceptual
      knowledge" of which subjects have awareness, though this "knowledge" is
      nonconsciously acquired; (c) whether blindsight is "behavior divorced from
      awareness"; and (d) an interpretation of blindsight as a matter of responding to
      internal occurrences.

PMID- 9157793
TI  - Experimental Morphology, the 1st International Symposium. Sofia, May 24-26, 1996.
      Abstracts.

PMID- 9157794
TI  - [Genetic events and molecular biology of Wilms' tumor].

PMID- 9157795
TI  - [Subject: "Levothyroxine". The thyroid working group of the Spanish Society of
      Pediatric Endocrinology].

PMID- 9157796
TI  - [Sun and skin cancer. Role of the pediatrician].

PMID- 9157797
TI  - [Is there a relationship between vaccination coverage and pediatric health
      care?].
AB  - OBJECTIVE: The aims of this study were to evaluate the relationship between
      pediatric health care visits and immunization coverage. PATIENTS AND METHODS: The
      study was made in a rural health care center. All of the children between 3
      months and 14 years old were included. The data were obtained directly from their
      clinical histories. The quality of the health care visits was evaluated according
      to the fulfillment of A.E.P. patterns of health care. RESULTS: We observed that
      87% of infants, 74% of preschool children and 74% of school children were
      correctly vaccinated. We observed a significantly lower (p < 0.05) coverage of
      the MMR vaccine in respect to the first three doses of DPT and OPV vaccines; and
      the coverage of OPV and DT at 6 years old was even lower. The quality of health
      care visits was good in 67% of infants, 10% of preschool children and 12% of
      school children. There was a relationship between incomplete vaccinations and
      missed visits (p < 0.001) and also with low quality health care visits (p <
      0.001). CONCLUSIONS: We conclude that there is a significant relationship between
      missed visits and low quality health care visits with delayed immunization.

PMID- 9157798
TI  - [Physical activity and leisure time in children. I: Relation to socioeconomic
      status].
AB  - OBJECTIVE: To assess physical activity and leisure time activities in relation to
      socioeconomic status. PATIENTS AND METHODS: We have studied 1,078 boys and girls
      from 24 schools from areas of different geographical and socioeconomical status.
      Physical activity and leisure time activities were assessed by a questionnaire.
      RESULTS: We have observed that adolescents spend more time watching T.V. than
      doing physical activity (p = 0.0001). In general, boys prefer strong physical
      activity. Children from the lowest socioeconomic families did less physical
      activity than children from the highest socioeconomic families (p < or = 0.05).
      In girls, those with the lowest socioeconomic status spent the greatest amount of
      time watching T.V. (p = 0.0001). CONCLUSIONS: From our results, we deduce that we
      must improve physical activity habits in children, especially in those from the
      lowest socioeconomic families.

PMID- 9157799
TI  - [Physical activity and leisure time in children. II: Relationship with dietary
      habits].
AB  - OBJECTIVE: To investigate the relationship between physical activity, leisure
      time activities and dietary habits in adolescents. PATIENTS AND METHODS: We have
      studied 541 girls and 537 boys from 24 schools. Physical activity, leisure time
      activities and dietary habits were assessed by 3 different questionnaires, taking
      into account one week of normal activity and diet. RESULTS: Foods such as milk,
      fish, meat, egg, fruits, vegetables, pasta and snacks were consumed more
      frequently in children who spent more time doing sport, but difference were not
      statistically significant. Boys who spent more time watching T.V. ate greater
      amounts of almost all foods (p < 0.05). In girls, we have observed the same
      results, but differences were not statistically significant. CONCLUSIONS: Sports
      and T.V. watching are both related to a greater amount of food intake From our
      results we can deduce that in order to prevent obesity, and other cardiovascular
      risk factors, we must improve food intake related with sedentary habits.

PMID- 9157800
TI  - [Back pain in children].
AB  - OBJECTIVE: The incidence of back pain in children in our country is unknown.
      Several causes can produce this symptom, but it is necessary to rule out
      pathologies that require specific treatments. The goal of this work was to study
      the incidence and the etiology of back pain in children in our country. PATIENTS
      AND METHODS: We present a prospective study done in our Orthopedic Department
      during a period of 7 months. Twenty-two patients were referred with back pain of
      at least two months duration. The incidence was 2.9% compared to the total number
      of patients. The average age ranged from 7 to 17 years. RESULTS: A careful
      history and a radiological examination diagnosed 50% (11 cases) of the causes of
      backache in the present study. An idiopathic etiology was the most frequent cause
      and represented 9 patients (41%). In the remaining 12 cases (59%) pathological
      causes that required special treatment were identified including 2 cases of
      Scheuermann disease, 4 cases of painful scoliosis, 3 spondylolysis with
      spondylolisthesis, 2 cases of discitis, 1 benign neoplasm and 1 psychogenic
      cause. CONCLUSIONS: We recommend conservative management with the use of
      medication for relief of pain and physical therapy in the idiopathic cases. In
      the remaining cases, the specific treatment of the disease can improve the back
      pain.

PMID- 9157801
TI  - [Sturge-Weber syndrome: experience with 14 cases].
AB  - OBJECTIVE: The objective of this study was to review the cases of Sturge-Weber
      syndrome (SWS) diagnosed and followed-up in our center over the last 25 year
      period in order to evaluate their clinical characteristics, evolution and
      therapeutical response. PATIENTS AND METHODS: A retrospective review of the
      records of patients diagnosed of SSW (facial nevus flammeus at least over the
      first branch of the trigeminal nerve and ipsilateral leptomeningeal angioma) was
      performed. RESULTS: Fifteen patients were found in our records, with one of them
      being excluded from the study due to the lack of follow-up. From the remaining
      14, 11 had been diagnosed before the age of 18 months. Nevus flammeus was located
      on the right side in 8 cases, bilaterally in 3 and on the left side in the other
      3 patients. Four cases had glaucoma, 3 of which had good evolution after
      trabeculotomy. Thirteen of the 14 patients had seizures, usually contralateral to
      the nevus flammeus. The main drugs used were phenytoin, phenobarbital, valproic
      acid and carbamazepine. Ten of the 13 patients treated had a good therapeutical
      response. The EEG was abnormal in 12 patients, two of them occurring during the
      follow-up period. The main abnormality found was an interhemispherical asymmetry.
      Nine patients developed hemiparesis. In reference to the neuroimaging. MR was
      better than CT in evaluating parenchymatous atrophy, which was present in all
      patients, and the abnormalities of the white and grey matters (9 and 8 patients,
      respectively). CONCLUSIONS: Early evaluation of newborns with nevus flammeus
      affecting the first branch of the trigeminal nerve must be done, including an MR
      with contrast and an ophthalmological exam.

PMID- 9157802
TI  - [Bronchiolitis: revision of 153 cases and comparative study of ribavirin
      treatment].
AB  - OBJECTIVE: We try in this paper to improve the knowledge of the main
      epidemiological, clinic, evolutive and therapeutic data in cases of children
      suffering from bronchiolitis in our medium; we analyze particularly the possible
      usefulness of ribavirin as a causal treatment. MATERIAL AND METHODS: Firstly we
      have accomplished backward studies about the children suffering from
      bronchiolitis, who has been hospitalized in our Unit from January 1987 to May
      1994. Then we have carried out a comparative study of the evolution in both
      groups of patients with and without RBV treatment. We have identified the
      Respiratory Sincityal Virus (RSV) by direct immunofluorescence. RESULTS: We have
      found that the bronchiolitis impact is much higher during the winter, as well as
      city areas. The more affected patients are significantly younger than those with
      less severe injuries (p < 0.0005), and then, often show personal antecedent of
      prematurity and neonatal respiratory pathology. We have identified the RSV in
      90.8% of the patients. The group treated with RBV showed a significative
      improvement of respiratory distress. The final cost of treatment was very similar
      in both groups (with and without RBV), since the hospital stay was shorten in the
      ribavirin group. CONCLUSION: RBV treatment was very usefull in moderate as well
      as severe cases in wich we found in average, a significative improvement of the
      clinic sign of respiratory distress.

PMID- 9157803
TI  - [Family prevalence of idiopathic scoliosis].
AB  - OBJECTIVE: Review of the literature shows that, for the moment, the cause of
      idiopathic scoliosis remains unknown. It has been attributed to a wide variety of
      conditions, including genetics. The aim of this paper was to determine the
      frequency of antecedents and family prevalence of idiopathic scoliosis in first
      and second degree relatives. PATIENTS AND METHODS: During 1994-1995, the
      families, including first and second degree relatives, of 100 schoolchildren with
      idiopathic scoliosis were surveyed for scoliosis. The screening was done
      initially by clinical examination, the test of Adams and subsequently the
      diagnosis was confirmed by roentgenography. RESULTS: Our study showed the
      following results. Twenty-five percent of patients investigated had one or more
      affected individuals in their family. Prevalence of idiopathic scoliosis in first
      degree relatives was 5.16% and in second degree relatives 4.31%. It was more
      frequent in females than in males (p < 0.05). This prevalence is larger than that
      in the general population (1-2%). CONCLUSIONS: Our conclusion is that the
      mechanism of inheritance is most likely multifactorial. In view of the
      predominance of females, an X-linked inheritance is suggested.

PMID- 9157804
TI  - [Bacteremia during the course of Salmonella gastroenteritis].
AB  - OBJECTIVE: Salmonella is the most frequent cause of bacterial acute
      gastroenteritis (AGE) in our setting. Usually its course is self-limited, but it
      sometimes can lead to bacteremia, principally in young infants and malnourished
      or immunosuppressed children. Bacteremia is less frequent in healthy people and
      in those over one year of age. This study was carried out to assess the incidence
      of bacteremia during Salmonella GE and to detect parameters that could lead to
      bacteremia. PATIENTS AND METHODS: A retrospective study of positive stool
      cultures in our hospital between 1991 and 1993 was performed. Data about the
      epidemiology, clinical features cultures and analytical procedures were drawn
      from clinical records. Data were analyzed using the Mann-Whitney test and
      Fisher's exact test. RESULTS: During this period of time, 860 cases of AGE were
      observed with 86 stool cultures positive for Salmonella (10%). Six of them also
      had positive blood cultures (7%). All 6 patients with bacteremia were healthy
      previously and five were over 12 months old. The outcome was good in all cases,
      without focalizations of the bacteremia. We could not detect any differences
      between patients with positive blood cultures and the patients without
      bacteremia. CONCLUSIONS: Bacteremia during Salmonella AGE is not infrequent and
      is not limited to young infants or patients with underlying diseases. None of the
      parameters analyzed were useful in predicting the possibility of bacteremia.

PMID- 9157805
TI  - [Hyperamylasemia after cardiac surgery in children].
AB  - OBJECTIVE: To analyze the incidence of hyperamylasemia after cardiac surgery in
      children, the pathogenic mechanisms and the relationship with morbidity and
      mortality. PATIENTS AND METHODS: A prospective open study was made in the
      Intensive Care Unit of a tertiary care pediatric hospital. One hundred thirty-one
      patients (75 boys and 56 girls), between 7 days and 16 years of age, were studied
      after cardiac surgery between 1992 and 1994. We determined serum amylase on their
      admission, at 24 hours, between the 2nd and 5th days, and thereafter according to
      the clinical evolution. We considered a serum amylase higher than 250 UI/L as
      hyperamylasemia. We also determined liver enzyme levels (AST, ALT, Gamma-glutamyl
      transpeptidase, alkaline phosphatase, and direct and total bilirubin) and renal
      function (urea and creatinine). We studied the relationship between
      hyperamylasemia and the type of surgery, shock, renal insufficiency, hepatic
      alterations and mortality. RESULTS: Fourteen patients (10%) showed
      hyperamylasemia. Mean serum amylase in these patients was 534 +/- 332.6 UI/L
      (range 252-1426 UI/L). Of the patients were cardiopulmonary bypass was performed,
      11.4% presented hyperamylasemia, and 8.5% of the patients without a
      cardiopulmonary bypass surgery (non-significant difference). Of the children with
      hyperamylasemia, 42.8% suffered shock during the postoperative period after
      cardiac surgery and only 15.2% of the rest of the patients (p < 0.05). There were
      no differences in the incidence of renal insufficiency and liver alterations
      between children with hyperamylasemia and the rest of the patients. There was no
      significant difference between the mortality of children with hyperamylasemia
      (7.1%) and the rest of the children (4.7%; p > 0.05). CONCLUSIONS:
      Hyperamylasemia is frequent after cardiac surgery in children. Hyperamylasemia is
      related to shock and the ischemia is probably the most pathogenic factor.

PMID- 9157806
TI  - [Idiopathic hypercalciuria: clinical manifestation, outcome and risk for
      urolithiasis in children].
AB  - OBJECTIVE: The purpose of this study was to investigate the clinical
      manifestations, outcome and risk factors for urolithiasis of untreated idiopathic
      hypercalciuria (IH) in children. PATIENTS AND METHODS: During a 5 year period,
      all children with hematuria, lower urinary tract symptoms (LUS), or abdominal
      pain who were observed to have IH (urinary calcium > 4 mg/kg/day) were included
      in the study. The relationship between some variables (age, gender,
      hypercalciuria subtype, and clinical features) and urolithisis was analyzed.
      RESULTS: We studied 76 children with IH (9 with renal IH, 49 with absorptive IH
      and 18 with undetermined IH). Hematuria (46%), LUS (27.6%), lumbar pain (22%) and
      abdominal pain (15.7%) were the most common initial symptoms. We found a
      significant difference between age and clinical presentation. LUS were found more
      frequently in young children (46.4%) and flank pain in older patients (47.8%).
      Hematuria was age dependent. Eighteen (23%) patients developed urolithiasis.
      These 18 patients tended to be older (9.3 vs 6 years) than the other 58 children.
      Age at diagnosis presented a linear relationship with the development of
      urolithiasis (p < 0.001). Significant relative risk for urolithiasis (4.3) was
      found in those children who initially presented with lumbar pain. In all other
      parameters measured (calciuria, uricosuria, oxaluria, citraturia) and clinical
      characteristics analyzed, there were no statistically significant differences
      between those with and without stones. CONCLUSIONS: An age-dependent clinical
      pattern can be established for children with hypercalciuria. Significant risk for
      urolithiasis accompanies those children who are diagnosed later (> 9 years) and
      who initially present with lumbar pain.

PMID- 9157807
TI  - [Serum TSH values during clinical controls of patients treated for congenital
      hypothyroidism].
AB  - During the second half of 1995, an increased serum TSH level was found in about
      50% of the patients that had been biochemically studied to check their treatment
      for hypothyroidism by the Laboratory of Molecular Endocrinology in the Regional
      Hospital of Malaga. A retrospective analysis was carried out to check if those
      results were erroneous. The biochemical data concerning the thyroid function were
      followed-up in patients requiring more studies, such as the ones suffering from
      congenital hypothyroidism (CH) and a random double assay of some samples was made
      with an alternative technique. Currently, the average TSH level is rated as 14.31
      microU/ml in 54% of the subjects, even though levothyroxine doses were increased.
      Levothroid is the preparation prescribed in all cases. In 1994, the TSH average
      level was 1.68 microU/ml in the aforementioned group. Another 12% with increased
      TSH levels were readjusted by modifying the treatment. The T4F in CH subjects
      with increased TSH dropped significantly from 24.1 pmol/ml to 15.7 pmol/ml in the
      same period of time. We suggest that one possible etiological factor could be a
      mistake in the dosage of the commercial preparation.

PMID- 9157808
TI  - [Standardization of the Kent Infant Development Scale: implications for primary
      care pediatricians].
AB  - OBJECTIVE: The purpose of this study was the standardization of an infant
      assessment protocol based on behavioral observations of Spanish parents. The Kent
      Infant Development (KIDS) scale was translated into Spanish and named "Escala de
      Desarrollo Infantil de Kent" (EDIK). PATIENTS AND METHODS: The EDIK normative
      data were collected from the parents of 662 healthy infants (ages 1 to 15 months)
      in pediatric clinics. Infants born more than 2 weeks premature or who had serious
      physical or neurological illness were not included. RESULTS: EDIK raw scores of
      Spanish infants were converted to developmental ages by comparing them with the
      number of behaviors for each age group in the normative sample. We obtained the
      mean score and standard deviation for the full scale and different domains
      (cognitive, motor, social, language, and self-help). CONCLUSIONS: This study
      shows that EDIK is sensitive to differences in ages and a good instrument that
      allows one to make a classification between normal infants or those at risk. It
      should prove useful in developmental pediatric practice.

PMID- 9157809
TI  - [High frequency oscillatory ventilation in the preterm newborn infants with
      respiratory distress syndrome].
AB  - OBJECTIVE: The objective of this study was to evaluate the efficiency and
      response of gas exchange by the use of high frequency respiratory modalities in
      cases rescued after failure of conventional mechanical ventilation. PATIENTS AND
      METHODS: A retrospective study of twelve premature infants that required high
      frequency ventilation (HFV) as rescue therapy for treatment of respiratory
      distress syndrome (RDS) because of failure of conventional mechanical ventilation
      (CNV) were studied. The mean weight and gestational age were 1,041 gr (500-1,730)
      and 28 weeks (26-34), respectively. Fifty percent of the infants weighed less
      than 1,000 grams. Two different respiratory apparatus were used. Five infants
      were treated using Infant Star and seven with Babylog 8000. The variables were
      analyzed by comparison of the means with significance taken as p < 0.05. RESULTS:
      High frequency ventilation was initiated at 24 hours of life (2-86) and the mean
      duration was 33 hours (1-133). We saw a significant improvement in oxygenation
      after starting HFV and during the first and second controls after HFV initiation.
      PaO2 increased from 59 mmHg to 87 (HFV-initial), 119 mmHg (HFV-first control) and
      98 mmHg (HFV second control; p < 0.05). Likewise, a/AO2 increased from 0.087 to
      0.13 (HFV-initial), 0.19 (HFV-first control) and and 0.18 (HFV-second control; p
      < 0.05). The oxygenation index (OI) decreased from 23 to 16 (HFV-initial p <
      0.05) and to 11 during the first and second controls (p < 0.01). Despite the
      improvement in oxygenation, there were no differences in mean airway pressure
      levels. We did not see any change in PaCO2 levels. The mortality rate was 58%,
      with a mean age at death of 82 hours of life (6-264). CONCLUSIONS: High frequency
      ventilation might be used as a rescue therapy for treatment of respiratory
      distress syndrome since there is an improvement in oxygenation.

PMID- 9157810
TI  - [High frequency oscillatory ventilation in the newborn infant].
AB  - OBJECTIVE: The objective of this study was to determine the effectivity, results
      and complications after application of HFOV in a group of newborns with serious
      respiratory distress. PATIENTS AND METHODS: Between February and October 1995,
      HFOV was required by 18 newborns in the NICU of the Hospital "La Fe" of Valencia,
      as ventilatory rescue therapy because of the failure of conventional ventilation
      in 10 cases (group A) and serious air leaks in 8 cases (group B). We used pure
      HFOV without superimposed cycles of conventional IMV following a high volume-high
      pressure strategy. Among the lung pathology, RDS was most frequent (11/18).
      RESULTS: Twenty-four hours after beginning HFOV, a decrease of the FiO2 was
      obtained in group A from 0.89 to 0.4 and in group B from 0.7 to 0.4. Oxygenation,
      ventilation, OI and a/AO2 ration also improved. In the group with conventional
      ventilation failure, this improvement was significant for all parameters in the
      first two hours after the start of HFOV (p < 0.01). In the group with air leaks,
      all parameters improved at two hours, but this change was significant only for
      oxygenation (p < 0.01). Four newborns died (22%) in the first month. CONCLUSIONS:
      HFOV is an effective and secure ventilatory method when conventional ventilation
      fails or serious air leaks occur. Important improvement in oxygenation and
      ventilation is obtained during the first two hours and it is possible to decrease
      the oxygen requirements at 24 hours after the start of HFOV.

PMID- 9157812
TI  - [ Osteofibrotic dysplasia of the long bones versus ossifying fibroma].

PMID- 9157811
TI  - [Neonatal meningitis: study of 56 cases].
AB  - OBJECTIVE: The objective of this study was to know the most common organisms
      causing neonatal meningitis in a defined region of southern Madrid, the
      developmental outcome of these babies and the risk factors associated with the
      prognosis. PATIENTS AND METHODS: This was an observational study of 56 cases of
      meningitis diagnosed in our Neonatal Service between 1988 and 1994. In order to
      study the handicaps of these babies, only those who were born before May 1993
      were considered so that they had a corrected age of at least 2 years when the
      neurological evaluations were done. RESULTS: The most common causative organisms
      were group B Streptococcus (27%), E. coli (11%) and enteroviruses (9%). In the
      premature infants the leading organisms were E. coli and Candida albicans. The
      age at diagnosis was 8 +/- 6 days in the group of preterm infants (p = 0.002).
      The mortality was associated with the prematurity (risk ratio: 17.8), the
      isolation of a gram-negative organism in the cerebral fluid (RR: 3.3) and the
      presence of abnormal findings in cerebral ultrasound studies (RR: 12.7). Sequelae
      were associated with the presence of abnormal findings in cerebral ultrasound
      studies (RR: 24.7) or in the neurologic examination (R: 7) and with the presence
      of previous cerebral lesions (RR: 5.7). CONCLUSIONS: Neonatal ultrasound
      examination, as well as the gestational age, the causative organisms, the
      presence of a previous cerebral lesion and the neurological examination, seem to
      be very important in predicting the prognosis of these babies.

PMID- 9157813
TI  - [Meningitis due to beta-lactase resistant pneumococcus: presentation of two
      cases].

PMID- 9157814
TI  - [Digital ischemia of the lower limb: reversion via sympathetic blockage].

PMID- 9157815
TI  - [An immunodepressed girl with acute bilateral pneumopathy].

PMID- 9157816
TI  - [Lasers in urology].

PMID- 9157817
TI  - [Laser-tissue interactions in urology].
AB  - The laser-tissue interaction is a complex phenomenon which is usually classified
      into 4 distinct mechanisms: electro-mechanical action, photoablative action,
      thermal action and photochemical action. Fragmentation of calculi by means of a
      pulsed dye laser is a good example of the electro-mechanical action. The thermal
      action can induce coagulation and/or volatilisation of tissues. Treatments of
      bladder tumors, urethral strictures and more recently benign prostatic
      hypertrophy are based on the laser terminal action.

PMID- 9157818
TI  - [Laser treatment of benign prostatic hypertrophy: the correlation of histologic
      results to nuclear magnetic resonance imaging].
AB  - Minimally invasive treatments for benign prostatic hyperplasia (BPH) are
      currently very controversial. Nd:YAG laser transurethral thermocoagulation of the
      prostate is the technique most frequently used. The objective of this study was
      to assess the correlation between the morphological effects observed and the
      changes visible on magnetic resonance imaging during this type or treatment in
      the human prostate, in order to evaluate the tissue effects obtained according to
      the power and the interaction time applied. In 10 patients requiring radical
      prostatectomy for urological cancer, visual laser ablation of the prostate (VLAP)
      was performed during the 10 days preceding the radical operation (range: 1 to 9
      days). The entire gland was submitted to pathological examination in order to
      correlate the histological result with contrast magnetic resonance imaging
      performed in 6 patients, using a standard transrectal coil, 12 to 24 hours before
      complete resection of the prostate. The morphological examination showed zones of
      periurethral necrosis of variable volume, accompanied by extensive peripheral
      haemorrhage, containing vessels with a partially obliterated lumen. Contrast
      magnetic resonance imaging (T1) showed that laser-induced lesions had a low
      density appearance and were perfectly demarcated with peripheral heterogeneous
      and hyperdense zones. In contrast with the experimental investigations performed
      to date, we demonstrated a clearly delayed tissue effect. Our experience
      demonstrates that a period of several hours between laser treatment and removal
      of the operative specimen is not sufficient to evaluate the extent of laser
      induced lesions. High resolution magnetic resonance imaging with a standard
      transrectal coil, sometimes combined with a multiple coil, is very valuable to
      assess the effects of laser.

PMID- 9157819
TI  - [Laser thermocoagulation of adenoma of the prostate using an interstitial
      approach].
AB  - Interstitial laser coagulation (ILC) is a minimally invasive treatment for benign
      prostatic hyperplasia (BPH). The objective of ILC is to induce shrinking of the
      prostate while preserving all surrounding tissues. To achieve thermal coagulation
      well inside the adenoma, not at its urethral surface, laser radiation of a Nd:YAG
      laser or a diode laser is transmitted by specially designed laser fibers
      repeatedly placed in the prostate tissue. This results in secondary atrophy and
      regression of the prostate lobes, not sloughing of necrotic tissue. Since, July
      1991, more than 800 patients have been treated in several studies. Based on
      initial experiences, many technical and procedural improvements of ILC have been
      introduced for clinical use, such as advanced radiation programs and new
      application devices including optical feedback systems. Imaging studies
      demonstrated treatment effects and allowed further treatment optimization.
      Clinical studies have demonstrated the safety and efficacy of ILC. This review
      summarizes several articles published on ILC and reports initial results of
      ongoing studies comparing ILC and transurethral resection of the prostate (TURP).

PMID- 9157820
TI  - [Vaporization of urethral stenosis using the KTP 532 laser].
AB  - The authors treated 16 patients presenting with a total of 20 anterior urethral
      strictures using the KTP 16 Laser. The aetiology was iatrogenic in 50% of cases,
      infectious in 20% of cases, traumatic in 20% of cases and unknown in 10% of
      cases. The stricture was situated in the bulbous urethra (80%), membranous
      urethra (10%) or penil urethra (10%). Laser vaporization of the urethral
      stricture was performed over the entire circumference of the urethra when
      necessary, followed by bladder drainage by urethral catheter for 24 hours. All
      patients were prospectively reviewed at 3 weeks, 3 months and 6 months (clinical
      symptoms, uroflowmetry, cystourethrography). A complete symptom and urodynamic
      success was obtained in 13 patients (81%) at 3 and 6 months. The stricture
      recurred in 4 patients, but only three of them (19%) required treatment
      (reoperation of repeat dilatations). The mean maximum flow rate increased from 6
      mL/s to 20 mL/s at 3 months and was maintained at 19 mL/s at 6 months. No
      intraoperative or postoperative complications were observed. In conclusion, our
      results confirm that KTP 532 laser urethral strictures is a reliable and
      effective method in the medium term. These good results also suggest an advantage
      in terms of the recurrence rate in comparison with internal urethrotomy. However,
      our series needs to be evaluated with a longer follow-up and prospective,
      randomized trials comparing the two methods need to be conducted.

PMID- 9157821
TI  - [The clinical value of fluorescence cystoscopy in the detection of superficial
      transitional epithelial cell carcinoma of the bladder].
AB  - The prognosis of superficial bladder cancer in terms of local recurrence and
      transformation into invasive cancer is related to the multiplicity of tumor sites
      and the concomitant presence of "flat" tumours, such as dysplasia and carcinoma
      in situ. This study of 51 patients emphasizes the value of fluorescence
      cystoscopy in the early detection of superficial transitional cell carcinomas.
      This method is based on induction of fluorescence in carcinomatous sites which
      selectively accumulate an endogenous photosensitizer, protoporphyrin IX, in
      response to intravesical administration of its precursor, 5-aminolevulinic acid.
      The sensitivity of the method in the present series was close to 93%.
      Fluorescence cystoscopy is a simple and reliable method to map the bladder mucosa
      looking for areas of dysplasia and carcinoma in situ.

PMID- 9157822
TI  - [Ureteroscopic lithotripsy using the laser].
AB  - The Cagliari urology team is very satisfied with the use of the dye laser for
      ureteroscopic lithotripsy. This apparatus is recommended in units possessing a
      well equipped endourology room, otherwise it is simpler to use endoureteric
      ballistic lithotripsy, which also provides good results.

PMID- 9157823
TI  - [Diagnostic problems in prostatic pathology: microglandular lesions and
      intraductal epithelial proliferations].
AB  - In this review, the authors discuss the minimal criteria that allow for the
      distinction of prostatic adenocarcinoma with special emphasis on nuclear and
      nucleolar aspects and basal cell layer identification by routine and K 903
      immunoperoxidase technique. Differential diagnosis are reviewed including
      microglandular lesions (adenosis, sclerosing adenosis, atrophy) and
      intraglandular proliferations (basal cell hyperplasia, clear cell cribriform
      hyperplasia, intraductal dysplasia). The role of dysplasia as a premalignant
      lesion is also discussed.

PMID- 9157824
TI  - [Glomus tumors. Clinical, histological and immunohistochemical study. Apropos of
      29 cases].
AB  - This retrospective pathological study, based on twenty-nine glomus tumors, was
      conducted in order to define the histological or immunohistochemical diagnostic
      criteria in cases with atypical morphology. The immunohistochemical phenotype of
      glomus tumors was defined by means of identification of glomus cells, vessels and
      associated nerve fibres.

PMID- 9157825
TI  - Sources of discrepancies in the diagnosis of Hodgkin's disease by fine needle
      aspiration.
AB  - The aim of this study was to assess the value of Fine Needle Aspiration (FNA)
      Cytology in the diagnosis of Hodgkin's Disease (HD) and to identify the sources
      and nature of the inaccuracies related to this procedure. We retrospectively
      studied all cases cytologically diagnosed in our laboratory as HD during a five
      year period (1990-1994). We also traced cases in which FNA cytology failed to
      reveal HD and where a subsequent HD diagnosis was made by histology. Of the 99
      cases studied, a histological report was available for 93. In 82 cases FNA was
      carried out as part of the initial evaluation. In the remaining 17 cases the
      diagnosis of HD was known and FNA was performed in order to confirm or exclude a
      relapse. The results included 4 false positive for HD, 5 false negative and 3 HD
      suspicious cases (only one of which proved histologically to be HD while the
      remaining two were other neoplasms). The re-evaluation of the last 12 cases
      identified 3 different sources of error: a) Material adequacy criteria; b)
      Sampling techniques; c) Interpretation.

PMID- 9157826
TI  - [Adenomatoid tumors of the uterus. Study of 5 cases with immunohistochemical and
      ultrastructural confirmation of the mesothelial origin].
AB  - Five cases of adenomatoid tumors of the uterus (ATU) are reported. These benign
      lesions are discovered in 1% of the hysterectomy specimens, performed on 20- to
      85-years-old women. Their frequency is certainly underestimated, since ATU have
      the same macroscopic appearance as leiomyomas. Histologically, ATU are formed by
      gland-like and pseudovascular lumens, lined by regular, cuboidal or flattened
      cells, and surrounded by hyperplastic smooth muscle bundles. Immunohistochemical
      coexpression of cytokeratin and vimentin confirms with a mesothelial
      histogenesis. The ultrastructural study, showing luminal microvilli and
      desmosomes supports the hamartomatous development of ATU, corresponding to
      mesothelial inclusions from the peritoneum into the myometrium. Some giant or
      diffuse ATU, which are clinically disturbing, are differentiated from
      carcinomatous or vascular proliferations by frozen section examination. The
      treatment is made by surgical excision.

PMID- 9157827
TI  - Cystadenolymphoma of the parotid gland an immunohistochemical study of the
      epithelial component of twenty cases.
AB  - Carcinoembryonic antigen, epithelial membrane antigen, Keratin, Desmin, Vimentin,
      CD30, lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin, S-100 protein,
      somatostatin and glucagon were looked for using immunohistochemical methods in
      the epithelial component of 20 parotid gland cystadenolymphomas and 20 normal
      parotid glands. Carcino-embryonic antigen, ephithelial membrane antigen, S-100
      protein, and somatostatin were found in the epithelial cells of most of the
      cystadenolymphomas. In normal parotid tissue, carcinoembryonic antigen,
      epithelial membrane antigen, Keratin, alpha 1-antitrypsin, alpha 1
      antichymotrypsin, and S-100 protein were found in all three types of ductal
      cells, somatostatin only in intercalated and striated ductal cells, and lysozyme
      only in acinar and intercalated ductal cells. Desmin and CD30 were found in the
      epithelial component of seven of the 20 tumors versus none of the 20 normal
      parotid glands. Glucagon and Vimentin were negative both in tumor epithelial
      cells and in normal parotid ductal cells. Our results support the theory that
      cystadenolymphomas arise from epithelial cells. The presence of lysozyme in the
      epithelial tumor cells and in the intercalated ductal cells of normal parotid
      tissue suggest that cystadenolymphomas may arise from the intercalated ducts. The
      presence of S-100 and somatostatin may indicate that the tumor derives from
      neuroendocrine structures, but further studies are needed to clarify this point.

PMID- 9157828
TI  - [Doctor Anglas' observations on the presence of cytomegalic cells in macerated
      fetal tissues].
AB  - Early in this century, Anglas had observed in the renal tubules of a macerated
      fetus unusual giant structures, which turned out to be cytomegalic inclusion
      cells. But since he omitted to distinguish them by a suggestive term from
      previously known giant cells, his observation felt into oblivion. Yet, it
      constituted the first report on the occurrence of cytomegaly in France, and in
      general, the first indication of the histogenic origin of these cells, as well as
      of their resistance to autolysis.

PMID- 9157829
TI  - Malignant myoepithelioma of the breast. Case report with immunohistochemical
      study.
AB  - Malignant myoepitheliomas of the breast are rare. We report a case of spindle
      cell malignant myoepithelioma studied by light microscopy and
      immunohistochemistry. The malignant myoepithelial cells stained positively for
      cytokeratins, smooth muscle actin and vimentin, but not for epithelial membrane
      antigen. The tumor showed a focal positivity for S100 protein. A short review of
      the morphology and immunohistochemistry of cases reported in the international
      literature is given in a table. Morphologically malignant myoepitheliomas can be
      subdivided into spindle cell malignant myoepitheliomas and malignant
      adenomyoepitheliomas.

PMID- 9157830
TI  - Giant hemangioma in infant. A case presentation and literature review.
AB  - Giant hemangioma of infancy is a rare and extensive variant of the hemangiomas,
      that occurs in newborns and infants and is often complicated by life-threatening
      events. We describe herein an unusual case of a giant hemangioma in a female
      infant. At the age of 45 days she was admitted to the hospital because of
      increasing respiratory distress and distented abdomen. The response to supportive
      therapy was poor and the infant died from cardiac arrest on its 75th day of life.
      Autopsy revealed a giant tumor occupying extensive areas of the thoracic and
      abdominal cavity. The histologic diagnosis was compatible with a giant capillary
      hemangioma. A review of the literature was also attempted.

PMID- 9157831
TI  - [Errors in autopsy in Germany. Results of a multicenter study (I)].

PMID- 9157832
TI  - [Methods of suicide in an autopsy sample of the Institute of Forensic Medicine of
      the Hannover Medical School].
AB  - Between 1978 and 1987 513 cases of suicide were examined at the Institute of
      Legal Medicine of the Medical School of Hannover (337 males (65.7%) and 176
      females (34.3%). The greatest share of the suicides was found in the age group 18
      to 30. 42.1% of the cases showed positive alcohol concentrations with men
      accounting for a relatively higher share. The most frequently used methods for
      committing suicide were intoxications (28.1%), hanging (25.3%), firearms (17.2%),
      falling from great height (9.7%) and drowning (7.6%). The incidence in terms of
      sex showed marked differences in distribution, however. Women mostly used the
      following methods for committing suicide: Intoxication (37.4%), falling (17.6%)
      and hanging (17%). With men we found the following order: Hanging (29.7%),
      firearms (24.3%) and intoxications (23.1%). Compared with other institutes of
      legal medicine the five most frequent suicide methods showed similar
      distributions, but with a higher rate of intoxications. On the other hand there
      were distinct differences as to the relative frequency of the individual suicide
      methods in the total population and the respective number of autopsies performed.
      Especially in cases of gunshot wounds the number of autopsies performed to rule
      out homicide was higher. Of 2390 case of suicide registered in Greater Hannover
      an autopsy was ordered by the court in only 6.7%. According to our experience the
      autopsy rate seems too low, because homicide in the form of pretended suicide is
      not too rare.

PMID- 9157833
TI  - [Homicides without clues in children].
AB  - From 1990 to 1995, 274 deaths of infants (age range 7 days-6 years) were
      investigated in Munster, where there were no indications of suspicious
      circumstances. In 167 cases a legal autopsy was carried out and revealed 5
      homicides. In 107 cases where an autopsy was not ordered by the prosecutor 3
      homicides were discovered. A similar frequency of homicides in both groups
      indicates that the criteria used to form the basis of a decision by the
      prosecutor to release the body are insufficient. On average one out of 30 cases
      was found to be a homicide as the result of the autopsy where the initial
      assumption was death from natural causes.

PMID- 9157834
TI  - [An extended case of autoerotic accident].
AB  - A case of an autoerotic accident in an extended sense is reported. A heterosexual
      couple died from strangulation at the same time during common autoerotic
      practice.

PMID- 9157835
TI  - [Legal and actual problems in cadaver examination and autopsy (section 87 StPO)
      (I)].

PMID- 9157836
TI  - The birth and rearing of a textbook on pathology.

PMID- 9157837
TI  - Vascular hamartomas of the dorsal carpal region in three young thoroughbred
      horses.

PMID- 9157838
TI  - Rectal bleeding: a rare complication of abdominal pregnancy.
AB  - A rare case of abdominal pregnancy, causing massive rectal bleeding due to
      invasion of the rectal wall by the placenta, is reported.

PMID- 9157839
TI  - [Sonographic appearance of the canine kidney compared with pathologic-histologic
      morphology].
AB  - Aim of the present study was to evaluate the possibility whether the
      ultrasonographic appearance of the canine kidney can be attached to a specific
      histopathologic diagnosis. The sonographic examination was performed in 117 dogs
      that were presented in the Small Animal Clinic of Hannover Veterinary School,
      Germany, for euthanasia. After the euthanasia the kidneys were exenterated and
      evaluated pathohistologically in the Department of Pathology of Hannover
      Veterinary School. According to the sonographic changes the patients were
      classified into seven different groups and compared with the histopathologic
      findings. The results of this study demonstrate that it is currently not feasible
      to relate a gray-scale sonography image of a diffuse renal parenchymal alteration
      to a specific histopathologic diagnosis. It remains to be seen if it is possible
      to improve the renal ultrasonography with new diagnostic methods, e.g. color
      doppler ultrasonography.

PMID- 9157840
TI  - [A case of cutaneous epitheliotropic malignant lymphoma (mycosis fungoides) in a
      horse].
AB  - This article describes an eleven year old mare with apathy, fever, enlarged
      mandibular lymph nodes, skin lesions on the upper lip and edematous, grey-red
      mucous membranes in the nose, mouth and vulva. Histopathology revealed
      infiltrates with atypical lymphocytes forming Pautrier's microabscesses. The
      neoplastic cells had large, often indented nuclei. Immunohistology showed that
      some cells were CD3-positive (Pan T-cell-marker). The diagnosis of cutaneous
      epitheliotropic malignant lymphoma (Mycosis fungoides) was made. The etiology in
      the horse is unknown.

PMID- 9157841
TI  - [Investigations on the concentration and emission of ammonia and nitrous oxide in
      various deep litter keeping systems for fattening pigs and in slatted floor
      keeping].
AB  - Concentration of ammonia and nitrous oxide was measured in an air conditioned pig
      site with two chambers during six rounds (app. 650 measuring days) with different
      deep litter and a slatted floor keeping system for fattening pigs. Emissions and
      gaseous nitrogen losses were calculated. With exception of a system with mixing
      twice a week deep litter keeping leads to decrease of NH3 concentration (up to
      26%), partly also of NH3 emission, but to higher N2O emissions compared to liquid
      manure system. With exception of ENVIROZYME deep litter keeping all other deep
      litter systems cause higher gaseous nitrogen losses compared to slatted floor
      keeping.

PMID- 9157842
TI  - [Food hygiene aspects in the production of food fish in fishing].
AB  - The development of the aerob-mesophilic bacteria on epidermis and peritoneum of
      68 barbels was determined at 0, 4 and 8 hours after slaughtering. Therefore, one
      group of 34 animals was stored at 15.3 degrees C, an other equal one at 21.6
      degrees C. A change in germ counts per cm2 could be seen in none of the groups
      during the first 4 hours. However, unrefrigerated carcasses showed an increase of
      bacteria up to 5-fold between the 4th and 8th hour, whereas in the refrigerated
      group no change occurred during that time, too. Rinsing the fish after
      slaughtering resulted in a decrease of the initial bacterial counts by up to
      65.4% and so in significantly lower germ loads at the end of the storage time.
      These results were confirmed by contaminating 24 rainbow trout with Salmonella
      Infantis artificially. The frequency of detection did not change in refrigerated
      fish over 8 hours, while nearly doubling in unrefrigerated ones. Moreover, it
      could be shown that a Salmonella-concentration of only 30 CFU per 100 ml water
      was sufficient for contaminating fish in detectable grades. The study leads to
      the conclusion that the storage of instantly slaughtered fish in a common
      thermobox with freezing elements is suited for preserving its microbiological
      status for at least 8 hours. The caging of living fish after capture, which must
      be regarded critically under the aspect of treating animals in a humane way,
      seems therefore unnecessary.

PMID- 9157843
TI  - [Irreversible specific inhibition of E. coli inorganic pyrophosphatase with
      amines].
AB  - An unusually high reactivity of the carboxyl groups of the active site of E. coli
      inorganic pyrophosphatase towards amines was shown. Amino acid esters and other
      amines are specific irreversible inhibitors of the enzyme. The reaction involves
      the formation of an enzyme-inhibitor complex followed by the chemical
      modification of dicarboxylic amino acid residues. It is assumed that the binding
      of the positively charged inhibitor occurs at the binding site of cations
      activators.

PMID- 9157844
TI  - [Cloning of cDNA for RNA polymerase subunit from the fission yeast
      Schizosaccharomyces pombe by heterospecific complementation in Saccharomyces
      cerevisiae].
AB  - The rpb10 cDNA of the fission yeast Schizosaccharomyces pombe, encoding one of
      the five small subunits common to all three nuclear DNA-dependent RNA
      polymerases, was isolated from an expression cDNA library by two independent
      approaches: PCR-based screening and direct suppression by means of heterospecific
      complementation of a temperature-sensitive mutant defective in the corresponding
      gene of Saccharomyces cerevisiae. The cloned Sz. pombe cDNA encodes a protein
      Rpb10 of 71 amino acids with an M of 8,275 Da, sharing 51 amino acids (71%
      identity) with the subunit ABC10 beta of RNA polymerases I-III from S.
      cerevisiae. All eukaryotic members of this protein family have the same general
      organization featuring two highly conserved motifs (RCFT/SCGK and RYCCRRM) around
      an atypical zinc finger and an additional invariant HVDLIEK motif toward the C
      terminal end. The last motif is only characteristics for homologs from
      eukaryotes. In keeping with this remarkable structural conservation, the Sz.
      pombe cDNA also fully complemented a S. cerevisiae deletion mutant lacking
      subunit ABC10 beta (null allele rpb10-delta 1::HIS3).

PMID- 9157845
TI  - [Bacterial synthesis of immunogenic epitopes of foot-and-mouth disease virus
      fused either to human necrosis factor or to hepatitis B core antigen].
AB  - Using recombinant DNA technology, construction and bacterial expression of genes
      was carried out which code for hybrid proteins, human tumor necrosis factor and
      hepatitis B core protein fused to immunogenic epitopes of foot-and-mouth disease
      virus, strains A22 and O1-194. Hybrids of tumor necrosis factor with foot-and
      mouth disease antigenic determinants protected laboratory animals against the
      experimental challenge with a homologous strain of foot-and-mouth disease virus.
      Hybrid protein that contained immunogenic regions of two strains, A22 and O1-194,
      protected animals against infection with both A and O serotypes. Hybrid proteins
      based on hepatitis B virus core antigen retained the ability to assemble into
      core-like particles.

PMID- 9157846
TI  - [Cyclic oligonucleotides. II. Regularities in the formation of polycyclic
      structures].
AB  - Cyclization of a 38-mer oligodeoxyribonucleotide on a cyclic template was studied
      by the chemical and enzymic ligation methods. Both structures and yields of the
      reaction products depended on the ligation method and the nucleotide and template
      sequences. The chemical ligations resulted in the formation of catenanes, whose
      structures were confirmed by hydrolysis with the MvaI restriction endonuclease.
      Presence of G/C-rich clusters near the formed internucleotide bond favored the
      catenane formation.

PMID- 9157847
TI  - [Scientific information support for research in physico-chemical biology
      (analytical review)].

PMID- 9157848
TI  - [Is there a hope in fight against AIDS?].

PMID- 9157849
TI  - [Nucleotide sequence of cDNA and organization of the gene for alpha-subunit of
      photoreceptor phosphodiesterase of cyclic GMP in human retinal cones].
AB  - Five clones were isolated from a human retina cDNA library whose cDNA inserts
      allowed reconstruction of the total sequence of the human clone cGMP
      phosphodiesterase alpha'-subunit cDNA comprising 3455 bp. The protein's deduced
      sequence contains 858 amino acids residues with molecular mass 99,169 Da. A
      substantial homology was revealed between the amino acid sequence of the human
      cones cGMP-phosphodiesterase alpha'-subunit and the corresponding sequences of
      alpha, beta, and alpha' subunits of visual cGMP-phosphodiesterase of bovine,
      murine, chicken and human retinas. Four recombinant bacteriophages were isolated
      from a genomic library whose inserts made it possible to reconstruct a 32-kb
      fragment of the human cones cGMP-phosphodiesterase alpha'-subunit gene. 5'
      Flanking region of the gene and first 14 exons, encoding an N-terminal segment of
      the protein, along with the adjacent intron segments were sequenced.

PMID- 9157850
TI  - [Proteolysis of human proinsulin catalysed by native, modified, and immobilized
      trypsin].
AB  - Proteolysis of recombinant human proinsulin by the native trypsin, by trypsin
      modified with a copolymer of vinylpyrrolidone and acrolein, and by the same
      modified trypsin immobilized on Silochrom 1.5 was studied by RP HPLC and mass
      spectrometry. Rate constants of the main stages of proinsulin hydrolysis by the
      native trypsin were estimated. The values of rate constants of the digestions of
      the most easily hydrolyzable bonds (those formed by the pairs of the basic amino
      acid residues) in proinsulin were found to be of the same order as those formed
      by the separate lysine residues (Lys7) and those formed by the four basic amino
      acid residues of the C-terminal cluster of melittin. It was established that
      covalent trypsin binding to the copolymer did not change the ratio of the rate
      constants of the individual stages of proinsulin hydrolysis, whereas after the
      immobilization of modified trypsin on the Silochrome, the formation of diarginyl
      insulin-ArgArg, intermediate forms of hydrolyzed insulin, and desThr-insulin
      proceeds with comparable rates.

PMID- 9157851
TI  - [Recombinant human insulin. VII. Increased efficacy of chromatographic separation
      based on a principle of bifunctionality].
AB  - Retention mechanisms of insulin and deamido[AsnA21] insulin on the bifunctional
      sorbent Armsphere-C8(PR) in conditions of reversed-phase chromatography (HPLC and
      ion-pair HPLC) were studied. In accordance with the chemical differences of these
      proteins, molecular mechanisms of their interaction with silica gel modified with
      hydrophobic and ion-exchange groups were revealed. The possibility of
      simultaneous interaction of sorbed proteins with the stationary phase by both
      mechanisms under conditions of reversed-phase HPLC was demonstrated. The
      dependences of the separation selectivity and resolution on the mobile phase
      composition and properties (a salt buffer type, pH, ionic strength) were found.
      It was demonstrated that the separation selectivity can be regulated by altering
      the contribution of each of the two separation mechanisms and the bifunctional
      sorbent used allows higher selectivity in the separation of close protein analogs
      than monofunctional sorbents.

PMID- 9157852
TI  - Spiral CT angiography of the abdomen and pelvis: interventional applications.
AB  - Spiral CT angiography may be a useful adjunct for interventional radiologists in
      imaging vessels within the abdomen and pelvis. Specifically, the potential to
      assess abdominal aortic aneurysms preoperatively is within the realm of spiral CT
      angiography so long as scanners can quickly change collimation and table feed
      during the examination. The technique is also useful for imaging metal and
      nonmetal vascular grafts. The splanchnic arteries may be imaged in instances in
      which proximal vascular patency and course is questioned. The portal vein and its
      branches may be imaged prospectively with spiral CT angiography or
      retrospectively by postprocessing routine abdominal CT image data. The normal
      renal vasculature including accessory vessels may be imaged as part of
      preoperative evaluation for renal transplantation or for repair of ureteropelvic
      junction obstruction. Renal artery aneurysms may also be followed with spiral CT
      angiograms. Hemodynamically significant renal arterial stenoses may be detected
      with spiral CT angiography; grading the severity of those stenoses is within the
      realm of spiral CTA so long as careful attention is paid to technique.

PMID- 9157853
TI  - Liposarcoma of the stomach.
AB  - We present a case of gastric liposarcoma, a very uncommon pathology; only nine
      cases have been reported in the literature. We describe the radiologic findings
      of this neoplasm and emphasize the correlation between computed tomography (CT)
      and the macroscopic morphology of the tumor, which is conditioned by its
      histology. In our case, CT demonstration of fatty areas within the gastric mass
      facilitated the diagnosis. This finding has not been described for liposarcomas
      of the stomach.

PMID- 9157854
TI  - Crescent-shaped necrosis: a new imaging sign suggestive of stromal tumor of the
      small bowel.
AB  - We report three cases of unsuspected stromal tumors of the small bowel (STSB).
      These cases were diagnosed preoperatively by sonography, the imaging was
      completed for some with barium studies, computed tomography, magnetic resonance
      imaging, or angiography. To our knowledge, the use of this noninvasive technique
      for detecting this type of tumor has not been described in the literature.
      Moreover, we believe that some sonographic findings such as crescentic tumoral
      necrosis may appear highly suggestive of STSB.

PMID- 9157855
TI  - The value of hyoscine butylbromide in abdominal MR imaging with and without oral
      magnetic particles.
AB  - PURPOSE: The purpose of this article was to assess the impact of intravenous (IV)
      anticholinergic hyoscine butylbromide in abdominal magnetic resonance (MR)
      imaging with oral magnetic particles (OMP) [ABDOS-CAN, Ferristene (USAN), Nycomed
      Imaging AS, Oslo, Norway]. MATERIALS AND METHODS: In 31 patients with abdominal
      tumors, T1-weighted spin-echo (SE) images (SE 600/ 15; 1.5 T) were obtained
      without and with IV hyoscine butylbromide (20 mg) before and after administration
      of 800 ml of OMP. Two blinded readers assessed motion artifacts, bowel-wall
      visualization, and lesion delineation on the four sets of T1-weighted images. The
      two-tailed Wilcoxon paired sample test was used for statistical analysis (p <
      .05). RESULTS: Hyoscine butylbromide reduced motion artifacts and improved bowel
      wall visualization on precontrast and OMP-enhanced images at a statistically
      significant level (p = 0.0006-0.037). The lowest degree of artifacts was recorded
      on OMP images with hyoscine butylbromide. OMP with hyoscine butylbromide
      significantly improved lesion delineation compared to studies without
      antiperistaltic drug before (p = 0.019) and after OMP administration (p = 0.01).
      CONCLUSIONS: The authors conclude that the use of IV hyoscine butylbromide is
      recommended for OMP-enhanced abdominal MR imaging with T1-weighted SE pulse
      sequences at 1.5 T.

PMID- 9157856
TI  - Acute colonic obstruction caused by intussusception and extrusion of a sigmoid
      lipoma through the anus after barium enema.
AB  - Colonic lipomas are often asymptomatic, but large lipomas may produce abdominal
      pain, diarrhea, constipation, hemorrhage, and intussusception. We report a young
      woman with a colonic lipoma who presented as an acute abdominal emergency with
      total colonic obstruction and severe pain associated with intussusception and
      extrusion of the tumor through the anus. The case was interesting because of its
      presentation after a double-contrast barium enema and because of the patient's
      young age and the tumor's location on the left side of the colon.

PMID- 9157857
TI  - Colocolic intussusception caused by pneumatosis cystoides coli.
AB  - We report the case of a 29-year-old man with a long-standing history of abdominal
      pain related to an intermittent colocolic intussusception caused by pneumatosis
      cystoides coli. To our knowledge, only one similar case has been reported in the
      English-language literature.

PMID- 9157858
TI  - Pneumatosis cystoides intestinalis with pneumoperitoneum and
      pneumoretroperitoneum following chemotherapy.
AB  - Pneumatosis cystoides intestinalis (PCI) is a relatively rare, mostly benign,
      condition. We report a case of chemotherapy-induced PCI with free retro- and
      intraperitoneal gas in a 17-year-old man with acute lymphoblastic leukemia. Chest
      radiography and upright abdominal radiography showed free intra- and
      retroperitoneal gas; computed tomography demonstrated subserosal gas collections.
      Conservative treatment with oxygen, metronidazol, and parenteral alimentation was
      performed, and PCI resolved within 2 weeks.

PMID- 9157859
TI  - Pseudotumorous enlargement of the paracaval portion of the caudate lobe: a report
      of two cases with CT and MR appearance.
AB  - The computed tomographic (CT) and magnetic resonance appearance of pseudotumorous
      enlargement of the paracaval portion (PCP) of the caudate lobe of the liver are
      presented in two cirrhotic patients. The enlarged PCP was hyperattenuated on
      precontrast CT and hyperintense on T1-weighted images. The middle and right
      hepatic veins were displaced around the PCP. The presence of a portal vein branch
      penetrating the center of the enlarged PCP was important to distinguish it from
      other hepatic masses in the two patients.

PMID- 9157860
TI  - Intraoperative US diagnosis of pylephlebitis (portal vein thrombosis) as a
      complication of appendicitis: a case report.
AB  - We report a case of infectious thrombosis of the superior mesenteric vein
      (pylephlebitis) that was suspected preoperatively with computed tomography and
      confirmed at intraoperative ultrasonography as confined to the extrahepatic
      portal vein and superior mesenteric vein. Intraoperative ultrasonography revealed
      intraluminal echogenic thrombus material in the dilated superior mesenteric and
      extrahepatic portal veins, slightly dilated open splenic vein, and numerous
      venous collaterals in the hepatoduodenal ligament. When preoperative imaging
      studies are inconclusive, intraoperative sonography can confirm the correct
      diagnosis of pylephlebitis and may give valuable information about the extent of
      the thrombosis.

PMID- 9157861
TI  - Methodological assessment of combined spiral CT angiography and CT arterial
      portography.
AB  - BACKGROUND: To assess an optimal methodology of combined spiral computed
      tomographic (CT) angiography (CTA) and CT arterial portography (CTAP) for
      detection and characterization of liver tumors. METHODS: We performed spiral CTAP
      only in five patients with 30-32% contrast (subset A), CTAP combined with
      preceding spiral CTA using 30-32% contrast in 19 (subset B), and CTAP combined
      with preceding spiral CTA with 60-64% contrast in seven (subset C). The CT
      numbers of the aorta immediately before preceding CTA and subsequent CTAP and the
      CT numbers of malignant tumor and liver parenchyma with CTAP were measured.
      RESULTS: The differences of the CT number between the malignant tumor and liver
      parenchyma on CTAP were 61.1-161.8 (mean +/- SD, 114.5 +/- 39.3) HU, 50.7-164.8
      (104.2 +/- 31.2) HU, and 101.2-368.3 (219.5 +/- 90.5) HU in subsets A, B, and C,
      respectively. Two cavernous hemangiomas showed pathognomonic findings with
      preceding CTA. CONCLUSION: Combination of preceding spiral CTA and subsequent
      spiral CTAP using 30% contrast with a 5-min interval is an optimal method for
      detection and characterization of liver tumors.

PMID- 9157862
TI  - Hyperintense benign liver lesions on spin-echo T1-weighted MR images: pathologic
      correlations.
AB  - BACKGROUND: To determine the incidence of hyperintensity on T1-weighted spin echo
      (SE) images in benign liver lesions, value of fat-suppressed magnetic resonance
      (MR) imaging for the detection of fat within these lesions, and the causes of
      hyperintensity by correlation to pathologic examinations. METHODS: Five hundred
      forty-nine patients with 805 benign liver lesions including 585 hemangiomas, 188
      focal nodular hyperplasias (FNHs), 14 hepatic adenomas (HAs), 14 focal fatty
      infiltrations (FFIs), two biliary cystadenomas, and two hemorrhagic cysts were
      examined by T2-weighted and T1-weighted SE MR imaging. For hyperintense lesions
      on T1-weighted SE images, fat-suppressed images were obtained by selective
      presaturation of fat. RESULTS: Thirty-two lesions (four FNHs, 10 HAs, 14 FFIs,
      two biliary cystadenomas, and two hemorrhagic cysts) appeared hyperintense on T1
      weighted SE images; 21 of these became hypointense on the fat-suppressed T1
      weighted SE images (one FNH, six HAs, and 14 FFIs) and contained fat at
      pathological examination. The other 11 lesions remained hyperintense on fat
      suppressed T1-weighted SE images and had no fat deposition. Causes of
      hyperintensity in these cases were sinusoidal dilatation, copper deposition,
      hemorrhage, and high protein content. CONCLUSION: Among benign liver lesions,
      hyperintensity on T1-weighted SE images is rare (3.9%). Causes of this
      hyperintensity are fat deposition, copper accumulation, sinusoidal dilatation,
      bemorrhage, and high protein content. Fat-suppressed imaging can distinguish fat
      deposition from other causes of hyperintensity.

PMID- 9157863
TI  - Cat scratch disease as a rare cause of obstructive jaundice: a case report.

PMID- 9157864
TI  - Retrograde cholangiography of malignant biliary strictures: spectrum of
      appearances and pitfalls.
AB  - PURPOSE: To evaluate retrograde cholangiograms, explore the morphology of
      malignant biliary strictures, and determine if there are any features that may
      indicate a specific diagnosis. MATERIALS AND METHODS: The retrograde
      cholangiograms of 514 patients were reviewed. Cases with clinical follow-up and
      subsequent studies indicating malignant involvement of the biliary tree were
      identified. Fifty patients were found. RESULTS: Carcinoma of the pancreatic head
      was the most common disease with 21 patients in this group. The morphology of the
      bile duct at the point of involvement was nonspecific comprising shouldered
      intrinsic appearing lesions as well as tapered in other cases. Pancreatic duct
      dilatation was a relatively specific finding occurring in 80% of this group.
      Other malignancies to involve the bile ducts included cholangiocarcinoma,
      metastases, ampullary carcinoma and gallbladder carcinoma. As with pancreatic
      carcinoma, the morphology of the lesion (e.g., shouldered versus tapered, length
      of stricture, severity of proximal dilatation) did not aid in the specific
      diagnosis of the pathology. Illustrative cases are presented where the morphology
      was unexpected for the eventual diagnosis (e.g., simulating intraluminal filling
      defects). CONCLUSION: The cholangiographic appearance of a biliary stricture is
      usually not helpful in the specific diagnosis of the underlying etiology.
      Carcinoma of the pancreatic head may be suspected if pancreatic duct dilatation
      is also found. This article presents some unusual cholangiographic pitfalls that
      were identified, which initially distracted from the ultimate diagnosis.

PMID- 9157865
TI  - The retropancreatic colon: a congenital anomaly.
AB  - We report the first case of a retropancreatic colon. This condition appears to be
      a congenital internal intra-abdominal hernia secondary to abnormal intestinal
      rotation in the embryo.

PMID- 9157866
TI  - Comparison of helical CT and MR imaging in detecting and staging small pancreatic
      adenocarcinoma.
AB  - BACKGROUND: To compare the value of helical computed tomography (CT) and various
      pulse sequences of magnetic resonance (MR) imaging in the detection and staging
      of small pancreatic adenocarcinoma. METHODS: Small pancreatic adenocarcinomas (<
      or = 2 cm in diameter) in eight patients were evaluated with both helical CT and
      MR imaging. Five MR imaging pulse sequences that included fat-suppressed T1
      weighted images and dynamic study using fast multiplanar spoiled gradient
      recalled technique were compared for the tumor detectability. To evaluate the
      tumor vascularity, angiographic findings were also investigated. RESULTS: Helical
      CT delineated the tumor in five cases, and MR imaging depicted the tumor in seven
      cases. MR imaging could detect the tumor of 0.8 cm in diameter clearly. Although
      helical CT and dynamic MR imaging missed the tumor of 2 cm with relative
      hypervascularity, fat-suppressed T1-weighted MR imaging demonstrated it
      precisely. As for the tumor staging, MR imaging was equal or slightly superior to
      helical CT. CONCLUSION: MR imaging is the first modality of choice to evaluate
      small pancreatic adenocarcinoma, and fat-suppressed T1-weighted images and
      dynamic study must be performed.

PMID- 9157867
TI  - Diagnosis of portal venous invasion by pancreatobiliary carcinoma: value of
      endoscopic ultrasonography.
AB  - BACKGROUND: We evaluated the usefulness of endoscopic ultrasonography for
      detecting pancreatobiliary carcinoma and assessing portal venous invasion by
      carcinoma. METHODS: Seventy-three patients with pancreatic carcinoma (54
      patients) or bile duct carcinoma (19 patients) underwent endoscopic
      ultrasonography, transabdominal ultrasonography, computed tomography (CT), and
      angiography. All patients underwent tumor resection and histological examination
      for portal venous invasion. Results of endoscopic ultrasonography were compared
      with those of other imaging modalities. RESULTS: Histopathology revealed portal
      venous invasion in 20 patients. Endoscopic ultrasonography was significantly more
      sensitive (96%) than ultrasonography (81%), CT (86%), and angiography (59%) in
      detecting carcinomas. On endoscopic ultrasonography, loss of the echogenic vessel
      parenchymal sonographic interface or a tumor within the vessel lumen indicated
      portal venous invasion. For diagnosing portal venous invasion, endoscopic
      ultrasonography was more sensitive (95%) and accurate (93%) than ultrasonography
      (55% and 67%), CT (65% and 74%), and angiography (75% and 79%), respectively.
      CONCLUSION: Endoscopic ultrasonography is the most accurate tool for detecting
      pancreatobiliary carcinomas and assessing portal venous invasion.

PMID- 9157868
TI  - Mesoblastic nephroma in an adult: spiral CT appearance.

PMID- 9157869
TI  - MR imaging of primary uterine lymphoma.
AB  - Primary malignant lymphoma of the uterus is a rare disease. We present the MR
      findings in three cases where the uterus was the initial site. MR findings wer
      retrospectively evaluated. Although the intact junctional zone is a specific
      finding for lymphoma, diffuse enlargement of the uterus and relatively
      homogeneous signal intensity on MR imaging in spite of large tumor size are
      helpful for diagnosing uterine lymphoma.

PMID- 9157871
TI  - Primary isolated urethral amyloidosis.
AB  - We report an unusual case of primary amyloidosis isolated to the urethra in a
      patient with tender, periurethral masses and obstructive voiding symptoms. When
      not secondary to other phenomena, amyloidosis most commonly affects the skin,
      respiratory, and urinary tracts. Isolated amyloidosis of the urethra should be in
      the differential diagnosis of a patient with irregular strictures of the penile
      urethra, a clinical presentation consistent with urethral carcinoma, and no
      evidence of systemic disease.

PMID- 9157870
TI  - Genital tract tuberculosis with peritoneal involvement: MR appearance.
AB  - The MR appearance of a case of genital tract tuberculosis is reported. The
      finding of a large amount of loculated fluid containing septations and debris on
      ultrasound along with bilateral hydropic fallopian tubes and a thickened omentum
      on MRI permitted the diagnosis to be suggested preoperatively. With increasing
      prevalence, such unusual manifestations of tuberculosis will be seen more
      frequently.

PMID- 9157872
TI  - Pencil-thin stools and constipation: indications for barium enema?

PMID- 9157875
TI  - Direct measurement of angles between bond vectors in high-resolution NMR.
AB  - Angles between two interatomic vectors are measured for structure elucidation in
      solution nuclear magnetic resonance (NMR). The angles can be determined directly
      by using the effects of dipole-dipole cross-correlated relaxation of double
      quantum and zero-quantum coherences. The measured rates can be directly related
      to the angular geometry without need for calibration of a Karplus-type curve, as
      is the case for scalar coupling measurements, and depend only on the rotational
      correlation time of the molecule as an empirical parameter. This makes the
      determination of torsional angles independent from the measurement of coupling
      constants. The two interatomic vectors can in principle be arbitrarily far apart.
      The method was demonstrated on the measurement of the peptide backbone angle psi
      in the protein rhodniin, which is difficult to determine in solution by NMR
      spectroscopy.

PMID- 9157877
TI  - Europa's differentiated internal structure: inferences from two Galileo
      encounters.
AB  - Doppler data generated with the Galileo spacecraft's radio carrier wave during
      two Europa encounters on 19 December 1996 (E4) and 20 February 1997 (E6) were
      used to measure Europa's external gravitational field. The measurements indicate
      that Europa has a predominantly water ice-liquid outer shell about 100 to 200
      kilometers thick and a deep interior with a density in excess of about 4000
      kilograms per cubic meter. The deep interior could be a mixture of metal and rock
      or it could consist of a metal core with a radius about 40 percent of Europa's
      radius surrounded by a rock mantle with a density of 3000 to 3500 kilograms per
      cubic meter. The metallic core is favored if Europa has a magnetic field.

PMID- 9157876
TI  - Large molecular third-order optical nonlinearities in polarized carotenoids.
AB  - Garito and co-workers have suggested a mechanism to dramatically increase the
      second hyperpolarizability, gamma, in linear pi-electron-conjugated molecules.
      Polarization is introduced that leads to a difference between the dipole moments
      of the molecule's ground state and excited state. Here a series of carotenoids
      was examined that had increasing intramolecular charge transfer (ICT) from the
      polyenic chain to the acceptor moiety in the ground state, and gamma was measured
      for these compounds as a function of wavelength by third-harmonic generation. The
      compound with the greatest ICT exhibited a 35-fold enhancement of gammamax (the
      gamma measured at the peak of the three-photon resonance) relative to the
      symmetric molecule beta-carotene, which itself has one of the largest third-order
      nonlinearities known. Stark spectroscopic measurements revealed the existence of
      a large difference dipole moment, Delta mu, between the ground and excited state.
      Quantum-chemical calculations underline the importance of interactions involving
      states with large Delta mu.

PMID- 9157878
TI  - Europa's magnetic signature: report from Galileo's pass on 19 December 1996.
AB  - On 19 December 1996 as Galileo passed close to Jupiter's moon, Europa, the
      magnetometer measured substantial departures from the slowly varying background
      field of Jupiter's magnetosphere. Currents coupling Europa to Jupiter's
      magnetospheric plasma could produce perturbations of the observed size. However,
      the trend of the field perturbations is here modeled as the signature of a Europa
      centered dipole moment whose maximum surface magnitude is approximately 240
      nanotesla, giving a rough upper limit to the internal field. The dipole
      orientation is oblique to Europa's spin axis. This orientation may not be
      probable for a field generated by a core dynamo, but higher order multipoles may
      be important as they are at Uranus and Neptune. Although the data can be modeled
      as contributions of an internal field of Europa, they do not confirm its
      existence. The dipole orientation is also oblique to the imposed field of Jupiter
      and thus not directly produced as a response to that field. Close to Europa,
      plasma currents appear to produce perturbations with scale sizes that are small
      compared with a Europa radius.

PMID- 9157882
TI  - Discrete determinants in transfer RNA for editing and aminoacylation.
AB  - During translation errors of aminoacylation are corrected in editing reactions
      which ensure that an amino acid is stably attached to its corresponding transfer
      RNA (tRNA). Previous studies have not shown whether the tRNA nucleotides needed
      for effecting translational editing are the same as or distinct from those
      required for aminoacylation, but several considerations have suggested that they
      are the same. Here, designed tRNAs that are highly active for aminoacylation but
      are not active in translational editing are presented. The editing reaction can
      be controlled by manipulation of nucleotides at the corner of the L-shaped tRNA.
      In contrast, these manipulations do not affect aminoacylation. These results
      demonstrate the segregation of nucleotide determinants for the editing and
      aminoacylation functions of tRNA.

PMID- 9157883
TI  - Ndj1p, a meiotic telomere protein required for normal chromosome synapsis and
      segregation in yeast.
AB  - The Saccharomyces cerevisiae gene NDJ1 (nondisjunction) encodes a protein that
      accumulates at telomeres during meiotic prophase. Deletion of NDJ1 (ndj1Delta)
      caused nondisjunction, impaired distributive segregation of linear chromosomes,
      and disordered the distribution of telomeric Rap1p, but it did not affect
      distributive segregation of circular plasmids. Induction of meiotic recombination
      and the extent of crossing-over were largely normal in ndj1Delta cells, but
      formation of axial elements and synapsis were delayed. Thus, Ndj1p may stabilize
      homologous DNA interactions at telomeres, and possibly at other sites, and it is
      required for a telomere activity in distributive segregation.

PMID- 9157884
TI  - t-SNARE activation through transient interaction with a rab-like guanosine
      triphosphatase.
AB  - Intracellular vesicle targeting involves the interaction of vesicle proteins,
      termed v-SNAREs, with target membrane proteins, termed t-SNAREs. Assembly of v
      SNARE-t-SNARE targeting complexes is modulated by members of the Sec1-Sly1
      protein family, and by small guanosine triphosphatases termed Rabs. The
      interactions of these proteins during assembly of the endoplasmic reticulum-to
      Golgi targeting complex in Saccharomyces cerevisiae were studied. The data
      suggest that the Rab protein Ypt1p transiently interacts with the t-SNARE Sed5p
      and results in displacement of the negative regulator Sly1p, allowing subsequent
      formation of the v-SNARE-t-SNARE targeting complex.

PMID- 9157885
TI  - Promoter recognition as measured by binding of polymerase to nontemplate strand
      oligonucleotide.
AB  - In transcription initiation, the DNA strands must be separated to expose the
      template to RNA polymerase. As the closed initiation complex is converted to an
      open one, specific protein-DNA interactions involving bases of the nontemplate
      strand form and stabilize the promoter complex in the region of unwinding.
      Specific interaction between RNA polymerase and the promoter in Escherichia coli
      was detected and quantified as the binding affinity of nontemplate
      oligonucleotide sequences. The RNA polymerase subunit sigma factor 70 contacted
      the bases of the nontemplate DNA strand through its conserved region 2; a
      mutation that affected promoter function altered the binding affinity of the
      oligonucleotide to the enzyme.

PMID- 9157886
TI  - Ligand-specific opening of a gated-porin channel in the outer membrane of living
      bacteria.
AB  - Ligand-gated membrane channels selectively facilitate the entry of iron into
      prokaryotic cells. The essential role of iron in metabolism makes its acquisition
      a determinant of bacterial pathogenesis and a target for therapeutic strategies.
      In Gram-negative bacteria, TonB-dependent outer membrane proteins form energized,
      gated pores that bind iron chelates (siderophores) and internalize them. The time
      resolved operation of the Escherichia coli ferric enterobactin receptor FepA was
      observed in vivo with electron spin resonance spectroscopy by monitoring the
      mobility of covalently bound nitroxide spin labels. A ligand-binding surface loop
      of FepA, which normally closes its transmembrane channel, exhibited energy
      dependent structural changes during iron and toxin (colicin) transport. These
      changes were not merely associated with ligand binding, but occurred during
      ligand uptake through the outer membrane bilayer. The results demonstrate by a
      physical method that gated-porin channels open and close during membrane
      transport in vivo.

PMID- 9157888
TI  - Gene expression profiles in normal and cancer cells.
AB  - As a step toward understanding the complex differences between normal and cancer
      cells in humans, gene expression patterns were examined in gastrointestinal
      tumors. More than 300,000 transcripts derived from at least 45,000 different
      genes were analyzed. Although extensive similarity was noted between the
      expression profiles, more than 500 transcripts that were expressed at
      significantly different levels in normal and neoplastic cells were identified.
      These data provide insight into the extent of expression differences underlying
      malignancy and reveal genes that may prove useful as diagnostic or prognostic
      markers.

PMID- 9157887
TI  - Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness.
AB  - Both subjective and electroencephalographic arousal diminish as a function of the
      duration of prior wakefulness. Data reported here suggest that the major criteria
      for a neural sleep factor mediating the somnogenic effects of prolonged
      wakefulness are satisfied by adenosine, a neuromodulator whose extracellular
      concentration increases with brain metabolism and which, in vitro, inhibits basal
      forebrain cholinergic neurons. In vivo microdialysis measurements in freely
      behaving cats showed that adenosine extracellular concentrations in the basal
      forebrain cholinergic region increased during spontaneous wakefulness as
      contrasted with slow wave sleep; exhibited progressive increases during
      sustained, prolonged wakefulness; and declined slowly during recovery sleep.
      Furthermore, the sleep-wakefulness profile occurring after prolonged wakefulness
      was mimicked by increased extracellular adenosine induced by microdialysis
      perfusion of an adenosine transport inhibitor in the cholinergic basal forebrain
      but not by perfusion in a control noncholinergic region.

PMID- 9157889
TI  - Brain regions responsive to novelty in the absence of awareness.
AB  - Brain regions responsive to novelty, without awareness, were mapped in humans by
      positron emission tomography. Participants performed a simple reaction-time task
      in which all stimuli were equally likely but, unknown to them, followed a complex
      sequence. Measures of behavioral performance indicated that participants learned
      the sequences even though they were unaware of the existence of any order. Once
      the participants were trained, a subtle and unperceived change in the nature of
      the sequence resulted in increased blood flow in a network comprising the left
      premotor area, left anterior cingulate, and right ventral striatum. Blood flow
      decreases were observed in the right dorsolateral prefrontal and parietal areas.
      The time course of these changes suggests that the ventral striatum is responsive
      to novel information, and the right prefrontal area is associated with the
      maintenance of contextual information, and both processes can occur without
      awareness.

PMID- 9157890
TI  - Directory of oncology nurse researchers.

PMID- 9157891
TI  - Downsizing is a dud.

PMID- 9157892
TI  - Second annual Helene Hudson Memorial Lecture. I am a nurse.
AB  - The focus of this study was an exploration of the nature of exceptionally
      competent oncology nursing practice. Through a combination of data gathering
      approaches--conversation, observation and narrative exchange--the beliefs,
      actions and effects of the actions of eight exemplary nurse informants were
      studied. Analysis revealed three themes related to the action of the exemplary
      nurses: Dialogue in silence, mutual touch and sharing the lighter side of life.
      Additional analysis led to a category called effects of nursing actions. Again,
      three themes were highlighted as effects: Affirmation of the nurse and patient,
      connecting and joint transcendence.

PMID- 9157893
TI  - [The learning needs of the cancer patient: a conceptual analysis].
AB  - This paper offers a conceptual analysis of the term "learning need" of a cancer
      population. This analysis was made according to the steps recommended by Wilson
      (1969). In order to properly understand the essential features of the learning
      need concept, it is defined by focusing on its characteristics: cognitive
      knowledge, affective knowledge, psychomotor knowledge and the notion of learning.
      For the sake of clarity, the expression "learning need" was analyzed by examining
      a group of closely related concepts: information need, desire to learn and search
      for information. Although it is often used, the boundary between these concepts
      is not clearly identified. Some of these concepts may even be confused for each
      other. The paper concludes by explaining the nature of the cancer patient's
      learning needs.

PMID- 9157894
TI  - The research utilization process: the use of guided imagery to reduce anxiety.
AB  - In the rapidly changing health care environment, nurses need to keep current with
      developments, assess their applicability to practice, and make changes where
      appropriate. There is evidence that nursing research is underutilized and that a
      considerable gap exists between nursing research and practice (Bostrum & Suter,
      1993; Brett, 1987; Sokop & Coyle, 1990). The objectives of a study carried out on
      a bone marrow transplant unit in a teaching hospital were to: (1) by introducing
      a framework for research-based care, enhance research utilization in a selected
      setting, and (2) evaluate the outcomes of research utilization on a specific
      clinical nursing problem chosen by nurses and researchers. This paper describes
      the research utilization process and its outcomes, presents an evaluation of the
      participatory approach from the perspective of the participating nurses, and
      discusses facilitators and barriers to research utilization. Guided imagery was
      the intervention used to decrease patient anxiety.

PMID- 9157895
TI  - Baccalaureate education in oncology nursing: the dream is becoming a reality for
      Ontario nurses.

PMID- 9157896
TI  - Community oncology clinic liaison nurse.

PMID- 9157897
TI  - Detecting abuse against women in the home.
AB  - Assault is the single major cause of injury to women. Between 1.8 and 4.0 million
      American women are abused in their homes each year. The perpetrator of domestic
      violence is usually male (95%), the victim usually female. Most domestic violence
      is a result of the learning and reinforcement of a power imbalance between
      partners. Home care providers are in a prime position to detect actual or
      potential abuse against women, but the dynamics of abuse often produce an
      artificial home atmosphere, with the occupants ill at ease with the home care
      provider. This makes detection more difficult. Although a direct inquiry about
      abuse is usually the best approach, both distinct and subtle signs of abuse can
      be detected by informed providers. Once physical abuse is detected, it is of
      paramount importance to select the most appropriate referrals, resources, and
      strategies to assist the woman in freeing herself of abuse. Emergency departments
      are recommended for immediate physical treatment, shelters for therapeutic and
      rehabilitative services.

PMID- 9157898
TI  - At home with diversity.
AB  - This article describes the ways in which knowledge and understanding of culture
      can help the health care provider better plan for in-home care of patients from
      diverse cultural and ethnic backgrounds. A presentation of basic value and belief
      systems is followed by examples of misunderstandings that arise in communication.
      The role of the family, traditional healing, and nutritional considerations are
      given with some examples of home remedies. Basic cultural guidelines for use in
      assessing the patient and family are also given.

PMID- 9157899
TI  - Mobility screening as part of a community-based geriatric assessment.
AB  - This article provides an overview of the basic components of mobility and
      encourages home care practitioners to include mobility screening as a part of
      geriatric assessment. Mobility is viewed as an integrated and interdependent
      function of physical, mental, emotional, and social capacities, and therefore
      encourages an interdisciplinary approach to assessment of basic mobility problems
      and needs. The discussion includes mobility-related operational definitions and
      measurements, reasons to perform a mobility screen, how to incorporate the
      components of basic mobility into a geriatric mobility screen, and factors that
      significantly distinguish in-home assessment from a clinic- or institution-based
      geriatric mobility assessment.

PMID- 9157900
TI  - Health help. Fluid + fiber = frequency.

PMID- 9157901
TI  - Foot care for vascular patients.

PMID- 9157902
TI  - Compassionate care for dying patients.

PMID- 9157904
TI  - The home care provider in China.

PMID- 9157903
TI  - Treating patient ulcers.

PMID- 9157906
TI  - Home is different: on place and ethics.

PMID- 9157905
TI  - Opportunities are our future.
AB  - The national health care revolution is having especially important effects in
      California. Hospitals are closing, downsizing, or joining larger systems. Solo
      practice physicians are joining group practices, which in turn are being
      purchased by large for-profit physician practice organizations. Companies that
      have in the past provided a single service, such as home medical equipment, home
      infusion, hospice, or home care, are joining forces to offer many services in an
      effort to appeal to payors who would rather contract with comprehensive
      providers. Coalitions of home health agencies are forming to better compete for
      managed care contracts. Home health care agencies are merging in anticipation of
      prospective pay and the need to spread administrative costs over a wider base.
      The driving force behind this revolution? Managed care.

PMID- 9157907
TI  - On Accreditation of Health Care Organizations. The ABCs of accreditation.

PMID- 9157908
TI  - Spiritual care and the home care provider.

PMID- 9157909
TI  - Honoring the spirituality of grieving parents.

PMID- 9157910
TI  - Care after leg bypass.

PMID- 9157911
TI  - Home care, a unique nursing specialty.

PMID- 9157912
TI  - Switching from hospital-based practice to home care.

PMID- 9157913
TI  - Risk factors associated with multiple hospital readmissions.
AB  - The percentage of multiple hospital readmissions averages between 21% and 27% in
      the United States today. The reasons for this readmission rate and, more
      important, how readmissions can be prevented, are not clear. In this integrative
      review we examine 13 research articles in an attempt to identify specific factors
      leading to the readmission of medical patients. Risk factors continually
      researched throughout the articles were dependence, patient age, stage of
      illness, length of hospital stay, prior hospitalization, care after discharge,
      and mobility status. Congestive heart failure and chronic obstructive pulmonary
      disease were the medical conditions responsible for most readmissions. No single
      factor was found to universally predict readmission, although several items were
      found to be statistically significant.

PMID- 9157914
TI  - Could a multisensory approach achieve improved outcomes?

PMID- 9157915
TI  - Save your breasts and your life with monthly breast self-exams.

PMID- 9157916
TI  - A safe and healthy work environment.
AB  - Home health and hospice employers must be continually diligent in their efforts
      to prevent work-related injuries and illnesses. They have a legal and
      professional responsibility to provide employees with a workplace that is free
      from recognized hazards that cause or are likely to cause serious physical injury
      or death, and to maintain working conditions that are safe and healthful for
      their employees. This article reviews laws that affect work-related safety and
      illness. It provides guidelines for agency prevention programs regarding employee
      protection against workplace violence and infectious disease. A safe and healthy
      workplace is essential for home health and hospice employees to provide quality
      client care and for agencies to be protected from potential liability.

PMID- 9157918
TI  - Home care: an opportunity for physicians. Interview by Sarah F. Zarbock.

PMID- 9157917
TI  - Medication use in the hypothyroid patient.
AB  - Hormones produced by the thyroid gland are essential for normal growth,
      maturation, and regulation of all organ systems. In hypothyroidism, the thyroid
      gland fails to secrete adequate amounts of thyroid hormone. As a consequence
      there is a slowing of all body processes. Hypothyroidism occurs in 2% of women
      and 0.2% of men. The incidence increases with age; among people older than 60
      years of age, 6% of women and 2.5% of men have abnormal thyroid function test
      values indicative of the condition. The incidence of subclinical hypothyroidism
      may approach 15% in persons 60 years of age or older. This finding is significant
      because within 4 years of diagnosis, subclinical hypothyroidism progresses to
      overt hypothyroidism in 20% to 40% of patients.

PMID- 9157919
TI  - Partnering for success.
AB  - Almost every health care journal or newsletter I pick up has at least one article
      about the changes occurring in the health care delivery system. The changes for
      providers in all settings are enormous as we downsize, rightsize, merge, or
      simply change to meet the demands of managed care. The bottom line is that
      hospitals are shrinking and health care is moving into the outpatient and
      community environment. Those of us who are providers in any of these settings
      must respond rapidly to the changes, which are having a profound impact on the
      practice of nursing today that will continue into the future. Are nursing
      educators prepared to respond as quickly as providers to the environmental
      changes, and are they prepared to make the necessary curriculum changes to
      prepare students for their future profession? It seems more critical than ever
      for providers and educators to partner to successfully meet the current and
      future demands of the nursing profession.

PMID- 9157920
TI  - Safety first? Beyond duty.

PMID- 9157921
TI  - On accreditation of healthcare organizations. The accreditation decision: how is
      it made?

PMID- 9157922
TI  - The existence of coronary artery disease in a potential heart donor.

PMID- 9157923
TI  - Neoral: a microemulsion cyclosporine.
AB  - Cyclosporine (Sandimmune), introduced in the 1980s, improved patient and graft
      survival rates primarily by decreasing the frequency and severity of early, acute
      rejection. Today, the challenge for coordinators and clinicians is to promote
      long-term clinical stability in transplant recipients. This requires maintaining
      the cyclosporine blood level within a relatively narrow therapeutic range to
      ensure adequate and stable immunosuppression, thus reducing the risk of rejection
      caused by a suboptimal drug level or drug-related toxicity because of a level
      above the therapeutic range. However, the clinical use of Sandimmune is
      complicated by low bioavailability and highly variable pharmacokinetics that
      provide management challenges and can affect clinical outcomes adversely. Neoral,
      a new oral microemulsion formulation (in capsules and oral solution) of
      cyclosporine, improves the bioavailability and pharmacokinetics of cyclosporine
      and reduces inter- and intraindividual pharmacokinetic variability with a safety
      profile comparable to that of Sandimmune.

PMID- 9157924
TI  - Neurodevelopmental outcome of infant cardiac transplant recipients.
AB  - Normal growth and development are indicators of the success of infant cardiac
      transplantation. The clinical transplant coordinator must be aware of age
      appropriate milestones in gross motor, fine motor, language, cognitive, and
      social skills, so that accurate assessment and early intervention can be
      instituted. In this review of five cases, gross motor development was the only
      category with consistently lower scores. Gross motor development did improve in
      the two cases tested more than once. Length of hospitalization before and after
      transplantation and use of sedative medications during the waiting period may
      have affected developmental outcome scores.

PMID- 9157925
TI  - Critical pathways as an effective tool to reduce cardiac transplantation
      hospitalization and charges.
AB  - A critical pathway is a component of managed care focusing on outcome-oriented,
      cost-effective care. This retrospective review of 74 cardiac transplants in 72
      patients evaluated the influence of critical pathways on clinical management,
      length of hospitalization, and hospital charges. Transplant patients were divided
      into group 1 (n = 51), which received standard primary nursing care, and group 2
      (n = 23), which received nursing case management using a critical pathway. The
      number of intensive care unit days for group 2 was significantly smaller than for
      group 1, as were duration of hospitalization and hospital charges. The critical
      pathway provided for systematic delivery of care and decreased length of
      hospitalization and charges without compromising safety or quality.

PMID- 9157926
TI  - Relationship between hope and self-esteem in renal transplant recipients.
AB  - In the transplant community great emphasis is placed on health and well-being.
      Because hope and self-esteem are linked with a positive health outcome, knowledge
      of transplantation should include an understanding of the extent to which hope is
      influenced by self-esteem. Few researchers have addressed the topic of hope and
      its impact on self-esteem; therefore, we sought to ascertain whether a
      relationship exists between hope and self-esteem in renal transplant recipients.

PMID- 9157927
TI  - Incidence and treatment of recurrent hepatitis C after liver transplantation.
AB  - Recurrence of hepatitis C is a significant problem after liver transplantation.
      This prospective study was done to assess the rate of recurrence and discuss two
      possible treatment modalities that have been successful in avoiding
      retransplantation. Twenty-one patients underwent orthotopic liver transplantation
      for hepatitis C at a metropolitan medical center over a 34-month period. The mean
      follow-up interval was 13.4 +/- 2.2 months (range 5-28 months). The patients were
      routinely evaluated with clinic visits and liver function tests, specifically
      total bilirubin, serum glutamic-oxaloacetic transaminase, and gamma-glutamyl
      transpeptidase. If values were elevated, the patient was admitted to the hospital
      for liver biopsy. Ten of the 21 patients demonstrated recurrence on biopsy. Two
      of 10 patients required no therapy. Interferon A was initiated in the remaining
      eight. Three of the eight patients had no significant response to interferon and
      were given intravenous ribavirin under an experimental protocol. Two of these
      three showed significant improvement in liver function values. The third died of
      chronic rejection. The incidence of recurrent hepatitis C after liver
      transplantation is significant. Many centers have had to resort to
      retransplantation. Our results show that with early detection and aggressive
      treatment with interferon and ribavirin, hepatitis C can be controlled and
      retransplantation may be avoided.

PMID- 9157928
TI  - Evaluating a successful coroner protocol.
AB  - The coroner release rates for the service of a particular organ procurement
      organization were evaluated through a retrospective analysis, which included the
      year before (1991), the year during (1992), and the year after (1993) the
      adoption of a formal protocol for coroner's cases. In 1991, 22 of 55 (40%)
      coroner cases were denied for donation by the coroner. In 1992 and 1993, 12 of 55
      (22%) and 9 of 56 (16%) coroner cases, respectively, were denied for donation.
      More significantly, in 1991, 4 of 6 (67%) cases of homicidal gunshot wound to the
      head were denied for donation by the coroner, whereas only 1 of 13 (8%) such
      cases were denied in 1993. Also in 1991 all closed head injuries (two) from falls
      were denied for donation by the coroner, whereas in 1993 1 of 8 (12%) closed head
      injuries was denied for donation. Finally, all 4 of 4 nonaccidental traumas (ie,
      child abuse) were denied in 1991, but 1 of 2 were released in both 1992 and 1993.
      Further education and awareness efforts could reduce the rates of coroner denial
      even more significantly.

PMID- 9157929
TI  - Increasing referrals and donations using the Transplant Center Development Model.
AB  - Although transplantation centers directly benefit from organ and tissue donation,
      they continue to yield low organ and tissue referral and donation rates. Our
      medical center and organ procurement organization developed a model to increase
      referral and donation rates. This model, called the Transplant Center Development
      Model, facilitates the donation process, specializes staff education, and
      promotes administrative involvement. After it was was implemented at our medical
      center in 1991, the referral and donation rates from 1988 to 1990 were compared
      with those from 1991 to 1993. The results showed that after implementation of the
      model, the organ referral mean increased 47%; the organ donation mean, 50%; and
      the tissue donation mean, 117%. These findings suggest that this model may be a
      valuable tool in transplant center development.

PMID- 9157930
TI  - Factors influencing organ placement efforts in donors with brain tumors.
AB  - A 3-year retrospective review of brain tumor cases was performed to determine
      factors that influence organ procurement in light of the increase in references
      in transplant literature to the hazards of transplanting organs from donors with
      brain tumors. A 3-year review of cases in which organ procurement efforts
      occurred were evaluated. Of 314 cases resulting from this review, organ
      procurement efforts yielded 10 patients with a diagnosis of brain tumor. Of those
      10 cases, seven progressed to organ donation, with at least one organ per patient
      recovered. Manipulation of brain tumors or manipulation along with tissue
      diagnosis does not seem to hinder procurement of organs. Without tissue
      diagnosis, the ability of the organ procurement organization to place organs
      decreases significantly.

PMID- 9157931
TI  - Assessment of organ acquisition costs for an Australian public health system.
AB  - Available data on the cost of organ acquisition in Australia's socialized public
      health systems are minimal. The purpose of this study was to determine the cost
      for organ acquisition by a state transplant service, and to provide (1) an
      assessment of acquisition costs within one Australian public health system, (2) a
      baseline for future cost assessments, and (3) an indication of cost-effectiveness
      in international terms. Between July and December 1993, 51 kidneys, 21 livers,
      and 15 hearts were provided for transplantation in the system. Data collected
      during this period were used to calculate the acquisition cost for each
      transplanted organ. Direct and indirect costs were included in the calculations.
      The distribution of costs incurred for organ acquisition were direct, 67%;
      indirect, 14%; and organ-specific, 19%. Of the total direct costs, aircraft
      charter accounted for 75%, or 50% of the total acquisition costs. The provision
      of an organ by a donor coordination service accounted for 20% of the total costs,
      or a mean of A$783 (US$563) per organ. This study provides a baseline for organ
      acquisition cost in the Australian healthcare system. The geographic and
      demographic nature of Australia imposes the largest single cost factor (i.e., air
      charter), which highlights the need for alternative retrieval and transport
      systems of organs wherever possible. The acquisition costs reported in this study
      indicate that the system is cost-effective in international terms.

PMID- 9157932
TI  - 20th Annual meeting, North American Transplant Coordinators Organization--Boston,
      August 2, 1995.

PMID- 9157933
TI  - Case management of chronic ventilator patients. Reduce average length of stay and
      cost by half.
AB  - The implementation of the case management model and the use of critical pathways
      has become a major strategy to improve quality of care and cope with measuring
      and managing costs. Grant Medical Center, a 640-bed Level I Trauma Center, began
      case managing its chronic ventilator patients in July, 1993. A 30-day critical
      pathway was developed using a multidisciplinary team approach. In case managing
      these patients, many problematic issues were identified, such as lack of adequate
      involvement by staff experienced in specific disciplines and multiple physician
      decision makers for each case. By increasing multidisciplinary collaboration,
      care of these patients was systematically changed and streamlined. Over a 2-year
      period, the average length of stay for chronic ventilator patients decreased from
      74.5 days to 41.9 days, and the average cost per case decreased from $189,080 to
      $107,019.

PMID- 9157934
TI  - Managed care contracts. A guide for clinical case managers.
AB  - When healthcare executives speak of managed care, they often use the term
      generically to refer to any arrangement with a healthcare payer other than
      traditional fee-for-service reimbursement. All too often, the "management" aspect
      is missing from managed care, resulting in an arrangement that could more aptly
      be described as "discounted care." This lack of clinical representation is
      unfortunate, since there are numerous issues that have an impact on clinical
      care, including choice of referral providers, noncoverage of certain procedures
      or treatments, and similar issues that may influence the patient's plan of care.
      Organizations that approach managed care as a system that blends the resources of
      management, finance, and clinicians, will enjoy the greatest potential for
      success. With their practical experience and insight into the administrative and
      clinical issues that may be encountered, nurse case managers will ultimately be
      responsible for managing the care of the contracted population. As case managers
      are the vital link among payers, providers, patients, and families, it is
      essential that the case manager understand managed care concepts, be conversant
      in the terminology of managed care, function as a member of the team responsible
      for evaluating contracts, and periodically review existing arrangements. This
      article presents an overview of the managed care contract development process,
      and provides tools to enable the nurse case manager to participate in the
      contracting process.

PMID- 9157935
TI  - Developing performance data for health care management.

PMID- 9157936
TI  - The ABCs of case management. A review of the basics.
AB  - As managed care continues to emerge as a dominant structure for delivering and
      reimbursing health care, nursing is responding and assisting in reshaping the
      health care system. Nursing case management as a new delivery of care includes
      providing and coordinating care across the continuum. The continuum includes
      prevention, wellness, acute, rehabilitation, long term, and hospice care. Various
      definitions of case management exist and are dependent on the discipline that
      employs them, the setting in which they are implemented, and the personnel and
      staff mix used in their implementation. Patient identification, assessment,
      planning, implementing and coordinating and evaluating the delivery of service
      and patient outcomes are components common to all case management models. The
      nurse case manager should be minimally educationally prepared at the
      baccalaureate level. She/he should also have expert clinical skills, knowledge of
      the health care system, health care finances, and legal issues and be an
      effective communicator. Within the case management model the case manager will
      use various tools to achieve clinical, quality, and economic outcomes. Some of
      these tools include practice guidelines, critical paths, variance analysis,
      protocols/algorithms, risk assessment, and outcome measurement tools.

PMID- 9157937
TI  - Laminectomy: an outpatient approach.

PMID- 9157938
TI  - Information systems tools available to the case manager.
AB  - Regardless of the setting, the role of the nurse as a manager of care continues
      to grow and develop. The nurse case manager needs to have vital information
      readily available to facilitate critical thinking, analysis, and decision-making
      on the appropriateness of care provided to patients and to ensure that optimal
      outcomes are achieved. While there are a variety of clinical information systems
      available, it is evident that the complexity of the case manager's information
      needs presents challenges for software developers. Accordingly, nurse case
      managers must take an active role in defining and communicating their needs. The
      purpose of this article (the first of two) is to present a general overview of
      the information needs of the nurse case manager and the computerized information
      system tools available (and emerging) to meet these needs. A follow-up article in
      the next issue of Nursing Case Management will focus on a typical clinical
      information system selection process; outline specific ways the nurse case
      manager can effectively influence that process; and provide a checklist that will
      enable the nurse case manager to assist the institution in selecting and
      implementing the most appropriate system.

PMID- 9157939
TI  - Eight strategies to acquire physician support in case management.

PMID- 9157940
TI  - Managing variances in case management.
AB  - Timely management of variances is vital for cost effective patient care. A
      multifaceted approach that involves the healthcare team, patient, and family
      facilitates the identification and management of variances as they occur. The
      critical path can be used to monitor variances that influence fiscal outcomes in
      select patient populations. Strategies are described that can be used to monitor
      and manage variances, including developing a mechanism for monitoring and
      managing variances, implementing that mechanism, and evaluating the process for
      usability. Monitoring variances includes choosing tools that will be used and
      staff who will assume primary responsibility, and initiating an outcome analysis
      program. Managing variances comprises organizing an interdisciplinary committee,
      establishing a communication plan, creating strategies, and using continuous
      quality improvement teams.

PMID- 9157941
TI  - Association of the fatty acid composition of serum phospholipids with hemostatic
      factors.
AB  - It has been suggested that the fatty acid composition of serum phospholipids is
      an independent risk factor for cardiovascular disease. We examined the
      association of the fatty acid composition of serum phospholipids with fibrinogen,
      factor VII antigen (FVII:Ag), factor VII coagulant activity (FVII:C),
      plasminogen, and lipoprotein(a) [Lp(a)] in 338 men and 363 women 45 to 64 years
      old. Palmitic acid, the most abundant saturated fatty acid, was positively
      associated in univariate analyses with plasminogen, which explained 5.2% of its
      variance among men (P<.0001) and 5.8% among women (P<.0001). Linoleic acid, which
      is the most abundant polyunsaturated fatty acid, was negatively associated with
      plasminogen and fibrinogen. This explained 1.1% of the variance in fibrinogen
      among men (P=.04) and 3.2% among women (P=.0006) and 4.1% of the variance in
      plasminogen in both sexes (P<.0001). Dihomogammalinolenic acid was positively
      associated with FVII:Ag and explained 3.7% of its variance among men (P=.0003)
      and 4.6% among women (P<.0001). Furthermore, dihomogammalinolenic acid was
      positively and significantly associated with FVII:C, fibrinogen, and plasminogen
      among women but not among men. All these associations remained significant after
      adjustment for multiple potential confounding factors such as age, smoking, serum
      lipids, and body mass index. In conclusion, our findings suggest that linoleic
      acid, palmitic acid, and dihomogammalinoleic acid are significant independent
      determinants of hemostatic profile. It is not clear, however, to what extent
      these results reflect the effects of fatty acids on coagulation and to what
      extent they reflect the activity of inflammatory processes in the arteries.

PMID- 9157942
TI  - Fibrinolytic function after dietary supplementation with omega3 polyunsaturated
      fatty acids.
AB  - Hypertension is associated with derangements in glucose and lipid metabolism.
      Increased levels of plasminogen activator inhibitor type 1 (PAI-1) are thought to
      potentiate the development of coronary events in this condition. Fish oil (omega3
      polyunsaturated fatty acids [PUFAs]) have lipid-lowering effects, but the
      cardioprotective potential has been questioned because fish oil has been found to
      increase PAI-1 activity. This study was performed to determine the effects of
      omega3 PUFAs on the fibrinolytic function in hypertension. Seventy-eight persons
      with untreated hypertension were included in a 16-week, double-blind, randomized,
      controlled intervention study with 4 g/d of eicosapentaenoic and docosahexaenoic
      acids or corn oil placebo. Plasma PAI-1 activity, tissue plasminogen activator
      (tPA) activity, levels of fibrinogen and factor VII(c), and platelet count were
      measured before and after intervention (mean+/-SE). PAI-1 activity changed
      similarly in the fish oil and corn oil groups (1.8+/-1.0 U/mL versus 3.5+/-1.2
      U/mL, P=.25), as did tPA (-0.02+/-0.02 IU/mL versus -0.13+/-0.03 IU/mL, P=.28),
      levels of factor VII(c) (6+/-5% versus 5+/-4%, P>.3), and platelet count (2+/
      7x10(9)/L versus 3+/-5x10(9)/L, P>.3). None of these variables changed from
      pretreatment levels during fish oil intake. Fibrinogen levels increased
      significantly both during fish oil (0.6+/-0.1 g/L, P=.0001) and corn oil (0.4+/
      0.1 g/L, P=.002) intake. There was no between-group difference (P>.3). In
      conclusion, a daily intake of 4 g omega3 PUFAs does not affect PAI-1 and tPA
      activity in persons with hypertension. A modest increase in fibrinogen levels was
      observed after both fish oil and corn oil intake.

PMID- 9157943
TI  - Associations between diet and the hyperapobetalipoproteinemia phenotype
      expression in children and young adults: the Cardiovascular Risk in Young Finns
      Study.
AB  - The effect of diet on blood lipids has been under intensive study during recent
      decades. However, diet in the context of the hyperapobetalipoproteinemia
      (hyperapoB) phenotype has received less attention. The hyperapoB phenotype is
      commonly encountered in patients with premature coronary heart disease. It is
      defined as a combination of an increased concentration of apolipoprotein B (apo
      B), a normal concentration of LDL cholesterol (LDL-C), and as a result, a low LDL
      C/apo B ratio. We studied the associations between diet and blood lipids in a
      cohort of 534 children and young adults 9 to 24 years old. The ratio of
      polyunsaturated to saturated fats (P/S ratio) correlated (r=-0.19, P<.001) with
      the LDL-C/apo B ratio. This association was also found when the model was
      adjusted with triglycerides (r=-0.24, P<.001). A change in the P/S ratio from
      0.10 to 0.60 corresponded to a decrease of 0.12 in the LDL-C/apo B ratio, and in
      the highest apo B decile, the P/S value was higher in hyperapoB individuals
      (0.33) than in others (0.28, P=.019). Our results imply that the fatty acid
      composition of the diet may be one of the environmental factors that influence
      the hyperapoB phenotype expression.

PMID- 9157944
TI  - Differences in the phenotype between children with familial defective
      apolipoprotein B-100 and familial hypercholesterolemia.
AB  - Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited genetic
      disorder resulting from a point mutation in the apolipoprotein (apo) B gene and
      is associated with significantly elevated plasma total and LDL cholesterol
      levels. Despite numerous descriptions outlining the phenotype of children with
      familial hypercholesterolemia (FH), no study has described the biochemical and
      clinical phenotype in a cohort of children with FDB. The phenotypes of FH and
      FDB, therefore, have not been compared in children. We have studied a cohort of
      38 Dutch children (all <20 years old) with FDB from 21 different families. Lipid
      and lipoprotein levels and the clinical phenotype were compared with 97 age
      matched FH heterozygotes, as defined by molecular analysis, and with age-matched
      non-FDB, non-FH control subjects. Female FDB carriers (n=23) had significantly
      lower total cholesterol (P<.001), LDL cholesterol (P=.001), total cholesterol:HDL
      ratio (P<.001), and apoB levels (P=.001) than age-matched female FH heterozygotes
      (n=50). Similar results were noted in male FDB carriers (n=15) compared with male
      FH heterozygotes (n=47; P=.005, P=.007, P=.014, and P=.074, respectively). Within
      the FDB group, female FDB heterozygotes had higher LDL cholesterol (P=.038) and a
      trend to higher total cholesterol levels (P=.165) than age-matched males. Both
      male and female FDB carriers had significantly higher total cholesterol, LDL
      cholesterol, and total cholesterol:HDL ratio than age- and sex-matched control
      subjects, which was evident even in children <10 years of age, providing
      additional evidence that this mutation is penetrant in early life. These results
      provide evidence for a milder biochemical phenotype in children with FDB than in
      children with FH. The phenotype observed is intermediate between that of control
      subjects and FH heterozygotes matched for age and sex. As the incidence of
      coronary artery disease is related to both the extent and duration of cholesterol
      elevation, our findings might explain in part the lower incidence of clinical
      atherosclerosis seen in adults with this condition than in adults with FH.

PMID- 9157945
TI  - Segregation analysis of plasma apolipoprotein B levels in familial combined
      hyperlipidemia.
AB  - Familial combined hyperlipidemia (FCH) is a heritable lipid disorder that is
      associated with an increased risk of premature cardiovascular disease. An
      elevated plasma apolipoprotein (apo) B concentration is reported to be a
      diagnostic feature of the disorder. Recently we demonstrated a strong relation
      between plasma apoB concentrations and the cholesterol concentration in VLDL plus
      LDL, both elevated in FCH families. Therefore, examination of the inheritance of
      elevated plasma apoB levels in FCH families may reveal important information
      about the mechanism responsible for the aggregation of elevated plasma lipids in
      FCH. This study included 663 Dutch family members in 40 families ascertained
      through FCH probands. Plasma apoB concentration correlated significantly with
      apoB-related cholesterol both in the probands and the relatives (r=.83 and r=.90,
      respectively). Adjustment for age, sex, body mass index, and smoking habits
      accounted for 35.7% of the variation in apoB levels, and there was strong
      familial aggregation in adjusted apoB levels in these families. Complex
      segregation analysis was performed to determine the mechanism of inheritance
      behind this familial aggregation. The aggregation of elevated apoB levels was
      best explained by a major gene effect inherited by a codominant mechanism.
      Estimated mean apoB levels for the three supposed genotypes AA, AB, and BB were
      111.5, 126.7, and 165.7 mg/dL, respectively, with relative frequencies of 43.5%,
      44.9%, and 11.6%, respectively. In conclusion, despite assumed metabolic and
      genetic heterogeneity of FCH, there is clear evidence for a single gene effect on
      apoB concentrations in families ascertained through FCH. Linkage studies based on
      this analysis may further clarify the molecular basis of the apoB regulation in
      these families.

PMID- 9157946
TI  - No evidence of linkage between familial combined hyperlipidemia and genes
      encoding lipolytic enzymes in Finnish families.
AB  - Familial combined hyperlipidemia (FCHL) is characterized by different lipid
      phenotypes (IIa, IIb, IV) and elevated apolipoprotein B (apo B) levels in
      affected family members. Despite intensive research, the genes involved in the
      expression of this complex disorder have not been identified, probably because of
      problems associated with phenotype definition, unknown mode of inheritance, and
      most probably genetic heterogeneity. To explore the genetics of FCHL in the
      genetically homogeneous Finnish population, we collected 14 well-documented
      Finnish pedigrees with premature coronary heart disease and FCHL-like
      dyslipidemia. The lipolytic enzymes lipoprotein lipase (LPL), hepatic lipase
      (HL), and hormone-sensitive lipase (HSL) were selected as initial candidate genes
      because of their central roles in apo B and triglyceride metabolism. On the basis
      of the pedigree structures, a dominant mode of inheritance was adopted for
      linkage analyses, and serum total cholesterol and/or triglyceride levels
      exceeding the 90th percentile level were set as diagnostic criteria (criterion
      1). In pairwise linkage analyses with intragenic markers, no evidence for linkage
      was found. Instead, the significantly negative LOD scores suggested exclusion of
      all three loci for single major gene effect. LOD scores were -14.63, -5.03, and 
      5.70 for the three LPL polymorphisms (theta=0.00); -9.40, -6.30, and -4.74 for
      the three HL polymorphisms (theta=0.00); and -15.29 for the HSL polymorphism
      (theta=0.00). The results were very similar when apo B levels over the 90th
      percentile were used as criteria for affected status (criterion 2). Also, when
      linkage calculations were carried out using an intermediate or recessive mode of
      inheritance, the results of pairwise linkage analysis remained negative.
      Furthermore, when haplotypes were constructed from multiple polymorphisms of the
      LPL and HL genes, no segregation with the FCHL phenotype could be observed in the
      14 Finnish families. Data obtained by the affected sib-pair method supported
      these findings, suggesting that the LPL, HL, or HSL genes do not represent major
      loci influencing the expression of the FCHL phenotype.

PMID- 9157947
TI  - Five frequent polymorphisms of the PAI-1 gene: lack of association between
      genotypes, PAI activity, and triglyceride levels in a healthy population.
AB  - The main function of plasminogen activator inhibitor type 1 (PAI-1) is to
      decrease fibrinolysis, which leads to fibrin accumulation. An elevated plasma PAI
      1 concentration has been identified as a risk factor for the development of
      myocardial infarction, and an association between 1 polymorphism of the PAI-1
      promoter and plasma PAI-1 levels has been described. Our aim was to identify new
      polymorphisms in the PAI-1 gene and to further examine the relationship between
      PAI-1 genotypes and circulating PAI-1 levels. We report the presence of 4 new
      polymorphisms that were identified by non-isotopic single-strand conformational
      polymorphism analysis followed by sequencing. These polymorphisms were
      investigated in relation to PAI-1 levels in a sample of 256 healthy men, aged 50
      59 years, from France and Northern Ireland. Two G/A substitutions were detected
      at positions -844 and +9785. The former is in strong positive linkage
      disequilibrium with the previously described 4G/5G polymorphism at position -675.
      Two polymorphisms in the 3' untranslated region were identified. One corresponds
      to a T/G substitution at position +11,053 and is in negative linkage
      disequilibrium with the G/A substitution (+9785). The other is a 9-nucleotide
      insertion/deletion located between nucleotides +11,320 and +11,345 in a threefold
      repeated sequence. This polymorphism is in strong positive linkage disequilibrium
      with the G/A substitution (+9785). The overall heterozygosity provided by the 5
      PAI-1 polymorphisms (including the 4 new variants and the 4G/5G polymorphism) was
      .77. No significant association was found between PAI activity and genotypes;
      furthermore, the well known associations between PAI activity and body mass
      index, serum triglycerides, or insulin were homogeneous according to PAI-1
      genotypes.

PMID- 9157948
TI  - Shared and unique genetic effects among seven HDL phenotypes.
AB  - The purpose of this study was to investigate the genetic control of various HDL
      measures and to determine the proportion of genetic variance explained by shared
      genes (ie, pleiotropy) and the proportion unique to each trait. The data used
      were drawn from large, randomly ascertained pedigrees of Mexican Americans
      participating in the San Antonio Family Heart Study. Data were available for 655
      individuals (258 men and 397 women) in 26 families. We performed a multivariate
      quantitative genetic analysis to simultaneously estimate both the additive
      genetic and random environmental correlations among seven HDL phenotypes. These
      seven HDL phenotypes can be divided into two categories: measures of
      concentration and estimates of particle size. Concentration was measured for apo
      A-I, apo A-II, esterified cholesterol, and unesterified cholesterol, and particle
      size was estimated for apo A-I, apo A-II, and esterified cholesterol. The
      heritabilities (h2) for each of the seven traits were significantly greater than
      zero (P<.05) and ranged from 0.2 to 0.6. When considered in a pairwise fashion,
      all combinations of these traits showed marked genetic correlations (rho(G)=0.33
      to 0.87) and all were significantly greater than zero (P<.05), indicative of
      pleiotropic effects. However, we found substantial unique genetic variance for
      each of these traits even after accounting for the effects shared in common with
      all the remaining measures. We conclude that the genetic variation in these HDL
      phenotypes is a result of the action of common as well as unique genes.

PMID- 9157949
TI  - The apolipoprotein E2 (Arg145Cys) mutation causes autosomal dominant type III
      hyperlipoproteinemia with incomplete penetrance.
AB  - Type III hyperlipoproteinemia (type III HLP) is an atherogenic disorder of
      lipoprotein metabolism characterized by the accumulation of cholesterol-enriched
      VLDL and is usually associated with homozygosity for a normal variant of apoE,
      apoE2. ApoE2(Arg145Cys) is a rare variant arising from a C-->T transition at
      nucleotide 4031 and has been linked to type III HLP. Ten subjects from a group of
      42 unrelated individuals with proven type III HLP were found to be either
      heterozygous or homozygous for the apoE2(Arg145Cys) mutation by DNA sequencing.
      The apoE4-Philadelphia (Glu13Lys, Arg145Cys) variant was subsequently excluded.
      None of 4 homozygotes (3 blacks and 1 of mixed ancestry) developed ischemic heart
      disease, but they did present with xanthomata. In contrast, 6 heterozygous
      subjects presented mainly with ischemic heart disease but generally lacked
      physical signs. Cholesterol concentrations ranged from 6.2 mmol/L to 13.3 mmol/L
      and triglyceride levels from 3.2 to 13.2 mmol/L. The dyslipoproteinemia in
      homozygous and heterozygous subjects was indistinguishable. Family investigation
      identified an additional 10 heterozygous mutant-allele carriers, of whom 3 had
      type III HLP. This unique cohort of patients indicates that the apoE2(Arg145Cys)
      mutation is relatively common in several population groups in our region and may
      be particularly prevalent in blacks. There was no clear allele dosage effect
      present for the development of dyslipoproteinemia or atherosclerosis. The mode of
      inheritance is for the first time clearly established to be autosomal dominant
      with incomplete penetrance.

PMID- 9157950
TI  - Subjects with ApoA-I(Lys107-->0) exhibit enhanced fractional catabolic rate of
      ApoA-I in Lp(AI) and ApoA-II in Lp(AI with AII).
AB  - Our purpose was to examine HDL metabolism in a Finnish kindred with a 3-bp
      deletion in the apolipoprotein (apo) A-I gene, resulting in a deletion of Lys107
      in the mature apoA-I. Patients with this mutation [apoA-I(Lys107-->0)] have
      reduced plasma HDL cholesterol and lipoprotein (AI with AII) [Lp(AI w AII)]
      concentrations, but not Lp(AI) levels, compared with unaffected family members.
      Using primed constant infusions of [5,5,5-2H3]leucine, we determined the
      residence time (RT) and absolute production rate (APR) of apoA-I and apoA-II
      entering plasma in two subpopulations of HDL particles: [Lp(AI) and Lp(AI w AII)]
      in three patients heterozygous for apoA-I(Lys107-->0) and in seven healthy
      control subjects. In patients, the mean RT of apoA-I in Lp(AI) (3.75+/-1.68 days)
      was less than half that observed in control subjects (8.01+/-2.51 days, P<.05).
      The mean RT of apoA-I in Lp(AI w AII) was also lower in patients than in control
      subjects, but differences were not statistically significant (4.72+/-2.42 versus
      6.50+/-2.19 days). The mean RT of apoA-II in Lp(AI w AII) was significantly lower
      in patients (5.24+/-1.65 days) than in control subjects (9.64+/-3.57 days,
      P<.05). The APR of apoA-I into Lp(AI) was twofold higher in patients (5.9+/-2.1
      mg x kg(-1) x d(-1)) than in control subjects (2.5+/-0.9, P<.05). The APRs of
      apoA-I and apoA-II into Lp(AI w AII) were similar in patients and control
      subjects. Our results are consistent with the concept that patients heterozygous
      for the apoA-I(Lys107-->0) mutation have enhanced fractional catabolism of apoA-I
      and apoA-II in both HDL subspecies, especially in Lp(AI), and an increase in apoA
      I production only into Lp(AI), which may be compensatory. Therefore, only their
      Lp(AI w AII) levels are decreased.

PMID- 9157951
TI  - Decreased production and increased catabolism of apolipoprotein B-100 in
      apolipoprotein B-67/B-100 heterozygotes.
AB  - Apolipoprotein (apo) B-67 is a truncated form of apoB-100 due to deletion of an
      adenine at cDNA 9327. Heterozygotes have one allele making apoB-100; therefore,
      plasma apoB levels would be predicted to be at least 50% of normal. However, apoB
      67 heterozygotes have total plasma apoB levels that are 24% of normal. To
      determine the mechanisms responsible for the lower-than-expected levels of apoB,
      in vivo kinetics of apoB-100 were performed in three apoB-67/apoB-100
      heterozygotes and compared with those of six control subjects by using a primed
      constant infusion of [5,5,5-2H3]leucine in the fed state. Kinetic parameters were
      calculated by multicompartmental modeling of the data. The mean total apoB plasma
      concentration of the apoB-67 subjects was 21.8+/-6.1 mg/dL, or 24% of that of
      control subjects (89.6+/-24.1 mg/dL, P=.002). ApoB-67 subjects had lower mean
      VLDL apoB-100 production rates (3.6+/-1.2 versus 13.9+/-3.5 mg x kg(-1) x d(-1),
      P=.002) and lower mean transport rates of apoB-100 into LDL (3.5+/-1.4 versus
      12.6+/-4.1 mg x kg(-1) x d(-1), P=.008) compared with control subjects. The
      transport rate into IDL was not significantly different (1.2+/-0.5 versus 6.2+/
      4.0 mg x kg(-1) x d(-1), P=.07). The fractional catabolic rate of VLDL apoB-100
      was significantly higher in apoB-67 subjects than in control subjects (18.1+/-8.6
      versus 7.6+/-1.6 mg x kg(-1) x d(-1), P=.017). ApoB-100 IDL and LDL fractional
      catabolic rates were not significantly different. VLDL apoB-100 pool size in apoB
      67 subjects was 11% of that of control subjects (15.8+/-7.7 versus 141.6+/-33.7
      mg, P=.0004) due to a 74% lower production rate (26% of control values) and a 2.4
      fold higher fractional catabolic rate. LDL apoB-100 pool size in apoB-67 subjects
      was 22% of that of control subjects (665.3+/-192.4 versus 2968.3+/-765.2 mg,
      P=.002) due primarily to a lower production rate (27% of control values). Thus,
      both decreased production of VLDL and LDL apoB-100 and increased catabolism of
      VLDL apoB-100 are responsible for the low levels of apoB-100 in apoB-67 subjects.

PMID- 9157952
TI  - Effective lowering of plasma, LDL, and esterified cholesterol in LDL receptor
      knockout mice by adenovirus-mediated gene delivery of ApoB mRNA editing enzyme
      (Apobec1).
AB  - Adenovirus-mediated gene delivery of apolipoprotein (apo)B mRNA editing enzyme
      (AvApobec1) was used to study the effect of apoB mRNA editing on apoB production
      in homozygous LDL receptor-deficient (LDLR-/-) mice. Intravenous injection of
      AvApobec1 into these mice resulted in a >80% decrease in plasma apoB-100 with a
      concomitant increase in plasma apoB-48 level. The plasma apoE level also
      increased. In all cases, total plasma apoB (apoB-100 + apoB-48) decreased by 60%
      at day 5 and remained approximately 40% lower in AvApobec1-treated compared with
      control vector Av1LacZ4-treated animals at day 12. On day 12, total plasma
      cholesterol decreased by 29% in male mice and 18% in female mice that were
      transduced with AvApobec1. This was reflected in a reduction in apoB-containing
      lipoprotein cholesterol, which decreased by 34% and 27% in male and female mice,
      respectively. Apobec1 gene transfer also decreased the cholesteryl ester contents
      in the LDL fraction, which were 16%, 22%, and 22% in female and 20%, 20%, and 15%
      in male animals on days 5, 7, and 12, respectively, compared with Av1LacZ
      controls with 29%, 32%, and 33%, respectively, in female and 29%, 38%, and 36%,
      respectively, in male animals. Nondenaturing gradient gel electrophoresis
      indicated almost complete elimination of LDL particles of 29, 27, and 25 nm at
      days 7 and 12. We conclude that in the absence of a functioning LDL receptor,
      hepatic overexpression of Apobec1 is highly efficient in lowering plasma apoB-100
      levels, leading to the almost complete elimination of LDL particles and a
      reduction in LDL cholesterol and cholesteryl ester content.

PMID- 9157953
TI  - Adenovirus-mediated transfer of a dominant-negative H-ras suppresses neointimal
      formation in balloon-injured arteries in vivo.
AB  - Abnormal migration and proliferation of arterial smooth muscle cells may be a
      central event in inflammatory proliferative arterial diseases such as
      atherosclerosis and restenosis after angioplasty. The proto-oncogene c-H-ras is
      considered to be a key transducer in various growth-signaling events. We
      constructed an adenoviral vector (AdexCAHRasY57) expressing a potent dominant
      negative mutated form of c-H-ras in which tyrosine replaces aspartic acid at
      residue 57. Infection of smooth muscle cells with AdexCAHRasY57 produced a large
      quantity of H-ras-p21, completely inhibited serum-stimulated activation of
      mitogen-activated protein kinase, and abolished the DNA synthesis in response to
      serum mitogens. However, a surge of intracellular Ca2+ concentration in response
      to platelet-derived growth factor was not affected, suggesting that some cellular
      functions were preserved. When we applied AdexCAHRasY57 into balloon-injured rat
      carotid arteries from inside the lumen, neointimal formation was significantly
      reduced (neointima/media ratio: 0.28) compared with that (1.50) in arteries
      treated with either injury alone or injury and infection with a control
      adenovirus, AdexCALacZ, expressing bacterial beta-galactosidase. Our results
      suggest that adenovirus-mediated arterial transfer of dominant-negative H-ras may
      be a practical form of effective molecular intervention for proliferative
      arterial diseases.

PMID- 9157954
TI  - In vivo transfer of lipoprotein(a) into human atherosclerotic carotid arterial
      intima.
AB  - The aim of this study was to compare the atherogenic potential of lipoprotein(a)
      [Lp(a)] and LDL by measuring the intimal clearance of these two plasma
      lipoproteins in the atherosclerotic intima of the human carotid artery in vivo.
      Autologous 131I-Lp(a) and 125I-LDL were mixed and reinjected intravenously 3
      hours before elective surgical removal of the arterial intima in four patients.
      The intimal clearance of Lp(a) and LDL was 229+/-48 and 405+/-127 nL/cm2 per
      hour, respectively (paired t test; P=.12). The mass accumulation of Lp(a) (114+/
      32 ng/cm2 per hour) was on average one 15th that of LDL (paired t test; P=.06),
      mainly reflecting a low plasma concentration of Lp(a) compared with LDL in the
      human subjects studied. In accordance with our previous observation in rabbits,
      there was a positive association between the intimal clearance of LDL and that of
      Lp(a) (r=.97, P=.03). Accordingly, high plasma levels of Lp(a) may share with LDL
      the potential for causing lipid accumulation in the arterial intima in humans.

PMID- 9157955
TI  - Do plaques grow upstream or downstream?: an angiographic study in the femoral
      artery.
AB  - Although the distribution of atherosclerosis has been described, little is known
      about the direction of growth of plaques. In this study, 237 patients with slight
      or moderate atherosclerosis underwent femoral angiography twice at a 3-year
      interval, and the films were studied with computerized image analysis. First,
      atherosclerosis was measured as edge roughness, and the change in roughness of
      each 1-cm segment over the 3-year period was related to the edge roughness of the
      segments immediately upstream and downstream. On the medial side of the artery,
      the change in edge roughness was found to be more strongly related to the
      roughness values upstream than to those downstream of the segment studied. This
      suggests that growth in the downstream direction is more common than growth in
      the upstream direction. On the lateral side, more equivocal results were
      obtained. Atherosclerosis was also assessed by study of the cross-sectional area
      of the artery as a function of distance along the vessel. A mathematical model of
      plaque growth was formulated as a nonlinear filtering of this curve. Growth in
      the downstream direction was significantly (P<.001) more frequent than growth in
      the upstream direction. The findings are compatible with an atherogenic effect of
      fluid mechanical disturbances, such as flow separation, that may occur downstream
      of a stenosis.

PMID- 9157956
TI  - Relative involvement of GPIb/IX-vWF axis and GPIIb/IIIa in thrombus growth at
      high shear rates in the guinea pig.
AB  - The relative involvement of the glycoprotein (GP) Ib/IX-von Willebrand factor
      (vWF) axis and GPIIb/IIIa in thrombus growth at high shear rates was assessed and
      compared by testing the pharmacological effects of VCL, a recombinant GPIb
      binding fragment of vWF (residues 504-728), aurintricarboxylic acid (ATA), which
      binds to the 509-695 disulfide loop of vWF, and lamifiban, a specific synthetic
      GPIIb/IIIa antagonist. In vivo, their effects were evaluated in guinea pig
      mesenteric arteries, in a model of a laser-induced cyclic thrombotic process, and
      ex vivo, at a shear rate of 1800 s(-1), in a capillary perfusion chamber model,
      in which collagen-adherent platelets are exposed to nonanticoagulated guinea pig
      blood. In vivo, VCL, ATA, and lamifiban administered 2 minutes after intimal
      injuries stopped thrombus growth, prevented the cyclic thrombotic process, and
      induced gradual thrombus dissolution. Ex vivo, at 1800 s(-1), collagen exposure
      to untreated blood for 2 minutes, 4 minutes, or two consecutive periods of 2
      minutes each resulted in similar platelet adhesion, 56%, 59%, and 61%,
      respectively, with an average thrombus volume of 6, 19, and 17.5 microm3/microm2,
      respectively, without any fibrin formation. This indicated that the two
      consecutive perfusions did not affect the dynamic process of thrombus growth.
      When collagen-adherent platelets deposited after the first 2-minute perfusion
      were perfused for 2 minutes with VCL-, ATA-, or lamifiban-treated blood, thrombus
      growth was prevented and platelet adhesion remained unchanged, but fibrin
      formation increased on and around the predeposited platelets. These results
      suggest that both the GPIb/IX-vWF axis and GPIIb/IIIa are involved in in vivo
      platelet-to-platelet interactions at high shear rates in the guinea pig.

PMID- 9157957
TI  - Structural aspects of heparin responsible for interactions with von Willebrand
      factor.
AB  - Unfractionated heparin (UFH) binds von Willebrand factor (vWF) and inhibits the
      vWF-platelet GP Ib interaction. For vWF, a heparin-binding domain has been
      identified, but for heparin, the structures that confer such activity are
      unknown. To investigate this, UFH was depolymerized by methods that yield
      structurally distinct fragments. The glycosaminoglycans (GAGs) produced were
      separated into five groups of homogeneous molecular weight (MW). Anti-Xa
      activity, vWF binding affinity, and vWF-dependent platelet agglutination were
      measured. Periodate oxidation but not heparinase digestion destroyed anti-Xa
      activity. At all MWs, periodate conferred greater vWF binding affinity and
      greater ability to inhibit platelet agglutination than heparinase. As an example,
      at MW 6100, the binding IC50 was 100+/-19 micromol/L for a periodate-derived GAG
      and 527+/-70 micromol/L for a heparinase-derived GAG. At the same MW, the
      agglutination IC50 was 17+/-5 micromol/L for periodate and 135+/-18 micromol/L
      for heparinase. This suggests that the disaccharide GlcNS[6S]-IdoA2S, destroyed
      by heparinase but not periodate, is crucial to heparin-vWF interactions. An MW
      dependency was also noted, with a minimum dodecasaccharide required for activity
      inhibition. To further investigate the heparin/vWF interaction, affinity
      fractionation of heparins was performed with an immobilized peptide derived from
      a heparin-binding domain of vWF. Disaccharide analysis of high-affinity heparins
      revealed an increased ratio of IdoA2S-GlcN[S/Ac]6S to IdoA2S-GlcN[S/Ac]. Affinity
      fractionation of oligosaccharides (MW 3500) diminished the relative content of
      all disaccharides except IdoA2S-GlcNS6S, which was increased. These data suggest
      that the disaccharide structures IdoA2S-GlcNS6S and GlcNS6S-IdoA2S are crucial to
      heparin/vWF interactions. Understanding the structural aspects that confer such
      activity may be useful in designing heparin-based antithrombotic drugs.

PMID- 9157958
TI  - Inhibition of proliferation and stimulation of migration of endothelial cells by
      secretoneurin in vitro.
AB  - Vascular cell responses in inflammation are affected by several neuropeptides of
      perivascular nerve fibers. Secretoneurin is a 33-amino acid peptide that is
      coreleased from these nerve endings with other proinflammatory neuropeptides, eg,
      substance P and calcitonin gene-related peptide. Furthermore, secretoneurin has
      been shown to be chemotactic for human skin fibroblasts and human blood monocytes
      in vitro and in vivo. An action on cellular components of the vascular wall is
      not yet reported. We therefore investigated in vitro effects of this novel
      sensory neuropeptide on endothelial cells. Secretoneurin exerted a potent and
      reversible inhibitory effect both on endothelial cell growth under low serum
      conditions (1% fetal calf serum) and endothelial cell growth factor-activated
      endothelial cell proliferation. We show in the present study that secretoneurin
      exerts this effect on aortic (rat) and pulmonary artery (bovine) endothelial
      cells, as well as venous (human umbilical vein) endothelium. Endothelial cell
      chemotaxis was tested by means of three different migration assays employing
      nitrocellulose and polycarbonate micropore filters. Secretoneurin consistently
      exhibited potent chemoattractant activity. The effective concentrations for the
      observed effects were in the picomolar range. The combination of chemotactic and
      antiproliferative effects on endothelial cells suggests that secretoneurin may
      act as a regulatory factor of vascular cell functions.

PMID- 9157959
TI  - Acidic and basic fibroblast growth factors suppress transcriptional activation of
      tissue factor and other inflammatory genes in endothelial cells.
AB  - Tissue factor (TF) is a transmembrane receptor that serves as a cofactor for
      factor VIIa and initiates the extrinsic pathway of blood coagulation. Under
      normal physiological conditions, TF is expressed in extravascular and
      perivascular cells but not in vascular endothelial cells and monocytes. TF can be
      induced in these cells by inflammatory regulators and other stimulators, such as
      LPS, thrombin, oxidized lipoproteins, and certain growth factors. An earlier
      study showed that growing primary cultures of human umbilical vein endothelial
      cells (HUVECs) with endothelial cell growth supplement (ECGS) and heparin had
      impaired the ability of monolayers to express surface membrane TF activity after
      perturbation. The mechanism by which ECGS suppressed TF activity was not known.
      In the present study, we investigated the effect of recombinant acidic and basic
      fibroblast growth factors (aFGF and bFGF) on the induction of TF in a HUVEC cell
      line and a fibroblast cell line. Both aFGF and bFGF suppressed the phorbol
      myristate acetate-induced expression of TF in endothelial cells but not the serum
      induced expression of TF in fibroblast cells. Diminished expression of the cell
      surface TF activity observed in endothelial cells grown with aFGF or bFGF was due
      to the accumulation of a lower number of TF mRNA transcripts. TF mRNA stability
      was not altered in HUVECs grown with aFGF or bFGF. Nuclear run-on experiments
      revealed that the transcription of TF and several other genes that play an
      important role in inflammation and angiogenesis was reduced in the endothelial
      cells that were cultured with aFGF or bFGF. The diminished expression of TF may
      be part of a generalized response of endothelial cells to FGF that facilitates
      migration of endothelial cells during angiogenesis.

PMID- 9157960
TI  - Cellular radiosensitivity, radioresistant DNA synthesis, and defect in
      radioinduction of p53 in fibroblasts from atherosclerosis patients.
AB  - Earlier studies have suggested that both cancer and atherosclerosis may follow a
      common pathway in the early stage of development and share certain risk factors.
      One report indicated that the gene responsible for the radiosensitive, cancer
      prone, multisystem disorder ataxia telangiectasia (AT) may increase the risk of
      developing ischemic heart disease. The present studies were carried out to find
      similarities, if any, between atherosclerosis patients and AT homozygotes or
      heterozygotes (ATHs) in their cellular/molecular response to ionizing radiation,
      which acts as a carcinogen as well as an atherogen. Fibroblast cell strains
      developed from healthy subjects and from AT homozygotes, ATHs, and
      atherosclerosis patients were compared for (1) survival, by the colony-forming
      assay and (2) DNA synthesis inhibition after irradiation, determined by
      [3H]thymidine incorporation, cell cycle distribution, and the expression of p53
      and p21 proteins, analyzed by flow cytometry. Fibroblasts from the
      atherosclerosis patients as a group, compared with the healthy subjects, showed
      enhanced sensitivity to chronic (low-dose-rate) irradiation. A majority of the
      cell strains representing atherosclerosis patients exhibited varying degrees of
      radioresistant DNA synthesis (RDS), with roughly 33% showing an AT-like and the
      rest an ATH-like response. All cell strains with an AT-like and one quarter with
      an ATH-like RDS were found to be defective in the radioinduction of both p53 and
      p21 proteins, which are concerned with cell cycle regulation. An absence of G1
      arrest after irradiation was observed in cell strains lacking a radioinduced
      expression of p53 and p21. Cellular/molecular defects leading to increased
      radiosensitivity, reduced induction of p53/p21, and cell cycle deregulation found
      to be associated with cancer-prone disorders such as AT may constitute important
      risk factors for atherosclerosis as well.

PMID- 9157961
TI  - Expression of the PAF receptor in human monocyte-derived macrophages is
      downregulated by oxidized LDL: relevance to the inflammatory phase of
      atherogenesis.
AB  - Human monocyte-derived macrophages play a major role in the initiation and
      progression of atherosclerotic lesions as a result of the production of a wide
      spectrum of proinflammatory and prothrombotic factors. Among such factors is a
      potent inflammatory phospholipid, platelet-activating factor (PAF), which is
      produced after macrophage activation. Because the cells involved in PAF
      biosynthesis are typically targets for the bioactions of PAF via specific cell
      surface receptors, we evaluated the expression of the PAF receptor in human
      monocyte-derived macrophages. Oxidized LDL (oxLDL) exerts multiple cellular
      effects that enhance lesion progression; we therefore investigated the potential
      modulation of expression of the macrophage PAF receptor by oxLDL. [3H]PAF bound
      to adherent human macrophages with a K(d) of 2.1 nmol/L and a B(max) of 19
      fmol/10(6) cells; approximately 5300 binding sites per cell were detected. OxLDL
      (100 microg protein per milliliter) induced a twofold decrease in cellular PAF
      binding after 3 hours at 37 degrees C. Analysis of macrophage mRNA by reverse
      transcription-polymerase chain reaction (RT-PCR) revealed two forms corresponding
      to the PAF receptor, of which the leukocyte type (type 1 promoter) predominated.
      Expression of PAF receptor mRNA, evaluated by quantitative RT-PCR using an actin
      or a GAPDH mimic, was progressively reduced (up to 70%) by oxLDL up to 6 hours
      and remained low for at least 24 hours. Such downregulation was reversible after
      incubation of the cells for 24 hours in oxLDL-free medium. Addition of forskolin
      (3 micromol/L) or dibutyryl cAMP (1 mmol/L) to macrophage cultures reproduced the
      oxLDL-mediated inhibition of PAF receptor expression; carbamyl PAF reduced PAF
      binding and PAF mRNA to a similar degree (approximately 50%). These data
      demonstrate that atherogenic oxLDL downregulates the expression of both cellular
      PAF receptors and PAF receptor mRNA in macrophages, consistent with both a
      diminished bioresponse to PAF and decreased cell motility. Such diminished
      bioresponse to a powerful antacoid reflects the suppression of an acute
      inflammatory reaction, thereby leading to chronic, low-level inflammation, such
      as that characteristic of fatty streaks and more advanced atherosclerotic
      plaques.

PMID- 9157962
TI  - Platelet-activating factor and oxidized LDL induce immune activation by a common
      mechanism.
AB  - Platelet activating factor (PAF) is a phospholipid with proinflammatory and
      thrombogenic properties, which has been implicated in inflammatory disorders
      including vasculitis and asthma. PAF-like compounds are present in oxidized LDL
      (oxLDL), which has been detected in the atherosclerotic lesion, where it may
      activate monocytes, macrophages, and T cells. OxLDL may therefore both initiate
      and perpetuate inflammatory reactions in the artery wall. Herein we demonstrate
      that PAF has the capacity to induce enhanced interferon gamma (IFN-gamma)
      secretion in peripheral blood mononuclear leukocytes (PBMCs), as does oxLDL. Both
      oxLDL- and PAF-induced IFN-gamma secretions were inhibited by a specific PAF
      receptor antagonist, WEB 2170. PAF-like lipids in oxLDL could thus be responsible
      for oxLDL-induced activation of immune-competent cells. The effects of PAF and
      oxLDL were inhibited by antibodies to major histocompatibility complex class II
      and thus depend on accessory cells like monocytes. Both PAF and oxLDL induced
      tumor necrosis factor-alpha (TNF-alpha) synthesis in peripheral blood. PAF
      mediated TNF-alpha production was inhibited by WEB 2170, whereas oxLDL-induced
      TNF-alpha was only partially inhibited. These findings indicate that both PAF and
      oxLDL have the capacity to induce TNF-alpha, which may increase atherogenesis due
      to its pleiotropic proinflammatory effects. Our findings suggest that the PAF
      receptor plays an important role in the inflammatory component of
      atherosclerosis.

PMID- 9157963
TI  - Regulation of scavenger receptor expression in smooth muscle cells by protein
      kinase C: a role for oxidative stress.
AB  - Phorbol esters increase scavenger-receptor mRNA expression and receptor activity
      in smooth muscle cells (SMCs). Our present results demonstrate that activation of
      protein kinase C (PKC) mediates this increase in receptor expression. This
      conclusion is based on the findings that (1) phorbol esters induced translocation
      of PKC-alpha from the cytosol to the membrane fraction; (2) PKC inhibitors
      blocked the effect of phorbol esters on receptor expression; (3) diacylglycerol,
      a physiological PKC agonist, enhanced scavenger-receptor activity; and (4) in
      cotransfected human SMCs, constitutively active PKC-alpha stimulated the
      expression of a reporter gene under control of the scavenger-receptor promoter.
      Phorbol ester treatment of SMCs increased intracellular reactive oxygen, and the
      increase in receptor activity was reduced 30% by the antioxidant N-acetyl
      cysteine (NAC), suggesting a role for reactive oxygen in phorbol ester-mediated
      receptor regulation. Furthermore, direct treatment of SMCs with reactive oxygen
      species increased scavenger-receptor activity. In rabbit SMCs, 100 micromol/L
      H2O2 alone slightly increased scavenger-receptor mRNA and protein expression. In
      combination, 100 micromol/L H2O2 and 10 micromol/L vanadate, which promotes
      formation of OH and enhances the inhibition of protein tyrosine phosphatase by
      H2O2, increased scavenger-receptor mRNA expression 25-fold in rabbit SMCs and 8
      fold in human SMCs. NAC reduced the effect of H2O2 and vanadate by 93%. The
      increase in SMC scavenger-receptor expression occurs at the level of gene
      transcription. Receptor mRNA half-life was unchanged after treatment with either
      phorbol esters or reactive oxygen (approximately 14.5 hours), and induction by
      phorbol esters increased SMC scavenger-receptor mRNA transcription, as determined
      by nuclear run-on assay. Multiple cytokines and growth factors that contribute to
      the generation of reactive oxygen species are present in atherosclerotic lesions.
      These factors may all contribute to the upregulation of SMC scavenger-receptor
      activity and therefore to the formation of smooth muscle foam cells.

PMID- 9157964
TI  - Impact of a combination of a calcium antagonist and a beta-blocker on cell- and
      copper-mediated oxidation of LDL and on the accumulation and efflux of
      cholesterol in human macrophages and murine J774 cells.
AB  - Calcium antagonists and beta-blockers may retard or inhibit atherogenesis. In the
      absence of data pertaining to the potential cardioprotective action of an
      association of such agents, we have investigated the impact of nifedipine and
      atenolol, alone or in combination, on the capacity of monocyte-macrophages (ex
      vivo) and copper ions (in vitro) to oxidize LDL and on intracellular metabolism
      and efflux of free and esterified forms of cholesterol in human macrophages and
      foam cells. At concentrations up to 100 micromol/L, atenolol had no effect on the
      oxidative resistance of LDL; on the contrary, nifedipine displayed a significant
      dose-dependent capacity to protect LDL during copper-mediated oxidation (100
      micromol/L; P<.001). Using a DPPH radical generating system, nifedipine was shown
      to exert free radical-trapping activity (molar ratio of scavenging activity,
      nifedipine:alpha-tocopherol, 1:114). The addition of atenolol to nifedipine was
      without effect on the antioxidant activity of the calcium antagonist. In
      experiments in which oxidative modification was mediated by monocyte-macrophages,
      nifedipine but not atenolol conserved its antioxidant capacity. Furthermore, we
      demonstrated that association of atenolol with nifedipine did not modify the
      antioxidant properties of nifedipine itself. Using a human monocyte-derived
      macrophage culture system, nifedipine, atenolol, or a combination of the two
      drugs was ineffective in inhibiting foam cell formation induced by acetylated LDL
      or oxidized LDL. However, atenolol (100 micromol/L) increased cellular
      accumulation of cholesteryl ester (+17%; P<.05), whereas nifedipine (100
      micromol/L) decreased total cholesterol (-37.4%; P<.05) accumulation induced by
      acetylated LDL in the mouse macrophage cell line J774. A combination of the two
      drugs neutralized these antagonistic effects. None of these results were
      reproduced during the oxidized LDL-induced transformation of murine J774 cells
      into foam cells. Furthermore, cholesterol efflux from preloaded human macrophages
      was equally unaffected by the addition of the drugs alone or in combination. It
      therefore seems unlikely that the beneficial effect of atenolol on coronary heart
      disease is mediated by changes in either LDL oxidizability or cholesterol
      metabolism in human macrophages and foam cells. Our findings with nifedipine
      suggest, however, that this calcium antagonist may potentially exert
      antiatherosclerotic properties via a reduction of the oxidative modification of
      LDL, thereby affecting a reduction in foam cell formation and in the
      pathophysiological cellular activities of oxidized lipids, rather than by
      inducing a direct reduction in cholesterol accumulation in human foam cells of
      macrophage origin.

PMID- 9157965
TI  - Plasma total homocysteine, B vitamins, and risk of coronary atherosclerosis.
AB  - Epidemiological research has shown that elevated plasma total homocysteine (tHcy)
      is a risk factor for atherosclerotic disease. In the present case-control study,
      we investigated whether fasting or postmethionine-loading tHcy was a stronger
      predictor of risk of severe coronary atherosclerosis. Furthermore, we studied
      levels of B vitamins, which are involved in homocysteine metabolism. Subjects
      were recruited from men and women, aged 25 to 65 years, who underwent coronary
      angiography between June 1992 and June 1994 in a hospital in Rotterdam, The
      Netherlands. Cases (n=131) were defined as those with > or =90% occlusion in one
      and > or =40% occlusion in a second coronary artery, while control subjects
      (n=88) had <50% occlusion in only one coronary vessel. In addition, a population
      based control group free from clinical cardiovascular disease (n=101) was
      studied. Coronary patients were studied at least 2.5 months after angiography or
      other acute illness, such as myocardial infarction. After adjusting for age and
      sex differences between the groups, cases had 9% (P=.01) higher geometric mean
      fasting and 7% (P=.04) higher geometric mean postload tHcy than the combined
      control groups. Despite higher levels of tHcy for cases, their geometric mean
      levels of red cell folate and pyridoxal 5'-phosphate were higher than for control
      subjects, whereas plasma vitamin B12 was only slightly lower in cases. The
      frequency distribution of tHcy values in cases was slightly shifted toward the
      right, across the entire range, compared with the distribution in the combined
      control group. This was somewhat more obvious for fasting than postload tHcy
      levels. The odds ratio (OR) for severe coronary atherosclerosis (case status) for
      each 1 SD increase in fasting tHcy (5 micromol/L) was 1.3 (95% confidence
      interval [CI], 1.0-1.6), similar to the OR for each 1 SD increase (12 micromol/L)
      in postmethionine-loading tHcy (1.3 [95 CI, 1.0-1.7]), after adjustment for sex,
      age, and other potential confounders. Furthermore, there was a significant linear
      trend of increasing fasting tHcy with increasing number of occluded arteries
      (P=.01), correcting for sex, age, and other potential confounders. Our data show
      a positive association between plasma tHcy and risk of severe coronary
      atherosclerosis, of similar strength for fasting and postload tHcy levels. The
      data suggest that the association exists over a wide range of tHcy levels,
      without a clear cutoff point below which there is no increased risk.

PMID- 9157966
TI  - A novel mosaic protein containing LDL receptor elements is highly conserved in
      humans and chickens.
AB  - Certain receptors belonging to the LDL receptor (LDLR) gene family appear to
      constitute a newly identified branch whose members are expressed in brain, in
      addition to other tissues. In support of this concept, we have now discovered the
      expression and delineated the molecular structures of a representative of this
      emerging branch from two such diverse species as human and chicken. This membrane
      receptor, called LR11 and thus far only known to exist in the rabbit, is a
      complex seven-domain mosaic protein containing, among other structural elements,
      a cluster of 11 LDLR ligand-binding repeats and a domain with homology to VPS10,
      a yeast receptor for vacuolar protein sorting. Cytoplasmic signature sequences
      define the receptor as competent for endocytosis. The most striking properties of
      LR11s are their (1) high degree of structural conservation (>80% identity among
      mammals and birds), with 100% identity in the membrane-spanning and cytoplasmic
      domains of rabbit and human; (2) lack of regulation by cholesterol and estrogen;
      and (3) expression in brain. The features of LR11 suggest important roles in
      intercellular and intracellular ligand transport processes, some of which it may
      share with other brain-specific LDLR family members.

PMID- 9157967
TI  - Differentiation, dedifferentiation, and apoptosis of smooth muscle cells during
      the development of the human ductus arteriosus.
AB  - Differentiation of vascular smooth muscle cells (SMCs) is characterized by
      several molecular transitions. As differentiation proceeds, proteins of the
      cytoskeletal and contractile apparatus, such as alpha-smooth muscle actin, smooth
      muscle myosin, calponin, and heavy caldesmon, and the expression of the membrane
      related protein smooth muscle phosphoglucomutase-related protein increase,
      whereas the expression of other proteins, such as fibronectin splice variants
      with extradomains A (EDA) and B (EDB), decreases. In this study, we investigated
      the differentiation of the SMCs of the ductus arteriosus during the development
      of intimal thickening. Ascending and descending aortas of the same age were used
      for comparison because these vessels lack intimal thickening. In the fetal ductus
      arteriosus, a relatively early differentiation of the contractile apparatus was
      observed compared with the ascending and descending aortas. EDA and EDB
      expression was already low, being similar in the ductus and descending aorta and
      even lower in the ascending aorta. In the neonatal ductus, SMCs of the media and
      outer intima were well differentiated and comparable with SMCs of the ascending
      aorta. Dedifferentiated SMCs, with a low expression of cytoskeletal and
      contractile proteins and a high expression of EDA and EDB, were found in regions
      in the inner intima that show features of progression of intimal thickening and
      in areas of cytolytic necrosis in the media. With a technique using in situ end
      labeling of DNA fragments, we found extensive apoptosis in the area of cytolytic
      necrosis and to a lesser extent in these areas of the inner intima. In
      conclusion, SMCs of the fetal ductus arteriosus have an advanced differentiation
      of the contractile apparatus compared with the adjacent aorta. Reexpression of
      fetal characteristics is seen in a number of cells in inner intima and media of
      the neonatal ductus arteriosus. The finding of apoptosis in these areas suggests
      that dedifferentiation and apoptosis are associated processes that may play a
      role in vascular remodeling.

PMID- 9157968
TI  - Nitrotyrosine formation, apoptosis, and oxidative damage: relationships to nitric
      oxide production in SJL mice bearing the RcsX tumor.
AB  - In SJL mice, growth of RcsX lymphoma cells results in activation of macrophages
      in the spleen and lymph nodes to produce high levels of NO radical (NO.). We used
      this experimental model system to study the toxicology of NO. in vivo. To
      characterize spatial relationships between sites of NO. production and tissue
      damage, immunohistochemical techniques were developed for simultaneous detection
      of inducible NO. synthase (iNOS), 3-nitrotyrosine, and apoptosis in spleen and
      lymph nodes of tumor-bearing animals. Elevated expression of iNOS, presumed to
      reflect increased NO. production, was associated with a significant increase in
      frequency of apoptotic nuclei. Both apoptotic nuclei and 3-nitrotyrosine staining
      were found in cells juxtaposed to iNOS-expressing (ie., NO.-producing)
      macrophages and also within the macrophages themselves. To assess the extent of
      DNA damage associated with the response, 8-oxoguanine levels were quantified in
      DNA extracted from spleens of tumor-bearing mice. No increase in levels of this
      marker of oxidative DNA damage was found in tissues in which apoptosis and 3
      nitrotyrosine levels were highly elevated within specific subsets of cells.
      Collectively, our results indicate that under the pathophysiological conditions
      existing in the RcsX tumor-bearing SJL mouse, cellular damage caused by NO.
      and/or other reactive species produced by activated macrophages is highly
      localized within cells in close proximity to the activated macrophages.

PMID- 9157969
TI  - Combretastatin A-4, an agent that displays potent and selective toxicity toward
      tumor vasculature.
AB  - Selective induction of vascular damage within tumors represents an emerging
      approach to cancer treatment. Histological studies have shown that several
      tubulin-binding agents can induce vascular damage within tumors but only at doses
      approximating the maximum tolerated dose, which has limited their clinical
      applicability. In this study, we show that the combretastatin A-4 prodrug induces
      vascular shutdown within tumors at doses less than one-tenth of the maximum
      tolerated dose. In vitro studies indicate that a short drug exposure results in
      profound long-term antiproliferative/cytotoxic effects against proliferating
      endothelial cells but not cells that are quiescent prior to and during drug
      exposure. Vascular shutdown, within experimental and human breast cancer models
      in vivo following systemic drug administration, was demonstrated with a reduction
      in functional vascular volume of 93% at 6 h following drug administration and
      persisted over the next 12 h, with corresponding histology consistent with
      hemorrhagic necrosis resulting from vascular damage. These actions against tumor
      vasculature and the broad therapeutic window demonstrate the clinical potential
      of these drugs and warrant further study to elucidate the mechanisms responsible
      for the antivascular effects of combretastatin A-4.

PMID- 9157970
TI  - Intracellular ATP levels determine cell death fate by apoptosis or necrosis.
AB  - Although apoptosis and necrosis are morphologically distinct manifestations of
      cell death, apoptosis and some necroses share common features in the death
      signaling pathway involving functional steps of death-driving interleukin 1beta
      converting enzyme family proteases and anti-cell death protein Bcl-2. One evident
      physiological difference in cells undergoing apoptosis versus necrosis is in
      intracellular levels of ATP. In this study, we specifically addressed the
      question of whether apoptosis depends on intracellular ATP levels, since longer
      incubation under ATP-depleting conditions results in necrotic cell death.
      Incubation of cells in glucose-free medium with an inhibitor of mitochondrial
      F0F1-ATPases reduces intracellular ATP levels and completely blocks Fas/Apo-1
      stimulated apoptosis. ATP supplied through glycolysis or oxidative
      phosphorylation restores the apoptotic cell death pathway. ATP depletion also
      leads to a block in Fas-induced activation of CPP32/Yama(-like) proteases, and
      when ATP is depleted after the activation of the proteases, subsequent apoptosis
      is significantly blocked. Thus, ATP-dependent steps exist both upstream and
      downstream of CPP32/Yama(-like) protease activation in apoptotic signal
      transduction. Treatment with the calcium ionophore induces apoptosis under ATP
      supplying conditions but induces necrotic cell death under ATP-depleting
      conditions, indicating that ATP levels are a determinant of manifestation of cell
      death.

PMID- 9157971
TI  - In vitro and in vivo resistance to cisplatin in cells that have lost DNA mismatch
      repair.
AB  - In vitro studies have shown that loss of DNA mismatch repair due to lack of
      either hMSH2 or hMLH1 activity results in low-level resistance to cisplatin but
      not to oxaliplatin, an analogue that produces a different type of DNA adduct. No
      information is currently available on whether this low-level resistance is
      sufficient to result in enrichment of mismatch repair-deficient cells during drug
      exposure in vitro or to account for clinical failure of treatment in vivo. Mixed
      populations of cells containing a minority of DNA mismatch repair-deficient cells
      constitutively expressing green fluorescence protein were exposed repeatedly in
      vitro to cisplatin and oxaliplatin. Treatment with cisplatin resulted in a
      gradual enrichment for DNA mismatch repair-deficient cells, whereas treatment
      with oxaliplatin did not. MSH2-/- and MSH2+/+ embryonic stem cells were
      established as xenografts in athymic nude mice. Animals were treated 48 h after
      tumor implantation with a single LD10 dose of either cisplatin or oxaliplatin.
      MSH2-/- tumors were significantly less responsive to cisplatin than MSH2+/+
      tumors, whereas there was no difference in sensitivity to oxaliplatin. These
      results demonstrate that the degree of cisplatin resistance conferred by loss of
      DNA mismatch repair is sufficient to produce both enrichment of mismatch repair
      deficient cells during treatment in vitro and a large difference in clinical
      responsiveness in vivo. The results identify loss of DNA mismatch repair as a
      mechanism of resistance to cisplatin but not oxaliplatin.

PMID- 9157972
TI  - GGTI-298 induces G0-G1 block and apoptosis whereas FTI-277 causes G2-M enrichment
      in A549 cells.
AB  - The mechanism by which the geranylgeranyltransferase I inhibitor GGTI-298 and the
      farnesyltransferase inhibitor FTI-277 inhibit human tumor growth is not known.
      Herein, we demonstrate that in the human lung adenocarcinoma A549 cells, GGTI-298
      induced a G1-G0 block whereas FTI-277 induced an enrichment in the G2-M phase of
      the cell cycle. Although FTI-277, GGTI-298, and compactin inhibited A549 cell
      growth, only GGTI-298 and compactin induced apoptosis as demonstrated by four
      criteria: 4',6-diamidine-2-phenylindoledihydrochloride staining, terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling, DNA fragmentation
      assay, and flow cytometry. Furthermore, the involvement of geranylgeranylated
      proteins in apoptotic pathways was confirmed by demonstrating that
      geranylgeraniol was able to block the ability of compactin to induce apoptosis.
      These results suggest that protein geranylgeranylation is critical for the
      control of programmed cell death and that, in A549 cells, farnesylated and
      geranylgeranylated proteins are involved in G2-M and G0-G1, respectively.

PMID- 9157973
TI  - The insulin-like growth factor II receptor gene is mutated in genetically
      unstable cancers of the endometrium, stomach, and colorectum.
AB  - Disruption of the DNA mismatch repair system, characterized by microsatellite
      instability (MI), plays an important role in the course of human carcinogenesis.
      Repetitive sequences constitute targets for mutation in MI+ cells, and frequent
      mutations have indeed been reported in such regions within the transforming
      growth factor beta receptor II (RII) gene in genetically unstable colorectal and
      gastric cancers. However, other genes that are targets for mutations in MI+ cells
      during the course of carcinogenesis have proven elusive. Because the insulin-like
      growth factor II receptor (IGFIIR) gene contains several repetitive sequences
      within its coding region, we examined mutations of this gene in MI+ cancers
      occurring at various primary sites. We found frameshift mutations in the poly(G)8
      tract of IGFIIR in eight tumors, all of which were MI+: 4 of 26 (15%) MI+
      endometrial cancers, 3 of 12 (25%) MI+ gastric cancers, and 1 of 18 (6%) MI+
      colorectal cancers. In contrast, no mutation was found in 51 pancreatic cancers,
      7 of which (14%) were MI+. These results implicate abnormal IGFIIR-mediated
      growth control in carcinogenesis involving the endometrium, stomach, and
      colorectum but not the pancreas.

PMID- 9157974
TI  - Localization of the multiple endocrine neoplasia type I (MEN1) gene based on
      tumor loss of heterozygosity analysis.
AB  - Multiple endocrine neoplasia type I (MEN1) is an inherited syndrome that results
      in parathyroid, anterior pituitary, and pancreatic and duodenal endocrine tumors
      as well as foregut carcinoids in affected patients. The gene responsible for the
      disease has been linked to chromosome 11q13. We analyzed loss of heterozygosity
      (LOH) in 188 tumors from 81 patients in an attempt to further define the location
      of the MEN1 gene. Both tumors from MEN1 patients and corresponding sporadic
      tumors were analyzed. Tumor types included parathyroid, gastrinoma, pancreatic
      endocrine, pituitary, and lung carcinoid. Six tumors (three MEN1 and three
      sporadic tumors) were identified that provided important LOH boundaries. Four
      tumors (two parathyroid tumors, one gastrinoma, and one lung carcinoid tumor)
      showed allelic loss that placed the MEN1 gene distal to marker PYGM. Two tumors
      (one gastrinoma and one parathyroid tumor) showed an LOH boundary that placed the
      gene proximal to D11S449, one of which further moved the telomeric boundary to
      D11S4936. Taken together, the present data suggest that the MEN1 gene lies
      between PYGM and D11S4936, a region of approximately 300 kb on chromosome 11q13.

PMID- 9157976
TI  - Application of telomerase assay for the screening of cervical lesions.
AB  - Telomerase is a ribonucleoprotein that synthesizes telomeric DNA onto chromosomal
      ends. The expression of telomerase is thought to be required for cellular
      immortality and oncogenesis. Telomerase activity has been detected not only in
      most cancers but also in some types of premalignant lesions, such as squamous
      intraepithelial lesions (SILs). In the present study, we used the telomerase
      assay to detect uterine cervical lesions in cervical scraping samples. A total of
      82 cervical scraping samples were obtained from women with or without cervical
      lesions and examined by nonradioisotope telomeric repeat amplification protocol
      assay. Fifteen of 17 (88%) cervical cancer specimens exhibited telomerase
      activity, whereas 5 of 8 (63%) and 14 of 24 (58%) specimens from low-grade and
      high-grade SILs, respectively, also exhibited telomerase activity. In contrast, 3
      of 33 (9%) specimens from normal cervices exhibited telomerase activity. Dilution
      telomeric repeat amplification protocol assay was performed to estimate
      telomerase activity; it revealed that high levels of activity were often
      expressed in cervical cancer. Cytological examination was also performed by Pap
      smear test, and 4 of 8 (50%) low-grade SILs, 21 of 24 (88%) high-grade SILs, and
      16 of 17 (94%) cervical cancers were found to have cytological abnormalities.
      There were discordances in some cases between findings of smear abnormality and
      telomerase positivity. In particular, we found five cases of SILs without smear
      abnormality but with telomerase activity, suggesting that some lesions with false
      negative cytology can be detected by telomerase assay. These findings suggest
      that telomerase assay using cervical scrapings might be a useful screening method
      for cervical lesions especially when combined with a Pap smear test.

PMID- 9157975
TI  - Evidence for genetic heterogeneity in familial Wilms' tumor.
AB  - Wilms' tumor (WT), a childhood kidney cancer, occurs both sporadically and, less
      frequently, in a familial context. Genetic linkage studies of several large WT
      families have excluded the one cloned WT gene, WT1, as the locus responsible for
      familial predisposition. These data demonstrate the existence of a familial
      predisposition gene distinct from WT1 and, more broadly, imply that the genetic
      etiology of WT is heterogenous. However, it has been unknown whether the
      predisposition observed in large WT families is also heterogenous or perhaps is
      due to mutations at a single locus. Recently, examination of a large French
      Canadian WT family has demonstrated genetic linkage to 17q12-q21. We report here
      the results from a genetic linkage study of six WT pedigrees. Analyses of
      genotype data from eight loci within the 17q12-q21 region in these families
      resulted in cumulative lod scores of <-4.0 through the region, thereby excluding
      linkage. The ability to rule out the 17q region as the site of a predisposition
      gene in several of these pedigrees individually demonstrates the existence of
      more than one gene that predisposes to WT in large pedigrees and again emphasizes
      that the etiology of WT is genetically heterogenous.

PMID- 9157977
TI  - Adenovirus-mediated expression of PML suppresses growth and tumorigenicity of
      prostate cancer cells.
AB  - Our previous studies demonstrated that the promyelocytic leukemia gene, PML,
      encodes a growth and transformation suppressor. Overexpression of PML inhibits
      cancer cell growth in vitro and in vivo. In this study, we further explored the
      possibility of applying PML as a potential agent for developing prostate cancer
      gene therapy using an adenovirus delivery system. We have constructed and
      produced the recombinant PML-adenovirus, Ad-PML, in which the full-length PML
      cDNA is driven by the strong cytomegalovirus promoter. In LNCaP, DU145, and PC-3
      prostate cancer cell lines, an infection efficiency of 90% can be achieved at a
      concentration of 2, 10, and 100 multiplicity of infection (MOI), respectively.
      Western blotting and immunofluorescence staining demonstrated that the AD-PML
      infected cells expressed a high level of PML protein. The protein expression
      peaked at days 3-4 postinfection, and a detectable level of PML was found at day
      18 after viral infection. To test the effect of Ad-PML on the growth of prostate
      cancer cells, the DU145 and LNCaP cells were infected with 10 and 2 MOI of Ad
      PML. We found that the growth rate of the Ad-PML-infected DU145 and LNCaP cells
      were significantly inhibited. A tumorigenicity test in nude mice showed that the
      Ad-PML-treated DU145 cells failed to form tumors. Most importantly, direct
      injection of Ad-PML into DU145-induced tumors was able to repress tumor growth in
      nude mice by 64%. Taken together, these data indicate that PML is a tumor growth
      suppressor in prostate cancer and that Ad-PML may be a potential candidate for
      human prostate cancer therapy.

PMID- 9157978
TI  - Adenovirus infection enhances killing of melanoma cells by a mitotoxin.
AB  - Toxins are effective in cell killing if internalized efficiently. Conjugation of
      the plant toxin saporin with basic fibroblast growth factor has increased tumor
      killing due to better internalization, but toxin uptake by cells has remained
      relatively inefficient. We show here that infection of melanoma cells with a
      replication-defective adenovirus enhances cell killing by the mitotoxin basic
      fibroblast growth factor-saporin more than 10-fold, thus allowing tumor cell
      killing in vivo at nontoxic concentrations. Adenovirus infection leads to
      increased apoptosis by the mitotoxin due to enhanced internalization of the
      ligand-receptor complex and release of the active toxin from the endosomes.

PMID- 9157979
TI  - Potent pseudosubstrate-based peptide inhibitors for p60(c-src) protein tyrosine
      kinase.
AB  - We recently reported the identification of GIYWHHY as an efficient and specific
      substrate for p60(c-src) protein tyrosine kinase (PTK) by screening a secondary
      random peptide library (Q. Lou et al., Bioorg. Med. Chem., 4: 677-682, 1996).
      Based on the primary structure of GIYWHHY, we designed and synthesized several
      pseudosubstrate-based peptide inhibitors. Some of these peptide inhibitors are
      highly potent and specific with IC50 in the low micromolar range. Because both
      YIYGSFK and GIYWHHY are efficient and specific substrates for p60(c-src) PTK,
      chimeric branched peptides based on these two sequences were synthesized. These
      branched peptides inhibit p60(c-src) PTK with high potency, indicating that the
      enzyme-active site of p60(c-src) PTK can accommodate more than a linear motif.
      This may explain why seemingly several peptides with very different linear
      structures can all be phosphorylated by this enzyme.

PMID- 9157980
TI  - Ganglioside GD1alpha functions in the adhesion of metastatic tumor cells to
      endothelial cells of the target tissue.
AB  - We studied the role of glycosphingolipids expressed on the cell surfaces of a
      metastatic tumor cell line. Glycosphingolipid compositions of the low-metastatic
      murine lymphosarcoma cell line RAW117-P and its sub-line, RAW117-H10, which shows
      higher metastatic potential for the liver than P cells, were compared. Both types
      of cells had LacCer, Gg3Cer, and Gg4Cer as the major neutral glycosphingolipids
      and GM1b and GD1alpha as the gangliosides. There are differences in
      glycosphingolipid contents, the neutral glycosphingolipid contents in the
      parental cells being 1.5-fold higher than that in the variant ones. In contrast,
      the level of GD1alpha in H10 cells was twice as much as that in the P cells;
      however, the expression of other gangliosides was down-regulated. On the basis of
      the results of glycosphingolipid analysis, we investigated the functional role of
      GD1alpha in H10 cells in the adhesion of the tumor cells to the target tissue by
      using hepatic sinusoidal endothelial (HSE) cells. GD1alpha and GM1b inhibited the
      adhesion when HSE cells were incubated prior to coculture with the tumor cells.
      This inhibitory effect by GD1alpha and GM1b was observed within 30 min after
      addition of H10 cells to HSE cells and was dose dependent. GD1alpha showed a
      higher inhibitory effect on the adhesion than GM1b, whereas other
      glycosphingolipids showed no inhibitory effect. Anti-GD1alpha monoclonal antibody
      also inhibited the adhesion between the H10 and HSE cells. When cultured without
      fetal bovine serum for 30 min in a various glycosphingolipids-coated dish for
      bacterial culture, HSE cells adhered to the area coated with GD1alpha but not to
      areas coated with other glycosphingolipids. HSE cell adhesion depended on the
      amount of GD1alpha coated on the plate. These data indicate that GD1alpha
      functions as an adhesion molecule in the process of metastasis of H10 cells.

PMID- 9157981
TI  - Characterization of early pulmonary hyperproliferation and tumor progression and
      their inhibition by black tea in a 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      induced lung tumorigenesis model with A/J mice.
AB  - The pathogenesis of pulmonary tumors induced by a tobacco carcinogen, 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and its inhibition by black
      tea have been characterized. Female A/J mice (6 weeks old) were treated with a
      single dose of NNK (103 mg/kg of body weight, i.p.) on day 0, and the cell
      proliferation index was measured by the incorporation of bromodeoxyuridine
      (BrdUrd) immunohistochemically. The number of BrdUrd-labeled cells increased in
      the bronchiolar epithelium from day 2 to day 14, with the highest proliferation
      rate observed on day 5. By day 35, the BrdUrd-labeling index returned to the
      level of the control group. Further examination of the day 35 samples revealed
      the presence of foci of hyperproliferative cells in the bronchiolar epithelium,
      particularly in the bronchiolalveolar regions. These proliferating bronchiolar
      epithelial cells (Clara cells) may be the initiated sites for pulmonary
      tumorigenesis. In this short-term model, administration of black tea polyphenols
      (0.3%) through the drinking water starting 24 h after NNK treatment significantly
      inhibited NNK-induced early bronchiolar cell proliferation on day 5. In long-term
      studies, adenomas were observed in 100% (15 of 15) of the mice at week 16, with
      7.8 +/- 0.8 tumors per mouse. At week 52, a malignant tumor incidence of 80% (41
      of 51 mice) and a malignant tumor multiplicity of 2.39 +/- 0.19 were observed.
      The growth patterns of the malignant tumors, which included solid, papillary, and
      mixed types, may be associated with the cellular origin of the tumor. The cell
      proliferation indices, as measured by proliferating cell nuclear antigen
      immunohistochemistry, were significantly higher in dysplasia within adenoma than
      in adenoma, and significantly higher in adenoma at week 52 than in adenoma at
      week 16. Administration of black tea, starting 16 weeks after a single dose of
      NNK, inhibited the progression of adenoma to adenocarcinoma as determined by both
      malignant tumor incidence and multiplicity. The cell proliferation rate in
      adenomas was also suppressed by black tea treatment. The present work
      demonstrates the antiproliferative activities of black tea and its polyphenols.
      Such activities, at the early and late stages of lung tumorigenesis, may be
      important for the cancer-chemopreventive activities of black tea.

PMID- 9157982
TI  - DNA damage-associated dysregulation of the cell cycle and apoptosis control in
      cells with germ-line p53 mutation.
AB  - Lymphoblastoid cell lines (LCLs) with heterozygous p53 mutations at residues
      286A, 133R, 282W, 132E, and 213ter were established from five independent Li
      Fraumeni syndrome families. When cell cycle regulation in response to gamma
      irradiation was studied, these LCLs showed an abnormal G1 checkpoint associated
      with defective inhibition of cyclin E/cyclin-dependent kinase 2 activity in all
      cases except for 282W LCL, which showed a normal G1 checkpoint. On the other
      hand, the control of S-phase-G2 as determined by cyclin A/cyclin-dependent kinase
      2 activity was defective in all these LCLs. The mitotic checkpoint was also
      defective in the two LCLs analyzed as either competent or incompetent for G1
      arrest. When radiation-induced apoptosis, which requires wild-type p53 function
      under optimal conditions, was studied, all of these LCLs showed significant
      failure compared to normal LCLs. These findings indicate that although p53
      dependent transactivation and G1-S-phase cell cycle control are variably
      dysregulated, the induction of apoptosis and control of the cell cycle at S-phase
      G2 and the mitotic checkpoint in response to DNA-damaging agents are consistently
      dysregulated in heterozygous mutant LCLs. This suggests that these dysfunctions
      underlie, at least in part, the susceptibility of Li-Fraumeni syndrome families
      to cancer. Furthermore, the approach presented is a potentially useful method for
      studying individual carriers of different germ-line p53 mutations and different
      biological features.

PMID- 9157983
TI  - Endometrial hyperplasia and apoptosis following neonatal diethylstilbestrol
      exposure and subsequent estrogen stimulation in both host and transplanted
      hamster uteri.
AB  - Prenatal exposure to the synthetic estrogen diethylstilbestrol (DES) causes
      morphogenetic alterations and neoplasia in the human reproductive tract. In the
      hamster, neonatal DES exposure alters early uterine morphogenesis and induces
      endometrial adenocarcinomas in adults. We now demonstrate that the preneoplastic
      stages of this phenomenon in the hamster reflect an abnormal uterotropic response
      to estrogen that is characterized by hyperplastic lesions in the endometrial
      epithelium and includes an immune and/or inflammatory component. Interestingly,
      biochemical and in situ analysis revealed that the hyperplastic epithelium is
      also an active site of cell death by apoptosis. To further probe the mechanism of
      this phenomenon, uteri from 7-day-old control or DES-exposed donors were
      transplanted into the cheek pouches of control or neonatally DES-exposed adult
      hosts, and both host groups were treated to provide high circulating levels of
      estradiol. Among the four ectopic scenarios, histopathological lesions
      (epithelial hyperplasia, dysplasia, and apoptosis), segregated almost exclusively
      to the two that consisted of neonatally DES-exposed uteri. The virtual absence of
      lesions in control uteri transplanted to DES hosts eliminated host systemic
      factors as causative agents. Therefore, we conclude that DES or its metabolites
      alter the cellular physiology and/or composition of the developing uterus
      (initiating event) in such a way that it thereafter responds abnormally to
      estrogenic stimulation (promoting event). These observations serve to further
      define a unique experimental system for probing: (a) various aspects of the
      clinical "DES Syndrome"; (b) how estrogen regulates normal uterine growth and
      morphogenesis; and (c) how this process can degenerate to the unregulated
      neoplastic state.

PMID- 9157984
TI  - Physiological melatonin inhibition of human breast cancer cell growth in vitro:
      evidence for a glutathione-mediated pathway.
AB  - Melatonin, the chief hormone secreted by the pineal gland, has been previously
      shown to inhibit human breast cancer cell growth at the physiological
      concentration of 1 nM in vitro. In this study, using the estrogen receptor (ER)
      positive human breast tumor cell line MCF-7, we have shown that 10 microM L
      buthionine-[S,R]-sulfoximine (L-BSO), an inhibitor of gamma-glutamylcysteine
      synthetase (the rate-limiting enzyme in glutathione synthesis), blocks the
      oncostatic action of 1 nM melatonin over a 5-day incubation, indicating that
      glutathione is required for melatonin action. The result was repeated with ZR75-1
      cells, suggesting that the glutathione requirement is a general phenomenon among
      ER+ breast cancer cells. Addition of exogenous glutathione (1 microM) to L-BSO
      treated groups restored the melatonin response in both cell lines. Further
      demonstration of the importance of glutathione was shown using the ER- breast
      tumor cell line HS578T, which is normally unresponsive to melatonin. Growth in
      this cell line was inhibited in the presence of 1 microM ethacrynic acid (an
      inhibitor of glutathione S-transferase) plus 1 nM melatonin, and this effect was
      blocked with 10 microM L-BSO. We also observed a steady decrease of intracellular
      glutathione in MCF-7 cells over a 5-day incubation, suggesting that these cells
      metabolize glutathione differently than do normal cells.

PMID- 9157985
TI  - Enhanced therapeutic effects of liposome-associated 1-O-octadecyl-2-O-methyl-sn
      glycero-3-phosphocholine.
AB  - The ether-lipid 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH3)
      has anticancer activity, but systemic toxicity has restricted its therapeutic
      use. In this report "free" ET-18-OCH3 and a stable, well-characterized, liposome
      based formulation of ET-18-OCH3 (ELL-12) were compared for in vivo toxicity in
      normal mice and for therapeutic efficacy in three mouse tumor model systems. The
      entrapment of ET-18-OCH3 in liposomes decreased the acute toxicity of ET-18-OCH3
      after i.v. administration. The maximum tolerated dose for a single i.v. dose of
      free ET-18-OCH3 was found to be approximately 25 mg/kg, whereas the maximum
      tolerated dose for ELL-12 was approximately 200 mg/kg. ELL-12 was much less
      hemolytic in vivo than ET-18-OCH3. The therapeutic efficacy of free ET-18-OCH3
      and ELL-12 was investigated against i.p. P388 leukemia, Lewis lung cancer lung
      metastases, and B16/F10 melanoma (lung tumor nodules) in mice. Although ET-18
      OCH3 had some anticancer activity, it was found that ELL-12 was more effective
      than ET-18-OCH3 in all three tumor models at lower and nontoxic dose schedules.
      These results suggest that association of ET-18-OCH3 in stable, well
      characterized liposomes transforms it into an effective antitumor agent.

PMID- 9157986
TI  - Tumor cell targeting with antibody-avidin complexes and biotinylated tumor
      necrosis factor alpha.
AB  - Tumor pretargeting with biotinylated antibodies and avidin, followed by a delayed
      delivery of radioactive-labeled biotin, is currently used for in vivo diagnosis
      and therapy in cancer patients. Herein, we describe the use of a three-step
      antibody/avidin targeting approach to increase the local concentration and the
      persistence of biotinylated human tumor necrosis factor alpha (bio-TNF) on a
      mouse tumor. Mouse RMA lymphoma cells were transfected with the Thy 1.1 allele
      (RMA-Thy 1.1) to generate a unique tumor-associated antigen. In vitro
      pretargeting of RMA-Thy 1.1 cells with the biotinylated anti-Thy 1.1 monoclonal
      antibody 19E12 (bio-19E12) and NeutrAvidin increased the amount of bio-TNF that
      bound to the cell (10-20 times in comparison with non-pretargeted cells), as well
      as its half-life on the surface (>30 times). Furthermore, cell pretargeting
      reduced by more than 2 orders of magnitude the LD50 of bio-TNF in a cytolytic
      assay with actinomycin D. Finally, RMA-Thy 1.1 cells, pretreated in vitro with
      bio-TNF according to the three-step procedure and injected into syngeneic C57/BL6
      mice, were less tumorigenic than controls. These results indicate that the three
      step targeting approach markedly increases the amount and the persistence of bio
      TNF on the cell surface and that cell-bound bio-TNF can trigger cytolytic effects
      in vitro and antitumor effects in vivo. Tumor pretargeting with biotinylated
      antibodies and avidin could be a novel strategy for increasing the therapeutic
      index of TNF.

PMID- 9157987
TI  - Potentiation of murine MCa-4 carcinoma radioresponse by 9-amino-20(S)
      camptothecin.
AB  - 9-Amino-20(S)-camptothecin (9-AC) has demonstrated efficacy against several human
      cancer xenografts, including cancers of the colon, breast, lung, ovary, and
      stomach and malignant melanoma, and is currently undergoing Phase I clinical
      trials. In vitro data indicate that the addition of topoisomerase I inhibitors
      shortly after irradiation causes conversion of single-strand breaks to double
      strand breaks, resulting in synergistic lethality to cultured log-phase or
      quiescent malignant cells. In our study, the efficacy of 9-AC as a potential
      radiosensitizing agent in vivo was assessed in C3Hf/Kam female mice bearing 7.6-8
      mm MCa-4 mammary tumors implanted i.m. into the right posterior thigh. In one
      series of experiments to determine the dose dependence of 9-AC, mice were
      injected twice a week with either 0.5, 1.0, or 2.0 mg/kg 9-AC (total doses of 2,
      4, and 8 mg/kg, respectively) either alone or 1 h before irradiation. In a second
      series of experiments, the schedule dependence of 9-AC was determined by giving a
      constant total dose of 4 mg/kg 9-AC once (2 mg/kg), twice (1 mg/kg every third
      day), or four (0.5 mg/kg every other day) times per week for 2 weeks, either
      alone or combined with radiation. The same radiation regimen was used in all
      experiments: 2-Gy fractions daily for 14 consecutive days, giving a total dose of
      28 Gy to the tumor-bearing leg only. Tumor response was assessed by regrowth
      delay and dose modification factors (DMFs) obtained by comparing regrowth delay
      in the groups given 9-AC alone with those given the same dose of 9-AC and
      radiation. 9-AC significantly delayed tumor growth when combined with radiation,
      and this effect was dependent on drug dose; DMFs of 2.4 [95% confidence interval
      (CI), 2.0-3.1], 3.7 (95% CI, 3.1-4.6), and 3.3 (95% CI, 2.7-4.1) were obtained
      for groups treated with total drug doses of 2.0, 4.0, and 8.0 mg/kg 9-AC,
      respectively. In addition, the same total dose of 4 mg/kg 9-AC was more effective
      when given either twice or four times a week compared with once a week, giving
      DMFs of 2.8 (95% CI, 2.2-3.9), 2.6 (95% CI, 2.0-3.6), and 1.7 (95% CI, 1.3-2.4),
      respectively. The effect of 9-AC and radiation on normal tissue toxicity was
      assessed in two normal tissues, jejunum and skin, in separate groups of mice.
      Jejunal crypt cell survival was decreased in those mice given single doses of 9
      AC ranging from 0.5-4.0 mg/kg and 12.5 Gy of total body radiation compared with
      those given 12.5 Gy of total body irradiation alone. The same regimen of drug and
      radiation did not modify acute skin reactions. These results suggest that 9-AC is
      an effective in vivo radiosensitizing agent when given in divided doses with
      fractionated irradiation. In addition, the gastrointestinal tract but not skin
      could be a critical target tissue for the use of 9-AC combined with radiation.

PMID- 9157989
TI  - Germinal center-derived signals act with Bcl-2 to decrease apoptosis and increase
      clonogenicity of drug-treated human B lymphoma cells.
AB  - Bcl-2 suppresses drug-induced apoptosis in vitro, although in many cases, this
      results only in a delayed onset of cell death. In vivo survival signals from the
      extracellular environment may also contribute to drug resistance and may act with
      Bcl-2 to promote long-term cell survival. Ligation of CD40 on B-lymphocytes in
      germinal centers (GCs) can suppress apoptosis induced by calcium ionophore or
      anti-IgM in vitro. We asked whether a combination of Bcl-2 expression and the
      provision of a culture environment that mimicked that of the GC [CD40 ligation
      and interleukin 4 (IL-4)] could increase the ability of B lymphoma cells to
      resist drug-induced apoptosis. A Burkitt lymphoma (BL) cell line transfected with
      either human bcl-2 (BL-bcl-2) or control plasmid (BL-Sv2) was used to examine the
      effects of Bcl-2 overexpression on the cellular response and long-term survival
      after treatment with the DNA-alkylating drug chlorambucil (CMB) in the presence
      or absence of CD40 ligation and IL-4. Administration of 20 microM CMB completely
      prevented cell proliferation. This was associated with an increase in p53 protein
      levels within 24 h, without an elevation in p21, Bax, or Mdm2 proteins. Analyses
      of cell cycle distribution and of cyclin B expression demonstrated that both cell
      lines arrested at G2/M, where they died. Fifty % of BL-Sv2 cells died within 2
      days, whereas 50% cell death was not observed in the BL-bcl-2 cultures until 6
      days had passed. Cross-linking of CD40 with a monoclonal antibody elevated Bcl-xL
      protein levels by 3 h and also provided a delay in CMB-induced death. Ninety-six
      h after the addition of 20 microM CMB, 78% of the BL-Sv2 cells were apoptotic,
      whereas ligation of CD40 on BL-Sv2 cells reduced the proportion of apoptotic
      cells to 38%. Overexpression of Bcl-2 (in BL-bcl-2 cells) reduced apoptosis to
      41%. However, when the BL-bcl-2 cells were treated with CMB together with
      ligation of CD40, apoptosis was reduced further to only 17% at 96 h. The Bcl-2
      mediated delay in the execution of CMB-induced apoptosis did not translate
      significantly to increased clonogenicity. In contrast, the provision of BL-Sv2
      cells with an ability to interact with the adhesion molecule vascular cell
      adhesion molecule-1, CD40 ligation, and IL-4 significantly increased clonogenic
      survival, and this was improved in BL-bcl-2 cells exposed to these GC-derived
      signals. These data demonstrate that the kinetics of drug-induced apoptosis can
      be modulated by Bcl-2 as well as by IL-4, vascular cell adhesion molecule-1, and
      CD40 ligation, the latter possibly involving the function of Bcl-xL. That these
      factors appear to act together to enhance proliferative potential after DNA
      damage has important implications regarding the development of drug resistance in
      B-cell lymphomas and future strategies for improved chemotherapy.

PMID- 9157988
TI  - Multiplicity of biliary excretion mechanisms for irinotecan, CPT-11, and its
      metabolites in rats.
AB  - We have reported previously that a canalicular multispecific organic anion
      transporter (cMOAT) is responsible for the biliary excretion of carboxylate forms
      of irinotecan, 7-ethyl-10-[4-(1-piperidino)-1 piperidino] carbonyloxy
      camptothecin (CPT-11), its active metabolite SN-38, and glucuronide conjugate
      (SN38-Glu) and the lactone form of SN38-Glu in rats. In this paper, the
      multiplicity of biliary excretion mechanisms for these four anionic compounds was
      investigated using isolated liver bile canalicular membrane vesicles (CMVs)
      obtained from Sprague Dawley rats. For the carboxylate form of CPT-11 and the
      lactone and carboxylate forms of SN38-Glu, ATP-dependent uptake consisted of both
      high- and low-affinity components in CMVs. Mutual inhibition studies with S-(2,4
      dinitrophenyl)glutathione, a representative substrate for cMOAT, and the uptake
      study using CMVs from Eisai hyperbilirubinemic rats revealed that cMOAT is
      responsible for the biliary excretion of the low-affinity component of the
      carboxylate form of CPT-11 and the high-affinity component of both the lactone
      and carboxylate forms of SN38-Glu, whereas the high-affinity component for CPT-11
      and the low-affinity component for SN38-Glu, which are expressed in Eisai
      hyperbilirubinemic rats, are governed by a transporter different from cMOAT. The
      carboxylate form of SN-38 was found to be transported by cMOAT alone. We conclude
      that multiple transporters, including cMOAT, are responsible for the biliary
      excretion of CPT-11 and its metabolites (anionic forms), and the contribution of
      each transporter differs greatly, depending on the substrates.

PMID- 9157990
TI  - Enhanced cyclophosphamide and ifosfamide activation in primary human hepatocyte
      cultures: response to cytochrome P-450 inducers and autoinduction by
      oxazaphosphorines.
AB  - The anticancer oxazaphosphorine prodrugs cyclophosphamide and ifosfamide are
      activated in human liver by a 4-hydroxylation reaction catalyzed by multiple
      cytochrome P450 (CYP) enzymes. In the present study, we used a cultured human
      hepatocyte model to identify possible inducers of the CYP-catalyzed activation of
      these two anticancer prodrugs. Treatment of primary cultures of human hepatocytes
      with phenobarbital, dexamethasone, or rifampin elevated hepatocyte microsomal
      oxazaphosphorine 4-hydroxylation by up to 200-400% of control for both drug
      substrates. These inductions were associated with corresponding increases in
      immunoreactive CYP2B6, CYP2C8, CYP2C9, and CYP3A4, all previously shown to
      catalyze oxazaphosphorine activation. Rifampin (1 microM, 96-h exposure) was a
      particularly potent inducer of ifosfamide and cyclophosphamide 4-hydroxylation,
      as well as of CYP3A protein levels and CYP3A-dependent testosterone 6beta
      hydroxylation. CYP3A4, CYP2C8, and CYP2C9 protein levels were also increased by
      exposure of the hepatocytes to cyclophosphamide or ifosfamide (50 microM), which
      thereby enhanced their own rates of 4-hydroxylation in the cultured hepatocytes.
      In one human hepatocyte culture that contained the polymorphically expressed
      CYP3A5 in addition to the more widely expressed CYP3A4, only CYP3A4 was induced
      by cyclophosphamide, ifosfamide, and rifampin. These studies: (a) demonstrate an
      underlying metabolic basis for the clinically important oxazaphosphorine
      autoinduction pharmacokinetics seen with these drugs in cancer patients; and (b)
      identify rifampin and other CYP inducers as potentially useful for increasing the
      rates of cyclophosphamide 4-hydroxylation and ifosfamide 4-hydroxylation in human
      liver in a manner that could favorably impact the clinical pharmacokinetics of
      these anticancer prodrugs.

PMID- 9157991
TI  - Improved biodistribution of 125I-labeled anti-Tac disulfide-stabilized Fv
      fragment by blocking its binding to the alpha subunit of the interleukin 2
      receptor in the circulation with preinjected humanized anti-Tac IgG.
AB  - Animal studies using radiolabeled anti-Tac disulfide-stabilized Fv (dsFv)
      monoclonal antibody have shown formation of complexes in serum with the soluble
      alpha subunit of the interleukin 2 receptor alpha (sIL-2R alpha). In this study,
      we improved the targeting of 125I-labeled anti-Tac dsFv to receptor-positive
      tumors in the presence of circulating receptor by preinjecting unlabeled
      humanized anti-Tac IgG antibody (HuTac IgG). We used mice bearing SP2/Tac tumor
      xenografts that express the IL-2R alpha. A positive correlation was seen between
      tumor size and the concentration of circulating receptor. Tumor-bearing mice were
      injected with 125I-labeled anti-Tac dsFv (400 ng), either alone or 15 min after
      injection of HuTac IgG. The 125I-labeled anti-Tac dsFv formed high molecular
      weight complexes with the sIL-2R alpha. The fraction of the dsFv present in the
      complexes increased as tumor size increased (greater sIL-2R alpha levels). The
      fractions of dsFv in the complexes were 9.9- to 11.6-fold higher when sIL-2R
      alpha was not blocked with preinjected HuTac IgG. The administration of a 12-fold
      molar excess of HuTac IgG over sIL-2R alpha resulted in >80% of the 125I activity
      present as the dsFv rather than in the complexes. Furthermore, the
      biodistribution of 125I-labeled anti-Tac dsFv was improved by blocking its
      binding to sIL-2R alpha by preinjecting HuTac IgG. Specifically, in the
      preinjected group, at 15 min postinjection, the 125I-labeled anti-Tac dsFv levels
      in tumor increased to 10.8% compared to 5.6% injected dose per gram in the non
      preinjected group. In summary, our studies showed that preinjection of HuTac IgG
      can block the formation of complexes of circulating sIL-2R alpha and 125I-labeled
      anti-Tac dsFv. This blockade is associated with faster blood clearance, higher
      tumor uptake, and greater tumor:nontumor ratios of the radiolabeled antibody
      fragment.

PMID- 9157993
TI  - A persistent double-strand break destabilizes human DNA in yeast and can lead to
      G2 arrest and lethality.
AB  - Double-strand breaks (DSBs) are an important source of genomic change in many
      organisms. We have examined the consequences of a persistent versus a rapidly
      repaired DSB on cell progression, viability, and stability of human DNA contained
      in dispensable yeast artificial chromosomes (YACs) within the yeast Saccharomyces
      cerevisiae. An Alu-URA3-YZ integrating plasmid was used to target the YZ sequence
      to repetitive Alu sequences within the human YAC. The YZ site can be cut by an
      inducible HO-endonuclease resulting in a DSB. Two classes of DSBs had been
      identified previously: those that could be rapidly repaired (RR-DSB), through
      recombination between flanking Alus; and persistent DSBs (C. B. Bennett et al.,
      Mol. Cell. Biol., 16: 4414-4425, 1996). These persistent DSBs (type 1) resulted
      in G2 delay and lethality. A third class of DSB is now identified corresponding
      to a persistent DSB that does not lead to G2 arrest or lethality (type 2). Unlike
      YACs in which the DSB was rapidly repaired, the two types of persistent DSBs
      destabilized the human YAC DNA, resulting in a high likelihood of YAC loss
      (approximately 85% of surviving colonies). Furthermore, both types of persistent
      DSBs could be misrepaired, resulting in mostly large internal or terminal
      deletions in the retained YACs. Therefore, recovery of these altered YACs can
      occur regardless of the effect of the DSBs on G2 arrest and cell lethality. If
      similar events occur in mammalian cells, persistent DSBs could be the initiating
      events that lead to a loss of heterozygosity and the expression of recessive
      oncogenes seen in malignant cells.

PMID- 9157992
TI  - Mutational activation of pp60(c-src) leads to a tumorigenic phenotype in a
      preneoplastic Syrian hamster embryo cell line.
AB  - Previous studies indicated that overexpression of wild-type avian c-src cannot
      induce neoplastic transformation of NIH 3T3 cells. In this study, we isolated and
      characterized novel spontaneously derived transforming mutants of avian pp60(c
      src) from a Syrian hamster embryo-derived cell line, 10W, transfected with the
      avian c-src gene. Seventeen independently derived transfected 10W cell clones
      were injected into athymic nude mice. After a latency period, tumors eventually
      arose and were established in culture. The tumorigenic phenotype was always
      accompanied by the presence of the avian c-src DNA and functional expression of
      pp60(c-src). However, most of the tumor-derived cell lines expressed an
      electrophoretically altered form of pp60(c-src), suggesting mutations in src.
      Consistent with this hypothesis, DNAs isolated from the tumor-derived lines, but
      not the parental 10W cell lines, morphologically transformed NIH 3T3 cells in a
      focus-forming assay. We characterized pp60(c-src) in detail from three of the
      tumor-derived lines: 4AT, 4BT, and E2T. Two of these lines contained mutations
      within the exogenous c-src coding region. Line 4AT has an internal repeat of 29
      amino acids immediately following Gln-513, which disrupts the spacing between the
      end of the kinase domain and Tyr-527, the negative regulatory site in pp60(c
      src). Line 4BT has a 5-bp deletion following Phe-520, which results in loss of
      Tyr-527. However, the DNA sequence of the coding region of pp60(c-src) from a
      third line, E2T, was completely wild type. Cyanogen bromide cleavage analyses of
      the altered pp60(c-src) from lines 4AT and 4BT showed that Tyr-527, the site of
      negative regulation of c-src, is not phosphorylated, but Tyr-416, the site of in
      vitro autophosphorylation, is phosphorylated. However, in line E2T, Tyr-527 was
      phosphorylated, and Tyr-416 was phosphorylated to a lesser extent. Additionally,
      two proteins that indicate activation of src, p85 cortactin and p120(cas), are
      phosphorylated in at least six of the tumor-derived cell lines, although to a
      lesser extent in line E2T. These results suggest that dephosphorylation of Tyr
      527 and phosphorylation of Tyr-416 correlate with activation of pp60(c-src) in
      the tumor-derived lines 4AT and 4BT, respectively. However, in line E2T, the high
      levels of pp60(c-src), in combination with a partial activation of the pp60(c
      src) protein as indicated by phosphorylation of Tyr-416, appear to be involved in
      the neoplastic process, rather than mutation.

PMID- 9157994
TI  - Abnormal FHIT transcripts in human breast carcinomas: a clinicopathological and
      epidemiological analysis of 61 Japanese cases.
AB  - Deletions in the short arm of chromosome 3 have been found in various human
      cancers, including breast cancer. Recently, the FHIT (fragile histidine triad)
      gene was identified at 3p14.2 as a candidate tumor suppressor gene. We examined
      the abnormal transcripts of the FHIT gene in 61 Japanese primary breast cancer
      specimens and found that 23 (38%) of them exhibited abnormalities, about half of
      which were categorized into two types of aberrant transcripts. Sequence analysis
      of these aberrant transcripts revealed the absence of exons 5-7 (type I) and
      exons 5-8 (type II). Clinicopathological and epidemiological analysis of patients
      showed that the abnormal FHIT transcripts were not associated with age, tumor
      node-metastasis classification, tumor size, estrogen receptor and progesterone
      receptor status, local metastasis, family history of breast cancer, or lifestyle
      factors of patients, including cigarette smoking and alcohol consumption. On the
      other hand, we found that the abnormal transcripts of type I and type II were
      associated with the incidence of bilateral breast cancer and that decreased
      frequency of childbirth was also associated with FHIT abnormalities.

PMID- 9157995
TI  - Concerted nonsyntenic allelic losses in hyperploid hepatocellular carcinoma as
      determined by a high-resolution allelotype.
AB  - Although the occurrence of loss of genetic material in hepatocellular carcinoma
      (HCC) has been documented both by cytogenetic analysis and by monitoring of
      allelic losses, a global overview of the extent and frequency of deletion
      occurring throughout the genome is not yet available. To contribute to this
      information, DNAs extracted from flow-sorted aneuploid nuclei from HCC and
      matched normal DNAs were typed for 275 microsatellite loci that were distributed
      along the autosomes. An average of 190 (69%) informative loci per case were
      generated on 48 HCC. Complete loss of heterozygozity in the tumor DNA was
      observed for 15.6% of the typed loci. The chromosome segments that were most
      frequently affected by deletion were: 8p (60%), 17p (48%), 1p (44%), 4q (42%),
      16p (40%), 16q (39%), 6q (35%), 9p (30%), and 13q (29%). On average, 8 of the 39
      chromosome segments studied per tumor carried at least one locus that
      demonstrated loss of heterozygosity (ie., the fractional allelic loss was 0.21).
      Groups of concerted nonsyntenic losses were observed for 16p and 1p and for 16p
      and 4q. The location of putative tumor suppressor genes on the most frequently
      deleted regions was confirmed and, in some cases, refined.

PMID- 9157997
TI  - Somatic mutational mechanisms involved in intestinal tumor formation in Min mice.
AB  - We have demonstrated previously that intestinal tumor formation in B6 Min/+ mice
      is always accompanied by loss of the wild-type adenomatous polyoposis coli (Apc)
      allele and that intestinal tumor multiplicity in B6 Min/+ mice can be
      significantly increased by treatment with a single dose of N-ethyl-N-nitrosourea
      (ENU). Here, we show that some tumors from ENU-treated Min/+ mice can form
      without complete elimination of Apc+. At least 25% of these tumors acquired
      somatic Apc truncation mutations. Interestingly, some ENU-induced tumors
      demonstrated loss of the Apc+ allelic marker examined by the quantitative PCR
      assay used here. Using two methods of mutation detection, we identified no Apc
      mutations in at least 12% of the tumors from ENU-treated B6 Min/+ mice. Finally,
      no H- or K-ras-activating mutations were detected in intestinal tumors from
      either untreated or ENU-treated Min/+ mice. The majority of somatic human APC
      mutations in intestinal tumors lead to APC truncation. Our results demonstrate
      that somatic Apc truncation mutations also frequently occur in ENU-induced
      intestinal tumors in Min mice.

PMID- 9157996
TI  - Overexpression of manganese-containing superoxide dismutase confers resistance to
      the cytotoxicity of tumor necrosis factor alpha and/or hyperthermia.
AB  - Human breast cancer cells (MCF-7) overexpressing manganese-containing superoxide
      dismutase (MnSOD) by stable or transient transfection were challenged with the
      cytotoxicity of tumor necrosis factor alpha (TNF-alpha), hyperthermia, and a
      combination of both. In contrast to the vector control and wild-type MCF-7 cells,
      the stable MnSOD transfectants showed significant resistance to the cytotoxicity
      of TNF-alpha (100 units/ml), heat at 43 or 45 degrees C, and a combination of TNF
      alpha and heat at 43 degrees C. To probe the correlation of MnSOD levels with
      cell survival, cell sensitivity to TNF-alpha, heat at 43 degrees C, or a
      combination of both was also measured after MnSOD cDNA transient transfection.
      The data showed that the level of cell resistance was proportional to the
      exogenous MnSOD gene expression. These results suggest that superoxide free
      radicals or their reaction products are responsible for much of the synergistic
      cytotoxicity of TNF-alpha and hyperthermia.

PMID- 9157998
TI  - Creation of human alkyltransferases resistant to O6-benzylguanine.
AB  - O6-benzylguanine (BG), an inhibitor of O6-alkylguanine-DNA alkyltransferase, is
      being tested clinically for its ability to chemosensitize tumors to alkylating
      agents. Although this drug may increase the killing of tumors that express high
      levels of alkyltransferase, it would also be expected to reduce the already low
      alkyltransferase levels of hematopoietic stem cells and, thus, exacerbate the
      dose-limiting side effect of myelosuppression. One way to overcome this problem
      would be to transduce hematopoietic stem cells with a gene encoding a BG
      resistant alkyltransferase prior to BG/alkylation treatment. We used the
      technique of random mutagenesis followed by positive genetic selection to create
      such a mutant gene. A pool of 6.5 x 10(6) human alkyltransferases that were
      randomly mutated at six amino acids near the alkyl-accepting cysteine was
      transformed into alkyltransferase-deficient Escherichia coli. Five mutants were
      selected based on their ability to provide the bacteria with resistance to both N
      methyl-N'-nitro-N-nitrosoguanidine and BG. One mutant, V139F/P140R/L142M, not
      only had the highest BG resistance (50% inhibitory concentration, >500 microM)
      but also offered E. coli the best protection from N-methyl-N'-nitro-N
      nitrosoguanidine and, thus, is a promising gene therapy candidate.

PMID- 9157999
TI  - Inhibition of vascular endothelial growth factor-induced endothelial cell
      migration by ETS1 antisense oligonucleotides.
AB  - Vascular endothelial growth factor (VEGF) increased the level of ETS1 mRNA in
      human umbilical vein endothelial cells (HUVEC) and human lung microvascular
      endothelial cells (HMVEC-L) over 5-fold. Protein levels were shown to increase
      concordantly. VEGF was also found to stimulate the invasiveness of endothelial
      cells as measured by migration through Matrigel- or gelatin-coated membranes. The
      VEGF-induced invasiveness was inhibited by ETS1 antisense oligonucleotides but
      not by a sense control. In addition, the ETS1 antisense oligonucleotides reduced
      the levels of ETS1 and urokinase-type plasminogen activator mRNAs. The antisense
      oligonucleotides directed against the ETS1 gene thus altered a cellular property
      of endothelial cells that is correlated with the ability of the cells to migrate
      through basement membranes. Together, these observations demonstrate a direct
      role for the ETS1 gene in angiogenesis.

PMID- 9158001
TI  - Identification of a gene containing zinc-finger motifs based on lost expression
      in malignantly transformed rat ovarian surface epithelial cells.
AB  - We have used a rat model of epithelial ovarian cancer to identify a gene that
      shows decreased or lost expression in five of eight independently transformed rat
      ovarian surface epithelial cell lines compared to the normal progenitor cells.
      Hence, we refer to this gene as Lot1 (lost on transformation 1; GenBank accession
      no. U72620). The most abundant transcript of the gene is approximately 6 kb. This
      sequence contains a 1749-nucleotide open reading frame and, within the 3'
      untranslated region, 22 near-perfect 60-70-bp repeats and adenine- and uracil
      rich areas. The deduced amino acid sequence from the open reading frame contains
      seven zinc-finger motifs of the C2H2 type, as well as proline-, glutamine-, and
      glutamic acid-rich areas. The gene maps to the short arm of chromosome one in the
      rat. Lot1 shows a limited distribution of expression in normal rat tissues,
      including ovary, which shows abundant expression. Furthermore, examination of DNA
      derived from multiple species indicates that the gene is widely conserved.

PMID- 9158000
TI  - Increasing c-FMS (CSF-1 receptor) expression decreases retinoic acid
      concentration needed to cause cell differentiation and retinoblastoma protein
      hypophosphorylation.
AB  - Increasing the expression of c-FMS (colony-stimulating factor 1 receptor) by
      introduction of a transgene reduced the concentration of retinoic acid or 1,25
      dihydroxy vitamin D3 needed to cause myeloid or monocytic cell differentiation
      and hypophosphorylation of the retinoblastoma tumor suppressor protein (RB)
      typically associated with cell cycle G0 arrest and differentiation of HL-60 human
      myelo-monoblastic precursor cells. The data are consistent with a model in which
      signals originating with retinoic acid and c-FMS integrate to cause
      differentiation, RB hypophosphorylation, and G0 arrest. Furthermore, these two
      signals can compensate for each other. Three HL-60 sublines described previously
      (A. Yen et al., Exp. Cell Res., 229: 111-125, 1996) expressing low (wild-type HL
      60), intermediate, and high cell surface c-FMS were treated with various
      concentrations of retinoic acid. The lowest concentration tested, 10(-8) M,
      induced significant differentiation of only the high c-FMS-expressing cells, with
      no accompanying hypophosphorylated RB or G0 arrest. The low and intermediate c
      FMS expressing cells showed no induced differentiation, hypophosphorylation of
      RB, or G0 arrest. A 10-fold higher retinoic acid concentration, 10(-1) M, induced
      significant differentiation of both intermediate and high c-FMS-expressing cells.
      It induced RB hypophosphorylation only in high c-FMS-expressing cells but with no
      accompanying G0 arrest in any of the cells. The highest retinoic acid
      concentration, 10(-6) M, elicited differentiation, hypophosphorylation of RB, and
      G0 arrest in low, intermediate, and high c-FMS-expressing cells. As the
      concentration of retinoic acid increased, cell differentiation,
      hypophosphorylation of RB, and G0 arrest were progressively elicited within this
      ensemble of cells with different c-FMS expression levels. Thus, for example, at
      the lowest concentration of retinoic acid, expression of high enough c-FMS still
      allowed differentiation. At higher concentrations, progressively less c-FMS was
      needed for differentiation. The apparent threshold for the sum of the retinoic
      acid plus c-FMS originated signals to elicit differentiation, hypophosphorylation
      of RB, and G0 arrest increased, in that order. Thus retinoic acid-induced cell
      differentiation, RB hypophosphorylation, and G0 arrest have different signal
      threshold requirements. 1,25-Dihydroxy vitamin D3, also a ligand for a member of
      the steroid thyroid hormone receptor superfamily, caused monocytic
      differentiation with a similar c-FMS dependency, indicating that these effects
      characterize both myeloid and monocytic differentiation.

PMID- 9158002
TI  - The human ALL-1/MLL/HRX antigen is predominantly localized in the nucleus of
      resting and proliferating peripheral blood mononuclear cells.
AB  - The ALL-1 gene is an important regulator of embryonal and hematopoietic
      development, and structural variants of the human gene generated by chromosomal
      translocations and other genomic alterations presumably act as oncogenes in the
      pathogenesis of acute leukemias and other hematological malignancies. Antisera
      against two different epitopes of the human ALL-1 protein (anti-ALL1-N and anti
      ALL1-C) were produced. Both sera revealed indistinguishable patterns of antigen
      localization in human peripheral blood mononuclear cells (PBMCs). In resting
      PBMCs, the antigen was distributed in a speckled pattern across the nuclei, with
      an increased density at the nuclear envelope and the nuclear indentation. In
      mitotically stimulated PBMCs, the antigen surrounded the condensing chromosomes
      but did not colocalize with chromatin or the nuclear scaffold. The antigen is
      considered a marker for a novel nuclear subcompartment, a perichromosomal area
      termed the "chromosomal envelope." In Western blot experiments, the anti-ALL1-N
      serum reacted with a polypeptide corresponding to the expected full-length 430
      kDa ALL-1 protein. Recombinant proteins representing the AT-hook and zinc binding
      subdomains of the ALL-1 protein interacted in vitro with a degenerate mixture of
      double-stranded oligodeoxynucleotides. Thus, the ALL-1 protein probably is a DNA
      binding protein with both a sequence-unspecific (AT-hook) and a sequence-specific
      (zinc binding subdomains) double-stranded DNA binding mode.

PMID- 9158003
TI  - Cancer invasion and micrometastasis visualized in live tissue by green
      fluorescent protein expression.
AB  - We report the establishment of stable, high-level green fluorescent protein (GFP)
      expressing cell lines in vitro that permit the detection and visualization of
      distant micrometastases when they are implanted orthotopically in nude mice.
      Chinese hamster ovary cells were transfected with the dicistronic expression
      vector containing the humanized GFP cDNA. A stable GFP-expressing clone was
      selected in 1.5 microM methotrexate in vitro and injected s.c. in nude mice.
      Stable high-level expression of GFP was maintained in the s.c. growing tumors. To
      use GFP expression for metastasis studies, fragments of s.c. growing tumor, which
      are comprised of GFP-expressing cells, were implanted by surgical orthotopic
      implantation in the ovary of nude mice. Subsequent micrometastases were detected
      in systemic organs and could be visualized by GFP fluorescence in the lung,
      liver, and other organs down to the single-cell level. With this fluorescent
      tool, we detected and visualized for the first time tumor cells at the
      microscopic level in fresh viable tissue in their normal host organ. Confocal
      microscopy further enabled us to study physiologically relevant patterns of
      invasion and micrometastasis.

PMID- 9158004
TI  - Disrupted IGF2 promoter control by silencing of promoter P1 in human
      hepatocellular carcinoma.
AB  - Previous investigations have supported or indicated a stimulatory role of the
      insulin-like growth factor II gene (IGF2) in hepatocarcinogenesis. We have
      studied the transcript levels, promoter usage, and imprinting status of the ICF2
      gene and its relationship to H19 in human hepatocellular carcinomas (HCCs) and
      liver tumor cell lines. The activity of the IGF2 promoter P1 was lost in about
      70% of the cases (18 of 25). This is the most prominent abnormality regarding the
      IGF2 regulation in this study. Total IGF2 as well as promoter P3 transcription
      were up-regulated in a small group of the tumors. Twenty genetically informative
      cases were obtained from 26 cases, thus excluding the probability of loss of
      heterozygosity of the IGF2 gene. Among these, nine showed abnormal monoallelic
      expression of IGF2. One HCC and one HCC cell line proved loss of functional
      imprinting of IGF2. H19 and IGF2 were regulated in parallel, and expression
      levels were variable. Taken together, the disruption of the IGF2 promoter
      regulation, particularly the loss of P1 activity, is a common feature of human
      HCCs. The loss of P1 activity explains the frequent loss of biallelic IGF2
      expression and may potentially be used as a diagnostic or monitoring marker for
      human HCC.

PMID- 9158005
TI  - Expression and tissue localization of membrane-types 1, 2, and 3 matrix
      metalloproteinases in human invasive breast carcinomas.
AB  - Activation of the zymogen of matrix metalloproteinase 2 (proMMP-2, progelatinase
      A) possibly is one of the key steps in invasion and metastasis of various human
      carcinomas. Three different membrane-type MMPs (MT-MMPs), MT1-, MT2-, and MT3
      MMPs are thought to be activators of proMMP-2 in the tissues. MT4-MMP is
      structurally different from the other three enzymes, and its function as proMMP-2
      activator is uncertain. In the present study of human invasive breast carcinomas,
      we examined a correlation between the expression of MT1-, MT2-, and MT3-MMPs,
      immunolocalization of MT1- and MT2-MMPs, and proMMP-2 activation. Northern blot
      analysis demonstrated the predominant expression of MT1-MMP mRNA in carcinoma
      tissues (20 of 20 cases), whereas MT2-MMP was detected in only 25% of the cases
      (5 of 20 cases), and no detectable expression of MT3-MMP was observed. The
      expression levels of MT1-MMP but not MT2-MMP correlated well with the presence of
      lymph node and distant metastases, clinical stages, and size of tumors.
      Immunohistochemically, MT1-MMP was localized predominantly in the carcinoma cells
      in all of the samples (32 of 32 cases). Immunostaining of MT2-MMP in the
      carcinoma cells was observed in only 38% of the cases (12 of 32 cases).
      Immunoblot analysis of tumor homogenates confirmed the presence of these MT-MMPs.
      Activation of proMMP-2 was significantly higher in the carcinoma samples with
      lymph node or distant metastasis compared to carcinoma without metastasis, normal
      control, or fibrocystic disease (P < 0.05). An increase in the activation ratio
      of proMMP-2 correlated directly with the expression of MT1-MMP but not MT2-MMP,
      as measured by either Northern blot analysis or immunostaining. These results
      suggest that MT1-MMP may play a key role in human breast carcinoma invasion and
      metastasis by being predominantly responsible for activation of proMMP-2.

PMID- 9158006
TI  - Migration of highly aggressive MV3 melanoma cells in 3-dimensional collagen
      lattices results in local matrix reorganization and shedding of alpha2 and beta1
      integrins and CD44.
AB  - The three-step model of cell migration consisting of protrusion of a leading
      lamella, attachment to the substrate, and contraction of the cell body is well
      established for fibroblasts migrating across planar surfaces. However, it is not
      resolved to what extent the migration of cancer cells in a 3-dimensional tissue
      environment follows similar principles. Here, we present evidence that the
      migration of highly invasive MV3 melanoma cells in 3-dimensional collagen
      matrices follows the three-step concept of migration but also results in
      characteristic reorganization of the extracellular matrix. After incorporation in
      the lattice, MV3 cells spontaneously developed a slow type of migration (mean
      velocity, 0.19 microm/min), leading to alignment of collagen fibers at attachment
      sites, as detected from unfixed and fixed samples by confocal reflection contrast
      in combination with immunofluorescence staining. In the process of migration, the
      formation of focal clusters or stripes of alpha2 and beta1 integrins colocalized
      with binding sites to collagen fibrils at the leading as well as the trailing
      edge. In contrast, CD44 was nonclustered and redistributed toward the rear end of
      the cell. At detachment sites, dynamic fiber traction, localized fiber
      disruption, and the release of cell surface determinants, including alpha2beta1
      integrins and CD44, resulted in circumscribed matrix reorganization. Not
      infrequently, these emerging tube-like paths of least resistance bordered by a
      dense fiber network facilitated the reorientation and contact guidance of
      proximate MV3 cells to migrate along the preexisting path. In conclusion, the
      migration of MV3 cells in 3-dimensional collagen lattices resulted in dynamic
      tissue reorganization and receptor shedding the consequences of which were
      directly visualized by combining confocal reflection imaging with
      immunofluorescence.

PMID- 9158007
TI  - Human malignant thyroid tumors displayed reduced levels of transforming growth
      factor beta receptor type II messenger RNA and protein.
AB  - Transforming growth factor beta (TGF-beta) is a physiological regulator of
      thyroid epithelial cell growth and differentiation. This factor signals through a
      heteromeric complex composed of type I (TGF-beta receptor type I) and type II
      [TGF-beta receptor type II (TbetaRII)] receptors. Loss of TbetaRII expression has
      been related to resistance to TGF-beta inhibition of cell proliferation. In the
      present work, we analyzed the TbetaRII expression in a series of human thyroid
      tumors, from benign lesions (adenomas) to neoplastic lesions of increasing
      aggressiveness (papillary and follicular carcinomas) up to the extremely
      aggressive anaplastic tumors. Results obtained indicated a clear reduced
      expression of TbetaRII mRNA only in the group of thyroid carcinomas when compared
      with their relative normal tissues. Immunohistochemical analyses with specific
      anti-TbetaRII antibodies confirm these observations. These data indicate that
      loss of expression of TbetaRII can contribute to thyroid cancer progression,
      inducing cancer cells to escape the growth-inhibitory effect of TGF-beta.

PMID- 9158009
TI  - Autologous lymphokine-activated killer cell therapy of Epstein-Barr virus
      positive and -negative lymphoproliferative disorders arising in organ transplant
      recipients.
AB  - Lymphoreticular malignancies, collectively called posttransplant
      lymphoproliferative disorders (PTLD), eventually develop in 2-5% of organ
      transplant recipients. They frequently undergo regression when immunosuppression
      is reduced or stopped. This feature has been associated with a previous or de
      novo Epstein-Barr virus (EBV) infection. We herein describe immunotherapy with
      autologous lymphokine-activated killer (LAK) cells in seven patients with PTLD
      (four EBV-positive patients and three EBV-negative patients). Autologous
      peripheral blood mononuclear cells were obtained by leukapheresis, depleted of
      monocytes, and cultured in the presence of interleukin 2 for 10 to 11 days. A
      single dose of 5.2 x 10(9) to 5.6 x 10(10) LAK cells was given intravenously.
      Systemic interleukin 2 was not administered. The four patients with EBV+ PTLD had
      complete tumor regression; two of them developed controllable rejection. Three
      patients are well 13-16 months after treatment; the fourth patient died of
      pneumonia 41 days after infusion. Three patients with EBV- lymphomas had no
      response despite prior evidence that their tumors also were subject to immune
      surveillance. Two of these three patients died after being given other treatment,
      and the third patient has persistent tumor. In conclusion, autologous LAK cell
      infusion was effective for treatment of four EBV+ organ transplant recipients.
      LAK cell efficacy for three patients with EBV- PTLD was not evaluable under the
      management circumstances in which this treatment was utilized.

PMID- 9158008
TI  - Striking augmentation of hematopoietic cell chimerism in noncytoablated
      allogeneic bone marrow recipients by FLT3 ligand and tacrolimus.
AB  - The influence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and
      the recently identified hematopoietic stem-progenitor cell mobilizing factor flt3
      ligand (FL) on donor leukocyte microchimerism in noncytodepleted recipients of
      allogeneic bone marrow (BM) was compared. B10 mice (H2b) given 50x10(6)
      allogeneic (B10.BR [H2k]) BM cells also received either GM-CSF (4 microg/day
      s.c.), FL (10 microg/day i.p.), or no cytokine, with or without concomitant
      tacrolimus (formerly FK506; 2 mg/kg) from day 0. Chimerism was quantitated in the
      spleen 7 days after transplantation by both polymerase chain reaction (donor DNA
      [major histocompatibility complex class II; I-E(k)]) and immunohistochemical
      (donor [I-E(k)+] cell) analyses. Whereas GM-CSF alone significantly augmented
      (fivefold) the level of donor DNA in recipients' spleens, FL alone caused a
      significant (60%) reduction. Donor DNA was increased 10-fold by tacrolimus alone,
      whereas coadministration of GM-CSF and tacrolimus resulted in a greater than
      additive effect (28-fold increase). A much more striking effect was observed with
      FL + tacrolimus (>125-fold increase in donor DNA compared with BM alone). These
      findings were reflected in the relative numbers of donor major histocompatibility
      complex class II+ cells (many resembling dendritic cells) detected in spleens,
      although quantitative differences among the groups were less pronounced.
      Evaluation of cytotoxic T lymphocyte generation by BM recipients' spleen cells
      revealed that FL alone augmented antidonor immunity and that this was reversed by
      tacrolimus. Thus, although FL may potentiate antidonor reactivity in
      nonimmunosuppressed, allogeneic BM recipients, it exhibits potent chimerism
      enhancing activity when coadministered with recipient immunosuppressive therapy.

PMID- 9158010
TI  - Intrasplenic hepatocyte allotransplantation in dalmation dogs with and without
      cyclosporine immunosuppression.
AB  - Hepatocyte allotransplantation has been performed successfully in several small
      animal models for the amelioration of inborn metabolic errors. Before a human
      clinical trial of hepatocyte allotransplantation can be attempted, preliminary
      experience in a large animal model is needed. We transplanted isolated mongrel
      hepatocytes into the spleen of dalmatians in the attempt to cure their inborn
      error of uric acid metabolism. Of 10 dalmatian recipients, two that received 9-10
      x 10(9) mongrel hepatocytes died early after surgery of acute portal hypertension
      and hemorrhage. The eight long-term survivors received 5-6 x 10(9) hepatocytes
      and were randomized either to no treatment or to oral cyclosporine (CsA). Levels
      of CsA were adjusted to maintain trough levels between 400 and 800 ng/ml. In the
      four nonimmunosuppressed dalmatians, a reproducible average reduction in urinary
      uric acid excretion (UUAEx) of 23.7% was achieved; values returned to baseline
      within 14 days. In the CsA-immunosuppressed dalmatians, the average decline in
      UUAEx was 30%. The partial correction of the metabolic defect persisted for an
      average of 25 days in three immunosuppressed dogs, whereas in one dog, the
      partial correction lasted for over 90 days. No change in UUAEx was observed in
      two dalmatians that underwent sham laparotomy and intrasplenic injection of
      saline solution; CsA given alone to dalmatians did not modify UUAEx. We conclude
      that the dalmatian dog is a valuable large animal model for studies of the role
      of hepatocyte transplantation in the cure of inborn hepatic metabolic errors.

PMID- 9158011
TI  - Enhancement of axon growth by detergent-extracted nerve grafts.
AB  - BACKGROUND: The immunogenicity of nerve allografts is responsible for their
      rejection. We have developed a method for preparing cell-free nerve grafts using
      lysophosphatidylcholine to remove cells, axons, and myelin sheaths. METHODS: The
      remaining intact nerve extracellular matrix is the extracted nerve graft (eNG).
      Cultured neonatal Schwann cells were micro-injected into the eNG to form
      recellularized nerve grafts (rNG). eNG, rNG, and normal isografts (15 mm long)
      were implanted in the peroneal nerves of F-344 rats. Ten rats were given an eNG
      on the right, and an isograft on the left. Ten rats were given an rNG on the
      right, and a sham operation on the left. Sham operation was used as the control
      and the isograft was used as the benchmark procedure. Walking track analysis was
      performed every 15 days after surgery to determine the peroneal functional index.
      Morphometric analysis of the distal peroneal nerve and extensor digitorum muscle
      weight were analyzed 3 months after surgery. RESULTS: The three types of grafted
      legs had the classical effect observed after peripheral nerve repair, with
      decreased functional ability, decreased target muscle weight, fewer large nerve
      fibers, and more small nerve fibers. Isografts, eNG, and rNG all had similar
      patterns of peroneal functional index improvement after implantation. The
      extensor digitorum longus muscle weight and axon counts for the three types of
      graft were not statistically different. Hence, eNG and rNG can enhance nerve
      regeneration in the same way as isografts. The host Schwann cells that invaded
      the implanted eNG probably acted in the same fashion as the cultured Schwann
      cells injected into the rNG and the resident cells of isografts. CONCLUSIONS: The
      great permeability of the longitudinally oriented matrix of eNG to cells is,
      therefore, a major advantage over the reported poor permeability of freeze-thawed
      nerve grafts.

PMID- 9158012
TI  - Lazaroids prevent acute cyclosporine-induced renal vasoconstriction.
AB  - BACKGROUND: Cyclosporine (CsA)-induced nephrotoxicity may be due to intrarenal
      vasoconstriction and glomerular hypoperfusion. Several factors, including
      endothelin and prostanoids, are suggested mediators of this response. Recent
      evidence suggests that CsA leads to increased oxygen-derived free radical (ODFR)
      production and lipid peroxidation in renal tissue. Whether this leads to
      alterations in renal vessel reactivity is unclear. Lazaroids, such as U74389G,
      are radical-quenching antioxidants that inhibit ODFR-induced lipid peroxidation
      and may improve renal function after ischemia and reperfusion. We hypothesized
      that ODFRs contribute to CsA-induced alterations of the renal microcirculation.
      METHODS: Rat hydronephrotic kidneys were studied by video microscopy.
      Interlobular arteriolar diameter and flow, afferent and efferent arteriolar
      diameters, and cardiac output were measured at 15-min intervals for 120 min.
      U74389G or its vehicle was infused 15 min before topical application of CsA to
      the kidney. The results were compared with U74389G alone and normal saline.
      RESULTS: CsA administration caused renal microvascular vasoconstriction (10-25%
      below baseline) and hypoperfusion (35% below baseline). Both vasoconstriction and
      hypoperfusion were significantly attenuated by U74389G (5-8% and 20% below
      baseline, respectively). CONCLUSIONS: Inhibition of lipid peroxidation by U74389G
      maintained renal blood flow during acute CsA administration. These data suggest
      that ODFRs are involved in the renal microvascular response to CsA. Inhibition of
      ODFR-induced lipid peroxidation may help prevent CsA-induced glomerular
      hypoperfusion. Lazaroids may prove an effective adjunct in reducing CsA-induced
      nephrotoxicity.

PMID- 9158013
TI  - Budesonide, a locally acting steroid, prevents graft rejection in a rat model of
      intestinal transplantation.
AB  - BACKGROUND: The requirement for potent systemic immunosuppression to prevent
      intestinal graft rejection has resulted in high rates of infection and post
      transplant lymphoproliferative disease. Budesonide (BUD) is a locally acting
      steroid that is almost completely metabolized during its first pass through the
      intestinal wall and liver. The present study examined whether BUD could prevent
      small bowel allograft rejection without causing the adverse systemic effects
      associated with prednisolone. METHODS: Orthotopic Brown Norway to Lewis rat small
      bowel allotransplants were randomly assigned to treatment with low-dose BUD (0.1
      mg/kg/day, p.o.) and high-dose BUD (1.0 mg/kg/day, p.o.) with and without
      cyclosporine (CsA; 2 mg/kg/day s.c.). The following parameters were assessed:
      allograft survival, recipient plasma adrenocorticotrophic hormone (ACTH) levels,
      recipient adrenal, splenic and thymic weights, recipient CsA levels, and graft
      histopathology. RESULTS: Low- and high-dose BUD alone did not prolong graft
      survival compared with the untreated group (9.1+/-0.4 days vs. 11+/-0.8 days vs.
      9.7+/-0.4 days, respectively). However, when low-dose BUD and high-dose BUD were
      given in combination with CsA, the mean graft survival times were prolonged to
      27.6+/-5.3 and 36.6+/-8.0 days, respectively (P<0.01). ACTH levels, adrenal
      weights, and thymic weights were not significantly different in the treatment and
      control groups receiving intestinal transplants. CONCLUSIONS: BUD enhances the
      immunosuppressive effects of CsA and prolongs small bowel allograft survival in
      rats without inhibiting normal ACTH release. These data suggest that BUD may be a
      useful immunosuppressive agent for clinical intestinal transplantation.

PMID- 9158014
TI  - Improvement of cardiac output and liver blood flow and reduction of pulmonary
      vascular resistance by intravenous infusion of L-arginine during the early
      reperfusion period in pig liver transplantation.
AB  - BACKGROUND: The release of liver arginase after orthotopic liver transplantation
      (OLT) causes a deficiency of L-arginine and nitrite in the plasma. This
      deficiency is possibly related to pulmonary hypertension and reduced hepatic
      blood flow, which are commonly observed in the immediate reperfusion period. The
      aim of this study was to evaluate the impact of L-arginine supplementation on
      metabolic and hemodynamic parameters during liver reperfusion after OLT in pigs.
      METHODS: Thirteen pig OLTs (control group, n=6; arginine group, n=7) were
      performed by a standard technique. Cold ischemic time was 20 hr. L-Arginine was
      infused at a dosage of 500 mg/kg body weight into the donor pigs (30 min before
      liver explantation) and also into the recipients (over a period of 3 hr from the
      beginning of the reperfusion period). At the end of the experimental study, the
      pigs were killed with an overdose of potassium. RESULTS: In the control group,
      liver revascularization increased plasma arginase concentrations (+615%) and
      reduced plasma levels of L-arginine (-87%), nitrite (-82%), and nitrate (-53%).
      Infusion of L-arginine increased plasma levels of L-arginine from 94+/-21
      micromol/L to 1674+/-252 micromol/L (P<0.001), L-ornithine from 46+/-8 micromol/L
      to 2215+/-465 micromol/L (P<0.001), and L-citrulline from 58+/-8 micromol/L to
      116+/-34 micromol/L (P<0.001), but had no effect on plasma levels of nitrite and
      nitrate. Administration of L-arginine in the donor pigs did not produce any
      systemic or organ-specific hemodynamic alterations. Infusion of L-arginine into
      the recipient pigs improved cardiac performance (increase in heart rate [+61%,
      P=0.017] and cardiac index [+53%, P=0.005], reduction in pulmonary capillary
      wedge pressure [-54%, P=0.014]). Moreover L-arginine infusion increased oxygen
      consumption (+65%, P=0.003), reduced pulmonary vascular resistance index
      (P=0.001), stimulated portal venous blood flow (P=0.014), and elevated body
      temperature during the reperfusion period (P=0.007). CONCLUSIONS: From these
      data, we conclude that the infusion of L-arginine during OLT improves the
      hemodynamic performance of the heart, lung, and liver.

PMID- 9158015
TI  - Efficacy of immunosuppressive drugs in islet xenotransplantation: leflunomide in
      combination with cyclosporine and mycophenolate mofetil prevents islet xenograft
      rejection in the pig-to-rat model.
AB  - BACKGROUND: Morphological characteristics of islet xenograft rejection differ
      from those of islet allograft rejection. Therefore, prevention of islet xenograft
      rejection probably requires a different type of immunosuppression from that used
      in allogeneic transplantation. METHODS: Fetal porcine islet-like cell clusters
      (ICC) were transplanted into the renal subcapsular space of rats treated with
      different immunosuppressive protocols. The existence of a cellular infiltrate or
      deposits of antibodies and complement in the grafts was evaluated at different
      times after transplantation using immunohistochemistry. RESULTS: Treatment with
      leflunomide (LEF), cyclosporine (CsA), mycophenolate mofetil (MMF), 15
      deoxyspergualin, and rapamycin alone or in combination had an insufficient
      inhibitory effect on ICC xenograft rejection. However, in animals treated with
      LEF+CsA, the rejection process was markedly inhibited. However, some macrophages
      and T cells were still present, and at 24 days, the xenografts were destroyed. In
      LEF+CsA-treated animals that were given sera containing an excessive amount of
      rat anti-porcine xenoreactive antibodies, marked deposits of IgG, and to some
      extent C3 as well, were detected along the border between intact ICC, and the
      xenografts were surrounded by macrophages. However, almost no cells infiltrated
      the grafts, and there were many intact ICC. In animals treated with LEF+CsA+MMF,
      only occasional infiltrating cells were seen at 12 and 24 days after
      transplantation, and the endocrine tissue was completely intact. CONCLUSIONS:
      LEF+CsA+MMF prevented rejection of porcine ICC xenografts in the rat for up to 24
      days after transplantation.

PMID- 9158016
TI  - Murine OKT4A immunosuppression in cadaver donor renal allograft recipients: a
      cooperative clinical trials in transplantation pilot study. Cooperative Clinical
      Trials in Transplantation Research Group.
AB  - BACKGROUND: A phase I study of anti-CD4 immunosuppression of cadaver donor renal
      allograft recipients was conducted by the NIH Cooperative Clinical Trials in
      Transplantation to assess safety, tolerability, immunoactivity, and
      pharmacokinetics of multiple infusions of murine anti-human CD4 monoclonal
      antibody OKT4A. METHODS: Thirty patients were enrolled (from August 1992 to
      October 1993) and received OKT4A at doses of 0.5 mg/kg (24 patients), 1.0 mg/kg
      (three patients), and 2.0 mg/kg (three patients) beginning and continuing for 12
      consecutive days with a standard regimen of cyclosporine, azathioprine, and
      prednisone. OKT4A treatment was continued postoperatively if serum creatinine 24
      hr after transplantation was <85% of pretransplantation baseline creatinine.
      RESULTS: Ninety-three percent of patients treated at 0.5 mg/kg OKT4A and all
      patients at higher doses had mean peak CD4 saturations in excess of 90%. A human
      antimouse antibody response of more than three times pretreatment levels was
      observed in 84% of patients. There was no evidence of CD4 T-cell depletion. OKT4A
      was well tolerated without first-dose side effects. For the 19 eligible patients
      treated with 0.5 mg/kg OKT4A with initial graft function, the 3-month treated
      rejection rate was 37%. The 2-year graft survival rate for all 30 patients
      enrolled was 83%, and for the 19 eligible patients it was 95%. CONCLUSIONS: The
      high percentage of CD4 saturation, minimal side effects, the observation of a low
      3-month rejection rate, and an excellent 2-year graft survival rate in patients
      treated with 0.5 mg/kg OKT4A support the continued investigation of an anti-CD4
      approach to immunosuppressive therapy.

PMID- 9158017
TI  - Renal transplantation for patients with autoimmune diseases: single-center
      experience with 42 patients.
AB  - BACKGROUND: In patients with autoimmune diseases such as vasculitis or systemic
      lupus erythematosus (SLE), end-stage renal disease develops in a high percentage
      of patients, and kidney transplantation has become a therapeutic option. However,
      only limited data about the prognosis and outcome after kidney transplantation
      are available. METHODS: Long-term graft survival and graft function of renal
      transplant recipients with SLE, Wegener's granulomatosis, microscopic
      polyangiitis, Goodpasture's syndrome, and Henoch-Schonlein purpura were evaluated
      in a single center. In addition, the incidence of renal and extrarenal relapses
      and the impact of the immunosuppressive therapy on the course of the autoimmune
      disease were studied. RESULTS: Renal transplant recipients with autoimmune
      diseases such as vasculitis and SLE had a patient survival rate (94% after 5
      years) and a graft survival rate (65% after 5 years) comparable to those of
      patients with other causes of end-stage renal disease (patient survival 88% and
      graft survival 71% after 5 years). Graft losses due to the underlying disease
      were rare. Extrarenal relapses occurred in three patients with Wegener's
      granulomatosis, one patient with microscopic polyangiitis, and three patients
      with SLE, but were less frequent compared with the period with chronic dialysis
      therapy. Autoantibody levels in patients with SLE, Wegener's granulomatosis, or
      microscopic polyangiitis did not seem to influence the outcome. CONCLUSIONS:
      Renal transplantation should be offered to patients with autoimmune diseases.
      Follow-up should include the short-term control of renal and extrarenal disease
      activity.

PMID- 9158019
TI  - Risk factors for vascular thrombosis in pediatric renal transplantation: a
      special report of the North American Pediatric Renal Transplant Cooperative
      Study.
AB  - Vascular thrombosis remains a major cause of graft failure, accounting for 12.2%
      of failed index transplants and 19.2% of repeat transplants. We conducted a
      special study to identify the risk factors for vascular thrombosis. A total of
      4394 transplants (2060 living donor [LD] transplants and 2334 cadaver donor [CAD]
      source transplants) were evaluated. The respective vascular thrombosis rates for
      LD and CAD transplants were 38/2060 (1.8%) and 100/2334 (4.2%) (P<0.001).
      Univariate analysis showed that the rate of graft loss due to thrombosis was
      significantly higher in younger children (less than 2 years of age) as compared
      with older age groups (2-5 years, 6-12 years, and more than 12 years of age)
      (9.0% vs. 5.5%, 4.4%, and 3.5% for CAD transplant recipients and 3.5% vs. 3.4%,
      0.7%, and 1.9% for LD graft recipients). Recipients of kidneys from cadaver
      donors less than 5 years of age had a significantly higher thrombosis rate (8.3%)
      than did recipients from older donor groups (5-10 years, 4.5%; greater than 10
      years, 3.2%). Recipients of kidneys with cold ischemia time greater than 24 hr
      also had a higher thrombosis rate (5.6%), as compared with recipients of kidneys
      with a shorter cold ischemia time (3.2%). Recipients of antilymphocyte therapy on
      day 0 or day 1 were at dimished risk of graft loss due to thrombosis (2.2% vs.
      4.1%, P=0.001). Comparable trends were seen for both LD and CAD organ recipients.
      LD organ recipients with a history of prior transplantation had a significantly
      higher rate of thrombosis as compared with those who received a primary
      transplant (4.6% vs. 1.6%, P=0.005). For both LD and CAD organ recipients, the
      occurrence of acute tubular necrosis was a significnat risk factor for the
      development of thrombosis. Regression analysis showed that for LD organ
      recipients, a history of prior transplantation increased the risk for thrombosis,
      whereas increasing recipient age had a linear decreasing risk effect. The use of
      antilymphocyte antibody or cyclosporine on day 0/1 decreased the risk for
      thrombosis. For CAD kidney recipients, organ cold ischemia time greater than 24
      hr increased the risk for thrombosis. The use of antibody induction therapy,
      donors greater than 5 years of age, and increasing recipient age were factors
      that decreased the risk for thrombosis.

PMID- 9158018
TI  - Antilymphocyte induction therapy in cadaver renal transplantation: a
      retrospective, multicenter United Network for Organ Sharing Study.
AB  - Antilymphocyte induction therapy in cadaver renal transplantation is
      controversial. The effectiveness of antilymphocyte therapy in the current era of
      cyclosporine and tacrolimus use has been questioned. The United Network for Organ
      Sharing data set for the Center-Specific Outcomes Analysis, which has been
      verified by the transplant centers, was used for this study. At the time
      information in the database was confirmed, all transplant centers were queried on
      their use of an antilymphocyte preparation at the time of transplantation, and
      whether it was used within 24 hr of transplant surgery, the duration of the
      specific reagent. This allowed us to analyze 24,191 cadaver transplant procedures
      performed between the October 1, 1987, and the January 31, 1991. Using Cox
      regression analysis, as well as semiparametric logistic regression models, we
      demonstrated improved allograft outcomes in patients who received either
      Minnesota antilymphocyte globulin for 5 days or more or OKT3 for 7 days or more.
      The relative risk was 0.82 for Minnesota antilymphocyte globulin and 0.86 for
      OKT3 (for both, P<0.001). Semiparametric models were then used to compare the
      effectiveness of the antilymphocyte preparation in both a patient with at least a
      three-antigen mismatch and patients who had a zero-antigen mismatch. The
      improvement in graft survival was seen in both match grades. These data
      demonstrate the improved outcomes with the use of antilymphocyte preparations
      during the early posttransplant period in the modern cyclosporine era.

PMID- 9158020
TI  - Long-term renal allograft survival: prognostic implication of the timing of acute
      rejection episodes.
AB  - BACKGROUND: The timing of an acute rejection may have a variable impact on renal
      allograft survival. To determine whether the time of first acute transplant
      rejection (ATR) is an independent predictor of long-term allograft survival, we
      studied 31,600 first cadaveric renal transplants that were functional on the
      first transplant anniversary, from 217 U.S. centers. METHODS: Transplant patients
      were divided into four groups according to the time to the first ATR: no
      rejection in year 1 (group I); predischarge ATR (group II); first ATR between
      discharge and month 6 (group III); and first ATR in months 7-12 (group IV).
      RESULTS: Four-year allograft survival after year 1, estimated by a Cox
      proportional hazard model adjusting for 19 cofactors, was 78%, 72%, 69%, and 54%
      for groups I-IV, respectively (P<0.0001 for each comparison to group I). In those
      patients who had ATR episodes in more than one time period, later episodes were
      associated with worse long-term allograft survival, an observation that was
      independent of previous ATR episodes. CONCLUSIONS: We conclude that late
      occurrence of a first acute rejection portends a worse prognosis for allograft
      survival after the first year. Later rejections, in combination with previous
      rejections, also lead to worse long-term allograft survival. Unlike early ATRs
      occurring in the setting of supervised immunosuppression, late occurring ATR may
      reflect inadequate immunosuppression from noncompliant behavior or may reflect
      disruption or lack of immune tolerance to the allograft. Efforts to minimize late
      transplant loss require a combination of strategies directed at both immunologic
      and behavioral factors.

PMID- 9158021
TI  - Systemic vasculitis in a kidney transplant population.
AB  - BACKGROUND: Systemic vasculitis as original disease might adversely influence the
      result of kidney transplantation. METHODS: The clinical course after 32
      transplantations to 26 patients with microscopic polyangiitis, Wegener's
      granulomatosis, Henoch-Schonlein purpura, thrombotic thrombocytopenic
      purpura/hemolytic uremic syndrome, or Goodpasture's disease was evaluated. The
      median follow-up time was 82 months (range, 4-132 months). Frozen sera from 25
      transplantations were analyzed for Goodpasture antibodies, myeloperoxidase
      antineutrophil cytoplasmic antibodies (ANCA), and proteinase 3 ANCA. RESULTS:
      Survival of patients and grafts did not differ between patients and matched
      controls. Recurrent vasculitis occurred with seven grafts (four patients with
      microscopic polyangiitis or Wegener's granulomatosis, two patients with Henoch
      Schonlein purpura, and one patient thrombotic thrombocytopenic purpura). New
      onset hematuria was the initial renal symptom in five patients. Treatment with
      corticosteroids, cyclophosphamide, and/or plasma exchange was most often
      effective, but two grafts were lost. Proteinase 3 ANCA titers were increased to
      12-738 U/ml before seven transplants. The patient with the lowest titer lost his
      graft due to recurrence, two other patients had reversible recurrence after 1
      year and 5 years, two patients lost their grafts due to unknown/unrelated causes,
      and two patients' grafts remain without recurrence. Myeloperoxidase ANCA were
      increased to 22-39 U/ml before two transplants, which have been uneventful for 4
      years. CONCLUSIONS: An awareness of the small but perpetual risk of recurrence
      facilitates early treatment that may save the transplant. Testing for hematuria
      and early transplant biopsies, and possibly monitoring of ANCA titers, are
      essential, but pretransplant ANCA titers have no predictive value in asymptomatic
      patients. Results of kidney transplantation in patients with vasculitis are as
      good as in other patients.

PMID- 9158023
TI  - Renal disease in hepatitis C-positive liver transplant recipients.
AB  - Glomerular abnormalities are frequent in patients undergoing liver
      transplantation; however, renal dysfunction following transplantation is mainly
      attributed to cyclosporine toxicity. Membranoproliferative glomerulonephritis
      (MPGN) is seen in patients infected with hepatitis C virus (HCV), the virus
      responsible for 30% of the end-stage liver disease leading to liver
      transplantation. To determine the incidence of renal abnormalities in liver
      transplant recipients and the association with HCV, we undertook a longitudinal
      study in HCV-positive (n=91) and HCV-negative (n=106) liver transplant
      recipients. Mean creatinine clearance before transplantation was 94 ml/min/1.73
      m2 in HCV+ patients and 88 ml/min/1.73 m2 in HCV- patients. By 3 months after
      transplantation, the mean creatinine clearance decreased by approximately one
      third in both groups. A greater proportion of HCV+ patients excreted >2 g
      protein/day after transplantation (P=0.05) and had renal biopsies showing MPGN
      than did HCV- recipients (4/10 HCV+ patients vs. 0/7 HCV- patients; P=0.1). In
      the HCV+ group, proteinuria was not associated with recurrent HCV hepatitis, DQ
      matching, posttransplant diabetes, or hypertension. Treatment of HCV-related MPGN
      with interferon-alpha2b appeared to stabilize proteinuria and renal function but
      did not reverse renal dysfunction nor cause liver allograft rejection. After
      transplantation, HCV+ patients had similar renal function over 3 years after
      transplantation, compared with HCV- patients, but they had an increased risk of
      proteinuria and occurrence of MPGN that was only partially responsive to
      interferon.

PMID- 9158022
TI  - Clinical presentation and outcome of tuberculosis in kidney, liver, and heart
      transplant recipients in Spain. Spanish Transplantation Infection Study Group,
      GESITRA.
AB  - BACKGROUND: Tuberculosis is unusual in transplant recipients. The incidence,
      clinical manifestations, and optimal treatment of this disease in this population
      has not been adequately defined. The present study was undertaken to assess the
      incidence, clinical features, and response to therapy of Mycobacterium
      tuberculosis infection in solid-organ transplant recipients. METHODS: We
      evaluated retrospectively the incidence, clinical characteristics, diagnostic
      procedures, antituberculous treatment, clinical course, and factors influencing
      mortality in 51 solid-organ transplant recipients who developed tuberculosis
      after transplantation. We also reviewed the world literature on tuberculosis in
      solid-organ transplantation. RESULTS: The overall incidence of tuberculosis was
      0.8%. The localization was pulmonary in 63% of the cases, disseminated in 25%,
      and extrapulmonary in 12%. Tuberculosis developed from 15 days to 13 years after
      surgery (mean, 23 months). In one third of the cases, diagnosis was not suspected
      initially, and in three cases, diagnosis was made at necropsy. Fever was the most
      frequent symptom, followed by constitutional symptoms, cough, respiratory
      insufficiency, and pleuritic pain. Fifteen patients (33%) developed
      hepatotoxicity during treatment; hepatotoxicity was severe in seven cases.
      Hepatotoxicity was higher in patients receiving four or more antituberculous
      drugs (50%) than in patients receiving three drugs (21%; P=0.03). Serum levels of
      cyclosporine decreased in the 26 patients under the simultaneous use of rifampin.
      Nine of them (35%) developed acute rejection, and five (56%) died, in comparison
      with 3 of 17 patients (18%) who did not develop rejection after the use of
      cyclosporine and rifampin (P=0.03). Although microbiological response was
      favorable in 94% of the 35 patients who completed 6 or more months of treatment,
      16 other patients (31%) died before diagnosis or in the course of treatment. None
      of the patients treated for more than 9 months died as a consequence of
      tuberculosis, whereas the mortality rate was 33% among those treated for 6 to 9
      months (P=0.03). Use of antilymphocyte antibodies or high doses of steroids for
      acute rejection before tuberculosis was associated with a higher mortality rate.
      CONCLUSIONS: M tuberculosis causes serious and potentially life-threatening
      disease in solid-organ transplant recipients. Treatment with at least three drugs
      during 9 months or more, avoiding the use of rifampin, appears to be appropriate.

PMID- 9158024
TI  - Safe pancreas transplantation in patients with coronary artery disease.
AB  - BACKGROUND: This study was conducted to determine the risk of clinically
      significant posttransplant cardiac events (PCEs) in a cohort of diabetic patients
      referred for pancreas transplantation. METHODS: Between April 1991 and December
      1995, 316 insulin-dependent diabetics were evaluated for pancreas
      transplantation. Patients were assessed for risk factors for coronary artery
      disease (CAD), and underwent screening for significant CAD by a standardized
      algorithm that included selective coronary angiography. For the 3-year period
      following transplantation, PCEs were identified, and related to pretransplant
      cardiac risk factors. RESULTS: Only four patients (1.3%) were turned down for
      cardiac contraindications. Coronary angiography was done in 74 patients (27% of
      the active transplant candidates) during the evaluation period because of the
      patient's history or a positive stress test. Significant coronary artery stenoses
      were found in 54% of the patients catheterized. Twenty-five of these 40 patients
      (63%) underwent revascularization with percutaneous transluminal coronary
      angioplasty and/or coronary artery bypass grafting. A total of 359 organs were
      subsequently transplanted into 194 of these patients. No deaths occurred within
      30 days of any of the transplants; four percent of transplant recipients died of
      cardiac causes within the follow-up period (median 23 months). Those with no
      pretransplant evidence of CAD had significantly lower rates of PCE (2% and 8% at
      1 and 3 years, respectively) than those with pretransplant evidence of CAD (11%
      and 29% at 1 and 3 years, P<0.01; relative risk, 4.3). CONCLUSIONS: Routine
      cardiac screening of pancreas recipients with selective angiography and
      revascularization allows patients with significant CAD to safely undergo pancreas
      transplantation. Patients should rarely be excluded from pancreas transplantation
      for cardiac causes.

PMID- 9158025
TI  - Alloreactive delayed-type hypersensitivity in graft recipients: complexity of
      responses and divergence from acute rejection.
AB  - BACKGROUND: Immunocompetent allograft recipients typically exhibit evidence of
      sensitization to graft antigens through alloantibody production and allograft
      rejection, as well as delayed-type hypersensitivity (DTH) reactivity to donor
      antigens. Most previous studies have relied on whole donor splenocytes, which
      primarily elicit allorestricted allogeneic responses, to test specific DTH
      responses and overlook the independent element of self-restricted responses in
      host-allograft interactions. METHODS: We tested expression of self-MHC-restricted
      versus allo-MHC-restricted allogeneic DTH responses in both nonimmunosuppressed
      and tolerized C57BL/6 mice. Mice were sensitized for allogeneic DTH either by
      rejection of skin or cardiac allografts, or by subcutaneous injection of intact
      allogeneic splenocytes. Patterns of alloreactive DTH were compared in
      allosensitized, tolerant, and naive hosts. RESULTS: All three methods of
      allosensitization resulted in equivalent self-restricted and allorestricted
      allogeneic DTH responses in nonimmunosuppressed mice. Gallium nitrate blocked
      acute rejection of cardiac allografts, and also blocked allosensitization of both
      self-restricted and allorestricted DTH responses, but did not influence the
      expression of DTH responses in presensitized mice. Gallium nitrate treatment
      could not block acute rejection of skin allografts, but interfered with
      sensitization for self-restricted, but not allorestricted, DTH responses in these
      recipients. This divergence of self- versus allo-MHC-restricted allosensitization
      for DTH was observed in two additional situations: the rates of allosensitization
      for self-restricted versus allorestricted DTH, and the acquisition of
      allorestricted, but not self-restricted, alloreactive DTH responses in cardiac
      allograft tolerant mice subsequently challenged with a skin allograft.
      CONCLUSIONS: These studies demonstrate that acute rejection correlates generally
      with allogeneic DTH, whereas tolerance is associated with a lack of alloreactive
      DTH. However, self-restricted and allorestricted allosensitization can operate
      independently in allograft recipients. Thus, the relationships between
      alloreactive DTH and graft-induced allosensitization, acute rejection, or
      tolerance are more complicated than previously appreciated.

PMID- 9158027
TI  - Donor-specific cytokine production by graft-infiltrating lymphocytes induces and
      maintains graft vascular disease in human cardiac allografts.
AB  - BACKGROUND: The development of graft vascular disease (GVD) in the allograft is a
      major impediment for long-term survival of heart transplant recipients. GVD may
      be mediated by cellular processes, in response to the transplanted heart, and
      regulated by cytokines. METHODS: We studied donor-specific cytokine production
      patterns in graft-infiltrating lymphocyte cultures propagated from endomyocardial
      biopsies. The biopsies were derived from patients with and without signs of GVD,
      as diagnosed by angiography at 1 year after heart transplantation. RESULTS: In
      the first year after transplantation, significantly more T-helper (Th) 1
      cytokines (interleukin [IL]-2: P=0.04; interferon-gamma: P=0.01), but not Th2 (IL
      4 and IL-6) cytokines, were produced by cultures of patients with GVD compared
      with patients without GVD. Thereafter, the Th1 cytokine levels in patients with
      GVD normalized to the levels of patients without GVD. Detectable levels of IL-6
      were produced significantly more often (P=0.009) by cultures obtained more than 1
      year after transplantation from patients with GVD. CONCLUSIONS: The results
      suggest that high levels of Th1 cytokines produced by graft-infiltrating
      lymphocytes early after transplantation may be responsible for activation of
      vascular endothelium, leading to the migration and proliferation of smooth muscle
      cells that is characteristic of GVD. IL-6, produced later after transplantation,
      continues this process by promoting smooth muscle cell proliferation.

PMID- 9158026
TI  - Quantitative analysis of T helper 1, T helper 2, and inflammatory cytokine
      expression in patients after allogeneic bone marrow transplantation: relationship
      with the occurrence of acute graft-versus-host disease.
AB  - BACKGROUND: To further delineate the cytokine involvement in human acute graft
      versus-host disease (GVHD), we analyzed cytokine expression in peripheral blood
      mononuclear cells (PBMC) from patients who developed acute GVHD after allogeneic
      bone marrow transplantation and from those who did not. METHODS: We used a highly
      quantitative and sensitive polymerase chain reaction assay based on the
      coamplification of an internal standard, with the cDNA derived from the mRNA of
      interest. Results are expressed in copy numbers, after normalization to a fixed
      amount of actin, allowing comparison between different samples. After a
      myeloablative regimen, 22 patients with hematological diseases received an
      unmanipulated allograft from a matched sibling. They were subsequently submitted
      to prophylactic immunosuppression. We examined the transcription of genes
      encoding cytokines in PBMC and skin biopsies. We selected T helper 1 (interferon
      ([IFN]gamma, interleukin [IL]-2), T helper 2 (IL-4, IL-10), and inflammatory (IL
      1, IL-6) cytokines. RESULTS: Four weeks after bone marrow transplantation, the
      bulk of the PBMC population exhibited an increased expression of IL-1 and IL-6,
      with no major difference between GVHD+ and GVHD- patients. In addition, although
      IL-2 expression was not detected, increased levels of IFNgamma mRNA were observed
      in allografted patients, with higher levels in GVHD+ patients. In skin biopsies
      sampled at the beginning of GVHD, although low expression of IL-1 and IL-6 could
      be observed, neither type 1 (IL-2, IFNgamma) nor type 2 (IL-4, IL-10) cytokines
      could be detected. CONCLUSIONS: These studies suggest that the occurrence of
      human GVHD does not seem to be clearly associated with a T helper 1-type cytokine
      pattern.

PMID- 9158028
TI  - Human natural killer lymphocytes directly recognize evolutionarily conserved
      oligosaccharide ligands expressed by xenogeneic tissues.
AB  - BACKGROUND: In discordant xenogeneic species combinations, vascularized
      transplants are hyperacutely rejected, due to binding of xenoreactive natural
      antibodies (XNA) to selected tissues of the graft, followed by activation of the
      complement and coagulation cascades. A major epitope recognized by human XNA is
      the terminal disaccharide Gal alpha(1,3)Gal. Poorly defined, early cell-mediated
      events also contribute to recognition and rejection of discordant xenografts, and
      we have suggested a role of natural killer (NK) lymphocytes in this process.
      METHODS: Human NK cells were used as effectors in functional assays of adhesion
      to and lysis of xenogeneic discordant endothelial cells in vitro. Adhesion and
      lysis inhibition experiments were performed using a large panel of carbohydrates,
      as well as F(ab')2 fragments of human XNA. COS cells transduced with the porcine
      alpha-galactosyltransferase were also used as targets for NK cell adhesion.
      RESULTS: We demonstrate that XNA-reactive carbohydrate epitopes expressed by
      xenogeneic cells, including Gal alpha(1,3)Gal, are also directly recognized by
      human NK cells. First, selected carbohydrates in solution displace with
      comparable efficiency both XNA and NK cell binding to xenogeneic endothelium;
      second, XNA F(ab')2 fragments selectively inhibit human NK cell adhesion to
      porcine endothelium, but not to human endothelium; third, unstimulated NK
      lymphocytes adhere selectively to COS-7 cells expressing the porcine
      glycosyltransferase that encodes the Gal alpha(1,3)Gal epitope. CONCLUSIONS:
      Collectively, our findings suggest that humoral and cellular components of the
      natural immune response against heterologous species independently evolved
      recognition patterns directed against overlapping carbohydrate determinants.

PMID- 9158029
TI  - Human cell-mediated rejection of porcine xenografts in an immunodeficient mouse
      model.
AB  - BACKGROUND: In this study, we describe the development of a novel experimental
      system in which rejection of porcine skin grafts by human peripheral blood cells
      can be studied directly in vivo in immunodeficient mice. METHODS: To construct a
      small animal model of discordant xenograft rejection, recombinase-activating gene
      deficient mice (R-) lacking both mature B and T cells were grafted with porcine
      skin grafts and administered, by adoptive cell transfer, human cells stimulated
      in vitro with irradiated porcine peripheral blood cells to create Hu-R- mice.
      RESULTS: R- mice accepted porcine skin grafts indefinitely without the need for
      immunosuppression. In contrast, Hu-R- mice were able to reject porcine skin
      grafts. Immunohistochemical analysis of rejecting skin grafts revealed the
      accumulation of human T cells around dermal porcine vessels and focally in the
      epidermis. Graft rejection was manifested by vascular endothelial cell
      proliferation, edema at the dermal-epidermal border, and perivascular hemorrhage.
      The tissue damage observed in the rejecting grafts was similar to that observed
      in delayed primate anti-porcine cell-mediated rejection of vascularized organ
      xenografts. CONCLUSIONS: The development and characterization of a small animal
      model, to study cellular immune responses of human cells to discordant xenografts
      in vivo, should provide a convenient means for asking mechanistic questions
      related to discordant xenotransplantation, and may also provide a practical
      system for testing new approaches designed to prevent xenograft rejection.

PMID- 9158030
TI  - Split tolerance induced by immunotoxin in a rhesus kidney allograft model.
AB  - BACKGROUND: Renal allografts were performed in rhesus monkeys using FN18-CRM9, a
      potent immunotoxin capable of depleting T cells to less than 1% of baseline
      levels in blood and lymph nodes, as a preparative agent. We have recently
      reported that animals pretreated with FN18-CRM9 1 week before transplantation
      without further immunosuppression had prolonged graft survival time compared with
      control animals, and frequently became tolerant. METHODS: This report examines
      the alloimmune responses of recipient monkeys to the donor, including cytotoxic T
      lymphocyte precursor (CTLp) frequency, mixed lymphocyte response, and antidonor
      IgG response. RESULTS: CTLp frequencies declined significantly (P<0.01) after
      FN18-CRM9 treatment and renal transplantation. This decline in CTLp was initially
      nonspecific, as CTLp frequencies against third-party animals also declined
      (P<0.01). The decrease in CTLp was maintained in five of five animals tested 6
      months after transplant. However, unresponsiveness was limited to the CTL arm of
      the immune response as antidonor IgG was detected in four of four animals tested,
      and the 5-day mixed lymphocyte response stimulation index and relative response
      were not significantly different before and after transplant. In long-term
      survivors (>150 days), an increase in anti-third-party CTLp was detected 1 month
      after grafting with third-party skin. No change was seen in the antidonor CTLp
      frequency after donor skin grafting, indicating that a specific defect in the
      antidonor CTL response had developed. CONCLUSIONS: These data suggest that FN18
      CRM9 treatment of rhesus monkeys allows the development of specific down
      regulation of antidonor CTL activity in renal allograft recipients.

PMID- 9158031
TI  - Human leukocyte antigen compatibility in heart transplantation: evidence for a
      differential role of HLA matching on short- and medium-term patient survival.
AB  - BACKGROUND: Studies of the influence of human leukocyte antigen (HLA) matching on
      cardiac transplant outcome have proved inconclusive, mainly due to the lack of
      well-matched grafts. However, a growing number of studies report improved
      clinical course and patient survival in cases with increased HLA compatibility.
      Opelz et al. believe these benefits justify the introduction of prospective HLA
      matching strategies. METHODS: We performed univariate and multivariate analyses
      to examine the short- and medium-term influence of HLA matching on 556
      consecutive primary heart transplants performed at a single center between 1983
      and 1994. Overall graft survival at 1, 3, and 5 years was 80%, 74%, and 67%
      respectively. Sixteen (2.9%) grafts failed within 5 days and were not considered
      in the analysis of the HLA matching and graft survival data. RESULTS: Complete
      HLA-A, -B, and -DR typing data were available on 477 transplant pairs. The
      results demonstrate a 12% 1-year survival advantage for 31 patients with zero to
      two HLA antigen mismatches compared with three to six mismatches. The influence
      of each individual locus was 6.1%, 8.4%, and 5.4% for zero HLA-A, -B, and -DR
      mismatches, respectively, compared with two mismatches. However, when outcome
      from 1 to 5 years was considered, analysis of the role of each locus revealed
      marked differences. HLAA-matched grafts (n=45) had a 24% lower survival rate
      compared with two-antigen-mismatched grafts (n=148; 88% [SE 3.1] vs. 64% [SE
      8.2], respectively; P=0.009). Furthermore, 34% of HLA-A-matched grafts failed
      between 1 and 5 years, compared with only 5% of HLA-B-matched grafts (P=0.013).
      CONCLUSIONS: These data suggest that although HLA matching is effective at
      reducing acute graft loss, in the longer term, HLA-A matching may impair
      survival. HLA-A may serve as a restriction element for indirect presentation of
      allopeptides or tissue-specific minor histocompatibility antigens, facilitating
      chronic graft loss. Therefore, we advocate a differential role for HLA matching
      over two epochs. A blanket approach to prospective matching for heart transplants
      may be premature for optimal long-term survival.

PMID- 9158032
TI  - Clinical relevance of HLA-DPB locus matching for cadaver kidney retransplants: a
      report of the Collaborative Transplant Study.
AB  - BACKGROUND: Matching for the HLA class I loci A and B and for the HLA class II
      locus DRB is known to influence the survival rate of kidney transplants. It is
      unknown whether matching for the HLA class II locus DPB also exerts an influence
      on graft outcome. METHODS: The influence of matching for the HLA-DPB locus was
      analyzed based on DNA typing results obtained in more than 3600 first and 1300
      repeat cadaver kidney transplants. RESULTS: HLA-DPB mismatches had no deleterious
      influence on the outcome of first cadaver transplants. However, the influence was
      statistically significant for retransplants. One-year graft survival rates were
      83+/-2% with no mismatch (n=345), as compared with 76+/-2% with one mismatch
      (n=702, P=0.02), and 73+/-3% with two mismatches (n=258, P=0.003). The
      deleterious influence of HLA-DPB mismatches was particularly strong in
      retransplant recipients with >50% reactivity of preformed lymphocytotoxic
      antibodies, for which the 1-year graft survival rate was 70+/-4% with no
      mismatch, as compared with 69+/-3% with one mismatch (P=0.05) and 61+/-5% with
      two mismatches (P=0.003). CONCLUSIONS: These results indicate that HLA-DPB is a
      clinically relevant histocompatibility locus in cadaver kidney retransplantation.
      It is proposed that prospective typing and matching for HLA-DPB should be
      implemented for cadaver kidney retransplants.

PMID- 9158034
TI  - Extended donor criteria: use of cardiac allografts after carbon monoxide
      poisoning.
AB  - BACKGROUND: An increasing demand for cardiac allografts for the treatment of end
      stage cardiac failure has led to a shift in the traditional views about donor
      criteria. The use of allografts exposed to high concentrations of carbon monoxide
      is still under discussion. The current literature on this topic is contradictory.
      We describe our experience with orthotopic cardiac transplantation, using cardiac
      allografts after carbon monoxide poisoning. METHODS: Between March 13, 1989 and
      August 1, 1996, 770 orthotopic heart transplantations were performed in our
      center. Within this period, we accepted five cardiac allografts from brain-dead,
      carbon monoxide-poisoned donors. Donor history showed carbon monoxide
      intoxication in all cases. At the time of organ explantation, donor hemodynamic
      parameters were feeble in all patients. RESULTS: The postoperative course was
      uneventful in three of the five recipients. The overall 3-year survival rate in
      this small group is 40%. Induction therapy or rescue therapy with mono/polyclonal
      antibodies was not necessary. Myocardial right-ventricular biopsies did not show
      any specific signs of carbon monoxide poisoning. CONCLUSIONS: In our opinion,
      cardiac allografts from donors exposed to carbon monoxide can be transplanted
      successfully in infants and adults, if there are no signs of severe hemodynamic
      dysfunction in the presence of a normal central venous pressure and low-dose
      support with catecholamines and there are no electrocardiographic changes in
      combination with elevated transaminase. With extended donor criteria, the hearts
      of carbon monoxide-poisoned victims could increase the number of suitable organs
      and lower the death rate of patients on the United Network for Organ Sharing and
      Eurotransplant International Foundation waiting lists.

PMID- 9158033
TI  - Indefinite islet allograft survival in mice after a short course of treatment
      with anti-CD45 monoclonal antibodies.
AB  - BACKGROUND: Although islet cell transplantation is considered an ideal form of
      endocrine replacement for type I diabetes, clinical application in humans is
      still not feasible. New immunosuppressive strategies are clearly needed to
      control inexorable rejection. CD45 is a family of transmembrane protein tyrosine
      phosphatases critically involved in the regulation of lymphocyte activation
      signals. Anti-CD45RB monoclonal antibody can prevent rejection of murine renal
      allografts. METHODS: Here, we examine the consequences of targeting CD45 in
      murine islet cell transplantation. Diabetic mice recipients received islet
      allografts under the kidney capsule and were divided into seven groups.
      Recipients received no treatment (controls) or anti-CD45RB monoclonal antibody
      (mAb; MB23G2 or C363.16A) at different dosages and treatment intervals. RESULTS:
      All untreated control animals lost islet function, becoming hyperglycemic within
      10-17 days after transplantation. Animals treated with either anti-CD45RB mAb
      showed a significant prolongation of islet allograft survival when compared with
      controls. Anti-CD45RB MB23G2 at 100 microg/day, given on days -1, 0, and 5 was
      particularly effective, inducing indefinite islet allograft survival in 60% of
      recipients. CONCLUSIONS: These results indicate that anti-CD45 mAbs are potent
      immunomodulatory agents, able to sustain indefinite islet allograft function
      after a short treatment course in the highly immunogenic model of islet
      transplantation.

PMID- 9158035
TI  - Sarcomatoid renal cell carcinoma with widespread metastases to liver and bones in
      a kidney transplant recipient.
AB  - A case of sarcomatoid renal cell carcinoma with widespread metastases to liver
      and bones in a cadaver renal transplant recipient is reported in this article.
      The patient underwent a kidney transplant at the age of 43 and was treated with
      various immunosuppressive agents after surgery. Twelve months after the
      transplantation, multiple tumors were found in the liver, and the patient died 8
      months later. Pathological examination at autopsy revealed renal cell carcinoma
      with a sarcomatoid component in the right native kidney and metastases to liver
      and bones. It is unusual for renal cell carcinoma to undergo sarcomatous
      transformation and to metastasize to the liver before reaching other organs. We
      speculate that immunosuppressants may have altered malignant cell proliferation,
      invasion, and the form of metastasis in this case.

PMID- 9158036
TI  - Efficacy of quantitative analysis of Epstein-Barr virus-infected peripheral blood
      lymphocytes by in situ hybridization of EBER1 after living-related liver
      transplantation: a case report.
AB  - BACKGROUND: We describe a 1-year-old female who underwent living-related liver
      transplantation for biliary atresia and developed Epstein-Barr virus (EBV)
      related posttransplant lymphoproliferative disorder. This disorder was resolved
      after withdrawal of immunosuppression therapy and administration of a high dose
      of acyclovir. METHODS: To quantify the extent of EBV activation and EBV load in
      peripheral blood, we measured the levels of EBV-infected peripheral lymphocytes
      by in situ hybridization (ISH) of EBV-encoded small mRNA 1 (EBER1). RESULTS: The
      decline in the number of EBER1-positive lymphocytes (from 362/50,000 mononuclear
      cells to 0/50,000) after treatment was in accord with the patient's clinical
      improvement. CONCLUSIONS: This finding showed that quantitative analysis of EBV
      infected peripheral lymphocytes by ISH of EBER1 is very useful for monitoring the
      EBV load and response to treatment of patients with EBV-related disorders.
      Furthermore, ISH may become an important tool for the early diagnosis and
      prevention of life-threatening posttransplant lymphoproliferative disorder in
      posttransplant patients.

PMID- 9158037
TI  - Human cytomegalovirus does not induce human leukocyte antigen class II expression
      on arterial endothelial cells.
AB  - Human cytomegalovirus (CMV) has been associated with allograft rejection and, in
      particular, with transplant-associated arteriosclerosis. However, the role CMV
      plays in the development of transplant-associated arteriosclerosis remains
      unclear. CMV can infect the endothelium, the interface between allograft tissue
      and the host immune cells, but the direct induction of endothelial human
      leukocyte antigen (HLA) class II by CMV remains controversial. Our previous
      studies with venous endothelial cells (EC) have shown that CMV does not directly
      induce this antigen on infected EC and, furthermore, renders these cells
      refractory to interferon (IFN)-gamma induction. However, questions have arisen
      regarding the relevance of these findings to arterial endothelia. Thus, we have
      extended these studies to determine whether similar interactions occur in
      arterial EC. EC derived from human coronary artery, aorta, and umbilical artery
      were assayed by immunofluorescence flow cytometry and dual immunohistochemical
      staining following IFN-gamma treatment and/or inoculation with CMV. Data
      generated by these experiments demonstrate that regardless of vascular origin:
      (1) CMV does not directly induce endothelial surface or cytoplasmic HLA class II,
      and (2) although uninfected arterial EC are HLA class II inducible by IFN-gamma,
      infected cells are completely refractory to this effect. These results suggest
      that CMV-mediated inhibition of HLA class II expression is a phenomenon shared by
      human arterial and venous endothelia of both fetal and adult origin.

PMID- 9158038
TI  - Pneumocystis carinii pneumonia after renal transplantation.

PMID- 9158039
TI  - Urate oxidase in hyperuricemic heart transplant recipients treated with
      azathioprine.

PMID- 9158040
TI  - Experimental evaluation of rodent exclusion methods to reduce hantavirus
      transmission to humans in rural housing.
AB  - An experimental assessment of methods to reduce rodent infestations in rural
      housing was conducted in Yosemite National Park, California, Sequoia/Kings Canyon
      National Parks, California, and Shenandoah National Park, Virginia. During
      pretreatment surveys, nearly all (63 of 68) selected units had past or ongoing
      rodent activity inside. Active infestations were found in 58.8% of the units.
      Peromyscus spp. represented 91.2% of all animals caught inside housing units.
      Despite little harborage, rodent activity was common near housing (290
      animals/2,254 trap nights). The most common species present was Peromyscus
      maniculatus (43-50% of all captures). This species was especially frequent (49
      87% of Peromyscus captures) around the foundations of housing units. Habitat had
      little effect on captures. There were 1.8 Peromyscus caught per unit along the
      foundations of housing in modified rural settings with grass lawns compared with
      1.2 Peromyscus caught per unit in sites located in mature woodlands. During
      autumn of 1994, randomly selected housing units were rodent proofed by sealing
      openings associated with chases, roof eaves, and attics with insulation and wire
      mesh. Housing was examined and the fauna was resampled in the spring-summer of
      1995. Rodent-proofed houses were infested significantly less often (3 of 28) than
      control houses (13 of 36) (P = 0.02) and the intensity of infestation was lower
      in experimental houses (6 versus 23 mice/treatment). More than 25% of the mice
      trapped inside the houses had been marked outside the houses during the three-day
      surveys, demonstrating movement of mice adjacent to the buildings into not rodent
      proofed housing. As in the previous autumn, most of the animals captured in
      (98.9%) and along the foundations of the houses (77.5%) were Peromyscus spp.
      These results demonstrate that Peromyscus frequently invade rural housing but
      rodent-proofing effectively eliminates or substantially reduces rodent activity.

PMID- 9158041
TI  - Cryptosporidium parvum in children with diarrhea in Zulia State, Venezuela.
AB  - The prevalence and importance of Cryptosporidium parvum as a causal agent of
      acute diarrhea among pediatric patients from Zulia State, Venezuela was assessed.
      Single stool specimens were collected from 310 children 0-60 months of age with
      acute diarrheal disease who were admitted to three public hospitals and from 150
      comparable control children without gastrointestinal symptoms who were seen as
      outpatients. Cryptosporidium parvum oocysts were identified in 35 (11.2%) of 310
      children with diarrhea and the coccidium was the single detectable pathogen in
      only 12 (34.2%). Other potential pathogenic parasites were present in most of the
      patients shedding oocysts (23 of 35, 65%). In nondiarrheal control children,
      oocysts were identified in nine (6%) of 150. The data suggest that C. parvum is
      relatively highly endemic in children 0-60 months of age in Zulia State and that
      although C. parvum may be an important pathogen associated with diarrhea, it may
      be a cause of only a small proportion of diarrheal episodes.

PMID- 9158042
TI  - Epidemiologic survey of Blastocystis hominis infection in Japan.
AB  - The incidence of Blastocystis hominis in a healthy population was determined by
      fecal examination of 6,422 Japanese and 54 resident non-Japanese who visited the
      St. Luke's International Hospital Health Screening Center for a routine medical
      check-up during a one-year period. Of the enrolled subjects, 30 Japanese (0.5%)
      and four non-Japanese (7.4%) had B. hominis in their stools. These individuals
      were asymptomatic except for one who reported flatus and one who reported mild
      abdominal discomfort. Statistical analysis indicated that the prevalence in the
      Japanese was lower than in the non-Japanese, and lower than the prevalence
      reported for other countries. Colonoscopic observations on seven B. hominis
      positive individuals did not reveal pathogenic intestinal lesions. Several months
      after the first examination, 23 of the B. hominis-positive individuals, including
      three non-Japanese, were re-examined. Although they had not been treated with
      anti-B. hominis drugs, 10 individuals were now B. hominis-negative (by stool
      examination) and eight were passing fewer organisms. The remaining five
      individuals were still discharging large numbers of B. hominis. These B. hominis
      positive individuals had no reported symptoms despite passing numerous organisms.
      Therefore, it seems that infection with B. hominis rarely gives rise to clinical
      symptoms. In no instance was invasion of host tissues by the organisms detected.

PMID- 9158043
TI  - A clinical study of brucellosis in adults in the Asir region of southern Saudi
      Arabia.
AB  - One hundred four Saudi patients with brucellosis who were admitted to Abha
      General Hospital in the Asir region of southern Saudi Arabia were studied. All
      the patients had Brucella melitensis infection; 61.5% were females while 38.5%
      were males. Their mean age was 32 years. Most of the patients (61.5%) lived in
      the lowland (Tihama) and the majority were shepherds (84.6%). The most common
      presenting symptoms were fever (100%), sweating (96.2%), headache (76.9%), joint
      pains (76.9%), and backache (73.1%). Physical findings included fever (96.2%),
      hepatomegaly (46.2%), splenomegaly (42.3%), tenderness over the spine (30.8%),
      arthritis (26.9%), and lymphadenopathy (19.2%). Mild anemia, leukopenia, and
      relative lymphocytosis were common. A history of raw milk ingestion was an
      important factor in disease transmission (84.6%), followed by close animal
      contact (73%) and raw liver consumption (63.3%). The study shows the
      effectiveness of several drug combinations in the treatment of brucellosis and
      the low relapse rate if the treatment is prolonged for not less than six weeks.

PMID- 9158044
TI  - Seasonality, malaria, and impact of prophylaxis in a West African village I.
      Effect of anemia in pregnancy.
AB  - The importance of malaria as a cause of anemia in pregnancy in endemic areas
      remains controversial. The prevalence of anemia in pregnant women following the
      dry (May) and the rainy (November) seasons was compared in two successive years
      in Bougoula village (region of Sikasso, Mali). Phase I (1992) was observational
      and included 172 pregnant women and 208 controls. In Phase II (1993, 174 pregnant
      women and 206 controls), malaria prophylaxis with proguanil (200 mg/day) and
      chloroquine (300 mg/week) was offered to pregnant women. A strong seasonal
      variation in the prevalence of moderate to severe anemia in pregnant women
      (hematocrit < 30%) occurred in Phase I (dry season = 8.7%, rainy season = 41.2%).
      This variation was present only in women of parity lower than five, and
      paralleled variation in parasitemia. In Phase II, the seasonal variation of
      anemia was suppressed in women under malaria prophylaxis (presence of
      antimalarial metabolites in urine), and the overall prevalence of moderate to
      severe anemia in pregnancy decreased by 55.5% (22.8-74.3%). We conclude that
      malaria is the major cause of anemia in pregnancy in this region. A high priority
      should be given to prevention of malaria in pregnancy.

PMID- 9158045
TI  - Seasonality, malaria, and impact of prophylaxis in a West African village. II.
      Effect on birthweight.
AB  - The impact of malaria on low birthweight was investigated in Bougoula village
      (Sikasso region, Mali). In two successive years, pregnant women were followed
      until delivery. Phase I (1992) was observational, with 135 complete observations.
      Phase II (1993) included 126 participants, who were offered malaria prophylaxis
      with proguanil (200 mg/day) and chloroquine (300 mg/week). The results show that
      1) infants of first and second pregnancies had lower birth weights (-382.7 +/-
      62.6 g; P < 0.0001) compared with higher rank pregnancies; 2) strong seasonal
      variation in birthweight was observed in Phase I, with an annual cycle, a nadir
      in January, and an amplitude of 372.4 g (P = 0.0002); 3) parasitemia measured
      during pregnancy was associated with lower birthweight in infants from first and
      second pregnancies, but not from higher parity mothers; and 4) malaria
      prophylaxis taken for 20 weeks or more in Phase II suppressed the seasonal
      variation of birthweight and the effect of low parity (+423.4 +/- 118.8 g; P =
      0.0004). We conclude that malaria in pregnancy has an important negative impact
      on birthweight in first and second pregnancies. Prophylaxis with proguanil and
      chloroquine is an effective prophylaxis when taken for 20 weeks or more.

PMID- 9158046
TI  - Arteether: risks of two-week administration in Macaca mulatta.
AB  - Male rhesus monkeys (Macaca mulatta) were administered daily doses of the
      antimalarial drug arteether. The 14-day treated group received either 24
      mg/kg/day, 16 mg/kg/day, or 8 mg/kg/day. The seven-day treatment group received
      either 24 mg/kg/day or 8 mg/kg/day. All control cases in each group received the
      sesame oil vehicle alone. Neurologic signs were absent for animals in the seven
      and 14-day treatment groups except for one monkey which showed diffuse
      piloerection on day 14, and another monkey receiving 24 mg/kg/day for seven days
      showed mild lethargy after the fourth day. Mild, sporadic anorexia was noted in
      all animals by day 14, and a single animal showed diffuse piloerection on day 14.
      Surgical anesthesia preceded killing by exsanguination and was accompanied by
      perfusion fixation of the central nervous system. Brain sections were cut and
      then stained for study by light microscopy. Evidence of neuronal pathology, both
      descriptive and numerical, was collected. The neuroanatomic and neuropathologic
      findings demonstrated that arteether produced extensive brainstem injury when
      administered for 14 days. The magnitude of brainstem neurotoxicity was dose
      dependent, where injury was greatest at the 24 mg/kg/day dose level, less at the
      16 mg/kg/day dose level, and least at the 8 mg/kg/day dose level. Arteether
      induced multiple systems injury to brainstem nuclei of 1) the reticular formation
      (cranial and caudal pontine nuclei, and medullary gigantocellular and
      paragigantocellular nuclei); 2) the vestibular system (medial, descending,
      superior, and lateral nuclei); and 3) the auditory system (superior olivary
      nuclear complex and trapezoid nuclear complex). The vestibular nuclei and the
      reticular formation were most severely injured, with the auditory system affected
      less. The cranial nerve nuclei (somatic and splanchnic) appeared to escape
      damage, with the exception of the abducens nerve nucleus. The same brainstem
      nuclear groups of seven-day treated monkeys appeared normal. The statistical data
      are concordant with the descriptive data in demonstrating neurotoxic effects. In
      summary, no neurologic deficits were detected in any of the vehicle control
      monkeys (14-day and seven-day cases). Monkeys in the 14-day treatment group were
      free of clinical neurologic signs throughout the first week. At day 14, fine
      horizontal nystagmus was seen in one monkey, and another monkey exhibited diffuse
      piloerection. Monkeys in the seven-day treatment group were free of clinical
      neurologic signs except for one case. This monkey was treated with 24/mg/kg/day
      of arteether and exhibited lethargy after the fourth day. These indications of
      dysfunction arose too late to be practical indicators of neurotoxicity.

PMID- 9158047
TI  - Supportive pentoxifylline in falciparum malaria: no effect on tumor necrosis
      factor alpha levels or clinical outcome: a prospective, randomized, placebo
      controlled study.
AB  - Pentoxifylline (POF) may suppress overproduction of tumor necrosis factor alpha
      (TNF alpha), which is thought to contribute to complications of human falciparum
      malaria. However, POF is believed to improve impaired capillary blood flow, which
      can be impaired in falciparum malaria. To test whether POF affects TNF alpha
      serum levels or other variables in this disease, we administered POF (20
      mg/kg/day intravenously in 150 ml of saline for five days) randomized versus
      placebo (150 ml of saline without POF) in addition to standard antimalarial
      therapy. After recruitment of 51 patients with Plasmodium falciparum malaria,
      those receiving POF had more nausea and abdominal discomfort than the placebo
      group, as expected. Eleven of 27 patients receiving POF and three of 24 patients
      receiving placebo requested termination of the study medication (P < 0.05).
      Pentoxifylline did not change the decrease of TNF alpha levels or affect the
      clinical course in a significant way. Since POF failed to improve the clinical
      situation or to impact numerous laboratory parameters (including TNF alpha,
      thrombin-antithrombin III, thrombomodulin, and human neutrophil elastase), the
      study was terminated earlier than planned. While this study does not specifically
      address cerebral complications of malaria, the results suggest that POF is not
      useful as a routine adjunct to the standard therapy of falciparum malaria.

PMID- 9158048
TI  - Praziquantel in the treatment of Schistosoma mansoni infection: comparison of 40
      and 60 mg/kg bodyweight regimens.
AB  - Two different regimens of praziquantel, 40 mg/kg in a single dose and 60 mg/kg in
      two divided doses administered 6 hr apart, for the treatment of Schistosoma
      mansoni infection were compared in Abu Homos, Egypt. Participants in this study
      included 1,588 subjects of both sexes between five and 50 years old from two
      rural communities; 730 from Farshout and 858 from Om El-Laban. The prevalence of
      S. mansoni infection was 57.9% in Farshout and 69.0% in Om El-Laban. Infected
      subjects received 60 mg/kg of praziquantel in two divided doses 6 hr apart at
      Farshout and 40 mg/kg in a single dose at Om El-Laban. Eight to ten weeks after
      treatment, three stool samples were collected from each treated subject on three
      consecutive days and evaluated quantitatively by the modified Kato technique. The
      failure rate was significantly higher at Om El-Laban than at Farshout (14.5%
      versus 4.1% (odds ratio [OR] = 3.95, P < 0.0001). A significantly higher failure
      rate was consistent after adjustment for age and number of excreted S. mansoni
      eggs per gram of feces before treatment (OR = 3.75, P < 0.0001). In spite of
      differences among cure rates between the two regimens, we recommend 60 mg/kg on
      an individual basis but not for population treatment, since administration of a
      single dose of a drug is more practical than two doses given 6 hr apart.

PMID- 9158049
TI  - Detection of circulating antigen by monoclonal antibodies for immunodiagnosis of
      angiostrongyliasis.
AB  - Two monoclonal antibodies, which recognize the epitope on an antigen with a
      molecular weight of 204 kD from the fifth-stage worm of Angiostrongylus
      cantonensis, were previously prepared and used to detect circulating antigens in
      patients with eosinophilic meningitis or meningoencephalitis and in mice
      experimentally infected with this parasite by a double-antibody, sandwich enzyme
      linked immunosorbent assay (ELISA). The levels of this circulating antigen in
      experimentally infected mice were significantly higher three weeks after
      infection. The ELISA values in the detection of circulating antigens in
      cerebrospinal fluid (CSF) from patients were markedly higher than those in serum.
      Immunodiagnosis of patients with angiostrongyliasis by this technique proved to
      be highly specific for circulating antigens in serum and CSF specimens; however,
      the sensitivity in CSF was significantly higher than in serum.

PMID- 9158050
TI  - Monoclonal antibodies to Paragonimus heterotremus and their potential for
      diagnosis of paragonimiasis.
AB  - Monoclonal antibodies (MAbs) specific to the lung fluke (Paragonimus
      heterotremus) were produced against the soluble metabolic products (excretory
      secretory antigen). Three hybrids secreting MAbs specific for P. heterotremus
      antigens were identified by an indirect enzyme-linked immunosorbent assay (ELISA)
      against a panel of homologous and 24 heterologous parasite antigens and
      Mycobacterium tuberculosis. Of the three specific clones, clone 10F2, which was
      IgG1 producing and which gave immune complex bands with 31.5-kD and 22-kD
      polypeptides by gel electrophoresis and immunoblotting, was selected for further
      characterization and evaluation of its possible diagnostic potential. The result
      obtained from an indirect immunofluorescent antibody test suggested that MAb 10F2
      reacted with mucosa and contents of the worm's intestine. The antibody could be
      readily used to prepare an affinity-purified antigen for use in an indirect ELISA
      that was highly sensitive and specific for the detection of circulating antibody
      in sera of paragonimiasis patients.

PMID- 9158051
TI  - Diagnostic value of an antibody enzyme-linked immunosorbent assay using affinity
      purified antigen in an area endemic for melioidosis.
AB  - Melioidosis, an infection caused by Burkholderia pseudomallei, is endemic in
      southeast Asia. The septicemic form of melioidosis is the leading cause of death
      from nonhospital-acquired septicemia in the northeastern part of Thailand. A
      major factor that contributes to the high mortality is the delay in isolation and
      identification of the causative organism. The present study was undertaken to
      evaluate the use of enzyme-linked immunosorbent assays based on an immunoaffinity
      purified antigen for detecting specific IgG and IgM antibodies to this organism
      as a rapid serodiagnostic method for melioidosis. The diagnostic value of these
      tests was evaluated in an actual clinical situation in an area endemic for
      melioidosis. The specificity of specific IgG test (82.5%) and the specific IgM
      test (81.8%) were significantly better than that of the indirect hemagglutination
      (IHA) test (74.7%). The sensitivity of the specific IgG assay (85.7%) was higher
      than that of the IHA test (71.0%) and the specific IgM test (63.5%). Specific IgG
      antibody was detected in a majority of septicemic melioidosis (87.8%), as well as
      in localized forms (82.6%). The specific IgG test was also better than the
      specific IgM test and the IHA test in identifying acute melioidosis cases in the
      first five days after admission. In addition, the IgG antibody level to this
      antigen remained high over a period of more than five years in those who had
      recovered from melioidosis and remained clinically free of the disease. These
      results indicate that the detection of specific IgG antibody is clinically useful
      for the diagnosis of acute melioidosis in an endemic area.

PMID- 9158052
TI  - Rapid diagnosis of dengue viremia by reverse transcriptase-polymerase chain
      reaction using 3'-noncoding region universal primers.
AB  - A reverse transcriptase-polymerase chain reaction (RT-PCR) method was developed
      as a rapid diagnostic test of dengue viremia. To detect dengue viruses in serum
      or plasma specimens, a pair of universal primers was designed for use in the RT
      PCR. Using these primers, the 3'-noncoding region of dengue virus types 1, 2, 3,
      and 4 could be amplified, but not those of other flaviviruses, such as West Nile
      virus, Japanese encephalitis virus, and yellow fever virus, or the alphavirus
      Sindbis virus. The sensitivity of the RT-PCR assay was similar to that of a
      quantitative fluorescent focus assay of dengue viruses in cell culture. Combining
      a silica method for RNA isolation and RT-PCR dengue virus could be detected in a
      6-hr assay. In a preliminary study using this method, we detected dengue virus in
      38 of 39 plasma specimens from which dengue virus had been isolated by mosquito
      inoculation. We then applied this method for detecting dengue viremia to 117
      plasma samples from 62 children with acute febrile illnesses in a dengue-endemic
      area. We detected dengue viremia in 19 of 20 samples obtained on the day of
      presentation, which had been confirmed as acute dengue infection by mosquito
      inoculation and antibody responses. The overall sensitivity of this method was
      91.4% (32 of 35; 95% confidence interval [CI] = 82.2-100%). The results from
      testing plasma samples from febrile nondengue patients showed a specificity of
      95.4% (42 of 44; 95% CI = 89.3-100%).

PMID- 9158054
TI  - Evidence that recurrent Plasmodium falciparum infection is caused by
      recrudescence of resistant parasites.
AB  - Isolates of Plasmodium falciparum obtained from 12 children attending different
      health facilities in the Madang Province, Papua New Guinea were typed for allelic
      variants of merozoite surface protein-1 and merozoite surface protein-2. Blood
      was obtained just before treatment with either amodiaquine or chloroquine and at
      intervals following treatment. All patients examined were found to be infected
      with genetically different parasites. Nine of the children were found to have
      single infections while three had mixed infections. In all patients, parasites
      reappearing in the blood following treatment had the same genotype as parasites
      in the primary infection. These results indicate that parasites reappearing in
      the blood following treatment were the result of true recrudescence and not new
      infections.

PMID- 9158053
TI  - Humoral response to defined Plasmodium falciparum antigens in cerebral and
      uncomplicated malaria and their relationship to parasite genotype.
AB  - The prevalence and concentration of IgG antibodies to defined Plasmodium
      falciparum antigens were assessed in serum samples of 97 children with cerebral
      malaria and 146 children with uncomplicated malaria. The antigens used included
      the schizont extract, ring-infected erythrocyte surface antigen, the C-terminal
      region of merozoite surface antigen-1 (MSA-1) (BVp42), and three recombinant
      proteins of MSA-2 (FC27, 3D7, and d3D7). Parasite isolates from 24 children with
      cerebral malaria and 22 children with uncomplicated malaria were genotyped for
      MSA-1 and MSA-2. The distribution of parasite genotypes belonging to the
      different allelic families was similar in both the cerebral and uncomplicated
      malaria groups. There were higher antibody levels to antigens derived from the
      infecting parasite genotype than to heterologous genotypes, but this difference
      was only statistically significant for antibody against the d3D7 antigen among
      children infected with the 3D7 parasite genotype (mean log = 4.72 versus 3.45
      antibody units [AU]; P = 0.029). Those who died were more likely to be infected
      with the FC27 genotype and had lower antibody levels to MSA-2 of the 3D7 type
      than had cerebral malaria patients who survived (mean log = 2.94 versus 3.79 AU;
      P = 0.049). Antibodies against parasites of the 3D7 genotype are associated with
      a better prognosis among children with cerebral malaria partly because these
      children are more likely to be infected with parasites of this genotype rather
      than the FC27 genotype, which appears to be more virulent.

PMID- 9158055
TI  - Lack of malaria parasite transmission between apes and humans in Gabon.
AB  - The International Center for Medical Research (CIRMF) is located in an area
      highly endemic for malaria in southeastern Gabon, where humans and apes (gorillas
      and chimpanzees) are living in the same geographic area. The presence of the
      CIRMF primate center housing apes (59 chimpanzees and nine gorillas in 1994)
      within the city of Franceville provided an opportunity to investigate the
      capability of cross-transmission of malaria species from humans to apes. The main
      vector of human malaria, Anopheles gambiae, was found in the primate center and
      in a nearby populated area of Franceville. Despite high malaria transmission in
      humans of both Plasmodium falciparum and P. malariae (mean of 43% cumulative
      prevalence in schoolchildren), none of the apes were found infected with
      plasmodia during a six-month investigation. However, low antibody levels against
      sporozoite and blood stages of both P. falciparum and P. malariae were detected
      in a few chimpanzees and gorillas. These results demonstrate that only rarely
      would apes be bitten in the field by mosquitoes infected with human malaria
      parasites. In the case of infection proven by serology, we did not find any
      evidence that blood-stage malaria parasites were able to the gametocyte stage.
      The absence of any established malaria transmission cycle within the primate
      colony of CIRMF indicates that apes cannot be considered as animal reservoirs for
      human malaria parasites in this environment.

PMID- 9158056
TI  - A genetic study of a melanization response to Sephadex beads in Plasmodium
      refractory and -susceptible strains of Anopheles gambiae.
AB  - A previously selected Plasmodium-refractory strain of Anopheles gambiae
      melanotically encapsulates many species of Plasmodium. Genetic studies of this
      strain have shown that this refractory phenotype is controlled by a limited
      number of genes, and the existence of two such genes, Pif-B and Pif-C, has been
      demonstrated. Further work to determine the molecular basis for this mode of
      refractoriness led to the discovery that the host-parasite interaction is
      mimicked by the mosquito's response to carboxymethyl (CM)-Sephadex beads injected
      into the thorax. These small beads are melanized within 24 hr in refractory
      mosquitoes but are rarely melanized in susceptible ones. Because of the
      considerable potential in using bead melanization as a model for Plasmodium
      refractoriness, we performed a genetic analysis of the differential response to
      beads. Reciprocal crosses of susceptible (4arr) and refractory (L35) mosquitoes
      and an analysis of F1 phenotypes were done. The F1 progeny had a phenotype
      similar to that of the parental refractory mosquitoes; therefore, dominant
      refractory allele(s) must be present in the refractory strain. Males from the
      reciprocal crosses had identical phenotypes, indicating that X-linked loci did
      not have a visible effect on the melanizing phenotype. To further study the mode
      of inheritance of the melanizing trait, a backcross of F1 females to 4arr males
      was done. The phenotypic distribution of the backcross progeny was bimodal, and
      the melanization phenotypes were similar to those of the susceptible and
      refractory parents. These data suggest that a small number of loci are
      responsible for the differential response to CM-Sephadex beads, and that one
      chromosomal region contributes strongly to the melanizing trait. Because the 4arr
      strain carries mutations in the pink eye (X) and red eye (III) genes, possible
      linkage of the melanizing phenotype to these two genes was tested. No linkage
      with either marker was detected. The pattern of inheritance of the melanizing
      phenotype is similar to that of the refractory phenotype of Pif-B; therefore, the
      genetic basis of the two responses may be the same.

PMID- 9158057
TI  - Subcutaneous dirofilariasis: single inoculum, multiple worms.
AB  - The present report describes an unusual case of subcutaneous dirofilariasis
      attributed to Dirofilaria repens. The patient, a 42-year-old caucasian male, who
      acquired the infection in Africa, presented on two different occasions, 10 months
      apart, with a sudden onset of symptoms and a living worm moving about in the
      periorbital tissues. Both worms were mature nongravid females. Based on the
      maturation of the respective reproductive systems and the volume and distribution
      of eggs in the reproductive tracts, it was concluded that both worms were in the
      same infecting inoculum. The first worm was at least two years old and the second
      was therefore 10 months older than the first. These observations indicate that
      the worms developed and resided in the tissues without eliciting any host
      response for two and three years.

PMID- 9158058
TI  - Inheritance of larval resistance to permethrin in Aedes aegypti and association
      with sex ratio distortion and life history variation.
AB  - The genetic mechanisms that confer larval permethrin resistance were investigated
      in two strains of Aedes aegypti, vectors of yellow fever and dengue hemorrhagic
      fever. Larval resistance to permethrin in an Ae. aegypti field-collected
      resistant Couva (R) strain was associated with the sex-determining locus by
      analysis of backcrosses to the susceptible Rockefeller (S) strain. The median
      lethal concentrations (LC50s) of these strains were 23.1 (95% confidence interval
      = 22.0-24.3) and 2.2 (2.0-2.3) parts/billion of permethrin, respectively. The
      estimated resistance ratio (RR) for the R strain was 10.8 (10.3-11.4) compared
      with the S strain. Resistance was inherited as partly recessive (dominance [D] = 
      0.31) with an estimated RR of 2.3 (2.1-2.4) in the F1 hybrids when the R parent
      was male. There were also significantly male-biased sex ratios for this cross. In
      contrast, inheritance was slightly dominant (D = 0.19) with an estimated RR of
      4.1 (3.8-4.4) when the R parent was female, and no significant sex ratio bias of
      progeny was observed. Analysis revealed a strong paternal-strain effect in
      bioassay mortality, sex ratio, egg hatch, and fecundity. A maternal-strain effect
      was also evident for bioassay mortality. Similarly, a strong maternal by paternal
      strain interaction was also evident for sex ratio. Progeny of single-family
      backcrosses of F1 hybrids to R were statistically homogeneous for sex ratio,
      duration of oviposition, fecundity, and hatch rate. A significant increase in
      male bias was found for only one backcross to R, after treatment with permethrin.
      In contrast, complex patterns of inheritance of life histories were observed
      among backcrosses to S. Backcrosses to S had greater mean fecundities, shorter
      mean times to the start of oviposition, and shorter mean oviposition periods than
      did backcrosses to R. Hatch rates were statistically homogeneous among
      backcrosses, but all strikingly reduced relative to the parental generation.
      Times of start and duration of oviposition were highly negatively correlated with
      fecundity (first gonotropic cycle only) and rate of egg hatch. Females with lower
      fecundities had lower hatch rates, and there was a threshold of approximately 80
      eggs per female, below which no eggs hatched. Generally all backcrosses had
      higher LC50s than expected from single-locus inheritance. Association between sex
      bias and inheritance of resistance was apparent, but no single genetic linkage
      model based on current understanding of sex chromosome genetics was consistent
      with these observations. These results may have epidemiologic importance
      considering that permethrin-soaked bed nets are being used in many countries to
      control the biting activity of disease vectors.

PMID- 9158059
TI  - Recognition of synthetic oligopeptides from nonstructural proteins NS1 and NS3 of
      dengue-4 virus by sera from dengue virus-infected children.
AB  - The nonstructural proteins NS1 and NS3 from dengue virus are involved in the
      immune response during natural infection in humans. To analyze the immunogeneity
      of some epitopes present in NS1 and NS3 proteins from dengue virus type-4, six
      oligopeptides were synthesized; five from NS1 (NS1.1, NS1.2, NS1.3, NS1.4, and
      NS1.5) and one from NS3 (NS3.1). Peptides NS1.1, NS1.2, NS1.3, NS1.5, and NS3.1
      were recognized by sera from dengue virus-infected children, suggesting that they
      represent exposed epitopes during natural dengue virus infection.

PMID- 9158060
TI  - Protection of mice from fatal bubonic and pneumonic plague by passive
      immunization with monoclonal antibodies against the F1 protein of Yersinia
      pestis.
AB  - Monoclonal antibodies (MAbs) to the fraction 1 (F1) protein of Yersinia pestis
      protected mice against fatal pneumonic as well as bubonic plague from wild-type
      F1+ organisms. The rare isolation of a virulent F1- isolate from surviving
      animals supports earlier studies suggesting that improved vaccines should consist
      of immunogens to protect against F1- variants. The high degree of protection with
      IgG MAb suggests that secretory IgA is not required for protection from pneumonic
      plague.

PMID- 9158061
TI  - Evaluation of recombinant chitinase and SXP1 antigens as antimicrofilarial
      vaccines.
AB  - Prior studies indicate that a microfilarial stage-specific chitinase is a
      possible candidate antigen for a transmission-blocking vaccine against Brugian
      filariasis. The antigen is a functional enzyme that progressively appears as
      microfilariae mature and become able to infect and develop in a susceptible
      mosquito vector. It is recognized by a monoclonal antibody that reduces
      microfilaremia in infected animals and by a subset of sera from infected persons
      who remain amicrofilaremic. Immunization of jirds with recombinant chitinase
      induced partial protection against microfilaremia resulting from subsequent
      infection with Brugia malayi, but did not reduce adult worm burdens. Vaccination
      was much less effective when administered during the prepatent stage of infection
      and was ineffective when given to microfilaremic jirds. The protective epitope
      appears to be located close to the carboxy terminus of the chitinase molecule.
      Immunization of jirds with SXP1, an antigen present in multiple worm stages, also
      reduced microfilaremia and, in some experiments, adult worm burdens, but
      hyperimmunization with a recombinant filarial myosin was not protective. These
      observations indicate that the relative timing of immunization and infection is
      an important factor in the efficacy of antimicrofilarial vaccines.

PMID- 9158062
TI  - On the role of gonadotropin-releasing hormone (GnRH) in the operation of the GnRH
      pulse generator in the rhesus monkey.
AB  - The pulsatile secretion of luteinizing hormone (LH), occasioned by the pulsatile
      release of gonadotropin-releasing hormone (GnRH), is closely associated with
      concurrent increases in multiunit electrical activity in the mediobasal
      hypothalamus (MUA volleys), the electrophysiological correlates of GnRH pulse
      generator activity. These volleys represent a highly synchronized increase in
      firing frequency of individual neurons. The origin of these rhythmic oscillations
      in unit activity and the mechanisms responsible for their synchronization are
      unknown. The purpose of the present study was to examine the role, if any, of
      GnRH in the functioning of the GnRH pulse generator in rhesus monkeys.
      Ovariectomized animals bearing recording electrodes chronically implanted in the
      mediobasal hypothalamus and fitted with intracerebroventricular (ICV) cannulae in
      the lateral ventricle and with indwelling cardiac catheters were studied. LH was
      measured in venous blood withdrawn from the cardiac catheters every 10 min while
      hypothalamic electrical activity was monitored continuously. In Experiment 1,
      following a 3- to 4-hour control period, GnRH was infused ICV at a rate of 300
      ng/kg body weight (BW)/h over 4-5 h. In Experiment 2, antide, a long-acting GnRH
      antagonist, was injected ICV in a dose of 105 microg/kg BW after a control period
      of 3-4 h. Additional control experiments were performed in each animal using
      vehicle alone. Neither GnRH nor antide affected the frequency of MUA volleys and
      attendant LH pulses despite significant alterations in LH secretion. These
      results suggest that, in the rhesus monkey, GnRH may not be involved in the
      operation of the GnRH pulse generator.

PMID- 9158063
TI  - Expression of estrogen and progesterone receptors in glutamate and GABA neurons
      of the pubertal female monkey hypothalamus.
AB  - We have previously reported direct glutamate (Glu) synapses upon GnRH-containing
      neurons in the primate hypothalamus, and extensive interactions between Glu and
      aminobutyric acid (GABA) neurons in areas associated with reproductive function.
      Both Glu and GABA are known to affect peripubertal GnRH neurohormone release, but
      their relative roles remain unclear. In a developmental survey, estrogen
      receptors (ER) and progesterone receptors (PR) were virtually undetectable after
      immunostaining the hypothalamus of prepubertal monkeys, but were clearly evident
      in neurons of adults. We hypothesized, therefore, that Glu and GABA neurons which
      develop ER or PR expression during puberty may participate in reactivation of the
      hypothalamic-pituitary-gonadal axis. To identify those neurons in midpubertal
      female cynomolgus monkeys, we performed immunofluorescence staining for ER or for
      PR in separate sets of hypothalamic sections, and then immunostained for Glu or
      for glutamate decarboxylase (GAD, to identify GABA neurons) using a contrasting
      fluorophore. ER and PR were localized in the cytoplasm and nuclei of Glu and GAD
      neurons in nine hypothalamic and related brain regions. Quantitation revealed
      intranuclear ER in an average of 80% of the Glu neurons in all regions analyzed,
      and an average of 84% of the GAD neurons in all regions except the supraoptic
      nucleus (28%). Intranuclear PR expression was more variable, occurring in an
      average of 93% of the Glu neurons in seven regions, but in only 41% in the medial
      preoptic area, and 0% in the arcuate-periventicular zone. In addition, while
      intranuclear PR was seen in 96% of the GAD neurons in the septum, it appeared in
      67% of the GAD neurons in the paraventricular nucleus, 47% in the medial preoptic
      area, 40% in the periventricular zone, and was absent from neurons in the
      supraoptic nucleus and mammillary bodies. In summary, certain subpopulations of
      Glu and GABA neurons in principal hypothalamic regions of the female monkey
      express ER and PR at midpuberty. Taken together with previous findings, these
      results suggest that Glu and GABA neurons which become sensitive to steroid
      hormones may help regulate GnRH neurohormone release and promote the onset of
      puberty. Since neuronal expression of ER or PR connotes sensitivity to gonadal
      feedback, and intranuclear translocation signals transcriptional activation,
      these results provide insights into the specific neuronal events involved in the
      peripubertal transition in primates.

PMID- 9158064
TI  - Estrogen and progesterone receptor expression in neuroendocrine and related
      neurons of the pubertal female monkey hypothalamus.
AB  - Expression of hypothalamic estrogen receptors (ER) and progesterone receptors
      (PR) is barely evident in prepubertal monkeys but is prominent in adults. To
      investigate whether adult patterns of ER and PR expression are established in mid
      pubertal female cynomolgus monkeys, we labeled neuroendocrine (NEU) neurons by
      microinjection of retrograde tracer into the median eminence, and then identified
      ER and PR by specific immunostaining in separate sets of hypothalamic sections.
      ER and PR appeared in the cytoplasm and nuclei of cells identified exclusively as
      neurons, and retrograde tracer remained clearly visible in the cytoplasm of NEU
      neurons after immunostaining. Numbers of NEU and related neurons expressing ER or
      PR were quantified in principal hypothalamic regions. In the supraoptic nucleus,
      almost all neurons analyzed (n = 580) contained ER (94%) with many also NEU (73%
      ER + NEU), while lesser amounts of the neurons examined (n = 214) expressed PR
      (75%) and were NEU (53% PR + NEU). In the paraventricular nucleus, most of the
      neurons analyzed (n = 302) contained ER (90% ER; 54% ER + NEU), but few of the
      neurons studied (n = 269) contained PR (34% PR; 19% PR + NEU). In the
      periventricular zone, nearly all neurons examined (n = 795) contained ER (95% ER;
      48% ER + NEU), but fewer of those studied (n = 298) exhibited PR (79% PR; 47% PR
      + NEU). In the arcuate-periventricular zone, all neurons examined (n = 542)
      contained ER (100%) but few were NEU (4% ER + NEU), while nearly all neurons
      studied (n = 418) contained PR (95%), some of which were NEU (21% PR + NEU).
      Neurons expressing ER were also prevalent in areas without NEU labeling,
      including the diagonal band of Broca, medial preoptic area, and mammillary
      bodies, but were less common in the septum and dorsomedial hypothalamus.
      Likewise, neuronal PR expression was seen frequently in the mammillary bodies,
      but occurred less often in the diagonal band of Broca, medial preoptic area, and
      dorsomedial hypothalamus. Neurons in the suprachiasmatic nucleus and lateral
      hypothalamic area lacked retrograde labeling. These results identify the
      principal sites and subsets of NEU and related neurons which express ER and PR in
      the mid-pubertal female monkey hypothalamus. They appear to correlate well with
      known populations of steroid-sensitive NEU neurons present in these areas in
      adults. The data also suggest that functional patterns of ER and PR expression
      arise upon reactivation of the hypothalamic-pituitary-gonadal axis at puberty.
      The degrees of receptor expression and of nuclear translocation most likely
      reflect peripubertal changes in the levels of gonadal steroids. Taken together,
      these results provide important insights into the mechanisms and development of
      neuroendocrine control during the pubertal period in primates.

PMID- 9158065
TI  - RU 486 blocks and fluoxetine augments progesterone-induced prolactin secretion in
      monkeys.
AB  - Progesterone (P) stimulates prolactin secretion through an unknown neural
      mechanism in estrogen (E)-primed female monkeys. Serotonin also stimulates
      prolactin secretion and this laboratory demonstrated that E induces nuclear
      progestin receptors (PR) in serotonin neurons. Thus, PR in serotonin neurons
      could transduce the action of P on prolactin secretion. Studies were performed to
      determine (1) whether blocking nuclear PR would block P-induced prolactin
      secretion and conversely; (2) whether increasing serotonin concentrations in the
      synapse would augment P-induced prolactin secretion. In both studies, female
      monkeys were spayed, adapted to a vest and tether remote sampling system and
      catheterized prior to experiments. Monkeys received 2 E-filled silastic implants
      (3.0 cm) 1-3 weeks prior to study. P (20 mg) in corn oil was injected (s.c.) to
      transiently increase prolactin secretion. In both studies, each monkey served as
      its own control. To block nuclear PR and not membrane PR, RU 486 (2 mg/kg, i.m.)
      or ethanol (control) was administered with the P injection. Relative to the P
      injection, blood samples were taken twice daily from -30 to +24 h, then every 4 h
      from +36 to +48 h and once at +65 h. To increase serotonin in the synapse, the
      serotonin reuptake inhibitor, fluoxetine (5 mg/day, i.v.), was infused for 4
      weeks. P was injected during the week of vehicle infusion and during the last
      week of fluoxetine infusion. Blood samples were obtained twice daily prior to and
      following P treatment. Prolactin, E, P and RU 486 concentrations were determined
      by RIA. RU 486 completely blocked the P-induced prolactin surge (n = 3). In
      addition, fluoxetine significantly increased prolactin secretion during the P
      induced prolactin peak compared to equal time points during saline infusion (n =
      5). These data indicate that P induces prolactin via a genomic mechanism and not
      through a membrane action. The data also support a pivotal role for serotonin in
      the neural regulation of P-induced prolactin secretion.

PMID- 9158066
TI  - Hypoglycemia-induced inhibition of LH and stimulation of ACTH secretion in the
      rhesus monkey is blocked by alprazolam.
AB  - Insulin-induced hypoglycemia inhibits luteinizing hormone (LH) secretion and has
      been used as a model to study stress-induced inhibition of reproductive function.
      Endogenous opioid peptides have been implicated in mediating the inhibitory
      effect of hypoglycemia on LH secretion in sheep and rat. The objective of the
      present study was to determine if corticotropin-releasing hormone (CRH) and
      endogenous opiates are involved in the LH response to hypoglycemia in the
      nonhuman primate. Blood samples were collected at 15-min intervals for 6 h from
      ovariectomized rhesus monkeys (n = 6). Hypoglycemia was induced by injecting
      insulin 1 h after initiating blood collection. Animals were pretreated 15 min
      prior to insulin with either saline (n = 6), naloxone, a nonselective opiate
      receptor antagonist (n = 4), or alprazolam (n = 6), a potent benzodiazepine which
      has been shown to inhibit CRH. The LH, glucose, adrenocorticotropin (ACTH), and
      cortisol responses to insulin were determined. Insulin-induced hypoglycemia
      significantly inhibited LH secretion and increased ACTH and cortisol
      concentrations. Alprazolam prevented hypoglycemia-induced inhibition of LH
      independent of an effect on glucose concentrations. The mean (+/- SEM) LH pulse
      interval in response to hypoglycemia was decreased in the alprazolam pretreated
      group compared to the saline pretreated group (77.4 +/- 6.0 vs. 130.0 +/- 18.4
      min), while LH pulse amplitude and mean LH levels were significantly increased
      (56.2 +/- 7.1 vs. 28.3 +/- 5.5 ng/ml, and 105.6 +/- 14.4 vs. 60.9 +/- 12.1 ng/ml
      respectively). In contrast, naloxone did not prevent hypoglycemia-induced LH
      inhibition. The mean LH pulse interval, LH pulse amplitude, and LH concentration
      in the naloxone pretreated monkeys were 152.1 +/- 33.4 min, 37.1 +/- 8.9 ng/ml,
      and 63.7 +/- 9.1 ng/ml respectively. Alprazolam pretreatment also markedly
      attenuated the ACTH response to hypoglycemia whereas the cortisol response was
      only moderately affected. We conclude that insulin-induced hypoglycemia in the
      monkey inhibits LH secretion through a mechanism involving CRH but not endogenous
      opiates.

PMID- 9158067
TI  - Impaired adaptation of the hypothalamic-pituitary-adrenal axis to chronic ethanol
      stress in aged rats.
AB  - Acute injection of ethanol in young rats stimulates corticosterone secretion, and
      repeated daily ethanol injection results in tolerance to this response. This
      study examined the tolerance development of the corticosterone response to 14
      daily ethanol injections (2 g/kg i.p.) in young (3-month-old) and aged (24-month
      old) male rats. By day 7 the young rats exhibited complete tolerance to the
      stimulatory effects of ethanol on corticosterone levels, as measured 1 h after
      injection. In contrast, the aged rats displayed a fairly large corticosterone
      response to ethanol on day 7, and they still exhibited a significant
      corticosterone response to ethanol on day 14. There was no difference between
      young and aged rats in blood ethanol levels at any time point examined, and blood
      ethanol levels did not change across days of treatment, indicating that neither
      the tolerance development, nor the age-related difference in tolerance
      development could be explained by time- and age-related differences in ethanol
      metabolism. There also was little evidence for the impaired tolerance development
      in the aged rats to be secondary to a generalized dysregulation of the
      hypothalamic-pituitary-adrenal (HPA) axis following 2 weeks of ethanol treatment.
      Thus, there was no difference in basal corticosterone levels between young and
      aged rats on each test day, and there was no difference between young and aged
      rats in the corticosterone response to an acute restraint stress challenge when
      administered 24 h after the last day of ethanol treatment. This study suggests
      that in aged rats there are changes in the adaptive mechanisms contributing to
      tolerance of the HPA axis response to ethanol.

PMID- 9158068
TI  - Adaptation to prolonged or repeated stress--comparison between rat strains
      showing intrinsic differences in reactivity to acute stress.
AB  - Sprague-Dawley (SD), Fischer 344 (F344) and Lewis (LEW) rats are used in a wide
      variety of laboratory studies. Compared to SD and LEW rats, F344 rats show
      significantly greater activation of the hypothalamic-pituitary-adrenal (HPA) axis
      in response to acute stress, or to immunologic challenge. These differences in
      HPA axis responsivity have been the basis for numerous studies investigating
      strain differences in immunological and behavioral parameters. However, strain
      differences in the adaptation of the HPA axis response to prolonged stress, or to
      repeated stress, have not been investigated. This series of studies demonstrates
      that F344 rats maintain significantly higher ACTH and corticosterone levels than
      SD and LEW rats during a single prolonged stress session. Furthermore, F344 rats
      show virtually no habituation or adaptation of the corticosterone stress response
      during a single prolonged (4 h) stress session, or during stress sessions
      repeated over a period of 10 days. In contrast, SD and LEW rats show habituation
      both within and across stress sessions. Strain differences in HPA axis
      responsivity are also reflected in the significant adrenal hypertrophy observed
      in F344 rats (but not in SD or LEW rats) following repeated stress. These results
      show that strain differences in HPA axis responsivity, which are observed under
      conditions of acute stress, are further amplified during prolonged or repeated
      stress. These differences under prolonged or repeated stress conditions may
      consequently magnify the behavioral and immunological differences observed
      between strains under basal as well as challenged conditions.

PMID- 9158069
TI  - Effect of somatostatin-28 on growth hormone response to growth hormone-releasing
      hormone--impact of aging and lifelong dietary restriction.
AB  - The present study was designed to investigate the modulating effect of aging and
      lifelong dietary restriction (DR), a powerful anti-aging intervention in
      laboratory rodents, on growth hormone (GH) secretion from pituitary cells in
      response to GH-releasing hormone (GHRH) in the presence of somatostatin (SS)-28.
      Dispersed pituitary cells from 6- and 24-month-old rats fed ad libitum (AL-Y, AL
      O, respectively) and 24-month-old rats dietary restricted from 6 weeks of age (DR
      O) were subjected to a reverse hemolytic plaque assay under variable conditions
      including GHRH (0, 1, 10 nM) and SS-28 (0, 10 nM). The proportion of GH plaque
      forming cells in dispersed pituitary cells increased by GHRH and decreased by SS
      28. The proportion of these cells was lowest in AL-O rats; it was lower in DR-O
      than in AL-Y rats, particularly in the presence of SS-28. The reduction in these
      cells by SS-28 was greatest in Group AL-O. The mean area of these plaques,
      reflecting the amount of GH released from individual cells, was not different
      among the three rat groups in the absence of SS-28. In contrast, SS-28 produced a
      significantly higher reduction in the plaque area in Group AL-O compared with AL
      Y and DR-O rats. Our results indicated that: (1) aging did not alter the
      responsiveness of GH-secreting cells to GHRH for GH secretion, while increased
      sensitivity of GH-secreting cells to SS-28 was noted in aged rats; (2) lifelong
      dietary restriction did not modulate the responsiveness to GHRH but partially
      inhibited the age-related increase in the sensitivity to SS-28 of GH-secreting
      cells, and (3) the major impact of the dietary regimen may include modulation of
      the number of pituitary cells, which leads to a high proportion of GH-secreting
      cells compared with that in AL rats at the same chronological age.

PMID- 9158071
TI  - Cardiovascular disease prevention in postmenopausal women: a clinician's
      perspective.

PMID- 9158070
TI  - Electroconvulsive seizures increase levels of PS4, the TRH-enhancing peptide
      [prepro-TRH(160-169)], in rat brain.
AB  - We report the development of a radioimmunoassay for prepro-TRH(160-169) (PS4), a
      thyrotropin-releasing hormone (TRH) enhancing peptide, and its use in
      characterizing the effect of electroconvulsive seizures on the levels of this
      peptide in various brain regions of male Wistar rats. We found that
      electroconvulsive seizures significantly elevated the PS4 levels in hippocampus,
      amygdala, pyriform (olfactory) cortex, and anterior cortex but not in striatum,
      motor cortex, locus ceruleus, or ventral lateral medulla. The levels of PS4 were
      highly correlated with the corresponding TRH (p-Glu-His-Pro-NH2) and TRH-Gly (p
      Glu-His-Pro-Gly) levels in hippocampus, amygdala, and pyriform cortex, consistent
      with the prepro-TRH source of all of these peptides. The PS4 levels in
      hippocampus and amygdala were significantly correlated with the immobility time
      in the Porsolt forced swim test, an established animal model for antidepressant
      effects. The PS4 levels in peripheral blood, hypothalamus, anterior cortex,
      amygdala, and eyes increased severalfold at 20 min following intracisternal
      injection of 228 microg of this peptide, suggesting that it readily crosses the
      blood-brain barrier. The pituitary levels of PS4 and TRH-Gly, on the other hand,
      were decreased within 20 min by intracisternal PS4, suggesting PS4 stimulated the
      release of prepro-TRH peptides from the pituitary. Fresh rat and human serum
      rapidly degraded PS4, indicating that it may act primarily as a paracrine
      modulator of TRH effects in pituitary, brain, and reproductive system.

PMID- 9158072
TI  - Alternative drug use for the climacteric in Finland.
AB  - OBJECTIVES: To investigate the use of alternative drugs for the climacteric in
      Finland, which products are used, and who are the women using them. METHODS: The
      study was based on a population-based survey conducted in 1989 among 2000 Finnish
      women aged 45-64 (response rate 86%). RESULTS: 11% of the women reported the use
      of alternative drugs for the climacteric. Food supplements and bee products were
      the most common types of alternative drugs used. Some of them may have allergic
      or other side effects. Users differ little from other women judging by health
      habits and the utilization of health care services. The best predictors for
      alternative drug use were urban residence, more than 9 years of general
      education, and among 50 54-year olds, the use of prescription or OTC drugs for
      menopause. Over half of the users of alternative drugs had also used hormone
      therapy. CONCLUSIONS: Women using alternative drugs during and after the
      climacteric represent a large group. More information is needed about the
      clinical effects of alternative drugs, and the characteristics of alternative
      drug users.

PMID- 9158073
TI  - Climacteric symptoms do not impair cognitive performances in postmenopause.
AB  - OBJECTIVE: To investigate whether information processing and attention
      performances are affected by climacteric vasomotor symptoms. METHODS: The study
      group comprised 66 healthy hysterectomized postmenopausal women. The subjects
      were divided into two subgroups (high symptomatic and low symptomatic) according
      to the quantity of climacteric vasomotor symptoms. Information processing was
      examined using CogniSpeed, a reaction time software that separates, for example,
      pure controlled processing and working memory from perceptual and motor
      components. Attention was examined by using visual and auditory tasks. The role
      of climacteric depression as a determinant of cognitive performance was evaluated
      by the Beck Depression Inventory and dividing subjects according to self-reported
      climacteric mood symptoms. The effects of serum oestrogen level and ageing on
      cognitive performances were also studied. RESULTS: Cognitive performances were
      similar in high symptomatic and low symptomatic women. On the Verification test
      younger women had shorter reaction times (P = 0.002) and on the Subtraction test
      they had fewer errors (P = 0.015) than older women. These tests required working
      memory and decision making. Accuracy in the tests of sustained and auditory
      attention worsened slightly with age. Cognitive performances neither correlated
      with scores on the Beck Depression scale nor with serum oestrogen level.
      Climacteric mood symptoms did not impair cognitive performance. CONCLUSIONS:
      Despite subjective complaints of memory impairment in association with
      climacteric vasomotor symptoms, our results did not support a direct cause-and
      effect relationship. Thus, the minor deficits found in cognitive processing
      efficiency seem to be related rather to age than climacteric symptoms.

PMID- 9158074
TI  - Age-related changes in body composition of healthy and osteoporotic women.
AB  - OBJECTIVES: The study was carried out to assess age-related changes of body
      composition and to evaluate the influence of lean and fat mass in bone mineral
      density of healthy and osteoporotic women. METHODS: 166 healthy women in
      premenopause (43.2 +/- 6.7 years), 591 healthy postmenopausal women (59.9 +/- 8.1
      years) and 373 women with established involutive osteoporosis (66.2 +/- 7.8
      years) were evaluated: bone mineral density (BMD) and soft tissue composition
      (fat mass, lean mass) were measured by a total body Lunar DPX device. RESULTS: no
      difference in lean mass was appreciated between the groups. Fat mass was
      significantly lower in premenopausal women (19.5 +/- 6.5 kg) and osteoporotic
      patients (18.8 +/- 5.2 kg) than in postmenopausal healthy women (21.8 +/- 5.7
      kg). In premenopause weight, soft tissue mass and fat mass increased with age (P
      < 0.05). In postmenopause, lean mass decreased significantly in healthy women (P
      < 0.05). Fat mass was lower in the osteoporotics than in normals. Total BMD
      correlated significantly with fat and lean mass in all groups (P < 0.01).
      BMD/height ratio correlated significantly with fat mass (P < 0.01), not with lean
      mass. CONCLUSIONS: BMD is closely related to fat mass in healthy premenopausal
      and postmenopausal women, and in osteoporotic patients; osteoporotic patients and
      healthy premenopausal women are characterized by a lower fat mass than healthy
      postmenopausal women; fat mass may be considered one of the determinants of bone
      mass also in involutive osteoporosis.

PMID- 9158075
TI  - Endometrial sonographic and histologic findings in women with and without
      hormonal replacement therapy suffering from postmenopausal bleeding.
AB  - OBJECTIVES: To evaluate, in women with postmenopausal bleeding, the effect of
      hormonal replacement (HRT) therapy on the endometrial thickness as measured by
      transvaginal sonography in relation to endometrial histology. METHODS: 1110 women
      with sequential/progestin treatment (E + P) (n = 202), with Estriol treatment (n
      = 149) or without HRT (n = 759) and postmenopausal bleeding were examined by
      transvaginal sonography (TVS) prior to curettage, with special reference to the
      relation of endometrial thickness to its histopathology. RESULTS: The
      distribution of endometrial pathology was different in those women with E + P and
      Estriol compared with those without HRT. Endometrial pathology was found most
      frequently in women with an endometrium exceeding 8 mm in thickness. Furthermore,
      the incidence was found to increase with increasing endometrial thickness in all
      treatment groups. Atrophy was found significantly more often in women without
      HRT. Hormonal effects on the endometrium were found significantly more often in
      women with E + P and Estriol. Endometrial hyperplasia was found most commonly in
      women with Estriol in the thickness group 5 8 mm (P < 0.001) as compared to those
      with HRT and without HRT. Endometrial cancer occurs most in women without HRT, in
      those women with an endometrium exceeding 8 mm in thickness as compared both to
      the E + P (P < 0.001) group and to the Estriol (P < 0.001) group. Endometrial
      cancer did not occur in any woman (with E + P, Estriol or without HRT) with an
      endometrial thickness of < or = 4 mm. CONCLUSIONS: TVS is of value for excluding
      endometrial pathology in women with HRT and postmenopausal bleeding. The
      distribution of endometrial findings and histopathological diagnosis in women
      with abnormal postmenopausal bleeding was different in women with E + P than in
      women without HRT. Furthermore, the cut-off for excluding endometrial
      abnormalities is the same in both groups i.e. < or = 4 mm.

PMID- 9158076
TI  - Estrogen response in buccal mucosa -- a cytological and immunohistological assay.
AB  - OBJECTIVES: The aims of the present study were firstly, to evaluate the effect of
      estrogen on the cytology of buccal mucosa during the menstrual cycle and at
      menopause, and, secondly, to analyze the presence of estrogen receptors in the
      epithelial cells of buccal mucosa using immunohistochemical methods. METHODS: The
      cytological samples of buccal mucosa from 10 healthy young women (mean age 24
      years) were taken on every day of the menstrual cycle and stained according to
      Papanicolaou. A single cytological sample of buccal mucosa was also collected
      from 20 healthy postmenopausal women (mean age 66 years) using no hormone
      replacement therapy. For each specimen, a maturation index was calculated on the
      basis of percentages of the three (parabasal, intermediate and superficial) cell
      types. Moreover, 50 incisional biopsies were taken from buccal mucosa of 50 young
      healthy women (19 years old) for analysis of estrogen receptor expression by
      immunohistochemistry using an indirect immunoperoxidase technique. RESULTS: On
      cytohormonal evaluation, intermediate cells were dominant in postmenopausal women
      and also in young women at all stages of the menstrual cycle indicating a nearly
      complete cell maturation. Estrogen receptor positive cells were not detected in
      buccal epithelium by immunohistochemistry. CONCLUSIONS: As the cell pattern of
      buccal mucosa indicated a nearly complete cell maturation both in young and in
      postmenopausal women, estrogen may not be the only factor causing maturational
      changes in buccal epithelial cells. Alternatively, the antibody used in
      immunohistochemistry may not detect the epitope of the estrogen receptor present
      in buccal mucosa or the level of expression of this protein may be under the
      detection limit.

PMID- 9158077
TI  - Carotid artery wall thickness in women treated with hormone replacement therapy.
AB  - OBJECTIVE: To measure the thickness of the individual layers (externa, media,
      intima) of the carotid artery in two groups of postmenopausal women. METHODS: A
      high resolution ultrasound (25-MHz Osteoson DIII Minhorst) was used to assess the
      distal end of the common carotid artery. Forty-six women were on hormone
      replacement therapy (Premarin 0.625 mg and Norgestrel 1 mg) for more than 1 year.
      The measurements of the treated group were compared to those of 51 postmenopausal
      women who acted as controls. RESULTS: No significant difference between the
      externa and media layers of both groups of women were noted. The media showed a
      tendency to be thicker in the treated group. The intima of the untreated group
      was found to be significantly thicker than that of the treated group (P < 0.05).
      Significant correlations were found between the layers of the carotid artery
      especially between the externa and media both mainly composed of connective
      tissue (Collagen Type I and III and elastin). The media/intima ratio of the
      treated women was significantly higher than that of the untreated group (P<
      0.003). CONCLUSION: It is postulated that the changes observed may be due to the
      effect of oestrogen on connective tissue. These arterial changes induced by
      hormone replacement therapy may partially explain the cardioprotective effect
      this treatment has on postmenopausal women. The increased intimal thickness in
      untreated women compared to treated ones on the other hand would represent the
      reduction in atheromatous plaque formation in women on oestrogen replacement
      therapy.

PMID- 9158078
TI  - The effect of body composition on bone density in pre- and postmenopausal women.
AB  - OBJECTIVES: To investigate the relative contribution of body composition (lean
      and fat) to bone mineral density (BMD), 196 premenopausal and 128 postmenopausal
      Japanese women were enrolled. METHODS: Total fat mass, total lean mass, lumbar
      BMD (L2-L4), and total body BMD were measured by dual-energy X-ray absorptiometry
      (DEXA, Hologic QDR 2000, MA. USA). Physical characteristics were also recorded
      for each subject. Correlation between BMD and variables were calculated for each
      of the two groups in single and stepwise regression analyses. RESULTS: Total lean
      mass was significantly higher in premenopausal women than postmenopausal women (P
      < 0.0001), while body weight, body mass index, and total fat mass were not
      different between the two groups. In stepwise regression analysis, total lean
      mass was the most powerful determinant of lumbar BMD and total body BMD in
      premenopausal women. In postmenopausal women, total fat mass was the most
      significant determinant of lumbar BMD, while total lean mass was the most
      significant determinant of total body BMD. CONCLUSIONS: These findings suggest
      that there is a difference between pre- and postmenopausal women in the relative
      contribution of lean and fat mass. Total lean mass is the most significant
      determinant of BMD in premenopausal women. On the other hand, total fat mass may
      have some advantages in maintaining BMD in postmenopausal women.

PMID- 9158079
TI  - Bone effects of transdermal hormone replacement therapy in postmenopausal women
      as evaluated by means of ultrasound: an open one-year prospective study.
AB  - OBJECTIVES: To evaluate the effectiveness of transdermal oestrogen replacement
      therapy plus medrogestone (HRT) in postmenopausal bone loss prevention by means
      of US. METHODS: We enrolled 112 healthy postmenopausal women in an open,
      prospective study. These women, after a gynaecological evaluation and an US
      assessment of the skeletal status, were advised to take cyclic sequential
      oestrogen/progestagen therapy: 50 microg/day of transdermal 17beta-oestradiol
      (Rotta Research Laboratorium) plus 5 mg/day of medrogestone, for 12 days per
      cycle (Wyeth-Ayerst). After 1 year we recalled these women: only 32 of them were
      taking HRT, while 49 had declined HRT without taking alternative therapies. The
      remaining women were excluded from the study as they were either unavailable for
      the check-up or they were taking prohibited therapies. We used DBM Sonic 1200
      (Igea, Italy) to assess US parameter changes at phalanxes at enrollment and after
      1 year. This device enabled us to evaluate US transmission velocity (AD-SoS) and
      US attenuation pattern (UBPS). In a previous study we had evaluated the intra-
      and inter-observer reproducibility of AD-SoS measurements (0.4 and 1.0%
      respectively). Using the same data we evaluated the intra- and inter-observer
      precision of UBPS. RESULTS: The UBPS intra-operator reproducibilities were 5.3%
      and 6.1% (for the 1st and the 2nd operator, respectively), while inter-observer
      precision was 8.8%. Both AD-SoS and UBPS significantly decreased in the non-user
      group(-0.7%, P < 0.001 and -14.3%, P < 0.001 respectively). In the user group AD
      SoS showed a significant increase (+0.7%, P < 0.01), while a slight but
      significant decrease was observed for UBPS (-2.8%, P < 0.05). CONCLUSIONS: Our
      findings show that the effectiveness of transdermal HRT in slowing or even
      arresting postmenopausal bone loss can be monitored by quantitative US studies.
      The trend difference observed between AD-SoS and UBPS with and without therapy is
      at least partially explained by a different response to HRT with regard to bone
      density as well as structure.

PMID- 9158080
TI  - Prevention of postmenopausal bone loss with minimal uterine bleeding using low
      dose continuous estrogen/progestin therapy: a 2-year prospective study.
AB  - OBJECTIVE: To re-examine the minimal effective dose of conjugated estrogen (CEE)
      progestin hormone replacement on postmenopausal bone loss. DESIGN: A 2-year,
      prospective, open label, randomized study. SETTING: Department of Obstetrics and
      Gynecology of a university hospital. PARTICIPANTS: Fifty-two postmenopausal or
      oophorectomized women. INTERVENTION: One of the following regimens was
      continuously administered for 2 years: (1) CEE 0.625 mg/day, (2) CEE 0.625 mg +
      medroxyprogesterone (MPA) 2.5 mg/day, (3) CEE 0.31 mg + MPA 2.5 mg/day and (4)
      control. MEASUREMENTS: Lumbar spine and femoral BMD by dual energy X-ray
      absorptiometry (DXA), a monthly based incidence of bleeding, serum lipids, PTH,
      calcitonin. A1-p, and osteocalcin. RESULTS: Of the 52 patients enrolled in this
      study, 49 patients completed the 1 year of therapy and 36 completed the 2- year
      study. The control group showed a significant decrease in lumbar BMD over the 2
      years (P < 0.05). The % changes in lumbar BMD at 2 years of CEE alone, CEE 0.625
      + MPA and CEE 0.31 + MPA were 8.52% (95% confidence intervals; 4.61 approximately
      12.4%), 7.4% (0.60 approximately 14.2%) and 3.20% (0.61 approximately 5.84%),
      respectively, and were significantly higher than pretreatment values. The
      incidence of bleeding was significantly lower in women taking CEE 0.31 mg + MPA.
      HDL cholesterol increased in women taking CEE 0.625 mg alone or with MPA. No
      significant changes in lipid profiles were seen in the control or in the group of
      women taking CEE 0.31 mg + MPA. CONCLUSIONS: Continuous hormone replacement
      therapy (HRT) using 0.31 mg of CEE and 2.5 mg of MPA is effective in increasing
      lumbar BMD in postmenopausal or oophorectomized women and can be an appropriate
      option for women with a normal lipid profile or those women wishing to eliminate
      unscheduled bleeding.

PMID- 9158081
TI  - A comparative study of an estradiol-releasing vaginal ring versus tibolone in
      postmenopausal women: a transvaginal color Doppler study.
AB  - OBJECTIVE: To evaluate endometrial blood flow characteristics in response to
      estrogen replacement therapy (ERT) and tibolone in postmenopausal women and to
      correlate the resistance index (RI) with plasma estradiol levels. MATERIALS AND
      METHODS: Transvaginal color Doppler ultrasound examinations were performed in 72
      asymptomatic, postmenopausal women who demonstrated endometrial thickness < or =
      5 mm. Thirty-six women receiving tibolone and 36 patients receiving ERT by a
      vaginal ring comprised the study groups. RESULTS: All postmenopausal women
      treated with tibolone or ERT showed continuous forward end-diastolic flow. The
      lowest RI was obtained in women with the vaginal ring inserted. The plasma
      concentrations of estradiol were found to be significantly higher in the vaginal
      ring group than those of tibolone. CONCLUSIONS: The data observed suggest that
      ERT and tibolone modify normal postmenopausal endometrial perfusion. Tibolone had
      a weaker estrogenic effect on endometrial blood flow resistance, and vaginal ring
      treatment enhanced endometrial blood perfusion through vasodilatation.

PMID- 9158082
TI  - The effect of tibolone on cardiac flow in postmenopausal women with non-insulin
      dependent diabetes mellitus.
AB  - OBJECTIVE: Postmenopausal women with non-insulin dependent diabetes (NIDDM) are
      frequently obese, hypertensive and hyperlipidaemic and hence at particular risk
      of coronary heart disease (CHD). They might therefore benefit from menopausal
      therapy. In view of the fact that oestrogen replacement increases cardiac flow
      but not limb flow whilst tibolone dilates forearm flow in healthy postmenopausal
      women, a study was undertaken to evaluate the effects of tibolone on cardiac flow
      in postmenopausal women with NIDDM. DESIGN: A prospective 12 months before/after
      intervention study. PATIENTS: 15 postmenopausal women (mean age 58.36 +/- 1.25
      years; mean duration of menopause 115.20 +/- 13.97 months; mean BMI: 26.22 +/-
      1.02) with NIDDM (mean duration of diabetes 106.07 +/- 15.66 months).
      MEASUREMENTS: Cardiac flow was measured every 6 months for 1 year by pulsed
      Doppler echocardiography. The parameters assessed were: stroke volume (SV),
      cardiac output (CO), ejection fraction (EF), pre-ejection time (PEP), ejection
      time (ET), peak systolic flow velocity (PFV), acceleration time (AT), flow
      velocity integral (FVI), mean acceleration (MA), early diastolic filling time
      (Ei), atrial filling time interval (Ai), peak velocity of the early diastolic
      filling (E) and peak velocity of the early atrial filling (A). Blood pressure was
      also recorded during Doppler echocardiography. RESULTS: Stroke volume, cardiac
      output and ejection fraction increased significantly after 6 months. There was
      also a significant increase in peak flow velocity (PFV), flow velocity integral
      (FVI) and mean acceleration (MA) together with a significant increase in early
      diastolic filling time (Ei) and peak velocity of the early diastolic filling (E).
      Blood pressure was unchanged throughout the 12-month study period. CONCLUSION:
      The significant increase in stroke volume, cardiac output and flow velocity over
      the aortic valve parallel the effects of oestrogens in healthy postmenopausal
      women. The fact that tibolone improved left ventricular relaxation suggests the
      drug might help prevent or at least defer the development of cardiac dysfunction
      in diabetic women.

PMID- 9158083
TI  - Acute dopaminergic blockade augments the naloxone-induced LH rise in estrogen
      treated postmenopausal women.
AB  - OBJECTIVES: To assess the effect of estrogen replacement on the simultaneous
      blockade of the dopaminergic (DA) and opioidergic neural control of hypothalamic
      gonadotropic function in postmenopausal women. METHODS: Twenty healthy
      postmenopausal women, 48-55 years old were randomly assigned to receive either a
      4-h naloxone infusion at 2 mg/h (group 1, n = 7) or a 10 mg i.v. bolus of
      metoclopramide (group 2, n = 7) or both drugs, simultaneously (group 3, n = 6)
      before and after 3 weeks of transdermal estradiol (100 microg/day). Blood samples
      were obtained at 30-min intervals during 4 h and duplicate determinations of
      serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol
      (E2) and prolactin (PRL) were performed in all samples. RESULTS: In group 1 only
      a mild but significant LH rise after but not before estrogen replacement was
      seen. In group 2 PRL had a greater rise after than before estrogen therapy,
      without other hormonal changes. In group 3 a greater rise in PRL occurred after
      than before estrogen administration and serum LH had a sustained rise throughout
      the test only after estrogen replacement (greater than in group 1). No FSH
      changes were observed. The after-estradiol PRL response was nearly similar in
      groups 2 and 3. CONCLUSIONS: Our results indicate that in the untreated
      postmenopausal women, the dopaminergic system has little and the opioidergic
      system has no significant input in the control of gonadotropin or prolactin
      release. However, following estrogen replacement, opioids are involved in the
      inhibition of LH release and stimulating PRL release, while the dopaminergic
      system acts to inhibit PRL release and modulates LH release or inhibition,
      depending on the levels of circulating estrogens.

PMID- 9158084
TI  - The systemic lupus erythematosus (SLE) disease autoantigen-calreticulin can
      inhibit C1q association with immune complexes.
AB  - Following its release from cells during infection and inflammation, calreticulin
      (CRT) can act as an autoantigen in diseases such as SLE. Why CRT is a target of
      protective immunity and whether it may interfere with innate immunity once
      released from cells during inflammation is unclear. In the present study, we
      found that CRT was detected more frequently in SLE sera and in higher amounts
      than found in control sera. Approximately 40% of SLE sera tested contained
      autoantibodies against CRT as detected by ELISA and immunoblotting. CRT was found
      to be predominantly in the sera of SLE patients associated with immune complexes
      and C1q, and only bound to the surfaces of neutrophils in the presence of low
      levels of calcium and magnesium. In order to further investigate the C1q-CRT
      interaction, recombinant CRT and its discrete domains (N-, P-, and C-domains)
      were produced in Escherichia coli. CRT binds to globular head region of C1q
      primarily via its N- and P-domains. The N-domain was shown to be the most
      autoantigenic region of CRT, as the anti-CRT autoantibodies from most patients
      reacted against this region. CRT also altered C1q-mediated immune functions. The
      P-domain of CRT bound to C1q and reduced the binding of immune complexes in SLE
      sera to immobilized C1q. Full length CRT and its N- and P-domains were able to
      reduce the C1q-dependent binding of immune complexes to neutrophils and solid
      phase bound C1q. We conclude that CRT, once released from leucocytes during
      inflammation, may not only induce an antigenic reaction, but also interfere with
      C1q-mediated inflammatory processes.

PMID- 9158085
TI  - Fine specificity of autoantibodies to La/SSB: epitope mapping, and
      characterization.
AB  - The B cell epitope mapping of La/SSB was performed using 20mer synthetic peptides
      overlapping by eight amino acids covering the whole sequence of the protein. IgG,
      purified from sera of five patients with systemic lupus erythematosus (SLE) and
      four sera from patients with primary Sjogren's syndrome (pSS) were tested against
      the overlapping synthetic peptides. Peptides highly reactive with purified IgG
      were those spanning the regions 145-164, 289-308, 301-320 and 349-368 of the La
      protein. Determination of the minimum required length of the antigenic
      determinants disclosed the following epitopes: 147HKAFKGSI154,
      291NGNLQLRNKEVT302, 301VTWEVLEGEVEKEALKKI318 and 349GSGKGKVQFQGKKTKF364.
      Predicted features and molecular similarities of the defined epitopes were
      investigated using protein databases. The La epitope 147HKAFKGSI154 presented
      83.3% similarity with the 139HKGFKGVD146 region of human myelin basic protein
      (MBP) and 72% similarity with the fragment YKNFKGTI of human DNA topoisomerase
      II. Peptides corresponding to these sequences cross-reacted with anti-La/SSB
      antibodies. Sixty-three sera with anti-La/SSB antibodies from patients with pSS
      or SLE, 35 sera without anti-La/SSB antibodies from patients with SS or SLE and
      41 sera from age/sex-matched healthy blood donors were tested against
      biotinylated synthetic epitope analogues in order to determine their sensitivity
      and specificity for the detection of anti-La/SSB antibodies. Anti-La/SSB were
      detected with various frequencies ranging from 20% to epitope 147HKAFKGSI154 to
      100% to epitope 349GSGKGKVQGKKTKF364. The overall sensitivity and specificity
      using all assays with the synthetic peptides were found to be 93.6% and 85.6%,
      respectively. In conclusion, antibodies to La/SSB constitute a heterogeneous
      population, directed against different linear B cell epitopes of the molecule.
      The epitope 147HKAFKGSI154 presents molecular similarity with fragments of two
      other autoantigens, i.e. human MBP and DNA topoisomerase II. Finally, synthetic
      epitope analogues exhibit high sensitivity and specificity for the detection of
      anti-La/SSB antibodies.

PMID- 9158086
TI  - Effects of rapamycin on apoptosis of rheumatoid synovial cells.
AB  - In the present study, we investigated the effects of an immunosuppressant,
      rapamycin, on bcl-2 expression and the susceptibility of human rheumatoid
      synovial fibroblasts to Fas-mediated apoptosis. Rapamycin treatment down
      regulated bcl-2 expression on rheumatoid synovial cells in a dose-dependent
      manner. In contrast, Fas antigen expression was not influenced by rapamycin
      treatment. Rapamycin treatment also enhanced the susceptibility of rheumatoid
      synovial cells to anti-Fas monoclonal antibody-mediated apoptosis. Our results
      suggest that rapamycin augments the sensitivity of rheumatoid synovial
      fibroblasts to apoptosis by down-regulating bcl-2 expression. This
      pharmacological alteration of sensitivity to apoptosis in the rheumatoid synovium
      may represent a new therapeutic approach for rheumatoid arthritis.

PMID- 9158087
TI  - Characterization of T cells specific for an epitope of human 60-kD heat shock
      protein (hsp) in patients with Behcet's disease (BD) in Japan.
AB  - BD is prevalent in the area of the Silk Route. It has been shown that hsp are
      involved in the T cell activation in patients with BD in the UK, where this
      disease has developed sporadically. We have thus examined whether the T cell
      response to the hsp-derived peptides may be induced in patients with BD in Japan,
      an east pole of the Silk Route. As with patients in the UK, the human 60-kD hsp
      peptide 336-351 also yielded vigorous proliferation of T cells in Japanese
      patients with BD, but neither in normal subjects nor in patients with rheumatoid
      arthritis (RA); there was significant association between proliferation by this
      peptide and the presence of ocular lesion, but not any other symptoms of BD. To
      clarify whether the peptide stimulates T cells as a polyclonal activator, a
      specific antigen or a superantigen-like substance, we analysed T cell receptor
      (TCR) usage of responding T cells by means of MoAbs specific for TCR Vbeta
      subfamily and polymerase chain reaction (PCR)-single-strand conformation
      polymorphism (SSCP)-based technique. We found that T cells with certain TCR Vbeta
      subfamilies (including Vbeta5.2-3, 8, 13.6, 18, 21.3) were increased in
      circulation and responded to the hsp peptide in an antigen-specific fashion. In
      addition, TCR Vbeta gene-amplified products of freshly isolated T cells of
      patients with BD formed several bands in the PCR-SSCP analysis; some of them
      became prominent after stimulation with the peptide. This suggests that T cells
      in patients with this disease have already been expanded oligoclonally in vivo,
      which may be a result of stimulation by triggering antigens, including the hsp
      peptide. In addition, hsp peptide stimulation induced proinflammatory cytokine
      mRNA expression in peripheral blood mononuclear cells, including IL-8, tumour
      necrosis factor-alpha (TNF-alpha) and TNF-beta in eight out of eight patients
      studied. Taken together, the results suggest that hsp antigen may play a role in
      the pathogenesis of BD, not only in the area of the Silk Route, but also outside
      the Silk Route area.

PMID- 9158088
TI  - Prevention of collagen-induced arthritis (CIA) by treatment with polyethylene
      glycol-conjugated type II collagen; distinct tolerogenic property of the
      conjugated collagen from the native one.
AB  - Administration of a soluble protein into animals prior to challenge immunization
      induces immunological tolerance which is specific for the protein. In addition,
      chemical modification of proteins with polyethylene glycol (PEG) has been
      reported to convert the immunogenic proteins to become tolerogenic. However,
      differences in tolerogenic properties between PEG-modified proteins and the
      native counterparts have never been analysed. The ability of PEG-conjugated type
      II collagen (PEG-CII) to attenuate CIA, an animal model for rheumatoid arthritis,
      was compared with the native unconjugated CII. Groups of DBA/1 J mice were
      treated weekly with i.p. injections with PEG-CII, native CII, or vehicle alone
      for 3 weeks, before they were challenged with CII in adjuvants. The induction of
      tolerance was confirmed in both PEG-CII- and CII-pretreated mice when suppression
      of lymph node T cell proliferation in response to CII was noted. The degrees of
      suppression of T cell proliferation were comparable between the two pretreated
      groups. However, induction of arthritis and production of IgG anti-CII antibody
      were more markedly suppressed in PEG-CII-pretreated mice than in native CII
      pretreated mice, although the severity of arthritis and antibody levels in the
      latter group were also lower than in control mice. IgG2a and IgG2b antibody
      levels were equally suppressed in the two pretreated groups, whereas the IgG1
      level was significantly lower in the PEG-CII-pretreated group than in the native
      CII-pretreated group. The results provide the first evidence that attachment of
      PEG to CII renders the protein more tolerogenic.

PMID- 9158089
TI  - Measurement of deoxyribonuclease I (DNase) in the serum and urine of systemic
      lupus erythematosus (SLE)-prone NZB/NZW mice by a new radial enzyme diffusion
      assay.
AB  - A new radial enzyme diffusion (RED) method for the measurement of DNase activity
      in serum and urine is described. The sensitivity of the assay is in the range of
      15.6-500 ng/ml. The assay is based on the hydrolysis of double-stranded (ds) DNA
      (or nucleosomes) in agarose. The specificity of the reaction for DNase I was
      established by showing that either EDTA in the reaction buffer or G-actin
      abolished DNase activity. Being a functional assay, RED has advantages over
      radioimmunoassay (RIA) or ELISA, since antigenic assays may also measure
      complexes of DNase with actin. This method was used to measure DNase activity in
      the sera and urine of lupus-prone mice (NZB/NZW F1 hybrids, aged 4-6 weeks).
      Serum DNase activity in these mice was significantly lower (mean 9 ng/ml) than in
      control, normal mice of the same age and sex (mean 37 ng/ml). Concentration of
      DNase in the urine of 4-6-week-old female NZB/NZW F1 hybrids (24 ng/ml) was
      significantly lower then in control mice (521 ng/ml). The RED method was used to
      measure the concentration of actin as the DNase inhibitor in serum. G-actin in
      the presence of ATP binds DNase and inhibits its nucleolytic activity. Since ATP
      is necessary for the actin inhibition of DNase I, this shows that there is actin
      as well as DNase I in the serum. Actin is not only ATP-dependent, but also heat
      labile. Heating the sera for 10 min at 50 degrees C increases DNase activity.
      This is an alternative method for measuring the concentration of actin in the
      serum. An almost identical estimate of actin concentration in sera of normal mice
      was found from the difference of DNase activity in the presence or absence of ATP
      (mean actin concentration = 21 ng/ml) or from the difference of DNase activity in
      heated and non-heated serum (mean actin concentration 18 ng/ml). We were not able
      to demonstrate DNase inhibitors in the urine of either control or NZB/W F1 hybrid
      mice.

PMID- 9158090
TI  - Oxidized low-density lipoprotein (Ox-LDL) but not LDL aggravates the
      manifestations of experimental antiphospholipid syndrome (APS).
AB  - Ox-LDL is thought to play a major role in atherogenesis. The mechanisms mediating
      the deleterious influences of Ox-LDL include foam cell formation and cell
      cytotoxicity. The production of anti-Ox-LDL antibodies results in the formation
      of immune complexes which are taken up at enhanced rate by macrophages, leading
      to foam cell formation. APS is characterized by repeated venous and arterial
      thromboembolic phenomena, recurrent fetal loss and thrombocytopenia, associated
      with the presence of antibodies to negatively charged phospholipids (aPL) (i.e.
      cardiolipin, phosphatidylserine). Phospholipids bear structural resemblance to
      LDL, and several studies have indeed proved that aPL display cross-reactivity
      with anti-Ox-LDL antibodies. In this study we assessed the capacity of oxidized
      and native forms of LDL to aggravate the clinical picture of experimentally
      induced APS in naive mice. Mice were actively immunized intradermally with
      anticardiolipin antibodies and developed a clinical picture resembling APS in
      humans. Subsequently, the mice were infused with either Ox-LDL, native LDL or
      PBS, and similar regimens were applied to controls. APS mice infused with Ox-LDL
      were found to exhibit a significantly more severe form of the disease in
      comparison with native LDL- and PBS-infused mice, expressed by lower platelet
      counts (261,000/mm3, 535,000/mm3 and 455,000/mm3, respectively), longer activated
      partial thromboplastin time (aPTT) (99 +/- 12 s, 63 +/- 8 s and 74 +/- 8 s,
      respectively) and higher fetal resorption rates (72.7%, 34.4% and 32.6%,
      respectively). The results of this study show that Ox-LDL, compared with native
      LDL, aggravates the clinical manifestations of experimental APS and suggest that
      cross-reactivity of Ox-LDL with phospholipids may provide a pathogenic
      explanation for this effect.

PMID- 9158091
TI  - Up-regulation of the endothelial cell adhesion molecule intercellular adhesion
      molecule-1 (ICAM-1) by autoantibodies in autoimmune vasculitis.
AB  - Autoimmune vasculitis is characterized by the presence of autoantibodies,
      particularly anti-neutrophil cytoplasmic antibodies (ANCA) and anti-nuclear
      antibodies (ANA), in patient sera. These autoantibodies have an incompletely
      understood role in development of vascular injury. The expression or up
      regulation of cell adhesion molecules is an early phase in the development of an
      inflammatory vascular lesion. Autoantibody-positive sera from patients with
      vasculitis were assessed for their ability to modulate adhesion molecule
      expression by human umbilical vein endothelial cells (HUVEC). Autoantibody
      positive serum samples from 11 out of 21 patients with primary vasculitis
      produced substantial up-regulation of ICAM-1 on HUVEC. Autoantibody-negative
      samples did not produce adhesion molecule up-regulation. Up-regulation of
      adhesion molecules on HUVEC was observed with samples positive for ANA, a
      phenomenon not previously reported. Preincubation of the sera with purified
      antigens recognized by ANCA failed to block this activation. In addition, MoAbs
      to ANCA antigens were ineffective at inducing ICAM-1 up-regulation, suggesting
      that activation is independent of the molecular specificity of the antibody. This
      capacity of ANCA- and ANA-positive sera to up-regulate adhesion molecules on
      endothelial cells may be a factor in the vessel wall inflammation seen in ANCA
      associated vasculitis.

PMID- 9158092
TI  - Expansion of restricted cellular immune responses to HIV-1 envelope by
      vaccination: IL-7 and IL-12 differentially augment cellular proliferative
      responses to HIV-1.
AB  - The failure of immune effector mechanisms to control HIV-1 infection has
      important consequences for the human host. In a randomized cohort of HIV-infected
      patients, there was striking in vitro restriction of the proliferative response
      to HIV-1 envelope protein (Env), gp160; only 34% of patients recognized Env.
      Therapeutic vaccination with recombinant gp160 or gp120 (rgp160, rgp120) reversed
      the restriction in vitro, with Env recognition rising to 81%. Peripheral blood
      mononuclear cells (PBMC) from HIV-infected vaccine recipients, placebo
      recipients, and seronegative volunteers were cultured with exogenous IL-7 or IL
      12 and either tetanus toxoid (TT) or gp160. IL-7 significantly augmented
      proliferative responses to TT and gp160, whereas IL-12 only affected
      proliferation to gp160. IL-7, but not IL-12, increased the number of HIV-infected
      placebo recipients who recognized rgp160. IL-12 had its greatest effect in the
      induction of rgp160-specific responses from seronegative individuals. The data
      suggest that these two cytokines have differential activity in the relief of
      restricted cellular immunity to Env; the predominant effect of IL-7 is in
      individuals who have been primed by exposure to antigen, while the effect of IL
      12 is most evident in seronegative, unprimed individuals. Modification of
      restricted proliferative responses to Env by vaccination or cytokines in vitro
      suggests that strategies incorporating IL-7 or IL-12 as adjuvants may selectively
      boost cellular reactivity to HIV-1.

PMID- 9158093
TI  - High serum level of soluble CD30 in acute primary HIV-1 infection.
AB  - CD30 has been suggested to play a role in HIV infection. In this study the serum
      concentration of soluble CD30 (sCD30) was determined by an ELISA essay on samples
      collected from patients with acute primary HIV-1 infection during the acute phase
      (n = 17) and after seroconversion (n = 13). sCD30 during acute infection was
      consistently elevated (137.58 +/- 120.33 versus 6.4 +/- 5.4 U/ml (mean +/- s.d.)
      in normal controls, P<0.0001) and decreased after seroconversion (49.1 +/- 66.17
      U/ml; P = 0.0018 compared with acute infection). This trend mirrored the
      disappearance of detectable levels of HIV antigen in the blood, resulting in a
      direct correlation between sCD30 and HIVAg values (P = 0.002). These data suggest
      that the high levels of sCD30 observed during the peak concentration of HIVAg in
      acute primary HIV infection might reflect the high rate of viral replication.

PMID- 9158094
TI  - Characterization of HIV-related periodontitis in AIDS patients: HIV-infected
      macrophage exudate in gingival crevicular fluid as a hallmark of distinctive
      etiology.
AB  - In an attempt to clarify the immunobiological events featuring periodontitis
      lesions of AIDS patients in the late stage of the disease, peripheral blood (PB)
      and gingival crevicular fluid (GCF) leucocytes from periodontitis lesions of 23
      late-stage AIDS patients were analysed by three-colour flow cytometry for
      detection and identification of intracytoplasmic p24+ cell fractions. The cells
      were reacted with CD14 and CD68 for mononuclear phagocytes or with CD4 and CD14
      for Th cells, then with anti-p24 MoAb. To detect HIV proviral sequences and
      intracellular p24 RNA sequences, genomic DNA and cellular RNA from leucocytes
      were extracted for semi-nested polymerase chain reaction (PCR) amplification.
      CD68+/p24+ and CD14+/CD68+/p24+ fractions were larger in GCF than in PB
      (P<0.0001; P < 0.003). CD14+/p24+ fraction was lower in GCF than in PB (P <
      0.05). The fluorescence intensities (FI) for intracellular p24 in CD68+ and
      CD14+/CD68+ cells were higher in GCF than in PB (P < 0.003; P < 0.02), whereas
      those of CD14+ macrophages did not differ. The p24 FI of CD68+ macrophages in GCF
      correlated with CD4+ lymphocyte counts in PB (P < 0.005). p24 FI levels of CD14+
      monocytes in GCF and PB significantly correlated (P < 0.02), whereas that of
      CD68+ macrophages did not. PCR and reverse transcriptase (RT)-PCR of cellular DNA
      and RNA yielded positive signals, demonstrating viral integration and production
      in GCF leucocytes. These results show that periodontitis lesions in AIDS patients
      can be characterized by a rapid macrophage turnover, and these HIV-infected
      macrophage exudates in GCF may be considered as a within-mouth source of virus.

PMID- 9158095
TI  - Decreased expression of 20-kD homologous restriction factor (HRF20, CD59) on T
      lymphocytes in Epstein-Barr virus (EBV)-induced infectious mononucleosis.
AB  - HRF20 (CD59) is one of the membrane-associated complement regulatory proteins.
      The characteristic function of CD59 is to prevent membrane attack complex (MAC)
      formation on the cell surface and to protect the cell from complement-mediated
      cell lysis. We examined the expression of CD59 antigen on T cell subpopulations
      in patients with acute infectious mononucleosis (IM) and analysed the
      relationship between the amount of CD59 expression and activation-induced cell
      death of mature T cells with apoptosis. Decreased expression of CD59 on CD8+ T
      cells, especially on CD45RO+ and HLA-DR+ activated T cells, was marked in acute
      IM patients. In contrast, activated CD4+ T cells from IM patients expressed as
      much CD59 antigen as CD4+ T cells from healthy volunteers. After incubation
      induced cell death, viable CD8+ T cells showed normal amounts of CD59 antigen on
      their surface. CD59dim CD8+ T cells were more susceptible to apoptosis than
      CD59bright CD8+ T cells. These findings suggest that decreased expression of CD59
      on CD8+ T cells may discriminate the susceptibility of activated CD8+ T cells to
      activation-induced cell death in IM.

PMID- 9158097
TI  - T helper responsiveness in human Loa loa infection; defective specific
      proliferation and cytokine production by CD4+ T cells from microfilaraemic
      subjects compared with amicrofilaraemics.
AB  - The proliferation and cytokine profiles of peripheral blood mononuclear cells
      (PBMC) from microfilaraemic (Mf+) subjects infected by Loa loa in response to
      antigens of several parasitic stages were compared with those from
      amicrofilaraemic (Mf-) individuals. While a strong lymphoproliferative response
      and consistent levels of both Th1 (IL-2, interferon-gamma (IFN-gamma)) and Th2
      (IL-4, IL-5) type cytokines were observed in response to adult worm (AW) and
      microfilariae (Mf) antigen in Mf- individuals, Mf+ subjects were characterized by
      a T cell unresponsiveness, including proliferation, cytokine production and IL-2
      mRNA expression. Conversely, T cell responsiveness to mitogens and non-specific
      antigen were similar in the two endemic populations. Depletion of lymphocyte
      subpopulations indicated that T CD4+ were mainly involved in the specific
      cellular response. In contrast to other cytokines, IL-10 was produced in response
      to all parasitic stages, in both Mf+ and Mf- patients. Neutralization of IL-10
      did not restore cytokine production in Mf+ patients, while B7 mRNA expression was
      similar between Mf+ and Mf- subjects in response to Mf antigen, suggesting that
      IL-10 was not the only factor responsible for T cell unresponsiveness. Mf+
      patients have lower Mf antigen-specific IgG levels compared with Mf-, and there
      is a significant correlation between Mf antigen-specific antibodies and IL-5
      responses. These findings suggest that Mf- status is correlated with T helper
      responsiveness, including proliferation and production of both Th1- and Th2-type
      cytokines, whereas Mf+ status is characterized by unresponsiveness of the same
      cell population, induced and/or maintained by microfilariae.

PMID- 9158096
TI  - Measles virus induces apoptotic cell death in lymphocytes activated with phorbol
      12-myristate 13-acetate (PMA) plus calcium ionophore.
AB  - Peripheral blood mononuclear cells (PBMC) and T lymphocytes were infected with
      measles virus (MV) and cultured with a protein kinase C (PKC) activator, PMA and
      a calcium ionophore, ionomycin. After stimulation, cell viability and
      incorporation of 5-bromo-2'- deoxyuridine (BrdU) were decreased in MV-infected
      cells compared with mock-infected cells. DNA content analysis and terminal
      deoxytransferase (TdT)-mediated dUTP nick end labelling demonstrated that the
      hypodiploid fraction and DNA fragmentation were increased in MV-infected, T
      lymphocytes activated with PMA plus ionomycin. These data suggest that MV induces
      apoptotic cell death in cells activated by PMA plus ionomycin. In contrast to
      stimulation with PMA plus ionomycin, mitogenic stimulation with
      phytohaemagglutinin (PHA) did not induce apoptotic cell death in MV-infected
      cells, although cell proliferation was suppressed. Apoptosis induced in
      stimulated, MV-infected cells may be one mechanism of immunosuppression.

PMID- 9158098
TI  - Chloroquine self-treatment and clinical outcome of cerebral malaria in children.
AB  - Chloroquine is widely used as self-medication for presumptive treatment of
      malaria despite the existence of parasite resistance to the drug. Recent studies
      suggest that tumour necrosis factor-alpha (TNF-alpha) overproduction probably has
      a causal association with poor outcome in cerebral malaria. In addition,
      chloroquine has been shown to have inhibitory action on TNF-alpha synthesis. The
      present study aimed at evaluating chloroquine/TNF-alpha interaction in 90
      children hospitalized for severe malaria in a malaria-endemic zone. TNF-alpha and
      chloroquine varied in the same range on admission, but there was an inverse
      correlation between the two: the higher the chloroquine level, the lower the TNF
      alpha level. Parasite resistance to chloroquine in vitro was high. The clinical
      course in the patients was uneventful, save for two fatal cases and one survivor
      with neurological sequela. The above data suggest beneficial effects of
      chloroquine self-medication with respect to anti-TNF-alpha action. Rational use
      of this tool should be encouraged.

PMID- 9158099
TI  - Human T cell responses to recombinant mite antigens of Dermatophagoides farinae.
AB  - We studied T cell responses to four glutathione S transferase (GST)-fused mite
      antigens prepared in our laboratory using peripheral blood lymphocytes from mite
      sensitive patients with bronchial asthma. Of the four recombinant antigens,
      purified GST-Mag3 had the strongest ability to cause patients' lymphocytes to
      proliferate, and its potency was almost comparable to that of crude mite bodies
      (Dfb) and faeces (Dff) antigens and a purified major antigen, Der f 2. The
      responder lymphocytes were mainly T cells, because the proliferative response was
      depleted by the treatment of lymphocytes with anti-CD3 antibody and complement,
      but not with anti-CD20 antibody and complement. The responsiveness of lymphocytes
      to GST-Mag3 correlated with that to Der f 2, but GST-Mag3 displayed slightly
      higher activity to stimulate lymphocytes than Der f 2. Simultaneously, the levels
      of Dff- and GST-Mag3-specific IgE antibodies correlated with the responsiveness
      of lymphocytes to GST-Mag3. These results suggest that Mag3 is a new valuable
      antigen for the response of T cell proliferation in mite-sensitive patients.

PMID- 9158100
TI  - Increased levels of IL-13 mRNA, but not IL-4 mRNA, are found in vivo in
      peripheral blood mononuclear cells (PBMC) of patients with atopic dermatitis
      (AD).
AB  - Previous studies using in vitro systems with various stimuli have shown that PBMC
      from patients with AD show increased levels of IL-4 but decreased levels of
      interferon-gamma (IFN-gamma) compared with PBMC from normal controls. However, in
      vitro conditions do not always mimic the in vivo condition. We therefore believe
      that it is important to quantify the expression of these cytokines in freshly
      isolated PBMC. This study examines the expression of IFN-gamma, IL-4 and IL- 13
      mRNA in freshly isolated PBMC from adult patients with AD, from patients with
      psoriasis vulgaris and from healthy adults, using the semiquantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR) method. Levels of IFN-gamma mRNA
      were significantly lower in PBMC of patients with AD than in controls. IL-4 mRNA
      levels did not differ significantly between groups. Conversely, levels of mRNA
      for IL-13 were significantly greater in PBMC of patients with AD than in
      controls. An increase in IL-13 expression may regulate the in vivo synthesis of
      IgE in patients with AD.

PMID- 9158101
TI  - Induction of human IgE synthesis in B cells by a basophilic cell line, KU812.
AB  - Induction of human IgE synthesis in B cells requires, in addition to IL-4 or IL
      13, a second signal provided by CD40 ligand (CD40L) on activated Th2-type CD4+ T
      cells that do not or weakly express Fas ligand (FasL). Mast cells and basophils
      also produce IL-4 or IL-13 and express CD40L after immunologic or pharmacologic
      stimulation, although it is unknown whether these cells express FasL. This study
      investigated the capacity of KU812 cells, a human basophilic cell line, to
      produce IL-4 and IL-13, to express CD40L and FasL, and to induce IgE and IgG4
      synthesis in human normal B cells. Upon stimulation of KU812 cells with either
      phorbol myristate acetate (PMA) or ionomycin (Iono), IL-4, but not IL-13, was
      produced in response to Iono, while IL-13, but not IL-4, was inducible by PMA.
      Moreover, both the time courses of IL-4 and IL-13 production and their amounts
      secreted were different; IL-4 production was transient, IL-13 production
      gradually increased, and IL-13 was heavily secreted as compared with IL-4. The
      combination of PMA and Iono (PMA/Iono) induced higher production of IL-4 or IL-13
      than did Iono or PMA alone. KU812 cell-derived IL-4 and IL-13 had the ability to
      cause CD23 expression on B cells. PMA/Iono also up-regulated CD40L expression and
      induced a very low level expression of FasL. KU812 cells that had been activated
      by PMA/Iono followed by fixation could induce IgE and IgG4 synthesis in B cells
      in the presence of recombinant IL-4 or IL-13. This contact-dependent induction of
      IgE was completely abrogated by adding anti-CD40L MoAb or soluble CD40, whereas
      anti-FasL antibody did not significantly affect IgE production. These results
      indicate that activated KU812 cells produce biologically active IL-4 and IL-13,
      express functional CD40L, and exhibit weak induction of FasL, thereby supporting
      sufficient IgE production by B cells.

PMID- 9158102
TI  - Calcium channel blockers suppress the contact hypersensitivity reaction (CHR) by
      inhibiting antigen transport and presentation by epidermal Langerhans cells in
      mice.
AB  - Since Langerhans cells (LC) are the principal antigen-presenting cells among
      epidermal cells, treatments suppressing LC function may inhibit CHR. Although
      calcium channel blockers (CCB) have been shown to suppress the functions of
      several immunologically active cells, little is known about their effect on LC.
      In this study we show that pretreatment with topical 1% nifedipine or verapamil
      HCl significantly suppressed both the sensitization and elicitation phases of a
      CHR in mice. We then investigated whether CCB affected LC. Flow cytometric
      analysis of regional lymph node cells obtained 24 h after applying FITC
      demonstrated that topical CCB treatment significantly reduced the percentage of
      FITC+ NLDC-145+ cells, suggesting that CCB had suppressed antigen transport by
      LC. In vitro treatment with nifedipine or verapamil significantly suppressed the
      antigen-presenting capacity of LC in a dose-dependent manner. In addition, in
      vitro CCB treatment reduced the percentage of class II MHC antigen-positive
      epidermal cells and significantly suppressed class II MHC and B7-1 levels in LC,
      as determined by flow cytometry and reverse transcriptase-polymerase chain
      reaction, whereas surface expression of B7-2 and mRNA was only weakly reduced.
      Neither expression of CD45 nor the percentage of CD45+ cells were affected,
      suggesting that the effects of CCB on LC were not due to cytotoxicity. Our
      results suggest that CCB inhibit CHR, at least in part, by suppressing the
      functions of LC.

PMID- 9158103
TI  - Adhesion molecule expression in vivo on extraocular muscles (EOM) in thyroid
      associated ophthalmopathy (TAO).
AB  - TAO is an autoimmune condition characterized by mononuclear cell infiltration of
      the extraocular muscles (EOM) and/or the orbital fat/connective tissue with
      associated deposition of glycosaminoglycans (GAG) in the interstitial spaces. In
      this study, the presence and distribution of the vascular adhesion molecules
      intercellular adhesion molecule-1 (ICAM-1), endothelial-leucocyte adhesion
      molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1) and the leucocyte
      integrins CD11a/CD18, CD11b/CD18, CD11c/CD18 were investigated. Nineteen EOM
      biopsies were collected from 17 patients with early (n = 6) and late (n = 13) TAO
      as well as from 12 non-TAO control patients. Consecutive cryostat sections of
      these biopsies were immunostained with MoAbs to the above-mentioned molecules and
      haematoxylin and eosin. Primary antibody binding was visualized using an avidin
      biotin system. In early untreated TAO specimens, the interstitial and perimysial
      connective tissue surrounding EOM fibres and numerous mononuclear cells stained
      strongly for ICAM-1. In contrast, the vascular endothelial cells (ulex lectin
      positive) stained strongly for ELAM-1 (E-selectin), VCAM-1 as well as ICAM-1. In
      late disease, the same distribution of immunoreactivity for ICAM-1, ELAM-1 and
      VCAM-1 was observed, but with significantly lower staining. The leucocyte
      integrins (CD11a, CD11b, CD11c) were again expressed at significantly higher
      levels in early TAO specimens compared with late TAO specimens and were minimal
      or absent in the EOM biopsies harvested from control patients. In conclusion,
      increased expression of adhesion molecules studied correlated with early active
      disease and was reduced in later stages.

PMID- 9158104
TI  - IL-1 receptor antagonist inhibits recurrence of disease after syngeneic
      pancreatic islet transplantation to spontaneously diabetic non-obese diabetic
      (NOD) mice.
AB  - The effect of an IL-1 receptor antagonist on recurrence of hyperglycaemia after
      syngeneic pancreatic islet transplantation to spontaneously diabetic female NOD
      mice was investigated. The transplanted animals were treated with either the
      receptor antagonist (8.0 mg/kg body weight per day for 12-14 days) or PBS,
      delivered by subcutaneously implanted osmotic pumps. In the control animals, a
      transient normoglycaemia was achieved, but hyperglycaemia was generally observed
      6 days after islet transplantation. Administration of IL-1 receptor antagonist
      had a clear protective effect against recurrence of hyperglycaemia until day 14,
      but after cessation of drug delivery hyperglycaemia re-appeared. The results
      indicate that continuous administration of the IL-1 receptor antagonist can
      prevent recurrence of the diabetogenic process in NOD mice. IL-1 receptor
      antagonist may therefore become a useful adjuvant immunomodulating therapy after
      human islet transplantation in insulin-dependent diabetes mellitus.

PMID- 9158105
TI  - Up-regulation of macrophage colony-stimulating factor (M-CSF) and migration
      inhibitory factor (MIF) expression and monocyte recruitment during lipid-induced
      glomerular injury in the exogenous hypercholesterolaemic (ExHC) rat.
AB  - Although macrophages play an important role in lipid-induced glomerular injury,
      we know little of the mechanisms by which hyperlipidaemia induces monocyte
      recruitment. This study investigated the role of M-CSF and macrophage MIF in
      monocyte recruitment during the development of lipid-induced glomerular injury in
      the susceptible ExHC rat strain. Groups of five ExHC rats were fed a high
      cholesterol diet (HCD) containing 3% cholesterol, 0.6% sodium cholate and 15%
      olive oil, and killed after 3 days, 1, 2 or 6 weeks. Control animals were killed
      on day 0 or after 6 weeks on a normal diet. Animals were hypercholesterolaemic 3
      days after the induction of the HCD, but showed no change in plasma triglycerides
      over the 6-week period. Glomerular macrophage accumulation was first evident at 1
      2 weeks and increased up to week 6, when macrophage-derived foam cells were seen
      in almost all glomeruli, and segmental lesions and mild proteinuria were also
      evident. Combined in situ hybridization and immunohistochemistry staining
      demonstrated that, coincident with the induction of hypercholesterolaemia on day
      3, there was marked up-regulation of M-CSF and MIF mRNA expression by intrinsic
      glomerular cells (mostly mesangial cells and podocytes) which preceded monocyte
      recruitment. There was a highly significant correlation between the number of M
      CSF and MIF-positive cells and glomerular macrophage accumulation over the 6-week
      period. Although some glomerular macrophages and foam cells exhibited M-CSF and
      MIF expression, the major source of these molecules was intrinsic glomerular
      cells. No local macrophage proliferation was observed during the development of
      glomerular lesions. In conclusion, hypercholesterolaemia caused marked up
      regulation of M-CSF and MIF expression by intrinsic glomerular cells, which
      correlated with monocyte recruitment and the development of lipid-induced
      glomerular injury. This is the first study to implicate local synthesis of MIF in
      the pathogenesis of lipid-induced lesions.

PMID- 9158106
TI  - Effective treatment of experimental lupus nephritis by combined administration of
      anti-CD11a and anti-CD54 antibodies.
AB  - Mice with chronic graft-versus-host disease (GVHD), induced by injection of DBA/2
      lymphocytes in (C57BL10*DBA/2) F1 hybrids, develop a syndrome resembling systemic
      lupus erythematosus (SLE) with immune complex glomerulonephritis. In this model
      we evaluated the role of interactions between CD11a (LFA-1alpha) and CD54
      (intercellular adhesion molecule-1 (ICAM-1)) molecules on leucocytes in the
      development of renal disease in systemic autoimmunity. Two weeks after induction
      of GVHD, when anti-nuclear autoantibodies were detected in the circulation and
      immune complexes had formed in the glomeruli, mice were injected twice per week
      with rat anti-CD11a and anti-CD54 MoAbs, or with their vehicle PBS, or with
      control rat IgG. MoAb treatment significantly lowered albuminuria and increased
      survival compared with control mice with GVHD. In the glomeruli of MoAb-treated
      mice there was markedly less binding of immunoglobulin and C3, while anti-renal
      tubular epithelium autoantibodies, but not anti-glomerular basement membrane
      autoantibodies, were significantly lowered in the circulation 4 weeks after
      disease induction. In addition, MoAb treatment inhibited the glomerular influx of
      CD11a+ cells and decreased development of histological abnormalities in the
      kidneys. Both rat IgG- and MoAb-treated mice developed anti-rat immunoglobulin
      antibodies. Furthermore, a marked splenomegaly with an increase of the T cell
      compartment was observed in MoAb-treated mice with GVHD. These results show that
      CD11a/CD54 interactions are crucial for the full-blown development of lupus
      nephritis in this model. Treatment aimed at blocking the activity of these
      molecules profoundly attenuated the development of renal disease in chronic GVHD
      even if started when first symptoms of SLE (i.e. anti-nuclear autoantibodies in
      sera and glomerular binding of immunoglobulins) were already detectable.

PMID- 9158107
TI  - Pathogenicity of human anti-platelet factor 4 (PF4)/heparin in vivo: generation
      of mouse anti-PF4/heparin and induction of thrombocytopenia by heparin.
AB  - Heparin-induced thrombocytopenia/thrombosis (HIT) is a severe thrombotic disorder
      that occurs in approximately 1% of patients treated with heparin. Affected
      patients commonly develop antibodies that recognize PF4/heparin complexes that
      may form on the surface of activated platelets and on the endothelium. However,
      it has not been established that anti-PF4/heparin antibodies are responsible for
      the clinical manifestations of HIT. To address this issue, we employed a recently
      developed model of active immunity to study the effect of IgG anti-PF4/heparin
      antibody in vivo. In previous studies we have shown that it is possible to induce
      autoimmune diseases such as systemic lupus erythematosus (SLE), anti-phospholipid
      syndrome (APS) or vasculitis in naive mice by active immunization with anti-DNA,
      anti-cardiolipin and anti-neutrophil cytoplasmic antibodies, respectively.
      Immunized animals develop anti-idiotypic antibodies (Ab2) and, after 2-4 months,
      anti-anti-idiotypic antibodies (Ab3). Ab3s generated in this manner often
      simulate the binding activity of Ab1 and their expression correlates with the
      development of specific clinical manifestations typical of the respective human
      disease. Based on this experience, naive BALB/c mice were immunized with IgG anti
      PF4/heparin antibodies isolated from two patients with HIT. The actively
      immunized mice developed mouse anti-PF4/heparin antibody (Ab3). Administration of
      unfractionated heparin, but not low molecular weight heparin (LMWH), to the
      actively immunized animals induced thrombocytopenia by day 4 of drug exposure.
      There was no evidence of thrombosis. The results of this study support the
      importance of anti-PF4/heparin antibodies in the pathogenesis of HIT. Further,
      this model may help to elucidate the factors responsible for thrombosis as well
      as providing means to assess new treatment options for patients with this
      disorder.

PMID- 9158108
TI  - Intravenous immunoglobulin (IVIG) treatment of experimental colitis induced by
      dextran sulfate sodium in rats.
AB  - We investigated the therapeutic effect and immunological action mechanism of IgG
      in experimental colitis induced by 3% dextran sulfate sodium in rats. Intravenous
      injection of homologous (rat) IgG (400 mg/kg per day) caused a significant
      suppression of occult blood discharge and ulcerative lesions in the colon, while
      no suppressive effect was observed in the case of heterologous (human) IgG. The
      positive effect of rat IgG on the lesions was also clearly shown by the
      histological examinations. Generation of proinflammatory cytokines, i.e. tumour
      necrosis factor-alpha (TNF-alpha) and IL-1alpha, in the lesions was found to be
      inhibited by administration of rat IgG. Little or no suppressive action was
      exerted by human IgG. Careful examination of recruited T cells and macrophages,
      both of which are thought to play important roles in the development of
      ulcerative colitis, indicated that rat IgG, but not its human counterpart,
      decreased the number of immunocompetent cells in colonic mucosa. Meanwhile, in an
      in vitro study, both forms of IgG were shown to suppress production of TNF-alpha
      and IL-1alpha from lamina propria mononuclear cells isolated from rat colon.
      These findings suggest that, mainly by suppressing recruitment of immunocompetent
      cells into the lesions, homologous IgG may reduce the occurrence of colitis.

PMID- 9158109
TI  - Induction of proinflammatory cytokine and antioxidant enzyme gene expression
      following brief myocardial ischaemia.
AB  - The purpose of this study was to determine if proinflammatory cytokines are up
      regulated during reperfusion following sublethal ischaemia, and whether
      concurrent up-regulation of antioxidant enzymes occurs. Open-chest rats were
      subjected to 15 min of ischaemia followed by 1 or 3 h reperfusion (R). Myocardium
      from the ischaemic zone showed a significantly higher (P<0.01) generation of
      thiobarbituric acid-reactive substances at 1 h and 3 h R. Northern blots showed a
      weak signal in controls for IL-6 mRNA (0.13 +/- 0.01); this was elevated to 0.68
      +/- 0.12 at 1 h and 0.69 +/- 0.10 at 3 h R. Neither IL-1beta nor tumour necrosis
      factor-alpha (TNF-alpha) were detectable in controls. IL-1beta rose to 0.78 +/-
      0.07 at 1 h and 0.51 +/- 0.08 at 3 h R, and TNF-alpha rose to 0.69 +/- 0.10 at 1
      h and 0.38 +/- 0.15 at 3 h R. Western blotting showed no signals in the control,
      but readily detectable signals at 1 h R; these remained high (IL-6) or decreased
      (IL-1beta and TNF-alpha at 3h R. mRNA analysis for antioxidant enzymes revealed a
      weak signal in controls for catalase (CAT; 0.16 +/- 0.08), glutathione peroxidase
      (GSH-Px; 0.15 +/- 0.06) and superoxide dismutase (SOD; 0.21 +/- 0.05). After 1 h
      R, levels increased significantly for CAT (0.46 +/- 0.10; P < 0.025) and GSH-Px
      (0.51 +/- 0.13; P < 0.01), but remained similar to controls for SOD (0.26 +/-
      0.15). At 3 h R the mRNA levels were significantly elevated for the three enzymes
      (CAT 0.48 +/- 0.13; GSH-Px 0.47 +/- 0.10; SOD 0.54 +/- 0.08). We conclude that
      mRNA for proinflammatory cytokines is expressed early in reperfusion, and that
      the proteins are present in heart tissue. Also, reperfusion is associated with
      rapid expression of genes for antioxidant enzymes, which may enhance reactive
      oxygen intermediate (ROI) scavenging.

PMID- 9158110
TI  - Specific activation of resting T cells against tumour cells by bispecific
      antibodies and CD28-mediated costimulation is accompanied by Th1 differentiation
      and recruitment of MHC-independent cytotoxicity.
AB  - Specific activation of resting lymphocytes for tumour targeting can be achieved
      by bispecific monoclonal antibodies (bi-MoAbs) with specificity for tumour
      antigens and T cell-activating antigens in combination with a costimulatory anti
      CD28 antibody. In this study we focus on the immunomodulatory function of an anti
      CD3/CA19-9 bi-MoAb in combination with a costimulatory anti-CD28 antibody which
      may result not only in antigen-specific, T cell-mediated tumour cell lysis but
      also in recruitment of other cellular effector functions. In combination with
      costimulatory anti-CD28 antibodies, resting peripheral lymphocytes could be
      activated specifically to secrete high amounts of Th1 cytokines (IL-2, interferon
      gamma (IFN-gamma)) characterizing a cellular immune response. In contrast, no IL
      4 and only low amounts of IL-10 could be detected. Furthermore, bi-MoAb-mediated
      CA19-9-specific activation of T cells was accompanied by recruitment of MHC- and
      CA19-9-independent cytotoxicity, as was determined by lysis of different CA19-9
      cell lines. This MHC-independent cytotxicity was mediated at least in part by
      activated natural killer (NK) cells, as depletion of CD16+ NK cells resulted in
      substantial decrease of cytotoxicity against CA19-9- targets. Our results
      indicate that specific activation of resting T cells with CD3-associated bi-MoAbs
      in combination with an anti-CD28 antibody leads to a Th1 differentiation pathway
      and is accompanied by recruitment of MHC-independent lymphokine-activated killer
      (LAK) cell cytotoxicity which can possibly be directed against a heterogeneous
      tumour.

PMID- 9158111
TI  - Differences in the rate of donor leucocyte migration between natural and drug
      assisted tolerance following rat liver transplantation.
AB  - The number involved in and the rate of migration of donor leucocytes into the
      following recipient organs (spleen, thymus, bone marrow, lung and mesenteric
      lymph nodes) were measured in two rat models of orthotopic liver transplantation
      (OLT) using donor-specific MHC class I antibodies. The first OLT model is one
      that does not require immunosuppression in order to achieve tolerance and
      involved the transplantation of DA (MHC haplotype, RT1a) livers into PVG (RT1c)
      recipients. The second model was one that required a 7-day (10 mg/kg) treatment
      with cyclosporin A (CsA) to achieve tolerance and used DA donors into Lewis
      (RT1(1)) recipients. Recipient organs were biopsied on days 3, 20 and 87
      following OLT and donor leucocyte migration was quantified by
      immunohistochemistry and computer densitometry of immunoblots of detergent
      solublized tissues in order to resolve both membrane-bound and soluble donor MHC
      class I antigen. In a separate experiment, spleen biopsies were taken following
      OLT on days 3 and 15 from the naturally tolerizing OLT model (DA into PVG),
      treated with and without CsA for 7 days and compared with the (DA into Lewis)
      model. The initial rate of leucocyte migration between days 3 and 21 following
      OLT was found to be the most rapid into the spleen, followed by the bone marrow
      and mesenteric lymph nodes in the naturally tolerant (DA into PVG) model when
      compared with the (DA into Lewis) model. The number of donor leucocytes in the
      spleen and mesenteric lymph nodes in both models was, however, approximately the
      same by 87 days. No real difference in the rate of leucocyte migration was seen
      in the thymus or the lung for both transplant models over the time course
      assayed. CsA was found to lower the rate of donor leucocyte migration only over
      the period it was administered. The rate of donor leucocyte migration into the
      spleen was still much lower 15 days after OLT in the (DA into Lewis) model
      compared with the (DA into PVG) model treated with and without CsA. Thus the
      differences in the rate of donor leucocyte migration into the spleen, bone marrow
      and mesenteric lymph nodes immediately following OLT may offer an explanation as
      to why the (DA into PVG) combination is able to accept a transplanted liver
      without immunosuppressive therapy.

PMID- 9158112
TI  - Somatic hypermutation of immunoglobulin genes in human neonates.
AB  - The antibody response in the young infant is limited in several ways; in
      particular, responses generally are of low affinity and restricted to IgM. This
      raises the question whether the affinity maturation process, consisting of
      somatic mutation of immunoglobulin genes coupled with selection of high-affinity
      variants, is operative in the neonate. Re-arranged V(H)6 genes were amplified by
      polymerase chain reaction (PCR) from cord blood and from peripheral blood of
      infants. Heteroduplex analysis detected mutation in only 2/18 cord blood samples,
      while mutations were seen from about 10 days of age onwards. Cloning and
      sequencing of mutated neonatal V(H)6 genes showed that mutated sequences
      contained relatively few mutations (one to three mutations per sequence) compared
      with published values of about 10 in adult IgM sequences. Selection was not
      evident in the majority of neonatal samples. Thus mutation can occur in the human
      neonate, but is minimal and generally not accompanied by selection. The age at
      which affinity maturation develops effectively is yet to be defined.

PMID- 9158114
TI  - Vascular surgery entering the twenty-first century: an FDA perspective.

PMID- 9158113
TI  - IL-12 inhibits in vitro immunoglobulin production by human lupus peripheral blood
      mononuclear cells (PBMC).
AB  - Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease
      characterized by polyclonal B cell activation and by the production of anti
      double-stranded (ds) DNA antibodies. Given the inhibitory effects of IL-12 on
      humoral immune responses, we investigated whether IL-12 displayed such an
      activity on in vitro immunoglobulin production by SLE PBMC. Spontaneous IgG,
      IgG1, IgG2, IgG3 and IgM antibody production was dramatically reduced by addition
      of IL-12. These results were confirmed by Elispot assays detecting IgG- and anti
      dsDNA-secreting cells. While IL-6 and TNF titres measured in PBMC supernatants
      were not modified by addition of IL-12, interferon-gamma (IFN-gamma) titres were
      up-regulated and IL-10 production down-regulated. Since addition of IFN-gamma did
      not down-regulate immunoglobulin production and since the inhibitory activity of
      IL-12 on immunoglobulin synthesis was not suppressed by anti-IFN-gamma antibody,
      we concluded that the effect of IL-12 on immunoglobulin production was not
      mediated through IFN-gamma. Our data also argue against the possibility that down
      regulation of endogenous IL-10 production was responsible for the effect of IL
      12. Thus, inhibition of IL-10 production by IFN-gamma was not accompanied by
      inhibition of immunoglobulin production, and conversely, restoration of IL-10
      production by anti-IFN-gamma antibody did not suppress the inhibitory activity
      exerted by IL-12 on immunoglobulin production. Taken together, our data indicate
      that reduction of excessive immunoglobulin and anti-dsDNA antibody production by
      lupus PBMC can be achieved in vitro by IL-12, independently of IFN-gamma and IL
      10 modulation.

PMID- 9158115
TI  - Cardiovascular research: an NIH perspective.

PMID- 9158116
TI  - Pathogenesis of venous thrombosis: a new insight.
AB  - Venous thrombosis and thrombophlebitis have long been observed to result in
      painful inflammation around the affected veins. The full extent of the
      synergistic interaction between thrombosis and the inflammatory response and how
      this leads to the later sequelae of chronic venous insufficiency is only now
      beginning to be understood. Venous thrombosis is known directly to elicit an
      inflammatory response in the thrombus and vein wall. Leukocytes including
      neutrophils and monocytes roll, adhere, activate and extravasate into the vein
      wall based on a vein wall cytokine/chemokine gradient producing an inflammatory
      response. Such a response leads to amplification of thrombus formation through
      mechanisms such as the elaboration of tissue factor on the surface of monocytes
      and the release of cathespin G from activated neutrophils (distrupting the
      endothelial cell barrier), exposing the thrombogenic subendothelial vein wall
      collagen. Selectins such as P-selectin and the proinflammatory cytokine tumor
      necrosis factor appear important in this vein wall response. Inhibition of
      inflammation before the initiation of the thrombotic event may decrease the
      detrimental vein wall changes that contribute to vein wall and vein valve damage
      and thrombus formation.

PMID- 9158117
TI  - Comparison of perioperative results obtained with carotid eversion endarterectomy
      and with conventional patch plasty.
AB  - After limited experience with eversion endarterectomy of the internal carotid
      artery, comparison has been made between perioperative results obtained with the
      eversion technique and with the conventional method. The perioperative results of
      715 consecutive cases of patch plasty of the internal carotid artery performed
      between January 1986 and December 1990 were reviewed and compared with
      perioperative data of 739 consecutive cases of eversion endarterectomy, performed
      between January 1991 and December 1993. The duration of surgery was also
      recorded. Statistical analysis was carried out, using chi2 test, Fisher's Z test
      and Student's t-test. The postoperative stroke rate was 2.9% in the conventional
      endarterectomy group, and 0.95% in cases of eversion endarterectomy (P<0.01); the
      stroke mortality rates were 1.8% and 0.54% respectively (P<0.05). Overall
      mortality rate was 2.9% in the conventional group and 0.95% in the eversion group
      (P<0.01): combined morbidity and mortality rate was 4% versus 1.35% (P<0.001). A
      statistically significant difference was found in favour of the eversion method
      between the duration of surgery (90.9 min versus 52.8 min; P<0.005) and between
      the mean clamp time (34.9 min versus 22.4 min: P<0.005). On the basis of these
      results, it is concluded that eversion endarterectomy of the internal carotid
      artery is a safe and rapid technique and its immediate results were superior to
      those obtained after conventional endarterectomy and patch plasty.

PMID- 9158118
TI  - Venous allografts for infrainguinal vascular bypass.
AB  - Between 1978 and 1993, 107 patients received venous allografts for infrainguinal
      revascularization because autogenous material was unavailable. These operations
      comprised 7.4% of 1442 reversed vein bypass procedures performed during the same
      period. Alloveins were harvested during varicose vein stripping and stored up to
      10 days in saline solution containing heparin and antibiotics. Veins with or
      without minimal degenerative changes were used and when necessary segments were
      sutured end-to-end to obtain a convenient length. The patients comprised 95 men
      and 12 women of age range 44-87 years. All operations were performed for limb
      salvage (rest pain and gangrene); 40 femoropopliteal and 67 femorocrural bypasses
      were performed; 66 were primary reconstructions and 41 secondary reconstructions.
      The operative mortality rate was 3.7%. Early thrombosis occurred in 18 patients
      (16.8%), nine of whom were successfully reoperated upon. The cumulative patency
      rates for all bypass operations was 82.9%, 38.7% and 21.3% at 30 days, 3 and 5
      years, respectively, the limb salvage rates being 84.8%, 48.0% and 29.2%,
      respectively. Allografts may have a place in lower-limb bypass surgery in the
      absence of veins, polytetrafluoroethylene or human umbilical vein.

PMID- 9158119
TI  - Racial differences in operation for peripheral vascular disease: results of a
      population-based study.
AB  - Operation for non-coronary atherosclerotic peripheral vascular occlusive disease
      may vary among race and gender groups. Using a state-wide registry, the authors
      identified all operations performed for infrarenal peripheral vascular disease
      over a 12-month period in a single south-eastern state. Procedures performed
      included reconstruction for aortoiliac (n=641) and infrainguinal (n=1129) disease
      and major amputation (n=1077). The incidence for patients over age 50 was
      calculated using census data. Operation for aortoiliac disease was significantly
      more likely for white patients (relative risk 3.79, 95% C.I. 2.84-5.15), but less
      likely for infrainguinal peripheral vascular disease (relative risk 0.64, 95%
      C.I. 0.56-0.73) and amputation (relative risk 0.17, 95% C.I. 0.15-0.19). Trends
      toward lower operative mortality in blacks with aortoiliac disease (10.6% versus
      12.0%), PVD (3.2% versus 3.5%), and amputation (5.5 versus 8.7%) failed to attain
      statistical significance. Patient race was associated with the type and location
      of operation performed for peripheral vascular disease.

PMID- 9158120
TI  - An acute phase reaction in diabetic patients with foot ulcers.
AB  - The acute phase reaction is a molecular response to noxious stimuli. Over 50
      glycoproteins have been identified as reactants. While this is likely a
      protective response, some of the changes could be detrimental to body
      homeostasis. The objective of this study was to examine whether an acute phase
      reaction occurs in diabetic patients with foot ulcers. In age- and sex-matched
      populations, measurements of C-reactive protein, fibrinogen, albumin, hematocrit,
      whole blood viscosity and protein C were performed on: (i) 24 diabetic patients
      with a foot ulcer (group A); (ii) eight diabetic patients without foot ulcer
      (group B); and (iii) seven patients without diabetes (group C). Analysis of
      variance was used to compare means of each respective group (mean (s.d.)). Group
      A demonstrated an increase in C-reactive protein (5.6 (5.4) mg/dl) compared with
      group B (0.78 (0.46) mg/dl; P = 0.013) and group C (0.71 (0.26) mg/dl; P =
      0.026). Fibrinogen was also increased in group A (619 (205) mg/dl) compared with
      group B (310 (58) mg/dl; P = 0.005) and group C (370 (88) mg/dl; P = 0.04).
      Hematocrit (37 (6)%) and albumin (3.5 (0.5) g/dl) were decreased in group A
      compared with group B (hematocrit 46 (4)%; P < 0.0001; albumin 4.3 (0.3) g/dl; P
      = 0.0005) and group C (hematocrit 45 (3)%; P = 0.005; albumin 4.6 (0.3) g/dl; P <
      0.0001). No difference was found in whole blood viscosity and levels of protein
      C. There also was no significant difference demonstrated between any of the
      parameters studied when comparing groups B and C. In conclusion, these results
      indicate that diabetic patients with a foot ulcer undergo an acute phase reaction
      as evidenced by a rise in C-reactive protein and fibrinogen compared with
      diabetic patients without a foot ulcer and normal control patients. As more is
      learned about the acute phase reaction, this information may prove valuable in
      the management of the diabetic patient.

PMID- 9158121
TI  - Popliteal artery war injuries.
AB  - The early postoperative results of 44 surgically treated popliteal arterial
      injuries from the Yugoslav civil war are reported. Of these patients, 41 (93%)
      were males and three (7%) were females, average age was 28 (range 6-45) years.
      Twenty patients (45%) had gunshot wounds and 24 (55%) explosive wounds. Twelve
      (28%) suffered isolated vascular damage, while 32 (72%) suffered concomitant bone
      fractures. Isolated arterial lesions were found in 24 (55%) cases, and
      concomitant arterial and venous lesions in 20 (45%). Twenty-four (55%) had
      primary reconstructions after haemostasis in the initial war hospital, and 20
      (45%) secondary reconstructions after inadequate primary reconstruction in a
      regional war hospital. Artery procedures included 19 reverse saphenous vein graft
      interpositions, 10 reverse saphenous vein bypasses, 12 'in situ' saphenous vein
      bypasses and five lateral subcutaneous saphenous vein bypasses. The early graft
      patency rate was 100%, and limb salvage 72%. Major amputation was performed in
      28%. Concomitant bone fractures, secondary reconstructions, secondary haemorrhage
      from an infected graft, and explosion wounds significantly increased the
      amputation rate (P < 0.01). Eleven amputations were performed after an anatomic,
      and only one after an extra-anatomic reconstruction (P < 0.01). The authors
      recommend an in situ or lateral subcutaneous reconstruction in cases of
      complicated popliteal artery injuries, such as concomitant bone fractures
      accompanied by massive soft tissue damage, and this type of reconstruction should
      also be used if infection is present or the procedure is delayed.

PMID- 9158122
TI  - Artery wall damage and platelet uptake from so-called atraumatic arterial clamps:
      an experimental study.
AB  - A 'traumatic' clamps are routinely used to control arteries during
      reconstruction, but little is known about the arterial damage caused and the
      effects on platelet uptake. This experiment used sheep carotid arteries to
      correlate the degree of histologic damage observed with the level of indium-111
      labelled platelet uptake in clamped arterial segments. Scanning electron
      microscopy and light microscopy enabled three degrees of injury to be recognized.
      In mild injuries, endothelial cell orientation was changed but local platelet
      uptake was little different from controls. In moderate injuries, the endothelial
      cells directly squeezed by the clamp were morphologically altered, superficial
      fissures developed which extended into the media, and local platelet uptake was
      usually increased. Severe injuries caused extensive endothelial cell
      desquamation, formation of deep cavities in the media and increased platelet
      uptake (mean 5.51 times that of control). Platelet uptake at the site of clamp
      application was not significantly different from non-clamped carotids for mild
      injuries. However, the increased platelet uptakes for moderate (P = 0.007) and
      severe (P = 0.005) injuries were statistically significant when compared with non
      clamped control arterial segments.

PMID- 9158123
TI  - Traumatic first rib fracture: is angiography necessary? A review of 730 cases.
AB  - The two most common sites of first rib fracture were at the subclavian sulcus and
      in the neck of the first rib, posteriorly. Five distinct mechanisms for rib
      fracture were identified and included: (i) posteriorly directed trauma to the
      upper thorax or shoulder girdle; (ii) a direct blow to the sternum and anterior
      chest wall; (iii) a blow fracturing the clavicle; (iv) a strong sudden
      contraction of the scalenus anticus muscle; and (v) radiographic findings of a
      first rib fracture without history of trauma. Isolated first rib fracture
      regardless of mechanism of injury, results in a low incidence of major vascular
      injury (mean 3%), although with fracture displacement, the incidence is higher.
      First rib fracture associated with concomitant head, thoracic, abdominal, or long
      bone trauma was associated with vascular injury in 24% of cases. According to
      this review, specific indications for subclavian artery and aortic arch
      arteriography in patients with traumatic first rib fracture include widened
      mediastinum on chest radiography, upper-extremity pulse deficit, posteriorly
      displaced first rib fracture, subclavian groove fracture anteriorly, brachial
      plexus injury and expanding hematoma.

PMID- 9158125
TI  - Endoluminal pulse oximetry combined with tonometry to monitor the perfusion of
      the sigmoid during and after resection of abdominal aortic aneurysm.
AB  - Early detection of colonic ischaemia after aortic grafting is essential if
      mortality is to be decreased when this complication develops. The aim of this
      study was to determine changes in the sigmoid colon during and after abdominal
      aortic grafting using endoluminal pulse oximetry (SmO2). Oxygen saturation was
      measured on the mucosa (SmO2) and serosa (SsO2) of 20 sequential patients
      undergoing elective surgery for abdominal aortic aneurysm; intramural pHi was
      also measured. Initially, all patients had a normal SmO2 in the sigmoid; however,
      before cross-clamping eight patients had a reduction in the SmO2. The pulse curve
      disappeared immediately after cross-clamping in 15 patients, with only five still
      showing a pulse curve in the sigmoid colon. Before declamping, 13 patients
      regained their pulse curve. The intraluminal pHi showed a large interindividual
      variation (2 S.D. approximately 0.4). Patients were classified into three groups
      according to SmO2: group A, no pulse; group B, diminished saturation (< 90%); and
      group C, normal saturation (> or = 90%). There was significant correlation with
      the pHi after cross-clamping in all groups. One patient who developed ischaemia
      of the sigmoid colon demonstrated a prolonged reduction in the SmO2, a decreased
      perioperative pHi, and an increased oxygen saturation in the inferior mesenteric
      vein during cross-clamping.

PMID- 9158124
TI  - Cardiac risk assessment before vascular surgery: a prospective study comparing
      clinical evaluation, dobutamine stress echocardiography, and dobutamine Tc-99m
      sestamibi tomoscintigraphy.
AB  - Preoperative evaluation for cardiac risk assessment before peripheral vascular
      surgery remains controversial. Between January and June 1994, a prospective open
      study was carried out in 156 patients scheduled for elective vascular procedures
      (63 carotid endarterectomies, 34 abdominal aortic aneurysms, 29 aortoiliac and 30
      infrainguinal reconstructions) to compare the ability of clinical data,
      dobutamine stress echocardiography, and dobutamine Tc-99m sestamibi
      tomoscintigraphy to predict postoperative cardiac events. Pharmacological stress
      testing consisted of incremental dobutamine infusion (+/-1 mg atropine to achieve
      85% of age-predicted maximal heart rate, with continuous echocardiographic
      monitoring, and injection of Tc-99m sestamibi after dobutamine infusion).
      Dobutamine echocardiography was abnormal in 36 patients (worsening resting wall
      motion abnormality in 11; new induced wall motion abnormality in 25). Dobutamine
      Tc-99m sestamibi tomoscintigraphy revealed a reversible perfusion defect in 34
      patients, indicating the presence of myocardial ischaemia. As a result, eight
      patients underwent myocardial revascularization (n = 5) or the proposed operation
      was cancelled (n = 3). In the remaining 142 vascular procedures, there were eight
      (5.6%) adverse cardiac events: three myocardial infarctions (two fatal), three
      prolonged myocardial ischaemia, one acute congestive heart failure and one
      sustained ventricular arrhythmia in the post operative period. Univariate
      analysis selected unstable angina (relative risk (RR) 11.6), previous congestive
      heart failure (RR 6.4), Detsky's score of > or = 15 (RR 3.0), positive dobutamine
      stress echocardiography (RR 3.7), and positive dobutamine tomoscintigraphy (RR
      7.4) as significant predictors of postoperative cardiac events. In patients
      without clinical markers of coronary artery disease (n = 66), non-invasive
      cardiac testing did not predict cardiac complications (n = 2; one prolonged
      myocardial ischaemia; one infarction). In the subset of 76 patients with definite
      clinical or electrocardiographic evidence of ischaemic heart disease, dobutamine
      stress testing provided additional information, and optimized risk
      stratification: five of six patients who suffered a cardiac complication had a
      pathologic dobutamine stress test. Furthermore, a negative dobutamine stress test
      was characterized by a high negative predictive value (0.96 for echocardiography;
      0.97 for tomoscintigraphy). The study further demonstrated that the cardiac
      response (ischaemic versus non-ischaemic) to dobutamine stress was concordantly
      classified by echocardiographic and tomoscintigraphic techniques in 96% of cases.
      It is concluded that complementary non-invasive cardiac stress testing by
      dobutamine is indicated only in patients with clinically apparent coronary artery
      disease.

PMID- 9158126
TI  - Comparison of transperitoneal and retroperitoneal approaches for infrarenal
      aortic surgery: early and late results.
AB  - The retroperitoneal approach to the infrarenal aorta was purported to have a
      shorter recovery and reduced degree of surgical stress than the transperitoneal
      approach. Hence, this study aimed to determine any advantages of one approach
      over the other. One hundred patients undergoing infrarenal aortic surgery between
      1989 and 1992 were randomized to the transperitoneal or retroperitoneal approach;
      64 operations were for aneurysms (32 transperitoneal, 32 retroperitoneal) and 36
      for occlusive disease (18 transperitoneal, 18 retroperitoneal). Parameters
      monitored were operating time, cross-clamp time, blood loss, fluid requirement in
      first 24 h, analgesia requirements, gastrointestinal function, morbidity,
      mortality and length of stay in intensive care and hospital. A minimum 3-year
      follow-up was obtained to assess mortality and wound problems. Inter-group
      demographic data were comparable. There was no significant difference between the
      two approaches for: operating time 190 versus 202 min, P = 0.26); cross-clamp
      time (72 versus 81 min, P = 0.93); blood loss (1095 versus 1072 ml, P = 0.56); 24
      hour fluid requirements (6900 versus 7000 ml, P = 0.45); analgesia requirements
      (60 versus 55 mg, P = 0.37), gastrointestinal function, morbidity (P = 0.75),
      mortality, and length of stay in intensive care (2 versus 2 days, P = 0.80) and
      hospital (10.5 versus 10 days, P = 0.76). In the long term there were
      significantly more wound problems (bulging, hernias and wound pain) in the
      retroperitoneal group. Long-term mortality was similar in both groups.

PMID- 9158127
TI  - Pulmonary embolism: diagnosis, incidence and implications.
AB  - The purpose of this study was to determine the prevalence of pulmonary embolism
      at an academic tertiary care center, to identify the methods of diagnosis, and to
      characterize the outcomes for this population. A retrospective analysis of
      multiple data sources including records from the Medical Information System, and
      the Departments of Pathology, Radiology, Nuclear Medicine and Pharmacy were
      reviewed for all patients with positive reports of pulmonary embolism. These were
      verified by the medical records and a listing of all positive cases was
      developed. A total of 320 patients developed pulmonary embolism during the study
      period and 121 died before discharge. The prevalence was 3.5 cases per 1000
      admissions, with a mortality of 1 per 1000 cases. Significant misclassification
      of patients and errors in rate estimation would have occurred if multiple sources
      of information were not used. Definitive diagnosis and appropriate treatment with
      a Greenfield filter was associated with improved early survival. By relying on
      ICD-9 coding, 80% of fatalities and 13% of patients with positive angiograms
      would have been missed.

PMID- 9158128
TI  - The morphology of venovenous bypass graft endothelium.
AB  - Venovenous bypass grafts are commonly used in the repair of vascular trauma to
      large- and small-caliber veins. This study examines the morphology of the venous
      wall in an experimental model of the venovenous bypass graft. The morphology of
      the venous endothelium from unmanipulated jugular veins and from jugular veins
      implanted as a venovenous bypass graft in the external jugular venous system for
      10 min, 6 h, and 1, 3, 5, 7 and 28 days was examined. Veins and venovenous grafts
      were pressure fixed in situ at 80 mmHg and were examined by scanning and
      transmission electron microscopy. The endothelial cell lining remained confluent
      and intact over the 28-day period with evidence of endothelial cell contraction
      (spindle-shaped cells) for the first 72 h. Pinocytotic activity in endothelial
      cells and underlying smooth muscle cells was observed throughout the study,
      strongly indicating physiologically active cells. There was some accumulation of
      blood cells, predominantly polymorphonuclear leukocytes on the endothelial
      surface. Polymorphonuclear leukocytes were observed to infiltrate into the
      subendothelium through endothelial cell junctions within 6 h but by day 3, none
      was noted in the subendothelial space. There was no major disruption of the graft
      wall at any time point. By day 28, there was evidence of intimal thickening in
      the venovenous bypass grafts but no well-demarcated intimal hyperplasia. This
      study shows that there is no significant endothelial injury in the venovenous
      bypass grafts and that the endothelial cells remain physiologically active. Short
      term failure of venovenous bypass grafts, therefore, appears not be due to
      significant endothelial cell damage in the graft.

PMID- 9158129
TI  - Thromboxane A2 receptor density increases during chronic exposure to thromboxane
      A2 receptor antagonists after porcine carotid bypass.
AB  - Domestic swine (n=12 in each group) were randomized to daily treatment with the
      thromboxane A2 (TXA2) receptor antagonist BMS-180291 (group I), aspirin (group
      II), or no drug (group III) prior to prosthetic carotid graft implantation.
      Platelet and arterial wall receptor density were measured by equilibrium binding
      using 125I-BOP. At 6 weeks, means (s.e.m.) platelet receptor density (pmol/mg)
      had increased in groups I (3.3(0.6) versus 1.8(0.3); P<0.05) and II (2.6(0.6)
      versus 1.7(0.2); P<0.05), but not in group III (1.3(0.3) versus 1.2(0.2)). Aortic
      membrane TXA2 receptor density (fmol/mg) was significantly greater (P<0.05) in
      groups I (150(50)) and II (68(10)) compared with group III (39(6)). Chronic
      exposure to a TXA2 receptor antagonist or aspirin is associated with increased
      platelet and aortic receptor density in pigs.

PMID- 9158130
TI  - Surgery of descending thoracic aortic aneurysms with centrifugal pump support.
AB  - Fifty-five patients with descending thoracic aortic aneurysms were operated upon
      between October 1987 and October 1994. All patients were supported by a
      centrifugal pump during operation. The mean(s.d.) duration of cross-clamping was
      39(13) min. In order to evaluate the efficacy of the centrifugal pump,
      haemodynamic and metabolic measurements were made on four occasions (before cross
      clamping, immediately after cross-clamping and before cross-clamp removal) and
      again after cross-clamp removal. The haemodynamic data remained stable throughout
      the procedure: central venous pressure (15(4.6) versus 16(4.8) versus 16(4.6)
      versus 15(4.6) mmHg; P = n.s.), pulmonary artery pressure (25(6.2) versus 24(5.1)
      versus 22(5.3) versus 23(4.4) mmHg; P = n.s.), radial systolic pressure
      (119(19.9) versus 116(25.2) versus 111(25.9) versus 111(20.7) mmHg; P = n.s.) and
      heart rate (75(12.6) versus 77(14) versus 76(15.6) versus 78(16) beats/min; P =
      n.s.). The acid-base status deteriorated slowly during surgery. Values before and
      after cross-clamping were: pH (7.42 (0.04) versus 7.37(0.06); P < 0.05), base
      excess (-0.67(2.20) versus -3.70(2.50); P < 0.05) and bicarbonates (24(8.9)
      versus 20(1.9); P < 0.05). The cerebrospinal fluid pressure remained constant:
      20(5.7) versus 19(5.9) versus 18(5) versus 19(5) mmHg; P = n.s. Renal function,
      measured before, and at 1, 3 and 7 days after the operation also remained stable
      (creatinine: 1.1(0.4) versus 1.2(0.4) versus 1.2(0.4) versus 1.2(0.4); P = n.s.;
      blood urea nitrogen: 46(18.7) versus 46(18.6) versus 51(24.9) versus 55(27.9); P
      = n.s.). Step-wise multiple linear regression comparing cerebrospinal fluid
      pressure against haemodynamic and metabolic data showed that during aortic cross
      clamping there was a significant relationship between central venous pressure (P
      < 0.0013) and arterial pH (P < 0.0148), while before and after cross-clamping
      multivariate analysis showed a relationship only between central venous pressure
      and cerebrospinal fluid pressure (P < 0.0035). The results confirm that
      centrifugal pump support is effective in stabilizing haemodynamics and protecting
      the kidney during thoracoabdominal aneurysm repair.

PMID- 9158131
TI  - Surgical management of type A aortic dissection: evaluation of predisposing
      factors for postoperative neurologic complication and late reoperation.
AB  - The technique of cerebral protection during hypothermic circulatory arrest
      remains controversial. Forty-seven patients underwent operations for type A
      aortic dissection in the past 9 years. During hypothermic circulatory arrest,
      selective cerebral perfusion and retrograde cerebral perfusion was applied in 12
      and seven patients, respectively. The mortality rate was 28.6% in patients
      without adjunctive cerebral perfusion, 25.0% in selective cerebral perfusion
      patients, and zero in the retrograde cerebral perfusion group (P > 0.05).
      However, there was no mortality by cerebral injury in cerebral perfusion groups
      (P = 0.03). Age (P = 0.001), hypothermic circulatory arrest time (P = 0.012), and
      acuity (P = 0.013) were predisposing factors for cerebral injury, but cerebral
      perfusion has not yet been found to be a protective factor (P = 0.56). Nine late
      reoperations and three deaths occurred during the follow-up period. Marfan
      syndrome was the only predisposing factor for late reoperation (P = 0.016). In
      summary, although further studies are still required, retrograde cerebral
      perfusion is a possible cerebral protective factor. In addition, periodic follow
      up is mandatory, especially in patients with Marfan syndrome.

PMID- 9158132
TI  - Operative risks of the maze procedure associated with mitral valve surgery.
AB  - Twelve patients were operated on for mitral valve disease with concomitant
      chronic atrial fibrillation. Valve repair was performed in five patients and
      replacement in seven. Maze I and maze III procedures were applied in eight and
      four patients, respectively, and are compared. There was a regular rhythm in all
      maze I patients with a constant junctional rhythm in three and an alternating
      sinus and junctional rhythm in the remainder. In one case, part of the left
      atrium was in atrial fibrillation with the remaining atria in sinus rhythm. In
      the maze III group, one patient was always on a regular rhythm, two had episodes
      of atrial fibrillation and one was in atrial fibrillation with controlled
      ventricular rate. Echocardiography showed atrial contraction in two maze I
      patients, but systolic atrial flow across both atrioventricular valves could only
      be demonstrated in two patients in the maze III group.

PMID- 9158133
TI  - Benefits of supplementing St Thomas' Hospital cardioplegic solution with
      tetraethylammonium on functional and metabolic recovery of isolated rat hearts.
AB  - This study was designed to evaluate whether the addition of potassium channel
      blockers, tetraethylammonium, 4-aminopyridine or glibenclamide, to St Thomas'
      cardioplegia improved myocardial preservation over that achieved by St Thomas'
      cardioplegic solution alone. Initially, isolated rat hearts were subjected to 30
      min of continuous normothermic hypoxic cardioplegia. Control hearts were arrested
      with St Thomas' cardioplegia followed by tetraethylammonium, glibenclamide or 4
      aminopyridine-enriched cardioplegia. Subsequently, in a second experiment, hearts
      were subjected to 45 min of normothermic global ischaemia, after 3 min of
      cardioplegia with either tetraethylammonium-enriched or standard St Thomas'
      cardioplegia. In both regimens, hearts arrested with tetraethylammonium-enriched
      St Thomas' cardioplegia showed better recovery of contractile function than
      controls (P<0.001). Creatine kinase levels were significantly lower in the
      tetraethylammonium group (P<0.001). 4-Aminopyridine treatment caused similar
      contractility to that of the control group but raised creatine kinase and lactate
      dehydrogenase levels (P<0.001). Glibenclamide diminished coronary flow
      autoregulation, and increased lactate dehydrogenase leakage in reperfusion
      (P<0.05) with similar contractility to controls. The results of this preliminary
      in vitro study demonstrate that, in rat heart, St Thomas' cardioplegia enriched
      with tetraethylammonium improves post-ischaemic contractile function and reduces
      creatine kinase release. It is concluded that high potassium blocks the membrane
      at the rapid depolarization phase with rapid sodium influx and tetraethylammonium
      further prevents repolarization by blocking voltage-dependent potassium channels.

PMID- 9158134
TI  - Artificial chordae in the treatment of anterior mitral leaflet pathology.
AB  - This report describes the authors' clinical experience with expanded
      polytetrafluorethylene (e-PTFE) sutures to replace the anterior mitral leaflet
      chordae for valve repair. Between November 1986 and July 1995, 203 patients
      underwent operations with e-PTFE chordae insertion. Among these, 122 had
      artificial chordae utilized for anterior mitral leaflet repair. Four patients had
      the valve replaced during the same operation because of an unsatisfactory result.
      One patient died from respiratory insufficiency 16 days after operation.
      Transoesophageal echocardiography at discharge from hospital showed no evidence
      of regurgitation in 81 cases, and trivial regurgitation in 36. During a mean
      follow-up of 36.6 (range 1-106) months two other patients died from causes
      unrelated to the valve repair, while one patient had a transient ischaemic attack
      returning to sinus rhythm. Two patients were reoperated on 12 and 18 months
      respectively after their initial operation for progression of valvular
      degeneration causing natural chordae rupture. Among the remaining 113 patients,
      111 are in New York Heart Association functional class I and yearly
      transoesophageal echocardiography has shown absent or trivial regurgitation. The
      utilization of e-PTFE as artificial chordae for anterior mitral leaflet pathology
      is a safe and reliable procedure, yielding excellent results and increasing the
      number of candidates for valve repair.

PMID- 9158135
TI  - Continuous transoesophageal echocardiography monitoring during weaning from
      cardiopulmonary bypass in children.
AB  - The purpose of this study was to evaluate the effectiveness of transoesophageal
      echocardiography monitoring during weaning from cardiopulmonary bypass after
      intracardiac repair in children. The left ventricular ejection fraction, left
      ventricular end-diastolic volume and left ventricle wall motion were monitored
      continuously by transoesophageal echocardiography in controls weaned easily from
      cardiopulmonary bypass (group A, n = 25), and those weaned with difficulty from
      cardiopulmonary bypass after mechanically assisted circulation (group B, n = 16).
      In group A, left ventricular ejection fraction and left ventricle wall motion
      were within normal range, and did not change significantly during weaning after
      cardiopulmonary bypass when compared with pre-bypass data. In contrast, left
      ventricular ejection fraction, left ventricular end-diastolic volume and left
      ventricle wall motion in group B during the first trial of weaning from bypass
      were significantly worsened. Hence, assisted circulation was performed until the
      data obtained via transoesophageal echocardiography improved with regard to
      maintenance of fluid balance, catecholamine dosage and assisted pump flow. All
      cases in group B were weaned safely from cardiopulmonary bypass despite their
      critical condition. In conclusion, continuous transoesophageal echocardiography
      monitoring may be a useful tool in children with severe heart failure for safe
      weaning from cardiopulmonary bypass after intracardiac repair.

PMID- 9158136
TI  - Kidney salvage in a case of ruptured renal artery aneurysm: case report and
      literature review.
AB  - A 79-year-old woman presented with hypovolaemic shock caused by rupture of a left
      renal artery aneurysm. She was successfully treated by arterial reconstruction
      with functional salvage of the kidney. The frequency of renal artery aneurysms,
      their risk of rupture and the results of urgent surgery are discussed.

PMID- 9158137
TI  - Characterisation of expression of mDMAHP, a homeodomain-encoding gene at the
      murine DM locus.
AB  - We examined the expression of the murine homologue of myotonic dystrophy
      associated homeodomain protein (mDMAHP) using two different strategies. The first
      approach, RT-PCR, detected spliced transcripts in a wide range of embryonic and
      adult tissues, in a pattern overlapping substantially with the expression of
      mDMPK. A second approach, the generation of transgenic mice expressing the lacZ
      reporter gene from a 4.3 kb promoter fragment, also demonstrated expression in a
      range of tissues with potential links to the phenotype in myotonic dystrophy. We
      conclude that murine DMAHP has a similar pattern of expression to human DMAHP and
      will serve as a useful model for functional studies of this gene, although
      species differences, such as the reduced CpG island (1.8 kb compared with 3.5 kb)
      must be carefully considered.

PMID- 9158139
TI  - Autosomal dominant cerulean cataract is associated with a chain termination
      mutation in the human beta-crystallin gene CRYBB2.
AB  - Congenital cataracts are a common major abnormality of the eye that frequently
      cause blindness in infants. At least a third of all cases are familial; autosomal
      dominant congenital cataract (ADCC) appears to be the most common familial form
      in the Western world. Cerulean cataracts have peripheral bluish and white
      opacifications in concentric layers with occasional central lesions arranged
      radially. Although the opacities may be observed during fetal development and
      childhood, usually visual acuity is only mildly reduced until adulthood, when
      lens extraction is generally necessary. We have been studying a family (ADCC-1)
      with cerulean blue ADCC, in which the affected daughter of a first cousin mating
      was presumed to be homozygous for the cataract gene. Recently, we mapped an ADCC
      gene in this family to a region of chromosome 22 containing three beta-crystallin
      genes. Here we report that a chain-termination mutation in CRYBB2 is associated
      with ADCC in this family.

PMID- 9158140
TI  - Homozygous alpha6 integrin mutation in junctional epidermolysis bullosa with
      congenital duodenal atresia.
AB  - Junctional epidermolysis bullosa with congenital pyloric or duodenal atresia is a
      distinct variant within this group of autosomal recessive blistering skin
      diseases. In this study we demonstrate, for the first time, a homozygous mutation
      in the alpha6 integrin gene (ITGA6) in a family with three affected individuals.
      For this purpose, we first determined the genomic organization of ITGA6, and
      placed the gene on chromosome 2q by high resolution radiation hybrid mapping.
      Heteroduplex analysis of PCR products containing the individual exons of ITGA6,
      followed by direct nucleotide sequencing, revealed that the proband was
      homozygous for a G-to-T transversion in the +1 position of intron 12. This
      mutation, 1856+1G-->T, affects an invariant base of the 5' donor splice site
      predicting aberrant splicing involving exon 12. The mutation was verified in the
      proband's DNA by restriction enzyme digestion which also confirmed that the
      parents were heterozygous carriers of this mutation. Altered expression of alpha6
      integrin, which forms a heterodimer with the beta4 subunit at the dermal
      epidermal junction, would explain fragility and blistering as a result of minor
      trauma to the skin.

PMID- 9158138
TI  - Apparent digenic inheritance of Waardenburg syndrome type 2 (WS2) and autosomal
      recessive ocular albinism (AROA).
AB  - Waardenburg syndrome (WS) is a clinically and genetically heterogeneous disease
      accounting for >2% of the congenitally deaf population. It is characterized by
      deafness in association with pigmentary anomalies and various defects of neural
      crest-derived tissues. At least four types are recognized (WS1, WS2, WS3 and WS4)
      on the basis of clinical and genetic criteria. Two previously described families
      seemed to delineate a new subtype characterized by WS2 in conjunction with ocular
      albinism (OA). Since mutations in the MITF gene are responsible for some
      instances of WS2, we screened for mutations in one of the WS2-OA families and
      discovered a 1 bp deletion in exon 8 of MITF. OA previously has been associated
      with compound heterozygosity for a mutant TYR allele and the TYR(R402Q) allele, a
      functionally significant polymorphism that is associated with moderately reduced
      tyrosinase catalytic activity. In this family, all of the individuals with the OA
      phenotype are either homozygous or heterozygous for TYR(R402Q), and heterozyous
      for the 1 bp deletion in MITF This suggests that the WS2-OA phenotype may result
      from digenic interaction between a gene for a transcription factor (MITF) and a
      gene that it regulates (TYR).

PMID- 9158141
TI  - Structure and sequence variation at the human leptin receptor gene in lean and
      obese Pima Indians.
AB  - The cloning of human and mouse cDNAs from brain that encode high affinity leptin
      receptors was recently reported. We have physically localized the human leptin
      receptor gene (LEPR) to a region at 1p31, between the anonymous microsatellite
      markers D1S515 and D1S198. The genomic structure of the human leptin receptor
      gene, corresponding to the published human brain cDNA sequence, spans over 70 kb
      and includes 20 exons. Since the leptin receptor gene is a candidate gene for
      obesity, and because of its proximity to D1S198, a marker previously linked to
      insulin secretion, the LEPR gene was sequenced in 20 non-diabetic Pima Indians
      chosen for extremes in percent body fat and in their acute insulin response to
      intravenous glucose. Seven polymorphic sites were identified. Two of these
      polymorphisms, Lys109Arg and Gln223Arg, are amino acid substitutions in the
      extracellular domain of the leptin receptor, one polymorphism is a silent
      substitution, and four occur in non-coding regions of the leptin receptor. Four
      of these sites are in linkage disequilibrium with one another. Nucleotides at
      three noncoding polymorphic sites were found exclusively in obese Pima Indians.
      This demonstrates an association between variation at the leptin receptor gene
      and obesity in humans.

PMID- 9158142
TI  - Mutations causing achondroplasia and thanatophoric dysplasia alter bFGF-induced
      calcium signals in human diploid fibroblasts.
AB  - Mutations in the fibroblast growth factor receptor (FGFR) gene family recently
      have been shown to underlie several hereditary disorders of bone development,
      with specific FGFR3 mutations causing achondroplasia (Ach) and thanatophoric
      dysplasia (TD). However, for none of these mutations has the defect in receptor
      function been demonstrated directly and, therefore, for none has the
      pathophysiological mechanism of the disease been defined. Using our established
      techniques for single-cell ratiometric real-time calcium image analysis, we
      defined the nature of the basic fibroblast growth factor (bFGF)-induced calcium
      signal in human diploid fibroblasts, and, in blinded studies, have analyzed the
      bFGF-induced signals from 18 independent fibroblast cell lines, including
      multiple lines from patients with known mutant alleles of FGFR3 and syndromes of
      Ach or TD. Control cells responded with transient increases in intracellular
      calcium, with many cells showing oscillatory calcium waves. Homozygous Ach cell
      lines failed to signal, whereas heterozygous Ach lines responded nearly normally.
      We observed heterogeneous signals in TD heterozygotes: the unresponsive lines all
      turned out to carry TD1 alleles, whereas all responsive lines had TD2 alleles.
      Since FGFR1, 2 and 3 receptors are known to be expressed in fibroblasts, our
      results suggest that specific mutant FGFR3 alleles can function in a dosage
      dependent dominant-negative fashion to inactivate FGFR signaling.

PMID- 9158143
TI  - Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling.
AB  - Achromatopsia is an autosomal recessive disease of the retina, characterized
      clinically by an inability to distinguish colors, impaired visual acuity,
      nystagmus and photophobia. A genome-wide search for linkage was performed using
      an inbred Jewish kindred from Iran. To facilitate the genome-wide search, we
      utilized a DNA pooling strategy which takes advantage of the likelihood that the
      disease in this inbred kindred is inherited by all affected individuals from a
      common founder. Equal molar amounts of DNA from all affected individuals were
      pooled and used as the PCR template for short tandem repeat polymorphic markers
      (STRPs). Pooled DNA from unaffected members of the kindred was used as a control.
      A reduction in the number of alleles in the affected versus control pool was
      observed at several loci. Upon genotyping of individual family members,
      significant linkage was established between the disease phenotype and markers
      localized on chromosome 2. The highest LOD score observed was 5.4 (theta = 0).
      When four additional small unrelated families were genotyped, the combined peak
      LOD score was 8.2. Analysis of recombinant chromosomes revealed that the disease
      gene lies within a 30 cM interval which spans the centromere. Additional fine
      mapping studies identified a region of homozygosity in all affected individuals,
      narrowing the region to 14 cM. A candidate gene for achromatopsia was excluded
      from this disease interval by radiation hybrid mapping. Linkage of achromatopsia
      to chromosome 2 is an essential first step in the identification of the disease
      causing gene.

PMID- 9158145
TI  - Molecular and clinical correlations in spinocerebellar ataxia 2: a study of 32
      families.
AB  - Spinocerebellar ataxia 2 (SCA2) is caused by the expansion of an unstable CAG
      repeat encoding a polyglutamine tract. One hundred and eighty four index patients
      with autosomal dominant cerebellar ataxia type I were screened for this mutation.
      We found expansion in 109 patients from 30 families of different geographical
      origins (15%) and in two isolated cases with no known family histories (2%). The
      SCA2 chromosomes contained from 34 to 57 repeats and consisted of a pure stretch
      of CAG, whereas all tested normal chromosomes (14-31 repeats), except one with 14
      repeats, were interrupted by 1-3 repeats of CAA. As in other diseases caused by
      unstable mutations, a strong negative correlation was observed between the age at
      onset and the size of the CAG repeat (r = -0.81). The frequency of several
      clinical signs such as myoclonus, dystonia and myokymia increased with the number
      of CAG repeats whereas the frequency of others was related to disease duration.
      The CAG repeat was highly unstable during transmission with variations ranging
      from -8 to +12, and a mean increase of +2.2, but there was no significant
      difference according to the parental sex. This instability was confirmed by the
      high degree of gonadal mosaicism observed in sperm DNA of one patient.

PMID- 9158144
TI  - The molecular basis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in
      compound heterozygous patients: is there correlation between genotype and
      phenotype?
AB  - Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most commonly
      recognized defect of mitochondrial beta-oxidation. It is potentially fatal, but
      shows a wide clinical spectrum. The aim of the present study was to investigate
      whether any correlation exists between MCAD genotype and disease phenotype. We
      determined the prevalence of the 14 known and seven previously unknown non-G985
      mutations in 52 families with MCAD deficiency not caused by homozygosity for the
      prevalent G985 mutation. This showed that none of the non-G985 mutations are
      prevalent, and led to the identification of both disease-causing mutations in 14
      families in whom both mutations had not previously been reported. We then
      evaluated the severity of the mutations identified in these 14 families. Using
      expression of mutant MCAD in Escherichia coli with or without co-overexpression
      of the molecular chaperonins GroESL we showed that five of the missense mutations
      affect the folding and/or stability of the protein, and that the residual enzyme
      activity of some of them could be modulated to a different extent depending on
      the amounts of available chaperonins. Thus, some of the missense mutations may
      result in relatively high levels of residual enzyme activity, whereas the
      mutations leading to premature stop codons will result in no residual enzyme
      activity. By correlating the observed types of mutations identified to the
      clinical/biochemical data in the 14 patients in whom we identified both disease
      causing mutations, we show that a genotype/phenotype correlation in MCAD
      deficiency is not straightforward. Different mutations may contribute with
      different susceptibilities for disease precipitation, when the patient is
      subjected to metabolic stress, but other genetic and environmental factors may
      play an equally important role.

PMID- 9158146
TI  - alpha-Mannosidosis: functional cloning of the lysosomal alpha-mannosidase cDNA
      and identification of a mutation in two affected siblings.
AB  - a-Mannosidosis (MIM 248500) is an autosomal recessive lysosomal storage disorder
      resulting from deficient activity of lysosomal alpha-mannosidase (LAMAN) (EC
      3.2.1.24). The disease is characterized by massive intracellular accumulation of
      mannose-rich oligosaccharides with resulting mental retardation, hearing loss,
      immune deficiency and skeletal changes. We report here the purification and
      characterization of human placenta LAMAN. The enzyme is synthesized as a single
      chain precursor which is processed into three glycopeptides of 70, 42 and 15 kDa.
      The 70 kDa peptide is further partially proteolysed into three more peptides that
      are joined by disulfide bridges. The laman cDNA sequence was assembled from
      overlapping fragments obtained by PCR on human fibroblast and human lung cDNA.
      The deduced amino acid sequence contains a putative signal peptide of 48 amino
      acids followed by a polypeptide sequence of 962 amino acids. Northern blot
      analyses revealed a single transcript of approximately 3.5 kb present in all
      tissues examined but at varying levels. Two affected siblings of Palestinian
      origin were homozygous for a mutation that causes a His-->Leu replacement at a
      position which is conserved among class 2 alpha-mannosidases from several
      species.

PMID- 9158147
TI  - Sequence analysis, identification of evolutionary conserved motifs and expression
      analysis of murine tcof1 provide further evidence for a potential function for
      the gene and its human homologue, TCOF1.
AB  - The gene mutated in Treacher Collins syndrome, an autosomal dominant disorder of
      facial development, has recently been cloned. While the function of the predicted
      protein, Treacle, is unknown, it has been shown to share a number of features
      with the highly phosphorylated nucleolar phosphoproteins, which play a role in
      nucleolar-cytoplasmic transport. In the current study, the murine homologue of
      the Treacher Collins syndrome gene has been isolated and shown to encode a low
      complexity, serine/alanine-rich protein of 133 kDa. Interspecies comparison
      indicates that the proteins display 61.5% identity, with the level of
      conservation being greatest in the regions of acidic/basic amino acid repeats and
      nuclear localization signals. These features are shared with the nucleolar
      phosphoproteins. Confirmation that the gene isolated in the current study is
      orthologous with the Treacher Collins syndrome gene was provided by the
      demonstration that it mapped to central mouse chromosome 18 in a conserved
      syntenic region with human chromosome 5q21-q33. Expression analysis in the mouse
      indicated that the gene was expressed in a wide variety of embryonic and adult
      tissues. Peak levels of expression in the developing embryo were observed at the
      edges of the neural folds immediately prior to fusion, and also in the developing
      branchial arches at the times of critical morphogenetic events. These
      observations support a role for the gene in the development of the craniofacial
      complex and provide further evidence that the gene encodes a protein which may be
      involved in nucleolar-cytoplasmic transport.

PMID- 9158148
TI  - Profound biotinidase deficiency caused by a point mutation that creates a
      downstream cryptic 3' splice acceptor site within an exon of the human
      biotinidase gene.
AB  - Biotinidase recycles the vitamin biotin from biocytin upon the degradation of the
      biotin-dependent carboxylases. We have identified a novel point mutation within
      the biotinidase gene that encodes the signal peptide in two unrelated individuals
      with profound biotinidase deficiency. Sequence analysis of genomic DNA from these
      individuals revealed a G to A transition (G100-->A) located 57 bases downstream
      of the authentic splice acceptor site in exon B. Although this mutation predicts
      a G34S substitution, it also generates a 3' splice acceptor site. Sequence of the
      PCR-amplified cDNA from the homozygous child revealed that all the product was
      shorter than that of normal individuals and was the result of aberrant splicing.
      The aberrantly spliced transcript lacked 57 bases, including a second in-frame
      ATG, that encode most of the putative signal peptide and results in an in-frame
      deletion of 19 amino acids. The mutation results in failure to secrete the
      aberrant protein into the blood. This is the first reported example in which a
      point mutation creates a cryptic 3' splice acceptor site motif that is used
      preferentially over the upstream authentic splice site. The preferential usage of
      the downstream splice site is not consistent with the 5'-3' scanning model, but
      is consistent with the exon definition model of RNA splicing.

PMID- 9158149
TI  - Mild congenital muscular dystrophy in two patients with an internally deleted
      laminin alpha2-chain.
AB  - Congenital muscular dystrophy (CMD) is a group of clinically and genetically
      heterogeneous disorders inherited in an autosomal recessive mode. The alpha2
      chain of laminin-2 (previously called merosin) has been shown by
      immunohistochemical and genetic analyses to be implicated in the pathogenesis of
      the 'classic' form of CMD. In the 'merosin-deficient' subgroup, which represents
      about half of the cases, more definite evidence of the involvement of the laminin
      alpha2-chain has recently been reported with the identification of mutations in
      the gene encoding the alpha2-chain of laminin 2 (LAMA2) in CMD patients. Here we
      report on two siblings from a consanguineous family expressing an internally
      deleted laminin alpha2-chain as a result of a splice site mutation in the LAMA2
      gene which causes the splicing of exon 25. The predicted protein lacks 63 amino
      acids in domain IVa which forms a globular structure on the short arm of the
      alpha2-chain. Interestingly, these patients appear mildly affected compared to
      others who completely lack this protein. This situation presents a striking
      analogy with Becker muscular dystrophy, where in-frame deletions in the
      dystrophin gene result in the expression of a semi-functional protein and lead to
      a mild phenotype.

PMID- 9158150
TI  - Congenital myasthenic syndromes due to heteroallelic nonsense/missense mutations
      in the acetylcholine receptor epsilon subunit gene: identification and functional
      characterization of six new mutations.
AB  - We describe and functionally characterize six mutations of the acetylcholine
      receptor (AChR) epsilon subunit gene in three congenital myasthenic syndrome
      patients. Endplate studies demonstrated severe endplate AChR deficiency,
      dispersed endplate regions and well preserved junctional folds in all three
      patients. Electrophysiologic studies were consistent with expression of the fetal
      gamma-AChR at the endplates in one patient, prolongation of some channel events
      in another and gamma-AChR expression as well as some shorter than normal channel
      events in still another. Genetic analysis revealed two recessive and
      heteroallelic epsilon subunit gene mutations in each patient. One mutation in
      each (epsilonC190T [epsilon R64X], epsilon 127ins5 and epsilon 553del 7)
      generates a nonsense codon that predicts truncation of the epsilon subunit in its
      N-terminal, extracellular domain; and one mutation in each generates a missense
      codon (epsilon R147L, epsilon P245L and epsilon R311W). None of the mutations was
      detected in 100 controls. Expression studies in HEK cells indicate that the three
      nonsense mutations are null mutations and that surface expression of AChRs
      harboring the missense mutations is significantly reduced. Kinetic analysis of
      AChRs harboring the missense mutations show that epsilon R147L is kinetically
      benign, epsilon P245L prolongs burst open duration 2-fold by slowing the rate of
      channel closing and epsilon R311W shortens burst duration 2-fold by slowing the
      rate of channel opening and speeding the rate of ACh dissociation. The modest
      changes in activation kinetics are probably overshadowed by reduced expression of
      the missense mutations. The consequences of the endplate AChR deficiency are
      mitigated by persistent expression of gamma-AChR, changes in the release of
      transmitter quanta and appearance of multiple endplate regions on the muscle
      fiber.

PMID- 9158151
TI  - Mutations in different functional domains of the human muscle acetylcholine
      receptor alpha subunit in patients with the slow-channel congenital myasthenic
      syndrome.
AB  - Congenital myasthenic syndromes are a group of rare genetic disorders that
      compromise neuromuscular transmission. A subset of these disorders, the slow
      channel congenital myasthenic syndrome (SCCMS), is dominantly inherited and has
      been shown to involve mutations within the muscle acetylcholine receptor (AChR).
      We have identified three new SCCMS mutations and a further familial case of the
      alpha G153S mutation. Single channel recordings from wild-type and mutant human
      AChR expressed in Xenopus oocytes demonstrate that each mutation prolongs channel
      activation episodes. The novel mutations alpha V156M, alpha T254I and alpha S269I
      are in different functional domains of the AChR alpha subunit. Whereas alpha
      T254I is in the pore-lining region, like five of six previously reported SCCMS
      mutations, alpha S269I and alpha V156M are in extracellular domains. alpha S269I
      lies within the short extracellular sequence between M2 and M3, and identifies a
      new region of muscle AChR involved in ACh binding/channel gating. alpha V156M,
      although located close to alpha G153S which has been shown to increase ACh
      binding affinity, appears to alter channel function through a different molecular
      mechanism. Our results demonstrate heterogeneity in the SCCMS, indicate new
      regions of the AChR involved in ACh binding/channel gating and highlight the
      potential role of mutations outside the pore-lining regions in altering channel
      function in other ion channel disorders.

PMID- 9158152
TI  - Reduced penetrance of the Huntington's disease mutation.
AB  - Controversy persists concerning the significance of Huntington disease (HD)
      alleles in the 36-39 repeat range. Although some clinically affected persons have
      been documented with repeats in this range, elderly unaffected individuals have
      also been reported. We examined 10 paternal transmissions of HD alleles of 37-39
      repeats in collateral branches of families with de novo HD. All 10 descendants,
      including many who are elderly, are without symptoms of HD. Forty percent of the
      transmissions were unstable, although none varied by more than one repeat. The
      observation that individuals with alleles of 37-39 repeats may survive unaffected
      beyond common life expectancy supports the presence of reduced penetrance for HD
      among some persons with repeat sizes which overlap the clinical range. Non
      penetrance may be increased in the collateral branches of de novo mutation
      families when compared to penetrance estimates from patient series. There was no
      CAA-->CAG mutation for the penultimate glutamine in either a de novo expanded 42
      repeat allele or the corresponding non-penetrant 38 repeat allele in a family
      with fresh mutation to HD.

PMID- 9158153
TI  - Human PEG1/MEST, an imprinted gene on chromosome 7.
AB  - The mouse Peg1/Mest gene is an imprinted gene that is expressed particularly in
      mesodermal tissues in early embryonic stages. It was the most abundant imprinted
      gene among eight paternally expressed genes (Peg 1-8) isolated by a subtraction
      hybridization method from a mouse embryonal cDNA library. It has been mapped to
      proximal mouse chromosome 6, maternal duplication of which causes early embryonic
      lethality. The human chromosomal region that shares syntenic homology with this
      is 7q21-qter, and human maternal uniparental disomy 7 (UPD 7) causes apparent
      growth deficiency and slight morphological abnormalities. Therefore, at least one
      paternally expressed imprinted gene seems to be present in this region. In this
      report, we demonstrate that human PEG1/MEST is an imprinted gene expressed from a
      paternal allele and located on chromosome 7q31-34, near D7S649. It is the first
      imprinted gene mapped to human chromosome 7 and a candidate for a gene
      responsible for primordial growth retardation including Silver-Russell syndrome
      (SRS).

PMID- 9158154
TI  - Molecular defects in Sanfilippo syndrome type A.
AB  - Sanfilippo A syndrome (mucopolysaccharidosis type IIIA, MPS-IIIA) is an autosomal
      recessive neurodegenerative disorder due to an enzymatic defect of the lysosomal
      enzyme sulphamidase (EC 3.10.1.1) required for the degradation of heparan
      sulphate. In this study, molecular defects in the sulphamidase gene of MPS-IIIA
      patients were investigated in a group of 10 patients of Australian and American
      origin. The entire coding region of the sulphamidase gene was RT-PCR amplified
      and one polymorphism (R456H), four novel mutations (S66W, R245H, E447K, 1307 del
      9) and one previously described mutation (1284 del 11) were identified by direct
      PCR sequencing. R245H was present in six patients including one severely affected
      homozygote. In three of the other patients with R245H, second mutant alleles were
      identified as S66W, 1284 del 11 and E447K, respectively. S66W was also detected
      in another patient where the other mutant allele remains undefined. In addition,
      1307 del 9 was also detected in a patient with the other mutant allele remaining
      undefined. Allele specific oligonucleotide hybridisation was used to determine
      the incidence of these in a population of 26 MPS-IIIA patients (Australian and
      American) and 60 normal controls (Australian). R245H represented 27% (14/52
      alleles) in this total patient population, while the other three changes ranged
      from 1.9 to 9.6% (1-5 of 52 alleles). The sequence variant, R456H, was shown to
      be polymorphic as it was present in 55% of normal and 38% of patient alleles. The
      total combined incidence of these five is 46% of alleles. This is the first study
      of the molecular defects in MPS-IIIA patients and will greatly assist the
      development of molecular analysis for MPS-IIIA patients and studies concerned
      with genotype to phenotype relationships.

PMID- 9158156
TI  - Estimating Y chromosome specific microsatellite mutation frequencies using deep
      rooting pedigrees.
AB  - Recently, a set of highly polymorphic chromosome Y specific microsatellites
      became available for forensic, population genetic and evolutionary studies.
      However, the lack of a mutation frequency estimate for these loci prevents a
      reliable application. We therefore used seven chromosome Y tetranucleotide repeat
      loci to screen 42 males who are descendants from 12 'founding fathers' by a total
      number of 213 generations. As a result, we were able to estimate an average
      chromosome Y tetranucleotide mutation frequency of 0.20% (95% CIL 0.05-0.55).
      This closely matches the often cited Weber and Wong estimate of 0.21% for a set
      of autosomal tetranucleotide repeats. Expanding the set of microsatellites with
      two more loci (a tri- and a penta-nucleotide repeat locus) an average chromosome
      Y microsatellite mutation frequency of 0.21% (95% CIL 0.06-0.49) was found. These
      estimates suggest that microsatellites on the Y chromosome have mutation
      frequencies comparable to those on the autosomes. This supports the hypothesis
      that slippage-generated growth is the driving force behind the microsatellite
      variability.

PMID- 9158155
TI  - Mouse pale ear (ep) is homologous to human Hermansky-Pudlak syndrome and contains
      a rare 'AT-AC' intron.
AB  - Hermansky-Pudlak syndrome (HPS) is a rare, often fatal, autosomal recessive
      disorder in which albinism, bleeding and lysosomal storage are associated with
      defects of diverse cytoplasmic organelles, including melanosomes, platelet dense
      granules and lysosomes. Similar multi-organellar defects occur in the Chediak
      Higashi syndrome (CHS), as well as in a large number of different mouse mutants.
      The HPS gene is located in 10q23, and two genetically distinct mouse loci, pale
      ear (ep) and ruby-eye (ru), both with mutant phenotypes similar to human HPS, map
      close together in the homologous region of murine chromosome 19, suggesting that
      one of these loci might be homologous to human HPS. We recently identified the
      human HPS gene, which encodes a novel ubiquitously-expressed transmembrane
      protein of unknown function. Here, we describe characterization of the mouse Hps
      cDNA and genomic locus, and identification of pathologic Hps gene mutations in ep
      but not in ru mice, establishing mouse pale ear as an animal model for human HPS.
      The phenotype of homozygous ep mutant mice encompasses those of both HPS and CHS,
      suggesting that these disorders may be closely related. In addition, the mouse
      and human HPS genes both contain a rare 'AT-AC' intron, and comparison of the
      sequences of this intron in the mouse and human genes identified conserved
      sequences that suggest a possible role for pre-mRNA secondary structure in
      excision of this rare class of introns.

PMID- 9158157
TI  - Identification of functionally important regions of the muscular chloride channel
      CIC-1 by analysis of recessive and dominant myotonic mutations.
AB  - Mutations in the muscular voltage-dependent Cl-channel, CIC-1, lead to recessive
      and dominant myotonia. Here we analyse the effects of one dominant (G200R) and
      three recessive (Y150C, Y261C, and M485V) mutations after functional expression
      in Xenopus oocytes. Glycine 200 is a highly conserved amino acid located in a
      conserved stretch in the putatively cytoplasmic loop between domains D2 and D3.
      Similar to several other dominant mutations the amino acid exchange G200R leads
      to a drastic shift by approximately 65 mV of the open probability curve to more
      positive voltages. As explored by co-expression studies, the shift is
      intermediate in heteromeric mutant/WT channels. Open channel properties such as
      single channel conductance, rectification or ion selectivity are not changed.
      Thus we identified a new region of the CIC-1 protein in which mutations can lead
      to drastic shifts of the voltage dependence. The recessive mutation M485V, which
      is located in a conserved region at the beginning of domain D10, leads to a
      drastic reduction of the single channel conductance from 1.5 pS for WT to
      approximately 0.3 pS. In addition, the mutant is strongly inwardly rectifying and
      deactivates incompletely at negative voltages. Ion-selectivity, however, is
      unchanged. These electrophysiological properties fully explain the recessive
      phenotype of the mutation and identify a new region of the protein that is
      involved in ion permeation and gating of the CIC-1 channel. The other two
      recessive mutations (Y150C and Y261C) had been found in a compound heterozygous
      patient. Surprisingly, expression of these mutants in oocytes yielded currents
      indistinguishable from WT CIC-1 when explored by two-electrode voltage clamp
      recording and patch clamping (either singly or both mutations co-expressed).
      Other mechanisms that are not faithfully represented by the Xenopus expression
      system must therefore be responsible for the myotonic symptoms associated with
      these mutations.

PMID- 9158158
TI  - Identification of a major susceptibility locus on chromosome 6p and evidence for
      further disease loci revealed by a two stage genome-wide search in psoriasis.
AB  - Psoriasis is a common chronic inflammatory disorder of the skin. To further
      understand the pathogenesis of psoriasis we have chosen to investigate the
      molecular genetic basis of the disorder. We have used a two-stage approach to
      search the human genome for the location of genes conferring susceptibility to
      psoriasis, using a total of 106 affected sibling pairs identified from 68
      independent families. As over a third of the extended kindreds included affected
      relatives besides siblings, in addition to an analysis of allele sharing between
      affected sibling pairs, a novel linkage strategy was applied that extracts full
      non-parametric information. Four principal regions of possible linkage were
      identified on chromosomes 2, 8, 20 (p <0.005) and markers from the MHC region at
      6p21 (p <0.0000006) for which significant evidence of linkage disequilibrium was
      also observed (p <0.00002). Whilst data from limited case control associations
      exist to implicate the MHC, the results of this genome wide analysis demonstrate
      that, at least in the population studied, a gene or genes located within the MHC
      and close to the class 1 HLA loci, represent the major determinant of the genetic
      basis of psoriasis.

PMID- 9158159
TI  - Missense mutations in exon 6 of the survival motor neuron gene in patients with
      spinal muscular atrophy (SMA).
AB  - Spinal muscular atrophy (SMA) is a frequent autosomal recessive neurodegenerative
      disorder leading to weakness and atrophy of voluntary muscles. The survival motor
      neuron gene (SMN) is a strong candidate for SMA and present in two highly
      homologous copies (telSMN and cenSMN) within the SMA region (5q11.2-q13.3). More
      than 90% of SMA patients show homozygous deletions of at least exon 7 of telSMN,
      whereas absence of cenSMN seems to have no clinical consequences. In 23 non
      deleted SMA patients, we searched for intragenic mutations of the SMN genes in
      exons 1-7 and the promotor region by single strand conformation analysis. We
      identified two different missense mutations, S2621 and T2741, in exon 6 of telSMN
      in three independent SMA families, providing further evidence for the telSMN gene
      as a SMA determining gene. Both mutations, as well as two previously described
      mutations (Y272C and G279V) are located within a highly conserved interval from
      codon 258 to codon 279 which seems to be an important functional domain of the
      telSMN protein. Recently, this region has been shown to contain a
      tyrosine/glycine-rich motif, which is also present in various RNA binding
      proteins, suggesting a potential role of SMN in RNA metabolism. Missense
      mutations might be useful for in vivo and transgenic experiments and further
      investigations on understanding the function of the telSMN protein.

PMID- 9158160
TI  - The mottled mouse as a model for human Menkes disease: identification of
      mutations in the Atp7a gene.

PMID- 9158161
TI  - Atrio-ventricular valve dysplasia in 22 newborn infants.
AB  - We retrospectively studied the experience of our institution with isolated
      dysplasia of one or both atrio-ventricular valves in 22 newborn infants. All
      patients with associated cardiac malformations were excluded. Ten patients
      exhibited isolated tricuspid valve dysplasia. One patient had tricuspid valve
      dysplasia and a dysplastic pulmonary valve. In 10 patients, both atrio
      ventricular valves were affected. Finally, mitral valve dysplasia was associated
      with pulmonary valve stenosis in 1 case. Associated syndromes and/or chromosomal
      anomalies were: Down syndrome (n=2), trisomy 18 (n=1), Noonan syndrome (n=1),
      Marfan syndrome (n=3), Ehlers-Danlos and Cutis laxa (n=2). Mortality was 27.2%
      during follow-up (mean 51 months): 3 patients with chromosomal aneuploidies, 2
      patients with severe neonatal Marfan syndrome and 1 with Ehlers-Danlos.
      Complications were: sustained supra-ventricular tachycardia in 3, neonatal
      staphylococcal tricuspid valve endocarditis in 1, persistent significant valvular
      disease in 8. In the remaining 9 survivors, the dysplasia of the atrio
      ventricular valves persists with absent or mild incompetence. Beside obvious
      chromosomal anomalies, newborn infants with dysplastic valves should be
      investigated for manifestations of connective tissue disorders. This may help to
      identify new pleiotropic syndromes which include valvular dysplasia as one
      manifestation.

PMID- 9158162
TI  - Coronary microcirculation evaluation with transesophageal echocardiography
      Doppler in type II diabetics.
AB  - Evaluation of coronary microvascular function can be obtained through coronary
      flow reserve measurements. The aim of this study was to evaluate the coronary
      microvascular function by using transesophageal-Doppler echocardiographic
      assessment of coronary flow reserve. The study included 32 normotensive patients
      with type II diabetes mellitus (group A) of short duration (6.1+/-3.8 years) aged
      55.4+/-9.4 years and 14 healthy volunteers matched for age, gender and BMI (group
      B). No patients had clinical evidence of coronary artery disease and all of them
      produced a negative recent stress ECG test. Excluded from the study were patients
      with anemia, left ventricular hypertrophy, arrhythmia, congenital, or acquired
      structural heart disease. All subjects underwent transesophageal-Doppler
      echocardiography. Satisfactory coronary blood flow velocity recordings could be
      obtained from the initial segment of the left anterior descending coronary artery
      in healthy volunteers and in 27 patients at baseline and 2 min after dipyridamole
      infusion (0.56 mg/kg, for 4 min). In the remaining 5 patients no satisfactory
      recordings were available. The indexes of coronary flow reserve, i.e. the ratios
      of dipyridamole over basal maximum and mean diastolic velocities were calculated.
      Dipyridamole/rest maximal coronary reserve (Table 3) was 1.946+/-0.743, while
      this ratio for the mean diastolic velocity was 1.969+/-0.805 in group A. The
      respective values for group B, were 2.811+/-0.345 (P=0.000 vs. group A) and
      2.914+/-0.303 (P=0.000 vs. group A). Thus, the increase in coronary flow reserve
      although present in both groups, it was more impressive in the normal group.
      Multiple regression logistic analysis of: age, sex, smoking, glucosylated
      hemoglobin, duration of diabetes and type of therapy, did not show any
      correlation of these parameters with the above ratios. This study shows that
      coronary flow reserve, as measured with transesophageal echocardiography-Doppler,
      is severely impaired in normotensive patients with type II diabetes, with
      relatively short duration of the disease.

PMID- 9158163
TI  - Expression rate of vinculin isoforms in human aortocoronary saphenous vein
      grafts.
AB  - Aortocoronary bypass conduits derived from saphenous veins usually develop
      diffuse intimal thickening, one of the major causes of haemodynamically relevant
      graft stenosis. To elucidate the role of smooth muscle cell proliferation in late
      graft failure, specimens from highly stenotic or occluded vein grafts implanted
      into the arterial circulation for more than 5 years were tested for their
      expression rate of meta-vinculin. Since the cytoskeletal protein meta-vinculin is
      present exclusively in contractile smooth muscle cells, the determination of the
      relative amounts of meta-vinculin (150 kDa) and its low-molecular weight isoform
      vinculin (130 kDa) allows characterization of the phenotypic status of smooth
      muscle cells. Using immunoblotting techniques, the quantitative relation of meta
      vinculin in tissue samples obtained from autoptic vein grafts (n=10) was measured
      and compared with those of native saphenous veins (n=6). In vein grafts, the
      fractional meta-vinculin content of the total vinculin immunoreactivity ranged
      from 32%-46% (mean 39.6%), whereas the range was 39%-53% (mean 46.7%) in native
      veins. By applying Student's t-test, a statistical significance was not
      demonstrated suggesting that the majority of smooth muscle cells in intimal
      thickenings consisted of a contractile phenotype. Immunohistochemically, the
      vinculin immunoreactivity in the intimal layer of vein grafts was reduced as
      compared to native saphenous veins. The distribution of vinculin in grafted veins
      closely resembled that in arteriosclerotic coronary arteries with intimal
      thickening. Hence, our biochemical data demonstrate parallels between the
      pathogenesis of late vein graft stenosis and degenerative arteriosclerotic
      lesions.

PMID- 9158164
TI  - Serum basic fibroblast growth factor levels in patients with ischemic heart
      disease.
AB  - BACKGROUND: Being a potent promoter of endothelial and smooth muscle cell
      proliferation, basic fibroblast growth factor (bFGF) is presumed to play a key
      role in coronary collateral development and atherogenesis. PURPOSE: To
      characterize serum bFGF levels in patients with ischemic heart disease. METHODS:
      The study population consisted of patients with angina (n=33) and after
      uncomplicated myocardial infarction (n=12). The number of significantly stenosed
      (> or = 50%) vessels and angiographic coronary collateral score were noted. Blood
      was drawn immediately prior to elective coronary angiography in study patients
      for bFGF levels. Twenty healthy, age-matched subjects served as control for serum
      bFGF. RESULTS: Serum bFGF levels were undetectable in all 20 control subjects,
      but were detectable in 15/33 (45%) patients with angina and 3/12 (25%) post
      infarction patients, respectively (P=0.002). Serum bFGF levels were detectable in
      13/23 (57%) patients with 0- or 1-vessel disease, as compared with 5/22 (23%)
      patients with 2- or 3-vessel disease (P<0.05). Detectable serum bFGF levels were
      not in correlation with coronary collateral score (P=1). CONCLUSIONS: Serum
      levels of bFGF are elevated in patients with ischemic heart disease, particularly
      in those with minimal coronary artery disease. We postulate that detectable serum
      bFGF levels reflect active atherogenesis rather than myocardial collateral
      development.

PMID- 9158165
TI  - Sympathetic inhibition with clonidine improves autonomic balance in congestive
      heart failure.
AB  - In this double-blind, placebo-controlled crossover study, we examined the effect
      of transdermal clonidine (given for 5 days) on autonomic control in 14 patients
      with mild to moderate congestive heart failure by heart rate variability
      analysis. Compared with placebo, clonidine increased the 24-h mean R-R interval
      from 718+/-110 to 811+/-117 ms (P<0.01), increased the S.D. of all normal RR
      intervals (SDNN) from 60.8+/-18.5 to 80.9+/-21.4 ms (P<0.01), the S.D. of the
      average RR intervals for all 5-min segments (SDANN) from 54.7+/-15.2 to 70.5+/
      18.4 ms (P<0.01) and the mean of the S.D.s of all RR intervals for all 5-min
      segments (SDNN index) from 29.2+/-8.3 to 36.5+/-8.1 ms (P<0.01). The root mean
      square successive differences (r-MSSD) and the percent of differences between
      adjacent RR intervals >50 ms (pNN50) were also increased from 18.3+/-6.7 to
      23.1+/-7.0 ms (P<0.01) and from 2.1+/-1.9 to 4.5+/-3.0% (P<0.01). In addition,
      total power, low frequency power and high frequency power were increased from
      641+/-322 to 898+/-403 ms2/Hz (P<0.01), from 149+/-97 to 216+/-133 ms2/Hz
      (P<0.01) and from 52.8+/-27.1 to 93.2+/-41.3 ms2/Hz (P<0.01), respectively. The
      plasma norepinephrine level was decreased significantly from 0.52+/-0.18 to
      0.24+/-0.09 ng/ml (P<0.01) after clonidine therapy. Changes in heart rate
      variability measures after clonidine administration were positively related to
      changes in plasma norepinephrine level. These results indicate that suppressing
      the sympathetic nervous system by clonidine improves autonomic balance in
      patients with congestive heart failure. But whether such restoration of the
      autonomic control has a beneficial effect on the long-term management of these
      patients still needs further investigation.

PMID- 9158166
TI  - Relationship between isokinetic muscle strength and exercise capacity in chronic
      heart failure.
AB  - The exercise intolerance and excessive ventilatory response to exercise of
      chronic heart failure is associated with abnormalities of skeletal muscle
      function, in particular a reduction in muscle strength. Isometric and isokinetic
      leg muscle strength were measured in 10 patients with chronic heart failure and
      10 age-matched controls. Each subject undertook maximal exercise testing to
      measure peak oxygen consumption (V(O2)) and the ventilatory response to exercise
      as measured by the slope of the relation between ventilation and carbon dioxide
      production (V(E)/V(CO2) slope). Quadriceps strength (mean (S.D.)) was reduced in
      heart failure as measured by isometric (444.9 (129.6) N vs. 556.0 (136.0);
      P<0.01) and isokinetic (123.6 (30.2) Nm vs. 146.8 (40.0); P=0.04). Hamstring
      strength was also reduced as measured by isokinetic testing (53.6 (15.6) Nm vs.
      71.1 (28.1); P=0.02). Isokinetic and isometric strengths correlated, but not
      closely (r=0.52, P<0.001). There were negative correlations between the
      V(E)/V(CO2) slope, and isokinetic measures: with average torque, r=-0.62,
      P<0.004; with peak torque, r=-0.64, P=0.002. We have found evidence for reduced
      muscle function affecting both knee flexors and extensors. This reduction in
      muscle strength correlates with the ventilatory response to exercise. These
      observations lend support to the muscle hypothesis of the generation of symptoms
      in chronic heart failure.

PMID- 9158167
TI  - Dependence of peak oxygen uptake on oxygen transport capacity in chronic heart
      failure: comparison of graded protocol and fixed protocol.
AB  - Oxygen transport capacity is the most important determinant of maximum oxygen
      uptake (V(O2) max) in healthy subjects, however, its role is controversial in
      patients with chronic heart failure (CHF). The aim of this study was to clarify
      whether the oxygen transport capacity is an actual determinant of exercise
      capacity in CHF patients. Thirteen CHF patients underwent two maximum exercise
      tests, i.e., a graded protocol test and a fixed protocol test, measuring
      expiratory gases, leg blood flow (LBF), and arterial and venous blood gases. The
      workload of the fixed protocol was set to exceed the peak workload obtained by
      the graded protocol. Exercise with the fixed protocol caused significantly larger
      peak V(O2) compared to the graded protocol (813+/-194 to 971+/-203 ml/min,
      P<0.001). Peak LBF increased by 17%, while the peak leg arterio-venous oxygen
      difference increased by 5% from the graded protocol to the fixed protocol. The
      linear correlation between leg venous partial oxygen pressure and peak V(O2) was
      more clearly manifested in the fixed protocol (r=0.60, P<0.05) than in the graded
      protocol (r=0.47, NS). In conclusion, the exercise with graded protocol did not
      always conduct the upper limit of oxygen demand/supply relationship in CHF
      patients, whereas, the fixed protocol with a larger workload produced larger peak
      V(O2) and manifested the mechanism to limit V(O2) by oxygen transport capacity.

PMID- 9158168
TI  - Cardiac arrhythmias as presenting symptoms in patients with limb-girdle muscular
      dystrophy.
AB  - Clinically manifest muscular dystrophy is often accompanied by functional and
      anatomic derangements in the myocardium which often have prognostic significance.
      We describe two young patients who had unrecognized limb-girdle muscular
      dystrophy who presented with cardiac arrhythmia. One developed dilated
      cardiomyopathy complicated by ventricular tachyarrhythmia. The other patient had
      atrial paralysis requiring permanent pacing. It is important to consider the
      possibility of underlying muscular dystrophy in patients who present with cardiac
      arrhythmia without an obvious cause.

PMID- 9158169
TI  - Predictors of quality of life after hospital admission for heart attack or
      angina.
AB  - This study tests the hypothesis that it is possible to predict people who will
      have a low quality of life (QOL) 6 months after hospital admission for acute
      myocardial infarction (AMI) or angina. Among 424 patients discharged from
      hospital in the Hunter Region of New South Wales with a diagnosis of AMI or
      angina, follow-up questionnaires were received from 303 at 6 months. Baseline
      data collected during hospitalisation included demographic variables and the
      'emotional' factor of a disease-specific QOL measure using a modified and
      validated self-administered questionnaire. The full QOL measure comprises
      'emotional', 'physical' and 'social' factors, each factor being assessed at the 6
      month follow-up. Only baseline 'emotional' QOL score and sex predicted 6-month
      QOL scores in patients with AMI. Scores were consistently lower in patients with
      angina, in whom marital and employment status, having had a previous AMI, current
      cigarette smoking, the presence of cardiac failure and baseline emotional QOL
      were all significantly associated with the 6-month QOL scores. The assessment of
      simple measures during hospitalisation for angina can be helpful in predicting
      those who will have a low QOL 6 months later. They may represent a high-risk
      group at whom counselling could be directed.

PMID- 9158170
TI  - Dynamic 3-D-echo in the preoperative assessment of left atrial myxoma in a 51
      year-old male.

PMID- 9158171
TI  - Abolition of Torsade de Pointes after radiofrequency catheter ablation at right
      ventricular outflow tract.
AB  - Radiofrequency (RF) catheter ablation was tried to treat a patient with syncope,
      perhaps due to polymorphic ventricular tachycardia (VT) of Torsade de Pointes
      (TdP) type which was documented by Holter monitoring. Electrophysiological study
      showed that the isolated ventricular extrasystoles (VEs) that initiated TdP were
      exactly replicated by pace mapping at the septal site of the right ventricular
      outflow tract. Performance of RF ablation at this site abolished the TdP and
      episodes of syncope with no requirement for antiarrhythmic agents for 3 years,
      whereas isolated VEs persisted. Although it is difficult to mention whether RF
      ablation was successful or not in this case, this procedure should be considered
      as a potentially curative approach to the TdP, when the arrhythmogenic focus can
      be fixed and identified as in this case.

PMID- 9158172
TI  - Lipid abnormalities in Greek patients with coronary artery disease.
AB  - Lipid abnormalities are major risk factors for premature coronary artery disease
      (CAD). However, the type and prevalence of dyslipidemia in these patients have
      not been well characterised, especially in some ethnic groups. The purpose of the
      present work was to determine the lipid disorders in patients of Northwestern
      Greece with premature CAD. The study population comprised of 132 men and 38 women
      who underwent elective diagnostic arteriography in our University Hospital.
      Subjects with > or = 1 lesion that narrowed the lumen of any of the 15 coronary
      artery segments by > or = 70% were considered to be CAD cases (n=108), whereas
      those with narrowing < 70% were excluded (n=54). Asymptomatic subjects (n=104)
      matched for age and sex were taken as controls. Compared with the controls,
      patients with premature CAD had increased serum levels of total cholesterol, LDL
      cholesterol, triglycerides, Apo B, and Lp(a), and decreased serum levels of HDL
      cholesterol and Apo A1. A lipoprotein or apolipoprotein abnormality was
      identified in 89 CAD patients (82.4%). The increased serum Apo B level (> 130
      mg/dl) was the most common lipid abnormality observed in 72 patients. However,
      the most prevalent dyslipidemic phenotypes in our patients were type IIA followed
      by hypoalpha and hyperApoB. Compared to the control population, CAD patients had
      increased incidence of IIA and hypoalpha phenotypes. On the contrary, a normal
      lipoprotein phenotype was more common in the control population compared to CAD
      patients (56.7% vs. 17.6%, P<0.001). We conclude that the majority of Greek
      patients with premature CAD exhibit lipid and lipoprotein abnormalities, which to
      a large extent can be defined by determining the traditional lipid parameters
      (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides). However,
      in some cases the value of the quantification of other lipid parameters such as
      apolipoproteins and Lp(a) should be taken into account.

PMID- 9158174
TI  - Role of infarction artery status in left ventricular remodeling after acute
      myocardial infarction.
AB  - The aim of this study was to evaluate the relation between the infarction artery
      status and left ventricular volumes, independently of regional ventricular
      dysfunction, at 4-6 weeks after a first myocardial infarction. The study group
      consisted of 100 patients, of whom 80 received thrombolytic treatment. Coronary
      and contrast left ventricular angiograms were performed at 36+/-5 days
      postinfarction. Left ventricular end-diastolic and end-systolic volumes were
      measured. The centerline chord motion method was used to calculate the extent of
      wall motion abnormality (percentage of chords with hypokinetic motion) and its
      severity (maximum units of S.D. below the normal wall motion reference). Minimum
      lumen diameter, patency and collateral flow in the infarction artery were also
      analyzed. Eight patients (group I) showed occlusion with poor collateral flow in
      the infarction artery, 22 patients (group II) occlusion with good collateral
      flow, 38 patients (group III) severe residual stenosis (minimum lumen diameter <
      or = 1 mm), and 32 patients (group IV) non-severe residual stenosis (minimum
      lumen diameter > 1 mm). Patients from group I presented greater wall motion
      abnormality in terms of both extent (P=0.005) and severity (P=0.007), and greater
      end-diastolic (P=0.07) and end-systolic (P=0.0008) volumes; there were no
      differences among groups II, III and IV. By stepwise multivariate regression
      analysis, the extent of wall motion abnormality was the main determinant of end
      diastolic (P=0.0001) and end-systolic (P=0.0001) volumes; occlusion with poor
      collateral flow was also a significant independent factor for end-systolic volume
      (P=0.03). Total occlusion (including both with and without collaterals) and the
      minimum lumen diameter did not correlate with end-diastolic and end-systolic
      volumes. We concluded that (A) the extent of regional dysfunction is the primary
      determinant of left ventricular volumes at 4-6 weeks postinfarction. (B) The
      status of the infarction artery is a weak predictor of end-diastolic volume,
      which is the best descriptor of ventricular remodeling, although occlusion with
      poor collateral flow is associated to larger end-systolic volume.

PMID- 9158173
TI  - Salt intake and blood pressure in Nigerian hypertensive patients.
AB  - Discretionary salt intake (habitual) of male and female Nigerian hypertensive
      patients presenting in hospital was assessed and this was correlated with their
      blood pressure. Their salt intake was assessed by questionnaires and direct
      interview following detailed explanation. They were categorised into low,
      moderate and high salt intake groups according to a standard criterion. The 114
      hypertensive patients (52 males; 62 females) were aged 26-80 years (mean 52.2+/
      1.8 (S.E.M.) males; 53.7+/-1.7 females, P=0.5). Those on medication were
      generally poorly compliant with uncontrolled blood pressure at presentation.
      Fifty percent belonged to the moderate salt intake group. No female reported high
      salt intake. In the males, the mean DBP in the high salt intake group was
      significantly higher than in the moderate and low intake groups (123.5+/-4.4,
      108.3+/-3.9 and 99.3+/-7.7 mmHg; P<0.02 and P<0.009, respectively). There was no
      significant difference between the mean DBP of the low and moderate salt intake
      groups (P>0.1). The SBP is also consistently higher from the low to the high salt
      intake groups (162.1+/-15.5, 179.3+/-7.4 and 180.8+/-7.6 mmHg, respectively),
      although the difference is not statistically significant (P>0.1). The BMI did not
      differ between the salt groups (P>0.5) and there was no correlation between BMI
      and blood pressure (P>0.05). The study suggests that the higher the salt intake,
      the higher the blood pressure, particularly the diastolic, in male hypertensive
      patients. The picture in the female is unclear, since none reported a high salt
      intake. Reduced salt intake might, therefore, be beneficial in black hypertensive
      patients, in the setting of common presentation at the stage of cardiac
      decompensation.

PMID- 9158175
TI  - Unusual presentation of an atrial septal aneurysm with left atrial myxoma: a case
      report.
AB  - A 68-year-old man with coronary artery disease and mitral regurgitation was
      referred for surgery. Intraoperative transoesophageal echocardiogram revealed
      mild mitral regurgitation, and an aneurysm of the atrial septum deviating to the
      right atrial side with mass in the left atrium. During operation the aneurysm of
      the atrial septum was excised with a small sessile myxoma from base of the atrial
      septum (2.5 cm X 2 cm X 1.5 cm).

PMID- 9158176
TI  - Concurrent balloon dilatation of mitral and tricuspid stenosis during pregnancy
      using an Inoue balloon.
AB  - Percutaneous balloon dilatation of combined mitral and tricuspid stenoses was
      performed successfully in a 22-year-old woman during the 23rd week of pregnancy,
      using an Inoue balloon catheter. Following valvuloplasty, mean transmitral
      gradients decreased from 36 to 5 mmHg and the mean transtricuspid gradients from
      12 to 3 mmHg. The procedure was uncomplicated and well tolerated, leading to the
      vaginal delivery of a healthy newborn at term. The fluoroscopy time required was
      84 s for mitral and 18 s for tricuspid valvuloplasty. The present report
      highlights the advantage of the Inoue balloon catheter for multivalvular
      dilatation during pregnancy with minimum fluoroscopy time.

PMID- 9158177
TI  - Angiographical and computed tomographic findings in diffuse pulmonary
      arteriovenous fistulas.
AB  - We reported two rare cases of diffuse pulmonary arteriovenous fistulas in infants
      and children. Both pulmonary angiography and chest computed tomography were
      obtained and revealed fine network formations clearly, from which the final
      diagnosis was made.

PMID- 9158178
TI  - Transbrachial coil occlusion of the first intercostal branch of an internal
      mammary artery bypass graft for angina.
AB  - Percutaneous transbrachial insertion of a metallic coil into the first
      intercostal branch of the left internal mammary artery resulted in resolution of
      severe angina in a 60-year-old man who had coronary artery bypass surgery 14
      years previously. The diagnosis of coronary artery steal was made clinically.
      This case illustrates the importance of recognising coronary steal in patients
      who redevelop angina after coronary artery surgery with the use of an
      incompletely prepared left internal mammary artery as a conduit. The diagnosis
      can be made clinically and the condition treated without the need for further
      surgery.

PMID- 9158179
TI  - Neoplastic angina: a case report.
AB  - A 54-year-old Caucasian woman, with a 1-year history of exertional angina was
      investigated by means of coronary angiography. On injection of contrast into both
      coronary arteries an unusual area of capillary blushing was seen around the point
      of a left main stem stenosis. At surgery a mass was seen arising from the area of
      the aortic root extending around the left main stem. Histology confirmed this to
      be an aortic paraganglioma. Three-vessel coronary artery bypass grafting was
      performed and at 6-month follow-up the patient remained symptom free.

PMID- 9158180
TI  - Severe right ventricular dysfunction following pericardiocentesis for cardiac
      tamponade.
AB  - The accumulation of fluid in the pericardium in an amount sufficient to cause
      severe obstruction to blood inflow to the ventricles results in cardiac
      tamponade. In this condition, relief of intrapericardial pressure by
      pericardiocentesis usually dramatically improves cardiac output, and can be
      lifesaving. We report a case of a patient with malignant cardiac tamponade in
      which cardiogenic shock developed after pericardiocentesis due to severe right
      ventricular dysfunction.

PMID- 9158181
TI  - Coronary artery bypass grafting in a patient with total occlusion of both
      internal carotid arteries.

PMID- 9158182
TI  - Principles and guidelines for surgeons--management of symptomatic breast cancer.
      European Society of Surgical Oncology.
AB  - The European Society of Surgical Oncology is actively involved in the promotion
      of a high standard of surgical oncology throughout Europe. Such an ambition
      involves recognition of Centres of Excellence in the management of cancer
      patients throughout Europe. These centres have a multi-disciplinary system
      involved in the total care of patients with cancer and are concerned with the
      delivery of care to the highest available standards. It is accepted that not all
      patients with cancer can, nor should, necessarily be treated in such highly
      specialized centres. Yet all cancer patients should be guaranteed a high standard
      of care. High surgical standards can be ensured if surgeons treating cancer are
      trained in specialist centres and, when in independent practice, follow
      established guidelines or protocols of treatment. In common with many national
      surgical oncology societies, the European Society of Surgical Oncology is in the
      process of establishing good practice guidelines in the treatment of solid
      tumours. This document on the management of symptomatic breast cancer is the
      first of a series of guidelines to be proposed by ESSO. It draws heavily on
      excellent documents already in existence from the British Association of Surgical
      Oncology and from the Danish Breast Cancer Co-Operative Group. It is hoped that
      this document will be sufficiently clear and purposeful to be of help to the
      individual surgeon and yet sufficiently flexible to allow it to be adopted in the
      different medical systems throughout Europe.

PMID- 9158183
TI  - Treatment in germ cell tumours: state of the art.
AB  - Although the majority of patients with disseminated germ cell tumours can be
      cured with cisplatin-based chemotherapy, mortality is still up to 20%. Several
      prognostic factors have been identified to differentiate between patients with a
      good, intermediate or poor prognosis. In this review we discuss the recent
      chemotherapy trials, which were designed to reduce toxicity in good-prognosis
      patients and to improve efficacy in intermediate- and poor-prognosis patients. In
      good-prognosis patients it is obvious that the omission of bleomycin and the
      replacement of cisplatin by carboplatin has no place in first-line standard
      treatment. The reduction of four standard courses of bleomycin, etoposide and
      cisplatin (BEP) to three is shown possible in one study, but a confirmatory study
      is currently ongoing in the EORTC. In intermediate- and poor-prognosis patients,
      the use of new agents or alternating regimens (with or without shortened
      intervals) did, by now, not improve final outcome. The role of high-dose
      chemotherapy remains to be determined. Against this background, four courses of
      standard-dose BEP should still be considered treatment of first choice in the
      majority of patients with disseminated germ cell tumours. Furthermore, the policy
      in clinical stage I disease has been reviewed. In clinical stage I seminoma
      patients the policy is to apply adjuvant radiotherapy, while the strategy in
      patients with non-seminomatous tumours (surveillance, retroperitoneal lymph node
      dissection or adjuvant chemotherapy in high-risk patients) depends highly on the
      local situation, such as the operating skills of the urologist, and on the
      possibilities for tight follow-up. Of patients with true resistance for up-front
      BEP chemotherapy 90% will normally die. In patients who achieve a complete
      response on first-line chemotherapy, but relapse thereafter 30% will have no
      evidence of disease with second-line chemotherapy (VIP). In this group of
      patients results with high-dose chemotherapy seem promising, but its value should
      preferentially be determined in either a randomized fashion or by long-term
      follow-up from a large group of patients according to a similar protocol. The use
      of post-chemotherapy surgery is an essential part of management for metastatic
      non-seminomatous germ cell tumours, while the majority of residual masses in pure
      seminoma will disappear spontaneously, and frequent follow-up is recommended
      instead of surgical intervention.

PMID- 9158184
TI  - Future trials in germ cell malignancy (GCM) of the testis.
AB  - With overall cure in excess of 95%, there is a debate about how to conduct
      further trials. Three areas are reviewed: (1) Relapse and high risk patients.
      With a plethora of new drugs and high dose salvaging one in three second-line
      failures, there is plenty of choice. Substituting taxol for etoposide in
      etoposide, ifosfamide and cisplatin (VIP), followed by high dose, is one
      possibility. (2) For low-risk metastatic disease the current priority is to
      recruit large numbers to the EORTC/MRC three vs four courses bleomycin, etoposide
      and cisplatin (BEP) and 3 vs 5 day etoposide trial to evaluate the safety of
      risking less toxic treatment. (3) For stage 1 disease, non-seminoma, quality of
      life assessments and evaluating patient participation in decisions about adjuvant
      therapy are the principal priorities. For seminoma one course carboplatin, the
      first realistic alternative to radiotherapy, is currently being tested in a MRC
      trial. During the next decade there will be two areas of interest in addition to
      those above. Firstly, trials of testis conservation to reduce the use of
      orchidectomy on diagnosis. For advanced drug-resistant disease, gene therapy
      using candidate genes found to be responsible for a chemotherapy response, and
      exploration of their role within non-germ cell cancer.

PMID- 9158185
TI  - Factors affecting surgical margin clearance in screen-detected breast cancer and
      the effect of cavity biopsies on residual disease.
AB  - One hundred and fourteen localization biopsies for screen-detected breast cancers
      were assessed for surgical margin clearance and presence of tumour in the cavity
      biopsies or subsequent resections. Inadequate surgical clearance (< or = 1 mm
      from the margin) in 88 patients was associated with high nuclear grade ductal
      carcinoma in situ, or extensive in-situ change accompanying invasive carcinomas,
      vs pure invasive carcinomas. Smaller localization biopsies (< or =50 g), larger
      tumours, and absence of a definite fine-needle aspiration cytological diagnosis
      of malignancy were also associated with inadequate excision. The radiographic
      characteristics of the tumours did not correlate with inadequate excision. Sixty
      five patients had cavity biopsies taken at the time of surgery and 23 (35%)
      biopsies were positive, 20 of which were associated with incompletely excised
      tumours. Further excision in 78 patients yielded residual disease in 63%, most of
      whom had had inadequate surgical clearance. When cavity biopsies were taken with
      incompletely excised tumours, 15 of 88 subsequent resection specimens harboured
      residual disease compared with 29 of 88 without cavity biopsies. Although cavity
      biopsies increase the clearance margin, a negative cavity biopsy is not always an
      assurance of adequate excision.

PMID- 9158186
TI  - Wire-directed localization biopsy of the breast: an audit of results and analysis
      of factors influencing therapeutic value in the treatment of breast cancer.
AB  - Fine-wire localization biopsy is an accurate technique for diagnosis of
      mammographically-detected breast abnormalities, and may also be therapeutic in
      the management of impalpable malignant lesions. A number of factors were
      therefore examined regarding their influence upon therapeutic success in a
      consecutive series of 129 localization biopsies. Factors included type of
      radiological abnormality, method and accuracy of wire localization and pre
      operative cytology. Primary malignancy was detected at initial localization in 64
      cases (malignant:benign ratio, 1.11:1); 26 (41%) achieving adequate local tumour
      excision margins without further surgery, and 38 undergoing further surgery to
      clear margins (mastectomy in 23, further wide excision in 15). Therapeutic
      success was related to the accuracy of pre-operative needle localization (needle
      hook within 1 cm of target lesion in 26/26 (100%) therapeutic biopsies, compared
      to 29/38 (76%) non-therapeutic biopsies (P<0.01, Fisher's exact test)); and to
      pre-operative cytology (suspicious/malignant cytology in 15/24 therapeutic,
      compared with only 9/29 non-therapeutic biopsies (P=0.013, chi-squared)).
      Localization biopsy has a high diagnostic success rate and a therapeutic value
      dependent upon accurate pre-operative cytological diagnosis, supplemented by
      precise needle localization of the target lesion.

PMID- 9158187
TI  - Changing attitudes towards breast-conserving treatment of early breast cancer in
      the south-eastern Netherlands: results of a survey among surgeons and a registry
      based analysis of patterns of care.
AB  - To see whether personal preferences of surgeons can explain the trends in the use
      of breast-conserving therapy (BCT) of early breast cancer, questionnaires were
      sent to the surgeons of seven community hospitals in the south-eastern
      Netherlands in 1987 and 1995. The answers were set against the actual use of
      breast-conserving therapy in the hospitals in the period 1984-94, as monitored by
      the Eindhoven Cancer Registry. The proportion of surgeons who were willing to use
      BCT for tumours < or =3 cm increased from 43% in 1987 to 93% in 1995. In 1995,
      the majority of the surgeons considered multicentric tumour growth, diffuse
      microcalcifications on the mammogram and an extensive intraductal component
      around the tumour as contraindications for breast-conserving therapy. The
      proportion of patients with an operable, non-metastasized breast tumour of < or
      =5 cm in diameter undergoing breast-conservative surgery increased from 31% in
      1984 to 60% in 1989 (P<0.01) and remained at that level in 1990 and 1991. Between
      1991 and 1993, the proportion receiving breast-conservative surgery decreased
      significantly for patients younger than 50 years and a tumour 2.1-3.0cm in
      diameter, and also for those 50-69 years old with a tumour < or =2.0cm or 3.1
      5.0cm across. The observed decrease in BCT in the south-eastern Netherlands in
      some subgroups seems to reflect the growing awareness of potential risk factors
      for local recurrence following BCT.

PMID- 9158188
TI  - Tumor size and axillary metastasis, a correlative occurrence in 1244 cases of
      breast cancer between 1980 and 1995.
AB  - A review of 1244 breast cancer cases from the Tumor Registry of Northwest
      Community Hospital between 1980 and 1995 was carried out to investigate the
      incidence of axillary metastasis. There were 442 patients (35.45%) with positive
      nodes. The small lesions were graded to ascertain if size and grade of small
      tumors can be used to predict axillary metastasis. One hundred and seventy-nine
      cases of < or = 1.0 cm were retrospectively reviewed by one pathologist. Tumors
      <0.4 cm had negative nodes. Those with nuclear and histologic grades of 1 had 3%
      positive nodes, the remainder had positive nodes ranging from 11% to 19%.
      Infiltrating duct cancers of nuclear grade 3, histologic grade 2, and positive
      nodes, showed a 40% mortality. Eighteen patients died in the 0.5-1.0 cm tumor
      size range, mostly of histologic grade 2 and nuclear grade 3. Nuclear and
      histologic grade 1 tumors with infiltrating duct cancers had negative nodes and
      showed a good prognosis. Based on this study, node dissection can be omitted in
      these patients and in those with tumors < or = 0.4 cm. For all other lesions,
      full axillary node dissection and detailed pathologic examination is still the
      gold standard for evaluating the axilla.

PMID- 9158189
TI  - Technetium-99m-sestamibi uptake in axillary lymph node metastases in breast
      cancer patients.
AB  - In a prospective study the value of technetium-99m-sestamibi scintigraphy (MIBI
      scintigraphy) in staging axillary lymph node involvement in breast cancer
      patients was established. The study comprised 36 cases. The results of the
      staging were compared with physical and histological examination. MIBI
      scintigraphy had a sensitivity of 91% and a total accuracy of 81%. These
      percentages demonstrate the potential value of this technique; larger series will
      be needed to confirm our results.

PMID- 9158190
TI  - Medical care utilization by incurable cancer patients in a Swedish county.
AB  - A retrospective study of patients with cancer diagnoses treated at a Swedish
      county hospital was carried out in order to analyse medical care utilization by
      incurable cancer patients. All 208 patients customarily treated at the Department
      of General Surgery in Ostersund Hospital for cancer diagnoses during 1 year were
      included in the study. The main outcome measures were: number of institutional
      days; admissions; duration of terminal hospitalization. The Department of General
      Surgery supplied 7570 of all 12,276 (62%) institutional days needed throughout
      the disease course. The terminal hospitalization (i.e. the period of continuous
      institutional care ending with the death of the patient) constituted 39% of all
      institutional days. The duration of the terminal hospitalization seemed to be
      unrelated to various diagnoses and demographic variables. Patients with cancer of
      the breast utilized most institutional days/patient (median 80 institutional
      days) during the disease course. Married patients and patients living within a 40
      km radius of the hospital spent significantly more days at the Department of
      General Surgery during the last 6 months of life than did the unmarried and those
      living further afield.

PMID- 9158191
TI  - Tumour marker CA 50 levels compared to signs and symptoms in the diagnosis of
      pancreatic cancer.
AB  - The diagnostic merits of CA 50 and of symptoms indicating pancreatic cancer
      (pain, jaundice, weight loss, malabsorption) were compared prospectively in 512
      consecutive patients. Among the final diagnoses were: exocrine pancreatic cancer,
      175; periampullary cancer, 44; other gastrointestinal cancer, 45; and chronic
      pancreatitis, 64 cases. The suspected diagnoses based on symptoms and signs were
      correct in 80% of the patients with exocrine pancreatic cancer, in 78% with
      periampullary, in 76% with other gastrointestinal cancer and in 90% with chronic
      pancreatitis. CA 50 was pathological in 96% of the cases with exocrine pancreatic
      cancer, in 70% with periampullary, in 78% with other gastrointestinal
      malignancies and in 36% with chronic pancreatitis. The sensitivity was 96%,
      specificity 48%, positive prediction 49% and negative prediction 96%, depending
      on cut-off level. The single CA 50 value was comparable to symptoms and signs
      regarding sensitivity and negative prediction. In 28 of 42 cases incorrectly
      clinically classified, CA 50 alone indicated a benign or malignant diagnosis. If
      both the modalities 'signs and symptoms' and CA 50 were combined, the sensitivity
      was 91%, the specificity 92%, the positive prediction 86% and the negative
      prediction 95%. The initial CA 50 value can help to indicate in which patients a
      pancreatic malignancy should be suspected.

PMID- 9158193
TI  - David Patey's contributions to surgical oncology.

PMID- 9158192
TI  - Adenocarcinoma of bladder.
AB  - Forty-eight patients with adenocarcinoma (21 urachal and 27 non-urachal) of the
      bladder were treated at the Tata Memorial Hospital between 1976 and 1992. The
      study group consisted of 32 men and 16 women. The urachal tumours were more
      common in younger patients (mean age: 49 years) than were non-urachal tumours
      (mean age: 58 years). The overall 5-year survival in this series was 37%. Stage
      and grade were powerful predictors of outcome. Patients with non-urachal tumours
      showed an overall survival rate of 29.9% compared with 45.7% in patients with
      urachal tumours (P= 0.14). Radical cystectomy was the most common treatment
      modality in patients with non-urachal tumours and yielded an overall 5-year
      survival of 35%. Patients with urachal tumours were treated with either partial
      cystectomy or radical cystectomy. The 5-year survival following partial
      cystectomy was 56.3% compared with 25.9% following a radical cystectomy and the
      difference between the two was not statistically significant (P = 0.76).

PMID- 9158194
TI  - Steroid hormones and cancer: (III) observations from human subjects.
AB  - Epidemiological evidence strongly suggests that steroid hormones are implicated
      in the risk of cancers of the breast, ovary and endometrium. However, it has
      proved difficult to implicate specific hormones or show that measurement of
      circulating hormones can identify women who will go on to develop malignant
      disease. There are, however, more convincing data that a proportion of
      established cancers are dependent upon steroid hormones for their continued
      growth and these underpin the use of endocrine manoeuvres in the treatment of
      these malignancies. Increased knowledge of the synthesis, release and mechanism
      of action of steroid hormones has led to the development of novel therapies for
      endocrine sensitive cancer and on-going research can reasonably be expected to
      identify tumour markers which can accurately predict hormone-dependency and
      provide better understanding of the mechanism by which response and resistance to
      therapy occur. The hope is that this knowledge will translate into more effective
      and rational endocrine treatment benefiting increased numbers of patients.

PMID- 9158195
TI  - Surgical management of patients with advanced cancer (I).

PMID- 9158197
TI  - Villous adenoma of the distal appendix.
AB  - Villous adenoma confined to the distal appendix has not been previously reported
      in conjunction with acute apendicitis. The presence of an adenoma indicates a
      need for further investigation due to an association with neoplasia elsewhere.

PMID- 9158198
TI  - Umbilical port metastasis from gallbladder carcinoma after laparoscopic
      cholecystectomy.
AB  - A case of gallbladder carcinoma is presented where metastatic tumour developed at
      the abdominal wall port site following laparoscopic cholecystectomy.

PMID- 9158199
TI  - Porta choledochal fistula: an unusual complication of a cholangiocarcinoma
      arising from a type I choledochal cyst.
AB  - A vena porta choledochal fistula caused by an adenocarcinoma arising from a type
      I choledochal cyst was detected in a 42-year-old woman. The diagnostic and
      therapeutic aspects of this malignancy are discussed.

PMID- 9158200
TI  - Chest wall resection and reconstruction for metastatic basal cell carcinoma.

PMID- 9158201
TI  - The need for surgeons to participate in Clinical Trials.

PMID- 9158202
TI  - Pharmacology of immunosuppressive medications used in renal diseases and
      transplantation.
AB  - As understanding of the molecular basis for the immune response has expanded
      rapidly, so have the possibilities for designing therapeutic interventions that
      are more effective, more specific, and safer than current treatment options. The
      promise of therapeutic advances in the future is based on the rapidly expanding
      insights into the pathogenesis of abnormal immunologic reactions. Nowhere is the
      understanding of molecular mechanisms, pathophysiology, and targeted therapy more
      relevant than in the field of renal transplantation, which makes up much of the
      clinical database for the use of immunosuppressive therapy for renal disease.
      Despite the recent advances in basic immunology, clinical validation of new
      agents and approaches is lacking for most drugs at present. This review will
      focus in the pharmacology of agents used in the therapy of immunologic renal
      disease and in renal transplantation. It should be recognized that clinical
      pharmacology and experience with newer agents is limited, and potential utility
      is based largely on experimental data.

PMID- 9158203
TI  - Familial glomerulopathy with giant fibrillar (fibronectin-positive) deposits: 15
      year follow-up in a large kindred.
AB  - A 15-year clinical follow-up is reported for a familial glomerulopathy
      characterized on light microscopy by the glomerular deposition of giant
      fibrillary deposits (Virchows Arch A Pathol Anat Histol 388:313-326, 1980). On
      electron microscopy, the deposits consist of randomly oriented fibrils (12 to 16
      nm in width and 120 to 170 nm in length). These deposits show positive
      immunoreactivity for fibronectin. One hundred fifty-seven of 197 family members
      within five generations were investigated. The disease is characterized by the
      occurrence of albuminuria in the third to fourth decades of life and slow
      progression to end-stage renal disease over a period of 15 to 20 years with the
      occurrence of generalized distal tubular acidosis (renal tubular acidosis type
      IV), hypertension, and the nephrotic syndrome. The frequent occurrence of
      otherwise unexplained microalbuminuria in young individuals of generations IV and
      V could be indicative of incipient glomerular disease. In one affected male
      individual and in his unaffected sister, renal cell carcinoma was diagnosed,
      raising the possibility that this familial glomerulopathy might be associated
      with an increased risk to develop renal cell cancer by direct or indirect
      (associated genetic predisposition) mechanisms. The disease relapsed in one renal
      transplant, raising the possibility of the presence of a transferable factor that
      could be part of the deposited fibrillar material or, alternatively, interfere
      with the glomerular handling of the deposited material.

PMID- 9158204
TI  - Fibrillary glomerulonephritis related to serum fibrillar immunoglobulin
      fibronectin complexes.
AB  - Fibrillary glomerulonephritis is a disease of uncertain origin and pathogenesis
      characterized by nonamyloidotic fibrils in glomeruli. We report
      immunohistological, immunochemical, and biochemical studies of a serum fibrillar
      cryoprecipitate obtained from a patient with fibrillary glomerulonephritis, that
      formed on prolonged storage at 4 degrees C. By Western blot and amino acid
      sequence analysis, the cryoprecipitated fibril components consisted of
      immunoglobulins, heavy chains gamma and mu, light chains kappa and lambda, and
      fibronectin, similar to the proteins identified by immunofluorescence and
      immunoelectron microscopy in the glomerular fibrils. These findings support the
      hypothesis that serum precursors may be the source of the fibrillar deposits and
      suggest a role for immunoglobulin-fibronectin complexes in the pathogenesis of
      fibrillary glomerulonephritis.

PMID- 9158205
TI  - Intercellular adhesion molecule-1, intercellular adhesion molecule-3, and
      leukocyte integrins in leukocyte accumulation in membranoproliferative
      glomerulonephritis type I.
AB  - Marked intraglomerular infiltration of leukocytes is observed in
      membranoproliferative glomerulonephritis (MPGN). We recently demonstrated that
      this leukocyte infiltration develops partly through macrophage-1 (Mac-1)-positive
      cells and glomerular C3c deposits (Clin Exp Immunol 100:269-276, 1995). To
      further investigate the mediation of adhesion molecules in the leukocyte
      accumulation, we immunohistochemically examined the expression of intraglomerular
      leukocyte integrins and their ligands as well as surface markers for
      granulocytes/monocytes (CD15) and macrophages (CD68) in 26 patients with MPGN
      type I who had undergone repeated biopsies. These patients were divided into two
      groups. Group A included the patients who showed both normo-complementemia and
      urinary protein excretion less than 1 g/d at the follow-up biopsy (recovery
      group: n = 14). Group B (persistent group: n = 12) included the patients other
      than those in group A. At the initial biopsy, there was no difference in the
      degree of glomerular C3c deposition, glomerular intercellular adhesion molecule
      (ICAM)-1 expression, or the numbers of cells bearing leukocyte function
      associated antigen-1 (LFA-1), Mac-1, and ICAM-3 between the two groups. At the
      follow-up biopsy, the degree of glomerular C3c deposition, and the numbers of
      cells bearing LFA-1, Mac-1, and ICAM-3, were significantly decreased only in
      group A (P < 0.01, P < 0.001, P < 0.001, and P < 0.01, respectively). No
      chronological change in ICAM-1 expression was observed in either group. Group B
      showed a chronological increase in the severity of glomerular injury and serum
      creatinine level, associated with persistent heavy proteinuria. Neither LFA-1-
      nor Mac-1-positive cells were positively correlated with ICAM-1 expression. Most
      of Mac-1-positive cells were CD15-positive cells (granulocytes/monocytes), and a
      considerable number of Mac-1-positive cells concurrently expressed ICAM-3. In
      contrast, most LFA-1-positive cells were considered to be CD68-positive cells
      (macrophages). The number of cells bearing LFA-1 was positively correlated with
      that of cells bearing ICAM-3 (P < 0.00001). These results suggest that the
      glomerular leukocytes, infiltrating through Mac-1/complement interaction, express
      ICAM-3 by themselves, and that LFA-1/ICAM-3 interaction might participate in the
      glomerular aggregation of leukocytes in MPGN type I. In this study, we could not
      conclude that LFA-1/ICAM-1 or Mac-1/ICAM-1 interaction was involved in the
      leukocyte accumulation in this disease.

PMID- 9158206
TI  - Extracapillary glomerulonephritis and renal amyloidosis.
AB  - We report three patients with well-documented renal amyloidosis who developed
      rapidly progressive renal failure. Renal biopsies from all three patients showed
      crescentic glomerulonephritis imposed on renal amyloidosis. All patients were
      treated with intravenous high-dose methylprednisolone pulses combined with
      immunosuppressive agents and oral corticosteroids. Partial recovery of renal
      function was obtained in two patients. For the third patient, treatment had to be
      stopped after a few days because of a septic arthritis. Renal function continued
      to deteriorate, and the patient had to be placed on regular hemodialysis. We
      conclude that extracapillary glomerulonephritis may occasionally complicate a
      preexisting renal amyloidosis and may be reversible if recognized early and
      treated appropriately.

PMID- 9158207
TI  - The magnitude of metabolic acidosis is dependent on differences in bicarbonate
      assays.
AB  - Metabolic acidosis has been recently recognized as an important comorbid event in
      the high mortality rates seen in patients with end-stage renal disease. The
      recognition of hypobicarbonatemia is dependent on a reliable assay for total
      carbon dioxide (TCO2). It is common practice for dialysis facilities to send
      blood samples for testing to remote laboratories, which may assay bicarbonate
      differently than the local hospital. We noted that serum bicarbonate
      concentrations from blood samples sent to our reference laboratory were
      significantly lower (4 mEq/L) compared with blood samples sent to our local
      laboratory. Blood samples were assayed for TCO2 using an enzymatic technique (in
      the reference laboratory) and direct measurement using an electrode (in the local
      laboratory). The blood test results for TCO2 sent to the reference laboratory
      (18.7 +/- 0.8 mEq/L) were significantly lower than samples assayed in our local
      laboratory (22.2 +/- 0.7 mEq/L). In conclusion, recognition of the differences in
      assays used in the laboratory for routine bicarbonate measurements is important
      in defining the magnitude of metabolic acidosis and in helping to dictate
      appropriate therapy.

PMID- 9158208
TI  - Long-term effects of intravenous calcitriol therapy on the control of secondary
      hyperparathyroidism.
AB  - Although high-dose intravenous calcitriol has been shown to be effective in
      suppressing parathyroid hormone (PTH) secretion in dialysis patients with
      secondary hyperparathyroidism, an increasing number of patients is refractory to
      treatment. Only a few studies have evaluated the factors that can predict a
      favorable response to calcitriol, but contrasting results have been reported.
      This study was performed to evaluate the effect of high-dose intravenous
      calcitriol on parathyroid function and to investigate the factors that can
      predict a favorable response to treatment. Thirty-five dialysis patients were
      selected for intravenous calcitriol treatment (2 microg after dialysis for 12
      months) because of increased PTH levels (>325 pg/mL). Before starting the
      treatment, the set point of calcium and the PTH-ionized calcium (ICa) curve was
      evaluated in each patient by inducing hypocalcemia and, 1 week later,
      hypercalcemia to maximally stimulate or inhibit PTH secretion. Parathyroid glands
      were assessed by high-resolution color Doppler ultrasonography. Throughout the
      study, calcium carbonate or acetate dosage was modified to maintain serum
      phosphate less than 5.5 mg/dL. Hypercalcemia was managed by reducing dialysate
      calcium to 5 mg/dL and, if necessary, calcitriol dose. The therapeutic goal was
      to reduce PTH levels below 260 pg/mL while maintaining normocalcemia. The
      patients who achieved the therapeutic goal were considered responders. Taking the
      data from the 35 patients together, we observed a significant decrease (P < 0.01)
      in alkaline phosphatase (from 252 +/- 106 IU/L to 194 +/- 81 IU/L) and PTH (from
      578 +/- 231 pg/mL to 408 +/- 291 pg/mL), and a significant increase in serum ICa
      (from 5.1 +/- 0.2 mg/dL to 5.3 +/- 0.2 mg/dL; P < 0.001) after calcitriol
      therapy. PTH changes after therapy were not correlated to serum ICa changes,
      serum phosphate levels during treatment, and calcitriol dose. The response to
      therapy was heterogeneous because PTH levels markedly decreased over the
      treatment period in 18 responsive patients, whereas they increased or remained
      unchanged in 14 of 17 nonresponders. In three additional refractory patients,
      there was a decline in PTH of 20% to 35%, but this decline was associated with
      hypercalcemia. Pretreatment parathyroid gland size, serum ICa, PTH, maximal PTH
      induced by hypocalcemia, minimal PTH induced by hypercalcemia, the set point of
      ICa, and the ICa levels at which maximal PTH secretion and inhibition occurred
      were higher in the 17 refractory patients than in the 18 responsive patients.
      However, logistic regression analysis showed that among these parathyroid
      function parameters, the only significant predictors of a favorable response to
      calcitriol therapy were the parathyroid gland size and the set point of ICa.
      Throughout the study, serum phosphate and calcitriol dose were comparable in the
      two groups. In conclusion, the response to intravenous calcitriol therapy in
      dialysis patients with secondary hyperparathyroidism is heterogeneous, consisting
      of patients who are either responsive or refractory to treatment; refractoriness
      can be predicted by parathyroid volume and calcium set point.

PMID- 9158209
TI  - Echo color Doppler imaging of carotid vessels in hemodialysis patients: evidence
      of high levels of atherosclerotic lesions.
AB  - Cardiovascular disease is the major cause of death in patients with end-stage
      renal disease, and the incidence of atherosclerosis-related complications is
      significantly higher in dialysis patients than in nonuremic controls. This study
      aimed at evaluating atherosclerotic involvement of carotid vessels in
      hemodialysis patients and in a group of subjects with a similar cardiovascular
      risk factor pattern using echo color Doppler ultrasonography. Carotid lesions
      have been evaluated, taking into account plaque characters (surface,
      echogenicity), the most severe luminal narrowing, and the number of vessels
      involved. A large number of vascular plaques has been observed in uremic
      patients: 73.8% versus 44% in the control group (chi square test = 10.98; P <
      0.01). A high prevalence of carotid lesions has been found in both patients and
      controls with clinical evidence of cardiovascular complications. Finally, we have
      considered the presence of carotid lesions with a topographic evaluation. The
      presence of atheromatous lesions in hemodialysis patients compared with control
      subjects was statistically significant different in all the vessels except common
      carotid (internal carotid: chi-square test = 8.59, P < 0.01; external carotid;
      chi-square test = 13.46, P < 0.01; bulb chi-square test = 7.90; P < 0.01). Our
      data clearly show that the hemodialysis population suffers from a higher degree
      of atherosclerosis than age- and sex-matched controls with similar cardiovascular
      risk patterns, suggesting that the uremic state in conservative and substitutive
      treatment per se may contribute to "advanced" atherosclerosis. However, this does
      not enable us to state that hemodialysis accelerates atherosclerosis. In fact,
      the progression of atherosclerosis might be related to atherogenic factors
      operative before regular dialysis.

PMID- 9158210
TI  - Use of low-dose low molecular weight heparin in hemodialysis.
AB  - We investigated the lowest effective dosage of low molecular weight (LMW) heparin
      for hemodialysis in comparison to unfractionated (UF) heparin. Initial
      hemodialysis sessions were undertaken in 10 uremic patients with UF heparin of
      the dose habitually required for each patient. Four-hour hemodialysis sessions
      were then undertaken with LMW heparin (nadroparin) in a single bolus (200 anti-Xa
      unit Institut Choay/kg [aXaU IC/kg], 175 aXaU IC/kg, 150 aXaU IC/kg, or 125 aXaU
      IC/kg; two sessions for each dosage). Anti-Xa levels and activated partial
      thromboplastin time (APTT) were monitored hourly during dialysis. Fiber bundle
      volume of dialyzer was measured before and after dialysis. Urea clearance was
      determined at the onset and completion of dialysis. There were no episodes of
      excessive bleeding, clotting of dialyzers, or clots in air traps with UF heparin
      or LMW heparin. A 35% increase in APTT above baseline was observed in all
      dialysis sessions 1 hour after LMW heparin bolus, but the APTT decreased rapidly
      thereafter. The anti-Xa levels exceeded 0.5 U/mL for all sessions using LMW
      heparin irrespective of the dosage. No significant reduction of urea clearance
      was found in dialysis with either UF or LMW heparin. No reduction of fiber bundle
      volume of dialyzer was observed in dialysis with either UF or LMW heparin,
      although a small reduction (3%) was observed in dialysis with LMW heparin at 125
      aXaU IC/kg. We concluded that the use of LMW heparin for hemodialysis is safe and
      effective as compared with UF heparin. The lowest effective dosage can be reduced
      to 125 aXaU IC/kg in high-risk patients to reduce hemorrhagic complications.

PMID- 9158211
TI  - Screening for extreme postdialysis urea rebound using the Smye method: patients
      with access recirculation identified when a slow flow method is not used to draw
      the postdialysis blood.
AB  - To look for patients with extreme urea rebound, we drew intradialytic samples one
      third of the way into dialysis during routine modeling for 3 months. The samples
      taken postdialysis were obtained after stopping the blood pump, without any slow
      flow period. Using the Smye equations, the intradialytic urea level was used to
      predict urea rebound, expressed as Kt/V-equilibrated minus Kt/V-single pool
      (deltaKt/V). Results were averaged for the 3-month period in 369 patients. Mean
      estimated deltaKt/V was -0.20 +/- 0.13, which was similar to but slightly higher
      than the predicted value (-0.6 x K/V + 0.03) of -0.19 +/- 0.04. In 27 patients,
      extreme rebound (mean deltaKt/V < -0.40) was found. Sixteen of these patients
      consented to further study, but only after access revision in four patients. In
      these patients, additional slow flow samples after 15 seconds and 2 minutes of
      slow flow, respectively, were drawn one third of the way into dialysis and
      postdialysis, and a sample was drawn 30 minutes after dialysis. On restudy,
      postdialysis rebound was still high with full flow samples deltaKt/V = -0.40 +/-
      25, but was much lower (-0.18 +/- 0.07) and similar to predicted rebound (-0.19
      +/- 0.05; P = NS) when based on 15-second slow flow samples. Eight of the 16 had
      marked (>15%) access recirculation by urea sampling, and deltaKt/V based on full
      flow post samples correlated with access recirculation (r = -0.91). The results
      suggest that the Smye method is valuable for identifying patients with aberrantly
      large postdialysis rebound values. When the postdialysis samples are drawn
      without an antecedent slow flow period, most patients with extreme rebound values
      turn out to have marked access recirculation.

PMID- 9158212
TI  - Postdialysis fatigue.
AB  - To clarify the demographic and clinicolaboratory features of postdialysis fatigue
      (PDF), we enrolled 85 patients on maintenance hemodialysis in a cross-sectional
      study using validated questionnaires and chart review. Forty-three patients
      complained of fatigue after dialysis. On formal testing using the Kidney Disease
      Questionnaire, the PDF group had statistically greater severity of fatigue and
      somatic complaints than the group of patients without subjective fatigue (P =
      0.03 and 0.04, respectively). On a scale measuring intensity of fatigue (1 =
      least to 5 = worst), the PDF group average was 3.4 +/- 1.2. PDF subjects reported
      that 80% +/- 25% of dialysis treatments were followed by fatigue symptoms. In 28
      (65%) of patients, the symptoms started with the first dialysis treatment. They
      reported needing an average of 4.8 hours of rest or sleep to overcome the fatigue
      symptoms (range, 0 to 24 hours). There were no significant differences between
      patients with and without PDF in the following parameters: age; sex; type of
      renal disease; presence of diabetes mellitus, heart disease (congestive,
      ischemic), or chronic obstructive lung disease; blood pressure response to
      dialysis; type or adequacy of dialysis regimen; hematocrit; electrolytes; blood
      urea nitrogen; creatinine; cholesterol; albumin; parathyroid hormone; ejection
      fraction; and use of antihistamines, benzodiazepines, and narcotics. In the
      fatigue group, there was significantly greater use of antihypertensive
      medications known to have fatigue as a side effect (P = 0.007). Depression was
      more common in the fatigue group by Beck Depression score (11.6 +/- 8.0 v 7.8 +/-
      6.3; P = 0.02). We conclude that (1) postdialysis fatigue is a common, often
      incapacitating symptom in patients on chronic extracorporeal dialysis; (2) no
      routinely measured parameter of clinical or dialytic function appears to predict
      postdialysis fatigue; and (3) depression is highly associated with postdialysis
      fatigue, but the cause-effect relationship is unclear.

PMID- 9158213
TI  - Hypertension in the hemodialysis population: any relation to one-year survival?
AB  - Few studies have quantified the effect of hypertension on survival in the
      hemodialysis population. We report the effect of hypertension on 1-year survival
      in 649 hemodialysis patients (89% black). In univariate analysis, hypertension
      was associated with improved 1-year survival (relative risk [RR], 0.48; P = 0.002
      compared with normotensive patients). This effect of hypertension was mostly
      caused by the associated antihypertensive treatment because untreated
      hypertensive patients had survival rates equal to normotensive patients (RR,
      0.87; P = 0.70). On the other hand, treated hypertensive patients fared better
      than normotensive patients (RR, 0.41; P = 0.0006). This was also true in
      multivariate analysis, in which antihypertensive treatment was associated with
      reduced RR (RR, 0.55; P = 0.02) whereas the level of blood pressure per se was
      insignificant (RR, 0.99; P = 0.63 per 1 mm Hg increase in predialysis mean
      arterial pressure). Other factors of significance in multivariate analysis
      included age (RR, 1.03/y; P = 0.0004), serum albumin (RR, 0.38/g; P = 0.002), and
      diabetes mellitus (RR, 1.58; P = 0.06). Our study suggests that antihypertensive
      treatment has a favorable effect on survival in the hemodialysis population
      irrespective of the level of blood pressure control.

PMID- 9158214
TI  - Modeling mortality risk in hemodialysis patients using laboratory values as time
      dependent covariates.
AB  - Proportional hazards analyses assume that the magnitude of mortality risk for a
      predictor variable remains proportional over time. In a time-dependent model, the
      explanatory variable violates this assumption, and repeat observations are
      required to accommodate the change in risk that occurs over time. Using a
      retrospective cohort design, we tested the following laboratory values for a time
      by-covariate interaction: hematocrit (HCT), serum albumin (ALB), and serum
      creatinine (CR). A random sample of 4,083 hemodialysis patients whose specimens
      were analyzed in a central laboratory over a 3-year period served as the study
      group. Using the baseline observation, we discovered significant probability
      values for the interaction terms TIME*CR (P = 0.013) and TIME*ALB (P < 0.01). The
      beta coefficient for TIME*HCT was not significant, indicating that the
      proportional hazard assumption was not violated by this covariate. Based on these
      results, we fitted a multivariate regression model containing two time-dependent
      covariates (CR and ALB) using a data structure that incorporated repeat
      observations of these laboratory values. Patients with high ALB levels
      experienced the lowest mortality risk. Similarly, serum CR levels were higher in
      long-term survivors. This analysis verifies the clinical importance of monitoring
      ALB and CR levels over time and the hazard of using a single laboratory
      observation to make long-term projections. Additionally, the predictive values of
      the time-dependent covariates ALB and CR affirm the significance of nutritional
      approaches directed toward maintaining visceral and somatic protein content
      throughout renal replacement therapy.

PMID- 9158215
TI  - Optimal treatment and long-term outcome of tuberculous peritonitis complicating
      continuous ambulatory peritoneal dialysis.
AB  - A retrospective study of the treatment and short- and long-term outcomes of
      tuberculous peritonitis (TBP) complicating continuous ambulatory peritoneal
      dialysis (CAPD) among our dialysis patients over a 6-year period was performed.
      Ten cases of TBP complicating CAPD were identified among 601 dialysis patients
      between January 1988 and December 1994. There were four male and six female
      patients. The most common clinical features were abdominal pain, fever, and
      cloudy peritoneal fluid (PDF). Two patients had concurrent bacterial peritonitis.
      Extraperitoneal tuberculosis was not observed. The majority of the patients
      showed neutrophil predominance in the PDF. Only one patient had a positive acid
      fast bacilli smear of the PDF. The acid-fast bacilli culture of the PDF was
      positive in all patients. The patients were treated with isoniazid, rifampicin,
      and pyrazinamide for 9 to 12 months (mean, 11 months). Continuous ambulatory
      peritoneal dialysis was continued in all patients. Two patients died, one from
      multiorgan failure at 2 months and the other from sudden cardiac death at 9
      months. Two patients were converted to hemodialysis at 3 months. Six patients
      continued to receive CAPD after completion of the antituberculous treatment. Four
      of these six patients were still alive 5 years after the TBP. Three patients were
      still undergoing CAPD with satisfactory ultrafiltration and solute clearance.
      None of the patients developed relapse of TBP. We concluded that (1) TBP is a
      rare but important complication of CAPD, (2) removal of the Tenckhoff catheter is
      not mandatory in the management of TBP complicating CAPD, and (3) long-term
      continuation of CAPD is possible after TBP.

PMID- 9158216
TI  - Prevalence of hepatitis C in patients with idiopathic glomerulopathies in native
      and transplant kidneys.
AB  - Previous studies suggest that there is an association between hepatitis C (HCV)
      infection and glomerular diseases in native and transplanted kidneys. However,
      the data are controversial. To reexamine this issue, we determined the prevalence
      of serum anti-HCV antibodies in patients with glomerulopathies of native kidneys
      (n = 105) and in patients with acute and chronic transplant glomerulopathy (TxGN)
      (n = 62). Compared with a control group of patients with diabetic nephropathy (n
      = 37, 0% HCV+), the prevalence of HCV antibodies was significantly higher in
      patients with focal glomerulosclerosis (FGS) (4 of 32, 13%, P = 0.04 by chi
      square), but not in patients with membranous nephropathy (MGN) (1 of 19, 5%) or
      in patients with membranoproliferative glomerulonephritis (MPGN) (2 of 17, 12%).
      All of the patients with positive HCV serology had histories of intravenous (IV)
      drug use. Thus, HCV serology was negative in all of the patients with native
      glomerulopathies without histories of IV drug use. Compared with a group of 105
      transplant patients without TxGN (1.8% HCV+), the prevalence of HCV antibodies
      was significantly higher in patients with acute (A)TxGN (12 or 41: 29%. P =
      0.0004) and in patients with chronic (C)TxGN (9 of 27: 33%. P = 0.0004). Compared
      with controls, patients with ATxGN also had a significantly higher prevalence of
      serum immunoglobulin (Ig) M antibodies to cytomegalovirus (CMV) (3% and 26% of
      patients, respectively, P = 0.0004). However, there were no statistical
      associations between HCV and CMV serologies. These results do not support the
      postulate that HCV infection is associated with idiopathic native
      glomerulopathies; instead, the data suggest that the presence of HCV positivity
      in these patients can be explained by the inclusion of patients with a history of
      IV drug use. In contrast, these studies demonstrate for the first time an
      association between HCV infection and transplant glomerulopathies.

PMID- 9158217
TI  - An Italian family with autosomal dominant polycystic kidney disease unlinked to
      either the PKD1 or PKD2 gene.
AB  - We describe a family with autosomal dominant polycystic kidney disease in which
      molecular typing with closely linked markers for the PKD1 and PKD2 genes
      indicated absence of linkage. Thus, a third still unknown locus appears likely to
      be involved in disease development. This is the fourth "PKD3-linked" family
      described to date and the first from Italy.

PMID- 9158219
TI  - Acute massive gentamicin intoxication in a patient with end-stage renal disease.
AB  - A 65-year-old man with end-stage renal disease on continuous ambulatory
      peritoneal dialysis accidentally received an acute massive overdose of gentamicin
      as a treatment of peritonitis. The patient developed acute vestibular dysfunction
      and hearing loss following the overdose. His serum gentamicin had reached the
      extremely toxic level of 220 microg/mL. To remove the gentamicin, the patient
      received hemodialysis and hemoperfusion immediately. This was followed by two
      more courses of hemodialysis during the following 2 days. The gentamicin level
      was brought down to 10 microg/mL after the third hemodialysis. Moderate and
      persistent high-frequency hearing loss was documented with serial audiograms. The
      patient made a gradual but incomplete recovery from the vestibular dysfunction.
      The complications of gentamicin toxicity and its management are discussed with
      respect to our patient.

PMID- 9158218
TI  - Sjogren's syndrome with acute renal failure caused by renal pseudolymphoma.
AB  - A 56-year-old man with Sjogren's syndrome was found to have acute renal failure.
      Immunopathologic analysis of renal biopsy specimens showed polyclonal lymphocytic
      interstitial infiltration. DNA analysis of the T-cell receptor and the heavy
      chain immunoglobulin genes showed a polyclonal pattern of gene rearrangements.
      Renal failure caused by this pseudolymphoma regressed dramatically with steroid
      therapy. This is the first reported case of proven renal pseudolymphoma that
      regressed with steroid therapy.

PMID- 9158220
TI  - Video-assisted talc pleurodesis in the management of pleural effusion secondary
      to continuous ambulatory peritoneal dialysis: a report of three cases.
AB  - Continuous ambulatory peritoneal dialysis (CAPD) is an effective treatment for
      end-stage renal disease. Hydrothorax secondary to pleuroperitoneal communication
      is an unusual complication of CAPD, with persistence or recurrence requiring
      alternate forms of dialysis. We have recently managed three patients with CAPD
      induced right hydrothorax secondary to such communications. Earlier treatment
      methods have included thoracentesis or tube thoracostomy with chemical
      pleurodesis and even thoracotomy with attempts to locate and close the
      communication. We used a new approach consisting of video-assisted thoracic
      surgery and direct talc poudrage. All patients were successfully returned to
      CAPD; one patient required a repeat procedure after an initial recurrence. Video
      assisted thoracic surgery with talc poudrage is an effective and safe procedure
      with minimal morbidity for management of hydrothorax secondary to CAPD. This
      procedure allows identification of diaphragmatic defects amenable to repair and
      talc placement under direct visualization, allowing even distribution over the
      inferior surface of the lung.

PMID- 9158221
TI  - Salt-sensitive hypertension: lessons from animal models.
AB  - The underlying etiology of salt-sensitive hypertension has been elusive, in part
      because the term represents a syndrome rather than a specific disease entity and
      in part because of the difficulty in completely defining the characteristics of
      the syndrome. The introduction of inbred models of salt-sensitive hypertension
      has facilitated understanding blood pressure response to dietary salt. Careful
      examination of one of these models, the Dahl/Rapp rat, has shown that the L
      arginine:nitric acid (NO) pathway is integrally involved in production of
      hypertension in response to an increase in dietary salt. This review provides an
      overview of NO, salt sensitivity, and the role of NO in the pathogenesis of salt
      sensitive hypertension.

PMID- 9158222
TI  - Commentary on the National Kidney Foundation position paper on analgesics and the
      kidney.

PMID- 9158223
TI  - Regular measurement of anti-GBM antibodies in Goodpasture's disease?

PMID- 9158224
TI  - Withdrawing respect from the tobacco trade.

PMID- 9158225
TI  - Journal interview--39. Conversation with Senator Harold Hughes.

PMID- 9158226
TI  - Validation of the amphetamine dependence syndrome and the SAmDQ.
AB  - The severity of Amphetamine Dependence Questionnaire (SAmDQ) was administered to
      132 subjects who were amphetamine dependent by DSM-III-R criteria. The structural
      characteristics of the questionnaire were examined and findings compared with
      those reported previously for both the SAmDQ and its forebear, the SODQ. There
      was a high degree of consistency in the present psychometric analyses and those
      reported earlier; and comparisons between samples of differing dependence
      severities indicated that the SAmDQ is capable of discriminating between these
      groups. The findings support the existence of an amphetamine dependence syndrome,
      and help to explicate the dimensions underlying such a syndrome and the
      characteristics of the population in which it may be manifest.

PMID- 9158227
TI  - Decreased nociceptive sensitivity: a biological risk marker for opiate
      dependence?
AB  - In recent studies using a cold pressor test we could show that former opiate
      addicts are persistently less pain-sensitive than healthy controls, indicating a
      neurophysiologic dysfunction in these patients. In the present study we addressed
      the issue of whether this dysfunction was caused by the drug abuse or already
      existed prior to the heroin addiction, and whether it is restricted to pain
      sensitivity or affects somatosensory or nociceptive sensitivity in general. After
      validating the method we obtained retrospective ratings for the pain, cold and
      warmth sensitivity for the time before addiction, during addiction and during
      detoxification. Ex-addicts perceive themselves less pain- and cold-sensitive than
      healthy controls, and no difference was detectable between the pre-addiction and
      the rehabilitation ratings, although nociceptive sensitivity is highly increased
      during detoxification. Warmth sensitivity was not different to healthy controls
      and was not affected by drug withdrawal. Our findings suggest that a decreased
      nociceptive sensitivity may already precede opiate addiction pointing to
      physiological dysfunctions in heroin pre-addicts.

PMID- 9158228
TI  - Hepatitis C virus serology in parenteral drug users with chronic liver disease.
AB  - Chronic liver disease is a common complication of parenteral drug use, and liver
      cirrhosis is frequently seen in users of both parenteral drugs and alcohol. In
      1978-83, we studied 88 parenteral drug users with sufficient evidence of chronic
      liver disease to warrant liver biopsy. Current alcohol abuse was noted in 63
      (72%), and six (7%) were former alcohol abusers. Cirrhosis was found in 33 (38%).
      Hepatitis C antibody (anti-HCV) was detected in 86 (98%). Also, 40 of the anti
      HCV positive sera were tested with recombinant immunoblot assay and all of these
      were reactive. All but one of the 31 patients with anti-HCV and cirrhosis were
      alcohol abusers. We conclude that parenteral drug users with chronic liver
      disease almost always have evidence of HCV infection.

PMID- 9158229
TI  - An Australian profile on the use of cocaine.
AB  - Data collected on cocaine in Australia in the mid to late 1980s, when law
      enforcement and treatment centres were concerned with possible increases in
      cocaine use, indicated a low prevalence of use. This article reports findings
      from the Australian component of the 1993-94 World Health Organization study
      entitled "Initiative on Cocaine", which provides an updated analysis of cocaine
      use patterns and consequences. The two components of this study were a "country
      profile" which summarized existing health, law enforcement and survey data on
      cocaine use from national, regional and city level records, and a key informant
      study which consisted of interviews with people from Sydney and Melbourne who
      were familiar with cocaine use through personal, professional and observational
      experience. Findings show that the prevalence of cocaine use has remained low
      among the general population in Australia (around 2%), and few people present to
      treatment services with primary cocaine problems or are arrested. However, the
      use of cocaine seems to have increased among inner Sydney injecting drug users.
      There have also been indications of larger police seizures of cocaine, reflecting
      a possible increase in availability. Recommendations are made to provide relevant
      interventions and continually monitor patterns of cocaine use, particularly among
      at-risk groups.

PMID- 9158230
TI  - Life-time problem drinking and psychiatric co-morbidity among Ontario women.
AB  - Women problem drinkers in the community, aged 15-64 years, with and without life
      time psychiatric co-morbidity were compared to examine the association of this co
      morbidity with alcohol consumption patterns, course and chronicity of problem
      drinking, treatment service utilization and other substance use and misuse. The
      women problem drinkers were also compared with non-problem drinkers on substance
      use patterns and utilization of services. The study employs data from the Mental
      Health Supplement to the Ontario Health Survey, a province-wide household
      population study. The University of Michigan Composite International Diagnostic
      Interview (UM-CIDI) was administered by trained lay interviewers and subsequently
      World Health Organization computer algorithms were used to generate DSM-III-R
      diagnoses based on the interview responses. Multiple logistic regression analysis
      indicated that psychiatric co-morbidity was associated with less education,
      earlier onset of problem drinking and one indicator of binge drinking. Co
      morbidity also greatly increased the chances of women problem drinkers having
      sought mental health treatment. Women problem drinkers were significantly younger
      (about 7 years) than women in the general population, perhaps an indicator of an
      increased mortality rate.

PMID- 9158231
TI  - The Alcohol Use Disorders Identification Test (AUDIT) as a screen for at-risk
      drinking in primary care patients of different racial/ethnic backgrounds.
AB  - This study examined the operating characteristics of the Alcohol Use Disorders
      Identification Test (AUDIT) as a screen for "at-risk" drinking in a multi-ethnic
      sample of primary care patients, from a family practice center located in the
      southwestern United States. A probability sample of 1,333 family medicine
      patients, stratified by gender and racial/ethnic background (white, African
      American and Mexican-American) completed the AUDIT, followed by the Alcohol Use
      Disorders and Associated Disabilities Interview Schedule (AUDADIS) to determine
      ICD-10 diagnoses. Indicators of hazardous alcohol use and alcohol-related
      problems were included as measures of "at-risk" drinking. Despite differences in
      the spectrum of alcohol problems across patient subgroups, there was no evidence
      of gender or racial/ethnic bias in the AUDIT as indicated by Receiver Operating
      Characteristic Curve analysis. Excluding abstainers from the analysis and little
      impact on screening efficacy. In this population, the AUDIT appears to be an
      unbiased measure of "at-risk" drinking.

PMID- 9158232
TI  - Subgroups of smokers with different success rates after use of transdermal
      nicotine.
AB  - To identify subgroups of smokers with different success rates, we applied "tree
      structured survival analysis" (TSSA) to data from a previously published trial of
      transdermal nicotine. The subjects who received active treatment (14 mg patch, n
      = 275, or the 21 mg patch, n = 262) constituted the sample for this analysis.
      Using age, gender, the Fagerstrom Tolerance Questionnaire (FTQ), motivation to
      quit, number of cigarettes smoked at baseline, and body mass index (BMI) as
      classification variables, TSSA identified two subgroups within the 14 mg patch
      group and four subgroups of smokers within the 21 mg patch group. Among those
      receiving the 14 mg patch, individuals with a BMI greater than 26.4 kg/m2
      relapsed sooner than did those with a BMI less than or equal to this value.
      Within the 21 mg patch group, the survival curve for males was significantly
      different from that observed in females, with males experiencing a longer time to
      relapse after treatment than did females. Among females, those with a higher
      motivation to quit relapsed more slowly than did those women with less motivation
      to quit. This information may be helpful to clinicians seeking to match specific
      patients to specific treatments with traditional nicotine in order to maximize
      treatment outcomes.

PMID- 9158233
TI  - Incidence of needlestick injuries among people who inject.

PMID- 9158234
TI  - Methadone kills more people than heroin. A reply to Newcombe.

PMID- 9158235
TI  - An historical error in the tribute to the late Mark Keller.

PMID- 9158236
TI  - Ozone degradation of residual carbon in biological samples using microwave
      irradiation.
AB  - In an attempt to produce complete oxidation of a biological matrix, bovine liver,
      ozone was investigated as an additional, potentially non-contaminating, oxidizing
      reagent after nitric acid digestion. Experiments were carried out to determine
      the decomposition efficiency of residual carbon species, primarily o-, m- and p
      nitrobenzoic acids (NBAs), using ozone. The NBAs were degraded by purging sample
      digests with ozone, while heating the solutions with microwave energy at
      atmospheric pressure. The effects of the degradation temperature and solution pH
      on the ozonation of NBAs were determined. Solid phase extraction (C18) was used
      to extract NBAs from the acid digestate solutions prior to HPLC analysis.
      Reversed phase HPLC was used to determine NBA concentrations in digest solutions.
      After 2.5 h of purging ozone at 80 degrees C, 33.65 +/- 3.80% o-NBA degradation,
      19.39 +/- 1.74% m-NBA degradation, and 26.47 +/- 3.36% p-NBA degradation were
      obtained.

PMID- 9158237
TI  - Determination of organophosphorus pesticides in foods using an accelerated
      solvent extraction system.
AB  - Residual organophosphorus pesticides in foods were determined by accelerated
      solvent extraction (ASE), gel permeation chromatography and GC-FPD. Pesticides
      were extracted at 100 degrees C under 1500 psi pressure in less than 20 min. Wet
      samples were extracted after mixing with Extrelut drying agent. Four foods were
      spiked with 19 pesticides at 0.1 ppm or less. The average recoveries of these
      pesticides were 80-90% and the precision was < 10%. Both methamidophos and
      acephate gave 37-50% recoveries and 6-40% precision. These results suggested that
      ASE can be used to extract residues of organophosphorus pesticides in foods.

PMID- 9158238
TI  - Simultaneous spectrofluorimetric determination of selenium (IV) and (VI) by flow
      injection analysis.
AB  - A simple, sensitive, highly selective, automatic spectrofluorimetric method for
      the simultaneous determination of selenium (IV) and (VI) as selenite-selenate by
      flow injection analysis (FIA) has been developed. The method is based on the
      selective oxidation of the non-fluorescent reagent 2-(alpha
      pyridyl)thioquinaldinamide (PTQA) in acidic solution (1.5-3.0 M H2SO4) by SeIV to
      give an intensely fluorescent oxidation product (lambda ex =350 nm; lambda em =
      500nm). Selenium (VI) is reduced on-line to SeIV, in a reduction coil installed
      in a photo-reactor, which is then treated with PTQA and the fluorescene due to
      the sum of SeIV and SeVI is measured; SeVi is determined from the difference in
      fluorescence values. Various analytical parameters, such as effect of acidity,
      flow rate, sample size, dispersion coefficient, temperature, reagent
      concentration and interfering species were studied. The photo-reduction
      conditions were optimized, with an FIA procedure, for SeVI on the basis of its
      reduction efficiency. The calibration graphs were rectilinear for 0.1-2.4
      micrograms ml-1 of SeVI and 10 ng ml-1-2.2 micrograms ml-1 of SeIV, respectively.
      The method was applied to the determination of Se in several Standard Reference
      Materials (alloy, sediments and tea), as well as in some environmental waters
      (tap and surface water), food samples (flour and egg), a biological sample (human
      hair), soil sample and in synthetic mixtures. Up to 25 samples per hour can be
      analysed with an RSD approximately 0.1-2%.

PMID- 9158239
TI  - Direct determination of amiloride in urine using isopotential fluorimetry.
AB  - A method for the determination of amiloride at concentrations between 15 and 152
      ng ml-1 by means of matrix isopotential synchronous fluorescence spectrometry and
      derivative techniques is proposed. This method is useful for the determination of
      compounds in samples with unknown background fluorescence without the need for
      tedious pre-separation. As amiloride is widely used as a doping substance in
      sport, the method was successfully applied to the determination of amiloride in
      urine. To obtain maximum sensitivity and adequate selectivity, factors affecting
      fluorescence intensity were studied in the amiloride band centered and lambda ex
      = 362 nm and lambda em = 415 nm. As a result, the determination was performed in
      an ethanol-water (1 + 1, v/v) medium at pH 6.3, adjusted by using sodium citrate
      citric acid (0.1 M) as buffer solution. The concentration of amiloride in urine
      samples can be calculated by recording its total luminescence spectrum and
      applying the isopotential trajectory of the urine that cuts the selected band of
      amiloride. The unknown analytical signal of urine is eliminated in the MISF
      spectrum obtained, be means of its first derivative. A calibration graph was
      constructed by measuring first derivative values at lambda ex = 357nm and lambda
      em = 392 nm. Analytical parameters of the proposed method were calculated
      according to the error propagation theory. The sensitivity, repeatability,
      reproducibility and limit of determination achieved with the proposed method are
      adequate for the determination of amiloride in urine.

PMID- 9158240
TI  - Phosphorimetric determination of dipyridamole in pharmaceutical preparations.
AB  - Room temperature phosphorescence was applied to the determination of dipyridamole
      in pharmaceutical preparations. The response was linear in the concentration
      range 100-1600 ng ml-1. The use of phosphorescence enhancers such as thallium(I)
      nitrate (external heavy atom), sodium dodecyl sulfate (microemulsion stabilizer)
      and sodium sulfite (deoxygenation agent) was studied and optimized to obtain
      maximum sensitivity and adequate selectivity. The determination was performed in
      0.026 M sodium dodecyl sulfate, 0.0156 M thallium nitrate and 0.02 M sodium
      sulfite. The pH value was 11.5, adjusted by adding sodium hydroxide. The
      phosphorescence was totally developed in 15 min, after that the intensity was
      measured at lambda ex = 303 nm and lambda em = 616 nm. The recovery of the method
      was tested on commercial formulations containing dipyridamole. The recoveries
      obtained were 94.67 +/- 0.58% for Persantin and 96.75 +/- 1.37% for Asasantin.
      The overall least squares regression method was applied to find the most exact
      straight line that fits the experimental data. The detection limit according to
      the error propagation theory was 16.4 ng ml-1. The repeatability and relative
      standard deviation were also determined according to this theory.

PMID- 9158241
TI  - Enzymic method for the spectrophotometric determination of benzoic acid in soy
      sauce and pickles.
AB  - A simple spectrophotometric method for the determination of benzoic acid is
      described. Benzoic acid is measured enzymically through its reaction with
      benzoate 4-hydroxylase coupled with NADPH and O2. The entire enzymic procedure
      required 20 min to complete. The method greatly simplifies the procedure for
      benzoic acid determination and permits the routine inspection of a number of
      samples with very little laboratory equipment. The method was compared with HPLC
      and satisfactory agreement was achieved.

PMID- 9158242
TI  - Determination of complex mixtures of airborne isocyanates and amines. Part 3.
      Methylenediphenyl diisocyanate, methylenediphenylamino isocyanate and
      methylenediphenyldiamine and structural analogues after thermal degradation of
      polyurethane.
AB  - A method is presented for the determination of isocyanates in polymeric
      methylenediphenyl diisocyanate (MDI) and related compounds formed during the
      thermal decomposition of polyurethane (PUR). Derivatization of isocyanates was
      performed in impinger flasks containing dibutylamine (DBA) with the formation of
      urea derivatives. Compounds containing amine groups were then derivatized with
      ethyl chloroformate (ET to give urethane derivatives. Reversed-phase liquid
      chromatography, with a gradient flow rate of 40 milligrams min-1 and mass
      spectrometry in the electrospray mode monitoring positive ions was studied.
      Injection volumes of up to 10 milligrams of the sample were made possible by
      using column focusing. 1,5-Naphthyldiisocyanate-DBA and 1,5-naphthyldiamine-ET
      derivatives were used as internal standards. Virtually linear calibration curves
      were obtained for 4,4'-MDI-DBA and 4,4'-methylenediphenyldiamine-ET (MDA-ET) and
      the correlation coefficients were 0.9952-0.9964 (n = 14). The precision for five
      injections of samples spiked with 4,4'-MDA-ET, and 4,4'-MDI-DBA ar concentrations
      of 50 nmol ml-1 was 2.76 and 2.55%, respectively. The instrumental detection
      limit, defined as three times the noise, was 4 fmol of MDI-DBA and 50 fmol of MDA
      ET injected. In chromatograms of polymeric MDI derivatized with diethylamine,
      dipropylamine and DBA, the presence of several structural isomers and analogues
      in polymeric MDI was demonstrated. In the chromatograms of thermal decomposition
      products of MDI-PUR, in addition to isocyanates, related amino isocyanates and
      amines were also observed.

PMID- 9158243
TI  - Optosensor for cinchona alkaloids with C18 silica gel as a substrate.
AB  - A flow-through optosensor for cinchona alkaloids with C18 silica gel as a
      substrate is proposed. The sensor is developed in conjunction with a flow
      injection analysis system and is based on the retention of the cinchona alkaloids
      on a C18 column and the enhancement of their fluorescence. The analytical
      performance characteristics of the proposed sensor for the detection and
      quantification of these alkaloids were as follows: the detection limits of
      quinine, cinchonine, quinidine and cinchonidine were 2.3, 31.6, 2.3 and 31.6 ng
      ml-1, respectively, with relative standard deviations of 0.9% for quinine and
      quinidine (20 ng ml-1, n = 7) and 1.1% for cinchonine and cinchonidine (4.0
      micrograms ml-1, n =7), respectively. Most of the common species did not
      interfere. The recommended method has been successfully tested for determination
      of quinine in pharmaceutical preparations and soft drinks.

PMID- 9158244
TI  - Quality and accreditation in clinical chemistry laboratories analysis in the
      National Health Service.

PMID- 9158245
TI  - Angiographic benefits from lipid-lowering in the clinical context.

PMID- 9158246
TI  - Effect of subclinical lead intoxication on laryngeal cancer.
AB  - In this study we investigated the possible relationship of laryngeal cancer and
      subclinical lead intoxication, using the depression of aminolevulinic acid
      dehydratase (ALAD) activity in blood as indicator. Twenty-six patients with
      laryngeal cancer and 53 normal controls met the criteria to enter the study.
      Blood ALAD activity values in the patients with laryngeal cancer ranged from 27.1
      to 75.3 U/l with a mean of 50.79 U/l. The respective values in the control group
      ranged from 36.2 to 98 U/l with a mean of 59.76 U/l. There was a statistically
      significant difference between the two means (0.001 < p < 0.01), whereas blood
      lead concentrations in all patients were within normal limits. These findings
      support the hypothesis that low level lead intoxication (subclinical blood lead
      levels), from cars, industries and products, may contribute to the risk of
      laryngeal cancer. Further investigation is needed to clarify the exact
      relationship between lead and cancer of the larynx.

PMID- 9158247
TI  - Open access fundholding endoscopy in the private sector.
AB  - We conducted a comparative study of 150 patients referred for endoscopy to an NHS
      hospital and 150 patients referred to an open access scheme in the private sector
      for fundholding GPs. The concept of consultoscopy, whereby a consultant
      gastroenterologist gives an opinion at the same visit as the endoscopy is
      performed, is introduced. Results showed a similar number of normal studies
      (about 40%) were performed in each group, although the number of examinations
      showing serious pathology was significantly higher in the fundholding group (p <
      0.01). Patients seen in the fundholding scheme had less sedation, required fewer
      outpatient appointments, and the GPs were given more advice on further management
      than those seen in the non-fundholding group. We conclude that open access
      endoscopy in the private sector is a workable option and may result in work being
      transferred from NHS hospitals to the private sector unless NHS hospitals review
      their working practices. The concept of consultoscopy is a useful development on
      traditional open access systems.

PMID- 9158248
TI  - Community-acquired lower respiratory tract infection: implementation of an
      antibiotic protocol.
AB  - Enthusiastic formulation of clinical guidelines continues to increase but
      although theoretical difficulties in guideline implementation have been
      recognised, little attention has been paid to their effectiveness in everyday
      clinical practice. The introduction of a protocol for empirical treatment of
      lower respiratory tract infection (PETRI) to an acute medical take-in unit in
      Belfast is described. Early involvement of all relevant staff, preparation of
      user-friendly flow charts, and imaginative publicity, resulted in an initial
      implementation rate of 75%. The role of implementation as a significant rate
      limiting step in the audit cycle is emphasised.

PMID- 9158249
TI  - Iron deficiency anaemia in general practice: presentations and investigations.
AB  - Twenty-six patients over the age of 50 years with proven iron deficiency anaemia
      were identified, investigated and followed up in general practice over a five
      year period. The anaemia was symptomatic in 50% of patients but only 20% had
      symptoms related to the gut. Faecal occult blood testing was positive in five
      patients only and negative tests occurred in three patients with significant
      disease, including one caecal carcinoma. All patients agreed to
      oesophagogastroduodenoscopy (OGD) and fibreoptic sigmoidoscopy carried out on the
      same occasion. In eight patients, significant abnormalities were found on OGD and
      in two patients on sigmoidoscopy. Four patients declined barium enema
      examinations, two of whom had significant OGD abnormalities. Barium enema
      examination of the other 22 patients showed polyposis of the colon and a caecal
      carcinoma and initially missed one carcinoma of the caecum which was found
      subsequently. The likelihood of finding significant disease in iron-deficient
      patients over 50 years of age is high and should be assumed to be due to blood
      loss into the gut. Investigation by OGD, sigmoidoscopy and barium enema in the
      first instance seems warranted and is a condition that can be safely managed by
      the GP.

PMID- 9158250
TI  - Variability in post-operative fluid and electrolyte prescription.
AB  - A four-week retrospective survey of intravenous fluid and electrolyte
      prescriptions on post-operative surgical patients revealed wide variability in
      fluid and electrolyte prescription by medical staff. Median volume of intravenous
      fluid prescribed was 3000 ml (range 1667-5000). Total sodium prescribed varied
      from 0 to 770, median 242 mmol/day), with potassium infrequently added (range 0
      81, median 0 mmol/day). Patients undergoing emergency surgery were prescribed
      more sodium than those undergoing routine procedures (p = 0.0403); 0.9% saline
      was the most common fluid prescribed overall. There was poor correlation between
      serum electrolyte values and the amounts of electrolytes prescribed. Intravenous
      fluid prescription should take into account the post-operative stress response
      which reduces sodium requirements (unless there are other concomitant losses) and
      increases urinary potassium losses. A suitable post-operative 'maintenance' fluid
      is 4% dextrose/0.18% saline with 1-2 g potassium chloride, particularly if serum
      electrolyte levels are not known. Other fluid losses should be replaced with
      equivalent fluids.

PMID- 9158251
TI  - Immunogenicity and tolerability of a trivalent influenza subunit vaccine
      (Influvac) in high-risk children aged 6 months to 4 years.
AB  - Fifty-two children, aged less than 5 years, with chronic lung disease or
      congenital heart disease were entered into a two-centre open study to determine
      the immunogenicity and tolerability of Influvac, a trivalent influenza sub-unit
      vaccine. Seroresponses were determined following two intramuscular vaccinations
      with 0.25 ml of Influvac, four weeks apart. Any local or systemic reaction was
      sought. Seroresponses were age and antigen specific, with children older than 9
      months showing better seroresponses to all three antigens. Both A/Taiwan and
      B/Panama strains met all efficacy criteria. A/Shangdong met two of the three
      criteria: seroconversion and mean geometric titre increase. Local (23%) and
      systemic (48%) reactions following either of the two vaccinations were minor in
      nature and resolved within a few days. The vaccine induced a strong antibody
      response against all three haemagglutinin antigens and was well tolerated. The
      incidence of local and systemic reactions was comparable with those reported in
      healthy adults.

PMID- 9158252
TI  - Acute admissions with atrial fibrillation in a British multiracial hospital
      population.
AB  - To assess the clinical characteristics and management of patients with atrial
      fibrillation (AF), we performed a prospective survey of all acute medical
      admissions over six months to our hospital. Of 7,451 such admissions, 245 had AF
      (110 male, 135 female; mean age 74.4 years). Of these, 213 were Caucasian, 10
      black/Afro-Caribbean and 22 Asian. Complete data were available for 185 patients.
      Of these, 82 had newly diagnosed AF, 83 had previous chronic AF and 20 had
      paroxysmal AF. The main presenting features was dyspnoea, stroke and syncope. A
      history of ischaemic heart disease was present in 64, heart failure in 46,
      hypertension in 51 and rheumatic heart disease in 13, while 31 had a previous
      stroke. Chest X-ray showed cardiomegaly and pulmonary oedema in 121 patients, but
      was normal in 28. Echocardiography showed poor cardiac function in eight patients
      and enlarged left atria in five. Only 28% of those with previously diagnosed AF
      were on anticoagulation. Of the newly diagnosed patients, only 18% were started
      on anticoagulants. Cardioversion was attempted or planned in only 6%. The primary
      diagnosis on discharge was heart failure in 45, stroke in 24 and myocardial
      infarction in 12. AF remains a common arrhythmia among acute medical admissions
      and is commonly associated with heart failure and a high mortality. There is
      still a reluctance to start anticoagulant therapy or to perform cardioversion in
      such patients.

PMID- 9158253
TI  - Impotence and its non-surgical management.
AB  - Impotence is a common symptom which can cause considerable distress to both the
      sufferer and his partner. The use of pharmacotherapy to improve erectile function
      will continue to increase as safe and effective drugs are developed. However,
      restoring erectile function should not be the only treatment objective. It is
      also essential to address personal and emotional factors in the sufferer,
      conflicts in his relationship with his partner, and sexual problems in his
      partner, all of which may be instrumental in causing or maintaining the
      presenting impotence. We advocate a combined approach with appropriate medical
      treatment and sex and couple therapy.

PMID- 9158254
TI  - Current surgical treatment of Dupuytren's disease.
AB  - The practice of surgery for Dupuytren's contracture is changing. Most surgery can
      be carried out under regional or local anaesthesia on a day case basis. Although
      the commonest surgery performed is partial fasciectomy, there is more a
      polarisation developing with minimal surgery (e.g. segmental fasciectomy) for
      early disease and more aggressive surgery (dermofasciectomy) for advanced and
      recurrent disease.

PMID- 9158255
TI  - Interferons in oncology.
AB  - The interferons are natural glycoproteins secreted in response to various
      stimuli, including viral infection. They have antiviral, antiproliferative and
      immunomodulatory effects on different target cell populations. Since recombinant
      human interferons have become available, they have been tested in a wide range of
      malignancies. They are well established in the treatment of hairy cell leukaemia,
      chronic myelogenous leukaemia and multiple myeloma. Although they have documented
      activity against lymphoma, melanoma, renal cell cancer and carcinoid tumours,
      their role in the treatment of these tumours is less clear. In the common solid
      tumours, such as lung cancer and colorectal cancer, the use of interferons
      remains experimental. Here we will summarise their practice applications in
      oncology, using randomised studies where available to establish their place in
      multi-modality treatment. We will not discuss their use as antiviral or
      immunomodulating agents in viral and autoimmune diseases, multiple sclerosis or
      after organ transplantation.

PMID- 9158256
TI  - Optimising the medical management of benign prostatic hyperplasia.
AB  - The ageing population is presenting an increasing demand on future healthcare
      services. In males, prostatic disease is one of the commonest disorders
      contributing to this. Alternatives to surgical intervention have to be considered
      as the preferred option for individuals and whether this be a therapeutic or a
      financial option to be taken. Two major medical alternatives are alpha-blockers
      and 5-alpha reductase inhibitors. The results of such treatment can be very
      beneficial in selected groups of patients. Side-effects with improved drugs
      electivity are reducing. Overall, while surgery still holds the gold standard,
      medical therapy has a significant role in the treatment of benign prostatic
      hypertrophy. Cost analysis may be a factor in deciding which treatment to have.

PMID- 9158257
TI  - Logistics of performing an ophthalmic assessment in elderly inpatients.
AB  - To assess the feasibility of performing an ophthalmic assessment on elderly
      inpatients, we examined 48 patients over 75 years of age who were consecutively
      admitted to an acute elderly-care ward. Difficulties were encountered in 35
      patients (73%). By employing simple methods to overcome these problems, useful
      information was obtained in all cases and the time taken to complete the
      examination ranged from six to 20 minutes (mean 7.5 minutes). Doctors looking
      after elderly patients should be encouraged to assess visual function and must
      not be deterred by anticipated logistical difficulties.

PMID- 9158258
TI  - An incidental finding of Gitelman's syndrome.
AB  - Gitelman's syndrome is characterised by hypokalaemia, hypomagnesaemia and tetany.
      This rare disorder is not well described in the literature, probably due to its
      similarity with Bartter's syndrome. We describe the symptoms and treatment of a
      young patient whom we consider to have Gitelman's syndrome.

PMID- 9158259
TI  - Inflammatory fibroid polyp of proximal ileum causing recurrent intussusception.
AB  - A 64-year-old female presented with episodes of small bowel obstruction.
      Ultrasound and barium meal showed a polypoidal lesion in the proximal segment of
      small bowel. The patient underwent emergency surgery because of signs of
      impending acute intestinal obstruction. Pathology showed characteristics features
      of an inflammatory fibroid polyp (IFP) which is an important though rare benign
      cause of small bowel obstruction. We document clinical and pathological aspects
      of this case.

PMID- 9158260
TI  - A case of congenital penile sinus.

PMID- 9158261
TI  - Statins and coronary artery disease--it's the clinical endpoints that count.

PMID- 9158262
TI  - The corrupting of the medical profession.

PMID- 9158263
TI  - Assessment of thyroid nodules by technetium-99m-tetrofosmin scintigraphy.
AB  - Thyroid nodularity is a common finding. The incidence of thyroid cancer in the
      general population is estimated at 0.1%. Thyroid nodules are evaluated by
      palpation, ultrasonography, radionuclide scintigraphy and fine-needle aspiration
      cytology. Routine thyroid scintigraphy is made by using Tc-99m-pertechnetate or
      the I-131 and I-123 scintigraphic method. Tc-99m-tetrofosmin accumulates in the
      myocardium, skeletal muscle, liver, spleen breast tissue, kidney and normal and
      pathological thyroid tissue. We investigated 36 patients (28 females and 8 males)
      with solitary and/or multiple thyroid nodules. All the patients were euthyroid,
      and their thyroid nodules were diagnosed by palpation and ultrasound examination.
      Thyroid scintigraphy was applied by Tc-99m-pertechnetate, then thyroid fine
      needle aspiration biopsy was performed. Finally, Tc-99m-tetrofosmin scintigraphy
      was carried out. Five patients (14.8%) had differential thyroid carcinoma, 23
      (63.8%) had thyroid adenoma, 1 (0.02%) had Riedel's thyroiditis and 7 (19.4%) had
      follicular cyst. We detected 80% uptake in the early phase and 100% in the late
      phase by Tc-99m-tetrofosmin scintigraphy in the differentiated thyroid carcinoma
      group. In summary, we claim that Tc-99m-tetrofosmin may be an important
      scintigraphic method to identify thyroid malignancy from benign thyroid
      pathologies.

PMID- 9158264
TI  - A clinical comparison of typhoid fever caused by susceptible and multidrug
      resistant strains of Salmonella typhi.
AB  - The clinical features and response to therapy with ciprofloxacin were studied in
      two groups of patients: those infected by susceptible strains of Salmonella typhi
      and others infected by multidrug-resistant strains. There was no significant
      difference in the clinical presentation, laboratory findings and outcome between
      the two groups. Patients infected with multidrug-resistant strains, however,
      defervesced in significantly longer time (5.5 days) than those infected by
      susceptible strains (4.35 days) (p = 0.031). In areas with high prevalence of
      multidrug-resistant Salmonella infection, empiric treatment with quinolones or
      third-generation cephalosporins of all patients with suspected typhoid fever
      until the results of culture sensitivity tests are available may lead to better
      outcome.

PMID- 9158265
TI  - Equivalence of asthma control with new CFC-free formulation HFA-134a
      beclomethasone dipropionate and CFC-beclomethasone dipropionate.
AB  - The study was designed to test for equivalence of asthma control between a new
      aerosol formulation of beclomethasone dipropionate (BDP) incorporating a
      chlorofluorocarbon-(CFC) free, hydrofluoroalkane propellant (HFA-134a) and the
      conventional beclomethasone aerosol formulated in CFC propellants. Sixty-eight
      asthmatic patients entered an eight-week, randomised, double-blind crossover
      study. All patients, previously stabilised on BDP, were randomised to receive the
      same dose of BDP from each of the study treatments. Statistically significant
      equivalence was demonstrated between HFA-BDP and CFC-BDP for asthma control
      parameters: FEV1, morning and evening PEF, sleep disturbance, wheeze and cough,
      morning breathlessness and bronchodilator use. Such equivalence was also
      demonstrated for safety parameters. To conclude, it has been demonstrated that
      HFA-BDP achieves a level of asthma control that is clinically and statistically
      equivalent to CFC-BDP in terms of efficacy and safety, at total daily doses
      ranging from 200 micrograms to 600 micrograms in asthma patients previously
      stabilised on inhaled CFC-BDP.

PMID- 9158266
TI  - Comparative effects of calcipotriol ointment (50 micrograms/g) and 5% coal tar/2%
      allantoin/0.5% hydrocortisone cream in treating plaque psoriasis.
AB  - The comparative efficacy, tolerability and acceptability of calcipotriol ointment
      (50 micrograms/g) and 5% coal tar/2% allantoin/0.5% hydrocortisone cream were
      determined in 122 patients with chronic plaque psoriasis affecting at least 100
      cm2 of skin. Both preparations were applied twice daily for up to 8 weeks. At the
      end of treatment, investigators considered calcipotriol significantly more
      effective in the proportion of patients 'cleared' or 'markedly improved'
      (calcipotriol 72.3%, coal tar/allantoin/hydrocortisone 49.1%: p < 0.02).
      Calcipotriol was also superior in reducing the total sign score (p = 0.002), and
      individual scores for scaliness (p < 0.0001) and thickness (p = 0.001). The
      proportion of patients with less than 100 cm2 of affected skin at the end of
      treatment was significantly greater in the calcipotriol group (p < 0.05).
      Patients considered calcipotriol significantly more effective overall (p < 0.02)
      and in reducing flakiness/scaliness of skin (p = 0.001). Adverse events, most of
      which were application related and mild to moderate, were recorded in 15 (23.1%)
      patients using calcipotriol and in 10 (17.5%) patients using coal
      tar/allantoin/hydrocortisone (n.s.), and contributed to treatment withdrawal in
      one (1.5%) and three (5.3%) patients, respectively.

PMID- 9158267
TI  - A randomised study to compare the efficacy and safety of new 17 beta-oestradiol
      transdermal matrix patch with Estraderm TTS 50 in hysterectomised postmenopausal
      women. The Lyrelle Study Group.
AB  - This study was designed to compare the efficacy and safety of two sizes of
      Lyrelle, a new matrix design transdermal oestrogen patch, with Estraderm TTS 50,
      a reservoir system. Three hundred and ninety-four (394) hysterectomised
      postmenopausal women between 30 and 65 years of age participated in this open
      label, randomised, multicentre clinical trial. The main efficacy criterion was
      the reduction in the mean number of hot flushes per day at six months. Secondary
      efficacy end points included other climacteric symptoms as well as various
      psychofunctional and genitourinary disorders. A significant decrease from
      baseline in the mean number of hot flushes/day was observed in all three groups
      from the end of cycle 1, reaching 90% at the end of cycle 7. there was no
      statistically significant difference between Lyrelle 50 and Estraderm at any time
      point for any parameter; however, between-group differences between Lyrelle 80
      and Estraderm for various parameters were seen in the first three cycles in
      favour of Lyrelle 80. A similar impact on blood lipid levels was observed in all
      three groups, without significant between-group differences. We conclude that the
      new Lyrelle patch is a highly effective system for transdermal oestrogen
      replacement therapy that may enhance long-term patient compliance.

PMID- 9158268
TI  - Desmopressin and imipramine in the management of nocturnal enuresis: a
      multicentre study.
AB  - The efficacy and safety of desmopressin (Minirin/DDAVP) treatment compared with
      imipramine were investigated in a multicentre, open, cross-over design in 57
      patients, aged 6-15 years, affected by nocturnal enuresis to establish the best
      therapeutic approach to this condition. After a two-weeks observation and control
      period, patients were randomised to one of two groups: intranasal administration
      of desmopressin, 30 micrograms/day for three weeks, followed by imipramine, 0.9
      mg/kg for a further three weeks, or imipramine 0.9 mg/kg for three weeks,
      followed by desmopressin, 30 micrograms/day for a further three weeks. Following
      treatment, all patients were observed for a further two weeks. Administration of
      either treatment protocol resulted in a statistically significant decline in the
      number of enuretic episodes per week compared to the control. The greater
      antidiuretic effect observed in the group receiving imipramine followed by
      desmopressin suggests the two compounds have different profiles. Also, when the
      treatment period was compared with the follow-up, the antidiuretic effect had a
      longer duration in the group initially given imipramine. No further improvement
      was seen when desmopressin was administered first, with a mild worsening of the
      effect sometimes occurring, suggesting a different carry-over effect between the
      two treatments. This suggests that desmopressin offers a better approach to the
      management of nocturnal enuresis.

PMID- 9158270
TI  - The cult of the double-blind placebo-controlled trial.
AB  - The double-blind, placebo-controlled trial is held as the gold standard in
      medical knowledge, but this tool of investigation has its weaknesses. These
      include ethical limitations on the types of comparison that can be undertaken,
      the central conflict between best practice for an individual and trial protocols,
      problems of applicability to the general population and applicability of work
      done on one population to another, type II errors, publication bias, misuse and
      limitation of statistics, fraud, maintenance of blinding, asking the wrong
      question, and a simplistic, reductionist view of clinical management. The
      concentration on the randomised, controlled trial devalues information from other
      sources, such as natural history studies, clinical experience and case reports.
      The randomised, controlled trial is an important source of information and as
      physicians we should welcome more well-crafted trials, but they are not the only
      source of information.

PMID- 9158269
TI  - Efficacy and safety of promethazine hydrochloride as a local anaesthetic agent
      for inguinal hernia repair: a pilot study.
AB  - Promethazine hydrochloride is known to possess properties as a local anaesthetic
      which scientists have not researched well. Therefore, a prospective, randomised,
      double-blind clinical study was conducted to evaluate the efficacy of
      promethazine hydrochloride compared to lignocaine hydrochloride, when used as a
      local anaesthetic agent. Twenty adult male patients undergoing inguinal hernia
      repair were included in the study. Regional nerve block technique was employed in
      all the patients. Efficacy of the agents was assessed on a four-point scale and
      by recording the pulse and the blood pressure. Promethazine hydrochloride was
      found to be as effective as lignocaine hydrochloride in terms of the intensity
      and the duration of regional anaesthesia produced. None of the patients from
      either group required additional anaesthesia in any form, and no complications
      were witnessed. To conclude, promethazine hydrochloride appears to be a safe
      alternative to lignocaine hydrochloride for performing surgery under regional
      anaesthesia.

PMID- 9158272
TI  - Hickman lines inserted and managed by a general surgical team: longevity and
      complications.
AB  - Long-term venous access lines are commonplace in the management of patients
      requiring continuous intravenous chemotherapy, intravenous nutrition or simply as
      a means of avoiding repeated peripheral access lines in patients with difficult
      venous access. The insertion and maintenance of these lines is not without major
      complication. Four years' experience with the Hickman catheter in a general
      surgical oncology setting are reviewed. Thirty-seven lines were inserted in 37
      patients with a mean longevity of 107 days (range 2-322) and an overall
      complication rate of 1.25 per 1000 catheter days. Four catheters were removed
      prematurely due to late complications. These figures compare favourably with
      results for long-term venous access from larger specialist units.

PMID- 9158271
TI  - Stress echocardiography.
AB  - Stress echocardiography has a number of advantages over exercise
      electrocardiography. It has superior sensitivity and specificity as it detects
      wall motion abnormalities, an earlier and more specific marker for myocardial
      ischaemia than ST segment depression. It can also localise ischaemia and identify
      hibernating myocardium. Compared with radionuclide imaging, stress
      echocardiography has similar accuracy but is cheaper and does not involve
      exposure to ionising radiation. The disadvantage of stress echocardiograph is
      that it requires expertise and specialist experience of at least 100 studies.
      Current research aims at improving objective methods of analysing results. The
      technique is justifiably being adopted throughout the UK.

PMID- 9158273
TI  - Frusemide-induced bullous pemphigoid.
AB  - Bullous pemphigoid is a rare complication of frusemide therapy. We present two
      patients in whom the link between frusemide and this condition was not recognised
      early, and continued frusemide therapy resulted in prolonged leg blistering and
      ulceration. On withdrawing the drug, all lesions in both patients resolved
      completely. Although uncommon, this frusemide reaction needs to be borne in mind
      as it can add to the morbidity of elderly patients with heart failure.

PMID- 9158274
TI  - Vitamin B6 responsive sideroblastic anaemia in a patient with tuberculosis.
AB  - A 39-year-old woman was admitted with fatigue, weight loss, and fever. Nothing,
      except skin pallor could be found on physical examination. Her haemoglobin (Hb)
      was 6.3 g/dl. The blood picture showed dimorphic red cell changes and there were
      dyserythropoiesis and ring sideroblasts in the bone marrow. After detailed
      investigations, she was diagnosed with tuberculosis, and anaemia was assigned to
      chronic disease. With anti-tuberculosis therapy (including isoniazid), her Hb and
      bone marrow findings returned to normal. After cessation of therapy, Hb fell to
      8.9 g/dl. Bone marrow examination again showed dyserythropoietic morphologic
      abnormalities and ring sideroblasts. No reason could be identified to explain the
      recurrence of anaemia. When we realised that preparations of isoniazid included
      vitamin B6 to prevent the development of sideroblastic anaemia, we challenged
      with pyridoxin 200 mg daily. Her Hb rose to 14.6 g/dl. We suggest that in any
      cases with sideroblastic anaemia, if no cause can be identified, or anaemia
      persists or recurs despite therapy, pyridoxine therapy should be instituted.

PMID- 9158275
TI  - Inhaled nitric oxide for right ventricular dysfunction following cardiac
      transplantation.
AB  - A 55-year-old man developed postoperative hypotension following orthotopic
      cardiac transplantation, unresponsive to support with inotropes and
      counterpulsation. Acute right ventricular failure was confirmed by
      transoesophageal echocardiography, and the introduction of inhaled nitric oxide
      resulted in immediate improvement. A beneficial effect persisted for 11 days,
      with hospital discharge two months postoperatively.

PMID- 9158276
TI  - Bilateral tubal ectopic pregnancy: diagnostic pitfalls.
AB  - A rare case of simultaneous bilateral tubal pregnancy after natural conception is
      presented, together with a review of the literature on this topic. Diagnostic
      aspects and treatment options are discussed.

PMID- 9158277
TI  - Bilateral ureteric obstruction secondary to the prolonged use of tiaprofenic
      acid.
AB  - There is increasing awareness that the long-term use of the non-steroidal anti
      inflammatory agent tiaprofenic acid (Surgam) is associated with a severe form of
      cystitis. The condition is usually reversible with complete resolution of
      symptoms on stopping the drug. We present a case of tiaprofenic acid-induced
      cystitis resulting in bilateral hydronephrosis suggesting ureteric obstruction.
      The previous reported cases are reviewed and the risks of delay in withdrawal of
      the drug and of permanent ureteric damage are discussed.

PMID- 9158278
TI  - Laryngeal tuberculosis: an unsuspected danger.
AB  - It is always important to treat conditions which may be cancerous with respect
      and, where there is suspicion, to take biopsies for histological examination. A
      hoarse voice may, in addition, be a sign of tuberculosis of the larynx, and the
      clinical appearance can be similar to a carcinoma. Preoperative chest x-ray (not
      always performed) and an awareness by the histologist of such a possibility are
      important now that this condition is increasing in frequency in parallel with
      conditions where immunological status is compromised.

PMID- 9158279
TI  - Please write out the acronyms every time.

PMID- 9158280
TI  - Early life and adult disorder: research themes.

PMID- 9158281
TI  - Infections in childhood and pregnancy as a cause of adult disease--methods and
      examples.
AB  - Infection in childhood can occur in utero, perinatally or in postnatal life.
      Infections at these ages can have profound effects on anatomical structure and on
      developmental processes of a number of systems. These effects may lead to adult
      disease directly or increase the susceptibility to factors later in life. The
      detection of such childhood infections may be difficult once adult disease has
      developed. In this chapter we described the type of epidemiological evidence that
      might suggest such a situation and give examples of infections known to cause
      adult disease which illustrate these patterns.

PMID- 9158282
TI  - Infection in childhood and neurological diseases in adult life.
AB  - Other chapters in this issue discuss the evidence that implicates infection
      during infancy and childhood in the etiology of respiratory disease. Here I argue
      that experience of infection in early life may also be involved in the aetiology
      of some diseases of the adult nervous system. The descriptive epidemiology of
      three neurological diseases is compatible with the hypothesis that they are
      delayed consequences of childhood infection. It is not difficult to imagine that
      the effects of an infection which results in loss of cells from an organ system,
      like the central nervous system, whose cell populations have lost the capacity to
      replace themselves by mitotic division could remain hidden until unmasked by
      ageing. Such a mechanism may be important in the aetiology of motor neuron
      disease and Parkinson's disease. Age-related differences in host response, which
      may be partly related to a maturing immune system, are known to influence both
      short- and long-term outcome for several infections. Perhaps the immune response
      to infection with Epstein-Barr virus, or another common micro-organism with
      similar epidemiology, in adolescence or early adult life is sometimes directed at
      antigens that are also present in the central nervous system. At present, the
      evidence that supports these hypotheses is largely circumstantial. But it may be
      possible to devise ways of testing them both epidemiologically and in the
      laboratory.

PMID- 9158283
TI  - Lung development and early origins of childhood respiratory illness.
AB  - In the last two decades, 5 cohort studies have been initiated to examine the
      association of infant respiratory function with genetic and environmental risk
      factors, as well as with subsequent lower respiratory illness in early childhood.
      While the current complexity of respiratory function tests in this age group
      precludes study samples with sufficient power to examine more complex issues,
      information from these studies has provided an exciting adjunct to that available
      from the longer cohort studies. Premorbid alterations in airway function or lung
      development increase the risk of wheezing lower respiratory illnesses during the
      preschool years and the risk of impaired airway function at 5-6 years of age. In
      addition, gender differences in airway function and the response to maternal
      smoking have been observed. Larger collaborative population-based studies are
      needed to explore the environmental, genetic and immunological mechanisms
      responsible, but will depend on the development of less invasive tests of airway
      function appropriate for use in healthy infants.

PMID- 9158284
TI  - The beginnings of chronic airflow obstruction.
AB  - Recent follow-up studies have provided convincing evidence that the foundations
      of chronic airflow obstruction (CAO) are laid in utero and early childhood. Men
      born in Hertfordshire and Derbyshire, England, were more likely to have impaired
      lung function at 60-70 years of age if they had been lighter at birth and if they
      had had lower respiratory tract infection (LRTI) in the first 2 years of life.
      Furthermore, they were more likely to have died from chronic obstructive
      pulmonary disease if they had been lighter at 1 year of age. These findings
      suggest that impairment of pulmonary growth in utero and early childhood, as a
      consequence of undernutrition and LRTI, plays an important part in the
      development of CAO in late adult life. This may be of particular importance for
      the future respiratory health of developing nations as the additive effects of
      smoking take hold.

PMID- 9158285
TI  - Asthma: early predisposing factors.
AB  - The significance of factors affecting the development of asthma and atopy in
      children must be judged against their ability to contribute to the increase in
      childhood asthma. Although genetic factors are clearly important to the
      development of asthma and atopy, they can not explain the increased prevalence of
      these conditions.

PMID- 9158286
TI  - Effects of the intrauterine environment on childhood growth.
AB  - The intrauterine environment plays a critical role in childhood growth. Infants
      exposed to acute malnutrition in early pregnancy are more likely to be obese in
      later life. Similarly, children exposed to hyperglycemia in utero are also more
      likely to develop insulin intolerance and obesity during childhood. The
      mechanisms underlying these changes are not understood. However, animal
      experiments suggest that severe overnutrition or undernutrition during pregnancy
      may affect hypothalamic development, or pancreatic beta-cell development. The
      effects of cigarette smoking on childhood growth can best be explained by the
      increased risk of intrauterine growth retardation. In contrast, alcohol ingestion
      during pregnancy leads to a syndromic decrease in childhood head circumference,
      stature, and weight. The effects of cocaine are most likely multifactorial, since
      cocaine ingestion tends to covary with tobacco use, alcohol use, opiate use, and
      low socioeconomic status. The most striking effects of the intrauterine
      environment on childhood growth are seen in children with intrauterine growth
      retardation. These children remain significantly lighter and shorter than their
      peers. Efforts to reverse intrauterine growth retardation have been
      disappointing, and at times risky. However, caloric supplementation in
      undernourished populations may be of significant benefit. The use of growth
      hormone promises to reduce some of the height deficits in children with
      intrauterine growth retardation. However, to date there is no evidence suggesting
      changes in final height in children with intrauterine growth retardation who
      receive growth hormone.

PMID- 9158287
TI  - Fetal nutrition and cardiovascular disease in later life.
AB  - Recent finding suggest that many fetuses have to adapt to a limited supply of
      nutrients and in doing so they permanently change their physiology and
      metabolism. These 'programmed' changes may be the origins of a number of diseases
      in life, including coronary heart disease and the related disorders stroke,
      diabetes and hypertension.

PMID- 9158288
TI  - Non-insulin-dependent diabetes mellitus.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) occurs predominantly after the
      age of 50 years but is not easy to distinguish from late onset insulin-dependent
      diabetes. It is likely that misclassification is rare in a Caucasian population.
      Whilst NIDDM is widely believed to be genetically determined, recent
      epidemiological observations have consistently revealed statistical associations
      between indices of poor fetal and infant growth with susceptibility to loss of
      glucose tolerance in adult life. A possible explanation of these observations is
      that environmental constraints on fetal growth lead to permanent changes in
      organogenesis such that a poor capacity of insulin secretion and insulin
      resistance result. It is postulated that these adaptive responses serve to
      preserve the growth of certain organs, such as the brain, at the expense of
      others, such as the viscera. In addition, alterations in the function of organs,
      such as the liver, serve to aid survival of the offspring under conditions of
      poor postnatal nutrition. The results of studies of an animal model in which
      pregnant rats were fed a reduced protein diet are consistent with these concepts.

PMID- 9158289
TI  - Nutrition and cognitive development.

PMID- 9158290
TI  - The early origins of schizophrenia.
AB  - Large population-based studies indicate that children who will as adults develop
      the clinical syndrome of schizophrenia are different from their peers in terms of
      the acquisition of a range of neurological, cognitive and behavioural
      characteristics. These studies are also identifying possible causal factors which
      might operate early in life and so be responsible for a longitudinal aspect of
      the disorder. Studies of the brain yield results consistent with the multi-system
      nature of the clinical syndrome of schizophrenia in adult life, and with the
      notion of a longitudinal or developmental phenotype, of which the adult syndrome
      is but one aspect. Work in these areas is reviewed with special reference to
      national birth cohorts from Britain and Finland.

PMID- 9158291
TI  - Childhood adversities and psychosocial disorders.
AB  - Adverse childhood experiences--especially inadequacies in early parental care-
      are associated with elevated rates of both acute and chronic psychosocial
      disorders in adult life. In most instances, adverse outcomes are confined to a
      minority of children exposed; variations in the severity or pervasiveness of
      early risk, individual differences in susceptibility, and interactions with later
      stressors are all thus likely to be important in mediating effects. At present,
      knowledge of intervening processes is limited, and dependent on retrospective
      studies of adult samples or short-term longitudinal findings in childhood. We
      review current evidence on the long-term outcomes of prenatal divorce, childhood
      maltreatment, and institutional rearing, and on the early antecedents of
      depression and antisocial behaviour in adult life, to highlight possible
      interviewing mechanisms. Most long-term sequelae seem likely to depend on a
      series of shorter-term links, some running through elevated risks of continued
      environmental adversity, others through psychological vulnerabilities and
      problems in social relationships.

PMID- 9158292
TI  - Early determinants of behaviour: evidence from primate studies.
AB  - The idea that early experiences disproportionately influence adult behaviour has
      long been a fixture of mainstream developmental theory. Although unambiguous
      empirical support for this view at the human level is surprisingly sparse,
      compelling evidence from animal studies abounds. Recent studies with rhesus
      monkeys have demonstrated dramatic short- and long-term effects of differential
      early social experiences on both behavioural and physiological functioning. Early
      social relationships with mothers or other caregivers appear to provide
      especially powerful determinants of behavioural propensities throughout the
      lifespan.

PMID- 9158293
TI  - Critical periods in childhood learning.
AB  - The human body is born with 'hard wiring' that leads the baby to pay attention to
      certain things in the environment, especially the communications of caregivers.
      These inborn predispositions are gradually shaped by the environment of the
      family, a 'curriculum for babies' which is rich on communication and making sense
      of the world. Day care and nursery education can complement and enhance the
      child's learning, especially if they are of high quality. Research has shown
      again and again that early learning has lasting effects on development although
      they are rarely irreversible.

PMID- 9158294
TI  - Changing social factors and their long-term implications for health.
AB  - This paper presents findings and arguments to show the power of social factors to
      affect health at the individual and at the national level. Social factors most
      strongly and negatively associated with health, at both levels, are those that
      indicate disorganisation and disruption, perceived helplessness and lack of
      support, low educational attainment, and poverty. Adverse changes in these social
      factors and their negative effects on health have been observed in many studies.
      When such adverse changes affect the lives and health of children, and those who
      will become parents, they affect the present and long-term future health of
      individuals because of the processes of biological programming described in this
      and other papers presented here. Such adverse changes in social factors also
      adversely affect the social circumstances of childhood, which in turn have a
      negative impact on health. Because changing social factors affect biological
      programming and social capitalisation, awareness of the health damaging effects
      of recent social change provides information on the future health of the
      population.

PMID- 9158295
TI  - Social and biological pathways linking early life and adult disease.
AB  - Evidence is presented for a pathways model linking early life factors and adult
      disease, which takes account of the inter-relationships between social and
      biological risks throughout the lifecourse. Few studies, if any, have yet
      recorded adequate birth to death information which could be used to quantify the
      effects of different factors and their timing. Hence, there is only limited
      understanding of the extent to which biological and social risks experienced at
      different life stages combine to influence adult disease. However, some of the
      pathways between early and later life are suggested when evidence from earlier
      stages of the lifecourse is linked to that from studies at older ages, in which
      adult disease risk factors have been established. Further support for pathway
      effects is provided by studies showing that health outcomes of early biological
      insults can depend on the subsequent social and biological environment. Thus, it
      is argued that adult disease will be more fully understood when account is taken
      of the combined effects of social and biological risk occurring at different life
      stages.

PMID- 9158296
TI  - Importance of the transitional zone between the cervical stroma and the
      parametrium in the treatment of cervical carcinoma.
AB  - OBJECTIVES: Parametrial invasion is an important risk factor in cervical
      carcinoma. Because the vessels of the parametrium start in the zone between the
      cervical compact stromal layer and the parametrium, which we have defined as the
      parametrial initial zone (PIZ) or transitional zone, the invasion of a carcinoma
      into this part of the cervix is also important. Our objectives in this study were
      find a characteristic index of the transitional zone and to clarify the
      relationship between a transitional-zone invasion and the prognosis in a case.
      METHODS: Thirty-three cases of carcinoma in situ were available to use for the
      morphological examination of the cervix. The cervix was divided into 8-12
      sections. In each section, the outer diameters of the short axis of the arteries
      were measured with a light microscope and a micrometer. Using the arterial
      diameter as the characteristic index of the transitional zone, we performed
      epidemiological studies on 312 patients with clinical Stage Ib-III squamous-cell
      carcinoma of uterine cervix. RESULTS: The arteries with an axis exceeding 300
      microns were concentrated in the transitional zone at a rate of 94.6%. Therefore,
      arteries of this size are used as the characteristic index of the transitional
      zone. Patients with invasion to transitional zone only had lymph node metastasis
      at the rate of 28.1%, compared with 0% for patients who had no permeation to the
      zone (p < 0.001). The 5-year survival rate of patients with invasion to the
      transitional zone only was 87.3%, which is significantly lower than those without
      invasion (99.2%) (p < 0.01). CONCLUSIONS: Measuring the short axis (300 microns <
      or = ) of the artery is the best method by which to pinpoint the transitional
      zone. The invasion of a carcinoma into the transitional zone in the cervix should
      be treated as a parametrial involvement.

PMID- 9158297
TI  - Effect of population density on the early post-implantation mouse embryo growth
      in vitro.
AB  - OBJECTIVES: To investigate the relationship between embryo population density and
      embryo development in vitro. METHODS: Swiss Webster albino mice were used and
      blastocysts were flushed from the uterine horns. Various numbers of blastocysts
      were randomly assigned to separate 35 mm dishes and cultured for 9 days. RESULTS:
      The effect of duration of culture to the mean success rates was different as the
      number of embryos in the dish was changed. In early egg cylinder (EEC) stage, the
      mean success rate was a flat function of the number of embryos. But the mean
      success rate was a decreasing function in late egg cylinder (LEC) stage and the
      decreasing rate was faster in early somite (ES) stage. Interestingly, the mean
      success rate to ES stage was nearly constant when more than 10 embryos were
      cultured in one dish. CONCLUSION: The success rate to each developmental stage in
      vitro decreased as the number of embryos in the dish and the duration of cultured
      increased.

PMID- 9158298
TI  - Effects of all-trans retinoic acid on choriocarcinoma cells in vitro.
AB  - OBJECTIVES: To determine the activities of all-trans retinoic acid (RA) on
      choriocarcinoma cells in vitro. METHODS: The antiproliferative effect of all
      trans RA on 4 choriocarcinoma cell lines was measured by the MTT assay. The
      effect of all-trans RA combined with methotrexate or actinomycin-D was then
      examined. The effect of all-trans RA on hCG secretion was also studied. The gene
      expression of retinoic acid receptors (RARs) was examined by RT-PCR. RESULTS: All
      trans RA inhibited cell proliferation dose- and time-dependently; a 6-day
      exposure to 1 microM all-trans RA suppressed the cell growth by 67.8%-82.0%
      compared to the controls. An enhanced effect was observed in the combined
      administration of all-trans RA and methotrexate or actinomycin-D. The secretion
      of hCG increased 4-fold to 9-fold by the addition of 1 microM all-trans RA. RARs
      genes were expressed in all cell lines. CONCLUSION: The anticancer activity
      presented here appears to warrant further evaluation of all-trans RA as adjuvant
      therapy for choriocarcinoma.

PMID- 9158299
TI  - Cellular and subcellular localization of nicotinamide adenine dinucleotide
      phosphate diaphorase activity.
AB  - OBJECTIVE: To determine the cellular and subcellular distribution of nicotinamide
      adenine dinucleotide phosphate diaphorase (NADPH-d) in the human placenta and
      thereby to shed light on the possible role of nitric oxide (NO) and NO synthase
      in this tissue. METHODS: NADPH-d activity in 10 term placenta and in 10 first
      trimester placentas was examined by enzyme histochemistry and by both light
      microscopy and electron microscopy. RESULTS: Light microscopy revealed that NADPH
      d activity was marked in the syncytiotrophoblasts, moderate in the endothelium of
      cord vessels, and weak in the amniotic epithelia and chorionic trophoblasts. At
      the electron-microscopic level, NADPH-d activity was apparent as small patches
      distributed throughout the cytoplasm of the syncytiotrophoblasts. CONCLUSION: NO
      might be generated in the syncytiotrophoblast of the human placenta and might
      play a role in the regulation of placental hemodynamics or in the signaling
      between the syncytium and the villous mesenchyme.

PMID- 9158300
TI  - Immunohistochemical studies on matrix metalloproteinase-9 (MMP-9) and type-IV
      collagen in endometrial carcinoma.
AB  - Immunohistochemical staining of MMP-9 and the type-IV collagen was performed on
      paraffin sections of endometrial carcinoma. Immunostaining in 129 cases of
      endometrial cancer detected MMP-9 in 19.0% of the cases. MMP-9 positive was shown
      in 30% of the cases with vessel invasion, and in 12.7% of the cases without
      vessel invasion (p < 0.05). MMP-9 showed positive in many cases with poor
      differentiation and lymph node metastasis, but still failed to achieve
      statistical significance. MMP-9 staining did not correlate with disease outcomes.
      We can not clarify that MMP-9 is associated with tumor-cell invasion and
      metastasis. Type-IV collagen deposition at the tumor-stromal border was studied
      in 58 cases of endometrial carcinoma in which disruptions were seen in varying
      degrees. The type-IV collagen in the primary lesion decreased as the
      differentiation decreased. Even in the lymph node metastasis lesions, the type-IV
      collagen was stained and was almost in agreement with the primary lesions. In the
      primary lesions, there was no relationship between MMP-9 staining and the type-IV
      collagen. It was suggested that the type-IV collagen observed in endometrial
      carcinoma was more concerned with the differentiation of the tumor than with the
      degradation by MMP-9.

PMID- 9158301
TI  - Acute myocarditis with eosinophilia presenting as asymmetric septal hypertrophy
      during pregnancy.
AB  - A pregnant female at 24 weeks' gestation developed acute myocarditis with
      eosinophilia presenting as asymmetric septal hypertrophy. Her clinical course
      improved with ordinary treatment within a few weeks.

PMID- 9158302
TI  - The detection of right-sided congenital diaphragmatic hernia in monozygotic twins
      on prenatal ultrasonography.
AB  - The diagnosis of a pair of monozygotic twins with right-sided diaphragmatic
      hernia under ultrasound is described. Aspects of heredity, diagnosis and
      management are discussed.

PMID- 9158303
TI  - Effects of hormone replacement therapy on sexuality in postmenopausal women in a
      mideast country.
AB  - OBJECTIVE: During the postmenopausal period, sexual interest and activity seem to
      decline, as part of the menopausal effect of oestrogen deficiency. The aim of
      this study was to evaluate other factors that could contribute to sexual
      dysfunction and the effect of hormone replacement therapy among postmenopausal
      women in Kuwait. METHOD: Between June 1992, and June 1994, details of sexual
      history were compiled from 261 postmenopausal women that attended the Menopause
      Clinic at the Maternity Hospital, Kuwait. The effect of hormone replacement was
      analysed from the sexual history and the bacteriology of the lower genital tract.
      RESULTS: About 71% of the 261 postmenopausal women were still sexually active.
      Among those not sexually active, 38% had loss of interest, 22% because of divorce
      or death of husband, 20% from loss of interest by husband, and in 13% because the
      husbands had impotence from medical problems. Of the sexually active women, 41.1%
      had reduced libido. Contributing factors included vaginal symptoms like
      dyspareunia and vaginal dryness, vaginal infection, disturbances in the
      premenopausal menstrual pattern and disharmony with husbands. About 23 to 45% of
      the postmenopausal women with oestrogen replacement therapy, had significant
      relief of their symptoms of sexual dysfunction. Vasomotor symptoms had better
      response compared to sexual dysfunction (p < 0.01). Natural oestrogen gave
      slightly better relief of symptoms of sexual dysfunction than other forms of
      oestrogen therapy. Livial gave complete relief of dyspareunia and vaginal dryness
      in 9.1% and 3.9% respectively, but none of those with libido and vaginal
      discharge had any relief. CONCLUSION: There is a decline in sexual response and
      activity in postmenopausal women in Kuwait. This is however, multifactorial in
      origin. Although oestrogen replacement therapy gives significant relief in
      symptoms of sexual dysfunction, other contributory factors should always be
      evaluated.

PMID- 9158304
TI  - Effect of oocyte retrieval from a small leading follicle in fixed-schedule in
      vitro fertilization program.
AB  - OBJECTIVE: To evaluate the propriety of oocyte retrieval (OR) form a small
      leading follicle during a fixed-schedule in vitro fertilization (IVF) program.
      METHODS: OR was fixed only to take place on Wednesdays. Gonadotropin-releasing
      hormone agonist treatment was initiated on the first day of the cycle, human
      menopausal gonadotrophin was given for 7 days starting on the next Monday, and
      human chorionic gonadotrophin (hCG) was given on the Tuesday before the OR.
      Patients were divided into 2 groups according to the follicular size observed
      before the day of hCG administration: Group 1 (141 cycles), with follicles > 16
      mm in mean diameter; and Group 2 (38 cycles) with follicles of 10 to 16 mm in
      mean diameter. RESULTS: Fertilization rates and the incidence of mature oocytes
      were higher in Group 1 than in Group 2. However, the mean number of oocytes
      recovered and pregnancy rates were similar in the 2 groups. CONCLUSION: It is
      worthwhile to retrieve the oocyte from a small leading follicle in a fixed
      schedule IVF program.

PMID- 9158305
TI  - Preinduction cervical ripening: prostaglandin E2 gel vs hygroscopic mechanical
      dilator.
AB  - OBJECTIVES: To evaluate the efficacy and safety of hygroscopic mechanical
      dilators (Dilapan) for ripening the pregnant cervix prior to induction of labour
      at or near term and to compare it with an intracervical PGE2 gel (Prepidil).
      METHODS: One hundred and eighty-five women (69 nulliparae, 116 multiparae) at
      term with singleton pregnancies in cephalic presentation, who were scheduled for
      induction of labour in the labour ward at the National University Hospital, but
      had an unfavourable cervical score were randomized into 2 groups by random number
      table. In group 1 (Prepidil), 0.5 mg of PGE2 in 2.5 ml of triacetin gel was
      inserted into the endocervical canal. In women in group 2 (Dilapan) upto a
      maximum of 4 hygroscopic dilators were placed in the endocervical canal. If
      labour did not ensue at the end of 12 hours of ripening, the cervical score was
      assessed, amniotomy was performed and oxytocin commenced. Neonatal and obstetric
      outcome was compared, statistical analysis performed using Chi-square, and t
      tests. RESULTS: Significantly more women in the group who received Dilapan for
      cervical ripening required amniotomy and oxytocin for induction of labour > 12
      hours after priming compared with the group who received Prepidil (p < 0.001).
      Operative delivery for no progress and fetal distress respectively was similar in
      the 2 groups. The number of cases of hyperstimulation were higher in the Prepidil
      group but did not result in an increased incidence of operative deliveries for
      fetal distress. There was one neonatal death and one case of neonatal sepsis in
      the Dilapan group. Uterine rupture occurred in 1 woman who received Prepidil.
      CONCLUSION: Dilapan, a mechanical method of cervical ripening is as effective as
      the more widely accepted mode of ripening with an endocervical PGE2 gel in
      achieving vaginal delivery. Dilapan would be useful for cervical priming prior to
      induction of labour in places where prostaglandins are not available because of
      cost and the need for a cold chain.

PMID- 9158306
TI  - Risk factors predictive of para-aortic lymph node metastasis in endometrial
      carcinomas.
AB  - OBJECTIVE: To identify risk factors predictive of para-aortic lymph node (PAN)
      metastasis in endometrial carcinomas. METHODS: Sixty patients with endometrial
      carcinomas Stage I to III (FIGO, 1988) who each underwent a complete pelvic and
      para-aortic lymphadenectomy with a semiradical or radical hysterectomy, bilateral
      salpingo-oophorectomy, between April 1988 and March 1996, were included in this
      study. The relationship between PAN metastasis and clinico-pathological factors
      such as histological type, grade, depth of myometrial invasion (MI), vascular
      space involvement (VSI), cervical invasion (CI), peritoneal cytology, tumor size,
      pelvic lymph node (PLN) metastasis, and glutathione S-transferase pi (GST-pi)
      expression was examined using univariate and multivariate analysis. RESULTS:
      Seven variables--G3 grade, more than one-half MI, positive VSI, positive CI,
      tumor size of more than 2 cm in diameter, positive PLN metastasis, and positive
      GST-pi--were significantly correlated with PAN metastasis using univariate
      analysis. Multivariate analysis revealed that of the above 7 variables, 3 were
      significantly and independently correlated with PAN metastasis: more than one
      half MI, positive PLN, and positive GST-pi. The relative risk of a patient with
      these 3 factors having PAN metastasis was 18.0 times greater than the risk for a
      patient without them. CONCLUSION: These variables--More than one-half MI,
      positive PLN, and positive GST-pi--were significantly related to PAN metastasis.

PMID- 9158307
TI  - A case of uterine choriocarcinoma with spontaneous rupture twenty-three years
      following the antecedent pregnancy.
AB  - A 53-year-old woman went into shock with a spontaneous uterine rupture due to
      choriocarcinoma that occurred 23 years after an elective abortion in the first
      trimester, and she underwent an emergency hysterectomy. After 4 courses of
      uneventful postoperative chemotherapy, she suffered from severe pneumonia.
      Fortunately, however, she recovered and has remained in complete remission at 2.5
      years follow-up. This is a case of uterine choriocarcinoma with a spontaneous
      rupture after the longest latent period yet reported.

PMID- 9158308
TI  - The effect of prolonged cycles of chemotherapy on quality of life in gynaecologic
      cancer patients.
AB  - OBJECTIVE: The aim of this study was to determine if the prescription of
      prolonged cycles of chemotherapy to patients with a variety of gynaecologic
      cancers has an adverse effect on quality of life (QOL). METHODS: Patients
      attending a single gynaecologic oncology clinic who received greater than 6
      cycles of chemotherapy were identified. Prior to each chemotherapy cycle,
      patients were asked to complete a modified Functional Assessment Cancer Therapy
      General (FACT-G) quality of life form. QOL scores were compared to their baseline
      or pretreatment score (cycle 1 score), as well as to their score representing the
      completion of primary therapy (cycle 6 score). RESULTS: Seventeen patients were
      identified as having received greater than 6 cycles of systemic cytotoxic
      chemotherapy. The total number of chemotherapy cycles analyzed was 95. Comparing
      QOL scores for cycle 1 and 6 to cycles 7-16, we found no significant alteration
      (improvement or deterioration) in the following subscale scores: physical well
      being (PWB), social well being (SWB), and functional well being (FWB). Similarly,
      overall QOL as represented by the summed individual scores was also not affected
      by the prescription of up to 16 cycles of chemotherapy. Analysis of the emotional
      well being (EWB) subscale scores revealed a significant downward trend after the
      12th cycle of therapy as compared to the 6th cycle (p = 0.04), however this trend
      was not significant when compared to the pretreatment or cycle 1 scores (p =
      0.16). There was however a statistically significant progressive deterioration in
      the subscale score of the relationship with the doctor (RWD). This was most
      marked after the 10th cycle of therapy (p < 0.0001). When split by disease
      status, we again found no statistically significant alteration in PWB, SWB, RWD,
      EWB, FWB and overall QOL for cycle 1 and 6 as compared to cycles 7-17. However,
      those patients who were able to attain a complete clinical response (CCR) disease
      status, achieved a higher SWB (p = 0.003), RWD (p = 0.02), EWB (p = 0.03), and
      overall QOL scores (p = 0.04) while their PWB scores were not statistically
      different from patients with stable (p = 0.7) or progressive disease (p = 0.6).
      CONCLUSION: In conclusion, the prescription of prolonged cycles of chemotherapy
      to patients with gynaecologic cancers does not result in an overall deterioration
      of QOL. Further more an improvement in subscale and overall QOL was demonstrated
      in those patients able to attain a complete clinical response (CCR).

PMID- 9158309
TI  - Thromboembolism treated with low molecular weight heparin in a pregnancy
      complicated by major placenta praevia: a case report.
AB  - The concurrent problems of bleeding placenta praevia and thromboembolism present
      a difficult management problem. We present a case of pulmonary embolism
      successfully treated with low molecular weight heparin in a woman with a major
      grade placenta praevia, who required emergency operative delivery.

PMID- 9158310
TI  - Pheochromocytoma during pregnancy: case report.
AB  - Pheochromocytoma during pregnancy is rare. Only a few hundred cases have been
      published in the literature. We report patients with pheochromocytoma diagnosed
      at antepartum period. Manifestation include hypertension with various clinical
      presentation, possibly resembling those of pregnancy-induced hypertension.
      Confirmation necessitates special biochemical examination and the use of
      different radiological imaging tool. Treatment combines medical procedures with
      surgical exploration, mandating a team approach of diverse medical expertise. In
      the first and second trimesters, tumor resection has a good fetal outcome; in
      later pregnancy, delivery by elective cesarean section followed by tumor
      resection is recommended. The overall prognosis is mainly affected early
      diagnosis and multidisciplinarian management.

PMID- 9158311
TI  - Elevated serum levels of the c-erbB-2 encoded oncoprotein fragment in cases of
      pure preeclampsia and HELLP syndrome.
AB  - OBJECTIVE: During normal human ontogenesis an overexpression of the c-erbB-2
      encoded oncoprotein p185 (HER2/neu) occurs in the placenta and on fetal
      epithelial cells. It is accompanied by the increase of a 105 kD fragment (p105)
      in both maternal serum and cord blood. We examined whether p105 levels in
      maternal serum are influenced by destructions of placental tissue, fetal growth
      disturbances and placental circulation disorders. METHODS: We analysed p105 serum
      concentrations in patients with abortion (n = 25), ectopic pregnancy (n = 5),
      intrauterine growth retardation (n = 9), pregnancy induced hypertension (n = 24)
      and compared them with normal pregnancies of a corresponding gestational age.
      RESULTS: Patients with abortions showed normal p105 values. Intrauterine growth
      retardation was associated with lower p105 levels (p < 0.05) whereas patients
      with pure preeclampsia (p < 0.001) and HELLP syndrome (p < 0.05) had
      significantly higher levels. CONCLUSION: The elevation of p105 in sera of
      preeclamptic women could be due to an increased fetomaternal transfer of p105.

PMID- 9158312
TI  - Vaginal delivery in the grand multipara following previous lower segment cesarian
      section.
AB  - OBJECTIVE: To examine the effect of attempting vaginal birth after cesarian
      section in the grand multipara with one previous cesarian section scar in the
      uterus. METHOD: Over 5-year period (1990-1994) mothers with 6 or more previous
      deliveries and with a previous section scar in the uterus were identified. The
      outcome in these patients who attempted vaginal birth was reviewed. RESULTS: Of
      the 85 patients with the combination of both grand multiparity and a previous
      cesarian section scar in the uterus, 45 attempted a trial of labor. Twenty-seven
      patients (60%) achieved successful uncomplicated vaginal delivery. There was a
      relatively high incidence of serious complications. CONCLUSION: Vaginal birth
      after cesarian section can be achieved in some grand multiparas with a previous
      scar in the uterus. There is an increased risk of serious complications. The
      labor should be very closely supervised and early intervention arranged if there
      is not smooth rapid progress.

PMID- 9158313
TI  - Shortening of the first metatarsal following closing base wedge osteotomy.
AB  - Shortening of the first metatarsal has been one of the reported complications
      noted in association with base osteotomies. Previous studies have used
      radiographs as a means of assessing metatarsal length, the reliability of which
      has been subject to question. In this study, the authors have determined the
      amount of shortening that may be anticipated with a closing base wedge osteotomy
      of the first metatarsal through an experimental model. A mathematical model was
      also devised that confirmed these findings. Additional studies were performed to
      determine what influences other variables may have on this procedure.

PMID- 9158314
TI  - Guillain-Barre syndrome. Review and presentation of a case with pedal
      manifestations.
AB  - Guillan-Barre syndrome is an acute, symmetrical polyneuropathy with distinctive
      features. The early clinical course involves painful paresthesia that is usually
      followed by proximal motor weakness. Albuminocytologic dissociation in the
      cerebrospinal fluid is considered diagnostically important. Therapy ranges from
      supportive measures including physical therapy to surgical intervention for
      residual deformities. A case with pedal manifestations is presented.

PMID- 9158315
TI  - Buffered lidocaine decreases the pain of digital anesthesia in the foot.
AB  - The pain associated with injections for inducing digital anesthesia can be
      decreased by adding sodium bicarbonate to plain lidocaine. A randomized, double
      blind study has demonstrated that 24 out of 30 participants indicated on a visual
      analogue scale that buffered lidocaine is less painful than plain lidocaine. The
      pain decreased by 50% or more for almost half of the participants. Practitioners
      can easily buffer lidocaine in the office by adding a small volume of sodium
      bicarbonate to plain lidocaine.

PMID- 9158316
TI  - Deep venous thrombosis. The dilemma of diagnosis.
AB  - Despite advanced medical technology, deep venous thrombosis continues to be a
      seriously underdiagnosed common postsurgical complication of the patient,
      particularly of lower extremity procedures, often requiring postoperative bed
      rest as in any routine podiatric surgery. Deep venous thrombosis and its
      complication, pulmonary embolism, are elusive clinical conditions since patients
      often tend to exhibit neither specific nor reliable signs or symptoms. However,
      the suspicion of the surgeon, generally based on subtle clinical manifestations,
      is the most important step in the diagnosis. Diagnosis will never be made unless
      he or she entertains the possibility. Since prevention of the potentially fatal
      outcome of pulmonary emboli secondary to deep venous thrombosis and possibly the
      serious morbidity caused by long-term sequelae in the lower extremity is now
      possible, the importance of an early, adequate diagnosis is indisputable.
      Diagnosis on clinical grounds alone is notoriously unreliable and objective tests
      are necessary to avoid overtreatment or undertreatment.

PMID- 9158317
TI  - Solitary IgA myeloma of the foot. A case report and review of the literature.

PMID- 9158318
TI  - Osteitis fibrosa cystica and chronic renal failure.

PMID- 9158319
TI  - Cutaneous fibrous histiocytoma.

PMID- 9158320
TI  - Bilateral large ankle lipomas.

PMID- 9158321
TI  - Imipenem-cilastatin-induced leukocytoclastic vasculitis.
AB  - A maculopapular rash has been associated with the administration of imipenem
      cilastatin, an antibiotic that was used for treatment of a postoperative
      infection. This is a first-time association of imipenem with a leukocytoclastic
      vasculitic reaction. Leukocytoclastic vasculitis has been previously documented
      with ciprofloxacin, zidovudine, piperazine, and lithium.

PMID- 9158322
TI  - Reappraisal of the negative impression cast and the subtalar joint neutral
      position revisited again.

PMID- 9158323
TI  - Studying expertise in music reading: use of a pattern-matching paradigm.
AB  - Two experiments are described that make use of a pattern-matching paradigm to
      investigate perceptual processing of music notation. In Experiment 1, it is
      reported that the speed of comparing two visually presented musical sequences is
      related to the sight-reading skill of the subjects. The effect of the temporal
      and pitch structure of the comparison stimuli is also assessed. In Experiment 2,
      eye-movement recordings were taken as subjects performed the task. These data
      demonstrated that more experienced musicians are able to perform the comparisons
      with fever, and shorter, glances between the patterns. These and other findings
      suggest that skilled sight-reading is associated with an ability to rapidly
      perceive notes or groups of notes in the score, and confirm that the pattern
      matching paradigm is a useful tool in examining expertise in music reading.

PMID- 9158324
TI  - Time-till-breakdown and scalp electrical potential maps of long-range apparent
      motion.
AB  - A series of psychophysical and electrophysiological experiments is reported using
      the apparent motion (AM) breakdown effect. Breakdown describes an effect in AM in
      which, during continuous viewing, the percept of smooth of a single stimulus
      alternates with the percept of two discrete alternating stimuli. Visual evoked
      potentials (VEPs) were recorded during periods of motion or breakdown
      ("nonmotion") in horizontal and vertical displays. VEPs were compared with
      synthetic VEPs ("composite-flash") produced by adding VEPs to each element of the
      display recorded in isolation. Subtraction of VEPs was used in an attempt to
      compare the electrical responses with the processing of information relating to
      the form of the stimulus, subthreshold motion processing, and suprathreshold
      motion processing. The results, presented as scalp electrical potential
      distribution maps, were interpreted as consistent with a central adaptation
      process underlying the breakdown effect. The results also indicated that the
      hemispheric asymmetries in AM VEPs described by Manning, Finlay, and Fenelon
      (1988) were most likely due to the position of the stimuli in the visual field,
      rather than as a lateralization of motion processes per se. The results also
      provided evidence that the subthreshold and suprathreshold motion responses to
      the display were the product of different populations of motion units.

PMID- 9158325
TI  - Manipulating the disengage operation of covert visual spatial attention.
AB  - Processes of covert visual spatial attention have been closely linked to the
      programming of saccadic eye movements. In particular, it has been hypothesized
      that the reduction in saccadic latency that occurs in the gap paradigm is due to
      the prior disengagement of covert visual spatial attention. This explanation has
      received considerable criticism. No study as yet as attempted to demonstrate a
      facilitation of the disengagement of attention from a covertly attended object.
      If such facilitation were possible, it would support the hypothesis that the
      predisengagement of covert attention is necessary for the generation of express
      saccades. In two experiments using covert orienting of visual attention tasks
      (COVAT), with a high probability that targets would appear contralateral to the
      cued location, we attempted to facilitate the disengagement of covert attention
      by extinguishing peripheral cues prior to the appearance of targets. We
      hypothesized that the gap between cue offset and target onset would facilitate
      disengagement of attention from a covertly attended object. For both experiments,
      responses to targets appearing after a gap were slower than were responses in the
      no-gap condition. These results suggest that the prior offset of a covertly
      attended object does not facilitate the disengagement of attention.

PMID- 9158326
TI  - The influence of adaptation and stochastic fluctuations on spontaneous perceptual
      changes for bistable stimuli.
AB  - Spontaneous perceptual change was studied by measuring the probabilities of the
      first two spontaneous pattern switches as a function of time following the onset
      of a bistable apparent quartet for which either horizontal or vertical motion is
      perceived. Contrary to the classical satiation hypothesis (Kohler & Wallach,
      1944), differential time-dependent adaptation of the perceived compared with the
      unperceived motion directions was not necessary to account for the first
      spontaneous switch. In addition, adaptation of the perceived motion accompanied
      by recovery from adaptation of the unperceived motion was not necessary to
      account for the increased probability of the second spontaneous switch. It was
      concluded that regardless of possible adaptation effects, stochastic fluctuations
      are necessary for the actual reversal of activation levels that produces the
      spontaneous switch. When the difference in detector activation is reduced by
      differential adaptation of competing motion detectors (or by the occurrence of a
      prior spontaneous pattern change), smaller stochastic fluctuations are sufficient
      to reverse the relative activation of competing detectors. Thus, adaptation can
      increase the probability of spontaneous switches without directly causing them.

PMID- 9158327
TI  - Latency dependence of word-initial letter integration by the saccadic system.
AB  - Two experiments are reported in which saccadic eye movements were examined when
      the eyes moved to words in which the properties of the word-initial letters
      differed. It was found that the effect of saccade latency on landing position
      depended on the properties of the word-initial letters. Under short saccade
      latencies, landing positions deviated toward the word beginning in the presence
      of orthographically irregular/informative beginning (OI/IB) letters. This result
      is interpreted as an influence of the orthographic encoding process that has
      detected an unusual letter grouping. With longer saccade latencies, an increase
      of the saccade size was observed for OI/IB words, whereas orthographically
      regular/uninformative beginning words did not show the effect. It is suggested
      that this may be a consequence of the dynamics of parafoveal word information
      processing.

PMID- 9158328
TI  - Effects of amount of attention allocated to the location of visual stimulus pairs
      on perception of simultaneity.
AB  - This study was examined whether a change in the amount of attention equally
      allocated to two locations affects judgments of the simultaneity or
      successiveness of stimuli presented at those locations. Observers were cued to
      expect two brief flashes either to the left and right of fixation or above and
      below fixation. Stimulus onset asynchrony was randomly varied. On a small
      proportion of trials, the stimuli appeared at the unexpected locations. Observers
      were more likely to report the stimuli as simultaneous when they appeared in the
      unexpected locations. A model proposed to account for the data assumes that a
      brief stimulus event is represented by a probability distribution reflecting the
      uncertainty in determining the time of the event's occurrence, and two events are
      judged to be simultaneous if they are perceived to fall within some critical
      temporal interval, c, which is a function of the amount of attention allocated to
      the task.

PMID- 9158329
TI  - Visual feature integration and focused attention: response competition from
      multiple distractor features.
AB  - Predictions from Treisman's feature integration theory of attention were tested
      in a variant of the response-competition paradigm. Subjects made choice responses
      to particular color-shape conjunctions (e.g., a purple cross vs. a green circle)
      while withholding their responses to the opposite conjunctions (i.e., a purple
      circle vs. a green cross). The results showed that compatibility effects were
      based on both distractor color and shape. For unattended distractors in preknown
      irrelevant positions, compatibility effects were equivalent for conjunctive
      distractors (e.g., a purple cross and a blue triangle) and for disjunctive
      distractors (e.g., a purple triangle and a blue cross). Manipulation of attention
      to the distractors positions resulted in larger compatibility effects from
      conjoined features. These results accord with Treisman's claim that correct
      conjunction information is unavailable under conditions of inattention, and they
      provide new information on response-competition effects from multiple features.

PMID- 9158330
TI  - Time-distance relations in shifting attention between locations on one's body.
AB  - Does the time to discriminate the presence or absence of a tactile stimulus
      depend on its distance from the bodily location to which one has been attending?
      Subjects were tested by the presentation of air puffs at four of eight possible
      locations on the body. In each trial of Experiment 1, (1) subjects attended
      auditorily to an announcement of one of the eight locations; (2) 2 sec later, a
      second location was announced and, simultaneously, air puffs were presented at a
      randomly selected four of the eight locations; (3) the subjects reported as
      quickly as possible on whether or not air puffs had been presented at the second
      announced location. Overall, reaction times increased with the distance between
      the just-attended and the tested locations. Experiment 2 was undertaken to
      determine whether the operative distance was distance through the subject's body
      or directly through three-dimensional space. The subjects were tested as in
      Experiment 1, but with their arms and legs either side-by-side in front or spread
      out to each side. Reaction times then depended more on straight-line distance in
      space than on distance through the body.

PMID- 9158331
TI  - Detection of spatial discontinuities in first-order optical flow fields.
AB  - We investigated the extent to which the human visual system can detect
      discontinuities in first-order optical flow fields. We constructed two types of
      spatial discontinuities: a circular split field with a straight edge and a disk
      with annular surround. We used two different first-order optical flow components:
      an expansion and a rotation. We found an intriguing difference in the detection
      thresholds for straight and circular discontinuities. Whereas straight
      discontinuities yielded thresholds of 10%-50% difference in expansion or
      rotation, circular discontinuities could, at first, only be detected at extreme
      differences (>> 100%). After a learning period, thresholds for such stimuli
      decreased, but they remained significantly higher than thresholds for the
      straight edge. Thresholds rose for stimuli that formed a gradual transition
      between a circular and a straight edge, and they decreased with increasing
      eccentricity of the circular discontinuity. Results suggest that symmetry in this
      stimulus, defined by the coincidence of the center of expansion or rotation and
      the center of the circular discontinuity, was responsible for the difference in
      thresholds for circular and straight discontinuities.

PMID- 9158332
TI  - Limited visual control of the intelligibility of speech in face-to-face dialogue.
AB  - Speakers are thought to articulate individual words in running speech less
      carefully whenever additional nonacoustic information can help listeners
      recognize what is said (Fowler & Housum, 1987; Lieberman, 1963). Comparing single
      words excerpted from spontaneous dialogues and control tokens of the same words
      read by the same speakers in lists, Experiment 1 yielded a significant but
      general effect of visual context: Tokens introducing 71 new entities in dialogues
      in which participants could see one another's faces were more degraded (less
      intelligible to 54 naive listeners) than were tokens of the same words from
      dialogues with sight lines blocked. Loss of clarity was not keyed to moment-to
      moment visual behavior. Subjects with clear sight lines looked at each other too
      rarely to account for the observed effect. Experiment 2 revealed that tokens of
      60 words uttered while subjects were looking at each other were significantly
      less degraded (in length and in intelligibility to 72 subjects) vis-a-vis
      controls than were spontaneous tokens of the same words produced when subjects
      were looking elsewhere. Intelligibility loss was mitigated only when listeners
      looked at speakers. Two separate visual effects are discussed, one of the global
      availability and the other of the local use of the interlocutor's face.

PMID- 9158333
TI  - Effects of similarity, difficulty, and nontarget presentation on the time course
      of visual attention.
AB  - Long-lasting interference from an initial visual target on a subsequent one has
      been measured in two paradigms: rapid serial presentation of targets and
      nontargets at a single location, and simple presentation of two spatially
      separated targets. We note that comparisons between these paradigms might be
      invalid, since interference in each paradigm can be attributed to a different
      source: demands on selective attention, or demands to switch locations. We use a
      novel target presentation that both minimizes selection demands and eliminates
      location switching, yet we still find long-lasting interference. We suggest that
      all three paradigms discussed tap a common attentional limit. We also examine
      effects of similarity between targets, and effects of discrimination difficulty
      on the initial target. We find that similarity effects are more pronounced when
      nontargets are present, and we find no effect of discrimination difficulty on
      subsequent interference.

PMID- 9158334
TI  - Visually perceived location is an invariant in the control of action.
AB  - We provide experimental evidence that perceived location is an invariant in the
      control of action, by showing that different actions are directed toward a single
      visually specified location in space (corresponding to the putative perceived
      location) and that this single location, although specified by a fixed physical
      target, varies with the availability of information about the distance of that
      target. Observers in two conditions varying in the availability of egocentric
      distance cues viewed targets at 1.5, 3.1, or 6.0 m and then attempted to walk to
      the target with eyes closed using one of three paths; the path was not specified
      until after vision was occluded. The observers stopped at about the same location
      regardless of the path taken, providing evidence that action was being controlled
      by some invariant, ostensibly visually perceived location. That it was indeed
      perceived location was indicated by the manipulation of information about target
      distance--the trajectories in the full-cues condition converged near the physical
      target locations, whereas those in the reduced-cues condition converged at
      locations consistent with the usual perceptual errors found when distance cues
      are impoverished.

PMID- 9158335
TI  - Contours of equal perceived amplitude and equal perceived frequency for
      electrocutaneous stimuli.
AB  - Previous measurements of equal-sensation contours for electrocutaneous stimuli
      consisting of repeated bursts of biphasic pulses have shown that stimulus
      frequency has little effect on perceived amplitude, and that stimulus amplitude
      has no effect on perceived frequency. These earlier contours, however, were
      measured over a very restricted range of amplitude and frequency or for a single
      perceived amplitude or perceived frequency. Contours of equal perceived amplitude
      and equal perceived frequency were measured in the present study for stimuli
      covering most of the useable range of amplitudes and frequencies: 3-12 dB SL and
      4-64 Hz. Eight naive subjects generated contours of equal perceived amplitude at
      four reference amplitudes via Bekesy tracking, and 8 additional subjects
      generated contours of equal perceived frequency at three reference frequencies.
      The contours of equal perceived amplitude declined slightly but significantly
      with increases in stimulus frequency, consistent with previous results. The shape
      of the contours was also slightly dependent on the amplitude of the reference
      stimulus. Contours of equal perceived frequency were unaffected by stimulus
      amplitude on the average, but the contour shape did vary modestly, though
      erratically, with reference frequency.

PMID- 9158336
TI  - Visual detection and perceptual independence: assessing color and form.
AB  - Visual stimuli are multidimensional. One important perceptual problem is to
      determine how the dimensions are combined. One important aspect of dimensional
      combination is whether the dimensions are perceptually independent or
      perceptually correlated. A new task is presented--the visual detection task--that
      directly assesses the degree of perceptual correlation between any two
      dimensions. Two experiments were conducted that assess the degree of perceptual
      correlation between form and color during the early stages of perceptual
      analysis. The results show that form and color are not perceptually independent.
      In addition, the pattern of perceptual correlation found indicates that form and
      color are not processed independently. The pattern of results constrains all
      models of early vision. A model of early vision based on active signal modulation
      is proposed.

PMID- 9158337
TI  - Technology transfer: trends in the federalization of biomedical research.
AB  - Federal involvement in biomedical research has increased significantly in the
      postwar era, particularly throughout the 1980s and early 1990s. New federal laws
      and regulations now offer unprecedented opportunities to commercialize federally
      funded and conducted research, essentially creating a new field of "technology
      transfer" law. As a result, the biomedical research sector of the health care
      industry must master a number of relatively new and still developing federal
      laws, regulations, policies, and concerns that will probably continue to
      significantly affect its operations. To assist academic medical centers and
      others in understanding the federal presence in biomedical research, the authors
      give a short history of technology transfer laws and issues and summarize some of
      the current main areas of federal interest, including federal oversight of
      federally funded research, sponsored research agreements, conflict of interest,
      scientific misconduct, and the prospect of government price control over some
      biomedical inventions. The authors caution academic medical centers to realize
      that recent trends favoring deregulation and budget cutting could diminish
      federal involvement in the future. Thus, research institutions should keep
      abreast not only of existing rules and policies but of ongoing legislative and
      regulatory activities that portend possible changes.

PMID- 9158338
TI  - Advice to individuals involved in misconduct accusations.
AB  - The author offers advice to faculty, students, and staff who become involved in
      issues of research misconduct, whether as the accuser or as the accused. After
      reviewing the different definitions of research misconduct used by various
      authorities and discussing other kinds and degrees of misconduct, he provides
      information to those who suspect research misconduct, to help them identify their
      responsibilities and the risks involved: he makes it clear that an accusation of
      research fraud or other misconduct has serious consequences for all parties. The
      author then discusses how to pursue concerns about improper research practices,
      emphasizing a nonconfrontational approach and the use of proper channels for
      reporting. He explains the process of a formal review, including characteristic
      institutional responses; the role of the Office of Research Integrity; and when
      to seek the advice of an attorney. He argues that education is clearly preferable
      to denunciation as a way to improve scientists' ethics and practices. The author
      then gives similarly detailed advice to the accused, including a caution not to
      take criticism of methods or results as an accusation of fraud. He discusses the
      significances of the two stages of review of an allegation of misconduct, with
      practical advice for cooperative participation in any review; use of legal
      counsel; the importance of avoiding retaliation; information about due process
      and material evidence; the impact of a formal investigation; peer standards for
      evaluating misconduct; and the unavoidable discomfort that the accused will
      experience during the lengthy process. He advises that practicing good science is
      the first step in avoiding this unpleasant experience.

PMID- 9158339
TI  - "Without handicap": issues of medical schools and physically disabled students.
AB  - The Americans with Disabilities Act of 1990 requires that access to education not
      be denied simply on the basis of disability. The law requires definition of
      "basic qualifications" required of all applicants, "essential elements" of the
      curriculum, and whether accommodation would alter the "fundamental nature" of the
      learning experience or impose "undue burden." Medical schools have a very low
      proportion of physically disabled students, which the author argues is largely a
      result of schools' conception of the "undifferentiated graduate" as being capable
      of performing the history, physical examination, and any medical procedure
      without an intermediary. But the author maintains that medical students need not
      be unblemished physically; medical educators' obligation is to educate those
      students who are qualified to become physicians by virtue of intelligence,
      professional attitude, and ability to effectively interact and communicate. With
      respect to clinical training, it is important to consider whether personal, hands
      on experience is required for adequate learning to occur. Because most physicians
      limit the scopes of their practices and do not perform all procedures, because
      those physicians who develop physical disabilities are not precluded from
      continuing in some forms of medical practice, and because technologic advances
      allow for the substitution of imaging and diagnostic testing for the more
      conventional approach to the physical examination, the requirement for hands-on
      capability becomes less compelling. Yet not every physically disabled applicant
      should be admitted to medical school, and those admitted require coaching,
      guidance, and career advice in order to succeed with their physical limitations.
      The author suggests that one of the seminal concepts of medical education,
      "without handicap," should be seen not as referring to the pre-existing physical
      status of students but instead as the obligation of educators to provide all
      their students with the broadest possible learning experiences so that they will
      be without the handicap of inadequate education when they proceed to their chosen
      fields.

PMID- 9158340
TI  - Taking suffering seriously: a new role for the medical case history.
AB  - The relief of suffering is commonly cited as a principal goal of clinical
      medicine. Yet suffering receives little attention in medical case histories,
      except for symptoms of pain or dysfunction that are useful diagnostically or in
      following the course of known disease and evaluating the effects of treatment.
      Contemporary attempts to deal more formally with suffering--the patient's
      personal experience of sickness or disability--by recording that information in
      case histories and medical records began with the problem-oriented medical record
      and continue with various proposals to include the "patient's perspective" or the
      "patient's review" in case presentations or records of medical care. Medicine's
      commitment to the relief of suffering is a compelling warrant to make the
      identification of the patient's perspective a major goal of historical inquiry
      and representation, beginning with a "history of present illness" that describes
      the patient's sickness or disability from two perspectives: that of the disease
      (a biomedically oriented account of the patient's sickness) and that of the
      illness (a description of the patient's personal situation, sufferings,
      perplexities, hopes, and fears). Experience with an earlier version of this
      reform suggests that optimal understanding and implementation of such a dual
      perspective history by students and their instructors requires concomitant study
      of such matters as the goals of clinical medicine and the nature of suffering.

PMID- 9158341
TI  - Excellence in clinical teaching: the core of the mission.
AB  - The core of clinical education is the dialogue between physician teachers and
      their students and residents. Several years ago the authors began to examine the
      nature of the "talk" in one-on-one ambulatory clinical teaching encounters.
      Discourse analysis, a qualitative method for examining communication, can
      identify patterns of interaction and can highlight the factors that impede useful
      teaching conversation and learning in the contexts of clinical education.
      Further, it can identify the microskills that physician-teachers need to teach
      effectively and humanistically. Having faculty members coach each other is an
      effective institutional approach to teaching these microskills, and it is
      especially valuable to have teachers examine the language they use in clinical
      teaching, so that they can understand the different impacts that different kinds
      of language can have on learners. Physicians are responsible for cultivating
      humanistic attitudes in their students. When a physician is humanistic in helping
      a student learn, the student can, in turn, use the same attributes with the
      patient. The humanistic behaviors that are valuable parts of the physician
      patient relationship are the same ones that must also characterize the
      relationship between physicians and their students. Excellent one-on-one teaching
      in clinical settings requires two major things: first, medical educators must
      understand the special communication skills that create effective and humanistic
      teaching; and second, administrators must re-recognize that teaching is the true
      heart of our medical schools and teaching hospitals, and therefore support the
      faculty professional development needed to foster excellent teaching.

PMID- 9158342
TI  - Fifteen years of a videotape review program for internal medicine and medicine
      pediatrics residents.
AB  - The medical interview remains the most valuable component in patient evaluation.
      In addition to its diagnostic usefulness, it is the foundation upon which the
      doctor-patient relationship is built. It is essential, therefore, that health
      care providers be well trained in interviewing. Evidence suggests that having
      residents conduct videotaped interviews with patients and review the videotapes
      with faculty is an excellent way to teach interviewing skills. Videotape review
      has been part of the residency programs in primary care internal medicine and
      medicine-pediatrics at Wayne State University School of Medicine for 15 years.
      Throughout the history of the videotape program, the authors have endeavored to
      make the review process less stressful for residents by ensuring that the reviews
      are nonthreatening, nonjudgmental, and learner-centered. In this paper, the
      authors discuss (1) the structure and process of the videotape review program;
      (2) recurrent themes of the review sessions; (3) residents' perspectives on the
      process; and (4) potential barriers to a successful videotape review program and
      suggestions for how to avoid or overcome them.

PMID- 9158343
TI  - The commerce of ideas: Internets and Intranets.
AB  - Academic physicians pride themselves on their intelligent use of medical
      technology, their innovativeness, and their ability to market their excellence to
      the public. Although this pride is extraordinarily justified in the areas of
      clinical medicine, biomedical research, and health sciences education, academic
      physicians have less reason to be proud of their accomplishments in the area of
      information management. In years past, a lack of attention to coherent
      information management had few consequences so long as there were foci of
      excellence in clinical disciplines, libraries, core research laboratories, and
      selected training programs. But the widespread adoption of network-based
      communications has changed both the priorities of faculty and the information
      infrastructure necessary to maintain a competitive advantage. In the arena of
      health care information technology, many medical centers have chosen
      indiscriminate consumption over focused leadership. This essay speculates on how
      technologies based on the World Wide Web (WWW) may affect academic medicine
      through both the greater penetration of the Internet and a wider use of internal
      "intranets." The Internet is transforming the landscape of biomedical publishing,
      biomedical education, and the hospital library. The intranet is becoming a vital
      means of providing documents to support the administration of academic medicine
      and, in many circumstances, the delivery of patient-specific information.
      Although there is great potential for transformation, many academic medical
      centers have not yet fully demonstrated either the wisdom to advance a great
      information-technology vision or the will necessary to turn a vision into a
      coherent plan of action.

PMID- 9158344
TI  - Restructuring VA ambulatory care and medical education: the PACE model of primary
      care.
AB  - The Veterans Health Administration (VHA) Western Region and associated medical
      schools formulated a set of recommendations for an improved ambulatory health
      care delivery system during a 1988 strategic planning conference. As a result,
      the Department of Veterans Affairs (VA) Medical Center in Sepulveda, California,
      initiated the Pilot (now Primary) Ambulatory Care and Education (PACE) program in
      1990 to implement and evaluate a model program. The PACE program represents a
      significant departure from traditional VA and non-VA academic medical center
      care, shifting the focus of care from the inpatient to the outpatient setting.
      From its inception, the PACE program has used an interdisciplinary team approach
      with three independent global care firms. Each firm is interdisciplinary in
      composition, with a matrix management structure that expands role function and
      empowers team members. Emphasis is on managed primary care, stressing a
      biopsychosocial approach and cost-effective comprehensive care emphasizing
      prevention and health maintenance. Information management is provided through a
      network of personal computers that serve as a front end to the VHA Decentralized
      Hospital Computer Program (DHCP) mainframe. In addition to providing
      comprehensive and cost-effective care, the PACE program educates trainees in all
      health care disciplines, conducts research, and disseminates information about
      important procedures and outcomes. Undergraduate and graduate trainees from 11
      health care disciplines rotate through the PACE program to learn an integrated
      approach to managed ambulatory care delivery. All trainees are involved in a
      problem-based approach to learning that emphasizes shared training experiences
      among health care disciplines. This paper describes the transitional phases of
      the PACE program (strategic planning, reorganization, and quality improvement)
      that are relevant for other institutions that are shifting to training programs
      emphasizing primary and ambulatory care.

PMID- 9158345
TI  - Evaluation of the VA's Pilot Program in Institutional Reorganization toward
      Primary and Ambulatory Care: Part I, Changes in process and outcomes of care.
AB  - PURPOSE: To evaluate the impact of the reorganization of an academic Veterans
      Affairs medical center toward primary and ambulatory care--including the
      implementation of a medical-center-wide interdisciplinary firm system and
      ambulatory care training program--on the quality of primary ambulatory care.
      METHOD: Randomly selected male veterans visiting the Veterans Affairs Medical
      Center in Sepulveda, California, were surveyed in 1992, early in the
      implementation of the program, and in 1993, after the program had been fully
      implemented. Two surveys were used: one before the veterans saw their primary
      care providers (practice-based survey) and the other immediately after patient
      visits (visit-based survey). Survey-participant data were then linked to
      computerized utilization and mortality data. Survey topics were mapped to the
      medical center's strategic plan and goals for ambulatory care, and focused on
      patients' reports about the care they had received in terms of continuity,
      access, preventive care, and other aspects of the biopsychosocial model of care.
      Administrative computer data were then used to evaluate effects on medical center
      workload. Statistical analyses included analysis of variance, analysis of
      covariance, chi-square, and logistic regression. RESULTS: For practice-based
      comparisons, complete data were available for 1,262 veterans in 1992 and 1,373 in
      1993. For visit-based comparisons, complete data were available for 1,407
      veterans in 1992 and 643 in 1993. Results included statistically significant
      improvements in continuity of care and detection of depression as well as
      increased rates of preventive care counseling (smoking and exercise). The
      proportion of veterans reporting being seen by physicians increased, as did the
      proportion of patients seen for check-ups rather than for acute problems. Fewer
      patients were seen in subspecialty clinics than in general medicine clinics.
      Patient satisfaction increased, hospitalizations decreased, and death rates
      decreased. Alcohol counseling and access to care for acute symptoms declined.
      Workload shifted from subspecialists to generalists and from inpatient care to
      outpatient care. CONCLUSION: The institutional reorganization toward primary and
      ambulatory care succeeded in substantially improving the quality of ambulatory
      care, reflecting improvements in the system of care and of health care provider
      training in ambulatory care.

PMID- 9158346
TI  - Evaluation of the VA's Pilot Program in Institutional Reorganization Toward
      Primary and Ambulatory Care: Part II, A study of organizational stresses and
      dynamics.
AB  - BACKGROUND: Many academically affiliated hospitals are moving from an inpatient,
      subspecialty orientation in their patient care and educational programs toward a
      greater emphasis on ambulatory and primary care. Few studies have focused on the
      organizational, staffing, and management issues involved in implementing these
      changes. METHOD: The authors carried out a qualitative evaluation of the process
      of change in an academic Department of Veterans Affairs hospital during
      implementation of a major ambulatory primary care program. They interviewed four
      top managers individually and 59 top and middle managers, house officers, and
      patients in focus groups in the spring of 1992, nine months after implementation
      of the key components of the program. Four raters independently evaluated written
      transcripts of focus-group sessions and identified themes. RESULTS: The main
      problems identified were difficulty with administrative integration between
      inpatient and outpatient services; need for training, retraining, and
      orientation; tensions due to changes in roles and organizational culture; and
      inefficiency due to the need for frequent negotiations in daily work life. These
      four problems reflected tensions associated with new demands imposed by matrix
      management, changing job descriptions, policies and procedures, and changing
      patterns of communication and record keeping. CONCLUSION: During the process of
      implementation of a primary care focus throughout a medical center, extra demands
      upon staff are inevitable and should be anticipated and planned for. Twelve key
      factors for successful organizational change are discussed.

PMID- 9158347
TI  - Necessity for an animal model of postoperative pain.

PMID- 9158348
TI  - Economics of anesthesia care. A call to arms!

PMID- 9158349
TI  - Why must the practice of anesthesiology change? It's economics, doctor!

PMID- 9158350
TI  - Sodium channel in human malignant hyperthermia.
AB  - BACKGROUND: The abundance of a specific sodium channel subunit (SkM2) appeared to
      be altered in vitro in cell cultures from persons susceptible to malignant
      hyperthermia. This study sought to determine whether these findings are artifacts
      of cell culture or whether they may be relevant to malignant hyperthermia.
      METHODS: Regulation of transcript levels of SkM2, a specific sodium channel alpha
      subunit, was determined by mRNA analysis. Functional SkM2 protein was estimated
      in biopsy sections of vastus lateralis muscle by inhibiting the directly elicited
      muscle twitch by tetrodotoxin, which can differentiate at least three sodium
      currents in skeletal muscle. RESULTS: The transcript levels of SkM2 were
      depressed by 115-fold in six of seven persons susceptible to malignant
      hyperthermia; and the functional expression of the SkM2 protein, based on the
      tetrodotoxin sensitivity of the directly elicited twitch, was decreased by at
      least fourfold in muscle from persons susceptible to malignant hyperthermia
      compared with persons who were not susceptible. CONCLUSIONS: As in previous
      studies in cell culture, altered mRNA and/or the functional expression of a
      specific subunit of the sodium channel (SkM2) was found in biopsy sections of
      muscle from all 12 persons examined who were susceptible to malignant
      hyperthermia but in none of the 16 nonsusceptible participants. Human malignant
      hyperthermia is a heterogeneous disorder, and the down-regulation of SkM2 may be
      involved in the final common pathway through which mutations in any one of
      several proteins, including the ryanodine receptor, could render a person
      susceptible.

PMID- 9158351
TI  - Continuous epidural blockade arrests the postoperative decrease in muscle protein
      fractional synthetic rate in surgical patients.
AB  - BACKGROUND: Epidural anesthesia with local anesthetics is associated with
      postoperative attenuation of nitrogen loss. The protein-sparing effect could be
      the result of either a decreased protein breakdown or increased protein
      synthesis. Although the role of epidural local anesthetics in effectively
      limiting the increase in postoperative protein breakdown is established at the
      whole-body level, it is necessary to determine whether the muscle protein
      fractional synthetic rate is directly modulated when nociceptive stimuli are
      blocked. METHODS: Twelve otherwise healthy patients scheduled for elective
      colorectal surgery, who were receiving a constant intake of nitrogen (0.1 kg
      1.day-1) and calories (20 kcal.kg-1.day-1) before and after surgery, were
      randomly assigned to receive either general anesthesia (with thiopentone,
      vecuronium, fentanyl, or enflurane; control group, n = 6) or epidural anesthesia
      (T3-S5 sensory block with 0.75% bupivacaine) and general anesthesia (epidural
      group, n = 6). In the control group, postoperative analgesia was achieved with
      papaveretum given subcutaneously, whereas a continuous epidural bupivacaine
      infusion (T8-L5 sensory block) was maintained for 48 h in the epidural group. The
      postabsorptive muscle protein fractional synthetic rate was determined using a 6
      h continuous infusion of 13C-labeled leucine (1 mg.kg-1.h-1), and the 13C
      enrichment in muscle biopsy specimens before surgery and 48 h after surgery was
      measured. RESULTS: Plateau 13C enrichment of plasma alpha-ketoisocaproate (taken
      to represent the intracellular leucine precursor pool enrichment for protein
      synthesis) was achieved during the 6-h infusion (mean coefficient of variation
      was 2.8%). Muscle protein synthesis at 48 h after operation compared with
      preoperative levels decreased significantly in the control group (P = 0.03). In
      contrast, it increased by 25% in the epidural group. Although this was not
      significantly (P = 0.15) different from preoperative levels, it was significantly
      greater than in the control patients. CONCLUSIONS: Epidural infusion of local
      anesthetics begun before surgery and continued during the first 48 h after
      operation significantly attenuates the decrease in the postabsorptive muscle
      protein synthesis rate associated with surgical injury. Effective block of
      nociceptive stimuli thus preserves tissue protein synthesis.

PMID- 9158352
TI  - Bronchoscopy via a redesigned Combitube in the esophageal position. A clinical
      evaluation.
AB  - BACKGROUND: The esophageal-tracheal Combitube (Kendall-Sheridan Catheter Corp.,
      Argyle, NY) is an effective device for providing adequate gas exchange. However,
      tracheal suctioning is impossible with the Combitube placed in the esophageal
      position. To eliminate this disadvantage, the Combitube was redesigned by
      creating an enlarged hole in the pharyngeal lumen that allows fiberoptic access,
      tracheal suctioning, and tube exchange over a guide wire. METHODS: The two
      anterior, proximal perforations of regular Combitubes were replaced by a larger,
      ellipsoid-shaped hole. After the study was approved by the institutional review
      board, 20 patients with normal airways (Mallampati I or II) were studied. During
      general anesthesia, patients were esophageally intubated with the Combitube. A
      flexible bronchoscope was inserted and guided via the modified hole and glottic
      opening down the trachea. For the replacement procedure, a J tip guide wire was
      introduced through the bronchoscope. The bronchoscope and the Combitube were
      removed and a standard endotracheal tube was advanced over a guide catheter.
      RESULTS: Bronchoscopic evaluation of the trachea and guided replacement of the
      Combitube by an endotracheal tube was successful in all 20 study patients. The
      average time needed to perform airway exchange was 90 +/- 20 s (mean +/- SD).
      Arterial oxygen saturation and end-tidal carbon dioxide levels remained normal in
      all patients. No case of laryngeal trauma was observed during intubation or the
      airway exchange procedure. CONCLUSIONS: The redesigned Combitube enables
      fiberoptic bronchoscopy, fine-tuning of its position in the esophagus, and guided
      airway exchange in patients with normal airways. Further studies are warranted to
      demonstrate its value in patients with abnormal airways.

PMID- 9158353
TI  - Meperidine decreases the shivering threshold twice as much as the
      vasoconstriction threshold.
AB  - BACKGROUND: Meperidine administration is a more effective treatment for shivering
      than equianalgesic doses of other opioids. However, it remains unknown whether
      meperidine also profoundly impairs other thermoregulatory responses, such as
      sweating or vasoconstriction. Proportional inhibition of vasoconstriction and
      shivering suggests that the drug acts much like alfentanil and anesthetics but
      possesses greater thermoregulatory than analgesic potency. In contrast,
      disproportionate inhibition would imply a special antishivering mechanism.
      Accordingly, the authors tested the hypothesis that meperidine administration
      produces a far greater concentration-dependent reduction in the shivering than
      vasoconstriction threshold. METHODS: Nine volunteers were each studied on three
      days: 1) control (no opioid); 2) a target total plasma meperidine concentration
      of 0.6 microgram/ml (40 mg/h); and 3) a target concentration of 1.8 micrograms/ml
      (120 mg/h). Each day, skin and core temperatures were increased to provoke
      sweating and then subsequently reduced to elicit vasoconstriction and shivering.
      Core-temperature thresholds (at a designated skin temperature of 34 degrees C)
      were computed using established linear cutaneous contributions to control
      sweating (10%) and vasoconstriction and shivering (20%). The dose-dependent
      effects of unbound meperidine on thermoregulatory response thresholds was then
      determined using linear regression. Results are presented as means +/- SDs.
      RESULTS: The unbound meperidine fraction was approximately 35%. Meperidine
      administration slightly increased the sweating threshold (0.5 +/- 0.8 degree
      C.microgram-1.ml; r2 = 0.51 +/- 0.37) and markedly decreased the vasoconstriction
      threshold (-3.3 +/- 1.5 degrees C.microgram-1.ml; r2 = 0.92 +/- 0.08). However,
      meperidine reduced the shivering threshold nearly twice as much as the
      vasoconstriction threshold (-6.1 +/- 3.0 degrees C.microgram-1.ml; r2 = 0.97 +/-
      0.05; P = 0.001). CONCLUSIONS: The special antishivering efficacy of meperidine
      results at least in part from an uncharacteristically large reduction in the
      shivering threshold rather than from exaggerated generalized thermoregulatory
      inhibition. This pattern of thermoregulatory impairment differs from that
      produced by alfentanil, clonidine, propofol, and the volatile anesthetics, all
      which reduce the vasoconstriction and shivering thresholds comparably.

PMID- 9158354
TI  - Reduction of the minimum alveolar concentration of isoflurane by dexmedetomidine.
AB  - BACKGROUND: alpha 2-Adrenergic agonists have been shown to reduce anesthetic
      requirements of other anesthetics, and they may even act as complete anesthetics
      by themselves at high doses in animal models. The present study was designed to
      define the interaction of intravenous infusion of dexmedetomidine, an alpha 2
      adrenergic agonist, and isoflurane in patients having surgery by using the
      minimum alveolar concentration (MAC) of isoflurane as the measure of anesthetic
      potency. METHODS: Forty-nine women scheduled for abdominal hysterectomy were
      randomly allocated to receive either a placebo infusion (n = 16) or a two-stage
      infusion of dexmedetomidine with target plasma concentration of 0.3 ng/ml (n =
      17) or 0.6 ng/ml (n = 16). The study drug infusion was commenced 15 min before
      induction of anesthesia with thiopental and alfentanil and was continued until
      skin incision. The end-tidal concentration of isoflurane for each patient was
      predetermined according to the "up-down" method of Dixon, and it was maintained
      for at least 15 min before the patient's response to skin incision was assessed.
      RESULTS: The MAC of isoflurane was 0.85% end-tidal in the control group, 0.55%
      end-tidal with the low dose of dexmedetomidine, and 0.45% end-tidal with the high
      dose of dexmedetomidine. CONCLUSIONS: The MAC of isoflurane in the control group
      was lower than that reported previously in similar patients having surgery,
      probably due to anesthesia induction with thiopental and alfentanil.
      Nevertheless, with the high dose of dexmedetomidine, the MAC of isoflurane was
      still 47% less than that without dexmedetomidine.

PMID- 9158355
TI  - Rehydration of desiccated Baralyme prevents carbon monoxide formation from
      desflurane in an anesthesia machine.
AB  - BACKGROUND: Desiccated carbon dioxide absorbents degrade desflurane, enflurane,
      and isoflurane to carbon monoxide (CO) in vitro and in anesthesia machines, which
      can result in significant clinical CO exposure. Carbon monoxide formation is
      highest from desflurane, and greater with Baralyme than with soda lime.
      Degradation is inversely related to absorbent water content, and thus the
      greatest CO concentrations occur with desflurane and fully desiccated Baralyme.
      This investigation tested the hypothesis that rehydrating desiccated absorbent
      can diminish CO formation. METHODS: Baralyme was dried to constant weight. Carbon
      monoxide formation from desflurane and desiccated Baralyme was determined in
      sealed 20.7-ml vials without adding water, after adding 10% of the normal water
      content (1.3% water), and after adding 100% of the normal water content (13%
      water) to the dry absorbent. Similar measurements were made using an anesthesia
      machine and circle system. Carbon monoxide was measured by gas chromatography
      mass spectrometry. RESULTS: Carbon monoxide formation from desflurane in vitro
      was decreased from 10,700 ppm with desiccated Baralyme to 715 ppm and less than
      100 ppm, respectively, when 1.3% and 13% water were added. Complete rehydration
      also decreased CO formation from enflurane and isoflurane to undetectable
      concentrations. Desflurane degradation in an anesthesia machine produced 2,500
      ppm CO in the circuit, which was reduced to less than 180 ppm when the full
      complement of water (13%) was added to the dried absorbent. CONCLUSIONS:
      Desflurane is degraded by desiccated Baralyme in an anesthesia machine, resulting
      in CO formation. Adding water to dried Baralyme is an effective means of reducing
      CO formation and the risk of intraoperative CO poisoning. Although demonstrated
      specifically for desflurane and Baralyme, rehydration is also applicable to
      enflurane and isoflurane, and to soda lime.

PMID- 9158356
TI  - Effect of systemic and intrathecal morphine in a rat model of postoperative pain.
AB  - BACKGROUND: To learn more about persistent pain after an incision, a rat model
      for postoperative pain has been developed. To further evaluate this model, the
      authors examined the effect of intrathecal (IT) and subcutaneous (SC) morphine,
      effective for postoperative pain relief in patients, on pain behaviors
      immediately after surgery and 1 day after surgery. METHODS: Rats were
      anesthetized with halothane, and a 1-cm incision was made in the plantar aspect
      of the foot and closed. After recovery, the rats were placed on an elevated
      plastic mesh floor, and withdrawal threshold was determined using calibrated von
      Frey filaments (15-522 mN) applied from beneath the test cage to an area adjacent
      to the wound at the heel. Pain behaviors also were assessed using the response
      frequency to a nonpunctate mechanical stimulus and a cumulative pain score.
      RESULTS: Mechanical hyperalgesia and nonevoked pain behaviors were present on the
      day of surgery and 1 day after surgery. Administration of either SC (0.3-3.0
      mg/kg) or IT (0.16-5.0 micrograms) morphine reversibly increased the withdrawal
      threshold. The response frequency to the nonpunctate stimulus and the nonevoked
      pain scores also were decreased by 3 mg/kg of SC or 5 micrograms of IT morphine.
      Naloxone (1 mg/kg) reversed morphine-produced hypoalgesia. CONCLUSION: This is
      the first study to demonstrate that mechanical hyperalgesia to a nonpunctate
      stimulus occurs after a surgical incision in the rat. This rat model of
      postoperative has several similarities to postoperative patients: mechanical
      hyperalgesia to punctate and nonpunctate stimuli, nonevoked pain, and pain
      behaviors inhibited by SC and IT morphine. This model also may be useful for
      predicting analgesia by investigational agents for postoperative pain.

PMID- 9158357
TI  - Isoflurane- and halothane-mediated dilation of distal bronchi in the rat depends
      on the epithelium.
AB  - BACKGROUND: Respiratory epithelium releases substance(s) that can modulate
      bronchoconstriction in response to constrictive agonists and enhance
      bronchodilation in response to certain bronchodilators. The hypothesis that the
      bronchodilatory effect of isoflurane and halothane depends on the epithelium was
      tested in rat distal bronchial segments. METHODS: Wistar rat bronchial segments
      of the fourth order (diameter approximately 100 microns) were dissected. After
      preconstriction with 5-hydroxytryptamine, each bronchial segment was exposed to
      increasing concentrations of 0% to 3% isoflurane or 0% to 3% halothane under four
      conditions: after epithelial rubbing, after pretreatment with the nitric oxide
      synthase inhibitor NG-nitro-L-arginine, after pretreatment with the
      cyclooxygenase inhibitor indomethacin, or with no preintervention (control).
      Changes in bronchial diameter were monitored using an in vitro video detection
      system. RESULTS: Both isoflurane and halothane produced concentration-dependent
      bronchodilation (P < 0.001 for either anesthetic; 40% +/- 11% [mean +/- SD]
      dilation for 3% isoflurane and 57% +/- 10% dilation for 3% halothane). For both
      anesthetics, bronchodilation was significantly but incompletely attenuated by
      epithelial rubbing (12% +/- 7% dilation for 3% isoflurane [P < 0.01] and 31% +/-
      10% dilation for 3% halothane [P < 0.01]), by pretreatment with indomethacin (20%
      +/- 8% dilation for 3% isoflurane [P < 0.02] and 21% +/- 9% dilation for 3%
      halothane [P < 0.001]), or by L-NNA (9% +/- 7% dilation for 3% isoflurane [P <
      0.005] and 39% +/- 12% dilation for 3% halothane [P < 0.05]). Epithelial rubbing
      did not impair nitroprusside-associated bronchodilation. CONCLUSIONS: Isoflurane-
      and halothane-mediated bronchodilation depends at least partially on the
      epithelium and may involve both a prostanoid and nitric oxide in distal rat
      bronchi.

PMID- 9158358
TI  - Alterations in canine left ventricular-arterial coupling and mechanical
      efficiency produced by propofol.
AB  - BACKGROUND: Propofol reduces blood pressure by decreasing left ventricular (LV)
      afterload and myocardial contractility. This investigation tested the hypothesis
      that propofol preserves LV-arterial coupling and mechanical efficiency because of
      these simultaneous hemodynamic actions. METHODS: Experiments were conducted in
      open-chest dogs (n = 8) instrumented for measurement of aortic and LV pressure,
      dP/dtmax, and LV volume. Myocardial contractility was assessed with the slope
      (Ees) of the LV end systolic pressure-volume relationship. Effective arterial
      elastance (En; the ratio of end systolic arterial pressure to stroke volume),
      stroke work (SW), and pressure-volume area (PVA) were determined from the LV
      pressure-volume relationships. Dogs were studied 30 min after instrumentation and
      after 15-min intravenous infusions of propofol at 5, 10, 20, and 40 mg.kg-1.h-1.
      RESULTS: Propofol caused dose-dependent decreases in Ees (4.7 +/- 0.9 during
      control to 2.7 +/- 0.5 mmHg/ml during the high dosage) and dP/dtmax, indicating a
      direct negative inotropic effect. Ea increased at the 10 mg.kg-1.h-1 dose of
      propofol but decreased at higher dosages. Propofol decreased the ratio of Ees to
      Ea (0.88 +/- 0.13 during control to 0.56 +/- 0.10 during the high dosage),
      consistent with impairment of LV-arterial coupling. Propofol also reduced the
      ratio SW to PVA (0.54 +/- 0.03 during control to 0.45 +/- 0.03 during the 20
      mg.kg-1.h-1), suggesting a decline in LV mechanical efficiency. SW and PVA
      recovered toward baseline values at the 40 mg.kg-1.h-1 dose. CONCLUSIONS:
      Although propofol depresses mechanical matching of the LV to the arterial system
      and reduces LV efficiency, these alterations plateau at higher dosages of
      propofol because reductions in afterload begin to offset further declines in
      myocardial contractile function.

PMID- 9158359
TI  - A physiologic assessment of intrathecal amitriptyline in sheep.
AB  - BACKGROUND: Intrathecal injection of amitriptyline enhances antinociception from
      intravenous morphine and reduces neuropathic pain behavior in animals. This study
      represents part of a preclinical assessment of intrathecal amitriptyline to
      determine its safety for use in humans. METHODS: Low thoracic intrathecal,
      femoral, and pulmonary arterial catheters were inserted in 18 adult ewes,
      followed 96 h later by intrathecal injection of saline or 5 mg amitriptyline and
      by determination of spinal cord blood flow, hemodynamic variables, behavioral
      changes, cerebrospinal fluid concentrations of catecholamines and amitriptyline,
      and spinal tissue concentrations of amitriptyline. In six other ewes, low
      thoracic intrathecal and femoral arterial catheters were inserted and blood
      pressure and heart rate were measured after intrathecal injection of saline or
      0.25, 1, or 5 mg amitriptyline. Four other ewes received cervical intrathecal
      injection of 5 and 10 mg amitriptyline, and antinociception was determined.
      RESULTS: Thoracic intrathecal injection of amitriptyline produced dose-dependent
      sedation but did not significantly affect spinal cord blood flow or hemodynamic
      variables. Spinal cord tissue concentrations of amitriptyline were 100 times
      greater in tissue near the tip of the thoracic intrathecal catheter compared with
      cervical cord tissue. Cerebrospinal fluid concentrations of catecholamines did
      not significantly change after amitriptyline was administered. Cervical
      intrathecal injection of 5 mg amitriptyline produced mild antinociception,
      whereas 10 mg produced intense sedation and, in one sheep, seizures and death.
      CONCLUSIONS: Although other preclinical toxicity studies are necessary before
      introducing intrathecal amitriptyline for use in humans, this study did not
      reveal dangerous changes in blood pressure or spinal cord blood flow from this
      agent.

PMID- 9158360
TI  - Calcium concentration-dependent mechanisms through which ketamine relaxes canine
      airway smooth muscle.
AB  - BACKGROUND: Ketamine is a potent bronchodilator that, in clinically used
      concentrations, relaxes airway smooth muscle in part by a direct effect. This
      study explored the role of calcium concentration (Ca2+) in this relaxation.
      METHODS: Canine trachea smooth muscle strips were loaded with the fluorescent
      probe fura-2 and mounted in a spectro-photometric system to measure force and
      intracellular calcium concentration ([Ca2+]i) simultaneously. Calcium influx was
      estimated using a manganese quenching technique. Cyclic nucleotides in the airway
      smooth muscle strips were measured by radioimmunoassay. RESULTS: In smooth muscle
      strips stimulated with submaximal (0.1 microM) and maximal (10 microM)
      concentrations of acetylcholine, ketamine caused a concentration-dependent
      decrease in force and [Ca2+]i. The sensitivity of the force response to ketamine
      significantly decreased as the intensity of muscarinic receptor stimulation
      increased; the median effective concentration for relaxation induced by ketamine
      was 59 microM and 850 microM for tissue contracted by 0.1 microM or 10 microM
      acetylcholine, respectively (P < 0.05). In contrast, the sensitivity of the
      [Ca2+]i response did not depend on the intensity of muscarinic receptor
      stimulation. Ketamine at 1 mM significantly inhibited calcium influx. Ketamine
      did not significantly increase cyclic nucleotide concentrations. CONCLUSIONS:
      Ketamine-induced relaxation of canine airway smooth muscle is associated with a
      decrease in [Ca2+]i and calcium influx, effects that are not mediated by an
      increase in cyclic nucleotides; and the sensitivity of the force response to
      ketamine decreases as the level of preexisting muscle tone increases, an effect
      that is not explained by differential effects on [Ca2+]i.

PMID- 9158362
TI  - Mild and moderate hypothermia provide better protection than a burst-suppression
      dose of thiopental against ischemic spinal cord injury in rabbits.
AB  - BACKGROUND: Controversy exists over the efficacy of different methods for
      protecting the spinal cord against experimental ischemic injury. Therefore, the
      authors compared the protective effects of thiopental with those of hypothermia
      (35 degrees C and 32 degrees C) on hindlimb motor functions and histopathology
      after transient spinal cord ischemia. METHODS: Twenty-seven New Zealand white
      rabbits were assigned to one of the four groups: a thiopental-normothermia group
      (burst-suppression dose of thiopental; esophageal temperature = 38 degrees C; n =
      7), a halothane-mild hypothermia group (halothane, 1%; esophageal temperature =
      35 degrees C; n = 7), a halothane-moderate hypothermia group (halothane, 1%;
      esophageal temperature = 32 degrees C; n = 6), and a halothane-normothermia group
      (halothane, 1%; esophageal temperature = 38 degrees C; n = 7). The animals were
      then subjected to 20 min of spinal cord ischemia produced by occlusion of the
      aorta distal to the origin of left renal artery. Hindlimb motor function was
      observed for 48 h after reperfusion. Histopathology of the lumbar spinal cord
      also was examined. RESULTS: All animals in the halothane-mild hypothermia and
      halothane-moderate hypothermia groups were neurologically normal 48 h after
      ischemia. There was no statistical difference in the final neurologic status and
      histopathology between the thiopental-normothermia and halothane-normothermia
      groups. However, the final neurologic status and histopathology in both groups
      were worse than in the halothane-mild hypothermia or halothane-moderate
      hypothermia groups. There was a strong correlation between the final neurologic
      status and the numbers of normal neurons in the anterior spinal cord.
      CONCLUSIONS: These results suggest that mild and moderate hypothermia protects
      against ischemic spinal cord injury in rabbits, and a burst-suppression dose of
      thiopental does not offer any advantage over halothane.

PMID- 9158361
TI  - Inhibition of lysophosphatidate signaling by lidocaine and bupivacaine.
AB  - BACKGROUND: Lidocaine and bupivacaine impair wound healing, but the mechanism of
      this side effect has not been determined. The phospholipid messenger
      lysophosphatidate is released from activated platelets and induces fibroblast and
      smooth muscle proliferation. Because it may play a role in wound healing, the
      authors studied the effects of local anesthetics on lysophosphatidate signaling
      in Xenopus oocytes. METHODS: Defolliculated Xenopus oocytes expressing endogenous
      G protein-coupled lysophosphatidate receptors were voltage clamped and studied in
      the presence or absence of lidocaine or bupivacaine. Lysophosphatidate-induced
      Ca(2+)-activated Cl- currents (IC1(Ca)) were measured. To determine the site of
      action of the local anesthetics on the signaling pathway, the authors studied 1)
      the effects of local anesthetics on signaling induced by intracellular injection
      of the second messenger inositoltrisphosphate, and 2) the effects of local
      anesthetics on functioning of recombinantly expressed angiotensin II receptor
      signaling through the same pathways as the lysophosphatidate receptor. RESULTS:
      Lysophosphatidate signaling was inhibited in the presence of local anesthetics.
      The half maximal inhibitory concentration (IC50S) for lidocaine and bupivacaine
      were 29.6 mM and 4.7 mM, respectively. Neither responses induced by
      inositoltrisphosphate injection nor angiotensin signaling were influenced by
      local anesthetics. CONCLUSIONS: Lysophosphatidate signaling is inhibited by the
      extracellular application of lidocaine or bupivacaine. In contrast,
      inositoltrisphosphate or angiotensin signaling was not affected by local
      anesthetics. Therefore local anesthetics have a specific, extracellular effect on
      lysophosphatidate receptor functioning. As the local anesthetic concentrations
      used were similar to those observed after injection around surgical wounds, LP
      inhibition may play a role in the observed detrimental effects of local
      anesthetics on wound healing.

PMID- 9158363
TI  - Role of adenosine in isoflurane-induced cardioprotection.
AB  - BACKGROUND: This investigation tested the hypothesis that adenosine (A1) receptor
      blockade modulates the cardioprotective effects of isoflurane. METHODS:
      Hemodynamics and percentage segment shortening (%SS) in the left anterior
      descending coronary artery (LAD) perfusion territory were evaluated in
      barbiturate-anesthetized dogs (n = 31) at selected intervals after pretreatment
      with the selective A1 receptor antagonist (8-cyclopentyl-1,3,dipropyl-xanthine;
      DPCPX 0.8 mg/kg, intravenously) or drug vehicle in the presence or absence of 1
      minimum alveolar concentration (MAC) isoflurane. Dogs were subjected to five 5
      min occlusions and reperfusions of the LAD, followed by 180 min of final
      reperfusion. Isoflurane was administered for 30 min before and during LAD
      occlusions and reperfusions and was discontinued at the onset of final
      reperfusion. Two other groups of dogs (n = 17) were used to measure interstitial
      concentrations of purines in the LAD region using a microdialysis technique in
      the presence and absence of isoflurane. RESULTS: Dogs receiving drug vehicle or
      DPCPX exhibited no recovery of %SS after 180 min of reperfusion (-5 +/- 7 and 5
      +/- 11% of baseline, respectively, +/- SEM). In contrast, dogs receiving
      isoflurane alone demonstrated complete recovery of %SS at 60 min after
      reperfusion. DPCPX pretreatment partially attenuated isoflurane-induced
      enhancement of recovery of %SS (34 +/- 11% of baseline 180 min after reperfusion;
      P < 0.05). Interstitial purine concentrations were increased during multiple
      occlusions and reperfusions of the LAD in dogs not receiving isoflurane, but they
      were unchanged by coronary artery occlusion and reperfusion in dogs receiving
      isoflurane. CONCLUSIONS: The results indicate that isoflurane-induced
      cardioprotection in stunned myocardium is partially mediated by adenosine type 1
      receptor activation and is accompanied by decreases in endogenous adenosine
      release.

PMID- 9158364
TI  - Tracheal mucus velocity remains normal in healthy sheep intubated with a new
      endotracheal tube with a novel laryngeal seal.
AB  - BACKGROUND: Tracheal mucus velocity (TMV), an index of mucociliary clearance, is
      reduced markedly in patients intubated with standard endotracheal tubes (ETTs)
      with high-compliance low-pressure (hi-lo) cuffs. The authors developed a new
      ultra-thin walled ETT in which the inflatable cuff is replaced with a no-pressure
      seal, positioned at the level of the larynx. The seal consists of 12 to 20
      toroidal layers of thin polyurethane film ("gills") at the level of the vocal
      cords and prevents both air leak and fluid aspiration. The authors hypothesized
      that ETTs with the new laryngeal seal may impair TMV less than ETTs with inflated
      hi-lo cuffs do. METHODS: The TMV was measured in seven healthy female sheep by
      radiographically tracking the motion of small discs of tantalum inserted into the
      trachea through a bronchoscope. The TMV was measured in spontaneously breathing
      sheep before intubation (baseline) and after intubation with either a hi-lo ETT
      (control group) or after intubation with a new ETT with gills (study group). Four
      to six weeks later, the studies were repeated, but the sheep that were previously
      in the control group served as the study group, and those in the study group
      served as controls. RESULTS: Baseline TMV did not differ in the two groups. In
      the control group, TMV decreased significantly (by 67%) from baseline. In the
      study group, TMV did not differ significantly from baseline and remained steady
      during 3 h of intubation. CONCLUSIONS: The TMV does not change in sheep intubated
      with new ETTs with gills. The new ETT's may help promote a normal mucociliary
      clearance in patients who require ventilation.

PMID- 9158365
TI  - The successful implementation of pharmaceutical practice guidelines. Analysis of
      associated outcomes and cost savings. SWiPE Group. Systematic Withdrawal of
      Perioperative Expenses.
AB  - BACKGROUND: Although approximately 2,000 medical practice guidelines have been
      proposed, few have been successfully implemented and sustained. We hypothesized
      that we could develop and institute practice guidelines to promote more
      appropriate use of costly anesthetics, to generate and sustain widespread
      compliance from a large physician group, and to decrease costs without adversely
      affecting clinical outcomes. METHODS: A prospective before and after comparison
      study was performed at a tertiary care medical center. Clinical outcomes data and
      times indicative of perioperative patient flow were collected on the first of two
      sets of patients 1 month before discussion of practice guidelines. Practice
      guidelines were developed by the physicians and their associated care team for
      the intraoperative use of anesthetic drugs. A drug distribution process was
      developed to aid compliance. Clinical outcomes data and times indicative of
      perioperative patient flow were collected on the second set of patients 1 month
      after institution of practice guidelines. Hospital drug costs and adherence to
      guidelines were noted throughout the study period and for each of the following 9
      months by querying the database of an automated anesthesia record keeper.
      RESULTS: A total of 1,744 patients were studied. Drug costs decreased from 56
      dollars per case to 32 dollars per case as a result of adherence to practice
      guidelines. Perioperative patient flow was minimally affected. Time (mean +/- SD)
      from end of surgery to arrival in the post-anesthesia care unit (PACU) increased
      from 11 +/- 7 min before the authors instituted practice guidelines to 14 +/- 8
      min after practice guidelines (P < 0.0001). Admission of inpatients to the PACU
      receiving monitored anesthesia care increased from 6.5 to 12.9% (P < 0.02).
      Perioperative patient flow and clinical outcomes were not otherwise adversely
      affected. Compliance and cost savings have been sustained. CONCLUSIONS: This
      study is an example of a successful physician-directed program to promote more
      appropriate utilization of health care resources. Cost savings were obtained
      without any substantial changes in clinical outcomes. Institution of similar
      practice guidelines should result in pharmaceutical savings in the range of 50%
      at tertiary care centers around the country, with a slightly smaller degree of
      savings expected at institutions with more ambulatory surgery.

PMID- 9158366
TI  - Using an anesthesia information management system as a cost containment tool.
      Description and validation.
AB  - BACKGROUND: Medical informatics provide a new way to evaluate the practice of
      medicine. Anesthesia automated record keepers have introduced anesthesiologists
      to computerized medical records. To derive useful information from the stored
      data requires programming that is not currently commercially available. The
      authors describe how they custom-programmed an automated record keeper's database
      to perform cost calculations, how they validated the programming, and how they
      used the data in a successful pharmaceutical cost-containment program. METHODS:
      The Arkive (San Diego, CA) automated record keeper database was programmed at
      Duke University Medical Center as an independent noncommercial project to
      calculate costs according to standard formulae and to follow adherence to Duke
      University Department of Anesthesiology's prescribing guidelines for anesthetic
      drugs. Validation of that programming (including analysis of discarded drugs) was
      accomplished by comparing database calculated costs with actual pharmacy
      distribution of drugs during a 1-month period. RESULTS: Validation data
      demonstrated a 99% accuracy rate for total costs of the drugs studied
      (atracurium, vecuronium, rocuronium, propofol, midazolam, fentanyl, and
      isoflurane). The study drugs represented approximately 67% of all drug costs for
      the period studied. CONCLUSIONS: Programming of an anesthesia automated record
      keeper's database yields essential information for management of an anesthetic
      practice. Accurate economic evaluation of anesthetic drug use is now possible. In
      the future, as definitive identification of best anesthetic practices that yield
      optimal patient outcomes and higher measures of patient satisfaction is pursued,
      large numbers of patients should be studied. This is only possible through
      database analysis and complete computerization of the perioperative medical
      record.

PMID- 9158367
TI  - Economics of anesthetic practice.
AB  - Anesthesiologists, like all other specialists, need to examine carefully their
      clinical practices so that excessive costs and waste can be reduced without
      compromising patient care or safety. While costs of drugs used for anesthesia
      constitute only a small fraction of total health care cost, they are highly
      visible costs which are easy for administrators to scrutinize. Although cost
      savings in an individual case may be small, the total savings may be impressive
      because of the large volume of cases performed. In a recent analysis of
      strategies to decrease PACU costs, Dexter and Tinker found that anesthesiologists
      have "little control over PACU economics via the choice of anesthetic drugs".
      Greater savings could be achieved by timing the arrival of patients into the PACU
      to reduce the peak requirement of nursing personnel. Hospital and operating room
      management would be better served by concentrating on these simple measures to
      improve efficiency rather than forcing anesthesiologists to base drug usage on
      acquisition costs. Even in countries that have nationalized health services,
      salaries make up the largest part of the costs, and the expenses in delaying an
      operation by 30 min exceeds the costs of a 2 h propofol infusion. It is becoming
      increasingly apparent that attempts at better scheduling of cases, more efficient
      processing of patients in the PACU to optimize admission rates, and reduced
      wastage of anesthetic and surgical supplies lead to greater savings than reducing
      anesthetic-related drug costs. Nevertheless, it is still important for
      anesthesiologists to participate in the ongoing effort to reduce medical costs
      without affecting the quality of patient care. Quality care and fiscally sound
      decision-making are not necessarily mutually exclusive. Simple, effective cost
      containment measures that all anesthesiologists can practice include using low
      fresh gas flow rates with inhalation agents and opening sterile packages and drug
      ampules only if the contents will be used. The choice of an anesthetic agent for
      routine use depends not only on its demonstrated efficacy and side effect
      profile, but also on economic factors. It is important to perform careful
      pharmacoeconomic evaluations of these newer drugs, including assessing all
      associated costs and benefits for subsets of patients undergoing different types
      of surgical procedures. These evaluations should also include input from patients
      regarding their personal preferences. Excessive emphasis on the acquisition costs
      of drugs may lead to blanket bans on the use of new drugs because of their higher
      costs rather than permitting physicians to individualize therapy according to
      their clinical experience and the perceived needs of a given patient.
      Institutional and individual variations in clinical practices, their associated
      costs and outcomes may alter conclusions about acceptability and economic
      evaluation of a particular drug or technique. The information in this review can
      be used to provide a rational basis for incorporating cost considerations into
      the decision-making process regarding the drugs, devices and techniques used in
      anesthesiology.

PMID- 9158368
TI  - Principles of economic analysis.

PMID- 9158369
TI  - Dyclonine hydrochloride for airway anesthesia: awake endotracheal intubation in a
      patient with suspected local anesthetic allergy.

PMID- 9158370
TI  - Warm air convection heating blankets may increase the absorption of transdermal
      nitroglycerin.

PMID- 9158371
TI  - Temporary right coronary artery flow disruption during instrumented correction of
      the spine.

PMID- 9158372
TI  - Adverse reactions to nonindicated medications.

PMID- 9158373
TI  - An alternative needle geometry for interruption of the ganglion impar.

PMID- 9158374
TI  - Breaking glass vials.

PMID- 9158375
TI  - Residual postoperative paralysis. Yes, it does matter.

PMID- 9158376
TI  - Mini flashlight as a spare light source for a failing fiberoptic laryngoscope.

PMID- 9158377
TI  - A method for removing the laryngeal mask airway after using it as an intubation
      guide.

PMID- 9158378
TI  - External leg compression in the treatment of vascular disease.
AB  - In summary, external compression of the limbs is a mode of therapy that has
      enjoyed a long history in the treatment of venous and arterial disease. Evidence
      suggests that its beneficial effects are mediated through enhancement of venous
      and arterial blood flow, promotion of vasodilation, enhancement of fibrinolysis,
      and, in the case of obstructive arterial disease, promotion of the development of
      collateral circulation. The utility of external leg compression in the prevention
      of deep venous thrombosis and in the management of chronic venous stasis disease
      has been well documented, and it has become an accepted treatment for these
      disorders. The use of pneumatic compression in the treatment of atherosclerotic
      peripheral vascular and cardiovascular disease is less widespread and its
      indications are less well defined. Though the work of a few investigators in each
      of these areas shows striking benefits of the technique, further investigation in
      these areas is warranted. Potential benefits to patients of external limb
      compression therapy include its non-invasive nature, its ability to be applied in
      an out-patient setting, and long-term cost savings through possible avoidance of
      hospitalization and invasive procedures.

PMID- 9158379
TI  - Fifteen years of experience in treating 2177 episodes of foot and leg lesions
      with the circulator boot. Results of treatments with the circulator boot.
AB  - OBJECTIVE: To determine the clinical effectiveness of the end-diastolic pneumatic
      compression boot and of local antibiotics in treating limb lesions associated
      with diabetes and peripheral arterial, venous, and neuropathic disease. RESEARCH
      DESIGN AND METHODS: Office and hospital data were kept over 15 years on 2177
      episodes of leg problems classified by the Wagner method for 1514 legs of 1035
      patients largely referred because of failure of standard therapies. The fate of
      the untreated legs served as a controls when possible. RESULTS: Healing or
      improvement of treated legs was seen above that in the literature in all Wagner
      categories and was significant (P < 0.001) compared to the "control" leg, which
      deteriorated in 38.7% of patients. Significant risk factors against a successful
      outcome included smoking, inability to walk, increased home distance from the
      boot center, loss to treatment, hemodialysis, a Wagner 4-5 classification,
      inoperable iliac occlusions, vascular procedures before or after referral for
      boot therapy, and an aggressive vascular surgeon. Neuropathy allowed successful
      treatment of lesions nondiabetic patients could not tolerate. Relapse was
      significantly more frequent in arteriosclerosis obliterans (ASO) patients with
      diabetes than without diabetes and in patients with neuropathy than in those with
      ASO. Diabetes did not affect the relapse rate in stasis disease. The overall
      percentage of legs having major amputations was low: 2.5% for diabetic legs at
      the initial treatment episode, 1.6% at the time of a relapse, and 4.1% after
      seeking treatment elsewhere. For nondiabetic patients, the respective risks were
      similar: 2.0%, 1.2%, and 2.9%.

PMID- 9158380
TI  - Patient assessment and examples of a method of treatment. Use of the circulator
      boot in peripheral vascular disease.
AB  - Effective peripheral blood flow is positively related to cardiac output and
      gravity (part dependent) and inversely related to gravity (part elevated), venous
      pressure, interstitial fluid pressure, degree of peripheral neuropathy,
      arteriosclerotic and thrombotic arterial obstructions, and infection. These
      factors are considered in the operation of the end-diastolic pneumatic boot in
      the treatment of illustrative patients with lymphedema, venous stasis disease,
      peripheral arteriosclerosis obliterans, peripheral neuropathy, cellulitis, and
      osteomyelitis and the failing heart. A method of treatment that includes the use
      of the boot and the injection of local antibiotics is described.

PMID- 9158381
TI  - Clinical manifestations of Takayasu arteritis in India and Japan--new
      classification of angiographic findings.
AB  - In this retrospective review 102 Indian and 80 Japanese patients with Takayasu
      arteritis were compared in regard to their clinical manifestations and
      angiographic findings. Regardless of nationality, most patients were initially
      affected in their teens or twenties. Japanese patients were female in a larger
      ratio compared with the ratio in India. Clinically, the two groups exhibited
      several different features. More Japanese patients were found to be pulseless (P
      < 0.01) whereas many Indian patients were hypertensive (P < 0.01). Inflammatory
      conditions in Japanese patients were more severe (P < 0.01) and tended to be more
      prolonged than those in the Indians. More Japanese patients suffered from aortic
      regurgitation (P < 0.01), but Indians suffered from hypertension (P < 0.01).
      Angiographic findings revealed that the aortic arch and its branches were mainly
      involved in Japanese patients (type I, IIa) whereas the abdominal aorta and its
      branches were mainly involved in Indian patients (type IV). However, the
      diffusely involved type (type V) was the one most commonly found in both
      countries. From the analyses of vascular lesions in both Indian and Japanese
      patients, 510 and 396, respectively, different progressions of vasculitis are
      speculated. In Japanese patients, vasculitis generally occurs in the ascending
      aorta, the aortic arch, and/or its branches and extends into the thoracic and
      abdominal aorta, subsequently forming various complicated lesions with prolonged
      inflammatory activity. On the other hand, in Indian patients, vasculitis
      generally occurs in the abdominal aorta involving renal arteries, subsequently
      extending into the thoracic aorta within one or two decades, simple vascular
      lesions being formed. Data analysis suggests that this morbid condition
      progresses differently in India and Japan, in spite of some common etiologic
      factor(s).

PMID- 9158382
TI  - Immunohistochemical and ultrastructural examination of smooth muscle cells in
      aortocoronary saphenous vein grafts.
AB  - In this study, phenotypic modulation and remodulation of smooth muscle cells and
      associated intermediate filament expression were demonstrated by means of
      immunohistochemistry and ultrastructure to understand the development of intimal
      hyperplasia in aortocoronary saphenous vein grafts. In nongrafted saphenous
      veins, all smooth muscle cells expressed vimentin and desmin and were of a
      contractile form. In saphenous vein grafts showing stenotic intimal hyperplasia
      (luminal stenosis < 75%), expression of desmin was notably lower, whereas that of
      vimentin was higher. The cells were shown to be of a synthetic phenotype,
      suggesting modulation from the original contractile form. In saphenous vein
      grafts showing occlusive intimal hyperplasia (luminal stenosis > 76%), desmin
      expression in smooth muscle cells was increased again, and such cells were of a
      contractile form, suggesting remodulation from the synthetic phenotype. Some of
      the smooth muscle cells of the synthetic phenotype were positive for an antibody
      against proliferation cell nuclear antigen. Smooth muscle cells of the
      contractile form were negative for this antibody. The study suggests that smooth
      muscle cells of synthetic phenotype are highly responsible for "growing" intimal
      hyperplasia of aortocoronary saphenous vein grafts.

PMID- 9158384
TI  - Comparative effects of volume loading on pulmonary venous flow in dogs with
      normal heart and with myocardial ischemia.
AB  - The influences of cardiac loading conditions and left ventricular performance on
      pulmonary venous flow are poorly understood. The authors studied the effects of
      volume loading on the pattern of pulmonary venous flow in normal and ischemic
      hearts. Thirteen anesthetized dogs were equipped with a transit-time ultrasonic
      flow probe around the left upper pulmonary vein. In 6 of the dogs, the left
      anterior descending artery was ligated to induce myocardial ischemia. The
      remaining 7 dogs had normal hearts. Heart rate was fixed at 110 beats/minute by
      right atrial pacing. Dextran was infused from the femoral vein until mean left
      atrial pressure increased 3 mm Hg above the baseline value in both groups. In
      normal heart, systolic pulmonary venous flow volume (SI) increased significantly,
      but early diastolic flow volume (DI) did not show a significant change during
      volume loading. The ratio of SI/DI increased significantly (1.12 +/- 0.34 vs 2.11
      +/- 0.49, P < 0.05). After ligation of the left anterior descending artery, the
      SI and DI decreased significantly. The ratio of SI/DI did not show a significant
      change (0.88 +/- 0.32 vs 0.87 +/- 0.30, ns). In dogs with myocardial ischemia,
      volume loading caused increases in the SI and DI. However, no significant change
      was observed in the ratio of SI/DI (0.87 +/- 0.30 vs 0.97 +/- 0.36, ns). These
      findings demonstrate that left ventricular performance influences the alteration
      in pulmonary venous flow pattern that is caused by systemic volume loading.

PMID- 9158383
TI  - Effects of oral administration of purified micronized flavonoid fraction on
      increased microvascular permeability induced by various agents and on
      ischemia/reperfusion in the hamster cheek pouch.
AB  - The effects of a clinically used purified micronized flavonoid fraction (S 5682)
      containing 90% diosmin and 10% hesperidin on increased microvascular permeability
      induced by histamine, bradykinin, and leukotriene B4 (LTB4) were investigated by
      intravital microscopy in the hamster cheek pouch preparation. The authors also
      investigated the effects of S 5682 on macromolecular permeability increase and
      leukocyte adhesion during ischemia-reperfusion by using the same preparation. S
      5682, suspended in 10% lactose solution, or vehicle (10% lactose) was
      administered orally to male hamsters for ten days at 20 mg/kg/day (10 mg/kg twice
      a day). Fluorescein isothiocyanate (FITC)-labeled dextran (mol wt 150,000) was
      given intravenously, thirty minutes after completion of the cheek pouch
      preparation. The leukocytes were stained by continuous IV infusion of acridine
      orange (0.5 mg/kg/minute). Histamine (2 microM), bradykinin (1 microM), and LTB4
      (0.01 microM), applied topically for five minutes, increased the number of
      fluorescent vascular leakage sites in postcapillary venules. A temporary ischemia
      with total circulatory arrest of the cheek pouch was obtained by clamping the
      neck of the everted pouch. The maximum number of leaky sites (per cm2 in the
      prepared area) that occurred either at five minutes after the beginning of each
      topical application or ten minutes after the onset of reperfusion was quantified
      in ultraviolet light microscopy. The results from 60 animals divided into 10
      groups of 6 animals each are presented as means +/- SEM. In comparison with
      vehicle, S 5682 significantly inhibited the macromolecular permeability
      increasing effect of histamine (343.5 +/- 22.3 versus 207.5 +/- 32.0 leaks/cm2; P
      < 0.01), bradykinin (345.2 +/- 19.0 versus 206.2 +/- 21.6 leaks/cm2; P < 0.01),
      and LTB4 (353.3 +/- 27.5 versus 242.7 +/- 33.6 leaks/cm2; P < 0.05). At
      reperfusion, after thirty minutes of ischemia, S 5682 significantly decreased the
      observed macromolecular permeability (103.6 +/- 15.4 versus 42.6 +/- 9.3
      leaks/cm2; P < 0.01). Flavonoid-treated animals also displayed a statistically
      significant lower number of adhering leukocytes to the venular endothelium (83.5
      +/- 9.5 versus 48.4 +/- 12.3 per 6 mm2; P < 0.05). These results demonstrate that
      oral administration of S 5682 for ten days at 20 mg/kg body weight/day had a
      protective effect against leakage of macromolecules after application of
      permeability-increasing substances and during ischemia-reperfusion in the cheek
      pouch microvasculature. Since firm leukocyte attachment to the endothelial wall
      and subsequent emigration of leukocytes into the interstitium is a mechanism for
      tissue damage during inflammation, attenuation of this phenomenon during
      conditions of ischemia-reperfusion can in part explain previous observations that
      this purified micronized flavonoid fraction decreases edema formation. The
      present data illustrating the inhibitory effect of a clinically relevant dose of
      S 5682 on the inflammatory processes induced in this in vivo model of
      microcirculation may serve as a rational basis to explain its clinical efficacy.

PMID- 9158385
TI  - Effects of trimetazidine on heart rate variability and left ventricular systolic
      performance in patients with coronary artery disease after percutaneous
      transluminal angioplasty.
AB  - Fifty-one patients (mean age 51.6 +/- 7.1 years) with angiographically proven
      coronary artery disease (CAD) entered the study. In 26 patients (Group I),
      trimetazidine treatment started twenty-four hours after percutaneous transluminal
      coronary angioplasty (PTCA). Another 25 patients (Group II) without trimetazidine
      treatment were kept as controls. The groups were comparable by age, gender, risk
      factors of CAD, coronary anatomy, left ventricular performance, and heart rate
      variability indices at baseline state. Power spectral analysis of heart rate
      variability and two-dimensional and Doppler echocardiographic examinations were
      performed before PTCA, and twenty-four hours, ten days, thirty days, and three
      months after PTCA. A statistically significant improvement of left ventricular
      systolic performance (P < 0.001), augmentation of the parasympathetic band of
      heart rate variability (P < 0.001), and decline of P1/P2 ratio (P < 0.01) were
      evident in patients treated with trimetazidine, while no apparent changes were
      observed in controls. The intergroup analysis also showed marked difference
      between groups as recorded on the day 30 and month 3 of observation (P < 0.001).
      During follow-up period recurrences of angina pectoris and ischemia were
      registered in Group II, while no evidence of ischemia was discerned in Group I
      patients. In conclusion, trimetazidine modulates the autonomic control of heart
      rate, ie, reduces sympathetic overactivity and augments vagal influences,
      improves left ventricular contractility, and diminishes the clinical
      manifestations of ischemia in patients with CAD after PTCA.

PMID- 9158387
TI  - Continuous retrograde cardiac perfusion decreases risk of reoperative coronary
      artery bypass grafting.
AB  - Embolization of atheromatous debris from old saphenous vein grafts is a major
      factor that increases the risk of reoperative coronary artery bypass grafting
      (CABG) when compared with primary CABG. To decrease this risk, a technique
      consisting of minimal dissection of the heart prior to cross clamping, continuous
      retrograde coronary sinus perfusion with 32 degrees C blood, and temporary
      posterior cardiac interventricular vein occlusion, during which time all
      dissection and anastomoses are performed, was evaluated prospectively in 130
      consecutive patients from January 2, 1991, through February 28, 1995. This group
      was compared with a cohort of 1107 patients undergoing primary CABG performed
      concurrently. The two groups were similar in age (median sixty-eight years),
      incidence of hypercholesterolemia, peripheral vascular disease, smoking history,
      and left main stem stenosis. More patients undergoing reoperative CABG had
      previous myocardial infarctions (61.5% vs 54.5%), a higher incidence of triple
      vessel coronary artery disease (89.2% vs 77.1%, P = 0.002), and a lower ejection
      fraction (54.0% vs 56.9%). The median interval from primary CABG to reoperative
      CABG was one hundred twenty-seven months with a range of 2.5 to two hundred
      seventy-nine months. The cross clamp time (median one hundred three vs sixty-nine
      minutes, P = 0.000001) and perfusion time (median one hundred thirty-four vs
      ninety-four minutes, P = 0.000001) were significantly higher in the reoperative
      CABG group. The requirements for inotropic support postoperatively, perioperative
      myocardial infarction (1.5% vs 2.4%, P = 0.397), and mortality (3.1% vs 3.4%, P =
      0.54) were statistically equivalent in the two groups. These data reveal that
      continuous retrograde coronary sinus perfusion, posterior cardiac
      interventricular vein occlusion, and single cross-clamping technique improve
      outcomes of reoperative CABG to that approaching primary CABG.

PMID- 9158386
TI  - Cardiac trauma. Diagnosis, management, and current therapy.
AB  - In cardiac trauma the two main mechanisms of injury are blunt and penetrating
      trauma. Common cardiac effects of trauma include myocardial rupture, contusion,
      laceration, pericardial insult, coronary injury, valvular damage, arrhythmias,
      and conduction abnormalities. Hemodynamic instability can develop rapidly and
      pose marked risk to patient survival. An adequate level of clinical awareness and
      timely use of diagnostic techniques such as echocardiography, aortography, and
      cardiac angiography are essential for rapid identification of cardiac trauma.
      Once the diagnosis is made, prompt surgical intervention is often the key to
      survival.

PMID- 9158388
TI  - Percutaneous transvenous mitral balloon valvuloplasty alone in patients with
      combined aortic and mitral stenosis.
AB  - To investigate the feasibility of percutaneous transvenous balloon dilatation of
      the mitral valve in patients with combined aortic and mitral stenosis, 12
      patients were studied by echocardiography and catheterization before and after
      mitral valvuloplasty. Aortic stenosis was defined from prevalvuloplasty
      catheterization study as a transaortic pressure gradient of more than 25 mm Hg.
      All 12 patients underwent transvenous balloon mitral valvuloplasty successfully.
      Immediately after the procedure, all patients experienced improvement in clinical
      symptoms and in hemodynamic variables. Mitral valve areas were significantly
      increased from 0.78 +/- 0.18 to 1.73 +/- 0.21 cm2 (P < 0.0001) by planimetry
      method. Cardiac output was significantly increased from 3.6 +/- 0.1 to 4.2 +/-
      0.5 L/min (P = 0.01). Mean transaortic flow rate increased 33% (from 198 +/- 68
      to 254 +/- 41 mL/s, P = 0.002). Mean pressure gradient across the aortic valve
      after mitral valvuloplasty was not significantly increased, from 34 +/- 7 to 37
      +/- 13 mm Hg. Aortic valve areas, derived from the Gorlin formula, were
      significantly increased from 0.57 +/- 0.12 to 0.73 +/- 0.14 cm2 (P = 0.006) after
      mitral valvuloplasty. However, continuity equation-derived aortic valve area was
      independent of increasing flow rate after mitral valvuloplasty from 1.29 +/- 0.35
      to 1.30 +/- 0.29 cm2. During follow-up with a mean of twenty four +/- fourteen
      months, 8 patients were in New York Heart association functional class I, 3 in
      class II, and 1 in class IV who received pericardiotomy owing to constrictive
      pericarditis without aortic valve replacement. In conclusion, mitral
      valvuloplasty alone may be safe and effective in alleviating symptoms in mitral
      stenosis patients with transaortic pressure gradient > 25 mm Hg. Continuity
      equation-derived aortic valve areas seem to be flow independent in evaluation of
      aortic stenosis and are important for decision making.

PMID- 9158389
TI  - Percutaneous transluminal coronary angioplasty for morphologic left anterior
      descending artery lesion in a patient with dextrocardia. A case report and
      literature review.
AB  - A case report of percutaneous transluminal coronary angioplasty (PTCA) to treat
      coronary atherosclerotic lesions in a patient with dextrocardia associated with
      situs inversus totalis is presented. The patient was a sixty-two-year-old man who
      was admitted with a diagnosis of congestive heart failure. Cardiac
      catheterization was performed. Left ventriculography showed mild hypokinesis in
      segments 2 and 3 with ejection fraction of 63%. Coronary arteriography revealed
      74% stenosis in segment 7 of the left anterior descending (LAD) artery. PTCA for
      this lesion was performed. Successful dilation was achieved with the residual
      stenosis in the LAD reduced from 74% to 34%. Performance of PTCA in patients with
      dextrocardia is extremely rare, and only 8 cases have been reported to date.
      However, by visualizing the procedure as a mirror image and choosing a guide
      catheter that permits good engagement, it appears possible to perform it like
      ordinary PTCA.

PMID- 9158390
TI  - Successful treatment of intermittent claudication due to spinal canal stenosis
      using beraprost sodium, a stable prostaglandin I2 analogue. A case report.
AB  - The syndrome of intermittent claudication can be induced not only by vascular
      insufficiency of the lower limbs but also by diseases of the spinal cord and
      cauda equina. The authors describe a sixty-year-old man with intermittent
      claudication due to spinal canal stenosis who was successfully treated with
      beraprost sodium, a stable prostaglandin I2 analogue. This drug has a long
      biological half-life and is orally effective in vasodilation, which is suggested
      to be beneficial in treating this syndrome. Beraprost sodium may become one of
      the major drugs for conservative therapy of intermittent claudication induced by
      spinal canal stenosis.

PMID- 9158391
TI  - Percutaneous balloon valvuloplasty for severe mitral stenosis in pregnancy. Four
      case reports.
AB  - Four pregnant women with mitral stenosis who did not respond to medical therapy
      underwent successful percutaneous balloon valvuloplasty with complete resolution
      of their symptoms. Their clinical features and echocardial and hemodynamic data
      are presented. The procedures and the remainder of their pregnancy were
      uncomplicated. Percutaneous balloon valvuloplasty of the mitral valve is a safe
      and effective alternative to surgical therapy if medical management is
      unsuccessful.

PMID- 9158392
TI  - Management of bilateral glottic tumors.
AB  - OBJECTIVE: To compare the rates of cure and complication and the time to
      decannulation and deglutition in patients undergoing resection of bilateral
      glottic tumors. DESIGN: A 22-year, nonrandomized, prospective, retrospective
      analysis. SETTING: Two academic tertiary care referral centers. PARTICIPANTS:
      Seventy-two patients with bilateral glottic carcinoma were treated using
      bilateral hemilaryngectomy. Depending on the size of the tumor and the extent of
      thyroid cartilage resection, patients underwent 1 of 3 methods of reconstruction:
      group 1, placement of an anterior commissure stent (34 patients); group 2,
      epiglottic laryngoplasty (15 patients); and group 3, staged posterior thyroid
      alar transposition laryngoplasty (23 patients). INTERVENTION: Resection and
      reconstruction of 72 larynges with bilateral glottic tumors using the bilateral
      hemilaryngectomy procedures. MAIN OUTCOME MEASURES: Acceptable rates of cure and
      complication, intervals to decannulation and deglutition, and quality of speech.
      RESULTS: High rates of tumor control and cure, low rates of recurrence and
      complication, acceptable time to decannulation and deglutition, and adequate
      quality and intelligibility of speech. CONCLUSIONS: Bilateral vocal cord
      carcinoma can be treated surgically with a high degree of tumor control and cure.
      The use of all 3 methods maintained laryngeal function with regard to tracheal
      decannulation, oral alimentation, and speech intelligibility.

PMID- 9158393
TI  - Patterns of care for cancer of the larynx in the United States.
AB  - OBJECTIVE: To assess case-mix characteristics, treatment patterns, and outcomes
      for laryngeal cancer using the largest series of patients to date. DESIGN:
      Analyses performed on retrospectively collected survey data submitted by
      hospitals for diagnostic periods 1980 through 1985 and 1990 through 1992 (with a
      9-year follow-up for the long-term group). SETTING: Broad spectrum of US
      hospitals (N = 769). PATIENTS: Consecutively accrued series of patients with
      laryngeal cancer (N = 16,936), with only squamous cell carcinomas (N = 16,213)
      analyzed. INTERVENTIONS: Surgery, radiation therapy, and chemotherapy. MAIN
      OUTCOME MEASURES: Descriptive analyses of case-mix, diagnostic, and treatment
      characteristics plus recurrence and 5-year, disease-specific survival outcomes.
      RESULTS: There was a slight increase across these years in stage IV disease and
      in radiation therapy (with or without surgery and/or chemotherapy). Overall
      diversity of management of this disease (by site and stage) was apparent. Five
      year survival rates indicated a large difference between modified groupings of
      the T and N classifications, separating stages III and IV cases into localized
      disease (87.5% for T1-T2; 76.0% for T3-T4 cases) and regional metastasis (46.2%).
      CONCLUSIONS: Regardless of improvements in entering data in hospital records
      (most commendably, staging), more rigorous standards are needed. Also, the small
      increase in advanced-stage patients indicates that efforts toward early detection
      have not been successful. The rise in radiation therapy perhaps reflected an
      increased use of nonsurgical treatment for early-stage patients and organ-sparing
      radiochemotherapy protocols for advanced-stage patients. Regrouping stages III
      and IV cases into localized disease vs regional metastasis appears to predict
      survival better. Ongoing refinements of the American Joint Committee on Cancer
      staging scheme will hopefully improve this cancer's classification.

PMID- 9158394
TI  - The surgical management of laryngotracheal invasion by well-differentiated
      papillary thyroid carcinoma.
AB  - OBJECTIVES: To determine prognostic factors for survival in patients with
      invasive well-differentiated thyroid carcinoma, specifically examining
      laryngotracheal invasion as an independent prognostic factor, and to compare
      types of surgical resection to determine treatment efficacy. DESIGN:
      Retrospective review of patients with papillary invasive well-differentiated
      thyroid carcinoma surgically treated over 45 years. SETTING: Academic tertiary
      care medical center. PATIENTS: A total of 292 patients with invasive well
      differentiated thyroid carcinoma were surgically treated between 1940 and 1995.
      Informed consent was obtained from all patients. Extent and location of tumor
      invasion were determined. Invasion of larynx and/or trachea occurred in 124
      patients (41%). Patterns of invasion and techniques of surgical resection were
      evaluated. INTERVENTION: Types of surgical resection performed: complete tumor
      removal (n = 34), "shave" excision (n = 75), and incomplete tumor excision (n =
      15). MAIN OUTCOME MEASURES: Cox regression analysis was used to determine
      significance of prognostic factors for survival; Kaplan-Meier curves were used to
      evaluate survival. A P value of less than .05 was statistically significant.
      RESULTS: Patterns of invasion by thyroid carcinoma included direct spread through
      laryngeal framework into paraglottic space or spread from involved lymph nodes.
      Laryngotracheal invasion was a significant, independent, prognostic factor for
      survival (P < .05). Significance was reached when types of resection were
      compared for all patients (P < .05) as well as for those with laryngotracheal
      invasion alone (P < .001). CONCLUSIONS: Laryngotracheal invasion was a
      significant independent prognostic factor for survival (P < .05). When types of
      surgical resection were compared, the survival rates of patients who underwent
      shave excision were not different from those of patients who underwent radical
      tumor resection if gross tumor did not remain (P > .05). Tumors with minimal
      invasion may be treated by shaving tumor from the aerodigestive tract. Gross
      intraluminal involvement should be resected completely to prevent complications.

PMID- 9158395
TI  - Communication after laryngectomy. An assessment of patient satisfaction.
AB  - OBJECTIVES: To determine the satisfaction of patients with their current method
      of alaryngeal communication. To focus primarily on the patients' perception of
      their own speech. DESIGN: A retrospective review of patients who underwent total
      laryngectomy for malignancy identified 4 groups of patients. A survey using a
      mailed questionnaire was used to compare groups. SETTING: Tertiary care
      university hospital, University of Texas Medical Branch at Galveston. PATIENTS:
      Forty-seven patients underwent total laryngectomy for cancer and survived. Thirty
      one of the 47 patients responded to the survey. Patients were divided into 4
      groups by their current method of communication: (1) tablet writers; (2)
      esophageal speech; (3) electrolarynx; and (4) tracheoesophageal speech. MAIN
      OUTCOME MEASURES: Satisfaction with communication, satisfaction with speech
      quality, ability to communicate over telephone, limitation of interaction with
      others, and satisfaction with quality of life. RESULTS: Patients in group 4 were
      significantly more satisfied with their speech (P < .001), perceived their speech
      to be of better quality (P < .001), had improved ability to communicate over the
      telephone (P < .001), and had less limitation of their interactions with others
      (P < .004). Patients in group 4 also rated their overall quality of life higher
      (P = .23). CONCLUSION: Although many studies in the past have demonstrated the
      objective superiority of tracheoesophageal speech compared with other methods of
      alaryngeal communication, most studies have focused on the intelligibility of
      speech judged by listeners. This study demonstrates that patients who use
      tracheoesophageal speech rate their own speech significantly higher than patients
      who use other methods and most likely have an overall superior quality of life.

PMID- 9158396
TI  - Overexpression of cyclin D1 indicates a poor prognosis in squamous cell carcinoma
      of the head and neck.
AB  - OBJECTIVES: To evaluate the overexpression of cyclin D1 and p53 as a prognostic
      marker of squamous cell carcinoma of the head and neck and to investigate whether
      deregulation of these genes is associated with an unfavorable course of disease.
      DESIGN: Retrospective study. MATERIALS AND METHODS: Formalin-fixed, paraffin
      embedded tumor materials that were obtained from a well-characterized series of
      115 patients with resectable head and neck cancer at The Netherlands Cancer
      Institute, Amsterdam, were analyzed by immunohistochemical methods using
      antiserum samples that were directed against 2 proteins (ie, cyclin D1 and p53),
      which are crucial in the regulation of the G1 phase of the cell cycle. RESULTS:
      Overexpression of cyclin D1 protein was found in 49% of the patients with
      squamous cell carcinoma of the head and neck. This overexpression was not
      associated with known prognostic factors (eg, the T and N stages). Tumors
      recurred more frequently and in a shorter period in patients whose primary tumors
      showed an overexpression of cyclin D1 protein. This difference (P = .05) was
      statistically significant in a stepwise proportional hazard regression analysis.
      However, since a discrepancy in staining results was observed between the biopsy
      and resection materials that were taken from the same patient, this result may
      not have been applicable in the evaluation of biopsy specimens only. This
      discrepancy is most likely owing to tissue heterogeneity. The overexpression of
      p53 that was found in 42% of the patients was of no prognostic significance.
      CONCLUSIONS: These data provide evidence that overexpression of cyclin D1 protein
      in resection material of squamous cell carcinomas of the head and neck is
      indicative of a poor prognosis, independently of other known prognostic factors.
      Whether overexpression of cyclin D1 may therefore be used to select patients for
      more intensive treatment should be examined in the context of a clinical trial.

PMID- 9158397
TI  - Absence of p53 mutations in squamous carcinomas of the tongue in nonsmoking and
      nondrinking patients younger than 40 years.
AB  - BACKGROUND: Although carcinoma of the tongue usually occurs in patients older
      than 60 years, up to 4% of these tumors may occur in patients younger than 40
      years. Many of the younger patients with this tumor have had no exposure or brief
      exposure to tobacco smoke or alcohol consumption, to which oral carcinoma is
      usually attributed. The molecular mechanism responsible for carcinogenesis in
      this group of patients is not known. OBJECTIVE: To assess the role of p53 gene
      mutation in oral carcinogenesis in a group of patients younger than 40 years with
      squamous carcinoma of the tongue. DESIGN: Squamous carcinoma cells were isolated
      from paraffin blocks by microdissection. DNA extracted from these cells was
      tested for the presence of p53 mutations by polymerase chain reaction and single
      stranded conformational polymorphism analysis. Mutations identified by this
      procedure were directly sequenced. Sections of the tumors were also stained using
      an immunoperoxidase immunohistochemical technique for expression of p53 protein.
      SUBJECTS: Eleven patients were selected on the basis of 2 criteria: presence of
      squamous cell carcinoma and age younger than 40 years. Six of the 11 patients had
      no history of measurable tobacco or alcohol exposure. RESULTS: Two mutations were
      detected among 11 tumors by single-stranded conformational polymorphism analysis,
      one in exon 4 and a second in exon 7. The former mutation consisted of G:C to C:G
      (guanine:cytosine to cytosine:guanine) transition in codon 72 (CGC to CCC), which
      would have resulted in the substitution of a proline residue for arginine. With
      the immunoperoxidase immunohistochemical technique for p53 protein, strong,
      diffuse nuclear staining was observed only in this tumor. The second mutation was
      a G:C to A:T (guanine:cytosine to adenine:thymine) transition in codon 248 (CGG
      to CGA), which would have resulted in no amino acid change since both mutant and
      wildtype codon sequences encode arginine. Weaker and more variable anti-p53
      immunostaining was noted in this and 4 other tumors. Five tumors were negative
      for p53 protein by the immunoperoxidase immunohistochemical technique.
      CONCLUSIONS: Our results suggest that p53 gene mutations are less frequent in
      squamous carcinomas occurring in nonsmoking young patients who do not drink
      alcohol than in young smokers or in the general population. Paucity of p53
      mutations may be explained by the absence of exposure to tobacco smoke or
      alcohol. These data leave unanswered the question of the molecular mechanism
      responsible for oral carcinogenesis in this group of patients and suggest that
      this group may be a suitable population in which to study genetic susceptibility
      to aerodigestive carcinoma isolated from the confounding factors of tobacco and
      alcohol exposure.

PMID- 9158398
TI  - Restoration of the G1 checkpoint and the apoptotic pathway mediated by wild-type
      p53 sensitizes squamous cell carcinoma of the head and neck to radiotherapy.
AB  - BACKGROUND: A significant number of squamous cell carcinomas of the head and neck
      (SCCHN) resist radiation treatment, the most common form of adjuvant therapy for
      this disease. The presence of a mutant form of the tumor suppressor gene p53 has
      been correlated with disruption of programmed cell death (apoptosis) and reduced
      cell cycle arrest, resulting in increased radiation resistance and survival.
      METHODS AND RESULTS: We introduced by means of an adenoviral vector a functional
      p53 gene into a radiation-resistant SCCHN cell line that harbors mutant p53.
      Replacement of wild-type p53 restored the G1 block and apoptosis in these cells
      in vitro. Moreover, introduction of wild-type p53 sensitized SCCHN-induced mouse
      xenografts to radiotherapy in vivo. CONCLUSION: The combination of p53
      replacement gene therapy with conventional radiotherapy may treat SCCHN more
      effectively.

PMID- 9158399
TI  - Human papillomavirus in head and neck squamous cell carcinomas in nonsmokers.
AB  - OBJECTIVE: To establish relationships between smoking status and human
      papillomavirus in head and neck squamous cell carcinomas. DESIGN: Human
      papillomavirus was detected in paraffin-embedded samples using E6-directed
      consensus primers and type-specific oligonucleotide probes. Patients were
      classified as smokers and nonsmokers. Alcohol use was also recorded. Data were
      analyzed by means of the Fisher exact test. Sequence analysis of exons 5 to 8 of
      the p53 gene was performed in tumor samples from nonsmokers. SETTING: Academic
      medical center in Paris, France. PATIENTS: One hundred eighty-seven consecutive
      patients with head and neck squamous cell carcinoma. RESULTS: The overall
      prevalence of human papillomaviral infection was 10.7%. Human papillomavirus
      occurred more frequently (P = .02) in oropharyngeal squamous cell carcinoma
      (18.6%) than in other locations (6.1%). There were 10 nonsmokers (5%). The 50%
      incidence of human papillomavirus in nonsmokers (95% confidence interval, 19%
      81%) differed significantly from the 8.5% incidence in smokers (95% confidence
      interval, 5%-14%; P = .003). No occupational risk factor was recorded in
      nonsmokers. None of these patients had p53 gene mutations in cancer cells.
      CONCLUSION: These findings suggest that human papillomavirus may play a role in
      head and neck squamous cell carcinomas in nonsmokers.

PMID- 9158400
TI  - Predictive factors for respiratory complications after tonsillectomy and
      adenoidectomy in children.
AB  - OBJECTIVE: To determine risk factors predictive of outcomes to aid in the cost
      effective preoperative evaluation and postoperative management of patients who
      are undergoing tonsillectomy and adenoidectomy for obstructed breathing during
      sleep. DESIGN: A historical cohort study with a nested case-control analysis that
      examined risk factors associated with postoperative respiratory complications.
      SETTING: Children's Medical Center of Dallas, Dallas, Tex, which is a pediatric
      referral hospital for secondary and tertiary pediatric care with both private and
      university-appointed physicians. PATIENTS: A convenience sample of 355 patients
      who were undergoing tonsillectomy and adenoidectomy for obstructed breathing
      during sleep throughout a 1-year period. INTERVENTION: None. MAIN OUTCOME
      MEASURE: The occurrence of postoperative complications, including airway
      obstruction, apneas with oxygen desaturations, airway interventions (e.g.,
      endotracheal intubation), or administration of supplemental oxygen, as they
      related to associated medical conditions (e.g., cerebral palsy or prematurity)
      and diagnostic tests (e.g., chest x-ray film and electrocardiogram). RESULTS:
      Five associated medical conditions (cerebral palsy; seizures; age, < or = 3
      years; congenital heart disease; and prematurity) were identified as important
      predictors of a complicated postoperative course using stepwise logistic
      regression analysis. Those children with an abnormal chest x-ray film or
      electrocardiogram were also identified as having an associated medical condition
      that was predictive of postoperative complications. CONCLUSIONS: Children with 1
      or more of the associated risk factors identified should be considered candidates
      for postoperative inpatient observation. A preoperative chest x-ray film and
      electrocardiogram were found to be of little predictive value, and they are
      probably not cost-effective screening tests for postoperative respiratory
      complications.

PMID- 9158401
TI  - Experimental trial of balloon-expandable, metallic Palmaz stent in the trachea.
AB  - OBJECTIVE: To determine the effect of the Palmaz stent, which has been
      successfully used to relieve airway obstruction in a small group of children, on
      the normal and operated on animal trachea. DESIGN: In this experimental trial,
      stents were placed bronchoscopically in the thoracic tracheae of 4 groups of 50
      anesthetized cats. The cats in group 1 (adults, n = 10) and group 2 (kittens, n =
      10) had normal tracheae; the cats in group 3 (adults, n = 15) underwent
      horizontal tracheal incision and closure; and the cats in group 4 (adults, n =
      15) underwent pericardial patch tracheoplasty. In group 3 and 4, the stents were
      inserted in 10 cats and 5 cats served as controls. Stents were inflated to a 15
      mm diameter in group 1 and an 8-mm diameter in the other groups. Half of the
      animals with stents were killed 5 weeks after the procedure, and the others, 10
      weeks after the procedure. SETTING: The Hospital for Sick Children, Toronto,
      Ontario. RESULTS: In group 1, 1 animal died of tracheal perforation. A mild cough
      was noted in 15 of the 39 cats with stents. In group 4, 3 cats had difficulty
      eating and lost weight. The results of esophagoscopy excluded esophageal
      inflammation or obstruction in these 3 animals. The results of bronchoscopy
      indicated a nonobstructing rim of granulation tissue at the end of the stent in
      15 of 20 cats in groups 1 and 2 and 17 of 20 cats in groups 3 and 4 and at the
      repair site in all animals with stents from groups 3 and 4. The results of
      autopsy indicated the cross-sectional area at the site of the stent was greater
      than normal in group 1 (P < .003) and smaller than the normal trachea at the site
      of the tracheoplasty in group 4 controls without stents (P < .02); however, the
      cross-sectional area at the tracheoplasty site with the stent was not smaller (P
      < .13). The results of histologic examination indicated a mild inflammatory
      reaction, with granulation tissue in all animals with stents, but in group 1,
      with overexpanded stents, the reaction was more severe, with epithelial
      ulceration, fibrosis, and sealed-off perforations in most animals. In group 3,
      the tracheae with stents had significantly more inflammatory reaction,
      granulation tissue, and epithelial damage than the controls without stents.
      CONCLUSIONS: The Palmaz stent provokes an inflammatory reaction in the normal
      trachea and the trachea recently operated on. With the exception of the group 1
      animals with overexpanded stents, this reaction is clinically insignificant. The
      Palmaz stent is able to maintain a normal lumen size after pericardial
      tracheoplasty in cats.

PMID- 9158402
TI  - Secondary healing of Mohs defects of the forehead, temple, and lower eyelid.
AB  - OBJECTIVE: To analyze the results of secondary healing of Mohs defects of the
      forehead, temple, and lower eyelid. DESIGN: Scars resulting from secondary
      healing in these 3 sites were rated by patient interviews and by analysis of
      postoperative photographs by 3 board-certified members of the American Academy of
      Facial Plastic and Reconstructive Surgery. SETTING: Private facial plastic and
      reconstructive surgery practice in Florida. PATIENTS: Patients with Mohs wounds
      of the forehead, temple, and lower eyelid that were allowed to heal by secondary
      intention between January 1, 1989, and December 31, 1993, who were available for
      follow-up. There were 10 wounds of the forehead, 6 of the temple, and 10 of the
      lower eyelid that were available for analysis. MAIN OUTCOME MEASURES: Wound
      color, contour, distortion of surrounding structures, presence of telangiectasias
      or paresthesias, pain or infection during healing, and overall cosmetic result.
      RESULTS: Color, contour, and overall scar cosmesis were rated using the following
      scale: poor (0), fair (1), good (2), and excellent (3). Telangiectasias,
      paresthesias, and pain or infection during healing were recorded as present or
      absent. The respective color and contour ratings for the 3 sites were 2.2 and 2.2
      for the forehead, 2.5 and 2.7 for the temple, and 2.7 and 3 for the lower eyelid
      according to patient interview and 1 and 1.3 for the forehead, 1 and 1.4 for the
      temple, and 2.6 and 2.5 for the lower eyelid according to surgeon analysis. Pain,
      infection, paresthesias, and distortion of surrounding structures were rare, but
      7 of 10 forehead and 4 of 6 temple wounds had telangiectasias. CONCLUSIONS: Many
      defects of the forehead and temple will heal with acceptable results. Partial
      thickness or small full-thickness lower eyelid wounds heal with excellent
      cosmetic and functional results. Patient satisfaction is greater than might be
      predicted by surgeon analysis of wound healing.

PMID- 9158403
TI  - Pigmented villonodular synovitis of the temporomandibular joint.
AB  - Pigmented villonodular synovitis is a proliferative disorder affecting the
      synovium and may be an aggressive local process with bone destruction and
      invasion of contiguous structures. Involvement of the temporomandibular joint is
      very rare. We report a rare case of pigmented villonodular synovitis of the
      temporomandibular joint that invaded the infratemporal fossa with bone
      destruction of the mandibular condyle. Magnetic resonance imaging was effective
      in delineating the extent of the lesion in the infratemporal fossa. Fine-needle
      aspiration cytology showed multinucleated giant cells and round or spindle-shaped
      cells with hemosiderin deposits. The tumor was resected en bloc through a
      combined temporocervical and infratemporal fossa approach. The postoperative
      histological diagnosis was a variant of pigmented villonodular synovitis. Fine
      needle aspiration cytology and magnetic resonance imaging proved to be useful in
      the preoperative diagnosis of pigmented villonodular synovitis of the
      temporomandibular joint and in the preoperative planning that is required to
      obtain adequate surgical margins.

PMID- 9158404
TI  - Synchronous lingual granular cell tumor and squamous carcinoma. A case report and
      review of the literature.
AB  - Granular cell tumor (GCT) is a benign lesion with a preference for subcutaneous
      sites. Marked pseudoepitheliomatous hyperplasia, seen in 10% of GCTs, might be
      misdiagnosed as squamous cell carcinoma (SCC), and GCT in the oral tissues has
      been referred to as a medical curiosity in the literature. We report the
      clinicopathologic, immunohistochemical, and ultrastructural findings in a case of
      coexistent SCC and GCT in the tongue. There is no evidence in this case that
      suggests malignant transition of the GCT to carcinoma. To the best of our
      knowledge, this is the first report of synchronous GCT and SCC in the oral
      cavity.

PMID- 9158405
TI  - Imaging quiz case 1. Glomus jugulare tumor of the temporal bone.

PMID- 9158406
TI  - Imaging quiz case 2. Glomus tympanicum tumor of the temporal bone.

PMID- 9158407
TI  - Imaging quiz case 3. Paraglottic laryngeal lipoma.

PMID- 9158408
TI  - Topical calcipotriol for treatment of inflammatory linear verrucous epidermal
      nevus.

PMID- 9158409
TI  - Should every day be melanoma monday?
AB  - To what extent am I my brothers' keeper? Perhaps this is one of the stickiest
      ethical questions that modern man, living in this increasingly impersonalized
      world, faces. For the medical profession, this quandary keeps resurfacing within
      the context of the present upheaval in the medical care delivery system and the
      redefinition and trend toward impersonalization of the physician-patient
      relationship. What responsibilities do I, as a physician, have to my patients?

PMID- 9158410
TI  - Cutaneous squamous cell carcinoma in human immunodeficiency virus-infected
      patients. A study of epidemiologic risk factors, human papillomavirus, and p53
      expression.
AB  - OBJECTIVE: To examine risk factors for the development of cutaneous squamous cell
      carcinoma (SCC) in a group of human immunodeficiency virus (HIV)-infected
      patients, including evaluation and detection of epidemiologic risk factors of
      human papillomavirus (HPV) and p53 expression. DESIGN: Case-control study during
      a 3-year period. SETTING: Dermatologic referral center. PATIENTS: Thirty-three
      HIV-infected patients who had 97 SCCs were compared with 24 HIV-infected patients
      who had 70 basal cell carcinomas (BCCs). MAIN OUTCOME MEASURES: Age, skin type,
      amount of sun exposure, actinic damage, family history of skin cancer and history
      of smoking and warts. Specimens of SCC and BCC were examined for HPV using
      polymerase chain reaction. Presence of p53 was examined using immunohistochemical
      analysis. Specimens from tumor-free, non-sun-exposed areas from these same
      patients were used as controls. RESULTS: Risk factors for the development of both
      types of carcinoma included fair skin type and excessive sun exposure (> 6 h/d
      during the previous 10 years). The HIV-infected patients with SCCs tended to have
      outdoor occupations. The location of SCCs favored the head and neck; BCCs were
      located on the trunk. Patients with SCCs had later-stage HIV disease than did
      patients with BCCs. Half of the patients with SCC had a history of genital or
      nongenital warts. Seventy-one percent (17/24) had a smoking history. No
      statistical difference existed between patients with SCCs and BCCs for history of
      smoking or warts. Human papillomavirus was not found in most of our SCC, BCC, or
      control specimens. However, 92% (22/24) of the SCC specimens and 90% (18/20) of
      the BCC specimens stained for p53. Control specimens from non-sun-exposed skin of
      HIV-infected patients did not stain for p53. Epidermal staining was present in
      95% (17/20) of tissue adjacent to SCCs and 47% (7/15) of tissue adjacent to BCCs.
      A significantly positive correlation existed between the amount of sun exposure
      and the amount of p53 staining seen in adjacent epidermal tissue (r = 0.07; P =
      .01). CONCLUSIONS: Risk factors for the development of SCCs and BCCs in HIV
      infected patients are similar: fair skin type and excessive sun exposure. Our
      study does not support that HPV is an oncogenic factor in the development of
      these cutaneous tumors but provides evidence that p53 overexpression may play a
      role.

PMID- 9158411
TI  - Analysis of tumor-infiltrating lymphocytes in cutaneous squamous cell carcinoma.
AB  - OBJECTIVE: To characterize tumor-infiltrating lymphocytes (TILs) within lesions
      of cutaneous squamous cell carcinoma (SCC) and related disorders. DESIGN: Case
      series with 1- and 2-color immunohistologic, molecular biological analysis of T
      cell clonality and in vitro cytotoxicity assays. SETTING: Academic medical
      center. PATIENTS: Twenty-one patients, including 6 with actinic keratoses, 4 with
      SCC in situ, and 11 with invasive SCC. RESULTS: CD8+ TILs were present within
      lesions of cutaneous SCC and AK. These cells constituted a variable minority of
      the total T-cell infiltrate, and many expressed a phenotype consistent with major
      histocompatibility complex-restricted cytotoxic T lymphocytes: CD3+, TIA1+, CD16
      , CD56-, CD57-. They also expressed HLA-DR, suggesting their activation in vivo.
      Virtually all T cells were T-cell receptor (TCR)-beta + delta, indicating that
      they expressed the TCR-alpha beta protein heterodimer. Molecular biological
      analysis of TCR-gamma gene rearrangements by the polymerase chain reaction and
      denaturing gradient gel electrophoresis technique indicated that the TILs were
      polyclonal. Functional studies suggested that TILs derived from SCC lesions were
      cytotoxic for autologous tumor cell targets. CONCLUSION: Tumor-infiltrating
      lymphocytes within cutaneous SCC lesions contain a subpopulation of polyclonal,
      major histocompatibility complex-restricted cytotoxic T lymphocytes expressing
      the TCR-alpha beta heterodimer.

PMID- 9158412
TI  - Differences in age and body site distribution of the histological subtypes of
      basal cell carcinoma. A possible indicator of differing causes.
AB  - OBJECTIVE: To assess if there are any significant differences in the sex,
      anatomical site, and age distribution of patients with different histological
      subtypes of basal cell carcinoma (BCC). DESIGN: Histopathology reports were
      analyzed with respect to the subtype of BCC, site of a tumor, and age and sex of
      a patient. SETTING: Histopathology reports were reviewed from 1 private
      laboratory that derived its cases from general practitioners, surgeons, and
      dermatologists. PATIENTS: Patients with BCC (N = 3885) for whom case data were
      received by the pathology laboratory from January 2, 1991, to June 12, 1991, were
      included in the study. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Superficial
      BCCs differed from other subtypes of BCC by occurring more commonly on the trunk
      and in younger patients. RESULTS: The mean age (56.8 years) of the patients with
      superficial BCCs was significantly lower than that of the patients with other
      subtypes of BCC who were examined (P < .001); the mean ages of the patients with
      these other subtypes were as follows: nodulosuperficial BCC, 62.9 years; nodular
      BCC, 63.9 years; nodulomorpheic BCC, 66.1 years; and morpheic BCC, 66.0 years.
      The majority of superficial BCCs occurred on the trunk and limbs (73.3%), while
      the majority of all other subtypes occurred on the head and neck. CONCLUSIONS:
      Superficial BCC differs from the other subtypes of BCC in terms of patient age
      and tumor site, and these findings may reflect differences in the etiology.

PMID- 9158413
TI  - bcl-2 vs p53 protein expression and apoptotic rate in human nonmelanoma skin
      cancers.
AB  - BACKGROUND: A failure in the apoptotic response after severe genomic damage could
      facilitate cell transformation and tumor development, and a constitutive
      overexpression of either p53 or bcl-2 protein in nonapoptotic tumor cells could
      signify a defective bax-mediated apoptosis. OBJECTIVES: To investigate whether a
      negative correlation occurs between these 2 proteins in nonmelanoma skin cancer
      and whether overexpression of either protein is associated with a low rate of
      spontaneous apoptosis. DESIGN: Immunohistochemical study of nonmelanoma skin
      cancer archive material. SETTING: University referral center. PATIENTS: White
      patients with tumors on sun-exposed skin areas (ie, 17 basal cell carcinomas and
      22 squamous cell carcinomas). MAIN OUTCOME MEASURES: Positivity for p53 and bcl-2
      were scored semiquantitatively on 4 levels, and the percentages of apoptotic
      cells were determined. RESULTS: A significant negative correlation between p53
      and bcl-2 expression was found in the basal cell carcinomas, but not in the
      squamous cell carcinomas, largely attributable to the low level of bcl-2 staining
      in the squamous cell carcinomas. Squamous cell carcinomas have a significantly
      higher number of apoptotic cells than basal cell carcinomas: 1.1% vs 0.6%,
      respectively. This spontaneous apoptosis decreases with increasing bcl-2 (in
      basal cell carcinoma), whereas it does not appear to be related to p53 level
      expression. CONCLUSIONS: These results indicate that a disturbance in either p53
      or bcl-2 suffices to enhance skin tumor formation by suppressing apoptosis; bcl-2
      appears to reduce the rate of spontaneous apoptosis, but an aberrant p53
      expression does not, and this factor may solely affect the apoptosis from
      exogenous genotoxicity.

PMID- 9158414
TI  - Systemic scleroderma. Multicenter trial of 1 year of treatment with recombinant
      interferon gamma.
AB  - OBJECTIVE: To confirm significant improvement of the skin score in systemic
      sclerosis by treatment with interferon gamma in a larger group of patients and to
      investigate on a molecular level the influence of interferon gamma on collagen
      type I messenger RNA expression. DESIGN: Open, noncontrolled multicenter study.
      SETTING: Five outpatient clinics specializing in the care of systemic
      scleroderma. PATIENTS: Thirty-two patients suffering from the diffuse or limited
      form of systemic sclerosis and progressive disease were recruited; 20 patients
      finished the study. INTERVENTION: Each patient received interferon gamma, 50
      micrograms subcutaneously 3 times a week for 1 year. MAIN OUTCOME MEASURE: Skin
      score, collagen type I messenger RNA in skin biopsy specimens. RESULTS: The
      patients who completed the study showed an unchanged median skin score after 1
      year of therapy. In addition, similar collagen type I messenger RNA levels were
      detected in skin biopsy specimens taken from involved skin before and after
      therapy in these patients. CONCLUSIONS: Treatment of systemic scleroderma with
      interferon gamma is associated with stabilization of the skin score and lack of
      worsening of visceral involvement.

PMID- 9158416
TI  - Pregnancy in patients with Hansen disease.
AB  - BACKGROUND: Three pregnancies occurred in a cohort of 40 patients with Hansen
      disease during a 6-year period. There are few recent reports in the English
      literature that deal with pregnancy in patients with Hansen disease. These 3
      cases are presented in the context of previously reported cohorts. OBSERVATIONS:
      In patient 1, symptoms of the disease appeared during pregnancy. In patient 2,
      reactivation vs reaction occurred during pregnancy in a previously treated
      patient. In patient 3, the fetus was exposed to 3 antimicrobial drugs during the
      first trimester. CONCLUSIONS: The pregnant state causes a relative decrease in
      cellular immunity. This decrease allows Mycobacterium leprae to proliferate,
      which may precipitate or worsen disease, leading to permanent nerve damage.
      Careful management of reactional states and treatment of patients with dapsone
      monotherapy can prevent this nerve damage. Infants are usually much less affected
      than mothers; however, selection of the mother's antimicrobial regimen must
      ensure adequate control of the bacteria while avoiding teratogenicity and in
      utero adverse effects.

PMID- 9158415
TI  - Loss of cutaneous delayed hypersensitivity reactions in nevus anemicus. Evidence
      for close concordance of cutaneous delayed hypersensitivity and endothelial E
      selectin expression.
AB  - BACKGROUND: The relationship of adhesion molecules in the dermis to
      immunologically mediated cutaneous inflammation can be understood by focusing on
      a serendipitous phenomenon: a lack of dermatitis within the margins of a nevus
      anemicus (NA) in generalized contact dermatitis. The expression and induction of
      endothelial and epithelial adhesion molecules with intradermally injected
      cytokines were investigated. OBSERVATIONS: Nevus anemicus without dermatitis
      lacked histopathological changes consistent with inflammatory cellular
      infiltration. The surrounding skin of the dermatitic lesion expressed HLA-DR,
      intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1,
      and E-selectin on endothelial cells, and HLA-DR and ICAM-1 in the epidermis.
      However, the skin of the NA lacked endothelial E-selectin and epidermal HLA-DR
      and ICAM-1 expression. Interferon gamma, injected intradermally, induced
      endothelial and epidermal HLA-DR and ICAM-1 expression in the NA and surrounding
      normal skin. While interferon gamma strongly induced E-selectin expression on
      endothelial cells in normal skin, it failed to induce endothelial E-selectin
      expression in the NA. CONCLUSIONS: This study suggests that vessels in the NA do
      not respond normally to proinflammatory cytokines, at least at the level of E
      selectin expression. The absence of keratinocyte ICAM-1 and HLA-DR expression in
      the NA lesion in contact dermatitis is likely caused by the absence of
      infiltrating lymphocytes, rather than by the intrinsic unresponsiveness of
      keratinocytes to interferon gamma. Among the endothelial cell adhesion molecules
      in delayed hypersensitivity, E-selectin appears to be indispensable in recruiting
      circulating T lymphocytes to the skin.

PMID- 9158417
TI  - The impact of the human immunodeficiency virus on the human papillomavirus
      epidemic.
AB  - OBJECTIVE: To examine how human immunodeficiency virus (HIV) infections affect
      human papillomavirus (HPV) infections. DATA SOURCE: MEDLINE was searched for
      relevant publications. STUDY SELECTION: All studies dealing with both HIV and HPV
      infections were reviewed. DATA EXTRACTION: Publications with clinically relevant
      data were included in the present analysis. DATA SYNTHESIS: A critical analysis
      of the data described in these articles was performed without formal statistical
      calculations. CONCLUSIONS: Results revealed that immunocompromised individuals
      have an increase prevalence of HPV-associated lesions and neoplasia.
      Immunosuppressed patients (eg, those who have undergone transplantation or those
      who have been treated with chemotherapy and/or radiation therapy) have a higher
      rate of HPV infections. Human papillomavirus and HIV appear to be important
      cofactors for developing cervical and anal dysplasia and carcinoma. Individuals
      who are seropositive for HIV have an increased prevalence of HPV infections, a
      more rapid progression of the disease, and a higher number of invasive
      carcinomas. The presence of HPV DNA, extent of disease, and potential for
      malignant transformation also appear to correlate with the degree of
      immunosuppression. Individuals with a CD4 cell count under 0.20 x 10(9)/L (<
      200/microliters) are at greatest risk. Treatment options for immunocompromised
      individuals remain similar to those for normal hosts; however, immunocompromised
      individuals have a much higher rate of recurrence. Improved immunostimulant
      and/or antiviral therapy is needed for HIV-seropositive individuals with
      widespread genital involvement. Control of both the HPV and the HIV epidemics
      involves at least 3 levels of intervention: better antiviral drugs, frequent
      monitoring for disease progression in infected persons, and better education to
      reduce spread of the disease.

PMID- 9158418
TI  - Recombinant cytokine treatment for scleroderma. Can the antifibrotic potential of
      interferon-gamma be realized clinically?

PMID- 9158419
TI  - Is favorable prognosis of squamous cell carcinoma of the skin due to efficient
      immune surveillance?

PMID- 9158420
TI  - Nonpitting induration of the back. Scleredema adultorum of Buschke type III.

PMID- 9158421
TI  - Hypopigmented, hyperkeratotic macules in a teenager. Lichen sclerosus et
      atrophicus.

PMID- 9158422
TI  - Zosteriform papular eruption. Zosteriform lichen planus.

PMID- 9158423
TI  - Acute papulosquamous eruption of the extremities demonstrating an isomorphic
      response. Inverse pityriasis rosea (PR).

PMID- 9158424
TI  - Screening in neurofibromatosis type 1.

PMID- 9158425
TI  - Middle-term evolution of patients with advanced cutaneous T-cell lymphoma treated
      with high-dose recombinant interleukin-2.

PMID- 9158426
TI  - Melanoma incidence: if it quacks like a duck...

PMID- 9158427
TI  - Improvement of psoriasis vulgaris with oral nickel dibromide.

PMID- 9158428
TI  - Chromoblastomycosis produced by Aureobasidium pullulans in an immunosuppressed
      patient.

PMID- 9158429
TI  - Pseudoxanthoma elasticum with generalized cutaneous laxity.

PMID- 9158430
TI  - Basal cell carcinoma occurring in multiple familial trichoepithelioma: detection
      of loss of heterozygosity in chromosome 9q.

PMID- 9158431
TI  - Intraepidermal neutrophilic IgA dermatosis in a patient with advanced human
      immunodeficiency virus infection.

PMID- 9158432
TI  - Reduction of UV-A radiation induced by calcipotriol in the treatment of vulgar
      psoriasis with oral psoralen plus UV-A.

PMID- 9158433
TI  - Make love not war. Violence and weapon carrying in music videos.

PMID- 9158434
TI  - Violence and weapon carrying in music videos. A content analysis.
AB  - BACKGROUND: The positive portrayal of violence and weapon carrying in televised
      music videos is thought to have a considerable influence on the normative
      expectations of adolescents about these behaviors. OBJECTIVES: To perform a
      content analysis of the depictions of violence and weapon carrying in music
      videos, including 5 genres of music (rock, rap, adult contemporary, rhythm and
      blues, and country), from 4 television networks and to analyze the degree of
      sexuality or eroticism portrayed in each video and its association with violence
      and weapon carrying, as an indicator of the desirability of violent behaviors.
      METHODS: Five hundred eighteen videos were recorded during randomly selected days
      and times of the day from the Music Television, Video Hits One, Black
      Entertainment Television, and Country Music Television networks. Four female and
      4 male observers aged 17 to 24 years were trained to use a standardized content
      analysis instrument. Interobserver reliability testing resulted in a mean (+/-
      SD) percentage agreement of 89.25% +/- 7.10% and a mean (+/- SD) kappa of 0.73 +/
      0.20. All videos were observed by rotating 2-person, male-female teams that were
      required to reach agreement on each behavior that was scored. Music genre and
      network differences in behaviors were analyzed with chi 2 tests. RESULTS: A
      higher percentage (22.4%) of Music Television videos portrayed overt violence
      than Video Hits One (11.8%), Country Music Television (11.8%), and Black
      Entertainment Television (11.5%) videos (P = .02). Rap (20.4%) had the highest
      portrayal of violence, followed by rock (19.8%), country (10.8%), adult
      contemporary (9.7%), and rhythm and blues (5.9%) (P = .006). Weapon carrying was
      higher on Music Television (25.0%) than on Black Entertainment Television
      (11.5%), Video Hits One (8.4%), and Country Music Television (6.9%) (P < .001).
      Weapon carrying was also higher in rock (19.8%) and rap (19.5%) videos than in
      adult contemporary (16.1%), rhythm and blues (6.9%), and country (6.3%) videos (P
      = .002). The videos with the highest level of sexuality or eroticism were found
      to be less likely to contain violence (P < or = .04). CONCLUSION: Because most
      music videos are between 3 and 4 minutes long, these data indicate that even
      modest levels of viewing may result in substantial exposure to violence and
      weapon carrying, which is glamorized by music artists, actors, and actresses.

PMID- 9158435
TI  - Self-administration of over-the-counter medication for pain among adolescents.
AB  - OBJECTIVE: To examine over-the-counter (OTC) medication use and self
      administration of medication among adolescents. DESIGN: In-person survey.
      SETTINGS: Three public junior high schools in Halifax, Nova Scotia. PARTICIPANTS:
      Six hundred fifty-one junior high school students (7th, 8th, and 9th grades).
      MAIN OUTCOME MEASURES: A questionnaire regarding OTC medication use and self
      administration for head: stomach; ear and throat; muscle, joint, and back; and
      menstrual pains. RESULTS: Of those who reported taking medication, many
      adolescents (58.7%-95.9%) reported taking OTC medications for each pain.
      Medications and knowledge about medications were obtained from a variety of
      sources, primarily parents. Self-administration was widespread; 58.3% to 75.9% of
      adolescents reported taking an OTC medication for pain without first checking
      with an adult in the previous 3 months. Self-administration of medication without
      the knowledge of adults increased significantly from grades 7 to 9 for all types
      of pain. Girls tended to self-administer medication more than boys. Higher levels
      of pain frequency and intensity were related to higher levels of self
      administration for all pains except muscle, joint, and back pain. Adolescents
      reported that they began to self-administer medication between the ages of 11 and
      12 years. CONCLUSIONS: Although a relatively responsible picture of self
      administration of medication emerges, some adolescents engaged in inappropriate
      OTC medication use (eg, the common use of aspirin), highlighting the importance
      of providing adolescents with correct information about these medications.

PMID- 9158436
TI  - Comparison of injury during cadet basic training by gender.
AB  - OBJECTIVES: To describe the rate and distribution of injuries during basic
      training in male and female cadets and to assess the contribution of pretraining
      conditioning and height to the male-female differential in injuries. DESIGN:
      Cohort study. SETTING: The US Military Academy, West Point, NY. PARTICIPANTS: A
      total of 558 cadets from the class of 1995 at the US Military Academy. MAIN
      OUTCOME MEASURES: The rate of injuries resulting in 1 or more days excused from
      physical activities per 100 cadets and the rate of injuries resulting in
      hospitalization of 1 night or longer per 100 cadets. RESULTS: Women had 2.5 times
      the rate of injuries as men and 3.9 times the rate of injuries resulting in
      hospitalization. Women had significantly more stress fractures and stress
      reactions than men. The median number of days excused from physical activities
      for women's injuries was significantly higher than that from men's injuries.
      Pretraining conditioning, measured by performance on a 2-mile (3.2-km) run,
      accounted for approximately half the difference in rates of injuries between men
      and women; differences in height among men and women did not account for
      differences in injury rates. CONCLUSIONS: The women had a higher risk for injury
      during military training than men. Increased pretraining conditioning may
      substantially decrease the risk for injury.

PMID- 9158437
TI  - Weight-independent cardiovascular fitness and coronary risk factors.
AB  - BACKGROUND: It is unclear whether cardiovascular fitness influences risk factors
      for coronary artery disease and non-insulin-dependent diabetes mellitus
      independently of level of body fat because fitness is often measured in tasks
      that involve moving body weight (eg, running) and because body weight and level
      of body fat are correlated. OBJECTIVE: To measure fitness during a task in which
      body weight was controlled experimentally (ie, supine cycling). DESIGN: Cross
      sectional. PARTICIPANTS: Seventy-four children, 7 to 13 years of age, recruited
      through school flyers and newspaper advertisements, varying in level of body fat
      from 7% to 61%. There were 31 boys and 43 girls; 35 were white and 39 were black.
      MAIN INDEPENDENT VARIABLES: Cardiovascular fitness was expressed as submaximal
      heart rate while cycling at a power output of 49 W, and level of body fat was
      measured with dual x-ray absorptiometry. MAIN OUTCOME MEASURES: Blood pressure
      and levels of triglycerides, total cholesterol, high-density lipoprotein
      cholesterol, low-density lipoprotein cholesterol, insulin, glucose, and
      glycohemoglobin. RESULTS: Controlling for age and sex, level of body fat was
      significantly (P < .01) related to unfavorable levels of systolic blood pressure
      (r = 0.32), triglycerides (r = 0.42), high-density lipoprotein cholesterol (r = 
      0.31), insulin (r = 0.50), and total cholesterol to high-density lipoprotein
      cholesterol ratio (r = 0.37); submaximal heart rate was not significantly
      correlated with any of the other variables. CONCLUSIONS: When cardiovascular
      fitness was measured in a weight-independent task, it was not significantly
      related to level of body fat or the major coronary artery disease and non-insulin
      dependent diabetes mellitus risk factors. In addition, we confirmed previous
      findings that higher levels of body fat are associated with a very unfavorable
      risk profile.

PMID- 9158439
TI  - Sleep problems of elementary school children. A community survey.
AB  - OBJECTIVE: To examine the prevalence, co-occurrence, and correlates of sleep
      problems among elementary school children. DESIGN: Survey. SETTING: General
      community. PARTICIPANTS: The parents of 987 children aged 5 to 12 years completed
      an anonymous survey distributed in their children's schools. MAIN OUTCOME
      MEASURES: The survey form asked about background characteristics, children's
      sleep environment, sleep habits, adult interventions, sleep history, and specific
      sleep problems. RESULTS: Bedtime resistance was the most prevalent sleep problem
      (27%). Sleep-onset delays (11.3%), night waking (6.5%), morning wake-up problems
      (17%), and fatigue complaints (17%) were also common. Among children with sleep
      onset problems, 80% displayed bedtime resistance, while 34% of bedtime resisters
      had onset problems. Onset problems correlated with more fears, night waking,
      psychiatric and medical conditions, the need for reassurance and caregiver
      proximity, and history of sleep problems. Bedtime resistance was associated with
      an inconsistent bedtime and falling asleep away from bed. Those who display
      delayed sleep onset and bedtime resistance also wake later, suggesting that sleep
      phase delays may maintain these problems. CONCLUSIONS: The results confirm
      bedtime resistance as parents principal sleep-related complaint for this age
      group but reveal a subgroup more prone to insomnia, night waking, and anxiety
      related features. Phase delay findings suggest the importance of limits around
      wake-up time as well as bedtime. The results highlight the importance of
      distinctly evaluating bedtime resistance, sleep onset, sleep maintenance, waking,
      and emotional adjustment.

PMID- 9158438
TI  - Factors associated with early maternal postpartum discharge from the hospital.
AB  - OBJECTIVE: To examine if mothers discharged from the hospital after 1 night's
      stay or less (early discharge) differ from those discharged from the hospital
      after 2 or 3 nights' stay (regular discharge) in demographic, economic,
      behavioral, health status, and health services risk factors associated with
      maternal and infant well-being. DESIGN: Bivariate and logistic comparisons of
      women discharged from the hospital early or after a regular hospitalization as
      reported in the 1988 National Maternal and Infant Health Survey. PARTICIPANTS:
      Postpartum women. MAIN OUTCOME MEASURE: Postpartum discharge from the hospital
      after 1 night's stay or less in the hospital. RESULTS: Early discharge from the
      hospital occurred for 12.3% of 3,865 366 women. Logistic regression revealed 8
      factors that were associated with early discharge from the hospital: less than a
      high school education, aged older than 35 years, inadequate prenatal care, lack
      of private insurance or receipt of Medicaid for delivery, giving birth in the
      western United States, plans to breast-feed, and care by midwives. Two factors
      were associated with an increased likelihood of a regular discharge from the
      hospital: report of a hospitalization during pregnancy and giving birth in the
      Midwest or Northeast. CONCLUSIONS: Significant numbers of mothers discharged from
      the hospital early manifested health and social risk factors associated with poor
      health outcomes. Economic factors seemed an important motivation for early
      discharge from the hospital, as did inadequate use of health services. Since
      brief hospitalization is prevalent, clinicians and administrators must assure
      that the objectives of medical contact during childbirth are met, if not through
      hospitalization, then through other mechanisms.

PMID- 9158440
TI  - Increased prevalence of abnormal Papanicolaou smears in urban adolescents.
AB  - OBJECTIVE: To determine the secular trend in the prevalence of cervical dysplasia
      as evidenced by abnormal Papanicolaou smear results in sexually active
      adolescents. DESIGN: Descriptive case series. SETTING: Outpatient department of
      an urban public hospital. PARTICIPANTS: All sexually active adolescents with
      Papanicolaou smear results recorded during 2 periods: January 1, 1982, through
      December 31, 1983 (n = 577), and January 1, 1992, through December 31, 1993 (n =
      871). MEASUREMENTS: Age, ethnicity, patient care location in which the
      Papanicolaou smear preparation was performed, and Papanicolaou smear results were
      obtained for each patient. For patients with more than 1 Papanicolaou smear
      result during the specified period, only the first result was included in this
      study. Papanicolaou smear results were classified according to the Bethesda
      system as within normal limits, benign cellular change, atypical squamous cells
      of undetermined significance, lowgrade squamous intraepithelial lesion, or high
      grade squamous intraepithelial lesion. Any Papanicolaou smear classified as
      atypical squamous cells of undetermined significance or low- or high-grade
      squamous intraepithelial lesion was defined as abnormal. RESULTS: The prevalence
      of abnormal Papanicolaou smear results was 2.8% in 1982 through 1983 vs 11.7% in
      1992 through 1993; prevalence odds ratio was 4.7 (95% confidence interval, 2.7
      8.3). The higher rate of abnormal Papanicolaou smear results in 1992 through 1993
      persisted after controlling for age, patient care location, and ethnicity in a
      logistic regression model (adjusted prevalence odds ratio, 5.0; 95% confidence
      interval, 2.8-8.9). The prevalence of benign cellular change was 8.7% in 1982
      through 1983 vs 20.1% in 1992 through 1993; prevalence odds ratio was 2.7 (95%
      confidence interval, 1.9-3.8). CONCLUSIONS: The prevalence of abnormal
      Papanicolaou smear results has significantly increased in the last decade in
      sexually active adolescents seen at a city hospital clinic. The results of this
      study emphasize the importance of routine Papanicolaou smear screening for all
      sexually active female adolescents.

PMID- 9158441
TI  - Bicycle-riding circumstances and injuries in school-aged children. A case-control
      study.
AB  - OBJECTIVE: To identify bicycle-riding circumstances associated with bicycle
      related injury among school-aged children. DESIGN: Case-control. SETTING: One
      metropolitan emergency department and 3 suburban emergency departments. SUBJECTS:
      Consecutive sample of children aged 7 through 18 years who experienced bicycle
      related trauma and control children seen for non-bicycle-related trauma (matched
      for age within 1 year, sex, and area of residence [urban vs suburban]). METHODS:
      Parents and case children were interviewed by telephone about the bicycle ride
      resulting in their visit to the emergency department. Parents and control
      children were interviewed about their most recent bicycle ride. The survey
      instrument addressed the following potential risk factors: helmet use, bicycle
      speed, road conditions, riding location, bicycle condition, an adult presence,
      riding destination, bicycle style, and stunt riding. RESULTS: Interviews were
      completed with 47 (73%) of 64 eligible case children and 42 (69%) of 61 control
      children with the following age distribution: 27 (30%) of the interviews were
      completed with children aged 7 to 9 years, 40 (45%) of the interviews were
      completed with children aged 10 to 14 years, and 22 (25%) of the interviews were
      completed with children aged 15 to 18 years. Fourteen children (16%) were wearing
      helmets. There was a high degree of agreement between parent and child responses,
      higher for case children than for control children. In univariate analyses,
      injury was associated with riding with other children (vs riding alone or with
      adults), riding fast or slow (vs normal speed), riding a BMX-style (motocross)
      bicycle (vs another standard or multispeed style bicycle), playing on the bicycle
      (vs going to school or other purposeful or nonpurposeful trip), and riding only
      on the sidewalk (vs in the street). More case children than control children were
      farther than 3/4 mile (> 1.2 km) from home (38% vs 19%, P = .05). Multiple
      logistic regression identified' slow riding speed (odds ratio, 10.3;95%
      confidence interval, 1.6-66.8), distance from home farther than 3/4 mile (> 1.2
      km) (odds ratio, 3.7;95% confidence interval, 1.1-12.5), and riding on the
      sidewalk (odds ratio, 6.1;95% confidence interval, 1.8-20.5) as independent risk
      factors for injury. CONCLUSIONS: This study identifies 3 counterintuitive but
      apparently strong behavioral risk factors for bicycle injuries treated in an
      emergency department in children aged 7 through 18 years in the Chicago (III)
      area. These findings will need to be confirmed in larger samples from a wider
      range of locales. In addition to stressing the importance of wearing a helmet
      when riding a bicycle, it may be desirable to include the findings of this study
      in anticipatory guidance discussions with school-aged children.

PMID- 9158442
TI  - The influence of medroxyprogesterone on the duration of breast-feeding in mothers
      in an urban community.
AB  - OBJECTIVE: To assess the effect of medroxyprogesterone acetate on lactation when
      it is given immediately post partum. DESIGN: Prospective cohort study with follow
      up through 16 weeks post partum. SETTING: Urban teaching hospital in Baltimore,
      Md. PARTICIPANTS: Consecutive sample (N = 95) of mothers who were delivered of
      healthy, term newborns, had home telephones, received either medroxyprogesterone
      or nonhormonal contraception at discharge, and were currently breast-feeding
      their newborns. MAIN OUTCOME MEASURES: Lactation (duration and frequency) and
      timing of first introduction of formula were measured by weekly telephone
      interviews. RESULTS: Maternal characteristics included the mean +/- SD maternal
      age (24 +/- 5 years), race (90% African American), history of pregnancy (63%
      multiparous), marital status or relationship (50% married or living with
      partner), and medical assistance (81% of the recipients received aid). Women who
      were receiving medroxyprogesterone (n = 43) were older (P < .05) and were more
      likely to be married (P < .05) compared with those who were receiving nonhormonal
      contraception (n = 52). No other factors that were likely to influence lactation
      were significantly different. Groups did not differ in the baseline-planned
      duration of lactation. Follow-up data were obtained on 90 women (96%). The groups
      were comparable in the duration of lactation (medroxyprogesterone: 98%, 74%, 55%,
      47%, and 42% were breast-feeding at least once per day at 1, 4, 8, 12, and 16
      weeks, respectively [median, 10.14 weeks], vs nonhormonal contraception: 86%,
      70%, 47%, 36%, and 30%, respectively [median, 6.57 weeks] [P = .19]). The
      percentage of subjects who were exclusively breast-feeding at these times and the
      timing of formula introduction also did not differ by group. CONCLUSION:
      Medroxyprogesterone, when given to mothers in an urban community immediately
      after delivery, has no detrimental effect on the duration of lactation, frequency
      of lactation, and timing of introduction of formula within the first 16 weeks
      post partum.

PMID- 9158443
TI  - Clinician agreement on physical findings in child sexual abuse cases.
AB  - OBJECTIVE: To measure agreement among experienced clinicians regarding the
      interpretation of physical findings in child sexual abuse cases and to determine
      whether knowledge of clinical history affects the interpretation of the physical
      findings. DESIGN: Experienced clinicians rated colposcopic photographs on a scale
      of 1 to 5 with 1 being normal and 5 being clear evidence of penetrating injury.
      To answer an additional study question of whether clinical history affected
      interpretation, 4 clinicians rated 69 cases in which they were blinded to the
      patients' histories and 70 cases in which the patients' histories were available.
      The other 3 clinicians then rated the same cases with the presence or absence of
      history reversed. SETTING: All clinicians involved perform child sexual abuse
      examinations at tertiary care centers. PATIENTS: A total of 139 girls with Tanner
      stage 1 or 2 genitalia who were referred to a general pediatric clinic at an
      academic medical center for examination of possible sexual abuse. RESULTS: Half
      of the photographs were interpreted as indicating little or no evidence of abuse.
      Of those photographic sets that both readers could interpret, 39% were in perfect
      agreement and 77% disagreed by 1 category or less. Perfect agreement across all
      possible pairs of readers was 34.5%. Agreement was better when the patient's
      clinical history was unknown (29.3% vs 38.9%, P = .005). The kappa, a measure of
      interrater reliability, indicated poor agreement among clinicians. The combined
      kappa for the first group of clinicians was 0.22 without knowledge of clinical
      history and 0.11 with knowledge of clinical history. For the second group of
      clinicians, the kappa was 0.31 without knowledge of clinical history and 0.15
      with knowledge of clinical history. The overall kappa across all 7 clinicians
      disregarding clinical history was 0.20. Agreement was best for categories 1
      (normal, kappa = 0.28) and 5 (clear evidence of a penetrating injury, kappa =
      0.39). CONCLUSIONS: Clinicians educated and experienced in assessing child sexual
      abuse do not agree perfectly on the interpretation of photographs of genital
      findings in girls with Tanner stage 1 or 2 genitalia. Clinicians agree less when
      a patient's clinical history is available. Efforts should be directed at
      standardizing physical findings and avoiding overemphasis on physical findings in
      child sexual abuse cases.

PMID- 9158444
TI  - Children's exposure to violence in an urban setting.
AB  - OBJECTIVE: To assess the exposure to violence of a representative sample of
      children living in an inner-city public housing development. DESIGN: Self-report
      survey. SETTING: Chicago public housing development that covers 4 census tracts;
      population, 95% African American, 75% below the poverty level. PARTICIPANTS: One
      hundred forty-six African American youth, aged 7 through 13 years, completed the
      survey; 53% were male, mean and median ages, 11 years. Seventy-two children (case
      subjects) are involved in a community-based health and recreation program. They
      completed the survey prior to participating in a peer-mentoring violence
      prevention curriculum. The other 74 children (control subjects) were recruited by
      a community member going door to door. Control subjects were matched to case
      subjects for age, sex, and census tract. RESULTS: The case and control subjects
      were similar in their exposure to violence and so were grouped for analysis. Of
      the 146 children, 42% had seen someone shot and 37% had seen someone stabbed; 21%
      lived with someone who had been shot and 16% lived with someone who had been
      stabbed. Forty-seven percent of the girls and 55% of the boys had witnessed
      violence (P > .25). Almost all subjects (90%) felt safe at home. Two thirds (65%)
      of the children were not afraid to play outside, but almost half (43%) worried
      about getting hurt at school. CONCLUSIONS: These data, which describe a
      representative sample of children from an inner-city housing project, confirm the
      results from older clinic- and school-based convenience samples. In this low
      income community, children are frequently exposed to deadly violence. In contrast
      with other reports, girls here are not spared.

PMID- 9158445
TI  - Delivery of confidentiality assurances to adolescents by primary care physicians.
AB  - OBJECTIVE: To investigate physicians' practices in assuring confidentiality to
      adolescent patients. DESIGN: Mail survey. SETTING: California. PARTICIPANTS:
      Seven hundred eighty-six board-certified physicians in family practice, internal
      medicine, obstetrics and gynecology, or pediatrics (response rate, 65%). MAIN
      OUTCOME MEASURES: Physicians were asked the percentage of adolescent patients (15
      to 18 years old) with whom they discuss confidentiality during routine visits and
      the content of their assurances of confidentiality. A clinical vignette assessed
      physicians' knowledge of legal guidelines for confidential treatment of
      adolescents. RESULTS: Physicians reported discussing confidentiality with 53% (on
      average) of their adolescent patients. Eleven percent of physicians did not
      discuss confidentiality with any adolescent patients. Hierarchical linear
      regression used to control for other physician demographic and practice factors
      showed that female physicians were more likely to discuss confidentiality than
      were male physicians (R2 change = 0.03, P < .001). There was also an association
      between specialty and discussing confidentiality (R2 change = .04, P < .001);
      obstetricians and gynecologists were more likely to discuss confidentiality than
      were other primary care physicians (beta = .21, P < .001). Among physicians who
      discussed confidentiality, 64% assured unconditional confidentiality and 36%
      assured conditional confidentiality. When asked about legal guidelines for
      managing a 15-year-old patient with a sexually transmitted disease, 63% of
      physicians responded correctly, 5% responded incorrectly, and 31% were unsure of
      management guidelines. CONCLUSIONS: Physicians do not consistently discuss
      confidentiality with their adolescent patients. Most of the physicians who
      discuss confidentiality, with adolescents assure unconditional confidentiality,
      which is inconsistent with professional guidelines or the legal limitations of
      confidentiality.

PMID- 9158446
TI  - Pediatric residency training in the normal newborn nursery. A national survey.
AB  - OBJECTIVE: To determine how and what pediatric residency programs are teaching
      residents about normal newborn care in the nursery. DESIGN: A mailed survey
      distributed in 1994. PARTICIPANTS: All 237 known pediatric residency programs in
      the United States, Canada, and Puerto Rico. RESULTS: Survey response rate was 77%
      (184 of 237 questionnaires were returned and completed). In 40% of the programs,
      neonatologists were primarily responsible or co-responsible for teaching
      residents about management of normal newborns. A normal newborn nursery
      curriculum had been developed and implemented in 56% of the programs, 30% of
      programs were developing one, and 13% reported no curriculum. Specific
      instruction about breast-feeding was not offered in 16% of programs.
      Circumcisions were most commonly performed by obstetricians; anesthetic use was
      low (overall median use, 10%) but was more common (P < .002) when circumcisions
      were performed by pediatricians. The hospital environment and lack of faculty
      time were cited as the main barriers to teaching residents about normal newborn
      care. CONCLUSIONS: Although general pediatricians spend a substantial amount of
      practice time on newborn care, neonatologists were responsible for this teaching
      in almost half of the pediatric residency programs. Many programs have not
      developed a curriculum. Instruction about breast-feeding was not universal. Most
      pediatric residents do not learn to perform circumcisions. General pediatricians
      should be more involved in the development, implementation, and evaluation of
      comprehensive newborn nursery curricula to improve training in this important
      aspect of general pediatric practice.

PMID- 9158447
TI  - Radiological case of the month. Incarcerated umbilical hernia.

PMID- 9158448
TI  - Picture of the month. Filariasis.

PMID- 9158449
TI  - Pathological case of the month. Infantile acute hemorrhagic edema.

PMID- 9158450
TI  - Genital tuberculosis in an adolescent male.

PMID- 9158451
TI  - Chiropractic for children.

PMID- 9158452
TI  - The Student Pediatric Society: an intervention to promote a career in pediatrics.

PMID- 9158453
TI  - Family practitioner preparedness for pediatric emergencies.

PMID- 9158454
TI  - Attitudes of academic pediatricians with a specific interest in child abuse
      toward the spanking of children.

PMID- 9158455
TI  - Contour control, survival, and quality of life.

PMID- 9158456
TI  - The future of Britain's high security hospitals.

PMID- 9158457
TI  - New challenge for palliative care.

PMID- 9158458
TI  - Domestic violence and pregnancy.

PMID- 9158459
TI  - Patently confused.

PMID- 9158460
TI  - Japan to allow organ transplants.

PMID- 9158461
TI  - Hay fever drug to become prescription only.

PMID- 9158462
TI  - US endorses testing for cystic fibrosis in pregnant women.

PMID- 9158463
TI  - HIV transmitted by bone graft.

PMID- 9158464
TI  - Is hyperglycaemia an independent predictor of poor outcome after acute stroke?
      Results of a long-term follow up study.
AB  - OBJECTIVE: To determine whether raised plasma glucose concentration independently
      influences outcome after acute stroke or is a stress response reflecting
      increased stroke severity. DESIGN: Long-term follow up study of patients admitted
      to an acute stroke unit. SETTING: Western Infirmary, Glasgow. SUBJECTS: 811
      patients with acute stroke confirmed by computed tomography. Analysis was
      restricted to the 750 non-diabetic patients. MAIN OUTCOME MEASURES: Survival time
      and placement three months after stroke. RESULTS: 645 patients (86%) had
      ischaemic stroke and 105 patients (14%) haemorrhagic stroke. Cox's proportional
      hazards modelling with stratification according to Oxfordshire Community Stroke
      Project categories identified increased age (relative hazard 1.36 per decade; 95%
      confidence interval 1.21 to 1.53), haemorrhagic stroke (relative hazard 1.67;
      1.22 to 2.28), time to resolution of symptoms > 72 hours (relative hazard 2.15;
      1.15 to 4.05), and hyperglycaemia (relative hazard 1.87; 1.43 to 2.45) as
      predictors of mortality. The effect of glucose concentration on survival was
      greatest in the first month. CONCLUSIONS: Plasma glucose concentration above 8
      mmol/l after acute stroke predicts a poor prognosis after correcting for age,
      stroke severity, and stroke subtype. Raised plasma glucose concentration is
      therefore unlikely to be solely a stress response and should arguably be treated
      actively. A randomised trial is warranted.

PMID- 9158465
TI  - Randomised comparison between adrenaline injection alone and adrenaline injection
      plus heat probe treatment for actively bleeding ulcers.
AB  - OBJECTIVE: To compare endoscopic adrenaline injection alone and adrenaline
      injection plus heat probe for the treatment of actively bleeding peptic ulcers.
      DESIGN: Randomised prospective study of patients admitted with actively bleeding
      peptic ulcers. SETTING: One university hospital. SUBJECTS: 276 patients with
      actively bleeding ulcers detected by endoscopy within 24 hours of admission: 136
      patients were randomised to endoscopic adrenaline injection alone and 140 to
      adrenaline injection plus heat probe treatment. MAIN OUTCOME MEASURES: Initial
      endoscopic haemostasis; clinical rebleeding; requirement for operation;
      requirement for blood transfusion; hospital stay, ulcer healing at four weeks;
      and mortality in hospital. RESULTS: Initial haemostasis was achieved in 131/134
      patients (98%) who received adrenaline injection alone and 135/136 patients (99%)
      who received additional heat probe treatment (P = 0.33). Outcome as measured by
      clinical rebleeding (12 v 5), requirement for emergency operation (14 v 8), blood
      transfusion (2 v 3 units), hospital stay (4 v 4 days), ulcer healing at four
      weeks (79.1% v 74%), and in hospital mortality (7 v 8) were not significantly
      different in the two groups. In the subgroup of patients with spurting
      haemorrhage 8/27 (29.6%; 14.5% to 50.3%) patients from the adrenaline injection
      alone group and 2/31 (6.5%; 1.1% to 22.9%) patients from the dual treatment group
      required operative intervention. The relative risk of this was lower in the dual
      treatment group (0.17; 0.03 to 0.87). Hospital stay was significantly shorter in
      the dual treatment group than the adrenaline injection alone group (4 v 6 days, P
      = 0.01). CONCLUSION: The addition of heat probe treatment after endoscopic
      adrenaline injection confers an advantage in ulcers with spurting haemorrhage.

PMID- 9158467
TI  - Prospective study of Helicobacter pylori seropositivity and cardiovascular
      diseases in a general elderly population.

PMID- 9158466
TI  - Body weight: implications for the prevention of coronary heart disease, stroke,
      and diabetes mellitus in a cohort study of middle aged men.
AB  - OBJECTIVE: To determine the body mass index associated with the lowest morbidity
      and mortality. DESIGN: Prospective study of a male cohort. SETTING: One general
      practice in each of 24 British towns. SUBJECTS: 7735 men aged 40-59 years at
      screening. MAIN OUTCOME MEASURES: All cause death rate, heart attacks, and stroke
      (fatal and non-fatal) and development of diabetes, or any of these outcomes
      (combined end point) over an average follow up of 14.8 years. RESULTS: There were
      1271 deaths from all causes, 974 heart attacks, 290 strokes, and 245 new cases of
      diabetes mellitus. All cause mortality was increased only in men with a body mass
      index (kg/m2) < 20 and in men with an index > or = 30. However, risk of
      cardiovascular death, heart attack, and diabetes increased progressively from an
      index of < 20 even after age, smoking, social class, alcohol consumption, and
      physical activity were adjusted for. For the combined end point the lowest risks
      were seen for an index of 20.0-23.9. In never smokers and former smokers, deaths
      from any cause rose progressively from an index of 20.0-21.9 and for the combined
      end point, from 20.0-23.9. Age adjusted levels of a wide range of cardiovascular
      risk factors rose or fell progressively from an index < 20. CONCLUSION: A healthy
      body mass index in these middle aged British men seems to be about 22.

PMID- 9158468
TI  - Helicobacter pylori infection and coagulation in healthy people.

PMID- 9158469
TI  - Comparison of physiotherapy, manipulation, and corticosteroid injection for
      treating shoulder complaints in general practice: randomised, single blind study.
AB  - OBJECTIVE: To compare the efficacy of physiotherapy, manipulation, and
      corticosteroid injection for treating patients with shoulder complaints in
      general practice. DESIGN: Randomised, single blind study. SETTING: Seven general
      practices in the Netherlands. SUBJECTS: 198 patients with shoulder complaints, of
      whom 172 were divided, on the basis of physical examination, into two diagnostic
      groups: a shoulder girdle group (n = 58) and a synovial group (n = 114).
      INTERVENTIONS: Patients in the shoulder girdle group were randomised to
      manipulation or physiotherapy, and patients in the synovial group were randomised
      to corticosteroid injection, manipulation, or physiotherapy. MAIN OUTCOME
      MEASURES: Duration of shoulder complaints analysed by survival analysis. RESULTS:
      In the shoulder girdle group duration of complaints was significantly shorter
      after manipulation compared with physiotherapy (P < 0.001). Also the number of
      patients reporting treatment failure was less with manipulation. In the synovial
      group duration of complaints was shortest after corticosteroid injection compared
      with manipulation and physiotherapy (P < 0.001). Drop out due to treatment
      failure was low in the injection group (17%) and high in the manipulation group
      (59%) and physiotherapy group (51%). CONCLUSIONS: For treating shoulder girdle
      disorders, manipulation seems to be the preferred treatment. For the synovial
      disorders, corticosteroid injection seems the best treatment.

PMID- 9158470
TI  - The social origins of infantile colic: questionnaire study covering 76,747
      infants.
AB  - OBJECTIVE: To describe risk factors for infantile colic. DESIGN: Questionnaire
      administered by health visitors. SETTING: Sheffield. SUBJECTS: Mothers of 76,747
      infants born between 1 August 1975 and 31 May 1988, interviewed when the infant
      was 1 month old. MAIN OUTCOME MEASURES: Reporting of infantile colic and its
      duration; weight of infant leeding, state of the home, socioeconomic
      characteristics of the parents, parents' age, and mother's parity. RESULTS: The
      odds of reporting infantile colic were increased with breast feeding (odds ratio
      of breast v bottle feeding 1.35 (95% confidence interval 1.28 to 1.43)),
      increasing parental age, lower parity, increasing parental age at leaving full
      time education, and more affluent homes and districts of residence. In a logistic
      regression analysis, mother's age and parity and socioeconomic factors remained
      the most important risk factors for the reporting of infantile colic (each P <
      0.005), and the effect of breast feeding was attenuated (odds ratio of breast v
      bottle feeding 1.09 (1.02 to 1.15)). CONCLUSION: At a population level, dietary
      factors contribute little to mothers' reporting of infantile colic, and dietary
      change should not be the primary intervention.

PMID- 9158471
TI  - Polymyalgia rheumatica and temporal arteritis: diagnosis and management.

PMID- 9158472
TI  - ABC of clinical haematology. Haematological emergencies.

PMID- 9158473
TI  - What will a primary care led NHS mean for GP workload? The problem of the lack of
      an evidence base.
AB  - Ongoing negotiations on the general practitioner contract raise the question of
      remunerating general practitioners for increased workload resulting from the
      shift from secondary to primary care. A review of the literature shows that there
      is little evidence on whether a shift of services from secondary to primary care
      is responsible for general practitioners' increased workload, and scope for
      making generalisations is limited. The implication is that general practitioners
      have little more than anecdotal evidence to support their claims of greatly
      increased workloads, and there is insufficient evidence to make informed
      decisions about remunerating general practitioners for the extra work resulting
      from the changes. Lack of evidence does not, however, mean that there is no
      problem with workload. It will be increasingly important to identify mechanisms
      for ensuring that resources follow workload.

PMID- 9158474
TI  - Socioeconomic determinants of health: community marginalisation and the diffusion
      of disease and disorder in the United States.
AB  - This article describes the cascading diffusion of "inner city problems" of
      disease and disorder in the United States--from the huge marginalised inner city
      communities of the largest municipalities, first along national travel routes to
      smaller cities, and then from central cities into surrounding more affluent
      suburbs-following the pattern of the daily journey to work. Public policies and
      economic practices which increase marginalisation act to damage the "weak ties"
      of the community social networks which bind central city neighbourhoods into
      functioning units. Spreading disease and disorder can be interpreted as indices
      of the resulting social disintegration, which is driven by policy. This "failure
      of containment" in the United States should serve as a warning for cities in
      Europe against reducing the municipal and other services that they provide to
      "unpopular" subpopulations.

PMID- 9158475
TI  - Introducing the postoperative care team. Effective postoperative care remains
      surgeons' role.

PMID- 9158476
TI  - Introducing the postoperative care team. Such teams deserve a trial of
      effectiveness and cost.

PMID- 9158477
TI  - Introducing the postoperative care team. Royal College of Surgeons has training
      programme for surgical trainees.

PMID- 9158478
TI  - Introducing the postoperative care team. Better to define and enhance role of
      ward surgical nurses.

PMID- 9158479
TI  - Why people stay healthy.

PMID- 9158480
TI  - Exploitative collaborative research must be discouraged.

PMID- 9158481
TI  - Persistent fever in pulmonary tuberculosis. Older doctors had more experience of
      tuberculosis.

PMID- 9158482
TI  - Persistent fever in pulmonary tuberculosis. Several factors were not considered.

PMID- 9158483
TI  - Public scare has not deterred Finnish teenagers from using oral contraceptives.

PMID- 9158484
TI  - Sight tests to detect glaucoma. Reliability of screening procedures and
      effectiveness of treatment need to be assessed.

PMID- 9158485
TI  - Sight tests to detect glaucoma. Entitlement to free sight tests should be
      reviewed.

PMID- 9158486
TI  - Systemic lupus erythematosus complicated by antiphospholipid antibody syndrome.
      Young women should be referred to an obstetrician or gynaecologist.

PMID- 9158487
TI  - Systemic lupus erythematosus complicated by antiphospholipid antibody syndrome.
      Pulse treatment with cyclophosphamide would have been more appropriate.

PMID- 9158488
TI  - The tobacco industry and scientific publications. Challenges on grounds of self
      evident potential bias are not unfair.

PMID- 9158489
TI  - The tobacco industry and scientific publications. Findings of scientists who were
      and were not funded by tobacco industry were strikingly different.

PMID- 9158490
TI  - More intensive care unit beds are needed.

PMID- 9158491
TI  - Submucosal haemorrhage--or ruptured nodule in a multinodular goitre? Ultrasound
      scan suggested recent haemorrhage in a left upper pole thyroid nodule.

PMID- 9158492
TI  - Journals and the Internet. Medical journals will continue to be important in
      prioritising important data.

PMID- 9158493
TI  - Journals and the Internet. Use of the Internet for on line peer review must be
      explored further.

PMID- 9158494
TI  - Journals and the Internet. Copyright must be reconsidered.

PMID- 9158495
TI  - Regulations on registration of a fetus papyraceus need to be revised.

PMID- 9158496
TI  - Risk of lung cancer needs to be studied in younger patients who keep pet birds.

PMID- 9158497
TI  - CS gas is not a chemical means of restraining a person.

PMID- 9158498
TI  - Talk works--if the patient is willing.

PMID- 9158499
TI  - Irrigating fluids in endoscopic surgery.

PMID- 9158500
TI  - Tubulogenesis by microvascular endothelial cells is mediated by vascular
      endothelial growth factor (VEGF) in renal cell carcinoma.
AB  - OBJECTIVE: To investigate the role of vascular endothelial growth factor (VEGF)
      in tumour angiogenesis in renal cell carcinoma (RCC). MATERIALS AND METHODS: The
      expression of VEGF was examined in tissue samples from 25 patients with RCC using
      the reverse-transcriptase polymerase chain reaction (RT-PCR). Cellular
      localization of VEGF was studied in normal kidney and RCC tissues. Tube formation
      by human omental microvascular endothelial (HOME) cells co-cultured with A498 RCC
      cells was quantified in a three-dimensional collagen gel using computer-image
      analysis. RESULTS: RT-PCR detected VEGF m-RNA in tissue from 20 of 25 patients
      with RCC. An immunohistochemical study revealed that VEGF was primarily localized
      in the cytosol of normal renal tubule cells and RCC cells. Tube formation by HOME
      cells was increased in the presence of A498 cells overexpressing VEGF mRNA,
      induced by exogenous VEGF in a dose-dependent manner and completely inhibited by
      an anti-VEGF antibody. CONCLUSION: VEGF, which is produced and released from RCC
      cells, may elicit tumour angiogenesis by inducing microvessel tubulogenesis in
      patients with RCC. The co-culture system may be useful for screening inhibitors
      of tumour angiogenesis in RCC.

PMID- 9158501
TI  - Significant association between simple renal cysts and arterial blood pressure.
AB  - OBJECTIVE: To test the hypothesis that there is an association between simple
      renal cysts and arterial blood pressure (BP). PATIENTS AND METHODS: The study
      comprised a review of the case-notes of 115 patients (mean age 67.7 years, range
      31-91) in whom renal cyst(s) was an incidental ultrasonographic finding, and 115
      age- and sex-matched control patients. The notes were reviewed without knowledge
      of the origin or treatment. RESULTS: The systolic and diastolic BP were
      significantly higher in patients with a cyst(s) than in control patients (P =
      0.031 and P = 0.0034; mean difference 6.9 mmHg and 5.0 mmHg, respectively). In
      those aged 30-70 years, the presence of one or more simple renal cysts increased
      the risk of having a diastolic BP > or = 95 mmHg from seven in 58 to 17 in 58
      patients (P = 0.038). CONCLUSION: The association between simple renal cysts and
      higher arterial BP probably arises from underlying renal disease causing both.
      Occasionally it is possible that renal ischaemia caused by cyst expansion, and
      therefore increased renin release, generates the elevation in BP. If so, methods
      to identify such cysts should be developed.

PMID- 9158502
TI  - Do simple renal cysts cause hypertension?

PMID- 9158503
TI  - Pressure-flow studies in the diagnosis of bladder outlet obstruction: a study
      comparing suprapubic and transurethral techniques.
AB  - OBJECTIVE: To compare suprapubic and transurethral methods of measuring
      intravesical pressure in a group of men undergoing investigation for lower
      urinary tract symptoms (LUTS), to identify which urodynamic variables are
      affected by the presence of an urethral catheter during the voiding phase, and
      consequently whether there is any change in the grading of bladder outflow
      obstruction (BOO) using the commonly recognised grading systems. PATIENTS AND
      METHODS: Thirty-five men with LUTS underwent both suprapubic and transurethral
      pressure-flow studies during a single session. Standard pressure flow variables
      were measured in all patients with both methods, enabling calculation of
      obstruction using the commonly used grading systems, i.e. the Abrams-Griffith
      number, linear passive urethral resistance ratio (LPURR) and urethral resistance
      algorithm (URA). RESULTS: There were statistically significant differences
      between the methods in the mean values of maximum flow rate and the detrusor
      pressure at that maximum: 60% of men were in the same LPURR class with either
      method. Using the transurethral method, 26% of patients increased the LPURR class
      by one and 6% by two classes. Using the Abrams-Griffiths nomogram, 17% moved from
      a classification of equivocal to obstructed and 3% from unobstructed to
      equivocal. Using the criterion of a value of URA > 29, 57% were obstructed using
      the suprapubic and 74% using the transurethral method. CONCLUSION: According to
      the method used, there were differences in the classification of obstruction
      between the suprapubic and transurethral routes; transurethral studies tended to
      indicate greater obstruction. The interpretation of urodynamic studies should
      take into account the technique used and where the route is transurethral, the
      smallest catheter available should be used.

PMID- 9158504
TI  - The ice-water test in the diagnosis and treatment of the neurogenic bladder.
AB  - OBJECTIVE: To determine the usefulness of the ice-water test (IWT) in the
      diagnosis and treatment of neurological bladder disease. PATIENTS AND METHODS:
      The IWT was carried out in 148 patients with neuropathic bladder dysfunction
      resulting from a traumatic lesion, to assist in their diagnosis and treatment,
      and in 130 patients with neuropathic bladder dysfunction and multiple pathogenic
      disorders; the results of the IWT were used to classify those patients with
      hyperactive bladders. RESULTS: The IWT was positive in 95% of patients affected
      by complete and in 86% of patients with incomplete medullary lesions. The IWT in
      patients with lower motor neuron medullary lesions was always negative. The test
      was used diagnostically in all patients with lower and in 43% of those with upper
      motor neuron lesions. In the latter, it was used in 48% of patients as a
      rehabilitation method during the medullary-shock phase to accelerate the
      appearance of the micturition reflex. In 9% of patients it was used to induce
      micturition during cystography. CONCLUSION: Because it is simple to perform, the
      IWT is a useful complement to urodynamic examinations in patients with
      neurological bladder disease and in patients with micturitional disorders that
      are otherwise difficult to interpret.

PMID- 9158505
TI  - The urodynamic evaluation of neuromodulation in patients with voiding
      dysfunction.
AB  - OBJECTIVES: To determine which patients with voiding dysfunction might be
      suitable for treatment with neuromodulation, using urodynamics to obtain an
      objective measure of improvement and to illustrate the effect of neuromodulation
      on voiding dysfunction. PATIENTS AND METHODS: Patients were selected for
      implantation of a neuroprosthesis using a urodynamic evaluation before and during
      subchronic stimulation; 27 such patients (four men and 23 women, mean age 33
      years, SD 15) were evaluated. RESULTS: Of the 27 patients, the 17 who responded
      well to neuromodulation all had hypocontractile detrusors and sphincter
      hypertonicity; sphincter relaxation during micturition was impaired. The
      urodynamic evaluation showed that these patients were not obstructed. Of 10
      patients with spastic pelvic floor syndrome, nine responded well to the
      treatment. Those not responding to neuromodulation had mainly acontractile
      detrusors. CONCLUSION: The ideal candidates for neuromodulation are those
      patients with a spastic pelvic floor syndrome or with a hypocontractile detrusor,
      in combination with sphincter instability, and impaired sphincter relaxation. An
      increase of bladder contractility, enhancement of sphincter relaxation and
      decrease in bladder capacity and residual urine are the most important features
      of the response.

PMID- 9158506
TI  - The female tetraplegic: an admission of urological failure.
AB  - OBJECTIVE: To present the long-term follow-up of female patients with tetraplegia
      managed in our unit, many of who require permanent indwelling catheters or
      urinary diversions that lead to significant complications and associated
      morbidity. PATIENTS AND METHODS: Eighty-four female tetraplegics (mean age 31
      years, range 13-81) were followed for a mean of 9 years (range 2-30). Three
      groups of patients were identified, depending on their neurology; 27 patients had
      complete lesions (Frankel A), 20 had incomplete lesions with poor functional
      recovery (Frankel B/C) and 37 had incomplete lesions with good function (Frankel
      D/E). RESULTS: The patients with complete lesions (Frankel A) were difficult to
      manage, with 23 of the 27 (85%) treated using indwelling catheters. Three
      patients underwent diversion and for one patient, the carer performs clean
      intermittent catheterization (CIC). Of the 20 patients with Frankel B/C lesions,
      14 have permanent indwelling catheters, three are able to perform CIC and three
      void by controlled triggering of detrusor contractions (reflex voiding). The 37
      patients with Frankel D/E lesions fared better and only three (8%) require
      permanent catheters. Of the others, four (11%) use CIC (one following a
      cystoplasty) and most (30, 81%) use reflex voiding. Most of the 40 patients with
      permanent catheters had significant problems with bladder stones (55%), leakage
      and by-passing (35%), and recurrent symptomatic infections (33%). Patients
      performing CIC fared better, with most needing anticholinergic therapy or
      subtrigonal phenol; patients who used reflex voiding also needed these two
      treatments at some stage. Four patients (two with ileal loops and two with
      indwelling catheters) developed dilated upper tracts. CONCLUSIONS: The urological
      status of female patients following cervical cord injury depends on the level of
      injury and recovery. Most patients with Frankel A-C lesions have permanent
      indwelling catheters and most patients with Frankel D or E lesions void with
      controlled triggering or use CIC. Although upper tract dilation was seen in only
      5%, patients had significant morbidity related to the bladder.

PMID- 9158507
TI  - The fate of the 'modern' artificial urinary sphincter with a follow-up of more
      than 10 years.
AB  - OBJECTIVE: To assess the long-term outcome of patients who had an artificial
      urinary sphincter (AUS) implanted between 10 and 15 years ago. PATIENTS AND
      METHODS: Of 68 patients who had an AUS implanted more than 10 years ago, 61 were
      followed with sufficient detail for analysis. Thirty-four had a neuropathic
      bladder with sphincter dysfunction, 15 had post-prostatectomy sphincter weakness
      incontinence and 12 further patients had a variety of indications. RESULTS: The
      61 patients experienced a total of 58 major complications and 49 have required at
      least one revision procedure. Currently eight (13%) patients are satisfactorily
      continent with their original AUS in situ and 29 others have a satisfactory
      revised AUS. Thus 37 of 61 (61%) are continent using an AUS at least 10 years
      after first implantation. Eleven patients died and of these two had a
      satisfactory original AUS in situ and seven had successful revisions. In two
      patients the AUS failed but they were considered unfit for revision. Four female
      patients were continent and used intermittent catheterization after the
      explantation of eroded AUS cuffs. In seven patients the AUS was abandoned; two of
      these patients reverted to condom drainage and five had continent or incontinent
      urinary diversions fashioned. Thus, if those who died with a functioning AUS are
      included, 46 of 61 (75%) achieved long-term continence with the AUS. CONCLUSIONS:
      Despite the high complication and revision rate, these results show that
      acceptable continence rates can be achieved in the long-term, particularly in the
      male neuropathic bladder and in those with post-prostatectomy sphincter weakness.
      Many of the complications encountered may be less common with the current re
      designed models of the AUS. However, it is essential that both surgeon and
      patient recognize and accept the likelihood of complications and revisions before
      using the AUS. The continued use of the AUS where simpler methods of obtaining
      continence are inappropriate remains justified.

PMID- 9158508
TI  - Intra-operative autotransfusion in radical cystectomy.
AB  - OBJECTIVE: To assess the feasibility of intra-operative autotransfusion (IAT) as
      a method of decreasing or avoiding homologous blood transfusion during radical
      cystectomy. PATIENTS AND METHODS: IAT was performed in 10 patients with bladder
      cancer who underwent radical cystectomy. The patients were divided into two
      groups: group 1 consisted of six patients without and group 2 of four patients
      with pre-deposited blood. Blood shed in the operative field was collected and
      processed with an IAT device. RESULTS: In group 1, the intra-operative blood loss
      ranged from 1.08 to 2.67 L (mean 1.82) and homologous blood transfusion ranged
      from 0 to 1 L (mean 0.47). The amount of autologous blood processed and
      transfused by the IAT device ranged from 0.38 to 0.98 L (mean 0.64). Two patients
      did not require homologous blood transfusion. In group 2, the volume of pre
      deposited blood ranged from 0.8 to 1.2 L (mean 0.9). The intra-operative blood
      loss ranged from 1.03 to 3.24 L (mean 1.8). The amount of processed autologous
      blood transfused ranged from 0.4 to 0.6 L (mean 0.45). None of the patients in
      group 2 required homologous blood transfusion. CONCLUSION: Although there are
      theoretical risks with IAT, they were not substantiated by the clinical data. IAT
      seems to be a feasible method of reducing or avoiding homologous blood
      transfusion in radical cystectomy. These results suggest that IAT in combination
      with pre-deposited blood will abolish the need for homologous blood transfusion
      during radical cystectomy.

PMID- 9158509
TI  - The clinical and histological features of transitional cell carcinoma of the
      bladder with microcysts: analysis of 12 cases.
AB  - OBJECTIVE: To describe the clinical course and histological features of
      transitional cell carcinoma (TCC) of the bladder with microcysts. PATIENTS AND
      METHODS: Among 940 patients with bladder TCC diagnosed at our institution during
      a 5 year period. 12 (1.2%; eight men and four women, mean age 71.1 years, range
      52-85) were diagnosed histologically as having microcystic TCC. Sections of the
      tumours were stained with haematoxylin and eosin, periodic acid-Schiff and Alcian
      blue and clinical data obtained from the patients' records. RESULTS: Of the 12
      patients with bladder TCC with microcysts, three had tumours confined to the
      epithelium, six had tumour invasion of the lamina propria and three had muscle
      invasion. One patient had low-grade TCC and 11 had high-grade TCC; six patients
      had a second primary tumour; three had a colon carcinoma, one a villous adenoma
      of the caecum, one a locally advanced carcinoma of the prostate and the last a
      squamous cell carcinoma of the uterine cervix. CONCLUSIONS: Microcystic TCC was
      associated with high-stage and high-grade bladder tumours and with other primary
      tumours, especially of the colon. Screening these patients for asymptomatic
      tumours of the colon is suggested.

PMID- 9158510
TI  - Multiple frequent recurrences in superficial transitional cell carcinoma of the
      bladder: is survival compromised by a conservative management strategy?
AB  - OBJECTIVE: To examine whether a strategy of bladder conservation is reasonable in
      patients with multiple frequent superficial recurrences of transitional cell
      carcinoma (TCC) of the bladder. PATIENTS AND METHODS: Fifty-four patients with
      pTa/pT1. G1/G2 tumours at diagnosis, with five or more recurrences at two or more
      cystoscopies within 2 years of diagnosis and a minimum follow-up of 4 years were
      identified. The patients were categorized according to outcome, i.e. disease
      settled, continuing high-activity disease and disease progression. RESULTS: Forty
      four patients did not progress, of whom 16 continued to have high-activity
      disease and 28 settled to a lower disease activity. One patient had a cystectomy
      for superficial disease. Nine patients progressed, six with muscle invasion in
      the bladder and three elsewhere in the urinary tract. Neither grade nor stage
      were predictive of recurrence. All but one of the patients with progression had
      both multicentric tumours at diagnosis and a positive cystoscopy at 3 months.
      Three patients died from their bladder cancer. CONCLUSION: A policy of endoscopic
      resections and intravesical chemotherapy or bacille-Calmette-Guerin, with
      cystectomy reserved until muscle-invasive disease develops, does not
      significantly compromise survival in patients with high-activity superficial TCC.
      Cystectomy for superficial disease is rarely necessary.

PMID- 9158511
TI  - Single-dose versus multiple instillations of epirubicin as prophylaxis for
      recurrence after transurethral resection of pTa and pT1 transitional-cell bladder
      tumours: a prospective, randomized controlled study.
AB  - OBJECTIVE: To compare single-dose and multiple instillations of epirubicin in the
      chemoprophylaxis of superficial bladder tumours. PATIENTS AND METHODS: In a
      prospective randomized and controlled study, 168 evaluable patients were assigned
      to three groups after transurethral resection of bladder tumour (TURBT) and
      histological confirmation of its superficial nature (pTa and pT1). The groups
      were comparable for tumour stage, grade and other tumour characteristics. In
      group 1, patients received a single dose of 50 mg epirubicin in 50 mL normal
      saline immediately after TURBT; group 2 received 50 mg epirubicin in 50 mL normal
      saline 1-2 weeks after TURBT and the instillations were repeated for 8 weeks and
      thereafter monthly to complete one year of treatment: group 3 (control group)
      received no adjuvant therapy after TURBT. The patients were assessed by cysto
      urethroscopy, urine cytology and DNA flow cytometry 8 weeks after resection and
      then every 3 months during the first 2 years and 6 monthly thereafter during the
      next 2 years. Intravenous urography was performed annually and when otherwise
      indicated. RESULTS: The recurrence rate was significantly lower in the patients
      treated with epirubicin than in the control group (24, 25 and 52%, respectively;
      P < 0.001). In those receiving epirubicin, the rates of recurrence were
      statistically comparable (P = 0.9). Patients who had a large tumour burden showed
      slightly lower recurrence rates with single-dose epirubicin than with delayed
      maintenance therapy but the difference was statistically insignificant. Patients
      with a history of bladder tumours before treatment had lower recurrence rates
      with maintenance treatment than with a single dose (34.6 and 22.6% in groups 1
      and 2, respectively); again this difference was statistically insignificant.
      Patients with grade 3 tumours showed a marginal difference in favour of
      maintenance therapy. The rates of progression amongst the three groups were 5.5,
      3.4 and 9.3%, respectively, with no significant differences. The overall toxicity
      rates were comparable in the two treated groups (22 and 25%). CONCLUSION: With
      the possible exception of grade 3 tumours, single-dose immediate epirubicin is as
      effective as delayed maintenance therapy, with the advantage of being more cost
      effective.

PMID- 9158512
TI  - A high-risk group for prostatism: a population-based epidemiological study in
      Korea.
AB  - OBJECTIVE: To evaluate the effect of sociodemographic, dietary and physical
      factors on prostatism in Korean men aged 50 and over. SUBJECTS AND METHODS: A
      community-based cross-sectional epidemiological study was performed in Yonchon
      County, Korea. The Korean version of the International Prostate Symptom Score
      (IPSS) was used to assess the severity of prostatism. Data on occupation, marital
      status, education, smoking habits, alcohol intake, daily consumption of
      nutrients, body mass index, abdominal circumference, waist-to-hip ratio, blood
      pressure, serum glucose, cholesterol, triglyceride and high-density lipoprotein
      (HDL) levels were analysed. The age-adjusted relative risk of these factors was
      calculated for moderate to severe prostatism (IPSS > or = 8). A multivariate
      analysis of all significant factors was performed to examine the joint effect of
      risk factors. RESULTS: Of 514 subjects, 119 (23.2%) had moderate to severe
      prostatism, the risk for which was related to age and alcohol consumption; waist
      to-hip ratio (which represents the degree of abdominal obesity) and the serum
      level of HDL showed a biphasic association with prostatism in the multivariate
      analysis. CONCLUSION: In addition to previously reported risk factors, these data
      suggest that there might be an association between the development of prostatism
      and abnormal lipid metabolism.

PMID- 9158513
TI  - Treatment-seeking behaviour and stated preferences for prostatectomy in Spanish
      men with lower urinary tract symptoms.
AB  - OBJECTIVES: To determine whether men in the community with lower urinary tract
      symptoms sought treatment, would choose to have a prostatectomy, and the factors
      that might influence their decision. SUBJECTS AND METHODS: The study was a cross
      sectional population survey using interviewers in the autonomous community of
      Madrid and comprised 2002 men aged > or = 50 years. The main outcome measures
      were self-reported International Prostate Symptom Scores (IPSS), treatment
      seeking behaviour and the patients' stated preference for prostatectomy. RESULTS:
      The response rate among eligible subjects was 68.1%; overall, 38.2% of men sought
      medical advice for their lower urinary tract symptoms. Whether a man sought
      medical advice was related to symptom severity, 'bothersomeness', interference in
      daily activities and his perception of the future; of these, bothersomeness and
      interference in activities were more likely to determine whether or not a man
      consulted his doctor. Most men in the sample (84.9%) reported that they would
      choose a prostatectomy, although this value depended on whether they had had a
      previous prostatectomy, were younger, and on the content of the information
      presented. Men were more likely to report that they would accept surgery if their
      doctor recommended it and less likely when presented with information on the
      outcomes of treatment. CONCLUSION: Many Spanish men with lower urinary tract
      symptoms do not seek medical advice for their symptoms, although most stated that
      they would accept a prostatectomy on the recommendation of their doctor. Further
      research should examine whether reported patient preferences correspond to actual
      behaviour and what is the most appropriate type of information to give to
      potential patients.

PMID- 9158514
TI  - British urological surgery practice: 1. Prostate cancer.
AB  - OBJECTIVE: To investigate the treatment of prostate cancer in the United Kingdom.
      METHODS: A postal survey was conducted of consultant urologists and general
      surgeons with an interest in urology to assess the current patterns of management
      of patients with prostate cancer in the UK and to determine patterns of clinical
      practice. RESULTS: Two-hundred and seventy-four replies were analysed. Radical
      radiotherapy (50%) and radical prostatectomy (29%) were the most favoured
      treatment options for patients < 70 years old with poorly differentiated T1
      disease; for those aged > 70 years, active treatment was favoured by 183 (67%)
      consultants with radical radiotherapy (37%) and hormonal intervention (29%) the
      most frequent choices. In well-differentiated T1 disease, active treatment was
      favoured by 226 (83%) of consultants for patients < 70 years, with radical
      prostatectomy (44%) the most frequent choice. For patients > 70 years,
      observational management was preferred by 190 (69%) of consultants. In poorly
      differentiated T1 prostate cancer, active treatment was favoured by 252 (91%) for
      patients < 70, with radiotherapy (50%) the most frequent choice and for patients
      > 70 years, active treatment was favoured by 67% with radical radiotherapy the
      most common preference being chosen, by 102 (37%). For asymptomatic locally
      advanced disease, 55% of consultants favoured active treatment, whilst 63%
      favoured the active treatment of asymptomatic metastatic disease. For patients
      with symptomatic metastatic disease, GnRH agonist therapy was the treatment of
      choice of 66% of urologists and was given as monotherapy by 44% or as part of
      maximal androgen blockade by 22%. In clinical practice, 82% of urologists have
      close links with oncology, available through joint clinics or on-site referral.
      However, < 5% of urologists refer patients to an oncologist before the
      development of hormone refractory disease. At relapse, only 53% of urologists
      referred their patients to oncologists or palliative-care clinicians. A wide
      variety of hormonal treatments was offered at relapse; only 24% of urologists
      treated their patients by antiandrogen withdrawal or introduction, which is
      currently the most effective second-line hormonal treatment for recurrent
      prostate cancer. CONCLUSION: There is a wide variation in the clinical management
      of prostate cancer and we recommend the establishment of standards of practice.

PMID- 9158515
TI  - Free and total prostate-specific antigen in a screened population.
AB  - OBJECTIVES: To determine whether the ratio of free to total (F/T) prostate
      specific antigen (PSA) can differentiate between men with prostate carcinoma or
      benign conditions in a screened population. SUBJECTS AND METHODS: Total and free
      serum PSA (measured using Delfia PSA assays, Abbott IMx and Hybritech Tandem E
      methods) were determined retrospectively in 1726 men aged 55-77 years, in whom 67
      prostate carcinomas were detected by screening with a digital rectal examination,
      transrectal ultrasonography, and total serum PSA level. Predictors for a positive
      biopsy result were estimated as a function of total PSA, free PSA and the
      combination of both. RESULTS: There was an excellent correlation between the
      Delfia ProStatus, the Abbott IMx and the Hybritech Tandem E assays. Compared with
      the total serum PSA level, the F/T ratio improved the specificity significantly
      only in those men with a total PSA of > or = 7 ng/mL. Using the information given
      by the total and free PSA values, a maximum sensitivity of 75% at a specificity
      of 74% was obtained for the whole PSA range from 4 to 10 ng/mL; the maximum
      sensitivity was 79% with a specificity of 71%. CONCLUSION: The optimal
      mathematical combination of free and total serum PSA improves the specificity of
      total serum PSA level in detecting prostate carcinoma more than the does the F/T
      PSA ratio.

PMID- 9158516
TI  - Analysis of glycosaminoglycans in human prostate by high-performance liquid
      chromatography.
AB  - OBJECTIVE: To investigate changes in glycosaminoglycan (GAG) profiles in human
      prostatic tissue. MATERIALS AND METHODS: Seventeen human prostatic samples were
      examined; five were normal, six hyperplastic and six were cancerous. Prostatic
      proteoglycans were extracted with 4 mol/L guanidine-HCl containing protease
      inhibitors. After digestion of the freeze-dried proteoglycan extract with papain,
      the prostatic GAGs were purified. Total GAGs were measured by a modified
      dimethylmethylene blue (DMB) method. High-performance liquid chromatography
      (HPLC) was used to quantify the extracted GAGs. RESULTS: Six types of GAGs, i.e.
      chondroitin 4-sulphate (Ch-4S), chondroitin 6-sulphate (Ch-6S), dermatan sulphate
      (DS), chondroitin, heparan sulphate and hyaluronic acid, were analysed
      qualitatively and quantitatively. The total amount of GAGs was increased in
      hyperplastic and cancerous prostates, with the predominant components being DS
      and Ch-6S in these specimens. The Ch-S:DS ratio in cancerous prostate was
      significantly higher than that in normal and BPH tissue (P < 0.05). Moreover,
      chondroitin was increased in hyperplastic prostatic tissue (P < 0.01).
      CONCLUSIONS: These results suggest that an increase in chondroitin levels may be
      associated with hyperplastic change and an increase in the Ch-S:DS ratio may be
      related to the development of malignancy.

PMID- 9158517
TI  - When is bone scintigraphy necessary in the assessment of newly diagnosed,
      untreated prostate cancer?
AB  - OBJECTIVE: To evaluate the utility of bone scintigraphy in the assessment of
      newly diagnosed, untreated prostate cancer. PATIENTS AND METHODS: The probability
      of a positive bone scan for metastases was analysed for different threshold
      values of pre-treatment concentrations of prostate specific antigen (PSA),
      clinical stage, tumour grade based on biopsy, and age in 128 men (mean age 69
      years, range 50-90) with newly diagnosed, untreated prostate cancer. The overall
      survival probabilities estimated from PSA level, extent of bone metastases,
      tumour grade, clinical stage, and age were calculated using the product-limit
      method. RESULTS: The positive predictive values of PSA level for bone metastases
      at thresholds of 10 and 20 ng/mL were poor (27.5 and 47.5%, respectively) whereas
      similar threshold levels of PSA gave negative predictive values of 100 and 94%,
      respectively, for a positive bone scan. In a univariate analysis, the overall
      survival was significantly affected by the extent of bone scan pathology (P <
      0.001), the pre-treatment level of PSA (P < 0.001) and tumour grade (P = 0.01),
      whereas a multivariate analysis identified, in order of significance, tumour
      grade (P = 0.003), bone scan findings (P = 0.007) and PSA levels (P = 0.03) as
      independent prognostic factors. CONCLUSIONS: Bone scintigraphy seems to be
      unnecessary in the evaluation of newly diagnosed, untreated prostate cancer in
      patients with no clinical signs of bone pathology and serum PSA levels of < or =
      10 ng/mL. However, the bone scan accurately assesses bone metastases and the
      prognostic significance of bone scan findings is superior to that of serum PSA
      level.

PMID- 9158518
TI  - Morbidity of ultrasound-guided transrectal core biopsy of the prostate without
      prophylactic antibiotic therapy. A prospective study in 415 cases.
AB  - OBJECTIVE: To evaluate prospectively the incidence of complications following
      transrectal core biopsy of the prostate without prophylactic antibiotic therapy.
      PATIENTS AND METHODS: The study comprised 426 consecutive patients who underwent
      transrectal core biopsies of the prostate guided by transrectal ultrasonography
      (TRUS). The patients were requested to return a completed questionnaire 2 weeks
      after the examination; 415 patients (97.4%) did so. RESULTS: The predominant
      complications were haematuria (49.6%) and rectal bleeding (21.7%), which did not
      require treatment. Twelve patients (2.9%) developed fever and 11 of these were
      treated successfully with antibiotics. One recovered without treatment. One
      patient had urinary retention. CONCLUSION: In this study, most complications
      following TRUS-guided biopsies were minor and required no treatment. Automated
      needle biopsy is an acceptable option for biopsy of the prostate and does not
      provoke the need for prophylactic antibiotic therapy. However, it is mandatory to
      counsel patients before biopsy and to monitor the infection rate. The ultimate
      need for antibiotic prophylaxis remains to be determined.

PMID- 9158519
TI  - A comparative study of the distribution of ofloxacin and ciprofloxacin in
      prostatic tissues after simultaneous oral ingestion.
AB  - OBJECTIVES: To determine the levels of two quinolones, ofloxacin and
      ciprofloxacin, potent broad-spectrum antibiotics with very good oral
      bioavailability and low minimum inhibitory concentrations (MICs) for most
      pathogens, in the prostates of patients who underwent transurethral resection of
      the prostate (TURP) after oral ingestion for surgical prophylaxis. PATIENTS AND
      METHODS: Twenty-eight patients with BPH requiring a TURP ingested 250 mg of both
      drugs 2-4 h before operation. The levels of the drugs in the serum and prostate
      were measured using high-performance liquid chromatography and the levels of both
      drugs determined at the 6 and 9 o'clock positions in the prostate to examine any
      local variations in drug concentration. RESULTS: Ofloxacin concentrations were
      significantly higher in the serum and prostatic tissues compared with
      ciprofloxacin for the same dose, but its penetrance into the prostate was lower.
      This mainly reflected its higher oral bioavailability. Both drugs were present in
      concentrations 50% higher at the 6 o'clock than at the 9 o'clock position but
      both exceeded the MICs for most Gram-negative organisms except Pseudomonas.
      CONCLUSION: Ofloxacin has the advantage against ciprofloxacin of exceeding the
      MICs for Staphylococcus and Chlamydia. However, ciprofloxacin has the advantage
      of having prostate-to-serum ratios of unity, but for the same dose the prostatic
      concentrations of ofloxacin is significantly higher.

PMID- 9158520
TI  - Gender reversal in 46XX congenital virilizing adrenal hyperplasia.
AB  - OBJECTIVE: To review the results of gender reversal in six patients with 46XX
      congenital virilizing adrenal hyperplasia (CVAH). PATIENTS AND METHODS: Fifty-one
      patients with 46XX CVAH were seen in an 8 year period; 45 were managed by
      conventional feminizing genitoplasty, but six underwent gender reversal and were
      managed as males. The clinical decision for gender reversal was made after
      appropriate counselling and was based primarily on parental choice, this being
      influenced significantly by a delayed diagnosis in four patients. Surgical
      management consisted of gonadectomy, excision of Mullerian structures and staged
      hypospadias repair/ chordee correction in four patients, and circumcision in two
      completely masculinized children. RESULTS: All six boys are well adjusted to
      their gender of rearing, with ages ranging from 3 years to 16.5 years (mean 8.5)
      at the time of review. Two children have normal penises and four have a
      satisfactory result after two-stage repair of hypospadias/chordee. CONCLUSION:
      Most patients with 46XX CVAH are preferably raised as females and require a
      feminizing genitoplasty. However, the clinical decision may be influenced by many
      factors, including delay in diagnosis, social bias and the premium on male
      rearing in certain communities. When male rearing is chosen, early gonadectomy
      and excision of Mullerian structures, together with staged hypospadias repair,
      gives satisfactory results.

PMID- 9158521
TI  - Correlation of the endoscopic and radiological anatomy of congenital obstruction
      of the posterior urethra and the external sphincter.
AB  - OBJECTIVE: To determine whether the external sphincter is distal to congenital
      occlusion of the posterior urethra in boys by correlating endoscopic video
      recorded information with cysto-urethrographic observations and assessing the
      anatomy of the disease. PATIENTS AND METHODS: This study reviewed the endoscopic
      and radiographic findings in 42 boys (mean age 42 months, range newborn to 14
      years), using material from a videotape library, and correlated these with the
      pre-operative cystogram. The nature of the obstructive lesion and its
      relationship to the verumontanum and the external sphincter was assessed.
      RESULTS: Of the 42 boys, 36 had the proximal extent of the external sphincter
      identified on the endoscopic video recording to be above the posterior urethral
      membrane; 22 of the membranes were obstructive. The proximal extent of the
      external sphincter was identified on the static cystogram images of only 31 of
      the 38 boys examined, but only ever above the posterior urethral membrane.
      CONCLUSION: The proximal extent of the external sphincter, i.e. that portion
      which is most prominent endoscopically, is proximal to the membrane in congenital
      obstruction of the posterior urethra.

PMID- 9158522
TI  - Acute epididymitis in boys: are antibiotics indicated?
AB  - OBJECTIVES: To report the results of using supportive therapy only, rather than
      antibiotics, in managing boys with acute sterile epididymitis. PATIENTS AND
      METHODS: From 1991 to 1995, 48 boys presented with acute epididymitis. The
      diagnosis was confirmed by radionuclide scan in 43 cases, ultrasonography in one,
      surgical exploration in one and physical examination in three. Urine was
      collected for microscopy and culture: if pyuria was detected, antibiotics were
      prescribed. If the urine analysis was normal, the patient was advised to minimize
      physical activity and analgesics were prescribed. RESULTS: Of the 48 boys, five
      (10%) had pyuria; seven patients with either no urine tested or negative urine
      culture were given antibiotics. The remaining 36 were managed with supportive
      therapy only. The mean follow-up was 87 days (with three patients lost to follow
      up). No boys showed any evidence of testicular atrophy or other complications.
      CONCLUSION: Only a minority of boys with acute epididymitis, as defined by
      increased flow on radionuclide scanning of the scrotum, have a bacterial
      aetiology. For those without pyuria or positive urine culture, the condition is
      self-limiting and does not lead to testicular atrophy. We recommend that for boys
      with acute epididymitis who have no urinary abnormalities, antibiotics are not
      indicated. The aetiology of acute sterile epididymitis in boys remains obscure.

PMID- 9158523
TI  - Penile constriction by foreign bodies: the use of a dental drill.

PMID- 9158524
TI  - Limited sub-coronal incision for insertion of semi-rigid penile prostheses.

PMID- 9158525
TI  - Vaginal stone in a teenager.

PMID- 9158526
TI  - Urinary retention in a child secondary to Hirschsprung's disease.

PMID- 9158527
TI  - Penile metastases from carcinoma of the prostate.

PMID- 9158528
TI  - Reduction of flutamide-induced alanine aminotransferase elevation after
      replacement by bicalutamide in a patient with N+ disease treated with maximal
      androgen blockade as a primary treatment.

PMID- 9158529
TI  - Balanitis xerotica obliterans in monozygotic twins.

PMID- 9158530
TI  - Bladder rupture caused by an intravenous urogram.

PMID- 9158531
TI  - An unexpected complication of urinary stomata.

PMID- 9158533
TI  - Frank haematuria during pregnancy due to placenta praevia percreta.

PMID- 9158532
TI  - Congenital fistula of the penile urethra.

PMID- 9158534
TI  - Cystitis associated with allopurinol.

PMID- 9158535
TI  - Management of superficial bladder cancer.

PMID- 9158536
TI  - Prostatic laser ablation versus transurethral resection of the prostate.

PMID- 9158537
TI  - Using a cytoscope sheath to perform urethrovesical anastomosis.

PMID- 9158538
TI  - Radical prostatectomy from three UK centres.

PMID- 9158540
TI  - The effect of frequent quizzes on short- and long-term academic performance.
AB  - This investigation examined the effect of frequent quiz administration on the
      performance of dental students on course examinations, post-tests, and attitudes
      toward instruction. Students in an introductory radiology course were randomly
      divided into two groups. Quiz Group (QG) students were given a quiz at the
      beginning of each class, while students in the Control Group (CG) did not take
      the quizzes. All students took a midterm and final examination as well as post
      tests at four months and ten months after the end of the course. Students also
      completed a questionnaire assessing the course and instructor. The QG scored
      higher than the CG on all exams, but these differences were significant only for
      the midterm and final exams (p < 0.05) and not the post-tests (p > 0.05).
      Evaluations of course content and instructor performance were significantly
      higher among QG students regarding appropriateness of examinations and overall
      evaluation of course (p < 0.05). Frequent quizzes enhance short-term performance
      on examinations and lead to more favorable student evaluations, but the effects
      on long-term retention of knowledge are not significant.

PMID- 9158539
TI  - Report prepared for the Health Technology Assessment panel of the NHS Executive
      on the diagnosis, management, treatment and costs of prostate cancer in England
      and Wales.

PMID- 9158541
TI  - Analyzing the sources of unreliability in fixed prosthodontics mock board
      examinations.
AB  - Mock board examinations in fixed prosthodontics were submitted to
      generalizability analysis in order to determine which sources of unwanted
      variance of measurement contribute to grade decisions and whether this lack of
      reliability is of practical significance. Students completed approximately three
      fixed prosthodontics test cases during their final year of clinic, and each case
      was scored by two faculty members. Of the subsamples of students where two test
      cases (trials) per student were graded by the same two raters, the subsamples
      with the highest and the lowest inter-rater reliability coefficients were chosen.
      Typical generalizability coefficients (reliability considering both raters and
      trials as sources of error) are much lower than the inter-rater reliability
      estimate, and the standard error of measurement is 80 percent of a grade interval
      on a five-point scale. In all analyses, the largest source of variance was the
      student-by-trial interaction, accounting for about 80 percent of the standard
      error of measurement or one-half a grade on a five-point scale. Even in the
      subsample with lowest inter-rater reliability, rater, rater-by-student
      interaction, and rater-by-trial interaction made no contribution to measurement
      error. Nor did students show evidence of improving over time. There is no
      possible improvement through the use of rater calibration or additional raters
      that would equal the improvement made by using two test cases rather than one.
      The concept of gradient of generalizability is introduced, and implications for
      initial licensure examinations are discussed.

PMID- 9158542
TI  - A comparison of self-reported dental health attitudes and behavior between
      selected Japanese and Australian students.
AB  - To compare cross-cultural differences of dental health behavior, 376 dental
      students in Japan and 213 in Australia were surveyed using a twenty-item
      Hiroshima University-Dental Behavior Inventory (HU-DBI) questionnaire (in
      Japanese and English versions respectively). The mean DBI score of Year 1
      Australian students was significantly greater than that of their Japanese peers
      (Australian 6.56, Japanese 5.57; P < 0.001), which suggested a higher level of
      dental health awareness in Australian students on entry. Only 7 percent of the
      Japanese students had been told by their dentist that they were performing a high
      level of plaque control, as contrasted with 50 percent of the Australian
      students. Furthermore, while only a small proportion of the Australian students
      (8 percent) reported a belief that they may eventually require dentures, 37
      percent of the Japanese students held this belief (P < 0.001). The mean HU-DBI
      score of the Japanese students was lower than that of the Australian students
      until Year 4. Differences between the genders were not a major feature.

PMID- 9158543
TI  - An outcomes assessment of a hybrid-PBL course in treatment planning.
AB  - As part of an ongoing process of curriculum development, a new course was
      developed at the University of British Columbia (UBC) to address problems such as
      lack of student enjoyment of the learning process, poor student preparedness for
      clinical treatment planning, and underdeveloped critical thinking skills in
      students beginning their clinical experience. The new course utilized a hybrid
      problem-based learning (PBL) format that provided students with an overview in
      lecture format while encouraging active learning in small group tutorials and
      seminars. Half the second-year class was randomly selected to participate in the
      new course, while the other half received the standard lectures on the subject.
      An outcomes assessment examined whether the aforementioned problems had been
      addressed in the new course. Course participants completed a post-course
      evaluation, and all students completed a self-assessment of their preparedness
      and progress in treatment planning and diagnostic. Clinical instructors, who were
      blind to the identity of the new course participants, were asked to independently
      assess each student using the same criteria. Results indicate that students who
      participated in the hybrid-PBL course enjoyed the learning process and later
      rated themselves as being better prepared and improving more in the areas of
      treatment planning and diagnostic records than their counterparts, although the
      latter results were not routinely statistically significant (p < 0.1). Instructor
      evaluations supported these differences between the two groups.

PMID- 9158544
TI  - The influence of a patient-management course to dental hygiene students on the
      dental anxiety of their patients.
AB  - This study investigated the effect of teaching dental hygiene students a course
      in caregiver-patient relationships on their patients' dental anxiety, and
      patients' feelings toward known anxiety-provoking stimuli. The study group
      (twenty-five men and twenty-five women) was treated by a class of dental hygiene
      students following a behavioral course given after the first visit. The control
      group (twenty-four men, twenty-six women) was treated by another class without
      the intervention. Corah's Dental Anxiety Scale (DAS) and a twelve-item
      questionnaire identifying specific anxiety-provoking situations were completed by
      the patients before initial visit and after the third visit. A significant
      reduction in DAS within the study group was observed after the intervention. In
      both groups, women demonstrated higher anxiety. No significant difference was
      found in the twelve-item questionnaire after intervention in both groups. These
      findings suggest that a four-hour behavioral course to a class of dental hygiene
      students was an influencing factor in reducing their patients' levels of dental
      anxiety.

PMID- 9158545
TI  - New PBL dental curriculum at the University of Adelaide.

PMID- 9158546
TI  - The Faculty Loan Repayment Survey.

PMID- 9158547
TI  - Cytokine production by subsets of CD4 memory T cells differing in P-glycoprotein
      expression: effects of aging.
AB  - We have shown previously that the mouse CD4 memory cell subset can be divided
      into two subpopulations based on differential expression of P-glycoprotein. Cells
      with high levels of P-glycoprotein can be detected by extrusion of the
      fluorochrome Rhodamine 123; they are referred to as R123lo cells. These R123lo T
      cells increase with age and have been shown not to respond to anti-CD3 and IL-2
      by proliferation or IL-4 production. We report here (a) that the failure of the
      R123lo CD4 memory population to respond to anti-CD3/IL-2 stimulation cannot be
      overcome by addition of anti-CD28, PMA, IL-4 or IL-12, alone or in various
      combinations, and (b) that this age-dependent subset exhibits impaired production
      of IL-5 and IL-10 as well as decreased proliferation. R123lo CD4 memory cells
      from young mice are also deficient in IFN gamma secretion by this subset.
      Although the R123lo cells respond poorly to receptor-dependent agonists, they can
      be triggered to proliferate and produce IFN gamma by the combination of PMA and
      ionomycin. In addition to increasing the proportion of R123lo cells in the memory
      CD4 pool, aging also leads to a decline in the ability of R123hi cells to produce
      IL-5 and IL-10. Thus, the accumulation of R123lo cells cannot by itself account
      for the poor proliferation and Th2 cytokine production of aged T cells in
      cytokine-supplemented culture conditions.

PMID- 9158548
TI  - Nitric oxide synthase in rat brain: age comparisons quantitated with NADPH
      diaphorase histochemistry.
AB  - We examined age-related differences in nicotinamide adenine dinucleotide
      phosphate diaphorase (NADPH-d) containing neurons and neuropil in the striatum
      and hippocampus of male Fischer 344 rats at 6, 12, and 26 mo of age. NADPH-d
      staining is considered to be a marker for neurons and neuronal processes
      containing nitric oxide synthase. Rat brains were processed for NADPH-d
      histochemistry and analyzed morphometrically using computerized image analysis.
      The following NADPH-d histochemical parameters were examined: neuronal density,
      neuronal size, and neuropil staining optical density of selected regions. In the
      striatum, significant age-related declines were observed in NADPH-d-positive
      neuronal density and in neuropil staining, while neuronal size increased between
      6 and 12 mo and then declined between 12 and 26 mo. In the hippocampus no
      significant age-related changes were noted in NADPH-d-positive neuronal density
      or size, or in the optical density of the molecular layer of the hippocampal
      dentate gyrus. Thus, age differences in NADPH-d histochemistry appear to be
      regionally specific in the Fischer 344 rat.

PMID- 9158549
TI  - Modulation by food restriction of intracellular calcium signaling in parotid
      acinar cells of aging Fischer 344 rats.
AB  - Previous studies suggest that alpha 1-adrenergic (alpha 1-AR)-induced
      intracellular calcium ([Ca2+]i) mobilization in rat parotid acinar cells declines
      with age. In this study, we examined the effects of food restriction on alpha 1
      AR and muscarinic-stimulated [Ca2+]i mobilization in parotid acinar cells during
      aging. [Ca2+]i levels in response to the alpha 1-AR agonist epinephrine and the
      muscarinic agonist carbachol were evaluated in Fura-2-loaded parotid acinar cells
      from ad libitum-fed (AL) and food-restricted (FR) Fischer 344 male rats at 4, 6,
      14, and 24 months of age. [Ca2+]i responses to epinephrine and carbachol (10
      microM) were significantly reduced (48% and 35%, respectively; p < .05) in cells
      from 24-month-old AL rats as compared to younger AL rats. In contrast, no
      significant reduction of epinephrine and carbachol responses was observed in 24
      month-old FR animals. An age-related increase in basal [Ca2+]i (peak around 14
      months; p < .02) was observed in both AL and FR rats. In addition, basal [Ca2+]i
      was higher in FR than in AL rats at 14 and 24 months of age (p < .02). These
      studies suggest that FR partially attenuates or delays age-related impairments in
      alpha 1-AR- and muscarinic-cholinergic signal transduction systems of parotid
      acinar cells. Basal [Ca2+]i also appears to be altered during aging and by FR.

PMID- 9158550
TI  - Identification of peripheral vascular disease in elderly subjects using optical
      spectroscopy.
AB  - The purpose of this study was to determine the usefulness of near-infrared
      spectroscopy (NIRS) measurements to identify peripheral vascular disease (PVD).
      Usefulness was determined by the frequency of a successful test, as well as
      comparison with standard clinical assessments. Study subjects (N = 117, mean age
      = 67.8 +/- 8.1 yrs) responded to a free screening for PVD. NIRS was used to
      measure the relative O2 saturation of hemoglobin in the soleus muscle. The time
      to 1/2 recovery of O2 saturation (O2T1/2) was measured after 1 minute of repeated
      plantar flexions using a Cybex Eagle seated calf machine. O2T1/2 was used as many
      subjects had recovery curves that did not have an exponential line shape. The
      test was done on both legs and the worst leg was used for analysis. For
      comparative purposes, a clinical history and physical examination were performed
      by a physician or nurse practitioner, which included questions on intermittent
      claudication, examination of peripheral pulses, and questions to identify
      cardiovascular risk factors. NIRS signals were obtained on 105 of 117 subjects
      (89% success rate). Subjects with body mass index (BMI) values above 32 appeared
      to have NIRS O2T1/2 values that were less reliable than subjects with BMI values
      < or = 32 (77% success rate). The O2T1/2 was longer in subjects with claudication
      and reduced pulses than in subjects without these conditions. Sensitivity
      comparing O2T1/2 to claudication and reduced pulse varied from 51-76% and
      specificity from 65-80%, depending on the cutoff value for O2T1/2 that was used
      (normal value plus 1 or 2 SD). A longer O2T1/2 was significantly associated with
      incidence of diabetes, smoking, hypercholesterol, and coronary bypass surgery. In
      summary, successful NIRS O2T1/2 measurements were made in 77% of the subjects,
      with failure primarily occurring in obese subjects. NIRS O2T1/2 measurements
      showed reasonable although not strong agreements with clinical assessment of PVD,
      and with some risk factors for cardiovascular disease.

PMID- 9158551
TI  - Hormone replacement therapy does not augment gains in muscle strength or fat-free
      mass in response to weight-bearing exercise.
AB  - Lower extremity strength and fat-free mass were examined in 58 postmenopausal
      women aged 60-72 yr. Subjects were studied before and after an 11-mo control
      period (n = 16) or before and after an 11-mo weight-bearing exercise training
      program designed to generate relatively high ground reaction forces (n = 42).
      Twenty-two of the exercisers initiated hormone replacement therapy (HRT) at the
      outset of exercise and continued HRT for 11 mo. Hip extension and abduction
      strength were assessed using a hand-held dynamometer. Force production during
      knee extension and flexion was evaluated on an isokinetic dynamometer at 60, 90,
      and 180 degrees/s. Simultaneous knee and hip extension strength was also assessed
      on a leg press machine. Total body and lower extremity fat-free mass were
      determined using dual-energy x-ray absorptiometry. There were no significant
      changes in muscle strength or body composition in control subjects. Both exercise
      groups had significant increases in fat-free mass and in all strength measures.
      Fat-free mass increased from 38.8 +/- 4.3 to 39.7 +/- 4.3 kg in the exercise
      group and from 37.7 +/- 3.9 to 38.9 +/- 4.6 kg in the exercise-plus-HRT group.
      The average relative increase in strength was 16.2 +/- 11.0% in the exercise
      group and 17.0 +/- 13.0% in the exercise-plus-HRT group. Women receiving HRT did
      not have a gain in fat-free mass or in strength over and above that demonstrated
      by the women not on HRT. Our results provide evidence that HRT does not augment
      the increases in muscle mass or strength that occur in response to weight-bearing
      exercise in older women.

PMID- 9158552
TI  - Comparative longevity of pet dogs and humans: implications for gerontology
      research.
AB  - The effect of breed and body weight on longevity in the pet dog was analyzed, and
      a method was developed to standardize the chronological age of dogs in terms of
      physiological time, using human year equivalents. Mortality data from 23,535 pet
      dogs were obtained from a computerized data base of North American veterinary
      teaching hospitals, and the median age at death was determined for pure and mixed
      breed dogs of different body weight. Body size in the dog was inversely related
      to longevity. Within each body weight category, the median age at death was lower
      for pure breed dogs compared with mixed breed dogs. The difference between the
      standardized physiological ages of mixed breed dogs of the same chronological age
      in the smallest and largest body weight categories varied from 8 to > 15 years,
      and between large and small pure breed dogs, the disparity was even greater.
      Laboratory research to explore the biological basis for these breed and body
      weight specific differences in life span among dogs may provide additional clues
      to genetic factors influencing senescence.

PMID- 9158553
TI  - Application of bioelectrical impedance analysis to elderly populations.
AB  - BACKGROUND: Bioelectrical impedance analysis (BIA) can potentially be used to
      estimate body composition in large populations studied at multiple sites.
      However, it is not clear whether age-specific BIA equations are necessary for
      accurate application of BIA to research on elderly subjects. METHODS: We compared
      a published equation designed to predict fat-free mass (FFM) that had been
      derived in a young healthy population (mean age 27 y; mean BMI 23.9 kg/m2), with
      equations that we developed for the elderly by using data from 455 participants
      in the Framingham Heart Study (78 Y; 27.3 kg/m2), using dual-energy x-ray
      absorptiometry (DXA) as a reference technique. The BIA equations were then
      compared in an independent sample of 283 participants in the New Mexico Aging
      Process Study (76 y, 25.5 kg/m2), who also underwent BIA and DXA. RESULTS: When
      the young-population equation was applied to Framingham, it caused an
      overestimation of FFM in heavier subjects that was eliminated by use of the age
      specific equation. However, when the two equations were tested in the New Mexico
      population, the published equation gave estimates of FFM that were closer to DXA
      than the Framingham equations did. CONCLUSIONS: The accuracy of a BIA equation
      depends on the body composition of the population of the population and the
      validation method rather than on age per se. Application of BIA to elderly
      populations requires uniform validation procedures in the actual study
      population, rather than reliance on age-specific equations.

PMID- 9158554
TI  - Validation of multifrequency bioelectrical impedance analysis in monitoring fluid
      balance in healthy elderly subjects.
AB  - BACKGROUND: Multifrequency Bioelectrical Impedance Analysis (MFBIA) is a novel
      method to assess body composition in elderly subjects. However, it is unclear
      whether MFBIA can detect changes in body water compartments in elders. We aimed
      to determine the within-subject variability of MFBIA and the responsiveness to a
      diuretic intervention in aged subjects with a stable fluid balance. METHODS: We
      selected 12 healthy active elderly subjects (5 male, 7 female) with a mean age of
      75 years. Total body water and extracellular fluid (ECF) were measured by
      deuterium oxide- and potassium bromide-dilution techniques. Within-subject
      variability in total body MFBIA was assessed by performing four measurements at
      1, 5, 50, and 100 kHz within a 2-month period. Subsequently, responsiveness of
      MFBIA to the ECF loss caused by oral administration of 40 mg of furosemide was
      determined. RESULTS: Within-subject variability in MFBIA at 1, 5, 50, and 100 kHz
      expressed as standard deviations was 21, 19, 14, and 14 Ohm (omega),
      respectively. Furosemide caused a mean weight loss of 1.8 +/- 0.6 kg, which
      resulted in significant increases in impedance of 57 +/- 24 omega at 1 kHz and 37
      +/- 12 omega at 100 kHz (p < .001). The responsiveness of MFBIA for the diuretic
      intervention was best at 5 kHz (responsiveness index = 1.98). CONCLUSIONS: Within
      subject variability of MFBIA was small in healthy elderly subjects with stable
      fluid balance. Responsiveness of MFBIA to 9% furosemide-induced ECF loss was
      excellent. These data support the necessity for further clinical assessment of
      the value of MFBIA in monitoring fluid balance in geriatric patients.

PMID- 9158555
TI  - Accuracy of nurse aides' functional health assessments of nursing home residents.
AB  - BACKGROUND: Nurse aides provide assessments of nursing home residents' functional
      health for use in care planning and quality assurance. Nurse practitioner
      assessments can serve as a standard for analysis of nurse aides' accuracy. This
      study compared nurse aide to nurse practitioner assessments of nursing home
      residents' functional health with regard to possible bias and extent of
      correlation. METHODS: Nurse aides' accuracy in assessing nursing home residents'
      activities of daily living was evaluated by comparisons to assessments performed
      by a master's-prepared nurse practitioner using four functional assessment
      instruments: the Barthel Index, the Katz Index of Activities of Daily Living, the
      Multidimensional Observation Scale for Elderly Subjects, and the Scaled Outcome
      Criteria. Data were collected in a 159-bed nonprofit nursing home licensed for
      skilled and intermediate care. Residents had a wide variety of functional and
      cognitive abilities and disabilities. Ninety-six nursing home residents provided
      data for the study. Functional health assessments by 24 nurse aides, each
      assessing 4 different nursing home residents, were compared to those of 1 nurse
      practitioner. Statistical analysis of accuracy used paired samples t-tests and
      Pearson product moment correlation coefficients. RESULTS: Nurse aide assessments
      and nurse practitioner assessments were highly correlated. Most functional health
      assessments evidenced no significant nurse aide bias. When bias was present it
      usually resulted from nurse aides electing more optimistic choices when using an
      assessment instrument that offered fewer response levels for rating residents.
      CONCLUSIONS: Nurse aides can accurately use well-calibrated instruments to assess
      nursing home residents' functional health. Demonstration of assessment accuracy
      in nurse aides, who provide the majority of direct care for nursing home
      residents, documented a valuable clinical resource for planning and evaluating
      resident care.

PMID- 9158556
TI  - Successful 6-month endurance training does not alter insulin-like growth factor-I
      in healthy older men and women.
AB  - BACKGROUND: Lean body mass, strength, and endurance decline with advancing age,
      changes paralleled by declines in anabolic hormones, including growth hormone
      (GH) and insulin-like growth factor-I (IGF-I). Acute exercise has been shown to
      stimulate the GH/IGF-I axis, and long-term exercise increases GH. This study
      examined the effect of endurance training on IGF-I in healthy older men and
      women. METHODS: Thirty-one healthy older men (66.9 +/- 1.0 yrs, mean +/- SEM) and
      21 healthy older women (67.1 +/- 1.7 yrs) were randomized to either 3d/wk, 6
      month endurance (ET3) or stretching/flexibility (SF3) protocols. Another group of
      15 healthy older men (69.0 +/- 1.3 yrs) participated in a more intensive 5d/wk, 6
      month endurance protocol (ET5). Before and after training, subjects were weight
      stabilized and participated in maximal exercise tolerance testing, body
      composition assessment, and fasting blood sampling. RESULTS: ET3 training
      resulted in a significant increase (14%) in maximal aerobic power (VO2max),
      significant decreases in body weight (BW), fat mass (FM), and waist/hip ratio
      (WHR), and a significant increase in fat-free mass (FFM). No significant VO2max
      or body composition changes were observed in the SF3 group. For the ET5 group, a
      significant increase (22%) in VO2max and significant decrease in BW, FM, and WHR
      were observed. No significant changes in IGF-I were observed for any of the three
      groups. Pre- versus post-training IGF-I values were very stable (r = .86, p <
      .001) across subjects. CONCLUSIONS: Within-subject basal levels of IGF-I in
      healthy seniors were extremely stable between pre- and post-training assessments.
      Two endurance training protocols of magnitudes sufficient to significantly
      increase aerobic capacity and decrease measures of body adiposity did not
      significantly increase basal levels of IGF-I in healthy older men and women.

PMID- 9158557
TI  - Differences in muscle endurance and recovery between fallers and nonfallers, and
      between young and older women.
AB  - BACKGROUND: Significant morbidity and mortality are associated with falls in
      older adults. We tested the hypothesis that older women with a history of falls
      demonstrate decreased muscle endurance and longer recovery times following
      fatiguing exercise. METHODS: We evaluated dynamic endurance and recoverability of
      the quadriceps femoris of 29 young women (YW) (M age = 21.7), 26 older women with
      a history of falls (FA) (M age = 73.3), and 27 older women with no history of
      falls (NF) (M age = 71.2) using an isokinetic dynamometer. Subjects performed
      repeated maximal concentric knee extensions until the force output of two
      consecutive repetitions fell below 50% of their maximal voluntary contraction
      (MVC). Recovery was defined as the time required for the return of force output >
      or = 80% MVC for 2 consecutive repetitions, within a set consisting of 3 maximal
      contractions. One minute rest was allowed between sets. We collected
      electromyographic (EMG) data from the quadriceps during all testing to evaluate
      spectral shifts. RESULTS: ANOVA with a post-hoc Bonferroni-Dunn test revealed
      time to fatigue was significantly faster in FA than YW (p < .02) and in FA than
      NF (p < .05), but not different between YW and NF. Time to recovery was
      significantly slower in FA than YW (p = .01), but not different between YW and
      NF, or between FA and NF, EMG median frequency power shift (from the beginning to
      the end of the test) was significantly less in FA (p < .001) than either YW (p <
      .002) or NF (p < .05). CONCLUSIONS: Older women with a history of falls
      demonstrate decreased muscular endurance compared to YW and NF, and increased
      time to recover from fatiguing exercise when compared to young women.

PMID- 9158558
TI  - Self-paced resistance training and walking exercise in community-dwelling older
      adults: effects on neuromotor performance.
AB  - BACKGROUND: Resistance-training intervention studies have demonstrated meaningful
      health benefits in older adults; however, most have used exercises performed at
      specific intensities on expensive equipment, which limit their widespread
      applicability. We tested whether two self-paced, less expensive exercise
      protocols could be effective and safe for modifying neuromotor performance and
      functional capacity in community-dwelling adults 65-95 years of age. METHODS: One
      hundred and thirty-one subjects were randomized to a novel resistance training,
      walking, or control group. Subjects determined their level of resistance or
      walking intensity (self-paced) on a session-by-session basis. Muscle strength,
      balance, reaction time, stair climbing speed, and a timed pen pickup task were
      measured before and after the intervention period. Exercisers met three times per
      week for 10 months. RESULTS: Significant improvements in tandem stance and single
      legged stance with eyes open times and stair climbing speed were seen in both
      exercise groups. In addition, resistance trainers improved their muscle strength
      and ability to pick up an object from the floor and reduced the number of
      missteps taken during tandem walking, and walkers reduced tandem walking time.
      Controls showed no significant improvement in any variable. CONCLUSIONS: The two
      self-paced exercise protocols were effective at improving neuromotor performance
      and functional capacity in the study sample and show promise as a safe,
      effective, cost-efficient, acceptable exercise model for primary and secondary
      prevention in the general population of community-dwelling older adults.

PMID- 9158559
TI  - A systematic review of the evidence for hypodermoclysis to treat dehydration in
      older people.
AB  - BACKGROUND: The purpose of the study was to evaluate the evidence supporting the
      use of hypodermoclysis (i.e., subcutaneous infusion of fluids) to treat
      dehydrated elderly patients, and to discuss clinical applications of this mode of
      therapy in the long-term care setting. METHOD: Articles reporting the use of
      hypodermoclysis were identified using a systematic MEDLINE search between January
      1966 and May 1996. Articles were included in our sample if they contained
      original patient data that evaluated either the efficacy or adverse effects
      associated with the use of subcutaneous infusions to treat dehydration in adults,
      whether hyaluronidase was required to facilitate the absorption of subcutaneous
      fluid, or if potassium could be added to the solution. RESULTS: Eighteen articles
      met the inclusion criteria. Since we hypothesized that adverse effects associated
      with hypodermoclysis may have been related largely to the use of nonelectrolyte
      or hypertonic solutions, the studies were evaluated according to the type of
      fluid administered. Six hundred and eighty-five patients were described in 13
      studies evaluating the efficacy and toxicity of subcutaneously administered
      fluid. Four studies evaluated hypodermoclysis using electrolyte-containing
      solutions in 25 patients. Two of these were randomized control trials (RCT) that
      compared hypodermoclysis to intravenous therapy. Both reported similar absorption
      of fluids. In the single RCT that evaluated adverse effects, 4 of 17 patients
      receiving hypodermoclysis reported minor side effects similar to those reported
      with intravenous therapy. Adverse effects were more severe when electrolyte-free
      or hypertonic solutions were evaluated. Of the 639 patients who may have received
      electrolyte-free solutions, 16 patients (2.5%) reported adverse effects, 8 of
      which were severe. Both patients reported to have received hypertonic solutions
      noted adverse effects, one of which was severe. The use of hyaluronidase to
      facilitate absorption was evaluated in 74 patients. These studies suggest that
      hyaluronidase improves the speed of fluid absorption but may not change the
      patient's comfort level. A single case report of 350 subcutaneous infusions in 67
      patients investigated the administration of up to 34 mmol/L of potassium chloride
      (KCl) by hypodermoclysis. The only adverse reaction observed was discomfort at
      the infusion site. CONCLUSIONS: Hypodermoclysis can be used to most safely
      provide fluids when electrolyte-containing fluids are administered.
      Hypodermoclysis may have fallen into disuse because of reports of severe adverse
      reactions related to infusions of electrolyte-free or hypertonic solutions that
      would likely be considered inappropriate today. Whether or not hyaluronidase is
      required to promote subcutaneous fluid absorption remains unresolved. Limited
      evidence suggests that potassium chloride may, with caution, be safely added to
      subcutaneous infusions. The majority of the available studies evaluating
      hypodermoclysis are of poor quality. Because of the tremendous potential benefits
      of administering fluid subcutaneously, there is a need for good quality studies
      to evaluate the efficacy of hypodermoclysis.

PMID- 9158560
TI  - Age-associated changes in blood pressure in a longitudinal study of healthy men
      and women.
AB  - BACKGROUND: Current knowledge of age-associated increases in blood pressure is
      based primarily on unscreened population studies that may not be representative
      of healthy men and women. We examined longitudinal patterns of change in blood
      pressure in healthy male and female volunteers from the Baltimore Longitudinal
      Study of Aging (BLSA). METHODS: Longitudinal mixed-effects regression models are
      used to estimate the age-associated changes in blood pressure in 1307 men (age 17
      97) and 333 women (age 18-93) who have been followed for up to 32 years (mean:
      8.4 years for men and 3.4 years for women) and who have been screened for health
      problems or medications that affect blood pressure. RESULTS: On average, systolic
      pressure is relatively stable in men and women until approximately age 45,
      increases at 5-8 mm Hg per decade in middle age, then accelerates in men and
      stabilizes in women. Diastolic pressure increases at 1 mm Hg per decade at all
      ages in men, whereas in women the rate of change in diastolic pressure increases
      in middle age and then plateaus and may decline after age 70. Additional findings
      include: (a) BLSA cross-sectional and longitudinal findings are more similar than
      has been observed in studies of unscreened samples; (b) there is no evidence of a
      gender cross-over in this group of healthy men and women; and (c) compared to
      previous studies of unscreened samples, healthy BLSA men and women show a weaker
      association between baseline blood pressure and subsequent rate of blood pressure
      change. CONCLUSIONS: These findings suggest that several previously described age
      associated patterns of blood pressure change partially reflect the effects of
      hypertension and its treatment, rather than intrinsic age changes in the blood
      pressure of healthy individuals.

PMID- 9158561
TI  - Self-report versus state records for identifying crashes among older drivers.
AB  - BACKGROUND: There is growing concern about the potential safety implications of
      the increasing number of older drivers. A primary consideration in determining
      risk is the method of outcome ascertainment. In the case of motor vehicle
      crashes, the two most common methods are self-report and state records of events.
      METHODS: The self-report of motor vehicle crashes was compared to state records
      among all active drivers (n = 358) in a representative cohort of community-living
      individuals age 72 years and older in New Haven, Connecticut, in 1989. In the
      baseline interview, participants who reported driving were asked if they had had
      any crashes in the previous year. This was compared to state-recorded crashes
      over the same period. RESULTS: Of the 358 drivers, 33 either reported or had a
      state record of a crash in the previous year. Of the 33, 20 were identified by
      self-report only, 9 by both self-report and state records, and 4 by state records
      only. In the two cases where license reexamination was requested by the officer
      at the scene, both drivers reported the event in the interview. CONCLUSIONS: Self
      report and state records provide complementary information for the ascertainment
      of crashes among older drivers, although in this sample self-report yielded more
      events.

PMID- 9158562
TI  - The retirement adjustment process: changes in the well-being of male retirees
      across time.
AB  - The purpose of this prospective study was to (1) evaluate the impact of
      retirement, (2) monitor the change in adjustment across time, and (3) identify
      the resources predictive of short- and long-term adjustment in retirement. A
      sample of 117 male retirees was assessed on indices of physical and psychological
      health, perceived control, retirement satisfaction, and life satisfaction at 2-4
      months preretirement, 1 year post-, and 6-7 years postretirement. The results
      provided support for a positive impact of retirement, as retirees evidenced
      increases in well-being during the first year. There was also evidence of a
      retirement adjustment process, in that aspects of well-being (i.e., psychological
      health) changed from short- to long-term retirement. Finally, physical health,
      income, and voluntary retirement status predicted short-term adjustment, while
      internal locus of control was an additional resource for long-term adjustment.
      Changes in resources over time also differentially predicted short- and long-term
      adjustment (e.g., an increase in internal locus of control predicted an increase
      in activity satisfaction at 1 year but not at 6-7 years postretirement).

PMID- 9158563
TI  - The interactive effect of perceived control and functional status on health and
      mortality among young-old and old-old adults.
AB  - The effect of perceived control on health has been examined extensively in the
      gerontological literature. A question that has received little attention,
      however, is whether perceived control affords similar benefits to all other
      adults. In a longitudinal study we examined the effect of perceived control, in
      combination with functional status and age, on perceived health, morbidity,
      hospitalization, and mortality. The analyses showed that perceived control
      interacted with functional status for old-old (80+ years old) adults, but not for
      young-old (65-79 years old) adults in terms of perceived health, hospitalization,
      and mortality. For perceived health, feeling in control was of benefit of old-old
      adults with some functional impairment, but not to those with little impairment.
      Moreover, a greater sense of control was associated with lower rates of
      hospitalization and mortality for old-old individuals with little functional
      impairment. These results highlight the usefulness of examining the buffering
      effects of perceived control in relation to different age groups.

PMID- 9158564
TI  - Psychological effects of hearing aid use in older adults.
AB  - Hearing impairment in older adults is a chronic condition with high prevalence
      that shows negative correlations with communication, social integration, well
      being, and cognition. In the present study, a group of elderly individuals with
      mild to moderate hearing loss who received a hearing aid for the first time in
      their lives (aural rehabilitation group, n = 70) and two age-matched control
      groups (hearing-impaired control group without hearing aids, n = 42,
      approximately normal hearing control group, n = 28) were tested longitudinally
      over a 6-month period. Measures examined their performance in the domains of
      communication problems, social activities, satisfaction with social
      relationships, well-being, and cognition. Data analyses show that in older
      persons with mild to moderate hearing loss, hearing aid use has positive effects
      on self-perceived hearing handicap, but there is no effect of hearing aid use in
      domains like social activities, satisfaction with social relations, well-being,
      and cognitive functioning.

PMID- 9158565
TI  - Self-reports on memory functioning in a longitudinal study of the oldest old:
      relation to current, prospective, and retrospective performance.
AB  - Self-evaluation of memory performance, one aspect of metamemory, may be an
      important indicator of concurrent, retrospective, or future decline in memory
      functioning. The relationships among self-evaluations, cognition, and outcome
      were investigated in the OCTO study, a longitudinal, population-based panel of
      the oldest old. Using concurrent data, results indicated that overall cognitive
      ability, depression, gender, and education were associated with self-reports of
      memory for the entire sample. The relation of perception of decline to actual
      decline was also examined. Self-reported decline over a 2-year period was
      associated with actual decline in performance on three tests of memory. Finally,
      self-reported memory function was investigated as an indicator of future
      cognitive decline and diagnosis of dementia. These self-evaluations predicted
      decline on specific tests of memory over 2 years and subsequent diagnosis of
      dementia after 2 and 4 years. The amount of variance accounted for by self
      evaluations, however, was relatively small, suggesting that complaints reflect
      different processes, only one of which is the pathological decline involved in
      dementia.

PMID- 9158566
TI  - Metalinguistic judgments in normal aging and Alzheimer's disease.
AB  - This study compared sentence acceptability judgments from young and healthy older
      adults and older adults with dementia due to probable Alzheimer's disease. Two
      types of sentences were contrasted: one type involved contrasts among verb
      alternations in which semantic distinctions between verbs regulate the
      acceptability of phrase structure variations; the second type involved contrasts
      among directional transformations in which constraints on the movement of noun
      phrases determine the linear order of main and embedded clauses. The primary
      findings were that metalinguistic judgments by healthy older adults as well as
      those with probable Alzheimer's reflected processing demands on working memory.
      In addition, metalinguistic judgments by adults with probable Alzheimer's
      reflected the breakdown of semantic information about verbs.

PMID- 9158567
TI  - Research and politics in policymaking for Social Security.

PMID- 9158568
TI  - The politics of dependency estimates: Social Security Board statistics, 1935
      1939.
AB  - State theorists maintain that Social Security Board (SSB) bureaucrats managed the
      evolution of public welfare. Institutional politics theory more readily accepts
      the influences of political interest groups. SSB archival records offer an
      opportunity to contrast these models and explore the early measurement of old age
      dependency. In reports designed to protect the 1935 Social Security Act, SSB
      staff exaggerated the extent of dependency among elderly persons. By 1939, Board
      statistics clearly showed that children were more impoverished than aged persons.
      SSB leadership did not repudiate prior estimates and they accepted rising
      transfers to aged persons, largely because of the political power of interest
      groups interested in flat pensions. While bureaucrats attempted to control
      events, an institutional politics approach better explains both the pivotal role
      of other, political actors and the solidification of the myth of old age
      impoverishment.

PMID- 9158569
TI  - Age, subjective life expectancy, and the sense of control: the horizon
      hypothesis.
AB  - This article reports a test of the horizon hypothesis, which states that greater
      subjective life expectancy increases the sense of control over one's own life and
      in part accounts for the negative association between age and the sense of
      control. Results of a U.S. survey of 2,029 respondents aged 18 and older (934
      aged 50 and older) support the hypothesis. Subjective life expectancy has a
      significant positive association with the sense of control that does not vanish
      with adjustment for race, sex, education, income, widowhood, inability to work
      because of a disability, physical impairment, and physical fitness. Adjustment
      for subjective life expectancy explains the part of the negative association
      between age and the sense of control that remains after adjustment for education
      and physical impairment. Adjusting the three factors together explains 93.1
      percent of the total association between age and the sense of control, and
      renders the remaining association insignificant.

PMID- 9158570
TI  - Windows to their world: the effect of sensory impairments on social engagement
      and activity time in nursing home residents.
AB  - This study examined relationships between three sensory and communication
      abilities and two areas of nursing home resident behavior. Data from 18,873
      nursing home residents include measures of hearing, visual, and communication
      abilities, and social engagement and time spent in activities. Increasing level
      of visual impairment is associated with low levels of social engagement and low
      time in activities. Both moderate and severe hearing impairment are associated
      with low time in activities, while inadequate communication is associated with
      limits in both social engagement and time in activities. The combined effects of
      visual and communications impairments are associated with low social engagement.
      Increasing attention to sensory and communication losses may lead to improve
      quality of life in this population.

PMID- 9158571
TI  - Rectangularization of the survival curve in The Netherlands: an analysis of
      underlying causes of death.
AB  - This study analyzed the contribution of selected causes of death to
      rectangularization of the survival curve of Dutch men and women above age 60 in
      the 1980s, and determined why rectangularization took place in the 1980s but not
      in the 1970s. The contribution of causes of death was determined by means of a
      decomposition analysis, using mortality data by underlying cause of death, sex,
      and age from Statistics Netherlands. Our results show that mortality reductions
      from ischemic heart disease, cerebrovascular diseases, and lung cancer (men only)
      and mortality increases from chronic obstructive pulmonary diseases (men only)
      and mental disorders (women) contributed to rectangularization in the 1980s.
      Comparison with the 1970s, in addition, demonstrated that in particular changes
      in mortality at advanced ages (i.e., smaller mortality reductions and mortality
      increases) were responsible for the reversal from a decreasingly rectangular
      shape of the survival curve in the 1970s curve to rectangularization in the
      1980s. The combination of increased survival to advanced ages and reduced
      survival at advanced ages explains why rectangularization of the survival curve
      took place recently in The Netherlands.

PMID- 9158572
TI  - Predicting mortality from community surveys of older adults: the importance of
      self-rated functional ability.
AB  - Using data from the 1990 baseline of the National Survey of Self-Care and Aging
      (NSSCA), and nearly three years of follow-up mortality data, we examined the
      association between self-rated functional ability, a global measure of perceived
      ability of function independently, and mortality among a national sample of older
      adults. The study included 3,485 subjects selected from the Medicare Beneficiary
      Files according to a stratified random sampling design, with approximately equal
      numbers of adults by gender in each of three age categories, 65-74, 75-84, and 85
      and over. Self-rated functional ability was found to have an independent
      contribution to the subsequent risk of death among older adults. Using
      multivariate models that accounted for self-rated health, age, gender, medical
      conditions, functional status, and assistance from others, poor self-ratings on
      this single item nearly doubled the risk of death during the follow-up period.
      These findings suggest the importance, for both researchers and clinicians, of
      measuring the potential prognostic importance of self-ratings of health and self
      ratings of functional ability among older adults.

PMID- 9158573
TI  - A randomized trial of group outpatient visits for chronically ill older HMO
      members: the Cooperative Health Care Clinic.
AB  - OBJECTIVE: To compare the impact of group outpatient visits to traditional
      "physician-patient dyad" care among older chronically ill HMO members on health
      services utilization and cost, self-reported health status, and patient and
      physician satisfaction. DESIGN: A 1-year randomized trial. SETTING: A group model
      HMO in the Denver Metropolitan area. PARTICIPANTS: Three hundred twenty-one
      members aged 65 and older, randomized to a group visit intervention (n = 160) or
      to usual care (n = 161). INTERVENTION: Patients with high health services
      utilization and one or more chronic conditions had monthly group visits with
      their primary care physician and nurse. Visits included health education,
      prevention measures, opportunities for socialization, mutual support, and for one
      to-one consultations with their physician, where necessary. MEASUREMENTS: Health
      services utilization and associated cost, health status, and patient and
      physician satisfaction. RESULTS: Outcome measures obtained after a 1-year follow
      up period showed that group participants had fewer emergency room visits (P =
      .009), visits to subspecialists (P = .028), and repeat hospital admissions per
      patient (P = .051). Group participants made more visits (P = .021) and calls (P =
      .038) to nurses than control group patients and fewer calls to physicians (P =
      .019). In addition, a greater percentage of group participants received influenza
      and pneumonia vaccinations (P < .001). Group participants had greater overall
      satisfaction with care (P = .019), and participating physicians reported higher
      levels of satisfaction with the groups than with individual care. No differences
      were observed between groups on self-reported health and functional status. Cost
      of care per member per month was $14.79 less for the group participants.
      CONCLUSIONS: Group visits for chronically ill patients reduce repeat hospital
      admissions and emergency care use, reduce cost of care, deliver certain
      preventive services more effectively, and increase patient and physician
      satisfaction.

PMID- 9158574
TI  - Transitions in health care use and expenditures among frail older adults by
      payor/provider type.
AB  - OBJECTIVES: To assess whether transitions in health care expenditures differed
      over time by payor/provider type: Medicare fee-for-service (FFS), Medicaid
      Medicare, and Medicare HMO. DESIGN: Longitudinal study. SETTING: A large,
      nonprofit healthcare system in San Diego, California. PARTICIPANTS: A total of
      450 frail older people who responded to the baseline and follow-up surveys and
      who survived the 18-month study period. MEASUREMENTS: Measures included three
      total expenditure categories for each 6-month period: low users (< $4000); medium
      users ($4000-$19,999); or high users ($20,000+). Seven conceptually meaningful
      expenditure trajectories over time were identified: (1) consistently low
      expenditures, (2) consistently medium expenditures, (3) consistently high
      expenditures, (4) decreasing expenditures, (5) increasing expenditures, (6) U
      shaped expenditures, and (7) inverted U-shaped expenditures. MAIN RESULTS:
      Logistic regression analyses showed that HMO enrollees were about twice as likely
      as Medicaid-Medicare beneficiaries to have consistently low expenditures, but no
      differences were found between the FFS and HMO groups on this trajectory. Other
      expenditure patterns showed no significant differences by payor/provider group.
      Significant interactions among payor/provider type, low/medium/ high expenditure
      status, and time were observed for inpatient hospital care, skilled
      nursing/rehabilitation care, and home health care. CONCLUSION: This study
      illustrates the complexity of frail older people with respect to their health
      care expenditures and service use. Expanded efforts to control health care
      expenditures for frail older people should focus first on those who are dually
      enrolled. In addition, because mean medical expenditures for high users enrolled
      in different payor/ provider groups were surprisingly similar, the data suggest
      that containing expenditures for individuals in the highest usage group
      ($20,000+) presents challenges for physicians practicing in an era of healthcare
      reform, regardless of payor/ provider setting.

PMID- 9158575
TI  - The sequelae of hospitalization for congestive heart failure among older adults.
AB  - OBJECTIVES: To estimate the independent effect of hospitalization for congestive
      heart failure (CHF) on subsequent mortality, readmission for CHF,
      rehospitalization for any reason, and change in functional status. DESIGN:
      Secondary analysis of the nationally representative Longitudinal Study on Aging,
      Baseline (1984) interview data are linked to Medicare hospitalization and death
      records for 1984-1991 and to functional status reports at three biennial follow
      ups. SETTING: In-home and telephone interviews. PARTICIPANTS: a total of 7527
      noninstitutionalized older adults aged 70 years or older at baseline.
      MEASUREMENTS: Hospitalization for CHF was defined as having one or more episodes
      with primary or secondary discharge ICD9-CM codes of 428. Multivariable
      proportional hazards, logistic and linear regression, as well as multiple
      classification analysis, were used to estimate the independent effects of having
      been hospitalized for CHF. RESULTS: The adjusted risk ratios for having a primary
      or secondary hospital discharge diagnosis of CHF on mortality (compared with not
      having any CHF hospital discharge diagnoses) were 1.58 (CI95% = 1.40 to 1.78) and
      1.29 (CI95% = 1.15 to 1.45), respectively (P < .001). CHF readmission and
      rehospitalization rates were substantial, ranging from 16.0 to 47.5% at 1 year,
      depending on the criteria employed. The adjusted odds ratios for having any
      subsequent hospitalizations associated with having a primary or secondary
      hospital discharge diagnosis of CHF (compared with not having any CHF hospital
      discharge diagnoses) were 7.70 (CI95% = 6.20 to 9.57) and 2.99 (CI95% = 2.51 to
      3.56), respectively (P < .001). The percent increases in the number of hospital
      episodes, total charges, and total length of stay attributable to having been
      hospitalized for CHF were significant (P < .001) and ranged from 15.5 to 66.7%.
      Having been hospitalized for CHF was also related significantly to greater
      increases in the mean number of functional limitations at follow-up. CONCLUSION:
      Hospitalization for CHF among older adults increases substantially the risk of
      subsequent mortality, readmission for CHF, rehospitalization for any reason, and
      greater functional decline. Therefore, greater attention to the prevention and
      management of CHF is needed.

PMID- 9158576
TI  - Rising from the floor in older adults.
AB  - OBJECTIVE: The primary goal was to determine the ability of older adults to rise
      from the floor. A secondary goal was to explore how rise ability might differ
      based on initial body positions and with or without the use of an assistive
      device. DESIGN: Cross-sectional analysis of young, healthy older, and congregate
      housing older adults. SETTING: University-based laboratory and congregate housing
      facility. PARTICIPANTS: Young adult controls (12 men and 12 women, mean age 23
      years), healthy older adults (12 men and 12 women, mean age 73 years), and
      congregate housing older adults (32 women and 6 men, mean age 80 years). The
      healthy older adult women (n = 12, mean age 75 years) and a subset of the
      congregate housing women (n = 27, mean age 81 years) were identified for further
      analyses. INTERVENTION: Videotaping and timing of rising from the floor from
      controlled initial body positions (supine, on side, prone, all fours, and
      sitting) and with or without the use of a furniture support. MAIN OUTCOME
      MEASURES: Whether subjects were successful in rising, and if they were, the time
      taken to rise. Subjects also rated their perceived difficulty of the task as
      compared to the reference task, rising from a supine position. RESULTS: Older
      adults have more difficulty rising from the floor than younger adults. The
      healthy old took twice as long as the young to rise, whereas the congregate old
      took two to three times as long as the healthy old to rise. Although all young
      and healthy old rose from every position, a subset of the congregate housing
      residents was unable to rise from any position, 24% when attempting to rise
      without a support and 13% when attempting to rise with a support. Congregate old
      were most likely to be successful when rising from a side-lying position while
      using the furniture for support. The more able congregate old, as well as the
      young and healthy old, rose more quickly and admitted to the least difficulty
      when rising from the all fours position. CONCLUSIONS: The inability to rise from
      the floor is relatively common in congregate housing older adults. Based on the
      differences between groups in time to complete the rise, determining the
      differences in rise strategies, and the underlying biomechanical requirements of
      rising from different positions with or without a support would appear to be
      useful. These data may serve as the foundation for future interventions to
      improve the ability to rise from the floor.

PMID- 9158577
TI  - Depression without sadness: functional outcomes of nondysphoric depression in
      later life.
AB  - OBJECTIVES: We hypothesized that depressive symptoms not meeting full standard
      criteria for Major Depression would be associated with significant functional
      impairment among older adults over the course of a 13-year follow-up interval.
      Specifically, we developed criteria for a form of depression whose core symptoms
      did not include sadness or dysphoria. DESIGN: Population-based 13-year follow-up
      survey. SETTING: Community-dwelling adults living in East Baltimore in 1981.
      PARTICIPANTS: Subjects were the 1612 participants of the Baltimore sample of the
      Epidemiologic Catchment Area Program aged 50 years and older at the initial
      interview in 1981. MEASUREMENTS: The subjects were sorted into four categories
      based on their responses at baseline: (1) persons meeting standard criteria for
      Major Depression; (2) persons meeting alternative criteria for depression with
      dysphoria or (3) without dysphoria; and (4) a comparison category of persons not
      meeting any criteria for depression ("noncases"). The mortality and functional
      status of each group were compared after a 13-year follow-up interval. RESULTS:
      Compared with non-cases, participants aged 50 years and older who reported
      depressive symptoms but who denied sadness or dysphoria (nondysphoric depression)
      were at increased risk for death (relative risk (RR) = 1.70; 95% confidence
      interval (CI) (1.09, 2.67)), impairment in activities of daily living (RR = 3.76;
      95% CI (1.73, 8.14)), impairment in instrumental activities of daily living (RR =
      5.07; 95% CI (2.24, 11.44)), psychologic distress (RR = 3.68; 95% CI (1.47,
      9.21)), and cognitive impairment (RR = 3.00; 95% CI (1.31, 6.89)) after a 13-year
      follow-up interval. The findings were not wholly explained by potentially
      influential baseline characteristics such as age, education, selected comorbid
      medical conditions, and functional status. CONCLUSION: Among adults aged 50 years
      and older, nondysphoric depression may be as important as Major Depression in
      relation to the development of functional disability and other long-term
      outcomes.

PMID- 9158578
TI  - Frontotemporal dementia versus vascular dementia: differential features on mental
      status examination.
AB  - OBJECTIVE: After Alzheimer's disease, vascular dementia (VaD) and frontotemporal
      dementia (FTD) are among the most common dementing illnesses. FTD may have a
      neuropsychological profile similar to that of VaD, and patients with these
      dementias may be difficult to distinguish on clinical examination. The purpose of
      this study was to elucidate distinct cognitive profiles of a large group of FTD
      and VaD patients on a brief, clinical mental status examination. DESIGN: A
      comparison of 39 FTD patients and 39 VaD patients on a brief, clinical mental
      status examination. SETTING: A Dementia Research Center and affiliated,
      university hospitals. METHODS: The FTD patients were diagnosed by noncognitive
      clinical and neuroimaging criteria, and the VaD patients met NINDS-AIREN criteria
      for vascular dementia. The two dementia groups were comparable on three dementia
      assessment scales. MEASUREMENTS: The mental status measures included the
      neuropsychological battery from the Consortium to Establish a Registry for
      Alzheimer's Disease (CERAD), plus supplementation from the Neurobehavioral
      Cognitive Status Examination (NCSE) for cognitive areas not assessed by the
      CERAD). RESULTS: The FTD and VaD groups differed significantly on the mental
      status examination measures. FTD patients performed significantly better than the
      VaD patients on digit span and constructions, despite comparable performance by
      both groups on calculations. Although not statistically significant, the FTD
      group performed worse than the VaD group on verbal fluency and abstractions.
      These differences were not explained by group differences in age and education.
      CONCLUSION: These results suggest that cognitive differences between FTD and VaD
      groups reflect greater frontal pathology in contrast to relative sparing of
      posterior cortex and subcortical white matter in FTD. These cognitive differences
      as measured by a mental status examination may help distinguish between these two
      dementia syndromes.

PMID- 9158579
TI  - Cognitive markers preceding Alzheimer's dementia in the healthy oldest old.
AB  - OBJECTIVE: To look for preclinical markers of Alzheimer's dementia in a sample of
      healthy, oldest old individuals. DESIGN: Prospective, longitudinal study of
      individuals examined at yearly intervals with neuropsychological tests selected
      to be sensitive to the early detection of dementia. PARTICIPANTS: One hundred and
      thirty-nine community-dwelling, functionally independent, healthy individuals 65
      to 106 years of age who met strict criteria for lack of dementia at entry.
      Incident dementia cases consisted of 16 volunteers all 80 years old or older who
      developed dementia of the Alzheimer's type and 31 volunteers 80 years old and
      older showing no evidence of dementia during a mean 2.8-year follow-up interval.
      MEASUREMENTS: Scores on 10 neuropsychological measures were analyzed for the
      initial examination when none of the volunteers showed clinical evidence of
      dementia and for the two subsequent yearly examinations. RESULTS: Individuals who
      subsequently developed dementia showed evidence of verbal memory impairment at
      their initial examination, which was a mean of 2.8 years before clinical evidence
      of dementia. The average yearly incidence rate for dementia in those 80 years of
      age and older was 12%. Performance of individuals who did not development
      dementia remained relatively stable during follow-up for up to 5 years.
      CONCLUSION: Alzheimer's disease has a preclinical stage in which verbal memory
      decline is the earliest sign. Dementia in the oldest old is distinguishable from
      age-related cognitive decline.

PMID- 9158581
TI  - Does aging mean a better life for women?
AB  - OBJECTIVE: To study 10-year changes in selected quality of life dimensions in a
      cohort of aging Eastern Finnish women. DESIGN: Ten-year follow-up of a
      representative population sample. SETTING: The county of Kuopio in Eastern
      Finland. PARTICIPANTS: In 1982, a representative sample (n = 296) of 50 to 60
      year-old women was examined in the FIN-MONICA study. Ten years later, 241 of the
      participants were re-examined. MEASUREMENTS: Self-administered questionnaires
      were used to collect the data. Self-rated health, self-rated physical fitness,
      frequency of leisure time physical activity, functional capacity, reported
      symptoms, occurrence of diseases, and satisfaction with family life and economic
      situation were measured. In 1992, total life satisfaction at that moment and 5
      years earlier were also assessed. RESULTS: The self-rated health assessment
      remained unchanged. During the 10 years from 1982 to 1992, the proportion of
      women who reported diagnosed cardiopulmonary diseases increased; angina pectoris,
      in particular, increased from 6% to 20%. However, even though their running
      ability had decreased, the number of women rating their physical fitness as good
      or fairly good increased from 23% to 32%. The participants reported significantly
      less headache and feelings of exhaustion than they had 10 years earlier. Average
      satisfaction with their economic situation increased, and satisfaction with
      family life remained the same. Thirty-seven percent of the women rated their
      current life situation as better than 5 years previously, 29% felt that it had
      remained the same, and 34% indicated that it had become worse during the past 5
      years. CONCLUSION: These data suggest that some quality of life dimensions may
      improve during aging in postmenopausal women.

PMID- 9158580
TI  - Oral staphylococcus in older subjects with rheumatoid arthritis.
AB  - OBJECTIVE: To determine if Staphylococcus aureus and Staphylococcus epidermidis,
      etiologic bacterial agents to late prosthetic joint infections (LPJI), are more
      prevalent in the oral flora of older individuals with rheumatoid arthritis (RA)
      than in an age and gender-matched nonarthritic control population (NA). DESIGN:
      Cultures were obtained from the nares, oropharynx, saliva, tongue, and gingival
      crevice, and the results were compared between older patients with RA and
      controls. SETTING: University of Michigan Medical Center, Ann Arbor, VA Medical
      Center, and University of Michigan School of Dentistry. PARTICIPANTS: A total of
      111 community-dwelling subjects with a diagnosis of RA and 83 gender-matched
      control subjects. MEASUREMENTS: Colistin nalidixic acid agar plates with 5%
      sheep's blood were inoculated and incubated. Isolates were speciated using the
      API Staph Trac micro method and catalase and coagulase tests. MAIN RESULTS:
      Individuals with RA had a higher prevalence of S. aureus isolated from the oral
      cavity. However, only the oropharynx and tongue revealed higher rates; all other
      sites were insignificant. The presence of oral S. aureus was associated with
      xerostomia. Staphylococcus epidermidis was not detected from any of the oral
      sites sampled. Sixty-two percent (10/16) of the S. aureus isolates from the RA
      subjects were resistant to penicillin and ampicillin, whereas none were resistant
      to a cephalosporin. CONCLUSIONS: These findings suggest that rheumatoid arthritis
      may be a risk factor for LPJI in older prosthetic joint patients undergoing
      invasive dental procedure in the posterior oral cavity. This increased risk is
      caused, in part, by a higher prevalence of S. aureus in the posterior oral
      cavity. The prevalence and the antibiotic resistance of S. aureus must be
      considered when determining the need for chemoprophylaxis.

PMID- 9158582
TI  - Seasonal prevalence of vitamin D deficiency in institutionalized older adults.
AB  - OBJECTIVE: To determine the prevalence and seasonal variation of vitamin D
      deficiency among older residents of long-term care facilities. DESIGN: Cross
      sectional survey with 6-month follow-up. SETTING: Three long-term care facilities
      in Toronto. PATIENTS: Persons more than 65 years old, medically stable, who had
      resided in the facility for at least 6 months and had no conditions known to
      interfere with vitamin D metabolism. MEASUREMENTS: Information regarding
      demographics, past health, and medication use was collected. Mental and
      functional status were assessed by questionnaire. Venous blood samples were
      analyzed for alkaline phosphatase, calcium profile, albumin, intact parathyroid
      hormone, 25 hydroxyvitamin D (25OHD), and vitamin D binding protein in September
      1994 and March 1995. In a subgroup of patients, bone specific alkaline
      phosphatase was measured, and dietary intake of vitamin D was assessed. RESULTS:
      A total of 155 subjects completed the study. The mean age of the subjects was
      83.2 years (SD 7.1), and 47% were female. The mean 25OHD level in the March
      sample (39.9 nmol/L, SD 19.7) was significantly lower than the mean 25OHD level
      in the September sample (44.9 nmol/L, SD 16.9) (P = .001). The prevalence of
      vitamin D deficiency in the osteomalacic range (25OHD < 25 nmol/L) increased from
      9% in the fall sample to 18% after the winter (chi 2 = 4.65, P = .03). The
      prevalence of borderline deficiency or hypovitaminosis D (25OHD < 40 nmol/L)
      increased from 38% in the fall sample to 60% in the spring sample (chi 2 = 14.9,
      P < .001). Dependence in transfers was associated with an increased risk of
      hypovitaminosis D, odds ratio 2.08 (95% confidence interval 1.08-4.01),
      dependence in ambulation 2.57 (1.26-5.23), and regular use of a wheelchair 2.17
      (1.09-4.31). When entered into a forward conditional logistic regression model,
      only dependence in ambulation remained significant, with an adjusted odds ratio
      of 2.57 (95% CI: 1.26-5.18). CONCLUSIONS: Vitamin D deficiency and borderline
      vitamin D status are common among older residents of long-term care facilities in
      Canada. Even though this population has limited outdoor exposure, seasonal
      variation in the prevalence of deficiency remains significant. Evaluation of
      interventions to improve the status of vitamin D nutrition in this population is
      needed.

PMID- 9158583
TI  - Identifying hospitalized older patients at varying risk for physical performance
      decline: a new approach.
AB  - OBJECTIVE: A classification tree analysis identifies patient groups at varying
      risk for decline in physical performance 1 year after hospitalization. DESIGN:
      Prospective cohort study. SETTING: Tertiary care VAMC. PARTICIPANTS: A total of
      507 acutely ill hospitalized male veterans aged 65 years and older. MEASUREMENTS:
      Eighteen admission characteristics were considered as potential predictors:
      demographic data, medical diagnoses, functional status (e.g., ADL and IADL),
      geriatric conditions (e.g., incontinence, vision impairment, weight change),
      mental status, depression, and physical functioning (measured by self-report (MOS
      PFR) and the Physical Performance and Mobility Examination (PPME)). Outcome
      measure was change in PPME status at 12-months post-admission. RESULTS: Patients
      with the greatest risk for decline had both high baseline physical performance
      (PPME > or = 9) and at least moderate self-report limitations on physical
      functioning (MOS-PFR < or = 36, mean = 30.8). Patients with the lowest risk of
      decline had impaired baseline physical performance (PPME < or = 8) but fewer self
      report limitations on physical functioning (MOS-PFR > or = 31, mean = 37.4) and
      two or less geriatric conditions. CONCLUSIONS: The predictive role of self-report
      functioning suggests that perception of the impact of health on one's own
      physical functioning is associated with future performance. The number of
      geriatric conditions is also an important predictor of physical performance
      change. By identifying patient risk groups based on geriatric conditions,
      physical performance, and self-report physical functioning, future targeting
      strategies may improve physical performance outcomes for hospitalized older
      adults.

PMID- 9158584
TI  - Increased coronary heart disease mortality after the Hanshin-Awaji earthquake
      among the older community on Awaji Island. Tsuna Medical Association.
AB  - OBJECTIVES: To investigate the characteristics of earthquake (EQ)-induced
      coronary heart disease (CHD) deaths. SETTING AND PARTICIPANTS: On January 17,
      1995, the south part of Hyogo Prefecture in Japan was struck by a major EQ
      (Hanshin-Awaji EQ) measuring 7.2 on the Richter scale. We investigated the
      characteristics of EQ-induced CHD deaths (myocardial infarction and sudden death)
      in the Tsuna region, which is a community with a large older population (31% of
      the total of 64,000 residents are 60 years of age or older) and includes the
      epicenter and one of the most heavily damaged areas. MEASUREMENTS: EQ-related CHD
      mortality on the basis of direct access to records of physicians who were able to
      continue services for the EQ victims without interruption by this disaster
      situation. RESULTS: Coronary heart disease deaths increased for a few months
      after the EQ, and the total number from January 17 to April 30, 1995, was 45,
      which was significantly (1.5 times) higher than the 31 deaths during the same
      period of the previous year (1994). The CHD deaths after the EQ all occurred in
      individuals more than 60 years of age and had a positive correlation with EQ
      induced damages. Concerning the onset time, CHD deaths occurred 1.8 times more
      often (P < .05) in the nighttime (11 PM to 5 AM) and 1.4 times as often during
      the morning (5 AM to 11 AM), whereas their occurrence did not vary during a 12
      hour period from 11 AM to 11 PM. CONCLUSION: Deaths of older individuals from CHD
      persisted for a few months after the EQ and were especially prominent during the
      nighttime and morning. Reduction of stress and related coronary risk factors in
      this period may suppress CHD deaths after a major EQ.

PMID- 9158585
TI  - Predictive validity of the Pra instrument among older recipients of managed care.
AB  - OBJECTIVE: To determine the validity of the Pra instrument in predicting the use
      of health-related services by older enrollees in a managed care plan. DESIGN:
      Cohort study. At baseline, a survey was administered by mail. Responses were
      entered into the Pra formula to estimate each person's probability of using
      health-related services heavily in the future. The subjects' use of services
      during the following year was monitored through claims submitted to their managed
      care organization. SETTING: Urban and suburban areas of Southern California.
      PARTICIPANTS: Persons aged 65 years and older enrolled in a Medicare risk health
      plan (n = 6802). MEASUREMENTS: Baseline data included demographic, health
      related, social, functional, and previous-use-of-service characteristics. Follow
      up data included the use of and claims for payment for inpatient hospital care,
      emergency room services, nursing home services, home care, ambulance services,
      outpatient surgery, and durable medical equipment. RESULTS: High-risk subjects
      (highest quartile of Pra values) incurred hospital admissions and claims that
      were 2.5 and 2.7 times greater than those of low-risk subjects (lower three
      quartiles). CONCLUSIONS: The Pra formula is recommended for screening older
      adults enrolled in managed care organizations (as well as for screening those in
      the fee-for-service environment). It identifies older people who may benefit from
      interventions designed to avert health crises and the need for expensive care.

PMID- 9158586
TI  - Using administrative databases to evaluate long-term care.

PMID- 9158587
TI  - Implementation of health care guidelines for older persons is being delayed.

PMID- 9158588
TI  - The Health Advisory Service.

PMID- 9158589
TI  - Efforts to improve primary care delivery to nursing home residents.
AB  - OBJECTIVE: To describe a primary care practice model used by health maintenance
      organizations (HMOs) that serve medicare beneficiaries to improve the provision
      of primary care to nursing home residents. PARTICIPANTS: Medicare beneficiaries
      who reside in nursing homes and who are enrolled in HMOs. CONCLUSION: Several
      HMOs are using physician-nurse practitioner teams to provide primary care to
      nursing home residents. The potential to improve the delivery of these services
      in nursing homes, particularly to long-stay residents, is apparent. However,
      obstacles arise in developing this practice model in HMOs, including difficulty
      recruiting both nurse practitioners and physicians and the lack of HMO-based
      research on the effects of such a model.

PMID- 9158590
TI  - Speech perception in older adults: the importance of speech-specific cognitive
      abilities.
AB  - OBJECTIVE: To provide a critical evaluation of studies examining the contribution
      of changes in language-specific cognitive abilities to the speech perception
      difficulties of older adults. DESIGN: A review of the literature on aging and
      speech perception. CONCLUSIONS: The research considered in the present review
      suggests that age-related changes in absolute sensitivity is the principal factor
      affecting older listeners' speech perception in quiet. However, under less
      favorable listening conditions, changes in a number of speech-specific cognitive
      abilities can also affect spoken language processing in older people. Clinically,
      these findings suggest that hearing aids, which have been the traditional
      treatment for improving speech perception in older adults, are likely to offer
      considerable benefit in quiet listening situations because the amplification they
      provide can serve to compensate for age-related hearing losses. However, such
      devices may be less beneficial in more natural environments, (e.g., noisy
      backgrounds, multiple talkers, reverberant rooms) because they are less effective
      for improving speech perception difficulties that result from age-related
      cognitive declines. It is suggested that an integrative approach to designing
      test batteries that can assess both sensory and cognitive abilities needed for
      processing spoken language offers the most promising approach for developing
      therapeutic interventions to improve speech perception in older adults.

PMID- 9158591
TI  - Integrating geriatrics into the subspecialties of internal medicine: the Hartford
      Foundation/American Geriatrics Society/Wake Forest University Bowman Gray School
      of Medicine Initiative.

PMID- 9158592
TI  - Integrating geriatrics into cardiology training programs.

PMID- 9158593
TI  - Managed care: good medicine for old people?

PMID- 9158594
TI  - Protecting older people while managing their care.

PMID- 9158595
TI  - Physician-assisted suicide in Alzheimer's disease.
AB  - This paper takes up the question of physician-assisted suicide (PAS) in
      Alzheimer's disease (AD), reviewing arguments for and against in a broad
      interdisciplinary context. Preemptive PAS-AD involving competent patients raises
      the further question of AD-euthanasia. The author concludes, after thorough
      assessment of the literature, that caution in moving toward AD-PAS is necessary.
      However, where PAS is legalized, it may be difficult to justify precluding people
      with AD from access.

PMID- 9158596
TI  - Chronic constipation: a clinical conundrum.

PMID- 9158597
TI  - Non-insulin-dependent diabetes mellitus and Alzheimer's disease.

PMID- 9158598
TI  - Nicotinic system and Alzheimer's disease.

PMID- 9158599
TI  - Pandora's pillbox.

PMID- 9158600
TI  - Medical costs for older people are not unfairly spent.

PMID- 9158601
TI  - Neutrophil hypersegmentation may unmask vitamin B12 deficiency in patients with
      normal serum B12 levels.

PMID- 9158602
TI  - Metabolic complications in tuberculosis patients: the disease or the treatment?

PMID- 9158603
TI  - A case of acute idiopathic pericarditis with rapid relapse and cardiac tamponade
      in an older woman.

PMID- 9158604
TI  - The 'safety net' and other myths. It's time to challenge our cherished illusions.

PMID- 9158605
TI  - Get the most from your browser. And fly, don't crawl, through the Web.

PMID- 9158606
TI  - Headache as a symptom of ominous disease. What are the warning signals?
AB  - Headache can be an invaluable premonitory signal of imminent subarachnoid
      hemorrhage and cerebral infarction and can herald the onset of ominous and
      sometimes elusive disorders (arterial dissection, encephalitis, systemic and
      central vasculitides, and cerebral venous thrombosis) which have the potential
      for neurologic catastrophe and are often not obvious on routine CT brain imaging.
      Only rarely does serious underlying disease give rise to a headache that exactly
      mimics a migraine or tension headache. Inevitably, there are atypical features or
      warning signals. A limited number of serious causes for headache which may be "CT
      negative" should be considered in patients with "red flag" manifestations, such
      as seizures and cognitive changes. These should prompt further investigation with
      MRI and/or lumbar puncture.

PMID- 9158607
TI  - Menstrual migraine. Methods of prevention and control.
AB  - In many women, migraine headaches are clearly linked to estrogen levels: the
      incidence rises at the menarche; attacks may be precipitated by falling estrogen
      levels before menses; and symptoms usually improve during pregnancy when there
      are noncyclic high levels of estrogen. Decreased estrogen production in the
      perimenopausal phase may trigger an exacerbation of migraine. However, after
      menopause when estrogen levels are noncyclic and low, there may be an improvement
      in migraine. The falling estradiol level rather than the absolute level provides
      the trigger for menstruation-associated migraine. Treatment involves both
      prophylactic and acute measures. Therapy for an acute attack is similar to that
      for nonmenstrual migraine. Sumatriptan is equally effective for both nonmenstrual
      and menstrual migraine.

PMID- 9158608
TI  - Headaches in children. When is a complete diagnostic workup indicated?
AB  - Migraines, migraine variants, and other headache types often present for the
      first time during childhood; they require follow-up and, when appropriate,
      further investigation. Management of migraine should include a discussion of
      therapeutic goals with patients and parents. Appropriate medications are limited
      in younger children, but older children and adolescents have more options, such
      as the new serotonin-agonist agents (eg, sumatriptan succinate), which are now
      undergoing study for use in this age-group. Preventive therapy, both
      nonpharmacologic and pharmacologic, should be described to patients and parents
      so they understand the options available if headaches recur.

PMID- 9158609
TI  - Headaches in older people. How are they different in this age-group?
AB  - The cause of headaches in older people is more likely to be disease than in
      younger people. Therefore, a high index of suspicion and a willingness to
      investigate new headaches in the elderly are essential. Benign dysfunctional
      headaches (eg, migraine, tension-type headaches) that have carried over from
      youth are found most often. However, several diseases with increased prevalence
      in the elderly can cause headaches, including giant cell arteritis, intracranial
      mass lesions, ischemic cerebrovascular disease, and chronic obstructive lung
      disease with hypercapnia. Unfortunately, many prescription and over-the-counter
      drugs being taken for medical diseases commonly found in aging patients can cause
      headaches. Hypnic headaches are an unusual but easily recognized and treated
      problem found only in the elderly.

PMID- 9158610
TI  - Allergic rhinitis. Recognizing signs, symptoms, and triggering allergens.
AB  - Runny noses, sneezing, nasal congestion, and other nuisance symptoms are part and
      parcel of primary care practice. But how can you quickly discern which symptoms
      are related to common colds and which stem from allergic rhinitis? Careful
      history taking usually provides clues, but allergy testing may be needed when
      triggers are not clear. In this first of two articles on allergic rhinitis, Dr
      Ferguson explains what to look for, what questions to ask, when to test for
      allergies, and how to modify a patient's environment to minimize problems. The
      second article, beginning on page 117, discusses pharmacologic treatment and
      immunotherapy for allergic rhinitis.

PMID- 9158611
TI  - Allergic rhinitis. Options for pharmacotherapy and immunotherapy.
AB  - A trial of allergy medication can be both diagnostic and therapeutic in a patient
      with suspected allergic rhinitis, but with so many treatment options, it is
      sometimes difficult to know where to start. In this second of two articles on
      allergic rhinitis, Dr Ferguson provides information on efficacy and costs for
      various allergy drugs and discusses when to consider immunotherapy. The first
      article, beginning on page 110, discusses signs, symptoms, and triggering
      allergens.

PMID- 9158612
TI  - Benign prostatic hyperplasia in elderly men. What are the special issues in
      treatment?
AB  - BPH is an age-related condition that can give rise to urinary symptoms. As the
      proportion of elderly men in the population rises, the number with symptomatic
      BPH requiring advice on possible treatments will increase. A range of effective
      treatments is available, and although there are certain absolute indications for
      surgery, patients with moderate or severe symptoms require counseling to reach a
      decision on the treatment modality most appropriate for them. Concomitant age
      related disease and use of multiple medications add to the complexity of treating
      elderly men for BPH. In every case of BPH, the risks of each treatment option
      should be weighted against the potential benefits and a joint decision reached by
      physician and patient.

PMID- 9158613
TI  - Lipid screening in adults. Working to prevent coronary artery disease. Institute
      for Clinical Systems Integration.

PMID- 9158614
TI  - Acute red eye. Differentiating viral conjunctivitis from other, less common
      causes.
AB  - Adenoviral conjuctivitis is one of the most common causes of acute red eye. Other
      diagnostic considerations include herpes virus conjunctivitis, chlamydial
      conjunctivitis, allergic conjunctivitis, and various other less common
      infections. Careful history taking can help in identifying a viral cause. The
      presentation may range from a minor conjunctivitis resulting from an upper
      respiratory tract infection to a serious, debilitating epidemic
      keratoconjunctivitis. Local care and interventions to minimize transmission are
      the cornerstones of management. Infection is usually self-limiting. Warm soaks
      and artificial tear lubricants may relieve itching and burning. Patients should
      be instructed to avoid touching their eyes, wash hands often, use disposable
      towels, and avoid group activities for as long as an ocular discharge is present.
      Use of topical corticosteroids or antibacterial preparations can lead to
      complications, and injudicious use of topical corticosteroids may mask serious
      conditions that require other interventions.

PMID- 9158615
TI  - Attention-deficit hyperactivity disorder. Pharmacotherapy and beyond.
AB  - Management of ADHD is a challenge that requires time, commitment, and great
      sensitivity on the part of the physician. Use of stimulant medications is often
      successful at improving symptoms, but it has become the knee-jerk treatment
      response for many. Given the wide-ranging effects of ADHD on aspects of patients'
      lives and the availability of various treatment alternatives, a multimodal
      approach is considered optimal. As more studies evaluate nonpharmacologic
      approaches such as behavior therapy, parent education, and neurofeedback and more
      physicians implement multimodal treatment, outcomes for patients with ADHD are
      expected to be even more positive.

PMID- 9158616
TI  - Psychiatric illness in female physicians. Are high rates of depression an
      occupational hazard?
AB  - More than half of female physicians may experience a psychiatric illness during
      their lifetime. Depression is by far the most common such disorder, and the
      suicide rate is alarmingly high. However, female physicians appear to be at lower
      risk for substance abuse than male physicians. The medical profession could
      benefit from increased awareness of depression among female physicians and
      removal of barriers to treatment, such as stigma and discrimination against those
      with psychiatric illness.

PMID- 9158617
TI  - The hypercoagulable state. Who, how, and when to test and treat.
AB  - Patients with a family history of thrombosis, early-onset or recurring
      thrombosis, thrombosis at unusual sites, or warfarin-induced skin necrosis should
      be investigated for a possible underlying inherited hypercoagulable disorder.
      These include AT-III deficiency, protein C and S deficiencies, and APC
      resistance. Many patients should also be evaluated for the antiphospholipid
      syndrome, an acquired disorder. Functional assays are more useful than
      immunologic assays for diagnosing AT-III deficiency, protein C and S
      deficiencies, and APC resistance. A molecular probe is now available for the
      abnormal factor V most often responsible for APC resistance. Testing for the
      antiphospholipid syndrome involves assays for the lupus anticoagulant and
      anticardiolipin antibodies. AT-III and protein C concentrates are now available
      for short-term therapy. Long-term prophylactic administration of warfarin may
      have to be considered for some symptomatic patients with proven abnormalities,
      especially after more than one thrombotic event. While the management of
      asymptomatic persons remains controversial, the use of prophylactic
      anticoagulation should be anticipated for trauma, surgery, pregnancy, or other
      high-risk situations.

PMID- 9158618
TI  - Sex, science, and society. A look at sexually transmitted diseases.

PMID- 9158619
TI  - Tracking the itch. When to suspect migrating larvae.

PMID- 9158620
TI  - Complication rates for carotid endarterectomy. A call to action.

PMID- 9158621
TI  - Regional performance of carotid endarterectomy. Appropriateness, outcomes, and
      risk factors for complications.
AB  - BACKGROUND AND PURPOSE: Guided by the findings of randomized controlled trials
      evaluating carotid endarterectomy (CEA), we examined the appropriateness of CEAs
      performed in our city and determined the incidences and risk factors for
      postoperative stroke, death, and cardiac complications. METHODS: Using health
      records, we retrospectively reviewed 291 consecutive CEAs performed in our region
      over 18 months. Based on randomized controlled trial results and standardized
      remeasurements of angiographic carotid stenoses, indications for CEA were
      considered appropriate for symptomatic carotid stenoses > or = 70%, uncertain for
      < 70% symptomatic or > or = 60% asymptomatic stenoses, or inappropriate for < 60%
      asymptomatic stenoses and for patients with preoperative neurological or medical
      instability. RESULTS: We found that 41% of patients (118/291) were asymptomatic.
      Surgical indications were appropriate in 33% of cases (92/281), uncertain in 49%
      (138/281), and inappropriate in 18% (51/281). Stroke or death occurred within 30
      days postoperatively in 5.2% (9/174) of symptomatic patients and 5.1% (6/117) of
      asymptomatic patients. At least one cardiac complication (angina, congestive
      heart failure, dysrhythmia, or myocardial infarction) developed in 8.9% (26/291).
      Independent preoperative risk factors for stroke or death were histories of
      angina or congestive heart failure and lack of antiplatelet medication; for
      cardiac complications, risk factors were age > 75 years and a history of
      congestive heart failure. CONCLUSIONS: Almost 1 in 5 patients underwent CEA
      inappropriately, which was most commonly due to apparent over-estimation of
      stenosis severity, and half had uncertain indications. Our high complication rate
      possibly negated any overall surgical benefit in the large group of asymptomatic
      patients.

PMID- 9158622
TI  - Bilateral increase in CO2 reactivity after unilateral carotid endarterectomy.
AB  - BACKGROUND AND PURPOSE: A low or absent CO2 reactivity is considered indicative
      of a compromised hemodynamic compensatory capacity in patients with internal
      carotid artery (ICA) stenosis or occlusion. The aim of the present study was to
      investigate whether patients with preoperatively decreased or absent CO2
      reactivity show an improvement of CO2 reactivity 3 months after carotid
      endarterectomy (CEA) and whether the preoperative CO2 reactivity is correlated
      with clinical classification and hemodynamic factors. METHODS: A group of 65
      patients with > 70% ICA stenosis was studied. CO2 reactivity was measured by
      bilateral transcranial Doppler sonography before and 3 months after CEA. RESULTS:
      The preoperative CO2 reactivity was not significantly different in subgroups
      formed according to the presenting clinical symptoms. Patients with severe ICA
      stenosis with contralateral ICA occlusion had mean low preoperative CO2
      reactivity on both sides. Furthermore, patients with reversed flow in the
      ophthalmic artery had low mean preoperative CO2 reactivity on the same side. The
      CO2 reactivity was not significantly different in the subgroups of patients with
      signs of collateral blood flow through the anterior or posterior communicating
      artery. In particular, patients with low preoperative CO2 reactivity
      (approximately < 30%) showed an evident increase after the operation. Such an
      inverse correlation was found bilaterally, although it was more pronounced on the
      CEA side. CONCLUSIONS: CEA can increase CO2 reactivity in both hemispheres. This
      effect is most pronounced in patients with low (< 30%) preoperative CO2
      reactivity. If this group represents patients who would be at risk from low-flow
      stroke, then testing of CO2 reactivity might help select a subset of patients
      with an especially high probability of benefit from CEA.

PMID- 9158623
TI  - Internal and external carotid contributions to near-infrared spectroscopy during
      carotid endarterectomy.
AB  - BACKGROUND AND PURPOSE: The internal carotid (ICA) and external carotid (ECA)
      contributions to changing concentrations of oxyhemoglobin (Hbo2) and
      deoxyhemoglobin (Hb) during carotid endarterectomy were assessed with the use of
      near-infrared spectroscopy (NIRS). METHODS: NIRS optodes were placed on the
      forehead with an interoptode distance of 6 cm, and laser-Doppler flowmetry (LDF)
      was used to monitor the change in skin blood flow between the optodes. Hb, Hbo2,
      LDF, arterial blood pressure, and middle cerebral artery flow velocity were
      recorded continuously. The ECA was clamped 2 minutes before the ICA was clamped.
      Suitable multimodal recordings were achieved in 44 patients. RESULTS: When the
      ECA was clamped, 76% of patients showed a fall in Hbo2 and 65% an increase in Hb.
      When corrected for changes in arterial blood pressure, an accompanying fall in
      cutaneous LDF predicted the fall in Hbo2 with high sensitivity (100%) and
      specificity (100%). Among those with no NIRS changes during ECA clamping, 56% had
      severe ECA stenosis or occlusion; none of these showed an accompanying fall in
      LDF. In contrast, when the ICA was clamped, substantial additional changes in
      NIRS occurred in 55% of cases, all of which were associated with a fall in flow
      velocity, but none with a change in LDF. Patients with a constant flow velocity
      after ICA clamping also showed no change in NIRS. CONCLUSIONS: Both the ECA and
      ICA vascular territories contribute to NIRS changes during carotid
      endarterectomy. The external carotid contribution to NIRS can be monitored with
      cutaneous LDF.

PMID- 9158624
TI  - Stroke patients' knowledge of stroke. Influence on time to presentation.
AB  - BACKGROUND AND PURPOSE: New treatments for acute stroke will likely have to be
      given soon after stroke onset. Little is known about stroke patients' general
      knowledge about stroke, their interpretation of stroke symptoms, and how these
      factors influence the timing of their decision to seek medical attention.
      METHODS: We interviewed consecutive stroke patients within 72 hours of stroke
      onset to define factors influencing time of arrival to the emergency department.
      Data recorded included demographic information, method of transportation, type of
      stroke symptoms, the patient's interpretation of the symptoms, previous stroke,
      and knowledge of stroke warning signs. Stroke severity was measured with the
      Barthel Index. Early arrival was defined as within 3 hours of awareness of
      symptoms. RESULTS: Sixty-seven patients were interviewed; 96% had an ischemic
      stroke and 4% a cerebral hemorrhage. Although 38% of patients professed to know
      the warning signs of stroke, only 25% correctly interpreted their symptoms.
      Patients with prior stroke were more likely to correctly interpret their symptoms
      (45% versus 16%; P = .03) but were not more likely to present early (19% versus
      39%; P = .35). Eighty-six percent of patients presenting more than 3 hours after
      stroke onset thought that their symptoms were not serious. The 24% (n = 16) of
      early arrivals were more likely to arrive by ambulance (81% versus 38%; P = .003)
      and had more severe stroke (Barthel Index score of 49 versus 72; P = .01) than
      late arrivals. Arrival by ambulance was independently associated with early
      arrival (odds ratio, 5.55; 95% confidence interval, 1.37 to 22.6). CONCLUSIONS:
      Approximately one quarter of stroke patients correctly interpret their symptoms
      as representing a stroke. This knowledge is not associated with early
      presentation to the emergency department. Ambulance transport is independently
      associated with early arrival at the emergency department. Even when patients
      know that they are having a stroke, most present late because they perceive their
      symptoms as "not serious." Widespread public education of stroke-prone
      individuals may increase the proportion of patients eligible for new acute stroke
      treatments.

PMID- 9158625
TI  - Knowledge of risk among patients at increased risk for stroke.
AB  - BACKGROUND AND PURPOSE: Patients who recognize their increased risk for stroke
      are more likely to engage in (and comply with) stroke prevention practices than
      those who do not. We describe perceived risk of stroke among a nationally diverse
      sample of patients at increased risk for stroke and determine whether patients'
      knowledge of their stroke risk varied according to patients' demographic and
      clinical characteristics. METHODS: Respondents were recruited from the Academic
      Medical Center Consortium (n = 621, five academic medical centers, inpatients of
      varying age); the Cardiovascular Health Study (n = 321, population-based sample
      of persons aged 65+ years); and United HealthCare (n = 319, five health plans,
      inpatients and outpatients typically younger than 65 years). The primary outcome
      was awareness of being at risk for stroke. RESULTS: Only 41% of respondents were
      aware of their increased risk for stroke (including less than one half of
      patients with previous minor stroke). Approximately 74% of patients who recalled
      being told of their increased stroke risk by a physician acknowledged this risk
      in comparison with 28% of patients who did not recall being informed by a
      physician. Younger patients, depressed patients, those in poor current health,
      and those with a history of TIA were most likely to be aware of their stroke
      risk. CONCLUSIONS: Over one half of patients at increased risk of stroke are
      unaware of their risk. Healthcare providers play a crucial role in communicating
      information about risk, and successful communication encourages adoption of
      stroke prevention practices. Educational messages should be targeted toward
      patients least likely to be aware of their risk.

PMID- 9158626
TI  - Socioeconomic level, sedentary lifestyle, and wine consumption as possible
      explanations for geographic distribution of cerebrovascular disease mortality in
      Spain.
AB  - BACKGROUND AND PURPOSE: The geographic distribution of cerebrovascular disease
      (CVD) mortality in Spain spans a wide range, from provinces where mortality is
      low (70/100,000) and close to that of the United States and other Anglo-Saxon
      countries, to others where mortality is high (180/100,000) and more akin to that
      of Portugal and the Mediterranean and central European countries. This report
      seeks to identify the socioeconomic and lifestyle factors that most contribute to
      the geographic pattern of CVD mortality in Spain. METHODS: We performed a study
      using data collected at a provincial level. Mortality data were taken from
      official vital statistics, and data on risk factors were obtained from surveys of
      representative large Spanish population samples. Correlation and multiple linear
      regression analyses were performed on standardized CVD mortality ratios and
      potential determinants of mortality for the period 1989 to 1993. RESULTS: CVD
      mortality, unemployment and illiteracy rates, blond cigarette smoking, and
      sedentary lifestyle proved substantially higher in the south and east
      (Mediterranean coast) of Spain. Saturated fatty acid intake and wine consumption
      were both lower in these regions, however. Illiteracy, wine consumption,
      sedentary lifestyle, high blood pressure, blond cigarette smoking, prevalence of
      diabetes, and body mass index > or = 30 explained 59% of the variation in CVD
      mortality. Only illiteracy, sedentary lifestyle, and wine consumption registered
      a statistically significant relationship (P < .05) with CVD mortality. Whereas
      lower consumption of wine showed a negative association with CVD mortality,
      higher consumption revealed a positive association. CONCLUSIONS: Socioeconomic
      level, as measured by illiteracy, sedentary lifestyle, and wine consumption, may
      partly explain the higher CVD mortality registered for regions situated in the
      south and east of Spain.

PMID- 9158627
TI  - Race-ethnicity and determinants of carotid atherosclerosis in a multiethnic
      population. The Northern Manhattan Stroke Study.
AB  - BACKGROUND AND PURPOSE: Risk factors for carotid atherosclerosis have been
      studied in white populations but infrequently in multiethnic cohorts. The aim of
      this study was to determine the importance of race-ethnicity and other factors
      associated with carotid atherosclerosis in a mixed population of Hispanics,
      blacks, and whites. METHODS: As part of the Northern Manhattan Stroke Study, 526
      stroke-free community residents (aged > or = 40 years; 41% men, 59% women; 46%
      Hispanic, 31% black, 23% white) were recruited through random-digit dialing and
      had vascular risk factor evaluations. Maximum internal carotid artery plaque
      thickness (MICPT) was measured with B-mode ultrasound. The frequency distribution
      of MICPT was examined in the three race-ethnic groups, and multivariate
      regression was performed to identify factors that were independently associated
      with MICPT. RESULTS: Mean MICPT in the entire sample was 1.5 +/- 1.4 mm,
      increased directly with age, and was greater in whites and blacks than Hispanics.
      Other independent determinants of MICPT included smoking, glucose, LDL
      cholesterol, and hypertension. After we controlled for these covariates, Hispanic
      (versus non-Hispanic) race-ethnicity was still an independent determinant of less
      carotid plaque. There was a significant interaction between race-ethnicity and
      LDL cholesterol, with a greater effect of increasing LDL cholesterol among
      Hispanics. CONCLUSIONS: Atherosclerotic risk factors were predictive of MICPT in
      this mixed-ethnic cohort. Hispanics had significantly less carotid plaque after
      adjustment for other known risk factors, but they also had a greater impact of
      increasing LDL cholesterol.

PMID- 9158628
TI  - Evaluation of social status as a contributing factor to the stroke belt region of
      the United States.
AB  - BACKGROUND AND PURPOSE: The southeastern United States has stroke mortality rates
      above the national average. The causes for this excess mortality are unknown;
      however, lower socioeconomic status (SES) is a risk factor for stroke, and the
      lower SES in the Southeast is a potential cause. In this report we assess the
      proportion of the excess stroke mortality attributable to SES. METHODS: The more
      than 400,000 participants in the National Longitudinal Mortality Study were
      categorized into three regions: the coastal plain region of North Carolina, South
      Carolina, and Georgia ("stroke buckle"); the remainder of these states plus five
      other southern states ("stroke belt"); and the remainder of the United States.
      The stroke mortality rates were calculated with and without adjustment for SES,
      and the proportion of the excess mortality attributable to SES was estimated.
      RESULTS: In persons between the ages of 35 and 54 years, stroke mortality in the
      stroke buckle is estimated to be more than twice that of the rest of the nation
      and 1.7 times greater for ages 55 to 74 years. For persons in the stroke belt,
      the stroke mortality was 1.3 times greater than that in the rest of the nation
      for the ages of 35 to 54 and 55 to 74 years. Less than 16% of this excess stroke
      morality was attributable to SES. CONCLUSIONS: SES does not appear to be a major
      contributor to the excess mortality in the southeastern United States. Of
      additional concern is the stroke buckle region, which was shown to have stroke
      mortality rates substantially greater than those in the traditionally recognized
      stroke belt.

PMID- 9158629
TI  - Frequency and severity of asymptomatic coronary disease in patients with
      different causes of stroke.
AB  - BACKGROUND AND PURPOSE: We sought (1) to compare the frequency and severity of
      asymptomatic coronary artery disease (CAD) in patients with different causes of
      brain ischemia and (2) to determine profiles of patients with brain ischemia who
      are at highest risk of asymptomatic CAD. METHODS: Sixty-nine patients with
      transient ischemic attack or stroke and without overt CAD underwent a cardiac
      stress test and a diagnostic evaluation to determine the cause of brain ischemia.
      The frequency of abnormal cardiac stress tests was compared in patients with
      large-artery cerebrovascular disease versus other causes of brain ischemia (90%
      of whom had penetrating artery disease or cryptogenic stroke). Additionally, the
      frequencies of vascular risk factors, resting electrocardiographic abnormalities,
      and cause of stroke (large-artery disease versus other causes) were compared in
      patients with abnormal stress tests versus patients with normal stress tests.
      RESULTS: The frequency of abnormal stress tests was 50% (15 of 30) in patients
      with large-artery cerebrovascular disease versus 23% (9 of 39) in patients with
      other causes of brain ischemia (P = .04). Moreover, 60% of abnormal stress tests
      (9 of 15) in patients with large-artery cerebrovascular disease suggested severe
      underlying CAD that was confirmed in 7 of 7 patients who underwent coronary
      angiography. On the other hand, less than 25% of abnormal stress tests (2 of 9)
      in patients with other causes of brain ischemia suggested severe underlying CAD.
      Features that were more common in patients with abnormal stress tests were
      smoking (P = .006), large-artery cerebrovascular disease (P = .02), veteran
      status (P = .02), and left ventricular hypertrophy (P = .07). CONCLUSIONS:
      Patients with penetrating artery disease or cryptogenic stroke have a
      significantly lower frequency of asymptomatic CAD than patients with large-artery
      cerebrovascular disease. Large-artery cerebrovascular disease, smoking, veteran
      status, and possibly left ventricular hypertrophy may be useful features for
      identifying patients with transient ischemic attack or stroke who are at highest
      risk of harboring asymptomatic CAD.

PMID- 9158630
TI  - Stroke, statins, and cholesterol. A meta-analysis of randomized, placebo
      controlled, double-blind trials with HMG-CoA reductase inhibitors.
AB  - BACKGROUND AND PURPOSE: To estimate the effect of 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitors ("statins") on stroke ris, we combined
      the data of the randomized, placebo-controlled, double-blind trials with HMG-CoA
      reductase inhibitors published so far. METHODS: The studies were identified using
      the Medline CD+ and Current Contents databases from January 1980 through May
      1996, inclusive. All studies were evaluated on the use of a placebo control,
      monotherapy, and double blindness. When the type of stroke or the occurrence of
      clinical events or adverse effects were incompletely or not reported, the
      investigators were contacted personally. For each trial, the number of strokes in
      the treatment arm was compared with the number of strokes expected on all
      observations under the assumption that drug treatment had no effect. RESULTS: A
      total of 462 strokes among 20438 participants in 13 trials could be analyzed. A
      total of 181 strokes were observed in patients randomized to treatment with an
      HMG-CoA reductase inhibitor and 261 strokes in patients randomized to placebo. A
      lower than expected number of strokes was observed in the treatment groups of all
      but one trial (P = .001). Treatment with an HMG-CoA reductase inhibitor led to an
      overall risk reduction of 31% (odds ratio, 0.69; 95% confidence interval, 0.57 to
      0.83). CONCLUSIONS: The combined data suggest that treatment with HMG-CoA
      reductase inhibitors prevents stroke in middle-aged persons. Because stroke is
      especially common in older age, these data reinforce the need for clinical trials
      to evaluate the effect of HMG-CoA reductase inhibitors in preventing stroke in
      the elderly.

PMID- 9158631
TI  - Apolipoprotein E polymorphism and silent microangiopathy-related cerebral damage.
      Results of the Austrian Stroke Prevention Study.
AB  - BACKGROUND AND PURPOSE: Microangiopathy-related cerebral damage (MARCD) includes
      white matter abnormalities and lacunar infarctions and represents a common MRI
      observation in subjects above 50 years of age. The risk factors of such brain
      abnormalities are not fully determined. The goal of this study was to determine
      whether the genetic heterogeneity of apolipoprotein E (apoE) contributes to the
      occurrence of MARCD. METHODS: Brain MRI (1.5 T) was performed in 280 individuals
      (ages 50 to 75 years) without neuropsychiatric disease randomly selected from the
      official register of residents of the city of Graz, Austria. All study
      participants underwent apoE genotyping, carotid Doppler sonography,
      electrocardiography, echocardiography, and a complete blood chemistry panel.
      MARCD was defined as evidence of early confluent and confluent white matter
      hyperintensities or lacunes. Carotid atherosclerosis was graded on a five-point
      scale ranging from not present (0) to complete occlusion (5). RESULTS: MARCD
      occurred in 61 individuals (21%). The distribution of apoE genotypes differed
      significantly between subjects with and without MARCD (P = .036). Subjects with
      such findings more commonly had the epsilon 2/epsilon 3 genotype (24.6% versus
      10%) at similar frequencies of genotypes containing the epsilon 4 allele. The
      epsilon 2/epsilon 3 genotype was associated with lower levels of total
      cholesterol (P = .0009), LDL cholesterol (P = .00001), and apolipoprotein B (P =
      .00001). Also, there was a nonsignificant trend toward less cardiac disease.
      Other major vascular risk factors and carotid abnormalities were similar among
      the various genotypes. Multiple logistic regression analysis created a model of
      significant MARCD predictors, including age (odds ratio [OR], 1.1 per year),
      hypertension (OR, 3.4), and the apoE epsilon 2/epsilon 3 genotype (OR, 3.0).
      CONCLUSIONS: These data suggest an association between the apoE epsilon 2/epsilon
      3 genotype and MARCD despite favorable effects on the lipid profile and cardiac
      disease.

PMID- 9158632
TI  - Hemorrhagic transformation in acute ischemic stroke. Potential contributing
      factors in the European Cooperative Acute Stroke Study.
AB  - BACKGROUND AND PURPOSE: Recent studies suggest that thrombolytic therapy may be
      of benefit to patients with acute ischemic stroke. However, the treatment also
      carries a significant risk of hemorrhagic transformation (HT). The purpose of
      this study was to select potential contributors to HT. METHODS: We provide an
      explanatory analysis of the European Cooperative Acute Stroke Study (ECASS) data.
      ECASS was a multicenter, placebo-controlled, randomized trial of recombinant
      tissue plasminogen activator in ischemic stroke, within 6 hours of symptom onset,
      which enrolled 620 patients. HTs were classified into either hemorrhagic
      infarction or parenchymal hemorrhage according to their CT scan appearance. We
      used logistic regression analysis to select potential contributing factors to
      each type of HT. RESULTS: The severity of initial clinical deficit (odds ratio
      [OR], 2.5; 95% confidence interval [CI], 1.6 to 4.0) and the presence of early
      ischemic changes on CT scan (OR, 3.5; 95% CI, 2.3 to 5.3) were associated with
      increased risk of hemorrhagic infarction. Increasing age (in decades; OR, 1.3;
      95% CI, 1.0 to 1.7) and treatment with recombinant tissue plasminogen activator
      (OR, 3.6; 95% CI, 2.1 to 6.1) were related to the risk of parenchymal hemorrhage.
      CONCLUSIONS: Since all potential contributing factors are readily discernible
      upon hospital admission, they should be used to improve selection of patients
      into future studies.

PMID- 9158633
TI  - Intracerebral hemorrhage in blacks. Risk factors, subtypes, and outcome.
AB  - BACKGROUND AND PURPOSE: Blacks are at a higher risk for intracerebral hemorrhage
      (ICH) than whites; however, few data are available regarding the demographic and
      clinical characteristics of ICH among blacks. METHODS: We determined the
      frequency of risk factors, etiologic subtypes, and outcome among consecutive
      black patients admitted with nontraumatic ICH to a university-affiliated public
      hospital. RESULTS: The most common risk factors in the 403 black patients with
      ICH were preexisting hypertension (77%), alcohol use (40%), and smoking (30%).
      Among the 91 nonhypertensive patients, 21 (23%) were diagnosed with hypertension
      after onset. Compared with women, men had a younger age of onset (54 versus 60
      years; P < .001) and higher frequency of alcohol use (54% versus 22%; P < .001)
      and smoking (39% versus 17%; P < .001). ICH secondary to hypertension (n = 311)
      and of undetermined etiology (n = 73) were the most common subtypes in blacks.
      Patients aged 65 years and older (compared with those aged 15 to 44 years; P =
      .001) and women (compared with men; P = .02) were more likely to be dependent at
      discharge. CONCLUSIONS: Primary preventive strategies are required to reduce the
      high frequency of modifiable risk factors predisposing to ICH in blacks.

PMID- 9158634
TI  - Neurological signs and frontal white matter lesions in vascular parkinsonism. A
      clinicopathologic study.
AB  - BACKGROUND AND PURPOSE: The clinical characteristics and the pathological lesions
      of so-called vascular parkinsonism (VP) are still debatable. The purpose of this
      study was to define the core signs and symptoms and assess the cerebrovascular
      lesions in pathologically confirmed VP. METHODS: In the present study, VP was
      defined as the presence of parkinsonism and pathological evidence of
      cerebrovascular lesions but no depigmentation or Lewy bodies at the substantia
      nigra. We compared the clinical signs and symptoms of 24 VP patients with those
      of 30 age-matched patients with pathologically confirmed Parkinson's disease. We
      compared the brain pathology in VP patients with that in 22 age-matched patients
      with Binswanger's disease (BD) who had no parkinsonism according to clinical
      records. RESULTS: VP was characterized clinically by a short-stepped or frozen
      gait, lead-pipe rigidity, absence of resting tremor, and negative response to
      levodopa. Half or more of VP patients demonstrated pyramidal tract signs and
      pseudobulbar palsies. There was no significant difference in the extent of
      vascular lesions at the basal ganglia between patients with VP and with BD
      without parkinsonism. The extent of frontal white matter pallor tended to be less
      broad in VP than in BD without parkinsonism. In VP patients, the number of
      oligodendrocytes in the frontal white matter was significantly less than that in
      age-matched normal control subjects and significantly more than in those with BD.
      CONCLUSIONS: The core signs and symptoms of autopsy-proved VP differ from those
      of typical Parkinson's disease, and most VP patients had diffuse cerebral white
      matter lesions as well as basal ganglia lesions. VP might be related to frontal
      white matter lesions.

PMID- 9158635
TI  - Long-term cognitive impairment associated with caudate stroke.
AB  - BACKGROUND AND PURPOSE: Neuropsychiatric findings were examined in 91 patients
      with acute focal subcortical lesions to determine whether cognitive outcome would
      differ depending on whether the head of the caudate or other subcortical
      structures were injured. METHODS: Patients were evaluated using the Mini-Mental
      State Examination (MMSE), Hamilton Rating Scale for Depression, and modified
      Present State Examination. Patients were reexamined at short-term (3 to 6 months)
      or long-term (1 to 2 years) follow-up. RESULTS: There were no significant
      intergroup differences in the MMSE scores at the initial evaluation or at short
      term follow-up. At long-term follow-up, however, patients with either right or
      left caudate lesions had significantly lower MMSE scores than patients with other
      subcortical lesions. CONCLUSIONS: A significant number of patients with caudate
      infarction deteriorate in their intellectual function between 1 and 2 years after
      stroke. This phenomenon could be mediated through disruption of cortical
      projections to the caudate.

PMID- 9158636
TI  - Sensitivity and specificity of 99mTc-HMPAO SPECT cerebral perfusion measurements
      during the first 48 hours for the localization of cerebral infarction.
AB  - BACKGROUND AND PURPOSE: There is no routinely used method for imaging the
      location of the extent and severity of cerebral tissue perfusion changes during
      the first hours of ischemic stroke, the period during which therapeutic
      intervention is most likely to be successful. Cerebral perfusion measurements
      with single-photon emission CT (SPECT) may potentially provide this information
      rapidly and noninvasively. In this study, the sensitivity and specificity of
      99mTc-hexamethylpropyleneamine oxime (HMPAO) SPECT cerebral perfusion
      measurements during the first 48 hours of cerebral ischemia for the localization
      of cerebral infarction were determined. METHODS: One hundred and four patients
      with acute ischemic stroke underwent 99mTc-HMPAO SPECT and CT scanning during the
      first 48 hours. In each patient, the location of the SPECT perfusion abnormality
      was compared with the location of infarction on a second brain CT acquired at a
      mean of 8 days after stroke. RESULTS: During the first 48 hours of ischemic
      stroke, the sensitivity of 99mTc-HMPAO SPECT in locating the site of infarction
      was 79% (110/139), and the specificity was 95% (362/381). SPECT was more
      sensitive in the localization of the vascular territory of cortical infarction
      (sensitivity, 93%) than pure subcortical infarcts (sensitivity, 47%). During the
      first 48 hours, SPECT was significantly more sensitive than brain CT (sensitivity
      of brain CT during the first 48 hours, 35%; P < .001, Mann-Whitney U test).
      CONCLUSIONS: HMPAO SPECT measurement provides a widely available and practical
      technique of locating cerebral ischemia acutely and demonstrates high sensitivity
      and specificity within the first 48 hours for the localization of the vascular
      territory of cerebral infarction. It is most sensitive for cortical ischemia but
      is limited by its resolution in the subcortex, particularly of white matter
      perfusion changes.

PMID- 9158637
TI  - Implementation of a stroke code system in Mobile, Alabama. Diagnostic and
      therapeutic yield.
AB  - BACKGROUND AND PURPOSE: There is now therapy of proven benefit for acute ischemic
      stroke. Successful interventional therapy for stroke patients requires
      implementation of a system that facilitates rapid triage and diagnostic
      evaluation. METHODS: We initiated a 24-hour, 7-day-per-week stroke code system at
      the University of South Alabama Hospitals and prospectively collected data from
      the first 100 patients whose clinical presentations triggered this system.
      RESULTS: Seventy-eight patients (78%) had acute ischemic stroke. Of the remaining
      22, 9 had evidence of intracerebral hemorrhage. The most common nonstroke
      diagnosis was seizure (n = 5). Forty-eight of the 87 stroke patients (55%)
      presented within 6 hours of stroke onset (40/78 = 51% of the ischemic stroke
      patients), and 35 of the 87 (40%) presented within 3 hours of onset (28/78 = 36%
      of the ischemic stroke patients). Thirty-one (31% of the group overall; 40% of
      the ischemic stroke patients) were eligible for acute therapy. Twenty-five of
      these eligible patients were entered into a treatment study, 4 declined
      participation, and 2 were treated with open-label tissue plasminogen activator.
      CONCLUSIONS: Implementation of a stroke code system may result in a high yield of
      patients with acute stroke and relatively few "stroke mimickers." A significant
      proportion of all cases generated will be eligible for acute treatment under
      current experimental protocols or with tissue plasminogen activator, but the
      majority will not.

PMID- 9158638
TI  - Xenon contrast CT-CBF measurements in high-intensity foci on T2-weighted MR
      images in centrum semiovale of asymptomatic individuals.
AB  - BACKGROUND AND PURPOSE: White matter lesions (WMLs) on T2-weighted MR images
      occurring in the centrum semiovale of normal individuals are a subject of great
      clinical interest. We therefore investigated regional cerebral blood flow (rCBF)
      of the centrum semiovale among neurologically normal individuals. METHODS: One
      hundred thirty-five neurologically normal subjects were divided into four grades
      of WML on the basis of their MR images. rCBF values in the centrum semiovale were
      measured by xenon contrast CT methods. RESULTS: Advanced age and associated
      hypertension were significant risk factors for higher grade WMLs. Centrum
      semiovale rCBF values on the left side were 24.27 +/- 2.60 mL.100 g-1.min-1 in
      grade 0, 23.52 +/- 2.78 in grade I, 19.35 +/- 2.81 in grade II, 15.82 +/- 2.05 in
      grade III, and 11.31 +/- 2.56 in grade IV. Differences were significant between
      grades (P < .005 between grade 0 and grades II, III, and IV; between grade II and
      grades III and IV; and between grades III and IV). Patients with hypertension had
      lower rCBF values than those without in grades 0, I, II, and III, with
      significant difference in grade I (P < .005). Age-matched studies between
      patients 61 to 70 years old confirmed a significant difference between WML
      grades. CONCLUSIONS: WMLs in centrum semiovale are associated with greater age,
      hypertension, and reduced rCBF values.

PMID- 9158639
TI  - Low-velocity graded treadmill stress testing in hemiparetic stroke patients.
AB  - BACKGROUND AND PURPOSE: Coronary artery disease is prevalent in stroke patients
      and is an important factor affecting rehabilitation and health outcomes. However,
      the presence of neurological deficits in gait and balance has discouraged
      systematic application of exercise testing and prescription in the stroke
      population. We evaluated a novel graded treadmill stress test in paretic stroke
      patients and tested floor walking as a predictor of adequate neurological
      function to perform the treadmill test. METHODS: Patients (n = 31) with residual
      paretic gait deficits after ischemic stroke were evaluated with graded treadmill
      at gait velocities individualized to functional mobility observed during an
      initial zero-incline treadmill tolerance test. RESULTS: Most patients (30/31)
      tolerated testing, achieving mean heart rates of 129 +/- 14 beats per minute
      (mean +/- SD), representing 84 +/- 10% of maximal age-predicted heart rate.
      Evidence for asymptomatic myocardial ischemia was found in 29% of those without
      known coronary artery disease. Exercise termination was more often due to
      generalized fatigue than cardiopulmonary intolerance (23/31 versus 4/31; P <
      .0001) or hemiparetic leg fatigue (1/31; P < .0001). Floor walking across a wide
      range of velocities (0.25 to 2.5 mph) demonstrated a strong linear relation with
      treadmill velocities (n = 24; r = 80; P < .0001); all patients floor walking at >
      or = 0.5 mph had adequate neuromotor function to perform the exercise test.
      CONCLUSIONS: These findings suggest that graded treadmill exercise testing, with
      proper safety precautions, can be used to assess cardiopulmonary function in
      paretic stroke patients. A simple floor-walking test predicts adequate
      neurological function to perform the exercise test. Exercise capacity is most
      limited by generalized fatigue and not by the paretic limb, supporting a
      rationale for endurance training in this population.

PMID- 9158640
TI  - In vivo association between low wall shear stress and plaque in subjects with
      asymmetrical carotid atherosclerosis.
AB  - BACKGROUND AND PURPOSE: It is known that atherosclerosis does not involve both
      carotid arteries to the same extent. Pathological investigations have
      demonstrated that lesions develop in regions of low wall shear stress. The aims
      of the present study were to verify the degree of carotid atherosclerosis
      asymmetry in a population-based study and to evaluate whether wall shear stress
      is lower in carotids with atherosclerotic lesions than in carotids without
      lesions. METHODS: Participants in a cardiovascular disease prevention campaign (n
      = 1166) were screened for carotid atherosclerosis by echo-Doppler examination. Of
      these, 23 subjects who presented plaque in the common carotid or bulb of one side
      and no plaque in the contralateral carotid tree were enrolled for common carotid
      wall shear stress measurement. Shear stress was calculated according to the
      following formula: Shear Stress = Blood Viscosity x Blood Velocity/Internal
      Diameter. RESULTS: Of the 1166 subjects screened, 400 (34%) had plaque and/or
      stenosis in the carotids. Ninety subjects had lesions exclusively in the right
      carotid, 111 had lesions exclusively in the left, 70 had lesions in both carotids
      but with different degrees of severity, and only 129 had similar lesions in both
      carotids. In the 23 subjects in whom wall shear stress was measured, peak shear
      stress was 18.7 +/- 4.1 and 15.3 +/- 4.0 dynes.cm-2 (mean +/- SD) (P < .0001) in
      the side without and the side with plaque, respectively. Mean shear stress
      yielded similar results. CONCLUSIONS: The present results demonstrate that the
      atherosclerotic involvement of carotid arteries is usually asymmetrical and that
      wall shear stress is lower in the carotid arteries where plaques are present than
      in plaque-free arteries. These findings provide in vivo evidence for a strong
      association between shear stress and atherosclerotic lesions.

PMID- 9158641
TI  - Duration of diabetes and carotid wall thickness. The Insulin Resistance
      Atherosclerosis Study (IRAS).
AB  - BACKGROUND AND PURPOSE: Diabetes is a major risk factor for morbidity and
      mortality from cardiovascular disease. However, the role of the primary metabolic
      abnormality of diabetes (chronic hyperglycemia) in this disease process has not
      been fully elucidated. METHODS: A cross-sectional analysis was conducted among
      489 persons with non-insulin-dependent diabetes mellitus; 299 were established
      diabetics (diagnosed previously) and 190 were newly diagnosed at the time of the
      Insulin Resistance Atherosclerosis Study (IRAS) examination. These men and women,
      of three different ethnic groups, were participants in IRAS. Established diabetes
      (versus newly diagnosed diabetes) and mean fasting glucose level were used as
      measures of hyperglycemic burden. Intimal-medial wall thickness (IMT) of the
      internal (ICA) and common (CCA) carotid arteries were used as indices of
      atherosclerosis. RESULTS: The mean duration of disease among established
      diabetics was 7 years. The mean CCA IMT and ICA IMT were 872 and 946 microns,
      respectively. Established diabetes and mean fasting glucose level were positively
      associated with increased CCA IMT (P < .05) but not ICA IMT, even after
      adjustment for numerous cardiovascular disease risk factors. CCA IMT was
      increased by 70 microns in established diabetics (versus newly diagnosed
      diabetics) and by 26 microns per 1 SD of fasting glucose. Among established
      diabetics, however, duration of known diabetes (number of years) was not
      significantly related to IMT. CONCLUSIONS: Among diabetics in IRAS, established
      diabetes and fasting glucose level were each independently associated with CCA
      IMT, suggesting that chronic hyperglycemia or its associated metabolic
      abnormalities may lead to increased risk of atherosclerosis.

PMID- 9158642
TI  - Characteristics of transcranial Doppler signal enhancement using a phospholipid
      containing echocontrast agent.
AB  - BACKGROUND AND PURPOSE: Ultrasound attenuation caused by the skull is a major
      limitation of transcranial Doppler. Echocontrast agents (EAs) may solve this
      problem. The aim of the present study was to investigate the characteristics of a
      new echocontrast agent (BY963) containing air bubbles stabilized by
      phospholipids. METHODS: Nine healthy volunteers received three different doses
      (2.5, 5.0, and 10 mL) of BY963 at an injection rate of 0.25 mL/s. The Doppler
      signal amplitude obtained from the middle cerebral artery was recorded with a 2
      MHz pulsed-wave Doppler system. After complete decay of the signal enhancement,
      upward stroking of the veins of the upper arm was performed to evaluate the
      stability of the EA in the venous system. RESULTS: A dose-dependent increase of
      at least 30 dB in the Doppler signal amplitude lasted 19 to 47, 35 to 64, and 48
      to 126 heart cycles (68% range) after 2.5, 5.0, and 10 mL EA, respectively. In 6
      cases, there was a biphasic increase in EA enhancement. Upward stroking of the
      forearm, in general 12 to 18 minutes after administration, caused a Doppler
      signal enhancement of at least 30 dB in 6 cases. CONCLUSIONS: Each injection of
      BY963 caused a diagnostically relevant Doppler signal enhancement. A considerable
      amount of EA remained stable in the venous system for at least 12 minutes. The
      biphasic dose-response fits to models of dilution-indicator theory and indicates
      free recirculation, as well as a nonlinear washout curve.

PMID- 9158643
TI  - Application of interhemispheric index for transcranial Doppler sonography
      velocity measurements and evaluation of recording time.
AB  - BACKGROUND AND PURPOSE: To validate the reliability of transcranial Doppler
      sonography velocity measurements in clinical settings, assessment of the
      reproducibility of repeated bilateral simultaneous measurements and the optimal
      recording time is needed. Our hypothesis was that interhemispheric indices would
      prove more valid than the absolute velocity measurements usually applied. The
      potential interference between ultrasound beams in bilateral samplings also needs
      evaluation. METHODS: Thirty healthy volunteers were studied at rest within hours
      or with a 2-month interval between measurements. Absolute blood flow velocities
      and side-to-side indices between velocities obtained in the middle cerebral
      arteries were measured over a 30-second period by two independent examiners. The
      correlation coefficient (r) and the coefficients of variation of the difference
      between either absolute velocities (CV) or indices (CVi) were calculated. The
      beat-to-beat variation of the diastolic, systolic, and mean velocities was also
      recorded. For evaluation of ultrasound beam interference, measurements were
      performed with and without one probe unplugged. RESULTS: In the interobserver
      study in which measurements were repeated within hours, r = .92, CV = 8.8%, and
      CVi = 4.1%. In the intraobserver study in which measurements were repeated with a
      2-month interval, r = .8, CV = 13.0%, and CVi = 7.3%. A recording time of 30
      seconds reduced CVi to 2.6%, whereas for absolute velocities 5-second recordings
      produced an acceptable variation. There was no significant interference between
      bilaterally placed probes. CONCLUSIONS: The introduction of interhemispheric
      indices improve interobserver and intraobserver reproducibility by approximately
      50%. We recommend use of the index in clinical settings in which unilateral
      velocity changes are expected. For measurement of an interhemispheric index, a
      recording time of 30 seconds is recommended, whereas 5-second measurement periods
      yield a sufficient estimate of absolute velocities.

PMID- 9158645
TI  - Cerebral infarcts related to isolated middle cerebral artery stenosis.
AB  - BACKGROUND AND PURPOSE: The clinical presentation of middle cerebral artery (MCA)
      stenosis, a rarely diagnosed condition, is not well known. The aim of this study
      was to analyze the stroke patterns of patients with isolated MCA stenosis.
      METHODS: Twenty-two patients with cerebral infarcts due to isolated MCA stenosis
      were analyzed with respect to their clinical syndrome, and cerebral lesions were
      assessed by neuroimaging. MCA stenosis was diagnosed by transcranial Doppler
      sonography (TCD) in 16, by TCD and digital subtraction angiography (DSA) in 4,
      and by DSA alone in 2 patients. RESULTS: Ten patients (45.5%) had lacunar
      syndromes, suggesting small-vessel disease, and 12 patients (55.5%) showed signs
      and symptoms of cortical dysfunction. Cerebral CT or MRI showed no lesion in 2
      patients, small deep infarcts in 10, large striatocapsular infarcts in 2,
      combined piomedullary and striatocapsular infarcts in 4, piomedullary branch
      infarcts in 3, and MCA trunk infarct in 1. CONCLUSIONS: The results suggest an
      association between MCA stenosis and (1) lacunar infarcts and (2) the occurrence
      of piomedullary MCA branch infarcts alone or in combination with subcortical
      infarcts. The clinical syndromes and the radiological findings correspond in most
      cases.

PMID- 9158644
TI  - Indobufen versus warfarin in the secondary prevention of major vascular events in
      nonrheumatic atrial fibrillation. SIFA (Studio Italiano Fibrillazione Atriale)
      Investigators.
AB  - BACKGROUND AND PURPOSE: The results of a large prospective randomized trial have
      shown the efficacy of oral anticoagulation in the secondary prevention of major
      vascular events in patients with nonrheumatic atrial fibrillation (NRAF); less
      well established is the role of antiplatelet agents. The present study compared
      the effects of indobufen, a reversible inhibitor of platelet cyclooxygenase, with
      those of warfarin in this setting. METHODS: A total of 916 patients with NRAF and
      a recent (< or = 15 days) cerebral ischemic episode were admitted to this
      multicenter, randomized study, during which they were treated with either
      indobufen (100 or 200 mg BID) or warfarin (to obtain an international normalized
      ratio of 2.0 to 3.5) for 12 months. The two groups (462 on indobufen and 454 on
      warfarin) were well balanced in terms of their main baseline characteristics. The
      primary outcome of the study was the combined incidence of nonfatal stroke
      (including intracerebral bleeding), pulmonary or systemic embolism, nonfatal
      myocardial infarction, and vascular death. RESULTS: At the end of follow-up, the
      incidence of primary outcome events was 10.6% in the indobufen group (95%
      confidence interval, 7.7% to 13.5%) and 9.0% in the warfarin group (95%
      confidence interval, 6.3% to 11.8%), with no statistically significant difference
      between treatments. The frequency of noncerebral major bleeding complications was
      low: only four cases (0.9%) of gastrointestinal bleeding were observed, all of
      them in the warfarin group. CONCLUSIONS: We conclude that, within the limitations
      of its design, this study may help the medical community in devising appropriate
      antithrombotic strategies for NRAF patients for whom oral anticoagulants are
      contraindicated or do not represent a feasible approach to treatment.

PMID- 9158646
TI  - Cerebrovascular changes in chronic hypertension. Protective effects of enalapril
      in rats.
AB  - BACKGROUND AND PURPOSE: Our recent study demonstrated that in chronic
      hypertension, hypertrophy of intracerebral arterioles was associated with an
      increase in the vascular extracellular matrix proteins: fibronectin, laminin, and
      collagen IV. An additional cerebral finding in chronic hypertension was
      hypertensive encephalopathy, in which breakdown of the blood-brain barrier (BBB)
      to serum proteins occurred in multifocal areas of the cortex and basal ganglia.
      This study was undertaken to determine which of these alterations were attenuated
      by antihypertensive therapy. METHODS: Two weeks after the surgery to produce
      chronic renal hypertension, half the hypertensive rats were treated orally with
      enalapril (30 mg/kg), an angiotensin-converting enzyme inhibitor, for 5 weeks.
      Rats were perfusion-fixed, and their brains were removed and processed for
      morphological studies. The effect of treatment on vascular hypertrophy was
      assessed by quantitative morphometry and on the vascular extracellular matrix
      proteins and BBB permeability alterations by immunohistochemistry. RESULTS: There
      was increased immunoreactivity for laminin, fibronectin, and collagen IV in pial
      and intracerebral arterioles of untreated hypertensive rats. Immunoreactivity was
      greatest in arterioles in areas with breakdown of the BBB to serum proteins.
      Enalapril treatment for 5 weeks resulted in a significant reduction of the mean
      systolic blood pressure, which was accompanied by attenuation of vascular
      hypertrophy and attenuation of changes in the vascular extracellular matrix
      proteins. In addition, there was reduction in the magnitude of BBB breakdown
      after treatment. CONCLUSIONS: Enalapril treatment had a protective effect and
      attenuated vascular hypertrophy and the increase in vascular extracellular matrix
      proteins observed in chronic hypertension. In addition, there was reduction in
      the magnitude of BBB breakdown.

PMID- 9158647
TI  - Genetic susceptibility to experimental cerebral aneurysm formation in the rat.
AB  - BACKGROUND AND PURPOSE: The susceptibility to experimental cerebral aneurysm
      formation in arteries of the circle of Willis was studied in four strains of rats
      presenting different susceptibilities to the spontaneous rupture of the internal
      elastic lamina in extracerebral arteries: Brown-Norway (BN) > Wistar > Long-Evans
      (LE) > LOU. METHODS: Rats (150 g body weight) of the four strains were subjected
      to hypertension and a change in local cerebral blood flow by ligation of one
      common carotid artery for about 7 months. Six-month-old BN and LE rats were
      subjected to carotid ligation only for 11 to 13.5 months and treated or not (from
      3 to 7 months of age) with an inhibitor of connective tissue fiber maturation,
      beta-aminopropionitrile (BAPN). RESULTS: Aneurysmal structures (AS) occurred
      mainly in the anterior cerebral/anterior communicating arterial complex and
      proximal part of the posterior artery. In hypertensive rats, the AS incidence was
      LE, 56%; Wistar, 33%; BN, 17%; and LOU, 11%. When normotensive and subjected to
      carotid ligation only, LE rats showed an even greater susceptibility to AS
      formation (86%) than BN (7%). BAPN treatment did not influence AS formation: LE
      (60%) versus BN (8%). CONCLUSIONS: These results suggest that genetic factors are
      involved in cerebral aneurysm formation in the rat. The susceptibility of the
      internal elastic lamina of extracerebral arteries to spontaneous rupture does not
      appear to be a determinant genetic trait in the propensity to develop aneurysms
      in arteries of the circle of Willis. The comparison of these different rat
      strains may be very useful for studying factors contributing to cerebral aneurysm
      pathogenesis.

PMID- 9158648
TI  - Chronic cerebral hypoperfusion inhibits calcium-induced long-term potentiation in
      rats.
AB  - BACKGROUND AND PURPOSE: Long-term potentiation (LTP) in the rat hippocampus
      induced by tetanic stimulation is impaired by chronic cerebral hypoperfusion. The
      effects of chronic cerebral hypoperfusion on other forms of LTP are unknown. Such
      data could help delineate the pathways of cellular alteration caused by chronic
      cerebral hypoperfusion. The in vitro phenomenon of calcium-induced LTP was thus
      examined in rat hippocampal CA1 cells that had undergone chronic hypoperfusion
      with a reduction in cerebral blood flow of between 25% and 50% maintained for 26
      weeks. METHODS: Ten Sprague-Dawley rats had a cervical arteriovenous fistula
      surgically constructed, and an additional 10 animals were used as age-matched
      controls. Hippocampal slices were prepared after 26 weeks of hypoperfusion, and
      in vitro extracellular field potential recordings were taken from the Schaffer
      collateral CA1 region. Properties of LTP induced through transient exposure to a
      hypercalcemic solution were analyzed. RESULTS: LTP was impaired in animals with
      an arteriovenous fistula (P < .05). Control animals demonstrated potentiation
      lasting for the entire 2 hours of recording, whereas fistula animals showed only
      transient potentiation (< 60 minutes) before returning to baseline values.
      CONCLUSIONS: Calcium-induced LTP is impaired by chronic cerebral hypoperfusion.
      This form of LTP is different from that induced by tetanic stimulation. It is the
      most sensitive test available for in vitro detection of the changes induced in
      neuronal function by chronic noninfarctional reductions in cerebral blood flow of
      25% to 50% and may indicate that the most basic cellular parameters involving
      calcium homeostasis and metabolism are being altered. The precise mechanisms
      remain to be elucidated, and several postulates are discussed.

PMID- 9158649
TI  - Short- and long-term changes in striatal neurons and astroglia after transient
      forebrain ischemia in rats.
AB  - BACKGROUND AND PURPOSE: The striatum is one of the regions most sensitive to
      transient forebrain ischemia. After 30-minute ischemia, areas of massive neuronal
      degeneration are clearly detectable a few hours after the insult and attain their
      maximal extension 24 hours after the insult. However, for most cellular and
      neurochemical parameters it is not known whether some recovery occurs at later
      times. We examined certain cell populations in the caudate putamen at different
      times after transient ischemia. METHODS: Adult male Sprague-Dawley rats were
      subjected to 30-minute forebrain ischemia (four-vessel occlusion model). Six
      experimental groups were considered: control animals and ischemic animals killed
      4 hours, 1 day, 7 days, 40 days, and 8 months after reperfusion. Three striatal
      cell populations were examined by means of immunocytochemistry coupled to
      computer-assisted image analysis: vulnerable medium spiny neurons, resistant
      aspiny neurons, and reactive astrocytes, labeled for their content of dopamine-
      and cAMP-regulated phosphoprotein mr32 (DARPP-32), somatostatin and neuropeptide
      Y, and glial fibrillary acidic protein, respectively. RESULTS: (1) The area
      containing DARPP-32 immunoreactive neurons was markedly decreased (15% to 20% of
      control caudate putamen area) at 1 day after reperfusion and partially recovered
      at the following times (40% to 50% at 7 days and 50% to 60% at 40 days and 8
      months after reperfusion). (2) The appearance of reactive astrocytes was
      precocious (4 hours to 1 day after ischemia) in the medial caudate putamen, the
      region in which DARPP-32 recovered within 40 days after ischemia, and late (7 to
      40 days after ischemia) in the lateral caudate putamen, where no DARPP-32
      recovery was detected. (3) Neuropeptide Y/somatostatin-containing neurons
      resisted the ischemic insult and could be detected in areas devoid of DARPP-32
      immunoreactive neurons as long as 8 months after reperfusion. CONCLUSIONS: The
      present results show a marked recovery of DARPP-32-positive neurons within 40
      days after 30-minute forebrain ischemia in the medial, but not the lateral,
      caudate putamen. Medial caudate putamen also contains a high density of reactive
      astrocytes on the first day after ischemia, suggesting that astrocytic support
      has an important role in the spontaneous recovery of ischemic neurons.

PMID- 9158650
TI  - Synergistic effects of citicoline and MK-801 in temporary experimental focal
      ischemia in rats.
AB  - BACKGROUND AND PURPOSE: Citicoline, a naturally occurring precursor of
      phosphatidylcholine, is neuroprotective and is currently being assessed in
      clinical trials. To evaluate potential synergistic neuroprotective effects of
      prolonged citicoline treatment and early N-methyl-D-aspartate (NMDA) antagonist
      therapy, suboptimal treatment regimens of citicoline and MK-801 were tested alone
      and in combination in a rat model of temporary focal ischemia. METHODS: Four
      groups of Sprague-Dawley rats (n = 12 per group) underwent 90 minutes of
      temporary middle cerebral artery occlusion (MCAO) with the suture model. Animals
      were randomly and blindly assigned to one of four treatment groups: (1) saline,
      vehicle; (2) MK-801, 0.5 mg/kg IV bolus at 60 minutes after MCAO followed by
      saline 1 mL/kg IP daily for 7 days; (3) saline IV at 60 minutes after MCAO
      followed by citicoline 250 mg/kg IP daily for 7 days; or (4) both MK-801 and
      citicoline (daily for 7 days) active treatment. Triphenyltetrazolium chloride
      staining was used to assess postmortem infarct volume. Neurological scores were
      determined daily. RESULTS: Premature mortality between days 2 and 4 was 33.3% in
      group 1, 41.7% in groups 2 and 3, and 25.0% in group 4. Mean corrected infarct
      volume was significantly reduced in group 4 compared with the others (175.2 +/-
      89.3 mm3 in group 1, 179.1 +/- 78.5 mm3 in group 2, 163.9 +/- 73.7 mm3 in group
      3, and 84.7 +/- 56.8 mm3 in group 4 [P < .02, ANOVA and P < .05, Scheffe's test
      for group 1 versus group 4]). Mean infarct volume in animals dying prematurely
      was significantly (P < .05, Student's t test) larger in group 1 than those
      surviving for 7 days (247.2 +/- 89.5 versus 139.2 +/- 68.2 mm3), but there was no
      significant difference in infarct volume in groups 2, 3, and 4 between animals
      dying prematurely and those surviving for 7 days. CONCLUSIONS: These results
      demonstrate synergistic neuroprotective effects of citicoline and an NMDA
      antagonist in temporary experimental focal ischemia.

PMID- 9158651
TI  - Role of P-450 arachidonic acid epoxygenase in the response of cerebral blood flow
      to glutamate in rats.
AB  - BACKGROUND AND PURPOSE: Glutamate, a major excitatory neurotransmitter in the
      brain, has been implicated in the hyperemic response to increases in the activity
      of neurons, but the mechanism of glutamate-induced dilation of cerebral blood
      vessels is unknown. Glutamate has been shown to enhance the release of
      arachidonic acid (AA) in brain tissue and cultured astrocytes. We have previously
      shown that astrocytes metabolize AA to vasodilator products, epoxyeicostrienoic
      acids (EETs), and express a P-450 AA epoxygenase, P-450 2C11. We tested the
      hypothesis that glutamate-induced dilation of cerebral arterioles is mediated in
      part by changes in the formation and release of EETs by perivascular astrocytes.
      METHODS: Primary astrocyte cultures were prepared from 3-day-old rat pups. The
      cells were labeled with [14C]AA, and the effect of glutamate on the formation of
      EETs from [14C]AA by cultured astrocytes was studied. The expression of P-450
      2C11 protein in the microsomal fractions of cultured astrocytes was assessed by
      Western blot. In vivo cerebral blood flow measurements were made in adult rats by
      laser-Doppler flowmetry after administration of glutamate into the subdural space
      of the rat before and after treatment with miconazole. RESULTS: Glutamate
      treatment (100 mumol/L for 30 minutes) induced a threefold increase in the
      formation of EETs from [14C]AA by cultured astrocytes, and the increase was
      inhibited by miconazole (20 mumol/L), an inhibitor of P-450 AA epoxygenase.
      Treatment with glutamate (100 mumol/L) for 12 hours increased the expression of P
      450 2C11 protein in the microsomal fraction of cultured astrocytes. The response
      of laser-Doppler cerebral blood flow to administration of glutamate (500 mumol/L)
      into the subdural space of the rat was significantly attenuated after treatment
      with miconazole (20 mumol/L for 30 minutes). CONCLUSIONS: These findings suggest
      a role for a P-450 AA epoxygenase in astrocytes in the coupling between the
      metabolic activity of neurons and regional blood flow in the brain.

PMID- 9158652
TI  - Global ischemia activates nuclear factor-kappa B in forebrain neurons of rats.
AB  - BACKGROUND AND PURPOSE: After global ischemia, brain levels of hydrogen peroxide,
      oxygen radicals, and the cytokines tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1 beta (IL-1 beta) are increased. Oxygen radicals, TNF-alpha, and IL
      1 beta are known to activate nuclear factor-kappa B (NF-kappa B) in vitro. The
      present study was performed to determine whether NF-kappa B was activated in vivo
      by global ischemia in hippocampal CA1 neurons. METHODS: Adult male rats were
      subjected to 30 minutes of four-vessel occlusion and killed 72 hours later.
      Levels of NF-kappa B p50 and p65 subunits in hippocampus were determined by
      immunocytochemistry, Western blot, and gel-shift analysis. Specific labeling of
      DNA strand breaks was demonstrated by means of an Apoptag apoptosis detection
      kit. RESULTS: Labeling of DNA strand breaks was present at 72 hours. Chromatin
      compaction and segregation, a characteristic of apoptosis, was observed in
      sections stained with hematoxylin and eosin. NF-kappa B p50 and p65
      immunoreactivity localized only to nuclei of CA1 neurons at 72 hours after
      reperfusion. Induction of the activated p50 and p65 subunits was confirmed by
      Western blot and electromobility shift analysis. The results demonstrate that NF
      kappa B is activated selectively in hippocampal CA1 neurons at 72 hours after
      four-vessel occlusion, which is at the approximate time of CA1 neuronal cell
      death. CONCLUSIONS: Transient forebrain ischemia resulted in a marked activation
      of nuclear NF-kappa B in the highly vulnerable CA1 sector. Intense nuclear
      localization of NF-kappa B was associated only with dying neurons; regions of the
      hippocampus that were not vulnerable to four-vessel occlusion did not exhibit
      nuclear NF-kappa B localization. The elevation of NF-kappa B in degenerating CA1
      neurons may be associated mechanistically with apoptotic or necrotic cell death.

PMID- 9158653
TI  - Diffusion-weighted imaging discriminates between cytotoxic and vasogenic edema in
      a patient with eclampsia.
AB  - BACKGROUND: The pathophysiology of eclampsia remains unclear. While the majority
      of patients develop reversible T2 hyperintense signal abnormalities on MR scans
      and reversible neurological deficits, some patients do develop infarctions
      (permanent T2 hyperintense abnormalities) and permanent neurological impairment.
      Routine MRI cannot prospectively differentiate between these two patient groups.
      Echo-planar diffusion-weighted imaging, however, is a new technique that clearly
      differentiates between cytotoxic and vasogenic edema. CASE DESCRIPTION: A 30-year
      old woman developed symptoms consistent with eclampsia 24 hours after delivering
      premature twins. An MRI demonstrated extensive, diffuse T2 hyperintense signal
      abnormalities involving subcortical white matter and adjacent gray matter with a
      posterior predominance, consistent with either infarction or hypertensive
      ischemic encephalopathy. Diffusion-weighted images demonstrated increased
      diffusion, consistent with vasogenic edema and hypertensive ischemic
      encephalopathy. CONCLUSIONS: Unlike routine MRI, diffusion-weighted imaging
      reliably differentiates between vasogenic edema and cytotoxic edema.
      Consequently, in eclamptic patients diffusion-weighted imaging can afford clear
      differentiation between hypertensive ischemic encephalopathy and infarction, two
      very different entities with very different treatment protocols. Diffusion
      weighted imaging should be performed in all eclamptic patients and should greatly
      affect their management.

PMID- 9158654
TI  - What role do neurologists play in determining the costs and outcomes of stroke
      patients?

PMID- 9158655
TI  - When is thrombolysis justified in patients with acute ischemic stroke?

PMID- 9158656
TI  - Assessment of cerebral autoregulation using carotid artery compression.

PMID- 9158657
TI  - Clues to prevent cerebrovascular hazards of cysticidal drug therapy.

PMID- 9158658
TI  - Cytomegalovirus infection and restenosis.

PMID- 9158659
TI  - Rest perfusion of coiled aneurysms detected by transcranial color-coded duplex
      sonography: initial results.

PMID- 9158660
TI  - Serum levels of soluble IL-6 receptor in multiple myeloma as indicator of disease
      activity.
AB  - Serum soluble interleukin-6 receptor (sIL-6R) concentrations were measured in 50
      patients with plasma cell dyscrasias using a commercially available
      immunoenzymatic assay kit. There were 40 patients with multiple myeloma (MM), 5
      patients with monoclonal gammopathy of undetermined significance (MGUS), 3
      patients with solitary plasmacytoma (SPC), 1 patient with chronic myelogenous
      leukaemia and multiple myeloma (CML/MM), and 1 patient with plasma cell leukaemia
      (PCL). We found that serum sIL-6R concentrations were higher in MM patients
      (62.53 +/- 38.85 ng/ml) than in 20 normal volunteers studied (36.75 +/- 13.79
      ng/ml) (p < 0.01). The cut-off value of 65 ng/ml seen in 2 of our controls was
      arbitrarily taken as the upper limit of the control range for serum sIL-6R;
      according to this criterion, 14 patients with MM (35%), 1 patient with SPC, the
      unique patient with CML + MM, and the unique patient with PCL had elevated
      concentrations of the receptor. Patients with MGUS had normal sIL-6R values. In
      MM patients, serum sIL-6R levels correlated with the clinical phase of the
      disease: they were elevated in patients with early or late active disease and
      ranged within normal limits in patients with plateau-phase disease (p < 0.001).
      Thirteen of 27 patients with active MM had elevated serum sIL-6R values, i.e.
      48.1%, but only 1 out of 13 patients with disease in the plateau phase, i.e. 7.7%
      (p < 0.05). Furthermore, in the entire group of MM patients, serum sIL-6R levels
      correlated with the concentrations of serum beta 2-microglobulin, (p < 0.02), CRP
      (p < 0.01), ferritin (p < 0.01) and LDH (p < 0.01), while they did not correlate
      with disease stage, haemoglobin levels, proportion of marrow myeloma cells, the
      values of serum IL-6, the levels of serum albumin, or the grade of bone lesions.
      We conclude that elevated serum sIL-6R levels should be related to the growth of
      myeloma cells and suggest that serum sIL-6R concentrations may be used as an
      indicator of disease activity.

PMID- 9158661
TI  - Genotypic characterization and multivariate survival analysis of chronic
      lymphocytic leukemia in Taiwan.
AB  - In Taiwan, as in other areas of Asia, the incidence of chronic lymphocytic
      leukemia (CLL) is low. A retrospective analysis was conducted to elucidate the
      clinicopathologic features of CLL patients in Taiwan. Of the 47 cases of CLL
      enrolled in this study, 45 were immunophenotyped as B-CLL; the other 2 were T
      CLL. It was found that the lower the Binet and Rai stages of the B-CLL, the
      longer patients survive (p = 0.0131 and 0.0142, respectively). Univariate
      analysis showed that fatigue, splenomegaly, hepatomegaly and anemia are
      associated with poor survival with p values of 0.0203, 0.0184, 0.0001 and 0.171,
      respectively. By multivariate analysis with Cox's proportional hazard model,
      hepatomegaly and decrease in body weight were the two most significant predictors
      of survival. However, molecular parameters of kappa or lambda immunoglobulin (Ig)
      gene rearrangement or double allele rearrangement of Ig gene did not
      significantly increase the predictability of the prognosis.

PMID- 9158662
TI  - Relative levels of alpha-, beta-, and gamma-mRNA from patients with severe and
      intermediate beta-thalassemia major.
AB  - We have determined the relative quantities of gamma- and beta-mRNAs and the
      alpha/beta-mRNA ratios in 37 patients with beta-thalassemia major with specific
      genotypes, namely 8 with a homozygosity for codon (CD) 39 (C-->T), 7 with a
      homozygosity for IVS-I-110 (G-->A), 5 with a homozygosity for IVS-I-6 (T-->C),
      for 15 patients with compound heterozygosities for 2 of these 3 mutations, and
      for 2 patients with the IVS-I-110 (G-->A)/-87 (C-->G) mutations. None had an
      alpha-thalassemia. Twelve patients had thalassemia intermedia and the remainder,
      transfusion-dependent severe conditions. Differences in phenotype were observed
      for compound heterozygotes involving the IVS-I-6 (T-->C) mutation in combination
      with either the IVS-I-110 (G-->A) or the CD 39 (C-->T) mutations: patients with
      thalassemia intermedia had a lower alpha/beta-mRNA ratio, about half of that of
      the patients with severe beta-thalassemia major. This might suggest a higher beta
      mRNA synthesis in some patients than in others with the same genotype; mutations
      in promoter, enhancer, and/or locus control region sequences may be responsible
      for these differences. In vitro chain synthesis data were too incomplete to be
      helpful in this study. The RT-PCR procedure allowed the separation of abnormal
      (extended) mRNA from normal beta-RNA in subjects carrying the IVS-I-110 (G-->T)
      mutation. The relative quantities of this beta Th-mRNA (% of beta A + beta Th)
      were determined by scanning of the appropriate autoradiograms; they averaged 25%
      for homozygotes and about 4% for heterozygotes, indicating a considerable
      instability of the message.

PMID- 9158663
TI  - Effect of glucose-6-phosphate dehydrogenase deficiency on neutrophil function.
AB  - The bactericidal activity of neutrophils depends primarily on free oxygen
      radicals released by the activation of NADPH oxidase when neutrophils are
      stimulated by microorganisms. Severe glucose-6-phosphate dehydrogenase (G6PD)
      deficiency is associated with decreased NADPH production. Increased
      susceptibility to recurrent bacterial infections in children with severe
      neutrophil G6PD deficiency as a consequence of decreased NADPH production has
      been reported earlier. In this study, the in vitro activity of neutrophils from
      normal and G6PD-deficient individuals was assessed by measuring the [14C]CO2
      released via the hexose monophosphate shunt from radiolabeled [1-14C]-glucose and
      the nitroblue tetrazolium (NBT) dye reduction test. Our results show that the
      G6PD activity of neutrophils from 48 individuals, identified as severely
      erythrocyte (RBC) G6PD deficient (< 2 U/10(12) RBC) was 23% of the enzyme
      activity of neutrophils from 53 individuals with normal RBC G6PD levels (98.8
      U/10(12) RBC). However, the results of functional assays of neutrophils as
      measured by hexose monophosphate shunt and the NBT test were comparable in G6PD
      deficient and normal individuals, suggesting that a reduced activity of G6PD to
      as low as 23% of normal does not affect neutrophil function.

PMID- 9158664
TI  - The monosomy 7 clone in interphase and metaphase cell population: a combined
      chromosome and primed in situ labeling study.
AB  - Loss of a chromosome 7 is associated with a poor prognosis in acute myeloid
      leukemia (AML) and myelodysplastic syndromes (MDS). Some studies have shown
      higher frequencies of monosomy 7 (-7) in dividing than nondividing myeloid cells,
      which might indicate that -7 confers a proliferative advantage on the host cell.
      As other groups have not been able to confirm this, we compared the -7
      frequencies in bone marrow metaphases as studied with conventional cytogenetics
      and in interphase cells using primed in situ (PRINS) labeling. We found
      significantly higher -7 frequencies in metaphase than in interphase cells
      irrespective of diagnosis and presence or absence of additional chromosome
      aberrations. Further, we found a significant correlation between the -7
      percentages in resting and dividing cells. Finally, as our material showed a
      clear male preponderance, Mitelman's Catalog of Chromosome Aberrations in Cancer
      was searched for -7. Of 815 cases with AML or MDS, 491 (60.3%) were found to be
      men. To our knowledge, this is the first observation of a clear deviation from
      the 1:1 sex ratio in -7 patients.

PMID- 9158665
TI  - A case of interstitial pneumonitis associated with natural alpha-interferon
      therapy for myelofibrosis.
AB  - A 55-year-old man with myelofibrosis was treated with natural alpha-interferon
      with a good hematologic response. Initially, he had anemia, leukocytosis,
      thrombocytosis and hepatospleomegaly. A bone marrow biopsy showed replacement
      with fibrosis with an increase in megakaryocytes. Natural alpha-interferon (alpha
      IFN) was started at a dose of 3 x 10(6) units/day. The leukocyte and platelet
      counts gradually normalized, and the liver and spleen decreased in size. However,
      the patient complained of a dry cough and dyspnea on the 61st treatment day, when
      the accumulated dose of alpha-IFN treatment had reached 1.8 x 10(8) units. He
      subsequently developed acute respiratory failure (PaO2 < 60 mm Hg) with bilateral
      lung infiltrations, suggesting the occurrence of interstitial pneumonitis
      associated with alpha-interferon therapy. Immediately, the alpha-interferon was
      discontinued and high-dose methylprednisolone (1.5 g/day) was administered for 3
      days. This treatment was followed by oral prednisone therapy. Steroid therapy
      brought about gradual improvement as suggested by a repeat radiograph. Since high
      levels of fibrogenic cytokines, such as PDGF and TGF-beta, have been reported in
      patients with myelofibrosis, it is necessary to pay attention to interstitial
      pneumonia as a complication in alpha-IFN therapy for myelofibrosis.

PMID- 9158666
TI  - Follicular cell carcinoma of the thyroid in a child after bone marrow
      transplantation for acute lymphoblastic leukemia.
AB  - Follicular cell carcinoma (FCC) of the thyroid is rarely found during childhood.
      We report a 12 1/2-year-old girl with acute lymphoblastic leukemia, who developed
      rapidly growing FCC of the thyroid, 3 years after bone marrow transplantation.
      The role of chemotherapy in the induction of such secondary tumors after
      transplantation is discussed, and a proposal for the approach to these patients
      is suggested.

PMID- 9158667
TI  - Thrombotic complications in acute promyelocytic leukemia during all-trans
      retinoic acid therapy.
AB  - A case of acute renal failure, due to occlusion of renal vessels in a patient
      with acute promyelocytic leukemia (APL) treated with all-trans-retinoic acid
      (ATRA) and tranexamic acid has been described recently. We report a case of acute
      renal failure in an APL patient treated with ATRA alone. This case further
      supports the concern about thromboembolic complications associated with ATRA
      therapy in APL patients. The patients, a 43-year-old man, presented all the signs
      and symptoms of APL and was included in a treatment protocol with ATRA. After 10
      days of treatment, he developed acute renal failure that was completely
      reversible after complete remission of APL was achieved and therapy discontinued.
      We conclude that ATRA is a valid therapeutic choice for patients with APL,
      although the procoagulant tendency is not completely corrected. Thrombotic
      events, however, could be avoided by using low-dose heparin.

PMID- 9158668
TI  - Bilateral primary renal non-Hodgkin's lymphoma presenting with acute renal
      failure: successful treatment with systemic chemotherapy.
AB  - Primary renal non-Hodgkin's lymphoma (NHL) with acute renal failure is a very
      rare condition, which frequently occurs in bilateral renal involvement. We report
      a 26-year-old male with primary bilateral renal NHL presenting with acute renal
      failure. A CT scan of the abdomen showed markedly enlarged kidneys with
      multinodularity and para-aortic lymphadenopathy. A percutaneous renal biopsy
      demonstrated 'follicular center lymphoma, diffuse, small cell'. Thirteen cycles
      of systemic chemotherapy with cyclophosphamide-doxorubicin-vincristine
      prednisolone (CHOP) and ifosfamide-methotrexate-etoposide-bleomycin (IMVP-Bleo)
      regimens were administered, which resulted in normalization of renal function
      with improvement of renal lymphoma. Since there was no further change of renal
      lesions after initial partial remission, a follow-up renal biopsy was performed
      10 months after diagnosis, and no residual lymphoma was found.

PMID- 9158669
TI  - A case of hepatocellular carcinoma with marked hyperfibrinogenemia.
AB  - The present report concerns a case of hepatocellular carcinoma (HCC) with marked
      hyperfibrinogenemia. The plasma fibrinogen level reached as high as 1,704 mg/dl.
      Since treatment against HCC resulted in reduction of plasma fibrinogen and PIVKA
      II, an HCC marker, the hyperfibrinogenemia appears to be related to HCC.
      Immunohistochemically, the HCC specimen from this patient reacted strongly with
      antiserum to human fibrinogen, suggesting that the elevated fibrinogen was due to
      synthesis of this protein by the carcinoma cells, not to decreased fibrinolytic
      activity.

PMID- 9158670
TI  - Functional adrenocortical adenoma in a case with B cell chronic
      lymphoproliferative disorder.
AB  - We describe a B cell chronic lymphocytic leukemia/lymphoma (B-CLL) patient with
      an adrenocortical adenoma. He was treated initially with oral cyclophosphamide
      and prednisolone for 2 months, followed by low-dose prednisolone for an
      additional 2 years, which resulted in the prompt disappearance of CLL cells.
      After a period of 2 years without therapy, a functional adrenocortical adenoma
      was found. After adrenalectomy, the CLL cells rapidly increased. Progression of
      the disease and clinical-hematological relapse was well controlled by low doses
      of steroids alone, and the patient's condition stabilized. Considering the recent
      data that corticosteroids can induce apoptosis of CLL cells, the above clinical
      course suggests that augmented glucocorticoid production from the tumor may have
      suppressed disease progression.

PMID- 9158671
TI  - Full presence of Epstein-Bar virus (EBV)-encoded latent proteins in tissues from
      a patient with severe chronic active EBV infection syndrome.

PMID- 9158672
TI  - Haematopoietic cytokines and increased megakaryocytic proliferation in chromosome
      5q deletion.

PMID- 9158673
TI  - Synchronous mucosa-associated lymphoid tissue lymphoma and adenocarcinoma of the
      stomach.
AB  - The development of simultaneous primary gastric lymphoma and carcinoma is a rare
      event for which a possible etiopathogenetic role for Helicobacter pylori (HP)
      recently has been postulated. We report a series of eight such cases diagnosed
      from 1980 to 1995. In two cases, both tumors arose in a gastric stump, at 26 and
      34 years, respectively, after gastric resection for a duodenal ulcer. Grossly,
      the lymphoma and carcinoma formed a single lesion in four cases (collision
      tumor); they were separated in the other four cases. Histologically, all the
      lymphomas fit into the category of B-cell mucosa-associated lymphoid tissue
      lymphoma; six of them were low-grade lymphomas and two were low-grade lymphomas
      with a high-grade component. The adenocarcinomas were intestinal-type in four
      cases, diffuse in three, and mixed in one. Regarding the depth of infiltration,
      four carcinomas were early gastric cancers and four were advanced. All the
      collision tumors contained an early gastric cancer. Our observations confirmed
      the association of HP with gastric lymphoma and carcinoma in 4 cases. Spiral
      bacteria with the features of Helicobacter heilmannii were found in one case. The
      occurrence of two different tumors in a gastric stump, which has not been
      reported previously, suggests that postgastrectomy gastritis might contribute to
      the development of both gastric lymphoma and carcinoma.

PMID- 9158674
TI  - Transitional cell metaplasia of the uterine cervix and vagina: an underrecognized
      lesion that may be confused with high-grade dysplasia. A report of 59 cases.
AB  - Sixty-three examples of transitional cell metaplasia of the cervix or vagina from
      patients 50 to 84 (average 67.6) years of age are described. Fifty-seven of the
      59 patients were postmenopausal and two perimenopausal. Only four patients were
      documented to have received hormonal therapy. The lesion was an incidental
      microscopic finding in all patients and was found in 29 hysterectomy specimens,
      18 endocervical or endometrial curettage specimens, 11 cervical biopsy or cone
      biopsy specimens, and five vaginal biopsy specimens. The sites involved by
      transitional cell metaplasia were the exocervix (n = 14), transformation zone (n
      = 33), vagina (n = 10), or a combination (n = 4). The cervical and vaginal
      specimens most commonly showed involvement of the surface epithelium by
      transitional cell metaplasia. Other transitional cell patterns were isolated
      stromal nests (n = 9) and invagination of surface epithelium into the underlying
      stroma (n = 2). The typical appearance of transitional cell metaplasia was a
      hyperplastic epithelium with lack of maturation, consisting of spindled nuclei
      with tapered ends and frequent longitudinal nuclear grooves. The nuclei were
      typically oriented vertically in the deeper layers, and horizontally with a
      streaming pattern superficially. The cells had low nuclear to cytoplasmic ratios,
      perinuclear halos, and absent to rare mitotic figures. Mild to moderate atypia
      was seen in only two cases. Many of the cases could have been confused with
      squamous dysplasia due to the lack of apparent maturation. However, in most
      cases, attention to cytologic detail disclosed the typical features of
      transitional cell metaplasia. This process, usually seen in older women, has not
      been emphasized and can be overdiagnosed as dysplasia, leading to unnecessary
      treatment.

PMID- 9158675
TI  - Well-differentiated inflammatory liposarcoma: an uncommon and easily overlooked
      variant of a common sarcoma.
AB  - The presence of abundant inflammation is uncommon in well-differentiated
      liposarcomas (WDLPS). We describe ten cases of WDLPS in which an extensive
      lymphoplasmacytic infiltrate was present to such a degree that the differential
      diagnoses included inflammatory pseudotumor and Castleman's disease, and in which
      the lipogenic component could easily be overlooked. The median age (62 years) and
      tumor location (six retroperitoneal, three head/neck, one paratesticular) was
      comparable to usual WDLPS, as was the fact that six of ten cases recurred
      locally, but none metastasized during the period of follow-up (range 13 to 228
      months, median 72 months). Key histologic features included (1) nodular
      lymphoplasmacytic aggregates; (2) intervening paucicellular stroma containing
      fibroblastic elements, frequently with plasma cell-rich zones and scattered
      atypical, often multinucleate cells; (3) merging of atypical adipocytic and
      inflammatory elements; and (4) adjacent clearly defined zones of lipoma-like or,
      more rarely, sclerosing-type liposarcoma. In recurrences, two cases "reverted" to
      purely lipoma-like liposarcoma, and two cases dedifferentiated. Immunoperoxidase
      studies demonstrated that B cells predominated in the lymphoid aggregates, and
      that the abundant plasma cells were polytypic in nature. We support the use of
      the term well-differentiated inflammatory liposarcoma for tumors of this type,
      which should be distinguished from high-grade liposarcoma containing inflammatory
      cells, and in order to identify a subgroup of WDLPS at high risk for
      misdiagnosis.

PMID- 9158676
TI  - Transformation of follicular lymphoma into CD30-large cell lymphoma with
      anaplastic cytologic features.
AB  - The natural history of follicular lymphoma is to accrue large cells and become
      diffuse, resulting in progression/transformation to a higher-grade lymphoma.
      Histologic transformation occurs in approximately 60% of patients. Most often,
      follicular lymphomas transform into diffuse large cell lymphoma, but
      transformation to lymphomas classified using the Working Formulation as diffuse
      mixed, large cell immunoblastic, or small noncleaved cell also have been
      reported. Evidence of transformation may be found over time in sequential biopsy
      specimens, or may coexist in the same biopsy specimen. Here, we describe six
      cases of follicular lymphoma, large cell in five cases and mixed in one case,
      that transformed into a diffuse or sinusoidal CD30 antigen-positive large cell
      lymphoma with anaplastic cytologic features. Both the follicular and
      diffuse/sinusoidal components were of B-cell lineage, positive for the CD20
      antigen and negative for the CD3 and CD43 antigens. The neoplastic cells
      expressed monotypic immunoglobulin light chain in five cases, three kappa and two
      lambda. BCL-2 protein was positive in four tumors, in both the follicular and
      diffuse/sinusoidal components in three cases, and only in the latter component in
      one case. Using the polymerase chain reaction (PCR), three of six cases had
      monoclonal immunoglobulin heavy chain gene rearrangements. The t(14;18) was not
      amplified in any case. Using reverse transcriptase (RT)-PCR, the t(2;5) was
      amplified in one of four tumors. This report highlights the heterogeneity of B
      lineage anaplastic large cell lymphomas and indicates the need to consider
      antecedent follicular lymphoma in any B-cell lymphoma with anaplastic cytologic
      features.

PMID- 9158677
TI  - Fetal congenital cystic adenomatoid malformations of the lung: a
      clinicopathologic study of eleven cases.
AB  - We describe the pathological examination of 11 cases of fetal congenital cystic
      adenomatoid malformation of the lung. All patients were treated in utero between
      21 and 27 weeks of gestation with either lobectomy or placement of a
      thoracoamniotic shunt. Ten cases involved a single lobe, and one case involved
      two lobes. The lesions contained both solid and cystic areas. On the basis of
      microscopic appearances, we separated the malformations into two distinct types.
      The first type consisted of seven cases showing scattered bronchiole-like dilated
      spaces lined by pseudostratified ciliated epithelium with intervening tightly
      packed small tubules lined by columnar cells with subnuclear vacuoles. This
      pattern superficially resembled the pseudoglandular period of lung development.
      The remaining four cases were of the other histologic type. They contained
      scattered bronchiole-like structures with intervening irregularly branching
      glands lined by cuboidal epithelium within loose mesenchymal stroma. This pattern
      superficially resembled the canalicular period of lung development. We observed
      that the malformations contained cysts of various sizes and that cyst size varied
      widely within a single lesion. Moreover, predominantly cystic and predominantly
      solid lesions could not be separated histologically. Thus, we identify two
      patterns of fetal congenital cystic adenomatoid malformations, pseudoglandular
      and canalicular, the clinical significance of which is yet to be determined.

PMID- 9158678
TI  - Histologically distinctive papular neutrophilic xanthomas in HIV-1 + patients.
AB  - Xanthomas may be associated with benign or malignant lymphoproliferative
      diseases, often with associated hypergammaglobulinema. In human immunodeficiency
      virus type 1 (HIV-1) disease, there is a high lymphoproliferative rate despite
      the immunodeficiency and increased cell death. We report three HIV-1-positive
      patients with facial papular xanthomatosis eruptions associated with
      hypergammaglobulinema, and an immunoglobulin A (IgA) gammopathy. Histopathologic
      features include lipid-laden macrophages, extracellular nuclear dust with
      phagocytosized nuclear debris, and hyalinization with areas of hyaline necrosis
      of collagen fibers. These distinctive papular xanthomas may be a marker of HIV-1
      disease and of a pattern of immunodysregulation, immunodeficiency, and lymphoid
      proliferation seen in HIV-1 disease.

PMID- 9158679
TI  - Diagnosis of Cowper's glands on prostate needle biopsy.
AB  - The presence of normal anatomic structures may be a source of confusion to the
      pathologist examining prostatic needle biopsies. The morphologic features of
      Cowper's (bulbourethral) glands incidentally biopsied during transrectal sampling
      of the prostate have not been described. We reviewed seven cases of Cowper's
      glands found in prostatic core biopsy specimens. Sections containing Cowper's
      glands were stained with hematoxylin-eosin, mucicarmine, periodic acid-Schiff's
      digest (PAS-D), and antibodies directed at high-molecular-weight cytokeratin
      (HMWCK), prostate-specific acid phosphatase (PSAP), prostate-specific antigen
      (PSA), Ulex europaeus agglutinin, and muscle-specific actin. Histologically,
      Cowper's glands resemble mucinous minor salivary glands entrapped within
      fascicles of muscle. Lobules of acini composed of cells distended with mucin
      (mucicarmine and PAS-D positive) were admixed with ducts and ductules composed of
      hybrid cells with both mucinous and ductular epithelial features. The HMWCK was
      strongly reactive with the ductular epithelium and demonstrated an attenuated
      cell lining at the periphery of lobules. The mucinous cytoplasm reacted with U.
      europaeus, whereas the ductal elements failed to stain. PSAP stains were
      negative, with PSA positive in most cases. Muscle-specific actin was positive in
      three cases. Cowper's glands occasionally may be sampled by transrectal needle
      biopsy. Recognition of this anatomic structure will allow discrimination from low
      grade prostatic adenocarcinoma, foamy gland carcinoma, mucinous metaplasia of
      prostate glands, and atypical glands of undetermined significance.

PMID- 9158680
TI  - Adrenocortical neoplasms: role of prognostic markers MIB-1, P53, and RB.
AB  - Differentiation between benign and malignant adrenocortical neoplasms is made
      using a combination of clinical and pathologic parameters. Despite these
      parameters, it is still difficult to predict the biologic potential of some
      tumors. Forty adrenocortical lesions, including 10 hyperplasias, 10 adenomas, 12
      carcinomas and eight metastatic/recurrent adrenocortical carcinomas were studied
      for the expression of MiB-1, p53, and the retinoblastoma gene product (RB)
      utilizing immunohistochemical techniques. The mean tumor proliferating fraction
      (TPF), expressed as the number of MiB-1-positive nuclei per 1,000 tumor cells,
      was 14.9 in adenomas, 31.5 in hyperplasias, 208.1 in carcinomas and 166.1 in
      recurrent or metastatic disease. None of the 20 benign lesions had a TPF of > 80,
      and only one of the 20 malignancies had a TPF of < 80. Nine of the 20 carcinomas
      were positive for p53. None of the benign lesions were p53 positive. Thirty-nine
      cases, including benign and malignant ones, were RB positive, and one was
      uninterpretable. We conclude that prognostic markers can be of great assistance
      in recognizing adrenocortical carcinomas. High TPF (> 80), as measured by
      staining with MiB-1, and positive p53 strongly correlate with malignant behavior
      and therefore may be useful in distinguishing benign from malignant adrenal
      lesions. Staining for RB does not appear to be a helpful technique.

PMID- 9158681
TI  - Necrobiotic palisading suture granulomas involving bone and joint: report of two
      cases.
AB  - Biomaterial used in surgery is relatively inert and non-toxic; however, adverse
      reactions may follow implantation of such foreign material. We describe the first
      two cases of bone and joint destruction by necrobiotic palisading suture
      granulomas. The hypersensitivity reaction occurred years after shoulder repair
      using silk sutures. One patient received chemotherapy for a mistaken diagnosis of
      tuberculous arthritis. Although very rare, foreign material should be included in
      the differential diagnosis of necrotizing granulomas. A history of surgery and
      microscopic examination with polarized light should allow recognition of this
      entity.

PMID- 9158682
TI  - Correlation of prostate needle biopsy and radical prostatectomy Gleason grade in
      academic and community settings.
AB  - Prior studies have not analyzed grading patterns and accuracy in nonacademic
      sites and have not analyzed reasons for discrepant grades. We analyzed 499
      radical prostatectomy (RP) specimens at The Johns Hopkins Hospital (JHH) from
      1994 and compared them with the corresponding JHH needle biopsy Gleason grade
      and, when available (n = 390), to the outside institution (non-JHH) Gleason
      biopsy grade. For JHH, there was exact agreement between biopsy and RP in 58% and
      agreement to within one digit in 93% of cases, compared with 34% and 67%,
      respectively, for non-JHH. Combining cases into more meaningful groups (Gleason 2
      4, 5-6, 7, and 8-10), there was 66% exact correlation between the biopsy and RP
      for JHH as compared with 45% for non-JHH. Non-JHH undergraded biopsy results more
      than JHH, with 22.3% and 1.2% Gleason score 2-4, respectively. None of the cases
      with a Gleason score of 2-4 on biopsy from JHH or non-JHH were Gleason score 2-4
      on RP. Fifty-five percent of the tumors with non-JHH needle biopsy results graded
      Gleason 2-4 had either capsular penetration, seminal vesicle, or lymph node
      involvement. All of the tumors with needle Gleason score 2-4 at JHH were organ
      confined. The JHH needle biopsy grade correlated better with pathologic stage
      than did non-JHH (R = 0.27 JHH vs. R = 0.12 non-JHH). Extent of cancer in the
      biopsy sample was not a factor in the accuracy of predicting RP grade or stage.
      Eighty-two cases evaluated at JHH were signed out by a genitourinary pathologist;
      the grading of the biopsy samples by other JHH pathologists was just as accurate.
      Gleason score of > or = 7 on the biopsy sample predicted a Gleason score of > or
      = 7 in the RP 87.5% of the time. A Gleason score of < 7 predicted a Gleason score
      of < 7 only 63.9% of the time. Discordant grades in some cases reflected patterns
      of cancer on needle biopsy that were borderline between two different Gleason
      scores. Sampling was the major source of discrepancy and was often due to the
      high-grade component in the RP not being present in the biopsy results or due to
      a component of cancer on the needle reflecting such a small percentage of the
      pattern seen on RP that this pattern was not included in the final RP Gleason
      score.

PMID- 9158683
TI  - Chondromyxoid fibroma of the skull base: a tumor which may be confused with
      chordoma and chondrosarcoma. A report of three cases and review of the
      literature.
AB  - Three cases of chondromyxoid fibroma arising in the skull base are reported. The
      tumors arose in females 34, 65, and 66 (median 55) years of age. Two women
      presented with headaches, and one with nasal obstruction. Radiographic studies
      revealed that all three lesions were expansile soft tissue masses centered in the
      clivus, at least 4 cm in greatest diameter. One lesion involved primarily the
      clivus, the others extended from the clivus into the sphenoid and ethmoid
      sinuses. Two of the three cases were initially misdiagnosed as chordoma or
      chondrosarcoma. The initial treatment was curettage of gross disease in all three
      cases. One patient also received radiation therapy. One patient had local
      progression of disease, which was treated with surgery and radiation therapy. All
      patients are clinically free of disease 11 to 26 months following the most recent
      treatment. Chondromyxoid fibroma can and should be distinguished from
      chondrosarcoma and chordoma, two tumors which more commonly arise in the skull
      base and which have the potential to metastasize.

PMID- 9158684
TI  - Use of monoclonal antibody against human inhibin as a marker for sex cord-stromal
      tumors of the ovary.
AB  - Inhibin is a glycoprotein hormone produced by normal ovarian granulosa cells and
      testicular sertoli cells. In the ovary, it inhibits the secretion of follicle
      stimulating hormone. Patients with granulosa cell tumors (GCT) have elevated
      serum levels of inhibin and this finding has been used to detect recurrent tumor.
      This study attempts to determine whether inhibin antibody (IAB) can
      preferentially mark GCT and Sertoli-cell or Sertoli-Leydig cell tumors (SCT) in
      paraffin-embedded tissues and facilitate distinction of GCT from small cell
      carcinoma of hypercalcemic type (SCC), SCT from Sertoliform endometrioid
      carcinoma (SEC), and primitive gonadal-stromal tumors from a variety of poorly
      differentiated neoplasms. Applying microwave-enhanced immunohistochemistry, a
      total of 126 paraffin-embedded and microwave-enhanced archival ovarian tumors and
      tissues were studied by using monoclonal IAB. The tumors included 32 adult GCT, 7
      juvenile GCT, 4 metastatic GCT, 8 SCT, 7 SCC, 6 primitive gonadal stromal tumors
      (PGST), 5 fibrothecomas, 6 lipid cell tumors (LCT), 5 extrauterine endometrial
      stromal sarcomas (ESS), 5 hemangiopericytomas (HPC), 1 metastatic malignant
      melanoma, 1 metastatic malignant lymphoma, and 27 epithelial tumors including 8
      SEC, 5 mucinous tumors, and 4 Brenner tumors. Seven pregnancy luteomas (nodular
      theca lutein hyperplasia of pregnancy), 3 corpora lutea and 2 ovarian follicles
      were also studied. The intensity of immunostaining was scored from one to three
      and the percentage of the immunoreactive tumor cells was determined and expressed
      in 10% increments. Among 32 adult GCT, 31 (97%) tumors reacted positively with
      IAB. The percent of positive cells ranged from 30% to 100% (average 80%).
      Similarly, all four metastatic GCT, 7 juvenile GCT and 4 of 5 fibrothecomas were
      immunoreactive with monoclonal IAB. Seven of 8 (88%) SCT, 5 of 6 (83%) PGST, all
      6 LCT, 7 pregnancy luteomas, 3 corpora lutea and the 2 ovarian follicles were
      also positive with IAB. The most intense positivity was observed in luteinized
      stromal cells regardless of tumor type. No immunoreactivity was observed in any
      of the 7 SCC, 5 ESS, 5 HPC, 1 metastatic malignant melanoma, 1 metastatic
      malignant lymphoma and the epithelial component of all 27 epithelial tumors
      including 8 SEC. Among the mucinous tumors of the ovary, however, 3 tumors with
      luteinized stromal cells showed immunoreactivity in these cells, but no
      positivity was seen in the mucinous epithelium. We conclude that IAB is an
      excellent marker for sex cord differentiation in ovarian tumors. It can be used
      effectively in the diagnosis of GCT and its distinction from epithelial neoplasms
      particularly SCC. The IAB may also be helpful in differentiating LCT from
      epithelial malignancies. However, it cannot be used to distinguish GCT from SCT.

PMID- 9158685
TI  - Testicular and epididymal plasmacytoma: a report of 7 cases, including three that
      were the initial manifestation of plasma cell myeloma.
AB  - We report the cases of six men, 40 to 89 years of age, with testicular (6 cases)
      or epididymal (1 case) plasmacytoma. Patients presented with a mass in five
      cases. One tumor was found during evaluation of progressive myeloma. In the final
      case, the testicular lesion was identified when the patient presented with
      pathologic fractures. Gross inspection revealed discrete or, less often, ill
      defined lesions. Microscopic examination disclosed masses of atypical plasma
      cells, including binucleated and multinucleated cells and, occasionally,
      anaplastic cells that obliterated the underlying parenchyma or invaded between
      seminiferous or epididymal tubules. Immunohistochemical stains on paraffin
      sections in five cases showed tumor cell expression of monotypic cytoplasmic
      immunoglobulin. The cells were positive for the leukocyte common antigen (CD45)
      in three of five cases. All four cases tested were negative for B (CD20) and T
      (CD3) cell specific antigens and for CD30 and placental alkaline phosphatase.
      Expression of CD43, CD45RO, and epithelial membrane antigen was found in three,
      two, and one of four cases respectively. All the patients also had plasma cell
      neoplasia distant from the testis, identified before (3 cases), concurrent with
      (3 cases) or after (1 case) the testicular or epididymal plasmacytoma. In one
      patient a plasmacytoma developed in the contralateral testis three years later;
      he was alive with plasma cell myeloma 51 months after diagnosis. Another had a
      plasmacytoma in the contralateral epididymis 8 years later; he also had a nasal
      cavity plasmacytoma and multiple subcutaneous plasmacytomas, and was alive and
      well after 26 years. One additional patient was alive with myeloma 6 months
      later, and four final patients died between 2 months and 3 years after
      orchiectomy. Three of the four consultation cases in this series were submitted
      with diagnoses of spermatocytic seminoma, anaplastic seminoma and lymphoma. The
      diagnosis of plasmacytoma should be borne in mind when examining testicular or
      paratesticular tumors with a diffuse pattern without glandular differentiation,
      particularly in men 40 years of age or older.

PMID- 9158686
TI  - Epithelioid angiosarcoma of the breast. Clinicopathological, immunohistochemical,
      and ultrastructural study of a case.
AB  - A breast tumor with features of epithelioid angiosarcoma (EAS) occurring in a 26
      year-old woman is described. The lesion on lumpectomy was initially diagnosed as
      infiltrating ductal carcinoma and treated accordingly by radical mastectomy. The
      surgical specimen disclosed a high-grade tumor characterized by solid groups and
      sheets of atypical polygonal epithelioid cells displaying cytoplasmic microlumina
      alternating with anastomosing vascular channels. The endothelial nature of the
      epithelioid cells was demonstrated by the presence of vascular endothelium
      associated markers by immunohistochemical and ultrastructural studies. The
      clinical features of this rare, hitherto undescribed lesion are similar to those
      of conventional breast angiosarcoma. The recognition of this entity is crucial
      because it can be confused with neoplasms displaying epithelial cytomorphology
      such as ductal carcinoma, pseudoangiosarcomatous carcinoma, metaplastic
      carcinoma, and epithelioid hemangioendothelioma. EAS should be added to the list
      of conditions that may present as a discrete tumor mass of the breast in young
      women.

PMID- 9158687
TI  - Epidermization in the esophageal mucosa: unusual epithelial changes clearly
      detected by Lugol's staining.
AB  - A 58-year-old Japanese man with superficial esophageal cancer accompanied by
      unusual epithelial changes, including esophageal mucosal epidermization, is
      reported. Staining with Lugol's iodine clearly showed irregular unstained
      lesions, which could not be seen clearly macroscopically, in the resected
      specimen. Histologic examination of the irregular unstained areas showed definite
      granular and horny layers regarded as epidermization, acanthosis with slight
      nuclear enlargement, and epithelial atrophy. The immunohistochemical staining
      patterns of keratins in the epidermized and atrophic lesions were similar to
      those in the epidermis, and the keratin staining patterns of the acanthotic
      lesion were similar to those of the oral epithelium.

PMID- 9158688
TI  - Congenital pulmonary myofibroblastic tumor: a case report with cytogenetic
      analysis and review of the literature.
AB  - We report a case of congenital pulmonary myofibroblastic tumor, and review prior
      reports of this rare neoplasm to demonstrate its clinically benign behavior
      despite histologic features previously interpreted as sarcoma. The patient, a
      female neonate, presented with severe respiratory distress after cesarean section
      delivery. A large radio-opaque mass was detected in the right hemithorax and
      resected by right bilobectomy. The tumor mass, confined to the lung, was composed
      of interlacing fascicles of plump spindle cells showing myofibroblastic
      differentiation and complex cytogenetic abnormalities. Though sarcomatous in
      appearance, with highly cellular areas and numerous mitoses, there has been
      neither tumor recurrence nor metastases. The patient remains alive and well 1
      year after surgery. Review of the few other reported cases confirms the uniformly
      benign behavior of this tumor.

PMID- 9158689
TI  - Medullocytoma and glioneurocytoma: related tumors?

PMID- 9158690
TI  - Foamy gland carcinoma of the prostate.

PMID- 9158691
TI  - High sulfotransferase activity for phenolic aromatic odorants present in the
      mouse olfactory organ.
AB  - Mouse nasal cytosols show high sulfotransferase (ST) activities toward phenolic
      aromatic odorants, but have little activities for most alcoholic aromatic
      odorants. Most ST activities toward the phenolic odorants preferred slightly
      acidic pH (6.4) and were sensitive to 2,6-dichloro-4-nitrophenol, a specific
      inhibitor for phenol ST (P-ST) but were not inhibited by triethylamine and tetra
      n-butylammonium chloride, which are specific inhibitors for hydroxysteroid ST (HS
      ST). These results suggested that P-ST activities are responsible for sulfation
      of the phenolic odorants. The spectra of the ST activities for these odorants
      were similar in mouse nasal and liver cytosols, however, nasal cytosols showed
      much higher ST activity toward cinnamyl alcohol than liver cytosols. This
      activity preferred higher pH (7.4) compared to the phenolic odorant-ST activities
      and was inhibited by both types of inhibitors, specific for P-ST and HS-ST. These
      results appear to indicate the participation of multiple ST isoforms for the
      sulfation of odorants in mouse nasal cytosols. The existence of P-ST(s) active
      for the phenolic odorants in olfactory cytosols suggests a role in odorant
      perception, in particular, in the signal termination process.

PMID- 9158692
TI  - Oxidation of 4-alkylphenols and catechols by tyrosinase: ortho-substituents alter
      the mechanism of quinoid formation.
AB  - Numerous phenols and catechols are known to be substrates for tyrosinase. While
      the catalytic mechanism of phenol oxidation by tyrosinase has been well studied,
      little work has been done to determine the influence of substituents on the
      reaction. In the present investigation, we explored the effects of changing
      substituents at the 2 and 6 position on the mechanism of tyrosinase-catalyzed
      oxidation of 4-allyl and 4-propylphenols and catechols. We have previously
      demonstrated that tyrosinase initially oxidizes hydroxychavicol (4-allyl
      catechol) to an o-quinone (3,5-cyclohexadien-1,2-dione) which because of the
      relatively acidic protons in the benzyl position, readily isomerizes to the
      tautomeric p-quinone methide (4-allylidene-2,5-cyclohexadien-1-one, QM) (Bolton
      et al., 1994). We have confirmed through GSH trapping studies that oxidation of 4
      allylphenol by tyrosinase yields the same o-quinone GSH conjugates as
      hydroxychavicol. In contrast, the presence of additional ortho substituents
      dramatically alters the mechanism of tyrosinase-catalyzed oxidation of 4
      alkylphenols. For example, eugenol (4-allyl-2-methoxyphenol), which possesses 1
      ortho-methoxy substituents, is not oxidized to a o-quinone or a QM. However, when
      both ortho o-quinones or QMs which may be selectively toxic to the malignant
      melanocyte. Although mammalian tyrosinase is much more substrate specific
      compared to the mushroom tyrosinase used in this study [42], it should be
      possible to identify compounds which are substrates for the mammalian form but
      are otherwise oxidatively stable. In order to develop such target compounds an
      improved understanding of substituent effects on tyrosinase-catalyzed oxidation
      of catechols and phenols is necessary. This should for the development of
      strategies for therapeutic compounds that are selectively toxic toward melanoma.

PMID- 9158693
TI  - Prevention of lipid peroxidation induced by ochratoxin A in Vero cells in culture
      by several agents.
AB  - Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus ochraceus as well as
      other moulds. This mycotoxin contaminates animal feed and food and is nephrotoxic
      for all animal species studied so far. OTA is immunosuppressive, genotoxic,
      teratogenic and carcinogenic. It is a structural analogue of phenylalanine and
      contains a chlorinated dihydroisocoumarinic moiety. Ochratoxin A inhibits protein
      synthesis by competition with phenylalanine in the phenylalanine-tRNA
      aminoacylation reaction. Recently lipid peroxidation induced by OTA has been
      reported, indicating that the lesions induced by this toxin could also be related
      to oxidative damage. An attempt to prevent its toxic effect, mainly the lipid
      peroxidation, has been made using aspartame (L-aspartyl-L-phenylalanine methyl
      ester) a structural analogue of both OTA and phenylalanine, piroxicam, a non
      steroidal anti-inflammatory drug and superoxide dismutase+catalase (endogenous
      oxygen radical scavengers). Lipid peroxidation was assayed in monkey kidney cells
      (Vero cells) treated by increasing concentrations of OTA (5-50 microM). After 24
      h incubation OTA induced lipid peroxidation in Vero cells in a concentration
      dependent manner, as measured by malonaldehyde (MDA) production. The MDA
      production, in Vero cells, was significantly increased by 50.5% from 694.1 +/-
      21.0 to 1041.5 +/- 23.5 pmol/mg of protein. In the presence of superoxide
      dismutase (SOD)+catalase (25 micrograms/ml each) the MDA production induced by
      OTA was significantly decreased. At 50 microM of OTA concentration (optimal
      production of MDA) the MDA production decreased from 1041.5 +/- 23.5 to 827.5 +/-
      21.3 pmol/mg of protein. SOD and catalase, when applied prior to the toxin,
      seemed to prevent lipid peroxidation more efficiently than piroxicam (at a ten
      fold higher concentration than OTA) and aspartame (at equimolar concentration).
      These molecules also partially prevented the OTA-induced leakage of MDA in the
      culture medium.

PMID- 9158694
TI  - Comparison of 32P-postlabeling and HPLC-FD analysis of DNA adducts in rats
      acutely exposed to benzo(a)pyrene.
AB  - DNA adduct analysis is often used for biomonitoring individuals exposed to
      polycyclic aromatic hydrocarbons (PAH). The 32P-postlabeling assay is routinely
      applied to study the formation of aromatic bulky adducts, but cannot positively
      identify individual adduct types. Recently, an HPLC assay with fluorescence
      detection (HPLC-FD) was developed which was sufficiently sensitive to detect
      adducts formed by benzo[a]pyrene (B[a]P) diolepoxide isomers [(+/-)anti- and (+/
      )syn-BPDE] in occupationally exposed subjects (Rojas et al. Carcinogenesis, 16
      (1995) 1373-1376). In this study, we compared both techniques using DNA samples
      of rats which were treated i.p. with B[a]P (10 mg/kg bw). The internal dose was
      assessed by measuring 3-OH-B[a]P excretion in urine. The detection limit of the
      HPLC-FD assay varied from 0.5 to 7.4 adducts per 10(8) nucleotides, while the
      detection limit of the 32P-postlabeling assay was around 1 adduct per 10(9)
      nucleotides. HPLC-FD analysis showed that BPDE-DNA adduct levels were highest in
      the heart, lung and liver respectively. The most predominant B[a]P-tetrol was the
      I-1 isomer, which derives from hydrolysis of the major reaction product of DNA
      and (+)-anti-BPDE. 32P-postlabeling analysis revealed an adduct spot that
      comigrated with a [3H]BPDE-DNA standard. The putative BPDE-DNA adduct levels were
      highest in heart followed by lung and liver and correlated significantly with
      tetrol I-1 levels determined by HPLC-FD (r = 0.72, P = 0.006). In samples in
      which both tetrol I-1 and II-2 were detected by means of HPLC-FD, this
      correlation was even better (r = 0.95, P = 0.01). Estimated half-lives of BPDE
      DNA adducts were in the ranking order; heart, lung and liver for both techniques.
      By 32P-postlabeling, adducts other than BPDE-DNA were also found, resulting in
      highest total DNA adduct levels in the liver, heart and lung respectively.
      Furthermore, mean 24 h urinary excretion of 3-OH-B[a]P was related to BPDE-DNA
      adduct levels in lung, liver and heart. The 32P-postlabeling assay is sensitive
      and capable of detecting exposures to complex mixtures, whereas the HPLC-FD assay
      can be used to identify BPDE-isomers and might therefore be of value in risk
      assessment of individuals exposed to PAH.

PMID- 9158696
TI  - Assessment of pathology instruction.

PMID- 9158695
TI  - Estrogenic effects of nonylphenol on pS2, ER and MUC1 gene expression in human
      breast cancer cells-MCF-7.
AB  - Many chemicals have recently been discovered to have estrogenic activity,
      including the surfactant intermediate nonylphenol (NP). It has been well
      documented that estrogen is a facilitator of human breast cancer development
      under certain conditions, and environmental estrogens such as NP are currently
      under intense investigation. Using the expression of pS2 (a trefoil peptide
      expressed in breast cancer cells), MUC1 (a member of the mucin family) and ER
      (the human estrogen receptor) genes as estrogen-responsive reporter genes, the
      effects of estradiol and NP on human breast cancer cells-MCF-7 were studied. In
      the time course study, the mRNA expressions were detected after NP (10 microM) or
      estradiol (E2, 0.1 microM) treatments using the RT-PCR technique. The results
      indicated: (1) NP and E2 induced pS2 mRNA expression after a 2-h exposure and (2)
      NP induction produced the highest level of MUC1 mRNA after 2 h, which was reduced
      to only 42% of control at 48 h. E2 treatment resulted in a gradual increase in
      MUC1 expression over the course of the exposure. The highest level of MUC1 mRNA
      was at 48 h. This indicates that NP may stimulate MUC1 expression by a different
      mechanism than E2. (3) NP affected ER expression in the same manner as MUC1. In
      contrast, E2 stimulated ER expression in a similar manner as pS2; the highest
      level was at 2 h and expression remained elevated through the 48-h point. NP is
      an estrogenic compound that alters pS2, MUC1 and ER gene expression in MCF-7
      cells. NP may affect MUC1 expression through a different mechanism than E2. The
      link between aberrant MUC1, PS2 and ER expression and the development of breast
      cancer also needs to be elucidated through further investigation.

PMID- 9158697
TI  - The pathobiography and death of Wolfgang Amadeus Mozart: from legend to reality.
AB  - Mozart, perhaps one of the greatest geniuses of modern age, died mysteriously at
      the age of 35 in Vienna in 1791. The causes of his death are still somewhat
      obscure and debated since we do not have any documentation acceptable by current
      scientific standards. Inevitably, the conclusions reached are highly debatable.
      In the present article the various interpretations of Mozart's death are taken
      into consideration-from his possible poisoning to causes of death more acceptable
      by the present diagnostic criteria. We suggest that the terminal cause of death
      was brain hemorrhaging or stroke, complicated by broncopneumonia and associated
      with renal failure induced by proliferative glomerulonephritis and
      glomerulosclerosis.

PMID- 9158698
TI  - Relationship of students' perceptions of faculty to scholastic achievement: are
      popular instructors better educators?
AB  - Student evaluation of the faculty is a standard practice in most medical schools.
      Implied in these evaluations is the motion that popular instructors (ie, those
      considered outstanding by the students) are better educators, whose teaching
      translates into higher scores for their students on examinations. We tested this
      hypothesis by comparing students' evaluations of the faculty with levels of
      academic achievement in a second-year pathology course. Objective measures of
      academic achievement included scores on final comprehensive examinations, final
      course grade, and performance on the United States Medical Licensing Examination
      (USMLE). During the 4 years studied (1990 to 1995), students belonging to groups
      with the highest ratings for their instruction performed no better than those
      with the poorest ratings. There was no correlation between students' perceptions
      of quality in teaching and their academic achievement. Our results indicate that
      students' evaluations of the faculty are subjective and do not correlate with
      objective results used in the assessment of student knowledge. Popular
      instructors are not necessarily better educators.

PMID- 9158699
TI  - The virtues of extended matching and uncued tests as alternatives to multiple
      choice questions.
AB  - The objectives of this study were to compare the reliability and validity of
      written test formats that are widely used in medical education (multiple choice,
      uncued, extended matching, and true/false) and evaluate the effects of uncued
      examinations on long-term retention of medical knowledge. Uncued tests were
      introduced into a traditional course in general and systemic pathology (six
      interim tests). In the following year, students were given eight tests written in
      the four formats, each being used twice. The academic achievement of students in
      these 2 years was compared with that of students in 2 previous years, in which
      multiple choice tests were used. Measures of academic achievement included
      performance on a final comprehensive examination and the United States Medical
      Licensing Examination (USMLE). Student performance on uncued tests was consistent
      over time (i.e., there was no learning curve). Mean scores ranged from 77% to
      84%, and coefficient alpha reliability estimates on 100-item tests were excellent
      (0.79 to 0.90). Extended matching tests were also reliable, with a mean
      coefficient alpha of 0.90. There was no significant relationship between test
      format and student performance on subsequent comprehensive examinations. Our
      results indicate that extended matching and uncued tests have considerable
      advantages over multiple choice and true/false examinations. They are more
      reliable, better able to discriminate the well-prepared from the marginal
      student, and well suited for tested core knowledge. Contrary to our expectation,
      extended matching questions with 20 choices presented to the student were as
      statistically reliable and valid as uncued queries with several hundred choices.

PMID- 9158700
TI  - Posttransplant lymphoproliferative disorder in liver allograft biopsies: a
      comparison of three methods for the demonstration of Epstein-Barr virus.
AB  - Posttransplant lymphoproliferative disorder (PTLD) is associated with Epstein
      Barr virus (EBV), and may clinically resemble acute allograft rejection. Three
      methods to show EBV in tissue were evaluated in 15 liver allograft biopsies from
      12 patients including four with PTLD: (1) semiquantitative polymerase chain
      reaction (PCR) for EBV DNA; (2) in situ hybridization for EBV RNA (EBER); and (3)
      immunoperoxidase for EBV latent membrane protein (LMP). Index cases had a PCR dot
      blot result of "positive" or "weak positive." Findings were correlated with
      histology, clinical data, therapy, and outcome. All four PTLD patients had a
      clinical diagnosis of acute rejection. All four showed EBV: PCR 4, EBER 4, LMP 3,
      Liver function tests were elevated in three, but EBV viral capsid antigen (VCA)
      IgM was not increased in three, but EBV viral capsid antigen (VCA) IgM was not
      increased in three. Immunosuppression was withdrawn and all four patients
      underwent a second transplantation. One died 4 days posttransplant with
      disseminated PTLD, two died of sepsis at 1.5 and 14 months, and one is well at 3
      years without PTLD. Eleven biopsies without PTLD showed: acute rejection 7, acute
      rejection and hepatitis 1, hepatitis B 1, and non-inflammatory changes 2. In this
      group, EBV results included: PCR weak positive in 10 and 1+ in one, EBER negative
      in ten and rare positive cells in one, LMP negative in 11. Liver function tests
      were elevated in 10, whereas VCA IgM was not increased in three and increased in
      one. Patients with acute rejection were treated with increased immunosuppression:
      none developed PTLD, with follow-up of at least 6 months in nine cases. Two
      patients died within 4 months of biopsy. One patient with PTLD in tonsils had a
      liver biopsy showing both acute rejection and EBV (PCR 1+, rare EBER + small
      cells). Histological studies combined with special EBV detection methods, can be
      useful to evaluate atypical lymphoid infiltrates in liver allograft biopsies and
      confirmation of a diagnosis of PTLD. All three methods are useful; EBER and PCR
      are the most sensitive. EBER and LMP can use paraffin sections.

PMID- 9158701
TI  - von Hippel-Lindau gene deletion detected in the stromal cell component of a
      cerebellar hemangioblastoma associated with von Hippel-Lindau disease.
AB  - Central nervous system hemangioblastoma is a neoplasm with characteristic and
      well-described histopathological features, including proliferation of vascular
      and stromal cells. yet, the histogenesis of the stromal cell component and its
      neoplastic capacity as compared with the vascular component are still
      controversial. Stromal cells were selectively procured from formalin-fixed,
      paraffin-embedded archival tissue from a von Hippel-Lindau (VHL) disease patient
      with a cerebellar hemangioblastoma and studied for loss of heterozygosity (LOH)
      of the VHL gene locus and associated microsatellite regions. The stromal cells
      consistently showed LOH. Analysis of mixed stromal anti vascular areas of this
      tumor and four other hemangioblastomas of VHL patients showed that loss of
      heterozygosity was partially obscured. These preliminary results suggest that the
      stromal component of hemangioblastomas contains genetic alterations consistent
      with a neoplastic nature. Additional samples of pure stromal cells need to be
      analyzed to establish the prevalence of VHL gene deletion in stromal cells of
      capillary hemangioblastoma and, hence, its pathogenetic significance.

PMID- 9158702
TI  - Association of p53 protein expression in stage I lung adenocarcinoma with
      reference to cytological subtypes.
AB  - Since the nuclear accumulation of p53 protein is known to correspond well with
      mutation of the p53 tumor-suppressor gene, we analyzed the p53 protein
      immunohistochemically with the anti-p53 mouse monoclonal antibody, DO-7, in 105
      stage I lung adenocarcinomas. The p53 immunoreactivity was detected in the nuclei
      of cancer cells in 51 cases (49%). The p53-positive cases had a significantly
      poorer prognosis compared with the p53-negative cases (log-rank test; P < .001)
      When p53 expression was compared among the cytological subtypes of
      adenocarcinoma, the incidence of p53 expression in the bronchial surface
      epithelial cell type (11 of 15) was significantly higher than in the goblet cell
      type (1 of 6) and tended to be higher than the Clara cell/alveolar type II
      pneumocyte type (27 of 59). These findings indicate that immunohistochemical
      examination of the p53 protein is a potential prognostic factor in stage 1 lung
      adenocarcinomas, and that p53 expression has been associated with the cytological
      subtype.

PMID- 9158703
TI  - A study of p53 protein, proliferating cell nuclear antigen, and p21 in Hodgkin's
      disease at presentation and relapse.
AB  - About one fourth of patients with Hodgkin's disease relapse after therapy. The
      mechanisms that lead to resistance to treatment in these patients are poorly
      understood. The authors describe the differential protein expression of p53,
      proliferating cell nuclear antigen (PCNA), and p21 at initial presentation and
      relapse, and discuss their role in disease progression and resistance to therapy.
      Thirty-four patients with Hodgkin's disease who had relapsed after standard
      chemotherapy and radiotherapy regimens were assessed for the expression of p53
      protein, PCNA, and p21 protein (waf/cip 1). In 14 of these cases, sequential
      biopsies performed both at presentation and at relapse were available for the
      study. Seventy-five percent of the cases were positive for the p53 protein.
      Tumors at relapse had higher p53 and PCNA scores than those at initial
      presentation. In the paired samples, a significant increase was noted in the
      number of p53 and PCNA-positive cells and in the intensity of staining with p53
      antibody. Six of seven paired samples tested for p21 showed an increased p21
      expression at relapse. These results suggest that, at relapse, Reed-Sternberg
      (RS) cells and their variants positive for p53, PCNA, and p21 are increased in
      number and individually have an increased expression of p53, PCNA, and p21
      proteins. These findings suggest that therapy failure and relapse may, at least
      in part, be associated with altered p53, p21, and PCNA pathways. HUM PATHOL
      28:549-555. This work was carried out during an exchange fellowship program at
      the National Cancer Institute, Bethesda. There are no restrictions on its use

PMID- 9158704
TI  - Analysis of bcl-2 expression in normal, inflamed, dysplastic nasopharyngeal
      epithelia, and nasopharyngeal carcinoma: association with p53 expression.
AB  - To further characterize bcl-2 expression in nasopharyngeal carcinoma (NPC), the
      authors analyzed bcl-2 expression immunohistochemically in biopsy specimens from
      101 cases of NPC, of which 65 had the component of normal nasopharyngeal
      epithelium (NPE), 24 with dysplastic lesions adjacent to carcinoma, and 14 with
      both primary and metastatic lesions. An additional 25 nasopharyngeal biopsies of
      NPE from patients with chronic inflammation of nasopharynx were also included.
      The percentage of detectable bcl-2 expression shown in NPC (80%) and adjacent
      dysplastic lesions (71%) was significantly higher than in adjacent NPE (37%) and
      NPE from patients with chronic inflammation of the nasopharynx (30%) (P < .05).
      In both normal and inflamed NPE, the detectable bcl-2 expression was restricted
      to the basal cells; however, in dysplastic lesions, the bcl-2 staining
      distribution was increased with the dysplastic cell layers, and in entire layers
      of epithelium in severe dysplasia or carcinoma in situ. In addition, the staining
      intensity of bcl-2 in carcinomas and adjacent dysplastic lesions was generally
      stronger than that of adjacent NPE. These observations suggest that the
      expression of bcl-2 in dysplasia and carcinoma is enhanced relative to that of
      adjacent NPE. Enhanced bcl-2 expression to prevent apoptosis seems to occur from
      the early stages and may play an important role in the carcinogenesis of NPC.
      Furthermore, up to 77% of NPC with the coexpression of bcl-2 and p53 was observed
      and suggested that the association of bcl-2 and p53 expression seems to occur
      from the early stages of the development of NPC. The overexpression of p53
      protein in NPC suggests that the mutation of p53 gene or altered function of wild
      type p53 protein may contribute to the pathogenesis. It is conceivable that the
      presence of both enhanced bcl-2 expression and altered p53 functions may play a
      crucial synergistic effect in the carcinogenesis of NPC.

PMID- 9158705
TI  - Physiology and pathophysiology of dendritic cells.
AB  - Dendritic cells are antigen-presenting cells derived from the hematopoietic stem
      cell. The dendritic cell family includes Langerhans' cells (CD1a-positive
      dendritic cells of the skin), and antigen-presenting cells that are found in the
      lymphoreticular system and throughout the organ parenchyme. Dendritic cells play
      a key role in both the primary and secondary immune responses. Several studies
      indicate that these cells participate in antitumor immunity, tumor surveillance,
      graft-versus-host disease, and in the pathogenesis of clinical syndromes of
      unknown origin or those induced by viruses, such as the human immunodeficiency
      virus. Different disorders are characterized by an abnormal proliferation and
      accumulation of dendritic cells; for example, the Langerhans' histiocytes, which
      accumulate in Langerhans' cell histiocytosis. In this review the
      immunophenotypic, morphological, and functional characteristics of the dendritic
      cell family is described. The clinical and laboratory studies suggesting a unique
      role for these cells in various syndromes and diseases are reviewed. The
      Langerhans' cell histiocytoses and the malignant disorders associated with
      transformation of cells belonging to the dendritic cell family, are discussed.

PMID- 9158706
TI  - Pathological and immunophenotypic features of adult non-Hodgkin's lymphomas by
      age group.
AB  - To elucidate age-related differences in non-Hodgkin's lymphoma (NHL), the authors
      evaluated 950 consecutive, human immunodeficiency virus-negative patients (age
      range, 15 to 96 years) observed between July 1988 and June 1995 in the same
      Italian cancer institute. Patients were grouped into six age groups and cross
      tabulated by Working Formulation (WF) categories and other newly recognized
      entities according to the Revised European American Lymphoma (REAL)
      classification, cell immunophenotype, and nodal or extranodal location. There was
      a tendency of the low-grade category to increase with increasing age (16.8% in
      the age group 15 to 34 years to 32.4% in the age group 65 to 74 years), although
      a subsequent decline was seen at age 75 years or older (23.2%). Also the
      intermediate-grade category was more frequent in the elderly (46.6% and 49.4% at
      65 to 74 years and at 75 years or older, respectively). High-grade category
      showed compared with low and intermediate grade ones, a significant downward
      trend with age (X2 for trend = 25.31; P < .001), interrupted in only the oldest
      age group. The relative excess of low-grade NHL in patients older than 55 years.
      of age was accounted for by the high proportion of small lymphocytic lymphomas,
      which, however, somewhat declined at age 75 years or older. Conversely, the
      relative excess of high-grade NHL below age 35 years chiefly derived from the
      high percentage (28.4%) of CD30-positive anaplastic large cell lymphomas. B- and
      T-cell lymphomas accounted for 85.9% and 9.0% of all cases, respectively. B- and
      T- and non-B, non-T-cell and histiocytic NHL accounted for the remaining 5.1%. A
      highly significant trend of increase in the proportion of B-cell lymphomas with
      age increase was noted (X2 for trend = 21.90; P < .001); chiefly attributable to
      the excess of T-cell (15.1%) and undetermined phenotype (18.6%) in patients
      younger than 35 years of age. Extranodal location was not significantly related
      to age groups. Thus, the present study showed some interesting differences in NHL
      morphology and cell phenotype according to age, avoiding, at the same time, the
      arbitrariness of patients' dichotomization into elderly and nonelderly.

PMID- 9158707
TI  - Malignant cartilaginous tumors of the mediastinum: clinicopathological study of
      six cases presenting as extraskeletal soft tissue masses.
AB  - Cartilage and bone-forming tumors of the mediastinum are extremely rare neoplasms
      with very few cases having been reported in the literature. We studied six cases
      of primary malignant cartilaginous tumors presenting as extraskeletal soft tissue
      masses in the posterior mediastinum. The patients were five women and one man
      aged 11 to 63 years (median, 31 years). Histologically, the lesions showed a
      spectrum of features that ranged from mesenchymal chondrosarcoma, to
      extraskeletal myxoid chondrosarcoma, to moderately well to poorly differentiated
      chondrosarcoma. In all cases, the lesions presented as well-circumscribed tumor
      masses centered in the soft tissues in the posterior mediastinum without
      radiographic evidence of origin from bone. Because of their relatively small
      size, good circumscription, focal areas of calcification, and posterior
      mediastinal location, the preoperative clinical diagnoses included benign
      neurogenic tumor and neuroblastoma. All of the lesions were treated by complete
      surgical excision, followed in two cases by postoperative radiation therapy.
      Clinical follow-up was available in five cases: two patients with mesenchymal
      chondrosarcoma presented with local recurrence after 3 and 7 years, one developed
      metastases to the sacrum 8 years after initial diagnosis and died, and one was
      alive and well without evidence of disease after 6 years. The patient with myxoid
      chondrosarcoma of the posterior mediastinum developed bilateral pulmonary
      metastases 10 months after surgery and has been lost to follow-up since. Our
      findings reinforce previous observations on the occurrence of extraskeletal
      cartilaginous tumors in the mediastinum and indicate that these tumors can show a
      propensity for local aggressive behavior with high recurrence rate and a definite
      potential for distant metastases. Such tumors should be considered in the
      differential diagnosis of malignant neoplasms presenting as a soft tissue mass in
      the posterior mediastinum.

PMID- 9158709
TI  - Calcified amorphous tumor of the heart (cardiac CAT).
AB  - Eleven cases of poorly characterized nonneoplastic endocardially based
      intracavitary cardiac masses have been seen at the Mayo Clinic between 1965 and
      1994. They occurred in 7 women and 4 men from age 16 to 75 years (mean, 52
      years). The patients presented with a wide variety of symptoms and underlying
      diseases. The lesions were diagnosed as a primary cardiac neoplasm in 6 of 8
      patients having echocardiography. Surgical excision was the treatment of choice
      in 10 patients; the 11th patient died of noncardiac causes 30 days after the mass
      was discovered. Grossly, the lesions were firm, yellow-white, and partially
      calcified, and arose in any of the four chambers. Microscopically, all lesions
      were characterized by nodular calcium in a background of degenerating blood
      elements and chronic inflammation. All patients had a benign course relative to
      their cardiac lesion. Repeat echocardiogram in two patients showed residual
      calcium in the region of the initial tumor. Although these lesions may represent
      calcified thrombi, the clinical presentation did not suggest thrombosis as the
      most likely explanation for their occurrence. Based on the combined clinical
      presentation and microscopic appearance, the authors propose the descriptive name
      calcified amorphous tumors (cardiac CAT) to describe this group to nonneoplastic
      cardiac masses.

PMID- 9158708
TI  - Well-differentiated acinic cell carcinoma of salivary glands associated with
      lymphoid stroma.
AB  - In a multicenter study, 69 acinic cell carcinomas of the salivary glands were
      identified, of which 12 constituted what the authors believe to be a distinct
      subgroup. Their most noticeable feature was a dense lymphoid stroma with well
      developed germinal centers, surrounding a sometimes scanty epithelial component,
      which in each case had a microcystic growth pattern. All these tumors were
      enveloped by a thin fibrous pseudocapsule, thus mimicking an intraparotid lymph
      node containing a metastasis. All 12 cases showed low MIB1 proliferative
      activity, with a mean index of 1.7% (range, 0.5 to 3.7). All patients remained
      well without recurrence or metastasis in followup periods of 19 months to 14
      years. A second subgroup of nine acinic cell carcinomas also possessed a heavy
      lymphoid stroma with germinal centers, but its distribution was more patchy than
      in the first subgroup, and in addition, the fibrous pseudo-capsule was incomplete
      or absent. In each case the epithelial growth pattern was other than microcystic.
      These tumors had significantly higher MIB1 indices (mean, 17%; range, 3.4 to 45).
      In contrast to the first subgroup, only three of nine patients remained well with
      no further disease. The other six patients developed recurrences or metastases,
      and two died of disseminated cancer. In view of the clinical and pathological
      data, it is speculated that the tumor foci lacking lymphoid stroma in each of the
      second subgroup possibly represented a clone of high-grade malignancy arising
      within a low-grade acinic cell carcinoma with lymphoid stroma.

PMID- 9158710
TI  - Loss of heterozygosity in usual and special variant carcinomas of the
      endometrium.
AB  - Endometrial carcinoma is the most common invasive malignancy of the female
      genital tract, and it exists as two different clinicopathologic forms: an
      estrogen-dependent, "usual" type and an estrogen-independent "special variant"
      type. Despite the frequency of endometrial cancer, little is known about the
      molecular genetic events that contribute to its pathogenesis. The accumulation of
      genetic alterations identified through the study of loss of heterozygosity (LOH),
      gene mutation, and gene activation in tumor DNA has been associated with the
      establishment and progression of a variety of human malignancies. A relatively
      low incidence of LOH has been reported in usual type endometrial cancers;
      however, special variant tumors have rarely been included in the reported
      studies. To understand the molecular events that contribute to both forms of
      endometrial cancer, 31 tumors have been surveyed for events of LOH on all
      chromosomes. The study groups included 18 tumors of the usual type and 13 special
      variant tumors. Polymorphic loci were studied by Southern blot analysis and
      polymerase chain reaction (PCR) of microsatellite loci. Normal tissue in each
      case served as a control. Both frequency and patterns of LOH differed greatly
      between the two tumor types. Although LOH was frequently detected in the special
      variant tumors, it was rare in the usual type tumors. LOH was detected in only 8
      of the 18 usual tumors, with chromosomes 17, 13, and 2 being the most frequently
      affected (22%, 20%, and 19%, respectively). In contrast, LOH was detected in all
      cases of special variant tumors, with chromosomes 17p, 14, and 12 showing the
      highest LOH (83%, 77%, and 40%, respectively). Two cases of microsatellite
      instability (MI) were detected among the usual type tumors. These findings
      suggest that the clinicopathologic phenotypes observed in these tumor types are
      likely caused by different tumorigenic pathways that reflect alterations of
      different cancer-controlling genes.

PMID- 9158711
TI  - Expression of gelatinase A, tissue inhibitor of metalloproteinases-2, matrilysin,
      and trypsin(ogen) in lung neoplasms: an immunohistochemical study.
AB  - Lung cancer is a heterogeneous tumor in terms of clinical and biological
      behavior, and its aggressiveness depends on its invasive and metastatic
      properties. Matrix metalloproteinases and serine proteinases are believed to play
      a crucial role in invasion and metastasis of malignant tumor cells. In the
      present study, the authors evaluated immunohistochemically the expression of
      gelatinase A; tissue inhibitor of metalloproteinases-2 (TIMP-2), an inhibitor of
      gelatinase A; matrilysin; and trypsin(ogen) in 67 lung tumors from a variety of
      histological types including 17 squamous cell carcinomas, 16 adenocarcinomas, 15
      small cell carcinomas, and 12 carcinoids. Interestingly, normal bronchial,
      bronchiolar, and alveolar epithelial cells expressed gelatinase A, TIMP-2,
      matrilysin, and trypsin(ogen) at varying frequencies and intensities. Bronchial
      smooth muscle cells and cartilage cells expressed gelatinase A alone, whereas
      endothelial cells, fibroblasts, and macrophages expressed gelatinase A and TIMP
      2. Gelatinase A was expressed at high levels in most lung tumors examined (47% to
      80%). TIMP-2 was also expressed at high levels except in the small cell
      carcinomas, which showed TIMP-2 expression at a lower frequency (60%) compared
      with other types of lung tumors (80% to 100%). Although matrilysin was expressed
      by tumor cells of all the histological types at various frequencies (13% to 63%),
      its expression was most common in adenocarcinomas. Expression of trypsin(ogen)
      was observed almost exclusively in adenocarcinomas (56%); other types of lung
      tumors expressed trypsin(ogen) far less frequently (0% to 12%). The present
      results, taken together with those of previous studies, suggest that gelatinase A
      is associated with malignant behavior of all the types of lung tumors, whereas
      its activity may be controlled by the endogenous inhibitor TIMP-2. The aggressive
      clinical behavior of small cell carcinoma may be attributable, at least in part,
      to a loss of the inhibitory effect of TIMP-2, as a significant proportion of
      these tumors showed negative or low levels of TIMP-2 expression. Matrilysin and
      trypsin(ogen) expressions are unlikely to be correlated with the aggressiveness
      of lung tumors. The expression of trypsin (ogen) may rather reflect the
      differentiation of adenocarcinoma cells toward normal airway epithelial cells.

PMID- 9158712
TI  - Biopsy diagnosis of Creutzfeldt-Jakob disease by western blot: a case report.
AB  - Creutzfeldt-Jakob disease is a clinically and pathologically heterogeneous
      disorder that often requires brain biopsy for definitive diagnosis. We report the
      case of a 62-year-old man who underwent brain biopsy for progressive neurological
      deterioration. Histopathologically, there was minimal spongiform change that
      could not be unequivocally attributed to Creutzfeldt-Jakob disease. A 16 mg
      portion of gray matter saved frozen was subsequently analyzed by Western blot and
      showed definitive protease-resistant prion protein. This case illustrates
      applicability, ease in interpretation, and accuracy of Western blot analysis for
      protease-resistant prion protein in small brain biopsy specimens. Given the
      importance of accurate diagnosis in suspected prion disease, we recommend that a
      small portion of tissue from any brain biopsy performed in this setting be kept
      frozen for possible biochemical studies.

PMID- 9158713
TI  - Identical, unique p53 mutations in a primary ovarian mucinous adenocarcinoma and
      a synchronous contralateral ovarian mucinous tumor of low malignant potential
      suggest a common clonal origin.
AB  - The origin of malignant ovarian epithelial tumors is uncertain and has been the
      subject of considerably controversy. Some favor the theory of origin in precursor
      lesions such as benign cystadenomas or tumors of low malignant potential (LMP;
      borderline tumors), whereas others favor the concept of an independent origin of
      carcinomas from the ovarian surface epithelium or inclusion cysts. Recently, the
      demonstration of identical molecular alterations in morphologically benign and
      malignant areas within the same ovarian tumor have suggested the possibility that
      the malignant epithelium had undergone differentiation to a benign appearance.
      Because both areas were present in the same tumor, however, the possibility of
      progression of the morphologically benign component could not be excluded. We
      present a case of simultaneous mucinous carcinoma and contralateral tumor of LMP
      which exhibited identical, unique mutations of the p53 gene, suggesting a clonal
      origin. Because these were separate and distinct tumors, we believe this case
      provides strong support for the differentiation hypothesis. We also provide
      evidence for markedly different levels of p53 expression in areas with identical
      p53 mutations.

PMID- 9158714
TI  - Epithelial-myoepithelial carcinoma of the lung: immunohistochemical and
      ultrastructural observations and review of the literature.
AB  - Epithelial-myoepithelial carcinoma is a rare low-grade malignant salivary gland
      neoplasm that most commonly occurs in the parotid gland but can also arise in
      minor salivary glands. We report a case of a primary epithelial-myoepithelial
      carcinoma of the lung. The patient is a 55-year-old black woman who presented
      with increasing shortness of breath and productive cough of at least 3 months
      duration. A left lower lobe endobronchial lesion was identified radiographically.
      Surgical resection of the lesion was performed, obtaining a circumscribed,
      nonencapsulated 3.9 cm tan mass which was attached to the inner wall of the
      lateral basal segment bronchus. A biphasic proliferation of epithelial
      (cytokeratin positive; S-100 protein and muscle-specific actin negative) and
      myoepithelial (S-100 protein and muscle-specific actin positive with focal weak
      cytokeratin positive) cells was identified by immunohistochemical and
      ultrastructural analysis of formalin-fixed tissue. The patient is disease free 7
      months after resection. Pulmonary epithelial-myoepithelial carcinoma likely
      derives from the submucosal bronchial glands and should be added to the growing
      list of salivary gland-type neoplasms that may occur as primary pulmonary
      neoplasms. Because its histology is identical to salivary epithelial
      myoepithelial carcinoma, pulmonary epithelial-myoepithelial carcinoma should be
      considered a low-grade malignant neoplasm and should be designated as epithelial
      myoepithelial carcinoma is preference to other terms that may not convey its
      malignant potential. Although follow-up on reported cases is limited, lobectomy
      with negative bronchial margin should be curative.

PMID- 9158715
TI  - Staining for Helicobacter pylori: an E-mail survey.

PMID- 9158716
TI  - Periplasm, periplasmic spaces, and their relation to bacterial wall structure:
      novel secretion of selected periplasmic proteins from Pseudomonas aeruginosa.
AB  - A brief overview of thin sections of cryopreserved walls from select eubacteria
      will be presented to suggest that all bacteria have functional periplasms, but
      that these are not necessarily confined to a periplasmic space such as found in
      typical gram-negative bacteria. Pseudomonas aeruginosa contains many components
      in its periplasmic space, some of which are required for infection. Throughout
      its growth cycle, P. aeruginosa blebs-off membrane vesicles that can possess DNA,
      endotoxin, phospholipase, protease, hemolysin, alkaline phosphatase, and
      autolysin, each of which must have a molecular phase that resides in the
      periplasm. These membrane packets make good delivery systems to convey these
      components to other bacteria and, possibly, tissue. Aminoglycoside antibiotics,
      such as gentamicin, produce a serious perturbation on the bacterium's surface
      (separate from the ribosomal effect), which contributes to the killing of the
      microorganism. Antibiotics such as this increase the size and number of the
      membrane blebs, which could contribute to septic shock of patients under drug
      therapy.

PMID- 9158717
TI  - Overall protein content and induced enzyme components of the periplasm of
      Bacillus subtilis.
AB  - Estimates for the overall protein content of the periplasm of Escherichia coli
      range from 4 to 16% of cellular protein. A cursory examination of known sources
      of contamination inherent to the methods employed for measurement leads to the
      conclusion that even the lower value may represent an overestimate of the
      periplasmic protein in E. coli. The protoplast supernatant fraction (PSF) of
      Bacillus subtilis defines operationally a potential periplasm, which, after
      correction for cytoplasmic contamination, yielded, in B. subtilis strains 168 and
      W23, calculated values of 9 and 3%, respectively, of cell protein as being
      periplasmic. 26 Among enzymes typically periplasmic in E. coli, at least two,
      RNases and a 5'-nucleotidase, were located in the B. subtilis periplasm. Compared
      to other cell fractions, RNase activity in the periplasm was associated with
      several protein bands forming a unique profile. Samples from all growth phases of
      cells cultured under phosphate-limitation and phosphate-excess revealed that a
      major part of both investigated activities was induced by phosphate depletion and
      located outside the plasma membrane. The current belief that a periplasm
      containing soluble enzymes does not exist in gram-positive bacteria is examined
      in light of the absence of an outer membrane permeability barrier, and of a
      clearly defined electron-transparent zone located between the plasma membrane and
      the cell wall of B. subtilis. Previous results of studies of protein secretion,
      and cell wall permeability, are reinterpreted by assuming that the thick charged
      cell wall of gram-positive bacteria can act as the outer permeability barrier,
      and as such be the functional equivalent of the outer membrane of gram-negative
      organisms.

PMID- 9158718
TI  - Are S-layer glycoproteins and lipopolysaccharides related?
AB  - Several glycan structures of S-layer glycoproteins of gram-positive eubacteria
      were compared with the principal structural organization of O-antigens of
      lipopolysaccharides of gram-negative eubacteria. Further, activated intermediates
      of the biosynthetic pathway of S-layer glycans were compared with activated
      intermediates of the route of assembly of lipopolysaccharide O-antigens. As a
      result, at least structural similarities between both types of molecules have
      been clearly observed. More detailed studies of the assembly of S-layer glycans
      are required to unambiguously demonstrate the extent to which the biosynthetic
      pathways of both molecules are related.

PMID- 9158719
TI  - Study of the overproduced uridine-diphosphate-N-acetylmuramate:L-alanine ligase
      from Escherichia coli.
AB  - The UDP-N-acetylmuramate:L-alanine ligase of Escherichia coli is responsible for
      the addition of the first amino acid of the peptide moiety in the assembly of the
      monomer unit of peptidoglycan. It catalyzes the formation of the amide bond
      between UDP-N-acetylmuramic acid (UDP-MurNAc) and L-alanine. The UDP-MurNAc-L
      alanine ligase was overproduced 2000-fold in a strain harboring a recombinant
      plasmid (pAM1005) with the murC gene under the control of the inducible promoter
      trc. The murC gene product appears as a 50-kDa protein accounting for ca. 50% of
      total cell proteins. A two-step purification led to 1 g of a homogeneous protein
      from an 8-liter culture. The N-terminal sequence of the purified protein
      correlated with the nucleotide sequence of the gene. The stability of the
      enzymatic activity is strictly dependent on the presence of 2-mercaptoethanol.
      The K(m) values for substrates UDP-N-acetylmuramic acid, L-alanine, and ATP were
      estimated; 100, 20, and 450 microM, respectively. The specificity of the enzyme
      for its substrates was investigated with various analogues. Preliminary
      experiments attempting to elucidate the enzymatic mechanism were consistent with
      the formation of an acylphosphate intermediate.

PMID- 9158720
TI  - Staphylococcal peptidoglycan interpeptide bridge biosynthesis: a novel
      antistaphylococcal target?
AB  - In staphylococci, crosslinking of the peptide moiety of peptidoglycan is mediated
      via an additional spacer, the interpeptide bridge, consisting of five glycine
      residues. The femAB operon, coding for two approximately 50-kDa proteins is known
      to be involved in pentaglycine bridge formation. Using chemical mutagenesis of
      the beta-lactam-resistant strain BB270 and genetic, biochemical, and biophysical
      characterization of mutants selected for loss of beta-lactam resistance and
      reduced lysostaphin sensitivity it is shown that peptide bridge formation
      proceeds via three intermediate bridge lengths (cell wall peptides with no, one,
      three, and five glycine units). To proceed from one intermediate to the next,
      three genes appear necessary: femX, femA, and femB. The drastic loss of beta
      lactam resistance after inactivation of FemA or partial impairment of FemX even
      beyond the level of the sensitive wild-type strains renders these proteins
      attractive antistaphylococcal targets.

PMID- 9158721
TI  - Regulation of the glutamate racemase of Escherichia coli investigated by site
      directed mutagenesis.
AB  - The biosynthesis of D-glutamic acid, one of the essential components of bacterial
      cell-wall peptidoglycan, is catalyzed by a glutamate racemase in Escherichia
      coli. While the other reported glutamate racemases from various (essentially gram
      positive) bacterial species did not require any specific activator, the E. coli
      enzyme absolutely requires the presence of the peptidoglycan precursor UDP-N
      acetylmuramyl-L-alanine to catalyze the interconversion of glutamic acid isomers.
      A comparison of the amino acid sequences of these different enzymes was made to
      identify amino acid residues from the E. coli enzyme that are involved in the
      catalysis or binding to the activator. Site-directed mutagenesis experiments are
      described that demonstrate the participation of cysteines 96 and 208 in the two
      base reaction mechanism of the enzyme. The construction of N- or C-terminal
      truncated enzymes is also described. The attractive hypothesis that the
      characteristic N-terminal amino acid extension (20 residues) of the E. coli
      enzyme could be involved in its activation by the nucleotide precursor is
      disproved by these experiments.

PMID- 9158722
TI  - Study of the reaction mechanism of the D-glutamic acid-adding enzyme from
      Escherichia coli.
AB  - The D-glutamic acid-adding enzyme of Escherichia coli, or MurD, was purified from
      an overproducing strain and a few aspects of its reaction mechanism were studied.
      The existence of a reactive cysteinyl residue was shown by the following
      experiments: (1) two thiol-modifying reagents, (5,5'-dithiobis)2-nitrobenzoic
      acid and 2-nitro-5-thiocyanobenzoic acid, inactivated the enzyme; (2) incubation
      with tetranitromethane led to inactivation and to the appearance of cysteic acid
      (not to 3-nitrotyrosine); (3) in each case, ATP or UDP-MurNAc-L-Ala (but not D
      glutamic acid) protected the enzyme from inactivation. The existence of a
      reactive lysyl residue was shown by the action of 2,4,6-trinitrobenzenesulfonic
      acid, a reagent specific for lysyl residues present in phosphate-binding sites.
      The formation of an acyl phosphate intermediate was consistent with three types
      of results: (1) the molecular isotope exchange reaction, which took place only in
      the presence of phosphate, but which was not strictly dependent on the presence
      of ADP; (2) a release of phosphate, measured by the molybdate assay, observed
      when the enzyme was incubated with ATP and UDP-MurNAc-L-Ala (without D-glutamic
      acid); (3) the appearance of a new radioactive compound (besides ATP and Pi)
      after incubation for a few minutes with UDP-MurNAc-L-Ala and [gamma-32P]ATP.
      Finally, the fact that phosphinate 1 was a good inhibitor of the enzyme (IC50 =
      0.7 microM) strongly suggested that a tetrahedral transition state follows the
      acyl phosphate in the reaction pathway.

PMID- 9158723
TI  - How does FtsZ find its location?
AB  - The conformational flexibility of FtsZ and the properties of its epitopes have
      been studied. Cellular fractions of Escherichia coli have been treated with
      Triton X-114. FtsZ distributed in the polar as well as in the non-polar phase.
      This has been interpreted to mean that FtsZ can change its conformation. For the
      nonpolar conformation it has been assumed that the putative hydrophobic pocket of
      FtsZ (cf. Voskuil et al., J. Bacteriol. 176:1886-1893) is being turned inside out
      upon interaction with the cytoplasmic membrane. In a tentative model we suggest
      that FtsA mediates this interaction. Immunoprecipitations of FtsZ with various
      monoclonal antibodies in the presence or absence of 1 M NaCl gave a clue
      concerning the hydrophobicity and hydrophilicity of FtsZ's epitopes. Immunogold
      labeling also showed differences with respect to the accessibility of FtsZ.

PMID- 9158724
TI  - Overproduction of penicillin-binding protein 7 suppresses thermosensitive growth
      defect at low osmolarity due to an spr mutation of Escherichia coli.
AB  - Escherichia coli delta prc mutants lacking periplasmic protease Prc, which was
      originally found involved in the C-terminal processing of penicillin-binding
      protein (PBP) 3, show thermosensitive growth at low osmolarity. We isolated
      thermoresistant revertants containing extragenic suppressor (spr) mutations. In
      the prc+ background the mutations also caused thermosensitivity at low
      osmolarity. They were all mapped at about 48 min on the chromosome and most
      probably allelic to one another. From this chromosomal region we cloned a gene
      that could correct the thermosensitive defect of an spr mutant, which turned out
      to be a multicopy suppressor of spr. Analysis of the nucleotide sequence
      predicted that the gene would code for a low-molecular-weight PBP, and penicillin
      binding experiments revealed the product to be PBP 7. Disruption of the gene on
      the chromosome caused no apparent growth defect. PBP 7 seemed to be degraded by
      protease Prc. Overproduction of mutant PBP 7 that had the active site serine
      residue replaced with alanine did not correct the spr thermosensitivity,
      suggesting importance of the DD-endopeptidase activity in the multicopy
      suppression.

PMID- 9158725
TI  - Purification and light-scattering analysis of penicillin-binding protein 4 from
      Escherichia coli.
AB  - Penicillin binding protein 4 (PBP4) from Escherichia coli is a protein involved
      in the recycling and maturation of the bacterial cell wall and it is inhibited by
      beta-lactam antibiotics. PBP4 exhibits D-Ala-D-Ala-endopeptidase as well as D-Ala
      D-Ala-carboxypeptidase activity. To provide a structural template for the design
      of new, more specific antibiotics we started X-ray crystallographic studies of
      penicillin binding protein 4 from Escherichia coli. PBP4 has been overexpressed
      in Escherichia coli as a His-tagged protein. A large-sclae purification scheme,
      yielding a very pure material, has been set up and crystallization experiments
      have been started. Dynamic light scattering experiments suggested that PBP4
      exhibits aggregation behavior with a number of different precipitating agents and
      additives. Only by addition of EDTA, PEG 4000, and ammonium sulfate is the
      molecular mass about 110 kDa.

PMID- 9158726
TI  - The dlt operon in the biosynthesis of D-alanyl-lipoteichoic acid in Lactobacillus
      casei.
AB  - The D-alanine incorporation system allows Lactobacillus casei to modulate the
      chemical properties of lipoteichoic acid (LTA) and hence control its proposed
      functions, i.e., regulation of autolysin action, metal ion binding, and the
      electromechanical properties of the cell wall. The system requires the D-alanine
      D-alanyl carrier protein ligase (Dcl) and the D-alanyl carrier protein (Dcp). Our
      results indicate that the genes for these proteins are encoded in the dlt operon
      and that this operon contains at least 2 other genes, dltB and dltD. The aim of
      this paper is to describe the genetic organization of the operon, the role of the
      D-alanyl carrier protein, and the function of the putative protein encoded by
      dltB in the intramembranal translocation of the activated D-alanine.

PMID- 9158727
TI  - Lipoteichoic acid as a target for antimicrobial action.
AB  - Daptomycin, a lipopeptide antibiotic active against gram-positive bacteria, has
      been found to inhibit lipoteichoic acid (LTA) synthesis as a consequence of
      membrane binding in the presence of Ca2+. The present study shows that among the
      bacterial-membrane components, daptomycin binds the protein fraction with a
      noncovalent bond, as suggested by the instability of the bond in the presence of
      an ionic detergent such as sodium dodecyl sulfate. Analysis of membrane proteins
      by isoelectric focusing electrophoresis reveals that 5 bands with isoelectric
      points ranging from 5.9 to 6.2 bind radioactive daptomycin. These proteins are
      therefore called daptomycin-binding proteins. In an attempt to correlate these
      proteins with the main inhibition observed in LTA synthesis, two-dimensional thin
      layer chromatography of lipids synthesized during daptomycin treatment was
      performed. A 3-fold increase in diglucosyl diacylglycerol is demonstrated, while
      the compounds phosphatidyl-alpha-kojibiosyldiacylglycerol,
      glycerophosphophosphatidyl-alpha-kojibiosyldiacyl glycerol, and
      glycerophosphokojibiosyldiacylglycerol, which follow diglucosyl diacylglycerol in
      LTA synthesis, decrease progressively with time during the course of daptomycin
      treatment.

PMID- 9158728
TI  - Cellular signals regulating antibiotic sensitivities of bacteria.
AB  - The effects of bacterial masses upon the drug resistance of neighboring bacteria
      were investigated. The experiments were performed with plastic Petri dishes
      divided into two identical compartments. A growing mass of Bacillus subtilis
      (signal emitter cell) in one compartment exerted enhancing effects upon the
      erythromycin and streptomycin resistance of Bacillus carboniphilus (signal
      recipient) cells, sparsely seeded in the other compartment, through the plastic
      wall and the air. These effects of the growing mass of cells are attributed to
      the emission of "sonic" signals.

PMID- 9158729
TI  - Bacterial walls, peptidoglycan hydrolases, autolysins, and autolysis.
AB  - Knowledge of the chemistry, ultrastructure, biosynthesis, assembly, and function
      of bacterial cell walls has expanded enormously since the opening of this field
      of research approximately 40 years ago, primarily by the early work of Milton
      Salton. It has become abundantly clear that, in most environments, walls are
      essential to the survival and growth of bacteria and in many ways are
      structurally and functionally unique. A common but not universal feature of
      bacterial walls is the presence of peptidoglycan (PG; murein, or in the case of
      certain Archae the analogous structure-pseudomurein). PGs are considered to be
      primarily responsible for the protective and shape-maintaining properties of
      walls. They are a biologically unique class of macro-molecules in that they are
      not linear or even branched macromolecules. Instead they are two- or three
      dimensional net like polymers that are linked together by three different
      chemical bonds (glycosidic, amide, and peptide). In addition, they contain the D
      isomers of some amino acids and therefore may possess DL, LD, and DD linkages.
      Furthermore, the exact chemical structure of a PG may vary depending on
      environmental factors, however, retaining the essential protective and shape
      maintaining properties of the wall. Thus, the overall architectural plan of the
      wall may be more important than the exact shape of the bricks used for the
      construct. Another somewhat unique feature of PGs (and walls) is their final
      assembly in situ on the outside of the cellular permeability barrier. A broad
      variety of bacteria have been shown to possess enzymes that can hydrolyze bonds
      in the wall PG. Hydrolysis of a sufficient number of bonds can result in the
      weakening of, or serious damage to, the protective properties of the PG.
      Frequently, a bacterial strain may possess more than one PG hydrolase activity. A
      commonly believed, but as yet unproven, hypothesis is that PG hydrolases play one
      or more roles in PG assembly and/or surface growth and cell division. At a
      minimum, such potentially suicidal activities must be exquisitely well regulated.
      Currently we know little concerning the regulation of these activities, or how
      they communicate with, and integrate with, chromosome replication, synthesis of
      cytoplasmic macromolecules, cell growth, and division, although such, probably
      two-way, communications must occur in growing and dividing cells. Recent data
      indicate that the psr element in Enterococcus hirae described by Fontana and
      collaborators as a genetic element that is involved in the regulation of the
      synthesis of PBP 5, also is involved in the regulation of several other surface
      properties. These properties include (1) autolysis rates of exponential phase.
      cells, (2) the retention of this property after cells enter the stationary phase,
      (3) lysozyme sensitivity, and (4) the ratio of rhamnose-containing wall
      polysaccharide to PG in the walls. Thus the psr element may be a part of a
      "global" regulation and communication system in E. hirae.

PMID- 9158730
TI  - Molecular interplay of murein synthases and murein hydrolases in Escherichia
      coli.
AB  - Affinity chromatography using different lytic transglycosylases as a specific
      ligand revealed an interaction of both murein hydrolases and murein synthases.
      This interaction is taken as evidence for the assemblage into a multienzyme
      complex that could function as a murein replicase precisely copying the given
      three-dimensional structure of the murein sacculus. The sacculus of the mother
      cell would function as a template, which is identically replicated by copying the
      lengths of the existing glycan strands and the pattern of crosslinkages. A
      hypothetical enzyme complex specifically involved in cell division and a complex
      specifically involved in cell elongation are presented. It is postulated that
      PBPs 1a and/or 1b are present in both complexes, whereas the presence of PBP2 or
      PBP3 defines the specificity of the murein-synthesizing machinery as being
      involved in either cell elongation or septation. Moreover, the proposed
      "holoenzyme" suprastructure could explain why the specific inhibition of PBPs
      1a/1b results in bacteriolysis and why inhibition of PBP2 and PBP3 causes the
      well-known morphological alterations, spherical growth, and filamentation,
      respectively.

PMID- 9158731
TI  - The convergence of murein recycling research with beta-lactamase research.
AB  - The story of how investigation of Escherichia coli cell wall elongation evolved
      into a study of murein recycling and how this led to the discovery that ampG and
      ampD were required for both murein recycling and beta-lactamase regulation is
      chronicled. Preliminary information on two other genes believed to be involved in
      recycling, nagZ, the structural gene for beta-N-acetylglucosaminidase, and tpl,
      the presumed structural gene for the hypothetical tripeptide-adding enzyme, is
      presented. The possibility that recycling of murein fragments serves a signaling
      function is discussed.

PMID- 9158732
TI  - Peptidoglycan hydrolases of Bacillus subtilis 168.
AB  - There are multiple peptidoglycan hydrolases associated with Bacillus subtilis 168
      and these potentially lethal enzymes have been implicated in a number of
      important cellular processes. Several enzymes have been studied at the molecular
      level and their structural genes characterized. This information has begun to
      identify roles for individual enzymes in motility, cell separation,
      differentiation, and phage lysis. It has become apparent that in many cases
      important autolytic functions can be performed by more than one enzyme, so the
      complex web of mutually compensatory components can be unraveled only by making
      multiple mutants. One such multiple mutant has revealed the presence of several
      previously unknown minor autolysins, the functions of which are currently
      obscure.

PMID- 9158733
TI  - Effect of the SinR protein on the expression of the Bacillus subtilis 168 lytABC
      operon.
AB  - Transcription of the lytABC operon was determined by extension of primers on RNAs
      isolated from strains bearing a deficient sinR gene. A SinR null mutant, in which
      part of the sinR gene was deleted, exhibits a pattern identical to that
      characteristic of FlaB (SigD) deficient mutants, i.e., loss of the signal
      corresponding to the SigD-dependent promoter, but not of that recognized by the
      SigA form of the RNA polymerase. However, strains bearing either flaD1 or flaD2,
      two different point mutations of gene sinR, were characterized by a complete loss
      of signals corresponding to both promoters. Thus, modified FlaD1 and FlaD2
      proteins behave like a repressor affecting the expression of lytABC more severely
      than does the absence of SinR, The most obvious interpretation of this
      observation is a direct interaction between the SinR protein and the promoters
      recognized by the SigD form of the RNA polymerase.

PMID- 9158734
TI  - D-alanine deprivation of Bacillus subtilis teichoic acids is without effect on
      cell growth and morphology but affects the autolytic activity.
AB  - Using insertional inactivation of the different genes of the dlt operon in
      Bacillus subtilis, we searched for metabolic and morphological changes caused by
      D-alanine ester deprivation of lipoteichoic acid and wall teichoic acid. There
      were no alterations of cell growth, basic metabolism, cellular content of
      phosphorus-containing compounds, ultrastructure, cell separation, and surface
      charge. The only alteration observed was an enhancement of endogenous and beta
      lactam-induced cell lysis. Since this enhancement is doubtless correlated with
      the D-alanine ester deprivation of the teichoic acids, the present view based on
      in vitro experiments, that negatively charged LTA is inhibitory to autolysins,
      may be questioned. We propose that negatively charged lipoteichoic acid and/or
      wall teichoic acid serve in vivo to fix the cationic autolysins within the cell
      wall-membrane complex by electrostatic interaction. Positively charged D-alanine
      ester substituents decrease the binding capacity of the teichoic acids for
      autolysins by charge compensation.

PMID- 9158735
TI  - Inhibition of peptidoglycan hydrolase activity in vivo and in vitro by energy
      uncouplers in Escherichia coli.
AB  - The effects of energy uncouplers on in vivo and in vitro peptidoglycan hydrolase
      activities in Escherichia coli were determined. Sodium azide, potassium cyanide,
      and carbonyl cyanide m-chlorophenylhydrazone all inhibited ampicillin-induced
      lysis of exponential phase cultures, even when they were added to lysis-committed
      cultures. These energy uncouplers also inhibited the solubilization of
      radiolabeled peptidoglycan by bacterial suspensions that had been treated with 5%
      trichloroacetic acid by the method of Hartmann et al.3 to activate the
      peptidoglycan hydrolases. Therefore, the in vivo and in vitro activities of
      peptidoglycan hydrolases in E. coli are dependent on membrane energization.

PMID- 9158736
TI  - The role of O-acetylation in the metabolism of peptidoglycan in Providencia
      stuartii.
AB  - The gentamicin 2'-N-acetyltransferase [EC 2.3.1.59; AAC(2')-Ia] of Providencia
      stuartii was shown to contribute to the O-acetylation of peptidoglycan and
      mutants that either under- or overexpress the aac(2')-Ia gene was characterized
      phenotypically to possess either lower or higher levels of peptidoglycan O
      acetylation, respectively, compared to the wild-type. These mutants were
      subjected to scanning electron microscopy. P. stuartii PR100, with 42-44%
      peptidoglycan O-acetylation compared to 54% for the wild-type, appeared as
      irregular rods. In direct contrast, strains PR50.LM3 and PR51, with increased
      levels of peptidoglycan O-acetylation (63 and 65%, respectively), appeared as
      coccobacilli or chain formers, respectively. Zymogram analysis of the autolysins
      produced by another member of the closely related Proteeae group of bacteria,
      Proteus mirabilis, indicated the presence of three classes of enzymes: one that
      acts preferentially on native, O-acetylated peptidoglycan, a second that
      hydrolyses non-O-acetylated peptidoglycan, and a third that is not distinguished
      by the two forms of substrate. On the basis of the apparent morphological changes
      directly related to levels of O-acetylation combined with the presence of
      different classes of autolysins, a model is proposed that invokes the role of
      this modification in the control of autolysins for the maintenance of the
      structure of the peptidoglycan sacculus.

PMID- 9158737
TI  - Identification of new members of the lytic transglycosylase family in Haemophilus
      influenzae and Escherichia coli.
AB  - Although bacterial peptidoglycan metabolism and numerous of the enzymes involved
      therein have been studied extensively over the years, information on the precise
      number of these enzymes is still lacking as is knowledge on the specific function
      of most of them. This observation holds true even for the well-studied bacterium
      Escherichia coli. Through determination of the complete sequences of bacterial
      genomes, that of Haemophilus influenzae being the first example, the opportunity
      arises to obtain a comprehensive overview of the members of the different
      families of peptidoglycan metabolizing enzymes by identification of their genes.
      Following this rationale, H. influenzae and E. coli genomic sequence was searched
      for new members of the family of lytic transglycosylases, using three-dimensional
      structure-derived sequence information. A new putative lytic transglycosylase
      gene could be identified in both bacterial species. The gene from E. coli was
      cloned and peptidoglycan hydrolase activity was demonstrated for the gene
      product.

PMID- 9158738
TI  - Bacteriophage lambda lysis gene product modified and inserted into Escherichia
      coli outer membrane: Rz1 lipoprotein.
AB  - Lysis proteins of bacteriophage lambda were localized in different parts of the
      host envelope: S in the inner membrane,36 Rz in the membrane adhesion sites,14
      and Rz1 in the outer membrane. The R gene product, the transglycosylase
      destroying bacterial murein, is a soluble protein. Computer-assisted analysis of
      the Rz1 protein amino acids sequence revealed that its N-terminal part contained
      the site 15VVVG [symbol: see text] C20, which could be recognizable for the SPase
      II and cleaved leaving lipid modified C20 as the N-terminal amino acid of the
      mature protein. Microsequencing of the Rz1 protein isolated from the expression
      products of E. coli [pSB54] carrying the Rz1 gene showed that the N-terminal part
      of the protein was cleaved as predicted. Lipid labeling with [3H]palmitate
      confirmed the expectation that Rz1 was a lipoprotein. E. coli [pSB54] treated
      with globomycin accumulated prolipoprotein, the Rz1 precursor, which was
      detectable by the anti-Rz1 serum on electropherograms as the 6.5-kDa protein,
      larger than mature protein. Physiological function of the Rz1 protein remains to
      be discovered, but as a first hint we noticed that it evokes increase of the
      fraction of adhesion sites of outer and inner membranes when overproduced from
      pSB54. The same effect was observed in induced E. coli (lambda) just before the
      lysis onset, however, one should be cautious in interpreting the results obtained
      in conditions of the overproduction of the Rz1 lipoprotein.

PMID- 9158739
TI  - Affinity chromatography as a means to study multienzyme complexes involved in
      murein synthesis.
AB  - The interaction of murein hydrolases and synthases was studied by affinity
      chromatography. The lytic transglycosylases Slt70 and MltB of E. coli were
      purified and covalently linked to CNBr-activated Sepharose. Membrane extracts
      were analyzed for proteins that interact with the immobilized murein hydrolases.
      Slt70-Sepharose was found to retain the PBPs 1b, 1c, 2, and 3. Likewise MltB
      Sepharose enriched PBP 1b, 1c, and 3. Thus both lytic transglycosylases have an
      affinity for a transpeptidase, PBP2 and/or 3, as well as for the bifunctional
      transpeptidase/transglycosylase 1b. Interestingly, in addition, the poorly
      characterized PBP 1c interacts strongly with both Slt70 and MltB. It is
      speculated that the lytic transglycosylases assemble a multienzyme complex
      consisting of hydrolases and synthases, which is involved in growth of the stress
      bearing murein sacculus.

PMID- 9158740
TI  - Penicillin resistance and autolysis in enterococci.
AB  - Comparison of several cell wall-related properties of the ATCC 9790 strain and
      the R40 strain, a penicillin-resistant, PBP5 overproducing strain, and Rev14, a
      penicillin-hypersensitive, PBP5-deficient strain, is consistent with a role of
      the genetic element, psr, in the global regulation of lysozyme sensitivity,
      autolytic capacity, and wall-rhamnose-containing polysaccharide content. These
      parameters appear to be independently regulated by a system that involves psr in
      a currently unknown manner.

PMID- 9158741
TI  - Beta-Lactam antibiotic resistance in gram-positive bacterial pathogens of the
      upper respiratory tract: a brief overview of mechanisms.
AB  - Streptococcus pneumoniae and Group A Streptococci are frequent colonizers and
      major causative agents of disease in the upper respiratory tract of humans. In
      spite of the immense and common selective pressure of beta-lactam antibiotics
      against both of these bacterial species during the last four to five decades,
      penicillin-resistant strains of group A streptococci have not been described in
      the clinical literature as of 1994. This is particularly puzzling since
      penicillin-resistant mutants of this bacterium have been isolated repeatedly in
      the laboratory and such mutants carry altered penicillin-binding proteins (PBPs)
      with reduced drug affinities, i.e., a basic mechanism identical to the one seen
      in penicillin-resistant isolates of Streptococcus pneumoniae that have emerged in
      large numbers and at numerous locations and have spread explosively all over the
      globe by the beginning of the 1990s. The reasons for this contrasting situation
      are not clear. In Streptococcus pneumoniae the resistance mechanism to penicillin
      appears to originate in recombinational events between ancestral pneumococcal
      cells and as yet unidentified extra species DNA donors and probably involves the
      process of genetic transformation for which this bacterium has a remarkable
      hormonally controlled mechanism. The integration of foreign DNA sequences in the
      pneumococcal PBP genes leads to the remodeling of at least four of the five PBPs
      that change in their kinetic properties and increase in the penicillin resistance
      level of the bacteria also seems to involve increased production of the low
      affinity binding proteins.

PMID- 9158742
TI  - beta-Lactamase induction in gram-negative bacteria is intimately linked to
      peptidoglycan recycling.
AB  - A number of Gram-negative organisms normally express a chromosomally mediated
      class C beta-lactamase that is inducible by beta-lactam antibiotics. Data have
      recently emerged suggesting a close link between beta-lactamase induction and the
      recycling of released muramyl peptides from the bacterial peptidoglycan. Thus the
      AmpG transporter is responsible for the uptake into the cell of GlcNAc-anhMurNAc
      tripeptide. A mutant unable to express AmpG is therefore unable to recycle the
      cell wall and is at the same time not possible to induce by a beta-lactam. Once
      inside the cytosol the above muramyl peptide and its derivative anhMurNAc
      tripeptide is degraded by the cytosolic AmpD amidase that specifically releases
      the tripeptide from cytosolic muramyl peptides brought into the cell via AmpG.
      Mutants unable to produce AmpD are blocked in a cytosolic step for cell wall
      recycling and accumulate large amounts of cytosolic anhMurNAc-tripeptide. It is
      believed that cytosolic muramyl peptides can act as ligands for the beta
      lactamase regulator AmpR to activate expression of beta-lactamase. AmpD mutants,
      therefore, constitutively overproduce the chromosomal beta-lactamase and are beta
      lactam resistant. In wild-type strains beta-lactams that result in an increased
      cell wall breakdown will cause an increase in the cytosol of muramyl peptides
      leading to beta-lactamase induction. Mutants affected in the ampD gene arise
      readily during treatment with third-generation cephalosporins. Since these
      mutants lack a functional cell wall recycling system they may be at a
      disadvantage in the absence of selection. However, since muramyl peptides may act
      as cytotoxins, especially for respiratory epithelial cells, ampD mutants due to
      their large accumulation of anhMurNAc-tripeptide may be altered in their
      pathogenic properties as compared to wild-type cells possessing a normal cell
      wall recycling system.

PMID- 9158743
TI  - Pneumococcal resistance to beta-lactam antibiotics: a global geographic overview.
AB  - beta-Lactam resistance in Streptococcus pneumoniae has spread over the entire
      world. The 10 main foci of resistant organisms are located in the following
      areas: (1) southwest Europe (Spain, France, Portugal), (2) central-east Europe
      (Hungary, Roumania, Bulgaria, Turkey) and Israel, (3) northwest Russia, (4) South
      Africa, (5) Japan and South Korea, (6) Papua-New Guinea, (7) Alaska, (8)
      southeast North America, (9) southwest North America, and (10) south cone in
      South America. A comparison of the presumed factors influencing the increase of
      pneumococcal resistance in these foci with those occurring in low incidence
      areas, such as central-north Europe, Scandinavia, north and western Africa, or
      middle-north Mediterranean countries (Italy, Greece) should provide the clues to
      predict and prevent further spread of resistant pneumococci.

PMID- 9158744
TI  - Epidemiology of penicillin resistant pneumococci in Iceland.
AB  - The prevalence of penicillin-resistant pneumococci (PRP) has been increasing,
      with the highest levels reported from countries with relatively unrestricted
      antimicrobial use. It has been low in northern Europe except Iceland, which is
      disconcerting as antimicrobial use in Iceland has been relatively restricted.
      This suggests that other factors may facilitate their spread. By studying their
      epidemiology and possible risk factors for carriage, we have attempted to explain
      their rapid spread in Iceland. The incidence of infections caused by PRP (as
      percentage of infections considered due to pneumococci) has increased from 0% in
      1988 to 2.3% in 1989, 2.7% in 1990, 8.4% in 1991, 16.3% in 1992, and 19.8% in
      1993. The infections have mainly affected 0- to 3-year-old children (71.4%), and
      the PRP belonged almost exclusively to serogroups 6, 19, and 23 (98.8%). Most
      were serotype 6B multiresistant (75%; resistant to penicillin (MIC = 1.0),
      cephalothin, erythromycin, clindamycin, tetracycline, chloramphenicol, fusidic
      acid, sulfonamides, and trimethoprim), and believed to belong to a single clone
      originating from Spain. The PRP have been prevalent in healthy children, 0-10%
      nasopharyngeal carriage, especially in day-care centers, with the highest
      prevalence in areas that had the highest antimicrobial consumption. Recent
      antimicrobial consumption, especially of trimethoprim-sulfa, appeared to increase
      PRP carriage. The rapid spread of PRP in Iceland may have been facilitated by
      high antimicrobial consumption in day-care centers (especially of trimethoprim
      sulfa) which are attended by the majority of Icelandic children.

PMID- 9158745
TI  - Epidemiology of resistant pneumococci in Hungary.
AB  - Data on resistance in Streptococcus pneumoniae was analyzed in cohorts of
      isolates from nasal carriers without respiratory tract infection, nose-throat
      swabs, and ear fluid specimens of children, from sputum and bronchoalveolar
      lavage of adults and central spinal fluid, blood, and pleural fluid of patients
      without a distinction of age group. Colonizing strains in infant carriers showed
      a higher resistance rate (47.5%) to penicillin than in other children (24.2%).
      Isolates of inpatients, predominantly infants with respiratory tract infection,
      presented a higher prevalence of resistance than outpatients in all age groups.
      Adults showed the lowest resistance rates. Resistance was rarer among S.
      pneumoniae isolates from patients with systemic infection. The few cases caused
      by resistant S. pneumoniae should raise concern. Resistance among strains from
      ear fluid was more prevalent in all investigated population groups than among
      isolates from throat-nose swabs. The similarity of resistance rates to
      erythromycin and penicillin was associated with frequent combined resistance.
      While the prevalent serotype among the resistant strains was 19A, no predominant
      serotype was found among the susceptible strains.

PMID- 9158746
TI  - Epidemiology of antibiotic resistance in Haemophilus influenzae.
AB  - During the last 10 years, a continuous increase in the incidence of beta
      lactamase-producing Haemophilus influenzae has been observed; in addition, beta
      lactamase-negative ampicillin-resistant strains are better identified and more
      frequently isolated. During the same period, resistance to tetracyclines and
      chloramphenicol decreased to a very low level. The incidence of resistant
      bacteria is highly variable according to the site of infection, patient's age,
      type of Haemophilus, and country or region, according to local epidemiological
      factors. Follow-up multicenter studies are needed to monitor the evolution of
      resistance to these antibiotics and also emergence and spread of resistance to
      other antibiotics, such as new fluoroquinolones, new beta-lactams, and new
      macrolides.

PMID- 9158747
TI  - Epidemiologic aspects on antibiotic resistance.
AB  - The increasing usage of antibiotics has selected for resistant bacteria. Spread
      of such bacteria may follow mathematical models of infectious diseases, taking
      into consideration the number of infectious individuals, the number of
      susceptible individuals, and the effective contact rate between individuals from
      these two groups. According to calculations of the theoretical epidemic curves,
      the highest incidence of individuals infected with a resistant bacterial strain
      is present when the prevalence of patients and carriers is approximately 20-80%.
      Moreover, the rapidity of the spread of an epidemic increases drastically if the
      total number of individuals in the exposed group increases and also if the
      contact rate increases. This means that precautions to stop an epidemic spread of
      a resistant bacterial strain in a given group of individuals should be undertaken
      early when the prevalence is below 20%. Efficient precautions consist of cohort
      isolation, decrease of the number of individuals in exposed groups by subdivision
      into several smaller groups, and decrease of contact rates by hygienic
      precautions. Examples are given where such precautions have proven efficient.

PMID- 9158748
TI  - Clinical aspects on antibiotic resistance: upper respiratory tract infections.
AB  - In view of the increased resistance to antibiotics in several upper airway
      pathogens, the clinical rationale for use of antimicrobial therapy in various
      upper respiratory tract infections is discussed. The diagnostic skill and the
      clinical significance of various bacteria are taken into account and strategies
      for treatment of the different infections, with focus on acute otitis media, are
      discussed.

PMID- 9158749
TI  - Pneumonia: the impact of antibiotic resistance on its management.
AB  - Pneumonia in the community affects between 1 and 5 per 1000 per year. The
      microbial aetiology is diverse and influenced by preexisting disease,
      seasonality, as well as animate and inanimate environmental sources; pneumococci,
      Legionella spp., Mycoplasma pneumoniae, and more recently Chlamydia pneumoniae
      are the predominant bacterial pathogens. Gram-negative enteric bacteria although
      less common are particularly virulent. Antibiotic resistance is well established
      for Haemophilus influenzae and Gram-negative bacillary infections, but has been a
      recent phenomenon in the case of Streptococcus pneumoniae, which is numerically
      the leading pathogen. Despite the concerns raised by this reduced susceptibility
      to penicillin, evidence that this has been translated into increased clinical
      failures is currently difficult to establish. Macrolide and tetracycline
      resistance among pneumococci is more common. beta-Lactamase production by H.
      influenzae has now reached levels where, in those with severe pneumonia, beta
      lactamase stable agents are preferred. Consensus Guidelines on the treatment of
      community acquired pneumonia have been published by the British Thoracic Society,
      the American Thoracic Society, and from Expert Panels in Canada and France. These
      emphasize severity assessment and differentiate management in the community or
      hospital setting. The recommended regimens are compared and contrasted. In
      conclusion, mild/moderate pneumonia, when pneumococcal in nature, is likely to
      still respond to amoxycillin or penicillin G, but in higher dosages where
      pneumococcal resistance is documented. However, in severe infection where
      pneumococcal resistance, other beta-lactamase-producing pathogens, or an atypical
      infection could be operating, it is important that initial empirical therapy be
      broad spectrum and promptly administered. Treating multiresistant pneumococcal
      disease in those allergic to beta-lactams presents a particular dilemma.
      Glycopeptides are currently preferred.

PMID- 9158750
TI  - Acute and chronic bronchitis.
AB  - Although questions persist on the precise role of infection in acute
      exacerbations of chronic bronchitis and on the overall benefit of antibiotic
      therapy of acute episodes, antibiotic therapy is considered an important part of
      the management of patients. It has to obey precise rules and obviously must be
      associated with preventive measures that can help to reduce both frequency and
      severity of acute exacerbations. The modifications of the susceptibility pattern
      to antibiotics of the two main bacteria involved deserve special attention to
      control the extension of the problem and define new therapeutic strategies. At
      present the currently recommended regimens are still valuable.

PMID- 9158751
TI  - Lower respiratory tract infections in the intensive care unit: consequences of
      antibiotic resistance for choice of antibiotic.
AB  - Pneumonia in the intensive care unit (ICU) has been associated with highly
      virulent pathogens that often exhibit resistance to multiple antibiotics and
      mortality rates of 30-70%. Pseudomonas aeruginosa and Enterobacteriaceae are the
      leading pathogens, followed by Staphylococcus aureus and polymicrobial
      etiologies. Recent clinical studies using monotherapy for nosocomial pneumonias
      resulted in low eradication rates for P. aeruginosa and staphylococci. An
      additional problem of these studies was the development of resistance by P.
      aeruginosa during the antibiotic treatment; also the selection of highly
      resistant strains like Xanthomonas maltophilia and Acinetobacter species was a
      major concern. However, several prospective studies comparing monotherapy versus
      combination therapy in nosocomial pneumonia of ICU patients have shown that a
      response rate of 60% is achievable, which is comparable to historic rates for
      combination therapy regimens. Only infections induced by P. aeruginosa, S.
      aureus, or other highly resistant pathogens (Acinetobacter, X. maltophilia, etc.)
      should be treated with well-defined antibiotic combinations.

PMID- 9158752
TI  - Penicillin-resistant and multidrug-resistant Streptococcus pneumoniae in a
      pediatric hospital in Zagreb, Croatia.
AB  - Sixty-four penicillin-resistant Streptococcus pneumoniae isolates
      [benzylpenicillin minimal inhibitory concentrations (MICs) between 0.05 and 1.6
      micrograms/ml] recovered at the Pediatric Hospital "Dr. Fran Mihaljevic" in
      Zagreb, Croatia between October 1990 and March 1993 were analyzed for serotype,
      antibiotic susceptibility patterns, and chromosomal relatedness using pulsed
      field gel electrophoretic (PFGE) analysis of chromosomal DNA fragmented by
      digestion with the SmaI endonuclease. Hospital "Dr. Fran Mihaljevic" services the
      capital of Croatia and its vicinity. Most of the isolates were from
      nasopharyngeal carriage, but several isolates were from otitis media, sinusitis,
      and meningitis. Most isolates belonged to either serotype 23F (36/64) or 19F
      (12/64); the rest, including three 15C isolates, were in 11 additional distinct
      serotypes. The overwhelming majority (25/36) of the serotype 23F isolates had
      penicillin MIC values of 1-2 micrograms/ml and shared variants of a common PFGE
      pattern, closely related to the PFGE identified in multiresistant pneumococci of
      the same serotype with wide geographic spread to Spain, Portugal, France, and the
      United States. This group of bacteria was also resistant to tetracycline,
      chloramphenicol, and sulfamethoxazole/trimethoprim. In contrast to the relative
      genetic and phenotypic homogeneity of the more highly penicillin resistant
      isolates, pneumococci with penicillin MICs between 0.5 and 0.4 microgram/ml
      (29/64) were distributed in 13 different serotypes and as many as 20 distinct
      PFGE patterns.

PMID- 9158754
TI  - Effects of combination of benzylpenicillin and fosfomycin on penicillin-resistant
      Streptococcus pneumoniae.
AB  - The in vitro activity of benzylpenicillin in combination with fosfomycin against
      51 clinical isolates of penicillin-resistant Streptococcus pneumoniae [minimal
      inhibitory concentrations (MICs) of benzylpenicillin > or = 0.5 mg/liter] was
      investigated. The fractional inhibitory concentration (FIC) index using the
      checkerboard method ranged from 0.38 to 0.75 (mean: 0.63). A synergy was also
      demonstrated in the killing curve on S. pneumoniae TW-1303 (MIC of
      benzylpenicillin, 2 mg/liter; MIC of fosfomycin, 32 mg/liter: FIC index, 0.38).
      Fosfomycin inhibited the production of all penicillin-binding proteins (PBP)
      except PBP 2B of S. pneumoniae TW-1303 and it decreased that of PBP 2B when it
      was combined with benzylpenicillin. These results suggest that the combination of
      benzylpenicillin and fosfomycin could be considered as the alternative treatment
      of penicillin-resistant pneumococcal infections.

PMID- 9158753
TI  - Conjugative mobilization of a vancomycin resistance plasmid by a putative
      Enterococcus faecium sex pheromone response plasmid.
AB  - Recent epidemiological evidence suggests that horizontal gene transfer may be an
      important mechanism for dissemination of vancomycin resistance. A filter mating
      survey of 21 VanA Enterococcus faecium isolates from The New York Hospital showed
      that 14 of these isolates transferred vancomycin resistance (Vmr) to the plasmid
      free reference strain Enterococcus faecalis JH2-2. One isolate, E. faecium R7,
      was selected for further study based on its ability to transfer Vmr to strain JH2
      2 in liquid culture. Analysis of the plasmid content of transconjugants revealed
      three general classes. The predominant class (28 of 47 transconjugants) contained
      two separate plasmids: pHKK702 and pHKK703. pHKK702 is a 41-kb plasmid that
      contains an element indistinguishable from the Vmr transposon Tn1546 and an
      element that hybridizes with an ermB probe from the Staphylococcus aureus
      erythromycin resistance transposon Tn551. pHKK703 is a 55-kb plasmid that
      hybridizes with probes for the sex pheromone response genes prgA, prgB, and prgX
      derived from the E. faecalis plasmid pCF10. The second group of transconjugants
      (18 of 47) contained various recombinant forms of pHKK702 and pHKK703, whereas a
      third transconjugant class contained only pHKK702 (1 of 47). Transconjugants that
      contained both pHKK702 and pHKK703 were able to efficiently transfer Vmr to
      recipient strains in broth or on filters. However, no transfer of Vmr was
      detected using the donor containing only pHKK702. The transfer of Vmr from the
      recombination-deficient derivative of E. faecalis JH2-2 [strain UV202(pHKK702,
      pHKK703)] was reduced 600-fold compared to that of JH2-2(pHKK702, pHKK703). We
      propose that pHKK703 functions as an E. faecium sex pheromone response plasmid
      that conjugatively mobilizes pHKK702, and that a major pathway for this
      mobilization may require donor-mediated recombination proficiency. This report
      provides the first example in which a plasmid containing a Tn1546-related element
      is conjugatively mobilized.

PMID- 9158755
TI  - Penicillin and beyond: evolution, protein fold, multimodular polypeptides, and
      multiprotein complexes.
AB  - As the protein sequence and structure databases expand, the relationships between
      proteins, the notion of protein superfamily, and the driving forces of evolution
      are better understood. Key steps of the synthesis of the bacterial cell wall
      peptidoglycan are revisited in light of these advances. The reactions through
      which the D-alanyl-D-alanine depeptide is formed, utilized, and hydrolyzed and
      the sites of action of the glycopeptide and beta-lactam antibiotics illustrate
      the concept according to which new enzyme functions evolve as a result of
      tinkering of existing proteins. This occurs by the acquisition of local
      structural changes, the fusion into multimodular polypeptides, and the
      association into multiprotein complexes.

PMID- 9158756
TI  - Penicillin-binding proteins as resistance determinants in clinical isolates of
      Streptococcus pneumoniae.
AB  - Altered penicillin-binding proteins (PBPs) with reduced affinity for penicillin
      are encoded by mosaic genes in penicillin-resistant clinical isolates of
      Streptococcus pneumoniae. Generally, members of one bacterial clone contain the
      same mosaic gene. We report here on a serotype 19A clone of penicillin- and
      multiple-resistant S. pneumoniae prevalent in Hungary, members of which are
      exceptionally diverse in terms of PBP properties. The pbp2x gene of four 19A
      isolates was sequenced, and a distinct mosaic structure detected in each case.
      The pbp2x genes also differed from a homologous gene of a high-level penicillin
      resistant S. mitis from Hungary. The contribution of PBPs to resistance
      development was studied on transformation experiments using the laboratory strain
      R6 as recipient, and PBP genes from the type 19A isolate Hu11. pbp2x and pbp2b
      function as primary resistance determinants for different beta-lactams. Secondary
      transformation with pbp1a increased the resistance level considerably for
      penicillins and cefotaxime. Chromosomal DNA of a high-level penicillin- and
      cefotaxime-resistant S. mitis from Hungary also transformed the R6 strain to
      increased resistance levels, and PBP2x and PBP2b functioned as primary resistance
      determinants as above. In contrast, high-level cefotaxime resistance appeared to
      be due to a low affinity PBP2a, indicating that this PBP can also function as a
      resistance determinant.

PMID- 9158757
TI  - Penicillin-binding proteins 2x and 2b as primary PBP targets in Streptococcus
      pneumoniae.
AB  - Different penicillin-binding proteins PBPs are affected in cefotaxime-resistant
      laboratory mutants compared to piperacillin-resistant mutants. PBP2x acts as the
      primary PBP target in cefotaxime-resistant mutants, whereas PBP2b is the primary
      target in piperacillin-resistant mutants. Depending on the mutations in PBP2x, it
      functions as a resistance determinant for cefotaxime only, or for penicillins as
      well. Mutations in PBP2x of laboratory mutants are found exclusively in the
      penicillin-binding domain that contains three homology boxes common to all
      penicillin-interacting enzymes. Most mutations relevant for resistance occur
      close to the SXN or the KT/SG box, or at the C-terminal end of the penicillin
      binding domain, similar to mutations described in PBP2b of laboratory mutants.
      Amino acid alterations occur at similar sites also in PBP2x of beta-lactam
      resistant clinical isolates and most of these proteins also contain changes in
      the SXXK box with the active site serine, suggesting that these alterations may
      be critical for resistance development in clinical isolates.

PMID- 9158758
TI  - Resistance determinants for beta-lactam antibiotics in laboratory mutants of
      Streptococcus pneumoniae that are involved in genetic competence.
AB  - Laboratory mutants of Streptococcus pneumoniae resistant to either cefotaxime or
      piperacillin reveal defects in competence development independent of the
      selective beta-lactam. A resistance determinant ciaH encoding a putative
      histidine kinase of a two-component signal-transducing system that is also
      involved in competence regulation was recently identified in cefotaxime-resistant
      mutants. We show now that the CiaH protein can be phosphorylated by ATP in vitro,
      and that it also phosphorylates the cognate response regulator CiaR. The mutant
      C306 containing the CiaH mutation Thr-230-Pro is completely noncompetent. It does
      not release competence-inducing activity (competence factor) into the medium nor
      can such an activity be released from the cells. Competence in C306 cannot be
      induced upon addition of external competence factor, in contrast to the
      competence-defective piperacillin-resistant mutants P506 and P408. A novel
      resistance determinant cpoA specific for piperacillin was identified in
      piperacillin-resistant mutants. CpoA is responsible for the competence defect in
      P506 but not in P408. The results document a tight link between the action of
      beta-lactams and competence development in the pneumococcus and confirm that the
      two beta-lactams piperacillin and cefotaxime act via different primary targets.

PMID- 9158759
TI  - Effects of penicillin-binding protein 4 overproduction in Staphylococcus aureus.
AB  - The pbp4 gene of a Staphylococcus aureus strain selected stepwise in vitro for
      growth on increasing concentrations of penicillin and of its susceptible parent
      strain showed overall identity except in the promoter region. In the mutant a
      deletion upstream of the pbp4 structural gene removed 90 nucleotides (nt) that
      were framed by a 12 nt inverted repeat. This deletion occurred in step 4 of the
      in vitro selection procedure and was paralleled by a significant increase in the
      penicillin-binding protein 4 (PBP4) production. The in vitro step selected mutant
      showed a remarkable increase in the cross-linking of the peptidoglycan compared
      to its parent. This was linked to morphological changes in the appearance of the
      cells, which were surrounded by a very thick and fuzzy cell wall.

PMID- 9158760
TI  - Glutamine synthetase and heteroresistance in methicillin-resistant Staphylococcus
      aureus.
AB  - Inactivation of femC in methicillin-resistant Staphylococcus aureus (MRSA)
      results in lowered methicillin resistance and a reduction in the amidation of the
      iso-D-glutamate of the peptidoglycan stem peptide. The femC phenotype is due to
      insertional inactivation of the glutamine synthetase repressor gene glnR by
      Tn551, which has a polar effect on glutamine synthetase (glnA) transcription. The
      complete glutamine synthetase operon (glnRA) of S. aureus was cloned and
      sequenced, and its transcriptional start was determined. The deduced amino acid
      sequence of the staphylococcal glutamine synthetase showed 76% identity and 87%
      similarity to the Bacillus subtilis glutamine synthetase. The staphylococcal
      glnRA operon was shown to complement an Escherichia coli glutamine synthetase
      negative mutant and to restore methicillin resistance in femC mutants. femC
      mutants revert to resistance in the presence of high concentrations of
      methicillin. These revertants, which still carried the femC lesion, were shown to
      retain the lowered amidation of the iso-D-glutamate peptidoglycan stem peptide. A
      new chromosomal locus hmrC was postulated to have mutated to allow expression of
      high methicillin resistance in these femC revertants. Although the highly
      resistant hmrC revertant resembled phenotypically the highly methicillin
      resistant subclones occurring in heterogeneously resistant MRSA, we could show by
      transduction that the locus hmrC was distinct from chr*, a chromosomal site
      postulated to confer high methicillin resistance in heterogeneous MRSA. This
      suggests that S. aureus can adopt multiple ways to achieve high methicillin
      resistance.

PMID- 9158761
TI  - Intrinsic penicillin resistance in enterococci.
AB  - Penicillin resistance development in enterococci has been associated with
      overproduction of a low-affinity penicillin-binding protein (PBP) that is a
      normal component of the PBP pattern of these bacteria and is apparently able to
      substitute the functions of the other PBPs. In resistant mutants of Enterococcus
      hirae ATCC 9790 the low-affinity PBP (PBP5) overproduction was associated with a
      deletion in a genetic element, located 1 kb upstream of the pbp5 gene, which
      negatively controlled PBP5 synthesis. Hypersusceptibility to penicillin was
      associated with a point mutation in the pbp5 gene, which causes premature
      termination of translation. Structural homologies between low-affinity PBPs of
      the different enterococcal species have been suggested by cross-reactivity of
      antibodies raised against E. hirae PBP5 with PBP5 of Enterococcus faecium and
      Enterococcus faecalis. Acquisition of a high-level ampicillin resistance in E.
      faecium was associated with overproduction of PBP5, which, compared with PBP5 of
      moderately resistant strains, appeared to be modified in its penicillin-binding
      capability. The modified phenotype of PBP5 was found to be associated to some
      amino acid substitutions in the region between the SDN and KTG motifs. In
      particular, the substitution converting a polar residue (T) in a nonpolar one (A
      or I) could play an important role in remodeling the penicillin-binding domain
      and determining the decrease in penicillin affinity.

PMID- 9158762
TI  - The gene encoding for penicillin-binding protein 5 of Enterococcus faecalis is
      useful for development of a species-specific DNA probe.
AB  - Recently, in Escherichia coli was cloned a Sau3AI 3.4-kb fragment containing the
      gene encoding for penicillin-binding protein 5 (PBP5) of Enterococcus faecalis.
      The structural gene for the PBP of E. faecalis and the flanking regions were
      entirely sequenced (C. Signoretto, M. Boaretti, and P. Canepari, FEMS Microbiol.
      Lett. 123:99-106, 1994). When the entire cloned E. faecalis DNA insert, labeled
      with digoxigenin, was used as a probe to detect a homology gene in enterococci,
      it was observed that only DNAs of all the E. faecalis strains reacted to the
      probe. The same results were obtained when a HindIII fragment of 0.35 kb from the
      entire insert of 3.4 kb was used. In this study we tested a total of 62
      clinically isolated enterococcal strains, belonging to the species E. faecalis
      (36 strains), E. faecium (13), E. gallinarum (6), E. bovis (2) E. avium (3), E.
      hirae (1), and E. casseliflavus (1). The results indicate that both the entire
      segment and the HindIII fragment may be useful for preparing a species-specific
      probe for rapid identification of E. faecalis species.

PMID- 9158763
TI  - Genetics of glycopeptide resistance in enterococci.
AB  - Glycopeptide resistance in enterococci is phenotypically and genotypically
      heterogeneous. The genes responsible for inducible resistance to high levels of
      vancomycin and teicoplanin (VanA phenotype) are carried by the 10,851-bp Tn1546
      transposon. Transposition of Tn1546 into self-transferable plasmids and
      subsequent transfer by conjugation appears to be responsible for the
      dissemination of this type of resistance. Nine polypeptides are encoded by Tn1546
      that belong to five functional groups: transposition functions (ORF1 and ORF2),
      regulation of resistance gene expression (VanR and VanS), synthesis of
      depsipeptide D-Ala-D-lactate (VanH and VanA), hydrolysis of D-Ala-D-Ala
      containing peptidoglycan precursors (VanX and VanY), and low-level teicoplanin
      resistance (VanZ). VanB-type resistance (various levels of resistance to
      vancomycin and susceptibility to teicoplanin) is also due to production of D-Ala
      D-Lac. The VanB ligase of VanB-type strains is structurally and functionally
      similar to VanA. The vanB gene was found on composite transposon Tn1547, which,
      in turn, was part of larger conjugative chromosomally located elements (90 to 250
      kb). In contrast to acquired VanA- and VanB-type resistance, VanC-type resistance
      (low level of resistance to vancomycin and susceptibility to teicoplanin) is an
      intrinsic property of motile enterococci. Resistance in these species is due to
      synthesis of dipeptide D-Ala-D-Ser by VanC ligases leading to production of cell
      wall precursors with reduced vancomycin affinity.

PMID- 9158764
TI  - Peptidoglycan composition of vancomycin-resistant Enterococcus faecium.
AB  - Muropeptide composition of peptidoglycan isolated from isogenic vancomycin
      resistant and sensitive Enterococcus faecium strains was analyzed by reverse
      phase high-performance liquid chromatography combined with amino acid and fast
      atom bombardment mass spectrometric analyses. Peptidoglycan of the sensitive and
      resistant strains was the same and was composed of tri- and tetrapeptides stem
      peptide subunits with or without aspartate or asparagine substitutions on the
      epsilon-amino group of the lysine residue. Thus, the synthesis of lactate
      terminating peptidoglycan precursors in vancomycin-resistant E. faecium did not
      affect the chemical composition of peptidoglycan.

PMID- 9158765
TI  - Genotypic characterization of a nosocomial outbreak of VanA Enterococcus
      faecalis.
AB  - Despite growing concern about vancomycin-resistant enterococci (VRE) as
      nosocomial pathogens, especially in the United States, in Italy VRE still
      represent an uncommon and occasional experience for most diagnostic laboratories.
      We report a genotypic characterization of the first reported nosocomial outbreak
      of VRE in Italy. Some experiments, including plasmid analysis and pulsed-field
      gel electrophoresis (PFGE) assays, aimed at investigating the genetic relatedness
      of the VRE isolates. Other experiments, based on hybridization and polymerase
      chain reaction (PCR) assays, aimed at characterizing the vancomycin resistance
      determinants. Over a 6-month period, 21 VRE, all identified as Enterococcus
      faecalis, were isolated from eight patients (all treated earlier with
      glycopeptide antibiotics) in a neurosurgical intensive care unit. All isolates
      had the same biochemical profile and antibiotic susceptibility pattern, including
      high-level resistance to aminoglycosides and vancomycin and teicoplanin MICs of
      256 and 128 micrograms/ml, respectively. Three plasmids, one strongly hybridizing
      with a vanA probe, were detected in all but the last of the 21 VRE isolates. The
      last isolate of the cluster lacked the smallest of the three plasmids. Similar
      restriction profiles were obtained after plasmid DNA digestion with several
      endonucleases, with minor differences appreciated only in the first and last
      isolates. Analysis of genomic DNA restriction fragment patterns by PFGE confirmed
      that the reported cluster of VRE isolations was due to a single nosocomial strain
      of E. faecalis, despite some modifications in plasmid DNA at the beginning and at
      the end of the outbreak. Completely different PFGE patterns were yielded by
      vancomycin-susceptible E. faecalis strains isolated during the same period from
      inpatients in the same intensive care unit. Hybridization experiments with vanA
      and vanS-vanH probes and DNA amplification assays using 14 PCR primer pairs
      specific for vanA cluster genes (vanR, vanS, vanH, vanA, and vanY), orf1, orf2,
      vanB, and vanC showed identical organization of resistance determinants in all
      epidemic VRE isolates. This organization appeared to be the same as that
      described for Tn1546 in VanA prototype strain E. faecium BM4147.

PMID- 9158766
TI  - An electron microscopic study of clinical and laboratory-derived strains of
      teicoplanin-resistant Staphylococcus haemolyticus.
AB  - Staphylococcal resistance to glycopeptides (which involves more teicoplanin than
      vancomycin) is uncommon and largely confined to Staphylococcus haemolyticus, an
      emerging nosocomial pathogen with a tendency to develop antibiotic resistance. In
      this study, six S. haemolyticus strains, including two isogenic pairs of
      teicoplanin-susceptible/-resistant strains and two resistant clinical isolates,
      were used in a morphologic and morphometric electron microscope investigation.
      Cells from both clinical and laboratory-derived teicoplanin-resistant strains
      exhibited abnormally roughened, irregular outlines when observed by transmission
      electron microscopy. However, no significant differences in cell wall thickness
      resulted from morphometric analysis when the susceptible/resistant cells of the
      two isogenic pairs were compared. By scanning electron microscopy, an abnormally
      roughened, blistered surface was associated with teicoplanin-resistant cocci. A
      certain variability was noted between strains, not clearly related to the
      resistance level. In freeze-fracture investigations, a higher number per square
      micrometer of intramembrane particles, more significant in the E than in the P
      membrane fracture face, was observed in the laboratory-derived resistant clones
      as compared to susceptible parent strains. Further studies are needed to
      understand the cause-effect relation between these ultrastructural alterations
      and staphylococcal resistance to teicoplanin (but not to vancomycin).

PMID- 9158767
TI  - The Aeromonas metallo-beta-lactamases: genetics, enzymology, and contribution to
      drug resistance.
AB  - Aeromonads are environmental microorganisms that can be responsible for both
      human and animal infections. Individual Aeromonas strains can produce up to three
      different, inducible, chromosomally encoded beta-lactamases, including a group 1
      molecular class C cephalosporinase, a group 2d molecular class D penicillinase,
      and a group 3 molecular class B metallo-beta-lactamase, which contribute to beta
      lactam resistance in members of this genus. Among these enzymes, the metallo-beta
      lactamases are clinically relevant because of their ability to hydrolyze
      carbapenem antibiotics, and also represent a relevant investigational model for
      studying molecular class B beta-lactamases because of their unique enzymological
      behavior. An overview on the distribution, genetics, and enzymology of these
      enzymes is reported, and the contribution of these enzymes to microbial drug
      resistance is also discussed.

PMID- 9158768
TI  - Overproduction and purification of the Aeromonas hydrophila CphA metallo-beta
      lactamase expressed in Escherichia coli.
AB  - The Aeromonas hydrophila CphA metallo-beta-lactamase was overexpressed in a
      soluble secreted form in Escherichia coli using a T7 RNA polymerase-based
      expression system, and a simple protocol based on a single cation-exchange
      chromatographic step was developed, which is suitable for rapid purification of
      the overexpressed enzyme from E. coli lysates. A yield of up to 30 micrograms of
      purified enzyme per milliliter of culture was obtained. The purified enzyme
      preparation showed properties identical to those previously reported in the
      literature.

PMID- 9158769
TI  - Borderline susceptibility to methicillin in Staphylococcus aureus: a new
      mechanism of resistance?
AB  - Staphylococcus aureus strains with borderline levels of susceptibility or
      resistance to antistaphylococcal penicillinase-resistant penicillins (PRPs) were
      initially reported as neither heteroresistant nor multiply resistant organisms,
      producing large amounts of beta-lactamase, and becoming fully susceptible to PRPs
      in the presence of beta-lactamase inhibitors. This borderline susceptibility or
      low-level resistance was suggested to be due to beta-lactamase hyperproduction:
      according to this hypothesis, the staphylococcal beta-lactamase, when
      hyperproduced, would succeed in partially hydrolyzing methicillin and related
      PRPs. However, later studies demonstrated that borderline PRP susceptibility
      cannot be explained soley on this basis, beta-lactamase hyperproduction being
      neither sufficient nor necessary to determine the borderline phenotype. Intrinsic
      mechanisms have also been reported to be associated with some borderline PRP
      susceptible S. aureus strains. The more recent discovery of a PRP-hydrolyzing
      beta-lactamase (methicillinase) produced, in addition to the conventional
      penicillinase, by borderline S. aureus strains suggests that this second, more
      specific beta-lactamase is more likely to be responsible for the borderline
      phenotype than an increased amount of the penicillinase. The slow kinetics of PRP
      hydrolysis by methicillinase is consistent with its association with reduced
      susceptibility rather than true resistance to PRPs. The combined effect of
      methicillinase plus penicillinase on some common substrates might explain the
      increased beta-lactamase activity often observed in borderline S. aureus strains.

PMID- 9158770
TI  - The role of the nonconserved residues at position 167 of class A beta-lactamases
      in susceptibility to mechanism-based inhibitors.
AB  - Differences in specificities between the class A beta-lactamases for both
      substrate and inhibitors are known. The role of the nonconserved amino acid
      residue at position 167 of the class A enzyme, which forms a cis bond with the
      catalytically essential Glu-166 residue, in both the hydrolysis of beta-lactam
      substrates and inactivation by mechanism-based inhibitors, was investigated. Site
      directed mutagenesis was performed on the penPC gene encoding the Bacillus cereus
      569/H beta-lactamase I to replace thr-167 with the corresponding Staphylococcus
      aureus PC1 residue Ile. Kinetic data obtained from the purified Thr-167-Ile B.
      cereus 569/H beta-lactamase was compared to that obtained from the wild-type B.
      cereus and S. aureus enzymes and indicated that the replacement had little effect
      on the Michaelis parameters for the hydrolysis of S- and A-type penicillins.
      However, the Thr-167-Ile enzymes became more S. aureus PC1-like in its response
      to the mechanism-based inhibitors clavulanic acid and 6-beta-(trifluoromethane
      sulfonyl)amidopenicillanic acid sulfone. A model for the role of this
      nonconserved residue at position 167 in the mechanism of inactivation by
      mechanism-based inhibitors is proposed.

PMID- 9158771
TI  - beta-Lactamases are absent from Archaea (archaebacteria).
AB  - beta-Lactamases, enzymes that hydrolyze and inactive beta-lactam antibiotics, are
      of widespread occurrence in Bacteria and are related to the metabolism of
      bacterial cell wall murein. So far, no information exists on beta-lactamases in
      Archaea, a separate domain of prokaryotes with diverse types of unique cell wall
      polymers. Different mesophilic methanogenic and extremely halophilic Archaea
      containing methanochondroitin, pseudomurein, or S-layer protein or glycoprotein
      cell walls, were tested for beta-lactamase activity with the chromogenic beta
      lactam nitrocefin as substrate. Also tested were representative microbial Eucarya
      from algae, yeasts, and protozoa. No beta-lactamase activity was detected in any
      of the archaeal and eukaryotic organisms. This supports the view that beta
      lactamases are restricted to the domain of Bacteria.

PMID- 9158772
TI  - Diffusion of carbapenems through the outer membrane of enterobacteriaceae and
      correlation of their activities with their periplasmic concentrations.
AB  - Scarce information is available on the real mechanism by which carbapenemes
      penetrate in Enterobacteriaceae, although a considerable amount of evidence
      suggests that in many species of this family the lack of certain outer membrane
      proteins is associated with the acquisition of resistance to these antibiotics.
      The existance of specific pathways for the carbapenems has never been
      demonstrated, although at times it has been postulated in both wild and mutant
      strains, on the basis of evident discordances between permeability patterns and
      suceptibility data. By using the Zimmerman and Rosselet technique, which requires
      the strain under investigation to harbor a suitable beta-lactamase, the
      permeability of intact Escherichia coli and Enterobacter cloacae cells to
      meropenem and imipenem was investigated by transferring a constructed vector
      carrying the carbapenem hydrolyzing CphA metallo-beta-lactamase gene into the
      parental strains and their porin-deficient mutants. Reduced amounts of
      nonspecific porins significantly reduced the penetration of both carbapenems. The
      virtual absence of porins caused the MICs of meropenem to increase, mostly in
      Enterobacter cloacae, while it did not affected the MICs of imipenem. No evidence
      of specific porin pathways of the type described in Pseudomonas aeruginosa was
      found.

PMID- 9158773
TI  - A phosphoglucomutase-like gene essential for the optimal expression of
      methicillin resistance in Staphylococcus aureus: molecular cloning and DNA
      sequencing.
AB  - We describe here the cloning and sequencing of a new auxiliary gene identified by
      Tn551 insertional mutagenesis of the highly and homogeneously methicillin
      resistant Staphylococcus aureus strain COL. The insertionally inactivated mutant
      RUSA315 had intact mecA and normal amounts of PBP2A, but drastically reduced
      antibiotic resistance (drop in methicillin MIC from 1600 to 1.5 micrograms ml-1),
      a unique heterogeneous phenotype, and a compositional change in the cell wall
      characterized by the complete disappearance of the unsubstituted disaccharide
      pentapeptide from the peptidoglycan. Cloning in E. coli followed by sequencing
      located the Tn551 insert omega 720 in an open reading frame of 451 codons,
      provisionally called femR315, defining a polypeptide with a deduced amino acid
      sequence that showed over 26% sequence identity and 57% overall sequence
      similarity with the phosphoglucomutase (PGM) gene of E. coli. The Tn551 insertion
      site of a previously described mutant 12F (femD) also lies in the same gene as
      femR315. The wild-type form of femR315 subcloned in a shuttle vector fully
      restored expression of high level (parental) methicillin resistance in mutant
      RUSA315. The exact biochemical function of femR315 is not known. However, enzymes
      similar to PGM catalyze the isomerization of hexose and hexosamine phosphates
      leading to the formation of glucosamine-1-P, which is an obligate precursor in
      the biosynthesis of UDP-N-acetylglucosamine (UDP-NAGA). We propose that the
      suppression of methicillin resistance in RUSA315 is related to some functional or
      quantitative abnormality of UDP-NAGA metabolism.

PMID- 9158774
TI  - Multiple-resistant enterococci and gram-negative bacteria: tracking gene
      dissemination.

PMID- 9158775
TI  - Molecular epidemiology of integron-associated antibiotic resistance genes in
      clinical isolates of enterobacteriaceae.
AB  - The epidemiology of integron-mediated antibiotic-resistant genes in clinical
      enterobacteria from a single location was investigated. Forty-nine isolates
      (kindly provided by Dr. D. Sirot, Clermont-Ferrand, France) were selected for
      transferable resistance to aminoglycosides or to other antibiotics. Total DNA
      prepared from these strains was screened for the presence of conserved segments
      of integrons by PCR. The nature and frequency of inserted resistance gene
      cassettes were determined by direct nucleotide sequencing and were related to the
      resistances expressed by the strain. Integron hot-spots were present in 59% of
      the strains from 6 species, in either one or two copies. For amplicons sequenced,
      one or two antibiotic-resistant genes were found in various combinations, and
      were always expressed at the phenotypic level. They included the aminoglycoside
      resistance genes ant(3")-Ia and aac(6')-Ib (75%), as well as dhfr-I,-VII (21.4%)
      and blaOXA-1 (3.6%). Almost half of the transferable resistance to
      aminoglycosides (53%) was mediated by integron hot-spots in strains characterized
      at the nucleotide level. The proportion rose to 100% for the AAC(6')-I resistance
      profile. This study emphasizes the important contribution of integrons to
      aminoglycoside resistance within enterobacteria from a clinical setting.

PMID- 9158776
TI  - A transferable multiple drug resistance plasmid from Vibrio cholerae O1.
AB  - Ten multiple antimicrobial-resistant isolates of Vibrio cholerae O1 isolated from
      patients in Uganda were characterized, and the transferability of resistance to
      bacteria of diverse origins was investigated. The isolates were toxigenic and
      belonged to biotype E1 Tor, serotype Ogawa, and ribotype 8, and possessed a 130
      MDa plasmid of incompatibility group 6-C. This plasmid, designated pRVC1, was
      shown to confer resistance to trimethoprim (mediated by a dhfrI gene),
      sulfonamides (a suII gene), tetracycline [a tet(C) gene], chloramphenicol (a catI
      gene), ampicillin (a beta-lactamase gene other than blaTEM or blaSHV), and
      streptomycin. pRVC1 proved to be transmissible at frequencies between 1 x 10(-1)
      and 5 x 10(-6) transconjugants per recipient to a variety of bacterial pathogens,
      including those of humans, animals, and fish. Most efficient transfer was
      observed from V. cholerae to strains of Shigella flexneri, Escherichia coli,
      Vibrio parahaemolyticus, and three Aeromonas species. The present in vitro study
      suggests that pRVC1 may spread from V. cholerae to other bacteria pathogenic to
      man, animals, and fish in natural environments.

PMID- 9158777
TI  - Identification of DNA gyrase A mutations in ciprofloxacin-resistant isolates of
      Salmonella typhimurium from men and cattle in Germany.
AB  - Six multiply resistant isolates of Salmonella typhimurium var. copenhagen with
      high-level resistance to fluoroquinolones (e.g., MIC of ciprofloxacin: 32
      micrograms/ml) were isolated from human patients (n = 3) and from cattle (n = 3).
      The isolates were examined by complementation tests using a set of broad-host
      range plasmids, which carry either the gyrA+ or the gyrB+ genes or a combination
      of both from Escherichia coli K-12. The results indicated a combination of gyrA
      and gyrB mutations in all isolates. Subsequent direct sequencing of PCR-generated
      internal DNA fragments of gyrA revealed an identical double mutation in all six
      isolates (Ser-83-->Ala and Asp-87-->Asn). In addition, the results of phenotypic
      (i.e., phagetype, biotype, serotype) and genotypic characterization [i.e.,
      ribotyping and polymerase chain reaction fingerprinting (PCR-fingerprinting)]
      were identical for all six isolates and were distinguishable from a quinolone
      susceptible strain of the same serovar and an unrelated isolate of S.
      typhimurium. These data indicate the clonal identity of the fluoroquinolone
      resistant strains of S. typhimurium isolated from men and cattle in Germany.

PMID- 9158778
TI  - Risk factor assessment for the acquisition of fluoroquinolone-resistant isolates
      of Pseudomonas aeruginosa in a community-based hospital.
AB  - A case-control study was performed in a community-based nonteaching hospital to
      assess patient risk factors for the acquisition of fluoroquinolone-resistant
      isolates of Pseudomonas aeruginosa. Fifty-five patients who were hospitalized
      between July 1, 1993 and December 31, 1993 and who had P. aeruginosa recovered
      from a clinical specimen were included in the analysis. Two patient populations
      were designated based on the fluoroquinolone susceptibility of their P.
      aeruginosa isolates. Statistical evaluation using univariate analysis of
      demographic and clinical data from the 42 patients with quinolone-susceptible P.
      aeruginosa and the 13 patients with quinolone-resistant P. aeruginosa
      demonstrated that prior receipt of a fluoroquinolone was the only significant
      risk factor for the subsequent emergence of fluoroquinolone resistance among P.
      aeruginosa isolated from patients hospitalized in this small community-based
      institution (p = 0.0196). Multivariate analysis supported the finding that prior
      receipt of a fluoroquinolone was the major risk factor for the isolation of
      fluoroquinolone-resistant P. aeruginosa (p = 0.0004); isolation of this Gram
      negative bacillus from sputum (p = 0.0306) and a history of recent surgery (p =
      0.0058) were also significantly associated as risk factors for resistance.

PMID- 9158779
TI  - Quinupristin/dalfopristin: spectrum of activity, pharmacokinetics, and initial
      clinical experience.
AB  - In recent years, the prevalence of multiple drug-resistant strains of common Gram
      positive pathogens has grown in many regions of the world. Increasingly,
      methicillin-resistant Staphylococcus aureus, coagulase-negative staphylococci,
      vancomycin-resistant enterococci, and penicillin-resistant pneumococci have been
      identified as causative organisms in serious and life-threatening infections.
      This increase in resistance highlights the need for new antimicrobial agents to
      expand the therapeutic armamentarium. Quinupristin/dalfopristin is the first of a
      unique class of antibiotics called streptogramins. It is characterized by a
      unique mechanism of action, intracellular activity, synergistic activity of its
      components, broad spectrum of activity against most Gram-positive cocci, common
      respiratory pathogens, and anaerobes, and demonstrated postantibiotic effect.
      Clinical evidence to date indicates that quinupristin/dalfopristin may be
      effective for the treatment of multidrug-resistant infections, especially those
      due to vancomycin-resistant enterococci and methicillin-resistant staphylococci.
      This article reviews the pharmacology, microbiology, and clinical experience with
      quinupristin/dalfopristin to date.

PMID- 9158780
TI  - Plasmid-mediated vanB glycopeptide resistance in enterococci.
AB  - Enterococcus faecium, which was highly resistant to vancomycin (MIC 256
      mg/liter), but susceptible to teicoplanin (MIC 2 mg/liter), caused two distinct
      episodes of infection on a renal unit in the United Kingdom. Pulsed field gel
      electrophoresis (PFGE) indicated that a single strain caused the first episode,
      while the second episode, which occurred 1 year later, involved multiple strains,
      all of which were distinct from the original strain. Vancomycin resistance in all
      but one of these strains was mediated by transferable plasmids that carried the
      vanB glycopeptide resistance gene. Transfer either of resistance plasmids or the
      vanB resistance determinant itself to different strains occurred during the
      second episode. Plasmid-mediated vanB resistance has not been widely documented.
      A retrospective study of a reference collection revealed two other vanB-encoding
      plasmids from an E. faecalis and an E. faecium referred from two further UK
      centers. Although restriction analysis indicated no similarity between the
      plasmids from the three different centers, all contained a 2.1-kb EcoRV fragment
      that hybridized with a probe for the vanB gene. This suggests that there has been
      dissemination of a conserved glycopeptide resistance determinant, of which vanB
      is a part.

PMID- 9158781
TI  - Serious infections caused by multiply-resistant Enterococcus faecium.
AB  - Three liver transplant patients developed serious intraabdominal infections and
      recurrent bacteremias due to strains of Enterococcus faecium with high-level
      resistance to vancomycin. The enterococci were also resistant to all other
      antibacterials except pristinamycin, which, given orally, proved ineffective. One
      strain was sensitive to tetracycline. Increasingly, clinicians are likely to
      encounter infections caused by multiply-resistant enterococci, and these cases
      illustrate the seriousness of such infections in compromised patients.

PMID- 9158782
TI  - Quinupristin/dalfopristin (RP 59500) therapy for vancomycin-resistant
      Enterococcus faecium aortic graft infection: case report.
AB  - A 46-year-old woman was admitted to the hospital with severe peripheral vascular
      disease, requiring multiple vascular surgical procedures. During the sixth
      hospital week, after prior therapy with multiple antibiotics, Enterococcus
      faecium was isolated as the only organism from an operating room culture of an
      infected aortic graft. Histological examination of the graft showed infiltration
      with polymorphonuclear leukocytes. Subsequently, cultures of an infected inguinal
      wound yielded Enterococcus faecium with mixed bacterial growth. Both isolates of
      Enterococcus faecium were resistant to all available antimicrobials, including
      ampicillin, vancomycin, tetracycline, chloramphenicol, and ciprofloxacin.
      Compassionate use therapy with quinupristin/dalfopristin (RP59500) was
      administered for 25 days, the patient's clinical condition improved, and wound
      healing occurred. Transient elevation of serum alkaline phosphatase was noted.
      This case demonstrates successful eradication of deep VREF infection by
      quinupristin/dalfopristin with good tolerance of prolonged therapy.

PMID- 9158783
TI  - Successful treatment of persistent bacteremia due to vancomycin-resistant,
      ampicillin-resistant Enterococcus faecium.
AB  - Emergence of vancomycin-resistant enterococci has become an increasing problem in
      many medical centers. We report a liver transplant recipient with vancomycin
      resistant Enterococcus faecium bacteremia who was successfully treated using very
      high dose continuous infusion ampicillin/sulbactam, plus gentamicin after he
      remained bacteremic on high dose ampicillin and gentamicin. At our institution,
      83% of E. faecium isolates from 1994 were inhibited by ampicillin/sulbactam
      compared to 66% for ampicillin at an MIC < or = 64 micrograms/ml. None of these
      strains produced beta-lactamase, suggesting sulbactam may have an unexplained
      beneficial effect against some enterococci. Although an MIC of < or = 8
      micrograms/ml is required for ampicillin to be considered active against
      enterococci, much higher levels of ampicillin or ampicillin/sulbactam are safely
      achievable. The response of our patient and the reported in vivo data have
      implications for future treatment of this pathogen, and may necessitate a
      reevaluation of susceptibility interpretation guidelines by clinical
      laboratories, and therapeutic drug dosing by clinicians.

PMID- 9158784
TI  - Occurrence of glycopeptide resistance among Enterococcus faecium isolates from
      conventional and ecological poultry farms.

PMID- 9158785
TI  - Glycopeptide-resistant Enterococcus faecium outside Hospitals: a commentary.

PMID- 9158787
TI  - Survey of antimicrobial resistance in bacterial isolates from diseased cattle in
      France.
AB  - Since 1982, a national veterinary network has been involved in the monitoring of
      resistance to antimicrobial agents in the main pathogenic bacteria isolated from
      diseased cattle in France. It is based on 40 regional veterinary diagnostic
      laboratories and managed by a central reference laboratory (CNEVA Lyon). Highly
      standardized methods are used in the diagnostic laboratories. This network
      collects up-to-date information on antimicrobial resistance in veterinary
      isolates and gathers strains for specific studies on fastidious bacteria and for
      the analysis of mechanisms of resistance to antibiotics. Such a permanent survey
      is essential to establish a rational veterinary antibiotic policy. It could be
      connected to other compatible systems developed in other fields such as human
      medicine, food, and environment, to evaluate the importance of resistance and R
      factors spread for public health. The limits and perspectives of this
      surveillance system are discussed.

PMID- 9158786
TI  - Enterococcus faecium strains with vanA-mediated high-level glycopeptide
      resistance isolated from animal foodstuffs and fecal samples of humans in the
      community.
AB  - The occurrence and the further spread of high-level glycopeptide-resistant, vanA
      positive Enterococcus faecium strains outside of hospitals have been
      investigated. We could isolate such bacteria directly from thawing liquids of
      commercially produced frozen poultry (chickens, turkeys; no further data on
      previous feeding with avoparcin were available). In 5 of 13 samples of raw minced
      meat of pigs originating from 13 different butcher's shops, glycopeptide
      resistant E. faecium (VanA type) could be detected after overnight broth
      cultivation of these samples. No glycopeptide-resistant enterococci could be
      isolated from meat samples of chickens that were fed without avoparcin. VanA type
      E. faecium strains were also identified in 12 fecal samples recovered from 100
      nonhospitalized humans in the rural area of Saxony-Anhalt federal county. These
      results suggest a possible role of the food chain in the spread of glycopeptide
      resistant E. faecium. Molecular typing (macrorestriction and multilocus enzyme
      analysis) reveal a wide dissemination of the vanA gene among strains of different
      ecological origins.

PMID- 9158788
TI  - Rene Dubos: a harbinger of microbial resistance to antibiotics.

PMID- 9158789
TI  - Quinolone resistance mutations in the gyrA gene of clinical isolates of
      Salmonella.
AB  - S. typhimurium AlhR, S. enteritidis OulR, and S. hadar GueR resistant to
      fluoroquinolones (QR), ciprofloxacin MICs, 0.25 to 1 microgram/ml; norfloxacin
      MICs, 0.5 to 4 micrograms/ml; nalidixic acid MIC, 256 micrograms/ml were isolated
      from urinary tract infections (AlhR and OulR) during FQ therapy in
      immunocompromised patients infected by the parent FQ-susceptible strains (AlhS
      and OulS) (ciprofloxacin MICs, 0.032-0.063; norfloxacin MICs, 0.125-0.25;
      nalidixic acid MICs, 4-8) or from intestinal infection (GueR). Transformation of
      AlhR, OulR, and GueR by plasmid pJSW101 carrying the wild-type gyrA gene of
      Escherichia coli resulted in complementation (nalidixic acid MICs, 4 to 8),
      proving that these strains had a gyrA mutation. A 800-bp fragment of gyrA from
      the five strains was amplified by PCR. Direct DNA sequencing of 252-bp region of
      this fragment identified a single point mutation leading to a substitution Ser-83
      to Tyr in AlhR and to a substitution Ser-83 to Phe in OulR and in GueR. These
      results emphasize the potential risk of selection of FQ-resistant Salmonella
      during FQ therapy in immunocompromised patients and suggest that these strains
      differ from the parent strains at least by one mutation in the gyrA gene. They
      also confirm the role of substitutions in position 83 of gyrA in FQ-resistant
      clinical isolates of Salmonella.

PMID- 9158790
TI  - Albendazole resistance in Giardia is correlated with cytoskeletal changes but not
      with a mutation at amino acid 200 in beta-tubulin.
AB  - Albendazole resistance was induced in three different Giardia cultures following
      growth in successively increasing amounts of drug. One of the lines was
      previously resistant to high levels of metronidazole and was able to grow in 2
      microM albendazole. The other two survived exposure to 0.8 microM, while normally
      lethal levels of albendazole against Giardia in vitro were around 0.1-0.2 microM.
      Albendazole-resistant Giardia were cross-resistant to parbendazole. Major
      chromosome rearrangements were evident in the line resistant to 2 microM
      albendazole and IFA with antitubulin antibody indicated differences in the
      cytoskeleton, particularly the median body, between sensitive and resistant
      lines. This implicates the cytoskeleton in the mechanism of resistance.
      Substitution of Tyr for Phe is a consistent beta-tubulin amino acid change in the
      benzimidazole-resistant helminths and fungi so far analyzed. PCR primers were
      designed from the published Giardia beta-tubulin gene sequence and spanned the
      region encoding Phe at position 200. Sequence data from albendazole-resistant
      Giardia demonstrated that the beta-tubulin gene did not carry a mutation in the
      codon for amino acid 200. These data suggest that Phe at position 200 in beta
      tubulin is not necessary for benzimidazole resistance.

PMID- 9158791
TI  - Multiplicity of genetic backgrounds among vancomycin-resistant Enterococcus
      faecium isolates recovered from an outbreak in a New York City hospital.
AB  - A total of 182 vancomycin-resistant Enterococcus faecium and 6 Enterococcus
      faecalis inpatient isolates recovered during a 2-year period (1990-1992) in a New
      York City hospital were analyzed by molecular fingerprinting techniques, pulsed
      field gel electrophoresis (PFGE), of chromosomal SmaI digests combined with
      Southern hybridization using vanA and vanB2-specific DNA probes. Of the 180
      isolates hybridizing with these probes, 153 carried the vanA and 27 the vanB
      gene. As many as 21 different PFGE types and a total of 54 subtypes were
      identified among the isolates, and the size of vanA and vanB-hybridizing DNA
      fragments also showed a wide range of sizes, from about 37 to over 280 kb (in
      vanA) or 140 kb (in vanB), suggesting extensive recombination, including
      chromosomal integration, of the resistance genes in the isolates. Close to one
      third, 46, of the 148 isolates from 1992 belonged to two closely related PFGE
      subtype variants, each of which carried a 48 kb vanA hybridizing DNA fragment.
      Spread of this clone appears to be mainly responsible for the substantial
      increase in the prevalence of vancomycin-resistant E. faecium in early 1992.

PMID- 9158792
TI  - Tracing the origin of an outbreak of methicillin-resistant Staphylococcus aureus
      infections in a Portuguese hospital by molecular fingerprinting methods.
AB  - Seventy-six methicillin-resistant Staphylococcus aureus (MRSA) isolates were
      collected from July 1992 to May 1995 at a 400-bed district hospital in the
      northeast of Portugal. During the second half of the surveillance period, in July
      of 1994, an outbreak was detected in the orthopedic ward. Thirty-three (out of
      the 76) MRSA strains were recovered only in this ward during the outbreak period.
      All strains were characterized by a variety of genomic fingerprints.
      Hybridization of ClaI and SmaI restriction digests with the mecA- and Tn554
      specific DNA probes was used to identify polymorphism and determine chromosomal
      location of these determinants, and pulsed-field gel electrophoretic analysis of
      SmaI digests was used to determine chromosomal backgrounds. All strains recovered
      during the outbreak in the orthopedic ward were found to belong to a single clone
      that carried the mecA polymorph I, Tn554 type E in a macrorestriction background
      called H (clone I::E::H1), which was identified in 18 patients, and 5 health care
      personnel and from a fomite sample, and was traced to a single transfer patient
      admitted to the hospital at the beginning of the outbreak. The new clone I::E::H1
      differed only in the macrorestriction profile from the MRSA clone previously
      dominant in this hospital, known as Iberian epidemic clone I::E::A, which has
      already been identified in several Spanish and Portuguese hospitals.

PMID- 9158793
TI  - Characterization of methicillin-resistant Staphylococcus aureus isolates from
      Portuguese hospitals by multiple genotyping methods.
AB  - One hundred and eighty-three methicillin-resistant Staphylococcus aureus (MRSA)
      isolates from eight different Portuguese hospitals were genetically typed by
      random amplification of polymorphic DNA (RAPD) employing different
      oligonucleotide primers. Fourteen different RAPD genotypes were identified. A
      subset of the same strains was also characterized by pulsed-field gel
      electrophoresis (PFGE) and/or hybridization using mecA and Tn554 probes. In the
      majority of cases, the different genotyping methods have identified the same MRSA
      clones. However, PFGE combined with the DNA probes was clearly the method
      providing higher resolution. Most strains that have already been identified by
      PFGE and DNA probes as members of the widely spread Iberian clone of MRSA
      generated a common RAPD genotype. The most prevalent Iberian clone was not
      detected in a collection of MRSA from Poland that was also examined by RAPD. On
      the other hand, MRSA strains second most frequent in prevalence in the Portuguese
      and Polish collection appear to be identical by RAPD, indicating extensive
      geographic spread of this particular clone. No correlation was apparent between
      epidemic behavior and the number of protein A gene repeats in this particular
      collection of MRSA strains.

PMID- 9158794
TI  - Testing the efficacy of a molecular surveillance network: methicillin-resistant
      Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF)
      genotypes in six hospitals in the metropolitan New York City area. The BARG
      Initiative Pilot Study Group. Bacterial Antibiotic Resistance Group.
AB  - Molecular fingerprinting techniques are rapidly becoming indispensable tools for
      hospital epidemiology. On the other hand, the relative complexity and
      unfamiliarity of these techniques to most hospital diagnostic laboratories limit
      their usefulness. In an attempt to provide a solution for this dilemma, we tested
      the feasibility and efficacy of a cooperative venture in which molecular typing
      of isolates recovered from patients in six hospitals was performed at two
      microbiology research laboratories with expertise in these techniques. In a small
      preliminary study, 30 methicillin-resistant Staphylococcus aureus (MRSA) and 30
      vancomycin-resistant Enterococcus faecium (VREF) isolates were collected over a 3
      week period from six hospitals in the metropolitan New York area and transported
      to the Laboratory of Microbiology at The Rockefeller University during the summer
      months of 1994. Nineteen of the 27 confirmed MRSA isolates were closely related
      strains carrying the same mecA and the same Tn554 polymorphs in a pulsed-field
      gel electrophoresis (PFGE) background represented by closely related subtypes of
      a single pattern, indicating the wide distribution of this MRSA clone among the
      participating hospitals. Typing of the same 27 MRSA isolates was also performed
      at the Tuberculosis Center of the Public Health Research Institute and identical
      results were obtained. The 29 confirmed VREF isolates were highly heterogeneous
      and belonged to as many as 23 distinct clonal types as defined by PFGE patterns
      and probing with vanA. Characterization of the 60 isolates by these methods was
      completed in one month of full-time effort by a single experienced laboratory
      assistant guided by a doctoral-level expert in molecular fingerprinting
      techniques. The collection of samples for both MRSA and VREF was not intended to
      address epidemiological questions but to determine the feasibility of a
      multicenter study. On the basis of our preliminary findings we are encouraged
      that a larger cooperative effort is possible and with the correct sampling method
      we believe that epidemiological and surveillance studies could be accomplished
      that would provide a tracking system to assist hospitals, clinics, and chronic
      care facilities in controlling the spread of multidrug-resistant pathogens.

PMID- 9158795
TI  - Emergence of resistance to beta-lactam agents in enterobacteriaceae species with
      group I beta-lactamases in Spain.
AB  - The contribution of induction and stable derepression of chromosomal group I beta
      lactamases to beta-lactam antibiotics resistance was studied in clinical isolates
      of Enterobacteriaceae, collected from patients treated with these antibiotics.
      Multiple isolates of the same species from the same patient were characterized by
      different typing methods. Sonicated extracts of cells were assayed for
      chromosomal and plasmid-mediated beta-lactamases by isoelectric focusing and
      cloxacillin inhibition studies. The specific beta-lactamase activity, basal and
      induced with cefoxitin, was determined to differentiate strains with inducible or
      derepressed production of the enzyme. Induction of beta-lactamases was performed
      in each strain against the beta-lactams used in the therapy of each patient.
      Older penicillins resulted in a moderate to strong increase in beta-lactamase
      activity, whereas the results obtained with first-generation cephalosporins were
      species dependent. Expanded-spectrum cephalosporins were weak inducers of beta
      lactamases. Indeed, the use of cefotaxime for treatment preceded the appearance
      of strains that produced chromosomal group I beta-lactamases constitutively.
      These strains showed a remarkable reduction in sensitivity to ureidopenicillins,
      carboxipenicillins, expanded-spectrum cephalosporins, and monobactams, but not to
      carbapenems.

PMID- 9158796
TI  - In vitro susceptibility of Streptococcus pneumoniae strains to nine beta-lactam
      antibiotics and the killing kinetics of cephalosporins alone and in combination
      with vancomycin or gentamicin.
AB  - Minimum inhibitory concentrations (MICs) of a total of 68 Streptococcus (S.)
      pneumoniae strains (21 susceptible, 23 intermediate, and 24 resistant to
      penicillin) were tested for 9 beta-lactam antibiotics such as penicillin,
      cefpirome, cefotaxime, ceftriaxone, cefuroxime, ceftazidime, cefpodoxime,
      cefodizime, and amoxycillin. MICs to penicillin, cefotaxime, cefpirome, and
      ceftriaxone were also tested on Muller-Hinton blood agar supplemented with 50%
      human serum. Killing kinetics of 0.5, 2, and 4 times the MIC of cefpirome and
      cefotaxime and synergistic bactericidal activity of combinations of
      cephalosporins with vancomycin or gentamicin were investigated. The synergism
      studies were conducted with drug concentrations half of the MICs. On the basis of
      MIC50 values cefpirome, cefotaxime, ceftriaxone, and cefpodoxime were 8, 4, 2,
      and 2 times more active than penicillin, while on the basis of MIC90 values they
      were 8, 8, 4, and 2 times superior to penicillin for the penicillin-resistant S.
      pneumoniae. Cefuroxime, cefodizime, and amoxycillin showed an identical or a 2
      fold higher MIC50 or MIC90 than penicillin for the same group of isolates.
      Ceftazidime showed the lowest activity against S. pneumoniae. MIC50 and MIC90
      values for ceftriaxone increased 4-fold when human serum was added to the test
      medium. Cefpirome was the only drug with MIC50 for the penicillin-resistant S.
      pneumoniae below the new resistance breakpoint of the NCCLS (> or = 2 mg/liter),
      while these values for cefotaxime and ceftriaxone were identical to or 2-fold
      higher than the resistance breakpoint. The MIC50 and MIC90 of the other drugs
      tested exceeded the breakpoint 2 to 16 times. The combination of vancomycin with
      cefpirome or cefotaxime showed a higher killing activity to two penicillin
      resistant strains tested than 2- and 4-fold concentrations of the MICs of the two
      cephalosporins alone.

PMID- 9158797
TI  - Management of group A streptococcus pharyngitis with a second-generation rapid
      strep screen: Strep A OIA.
AB  - Empirical therapy of presumed group A streptococcus (GAS) pharyngitis leads to
      unnecessary and inappropriate use of antibiotics and pressure for emergence of
      resistant strains of common bacteria. Immunoassay technology has produced several
      rapid tests for GAS. The wide variations in diagnosis and treatment of acute
      pharyngitis are reviewed including the impact of rapid strep tests. Published
      studies comparing Strep A OIA to routine agar culture and other rapid strep
      screens are presented to assess the reliability and applicability of this novel
      assay. These data suggest that Strep A OIA may be superior to the "gold standard"
      throat culture and other rapid streptococcal antigen detection assays. Judicious
      use of Strep A OIA can result in rapid, precise diagnoses and eliminate
      unnecessary and inappropriate use of antibiotics. Careful antibiotic selection
      can reduce the pressure for emergence of resistant bacteria. This innovative,
      effective assay can contribute to a lessening of this serious clinical challenge.

PMID- 9158798
TI  - Inducible expression of the chromosomal cdiA from Citrobacter diversus NF85,
      encoding an ambler class A beta-lactamase, is under similar genetic control to
      the chromosomal ampC, encoding an ambler class C enzyme, from Citrobacter
      freundii OS60.
AB  - This study aimed to characterize the molecular basis of beta-lactamase induction
      in Citrobacter diversus. The chromosomal beta-lactamase encoding region from C.
      diversus, strain NF85, was cloned and expressed in Escherichia coli. The cloned
      region was sequenced and open-reading frames encoding a class A beta-lactamase,
      designated cdiA, and a putative LysR-type transcriptional regulator protein,
      divergently transcribed from the beta-lactamase gene and designated cdiR, were
      identified. The nucleotide sequence of the NF85 cdiA was identical to that of the
      published C. diversus ULA27 ampC sequence. A putative helix-turn-helix DNA
      binding motif was located at the N-terminus of CdiR, and homology with
      enterobacterial AmpR proteins was noted. CdiR was demonstrated to bind to the C.
      diversus cdiAR intergenic region but not to the C. freundii ampCR intergenic
      region. A putative CdiR binding motif was identified in the cdiAR intergenic
      region. The cloned cdiAR region was inducible in E. coli strains SNO3 and HfrH.
      The inducible phenotype was dependent on the E. coli ampD and ampG gene products.
      We conclude that the molecular basis of inducible cdiA expression in C. diversus
      is similar to that of C. freundii ampC.

PMID- 9158799
TI  - Molecular epidemiology of enterococci with high-level resistance to
      aminoglycosides.
AB  - DNA-based methodologies are considerably more powerful than other phenotype-based
      typing systems, providing a finer level of epidemiological discrimination,
      differentiating both closely and distantly related independent isolates that
      otherwise may appear as identical. In this study, plasmid analysis and pulsed
      field gel electrophoresis were used to compare 28 isolates of Enterococci
      (respectively 13 strains of Enterococcus faecalis and 15 strains of Enterococcus
      faecium) with high-level resistance to aminoglycosides, isolated in Catania
      (Italy). Plasmid profile analysis resolved 20 different patterns among 24 plasmid
      harboring strains; many isolates showed one or two plasmids of the same size, but
      different plasmid content. Analysis of the PFGE-based RFLP patterns after SmaI
      digestion of genomic DNA resolved 26 different clones from 28 isolates:
      particularly, it resolved two different clones from three isolates showing
      identical plasmid profiles, and it identified as a single clone two isolates
      exhibiting different plasmid profiles. Thus, on the basis of our PFGE-based RFLP
      analysis data, we concluded that all the strains included in the study were
      genetically unrelated with two exceptions.

PMID- 9158800
TI  - Multidrug-resistant Iberian epidemic clone of methicillin-resistant
      Staphylococcus aureus endemic in a hospital in northern Portugal.
AB  - Forty-two methicillin-resistant Staphylococcus aureus (MRSA) isolates collected
      during 1992-1995 at a hospital in the north of Portugal were characterized by a
      variety of genomic fingerprints. Hybridization of ClaI and SmaI restriction
      digests with the mecA- and Tn554-specific DNA probes was used to identify
      polymorphs and determine their localization in chromosomal DNA preparations, and
      pulsed-field gel electrophoretic analysis of SmaI digests was used to determine
      chromosomal backgrounds. A major clone (and its variants) carrying the mecA
      polymorph I, Tn554 type E in the PFGE background of pattern A, accounted for 85%
      of all MRSA tested in 1992-1993 and 66% in 1994-1995. This clone is closely
      related to the epidemic Iberian clone that was associated with outbreaks in Spain
      during 1989-1993 and was endemic in 1992-1993 in two hospitals in Lisbon
      (Portugal).

PMID- 9158801
TI  - Tracing the spread of methicillin-resistant Staphylococcus aureus by Southern
      blot hybridization using gene-specific probes of mec and Tn554.
AB  - In a community hospital in Brooklyn, New York, over a 3-year period, 79
      methicillin-resistant Staphylococcus aureus (MRSA) isolates from five different
      case clusters were subtyped by Southern blot hybridization with two previously
      characterized gene probes, mec and Tn554. Together, the genotyping enabled the
      hospital infection control team to differentiate simultaneous MRSA clusters in
      the surgical intensive care unit (type I:A) and the open heart unit (type II:J),
      document the spread of one strain (type I:A) between roommates, identify an
      endemic strain (type II:J) from cardiac monitors and medical personnel, and
      identify an unrelated outbreak strain (type II:NH) in the labor and delivery
      unit. On the basis of this investigation it is clear that the routine DNA
      fingerprinting of MRSA in health care facilities, to monitor their spread and
      identify cases of nosocomial infections, is an important infection control
      measure.

PMID- 9158802
TI  - Antimicrobial resistance of coagulase-negative staphylococci from a Kuwait
      hospital.
AB  - This study investigated the incidence of antimicrobial resistance in clinically
      significant coagulase-negative staphylococci at the Mubarak Al Kabeer Hospital,
      Kuwait. A total of 104 isolates of coagulase-negative staphylococci consisting of
      S. epidermidis (67), S. haemolyticus (16), S. saprophyticus (6), S. simulans (2),
      S. hominis (4), S. albus (2), S. sciuri (3), S. warneri (2), S. capitis (1), and
      S. xylosus (1) were isolated from clinical specimens over a 6-7 month period and
      tested for resistance to 22 antibacterial agents and the ability to produce
      slime. They were all susceptible to vancomycin and mupirocin but intermediate
      resistance to teicoplanin was detected in seven isolates: 83 and 47.7% were
      resistant to penicillin G and methicillin, respectively, 57% were resistant to
      gentamicin, 49.5% to erythromycin, 50.4% to tetracycline, and 52.3% to
      trimethoprim. Resistance to heavy metals and the nucleic-acid binding compound
      was also detected. More than half of S. epidermidis, S. saprophyticus, S.
      simulans, S. hominis, and all of S. haemolyticus were multiply resistant to three
      or more groups of antibiotics and there was a significant association between
      slime production and resistance to multiple antimicrobial agents in S.
      epidermidis. The results revealed a high level of resistance to commonly used
      agents.

PMID- 9158803
TI  - Detection of rifampin resistance among isolates of Mycobacterium tuberculosis
      from Mozambique.
AB  - Rifampin resistance in respiratory isolates of Mycobacterium tuberculosis from
      Mozambique was detected by screening for point mutations using polymerase chain
      reaction (PCR) and DNA sequence analysis. The target template was a 350-bp
      fragment of rpoB encoding the beta-subunit of the RNA polymerase. Of the 66
      strains studied, 38 were rifampin resistant by susceptibility testing with the
      radiometric method, 3 were intermediately resistant, and 25 were susceptible to
      rifampin. In 39 of the 41 rifampin-resistant strains, base-substitutions in the
      rpoB fragment were detected, and a total of 13 distinct mutations affecting 6
      amino acids were observed. One of these mutations (His-->Thr in amino acid 526)
      was not previously described. The isolates were also investigated by restriction
      fragment length polymorphism (RFLP) analysis using the insertion element IS6110
      as a hybridization probe. A total of 47 RFLP patterns were identified, with up to
      9 isolates having the same RFLP pattern. Strains with the same RFLP pattern
      harbored different mutations in rpoB, suggesting that acquisition of rifampin
      resistance followed the spread of a rifampin-susceptible clone. The data showed
      that rifampin resistance can be detected with a high sensitivity by DNA sequence
      analysis of this fragment of rpoB. However, a few strains with rifampin
      resistance due to factors other than base substitutions in rpoB could be missed.

PMID- 9158804
TI  - Five-year survey of cefotaxime resistance in Spain.
AB  - During 1991-1995 a Spain collaborative study group surveyed the resistance to
      cefotaxime both in community as well as in hospital isolates of bacteria. The
      isolates tested during the study period of 5 years were 813, 875, 3631, 3184, and
      3050 strains, respectively. Antimicrobial activity of cefotaxime was assayed by
      broth or agar microdilution, in accordance with criteria of the National
      Committee of Clinical Laboratory Standards (NCCLS). Cefotaxime resistance
      included 2.5% of all isolates: 2.6% Enterobacteriaceae, 1.7% Streptococcus
      pneumoniae, 0.5% Haemophilus influenzae, 0.0% Haemophilus spp., and 0.0%
      Moraxella catarrhalis. The overall incidence of resistance to cefotaxime
      decreased fro member of Enterobacteriaceae from 3.6% in 1991 to 2.5% in 1995. The
      incidence of resistance varied with the species and was highest in Enterobacter
      and in Citrobacter freundii.

PMID- 9158805
TI  - Prevalent mechanisms of resistance among common enterobacterial isolates in Greek
      hospitals.
AB  - The recent data concerning antibiotic resistance of the enterobacteria isolated
      in Greek hospitals are reviewed. A variety of mechanisms of resistance, clustered
      in most of the cases, was observed. Epidemics of plasmids were responsible for
      dissemination of third-generation cephalosporins, aminoglycosides, and
      trimethoprim resistance among Klebsiella pneumoniae and, to a lesser extent,
      Escherichia coli isolates. Stable depression of the expression of chromosomal
      cephalosporinase is the main cause of resistance to third-generation
      cephalosporins observed at high frequencies in Enterobacter spp. strains.

PMID- 9158806
TI  - In vitro activity of RP 59500 (quinupristin/dalfopristin) and ramoplanin against
      vancomycin-resistant Enterococcus faecium.
AB  - Vancomycin-resistant Enterococcus faecium (VREF) collected between July 1991 and
      February 1994 were tested in vitro against RP 59500 and ramoplanin using agar
      dilution and standard macro broth dilution procedures. Colony counts were
      determined at 0, 4, and 24 h. RP 59500 had an MIC range of < or = 0.5-8
      micrograms/ml with an MIC90 of 2 micrograms/ml and a MBC range of < or = 0.5-16
      micrograms/ml with an MBC90 of 16 micrograms/ml. Ramoplanin had an MIC range of <
      or = 0.125-1 microgram/ml with an MBC range of < or = 0.125-4 micrograms/ml. The
      MIC90 for ramoplanin was 1 microgram/ml and the MBC90 was 4 micrograms/ml for the
      tested isolates. Against these isolates of E. faecium, RP 59500 was bactericidal
      at 8x MIC, a potentially achievable level using a high drug dosage. Ramoplanin
      was bactericidal at 2x MIC.

PMID- 9158807
TI  - Cases of Lyme borreliosis resistant to conventional treatment: improved symptoms
      with cephalosporin plus specific beta-lactamase inhibition.
AB  - We present four cases of verified late Lyme borreliosis with persistent symptoms
      and positive serology despite repeated courses of high-dose intravenous
      penicillin G and/or cephalosporins (including cefoperazone). The patients were
      now treated with cefoperazone 2 g plus sulbactam 1 g bid iv for 14 days. At the
      end of treatment, patients were symptom free and have remained so for the
      following 12 months. By then, IgG against Borrelia burgdorferi had decreased. It
      is concluded that the addition of beta-lactamase inhibitors to intravenous
      treatment could be beneficial in Lyme disease refractory to conventional
      treatment.

PMID- 9158808
TI  - Ubiquitous presence of a mecA homologue in natural isolates of Staphylococcus
      sciuri.
AB  - In an effort to explore the origin and/or reservoirs of the genetic
      determinant(s) of methicillin resistance in Staphylococcus aureus, we examined
      over 200 strains representing 13 different species within the genus
      Staphylococcus for the presence of the mecA gene, using a DNA probe internal to
      this gene prepared from a methicillin-resistant strain of S. aureus. Occasional
      mecA- positive isolates were detected among several staphylococcal species. On
      the other hand, each one of the 134 isolates of Staphylococcus sciuri, a species
      considered taxonomically the most primitive among staphylococci and found
      primarily on rodents and primitive mammals, gave positive reaction with the DNA
      probe when tested under conditions of high stringency. About two thirds (99) of
      these isolates, all of which belonged to S. sciuri subspecies "sciuri," as well
      as 9 of the 11 species carnaticum isolates, showed only marginal, if any,
      resistance to methicillin (minimal inhibitory concentration of 0.75-6.0
      micrograms/ml), while most of the remaining isolates that belonged to the
      subspecies "rodentius" (13 isolates in all) expressed antibiotic resistance with
      a heterogeneous phenotype similar to those seen in many methicillin-resistance
      strains of S. aureus In SmaI digests of chromosomal DNA isolated from such
      "methicillin-resistant S. aureus-like" strains, the mecA probe hybridized with
      DNA fragments in the range of 145-180 kb, while in subspecies "sciuri" and
      carnaticum isolates the mecA hybridizing fragment was located in the SmaI
      fragment with the highest molecular size (> or = 400 kb). A DNA probe comprising
      an internal sequence to the regulatory gene mecI from Staphylococcus epidermidis
      identified the presence of sequences with low degree of homology in isolates of
      the three S. sciuri subspecies. The mecA-reacting sequences in these bacteria
      differed from mecA of S. aureus in several respects (e.g., by the absence of a
      ClaI restriction site from mecA of subspecies "sciuri" and carnaticum, and in
      some isolates of subspecies "rodentius." The uniform presence of mecA in each one
      of a large number of S. sciuri strains belonging to distinct ribotypes and
      macrorestriction patterns and recovered over a 20-year period from a wide variety
      of animal sources and geographic sites suggests that mecA may be a native genetic
      element with an as yet unidentified physiologic function in this staphylococcal
      species.

PMID- 9158809
TI  - Emergence of a methicillin-resistant Staphylococcus aureus clone related to the
      Brazilian epidemic clone III::B:A causing invasive disease among AIDS patients in
      a Brazilian hospital.
AB  - In a previous study we described the extensive geographic spread of a multidrug
      resistant methicillin-resistant Staphylococcus aureus (MRSA) clone in hospitals
      located in the southern, southeastern, and northern parts of Brazil. In this
      study we used a set of molecular markers to demonstrate the emergence of a novel
      MRSA clone distinct from but closely related to the widely spread Brazilian
      epidemic clone. The new MRSA clone caused an outbreak among acquired
      immunodeficiency syndrome patients in a Brazilian hospital specializing in
      tropical diseases and human immunodeficiency virus- and human T-cell leukemia
      virus (HLTV)-related infections.

PMID- 9158810
TI  - High incidence of multidrug-resistant Streptococcus pneumoniae in South Korea.
AB  - Streptococcus pneumoniae was isolated from patients with bacteremia, meningitis,
      pneumonia, and otitis media and used to determine susceptibility to various
      antibiotics. Of 105 isolates, 51% to 83% were resistant to 6 antibiotics (i.e.,
      the percentages of resistance to penicillin, ampicillin, cephalothin,
      chloramphenicol, tetracycline, and erythromycin were 78%, 67%, 51%, 56%, 83%, and
      58%, respectively). Also, 66 of the 105 isolates were multidrug resistant.
      Seventy-eight percent of multidrug-resistant strains were highly resistant to
      tetracycline (minimum inhibitory concentration [MIC] > or = 50 micrograms/ml),
      and 39% of multidrug-resistant strains were also highly resistant to erythromycin
      (MIC > or = 128 micrograms/ml). However, only 4% of the 105 isolates were
      resistant to cefotaxime.

PMID- 9158812
TI  - Persistence of vancomycin-resistant Enterococcus faecium gastrointestinal tract
      colonization in antibiotic-treated mice.
AB  - Colonization with vancomycin-resistant Enterococcus faecium (VREF) is strongly
      associated with previous antimicrobial therapy. The gastrointestinal (GI) tract
      appears to be the major reservoir for this organism. We used antibiotic-treated
      Swiss Webster mice to study GI tract colonization with a characterized strain of
      VREF (E. faecium 228). Mice were pretreated with antibiotics in their daily
      drinking water and inoculated with 10(9) colony-forming units (CFU) of E. faecium
      228 by oral gavage. We were able to establish persistent colonization with high
      concentrations of E. faecium 228 (> 8.0 log10 CFU/g of feces) in animals treated
      with 5 mg/ml of streptomycin plus 1 mg/ml of cefotetan. RP 59500, a streptogramin
      antibiotic with good in vitro activity against VREF, was administered orally in
      mice (n = 8) colonized with E. faecium 228. After 14 days of treatment VREF was
      undetectable in feces of all treated mice (< 3.0 CFU/g). Seven days after
      discontinuation of RP 59500, VREF was present in the feces of all animals. VREF
      isolates recovered after treatment remained susceptible to RP 59500. Attempts to
      eradicate E. faecium 228 colonization by oral administration of a vancomycin
      sensitive E. faecium strain (SF68) or Lactobacillus spp. were unsuccessful as
      long as animals continued to receive streptomycin and cefotetan. Recovery of E.
      faecium 228 from cultures of livers and gallbladders in some animals with
      persistent GI tract colonization suggests that the organisms may also colonize
      the hepatobiliary system.

PMID- 9158811
TI  - Treatment of vancomycin-resistant Enterococcus faecium infections with an
      investigational streptogramin antibiotic (quinupristin/dalfopristin): a report of
      fifteen cases.
AB  - New therapies for vancomycin-resistant Enterococcus faecium (VREF) infections are
      urgently needed. We describe the treatment of 15 patients with VREF infection
      with quinupristin/dalfopristin (RP 59500), a new injectable streptogramin
      antibiotic. Primary infections treated were bacteremia (4), urinary tract (4),
      intraabdominal (5), otitis externa (1), and meningitis (1). Minimum inhibitory
      concentrations for quinupristin/dalfopristin ranged from 0.5 microgram/ml or less
      to 2 micrograms/ml, and minimum bactericidal concentrations were greater than 64
      micrograms/ml for all VREF isolates tested. Peak serum inhibitory titers
      following infusion of quinupristin/dalfopristin ranged from 1:8 to 1:64; all
      bactericidal titers were less than 1:2. Development of resistance to
      quinupristin/dalfopristin during therapy was not observed. The only drug-related
      adverse effect noted was phlebitis in 4 patients; all had received
      quinupristin/dalfopristin by peripheral venous infusion. Three patients had
      clinical and bacteriologic cures. Relapses occurred in 5 patients with recovery
      of VREF from infected sites in post-treatment cultures. Ten patients died of
      severe underlying disease; VREF was believed to contribute directly to the death
      of only 1 patient. While evaluation of clinical efficacy was complicated by the
      severity of underlying disease in patients with VREF infection, our experience
      suggests that quinupristin/dalfopristin is a safe and potentially useful agent
      for the treatment of VREF infections.

PMID- 9158813
TI  - Molecular tracking of coagulase-negative staphylococcal isolates from catheter
      related infections.
AB  - Three molecular typing methods (pulsed-field electrophoresis, localization of the
      mecA gene, and probing the vicinity of mec) have been used for the
      characterization of 40 catheter-related isolates of coagulase-negative
      staphylococci (CNS) in 14 patients admitted to the same hospital. The 40 isolates
      yielded 14 different SmaI banding patterns and corresponding unique localizations
      of mecA, each associated with a unique ClaI mecA polymorph. In 6 of the 14
      patients the contaminated skin at the catheter entry site was the source of 4
      local infections and 2 cases of bacteremia. A contaminated hub was the origin of
      2 local infections and 4 cases of bacteremia in 6 more patients. The remaining 2
      patients had positive cultures from both skin and catheter hub. In each
      bacteremic patient, the CNS recovered from catheter-related sites (tip, skin,
      and/or hub) and the CNS recovered from blood were identical, but each of these
      matching isolates was unique to the particular patients, indicating a low rate of
      cross-infection from patient to patient. Although classical methods for typing
      CNS (e.g., biotype and antibiotype) are readily available for most hospital
      laboratories, they have limitations concerning reproducibility and discriminatory
      power. Molecular epidemiologic techniques can provide powerful support to
      traditional techniques in determining the etiologic role of CNS in the disease
      process.

PMID- 9158814
TI  - Multidrug-resistant Streptococcus pneumoniae.
AB  - Antimicrobial resistance in pneumococci is well established. Of major concern is
      the development of resistance to penicillin; however, reduced susceptibility to
      other commonly used agents such as chloramphenicol, erythromycin, and
      tetracycline has also been observed with increasing frequency. We wish to report
      the isolation of a clinical strain of Streptococcus pneumoniae with intermediate
      susceptibility to penicillin (minimum inhibitory concentration, 1 mg/L), which
      was also resistant to numerous other antimicrobial agents.

PMID- 9158815
TI  - Induction of albendazole resistance in Giardia lamblia.
AB  - Previous studies have shown that Giardia lamblia resistance to metronidazole can
      be induced in the laboratory, and treatment failures with this drug have also
      been documented. As replacement therapies, anthelmintic benzimidazoles have
      antigiardial activity with few clinical side effects. Albendazole has the
      greatest antigiardial activity of anthelmintic benzimidazoles tested and is
      effective in vivo. Although Chavez et al. failed to subculture albendazole
      exposed G. lamblia, some patient isolates have shown decreased in vitro
      sensitivity to this drug. In this study, in vitro resistance to albendazole was
      induced in G. lamblia by a method similar to that reported by Townson et al.

PMID- 9158816
TI  - Tracking the evolutionary origin of the methicillin resistance gene: cloning and
      sequencing of a homologue of mecA from a methicillin susceptible strain of
      Staphylococcus sciuri.
AB  - The gene mecA, a central genetic determinant of methicillin resistance in
      Staphylococcus aureus and coagulase-negative staphylococci of human origin, has
      an unknown extra species origin in these human pathogens. After screening
      isolates representing over 15 different species within the genus Staphylococcus
      we could identify only one--S. sciuri--in which each of over 150 independent
      isolates showed positive hybridization with a mecA-specific DNA probe isolated
      from a methicillin-resistant strain of S. aureus, (MRSA). Yet, the majority of
      these isolates showed no resistance to penicillin or methicillin. The mecA gene
      homologue was cloned and sequenced from a S. sciuri strain and the sequence of
      mecA was compared to that of the mecA of prototype strains of methicillin
      resistant S. aureus and S. epidermidis. Similarly to mecA of MRSA, the mecA
      homologue of S. sciuri was composed of a putative transglycosylase and a
      transpeptidase domain the latter showing all the conserved motifs typical of the
      active sites of the penicillin binding domain of transpeptidases. Overall
      similarity between the deduced amino acid sequences of mecA of MRSA and the mecA
      homologue of S. sciuri was 88%. On the other hand, comparison of the
      transpeptidase domain of the S. sciuri mecA to the corresponding domain alone of
      the MRSA mecA showed a similarity of 96% and an identity of 91%, while comparison
      of the putative transglycosylase domains of the two bacteria showed only a 80%
      similarity and 68% identity of amino acid sequences. Our data suggests that mecA
      of methicillin-resistant strains of staphylococci pathogenic to Man originated
      within the genus of Staphylococcus from an evolutionary relative of the mecA
      homologue that we have identified in S. sciuri and which may perform a normal
      physiological function in this bacterium unrelated to beta-lactam resistance.

PMID- 9158817
TI  - Infrared analysis in clinical chemistry: its use in the laboratory and in non
      invasive near patient testing.
AB  - Laboratory based NIR analysers have been available for some time. The recent
      development of more portable equipment such as the commercially available Futrex
      9000 NIR transmittance blood chemistry analyser, which can be used to analyse
      relatively opaque samples for a mixture of components, shows promise but requires
      further evaluation for routine clinical use. NIR equipment for general use has
      only recently become available and is therefore relatively expensive. However, as
      the development of new applications occurs the instrumentation will become more
      widely used, which will inevitably result in reduced capital cost. The advantages
      of NIR systems are speed, portability, lack of consumables, dry chemistry, non
      invasive, modest running costs, virtually no moving parts and almost infinite
      applications in clinical biochemical analysis. It is likely that the first
      applications of NIR will be where there is a requirement for multiple assays such
      as glucose, urea and bilirubin and where sample size is a limitation. Thus non
      invasive near patient testing may become common in the future in settings such as
      neonatal units, renal units, diabetic clinics and intensive care units.

PMID- 9158818
TI  - Evidence for the low dose dexamethasone suppression test to screen for Cushing's
      syndrome--recommendations for a protocol for biochemistry laboratories.

PMID- 9158819
TI  - Molecular basis, clinical consequences and diagnosis of alpha-1 antitrypsin
      deficiency.
AB  - (1) Deficiency of alpha AT is one of the most common hereditary diseases
      affecting Caucasians in Europe. The alpha 1AT protein is extremely pleomorphic,
      and around 90 variants due to mutations have been recognized. The prime functions
      of alpha 1AT is to inhibit neutrophil elastase, and a proportion of individuals
      who are deficient in alpha 1AT develop emphysema. The most common deficiency
      variant (Z) is also associated with liver disease. The main site of alpha 1AT
      synthesis is in the liver. Not all deficient individuals are affected by lung or
      liver disease, however, so that other factors (genetic and environmental) are
      clearly important. (2) Investigation of alpha 1AT status is essential in any
      child or adult presenting with chronic liver disease. The genetic cause cannot be
      identified clinically or by any other laboratory investigation. The diagnosis
      carries important prognostic consequences and is important for other family
      members. Patients with emphysema should have their Pi type determined, especially
      if they are under the age of 50, have never smoked or there is a suggestive
      family history. Asymptomatic individuals who are homozygous type Z should be
      referred to a chest physician for a clinical and radiological assessment together
      with lung function tests. (3) Several laboratory tests are available to detect
      alpha 1AT deficiency, and the choice of test(s) will depend on circumstances.
      Quantitation of the serum protein is simple and cheap. Because alpha 1AT is an
      acute phase protein, however, quantitation used in isolation may give false
      negative results which are clearly unacceptable, particularly in association with
      paediatric liver disease. Phenotyping by isoelectric focusing requires some
      experience in distinguishing SZ and ZZ phenotypes, and phenotyping should ideally
      be used in conjunction with quantitation because heterozygous null phenotypes may
      appear identical to homozygous normal phenotypes. (4) Prenatal diagnosis is
      usually performed by DNA analysis of CVS samples obtained at 11-13 weeks. Because
      of the risk that CVS samples might be contaminated by maternal tissue, assays
      which are less likely to detect minor contaminants are preferable. At present,
      use of DNA tests is confined to prenatal diagnosis, but the availability of
      simple tests and the possibility of unequivocal identification of S and Z alleles
      means that these tests are likely to find greater use in the near future.

PMID- 9158820
TI  - Microalbuminuria in type 2 diabetic patients: a prospective follow-up study.
AB  - We have studied 46 patients, 30 men and 16 women, with type 2 (non-insulin
      dependent) diabetes in a follow-up period of 6-52 months (mean 30 months). The
      patients were consecutively entered in the study from the out-patient diabetic
      clinic. None had urinary tract infections nor proteinuria at entry.
      Investigations were done every 3 months during the first year and after that
      every 6 months. At entry 16 patients (35%) had microalbuminuria and a further 16
      patients developed microalbuminuria and 16 proteinuria. The systolic blood
      pressure was higher in men with microalbuminuria compared to men without
      microalbuminuria. The glomerular filtration rate decreased with time for patients
      with microalbuminuria without change in plasma creatinine. The C-peptide
      concentration was higher in the hypertensive patients compared to non
      hypertensive and the same was found for the triglyceride concentration. During
      the observation period the various complications increased in frequency
      (retinopathy, cardiomyopathy, neuropathy, angiopathy and hypertension) without
      significant relation to the presence of microalbuminuria or proteinuria. During
      the observation period nine patients died mainly due to cardiovascular events.

PMID- 9158821
TI  - Macroprolactinaemia: contribution to hyperprolactinaemia in a district general
      hospital and evaluation of a screening test based on precipitation with
      polyethylene glycol.
AB  - For a period of 12 months all samples submitted for serum prolactin (PRL) assay
      and with PRL > 700 mU/L were examined by gel filtration chromatography. In 17
      (25%) of 69 samples we found macroprolactin. The Delfia and Immuno 1 immunoassay
      systems gave similar PRL results with samples containing macroprolactin whereas
      the ACS 180 system gave lower results. With the Delfia and Immuno 1 systems
      samples containing substantial quantities of macroprolactin showed low recovery
      of PRL after precipitation with polyethylene glycol 6000 (PEG 6000) and this
      technique can be used as a screening test for macroprolactinaemia. We conclude
      that macroprolactinaemia is a common phenomenon and, in assays which detect this
      species, is a common cause of hyperprolactinaemia. Macroprolactinaemia may
      contribute to the difficulty in establishing an upper limit of the reference
      range for serum PRL. In our experience, patients with macroprolactinaemia do not
      exhibit features of the hyperprolactinaemia syndrome and it is important to
      recognize macroprolactin as the cause of hyperprolactinaemia to avoid unnecessary
      investigation and treatment.

PMID- 9158822
TI  - Hyperamylasaemia in asymptomatic HIV patients.
AB  - We studied serum amylase and its isoenzymes prospectively in 163 consecutive
      asymptomatic patients, 149 men and 14 women, infected with HIV and attending an
      HIV out-patient clinic. Six patients were receiving dideoxyinosine (DDI), a drug
      known to cause pancreatitis. No patient, however, had clinical signs suggestive
      of pancreatitis. Serum total amylase was increased in 39 of 163 patients (24%),
      in 11 of whom (28%), this was due to increased pancreatic (P) isoamylase alone,
      in 17 (42%) it was due to salivary (S) type alone and in six (17%) it was due to
      increase of both P and S fractions. In five patients (13%), macroamylase was
      detected. Pancreatic amylase was elevated in four of the six patients on DDI. The
      remaining two had macroamylase. Our results show that asymptomatic
      hyperamylasaemia is a common finding in HIV patients and that it appears to be
      heterogenous, i.e. elevation may be due to increase in P or S, both enzyme
      fractions or macroamylase. The high incidence of macroamylasaemia in HIV patients
      was an unexpected finding.

PMID- 9158823
TI  - One-step enzyme-linked immunosorbent assay (ELISA) for plasma fatty acid-binding
      protein.
AB  - To allow a more rapid determination of heart-type fatty acid-binding protein
      (FABP) concentration in plasma a direct non-competitive (sandwich-type) ELISA was
      developed which uses high-affinity monoclonal antibodies to FABP. Total
      performance time of the one-step immunoassay is 45 min. The standard curve was
      linear between 0.2-6 micrograms/L, and the within-run and between-run
      coefficients of variations were below 6 and 11%, respectively. The serum FABP
      concentration measured in 79 healthy individuals was 1.6 (0.8) [mean (SD), range
      0.3-5.0] micrograms/L. The assay can be used for rapid plasma or serum FABP
      measurement in the early diagnosis of acute myocardial infarction.

PMID- 9158824
TI  - Effect of simvastatin therapy on cell membrane cholesterol content and membrane
      function as assessed by polymorphonuclear cell NADPH oxidase activity.
AB  - Cell membrane cholesterol is an important determinant of membrane fluidity.
      Changes in fluidity have important consequences for membrane function. Treatment
      of hypercholesterolaemia could therefore affect membrane function by reducing
      cell membrane cholesterol levels. The aim of this study was to determine whether
      treatment with simvastatin affects membrane cholesterol and the activity of the
      polymorphonuclear cell membrane enzyme NADPH oxidase. Blood was obtained from 12
      hypercholesterolaemic patients before, and 6 weeks after, treatment with
      simvastatin, and from 20 normolipidaemic subjects. Cell cholesterol was in the
      unesterified from indicating that it was membrane-associated. Pre-treatment mean
      cell cholesterol concentration in the hyperlipidaemics was higher (P < 0.05) than
      in the normolipidaemics [4.19 fmol/cell, 95% confidence interval (CI) 3.38-5.05
      versus 3.10 fmol/cell, 95% CI 2.58-3.61]. There was a strong correlation between
      cell cholesterol content and NADPH oxidase lag phase (R(s) = 0.76, P < 0.01).
      Cell cholesterol fell to 3.52 fmol/cell (95% CI 2.77-4.28, P < 0.05) following
      treatment and there was a correlation (R(s) = 0.61, P < 0.05) between the
      reductions in cell cholesterol and lag phase.

PMID- 9158825
TI  - Variation in detection of VEGF in maternal serum by immunoassay and the possible
      influence of binding proteins.
AB  - Using radioimmunoassay (RIA) and a polyclonal antibody we have shown that
      maternal serum vascular endothelial growth factor (VEGF) is elevated during
      pregnancy. In contrast, a commercial VEGF ELISA utilizing a sandwich two-site
      immunoassay was unable to detect VEGF in 19 of the 20 maternal serum samples
      analysed. In addition, the recovery of exogenous VEGF added to the pregnancy
      samples was low or not recordable with the ELISA. Using RIA, 82-101% of the added
      VEGF was recovered. These differing results could be explained by the formation
      of VEGF-protein complexes that are detectable using RIA but undetectable with the
      ELISA. Our data imply that there is a substantial increase in circulating VEGF
      binding proteins during pregnancy. The increase in VEGF and its binding proteins
      during pregnancy may reflect important physiological events in the mother and
      feto-placental unit.

PMID- 9158826
TI  - Improving the quality of near-patient blood glucose measurement.
AB  - The quality of near-patient blood glucose measurement was audited in our
      hospitals in 1990, when a diversity of glucose meters were in use, by sending
      three samples of unknown (to the meter user) concentration to each user and
      collecting and analysing the results produced. The overall performance was
      unsatisfactory with a mean coefficient of variation (CV) of 23.5%. A scheme
      involving training, quality control and external quality assurance was introduced
      in 1993 based on the Bayer Glucometer II meter. This meter was used exclusively
      throughout our hospitals. Data from the quality assurance scheme showed that the
      overall CV fell initially to 14-16% and then settled at about 10-12% for the
      following 2 years. Unacceptable results (those more than two standard deviations
      from the mean) were 8-12% of the total. A new meter was introduced in 1995 (the
      Bayer Glucometer 4) which had the advantages of 'no-wipe' and automatic timing
      technology and in the subsequent year overall CV fell to 5-6% and has remained at
      this level. The frequency of unacceptable results fell to 5-7%. The improved
      precision figures encouraged us to change criteria for acceptability to mean +/-
      15%. Using these criteria the level of unacceptable results is now 1-2%. This
      study shows that introducing training, quality control procedures, a quality
      assurance scheme and improved meter technology all backed by laboratory expertise
      can produce significant improvement in the quality of near patient blood glucose
      measurement.

PMID- 9158827
TI  - The use of a Hemocue blood glucose analyser in a neonatal unit.
AB  - Near patient testing for glucose is now a widely accepted procedure in hospital
      wards and clinics. However, in a neonatal ward where the detection of
      hypoglycaemia rather than hyperglycaemia is of paramount importance, it is more
      difficult to find a suitable glucose monitoring instrument. We compared two
      Hemocue blood glucose analysers (Hemocue Ltd) in our special care baby unit
      (SCBU) with the laboratory procedures and found that the Hemocue may overestimate
      the glucose by as much as 2.5 mmol/L. In addition, Hemocue analysers are costly
      to run. We feel these analysers may be more useful in a general ward rather than
      in a SCBU.

PMID- 9158828
TI  - Novel instrumentation for real-time monitoring using miniaturized flow systems
      with integrated biosensors.
AB  - A prototype miniaturized Total Chemical Analysis System (muTAS) has been
      developed and applied to on-line monitoring of glucose and lactate in the core
      blood of anaesthetized dogs. The system consists of a highly efficient
      microdialysis sampling interface sited in a small-scale extracorporeal shunt
      circuit ('MiniShunt'), a silicon machined microflow manifold and integrated
      biosensor array for glucose and lactate detection with associated computer
      software for analytical process control. During in-vivo testing the device
      allowed real-time on-screen monitoring of glucose and lactate with system
      response times of less than 5 min, made possible by the small dead volume of the
      microflow system. On-line glucose and lactate measurements were made in the basal
      state as well as during intravenous infusion of glucose or lactate. The prototype
      muTAS is currently suitable for trend monitoring but refinements are necessary
      before application of the system for determination of individual lactate values.

PMID- 9158830
TI  - Atypicality revisited: further data on the effectiveness of the Mahalanobis
      distance in Down's syndrome screening.
AB  - Further data suggesting that assessment of atypicality may be a valuable addition
      to Down's syndrome screening is presented, based on results from 1521 unaffected
      pregnancies and 190 chromosomally abnormal pregnancies. For a 1% increase in
      false positive rates (over the Down's screening-related false positives), it is
      estimated that the detection of non-trisomy 21 abnormalities may be enhanced by
      approximately 40%. These false positive and detection rates are similar to
      previous reports for specific trisomy 18 screens. Further work is necessary to
      prove whether a specific trisomy 18 screen, or an atypicality screen is
      preferable.

PMID- 9158829
TI  - Observations on the relationships between plasma free fatty acids, ketones and
      bicarbonate in acute hyperglycaemia.
AB  - Some of the initial biochemical findings, obtained from 141 randomly-selected
      cases of acute hyperglycaemia (admission plasma glucose > 20 mmol/L) were
      examined. When viewed in terms of their initial plasma bicarbonate concentration,
      three groups were identifiable. Plasma concentrations of free fatty acids (FFA),
      acetone and the sum of 3-hydroxybutyrate (3OHB) and lactate were different
      between these groups. However, there were no differences in plasma glucose or
      lactate concentrations. It was further observed that the relationship between the
      plasma FFA/albumin molar ratio, and ketone concentration could be described by a
      rectangular hyperbola, and the initial anion gap was linearly related to the sum
      of the 3OHB and lactate concentrations.

PMID- 9158831
TI  - A modified sodium dodecyl sulphate-agarose gel/immunoblotting method for
      apolipoprotein(a) phenotyping using alkaline phosphatase-linked chemiluminescent
      detection.

PMID- 9158832
TI  - Intra-individual variation in serum type I procollagen carboxy-terminal
      propeptide and type I collagen carboxy-terminal cross-linked telopeptide
      concentrations.

PMID- 9158833
TI  - Method comparison: evaluation of least squares, Deming and Passing/Bablok
      regression procedures using computer simulation.

PMID- 9158834
TI  - A case of heterozygous familial hypercholesterolaemia who developed exclusive
      peripheral vascular disease.

PMID- 9158835
TI  - Pseudohyponatraemia secondary to hypercholesterolaemia.

PMID- 9158836
TI  - Origins of the sex difference in human urinary free cortisol excretion.

PMID- 9158837
TI  - The use of biochemical markers in the diagnosis and management of MI.

PMID- 9158838
TI  - Effects of early disease on later growth, and early growth on later disease, in
      Khartoum infants.
AB  - Longitudinal data of monthly length and weight measurements, and fortnightly
      infectious disease records of 167 infants in Khartoum townships, have been
      examined to determine: (1) whether disease experience in the first 6 months of
      life is related to growth in the second 6 months and (2) whether growth in the
      first period is related to disease experience in the second. Using regression
      techniques to allow for disease measure correlations in the two periods and other
      environmental factors that are associated with growth and disease, it is
      concluded that both length and especially weight growth are affected adversely by
      previous illness. On the other hand there is almost no evidence that early growth
      is associated with later disease susceptibility.

PMID- 9158839
TI  - Gradients of HLA diversity in South American Indians.
AB  - Information concerning the HLA-A and -B loci was considered in relation to 3796
      Amerindians living in 39 places in South America, data related to HLA-C being
      based on a smaller subset of 2989 persons distributed among 33 localities.
      Synthetic gene frequency maps were then constructed using principal-components
      analysis. Clearly significant longitudinal (principal component 1) and
      latitudinal (principal components 1, 2, and 3) clines were observed, most
      probably indicating ancient migration routes.

PMID- 9158840
TI  - The validity of body mass index for the assessment of adiposity in children with
      disease states.
AB  - Recently published standards for body mass index (BMI) based on population
      studies of height and weight in healthy British children allow an easy but
      indirect assessment of adiposity in healthy children. However, assessment of
      adiposity based on standards derived from reference populations may not be
      appropriate for use in subjects with disease states associated with abnormalities
      of growth and body composition. This hypothesis was tested by comparison between
      BMI standard deviation scores (SDS) and more direct measures of body fat derived
      from dual-energy X-ray absorptiometry (DEXA) and skinfold thickness in groups of
      children, receiving growth hormone, with inflammatory bowel disease, previously
      treated for malignancy, and healthy controls. Excess adiposity was defined as a
      body fat greater than the 85th percentile and was compared to a BMI SDS of +1.0.
      Overall the sensitivity and specificity for a BMI SDS of +1.0 to correctly
      identify individuals as having excess adiposity was 66% and 94%, respectively,
      when body fat was measured by DEXA, and 50% and 100% when estimated from skinfold
      measurements, respectively. There were no significant differences in these
      statistics whether applied to the individual disease groups or to healthy
      controls. These findings suggest that BMI under-predicts the prevalence of excess
      adiposity in children with disease states but surprisingly to no greater degree
      than that seen in healthy subjects.

PMID- 9158841
TI  - mtDNA analysis in ancient Nubians supports the existence of gene flow between sub
      Sahara and North Africa in the Nile Valley.
AB  - The Hpal (np3,592) mitochondrial DNA marker is a selectively neutral mutation
      that is very common in sub-Saharan Africa and is almost absent in North African
      and European populations. It has been screened in a Meroitic sample from ancient
      Nubia through PCR amplification and posterior enzyme digestion, to evaluate the
      sub-Saharan genetic influences in this population. From 29 individuals analysed,
      only 15 yield positive amplifications, four of them (26.7%) displaying the sub
      Saharan African marker. Hpa 1 (np3,592) marker is present in the sub-Saharan
      populations at a frequency of 68.7 on average. Thus, the frequency of genes from
      this area in the Merotic Nubian population can be estimated at around 39% (with a
      confidence interval from 22% to 55%). The frequency obtained fits in a south
      north decreasing gradient of Hpa I (np3,592) along the African continent. Results
      suggest that morphological changes observed historically in the Nubian
      populations are more likely to be due to the existence of south-north gene flow
      through the Nile Valley than to in-situ evolution.

PMID- 9158842
TI  - Modelling the associations of BMI physical activity and diet with arterial blood
      pressure: some results from the Allied Dunbar National Fitness Survey.
AB  - In order to identify risk factors (e.g. physical inactivity, dietary composition)
      associated with blood pressure within a given population, it is necessary to
      adjust for differences in known associations (e.g. age, body weight) using a
      method such as the analysis of covariance. However, the blood pressure results
      from the Allied Dunbar National Fitness Survey (ADNFS) were found to be non
      linear with age, positively skewed (with heteroscedastic errors) and therefore
      non-normally distributed. Hence, before valid inferences can be drawn from such
      data, there is a clear need to formulate an appropriate model for blood pressure
      that will overcome these undesirable characteristics. A multiplicative model
      (with allometric body size components) was proposed and fitted to the ADNFS blood
      pressure results. After a logarithmic transformation the parsimonious solution
      was able to confirm the association with BMI, the non-linear changes with age,
      and overcome the heteroscedastic and positively skewed errors, i.e. the residuals
      from the fitted log-linear models for both systolic and diastolic blood pressure
      were symmetric and normally distributed. Other factors were found to make a
      significant additional contribution to the prediction of blood pressure.
      Cyclists, participants in vigorous physical activity and those subjects who
      consumed more fresh fruit, rice or pasta, and wine were found to have
      significantly lower mean levels of blood pressure. Indeed, the gap in blood
      pressure between participants and non-participants in vigorous physical activity
      increased further with age. However, subjects who drank more beer tended to have
      significantly higher mean levels of blood pressure. Thus by developing an
      appropriate model for arterial blood pressure, some well known, and some less
      well known, associations with arterial blood pressure have been identified. The
      results suggest that physical activity and other lifestyle factors may protect
      against hypertension.

PMID- 9158843
TI  - D1S80 locus variability in South American Indians.
AB  - We have studied the hypervariable D1S80 locus in 185 individuals from five South
      American Indian tribes, integrating these results with previous investigations.
      Three alleles (*18, *24 and *30) were common to all tribes, but their frequencies
      varied between northern and southern populations. Brazilian tribes have a high
      frequency of *30 (average 35%) while in Argentinian and Chilean Indian
      populations this allele is present, on average, in 7% of the chromosomes only.
      Allele *24, the most common in other ethnic groups, was observed in 10% and 25%
      of northern and southern Amerindians respectively. Genetic distance and
      dendrogram analyses placed the Argentinian and Chilean tribes closer to Brazilian
      Caucasians, suggesting non-Indian admixture among them.

PMID- 9158844
TI  - Skeletal maturity of the hand and wrist of healthy Argentinian children aged 4-12
      years, assessed by the TWII method.
AB  - One previously trained observer assessed skeletal maturity in a representative
      sample of 388 and 387 healthy girls and boys respectively from La Plata city, a
      predominantly university and administrative urban centre in Argentina. The
      staging system used was TWII and the scores were calculated from three sources:
      British, Spanish and Italian standards. Our sample showed a marked advancement in
      bone age with regard to chronological age when using British standards and, to a
      lesser extent, when applying the Spanish standards. Local mean bone ages were
      very similar to chronological ages when the Italian scores were used. Second
      degree polynomials were adjusted to log10 scores for boys and girls, in order to
      obtain local values for bone age (BA) transformations. The same staging system
      should be used in clinical work in Argentina, with the corresponding changes in
      BA transformatons. A marked advancement of carpal BAs with regard to RUS BAs was
      found, from age 5 onwards, in both sexes. Mean differences and SD of RUS-minus
      carpal BA were 1.28, SD 1.08 and 1.18, SD 1.09 years for girls and boys
      respectively. These differences have not been described before, and require
      further investigation.

PMID- 9158845
TI  - "Try it; it's good and it's good for you": effects of taste and nutrition
      information on willingness to try novel foods.
AB  - In an attempt to understand the effects of information on willingness to taste
      foods, we presented college students with a variety of familiar and novel foods
      of animal and vegetable origin. Participants received one of four types of
      information about the foods: none, they tasted good, they were high in vitamins,
      or they were high in vitamins and might soon be available in the college
      cafeteria. The information manipulation had no effect on willingness to taste
      familiar foods. Willingness to taste novel non-animal foods was increased by both
      taste and vitamin-plus-availability information, while willingness to taste
      animal foods was not affected by information. Willingness to taste novel foods
      was also predicted by a measure of trait neophobia. The results suggest that (a)
      emotional reactions to animal foods may block information effects, and (b)
      nutrition information is more effective in a context where the food is believed
      to be available.

PMID- 9158846
TI  - Food cravings in young and elderly adults.
AB  - Fifty young-adult and 48 elderly Ss participated in a structured interview study
      on food cravings (defined as an intense desire or longing to eat a particular
      food). Elderly Ss were less likely than young Ss to report cravings and reported
      craving a smaller number of different foods. In contrast to a number of other
      researchers, we found a relationship between dietary restrictions and cravings.
      Types of food craved differed by gender and age. Women reported significantly
      more cravings for chocolate and for sweets than did men. However, craving for
      sweets declined with age among women. Cravings were not evenly distributed
      throughout the day, but tended to occur in the late afternoon and early evening.

PMID- 9158847
TI  - Similarities and differences in affective and cognitive origins of food likings
      and dislikes.
AB  - In a field study, 355 French-Canadian adults (Caucasians; 119 men, 236 women;
      average age of 40) freely stated the food item they liked and disliked the most,
      the reasons for their attitude and the context of their last consumption of these
      two food items. Content analysis revealed that the origins of food likes and
      dislikes are at the same time very similar and very different. They are similar
      in terms of the overwhelming influence of affective factors, in particular
      sensory experience, in the formation of both positive and negative attitudes
      toward food. Similarity between origins of food likes and dislikes in the same
      subjects is higher when they are from affective sources than when they are from
      cognitive sources. Food likes and dislikes are also similar in terms of the high
      salience of the social dimension in subjects' memories of consumption contexts.
      Results also show that food likes and dislikes also differ in many ways. Subjects
      can more easily elicit attitude bases and consumption contexts for food likes
      than they do for food dislikes. Beside taste as their common and most frequent
      base, results show that dislikes originate from more specific (e.g. texture,
      smell, appearance) and more intense sensory experiences than likes. Further,
      physiological consequences that contribute to food likes and dislikes are not the
      same: likes originate from positive nutritional value whereas dislikes follow
      from negative physiological responses, in particular nausea. Also, specific
      factors contribute uniquely to likes and dislikes. Functional aspects (e.g.
      flexibility, preparation) were the second most important reasons for food likes
      while having almost no influence on dislikes. In contrast, food symbolism was the
      third most important reason for food dislikes with almost no effect on food
      likes.

PMID- 9158848
TI  - Social class differences in women's fat and fibre consumption: a cross-national
      study.
AB  - This study focuses on social class variation in the intake of fat and fibre in
      Maastricht, Liege and Aachen, based on food frequency questionnaires of 849 women
      from nuclear families with schoolgoing children. In Maastricht and Liege higher
      middle class women consumed less fat than working class women, while in Aachen no
      class difference was apparent. The intake of fibre was highest among the higher
      middle class women, although this tendency was not significant in Aachen.
      Analysis of food groups that contribute to the intake of fat and fibre revealed
      that not all food groups showed this pattern. Higher-middle class women consumed
      less bread, less potatoes and more cheese than working class women. Moreover,
      they chose more often high-fat cheese and fats. Yet, working class women consumed
      more meat, milk and fats, and less grain, fruit and vegetables. In general,
      social class variations in fat and fibre intake were uniform across the cities,
      although in Aachen class differences were small or absent. In conclusion, these
      results suggest that the diet of higher-middle class women is more in accordance
      with the dietary recommendations regarding fat and fibre than the diet of working
      class women.

PMID- 9158849
TI  - Hyperphagia in dementia: 1. The use of an objective and reliable method for
      measuring hyperphagia in people with dementia.
AB  - Up to one third of dementia sufferers eat an increased quantity of food, compared
      with their premorbid intake, at some stage during the dementia. A proportion of
      these eat extraordinarily large quantities if food intake is not restricted. In
      order to investigate this phenomenon in detail, a reliable and standardized
      method of quantifying the degree of hyperphagia is required. We report the
      development of such a method. Twenty-six people with dementia, who were reported
      by their carers to be hyperphagic, were compared with 14 matched non-hyperphagic
      controls with dementia and 14 matched normal elderly. Subjects were offered two
      standardized meals, under specified conditions, ad libitum. One meal consisted of
      a single food, the other of a mixture of foods. The total energy intake provided
      a reliable measure of the degree of hyperphagia. The single food meal was more
      reliable but the mixed meal was a more sensitive measure of the hyperphagia.

PMID- 9158850
TI  - Hyperphagia in dementia: 2. Food choices and their macronutrient contents in
      hyperphagia, dementia and ageing.
AB  - Up to one third of dementia sufferers eat an increased quantity of food compared
      with their premorbid intake, at some stage during the dementia. In addition, over
      half of people with dementia are reported, by their carers, to show a marked
      change in food choice, particularly an increased liking for sweet food. The
      macronutrient content of foods chosen and the ratio of sweet to savoury foods
      were investigated experimentally using a standardized mixed meal. Three subject
      groups were studied: 17 people with dementia who were reported by their carers to
      overeat and who ate excessively under experimental conditions; 14 people with
      dementia who ate a normal amount; and, normal, non-demented controls (18 under 50
      years old and 14 over 50 years old). The results showed that the normal elderly
      people chose a lower proportion of high-protein food than the young. The
      proportion of protein eaten was lower in people with dementia than in age-matched
      controls and was even lower in the hyperphagic dementia group. The proportion of
      sweet food eaten was higher in people with dementia and even higher in people
      with dementia who were hyperphagic. Various mechanisms to account for the results
      are discussed.

PMID- 9158851
TI  - Hard work does not result in a decrease in meal quality: the case of a Japanese
      farming village.
AB  - Historically, when Japanese farmers engaged in hard labor, they were likely to
      increase their carbohydrate intake without increasing intake of other nutrients.
      After Japan's economic growth started in the 1960s, however, many kinds of food
      became available and affordable. We investigated whether farmers today have
      increased the nutrients in their diet in proper proportion to energy expenditures
      when they are engaged in farming work by comparing the quantity and quality of
      meals between farmers and other villagers within a small area of a farming
      village. The quantity of energy and other nutrients increased with farming work,
      but the amounts of each nutrient per unit of energy did not decrease with the
      increase in energy intake. The intake of each nutrient relative to the
      recommended dietary allowance for energy and each nutrient did not decrease with
      farming work either. It was concluded that the quality of meals of farmers does
      not decrease with the increasing energy intake for farming work when many kinds
      of food are available and affordable.

PMID- 9158852
TI  - Biocompatibility of mannuronic acid-rich alginates.
AB  - Highly purified algin preparations free of adverse contaminants with endotoxins
      and other mitogens recently became available by a new purification process (Klock
      et al., Appl. Microbiol. Biotechnol., 1994, 40, 638-643). An advantage of this
      purification protocol is that it can be applied to alginates with various ratios
      of mannuronic acid to guluronic acid. High mannuronic acid alginate capsules are
      of particular practical interest for cell transplantation and for biohybrid
      organs, because mannuronate-rich alginates are usually less viscous, allowing one
      to make gels with a higher alginate content. This will increase their stability
      and reduce the diffusion permeability and could therefore protect immobilized
      cells more efficiently against the host immune system. Here we report the
      biocompatibility of purified, mannuronic acid-rich alginate (68% mannuronate
      residues) in a series of in vitro, as well as in vivo, assays. In contrast to raw
      alginate extracts, the purified product showed no mitogenic activity towards
      murine lymphocytes in vitro. Its endotoxin content was reduced to the level of
      the solvent. Animal studies with these new, purified algin formulations revealed
      the absence of a mitogen-induced foreign body reaction, even when the purified
      material (after cross-linking with Ba2+ ions) is implanted into animal models
      with elevated macrophage activity (diabetes-prone BB/OK rat). Thus, alginate
      capsules with high mannuronic acid content become available for applications such
      as implantation. In addition to the utilization as implantable cell reactors in
      therapy and biotechnology, these purified algins have broad application potential
      as ocular fillings, tissue replacements, microencapsulated growth factors and/or
      interleukins or slow-release dosage forms of antibodies, surface coatings of
      sensors and other invasive medical devices, and in encapsulation of genetically
      engineered cells for gene therapy.

PMID- 9158853
TI  - Impulse response of a dental implant in bone by numerical analysis.
AB  - The osseointegration process of titanium dental implants in bone has been
      simulated previously using natural frequency and impulse excitation. However, the
      impulse strength was arbitrarily chosen and may not have yielded the correct
      frequencies and displacements to be compared with those measured in a clinical
      situation. In this work the range of impulse excitation strengths applied to a
      dental implant osseointegrated in bone and the corresponding response have been
      examined using the finite element method. Both conditions of a dental pin only
      and a dental pin with attached cantilever integrated in the mandible have been
      examined. The dynamic analysis indicated that the frequency and displacement
      responses are indeed sensitive to impulse duration and direction but independent
      of impulse load. The analysis summarizes the proper impulse excitation values for
      a correct interpretation of clinically measured frequency response data.

PMID- 9158854
TI  - Influence of additives on the water uptake of hydrosilanized silicone rubbers.
AB  - Water uptake characteristics of a silicone polymer containing additives of
      varying solubility have been investigated. A hydrophobic silica, a sparingly
      soluble agent and a soluble catalyst were added to a stoichiometrically balanced
      hydrosilanized silicone polymer (the inherent absorption of which was 0.09 wt%).
      The diffusion coefficients for desorption of all materials were of the order 10(
      6) cm2s-1, whereas the diffusion coefficients for absorption showed a decrease
      with increasing hydrophilicity and solubility of the additive. The greater the
      solubility of the additive, the more prolonged the uptake and the greater the
      deviation from classic diffusion theory.

PMID- 9158855
TI  - Influence of gamma-irradiation sterilization and temperature on the fracture
      toughness of ultra-high-molecular-weight polyethylene.
AB  - Surface damage of the tibial plateau components of knee prostheses made from
      medical grade ultra-high-molecular-weight polyethylene (UHMW-PE) has been
      attributed to delamination wear caused by a fatigue fracture mechanism. It has
      been proposed that factors such as component design and method of sterilization
      contribute to such failure mechanisms. Understanding the fracture behaviour of
      UHMW-PE is therefore critical in optimizing the in vivo life-span of total joint
      components. The elastic-plastic fracture toughness parameter J was consequently
      determined for a commercial UHMW-PE at ambient and body temperatures, before and
      after gamma-irradiation sterilization in air at a minimum dose of 29 kGy. Both
      ductile stability theory and experimental data suggest that cracks propagate in a
      stable manner, although stability is affected by the sterilization process.
      Sterilization with gamma-irradiation results in a loss in fracture toughness JIc
      of 50% and a decrease in tearing modulus (Tm) of 30%. This dramatic reduction
      could result in a 50% decrease in the residual strength of the components,
      maximum permissible crack size under service loading and service life (assuming
      flaws such as fusion defects exist). The time required for a crack to grow from
      its original size to the maximum permissible size could be decreased by 30%,
      resulting in earlier failure. In terms of the design of joint replacement
      components the critical factor to envisage is the design stress level, which
      should be halved to account for the irradiation process. A scanning electron
      microscope study reveals that the material fails in layers parallel to the
      fracture surface.

PMID- 9158856
TI  - Hydrolysis and phase transition of alpha-tricalcium phosphate.
AB  - Increasing attention has been paid in recent years to alpha-tricalcium phosphate
      (alpha-TCP), which is used as the main constituent of calcium phosphate bioactive
      bone cements and biphasic calcium phosphate ceramics. Its hydrolysis and
      conversion into apatite phase may play an important role in new bone formation in
      vivo. In this experiment, alpha-TCP powder was made and immersed in deionized
      water. The morphology change and phase composition were analysed before and after
      immersion. Based on the results of hydrolysis, a formula for the converted
      apatite-TCP phase containing lattice water was put forward and a partial
      structural model along the hydroxyl column was proposed.

PMID- 9158857
TI  - Characterization of calcium phosphates precipitated from simulated body fluid of
      different buffering capacities.
AB  - The purpose of this experiment was to study the properties of calcium phosphate
      precipitated from simulated body fluids (SBFs) with different buffering
      capacities. The Ca/P molar ratios of the precipitates were determined and the
      microstructure of a sintered precipitate was studied. The results indicate that
      the pH of the SBF increases during calcium phosphate precipitations, which
      affects the Ca/P molar ratios and chemical compositions of these precipitates. A
      precipitate with a Ca/P molar ratio close to the stoichiometric molar ratio of
      hydroxyapatite was obtained when the pH of the SBF was continuously adjusted to
      7.26 during precipitation. This precipitate has a fine-grained and laminated
      microstructure after sintering at 1000 degrees C in air. It seems that SBF can be
      used as a tool to study apatite-like precipitation in vitro when the pH of the
      solution is carefully controlled.

PMID- 9158858
TI  - Cross-linking of dermal sheep collagen with tannic acid.
AB  - The purpose of this study was to investigate cross-linking of (damaged) collagen
      by tannic acid, with a view to reconsider its use as a possible therapeutical
      agent in the treatment of burn wounds. Because of contradictory reports in the
      literature, and increased purity of tannic acid, this method has again become
      valuable for re-evaluation. A laboratory study using dermal sheep collagen was
      conducted to analyse the influence of several metal ions on collagen cross
      linking with tannic acid. The tannic acid concentration vs degree of cross
      linking, tannic acid uptake and release, influence of the addition of metal ions,
      and the rate of degradation of treated collagen were established. We have shown
      that tannic acid mediated collagen cross-linking in a concentration-dependent
      manner. Cross-linking was influenced by the presence of metal ions: Fe3+ and Ag+
      were shown to exert a stimulatory effect on the degree of cross-linking by a 2%
      tannic acid solution, whereas Zn2+ had an inhibitory effect Ce3+ Ca2+ and Na+ did
      not influence the degree of cross-linking. The degree of cross-linking was
      proportional to the uptake of tannic acid, which variod between 6 and 35 wt%.
      Reversibility of cross-linking was established. Tannic acid-treated dermal sheep
      collagen showed a slow degradation rate relative to differently cross-linked
      collagen materials when subjected to collagenase or pancreatic proteolytic
      enzymes. The results of this study suggest that tannic acid could have a function
      in vivo in burn treatment by binding burn toxins and inhibiting degradation of
      the (remaining) dermal matrix, and allows combination with metal ions as
      antimicrobials. Optimal cross-linking was obtained using a 2 wt% tannic acid
      solution; combination with Ce3+ as a potential antimicrobial agent is possible
      without diminishing cross-linking.

PMID- 9158859
TI  - Covalent linkage of recombinant hirudin to poly(ethylene terephthalate) (Dacron):
      creation of a novel antithrombin surface.
AB  - Thrombus formation and intimal hyperplasia on the surface of implantable
      biomaterials such as poly(ethylene terepthalate) (Dacron) vascular grafts are
      major concerns when utilizing these materials in the clinical setting. Thrombin,
      a pivotal enzyme in the blood coagulation cascade primarily responsible for
      thrombus formation and smooth muscle cell activation, has been the target of
      numerous strategies to prevent this phenomenon from occurring. The purpose of
      this study was to covalently immobilize the potent, specific antithrombin agent
      recombinant hirudin (rHir) to a modified Dacron surface and characterize the in
      vitro efficacy of thrombin inhibition by this novel biomaterial surface. Bovine
      serum albumin (BSA), which was selected as the "basecoat' protein, was reacted
      with various molar ratios of the cross-linker sulphosuccinimidyl 4-(N
      maleimidomethyl) cyclohexane-1-carboxylate (sulpho-SMCC; 1:5-1:50). These BSA
      SMCC complexes were then covalently linked to sodium hydroxide-hydrolysed Dacron
      (HD) segments via the cross-linker 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide
      hydrochloride (EDC). Covalent linkage of these complexes to HD (HD-BSA-SMCC) was
      not affected by any of the sulpho-SMCC cross-linker ratios assayed. rHir, which
      was initially reacted with 2-iminothiolane hydrochloride (Traut's reagent) in
      order to create sulphydryl groups, was then covalently bound to these HD-BSA-SMCC
      surfaces (HD-BSA-SMCC-S-rHir). The 1:50 (BSA: sulpho-SMCC) HD-BSA-SMCC-S-rHir
      segments bound 22-fold more rHir (111 ng per mg Dacron) compared to control
      segments and also possessed the greatest thrombin inhibition of the segments
      evaluated using a chromogenic substrate assay for thrombin. Further
      characterization of the HD-BSA-SMCC-S-rHir segments demonstrated that maximum
      thrombin inhibition was 20.43 NIHU, 14.6-fold greater inhibition than control
      segments (1.4 NIHU). Thrombin inhibition results were confirmed by 125I-thrombin
      binding experiments, which demonstrated that the 1:50 HD-BSA-SMCC-S-rHir segments
      had significantly greater specific thrombin adhesion compared to control
      segments. Non-specific 125I-thrombin binding to and release from the 1:50 HD-BSA
      SMCC-S-rHir segments was also significantly less than the control segments. Thus,
      these results demonstrate that rHir can be covalently bound to a clinically
      utilized biomaterial (Dacron) while still maintaining its ability to bind and
      inhibit thrombin.

PMID- 9158860
TI  - New drugs--reports of new drugs recently approved by the FDA. Lamivudine.

PMID- 9158861
TI  - Beyond enzyme kinetics: direct determination of mechanisms by stopped-flow mass
      spectrometry.
AB  - The development of soft ionization techniques has made mass spectrometry an
      efficient and essential tool for the determinations of the primary structures of
      peptides and proteins. Recently the technique has been extended at an explosive
      rate to noncovalent structures as well as dynamics of protein-protein
      interactions. We propose here that interfacing mass spectrometry with a stopped
      flow mixing device and applying these new techniques of soft ionization to
      enzymes undergoing catalysis will provide direct access to enzyme mechanisms,
      both kinetic mechanisms (which describe the comings and goings of substrates,
      products, and inhibitors) and chemical mechanisms (which describe the order of
      breaking and making chemical bonds). Transient-state measurements will provide
      the order of reaction events; steady-state measurements will provide the
      distribution and therefore the relative energy level of enzyme forms
      participating in those events; combining transient-state and steady-state
      measurements is therefore expected to provide sufficient information to construct
      a free energy diagram of the enzyme-catalyzed reaction.

PMID- 9158862
TI  - Helenanolide-type sesquiterpene lactones--III. Rates and stereochemistry in the
      reaction of helenalin and related helenanolides with sulfhydryl containing
      biomolecules.
AB  - The reactivity of the two potential Michael addition sites of the helenanolide
      type sesquiterpene lactone helenalin towards the physiological thiols glutathione
      (GSH) and cysteine (cys) in aqueous solution was investigated by 1H NMR
      spectroscopic experiments. In the presence of one molar equivalent of GSH, the
      reaction was shown to occur with high regio- and stereoselectivity at the beta
      position of C-2 in the cyclopentenone ring. Addition to the exocyclic methylene
      group at the lactone ring was found to occur in the presence, of GSH in molar
      ratios over 1:1, but proceeded at a rate 10 times smaller than at C-2 leading to
      the 2 beta,13(11 beta)-bis-glutathionyl adduct. In contrast, addition of free cys
      highly favoured the exocyclic methylene group. Addition of GSH to the
      cyclopentenone of 11 alpha, 13-dihydrohelenalin (plenolin) showed the same
      characteristics as observed with helenalin while 2 alpha-acetoxy-2,3-dihydro-4
      beta H-helenalin (chamissonolide) did not form an adduct when incubated with an
      equimolar amount of GSH. Explanations for the observed differences in reactivity
      of the two potential reaction sites based on MO computations are given and
      implications for the biological activity of this type of sesquiterpene lactones
      are discussed.

PMID- 9158863
TI  - Synthesis and analgesic effects of 3-substituted 4,6-diarylpyridazine derivatives
      of the arylpiperazine class.
AB  - A new series of 4,6-diaryl pyridazines substituted in the 3-position by
      arylpiperazinyl moieties was synthesized and evaluated for analgesic activity.
      Five out of the nine tested compounds possessed significant antinociceptive
      effects in the phenylbenzoquinone-induced writhing test (PBQ test) with ED50
      values ranging from 26.0 to 37.7 mg/kg ip. The most active derivatives 2a, 2d and
      2h had a low toxicity (LD50 > 800 mg/kg ip) but showed some sedative and
      neurotoxic effects from the dose of 50 mg/kg ip. The three selected pyridazines
      were devoid of activity in the hot-plate test. However, analgesic activity of 2d
      and 2h was significantly reversed by naloxone in the PBQ test. Administered at
      the low dose of 5 mg/kg ip, 2h greatly potentiated the antinociceptive response
      induced by morphine (0.15 mg/kg sc). In addition, analgesic effects of 2h (2.5
      mg/kg ip) were also potentiated by 5-hydroxytryptophan combined with carbidopa.
      These results suggest that pyridazine 2h induces analgesia, which is mediated via
      both opioid and serotonergic mechanisms.

PMID- 9158864
TI  - A search for pyrophosphate mimics for the development of substrates and
      inhibitors of glycosyltransferases.
AB  - The design and synthesis of several beta-1,4-galactosyltransferase inhibitors are
      reported. Mimics of the pyrophosphate-Mn2+ complex were the focus of the design.
      Malonic, tartaric, and monosaccharide moieties were used as replacements of the
      pyrophosphate moiety, and galactose or azasugars with potent galactosidase
      inhibitory activity were used as the 'donor' component. Compound 6, in which
      glucose was used as the pyrophosphate-Mn2+ complex mimic and galactose as the
      'donor' component, showed the best inhibitory activity towards the transferase
      with a Ki of 119.6 microM.

PMID- 9158865
TI  - 3N-methylbiphenylsulfonylurea and -carbamate substituted imidazo[4,5-b]pyridines.
      Potent antagonists of the ANG II AT1 receptors.
AB  - The synthesis and the SAR study of imidazo[4,5-b]pyridine biphenyl sulfonylureas
      and -carbamates as highly potent AT1-selective ANG II receptor antagonists are
      described. Several members of this new class of antagonists efficiently inhibited
      the ANG II-induced pressor response in pithed rats after iv and intraduodenal
      (id) administration.

PMID- 9158866
TI  - Cysteine proteases such as papain are not inhibited by substrate analogue
      peptidyl boronic acids.
AB  - Peptidyl boronic acids that are close structural analogues of good substrates
      have been prepared and evaluated as potential transition state analogue
      inhibitors of the representative cysteine protease, papain. However, no
      inhibition could be detected at concentrations up to 10 mM. The reasons for the
      lack of inhibition were sought from molecular modeling. Molecular mechanics and
      semi-empirical quantum mechanics calculations indicated that the absence of
      inhibition was due to boronic acid-cysteine protease tetrahedral complexes being
      0.79 kcal mol-1 less stable than their preceding noncovalent EI-complexes. In
      contrast, an analogous boronic acid-serine protease tetrahedral complex was
      calculated to be 2.74 kcal mol-1 more stable than its precursor Michaelis EI
      complex. It thus appears that boronic acids are ineffective inhibitors of
      cysteine proteases due to the thermodynamic favoring of a weak EI-complex
      preceding tetrahedral intermediate formation, and that any oxyanion hole
      stabilization of the subsequent tetrahedral intermediate cannot overcome this
      energy handicap.

PMID- 9158867
TI  - A microgonotropen branched decaaza decabutylamine and its DNA and
      DNA/transcription factor interactions.
AB  - The central pyrrole of a site-selective DNA minor groove binding tripyrrole
      peptide 1 has been attached to a branched decaaza decabutylamine via a -(CH-2)3
      NHCO-(CH2)-3 linker to provide the decaaza-microgonotropen (8). The decaaza
      decabutylamine moiety of 8 was designed to have a much greater affinity to the
      phosphodiester linkages of the backbone of DNA. Employing Hoechst 33258 (Ht) as a
      fluorescent titrant, the equilibrium constants for the binding for of 8 to the
      hexadecameric duplex d(GGCGCA3T3GGCGG)/d(CCGCCA3T3GCGCC) and to calf thymus DNA
      were determined. The log of the product of equilibrium constants (log Kl1Kl2) for
      1:1 and 1:2 complexes formation at A3T3 is 17 (35 degrees C). Results of studies
      of the inhibition of the binding of several proteins to target DNA are discussed.
      Binding of the E2F1 transcription factor to its DNA target is 50% inhibited at
      approximately 2 nM concentration of 8.

PMID- 9158868
TI  - Design, synthesis, and in vitro activities of benzamide-core glycoprotein
      IIb/IIIa antagonists: 2,3-diaminopropionic acid derivatives as surrogates of
      aspartic acid.
AB  - In an effort to discover novel nonpeptide glycoprotein IIb/IIIa (GPIIb/IIIa,
      alpha IIb/beta 3) inhibitors, we investigated RGD mimetics featuring a 3
      substituted benzoic acid as the core, benzamidine as the basic moiety, and a
      series of beta- and alpha-substituted beta-alanine derivatives as aspartic acid
      surrogates. It was found that the use of beta-methyl beta-alanine slightly
      improved the anti-aggregant potency in human platelet-rich plasma over the
      unsubstituted beta-alanine compound, while beta-substitution with a
      trifluoromethyl group resulted in considerable loss in activity. Significant
      enhancement (up to 100-fold) in potency was obtained when the beta-alanine was
      replaced with N2-substituted 1-2,3-diaminopropionic acid derivatives. Among the
      three types of alpha-substituents (carbamate, amide, and sulfonamide)
      investigated, no apparent preference was observed with respect to in vitro
      potency. However, alkyl groups were more favorable than arylalkyl groups (Cbz) in
      the carbamate analogues. We also investigated piperidine, piperazine, and N
      formamidinopiperidine as replacements for the benzamidine moiety. The former two
      replacements led to a drop in potency while the latter replacement resulted in
      maintenance of activity as compared with the corresponding benzamidine analogue.

PMID- 9158869
TI  - Synthesis of N-glyoxylyl peptides and their in vitro evaluation as HIV-1 protease
      inhibitors.
AB  - A series of novel synthetic peptides containing an N-terminal glyoxylyl function
      (CHOCO-) have been tested as inhibitors of HIV-1 protease. The N-glyoxylyl
      peptide CHOCO-Pro-Ile-Val-NH2, which fulfills the specificity requirements of the
      MA/CA protease cleavage site together with the criteria of transition state
      analogue of the catalyzed reaction, was found to be a moderate competitive
      inhibitor although favorable interactions were visualized between its hydrated
      form and the catalytic aspartates using molecular modeling. Increasing the length
      of the peptide sequence led to compounds acting only as substrates.

PMID- 9158870
TI  - Synthesis and biological evaluation of 1,1-dichloro-2,3-diarylcyclopropanes as
      antitubulin and anti-breast cancer agents.
AB  - Z-1,1-Dichloro-2,3-diphenylcyclopropane (1) is an effective anti-breast cancer
      agent in rodents and in cell culture. We recently determined that 1 inhibits
      tubulin assembly in vitro and causes microtubule loss in breast cancer cells,
      leading to accumulation in the G2/M portion of the cell cycle. Aryl ring
      halogenated, methoxylated and benzyloxylated derivatives of 1, as well as its E
      isomer and the dichlorocyclopropyl derivative of diethylstilbestrol (DES), were
      synthesized and tested for their ability to inhibit, the assembly of tubulin into
      microtubules. Including 1, 17 cyclopropyl compounds were tested. One (Z-1,1
      dichloro-2-(4-methoxyphenyl)-3-phenylcyclopropane (12)) was found to be more
      active than 1. In addition, E-1,1-dichlorocyclopropylDES (17) was more potent
      than DES. The E-isomer of 1 (16) was inactive. The cytostatic activities of the
      compounds against MCF-7 and MDA-MB231 human breast cancer cells, and their
      abilities to perturb microtubules in MCF-7 cells were also evaluated. Z-Dichloro
      2-(4-fluorophenyl)-3-phenylcyclopropane (5), Z-1,1-dichloro-2-(4-fluorophenyl)-3
      (4-methoxyphenyl)cyclopropane (11), and Z-1,1-dichloro-2-(4-methoxyphenyl)-3
      phenylcyclopropane (12) were more potent than 1 against the breast cancer cells.

PMID- 9158871
TI  - Thiol-independent DNA cleavage by a leinamycin degradation product.
AB  - To understand the mechanism of action of a novel antitumor antibiotic leinamycin
      (1) which induces single-strand scission of DNA in the presence of thiol, the
      reaction of 1 with thiol in aqueous conditions was investigated. Two major
      degradation products were obtained from 1 in the presence of thiol. 2 was an
      inactive product, while 3 caused DNA cleavage in the absence of thiol. The DNA
      cleaving activity of their synthetic derivatives indicates that the DNA
      alkylation and subsequent strand scission by leinamycin require the conversion of
      leinamycin to an electrophilic episulfonium species.

PMID- 9158872
TI  - Synthesis and structure-activity relationship studies in a series of 2
      substituted 1,3-dioxolanes modified at the cationic head.
AB  - To develop ligands that may be useful in exploring muscarinic receptor
      heterogeneity, we synthesized a series of analogues of 2,2-diphenyl-[1,3]
      dioxolan-4-ylmethyl-dimethylamine oxalate and methiodide bearing a modified
      cationic head. These compounds, when tested on tissues containing the three
      subtypes M1, M2, and M3, behaved as muscarinic antagonists whose results showed
      that different substituents on the quaternary and tertiary nitrogen affect
      affinity and selectivity in different ways. In particular comparison of the
      affinities of these ligands with those of the reference compounds points out that
      compounds bearing an ethyl substituent improve the affinity of the molecule at
      the three subtypes while compounds bearing a phenethyl substituent are more
      selective for the M3 sites.

PMID- 9158873
TI  - Inhibitors of acyl-CoA:cholesterol acyltransferase: novel trisubstituted ureas as
      hypocholesterolemic agents.
AB  - Our continued interest in developing novel, potent acyl-CoA:cholesterol
      acyltransferase (ACAT) inhibitors, and our discovery of several active series of
      disubstituted urea ACAT inhibitors, have led us to investigate a series of
      trisubstituted ureas that are structural hybrids of our disubstituted series and
      of a trisubstituted urea ACAT inhibitor series disclosed by scientists at
      Lederle. This investigation has led to the discovery of novel trisubstituted
      ureas, several of which inhibit ACAT in the nanomolar range and effectively lower
      total plasma cholesterol when administered as a diet admixture in an acute model
      of hypercholesterolemia in rats. One analogue (35) also lowered total cholesterol
      as efficaciously as CL 277,082 in our chronic hypercholesterolemic rat model. The
      most notable finding of this study is that the SAR of the trisubstituted ureas
      diverges from that seen in our previously disclosed disubstituted urea series.
      This series showed optimal activity with 2,4-difluoro and 2,4,6-trifluoro
      substitution on the urea N-phenyl, whereas the disubstituted series showed
      optimal activity with bulky 2,6-disubstitution on the phenyl ring.

PMID- 9158874
TI  - Synthesis of two optically active calcium channel antagonists labelled with
      carbon-11 for in vivo cardiac PET imaging.
AB  - (+/-)-S11568 (1, 3-ethyl-5-methyl-(+/-)-2-[(2-(2-aminoethoxy)ethoxy) methyl]-4
      (2,3-dichlorophenyl)-6-methyl-1,4-dihydropyridine-3, 5-dicarboxylate), has an in
      vitro profile of high potency and of high selectivity for the low-voltage
      dependent. L-type calcium channel. In in vitro binding studies, it displaced
      specifically bound (-)-[3H]PN 200-110 (isradipine (2), the reference molecule for
      in vitro studies) from cardiac and vascular smooth muscle preparations with
      potencies of 5.6 and 51 nM, respectively. It also appears as a pure
      pharmacological antagonist acting at a single channel L-type and free of any
      interaction at the benzothiazepine binding site such as amlodipine (3). Both
      enantiomers of S11568 have in vitro activities, the dextro isomer S12967 ((+)-1)
      being 6 to 18-fold less potent than the levo one S12968 ((-)-1). Two couples of
      optically active labelling precursors of S11568, ((-)-10/(+)-10 and (-)-14/(+)
      14) have been synthesized using a modified Hantzsch's dihydropyridine synthesis.
      In both cases, the enantiomers were separated by preparative chiral HPLC. They
      both have been independently labelled with carbon-11, using [11C]diazomethane or
      [11C]iodomethane to give multimilliCurie quantities of (-)-1 (S12968) and (+)-1
      (S12967) with high specific activities (500-1000 mCi/mumol, 18.5-37.0 GBq/mumol).
      Both enantiomers appear suitable for PET experiments: their myocardial
      concentration increases after a bolus injection to reach a maximum in 2 min and
      then remains on a plateau with a slight downslope while the blood concentration
      falls rapidly. Myocardial uptake was threefold higher than lung uptake, leading
      to a good contrast on PET images. The present preliminary biological results
      obtained in Beagle dogs showed that both enantiomers have similar myocardial
      kinetics and in vivo affinity for the left ventricular myocardium.

PMID- 9158875
TI  - Synthesis and biological evaluation of orally active matrix metalloproteinase
      inhibitors.
AB  - The synthesis and biological evaluation of orally active inhibitors of matrix
      metalloproteinase are reported. Modifications of the P2' position and the alpha
      substituent of hydroxamic acid derivatives were carried out, and revealed that
      the P2' substituent influenced the MMP inhibitory activities in vitro and in
      plasma after oral administration. The hydroxamates with phenylglycine at the P2'
      position were absorbed well orally. Compound 15e, which exhibited the longest
      duration of inhibitory activity in plasma after oral administration among the
      phenylglycine derivatives (5a-5d, 15a, 15c, 15e), was evaluated in a rat adjuvant
      arthritis model. A reduction in hind foot pad swelling and improvements of some
      inflammatory parameters were demonstrated when the compound was administered
      orally. These results indicate the potential of MMP inhibitors for rheumatoid
      arthritis.

PMID- 9158877
TI  - Pharmacokinetic evaluation of liposomal encapsulated ampicillin in male and
      female rats.
AB  - The dispositions of free and liposomal entrapped ampicillin were compared in male
      and female rats after i.v. administration. Serial blood samples were collected
      for 2 h in the free drug study and 12 h for the liposomal formulation.
      Pharmacokinetic parameters obtained with free drug were not significantly
      different between genders. However, gender significantly influenced the
      disposition of liposomal encapsulated ampicillin. While no difference was
      observed in distribution t1/2 between genders, female rats had a shorter MRT,
      smaller Vss and Vt, and faster clearance as compared to male rats. In a second
      study, spleen, liver, kidney, heart, and lung were harvested post-injection of
      free and liposomal entrapped ampicillin. Free ampicillin did not distribute
      extensively into the tissue compartment and no gender difference was noted. In
      contrast, liposomal encapsulation resulted in a substantial tissue uptake. In
      general, female rats had higher concentrations in the spleen and lung as compared
      to male rats. In vitro plasma stability was not significantly different,
      suggesting that destabilization of the liposomes does not play a large role in
      the dispositional differences observed in these studies. However, in vivo
      interaction of liposomes and plasma lipoproteins may influence the disposition of
      encapsulated drug.

PMID- 9158876
TI  - N-(5-substituted) thiophene-2-alkylsulfonamides as potent inhibitors of 5
      lipoxygenase.
AB  - Compound 4k N-[5-(4-fluoro)phenoxythien-2-yl]methanesulfonamide is representative
      of a new class of potent inhibitors of 5-lipoxygenase (5-LO). These versatile
      compounds exhibit dose-dependent inhibition of 5-LO with IC50s ranging from 20
      100 nM in the rat basophilic leukemia (RBL-1) cell homogenate assay and
      submicromolar IC50s in both the RBL-1 and human peripheral blood leukocyte (PBL)
      whole cell assays. Compound 4k also showed significant anti-inflammatory activity
      in the adjuvant arthritic rat at an oral dose of 3 mg/kg.

PMID- 9158878
TI  - Prediction of the therapeutic dose for benzodiazepine anxiolytics based on
      receptor occupancy theory.
AB  - Many benzodiazepines (BZPs) are now used as anxiolytics with nearly 200-fold
      variety of therapeutic doses. The variation of the doses of BZPs is due to
      differences both in their pharmacokinetics and in their receptor binding
      characteristics. The purpose of this study is to clarify the mechanism of the
      differences in therapeutic dose by retrospective analyses and to develop a system
      for the quantitative estimation of optimal doses of BZPs. The values of receptor
      dissociation constant (Kd), which indicates the binding affinity of each BZP at
      the receptor site, were obtained from a number of works based on in vitro binding
      experiments. The plasma unbound concentrations of the BZPs and their active
      metabolites were calculated using the reported values of their total plasma
      concentrations after average oral doses of the BZPs and the values of their
      plasma unbound fractions, which were also taken from the literature. There were
      log-linear relationships between the Kd values of BZPs and their average
      therapeutic doses or maximum plasma concentrations, but the correlation
      coefficients were relatively small (r < 0.77). In contrast, a good log-linearity
      (r = 0.96) was observed in the correlation between their Kd values and the
      effective plasma unbound concentrations considering the active metabolites. This
      finding indicates that the receptor occupancy after administration of therapeutic
      dose of BZPs is consistent (52.3 +/- 3.2%) among the BZPs. In this study, we also
      develop a possible system for estimating the appropriate doses of BZPs based on
      receptor occupancy theory.

PMID- 9158879
TI  - Pharmacokinetic stereoselectivity of troglitazone, an antidiabetic agent, in the
      KK mouse.
AB  - Troglitazone, an oral antidiabetic agent, is an equal mixture of four
      stereoisomers involving two asymmetric centres. In the present study, the
      stereoselectivity of in vitro epimerization in plasma and organ homogenate and in
      vivo plasma disposition in the KK mouse, an animal model of non-insulin-dependent
      diabetes, was examined. In the incubation experiments at 37 degrees C, there was
      a fivefold to eightfold acceleration of epimerization at the 5 position of the
      thiazolidine ring in KK mouse plasma compared with that in buffer. However, no
      inversion at the 2 position of the chroman ring was observed. In addition, there
      was an approximately 1.3-fold difference in the epimerization rates among
      stereoisomers at the 2 position of the chroman ring. However, there were no
      differences in the values of the equilibrium constants of epimerization, and the
      ratio of epimerization among stereoisomers at the 5 position of thiazolidine ring
      was almost unity. The acceleration of epimerization is thought to be due to the
      high degree of protein binding because of the relationship between the initial
      epimerization rate and the dilution ratio of the plasma. Although acceleration of
      epimerization was also observed in the 20% homogenates of liver, kidney, and
      intestine of the KK mouse, the degree of stereoselectivity was lower than in
      plasma. The analysis of the plasma disposition after intravenous administration
      of troglitazone stereoisomers, using a kinetic model, indicated that the
      metabolic clearance in the liver showed a 2.5-fold maximum difference among
      stereoisomers and that the stereoselectivity of epimerization was low.

PMID- 9158880
TI  - Pharmacokinetics of MDL 26479, a novel benzodiazepine inverse agonist, in normal
      volunteers.
AB  - MDL 26479 is a new drug undergoing clinical evaluation for the treatment of
      depression and for memory loss associated with Alzheimer's disease. As part of a
      dose tolerance trial, the single- (SD) and multiple-dose (MD) pharmacokinetics of
      MDL 26479 were evaluated in healthy male volunteers. SDs ranging from 2 to 465
      mg, and doses of 30, 60, and 120 mg administered twice daily for 28 d, were
      examined. Serial blood samples were collected for up to 48 h. Plasma MDL 26479
      concentrations were determined by HPLC. Plasma MDL 26479 concentration versus
      time profiles increased rapidly, followed by multiexponential decline. Time to
      maximum plasma concentration increased over the 230-fold SD range from 0.5 to 3.8
      h. Maximum concentrations and areas under the concentration versus time curves
      increased disproportionately with dose. Apparent oral clearance estimates
      decreased from 52.9 to 13.8 Lh-1. MD pharmacokinetic parameters for doses from 30
      to 120 mg were consistent with those observed following SD, thus indicating that
      SD pharmacokinetics are predictive of MD. SD and MD terminal half-life estimates
      were similar and independent of dose.

PMID- 9158881
TI  - Distribution of antihistamines into the CSF following intranasal delivery.
AB  - The preferential absorption of certain drug compounds from the nasal cavity into
      the cerebrospinal fluid (CSF) raises questions regarding the transport processes
      controlling drug disposition following intranasal delivery. The disposition
      characteristics of several structurally similar antihistamine compounds,
      hydroxyzine, chlorpheniramine, triprolidine, and chlorcyclizine, into the CSF
      following nasal administration were studied using the rat as an animal model. The
      antihistamines were administered either intranasally or intra-arterially, and
      serial CSF and plasma samples were collected from the cisterna magna and the
      femoral artery, respectively. The drug levels in CSF and plasma were assayed by
      HPLC. Hydroxyzine concentrations in plasma and CSF were found to be significantly
      greater than most of the other compounds tested. In addition, hydroxyzine also
      showed the most rapid systemic absorption following nasal administration.
      Interestingly, the hydroxyzine levels in CSF following intranasal administration
      were significantly higher than those following intra-arterial administration. The
      AUC ratios between CSF and plasma for hydroxyzine after intranasal and intra
      arterial administration were 4.0 and 0.4, respectively. The AUC ratios for
      triprolidine, the other antihistamine with measurable CSF concentrations, were
      0.5 and 0.7, respectively. The distribution of antihistamines from the nasal
      membrane into the CSF appears to be controlled by a combination of their
      molecular properties. It also appears that the intranasal delivery of drugs with
      optimal physicochemical characteristics can result in an improved CNS
      bioavailability compared to those achieved from an equivalent parenteral dose.

PMID- 9158882
TI  - Pharmacokinetics of elemental platinum (ultrafiltrate and total) after a thirty
      minute intravenous infusion of ormaplatin.
AB  - Preclinical data suggest that ormaplatin (tetrachloro-(dl-trans)-1, 2
      diamminocyclohexaneplatinum) has substantial activity in cisplatin-resistant
      tumor models and may be less nephrotoxic than cisplatin. Based on these data we
      initiated a phase I clinical trial in patients with refractory metastatic cancer.
      This report characterizes the pharmacokinetic profile of both the total plasma
      concentrations of elemental platinum and the unbound ultrafiltrate concentrations
      of elemental platinum, following a 30 min intravenous infusion of ormaplatin.
      Platinum concentrations were determined by AAS, and pharmacokinetic parameters
      for both the total plasma concentration and the ultrafiltrate concentration of
      elemental platinum were determined using both compartmental and noncompartmental
      methods. Twenty-eight patients (14 males and 14 females; median age, 58) received
      ormaplatin. There was a linear relationship between Cmax and dose (r2 = 0.945)
      and AUC and dose (r2 = 0.976). Ormaplatin is more accurately described by a two
      compartment model than by a one-compartment model. The distribution half-life
      (t1/2 alpha) was 0.3 h and the terminal half-life (t1/2 beta) was 39.1 h. The
      volume of the central compartment (V) was 68.6 L and the volume of distribution
      at steady state (Vdss) was 183 L. Like total plasma platinum, unbound platinum is
      also best characterized by a two-compartment model. The elimination of free
      platinum is also biphasic with a distribution half-life (t1/2 alpha) of 0.3 h and
      a terminal half-life (t1/2 beta) of 19.3 h. The mean volume of the central
      compartment (V) was 200.5 L, and the mean volume of distribution at steady state
      (Vdss) was 560.5 L. Clinical development of ormaplatin has been terminated due to
      increased frequency of neurological complications noted over other platinum
      agents; however, the pharmacokinetics are, in general, similar to those of other
      clinically used platinum compounds.

PMID- 9158883
TI  - Pharmacokinetics and safety of single intravenous and oral doses of dolasetron
      mesylate in healthy women.
AB  - Twenty-four healthy women received 2.4 mg kg-1 dolasetron mesylate (1.8 mg kg-1
      dolasetron base) by a 10 min intravenous administration and by oral
      administration. Pharmacokinetics of dolasetron and of its active reduced
      metabolite MDL 74156 were monitored for 48 h in plasma. Urine was collected from
      0 to 48 h, blood pressure and heart rate were measured at 0, 0.08, 1, 2, 12, 24,
      and 36 h, and ECGs were measured at 0, 0.08 (intravenous only), 1, 2, and 36 h
      after dosing. Dolasetron was widely distributed and rapidly reduced (mean t1/2 =
      0.23 h) to MDL 74156 (mean t1/2 = 8.05 and 9.12 h after intravenous and oral
      administration respectively). MDL 74156 was extensively distributed; between 27
      (oral route) and 33% (intravenous route) was eliminated unchanged in urine.
      Safety assessment showed mild to moderate headache, dizziness, and hot flushes
      after the intravenous administration and headache, abdominal cramps or pain, and
      constipation after oral administration. Small and clinically non-significant
      changes in PR, QRS, and QTc intervals were observed. We conclude that there is no
      obvious difference in dolasetron pharmacokinetics between healthy women and men
      and that dolasetron can be used as safely in women as in men.

PMID- 9158884
TI  - Effects of plastic anti-pecking devices on food intake and behaviour of laying
      hens fed on pellets or mash.
AB  - 1. This study investigated effects of plastic anti-pecking devices on food intake
      and behaviour to assess their applicability in commercial layer flocks. 2. In
      experiment 1, 72 individually caged ISA Brown pullets were fitted at 16 weeks of
      age (point of lay) with either 'ring' or 'bumper' beak devices or no device
      (control), half being fed on pellets and half on mash. The devices were held in
      place by lugs inserted in the nares. 3. There was evidence of discomfort
      immediately after fitting the devices, but not thereafter. In the first week, the
      devices reduced food intake, and were removed from 7 (15%) birds that lost weight
      consistently. Between 16 and 21 weeks, however, there were no significant effects
      of beak treatment or food form on either total food intake or egg production with
      the 65 remaining birds. 4. Beak treatment did not affect feeding efficiency (food
      intake per minute of feeding). The only behaviour affected was pecking at birds
      in adjacent cages, which was reduced with the ring device. 5. At 21 weeks, the
      birds were placed together in groups of 4 to 6 in 12 pens, each group consisting
      of birds from one of the 6 original treatments, and their behaviour was observed
      in experiment 2 between 21 and 23 weeks. 6. The only effects of beak treatment on
      behaviour were that pecking at pen walls was increased with the ring device,
      while pulling and eating feathers from group mates was seen mainly with control
      birds fed on pellets. Two birds were cannibalised in a control group on pellets.
      7. Devices came off 3 (7%) birds in experiment 1 and were replaced, and rings
      slipped over lower mandibles of 2 (5%) birds in experiment 2 and were corrected.
      8. At 23 weeks, beak lengths were increased with ring and bumper treatments, and
      pecking damage scores were low with all treatments. 9. It is concluded that these
      devices are not applicable commercially, but further trials would be justified
      with new improved designs.

PMID- 9158885
TI  - Bone characteristics and body weight of broilers in different husbandry systems.
AB  - 1. An experiment was conducted to determine the effect of husbandry systems on
      bone characteristics and body weight. Broilers were reared in 5 different
      husbandry systems: wire mesh (WM) floored cages from 0 to 7 weeks; WM floored
      cages from 0 to 3 weeks and then transferred to floor pens; plastic mesh (PM)
      floored cages from 0 to 7 weeks; PM floored cages from 0 to 3 weeks and then
      transferred to floor pens; floor pens from 0 to 7 weeks. 2. Body weight at 3
      weeks of age was affected by the husbandry systems, being greatest for the birds
      reared in floor pens. At 7 weeks of age, male broilers reared in PM floored cages
      had the lowest body weight and body weight gain from 4 to 7 weeks. 3. Humerus
      weight and ash content were affected by cage rearing whereas tibia weight and ash
      were not. Birds reared in PM cages had shorter tibia and humeri than birds reared
      in floor pens.

PMID- 9158886
TI  - Equating the perceived intensity of coloured lights to hens.
AB  - 1. Previous investigations of the effects of light colour on the productivity or
      behaviour of chickens have not equated the intensity of the different coloured
      lights. 2. Ten pullets (Warren Studler 128) were used to determine the perceived
      intensity of two colours at opposite ends of the visible spectrum (blue, peak
      wavelength 415 nm and red, peak wavelength 635 nm). 3. Initially half of the
      birds were trained with food rewards to detect the brighter of two white lights
      and half the dimmer one. 4. Two discrimination tests then investigated the
      generalisation of this learnt ability (to distinguish white lights of different
      intensity) to coloured lights. They were rewarded for distinguishing the
      brightness of red and blue filtered lights when blue intensity was initially high
      and gradually reduced, and when red intensity was initially low and gradually
      increased. The birds identified the lights as being of equal intensity when the
      blue light was 3.6 times as bright as the red. 5. A second test examined the
      situation in reverse. A bright red light that was reduced was compared to a dim
      blue light that was increased in intensity. The birds were again successful and
      identified the lights as of equal intensity when the blue was 3.1 times as bright
      as the red. A final test confirmed that there was no difference in the perceived
      intensity of blue and red lights in the ratios 3.6 or 3.1 : 1. 6. The difference
      in perceived red and blue light intensities was less than predicted from the
      spectral sensitivity curve for chickens. It was expected that the blue light
      would be perceived as dimmer than the red because the red filter transmitted more
      light than the blue and the tungsten filament light illuminating the filter
      emitted more long than short wavelength light. The observed discrepancy
      emphasises that perceived intensity is difficult to predict from spectroscopic
      measurements. 7. The birds then underwent a simple visual test, to discriminate
      the length of two lines, equally well in red or blue filtered lights that were
      equiluminescent as determined previously. 8. It is concluded that coloured lights
      can be equated for intensity by psychophysical testing, and that there was no
      difference in visual acuity under equiluminescent blue and red filtered lights.

PMID- 9158887
TI  - Effect of size and timing of photoperiod increase on age at first egg and
      subsequent performance of two breeds of laying hen.
AB  - 1. ISA Brown and Shaver 288 pullets were changed from 8 h to 8, 10, 13 or 16 h
      photoperiods at 42, 63, 84, 105, 126 or 142 d of age. 2. Age at first egg (AFE)
      was curvilinearly affected by the size and timing of the change in photoperiod.
      AFE was advanced most by a photoperiod change from 8 to 13 h made at 63 or 84 d.
      ISA birds were generally more responsive than Shaver to the photoperiod changes.
      3. Longer photoperiods significantly increased survivors' egg production, but
      decreased liveability to 504 d. so that eggs per hen housed were unaffected.
      Retarding AFE by 10 d reduced survivors' egg numbers by 7.0, but increased mean
      egg weight by 1.26 g. Egg output by Shaver birds was unaffected by AFE, but that
      of ISA was curvilinearly affected, with an apogee at an AFE of 135 d. In both
      breeds, egg weight and egg output were greater following an early or late, rather
      than a mid-term photostimulation. 4. Photoperiod significantly increased mean
      daily food intake during lay by 1.26 g/h. A 10 d retardation in AFE resulted in a
      reduction in food intake of 1 g/d. Efficiency of food conversion deteriorated
      according to the square of the photoperiod, and changed curvilinearly according
      to age at photostimulation. Food conversion efficiency improved by 0.05 g/g for
      each 10 d delay in AFE. 5. Shell quality was unaffected by AFE, but deteriorated
      with increasing photoperiod and was curvilinearly affected by age at
      photostimulation with the smallest shell weights associated with photostimulation
      at 63 d. The incidence of double-yolked (DY) egg production increased with
      photoperiod and decreased with delayed photostimulation. There was an exponential
      regression of DY eggs on AFE. 6. Body weight at first egg increased by 75 g/d
      delay in AFE, but body weight at 504 d of age was unaffected by AFE, photoperiod
      or age at photostimulation. Body weight gain during lay increased by 15 g/h
      increase in photoperiod, decreased by 6 g per 10 d delay in photostimulation and
      by 40 g per 10 d delay in AFE. Fat content at 504 d increased by about 10 g/kg
      and by 23 g/bird for each 10 d delay in AFE. 7. Mortality in lay increased by
      0.8%/h increase in photoperiod, but was unaffected by either age at
      photostimulation or AFE.

PMID- 9158888
TI  - Feeding and pecking behaviour in ostrich (Struthio camelus) chicks in captivity.
AB  - 1. Three sets of experiments were performed on two batches of ostrich chicks to
      investigate the factors affecting the pecking and feeding behaviour of grouped
      individuals. 2. Chicks showed no significant alteration of their feeding
      behaviour in response to raising pen walls in the rearing facility from 30 to 60
      cm. 3. Further analysis on a different set of birds revealed consistent short
      term individual differences in the frequency of feeding and non-feeding pecks. 4.
      There were significant pen effects on behaviour suggesting the possible
      development of a pen 'culture' of pecking behaviour. 5. Pecking behaviours in 26
      to 33 d-old chicks, with the exception of drinking, were generally negatively
      correlated, so any non-food pecking by a chick was generally associated with
      fewer pecks targeted at food. 6. By the age of two months chicks were pecking at
      food on the floor to a far greater extent than at any food presented in food
      trays.

PMID- 9158889
TI  - Genetic studies on primary antibody response to sheep erythrocytes in guinea
      fowl.
AB  - 1. The primary antibody response to sheep erythrocytes was determined by
      haemagglutination test in guinea fowl. The effects of various genetic and non
      genetic factors on immune response to sheep RBCs in guinea fowl were also
      estimated. 2. The immune response to sheep RBCs was normally distributed in
      guinea fowl with mean titre at 1.534 +/- 0.014. 3. In guinea fowl, effects on
      titre values of sire and variety (feather colour) were significant whereas sex
      and sex x variety interaction effects were non-significant. 4. The estimate of
      heritability for immune response to sheep RBCs in guinea fowl was 0.35 +/- 0.17.

PMID- 9158890
TI  - Heterophil/lymphocyte ratio as a selection criterion for heat resistance in
      domestic fowls.
AB  - 1. Two experiments were conducted to examine the Heterophil/Lymphocyte ratio
      (H/L) as criterion for selection for resistance to heat stress and some aspects
      of general resistance in domestic fowls. 2. The first experiment on a small
      sample (n = 64) of light breed Iraqi local fowls showed that this ratio could be
      used as an indicator of heat stress resistance. 3. The second experiment on a
      large sample (n = 1160) of heavy parent stock confirmed the results. It showed
      that there was a different H/L ratio for the two strains and that there was much
      individual variability in the H/L ratio within-strain that could be utilised for
      individual selection for heat resistance. 4. The H/L ratio was highly heritable;
      Resistant and Sensitive groups, defining all individuals with an H/L ratio over
      the upper 95% confidence limit as 'Sensitive' and those below as 'Resistant'
      produced progeny with significantly different H/L ratios. 5. There were
      indications of differences in mortality between the progeny of the Resistant and
      the Sensitive groups. 6. The H/L indicator could be used as a criterion to select
      for heat stress resistance.

PMID- 9158891
TI  - Pharmacokinetic evaluation of enrofloxacin in chickens.
AB  - 1. The pharmacokinetics and bioavailability of enrofloxacin in chickens were
      investigated following intravenous, intramuscular, subcutaneous and oral
      administration of 10 mg/kg body weight. A rapid distribution phase was followed
      by a slower elimination phase. 2. The apparent volume of distribution was 2.2
      l/kg. Absorption half lives were 0.37, 0.36 and 0.92 h; elimination half lives
      were 4.06, 4.48 and 4.29 h and bioavailabilities were 87.5%, 80.8% and 59.6%
      after intramuscular, subcutaneous and oral administration, respectively. The drug
      completely disappeared from all tissues after 3 days following oral
      administration. 3. Based on the bioavailability and disposition kinetics of
      enrofloxacin, administration of one dose per day should both be practical and
      adequate to maintain plasma enrofloxacin concentrations within the
      pharmacologically active but lower than tolerance limit.

PMID- 9158892
TI  - Carcase and meat quality in broilers either killed with a gas mixture or stunned
      with an electric current under commercial processing conditions.
AB  - 1. Carcase and meat quality were evaluated under commercial conditions in 400
      broilers either killed with a mixture of 30% carbon dioxide and 60% argon in air
      or stunned with a 50 Hz AC with clipped sine wave. 2. Compared with electrical
      stunning, killing broilers with the gas mixture eliminated or substantially
      reduced the prevalence of carcase and meat quality defects. 3. The results also
      showed that killing broilers with a mixture of 30% carbon dioxide and 60% argon
      would enable filleting (deboning) to be performed at 4 h post mortem without
      adversely affecting the cook loss or texture of breast meat.

PMID- 9158893
TI  - Microstructure of white and dark turkey meat batters as affected by pH.
AB  - 1. The effect of increasing the pH (4.5 to 7.5) of white and dark comminuted
      turkey meat on the microstructure of cooked batters was studied. 2. Both scanning
      and transmission electron micrographs revealed that low pH caused the formation
      of a dense aggregated gel matrix while increasing the pH resulted in more open
      structures. 3. At pH 7.5 both the white and dark meat exhibited superior water
      holding capacity (both raw and cooked) compared to the low pH treatments; all
      adjusted to 14% protein. 4. The high pH also resulted in a higher gel strength,
      while the low pH (4.5) produced a soft and crumbly texture. As pH was raised, gel
      strength gradually increased reaching a maximum at pH 7.5. Decreasing the pH
      resulted in lighter meat batters in both the white and dark turkey meat. 5.
      Muscle fibre microstructure appeared to be better preserved at the low pH
      treatments.

PMID- 9158894
TI  - Influence of activity and dietary energy on broiler performance, carcase yield
      and sensory quality.
AB  - 1. A total of 2560 male and female Ross broilers were raised to 42 days of age in
      a 2 X 2 treatment factorial arrangement experiment to investigate the influence
      of different degrees of physical activity and dietary energy on broiler
      performance, abdominal fat content, carcase yield and sensory quality. 2.
      Vertical fans were used to force the treatment birds to walk 3 to 4 times as far
      as the normal activity birds: birds were fed a normal and a high energy diet
      (12.55 compared with 13.81 MJ ME/kg) with the same energy/protein, energy/lysine
      and energy/methionine + cystine ratios. 3. High activity birds had greater body
      weight (+4.1%), food intake (+5.1%) and ME intake (+5.1%) than normal activity
      birds. Birds receiving high energy diet had a lower food conversion and food
      intake than birds receiving normal energy diet. There were no significant
      differences in body weight or ME intake between birds with different diets. 4.
      Slaughter yields, both absolute and relative to live body weight, were affected
      by activity or dietary energy to varying degrees. Breast meat was increased with
      more activity. The absolute weight of abdominal fat was independent of activity
      and in males the relative weight of abdominal fat was decreased in high activity
      birds. 5. Different degrees of activity and dietary energy had only minor
      influences on broilers sensory quality.

PMID- 9158895
TI  - Effect of the method of killing, interval between killing and neck cutting and
      blood vessels cut on blood loss in broilers.
AB  - 1. Broiler chickens were killed using 90% argon in air, or 30% carbon dioxide and
      60% argon in air or 120 mA per bird in a waterbath with a 50 Hz alternating
      electric current. Ventral or unilateral neck cutting was performed at 1, 3 or 5
      min after killing. In addition, a group of broilers was stunned with 120 mA per
      bird in a waterbath using 1500 Hz alternating current and were bled out-with a
      ventral neck cut within 20 s from stunning. 2. Blood leaving the neck wound was
      collected in a bin placed on an electronic balance and a computer program
      calculated the cumulative blood loss up to 100 s after neck cutting. 3. Bleed-out
      was significantly affected by killing method and time of neck cutting. Broilers
      killed with the carbon dioxide-argon mixture bled-out less than those killed with
      argon or 50 Hz electric current. When compared with the 1 min neck cutting
      interval, a delay of 3-or 5 min resulted in a lower bleed-out. High frequency
      electrical stunning and ventral neck cutting within 20 s resulted in a slightly
      higher bleed-out than those recorded for the killing methods. However, within
      argon killing, a delay of 3 or 5 min in ventral or unilateral neck cutting had no
      significant effect on the bleed-out. In broilers killed with the carbon dioxide
      argon mixture a 3 min delay in ventral neck cutting or a 5 min delay in
      unilateral neck cutting resulted in lower bleed-out. 4. Neck cutting of broilers
      within 5 min after argon killing or 3 min after killing with the carbon dioxide
      argon mixture would result in a satisfactory bleed-out.

PMID- 9158897
TI  - Effects of dietary crude protein content and food intake on the production of
      semen in two lines of broiler breeder males.
AB  - 1. The effects of dietary crude protein (CP) concentration and feeding rate on
      semen production and quality from 21 to 66 weeks of age were assessed in a
      factorial experiment with 48 caged broiler breeder males from 2 strains. 2. The
      probability of obtaining semen and semen volume were lower in one of the two
      strains but the concentration and yield of spermatozoa were similar. 3. There was
      no evidence that males which were fed on an increasing quantity of food produced
      more semen or a greater concentration of spermatozoa than males on a fixed
      allocation of 120 g/d food. 4. The concentration of spermatozoa was lower in
      males fed on a diet containing 160 compared with 120 g CP/kg. On termination of
      the experiment, average testes size was small and testicular function was absent
      in a large proportion of the males on the high protein diet.

PMID- 9158898
TI  - Effect of sweet, bitter and soaked micronised bitter lupins on broiler
      performance.
AB  - 1. The feeding value for broilers of sweet white lupins (Lupinus albus variety
      Hanti), bitter lupins (Lupinus angustifolius) and soaked micronised bitter lupins
      was examined. 2. Four isocaloric and isonitrogenous diets were formulated; one
      contained no lupins and the other 3 contained 400 g/kg sweet, bitter or soaked
      micronised bitter lupins. The 3 lupin diets were blended appropriately to produce
      16 experimental diets containing 0, 50, 100, 200, 300 and 400 g/kg sweet, bitter
      and soaked micronised bitter lupins, respectively, and these were fed to Ross
      broilers for 6 weeks. 3. The feeding of diets containing bitter lupins to
      broilers at 300 and 400 g/kg and soaked micronised bitter lupins at 400 g/kg
      resulted in significantly different body weights, food intakes, food conversion
      ratios, carcase moisture and carcase fat contents from those of birds fed on the
      control diet. No significant differences were observed with carcase protein or
      carcase ash contents. 4. There were significant linear adverse responses with
      bitter and soaked micronised bitter lupins in most of the parameters studied
      whereas no responses were observed with sweet lupins as the dietary inclusion
      rate of the lupins increased. The soaked micronised bitter lupins performed
      better than the bitter lupins showing that the amount of bitter lupins in broiler
      diets can be increased by this method.

PMID- 9158896
TI  - Spread of an enteric 'marker' organism during evisceration of New York dressed
      poultry in a simulated kitchen environment.
AB  - 1. Five volunteers, with experience of eviscerating poultry or game birds in the
      home, each eviscerated three New York dressed chicken carcases that had been
      artificially inoculated in the colon with a readily identifiable "marker' strain
      of Escherichia coli. 2. In all cases, evisceration resulted in breakage of the
      intestines at one or more sites, often with leakage of gut contents, or extrusion
      of faeces from the cloaca because of pressure on the colon during the
      manipulations involved. 3. The marker organism was detected in the vent region
      and abdominal cavity of each carcase and sometimes on the breast and back, which
      appeared to reflect the degree of handling during evisceration, because the hands
      of each individual became heavily contaminated. 4. With some individuals, the
      marker also spread beyond the immediate preparation area and was detected on
      exposure plates. 5. Results support the view that evisceration of poultry in a
      domestic environment could lead to cross-contamination of other foods with any
      food-borne human pathogens present.

PMID- 9158899
TI  - Photorefractory period of the Muscovy duck (Cairina moschata): endocrine and
      neuroendocrine responses to day length after a full reproductive cycle.
AB  - 1. The Muscovy duck of equatorial origin, is photosensitive and its sexual
      maturation can be advanced by long days. The aim of this study was to investigate
      the photorefractory nature of the seasonal sexual rest in this species. 2. Sixty
      males were allocated to three groups of 20 birds each after completion of one
      full reproductive cycle in long days (16L:8D). Group A was transferred to longer
      days (20L:4D). Group B remained in 16L:8D. Group C was transferred to short days
      (6L:18D) for 9 weeks and then returned to 16L:8D. 3. Group B spontaneously
      redeveloped their testes and recrudescence, indicated by increased plasma
      concentrations of luteinising hormone and testosterone, started between the 4th
      and 10th week after total regression. Longer days (in group A accelerated
      recrudescence. Shorter days (in group C) delayed it, but the return to long days
      restored reproductive function. 4. In group C, the transfer to short days
      increased the hypothalamic content of luteinising hormone-releasing hormone. LHRH
      and secretion of the neuropeptide in vitro. The pituitary sensitivity to LHRH was
      increased in that group after the return to long days. 5. These effects show that
      the birds were photosensitive when daylength was changed 8 weeks after the
      completion of regression, and that short days were not necessary for the birds to
      regain photosensitivity. 6. The shortness of the regressed period and the
      spontaneous recrudescence in long days are more typical of equatorial birds than
      temperate zone species, which are more dependent on photoperiodic changes. The
      Muscovy duck probably retains features of its wild ancestor, which, living in
      equatorial latitudes, was more subject to non-photic synchronisers.

PMID- 9158900
TI  - Comparative study of ovomucoid isolated from Muscovy duck (Cairina moschata),
      domestic goose (Anser anser) and domestic duck (Anas platyrhynchos).
AB  - 1. Ovomucoids were purified from Muscovy duck, domestic duck and domestic goose.
      2. Peptide maps of cyanogen bromide-cleaved ovomucoids from Muscovy duck and
      domestic duck were very similar to one another, but differed from that of goose.
      3. Muscovy duck ovomucoid showed the same protease inhibitory pattern as
      ovomucoid from domestic duck, inhibiting trypsin in the molar ratio of 1:2 and
      chymotrypsin 1:1. 4. Inhibitory complexes could be detected between chymotrypsin
      and ovomucoid from both Muscovy and domestic duck, but not from goose, by using
      non-denaturing gels. 5. No complexes could be detected between DFP-inactivated
      chymotrypsin and any of the ovomucoids. 6. The results show that of ovomucoid
      from Muscovy duck more closely resembles that from domestic duck than goose.

PMID- 9158901
TI  - Effect of feeding clinoptilolite (zeolite) on the performance of three strains of
      laying hens.
AB  - 1. One hundred and twenty 16-week-old single combed pullets of three strains were
      fed on a diet containing 135 g protein/kg with or without 50 g clinoptilolite/kg
      in a trial with 20 hens per treatment. Sterile river sand replaced clinoptilotile
      in the control diet in order to keep the diets isoenergetic. The hens were
      individually caged in a naturally ventilated laying house and fed one of the two
      diets for ten 28-d periods. 2. Significant dietary effects of feeding
      clinoptilolite were observed with number of eggs laid per hen, shell thickness,
      efficiency of food utilisation and droppings moisture content. No significant
      dietary effects between treatments were observed with body weight, age at first
      egg, egg weight. Haugh units, food intake/hen and rate of amino acid absorption
      of radioactive lysine and methionine into the bloodstream. Significant
      differences between strains were observed with regard to all parameters except
      food intake/hen. There were no significant strain X clinoptilolite interactions.

PMID- 9158902
TI  - Chemical composition of the pearl grey guinea fowl.
AB  - 1. The growth of the chemical components of the body of the Pearl Grey guinea
      fowl from hatching till 127 days of age was evaluated in this study. 2. The
      Gompertz equation is suitable to describe the growth of the different chemical
      components over time. 3. Body and feather fat, respectively, were estimated by
      subtracting the predicted weights of all other components from those of body and
      feather weights. This leads to an overestimation of body fat content, and
      erroneous estimated values for feather fat.

PMID- 9158904
TI  - Crossing the line from physical discipline to child abuse: how much is too much?
AB  - OBJECTIVE: The aim of this paper was to better differentiate physical discipline,
      corporal punishment, and physical child abuse based on samples drawn from the
      United States. METHODOLOGY: The American literature was examined to differentiate
      these three constructs, first on such dimensions as severity, intention, and
      child effects; and second on key contextual or environmental factors empirically
      associated with higher rates of violent behavior in families. Third, normative
      data on parental spanking frequencies were summarized to better operationalize
      patterns of physical discipline among abusive and nonabusive parents. RESULTS:
      Five articles that met selection criteria revealed that abusive parents spanked
      their children more often than did nonabusive parents. Aggregated data from
      nonabusive parents were used to compute a continuum or "normal range" of daily
      spanking frequencies from 0 to 5.73 (M = 2.5) times in 24 hours. CONCLUSION:
      While further research is needed to address spanking intensity, severity, and
      context, results of the research suggest that "relative exposure" to spanking may
      be an additional risk marker for abuse when considered with other known
      indicators or risk factors.

PMID- 9158903
TI  - Parental accounts regarding the physical punishment of children: discourses of
      dis/empowerment.
AB  - OBJECTIVE: In the light of the psychological literature (e.g., Bettleheim, 1987)
      which indicates various contradictions surrounding the talk about and practice of
      the physical punishment of children (PPC), the main aim of the present study is
      to identify and examine the rationale(s) used by parents which bolster(s) PPC.
      METHODOLOGY: Data collection--semistructured interviews carried out with 10
      parents (nine female, one male). Data analysis--discourse analysis (e.g., Potter
      & Wetherall, 1987), a form of qualitative data analysis which is sensitive to the
      range and complexity of accounts (or discourses) presented by participants.
      Hence, we explore the various (often conflicting) discourses deployed by parents
      while talking about PPC, an approach which has not been used before in the study
      of parental discipline. RESULTS: Various oppositional discourses were used by the
      parents, each of which implies diverse justifications and consequences. Four in
      particular were identified--PPC as (1) pedagogic (educational). (2) cathartic
      (need relief); (3) individualistic (power assertion); (4) cyclical (reproduction)
      -and five instances of contradiction explicated with reference to the particular
      discursive context. CONCLUSION: Much confusion and complexity regarding PPC is
      evident from parental talk which is marked by discursive variation and
      contradiction. These discursive collisions notwithstanding, the participant's
      discourse generally implies the oppressive positioning of children and,
      consequently, offers support for physical punishment. The study also highlights
      the utility of discourse analysis as a method for interrogating PPC--and indeed
      other phenomena related to child abuse and neglect.

PMID- 9158905
TI  - Attitudes of the Singapore public to actions suggesting child abuse.
AB  - OBJECTIVE: The aim was to ascertain the views of the Singapore public on the
      acceptability of actions of an abusive nature. METHOD: In-depth interviews were
      carried out with 401 randomly sampled respondents in relation to a range of
      actions. Questions were asked concerning the acceptability of 18 actions, whether
      circumstances might justify eight of them, how respondents felt about reporting
      child abuse and whether they could recall any case they had come across. RESULTS:
      Respondents strongly disapproved of sexually motivated acts, and were more
      disapproving of physical abuse or neglect than of emotional abuse or neglect.
      Circumstances did affect how the less extreme actions were viewed. Respondents
      supported reporting child abuse, but were somewhat against mandatory reporting.
      They were able to recall details of a number of possible cases. CONCLUSION: We
      argue that definitions of child abuse should be general and not tied to specific
      actions, since the effects of actions may vary across cultures, and should be
      treated as an empirical matter. This allows a research agenda that focuses on the
      consequences of actions rather than issues of definition.

PMID- 9158906
TI  - Infant abuse runs in families of group-living pigtail macaques.
AB  - OBJECTIVE: The aims of this study were to investigate genealogical and
      demographic influences on maternal abuse and neglect of offspring in pigtail
      macaques and identify some maternal and infant characteristics that may be risk
      factors for abuse or neglect. METHOD: Infant abuse and neglect were investigated
      in five large families of group-living pigtail macaques over a period of 33-years
      (5-7 generations). The data were obtained from the Animal Records of the Yerkes
      Regional Primate Research Center. RESULTS: Abuse and neglect are likely to be two
      distinct phenomena in pigtail macaques. Neglect was mostly limited to first-born
      and newborn infants. Abuse was more likely to occur in some families than in
      others, and within-abusive families, it was more-likely to occur among closely
      related females than among distantly-related females. Infants whose siblings had
      previously been abused were themselves especially at risk of abuse. Material
      health and infant sex were not risk factors for abuse. CONCLUSIONS: This study
      provides the first evidence of genealogical effects on infant abuse in nonhuman
      primates. Several characteristics of infant abuse in socially living macaques
      suggest that this phenomenon could represent a good animal model for studying the
      etiology of child abuse and neglect.

PMID- 9158907
TI  - Ethnic differences in circumstances of abuse and symptoms of depression and anger
      among sexually abused black and Latino boys.
AB  - OBJECTIVE: The present study was designed to examine the extent to which ethnic
      differences in the circumstances of abuse would be related to psychological
      outcomes and whether the relationship of ethnicity to psychological outcomes
      would be independent of ethnic differences in the circumstances of abuse. METHOD:
      Ethnic difference in the circumstances of the abuse, depression, and anger, as
      measured by the Children's Depression Inventory and the State-Trait Anger
      Expression Inventory, were assessed in 60 Black and Latino sexually abused males
      aged 13 to 18 years. Factors related to levels of depression and anger in these
      two groups were also identified. RESULTS: Latino males were more likely to have
      been sexually abused by an extended family member, experienced more genital
      fondling and were exposed to more sexually abusive behaviors. Blacks were more
      likely to be abused by an immediate family member. Black males had higher anger
      scores than Latino males, but, there were no ethnic differences in depression
      scores. Both ethnicity and the relationship to the perpetrator were significantly
      related to scores on the State-Trait Anger Expression Inventory, however,
      ethnicity was also significantly related to anger scores irrespective of the
      relationship to the perpetrator. CONCLUSIONS: Ethnic differences in the
      circumstances of abuse were related to psychological outcome and the relationship
      of ethnicity to anger scores was independent of ethnic differences in the
      circumstances of abuse.

PMID- 9158908
TI  - The prevalence and nature of child sexual abuse in Queensland, Australia.
AB  - Child sexual abuse is a problem of considerable proportion in the USA and Europe
      (Finkelhor, 1994). However, there are very little data available on child sexual
      abuse in Australia apart from the first ground-breaking study by Goldman and
      Goldman (1988a) undertaken in Victoria. No Australian National or State
      statistics are available. Apart from anecdotal evidence from fragmented sources,
      the prevalence and nature of child sexual abuse in Queensland have not been
      researched. Queensland is considered one of the most politically and socially
      conservative states in Australia, has a hotter climate, and is less developed
      than other Australian states. Just as the USA has its Deep South. Queensland is
      similarly referred to as the "Deep North."

PMID- 9158909
TI  - Sustainable development and child health.

PMID- 9158910
TI  - Diet, smoking and exercise: interrelationships between adolescent health
      behaviours.
AB  - A questionnaire measuring smoking status, exercise and dietary behaviour was
      administered to 932 high school pupils during regular classroom periods. Pupils
      were taken from three year groups which included 327 year 8 (12-13 years), 313
      year 9 (13-14 years) and 292 year 10 (14-15 years). Pupils also indicated whether
      they could recall classroom teaching on 15 food- and health-related issues.
      Scores were derived representing self-reported frequency of eating foods that
      were high in fat, and fresh fruits and vegetables. Smoking was found to be
      associated with lower levels of exercise, consumption of less fresh foods and
      greater consumption of fatty foods. In addition, consumption of fresh foods was
      found to be positively correlated with exercise. These findings have implications
      for the organization of school-based health education efforts and suggest that
      health education programmes need to adopt an integrated approach rather than
      treat health behaviours in isolation from each other.

PMID- 9158911
TI  - Supporting special needs in the mainstream classroom: children's perceptions of
      the adult role.
AB  - Inclusion of children with significant special educational needs within the
      ordinary classroom frequently involves additional human resources. In the UK,
      specialist teachers and classroom assistants (teachers' aides) are now a regular
      feature of many classrooms. Their purpose is to provide advice and support to the
      teacher and/or specifically to assist the child with special educational needs in
      accessing the mainstream curriculum. There has been little research into the
      impact of these additional adults on children not designated as having special
      educational needs, although their attitudes and responses are likely to prove
      critical to the success of any policy of inclusive education. This study examines
      the responses of 713 children (ages 7-14+) attending 27 schools in London to
      questions relating to the role of adults supporting special educational needs
      (SEN) children in their classrooms and to the social desirability of being
      singled out for support. The findings suggest that the majority of those
      responding saw the support being directed towards the teacher's needs. The
      recognition of pupils' needs was less frequently expressed. The desirability of
      support became challenged by some children in the upper age range of the sample.
      Reasons for this and the implications for inclusive education are considered.

PMID- 9158913
TI  - Exploration of surface-textures in congenitally blind infants.
AB  - The haptic exploratory procedures that eight congenitally blind infants aged 8-24
      months used to explore a gradient surface texture were investigated. Exploration
      of the gradient texture was examined over five sessions with 2 weeks between
      sessions, followed after 1 week by a sixth session, in which exploration of the
      gradient texture was compared to exploration of two other textures. Results
      showed that the infants have a wide range of exploratory strategies available and
      that the older infants can use these strategies in a specific manner. Results are
      discussed with reference to current ideas about the exploratory possibilities of
      congenitally blind infants. Use of texture in the stimulation of exploration of
      blind infants is discussed.

PMID- 9158912
TI  - Detection of behavioural and emotional problems in deaf children and adolescents:
      comparison of two rating scales.
AB  - The aim of this study was to establish rates of behavioural and emotional
      problems, and of social maladjustment, in a population of deaf children,
      particularly in relation to different methods of communication. The parents of 84
      children who attended two schools for the deaf took part. They completed the
      parents' checklist (PCL), a behaviour rating scale for deaf children, and the
      Child Behaviour Checklist (CBCL), a measure widely used in the general
      population. The two instruments were significantly correlated on the severity of
      behavioural and emotional problems, but their previously established cut-off
      scores detected different rates of possible clinical cases, i.e. children with
      mental health disorders. According to the CBCL, 40% of children were within the
      clinical range, and 82% were socially dysfunctional compared with the general
      population. The PCL identified a much higher percentage (77%) of caseness.
      Behavioural and emotional problems were significantly higher in Asian children.
      Although all subjects used sign language, the additional use of speech, which may
      indicate increased hearing ability, had a protective effect for adolescents. The
      findings are discussed in relation to the validation of the instruments and the
      development of intervention programmes for deaf children.

PMID- 9158914
TI  - Selective eaters: a retrospective case note study.
AB  - The literature on children who present with selective eating is limited to single
      case studies. This study aims to provide a descriptive clinical profile for these
      children. Case notes of 33 patients between 4 and 14 years of age, seen in two
      clinics over a 4-year-period were studied. Over two-thirds of the cases were
      boys. A significant minority had poor growth or weight gain. The children
      suffered from anxiety, obsessive compulsive symptoms, both food and non-food
      related and often had social and school difficulties. Mealtimes caused immense
      anxiety for family members and frequent mealtime battles was reported by the
      parents of the younger selective eaters, whereas parents of older children seemed
      to have given up trying to change their child's eating habits. A history of
      depression in at least one parent was found in a third of the parental couples.

PMID- 9158915
TI  - The curvature function evolved in scale-space as a representation of biological
      shapes.
AB  - A new and simple approach for calculating the curvature functions of arbitrary
      non-analytical (biological) contours of planar shapes is described. This approach
      does not require either parametrization or the evaluation of derivatives, which
      eliminates sources of error and noise amplification. It is shown that this method
      provides better results than the traditional procedure and the procedure
      employing polar coordinates. The paper describes how to evolve contours in scale
      space, and it is discussed how, due to its invariant properties, curvature
      functions, evolved in scale-space, are suitable as representations of shapes. The
      techniques described are applied to the digitized contours of isolated corneal
      endothelial cells.

PMID- 9158916
TI  - Correlation between source asymmetry and scalp potential asymmetry in a prolate
      spheroid model of the head.
AB  - The correlation between electric source asymmetry in the brain and potential
      amplitude asymmetry developed on the scalp was investigated using a computerized
      analytical prolate spheroid model of the head. The source was modeled by a single
      current dipole located in the occipital region of the brain. The potential
      created by the dipole was calculated using Laplace's equation with boundary
      conditions while allowing a quasi-static formulation and linear media. The dipole
      was located in the inner part of a four-compartment medium representing the
      scalp, the skull (with non-isotropic conduction), the cerebrospinal fluid (CSF),
      and the cortex. The asymmetry was modeled by a dipole located with an angle to
      the major axis connecting the nasion and the inion. The present study shows that
      source asymmetry can cause non-negligible asymmetries in the potential amplitude
      measured on the scalp above homotopic points of the two hemispheres. A potential
      asymmetry of up to 15% in the O1-O2 pair of electrodes was found when the dipole
      is rotated from the symmetric major axis at an angle of 10 degrees. The source
      asymmetry in the occipital region can be related to falx deviation, which is an
      asymmetry present in the majority of the population. Since this asymmetry is not
      related to real physiologic and psychologic sources of potential amplitude
      asymmetries, it should be taken under consideration when potential distribution
      analysis is performed.

PMID- 9158917
TI  - Distributed system for processing 3D medical images.
AB  - Three-dimensional (3D) image data generated by radiological imaging modalities
      such as CT and MRI can provide detailed structural insight. Automating the
      analysis of these images can improve the consistency of the results and reduce
      user interaction time, but introduces a tremendous computational burden. To
      address this problem, we have designed a distributed processing environment for
      the rapid processing of 3D medical images. Our system allows a user to perform
      automatic 3D filtering, segmentation, and measurement on a 3D image using a
      heterogeneous network of processors and the PVM protocol.

PMID- 9158918
TI  - A comparison of volume conductor effects on body surface Laplacian and potential
      ECGS: a model study.
AB  - The objective of this investigation is to study, using a computer model, the
      torso volume conductor effects on body surface potential electrograms and body
      surface Laplacian electrograms. A spherical volume conductor model was used to
      approximate the torso and the heart. Myocardial electrical events were
      approximated by two distributed dipole-layers representing activation wavefronts
      propagating from the endocardium to the epicardium. The present computer
      simulation results indicate that the body surface Laplacian maps provide enhanced
      performance over the body surface potential maps in resolving the configurations
      of two activation wavefronts over the anterior wall of the heart.

PMID- 9158919
TI  - An automated system for analysis and interpretation of epileptiform activity in
      the EEG.
AB  - Electroencephalography is an important clinical tool for the evaluation and
      treatment of neurophysiological disorders related to epilepsy. However, the
      analysis and interpretation of the electroencephalogram (EEG) is not an easy task
      due to the variety of waveforms that are possible. Consequently, EEG analysis is
      in need of an objective and quantitative methodology. In this paper, an automated
      system for diagnosing epilepsy is presented. The system combines both the
      electrocerebral activity related to epilepsy resulting from EEG and other
      neurophysiological expertise, mainly based on clinical symptoms that occur during
      the patient's clinical attack, to avoid misdiagnosis. The system consists of two
      major stages. The first is a feature extractor in which half-waves are detected
      and artefacts are eliminated. The second and most important stage is a knowledge
      based system for recognising and classifying epileptiform events. In particular,
      the analysis is based on the detected EEG patterns representing epileptiform
      activity, localization information of discharge focus and clinical symptoms. Once
      a diagnosis is established, the system also proposes a therapy. The proposed
      system has been tested using many different clinical cases, and the obtained
      experimental results are acceptable.

PMID- 9158920
TI  - Left ventricular pressure and volume data acquisition and analysis using LabVIEW.
AB  - To automate analysis of left ventricular pressure-volume data, we used LabVIEW to
      create applications that digitize and display data recorded from conductance and
      manometric catheters. Applications separate data into cardiac cycles, calculate
      parallel conductance, and calculate indices of left ventricular function,
      including end-systolic elastance, preload-recruitable stroke work, stroke volume,
      ejection fraction, stroke work, maximum and minimum derivative of ventricular
      pressure, heart rate, indices of relaxation, peak filling rate, and ventricular
      chamber stiffness. Pressure-volume loops can be graphically displayed. These
      analyses are exported to a text-file. These applications have simplified and
      automated the process of evaluating ventricular function.

PMID- 9158921
TI  - A comparison of similarity measures for digital subtraction radiography.
AB  - Subtraction is useful in detecting small changes in sequentially acquired
      radiographs. Even if the imaging geometry is constant, radiographs must be
      registered after their digitization. To compare different algorithms for image
      registration and to register digital X-rays themselves, various similarity
      measures have been proposed. This study compares eight mathematical similarity
      standards using 172 radiographs acquired in different, but exactly known
      projection. Whenever the computation time is a critical factor, e.g. registering
      images using methods similar to correlation techniques, the entropy of the
      subtraction image's histogram function (EHDI) is found to be the best similarity
      standard. If not, e.g. comparative assessing different image registration
      techniques, the cross covariance coefficient (CCC) is appropriate.

PMID- 9158922
TI  - Applying local statistics to detect subtle G-bands in chromosomes.
AB  - Genetic disorders manifested in chromosome aberrations can be evaluated by
      analysis of the banding pattern of human metaphase chromosomes. We describe the
      resolution of chromosomal bands depending on the degree of chromosomal
      condensation and introduce a pattern enhancement technique using local statistics
      to improve band pattern features of a past condensation stage. The algorithm was
      first tested on synthesized profiles to determine its characteristics as the
      parameters of the algorithm are varied. It is shown that the method is capable of
      enhancing subtle staining patterns hidden in artificial profiles as well as in
      measured profiles. The example of a human chromosome No. 11 demonstrates the
      importance of the described technique for chromosome classification in ambiguous
      cases.

PMID- 9158923
TI  - Extrahepatic immunologic features of chronic viral hepatitis.
AB  - Patients with chronic viral hepatitis commonly have immunologic manifestations,
      including autoantibodies and concurrent immune diseases. These immunologic
      findings may resemble those of autoimmune hepatitis and they are not disease
      specific. High titer autoantibodies (titers > or = 1:320) are uncommon in chronic
      viral hepatitis as are multiple concurrent autoantibodies. These findings reflect
      an autoimmune-predominant disorder in which the viral infection may be
      coincidental or facilitative. Concurrent immunologic disorders may be viral
      antigen-driven and associated with immune complex deposition (cryoglobulinemia,
      glomerulonephritis, cutaneous vasculitis, and polyarteritis) or autoantigen
      driven (autoimmune thyroiditis and Sjogren's syndrome) and associated with host
      rather than virus-specific factors. Genetic predispositions influence immunologic
      expression. Seropositivity for antinuclear antibodies is associated with HLA A1
      B8-DR3, and concurrent immunologic diseases are associated with the DR4 allele.
      Interferon therapy is appropriate for patients with viral antigen-driven
      processes that depend on immune complex deposition and for patients with mild
      background autoimmune expressions. Corticosteroid therapy should be considered
      for those unusual patients with predominant autoantigen-driven processes since
      interferon treatment may exacerbate immune-mediated diseases. Patients with
      chronic hepatitis B and C can have similar immune features, but patients with
      chronic hepatitis C more commonly have autoantigen-driven processes.

PMID- 9158924
TI  - Eicosanoids and the esophagus.
AB  - Eicosanoids are metabolites of arachidonic acid and include, among other
      compounds, the prostaglandins and leukotrienes. These metabolites are known to
      play important roles in the health and disease of many gastrointestinal tissues.
      Less attention, however, has been given to their functions in the esophagus. The
      present study, therefore, aims both to review the current knowledge about
      eicosanoids in healthy and diseased esophagi, and to critically assess the data
      pertaining to their role in the pathophysiology of gastroesophageal reflux
      disease.

PMID- 9158925
TI  - Amyloid and the gut.
AB  - The systemic amyloidoses are serious and potentially fatal disorders caused by
      deposition of autologous proteins in an abnormal fibrillar from. The clinical
      features are highly variable but gut involvement is common and random
      gastrointestinal biopsies are diagnostic in 80% of patients. Presentations
      include macroglossia, motility disorders, hemorrhage and pseudo-tumors, although
      amyloid can mimic almost any other gut pathology. Nonspecific mucosal
      abnormalities are common both radiologically and at endoscopy. Scintigraphy with
      serum amyloid P component demonstrates and quantifies the systemic amyloid
      deposits. Therapy that reduces the supply of the amyloid fibril precursor protein
      can markedly improve prognosis. Intensive nutritional support for malnourished
      patients, motility-enhancing drugs and octretide for motility disorders, and
      correction of clotting disorders in bleeding patients are important adjunctive
      treatments.

PMID- 9158927
TI  - The home as a framework for health care.
AB  - The past two or three decades have witnessed a steep rise in the cost of health
      and social services. It is anticipated that this uphill climb will continue and
      bring these systems to a complete collapse within a few decades. The prevention
      of this crisis depends on the elimination of some of the causes of the rise: (a)
      we do not want to save costs by sacrificing the quality of our services; (b) we
      have no control over the quantity of clients utilizing these services, or the
      seriousness of their problems; (c) we can, however, replace part of the expensive
      institutional care by the more natural and cost-effective home care, supplied by
      volunteers, strengthened by human and technological services. These principles
      guided an Israeli organization called Yad Sarah, whose leadership in the supply
      of home and community care enables thousands of ill, elderly and disabled people
      to remain at home and thus save the high cost of institutionalization.

PMID- 9158926
TI  - Ileo-anal pouch function and dysfunction.
AB  - Ileal pouch-anal anastomosis (IPAA) has become well established as the ideal
      surgical option for the majority of patients with chronic ulcerative colitis.
      Improvements and simplifications in operative technique over recent years mean
      that such patients need no longer live with the fear of a permanent ileostomy
      with its associated physical, sexual and sometimes psychological problems. Most
      patients who have undergone IPAA achieve a good quality of life. There are,
      however, a number of questions with regard to the ileal pouch that remain
      unanswered. The purpose of this review is to summarize the advantages and
      disadvantages of the various designs of pouch which have been described, to
      discuss the function of the normal pouch and manifestations of dysfunctional
      pouches.

PMID- 9158928
TI  - The elderly: the single greatest achievement of mankind.
AB  - The single greatest achievement of mankind is very likely the increase in life
      expectancy which has occurred in the twentieth century. Coupled with a decline in
      the birth rate worldwide, the mean age of most nations is rapidly increasing and
      the old (especially the old-old, those 80 years of age and over) represent an
      increasing percentage of the dependent population of the world. Although the
      ageing of the population will have ramifications for almost all aspects of
      society, those concerned with the provision of health care are especially
      affected. With chronic disease replacing acute illness, and costs of care
      mounting, health-care providers will require a comprehensive assessment of its
      older citizens so as to be able to provide cost-effective care across all sites,
      be that location a hospital or, more frequently, the home. The development of
      such capabilities is already under way by the InterRA1 group, an international
      group of investigators.

PMID- 9158929
TI  - Home hospitalization in the spectrum of community geriatric care.
AB  - The Home Hospitalization Programme was initiated in Jerusalem in 1991 to provide
      intensive medical care at home in order to prevent or shorten hospitalizations.
      The programme was based upon regular home visits by physicians, and nursing
      assessment to determine the need for regular nursing care. Primary-care
      physicians and nurses were renumerated by a global monthly fee, and were on 24-h
      call in addition to their periodic visits. Patients were recruited by senior
      geriatric physicians from acute hospital wards, as well as from the community, at
      the family doctor's request. Ancillary services available to the home
      hospitalization team included laboratory and electrocardiographic testing,
      specialty consultations, physical occupational or speech therapy, social work and
      home help up to 3 h daily. Monthly visits by a senior physician provided
      oversight and further consultation. Home hospitalization grew out of the
      continuing care division of the Clalit Sick Fund, a health maintenance
      organization providing umbrella medical insurance and ambulatory care. The
      programme grew synergistically with the other facilities of continuing care to
      encompass a network of comprehensive services to acute, subacute and chronic
      patients both at home and in institutional settings. In 4 years this network
      succeeded in establishing the focus of subacute intensive care in the community,
      achieving high levels of patient and family satisfaction, as well as striking
      economic advantages. In its first 2 years of operation home hospitalization saved
      S4 million due to reduced hospital utilization, and preliminary data for the
      subsequent 2 years indicated that this trend continued. Home hospitalization
      became the hub of a far-reaching system of supportive, intensive and humane care
      in the community.

PMID- 9158930
TI  - New challenges in ageing: home care.
AB  - Most nations are undergoing two fundamental demographic changes: concentration of
      their population in cities and accelerated pace of population ageing. The fastest
      growing population is that 85 years and over. Morbidity increases with advancing
      age, functional capacities decrease; this results in decreased performance of
      activities of daily liver and need for services. The challenge is particularly
      strong in urban areas. Modern societies seek solutions in maintaining the elderly
      in their homes through home care programmes for those who are functionally
      impaired, homebound, and need support in home-making and home nursing. Home care
      is firmly established in programmes for the elderly. In order to become a
      scientific discipline home care has to define its boundaries, identify clients by
      careful multidisciplinary assessment, provide answers regarding its cost
      effectiveness, evaluate outcomes of home caring develop indicators of high
      quality care and advise appropriate home care technology, which is affordable and
      accessible. Home care for the elderly population living in remote rural areas is
      one of the future challenges.

PMID- 9158931
TI  - The importance of the community and its resources.
AB  - This paper examines the concept of community, and defines it in terms of
      boundaries, shared needs and social interaction. It considers types of community
      and the functions they perform. After discussing different community resources
      the paper concentrates on the resources of authority and legitimation, which may
      be achieved by the use of client involvement and general community
      representation. An empiric test of the connection between client representation
      and effectiveness is used to illustrate the value of involving clients, their
      families and other community representatives is community services such as home
      care.

PMID- 9158932
TI  - New developments and issues in home care policies.
AB  - This paper provides an overview of the major trends in the organization of
      services for the disabled elderly, and the implications for the elderly of the
      emphasis in recent years on remaining at home in the community. The paper
      presents an example of changing policies from the experience of Israel, which
      recently enacted a Community Long-term Care Insurance Law to increase levels of
      home care entitlements to the severely disabled.

PMID- 9158933
TI  - Home care, medical care and the new competitive environment.
AB  - Health-care organization and financing is rapidly changing in the USA due to
      competitive pressures. Parallel changes are occurring in other countries. These
      changes are affecting, and will affect, home care services. Watching these
      changes, and building on social models, leads one to focus on important
      developments. These developments include: point of service plans, disease
      management, outcomes measurement, price and quality competition. These changes
      will make measured outcomes and demonstrated value essential in home care.

PMID- 9158934
TI  - Community-based care: back to the future!
AB  - Home- and community-based care are deeply rooted in the United States and
      worldwide. Public and private organizations have provided formal in-home and
      community health services for more than a century. Today they are an integral
      part of the care continuum, ranging from highly technical and professional
      services to simple forms of non-professional and voluntary support in homes.
      Because the roles and functions of community workers have expanded and
      diversified, organizations must successfully recruit, train and support workers
      with widely differing skills. In health care's new economic era, health has re
      emerged as a community rather than individual concern. Non-traditional models of
      service delivery will be the cornerstone of community-based health care.
      Providers and policy-makers must find new ways to refocus from treating illness
      to achieving and maintaining health.

PMID- 9158935
TI  - The patient and family adjustment to chronic disease in the home.
AB  - The increase in chronic disease with shortened hospitalizations has led to an
      increase in home care, with added adjustment problems for patients and their
      families. The majority of families cope satisfactorily, although most have
      periods of instability or difficulties which require appropriate support. In
      considering the impact of chronic illness, cognizance must be taken of the
      patient, the illness, the caregiving system, the medical care system, the
      interrelationship between them and the effect of the environment on all of them.
      The adjustment to chronic illness depends on the complementary meshing of the
      life and time cycles of the above factors during the alternating periods of
      crises and chronic maintenance. It is apparent that, in a pluralistic
      multicultural society, a broad range of diverse family forms and functioning is
      compatible with adjustment to a member with chronic disease. Finally, a scheme
      for the medical team's assessment and care is presented.

PMID- 9158937
TI  - Foulds' dangerous idea revisited: the multistep development of tumors 40 years
      later.

PMID- 9158938
TI  - Retroviruses and retroelements in diseases and in gene therapy.

PMID- 9158939
TI  - Genetically modified tumour vaccines carrying inserted genes for immunoregulatory
      molecules.

PMID- 9158940
TI  - Cytokine-based gene therapy of human tumors. An overview.
AB  - This review first summarizes the different strategies of gene therapy of cancer
      and then focuses on the immunological approach. Several studies in animal models
      with cytokine gene-transduced tumor cells indicate that local cytokine release
      usually results in tumor growth inhibition. Moreover, in a number of cases
      vaccination with such cells can reduce growth of established tumors or even cure
      the tumor-bearing animals. Translation of such a principle in human clinical
      setting is reported. We have transduced human melanoma cells with genes coding
      for interleukin (IL)-2, IL-4 or B7-1 and characterized such lines. The phenotype
      did not change after gene insertion but the functional, immunostimulatory
      activity of IL-2 or B7-1 gene-transduced melanoma cells was significantly
      increased compared to that of parental lines. These-lines were then used to
      vaccinate melanoma patients. Preliminary results of trials with IL-2 gene
      transduced cells are presented which indicate a weak clinical response and the
      activation of a melanoma-specific cytotoxic T lymphocyte response in a low
      percentage of patients.

PMID- 9158941
TI  - Fluorescence in situ hybridization (FISH) in cytogenetics of leukemia.
AB  - The principle of the fluorescence in situ hybridization (FISH) method is in the
      base pairing of the DNA probe to complementary sequences in the studied specimen.
      The hybridization of specific DNA or RNA probes to the cellular targets attached
      to the microscopic slides is widely used for the identification of chromosomal
      translocations, deletions, amplifications of specific genes, and chromosome
      number changes in mitotic and/or interphase cells. The use of FISH with the
      modifications of the basic method meant a breakthrough in detection and diagnosis
      of human malignancies. During the last tow years FISH was used in our laboratory
      for: (a) identification of constitutive and acquired numerical and structural
      chromosomal abnormalities; (b) detection of minimal residual disease or early
      relapse in patients treated for leukemia by bone marrow transplantation (BMT)
      and/or chemotherapy; (c) determination of the cytogenetic pattern of non-dividing
      or terminally differentiated cells. To confirm the structural rearrangements
      found by the classical G-banding technique, the whole chromosome painting probes
      which hybridize to multiple chromosomal sequences were used. The alpha-satellite
      DNA probes which detect centromeric repetitive sequences were utilized for
      determining the numerical and sex chromosome changes. Specific unique chromosomal
      sequences which can confirm all chromosomal rearrangements, i.e., deletions,
      translocations or inversions with the corresponding breakpoints were introduced
      for specific cases. Recently, every chromosomal translocation, deletion and any
      other structural or numerical change found by conventional cytogenetic analysis
      in the bone marrow cells of the patients with leukemia has been verified in our
      laboratory by FISH. The results of this study showed that FISH is more efficient
      than conventional cytogenetics in detecting residual malignant cells. For
      chromosomal rearrangements FISH is an extremely sensitive method which not only
      verifies but also interprets with more precision the findings of classical
      cytogenetics.

PMID- 9158942
TI  - In Memoriam. Flowers for George D. Snell (1903-1996).

PMID- 9158943
TI  - Negative regulation of the alpha-foetoprotein gene in fibroblasts: identification
      and characterization of cis and trans elements.
AB  - The alpha-foetoprotein (AFP) gene is extinguished in hybrids formed between
      hepatoma cells (expressing cells) and fibroblasts (non-expressing cells).
      Transfection experiments with constructions containing segments from the promoter
      region of the AFP-gene, placed upstream of an ubiquitously expressed promoter
      (the Herpes virus thymidine kinase gene promoter), showed that the AFP gene
      derived sequence contains at least one negative element active in fibroblasts
      (while this sequence behaves as an enhancer in hepatoma cells). We identified
      such a fibroblast negative region, localized between nucleotide positions -80 to 
      38 (FNE1). Gel retardation experiments showed that FNE1 specifically binds
      fibroblast nuclear proteins, generating three complexes. The sequence from -57 to
      -43 was shown to be responsible for both the formation of these complexes and the
      negative activity of FNE1. These results suggest that the binding of nuclear
      factors to the AFP promoter region contributes to silencing the AFP gene in non
      expressing cells, such as fibroblasts, and thus to establishing lineage-specific
      expression of the AFP gene.

PMID- 9158944
TI  - Flow cytometric analysis of lymphocytes isolated from nasal polyps.
AB  - We analyzed by flow cytometry the expression of IL-2 receptors (alpha subunit
      CD25) and ICAM-1 adhesion molecules (CD54) on T cells and subsets (CD4, CD8)
      isolated from nasal polyp tissue in allergic and non-allergic patients. We found
      a significant increase in IL-2 receptor and ICAM-1 molecule expression on T cells
      isolated from nasal polyp tissue compared to peripheral blood lymphocytes. We
      also found a significantly increased expression of ICAM-1 molecules on CD8+ cells
      in non-allergic compared to allergic patients. The latter may reflect a
      difference in cytotoxic immune response between allergic and non-allergic
      patients, but the result should be confirmed in a more extensive study including
      cytokine and immunoglobulin analysis. We hope that it would enable us to obtain a
      deeper insight into the local immune events and further to clarify the etiology
      and pathogenesis of nasal polyps and their relation to allergy.

PMID- 9158945
TI  - Genotoxicity of N-nitroso-N-methylurea and acetone oxime in the transgenic
      Drosophila carrying the human gene encoding a subunit of glutathione S
      transferase.
AB  - The genotoxic effects of N-nitroso-N-methylurea (MNU) and acetone oxime (ACOX)
      were tested in the Somatic Mutation and Recombination Test (SMART) in Drosophila
      melanogaster. We have performed the same assay on transgenic flies expressing the
      human gene encoding a glutathione S-transferase alpha subunit (HGST). The SMART
      assay is used here to demonstrate genotoxicity and to determine the effect of
      human glutathione S-transferase on the genotoxic response. Three types of
      Drosophila strains were used: non-transgenic strains first described by Szabad
      (1986), transgenic strains derived from the Szabad strains but expressing the
      bacterial lacZ gene, and similarly derived transgenic strains expressing the HGST
      gene. MNU was highly genotoxic in both transgenic and non-transgenic flies. The
      non-transgenic lies were significantly more sensitive to the genotoxic effects of
      MNU compared to both types of transgenic flies. There were statistically
      significant differences between the transgenic HGST crosses and transgenic lacZ
      and non-transgenic control crosses but there was no significant difference
      between the genotoxic response to MNU in flies from the transgenic cross with
      lacZ and from the cross carrying three copies of HGST. ACOX also proved to be
      genotoxic to both non-transgenic and transgenic flies. However, flies carrying
      three copies of the gene were significantly more resistant to the genotoxic
      effect of ACOX than those transgenic flies with two or no copies of the human
      gene.

PMID- 9158947
TI  - Changes in macrophage function during chemotherapy.
AB  - Antibiotics, in addition to killing or inhibiting the growth of microorganisms,
      may also affect the mechanism of host defence in many ways. Such effects may be
      clinically relevant especially in the case where an impairment of immunological
      function can be seen. We, therefore, decided to study the influence of penicillin
      G, cefotaxim, ceftazidime, streptomycin, and lincomycin on the function of
      phagocytes by using the macrophage adherence assay and the macrophage spreading
      assay. We also followed the concentrations of neopterin and interferon gamma (IFN
      gamma) in the plasma of mice treated with the above mentioned antibiotics.
      Changes in adherence of peritoneal macrophages were seen in mice treated with
      therapeutic doses of penicillin G and cefotaxim, after 2 h of incubation.
      Cefotaxim and streptomycin in the usual therapeutic dose and ceftazidime in a
      fourfold higher dose influenced the capacity of peritoneal macrophages to spread
      on a glass surface. The same was seen with lincomycin when administered in the
      therapeutic dose and in a fourfold higher dose. In all the mice treated with
      antibiotics the concentration of IFN gamma was higher than in the control mice,
      while the reverse was seen concerning neopterin release, with an exception in
      mice treated with streptomycin.

PMID- 9158946
TI  - Treatment of transplanted spontaneous rat T-cell leukaemia with local
      administration of recombinant murine interleukin-2.
AB  - Spontaneous rat CD4+CD8-T-cell leukaemia transplanted in syngeneic recipients
      served as an experimental model system for IL-2 therapy. As a source of IL-2,
      supernatants from in vitro cultured plasmacytoma cell line X63-m-IL2 secreting
      constitutively recombinant murine IL-2 were utilized. Administration of IL-2,
      s.c. to the vicinity of the tumour inoculum, suppressed tumour growth. The tumour
      inhibitory IL-2 effects were time- and dose-dependent. When the treatment has
      started 10 days after the challenge with 10(4) leukaemia cells, IL-2 inhibitory
      effects on the lymphoma growth in situ were demonstrated by lower tumour weight
      combined with necrotic changes. No histological signs of lymphoma generalization
      were found in parenchymatous organs of IL-2-treated rats in contrast to the
      untreated controls. No histological or functional injuries to the kidneys due to
      IL-2 administration were found. The results of effector cell phenotyping
      demonstrated the kinetics of the CD4+/CD8+ ratio characterized by CD4+ T-cell
      depletion and resulting increase in the percentage of CD8+ PBL.

PMID- 9158948
TI  - Recombinant interleukin-2 acts as an adjuvant and helps to increase the efficacy
      of tumour vaccines.
AB  - To examine augmentation of the resistance-inducing effect of tumour vaccines with
      IL-2, we have used the cytokine produced by genetically modified somatic cells,
      and a conventional experimental model of TRA-expressing, MC-induced murine
      fibrosarcoma transplanted in histocompatible mice. We have found that the effect
      of s.c. immunization with irradiated tumour vaccines can be substantially
      enhanced by IL-2 injected repeatedly at the site of vaccination. To investigate
      the kinetics of local and systemic immunocyte populations during the course of
      immunization with vaccine plus IL-2, some of the vaccinated mice were sacrificed
      and their regional LNC and spleen cells were used for phenotypic analysis. It has
      been found that local (s.c.) administration of the irradiated tumour vaccine plus
      IL-2 was accompanied by an early depletion of CD4+ and CD8+ cells in regional
      lymph nodes followed by subsequent rebound lymphocytosis. The local reaction was
      followed by a systemic response in the spleen characterized with an increase in
      TCR alpha beta + CD4+ lymphocytes.

PMID- 9158949
TI  - Putative regulatory sequence in human papillomavirus type 16 E2 open reading
      frame.
AB  - A 114 bp fragment of the human papillomavirus type 16 (HPV16) E2 open reading
      frame (nt. 3142-3255) containing a putative estrogen responsive element (ERE) was
      amplified and cloned into pBLCAT2 plasmid in both sense (p159-4) and anti-sense
      (p164) orientation. The plasmids were transfected into human breast-cancer cell
      line MCF-7 containing estrogen receptor and the cultures were kept in the
      presence or absence of beta-estradiol. The chloramphenicol acetyltransferase
      (CAT) activity was not influenced by estrogen. However, a silencer effect was
      observed both in cultures transfected with p159-4 and p164 plasmids. We prepared
      and cloned synthetic fragments containing the putative ERE and failed to prove
      that the palindrome in the putative ERE was responsible for the silencer
      activity.

PMID- 9158950
TI  - CTLL assay: comparison of two methods for IL-2 determination.
AB  - Two different modifications of CTLL techniques for IL-2 detection, the routine
      3II-thymidine incorporation assay and the colorimetric MTT method, were compared.
      The reproducible results of the studies of supernatants from in vitro propagated
      transfected cells were obtained. The employed methods appeared to be comparable
      and are used simultaneously in our co-operating laboratories for estimation of
      the levels of IL-2 secreted by the transfectants that are applied as the source
      of the cytokine in therapeutic experiments.

PMID- 9158951
TI  - Epitope analysis of the human p53 tumour suppressor protein.
AB  - Using a set of overlapping peptides of the human p53 protein, we have performed
      an accurate mapping of the p53 antigenic sites, recognized by a panel of 19
      monoclonal antibodies from the Bp53 series. The results show that most of the
      antibodies recognize determinants localized in the amino-terminal domain of the
      protein. Several antibodies reacted with peptides which correspond to the
      antigenic determinants localized in the carboxy terminus of p53. None of these
      antibodies reacted with peptides in the central DNA-binding domain of p53
      protein.

PMID- 9158952
TI  - Factors influencing the preimmune antibody repertoire.
AB  - Preimmune antibody repertoire is not a statistical representation of all germ
      line VH, D, JH and VL, JL segments encoding heavy and light chains, respectively.
      The antibody repertoire is biased towards a fraction of VH and VL gene segments
      in fetal/neonatal as well as adult life. The repertoire bias starts at the
      surface Ig-negative pre-B cells and persists throughout B-cell ontogeny. Antigen
      independent processes like preferential rearrangements of VH, D and JH segments
      and pairing of the heavy and surrogate light chain operate at the surface Ig
      negative pre-B cell stage. Subsequently B cells may be subject to self-antigen
      selection based on the specificity of their surface receptors.

PMID- 9158953
TI  - Production of env-deficient rous sarcoma virus (RSV) early after infection.
AB  - Production of defective virus particles during the early stage of Rous sarcoma
      virus (RSV) infection of chicken embryo fibroblasts (CEF) was examined. RSV
      harvested 2 days post infection (2pi) had 10 to 30 times lower specific
      infectivity (focus forming units/unit reverse transcriptase activity) than 5pi
      harvest. Virus particles produced on day 2 contained less env proteins than
      particles harvested on day 5. The amount of other viral proteins was equal in
      particles harvested on day 2 and day 5. Analysis of infected cells revealed that
      these cells synthesized less env proteins on day 2 than on day 5. RSV RNA in
      infected cells was spliced normally on day 2. Infection at a low multiplicity of
      infection (moi) prolonged the production of defective particles. When infection
      was initiated by a low moi (0.01), particles harvested on day 5 had the same
      characteristics as 2pi particles after infection with a high moi (1.0). We
      conclude that the low infectivity of early harvest is due to the reduced amount
      of env proteins in virus particles, which is a consequence of the reduced env
      protein synthesis.

PMID- 9158954
TI  - Drosophila melanogaster, Vicia faba and Arabidopsis thaliana short-term bioassays
      in genotoxicity evaluation of air and soil samples from sites surrounding two
      industrial factories in the Czech Republic.
AB  - The Somatic Mutation and Recombination Test (SMART) in wing cells of Drosophila
      melanogaster, the Vicia faba cytogenetic tests-Sister Chromatid Exchange (SCE)
      and Micronucleus Test (MN), and the Muller test for gametic mutations in
      Arabidopsis thaliana were used for genotoxicity testing of environmental samples
      of pollutants from the surroundings of LACHEMA chemical factory (Brno, Czech
      Republic) and DEZA factory in Valasske Mezirici (Moravia, Czech Republic). Tested
      soil and air samples were taken from the near vicinity of both factories. The
      surroundings of both sites are heavy loaded by exhalation of chemicals from the
      factories. Chemical analyses of the 16 Polycyclic Aromatic Hydrocarbons (PAHs)
      according to the United States Environmental Protection Agency (US EPA) list of
      priority pollutants and heavy metals were performed in both soil and air samples.
      The Drosophila wing spot test was positive in 70.6% of the tested samples, the
      Vicia sister chromatid exchange test in 62.5%, and the Arabidopsis Muller test in
      58.9%. The micronucleus Vicia faba test was quite insensitive in tested
      environmental samples. The concordance between SMART and SCE was 62.5%, between
      SMART and Muller test 76.5%, and between Muller test and SCE 100%. Total
      concordance of these three tests was 79.7%. Muller test for gametic mutation in
      Arabidopsis thaliana and cytogenetic SCE test in Vicia faba seem to be quite
      sensitive and convenient plant bioassays for assessing the mutagenic potential of
      environmental agents, when compared to the SMART test in Drosophila melanogaster.

PMID- 9158955
TI  - The cell cycle positions influence DNA migration as measured with the alkaline
      comet assay in stimulated human lymphocytes.
AB  - Virtually any eukaryotic cell can be processed for analysis of DNA damage using
      the comet assay. The most commonly examined human cells are lymphocyte
      populations. However, many parameters can affect the response of lymphocytes to
      the assay in terms of the ability to detect damage. The response of cultivated
      lymphocytes in the comet assay indicated cycle-dependent differences. The cell
      cycle position has been shown to affect the results obtained using both the
      alkaline and neutral assays. This is primarily a reflection of the complications
      of including S-phase DNA. In the alkaline assay, replicating structures are
      interpreted as strand breaks when denatured, increasing the level of detectable
      damage. We performed the alkaline comet assay to detect differences in the extent
      of DNA in stimulated human lymphocytes collected at different sample times after
      mitogen stimulation. Our results clearly indicate that proliferating lymphocytes
      have a greater migration of DNA (measured with the comet assay as DNA damage)
      than quiescent lymphocytes. The lymphocytes collected at 36, 42, and 48 h after
      mitogen stimulation showed a significantly increased extent of DNA migration in
      comparison to the lymphocytes collected at 0 and 24 h after stimulation. It,
      probably, can be explained by the higher frequency of the S phase cells in
      lymphocyte populations collected at 36, 42, and 48 h. Sites of active DNA
      replication during the S phase behave like single-strand breaks when denatured in
      alkali, and their presence may result in a significant increase of the tail
      moments in S phase cells.

PMID- 9158957
TI  - Variability of the adaptive response to low dose radiation in peripheral blood
      lymphocytes of twins and unrelated donors.
AB  - To assess the genetic control of the induction of the adaptive response after low
      dose ionizing radiation, the frequencies of chromosome aberrations were evaluated
      in four pairs of monozygotic twins, two pairs of dizygotic twins, and in nine
      unrelated individuals. Stimulated cells were exposed to adaptive dose of 5 cGy
      gamma rays at 24 h and challenge dose of 150 cGy gamma rays at 42 h. Cells were
      fixed at 48 h and chromatid and isochromatid breaks were evaluated. The adaptive
      response was found in two pairs of monozygotic twins, but not in the two other
      pairs. Individual differences in adaptive response between the members of
      monozygotic twins were very small. In contrast, the variability in the adaptive
      response between the members of dizygotic twins was much greater and was similar
      to that observed in the unrelated donors. The results confirmed that
      heterogeneity in the adaptive response after exposure to low-dose gamma rays was
      controlled genetically to a considerable extent.

PMID- 9158956
TI  - Relationships between the structure, cytotoxicity and hydrophobicity of
      quinazoline derivatives by quantitative structure-activity relationship.
AB  - Cytotoxicities of 93 quinazoline derivatives against HeLa cells have been
      determined as the isoeffective concentrations inhibiting, after a single dose,
      the protein synthesis to 50% of the control amount after 48 h incubation. The
      dependence of cytotoxicity on hydrophobicity of the studied derivatives has been
      described using a previously published model-based approach. The studied
      derivatives are classified into nine classes each forming a smooth hydrophobicity
      cytotoxicity curve. Owing to the acceptable agreement between the model and the
      data it can be inferred that: (1) the compounds except two derivatives bind to
      the receptors with approximately the same affinity; (2) the criterion for the
      classification is the different rate of metabolism. The results represent a basis
      for a rational development of more potent quinazoline derivatives.

PMID- 9158959
TI  - Two specific and simple methods for genotyping of the paraoxonase/arylesterase
      A/B polymorphism.
AB  - We developed an amplification refractory mutation system (ARMS) and mutagenically
      separated PCR (MS-PCR) assays for genotyping of the paraoxonase/arylesterase
      (PONA) A/B polymorphism as practical, reliable, and more economic alternatives to
      the conventional restriction fragment length polymorphism (RFLP) technique for
      detection of this mutation.

PMID- 9158958
TI  - Cut out or poke in--the key to the world of single genes: laser micromanipulation
      as a valuable tool on the look-out for the origin of disease.
AB  - The optical micromanipulation systems UV(ultraviolet)-Laser Microbeam and Optical
      Tweezers Trap, already proven to be powerful tools for 'non-contact' micro
      manipulation of gametes, cells and organelles, have now made their way into the
      nanocosmos of genes and molecules. Force measurements of DNA transcription have
      been performed and selective DNA molecule micromanipulation gives insight into
      single molecule behaviour. Retrievement of selected single cells without
      contamination is an import prerequisite for further processing with modern
      methods of molecular biology. Laser micro-dissection allows to precisely
      eliminate any unwanted material or to isolate pieces of chromosomes or single
      cells of interest with high accuracy and efficiency. This enables the cell or
      chromosome specific molecular analysis of genes and genetic defects underlying
      disease, such as cancer or infection. This review article gives an overview of
      current topics of laser microbeam application in biological or medical research
      and advanced molecular diagnosis.

PMID- 9158960
TI  - The use of cloned repetitive sequences as hybridization competitors to detect
      single copy sequences.
AB  - To suppress background hybridization due to repetitive sequence elements,
      competitor Alu containing clones were isolated from a subclone library of human
      cosmid clone hP3.1. Pre-annealing of the probe-with this competitor increased the
      signal well above background. In comparison, the addition of the competitor
      directly to both the prehybridization and hybridization solution was more
      effective in reducing background. This dramatically increased the signal to noise
      ratio of the specific hybridization event. Application to fluorescent in situ
      hybridization (FISH) is readily apparent.

PMID- 9158961
TI  - Mitochondrial DNA mutations in Japanese detected by polymerase chain reaction-
      restriction fragment--single strand conformation polymorphism analysis.
AB  - PCR-restriction fragment-SSCP (PCR-RF-SSCP) analysis of mitochondrial DNA by
      HhaI/HincII in Japanese revealed 46 polymorphic patterns. The determinations of
      nucleotide sequence of these 46 patterns revealed 56 mutations compared with the
      Cambridge Sequence.

PMID- 9158962
TI  - A micro-dissection approach for isolation of NotI linking clones from regions
      frequently deleted in RCC and SCLC.
AB  - We demonstrate that micro-dissection can be used for isolating NotI linking
      clones from the human 3p21-pter region. This approach is an improvement to
      positional cloning techniques, since NotI linking clones are directly linked with
      genes.

PMID- 9158963
TI  - The future of gene mapping.

PMID- 9158964
TI  - Citizens' views on health care systems in the 15 member states of the European
      Union.
AB  - This paper provides an initial analysis of a Eurobarometer survey on citizens'
      views on health care systems which was conducted in the 15 European Union Member
      States in 1996. It examines and discusses citizens' satisfaction with the running
      of health care, their views towards major health care reforms and attitudes on
      health care spending.

PMID- 9158965
TI  - Intergenerational equity: an exploration of the 'fair innings' argument.
AB  - Many different equity principles may need to be traded off against efficiency
      when prioritizing health care. This paper explores one of them: the concept of a
      'fair innings'. It reflects the feeling that everyone is entitled to some
      'normal' span of health (usually expressed in life years, e.g. 'three score years
      and ten') and anyone failing to achieve this has been cheated, whilst anyone
      getting more than this is 'living on borrowed time'. Four important
      characteristics of the 'fair innings' notion are worth noting: firstly, it is
      outcome based, not process-based or resource-based; secondly, it is about a
      person's whole life-time experience, not about their state at any particular
      point in time; thirdly, it reflects an aversion to inequality; and fourthly, it
      is quantifiable. Even in common parlance it is usually expressed in numerical
      terms: death at 25 is viewed very differently from death at 85. But age at death
      should be no more than a first approximation, because the quality of a person's
      life is important as well as its length. The analysis suggests that this notion
      of intergenerational equity requires greater discrimination against the elderly
      than would be dictated simply by efficiency objectives.

PMID- 9158966
TI  - Uncompensated hospital care: charitable mission or profitable business decision?
AB  - Provision of hospital uncompensated care is generally assumed to be adversely
      affected as increased healthcare competition decreases demand for compensated
      hospital services. Economic theory, however, suggests the question is more
      complex. Non-profit hospitals are assumed in this paper to maximize utility as a
      function of uncompensated care, subject to the constraint that revenues cover
      costs. For-profit hospitals, in contrast, are assumed to maximize profit while
      recognizing that failure to meet community expectations regarding provision of
      uncompensated care could negatively impact profits. Therefore, for-profit
      hospital supply of uncompensated care focuses on balancing the hospital's
      marginal costs and marginal benefits. These models predict that non-profit
      hospitals will respond to increased competition by reducing the supply of
      uncompensated care. In contrast, for-profit hospitals will increase the supply of
      uncompensated care when market demand decreases since the concurrent decrease in
      compensated care reduces the marginal cost of producing uncompensated care. The
      models also predict that for-profit hospitals will respond to changes in
      community expectations regarding the provision of uncompensated care.

PMID- 9158967
TI  - Using willingness to pay to value close substitutes: carrier screening for cystic
      fibrosis revisited.
AB  - Evidence suggests that previous uses of willingness to pay (WTP) to value close
      substitutes may have failed to discriminate between the alternatives being
      evaluated. This paper reports on the application of a new technique for measuring
      WTP in such contexts. The alternatives evaluated are two methods of screening for
      cystic fibrosis carrier status. The results suggest that the new method is more
      discriminating. Furthermore, the paper provides evidence, from reasons for
      respondents' WTP valuations and regression analyses, that the use of open-ended
      WTP questions is not valid. This is in line with the recommendations of a recent,
      influential, report on the use WTP techniques.

PMID- 9158968
TI  - Economic evaluation of mental health care interventions. A review.
AB  - Due to rising costs, the economic aspects of the mental health care sector are
      receiving increasing attention. This article scrutinizes 91 published studies in
      the field of mental health care, applying methodological criteria drawn from
      epidemiology and economics. The purpose of this study is to provide some insight
      into the quality of economic evaluation in the field of mental health care. The
      article shows that few good full economic evaluations studies have been
      undertaken in the domain of mental health care. One reason for this could be that
      the measurement of effectiveness in mental health care is complicated because of
      the known difficulties with the reliability of psychiatric diagnosis and the lack
      of consensus about the etiology and appropriate treatment for many psychiatric
      illnesses.

PMID- 9158969
TI  - Haggling for a patent: what a government would have to pay for prescription drug
      patents.
AB  - In previous papers (Guell, R. and Fischbaum, M. The Milbank Quarterly 1995; 73: 2
      and Applied Economics letters in press), we established that the allocative
      inefficiency in the prescription drug industry is so pervasive that some remedy
      is warranted. In the first paper, we estimated a lower bound on this inefficiency
      at approximately $3 billion, with an upper bound of approximately $30 billion;
      all on total industry sales of approximately $50 billion. In the second paper, on
      a narrower set of drugs for which sales were $8 billion, we more precisely
      estimated this dead weight loss to be $5 billion. From this we showed that a
      system could exist whereby a government would purchase a drug patent from a
      willing seller, freely distribute it and reap significant efficiency benefits. In
      those papers we considered the possibility that the innovating firm would not
      want to relinquish the patent, but we assumed that they would be indifferent
      between being paid the expected net present value of future monopoly profits and
      reaping those uncertain profits over time. While that may be the case, a more
      likely scenario would be that a negotiation would take place. In the current
      paper I show the bargaining range that would exist under different risk
      preference assumptions and show that this range widens as each side becomes more
      risk averse and narrows if the government threatens to use its power of eminent
      domain. Lastly, I acknowledge the risk of firms "capturing' the government agents
      doing the negotiation. To conclude, I present the circumstances under which the
      proposed agency would likely improve societal welfare and contrast that with the
      circumstances where the presently inefficient system would be made more so by
      government intervention.

PMID- 9158970
TI  - Global budgets and excess demand for hospital care.
AB  - Excess demand is a pervasive feature of health care systems that use global
      budgets to pay for hospital care, regardless of the amount of money spent by
      those systems. This paper presents a theory that explains this feature of global
      budgets. The theory emphasizes that hospital administrators control the
      allocation of their budget, and that they choose quantity and resource intensity
      to maximize their own utility. The equilibrium quantity of care provided may be
      less than quantity demanded by consumers, leading to excess demand for
      admissions. An increase in the hospital's budget may even be associated with an
      increase in excess demand.

PMID- 9158971
TI  - Aboriginal physician use in Canada: location, orientation and identity.
AB  - The main objectives of this paper are to compare Aboriginal and Canadian health
      status and physician use and to identify the factors associated with the use of
      physician services. Data are drawn from the 1991 Aboriginal Peoples Survey (APS)
      and the 1991 General Social Survey (GSS), which are weighted random samples of
      the Aboriginal and total Canadian populations, respectively. The results
      demonstrate that Aboriginals were much less likely to use physician services,
      even though Aboriginals rank their health similarly to the total Canadian
      population. Location becomes an important aspect of both physician use and health
      status, with Aboriginals residing on-reserve generally having lower levels of
      self-assessed health and less likely to have seen a physician. While Aboriginals
      with the poorest health status were more likely to have seen a physician, other
      factors including education were found to be barriers to use of health care.
      Aboriginal identity and cultural orientation provided mixed results.

PMID- 9158972
TI  - Prescribing cost savings by GP fundholders: long-term or short-term?
AB  - Fundholding general practices have been observed to be more successful than non
      fundholders in controlling the growth of their prescribing costs. Debate persists
      over the likely duration of this fundholding effect. Regression analysis of
      changes in prescribing costs for a large sample of practices over 5 years
      supports the view that prescribing cost economies have been short-rather than
      long-term, and that practices entering fundholding did not engage in strategic,
      cost-raising behaviour prior to joining the scheme.

PMID- 9158975
TI  - Evaluation of an educational program to prevent adolescent pregnancy.
AB  - The authors evaluated the effectiveness of a school-based sex education program
      in decreasing rates of sexual intercourse, improving birth control use, and
      decreasing the incidence of pregnancies among teenagers 16 years of age and
      younger. Twenty-one schools received either the McMaster Teen Program or the
      conventional didactic sex education program. Preprogram, the mean age of the
      students was 12.6 years. There were no statistically significant differences
      between groups in time to first sexual activity for males, chi 2(1) = 2.93, p =
      0.09; time to first sexual activity for females, chi 2(1) = 0.50, p = 0.48; and
      time to first pregnancy, chi 2(1) = 1.90, p = 0.17. Significantly more
      experimental group males reported always using birth control at year 1
      (difference 8.9%; 95% confidence interval [CI] = 0.4, 17.4). Limitations of the
      program that may have influenced the results were the exclusion of contraception
      information and its short duration.

PMID- 9158974
TI  - Adolescents' perceptions of health concerns: an exploratory study among rural
      midwestern youth.
AB  - This exploratory investigation examined health concerns of adolescents and their
      perceptions of their peers' health concerns. Data were collected from a
      convenient sample of 419 high school students in rural southern Illinois in May
      1990, using the Adolescent Health Concerns Inventory (AHCI). The AHCI contains
      150 health-related items, grouped into 12 topical subscales. Analysis of the 150
      items found statistically significant differences for all but 2 items: use of
      alcohol and acne. Analysis of the 12 subscales found that students believed other
      teenagers were concerned more about issues related to substance use and abuse,
      human sexuality, and personal health than about the issues they reported as
      concerns for themselves or their best friends. These findings indicate what
      health issues students are personally concerned about. They also suggest that
      students believe their personal health concerns differ from the health concerns
      of their best friends and other teenagers.

PMID- 9158973
TI  - Using sponsorship to promote health messages to children.
AB  - A survey of children aged 8 to 14 years attending a three-day football clinic was
      undertaken to examine the relative impact of different sponsorship strategies
      used to promote health messages. It was found that promotional clothing worn by
      role models was an effective method for promoting a specific health message
      (i.e., "Smoking? No Way!"). Personal endorsement of the health message by an
      external role model and, to a lesser extent, personal endorsement by clinic
      leaders and promotional clothing worn by clinic leaders and external role models
      were also effective in promoting a general health message (i.e., "Don't smoke").
      The implications for health sponsorship and the promotion of commercial products
      to children are discussed.

PMID- 9158976
TI  - Rethinking perceived risk and health behavior: a critical review of HIV
      prevention research.
AB  - Perceived risk of infection, one factor influencing HIV-related behavior
      decisions, has been the focus of expanding research efforts. A body of research
      now exists examining factors related to risk perceptions and the relationship
      between risk perceptions and behavioral decision making. This article examines 60
      quantitative studies of HIV-related risk perceptions, identifies methodological
      and theoretical limitations or gaps in current knowledge, and suggests ways
      future research might better assess the role of risk perceptions and facilitate
      the adoption and maintenance of HIV-related health protective behaviors. The
      authors argue that mixed findings in the quantitative literature are due to (1)
      cross-sectional study designs that constrain or confound the interpretation of
      findings, (2) construct confusion and measurement inconsistencies. (3)
      insufficient consideration of specific subgroup or behavioral differences, and
      (4) inattention to situational norms and other contextual factors that influence
      risk perceptions and behavior.

PMID- 9158977
TI  - The impact of the Wellness Guide/Guia on Hispanic women's well-being-related
      knowledge, efficacy beliefs, and behaviors: the mediating role of acculturation.
AB  - This study examined how acculturation mediated the impact of the California
      Wellness Guide/La Guia del Bienestar on Hispanic women's knowledge, efficacy
      beliefs, and behaviors. Knowledge gaps were found between acculturated and less
      acculturated women. Acculturated mothers had more confidence in their abilities
      to acquire wellness-related information both before and after Guide/Guia
      distribution and also had more assistance-seeking efficacy. Guide/Guia recipients
      were more knowledgeable, had greater confidence in their knowledge and their
      abilities to acquire information, and possessed better information acquisition
      strategies than nonrecipients. The publication also enhanced low-acculturated
      recipients' assistance-seeking self-efficacy. High-acculturated and low
      acculturated recipients of the Guide/Guia were equally likely to have retained
      and used their copies, to anticipate using the publication in the future, and to
      have made a change in behavior as a result of the guide. Finally, the Guide/Guia
      did not increase the knowledge gap between high- and low-acculturated guide
      recipients.

PMID- 9158978
TI  - Reducing inequities through participatory research and community empowerment.
AB  - Information dissemination for behavior change has been the mainstay of
      traditional health education practice, despite lack of demonstrated effectiveness
      in improving the public's health. Following a critique of traditional health
      education practice, an alternative orientation is proposed. Health education for
      social change, based on Paulo Freire's empowerment education and principles of
      participatory research, is examined theoretically within the context of the need
      to address inequities in health. The theoretical justification forms the basis
      for a description of a case study in reducing nutritional inequities. The case
      study analyzes how a process of participatory research and community organization
      was an empowering educational experience for a group of low-income urban women.
      The process of learning and social action is highlighted by chronicling changes
      associated with the experience. The realities and limitations of the project are
      also reflected upon. Implications for health education practice and future social
      change are highlighted.

PMID- 9158979
TI  - Self-efficacy as a predictor of dietary change in a low-socioeconomic-status
      southern adult population.
AB  - There is an increasing emphasis on designing health promotion interventions for
      low-socioeconomic-status (SES) individuals. However, many previously developed
      behavior change tools have not been tested in this population. Self-efficacy was
      measured at pre- and postintervention as part of a randomized clinical trial to
      reduce cholesterol levels in rural low-SES Southern adults. A 22-item scale was
      designed and validated to measure subjects' confidence in their abilities to make
      dietary changes. High mean self-efficacy was noted in both control and
      intervention subjects at pre- and postintervention. Mean self-efficacy score was
      a significant predictor of dietary change at both preintervention and
      postintervention. This study demonstrates that self-efficacy is a predictor of
      ability to make dietary changes in a low-SES rural population. This finding is of
      significance to researchers and practitioners wishing to design theory-based
      health promotion interventions in this population.

PMID- 9158980
TI  - Photovoice: concept, methodology, and use for participatory needs assessment.
AB  - Photovoice is a process by which people can identify, represent, and enhance
      their community through a specific photographic technique. As a practice based in
      the production of knowledge, photovoice has three main goals: (1) to enable
      people to record and reflect their community's strengths and concerns, (2) to
      promote critical dialogue and knowledge about important issues through large and
      small group discussion of photographs, and (3) to reach policymakers. Applying
      photovoice to public health promotion, the authors describe the methodology and
      analyze its value for participatory needs assessment. They discuss the
      development of the photovoice concept, advantages and disadvantages, key
      elements, participatory analysis, materials and resources, and implications for
      practice.

PMID- 9158981
TI  - Remembering early roots.

PMID- 9158982
TI  - Predicting air-balloon and water-filled infant catheter frequency responses.

PMID- 9158983
TI  - Imaging neural activity using MEG and EEG.

PMID- 9158984
TI  - Zona pellucida microdrilling with a 1.48 microns diode laser.

PMID- 9158985
TI  - Improving oral medication compliance with an electronic aid.

PMID- 9158986
TI  - IUGR detection by ultrasonographic examinations using neural networks.

PMID- 9158987
TI  - Ultrasonic Doppler measurement using a pseudo-continuous mode.

PMID- 9158988
TI  - Assessing liver tissue fibrosis with an automatic computer morphometry system.

PMID- 9158990
TI  - The Z-transform of the compound action potential. A method for deriving nerve
      fiber density distribution.

PMID- 9158989
TI  - Analysis of physiological time series using wavelet transforms.

PMID- 9158991
TI  - HMOs and medical technology.

PMID- 9158992
TI  - Biological and health effects of electric and magnetic fields from video display
      terminals. A technical information statement.

PMID- 9158993
TI  - Extracting the teeth from the False Claims Act.

PMID- 9158994
TI  - Old World cutaneous leishmaniasis.

PMID- 9158995
TI  - Dermatology and the recently returned traveler: infectious diseases with
      dermatologic manifestations.

PMID- 9158996
TI  - 5 alpha-reductase inhibitors--a new hope in dermatology?

PMID- 9158997
TI  - The proportion of medical consultations motivated by skin diseases in the health
      centers of Bamako (Republic of Mali).
AB  - BACKGROUND: Skin diseases have recently been identified as a public health
      problem in developing countries. However, most studies on skin diseases in
      developing countries, have been conducted in specialized dermatologic centers.
      Data on the proportion of consultations motivated by skin diseases in
      nonspecialized health centers in developing countries are scarce. In order to
      appreciate the request for dermatologic care of the population of a developing
      African country, we attempted to measure this proportion in health centers of
      Bamako, the capital of Mali. METHODS: Eight out-patient health centers were
      randomly selected in Bamako, and the medical registers for the first 6 months of
      1993 were consulted. RESULTS: Out of a total of 14,058 consultations given, 1639
      (11.7%) were motivated by skin diseases. The main diagnoses registered were
      pyoderma (42.2% of all the dermatologic diagnoses), eczema (15.5%), scabies
      (8.5%), and fungal infections (7.9%). CONCLUSIONS: The high proportion of
      ambulatory consultations in health centers in Bamako motivated by skin diseases
      suggests that they are an important health problem for the population of this
      city. Public health policies should be implemented in order to manage this
      problem.

PMID- 9158998
TI  - The association of chronic urticaria and angioedema with autoimmune thyroiditis.
AB  - BACKGROUND: An increased frequency of autoimmune thyroiditis is seen in patients
      with chronic urticaria and angioedema (CUA) and it has been hypothesized that
      autoimmunity may be playing a role in the pathogenesis of CUA. The aim of this
      study was to learn the extent of autoimmune thyroid disease in a series of
      patients who presented with CUA. METHODS: Thyroid function tests and thyroid
      autoantibodies were measured by radioimmunoassay and immunoradiometric assay
      respectively in 94 CUA patients and 80 age- and sex-matched healthy volunteers.
      RESULTS: Eleven patients (11.7%) were found to have thyroglobulin antibodies
      (TGA) and nine patients (9.57%) thyroid microsomal (TMA) titers ranging from 150
      to 1340.37 and from 165.73 to 8000 IU/mL respectively. Both antibodies were
      detected in three control cases (3.7%). The association was statistically
      significant (P < 0.01). Six of 11 patients had thyroid dysfunction and the other
      five cases were euthyroid. CONCLUSIONS: Our results justified the use of TMA and
      TGA for the early diagnosis of autoimmune thyroiditis in combination with CUA.
      The higher frequency of these antibodies in our patients, along with results from
      previously published data, suggest that this entity may reflect an autoimmune
      basis in some CUA patients. Thyroid function tests are not enough to rule out
      thyroid disease, and thyroid antibody tests should be carried out in all patients
      with CUA.

PMID- 9158999
TI  - Linear IgA bullous dermatosis in south India.
AB  - BACKGROUND: A study of five cases of linear IgA dermatosis (LABD) in a referral
      hospital in South India is presented. METHODS: A dermatologic examination, skin
      biopsy, and direct immunofluorescence were carried out on all patients. Patients
      were then followed up. RESULTS: All five cases showed linear IgA deposits at the
      dermo-epidermal junction. One case in addition showed IgG and C3 deposits. All
      cases responded to treatment with dapsone. The treatment duration varied from 14
      to 16 months and the fifth patient is still on treatment after 37 months.
      CONCLUSIONS: Linear IgA bullous dermatosis is a self-limiting bullous disorder.
      To the best of our knowledge this is the first report of LABD from India.

PMID- 9159000
TI  - Postpemphigus acanthomata: a sign of clinical activity?
AB  - BACKGROUND: Pemphigus is a group of vesiculobullous disorders in which the
      blisters usually heal with hyper or hypopigmentation. The appearance of
      acanthomata at sites of previous blisters has been noted in some cases. METHODS:
      All cases of pemphigus admitted to the Madras Medical College hospitals during a
      2-year period from March 1993 to March 1995 were taken into the study and
      screened for the presence of acanthomata. RESULTS: Fifty-two cases of pemphigus
      were identified, 47 of pemphigus vulgaris and five of pemphigus foliaceus; and of
      these 13 developed acanthomata when the blisters healed. Ten of these cases were
      of pemphigus vulgaris and three were of pemphigus foliaceus; biopsy of these
      lesions showed hyperkeratosis, acanthosis, papillomatosis, and intraepidermal
      clefting. Immunofluorescence carried out in two of these acanthomata also showed
      intercellular fluorescence. CONCLUSIONS: The occurrence of acanthomata in healed
      lesions of pemphigus is not uncommon; because histopathologic and
      immunofluorescence evidence of disease activity is present, cases of this sort
      require careful follow-up.

PMID- 9159001
TI  - Embolia cutis medicamentosa.
AB  - A 35-year-old man presented with a painful skin necrosis after a deep
      ventrogluteal injection of diclofenac and dexamethasone for treatment of severe
      back pain. Immediately after the injection, the patient felt a strong pain just
      above the injection site. In the following days a remarkable necrosis developed
      in the upper gluteal region. Topical therapy with antiseptics and a topical
      corticosteroid cream plus analgesia with tramadole revealed no improvement of the
      symptoms. We excised the necrotic area. Within 1 day, the patient was without
      pain.

PMID- 9159002
TI  - Generalized epidermolytic hyperkeratosis in a child born to a parent with
      systematized epidermolytic linear epidermal nevus.

PMID- 9159003
TI  - Acantholytic dermatosis in chronic renal failure.

PMID- 9159004
TI  - Lymphomatoid papulosis and FK 506.

PMID- 9159005
TI  - Pyoderma gangrenosum associated with anticardiolipin antibodies in a pregnant
      patient.

PMID- 9159006
TI  - Papular umbilicated granuloma annulare in association with Alagille syndrome.

PMID- 9159007
TI  - Idiopathic unilateral circumscribed hyperhidrosis.

PMID- 9159008
TI  - Chronic leg ulcers associated with hereditary protein S deficiency.

PMID- 9159009
TI  - Colchicine as a novel therapeutic agent in chronic bullous dermatosis of
      childhood.
AB  - BACKGROUND: The treatment of chronic bullous dermatosis of childhood (CBDC) so
      far has been limited to the use of corticosteroids and the sulfa group of drugs,
      e.g. daspsone and sulfapyridine. Furthermore, the therapy of CBDC cases with
      associated G6 PD deficiency is restricted only to systemic steroids.
      Histopathologically CBDC is characterized by the presence of predominantly
      neutrophilic infiltration and because it has been proven to exert strong anti
      inflammatory effects through the inhibition of neutrophils, colchicine was
      mandated for its use in CBDC. METHODS: To avoid the detrimental side-effects of
      the long-term use of steroids in children, an alternative anti-inflammatory drug
      like colchicine was considered. Patients with G6 PD deficiency and those who were
      not satisfactorily controlled with steroid therapy, and who in addition developed
      unacceptable side-effects like cushingoid faces and hypertrichiosis, were treated
      with the drug. RESULTS: Eight patients were given colchicine, five (62.5%) of
      which showed complete remission within 4-6 weeks of starting the therapy. The
      remaining three (37.5%) also responded but required adjuvant small doses of
      steroids to maintain the remissions. The drug was very well tolerated and no side
      effects were observed. CONCLUSIONS: Colchicine is, therefore; found to be an
      effective treatment in CBDC and has enhanced our armamentarium of therapeutics
      for this condition, especially in children with G6 PD deficiency.

PMID- 9159010
TI  - Khite: a non-Western technique for temporary hair removal.
AB  - BACKGROUND: Khite (also known as fatlah in Egypt) is a manual technique of
      temporary vellus hair removal that is widely performed in the Middle East.
      METHODS: The technique of khite is reviewed as illustrated. RESULTS: Khite is an
      effective method of removing unwanted vellus hairs. CONCLUSIONS: Dermatologists
      in all parts of the world should be familiar with khite, because the ease of
      international travel may bring patients to their attention who have khite
      association complications such as erythema, folliculitis, and secondary
      pigmentary changes.

PMID- 9159011
TI  - Plasmapheresis in toxic epidermal necrolysis.
AB  - BACKGROUND: The treatment of toxic epidermal necrolysis (TEN) is usually based on
      the removal of the offending drug(s), fluid replacement, nutritional support, and
      local management. The mortality and morbidity, however, remain high and the death
      rate may be reduced to 10% only in special centers that use biologic dressings.
      Plasma exchange (PE) was proven efficacious in small series of patients and of no
      particular value in others. METHODS: Seven patients suffering from severe TEN
      covering 30%-80% of body surface area and having two or four mucous membranes
      involved, were included in this open study. Malignancy (Hodgkin's disease, brain
      tumor) and a variety of medicaments (carbamazepine, allopurinol,
      diphenylhydantoin, cefaclor, amoxicyllin with clavullanic acid) were considered
      as causally implicated. One to four PEs of 2.5 L were given on alternate days in
      six patients and on a daily basis in the seventh. RESULTS: All patients recovered
      successfully from their disease. No new lesions appeared after the first PE in
      four patients. Neither adverse reactions from this therapy nor sequelae from TEN
      were observed after a long follow-up lasting up to 8 years. CONCLUSIONS: Although
      PE is expensive and requires easy venous access to be performed, it could be
      listed in the first line of TEN therapy. The method is safe and efficacious,
      providing prompt relief from pain and rapid cessation of necrolysis. The
      alternate day PEs are considered preferable to the everyday regimen.

PMID- 9159012
TI  - History of prolonged occlusive therapy for psoriasis.

PMID- 9159013
TI  - Second International Symposium on Onychomycosis, Florence, Italy, September 28
      29, 1995.

PMID- 9159014
TI  - Peripheral neuropathy in scleroderma successfully treated with amitriptyline.

PMID- 9159015
TI  - Hypertrichosis cubiti: a case in a Sri Lankan family.

PMID- 9159016
TI  - Polysensitivity and familiar occurrence in fixed drug eruption.

PMID- 9159017
TI  - Longitudinal pigmented nail bands during hydroxyurea therapy.

PMID- 9159018
TI  - Dermatologic disorders associated with viral hepatitis.

PMID- 9159019
TI  - Experimental psoriasis models.

PMID- 9159020
TI  - Green hair discoloration due to selenium sulfide.

PMID- 9159021
TI  - Azithromycin for the treatment of acne.

PMID- 9159022
TI  - Kinetics of HIV-1 RNA concentration changes in pediatric patients.
AB  - Recent studies have used potent antiviral agents to investigate the kinetics of
      HIV infection in vivo. They provided estimates for important kinetic parameters,
      including the decay constants for circulating virus and infected CD4+cells.
      However, since all of these studies fundamentally rely on the use of antiviral
      agents, it would be useful to develop other approaches capable of independently
      verifying the values of the kinetic parameters through other means. Since CD4+
      cells are known to exhibit diurnal variations and since there have been
      suggestions that circulating virus concentrations also vary in a diurnal fashion,
      as well as nonperiodically, we developed a mathematical model to describe those
      natural variations. The model predicted variations in viral RNA concentrations
      and produced estimates of the values of viral kinetic parameters without the use
      of antiviral agents. To compare the model with experimental data we measured the
      temporal dependence of the concentration of plasma viral RNA obtained from
      pediatric HIV-1 patients. The data analysis led to finding diurnal variation in
      the viral RNA and an estimate of the circulating virus half-life in the order of
      few hours, in reasonable agreement with the estimates obtained using antiviral
      agents. These results are the first demonstration of diurnal variations in AIDS
      patients and confirm the order of magnitude of the virus half-life found by using
      antiviral drugs. These findings may have implications for understanding HIV-1
      pathogenesis and the development of therapeutic protocols.

PMID- 9159023
TI  - Neuronal damage and its relation to dementia in acquired immunodeficiency
      syndrome (AIDS).
AB  - There are an estimated 21.8 million people infected with human immunodeficiency
      virus (HIV) worldwide [Weekly Epidemiol Rec 1996; 27:204-208] and 90% of these
      people will have some form of neuropathological abnormality during the course of
      acquired immunodeficiency syndrome (AIDS). In this review, we will highlight the
      primary HIV-associated brain disorders. The role of HIV proteins and cytokines on
      neuronal damage will be assessed. We will also discuss the role of neuronal loss
      and functional damage in HIV-associated dementia.

PMID- 9159024
TI  - Airway hyperreactivity is associated with specific leukocyte subset infiltration
      in a mouse model of allergic airway inflammation.
AB  - Airway hyperreactivity is defined as an increased bronchoconstrictor response to
      physical, pharmacological, or other stimuli. Patients with asthma develop airway
      hyperreactivity as well as peribronchial inflammation. We employed an established
      schistosome soluble egg antigen (SEA)-induced murine model of allergic
      inflammation to examine the temporal relationship between airway hyperreactivity
      and leukocyte subset infiltration. Dose response curves of intravenous
      methacholine were used in mice to characterize airway reactivity at various time
      points after intranasal SEA rechallenge. Cellular infiltration into the airspace
      was assessed by bronchoalveolar lavage. Airway hyperreactivity increased as early
      as 1 h postchallenge. Peak hyperreactivity occurred at 8 h postchallenge.
      Subsequently, reactivity decreased at 24 h and fell to the level observed in
      controls by 48 h. Neutrophil influx correlated directly with the increase in
      airway reactivity, as neutrophils were observed as early as 1 h, peaked at 8 h,
      diminished by 24 h and were not detected at 48 h post-SEA challenge. In contrast,
      eosinophil infiltration was not observed until 24 h and peaked at 48 h post-SEA
      rechallenge when increases in airway reactivity were not detected. Airway
      resistance induced by methacholine correlated with neutrophil (r2 = 0.90) but not
      eosinophil (r2 = 0.1) infiltration. These results suggest that the airway
      hyperreactivity observed during allergic airway inflammation correlates with
      airways neutrophilia and weakly eosinophil accumulation.

PMID- 9159025
TI  - Localization of thyrotropin-releasing hormone mRNA expression in the rat heart by
      in situ hybridization histochemistry.
AB  - Our laboratory has recently detected mRNA of thyrotropin-releasing hormone (TRH)
      in the rat heart. The density of mRNA for TRH is five-fold higher in the atria
      than in the left and right ventricle. We also found TRH receptor mRNA and 3H-TRH
      binding sites in both ventricles. Cardiac contractility was stimulated after
      intracoronary administration of TRH. This study was performed to investigate the
      localization of TRH in the heart. We utilized in situ hybridization
      histochemistry (ISHH) to localize TRH mRNA expression in the rat heart. ISHH was
      performed on fresh frozen heart tissue sections which were hybridized with a
      specific 35S-TRH oligo probe and subsequently processed by autoradiography. The
      autoradiographic signals corresponding to TRH mRNA were analyzed with an image
      program. For positive controls TRH mRNA was identified in the hypothalamic
      paraventricular nucleus. This test confirms the specificity of the TRH oligo
      probe. Cardiac hybridization signals were observed predominantly in the atria and
      localized preferentially in atrial connective tissues, vascular adventitia and
      atrial cardiomyocytes. No hybridization signals were found in ventricular
      cardiomyocytes. These observations suggest that TRH is synthesized in atrial
      myocytes and atrial vascular structures. Based on studies which show synthesis of
      the TRH receptors in ventricular cardiomyocytes, we hypothesize that atrial TRH
      is an endocrine source for the stimulation of ventricular contractility and that
      endothelial and adventitial TRH may play a role(s) in the regulation of the
      growth and/or vasomotor tome of the cardiac vascular system.

PMID- 9159026
TI  - PECAM-1 expression in human mesothelial cells: an in vitro study.
AB  - Mesothelial cells are actively involved in inflammatory processes by expressing a
      set of cell adhesion molecules (CAMs). Transmigration of leukocytes into inflamed
      tissues requires a chemotactic stimulus and engagement of platelet-endothelial
      cell adhesion molecule-1 (PECAM-1). To investigate the kinetics involved in
      peritonitis, pure cultures of mesothelial cells are necessary. In previous
      studies, we have found that human mesothelial cells (HOMES) show a weak
      constitutive expression of PECAM-1, which cannot be further stimulated by
      cytokines. It is known that all serous cavities and body fluids contain numerous
      macrophages which strongly express this adhesion molecule. To identify the cells
      responsible for the expression of PECAM-1, mesothelial cells freshly obtained
      from omental tissue were isolated using PECAM-1-conjugated magnetic beads by cell
      sorting. For these studies, the negative as well as the positive fraction of
      isolated cells were used. As a control, freshly isolated monocytes were studied.
      Cell cultures were characterized by light and electron microscopy, as well as
      immunocytochemistry. The negative cell fraction was cultivated and stimulated for
      different times with tumor necrosis factor-alpha (30 and 300 U/ml), interleukin-1
      beta (10 and 100 U/ml) and interferon-gamma (500 U/ml) and PECAM-1 expression was
      analyzed by a comparative quantitative cell enzyme immunoassay (EIA). The
      positive cell fraction was treated in the same manner. Both fractions of isolated
      cells showed strong positivity for cytokeratins 8, 18, 7 and 19, as well as
      vimentin. CD68, a monocyte marker, was not detected on mesothelial cells. In
      addition, EIA analysis confirmed the constitutive expression of PECAM-1 obtained
      from previous studies. This expression on HOMES was not inducible, irrespective
      of the type and concentration of cytokine studied. These data confirm PECAM-1
      expression on mesothelial cells obtained from human omental tissue and suggest a
      critical role in transmigration of leukocytes during peritoneal inflammation.

PMID- 9159027
TI  - Diet-induced hypercholesterolemia increases endothelin-1 release by aortic
      endothelial cells.
AB  - Our previous studies demonstrated the morphological heterogeneity of endothelial
      cells (ECs) and the emergence of large multinucleated ECs in human and animal
      atherosclerotic lesions. To investigate the functional alteration of ECs in diet
      induced atherosclerosis, immunoreactive endothelin-1 (irET-1) release by ECs of
      the rabbit aorta was correlated with scanning electron microscopy. Rabbits were
      fed a cholesterol diet for 12 weeks: by scanning electron microscopy, the area of
      ECs in the aorta increased in the hypercholesterolemic (HC) group as
      atherosclerosis progressed. Cultured ECs of the HC group released significantly
      more irET-1 than ECs of the control. The plasma irET-1 level was also elevated in
      the HC group. The results obtained suggest that accelerated secretion of ET-1 by
      ECs contributes to the development of atherosclerotic vascular lesions.

PMID- 9159028
TI  - Involucrin and tumor progression in the uterine cervix.
AB  - The expression of involucrin, a cytoplasmic protein synthesized during squamous
      maturation, was assessed by immunocytochemistry in different grades of cervical
      lesions. In normal/benign cervical epithelium and low-grade squamous
      intraepithelial lesions [SILS or cervical intraepithelial neoplasia (CIN)-1]
      involucrin showed intense and homogenous cytoplasmic expression in the spinal
      layers of 75 and 57% of samples, respectively. The basal cell layers showed no
      expression of involucrin. In high-grade SILs (CIN-2/3) 40% of the samples showed
      diffuse and focal cytoplasmic expression of involucrin in the differentiated
      basaloid cells. In the squamous cell carcinomas (SCCs) analyzed, well
      differentiated tumors showed intense focal expression in 61% of the cases,
      moderately differentiated SCCs showed intense expression in 33% of the cases,
      while poorly differentiated SCCs (PDSCC) showed only a mild focal expression in
      7% of cases. With increasing severity of the lesions, patchy expression of
      involucrin with a mixture of reactive and nonreactive cells predominated.
      Patterns of immunocytochemical staining for involucrin in cervical lesions of
      different grades, from low-grade to high-grade SILs, and invasive carcinoma may
      be of critical importance, if loss of involucrin expression is used as a
      criterion for neoplastic transformation in cervical epithelium. Our findings
      suggest that involucrin may be a sensitive marker in identifying the
      differentiation status of the lesion while the absence of involucrin in PDSCC may
      be helpful in differential diagnosis.

PMID- 9159029
TI  - Selective modulation of cell adhesion molecules on lymphocytes by bromelain
      protease 5.
AB  - Human peripheral blood mononuclear cells from healthy donors were treated ex vivo
      with the proteolytic enzyme bromelain and studied by flow cytometry. Bromelain
      treated lymphocytes exhibited 60-90% reduced cell surface staining for CD44 and
      CD62-L molecules. While the staining for molecules CD16, CD56 and CD49d was
      unaffected, a moderate increase (10-40%) in expression of the beta(2)-integrins
      CD11a-c was seen. This selective modulation of cell adhesion molecules (CAM) was
      seen on T cells and NK cells, as well. The selective modulation of CAM may help
      explain some of the clinical effects observed after bromelain treatment in
      patients suffering from chronic inflammatory disease, HIV and cancer.

PMID- 9159030
TI  - Preoperative evaluation of the curative resectability of gastric cancer by
      abdominal computed tomography and ultrasonography: a prospective comparison
      study.
AB  - OBJECTIVES: We compared the ability of preoperative abdominal computed tomography
      (CT) with that of preoperative abdominal ultrasonography (US) in predicting the
      extent of tumor growth and the curative resectability of gastric cancer. METHODS:
      Abdominal CT and US were done in 95 patients with gastric adeno-carcinoma. The
      radiologic findings were prospectively compared with surgical and pathologic
      findings. RESULTS: The sensitivities of abdominal CT and US in detecting the
      perigastric lymph node involvement were 26.6% and 20%, respectively. The
      sensitivity of abdominal CT in predicting the pancreatic invasion (60%) was
      better than that of abdominal US (20%). However, there were 6 false positive
      diagnosis of pancreatic invasion by abdominal CT; in contrast, there was no false
      positive diagnosis of pancreatic invasion by abdominal US. Of 95 patients who
      underwent surgical exploration, 14 were found to have unresectable tumors because
      of extragastric organ involvement and distant metastases. Abdominal CT falsely
      predicted 8 of 14 cases in which curative gastric resection was impossible as
      resectable. Moreover, abdominal CT falsely predicted 5 of 81 cases in which
      curative gastric resection was possible as unresectable. Abdominal US falsely
      predicted 12 of 14 cases in which curative surgery was impossible as resectable.
      CONCLUSION: Preoperative abdominal Ct and US did not accurately predict the tumor
      extent and the curative resectability of the gastric cancer. Especially,
      abdominal CT finding of pancreatic invasion by gastric cancer should not be a
      contraindication for surgical exploration.

PMID- 9159031
TI  - Differences in immunophenotyping of mucosal lymphocytes between ulcerative
      colitis and Crohn's disease.
AB  - OBJECTIVES: Immunologic studies have characterized the numbers and types of
      inflammatory cells in diseased inflammatory bowel disease (IBD) mucosa but have
      yielded conflicting results regarding intestinal lymphocytes activation in IBD.
      We investigated the levels of lymphocytes subsets, interleukin-2 receptor,
      transferrin receptor, and T cell receptors in mainly isolated lamina propria
      lymphocytes. Including intraepithelial lymphocytes of normal colonic mucosa or
      IBD (ulcerative colitis and Crohn's disease) mucosa to understand the
      pathogenesis of IBD. We have results from this study. RESULTS: 1) In comparing
      ulcerative colitis with control, IL-2R (p < 0.05), TR (p < 0.01), and CD3/HLA-DR
      (< 0.05) showed a significant increase. 2) In comparing Crohn's disease with
      control, CD3 (P < 0.05), TCR alpha/beta (p < 0.01) and TCR gamma/delta (p < 0.05)
      showed a significant decrease. 3) In comparing Crohn's disease with ulcerative
      colitis, CD19 (p < 0.01), TR (p < 0.01), TCR alpha/beta (p < 0.01) and TCR
      gamma/delta (p < 0.05) showed a significant decrease. CONCLUSION: From these
      results, there are increased T cell markers, IL-2R, TR, and CD3/HLA-DR in UC, but
      differently, decreased CD3, TCR alpha/beta and TCR gamma/delta in CD compared
      with control. In addition, definitive differences in lymphocytes markers, CD19,
      TR, TCR alpha/beta and TCR gamma/delta, which are higher in UC than in CD, may
      elucidate the different immunopathogenesis between UC and CD.

PMID- 9159032
TI  - Gallbladder motility change in late pregnancy and after delivery.
AB  - OBJECTIVES: The incidence of gallstone disease has increased recently in Korea
      and there seems to be an increased prevalence of gallstones when in association
      with pregnancy. Although the pathogenesis is incompletely defined, and altered
      motility of the gallbladder may contribute to the increased risk of gallstones
      during pregnancy. METHODS: We measured gallbladder volume using real-time
      ultrasonography to find out the mechanism for the changes of gallbladder motility
      during late pregnancy. Eighteen pregnant women took the gallbladder
      ultrasonography during their last trimester of pregnancy and after delivery;
      gallbladder volume and ejection fraction were calculated in each patient.
      RESULTS: Fasting gallbladder volumes increased significantly in the last
      trimester of pregnancy (25.28 +/- 14.26ml) compared with postpartum (17.44 +/-
      5.82 ml) (p < 0.05). Gallbladder volumes measured after fatty meals showed more
      increment in pregnant women (10.13 +/- 7.19 ml) than in those after delivery
      (4.34 +/- 3.36 ml) (p < 0.005). A significantly reduced gallbladder ejection
      fraction was found in the pregnant group (60.56 +/- 18.80%) compared with those
      after delivery (77.48 +/- 13.37%) (p < 0.005). CONCLUSION: Gallbladder motility
      in late pregnancy shows significant impairment compared with that in postpartum.
      Thus, we suggest that gallbladder hypomotility may occur during late pregnancy,
      and this impairment of gallbladder motility may play an important role in
      gallstone formation.

PMID- 9159033
TI  - Hepatitis C virus genotypes in Korea and their relationship to clinical outcome
      in type C chronic liver diseases.
AB  - OBJECTIVES: The relationship between HCV genotype and the development of more
      serious liver disease has not been clearly established. This study was to
      investigate the distribution pattern of HCV genotypes in Korea and their
      relationship to the viremic level and to progression of chronic liver disease.
      METHODS: Study population was 217 patients with type C chronic liver disease.
      They were divided into 4 groups; 83 patients with near-normal ALT (group 1), 64
      patients with elevated ALT (group 2), 20 patients with decompensated liver
      cirrhosis (group 3) and 50 patients with hepatocellular carcinoma (group 4). HCV
      genotypes were determined by reverse transcription polymerase chain reaction (RT
      PCR) using mixed primer sets, and then the fidelity of genotyping was confirmed
      by cloning and sequencing. HCV RNA concentration was measured by quantitative
      competitive RT-PCR for 23 patients in group 2. RESULTS: The genotypes could be
      determined in 166 (76%) out of 217 patients. Type 1b and type 2a were
      predominantly occurring over the other types in somewhat similar frequency (45%
      and 51%, respectively). The genotype distribution of type 1b and 2a among four
      different groups showed 42% and 54% in group 1, 49% and 45% in group 2, 53% and
      47% in group 3 and 41% and 57% in group 4; thus there was no significant
      difference in genotype distribution among 4 different disease groups. However,
      the viremia levels in patients with genotype 1b infection were significantly
      higher than those with genotype 2a. CONCLUSION: Genotype 2a infection is as
      prevalent as genotype 1b in Korea, and genotype 2a infection may pose no less
      risk for progression of disease despite lower replication level than genotype lb
      infection.

PMID- 9159034
TI  - Viral loads and E2/NS1 region sequences of hepatitis C virus in hepatocellular
      carcinoma and surrounding liver.
AB  - OBJECTIVES: Numerous epidemiologic data have documented that chronic infection by
      hepatitis C virus (HCV) is a major risk factor for the development of
      hepatocellular carcinoma (HCC). But the molecular mechanism underlying these
      strong epidemiologic associations between HCV and HCC has not be elucidated. We
      observed the changes of HCV in HCC to investigate the association of HCV with
      HCC. METHODS: We used competitive and quantitative polymerase chain reaction and
      dideoxy-nucleotide chain termination method to compare HCV titers and sequences
      of the hypervariable region of E2/NS1 region of four isolates from the HCC and
      surrounding cirrhotic liver tissues in tow anti-HCV positive patients. RESULTS:
      The copy numbers of HCV-RNA were 1 x 10(6) and 4 x 10(6)/gm wet weight of HCC,
      and 8 x 10(7) and 3.2 x 10(8)/gm wet weight of cirrhotic liver tissues from
      patient-1 and -2. The sequence differences between HCV RNA in HCC and in
      cirrhotic liver were two and five nucleotides in patient-1 and in patient-2
      respectively. The amino acid sequences were changed in one and two site in each
      patient. CONCLUSION: These findings may suggest the possible etiological role of
      HCV in carcinogenesis of HCC, but complete sequence analysis of HCV including
      multiple isolates in the same patient, should be performed in many cases.

PMID- 9159035
TI  - Atrial fibrillation in patients with permanent VVI pacemakers: risk factors for
      atrial fibrillation.
AB  - OBJECTIVES: Atrial fibrillation (AF) does not only deteriorate the cardiac
      function and increases the thromboembolic risk but also triggers rapid and
      irregular ventricular rhythm in patients with atrial synchronous pacing. However,
      the risk factors for the development of AF in patients with pacemakers are not
      clearly determined yet. The present study was designed to determine the risk
      factors for AF in patients with VVI pacemakers. METHODS: This study included 80
      patients (41 sick sinus syndrome, 39 AV block) who were followed for more than 6
      months or developed AF regardless of the duration of follow-up after implantation
      of VVI pacemakers. Patients were divided into two groups according to whether or
      not AF developed during follow-up (mean: 25.7 +/- 2.5 months): group A developed
      AF and group B did not. The underlying arrhythmias, cardiovascular risk factors,
      left atrial size, characteristics of P wave were compared between the two groups.
      RESULTS: The mean age of the patients was 58.9 +/- 11.4 years and 28 (35%) were
      male. AF developed in 13 (16.3%) of 80 patients with VVI pacemakers. Sick sinus
      syndrome (SSS) as an underlying arrhythmia was significantly more frequent in
      group A than group B (84.6% vs. 44.8%, p < 0.01). P wave width was greater in
      group A (127.6 +/- 24.8 ms) than in group B (110.7 +/- 17 ms) (p < 0.05). There
      was, however, no significant difference in cardiovascular risk factors, left
      atrial size, P wave axis and amplitude between the two groups. CONCLUSION: These
      results suggest that sinus node dysfunction and intra-atrial conduction delay may
      be the risk factors for AF in patients with VVI pacemakers. Further studies are
      needed to determine how sick sinus syndrome and intra-atrial conduction delay
      increase the risk for AF in patients with VVI pacemakers.

PMID- 9159036
TI  - Does arterial hypotension due to cardiogenic shock in older patients lead to
      functional oliguria or to acute renal failure?
AB  - OBJECTIVES: Reports indicate some differences in the outcome of prolonged
      arterial hypotension due to cardiogenic shock: acute renal failure in older and
      more often functional oliguria in younger patients. The aim of the study is to
      analyze prolonged hypotension due to acute myocardial infarction in older and
      younger patients and to answer the question: does prolonged hypotension, due to
      acute myocardial infarction, lead to acute renal failure or to functional
      oliguria in older patients. METHODS: During a 10-year observation, a study of 11
      older (> 65 years) and 7 younger patients (< 65 years), suffering from acute
      myocardial infarction and cardiogenic shock, is presented: clinical data and
      laboratory: diuresis, sodium in urine, creatinine urine/plasma ratio, urine
      osmolality, osmolality urine/plasma ratio, renal failure index and fractional
      excretion of filtered sodium. RESULTS: In 7 older and 5 younger patients,
      natriuresis indicated acute renal failure. The ratio of creatinine in urine and
      plasma in 3 older and 5 younger indicated functional oliguria; in 3 older and 1
      younger, acute renal failure; and in 5 older and 1 younger, borderline values. In
      7 older and 2 younger, the values of urine osmolality were in the range of
      functional oliguria and, in 4 older and 5 younger, borderline values between
      those two parameters, as the osmolality quotient in urine and plasma. The values
      of the renal failure index in all older and younger patients was lower than 3.0
      (in 6 older and 3 younger, lower than 1.0) indicated functional oliguria, as the
      fractional excretion of filtered sodium Of 9 older patients who died, 5 were
      examined by autopsy, and 3 out of 4 younger who died. All had myocardial fibrosis
      and scars, apart from recent myocardial infarction and coronary atherosclerosis.
      In 2 older, acute tubular necrosis was found while in 2 no renal changes were
      found. In 2 younger, no renal changes were found and in 1 showed disseminated
      intravascular coagulation. CONCLUSION: Acute renal failure due to cardiogenic
      shock in older patients is functional, or is rare renal.

PMID- 9159037
TI  - The factors related to recurrence after transcatheter arterial embolization for
      the treatment of hemoptysis.
AB  - OBJECTIVES: Massive hemoptysis is a major clinical problem associated with high
      morbidity and mortality. Transcatheter arterial embolization is widely used for
      the treatment of massive hemoptysis, but it was reported that the recurrence rate
      after embolization is 12-54% in the previous studies. We evaluated the
      therapeutic effect of transcatheter arterial embolization for the treatment of
      massive hemoptysis and the factors related to recurrence. METHODS: We reviewed 51
      patients (M:F = 36:15) of transcatheter arterial embolization for the treatment
      of massive hemoptysis from Jan 1988 to Dec 1994, retrospectively. RESULTS: After
      arterial embolization, immediate successful control (< 1 wk) of massive
      hempotysis was achieved in 48 of 51 patients (94.1%) and recurrence of hemoptysis
      was observed in 17 of 51 patients (33.3%) during the follow-up period. The
      patients with non-bronchial artery hemoptysis and multiple artery bleeding had
      increased tendency of recurrence (77.7%). On the previous history of hemoptysis,
      the patients with massive hemoptysis (> 400 ml/24hr) or frequent history of
      hemoptysis had increased tendency of recurrence (87.5%, 72.7%). CONCLUSION:
      Transcatheter arterial embolization is a useful and safe procedure for immediate
      control in massive hemoptysis. However, the patients with this procedure had a
      potentiality for recurrence. We suggest that close follow-up and caution will be
      needed in the patients with multiple artery bleeding or with large amounts of
      hemoptysis or with previous episodes more than 3 times.

PMID- 9159038
TI  - Serum and urine soluble HLA class I antigen concentrations are increased in
      patients with hemorrhagic fever with renal syndrome.
AB  - OBJECTIVES: In order to evaluate the association between the Hantaan virus
      induced cellular-immune response and clinical severity in patients with
      hemorrhagic fever with renal syndrome (HFRS). METHODS: We serially measured the
      serum (n = 16) and urine (n = 6) concentrations of soluble HLA class 1 antigen
      (sHLA-l) and clinical powameters in patients with HFRS. RESULTS: Serum sHLA-I
      concentrations in patients with HFRS were significantly higher than those in
      controls throughout all clinical phases (p < 0.01). The highly elevated Serum
      sHLA-I concentrations peaked in the oliguric phase and declined gradually through
      the phases of HFRS. Serum sHLA-l concentrations in patients with hypotensive
      episode were higher than in those without the episode (5,85 +/-2,184 vs. 2,389 +/
      860 ng/ml in oliguric phase, 4.11 +/- 1,952 vs. 1,502 +/- 592 ng/ml in diuretic
      phase, p < 0.05), and serum sHLA-l levels showed a significant correlation with
      blood WBC count (r = 0.75 in the febrile and hypotensive phase, p < 0.01) and
      serum creatinine concentrations (r = 0.64 in the oliguric phase, p < 0.01),
      respectively, Urine sHLA-I levels in the oliguric phase were significantly higher
      than those in the diuretic phase (390 +/- 155 vs. 214 +/- 45 ng/mg Cr, p < 0.05)
      and urine sHLA-I levels are associated with severe illness in patients with HFRS.
      The higher serum sHLA-I are associated with severe illness in patients with HFRS.
      The persistent elevation of serum sHLA-I during all phases of HFRS might be
      related to increased production due to prolonged cellular immunologic stimulation
      by the Hantaan virus rather than decreased excretion of sHLA-I through the
      kidney. CONCLUSION: We suggest that the serum and urine sHLA-I concentrations can
      be used as a stable and objective parameter for monitoring clinical severity and
      renal dysfunction in patients with HFRS.

PMID- 9159039
TI  - Attenuated central pressor response to nitric oxide synthesis inhibition in
      chronic renal failure rats.
AB  - OBJECTIVES: Central and peripheral roles of nitric oxide (NO) in blood pressure
      regulation have been suggested. The present study was aimed at examining if the
      role of NO in blood pressure regulation is altered in chronic renal failure.
      METHODS: Blood pressure responses to acute inhibition of NO were examined in 5/6
      nephrectomized rats. Three weeks after the renal ablation, under thiopental (50
      mg/kg, i.p.) anesthesia, an intracerebroventricular cannula was placed in the
      left lateral ventricle and the femoral vein was cannulated to serve as an
      infusion route. The arterial blood pressure was measured in the right femoral
      artery. NG-nito-L-arginine methyl ester (L-NAME) was infused (100 microgram/kg
      per min for 60 min either intracerebroventricularly or intravenously. RESULTS:
      Chronic renal failure rats showed a significantly higher arterial pressure than
      the control rats (147 +/- 14 mmHg vs. 122 +/- 13 mmHg). Intracerebroventricular L
      NAME did not affect the arterial pressure in chronic renal failure rats (0.5 +/-
      4 mmHg increase from the basal), while it significantly increased the arterial
      pressure in normal rats (22 +/- 3 mmHg increases from the basal). Intravenous L
      NAME increased the arterial pressure, the magnitude of which did not differ
      between the normal and chronic renal failure rats (24 +/- 3 vs. 16 +/- 3 mmHg
      increases from the basal). CONCLUSION: These results indicate that the central
      role of NO in the regulation of blood pressure is altered in chronic renal
      failure.

PMID- 9159040
TI  - Changes of the plasma endothelin in adaptation to increased salt intake in rats.
AB  - OBJECTIVES: Roles for vascular endothelial hormones in body fluid balance have
      been variously suggested. The present study was aimed at investigating whether
      the plasma endothelin is altered in responses to acute and chronic perturbations
      in body fluid balance. METHODS: Effects of intravenous infusion of MG-nitro-L
      arginine methyl ester (L-NAME), a competitive inhibitor of endothelium-derived
      nitric oxide (NO) synthesis, on urinary excretion, blood pressure and plasma
      levels of endothelin were examined in rats kept on either normal or high-salt
      diet for two weeks. The plasma endothelin levels in response to an acute
      extracellular volume expansion (VE) were also determined in normal and 2-kidney,
      1 clip (2K1C) hypertensive rats. RESULTS: L-NAME (20 and 200 micrograms.kg(-1)
      per min) elicited diuretic and natriuretic effects in association with increased
      blood pressure both in normal and high-salt rats. In high-salt rats, however, the
      urinary response to L-NAME was attenuated and the pressor response was augmented
      compared with the control. High-salt intake per se caused a small, but
      significant, increase of the plasma endothelin. L-NAME (200 micrograms(-1) per
      min) markedly increased the plasma endothelin was also marginally increased
      following VE, the magnitude of which did not differ between the normal and 2K1C
      rats. CONCLUSION: These results suggest that the endothelin system takes part in
      adaptation to increased salt-intake. Another evidence indicating a negative
      modulation of NO on the release of endothelin is also provided.

PMID- 9159041
TI  - The effect of diphenyl-dimethyl-dicarboxylate on cyclosporine-A blood level in
      kidney transplants with chronic hepatitis.
AB  - An adequate blood level of cyclosporine-A (CsA) is essential to keep graft
      function in kidney transplants. Due to a narrow therapeutic index and highly
      variable pharmacokinetic properties associated with CsA, drug interactions may
      have a significant impact on the immunosuppressive efficacy or toxicity of CsA.
      Numerous drug interactions of potential clinical significance involving CsA have
      been reported. Dephenyl-dimethyl-dicarboxylate (PMC), a hepatotonic drug, is a
      substance derived from the synthesis of Schizandrae fructus elements. We have
      experienced two cases of drug interaction between CsA and PMC in kidney
      transplants with chronic hepatitis. In both cases, CsA troughs decreased markedly
      to a subtherapeutic level following administration of PMC. We, therefore, suggest
      that PMC could decrease the CsA trough level and thus a close monitoring of the
      CsA trough level is necessary during a PMC therapy.

PMID- 9159042
TI  - A case of bronchiolitis obliterans organizing pneumonia associated with
      adenovirus.
AB  - A 58-year-old man described a short history of dyspnea and a preceding flu like
      illness with roentgenographic features of an interstitial lung disease. An open
      lung biopsy specimen from him showed bronchiolitis obliterans with organizing
      pneumonia (BOOP). Adenovirus was isolated from a throat swab. There was both
      clinical and radiographic improvement with supportive care. We herein report a
      first case of BOOP associated with adenovirus in Korea.

PMID- 9159043
TI  - A case of carpal tunnel syndrome due to dialysis-related amyloidosis in a patient
      undergoing long-term hemodialysis.
AB  - Carpal tunnel syndrome (CTS) is characterized by burning pain, numbness and
      tingling sensation in the thumb, index and middle fingers and the lateral half of
      the palm and progressive atrophy of the thenar muscles by compression of the
      median nerve within the carpal tunnel due to a variety of etiologic factors.
      Surgical intervention usually successfully relieves symptoms of CTS. Recently CTS
      has been regarded as one of the major clinical manifestations of dialysis-related
      amyloidosis due to beta 2-microglobulin deposition and recognized with increasing
      frequency in patients undergoing long-term hemodialysis. We report a case of
      carpal tunnel syndrome due to dialysis-related amyloidosis in patients undergoing
      long-term hemodialysis, confirmed by electromyography and biopsy in transverse
      carpal ligament and median nerve.

PMID- 9159044
TI  - A case of coagulation factor V deficiency complicated with intracranial
      hemorrhage.
AB  - Factor V deficiency is a relatively uncommon disorder, inherited as an autosomal
      recessive trait that manifests clinically only in individuals who inherit the
      defective gene from both parents. The hemorrhage of nasal and oral cavity and
      ecchymosis are common but intracranial hemorrhage is very rare. We experienced a
      53 year old male patient with intracranial hemorrhage due to factor V deficiency.
      The laboratory tests showed prolongation of APTT and PT, normal bleeding time and
      normal thrombin time. The levels of the coagulation profiles on the patient
      revealed a significant decrease factor V, below 1% of normal range (60-140%).
      Other coagulation factors were normal. He was treated with fresh frozen plasma
      and completely recovered 3 weeks after treatment.

PMID- 9159045
TI  - A case of lymphomatoid papulosis occurred simultaneously with Ki-1-positive
      anaplastic large cell lymphoma.
AB  - Lymphomatoid papulosis (LyP) is a chronic self-healing skin eruption that is
      clinically benign but histologically mimics a malignant lymphoma. However,
      lymphomatoid papulosis with anaplastic large cell lymphoma responds poorly to
      medical treatments, including chemotherapies. We experienced a 60-year-old male
      patient with lymphomatoid papulosis occurred simultaneously with relapsed Ki-1
      positive anaplastic large cell lymphoma who was treated with salvage chemotherapy
      but, unfortunately, failed to be rescued. We report it with a review of the
      literature.

PMID- 9159046
TI  - Oncogenic osteomalacia caused by a phosphaturic mesenchymal tumor of the oral
      cavity: a case report.
AB  - We report a case of oncogenic osteomalacia associated with a phosphaturic
      mesenchymal tumor in a 31-year-old woman. She was presented with severe
      generalized bone and muscle pain and was restricted to bed. She lost 20 cm in
      height over the 8 years since she had first noticed a pain in her thigh. A walnut
      sized, hard, soft tissue tumor was found very easily beside her lower molar teeth
      Radiologic examination revealed a remarkable decrease in bone density and
      multiple pathologic fractures of spine, femur and phalangeal bones. Severe
      hypophosphatemia, hyperphosphaturia, low plasma 1,25-dihydroxyvitamin D3 level
      and high plasma PTH level were disclosed at presentation. Histomorphometric
      examination revealed an extensive area of unmineralized osteoid and little
      mineralizing activity. A pharmacologic dose of 1 alpha-hydroxyvitamin D3 or or
      1,25-dihydroxyvitamin D3 slightly increased the serum phosphate level and renal
      tubular reabsorption of phosphate, and slightly decreased plasma PTH level
      without any symptomatic improvement. Histologic examination of the tumor revealed
      a mixed connective tissue tumor that consisted of central woven bones and
      surrounding primitive spindle cells with prominent vascularities. After removal
      of the tumor, all biochemical, hormonal and radiologic abnormalities disappeared
      with remarkable symptomatic improvement.

PMID- 9159047
TI  - A case of idiopathic thyrotropin (TSH) deficiency.
AB  - The first case of idiopathic thyrotropin (TSH) deficiency in an old woman with
      thyroid functioning adenoma was reported. She got subtotal thyroidectomy before
      about four years of her admission to our hospital because of fatigability, puffy
      face and leg edema. At time, she had low TSH and free T4 levels despite
      replacement therapy with desiccated thyroid. No response of only serum TSH after
      administration of combined stimulant containing TRH and repeated TRH suggested
      the failure of TSH secretion. CT MRI did not show any abnormality. These results
      indicated that her hypothyroidism was due to acquired idiopathic TSH deficiency.

PMID- 9159048
TI  - A case of intraductal papillary tumor of pancreas associated with mucinous ductal
      ectasia.
AB  - Intraductal papillary neoplasm associated with mucinous ductal ectasia is an
      uncommon cystic disease of the pancreas. This tumor is characterized by the
      multilocular cyst lined by mucin producing cells with variable degrees of atypia
      and ductal ectasia. In addition, this tumor has a favorable prognosis in contrast
      to other mucinous cystic tumor of the pancreas. Reports on intraductal mucin
      producing tumor are quite limited and most of them are found in Japanese
      literature. We report a case of intraductal papillary adenocarcinoma with marked
      dilatation of the pancreatic duct filled with mucin in a 72-year-old female
      patient.

PMID- 9159049
TI  - Acute pancreatitis complicating pregnancy in a patient with co-existing
      choledochal cyst.
AB  - Choledochal cyst, although more common in females than in males, has only rarely
      been encountered in association with pregnancy. A 29-year-old nulliparous woman
      at 32nd week gestation was diagnosed as acute pancreatitis with co-existing type
      l choledochal cyst. Resection of the choledochal cyst was performed and a Roux-en
      Y hepatico-jeunostomy was carried out to provide biliary drainage. Although the
      preferred management of a choledochal cyst is excision and Roux-en Y
      reconstruction, this may have to be deferred until after delivery, depending on
      gestational age, because of the risk of fetal mortality and maternal morbidity
      that is associated with this procedure.

PMID- 9159051
TI  - Sunlight: an environmental toxin for humans. A primer to advise patients.
AB  - Sunlight causes acute toxic effects such as sunburn, local and systemic immune
      suppression, and long-term adverse effects including photoaging and skin cancer.
      The degree of damage depends on the overall exposure-dose and individual
      susceptibility. Various strategies should be employed to minimize sun-exposure
      damage, including proper use of sunscreens and exposure avoidance. Public
      education might best be focused on protecting children and promoting awareness of
      photoaging changes in adults.

PMID- 9159050
TI  - A case of biliary cystadenocarcinoma.
AB  - Biliary cystadenocarcinoma is a very rare cystic tumor that arises in the liver
      or, less frequently, in the extrahepatic biliary system. It has been shown to
      arise in congenital liver cysts, bile ducts, biliary cystadenoma, in the context
      of fibropolycystic disease and in the hepatoduodenal ligament. Common presenting
      symptoms include an abdominal mass, local pain, nausea, jaundice, fever or
      occasional ascites. Some patients are asymptomatic, the lesion being an
      incidental finding at autopsy or surgery. Approximately 50 cases have been
      reported in the literature. We report a case of biliary cystadenocarcinoma in a
      63-year-old man with a review of the literature.

PMID- 9159052
TI  - Mohs micrographic surgery for the treatment of difficult skin cancers.
AB  - Most skin cancers can be managed effectively using standard therapeutic methods.
      However, specific subsets of skin cancers--including tumors that are recurrent,
      large, or aggressive, along with tumors located at sites of functional and
      cosmetic concern--provide a significant therapeutic challenge. Mohs micrographic
      surgery offers the greatest potential cor cure of difficult tumors, while
      providing for maximal preservation of healthy tissue. This paper describes the
      history of Mohs surgery, the technique, and the indications for its use.

PMID- 9159053
TI  - Nonmelanoma skin cancer.
AB  - Nonmelanoma skin cancer is the most common cancer in the United States, and its
      incidence is increasing dramatically. Although mostly caused by sun exposure,
      less common causes are also discussed. Several types of basal cell carcinomas are
      described, as well as squamous cell carcinoma. While these carcinomas rarely
      cause death, they can be locally destructive, and removal can cause significant
      disfigurement and functional impairment. The value of early detection is
      emphasized.

PMID- 9159054
TI  - Atypical mole syndrome: a brief overview for the primary care physician.
AB  - Early detection of melanoma and identification of potential markers or precursor
      lesions can substantially improve survival. Several risk factors have been
      identified in the pathogenesis of this potentially lethal cancer. Numerous
      reports in the literature have confirmed a subset of persons with an increased
      risk of developing melanoma. These patients are identified by a distinctive
      clinical phenotype depicted by unusually appearing melanocytic nevi (moles) in
      association with an increased number of total body nevi. They may have a family
      history of atypical moles or melanoma. In order to facilitate the recognition of
      such individuals by the non-dermatologist, a brief overview and salient features
      of the atypical mole syndrome are presented.

PMID- 9159055
TI  - Diagnosis of pigmented skin lesions aided by epiluminescence microscopy.
AB  - Early diagnosis of superficial melanoma (Clark Level I, II) remains the best
      approach to reduce the death rate from this malignant neoplasm. Today's well
      informed patients understand the need to have changing moles evaluated. However,
      many benign pigmented lesions that undergo changes in appearance do not require
      excision. Epiluminescence microscopy can facilitate the differential diagnosis of
      cutaneous pigmented lesions and help determine which of these require biopsy.

PMID- 9159056
TI  - The surgical management of invasive primary melanoma: an update.

PMID- 9159057
TI  - Uncommon cutaneous neoplasms.

PMID- 9159058
TI  - Preventing epidemics with age-specific vaccination schedules.
AB  - A method is proposed for computing the coverage required to prevent epidemics by
      age-specific vaccination schedules. The method applies in a very general setting
      and provides explicit expressions in many cases. It can accommodate vaccination
      doses administered at different ages, heterogeneity among individuals of
      different ages, a community structured into households, and waning of vaccine
      induced immunity. A comparison of results for two specific community settings,
      with analogous parameter values, indicates that the immunity coverage required to
      prevent epidemics in a community of households is less than that required for a
      community of uniformly mixing individuals.

PMID- 9159059
TI  - Effective population size for a sex-linked locus in populations under selection.
AB  - The problem of selection in the prediction of effective population size for a sex
      linked locus was addressed in terms of the cumulative effect of selection on
      change in frequency of a sex-linked neutral gene. To express the cumulative
      effect of selection, a transition matrix approach was used. It was found that the
      terms accounting for the cumulative change in gene frequency show different
      expressions, depending on the gametic pathways. This dependency is due to the
      fact that the heterogametic sex transmits a sex-linked gene only to offspring of
      the homogametic sex, whereas the homogametic sex transmits to offspring of both
      sexes. Monte Carlo simulation was carried out to check the obtained prediction
      equation. The result showed that there is a good agreement between observed and
      predicted effective sizes.

PMID- 9159061
TI  - Do cells repair precancerous lesions induced by radiation?
AB  - The most widely accepted point of view is that cells are endowed with the
      capacity to repair the primary lesions responsible for cancer induction. In
      radiobiology, this popular belief evolved from experiments of the same type as
      those that suggested the existence of sublethal radiation damage repair. The
      central problem with such data is that the cell-killing component of radiation
      damage may mask the effects associated with repair of precancerous lesions. The
      challenge is to separate the two processes that contribute to the observed tumor
      incidence after irradiation. using a recently developed stochastic model of
      radiation carcinogenesis allowing for cell death, we provide evidence that
      precancerous lesions are not subject to repair under certain experimental
      conditions.

PMID- 9159060
TI  - Biological growth on a surface.
AB  - A new biological growth model is introduced. After random selection of possible
      growth sites, cells are added in an allowable random direction. Unlike the Eden
      model, the current model is grid independent and can be adapted to any curved
      surface. Growths of colonies of as many as 10(5) cells are simulated on planar,
      cylindrical, and spherical surfaces. It is found that the interior density is
      constant, whereas the boundary is fractal.

PMID- 9159062
TI  - Pain and ideology in human and veterinary medicine.
AB  - Historically, physicians and veterinarians have placed much less emphasis on felt
      pain than ordinary citizens do. This is, in part, a function of the philosophical
      and valuational presuppositions accompanying the development of modern
      reductionistic Newtonian Science. In the 20th century, these presuppositions were
      hardened into an ideology affirming that science (and medicine) could not deal
      with the subjective experience or make value judgments, including ethical
      judgments. Control of felt pain, and the moral imperative favoring such control,
      were both bracketed by this ideology. With recent major changes in social ethics,
      however, and with recent realizations that pain is biologically active, both
      human and veterinary medicine can no longer ignore the moral and medical
      dimensions of felt pain.

PMID- 9159063
TI  - Through a glass darkly: using behavior to assess pain.
AB  - Behavior assessment is crucial to the process of evaluation of pain and
      discomfort in veterinary patients. Behavioral responses to pain and other
      stressors are a function of the interaction between the individual and its
      environment, and are influenced by many factors including species, breed, age,
      sex, source of pain, and coexisting disease. Behavioral changes associated with
      acute postoperative pain typically peak within 24 hours and wane progressively
      thereafter. The intensity and duration of postoperative pain correlate with the
      location and extent of tissue injury, but there is much inter-patient variation
      of each characteristic. Published methods of systematic evaluation of pain in
      animals include objective measures of physiologic responses to experimental pain,
      subjective or semi-objective assessment of postoperative behavior, and
      quantitative measures of postoperative behavior and physiology. The techniques of
      quantitative measures of behavior are similar to pain-rating instruments
      developed for use in young children. Although objective assessment tools are
      difficult to develop and time consuming to apply, their methodological rigor and
      objectivity allow evaluation of behavior with minimal observer bias. Until
      objective assessment tools become widely used clinically, the best approach is to
      actively seek out evidence of pain in our patients, assuming its presence
      whenever there is tissue injury or inflammation.

PMID- 9159064
TI  - Recent advances in our understanding of pain: how should they affect management?
AB  - Pain management continues to challenge the clinical veterinarian. It is important
      to appreciate that pain is not a monolithic syndrome; many variables associated
      with pain origin, transmission, perception, and response must be understood in
      order to provide the best pain relief in a clinical patient. Rational pain
      management requires an understanding of underlying mechanisms involved in pain
      and an appreciation of how analgesic agents act to disrupt them. The goal of this
      presentation is to acquaint you with the fundamentals associated with pain
      physiology and how clinical pain management may modify these mechanisms to
      benefit the patient.

PMID- 9159065
TI  - Principles of analgesic drug therapy.
AB  - The drugs most often used for pain relief in animals are the nonsteroidal
      antiinflammatory drugs (NSAIDS) and the opioid analgesics. The NSAIDS are
      effective, inexpensive, and long-acting drugs, but their degree of analgesia is
      limited by the adverse effects at high doses. The most common adverse effect from
      NSAIDS is gastritis and gastrointestinal hemorrhage and ulceration. This is most
      common from high doses, or from using NSAIDS not appropriate for dogs such as
      ibuprofen or indomethacin. The NSAIDS used in dogs include aspirin,
      phenylbutazone, naproxen, piroxicam, ketoprofen, and carprofen. Carprofen is a
      new drug with a low incidence of side effects and its popularity is increasing at
      a fast rate. For more acute pain, especially acute pain from surgery or trauma,
      opioids are frequently administered. Opioids have the advantage of higher
      efficacy when the dose is increased. The incidence of adverse effects is low, but
      side effects of sedation are common. An important disadvantage of opioids is
      their short duration and low oral absorption, which necessitates a frequent
      injection or i.v. infusion for most patients. Recent studies have established
      other applications for administration of opioids such as a transdermal fentanyl
      patch. These applications offer new possibilities for convenient administration.

PMID- 9159066
TI  - Local and regional anesthesia and analgesia.
AB  - Many benefits can be obtained from the use of drugs applied locally or regionally
      when treating dogs and cats that are in pain or will be in pain because of
      surgical trauma. These techniques often use less medication than for systemic
      administration with a reduction in the likelihood of toxic effects from these
      compounds. Complete relief of pain can be achieved by blocking nerves originating
      from the site of injury by using local anesthetics, but this may entail loss of
      all sensation and motor paralysis. Other drugs, such as the opioids, may decrease
      the nociceptive input with minimal effect on motor activity. This report
      discusses the use of local anesthetics and other drugs for analgesia of the skin,
      mucous membranes, joints, pleura, and peritoneum, and the application of these
      drugs for regional blocks of peripheral nerves and epidural/intrathecal
      injection.

PMID- 9159068
TI  - Management of pain in the critically ill patient.
AB  - In spite of growing evidence that effective pain management of critically ill
      human beings decreases their morbidity and mortality, pain is often undertreated
      in critically ill animals. Reasons for withholding analgesics in these animals
      have included fear of contributing to cardiopulmonary instability and difficulty
      in monitoring response to therapy. Appropriately used, analgesics improve the
      status of critically ill animals. Opioids are the most widely used analgesics but
      other options exist. Newer methods of analgesic administration include continuous
      infusions, epidural, local, regional, and transdermal administration.

PMID- 9159067
TI  - Management of acute and surgical pain.
AB  - Effective treatment of acute pain secondary to surgery and trauma is often a
      complex and perplexing task. Concern about potential adverse effects of analgesic
      drugs on cardiovascular, respiratory, renal, and central nervous system functions
      often limits the use of analgesics in the very patients that could benefit from
      them the most. Combining drugs of different classes and with different mechanisms
      of action is an established anesthesia technique used to achieve a desired effect
      with a minimum of adverse side effects. Similarly, the use of a balanced or
      multimodal approach to the treatment of acute pain can greatly enhance the
      clinician's ability to safely provide effective analgesia. Systemic opioids,
      alpha-2 agonists, nonsteroidal antiinflammatory drugs, and local or regional
      analgesic techniques can be used in varying combinations to meet the needs of the
      painful animal and hasten recovery.

PMID- 9159069
TI  - Chronic pain: osteoarthritis and cancer.
AB  - Osteoarthritis and cancer pain are two types of chronic pain commonly seen in
      small animal practice. The management of osteoarthritic pain consists of both
      pharmacologic therapy and nonpharmacologic strategies, including exercise
      control, dietary management and surgical therapy. Nonsteroidal antiinflammatory
      drugs are commonly used, although there is still controversy about their effect
      on the underlying pathologic processes of osteoarthritis. Despite a lack of well
      designed clinical trials, chondroprotective drugs and neutraceuticals have gained
      popularity. Cancer pain can result from direct tumor invasion, paraneoplastic
      syndromes or diagnostic and therapeutic procedures, including surgery,
      chemotherapy and radiation. Treatment of cancer pain consists of definitive or
      palliative therapy and management of therapy induced pain. Analgesic therapy
      should be based on the World Health Organization's three step analgesic ladder
      for the administration of analgesia to cancer patients.

PMID- 9159070
TI  - Narcotic regulation in the United States: taking the pain out of analgesic
      therapy.
AB  - Maintaining accurate controlled substance records need not deter a veterinarian
      from obtaining and using opiate analgesics and anesthetics. Paperwork and
      behavior requirements for ordering, receiving, storing, administering,
      dispensing, and prescribing controlled substances are described in detail.
      Important regulatory information resources are also listed.

PMID- 9159072
TI  - Mammalian RNA-dependent deaminases and edited mRNAs.
AB  - The past year has witnessed major progress in the field of mammalian nuclear RNA
      editing. Two new sequence-related RNA-dependent adenosine deaminases, distantly
      related to the previously characterized double-stranded RNA adenosine deaminase
      DRADA/dsRAD, have been molecularly characterized. One of these deaminases edits
      in vitro with precision for the molecular determinant that controls the Ca2+
      permeability of fast synaptic glutamate-gated cation channels. This deaminase,
      like DRADA, is expressed in many tissues and the search is now on for more
      substrates of these RNA-editing enzymes. Moreover, the physiological role of the
      apolipoprotein B RNA editing enzyme APOBEC-1 has been investigated in genetically
      manipulated mice.

PMID- 9159071
TI  - Molecular model for telomeric heterochromatin in yeast.
AB  - A molecular model for the formation of yeast core telomeric heterochromatin has
      been proposed recently. The RAP1 protein provides the specificity for the
      localization of heterochromatin through its recognition of telomeric DNA
      sequences. Its complexing with silencing information regulators (SIR2, SIR3 and
      SIR4) and histones H3 and H4 generates a folded-back DNA structure. This not only
      represses adjacent genes through SIR-protein-histone interactions, but also
      enables condensation and protection of the telomeric end. The SIR2 and SIR4
      levels at the core differ from those in the extended telomeric heterochromatin
      produced when the limiting protein, SIR3, is overexpressed.

PMID- 9159073
TI  - The cytoskeleton in mRNA localization and cell differentiation.
AB  - Asymmetric distribution of cytoplasmic proteins and messenger RNAs has been
      implicated in several instances of cell differentiation. Microtubules have been
      suggested to direct mRNA localization in Drosophila and Xenopus oocytes but motor
      proteins that might transport mRNAs have not yet been identified. Recent data
      imply that in Drosophila, Caenorhabditis elegans and budding yeast, proteins of
      the actin cytoskeleton, including unconventional myosins, play active roles in
      the segregation of differentiation factors and mRNAs.

PMID- 9159074
TI  - Nuclear organization and gene expression: homologous pairing and long-range
      interactions.
AB  - Genetic studies have demonstrated that pairing interactions between homologous
      chromosomes and long-range associations between nonhomologous sites can influence
      gene expression. Recent work has revealed that such influences are widespread in
      eukaryotes and that chromosome architecture is likely to be of fundamental
      importance for nuclear structure and function.

PMID- 9159075
TI  - Common themes in the function of transcription and splicing enhancers.
AB  - Regulation of both transcription and RNA splicing requires enhancer elements,
      that is, cis-acting DNA or RNA sequences that promote the activities of linked
      promoters or splice sites, respectively. Both types of enhancer associate with
      regulatory proteins to form multicomponent enhancer complexes that recruit the
      necessary enzymatic machinery to promoter or splice site recognition sequences.
      This recruitment occurs as a result of direct interactions between regulatory
      proteins in the enhancer complexes and components of the basic enzymatic
      machineries. Recent advances suggest that the high degree of regulatory
      specificity observed for both transcription and splicing is due, in large part,
      to the multicomponent nature of enhancer complexes and to their cooperative
      assembly.

PMID- 9159076
TI  - RNA polymerase II holoenzyme and transcriptional regulation.
AB  - RNA polymerase II holoenzymes isolated from yeast and mammalian cells are large,
      preassembled complexes that contain some or all of the general transcription
      initiation factors and many other polypeptides. Recent experiments suggest that
      these holoenzymes may mediate alterations in chromatin structure and play a key
      role in regulatory mechanisms that influence transcriptional initiation, RNA
      chain elongation, RNA processing and transcription termination.

PMID- 9159077
TI  - Cyclin-dependent kinase and initiation at eukaryotic origins: a replication
      switch?
AB  - A growing body of evidence indicates that cyclin-dependent kinases (CDKs)
      regulate the activity of eukaryotic origins of replication both positively and
      negatively. Although the details of this control remain unclear, recent work
      suggests that CDKs act directly at origins, where they associate with and
      phosphorylate several key initiator proteins. These data suggest that a CDK
      regulated replication switch operates at each origin to ensure that initiation
      occurs precisely once per cell cycle.

PMID- 9159078
TI  - Post-transcriptional gene silencing in plants.
AB  - Overexpression of chimeric transgenes in plants can trigger post-transcriptional
      gene silencing that is dependent on epigenetic information and physiological
      conditions. The current view is that unproductive RNA serves as a crucial signal
      for gene silencing, although direct evidence is lacking for this theory. A
      signalling cascade then leads to strongly enhanced turnover of all RNAs that
      share a critical degree of sequence similarity. The molecular details of the
      mechanism are, however, insufficiently understood to explain the phenomenon
      completely and to comprehend its biological significance.

PMID- 9159079
TI  - Function and synthesis of small nucleolar RNAs.
AB  - Eukaryotic cells contain an extraordinarily complex population of small nucleolar
      RNAs (snoRNAs). During its brief lifetime, each human pre-rRNA molecule will
      transiently associate with approximately 150 different snoRNA species. In the
      past year our understanding of snoRNAs has been clarified by the recognition that
      the snoRNA population can be divided into a small number of groups which are
      structurally and functionally distinct. The two largest groups of snoRNAs direct
      the site-specific modification of the pre-rRNA at positions of 2'-O-methylation
      and pseudouridine formatio. Other groups of snoRNAs function in pre-rRNA cleavage
      and in the formation of the correct structure of the pre-rRNA.

PMID- 9159080
TI  - Protein functions in pre-mRNA splicing.
AB  - Proteins have been implicated in an expanding variety of functions during pre
      mRNA splicing. Molecular cloning has identified genes encoding spliceosomal
      proteins that potentially act as novel RNA helicases, GTPases, or protein
      isomerases. Novel protein-protein and protein-RNA interactions that are required
      for functional spliceosome formation have also been described. Finally, growing
      evidence suggests that proteins may contribute directly to the spliceosome's
      active sites.

PMID- 9159081
TI  - Nuclear protein import.
AB  - The defining feature of eukaryotic organisms is the cell nucleus. All nuclear
      proteins are synthesized in the cytoplasm and need to be imported through the
      nuclear pore complexes (NPCs) into the nucleus. Import can be directed by various
      signals, of which the classical nuclear localization signal (NLS) and the M9
      import signal are the best characterized. The past year has provided insight into
      the functions of the key players in NLS- and M9-dependent import, the
      interactions of these key players and possible implications of these interactions
      for the import mechanism. Although an understanding of some of the steps in the
      import process is emerging, the molecular mechanism of the actual translocation
      through the NPC is still obscure.

PMID- 9159082
TI  - A comparison of mammalian and yeast pre-mRNA 3'-end processing.
AB  - Many components of the mammalian and yeast pre-mRNA 3'-end-processing machinery
      have recently been purified and cDNAs or genes coding for these factors have been
      cloned. Most of the factors consist of multiple subunits, some of which serve to
      bind the RNA substrate, others of which are involved in forming a complex network
      of protein-protein interactions. Most of the mammalian 3'-end-processing factors
      are similar in their amino acid sequence to the yeast factors, indicating that
      they have a common evolutionary history.

PMID- 9159083
TI  - Nuclear export of proteins and RNAs.
AB  - Our understanding of protein export from the nucleus to the cytoplasm has been
      advanced recently by the discovery of active, signal-mediated export pathways.
      Nuclear export signals have been identified in several proteins, the majority of
      which are RNA-binding proteins. Nuclear export of RNA molecules is likely to be
      driven by protein-based nuclear export signals.

PMID- 9159084
TI  - The complex pathology of trinucleotide repeats.
AB  - The expansion of trinucleotide repeat sequences has now been shown to be the
      underlying cause of at least ten human disorders. Unifying features among these
      diseases include the unstable behavior of the triplet repeat during germline
      transmission when the length of the repeat exceeds a critical value. However, the
      trinucleotide repeat disorders can be divided into two distinct groups. Type I
      disorders involve the expansion of CAG repeats, which encode an expanded
      polyglutamine, inserted into the open-reading frame of a gene that is usually
      quite broadly expressed. Recently, mouse models for type I disorders have been
      developed and the basis of pathology is under study, both in these models and
      through biochemical and cell biological approaches. The type II disorders involve
      repeat expansions in noncoding regions of genes. The mechanisms by which these
      repeat expansions lead to pathology may be quite diverse.

PMID- 9159085
TI  - Nucleus and gene expression.

PMID- 9159086
TI  - From nucleoporins to nuclear pore complexes.
AB  - One of the largest supramolecular assemblies in the eukaryotic cell, the nuclear
      pore complex, is now being dissected into its numerous molecular constituents.
      The combined use of biochemistry and genetics in yeast has made this rapid
      development possible. Although less is known about vertebrate nucleoporins, the
      first clues are now emerging about their in vivo function also. Much remains to
      be learned about nuclear pore complex assembly and function, however.

PMID- 9159087
TI  - Web alert. Nucleus and gene expression.

PMID- 9159088
TI  - Time matters.

PMID- 9159089
TI  - The battle against the Sacred disease heats up: recent advances in the
      understanding and treatment of epilepsies.

PMID- 9159090
TI  - Circulation and hemodynamics.

PMID- 9159091
TI  - Clinical nephrology.

PMID- 9159092
TI  - Gynaecological oncology.

PMID- 9159093
TI  - Gynaecological pathology.

PMID- 9159094
TI  - Orthopedics.

PMID- 9159095
TI  - A memory of Frank A. Oski.

PMID- 9159096
TI  - Systemic disorders with rheumatic manifestations.

PMID- 9159097
TI  - Discussion of "The evaluation of forensic DNA evidence".

PMID- 9159098
TI  - Bacteria gone native vs. bacteria gone awry?: plasmidic transfer and bacterial
      evolution.

PMID- 9159099
TI  - Creeping walls, softening fruit, and penetrating pollen tubes: the growing roles
      of expansins.

PMID- 9159100
TI  - Molecular linguistics: extracting information from gene and protein sequences.

PMID- 9159101
TI  - Transport bicycles.

PMID- 9159103
TI  - The bi-loop, a new general four-stranded DNA motif.
AB  - The crystal structure of the cyclic octanucleotide d<pATTCATTC> contains two
      independent molecules that form a novel quadruplex by means of intermolecular
      Watson-Crick A.T pairs and base stacking. A virtually identical quadruplex
      composed of G.C pairs was found by earlier x-ray analysis of the linear heptamer
      d(GCATGCT), when the DNA was looped in the crystal. The close correspondence
      between these two structures of markedly dissimilar oligonucleotides suggests
      that they are both examples of a previously unrecognized motif. Their nucleotide
      sequences have little in common except for two separated 5'-purine-pyrimidine
      dinucleotides forming the quadruplex, and by implication these so-called "bi
      loops" could occur widely in natural DNA. Such structures provide a mechanism for
      noncovalent linking of polynucleotides in vivo. Their capacity to associate by
      base stacking, demonstrated in the crystal structure of d(GCATGCT), creates a
      compact molecular framework made up of four DNA chains within which strand
      exchange could take place.

PMID- 9159104
TI  - Alternative splicing of the human diacylglycerol kinase zeta gene in muscle.
AB  - Diacylglycerol can function as a second messenger, and one mechanism for the
      attenuation of this signal is its conversion to phosphatidic acid, which is
      catalyzed by diacylglycerol kinase (DGK). We screened a cDNA library from human
      skeletal muscle and isolated two DGKzeta cDNAs that differed from the 3.5-kb
      clone originally identified in endothelial cells. One transcript, which was 3.4
      kb long, was shown to be nonfunctional; it had a 77-bp deletion that included the
      translation initiation site. The other was 4.1 kb long with a unique 5' sequence
      of 853 bp. We also isolated a genomic clone of DGKzeta and determined its
      organization and location; it contains 32 exons, spans approximately 50 kb of
      genomic sequence, and maps to chromosome 11p11.2. The protein encoded by the 4.1
      kb transcript contains two cysteine-rich regions, a catalytic domain, and ankyrin
      repeats like the endothelial form of DGKzeta, as well as a unique N-terminal
      domain. The coding sequence was shown to be derived from alternative splicing of
      the DGKzeta gene. In cells transfected with the 4.1-kb clone, we detected a 130
      kDa protein with an antibody to DGKzeta and demonstrated that it was localized
      predominantly in the nucleus. We conclude that alternative splicing generates
      tissue-specific variants of DGKzeta that share some properties but may have
      unique ones as well.

PMID- 9159105
TI  - Design of polydactyl zinc-finger proteins for unique addressing within complex
      genomes.
AB  - Zinc-finger proteins of the Cys2-His2 type represent a class of malleable DNA
      binding proteins that may be selected to bind diverse sequences. Typically, zinc
      finger proteins containing three zinc-finger domains, like the murine
      transcription factor Zif268 and the human transcription factor Sp1, bind nine
      contiguous base pairs. To create a class of proteins that would be generally
      applicable to target unique sites within complex genomes, we have utilized
      structure-based modeling to design a polypeptide linker that fuses two three
      finger proteins. Two six-fingered proteins were created and demonstrated to bind
      18 contiguous bp of DNA in a sequence-specific fashion. Expression of these
      proteins as fusions to activation or repression domains allows transcription to
      be specifically up- or down-modulated within human cells. Polydactyl zinc-finger
      proteins should be broadly applicable as genome-specific transcriptional switches
      in gene therapy strategies and the development of novel transgenic plants and
      animals.

PMID- 9159106
TI  - Early embryonic lethality caused by targeted disruption of the mouse
      selenocysteine tRNA gene (Trsp).
AB  - Selenoprotein biosynthesis is mediated by tRNASec, which inserts selenocysteine
      at UGA codons in a complex, context-specific manner. This opal suppressor serves
      in the conversion of serine to selenocysteine as well. The mouse tRNASec gene
      (Trsp) maps to a proximal segment of chromosome 7. We constructed mice carrying a
      targeted deletion of the Trsp gene. The heterozygous mutants were viable,
      fertile, and appeared normal. Although the level of tRNASec was reduced to about
      50%-80% of the wild type in most organs, one of the selenoproteins, glutathione
      peroxidase, remained unaffected in the levels of its mRNA, protein, and enzyme
      activity, indicating that the haploid amount of tRNASec is not limiting in its
      biosynthesis. In contrast, the homozygous mutants died shortly after
      implantation, and the embryos were resorbed before 6.5 days post coitum. When the
      preimplantation embryos were placed in culture, however, the trophoectoderm cells
      showed outgrowths and the inner cell mass cells of the homozygous embryos were
      able to proliferate. These results indicate that Trsp expression is essential for
      early development of the embryo, and its lack causes peri-implantation lethality.
      However, the lethality does not appear to be due to a cell-autonomous function of
      tRNASec.

PMID- 9159107
TI  - Protein folding: how the mechanism of GroEL action is defined by kinetics.
AB  - We propose a mechanism for the role of the bacterial chaperonin GroEL in folding
      proteins. The principal assumptions of the mechanism are (i) that many unfolded
      proteins bind to GroEL because GroEL preferentially binds small unstructured
      regions of the substrate protein, (ii) that substrate protein within the cavity
      of GroEL folds by the same kinetic mechanism and rate processes as in bulk
      solution, (iii) that stable or transient complexes with GroEL during the folding
      process are defined by a kinetic partitioning between formation and dissociation
      of the complex and the rate of folding and unfolding of the protein, and (iv)
      that dissociation from the complex in early stages of folding may lead to
      aggregation but dissociation at a late stage leads to correct folding. The
      experimental conditions for refolding may play a role in defining the function of
      GroEL in the folding pathway. We propose that the role of GroES and MgATP, either
      binding or hydrolysis, is to regulate the association and dissociation processes
      rather than affecting the rate of folding.

PMID- 9159108
TI  - A molecular mechanism for energy coupling in a membrane transport protein, the
      lactose permease of Escherichia coli.
AB  - A mechanism for the coupled translocation of substrate and H+ by the lactose
      permease of Escherichia coli is proposed, based on a variety of experimental
      observations. The permease is composed of 12 alpha-helical rods that traverse the
      membrane with the N and C termini on the cytoplasmic face. Four residues are
      irreplaceable with respect to coupling, and the residues are paired-Arg-302
      (helix IX) with Glu-325 (helix X) and His-322 (helix X) with Glu-269 (helix
      VIII). In an adjacent region of the molecule at the interface between helices
      VIII and V is the substrate translocation pathway. Because of this arrangement,
      interfacial changes between helices VIII and V are transmitted to the interface
      between helices IX and X and vice versa. Upon ligand binding, a structural change
      at the interface between helices V and VIII disrupts the interaction between Glu
      269 and His-322, Glu-269 displaces Glu-325 from Arg-302, and Glu-325 is
      protonated. Simultaneously, protonated Glu-325 becomes inaccessible to water,
      which drastically increases its pKa. In this configuration, the permease
      undergoes a freely reversible conformational change that corresponds to
      translocation of the ternary complex. To return to ground state after release of
      substrate, the Arg-302-Glu-325 interaction must be reestablished, which
      necessitates loss of H+ from Glu-325. The H+ is released into a water-filled
      crevice between helices IX and X which becomes transiently accessible to both
      sides of the membrane due to a change in helix tilt, where it is acted upon
      equally by either the membrane potential or the pH gradient across the membrane.

PMID- 9159109
TI  - Host regulation of lysogenic decision in bacteriophage lambda: transmembrane
      modulation of FtsH (HflB), the cII degrading protease, by HflKC (HflA).
AB  - The cII gene product of bacteriophage lambda is unstable and required for the
      establishment of lysogenization. Its intracellular amount is important for the
      decision between lytic growth and lysogenization. Two genetic loci of Escherichia
      coli are crucial for these commitments of infecting lambda genome. One of them,
      hflA encodes the HflKC membrane protein complex, which has been believed to be a
      protease degrading the cII protein. However, both its absence and overproduction
      stabilized cII in vivo and the proposed serine protease-like sequence motif in
      HflC was dispensable for the lysogenization control. Moreover, the HflKC protein
      was found to reside on the periplasmic side of the plasma membrane. In contrast,
      the other host gene, ftsH (hflB) encoding an integral membrane ATPase/protease,
      is positively required for degradation of cII, since loss of its function
      stabilized cII and its overexpression accelerated the cII degradation. In vitro,
      purified FtsH catalyzed ATP-dependent proteolysis of cII and HflKC antagonized
      the FtsH action. These results, together with our previous finding that FtsH and
      HflKC form a complex, suggest that FtsH is the cII degrading protease and HflKC
      is a modulator of the FtsH function. We propose that this transmembrane
      modulation differentiates the FtsH actions to different substrate proteins such
      as the membrane-bound SecY protein and the cytosolic cII protein. This study
      necessitates a revision of the prevailing view about the host control over lambda
      lysogenic decision.

PMID- 9159111
TI  - Skn-1: evidence for a bipartite recognition helix in DNA binding.
AB  - Skn-1 is a maternally expressed transcription factor that specifies the fate of
      certain blastomeres early in the development of Caenorhabditis elegans. This
      transcription factor contains a basic region, but it binds to DNA as a monomer.
      Because other transcription factors containing basic regions bind as dimers, this
      finding implied that Skn represents a new DNA recognition motif. It has been
      proposed that the basic region helix of Skn is stabilized for binding by tertiary
      contacts to other parts of the protein. We have tested this proposal by carrying
      out circular dichroism (CD) and NMR experiments on the Skn domain and five
      truncated proteins. Our results have shown that the basic region of Skn is
      unstructured in solution and does not contact other parts of the protein; like
      other basic region peptides, it folds into a helix only upon binding specifically
      to DNA. However, there is a stably folded helical module in the Skn domain, and
      one of the helices in this module terminates immediately before the start of the
      basic region. This pre-organized helix contains a surface rich in basic amino
      acids, and we propose that this helix contacts the DNA distal to the basic region
      proper, providing an extra long helical recognition surface which helps to
      stabilize monomeric binding. Homology between the Skn domain and several basic
      region leucine zipper (bZIP) domains raises the possibility that the affinity and
      perhaps the specificity of DNA binding by bZIP proteins can be modulated by
      incorporating a stably folded helical segment that contacts the DNA just below
      the basic region proper.

PMID- 9159110
TI  - Copper-mediated repression of the activation domain in the yeast Mac1p
      transcription factor.
AB  - The expression of a number of genes encoding products involved in copper ion
      uptake in yeast is specifically inhibited by copper ions. We show here that
      copper metalloregulation occurs through Cu-dependent repression of the
      transactivation activity of Mac1p. A segment of the yeast transcription factor
      Mac1p was identified that activated transcription in vivo in a heterologous
      system using fusion polypeptides with the yeast Gal4 DNA-binding domain. The
      Gal4/Mac1p hybrid exhibits transactivation activity that is repressed in cells
      cultured in the presence of copper salts and derepressed in cells with reduced
      copper uptake. The repressive effect is specific for copper ions. The
      concentration dependency of the Cu-inactivation of Gal4/Mac1p is similar to that
      of Cu-inhibition of CTR1 expression, a known Cu-regulated gene in vivo. Copper
      inhibition of gene expression is not observed with a Gal4/Mac1p chimera
      containing the MAC1(up1) substitution within the transactivation domain. Cells
      harboring the MAC1(up1) allele fail to attenuate FRE1 and CTR1 expression in a Cu
      dependent manner. Additional MAC1(up) alleles exist within the first of two
      cysteine-rich sequence motifs adjacent to the His --> Gln MAC1(up1) encoded
      substitution. Thus, Cu-regulation of Mac1p function arises from a novel Cu
      specific repression of the transactivation domain function. Models for the
      mechanism of Cu-repression of Mac1p function will be discussed.

PMID- 9159112
TI  - Construction of a catalytically active iron superoxide dismutase by rational
      protein design.
AB  - The rational protein design algorithm DEZYMER was used to introduce the active
      site of nonheme iron superoxide dismutase (SOD) into the hydrophobic interior of
      the host protein, Escherichia coli thioredoxin (Trx), a protein that does not
      naturally contain a transition metal-binding site. Reconstitution of the designed
      protein, Trx-SOD, showed the incorporation of one high-affinity metal-binding
      site. The electronic spectra of the holoprotein and its N3- and F- adducts are
      analogous to those previously reported for native {Fe3+}SOD. Activity assays
      showed that {Fe3+}Trx-SOD is capable of catalyzing the dismutation of the
      superoxide anion; comparative studies with the unrelated wild-type E. coli iron
      SOD indicated that {Fe3+}Trx-SOD catalyzes the dismutation reaction at a rate on
      the order of 10(5) M-1s -1. The ability to design catalytically competent
      metalloenzymes allows for the systematic investigation of fundamental mechanistic
      questions concerning catalysis at transition metal centers.

PMID- 9159113
TI  - Characterization of the thyroid Na+/I- symporter with an anti-COOH terminus
      antibody.
AB  - The Na+/I- symporter (NIS) is the plasma membrane protein that catalyzes active I
      transport in the thyroid, the first step in thyroid hormone biogenesis. The cDNA
      encoding NIS was recently cloned in our laboratory and a secondary structure
      model proposed, suggesting that NIS is an intrinsic membrane protein (618 amino
      acids; approximately 65.2 kDa predicted molecular mass) with 12 putative
      transmembrane domains. Here we report the generation of a site-directed
      polyclonal anti-COOH terminus NIS antibody (Ab) that immunoreacts with a
      approximately 87 kDa-polypeptide present in membrane fractions from a rat thyroid
      cell line (FRTL-5). The model-predicted cytosolic-side location of the COOH
      terminus was confirmed by indirect immunofluorescence experiments using anti-COOH
      terminus NIS Ab in permeabilized FRTL-5 cells. Immunoreactivity was competitively
      blocked by the presence of excess synthetic peptide. Treatment of membrane
      fractions from FRTL-5 cells, Xenopus laevis oocytes, and COS cells expressing NIS
      with peptidyl N-glycanase F converted the approximately 87 kDa-polypeptide into a
      approximately 50 kDa-species, the same relative molecular weight exhibited by NIS
      expressed in E. coli. Anti-NIS Ab immunoprecipitated both the NIS precursor
      molecule (approximately 56 kDa) and the mature approximately 87 kDa form.
      Furthermore, a direct correlation between circulating levels of thyroid
      stimulating hormone and NIS expression in vivo was demonstrated.

PMID- 9159115
TI  - I2B is a small cytosolic protein that participates in vacuole fusion.
AB  - Saccharomyces cerevisiae vacuole inheritance requires two low molecular weight
      activities, LMA1 and LMA2. LMA1 is a heterodimer of thioredoxin and protease B
      inhibitor 2 (I2B). Here we show that the second low molecular weight activity
      (LMA2) is monomeric I2B. Though LMA2/I2B was initially identified as a protease B
      inhibitor, this protease inhibitor activity is not related to its ability to
      promote vacuole fusion: (i) Low Mr protease B inhibitors cannot substitute for
      LMA1 or LMA 2, (ii) LMA1 and LMA2 promote the fusion of vacuoles from a strain
      that has no protease B, (iii) low concentrations of LMA2 that fully inhibit
      protease B do not promote vacuole fusion, and (iv) LMA1, in which I2B is
      complexed with thioredoxin, is far more active than LMA2/I2B in promoting vacuole
      fusion and far less active in inhibiting protease B. These studies establish a
      new function for I2B.

PMID- 9159114
TI  - Both an N-terminal 65-kDa domain and a C-terminal 30-kDa domain of SecA cycle
      into the membrane at SecYEG during translocation.
AB  - SecA, a 102-kDa hydrophilic protein, couples the energy of ATP binding to the
      translocation of preprotein across the bacterial inner membrane. SecA function
      and topology were studied with metabolically labeled [35S]SecA and with inner
      membrane vesicles from cells that overexpressed SecYEGDFyajC, the integral domain
      of preprotein translocase. During translocation in the presence of ATP and
      preprotein, a 65-kDa N-terminal domain of SecA is protected from proteolytic
      digestion through insertion into the membrane, as previously reported for a 30
      kDa C-terminal domain [Economou, A. & Wickner, W. (1994) Cell 78, 835-843].
      Insertion of both domains occurs at saturable SecYEGDFyajC sites and is rapidly
      followed by deinsertion. SecA also associates nonsaturably and unproductively
      with lipid. In the presence of ATP, yet without involvement of preprotein or
      SecYEG, lipid-bound SecA forms domains that are protease-resistant and that
      remain so even upon subsequent membrane disruption. Unlike the [35S]SecA that
      inserts into the membrane at SecYEGDFyajC as it promotes preprotein
      translocation, lipid-associated [35S]SecA does not chase from its protease
      resistant state upon the addition of excess SecA. The finding that two domains of
      SecA (which together represent most regions of the polypeptide chain) cycle into
      the membrane during preprotein translocation, as well as the distinction between
      the membrane association of SecA at translocation sites of SecYEGDFyajC and at
      nonproductive lipid sites, are fundamental to the study of the role of SecA in
      preprotein movement.

PMID- 9159116
TI  - Animal fatty acid synthase: functional mapping and cloning and expression of the
      domain I constituent activities.
AB  - Animal fatty acid synthase (FAS; EC 2.3.1.85) is a homodimer of a multifunctional
      subunit protein and catalyzes the synthesis of palmitate from acetyl-CoA, malonyl
      CoA, and NADPH. The subunit (Mr approximately 270,000) carries seven distinct
      component activities and a site for the prosthetic group 4'-phosphopantetheine
      (acyl carrier protein). Based on proteolytic mapping, the organization of the
      activity domains along the subunit polypeptide from the N terminus is as follows:
      beta-ketoacyl synthase, acetyl and malonyl transacylases, beta-hydroxyacyl
      dehydratase, enoyl reductase, beta-ketoacyl reductase, acyl carrier protein, and
      thioesterase. By comparing the amino acid sequences of the chicken, rat, and
      human synthases, we found that kallikrein cleavage sites occur in the least
      conserved regions of the FAS polypeptide subunit. Determining the amino acid
      sequences of the N-terminal end of the major kallikrein cleavage peptides helped
      delineate the most likely boundaries of the component activities in the cDNA
      derived amino acid sequence. To confirm this organization, we cloned the chicken
      FAS cDNA coding for domain I and expressed it in Escherichia coli as a maltose
      binding fusion protein. The isolated recombinant protein contained the activities
      of the acetyl and malonyl transacylases and the beta-hydroxyacyl dehydratase.
      Based on the boundaries of the acetyl and malonyl transacylases and the beta
      hydroxyacyl dehydratase, we also cloned the appropriate cDNA fragments encoding
      the domains that contain the transacylases and the dehydratase in pET vectors and
      expressed them in E. coli as thioredoxin-6xHis fusion proteins. The purified
      recombinant proteins contained, respectively, the activities of the acetyl and
      malonyl transacylases and the dehydratase. These results not only confirmed the
      order of the component activities in domain I, but also paved the way for
      successful expression and characterization of the remaining activities.

PMID- 9159117
TI  - A molecular biology-based approach to resolve the subunit orientation of
      lipoprotein lipase.
AB  - The subunit orientation of a dimeric enzyme influences the mechanism of action
      and function. To determine the subunit arrangement of lipoprotein lipase (LPL), a
      molecular biology-based approach was initiated. An eight amino acid linker region
      was engineered between two LPL monomers and expressed in COS-7 cells. The
      resultant tandem-repeat molecule (LPLTR) was lipolytically active and had kinetic
      parameters, salt inhibition, cofactor-dependent activity, heparin-binding
      characteristics, and a functional unit size very similar to the expressed native
      human enzyme. By these criteria, LPLTR was the functional equivalent of native
      LPL. Considering the length of the linker peptide (no more than 24 A), monomers
      in the tethered molecule were restricted to a head-to-tail subunit arrangement.
      Since LPLTR demonstrated native enzyme-like properties while constrained to this
      subunit arrangement, these results provide the first compelling evidence that
      native LPL monomers are arranged in a head-to-tail subunit orientation within the
      active dimer. Thus, LPL function in physiology, lipolysis, and binding to cell
      surface components must now be addressed with this subunit orientation in mind.
      The utility of the tandem-repeat approach to resolve the subunit arrangement of
      an obligate dimer has been demonstrated with LPL and could be generalized for use
      with other oligomeric enzymes.

PMID- 9159118
TI  - Activation of mitogen-activating protein kinase by glucose is not required for
      insulin secretion.
AB  - In the insulinoma cell line INS-1, a model system for glucose-regulated insulin
      secretion, the mitogen-activating protein (MAP) kinases/extracellular signal
      regulated protein kinases, ERK1 and ERK2 are activated up to 15-fold by
      physiological concentrations of glucose, in the range of 3-12 mM. The related MAP
      kinase family members, the c-Jun-N-terminal kinases/stress-activated protein
      kinases are insensitive to glucose, while the p38 MAP kinase is slightly glucose
      responsive (1.5-fold). ERK activation is dependent on glucose metabolism and the
      subsequent increase in calcium influx. Inhibiting activation of ERK1 and ERK2
      with the MEK1/2 inhibitor PD98059 has no effect on insulin secretion, indicating
      that ERK activity is not necessary for secretion under these conditions. Glucose
      activates ERK1 and ERK2 in cytosolic and purified nuclear fractions of INS-1
      cells and more of each is found in nuclei from glucose-treated cells. These
      findings suggest that some of the glucose-dependent actions of ERKs will be
      exerted in the nucleus.

PMID- 9159119
TI  - BRCA1 is a component of the RNA polymerase II holoenzyme.
AB  - The familial breast-ovarian tumor suppressor gene product BRCA1 was found to be a
      component of the RNA polymerase II holoenzyme by several criteria. BRCA1 was
      found to copurify with the holoenzyme over multiple chromatographic steps. Other
      tested transcription activators that could potentially contact the holoenzyme
      were not stably associated with the holoenzyme as determined by copurification.
      Antibody specific for the holoenzyme component hSRB7 specifically purifies BRCA1.
      Immunopurification of BRCA1 complexes also specifically purifies
      transcriptionally active RNA polymerase II and transcription factors TFIIF,
      TFIIE, and TFIIH. Moreover, a BRCA1 domain, which is deleted in about 90% of
      clinically relevant mutations, participates in binding to the holoenzyme complex
      in cells. These data are consistent with recent data identifying transcription
      activation domains in the BRCA1 protein and link the BRCA1 tumor suppressor
      protein with the transcription process as a holoenzyme-bound protein.

PMID- 9159120
TI  - Cdc6p-dependent loading of Mcm proteins onto pre-replicative chromatin in budding
      yeast.
AB  - The Cdc6 protein is essential for the assembly of pre-replicative complexes (pre
      RCs) at origins of DNA replication in the budding yeast Saccharomyces cerevisiae.
      This reaction is blocked in vivo by the cyclin-dependent kinase Cdc28p, together
      with its regulatory subunits, the B type cyclins that are present throughout S,
      G2, and M phases. Because the destruction of B type cyclins and the consequent
      inactivation of the kinase are essential for exit from mitosis, pre-RC formation
      can only occur after passage through mitosis. Therefore, pre-RC formation has
      been proposed to be essential for coupling S phase and mitosis and for limiting
      DNA replication to once per cell cycle. The Mcm2-7 family of proteins has been
      implicated in limiting replication to once per cell cycle from experiments with
      Xenopus egg extracts. Here we show that the Mcm proteins of budding yeast are
      abundant and are quantitatively found in a chromatin-enriched fraction
      specifically during the G1 phase of the cell cycle. This chromatin binding
      depends on the de novo synthesis of Cdc6p, providing evidence that a conserved
      biochemical pathway plays a critical role in coordinating DNA replication with
      mitosis in both yeast and higher eukaryotes. Cdc6p and the origin recognition
      complex can be selectively removed from this chromatin-enriched fraction without
      removing the Mcm proteins. From these results, we propose that Cdc6p (and the
      origin recognition complex) nucleates the binding of Mcm proteins to chromatin,
      but once bound, the Mcm proteins appear to interact tightly with some other
      component of chromatin.

PMID- 9159121
TI  - Synergy between adjacent zinc fingers in sequence-specific DNA recognition.
AB  - Zif268-like zinc fingers are generally regarded as independent DNA-binding
      modules that each specify three base pairs in adjacent, but discrete, subsites.
      However, crystallographic evidence suggests that a contact also can occur from
      the second helical position of one finger to the subsite of the preceding finger.
      Here we show for the three-finger DNA-binding domain of the protein Zif268, and a
      panel of variants, that deleting the putative contact from finger 3 can affect
      the binding specificity for the 5' base in the adjoining triplet, which forms
      part of the binding site of finger 2. This finding demonstrates that Zif268-like
      zinc fingers can specify overlapping 4-bp subsites, and that sequence specificity
      at the boundary between subsites arises from synergy between adjacent fingers.
      This has important implications for the design and selection of zinc fingers with
      novel DNA binding specificities.

PMID- 9159122
TI  - Diffusion control in an elementary protein folding reaction.
AB  - The cold-shock protein CspB (from Bacillus subtilis), a very small protein of 67
      residues, folds extremely fast in a reversible N &lrharr; U two-state reaction.
      Both unfolding and refolding are strongly decelerated when the viscosity of the
      solvent is increased by adding ethylene glycol or sucrose. The folding of CspB
      thus seems to follow Kramers' model for reactions in which the reactants must
      diffuse together. It indicates that the compaction of the protein chain occurs in
      the rate-limiting step of folding. Chain diffusion to a productively collapsed
      form and the crossing of a high energy barrier are thus tightly coupled in this
      folding reaction, and the measured reaction rate depends on both the diffusion of
      the protein chain in the solvent and the magnitude of the activation energy. We
      suggest that in protein folding an energetic barrier is essential to separate the
      native from the unfolded conformations of a protein. This barrier protects the
      ordered structure of a native protein against continuous unfolding by diffusive
      chain motions and leads to apparent two-state behavior.

PMID- 9159123
TI  - Messenger RNA deadenylylation precedes decapping in mammalian cells.
AB  - In yeast, the major mRNA degradation pathway is initiated by poly(A) tail
      shortening that triggers mRNA decapping. The mRNA is then degraded by 5'-to-3'
      exonucleolysis. In mammalian cells, even though poly(A) tail shortening also
      precedes mRNA degradation, the degradation pathway has not been elucidated. We
      have used a reverse transcription-PCR approach that relies on mRNA
      circularization to measure the poly(A) tail length of four mammalian mRNAs. This
      approach allows for the simultaneous analysis of the 5' and 3' ends of the same
      mRNA molecule. For all four mRNAs analyzed, this strategy permitted us to
      demonstrate the existence of small amounts of decapped mRNA species which have a
      shorter poly(A) tail than their capped counterparts. Kinetic analysis of one of
      these mRNAs indicates that the decapped species with a short poly(A) tail are
      mRNA degradation products. Therefore, our results indicate that decapping is
      preceded by a shortening of the poly(A) tail in mammalian cells, as it is in
      yeast, suggesting that this mRNA degradation pathway is conserved throughout
      eukaryotic evolution.

PMID- 9159124
TI  - Estimation of the DNA sequence discriminatory ability of hairpin-linked
      lexitropsins.
AB  - Three- and four-ring polyamides containing N-methylimidazole and N-methylpyrrole,
      and their hairpin-linked derivatives, bind side-by-side in the minor groove of
      DNA in a sequence-specific manner. The sequences recognized by side-by-side
      molecules are dependent on the pairings of the polyamide rings to the bases. In
      this study we report a mathematical model for estimating the free energies of
      binding for gamma-aminobutyric acid-linked polyamides to 5- and 6-bp DNA
      sequences. The model parameters are calibrated by a least-squares fit to 35
      experimental binding constants. The model performs well in cross-validation
      experiments and the parameters are consistent with previously proposed empirical
      rules of polyamide-DNA binding. We apply the model to the design of targeted
      polyamides, evaluating the ability of the proposed polyamides to bind to a DNA
      sequence of interest while minimizing binding to the remaining DNA sequences.

PMID- 9159125
TI  - The RNA-binding protein, TB-RBP, is the mouse homologue of translin, a
      recombination protein associated with chromosomal translocations.
AB  - The mouse RNA-binding protein, TB-RBP, suppresses translation in vitro and
      attaches mRNAs to microtubules by binding to conserved elements in the 3'
      untranslated regions of specific mRNAs. We have now purified TB-RBP from
      testicular and brain cytoplasmic extracts and cloned its cDNA. We find that the
      mouse TB-RBP cDNAs contain an open reading frame of 228 amino acids with a
      leucine zipper domain within its C terminus, a transmembrane helix, and a group
      of putative phosphorylation sites. TB-RBP shows 99% identity to the human
      protein, translin, a recombination hotspot-binding protein associated with
      chromosomal translocations [Aoki, K., Suzuki, K., Sugano, T., Tasaka, T.,
      Nakahara, K., Kuge, O., Omori, A. & Kasai, M. (1995) Nat. Genet. 10, 167-174]. As
      shown for translin, TB-RBP also binds to single-stranded DNAs containing a broad
      range of consensus sequences, many of which are similar to the Y and H RNA
      binding sequences. Recombinant TB-RBP was synthesized and an antiserum was
      prepared against the recombinant protein. The identity between translin and TB
      RBP was confirmed by demonstrating that immunoprecipitation of TB-RBP from
      testicular extracts abolished formation of the RNA-TB-RBP complex. Based upon its
      DNA binding to target sequences in clustered breakpoint regions, we propose that
      TB-RBP may be involved in DNA recombination or DNA repair in male germ cells.

PMID- 9159126
TI  - Axial rotation of sliding actin filaments revealed by single-fluorophore imaging.
AB  - In the actomyosin motor, myosin slides along an actin filament that has a helical
      structure with a pitch of approximately 72 nm. Whether myosin precisely follows
      this helical track is an unanswered question bearing directly on the motor
      mechanism. Here, axial rotation of actin filaments sliding over myosin molecules
      fixed on a glass surface was visualized through fluorescence polarization imaging
      of individual tetramethylrhodamine fluorophores sparsely bound to the filaments.
      The filaments underwent one revolution per sliding distance of approximately 1
      microm, which is much greater than the 72 nm pitch. Thus, myosin does not "walk"
      on the helical array of actin protomers; rather it "runs," skipping many
      protomers. Possible mechanisms involving sequential interaction of myosin with
      successive actin protomers are ruled out at least for the preparation described
      here in which the actin filaments ran rather slowly compared with other in vitro
      systems. The result also indicates that each "kick" of myosin is primarily along
      the axis of the actin filament. The successful, real-time observation of the
      changes in the orientation of a single fluorophore opens the possibility of
      detecting a conformational change(s) of a single protein molecule at the moment
      it functions.

PMID- 9159127
TI  - Femtosecond time resolution in x-ray diffraction experiments.
AB  - This paper presents the theoretical background for a synthesis of femtosecond
      spectroscopy and x-ray diffraction. When a diffraction quality crystal with 0.1
      0.3 mm overall dimensions is photoactivated by a femtosecond laser pulse
      (physical length = 0.3 microm), the evolution of molecules at separated points in
      the crystal will not be simultaneous because a finite time is required for the
      laser pulse to propagate through the body of the crystal. Utilizing this lack of
      global crystal synchronization, topographic x-ray diffraction may enable
      femtosecond temporal resolution to be achieved from reflection profiles in the
      diffraction pattern with x-ray exposures of picosecond or longer duration. Such x
      ray pulses are currently available, and could be used to study femtosecond
      reaction dynamics at atomic resolution on crystals of both small- and
      macromolecules. A general treatment of excitation and diffraction geometries in
      relation to spatial and temporal resolution is presented.

PMID- 9159129
TI  - Characterization of VPS41, a gene required for vacuolar trafficking and high
      affinity iron transport in yeast.
AB  - Mutations in the yeast gene VPS41 give rise to poor growth on low iron medium,
      severe alterations in vacuolar morphology, and cause the missorting of membranous
      and soluble vacuolar proteins. Our studies predict that VPS41 encodes a
      hydrophilic protein of 992 amino acids that contains no obvious signal sequence
      or hydrophobic domains. The deduced Vps41p sequence contains a domain rich in
      glutamic and aspartic residues, as well as a domain with resemblance to a region
      of clathrin heavy chain. We have also identified and sequenced putative VPS41
      homologues from Caenorhabditis elegans, plants, and humans. The VPS41 homologues
      (but not the yeast VPS41 itself) contain a conserved cysteine-rich RING-H2 zinc
      finger at their COOH termini. Biochemical experiments suggest that VPS41
      functions in post-Golgi protein processing: the deletion mutant exhibits
      defective high affinity transport due to impaired Fet3p activity and also
      exhibits defects in the processing and sorting of multiple vacuolar hydrolases.

PMID- 9159128
TI  - Conditional activation defect of a human Gsalpha mutant.
AB  - Hormonal signals activate trimeric G proteins by promoting exchange of GTP for
      GDP bound to the G protein's alpha subunit (Galpha). Here we describe a point
      mutation that impairs this activation mechanism in the alpha subunit of Gs,
      producing an inherited disorder of hormone responsiveness. Biochemical analysis
      reveals an activation defect that is paradoxically intensified by hormonal and
      other stimuli. By substituting histidine for a conserved arginine residue, the
      mutation removes an internal salt bridge (to a conserved glutamate) that normally
      acts as an intramolecular hasp to maintain tight binding of the gamma-phosphate
      of GTP. In its basal, unperturbed state, the mutant alphas binds guanosine 5'
      [gamma-thio]triphosphate (GTP[gammaS]), a GTP analog, slightly less tightly than
      does normal alphas, but (in the GTP[gammaS]-bound form) can stimulate adenylyl
      cyclase. The activation defect becomes prominent only under conditions that
      destabilize binding of guanine nucleotide (receptor stimulation) or impair the
      ability of alphas to bind the gamma-phosphate of GTP (cholera toxin, AlF4- ion).
      Although GDP release is usually the rate-limiting step in nucleotide exchange,
      the biochemical phenotype of this mutant alphas indicates that efficient G
      protein activation by receptors and other stimuli depends on the ability of
      Galpha to clasp tightly the GTP molecule that enters the binding site.

PMID- 9159130
TI  - Activation of hypoxia-inducible factor 1alpha: posttranscriptional regulation and
      conformational change by recruitment of the Arnt transcription factor.
AB  - In response to hypoxia the hypoxia-inducible factor-1 (HIF-1) mediates
      transcriptional activation of a network of genes encoding erythropoietin,
      vascular endothelial growth factor, and several glycolytic enzymes. HIF-1
      consists of a heterodimer of two basic helix-loop-helix PAS (Per/Arnt/Sim)
      proteins, HIF-1alpha and Arnt. HIF-1alpha and Arnt mRNAs are constitutively
      expressed and were not altered upon exposure of HeLa or HepG2 cells to hypoxia,
      suggesting that the activity of the HIF-1alpha-Arnt complex may be regulated by
      some as yet unknown posttranscriptional mechanism. In support of this model, we
      demonstrate here that Arnt protein levels were not increased under conditions
      that induce an hypoxic response in HeLa and HepG2 cells. However, under identical
      conditions, HIF-1alpha protein levels were rapidly and dramatically up-regulated,
      as assessed by immunoblot analysis. In addition, HIF-1alpha acquired a new
      conformational state upon dimerization with Arnt, rendering HIF-1alpha more
      resistant to proteolytic digestion in vitro. Dimerization as such was not
      sufficient to elicit the conformational change in HIF-1alpha, since truncated
      forms of Arnt that are capable of dimerizing with HIF-1alpha did not induce this
      effect. Moreover, the high affinity DNA binding form of the HIF-1alpha-Arnt
      complex was only generated by forms of Arnt capable of eliciting the allosteric
      change in conformation. In conclusion, the combination of enhanced protein levels
      and allosteric change by dimerization defines a novel mechanism for modulation of
      transcription factor activity.

PMID- 9159131
TI  - Expression of maspin in prostate cells is regulated by a positive ets element and
      a negative hormonal responsive element site recognized by androgen receptor.
AB  - Prostate cancer is the most common cancer in men. The molecular mechanisms
      leading to its development are poorly understood. Maspin is a tumor-suppressing
      serpin expressed in normal breast and prostate epithelium. We have found that
      expression of maspin in normal and carcinoma-derived prostate epithelial cells is
      differentially regulated at the transcriptional level. We have identified two
      different kinds of cis elements, Ets and hormonal responsive element (HRE), in
      the maspin promoter. The Ets element is active in regulating maspin expression in
      normal prostate epithelial cells but inactive in tumor cells. The HRE site is a
      negative element that is active in both cell types. This negative DNA sequence
      can repress a heterologous promoter recognized by the androgen receptor. We
      conclude that expression of maspin is under the influence of both a positive Ets
      and a negative HRE element. Loss of maspin expression during tumor progression
      apparently results from both the absence of transactivation through the Ets
      element and the presence of transcription repression through the negative HRE
      element recognized by androgen receptor.

PMID- 9159132
TI  - The I/LWEQ module: a conserved sequence that signifies F-actin binding in
      functionally diverse proteins from yeast to mammals.
AB  - Talin is an actin-binding protein involved in integrin-mediated cell adhesion and
      spreading. The C-terminal 197 amino acids of vertebrate talin are 45% similar to
      the C-terminal residues of Sla2, a yeast protein implicated in polarized assembly
      of the yeast actin cytoskeleton. Talin is also homologous in this region to
      nematode talin, cellular slime mold filopodin, and an Sla2 homolog from nematode.
      Analysis of the conserved C-terminal sequences of these five proteins with BLOCK
      MAKER reveals a series of four blocks, which we name the I/LWEQ module after the
      conserved initial residues in each block. Experiments presented here show that
      the conserved protein domain represented by the I/LWEQ module competes
      quantitatively with native talin for binding to F-actin in vitro. Furthermore,
      the corresponding domain of Sla2 binds to both yeast and vertebrate F-actin in
      vitro. Mutation of one of the conserved residues in the fourth conserved block
      abolishes the interaction of the Sla2 I/LWEQ module with F-actin. These results
      establish the location of an F-actin binding domain in native talin, demonstrate
      that direct interaction of Sla2 with actin is a possible basis for its effect on
      the actin cytoskeleton in vivo, and define the I/LWEQ consensus as a new actin
      binding motif.

PMID- 9159133
TI  - In situ molecular association of dystrophin with actin revealed by sensitized
      emission immuno-resonance energy transfer.
AB  - A novel method was developed to detect molecular associations of dystrophin with
      actin in cryostat muscle tissue sections by combining resonance energy transfer
      technology with immunohistochemical techniques. This method takes advantage of
      the long phosphorescent lifetime of terbium chelates, a property that enables the
      accurate determination of energy transfer in biological tissues by lifetime
      measurements of sensitized emission. After a brief excitation pulse, terbium
      chelates emit for milliseconds after the intrinsically high autofluorescence of
      biological specimens has decayed to negligible levels. Rat skeletal muscle tissue
      sections were labeled with both anti-dystrophin monoclonal antibody conjugated to
      a terbium-based resonance energy transfer donor and anti-actin
      tetramethylrhodamine phalloidin as an acceptor. Resonance energy transfer between
      the two probes indicated that the distance separating the probes is within 10 nm
      (about the size of an IgG2b antibody molecule). The fraction of antibodies that
      participated in resonance energy transfer was estimated to be 80-90% because of
      the close agreement between the quenching of donor phosphorescence and the
      efficiency of resonance energy transfer revealed by lifetime measurements of
      sensitized emission by tetramethyl-rhodamine phalloidin. Sensitized emission was
      detectable only when both anti-dystrophin antibody and tetramethyl-rhodamine
      phalloidin were present. These results indicate that actin and dystrophin are
      closely associated within the cell. This method is potentially applicable to the
      investigation of many types of intracellular associations.

PMID- 9159134
TI  - Developmental parameters of cell death in the wing disc of Drosophila.
AB  - Apoptotic cell death in wing imaginal discs takes place in single cells or small
      clusters of neighboring cells. These cells are distributed throughout the anlage
      at early stages and in recognizable territories at late larval and pupal stages.
      Apoptotic cells remain in the epithelium 2-4 h, prior to being engulfed in place
      by hemolymph cells. Experimentally induced apoptosis in single cells or
      territories is accompanied by nonautonomous death of adjacent cells and of cells
      further away in adjacent territories. These effects are followed by changes in
      cell proliferation in both territories. Apogenetic mosaics in mutant discs show
      cell death throughout the anlage. Apoptosis provides a mechanism, in addition to
      cell proliferation control, for matching territories with different positional
      values or different genetic specifications.

PMID- 9159135
TI  - Hematopoiesis in the fetal liver is impaired by targeted mutagenesis of a gene
      encoding a non-DNA binding subunit of the transcription factor, polyomavirus
      enhancer binding protein 2/core binding factor.
AB  - The Pebpb2 gene encodes a non-DNA binding subunit of the heterodimeric
      transcription factor, polyomavirus enhancer binding protein 2/core binding factor
      (PEBP2/CBF), and is rearranged in inversion of chromosome 16 associated with
      human acute myeloid leukemia. To investigate its physiological function, Pebpb2
      was mutated by a targeting strategy to generate a null mutant. The homozygous
      mutation in mice proved lethal in embryos around embryonic day 12.5, apparently
      due to massive hemorrhaging in the central nervous system. In addition,
      definitive hematopoiesis in the liver was severely impaired. The observed
      phenotype was indistinguishable from that reported for homozygous disruption of
      AML1, which encodes a DNA binding subunit of PEBP2/CBF. Thus, the results
      indicate that the two subunits function together as a heterodimeric PEBP2/CBF in
      vivo and that PEBP2/CBF plays an essential role in the development of definitive
      hematopoiesis.

PMID- 9159136
TI  - Cooperation of Pax2 and Pax5 in midbrain and cerebellum development.
AB  - Midbrain and cerebellum development depends on an organizing center that is
      located at the midbrain-hindbrain junction of the vertebrate embryo. Expression
      of the two closely related transcription factors Pax2 and Pax5 overlaps spatially
      and temporally in this region of the developing central nervous system. To study
      a possible interaction of these transcription factors in midbrain and cerebellum
      patterning, we have generated Pax5, Krd double mutant mice. The transgene-induced
      Krd mutation corresponds to an approximately 7-centimorgan chromosome 19 deletion
      that eliminates the entire Pax2 locus. The heterozygous Krd mutation deleting one
      Pax2 allele had no effect on midbrain and cerebellum development. Moreover, only
      minor developmental defects were previously observed at the midline of the
      inferior colliculus and anterior cerebellum in mice that were homozygous for a
      targeted Pax5 mutation. Similar morphological alterations were observed in 80% of
      all compound heterozygous Pax5 (+/-) Krd (+/-) mice. However, in the remaining
      20% of compound heterozygotes, the inferior colliculi were missing, and the
      vermis of the cerebellum was severely disrupted due to the failure of the
      cerebellar primordia to fuse at the midline. Inactivation of the second Pax5
      allele in Pax5 (-/-) Krd (+/-) mice resulted in complete loss of the posterior
      midbrain and cerebellum, as the tissue originating from the midbrain-hindbrain
      boundary region was deleted in the embryo as early as day 9.5. On the basis of
      these data, we propose that the cooperation of Pax2 and Pax5 is essential for
      normal functioning of the organizing center at the midbrain-hindbrain junction.

PMID- 9159138
TI  - Safety in numbers: sophisticated vigilance by Allenby's gerbil.
AB  - Since 1963, nonlinear predation theory has predicted that, at low population
      densities, victim species may well be mutualistic rather than competitive. Theory
      identifies this mutualism as a principal source of dynamic instability in the
      interaction. Using gerbils and trained barn owls, we conducted the first (to our
      knowledge) field tests of the theory's prediction of mutualism. The behavior of
      the gerbils confirms its existence.

PMID- 9159137
TI  - The origin and efficient derivation of embryonic stem cells in the mouse.
AB  - By explanting tissues isolated microsurgically from implanting strain 129 mouse
      blastocysts individually on STO feeder cells we have established that embryonic
      stem (ES) cells originate from the epiblast (primitive ectoderm). Isolated early
      epiblasts yielded ES cell lines at a substantially higher frequency than intact
      blastocysts regardless of whether they were explanted whole or as strictly single
      cell suspensions. When explanted from delayed-implanting 129 blastocysts,
      epiblasts gave lines consistently in 100% of cases. If primary embryonic
      fibroblasts rather than STO cells were used as feeders, germline-competent ES
      cell lines were obtained readily from epiblasts of delayed-implanting blastocysts
      of several hitherto refractory strains, particularly when recombinant leukemia
      inhibitory factor was included in the medium during the initial period of
      culture. Because lines were obtained from the nonpermissive CBA/Ca strain at a
      rate of up to 56%, this approach to the derivation of germline-competent ES cell
      lines may not only prove generic for the mouse but also worth pursuing in other
      species of mammal.

PMID- 9159139
TI  - Old World fruitbat phylogeny: evidence for convergent evolution and an endemic
      African clade.
AB  - Knud Andersen (1912, Catalogue of the Chiroptera in the Collections of the
      British Museum: I. Megachiroptera, British Museum of Natural History, London)
      divided Old World fruitbats (family Pteropodidae) into the rousettine,
      cynopterine, epomophorine, eonycterine, and notopterine sections. The latter two
      sections comprise the subfamily Macroglossinae; members of this subfamily exhibit
      specializations for nectarivory (e.g., elongated, protrusible, brushy tongues)
      and cluster together in cladistic analyses based on anatomical characters. Other
      evidence, including single-copy DNA hybridization, suggests that macroglossines
      are either paraphyletic or polyphyletic; this implies that adaptations for pollen
      and nectar feeding evolved independently in different macroglossine lineages or
      were lost in nonmacroglossines after evolving in a more basal common ancestor.
      Hybridization data also contradict Andersen's phylogeny in providing support for
      an endemic African clade that includes representatives of three of Andersen's
      sections. Here, we present complete mitochondrial 12S rRNA and valine tRNA gene
      sequences for 20 pteropodids, including representatives of all of Andersen's
      sections, and examine the aforementioned controversies. Maximum likelihood,
      minimum evolution, and maximum parsimony analyses all contradict macroglossine
      monophyly and provide support for an African clade that associates Megaloglossus
      and Lissonycteris and those two with Epomophorus. In conjunction with the DNA
      hybridization results, there are now independent lines of molecular evidence
      suggesting: (i) convergent evolution of specializations for nectarivory, at least
      in Megaloglossus versus other macroglossines, and (ii) a previously unrecognized
      clade of endemic Africa taxa. Estimates of divergence time based on 12S rRNA and
      DNA hybridization data are also in good agreement and suggest that extant
      fruitbats trace back to a common ancestor 25 million to 36 million years ago.

PMID- 9159141
TI  - BCL8, a novel gene involved in translocations affecting band 15q11-13 in diffuse
      large-cell lymphoma.
AB  - Translocations affecting the chromosomal region 15q11-13 and various other
      partners are recurrent in diffuse large-cell lymphomas (DLCL). To identify the
      putative gene, here named BCL8, involved in these translocations we have cloned
      the breakpoint region from a DLCL patient with t(14;15)(q32;q11-13) and the
      corresponding germ-line region from chromosome 15. The genomic locus on
      chromosome 15 is clonally rearranged in about 4% of DLCL in agreement with the
      frequency of 15q11-13 translocations. A probe derived from the BCL8 locus on
      chromosome 15 detected a transcript in human testis and prostate, whereas no
      expression was found in spleen, thymus, and blood leukocytes. Analysis of the
      BCL8 cDNA clones isolated from human testis cDNA library showed that the BCL8
      gene generates a major transcript of 2.6 kb and a less prominent 4.5-kb species
      due to differential polyadenylylation. By reverse transcription-PCR analysis of
      RNA extracted from frozen DLCL samples and lymphoma cell lines, BCL8 expression
      was detected in all patients carrying 15q11-13 abnormalities and in a fraction of
      randomly selected DLCL patients. These results suggest that the BCL8 gene is not
      normally expressed in lymphoid tissues, but its expression can be activated by
      chromosomal translocation or by other mechanisms in DLCL. Ectopic expression of
      BCL8 in a significant proportion of DLCL suggests an important role for this gene
      in the molecular pathogenesis of B cell lymphoma.

PMID- 9159140
TI  - Molecular evolution of angiosperm mitochondrial introns and exons.
AB  - Numbers of substitutions per site for 15 protein-coding genes and six introns of
      the plant mitochondria were estimated to compare modes and tempos of evolution
      between exons and introns, and numbers of insertions-deletions per site also were
      investigated in introns. Intra-gene homogeneity of numbers of substitutions per
      site was assessed further among different taxa and between mitochondrial and
      nuclear paralogs translocated from the mitochondrial genome. Gene-to-gene
      differences in numbers of substitutions per site were found to be higher for
      nonsynonymous than synonymous sites, and this could be due to differential
      selection if mutation rate is assumed constant for the genome. Some mitochondrial
      genes have evolved as fast as chloroplast genes, thus faster than previously
      thought. For coxI, relative rate tests showed that woody taxa evolved slower than
      annuals at synonymous sites. Generation time, population size, and speciation
      rate are likely factors involved in this rate heterogeneity. Introns were less
      constrained than their adjacent exons for both overall numbers of substitutions
      per site and indels, but, on average, overall numbers of substitutions per site
      for introns were similar to numbers of synonymous substitutions per site for
      exons. Correlations were generally high between numbers of substitutions and
      numbers of indels per site for the same intron. Mitochondrial genes transferred
      to the nucleus had an accelerated rate of substitution per site, which was most
      significant at synonymous sites. These differences between paralogs in two
      different genomes are likely the result of different mutation rates.

PMID- 9159142
TI  - SOS factors involved in translesion synthesis.
AB  - Mutations are permanent DNA sequence changes that can be induced when replication
      occurs on a damaged DNA template. In Escherichia coli, the process of translesion
      synthesis past a lesion that hinders replication requires the induction of SOS
      controlled gene products, among which are those of the umuDC operon. To study
      translesion synthesis in vivo, we have constructed single-stranded vectors
      containing single 2-acetylaminofluorene adducts located within -1 and -2
      frameshift mutation hot spots formed by short repetitive sequences. These adducts
      strongly hinder DNA replication as only 2-5% of the molecules give rise to
      progeny under non-SOS-induced conditions. Induction of the SOS response lead to a
      10-fold increase in survival. Adducts present within repetitive sequences trigger
      the formation of misaligned primer/template replication intermediates which, upon
      elongation, will result in the fixation of frameshift errors (mutagenic
      translesion synthesis). Surprisingly we find that elongation from the nonslipped
      intermediate depends upon functional umuDC+ gene products, whereas elongation
      from the slipped intermediate is umuDC+ independent but requires another, as yet
      biochemically uncharacterized, SOS function. These data are discussed in terms of
      the different steps involved during translesion synthesis through a replication
      blocking lesion.

PMID- 9159143
TI  - Independent signals regulate development of primary and secondary follicle
      structure in spleen and mesenteric lymph node.
AB  - Lymphotoxin-alpha-deficient (LT-alpha-/-) mice manifest congenital absence of
      lymph nodes (LNs) and Peyer's patches and disturbed spleen follicle structure.
      The splenic white pulp areas show loss of discrete T and B lymphocyte zones, of
      follicular dendritic cell (FDC) clusters, and of germinal centers (GCs). Tumor
      necrosis factor receptor I-deficient (TNFR-I-/-) mice show similar absence of FDC
      clusters and GCs but retain segregation of T and B cell zones. Rarely are
      mesenteric LNs found in LT-alpha-/- mice. These mesenteric LNs show segregation
      of T and B cell zones similar to wild-type mice. In contrast, mesenteric LNs in
      TNFR-I-/- mice manifest grossly disturbed organization of T and B cells. Both LT
      alpha-/- and TNFR-I-/- mice lacked FDC clusters in LNs and spleen. Interestingly,
      although both LT-alpha-/- and TNFR-I-/- mice that had been immunized with sheep
      red blood cells failed to form GCs in the spleen, they both developed GC-like
      clusters of peanut agglutinin-positive (PNA+) cells in their LNs. Furthermore,
      when lethally irradiated recombination activating gene (RAG)-1-deficient (RAG-1(
      /-)) mice that had received spleen cells from LT-alpha-/- mice were immunized
      with sheep red blood cells, they failed to generate PNA+ clusters in the
      reconstituted spleen but showed robust PNA+ clusters in the reconstituted LNs.
      These data demonstrate that the signals that regulate the development of distinct
      T and B cell zones as well as the signals that regulate B cell activation to
      produce clusters of PNA+ cells differ between the spleen and LNs.

PMID- 9159144
TI  - Characterization of the major histocompatibility complex class II binding site on
      LAG-3 protein.
AB  - The lymphocyte activation gene-3 (LAG-3), selectively transcribed in human
      activated T and NK cells, encodes a ligand for major histocompatibility complex
      (MHC) class II molecules. Like CD4, LAG-3 ectodomain is composed of four Ig-like
      domains (D1-D4). Nothing is known about the LAG-3 regions or residues required to
      form a stable MHC class II binding site. In contrast to CD4, soluble LAG-3
      molecules stably interact with MHC class II molecules expressed on the cell
      surface. In addition, the first two N-terminal domains of soluble LAG-3 (D1 and
      D2) molecules, alone, are capable of binding MHC class II. From a LAG-3 model
      structure, we designed mutants and tested their ability to bind MHC class II
      molecules in an intercellular adhesion assay. We found residues on the membrane
      distal, CDR1-2-containing top face of D1 that are essential for either binding or
      repulsing MHC class II proteins. Most of these residues are clustered at the base
      of a large extra-loop structure that is a hallmark of the LAG-3 D1 Ig-like
      domain. In addition, as for CD4, oligomerization of LAG-3 on the cell surface may
      be required to form a stable MHC binding site because mutation of three residues
      in the ABED beta-strands containing side of D1 results in a dominant negative
      effect (i.e., binding inhibition of coexpressed wild-type LAG-3).

PMID- 9159145
TI  - Radiation and stress-induced apoptosis: a role for Fas/Fas ligand interactions.
AB  - The lpr gene encodes a defective form of Fas, a cell surface protein that
      mediates apoptosis. This defect blocks apoptotic deletion of autoreactive T and B
      cells, leading to lymphoproliferation and lupus-like autoantibody production. The
      effects of the lpr Fas mutation on other kinds of physiologically relevant
      apoptosis are largely undocumented. To assess whether some of the apoptosis known
      to occur after ionizing radiation might be mediated by Fas/Fas ligand (FasL)
      interactions, we quantitated in vitro apoptosis by flow cytometry measurement of
      DNA content in splenic T and B cells from irradiated 5- to 8-month-old B6/lpr
      mice. Total apoptosis of both lpr and control cells was substantial after
      treatment; however there was a significant difference between B6 (73%) and lpr
      (25%) lymphocyte apoptosis. Thy1, CD4, CD8, and IgM cells from lpr showed much
      lower levels of apoptosis than control cells after irradiation. Apoptosis induced
      by heat shock was also impaired in lpr. The finding that gamma-irradiation
      increased Fas expression on B6 cells and that irradiation-induced apoptosis could
      be blocked with a Fas-Fc fusion protein further supported the possible
      involvement of Fas in this form of apoptosis. Fas/FasL interactions may thus play
      an important role in identifying and eliminating damaged cells after gamma
      irradiation and other forms of injury.

PMID- 9159146
TI  - A lymphocyte-activating monoclonal antibody induces regression of human tumors in
      severe combined immunodeficient mice.
AB  - Monoclonal antibodies were raised against Daudi B-lymphoblastoid cell line
      membranes. An mAb (BAT) was selected for its ability to stimulate human and
      murine lymphocyte proliferation. BAT induced cytotoxicity in human and murine
      lymphocytes against natural killer cell-sensitive and -resistant tumor cell
      lines. A single intravenous administration of BAT to mice that had been
      inoculated with various murine tumors (e.g., B16 melanoma, 3LL carcinoma, and
      methylcholanthrene fibrosarcoma) resulted in striking antitumor effects as
      manifested by complete tumor regression and prolonged survival of the treated
      mice. BAT exhibited a diminished but significant antitumor effect in athymic nude
      mice, which are deficient in T lymphocytes, and in beige mice, which are
      deficient in NK cells. Furthermore, selective depletion of T or NK cells in mice
      reduced the response to the antitumor effect of BAT. These data indicate a dual
      role for T and NK cells in mediating the antitumor activity of BAT. We report
      here on the antitumor activity of BAT mAb on human tumor xenografts in mice. BAT
      demonstrated an antitumor effect in nude mice bearing human colon carcinoma
      (HT29) xenografts. It failed, however, to inhibit established lung metastases in
      severe combined immunodeficient (SCID) mice that had been inoculated (i.v.) with
      SK28 human melanoma. Engraftment of human lymphocytes into SCID mice bearing
      human melanoma xenografts rendered them responsive to the antitumor effect of
      BAT. The efficacy of BAT in the regression of human tumors by activation of human
      lymphocytes indicates its potential clinical use.

PMID- 9159147
TI  - The T cell receptor repertoire of intestinal intraepithelial gammadelta T
      lymphocytes is influenced by genes linked to the major histocompatibility complex
      and to the T cell receptor loci.
AB  - Most of the gammadelta T cells in the intestinal epithelium of normal mice use
      the Vgamma1 or the Vgamma7 gene segments. However, the relative proportions of
      gammadelta intraepithelial lymphocytes expressing either the Vgamma1 or the
      Vgamma7 chain vary among different strains of mice whereas they are quite
      constant between different individuals of the same strain, suggesting that
      genetic factors, rather than environmental factors, are responsible for the
      observed differences. To analyze the genetic factors influencing the
      representation of different gammadelta T cell subsets in the intestinal
      epithelium, we used available anti-T cell antigen receptor (TCR) V region
      specific mAbs against Vgamma1, Vgamma4, Vgamma7, and Vdelta4 to examine the TCR
      repertoire of intraepithelial gammadelta lymphocytes in a set of (C57BL/6 x
      DBA/2) recombinant inbred strains. Our results show that the representation of
      different Vgamma and Vdelta gene products among gammadelta intestinal
      intraepithelial lymphocytes is under a complex genetic control with a marked
      influence by genes closely linked to the TCRgamma, TCRdelta, and major
      histocompatibility complex loci.

PMID- 9159148
TI  - Elevated levels of cysteine protease activity in saliva and salivary glands of
      the nonobese diabetic (NOD) mouse model for Sjogren syndrome.
AB  - Nonobese diabetic (NOD) mice develop an anti-exocrine gland pathology similar to
      human Sjogren syndrome. Recently, we demonstrated that NOD-scid mice develop
      severe loss of submandibular acinar cells with concomitant appearance of abnormal
      isoforms of salivary proteins suggesting de novo enzymatic cleavage. Because
      these changes may indicate activation of apoptotic proteases, we examined saliva
      and salivary tissue for cysteine protease activity. Cysteine protease activities
      were elevated in saliva and gland lysates from 20-week-old NOD and NOD-scid mice
      as compared with age- and sex-matched BALB/c or 8-week-old NOD mice. This
      activity appeared in the submandibular glands, but not in the parotid glands.
      Western blot analyses using antibodies directed against specific apoptotic
      proteases (interleukin 1beta converting enzyme, Nedd-2, and Apopain/CPP 32)
      confirmed these findings. Submandibular glands from NOD-scid mice exhibited the
      greatest increase in proteolytic activity, indicating that infiltrating
      leukocytes are not responsible for these changes. Western blot analyses also
      failed to reveal changes in the levels of cystatins (saliva proteins that inhibit
      protease activity). Thus, increased cysteine protease activity appears to be
      directly related to submandibular acinar cell loss in NOD-scid mice involving the
      apoptotic pathway. Additional protease activity in saliva and gland lysates of
      older NOD and NOD-scid mice, apparently mutually distinct from cysteine
      proteases, generated an enzymatically cleaved parotid secretory protein. We
      suggest, therefore, that proteolytic enzyme activity contributes to loss of
      exocrine gland tolerance by generating abnormally processed protein constituents.

PMID- 9159149
TI  - In the absence of the invariant chain, HLA-DR molecules display a distinct array
      of peptides which is influenced by the presence or absence of HLA-DM.
AB  - The independent influences of invariant chain (Ii) and HLA-DM molecules on the
      array of naturally processed peptides displayed by HLA-DR molecules were studied
      using transfected cell lines. The absence of Ii led to an altered set of HLA-DR
      bound peptides as judged by the discriminating responses of alloreactive T cell
      clones. While most T cell clones raised against DR+Ii+DM+ peripheral blood
      mononuclear cells (PBMC) failed to respond to DR+Ii-DM- cells, T cell clones
      raised against DR+Ii-DM- transfectants were not stimulated by DR+Ii+DM+ cells.
      Furthermore, coexpression of HLA-DM with HLA-DR1 in the absence of Ii augmented
      responses of anti-PBMC T cell clones but inhibited allorecognition by T cell
      clones raised against DR+Ii-DM- transfectants. The conformational integrity of
      the class II molecules, as judged by serology, suggests that the patterns of
      reactivity of the T cell clones reflect specificity for different alloantigen
      bound peptides. Hence, discordant regulation of expression of major
      histocompatibility complex class II, Ii, and HLA-DM molecules in vivo may lead to
      the display of novel self-peptides and possible interruption of self-tolerance.

PMID- 9159151
TI  - Antigens produced in plants by infection with chimeric plant viruses immunize
      against rabies virus and HIV-1.
AB  - The coat protein (CP) of alfalfa mosaic virus was used as a carrier molecule to
      express antigenic peptides from rabies virus and HIV. The antigens were
      separately cloned into the reading frame of alfalfa mosaic virus CP and placed
      under the control of the subgenomic promoter of tobacco mosaic virus CP in the
      30BRz vector. The in vitro transcripts of recombinant virus with sequences
      encoding the antigenic peptides were synthesized from DNA constructs and used to
      inoculate tobacco plants. The plant-produced protein (virus particles) was
      purified and used for immunization of mice. Both antigens elicited specific virus
      neutralizing antibodies in immunized mice.

PMID- 9159150
TI  - Differential ability of T cell subsets to undergo activation-induced cell death.
AB  - Human T cell clones were analyzed for their susceptibility to activation-induced
      cell death (AICD) in response to CD3/T cell receptor ligation. AICD was observed
      only in Th1 clones and was Fas-mediated, whereas Th2 clones resisted AICD.
      Analysis of a panel of Th0 clones, characterized by their ability to secrete both
      Th1 and Th2 cytokines, revealed that this subset included both AICD-sensitive
      (type A) and -resistant (type B) clones. Resistance to AICD by Th2 and Th0-type B
      clones was not due to lack of expression of either Fas receptor or its ligand.
      Paradoxically, the AICD-resistant clones were susceptible to apoptosis when Fas
      receptor was directly ligated by anti-Fas antibodies. However, prior activation
      of the resistant clones by monoclonal antibodies to CD3/TCR complex induced
      resistance against Fas-mediated apoptosis. Thus, the Fas-FasL pathway is critical
      for the induction of AICD in T cells, and moreover this pathway can be negatively
      regulated in the AICD-resistant clones by signals that are generated from
      ligation of the CD3/TCR complex.

PMID- 9159152
TI  - Major histocompatibility complex gene mapping in the amphibian Xenopus implies a
      primordial organization.
AB  - One of the most provocative recent discoveries in immunology was the description
      of a genetic linkage in the major histocompatibility complex (MHC) between
      structurally unrelated genes whose products are involved in processing and
      presentation of antigens for recognition by T lymphocytes. Genes encoding MHC
      class I molecules, which bind and present at the cell surface proteolytic
      fragments of cytosolic proteins, are linked to nonhomologous genes whose products
      are involved in the production and subsequent transfer of such fragments into the
      endoplasmic reticulum. In mammals, the class I presentation and processing genes
      are found in different regions of the MHC. To examine the evolutionary origins of
      this genetic association, linkage studies were carried out with Xenopus, an
      amphibian last sharing an ancestor with mammals over 350 million years ago. In
      contrast to mammals, the single copy Xenopus class I gene is located between the
      class II and III regions, speculated to be in close linkage with the processing
      and transport genes. In addition to suggesting a primordial organization of genes
      involved in class I antigen presentation, these linkage studies further provide
      insight into the origins of the MHC class III region and the phenomenon of class
      I gene instability in the mammalian MHC.

PMID- 9159153
TI  - Resource competition as a mechanism for B cell homeostasis.
AB  - Cellular competition for survival signals offers a cogent and appealing mechanism
      for the maintenance of cellular homeostasis [Raff, M. C. (1992) Nature (London)
      356, 397-400]. We present a theoretical and experimental investigation of the
      role of competition for resources in the regulation of peripheral B cell numbers.
      We use formal ecological competition theory, mathematical models of interspecific
      competition, and competitive repopulation experiments to show that B cells must
      compete to persist in the periphery and that antigen forms a part of the
      resources over which B cells compete.

PMID- 9159155
TI  - Stable gene transfer and expression of human blood coagulation factor IX after
      intramuscular injection of recombinant adeno-associated virus.
AB  - We sought to determine whether intramuscular injection of a recombinant adeno
      associated virus (rAAV) vector expressing human factor IX (hF.IX) could direct
      expression of therapeutic levels of the transgene in experimental animals. High
      titer (10(12)-10(13) vector genomes/ml) rAAV expressing hF.IX was prepared,
      purified, and injected into hindlimb muscles of C57BL/6 mice and Rag 1 mice. In
      the immunocompetent C57BL/6 mice, immunofluorescence staining of muscle harvested
      3 months after injection demonstrated the presence of hF.IX protein, and PCR
      analysis of muscle DNA was positive for AAV DNA, but no hF.IX was detected in
      mouse plasma. Further studies showed that these mice had developed circulating
      antibodies to hF.IX. In follow-up experiments in Rag 1 mice, which carry a
      mutation in the recombinase activating gene-1 and thus lack functional B and T
      cells, similar results were seen on DNA analysis of muscle, but these mice also
      demonstrated therapeutic levels (200-350 ng/ml) of F. IX in the plasma. The time
      course of F.IX expression demonstrates that levels gradually increase over a
      period of several weeks before reaching a plateau that is stable 6 months after
      injection. In other experiments we demonstrate colocalization of hF.IX and
      collagen IV in intersitial spaces between muscle fibers. Collagen IV has recently
      been identified as a F.IX-binding protein; this finding explains the unusual
      pattern of immunofluorescent staining for F.IX shown in these experiments. Thus
      rAAV can be used to direct stable expression of therapeutic levels of F.IX after
      intramuscular injection and is a feasible strategy for treatment of patients with
      hemophilia B.

PMID- 9159154
TI  - Reactivation of silenced, virally transduced genes by inhibitors of histone
      deacetylase.
AB  - Retroviral and adeno-associated viral sequences can dramatically silence
      transgene expression in mice. We now report that this repression also occurs in
      stably infected HeLa cells when the cells are grown without selection. Expression
      of a transduced lacZ gene (rAAV/CMVlacZ) is silenced in greater than 90% of cells
      after 60 days in culture. Surprisingly, high-level expression can be reactivated
      by treating the cells with sodium butyrate or trichostatin A but not with 5
      azacytidine. When cell clones with integrated copies of rAAV/CMVlacZ were
      isolated, lacZ expression was silenced in 80% of the clones; however, lacZ
      expression was reactivated in all of the silenced clones by treatment with
      butyrate or trichostatin A. The two drugs also reactivated a silenced globin gene
      construct (rAAV/HS2alphabetaAS3) in stably infected K562 cells. Trichostatin A is
      a specific inhibitor of histone deacetylase; therefore, we propose that
      hyperacetylation of histones after drug treatment changes the structure of
      chromatin on integrated viral sequences and relieves repression of transduced
      genes. The reactivation of silenced, transduced genes has implications for gene
      therapy. Efficient viral gene transfer followed by drug treatment to relieve
      suppression may provide a powerful combination for treatment of various genetic
      and infectious diseases.

PMID- 9159156
TI  - Growth hormone-releasing hormone antagonist MZ-4-71 inhibits in vivo
      proliferation of Caki-I renal adenocarcinoma.
AB  - In view of evidence that growth hormone (GH) and insulin-like growth factors
      (IGF) may play a role in the development of renal cell carcinoma (RCC), we
      investigated the effects of growth hormone-releasing hormone (GH-RH) antagonist
      MZ-4-71 on the proliferation of the human renal adenocarcinoma cell line Caki-I
      in vitro and in vivo. Male nude mice bearing xenografts of human Caki-I RCC were
      treated for 4 weeks with MZ-4-71 injected s.c. twice daily at a dose of 20 microg
      per animal. Tumor growth, serum, liver, and tumor IGF levels and IGF-I receptor
      concentrations in Caki-I cell membranes were measured. After 4 weeks of therapy,
      the final volume of Caki-I tumors in nude mice treated with MZ-4-71 was
      significantly (P < 0.01) decreased to 52.6 +/- 12.3 mm3 as compared with controls
      that measured 504.2 +/- 104.1 mm3. Treatment with GH-RH antagonist also
      significantly reduced tumor weight, serum levels of GH and IGF-I, liver
      concentrations of IGF-I, and tumor levels of IGF-I and IGF-II. High-affinity
      binding sites for IGF-I were detected in the cell membranes of Caki-I tumors. IGF
      I and IGF-II stimulated the proliferation of Caki-I cells in tissue cultures.
      Antagonist MZ-4-71 could inhibit in vitro growth of Caki-I cells, but only at
      high concentrations. Our findings demonstrate that GH-RH antagonist MZ-4-71 can
      significantly inhibit the growth of Caki-I RCC. MZ-4-71 may exert its suppressive
      effect on tumor growth through a reduction in GH release from the pituitary and
      the subsequent decrease in the production of IGF-I in the liver and IGF-I and II
      by the tumors. The efficacy of MZ-4-71 suggests that this compound could be
      considered for the therapy of recurrent or metastatic RCC.

PMID- 9159157
TI  - Keratinocyte expression of the type 2 interleukin 1 receptor mediates local and
      specific inhibition of interleukin 1-mediated inflammation.
AB  - Epidermal keratinocytes can express two types of interleukin 1 (IL-1) receptors:
      IL-1R1, which is active in signal transduction, and the less well characterized
      IL-1R2, which is incapable of transducing a signal and can be shed from cells.
      The binding of IL-1 in solution by IL-1R2 has been demonstrated, and it has been
      proposed to inhibit IL-1-mediated responses through this mechanism. We and others
      have reported that keratinocytes can be induced to express IL-1R2 both in vitro
      and in vivo, often under conditions that also favor IL-1 gene expression. We
      hypothesized that production of IL-1R2 by keratinocytes would be an efficient
      means to achieve local inhibition of IL-1-mediated responses without systemic
      consequences. To test this hypothesis, we have generated transgenic mice that
      constitutively express IL-1R2 on basal keratinocytes. Keratinocytes cultured from
      these animals shed the soluble form of the receptor into culture supernatants,
      and IL-1-inducible production of granulocyte/macrophage colony-stimulating factor
      was markedly inhibited. In vivo, acute cutaneous vascular leakage, as well as
      chronic inflammation induced by a well characterized IL-1-dependent stimulus, was
      significantly inhibited in IL-1R2 transgenic animals. In contrast, contact
      hypersensitivity was unaffected, suggesting that overexpression of IL-1R2 did not
      inhibit all types of inflammation globally. Finally, systemic injection of IL-1
      induced equivalent levels of plasma IL-6 in IL-1R2 transgenic and nontransgenic
      mice, suggesting that the activity of the transgenic IL-1R2 remained
      predominantly local and did not influence systemic IL-1 responses. We conclude
      that tissue-specific production of IL-1R2 can mediate IL-1 antagonism in tissue
      microenvironments without systemic consequences. Our transgenic mice may be a
      useful tool for determining the degree to which different types of cutaneous
      inflammation depend on the IL-1 system.

PMID- 9159158
TI  - Human BRCA1 inhibits growth in yeast: potential use in diagnostic testing.
AB  - Germline-inactivating mutations of BRCA1 result in a hereditary predisposition to
      breast and ovarian cancer. Truncating mutations of BRCA1 predispose to cancer and
      can be ascertained by protein truncation testing or sequencing. However, cancer
      predisposing missense mutations of BRCA1 are difficult to distinguish from
      polymorphisms by genetic testing methods currently used. Here we show that
      expression of BRCA1 or BRCA1 fused to a GAL4 activation domain in Saccharomyces
      cerevesiae inhibits growth, resulting in small colonies easily distinguishable
      from vector-transformed controls. The growth inhibitory effect can be localized
      to sequences encoding the recently described BRCA1 C-terminal domains. Growth
      suppression by a BRCA1 fusion protein is not influenced by introduction of
      neutral polymorphisms but is diminished or abolished by frameshift, nonsense, or
      disease-associated missense mutations located in the C-terminal 305 amino acids
      of BRCA1. These observations may permit the functional significance of many BRCA1
      sequence changes to be assessed in yeast. Additionally, the correlation of growth
      suppression with wild-type forms of BRCA1 suggests that the assay may be capable
      of detecting functionally conserved interactions between the evolutionarily
      conserved BRCA1 C-terminal domains and cellular elements found in both human and
      yeast cells.

PMID- 9159159
TI  - Blocking activator protein-1 activity, but not activating retinoic acid response
      element, is required for the antitumor promotion effect of retinoic acid.
AB  - Retinoic acid is one of the most promising drugs for chemotherapy and
      chemoprevention of cancer. Either blocking activator protein-1 (AP-1) activity or
      activating retinoic acid response element (RARE) have been proposed to be
      responsible for its antitumor activity. However, evidence for this hypothesis is
      lacking in vivo studies. To address this issue, we used an AP-1-luciferase
      transgenic mouse as a carcinogenesis model and new synthetic retinoids that are
      either selective inhibitors of AP-1 activation or selective activators of the
      RARE. The results showed that the SR11302, an AP-1 inhibition-specific retinoid,
      and other AP-1 inhibitors such as trans-retinoic acid and fluocinolone acetonide,
      markedly inhibit both 12-O-tetradecanoylphorbol-13-acetate-induced papilloma
      formation and AP-1 activation in 7,12-dimethyl benz(a)anthracene-initiated mouse
      skin (P < 0.05). In contrast, repeated applications of SR11235, a retinoid with
      RARE transactivating activity, but devoid of AP-1 inhibiting effect, did not
      cause significant inhibition of papilloma formation and AP-1 activation (P >
      0.05). These results provide the first in vivo evidence that the antitumor effect
      of retinoids is mediated by blocking AP-1 activity, but not by activation of
      RARE.

PMID- 9159160
TI  - Positionally cloned human disease genes: patterns of evolutionary conservation
      and functional motifs.
AB  - Positional cloning has already produced the sequences of more than 70 human genes
      associated with specific diseases. In addition to their medical importance, these
      genes are of interest as a set of human genes isolated solely on the basis of the
      phenotypic effect of the respective mutations. We analyzed the protein sequences
      encoded by the positionally cloned disease genes using an iterative strategy
      combining several sensitive computer methods. Comparisons to complete sequence
      databases and to separate databases of nematode, yeast, and bacterial proteins
      showed that for most of the disease gene products, statistically significant
      sequence similarities are detectable in each of the model organisms. Only the
      nematode genome encodes apparent orthologs with conserved domain architecture for
      the majority of the disease genes. In yeast and bacterial homologs, domain
      organization is typically not conserved, and sequence similarity is limited to
      individual domains. Generally, human genes complement mutations only in
      orthologous yeast genes. Most of the positionally cloned genes encode large
      proteins with several globular and nonglobular domains, the functions of some or
      all of which are not known. We detected conserved domains and motifs not
      described previously in a number of proteins encoded by disease genes and
      predicted functions for some of them. These predictions include an ATP-binding
      domain in the product of hereditary nonpolyposis colon cancer gene (a MutL
      homolog), which is conserved in the HS90 family of chaperone proteins, type II
      DNA topoisomerases, and histidine kinases, and a nuclease domain homologous to
      bacterial RNase D and the 3'-5' exonuclease domain of DNA polymerase I in the
      Werner syndrome gene product.

PMID- 9159162
TI  - Apoptin induces apoptosis in human transformed and malignant cells but not in
      normal cells.
AB  - The chicken anemia virus protein apoptin induces a p53-independent, Bcl-2
      insensitive type of apoptosis in various human tumor cells. Here, we show that,
      in vitro, apoptin fails to induce programmed cell death in normal lymphoid,
      dermal, epidermal, endothelial, and smooth-muscle cells. However, when normal
      cells are transformed they become susceptible to apoptosis by apoptin. Long-term
      expression of apoptin in normal human fibroblasts revealed that apoptin has no
      toxic or transforming activity in these cells. In normal cells, apoptin was found
      predominantly in the cytoplasm, whereas in transformed and malignant cells it was
      located in the nucleus, suggesting that the localization of apoptin is related to
      its activity. These properties make apoptin a potential agent for the treatment
      of a large number of tumors, also those lacking p53 and/or overexpressing Bcl-2.

PMID- 9159161
TI  - Amphotropic murine leukemia viruses induce spongiform encephalomyelopathy.
AB  - Recombinants of amphotropic murine leukemia virus (A-MuLV) have found widespread
      use in retroviral vector systems due to their ability to efficiently and stably
      infect cells of several different species, including human. Previous work has
      shown that replication-competent recombinants containing the amphotropic env
      gene, encoding the major SU envelope glycoprotein that determines host tropism,
      induce lymphomas in vivo. We show here that these viruses also induce a
      spongiform encephalomyelopathy in mice inoculated perinatally. This fatal central
      nervous system disease is characterized by noninflammatory spongiform lesions of
      nerve and glial cells and their processes, and is associated with moderate astro-
      and microgliosis. The first clinical symptoms are ataxia, tremor, and spasticity,
      progressing to complete tetraparesis and incontinence, and finally death of the
      animal. Sequences within the amphotropic env gene are necessary for disease
      induction. Coinfection of A-MuLV recombinants with nonneuropathogenic ecotropic
      or polytropic MuLV drastically increases the incidence, degree, and distribution
      of the neurodegenerative disorder. The consequence of these results in view of
      the use of A-MuLV recombinants in the clinic is discussed.

PMID- 9159163
TI  - Localized gene action controlling intestinal neoplasia in mice.
AB  - Mice heterozygous for the ApcMin (Min) mutation develop adenomas throughout the
      intestinal tract. Apc is believed to be involved in cell migration, adhesion, and
      polarity. Adenoma multiplicity and growth rate are modulated by an unlinked
      modifier locus, Mom1. The secretory phospholipase Pla2g2a is a candidate for
      Mom1. Here, we investigate the range of action of Apc and Mom1. Analysis of
      chimeric Min mice indicates that the actions of both Apc and Mom1 are localized
      within the cell lineage that gives rise to intestinal tumors.

PMID- 9159164
TI  - Suppression of insulin-like growth factor type I receptor by a triple-helix
      strategy inhibits IGF-I transcription and tumorigenic potential of rat C6
      glioblastoma cells.
AB  - Homopurine (AG) and homopyrimidine (CT) oligodeoxyribonucleotides predicted to
      form triple-helical (triplex) structures have been shown to specifically suppress
      gene expression when supplied to cultured cells. Here we present evidence that
      homopurine RNA (effector) sequences designed to form a triplex with a homopurine.
      homopyrimidine sequence 3' to the termination codon of the insulin-like growth
      factor type I receptor (IGF-IR) structural gene can efficiently suppress IGF-IR
      gene transcription. Transfection vectors were constructed to drive transcription
      of either AG or CT variant triplex-forming strands. To increase the probability
      of obtaining stable transfectants with adequate expression of effector sequences,
      these were designed to be transcribed together with cDNA sequences conferring
      neomycin resistance as a fusion transcript. Rat C6 glioblastoma cells transfected
      with the AG variant showed dramatic reduction of IGF-IR transcripts compared with
      untransfected cells. The AG transfectants also exhibited marked down-regulation
      of the IGF-I, and an enhanced accumulation of serine protease inhibitor nexin-I
      mRNA. Similar changes in gene expression were observed following transfection of
      C6 cells with constructs transcribing antisense RNA to IGF-IR transcripts, but
      were not observed in C6 cells transfected with either the CT triplex variant or
      with vector lacking triplex-forming sequences. Moreover, C6 cells transfected
      with AG triplex variant displayed a dramatic inhibition of tumor growth when
      injected into nude mice. The results suggest that a triple-helix strategy can be
      used to inhibit transcription elongation of the IGF-IR gene, and emphasize the
      efficacy of triplex-mediated gene inhibition in an animal model.

PMID- 9159165
TI  - Fas ligand deficiency in HIV disease.
AB  - Apoptosis is postulated to be involved as an anti-viral immune mechanism by
      killing infected cells before viral replication has occurred. The Fas-Fas ligand
      interaction is a powerful regulator of T cell apoptosis and could potentially act
      as a potent anti-viral immune mechanism against T cell tropic virus such as human
      immunodeficiency virus (HIV). We investigated the status of Fas ligand in
      peripheral blood mononuclear cells (PBMCs) obtained from persons infected with
      HIV. We found that monocytes in freshly isolated PBMCs from healthy individuals
      possess cell surface Fas ligand. In contrast, monocytes in freshly isolated PBMCs
      from HIV-infected patients had no detectable Fas ligand on the cell surface.
      Consistent with these findings of surface expression, Fas ligand activity was
      deficient in the cells from HIV-infected persons. The effect of replacing Fas
      ligand activity on HIV production by patients' cells was assessed in an in vitro
      assay. The addition of a functional anti-Fas antibody to PBMCs from HIV-infected
      individuals inhibited viral production by greater than 90% without affecting
      lymphocytic function. These findings suggest the possibility of a new therapeutic
      modality for the treatment of HIV-infected individuals based on the
      reconstitution of Fas ligand activity.

PMID- 9159166
TI  - Homodimerization of the human interleukin 4 receptor alpha chain induces Cepsilon
      germline transcripts in B cells in the absence of the interleukin 2 receptor
      gamma chain.
AB  - The cytokines interleukin (IL)-4 and IL-13 play a critical role in inducing
      Cepsilon germline transcripts and IgE isotype switching in human B cells. The IL
      4 receptor (IL-4R) in B cells is composed of two chains, the IL-4-binding IL
      4Ralpha chain, which is shared with the IL-13R, and the IL-2Rgamma (gammac)
      chain, which is shared with IL-7R, IL-9R, and IL-15R. IL-4 induces Cepsilon
      germline transcripts and IgE isotype switching in B cells from patients with
      gammac chain deficiency. Induction of Cepsilon germline transcripts by IL-4 in B
      cells that lack the gammac chain may involve signaling via the IL-13R.
      Alternatively, the IL-4Ralpha chain may transduce intracellular signals that lead
      to Cepsilon gene transcription independently of its association with other
      chains. We show that ligand-induced homodimerization of chimeric surface
      receptors consisting of the extracellular and transmembrane domains of the
      erythropoietin receptor and of the intracellular domain of IL-4Ralpha induces
      Janus kinase 1 (Jak1) activation, STAT6 activation, and Cepsilon germline
      transcripts in human B cell line BJAB. Disruption of the Jak1-binding proline
      rich Box1 region of IL-4Ralpha abolished signaling by this chimeric receptor.
      Furthermore, B cells transfected with a chimeric CD8alpha/IL-4Ralpha receptor,
      which is expressed on the cell surface as a homodimer, constitutively expressed
      Cepsilon germline transcripts. These results suggest that homodimerization of the
      IL-4Ralpha chain is sufficient to transduce Jak1-dependent intracellular signals
      that lead to IgE isotype switching.

PMID- 9159167
TI  - Effect of estrogen upon cyclic ADP ribose metabolism: beta-estradiol stimulates
      ADP ribosyl cyclase in rat uterus.
AB  - Cyclic ADP ribose (cADPR) has been shown to trigger Ca2+ release from
      intracellular stores through ryanodine receptor/channel. In our previous study we
      observed that all-trans-retinoic acid stimulates cADPR synthesis by ADP ribose
      cyclase (ADPR cyclase) in cultured epithelial cells. We have now investigated
      whether cADPR may play a signaling role in action of beta-estradiol (E2), an
      archetypal steroid superfamily hormone, upon its major target organ, uterus, in
      vivo. Administration of E2 to gonadectomized rats (0.2 mg/kg per day for 7 days)
      resulted in an approximately Delta + 300% increase of ADPR cyclase activity in
      extracts from uterus, but in liver, brain, or skeletal muscle ADPR cyclase was
      unchanged. Most of the E2-stimulated uterine ADPR cyclase was associated with
      membranes. The higher ADPR cyclase activity in response to E2 was due to the
      increase of VMAX without change in Km. Simultaneous administration of estrogen
      antagonist tamoxifen (8 mg/kg per day) with E2 (0.2 mg/kg per day) prevented an
      increase in ADPR cyclase. In uterine extracts from E2-treated rats, the rate of
      cADPR inactivation by cADPR hydrolase and the activity of NADase was increased,
      but to a much lesser degree than activity of ADPR cyclase. Our results indicate
      that E2, via action to its nuclear receptors in vivo, increases ADPR cyclase
      activity in uterus. We propose that some of the estrogen effects, and by
      extension the effects of other steroid superfamily hormones, upon specialized
      cellular functions and upon hormone-induced gene expression in target cells, are
      mediated by cADPR-Ca2+ release pathway.

PMID- 9159168
TI  - Loss of functional cell surface transforming growth factor beta (TGF-beta) type 1
      receptor correlates with insensitivity to TGF-beta in chronic lymphocytic
      leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in
      Western countries, and there is significant variability in survival within CLL
      clinical stages. Earlier studies showed that CLL cells produce and are usually
      growth inhibited by transforming growth factor beta type 1 (TGF-beta1),
      suggesting a mechanism for the clinically indolent course of most CLL. Here we
      studied the mechanism by which CLL cells from about one-third of the patients are
      insensitive to TGF-beta1. Of the 13 patients studied, CLL cells isolated from the
      peripheral blood of 8 patients were sensitive to growth inhibition by TGF-beta1,
      as determined by incorporation of tritiated thymidine, whereas those from 5
      patients were completely resistant to TGF-beta1. As judged by binding of
      radiolabeled TGF-beta1 followed by cross-linking and immunoprecipitation with
      anti-receptor antisera, CLL cells sensitive to TGF-beta1 exhibited normal cell
      surface expression of both types 1 and 2 TGF-beta receptors. In contrast, all CLL
      cells resistant to TGF-beta1 exhibited no detectable surface type I receptors
      able to bind TGF-beta1, but normal expression of type II receptors. Both TGF
      beta1-sensitive and TGF-beta1-resistant CLL cells contained normal amounts of
      both type 1 and type 2 receptor mRNAs. Specific loss of type 1 receptor
      expression represents a new mechanism by which cells acquire resistance to TGF
      beta1-mediated growth inhibition in the development and progression of human
      lymphoproliferative malignancies.

PMID- 9159169
TI  - The second finger of Urbs1 is required for iron-mediated repression of sid1 in
      Ustilago maydis.
AB  - The urbs1 gene encodes a transcriptional regulator of siderophore biosynthesis in
      Ustilago maydis. Biological and DNA-binding activities of the two putative zinc
      finger motifs of Urbs1 were studied by analyzing mutants containing altered
      finger domains. The mutated urbs1 alleles from three previously described N'
      methyl-N'-nitro-N-nitrosoguanidine (NTG) mutants were mapped and cloned by a gap
      repair procedure. Sequence analyses revealed single amino acid substitutions in
      two of the NTG mutants. Both mutations (G-507 to D in urbs1-1 and P-491 to L in
      urbs1-3), which are located in the Urbs1 C-terminal finger domain, reduced DNA
      binding activity by 10-fold and were sufficient to confer a urbs1-minus
      phenotype. The third NTG urbs1 mutant (urbs1-2) also contained a mutation in one
      of the conserved amino acids (P-518 to S) in the C-terminal finger domain, but
      this mutation alone was not sufficient to confer a urbs1-minus phenotype. A
      second frame shift mutation was identified in urbs1-2 and is necessary for the
      urbs1-minus phenotype. In an analysis of the function of the N-terminal finger of
      Urbs1, the conserved amino acid Arg-350 was mutated to leucine. A Urbs1 protein
      with this mutation complemented a urbs1 null mutant strain. By contrast, a
      similar mutation in the C-terminal domain abolished the ability of Urbs1 to
      regulate siderophore biosynthesis and greatly reduced its ability to bind target
      DNA.

PMID- 9159170
TI  - Long-term potentiation involves increases in the probability of neurotransmitter
      release.
AB  - There is great interest in understanding the mechanisms of expression underlying
      long-term potentiation (LTP). They are agreed to involve an increase in synaptic
      efficacy, which is described by three multiplicative parameters: p, the
      probability of neurotransmitter release; n, the number of active release sites;
      and q, the postsynaptic unit response to transmitter release. We report three new
      lines of evidence suggesting that increases in p contribute to LTP expression.
      (i) When the contributions to LTP by p, n, and q are maximized, and p alone is
      decreased, another high-frequency stimulation elicits additional LTP. The
      additional potentiation is only associated with decreases in paired-pulse
      facilitation (PPF) suggesting an increase in p. (ii) There is an inverse
      relationship between baseline p [corrected] and the magnitude of LTP elicited,
      consistent with p [corrected] having more or less room to increase when p is
      smaller or greater. (iii) It has been shown that there is an inverse relationship
      between the magnitude of LTP induced and the associated changes in PPF. Now I
      find that decreasing p before inducing LTP moves the set-point for measuring
      those changes in PPF from before to after p is decreased, which would only occur
      if p contributes to LTP. Three lines of evidence, then, suggest that increases in
      p contribute to LTP expression, which is consistent with a presynaptic
      contribution to LTP. These experiments do not address potential postsynaptic
      contributions.

PMID- 9159171
TI  - Calmodulin regulation of light adaptation and store-operated dark current in
      Drosophila photoreceptors.
AB  - Phototransduction in Drosophila occurs through inositol lipid signaling that
      results in Ca2+ mobilization. In this system, we investigate the hitherto unknown
      physiological roles of calmodulin (CaM) in light adaptation and in regulation of
      the inward current that is brought about by depletion of cellular Ca2+ stores. To
      see the effects of a decreased Ca-CaM content in photoreceptor cells, we used
      several methods. Transgenic Drosophila P[ninaCDeltaB] flies, which have CaM
      deficient photoreceptors, were studied. The peptide inhibitor M5, which binds to
      Ca-CaM and prevents its action, was applied. A Ca2+-free medium, which prevents
      Ca2+ influx and thereby diminishes the generation of Ca-CaM, was used. The
      decrease in the Ca-CaM level caused the following effects. (i) Fluorescence of
      Ca2+ indicator revealed an enhanced light-induced Ca2+ release from internal
      stores. (ii) Measurements of the light-induced current in P[ninaCDeltaB] cells
      showed a reduced light adaptation. (iii) Internal dialysis of M5 initially
      enhanced excitation and subsequently disrupted the light-induced current. (iv) An
      inward dark current appeared after depletion of the Ca2+ stores with ryanodine
      and caffeine. Importantly, application of Ca-CaM into the photoreceptor cells
      prevented all of the above effects. We propose that negative feedback of Ca-CaM
      on Ca2+ release from ryanodine-sensitive stores mediates light adaptation, is
      essential for light excitation, and keeps the store-operated inward current under
      a tight control.

PMID- 9159172
TI  - Early divergence of magnocellular and parvocellular functional subsystems in the
      embryonic primate visual system.
AB  - In both human and Old World primates visual information is conveyed by two
      parallel pathways: the magnocellular (M) and parvocellular (P) streams that
      project to separate layers of the lateral geniculate nucleus and are involved
      primarily in motion and color/form discrimination. The present study provides
      evidence that retinal ganglion cells in the macaque monkey embryo diverge into M
      and P subtypes soon after their last mitotic division and that optic axons
      project directly and selectively to either the M or P moieties of the developing
      lateral geniculate nucleus. Thus, initial M projections from the eyes overlap
      only in prospective layers 1 and 2, whereas initial P projections overlap within
      prospective layers 3-6. We suggest that the divergence of the M and P pathways
      requires developmental mechanisms different from those underlying competition
      driven segregation of initially intermixed eye-specific domains in the primate
      visual system.

PMID- 9159173
TI  - The neuron-restrictive silencer element: a dual enhancer/silencer crucial for
      patterned expression of a nicotinic receptor gene in the brain.
AB  - The neuron-restrictive silencer element (NRSE) has been identified in several
      neuronal genes and confers neuron specificity by silencing transcription in
      nonneuronal cells. NRSE is present in the promoter of the neuronal nicotinic
      acetylcholine receptor beta2-subunit gene that determines its neuron-specific
      expression in the nervous system. Using transgenic mice, we show that NRSE may
      either silence or enhance transcription depending on the cellular context within
      the nervous system. In vitro in neuronal cells, NRSE activates transcription of
      synthetic promoters when located downstream in the 5' untranslated region, or at
      less than 50 bp upstream from the TATA box, but switches to a silencer when
      located further upstream. In contrast, in nonneuronal cells NRSE always functions
      as a silencer. Antisense RNA inhibition shows that the NRSE-binding protein REST
      contributes to the activation of transcription in neuronal cells.

PMID- 9159174
TI  - Identification of chemical synapses in the pharynx of Caenorhabditis elegans.
AB  - The rhythmic contraction of the Caenorhabditis elegans pharynx is unique in that
      the network of 12 neurons, including two M3 neurons, that regulate the
      contraction is known. The neurotransmitters secreted by these cells, and the
      target cells responding to these chemical signals, are not known. Here, we
      describe an approach to obtain this missing information and use the M3 cells as
      an example. Electrical recordings (electropharyngeograms) were used in
      conjunction with temporally and spatially defined application of
      neurotransmitters via photolysis of inactive, photolabile precursors. To
      illustrate the technique we used pharyngeal preparations in which the two M3
      neurons are intact and preparations in which they were removed by laser
      irradiation. Removal of M3 neurons results in the loss of the small negative
      peaks in the electropharyngeograms and an increase in time during which the
      pharynx remains contracted. We demonstrate that the application of glutamate by
      photolysis of caged glutamate to a pharynx from which the two M3 neurons were
      removed produces effects similar to those observed before removal of the M3
      neurons. In control experiments, photolytic release from photolabile precursors
      of carbamoylcholine, a stable and well characterized analog of acetylcholine, or
      of gamma-aminobutyric acid, from photolabile precursors did not have this effect.
      The response depended on the amount of glutamate released. By reducing the size
      of the photolytic beam, glutamate was released at several different locations of
      the pharynx. Two areas of the pharynx mainly respond to the application of
      glutamate; one corresponds to the pm4 muscle cells in the metacorpus, and the
      other to the junction between muscle cells pm5 in the isthmus and pm6 in the
      terminal bulb.

PMID- 9159175
TI  - Neurotrophin regulation of ionic currents and cell size depends on cell context.
AB  - Trk receptor activation by neurotrophins is often considered to have a defined
      set of actions on target neurons, including supporting neuronal survival,
      inducing morphological differentiation, and regulating a host of target genes
      that specify neuronal phenotype. It is not known if all such regulatory effects
      are obligatory, or if some may vary depending on the cell context in which the
      receptors are expressed. We have examined this issue by comparing neurotrophin
      effects on the regulation of electrical excitability and morphological
      differentiation in two strains of PC12 cells. We found that while neurotrophins
      induced neurite extension and increased calcium currents in both PC12 cell types,
      sodium current levels were regulated in only one of these strains. Moreover, we
      found little correlation between calcium current levels and the extent of
      morphological differentiation when compared in individual cells of a single
      strain. Thus, the regulatory effects of neurotrophins on cell phenotype are not
      fully determined by the Trk receptors that they activate; rather, they can vary
      with differences in cell context that arise not only between different cell
      lineages, but also between individual cells of clonal relation.

PMID- 9159176
TI  - Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D
      aspartate receptor.
AB  - Severely elevated levels of total homocysteine (approximately millimolar) in the
      blood typify the childhood disease homocystinuria, whereas modest levels (tens of
      micromolar) are commonly found in adults who are at increased risk for vascular
      disease and stroke. Activation of the coagulation system and adverse effects of
      homocysteine on the endothelium and vessel wall are believed to underlie disease
      pathogenesis. Here we show that homocysteine acts as an agonist at the glutamate
      binding site of the N-methyl-D-aspartate receptor, but also as a partial
      antagonist of the glycine coagonist site. With physiological levels of glycine,
      neurotoxic concentrations of homocysteine are on the order of millimolar.
      However, under pathological conditions in which glycine levels in the nervous
      system are elevated, such as stroke and head trauma, homocysteine's neurotoxic
      (agonist) attributes at 10-100 microM levels outweigh its neuroprotective
      (antagonist) activity. Under these conditions neuronal damage derives from
      excessive Ca2+ influx and reactive oxygen generation. Accordingly, homocysteine
      neurotoxicity through overstimulation of N-methyl-D-aspartate receptors may
      contribute to the pathogenesis of both homocystinuria and modest
      hyperhomocysteinemia.

PMID- 9159177
TI  - Selective enhancement of emotional, but not motor, learning in monoamine oxidase
      A-deficient mice.
AB  - Mice deficient in monoamine oxidase A (MAOA), an enzyme that metabolizes
      monoamines such as norepinephrine and serotonin, have elevated norepinephrine and
      serotonin levels in the frontal cortex, hippocampus, and cerebellum, compared
      with normal wild-type mice. Since monoamines in these areas are critically
      involved in a variety of behaviors, we examined learning and memory (using
      emotional and motor tasks) in MAOA mutant mice. The MAOA-deficient mice exhibited
      significantly enhanced classical fear conditioning (freezing to both tone and
      contextual stimuli) and step-down inhibitory avoidance learning. In contrast,
      eyeblink conditioning was normal in these mutant mice. The female MAOA-deficient
      mice also displayed normal species-typical maternal behaviors (nesting, nursing,
      and pup retrieval). These results suggest that chronic elevations of monoamines,
      due to a deletion of the gene encoding MAOA, lead to selective alterations in
      emotional behavior.

PMID- 9159178
TI  - Neuregulins stimulate the functional expression of Ca2+-activated K+ channels in
      developing chicken parasympathetic neurons.
AB  - The developmental expression of macroscopic Ca2+-activated K+ currents (IK[Ca])
      in chicken ciliary ganglion (CG) neurons is dependent in part on trophic factors
      released from preganglionic nerve terminals. Neuregulins are expressed in the
      preganglionic neurons that innervate the chicken CG and are therefore plausible
      candidates for this activity. Application of 1 nM beta1-neuregulin peptide for 12
      hr evokes a large (7- to 10-fold) increase in IK[Ca] in embryonic day 9 CG
      neurons, even in the presence of a translational inhibitor. A similar
      posttranslational effect is produced by high concentrations (10 nM) of epidermal
      growth factor and type alpha transforming growth factor but not by 10 nM alpha2
      neuregulin peptide or by neurotrophins at 40 ng.ml-1. beta1-neuregulin treatment
      for 12 hr also confers Ca2+ sensitivity onto large-conductance (285 pS) K+
      channels observed in inside-out patches. beta-Neuregulins have no effect on
      voltage-activated Ca2+ currents of CG neurons. These data support the hypothesis
      that beta-neuregulins mediate the trophic effects of preganglionic nerve
      terminals on the electrophysiological differentiation of developing CG neurons.

PMID- 9159179
TI  - Serotonin and aggressive motivation in crustaceans: altering the decision to
      retreat.
AB  - In crustaceans, as in most animal species, the amine serotonin has been suggested
      to serve important roles in aggression. Here we show that injection of serotonin
      into the hemolymph of subordinate, freely moving animals results in a renewed
      willingness of these animals to engage the dominants in further agonistic
      encounters. By multivariate statistical analysis, we demonstrate that this
      reversal results principally from a reduction in the likelihood of retreat and an
      increase in the duration of fighting. Serotonin infusion does not alter other
      aspects of fighting behavior, including which animal initiates an encounter, how
      quickly fighting escalates, or which animal eventually retreats. Preliminary
      studies suggest that serotonin uptake plays an important role in this behavioral
      reversal.

PMID- 9159180
TI  - Na,K-ATPase subunit isoforms in human reticulocytes: evidence from reverse
      transcription-PCR for the presence of alpha1, alpha3, beta2, beta3, and gamma.
AB  - The objective of this study has been to determine which Na,K-ATPase isoforms are
      expressed in red blood cells and whether kinetic differences in the uncoupled
      sodium efflux mode between the human red blood cell Na,K-ATPase and other
      preparations can be explained by differences in the underlying subunit
      composition. To this end, human reticulocyte RNA was isolated, reverse
      transcribed, amplified by PCR and appropriate primers, and sequenced. Primers
      from highly conserved areas as well as isoform-specific primers were used. The
      alpha1 and alpha3 isoforms of the alpha subunit, and the beta2 and beta3 isoforms
      of the beta subunit were found. The complete coding regions of the cDNAs for the
      reticulocyte subunits were sequenced from overlapping PCR fragments. No
      difference was found between the reticulocyte isoforms and the ones already
      known. The fact that we found beta2 but not beta1 in reticulocyte single-stranded
      cDNA, and beta1 but not beta2 in a leukocyte library indicates that leukocyte
      contamination of our reticulocyte preparation was negligible. Analysis of a human
      bone marrow library showed that alpha1, alpha2, and alpha3 as well as all three
      beta isoforms were present. The extent to which the kinetic properties of
      uncoupled sodium efflux might depend on different isoform combinations is not yet
      known.

PMID- 9159181
TI  - Novel isoforms of the beta and gamma subunits of the Xenopus epithelial Na
      channel provide information about the amiloride binding site and extracellular
      sodium sensing.
AB  - We have previously identified three homologous subunits alpha, beta, and gamma of
      the highly selective amiloride-sensitive Na channel from the Xenopus laevis
      kidney A6 cell line, which forms a tight epithelium in culture. We report here
      two novel genes, termed beta2 and gamma2, which share 90 and 92% sequence
      identity with the previously characterized beta and gamma XENaC, respectively.
      beta2 and gamma2 transcripts were detected in lung, kidney, and A6 cells grown on
      porous substrate. The physiological and pharmacological profile of the Na channel
      expressed after alphabeta2gamma XENaC cRNA injection in Xenopus oocyte did not
      differ from alphabetagamma XENaC. By contrast, the channel expressed after
      alphabetagamma2 injection showed: (i) a lower maximal amiloride-sensitive sodium
      current, (ii) a higher apparent affinity for external sodium and inactivation of
      the sodium current by high sodium concentrations, and (iii) a lower apparent
      affinity for amiloride (KI alphabetagamma2; 1.34 microM versus alphabetagamma
      0.35 microM). These data indicate that the gamma (and/or gamma2) subunit
      participates in amiloride binding and the sensing of the extracellular sodium
      concentration. The close homology between gamma and gamma2 will help to define
      the domains involved in sensing external sodium and in the structure of this
      important drug receptor.

PMID- 9159182
TI  - Expression of a divergent expansin gene is fruit-specific and ripening-regulated.
AB  - Expansins are proteins that induce extension in isolated plant cell walls in
      vitro and have been proposed to disrupt noncovalent interactions between
      hemicellulose and cellulose microfibrils. Because the plant primary cell wall
      acts as a constraint to cell enlargement, this process may be integral to plant
      cell expansion, and studies of expansins have focused on their role in growth. We
      report the identification of an expansin (LeExp1) from tomato that exhibits high
      levels of mRNA abundance and is specifically expressed in ripening fruit, a
      developmental period when growth has ceased but when selective disassembly of
      cell wall components is pronounced. cDNAs closely related to LeExp1 were also
      identified in ripening melons and strawberries, suggesting that they are a common
      feature of fruit undergoing rapid softening. Furthermore, the sequence of LeExp1
      and its homologs from other ripening fruit define a subclass of expansin genes.
      Expression of LeExp1 is regulated by ethylene, a hormone known to coordinate and
      induce ripening in many species. LeExp1 is differentially expressed in the
      ripening-impaired tomato mutants Nr, rin, and nor, and mRNA abundance appears to
      be influenced directly by ethylene and by a developmentally modulated
      transduction pathway. The identification of a ripening-regulated expansin gene in
      tomato and other fruit suggests that, in addition to their role in facilitating
      the expansion of plant cells, expansins may also contribute to cell wall
      disassembly in nongrowing tissues, possibly by enhancing the accessibility of
      noncovalently bound polymers to endogenous enzymic action.

PMID- 9159183
TI  - Arabidopsis thaliana ethylene-responsive element binding protein (AtEBP), an
      ethylene-inducible, GCC box DNA-binding protein interacts with an ocs element
      binding protein.
AB  - Ocs elements are a group of promoter sequences required for the expression of
      both pathogen genes in infected plants and plant defense genes. Genes for ocs
      element binding factors (OBFs), belonging to a specific class of basic-region
      leucine zipper (bZIP) transcription factors, have been isolated in a number of
      plants. Using protein-protein interaction screening with OBF4 we have isolated
      AtEBP, an Arabidopsis protein that contains a novel DNA-binding domain, the
      AP2/EREBP domain. One class of proteins that contain this domain are the tobacco
      ethylene-responsive element binding proteins (EREBPs). The EREBPs bind the GCC
      box that confers ethylene responsiveness to a number of pathogenesis related (PR)
      gene promoters. AtEBP expression is inducible by exogenous ethylene in wild-type
      plants and AtEBP transcripts are increased in the ctr1-1 mutant, where ethylene
      regulated pathways are constitutively active. Electrophoretic mobility-shift
      assay and DNase I footprint analysis revealed that AtEBP can specifically bind to
      the GCC box. Interestingly, the highest level of AtEBP expression was detected in
      callus tissue, where ocs elements are very active. Synergistic effects of the GCC
      box with ocs elements or the related G-box sequence have been previously
      observed, for example, in the ethylene-induced expression of a PR gene promoter.
      Our results suggest that cross-coupling between EREBP and bZIP transcription
      factors occurs and may therefore be important in regulating gene expression
      during the plant defense response.

PMID- 9159184
TI  - Complete nucleotide sequence of the chloroplast genome from the green alga
      Chlorella vulgaris: the existence of genes possibly involved in chloroplast
      division.
AB  - The complete nucleotide sequence of the chloroplast genome (150,613 bp) from the
      unicellular green alga Chlorella vulgaris C-27 has been determined. The genome
      contains no large inverted repeat and has one copy of rRNA gene cluster
      consisting of 16S, 23S, and 5S rRNA genes. It contains 31 tRNA genes, of which
      the tRNALeu(GAG) gene has not been found in land plant chloroplast DNAs analyzed
      so far. Sixty-nine protein genes and eight ORFs conserved with those found in
      land plant chloroplasts have also been found. The most striking is the existence
      of two adjacent genes homologous to bacterial genes involved in cell division,
      minD and minE, which are arranged in the same order in Escherichia coli. This
      finding suggests that the mechanism of chloroplast division is similar to
      bacterial division. Other than minD and minE homologues, genes encoding ribosomal
      proteins L5, L12, L19, and S9 (rpl5, rpl12, rpl19, and rps9); a chlorophyll
      biosynthesis Mg chelating subunit (chlI); and elongation factor EF-Tu (tufA),
      which have not been reported from land plant chloroplast DNAs, are present in
      this genome. However, many of the new chloroplast genes recently found in red and
      brown algae have not been found in C. vulgaris. Furthermore, this algal species
      possesses two long ORFs related to ycf1 and ycf2 that are exclusively found in
      land plants. These observations suggest that C. vulgaris is closer to land plants
      than to red and brown algae.

PMID- 9159185
TI  - Event-related brain potential correlates of two states of conscious awareness in
      memory.
AB  - We report an event-related potential (ERP) experiment of human recognition memory
      that explored the relation between conscious awareness and electrophysiological
      activity of the brain. We recorded ERPs from healthy adults while they made
      "remember" and "know" recognition judgments about previously seen words. These
      two kinds of judgments reflect "autonoetic" and "noetic" awareness, respectively.
      The ERP effects differed between the two kinds of awareness while they were
      similar for "true" and "false" recognition. Noetic awareness was associated with
      a temporoparietal positivity in the N400 range (325-600 ms) and a late (600-1,000
      ms) frontocentral negativity, whereas autonoetic awareness was associated with a
      widespread, late, bifrontal and left parietotemporal (600-1000 ms) positivity. In
      the very late (1,300-1, 900 ms) time window, a right frontal positivity was
      observed for both remember and know judgments of both true and false targets.
      These results provide physiological evidence for two types of conscious awareness
      in episodic memory retrieval.

PMID- 9159186
TI  - Transgenic approaches for the reduction of Galalpha(1,3)Gal for
      xenotransplantation.
AB  - The major barrier to clinically successful xenotransplantation is the lack of
      effective therapies aimed at eliminating antibody and complement -dependent
      hyperacute rejection. This review examines transgenic strategies to eliminate or
      reduce expression of the major pig to human xenoantigen Galalpha(1,3)Gal such
      that the epitope is no longer recognized by natural human antibodies, by the use
      of glycosidases and/or glycosyltransferases that can competitively and
      effectively inhibit the activity of the alpha1,3galactosyltransferase gene and
      thereby eliminate the xenoantigen Galalpha(1,3)Gal.

PMID- 9159187
TI  - HSP90--news from the front.
AB  - The 90 kDa heat shock protein Hsp90 is a highly conserved and very abundant
      protein in the cytosol of both eukaryotic and prokaryotic cells. The main focus
      in the recent years has been concerned Hsp90's interaction with untransformed
      steroid receptors and newly synthesized kinases. Within these heterocomplexes,
      Hsp90 acts in concert with several other heat shock and non heat shock proteins
      to mediate important regulatory effects. These roles of Hsp90 leave unexplained
      its high abundance and heat shock regulation. More recently, however, Hsp90 has
      been identified as an ATP independent molecular chaperone, which binds
      transiently to folding intermediates in vitro, prevents aggregation and supports
      the refolding of the intermediates to the native state. The finding that Hsp90
      interacts with late, probably highly structured, folding intermediates led to the
      suggestion that Hsp90 might function as a general chaperone for well structured
      not yet native polypeptides. This explanation provides the missing link between
      Hsp90 on the one hand as a highly specialized binding protein and Hsp90 on the
      other hand as a rather promiscuous molecular chaperone.

PMID- 9159188
TI  - MR imaging analysis of heterogeneous leiomyomas of the uterus.
AB  - Thirty-six leiomyomas from the same number of patients that were heterogeneous on
      MR imaging were evaluated for analyzing their MR patterns and for differentiating
      each type of secondary changes by means of MR imaging-pathologic correlation. The
      tumors with a mean diameter of 9 cm could be classified into 4 patterns depending
      on the morphological appearance of signal intensity: speckled (n = 14); nodular
      (n = 11); cystic (n = 9); or indeterminate (n = 2). Speckled pattern was
      associated with a mild degree of hyaline or myxoid degeneration or focal
      necrosis. Nodular pattern was caused by necrosis or cellular leiomyoma, and
      cystic pattern was related to severe hyaline or myxoid degeneration or necrosis.
      Each type of secondary changes within leiomyomas showed distinctive MR findings,
      if they were severely involved. However, use of an additional contrast-enhanced
      study was necessary in some instances for further clarification. MR imaging has a
      potential in distinguishing each type of secondary changes that occur in
      leiomyomas. Various degenerative changes occur in approximately 65% of uterine
      leiomyomas, and are caused mainly by alteration in the blood supply originating
      from rapid growth, pregnancy, mechanical accident, and postmenopausal atrophy.
      These changes include hyaline, mucoid, or myxoid degeneration, calcification,
      cystic changes, necrosis (red degeneration), and fatty metamorphosis. It is well
      known that the presence of degenerative changes within leiomyomas can be
      predicted on MR imaging by a heterogeneous signal intensity on T2-weighted
      images, although clear distinction of each type of degeneration can not be made
      by this modality. Recently, cellular leiomyoma, one of the variants of
      leiomyomas, was also reported to cause heterogeneous signal intensity. However,
      because various other uterine tumors can also have similar signal intensity on MR
      imaging, further evaluation for the heterogeneous leiomyomas appears to be
      necessary. The purpose of our study was to analyze the patterns of heterogeneous
      leiomyomas and to differentiate each type of secondary changes by means of MR
      imaging-pathologic correlation.

PMID- 9159189
TI  - Differential displaying of mRNAs from the atrioventricular region of developing
      chicken hearts at stages 15 and 21.
AB  - In an effort to isolate novel genes that may be involved in the development of
      the cardiac cushions and then the formation of cardiac valves and septa, we
      utilized the differential mRNA display method in conjunction with the whole-mount
      in situ hybridization. The total RNAs used to differentially display were
      prepared from atrioventricular (AV) canal regions of stage 15 and stage 21
      chicken hearts because critical events known to be important for the AV valve and
      septum formation occur during this period of the development. We have
      successfully obtained 14 potential candidate genes. Three examples, 15H16
      (phospholamban), E13 (skeletal alpha-tropomyosin) and 21C (a novel gene), are
      discussed here. Levels of mRNA expression in developing hearts were determined by
      Northern blot analysis and their expression patterns were revealed and compared
      using whole-mount in situ hybridization. Both phospholamban and skeletal alpha
      tropomyosin messages in the myocardium of the AV canal region showed significant
      decrease during this period of the development. The 21C differential display
      product detects a novel 9.5 Kb message whose expression is cardiac-specific at
      early stages of development. The expression level of the 21C gene appeared to be
      increased from stage 15 to stages 21 and 25 as determined by both Northern blot
      analysis and in situ hybridization. From these data, we demonstrate that the
      differential display method together with the whole-mount in situ hybridization
      could be an effective means for the isolation of novel and differentially
      expressed genes.

PMID- 9159190
TI  - Regulation of involucrin gene expression by calcium in normal human
      keratinocytes.
AB  - Calcium is essential for normal epidermal differentiation. Data from Northern and
      nuclear run-on analysis indicate that involucrin gene transcription is induced by
      1.2 mM extracellular calcium. A 3.7 Kbp fragment of the involucrin gene, which
      contains 2.5 Kbp of upstream region, the transcription start site, and the first
      intron, was sub-cloned into the pGL3-basic luciferase reporter vector and
      transfected into pre-confluent normal human keratinocytes (NHK). The stimulated
      activities of this clone were above basal levels and was further enhanced eight
      fold by 1.2 mM extracelluar calcium. The results from a series of truncation and
      internal deletion experiments revealed multiple calcium-independent enhancer
      elements between -2476 and -2131 bp of the transcription start site and a calcium
      dependent element between -2131 and -2028 bp. This 103 bp fragment contains
      sequences of an AP-1 site (TGAGTCA), a SP-1 site (GGGCGG), and shares homology
      with two elements in the human keratin-1 promoter, within the regions identified
      as mediating the calcium responsiveness of that gene in keratinocytes. One or
      more of these putative elements may be involved in the calcium-dependent
      regulation of the involucrin gene transcription in NHK.

PMID- 9159191
TI  - Phagocytosis and intracellular killing of serum-opsonized Staphylococcus aureus
      by mouse fibroblasts expressing human Fcgamma receptor type IIa (CD32).
AB  - Phagocytes bear more than one class of receptors for the Fc domain of IgG
      (FcgammaR). In addition the same ligand can interact with different classes of
      FcgammaR. This complexity makes it difficult to study the contribution of the
      various classes of FcgammaR to antimicrobial functions. To circumvent this
      difficulty, in the present study mouse 3T6 fibroblasts transfected with cDNA
      encoding for human FcgammaR type IIa (FcgammaRIIa-expressing cells) were used to
      determine the role of this receptor in phagocytosis and intracellular killing of
      serum-opsonized Staphylococcus aureus. Experiments using microbiological and
      fluorescent techniques to discriminate between cell-adherent and intracellular
      bacteria revealed that serum-opsonized bacteria are phagocytized by FcgammaRIIa
      expressing cells, but not by parental fibroblasts. Non-opsonized bacteria were
      poorly internalized by FcgammaRIIa-expressing as well as parental fibroblasts.
      Furthermore, incubation of FcgammaRIIa-expressing cells with opsonized bacteria
      at 4oC and incubation of FcgammaRIIa-expressing cells with cytochalasin E prior
      to addition of opsonized bacteria inhibited the phagocytosis of these bacteria
      almost completely. Phagocytosis of opsonized bacteria by FcgammaRIIa-expressing
      cells was partly inhibited by selective inhibition of protein tyrosine kinases
      (PTK). FcgammaRIIa cross-linking initiated transient tyrosine phosphorylation of
      various proteins in FcgammaRIIa-expressing cells. These data indicate that
      activation of PTK is involved in the FcgammaRIIa-mediated phagocytosis of
      opsonized S. aureus by transfected fibroblasts. Human serum from normal
      individuals and agammaglobulinemic patients triggered the intracellular killing
      of S. aureus by FcgammaRIIa-expressing fibroblasts. Surprisingly, heat
      inactivated human serum, IgG and incubation with anti-FcgammaRII antibodies
      followed by a bridging secondary antibody did not stimulate the killing process.
      The possibility that these ligands did not interact with FcgammaRIIa on the cells
      can be excluded since they induced tyrosine phosphorylation of cellular proteins.
      The serum factor that stimulates the intracellular killing of bacteria by
      FcgammaRIIa-expressing cells is not yet identified. Oxygen-independent mechanisms
      are thought to be responsible for the killing of intracellular bacteria by these
      cells since the NADPH oxidase inhibitor diphenylene iodonium did not affect the
      serum-stimulated intracellular killing of S. aureus and no reactive oxygen and
      nitrogen intermediates were produced by FcgammaRIIa-expressing cells after
      appropiate stimulation. Taken together, these data show that phagocytosis but not
      intracellular killing of S. aureus is mediated via FcgammaRIIa on cells
      expressing this receptor.

PMID- 9159192
TI  - The first detection of complete androgen insensitivity with no mutation in the
      coding sequence of the androgen receptor gene.
AB  - We have analyzed the entire nucleotide sequences of complementary DNAs of the
      androgen receptor gene in two siblings (patients 8044 and 8047) with complete
      androgen insensitivity. Plasma testosterone was in the normal male range,
      however, androgen binding capacity was undetectable as measured in skin
      fibroblasts in both patients. 5alpha-reductase activity was normal in both cases
      confirming that this enzyme is not involved in the mechanism of androgen
      insensitivity. Northern blot analysis indicated that mRNA of the AR was normal in
      size. In addition, no mutation was found in the entire nucleotide sequences of
      complementary DNAs of the androgen receptor gene. Together, our results reveal an
      unusual insight into the molecular basis of androgen resistance, and the
      molecular heterogeneity in this clinical spectrum.

PMID- 9159194
TI  - A study of the interactions of an immunoglobulin light chain with artificial and
      B-lymphocyte membranes.
AB  - The binding of an immunoglobulin lambda light chain (IgLC) to synthetic and
      biological membranes was monitored in real-time using a recently developed, time
      resolved fluorescence technique. Lambda IgLC purified from the urine of patients
      with multiple myeloma, were used in studies of protein-membrane interactions. The
      association of the lambda IgLC dimer with B-lymphocytes was shown to be
      stabilised predominantly by non-polar interactions. Furthermore, it was found
      that following binding to synthetic phospholipid membranes, a reorientation of
      the light chain occurred which resulted in a change in the distribution of
      charged residues at the lipid-water interface. The rate constants associated with
      the binding event were calculated, and appear to comprise both temperature
      insensitive and sensitive components. The calculated activation energies of the
      binding and reorientation events were found to be 13.53 KJmol(-1) and 87.89
      KJmol(-1), respectively. The large activation energy associated with the
      reorientation phase suggests the movement of large protein domains, possibly
      involving a whole immunoglobulin domain. The binding and reorganisation of the
      IgLC upon the phospholipid membrane may confer novel biological functions to the
      bound protein and potentially contribute to such phenomenon as myeloma-associated
      immuno-suppression.

PMID- 9159193
TI  - Differential susceptibility to anti-receptor induced apoptosis in adult murine B
      cells: role of B1 cells.
AB  - We and others have recently found that mature murine B cells can be induced to
      undergo apoptosis, in vitro, in a dose-dependent manner, by extensive
      crosslinking of membrane IgM with polyclonal anti-mu. During the analysis of
      tolerance in transgenic mice expressing rearranged IgM or IgM + IgD receptors, we
      observed that, Sp6 anti-TNP Ig and anti-MHC transgenic splenocytes, would undergo
      receptor-mediated apoptosis in vitro just like their normal, non-transgenic
      littermates. However, transgenic mice expressing rearranged receptors typical of
      B1 cells, not only contained large numbers of CD5+ cells in their spleens, but
      these cells failed to undergo apoptosis under conditions that led to programmed
      cell death in normal splenocytes. B1 spleen cells also failed to proliferate with
      anti-IgM, although the responsiveness of cells from the other transgenic lines
      varied depending on the background strains. These differences are due in part, to
      strain differences, but they also imply that the response pattern of transgenic B
      cells reflects not only the subset composition in this organ, but also the
      transgenic specificity of the receptor.

PMID- 9159195
TI  - Deletion of the Herpes simplex 1 internal repeat sequences affects pathogenicity
      in the mouse.
AB  - We have isolated three different herpes simplex virus 1 (HSV-1) recombinant
      viruses, each frozen in either the P (prototype), IS (inversion of S component),
      or ILS (inversion of both components) genome arrangement. Common to all three
      recombinant viruses is the deletion of approximately 14 kilobases (kb) of viral
      DNA sequences representing greater than 95% of the internal repeat sequences and
      the insertion of a 9.6 kb mini-Mu genome containing a functional thymidine kinase
      gene. No unique DNA sequences were deleted from the viral genomes. Analyses of
      growth curves of the wild-type and recombinant viruses in cell culture has
      revealed that the recombinants grow somewhat more slowly, producing final titers
      within 1.5 logs of wild-type HSV-1(F). There is no discernible difference in
      plaque size or plaque morphology between the recombinant and wild type strains.
      Analysis of the recombinant viruses in mice reveals the following: I), the
      recombinant viruses are essentially avirulent, exhibiting drastically increased
      LD50 values as compared to the wild-type strain by intracerebral injection; ii),
      the recombinant viruses are not neuroinvasive in that they do not spread from the
      cornea to sensory ganglion; iii), the recombinant viruses exhibit minimal local
      replication both in the corneas of infected mice and in the brains of mice
      inoculated by intracerebral injection; and iv), the recombinant viruses do not
      establish a reactivable latent infection in the trigeminal ganglion following
      either intracerebral inoculation or inoculation of scarified corneas. These
      properties suggest a unique pattern of pathogenesis for HSV mutants in the mouse
      model.

PMID- 9159196
TI  - Transcutaneous electrosigmoidography. Study of the myoelectric activity of
      sigmoid colon by surface electrodes.
AB  - The purpose of this study was to determine the feasibilty of performing
      transcutaneous electrosigmoidography (TC-ESG). The study involved 19 healthy
      volunteers (11 men, 8 women; mean age 38.2 +/- 14.8 years). To validate the
      results of TC-ESG, the latter was performed simultaneously with intra-sigmoid
      ESG. TC-ESG was done also in five patients who underwent sigmoidectomy. The
      optimal position of the electrodes was determined after several trials. Two
      electrodes (Beckman) were applied, each 2-3 cm away from the middle of a line
      drawn from the umbilicus to the symphysis pubis. A third electrode was placed
      just above the symphysis pubis. A reference electrode was applied to one of the
      lower limbs. For intra-sigmoid IS-ESG, two silver-silver chloride electrodes were
      introduced from the anal orifice into the sigmoid colon and were attached to the
      mucosa by suction. Pacesetter potentials (PPs) were recorded as regular negative
      deflections. They had constant amplitude, frequency and velocity when recordings
      were obtained in the same subject. The PPs registered transcutaneously had the
      same amplitude, frequency and velocity as those recorded intrasigmoidally. Action
      potentials could be registered only intrasigmoidally and not transcutaneously. No
      electric waves could be recorded by TC-ESG in 5 patients who had undergone
      sigmoidectomy. In conclusion, TC-ESG is a simple, non-invasive and non-radiologic
      technique that can substitute intra-sigmoid ESG and potentially can be used in
      the diagnosis of various pathologic conditions of sigmoid colon.

PMID- 9159197
TI  - Comparison of contrast detail curves of full field digital with screen film
      breast phantom images.
AB  - In this investigation, we imaged a standard breast phantom and compared the
      contrast detail curves from a prototype full breast digital mammography system
      with the corresponding curves for a conventional, analog screen-film system. The
      full breast digital system exhibited superior contrast detail detectability. The
      results from this study will be used to plan future clinical evaluations
      comparing full breast digital and screen film mammography.

PMID- 9159198
TI  - Solid phase purification and SSCP analysis of amplified genomic DNA by capillary
      electrophoresis.
AB  - Detection and identification of point mutations in genomic DNA has proven
      increasingly important in biomedical research. A variety of methods for the
      analysis of single base substitutions have been proposed among which Single
      Strand Conformational Polymorphism (SSCP) quickly gained success due to its
      simplicity. In this work we present an analytical on-line tool which combines the
      ease of solid phase purification of amplified genomic DNA, the simplicity of SSCP
      and the significant potential advantages offered by capillary electrophoresis
      (CE).

PMID- 9159199
TI  - Experimental procedure for the detection of a rare human mRNA with the DIG
      System.
AB  - Newcomers to the DIG System often inquire about the possibility of performing
      Northern blot hybridizations with nonradioactive techniques. With the following
      examples, we would like to share our protocol for performing highly sensitive
      Northern blots. This procedure strictly adheres to the standard procedures
      detailed in our manuals and pack inserts, and there are no special "tricks"
      required. As a target, we have used total human skeletal muscle RNA (Clontech).
      We selected two probes: beta-actin and a probe comprising the cDNA of the
      transcription factor CTF1, which expresses a low abundant mRNA. We used in vitro
      transcribed RNAs exclusively as probes because, during the development of the DIG
      System, we have found that RNA probes exhibit a 10-100-fold higher sensitivity
      with RNA targets than do DNA probes. They are also less prone to background
      problems caused by probe concentrations that are too high. For DNA probes, we
      recommend an optimal probe concentration of 25 ng/ml. Using a probe concentration
      that is even slightly too high (e.g., 1.5 fold) will dramatically increase the
      background. For RNA probes, we recommend an optimal probe concentration of 100
      ng/ml, which will not lead to background problems. In the following examples, we
      describe all experimental details, starting from the gel run for the blot.

PMID- 9159200
TI  - The foundations of successful RT in situ PCR.
AB  - RT in situ PCR allows for the routine and rapid detection of low copy viral and
      human RNAs. Success with RT in situ PCR is best accomplished with formalin fixed,
      paraffin embedded material, which allows the study of archival material. The key
      variable for RT in situ PCR is protease digestion. The optimal digestion time,
      which is determined by testing a variety of protease digestion times, is defined
      by an intense signal in the nuclei of most cells irrespective of the primers
      used, and a loss of this signal with overnight digestion in DNase. This permits
      the target specific direct incorporation of the labeled nucleotide into the
      amplified cDNA. A lack of signal with the negative control (DNase, no RT) and an
      intense nuclear signal in most cells with the positive control (no DNase) is
      prerequisite for success with RT in situ PCR. The localization of the signal
      (cytoplasmic for human mRNAs and restricted to certain cell types) is another
      important indicator of successful RT in situ PCR. The one step rTth system allows
      for the reproducible amplification and detection of low copy RNA targets within a
      few hours. Matrix metalloprotease (MMPs) and their inhibitors (TIMPs) in cervical
      cancer are used as a model system for RT in situ PCR. Analysis of MMP and TIMP
      expression in cervical cancer demonstrates the following: 1) the signal localizes
      to the cytoplasm of invasive cancer cells and the surrounding stromal cells; 2)
      no signal is evident in the adjacent carcinoma in situ cells (non invasive
      component) or the normal epithelium. Cervical cancers of poor prognosis showed a
      marked increase in the percentage of cells expressing MMP versus TIMP as compared
      to microinvasive cervical cancer, which has an excellent prognosis.

PMID- 9159201
TI  - Rapid purification of histidine-tagged glutathione S-transferase fusion protein
      by metal chelate POROS perfusion chromatography media.
AB  - The use of POROS MC media allowed high speed column preparation, sample loading,
      and elution. Under these conditions the proteins of interest can be recovered
      under mild conditions to maintain maximum biological activity. The speed of the
      process also assures minimum degradation or post-extraction modifications of the
      protein of interest from exposure to naturally occurring proteases and other
      enzymes. It is evident from the analysis by polyacrylamide gel electrophoresis of
      the purified fusion protein and starting material that a high degree of
      purification is possible in a single high-speed separation on POROS MC. The high
      flow rate capabilities of POROS media offer several other significant advantages
      over conventional media. A few of these include high speed and systematic method
      optimization, rapid column preparation and sample loading, and fast time-saving
      chromatographic separations.

PMID- 9159202
TI  - The molecular basis of ovarian cell death during germ cell attrition, follicular
      atresia, and luteolysis.
AB  - Physiological cell death mechanisms (termed apoptosis, programmed cell death,
      active cell death, and biological cell death) play a fundamental role in the
      cyclic function of the ovary as it strives in each cycle to ovulate a viable egg
      for fertilization. Healthy ovarian follicles and corpora lutea are also required
      for the secretion of steroids to prepare the female reproductive tract for embryo
      implantation and gestation. Using molecular biological approaches combined with
      classic histological examinations, several recent studies have confirmed the
      occurrence of apoptosis in female germ cells (oogonia and oocytes) during fetal
      ovarian development, granulosa cells during follicular atresia, and cells of the
      corpus luteum during luteolysis. Additionally, new light has been shed on the
      potential gene products which function to precisely coordinate the balance of
      life and death in the ovary. It is the purpose of this review to discuss the
      concepts of physiological cell death as they relate to ovarian function, and to
      offer testable hypotheses concerning the intracellular effector pathways
      responsible for directing ovarian cell fate in response to changes in hormonal
      stimuli.

PMID- 9159203
TI  - Immune regulation by CD40-CD40-L interactions.
AB  - CD40 is a cell surface receptor, which belongs to the TNF-R family, and which was
      first identified and functionally characterized on B lymphocytes. However, in
      recent years it has become clear that CD40 is expressed much broader, including
      expression on monocytes, dendritic cells, endothelial cells and epithelial cells.
      Therefore it is now thought that CD40 plays a more general role in immune
      regulation. The present paper reviews recent developments in this field of
      research, with main emphasis on 1) structure and expression of CD40 and its
      ligand; 2) CD40 signal transduction; 3) in vitro function of CD40 on different
      cell types; 4) in vivo functions of CD40/CD40-L interactions.

PMID- 9159204
TI  - Soluble Fas/Apo-1 splicing variants and apoptosis.
AB  - In addition to the full length mRNA activated human peripheral blood mononuclear
      cells (PBMC) and T cell tumor lines express several alternatively spliced Fas
      variants. At least five of these code for soluble Fas (CD95) molecules. In vitro
      studies suggest that these soluble Fas isoforms inhibit apoptosis induced by
      agonistic antibodies and, more importantly, by the natural Fas ligand in Fas
      bearing sensitive cells. Interestingly, this functional property can be assigned
      to the first 49 aminoacids of the mature protein, the only region shared by the
      soluble Fas molecules.

PMID- 9159205
TI  - Cytokines in acute and chronic inflammation.
AB  - Inflammation is mediated by a variety of soluble factors, including a group of
      secreted polypeptides known as cytokines. Inflammatory cytokines can be divided
      into two groups: those involved in acute inflammation and those responsible for
      chronic inflammation. This review describes the role played in acute inflammation
      by IL-1, TNF-alpha, IL-6, IL-11, IL-8 and other chemokines, G-CSF, and GM-CSF. It
      also describes the involvement of cytokines in chronic inflammation. This latter
      group can be subdivided into cytokines mediating humoral responses such as IL-4,
      IL-5, IL-6, IL-7, and IL-13, and those mediating cellular responses such as IL-1,
      IL-2, IL-3, IL-4, IL-7, IL-9, IL-10, IL-12, interferons, transforming growth
      factor-beta, and tumor necrosis factor alpha and beta. Some cytokines, such as IL
      1, significantly contribute to both acute and chronic inflammation. This review
      also summarizes features of the cell-surface receptors that mediate the
      inflammatory effects of the described cytokines.

PMID- 9159206
TI  - Microinjection strategies for the study of mitogenic signaling in mammalian
      cells.
AB  - First used in the analysis of dynamic changes in cell structure, microneedle
      microinjection allows in situ study of individual living cells as opposed to
      large scale metabolic analysis of heterogeneous cell culture. In addition,
      microinjection also offers the possibility to examine in vivo regulated processes
      by modulating the intracellular levels and activity of key regulatory proteins
      and genes in both a specific and controlled manner. A number of different
      strategies have been developed over the past 5 years to examine the pathways and
      effectors that are involved in mitogenic signaling as well as in the regulation
      of gene expression during the proliferative response to growth factors by normal
      fibroblasts. These strategies include: 1. Direct in vivo competition for various
      trans-activating DNA binding activities by microinjection of double-stranded
      oligonucleotides, microinjection of monospecific antibodies against transcription
      factors and microinjection of dominant negative mutants of transcription factors
      based upon their DNA binding domain. 2. Microinjection of purified enzymes
      (kinases and phosphatases) or peptides and antibodies that specifically inhibit
      these activities. 3. Microinjection of expression plasmids which encode various
      normal and epitope-tagged regulatory molecules. In many of the experiments
      described below, c-fos gene expression was monitored as an early marker of
      mitogenic response. The c-fos gene belongs to a family of genes whose
      transcription is activated very early after addition of growth factor (1-4). For
      in vivo studies, the c-fos promoter offers several unique advantages. Primarily,
      it is easy to manipulate. In practical terms, when mammalian fibroblasts are made
      quiescent (by replacing the normal growth media, with growth factors-depleted
      media) and subsequently activated by re-adding mitogen (growth factors, serum), c
      fos RNA expression is restored within 15 minutes and the protein is specifically
      detected in the nuclei of cells after 90 minutes, but is no longer detectable
      after 3 hours. Secondly, results obtained with the c-fos promoter are directly
      applicable to cell growth since expression of c-fos is itself a prerequisite for
      proliferation as demonstrated by microinjection of anti-fos antibodies which
      prevented proliferation in mammalian cells (5). Thirdly, the c-fos promoter is
      exquisitely sensitive to agents which cause cell stress. In this respect, heat
      shock, poor microinjection or microinjection in the presence of heavy metals or
      chelating agents in the culture media all rapidly stimulate c-fos expression.
      However, when compared to c-fos expression in the proliferative response, stress
      mediated c-fos expression is induced both more rapidly and strongly, reverses
      more slowly (the protein is still detectable after 5-6 hours) and does not result
      in cell proliferation (unpublished observation). As such, it provides an
      excellent internal control for identifying poor treatment and manipulation of
      cells . Finally, the c-fos promoter is subject to several levels of auto
      regulation enabling the analysis of not only components involved in
      transcriptional activation , but also various aspects of transcriptional down
      regulation and shut-off.

PMID- 9159207
TI  - BTK, the tyrosine kinase affected in X-linked agammaglobulinemia.
AB  - X-linked agammaglobulinemia (XLA) is a heritable immunodeficiency disorder that
      is caused by a differentiation block leading to almost complete absence of B
      lymphocytes and plasma cells. The affected protein is a cytoplasmic protein
      tyrosine kinase, Bruton's agammaglobulinemia tyrosine kinase (Btk). Btk along
      with Tec, Itk and Bmx belong to a distinct family of protein kinases. These
      proteins contain five regions; PH, TH, SH3, SH2 and kinase domains. Mutations
      causing XLA may affect any of these domains. About 200 unique mutations have been
      identified and are collected in a mutation database, BTKbase. Here, we describle,
      the structure, function, and interactions of the affected signaling molecules in
      atomic detail.

PMID- 9159208
TI  - Apoptosis in renal diseases.
AB  - Abnormalities of cell number are a frequent feature of renal disorders. Cell
      death is a key factor in the regulation of cell number. Apoptosis is an active
      form of cell death that is modulated by extracellular lethal and survival
      signals. Regulation of apoptosis also involves a complex system of sensors of the
      extracellular signals, triggers of the apoptosis program, effectors of apoptosis
      as well as intracellular survival factors. This paper first reviews current
      knowledge on the regulation of apoptosis with particular emphasis on renal cell
      death. Subsequently, it deals with the role of apoptosis in triggering renal
      disease and its participation in the progression and resolution of renal
      disorders. This section includes information on the occurrence of apoptosis and
      expression of apoptosis-related genes in glomerular injury, acute renal failure,
      chronic renal atrophy, renal fibrosis, polycystic renal disease and kidney
      development. The final section presents an overview of possible approaches to the
      therapeutic manipulation of apoptosis in the kidney.

PMID- 9159209
TI  - Role of cholesterol in the regulation of renal phosphate transport.
AB  - The kidney plays a critical role in the regulation of inorganic phosphate (Pi)
      homeostasis through changes in the proximal tubular apical membrane Na-dependent
      Pi (Na/Pi) transport activity. In response to alterations in dietary Pi intake
      and during the aging process, changes in renal Na/Pi transport activity are
      inversely correlated with apical membrane cholesterol content. Cholesterol
      regulates Na/Pi transport activity by fluidity-dependent and fluidity-independent
      mechanisms, including regulation of Na/Pi protein transcription, synthesis, and
      trafficking to and from the plasma membrane.

PMID- 9159210
TI  - DnaA- and PriA-dependent primosomes: two distinct replication complexes for
      replication of Escherichia coli chromosome.
AB  - Enzymatic analyses of primosome assembly at chromosomal and plasmid origins as
      well as that at single-stranded replication origins revealed the presence of two
      distinct primosomes in Escherichia coli for primer RNA synthesis and duplex
      unwinding. A DnaA-dependent primosome is assembled at oriC, the chromosomal
      origin of Escherichia coli, as well as at the A site, a single-stranded DNA
      hairpin containing a dnaA box sequence within its stem. In contrast, PriA protein
      recognizes a hairpin, called n'-pas (primosome assembly site), and initiates
      assembly of the phiX174-type PriA-dependent primosome in conjunction with other
      prepriming proteins. Genetic analyses of the prepriming proteins required
      specifically for the latter primosome strongly suggested that it is responsible
      for RecA-dependent, DnaA/oriC-independent replication of the Escherichia coli
      chromosome. Furthermore, primosome assembly in replication of various plasmids
      may also be classified into either DnaA-dependent or PriA-dependent type. We
      propose that Escherichia coli possesses two distinct, mutually exclusive
      primosomes which are differentially utilized by the chromosome as well as by the
      plasmids. PriA protein appears to be conserved in a wide range of prokaryotic
      species, and we will also discuss possible biological function of the PriA
      dependent primosome in the process of responses to DNA damages.

PMID- 9159211
TI  - Role of NF-kappaB in the control of apoptotic and proliferative responses in IL-2
      responsive T cells.
AB  - The NF-kappaB/Rel/IkappaB family of transcription factors regulates a number of
      genes involved in a wide variety of biological processes. The activation of p53,
      c-myc and Ras genes suggests a role for NF-kappaB in cell proliferation; NF
      kappaB is also important in immune and inflammatory responses. By virtue of its
      role in apoptosis, NF-kappaB participates in the thymus as well as in embryonic
      development. The NF-kappaB family of transcription factors is also involved in
      viral transcription, transformation and in the development of some types of human
      cancers. Given the pivotal role of NF-kappaB, clarification is needed of the
      mechanisms through which its deregulation contributes to disease. Several aspects
      of NF-kappaB regulation, such as phosphatase involvement, the mechanism of
      IkappaB ubiquitination and the regulation of nuclear translocation, remain
      obscure. Here, we review and discuss the function of NF-kappaB activation in IL-2
      stimulation and in apoptosis induced by IL-2 deprivation in T cells.

PMID- 9159212
TI  - The androgen receptor: a mediator of diverse responses.
AB  - Androgens mediate a number of diverse responses through the androgen receptor, a
      110 kD ligand-activated nuclear receptor. Androgen receptor expression, which is
      found in a variety of tissues, changes throughout development, aging, and
      malignant transformation. The androgen receptor can be activated by two ligands,
      testosterone and dihydrotestosterone, which bind to the androgen receptor with
      different affinities. This difference in binding affinity results in different
      levels of activation of the androgen receptor by the two ligands. The androgen
      receptor acts as a transcriptional modifier of a variety of genes by binding to
      an androgen response element. The ability to confer androgen specific actions by
      the androgen response element may depend on other cell-specific transcription
      factors and cis-acting DNA elements in close proximity to it. Testosterone and
      dihydrotestosterone appear to act upon an identical nuclear receptor. However, in
      certain instances, they mediate different physiologic responses. For example,
      dihydrotestosterone, but not testosterone, is capable of mediating full sexual
      development of the male external genitalia. In some cases, the androgen receptor
      may induce opposite physiologic responses in similar tissue types depending on
      their location. For example, in male pattern baldness, activated androgen
      receptors may suppress the growth of distinct hair follicle populations through
      initiating stromal-epithelial actions, whereas other hair follicles continue to
      proliferate. In other cases, altered androgen receptor activity due to its
      mutation or altered expression may lead to pathology such as recurrence of
      prostate cancer due to development of androgen independence allowing tumor cell
      proliferation under androgen deprivation.

PMID- 9159213
TI  - Antigen-induced death of T-lymphocytes.
AB  - Resting mature T-lymphocytes are activated when they are triggered via their
      antigen-specific T-cell receptor (TCR) molecule or the associated CD3 antigen. In
      contrast, preactivated T-cells can undergo activation-induced cell death (AICD)
      in response to the same signals. Stimulation of activated T-cells upregulates the
      expression of the Fas-ligand, and the interaction of Fas-ligand with the
      corresponding Fas receptor triggers an apoptosis program that culminates in
      cellular suicide usually associated with the fragmentation of DNA into
      oligonucleosomal bands. Molecular evidence indicates that proteases related to
      interleukin-1-beta converting enzyme play an essential role in the execution of
      cell death. AICD of mature T-lymphocytes can be efficiently triggered by
      monoclonal antibodies against the CD3/TCR complex, or by superantigens such as
      bacterial enterotoxins. Although it is more difficult to induce AICD by
      conventional peptide antigens, it is now clear that antigen-induced AICD is a
      powerful means of eliminating antigen-reactive T-cells. Therefore, AICD
      contributes to the regulation (i.e., termination) of cellular immune responses.
      In addition, AICD might play a role in the establishment of peripheral immune
      tolerance. Increased knowledge of the molecular mechanisms of AICD opens new
      immunotherapeutical perspectives for the treatment of certain autoimmune
      diseases, and will have implications in other areas such as transplantation
      medicine.

PMID- 9159214
TI  - Interactions between the components of the human NADPH oxidase: a review about
      the intrigues in the phox family.
AB  - When microorganisms invade the body, they encounter a large asssortment of
      defense mechanisms. Among these, phagocytes play an important role in the process
      of killing pathogens. This event is mediated by two important processes, viz.
      activation of the NADPH oxidase enzyme, which leads to the production of toxic
      oxygen metabolites, and fusion of intracellular granules with the phagosome (the
      vesicle that contains the ingested micro-organisms), which causes release of the
      toxic granule contents into this vesicle. The human NADPH oxidase is a very
      complex enzyme, in two ways: 1. it exists of at least 6 components: cytochrome
      b558 (a heterodimer comprised of gp91-phox and p22-phox), p47-phox, p67-phox, p40
      phox, rac and Rap1A, and 2. there are multiple signal transduction pathways
      leading to activation of the NADPH oxidase. The most likely reason for this
      complexity is the toxicity of the oxygen radicals produced by the active NADPH
      oxidase; these compounds are not only harmful to the invading pathogens, but also
      to the surrounding tissues. This latter effect is enforced by the activation of
      metalloproteases released by neutrophils and by oxidation of protease inhibitors
      by oxygen metabolites. Therefore, an improper activation of the NADPH oxidase
      must be prevented at all costs and, when the infection has been cleared, a rapid
      deactivation mechanism is imperative. In this review, the interaction between the
      different components of the NADPH oxidase and the activation of these proteins
      will be discussed.

PMID- 9159215
TI  - Mast cells as modulators of host defense in the lung.
AB  - Mast cells display a distinct spatial distribution in the lung where they are
      found preferentially in intraepithelial locations or in deeper tissue around
      blood vessels, bronchioles and mucus secreting glands. Yet the physiological role
      of these granule-laden cells is unknown. There are now intriguing signs that
      their distinctive distribution together with their intrinsic capacity to release
      large amounts of inflammatory mediators serve a critical role in immune
      surveillance. Mast cells have now been shown to be capable of recognizing and
      aggressively reacting to a wide range of bacteria. The mast cell responses
      involve ingesting and killing of adherent bacteria, in a manner not unlike that
      of traditional phagocytic cells. Concomitant with this endocytic activity, a
      large variety of potent inflammatory mediators are released by the mast cell. One
      such mast cell-derived mediator, TNF-alpha, was recently shown to be a critical
      signal for initiating neutrophil influx to sites of bacterial infection in the
      lung as well as the peritoneum of mice. This capacity of mast cells to recruit
      neutrophils, together with its recently reported participation in processing and
      presenting bacterial antigens to immune cells and in mediating proliferation of
      epithelial cells and mucosal mucus secretion, indicate that mast cells have an
      extraordinary ability to modulate the innate as well as adaptive immune responses
      to infectious microorganisms.

PMID- 9159217
TI  - The pattern and mechanism of mitochondrial transport in axons.
AB  - Mitochondria in nerve axons display motility behavior that is as distinctive as
      their metabolic function. Unlike many other classes of organelles, mitochondria
      undergo net movement that is the sum of movements in both the anterograde and
      retrograde directions, and their net velocity is strongly influenced by their
      recruitment between stationary and motile states. They recently became the first
      specific class of organelle shown to be capable of moving along either
      microtubule or F-actin tracks in the axon, indicating that they probably use a
      diversity of molecular motors. Although we still know relatively little about how
      the movement of specific classes of axonal organelles is coordinated with their
      function in the neuron, in the case of mitochondria it is at least clear that
      their transport delivers them to regions of the neuron where ATP consumption is
      likely to be high, and disperses them when local energy needs change. In
      addition, although mitochondria contain both anterograde and retrograde motor
      activities, the modulation of their motility necessary to achieve these
      redistributions seems to rely largely upon regulation of the anterograde motor
      activity alone. A further element in the regulation of their motility and
      distribution is the apparent "docking" of mitochondria to microtubules or
      neurofilaments, a phenomenon which may serve to stabilize their distribution once
      regulated motility has moved them to appropriate sites. This review considers the
      current state of knowledge in these areas with an emphasis on the pattern of
      regulation of motility and how it underlies the role of mitochondria as the
      aerobic ATP source of the neuron.

PMID- 9159216
TI  - Cross-talk signals in the CNS: role of neurotrophic and hormonal factors,
      adhesion molecules and intercellular signaling agents in luteinizing hormone
      releasing hormone (LHRH)-astroglial interactive network.
AB  - Neuron-astrocyte interactions play a crucial role during development and in the
      adult brain. During development, glial cells are involved in the guidance of
      neuronal precursors and in extending neuronal fiber projections. Astrocytes can
      promote neurite outgrowth, both "in vitro" and "in vivo". In the central nervous
      system (CNS), they express receptors for a variety of growth factors (GFs),
      neurotransmitters and/or neuromodulators. In turn, neuronal cells can respond to
      astrocyte-derived growth factors and control astrocyte function via a common set
      of signaling molecules and intracellular transducing pathways. It is also well
      established that astrocytes are involved with regenerative failure within the CNS
      following injury. Increasing evidence support the viewpoint that soluble factors
      from lymphoid/mononuclear cells modulate the growth and function of cells found
      in the CNS, specifically macroglia and microglia cells. Furthermore, glial cells
      can secrete immunoregulatory molecules that influence immune cells, as well as
      the glial cells themselves. In recent years, a bi-directional flow of
      informational molecules between LHRH neurons, subserving the neuroendocrine
      control of reproductive function, and astroglia cells has been disclosed. During
      their maturation and differentiation in vitro, astroglial cells release peptide
      growth factors that markedly accelerate LHRH neuronal phenotypic differentiation
      . In addition, these peptides induce the acquisition of mature LHRH secretory
      potential, with a potency depending on both the "age" and the specific brain
      localization of the astroglia, as well as the degree of LHRH neuronal
      differentiation "in vitro". Different experimental paradigms such as co-culture
      and mixed culture models between the GT1-1 neurons and astroglial cells in
      primary culture, disclosed the presence of a bi-directional flow of informational
      molecules regulating both proliferative and secretory capacities of each cell
      type. Growth factors are key players in LHRH neuron-astroglia crosstalk. In
      particular, basic fibroblast growth factor (bFGF) was identified as a major
      differentiation factor for the immortalized hypothalamic LHRH neuronal cell line.
      A specific synergy/cooperation between bFGF and other growth factors was also
      revealed at specific stages of LHRH neuron differentiation, indicating that the
      sequential expression of specific growth factors may participate in the processes
      of LHRH neuron migration, differentiation and functional regulation. Since bFGF
      is expressed in GT1-1 neurons and glial cells a possible paracrine/autocrine
      regulatory loop is suggested. Indeed, neutralization experiments aimed at
      counteracting endogenous bFGF during neuron-glia interactions dramatically
      inhibited astroglia neurotrophic effects. On the other hand, the importance of
      adhesion molecules in cell-to-cell communication was underscored by the
      significant inhibition of GT1-1 LHRH production and cell proliferation following
      the counteraction of neuron-neuron/neuron-glia interactions through addition of
      neuronal cell adhesion molecule (N-CAM) antiserum. Other information came from
      pharmacological experiments manipulating the astroglial-derived cytokines and/or
      nitric oxide, which revealed a crosstalk between the neuronal and astroglial
      compartments. From the bulk of this information, it seems likely that
      interactions between astroglia and LHRH neurons play a major role in the
      integration of the multiplicity of brain signals converging on the LHRH neurons
      that govern reproduction.

PMID- 9159218
TI  - Membrane lipid dynamics during human sperm capacitation.
AB  - Sperm membranes have an unusual lipidic composition which is distinct from those
      of mammalian somatic cells. They have high levels of plasmalogens, a kind of
      ether-linked lipids, and a high content of polyunsaturated fatty acyl groups.
      Plasmalogens may form non-diffusible membrane regions or domains, whereas
      polyunsaturated ethanolamine plasmalogens are known to destabilize the lipidic
      bilayer. During transit of sperm through the female reproductive tract, sperm
      coating proteins bind to heparin-like glycosaminoglycans. An essential feature of
      capacitation is the removal of cholesterol from the acrosomal membrane of sperm.
      Albumin and high-density lipoproteins present in the uterine and follicular fluid
      act as cholesterol acceptors. Plasma membrane of sperm organize in large non
      diffusible lipid domains. This regionalization affects the distribution of both
      lipids and proteins. A barrier to lateral diffusion of lipids and proteins in the
      equatorial segment has been reported and contributes to the formation of
      macrodomains. Lateral separation into cholesterol-rich and cholesterol-depleted
      microdomains could also be created. Cone-shaped phospholipids induce the
      formation of non-bilayer phases and might facilitate membrane fusion. This review
      will discuss the removal of coating proteins, cholesterol efflux, domain
      organization, relocalization of lipids and proteins and the role of fusogenic
      lipids during capacitation.

PMID- 9159219
TI  - The tau proteins in neuronal growth and development.
AB  - The neuronal microtubule-associated protein tau has been implicated as having a
      role in the outgrowth of neural processes and the development of neuronal
      polarity. In vitro, tau promotes microtubule assembly, stabilizes cellular
      microtubules, and affects their dynamic behavior. Antisense experiments using
      cultured neurons provided evidence for an essential role of tau in the
      development of axons. However, tau knockout mice turned out to be surprisingly
      healthy and developed neurons which were functionally and structurally almost
      normal. This raises the question of how essential tau is for neuronal
      development. In the first part of this paper, data on the function of tau as a
      microtubule assembly-promoting and stabilizing factor are reviewed. Then, studies
      investigating the role of tau in the development of neuronal polarity are
      discussed. In the last part, recent results which provide evidence for a role of
      tau not directly related to its activity on microtubule assembly are summarized.

PMID- 9159220
TI  - Fibronectin-integrin interactions.
AB  - Fibronectin is recognized by at least ten cell surface receptors of the integrin
      family. Most cell types in the body can adhere to fibronectin via these
      receptors, and thereby fibronectin becomes involved in many different biological
      processes. Three areas related to fibronectin and its receptors which have
      developed rapidly during the last few years are summarized in this review: the
      mechanisms of interactions between fibronectin and integrins, fibronectin
      polymerization, and in vivo functions of the proteins as studied by gene
      targeting in mice.

PMID- 9159221
TI  - New insights on molecular pathways utilized by salmonella species in cell
      binding.
AB  - Salmonella infections are a principal source of gastroenteritis and enteric fever
      in a variety of animals, including humans. An essential step in the development
      of Salmonella pathogenesis is the entry of bacteria into non-phagocytic cells,
      including those that line the intestinal epithelium. As a consequence of specific
      cues from the host intestinal micro-environment, Salmonella entry into the
      intestinal epithelium is the product of a multistep process that culminates in
      host cell membrane ruffling, and subsequent bacterial uptake. The events that
      trigger the internalization event appear to require an array of bacterial
      secreted proteins, exemplified by the formation of bacterial surface appendages
      (invasomes) which are important for the induction of host-cell signal
      transduction pathways that lead to membrane ruffling. In addition, during
      intestinal disease states induced by Salmonella typhimurium, transepithelial
      migration of neutrophils rapidly follows attachment of the bacteria to the
      epithelial membrane. Current evidence indicates that the intestinal epithelium
      plays a key role in orchestrating the inflammatory response to surface attached
      S. typhimurium. In this review, we explore current insights on the molecular
      pathways utilized by Salmonella spp. in cell binding that are important not only
      in the processes of Salmonella internalization but also in the generation of
      signals which lead to active states of intestinal inflammation.

PMID- 9159222
TI  - Interaction of human spermatozoa with the zona pellucida of oocyte: development
      of the acrosome reaction.
AB  - Mammalian spermatozoa are not able to fertilize an oocyte upon ejaculation. To
      gain fertilizing ability, spermatozoa must, either in vivo or in vitro, undergo a
      process termed capacitation. Since a reliable marker for capacitation does not
      exist, it is considered that this process is completed when the spermatozoa are
      able to undergo acrosomal x intestinal mucosa which might require tandem
      signaling events for this process is the presence of a vascular countercurrent
      arrangement in the subepithelial compartment. As happens for absorbed solutes,
      this countercurrent phenomenon may distort transepithelial solute gradient. For
      example, perfusion of mammalian intestinal loops in vivo with solutions
      containing fMLP was previously found to induce neutrophil attachment to
      endothelial cells and structurally defined endothelial activation, but failed to
      elicit directed migration across the lamina propria (Madara, unpublished
      observations), suggesting that directed migration may require a more stable
      gradient than that afforded by the usual soluble signals. For example, once
      present in inflamed tissue, IL-8 is likely to retain its biological activity for
      several hours, as shown by local intradermal administration in animals and
      humans. In contrast to Il-8, chemokines such as fMLP or LTB4 are degraded rapidly
      by oxidation or hydrolysis. Fertilization is a very complex phenomenon, involving
      sequential interactions between the fertilizing spermatozoon and cumulus
      oophorus, ZP, and oolemma. The AR may be playing a key role in penetration of
      spermatozoa through these egg vestments.

PMID- 9159223
TI  - Pathogenesis and treatment of HIV-1 infection: recent developments.
AB  - Human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of acquired
      immunodeficiency syndrome (AIDS) and is estimated to presently infect 24 million
      adults and 1.5 million children, worldwide. The pathogenesis of HIV-1-induced
      disease is complex and characterized by the interplay of both viral and host
      factors, which together determine the outcome of infection. An improved
      understanding of the pathogenic mechanisms of AIDS, combined with recent insights
      into the dynamics of viral infection, and the cellular co-receptors for HIV-1,
      may provide powerful new opportunities for therapeutic intervention against this
      virus.

PMID- 9159224
TI  - Signal transduction in pancreatic beta-cells: regulation of insulin secretion by
      information flow in the phospholipase C/protein kinase C pathway.
AB  - The physiologic regulation of glucose-induced insulin secretion is dependent upon
      the activation of information flow in the phospholipase C (PLC)/protein kinase C
      (PKC) signal transduction system. In both rat and human pancreatic beta-cells,
      glucose has several time-dependent effects on secretory responsiveness including
      the regulation of biphasic insulin secretion, time-dependent potentiation and
      time-dependent suppression. PLC/PKC activation has been implicated in all three
      response patterns. Islets of Langerhans contain the three major PLC isozyme
      classes (beta1, gamma1 and delta1) and the available evidence suggests that one
      class is activated by fuel secretagogues and another by neurohumoral agonists.
      The expression and activation of PLC is labile. When rat islet are cultured for
      short periods, the content and activation of PLC in response to glucose decreases
      and this biochemical defect in signal transduction is paralleled by significant
      reductions in glucose-induced insulin secretion. Similar defects are observed
      when human islets are cultured as well. Mouse islet responses to glucose
      stimulation differ in several major and dramatic ways from rat and human islet
      responses. When stimulated by 15mM glucose, mouse islets fail to develop a rising
      second phase secretory response, they fail to exhibit either time-dependent
      potentiation or time-dependent suppression to the hexose. Biphasic insulin
      secretion can be evoked and time-dependent potentiation can be induced in mouse
      islets by carbachol, an agonist that activates an isozyme of PLC distinct from
      that activated by glucose. These divergent response patterns are attributable to
      the underexpression in mouse islets, when compared to rat islets, of a fuel
      sensitive PLC isozyme. When taken in their entirety, the experimental evidence
      suggests that the activation of PLC is an essential component in the physiologic
      regulation of insulin secretion and that disordered activation of the enzyme
      culminates in disordered insulin release.

PMID- 9159225
TI  - Adhesion molecules in human sperm-oocyte interaction: relevance to infertility.
AB  - Fertilization involves cell-cell fusion of a sperm with the oocyte. This fusion
      restores the diploid genome, activates the oocyte, and initiates embryonic
      development. The identification of proteins mediating the fusion of sperm with
      oocyte plasma membrane (oolemma) is important to a deeper knowledge of
      fertilization. Defects in sperm-oocyte fusion may account for some form of human
      infertility. The hypothesis that sperm plasma membrane and oolemma carry
      complementary molecules involved in multistep fusion process has been validated
      by studies of cell adhesion molecules (integrins) in sperm-oocyte interaction in
      a number of animal models and human in vitro fertilization assays. Integrins or
      integrin-like molecules and complement proteins present on the surface of
      mammalian gametes, might be involved in the interaction between oocyte and sperm
      at fertilization. This review will provide an overview of the interaction of
      human sperm membrane with the oolemma, the nature of cell adhesion molecules,
      their expression profiles and their possible involvement in adhesive and
      fusogenic events in human fertilization. Unraveling the unique molecules involved
      in human sperm plasma membrane-oolemma fusion will be an important component for
      the development of a new set of contraceptive vaccines.

PMID- 9159226
TI  - New mechanisms of regulation of the genomic actions of vitamin D in bone cells:
      interaction of the vitamin D receptor with non-classical response elements and
      with the multifunctional protein, calreticulin.
AB  - Vitamin D exerts its genomic effects following binding to a specific receptor
      which is a member of the steroid hormone receptor superfamily. The vitamin D
      receptor (VDR) forms heterodimers with retinoid X receptors (RXRs) and the dimer
      then interacts with its cognate binding site, termed vitamin D response element
      (VDRE), to affect the transcription of target genes. Recent studies have
      identified novel sequence motifs for VDREs as well as novel protein-protein
      interactions involving the VDR. These will be reviewed with particular emphasis
      on the complex VDRE from the c-fos proto-oncogene promoter region and the
      inhibition of the vitamin D signal transduction pathway by the multifunctional
      protein, calreticulin. Thus research on the control of gene transcription by
      vitamin D reveals examples of molecular interplay between transcriptional
      regulatory pathways and provides new insight into the molecular mechanism of
      action of vitamin D.

PMID- 9159227
TI  - Human sperm activation during capacitation and acrosome reaction: role of
      calcium, protein phosphorylation and lipid remodelling pathways.
AB  - Two processes, namely capacitation and acrosome reaction, are of fundamental
      importance in the fertilization of oocyte by spermatozoon. Physiologically
      occurring in the female genital tract, capacitation is a complex process, which
      renders the sperm cell capable for specific interaction with the oocyte. During
      capacitation, modification of membrane characteristics, enzyme activity and
      motility property of spermatozoa render these cells responsive to stimuli that
      induce acrosome reaction prior to fertilization. Physiological acrosome reaction
      occurs upon interaction of the spermatozoon with the zona pellucida protein ZP3.
      This is followed by liberation of several acrosomal enzymes and other
      constituents that facilitate penetration of the zona and exposes molecules on the
      sperm equatorial segment that allows fusion of sperm membrane with the oolemma.
      The molecular mechanisms and the signal transduction pathways mediating the
      processes of capacitation and acrosome reaction are only partially defined, and
      appear to involve modifications of intracellular calcium and other ions, lipid
      transfer and phospholipid remodelling in sperm plasma membrane as well as changes
      in protein phosphorylation. The human and mouse sperm receptor for ZP3 has been
      recently sequenced and cloned. This receptor exhibits sequence homology with
      proto-oncogenes that mediate proliferation and differentiation in somatic cells.
      This review summarizes the main signal transduction pathways involved in
      capacitation and acrosome reaction.

PMID- 9159228
TI  - Involvement of protein tyrosine phosphorylation of human sperm in
      capacitation/acrosome reaction and zona pellucida binding.
AB  - The aim of this article is to review the surface molecules that are involved in
      capacitation/acrosomal exocytosis and zona pellucida (ZP) binding in context of
      tyrosine phosphorylation leading to signal transduction in human sperm. During
      capacitation, at least 7 proteins (200, 112, 104, 48, 42, 31 and 25 kD) are
      phosphorylated as studied by the 32P metabolic labeling assay, and 14 proteins
      (122, 105, 95, 89, 73, 62, 48, 46, 40, 33, 30, 28, 25 and 22 kD) are
      autophosphorylated as demonstrated in the in vitro kinase assay. Of the 7-14
      proteins, two proteins of 95 and 51 kD molecular identities were phosphorylated
      at tyrosine residues. Treatment with Talpha1 enhanced and anti-FA-1 monoclonal
      antibody completely blocked phosphorylation of all the relevant proteins. Sperm
      proteins belonging to four molecular regions, namely 95 kD (double band), 63 kD
      (one band), 51 kD (one band) and 14-18 kD (three bands) were involved in ZP
      binding. Three of these, namely 95 kD, 51 kD and 14-18 kD proteins demonstrated
      the presence of tyrosine phosphorylation, and the 51 kD protein (that is FA-1
      antigen) also showed autophosphorylating activity. These findings, along with the
      other available data, indicate a vital role of protein tyrosine phosphorylation
      in sperm capacitation, acrosomal exocytosis and zona pellucida binding in humans.
      Since tyrosine phosphorylation is a primary/even exclusive indication of signal
      transduction, it appears that a signal transduction pathway is involved in
      fertilizability of human sperm.

PMID- 9159229
TI  - Molecular biology of the GABA(A) receptor: functional domains implicated by
      mutational analysis.
AB  - GABA(A) receptors are the major inhibitory neurotransmitter receptors in
      mammalian brain. They belong to a family of ligand-gated ion channels that also
      includes the nicotinic acetylcholine receptors, glycine receptors and 5HT(3)
      receptors. Each receptor in the family is believed to be a pentamer of homologous
      subunits that assemble to form a central transmembrane ion pore which, in the
      case of the GABA(A) receptor, is anion-selective. For almost twenty years, there
      has been tremendous interest in the structure and function of GABA(A) receptors,
      not only because of their importance in regulating brain excitability but also
      because these proteins are the specific targets for a wide variety of therapeutic
      agents including the anxiolytic benzodiazepines and barbiturates. Molecular
      cloning has revealed that GABA(A) receptors are heterogeneous, being formed by
      combinations of different isoforms of several subunit classes (alpha, beta,
      gamma, delta). The physiological and pharmacological properties of individual
      GABAA receptor subtypes appear to depend on their precise subunit complement. In
      this review, we focus on the application of modern techniques in molecular
      biology, particularly mutational analysis, to identify structural domains of
      these receptors that are important for ligand recognition and receptor function.

PMID- 9159230
TI  - The cAMP-dependent kinase pathway and human sperm acrosomal exocytosis.
AB  - The human sperm acrosome reaction (AR) appears to be analogous to various somatic
      cell exocytotic events. The AR can be induced in vitro by naturally occurring and
      synthetic compounds, such as, human periovulatory follicular fluid (hFF) and
      calcium ionophore A23187. The events that culminate in the AR appear to involve
      at least two second messenger pathways. One pathway involves the generation of
      the second messenger adenosine 3':5'-cyclic monophosphate (cAMP) by the
      amplifying enzyme adenylate cyclase and leading to the activation of cAMP
      dependent kinase (PKA). The effect of PKA stimulators, such as, forskolin and
      cAMP analogues, on AR was tested and they were found to stimulate the AR.
      Inhibitors of specific components in the PKA pathway, e.g. adenosine analogues
      and PKA inhibitors, induced dose-dependent reductions in the AR. Furthermore,
      naturally occurring agonists, including, hFF and solubilized human zona pellucida
      (sZP), in combination with PKA inhibitors, led to a significantly lower AR.
      Collectively, these data provide strong support for the role of the PKA pathway
      in the AR.

PMID- 9159231
TI  - Herpes simplex virus: a tool for neuroscientists.
AB  - Herpes viruses have received a great deal of attention due to their widespread
      and ubiquitous prevalence in the human population and to the diverse range of
      diseases caused as a result of an infection. During the last 20-25 years, many
      research laboratories have investigated the pathogenesis and molecular biology of
      these viruses; particularly herpes simplex virus (HSV). As a result of this
      research, HSV has begun to get the attention of neuroscientists. In fact, in the
      last few years there has been an explosion of research involving the use of HSV
      and related viruses as tools or model systems for different areas of neuroscience
      research. This brief review will describe several of these areas including
      demyelinating diseases, neuronal tracings, and genetic therapy.

PMID- 9159232
TI  - Xenotransplantation--state of the art.
AB  - Organ transplantation is limited by the number of cadaveric human donor organs
      that become available. Xenotransplantation--the transplantation of organs and
      tissues between animal species--would supply an unlimited number of organs and
      offer many other advantages. The pig has been identified as the most suitable
      donor animal. Pig organs, when transplanted into humans or nonhuman primates,
      are, however, rejected hyperacutely within minutes by antibody-mediated
      complement activation. Human anti-pig antibodies have been identified as being
      directed against Gal alpha1-3galactose epitopes on pig vascular endothelium.
      Major efforts are being made to overcome this hyperacute rejection. Methods being
      investigated include (i) depletion or inhibition of recipient antibodies or
      complement, (ii) development of transgenic pigs that do not express the alphaGal
      epitope and/or express a human complement inhibiting protein (e.g. DAF), and
      (iii) development of immunological tolerance to pig organs in the recipient. If
      complement activation is prevented, e.g. by inhibition of complement activation
      by cobra venom factor, soluble complement receptor 1 or by the use of hDAF
      transgenic pig organs, then "delayed xenograft rejection" occurs and is again
      believed to be largely antibody-dependent. Experimental pig-to-primate organ
      xenotransplantation is now, however, resulting in transplant function for days
      and weeks rather than minutes, and there is therefore optimism that we are on the
      threshold of a new era in the field of the transplantation of vital organs.

PMID- 9159233
TI  - CREM: a transcriptional master switch during the spermatogenesis differentiation
      program.
AB  - Spermatogenesis is a complex differentiation process under the hormonal control
      of the hypothalamic-pituitary axis. The CREM gene encodes activators and
      repressors of cAMP-mediated gene transcription. The transcript corresponding to
      the activator isoform CREMtau is found at high levels in pachytene spermatocytes
      onwards. The CREMtau protein, however, is present only in post-meiotic spermatids
      where it activates the transcription of testis-specific genes, such as the
      protamines and transition proteins. Mice in which the CREM gene has been
      inactivated by homologous recombination have been generated. Homozygous male
      mutant mice are sterile and produce no spermatozoa. Histological analysis of the
      seminiferous tubules reveal a complete arrest of spermatogenesis at the first
      step of spermiogenesis. CREM deficiency results in the lack of post-meiotic gene
      expression and a ten-fold increase in apoptotic germ cells. These results
      demonstrate the essential role of CREM in spermatogenesis and are reminiscent of
      some cases of male infertility.

PMID- 9159234
TI  - Structure-function relationship in the IL-1 family.
AB  - The interleukin 1 (IL-1) family is a group of related cytokines including two
      agonist proteins (IL-1alpha and IL-1beta), each derived by enzymatic cleavage of
      precursor proteins (pro-IL-1alpha and pro-IL-1beta), and three forms of an
      antagonist protein (IL-1ra, icIL-1raI, icIL-1raII). IL-1 plays a key role in the
      onset and development of the host reaction to invasion, being an important factor
      in the initiation of the inflammatory response and in the triggering of immune
      functions. Due to its pleiotropic activity and to the high potency of its
      inflammatory effects, IL-1 activity is tightly regulated in the body by a complex
      network of control systems. These include the presence of two types of
      inhibitors, the receptor antagonist IL-1ra and the second type of IL-1 receptor
      (IL-1RI), which is a natural scavenger of IL-1. Furthermore, regulation of IL-1
      activity is attained by a strict hierarchy of binding affinity of the two
      receptors (the activating IL-1RI and the inhibitory IL-1RII) for the various
      members of the IL-1 family. Additional levels of control are represented by the
      presence of soluble forms of both receptors and of immature pro-IL-1 forms with
      different characteristics of activity and receptor binding capacity. To clarify
      the features of reciprocal interaction among ligands and receptors, in the
      attempt to understand the rules regulating the IL-1 system and its effectiveness,
      a deep analysis of the relationship between structure and function in the
      proteins of the IL-1 family becomes of key importance. Information on this line
      has been provided by several groups mainly with studies of mutagenesis of IL
      1alpha, IL-1beta and IL-1ra in parallel with biological assays of activity. In
      this review, a survey of the available data is provided, in order to construct a
      hypothetical model of the functional structure of IL-1 proteins as a basis for
      future therapeutic interventions based on genetic and protein engineering.

PMID- 9159235
TI  - Venous thromboembolism and cancer: a two-way clinical association.
AB  - In recent years, a growing body of evidence has provided the convincing
      demonstration of a strong association between cancer and venous thromboembolism.
      This relationship is further supported by the risk of developing overt malignancy
      in patients with idiopathic venous thromboembolism. However, the cost-to-benefit
      ratio of an extensive diagnostic work-up aimed at identifying an occult cancer in
      patients with spontaneous thromboembolism still has to be demonstrated. During
      prolonged immobilization from any cause, and following surgical interventions,
      patients with cancer are at a remarkably higher risk of venous thromboembolism
      than patients free from malignant disorders. Standard heparin in adjusted doses
      or a low-molecular-weight heparin in doses commonly recommended for high risk
      surgical patients represent the prophylactic treatment of choice for cancer
      patients undergoing an extensive abdominal or pelvic intervention. Furthermore,
      the risk of thrombotic episodes is increased in cancer patients by chemotherapy
      and by the use of indwelling central venous catheters. Recent data suggest a
      positive benefit-to-risk ratio with the systematical use of fixed mini-dose of
      warfarin in both conditions. After experiencing an episode of thrombosis, cancer
      patients remain at risk of recurrence for as long as the cancer is active.
      Therefore, they should be protected by a long-term course of oral
      anticoagulation. The risk of recurrent thrombotic events despite adequate
      anticoagulation is higher in patients with cancer than in those without cancer.
      The routine use of long-term subcutaneous heparin therapy rather than oral
      anticoagulants should be reserved for patients in whom warfarin has been
      ineffective. Can antithrombotic drugs improve survival in cancer patients? In
      cancer patients affected by deep-vein thrombosis, the treatment with low
      molecular-weight heparins has been reported to lower mortality at a higher extent
      than the standard heparin therapy. Such an observation suggests that these agents
      might develop an antineoplastic activity.

PMID- 9159236
TI  - The immune system: a look from a distance.
AB  - The self-nonself discrimination is germline encoded for defense mechanisms, but
      it is somatically learned for the immune system and this is the fundamental
      difference between the two. When referring to the defense mechanisms of
      vertebrates, immunologists like to use the term "innate immune systems" to
      describe the germline encoded class of defense mechanism. It was the acquisition
      of a somatically learned S-NS discrimination during vertebrate evolution that
      permitted the immune system to develop large recognitive repertoires compared to
      those of defense mechanisms. This seemingly boundless immune repertoire has
      fascinated immunologists for almost a century. Today we have a better
      understanding of the size and function of the antibody repertoire. Humoral
      antibody effector functions depend upon secreted immunoglobulin and the
      concentration of antibody must reach a minimum effective threshold in a short
      enough time to stop a growing pathogen before it becomes lethal. This requires
      that initially an equivalent number of B-cells per ml respond to the pathogen.
      This number of B-cells must respond for each and every milliliter of animal.
      Consequently, the humoral immune system must be iterated. This straightforward
      conclusion has far reaching implications, some of which are explored in this
      review.

PMID- 9159238
TI  - Molecular and cellular biology of interleukin-6 and its receptor.
AB  - Interleukin-6 (IL-6) is a member of the family of cytokines collectively termed
      "the interleukin-6 type cytokines." Among its many functions, IL-6 plays an
      active role in immunology, bone metabolism, reproduction, arthritis, neoplasia,
      and aging. IL-6 expression is regulated by a variety of factors, including
      steroidal hormones, at both the transcriptional and post-transcriptional levels.
      IL-6 achieves its effects through the ligand-specific IL-6 receptor (IL-6R).
      Unlike most other cytokine receptors, the IL-6R is active in both membrane bound
      and soluble forms. Defining mechanisms to control IL-6 or IL-6R expression may
      prove useful for therapy of the many clinical disorders in IL-6 plays a role.

PMID- 9159237
TI  - Invasion of human glioma: role of extracellular matrix proteins.
AB  - The invasion of glioma into normal brain tissue is a major challenge to clinical
      intervention because these tumors often highly infiltrate the surrounding brain
      tissue. Total surgical resection of gliomas is impossible, and recurrence of
      tumor growth is a common phenomenon; patients have a mean survival time of 8-12
      months. Although in recent years substantial progress has been made toward
      understanding the invasive behavior of gliomas in vitro and in vivo, the factors
      responsible for the extensive infiltration are still poorly documented. This
      review focuses on recent research concerning the invasion of gliomas, as well as
      the extracellular matrix components, and the proteolytic enzymes involved. A
      better understanding of cell-matrix interactions will help in developing
      therapeutic strategies to decrease the invasion of gliomas.

PMID- 9159240
TI  - Role of leukocytes and leukocyte adhesion molecules in renal ischemic-reperfusion
      injury.
AB  - Renal ischemic-reperfusion injury (IRI) occurs frequently in transplanted as well
      as native kidneys. Effective treatment for this process is still elusive.
      Leukocytes and their products may be important in the pathogenesis of renal IRI,
      however their role is still controversial. Recently, adhesion receptors on
      leukocytes and their corresponding ligands have been identified. In the heart,
      considerable evidence supports the role of CD11/CD18, ICAM-1, and the selectin
      receptors in IRI. However, based on experimental studies in animal models, even
      though renal IRI appears to be ICAM-1 mediated, the role of the CD11/CD18 pathway
      appears to be minimal. In addition, the available evidence does not support the
      concept that L-selectin has significant involvement in renal IRI. In this review,
      the data and controversies regarding the role of leukocytes and leukocyte
      adhesion molecules in renal IRI are discussed.

PMID- 9159239
TI  - Corticotropin releasing hormone (CRH) in normal and pregnant uterus:
      physiological implications.
AB  - Corticotropin-releasing hormone, is a hypothalamic neuropeptide, responsible not
      only for the endocrine but also the autonomic, immunological and behavioural
      responses of mammalian organisms to stress. CRH is also expressed in female
      reproductive tissues, such as placenta and uterus. Multiple sites within the
      pregnant uterine cavity express the CRH gene, including the trophoblasts, fetal
      membranes (chorion, amnion) and decidua. The trophoblastic syncytium appears to
      be the major source of placental CRH. It is postulated that placental CRH
      influences the HPA axis of either mother or fetus and participates at the
      initiation of labour. Recent findings show that human and rat uterus express the
      CRH gene. Epithelial cells of both species are the main source of endometrial
      CRH, while stroma does not seem to express it, unless it differentiates to
      decidua. Estrogens and glucocorticoids inhibit and prostaglandin E2 stimulates
      the promoter of human CRH gene in transfected human endometrial cells, suggesting
      that endometrial CRH gene expression is under the control of these agents.
      Moreover, in rats, endometrial CRH expression is significantly higher at the
      implantation sites, compared to that at the inter-implantation uterine regions.
      Given the proinflammatory/vasoregulatory properties of CRH, we hypothesize that
      endometrial CRH may participate in the regulation of intrauterine phenomena, such
      as blastocyst implantation, endometrial vascularization and myometrial
      contractility.

PMID- 9159241
TI  - Pharmacological manipulation of the complement system in human diseases.
AB  - Complement is one of the powerful effector systems involved in the body's
      defense. When present in a dormant state it can, in concert with other components
      of immune system, protect the individual from foreign pathogens. However,
      inappropriately activated complement can cause disease. Several disease states
      such as immune complex and autoimmune diseases and deficiencies of some
      complement regulators are associated with inappropriate activation of complement.
      In some diseases complement is activated for a long or indefinite period while in
      others for a comparatively short time; in some it is activated systemically, in
      others locally; in some whole cascade is activated, in others only a few
      components are activated; in some classical pathway is activated, in others
      alternative pathway. In some diseases activation of complement takes place on
      cell and tissue surfaces. In many complement activating diseases biological
      activities of complement fragments become detrimental resulting in tissue injury
      and disease. Inhibition of complement by specific inhibitors is likely to arrest
      complement mediated disease processes. From this point of view, some laboratories
      are developing low molecular weight synthetic inhibitors whereas others are
      focusing on the development of high molecular weight plasma or cell surface
      complement inhibitors in their natural or recombinant forms for therapeutic
      purposes. A review concerning development of low molecular weight inhibitors with
      the eventual aim of manipulating complement system in human diseases was recently
      published (1,2). This review is concerned with high molecular weight natural or
      recombinant complement inhibitory molecules in human plasma or cell membranes,
      some of which are already in clinical use.

PMID- 9159242
TI  - Therapeutic application of intravenous human natural immunoglobulin preparation.
AB  - Human natural immunoglobulin (HunIg) preparation for intravenous use has been
      used in various diseases. The most typical application of this preparation is
      agammaglobulinemia. Currently, however, this preparation is being used in the
      therapy of many other disorders. These include thrombocytopenia, Kawasaki
      disease, systemic vasculitis, several other disorders of autoimmune origin and
      systemic inflammation such as sepsis. In some diseases, the clinical improvement
      following use of HunIg has been dramatic, while in others its effect is not
      striking. Due to rarity of the side effects, the range of application of HunIg
      has been recently broadened. Such side effects include transmission of several
      diseases such as hepatitis and retroviral infections. Before it is recommended
      for use, however, and primarily due to expense, the efficacy of this drug should
      be carefully evaluated. The mechanism of action of HunIg is not fully understood.
      However, it has been suggested that its action may involve blockade of Fc
      receptor, an anti-cytokine effect, or inhibition of complement activation. In
      this review, the mechanism of action of HunIgG and its application in human
      diseases are discussed.

PMID- 9159243
TI  - Pig alpha1, 3galactosyltransferase: a major target for genetic manipulation in
      xenotransplantation.
AB  - Terminal carbohydrate residues of glycolipids and glycoproteins display
      polymorphism among as well as within various species. With the exception of Old
      World monkeys, great apes and man, the Gala1,3Gal structure is widely expressed
      in all mammals examined so far. The lack of expression of the glycosyltransferase
      responsible for the synthesis of Gala1,3Gal leads to the production of high
      titers of natural antibodies (NAb) against the Gala1,3Gal of other species. The
      inactivation of this gene occurred during early evolution of primates.
      Neutralization of viruses (e.g. retroviruses) carrying the epitope, by the pre
      formed human NAb, indicates one possible evolutionary reason for the polymorphism
      of terminal carbohydrates among as well as within species. It has been shown that
      this epitope constitutes the major target, on pig endothelial cells (EC), for the
      pre-formed human NAb resulting in a hyperacute rejection (HAR) response. This
      currently makes transplantation of e.g. pig organs to humans impossible. Efforts
      are currently underway to prevent or to eradicate the expression of this epitope
      in transgenic pigs. Such pigs are likely to display a greatly increased
      resistance to the HAR.

PMID- 9159244
TI  - Mycoplasmas and HIV infection: from epidemiology to their interaction with immune
      cells.
AB  - Mycoplasmas are possible HIV cofactors, contributing to the evolution of AIDS.
      Our knowledge about mycoplasma prevalence in HIV-infected subjects has
      considerably increased due the development of specific detection assays. A new
      mycoplasma, Mycoplasma penetrans, has been identified and has been shown to be
      associated with HIV infection, at least among individuals with homosexual
      practices. We and others investigated the properties of M. fermentans and M.
      penetrans concerning cell colonization, cell invasion and cytopathogenicity. The
      molecular components which are involved in the interaction between these bacteria
      and immune cells are beginning to be identified and characterized. Membrane
      lipoproteins of these wall-less prokaryotes are key components in their
      interaction with B cells and surface capsular material may contribute to their
      defense from the host immune response.

PMID- 9159245
TI  - Immunoglobulin therapy in Kawasaki syndrome and RSV prophylaxis.
AB  - Kawasaki syndrome and RSV infection are common illnesses that afflict infants and
      young children. Recent studies demonstrate that intravenous immunoglobulin (IVIG)
      treatment significantly reduces the clinical severity of these illnesses. The
      purpose of the current review will be initially to examine mechanisms of disease
      pathogenesis in KS and RSV infection. This will be followed by a discussion of
      the potential mechanisms by which IVIG acts in these two illnesses. In both KS
      and RSV prophylaxis, an important action by which IVIG may work is primarily
      through toxin or microbial neutralization resulting in the dampening or
      prevention of the inflammatory response. Other immunomodulatory actions of IVIG
      are likely to be operative in these diseases and will be an active area of future
      research.

PMID- 9159247
TI  - Application of molecular biology-based methods to the diagnosis of infectious
      diseases.
AB  - The basis for effective treatment and cure of a patient is the rapid diagnosis of
      the disease and its causative agent, which is founded on the analysis of the
      clinical symptoms coupled with laboratory tests. As we approach the 21st century,
      clinicians are becoming increasingly able to diagnose and treat diseases at the
      molecular level. The rapid development of new methods and techniques in the area
      of molecular biology has gained new insights into the genetic and structural
      features of a considerable number of human pathogens. These results obtained by
      intensive basic research are currently leading to improved diagnostic procedures.
      Basically, there are four different possibilities for laboratory diagnosis of
      infections: 1. direct detection of the pathogens (e.g., microscopy and/or
      culture), 2. detection of protein components of the pathogens with the help of
      specific antibodies (e.g., antigen capture ELISA) 3. IgA-, IgM- and IgG-specific
      detection of antibodies directed against a given pathogen and changes in their
      corresponding titer, and as the most sensitive method, 4. specific detection of
      nucleic acids (e.g., PCR) of the pathogens. Here, the human immunodeficiency
      virus (HIV) and Mycobacterium tuberculosis are serving as examples to review the
      recent developments as well as the future perspectives in molecular biology-based
      laboratory diagnosis.

PMID- 9159246
TI  - Methods for enhancement of sperm function.
AB  - From a review of recent advances in human reproduction, it is apparent that
      therapeutic approaches to male infertility have been revolutionized. While our
      understanding of sperm function at the molecular level is steadily increasing,
      the realization of consistent oocyte fertilization by mechanically bypassing
      natural barriers has given new perspective for future investigation. This chapter
      reviews current knowledge of adjuvants that enhance sperm function and lend
      themselves to clinical application. Each compound is presented with recent
      publications supporting proposed mechanisms of action. Specifically, follicular
      fluid, progesterone, pentoxifylline, platelet activating factor and other
      cytokines have been studied for their impact on the in vitro fertilization
      capacity of spermatozoa. Intracytoplasmic sperm injection (ICSI) has provided
      infertile couples with hope for successful reproduction without sperm donation.
      The precise mechanism that allows subsequent pronuclear formation and syngamy is
      currently unknown and experimental models are few. Adjuvants that can be used in
      conjunction with controlled ovarian stimulation and intrauterine insemination are
      prominent areas for further research as this would provide an alternative to the
      expense and risks of in vitro fertilization and embryo transfer.

PMID- 9159248
TI  - Oxidative stress and role of antioxidants in normal and abnormal sperm function.
AB  - Defective sperm function is the most common cause of infertility, and until
      recently, it was difficult to evaluate and treat. Part of this difficulty was due
      to our incomplete understanding of the factors contributing to normal and
      abnormal sperm function leading to male infertility. Mammalian spermatozoa
      membranes are rich in high unsaturated fatty acids and are sensitive to oxygen
      induced damage mediated by lipid peroxidation. Limited endogenous mechanisms
      exist to reverse these damages. The excessive generation of reactive oxygen
      species (ROS) by abnormal spermatozoa and by contaminating leukocytes
      (leukocytospermia) has been identified as one of the few defined etiologies for
      male infertility. In a normal situation, the seminal plasma contains antioxidant
      mechanisms which are likely to quench these ROS and protect against any likely
      damage to spermatozoa. However, during genitourinary infection/inflammation these
      antioxidant mechanisms may downplay and create a situation called oxidative
      stress. In addition, aging and environmental toxicants are also likely to further
      induce this oxidative stress. Assessment of such oxidative stress status (OSS)
      may help in the medical treatment of this male factor infertility by suitable
      antioxidants.

PMID- 9159249
TI  - Application of sperm antigens in immunocontraception.
AB  - Development of a vaccine(s) based on sperm antigens represents a promising
      approach for contraception. The utility of an antigen in immunocontraception is
      contingent upon its tissue specificity, involvement in human fertility, and
      immunogenicity. A number of antigens have been characterized from the sperm
      surface. Notable among these are LDH-C4, RSA antigens, PH-20, SP 1U, HSA-63, FA
      1, FA-2 and CS-1. These antigens have been proposed as potential candidates for
      the development of contraceptive vaccine(s). Their current status, application,
      relative merits, and immunogenicity in immunocontraception are discussed in this
      review.

PMID- 9159250
TI  - Assessment of sperm function and clinical aspects of impaired sperm function.
AB  - Fertility is dependent on a complex set of events, involving both male and female
      components. Normal sperm function involves many steps, including motility,
      capacitation, acrosome reactivity and, ultimately, fertilization of the oocyte.
      While male fertility is most often assessed by means of gross semen parameters,
      infertility may also be caused by abnormal sperm function, and only by performing
      specific tests of this function, may the reasons for infertility become evident.
      Specific tests which may be helpful include semen analysis, detailed sperm
      motility assessment, motility longevity, hypo-osmotic swelling test, mucus
      penetration assay, acrosome reactivity, antisperm antibody tests, sperm
      penetration assay and in vitro fertilization. Relatively well-defined syndromes
      of abnormal sperm function include immunologic infertility, immotile-cilia
      syndrome, anejaculation and nifedpine-associated infertility.

PMID- 9159251
TI  - Sonohysterographic imaging of the endometrial cavity.
AB  - Vaginal ultrasound is the most effective method of imaging the contents of the
      true pelvis in the female. Saline influsion sonohysterography (SIS) is a simple
      refinement of the standard vaginal sonographic exam. Here, we briefly describe
      and demonstrate our use of this latter technique.

PMID- 9159252
TI  - Intracytoplasmic sperm injection (ICSI).

PMID- 9159253
TI  - Virtual reality publication of spiral ct-derived three-dimensional models: or,
      creation of spiral, CT-derived, three-dimensional VRML objects.
AB  - Three-dimensional models can be generated from slice images, such as those
      obtained from computed tomography (CT) and magnetic resonance imaging (MRI) using
      a variety of techniques. A popular method for rendering 3D anatomical models is
      the creation of polygonal mesh surfaces representing the boundary between
      tissues. Mesh surfaces can be rendered extremely quickly using conventional
      personal computers, without recourse to more expensive graphic workstations. The
      dissemination of three-dimensional (3D) models across the Internet has been made
      significantly easier by the definition of the Virtual Reality Markup Language
      (VRML) format. The VRML definition allows the parameters and relationships of 3D
      objects to be described in a text format. The text file can be transfered from a
      host computer to a remote client computer through the World Wide Web and viewed
      using readily available software (See Appendix). VRML is based on the definition
      of primitive 3D objects such as polygons and spheres. Consequently, the
      transition from a mesh surface derived from a clinical image data set to a VRML
      object is relatively simple, allowing for convenient and cost-effective
      dissemination of 3D clinical models across the internet.

PMID- 9159254
TI  - The role of laparoscopy in the diagnosis of gynecologic pathologies.

PMID- 9159255
TI  - The role of laser in the laparoscopic treatment of gynecologic pathologies.

PMID- 9159256
TI  - Place and modalities of laparoscopy in surgical management of suspected adnexal
      masses.
AB  - Only benign adnexal masses are suitable for treatment by operative laparoscopy.
      Ovarian cancer must always be managed by midline laparotomy. In our experience
      the preoperative workup (clinical examination, study of past history, trans
      vaginal ultrasonography, doppler, tumoral markers etc.) together with the
      diagnostic phase of laparoscopy provide a sensitivity value of 100%, a positive
      predictive value of 50% and a negative predictive value of 100% for diagnosis of
      malignancy. Provided a strict selection, laparoscopy is reliable both for the
      diagnosis and the management of benign ovarian masses.

PMID- 9159257
TI  - Benign ovarian tumors.
AB  - The aim of this study was to analyze whether, in a series of benign ovarian
      tumors, the diagnosis could be reliably established and whether the surgical
      treatment was appropriate. All patients underwent the preoperative evaluation and
      laparotomy was performed in all cases. The patients were followed for up to 3-8
      years after surgery. Demolition surgery (mono or bilateral adnexiectomy with
      hysterectomy) was more frequently performed in postmenopausal women, while
      conservative surgery (enucleation, monolateral adnexiectomy) was done in fertile
      women. Evaluation of the treatment in our series shows that the surgical approach
      was more aggressive than necessary with respect to the histological diagnosis.
      Although in the serous and mucinous form tumors on can not rule out the
      possibility of malignancy in the remaining part of the ovary, the current
      approach should be more conservative, with enucleation of the mass and
      preservation of the ovary.

PMID- 9159258
TI  - Management of benign adnexal masses by vaginal route.
AB  - Until recently, surgical treatment of a benign adnexal mass implied a laparotomy.
      In recent years, the development of laparoscopic surgery, as well as ultrasound
      guided aspiration techniques, have significantly modified the treatment options
      for these patients. These procedures have shown considerable advantages. They
      have reduced surgical trauma and have shortened the hospital stay. We present the
      results of our experience on the feasibility of a trans-vaginal surgical approach
      for the removal of benign adnexal masses. This technique, using traditional and
      cheap surgical instruments, allows the surgeon to excise benign adnexal masses,
      by entering the peritoneum through the posterior vaginal fornix and thus avoids
      the trauma of laparotomy. Fifty-four patients were operated on by this technique
      at our Department. The mean age was 39 years (range 21-66). In all cases, the
      operation was completed by the trans-vaginal approach. The median operative time
      was 30 minutes (range 20-45), and no blood transfusion was needed. The
      pathological diagnoses were as follows: functional ovarian cyst; 19,
      endometriotic cyst; 18, dermoid cyst; 11, parovarian cyst; 4 and peduncolated
      fibroid of the uterine fundus; 2 cases. The diameter of the adnexal masses ranged
      from 3 to 10 cm (median of 6 cm). In 30 cases, a conservative surgery was done
      (including 2 myomectomies), whereas in 24 cases, the adnexectomy was needed.
      Median post-operative stay in hospital was 4 days (range 1-14). This study shows
      the feasibility of trans-vaginal surgical approach for benign adnexal masses. The
      advantages and limitations of this technique, as well as of the traditional and
      laparoscopic surgery are considered and discussed. We believe that the
      transvaginal approach could be useful and cost-effective for the treatment of
      selected cases of adnexal masses.

PMID- 9159259
TI  - Ovarian cancer: natural history and metastatic pattern.
AB  - Ovarian cancer begins at a molecular level, however to date, our knowledge of
      genetic changes and mechanisms of ovarian tumorigenesis is limited. The natural
      history of ovarian cancer may depend on different anatomo-clinical and biological
      factors. In the life history of ovarian cancers the stage, histology, tumor
      grade, age of the patient and gene abnormalities, both oncogenes (c-myc, H-ra,
      new) and oncosuppressor genes (p53, in particular), DNA ploidy and steroid
      receptor status have important prognostic significance. Residual disease, when
      less than 1 cm, is another important prognostic factor, being significantly
      associated to the survival and, progression free, improvement in the survival. In
      the low stage ovarian cancer (Stage IA, IB, IAII,IBII,IC,IIA,IIB,IIC), adjuvant
      treatment seems not to influence Disease Free Survival (DFS) or Overall Survival
      (OS) The exception to this rule is when cisplatin regimen is assessed, as it can
      highly reduce the relapse rate while the survival is not significantly
      influenced. Ovarian cancers disseminate, primarily by continuity. Lymphatic
      dissemination to the pelvic and para-aortic lymph nodes (40% of patients at stage
      III-IV disease) as well as to the peritoneum is common. At the time of diagnosis,
      bone or brain metastases are rarely present and their presence is not related to
      the histology or grading of the tumor.

PMID- 9159260
TI  - Treatment strategies of the borderline ovarian tumors.
AB  - The present study was undertaken to establish the role of surgical procedures,
      histologic type, and stage of the tumor on the survival rate of patients with
      borderline ovarian tumors in a 5 to 15 years of follow-up. Data reported in the
      literature have shown the low malignancy of this cancer and that only the stage,
      but not the pathological diagnosis, is significantly influencing the survival
      rate of the patients. After 5 years, the survival rate of patients with tumors of
      stage I to stage II is 98.2% (n=567) and 81.4% (n=46), respectively, with no
      statistical difference. After 5 years, survival rate between tumors of stage I to
      stage III is 98.2% (n=567) and 79.1% (n=96), respectively (p< 0.05). The data
      shows that for borderline ovarian tumors, a minimally invasive surgery is
      warranted.

PMID- 9159261
TI  - Potential role of growth factors in ovarian cancer.
AB  - As with many other tumors, the origin and development of ovarian cancer is
      constituted by several molecular mechanisms, many of which are still unknown.
      Furthermore, data in the literature are incomplete and often contradictory, and
      they are mainly founded on results obtained on cell lines and not on observations
      based on the in vivo study of ovarian cancer. Despite this situation, the study
      of control mechanisms of proliferation and differentiation in normal ovarian
      functioning has enabled clinicians to identify certain growth factors and
      oncogenes which seem to have an important role in the neoplastic transformation
      of ovarian tissue. In this review, our aim is to summarise the most important
      data regarding function of growth factors and oncogene in normal and neoplastic
      epithelial ovarian cells.

PMID- 9159262
TI  - Chemotherapy of advanced ovarian cancer.
AB  - Majority of ovarian cancer patients have advanced disease (stage III or IV) at
      diagnosis and the prognosis of these patients is poor in spite of aggressive
      surgery. Therefore chemotherapy has gained a fundamental role in the therapeutic
      approach of ovarian cancer. Platinum compounds in combination with alkylating
      agents and taxoids have the higher antitumor activity in ovarian cancer, while
      the role of anthracyclines remains controversial. Our 10-year experience with
      cisplatinum-based polychemotherapy in 196 advanced ovarian cancer patients
      previously untreated with chemotherapy is reported. 74 patients were treated with
      the combination cis-platinum and anthracyclines; 53 patients received the
      combination cis-platinum plus epirubicin alternated to cyclophosphamide plus 5
      fluorouracil; 48 patients were treated with cis-platinum plus cyclophosphamide
      plus epirubicin and 21 patients were treated with the same combination with
      intraperitoneal administration of cisplatin. Our data confirm literature results
      of 55% remission rate, with 29% showing complete remissions. The median survival
      was 79 weeks and the overall 10-year survival was 13%. Complete responders had a
      median survival of 263 weeks and a 30% survival at 10 years. The main prognostic
      factors in our retrospective analysis were the objective remission, the size of
      residual tumor, the performance status and the stage. With the combination
      carboplatin (300-400 mg/sm) and cyclophosphamide (600 mg/sm) we observed 80%
      objective responses (23% complete responses) in 53 advanced ovarian cancer
      patients. The median overall survival in this group was 140 weeks. We carried out
      a phase II, non-randomized study of taxol in 54 ovarian cancer patients
      pretreated with platinum-compounds. The overall tolerability was good and an
      objective remission was observed in 47% of cases (8% complete remissions). The
      median survival was 68 weeks. As a consequence of our previous experience, a
      phase I dose-finding study with the combination carboplatin and taxol was started
      in our Division in 1994. Up to now, 22 chemotherapy untreated patients entered
      the study and the 5th dose level (taxol 175 mg/sm and carboplatin 350 mg/sm) has
      been completed without reaching the maximum tolerated dose. Our preliminary data
      suggest that the combination taxol-carboplatin is very active as the first-line
      chemotherapy in advanced ovarian cancer (73% objective remissions in 15 evaluated
      patients).

PMID- 9159263
TI  - Pregnancy status and feedlot performance of beef heifers actively immunized
      against gonadotropin-releasing hormone.
AB  - The contraceptive effect of active immunization against GnRH was evaluated in
      beef heifers. Crossbred heifers were randomized by breed and weight (initial
      weight = 227.3 +/- 1.2 kg) and assigned to one of three treatment groups. Animals
      in Group IB (n = 48) were actively immunized against GnRH; heifers in Groups NB
      (n = 48) and NN (n = 49) did not receive the anti-GnRH vaccine. Sixteen weeks
      after primary immunization, bulls of proven fertility were introduced into pens
      containing Groups IB and NB. Bulls were maintained with heifers for 2 mo. Heifers
      in group NN were not intentionally exposed to fertile males. At the end of the
      breeding period, heifers received Synovex H implants and entered a commercial
      feedlot. Heifers were slaughtered after 116 d of feedlot confinement. Anti-GnRH
      titer was evident in all heifers (48 of 48) immunized against GnRH. Gravid uteri
      were present at slaughter in 40 of 48 (83.3%) NB heifers. In contrast, only four
      (8.3%) IB and two (4.1%) NN heifers carried gravid uteri at slaughter. Although
      ADG did not differ between groups during feedlot confinement, ADG during the
      breeding period was higher (P < .05) in IB heifers than in NN control animals.
      Dressing percentage and longissimus muscle area were decreased (P < .05) and
      marbling and quality grade were increased (P < .05) in NB heifers compared with
      NN control heifers. Carcass traits of IB heifers were intermediate between those
      of the NB and NN groups. Taken together, these data indicate that active
      immunization against GnRH reduces the fertility of terminal heifers. These
      observations suggest that immunoneutralization of GnRH may be an effective
      management tool that will reduce the incidence of unintended pregnancy in heifers
      destined for feedlots.

PMID- 9159264
TI  - Late-gestation treatment of pregnant cows with trenbolone acetate does not
      increase subsequent growth of heifer calves.
AB  - Fifty crossbred cows (38 multiparous and 12 nulliparous) were used to evaluate in
      utero androgenization of heifer calves with trenbolone acetate. Three 200-mg
      trenbolone acetate (Finaplix-H) implants were implanted in the ear of treated
      cows (n = 24) on d 214 +/- 11 of gestation; the remaining animals (n = 26) were
      used as controls. Cows' rate of gain, serum levels of trenbolone acetate,
      gestation length, degree of dystocia, percentage bred back, days until
      conception, and 24-h milk production were evaluated. Fourteen-day weigh periods
      until parturition indicated that trenbolone acetate-treated dams had an increased
      (P < .05) average daily gain (1.05 +/- .1 kg) compared with control cows (.55 +/-
      .1 kg). Serum concentrations of trenbolone acetate were higher (P < .01) in
      treated cows with a peak at 9 d after implantation and returned to basal
      concentrations by d 77. Treatment did not affect degree of dystocia among all
      cows (P > .05) but seemed to increase (P < .01) the incidence of dystocia in
      nulliparous cows compared with nulliparous control cows. Gestation length and
      subsequent fertility were not affected by treatment (P > .05). Similarly, there
      was no difference in 24-h milk production (P > .05) between treated and control
      cows. Calf birth weight, phenotypic measurements at birth, vigor, average daily
      gain, carcass characteristics, and heifer reproductive tract and ovarian weights
      did not differ with treatment (P > .05). These data showed that late-gestation
      treatment with 600 mg of trenbolone acetate significantly increased weight gain
      of dams without demonstrating any androgenizing effects on the growth or physical
      characteristics of heifer calves.

PMID- 9159265
TI  - Performance, carcass, and palatability traits for cull cows fed high-energy
      concentrate diets for 0, 14, 28, 42, or 56 days.
AB  - Cull cows, thin to moderate in initial condition scores, were randomly assigned
      within breed to slaughter groups and fed a high-concentrate diet for 0, 14, 28,
      42 or 56 d (n = 40). Carcass data were collected, and one side of each carcass
      was fabricated into boneless subprimals, lean trimmings, fat, and bone. Live and
      carcass weights, ADG, and dressing percentage increased through 28 d of feeding
      (P < .05), and lean firmness increased (P < .05) through 42 d of feeding.
      Adjusted preliminary yield grades and final yield grades increased (P < .05) with
      feeding, but not to levels requiring knife trimming of fat. Fat color became
      whiter (P < .05) but marbling was not affected (P > .05) by feeding. Weights of
      fat-free lean, fat, and bone and percentages of fat in soft tissues of cow
      carcasses increased (P < .05) by 28 d on feed. Overall steak tenderness was
      higher (P < .05) for cows fed 56 d than for cows fed 0 or 14 d. Warner-Bratzler
      shear force was not affected by feeding. Amounts of soluble collagen increased (P
      < .05) in the longissimus muscle between 0 and 28 d on feed, and total collagen
      decreased (P < .05) in the biceps femoris muscle between 0 and 42 d on feed.
      Continental European cow carcasses yielded more fat-free lean and less fat (P <
      .05) and dairy cows generally provided the most tender product across all
      slaughter periods. In general, sensory tenderness and yields of cow carcass
      components increased without requiring excessive trimming of fat by feeding cull
      beef and dairy cows for periods up to 56 d.

PMID- 9159266
TI  - Estimation of direct and maternal breed effects for prediction of expected
      progeny differences for birth and weaning weights in three multibreed
      populations.
AB  - Direct and maternal breed effects on birth and 200-d weights were estimated for
      nine parental breeds (Hereford [H], Angus [A], Braunvieh [B], Limousin [L],
      Charolais [C], Simmental [S], Gelbvieh [G], Red Poll [R], and Pinzgauer [P]) that
      contributed to three composite populations (MARC I = 1/4B, 1/4C, 1/4L, 1/8H,
      1/8A; MARC II = 1/4G, 1/4S, 1/4H, 1/4A; and MARC III = 1/4R, 1/4P, 1/4H, 1/4A).
      Records from each population, the composite plus pure breeds and crosses used to
      create each composite, were analyzed separately. The animal model included fixed
      effects of contemporary group (birth year-sex-dam age), proportions of individual
      and maternal heterosis and breed inheritance as covariates, and random effects of
      additive direct genetic (a) and additive maternal genetic (m) with covariance
      (a,m), permanent environment, and residual. Sampling correlations among estimates
      of genetic fixed effects were large, especially between direct and maternal
      heterosis and between direct and maternal breed genetic effects for the same
      breed, which were close to -1. This resulted in some large estimates with
      opposite sign and large standard errors for direct and maternal breed genetic
      effects. Data from a diallel experiment with H, A, B, and R breeds, from grading
      up and from a top cross experiment were required to separate breed effects
      satisfactorily into direct and maternal genetic effects. Results indicate that
      estimation of direct and maternal breed effects needed to predict hybrid EPD for
      multibreed populations from field data may not be possible. Information from
      designed crossbreeding experiments will need to be incorporated in some way.

PMID- 9159267
TI  - Genetic and environmental parameters for ovulation rate, twinning rate, and
      weight traits in a cattle population selected for twinning.
AB  - A project was implemented in 1981 with the objective of increasing twinning rate
      in cattle. Daughters of foundation sires had twin calves at a frequency of from 8
      to 13%, and foundation females had twin calves at an average frequency of 50%.
      Data were analyzed on twinning rate, ovulation rate, and weight traits. The h2 of
      ovulation rate increased from .11 to .38 for a single estrous cycle to the mean
      of eight estrous cycles. From all data, h2 for single observation of ovulation
      rate and twinning rate were .10 and .09, respectively. The r(g) between them was
      .75. The h2 of weight traits ranged from .42 to .54 when weight traits were
      analyzed pair-wise with ovulation rate and with twinning rate. The r(g) between
      weight traits with ovulation rate ranged from .15 to .30 and with twinning rate
      ranged from .24 to .39. Phenotypic mean twinning rate increased from 1.07 to 1.29
      calves per parturition for females born 1981 through 1993, and adjusted mean
      predicted breeding value (PBV) increased from 1.07 to 1.33 calves per
      parturition. Phenotypic mean ovulation rate for fall of 1984 through fall 1994
      birth groups increased from 1.11 to 1.26 per estrous cycle, and adjusted mean PBV
      for ovulation rate increased from 1.11 to 1.29 per estrous cycle. Because of the
      high r(g) (i.e., .75) between ovulation rate and twinning rate, and because of a
      h2 of .35 for ovulation rate for the mean of six estrous cycles, repeated records
      of ovulation rate in puberal heifers is an effective indirect selection criterion
      for twinning rate. The positive r(g) between growth traits and ovulation and
      twinning rate suggest the need for some compromise when the selection goal is
      increased twinning rate with no increase in growth and size.

PMID- 9159268
TI  - The role of nursing frequency in milk production in domestic pigs.
AB  - We conducted three experiments to assess how nursing frequency affects milk
      output in early pig lactation. In Exp. 1, nursing behavior of 12 individually
      penned sows was recorded on d 1 through 3 postpartum. The milk output was
      measured using the weigh-suckle-weigh method. The spontaneous changes in the
      nursing frequency between d 1 and 2 were positively correlated with the changes
      in milk output (rS = .64), and the same was true for changes between d 2 and 3
      (rS = .77). In Exp. 2, we forced sows, 7 to 8 d after parturition, to nurse every
      35 min (10 sows) or every 70 min (eight sows) for 24 h. Sows nursing at short
      intervals had more nursings without milk ejection, but they gave 27% more milk
      and their litters gained 44% more weight during the experimental 24 h than sows
      nursing at long intervals. Litters nursed at long intervals massaged the udder
      longer after milk ejection. In Exp. 3, milk output was measured after intervals
      of 35, 50, and 70 min imposed in varied order on 11 experimental sows in the
      second week of lactation. In a separate recording of two 50-min nursings, we
      measured milk output from teats that were, or were not, sucked at the first
      nursing (i.e., giving within-sow comparison of 50 or 100 min). The milk output
      after 35, 70, and 100 min did not differ from that after 50 min, although there
      was a tendency for a slight increase with longer intervals. The results suggest
      that glands are refilled early after milk ejection and that the increase in milk
      available with prolonged intervals is only slight. As a result, it is the nursing
      frequency that plays a crucial role in adjusting the milk output.

PMID- 9159269
TI  - Visceral organ mass and cellularity in growth-restricted and refed beef steers.
AB  - Beef steers were fed in two phases to compare the effects of diet and intake on
      growth and cellularity of visceral organs. During the growing phase (237 to 327
      kg), steers were fed either a high (C) or low (F) concentrate diet. Diet F was
      available ad libitum (FA), whereas diet C was available either ad libitum (CA) or
      on a limited basis (CL) to match live weight gains of the FA group. During the
      finishing phase (327 to 481 kg), all steers received diet C either ad libitum (CA
      CA, CL-CA, and FA-CA) or restricted (CL-CL and FA-CL) to 70% of the intakes of
      corresponding CA steers. Marked nutritional effects on liver growth (e.g., -25
      and -15% in CL and FA, respectively, relative to CA) were due mainly to changes
      in cell size (i.e., protein:DNA), with smaller changes in cell numbers (i.e.,
      DNA). Hyperplasia and hypertrophy played a role in growth of the forestomachs,
      although cell numbers and sizes tended to change in opposite directions, limiting
      magnitudes of changes in organ mass. Protein synthetic capacity (i.e., RNA)
      varied as well, often in parallel with cell number. This result differed from
      that observed in intestines, which maintained constant cell sizes but underwent
      marked changes in cell number. For liver, amounts of absorbed nutrients seemed to
      be the main factor driving hypertrophy. The organs of the gastrointestinal tract
      responded to physical and chemical signals, as shown by the effects of dietary
      fiber on growth of the forestomachs and intestines. Forestomachs responded mainly
      to diet fiber content, whereas the intestines responded to diet type and nutrient
      supply. Feeding programs for beef animals often include changes in diet type and
      periods of feed limitation, and these in turn affect visceral organ growth and
      metabolism. Because visceral organs are a major contributor to whole-body energy
      expenditures, factors affecting these tissues must be understood. This study
      supports the concept that workload determines organ size, but dietary factors
      influencing workload clearly vary for each organ.

PMID- 9159270
TI  - Compensatory growth in runt pigs is not mediated by insulin-like growth factor I.
AB  - Runt pigs grow more slowly and never reach the same body weight as age-matched
      littermates. We hypothesized that IGF-I would be reduced in the runts and that
      postnatal nutrition would alter IGF-I concentration and tissue expression. Runt
      and control littermates were removed from 20 crossbred sows 20 to 28 h after
      birth. Tissues were collected from a baseline group (n = 4). The remaining pigs
      were fed porcine milk replacer at either 70 or 120 g/kg BW for 14 d (n = 8). Feed
      intake and body weight were measured daily, with plasma samples collected by
      jugular venipuncture throughout the experiment. Expression of IGF-I mRNA was
      measured in the liver and gastrocnemius with an RNase protection assay. At d 0,
      runts were significantly smaller than controls in all measurements, except brain
      weight. During the 14 d, the relative rate of growth was significantly faster and
      more efficient in runts than in controls; however, runts never attained the same
      absolute body weight as controls. Circulating IGF-I was significantly reduced at
      d 0 but was similar to that in controls by d 2 of feeding. The IGF-I mRNA
      expression in liver or gastrocnemius muscle was not different between control and
      runts at d 0 or 14 and was not affected by dietary intake. This study has shown
      that runt pigs grow in a compensatory manner for at least the first 2 wk of life.
      However, this growth response does not seem to be mediated by IGF-I.

PMID- 9159271
TI  - Inhibition of growth by pro-inflammatory cytokines: an integrated view.
AB  - In response to antigenic stimuli, a variety of cells, including activated
      macrophages, secrete cytokines that are responsible for altering the host's
      metabolism. Three of these cytokines (tumor necrosis factor alpha [TNF-alpha],
      interleukin-1 [IL-1], and interleukin-6 [IL-6]) have profound behavioral,
      neuroendocrine, and metabolic effects. There is evidence that cytokines and their
      cognate receptors are present in the neuroendocrine system and brain. Moreover,
      in laboratory animal species, IL-1, IL-6, and TNF-alpha have been found to
      modulate intermediary metabolism of carbohydrate, fat, and protein substrates,
      regulate hypothalamic-pituitary outflow, and act in the brain to reduce food
      intake. Finally, many of the systemic acute-phase responses to inflammatory
      stimuli such as lipopolysaccharide are inhibited by treatment with cytokine
      receptor antagonists. In short, many findings converge to suggest that a major
      component of the growth inhibition observed in immunologically challenged animals
      is mediated by pro-inflammatory cytokines. The goal of this article is to provide
      an integrated view of how cytokines act systemically on disparate tissues to
      alter growth.

PMID- 9159272
TI  - Anabolic implant effects on steer performance, carcass traits, subprimal yields,
      and longissimus muscle properties.
AB  - Crossbred steers (n = 140; 353 kg) were implanted as follows: (C) control, no
      implant; (S) Synovex-S (20 mg estradiol benzoate + 200 mg progesterone); (R)
      Revalor (20 mg estradiol + 140 mg trenbolone acetate [TBA]; international
      dosage); (ST) S + finaplix-S (140 mg TBA); (STT) S + finaplix-S with finaplix-S
      reimplanted on d 58. Steers were harvested after 119 to 126 d on feed. Left sides
      of 40 carcasses were fabricated into boneless subprimals for two s.c. fat levels:
      2.5 and .64 cm. Steers administered an estrogen (estradiol benzoate or estradiol)
      plus TBA gained more rapidly (P < .05) than C or S steers. Feed efficiency was
      improved (P < .05) with an estrogen plus TBA. No differences (P > .05) were noted
      among treatments for carcass s.c. fat thickness, percentage internal fat, or lean
      color. Carcasses from steers receiving TBA had larger (P < .05) longissimus areas
      and tended to have lower (P < .10) marbling scores and yield grades than C or S
      steers. Steers implanted with R had a lower (P < .05) percentage of U. S. Choice
      carcasses (51.8%) than C, S, and ST steers (82 to 86%). Shear force values for
      implanted steers tended to be higher (P < .10) than for controls. Implants
      increased (P < .05) subprimal and total side lean yields (.64 cm) compared to
      controls; the largest increases of 2.3 and 2.8%, respectively, occurred in steers
      receiving TBA plus an estrogen. Estrogen plus TBA exhibited favorable effects on
      gain, efficiency, and composition; however, the single estradiol plus TBA implant
      (R) decreased quality grade.

PMID- 9159273
TI  - Plasma amino acid uptake by the mammary gland of the lactating sow.
AB  - The objectives of this study were to measure arteriovenous concentration (A-V)
      differences and estimate uptake of amino acids across the mammary gland in
      lactating sows. Four sows were used in Trial 1 and nine sows in Trial 2. Cannulas
      were fitted in the right anterior mammary vein and the carotid artery around d 7
      of lactation. Arteriovenous samples were obtained on d 11, 14, 17, and 20.
      Litters were separated from the sows for 90 min, after which the first blood
      samples were drawn. Samples were taken at 20-min intervals for the next two
      consecutive hours. Milk production measurements and milk samples were obtained
      between d 11 and 19. Liters of plasma to liters of milk ratio (conversion
      coefficient) was estimated with the Fick method using A-V difference for lysine
      and milk lysine concentration. The conversion coefficient and the daily plasma
      flow were 541.41 +/- 35.72 L of plasma per liter of milk and 4,275 +/- 386 L of
      plasma, respectively. The A-V differences and the plasma flow were used to
      quantify daily amino acid uptake by the mammary gland. Uptake estimates
      (grams/day) were 36.51 +/- 4.05 (leucine), 31.24 +/- 3.64 (arginine), 23.39 +/-
      2.97 (lysine), 21.22 +/- 1.96 (valine), 18.36 +/- 1.92 (isoleucine), 15.9 +/- 1.9
      (threonine), 15.46 +/- 1.58 (phenylalanine), 7.61 +/- 1.12 (histidine), and 6.54
      +/- 2.01 (methionine). The uptakes of arginine, leucine, isoleucine, valine,
      phenylalanine, and threonine significantly exceeded output of these amino acids
      in the milk. These results indicate that the sow mammary gland retains specific
      amino acids above requirements for milk protein synthesis.

PMID- 9159274
TI  - A modification to the isotope-dilution technique for estimating milk intake of
      pigs using pig serum.
AB  - The aim of this study was to compare the measurement of deuterium oxide (D2O)
      directly in pig serum with that in sublimed whole blood. This was to assess
      whether excluding vacuum sublimation before analysis would cause any significant
      loss of accuracy in estimates of pig milk intake. Water and serum standards were
      made in deionized water and serum, respectively, and were assayed with samples
      under the same conditions on a fixed-filter, infrared spectrophotometer. The mean
      concentration of D2O in sublimed samples was 2,244 microg/mL of body water, and
      the mean concentration of D2O in serum samples was 2,184 microg/mL of body water.
      The mean ratio of D2O concentration in deionized water to the D2O concentration
      in serum was 1.0275, which was used as a correction factor to convert serum D2O
      concentration to D2O concentrations in body water. Using this method, the mean
      concentration of D2O in all serum samples was identical to that in sublimed
      samples (i.e., 2,244 microg/mL of body water). Mean milk intake of pigs based on
      sublimed samples was 1,006 g/d and that based on serum samples was 1,012 g/d.
      This confirms that milk intake determined from measurement of D2O directly in pig
      serum is sufficiently precise.

PMID- 9159276
TI  - Soaking increases the efficacy of supplemental microbial phytase in a low
      phosphorus corn-soybean meal diet for growing pigs.
AB  - Sixty-three crossbred barrows averaging 18.7 kg initial BW were used in a 6-wk
      study of the effects of soaking on the efficacy of supplemental microbial phytase
      (Natuphos, BASF) in a low-P corn-soybean meal diet. The basal corn-soybean meal
      diet contained .06% available P, .32% total P, and .55% Ca with no added
      inorganic P. The basal diet was supplemented with 0, 250, or 500 phytase units
      (PU)/kg of diet. The diet was fed dry or soaked (2 parts water:1 part diet and
      mixed for 2 h at 30 degrees C before feeding) in a 3 x 2 factorial arrangement. A
      positive control diet was supplemented with inorganic P and provided .23%
      available P, .48% total P, and .60% Ca. Pigs were individually penned and fed
      their respective diets to appetite in four equal meals daily. There were no
      soaking x phytase interactions (P > .1 to .6) for growth performance criteria.
      Daily gain and gain/feed ratio were increased (P < .01) by soaking and increased
      linearly (P < .01) by phytase. Daily feed intake was increased linearly (P < .01)
      by phytase. There were soaking x phytase quadratic interactions (P < .01) for
      apparent P absorption criteria because soaking the 250 PU/kg diet increased P
      absorption similar to that obtained with the 500 PU/kg diet fed dry. Apparent P
      absorption criteria were increased by soaking (P < .01) and were increased
      linearly (P < .001) and quadratically (P < .03) by phytase. Phytase reduced fecal
      P excretion 37 to 40% with dry feeding (P < .03) and 48 to 49% with soaking (P <
      .01).

PMID- 9159275
TI  - The effect of microbial phytase in a pearl millet-soybean meal diet on apparent
      digestibility and retention of nutrients, serum mineral concentration, and bone
      mineral density of nursery pigs.
AB  - Eighteen gilts (initial BW of 10.9 kg; age 4 wk) were used in a 35-d experiment
      to study the effects of adding microbial phytase to a pearl millet-soybean meal
      based diet on growth, apparent digestibility and retention of nutrients, and bone
      mineral status. The dietary treatments were arranged in a 2 x 3 factorial with
      two levels of P (.58%, low-P or .95%, adequate-P) and three levels of microbial
      phytase (0, 700, or 1,000 units/kg of diet). Phosphorus, Ca, and N balance were
      determined from d 32 to 35. Blood samples were collected on d 0 and 35 for serum
      mineral analysis. Global bone mineral content (GBMC) and global bone mineral
      density (GBMD) were determined on d 0 and 35 using dual-energy x-ray
      absorptiometry (DXA). A microbial phytase level x P level interaction was
      observed for final BW, ADG, gain:feed (P < .001), and serum P concentration (P <
      .003). Phytase supplementation of the low-P diets increased final BW, ADG, gain:
      feed, and serum inorganic P concentration but did not improve growth or serum
      inorganic P concentration in pigs fed the adequate-P diets. The addition of
      microbial phytase to the low-P and adequate-P diets reduced fecal P (P < .01),
      fecal N (P < .05), increased P absorption and retention (P < .01), and increased
      N absorption (P < .05). Pigs fed the adequate-P diets absorbed more P (P < .01)
      but excreted more P (P < .01) in the feces. Phytase tended to increase Ca (P <
      .07) and N (P < .10) retention, apparent threonine digestibility (P < .06), and
      serum Zn concentration (P < .09). Phytase increased GBMC and GBMD (P < .04).
      Phosphorus also increased GBMC and GBMD (P < .007 and P < .002, respectively).
      These results show that supplemental microbial phytase in pearl millet-soybean
      meal diets increased P availability, decreased the amount of P excreted in feces,
      and increased bone mineralization in nursery pigs.

PMID- 9159277
TI  - Efficacy of Natuphos in sorghum-based diets of finishing swine.
AB  - The efficacy of a recombinantly derived microbial phytase (Natuphos 5000, BASF
      Corp.) was evaluated in sorghum-soybean meal-based diets of finishing swine.
      During the 50- to 80- and 80- to 118-kg BW intervals, diets contained .40 and
      .39% plant P, respectively; control diets fed during the two weight intervals
      were supplemented with .08 and .04% inorganic P from dicalcium phosphate. The all
      plant-P diets were supplemented with 0, 300, or 500 phytase units (FTU) per
      kilogram of diet. Supplemental P (P = .09) and phytase (linear, P = .01)
      increased growth rate but did not affect feed efficiency. Dietary treatment did
      not affect quantitative carcass traits, CP, fat, or moisture content of the loin
      or taste panel scores of the cooked loin other than a quadratic decrease (P =
      .02) in connective tissue amount as phytase supplementation increased. Apparent
      ileal and total tract digestibilities of DM, GE, and N were not affected (P >
      .25) by phytase supplementation, whereas ileal and total tract digestibilities of
      Ca and P increased (P < .05 or P < .01) with increasing phytase supplementation.
      Ultimate load and ash content of the third and fourth metacarpals and metatarsals
      and serum P levels increased in response to inorganic P and phytase
      supplementation. Pig performance, carcass traits, and bone traits were
      essentially equal for the 300 and 500 FTU/kg treatments. These results show that
      phytase effectively liberates P in sorghum-based diets, and that 300 FTU/kg (or
      less) will optimize performance and carcass merit of finishing swine.

PMID- 9159278
TI  - Digestible phosphorus needs of terminal-cross growing-finishing pigs.
AB  - Growth and digestion experiments were conducted to estimate the digestible P
      needs of terminal-cross growing-finishing pigs fed sorghum-soybean meal-based
      diets from 25 to 118 kg. Dietary available P levels approximated the levels
      recommended by the NRC (1988) or were approximately 25% above or below those
      levels. Up to 80 kg, dietary treatment did not affect performance; from 80 to 118
      kg, the lowest P level (no inorganic P) reduced (P = .03) feed efficiency.
      Carcass leanness, subjective quality scores for the loin, chemical content of
      lean, and sensory evaluation of cooked lean were not adversely affected by
      decreasing P. As dietary P decreased, connective tissue amount in the lean
      decreased (P = .06). Ash content (P < .01) and peak load (P < .05) of metacarpals
      and metatarsals decreased as dietary P decreased, but structural soundness scores
      in the live pig were unaffected by treatment. Apparent digestibility of P
      decreased (P = .08 to P < .01) as dietary P decreased in the diets. Estimated P
      excretions per pig decreased with decreasing dietary P up to 80 kg; during the 80
      to-118-kg interval, P excretions were similar for pigs fed the two lowest P diets
      due to reduced feed efficiency of pigs fed the lowest P diet. Dietary digestible
      P contents maximizing performance and carcass merit were .21, .19, and .16% for
      pigs fed from 25 to 50, 50 to 80, and 80 to 118 kg, respectively. The results
      suggest that P excretions of terminal-cross pigs can be reduced by feeding less
      than current NRC recommendations for P without reducing performance, carcass
      merit, or structural soundness of live pigs.

PMID- 9159279
TI  - Supplemental chromium picolinate influences nitrogen balance, dry matter
      digestibility, and carcass traits in growing-finishing pigs.
AB  - Four trials were conducted to determine the influence of feeding 200 ppb Cr as
      chromium picolinate (CrPic) on DM digestibility, N balance, and carcass traits of
      growing-finishing pigs. A 15% CP corn-soybean meal diet was fed during the grower
      phase, and a 13% CP corn-soybean meal diet was fed during the finisher phase. In
      each of three trials, crossbred barrows (six littermate pairs) were used for two
      N balance periods (end of grower, 61.3 kg; end of finisher, 98.9 kg). After the
      second balance period, all the barrows were killed and carcass data were
      collected. Initial and final BW were 23.5 and 104.9 kg, respectively. Growth rate
      was similar for control and CrPic-fed pigs in all trials. The rate of N
      absorption was increased by feeding CrPic (P < .05), but N retention was
      increased only numerically (P = .14). Dry matter digestibility was also increased
      by feeding CrPic (P < .02). Dressing percentage and backfat thickness at the 10th
      and last rib did not differ between treatment groups. Longissimus muscle area was
      larger (P < .05) for pigs fed CrPic. In Trial 4, crossbred barrows (six
      littermate pairs; initial BW, 82.0 kg) were used in a switch-back design with an
      extra period. Digestibility of DM (P < .02) and absorption of N (P < .06) were
      improved with only a numerical increase (P = .22) in N retention. No carryover
      effect was observed. These findings show that pigs fed 200 ppb Cr from CrPic can
      have larger longissimus muscle areas and that Cr supplementation improved N
      absorption and DM digestibility.

PMID- 9159280
TI  - Pancreatic exocrine secretion during the first days after weaning in pigs.
AB  - Feed replacement at weaning plays an important role in the induction of
      pancreatic maturation. To understand the changes in the exocrine pancreas at
      weaning and the relation to postweaning problems, we studied the function of the
      exocrine pancreas and changes of intestinal hemolytic Escherichia coli in four
      pigs. The pigs were chronically fitted with pancreatic duct catheters and T
      shaped cannula inserted into the duodenum for reintroduction of pancreatic juice.
      One day before weaning (at 30 d of age), pancreatic juice was collected for 1 h
      before and 1 h after a morning and an evening suckling. The pigs were not creep
      fed, but from weaning the pigs received a standard weaning diet ad libitum. On d
      1, 2, 3, and 5 after weaning, pancreatic juice was collected continuously for the
      24-h period. The total pancreatic secretion was measured at hourly intervals, 1.5
      mL samples were taken for analysis, and the remaining juice was returned to the
      animal. On these days, samples from the duodenum, ileum, and rectum were also
      taken for analyses of hemolytic E. coli. From the day before to 5 d after
      weaning, a gradual increase in pancreatic secretion was observed concerning
      volume (P < .001) and protein (P < .01) and trypsin (P < .02) levels. An increase
      (P < .01) in hemolytic E. coli in the duodenal contents was also documented
      during this period. We assume that the gradual increase in the measured variables
      of pancreatic secretion is related to the increasing consumption of solid feed.
      However, the appearance of E. coli and disappearance of milk components from the
      gastrointestinal tract could be other factors stimulating the exocrine pancreas.

PMID- 9159281
TI  - Culture of bovine embryos in buffalo rat liver cell-conditioned media or with
      leukemia inhibitory factor.
AB  - Experiments were designed to study development of bovine embryos in TCM-199
      medium conditioned by preculture with buffalo rat liver (BRL) cells. Conditioned
      media were harvested after BRL cells were cultured until confluency (CON), or for
      an additional 2 d with the same cells but new medium (CON-N) or the same medium
      (CON-S). Glucose in TCM-199 was depleted by BRL cells to different concentrations
      depending on coculture procedures: CON = 3.94 mM, CON-N = 1.67 mM, and CON-S =
      1.11 mM glucose. In Exp. 1, development of bovine zygotes in CON-S resulted in
      fewer blastocysts than development in CON (10 vs 28%, P < .05); CON-N was not
      different from CON (26% blastocysts). Experiment 2 examined effects of moving
      embryos to a fresh drop of different or identical conditioned medium after
      culture for 3 d. Initial culture in CON-N and final culture in CON resulted in a
      greater (P < .01) number of blastocysts compared with the control of CON followed
      by CON (32 vs 19% blastocysts). This was not entirely due to changing from low to
      high glucose because adding glucose to CON-N after 3 d yielded only 18%
      blastocysts. To test the hypothesis that beneficial effects of BRL cell
      conditioned media may be due to secretion of leukemia inhibiting factor (LIF),
      LIF was added to B2, a more appropriate medium than Medium-199 for culturing
      bovine embryos without conditioning or coculture with BRL cells. In the absence
      of serum, the percentage of blastocysts per cleaved embryo (17 to 28%) was not
      improved with LIF; however, the mean number of cells per blastocyst was higher (P
      < .05) in treatments with LIF (65 to 74 cells) than without LIF (47 cells). In B2
      medium + 10% fetal calf serum, LIF was of no benefit; development to blastocysts
      was good with or without LIF (43% of cleaved).

PMID- 9159282
TI  - Effect of number of pig embryos in the uterus on their survival and development
      and on maternal metabolism.
AB  - The effects of pig embryo number on fetal survival and growth and maternal
      metabolism were evaluated with 114 Large White gilts. Gilts were assigned at 38
      kg to three treatments: control (CTR), ligature of the left oviduct (LIG), or
      right hemi-hysteroovariectomy (HHO). Insemination occurred at 311 +/- 18 d of
      age. A laparotomy was performed at d 35 of gestation, and gilts were slaughtered
      at d 112. Ovulation rate per uterine horn was 4.30, 8.70, and 17.12 in the LIG,
      CTR, and HHO groups, respectively. The hierarchy was the same for litter size at
      d 35 of gestation, but the relative differences were reduced (3.24, 5.98, and
      8.40 fetuses/uterine horn, respectively). Litter size per uterine horn was
      similar in the CTR and HHO groups at d 112 of pregnancy (2.93, 4.69, and 4.76
      fetuses in the LIG, CTR, and HHO groups, respectively). Early (before d 35 of
      gestation), late, and total fetal mortality increased with embryo potential per
      uterine horn. There was a compensation between early and late fetal mortality in
      the CTR and HHO groups. Fetal weight at d 112 was related to litter size in early
      pregnancy (1.50, 1.38, and 1.27 kg in the LIG, CTR, and HHO groups,
      respectively). Uterine capacity limits litter size and fetal development, even in
      sows with a conventional potential of embryos. Availability of energetic and
      gluconeogenic substrates was higher at 110 than at 60 d of gestation in the three
      groups. Blood substrate levels suggested that lipid mobilization and glucose
      uptake were higher in the gilts with a larger litter weight.

PMID- 9159283
TI  - Fertility in estrus-cycling and noncycling virgin heifers and suckled beef cows
      after induced ovulation.
AB  - A procedure was developed to either induce or synchronize ovulation in heifers
      and suckled cows. Beef females were assigned to two breeding programs: 1) two
      injections of prostaglandin F2alpha (PGF2alpha) given 14 d apart to synchronize
      estrus (PGF2alpha control; n = 179), with inseminations 12 to 16 h after detected
      estrus or at 80 h in the absence of estrus, or 2) two injections of PGF2alpha (d 
      14 and 0) plus 100 microg of GnRH on d -7 when 6 mg of norgestomet was implanted
      (PGF2alpha/NORG/GnRH treatment; n = 173). Implants were removed 24 h after the
      second PGF2alpha injection (d +1) and females were inseminated 12 to 16 h after
      detected estrus until 54 h after PGF2alpha. The remaining cattle were given a
      second 100-microg GnRH injection 54 h after PGF2alpha and inseminated 18 to 20 h
      later. Percentages of noncycling females with subsequently elevated progesterone
      (P4) on d 0 or +1 were not different between treatment groups (20.4 vs 25%), but
      conception rate was greater (P < .05) in noncycling treated females than in
      noncycling controls (55 vs 12.8%). Conception rates in cycling (59.2%) and
      noncycling (62.2%) treated females were similar to those in cycling controls
      (56.2%) but greater (P = .06) than those in noncycling controls (26.5%).
      Conception rates in treated females inseminated 12 to 16 h after detected estrus
      (63.1%) or at one fixed time (58.3%) were similar to those in controls
      inseminated 12 to 16 h after detected estrus (68.7%). This treatment procedure
      produced fertility after one timed insemination that was equal to controls
      inseminated after detected estrus and induced equally fertile ovulations in
      noncycling heifers and cows.

PMID- 9159284
TI  - Acute effects of short-term feed deprivation and refeeding on circulating
      concentrations of metabolites, insulin-like growth factor I, insulin-like growth
      factor binding proteins, somatotropin, and thyroid hormones in adult geldings.
AB  - Two studies were performed with Standardbred geldings 7 to 21 yr of age to
      determine the sequence of changes in blood plasma concentrations of some hormones
      and metabolites during feed deprivation for 48 h and for 12 h after refeeding.
      Plasma hormone and metabolite concentrations were determined with methods
      validated for horse plasma. Insulin-like growth factor binding proteins (IGFBP)
      were determined with radioligand analysis following SDS-PAGE electrophoresis. In
      both experiments, plasma concentrations of triiodothyronine and thyroxine
      decreased (P < .01) during feed deprivation and increased (P < .01) during
      refeeding. Plasma glucose and IGF-I either decreased or were not altered during
      feed deprivation. In contrast, plasma concentrations of NEFA and urea nitrogen
      increased (P < .01) during feed deprivation and decreased (P < .01) during the
      refeeding period. Plasma somatotropin (ST) increased (P < .01) approximately 80%
      at 24 to 36 h of feed deprivation, declined (P < .01) to control values at 48 h
      of feed deprivation, increased (P < .01) nearly three fold at 3 h after
      refeeding, and returned to control values by 6 h after refeeding. We identified
      five IGFBP, and their plasma concentrations were not significantly altered during
      feed deprivation or following refeeding. We conclude that metabolite availability
      during feed deprivation and following refeeding alters the secretion of thyroid
      hormones, ST, and possibly IGF-I, thereby maintaining homeostasis in horses.

PMID- 9159285
TI  - Methscopolamine bromide blocks hypothalamic-stimulated release of growth hormone
      in ewes.
AB  - Twenty-five nonlactating ewes were used to test the hypothesis that
      methscopolamine bromide (MB) blocks secretion of growth hormone (GH) by affecting
      hypothalamic rather than pituitary mechanisms. Ewes were randomly assigned to
      receive a s.c. injection of 96 mg of MB or 2 mL of saline at min = 0. Saline
      treated ewes were assigned to receive a subsequent (at +60 min) i.v. injection of
      10 microg of growth hormone-releasing hormone (GHRH) to test pituitary
      responsiveness or .3 mg of clonidine to test hypothalamic responsiveness.
      Methscopolamine bromide-treated ewes were assigned to receive a subsequent (at
      +60 min) i.v. injection of 10 microg of GHRH, .3 mg of clonidine, or 2 mL of
      saline. Jugular blood samples were collected at 10-min intervals from -120 min to
      +240 min, and serum concentrations of GH were quantified with a RIA. No
      difference was detected in serum concentrations of GH with respect to MB vs
      saline treatment (P = .20). Concentrations of GH increased in saline-pretreated
      ewes following injections of clonidine or GHRH (P < .01). Treatment of ewes with
      MB, however, limited the ability of clonidine-induced mechanisms to increase
      concentrations of GH, but did not affect pituitary responsiveness to GHRH (P <
      .01). These data support the hypothesis that MB inhibits hypothalamic and not
      pituitary mediated mechanisms that regulate the secretion of GH.

PMID- 9159286
TI  - Prolonged increased concentrations of 17beta-estradiol associated with
      development of persistent ovarian follicles do not influence conception rates in
      beef cattle.
AB  - Objectives were to evaluate conception rates and time to estrus following
      cessation of treatments designed to either cause prolonged elevated
      concentrations of 17beta-estradiol associated with development of persistent
      ovarian follicles or to inhibit elevated concentrations of 17beta-estradiol and
      development of persistent ovarian follicles. Beef heifers (n = 80) and 2-yr-old
      nonlactating cows (n = 39) were stratified by age, blocked by estrual status
      (previously exhibited estrus or anestrus) and assigned to receive either 1) four
      norgestomet implants (4 Norg; n = 59) for 9 d (d 0 = treatment initiation) or 2)
      one norgestomet implant from d 0 to 7 and three additional norgestomet implants
      from d 7 to 9 (1 + 3 Norg; n = 60). All animals received PGF2alpha on d 0 to lyse
      corpora lutea. All implants were removed on d 9 followed by estrus detection
      every 6 h for 7 d following implant removal. Females exhibiting estrus were
      artificially inseminated 6 to 12 h after detection of estrus. A treatment x day
      interaction (P < .01) for concentrations of 17beta-estradiol from d 0 to 9 of the
      experiment with elevated 17beta-estradiol occurring in females treated with 1 + 3
      Norg implants. The interval from treatment withdrawal to estrus was longer (P <
      .01) in females treated with 1 + 3 Norg (105 h) than in those treated with 4 Norg
      (61 h). Synchrony of estrus among anestrous females was greater (P < .10) in
      females treated with 4 Norg (97%) than in females treated with 1 + 3 Norg (67%)
      but was similar in estrual females. Conception rates (number conceiving to
      AI/number bred by AI) did not differ (4 Norg = 67%; 1 + 3 Norg = 72%; P > .10).
      Pregnancy rates (number conceiving to AI/number in treatment group) also did not
      differ between treatment groups of either estrual or anestrous females.
      Conception rates are not compromised in females that develop persistent ovarian
      follicles and have prolonged elevated concentrations of 17beta-estradiol when
      persistent ovarian follicles are not allowed to ovulate.

PMID- 9159287
TI  - Changes in forage quality, ingestive mastication, and digesta kinetics resulting
      from switchgrass maturity.
AB  - Five maturities of switchgrass hay harvested at 14-d intervals (vegetative
      through 20% heading) were fed to Hereford steers (297 kg) in a 5 x 5 Latin
      square. Relationships with switchgrass maturity were negative and quadratic (P <
      .05) for DMI and cubic (P < .05) for digestible DMI. Declines in apparent
      digestibilities of DM, ADF, and cellulose were cubic (P < .05), whereas these
      were quadratic (P < .05) for NDF, hemicellulose, and CP. Whole masticates from
      the least, mid, and most mature hays showed linear (P < .05) declines in DM
      concentration and IVDMD with increasing maturity, whereas NDF concentrations
      increased linearly (P < .05). Mean retention time of gastrointestinal DM
      increased linearly (P < .01) from 64 to 94 h from the least to the most mature
      hay, and the associated rate of passage declined linearly (P < .01) from 3.3 to
      2.1%/h. Sieving of masticate DM showed a reduced proportion of large particles (>
      or = 2.8 mm) and an increased proportion of small particles (< or = .5 mm) with
      advancing forage maturity. More than 94% of the sieved fecal DM passed a 1.0-mm
      sieve, but particle sizes showed the same relationship with forage maturity as
      noted for masticate DM. This occurred despite the comminution from the rumination
      and digestive processes.

PMID- 9159288
TI  - Omasal sampling technique for assessing fermentative digestion in the forestomach
      of dairy cows.
AB  - A procedure allowing digesta sampling from the omasum via a ruminal cannula
      without repeated entry into the omasum was developed. The sampling system
      consisted of a device inserted into the omasum via the ruminal cannula, a tube
      connecting the device to the ruminal cannula, and a single compressor/vacuum
      pump. Eight cows given ad libitum access to a total mixed diet were used in a
      crossover design to evaluate the effects of the sampling system on digestive
      activity, animal performance, and animal behavior. Results indicated that the
      omasal sampling system has minimal effect on normal digestive and productive
      functions of high-producing dairy cows. Dry matter intake was reduced (24.0 vs
      21.8 kg/d; P < .02) and seemed related more to the sampling procedures than to
      the device in the omasum. Observations of animal behavior indicated that cows
      with the sampling device were similar to control cows, although rumination and
      total chewing times were reduced slightly. The composition of digesta samples was
      biased toward an over-abundance of the liquid phase, but using a double-marker
      system to calculate digesta flow resulted in fairly small coefficients of
      variation for measurements of ruminal digestion variables. This technique may
      prove useful for partitioning digestion between the fermentative portion of the
      forestomach and the lower gastrointestinal tract. The omasal sampling procedure
      requires less surgical intervention than the traditional methods using abomasal
      or duodenal cannulas as sampling sites to study forestomach digestion and avoids
      potentially confounding endogenous secretions of the abomasum.

PMID- 9159289
TI  - Effect of increasing proportion of supplemental nitrogen from urea on intake and
      utilization of low-quality, tallgrass-prairie forage by beef steers.
AB  - Five Angus x Hereford steers with ruminal and duodenal fistulas were used in a 5
      x 5 Latin square to determine effects of increasing the proportion of urea in
      supplemental degradable intake protein (DIP) on intake, fermentation, and
      digestion. Steers had ad libitum access to low-quality, tallgrass-prairie forage
      (2.4% CP, 76% NDF). Supplemental DIP (380 g/d) was from sodium caseinate and(or)
      urea and was balanced with cornstarch to provide a final supplement
      (approximately 939 g DM/d) that contained 40% CP. The percentages of supplemental
      DIP from urea were 0, 25, 50, 75, and 100%. Intake of forage OM was not affected
      (P > or = .30) by urea level. Ruminal and total tract digestibilities of OM and
      NDF generally responded in a quadratic manner (P < or = .09) to increasing urea,
      with the lowest values observed at the highest urea level. As a result,
      digestible OM intake (DOMI) declined (linear, P = .03) with increasing
      proportions of urea and tended (quadratic, P = .14) to exhibit the largest
      proportional decline at the highest urea level. The effects of increasing urea on
      duodenal N flow, microbial efficiency, ruminal contents, and fluid dilution rate
      were minimal. Ruminal ammonia N and molar percent acetate increased linearly (P <
      or = .02), whereas most other VFA (except propionate) decreased (P < or = .05)
      with increasing urea. In conclusion, although forage OM intake was not altered,
      OM digestion, NDF digestion, and DOMI were lowest when all supplemental DIP was
      supplied as urea. Changes in fermentation characteristics reflected the change in
      source of available nitrogen.

PMID- 9159291
TI  - Nutritional value of pearl millet for lactating and growing goats.
AB  - Studies were conducted to assess nutritional value of pearl millet grain
      (Pennisetum glaucum [L] R. Br.) for lactating and growing goats. Three complete
      diets containing either 40% corn, 40% pearl millet, or 40% corn and pearl millet
      mixed 1:1 (wt/wt) were balanced to contain 16% crude protein and 2.24 Mcal DE/kg
      on an air-dry basis. Forty-five does were blocked by kidding date and randomly
      assigned to diets for a 7-wk investigation. Feed intake and milk production were
      unaffected (P > .25) by treatment, and they averaged 2.86 and 2.47 kg daily,
      respectively. Thirty-three growing goats were blocked by sex and fed the same
      diets for 15 wk. Daily growth rate and feed to gain ratio were depressed (P <
      .05) by 25.4 and 19.0%, respectively, when corn was completely replaced with
      pearl millet. Digestion coefficients for DM, GE, CP, and NDF were reduced by over
      10 percentage units with partial or complete replacement of corn by pearl millet.
      Ruminal acetate and ratio of acetate to propionate increased (P < .05) but
      butyrate, propionate, and ammonia were depressed (P < .05) with the pearl millet
      diets. Growing goats consumed 43 meals daily. They consumed 26.9, 32.6, 27.4, and
      13.1% of their ration during the morning (0600 to 1200), afternoon (1200 to
      1800), evening (1800 to 2400), and night (2400 to 0600), respectively. Pearl
      millet is a useful energy feed for mature, but not for growing, goats.

PMID- 9159290
TI  - The effects of copper deficiency with or without high dietary iron or molybdenum
      on immune function of cattle.
AB  - Two experiments were conducted to determine the effects of Cu deficiency with or
      without high dietary Mo or Fe on the specific immunity of calves. In Exp. 1,
      calves from 38 bred heifers, fed corn silage-based experimental diets from the
      last third of gestation until the calves were weaned, were used. Dietary
      treatments were control (no supplemental Fe, Mo, or Cu), 600 mg of supplemental
      Fe/kg of DM, 5 mg of supplemental Mo/kg of DM, and 10 mg of supplemental Cu/kg of
      DM. In Exp. 2, 18 Holstein bull calves were fed commercial milk replacer low in
      Cu for 49 d and then fed semipurified diets containing approximately 1.1 mg of
      Cu/kg of DM or diets supplemented with 5 mg of Mo or 10 mg of Cu per kilogram of
      DM for 126 d. Feeding diets not supplemented with Cu resulted in severe Cu
      deficiency in both experiments. During Exp. 1, control calves had higher (P <
      .10) secondary antibody response to pig erythrocytes than Cu-, Mo-, and Fe
      supplemented calves. During Exp. 2, in vitro Cu supplementation decreased (P <
      .01) lymphocyte blastogenic response. In vivo cell-mediated response to
      phytohemagglutinin was decreased (P < .10) by Cu supplementation during Exp. 1
      but was increased (P < .10) by Cu and Mo supplementation during Exp. 2. Copper
      deficiency and Cu deficiency coupled with high dietary Mo or Fe produced
      inconsistent immune function responses, indicating that Cu deficiency may not
      affect specific immune function of calves.

PMID- 9159292
TI  - Urea in dry-rolled corn diets: finishing steer performance, nutrient digestion,
      and microbial protein production.
AB  - In Exp. 1, 88 yearling steers (332 kg) were fed dry-rolled corn finishing diets
      to evaluate effects of dietary urea level on performance and carcass
      characteristics. Diets contained 0, .5, 1.0, or 1.5% urea (DM basis), which
      supplied all supplemental N, and 10% chopped prairie hay. Gains (P = .10) and
      gain efficiency (G/F; P < .05) were increased by .5% urea, with little
      improvement by additional urea. Regression analysis estimated optimal dietary
      urea at .9% of DM for ADG and G/F. Fat thickness (P < .05) and yield grade (P <
      .10) increased linearly with dietary urea level. In Exp. 2, four ruminally and
      duodenally cannulated steers (557 kg) were fed the diets used in Exp. 1 to
      evaluate effects of dietary urea on site and extent of digestion. True ruminal OM
      and starch digestion were increased 25 and 37%, respectively, by .5% urea, but
      higher urea levels did not differ from .5%. Flows of total N and microbial N to
      the duodenum were not affected by urea level. In Exp. 3, 100 yearling steers (347
      kg) were fed dry-rolled corn finishing diets that contained 10% alfalfa hay as
      the dietary roughage to evaluate effects of dietary urea level on performance and
      carcass characteristics. Urea levels were 0, .35, .70, 1.05, or 1.40% urea (DM
      basis), with no other supplemental N provided. Dry matter intake (P = .10), ADG
      (P < .05), and G/F (P < .05) increased with intermediate concentrations of urea
      but decreased with the highest concentration. Regression analysis indicated that
      the optimal dietary urea level was .5% of DM for ADG and G/F. Urea increased
      dietary energy utilization but not metabolizable protein supply.

PMID- 9159293
TI  - Rapid communication: detection and mapping of polymorphisms in the bovine
      Lactoperoxidase (LPO) gene and in the Glycosylation-dependent cell adhesion
      molecule 1 (GlyCAM1) gene using fluorescent single-strand conformation
      polymorphism analysis.

PMID- 9159294
TI  - Rapid communication: nucleotide sequence of rainbow trout alpha-globin I and IV
      cDNA.

PMID- 9159295
TI  - Rapid communication: mapping of leptin to bovine chromosome 4 by linkage analysis
      of a PCR-based polymorphism.

PMID- 9159296
TI  - Influence of metabolic acidosis on nutrition.

PMID- 9159297
TI  - A cost-effectiveness analysis of anemia screening before erythropoietin in
      patients with end-stage renal disease.
AB  - The treatment efficacy of erythropoietin (EPO) in end-stage renal disease (ESRD)
      can be limited by deficiencies of iron, folate, or vitamin B12, by
      hyperparathyroidism, or by aluminum intoxication. Since EPO costs are
      significant, this study attempted to determine the cost-effectiveness of
      performing a panel of screening tests for anemia before starting EPO. Anemia
      screening was performed prospectively in 48 new-onset ESRD patients at the Ralph
      H. Johnson Veterans Affairs Medical Center before EPO treatment was started.
      Serum iron, transferrin, folate, vitamin B12, parathyroid hormone, and aluminum
      levels were determined, and transferrin saturation (Tfsat) was calculated at the
      first dialysis session. At presentation for dialysis, the mean hematocrit was
      0.264 +/- 0.036 and the mean blood urea nitrogen was 32 +/- 2 mmol/L. Eighteen
      patients (37.5%) had a serum iron level lower than 7 micromol/L, suggesting iron
      deficiency. Twenty-five patients (52%) had Tfsat less than 0.20, consistent with
      overt iron deficiency. No patient was found to be vitamin B12 deficient, to be
      aluminum intoxicated, or to have significant hyperparathyroidism. One patient had
      folate deficiency. A cost-effectiveness analysis was performed assuming that (1)
      EPO would be given at an average starting dose of 6,000 U/wk at a cost of
      $14/2,000 U of EPO; (2) that without screening 1 month would elapse before a poor
      response was identified; and (3) that the failure to treat aluminum intoxication
      and hyperparathyroidism or to replete iron, vitamin B12, or folate deficiency
      would significantly impair the response to EPO. The Tfsat screen had a cost
      effectiveness ratio of 0.2019, saving approximately $5.00 in EPO use for each
      dollar of test administration. All other screens had cost-effectiveness ratios
      greater than 1.0, indicating that their testing costs exceeded dollar savings in
      EPO use. In conclusion, iron deficiency is common in anemic patients starting
      dialysis, but other causes of anemia are not. It is imperative that current
      clinical practices be influenced by cost-effectiveness considerations. Given the
      cost of laboratory screens, and the relative ineffectiveness of the other screens
      examined here to identify factors known to impair the response to EPO, anemia
      screening before initiating EPO therapy should be limited to tests to identify
      iron deficiency.

PMID- 9159298
TI  - Determinants of albumin concentration in hemodialysis patients.
AB  - Hypoalbuminemia predicts mortality in hemodialysis patients with end-stage renal
      disease and is assumed to result from malnutrition. To investigate a possible
      alternative cause, we evaluated the relationships between serum albumin (Salb)
      and serum levels of two positive acute-phase proteins: C-reactive protein (CRP)
      and serum amyloid A (SAA). We also examined the relationship between Salb and
      dialysis dose delivered (Kt/V) and normalized protein catabolic rate (PCRn)
      measured during 3 consecutive months in a group of 115 patients. Serum albumin
      was measured monthly for 5 months. SAA levels were not increased in the majority
      of patients, despite its low molecular weight (8 kd), and predialysis
      concentrations were independent of residual renal function, compatible with a
      nonrenal site of metabolism. Both CRP and SAA levels correlated negatively with
      Salb both by linear regression and by multiple regression analysis (P < 0.001).
      CRP correlated with fibrinogen (P < 0.005). Salb also correlated positively with
      PCRn (P = 0.001), but not with Kt/V. The Kt/V did not correlate with PCRn. While
      CRP and SAA correlated with one another, neither variable correlated with PCRn.
      When either SAA or CRP was high, Salb was low regardless of PCRn. Thus, there are
      two separate independent factors predicting Salb--markers of inflammation and
      protein intake--but high concentrations of acute-phase proteins have a greater
      impact on Salb than does low PCRn. Activity of the acute-phase response is an
      important predictor of low Salb in hemodialysis patients independently of
      nutritional factors.

PMID- 9159299
TI  - Sodium ramping in hemodialysis: a study of beneficial and adverse effects.
AB  - Sodium ramping has been introduced as a technique to decrease side effects
      occurring during hemodialysis. We studied sodium ramping in 414 dialysis sessions
      in 23 patients by randomizing 2-week blocks of dialysis to either steady
      dialysate sodium of 140 mEq/L, linear sodium ramping during dialysis from 155
      mEq/L to 140 mEq/ L, or stepwise ramping (sodium of 155 mEq/L for 3 hours and 140
      mEq/L for 1 hour). We studied the number and severity of hypotensive and
      hypertensive episodes. A hypotensive episode was defined as an abrupt decline of
      systolic blood pressure of more than 50 mm Hg, a decrease in blood pressure
      accompanied by symptoms requiring intervention, or systolic blood pressure of
      less than 90 mm Hg even without symptoms. A hypertensive episode was defined as a
      sudden increase in systolic blood pressure of over 30 mm Hg. We also recorded
      other side effects (headache, cramps, nausea, vomiting, dizziness, thirst,
      fatigue, weight gain, and blood pressure) during, immediately after, and between
      dialysis sessions. There was no major difference between the two ramping
      protocols, but compared with standard dialysis, both decreased total number of
      side effects from 4.0 to 3.0 (P = 0.057); the number of hypotensive episodes
      decreased from 1.3 to 0.7 (P = 0.036). The lowest blood pressure was 114/66 mm Hg
      during control and 123/69 mm Hg during ramping (P < 0.0001). The frequency of
      cramps during dialysis decreased from 0.9 to 0.5 (P = 0.006). There was no
      difference in headache, nausea, or vomiting. The number of hypertensive episodes
      increased from 0.045 to 0.086 during ramping (P = 0.125). Of 23 patients, only
      five (22%) had a marked decrease in symptoms; two of the three most symptomatic
      patients showed no significant improvement. Between dialysis sessions, patients
      complained of more fatigue and thirst (P < 0.0001 and P = 0.0028, respectively),
      and interdialytic weight gain following ramping was 5.1% of body weight compared
      with 4.4% without ramping (P < 0.0001). Blood pressure also increased following
      ramping, from 143/79 mm Hg to 152/81 mm Hg (P = 0.001). Ramping can decrease the
      overall number of side effects, but increases interdialytic symptoms, weight
      gain, and hypertension. In most instances, it simply changes the time the side
      effects occur. Only 22% of patients have significant benefit. These patients can
      be identified only through trial and error, as no model of these patients can be
      created.

PMID- 9159300
TI  - Ambulatory blood pressure monitoring in dialysis patients and estimation of mean
      interdialytic blood pressure.
AB  - To define blood pressure (BP) patterns and control in dialysis patients, 48-hour
      ambulatory BP monitoring was performed in 36 hemodialysis and 18 peritoneal
      dialysis patients. Monitoring began during a dialysis session for hemodialysis
      patients. Data revealed significantly lower diastolic BP (DBP) and lower
      diastolic load (percentage of diastolic values > 90 mm Hg) in hemodialysis
      patients compared with peritoneal dialysis patients (80.6 mm Hg v 88.8 mm Hg,
      respectively, [P < 0.03] and 26% v 45%, respectively [P < 0.03]) for the 48-hour
      period. When the 2 days were analyzed separately, the difference in diastolic
      pressures and loads was significant only for the first (dialysis) day. Similarly,
      trends toward lower systolic BP (SBP) and systolic load in hemodialysis patients
      existed throughout monitoring and were greater in magnitude during the first day.
      BP data were fit to a random-coefficient growth curve model to detect
      periodicity. This sensitive model did not detect diurnal variation of BP in
      either group. The incidence of hypotension did not differ between the two groups
      (2.0% v 1.0% of total observations, hemodialysis v peritoneal dialysis). In the
      hemodialysis group, the proportion of hypotensive observations was significantly
      greater during the 4 hours postdialysis compared with other periods (5.6% v 1.6%;
      P < 0.02), a finding that likely reflects the practice of holding
      antihypertensives until after hemodialysis. However, patient diaries did not
      reflect hypotensive symptoms during this time. In the hemodialysis group, mean BP
      and predialysis BP did not correlate with interdialytic sodium load or weight
      gain. Predialysis and postdialysis BP (recorded by dialysis nurses) correlated
      significantly with mean BP. Predialysis SBP overestimated mean SBP by an average
      of 10 mm Hg, while postdialysis SBP underestimated mean SBP by an average of 7 mm
      Hg. To create formulas to estimate mean SBP and DBP in hemodialysis patients,
      multiple linear regression was used to model these variables against age, sex,
      race, and average prehemodialysis/posthemodialysis BP. The model achieved a high
      degree of fit (r2 = 0.72 for SBP; r2 = 0.65 for DBP), demonstrating that
      prehemodialysis and posthemodialysis BP can be used to predict mean BP in
      hemodialysis patients. In summary, our data show the absence of a diurnal
      variation of BP in dialysis patients and lower BP in hemodialysis patients
      compared with peritoneal dialysis patients. Among hemodialysis patients, more
      hypotension occurred after dialysis compared with other periods, and predialysis
      and postdialysis BP can be used to model mean BP levels.

PMID- 9159301
TI  - Gynecologic and reproductive issues in women on dialysis.
AB  - Most women on dialysis are amenorrheic and do not ovulate, but little information
      about menstrual patterns in women on dialysis exists, especially since the
      introduction and use of recombinant human erythropoietin, a therapy that may
      improve sexual interest and function. In this study, women who were < or = 55
      years of age at the start of dialysis (n = 76) completed questionnaires and form
      the study group. Women older than 55 years at the start of dialysis did not
      complete the entire questionnaire (n = 115), but their medication records were
      reviewed for estrogen replacement therapy. The questionnaire asked about
      pregnancies, menstrual periods (regularity, frequency, duration, character of
      flow, menopause), and menopause before beginning dialysis and currently. Women
      also responded to questions about sexual activity, use of birth control,
      contraception counseling by physicians, yearly Papanicolaou smears, and
      mammograms. Demographic data (age, race, age at the time dialysis started, mode
      of dialysis, use of recombinant human erythropoietin, and history of renal
      transplant) were also obtained through the questionnaires. Fifty-nine percent of
      the 76 women who completed the study were white and had been on dialysis a median
      of 3 years (range, 0.1 to 18 years). The median age was 43 years, 68% were on
      hemodialysis, 90% were receiving recombinant human erythropoietin, and 70% had
      been pregnant (a total of 179 pregnancies; four pregnancies in four women
      occurred after the start of dialysis). Significantly more women were menstruating
      before dialysis started than currently (63% v 42%; P < 0.025), but the difference
      could be explained by patient age: currently menstruating women were younger (37
      +/- 9 v 46 +/- 11 years; P = 0.0002). More women reported menstrual regularity
      before beginning dialysis (75% v 42% currently; P < 0.005), but there were no
      differences in number of days between or number of days of menstruation before
      beginning dialysis and currently. Menstrual flow was reported as heavier
      currently by more women (64% heavy flow with clots v 38% before dialysis started;
      P < 0.05). The median age at menopause was 47 years; 28% of the women were
      postmenopausal. Fifty percent of the women were sexually active, but only 36%
      used birth control. Discussions between the women and their nephrologist about
      possible pregnancy and contraception were reported by only 13% of women. Sixty
      three percent of the women reported having yearly Papanicolaou smears and 73% had
      had a mammogram. Only 5% of the 113 women who were older than 55 years when they
      began dialysis were receiving estrogen replacement therapy. Amenorrhea was
      reported in this study by a smaller proportion of women than in studies conducted
      before the introduction of recombinant human erythropoietin. The possibility that
      erythropoietin may restore normal hormonal cyclic function in women with end
      stage renal disease requires further study. Nephrologists as well as primary care
      physicians and gynecologists need to focus more on the gynecologic concerns of
      women on dialysis, including the potential for pregnancy. The effects of estrogen
      replacement on atherosclerosis and osteoporosis, and consideration of such
      therapy in women on dialysis warrants attention.

PMID- 9159302
TI  - Changes in patients' eating behavior: in the uremic state, on continuous
      ambulatory peritoneal dialysis treatment, and after transplantation.
AB  - Nineteen predialysis patients (group A) were studied before and after 3 to 6
      months on continuous ambulatory peritoneal dialysis (CAPD) treatment. Six
      patients (group B) were studied during CAPD treatment and 3 to 6 months after
      transplantation. Nine uremic patients (group C) were studied before and 3 to 6
      months after transplantation. The patients were invited to a single test meal by
      means of the universal eating monitor VIKTOR. An excess portion of hash was
      served on a plate placed on a hidden scale that was connected to a computer
      registering the eating process on line. The patients filled out visual analogue
      scales concerning appetite and food preferences before and after the test meal.
      The feeling of fullness before meals was greater in patients on CAPD than in
      patients in the predialytic state. Transplanted patients felt less full before
      meals compared with their ratings during the dialysis period. The median total
      intake of food was lower during dialysis than after transplantation. The
      palatability of the food was rated lower during dialysis compared with the
      ratings in the uremic state. Poor appetite and low intake during dialysis is
      still a problem, but improves after transplantation.

PMID- 9159303
TI  - Dialysate cell population and cancer antigen 125 in stable continuous ambulatory
      peritoneal dialysis patients: their relationship with transport parameters.
AB  - We investigated the total cell count and cell population of the overnight
      peritoneal dialysis effluent (PDE) by flow cytometry in 76 stable continuous
      ambulatory peritoneal dialysis (CAPD) patients. The mean percentage of
      mesothelial cells and macrophages was 4.4% and 57%, respectively. A higher
      percentage of dead cells among the mesothelial cells compared with other cell
      populations in the PDE was observed. Peritoneal transport properties were studied
      in every patient by determining the dialysate to plasma ratio of creatinine
      concentration (D/P) at the fourth hour of the peritoneal equilibration test, and
      the mass transfer area coefficient of creatinine (MTACCr) or glucose. Cancer
      antigen 125 (CA125), suggested as a bulk marker for the mesothelial mass in
      stable peritoneal dialysis patients, was determined in the PDE. No correlation
      was demonstrated between CA125 and the number of mesothelial cells, lymphocytes,
      or macrophages in the PDE. A significant correlation was observed between CA125
      and different parameters of peritoneal transport (D/P and MTACCr). On the
      contrary, neither the history of peritonitis nor the duration of CAPD appeared to
      affect the CA125 concentration in the PDE. The lack of correlation between CA125
      in the PDE and the duration of CAPD may be related to the early loss of
      peritoneal transport properties as a result of the use of hypertonic dialysate in
      the majority of our patients with small-volume CAPD (3 x 2 L daily exchange). Our
      findings suggest that CA125 may not necessarily correlate well with the number of
      mesothelial cells in PDE. In patients with vanishing of the mesothelial layer,
      the measurement of CA125 (as a bulk marker for the mesothelial mass in the
      peritoneum) may reflect the change of peritoneal transport properties.

PMID- 9159304
TI  - Simultaneous removal and replacement of infected peritoneal dialysis catheters.
AB  - Infection is an important complication of peritoneal dialysis that often limits
      technique survival. Recurrent episodes of peritonitis caused by the same organism
      may be the result of catheter infection, necessitating removal. We performed 34
      single-step catheter replacement procedures in children and young adults for
      recurrent peritonitis or refractory exit site and tunnel infections. The success
      rate of the procedure was high (85%), with rare instances of intraoperative
      contamination. The presence of Staphylococcus aureus infection or exit site and
      tunnel infection were not risk factors for worse outcome. All patients continued
      on peritoneal dialysis through catheter change without requiring interval
      hemodialysis. Eighteen peritoneal dialysis catheters were replaced in a staged
      procedure with an interval off peritoneal dialysis. There was one early
      reinfection of the new catheter. Patients with Pseudomonas sp infections were
      more likely to be treated with a staged procedure; S aureus infections were
      equally likely to be managed by staged or simultaneous catheter removals.
      Simultaneous removal and replacement of infected peritoneal dialysis catheters is
      an effective management strategy when compared with two-step catheter
      replacements.

PMID- 9159305
TI  - Amino acid profile and nitric oxide pathway in patients on continuous ambulatory
      peritoneal dialysis: L-arginine depletion in acute peritonitis.
AB  - To gain insights into the amino acid metabolism and L-arginine-nitric oxide
      system, we studied 21 control continuous peritoneal dialysis (CPD) patients and
      13 patients with 15 episodes of acute peritonitis. The concentrations of amino
      acids, including L-arginine, were measured in the peritoneal dialysate and in the
      serum. The data demonstrate that patients with end-stage renal disease on CPD who
      have acute peritonitis develop L-arginine deficiency. The majority of patients
      with acute bacterial peritonitis have increased nitric oxide production as judged
      by the level of nitrites in the dialysate. The recovery from peritonitis is
      associated with a decline in nitric oxide generation. Paradoxically, there is a
      smaller subgroup of these patients that shows low nitrite levels during acute
      peritonitis. The nitrite to L-arginine ratio in the peritoneal dialysate is
      increased in patients with peritonitis, further suggesting the development of
      substrate deficiency. These findings implicate L-arginine as a conditionally
      essential amino acid in CPD patients with acute peritonitis and raise questions
      concerning the necessity of L-arginine supplementation.

PMID- 9159306
TI  - Short-term effects of blood pressure control and antihypertensive drug regimen on
      glomerular filtration rate: the African-American Study of Kidney Disease and
      Hypertension Pilot Study.
AB  - The African-American Study of Kidney Disease and Hypertension pilot study
      randomized 94 nondiabetic black men and women (mean age, 53 years; 75% male) with
      presumed hypertensive nephrosclerosis and a baseline glomerular filtration rate
      (GFR) of 25 to 70 mL/min/1.73 m2 (mean, 52.3 mL/min/1.73 m2) to blood pressure
      control at either a low mean arterial pressure (MAP) goal of < or = 92 mm Hg or a
      usual MAP goal of 102 to 107 mm Hg and an antihypertensive drug regimen that
      included either a calcium antagonist (amlodipine), a beta-blocker (atenolol), or
      an angiotensin-converting enzyme (ACE) inhibitor (enalapril). After 3 months of
      follow-up (n = 90), the mean GFR was similar (53.0 mL/min/1.73 m2 v 53.7
      mL/min/1.73 m2) to the baseline levels in participants randomized to the low MAP
      group (n = 44), whereas the mean GFR increased by 3.9 mL/min/1.73 m2 (P = 0.02)
      in participants randomized to the usual MAP group (n = 46). During the same
      period of time, the mean GFR increased significantly in participants randomized
      to the calcium channel blocker regimen (n = 28) (5.7 mL/min/ 1.73 m2; P = 0.01)
      but not in participants randomized to the beta-blocker regimen (n = 31) (1.7
      mL/min/1.73 m2; P = 0.10) or the ACE inhibitor regimen (n = 31) (1.1 mL/min/1.73
      m2; P = 0.52). Changes in GFR at 3 months were significantly different among the
      three treatment groups (P = 0.04). We conclude that the magnitude of short-term
      effects of blood pressure control and antihypertensive drug regimens on GFR
      should be considered when estimating sample size for clinical trials designed to
      evaluate the effects of these interventions on long-term changes in GFR slope.

PMID- 9159307
TI  - Familial clustering of end-stage renal disease in blacks with lupus nephritis.
AB  - The factors that determine a patient's susceptibility to specific target organ
      involvement in systemic lupus erythematosus (SLE) remain unknown. Lupus nephritis
      can be a particularly devastating complication, with an increased mortality and
      the risk of progressive renal damage resulting in end-stage renal disease (ESRD).
      This analysis was performed to determine whether renal disease aggregated in
      select families or was a sporadic complication in patients with SLE. We compared
      the family history of ESRD in 50 patients with SLE complicated by lupus nephritis
      with 37 controls who had SLE but lacked nephritis after a mean follow-up duration
      of more than 11 years. The frequency of relatives with ESRD in the lupus
      nephritis cases was compared with that in controls using Fisher's exact test
      (significance at P < or = 0.05). Fifty percent (25) of the 50 lupus nephritis
      patients were black and 50% (25) white, in contrast to 35% (13) and 65% (24) of
      the 37 lupus non-nephropathy controls, respectively. A first-, second-, or third
      degree relative with ESRD was present in 16% (eight) of the 50 lupus nephritis
      cases and in 0% of the 37 SLE non-nephropathy controls (P = 0.019, Fisher's exact
      test, two-tail). Twenty-eight percent (seven) of the 25 black patients with lupus
      nephritis had relatives with ESRD compared with 0% of the 13 black lupus non
      nephritis controls (P = 0.07). Only one of the eight relatives with ESRD had SLE
      or a collagen vascular disease. Lupus nephritis patients and the non-nephritis
      controls had similar ages (mean +/- SD: 38.5 +/- 10.0 years v 46.6 +/- 11.8
      years; P = 0.28), family sizes (6.27 +/- 2.61 first-degree relatives v 6.35 +/-
      3.25 first-degree relatives; P = 0.16), and duration of SLE (9.26 +/- 5.94 years
      v 11.35 +/- 6.43 years; P = 0.60). Familial clustering of ESRD was observed in
      black patients with SLE who had nephritis. This was unlikely to be related to
      differences in patient age, family size, or duration of SLE. This data, coupled
      with the known familial aggregation of ESRD in blacks with hypertensive and
      diabetic ESRD, supports the contention that genetic factors contribute to the
      familial clustering. The presence of relatives with etiologies of ESRD other than
      SLE suggests that there is an inherited susceptibility to progressive renal
      failure, independent of the etiology of ESRD.

PMID- 9159308
TI  - Prevalence and predictors of renal artery stenosis in patients with myocardial
      infarction.
AB  - In recent years, the importance of renovascular disease as a cause of end-stage
      renal disease has been emphasized. Among 1,788 cases autopsied during the 12-year
      period between 1981 and 1992 at the National Cardiovascular Center Hospital, we
      examined cases over 40 years of age with autopsy evidence of myocardial
      infarction to determine the prevalence and predictors of atherosclerotic renal
      artery stenosis in the atherosclerotic population. Two hundred ninety-seven
      patients remained for analysis. In this population, atherosclerotic renal artery
      stenosis was found in 35 patients (12%), and 10 of them had bilateral renal
      artery stenosis. In patients with hypertension, proteinuria, and renal
      insufficiency, renal artery stenosis was found in 19%, 39%, and 39%,
      respectively. As the number of coronary vessels with significant stenosis
      increased, the prevalence of renal artery stenosis increased. The severity of
      stenotic lesions of coronary artery was also correlated with the presence of
      renal artery stenosis. Multiple logistic regression analysis identified age,
      hypertension, proteinuria, and renal insufficiency as independent predictors of
      renal artery stenosis. Patients with hypertension, proteinuria, and renal
      insufficiency had 3.4-, 13.5-, and 4.8-fold increased risk of renal artery
      stenosis in the population with myocardial infarction. The number of coronary
      arteries with severe stenosis was also an independent predictor of renal artery
      stenosis, and had a relative risk of 2.1. These results indicated that
      atherosclerotic renal artery stenosis is common in patients with myocardial
      infarction, particularly when hypertension, proteinuria, or renal insufficiency
      is present. The presence of severe multivessel coronary artery disease suggests a
      higher incidence of renal artery stenosis.

PMID- 9159309
TI  - Increased living donor volunteer rates with a formal recipient family education
      program.
AB  - We have generally encouraged living donation among our kidney recipients.
      However, an examination of our clinical practice revealed inconsistencies in the
      depth and content of information transmitted to kidney recipient families
      regarding living donation. We therefore initiated a structured education program,
      including an educational video, to ensure that all recipient families would
      receive a similar exposure to a standard block of information. After the program
      had been functioning for over a year, we compared the living donor (LD) volunteer
      rates between the 3-year period before (BEFORE) and the 18 months after (AFTER)
      initiation of the formal education program. There were 1,363 patients registered
      on our kidney transplantation waiting list during the 54-month study period (757
      white [56%] and 580 black [43%]). We found that 33.4% of the kidney transplant
      candidates in the period BEFORE the LD education program had at least one
      potential LD tissue typed, compared with 39.4% in the period AFTER starting the
      program (P = 0.03). The increase in the proportion of patients with potential
      donors was greatest among the black (P < 0.05) and elderly (P < 0.01)
      registrants, which were the groups with the lowest volunteer rates before the
      program began. Among the registrants with at least one potential donor, the
      percentage of registrants who ultimately received an LD transplant was highly
      correlated with the number of donors (R = 0.98). The rate of LD kidney
      transplantation was significantly higher (P = 0.02) for the patients referred in
      the period AFTER initiation of the LD education program compared with the period
      BEFORE the program. The 1- and 3-year graft survival rates for the 170 LD
      transplants performed in these patients were 96.9% and 93.2%, respectively. These
      were significantly better than the corresponding 83.9% and 71.4% rates for the
      341 kidney transplants from cadaver donors in these registrants (P < 0.001).
      Black recipients of LD transplants had graft survival rates comparable to whites;
      the 3-year graft survival rate for LD transplants was 93.9% in whites and 90.6%
      in blacks (P = NS). We conclude that living kidney donor volunteer rates can be
      improved by a formal family education program, especially for subgroups of
      patients with low volunteer rates. A substantial benefit is derived by black
      patients, who generally experience low graft survival rates with cadaver-donor
      kidneys. A local formal LD education program is a useful adjunct to national
      organ donation campaigns.

PMID- 9159310
TI  - No trend toward a spontaneous improvement of hyperparathyroidism and high bone
      turnover in normocalcemic long-term renal transplant recipients.
AB  - Although hyperparathyroidism is a common feature in renal transplant recipients,
      the long-term course of parathyroid hormone (PTH) secretion in these patients is
      not well established, and the actual contribution of PTH to posttransplant bone
      disease remains incompletely understood. Therefore, we studied calcium-regulating
      hormones and serum osteocalcin, as a marker of bone remodeling, in 82
      normocalcemic renal transplant recipients with good renal function who had
      received a graft 6 to 73 months previously and in 82 healthy subjects matched for
      age and sex. In all subjects, fasting serum and 24-hour urinary samples were
      collected. The transplant recipients had excessive PTH secretion (serum PTH, 6.9
      +/- 0.5 pmol/L in recipients v 3.0 +/- 0.1 pmol/L in healthy subjects; P < 0.001)
      and high bone turnover (osteocalcin, 16.6 +/- 0.8 microg/L v 8.0 +/- 0.3
      microg/L; P < 0.001). (Values are mean +/- SEM.) In addition, transplant
      recipients had a slightly higher ionized calcium than the healthy subjects,
      providing definite evidence of an inappropriate PTH secretion in renal transplant
      recipients. Furthermore, in subgroups of 25 recipients and 25 healthy controls
      matched for creatinine clearance, the results superimposed those obtained in the
      whole groups, suggesting that excessive PTH secretion and high bone turnover in
      renal transplant recipients did not merely reflect the moderately reduced renal
      function of some recipients. In the whole group of transplant recipients, PTH
      correlated positively with osteocalcin (r = 0.40; P < 0.001), suggesting that PTH
      contributes at least partly to posttransplant bone disease. Conversely, there was
      no correlation between serum PTH or osteocalcin and the delay from grafting.
      Therefore, our results provide no evidence for a spontaneous improvement of
      either persistent hyperparathyroidism or high bone turnover in normocalcemic long
      term renal transplant recipients.

PMID- 9159311
TI  - Polyomavirus-induced interstitial nephritis in two renal transplant recipients:
      case reports and review of the literature.
AB  - We present two case reports of renal polyomavirus infection leading to renal
      allograft dysfunction, review the literature of this entity, and discuss the role
      of specific immunosupressives. Histologically, the virus caused an interstitial
      infiltrate composed of plasma cells and lymphocytes, interstitial fibrosis, and
      tubular atrophy. Viral inclusions were seen within tubular cells on light
      microscopy. Electron microscopy showed viral particles of 40 to 50 nm in a
      characteristic paracrystalline array. Both patients had been on FK-506-based
      immunosuppression. In both patients, the virus appeared to clear histologically
      and renal function stabilized when the patients were converted to cyclosporine
      based immunosuppression. Contrary to prior reports, our patients have not lost
      their grafts and continue to have stable, albeit reduced, graft function at 2.5
      years and 4.5 years following the initial diagnosis of renal polyomavirus
      infection.

PMID- 9159312
TI  - Biochemical aberrations in a dialysis patient following parathyroidectomy.
AB  - Renal osteodystrophy is a common problem in patients with end-stage renal
      disease. Severe secondary hyperparathyroidism unresponsive to an intensive
      regimen of diet, phosphate binders, and calcitriol therapy is an indication for
      surgical parathyroidectomy. Certain unique postoperative electrolyte aberrations
      are seen after parathyroidectomy, including severe hypocalcemia and
      hypophosphatemia (hungry bone syndrome), as well as hyperkalemia. Identifying the
      patient at high risk for developing these electrolyte abnormalities will
      facilitate perioperative and postoperative management.

PMID- 9159313
TI  - The efficacy of exit site povidone-iodine ointment in the prevention of early
      peritoneal dialysis-related infections.
AB  - Infections are the main complications of peritoneal dialysis, and currently there
      is no established method for prevention. A prospective, randomized, single-blind
      study was performed to evaluate the efficacy of regular application of povidone
      iodine ointment at the catheter site (during the entire time on the study) in
      peritoneal dialysis. One hundred twenty patients were randomized; three were
      excluded for not completing the study. Sixty-one patients received application of
      povidone-iodine and 56 patients received standard care. Povidone-iodine ointment
      was effective in delaying infectious complications, with a lower proportion of
      treated patients having infections (exit site and peritonitis) within 140 days of
      starting dialysis compared with the controls (P = 0.04, Wilcoxon test). This
      protective benefit was lost after 140 days on dialysis. Staphylococcus aureus
      infections developed in only two (3.3%) of the treated patients compared with 10
      (21.4%) of the controls (P = 0.009), despite the higher rate of S aureus nasal
      carriage in the treated group (22 of 61 patients [36%] v 14 of 56 patients
      [25%]).

PMID- 9159315
TI  - Calciphylaxis in a patient with Crohn's disease in the absence of end-stage renal
      disease.
AB  - Calciphylaxis is a rare and life-threatening condition of progressive cutaneous
      necrosis secondary to small and medium-sized vessel calcification previously
      described in patients with end-stage renal disease and hyperparathyroidism. Early
      diagnosis may be important in improving the poor outcome in these patients since
      early intervention may forestall the development of life-threatening
      complications. We describe a patient with Crohn's disease complicated by short
      bowel syndrome and modest renal insufficiency (not requiring renal replacement
      therapy) who developed calciphylaxis. It appears that longstanding Crohn's
      disease and the short-bowel syndrome accelerated the development of calciphylaxis
      as the chronic renal disease was not end stage. Considering the possibility of
      calciphylaxis in this setting may avoid delaying the diagnosis and its
      consequences.

PMID- 9159314
TI  - Resistance to recombinant erythropoietin in a hemodialysis patient with
      heterozygous hemoglobinopathy J-Meinung.
AB  - The mechanism of resistance to recombinant human erythropoietin (EPO) in
      hemodialysis patients with hemoglobinopathy is not yet fully understood. Poor
      responses to EPO have been reported in anemic dialysis patients with sickle cell
      disease and thalassemia. We present the first case of a hemodialysis patient with
      EPO resistance and hemoglobin J-Meinung, which is initially found by hemoglobin
      electrophoresis and finally proven by molecular genetic analysis. Additionally,
      the patient was diagnosed as having chronic active hemolysis with hallmarks of
      splenomegaly, an increased serum bilirubin and reticulocyte index, and a reduced
      haptoglobin level. We discuss the possible mechanisms and proper treatment
      options in such patients with a poor response to EPO.

PMID- 9159316
TI  - Kidneys on vacation: the notion of renal work and the introduction of
      nonpharmacological therapies.
AB  - "Wisdoms of today become the follies of tomorrow," remarked none other than Franz
      Volhard, who first classified renal disease. In earlier times, nephrologists
      relied less on controlled randomized prospective trials and more on common sense.
      One such notion was the idea that kidneys could be "rested" by requiring them to
      make less urine. Particularly in Germany early in this century, patients with
      chronic renal disease were advised to go to Assuan in Egypt, where the warm sunny
      weather and low humidity decreased their urinary output. Thus, a "vacation" was
      prescribed for sick kidneys, and indeed, early in his career Volhard also
      supported this notion. In a small but excellent study, Loewy, Wohlgemuth, Bickel,
      and Schweitzer concluded that a decreased urinary output, rather than decreasing
      renal work, would require a considerable increase in concentration of excreted
      solutes, a task that patients with renal insufficiency would not be likely able
      to meet. These findings, as well as the observation that renal patients often
      failed to return from Egypt, caused Volhard to change his mind.

PMID- 9159317
TI  - The changing supply of renal physicians.
AB  - In 1993, there were 4,355 active, postresident physicians in the United States
      who, according to the American Medical Association (AMA) Physician Masterfile,
      had their primary specialty in either adult nephrology or pediatric nephrology.
      These renal physicians constituted 0.8% of the active postresident physician
      population, and there were 1.67 renal physicians for every 100,000 people in the
      United States. The population of renal physicians has grown at a significantly
      greater rate than the physician population as a whole. The number of renal
      physicians increased more than 10-fold between 1970 and 1993, and it increased by
      19% between 1990 and 1993. In recent years, the growth of the renal physician
      population has been bolstered by the large number of new international medical
      graduates (IMGs) entering the United States, who have entered nephrology at a
      much higher rate than entering US medical graduates (USMGs). The future growth of
      the renal physician population will be determined by a wide variety of factors,
      including future trends in specialty selection and whether policies are
      implemented to reshape the physician workforce. The projection analysis of the
      future supply of adult nephrologists considers three different scenarios. First,
      if the production of new nephrologists remains at status quo, the supply of adult
      nephrologists will increase 101% between 1993 and 2010. However, it is possible
      that the number of entrants into the adult nephrologist population will increase
      because of the large influx of IMGs in US residency programs in recent years. If
      new IMGs continue to enter adult nephrology at their current rates and if this
      heightened level of entry is sustained, the supply of adult nephrologists will
      increase 134% between 1993 and 2010. Finally, if proposals are implemented to
      reduce the number of first-year residency positions to 110% of the number of new
      graduates of US medical schools and to raise the proportion of new physicians
      entering primary care to 50%, the supply of adult nephrologists will increase 62%
      between 1993 and 2010. The demand for nephrologists' services is likely to grow
      in the near future. The prevalence rate of end-stage renal disease (ESRD) more
      than doubled between 1984 and 1993, and a continuation of this trend will expand
      the need for more nephrologists. The long-term growth of the ESRD population will
      also be sustained, to some extent, by the aging of the US population, because the
      prevalence of ESRD is relatively high in the older age categories. However, long
      term increases in the demand for nephrologists may be restricted by the growth of
      managed care, the use of nonphysician providers, and the implementation of other
      cost-cutting measures that impact the delivery of services to the ESRD
      population.

PMID- 9159318
TI  - Acute renal failure in the 21st century: recommendations for management and
      outcomes assessment.
AB  - Acute renal failure (ARF) remains a common and potentially devastating disorder
      affecting as many of 5% of all hospitalized patients, with a higher prevalence in
      patients in critical care units. ARF is more frequently observed in the setting
      of multiorgan dysfunction syndrome (MODS) and in elderly patients with complex
      disease, where mortality is high. Numerous technical advances have not yet
      impacted favorably on this high mortality rate. This report summarizes
      recommendations from participants at the National Institutes of Health
      Conference: "Acute Renal Failure in the 21st Century," May 6 to 8, 1996, in
      Bethesda, MD. The focus is on categorizing recent clinically relevant
      developments in the field and on identification of new research initiatives to
      transfer a new body of knowledge derived from fundamental studies and laboratory
      investigation to the management of ARF in the new millennium. The development of
      a multicenter database through cooperative multicenter studies is advocated.
      Future studies should define the appropriate outcome measures to assess and
      emphasize the impact of hemodynamic monitoring, adjunctive agents, and adequacy
      and modality of renal replacement therapy on outcomes in ARF.

PMID- 9159319
TI  - The influence of dietary salt on the antiproteinuric effect of calcium channel
      blockers.

PMID- 9159320
TI  - A 51-year-old woman with nephrotic syndrome, hematuria, and renal insufficiency.
AB  - This case illustrates the utility of all modalities of the renal biopsy in
      arriving at a correct diagnosis in an adult patient with nephrotic syndrome.
      Unlike the clinical situation in children, where minimal change disease is
      presumed to underlie the nephrotic syndrome unless the patient shows steroid
      resistance, the list of differential diagnosis of nephrotic syndrome in the adult
      is lengthy. The renal biopsy is essential in establishing the specific diagnosis.
      We discuss the diagnostic approach in an adult patient with a relatively uncommon
      disease causing the common manifestations of nephrotic syndrome, hematuria and
      renal insufficiency.

PMID- 9159321
TI  - Hypertension in the hemodialysis population.

PMID- 9159322
TI  - Proximal calciphylaxis in four insulin-requiring diabetic hemodialysis patients.

PMID- 9159323
TI  - Cyclosporine as cause of thrombotic microangiopathy after renal transplantation.

PMID- 9159324
TI  - Ovarian cancer screening and psychosocial issues: relevance to clinical practice.

PMID- 9159325
TI  - Psychological impact of screening for familial ovarian cancer: reactions to
      initial assessment.
AB  - OBJECTIVES: To assess the psychological impact on women attending a familial
      ovarian cancer screening clinic. STUDY METHODS: 157 women referred for screening
      completed an investigator designed questionnaire, the Spielberger State Trait
      Anxiety Scale and the Centre for Epidemiological Studies Depression Scale prior
      to the screening interview and an eight-item questionnaire post-assessment.
      RESULTS: 95.4% saw the screening as valuable. Thirty-one point four percent of
      all patients scored about the cutoff point for depression. Sixteen percent
      exhibited high levels of anxiety. Fifty-six point four percent of patients
      accurately perceived their risk. Twenty-one point five percent of those who
      accurately perceived themselves as being at high risk had high anxiety and 40.6%
      reported significant depressive symptoms. Of the 26.5% of patients who
      overestimated their risks, 40.0% reported significant depressive symptoms and
      22.6% were anxious. Of the 17.1% who minimized their risk, none were anxious
      (0.0%), and only 15.8% were depressed. CONCLUSION: Attendees at a familial
      ovarian cancer screening clinic may have high levels of depression and anxiety.

PMID- 9159326
TI  - Papillary serous and clear cell type lead to poor prognosis of endometrial
      carcinoma in black women.
AB  - OBJECTIVE: To investigate the significance of race and histologic type as
      prognostic factors in endometrial carcinoma. METHODS: We conducted a
      retrospective review of the medical records of all patients diagnosed with
      endometrial cancer from 1982 to 1995. Patients' clinical and pathologic
      characteristics were analyzed. RESULTS: The sample consisted of 401 patients,
      59.9% (N = 229) were blacks and 40.1% (N = 153) were non-blacks. The mean age was
      63.7 +/- 11.6 years. The histologic subtypes of endometrial carcinoma included
      346 endometrioid (86.3%), 42 papillary serous (10.5%), and 13 clear cell (3.2%)
      adenocarcinomas. We found 79% of endometrioid adenocarcinomas were stage I or II
      compared to 26% of papillary serous tumors and 58% of clear cell carcinomas (P <
      0.01). Eighty-eight percent of patients with papillary serous and 77% of patients
      with clear cell cancers were black (P < 0.01). Within each stage, patients were
      treated similarly irrespective of cell type or race. Five-year survival for
      endometrioid, papillary serous and clear cell adenocarcinomas was 69, 18, and
      25%, respectively (P < 0.01). Black women had poorer 5-year survival (56%) than
      non-black women (71%). In multivariate analyses using age, stage, race, and
      histology, only stage and histology were independent risk factors for survival.
      CONCLUSIONS: Patients with papillary serous and clear cell endometrial cancer
      were more likely to be black, present at an advanced stage of disease, and have
      poor survival compared to patients with endometrioid adenocarcinoma. This may
      help to explain the poorer survival reported in blacks with endometrial cancer.

PMID- 9159327
TI  - Invasive cancer of the vulva.
AB  - This study comprised 328 patients with histologically confirmed primary invasive
      vulvar cancer, treated between 1948 and 1994. It retrospectively analyzes
      survival rates in relation to various prognostic factors. Mean and median age at
      diagnosis was 69 years (n = 328). The patients had experienced various symptoms
      on an average of 16.3 months prior to diagnosis (median, 6 months). Common
      presenting symptoms were pruritus, smarting pain, and vulvar tumor. Three hundred
      patients (91.5%) had squamous cell carcinomas and they were classified according
      to stage and tumor differentiation as follows: Stage I, 106 (35%); Stage II, 111
      (37%); Stage III, 44 (15%); and Stage IV, 39 (13%); well differentiated, 107
      (36%); moderately differentiated, 129 (43%); poorly or undifferentiated, 45
      (15%); and in 19 cases (6%), tumor differentiation was not available. In 277
      (92%) patients the primary treatment was surgical; 189 (63%) patients
      additionally received radiotherapy and 13 (4%) patients were also given
      chemotherapy. In 18 patients (6%), the primary treatment was radiotherapy and 5
      of these also received chemotherapy. Two patients were given primary chemotherapy
      and three patients received no treatment. Median survival rate was not reached
      during the observation time for Stage I. At 10 years observation time survival
      rate was 85% in this stage. Median survival times for Stages II, III, and IV were
      reached at 128, 20, and 8 months observation time, respectively. The median
      survival time in patients with well-differentiated tumors was 152 months;
      corresponding figures for moderately differentiated and poorly differentiated
      tumors were 114 and 74 months, respectively. The most important prognostic
      factors in this study were tumor stage (P < 0.00001), patient age (P < 0.01), and
      tumor differentiation (P = 0.02).

PMID- 9159328
TI  - p53 and HER-2/neu overexpression in ovarian borderline tumors.
AB  - OBJECTIVE: To study p53 and HER-2/neu expression in borderline ovarian tumors
      (BLOT) by assessing their frequency, coexpression, and relationship to histologic
      type, FIGO stage, tumor recurrence, and survival. METHODS: Forty-two patients
      with confirmed BLOT (25 serous, 13 mucinous, and 4 seromucinous) were followed
      for 1.5 to 14 years (mean, 6.3). Thirty (71%) patients had FIGO stage I and 12
      (29%) had FIGO stage III disease. Paraffin-embedded sections from the 42 BLOT, 5
      normal ovaries, and 10 benign ovarian cystadenomas were stained using monoclonal
      antibodies against human p53 (DAKO-p53, DAKO, Denmark) and HER-2/neu (C-erB-2,
      Triton, Parkway, CA). Positive staining was semiquantitated depending on the
      number of positively stained tumor cells. p53 and HER-2/neu overexpressions were
      correlated to each other, to histologic subtype, stage, tumor recurrence, and
      survival. RESULTS: None of the patients had tumor recurrence. The 5- and 10-year
      disease-free survival was 100%. None of the normal ovaries or ovarian
      cystadenomas demonstrated overexpression of p53 or HER-2/neu. Ten (24%) BLOT
      demonstrated overexpression of p53 and 9 (21%) demonstrated overexpression of HER
      2/neu. HER-2/neu overexpression was significantly greater in stage III than in
      stage I tumors (P = 0.0157). Seromucinous BLOT demonstrated significantly greater
      p53 overexpression compared with other histologic subtypes (P = 0.030).
      Coexpression of p53 and HER-2/neu occurred in 4 patients (9.5%). There was no
      significant correlation between the overexpression of p53 and HER-2/neu (P =
      0.180) and no significant relationship between p53 and HER-2/neu overexpression
      and the presence of microinvasion, ability to perform optimal cytoreductive
      surgery, tumor recurrence, or survival. CONCLUSIONS: p53 and HER-2/neu
      overexpression occurred in about 20-25% of BLOT overall and more commonly in
      seromucinous and advanced stage tumors. Coexpression occurred in 9.5% of the
      cases with no significant correlation between the expression of p53 and HER
      2/neu.

PMID- 9159329
TI  - Uterine leiomyosarcoma has deregulated cell proliferation, but not increased
      microvessel density compared with uterine leiomyoma.
AB  - OBJECTIVE: To investigate the differences of biological aggressiveness in terms
      of proliferating cell nuclear antigen (PCNA) expression, cell proliferation, and
      microvessel density between uterine leiomyosarcoma and leiomyoma. STUDY DESIGN:
      All patients with uterine leiomyosarcoma undergoing surgery at National Cheng
      Kung University Hospital were eligible. Forty-four patients with uterine myoma
      were also studied as the benign counterpart. The paraffin-embedded slides were
      stained with hematoxylin and eosin to confirm the presence of tumor and to
      quantitate mitoses, PC 10 for measurement of PCNA expression, MIB 1 for
      measurement of cell proliferation, and factor VIII for quantitation of
      microvessel density. The immunohistochemical findings of the slides were
      correlated with clinocopathologic findings of the patients, and the data were
      analyzed by either chi2 or unpaired t test. RESULTS: Six patients with uterine
      leiomyosarcoma and 44 patients with uterine leiomyoma were studied. Statistically
      significant higher mean levels of PCNA and MIB 1 were observed in uterine
      leiomyosarcoma compared with those of uterine myoma (for PCNA expression, P =
      0.0001; for MIB 1, 11.61 +/- 11.42% vs 0.45 +/- 0.21%, P < 0.0001). No
      significant difference of microvessel density was observed between these two
      groups (65.73 +/- 48.62 vs 41.97 +/- 28.20, P = 0.084). Among the six patients
      with leiomyosarcoma, two patients with a higher percentage of MIB 1-positive
      tumor cells died of recurrent disease. In contrast, two patients with lower MIB 1
      counts were disease-free for 3 years or more. CONCLUSION: Deregulated cell growth
      in uterine leiomyosarcoma may account for the biological aggressiveness of this
      tumor. Furthermore, the percentage of MIB 1-positive tumor cells seems to be
      associated with the prognosis or extent of uterine leiomyosarcoma.

PMID- 9159330
TI  - Retinoblastoma protein expression in endometrial hyperplasia and carcinoma.
AB  - The retinoblastoma (RB) gene was the first defined tumor suppressor gene. While
      originally described in retinoblastoma, more recently alterations in RB have been
      described in a number of other human neoplasms and there has been a suggestion
      that alteration of RB may play a significant role in the development of
      endometrial carcinoma. We examined RB protein expression by immunohistochemistry
      in a series of cases including normal endometrium, endometrial hyperplasia, and
      endometrial carcinoma. A relatively homogeneous pattern of staining was observed
      in proliferative endometrium, while weak or absent reactivity was noted in
      secretory endometrium. A heterogeneous pattern of reactivity was observed in
      10/10 cases of hyperplasia, 66/70 cases of endometrial adenocarcinoma, and 7/7
      cases of uterine carcinosarcoma. An altered pattern of reactivity was observed in
      the remaining 4/70 cases of adenocarcinoma. All of the cases with altered
      reactivity were high grade neoplasms. We conclude that alteration of RB protein
      expression is uncommon in endometrial adenocarcinoma and when it does occur, it
      may represent a late event in carcinogenesis.

PMID- 9159331
TI  - Malignant mixed mesodermal ovarian tumor treatment and prognosis: a 20-year
      experience.
AB  - Mixed mesodermal sarcoma of the ovary is a rare clinical entity. To review the
      epidemiology, prognostic factors, and treatment results related to primary
      ovarian sarcoma at our center, a retrospective chart review of all patients
      referred for ovarian cancer was carried out from 1974 to 1994. Cases with
      confirmed pathologic diagnosis of primary mixed mesodermal ovarian sarcomas were
      selected, forming the present study group. Thirty-six charts were identified. The
      median age at presentation was 67.5 years. Findings at laparotomy demonstrated
      extraovarian metastasis in 33/35 patients. Total abdominal hysterectomy and
      bilateral salpingo-oophorectomy +/- omentectomy were performed in 34 patients,
      with 22 patients left with macroscopic residual disease after surgery. Follow-up
      adjuvant chemotherapy consisting of cisplatin and doxorubicin was administered to
      29/36 patients. Follow-ups ranged from 1 to 11 years with a median of 2 years. As
      with epithelial ovarian cancer, residual disease after initial surgery is an
      important prognostic factor. Thirteen patients had a second-look laparotomy. Five
      patients were positive for disease. Eight patients, one of whom recurred, were
      histologically negative. The patients with positive second-look findings, as well
      as all those who recurred clinically, subsequently died within 12 months despite
      trials with different second-line chemotherapeutic agents. Survival analysis
      showed a median survival of 3 years among patients treated with combination
      cytotoxic chemotherapy. Primary ovarian sarcomas make up about 2-3% of all
      ovarian cancer cases seen in our center. These are often very aggressive tumors
      with widespread metastasis at the time of presentation, making optimal tumor
      debulking difficult. The combination of cisplatin and doxorubicin appears to have
      activity resulting in a survival of 35% at 5 years. Second-look surgery offers
      little helpful information on the management of these tumors.

PMID- 9159332
TI  - Serum CA-125 screening for ovarian cancer in patients with dermatomyositis.
AB  - Ovarian cancer is the most overrepresented malignancy diagnosed in women with
      dermatomyositis. Unfortunately, screening with pelvic examination rarely detects
      this cancer prior to the development of metastatic disease. Our objective was to
      examine the use of serum CA-125 antigen levels in screening patients with
      dermatomyositis for ovarian cancer. A single blinded, case-control study was
      conducted in our institution of CA-125 levels in 14 women diagnosed with
      dermatomyositis between 1986 and 1993, 4 of whom subsequently developed ovarian
      cancer. In the 4 patients who developed ovarian cancer ("cases"), CA-125
      determinations were performed on serum stored 5 to 19 months prior to the
      diagnosis of ovarian cancer. In the remaining 10 patients ("controls"), serum was
      drawn for CA-125 level determination at the time of the study, and simultaneous
      gynecologic and endovaginal ultrasound examinations were performed to exclude
      clinical evidence of ovarian cancer. All CA-125 serum measurements were performed
      simultaneously by a technician blinded to disease status using one diagnostic
      kit. CA-125 was found to be elevated in 2 patients with ovarian cancer (on serum
      obtained 5 and 13 months prior to the date of diagnosis of ovarian cancer) and in
      none of the control patients without clinical or ultrasound evidence of ovarian
      cancer (relative risk = 20, 95% confidence interval = [0.64, 666]). In these 14
      patients, the sensitivity of CA-125 elevation for detection of ovarian cancer was
      50%, and specificity was 100%. Serum CA-125 screening for ovarian cancer in
      patients having dermatomyositis may be useful; however, prospective studies are
      needed to confirm this and to determine the effect of screening on cancer stage
      at diagnosis and long-term survival.

PMID- 9159333
TI  - Three-dimensional hysterosonography for the study of endometrial tumors:
      comparison with conventional transvaginal sonography, hysterosalpingography, and
      hysteroscopy.
AB  - We studied endometrial thickness and homogeneity in 36 patients with
      postmenopausal bleeding using three-dimensional ultrasound following distention
      of the uterine cavity with a sterile saline solution (3D-SHSG). Results with 3D
      SHSG were compared with findings using transvaginal sonography, transvaginal
      sonohysterography, transvaginal color Doppler, and hysteroscopy. Sixteen patients
      (including three on tamoxifen) were undergoing hormone therapy at the time when
      they were studied. Visualization of the uterine cavity and of endometrial
      thickness was better with 3D-SHSG than with any of the other ultrasound
      techniques. The results with 3D-SHSG corresponded to the findings observed with
      hysteroscopy. Three-dimensional SHSG seems to improve ultrasound determination of
      myometrial and cervical invasion in cases of endometrial adenocarcinoma.

PMID- 9159334
TI  - Enhancement of 131I-mediated cytotoxicity by caffeine.
AB  - In cell culture, caffeine has been shown to enhance the lethality of DNA-damaging
      agents including ultraviolet rays, X-irradiation, and alkylating agents. We have
      previously reported a Phase I clinical trial demonstrating the feasibility of
      intraperitoneal radioimmunotherapy in patients with refractory ovarian cancer
      using 131I-labeled monoclonal antibody OC125. We are now exploring the
      possibility of using caffeine to enhance the toxicity of 131I-irradiation in
      target cells. As an in vitro model we tested this hypothesis using Chinese
      hamster ovary (CHO) cells exposed to 131I-labeled human serum albumin at various
      doses (4 to 70 microCi/ml) for 24 hr followed by 24 hr of incubation with
      caffeine. Cytotoxicity was measured by clonogenic survival and a nuclear
      fragmentation assay. The results show that caffeine, at a concentration of 7.7
      mM, significantly enhances the cytotoxicity of 131I-irradiation.

PMID- 9159335
TI  - Decrease in tumor volume and histologic response to intraarterial neoadjuvant
      chemotherapy in patients with cervical and endometrial adenocarcinoma.
AB  - Our purpose was to evaluate the utility of clinicopathological and biological
      markers prior to treatment in predicting the immediate response to chemotherapy
      in cervical and endometrial adenocarcinomas. Twelve patients with locally
      advanced cervical adenocarcinomas and 16 patients with endometrial
      adenocarcinomas received intraarterial neoadjuvant chemotherapy (NAC) consisting
      of cisplatin and doxorubicin before surgical resection. The decrease in tumor
      volume on magnetic resonance imaging (MRI) ([tumor volume before NAC - tumor
      volume after NAC]/tumor volume before NAC x 100) and the histologic response to
      NAC were assessed. Five factors prior to NAC (nuclear grade, pretreatment tumor
      volume, PCNA index, p53 protein expression, and DNA ploidy) were analyzed for
      correlation with the decrease in tumor volume and histologic response in cervical
      and endometrial adenocarcinoma, respectively. In cervical adenocarcinoma,
      patients with higher PCNA index tumor (> or = 40.2%) showed a significantly
      greater decrease in tumor volume than those with lower PCNA index (P < 0.05). In
      patients with endometrial adenocarcinoma, those with a smaller tumors (< 30.3
      cm3) showed a significantly greater decrease than those with a larger tumors (P <
      0.001). Tumors with higher PCNA index (> or = 31.5%) and negative p53 protein
      expression appeared to respond better than other tumors, but the difference was
      not statistically significant. Nuclear grade and DNA ploidy were not correlated
      with decrease in tumor volume either in cervical adenocarcinoma or in endometrial
      adenocarcinoma. Four cases of effective histologic response (2 complete responses
      [no microscopic residual tumor] and 2 marked responses [no macroscopic residual
      tumor]) were noted only in patients with endometrial adenocarcinoma who had a
      smaller tumor, higher PCNA index, and negative p53 protein expression.
      Pretreatment tumor volume and PCNA index were the only significant predictive
      factors (P < 0.05). Results suggest that the PCNA index in cervical and
      endometrial adenocarcinomas and the pretreatment tumor volume in endometrial
      adenocarcinoma appeared to be potentially useful in predicting the immediate
      response to the chemotherapy.

PMID- 9159336
TI  - Interferon-gamma enhances susceptibility of cervical cancer cells to lysis by
      tumor-specific cytotoxic T cells.
AB  - Recently we have demonstrated that tumor-specific cytotoxic T lymphocytes (CTLs)
      can be activated by cervical carcinoma cells expressing the costimulatory
      molecule CD80, which may be used as a therapeutic vaccine for patients with
      cervical cancer. For activated CTLs to be effective, appropriate amounts of MHC
      class I expression are required on target tumor cells. In this study, we found
      that some cervical carcinoma cells expressed only low levels of MHC class I and
      adhesion molecules such as CD54. We further demonstrated that tumor cells (CaSki
      and SiHa) expressing low levels of MHC class I were more resistant to lysis by
      specific CTLs than tumor cells (HeLa) expressing high levels of MHC class I.
      Treatment of CaSki or SiHa cells with interferon-gamma resulted in an increased
      expression of MHC class I, MHC class II, and CD54. Expression of CD58 and CD80
      was not up-regulated or induced. Treatment of the tumor cells with interferon
      gamma significantly enhanced the lysis of the tumor cells by specific CTLs which
      had been activated by the respective CD80-expressing tumor cells. The enhancement
      of cytolysis could be blocked by monoclonal antibodies to MHC class I and CD54,
      but not by that to MHC class II. Furthermore, we found that interferon-gamma
      induced apoptosis in cervical carcinoma cells but not in tumor-specific CTLs.

PMID- 9159337
TI  - Increased expression of LH/hCG receptors in endometrial hyperplasia and carcinoma
      in anovulatory women.
AB  - Endometrial hyperplasias and carcinomas are well documented to occur in
      anovulatory women with or without polycystic ovarian syndrome (PCO), which is
      characterized by hypersecretion of luteinizing hormone (LH). Although
      overexpression of LH/human chorionic gonadotropin (hCG) receptors has been
      demonstrated in endometrial carcinomas, whether LH/hCG receptors are also
      expressed in the endometrial hyperplasias is not known. In this study, the
      expression of LH/hCG receptors as well as that of progesterone receptors (PR) was
      analyzed by immunohistochemistry in 20 cases of normal endometria and 24 cases of
      endometrial hyperplasia and carcinoma (9 simple hyperplasias, 6 complex
      hyperplasias, 6 atypical hyperplasias, and 3 well-differentiated carcinomas).
      Fifteen of the 24 patients were 40 years old or younger, presumably anovulatory
      by BBT chart. Serum levels of LH, follicular stimulating hormone (FSH),
      prolactin, estradiol, and testosterone were measured by radioimmunoassay.
      Expression of LH/hCG receptors was detected in 19 of the 21 hyperplasias with a
      relatively stronger staining intensity in the glandular cells of complex or
      atypical hyperplasia as compared with normal endometrial glands or simple
      hyperplasia. In addition, all of the 3 carcinoma specimens showed stronger
      expression of LH/hCG receptors compared with normal endometria. The expression of
      LH/hCG receptors was well correlated with the staining for PR. Hormonal assay
      revealed 3 women to have the typical endocrinological profile of PCO. These
      findings suggest that the increased expression of LH/hCG receptors is a feature
      of endometrial hyperplasia and carcinoma developing in younger anovulatory women
      including those with PCO.

PMID- 9159338
TI  - Early adenocarcinoma of the uterine cervix.
AB  - The purpose of this study was to evaluate the prognostic significance of the
      tumor depth, horizontal spread, and volume in early cervical adenocarcinoma while
      excluding adenocarcinoma in situ. Thirty cases who had been treated at our
      institution having cervical adenocarcinoma with a tumor depth of less than 5 mm
      were clinicopathologically reviewed. The volumes were estimated based on the
      portion with the largest tumor surface area by multiplying three dimensions:
      depth, horizontal spread, and a third dimension. The third dimension was
      calculated by the method of Burghardt to be 1.5 times the largest measured depth
      or spread. Two of the 30 patients recurred in the vagina at 18 and 163 months
      after the initial operation; the former patient died of disease 87 months
      postoperatively. The remaining 28 patients are all doing well without recurrence
      (range of follow-up from 24 to 232 months; median 79 months). No pelvic or
      paraaortic lymph node metastases were seen in 25 and 22 cases, respectively. None
      of the 21 cases with a lesion measuring less than 3 mm in depth had recurrence.
      On the other hand, 1 of 23 with a tumor volume up to 500 mm3 had recurrence. The
      estimated 5-year progression-free survival rates for patients with cervical
      adenocarcinoma with a depth of less than 3 mm and those with a depth of more than
      3 mm were 100 and 88.89%, respectively (P = 0.116). The depth of stromal invasion
      may therefore be a good predictor of lymph node metastasis and recurrence in
      early cervical adenocarcinoma.

PMID- 9159339
TI  - Correlating cone biopsy histology with operative indications.
AB  - OBJECTIVE: To correlate operative indications for and histologic findings of cold
      knife cone biopsy since introduction of the Bethesda system for classification of
      cervical cytology. METHODS: Patients undergoing cold knife conization of the
      cervix at adjacent urban medical centers were identified from operating logs.
      Data on indication and outcome were tabulated retrospectively for 294 women.
      RESULTS: Cone biopsy indications were sometimes multiple and included dysplastic
      or malignant endocervical curettage (ECC) in 66%, inadequate colposcopy in 48%,
      cytologic:histologic discrepancy in 16%, and suspicion of invasive cancer on
      biopsy in 1% of cone biopsies. For 8% of patients, none of these indications were
      found. The respective proportions of women with benign findings or atypical, low
      grade dysplasia, high-grade dysplasia, or cancer was 16, 15, 65, and 3% for
      positive ECC, 26, 16, 54, and 4% for inadequate colposcopy, 22, 17, 59, and 0%
      for discrepancy, and 0, 0, 100, and 0% for suspicion of cancer on cytology.
      Outcomes were significantly worse among women with positive ECC (OR = 2.1, P =
      0.006). CONCLUSIONS: The likelihood of identifying high-grade lesions in cone
      biopsy specimens is high, especially among women with a positive ECC, but the
      risk of cancer is low.

PMID- 9159340
TI  - Is OVX1 a suitable marker for endometrial cancer?
AB  - The single most common cause leading to the diagnosis of endometrial cancer is
      postmenopausal bleeding. Although most patients with early-stage disease (FIGO
      stage I and II) can be cured, prognosis worsens considerably with increasing
      stage. While serum CA 125 levels are elevated only in a significant proportion of
      patients with advanced disease, recently a new serum marker (OVX1) for the
      detection of early-stage endometrial cancer was reported. Serum OVX1 levels were
      measured using an OVX1 radioimmunoassay (RIA) or enzyme immunoassay (EIA) in 192
      patients with endometrial cancer. CA 125 levels were measured in 112 patients
      using the CIS ELSA CA 125 kit. Apparently healthy females had mean serum OVX1
      levels measured with the OVX1-EIA of 1.34 +/- 0.74 U/ml, while patients with
      endometriosis had mean OVX1 serum levels of 3.15 +/- 2.45 U/ml. The mean OVX1
      serum level for endometrial cancer patients was 2.00 +/- 1.32 U/ml. These values
      were 2.76 +/- 1.62, 6.10 +/- 4.66, and 5.37 +/- 3.49, respectively, using the
      OVX1-RIA assay. Applying a cutoff value of 2.8 U/ml, serum OVX1-EIA levels in
      endometrial cancer patients were increased in 25 of 127 patients (19.7%) with
      stage I disease, 5 of 17 patients with stage II (29.4%), 5 of 22 patients (22.7%)
      with stage III, and 4 of 11 patients (36.4%) with stage IV disease. Using the
      OVX1-RIA and a cutoff of 7.2 U/ml, serum levels were increased in 22 of 127
      (17.3%) stage I, 6 of 17 (35.3%) stage II, 5 of 22 (22.7%) stage III, and 6 of 11
      (54.5%) stage IV patients. Serum CA 125 levels, determined in a total of 112
      patients, were elevated above 35 U/ml in 12 of 79 patients (15.2%) with stage I,
      4 of 12 patients (33.3%) with stage II, 8 of 13 patients (61.5%) with stage III,
      and all of 8 patients (100%) with stage IV disease. While a good correlation
      between serum CA 125 levels and the clinical stage of the disease was found, no
      correlation could be detected for OVX1 and stage.

PMID- 9159341
TI  - Effects of electrochemotherapy on CaSki cells derived from a cervical squamous
      cell carcinoma.
AB  - Electrochemotherapy is a new approach to the treatment of tumors that takes
      advantage of the permeabilization of the cell membranes by electric pulses to
      facilitate the intracellular delivery of chemotherapeutic drugs into cells. Using
      the female genital squamous cell carcinoma cell line, CaSki, the antitumor
      effectiveness of electrochemotherapy was tested. In vitro studies showed that the
      cytotoxicity of some anticancer drugs, especially bleomycin, can be greatly
      enhanced by exposing cells to noncytotoxic electric pulses. This enhancement was
      significantly greater when the electric treatment was given after exposure to the
      drug than when applied preexposure. Treatment of nude mice bearing subcutaneous
      transplanted tumors with noneffective intraperitoneal doses of bleomycin followed
      by local delivery of electric pulses similar to those performed in vitro resulted
      in tumor reduction and complete disappearance after 12 days this
      electrochemotherapy. Histological changes in tumor tissue such as necrosis and
      degeneration were extensive even 6 hr after the electrochemotherapy. Thus the
      antitumor effects of bleomycin in mice can be considerably potentiated by local
      electric pulses, suggesting that electrochemotherapy with bleomycin may have
      promise for treatment of vulvar or ectocervical squamous cell carcinomas with
      early invasion.

PMID- 9159342
TI  - Serum levels of soluble intercellular adhesion molecule-1 (ICAM-1) and the
      expression of ICAM-1 mRNA in uterine cervical cancer.
AB  - The purpose of this investigation was to evaluate the serum level of soluble
      intercellular adhesion molecule-1 (sICAM-1) in patients with squamous cell
      carcinoma of the cervix. Serum levels of sICAM-1 were measured by enzyme-linked
      immunosorbent assay in patients with cervical cancer (stage 0 through IV).
      Expression of mRNA in tumor tissues was evaluated by reverse transcriptase
      polymerase chain reaction. Serum level of sICAM-1 in patients with advanced-stage
      (II-IV) or recurrent cervical cancer was found to be increased significantly.
      Expression of ICAM-1 mRNA was observed in most tumor tissues. Results suggest
      that sICAM-1 is shed from the cancerous tissue in patients with squamous cell
      carcinoma of the cervix.

PMID- 9159343
TI  - Prognostic value of preoperative squamous cell carcinoma antigen level in
      patients surgically treated for cervical carcinoma.
AB  - Preoperative evaluation of squamous cell carcinoma antigen (SCCa) was performed
      in 220 patients with surgically treated early-stage carcinoma of the cervix. The
      median duration of follow-up was 1.9 years. SCCa was significantly higher in
      tumors with a squamous element (P < 0.001). There was a squamous element in 171
      tumors. SCCa was elevated (>2 ng/ml) in 21.6%. Significantly higher levels were
      associated with stage II disease (P < 0.001), tumors >4-cm size (P < 0.001), and
      lymph node metastases (P < 0.001). The positive predictive value for lymph node
      metastases at >2, >4, and >8.6 ng/ml SCCa is 51.4, 70.0, and 100% and the
      sensitivity is 58.1, 45.2, and 22.6%, respectively. Low SCCa is a poor predictor
      of absence of lymph node metastasis. The median SCCa for patients who developed
      tumor recurrence was greater than those who remained disease free (1.7 and 1.0
      ng/ml, respectively, P = 0.009); however, in a multivariate analysis only lymph
      node metastasis and tumor size were of independent prognostic significance (P =
      0.002 and P = 0.004, respectively). SCCa level >8.6 ng/ml is highly predictive of
      lymph nodal disease. There is no independent prognostic significance in patients
      with early-stage surgically treated cervical carcinoma.

PMID- 9159344
TI  - Neoplasia associated with atypical glandular cells of undetermined significance
      on cervical cytology.
AB  - The clinical importance of atypical glandular cells of undetermined significance
      (AGUS) on cervicovaginal smear has not been well defined. Between January 1990
      and April 1996, 127 smears were reported as showing AGUS changes by the
      cytopathology division at the University of Massachusetts Medical Center. The
      medical records of these women were reviewed: 17 women were excluded because of
      previous hysterectomy or gynecologic cancer, 85 were biopsied, 16 were followed
      by repeat smears, and 9 were lost to follow-up. Forty-four women had negative
      biopsies or cervicitis. There were 15 endometrial lesions: 10 hyperplasias (2
      with atypia) and 5 adenocarcinomas. Twenty-five women had cervix lesions
      including 3 endocervical atypias, 12 low-grade cervical intraepithelial neoplasia
      (CIN), 6 high-grade CIN, one adenocarcinoma in situ, and 3 invasive
      adenocarcinomas. One patient had ovarian cancer. Two of the 16 women followed by
      repeat pap smear eventually had a cancer diagnosis: one with cervix cancer and
      one with colon cancer. We were unable to identify a subgroup of women with AGUS
      who were at increased risk for serious pathology when we compared multiple
      demographic variables, symptoms, or the presence of coexistent squamous
      abnormalities on cervical cytology. The mean age of the 15 women with endometrial
      lesions was 59.9 years, which was significantly older than those patients with
      cervix lesions who had a mean age of 38.9 years. The presence of AGUS on cervical
      cytology is a marker for significant gynecologic neoplasia and should be
      investigated with colposcopically directed biopsies, endocervical curettage, and,
      in older women, endometrial biopsy.

PMID- 9159345
TI  - p16INK4 and p15INK4B alterations in primary gynecologic malignancy.
AB  - Chromosome 9 abnormalities have been found in primary tumors and cell lines from
      human gynecologic malignancy. Alterations of p16INK4 and p15INK4B genes mapped on
      the band p21 of chromosome 9 have been detected in various human tumors, but the
      role of these genes as tumor suppressors in vivo appear to be dependent on tumor
      type. Polymerase chain reaction (PCR)-based analysis was performed to search for
      lesions of these genes in 202 primary gynecologic malignancies. Homozygous
      deletions of p16INK4 were detected in 7 of 128 (5%) cervical, 1 of 41 (2%)
      endometrial, 2 of 27 (7%) ovarian, and 3 of 6 (50%) vulvar carcinomas, while
      homozygous deletions of p15INK4B were detected in 19 of 128 (15%) cervical, 1 of
      41 (2%) endometrial, 9 of 27 (33%) ovarian, and 3 of 6 (50%) vulvar carcinomas,
      respectively. No mutations were found in exon 2 of p16INK4 from 161 cases of
      gynecologic malignancy without deletion of p16INK4. All 3 cases of vulvar
      carcinoma showing homozygous deletions of p16INK4 and p15INK4B were at advanced
      clinical stage (stage III-IV), while all 7 cases of cervical carcinoma and 2
      cases of ovarian carcinoma showing homozygous deletion of p16INK4 were at early
      stage (stage I-II). The results indicate that homozygous deletions of p16INK4
      and/or p15INK4B genes may play a role in a subset of primary gynecologic
      malignancy.

PMID- 9159346
TI  - Chemoprophylaxis with ciprofloxacin in ovarian cancer patients receiving
      paclitaxel: a randomized trial.
AB  - The objective of this study was to evaluate the efficacy of oral ciprofloxacin in
      preventing febrile morbidity superimposed on the neutropenia induced from a
      paclitaxel regimen in ovarian cancer patients. Eligible patients received
      paclitaxel at doses of 135 to 175 mg/m2 alone or in combination with a platinum
      agent. They were randomized to either an observation (control) group or a
      ciprofloxacin prophylaxis group. Patients in the ciprofloxacin group received 500
      mg ciprofloxacin orally twice a day once the absolute neutrophil count (ANC) was
      less than 500/mm3 and continued until the ANC was greater than 1000/mm3. Ninety
      patients were enrolled between the control (n = 45) and ciprofloxacin (n = 45)
      groups. They received 371 cycles of a paclitaxel-based regimen with 177 and 194
      cycles in the control and ciprofloxacin groups, respectively. Ciprofloxacin
      prophylaxis was prescribed for 138 (71%) of the cycles in the ciprofloxacin group
      and was given for a mean duration of 7.7 days per cycle. The groups were similar
      in disease status and risk factors for neutropenia. Fifteen patients in the
      control group developed febrile neutropenia versus 12 of those in the
      ciprofloxacin group (P = 0.69). The mean ANC and mean length of hospital stay for
      neutropenic fever were also similar between groups. There was a greater frequency
      of an ANC < 100 associated with those prophylaxed with ciprofloxacin (P = 0.01).
      Only 44% of the febrile episodes were associated with a positive culture.
      Staphylococcus aureus was the most frequently reported organism isolated.
      Considering these results, it does not appear that febrile neutropenia is reduced
      by ciprofloxacin during grade IV neutropenia.

PMID- 9159347
TI  - Analysis of Ki-ras, p53, and MDM2 genes in uterine leiomyomas and
      leiomyosarcomas.
AB  - Uterine sarcomas are unusual neoplasms of the female genital tract whose
      molecular etiology is largely unknown. We examined 20 leiomyomas as well as 23
      uterine leiomyosarcomas for the presence of mutations in the Ki-ras and p53
      genes, and overexpression of the MDM2 gene. Codons 12, 13, and 61 from the Ki-ras
      gene were characterized for the presence of mutations by restriction enzyme
      polymorphisms using mismatched primers and nucleic acid sequencing as
      appropriate. Activated Ki-ras genes were identified in 3/20 leiomyomas and 0/23
      leiomyosarcomas. The p53 gene was analyzed by SSCP, nucleic acid sequencing, and
      immunohistochemical staining. None of 20 leiomyomas and 6/23 leiomyosarcomas
      exhibited p53 abnormalities. The SSCP/sequencing results did not consistently
      correlate with the IHC staining. MDM2 overexpression occurred in 0/20 leiomyomas
      and 3/23 sarcomas. Clinical correlation suggested that tumors with p53 mutations
      have a higher histologic grade or stage at presentation. We conclude that
      leiomyomas and leiomyosarcomas have different patterns of molecular alterations
      and are separate biologic entities. In addition, p53 and MDM2 overexpression may
      play a role in the development of a subset of leiomyosarcomas.

PMID- 9159349
TI  - Identification of H, K, and N-ras point mutations in stage IB cervical carcinoma.
AB  - OBJECTIVE: The ras oncogenes, Harvey (H), Kirsten (K), and neuroblastoma (N), are
      a family of genes coding for a membrane-associated protein (p21) which possesses
      inherent guanine triphosphatase (GTPase) activity. Point mutagenesis at codons
      12, 13, and 61 has been implicated in ras activation and subsequent cellular
      transformation. Given the epidemiologic relationship of HPV infection with
      cervical carcinoma and the tumorigenic interaction of HPV and mutated ras
      oncogenes, this study was undertaken to identify if mutated ras oncogenes were
      present in early invasive cervical carcinomas. METHODS: A combination of
      polymerase chain reaction (PCR) and dot-blot hybridization was used to determine
      the frequency and types of ras point mutants occurring in cervical carcinoma.
      Thirty-three patients with early-stage cervical carcinoma were identified. DNA
      was extracted from archival tumor samples. ras genes were PCR amplified using
      flanking primers and hybridized with a series of labeled allele-specific
      oligonucleotides corresponding to wild-type forms of K12,61, N12,13,61, and
      H12,61, as well as to all combinations of substitution mutations (7 wild-type, 45
      mutants). RESULTS: ras mutations were identified in 24.2% of specimens. The
      detected mutations in H, K, and N-ras all occurred at codon 61. This was not the
      result of PCR or hybridization artifact in that mutations were detected in
      position 12 and 13 in appropriate control samples. CONCLUSIONS: Mutant ras has
      been shown to convert HPV immortalized keratinocytes to the tumorigenic state.
      Our results indicate that a significant percentage (24.2%) of these early-stage
      cervical cancers contain activated ras. Additional studies will be needed to
      evaluate whether codon 61 represents a characteristic "hot-spot" of ras mutation
      in a subset of cervical carcinoma.

PMID- 9159348
TI  - Carboplatin as a radiation sensitizer in locally advanced cervical cancer: a
      pilot study.
AB  - Radiation therapy is the mainstay in treatment of locally advanced cervical
      carcinoma. Several chemotherapeutic agents have been used as radiation
      sensitizers in the treatment of cervical cancer in an effort to improve local
      response and survival. A prospective study was designed to evaluate carboplatin
      as a radiosensitizer in advanced cervical cancer. Standard radiotherapy
      techniques were used to treat patients with Stage IIA-IIIB cervical cancer.
      Intravenous carboplatin was administered twice weekly concurrent with external
      beam radiation. Of 22 evaluable patients, there were 19 complete responders of
      whom 15 remain alive: 11 patients were alive and disease free at last visit for a
      median duration of 15 months follow-up (range, 4-43 months) and 4 patients remain
      alive with disease for a median duration of 17 months (range, 3-55 months). Seven
      have died, one of whom was without evidence of disease. There were no treatment
      related deaths and no grade 4 toxicity. The most significant adverse effect was
      hematologic resulting in four patients with grade 3 neutropenia or anemia. There
      were no fistulae or late gastrointestinal or genitourinary complications. This
      pilot study suggests that carboplatin administered with standard radiation is
      safe, well-tolerated, and thus may be useful as a radiation sensitizer in the
      treatment of locally advanced cervical cancer.

PMID- 9159351
TI  - Successful treatment of brain metastases from ovarian cancer using gamma-knife
      radiosurgery.
AB  - We describe a case with multiple brain metastases from ovarian cancer which were
      successfully treated by a multimodality approach including gamma-knife
      radiosurgery. This case was diagnosed as epithelial ovarian cancer, FIGO stage
      IV, with supraclavicular lymph node metastasis and malignant pleural effusion.
      She underwent cisplatin-based chemotherapy before and after cytoreductive surgery
      for 9 months and then achieved clinical complete remission for 27 months.
      Multiple brain metastases occurred 36 months after the initial diagnosis of
      ovarian cancer. She had no recurrent lesions outside the brain. She underwent
      surgical resection of the two accessible lesions and then gamma-knife
      radiosurgery for another unresectable lesion after 30 Gy cranial irradiation. The
      multimodal treatment including gamma-knife radiosurgery has produced complete
      remission of multiple brain metastases for 21 months with good quality of life.
      Accordingly, at the moment, i.e., 5 years after the initial diagnosis of the
      disease, she remains in a disease-free state.

PMID- 9159350
TI  - Neoadjuvant chemotherapy in stage IB2 squamous cell carcinoma of the cervix.
AB  - To determine the effects of neoadjuvant chemotherapy (NAC) in the management of
      cervical carcinoma Stage IB2 (tumor diameter > 4 cm), we reviewed 52 surgically
      treated patients diagnosed between January 1987 and December 1993. There were 20
      patients treated with preoperative neoadjuvant chemotherapy and 32 treated by
      primary radical hysterectomy. Mean tumor diameter was significantly larger in the
      neoadjuvant, compared with the primary surgery group (6.5 +/- 1.8 vs 5.4 +/- 0.7,
      P = 0.003). In the NAC group, 5 of 20 patients were treated with three courses of
      cisplatin, methotrexate, and bleomycin every 21 days, whereas 15 of 20 patients
      received three courses of cisplatin, vincristine, and bleomycin every 10 days.
      Postoperative adjuvant therapy consisting of either radiation or chemotherapy was
      employed in 13/20 patients (65%) in the NAC group and 20/32 patients (63%) in the
      primary surgical group. At a median follow-up of 52.5 months, 4/20 patients (20%)
      in the NAC group recurred vs 11/32 (34%) in the primary surgery group. The
      overall response rate to NAC was 90%, with 2/20 complete clinical responders and
      16/20 partial responders. High-risk pathologic factors were less commonly
      observed in the NAC group when compared with the primary surgical group with the
      incidence of nodal metastases, positive vascular space involvement, undiagnosed
      parametrial disease, and > or = 75% depth of invasion observed in 10.0% vs 37.5%,
      20.0% vs 46.9%, 0.0% vs 15.6%, and 30.0% vs 68.8%, respectively. No differences
      were noted in operative time or blood loss. Cox proportional-hazards analysis
      indicated that the most significant prognostic factor was depth of invasion.
      Although the patients who received neoadjuvant chemotherapy had significantly
      larger tumors at baseline, their 5-year survival rate was slightly higher than
      that of the primary surgery group (80.0% vs 68.7%, P = 0.162). Patients receiving
      neoadjuvant chemotherapy, despite having significantly larger pretreatment
      tumors, had fewer high-risk pathologic factors, postoperatively. Although this
      was a small, nonrandomized study, the relative improvement in pathologic response
      and long-term outcome associated with neoadjuvant chemotherapy was encouraging.
      This highlights the need for a prospective randomized clinical trial to establish
      whether neoadjuvant chemotherapy can significantly improve the long-term outcome
      of women with Stage IB2 squamous cell carcinoma of the cervix.

PMID- 9159352
TI  - Acute hyperglycemia following intraperitoneal irrigation with 10% dextrose in a
      patient with pseudomyxoma peritonei.
AB  - Pseudomyxoma peritonei is a condition characterized by the production of large
      amounts of mucopolysaccharide by a neoplastic epithelium. Although surgical
      debulking and removal of the mucinous ascites may be attempted, complete removal
      of the material is often impossible. Intraperitoneal lavage with 10% dextrose in
      water (D10W) has been advocated to prevent reaccumulation of the mucus and
      complications such as bowel obstruction requiring repeat laparotomy. We describe
      a patient undergoing operation for a large abdominopelvic mass. At laparotomy, a
      mucinous cystadenocarcinoma of the ovary was found with a great deal of
      tenacious, mucinous ascites and peritoneal implants. In an effort to more
      efficiently remove the mucus and prevent subsequent reaccumulation,
      intraperitoneal irrigation with 10% dextrose in water (D10W) was performed. The
      patient, who gave no history of prior glucose intolerance, was soon thereafter
      found to be profoundly hyperglycemic (serum glucose >500 mg/dl). She was treated
      with insulin and recovered without evident sequelae. Practitioners should be
      aware of this potentially dangerous complication associated with intraperitoneal
      dextrose instillation.

PMID- 9159353
TI  - A case of a patient diagnosed with malignant mixed Mullerian tumor of the ovary
      who conceived after conservative surgery and adjuvant chemotherapy.
AB  - A case of successful pregnancy after treatment of stage Ia malignant mixed
      Mullerian tumor of the ovary is described. This tumor is very rare and usually
      occurs in postmenopausal women. cis-platinum-based chemotherapy following the
      primary operation in the early stage is the most effective treatment, although
      most of the tumors have been found in the advanced stage. In this patient,
      treatment with unilateral salpingo-oophorectomy to preserve fertility was
      performed and followed by cis-platinum-based chemotherapy for 5 years. Two years
      after completion of the chemotherapy, she spontaneously conceived and the course
      of the pregnancy has been uneventful to this point.

PMID- 9159354
TI  - Complete remission of refractory gestational trophoblastic disease with brain
      metastases treated with multicycle ifosfamide, carboplatin, and etoposide (ICE)
      and stem cell rescue.
AB  - Patients with chemotherapy-refractory gestational trophoblastic disease and brain
      metastasis are considered to have a very poor prognosis. We present the case of a
      patient who had failed several chemotherapeutic regimens. Despite transient
      responses to chemotherapy, she had not achieved a complete remission in 3 years,
      and had developed systemic disease and recurrent brain metastasis. She was
      treated with four cycles of high-dose ifosfamide, carboplatin, and etoposide with
      blood progenitor cell support. She tolerated this regimen well and has obtained a
      complete remission that is ongoing for 12 months.

PMID- 9159355
TI  - Pelvic hematoma following angiography: another cause of elevated serum CA-125.
AB  - The presence of a pelvic mass in a patient with an elevated serum CA-125 suggests
      the possibility of a gynecologic malignancy. However, an increasing number of
      nonneoplastic causes of elevated serum CA-125 have been reported. This is the
      first report of a pelvic hematoma associated with elevated serum CA-125. Two
      weeks following cardiac catheterization at time of myocardial infarction a
      patient was noted to have a complex pelvic mass on ultrasound and serum CA-125 of
      53 units per milliliter. Abdominal-pelvic CT-scan showed a small left pleural
      effusion, minimal ascites, left lower quadrant abdominal wall masses consistent
      with omental metastases, and a 9.4 x 10.3 x 9.0-cm complex left adnexal mass. At
      exploratory laparotomy a large organized hematoma in the left paravesical space
      was adherent to both the left external iliac artery and the left bladder wall.
      This mass could have been managed expectantly with percutaneous aspiration if a
      nonmalignant diagnosis had been more strongly considered.

PMID- 9159356
TI  - Cornelius G. Dyke and the Neurological Institute of New York: the foundations of
      American neuroradiology.

PMID- 9159357
TI  - The developing anterior skull base: CT appearance from birth to 2 years of age.
AB  - PURPOSE: To describe the normal CT appearance of the developing anterior skull
      base in children 24 months of age and younger. METHODS: A retrospective review of
      the CT examinations of a healthy population of 61 subjects newborn through 24
      months of age was performed. Two investigators independently reviewed the
      examinations, making measurements and observations regarding the length of the
      skull base, ossification pattern, and development of the crista galli,
      perpendicular plate of the ethmoid bone, and fovea ethmoidalis. RESULTS: At
      birth, the anterior skull base is largely cartilaginous. Ossification begins in
      the roof of the ethmoidal labyrinth laterally and spreads toward the midline. By
      6 months of age, 50% of the anterior skull base has completely ossified. This
      percentage steadily increases over the first 2 years of life, and by 24 months,
      84% of the anterior skull base is completely ossified, with a cartilaginous gap
      anteriorly in the region of the foramen cecum, the residual unossified portion.
      Ossification of the crista galli and perpendicular plate of the ethmoid bone
      begins around 2 months of age, shows a steady increase in ossification to 14
      months of age, then increases little to 24 months of age. The fovea ethmoidalis
      begins development by 6 months of age, with the anterior portion the most
      developed in 82% of the population. CONCLUSION: The timing and pattern of
      ossification we observed differ somewhat from that reported in prior radiologic
      and anatomic studies, with the earliest bony bridging of the ethmoidal complex to
      the crista galli seen as early as 2 months of age. Development of the anterior
      skull base follows a predictable and orderly pattern that is important for
      understanding how to avoid errors in interpreting CT examinations through this
      region.

PMID- 9159358
TI  - Age-related changes in the pediatric brain: quantitative MR evidence of
      maturational changes during adolescence.
AB  - PURPOSE: To determine whether a quantitative MR imaging method to map spin
      lattice relaxation time (T1) can be used to characterize maturational changes in
      the normal human brain. METHODS: An inversion-recovery technique was used to map
      T1 transversely at the level of the basal ganglia in a study population of 19
      healthy children (4 to 10 years old) and 31 healthy adolescents (10 to 20 years
      old), and in a normative population of 20 healthy adults (20 to 30 years old).
      RESULTS: Nonparametric analysis of variance showed that T1 decreases with age in
      the genu, frontal white matter, caudate, putamen, anterior thalamus, pulvinar
      nucleus, optic radiation, cortical gray matter (all P < .0001), and occipital
      white matter. There was a significant reduction in T1 between childhood (mean
      age, 7.1 +/- 1.4) and adolescence (mean age, 13.5 +/- 2.6) in all brain
      structures, but there was also a significant reduction in T1 between adolescence
      (mean age, 13.5 +/- 2.6) and adulthood (mean age, 26.5 +/- 3.4) in all brain
      structures except occipital white matter. Regression shows that T1 declines to
      within the range (mean +/- 2 SD) of young adult T1 values by about 2 years in the
      occipital white matter, by about 4 years in the genu, by 11 years in the cortical
      gray matter, by 11 years in the frontal white matter, and by 13 years in the
      thalamus. CONCLUSION: Brain structures mature at strikingly different rates, yet
      the ratio of gray matter T1 to white matter T1 does not change significantly with
      age. Thus, conventional MR imaging methods based on inherent contrast are
      insensitive to these changes. Age-related changes tend to reach completion sooner
      in white matter than in gray matter tracts. Such normative data are essential for
      studies of specific pediatric disorders and may be useful for assessing brain
      maturation in cases of developmental delay.

PMID- 9159359
TI  - Detection of subtle changes in the brains of infants and children via subvoxel
      registration and subtraction of serial MR images.
AB  - PURPOSE: To compare conventional two-dimensional multisection images with
      registered three-dimensional volume and subtraction images for detecting subtle
      changes in the brains of infants and children. METHODS: Twenty-six patients (24
      with hemorrhagic/ischemic lesions) and one each with perinatal infection and
      Sturge-Weber disease were examined on two or more occasions with conventional
      multisection T1- and T2-weighted sequences as well as with 3-D T1-weighted volume
      sequences. A registration program was used to match the volume images to subvoxel
      dimensions, and subtracted images (second volume set minus the first) were
      obtained. The multisection images were compared with the 3-D and subtracted
      images and graded for detection of changes in a variety of brain structures.
      RESULTS: In 16% to 33% of comparisons of different structures, the multisection
      images and the 3-D registered and subtracted images showed changes equally well.
      The 3-D registered and subtracted images were better than the multisection images
      in 67% to 84% of comparisons for detection of changes in the cerebral
      hemispheres, ventricles, brain stem, cerebellum, and in lesions. Statistically
      significant differences were found between the graded performance of the
      registered 3-D images and the conventional 2-D images in detecting cerebral
      infarction and hypoxic ischemic encephalopathy. In the late phase following
      neonatal cerebral infarction (1 to 11 months), the 3-D registered and subtracted
      images revealed growth of the brain at the margins of the lesions. CONCLUSION:
      Subvoxel registration of serial MR images may be of value in detecting subtle
      changes in the brains of infants and children.

PMID- 9159360
TI  - Angiographic changes after pial synangiosis in childhood moyamoya disease.
AB  - PURPOSE: To describe the angiographic changes accompanying the surgical treatment
      of moyamoya disease by pial synangiosis and to compare these changes with patient
      outcome. METHODS: The preoperative and postoperative cerebral angiograms, MR
      images, and clinical records of 13 children treated with pial synangiosis for
      moyamoya disease were reviewed. RESULTS: After synangiosis, 10 patients had
      significant neurologic improvement and three had minimal or no improvement.
      Postoperative MR images showed no new infarctions. Well-developed (grade A or B)
      transpial or transdural collaterals to the brain were present at the site of
      synangiosis in 84% of the surgically treated hemispheres. Cerebrovascular
      occlusive changes increased postoperatively in 76% of hemispheres. After
      synangiosis, moyamoya collaterals were increased in 48%, unchanged in 16%, and
      decreased in 36% of surgically treated hemispheres. All 10 patients with grade A
      or B collaterals bilaterally after synangiosis were asymptomatic or improved on
      follow-up. CONCLUSION: Pial synangiosis typically results in an increase in
      collaterals from the superficial temporal artery or middle meningeal artery to
      the brain. Synangiosis appears to result in stabilization or improvement in
      neurologic symptoms but does not prevent the angiographic progression of disease
      or the development of moyamoya collaterals. The angiographic demonstration of
      well-formed collaterals after synangiosis is associated with a favorable clinical
      outcome.

PMID- 9159361
TI  - Sialoblastoma (embryoma): MR findings of a rare pediatric salivary gland tumor.
AB  - We report the findings in a 21-month-old girl who had a noninfiltrating mass in
      the left cheek, just anterior to the masseter muscle, which, at surgery, proved
      to be a sialoblastoma. Sialoblastoma has a histologic appearance reminiscent of a
      primitive state of salivary gland development; that is, it shows an arrested
      state of salivary maturation. MR imaging in this case showed that the lesion was
      isointense with muscle on T1-weighted images, had a high-intermediate signal
      intensity similar to that of fat on T2-weighted images, and enhanced sparsely and
      nonhomogeneously.

PMID- 9159362
TI  - Epilepsy for the neuroradiologist.

PMID- 9159363
TI  - Increased activity of the ipsilateral motor cortex during a hand motor task in
      patients with brain tumor and paresis.
AB  - PURPOSE: To look for changes in the motor cortex in patients with brain tumors.
      METHODS: Both cerebral hemispheres in seven patients with brain tumors were
      examined with functional MR imaging during a motor task performed by the hand
      opposite the site of tumor. The ratio of the activated area in the motor cortex
      ipsilateral/contralateral to the tested hand was calculated for each subject.
      Twenty healthy subjects were also examined in the same manner for comparison.
      RESULTS: The ratio of the ipsilateral/contralateral activated area was abnormally
      high in three patients with tumor-related paresis of the tested hand. The ratio
      was significantly greater in patients with paresis than in healthy subjects.
      CONCLUSION: This study demonstrated increased activity in the ipsilateral
      (unaffected) motor area during a hand motor task in patients with brain tumor and
      paresis, which was thought to reflect compensatory reorganization induced by the
      functional damage.

PMID- 9159364
TI  - Mapping of the sensorimotor cortex: functional MR and magnetic source imaging.
AB  - PURPOSE: To assess the reliability and comparability of functional MR imaging and
      magnetic source imaging for mapping the somatosensory cortex. METHODS: Parallel
      studies were performed in eight volunteer subjects in whom both hemispheres were
      measured with the use of painless tactile stimulation of the tip of each index
      finger. Magnetic source imaging was performed using a 37-channel biomagnetometer;
      evoked magnetic fields were analyzed using the single-equivalent dipole
      representation to ascertain the neuronal source. Functional MR imaging was
      performed on a 1.5-T MR unit. Blocks of images during periods of rest and
      activation were acquired using gradient-echo echo-planar imaging. Correlation
      analysis identified pixels in which signal intensity correlated with the stimulus
      function. A subsequent requirement for spatial connectivity of activation was
      imposed to reduce the random occurrence of pixels satisfying the correlation
      criteria. RESULTS: Using temporal and spatial statistical criteria for
      activation, we found that functional MR imaging showed activation in 1 of 16
      hemispheres. In three cases, this was accompanied by activity either frontally or
      ipsilateral to the stimulus. Magnetic source imaging showed parietal
      contralateral location in all 16 cases. Where successful localization was
      achieved with both methods, the separation between sources appeared to be between
      1 and 4 cm. Functional MR imaging localizations tended to lie more superficially
      than the magnetic source imaging localizations. Performance of a simple motor
      task, rather than use of somatosensory stimulation, resulted in a cortical signal
      change detectable with a similar functional MR imaging approach in all cases,
      suggesting the more robust nature of this stimulus. CONCLUSIONS: Functional
      mapping of the somatosensory cortex can be achieved with functional MR imaging or
      magnetic source imaging. Functional MR imaging yields more spurious locations and
      fails to show localization more often. If neuronal signal propagation pathways
      are of interest, the temporal resolution of functional MR imaging alone may be
      inadequate. A combination of magnetic source imaging and functional MR imaging
      may allow improved sensitivity, fewer false-positive results, and high spatial
      and temporal resolution.

PMID- 9159365
TI  - The endolymphatic duct and sac.

PMID- 9159366
TI  - Intracranial chondroma.

PMID- 9159367
TI  - Magnetization transfer study of HIV encephalitis and progressive multifocal
      leukoencephalopathy. Groupe d'Epidemiologie Clinique du SIDA en Aquitaine.
AB  - PURPOSE: To ascertain whether the use of magnetization transfer (MT) in MR
      imaging can characterize tissue destruction in human immunodeficiency virus (HIV)
      positive patients with presumed progressive multifocal leukoencephalopathy (PML)
      or HIV encephalitis. METHODS: Brain MR studies that included MT were obtained in
      three groups: 11 healthy control subjects, 10 HIV-positive patients with clinical
      and radiologic findings of PML, and 13 HIV-positive patients with HIV
      encephalitis. MT ratios (MTRs) were calculated in PML and HIV encephalitis
      lesions and in normal-appearing white matter in the patients and control
      subjects. RESULTS: PML lesions revealed a dramatic decrease in MTR (22% +/- 2.3).
      HIV encephalitis lesions had statistically significantly higher MTR values (40%
      +/- 3.8) than PML lesions. The MTR of normal-appearing white matter was
      significantly higher in the control subjects (47% +/- 2.3) than in the PML group
      (46% +/- 3.3) or the HIV encephalitis group (44% +/- 2.6). CONCLUSION: MTR
      determinations suggest the possibility of distinguishing PML from HIV
      encephalitis and of indicating whether HIV encephalitis is involved in white
      matter that appears normal on conventional MR images.

PMID- 9159368
TI  - Granulomatous amebic encephalitis caused by leptomyxid amebae in an HIV-infected
      patient.
AB  - MR images of granulomatous amebic encephalitis caused by leptomyxid amebae in an
      HIV-infected patient showed both heterogeneous and ring-enhancing hemorrhagic
      lesions. The brain was diffusely involved, including the brain stem, deep gray
      matter nuclei, and corticomedullary junction regions of all lobes.

PMID- 9159369
TI  - Fast fluid-attenuated inversion-recovery MR of intracranial infections.
AB  - PURPOSE: To assess the usefulness of fast fluid-attenuated inversion-recovery
      (FLAIR) MR sequences in the diagnosis of intracranial infectious diseases.
      METHODS: We compared fast FLAIR images with conventional spin-echo images (T1-
      and T2-weighted) obtained in 20 patients with infectious diseases (six with
      encephalitis, five with brain abscesses, three with meningitis, two with
      meningoencephalitis, two with Creutzfeldt-Jakob disease, one with epidural
      empyema, and one with cysticercosis). Two neuroradiologists independently
      reviewed the FLAIR images and compared them with the conventional spin-echo
      images, obtaining agreement in all patients. RESULTS: FLAIR images of diagnostic
      quality were obtained in 18 patients. In two patients, FLAIR images were degraded
      by motion. Lesions in the patients with encephalitis and meningoencephalitis were
      better delineated on FLAIR images than on spin-echo images. FLAIR images clearly
      depicted lesions in the basal ganglia in both patients with Creutzfeldt-Jakob
      disease. In patients with brain abscess, meningitis, cysticercosis, and epidural
      empyema, FLAIR images provided no more information than conventional spin-echo
      images, and the lesions were seen better on postcontrast T1-weighted spin-echo
      images. CONCLUSION: Fast FLAIR images showed pathologic changes in intracranial
      infectious diseases better than or as well as conventional T2- and proton density
      weighted spin-echo sequences. However, postcontrast T1-weighted spin-echo
      sequences resulted in better visibility of abscess, meningitis, cysticercosis,
      and epidural empyema than did FLAIR images.

PMID- 9159370
TI  - Intraarterial thrombolysis in a pig model: a preliminary note.
AB  - PURPOSE: To develop a pig model of arterial thrombosis suitable for assessing
      different methods of thrombolysis and to use this model to compare the efficacy
      of intraarterial thrombolysis performed by continuous proximal urokinase infusion
      versus mechanical clot disruption combined with intrathrombic urokinase
      injection. METHODS: In a control group of five pigs, a thrombus was made in a
      short segment of femoral artery and observed for 2 hours to assess its stability.
      In a treatment group of six pigs, intraarterial thrombolysis was performed
      immediately after thrombus formation. Thrombolysis was accomplished by
      continuously infusing urokinase into the proximal leading edge of the thrombus in
      three pigs and by mechanical clot disruption combined with intrathrombic
      urokinase injection in the remaining three pigs. RESULTS: There was no
      spontaneous reestablishment of flow in the control group during the 2-hour
      observation period. In the first treatment group, no flow was observed after a 1
      hour treatment period when urokinase was infused continuously into the proximal
      edge of the thrombus. In the second treatment group, with mechanical clot
      disruption and intrathrombic urokinase injection, some degree of flow was
      observed in all three pigs. Reestablishment of flow was more sustained and of a
      greater degree with the addition of systemic heparinization. CONCLUSION: This
      animal model could provide a useful way to evaluate and compare different methods
      of thrombolysis. Our results suggest that mechanical clot disruption combined
      with intrathrombic urokinase injection is more effective in achieving
      reestablishment of flow than is continuous infusion of urokinase into the
      proximal edge of the thrombus.

PMID- 9159371
TI  - Embolization of dural cavernous fistulas via superior ophthalmic vein approach.
AB  - PURPOSE: To present the results of our treatment of dural cavernous sinus
      fistulas with surgical exposure of the superior ophthalmic vein (SOV), retrograde
      venous catheterization, and coil embolization of the cavernous sinus. METHODS:
      Twelve patients with dural cavernous sinus fistulas were treated via a retrograde
      transvenous SOV approach in our hospital during a 3-year period. All patients had
      been referred by ophthalmologists because of secondary glaucoma and decreased
      visual acuity. Angiography showed preferential venous drainage of the dural
      cavernous sinus fistulas to an enlarged ipsilateral SOV. A total of 13 SOV
      exposures were performed, one patient with bilateral fistulas required bilateral
      treatment. The vein was surgically exposed by an ophthalmologist and then
      catheterized. Platinum coils were delivered through a microcatheter at the
      fistula site and into the root of the SOV, until there was complete angiographic
      closure. RESULTS: Catheterization and embolization were successful in 12 of the
      13 patients, with complete angiographic occlusion of the fistula. Two patients
      with bilateral fistulas had transient worsening of symptoms on the contralateral
      side. Three patients required follow-up angiography. No early complications
      occurred, and late complications were minor in two cases. All patients except one
      with long-standing symptoms recovered premorbid visual acuity. At follow-up, 11
      (92%) of the 12 embolized fistulas remained occluded. CONCLUSIONS: Retrograde
      catheterization of the SOV and embolization of the cavernous sinus with coils is
      a direct, safe, and efficient way to occlude dural cavernous sinus fistulas.

PMID- 9159372
TI  - Arteriovenous malformation nidus catheterization with hydrophilic wire and flow
      directed catheter.
AB  - Arteriovenous malformation nidus catheterization with a flow-directed catheter at
      times can be difficult owing to tortuosity of the intracranial vasculature and
      distal location of the nidus. Since January 1995, hydrophilic wire has been used
      in conjunction with the 1.8F flow-directed microcatheter in over 150 vessel
      embolizations with cyanoacrylate glue for brain and spinal arteriovenous
      malformations at our institution. This technique has improved our success rate in
      achieving superselective catheterization of the nidus and has shortened the
      overall procedure time. To date, only one complication has occurred that was
      directly related to wire manipulation.

PMID- 9159373
TI  - Isolated dissecting aneurysm of the left posterior inferior cerebellar artery:
      endovascular treatment with a Guglielmi detachable coil.
AB  - An isolated progressive dissecting aneurysm of the left posterior inferior
      cerebellar artery (PICA) associated with a persistent trigeminal artery was
      successfully treated by endovascular occlusion of the proximal PICA with a
      Guglielmi detachable coil.

PMID- 9159374
TI  - Aneurysm clips made of titanium: magnetic characteristics and artifacts in MR.
AB  - PURPOSE: To evaluate the magnetic characteristics, artifact formation, and
      implant safety of titanium aneurysm clips for use in MR imaging. METHODS:
      Aneurysm clips made of titanium alloy TiAl6V4 were tested in a magnetometer to
      determine their magnetic susceptibility and in a 1.5-T MR imager using both a
      geometric phantom and an animal model. A commercially available alpha-Phynox clip
      served as the reference standard. RESULTS: We found minimal magnetization and a
      significant reduction in image artifacts with the titanium clip as compared with
      the Phynox clip. CONCLUSION: The titanium clips improve image quality,
      biocompatibility, and patient safety in medical MR applications.

PMID- 9159375
TI  - MR detection of secondary changes remote from ischemia: preliminary observations
      after occlusion of the middle cerebral artery in rats.
AB  - PURPOSE: To determine whether secondary MR changes occur in the thalamus or the
      substantia nigra after middle cerebral artery (MCA) occlusion in rats. METHODS:
      Sprague-Dawley rats were subjected to MCA occlusion. At varying intervals, proton
      density-, T1-, and T2-weighted images were obtained with a 4.7-T superconductive
      MR unit. RESULTS: T2-weighted images revealed an area of high signal intensity in
      the ipsilateral substantia nigra 4 days after occlusion. A lesion of low signal
      intensity appeared in the ipsilateral thalamus 7 days after surgery on proton
      density- and/or T2-weighted images. CONCLUSION: MR showed secondary changes in
      the thalamus and the substantia nigra after MCA occlusion in rats. MR imaging
      should provide more information on the neuropathology of the delayed neuronal
      degeneration after cerebral ischemia.

PMID- 9159376
TI  - Premature fat deposition in the salivary glands associated with Sjogren syndrome:
      MR and CT evidence.
AB  - PURPOSE: To investigate abnormal fat deposition in the major salivary glands
      associated with Sjogren syndrome. METHODS: We analyzed the fat deposition in the
      parotid and submandibular glands of 33 patients with Sjogren syndrome by using
      short-inversion-time inversion recovery (STIR) and fat-saturation MR sequences
      and CT values. RESULTS: All three in vivo techniques substantially confirmed
      premature deposition of fat in the major salivary glands in association with
      Sjogren syndrome. Furthermore, this change was characteristic of Sjogren
      syndrome, and the severity of fat deposition correlated well with the impaired
      rates of salivary flow in these patients. CONCLUSION: Monitoring of fat
      deposition might be useful for diagnosing Sjogren syndrome and assessing its
      progress in patients whose clinical and serologic findings are suggestive of the
      disease.

PMID- 9159377
TI  - Comparison of MR pulse sequences in the detection of multiple sclerosis lesions.
AB  - PURPOSE: To compare the sensitivity of conventional spin-echo, fast spin-echo,
      fast fluid-attenuated inversion recovery (FLAIR), and turbo gradient spin-echo MR
      sequences in the detection of multiple sclerosis lesions. METHODS: Conventional
      spin-echo, fast spin-echo, fast FLAIR, and turbo gradient spin-echo sequences
      were performed on a 1.0-T MR imager in seven patients with clinically definite
      multiple sclerosis. The images in each sequence were evaluated by two raters and
      consensus was reached by agreement. RESULTS: In comparing conventional spin-echo
      with fast spin-echo sequences, five lesions were seen only by conventional spin
      echo and 63 were seen only by fast spin-echo; in comparing conventional spin-echo
      with fast FLAIR sequences, 18 lesions were seen only by conventional spin-echo
      and 109 only by fast FLAIR; in comparing conventional spin-echo with turbo
      gradient spin-echo sequences, 51 lesions were seen only by conventional spin-echo
      and seven only by turbo gradient spin-echo; in comparing fast spin-echo with fast
      FLAIR sequences, 45 lesions were seen only by fast spin-echo and 52 only by fast
      FLAIR. CONCLUSION: Fast spin-echo and fast FLAIR sequences improve the
      sensitivity of MR imaging in the detection of multiple sclerosis lesions with
      reduced acquisition time as compared with conventional spin-echo sequences. These
      sequences should therefore be considered for serial studies in patients with
      multiple sclerosis. The sensitivity of turbo gradient spin-echo was inferior to
      the other sequences, but its reduced acquisition time could make this technique
      the ideal choice for patients who cannot tolerate longer examination times.

PMID- 9159378
TI  - Dynamic and conventional spin-echo MR of pituitary microlesions.
AB  - PURPOSE: To determine whether dynamic traditional spin-echo MR imaging, with the
      use of routine T1 parameters during contrast infusion, is superior to standard MR
      imaging after contrast administration for detecting microlesions of the pituitary
      gland. METHODS: Sixty-four patients with pituitary microlesions 3 to 10 mm in
      diameter were examined with a dynamic traditional spin-echo technique; that is, a
      typical T1 spin-echo sequence of 500-600/20-25/2 (repetition time/echo
      time/excitations), 3-mm-thick sections, 16-cm field of view, 256 x 128 matrix,
      and a scan time ranging from 2 minutes to 2 minutes 40 seconds during contrast
      infusion. In addition, standard imaging with unenhanced and contrast-enhanced
      spin-echo sequences were obtained. The three sequences were evaluated
      retrospectively and graded for gland-lesion contrast conspicuity, lesion
      homogeneity, and delineation of lesion margin. RESULTS: The dynamic sequence was
      judged to be better than the standard enhanced sequence for depicting
      microlesions in 42% to 47% of patients. Lesions were identified only on the
      dynamic study in an additional 1% to 14% of patients. Lesions were seen equally
      well on the standard and dynamic sequences only in 16% to 23% of cases. The
      standard postcontrast sequence was judged better in 12.5% to 17% of cases, with
      lesions identified only on the standard sequence in an additional 8% to 9%.
      CONCLUSION: Dynamic traditional spin-echo MR imaging improved lesion detection
      and provided increased clarity over standard sequences after contrast infusion.
      Both sequences are important, since lesions were detected only on the dynamic
      sequence in 11% to 14% of patients and only on the standard sequence in 8% to 9%
      of patients.

PMID- 9159379
TI  - Multiple cerebral aneurysms in identical twins.
AB  - We report the finding of multiple cerebral aneurysms in a pair of identical
      twins. One twin had subarachnoid hemorrhage and intracerebral hematoma; her
      sister had subarachnoid hemorrhage and intraventricular bleeding. Angiography in
      both cases showed multiple cerebral aneurysms. It is appropriate to recommend a
      cerebral angiographic examination of an asymptomatic twin after the other twin
      has suffered an aneurysmal subarachnoid hemorrhage.

PMID- 9159380
TI  - Myelolipoma of the thoracic spine.
AB  - We describe a myelolipoma of the thoracic spine in a patient with gradual and
      progressive myelopathy. MR imaging showed this predominately fatty lesion to be
      extradural in location.

PMID- 9159381
TI  - Globe tenting as a result of head trauma.
AB  - Ocular tenting in the setting of acute trauma, inflammatory processes, or carotid
      cavernous fistulas is reported to be associated with a poor outcome with respect
      to visual acuity. Therefore, acute decompressive intervention is recommended for
      these patients. We report a case of acute posttraumatic ocular tenting with acute
      visual compromise that resolved over 4 days with conservative management and
      intravenous corticosteroid therapy.

PMID- 9159382
TI  - Vanishing tumor of the temporalis muscle: repeated hemorrhage in an intramuscular
      venous hemangioma.
AB  - We present a rare case of venous hemangioma in the temporalis muscle that
      repeatedly and spontaneously enlarged and disappeared over several months. MR
      imaging depicted multiple fluid-fluid levels in the tumor alongside
      characteristic findings of hemangioma, indicating that the peculiar course was
      due to hemorrhage and blood resorption within the tumor.

PMID- 9159383
TI  - Atypical skull base paragangliomas.
AB  - We present two cases of unusually large skull base paragangliomas. The first
      tumor was accompanied by marked bony destruction of the central skull base and
      multiple associated cysts. The second tumor arose along the petrous ridge, with a
      large intracranial component. The CT, MR imaging, angiographic, histologic, and
      electron microscopic findings of these unusual lesions are described.

PMID- 9159384
TI  - Gene identification in autosomal dominant disorders.

PMID- 9159385
TI  - Cerebral MR and craniofacial syndromes.

PMID- 9159386
TI  - Ocular enhancement in Sturge-Weber syndrome.

PMID- 9159387
TI  - Prevalence of arachnoid granulations as detected with CT venography of the dural
      sinuses.

PMID- 9159388
TI  - MR findings of neonatal hypoglycemia.

PMID- 9159389
TI  - Annotated bibliography.

PMID- 9159390
TI  - Cell-cell interactions during plant development.

PMID- 9159391
TI  - DnaJ/hsp40 chaperone domain of SV40 large T antigen promotes efficient viral DNA
      replication.
AB  - The amino-terminal domain of SV40 large tumor antigen (TAg) is required for
      efficient viral DNA replication. However, the biochemical activity associated
      with this domain has remained obscure. We show here that the amino-terminal
      domain of TAg shares functional homology with the J-domain of DnaJ/hsp40
      molecular chaperones. DnaJ proteins function as cofactors by regulating the
      activity of a member of the 70-kD heat shock protein family. Genetic analyses
      demonstrated that amino-terminal sequences of TAg comprise a novel J-domain that
      mediates a specific interaction with the constitutively expressed hsc70 and show
      that the J-domain is also required for efficient viral DNA replication in vivo.
      Furthermore, we demonstrated that the J-domain of two human DnaJ homologs, HSJ1
      or DNAJ2, could substitute functionally for the amino-terminus of TAg in
      promoting viral DNA replication. Together, our findings suggest that TAg uses its
      J-domain to support SV40 DNA replication in a manner that is strikingly similar
      to the use of Escherichia coli DnaJ by bacteriophage lambda in DNA replication.
      However, TAg has evolved a more efficient strategy of DNA replication through an
      intrinsic J-domain to associate directly with a partner chaperone protein. Our
      observations provide evidence of a role for chaperone proteins in the process of
      eukaryotic DNA replication.

PMID- 9159392
TI  - Yeast Rad55 and Rad57 proteins form a heterodimer that functions with replication
      protein A to promote DNA strand exchange by Rad51 recombinase.
AB  - Saccharomyces cerevisiae RAD51, RAD55, and RAD57 genes, required for genetic
      recombination and DNA double-strand-break repair, encode proteins homologous to
      one another and to the Escherichia coli RecA protein. Rad51 protein catalyzes the
      DNA strand-exchange reaction with a dependence on ATP and on the heterotrimeric
      single-strand DNA (ssDNA) binding factor replication protein A (RPA). By several
      independent criteria, RAD55- and RAD57-encoded products are shown here to exist
      as a stable heterodimer, with a dissociation constant of <2 x 10(-10) M. In
      strand exchange, the reaction proceeds efficiently if RPA is incorporated after
      nucleation of Rad51 onto ssDNA, but if RPA is present during the nucleation
      phase, as is likely the case in vivo, the amount of strand-exchange products
      becomes relatively insignificant. Inclusion of the Rad55-Rad57 heterodimer with
      Rad51 and RPA results in a marked stimulation of strand exchange, providing
      evidence for a role of the Rad55-Rad57 heterodimer in overcoming the inhibitory
      effect of RPA.

PMID- 9159393
TI  - Direct regulation of rhodopsin 1 by Pax-6/eyeless in Drosophila: evidence for a
      conserved function in photoreceptors.
AB  - Pax-6 is a transcription factor containing both a homeodomain (HD) and a Paired
      domain (PD). It functions as an essential regulator of eye development in both
      Drosophila and vertebrates, suggesting an evolutionarily conserved origin for
      different types of metazoan eyes. Classical morphological and phylogenetic
      studies, however, have concluded that metazoan eyes have evolved many times
      independently. These apparently contradictory findings may be reconciled if the
      evolutionarily ancient role of Pax-6 was to regulate structural genes (e.g.,
      rhodopsin) in primitive photoreceptors, and only later did it expand its function
      to regulate the morphogenesis of divergent and complex eye structures. In support
      of this, we present evidence that eyeless (ey), which encodes the Drosophila
      homolog of Pax-6, directly regulates rhodopsin 1 (rh1) expression in the
      photoreceptor cells. We detect ey expression in both larval and adult terminally
      differentiated photoreceptor cells. We show that the HD of Ey binds to a
      palindromic HD binding site P3/RCS1 in the rh1 promoter, which is essential for
      rh1 expression. We further demonstrate that, in vivo, P3/RCS1 can be replaced by
      binding sites specific for the PD of Ey. P3/RCS1 is conserved in the promoters of
      all Drosophila rhodopsin genes as well as in many opsin genes in vertebrates.
      Mutimerized P3 sites in front of a basal promoter are able to drive the
      expression of a reporter gene in all photoreceptors. These results suggest that
      Pax-6/Ey directly regulates rhodopsin 1 gene expression by binding to the
      conserved P3/RCS1 element in the promoter.

PMID- 9159394
TI  - 14-3-3 epsilon positively regulates Ras-mediated signaling in Drosophila.
AB  - We have isolated mutations in the gene encoding a Drosophila 14-3-3 epsilon
      protein as suppressors of the rough eye phenotype caused by the ectopic
      expression of RAS1(V12). Using a simple loss-of-function 14-3-3 epsilon mutation,
      we show that 14-3-3 epsilon acts to increase the efficiency of RAS1 signaling.
      The 14-3-3 epsilon protein appears to function in multiple RTK pathways,
      suggesting that it is a general component of RAS1 signaling cascade. Sequence
      analysis of three dominant-negative alleles defines two regions of 14-3-3 epsilon
      that participate in RAS1 signaling. We also present evidence that 14-3-3 epsilon
      and 14-3-3 zeta, two 14-3-3 protein family members, are partially redundant for
      RAS1 signaling in photoreceptor formation and in animal viability. Our genetic
      data suggest that 14-3-3 epsilon functions downstream of or parallel to RAF, but
      upstream of nuclear factors in RAS1 signaling.

PMID- 9159395
TI  - Requirement for Drosophila 14-3-3 zeta in Raf-dependent photoreceptor
      development.
AB  - Based on biochemical and functional data obtained with tissue culture cells and
      yeast, 14-3-3 proteins have been implicated in a number of different signal
      transduction processes, in particular in the signal-dependent activation of
      protein kinases. We performed a functional analysis of 14-3-3 in a multicellular
      organism, initiated by the cloning of a 14-3-3 zeta homolog of Drosophila
      melanogaster, termed D14-3-3 zeta. D14-3-3 zeta transcripts are strongly enriched
      in the developing central nervous system. In addition, they are predominantly
      expressed in the region posterior to the morphogenetic furrow of the eye imaginal
      disc where cells differentiate as photoreceptors. In these cells D14-3-3 zeta is
      localized apically. Both the expression pattern and the subcellular localization
      are consistent with the proposed function of 14-3-3 proteins in Ras/Raf/MAPK
      signaling. D14-3-3 zeta mutant analysis combined with rescue experiments
      involving gain-of-function alleles of Raf and Ras indicate that D14-3-3 zeta is
      an essential component of the Raf/Ras signaling pathway and necessary for
      photoreceptor differentiation. It acts upstream of Raf and downstream of Ras.

PMID- 9159396
TI  - Distribution of pre-mRNA splicing factors at sites of RNA polymerase II
      transcription.
AB  - If pre-mRNA splicing begins during RNA synthesis, then transcriptionally active
      genes may be expected to contain high concentrations of pre-mRNA splicing
      factors. However, previous studies have localized splicing factors to a network
      of "speckles," which is distinct from individual sites of gene transcription
      where pre-mRNA is spliced. Speckles have been detected with antibodies specific
      for splicing snRNPs and members of the SR family of splicing factors. Here we
      report that dilution of these probes results in the visualization of hundreds of
      sites throughout the HeLa cell nucleus, the size and distribution of which are
      consistent with transcription units viewed with light microscopy. Importantly,
      these sites of highest SR protein concentration frequently coincide in three
      dimensional space with active sites of RNA polymerase II transcription. A newly
      developed reagent specific for a single member of the SR family, SRp20, detects a
      subset (approximately 20%) of these sites, suggesting the gene-specific
      accumulation of these splicing regulators, which have distinct functions in pre
      mRNA splicing. These observations question the view that the nucleus and its
      functions are highly compartmentalized; instead, they support a model in which
      the localization of these and possibly other gene regulators is determined
      primarily by their function.

PMID- 9159397
TI  - Dynamic, mitotic-like behavior of a bacterial protein required for accurate
      chromosome partitioning.
AB  - The Bacillus subtilis spo0J gene is required for accurate chromosome partitioning
      during growth and sporulation. We have characterized the subcellular localization
      of Spo0J protein by immunofluorescence and, in living cells, by use of a spo0J
      gfp fusion. We show that the Spo0J protein forms discrete stable foci usually
      located close to the cell poles. The foci replicate in concert with the
      initiation of new rounds of DNA replication, after which the daughter foci
      migrate apart inside the cell. This migration is independent of cell length
      extension, and presumably serves to direct the daughter chromosomes toward
      opposite poles of the cell, ready for division. During sporulation, the foci move
      to the extreme poles of the cell, where they function to position the oriC region
      of the chromosome ready for polar septation. These observations provide strong
      evidence for the existence of a dynamic, mitotic-like apparatus responsible for
      chromosome partitioning in bacteria.

PMID- 9159398
TI  - Regulation of Escherichia coli cell envelope proteins involved in protein folding
      and degradation by the Cpx two-component system.
AB  - We show that the two-component signal transduction system of Escherichia coli,
      CpxA-CpxR, controls the expression of genes encoding cell envelope proteins
      involved in protein folding and degradation. These findings are based on three
      lines of evidence. First, activation of the Cpx pathway induces 5- to 10-fold the
      synthesis of DsbA, required for disulfide bond formation, and DegP, a major
      periplasmic protease. Second, using electrophoretic mobility shift and DNase I
      protection assays, we have shown that phosphorylated CpxR binds to elements
      upstream of the transcription start sites of dsbA, degP, and ppiA (rotA), the
      latter coding for a peptidyl-prolyl cis/trans isomerase. Third, we have
      demonstrated increased in vivo transcription of all three genes, dsbA, degP, and
      ppiA, when the Cpx pathway is activated. We have identified a putative CpxR
      consensus binding site that is found upstream of a number of other E. coli genes.
      These findings suggest a potentially extensive Cpx regulon including genes
      transcribed by sigma70 and sigma(E), which encode factors involved in protein
      folding as well as other cellular functions.

PMID- 9159399
TI  - The sigma(E) and the Cpx signal transduction systems control the synthesis of
      periplasmic protein-folding enzymes in Escherichia coli.
AB  - In Escherichia coli, the heat shock-inducible sigma-factor sigma(E) and the Cpx
      two-component signal transduction system are both attuned to extracytoplasmic
      stimuli. For example, sigma(E) activity rises in response to the overproduction
      of various outer-membrane proteins. Similarly, the activity of the Cpx signal
      transduction pathway, which consists of an inner-membrane sensor (CpxA) and a
      cognate response regulator (CpxR), is stimulated by overproduction of the outer
      membrane lipoprotein, NlpE. In response to these extracytoplasmic stimuli,
      sigma(E) and CpxA/CpxR stimulate the transcription of degP, which encodes a
      periplasmic protease. This suggests that CpxA/CpxR and sigma(E) both mediate
      protein turnover within the bacterial envelope. Here, we show that CpxA/CpxR and
      sigma(E) also control the synthesis of periplasmic enzymes that can facilitate
      protein-folding reactions. Specifically, sigma(E) controls transcription of fkpA,
      which specifies a periplasmic peptidyl-prolyl cis/trans isomerase. Similarly, the
      Cpx system controls transcription of the dsbA locus, which encodes a periplasmic
      enzyme required for efficient disulfide bond formation in several
      extracytoplasmic proteins. Taken together, these results indicate that sigma(E)
      and CpxA/CpxR are involved in regulating both protein-turnover and protein
      folding activities within the bacterial envelope.

PMID- 9159400
TI  - The Rhizobium meliloti PII protein, which controls bacterial nitrogen metabolism,
      affects alfalfa nodule development.
AB  - Symbiotic nitrogen fixation involves the development of specialized organs called
      nodules within which plant photosynthates are exchanged for combined nitrogen of
      bacterial origin. To determine the importance of bacterial nitrogen metabolism in
      symbiosis, we have characterized a key regulator of this metabolism in Rhizobium
      meliloti, the uridylylatable P(II) protein encoded by glnB. We have constructed
      both a glnB null mutant and a point mutant making nonuridylylatable P(II). In
      free-living conditions, P(II) is required for expression of the ntrC-dependent
      gene glnII and for adenylylation of glutamine synthetase I. P(II) is also
      required for efficient infection of alfalfa but not for expression of
      nitrogenase. However alfalfa plants inoculated with either glnB mutant are
      nitrogen-starved in the absence of added combined nitrogen. We hypothesize that
      P(II) controls expression or activity of a bacteroid ammonium transporter
      required for a functional nitrogen-fixing symbiosis. Therefore, the P(II) protein
      affects both Rhizobium nitrogen metabolism and alfalfa nodule development.

PMID- 9159401
TI  - Antibiotic-induced endotoxin release from bacteria and its clinical significance.

PMID- 9159402
TI  - Polymerase chain reaction test for differentiation of five toxin types of
      Clostridium perfringens.
AB  - In order to avoid the use of experimental animals, the polymerase chain reaction
      (PCR) method was applied to differentiate Clostridium perfringens into five toxin
      types. Twenty-two out of 23 strains tested produced the toxin(s) corresponding to
      the toxin gene(s) identified by PCR, and vice versa. Consequently, the gene
      typing was consistent with conventional typing by animal tests. Twenty-five
      strains were identified as types different from original ones by the PCR method
      as well as a toxin neutralization test. These findings suggest that the PCR
      method, which is easy and timesaving, is applicable to identify the toxin types
      of C. perfringens as an alternative to animal tests, and that beta-, epsilon- and
      iota-toxin genes might be lost by long-term preservation. The reasons why the
      strains lost the genes are discussed.

PMID- 9159403
TI  - Thiadiazole derivatives: highly potent and selective inhibitors of human
      immunodeficiency virus type 1 (HIV-1) replications in vitro.
AB  - We have recently reported that thiadiazole (TDA) derivatives are highly potent
      inhibitors of human immunodeficiency virus type 1 (HIV-1) replication. These
      compounds belong to the family of nonnucleoside reverse transcriptase inhibitors
      (NNRTIs). In an attempt to develop more effective and pharmacologically favorable
      compounds, novel TDA derivatives have been synthesized and examined for their
      anti-HIV-1 activity in vitro. Among them, RD4-2217 was found to be the most
      potent inhibitor of HIV-1 replication. It inhibited replication of the HTLV-IIIB
      strain in MT-4 cells at a concentration of 6 nM. RD4-2217 was also inhibitory to
      clinical isolates and zidovudine-resistant mutants of HIV-1. The combination of
      RD4-2217 with zidovudine or the protease inhibitor A-75925 synergistically
      inhibited HIV-1 replication. Studies on the emergence of drug-resistant mutants
      revealed that, although much higher concentrations (1-10 microM) were required,
      RD4-2217 completely suppressed the breakthrough of HIV-1 in the supernatants
      during long-term culturing of infected cells. Furthermore, RD4-2217 at low
      concentrations (10 or 100 nM), in combination with zidovudine, also completely
      inhibited viral breakthrough. In addition, RD4-2217 had lower lipophilicity and
      improved protein binding as compared to its congener RD4-2024 and loviride. These
      results suggest that RD4-2217, one of the TDA derivatives, is worth pursuing as a
      candidate drug for the treatment of HIV-1 infections.

PMID- 9159405
TI  - Normal human fibroblasts immortalized by introduction of human papillomavirus
      type 16 (HPV-16) E6-E7 genes.
AB  - This report demonstrates that normal human fibroblasts can be immortalized by the
      introduction of HPV-16 E6-E7 genes. We designed zinc-inducible expression
      plasmids with HPV-16 E6, E7 or both. Each plasmid was introduced into normal
      human fibroblasts (TIG-3 cells) using lipofection methods. Only transfectants
      with the HPV-16 E6-E7 zinc-inducible expression plasmid, which were cultured in
      medium supplemented with 100 microM ZnSO4, overcame crisis and could be cultured
      over 200 population doubling levels (PDLs). These cell lines showed the
      reactivation of telomerase after crisis, and morphological alterations were also
      observed.

PMID- 9159404
TI  - Breast milk is not a significant source for early Epstein-Barr virus or human
      herpesvirus 6 infection in infants: a seroepidemiologic study in 2 endemic areas
      of human T-cell lymphotropic virus type I in Japan.
AB  - In order to evaluate the possibility of Epstein-Barr virus (EBV) and human
      herpesvirus 6 (HHV-6) transmission via breast milk, a total of 331 serum
      specimens collected from bottle-fed and breast-fed children and their mothers, in
      2 endemic areas of human T-cell lymphotropic virus type I (HTLV-I) in Japan, were
      assayed for antibodies to EBV and HHV-6. The seroprevalences of EBV and HHV-6
      were over 95% both in the mothers of bottle-fed children and in those of breast
      fed children. The seroprevalence of EBV at 12-23 months of age was 54.5% (36/66)
      and 55.8% (24/43) in breast-fed children and bottle-fed children, respectively.
      The seroprevalence of HHV-6 at 12-23 months of age was 90.9% (60/66) and 93.0%
      (40/43) in breast-fed children and bottle-fed children, respectively. No
      difference was observed between the seroprevalences of EBV and HHV-6 in breast
      fed and bottle-fed children at 12-23 months of age. Our seroepidemiologic data
      indicate that breast milk is not a significant source of early EBV or HHV-6
      infection in infancy.

PMID- 9159406
TI  - Unique expression of HRF20 (CD59) in human nervous tissue.
AB  - Damage to autologous tissue by complement is limited by several widely
      distributed membrane-associated glycoproteins which restrict the action of the
      complement in homologous species. These include decay accelerating factor (DAF),
      membrane cofactor protein (MCP) and 20 kDa homologous restriction factor
      (HRF20,CD59). Using immunohistochemical techniques, we examined the localization
      of these proteins in the central nervous system (CNS) and peripheral nervous
      system (PNS) using non-neurological human nervous tissue since some complement
      components have been demonstrated to be synthesized in the CNS. There was no
      evidence of parenchymal staining by anti-DAF or anti-MCP antibodies in either
      type of tissue except for the staining of the endothelium in capillaries. On the
      other hand, anti-HRF20 antibody clearly stained myelinated axons in the CNS as
      well as Schwann cells in the PNS. In addition, we detected positive staining by
      anti-DAF antibody in the PNS of a Paroxysmal nocturnal hemoglobinuria (PNH)
      patient who is genetically deficient in HRF20.

PMID- 9159407
TI  - Presence of IgM antibodies which sensitize HIV-1-infected cells to cytolysis by
      homologous complement in long-term survivors of HIV infection.
AB  - Although human cells are resistant to homologous human complement due to the
      presence of species-specific membrane inhibitors, a naturally occurring IgM
      antibody which recognizes an asialo-oligosaccharide can sensitize HIV-1-infected
      cells for complement-mediated cytolysis. Therefore, we investigated whether long
      term survivors of HIV-1 infection harbor such antibodies in their sera. Thirty of
      31 sera from HIV-1 seropositive hemophilia patients who have survived HIV-1
      infection 10 years or more showed appreciable cytolytic activity, while only 2
      sera of 10 seropositive patients presumed to have been infected with HIV-1 (due
      to sexual contact) more recently showed cytolytic activity. On the other hand,
      only 7 out of 43 sera from seronegative hemophilia patients showed cytolytic
      activity. Immunofluorescence staining for IgM on HIV-1-infected cells essentially
      correlated with the cytolytic capacity of the sera. Therefore, naturally
      occurring IgM antibodies and/or generated IgM antibodies reactive with the HIV-1
      infected cells in patients might have been responsible for long-term survival due
      to complement-mediated immune cytolysis which may, in conjunction with cytotoxic
      T lymphocytes, synergistically suppress the infected cells in vivo. Therefore,
      the transfusion of such IgM antibodies could be effective for the treatment of
      HIV-1-infected individuals.

PMID- 9159408
TI  - Further clonal expansion of T cells upon rechallenge of superantigen
      staphylococcal enterotoxin A.
AB  - Superantigens are known to induce clonal anergy and/or deletion in reactive T
      cells peripherally. This study was undertaken to investigate the T-cell status
      early after exposure to staphylococcal enterotoxin A (SEA) in vivo and in vitro.
      At the peak of clonal expansion following the administration of 5 microg SEA
      (i.e., 2 days after the injection), C57BL/6 mice were rechallenged with the same
      dose of SEA in vivo. The secondary stimulation augmented clonal expansion of the
      T cells bearing Vbeta3 and Vbeta11 in both CD4+ and CD8+ populations. In vitro
      restimulation of the spleen cells taken from the SEA-primed mice also induced
      further expansion of the Vbeta3+ T cells during 2 days of culturing, whereas
      without restimulation, a marked reduction of Vbeta3+ T cells occurred. The spleen
      cells from the SEA-primed mice were hyper-reactive to in vitro restimulation with
      SEA as measured by 3H-TdR uptake on day 1 of culturing, but augmented
      proliferation leveled off thereafter. By day 3, the values of 3H-TdR uptake were
      less than 20% of those of the controls in which spleen cells from native mice
      were stimulated with SEA in vitro. These results suggest that T cells exposed to
      SEA in vivo are still capable of proliferating upon SEA rechallenge, but
      subsequently, the proliferation starts to wane.

PMID- 9159409
TI  - Identification of murine T cells reactive with the bacterial superantigen
      Yersinia pseudotuberculosis-derived mitogen (YPM) and factors involved in YPM
      induced toxicity in mice.
AB  - We previously reported that Yersinia pseudotuberculosis-derived mitogen (YPM)
      acts as a superantigen to human T cells. In this study, we assessed the
      superantigenicity and toxicity of YPM using murine experimental models. YPM
      activated T cells to produce interleukin-2 in a major histocompatibility complex
      class II molecule-dependent manner. The T-cell blasts induced by YPM expressed T
      cell receptor (TCR) beta-chain variable region (Vbeta)7, Vbeta8.1, Vbeta8.2 and
      Vbeta8.3. The injection of YPM into mice pre-sensitized with D-galactosamine
      induced lethal shock. This shock was blocked by the injection of monoclonal
      antibodies (mAbs) to CD4, TCR Vbeta7 plus Vbeta8, tumor necrosis factor-alpha
      (TNF-alpha) and interferon-gamma (IFN-gamma), but not by injection to CD8 or
      unrelated Vbeta. These results indicate that YPM-induced shock requires the
      presence of CD4+ T cells bearing TCR Vbeta7 and Vbeta8, and that endogenous TNF
      alpha and IFN-gamma mediate the lethal effects.

PMID- 9159410
TI  - Analysis of cytokine producing activity of intestinal intraepithelial T cells
      from TCR beta-chain and delta-chain mutant mice.
AB  - Intestinal intraepithelial T cells (IELs) expressing either gammadelta TCR or
      alphabeta TCR have been proposed to play an important role in the regulation of
      intestinal epithelia by producing cytokines that directly influence the adjoining
      intestinal epithelial cell (IEC) functions. To illuminate this issue, we utilized
      TCR mutant mice to obtain gammadelta IELs, alphabeta IELs and mixed gammadelta
      and alphabeta IELs from corresponding alphabeta T-cell-deficient (beta-/-),
      gammadelta T-cell-deficient (delta-/-) and wild-type (WT) littermate mice. The
      production of IFN-gamma by these IELs as well as the mRNA for IFN-gamma, TGF
      alpha, TGF-beta1, TNF-alpha and TNF-beta in these IELs, in conjunction with the
      effect of produced cytokines on the expression of class II MHC molecules by the
      in vitro cell line IEC-6, were investigated. IFN-gamma and TNF-alpha [corrected]
      specific mRNA were detectable in all freshly isolated gammadelta, alphabeta and
      WT IELs. In addition to the IFN-gamma and TNF-alpha [corrected] mRNA, alphabeta
      and WT IELs that had been activated in culture plates coated with anti-CD3 mAb
      contained mRNA for TGF-beta1 and TNF-beta proteins. In the cultured gammadelta
      IELs, however, the signals for IFN-gamma and TNF-alpha [corrected] transcripts
      were weak, and mRNA for the latter two cytokines was almost undetectable.
      Supernatants from in vitro culturing of alphabeta and WT IELs but not gammadelta
      IELs induced class II MHC gene expression in IEC-6, whereas, in the presence of
      anti-IFN-gamma mAb, the same culture supernatants failed to do so. In fact, the
      concentration of IFN-gamma in supernatants from alphabeta and WT IEL cultures was
      ten- to twentyfold higher than that in the supernatant from the gammadelta IEL
      culture. Finally, TGF-alpha specific mRNA was not detectable in the gammadelta
      and alphabeta IELs even after in vitro activation. These results indicate that
      alphabeta IELs are superior to gammadelta IELs in the ability to produce IFN
      gamma, TGF-beta1, TNF-alpha [corrected] and TNF-beta through TCR crosslinking
      primary in vitro stimulation.

PMID- 9159411
TI  - Experimental Helicobacter pylori infection in association with other bacteria.
AB  - We performed surgical treatment on normal ddY mice before Helicobacter pylori
      inoculation. The treatment was expected to obstruct bacterial flow out of the
      stomach and increase the chance of bacterial attachment to the gastric epithelium
      in mice. The bacterial challenge induced inflammation in the stomach. H. pylori
      was recovered from the stomach throughout the observation period. Lactobacilli
      and streptococci tended to relate to the increase in number of H. pylori
      recovered. Pretreatment with atropine was considered to confuse the gastric flora
      and affect the number of H. pylori recovered. These results suggested that a
      certain amount of time is necessary for H. pylori to contact with the gastric
      epithelium and that the composition of flora is important for the establishment
      of H. pylori infection.

PMID- 9159412
TI  - Synovial mononuclear cells consist with T cells which produce high levels of
      tumor necrosis factor alpha.
AB  - To determine whether synovial mononuclear cells include a population of tumor
      necrosis factor alpha-producing T cells, we measured tumor necrosis alpha levels
      in culture supernatants of synovial mononuclear cells by ELISA and analyzed tumor
      necrosis alpha mRNA-positive cell frequencies. There were no significant
      differences in the spontaneous levels of TNF alpha between synovial mononuclear
      cells and peripheral mononuclear cells. The frequency of tumor necrosis factor
      alpha mRNA-positive cells in synovial mononuclear cells was higher than that of
      peripheral mononuclear cells. When stimulated with a superantigen, mononuclear
      cells from the synovial fluid of rheumatoid arthritis patients showed higher
      levels of tumor necrosis factor alpha production (1,035 +/- 817 pg/ml) than did
      mononuclear cells from their peripheral blood (236 +/- 180 pg/ml). In addition,
      we observed that a few T cell clones were resistant to superantigenic
      restimulation in vitro. We conclude that when these types of T cells persist in
      the synovium, they play a role in the development of rheumatoid arthritis via a
      mechanism involving tumor necrosis factor alpha production.

PMID- 9159413
TI  - Antibodies are generated during infection to Coxiella burnetii macrophage
      infectivity potentiator protein (Cb-Mip).
AB  - Antisera from rabbits immunized with formalin inactivated Coxiella burnetii
      isolates associated with either acute (Nine Mile, phase I or phase II) or chronic
      (Priscilla) Q fever showed reactivity to a C. burnetii macrophage infectivity
      potentiator protein (Cb-Mip) cloned in Escherichia coli. Further, antisera
      generated in BALB/c mice after infection with live Nine Mile phase I or Priscilla
      isolates also showed reactivity to Cb-Mip by immunoblot analysis. In addition,
      human serum from an individual with previous serological and clinical evidence of
      Q fever showed reactivity to Cb-Mip. This study indicates that Cb-Mip is
      immunogenic in both experimental and natural infections, and is the first report
      on the presence of antibodies to Mip/Mip-like proteins of intracellular bacteria
      in human sera. Cb-Mip may serve as a potential target antigen for developing
      recombinant vaccines or diagnostic assays for Q fever.

PMID- 9159414
TI  - Leptin: a hormone of reproduction.

PMID- 9159415
TI  - Are we overlooking (auto) immune ovarian infertility?

PMID- 9159416
TI  - Immunological causes of ovarian infertility and repeated implantation failure-
      two aspects of the same problem?

PMID- 9159417
TI  - Analysis of human sperm-derived pronuclei by three-colour fluorescent in-situ
      hybridization.
AB  - We describe a modification of the human sperm-zona-free hamster egg fusion method
      that permits the study of aneuploidy in sperm-derived pronuclei by multicolour
      fluorescent in-situ hybridization (FISH). Zona-free hamster eggs and human
      spermatozoa were fused and cultured for 15 h in the presence of colcemid (1
      microg/ml of medium) to obtain hamster oocytes arrested at metaphase II and human
      spermatozoa at the pronuclear stage. By applying a whole human genomic DNA probe
      we confirmed that 100% of pronuclei tested (372/372) were of human origin. One
      colour fluorescent in-situ hybridization using a centromeric 18 probe was applied
      to 919 pronuclei with different dithiothreitol (DTT) pretreatments: 50 mM (10
      min) or 25 mM (20 and 25 min). The highest hybridization efficiency was obtained
      with treatment with 25 mM DTT for 20 min (90.3%). Sex chromosome aneuploidy was
      analysed by three-colour FISH in a total of 2596 pronuclei from a normal donor.
      Hybridization efficiency was 98.6%. The disomy rates for X, Y and XY chromosomes
      (0.11, 0.04 and 0.08% respectively) were similar to data reported for sperm
      nuclei by three-colour FISH and to those obtained in sperm chromosomes. These
      results suggest that selection of potentially fertile spermatozoa (spermatozoa
      able to fertilize zona-free hamster eggs and produce a pronucleus) does not imply
      chromosomal selection.

PMID- 9159419
TI  - Tissue renin-angiotensin systems and reproduction.
AB  - The continued acquisition of information on the distribution of expression of
      components of the renin-angiotensin system shows that it has functions in the
      tissues that are quite unrelated to its systemic actions. In particular, both
      type 1 and type 2 angiotensin receptors are found in many tissues of the
      reproductive system of both sexes. In addition, the widespread occurrence of
      (pro)renin, angiotensin converting enzyme and angiotensinogen suggests that the
      generation of angiotensin II within the tissues occurs at sites close to its
      sites of action. The data suggest that angiotensin II operates as an important
      paracrine agent with profoundly significant roles in several functions of the
      reproductive system, and in fertility.

PMID- 9159418
TI  - Reversal of tubal sterilization using laparoscopically placed titanium staples:
      preliminary experience.
AB  - We tested the feasibility of performing outpatient laparoscopic surgery to
      reverse tubal sterilization using titanium staples to reapproximate the oviducts.
      A total of 14 women underwent the procedure which involved excision of the tubal
      eschar, stenting of the severed remnants, and circumferential stapling of the
      muscularis and serosa. Reapproximation was possible in all cases, with a measured
      tubal length post-anastomosis of 4.5 +/- 0.5 cm (range 3.0-7.0 cm). The length of
      operating time was 2.8 +/- 0.2 h (range 2.2-3.8 h), and all patients were
      discharged the same day. There were no operative complications, and no
      readmissions were necessary. Within 6 months of surgery there were six
      pregnancies including one spontaneous abortion and five ongoing pregnancies. Of
      those not conceiving within 8 months, seven (100%) demonstrated tubal patency on
      a follow-up hysterosalpingogram. We conclude the laparoscopic approach to tubal
      sterilization reversal is a viable alternative to open abdominal microsurgical
      approaches. Although preliminary, laparoscopic surgery promises to be cost
      effective, as it can be performed on an outpatient basis, may reduce operative
      time and minimizes the recuperative period of patients.

PMID- 9159420
TI  - Gonadotrophin-releasing hormone agonist therapy for hirsutism is as effective as
      high dose cyproterone acetate but results in a longer remission.
AB  - Both cyproterone acetate (CPA) and the gonadotrophin-releasing hormone agonist
      (GnRHa) have been shown to be effective for the treatment of hirsutism. We wished
      to compare the effectiveness of CPA in two standard doses with GnRHa and add-back
      therapy and to compare the length of remission after these treatments. A total of
      60 hirsute hyperandrogenic women was assigned to the following treatment groups:
      CPA 2 mg with 35 microg of ethinylestradiol for 21 days each month (Diane group),
      CPA 50 mg, days 5-15, and ethinylestradiol 50 microg, days 5-25, each month (CPA
      group) or Decapeptyl 3.75 mg i.m. every 28 days with the addition of conjugated
      oestrogen 0.625 mg, days 1-21, and medroxyprogesterone acetate 10 mg, days 12-21
      (GnRHa group). Hirsutism was graded by the Ferriman-Gallwey-Lorenzo (FGL) index
      and anagen hair shaft diameters and serum luteinizing hormone (LH) and
      testosterone were assessed before and every 3 months during and after treatment.
      All women were treated for 1 year with 1 year follow-up. At baseline hirsutism
      and endocrine patterns were similar in all groups. After one year of treatment,
      hirsutism decreased in all groups but the changes were greater (P <0.05) in the
      CPA and GnRHa groups than in the Diane group. Serum LH and testosterone were
      lowest in the GnRHa group. After withdrawal, hirsutism increased rapidly in the
      Diane and CPA groups and after 6 months, FGL scores and hair shaft diameters were
      similar to pretreatment values. In the GnRHa group, hirsutism increased more
      gradually and after 1 year of withdrawal, FGL scores and hair diameters were
      significantly (P <0.05) less than pretreatment values. Serum LH and testosterone
      increased rapidly in all three groups reaching pretreatment values by 6 months.
      These data suggest equal efficacy of the GnRHa and the high dose CPA regimen for
      the treatment of hirsutism in hyperandrogenic women. GnRHa with add-back
      treatment appears to result in a longer remission of hirsutism in comparison with
      CPA.

PMID- 9159421
TI  - Undetected gynaecological disorders in women with renal disease.
AB  - Women with chronic renal disease (CRD) who are on dialysis or have a functioning
      renal transplant are typically stoical in their attitude towards other health
      problems. We undertook a prospective study of 100 women with CRD to assess the
      prevalence of gynaecological disorders in this group of patients. Assessment
      included the measurement of follicle stimulating hormone, luteinizing hormone,
      prolactin and oestradiol concentrations, cervical cytology and a pelvic
      ultrasound scan. We found that gynaecological problems are highly prevalent and
      frequently unrecognized. Of these women, 58% had a menstrual disorder, with
      uncontrolled menorrhagia being a significant problem when it aggravated the
      chronic anaemia of renal disease, and 35% were menopausal, including seven women
      under the age of 40 years. Menopausal symptoms were undertreated. We identified a
      14-fold increase in premature ovarian failure secondary to CRD and the use of
      cyclophosphamide therapy. In all, 22% of the women were subfertile and 10% had an
      abnormal smear, with cervical dyskariosis being significantly increased because
      of long-term immunosuppression. Contraceptive advice had often been absent or
      inappropriate. We conclude that formal gynaecological review should be routinely
      available for women with CRD.

PMID- 9159422
TI  - A somatostatin analogue decreases embryonic loss following superovulation in rats
      by normalizing insulin-like growth factor-I action in the uterus.
AB  - This study was designed to determine whether the somatostatin analogue,
      octreotide, could prevent embryonic loss by normalizing increased uterine insulin
      like growth factor-I (IGF-I) action related to hyperoestrogenaemia following
      superovulation. Superovulated immature and oestradiol-17beta-treated adult rats
      were infused with 100 or 300 microg/ml of octreotide respectively, or injected
      daily with 1 or 10 microg of octreotide from day 1 to day 3 of pregnancy. On day
      3, embryos were collected from the oviducts and uteri. Uterine luminal fluid was
      subjected to embryo culture. The amounts of uterine IGF-I and IGF binding
      proteins (IGFBP) were determined by radioimmunoassay and ligand binding assay
      respectively. Octreotide infusion normalized uterine IGF-I action following
      superovulatory and oestradiol-17beta treatment, by reducing IGF-I concentrations
      and increasing IGFBP concentrations. Octreotide infusion increased the number of
      normal embryos by 2.7-fold and 1.7-fold in superovulated and oestradiol-17beta
      treated rats respectively, and reversed the detrimental effects of uterine
      luminal fluid on embryonic development caused by superovulatory and oestradiol
      17beta treatment. Daily injections with octreotide had similar but reduced
      effects in all parameters examined in both treatment groups. In conclusion,
      octreotide may reduce embryonic loss, at least in part, by normalizing IGF-I
      action following superovulation.

PMID- 9159423
TI  - A cytokine switch induced by human seminal plasma: an immune modulation with
      implications for sexually transmitted disease.
AB  - The immunosuppressive activity of human seminal plasma may be one factor in the
      aetiology of sexually transmitted disease and could be particularly important for
      the spread of human immunodeficiency virus (HIV). The advent of virus that can
      preferentially infect Langerhans cells of the genital mucosa underscores the
      relevance of seminal plasma effects. Virally infected cells are eradicated by the
      killing activity of T cells and natural killer (NK) cells and this cytotoxicity
      is stimulated by IL-12 (previously known as natural killer cell stimulatory
      factor) and partly inhibited by IL-10 (previously known as cytokine synthesis
      inhibitory factor). We have examined the effects of human seminal plasma on the
      production of these key cytokines. Cytokine production was measured in rapidly
      diluted, fresh, lipopolysaccharide (LPS)-stimulated, whole blood since this
      provided leukocytes with minimal exposure to prostaglandin. Prostaglandin
      concentrations and cytokine release were measured by ELISA. Addition of human
      seminal plasma diluted up to 100,000 times (0.001%) to blood cell cultures led to
      a marked increase in the IL-10/IL-12 ratio (P <0.02). A dose-dependent increase
      in the ratio was observed in five separate experiments, from a control value of 1
      (no seminal plasma) to a mean value of 80 (1% seminal plasma). This cytokine
      switch was also seen when seminal plasma was substituted by pure prostaglandin E
      (PGE) and 19-OH PGE (the main prostaglandin constituent of human seminal plasma).
      Lipid-extracted seminal plasma was considerably less active at high dilutions
      than whole seminal plasma at the same dilution. However, its activity could be
      restored by the addition of synthetic PGE and 19-hydroxy PGE. A stimulation of IL
      10 and a decrease in IL-12 in host-defence cells of the lower female reproductive
      tract will seriously affect the ability of cytotoxic T cells and NK cells to
      recognise and destroy virally infected cells. In addition, the stimulation of IL
      10 will inhibit the release of the anti-HIV activity from CD8+ve cells. The
      cytokine switch reported here, activated by semen deposition, would exercise a
      key inhibitory control over vital immune defences in the lower genital tract,
      with ablation of cell-mediated responses and immunosurveillance.

PMID- 9159424
TI  - Determination of the parent of origin in nine cases of prenatally detected
      chromosome aberrations found after intracytoplasmic sperm injection.
AB  - Prenatal cytogenetic analysis of 71 fetuses conceived by intracytoplasmic sperm
      injection (ICSI) resulted in the detection of nine (12.7%) chromosome aberrations
      including two cases of 47,XXY, four cases involving a 45,X cell line and three
      autosomal trisomies. Molecular analysis of the parental origin of the deleted or
      supernumerary chromosome was performed by using polymorphic microsatellite
      markers. Six cases involving a sex chromosome abnormality were found to be of
      paternal origin while the two trisomic cases that could be analysed were of
      maternal origin. Two cases involved the same infertile couple who had two
      consecutive ICSI pregnancies terminated because of a chromosome abnormality. The
      replaced embryos in both cases originated from a single batch of ICSI fertilized
      oocytes of which part was used to initiate the first pregnancy and part was
      cryopreserved and used to initiate the second pregnancy.

PMID- 9159425
TI  - Microdeletions of the Y chromosome and intracytoplasmic sperm injection: from
      gene to clinic.
AB  - Intracytoplasmic sperm injection (ICSI) is a successful treatment option for
      severe male infertility, although the aetiology of the disorder remains unclear
      in most cases. Recently, microdeletions in the AZF region of the Y chromosome
      have been detected in men with azoospermia or severe oligozoospermia. In this
      study we investigated the prevalence of microdeletions in the AZF region of the Y
      chromosome in a population of men undergoing ICSI, and looked for clinical
      characteristics of men with and without this deletion. Blood was drawn from 164
      men, who were on the waiting list for ICSI treatment: 19 were azoospermic, 111
      oligozoospermic and 34 normozoospermic (after previous total fertilization
      failure). A total of 100 men with proven fertility served as a control.
      Microdeletions in the AZFc region were present in seven of the 111
      oligozoospermic men (6.3%). Compared with oligozoospermic men without
      microdeletions, men with microdeletions had a lower concentration of follicle
      stimulating hormone (FSH), a lower number of motile spermatozoa and a lower
      frequency of abnormal findings at andrological history or examination. No
      microdeletions were found in the azoospermic, normozoospermic and control groups.
      In conclusion, microdeletions in the AZFc region are relatively frequently found
      in men with severe unexplained oligozoospermia. In the ICSI era this finding has
      an important impact because this form of male infertility is now potentially
      hereditary. Therefore we recommend DNA screening (and genetic counselling) before
      ICSI, especially in men with normal FSH, severe oligozoospermia and no abnormal
      clinical andrological findings.

PMID- 9159426
TI  - Proximal tubal occlusion: is there an alternative to microsurgery?
AB  - Fertility outcome following microsurgical tubocornual anastomosis by laparotomy
      was evaluated. A total of 131 women presenting pure proximal occlusion, whether
      bilateral or in one tube only, were treated between January 1978 and December
      1993. Subsequent fertility was studied in 120 patients, 11 being patients lost to
      follow-up. Cumulative intrauterine pregnancy (IUP) rate, evaluated by life-table
      analysis, was 68% at 24 months. The overall IUP rate, calculated from a group of
      120 women with follow-up > or = 2 years, and including births and miscarriages,
      was 70% after 2 years. Comparisons of the cumulative IUP rates show that the
      fertility outcome is significantly better if the woman is aged < or = 36 years
      and if tubocornual anastomosis is carried out bilaterally. These results from our
      personal series confirm that microsurgical tubocornual anastomosis is still of
      prime importance in the treatment of pure proximal occlusions. Nevertheless,
      considerable progress in the fields of tubal catheterization, Falloposcopy and in
      vitro fertilization techniques raises the question of the management of patients
      presenting with a proximal tubal occlusion. Here we define the indications for
      microsurgical tubocornual anastomosis.

PMID- 9159427
TI  - The optimal number of embryos to be transferred in shared oocyte donation:
      walking the thin line between low pregnancy rates and multiple pregnancies.
AB  - There has been growing concern about the number of multiple gestations resulting
      from assisted reproductive technologies. For in-vitro fertilization (IVF), there
      are guidelines concerning the number of embryos to be transferred. In oocyte
      donation, however, there is a paucity of studies addressing this issue and common
      practice is extrapolated from standard IVF procedures. This may not be correct
      since endometrial receptivity has been shown to be altered in oocyte donation.
      Thus the purpose of this study was to assess the optimal number of embryos to be
      transferred in oocyte donation. The study population included 254 patients with
      ovarian failure who underwent a total of 601 embryo transfers in a single shared
      oocyte donation programme. Pregnancy rates (PRs), multiple pregnancies, triplet
      pregnancy rates, and implantation rates were evaluated according to the number of
      embryos transferred. A significant linear increase in PRs was noted with the
      increasing number of embryos transferred up to five (11.1% for one embryo, 36.7%
      for five embryos). Multiple pregnancies increased significantly from 15.8% for
      two embryos transferred, to 44.4% for five embryos. The rate of triplet
      pregnancies also increased from 2.7% for three embryos transferred, to 8.3% for
      five embryos. Optimization of the number of embryos to be transferred is
      discussed.

PMID- 9159428
TI  - Recurrence of hydrosalpinges after transvaginal aspiration of tubal fluid in an
      IVF cycle with development of a serometra.
AB  - The presence of hydrosalpinges has been shown to be deleterious in infertility
      treatment. Pregnancy rates after in-vitro fertilization (IVF) with embryo
      transfer decline considerably. This study concerns a patient who developed
      bilateral hydrosalpinges during controlled ovarian stimulation in preparation for
      IVF treatment. Transvaginal aspiration of the tubal fluid was unsuccessful as the
      tubes refilled within 2 days. Additionally, on the day of embryo transfer a
      serometra developed which could not be seen on the day of oocyte retrieval. The
      uterine cavity was evacuated via an embryo transfer catheter and three embryos
      were transferred. The serometra reappeared 3 days after embryo transfer. A
      pregnancy could not be achieved. The accumulation of fluid in the uterine cavity
      during an IVF/embryo transfer cycle is a rare complication of hydrosalpinges.
      However, the retrograde flow of tubal fluid may disturb intrauterine embryo
      development. This study suggests that the aspiration of hydrosalpinges and
      intrauterine fluid accumulation during an IVF cycle is not beneficial, as the
      underlying pathology is not cured. Cancellation of the treatment cycle or
      cryopreservation of oocytes in the pronucleate stage and transfer of the
      cryopreserved oocytes after surgical correction of the tubes may be better
      options.

PMID- 9159429
TI  - Clomiphene citrate as a possible cause of a psychotic reaction during infertility
      treatment.
AB  - Secondary side-effects often occur in women undergoing hormonal stimulation
      treatment with clomiphene citrate. In general 10.4% of women experience hot
      flushing, 5.5% have complaints caused by enlargement of the ovaries and 3.5%
      experience central nervous symptoms (nervousness, sleeplessness, headaches,
      visual disturbances, vertigo). During ovarian stimulation with clomiphene citrate
      for in-vitro fertilization, a 32 year old patient developed psychotic symptoms,
      commencing 3 days after initiation of treatment. Hospitalization in the
      psychiatric ward became necessary when severe formal and rational thought
      disturbances arose together with perceptory and sensory delusions. Under
      neuroleptic treatment the symptoms improved. Nevertheless, follow-up psychiatric
      care on an outpatient basis was deemed necessary. The infertility treatment was
      continued with human menopausal gonadotrophin stimulation. Psychiatric
      instability occurred neither at this point nor during the 2 year follow-up
      observation period. Both an exogenous psychosis (ICD F23.9) as well as the
      exacerbation of an endogenous psychosis (ICD F29) may be considered for the
      differential diagnosis. The stimulation with clomiphene citrate in connection
      with the physical and psychic stress of the infertility therapy can be regarded
      as the trigger factor. For patients with evidence of psychiatric illness in their
      case history, ovulation-inducing substances such as clomiphene citrate should be
      implemented with particular care.

PMID- 9159430
TI  - Hormonal profile, endometrial histology and ovarian ultrasound assessment during
      1 year of nomegestrol acetate implant (Uniplant).
AB  - The present study assesses the endocrinological, endometrial histology and
      vaginal ultrasound profiles of nomegestrol acetate subdermal implant users at
      varying times after insertion. Follicle stimulatory hormone, luteinizing hormone,
      oestradiol, progesterone, vaginal ultrasound assessment of the ovaries and the
      histological dating of the endometrium were serially assessed for a period of 50
      days immediately after the insertion, and after at 6 months and 12 months of use.
      The endocrinological results of this prospective observational clinical trial
      indicated that 75% of the cycles across the study period in Uniplant users were
      anovulatory, 63% showing development of a persistent non-luteinized follicle.
      Anovulatory cycles devoid of follicular development were seen primarily in the
      first months after Uniplant insertion. Ovulatory cycles represented 25% of the
      Uniplant cycles. Inadequate luteal phase or disregulation of follicular growth
      was a common feature of ovulatory cycles. In conclusion, these findings suggest
      that the contraceptive mechanisms of a single nomegestrol acetate subdermal
      implant involve prevention of follicular growth, development of a persistent non
      luteinized follicle, inadequate luteal phase and disruption of the endometrial
      architecture.

PMID- 9159431
TI  - Detection of human sperm acrosome reaction: comparison between methods using
      double staining, Pisum sativum agglutinin, concanavalin A and transmission
      electron microscopy.
AB  - The acrosome reaction is an important marker for human sperm function. Since
      different laboratory techniques may be used for the detection of this exocytotic
      process, the purpose of the present study was to compare three common markers
      [Pisum sativum agglutinin (PSA), concanavalin A (ConA), double staining] and
      transmission electron microscopy for identification of acrosomal changes.
      Preliminary findings had demonstrated that similar results were achieved with
      Trypan Blue and Hoechst 33258 staining. Therefore, supravital stainings were
      omitted. In various experiments, human spermatozoa were treated with two
      concentrations (10 and 3.3 microM) of calcium ionophore A23187 for 15, 30 and 60
      min after capacitation for 3 and 6 h at 37 degrees C. The percentages of
      spermatozoa with acrosomal loss detected by fluorescein isothiocyanate (FITC)
      ConA were consistently lower than those obtained by double staining or FITC-PSA,
      which showed comparable results. Following 6 h of capacitation and incubation
      with 10 microM ionophore for 1 h at 37 degrees C, 25.9 +/- 15.7% of all
      spermatozoa showed almost complete loss of the acrosomal content. Binding of FITC
      ConA to the acrosomal region was observed in 27.0 +/- 13.2% of spermatozoa
      obtained from the same sample. FITC-ConA and double staining or FITC-PSA detect
      different stages of the acrosome reaction and may be helpful for a differentiated
      evaluation of this sperm function.

PMID- 9159432
TI  - Artificial insemination and in-vitro fertilization using donor spermatozoa: a
      report on 15 years of experience.
AB  - Donor insemination (DI) using cryopreserved semen commenced at The Royal Women's
      Hospital in 1976. Over the next 15 years we performed 5953 treatment cycles to
      achieve 816 pregnancies (13.7% per cycle) and 706 live births. In-vitro
      fertilization (IVF) using donor spermatozoa commenced in 1986. Over the next 5
      years we performed 303 treatment cycles for 185 couples. Including subsequent
      transfer of cryopreserved embryos, a total of 33% of couples achieved a
      successful pregnancy by IVF. Statistical analysis indicated that, for DI
      pregnancies, the most important semen variable was the percentage post-thaw
      motility, whilst for normal fertilization in IVF it was the pre-freeze motility.
      These results may be explained by the compensatory effects of post-thaw
      processing of spermatozoa for IVF, but not for DI in our clinic.

PMID- 9159433
TI  - The in-vitro effects of nicotine and cotinine on sperm motility.
AB  - Swim-up spermatozoa from the seminal samples of non-smokers, usually not exposed
      to passive smoking, were treated in vitro with nicotine (NIC) and cotinine (COT)
      at the average levels found in smokers' seminal plasma and at levels 500 times
      higher than this average. This was done to evaluate the action of these drugs on
      sperm motility. Each sample was allowed to swim up in Tyrode's solution with or
      without the drug; the study was carried out at time 0 and +1, +2, +4, +8 and +24
      h of incubation, using a light microscope and a CASA system (experiment 1). In
      addition, the direct action of smoke on spermatozoa was studied using aspirated
      cigarette smoke (experiment 2). Kinetic parameters were then measured at 30 min,
      45 min and 60 min starting from the last smoke injection. The first experiment
      showed that NIC and COT at average levels did not produce statistically
      significant variations of the kinetic parameters studied up to 24 h. However, the
      much higher concentration significantly altered all the kinetic variables in
      relation to the time of incubation. The second experiment with smoke in toto
      demonstrated a sharp reduction in all the sperm kinetic parameters. This
      reduction was seen after 30 min exposure to smoke and increased progressively
      until almost complete immotility at 1 h of exposure. These results suggest that
      NIC and COT are not responsible for the harmful effects of cigarette smoke on
      sperm kinetic parameters reported in the literature.

PMID- 9159434
TI  - Fertilization and pregnancy using intentionally cryopreserved testicular tissue
      as the sperm source for intracytoplasmic sperm injection in 10 men with non
      obstructive azoospermia.
AB  - Testicular tissue extraction (TESE) to obtain spermatozoa for use with
      intracytoplasmic sperm injection (ICSI) has recently been employed in patients
      with non-obstructive azoospermia. Standard protocol is to retrieve a new sample
      of testis tissue on the day of oocyte recovery. Unfortunately, approximately 30%
      of men will possess no spermatozoa in their tissue, making ICSI an impossibility.
      We investigated whether testicular tissue that was intentionally obtained well
      before any planned ICSI cycle and cryopreserved could then serve as an
      efficacious sperm source in a subsequent ICSI cycle. This study reports on 10 men
      with non-obstructive azoospermia who did have spermatozoa found within their
      testis tissue at the time of TESE and who chose to use their frozen samples as
      the source of spermatozoa for a later cycle of ICSI. In 19 cycles the overall
      fertilization rate was 48%. Embryo transfer occurred in 89% of cycles. Two
      couples have achieved pregnancy (one ongoing, one delivered). All patients except
      one had multiple vials of frozen tissue remaining following their first cycle.
      This approach is offered as an alternative to repeated testicular tissue
      sampling, as the availability of spermatozoa is assured prior to the initiation
      of ovulation induction. This tissue can be harvested at the same time as
      diagnostic biopsy, thereby minimizing the number of surgical procedures.

PMID- 9159435
TI  - Evidence for regional differences of semen quality among fertile French men.
      Federation Francaise des Centres d'Etude et de Conservation des Oeufs et du
      Sperme humains.
AB  - The world literature on human semen quality indicates apparent geographical
      differences but these might primarily depend on variations among studies for
      subject recruitment strategy, semen analysis or data processing methods. A
      retrospective analysis on the quality of semen from 4710 healthy unselected
      fertile men, who were candidate semen donors to sperm banks in university
      hospitals in eight different French areas during the period 1973-1993, was
      undertaken. In these centres, all the men were referred under the same guidelines
      and all semen samples were analysed using similar methodologies. Significant
      differences were found between centres for seminal volume, sperm concentration,
      total number of spermatozoa in the ejaculate and percentage of motile spermatozoa
      (all P < 0.0001). Multiple regression analysis accounting for the age, sexual
      abstinence before semen collection and year of semen collection also showed
      regional differences: compared to Paris, the seminal volume was higher in Caen (P
      < 0.001) and lower in Toulouse (P < 0.01), the total number of spermatozoa was
      higher in Lille (P < 0.001) and lower in Toulouse (P < 0.05) and the percentage
      of motile spermatozoa was higher in Bordeaux and lower in Tours (both P < 0.001).
      This is the first study providing evidence for regional differences in the human
      semen quality.

PMID- 9159436
TI  - Physiological relationships between inhibin B, follicle stimulating hormone
      secretion and spermatogenesis in normal men and response to gonadotrophin
      suppression by exogenous testosterone.
AB  - Inhibin has been postulated to be secreted by Sertoli cells in response to
      follicle stimulating hormone (FSH) and in turn to exert an inhibitory effect on
      FSH production. We have investigated this relationship using an assay specific
      for dimeric inhibin B. A total of 56 normal men received 200 mg testosterone
      enanthate (TE) i.m. weekly, for 65 +/- 1 weeks in a trial of hormonal male
      contraception. Before treatment a significant negative correlation between
      inhibin B and FSH concentration (r = 0.49, P < 0.001) was observed. During TE
      treatment, luteinizing hormone (LH) and FSH were rapidly suppressed. This was
      followed by a parallel decline in inhibin B and sperm concentration. During the
      early recovery phase, inhibin B concentrations remained suppressed in men who
      showed a delay in resumption of spermatogenesis, despite higher FSH
      concentrations. Inhibin B returned to pretreatment concentrations after 24 weeks
      recovery, when the inverse relationship with FSH was restored. Our results showed
      the expected inverse physiological relationship between inhibin B and FSH in
      normal men, with a decline during TE treatment and alpha subsequent resumption of
      the inverse relationship during recovery. These data clearly support the
      hypothesis that inhibin B plays a physiological role in the feedback control of
      FSH secretion, and reflects FSH-stimulated Sertoli cell function.

PMID- 9159437
TI  - Intracytoplasmic sperm injection (ICSI) and chromosomally abnormal spermatozoa.
AB  - An infertile couple was referred for intracytoplasmic sperm injection (ICSI)
      because of primary infertility and oligoasthenoteratozoospermia (OAT) in the
      male. It was observed that although the sperm cells presented with an unusual
      head size and multiple tails they were able to fertilize the oocytes after ICSI.
      Subsequent molecular cytogenetic analysis demonstrated de-novo chromosome
      abnormalities in virtually all sperm cells with 40% diploidy and 24% triploidy in
      addition to aneuploidy for the sex chromosomes.

PMID- 9159438
TI  - Testicular cancer and spermatogenesis.
AB  - We retrospectively analysed the characteristics of 54 men with testicular cancer.
      The group comprised 32 men with pure seminoma and 22 with non-seminoma germ cell
      tumours (NSGCT). This group was further compared to 190 healthy sperm donor
      candidates. Sperm quality was found to be higher in the seminoma versus the NSGCT
      patients in: sperm concentration [50 (0-230) versus 17 (0-288) x 10(6)/ml, P <
      0.001], total motile sperm counts (TMC) [57 (0-508) versus 12 (0-854) x
      10(6)/ejaculate, P = 0.002], post-thaw forward motile concentration [3 (0-28)
      versus 1.7 (0-17) x 10(6)/ml, P = 0.003] and motility percentage [20 (0-57)
      versus 12.5 (0-42) %, P = 0.002]. Serum hormone concentrations did not differ
      between these two sub-groups, although the follicle stimulating hormone
      concentrations were higher than normal in both (14.6 +/- 2.5 versus 10.4 +/- 1.4
      mIU/ml, P > 0.05). As is well documented, cancer patients were found to have
      lower sperm quality compared to healthy candidates. The existence of these
      differences, and the fact that testicular cancer affects spermatogenesis,
      indicated that the mechanisms involved in the deterioration of sperm quality can,
      at least partially, be attributed to the type and origin of the malignant cancer.
      The higher sperm counts in the seminoma group may be related to the fact that the
      resemblance of the seminoma cells to normal germ cells is greater than that of
      the NSGCT cells, and therefore they retain a better capacity to function. Due to
      modern assisted reproductive technologies and micromanipulation achievements, the
      lower yield of spermatozoa in severe cases is no longer a major obstacle to
      offering cryopreservation to these patients.

PMID- 9159439
TI  - Assessment of the need for follicle stimulating hormone in early preantral mouse
      follicle culture in vitro.
AB  - In two consecutive controlled experiments 160 early preantral follicles were
      cultured in order to evaluate effects of recombinant follicle stimulating hormone
      (r-FSH) on survival, differentiation, oestradiol and inhibin secretion, cumulus
      mucification and cumulus-corona-oocyte detachment by human chorionic
      gonadotrophin (HCG) stimulation. Nuclear maturation in oocytes was also assessed
      following addition of HCG. A histological analysis of cultured follicles was
      carried out on semi-thin sections at various culture stages. Addition of r-FSH
      was essential for follicle survival for 16 days: without r-FSH only 11% of the
      follicles survived for 12 days (with r-FSH: 79%) and none of these mucified after
      the HCG stimulus. r-FSH promoted granulosa cell proliferation and antral-like
      cavity formation. Without r-FSH, histology of the cultures demonstrated
      degeneration and reduced granulosa cell proliferation; oestradiol and inhibin
      production were reduced. This study illustrates the essential role of FSH in
      promoting the in-vitro growth of early preantral mouse ovarian follicles and in
      maintaining the oocyte under meiotic arrest.

PMID- 9159440
TI  - Specific gonadotrophin-releasing hormone analogue binding predominantly in human
      luteinized follicular aspirates and not in human pre-ovulatory follicles.
AB  - In an attempt to resolve the apparent controversy in the observed effects of
      gonadotrophin-releasing hormone (GnRH) analogues on the ovary, conventional
      binding studies were conducted with a GnRH agonist and an antagonist in various
      ovarian tissues to demonstrate possible GnRH receptor binding. In human
      luteinized granulosa cells derived from unstimulated in-vitro fertilization
      cycles, high affinity receptor binding was present in 17 out of 24 patients,
      while binding was not observed in any of the six pre-ovulatory follicles removed
      during abdominal surgery. Apparently contradictory observations on the direct
      ovarian effects of GnRH analogues may be the result of the intermittent presence
      of high affinity GnRH receptors. Our observations indicate that in the human,
      high affinity ovarian GnRH receptors are present predominantly in ovarian tissue
      after the luteinizing hormone surge. We also propose the possibility of
      regulation and activation of a human follicular GnRH receptor in the ovary as a
      physiological process which may be influenced pharmacologically.

PMID- 9159441
TI  - In-vitro modulation of plasminogen activator activity, prostaglandin E and nitric
      oxide production by interleukin-1 in pregnant mare serum gonadotrophin-primed
      theca-interstitial cells.
AB  - To examine the participation of the theca-interstitial (TI) compartment in
      cytokine modulation of ovarian function, the effects of interleukin-1beta (IL-1)
      on plasminogen activator (PA) activity and on prostaglandin E (PGE) and nitric
      oxide (NO) production were examined in cultures of pregnant mare serum
      gonadotrophin (PMSG)-primed rat TI cells. Exposure to IL-1 (10 ng/ml) resulted in
      a 25% reduction (P < 0.001) in PA activity, concurrent with a 4.6-fold increase
      in the ability of the corresponding conditioned media to inhibit exogenous
      urokinase activity. IL-1 also produced a 4.7-fold increase in PGE content and a
      2.8-fold increase in NO generation. These effects of IL-1 were abolished by the
      IL-1 receptor antagonist, suggesting specific IL-1 receptor-mediated effects.
      Transforming growth factor (TGF)-beta1 (10 ng/ml) significantly attenuated the IL
      1-stimulated PGE production and NO generation but did not affect the ability of
      IL-1 to suppress PA activity and stimulate urokinase inhibitor production. The NO
      synthase inhibitor N-nitro-L-arginine attenuated the IL-1-induced NO generation
      but had no effect on PA activity or PGE production. Thus, NO is not an obligatory
      mediator of IL-1 effects on plasminogen activation and PGE generation in rat
      ovary. The present observations attest to a pleiotropic response of PMSG-primed
      TI cells to IL-1, and suggest a paracrine/autocrine function for the TI
      compartment in ovulation and corpus luteum formation.

PMID- 9159443
TI  - Optimization of a method for deactivation of platelet-activating
      factor:acetylhydrolase in serum for use in in-vitro fertilization culture media.
AB  - Embryos produced by in-vitro fertilization (IVF) may produce less platelet
      activating factor (PAF) than is optimal for development. It was previously shown
      that supplementation of culture media with PAF results in a significant increase
      in pregnancy rate. Human embryos are often cultured in media supplemented with
      serum containing the enzyme PAF:acetylhydrolase (PAF:AH; EC 3.1.1.47), which
      hydrolyses PAF to its inactive form, lyso-PAF. Thus, effective supplementation of
      media with PAF requires inactivation of this enzyme. In this study we examine the
      efficacy of the methods of PAF:AH deactivation used for PAF supplementation of
      IVF culture medium. When the effectiveness of a commonly used acid treatment
      protocol (pH 3.0 at room temperature for 5 min) was examined, it was found that
      it was not completely effective for the majority of sera. When synthetic PAF was
      added to 18 serum samples which had been acid treated, five had 90-100% of the
      original PAF remaining after 24 h (showing that the acid treatment was
      effective), eight had from 10-90% of the original PAF remaining after 24 h, and
      five samples had 0-10%. The extent to which PAF:AH was susceptible to
      deactivation was not associated with the activity in the serum prior to
      treatment, the serum oestradiol concentration, or the cause of infertility. The
      period of acidification and the incubation temperature were assessed to develop a
      new acid-treatment protocol (20 min acid treatment at 37 degrees C) which was
      able to deactivate PAF:AH effectively in all sera (53/53) examined. A trial was
      performed to assess the effect of acid treatment of serum for 5 min at room
      temperature compared with the new protocol (20 min at 37 degrees C) on IVF
      outcome, following PAF supplementation of IVF culture medium. Oocyte recovery,
      fertilization and embryo development rates were equivalent for both groups and
      approximately equal numbers of embryos were transferred or cryopreserved.
      Pregnancy rates were not significantly different (14.6 versus 20.0%) for the two
      treatments, with a trend towards a higher pregnancy rate with the new acid
      treatment protocol. The results show that this new procedure for acid treatment
      of serum in combination with PAF supplementation does not have detrimental
      effects on embryos and their pregnancy outcome and is therefore suitable for use
      in IVF.

PMID- 9159442
TI  - Treatment-related chromosome abnormalities in human embryos.
AB  - Mosaicism was studied in good quality embryos from four different centres in
      order to assess the effects of follicular induction and exposure to laboratory
      conditions on chromosomal status. The donated embryos were fully biopsied and
      analysed by fluorescence in-situ hybridization using probes for chromosomes X, Y,
      13, 18 and 21, simultaneously. The number of abnormal cells present indicated the
      division at which mosaicism first occurred (4/4 cells at first division, 2/4
      cells at second, 2/8 at third). The rate of mosaicism in embryos from different
      centres varied greatly (P < 0.001). Most of the mosaic embryos were obtained
      before 1991. In one clinic increased mosaicism was found in embryos obtained
      before 1991 when compared to embryos obtained thereafter. The results suggest
      that certain culture conditions and/or hormonal stimulation protocols may induce
      chromosomal abnormalities and partly explain differences in pregnancy rates
      between in-vitro fertilization centres.

PMID- 9159444
TI  - The influence of sera, follicular fluids and seminal plasma on human sperm-zona
      pellucida binding.
AB  - The purpose of this study was to assess the influence of male, female and fetal
      cord sera, follicular fluid, and seminal plasma on human sperm-zona pellucida
      binding, using the hemizona assay. Steroids, gonadotrophins, growth hormone and
      prolactin concentrations in follicular fluid and sera were also analysed. The
      influence of follicular fluid (10 or 50%, v/v) and sera (10%) on sperm-zona
      pellucida binding was investigated by supplementing the sperm processing medium
      as well as the sperm-hemizona incubation medium. Different seminal plasma
      concentrations (1 or 10%) were added to the sperm-hemizona incubation medium.
      Supplementation with 10% day 3 donor serum was used as a control throughout
      experimentation. Although supplementation with male sera and fetal cord serum
      exerted a stimulatory effect (36 and 90% respectively; P < 0.029) on sperm-zona
      pellucida binding, hemizona indices obtained with addition of male sera, fetal
      cord serum and sera obtained from sub-fertile in-vitro fertilization (IVF)
      patients on day 12 of their menstrual cycle did not differ significantly (P >
      0.05). Final progesterone concentrations in sperm-zona pellucida incubation media
      (10% follicular fluid supplementation), which ranged from 0.788 to 3.85
      microg/ml, enhanced sperm binding to the zonae by >100% (P < 0.02). The
      utilization of follicular fluid (10%) as a natural physiological stimulus to
      enhance sperm-zona pellucida binding in an IVF setting is recommended. The
      presence of seminal plasma in the spermzona pellucida incubation media showed no
      beneficial effect on the binding ability of sperm, and can be viewed as an
      unfavourable substance in the proximity of the oocyte.

PMID- 9159445
TI  - The frequency and developmental capability of human embryos containing
      multinucleated blastomeres.
AB  - The frequency of multinucleated blastomeres (MNB) in 2- and 4-cell stage human
      embryos was recorded immediately before embryo transfer using a high-power
      inverted microscope. About 44% of patients (150/338) possessed embryos exhibiting
      MNB. The appearance of this nuclear abnormality was not correlated with maternal
      age. Overall, 15% of the otherwise good quality embryos (274/1885) that developed
      after monospermic fertilization contained several multinuclei (from two to seven)
      in at least one cell. Quite often MNB were found within all cells of the embryo
      (50% in 2-cell embryos). Blastomere multinucleation was significantly higher in 2
      cell than 4-cell embryos (P <0.0001). This suggests that a considerable number of
      human embryos become abnormal during the first embryonic division. The embryos
      containing MNB were usually excluded for uterine transfers, with the exception of
      19 cases when only such embryos could be replaced (6%; 19/338 patients). The
      results demonstrated that embryos with MNB may implant (4/19 cases; 21%) and they
      can lead to both spontaneous abortions and the successful birth of healthy
      infants (two cases). The fact that in the successful cases, 2-cell stage embryos
      with a mononucleated and a binucleated blastomere were transferred also suggests
      that due to the cell totipotency, development of a healthy baby is possible from
      one normal blastomere. Since multinucleation in early embryos may reflect gross
      chromosomal abnormalities or development of mosaic embryos, it is advisable not
      to replace embryos with MNB. Occasional transfers, however, can be considered
      because defective embryos may sometimes develop normally.

PMID- 9159446
TI  - Intracytoplasmic sperm injection combined with preimplantation genetic diagnosis
      for the prevention of recurrent gestational trophoblastic disease.
AB  - A strategy for the prevention of repeated molar pregnancies by using
      intracytoplasmic sperm injection (ICSI) coupled with preimplantation genetic
      diagnosis (PGD) with fluorescence in-situ hybridization (FISH) was developed. In
      this approach, complete moles which arise from dispermic fertilization are
      avoided by the use of ICSI. ICSI is followed by preimplantation selection against
      the transfer of 46,XX embryos, thus preventing complete moles resulting from a
      fertilization of an inactive oocyte, by a haploid X-bearing spermatozoon which
      subsequently duplicates. Triploid partial moles which arise mainly from dispermic
      fertilization may also be prevented by ICSI. The preimplantation confirmation of
      diploidy by FISH guards against triploid partial moles which may result from
      mechanisms other than dispermic fertilization. The employment of this strategy in
      an attempt to prevent a repeated event of molar pregnancy in a patient with a
      history of two previous episodes of gestational trophoblastic disease is
      reported.

PMID- 9159447
TI  - Triple colour fluorescent in-situ hybridization for chromosomes X,Y and 1 on
      spare human embryos.
AB  - The potential for implantation of human embryos obtained by in-vitro
      fertilization is presumably determined to a large extent by their chromosomal
      constitution but cytogenetic analysis of preimplantation embryos has been
      hampered by a number of practical and technical problems. With the advent of
      fluorescent in-situ hybridization (FISH) a practical method for numerical
      chromosomal analysis has become available. A limited amount of data has been
      obtained with FISH on human embryos using probes binding to chromosomes X, Y, 16,
      18 and 13/21 combined or for chromosomes X and Y or 1 and 17. It was our purpose
      to extend these data by the combined analysis of chromosomes X, Y and 1 in spare
      human embryos. A short fluorescent in-situ hybridization procedure involving the
      simultaneous use of three deoxyribonucleic acid probes detected with red, green,
      and a mixture of red and green was used to determine chromosomal abnormalities in
      116 spare embryos with a poor morphological score and/or displaying one or more
      multinucleated blastomeres. The majority of the embryos was obtained by
      intracytoplasmic sperm injection. Less than half of the embryos (n = 54) were
      diploid and only 39 of them were uniformly XY11 or XX11; two embryos showed a non
      disjunction and 13 embryos were aneuploid. Of the remainder, 22 were mosaic, nine
      were either haploid, triploid or tetraploid and 12 embryos were classified as
      chaotic. The latter pattern was particularly frequent in multinucleated
      blastomeres. Our data are comparable with those obtained with FISH using other
      chromosomal probes and confirm that the majority of preimplantation embryos carry
      a numerical chromosomal defect. Aneuploidy for chromosome 1 does not appear to be
      more common in preimplantation embryos than is reported for other chromosomes.
      Although the high incidence of chromosomal anomalies is presumably biased by the
      fact that only embryos with a poor morphological score were analysed, it
      nevertheless indicates that natural selection is the foremost reason for the low
      implantation rates of human preimplantation embryos in in-vitro fertilization
      (IVF) programmes.

PMID- 9159449
TI  - Comparison of ultrasonographic findings in spontaneous abortions with normal and
      abnormal karyotypes.
AB  - To determine whether ultrasonographic findings can predict the karyotype of
      spontaneous abortions, 137 pregnancies (54 spontaneous, 83 assisted ovulatory
      cycles) that subsequently aborted and had chromosome analysis performed on the
      products of conception were studied ultrasonographically. Transvaginal ultrasound
      was performed using an Acuson 128XP/10 with 7.5 MHz probe. The numbers of empty
      gestational sacs, small and normal for gestational size, embryonic poles and
      embryos with documented cardiac activity were calculated. The frequency of each
      of these findings in pregnancies with normal and abnormal karyotypes was
      compared. Of the 137 spontaneous abortions, 51 had normal chromosome analyses and
      86 had abnormal karyotypes (68 aneuploidies and 18 polyploidies).
      Ultrasonographic findings in the 51 karyotypically normal pregnancies included 16
      (31%) with empty gestational sacs, and 35 (69%) with embryonic poles, of which 24
      (69%) were at least 1 week smaller than expected for gestational age and 11 (31%)
      were the expected size. Embryonic cardiac activity was documented in 22 (63%) of
      the 35 embryonic poles. Amongst 86 pregnancies with abnormal karyotypes, similar
      frequencies of ultrasound findings were found: 23 (27%) with empty gestational
      sacs, 42 (67%) with embryonic poles smaller than expected for gestational age,
      and 50 (79%) embryos lost after documentation of embryonic cardiac activity. No
      differences in the frequency of ultrasonographic findings of empty gestational
      sacs, small embryonic pole and embryonic cardiac activity were observed between
      karyotypically normal and abnormal spontaneous abortions. Ultrasonographic
      findings cannot predict the karyotype of spontaneous abortions.

PMID- 9159448
TI  - Distribution of the A and B forms of the progesterone receptor messenger
      ribonucleic acid and protein in uterine leiomyomata and adjacent myometrium.
AB  - The two forms of the progesterone receptor, PR-A and PR-B, are independently
      regulated at the transcriptional level, and show distinct responses to
      progesterone antagonists. We were interested in possible differences in the PR-A
      to PR-B ratio between uterine myometrium and leiomyomata (fibroid), that might
      influence the response of fibroids to progesterone agonists and antagonists, and
      thus have consequences for the treatment of this condition. Fibroid and adjacent
      normal myometrium were obtained from 11 women undergoing hysterectomy.
      Immunohistochemistry using a monoclonal antibody which recognizes both PR-A and
      PR-B showed exclusively nuclear staining, and this was stronger in the
      leiomyomata than in adjacent myometrium. An antibody specific for PR-B gave
      fainter staining of both tissues. Western blotting confirmed a higher
      concentration of PR in leiomyomata than myometrium in eight out of 11 cases. In
      all cases both forms were present, with a consistent dominance of PR-A over PR-B.
      However an RNase protection assay showed that there was no difference between the
      concentrations of mRNA encoding PR-A and PR-B, or between the mRNA concentrations
      in leiomyomata and normal myometrium. We conclude that the observed differences
      between the levels of immunoreactive PR in leiomyomata and myometrium may result
      from post-translational control, and support the use of progesterone antagonists
      in the treatment of leiomyomata.

PMID- 9159450
TI  - Age of the uterus does not affect pregnancy or implantation rates; a study of egg
      donation in women of different ages sharing oocytes from the same donor.
AB  - The importance of age of the recipient (uterine age) with regards to pregnancy
      rate, delivery rate and miscarriage rate following oocyte donation was evaluated
      using retrospective data analysis of cases where two recipients from different
      age groups shared oocytes from a single donor and had equal numbers of embryos
      transferred. A total of 104 women (21-52 years of age) underwent a total of 104
      cycles of oocyte donation. They were divided into groups according to age (group
      A: age 39 years or less and group B: age between 40 and 52 years). The minimum
      age difference between a pair of recipients was five years. Hormone replacement
      therapy (HRT) was given using oestradiol valerate (6 mg daily) for at least 10
      days, followed by a combination of oestradiol with either intramuscular
      progesterone (100 mg daily), or vaginally administered micronized progesterone
      (300 microg daily). Women with ovarian function received down-regulation using a
      luteinizing hormone-releasing hormone (LHRH) analogue before hormone replacement
      was commenced. A total of 52 transfer cycles was performed in each age group and
      pregnancy, delivery and miscarriage rates were analysed as outcome measures; 20
      pregnancies were achieved in each group (an identical pregnancy rate of 38.5%).
      In group A seven pregnancies miscarried out of 20 (35%), which was not
      significantly different from the rate in the older population, group B, where
      eight out of 20 pregnancies miscarried (40%). The delivery rate in group A was
      25% (13 out of 52), again not significantly different from the delivery rate in
      group B of 23.1% (12 out of 52). In conclusion, using egg donation as a model,
      the decline in fecundity with age cannot be explained by uterine factors alone.

PMID- 9159451
TI  - The effects of growth factors on human normal placental cytotrophoblast cell
      proliferation.
AB  - The effects of growth factors were investigated on the proliferation of a normal
      placental cytotrophoblast cell line (NPC). Epidermal growth factor (EGF),
      transforming growth factor alpha (TGF alpha) and insulin-like growth factor-I
      (IGF-I) stimulated NPC cell proliferation. In contrast, TGFbeta1 was found to be
      a negative regulator, inhibiting EGF-induced cell proliferation. When EGF/TGF
      alpha receptor was analysed by radio-ligand binding, two binding sites of
      different affinities were revealed in the proliferating NPC cells but only the
      low affinity binding site was detected in the non-proliferating cytotrophoblast
      cells in primary cultures. The results suggest that EGF stimulates
      cytotrophoblast proliferation through high affinity binding sites.

PMID- 9159452
TI  - Cumulative conception and live birth rates after oocyte donation: implications
      regarding endometrial receptivity.
AB  - The purpose of the present study was to determine the cumulative likelihood of
      pregnancy success after repetitive cycles of oocyte donation and specifically to
      examine the influence of recipient age and diagnosis upon the cumulative
      likelihood of pregnancy in an effort to identify any potential subgroup of
      recipients who might have diminished endometrial receptivity. We retrospectively
      analysed the outcome of 418 consecutive embryo transfer cycles among 276
      recipients of oocyte donation in our institution. We analysed clinical pregnancy
      and delivery rates in the recipients divided by age groups and diagnostic groups.
      For the purpose of life-table analysis, only cycles prior to and including the
      first cycle producing a successful pregnancy were included. Frozen-thawed embryo
      transfers were not included in the analysis. The overall clinical pregnancy rate
      was 36.2% (95% CI 31-41%) and the cumulative pregnancy rate after four cycles was
      87.9%. The overall delivery rate was 29.3% (95% CI 25-33%) and the cumulative
      delivery rate after four cycles was 86.1%. There were no statistically
      significant differences in any of the rates attributable to recipient age or
      diagnosis. No decline in per cycle success was noted over consecutive cycles. We
      conclude that neither recipient age nor diagnosis plays a substantial role in the
      success of oocyte donation, implying that endometrial receptivity is unaltered by
      age or diagnosis. Furthermore, up to four successive cycles of oocyte donation
      are associated with the same probability of success.

PMID- 9159453
TI  - Insulin-like growth factor I in fetal serum obtained by cordocentesis is
      correlated with intrauterine growth retardation.
AB  - We examined whether insulin-like growth factor-I (IGF-I) and one of its binding
      proteins (IGFBP-1) in fetal serum obtained by cordocentesis is correlated with
      intrauterine growth retardation (IUGR) and weight estimation by ultrasound.
      Cordocentesis sera from 27 fetuses suspected of having IUGR were analysed for IGF
      I and IGFBP-1 by radioimmunoassay. The results showed that IGF-I concentrations
      were correlated significantly with birth weight (P < 0.001) and placenta weight
      (P < 0.05). Mean fetal concentrations of IGF-I were 38 +/- 18 microg/l. In
      patients (n = 11) with a weight deviation at delivery <-33%, IGF-I concentrations
      were 24.1 +/- 13.2 microg/l. IGFBP-1 was inversely correlated with birth weight
      (P < 0.006) and concentrations of IGF-I. Mean plasma concentrations of IGFBP-1
      were 234.2 +/- 161.4 microg/l. Furthermore, IGF-I concentrations were correlated
      with the weight deviation estimated by ultrasonography at the time of
      cordocentesis (P < 0.007), as well as with the weight deviation at delivery (P <
      0.0001). The actual weight deviation at delivery was correlated more strongly
      with fetal IGF-I concentrations than with the estimated weight deviation at
      cordocentesis. The lowest concentrations of IGF-I were found in patients with a
      weight deviation <-33%. Very low concentrations of IGF-I are thus associated with
      IUGR, indicating that IGF-I measured in fetal serum may increase the predictive
      value of ultrasonographic weight estimation.

PMID- 9159454
TI  - Feto-maternal bleeding following coelocentesis.
AB  - The potential risk of feto-maternal haemorrhage following coelocentesis was
      examined in 17 singleton pregnancies at 6-11 weeks of gestation by measuring
      maternal serum concentration of alpha fetoprotein (AFP) before and 1 and 10 min
      after the procedure. There was no significant difference between the maternal
      serum AFP concentration before coelocentesis (median 7.5, range 4.5-21.5 IU)
      compared to the values at 1 min (median 8.6, range 3.9-17.8; Z = -0.504, P =
      0.614), and 10 min (median 7.5, range 5.7-20.6; Z = -0.432, P = 0.666) after the
      procedure. These findings demonstrate that coelocentesis is not associated with
      significant feto-maternal haemorrhage.

PMID- 9159455
TI  - Isolation of macrophages (Hofbauer cells) from human term placenta and their
      prostaglandin E2 and thromboxane production.
AB  - Placental macrophages (Hofbauer cells) are located close to trophoblast cells and
      fetal capillaries, which makes them ideal candidates for involvement in
      regulatory processes within the villous core. Their production of various
      cytokines and prostaglandin (PG) synthesizing enzymes has previously been shown
      immunohistochemically. Hofbauer cells were isolated from human placenta after
      term deliveries by Ficoll and Percoll gradient centrifugation. Remaining
      trophoblast cells were removed with anti-epidermal growth factor (EGF)-receptor
      coated Dynabeads followed by differential adherence. The identity of isolated
      cells was investigated by immunohistochemistry with anti-CD68, which showed that
      >90% cells were positive. After a 36 h recovery period in either 20% O2 or 5% O2,
      fresh medium was applied and PGE2 and thromboxane (TXA2) production analysed by
      enzyme immunoassay at 4, 8, and 24 h. PGE2 and TXA2 were both produced by
      placental macrophages with PGE2 synthesis being predominant. Concentrations of
      both could be stimulated by lipopolysaccharide with maximum effect after 24 h.
      Culture in low oxygen caused decreased PGE2 concentrations, whereas TXA2
      production remained unchanged. In conclusion, the presented isolation protocol
      allows further study of Hofbauer cell function. This study also presents novel
      findings regarding the prostaglandin production of term Hofbauer cells under
      normal and hypoxic conditions.

PMID- 9159456
TI  - Molar pregnancy and living normal fetus coexisting until term: prenatal
      biochemical and sonographic diagnosis.
AB  - The extremely rare condition of molar pregnancy with a coexisting fetus
      progressing to a viable infant, is reported. At 20 weeks gestational age,
      prenatal diagnosis was made by biochemical and sonographic findings, in which
      elevated free beta-human chorionic gonadotrophin (HCG, 500 ng/ml) was noted and
      ultrasound showed a well-defined multicystic snowstorm-like mass connecting with
      placenta. Chromosomal evaluation by amniocentesis was normal (46,XY) and
      ultrasound showed no fetal abnormalities, so the patient decided to keep the
      pregnancy and had no significant complications noted in the antepartal period. At
      38 weeks gestational age, a Caesarean section was performed due to cephalopelvic
      disproportion and a 3380 g, living boy was delivered. The infant did not show any
      abnormality. The placenta and the connecting hydatidiform molar tissue were
      delivered manually. Subsequently, since persistent elevated beta-HCG was noted 2
      months later, the patient was treated with chemotherapy for gestational
      trophoblastic disease. A normal beta-HCG concentration was noted thereafter.
      Prenatal differential diagnosis and postnatal management are discussed as well as
      the rationale for allowing the pregnancy to continue after the diagnosis at 20
      weeks gestational age.

PMID- 9159457
TI  - Pregnancy after transfer of embryos which were generated from in-vitro matured
      oocytes.
AB  - In-vitro maturation of human oocytes is an important technique in assisted
      reproduction due to its potential for reducing the use of fertility drugs. We
      offered this technique as an alternative to cancelling the cycle to a patient who
      was at risk of ovarian hyperstimulation syndrome (OHSS) after treatment with
      gonadotrophin-releasing hormone analogue (GnRHa) and human menopausal
      gonadotrophin (HMG). The patient had 40 visible antral follicles with a maximum
      diameter of 13 mm and an oestradiol concentration of 14,000 pmol/l on cycle day
      12. Immature oocytes were aspirated transvaginally under ultrasound guidance. Ten
      cumulus-enclosed oocytes were harvested and nine of them completed nuclear
      maturation to metaphase II after 48 h in culture. By 18 h after an
      intracytoplasmic sperm injection (ICSI) procedure, seven of these metaphase II
      stage oocytes displayed two distinct pronuclei and two polar bodies. All
      fertilized oocytes but one underwent cleaveage; four of these were transferred 2
      days later. Endometrial priming was initiated with 8 mg oestradiol valerate daily
      from the day of oocyte retrieval and 50 mg progesterone was injected i.m. daily
      starting 2 days after that. A single intrauterine sac was seen containing one
      fetus with positive fetal heart beat on ultrasound at 7 weeks of gestation.
      Unfortunately, the pregnancy ended at 24 weeks shortly after premature rupture of
      membranes; a live healthy-looking girl was delivered who died 18 days later.

PMID- 9159458
TI  - Conservative treatment of cervical pregnancy by curettage and local prostaglandin
      injection.
AB  - Recently, various conservative regimens for the treatment of cervical pregnancy
      have been introduced to preserve fertility in young women, with methotrexate
      being one of the most widely used drugs. The success of conservative treatment
      depends on early preoperative diagnosis. We report three cases of first trimester
      cervical pregnancy, successfully treated by curettage to evacuate the conceptus,
      followed by local prostaglandin instillation to prevent severe haemorrhage. In
      one patient, intra-amniotic instillation of hyperosmolar glucose was necessary to
      terminate fetal cardiac activity. beta-Human chorionic gonadotrophin returned to
      normal within 3 weeks in one patient and within 7 weeks in another, both of whom
      became pregnant again within 1 year, resulting in term deliveries. The third
      patient was lost to follow-up after 1 week. The advantage of prostaglandin and
      curettage is the absence of major side-effects to the mother or the fetus of a
      subsequent pregnancy. The management strategies used in the treatment of cervical
      pregnancies and the results obtained since the introduction of methotrexate in
      1989 are discussed in the context of previously published literature. The
      incidence of subsequent pregnancies among women treated medically versus women
      treated surgically is reported.

PMID- 9159459
TI  - ESHRE guidelines for training, accreditation and monitoring in gynaecological
      endoscopy. European Society for Human Reproduction and Embryology. Committee of
      Special Interest Group on Reproductive Surgery.

PMID- 9159460
TI  - LH/FSH ratio as a predictor of ovarian hyperstimulation syndrome.

PMID- 9159461
TI  - Preimplantation diagnosis in older patients.

PMID- 9159462
TI  - Preimplantation diagnosis in older patients.

PMID- 9159463
TI  - Consensus workshop on advanced diagnostic andrology techniques.

PMID- 9159464
TI  - Consensus workshop on advanced diagnostic andrology techniques. ESHRE Andrology
      Special Interest Group.

PMID- 9159465
TI  - RNA polymerase I transcription termination: similar mechanisms are employed by
      yeast and mammals.
AB  - Termination of RNA polymerase I (Pol I) transcription requires the interaction of
      a specific DNA binding factor with terminator elements downstream of the pre-rRNA
      coding region. Both the terminator elements and the respective termination
      factors are distinct in yeast and mammals, and differences in the mechanism of
      transcription termination have been postulated. We have compared in vitro
      transcription termination of yeast and mouse Pol I using both the murine factor
      TTF-I, and the yeast homolog Reb1p. We show that, similar to TTF-I, Reb1p was
      sufficient for pausing of Pol I from either species, but was unable to cause
      release of the nascent transcripts from the paused ternary complex. The
      deficiency of Reb1p to mediate transcript release from Pol I of either species
      was complemented by the recently characterized murine release factor. Thus, both
      yeast and mouse Pol I termination requires a trans-acting factor that, in
      conjunction with the T-rich flanking sequence, releases the transcripts and Pol I
      from the template. The observation that the murine factor causes dissociation of
      ternary transcription complexes arrested by Reb1p suggests that the mechanism of
      Pol I termination is highly conserved from yeast to mammals.

PMID- 9159466
TI  - Processing of the Bacillus subtilis thrS leader mRNA is RNase E-dependent in
      Escherichia coli.
AB  - We have recently reported that processing occurs in the untranslated leader
      region of several members of a family of Gram-positive genes regulated by tRNA
      mediated antitermination. We showed that cleavage at this site plays an important
      role in the induction of Bacillus subtilis thrS gene expression, following
      threonine starvation, by stabilising the downstream mRNA. Here we show that, when
      transferred on a plasmid, processing of the B. subtilis thrS leader can occur at
      the same site in Escherichia coli. Cleavage at this site is dependent on the E.
      coli endoribonuclease E, both in vivo and in vitro, suggesting that a functional
      homologue of RNase E is responsible for thrS processing in B. subtilis.

PMID- 9159467
TI  - A RNA polymerase III-based two-hybrid system to study RNA polymerase II
      transcriptional regulators.
AB  - In a previous study, we explored the mechanisms of SNR6 gene activation by
      grafting a heterologous DNA-binding domain, GAL4-(1-147), to various components
      of the yeast RNA polymerase III transcription system. Here, we demonstrate that a
      modified SNR6 gene harboring GAL4-binding sites (UAS(G)-SNR6) can be efficiently
      activated via an intervening, unrelated protein-protein interaction, thus laying
      the foundations of a RNA polymerase III-based two-hybrid system. In a model
      system, the interacting proteins recruiting TFIIIC to DNA were PRP21 and PRP9 or
      PRP21 and PRP11. Mutations affecting the interaction between PRP21 and PRP9, or
      PRP21 and PRP11 decreased UAS(G)-SNR6 activation level proportionally. RNA
      polymerase II transcriptional activators, like GAL4, VP16 or p53, fused to GAL4
      DNA-binding domain, did not activate the UAS(G)-SNR6 gene. However, GAL4 strongly
      activated UAS(G)-SNR6 when GAL80, an interacting protein, was fused to TFIIIC.
      This result indicates that this two-hybrid system can be used to assess the
      interactions between RNA polymerase II regulatory proteins and their partners.

PMID- 9159468
TI  - Possible roles of HIV-1 nucleocapsid protein in the specificity of proviral DNA
      synthesis and in its variability.
AB  - Retroviral nucleocapsid (NC) protein is an integral part of the virion
      nucleocapsid where it coats the dimeric RNA genome. Due to its nucleic acid
      binding and annealing activities, NC protein directs the annealing of the tRNA
      primer to the primer binding site and greatly facilitates minus strand DNA
      elongation and transfer while protecting the nucleic acids against nuclease
      degradation. To understand the role of NCp7 in viral DNA synthesis, we examined
      the influence of NCp7 on self-primed versus primer-specific reverse
      transcription. The results show that HIV-1 NCp7 can extensively inhibit self
      primed reverse transcription of viral and cellular RNAs while promoting primer
      specific synthesis of proviral DNA. The role of NCp7 vis-a-vis the presence of
      mutations in the viral DNA during minus strand elongation was examined. NCp7
      maximized the annealing between a cDNA(-) primer containing one to five
      consecutive errors and an RNA representing the 3' end of the genome. The ability
      of reverse transcriptase (RT) in the presence of NCp7 to subsequently extend the
      mutated primers depended upon the position of the mismatch within the
      primer:template complex. When the mutations were at the polymerisation site,
      primer extension by RT in the presence of NCp7 was very high, about 40% for one
      mismatch and 3% for five consecutive mismatches. Mutations within the DNA primer
      or at its 5' end had little effect on the extension of viral DNA by RT. Taken
      together these results indicate that NCp7 plays major roles in proviral DNA
      synthesis within the virion core due to its ability to promote prime-specific
      proviral DNA synthesis while concurrently inhibiting non-specific reverse
      transcription of viral and cellular RNAs. Moreover, the observation that NCp7
      enhances the incorporation of mutations during minus strand DNA elongation
      favours the notion that NCp7 is a factor contributing to the high mutation rate
      of HIV-1.

PMID- 9159469
TI  - Analysis of the in vivo decay of the Escherichia coli dicistronic pyrF-orfF
      transcript: evidence for multiple degradation pathways.
AB  - Messenger RNA decay in Escherichia coli is slowed in pnp-7 (PNPase) rnb-500
      (RNase II) rne-1(RNase E) multiple mutants. We have used Northern blots, S1
      nuclease protection and primer extension analysis to map 18 endonucleolytic
      cleavage sites within the pyrF-orfF dicistronic transcript. Although examination
      of a total of 27 cleavage sites including those determined for the monocistronic
      trxA transcript revealed a complex pattern, the central four nucleotides within a
      cluster of 12 residues encompassing the cleavage sites showed a definite A/U
      preference. Also of interest was the processing of the dicistronic transcript to
      remove the downstream orfF sequence as a stable but untranslated RNA fragment.
      The data provide further support for the hypothesis that multiple decay pathways
      are involved in the decay of a single transcript. In particular, the pyrF-orfF
      transcript apparently can be degraded either in the 5' to 3' or the 3' to 5'
      direction. Our results are discussed in light of current models of mRNA decay
      involving polyadenylation and multiprotein decay complexes.

PMID- 9159470
TI  - Analysis of the tobacco chloroplast DNA replication origin (oriB) downstream of
      the 23 S rRNA gene.
AB  - We have mapped the origin of DNA replication (oriB) downstream of the 23 S rRNA
      gene in each copy of the inverted repeat (IR) of tobacco chloroplast DNA between
      positions 130,502 and 131,924 (IR(A)) by a combination of approaches. In vivo
      chloroplast DNA replication intermediates were examined by two-dimensional
      agarose gel electrophoresis. Extended arc patterns suggestive of replication
      intermediates containing extended single-stranded regions were observed with the
      4.29 kb SspI fragment and an overlapping EcoRI fragment from one end of the
      inverted repeat, while only simple Y patterns were observed with a 3.92 kb BamHI
      KpnI fragment internal to the SspI fragment. Other restriction fragments of
      tobacco chloroplast DNA besides those at the oriA region also generated only
      simple Y patterns in two-dimensional agarose gels. Several chloroplast DNA clones
      from this region were tested for their ability to support in vitro DNA
      replication using a partially purified chloroplast protein fraction. Templates
      with a deletion of 154 bp from the SspI to the BamHI sites near the end of the
      inverted repeat resulted in a considerable loss of in vitro DNA replication
      activity. These results support the presence of a replication origin at the end
      of the inverted repeat. The 5' end of nascent DNA from the replication
      displacement loop was identified at position 130,697 for IR(A) (111,832 for
      IR(B)) by primer extension. A single major product insensitive to alkali and
      RNase treatment was observed and mapped to the base of a stem-loop structure
      which contains one of two neighboring BamHI sites near the end of each inverted
      repeat. This provides the first precise determination of the start site of DNA
      synthesis from oriB. Adjacent DNA fragments containing the stem-loop structure
      and the 5' region exhibit sequence-specific gel mobility shift activity when
      incubated with the replication protein fraction, suggesting the presence of
      multiple binding sites.

PMID- 9159471
TI  - Biochemical and mutational studies of the 5'-3' exonuclease of DNA polymerase I
      of Escherichia coli.
AB  - In order to improve our understanding of the 5'-3' exonuclease reaction catalyzed
      by Escherichia coli DNA polymerase I, we have constructed expression plasmids and
      developed purification methods for whole DNA polymerase I and its 5'-3'
      exonuclease domain that allow the production of large quantities of highly
      purified material suitable for biophysical and other studies. We have studied the
      enzymatic properties of the 5'-3' exonuclease, both as an isolated domain and in
      the context of the whole polymerase, using a variety of model oligonucleotides to
      explore the enzyme-substrate interaction. The 5'-3' exonuclease is known to be a
      structure-specific nuclease that cleaves a 5' displaced strand at the junction
      between single-stranded and duplex regions. Since the isolated domain shows the
      same structure specificity as the whole polymerase, the correct geometry of
      substrate binding is achieved without the assistance of the polymerase domain.
      The 5'-3' exonuclease reaction has a strict requirement for a free 5' end on the
      displaced strand; however, the upstream template and primer strands are
      dispensable. Site-directed mutagenesis of the ten carboxylate residues that are
      highly conserved among bacterial and bacteriophage 5'-3' exonucleases indicates
      that nine of them are important in the reaction. This finding is discussed in
      relation to structural and mutational data for related 5' nucleases.

PMID- 9159472
TI  - Complete transcriptional map of yeast chromosome XI in different life conditions.
AB  - Systematic sequencing of the genome of Saccharomyces cerevisiae has demonstrated
      the existence of many novel genes, whose functions need to be studied. Entire
      chromosome sequences also offer the possibility to examine functional properties
      of the genome at a higher hierarchical level than the genes themselves. We used
      ordered DNA fragments of chromosome XI to systematically probe yeast DNA and
      total RNA extracted from MAT a, MAT alpha and diploid cells grown under three
      different conditions. Taking into account transcript sizes and uniqueness of
      probes, we attributed 94 transcripts to sequence-predicted open reading frames
      (ORFs) or tRNA genes; another 83 being tentatively assigned. The remaining 187
      ORFs on chromosome XI do not correspond to transcripts detected under our
      conditions. More than 80% of transcripts are constitutively expressed, others are
      regulated by medium composition or cell type, the most frequent regulations being
      determined by carbon source (glycerol/glucose) or rich versus synthetic medium.
      Moreover, we show that transcript levels and regulation patterns are not
      statistically different between ORFs of unknown function, which constitute ca.
      40% of the total, and previously identified genes (ca. 30%) or their structural
      homologues.

PMID- 9159473
TI  - Transfer RNA gene redundancy and translational selection in Saccharomyces
      cerevisiae.
AB  - A total of 274 transfer RNA genes, representing the entire tRNA gene set of the
      yeast Saccharomyces cerevisiae, has been extracted from the whole genome sequence
      of this organism using a dedicated search algorithm (Pol3scan). All tRNA genes
      were assigned to 42 classes of distinct codon specificity. Accordingly, four
      deviations from previously proposed rules for third position wobble pairing in
      yeast, three G:U and one A:I codon-anticodon pairings, were found to be required
      to account for the reading of 61 coding triplets. The gene copy number for
      individual tRNA species, which ranges from one to 16, correlates well with both
      the frequency of codon occurrence in a sample of 1756 distinct protein coding
      sequences (r = 0.82) and the previously measured intracellular content of 21 tRNA
      species. A close link between tRNA gene redundancy and the overall amino acid
      composition of yeast proteins was also observed. Regression analysis values for
      individual protein coding sequences proved to be effective descriptions of the
      translational selective pressure operating on a particular gene. A significantly
      stronger co-adaptation between codon choice and tRNA gene copy number was
      observed in highly expressed genes. These observations strongly support the
      notion that intracellular tRNA levels in normally growing yeast cells are mainly
      determined by gene copy number, which, along with codon choice, is the key
      parameter acted upon by translational selection.

PMID- 9159474
TI  - Solution structure as a function of pH of two central mismatches, C . T and C .
      C, in the 29 to 39 K-ras gene sequence, by nuclear magnetic resonance and
      molecular dynamics.
AB  - The DNA duplexes 5' d(GCCACCAGCTC) x d(GAGCTXGTGGC), where the base X is either
      cytosine or thymine, have been studied by one and two-dimensional nuclear
      magnetic resonance, energy minimization and molecular dynamics. The sequence
      studied corresponds to the region 29 to 39 of the K-ras gene and is a hot spot
      for mutations. The results show that both duplexes adopt a globally B-DNA-type
      structure. For the C x C mismatch, we observe a structural change as a function
      of pH with an apparent pK of 6.95. The neutral species has only one hydrogen bond
      between the two bases but shows two families of wobble structures where one base
      or the other is displaced in the major groove. The protonated species has two
      hydrogen bonds and two structures but of unequal populations. In both systems,
      the sugar puckers remain predominantly C2'-endo and no significant changes in the
      backbone structure are observed. The neutral C . T mismatch is stabilized by two
      hydrogen bonds but, surprisingly, it can also be protonated, although the
      apparent pK is much lower, 5.65. In this case, protonation does not result in an
      additional hydrogen bond but must be due to better base-stacking interactions for
      C+ x T. The NMR data show that the environment of the T imino proton is very
      similar for C x T and C+ x T, although the hydrogen bond acceptor would be
      expected to be a nitrogen atom in the former case and an oxygen atom in the
      latter. We propose that for both structures there is an intervening water
      molecule which in addition reduces backbone strain. We have also measured the
      fluctuations during molecular dynamics runs in these mismatches. All are greater
      than for Watson-Crick base-pairs and the C x C mismatch shows very pronounced
      mobility.

PMID- 9159475
TI  - Solution structure of the conserved 16 S-like ribosomal RNA UGAA tetraloop.
AB  - The solution structure of the highly conserved UGAA tetraloop found at the 3' end
      of eukaryotic 16 S-like ribosomal RNA has been solved by nuclear magnetic
      resonance spectroscopy in the form of the 12 nucleotide hairpin 5'
      GGUG[UGAA]CACC. The UGAA tetraloop displays a novel fold. The backbone turn
      occurs between the G and the third A in the loop, with the U and G in a 5' stack
      and the As in a 3' stacking arrangement. The loop is closed by a U-A mismatch in
      which the O2, 2'OH, and O4' groups of the U are within hydrogen bonding distance
      of the amino group of the A. The tetraloop does not make a uridine-turn, even
      though its sequence is identical to a U-turn found within the anticodon loop of
      tRNA(Phe). The hydrogen bonding pattern in the tetraloop provides insight into
      the function of base modifications found in vivo within this portion of 16 S-like
      rRNA.

PMID- 9159476
TI  - Imino proton exchange and base-pair kinetics in the AMP-RNA aptamer complex.
AB  - We report on the dynamics of base-pair opening in the ATP-binding asymmetric
      internal loop and flanking base-pairs of the AMP-RNA aptamer complex by
      monitoring the exchange characteristics of the extremely well resolved imino
      protons in the NMR spectrum of the complex. The kinetics of imino proton exchange
      as a function of basic pH or added ammonia catalyst are used to measure the
      apparent base-pair dissociation constants and lifetimes of Watson-Crick and
      mismatched base-pairs, as well as the solvent accessibility of the unpaired imino
      protons in the complex. The exchange characteristics of the imino protons
      identify the existence of four additional hydrogen bonds stabilizing the
      conformation of the asymmetric ATP-binding internal loop that were not detected
      by NOEs and coupling constants alone, but are readily accommodated in the
      previously reported solution structure of the AMP-RNA aptamer complex published
      from our laboratory. The hydrogen exchange kinetics of the non-Watson-Crick pairs
      in the asymmetric internal loop of the AMP-RNA aptamer complex have been
      characterized and yield apparent dissociation constants (alphaKd) that range from
      10(-2) to 10(-7). Surprisingly, three of these alphaKd values are amongst the
      lowest measured for all base-pairs in the AMP-RNA aptamer complex. Comparative
      studies of hydrogen exchange of the imino protons in the free RNA aptamer and the
      AMP-RNA aptamer complex establish that complexation stabilizes not only the bases
      within the ATP-binding asymmetric internal loop, but also the flanking stem base
      pairs (two pairs on either side) of the binding site. We also outline some
      preliminary results related to the exchange properties of a sugar 2'-hydroxyl
      proton of a guanosine residue involved in a novel hydrogen bond that has been
      shown to contribute to the immobilization of the bound AMP by the RNA aptamer,
      and whose resonance is narrow and downfield shifted in the spectrum.

PMID- 9159477
TI  - X-ray diffraction analysis of scrapie prion: intermediate and folded structures
      in a peptide containing two putative alpha-helices.
AB  - Small proteinaceous infectious particles called prions cause certain
      neurodegenerative diseases in human and animals. Limited proteolysis of
      infectious scrapie prions PrP(Sc) yields an N-truncated polypeptide termed PrP 27
      30, which encompasses residues 90 to 231 of PrP(Sc) and which assembles into 100
      to 200 A wide amyloid rods. It has been hypothesized that the infectious prion is
      converted from its non-infectious cellular form (PrP(C)) by means of an alpha
      helical to beta-sheet conformational change. Secondary structure analysis,
      computer modeling, and structural biophysics methods support this hypothesis.
      Residues 90 to 145 of PrP, which contain two putative alpha-helical domains H1
      and H2, may be of particular relevance to the disease pathogenesis, as C-terminal
      truncation at residue 145 was found in a patient with an inherited prion disease.
      Moreover, our recent X-ray diffraction analysis suggests that the peptide
      consisting of these residues (designated SHa 90-145) closely models the
      amyloidogenic beta-sheet core of PrP. In the current study, we have analyzed in
      detail the X-ray diffraction patterns of SHa 90-145. Two samples were examined:
      one that was dehydrated under ambient conditions whilst in an external magnetic
      field (to induce fibril orientation), and another that was sealed after partial
      drying. The dried, magnetically oriented sample showed a cross-beta diffraction
      pattern in which the fiber axis (rotation axis) was parallel to the H-bonding
      direction of the beta-sheets. The major wide-angle peaks indicate the presence of
      approximately 40 A wide beta-crystallites, which constitute the protofilament.
      Each crystallite is composed of several orthogonal unit cells, normal to the
      fiber (a-axis) direction, having lattice constants a = 9.69 A, b = 6.54 A, and c
      = 18.06 A. Electron density maps were calculated by iterative Fourier synthesis
      using beta-silk as an initial phase model. The distribution of density indicated
      that there were two types of beta-sheet, suggesting that larger and smaller side
      chains localized to different sheets. This would arise from folding of the
      polypeptide in which there are turns in the middle of both the H1 and H2 domains.
      A monoclinic macrolattice, with a = 9.61 A, b = c = 52.99 A and alpha = 114.6
      degrees, was found to index all the reflections, including those in the low-angle
      region. This suggests that the beta-crystallites are nearly hexagonally packed.
      To account for the approximately 100 A wide fibers visualized by negative
      staining in the electron microscope, the beta-crystallites would be arranged in 4
      mers. The partially dried sample showed a sharp 4.7 A reflection (from H-bonding)
      and five broad peaks superimposed on monotonically decreasing diffuse scattering.
      This solution-like scattering was modeled by an anisometric rectangle with a
      thickness comparable to a singe beta-chain. The structure, which occurred during
      dehydration, could be a transient in the alpha-helical to beta-sheet conversion,
      suggesting that formation of hydrogen bonding precedes the inter-sheet
      interaction and assembly into the amyloid of scrapie prion.

PMID- 9159478
TI  - Crystal structures of the free and liganded form of an esterolytic catalytic
      antibody.
AB  - The crystal structure of the esterase catalytic antibody 48G7 has been determined
      in the presence of hapten at 2.0 A resolution and in the absence of hapten at 2.7
      A resolution. The root-mean-square difference between the two structures is 0.6 A
      for the variable domain and 0.7 A for the constant domain. Comparison of the
      active site shows that no significant changes occur upon hapten binding as main
      chain and side-chain displacements are negligible. Complex formation occurs as
      hapten fits into a pre-formed pocket about 10 A deep. Although 151 water
      molecules were modeled into the 48G7-hapten structure, none are bound in the
      active site. Comparison of the 48G7 structures with those of other published
      ester hydrolysis antibodies illustrates an emerging theme used by esterolytic
      antibodies in binding their (nitro-)phenyl haptens and in hydrolysing their
      cognate esters and carbonates: hapten is bound with the aryl end buried deep in
      the binding pocket, and the phosphonate moiety is responsible for the majority of
      the binding energy to the antibody-hapten interaction.

PMID- 9159479
TI  - Empirical free energy calculations: a blind test and further improvements to the
      method.
AB  - Empirical Gibbs functions estimate free energies of non-covalent reactions
      (deltaG) from atomic coordinates of reaction products (e.g. antibody-antigen
      complexes). The function previously developed by us has four terms that quantify
      the effects of hydrophobic, electrostatic and entropy changes (conformational,
      association) upon complexation. The function was used to calculate delta deltaG
      of ten lysozyme mutants affecting the stability of the HyHEL-10 antibody-lysozyme
      complex. The mutants were computer-modeled from the X-ray structure of the wild
      type, and free energy calculations produced a correlation coefficient of 0.5 with
      the experimental delta deltaG data (average absolute error +/-3 kcal). The
      following changes were then introduced into the Gibbs function: (1) the
      hydrophobic force was made proportional to the molecular surface, as calculated
      by the GEPOL93 algorithm, with the scaling constant of 70 cal/mol/A2; (2)
      calculation of the electrostatics of binding was carried out by the finite
      difference Poisson-Boltzmann algorithm, which employed uniform grid charging,
      dielectric boundary smoothing and charge anti-aliasing; and (3) side-chain
      conformational entropy was estimated from the CONGEN sampling of torsional
      degrees of freedom. In the new calculations, correlation with experimental data
      improved to 0.6 or 0.8 if a single outlying mutant, K96M, was neglected. Analysis
      of the errors remaining in our calculations indicated that molecular mechanics
      based modeling of the mutants, rather than the form of our amended Gibbs
      function, was the main factor limiting the accuracy of the free energy estimates.

PMID- 9159480
TI  - Apoprotein structure in the LH2 complex from Rhodopseudomonas acidophila strain
      10050: modular assembly and protein pigment interactions.
AB  - The refined structure of the peripheral light-harvesting complex from
      Rhodopseudomonas acidophila strain 10050 reveals a membrane protein with protein
      protein interactions in the trans-membrane region exclusively of a van der Waals
      nature. The dominant factors in the formation of the complex appear to be
      extramembranous hydrogen bonds (suggesting that each apoprotein must achieve a
      fold close to its final structure in order to oligomerize), protein-pigment and
      pigment-pigment interactions within the membrane-spanning region. The pigment
      molecules are known to play an important role in the formation of bacterial light
      harvesters, and their extensive mediation of structural contacts within the
      membrane bears this out. Amino acid residues determining the secondary structure
      of the apoproteins influence the oligomeric state of the complex. The assembly of
      the pigment array is governed by the apoproteins of LH2. The particular
      environment of each of the pigment molecules is, however, influenced directly by
      few protein contacts. These contacts produce functional effects that are not
      attributable to a single cause, e.g. the arrangement of an overlapping cycle of
      chromophores not only provides energy delocalisation and storage properties, but
      also has consequences for oligomer size, pigment distortion modes and pigment
      chemical environment, all of which modify the precise function of the complex.
      The evaluation of site energies for the pigment array requires the consideration
      of a number of effects, including heterogeneous pigment distortions, charge
      distributions in the local environment and mechanical interactions.

PMID- 9159481
TI  - Comparison of the three-dimensional structures of recombinant human H and horse L
      ferritins at high resolution.
AB  - Mammalian ferritins are 24-mers assembled from two types of polypeptide chain
      which provide the molecule with different functions. H(eavy) chains catalyse the
      first step in iron storage, the oxidation of iron(II). L(ight) chains promote the
      nucleation of the mineral ferrihydrite enabling storage of iron(III) inside the
      protein shell. We report here the comparison of the three-dimensional structures
      of recombinant human H chain (HuHF) and horse L chain (HoLF) ferritin
      homopolymers, which have been refined at 1.9 A resolution. There is 53% sequence
      identity between these molecules, and the two structures are very similar, the H
      and L subunit alpha-carbons superposing to within 0.5 A rms deviation with 41
      water molecules in common. Nevertheless, there are significant important
      differences which can be related to differences in function. In particular, the
      centres of the four-helix bundles contain distinctive groups of hydrophilic
      residues which have been associated with ferroxidase activity in H chains and
      enhanced stability in L chains. L chains contain a group of glutamates associated
      with mineralisation within the iron storage cavity of the protein.

PMID- 9159482
TI  - Crystal structure of the aspartic proteinase from Rhizomucor miehei at 2.15 A
      resolution.
AB  - The crystal structure of the aspartic proteinase from Rhizomucor miehei (RMP, EC
      3. 4. 23. 23) has been refined to 2.15 A resolution to a crystallographic R-value
      of 0.215 and an Rfree of 0.281. The root-mean-square (r.m.s.) error for the
      atomic coordinates estimated from a Luzzati plot is 0.2 A. The r.m.s. deviations
      for the bond distances and bond angles from ideality are 0.01 A and 1.7 degrees,
      respectively. RMP contains two domains that consist predominantly of beta-sheets.
      A large substrate-binding cleft is clearly visible between the two domains, and
      the two catalytic residues Asp38 and Asp237 are located in the middle of the
      cleft with a water molecule bridging the carboxyl groups of Asp38 and Asp237. Due
      to crystal packing, the C-terminal domain is more mobile than the N-terminal
      domain. Most of the aspartic proteinases (except renin) reach their maximum
      activity at acidic pH. We propose that the optimum pH of each aspartic proteinase
      is determined by the electrostatic potential at the active site, which, in turn,
      is determined by the positions and orientations of all the residues near the
      active site. RMP is the most glycosylated among the aspartic proteinases. The
      carbohydrate moieties are linked to Asn79 and Asn188. Asn79 is in the middle of a
      beta-strand and Asn188 is on a surface loop in contrast to the previous
      hypothesis proposed by Brown and Yada that they are both on surface beta-turns.
      RMP has a very high thermal stability. The high thermal stability is probably due
      to the high level of glycosylation. We propose that the highly flexible
      carbohydrates act as heat reservoirs to stabilize the conformation of RMP and
      therefore give the enzyme a high level of thermal stability. Three-dimensional
      structural and sequence alignments of RMP with other aspartic proteinases show
      that RMP is most structurally homologous to that of Mucor pusillus (MPP), and
      differs from other fungal enzymes as much as it does from the mammalian enzymes.
      This suggests that RMP and MPP diverged from the main stream of aspartic
      proteinases at an early stage of evolution. The present study adds a second
      member to this subfamily of aspartic proteinases.

PMID- 9159483
TI  - Crystal structure of Epstein-Barr virus protein BCRF1, a homolog of cellular
      interleukin-10.
AB  - The crystal structure of Epstein-Barr virus protein BCRF1, an analog of cellular
      interleukin-10 (IL-10), has been determined at the resolution of 1.9 A and
      refined to an R-factor 0.191. The structure of this cytokine is similar to that
      of human IL-10 (hIL-10), forming an intercalated dimer of two 17 kDa polypeptides
      related by a crystallographic 2-fold symmetry axis. BCRF1 exhibits novel
      conformations of the N-terminal coil and of the loop between helices A and B
      compared to hIL-10. These regions are likely to be involved in binding of one or
      more components of the IL-10 receptor system, and thus the structural differences
      may account for the lower binding affinity and limited spectrum of biological
      activities of viral IL-10, compared to hIL-10.

PMID- 9159484
TI  - Solution structure of recombinant human interleukin-6.
AB  - Interleukin-6 (IL-6) is a 185 amino acid cytokine which exerts multiple
      biological effects in vivo and whose dysregulation underlies several disease
      processes. The solution structure of recombinant human interleukin-6 has now been
      determined using heteronuclear three and four-dimensional NMR spectroscopy. The
      structure of the molecule was determined using 3044 distance and torsion
      restraints derived by NMR spectroscopy to generate an ensemble of 32 structures
      using a combined distance geometry/simulated annealing protocol. The protein
      contains five alpha-helices interspersed with variable-length loops; four of
      these helices constitute a classical four-helix bundle with the fifth helix
      located in the CD loop. There were no distance violations greater than 0.3 A in
      any of the final 32 structures and the ensemble has an average-to-the-mean
      backbone root-mean-square deviation of 0.50 A for the core four-helix bundle.
      Although the amino-terminal 19 amino acids are disordered in solution, the
      remainder of the molecule has a well defined structure that shares many features
      displayed by other long-chain four-helix bundle cytokines. The high-resolution
      NMR structure of hIL-6 is used to rationalize available mutagenesis data in terms
      of a heteromeric receptor complex.

PMID- 9159485
TI  - The stability and dynamics of ribosomal protein L9: investigations of a molecular
      strut by amide proton exchange and circular dichroism.
AB  - Nuclear magnetic resonance and circular dichroism experiments were used to
      investigate the stability and dynamic aspects of ribosomal protein L9 from
      Bacillus stearothermophilus in solution. This unusually shaped protein, with its
      two widely spaced RNA-binding domains linked by a connecting helix, has been
      hypothesized to serve as a "molecular strut", most likely playing a role in
      ribosome assembly and/or maintaining the catalytically active conformation of
      ribosomal RNA. Protection factors for amide proton exchange were quantitatively
      measured in an extensive series of NMR experiments, providing probes of the
      stability and dynamics of localized regions of the protein. Results show that
      each of the two RNA-binding domains contains a highly stable core. The exposed
      central helix that connects the two domains is helical in solution, albeit not
      rigid, a result that is supported by amide proton protection factors, circular
      dichroism measurements, and carbon-13 and proton chemical shift index values. A
      conserved glycine and lysine-rich loop in the N-terminal domain is ordered and
      quite stable, a surprising result, since this loop had been presumed to be
      disordered in the original crystallographic analysis. Interestingly, the most
      dynamic parts of the protein are the regions that contain the likely RNA-binding
      residues in each of the two domains. The present results add further support to
      the notion that the L9 protein plays an architectural role within the ribosome,
      with the central helix serving as a molecular strut, or perhaps a spring, linking
      the two widely spaced RNA-binding domains.

PMID- 9159486
TI  - NMR 15N relaxation and structural studies reveal slow conformational exchange in
      barstar C40/82A.
AB  - Barstar an 89-residue protein consisting of four helices and a three-stranded
      parallel beta-sheet, is the intracellular inhibitor of the endoribonuclease
      barnase. Barstar C40/82A, a mutant in which the two cysteine residues have been
      replaced by alanine, has been used as a pseudo wild-type in folding studies and
      in the crystal structure of the barnase:barstar C40/82A complex. We have
      determined a high resolution solution structure of barstar C40/82A. The
      structures of barstar C40/82A and the wild-type are superimposable. A comparison
      with the crystal structure of the barnase:barstar C40/82A complex revealed subtle
      differences in the regions involved in the binding of barstar to barnase. Side
      chain rotations of residues Asn33, Asp35 and Asp39 and a movement of the binding
      loop (Pro27-Glu32) towards the binding site of barnase facilitate the formation
      of interface hydrogen bonds and aromatic contacts in the complex. Extreme line
      broadening and missing signals in 1H-15N correlation spectra indicate substantial
      conformational exchange for a large subset of residues. 15N relaxation data at
      two magnetic field strengths, 11.74 T and 14.10 T, were used to estimate exchange
      contributions and to map the spectral density function at five frequencies: 0,
      50, 60, 450 and 540 MHz. Based on these results, model-free calculations with the
      inclusion of estimated exchange contributions were used to derive order
      parameters and internal correlation times. The validity of this approach has been
      investigated with model-free calculations that incorporate longitudinal
      relaxation rates and heteronuclear 1H-15N NOE data only at 11.74 T and 14.10 T.
      The relaxation data suggest substantial conformational exchange in regions of
      barstar C40/82A, including the binding loop, the second and the third helices,
      and the second and the third strands. Amide proton exchange experiments suggest a
      stable hydrogen bond network for all helices and sheets except the third helix
      and the C-terminal of the second and the third strands. The combined results
      indicate a rigid body movement of the second helix and twisting motions of the
      beta-sheet of barstar, which might be important for the interaction with barnase.

PMID- 9159487
TI  - GroEL-mediated folding of structurally homologous dihydrofolate reductases.
AB  - Using stopped-flow fluorescence techniques, we have examined both the refolding
      and unfolding reactions of four structurally homologous dihydrofolate reductases
      (murine DHFR, wild-type E. coli DHFR, and two E. coli DHFR mutants) in the
      presence and absence of the molecular chaperonin GroEL. We show that GroEL binds
      the unfolded conformation of each DHFR with second order rate constants greater
      than 3 x 10(7) M(-1)s(-1) at 22 degrees C. Once bound to GroEL, the proteins
      refold with rate constants similar to those for folding in the absence of GroEL.
      The overall rate of formation of native enzyme is decreased by the stability of
      the complex between GroEL and the last folding intermediate. For wild-type E.
      coli DHFR, complex formation is transient while for the others, a stable complex
      is formed. The stable complexes are the same regardless of whether they are
      formed from the unfolded or folded DHFR. When complex formation is initiated from
      the native conformation, GroEL binds to a pre-existing non-native conformation,
      presumably a late folding intermediate, rather than to the native state, thus
      shifting the conformational equilibrium toward the non-native species by mass
      action. The model presented here for the interaction of these four proteins with
      GroEL quantitatively describes the difference between the formation of a
      transient complex and a stable complex as defined by the rate constants for
      release and rebinding to GroEL relative to the rate constant for the last folding
      step. Due to this kinetic partitioning, three different mechanisms can be
      proposed for the formation of stable complexes between GroEL and either murine
      DHFR or the two E. coli DHFR mutants. These data show that productive folding of
      GroEL-bound proteins can occur in the absence of nucleotides or the co-chaperonin
      GroES and suggest that transient complex formation may be the functional role of
      GroEL under normal conditions.

PMID- 9159488
TI  - Folding of the disulfide-bonded beta-sheet protein tendamistat: rapid two-state
      folding without hydrophobic collapse.
AB  - We investigated the reversible folding and unfolding reactions of the small 74
      amino acid residue protein tendamistat. The secondary structure of tendamistat
      contains only beta-sheets and loop regions and the protein contains two disulfide
      bonds. Fluorescence-detected refolding kinetics of tendamistat (disulfide bonds
      intact) comprise of a major rapid fast reaction (tau = 10 ms in water) and two
      minor slow reactions. In the fast reaction 80% of the unfolded molecules are
      converted to native protein. The two slow reactions are part of a parallel slow
      folding pathway. On this pathway the rate-limiting step in the formation of
      native molecules is cis to trans isomerization of at least one of the three trans
      Xaa-Pro peptide bonds. This reaction is catalyzed efficiently by the enzyme
      peptidyl-prolyl cis-trans isomerase. Comparison of kinetic data with equilibrium
      unfolding transitions shows that the fast folding pathway follows a two-state
      process without populated intermediate states. Additionally, various sensitive
      tests did not detect any rapid chain collapse during tendamistat folding prior to
      the acquisition of the native three-dimensional structure. These results show
      that pre-formed disulfide bonds do not prevent efficient and rapid protein
      folding.

PMID- 9159489
TI  - Global self-organization of all known protein sequences reveals inherent
      biological signatures.
AB  - A global classification of all currently known protein sequences is performed.
      Every protein sequence is partitioned into segments of 50 amino acid residues and
      a dynamic programming distance is calculated between each pair of segments. This
      space of segments is initially embedded into Euclidean space. The algorithm that
      we apply embeds every finite metric space into Euclidean space so that (1) the
      dimension of the host space is small, (2) the metric distortion is small. A novel
      self-organized, cross-validated clustering algorithm is then applied to the
      embedded space with Euclidean distances. We monitor the validity of our
      clustering by randomly splitting the data into two parts and performing an
      hierarchical clustering algorithm independently on each part. At every level of
      the hierarchy we cross-validate the clusters in one part with the clusters in the
      other. The resulting hierarchical tree of clusters offers a new representation of
      protein sequences and families, which compares favorably with the most updated
      classifications based on functional and structural data about proteins. Some of
      the known families clustered into well distinct clusters. Motifs and domains such
      as the zinc finger, EF hand, homeobox, EGF-like and others are automatically
      correctly identified, and relations between protein families are revealed by
      examining the splits along the tree. This clustering leads to a novel
      representation of protein families, from which functional biological kinship of
      protein families can be deduced, as demonstrated for the transporter family.
      Finally, we introduce a new concise representation for complete proteins that is
      very useful in presenting multiple alignments, and in searching for close
      relatives in the database. The self-organization method presented is very general
      and applies to any data with a consistent and computable measure of similarity
      between data items.

PMID- 9159490
TI  - Dissecting the energetics of a protein-protein interaction: the binding of
      ovomucoid third domain to elastase.
AB  - An understanding of the structural basis for protein-protein interactions, and
      molecular recognition in general, requires complete characterization of binding
      energetics. Not only does this include quantification of the changes that occur
      in all of the thermodynamic parameters upon binding, including the enthalpy,
      entropy and heat capacity, but a description of how these changes are modulated
      by environmental conditions, most notably pH. Here, we have investigated the
      binding of turkey ovomucoid third domain (OMTKY3), a potent serine protease
      inhibitor, to the serine protease porcine pancreatic elastase (PPE) using
      isothermal titration calorimetry and structure-based thermodynamic calculations.
      We find that near neutral pH the binding energetics are influenced by a shift in
      the pKa of an ionizable group, most likely histidine 57 in the protease active
      site. Consequently, the observed binding energetics are strongly dependent upon
      solution conditions. Through a global analysis, the intrinsic energetics of
      binding have been determined, as have those associated with the pKa shift. The
      protonation energetics suggest that the drop in pKa is largely due to desolvation
      of the histidine residue. The resulting deprotonation is necessary for the
      enzymatic function of elastase. Intrinsically, at 25 degrees C the binding of
      OMTKY3 to PPE is characterized by an almost negligible enthalpy change, a large
      positive entropy change, and a large negative heat capacity change. These
      parameters are consistent with a model of the OMTKY3-PPE complex, which shows a
      large and significantly apolar protein-protein interface. Thermodynamic
      calculations based upon changes that occur in polar and apolar solvent-accessible
      surface area are in very good agreement with the measured intrinsic binding
      energetics.

PMID- 9159491
TI  - Electrostatic complementarity at protein/protein interfaces.
AB  - Calculation of the electrostatic potential of protein-protein complexes has led
      to the general assertion that protein-protein interfaces display "charge
      complementarity" and "electrostatic complementarity". In this study, quantitative
      measures for these two terms are developed and used to investigate protein
      protein interfaces in a rigorous manner. Charge complementarity (CC) was defined
      using the correlation of charges on nearest neighbour atoms at the interface. All
      12 protein-protein interfaces studied had insignificantly small CC values.
      Therefore, the term charge complementarity is not appropriate for the description
      of protein-protein interfaces when used in the sense measured by CC.
      Electrostatic complementarity (EC) was defined using the correlation of surface
      electrostatic potential at protein-protein interfaces. All twelve protein-protein
      interfaces studied had significant EC values, and thus the assertion that protein
      protein association involves surfaces with complementary electrostatic potential
      was substantially confirmed. The term electrostatic complementarity can therefore
      be used to describe protein-protein interfaces when used in the sense measured by
      EC. Taken together, the results for CC and EC demonstrate the relevance of the
      long-range effects of charges, as described by the electrostatic potential at the
      binding interface. The EC value did not partition the complexes by type such as
      antigen-antibody and proteinase-inhibitor, as measures of the geometrical
      complementarity at protein-protein interfaces have done. The EC value was also
      not directly related to the number of salt bridges in the interface, and
      neutralisation of these salt bridges showed that other charges also contributed
      significantly to electrostatic complementarity and electrostatic interactions
      between the proteins. Electrostatic complementarity as defined by EC was extended
      to investigate the electrostatic similarity at the surface of influenza virus
      neuraminidase where the epitopes of two monoclonal antibodies, NC10 and NC41,
      overlap. Although NC10 and NC41 both have quite high values of EC for their
      interaction with neuraminidase, the similarity in electrostatic potential
      generated by the two on the overlapping region of the epitopes is insignificant.
      Thus, it is possible for two antibodies to recognise the electrostatic surface of
      a protein in dissimilar ways.

PMID- 9159492
TI  - Transforming growth factor-beta1 induces apoptosis of rat microglia without
      relation to bcl-2 oncoprotein expression.
AB  - Transforming growth factor-beta (TGF-beta) plays a role as an immunosuppressive
      cytokine within the central nervous system (CNS). The CNS cells targeted by
      action of TGF-beta1 have not been defined. In this study, we tested the effect of
      TGF-beta1 on microglia, astrocytes and oligodendrocytes from newborn rats. TGF
      beta1 selectively induced apoptosis of microglia, and not of astrocytes or
      oligodendrocytes. To study the apoptotic mechanism, bcl-2 oncoprotein expression
      in microglia, astrocytes and oligodendrocytes was measured. Bcl-2 was mainly
      expressed in microglia, indicating that microglial bcl-2 does not prevent TGF
      beta1-mediated microglial apoptosis. The relative protein expression of bcl-2 in
      microglia was not related to frequency of microglial apoptosis. Thus, TGF-beta1
      induced microglial apoptosis was regulated by a bcl-2-independent mechanism.
      Expression of cytokine (IL-1beta, IL-6, IL-12, IFN-gamma and TNF-alpha) mRNA on
      microglia was not influenced by treatment with TGF-beta1.

PMID- 9159494
TI  - Characterisation of the binding of [3H]MDL 105,519, a radiolabelled antagonist
      for the N-methyl-D-aspartate-associated glycine site, to pig cortical brain
      membranes.
AB  - Binding of [3H]MDL 105,519 to glycine sites on N-methyl-D-aspartate (NMDA)
      receptors of pig cortical brain membranes was evaluated. [3H]MDL 105,519 labelled
      a homogeneous population of binding sites with a Kd-value of 3.73 +/- 0.43 nM and
      a Bmax-value of 3030 +/- 330 fmol/mg protein. Clear correlations between the
      affinity (Ki) to [3H]MDL 105,519 labelled sites and the potency (EC50) to enhance
      or inhibit non-equilibrium [3H]MK-801 binding in the nominal absence of glycine
      were shown for a variety of glycine site agonists, partial agonists and
      antagonists. The ratio of Ki to EC50 was >1 for agonists and partial agonists and
      <1 for antagonists. Various cations as well as glutamate and polyamine site
      ligands were shown to be able to influence [3H]MDL 105,519 binding to pig
      cortical brain membranes substantially.

PMID- 9159493
TI  - Suppression of the oxidative burst in murine microglia by nitric oxide.
AB  - The effect of nitric oxide (NO) on the oxidative burst was analyzed in purified
      murine microglial cells in vitro. The generation of reactive oxygen derivatives
      was monitored with the use of luminol-dependent chemiluminescence. After inducing
      the endogenous NO production with interleukin 1beta (IL-1beta) and interferon
      gamma (IFN-gamma) the superoxide anion release was significantly reduced, which
      was reversed by the inhibition of the NO synthase. Additionally, chemical NO
      releasing compounds reduced the generation of reactive oxygen derivatives rapidly
      and independently of the pathway used to trigger the oxidative burst. This effect
      of NO was not mediated via guanylyl cyclase and cGMP, or due to the scavenging of
      released superoxide anions. This attenuation of superoxide anion generation by NO
      may limit deleterious effects of the release of reactive oxygen derivatives in
      tissue inflammation or injury.

PMID- 9159495
TI  - GABA(B) receptor blockade reduces resistive loading-induced hypoventilation in
      anesthetized rabbits.
AB  - We hypothesized that hypoventilation induced by resistive loaded breathing may
      result in part from the inhibition of central respiratory-related structures by
      gamma-aminobutyric acid (GABA), through the stimulation of GABA(B) receptors. In
      that case, ventilatory depression should be minimized by GABA(B) receptor
      blockade. To test this assumption, the ventilatory effects of a GABA(B) receptor
      antagonist (CGP 35348) were evaluated in two groups of urethane anesthetized
      rabbits, breathing either through an inspiratory resistive load (IRL group) or
      not (Control group). CGP 35348 did not modify baseline ventilation in the Control
      group. On the other hand, it partially reversed IRL-induced hypoventilation
      through a higher respiratory rate and central inspiratory drive. These data
      suggest that, unlike GABA(A) receptors, GABA(B) receptors would not play a part
      in eupneic breathing, but that they could participate in the hypoventilation
      resulting from an acute increase in the work of breathing.

PMID- 9159496
TI  - Wisconsin card sorting test and Stroop test performance in schizophrenia: a
      shared construct.
AB  - The Wisconsin card sorting test (WCST) and Stroop test were administered to 25
      schizophrenic patients in order to better identify and understand more specific
      processing mechanisms involved in executive dysfunctions and to investigate their
      hypothetical involvement in symptom formation. Data show that for as much as the
      two tests employed measured executive functions in terms of mental control and
      cognitive flexibility, our findings seemed to indicate shared or interconnected
      mechanisms. No correlations were seen between the psychopathological evaluation
      and any of the neuropsychological indexes. The use of the Stroop task could
      provide a more readily cognitive analysis in terms of specific processing
      mechanisms, at the basis of WCST impairment in schizophrenia.

PMID- 9159498
TI  - Phenytoin and carbamazepine: differential inhibition of sodium currents in small
      cells from adult rat dorsal root ganglia.
AB  - We determined the effects of carbamazepine and phenytoin, anticonvulsant drugs
      used to treat neuropathic pain, on the heterogeneous population of Na+ channels
      in patch-clamped small cells from adult rat dorsal root ganglia. Both fast
      tetrodotoxin-sensitive (TTX-S) and slow TTX-resistant (TTX-R) currents were
      inhibited by 10-100 microM drug. TTX-R currents were divided into two classes.
      Control type I currents had a very depolarized voltage for 50% availability (Vh)
      of ca. -29 mV and 17% reduction in current by the 20th pulse at 1 Hz. Control
      type II currents had a Vh closer to -46 mV and 49% reduction in current at 1 Hz.
      At 0.1 Hz, which gave relatively little loss of control current, 100 microM drug
      caused 53 +/- 4% (n = 5) block of type I current and 88 +/- 2% inhibition of type
      II current (n = 4). Strong 1 s hyperpolarizing prepulses relieved most of the
      fast channel block but had much less effect on blocked TTX-R channels.

PMID- 9159497
TI  - Agonist-induced [35S]GTPgammaS binding in the membranes of Spodoptera frugiperda
      insect cells expressing the human D3 dopamine receptor.
AB  - In the membranes of Spodoptera frugiperda (Sf-9) insect cells heterologously
      expressing the human D3 dopamine receptor, agonists selective for the receptor,
      but not antagonists, robustly enhanced [35S]GTPgammaS binding. Quinpirole, for
      instance, dose-dependently enhanced [35S]GTPgammaS binding with a half-maximal
      concentration of 2.3 +/- 0.2 nM. Its action was absent in the cells infected with
      wild type viruses, and competitively blocked by an antagonist, YM-09151-2. A
      number of known agonists enhanced [35S]GTPgammaS binding to variable degrees,
      probably reflecting their differential efficacy to activate target G-proteins via
      the receptor. This agonist-induced [35S]GTPgammaS binding was abolished by N
      ethylmaleimide, a selective blocking agent for Gi/Go proteins, with no
      appreciable effect on ligand binding. We propose coupling of the cloned D3
      receptor to endogenous G-proteins in Sf-9 cells, probably homologs of mammalian
      Gi/Go proteins. Despite the apparent coupling of the D3 receptor to G-proteins,
      GTPgammaS (10 microM) failed to decrease agonist binding ([3H]dopamine) to the D3
      receptor, probably due to small affinity differences between low and high
      affinity states for agonists in the D3 receptor, as well as due to high receptor
      density in Sf-9 cells. We conclude that agonist-induced [35S]GTPgammaS binding
      for the D3 receptor is suitable for estimating ligand intrinsic efficacy and
      pharmacological characterizations of ligand-receptor interactions.

PMID- 9159499
TI  - Distribution of neuronal nitric oxide synthase in the rat liver.
AB  - We studied the distribution of neuronal nitric oxide synthase (nNOS) in the rat
      liver with a specific polyclonal antibody by using immunocytochemical procedures
      in the light microscopic level. Immunoreactive varicose nerve fibers were found
      forming a dense plexus around the interlobular hepatic artery and the
      interlobular bile duct in the hepatic hilus, and in the hepatic artery
      ramifications of the portal triads. The density of nNOS positive nerve fibers
      decreases with successive portal ramifications, and some non-immune positive
      nerve fibers were found in the distal portions of the arterial vessels. The
      presence of the nNOS positive nerve fibers suggests that the possible main
      functional role could be related with the regulation of hepatic blood circulation
      and hepatobiliary activities.

PMID- 9159500
TI  - Disturbances of precision grip in Huntington's disease.
AB  - Disturbed motor control of the fingers, as revealed by the response to unexpected
      loading of an object held in a precision grip, or to finger perturbation during
      isometric holding, has been studied in patients with Huntington's disease (HD)
      and in normal subjects. In normal subjects unexpected loading elicited a reflex
      response (mean latency 73 ms) in the first dorsal interosseus muscle (FDI). This
      was accompanied by a clear increase in grip force, reaching a maximum at 200 ms,
      which stabilised block position. Index finger perturbation led to a long-latency
      reflex response in the FDI of all normal subjects. No such response was seen in
      the HD patients. The response to object loading, in contrast, was present, but
      significantly delayed (mean onset 95 ms; P = 0.0135). The response was
      qualitatively normal, with grip force reaching a maximum at 220-230 ms. It is
      suggested that the absence of the long-latency stretch reflex and the delay in
      the response to loading in HD patients may represent a reduction in somatosensory
      input to the cortex caused by disruption of basal ganglia structures.

PMID- 9159501
TI  - Long-term potentiation and long-term depression are induced through
      pharmacologically distinct NMDA receptors.
AB  - N-Methyl-D-aspartate (NMDA) receptor activation initiates both homosynaptic long
      term depression (LTD) and long-term potentiation (LTP) in the CA1 region of the
      hippocampus. The mechanism by which two opposing forms of synaptic plasticity can
      be initiated through the activation of a single receptor is not known. We
      examined the effects of two competitive antagonists on the induction of LTP and
      LTD, D-2-amino-5-phosphonovaleric acid (D-AP5), a broad spectrum inhibitor of the
      NMDA receptor, and 3-((RS)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
      (CPP), an antagonist that binds with high affinity to conventional NMDA receptors
      subtypes, but not to atypical subtypes that are relatively independent of voltage
      dependent Mg2+-blockade. As has previously been reported, LTP, LTD, and
      depotentiation were all blocked by applications of D-AP5. In contrast, only LTP,
      but not LTD or depotentiation, was blocked by CPP. These observations suggest
      that decreases and increases of synaptic strength are mediated by the activation
      of distinct NMDA receptor subpopulations.

PMID- 9159502
TI  - Excitotoxic lesions of the pedunculopontine tegmental nucleus produce
      contralateral hemiparkinsonism in the monkey.
AB  - Dopaminergic nigrostriatal neurons, degeneration of which causes Parkinson's
      disease, are known to receive excitatory input almost exclusively from the
      pedunculopontine tegmental nucleus (PPN). We report here that excitotoxic lesions
      of the PPN produce abnormal motor signs relevant to hemiparkinsonism in the
      macaque monkey. Under the guidance of extracellular unit recordings, the
      electrophysiologically identified PPN was injected unilaterally with kainic acid.
      These PPN-lesioned monkeys exhibited mild to moderate levels of flexed posture
      and hypokinesia in the upper and lower limbs contralateral to the lesion. In most
      of the monkeys, such pathophysiological events were gradually improved and became
      stationary in 1-2 weeks. The hemiparkinsonian symptoms observed after PPN
      destruction might be ascribed to a decrease in nigrostriatal neuron activity due
      to excitatory input ablation.

PMID- 9159503
TI  - Administration of corticosterone alters intracellular localization of brain
      derived neurotrophic factor-like immunoreactivity in the rat brain.
AB  - We investigated the distribution of immunoreactivity for brain-derived
      neurotrophic factor (BDNF) in rat brain after peripheral administration of
      corticosterone or vehicle. In the immunohistochemical study, BDNF-like
      immunoreactivity (LI) was observed predominantly in the nucleus of the cortical
      and hippocampal neurons in the brain of vehicle-treated rats. In corticosterone
      treated rats, BDNF-LI was markedly reduced in the nucleus and concomitantly
      increased in cytoplasm. Western immunoblot study also demonstrated that
      corticosterone significantly reduced BDNF-LI in the nuclear fraction of the
      cerebral cortex and hippocampus. These results indicate that corticostrone
      regulates the intracellular localization of BDNF and/or its derivatives in the
      rat brain.

PMID- 9159504
TI  - Melatonin suppresses hyperglycemia caused by intracerebroventricular injection of
      2-deoxy-D-glucose in rats.
AB  - To elucidate the role of melatonin (MT), we examined the effects of intracranial
      injection of MT and an MT-antagonist (S20928) on the hyperglycemic response to
      intracranial injection of 2-deoxy-D-glucose (2DG) in rats. The hyperglycemic and
      hyperglucagonemic responses caused by intracerebroventricular injection of 2DG
      were inhibited by intracerebroventricular co-injection of MT, but enhanced by co
      injection of the MT-antagonist. Intraperitoneal injection of MT also inhibited
      the hyperglycemic response, though the inhibition seemed to be less than that
      after intracranial injection of MT. These results suggest that MT plays an
      endogenously suppressive role in the hyperglycemia caused by 2DG, possibly
      through a brain site.

PMID- 9159505
TI  - The neurosteroid pregnenolone sulphate enhances NMDA-induced phasic firing of
      vasopressin neurones in the rat supraoptic nucleus.
AB  - The effect of the neurosteroid pregnenolone sulphate (PS) on N-methyl-D-aspartate
      (NMDA)-induced phasic firing of supraoptic vasopressin (VP) neurones was studied
      in rat hypothalamic slices in vitro. In VP neurones which were induced to fire
      phasically by continuous perifusion with NMDA (9-30 microM), addition of 100
      microM PS to the incubation medium significantly increased overall spike
      frequency, with a rise in both proportion of time active and intraburst firing
      rate. A similar effect was seen during picrotoxin block of GABAergic
      transmission. No significant change in NMDA-induced phasic firing was observed
      with 100 microM dehydroepiandrosterone sulphate. VP neurones became silent in the
      absence of NMDA, and under these conditions PS had no effect. In conclusion, PS
      increases NMDA-induced phasic firing in VP neurones, providing a mechanism
      whereby this neurosteroid may participate in the regulation of VP secretion.

PMID- 9159506
TI  - Gustatory and visceral inputs to the amygdala of the rat: conditioned taste
      aversion and induction of c-fos-like immunoreactivity.
AB  - Expression of proto-oncogene c-fos was immunohistochemically examined in the
      central and basolateral amygdaloid nuclei in rats after ingestion of taste
      solutions (0.5 M sucrose or 0.005 M saccharin), intragastric infusion of these
      solutions, or an intraperitoneal injection of malaise-inducing lithium chloride
      (LiCl). C-Fos-like immunoreactive neurons were distributed most densely in the
      central nucleus in response to the LiCl injection, followed by the ingestion and
      intragastric infusion of sucrose. The intraoral infusion of sucrose, but not of
      saccharin, elicited intense c-fos expression in the central nucleus after
      establishment of conditioned taste aversion to these taste stimuli. The results
      are discussed in terms of post-ingestional factors and the conditioned illness
      reaction after taste aversion learning.

PMID- 9159507
TI  - Voltammetric detection of nitric oxide (NO) in the rat brain: its variations
      throughout the sleep-wake cycle.
AB  - A sensor allowing the specific detection of nitric oxide (NO) is reported.
      Together with differential pulsed voltammetry, it allows the detection of a 650
      mV signal either in NO solutions or in the rat frontal cortex. The
      intraperitoneal (i.p.) administration of a NO donor (S-nitrosoglutathione, 20
      mg/kg i.p.) increases the signal height (+30%) while that of a nitric oxide
      synthase (NOS) inhibitor like L-nitro-arginine-p-nitro-anilide (100 mg/kg i.p.),
      produces its complete disappearance in the cortex of anesthetized rats. These
      results suggest that the 650 mV signal might be NO-dependent. Some other NOS
      inhibitors have been found either inefficient (L-nitro-arginine-methyl-ester) or
      partially efficient (7-nitro-indazole) on the signal height. In freely moving
      rats, also equipped with polygraphic electrodes, the signal measured in the
      frontal cortex exhibits the highest height during waking. It decreases during
      slow-wave sleep (-6%) and paradoxical sleep (-9%).

PMID- 9159508
TI  - Effects of iontophoretically applied serotonin on three classes of
      physiologically characterized putative pain modulating neurons in the rostral
      ventromedial medulla of lightly anesthetized rats.
AB  - The importance of the rostral ventromedial medulla (RVM) in nociceptive
      modulation is well documented, and several lines of evidence point to a role for
      serotonin (5HT) in regulating the activity of pain modulating neurons in this
      region. The aim of the present study was to examine the effect of
      iontophoretically applied 5HT upon the firing of three physiologically defined
      classes of RVM neurons with distinct roles in pain modulation. The predominant
      effect across all classes was a facilitation of ongoing or evoked activity. A
      minority of cells within each class were inhibited by 5HT itself, but agonists at
      5HT1 receptor types inhibited the majority of cells tested. The results thus
      indicate that the behavioral effects of manipulating 5HT within the RVM cannot be
      attributed to a selective influence on a particular cell class.

PMID- 9159509
TI  - Effect of tunicamycin on histological organization and Na, K-ATPase distribution
      in the adult cat retina.
AB  - Intravitreal injection of tunicamycin (TM) was evaluated as a method for inducing
      photoreceptor-specific degeneration in cat retina. TM (1 microg, 5-weeks
      duration) markedly decreased electroretinogram amplitudes. A polyclonal antibody
      directed against the Na, K-ATPase was used to further assess cell-specific
      retinal injury induced by TM. TM-treatment induced marked alterations in the
      differential distribution of the Na, K-ATPase within the retina. Histology
      confirmed photoreceptor degeneration in TM-treated retina, but further showed a
      severe, non-selective degradation of most retinal layers. Therefore, long-term
      intraocular exposure to TM results in a progressive general toxicity to the cat
      retina.

PMID- 9159510
TI  - Regulation of the Caulobacter flagellar gene hierarchy; not just for motility.
AB  - The Caulobacter crescentus flagellum serves not only as a motility apparatus, but
      also as a key landmark in the differentiation of this asymmetrically dividing
      bacterium. A distinctive aspect of flagellum biosynthesis is the periodic
      expression of the flagellar genes during the cell cycle in a sequence
      corresponding to the order of gene product assembly into the growing flagellum.
      This program of gene expression is achieved in part by the organization of
      flagellar genes into a four-tiered regulatory hierarchy that controls their
      expression at both the transcriptional and post-transcriptional levels. Because
      of the close interconnection of the developmental program to the asymmetric cell
      division cycle in C. crescentus, studies of flagellar gene regulation and
      motility have also begun to reveal basic mechanisms responsible for control of
      the cell cycle itself. Here, we review recent work on regulation of the flagellar
      gene hierarchy in C. crescentus and consider regulatory mechanisms that are
      distinct from those described in Escherichia coli and Salmonella typhimurium.

PMID- 9159511
TI  - Dynamic bacterial genome organization.
AB  - Recently completed projects of sequencing chromosomal fragments and entire
      chromosomes, as well as physical mapping of genomes, have opened novel inroads to
      the understanding of the biology of bacterial genomes. From these studies one may
      draw some conclusions. (i) The organization of orthologous genes on the bacterial
      chromosome is not conserved during evolution. (ii) The bacterial genome is more
      complex and also more flexible than hitherto thought. Genetic elements are
      sometimes part of the chromosome, while at other times they are independent
      elements or parts of alternative replicons (e.g. large plasmids). Such replicons,
      carrying essential genes, now seem to deserve the designation 'secondary
      chromosomes'. A study of the regulation of replication and segregation of these
      essential genetic elements will be of great interest.

PMID- 9159512
TI  - Getting greasy: how transmembrane polypeptide segments integrate into the lipid
      bilayer.
AB  - Many integral membrane proteins use the same translocation machinery for membrane
      insertion as secretory proteins use to get across the membrane. This requires
      that transmembrane segments can be discriminated from other parts of the protein
      during membrane translocation, and further requires that the transmembrane
      segments can be moved laterally out of the translocation channel into the
      surrounding lipid. The molecular basis for this remarkable intramembraneous
      sorting event is a major focus of current studies of membrane protein biogenesis.

PMID- 9159513
TI  - The Escherichia coli phage-shock-protein (psp) operon.
AB  - The phage-shock-protein (psp) operon helps to ensure survival of Escherichia coli
      in late stationary phase at alkaline pH, and protects the cell against
      dissipation of its proton-motive force against challenge. It is strongly induced
      by filamentous phage pIV and its bacterial homologues, and by mutant porins that
      don't localize properly, as well as by a number of other stresses. Transcription
      of the operon is dependent on sigma54 and a constitutively active, autogenously
      controlled activator. psp-operon expression is controlled by one negatively and
      several positively acting regulators, none of which is a DNA-binding protein. The
      major product of the operon, PspA, may also serve as a negative regulator of an
      unusual porin, OmpG.

PMID- 9159514
TI  - Biochemistry and molecular genetics of cell-wall lipid biosynthesis in
      mycobacteria.
AB  - Tuberculosis and other mycobacterial infections are the most serious infectious
      diseases in terms of human fatalities. The high content of unique cell-wall
      lipids helps these organisms to resist antimicrobial drugs and host defences. The
      biosynthesis of these lipids is discussed briefly. The recent advances in
      recombinant DNA technology have begun to help to elucidate the nature of some of
      the enzymes involved in this process and the genes that encode them. Gene
      disruption and other molecular genetic technologies are beginning to provide new
      approaches to test for the biological functions of these gene products and may
      lead to identification of new antimycobacterial drug targets.

PMID- 9159515
TI  - TonB protein appears to transduce energy by shuttling between the cytoplasmic
      membrane and the outer membrane in Escherichia coli.
AB  - The energy source for active transport of iron-siderophore complexes and vitamin
      B12 across the outer membrane in Gram-negative bacteria is the cytoplasmic
      membrane proton-motive force (pmf). TonB protein is required in this process to
      transduce cytoplasmic membrane energy to the outer membrane. In this study,
      Escherichia coli TonB was found to be distributed in sucrose density gradients
      approximately equally between the cytoplasmic membrane and the outer membrane
      fractions, while two proteins with which it is known to interact, ExbB and ExbD,
      as well as the NADH oxidase activity characteristic of the cytoplasmic membrane,
      were localized in the cytoplasmic membrane fraction. Neither the N-terminus of
      TonB nor the cytoplasmic membrane pmf, both of which are essential for TonB
      activity, were required for TonB to associate with the outer membrane. When the
      TonB C-terminus was absent, TonB was found associated with the cytoplasmic
      membrane, suggesting that the C-terminus was required for outer membrane
      association. When ExbB and ExbD, as well as their cross-talk-competent homologues
      ToIQ and ToIR, were absent, TonB was found associated with the outer membrane.
      TetA-TonB protein, which cannot interact with ExbB/D, was likewise found
      associated with the outer membrane. These results indicated that the role of
      ExbB/D in energy transduction is to bring TonB that has reached the outer
      membrane back to associate with the cytoplasmic membrane. Two possible
      explanations exist for the observations presented in this study. One possibility
      is that TonB transduces energy by shuttling between membranes, and, at some
      stages in the energy-transduction cycle, is associated with either the
      cytoplasmic membrane or the outer membrane, but not with both at the same time.
      This hypothesis, together with the alternative interpretation that TonB remains
      localized in the cytoplasmic membrane and changes its affinity for the outer and
      cytoplasmic membrane during energy transduction, are incorporated with previous
      observations into two new models, consistent with the novel aspects of this
      system, that describe a mechanism for TonB-dependent energy transduction.

PMID- 9159516
TI  - Pheromone cCF10 and plasmid pCF10-encoded regulatory molecules act post
      transcriptionally to activate expression of downstream conjugation functions.
AB  - Expression of aggregation protein Asc10 from the prgB gene of conjugative plasmid
      pCF10 in Enterococcus faecalis is induced by the peptide pheromone cCF10. Genes
      required for Asc10 production, prgQ and prgS, lie 3-5 kb upstream, but can
      function at much greater distances. The prgQ transcripts encode a pheromone
      inhibitor peptide (iCF10) at the extreme 5' end. Neither production of this
      peptide nor translation of the 5' end of prgQ transcripts was found to be
      necessary for prgB expression. Pheromone cCF10 is required to activate prgB
      expression, even in the absence of iCF10 production, and does not affect
      initiation of transcription. The prgS gene encodes a 10.5 kDa protein that
      appears to be required for translation of prgB, and a non-coding RNA at the 3'
      end of prgS may be required for readthrough of transcription to prgB from the
      prgQ promoter. Although the entire positive control region is transcribed
      constitutively from the prgQ promoter, translation of PrgS and transcriptional
      readthrough to prgB occur only after induction with pheromone. The combined data
      are consistent with a model in which the positive regulatory molecules and
      pheromone cCF10 activate prgB expression post-transcriptionally.

PMID- 9159517
TI  - Pheromone-inducible expression of an aggregation protein in Enterococcus faecalis
      requires interaction of a plasmid-encoded RNA with components of the ribosome.
AB  - Transfer of the conjugative plasmid pCF10 from Enterococcus faecalis donor
      strains is induced by a peptide pheromone (cCF10) secreted by recipient cells.
      High-efficiency transfer requires expression of an aggregation protein (Asc10)
      encoded by the prgB gene and positively regulated by genes in a region 3-5 kb
      upstream, containing prgQ-R-S. Transcriptional fusion data reported here support
      the results of recent molecular analysis of the 5' ends of prgB transcripts which
      indicated that prgB transcription occurs by readthrough from the prgQ promoter. A
      530-nucleotide prgQ-encoded RNA molecule (Q(L)) with rRNA-like domains is
      required for Asc10 production. Q(L) and cCF10 were found to interact with the L6
      and S5 ribosomal proteins, respectively. Mutational analysis of Q(L) indicates
      that this RNA may also directly interact with 16S RNA. Q(L) is present in
      ribosomes translating the prgB message, and pheromone cCF10 may affect the
      association of this RNA with translation complexes. Results suggest that the
      positive regulatory molecules act post-transcriptionally on the polycistronic
      message and modify a ribosome population to enhance pheromone-induced translation
      of prgB.

PMID- 9159518
TI  - The global activator GacA of Pseudomonas aeruginosa PAO positively controls the
      production of the autoinducer N-butyryl-homoserine lactone and the formation of
      the virulence factors pyocyanin, cyanide, and lipase.
AB  - The global activator GacA, a highly conserved response regulator in Gram-negative
      bacteria, is required for the production of exoenzymes and secondary metabolites
      in Pseudomonas spp. The gacA gene of Pseudomonas aeruginosa PAO1 was isolated and
      its role in cell-density-dependent gene expression was characterized. Mutational
      inactivation of gacA resulted in delayed and reduced formation of the cell
      density signal N-butyryl-L-homoserine lactone (BHL), of the cognate
      transcriptional activator RhIR (VsmR), and of the transcriptional activator LasR,
      which is known to positively regulate RhIR expression. Amplification of gacA on a
      multicopy plasmid caused precocious and enhanced production of BHL, RhIR and
      LasR. In parallel, the gacA gene dosage markedly influenced the BHL/RhIR
      dependent formation of the cytotoxic compounds pyocyanin and cyanide and the
      exoenzyme lipase. However, the concentrations of another known cell-density
      signal of P. aeruginosa, N-oxododecanoyl-L-homoserine lactone, did not always
      match BHL concentrations. A model accounting for these observations places GacA
      function upstream of LasR and RhIR in the complex, cell-density-dependent signal
      transduction pathway regulating several exoproducts and virulence factors of P.
      aeruginosa via BHL.

PMID- 9159519
TI  - Intercontinental spread of promiscuous mercury-resistance transposons in
      environmental bacteria.
AB  - We demonstrate that horizontal spread of mer operons similar to worldwide spread
      of antibiotic-resistance genes in medically important bacteria occurred in
      bacteria found in ores, soils and waters. The spread was mediated by different
      transposons and plasmids. Some of the spreading transposons were damaged in
      different ways but this did not prevent their further spread. Certain transposons
      are mosaics composed of segments belonging to distinct sequence types. These
      mosaics arose as a result of homologous and site-specific recombination. Our data
      suggest that the mercury-resistance operons of Gram-negative environmental
      bacteria can be considered as a worldwide population composed of a relatively
      small number of distinct recombining clones shared, at least partially, by
      environmental and clinical bacteria.

PMID- 9159520
TI  - A gene required for nuclear migration in Neurospora crassa codes for a protein
      with cysteine-rich, LIM/RING-like domains.
AB  - The ro mutants of Neurospora crassa are defective in nuclear migration and hyphal
      morphogenesis. Several of the ro loci have recently been shown to encode
      components of the dynein/dynactin motor complex. Here we report on the cloning
      and characterization of the ro-2 gene which codes for a novel 80 kDa protein that
      has two Cys-rich motifs which resemble zinc-binding LIM or RING domains thought
      to mediate protein-protein interactions. RO2 also contains several potential
      binding sites for Src homology 3 (SH3) domains. The ro-2B20 allele has a
      frameshift mutation within one of the Cys-rich domains which eliminates the C
      terminal half of the open reading frame (ORF). Disruption of the ro-2 locus by
      repeat-induced point (RIP) mutation gave rise to progeny which have a nuclear
      migration defect, but which are also blocked in conidiation. The ability to
      assemble cytoplasmic microtubules and actin is maintained in ro-2 mutants,
      although subapical actin patches are more prominent. Based on these observations,
      the RO2 gene product is proposed to play a role in mediating interactions between
      components of the dynein/dynactin motor complex or in linking this complex to the
      nucleus or cytoskeleton.

PMID- 9159521
TI  - Mutations of the coat protein gene of bacteriophage lambda that overcome the
      necessity for the Fl gene; the EFi domain.
AB  - The functions of most of the 10 genes involved in phage lambda capsid
      morphogenesis are well understood. The function of the FI gene is one of the
      exceptions. Mutants in FI fail to mature and package DNA. The gene product (gpFI)
      seems to act as a catalyst for the formation of an intermediate in capsid
      assembly called complex II, which contains a procapsid (an empty capsid
      precursor), terminase (the enzyme that cleaves the DNA precursor and packages it
      into the procapsid) and DNA. The mechanism for this stimulation remains unknown.
      It has also been reported that gpFI appeared to stimulate terminase-mediated cos
      cleavage, in the absence of procapsids, by increasing enzyme turnover. In
      comparison with other head-gene mutants, FI mutants are leaky, producing approx.
      0.1 phage per infected cell. Some second-site revertants of FI- phages, called
      'fin', that bypass the necessity for gpFI, have been isolated and found to
      harbour a mutation in the genes that code for the two subunits of terminase. In
      the course of mapping additional fin mutants, it was discovered that some mapped
      outside the terminase genes. To localize the mutations, restriction fragments of
      fin mutant DNAs were subcloned into plasmids and their ability to contribute to
      fin function was determined by marker-rescue analysis. The location of the fin
      mutation was further delineated by deletion analysis of a plasmid that was
      positive for fin. This showed that some fin mutations mapped to a region
      comprising genes E, D and a portion of C. The sequencing of this entire region in
      several fin isolates showed that the fin mutations are clustered in a small
      region of gene E corresponding to a portion of 26 amino acid residues of the coat
      protein (gpE). We have called this region of the protein the EFI domain. All the
      mutations result in an increase in positive charge relative to the wild-type
      protein. These results suggest that DNA maturation and packaging are in part
      controlled by an interaction between gpFI and capsid gpE.

PMID- 9159522
TI  - Modulation of the Escherichia coli sigmaE (RpoE) heat-shock transcription-factor
      activity by the RseA, RseB and RseC proteins.
AB  - The sigma(E) (RpoE) transcription factor of Escherichia coli regulates the
      expression of genes whose products are devoted to extracytoplasmic activities.
      The sigma(E) regulon is induced upon misfolding of proteins in the periplasm or
      the outer membrane. Similar to other alternative sigma factors, the activity of
      sigma(E) is tightly regulated in E. coli. We have previously shown that sigma(E)
      is positively autoregulated at the transcriptional level. DNA sequencing, coupled
      with transcriptional analyses, have shown that sigma(E) is encoded by the first
      gene of a four-gene operon. The second gene of this operon, rseA, encodes an anti
      sigma(E) activity. This was demonstrated at both the genetic and biochemical
      levels. For example, mutations in rseA constitutively increase sigma(E) activity.
      Consistent with this, overproduction of RseA leads to an inhibitory effect on
      sigma(E) activity. Topological analysis of RseA suggests the existence of one
      transmembrane domain, with the N-terminal part localized in the cytoplasm.
      Overproduction of this N-terminal domain alone was shown to inhibit sigma(E)
      activity. These observations were confirmed in vitro, because either purified
      RseA or only its purified N-terminal domain inhibited transcription from
      Esigma(E)-dependent promoters. Furthermore, RseA and sigma(E) co-purify, and can
      be co-immunoprecipitated, and chemically cross-linked. The sigma(E) activity is
      further modulated by the products of the remaining genes in this operon, rseB and
      rseC. RseB is a periplasmic protein, which negatively regulates sigma(E) activity
      and specifically interacts with the C-terminal periplasmic domain of RseA. In
      contrast, RseC is an inner membrane protein that positively modulates sigma(E)
      activity. Most of these protein-protein interactions were verified in vivo using
      the yeast two-hybrid system.

PMID- 9159523
TI  - The sigmaE-mediated response to extracytoplasmic stress in Escherichia coli is
      transduced by RseA and RseB, two negative regulators of sigmaE.
AB  - The extracytoplasmic stress response in Escherichia coli is controlled by the
      alternative sigma factor, sigma(E). sigma(E) activity is uniquely induced by the
      accumulation of outer membrane protein precursors in the periplasmic space, and
      leads to the increased production of several proteins, including the periplasmic
      protease DegP, that are thought to be required for maintaining cellular integrity
      under stress conditions. Genetic and biochemical experiments show that sigma(E)
      activity is under the control of three genes, rseABC (for regulator of sigma E),
      encoded immediately downstream of the sigma factor. Deletion of rseA leads to a
      25-fold induction of sigma(E) activity. RseA is predicted to be an inner membrane
      protein, and the purified cytoplasmic domain binds to and inhibits sigma(E)
      directed transcription in vitro, indicating that RseA acts as an anti-sigma
      factor. Deletion of rseB leads to a slight induction of sigma(E), indicating that
      RseB is also a negative regulator of sigma(E). RseB is a periplasmic protein and
      was found to co-purify with the periplasmic domain of RseA, indicating that RseB
      probably exerts negative activity on sigma(E) through RseA. Deletion of rseC, in
      contrast, has no effect on sigma(E) activity under steady-state conditions. Under
      induction conditions, strains lacking RseB and/or C show wild-type induction of
      sigma(E) activity, indicating either the presence of multiple pathways regulating
      sigma(E) activity, or the ability of RseA alone to both sense and transmit
      information to sigma(E).

PMID- 9159524
TI  - Molecular characterization of the plasmid-encoded eps gene cluster essential for
      exopolysaccharide biosynthesis in Lactococcus lactis.
AB  - Lactococcus lactis strain NIZO B40 produces an extracellular
      phosphopolysaccharide containing galactose, glucose, and rhamnose. A 40 kb
      plasmid encoding exopolysaccharide production was isolated through conjugal
      transfer of total plasmid DNA from strain NIZO B40 to the plasmid-free L. lactis
      model strain MG1614 and subsequent plasmid curing. A 12 kb region containing 14
      genes with the order epsRXABCDEFGHIJKL was identified downstream of an iso-IS982
      element. The predicted gene products of epsABCDEFGHIJK show sequence homologies
      with gene products involved in exopolysaccharide, capsular polysaccharide,
      lipopolysaccharide, or teichoic acid biosynthesis of other bacteria.
      Transcriptional analysis of the eps gene cluster revealed that the gene cluster
      is transcribed as a single 12 kb mRNA. The transcription start site of the
      promoter was mapped upstream of the first gene epsR. The involvement of epsD in
      exopolysaccharide (EPS) biosynthesis was demonstrated through a single gene
      disruption rendering an exopolysaccharide-deficient phenotype. Heterologous
      expression of epsD in Escherichia coli showed that its gene product is a
      glucosyltransferase linking the first sugar of the repeating unit to the lipid
      carrier.

PMID- 9159525
TI  - Purification and characterization of the flagellar hook-basal body complex of
      Bacillus subtilis.
AB  - The flagellar hook-basal body (HBB) complex of the Gram-positive bacterium
      Bacillus subtilis was purified and analysed by electron microscopy, gel
      electrophoresis, and amino acid sequencing of the major component proteins. The
      purified HBB complex consisted of the inner (M and S) rings, a rod and a hook.
      There were no outer (P and L) rings that are found in Gram-negative bacteria. The
      hook was 15 nm in thickness and 70 nm in length, which is thinner and longer than
      the hook of Salmonella typhimurium. The hook protein had an apparent molecular
      mass of 29 kDa, and its N-terminal sequence was identical to that of B. subtilis
      FIgG, which was previously reported as a rod protein. The sequence of the
      reported FIgG protein of B. subtilis is more closely related to that of FIgE (the
      hook protein) rather than FIgG (the rod protein) of S. typhimurium, in spite of
      the difference of the apparent molecular masses between the two hook proteins (29
      kDa versus 42 kDa). The hook-basal body contained six major proteins (with
      apparent molecular masses of 82, 59, 35, 32, 29 and 20 kDa) and two minor
      proteins (23 kDa and 13 kDa), which consistently appeared from preparation to
      preparation. The N-terminus of each of these proteins was sequenced. Comparison
      with protein databases revealed the following polypeptide-gene correspondences:
      82 kDa, fIiF; 59 kDa, fIgK; 35 kDa, orfF; 32 kDa, yqhF; 23 kDa, orf3 of the fIaA
      locus; 20 kDa, fIgB and fIgC; 13 kDa, not determined. The band at 20 kDa was a
      mixture of FIgB and FIgC, as revealed by two-dimensional gel analysis.
      Characteristic features of B. subtilis HBB are discussed in comparison with those
      of S. typhimiurium.

PMID- 9159526
TI  - Microbial pathogenesis in cystic fibrosis: co-ordinate regulation of heat-shock
      response and conversion to mucoidy in Pseudomonas aeruginosa.
AB  - Conversion of Pseudomonas aeruginosa to the mucoid phenotype plays a major role
      in the pathogenesis of respiratory infections in cystic fibrosis (CF). One
      mechanism responsible for mucoidy is based on mutations that inactivate the anti
      sigma factor, MucA, which normally inhibits the alternative sigma factor, AIgU.
      The loss of MucA allows AIgU to freely direct transcription of the genes
      responsible for the production of the exopolysaccharide alginate resulting in
      mucoid colony morphology. In Escherichia coli, a close homologue of AIgU,
      sigma(E), directs transcription of several genes under conditions of extreme heat
      shock. Here we examined whether AIgU, besides its role in controlling alginate
      production, affects the heat-shock response in P. aeruginosa. The P. aeruginosa
      rpoH gene encoding a homologue of the major heat-shock sigma factor, sigma32, was
      found to be transcribed by AIgU containing RNA polymerase from one of its
      promoters (P3) identified in this study. Transcription of rpoH from P3 was
      elevated upon exposure to extreme heat shock in an aIgU-dependent manner.
      Importantly, the AIgU-dependent promoter of rpoH was found to be activated in
      mucoid mucA mutants. In keeping with this observation, introduction of a wild
      type mucA gene abrogated AIgU-dependent rpoH transcription in mucoid P.
      aeruginosa laboratory isolates and CF isolates. These results suggest that
      conversion to mucoidy and the heat-shock response are co-ordinately regulated in
      P. aeruginosa. The simultaneous activation of both systems in mucA mutants,
      selected in the lungs of CF patients, may have significance for the inflammatory
      processes characteristic of the establishment of chronic infection and ensuing
      clinical deterioration in CF.

PMID- 9159527
TI  - Host-cell cyclophilin is important for the intracellular replication of
      Leishmania major.
AB  - The antiparasitic effects of cyclosporin A were examined in leishmanial infection
      by analysing the role of CsA-binding proteins (cyclophilins) in the host-parasite
      interaction. We hypothesized that the leishmanicidal effects of CsA on Leishmania
      major infected macrophages might be mediated through a cyclophilin of either the
      parasite or the host cell. Two cyclophilins (20 and 22 kDa) were purified from L.
      major parasites and N-terminally sequenced. Although enzyme activity of these
      cyclophilins was inhibited by CsA, pretreatment of L. major parasites with CsA
      did not result in reduction of a subsequent macrophage infection, arguing against
      a role of L. major cyclophilins as infectivity potentiators. However, host-cell
      cyclophilin A (CypA) was found to be critically involved in the intracellular
      replication of L. major parasites in murine macrophages. An antisense
      oligonucleotide to murine CypA was constructed and added to cultures of
      peritoneal macrophages prior to infection with L. major parasites. This treatment
      strongly reduced the expression of CypA in macrophages and resulted in the
      inhibition of the intracellular replication of L. major amastigotes. These data
      indicate that interaction of amastigotes with host-cell cyclophilin is an
      important part of the intracellular replication machinery of L. major and define,
      for the first time, a direct involvement of a cyclophilin in the survival
      strategies of an intracellular parasite.

PMID- 9159528
TI  - Aminoglycoside 2'-N-acetyltransferase genes are universally present in
      mycobacteria: characterization of the aac(2')-Ic gene from Mycobacterium
      tuberculosis and the aac(2')-Id gene from Mycobacterium smegmatis.
AB  - The genus Mycobacterium comprises clinically important pathogens such as M.
      tuberculosis, which has reemerged as a major cause of morbidity and mortality
      world-wide especially with the emergence of multidrug-resistant strains. The use
      of fast-growing species such as Mycobacterium smegmatis has allowed important
      advances to be made in the field of mycobacterial genetics and in the study of
      the mechanisms of resistance in mycobacteria. The isolation of an aminoglycoside
      resistance gene from Mycobacterium fortuitum has recently been described. The
      aac(2')-Ib gene is chromosomally encoded and is present in all isolates of M.
      fortuitum. The presence of this gene in other mycobacterial species is studied
      here and genes homologous to that of M. fortuitum have been found in all
      mycobacterial species studied. In this report, the cloning of the aac(2')-Ic gene
      from M. tuberculosis H37Rv and the aac(2')-Id gene from M. smegmatis mc(2)155 is
      described. Southern blot hybridizations have shown that both genes are present in
      all strains of this species studied to date. In addition, the putative aac(2')-Ie
      gene has been located in a recent release of the Mycobacterium leprae genome. The
      expression of the aac(2')-Ic and aac(2')-Id genes has been studied in M.
      smegmatis and only aac(2')-Id is correlated with aminoglycoside resistance. In
      order to elucidate the role of the aminoglycoside 2'-N-acetyltransferase genes in
      mycobacteria and to determine whether they are silent resistance genes or whether
      they have a secondary role in mycobacterial metabolism, the aac(2')-Id gene from
      M. smegmatis has been disrupted in the chromosome of M. smegmatis mc(2)155. The
      disruptant shows an increase in aminoglycoside susceptibility along with a slight
      increase in the susceptibility to lysozyme.

PMID- 9159529
TI  - Sequence analysis of an exceptionally conserved operon suggests enzymes for a new
      link between histidine and purine biosynthesis.

PMID- 9159530
TI  - Therapy for psoriatic arthritis: sometimes a conflict for psoriasis.

PMID- 9159531
TI  - The expanding role of the nurse in rheumatology.

PMID- 9159532
TI  - Enhanced co-stimulatory ability of synovial fluid accessory cells in rheumatoid
      arthritis.
AB  - We have established in vitro assays that allow the examination of co-stimulatory
      function of rheumatoid arthritis (RA) antigen-presenting cells (APC). Synovial
      fluid (SF) and peripheral blood (PB) APC co-stimulatory ability was compared in
      the activation of peptide-specific human T-cell clones. T-cell receptor (TCR)
      stimulation by peptide or anti-CD3 antibody allowed the direct comparison of SF
      and PB APC co-stimulatory activity, separately from their ability to process
      antigen. SF APC from 15 RA patients consistently enhanced T-cell proliferation
      when compared to their PB counterparts. Moreover, increasing the numbers of PB
      APC present resulted in only a minor increase in T-cell proliferation, failing to
      achieve levels stimulated by SF APC. We propose that the enhanced co-stimulatory
      function of synovial APC may be a significant factor in the persistence of local
      immune responses in RA.

PMID- 9159533
TI  - Immunocytochemical analysis of tissue kallikrein and the kinin moiety in
      rheumatoid synovial fluid neutrophils.
AB  - Polymorphonuclear leucocytes (PMNs) from the synovial fluid of patients with
      rheumatoid arthritis (RA) showed reduced tissue kallikrein and kinin
      immunoreactivity in comparison with blood PMNs from healthy individuals as judged
      visually using confocal microscopy. Similarly, synovial fluid PMNs exhibited
      reduced tissue kallikrein immunoreactivity as compared with blood PMNs from the
      same RA patients. Blood PMNs stimulated to degranulate in vitro also displayed
      less immunostaining for tissue kallikrein and kinin than non-stimulated PMNs. By
      contrast, no difference in kininogen immunostaining was detected between RA
      synovial fluid PMNs and blood PMNs from healthy people. It is considered that the
      results support the hypothesis that tissue kallikrein, released from the granules
      of RA synovial fluid PMNs, cleaves the kinin moiety from multifunctional
      kininogen protein on the surface of the PMNs.

PMID- 9159534
TI  - High prolactin and low dehydroepiandrosterone sulphate serum levels in patients
      with severe systemic sclerosis.
AB  - The aim was to determine serum levels of prolactin (PRL) and
      dehydroepiandrosterone sulphate (DHEAS), and to demonstrate a link between PRL or
      DHEAS and soluble immune mediators in patients with systemic sclerosis (SSc) with
      different degrees of disease-induced organ involvement. Thirty-one patients with
      SSc were studied to evaluate 18 possible disease manifestations. In the serum,
      PRL, DHEAS and soluble immune mediators were determined by ELISA. Compared to SSc
      with <9 disease manifestations, patients with > or =9 disease manifestations had
      higher PRL (P = 0.044), higher soluble interleukin 2 receptor (sIL-2R, P = 0.004)
      and vascular cell adhesion molecule (sVCAM, P = 0.044), and lower DHEAS (P =
      0.029). PRL (R(Rank) = 0.490, P = 0.003) and DHEAS (R(Rank) = -0.399, P = 0.013)
      were significantly correlated with the number of disease manifestations. The
      inverse correlation between PRL and DHEAS showed a trend (P = 0.059). PRL
      correlated with sIL-2R (R(Rank) = 0.553, P = 0.001) and sVCAM (R(Rank) = 0.520, P
      = 0.002). The number of disease manifestations and sIL-2R correlated
      significantly (R(Rank) = 0.463, P = 0.006). Psychometric variables to examine the
      presence of depression were not measured, but from the general aspect, the
      patients were not suffering from major depression which may have influenced our
      results. In conclusion, this study demonstrates the close association between
      DHEAS and, particularly, PRL and SSc severity and T-lymphocyte mechanisms.

PMID- 9159535
TI  - Testosterone metabolism and cyclosporin A treatment in rheumatoid arthritis.
AB  - A constant dose-dependent side-effect in cyclosporin A (CSA)-treated patients is
      the appearance of hypertrichosis; this occurs in both sexes and suggests an
      androgenizing activity. To determine the influence of CSA on peripheral androgen
      metabolism, we evaluated in rheumatoid arthritis (RA) patients treated with low
      dose CSA (3.5 mg/kg/day), during a period of 12 months, plasma levels of
      testosterone (Tes) and of 5alpha-androstane-3alpha, 17beta-diol glucuronide
      (Adiol-G), an important peripheral Tes metabolite. Clinical and laboratory
      parameters of RA were also monitored. Furthermore, the metabolism of
      physiological concentrations of Tes (1 x 10(-8) M) was evaluated in primary
      cultures of RA synovial macrophages (M phi) in the presence of CSA concentrations
      close to the pharmacological immunosuppressive doses (100-500 ng/ml). At the
      final time of observation (12 months), a significant increase in the mean plasma
      Adiol-G level was observed in patients of both sexes. The increase was evident
      after 1 month of treatment in male patients (P < 0.01) and after 3 months in
      female patients (P < 0.05). Almost all the patients experienced the side-effect
      of a low-degree hypertrichosis after a mean period of 1-2 months. No significant
      correlations with the laboratory parameters of the disease were observed. Results
      from in vitro experiments on Tes metabolism by cultured synovial M phi showed at
      24 and 48 h, in the presence of CSA, a significantly (P < 0.0001) greater
      formation of dihydrotestosterone and increased amounts of other Tes metabolites,
      including androstenedione, androsterone and epiandrosterone, when compared to
      untreated controls. In conclusion, the appearance of a dose-related
      hypertrichosis and the increase in plasma androgen metabolites (i.e. Adiol-G) in
      CSA-treated patients, as well as the hormonal metabolic effects on cultured
      synovial M phi, should be regarded as possible markers of the influence of CSA on
      peripheral androgen metabolism at the level of target cells.

PMID- 9159536
TI  - The impact of HLA-DRB1*0405 on disease severity in Korean patients with
      seropositive rheumatoid arthritis.
AB  - Many reports have described HLA-DRB1 genes as having an influence on disease
      severity and susceptibility in rheumatoid arthritis (RA). Studies were undertaken
      to define the effect of RA-associated alleles on disease severity in Korean
      patients with seropositive RA. The results indicate that the most common RA
      susceptibility allele, HLA-DRB1*0405, is significantly associated with bony
      erosion, joint deformity and extra-articular manifestations. However, RA
      associated alleles in Koreans have less effect on nodular disease than in
      Caucasians. This suggests that the presence of RA-associated alleles, especially
      HLA-DRB1*0405, seems to be a prognostic marker for severe erosive disease in
      Koreans.

PMID- 9159537
TI  - Body composition in rheumatoid arthritis.
AB  - The objectives were to assess bone mineral density (BMD) at different body sites
      in rheumatoid arthritis (RA) patients related to disease severity parameters,
      disease duration and corticosteroid intake, and to look for body composition
      measurements as lean body mass (LBM) and per cent fat as possible prognostic
      factors in RA. Body composition values were measured cross-sectionally in 89 RA
      patients and compared with 157 controls. Patients were divided into males and
      postmenopausal females, ever steroid treated and never steroid treated. BMD
      values of all body sites were significantly lower compared to normals in all
      subgroups, except for the lumbar spine (L2 L4) in all postmenopausal women and
      males never treated with steroids. There was also no clear BMD decrease in the
      arms of male RA patients. LBM was significantly lower in all body parts compared
      to controls, whereas the fat distribution ratio (FDR) showed a clear shift to
      abdominal in all patients. These are parameters of chronic illness and a
      predictor of cardiovascular disease, respectively. BMD data confirm our previous
      data in different patient groups (low at appendicular sites, normal lumbar BMD),
      but no clear influence of disease severity and steroid intake could be found.
      Body composition data, as LBM and FDR, are also altered in RA patients: decreased
      LMB and more central FDR. Their usefulness as prognostic markers in early RA
      patients needs to be clarified prospectively in these patient groups.

PMID- 9159538
TI  - Seasonal variations in manifestations and activity of systemic lupus
      erythematosus.
AB  - The purpose of the present study was to investigate a possible seasonal pattern
      in various clinical and laboratory manifestations in a group of systemic lupus
      erythamatosus (SLE) patients. One hundred and five SLE patients were followed up
      during a 4 yr period. Data on each of the clinical and laboratory variables
      examined, as well as the results of the disease activity index (SLEDAI), were
      plotted against the month during which they were obtained. Photosensitivity was
      the only variable to show a seasonal pattern, having higher scores during the
      summer months (1.04 +/- 0.16 in July vs 0.58 +/- 0.12 in December). We were
      unable to show seasonal patterns in any of the other variables examined. As a
      group, SLE patients do not show any significant seasonal pattern in disease
      manifestations and activity, except for photosensitivity. However, such a pattern
      may exist for the individual patient.

PMID- 9159539
TI  - A comparison of two nomenclature systems for primary systemic vasculitis.
AB  - Recently, two new systems have been proposed for the nomenclature of primary
      vasculitides: the 1990 American College of Rheumatology (ACR) classification
      criteria and the 1992 Chapel Hill Consensus Conference (CHCC) definitions. We
      compared these two systems in the same cohort of patients with primary systemic
      vasculitis. Twenty-four patients were studied and, applying the 1990 ACR
      criteria, the diagnoses were Wegener's granulomatosis (WG) (15), Churg Strauss
      syndrome (CSS) (4), polyarteritis nodosa (PAN) (2) and unclassified (3). Using
      the CHCC definitions, the diagnoses were WG (5), microscopic polyangiitis (MPA)
      (8), possible MPA (1), PAN (1) and undefined (9). There was concordance in only
      five patients (all WG). Significant discordance exists between these two criteria
      sets. Since the ACR criteria set does not include MPA, WG tends to be
      overdiagnosed. The Chapel Hill definitions are biopsy dependent and surrogate
      features for the defining histology are required to allow their practical
      application.

PMID- 9159540
TI  - Clinical and echocardiographic survey of the Ehlers-Danlos syndrome.
AB  - Cardiac abnormalities such as mitral valve prolapse (MVP) are reported to be
      common features of the Ehlers Danlos syndrome (EDS), and it has been suggested
      that the majority of patients with type IV EDS will have cardiac involvement and
      vascular aneurysms. However, the evidence for valve lesions is inconsistent and
      often based on early clinical studies using mainly M-mode echo. We studied 33
      patients (six male, 27 female; median age 35 yr) with EDS (30 type I, II or III,
      three type IV) and 30 age- and sex-matched controls. The study assessed skin
      stretch and joint hypermobility using Beighton and Contompasis scores.
      Echocardiographic examination included standard two-dimensional views from the
      parasternal and apical windows, and measurement of the aorta at four sites
      (annulus, sinotubular junction, arch and abdominal aorta). Echocardiographic
      abnormalities were found in four patients (12.1%) (one atrial septal aneurysm,
      one tricuspid prolapse, two MVP) and two controls (6.7%). MVP was found in 6.1%
      of EDS patients and 7% of controls. Seven patients had previously been diagnosed
      as having MVP; only two were shown to have true MVP using current criteria. None
      of those with type IV EDS had any echocardiographic abnormality. No patients with
      EDS had mean aortic dimensions outside the normal range at any of the points
      tested. Cardiac symptoms were more frequent amongst the patients than controls
      (atypical chest pain 48%, P = 0.0001; palpitation 39%, P = 0.001; exertional
      dyspnoea 30%). A wide range of rheumatological complaints were reported (current
      arthralgia 75%; recent back pain 72%, P = 0.005; recurrent dislocation 72%).
      Contrary to earlier published observations, we have not found an increased
      incidence of cardiac abnormalities in EDS. This syndrome may be relatively more
      benign, from the cardiac point of view, than was previously thought.

PMID- 9159541
TI  - Use of the short form 36 (SF36) for health status measurement in rheumatoid
      arthritis.
AB  - The patient-administered Health Assessment Questionnaire (HAQ) is widely used in
      rheumatology studies. Another health quality assessment technique commonly used
      for other non-rheumatological conditions is the 'Short Form 36' (SF36). This has
      questions designed to assess eight aspects of health ranging from physical
      limitations to general perceptions of vitality and mental well-being. This study
      presents information on the health status of 137 patients with rheumatoid
      arthritis (RA) assessed by both the SF36 and HAQ. Summary statistics are given
      for the elements of the SF36 according to age, gender, disease measures of RA and
      the presence of co-morbidity. There were significant associations between the
      physical functioning score of the SF36 and the HAQ score. with other measures of
      disease activity and severity, and with co-morbidity, although there was
      considerable inter-patient variability. These findings suggest that future
      applications of health status questionnaires are possible.

PMID- 9159542
TI  - Are rheumatoid arthritis patients more willing to accept non-steroidal anti
      inflammatory drug treatment risks than osteoarthritis patients?
AB  - One hundred and thirty-four patients with either osteoarthritis or rheumatoid
      arthritis, and with a history of current or past non-steroidal anti-inflammatory
      drug (NSAID) treatment, were interviewed regarding the benefits, expectations and
      side-effects of NSAID therapy. Their willingness to accept risks in medical
      treatment was also evaluated. Both groups experienced positive effects of the
      NSAID treatment corresponding to their expectations. However, rheumatoid
      arthritis patients were significantly more willing to accept gastrointestinal
      side-effects when given an effective NSAID than the osteoarthritis patients, and
      they were also more willing to take risks in trying a hypothetical new NSAID that
      had been shown to be effective in clinical trials.

PMID- 9159543
TI  - Management of oral complications of disease-modifying drugs in rheumatoid
      arthritis.
AB  - Stomatitis is a troublesome adverse effect of disease-modifying anti-rheumatic
      drug (DMARD) therapy in rheumatoid arthritis (RA) patients. This review presents
      data to examine the incidence, clinical features and consequences of DMARD
      related stomatitis, and suggests an algorithm for its clinical management. The
      specific objectives of the two studies presented here were to determine the
      incidence of DMARD-related stomatitis and its effect on DMARD continuation, and
      secondly to identify the clinical and laboratory risk factors. We investigated
      two cohorts of patients: (i) a retrospective survey of data collected from drug
      monitoring clinics run for patients on DMARDs from 1987 to 1994 involving 1539
      patients and 2394 drug exposures; (ii) a prospective study of 25 consecutive RA
      patients presenting with DMARD-related stomatitis compared to 29 RA controls with
      no history of DMARD stomatitis. The retrospective survey showed that 2% of DMARD
      patients stopped therapy because of stomatitis, but 55% of these were able to
      resume the same therapy. In the case control study. 24% of patients discontinued
      temporarily and 8% permanently. Cases of DMARD-related stomatitis differed from
      controls in that they had a higher incidence of previous mouth ulcers (40% vs
      14%), they smoked less (8% vs 31%) and Schirmer's test was more often abnormal
      (44% vs 21%). There were no differences in RA severity, disease activity or oral
      hygiene. Haematinic deficiencies were equally common in cases and controls: 30%
      for iron, 8% for vitamin B12 and 24% for folic acid. Herpes simplex virus was
      involved in a minority (8%) of cases. In conclusion, the occurrence of stomatitis
      in RA patients on DMARD should not lead to cessation of drug therapy, but to a
      careful evaluation so that patients may be maintained on effective treatment.

PMID- 9159544
TI  - Rheumatology in Singapore.

PMID- 9159545
TI  - Rheumatology out-patient workload increases inexorably.
AB  - Rheumatology out-patient consultations in the south-west of England from 1 to 30
      November 1994 were recorded by standard methods and compared to 1988, 1990, 1991
      and 1992. Historical records at one centre provided additional detailed
      information. There has been an overall increase of 31% in the number of patients
      seen (30% for follow-up cases, 36% for new referrals), but the mean waiting time
      for new patient consultations increased from 65 to 108 days. The proportion of
      new patient consultations with non-arthritic diseases increased by 8.2%, and
      those with rheumatoid arthritis and polyarthritis decreased by 9.0%. Variation in
      discharge rates and length of follow-up appointments occurred, but mostly in
      uncommon diagnostic categories. Referral rates have been rising faster since the
      introduction of National Health Service reforms than can be accommodated by the
      increased workload undertaken.

PMID- 9159546
TI  - Anti-rheumatic drug-prescribing behaviour of Australasian rheumatologists 1984
      1994.
AB  - The prescribing behaviour of Australian and New Zealand rheumatologists was
      studied in 1994 using a questionnaire, and the results compared with a similar
      questionnaire administered in 1984. Perceived differences in efficacy and
      toxicity for disease-modifying anti-rheumatic drugs (DMARDs) and cytotoxics were
      reported. Over the decade, methotrexate and sulphasalazine have become the most
      commonly used anti-rheumatic agents, and methotrexate is clearly seen as the most
      effective drug. Wide variations in monitoring practices for DMARDs were reported,
      highlighting the need for cost-effectiveness studies on monitoring. There was low
      usage of functional outcome measurements in assessing patients.

PMID- 9159547
TI  - Antibodies against bacterial lipopolysaccharides in Japanese patients with
      ankylosing spondylitis.
AB  - We investigated IgG, IgA and IgM class specific antibodies to five bacterial
      (Klebsiella pneumoniae, Escherichia coli, Salmonella enteritidis, Salmonella
      typhimurium and Shigella flexneri) lipopolysaccharides (LPS) by enzyme-linked
      immunosorbent assay in 144 Japanese patients with ankylosing spondylitis (AS). AS
      patients had significantly elevated IgA antibodies to K. pneumoniae LPS,
      Salmonella enteritidis LPS and Salmonella typhimurium LPS; however, there was no
      correlation between antibody level to LPS and acute-phase reactants, erythrocyte
      sedimentation rate and serum C-reactive protein.

PMID- 9159548
TI  - Erosive amyloidosis of the wrist and knee associated with oligoclonal bands.
AB  - We report on a patient who presented with an inflammatory arthropathy clinically,
      though without a raised erythrocyte sedimentation rate, and in whom investigation
      subsequently showed erosive amyloidosis with an oligoclonal band. There was no
      evidence of rheumatoid disease and she has not developed any haematological
      malignancy. The only other case reported in the literature had an elevated
      erythrocyte sedimentation rate and went on to develop a lymphoplasmacytoid
      lymphoma.

PMID- 9159549
TI  - Behcet's syndrome progressing to gastrointestinal perforation in a West African
      male.

PMID- 9159550
TI  - Case history of a patient with multiple sclerosis and scleroderma.

PMID- 9159551
TI  - Three year follow-up of a case of giant cell arteritis presenting with a chronic
      cough and upper limb ischaemic symptoms.

PMID- 9159552
TI  - Hypersensitivity vasculitis related to aceclofenac.

PMID- 9159553
TI  - Synovitis associated with an electrical injury.

PMID- 9159554
TI  - Has hepatitis C virus a specific tropism for the synovial membrane?

PMID- 9159555
TI  - Does application of radiographic contrast medium in radiation synovectomy
      influence the stability of Yttrium-90 colloid?

PMID- 9159556
TI  - Rheumatology in Israel.

PMID- 9159557
TI  - Erythrocyte sedimentation rate (ESR) at presentation is a prognostic indicator
      for duration of treatment in polymyalgia rheumatica (PMR)

PMID- 9159558
TI  - Pharmacoeconomics: evaluating the evaluators.

PMID- 9159559
TI  - Population pharmacokinetics of lamotrigine monotherapy in patients with epilepsy:
      retrospective analysis of routine monitoring data.
AB  - AIMS: To examine the population pharmacokinetics of lamotrigine in patients newly
      diagnosed with epilepsy and receiving oral lamotrigine monotherapy for up to 48
      weeks. METHODS: The population consisted of 158 Caucasians and 5 Asians of whom
      81 were males and 82 females. Age and weight ranged between 14 and 76 years and
      41-107 kg, respectively. A one-compartment compartment model with first-order
      absorption and elimination was fitted to plasma lamotrigine concentration-time
      profiles from retrospective drug monitoring, using non-linear mixed effect
      modelling (NONMEM), with first-order estimation. Oral clearance (CLo), apparent
      volume of distribution (V/F) and absorption rate constant (Ka) were the main
      pharmacokinetic parameters. RESULTS: CLo was not significantly influenced by body
      weight, age, gender, oral contraceptives and dose. However, due to auto-induction
      CLo increased by 17.3% during the 48 weeks of therapy, from 1.94 to 2.28 l h(-1),
      and was 28.7% lower in Asians than Caucasian. The final magnitude in interpatient
      variability was 32%. The effect of the covariates weight, age, race and gender on
      V/F was examined and none was statistically significant. The final population
      estimate of V/F was 77.4 l with an interpatient variability of 34%. CONCLUSIONS:
      In view of the wide therapeutic margin of lamotrigine and the 21% residual
      variability in plasma concentrations, the modest significant effects of race and
      auto-induction on clearance are unlikely to be clinically significant and, thus,
      no dosage adjustment is warranted for these effects.

PMID- 9159560
TI  - Lack of inhibitory effect of cimetidine on caffeine metabolism in children using
      the caffeine breath test.
AB  - AIMS: To study the potential drug interaction between cimetidine and caffeine in
      a group of children who received cimetidine for gastritis. METHODS: The caffeine
      breath test was carried out prior to the administration of cimetidine and after 2
      3 weeks therapy. The children (n = 1) received 300-800 mg cimetidine daily (11-36
      mg kg(-1) day(-1)). RESULTS: There was no significant change in the 2 h
      cumulative labelled CO2 following the administration of cimetidine (mean values
      5.61% before and 4.87% during cimetidine; Student's t-test P > 0.2). CONCLUSIONS:
      Cimetidine did not have an inhibitory effect on the metabolism of caffeine in
      this group of children studied.

PMID- 9159562
TI  - Pharmacokinetic and pharmacodynamic interaction trial after repeated oral doses
      of imidapril and digoxin in healthy volunteers.
AB  - AIMS: To investigate the potential pharmacokinetic and pharmacodynamic
      interaction between imidapril and digoxin. METHODS: AUC, Cmax and t(max) of
      imidapril, imidaprilat and digoxin were calculated and evaluated in a randomized,
      doubleblind three-period cross-over design in 12 healthy volunteers after 8 days
      treatment with the following combinations: digoxin 0.25 mg day(-1) + placebo (D +
      P); imidapril 10 mg day(-1) + placebo (I + P); imidapril 10 mg day)(-1) + digoxin
      0.25 mg day(-1) (I + D). RESULTS: Mean AUC (0, 24 h) of digoxin was 10.4 (+/- 4.9
      s.d.) ng ml(-1) h (D + P) and 10.7 (+/- 3.9 s.d.) ng ml(-1) h (I + D),
      respectively (90%-confidence intervals [CI] for the ratio of (D + P) and (I + D):
      0.91-1.27, point estimator [PE]: 1.06). Mean AUC (0, 24 h) of imidapril was 133
      (+/- 86 s.d.) ng ml(-1) h (I + P) and 108 (+/- 52 s.d.) ng ml(-1) h (I + D),
      respectively (90%-CI: 0.76-0.94, PE 0.85). AUC (0, 24 h) of imidaprilat was 215
      (+/- 91 s.d.) ng ml(-1) h (I + P) and 194 (+/- 54 s.d.) ng ml(-1) h (I + D),
      respectively (90%-CI: 0.80-1.08, PE 0.93). Cmax was 19.9 (+/- 8.7 s.d.) ng ml(-1)
      (I + P) and 15.9 (+/- 5.3 s.d.) ng ml(-1) (I + D) (90%-CI: 0.67-1.00, PE 0.82).
      The results indicate a slight reduction of imidapril and imidaprilat plasma
      levels when coadministered with digoxin without any effect on digoxin plasma
      levels. Maximal ACE-inhibition was 79% (I + P) and 67% (I + D). CONCLUSIONS:
      Grouped data analysis of imidaprilat plasma levels vs ACE-activity showed that
      for maximal inhibition of plasma ACE activity, imidaprilat plasma levels should
      exceed 10 ng ml(-1). Under digoxin and imidapril, more plasma concentrations of
      imidaprilat were seen under this level as after imidapril alone, this reduces the
      integral of the ACE-inhibition/time curves by about 20 to 30%.

PMID- 9159561
TI  - Concentrations and effects of zopiclone are greatly reduced by rifampicin.
AB  - AIMS: The effects of rifampicin on the pharmacokinetics and pharmacodynamics of
      zopiclone, a non-benzodiazepine hypnotic, were studied. METHODS: In a randomized,
      placebo-controlled cross-over study with two phases, eight young healthy
      volunteers took either 600 mg rifampicin or placebo once daily for 5 days. On the
      6th day, 10 mg zopiclone was administered orally. Plasma zopiclone concentrations
      and effects of zopiclone were measured for 10 h. RESULTS: The total area under
      the plasma zopiclone concentration-time curve after rifampicin was 18.0% (95% CI
      13.5-22.5%) of that after placebo (86.1 +/- 34.5 ng ml(-1) h vs 473 +/- 114 ng
      ml(-1) h (mean +/- s.d.); P<0.001). Rifampicin decreased the peak plasma
      concentration of zopiclone from 76.9 +/- 27.2 ng ml(-1) to 22.5 +/- 6.0 ng ml(-1)
      (P<0.001) and the half-life from 3.8 +/- 0.6 h to 2.3 +/- 0.9 h (P<0.005). A
      significant (P<0.02) reduction in the effects of zopiclone was seen in three of
      the five psychomotor tests used (digit symbol substitution test, critical flicker
      fusion test and Maddox wing test) after rifampicin pretreatment. CONCLUSIONS: The
      strong interaction of rifampicin with zopiclone is due to enhanced metabolism of
      zopiclone. Zopiclone may show a reduced hypnotic effect when used concomitantly
      with rifampicin or other potent inducers of CYP3A4 such as phenytoin and
      carbamazepine.

PMID- 9159563
TI  - Natriuretic efficiency of frusemide as a consequence of drug input rate.
AB  - AIMS: The aim of the present study was to investigate the influence of the rate
      of delivery of frusemide to its site of action on the effect and efficiency of
      the drug. METHODS: Frusemide 30 mg was administered as a bolus dose, a slow-rate
      infusion and a bolus dose in combination with 2 g of probenecid in a three way
      cross-over design to seven healthy volunteers. Urinary volume and contents of
      frusemide and sodium were measured in samples collected over 10 h. RESULTS: Total
      natriuretic response was 40% higher (P < 0.001) after the infusion and 20% higher
      (P < 0.05) after the combined treatment with probenecid, as compared with the
      bolus dose. Total natriuretic efficiency did not differ between the infusion
      (0.013 mmol microg(-1)) and the combined treatment with probenecid (0.015 mmol
      microg(-1)), but was significantly higher as compared with the bolus dose (0.009
      mmol microg(-1)). Natriuretic effect data were modeled according to the sigmoid
      Emax model and the frusemide excretion rate with maximum efficiency (ER(effmax))
      was calculated from the estimated parameters. For both the frusemide infusion and
      the combined treatment with probenecid, the time course of delivery of frusemide
      into the urine consistently approached ER(effmax) more closely than was the case
      for the bolus dose. The natriuretic effect vs frusemide excretion rate curves
      were shifted to the right, and the estimated values of the sigmoid Emax model
      were higher for EC50 and lower for the slope factor after the bolus dose, which
      may indicate tolerance development for this treatment. CONCLUSIONS: Slowing the
      delivery of frusemide to the site of action increased the efficiency of the drug,
      leading to an increased natriuretic response.

PMID- 9159564
TI  - Intra-arterial substance P mediated vasodilatation in the human forearm:
      pharmacology, reproducibility and tolerability.
AB  - AIMS: The current studies were designed to characterize the pharmacology,
      reproducibility and tolerability of the vasodilator response to intra-arterial
      substance P infusion in the forearm of healthy man. METHODS: On different
      occasions, eight healthy male volunteers received brachial artery infusions of
      substance P at doubling doses ranging from 0.5 to 128 pmol min(-1). Blood flow
      was measured in both arms using venous occlusion plethysmography. RESULTS:
      Substance P induced dose-dependent vasodilatation in the human forearm which had
      a log-linear relationship to dose. At doses of 1-8 pmol min(-1), mean responses
      were highly reproducible both within and between days. There were no differences
      between responses to discontinuous doses and continuous doses of substance P.
      Substance P was generally well tolerated at doses of < or = 64 pmol min(-1) with
      no significant alteration in arterial blood pressure or heart rate. Skin oedema
      in the infused forearm and systemic vasodilatation, manifested by facial flushing
      and non-infused forearm vasodilatation, occurred at doses of > or = 16 pmol min(
      1). CONCLUSIONS: Forearm vasodilatation to substance P represents a reproducible
      and useful model in the assessment of peripheral endothelial cell NK1 receptor
      function.

PMID- 9159566
TI  - Dopamine natriuresis in salt-repleted, water-loaded humans: a dose-response
      study.
AB  - AIMS: The purpose of the present study was to define the dose-response
      relationship between exogenous dopamine and systemic haemodynamics, renal
      haemodynamics, and renal excretory function at infusion rates in the range 0 to
      12.5 microg kg(-1) min(-1) in normal volunteers. METHODS: While undergoing water
      diuresis, eight subjects were infused with 0, 1, 2, 3, 5, 7.5, 10 or 12.5 microg
      of dopamine kg(-1) min(-1) over 2 h in a randomized and double-blind fashion. On
      each study day, renal clearance studies were performed during a 1 h baseline
      period and subsequently during the second 1 h infusion period. Lithium clearance
      (CL(Li)) was used to estimate proximal tubular outflow. RESULTS: Cardiac output
      increased with the four highest doses. Mean arterial pressure followed a biphasic
      pattern with a decrease during the two lowest doses and a dose-dependent increase
      from the 7.5 microg kg(-1) min(-1) dose onwards. Effective renal plasma flow
      increased with all doses of dopamine, but peaked with the 3 microg kg(-1) min(-1)
      infusion rate [from 617 (585-649) ml min(-1) with placebo to 915 (824-1006) ml
      min(-1) (means with 95% CI, P<0.001)]. None of the doses changed glomerular
      filtration rate (GFR). Sodium clearance (CL(Na)) and CL(Li) were elevated with
      the four lowest doses but increased further from 7.5 microg kg(-1) min(-1)
      onwards. Compared with placebo, the percentage increase in CL(Na) with increasing
      dose was 77 (5-159), 93 (13-172), 107 (24-190), 121 (60-181), 253 (65-441), 284
      (74-494), and 212 (111-312) %, respectively. There were only small, inconsistent
      decreases in absolute proximal reabsorption rate (APR = GFR-CL(Li)). Fractional
      distal reabsorption of sodium (FDR(Na) = (CL(Li)-CL(Na))/CL(Li)) decreased with
      all doses, reaching its nadir with 7.5 microg kg(-1) min(-1) [from 95.9 (94.6
      97.2) % with placebo to 91.5 (90.0-93.0) % (P<0.01)] whereafter a flat dose
      response curve was observed. CONCLUSIONS: In conclusion, the renal vasodilating
      effect of dopamine was maximal with 3 microg kg(-1) min(-1). The dose-dependent
      attenuation seen with higher doses is consistent with an increased alpha
      adrenergic stimulation opposing the effect on dopaminergic receptors. The present
      CL(Li) studies confirm that dopamine increases proximal tubular outflow. The
      results suggest that the natriuretic effect of depressor doses of dopamine was
      primarily caused by attenuation of the increase in distal sodium reabsorption
      normally seen after an increase in proximal tubular outflow. Pressor doses
      further increased sodium excretion, indicating the presence of pressure
      natriuresis at these high doses.

PMID- 9159565
TI  - Characterization of angiotensin-II effects on cerebral and ocular circulation by
      noninvasive methods.
AB  - AIMS: The role of the renin-angiotensin-system (RAS) in the cerebral and ocular
      circulation is still a matter of controversy. In vitro and animal data lead to
      partially contradicting results. However, direct investigation of locally
      generated angiotensin II (Ang II) in humans is not possible in vivo. Hence, we
      hypothesised that it might be possible to characterize local effects of Ang II by
      comparing systemic and local haemodynamic parameters during exogenous Ang II
      infusion. METHODS: In a placebo-controlled, double-blind, two-way cross over
      study blood flow velocities in the middle cerebral and the ophthalmic artery and
      ocular fundus pulsations were measured during stepwise increasing doses of Ang II
      in 10 healthy subjects. Blood flow velocities were assessed by Doppler
      sonography, fundus pulsation amplitudes (FPA), which estimate local pulsatile
      ocular blood flow were measured by laser interferometry. Additionally, systemic
      blood pressure and pulse rate were measured. RESULTS: Ang II dose-dependently
      decreased resistive index (RI) and increased mean flow velocities (MFV) in both
      arteries. Fundus pulsation amplitude was dose-dependently decreased by Ang II,
      whereas mean arterial pressure (MAP) was significantly increased. Pulse pressure
      amplitude (PPA) was not affected by Ang II administration. There was a high
      degree of correlation between changes in RIs and the analogously calculated
      PPA/systolic blood pressure during Ang II infusion, which indicates that the
      changes in RI after Ang II administration can be attributed to changes in
      systemic haemodynamics. Calculation of total local ocular blood flow from fundus
      pulsation amplitudes and changes in flow pulsatility in the ophthalmic artery
      further argue against significant blood flow changes after Ang II administration.
      CONCLUSIONS: Interpretation of data from Doppler sonography and laser
      interferometry must be done very carefully when concomitant changes in systemic
      haemodynamics occur. RI cannot necessarily be taken as an index of distal
      vascular resistance in these cases and changes in MFV can be caused by changes in
      vessel diameter or in blood flow. Moreover, FPA cannot be taken as a measure of
      ocular blood flow if no additional data on flow pulsatility are available. The
      combination of our systemic and local haemodynamic data indicates that cerebral
      and ocular circulation are comparably insensitive to changes in local Ang II
      concentrations. Fundus pulsation and blood flow velocity measurements indicate
      that neither choroidal nor optic nerve head blood flow are significantly affected
      by administration of Ang II.

PMID- 9159567
TI  - Genetics and the therapy of cardiovascular disease.

PMID- 9159568
TI  - Why no mention of domestic violence articles on January cover?

PMID- 9159569
TI  - Authors misunderstood regarding position on instance-based models of diagnostic
      reasoning.

PMID- 9159570
TI  - An economist's view of the future financing of AHCs.

PMID- 9159571
TI  - Undergraduate education on HIV/AIDS.

PMID- 9159572
TI  - CBS program promotes strong interdisciplinary foundation.

PMID- 9159573
TI  - A promising process for creating an AHC-managed care organization alliance for
      research and care.

PMID- 9159574
TI  - Old management techniques should guide medicine's future.

PMID- 9159575
TI  - Managed care and medical education: hard cases and hard choices.
AB  - As managed care becomes more and more dominant in U.S. health care, it is coming
      into conflict with medical education. There are historical reasons for this:
      medical education traditionally excluded physicians who chose to work in health
      plans, and for profit managed care has tended to avoid subsidizing medical
      education. In order to improve the climate, three changes are necessary: medical
      education must understand the tense history of discord between the two;
      distinctions must be made between responsible and irresponsible managed care
      plans; and medical educators should not assume they own the moral high ground.
      Arrogance, a gross oversupply of physicians and especially specialists, scandals
      and fraud, an often callous attitude toward the poor, and other sins can be laid
      at medical education's door. The worse threat for both sides is that the public
      and payers could simply abandon both, leading to underfunding for health
      professions education, a society that does not trust its health care system, and
      the loss of superb teaching organizations. To prevent this, managed care and
      medical education should work together to solve several difficult problems: how
      to shrink the medical education infrastructure; how to report honestly the uses
      to which medical education funds are put; and how to identify and end
      irresponsible behavior on the part of health plans and medical education entities
      alike. If the two sides can exercise leadership in these areas, they will be able
      to protect and enhance the singular place of honor that medical education holds
      in this society.

PMID- 9159576
TI  - Managed care, ethics, and academic health centers: maximizing potential,
      minimizing drawbacks.
AB  - As academic health centers (AHCs) enter into various forms of managed care, they
      face a number of managed care's well-known ethical issues: utilization controls
      and loss of clinical autonomy; incentives and conflicts of interest; strained
      collegial relations; and questionable origin and validity of practice guidelines.
      Also, special issues arise regarding teaching relationships, faculty structure,
      and standards of care. Although the ethical hazards of current forms of managed
      care are quite pervasive and arise largely through short-sighted cost controls,
      emerging forms of integration and payer-level capitation permit considerably
      greater flexibility to provide care that is coherent, comprehensive, even
      creative. AHCs, as integrated multispecialty group practices, may be in a
      surprisingly good position to explore the best possibilities of global capitation
      while minimizing the ethical drawbacks of current forms of managed care.

PMID- 9159577
TI  - The need for comprehensive data on educational affiliations between academic
      health centers and managed care organizations.
AB  - Because of the emerging dominance of managed care, it is important to encourage
      the development of partnerships and affiliations between academic health centers
      (AHCs) and managed care organizations (MCOs) to train tomorrow's physicians to
      operate effectively in the new health care environment. But to what extent do
      such relationships exist now. In 1996, the authors sought to identify existing
      databases on the availability and extent of existing education partnerships and
      affiliations between AHCs and MCOs and the availability of such information to
      policymakers, the educational community, students, and residents. Despite a
      thorough search of the literature and interviews with representatives of
      education and practice organizations and with other experts in the medical
      education and managed care fields, the authors found no centralized or even
      partly centralized database on opportunities for training in managed care
      settings or on AHC-MCO partnerships. However, anecdotal evidence revealed eight
      such partnerships, each different from the others, that can serve as models for
      future partnerships; these are described. The authors speculate about why there
      are not more data describing AHC-MCO partnerships. They conclude by stating that
      the health care and health education industries have a variety of professional
      associations that could work together to assemble and make available such data to
      help build the educational and information infrastructure needed to train future
      physicians.

PMID- 9159578
TI  - The Tufts partnership for managed care education.
AB  - The authors describe the formation and the academic activities of the Tufts
      Managed Care Institute, a collaborative venture of Tufts University School of
      Medicine and Tufts Health Plan, an independent-practice-association (IPA)-model
      health maintenance organization (HMO). In 1994, the dean of the medical school
      and the CEO of the HMO recognized the need for collaboration to prepare students
      and practitioners for high-quality, cost-effective practice in a managed care
      environment. They established an advisory committee to oversee a six-month
      feasibility study to interview experts and opinion leaders and identify critical
      characteristics of the ideally prepared managed care practitioner. In 1995, with
      start-up funding from the HMO, the institute began its operations as a
      freestanding enterprise with board representation from the two sponsoring
      institutions. While many of the institute's programs have been developed for
      practicing physicians and other health care professionals, this article focuses
      on the academic activities. For medical students, the approach has been to blend
      managed care principles and practices into existing courses, problem-based
      learning cases, and clerkships, rather than creating separate managed care
      courses. For primary care residents, the institute has a grant to develop managed
      care curricula in conjunction with Tufts-affiliated residency training programs.
      Faculty development is accomplished through dedicated workshops and seminars, and
      through increased dialogue between traditional faculty and managed care
      professionals. In all of its programs and activities the institute has fostered
      greater contact and collaboration between colleagues from both sides of the
      health plan-academia "divide." Operationally, the institute structure, with
      dedicated full-time administrative staff, provides the singular focus necessary
      to establish managed care education as a top priority for the partnership. At the
      same time, sustaining this freestanding organization and infrastructure requires
      increased resources. Initial responses to the institute's programs and activities
      have been positive, both from the local Tufts community and from external
      parties. Yet the partnership must establish methods to evaluate the institute's
      long-term impact in its efforts to help practitioners succeed in a transforming
      landscape.

PMID- 9159579
TI  - Ideas for medical education.

PMID- 9159580
TI  - Ambulatory teaching "lite": less clinic time, more educationally fulfilling.
AB  - Typically, the primary instructional method for ambulatory care education is
      direct interaction between a preceptor and a learner during a patient encounter.
      This paper describes instructional strategies teachers and learners can use in
      ambulatory care training that can occur before or after scheduled clinic hours,
      thus providing instruction without disrupting a preceptor's busy clinic. First,
      they describe how preceptors and clerkship or residency-program directors can
      orient learners prior to their arrival at assigned sites, so that learners are
      better prepared to assume their patient-care responsibilities. Then they discuss
      strategies for making use of various types of conferences and independent
      learning activities to enhance learners' clinical experiences. Conferences and
      independent study projects that occur before clinic hours can help learners bring
      a higher level of thinking and clinical sophistication to their role in the
      ambulatory care site; conferences and independent study activities that occur
      after clinic hours give learners an opportunity to reinforce and expand on what
      they have learned during clinic. In this way, learners' educational experiences
      are enhanced, the best use is made of preceptors' time and expertise, and clinic
      efficiency is not disrupted.

PMID- 9159581
TI  - Why the university-based medical school should survive: a historical perspective.
AB  - Universities and medical education have been allied since the Middle Ages. In the
      United States, proprietary medical schools began to unite with universities at
      the turn of the century. At the end of the century, this traditional alliance is
      being questioned, even threatened, by marketplace demands, and medical schools
      and their universities continue to deal with internal struggles regarding
      teaching and research goals, and funding. In this paper, the author defines and
      discusses the origins of university-medical school tensions, provides a brief
      review of the history of university-based medical education in the United States,
      and describes some of the advantages and disadvantages of the alliance. Finally,
      he makes a case for why medical education must continue to be grounded in
      universities.

PMID- 9159582
TI  - Pew catalyzes education partnerships with managed care organizations.

PMID- 9159583
TI  - The Federal Demonstration Partnership, phase III: a cooperative venture between
      federal agencies and participating institutions.

PMID- 9159584
TI  - A longitudinal study of substance use and abuse in a single class of medical
      students.
AB  - PURPOSE: A longitudinal study to ascertain the attitudes toward, and habits of,
      substance use among a single class of medical students. METHOD: A single class
      from a northeastern medical school was surveyed in both its first year (February
      1991, 176 students) and its third year (May 1993, 170 students). The students
      were asked to report how frequently during the prior year they had used drugs or
      alcohol, and whether their use of each substance had increased, decreased, or
      remained the same since entering medical school; to identify any family members
      with histories of alcohol or drug problems; and to report any incidence during
      the prior year of ten behaviors associated with substance dependence. The
      students were also asked to indicate their agreement or disagreement with 11
      attitudinal statements. Additional attitudinal items asked the students to
      identify three major deterrents to the abuse of drugs and alcohol, and what they
      had done if they had become aware of a classmate with a drug or alcohol problem.
      Chi-square analysis and two-tailed t-tests were used to compare data from the two
      surveys. RESULTS: The response rates in the first and second surveys were 96.9%
      and 81.8%, respectively. Use of licit and illicit substances was comparable to
      that of chronological peers and prior national studies of medical trainees. Most
      of the students admitted to using alcohol at least once in the prior year (91.8%
      and 95%, respectively). In both years marijuana was the illicit drug used most
      often. Although there was a slight increase over time in the use of
      benzodiazepines (2.4% to 5.8%) and a decrease in the use of marijuana (29.4% to
      21.7%), these changes were not significant. Few of the students in their third
      year reported using any substance other than alcohol more than once a month. In
      general, a greater percentage of the students reported a decrease rather than an
      increase in the use of a substance since entering medical school; the primary
      exception was for wine. As they progressed in their training, the students became
      less concerned about the effect of substance use on their performance and more
      likely to be embarrassed about admitting to an addiction. Although in each year a
      few of the students appeared to be at risk for substance dependence (8.9% and
      3.5%, respectively), no student came to the attention of the administration
      because of problems related to substance use. While most of the students were
      unaware of any classmate who had a problem, half of those who were aware had done
      nothing, and the balance had rarely sought assistance from the faculty or
      administration. CONCLUSION: Although there was no evidence that substance use was
      a major problem, a few of the students appeared to be at risk for drug or alcohol
      dependence. Appropriate intervention, support, and referral systems should be
      identified for the few who may be at risk, and increased educational efforts are
      needed to help all students address this issue with their peers and, ultimately,
      with their patients.

PMID- 9159585
TI  - The effects of precepting on and the support desired by community-based
      preceptors in Iowa.
AB  - PURPOSE: To survey community-based family physician-preceptors about teaching
      costs, issues, and support desired. METHOD: In late 1994 a questionnaire was
      mailed to all 139 community family physicians who served as preceptors for the
      University of Iowa College of Medicine's third-year family practice
      preceptorship. The questionnaire contained items regarding teaching costs and the
      kinds of assistance desired from the university, the difficult and enjoyable
      aspects of precepting, and demographic data. Analyses were done to explore the
      associations between the preceptors' demographic variables and the effects of
      precepting on number of patients seen, practice income, and time spent at work.
      Also tested were the associations between the demographic variables and the kinds
      of support desired. RESULTS: In all, 130 surveys were returned, for a response
      rate of 94%. Nearly all of the respondents were Caucasian, male, and residency
      trained; 61% were in group practices. While precepting, 87% spent more time at
      work, 31% saw fewer patients, and 25% lost practice income; mean daily cost
      estimates of precepting were 51 more minutes at work, 1.4 fewer patients seen,
      and $34 in lost income. The support the preceptors were most interested in
      receiving was training in and access to computer-based information. Financial
      compensation was desired more often by the physicians whose first year of
      practice was after 1977 (p = .009). Motivations for precepting included positive
      interactions with students and enjoyment of teaching. Time concerns were
      overwhelmingly the most difficult aspect of precepting. CONCLUSION: The
      physicians-many of whom noted their enjoyment of teaching for its intrinsic
      rewards-spent a significant amount of extra time teaching while precepting, and
      thus both lost income and saw fewer patients. Medical schools need to recognize
      the valuable contributions of preceptors and find ways to support them.

PMID- 9159586
TI  - Assessing residents' readiness for working in a managed care environment.
AB  - PURPOSE: A the pilot study to assess the state of residents' training for
      practice in a managed care environment. METHOD: In May and June 1996, all 178
      residents at the University of Kentucky College of Medicine in six programs were
      approached to participate in the study. An instrument was created to assess the
      residents' knowledge of, attitudes toward, and exposure to managed care, as well
      as their perceptions of their residency experience. Attitudinal items were
      measured using a five-point Likert scale (1 = strongly agree, 5 = strongly
      disagree), as were the assessments of experience (1 = excellent, 5 = poor).
      Bivariate statistics were computed between the number of correct responses to the
      knowledge questions and both the year of training and reported exposure to
      managed care. The relationship between exposure and knowledge was analyzed using
      a two-tailed t-test. A Pearson product-moment correlation was computed between
      residents' knowledge and year of training. RESULTS: In all, 140 (79%) residents
      participated, 76% of whom were men. Seventy-three percent of the residents rated
      their experiences as fair or poor; the mean rating across all the residents was
      3.8 (SD, 0.8). Among those reporting some exposure, attitudes toward the
      effectiveness of their exposure generally ranged from neutral to negative. Across
      all the residents, the mean number of correct responses to the five knowledge
      questions was 3.2 (SD, 1.1). No statistically significant relationship was found
      between year of training and the number of correct responses. The residents who
      reported some exposure to managed care had a significantly higher mean number of
      correct responses than did those with no reported exposure (3.4, SD, 1.1, vs 2.8,
      SD, 1.3, p = .04). CONCLUSION: The residents reported limited exposure to managed
      care and that their training experience did not prepare them for working in
      managed care; this was confirmed (in a limited way) by the responses to the
      knowledge questions. As managed care expands in the United States, the systematic
      incorporation of managed care instruction into training is necessary to
      appropriately prepare residents for future practice.

PMID- 9159587
TI  - Factors associated with family physicians' involvement in research in Israel.
AB  - OBJECTIVES: To identify the factors that encourage or deter family medicine
      physicians and residents in Israel from participating in research. METHOD: In
      October 1995, a questionnaire containing items on demographic variables, research
      attitudes, and academic and research activities in primary care settings was
      mailed to a random sample of 200 family medicine physicians and residents (out of
      approximately 600) employed by the General Sick Fund, the largest health
      maintenance organization in Israel. The questionnaire also contained items
      regarding difficulties in participating in research and asked for opinions about
      several general statements about research in family practice. RESULTS: In all,
      190 physicians responded, for a response rate of 95%. Based on their responses,
      the respondents were divided into four groups by amount of research involvement.
      Univariate analysis using the chi-square test was used for the comparison of
      variables among the four groups. The respondents reporting greater knowledge of
      and involvement in research were, by and large, men (p = .01) who were qualified
      specialists with academic status (p < .00001). They also taught students (p =
      .0005) and residents (p < .0005), participated in more conferences (p < .0005),
      and while in residency training had had a mentor who encouraged involvement in
      research (p = .0001). CONCLUSION: Research is essential to family medicine with
      regard to both primary care practice and academic activities, its development,
      however, has been inhibited. Given the results of this preliminary study, family
      medicine residency programs would be well advised to assign a research mentor to
      every resident; also, time and resources should be devoted to research in
      postgraduate training programs. Perhaps more important, women physicians in
      Israel should be encouraged to participate more actively in research, and support
      for them in their special needs should be made available.

PMID- 9159589
TI  - Evaluating GPAs and MCAT scores as predictors of NBME I and clerkship
      performances based on students' data from one undergraduate institution.
AB  - PURPOSE: To examine the relationships among undergraduate student
      characteristics, standardized indicators of medical school academic performance,
      and clinical performances in an institution where the undergraduate grading
      system was not a confounding factor. METHOD: In 1993 data were collected
      retrospectively for the classes of 1990-1993 in the University of California,
      Riverside (UCR)/University of California, Los Angeles, Biomedical Sciences
      Program, in which all the students completed their undergraduate studies at UCR.
      Data were collected on the students' demographic characteristics, undergraduate
      grade-point averages (UGPAs), Medical College Admission Test (MCAT) scores,
      National Board of Medical Examiners Part I (NBME I) scores, and clinical
      performances as measured by core clerkship grades. Regression analyses were used
      to evaluate (1) the relationship between clinical performances and data available
      at admission and (2) the relationship between NBME I scores and the same
      variables. The top and bottom 25% of each class were identified by UGPAs and
      compared by their NBME I scores and clinical performances to determine whether
      differences noted at admission continued to separate the students. Differences
      were tested using independent two-tailed t-tests. RESULTS: Of the 92 students,
      data were available for 88 (96%); 39% were female and 38% were foreign-born. The
      sample was fairly heterogeneous in terms of UGPAs, MCAT scores, clinical
      performance grades, and NBME I scores. Results of the first regression analysis
      indicated that mean clinical performance was not related to any of the
      undergraduate predictors of performance or to the students' demographics. The
      second regression analysis indicated that MCAT scores and cumulative science
      UGPAs were related to performance on the NBME I, as were country of origin and
      sex. The students in the top and bottom 25% differed significantly in their
      scores on the NBME I, but not in their clinical performances. CONCLUSION:
      Although UGPAs and MCAT scores are good indicators of NBME I performance, they
      are still not useful in predicting clinical performance, even when the students'
      data are taken from the same undergraduate institution.

PMID- 9159588
TI  - Using follow-up support with grand rounds CME in community hospitals.
AB  - PURPOSE: To determine the proportion of regional primary care physicians who
      would attend grand rounds on preventive services and their interest in and use of
      free follow-up enabling and reinforcing assistance to implement changes in their
      practice routines. METHOD: From January to July 1992 grand rounds on early
      detection of cancer were offered by Dartmouth Medical School at 38 acute care
      community hospitals in New Hampshire and Vermont. The target audience of 679
      family physicians and general internists was identified through state medical
      society and hospital attending lists. The hour-long grand rounds program
      described preventive service guidelines and an office system that promoted their
      implementation. Follow-up practice support with planning, office staff training,
      and materials were offered to augment the effects of the grand rounds. Attendance
      was determined by sign-in documents. In addition, all attendees were asked to
      complete a survey regarding practice and personal characteristics and interest in
      follow-up assistance. Statistical comparisons were made using chi square and
      Fisher's exact tests. RESULTS: In all, 261 family medicine physicians and general
      internists (38.4%) attended. Certain categories of physicians were more likely to
      have attended: internists, those younger than 55 years, and physicians on the
      staffs of hospitals located in small towns. Assistance was requested by 70.1% of
      the attendees; many requested more than one type of assistance. Physicians from
      hospitals in smaller towns were more likely to show interest in follow-up
      assistance and use it when offered. CONCLUSION: Many of the grand rounds
      attendees were receptive to follow-up assistance that could improve the
      preventive services they provided. Most hospitals offer grand rounds, and many
      organizations have interest in and resources for helping physicians provide high
      quality care. Future research should establish the best linkage to the actual
      care provided in practices and explore the relevance of similar approaches to
      clinical areas beyond prevention.

PMID- 9159590
TI  - An assessment of residents' competence in the delivery of bad news to patients.
AB  - PURPOSE: To assess the level of residents' competence in delivering bad news to
      patients. METHOD: In June 1995, 25 residents (of 116) in the Wayne State
      University general internal medicine residency program volunteered to participate
      in the study, which consisted of videotaped interviews of a simulated patient
      whose profile had been developed to highlight the delivery of a diagnosis of lung
      cancer. The residents were evaluated using an instrument based on a review of the
      current literature regarding the skills considered necessary for giving bad news
      in a caring and informative manner. The instrument contained 16 items, seven in
      the informative category and nine in the affective category. Each item was rated
      on a five-point Likert scale (from 1 = "doesn't do this" to 5 = "does this very
      well"). A rating of > or = 4 on any item indicated competence in the skill area
      measured by that item. All interviews included in the study were rated by all six
      of the authors. Interrater reliability was calculated to be .91. RESULTS: In all,
      22 interviews (three by women, 19 by men) were included in the study. The
      residents' ages ranged from 26 to 35 years; the numbers of years since graduation
      from medical school ranged from two to six. Twenty were third- or fourth-year
      residents ready to graduate; the other two were completing their first year. Mean
      ratings in the informative category ranged from 1.51 to 4.51; for three items,
      mean ratings were > or = 4. The total mean rating for all the items in this
      category was 3.42. Mean ratings in the affective category ranged from 1.15 to
      4.75; for three items, mean ratings were > or = 4. The total mean rating for all
      the items in this category was 3.45. CONCLUSION: The residents showed a general
      lack of competence in delivering bad news. The skill items with the lowest
      ratings were primarily related to eliciting the patient's perspective, which may
      represent a weakness on the part of the residency program in teaching the
      residents to use a "patient-centered" interviewing style. The results of this
      study will form the basis of a curriculum to improve residents' comfort with and
      skills for delivering bad news to patients.

PMID- 9159591
TI  - A pilot study of the use of the analytic hierarchy process for the selection of
      surgery residents.
AB  - PURPOSE: To compare a specific decision-making process-the analytic hierarchy
      process (AHP)-with the traditional informal selection process in the selection of
      general surgery residents. METHOD: The study focused on 1994 and 1995 applicants
      for the four positions in the five-year general surgery residency program at the
      Graduate Hospital in Philadelphia. Three criteria were used: academic
      performance, personal fit, and surgical appropriateness. The relative importance
      of each was determined by pairwise comparison. For each hierarchy level, these
      comparisons were combined into a pairwise comparison matrix, and weights were
      determined for each criterion and rating category. The rating-category weights
      for each criterion were scaled so that outstanding received the full criterion
      weight. Each applicant was interviewed by three committee members and rated with
      both the AHP system and the traditional 0-10 scoring system. In both cases the
      rating scores were averaged to create a single score for each applicant. The
      final ranking list (advocacy ranking) was compiled at a meeting of the entire
      selection committee, during which each member spoke on behalf of the candidates
      he or she had interviewed. RESULTS: Significant Spearman correlations were found
      between the AHP ranking and the traditional ranking in both years (1994: n = 26,
      r = .63, p = .0005; 1995: n = 25, r = .061, p = .0012). The AHP ranking was also
      significantly correlated with the advocacy ranking in 1994 (n = 26, r = .43, p =
      .0273); however, there was no significant correlation found in 1995. In 1994 the
      traditional ranking significantly correlated with the advocacy ranking (n = 26, r
      = .40, p = .0423). This was not the case in 1995, suggesting that the results of
      the interviewing process had minimal influence on the outcome of the selection
      process that year. CONCLUSION: The findings from this pilot study support the use
      of the AHP as a viable alternative for the selection of surgical residents.
      Although the small sample size limits the generalizability of the results, the
      AHP is a quantitative alternative to the traditional, unwieldy, and subjective
      selection process. Quantitative assessment and ranking of all aspects of a
      candidate's attributes and performance allow a program to more closely match a
      candidate to that particular institution.

PMID- 9159592
TI  - Student feedback comments on examination questions foster fairness, item
      validity, and learning.

PMID- 9159593
TI  - Restrictive covenants in internal medicine training program contracts.

PMID- 9159594
TI  - Changes in academic emergency departments in response to market-driven health
      care reform.

PMID- 9159595
TI  - Residents' perceptions of inpatient and outpatient rotation characteristics.

PMID- 9159596
TI  - Cardiac natriuretic peptides as predictors of mortality.

PMID- 9159597
TI  - Associations between atrial natriuretic peptides, echocardiographic findings and
      mortality in an elderly population sample.
AB  - OBJECTIVES: To examine associations of N-terminal and C-terminal components of
      the proatrial natriuretic peptide [ANP (1-98) and ANP (99-126), respectively],
      with echocardiographic measurements of left ventricular structure and performance
      and with the function of the aortic and mitral valves in old age. To compare the
      predictive value of the atrial peptides and echocardiographic data for short-term
      mortality. DESIGN: A population based survey with 1.5-year mortality follow-up.
      SETTING: University hospital. SUBJECTS: Three-hundred and thirty-three people
      aged 78-88 years. MAIN OUTCOME MEASURES: (i) Plasma ANP (1-98) and ANP (99-126);
      (ii) M-mode and Doppler echocardiographic measurements of left atrial diameter;
      left ventricular diameters, mass and fractional shortening; peak transmitral
      velocities; aortic valve area, aortic regurgitation jet length and mitral
      regurgitant jet area; (iii) total and cardiovascular 1.5-year mortality. RESULTS:
      ANP (1-98) correlated with left atrial diameter (r = 0.33; P < 0.001), left
      ventricular mass (r = 0.19; P < 0.001), fractional shortening (r = -0.16; P <
      0.01) and the early-to-atrial peak transmitral velocity ratio (r = 0.23; P <
      0.001). Also, ANP (1-98) predicted the degree of aortic valve obstruction and the
      severity of aortic and mitral regurgitation. Associations of ANP (99-126) with
      echocardiographic data were much weaker. Aortic valve stenosis and ANP (1-98)
      were independent predictors of age- and sex-adjusted total and cardiovascular
      mortality at 1.5 years of entry. CONCLUSIONS: Circulating ANP (1-98) correlates
      with left atrial size, with left ventricular mass and performance and with the
      severity of aortic and mitral valve dysfunction in persons representing the
      general elderly population. ANP (1-98) also predicts both total and
      cardiovascular mortality.

PMID- 9159598
TI  - Atrial natriuretic peptides predict mortality in the elderly.
AB  - OBJECTIVES: To ascertain whether atrial natriuretic peptides could be used as
      prospective and independent predictors of total mortality in an elderly
      population. DESIGN: Atrial natriuretic peptides, ANP(1-98) and ANP(99-126), were
      measured in 541 subjects from the 85-year-old population of Gothenburg, Sweden.
      Before the study cardiovascular disorders such as congestive heart failure,
      ischaemic heart disease, hypertension and atrial fibrillation were defined. Total
      mortality was recorded during the prospective 60-month follow-up period. SETTING:
      Individuals aged 85 years from the population of Gothenburg, Sweden, were visited
      once at home and made one visit to Vasa Hospital. MAIN OUTCOME MEASURES: Sixty
      month mortality in relation to circulating concentrations of atrial natriuretic
      peptides. RESULTS: Circulating concentrations of ANP(1-98) and ANP(99-126) were
      significantly correlated with 60-month mortality in the total study population
      (ANP(1-98), P < 0.001: ANP(99-126), P < 0.01). In subjects with cardiovascular
      disorders, 60-month mortality was significantly correlated with increased
      concentrations of ANP(1-98) (P < 0.01) and ANP(99-126) (P < 0.05). In subjects
      with no defined cardiovascular disorder, 60-month mortality was significantly
      correlated with increased ANP(1-98) concentrations (P < 0.01). CONCLUSIONS: In
      the elderly population, atrial peptides predict mortality in subjects with
      defined cardiovascular disorders as well as in the total population and may
      predict future cardiovascular disorder.

PMID- 9159599
TI  - Cholesterol issues as viewed from the United States.

PMID- 9159600
TI  - Secondary prevention of heart disease amongst patients with lipid abnormalities:
      practice and trends in the United States.
AB  - Patients with established coronary disease and abnormalities of lipid metabolism
      represent a particularly important subgroup, since their mortality risk is
      typically 10 times greater than that amongst-subjects with comparable risk
      factors but no clinical history. Such patients are commonly treated initially
      with anti-anginal therapy; if ischaemic symptoms persist they often undergo
      revascularization (bypass or angioplasty). While invasive procedures restore
      blood flow and relieve ischemia, they do not, in most cases, reduce risk of
      subsequent MI or death, or alter the underlying atherogenic process(es). Despite
      this, there has been a progressive 54% decline in age-adjusted cardiac mortality
      over the period 1960-1995, which appears best attributable to US lifestyle
      changes. In particular, the past decade has provided compelling evidence for the
      merits of a fourth approach: comprehensive risk factor management. Clinical
      outcome studies have confirmed the substantial merit of aspirin prophyllaxis and
      of intensive lipid-lowering therapy in secondary prevention. Prospective
      angiographic trials and evidence from studies of vascular biology have provided
      insight into mechanisms of benefit. As a consequence, lipid therapy and aspirin
      use have increased greatly among middle aged and older US citizens, especially
      those with CAD. The growth of comprehensive medical management now rivals that of
      invasive revascularization in secondary prevention.

PMID- 9159601
TI  - Primary prevention of coronary heart disease: role of cholesterol control in the
      United States.
AB  - The benefit of cholesterol-lowering drug therapy in patients with existing
      coronary heart disease (CHD) is well established through clinical trials.
      Prevention of recurrent coronary morbidity and mortality in CHD patients is
      called secondary prevention. In contrast, primary prevention is delaying or
      preventing altogether new-onset-CHD. There are three categories of primary
      prevention: high-risk, moderate-risk, and long-term (life-time). A recent
      clinical trial has documented benefit of cholesterol-lowering drugs for
      prevention of coronary morbidity and mortality and total mortality in hyper
      cholesterolemic, middle-aged men. This trial lends support for including
      aggressive cholesterol reduction in high-risk primary prevention. However, for
      such therapy to be cost effective at present-day prices of cholesterol-lowering
      drugs, only those patients in the higher ranges of risk can be selected for
      treatment. This leaves a large number of people at moderately high risk for
      premature CHD because of high cholesterol levels. These persons deserve increased
      professional attention to risk reduction. In general the nondrug approach is
      indicated. The latter approach includes eliminating other risk factors, e.g.
      cigarette smoking and hypertension, and reducing serum cholesterol levels by
      decreased intakes of saturated fatty acids, cholesterol, and excess total
      calories. Some moderate-risk patients may require low doses of cholesterol
      lowering drugs to achieve the goals for cholesterol reduction. Finally, public
      health strategies need to be developed for applying the same nondrug approach for
      the general population for reducing the overall incidence of CHD.

PMID- 9159602
TI  - Cholesterol management in women and the elderly.
AB  - Women, like men, die mostly of coronary atherosclerosis, although atherosclerotic
      death in women occurs 5-10 years later than in men. Major risk factors predict
      coronary risk in women and men. What evidence is available suggests that women,
      similar to men, benefit from cholesterol lowering. Older individuals with
      symptomatic coronary disease but a relatively good prognosis should be offered
      the same benefits from secondary prevention as younger individuals.

PMID- 9159603
TI  - The problem of compliance to cholesterol altering therapy.
AB  - This review's purpose is to describe for the practicing clinician the current
      knowledge about patient compliance to cholesterol-altering drugs and about
      procedures for compliance management applicable to clinical practice in the
      United States. Compliance is defined for four commonly measured major steps and,
      based on recent electronic monitoring data, for three quantitative categories of
      active medication-taking. The concepts and definition of compliance are
      undergoing evolutionary changes due to the measurement and availability of new
      dimensions through electronic monitoring of patient compliance. Substantial non
      compliance to cholesterol-altering drugs has been reported in nine large clinical
      trials for primary and secondary prevention of coronary heart disease, in two
      HMOs, and, using electronic monitoring of compliance, in one clinical trial and a
      selected practice. The risks of treatment discontinuation increased continuously
      during treatment and totaled from 6 to 30% after 5 years. Patterns of day-to-day
      partial compliance are emerging. Procedures and knowledge for clinical management
      of compliance are described including methods of measuring compliance, risk
      factors for non-compliance, standards for compliance performance, epidemiology of
      compliance, procedures for managing compliance at the start of therapy and for
      addressing compliance problems during established treatment, simple office
      assessment of compliance by brief interview questions, compliance aids,
      prediction of compliance, and education and training of medical-care personnel in
      compliance management.

PMID- 9159604
TI  - Familial amyloidosis in one Chinese family: clinical, immunological, and
      molecular genetic analysis.
AB  - Three members of a Taiwanese kindred developed severe, systemic, early onset (<
      age 25 years), biopsy-proven amyloidosis. Clinical features included upper and
      lower extremity sensorimotor neuropathy, abdominal pain, vomiting, corneal
      ulcerations, cardiomyopathy, and syncope. Immunohistochemical analysis indicated
      that the deposits consisted of transthyretin. Molecular genetic studies revealed
      a heterozygous codon 55 point mutation, resulting in a proline for leucine
      substitution, a mutation previously associated with aggressive familial
      amyloidosis in a US kindred of Dutch and German descent. The clinical courses and
      echocardiographic findings are typical for many types of amyloidosis; the
      pathologic data and genetic studies were necessary to establish a precise
      diagnosis.

PMID- 9159605
TI  - Internal jugular vein thrombosis after cervical traction.
AB  - A clinically and roentgenographically typical case of internal jugular vein
      thrombosis is presented in a patient having undergone repeated sessions of
      Glisson traction for neck and backache. In this mode of therapy, axial traction
      is applied to the neck by attaching a weight, via a pulley, to a construction of
      straps encompassing the head. This particular trauma to the neck has not
      previously been described to be associated with spontaneous internal jugular vein
      thrombosis.

PMID- 9159606
TI  - Chinese herbs and warfarin potentiation by 'danshen'.
AB  - Drug interactions with warfarin can be dangerous and although common drug
      interactions are now well recognized those with Chinese herbs are not widely
      appreciated. 'Danshen' is a herbal medicine often used for various complaints,
      particularly cardiovascular, in the Chinese community. We report a case of
      danshen-induced overcoagulation with severe and dangerous abnormalities of
      clotting in a patient with rheumatic heart disease.

PMID- 9159607
TI  - Implementation of a new patient care role: concept to reality.

PMID- 9159608
TI  - Quality nursing care: leadership makes the difference.

PMID- 9159609
TI  - Focus groups: their use in administrative research.

PMID- 9159610
TI  - Job strain among registered nurses and other hospital workers.
AB  - OBJECTIVE: The authors describe factors associated with job strain for various
      job titles in the acute care hospital using the Karasek Job Strain Model, discuss
      the reliability and validity of the Job Content Questionnaire, and discuss use of
      the model to enhance the work environment. BACKGROUND: The Karasek Job Strain
      Model has been used to describe many occupations in the United States and other
      countries. Some research indicates that occupations that arouse stress hormones
      are those in which employees have little job control or must complete
      psychologically demanding tasks, such as those under time pressure, and these
      positions can be describe as high-strain jobs. METHOD: This descriptive
      correlational study was conducted at five tertiary care hospitals on the West
      Coast. A purposive volunteer sample of staff members working at least 20 hours
      per week in the adult medical-surgical and specialty nursing units was recruited.
      RESULTS: Mean scores for each of the nursing units and the overall mean scores
      for the staff in the initial analysis fell into the Active Work quadrant of the
      Karasek Job Strain Model. When nursing job titles were analyzed, registered
      nurses had significantly higher Decision Latitude scores than did nurse
      assistants (P < 0.001) and clerical staff (P < 0.001), but there were no
      significant differences for Psychological Demands. CONCLUSIONS: Working with
      nurse assistants to appropriately increase decision latitude related to their
      work has the potential to enhance the work environment by reducing job strain and
      improving staff health and morale.

PMID- 9159611
TI  - The relation between leadership style and empowerment on job satisfaction of
      nurses.
AB  - OBJECTIVE: The authors explore the relation between leadership style and
      empowerment and its effect on job satisfaction among the nursing staff of a
      regional medical center. BACKGROUND: Several empirical studies on
      transformational leadership-found that transformational leadership behaviors were
      positively related to work team success and leadership effectiveness.
      Transformational leadership processes have also been suggested to enhance
      followers' work-oriented values and shape the self-efficacies of followers.
      Employee empowerment may be influenced by the perception that the organization
      cares about its employees' well-being and that their work is valued. Empowering
      nurses may increase job satisfaction and improve patient care. Leadership style
      and empowerment influence job satisfaction among workers. METHODS: All nursing
      department staff were invited to complete a self-report questionnaire with no
      identifying information. Leadership style was measured using Bass's Multifactor
      Leadership Questionnaire, empowerment was measured with items from Spreitzer's
      Psychological Empowerment instrument, and job satisfaction was measured by Warr,
      Cook, and Wall's job satisfaction questionnaire. RESULTS: Both transformational
      and transactional leadership were positively related to job satisfaction, as was
      empowerment. Differences in the contributions of empowerment and leadership style
      in predicting job satisfaction for licensed and unlicensed workers was evident.
      CONCLUSION: Designing interventions that allow for the relative influence of
      leadership style as well as empowerment on varying classifications of nursing
      personnel may be a more effective strategy and have a greater effect on staff
      attitudes and behaviors.

PMID- 9159612
TI  - Preparing to change from acute to community-based care. Learning needs of
      hospital-based nurses.
AB  - OBJECTIVE: Increasingly, professional nurses will be required to function in
      practice settings other than acute care, yet little is known about how nurses
      perceive the skill sets required to practice in these nonacute care settings.
      This study explores nurses' perceptions and needs concerning the transition from
      acute to home care and community-based healthcare facilities. BACKGROUND: Because
      the healthcare reform environment of the 1990s mandates changes in the ways
      hospitals and hospital nurses care for patients, many nurses in acute care
      settings anticipate that their roles will include or perhaps shift completely to
      practice in the home and other community-based settings. How professional nurses
      perceive the skills required to practice in these nonacute care settings may well
      influence their willingness to accept work redesign initiatives and voluntary
      employment transitions that involve working outside the hospital setting.
      METHODS: Based on focus groups and the literature a three-part 56-item
      questionnaire was developed as the study instrument to assess skill needs and
      concerns related to functioning in the acute, home, and community-based setting.
      A total of 879 nurses representing various specialties in healthcare institutions
      in the Philadelphia and five-county surrounding areas participated. RESULTS: Test
      retest for the study instrument was 0.87 for a 2-week period, and alpha
      coefficients ranged from 0.90 to 0.94. Multivariate analyses revealed that
      proficiency on certain skill items in the acute care setting predicted feelings
      of proficiency in home and community-based settings. Based on regression and
      discriminant function analyses, top predictors and differentiators of proficiency
      in the nonacute care settings were wound care and dressing, knowledge of
      community resources, diabetic education, patient and family advocacy,
      communication with third-party payers, and neonatal care. CONCLUSIONS: Some
      nurses, such as those working in critical care, perceive themselves as being able
      to function proficiently in a wide variety of care settings-acute home, and
      community based. Furthermore, certain acute care skills were identified as top
      differentiators of proficiency in nonhospital settings, thus providing direction
      for nursing administrators and academic institutions. In addition, the tool
      developed for the study can serve as a self-assessment for individual nurses.

PMID- 9159613
TI  - Development of a scientifically valid coordinated care path.
AB  - OBJECTIVE: The goal of this study was to develop a method to scientifically
      create and validate a coordinated care path for use within any hospital setting.
      BACKGROUND: In an attempt to reduce the costs associated with high-volume and
      high-risk diagnosis, attention was focused on reducing patients' length of stay
      in the hospital. A method to reduce length of stay uses a coordinated care path.
      A path is a guideline used to manage the clinical care of selected patients. The
      literature is relatively silent regarding studies that have scientifically
      validated the use of these paths. METHODS: This project used a content validity
      method to validate the care path. Using current research findings, best practice
      standards both locally and nationally, a transdisciplinary team developed
      practice guidelines that included sequencing, timing of interventions, and
      expected patient outcomes. The path was rated by local and national experts using
      a four-point rating scale. Using Lynn's proportion of experts table computations,
      the validity of the path and each of its components was determined. RESULTS: Of
      161 items on the care path, 10 were not validated. The experts validated the
      instrument as a whole. Of the 161 items, 151 were validated. This is an
      instrument validation rate of 0.94. No additional changes or modifications to the
      path were suggested by the experts. The transdisciplinary team addressed the
      nonvalidated items. This method can be used to develop other coordinated paths
      for other diagnostic groups.

PMID- 9159614
TI  - Research-based planning for change: assessing nurses' attitudes toward governance
      and professional practice autonomy after hospital acquisition.
AB  - OBJECTIVE: This article describes one medical center's experience in using
      research to plan for nursing staff integration after hospital acquisition.
      BACKGROUND: Resistance to new policies, procedures, and standards; passive
      acceptance of new leadership; limited support for management plans; and failure
      to integrate with new nursing units are common staff reactions after
      acquisitions. Little has been written regarding which key staff variables to
      assess after acquisitions and how to use this data to plan for change. Structural
      contingency and attribution theory were used to guide leadership staff's
      assessment of acquired staff attributes to determine their congruence with
      concepts valued by the acquiring organization. METHODS: Qualitative and
      quantitative data were collected using a survey method. All 141 registered nurses
      and licensed practical nurses of the acquired medical center received a mailed
      survey. Sixty-six completed surveys were returned through the U.S. mail. No
      identifying information was placed on the survey to assure anonymity. RESULTS:
      The survey results described nurses perceptions of the advantages, concerns, and
      suggestions for a smooth transition after acquisition. In addition, the results
      clarified that nurses in the newly acquired hospital preferred a shared
      governance structure (congruent with the acquiring medical center's values) and
      the nurses perceived professional nursing autonomy was similar to that of nurses
      who worked at the acquiring medical center. CONCLUSIONS: By sharing the findings,
      both staffs were sensitized to the similarities among the staff as well as to
      their differences. Transition strategies were planned to capitalize on this
      knowledge. This process may be useful for other nurse executives to replicate as
      they guide their organizations through similar transitions.

PMID- 9159615
TI  - Inhaled nitric oxide and pentoxifylline in rat lung transplantation from non
      heart-beating donors. The Paris-Sud University Lung Transplantation Group.
AB  - BACKGROUND: In non-heart-beating donor lung transplantation, postmortem warm
      ischemia poses a special challenge. Inhaled nitric oxide and pentoxifylline have
      been shown to attenuate ischemia-reperfusion injury after lung transplantation.
      We hypothesized that concomitant administration of inhaled nitric oxide and
      pentoxifylline would result in a synergistic effect on ischemia-reperfusion lung
      injury. METHODS: Lungs were harvested from non-heart-beating donors after 30
      minutes of in situ warm ischemia, flushed, and stored for 2 hours at 4 degrees C
      before left lung transplantation in rats. Inhaled nitric oxide (30 ppm) was added
      during cadaver ventilation and reperfusion; pentoxifylline was given
      intravenously throughout reperfusion. The following groups were studied (n = 8
      each): control, pentoxifylline, nitric oxide, and nitric oxide+pentoxifylline.
      Hemodynamic indices and arterial blood gases were obtained after ligation of the
      right pulmonary artery. Lung myeloperoxidase and wet/dry ratio were measured
      after death. RESULTS: All rats that did not receive nitric oxide died within 10
      minutes after ligation. Inhaled nitric oxide significantly decreased pulmonary
      vascular resistance and improved recipient survival. Nitric oxide +
      pentoxifylline improved pulmonary vascular resistance, arterial oxygen tension,
      and survival even further and reduced lung myeloperoxidase as compared with the
      group that received nitric oxide only. Preservation solution flush time was
      significantly decreased in both groups receiving nitric oxide, suggesting that
      inhaled nitric oxide used during cadaver ventilation allows for a more even
      distribution of the preservation solution. CONCLUSIONS: We conclude that
      treatment with inhaled nitric oxide + pentoxifylline results in a synergistic
      protection from ischemia-reperfusion injury after non-heart-beating donor lung
      transplantation. This is likely the result of a dual action on the graft
      vasculature and neutrophil sequestration.

PMID- 9159616
TI  - Increased nitric oxide levels in exhaled air of rat lung allografts.
AB  - In organ transplantation nitric oxide has been reported to be involved in
      allograft rejection. We examined in a rat lung transplantation model whether
      nitric oxide is overproduced in acute rejection and can be detected in exhaled
      air. Thirteen rat right lung transplants were separated into three groups: group
      1 (n = 5), untreated allografts (Brown-Norway [RT1n] to Lewis [RT1l]); group 2 (n
      = 4), cyclosporine-treated allografts; and group 3 (n = 4), isografts (Lewis to
      Lewis). We examined exhaled nitric oxide levels with a chemiluminescence analyzer
      and chest roentgenograms on days 2 through 5. Histologic samples were obtained on
      days 3 and 5. On day 5, the recipients were killed and we measured exhaled nitric
      oxide from the right and left lungs separately. Blood samples were also obtained
      for measurement of serum nitrite/nitrate. The exhaled nitric oxide level in
      untreated allografts increased significantly from day 5 (63.9 +/- 39.2 ppb, p =
      0.0095) and was significantly higher than that in treated allografts (9.1 +/- 1.6
      ppb) (p = 0.0085) and isografts (6.9 +/- 0.5 ppb) (p = 0.0068). The nitric oxide
      level in untreated allografts (826.5 +/- 416.1 ppb) was 75 times as high as that
      from the contralateral normal left lungs (11.2 +/- 2.6 ppb) (p = 0.0118). The
      level of exhaled nitric oxide correlated significantly with the histologic
      rejection grade (p = 0.0001). There was no significant difference in the serum
      nitrite/nitrate levels between allografts and isografts. These data suggest that
      increased exhaled nitric oxide levels might reflect acute rejection in lung
      transplants.

PMID- 9159617
TI  - Esophagogastrectomy for carcinoma of the esophagus and cardia: a comparison of
      findings and results after standard resection in three consecutive eight-year
      intervals with improved staging criteria.
AB  - OBJECTIVE: A review of findings and results after standard resection for
      carcinoma of the esophagus and cardia without neoadjuvant therapy was done to
      provide a basis for comparison with current reports of radical resection and
      neoadjuvant therapy. METHODS: A 24-year experience on one surgical service with
      454 operations for carcinoma of the esophagus and cardia was reviewed. A
      comparison of findings and results in three consecutive 8-year intervals was
      analyzed, and new staging criteria were developed and compared with those
      currently favored by the American Joint Committee on Cancer. RESULTS: From
      January 1, 1970, to January 1, 1994, 454 patients with carcinoma of the esophagus
      or cardia underwent operation, of whom 408 (90%) had esophagogastrectomy with a
      30-day mortality rate of 2.5% and an additional hospital mortality rate of 1.2%.
      Of the 121 complications (30.7%), 71 (18%) were major and 50 (12.7%) were minor.
      Cardiovascular complications predominated. The overall 5-year survival was 24.7%,
      with a 33.7% survival after complete resections in the most recent interval under
      study. Palliation of dysphagia was achieved in nearly 80% of patients who
      survived the operation. During the three intervals under review, resectability,
      mortality, and complication rates remained constant. The percentages of left
      thoracotomies and transhiatal resections increased, and there was a decrease in
      thoracoabdominal incisions. The percentages of patients with Barrett's esophagus
      and stage 0 and I tumors increased. The percentage of complete resections (R0)
      increased, whereas that for resections with residual microscopic tumor (R1)
      decreased, and there was no change in the percentage of patients with residual
      gross tumor after resection (R2). Modified WNM staging criteria are proposed that
      provide better prognostic stratification of the disease than those currently
      favored by The American Joint Committee on Cancer. CONCLUSIONS: Standard
      esophagogastrectomy is applicable in 90% of patients with operable carcinoma of
      the esophagus or cardia, with consistently low mortality and morbidity rates and
      satisfactory palliation of dysphagia. The 5-year survival (24.7% overall) remains
      suboptimal, but the current figure for complete resections (33.7%) is
      encouraging. There is a need for revision of the current American Joint Committee
      on Cancer staging criteria.

PMID- 9159618
TI  - Nitric oxide improves pulmonary vascular impedance, transpulmonary efficiency,
      and left ventricular filling in chronic pulmonary hypertension.
AB  - OBJECTIVE: Chronic pulmonary hypertension is difficult to treat and despite the
      introduction of several therapeutic options, no single therapy is universally
      recommended. Nitric oxide has had some role clinically in improving pulmonary
      hemodynamics in this setting; however, basic investigation has not been performed
      in an appropriate large animal model of stable pulmonary hypertension. This study
      was designed to examine the effects of inhaled nitric oxide on pulmonary
      hemodynamics in the setting of a canine model of monocrotaline pyrrole-induced
      chronic pulmonary hypertension and used Fourier analysis for assessment of
      pulmonary vascular impedance. METHODS: Sixteen mongrel dogs (22 to 25 kg) were
      used. Animals underwent percutaneous pulmonary artery catheterization to measure
      right-sided hemodynamics before and 6 weeks after a right atrial injection of
      either monocrotaline pyrrole (n = 8) or placebo (n = 8). Six weeks after the
      injection all hearts were instrumented with an ultrasonic flow probe,
      sonomicrometric dimension transducers, and micromanometers. Data were collected
      at baseline and after nitric oxide administration. Harmonic derivation of
      functional data was achieved with Fourier analysis. RESULTS: Six weeks after the
      injection, significant increases in pulmonary artery pressure and pulmonary
      vascular resistance were observed in the monocrotaline pyrrole group. Nitric
      oxide led to significant decreases in pulmonary vascular impedance. Significant
      improvements in pulmonary blood flow, transpulmonary efficiency, and left
      ventricular filling were also observed. CONCLUSIONS: This investigation
      demonstrates the well-known clinical effects of nitric oxide in improving
      pulmonary hypertension, which were also associated with an increase in pulmonary
      blood flow, transpulmonary efficiency, and left ventricular filling in the
      setting of monocrotaline pyrrole-induced pulmonary hypertension.

PMID- 9159619
TI  - One-stage complete unifocalization in infants: when should the ventricular septal
      defect be closed?
AB  - BACKGROUND: The decision whether to close the ventricular septal defect at the
      time of unifocalization in patients with pulmonary atresia, ventricular septal
      defect, and major aortopulmonary collaterals may be difficult. The purpose of
      this study was to develop morphologic and physiologic methods to aid in deciding
      whether to close the ventricular septal defect in patients undergoing one-stage
      unifocalization. METHODS: Between July 1992 and April 1996, 27 infants with
      pulmonary atresia, ventricular septal defect, and aortopulmonary collaterals were
      treated at our institution. Midline complete unifocalization was performed in 25
      patients-the ventricular septal defect was closed in 17 and left open in eight.
      Two patients with severe distal collateral stenoses underwent staged
      unifocalization. Pulmonary artery and collateral sizes were measured from
      preoperative angiograms and used to calculate the indexed cross-sectional area of
      the total neopulmonary artery bed. An intraoperative pulmonary flow study
      previously validated with experiments in neonatal lambs was performed in six
      patients: the unifocalized neopulmonary arteries were perfused with a known flow
      and pulmonary artery pressures were recorded. RESULTS: The neopulmonary artery
      index was greater in patients who underwent ventricular septal defect closure
      than in those who did not (p = 0.001), although the values did overlap. This
      index correlated with the postoperative right ventricular/left ventricular
      pressure ratio (p = 0.037). Mean pulmonary artery pressures obtained during the
      intraoperative flow study and after bypass were comparable. CONCLUSION: The total
      neopulmonary artery index correlates with postrepair right ventricular/left
      ventricular pressure ratio and is useful in deciding when to close the
      ventricular septal defect if it is larger than 200 mm2/m2. The pulmonary flow
      study is helpful in deciding whether to close the ventricular septal defect in
      all patients.

PMID- 9159620
TI  - Long-term follow-up of truncus arteriosus repaired in infancy: a twenty-year
      experience.
AB  - BACKGROUND: There have been few reports of long-term follow-up after truncus
      arteriosus repair in infancy. METHODS: A retrospective review was performed to
      assess long-term outcomes among 165 patients who survived the initial hospital
      stay after complete repair of truncus arteriosus since 1975. The median age at
      truncus repair over this 20-year experience was 3.5 months (range 2 days to 36
      years), and 81% of patients were less than 1 year of age. Previous pulmonary
      artery banding had been performed in 15 patients, and two patients had undergone
      prior repair of interrupted aortic arch. Significant procedures performed along
      with truncus repair included truncal valve replacement (n = 10) or repair (n = 5)
      and repair of interrupted aortic arch (n = 4). RESULTS: Patients were followed up
      for up to 20.4 years (median 10.5 years). Twenty-five patients were lost at cross
      sectional follow-up, with a total of 67 patient-years of follow-up available on
      these patients. There have been 23 late deaths, eight of which occurred within 6
      months of repair and 13 of which occurred within 1 year. Ten of the late deaths
      were related to reoperations. Actuarial survival among all hospital survivors was
      90% at 5 years, 85% at 10 years, and 83% at 15 years and was essentially
      identical for infants alone. A significant independent risk factor for poorer
      long-term survival was truncus with moderate to severe truncal valve
      insufficiency before repair. During the follow-up period, 107 patients underwent
      133 conduit reoperations. Median time to conduit reoperation was 5.5 years, and
      the only factor significantly associated with shorter time to conduit replacement
      was smaller conduit size at initial repair. In addition, 26 patients underwent 30
      truncal valve replacements. Six patients required truncal valve replacement
      before any conduit-related reintervention, with two associated deaths. Actuarial
      freedom from truncal valve replacement among patients with no prerepair truncal
      valve insufficiency was 95% at 10 years. Actuarial freedom from truncal valve
      replacement was significantly lower among patients with truncal insufficiency
      before initial repair (63% at 10 years). At follow-up, all patients except three
      were in New York Heart Association functional class I. CONCLUSIONS: Ten- to 20
      year survival and functional status are excellent among infants undergoing
      complete repair of truncus arteriosus. Conduit replacement or revision is almost
      inevitably necessary in this group of patients.

PMID- 9159621
TI  - Regenerative healing of incisional wounds in midgestational murine hearts in
      organ culture.
AB  - OBJECTIVE: Using an organ-culture fetal heart repair model, we explored fetal
      repair in tissues other than dermis. METHODS: Wounded fetal mouse hearts of 14
      and 18 days' gestation (term = 20 days), as well as hearts of 22 days' gestation
      (newborn), were maintained in serum-free medium. Specimens were fixed at 2, 7,
      and 11 days and then processed for histologic examination. Small fragments of
      fetal hearts from all time points were cultured as explants. The migration of
      cells from the periphery of the explants was compared at day 4, and the pattern
      of microfilaments in these cells was assessed. RESULTS: In 14-day hearts (n =
      18), tissue architecture was rapidly reestablished without an inflammatory
      response or scarring, constituting regenerative repair. In 18-day hearts (n =
      18), no reestablishment of muscle fibers or wound closure occurred. In the 22-day
      explants (n = 12) the wounds closed by scarring. Cell migration from 14-day
      explants was 4.7 +/- 2.3 ocular units; from 18-day explants, it was 2.6 +/- 1.1
      ocular units; and from 22-day explants, it was 0.9 +/- 0.4 ocular units.
      Microfilaments of 14-day cells were arranged at the periphery of the cell
      consistent with cardiomyocytes. Microfilaments of 18- and 22-day cells were
      arranged in parallel arrays (stress fibers) that were consistent with
      fibroblasts. CONCLUSIONS: We propose that regenerative healing of 14-day fetal
      hearts is by the migration of cardiomyocytes. At 18 and 22 days, cardiomyocytes
      are too differentiated and unable to migrate; hence cell migration is limited to
      resident fibroblasts, which are deficient at 18 days but sufficient at 21 days to
      be repaired by the scarring process.

PMID- 9159622
TI  - Delayed sternal closure after cardiac operations in a pediatric population.
AB  - OBJECTIVE: The purpose of this study was to assess morbidity and mortality
      associated with delayed sternal closure after pediatric cardiac operations.
      METHODS: Hospital records were reviewed of all patients with an open sternum
      after a cardiac operation at Children's Hospital, Boston, from January 1992 to
      December 1995. RESULTS: A total of 178 patients had delayed sternal closure with
      an overall mortality rate of 19%. The most common diagnosis of patients with
      delayed sternal closure was hypoplastic left heart syndrome (29%). Although
      myocardial distention or chest wall edema (n = 47) was a common indication to
      delay sternal closure, in many patients (n = 47) the sternum was left open
      electively to avoid postoperative cardiac or respiratory compromise. Successful
      sternal closure was achieved in 158 patients (89%) at a mean of 3.4 +/- 1.8 days
      after opening. There were significant increases in left atrial pressure (7.7 +/-
      3.4 to 9.8 +/- 4.1 mm Hg, p = 0.00001) and right atrial pressure (8 +/- 3.2 to
      10.1 +/- 3.3 mm Hg, p = 0.00001) with sternal closure. There was a small but
      statistically significant drop in pH (7.44 +/- 0.05 to 7.41 +/- 0.08, p < 0.0001)
      during sternal closure. The peak inspiratory pressure, delivered breaths per
      minute, and fraction of inspired oxygen all significantly increased during
      sternal closure. Clinical evidence of surgical site infection occurred in 12
      (6.7%) of the patients with delayed sternal closure; mediastinitis developed in 7
      (3.9%) patients. CONCLUSIONS: Although delayed sternal closure after complex
      operations for congenital heart disease is often necessary in the operating room
      because of edema, unstable hemodynamic conditions, or bleeding, it can also be
      used electively to aid in hemodynamic and respiratory stability in the initial
      postoperative period. Our review supports a low morbidity associated with delayed
      sternal closure in a pediatric population.

PMID- 9159623
TI  - Pulmonary autograft versus homograft replacement of the aortic valve: a
      prospective randomized trial.
AB  - BACKGROUND: Pulmonary autografts offer many theoretical advantages. However, the
      operation is complex, may interfere with right ventricular and pulmonary outflow
      function, and requires a longer operative time than does the homograft operation.
      The effects of these potential disadvantages are unknown. METHODS: To clarify
      these issues we randomized 70 patients undergoing aortic valve replacement to an
      aortic homograft group (group A = 37 patients; 53%; 34 male, 3 female) or a
      pulmonary autograft group (group B = 33 patients; 47%; 28 male, 5 female). Ages
      varied from 12 to 65 years (mean 39 +/- 15 years) for group A and from 3 to 54
      years (mean 29 +/- 15 years) for group B (p = not significant). Eleven patients
      in group A (30%) and eight in group B (24%) had previous aortic valve surgery.
      All patients were operated on by the same surgeon. The mean cardiopulmonary
      bypass time was 113 +/- 29 minutes (range 66 to 175 minutes) for group A and 151
      +/- 31 minutes (range 115 to 226 minutes) for group B (p < 0.002). Mean aortic
      crossclamp time was 85 +/- 19 minutes (range 45 to 140 minutes) for group A and
      109 +/- 20 minutes (range 74 to 164 minutes) for group B (p = 0.02). In 32
      patients (86.5%) the aortic homograft was implanted as a root with coronary
      reimplantation. All pulmonary autografts were implanted as a root. RESULTS: No
      early or late deaths had occurred in this series at a mean follow-up time of 16
      months (range 3 to 21 months). Two patients (one in each group) required
      reexploration for bleeding. No statistically significant differences were
      observed between the two groups with regard to ventilatory support (group A, mean
      10 +/- 8.5 hours; group B, mean 29 +/- 85 hours), total blood loss (group A, mean
      471 +/- 347 ml; group B, mean 543 +/- 404 ml), intensive care unit stay (group A,
      mean 1.2 +/- 0.6 days; group B, mean 2 +/- 3.7 days), and hospital stay (group A,
      mean 9.5 = 3.2 days; group B, mean 12 +/- 6 days). Postoperatively, all patients
      are in New York Heart Association class I (93%) or II (7%) (p = not significant).
      Ejection fraction for the two groups did not change significantly over the follow
      up period. Left ventricular mass and diastolic diameter showed progressive
      regression, with no apparent difference between the two treatment groups to date.
      Echocardiographic evaluation of aortic valve function at 6 months showed good
      valve function in all patients with no evidence of aortic regurgitation in 80% of
      both groups. In group B the right ventricular outflow gradient was below 15 mm Hg
      over the follow-up period. Holter monitoring, available only in 44 patients
      (63%), showed most of the arrhythmias to be grade 0 to 1 of the modified Lown
      grading system. CONCLUSION: Although the pulmonary autograft requires a
      significantly longer operating time, this does not seem to affect early and
      medium-term outcome when compared with results obtained with aortic homografts.
      Continued patient evaluation is warranted, particularly with regard to evidence
      of valve degeneration and right ventricular function and arrhythmias in the long
      term.

PMID- 9159624
TI  - Extent and pattern of regression of left ventricular hypertrophy in patients with
      small size CarboMedics aortic valves.
AB  - OBJECTIVE: To assess the extent and pattern of regression of left ventricular
      hypertrophy after valve replacement for aortic stenosis, we studied 26 patients
      receiving either 19 or 21 mm CarboMedics valves (group I, 13 patients) or either
      23 or 25 mm CarboMedics valves (group II, 13 patients). The studies were done
      before the operation and after 3 years, and results were compared with those of
      10 control patients. METHODS: Left ventricular end-diastolic and end-systolic
      diameters and volumes, ejection fraction and fractional shortening, and
      interventricular septum and posterior wall thickness were measured. The ratio
      between interventricular septum and posterior wall thickness, the ratio between
      left ventricular wall thickness and left ventricular chamber radius, and the left
      ventricular mass were then calculated. RESULTS: At follow-up there was a
      significant reduction in the left ventricular mass, interventricular septum, and
      posterior wall thickness for both patient groups (p < 0.01). However, only the
      posterior wall thickness reached normal values; the interventricular septum and
      the left ventricular mass indices were still significantly greater than in the
      control group (p < 0.01). Because of the incomplete regression of
      interventricular septal hypertrophy, the ratio between interventricular septum
      and posterior wall thickness was similar between both patient groups but it was
      significantly higher than in control subjects (p < 0.01). The ratio between wall
      thickness and chamber radius did not decrease significantly in group II patients,
      in whom it remained above the control values. CONCLUSION: Having a bileaflet
      aortic prosthesis of one size larger did not seem to significantly influence the
      pattern and the extent of regression of left ventricular hypertrophy after an
      intermediate period of follow-up.

PMID- 9159625
TI  - Low-intensity oral anticoagulation plus low-dose aspirin versus high-intensity
      oral anticoagulation alone: a randomized trial in patients with mechanical
      prosthetic heart valves.
AB  - BACKGROUND: Mechanical heart valve replacement requires lifelong anticoagulant
      treatment. Aspirin has proved useful in further reducing thromboembolic events
      when added to oral anticoagulants. However, increased (gastrointestinal) bleeding
      was observed at the doses previously tested for this combination in heart valve
      prostheses. METHODS: We performed a prospective randomized trial to compare the
      combination of low-intensity oral anticoagulants (international normalized ratio
      2.5 to 3.5) plus aspirin (100 mg/day) (arm A) versus high-intensity oral
      anticoagulants alone (arm B) (international normalized ratio 3.5 to 4.5). Arm A
      included 258 patients and arm B 245 patients. The two groups were comparable for
      all baseline characteristics. RESULTS: The outcomes of the study were embolism,
      valve thrombosis, and major hemorrhage. The median follow-up was 23 months. The
      two treatments offered similar antithrombotic protection. The incidence of
      embolic episodes was 1.32 per 100 patient-years (95% confidence interval 0.53 to
      2.7) for arm A and 1.48 per 100 patient-years (95% confidence interval 0.59 to
      3.03) for arm B. Major hemorrhage occurred in 1.13 per 100 patient-years (95%
      confidence interval 0.41 to 2.45) for arm A and 2.33 per 100 patient-years (95%
      confidence interval 1.17 to 4.14) for arm B. Gastrointestinal bleeding was not
      increased by this combined reduced dose of aspirin and coumarin.

PMID- 9159626
TI  - Retrograde cardioplegia preserves myocardial function after induced coronary air
      embolism.
AB  - Coronary air embolism is a potential complication of cardiopulmonary bypass. We
      compared left ventricular function before and after the administration of
      antegrade or retrograde cardioplegic solution in a porcine model of coronary air
      embolism. Nineteen pigs were placed on cardiopulmonary bypass support and cooled
      to 32 degrees C. The heart was initially arrested with antegrade cold blood
      cardioplegic solution. The aortic crossclamp was released at 30 minutes and 0.02
      cc/kg body weight of air was injected into the left anterior descending artery
      distal to the first diagonal branch. After 5 minutes the aorta was reclamped and
      the animals treated with 15 ml/kg body weight of 1:4 blood cardioplegic solution
      delivered by the antegrade (n = 6) or retrograde (n = 7) method. Control animals
      (n = 6) were not treated. Changes in regional preload recruitable stroke work
      were used to assess left ventricular performance before and after cardiopulmonary
      bypass. Two control animals could not be weaned from cardiopulmonary bypass. Left
      ventricular function was best preserved after treatment of induced coronary air
      embolism with retrograde cardioplegia (90% of baseline). Coronary air embolism
      treatment with antegrade cardioplegia resulted in diminished left ventricular
      performance (68% of baseline). In control animals left ventricular contractility
      was significantly impaired (39% of baseline). We conclude that administration of
      retrograde cardioplegic solution may be an effective method of treating coronary
      air embolism. The favorable outcome seen with cardioplegia may be in part because
      of its ability to protect the ischemic myocardium while the solution mechanically
      dislodges air from the vascular bed.

PMID- 9159627
TI  - Dynamic cardiac compression improves contractile efficiency of the heart.
AB  - The effect of dynamic cardiac compression on left ventricular contractile
      efficiency was assessed in terms of the pressure-volume relationship and
      myocardial oxygen consumption. In 11 excised cross-circulated dog hearts, the
      ventricle was directly compressed during systole (dynamic cardiac compression).
      Measurements for pressure-volume area (a measure of total mechanical energy),
      external work, and myocardial oxygen consumption were done before and during
      dynamic cardiac compression. Dynamic cardiac compression increased pressure
      volume area by 28% +/- 17% (mean plus or minus the standard deviation) and
      external work by 24% +/- 20% (p = 0.0000185 and 0.0000212, respectively) at given
      end-diastolic and stroke volumes without affecting myocardial oxygen consumption.
      As a result, the oxygen cost of pressure-volume area, that is, the slope of the
      myocardial oxygen consumption-pressure-volume area relationship, significantly
      decreased by 16% +/- 13% (p = 0.0000135) whereas the pressure-volume area
      independent myocardial oxygen consumption was unchanged. Then, contractile
      efficiency, that is, the reciprocal of the slope of the myocardial oxygen
      consumption-pressure-volume area relationship in joules significantly improved
      from 45% +/- 8% to 53% +/- 13% (p = 0.0000437). When the native myocardial oxygen
      consumption-pressure-volume area relationship was assessed by subtracting the
      dynamic cardiac compression pressure applied to the heart, the slope of the
      myocardial oxygen comsumption-pressure-volume area relationship returned to the
      control level. This indicates that the contractile efficiency of the native heart
      was not affected by dynamic cardiac compression. We conclude that dynamic cardiac
      compression enhances left ventricular pump function by improving the contractile
      efficiency of the overall heart leaving the energetics of the native heart
      unchanged.

PMID- 9159628
TI  - Depolarizing cardiac arrest and endothelium-derived hyperpolarizing factor
      mediated hyperpolarization and relaxation in coronary arteries: the effect and
      mechanism.
AB  - OBJECTIVES: Depolarizing (hyperkalemic) solutions are widely used to preserve
      organs for transplantation and for cardiac operations. We previously observed
      that exposure to hyperkalemia reduced endothelium-dependent, noncyclooxygenase-
      and non-nitric oxide-mediated relaxation. This study was designed to examine the
      mechanism of this effect with regard to K channels and the associated membrane
      potential changes. METHODS: Porcine coronary artery rings were studied in organ
      chambers. After incubation of the tissue with 20 or 50 mmol/L doses of potassium
      for 1 hour, the endothelium-derived hyperpolarizing factor-mediated relaxation in
      the artery and the membrane hyperpolarization in a single coronary smooth muscle
      cell were studied. RESULTS: The endothelium-derived hyperpolarizing factor
      mediated relaxation induced by substance P, which could be significantly
      inhibited by the Ca(2+)-activated K channel blocker tetraethylammonium but only
      to a lesser extent by the adenosine triphosphate-sensitive K channel blocker
      glibenclamide, was significantly reduced. Substance P-induced hyperpolarization
      of the membrane potential was also significantly reduced by the hyperkalemic
      incubation with a significantly elevated resting membrane potential. CONCLUSIONS:
      Depolarizing arrest reduces endothelium-derived hyperpolarizing factor-mediated
      membrane hyperpolarization and relaxation by affecting mainly the Ca(2+)
      activated K channels and by depolarizing the membrane for a prolonged period. We
      suggest that this is one of the mechanisms for coronary dysfunction after
      exposure to depolarizing (hyperkalemic) cardioplegic and organ-preservation
      solutions and that, therefore, "perfect" protection of the heart or other organs
      should restore the endothelium-derived hyperpolarizing factor-related endothelial
      function.

PMID- 9159629
TI  - Effect of preoperative supplementation with alpha-tocopherol and ascorbic acid on
      myocardial injury in patients undergoing cardiac operations.
AB  - Augmentation of antioxidant defenses may help protect tissues against ischemia
      reperfusion injury associated with operations involving cardiopulmonary bypass.
      In this study we examined the effect of pretreating patients with alpha
      tocopherol (vitamin E) and ascorbic acid (vitamin C) or placebo on injury to the
      myocardium. Seventy-six subjects undergoing elective coronary artery bypass
      grafting participated in a prospective, double-blind, placebo-controlled
      randomized trial, receiving either placebo or both 750 IU dl-alpha-tocopherol per
      day for 7 to 10 days and 1 gm ascorbic acid 12 hours before the operation. Plasma
      alpha-tocopherol concentrations, raised fourfold by supplementation, fell by 70%
      after the operation in the supplemented group and to negligible levels in the
      placebo group. There were no significant differences between the groups with
      respect to release of creatine kinase MB isoenzyme over 72 hours, nor in the
      reduction of the myocardial perfusion defect determined by thallium 201 uptake.
      Electrocardiography provided no evidence of a benefit from antioxidant
      supplementation. Thus the supplementation regimen prevented the depletion of the
      primary lipid soluble antioxidant in plasma, but provided no measurable reduction
      in myocardial injury after the operation.

PMID- 9159630
TI  - Bilateral minimally invasive direct coronary artery bypass grafting with the use
      of two arterial grafts.

PMID- 9159631
TI  - Migration of implantable cardioverter-defibrillator patch into the right atrium.

PMID- 9159632
TI  - S-100 protein release in a range of cardiothoracic surgical procedures.

PMID- 9159633
TI  - Platypnea and orthodeoxia: shunting associated with an aortic aneurysm.

PMID- 9159634
TI  - The role of annuloplasty in mitral valve repair.

PMID- 9159635
TI  - Pedicled pericardial flaps.

PMID- 9159636
TI  - Transmanubrial approach to the thoracic inlet.

PMID- 9159637
TI  - Endorsement for sparing the clavicle in the transcervical approach to the
      thoracic inlet.

PMID- 9159638
TI  - Coronary arteries arising from the contralateral aortic sinus: electron beam
      computed tomographic demonstration of the initial course of the artery with
      respect to the aorta and the right ventricular outflow tract.

PMID- 9159639
TI  - Potassium transport and potassium channels in the kidney tubules.
AB  - A variety of K+ channels have been identified using electrophysiological
      techniques including the patch-clamp method. The types of channels include
      inwardly-rectifying, ATP-dependent, Ca(2+)-dependent, voltage-gated, and so on.
      Some of them have been cloned by expression and/or PCR cloning techniques, which
      give us their amino-acid sequences and molecular topology in the cell membrane.
      Immunohistochemical studies have shown the proteins (channels) to be localized to
      the luminal and/or basolateral membranes of a certain nephron segment. However,
      the relationships of these proteins with the ionic channels identified
      functionally must be examined by their reconstitution in cell-free systems (lipid
      bilayer membrane) and/or their expression in cells lacking native K+ channels.
      Much more care should also be taken to avoid artifacts due to channel-inducing
      factors (CHIF). Structure-function studies at the molecular level will advance
      our knowledge of the renal K+ channels and provide us with a further
      understanding of the role of the kidney in K+ homeostasis.

PMID- 9159640
TI  - Inwardly rectifying potassium channels: their molecular heterogeneity and
      function.
AB  - A variety of cells including cardiac myocytes and neuronal cells possess inwardly
      rectifying K+ (Kir) channels through which currents flow more readily in the
      inward direction than outward. These K+ channels play pivotal roles in
      maintenance of the resting membrane potential, in regulation of the action
      potential duration, in receptor-dependent inhibition of cellular excitability,
      and in the secretion and absorption of K+ ions across cell membrane. Recent
      molecular biological dissection has shown that the DNAs encoding Kir channels
      constitute a new family of K+ channels whose subunits contain two putative
      transmembrane domains and a pore-forming region. So far, more than ten cDNAs of
      Kir channel subunits have been isolated and classified into four subfamilies: 1)
      IRK subfamily (IRK1-3/Kir1.1-1.3), 2) GIRK subfamily (GIRK1-4/Kir3.1-3.4), 3) ATP
      dependent Kir subfamily (ROMK1/Kir1.1, K(AB)-2/Kir4.1), and 4) ATP-sensitive Kir
      subfamily (uKATP-1/Kir6.1, BIR/Kir6.2). Xenopus oocytes injected with the cRNAs
      of IRKs elicit classical Kir channel currents. GIRKs, as heteromultimers, compose
      the G protein-gated Kir (KG) channels, which are regulated by a variety of Gi/Go
      coupled inhibitory neurotransmitter receptors such as m2-mus-carinic,
      serotonergic (5HT1A), GABAB, somatostatin and opioid (mu, delta, kappa)
      receptors. ROMK1 and KAB-2 are characterized with a Walker type-A ATP-binding
      motif in their carboxyl termini, and may be involved in K+ transport in renal
      epithelial and brain glial cells. uKATP-1 and BIR form with sulfonylurea
      receptors, the so-called ATP-sensitive K+ channels. Thus, it is a feature of the
      Kir channel family that each subfamily plays a specific physiological functional
      role. The (Na+)-activated Kir channels identified electrophysiologically in
      neurons and cardiac myocytes have not yet been cloned. In this review, we
      overviewed the current understandings of the features of the molecular structures
      and functions of the four main subfamilies of Kir channels.

PMID- 9159641
TI  - Changes in intracellular Ca2+ concentration produced by the alteration of
      intracellular pH in rat parotid acinar cells.
AB  - The effects of intracellular pH (pH(i)) on intracellular Ca2+ concentration
      ([Ca2+]i) vary in different cells, and mechanisms underlying these effects are
      still not clear. In the experiments reported here, the effects of changes in
      pH(i) produced by ammonium chloride and butyric acid were studied in
      enzymatically dispersed acinar cells of rat parotid glands. The changes in pH(i)
      and [Ca2+]i were estimated using the fluorescent dyes biscarboxyethyl-5,6
      carboxyfluorescein (BCECF) and fura-2, respectively. pH(i) was altered using
      NH4Cl, butyric acid, or propionic acid while keeping the external pH constant at
      7.4. NH4Cl (20 mM) applied for 4-5 min increased pH(i) from 7.18 to 7.79 (a
      decrease of proton concentration, [H+]i, from 66 to 16 nM) and produced a
      transient [Ca2+]i increase followed by a small sustained decrease. On the other
      hand, butyric acid (20 mM) decreased pH(i) from 7.16 to 6.81 (an increase of
      [H+]i from 69 to 155 nM) and produced a small sustained increase in [Ca2+]i.
      Washing out the butyric acid 4 min after application induced the recovery of
      pH(i) from 6.93 to 7.43 (a decrease of [H+]i from 118 to 37 nM) and a further
      transient increase in [Ca2+]i. The removal of external Ca2+ had little effect on
      changes in pH(i) produced by NH4Cl or butyric acid, but markedly reduced both the
      sustained and transient components of [Ca2+]i response. Cyclopiazonic acid (0.3
      microM), an inhibitor of Ca2+ pump in intracellular stores, abolished the
      transient [Ca2+]i increase produced by the application of NH4Cl or withdrawal of
      butyric acid. These results suggest that a decrease in [H+]i, not the absolute
      level of [H+]i may release Ca2+ from intracellular stores.

PMID- 9159642
TI  - Effects of exposure to hypobaric-hypoxia on body weight, muscular and
      hematological characteristics, and work performance in rats.
AB  - The metabolic activities of skeletal muscles were studied in male rats exposed to
      hypobaric-hypoxia at about 550 Torr for 8 h per day for 2 weeks. Rats were
      divided into three groups; control (normoxic control), diurnal hypoxic (DH)
      exposure, and nocturnal hypoxic (NH) exposure groups. The changes in body weight
      and daily diet intake of the NH group were lower than the other groups (p <
      0.01). The weights of fat in the abdominal cavity of both NH and DH groups were
      less than that of the control group. The red blood cell count, hemoglobin
      concentration, and hematocrit values were significantly increased in the hypoxic
      groups. The plasma glucose level in the NH group was significantly less than the
      control group (p < 0.05). The lactate dehydrogenase/citrate synthase (LDH/CS)
      activity ratios in the skeletal muscle tended to be lower in both hypoxic groups
      than in the control group. The swimming times to exhaustion at mild and high
      intensities that were measured after 2 weeks, loaded with a weight equivalent to
      2.5% of the body weight, improved in the DH group. There were insignificant
      differences in the metabolic activity of skeletal muscles and blood
      characteristics between the NH and DH groups, but endurance swimming times in the
      DH group tended to be improved as compared to the NH group. We conclude that the
      DH group became competent in endurance work, which is believed to be driven from
      the combined effects of increased O2 transport capacity of the blood and enhanced
      O2 utilization capability by mitochondrial enzyme activity.

PMID- 9159643
TI  - Respiratory responses to passive and active recovery from exercise.
AB  - To investigate the effect of the neural components associated with leg movements
      on the control of ventilation during recovery from exercise, we recorded the
      minute ventilation (VE), oxygen uptake (VO2), and carbon dioxide output (VCO2) of
      eight normal volunteers during recovery from moderate, steady-state cycle
      exercise (170 W). The recovery phases were undergone separately under two
      different conditions: 5 min of rest (passive recovery) on a bicycle ergometer and
      3 min of pedaling at a work rate of 0W (active recovery) followed by 2 min of
      rest. The phase-1 responses were observed in all the variables studied at the
      transition of passive recovery but not in the active recovery phase. The kinetics
      of VCO2, during the off-transition were significantly faster than those of VE in
      both recoveries, indicating that the decreases in VCO2 could precede the
      decreases in VE. Although the levels of VE and VCO2 during active recovery were
      significantly higher than those during passive recovery, the decline in VE was
      closely proportional to that of VCO2 under both recovery conditions, with
      resultant indications of similar VE-VCO2 regression lines. These findings suggest
      that the flux of CO2 to the lungs is an important determinant of ventilatory
      drive during recovery, and that neither central command nor neural afferents from
      contracting muscles are requisite for the control of ventilation during recovery
      from exercise.

PMID- 9159644
TI  - The G alpha protein GL2 alpha improves the ability to detect the subthreshold
      expressions of receptors linked to phospholipase C in Xenopus oocytes.
AB  - Xenopus laevis oocytes showed no electrophysiological responses to acetylcholine
      (ACh) and had no significant cholinergic receptor sites when prepared under our
      conditions. However, they were found to acquire robust electrophysiological
      responsiveness to ACh when bovine GL2 alpha, which is a member of the Gq alpha
      family and is highly homologous to mouse G11 alpha, was expressed by mRNA
      injection. Further analyses indicated that GL2 alpha amplified the activity of
      endogenous muscarinic ACh receptors that are expressed at an otherwise
      undetectable level, and thus made their detection possible. Thus, GL2 alpha may
      prove to be an effective method for detecting the activities of phospholipase C
      linked receptors which are only marginally expressed. The usefulness of this
      method was confirmed in the analyses of a chimeric receptor constructed from
      metabotropic glutamate receptor subtype 1 alpha and muscarinic ACh receptor
      subtype M1. The chimeric receptor showed no electrophysiological responses to ACh
      when expressed alone in oocytes, but became responsive to ACh when co-expressed
      with GL2 alpha.

PMID- 9159645
TI  - Temperature dependence of the inward rectifier K+ channel gating in guinea-pig
      ventricular cells.
AB  - Whole-cell and single-channel currents of the inward rectifier K+ channels from
      guinea-pig ventricular myocytes were recorded over the range between 5 and 37
      degrees C. The conductance for inward currents was decreased by lowering the
      temperature with a Q10 of 1.28 (whole cell), or 1.41 (single channel) between 20
      and 30 degrees C. The open probability of the channel at -100 mV remained high (>
      0.9). The distribution of open times was single exponential at all temperatures,
      confirming a single open state. The entropy change (delta S) for the closing rate
      of the channel obtained from open-time distribution was -14.0 e.u. (cal/mol/K),
      and enthalpy change (delta H) was 11.9 kcal/mol. The configuration of closed-time
      distribution varied markedly by altering the temperature, and three exponentials
      were necessary to fit the histogram. The slowest component showed higher
      temperature dependency (delta S = 13.6 e.u. and delta H = 19.0 kcal/mol) than the
      other two faster components. By assuming a reduced model of C-O at 37 degrees C,
      the difference in Gibb's free energy (GOC) between the open and closed states was
      approximately 2 kcal/mol, and the height of the energy barrier for the C-O
      transition was estimated to be approximately 15 kcal/mol.

PMID- 9159646
TI  - Electromyographic (EMG) study of cold shivering in the chronic spinal dog.
AB  - Cold shivering in six chronic spinal dogs (T9-10), which became capable of weight
      bearing standing and/or walking with their hindlimbs, was studied by
      electromyography (EMG). In the forequarters, EMG activities in the form of
      grouping discharges (GD) accompanied by visible tremor (VT) were induced at an
      ambient temperature of 15 degrees C in all the dogs. In the hindquarters, GD with
      VT were induced at 3 degrees C in one dog. Although GD with VT were not induced
      in in the remaining dogs, GD without VT were produced by additional cutaneous
      stimuli to the hindquarters at 3 degrees C. These stimuli never produced GD in
      the hindquarters at room temperature. Though the mean frequency of GD in the
      hindquarters was lower than that in the forequarters, the range of the frequency
      in the hindquarters was much the same as that in the forequarters. During the
      experiment, the drop in rectal temperature was less than 0.6 degrees C in all of
      the dogs. These findings suggest that the chronically isolated spinal cord is
      responsible for cold shivering, while its excitability to cold exposure is less
      than that of the spinal cord governed by the supraspinal center.

PMID- 9159647
TI  - No suppression of respiratory function of mitochondrial isolated from the hearts
      of anesthetized rats with high-dose pentobarbital sodium.
AB  - Pentobarbital sodium is a widely used anesthetic for animal experiments. We have
      already reported that a high dose of pentobarbital sodium (100 mg/kg i.p., twice
      the usual anesthetic dose) depresses myocardial mechanoenergetics in the canine
      heart. Furthermore, it has been reported that a high concentration of
      pentobarbital sodium inhibits myocardial contractility and mitochondrial electron
      transport and energy transfer. Therefore, we were afraid that the mitochondrial
      respiratory function would be impaired by pentobarbital anesthesia and that
      pentobarbital sodium would be an inappropriate anesthetic for cardiac
      mechanoenergetic studies. In this study, we investigated the respiratory function
      of mitochondria isolated from the hearts of anesthetized rats with high-dose
      pentobarbital sodium. We examined the mitochondrial respiratory function by the
      ADP/O ratio, respiratory control index (RCI), oxygen consumption rate in state
      III (State III O2) by oximetry, and membrane potential using a fluorescent dye,
      3,3'-dipropylthiodicarbocyanine iodide (diS-C3-(5). The ADP/O ratio, RCI, and
      State III O2 values and changes in membrane potential induced by various
      respiratory substances were not significantly different between the rats with and
      without anesthesia. These results indicate that the respiratory function is not
      suppressed in the isolated myocardial mitochondria of rat hearts after high-dose
      pentobarbital anesthesia, although the pentobarbital sodium blood concentration
      was of the same order as that which exerts mitochondrial uncoupling in rat
      isolated mitochondrial preparation. Therefore, pentobarbital sodium anesthesia up
      to 100 mg/kg i.p. is applicable for mechanoenergetic studies of excised rat
      hearts, at least from the energetic aspect.

PMID- 9159648
TI  - Activated macrophage-mediated endogenous prostaglandin and nitric oxide-dependent
      relaxation of lymphatic smooth muscles.
AB  - The effects of macrophages activated by bacterial lipopolysaccharides (LPS) on
      the mechanical activity of lymph vessels with or without the endothelium were
      investigated using conventional bioassay preparations. Rat peritoneal macrophages
      emigrated by an injection of thioglycollate were isolated and cultured for 12 h
      in RPMI 1,640 medium containing 10 micrograms/ml LPS. More than 97% of the
      cultured cells were stained with monoclonal antibody ED1 and demonstrated
      phagocytosis of acetylated low-density lipoprotein. The supernatant of the
      macrophages (M phi) suppressed significantly the basal tone of the lymphatic
      bioassay rings precontracted by 10(-8) M U46619. The M phi-induced vasodilation
      of the lymph nodes was significantly reduced by 12 h preincubation of the
      macrophages with 5 x 10(-5) M N omega-nitro-L-arginine methyl ester (L-NAME), 10(
      5) M indomethacin, 10(-6) M dexamethasone, or 10(-5) M cycloheximide.
      Simultaneous preincubation of L-NAME and indomethacin caused a synergistic
      reduction of the M phi-induced vasodilation of the lymphatic bioassay rings. The
      superfusion of Krebs-bicarbonate solution containing 5 x 10(-5) M L-NAME, 5 x 10(
      5) M aspirin, or the culture medium with no macrophages caused no significant
      effect on the M phi-induced vasodilation. These findings suggest that macrophages
      activated by bacterial LPS produce a marked relaxation of lymphatic smooth
      muscles through the co-release of nitric oxide and vasodilative prostaglandins,
      which may result in the facilitation of edema formation in wound tissues.

PMID- 9159649
TI  - Pressure-interval relationship characterizes left ventricular irregular beat
      contractilities and their mean level during atrial fibrillation.
AB  - How left ventricular (LV) contractility relates to irregular RR intervals during
      atrial fibrillation (AF) is still unclear. We investigated the relationship
      between the LV contractility (Emax) of individual beats and their preceding RR
      intervals during AF in isovolumic contractions is excised cross-circulated canine
      hearts, and additionally in ejecting contractions in in situ canine hearts.
      Atrial high-frequency electrical stimulation induced AF. We recorded a LV
      electrocardiogram, volume and pressure, and calculated the Emax of every
      arrhythmic beat. Multiple linear regression analysis between Emax and the six
      preceding RR intervals of all arrhythmic beats during 1 min AF showed the
      preceding RR interval (RR1) and the pre-preceding interval (RR2) to be the
      predominant predictors of Emax. The Emax-RR1/RR2 scattergram was closely fitted
      by a linear regression line. We found Emax at RR1/RR2 = 1 on the regression line
      to be virtually identical with both mean Emax during AF and stable Emax obtained
      during irregular atrial pacing at the same intervals as the mean RR interval
      during AF. These results newly indicate that the pressure-interval relationship
      predominantly characterizes LV irregular beat contractilities and their mean
      level during AF.

PMID- 9159650
TI  - Modulation of inwardly rectifying ATP-regulated K+ channel by phosphorylation
      process in opossum kidney cells.
AB  - The role of phosphorylation in modulating an inwardly rectifying ATP-regulated K+
      channel with inward conductance of about 90 pS was examined using the patch-clamp
      technique on opossum kidney (OK) cells. The activity of the inwardly rectifying
      K+ channel observed in cell-attached patches rapidly declined (channel "rundown")
      upon excision of the membrane into inside-out patches in a control bath solution
      (3 mM Mg2+, ATP-free). The declined channel activity was partially restored by
      applying ATP to the bath, and the ATP-induced channel restoration reached the
      near maximal level at an ATP concentration of 3 mM. The channel activity
      maintained by 3 mM ATP in inside-out patches was inhibited by K-252a (10 microM),
      a nonspecific protein kinase inhibitor, or KT5720 (200 nm), a specific inhibitor
      of cyclic AMP (cAMP)-dependent protein kinase (PKA), and was further stimulated
      by the addition of a catalytic subunit of PKA (20 nM). In cell-attached patches,
      the channel activity was also inhibited by K-252a (10 microM) or KT5720 (200 nM).
      The application of dibutyryl-cAMP (100 microM) alone failed to enhance channel
      activity, but significantly stimulated channel activity after the pretreatment of
      cells with Ro-20-1724 (100 microM), an inhibitor of cAMP-specific
      phosphodiesterase. These results suggest that maintenance of the activity of ATP
      regulated K+ channels in OK cells requires protein kinase-mediated
      phosphorylation with ATP-hydrolysis, and that phosphorylation is mainly induced
      by PKA.

PMID- 9159651
TI  - Inhibitory effects of acupuncture manipulation and focal electrical stimulation
      of the nucleus submedius on a viscerosomatic reflex in anesthetized rats.
AB  - To examine the participation of nucleus submedius (Sm) in the medial thalamus of
      pain inhibitory systems, we investigated the effects of acupuncture and focal
      electrical stimulation of the Sm and adjacent brain sites (0.3 ms, 50 Hz, 50-100
      microA, 10 s) on the EMG activity of the external oblique muscle evoked by
      colorectal distension in urethane-anesthetized Wistar rats. The viscerosomatic
      reflex (VSR) activity was suppressed after the administration of morphine (1.0
      mg/kg, i.v.) and the effect was reversed by naloxone (0.5 mg/kg, i.v.).
      Transection of the spinal cord at the Th2 level also eliminated the VSR.
      Acupuncture manipulation applied to the cheek (manual rotation at 1 Hz)
      suppressed the VSR, and this inhibition was eliminated by microinjections of
      lidocaine into the bilateral Sm nuclei (0.5 microliter of 1.0% solution).
      Electrical stimulation in the ventral part but not the dorsal part of the Sm
      suppressed the VSR. The inhibition of the VSR induced by electrical stimulation
      of the Sm was not reversed by the administration of naloxone (1.0 mg/kg, i.v.).
      Electrical stimulation of the adjacent medial thalamic nuclei (mediodorsal
      nucleus (MD) or centromedial nucleus (CM)) and ventrobasal complex (VB) of the
      thalamus had very little effect on the VSR. These results suggests that the Sm is
      not only involved in the relay of nociceptive information to the cortex, but may
      also be involved in a non-opioid mediated pain inhibitory system and may
      participate, at least in part, in the suppressive effects of intense acupuncture
      manipulation on VSR activity.

PMID- 9159652
TI  - Hyposmolality-induced enhancement of ADH action on amiloride-sensitive Isc in
      renal epithelial A6 cells.
AB  - To assess the action of antidiuretic hormone (ADH) and the osmolality of bathing
      solution on amiloride-sensitive Na+ transport, we measured the amiloride
      sensitive short-circuit current (Isc) and single-channel currents in renal
      epithelial A6 cells. The A6 cells were cultured on permeable supports for 9-13 d
      without aldosterone treatment. The basal amiloride-sensitive Isc and the density
      of the amiloride-sensitive Na+ channel at the apical membrane increased as the
      osmolality of the bathing solution decreased. ADH stimulated the amiloride
      sensitive Isc. The stimulatory action of ADH was enhanced by low osmolality. The
      stimulatory action of hyposmolality on the amiloride-sensitive Isc was
      significantly diminished by pretreatment with brefeldin A (BFA, a blocker of
      protein translocation), while BFA had no significant effect on the ratio of ADH
      stimulated amiloride-sensitive Isc to basal amiloride-sensitive Isc. These
      results suggest that hyposmolality stimulates the translocation of amiloride
      sensitive Na+ channels to the apical membrane from the cytosolic store sites of
      the channel, and that ADH may activate amiloride-sensitive Na+ channels pre
      existing in the apical membrane or translocate the channel via BFA-insensitive
      pathways in a manner dependent on the osmolality of the bathing solution in
      aldosterone-untreated A6 cells, differently from aldosterone-treated A6 cells in
      which ADH stimulates the translocation of amiloride-sensitive Na+ channels via
      BFA-sensitive pathways.

PMID- 9159653
TI  - Effect of voluntary exercise on maximal oxygen uptake in young female Fischer 344
      rats.
AB  - The effect of voluntary exercise on maximal oxygen uptake (VO2 max) was studied
      in young female Fischer 344 rats. After 10 weeks of wheel-running training, the
      absolute VO2 max and VO2 max relative to body mass increased without a decline in
      body mass. The running speed eliciting VO2 max, heart and soleus muscle mass, and
      succinate dehydrogenase (SDH) activity in the soleus muscle also increased. These
      results suggest that voluntary exercise is an effective means of increasing the
      aerobic exercise capacity of young female Fischer 344 rats.

PMID- 9159654
TI  - Relationship between Mn-induced contractile inhibition and cyclic AMP content in
      the longitudinal muscle of estrogen-treated rat uterus.
AB  - In longitudinal myometrial strips of estrogen-treated rats, nifedipine (0.03
      microM) induced the gradual inhibition of phasic contractions evoked by
      repetitive electrical stimulations, with inhibition reaching a plateau level
      (43.4 +/- 2.6% of the control group, n = 6) within 20 min. In contrast, 0.5 mM
      induced a rapid and transient suppression of the phasic contractions (58.3 +/-
      8.9% of the control group, n = 10, at 4 min) followed by sustained inhibition of
      the contractions, the level of which was slightly lower than that of the control
      group (84.2 +/- 5.0%, n = 10, at 20 min). The Mn also induced a rapid and
      transient increase in cellular cAMP level, which reached a peak (201.2 +/- 20.8%
      of the control group, n = 5) at 2 min and decreased to the prestimulation level (
      = 100%) within 15 min. Pretreatment with 1 nM isobutylmethylxanthine (IBMX), a
      phosphodiesterase inhibitor, potentiated the effect of Mn on the cAMP level. The
      transient effects of Mn, but not of nifedipine, on the contractions and cAMP
      levels (and their potentiation by IBMX) do not support the simple action of Mn as
      a Ca antagonist, but are compatible with the intracellular dual action of Mn on
      adenylate cyclase.

PMID- 9159655
TI  - Correlates of abnormal urinary albumin excretion rates among primary care
      patients with essential hypertension.
AB  - BACKGROUND: The excretion of small amounts of urinary protein, known as
      microalbuminuria, among patients with essential hypertension is associated with
      increased mortality from cardiovascular disease and, possibly, future renal
      decline. Correlates of microalbuminuria among primary care patients with
      essential hypertension, however, have not been well described. METHODS: One
      hundred forty patients enrolled in a large family practice ambulatory care center
      who had essential hypertension but not diabetes participated in a screening
      project to document cardiovascular and renal diseases in this population.
      Patients underwent a brief physical examination and submitted blood and urine
      samples for analysis. RESULTS: Twenty-five percent of patients had elevated
      urinary albumin excretion (UAE) rates, defined as greater than 30 micrograms/min.
      Patients with elevated UAE rates did not differ from patients without elevated
      UAE rates by age, race, sex, duration of hypertension, or type of
      antihypertensive medications used (if any). Although no patients had abnormally
      elevated glycosylated hemoglobin, after controlling for age and duration of
      hypertension, elevated UAE rates were significantly related to higher mean
      glycosylated hemoglobin levels (odds ratio [OR] = 3.06, 95 percent confidence
      interval [CI] = 1.11 to 8.41) and to current smoking (OR = 3.14, 95 percent CI =
      1.09 to 9.04). CONCLUSIONS: These data are the first in a primary care population
      to show a threefold increase in risk for elevated UAE rates among patients with
      essential hypertension who currently smoke or who have above-average glycosylated
      hemoglobin levels. Although cross-sectional in nature, these data can also point
      toward subgroups of hypertensive patients who have a worse cardiovascular
      prognosis.

PMID- 9159656
TI  - Lack of association between hypertension and hypothyroidism in postmenopausal
      women seen in a primary care setting.
AB  - BACKGROUND: Several studies undertaken in hospital-based specialty clinics have
      reported an association between hypertension and hypothyroidism. This work
      examines the association between these two common disorders in postmenopausal
      women seen within a primary care office setting. METHODS: Seven hundred seven
      postmenopausal women aged 50 years and older were studied using a cross-sectional
      design. Data on thyroid status, hypertension and risk factors, and patient
      demographics were collected from the office medical record. RESULTS: Overall,
      45.4 percent of the population studied had hypertension and 10.9 percent had
      hypothyroidism. Compared with normotensive women, hypertensive women were
      significantly older (66.4 years versus 63.0 years, P < 0.0001) and had a higher
      body mass index (29.2 kg/m2 versus 26.2 kg/m2, P < 0.0001). Hypertension was
      significantly associated with diabetes mellitus and the use of NSAIDS (odds
      ratios [ORs] = 1.77 and 2.63, respectively). We did not find a significant
      association between hypertension and hypothyroidism (OR 1.04, 95 percent
      confidence interval 0.64 to 1.76 CONCLUSIONS: In this population of
      postmenopausal women we did not find hypertension to be associated with
      hypothyroidism.

PMID- 9159657
TI  - Health assessment for partners of pregnant women: a pilot study of four survey
      methods.
AB  - BACKGROUND: Health assessment for partners of pregnant women has not been
      routinely offered. Work in the area of smoking cessation suggests that a
      partner's health habits have a strong influence on the health habits of a
      pregnant woman. Smoking, alcohol abuse, depression, battering, and household
      firearms cab adversely affect the health of the expectant mother and the infant.
      METHODS: Four methods of partner assessment were pilot tested: office visit with
      a family physician, office visit with a registered nurse, telephone survey
      conducted by the registered nurse, and mailed questionnaire. Written feedback and
      referrals were provided to all study participants, and verbal feedback and
      referrals were provided to those who completed in-person or telephone interviews.
      A chart review was conducted to determine participation bias. RESULTS: Thirty
      five pregnant women and 25 partners participated in the study. Self-administered
      questionnaires and telephone interviews were preferred by study participants. The
      study group was healthier than the general population. Five partners reported
      troublesome drinking behavior, and 1 reported smoking two packs of cigarettes per
      day. CONCLUSIONS: health assessment of partners of pregnant women seems promising
      for uncovering health problems that would be likely to have an adverse impact on
      the health of the family. Further development of assessment and intervention
      strategies is needed.

PMID- 9159659
TI  - Using a clinical practice guideline to measure physician practice: translating a
      guideline for the management of heart failure.
AB  - BACKGROUND: Effective clinical practice guidelines should improve clinical
      outcomes, and measures of physician use of clinical practice guidelines should
      correlate with improved outcomes. This study translates a clinical practice
      guideline on heart failure into review criteria to measure physician performance
      and the effectiveness of the clinical practice guideline. METHODS: A panel of 11
      family physicians and 1 cardiologist systematically reviewed the clinical
      practice guideline for its clinical importance, educational relevance, and
      evaluative appropriateness. Then a subset of 4 family physicians rigorously
      applied each recommendation to established criteria for measurability and
      developed an evaluation tool useful in medical record review. RESULTS: The heart
      failure clinical practice guideline was found to be an excellent educational
      tool. Using it to measure physician performance, however, was limited to
      diagnostic tests and drug prescribing. Of 45 recommendations, 5 fulfilled
      criteria for measurability; 1 recommendation had A-level evidence, whereas 2
      recommendations had B-level and 2 had C-level evidence. CONCLUSION: This study
      illustrates the logistic issues and challenges in developing a measure of
      physician adherence to clinical practice guidelines. Medical record review is
      inadequate to measure many recommendations. Physicians use of this clinical
      practice guideline must be evaluated as an intermediate step to measuring the
      effectiveness of clinical practice guidelines based on patient outcomes.

PMID- 9159658
TI  - Adults with severe reading and learning difficulties: a challenge for the family
      physician.
AB  - BACKGROUND: An estimated 40 to 44 million adults living in the United States have
      severe difficulty reading, writing, spelling, and doing arithmetic. These
      deficiencies interfere with their receiving adequate health care. Many of these
      adults have reading or other learning disabilities that further compromise their
      ability to understand their medical conditions and to participate fully in their
      own care. METHODS: The literature on the cognitive and effective characteristics
      of adults with reading and learning disabilities was searched using the MEDLINE,
      PsychLIT, and ERIC databases. This literature is reviewed with an emphasis placed
      on how these characteristics might challenge a family physician's ability to
      provide optimal patient care, and what can be done to meet these challenges.
      Illustrative case vignettes of adults with these disabilities are described.
      RESULTS AND CONCLUSIONS: The cognitive and affective characteristics of this
      patient population make it difficult for the family physician to provide optimal
      medical services. Suggestions are given to make medical care more accessible and
      appropriate for these patients.

PMID- 9159660
TI  - Treatment of non-insulin-dependent diabetes mellitus with metformin.
AB  - BACKGROUND: Metformin alleviates hyperglycemia of non-insulin-dependent diabetes
      mellitus (NIDDM) by inhibiting hepatic glucose production and improving
      peripheral insulin sensitivity. In contrast to sulfonylureas, metformin does not
      stimulate insulin-secretion, promote weight gain, exacerbate hyperinsulinemia, or
      cause hypoglycemia. It also favorably affects serum lipids. METHODS: A
      comprehensive review of the medical literature from 1968 to the present was
      conducted using the key words "metformin" and "non-insulin-dependent diabetes
      mellitus." RESULTS: Metformin monotherapy was superior to placebo and comparable
      to sulfonylureas in reducing fasting plasma glucose and glycosylated hemoglobin
      levels in patients with NIDDM uncontrolled by diet. Metformin and sulfonylureas,
      however, had diverse effects on body weight and fasting plasma insulin levels;
      both weight and insulin levels remained unchanged or decreased with metformin and
      increased with sulfonylureas. In patients with secondary sulfonylurea failure,
      the combination of metformin and a sulfonylurea synergistically improved glycemic
      control better than either drug alone and was comparable to insulin plus
      sulfonylurea. When hyperglycemia is uncontrolled by insulin after secondary
      sulfonylurea failure, limited data suggest the efficacy of metformin plus
      insulin. The mild, transient, self-limited gastrointestinal side effects that
      sometimes occur can be minimized by gradually increasing the doses and by taking
      metformin with food. Risk of metformin-associated lactic acidosis is low if
      prescribing guidelines are adhered to. Potential adverse drug interactions
      include hypoglycemia during concurrent sulfonylurea therapy and elevated
      metformin plasma concentrations when metformin is taken concomitantly with
      cimetidine. CONCLUSIONS: Metformin can be used safely and effectively as first
      line monotherapy in NIDDM or in combination with a sulfonylurea when monotherapy
      with either agent fails. It can be particularly suitable when weight gain,
      hyperlipidemia, and hypoglycemia are clinically important issues.

PMID- 9159663
TI  - Hand-washing frequency and factors that influence it in a family practice clinic.

PMID- 9159662
TI  - Amaurosis and pulselessness in a young white woman: a case of Takayasu disease.

PMID- 9159664
TI  - Cultural encounters and family medicine: six lessons from South America.

PMID- 9159661
TI  - Medical necessity: making sense out of nonsense.

PMID- 9159665
TI  - Challenges in measuring adherence to clinical practice guidelines.

PMID- 9159666
TI  - Value of review of systems.

PMID- 9159667
TI  - Pneumococcal vaccination.

PMID- 9159668
TI  - Breath test, endoscopy, and peptic ulcer disease.

PMID- 9159669
TI  - Corneal shape changes and astigmatic aspects of scleral and corneal tunnel
      incisions.

PMID- 9159670
TI  - The challenge of self-restraint: our responsibility as refractive surgeons.

PMID- 9159671
TI  - At the forefront of the IOL revolution. Cornelius D. Binkhorst, MD.

PMID- 9159672
TI  - Consultation section. Cataract and refractive surgical problems.

PMID- 9159674
TI  - Enlarging the capsulorhexis.
AB  - We describe a method to enlarge an initial small capsulorhexis using an iris
      spatula and cystotome needle. The iris spatula is placed underneath the anterior
      capsulorhexis margin; the spatula supports the anterior capsule and protects the
      posterior capsule. A gentle touch on the spatula by the cystotome needle
      generates a break in the continuity. This is done prior to intraocular lens
      implantation with the capsular bag and anterior chamber filled with viscoelastic.

PMID- 9159673
TI  - Supracapsular phacoemulsification: a capsule-free posterior chamber approach.
AB  - We describe a technique that relocates the phacoemulsification process outside
      the capsular bag by transposing the nucleus through an intact 5.0 to 6.0 mm
      capsulorhexis. The upside-down nucleus is then returned to the posterior chamber,
      positioned above the anterior capsule in the "supracapsular space" where it
      remains throughout the phacoemulsification procedure of choice: cracking,
      chopping, manual prechoping, or traditional sculpting. The chief advantage of
      supracapsular phacoemulsification is greater efficiency, which is manifested in
      reduced emulsification time and energy. Disadvantages include the possibility of
      mild postoperative corneal edema during the earliest part of the learning curve,
      as well as inadvertent damage to the iris in cases with suboptimal pupil
      dilation.

PMID- 9159675
TI  - Postoperative astigmatism and relative strength of tunnel incisions: a
      prospective clinical trial.
AB  - PURPOSE: To investigate the influence of incision depth and site on wound
      strength and postoperative astigmatism. SETTING: Virchow Memorial Hospital Eye
      Clinic, Berlin, Germany. METHODS: In this prospective, randomized study, 180
      patients with a 7.0 mm tunnel incision depth of 300 and 500 microns; limbal
      incision and scleral incision; temporal scleral incision and scleral incision at
      the 12 o'clock position; temporal limbal incision and limbal incision at the 12
      o'clock position. Postoperative astigmatism was measured by keratometry and
      videokeratoscopy 1 day, 1 and 4 weeks, and 8 months postoperatively. Wound
      strength was measured with an ophthalmodynamometer on the first postoperative day
      and after 1 week at the site with the least mechanical stability adjacent and
      posterior to the primary incision. RESULTS: The temporal incision, which was
      performed 1.0 mm behind the surgical limbus, led to induced astigmatism of 0.65
      diopters (D) +/- 0.23 (SD) after 8 months. When incision was at the 12 o'clock
      position, the induced astigmatism was 0.97 +/- 0.41 D. Induced astigmatism was
      highest following a limbal incision in the 12 o'clock position (1.33 +/- 0.63 D).
      This effect was less pronounced with a temporal incision. Incision depth did not
      significantly influence induced astigmatism. An incision depth of 500 microns led
      to induced astigmatism of 0.94 +/- 0.50 D; a depth of 300 microns led to induced
      astigmatism of 0.78 +/- 0.64 D. After 1 week, wound strength was highest with
      temporal scleral incisions (38.6 +/- 2.1 kPa by ophthalmodynamometer) and lowest
      with limbal incisions in the 12 o'clock position (30.8 +/- 7.7 kPa). CONCLUSIONS:
      Incisions site significantly influenced mechanical wound strength and induced
      astigmatism; incision depth influenced neither. In general, incisions in the 12
      o'clock position induced more astigmatism than temporal incisions.

PMID- 9159676
TI  - Corneal versus scleral tunnel incision in cataract surgery: a randomized study.
AB  - PURPOSE: To compare the induced regular and irregular astigmatism after scleral
      and corneal tunnel incision. SETTING: University hospital outpatient cataract
      clinic. METHODS: One hundred phacoemulsification patients with less than 1.0
      diopter (D) of preoperative astigmatism were randomly assigned to have a clear
      corneal incision (50 patients) or a scleral tunnel incision (50 patients). All
      incisions were 3.5 to 4.0 mm wide and were made in the steepest axis of the
      corneal astigmatism. The surgically induced astigmatism was analyzed by vector
      analysis from keratometric data, as well as by Fourier harmonic series analysis
      of the topographic data. RESULTS: One day after surgery, the surgically induced
      astigmatism (vector analysis, keratometry) was 1.41 D +/- 0.66 (SD) and 0.55 +/-
      0.31 D in the corneal incision group and the scleral incision group, respectively
      (P < .01). Six months after surgery, the induced astigmatism was 0.72 +/- 0.35 D
      and 0.36 +/- 0.21 D in the two groups, respectively (P < .01) The corneal
      topography data confirmed the regular astigmatism changes found by conventional
      keratometry. However, in addition, Fourier harmonic series analysis of the
      topography data showed significantly more irregular induced astigmatism with the
      corneal approach than with the scleral approach. CONCLUSION: The clear corneal
      incision induces significantly more regular as well as irregular astigmatism than
      the scleral tunnel incision.

PMID- 9159677
TI  - Corneal changes after cataract surgery with 5.0 mm sutured and 3.5 mm sutureless
      clear corneal incisions.
AB  - PURPOSE: To study corneal changes after endocapsular phacoemulsification cataract
      extraction and intraocular lens (IOL) implantation with a 3.5 mm clear corneal
      sutureless incision or a 5.0 mm clear corneal incision with an absorbable suture.
      SETTING: Northwest Kansas Eye Clinic, Hays, Kansas, USA. METHODS: In a
      prospective study, 200 eyes were randomly distributed into two groups. Group A
      comprised 100 eyes that had a silicone IOL inserted through a 3.5 mm sutureless
      clear corneal incision. Group B comprised 100 eyes that had a 5.0 mm poly(methyl
      methacrylate) (PMMA) IOL inserted through a 5.0 mm clear corneal incision; one
      half of the closures used a single radial suture (Group B1), and the other half,
      an X suture (Group B2). Preoperatively, corneal topography and corneal
      endothelial cell counts were performed. Six to 8 months postoperatively, they
      were repeated and evaluated. Differential topography was used to determine the
      difference between the preoperative and postoperative corneas. During the final
      postoperative visit, IOL centration was evaluated. RESULTS: All closures produced
      only minimal changes in the corneal topographic indices. The postoperative
      corneas closely resembled the preoperative corneas. Polar K values showed a
      slight astigmatic shift in all groups. Group B2 was the only one to exhibit a
      with-the-rule shift. The change in endothelial cell counts was minimal and
      comparable in all three groups. CONCLUSION: The small amount of change in the
      corneal indices, especially in surface regularity, indicates that all corneas
      were relatively comparable and stable 6 to 9 months postoperatively regardless of
      the type of incision and closure method.

PMID- 9159678
TI  - Comparative study of intraocular lens implantation through 3.0 mm temporal clear
      corneal and superior scleral tunnel self-sealing incisions.
AB  - PURPOSE: To compare the clinical outcome of phacoemulsification and foldable
      silicone intraocular lens (IOL) implantation through a 3.0 mm temporal clear
      corneal incision and 3.0 mm superior scleral tunnel incision. SETTING: Department
      of Ophthalmology, Yodogawa Christian Hospital, Osaka, Japan. METHODS: Eighty
      cataractous eyes of 78 patients with pre-existing against-the-rule (ATR)
      astigmatism were recruited for this prospective, randomized study. The patients
      were assigned to one of the two groups. Data on uncorrected and corrected visual
      acuities, keratometry, flare intensity measurement, and central cornea
      endothelial cell count were evaluated preoperatively and at 2 days, 1 week, and 1
      and 3 months postoperatively. RESULTS: Although the pre-existing keratometric
      cylinder decreased in the temporal clear corneal incision group and increased in
      the superior scleral tunnel incision group, the amount of cylinder shift was not
      significantly different. Mean scalar shift of keratometric cylinder in the
      corneal incision group was 1.19 diopters (D) at 2 days postoperatively, 0.86 D at
      1 week, and 0.56 D at 3 months and in the scleral incision group, 1.09 D at 2
      days, 0.76 D at 1 week, and 0.65 D at 3 months. Eighty percent of the eyes in
      each group achieved an uncorrected visual acuity of 20/40 or better from the
      second day postoperatively. No statistically significant difference in visual
      rehabilitation or other parameters was noted between the groups throughout the
      study. Complications including corneal endothelial cell loss and wound
      incompetence requiring suturing were observed in the temporal clear corneal
      incision group. CONCLUSIONS: Both incisions offered satisfactory clinical
      results, but the superior scleral tunnel incision resulted in fewer
      complications. Minimal corneal keratometric change induced by a 3.0 mm incision
      was not related to uncorrected visual rehabilitation.

PMID- 9159679
TI  - Long-term astigmatic changes after clear corneal cataract surgery.
AB  - PURPOSE: To assess long-term astigmatic changes after clear corneal cataract
      surgery. SETTING: Stadtisches Klinikum, Augenklinik, Karlsruhe, Germany. METHODS:
      We evaluated the first 100 of 2,800 patients having cataract surgery with a
      superior or lateral corneal self-assessing incision and implantation of a 5.0 mm
      poly(methyl methacrylate) intraocular lens. Surgically induced astigmatism (IA)
      and absolute astigmatism (AA) were evaluated after 1 week and 1 and 2 years using
      keratometry and corneal topography. Statistical analysis was done using the
      Wilcoxon signed-rank test. RESULTS: In eyes with a 12 o'clock incision (n = 50),
      the mean IA was 1.18 diopters (D) +/- 0.79 (SD) after 1 year and 1.53 +/- 0.95 D
      after 2 years. In eyes that had with-the-rule astigmatism preoperatively (n =
      15), the mean AA was 0.62 +/- 0.57 D after 1 year and 0.93 +/- 0.56 after 2
      years. In eyes with lateral incisions (n = 50), the mean IA was 0.96 +/- 0.74
      after 1 year and 0.64 +/- 0.50 after 2 years. In eyes with against-the-rule
      astigmatism preoperatively (n = 15), the mean AA was 0.66 +/- 0.70 after 1 year
      and 0.52 +/- 0.65 after 2 years. The between-group difference in astigmatism
      after 2 years was statistically significant. CONCLUSION: The 12 o'clock incision
      was associated with a statistically insignificant increase in AA 2 years
      postoperatively and the lateral incision, with a statistically significant
      decrease. We currently recommend routine use of clear corneal incisions in
      cataract surgery.

PMID- 9159680
TI  - Surgically induced astigmatism following a 4.0 mm sclerocorneal valve incision.
AB  - PURPOSE: To determine whether sutureless small incision cataract surgery reduces
      induced astigmatism over the long term. SETTING: University Eye Hospital, Vienna,
      Austria. METHODS: In a prospective study, we investigated surgically induced
      astigmatism in 63 cases of no-stitch, small incision cataract surgery with a 4.0
      mm square sclerocorneal tunnel and implantation of a flexible intraocular lens.
      Follow-up was 4 to 5 years. Keratometry was measured with a Zeiss keratometer
      preoperatively and after 1 day, 1 week, 1, 3, and 9 months, and a median of 4.4
      years. In 21 nonoperated eyes, we investigated the natural course of astigmatism
      over 5 years. RESULTS: The mean keratometric cylinder stabilized at 0.8 diopter
      (D) after 1 week and slightly decreased to 1.0 D after 4 to 5 years. Cravy's
      vector analysis showed an immediate against-the-rule (ATR) shift of -0.2 D that
      remained relatively stable until 9 months. Between 9 months and 4.4 years
      postoperatively, there was a statistically significant increase in ATR induced
      astigmatism from -0.2 to -0.5 D. The natural course of astigmatism in the
      nonoperated eyes showed an ATR shift of -0.1 D for the same period. CONCLUSION:
      The result show a small, though statistically significant amount of
      postoperatively induced astigmatism 4 to 5 years after no-stitch, small incision
      cataract surgery.

PMID- 9159681
TI  - Effect of incision location on preoperative oblique astigmatism after scleral
      tunnel incision.
AB  - PURPOSE: To evaluate the effect of incision location or clinically relevant
      preoperative oblique astigmatism. SETTING: Department of Ophthalmology, Virchow
      Medical Center, Humboldt-University, Berlin, Germany. METHODS: This prospective
      study included 68 patients who had phacoemulsification and posterior chamber lens
      implantation using a standardized 7.0 mm self-sealing trapezoidal scleral tunnel
      incision. Each patient was randomly assigned to one of three incision locations:
      Group A, conventional superior incision; Group B, temporal incision; Group C,
      oblique incision centered on the steeper meridian (modified BENT incision).
      Astigmatism analysis was performed by manual keratometry and corneal topography.
      RESULTS: A significant mean reduction in astigmatism of 0.58 diopter (D) (P <
      .01) was achieved in only the modified BENT incision group. Postoperatively,
      significant flattening of 0.27 D (P < .01) in the steeper meridian as well as
      steepening of 0.29 D (P < .01) in the flatter meridian occurred. No decrease in
      astigmatism was noted in the superior or temporal incision groups. Five months
      postoperatively, vector analysis showed that surgically induced astigmatism was
      significantly higher in the superior incision group (1.16 D +/- 0.44 [SD]) than
      in the temporal incision group (0.66 +/- 0.32 D) or modified BENT incision group
      (0.82 +/- 0.50 D). Corneal topographic analysis confirmed these results within +/
      0.3 D. CONCLUSIONS: Only the oblique incision centered on the steeper meridian
      (modified BENT incision) effectively and predictably reduced preoperative oblique
      astigmatism. In eyes with clinically relevant oblique astigmatism, we recommend
      using a modified BENT incision.

PMID- 9159682
TI  - Laser in situ keratomileusis to correct high myopia.
AB  - PURPOSE: To evaluate the effectiveness, predictability, and safety of laser in
      situ keratomileusis (LASIK) in 143 eyes with myopia from 8.00 to 20.00 diopters
      (D). SETTING: Alicante Institute of Ophthalmology, University of Alicante School
      of Medicine, Alicante, Spain. METHODS: This prospective study comprised 143 eyes
      (94 patients) that had LASIK with the Chiron Automated Corneal Shaper and the
      VISX 20/20 excimer laser using a multizone profile and a sutureless hinged
      corneal flap technique. RESULTS: Uncorrected visual acuity of 20/40 or better in
      45.0% of eyes 3 months postoperatively and in 46.4% at 6 months. Best corrected
      visual acuity (BCVA) improved by 0.07 at 3 and 6 months and was stable after 3
      months. Mean spherical equivalent was -13.19 diopters (D) +/- 2.89 (SD)
      preoperatively and +0.51 +/- 1.63 D at 3 months and +0.18 +/- 1.66 D at 6 months
      postoperatively. At 3 months, spherical equivalent was within 1.00 D of
      emmetropia in 57.5% of all eyes, 71.0% of eyes with a baseline refraction from 
      8.00 to -11.99 D (n = 59), 44.4% with a baseline refraction from -12.00 to -15.99
      D (n = 54), and 53.0% of eyes with a baseline refraction from -16.00 to -20.00 D
      (n = 30). The respective 6 month percentages were 60.0, 72.4, 46.0, and 50.0%.
      The regression of effect was similar in all groups (approximately 0.50 D) between
      1 and 3 months, although the high myopia group had further regression.
      Significant corneal steepening and an increase in corneal thickness occurred
      between 1 and 3 months. Flap thickness was always less than predicted with both
      the 130 microns plates, and achieved laser ablation was deeper than programmed.
      The relationships between postoperative refraction and preoperative keratometry
      and postoperative refraction and the difference in achieved versus programmed
      ablation were significant. Complications at 6 months included epithelial
      ingrowth, corneal flap melting, decentered ablation, and irregular astigmatism
      with loss of BCVA, although none was vision threatening. CONCLUSION: In this
      study, LASIK was effective and predictable in the correction of high myopia but
      was more accurate for myopia up to 12.00 D. Current surgical algorithms must be
      modified to improve predictability in higher corrections. Longer follow-up is
      necessary to evaluate long-term incidence of vision-threatening complications.

PMID- 9159684
TI  - Corneal transplant for keratoconus: results in early and late disease.
AB  - PURPOSE: To evaluate the results and complications rates associated with corneal
      transplantation for keratoconus and assess the prospects of using penetrating
      keratoplasty at a much earlier stage. SETTING: Buzard Eye Institute, Las Vegas,
      Nevada, USA. METHODS: In this prospective clinical study, 104 eyes of 76 patients
      had corneal transplantation for keratoconus identified by corneal topography,
      keratometry, pachymetry, and/or retinoscopy. Sutures were removed at a mean of 15
      months; mean follow-up was 42 months. All surgeries were performed by one surgeon
      using a torque-antitorque suture method. Eyes were grouped according to severity
      of the disease: early (n = 24); moderate (n = 47); high (n = 33). Preoperative
      keratometry was 40.00 to 49.00, 50.00 to 59.00, and 60.00 to 90.00 diopters (D),
      respectively. The criteria for corneal transplant were a best spectacle-corrected
      visual acuity of 20/40 or worse and keratoconus clearly identified by one of the
      above methods. Secondary procedures included repair of wound dehiscence (33 eyes,
      31%), relaxing incisions (33 eyes, 31%), wedge resections (5 eyes, 5%), and
      automated lamellar keratoplasty (4 eyes, 4%). RESULTS: Mean postoperative
      uncorrected visual acuity at last follow-up was 0.43 +/- 0.3 (20/50), with 46
      eyes (44%) achieving 20/40 or better. Mean best corrected visual acuity (BCVA) at
      last follow-up was 0.83 +/- 0.2 (20/25). Sixty eyes (58%) achieved 20/40 or
      better BCVA at 1 month and 92 eyes (88%), at 3 months. At last follow-up, mean
      average keratometric astigmatism was 3.10 +/- 1.70 D, mean keratometry was 43.30
      +/- 2.20 D, and mean spherical equivalent was -1.70 +/- 3.00 D. Complications
      included 21 graft rejections (20%); 19 were successfully treated with topical and
      oral steroids. No expulsive hemorrhage or endophthalmitis occurred. CONCLUSIONS:
      The risk-benefit for corneal transplantation has been significantly altered by
      improved surgical and postoperative techniques. The improved results, low
      complication rate, and postoperative enhancement management indicate that corneal
      transplantation is a viable option early in the clinical course of keratoconus.

PMID- 9159683
TI  - Effect of surface photorefractive keratectomy and laser in situ keratomileusis on
      the corneal endothelium.
AB  - PURPOSE: To investigate endothelial cell loss in pairs of fresh human autopsy
      globes following high-diopter myopic photorefractive keratectomy (PRK) or laser
      in situ keratomileusis (LASIK). SETTING: Center for Research on Ocular
      Therapeutics and Biodevices and Magill Laser Center for Vision Correction, Storm
      Eye Institute, Charleston, South Carolina, USA. METHODS: In the first part of the
      study, 12 globes had either -10 diopters (D) multizone surface PRK or -10 D
      single-zone LASIK. In the second part, three groups of 5 globes each had -15 D, 
      20 D, or -25 D multizone-blend LASIK procedures. Fellow globes in both groups
      were used as untreated controls. Corneoscleral buttons were excised from all
      globes. Following 7 days in corneal organ culture, the endothelial surface was
      stained with two vital dyes: calcein-AM and ethidium homodimer. Fluorescence
      microscopy was used to obtain endothelial cell counts. RESULTS: The mean dead
      cells per square millimeter (cells/mm2) were 0.94 in the -10 D PRK treated
      corneas compared with 0.91 in the fellow untreated eyes (P = 0.06(. The mean dead
      cells/mm2 in the -10 D single-zone LASIK-treated corneas and in the fellow
      untreated eyes were 0.61 (P = 0.88). The mean dead cells/mm2 in the -15 D, -20 D,
      and -25 D multizone-blend LASIK-treated corneas were 3.08, 2.33, and 5.55,
      respectively, compared with 3.49, 1.92, and 5.01 in the fellow untreated eyes (P
      = 0.276, P = 0.339, and P = 0.427, respectively). Dead cell counts for treated
      and control paired corneas were highly correlated in all treatment groups.
      CONCLUSIONS: No significant endothelial cell loss occurred after -10 D PRK or
      LASIK corrections up to -25 D. Although this study has limitations that prevent
      direct extrapolation to the clinical situation, it does afford a comparable
      clinical correlate for endothelial cell toxicity following a typical excimer
      laser ablations.

PMID- 9159685
TI  - Casebeer System for refractive keratotomy: patient satisfaction.
AB  - PURPOSE: To evaluate patient satisfaction 3 years after radical keratotomy (RK)
      using the Casebeer nomograms. SETTING: The Werblin Center, Princeton, West
      Virginia. METHODS: This study assessed the satisfaction of 96 patients who had
      bilateral distance correction by RK using the Casebeer System. The cases were
      part of the first 241 consecutive refractive keratotomy procedures (N = 128
      patients) performed by one surgeon. Ninety-nine percent of the 96 patients in
      this study completed a questionnaire on satisfaction and visual symptoms 3 years
      postoperatively. A separate control population of 105 consecutive patients about
      to have RK surgery were asked to complete a questionnaire about their
      preoperative symptoms. RESULTS: Ninety-eight percent of patients were very to
      moderately satisfied 3 years after the procedure, 99% said they would have
      surgery again if given the chance, and 96% said they would recommend it to
      others. However, 69% stated they had mild to very severe symptoms 3 years
      postoperatively compared with 28% in the control group. CONCLUSION: Despite an
      extremely high degree of patient satisfaction, about 99%, the 1% dissatisfaction
      rate seen in this study could have be very significant in this young, potentially
      litigious patient population.

PMID- 9159686
TI  - The torque and tilt gamble.
AB  - PURPOSE: To analyze possible suture configurations at the haptics of posterior
      chamber intraocular lenses (IOLs) and estimate the resulting tilt. SETTING: King
      Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia. METHODS: Using a
      plastic cylinder with two pairs of holes drilled on opposite sides and an IOL
      with eyelets in the haptics, we determined possible suture configurations and
      analyzed them for net torque on the IOL haptics that would result in tilting of
      the optic. RESULTS: We identified 64 combinations of regular and countless
      combinations of irregular suture configurations. Among the 16 most likely
      combinations, only 4 were torque-free (or torque neutral), 2 caused maximum tilt,
      and 10 induced some tilting. Theoretically, torque could be eliminated by radial
      suture placement, but this is anatomically undesirable, and by positioning the
      eyelet perpendicular to the haptic, but this is technically difficult. Longer
      suture bites tended to lessen the torsion on the haptic but increased the risk of
      the suture looping around the free end of the haptic. CONCLUSION: Surgeons using
      scleral fixation of a posterior chamber IOL should be aware of the possibility of
      inducing tilt and should aim for symmetrical suture configurations at the two
      haptics.

PMID- 9159687
TI  - Comparison of keratometric values of healthy and diseased eyes measured by Javal
      keratometer, EyeSys, and PAR.
AB  - PURPOSE: To compare the simulated keratometric results of the PAR CTS and the
      EyeSys corneal imaging systems with Javal keratometer readings in keratoconus
      eyes, in eyes after corneal grafting, and in healthy eyes. SETTING: Cornea
      Service, Wills Eye Hospital, Philadelphia, Pennsylvania, USA. METHODS: This
      prospective study evaluated 69 patients divided into three groups (keratoconus; 6
      to 12 months postkeratoplasty; normal corneas) treated at the cornea service. The
      eyes were measured with each of the three instruments. Keratometry results and
      number of attempts needed to obtain the results were collected. RESULTS: Thirty
      keratoconus, 18 transplanted, and 21 normal corneas were examined. The PAR CTS
      Imaged all corneas and the EyeSys, 86% (P = .000627). The PAR CTS and Javal flat
      and steep K-readings in all three groups were the same. The EyeSys simulated
      keratometry results were lower than those of Javal keratometer in the flat K (P <
      .00001) and steep K (P < .00001) in the normal group and in the steep K in the
      transplanted cornea group (P = .00823). The EyeSys also measured less astigmatism
      than the Javal in the normal (P = .00124) and transplanted cornea groups (P =
      .00376). CONCLUSION: The PAR CTS was better able than the EyeSys to provide
      keratometric values that agreed with those obtained with the Javal keratometer.

PMID- 9159688
TI  - Off-axis photorefractive eye screening in children.
AB  - PURPOSE: To determine the utility of mass photoscreening for detecting visual
      anomalies in young, school-age children. SETTING: Seventy elementary schools in
      Alabama, Florida, Georgia, North Carolina, and Virginia, USA. METHODS: An off
      axis photorefractive technique was used to screen 14,591 children in
      kindergarten, first, and fourth grades in 70 schools in 5 southeastern states in
      the United States. RESULTS: A total of 14,075 (96.5%) of the screenings yielded
      analyzable photographs. Overall, 647 (4.6%) children had significant ocular
      findings; significant was defined as hyperopia 2.50 diopters (D) or more, myopia
      1.00 D or more, anisometropia 1.00 D or more, astigmatism 2.00 D or more, media
      opacity 1.0 mm or more in diameter, or 5 degrees or more or 10.00 prism diopters
      or more of ocular misalignment. Another 950 (6.7%) had possibly significant
      findings, defined as the sign being present but in an amount less than that
      considered significant. The most common refractive error was myopia (4.5%),
      followed by anisometropia (3.1%), hyperopia (2.9%), and astigmatism (1.0%).
      Alignment problems were found in 1.7% and media opacities in 0.1%. Among the 1.0%
      with other ocular anomalies were cases of anisocoria greater than 2.0 mm or
      irregular pupils, ptosis greater than 2.0 mm, and subconjunctival hemorrhages. In
      all, 202 children had significant anomalies thought to predispose to amblyopia,
      including 196 with significant anisometropia and 6 with significant lens
      opacities. At a screening cost of $5 per child for the whole study, the cost of
      identifying these children with potentially blinding eye disease was $361 each.
      CONCLUSION: Mass photoscreening may be used to detect amblyogenic conditions in
      children early enough to prevent blindness with timely and appropriate treatment.

PMID- 9159689
TI  - Intraoperative and postoperative complications of high-frequency capsulotomy and
      continuous curvilinear capsulorhexis.
AB  - PURPOSE: To compare the intraoperative complications and postoperative blood
      aqueous barrier (BAB) disturbance after high-frequency capsulotomy and continuous
      curvilinear capsulorhexis (CCC). SETTING: Vienna General Hospital, Vienna,
      Austria. METHODS: This prospective, randomized clinical study evaluated 53 eyes
      with senile cataract. Patients were divided into two groups: high-frequency
      capsulotomy (n = 27) or CCC (n = 26). The surgical procedure and postoperative
      therapy were standardized for both groups. The intraoperative course was
      documented, and postoperative complications were examined by biomicroscopy 3
      months postoperatively. Without the pupil dilated, BAB disturbance was evaluated
      with a laser flare-cell meter at 1, 3, 7, and 14 days postoperatively. The
      findings were analyzed statistically. RESULTS: Intraoperatively, the high
      frequency capsulotomy group had a significantly higher rate of radial tears in
      the anterior lens capsule. Postoperatively, this resulted in a higher incidence
      of postoperative false positioning of the intraocular lens. At no time were the
      flare-cell meter results between groups statistically significant. CONCLUSION:
      High-frequency capsulotomy resulted in no more trauma than CCC. It can be a good
      alternative to conventional techniques, particularly in eyes with no red reflex.
      However, the technique is associated with less mechanical stability.

PMID- 9159690
TI  - Corneal endothelial protection by different viscoelastics during
      phacoemulsification.
AB  - PURPOSE: To evaluate corneal endothelium morphology and function after
      phacoemulsification using different viscoelastics. SETTING: Eye Clinic,
      University of Trieste, Italy. METHODS: This prospective, randomized study
      included results of preoperative and postoperative (7, 30, and 90 days)
      examinations of 66 patients scheduled for phacoemulsification without ocular
      pathology; 8 patients were excluded. Patients were randomly assigned to one of
      four groups based on type of viscoelastic used: 1% sodium hyaluronate (Healon);
      1.4% sodium hyaluronate (Healon GV); 4% sodium chondroitin sulfate-3% sodium
      hyaluronate (Viscoat); 2% hydroxypropyl methylcellulose (Hymecel). Mean cell
      density and cell size variation coefficient were determined by specular
      microscopy; central corneal thickness, by ultrasonic pachymetry; and endothelial
      permeability coefficient and active pump function, by anterior segment
      fluorophotometry. RESULTS: There were no significant differences in postoperative
      mean cell loss among the groups. The cell size variation coefficient was altered
      in all groups 7 days after surgery and was still impaired at 30 days in the
      Hymecel group. A significant increase in mean corneal thickness, endothelial
      permeability, and active pump function occurred in the Healon and Hymecel groups
      7 days after surgery. These parameters were still altered 30 days after surgery
      in the Hymecel group. Endothelial functional alterations did not occur in the
      Healon GV or Viscoat group. CONCLUSION: Viscoat and Healon GV are effective in
      minimizing functional damage of endothelial structure in the early medium-term
      postoperative period.

PMID- 9159691
TI  - Heparin eyedrops to prevent posterior capsule opacification.
AB  - PURPOSE: To evaluate whether heparin eyedrops prevent or reduce posterior capsule
      opacification (PCO) after extracapsular cataract extraction (ECCE) with
      intraocular lens (IOL) implantation. SETTING: Institute of Ophthalmology,
      University G. d'Annunzio, Chieti, Italy. METHODS: This 4 year, prospective, case
      controlled study evaluated 200 patients who had ECCE and implantation of the same
      type of posterior chamber IOL. Patients were randomly assigned to receive topical
      heparin eyedrops postoperatively (heparin group, n = 100) or not to receive the
      eyedrops (control group, n = 100). Postoperative cell response, cellular
      precipitates on the IOL, and presence of PCO were evaluated. RESULTS: There were
      no significant differences between groups in postoperative inflammation. The
      incidence of cellular precipitates was significantly lower in the heparin group
      than in the control group (P < .001). A neodymium:YAG (Nd:YAG) posterior
      capsulotomy was done in 7 patients in the heparin group and 14 in the control
      group (P = .15). During the first 24 months after surgery, the heparin group had
      a significantly lower incidence of Nd:YAG capsulotomy (P < .05) and fibrotic PCO
      (P = .02). CONCLUSION: Topical heparin eyedrops were effective in reducing
      fibrotic PCO in the long term, indicating their usefulness in the postoperative
      management of ECCE.

PMID- 9159692
TI  - Keratitis from corneal anesthetic abuse after photorefractive keratectomy.
AB  - After having photorefractive keratectomy (PRK), a 29-year-old man suffered from
      delayed epithelial healing and corneal stromal ring infiltrates. All laboratory
      results including smear, culture, and biopsy for bacteria, herpes simplex virus,
      and Acanthamoeba were negative. The suspected cause was patient abuse of
      anesthetics. Subsequently, it was discovered that for 6 months, since just after
      the PRK, the patient had intermittently used topical proparacaine drops. After
      all medication was discontinued and the eye pressure patched, the corneal
      epithelium healed completely. Practitioners should consider the possibility of
      topical anesthetic abuse in cases of keratitis after PRK.

PMID- 9159693
TI  - Capsulorhexis-related lacteocrumenasia.
AB  - Three patients who presented with a milky fluid in the space between the
      posterior surface of implanted intraocular lens (IOL) and the anterior surface of
      the distended posterior capsular bag are described. The patients were followed
      and were noted to have changes in their benign course after several years. The
      occurrence of this milky-fluid-filled capsular bag is extremely uncommon and is
      difficult to perceive if the observer is not looking for it.

PMID- 9159694
TI  - Determinants of case selection at morning report.
AB  - OBJECTIVE: To determine why residents present certain cases and not others at
      morning report (MR) in an institution that permits residents the free choice of
      cases. DESIGN/PARTICIPANTS: Prospective survey of 10 second- and third-year
      residents assigned to the medical service. SETTING: A 241-bed teaching hospital
      with 55 categorical internal medicine residents. MEASUREMENTS AND MAIN RESULTS:
      Over a 4-week period, there were 194 admissions to the medical service on 18 call
      days preceding MR. Of these admissions, 30 (15%) were presented at MR. Cases were
      more likely to be presented if they were considered unusual or rare in
      presentation or incidence (P = .001), involved significant management issues (p =
      .001), or were associated with remarkable imaging studies or other visual
      material (p = .006). Residents were more likely to present cases in which they
      disagreed with attending physicians on management plans (p = .005). Overall,
      residents rated few admissions as having notable physical examination findings
      (29/194) or ethical or cost issues (6/194). Of the seven most common admitting
      diagnoses, representing 44% of admissions, residents did not present cases
      involving four of these diagnoses. CONCLUSIONS: Residents presented cases at MR
      that they felt were unique or rare in presentation or incidence for purposes of
      discussing management issues. Complete resident freedom in choosing MR cases may
      narrow the scope of MR and exclude common diagnoses and other issues of import
      such as medical ethics or economics.

PMID- 9159695
TI  - Do patient preferences contribute to racial differences in cardiovascular
      procedure use?
AB  - OBJECTIVE: To determine whether patient preferences for the use of coronary
      revascularization procedures differ between white and black Americans. DESIGN:
      Cross-sectional survey. SETTING: Tertiary care Department of Veterans Affairs
      hospital. PATIENTS: Outpatients with and without known coronary artery disease
      were interviewed while awaiting appointments (n = 272). Inpatients awaiting
      catheterization were approached the day before the scheduled procedure (n = 80).
      Overall, 118 blacks and 234 whites were included in the study. MEASUREMENTS AND
      MAIN RESULTS: Patient responses to questions regarding (1) willingness to undergo
      angioplasty or coronary artery bypass surgery if recommended by their physician
      and (2) whether they would elect bypass surgery if they were in either of two
      hypothetical scenarios, one in which bypass surgery would improve symptoms but
      not survival and one in which it would improve both symptoms and survival. Blacks
      were less likely to say they would undergo revascularization procedures than
      whites. However, questions dealing with familiarity with the procedure were much
      stronger predictors of a positive attitude toward the procedure use. Patients who
      were not working or over 65 years of age were also less interested in procedure
      use. In multivariable analysis race was not a significant predictor of attitudes
      toward revascularization except for angioplasty recommended by their physician.
      CONCLUSIONS: Racial differences in revascularization rates may be due in part to
      differences in patient preferences. However, preferences were more closely
      related to questions assessing various aspects of familiarity with the procedure.
      Patients of all races may benefit from improved communication regarding proposed
      revascularization. Further research should address this issue in patients
      contemplating actual revascularization.

PMID- 9159696
TI  - Meta-analysis of randomized control trials addressing brief interventions in
      heavy alcohol drinkers.
AB  - OBJECTIVE: To assess the effectiveness of brief interventions in heavy drinkers
      by analyzing the outcome data and methodologic quality. DESIGN: (1) Qualitative
      analysis of randomized control trials (RCTs) using criteria from Chalmers'
      scoring system; (2) calculating and combining odds ratios (ORs) of RCTs using the
      One-Step (Peto) and the Mantel-Haenszel methods. STUDY SELECTION AND ANALYSIS: A
      MEDLINE and PsycLIT search identified RCTs testing brief interventions in heavy
      alcohol drinkers. Brief interventions were less than 1 hour and incorporated
      simple motivational counseling techniques much like outpatient smoking cessation
      programs. By a single-reviewer, nonblinded format, eligible studies were selected
      for adult subjects, sample sizes greater than 30, a randomized control design,
      and incorporation of brief alcohol interventions. Methodologic quality was
      assessed using an established scoring system developed by Chalmers and
      colleagues. Outcome data were combined by the One-Step (Peto) method; confidence
      limits and chi 2 test for heterogeneity were calculated. RESULTS: Twelve RCTs met
      all inclusion criteria, with an average quality score of 0.49 + or - 0.17. This
      was comparable to published average scores in other areas of research (0.42 + or 
      0.16). Outcome data from RCTs were pooled, and a combined OR was close to 2
      (1.91; 95% confidence interval 1.61-2.27) in favor of brief alcohol interventions
      over no intervention. This was consistent across gender, intensity of
      intervention, type of clinical setting, and higher-quality clinical trials.
      CONCLUSIONS: Heavy drinkers who received a brief intervention were twice as
      likely to moderate their drinking 6 to 12 months after an intervention when
      compared with heavy drinkers who received no intervention. Brief intervention is
      a low-cost, effective preventive measure for heavy drinkers in outpatient
      settings.

PMID- 9159697
TI  - Symptoms of major depression and tricyclic side effects in primary care patients.
AB  - OBJECTIVE: To examine the prevalence and course of symptoms resembling side
      effects of tricyclic antidepressants among primary care patients experiencing
      major depression and receiving nortriptyline pharmacotherapy. DESIGN: Prospective
      cohort study. PATIENTS: Seventy-five patients meeting DSM-III-R criteria for a
      current major depression. SETTING: Four Pittsburgh (Pa.) ambulatory health
      centers affiliated with residency programs. MEASUREMENTS AND MAIN RESULTS:
      Symptoms resembling tricyclic side effects were assessed at baseline and at
      monthly intervals using the Somatic Symptoms Checklist. The Hamilton Rating Scale
      for Depression and Diagnostic Interview Schedule were used to assess depressive
      severity and history of generalized anxiety or panic disorder, respectively.
      Symptoms resembling tricyclic side effects, including thirst (54%), palpitations
      (51%), and dry mouth (48%), were commonly experienced before commencing
      pharmacotherapy. Patients with severe depressive episodes and those with a
      history of an anxiety or panic disorder had significantly more physical symptoms
      than those with milder episodes of depression and were more likely to drop out of
      care (n = 25) before completing the acute phase of pharmacotherapy. Patients who
      completed the acute phase of pharmacotherapy and those who entered its
      continuation phase (n = 43) experienced significant reduction in many depressive
      and physical symptoms (p < .001). CONCLUSIONS: Symptoms resembling tricyclic side
      effects are common among depressed primary care patients before beginning
      pharmacotherapy and generally remit with the depressive episode. Better awareness
      of major depression's somatic effects and the consequences of therapy could
      result in better management of both physicians' and patients' expectations
      regarding antidepressant pharmacotherapy.

PMID- 9159698
TI  - Hepatitis B among the Khmer. Issues of translation and concepts of illness.
AB  - OBJECTIVE: To assess the comprehensibility of hepatitis B translations for
      Cambodian refugees, to identify Cambodian illnesses that include the symptoms of
      hepatitis, and to combine these observations with critical theoretical
      perspectives of language to reflect on the challenges of medical translations
      generally. DESIGN: Open-ended, semistructured interviews, and participant
      observation of a refugee community in Seattle, Washington. SETTING: Homes of
      Cambodian residents of inner-city neighborhoods. PARTICIPANTS: Thirty-four adult
      Cambodian refugees who had each been educated about hepatitis B through public
      health outreach. RESULTS: Medical interpreters translated hepatitis B as rauk
      tlaam, literally "liver disease." Unfortunately, while everyone knew of the liver
      (tlaam), rauk tlaam was a meaningless term to 28 (82%) of 34 respondents and
      conveyed none of the chronicity and communicability intended by refugee health
      workers for 34 (100%) of the respondents. In contrast, all respondents knew
      illnesses named after symptom complexes that include the symptoms of acute and
      chronic hepatitis, but do not refer to diseased organs. The Cambodian words
      chosen to translate hepatitis B reflect the medical thinking and medical
      authority that can unintentionally overwhelm attempts at meaningful communication
      with non-English-speaking patients. CONCLUSIONS: To improve comprehension of
      hepatitis B translations for the Khmer, translators must choose between medical
      terminology focused on the liver and Khmer terminology which identifies
      recognizable experiences, but represents important Khmer health concepts. A
      critical linguistic view of this situation suggests that for these translations
      to be meaningful clinicians and health educators must first analyze and then
      monitor the contextual significance of medical language. In cross-cultural
      settings, this means a partnership with medical interpreters to pay close
      attention to the experience of illness and social context of the translation.

PMID- 9159699
TI  - A decision analysis for treatment of clinically localized prostate cancer.
AB  - OBJECTIVE: To determine the preferred treatment of clinically localized prostate
      cancer. DESIGN: Cancer grade, patient age, and comorbidities are considered in a
      Markov model with Monte Carlo sensitivity analyses. Large and recent pooled
      analyses and patient-derived utilities are included. RESULTS: Principal findings
      suggest benefit for radical prostatectomy relative to watchful waiting for men
      under 70 years of age with low to moderate comorbidity. Men older than 70 with
      high comorbidity and disease of low to moderate grade do better with watchful
      waiting. CONCLUSIONS: Cohort-level sensitivity analyses suggest a quality-based
      treatment benefit for radical prostatectomy for younger men and treatment harm
      for older men. Tailored patient and clinician decisions remain necessary,
      especially for men older than 70 in good health but with aggressive cancers.

PMID- 9159701
TI  - Attitudes about treatment of coronary heart disease among women and men
      presenting for exercise testing.
AB  - To assess attitudes that could contribute to gender differences in the use of
      coronary procedures, we surveyed 322 patients presenting for exercise testing at
      a major teaching hospital. Adjusting for sociodemographic and clinical factors,
      women and men did not differ significantly in their willingness to seek a second
      opinion, reduce physical activity, or take drugs to avoid major cardiac surgery,
      but men were more likely than women to describe themselves as risk takers on a
      three-item personality measure (adjusted odds ratio 2.5; 95% confidence interval
      1.4-4.6). Patients' attitudes about risk should be explored further in studies of
      gender differences in the use of coronary procedures.

PMID- 9159700
TI  - Intern call structure and patient satisfaction.
AB  - Our institution has instituted "short-call" and "nightfloat" systems to reduce
      the number of admissions to the traditional "long-call" housestaff. However, the
      nightfloat system introduces increased discontinuity to patient care, and interns
      may spend less time with short-call patients because they are nor required to
      spend the night on-call. Discontinuity and less time spent with patients may
      result in decreased patient satisfaction. Over a 6-month period, data were
      collected on 145 consecutive patients admitted to a teaching Veterans Affairs
      Medical Center with the primary diagnoses of congestive heart failure and chronic
      obstructive pulmonary disease. We found that patients admitted to either short
      call or nightfloat interns were significantly less satisfied with their care than
      patients admitted to long-call housestaff, controlling for intern gender, patient
      age, and patient severity of illness (p = 0.02). Residency program directors need
      to realize that changes in the structure of teaching environment may have an
      impact on patient satisfaction.

PMID- 9159702
TI  - Increasing autopsy rates at a public hospital.
AB  - Despite the acknowledged value of autopsies, autopsy rates are low in American
      hospitals. We developed an extensive intervention to increase the autopsy rate on
      the medical service of our urban teaching hospital and to identify obstacles to
      obtaining permission for autopsy. The 6-month intervention increased the autopsy
      rate from 7.5% during the previous 2 years to 16.8%, but this effect disappeared
      after the intervention. Among patients for whom permission for autopsy was nor
      obtained, physicians failed to request permission for 31% and families refused
      permission for 69%.

PMID- 9159703
TI  - The utility of follow-up testing after curative cancer therapy. A critical review
      and economic analysis.
AB  - OBJECTIVE: To review (1) basic principles of follow-up in patients who are in
      complete remission following curative therapy for cancer; (2) evaluate the
      available data on follow-up strategies for testicular cancer, Hodgkin's disease,
      non-Hodgkin's lymphoma, breast cancer, colorectal cancer, small cell and non
      small cell lung cancer, and prostate cancer; and (3) analyze the cost of follow
      up strategies. METHODS: The English language literature was reviewed utilizing
      MEDLINE headings for the specific malignancies and the text word "follow-up."
      Bibliographies of relevant articles also were reviewed. Emphasis was placed on
      prospective, randomized trials of large retrospective studies in which all
      patients who potentially could have been evaluated were accounted. The cost of
      various testing strategies were analyzed utilizing data from the Health Care
      Finance Administration. DATA SYNTHESIS: Proper follow-up strategies should take
      into account patterns and time course of recurrence and should be obtained of
      detection of recurrence would allow meaningful therapeutic intervention. Testing
      also should be directed at early detection of malignant and nonmalignant
      complications known to be associated with the primary disease. Testicular cancer
      is a "model" malignancy in that sensitive tests for recurrence are available and
      early detection of recurrence allows for potentially curative therapy.
      CONCLUSIONS: According to the currently available literature, repetitive follow
      up laboratory and radiologic testing, except for nonseminomatous germ cell
      tumors, does not detect the vast majority of cancer relapses, nor does it result
      in a greater chance of cure or prolonged survival. The majority of recurrences at
      all disease sites will first be recognized as symptomatic changes in the
      patient's condition or alterations in the physical examination. A limited panel
      of blood tests and radiographic studies to detect recurrences, metachronous
      disease, and complications of therapy (malignant and nonmalignant), will suffice
      for most cancers. Though data are limited, this more restrictive policy of follow
      up testing does not appear to adversely impact patient quality of life and result
      in dramatic cost of savings to the health care system.

PMID- 9159704
TI  - The social transformation of medical morning report.

PMID- 9159705
TI  - Physician gender and estrogen replacement therapy.

PMID- 9159706
TI  - Introduction. Health care into the next century.

PMID- 9159707
TI  - The new politics of U.S. health policy.
AB  - Following the demise of comprehensive health care reform in 1994, some reformers
      are seeking comfort in the successful "incremental" strategy for enacting
      Medicare that emerged out of President Harry Truman's failed campaign for
      national health insurance in 1948-50. But despite similarities between the Truman
      and Clinton health security efforts, overall contexts of government and politics
      are much less hospitable to governmentally funded reforms today than they were
      after Truman's defeat. Back then, market transformations and political dynamics
      were both pushing toward expanded access to health services and insurance
      coverage. Today, by contrast, both push in the opposite direction. The private
      insurance market is fragmenting, federal budgetary constraints stymie new
      programs, and the deficit dominates debate over existing programs. Equally
      important, a stable pro-reform coalition like that of Truman's day has yet to
      emerge, while a new and fiercely conservative corps of Republicans is championing
      coherent programmatic alternatives based on antigovernment premises. Although
      passage of the Kassebaum-Kennedy health insurance reform bill in 1996 unleashed a
      wave of enthusiasm about incremental health care reform, formidable political,
      fiscal, and technical obstacles continue to stand in the way of even relatively
      modest incremental solutions.

PMID- 9159708
TI  - The health system in transition: care, cost, and coverage.
AB  - The growth in market-based contracting and the ascendency of managed care have
      generated substantial change in the health care delivery system. These reforms
      were spurred largely by private health care purchasers seeking a means for
      controlling the relentless growth in medical care costs. Following the private
      sector's lead, the two large public programs, Medicaid and Medicare, have also
      looked to managed care for solving their mounting expenditure problems. Increased
      reliance on competition, and the growing rejection of rate regulation, have
      fundamentally re-shaped the health care delivery system and raise several
      important policy issues. Market-based contracting places a premium on the ability
      of health plans to control the growth in prices and use of services, resulting in
      continued merger and consolidation among health plans. At the same time,
      providers have recognized the competitive bargaining advantages in negotiating
      with health plans through their own consolidation and mergers. Unanswered in the
      managed care revolution is the means for financing care for the 41 million
      uninsured Americans. Moreover, whether the private and public sector are willing,
      or need, to finance the training of young physicians also hangs in the balance.

PMID- 9159709
TI  - The dynamics of market-level change.
AB  - Health care exhibits a competitive dynamic today that increasingly resembles that
      in other service industries. Organizations are becoming larger to achieve scale
      economies and to increase market power. Vertical integration, whether through
      ownership or complex contracts, is also being pursued both to seek efficiencies
      and to improve the bargaining position of the organization. External forces that
      are driving these changes include more aggressive activities on the part of
      purchasers to contain their costs, developments in information technology,
      management innovation in other service industries, and advances in medical
      technology. Within the health care industry, there is a pattern of organizations
      taking the initiative to respond to these external forces--often in anticipation
      of them--and other organizations then responding to the pressures in turn placed
      on them. Although information on strategies is communicated rapidly throughout
      the country, what is attempted and what succeeds differs a great deal across
      communities. The nature of current health care institutions in the community,
      including the presence of large entities with extensive capital and strong
      management in a particular segment of the health system and the community's
      experience with managed care are important factors in the path that change takes.

PMID- 9159710
TI  - Can markets give us the health system we want?
AB  - The purpose of this article is to reconsider the foundations of health economics
      as applied to the study of competition. It shows that conclusions concerning the
      purported desirability of competitive markets are based on a number of
      assumptions--many of which have heretofore been ignored--that typically are not
      fulfilled in the health care area. Once this is recognized market mechanisms no
      longer necessarily provide the best way to improve social welfare. The article is
      divided into two parts: competition and demand. Each of these sections presents
      and then critiques key assumptions of the conventional economic model, and then
      provides a number of health applications. It concludes that by not considering
      the validity of these assumptions in health care applications, researchers and
      policy analysts will bind themselves to policy options that may be most effective
      in improving social welfare.

PMID- 9159711
TI  - Going for the gold: the redistributive agenda behind market-based health care
      reform.
AB  - Political conflict over the respective roles of the state and the market in
      health care has a long history. Current interest in market approaches represents
      the resurgence of ideas and arguments that have been promoted with varying
      intensity throughout this century. (In practice, advocates have never wanted a
      truly competitive market, but rather one managed by and for particular private
      interests). Yet international experience over the last forty years has
      demonstrated that greater reliance on the market is associated with inferior
      system performance--inequity, inefficiency, high cost, and public
      dissatisfaction. The United States is the leading example. So why is this issue
      back again? Because market mechanisms yield distributional advantages for
      particular influential groups. (1) A more costly health care system yields higher
      prices and incomes for suppliers--physicians, drug companies, and private
      insurers. (2) Private payment distributes overall system costs according to use
      (or expected use) of services, costing wealthier and healthier people less than
      finance from (income-related) taxation. (3) Wealthy and unhealthy people can
      purchase (real or perceived) better access or quality for themselves, without
      having to support a similar standard for others. Thus there is, and always has
      been, a natural alliance of economic interest between service providers and upper
      income citizens to support shifting health financing from public to private
      sources. Analytic arguments for the potential superiority of hypothetical
      competitive markets are simply one of the rhetorical forms through which this
      permanent conflict of economic interest is expressed in political debate.

PMID- 9159712
TI  - Who was that straw man anyway? A comment on Evans and Rice.

PMID- 9159713
TI  - What does economics have to say about health policy anyway? A comment and
      correction on Evans and Rice.

PMID- 9159714
TI  - The technocratic wish: making sense and finding power in the "managed" medical
      marketplace.
AB  - Enormous changes have recently swept through the organization and delivery of
      medical care. Scholars and students of the health care system and its politics
      try to make sense of the shift in power to identify and allocate needed resources
      away from physicians and toward corporate firms. I suggest that we cannot
      understand managed care unless we understand its power as at least substantially
      due to its reliance on a claim to be better science. In this way, managed care
      needs to be placed within an analytic historical tradition that is concerned with
      how accounts of scientific objectivity become convincing and support (and are
      confirmed as scientific by) social and political objectives. In this way, managed
      care reflects what I call the technocratic wish: an appeal to objective measures
      to resolve contentious issues and/or clothe their resolution as scientifically
      logical and natural.

PMID- 9159715
TI  - The doctor as businessman: the changing politics of a cultural icon.
AB  - From just after the Civil War, when medicine began to professionalize, until the
      late 1970s, doctors and policy makers believed that clinical judgment should not
      be influenced by the financial interests of doctors. Physicians were highly
      entrepreneurial, and organized medicine fought to preserve their entrepreneurial
      interests, but the moral norm that justified their autonomy from state regulation
      was a strict separation of clinical judgment and pecuniary interests. Under
      managed care, the old norm is reversed. A good doctor takes financial
      considerations into account in making clinical decisions. Theoretically, doctors
      should consider measures of cost to society, but in practice, the payment systems
      of managed care plans induce doctors to consider the impact of each clinical
      decision on their own income. Because doctors share the risks of insuring
      patients with managed care plans, they have the same incentives as insurers to
      avoid patients who are expensively sick. The new cultural image of doctors as
      entrepreneurs masks their considerable loss of clinical autonomy under managed
      care. It also serves to persuade doctors to accept managed care arrangements and
      to persuade insurance consumers and patients to accept reduced benefits from
      employers and the government.

PMID- 9159716
TI  - Markets, Medicare, and making do: business strategies after national health care
      reform.
AB  - This essay examines the role of business health care purchasers in keeping market
      solutions at the center of the health system. One might assume that employers
      would have a clear ideological preference for market solutions, but big business
      managers are ambivalent about market interventions at both the firm and public
      policy levels. Although currently enthusiastic about market-oriented managed
      care, large employers have been periodically disappointed by firm-level market
      experiments during the past two decades. They viewed with skepticism the
      Republican proposal to apply private-sector market cures to the public Medicare
      and Medicaid, fearing that the proposals would accelerate cost-shifting to
      private business payers. Big business objections have been muted, however, by the
      organizational weakness so vividly illustrated during the national health reform
      debate.

PMID- 9159717
TI  - Managed care and Medicare reform.
AB  - A primary goal of many Medicare reform proposals is to move program beneficiaries
      into managed care plans operated by private insurance companies. Advocates
      contend that managed care plans, especially health maintenance organizations
      (HMOs), can save substantial money for the federal government, while also
      improving the quality of medical care and scope of covered benefits for Medicare
      enrollees. Should Medicare follow the private sector by adopting managed care
      based reforms? This article summarized the claims that are made for and against
      incorporating managed care into Medicare, and reviews evidence from the program's
      experience with HMOs on financial savings, benefits coverage, and quality of
      care. This evidence raises concerns regarding the ability of HMOs to provide
      adequate care for chronically ill Medicare patients. Moreover, there is
      considerable uncertainty about the future performance of managed care plans. I
      therefore conclude that policy makers should move cautiously in embracing managed
      care and that Medicare should not adopt financial incentives, such as vouchers,
      that are intended to push beneficiaries into HMOs. However, Medicare beneficiary
      enrollment in managed care plans is likely to increase substantially in coming
      years regardless of public policy. It is therefore critical for Medicare to
      pursue policies that protect the quality of care for elderly and disabled
      patients in managed care plans; curtail excessive payments to HMOs that result
      from favorable selection of healthier enrollees; and preserve the current fee-for
      service Medicare program.

PMID- 9159718
TI  - Markets and public programs: insights from Oregon and Tennessee.
AB  - Medicaid is the major national program promoting access to care for low-income
      populations, but the program also is a federal-state partnership. With costs
      rising and universal access still a remote objective, many states have turned to
      market-based strategies involving managed care, with the goals of generating
      savings for the state, improving access for Medicaid beneficiaries, and sometimes
      expanding coverage to those who were previously uninsured. Yet Medicaid is a
      complex social insurance system that over time has been used to finance a variety
      of needs, often using cross-subsidies. In addition, states vary in both the scope
      of their Medicaid programs and the sophistication of the skills and resources
      they can bring to bear in shaping them. Understanding how these influence the
      ability to implement market-based strategies in Medicaid and what the effects of
      these strategies appear to be is of crucial importance because most states now
      include some features of this approach in their programs.

PMID- 9159719
TI  - Clinical and pharmacological differences in early- versus late-onset Parkinson's
      disease.
AB  - We evaluated whether patients with early-onset Parkinson's disease (EOPD) have a
      different clinical profile and pharmacological response than those with late
      onset disease (LOPD). We performed a retrospective analysis and an acute
      pharmacological challenge with L-Dopa in 34 EOPD (age at onset between 21 and 40
      years) and 34 LOPD (onset after age 60) patients. All patients completed a
      structured questionnaire cross-checked against medical record charts and
      underwent an acute levodopa test. Most significant differences were in the mode
      of onset, time of diagnosis, and degree of initial improvement. We did not
      observe differences with regard to motor fluctuations. The acute levodopa test
      showed no differences in latency to response onset between groups. However, the
      magnitude of the response was greater and the duration shorter in EOPD patients.
      Younger patients had greater reductions in bradykinesia scores, whereas
      posture/gait symptomatology was less responsive in older patients. The type and
      severity of dyskinesias also differed significantly between groups. Our findings
      suggest that central pharmacokinetics, pharmacodynamics, and possibly,
      nondopaminergic systems play a role in the age-related differences observed in
      Parkinson's disease.

PMID- 9159720
TI  - Motor fluctuations during continuous levodopa infusions in patients with
      Parkinson's disease.
AB  - The cause of motor fluctuations occurring during constant-rate levodopa infusions
      is unknown. We examined whether known pharmacokinetic factors could explain the
      fluctuations and looked for clues to pharmacodynamic causes. Eleven subjects with
      stage III-V Parkinson's disease (PD) and a fluctuating response to levodopa
      underwent constant-rate infusions for 36-110 h. Levodopa, 3-O-methyldopa (3-OMD),
      and plasma large neutral amino acids (LNAAs) were measured at 2- to 6-h intervals
      and PD was monitored hourly from 07:00 to 22:00 h with tapping speed. Ten
      subjects had motor fluctuations during the infusions. Zero to 68% of the
      variability of tapping speed could be explained by variation in plasma LNAA
      concentrations in individual subjects. Fluctuations occurred more commonly later
      in the day, which may be related to the tendency for LNAAs to increase during the
      day. Motor fluctuations were not associated with minor variations in levodopa or
      3-OMD concentrations. Fluctuations during constant infusions were more marked in
      patients using larger daily doses of oral levodopa; severity of PD did not
      predict fluctuations during the infusions. There was no trend for fluctuations or
      dyskinesia to decrease or increase during several days of constant-rate levodopa
      infusion. A portion of motor fluctuations occurring during constant levodopa
      infusions can be explained by peripheral pharmacokinetic mechanisms. Fluctuations
      are more prominent in subjects who have taken larger daily doses of levodopa,
      implicating pharmacodynamic factors as well.

PMID- 9159721
TI  - A dose-ranging study of selegiline in patients with Parkinson's disease: effect
      of platelet monoamine oxidase activity.
AB  - A dose-ranging study of selegiline was performed in patients with Parkinson's
      disease to determine the minimal dosage of the drug able to inhibit > or = 95% of
      platelet monoamine oxidase (MAO) activity. Different doses of selegiline (5 or 10
      mg daily, 10 or 20 mg weekly) were studied in four groups of six patients with
      Parkinson's disease. Platelet MAO activity was measured before and after 1
      month's treatment with selegiline. The doses of 5 or 10 mg daily and 20 mg (i.e.,
      10 mg x 2) weekly induced a complete inhibition of platelet MAO-B activity from
      day 7 to day 28 (96.0-99.5%). In contrast, platelet MAO-B inhibition was only
      75.9% of the basal value after a dosage of 10 mg weekly. These results
      demonstrate that 20 mg weekly is the minimal dosage of selegiline able to induce
      a maximal and long-lasting inhibition of platelet MAO-B activity in patients with
      parkinsonism. Further clinical trials are needed to investigate the clinical
      efficacy of this dose.

PMID- 9159722
TI  - Unchanged basal ganglia N-acetylaspartate and glutamate in idiopathic Parkinson's
      disease measured by proton magnetic resonance spectroscopy.
AB  - The lentiform nucleus of five patients with idiopathic Parkinson's disease (IPD)
      was studied by quantitative magnetic resonance spectroscopy (MRS), both before
      and after administration of apomorphine, and the spectra were compared with those
      from a group of age-matched normal subjects. The concentrations of the three
      major metabolites, choline, creatine, and N-acetylaspartate (NAA), were
      quantified using tissue water content as an internal concentration reference.
      Glutamate concentration was assessed as the (glutamate + glutamine; GLX)/creatine
      peak area ratio. In normal subjects, the mean +/- SD concentrations of the the
      three metabolites were 2.4 +/- 0.4 mumol/g wet wt for choline, 11.5 +/- 0.8
      mumol/g for creatine, and 14.7 +/- 2.8 mumol/g for NAA. The Glx/creatine ratio
      was 1.26 +/- 0.12. There was no significant difference in these parameters in the
      lentiform nucleus of patients with IPD either before or after apomorphine. The
      absence of detectable differences in IPD in this study implies that the changes
      in glutamate metabolism in the basal ganglia predicted by animal work are more
      subtle than those currently observable by MRS.

PMID- 9159723
TI  - Freezing phenomenon in patients with parkinsonian syndromes.
AB  - Freezing is a common symptom in parkinsonian syndromes, but its association with
      different causes of parkinsonism as well as with other symptoms has never been
      investigated. We conducted a database survey of the occurrence of freezing in
      parkinsonism. Of 347 patients with a clinical diagnosis of parkinsonism other
      than idiopathic Parkinson's disease and with specific data regarding freezing,
      158 patients had freezing (46%). Freezing was significantly associated with
      progression of the disease as rated on the Hoehn & Yahr scale [odds ratio (OR),
      1.69; p < 0.004]. Gender was not a risk factor for the development of freezing.
      Patients with drug-induced parkinsonism were at a very low risk for developing
      freezing (p < 0.00001; OR, 0.1). Freezing was found in a high frequency in
      patients with vascular parkinsonism (57%), normal-pressure hydrocephalus (56%),
      and generally in the group of patients who had parkinsonism resulting from
      neurodegenerative diseases (progressive supranuclear palsy, multiple system
      atrophy, and corticobasal ganglionic degeneration; 45%). Freezing was
      significantly associated with the presence of dementia, incontinence, and
      tachyphemia (OR, 2.01, 1.7, and 5.09, respectively).

PMID- 9159724
TI  - Short-term effects of behavioral treatment on movement initiation and postural
      control in Parkinson's disease: a controlled clinical study.
AB  - In a controlled clinical study, we investigated the effects of behavioral
      treatment on postural and gait initiation problems idiopathic Parkinson's disease
      (PD). Comparable groups of patients received therapy (experimental group, n = 15)
      and nonspecific psychological treatment (control group, n = 14) for 10 weeks. We
      monitored various variables reflecting properties of posture and gait initiation
      by using an optoelectronic motion analyzer (electronic movement analysis system,
      ELITE). A clinician blind to group membership of the patients assessed PD
      severity with the United Parkinson's Disease Rating Scale (UPDRS) before and
      after the treatment period. ELITE measures of postural stability and movement
      initiation revealed treatment-specific effects. In addition, UPDRS motor scores
      showed significant improvement only after behavioral treatment. We conclude that
      behavioral treatment in Parkinson's disease may improve motor disabilities in
      moderately advanced PD patients.

PMID- 9159725
TI  - Sensory and motor evoked potentials in multiple system atrophy: a comparative
      study with Parkinson's disease.
AB  - Somatosensory evoked potentials (SEPs) to median nerve stimulation and motor
      evoked potentials to transcranial magnetic stimulation (TMS) of the motor cortex
      were studied in 15 patients with multiple system atrophy (MSA) and compared with
      matched groups of 20 patients with idiopathic Parkinson's disease (PD) and of 20
      normal controls (NCs). No SEP latency or amplitude abnormalities were observed,
      and, in particular, the frontal N30 component was not significantly depressed. No
      differences in TMS threshold for evoking responses in relaxed or active thenar
      muscles were observed. The mean central motor conduction time was normal for the
      biceps brachii and opponens pollicis muscles and prolonged in the MSA group for
      the tibialis anterior muscle. Recording SEPs is not useful to differentiate MSA
      from PD, while the presence of central motor conduction abnormalities may bring
      into question the diagnosis of idiopathic PD.

PMID- 9159727
TI  - Torticollis due to disinhibition of the vestibulo-collic reflex in a patient with
      Steele-Richardson-Olszewski syndrome.
AB  - A patient with the clinical picture of Steele-Richardson-Olszewski syndrome and
      an unusual intermittent neck twisting is reported. He had virtually no voluntary
      ocular movements and only very slow, low-amplitude voluntary head movements.
      However, in response to optokinetic or vestibular stimulation, he developed full
      eye deviations in the direction of the slow phase of the expected nystagmus. No
      quick phases were observed, and the deviation outlasted the duration of the
      vestibular stimuli because of defective saccades. The head also turned fully
      during these stimuli, quicker than on attempted voluntary movements, and remained
      deviated similarly to the eyes. This suggests that the neck deviations in this
      patient were due to a disinhibited vestibulo-collic reflex and a disturbed head
      position resetting mechanism. Neck electromyographic responses in response to
      whole-body rotation indicated that the vestibulocollic reflex responsible for the
      torticollis in this patient had a short latency of approximately 30 ms.

PMID- 9159726
TI  - Comparison of swallowing function in Parkinson's disease and progressive
      supranuclear palsy.
AB  - Dysphagia is common in both Parkinson's disease (PD) and progressive supranuclear
      palsy (PSP). Although it is believed to be more common in PSP, there are no
      controlled data and no comparison of swallowing function between these two
      disorders. Our aim was to assess dysphagia and swallow function in patients with
      PSP and PD. Seven patients with PSP were matched to seven patients with PD on the
      basis of disease duration. Self-rated dysphagia, movement disorder disability,
      modified barium swallow results, and abnormalities noted on manometry of the
      lower esophageal sphincter, esophageal body, upper esophageal sphincter, and
      pharynx were compared between the two groups. Neither severity nor duration of
      dysphagia differed between the two groups. Patients with PSP had a significantly
      greater degree of disability [median (range) Hoehn & Yahr score, 4 (3-5) vs. 2 (1
      2); P < 0.002]. Manometric abnormalities were similar for the two groups. Oral
      phase abnormalities on modified barium swallow were significantly more frequent
      in PSP (four patients with PSP vs. no patients with PD; p < 0.005). Pharyngeal
      abnormalities did not differ. Modified barium-swallow scores correlated well with
      self-reported dysphagia severity for patients with PSP (r = 0.93; p < 0.05) but
      not for those with PD (r = 0.42; p = NS). The frequency of abnormalities noted
      during the oral phase was significantly increased in PSP. It is hypothesized that
      the sensory information conveyed due to this may account for the better
      correlation between symptoms and swallowing abnormalities and the belief that
      swallowing problems are more common in PSP.

PMID- 9159728
TI  - Effects of thalamic deep brain stimulation based on tremor type and diagnosis.
AB  - It has been suggested that deep brain stimulation (DBS) is less effective in
      alleviating proximal than distal postural arm tremor reduction is said to be less
      in essential tremor (ET) than in Parkinson's disease (PD). We analyzed blinded
      rater's tremor scores and subjects' disability ratings at 3-month follow-up to
      examine the effects of DBS based on tremor type (rest, kinetic, distal postural,
      proximal postural) and diagnosis (ET, PD). An independent examiner provided
      tremor scores using randomized videotaped footage of 19 ET and 10 PD subjects at
      baseline and at follow-up with DBS "on." Subjects provided self-ratings of
      disability at baseline and at follow-up. Comparisons of baseline and follow-up
      tremor scores and disability ratings were made using the Mann-Whitney U and
      Wilcoxon rank sum W test; correlation analyses were performed using Spearman rank
      order correlation test. There were significant and essentially equal improvements
      in tremor scores of test, kinetic, distal postural, and proximal postural tremor
      at follow-up. Only one subject had no improvement in tremor. Tremor improved
      significantly and to the same extent in ET and PD subjects in each position
      except "at rest," which was most improved in PD (p = 0.0003). ET and PD subjects
      did not differ in the extent of disability improvement. Improved disability
      correlated only with improved postural tremor scores; proximal postural and
      distal postural (r = 0.41, p = 0.03; r = 0.47, p = 0.01). DBS is effective in
      alleviating tremor and disability in both ET and PD. Resting, kinetic, distal
      postural, and proximal postural tremor can be reduced to an equal degree.
      However, DBS produces the greatest improvement in disability in association with
      improved postural tremor in both ET and PD.

PMID- 9159729
TI  - Adult-onset subacute sclerosing panencephalitis: case reports and review of the
      literature.
AB  - Subacute sclerosing panencephalitis (SSPE) is mainly thought of as a disorder of
      childhood and adolescence and may not be readily recognized when presenting later
      in life. Prior reports have suggested that adult-onset SSPE may have atypical
      features. We have added two cases to the existing literature on adult-onset SSPE,
      compared them with a more classic juvenile presentation, and extensively reviewed
      those reports that were published after the etiological link with the measles
      virus had been established. Adult-onset SSPE patients present at a mean age of
      25.4 years (range 20-35 years). They have a higher proportion of either negative
      history of measles exposure or undocumented history by the reporting authors.
      Those with available history of measles exposure tend to have it either earlier
      (younger than 3 years old) or later (after 9 years) than the usual childhood
      measles infection. Where the primary infection is known, unusually long measles
      to-SSPE intervals have been documented, ranging from 14 to 22 years. None of the
      cases followed measles vaccination. Visual symptomatology was very frequent, with
      8 of the 13 cases reviewed having a purely ophthalmological presentation; only 2
      patients presented with behavioral changes. Although the course of the disease
      was progressive and fatal in the majority, there appeared to be a higher rate of
      spontaneous remission as compared with childhood-onset SSPE. Myoclonus, spastic
      hemiparesis, bradykinesia, and rigidity were the predominant motor
      manifestations. Neuropathology revealed cortical and subcortical gray matter
      involvement preferentially of the occipital lobes, thalamus, and putamen. The
      importance of recognizing the spectrum of potential presentations of SSPE and
      providing an early diagnosis will increase as more effective treatments become
      available.

PMID- 9159730
TI  - Clinical features and management of two cases of encephalitis lethargica.
AB  - Two patients with presumed encephalitis lethargica are presented with clinical
      features suggestive of two forms of the disease described by Von Economo: One
      patient had a psychosis and a mute-akinetic syndrome associated with myoclonus.
      The second patient presented with a psychosis and fever, developing severe
      dyskinesias involving the mouth, trunk and limbs, together with respiratory
      irregularities and presumed hypothalamic disturbance and disturbance of
      consciousness. In both cases, initial cerebrospinal fluid (CSF) examination
      revealed an elevated white cell count (predominantly lymphocytes), elevated
      protein in case 2, and oligoclonal bands in both cases. Computed tomography (CT)
      brain scan was normal but in both cases EEG revealed diffuse slow wave activity.
      A 18F-Dopa positron emission tomography (PET) scan in case 2 was normal. The
      medical management of both patients is discussed. In case 1, L-Dopa improved the
      akinesia, while the myoclonus responded to clonazepam. In case 2, the severe
      dyskinesias failed to respond to a number of drugs, and she ultimately required
      paralysis to relieve her almost continuous movements. Both patients responded
      rapidly and dramatically to intravenous methylprednisolone. We suggest that
      steroid treatment should be considered in the acute phase of patients with
      features suggestive of encephalitis lethargica.

PMID- 9159731
TI  - Reflex myoclonus in cortical-basal ganglionic degeneration involves a
      transcortical pathway.
AB  - The short-latency reflex myoclonus that appears to be characteristic of cortical
      basal ganglionic degeneration (CBGD) was investigated in two patients.
      Stimulating the digital nerves of the middle finger caused exaggerated reflex
      activity in the first dorsal interosseus (FDI) muscle of that hand with a latency
      of 46-51 ms. Magnetic stimulation over the contralateral cortex, delivered 25 ms
      after the digital nerve stimulus, resulted in greater than expected facilitation
      of FDI, implying spatial summation. Poststimulus time histograms (PSTH) of
      individual FDI motor units indicated that this spatial summation was occurring
      "upstream" from the motoneurons. It is argued that this occurs at the motor
      cortex. Magnetic stimulation over the cortex in normal subjects results in short
      latency facilitation of the contralateral motoneurons followed by inhibition.
      This inhibition was less in the patients with CBGD. It is argued that this
      results from the loss of an intrinsic cortical and corticothalamic inhibitory
      mechanism.

PMID- 9159732
TI  - Familial cortical myoclonic tremor as a unique form of cortical reflex myoclonus.
AB  - Previously it was reported that some patients with tremor had the same
      electrophysiological findings as those seen in patients with cortical reflex
      myoclonus, and consequently the tremor was named "cortical tremor." In the
      present study, we examined six patients from three families with cortical tremor
      of relatively late onset. The inheritance pattern of cortical tremor was
      compatible with autosomal dominant trait. Those patients had relatively rhythmic
      involuntary movements (tremor) in the distal upper and lower limbs, especially
      during posture and/or fine movements. There was no cerebellar ataxia or dementia,
      and fits of loss of consciousness occurred only infrequently.
      Electrophysiologically, they had generalized spikes on electroencephalogram
      (EEG), giant cortical components of somatosensory evoked potential, an enhanced
      long-loop reflex (C-reflex), and cortical spikes preceding the rhythmic jerk
      demonstrable by the jerk-locked back averaging method, thus fulfilling the
      criteria of cortical reflex myoclonus. Furthermore, they had slow negative EEG
      shift starting 1-2 s prior to voluntary movements, suggesting that, as opposed to
      the conventional form of progressive myoclonus epilepsy (PME), the cerebellar
      efferent input to the motor cortices was normal. These clinical and
      electrophysiological pictures are distinct from those of familial essential
      tremor, familial essential myoclonus, or the conventional form of PME, and the
      term "familial cortical myoclonic tremor" will represent the clinical and
      electrophysiological features of this unique entity most appropriately.

PMID- 9159733
TI  - Clonic perseveration following thalamofrontal disconnection: a distinctive
      movement disorder.
AB  - We describe four patients who developed asymmetrical, rhythmic, stereotyped, and
      repetitive movements of the upper and lower limbs hours to days after infarction
      that involved the thalamus and/or basal ganglia. The movements appeared to occur
      spontaneously and were initially labeled as focal motor seizures, ballism, or
      tremor; they could however, be induced by passive movement of the limbs. The
      movements most commonly observed were scratching or rubbing movements of the
      hands that were of such persistence as to cause trauma to the skin; in the lower
      limbs, the heel was run up and down the bed sheet, often until it bled. The
      movements were part of a syndrome characterised initially by a reduced level of
      consciousness and followed by aspontaneity, usually with mutism and frontal
      release signs. One patient who had relatively preserved cognition and language
      repeated words or phrases again and again when encouraged to speak, but had no
      difficulty changing responses appropriately to different cues. In drawing, he
      overwrote each figure but could change the figure on command. The distinctive
      movement disorder in these patients was due to clonic perseveration. We suggest
      that clonic perseveration results from disconnection of prefrontal cortico-basal
      ganglia-thalamo-cortical loops that are important for the termination of motor
      plans. Clonic perseveration should be recognised as a movement disorder following
      thalamic lesions.

PMID- 9159734
TI  - Impairments of movement kinematics in patients with Huntington's disease: a
      comparison with and without a concurrent task.
AB  - This study aimed to quantify the efficiency and smoothness of voluntary movement
      in Huntington's disease (HD) by the use of a graphics tablet that permits
      analysis of movements profiles. In particular, we aimed to ascertain whether a
      concurrent task (digit span) would affect the kinematics of goal-directed
      movements. Twelve patients with HD and their matched controls performed 12
      vertical zig-zag movements, with both left and right hands (with and without the
      concurrent task), to large or small circular targets over long or short extents.
      The concurrent task was associated with shorter movement times and reduced right
      hand superiority. Patients with HD were overall slower, especially, with long
      strokes, and had similar peak velocities for both small and large targets, so
      that controls could better accommodate differences in target size. Patients with
      HD spent more time decelerating, especially with small targets, whereas controls
      allocated more nearly equal proportions of time to the acceleration and
      deceleration phases of movement, especially with large targets. Short strokes
      were generally less force inefficient than were long strokes, especially so for
      either hand in either group in the absence of the concurrent task, and for the
      right hand is its presence. With the concurrent task, however, the left hand's
      behavior changed differentially for the two groups; for patients with HD, it
      became more force efficient with short strokes and even less efficient with long
      strokes, whereas for controls, it became more efficient with long strokes.
      Controls may be able to divert attention away from the inferior left hand,
      increasing its automaticity, whereas patients with HD, because of disease, may be
      forced to engage even further online visual control under the demands of a
      concurrent task. Patients with HD may perhaps become increasingly reliant on
      terminal visual guidance, which indicates an impairment in constructing and
      refining an internal representation of the movement necessary for its effective
      execution. Basal ganglia dysfunction may impair the ability to use internally
      generated cues to guide movement.

PMID- 9159735
TI  - A controlled trial of fluoxetine in nondepressed patients with Huntington's
      disease.
AB  - To examine the antidepressant specificity of fluoxetine in Huntington's disease
      (HD), we carried out a randomized, double-blind, placebo-controlled trial of this
      medication in nondepressed HD patients. Thirty patients with early HD who were
      depressed (Hamilton Depression Inventory < 16) were randomized to placebo (N =
      13) or fluoxetine 20 mg/day (N = 17) and were followed up for 4 months. Outcome
      measures included changes in total functional capacity (TFC) and in standardized
      neurological, cognitive, and behavioral ratings. After adjustment for the higher
      education level found in the placebo group at baseline, no differences between
      the treatment groups were found in TFC, neurological, or cognitive ratings.
      Fluoxetine-treated patients did show a slight reduction in agitation and in the
      need for routine. Although fluoxetine may be a useful antidepressant in depressed
      HD patients, it failed to exert substantial clinical benefits in nondepressed HD
      patients.

PMID- 9159736
TI  - Dopamine agonist treatment of Tourette disorder in children: results of an open
      label trial of pergolide.
AB  - This exploratory study was meant to determine the effect of the dopamine (DA)
      agonist pergolide on Gilles de la Tourette syndrome (GTS) in children and
      adolescents and to ascertain correlates of pergolide response. Thirty-two
      outpatients, aged 7-19 years, were systemically assessed in a neuropsychiatric
      clinic for the presence of GTS and comorbid disorders. After a 6-week open-label,
      fixed-flexible dosing schedule, response to pergolide on standard GTS severity
      outcome measures was assessed. Overall, 75% of patients (24/32) had a > 50% drop
      in their tic severity rating from baseline with a mean treatment dosage of 177 +/
      61 micrograms/day. Highly significant (p = 0.0001) baseline to week 6
      differences were demonstrated in all tic symptom measures. The presence of
      restless legs syndrome (RLS) comorbidity (59%) was highly associated with a
      positive response. These results suggest DA agonism as a strategy, and pergolide
      in particular, may be a practical form of therapy for GTS. Response predictors of
      patient comorbid RLS argue for its further study with regard to GTS.

PMID- 9159737
TI  - 6-Pyruvoyl-tetrahydropterin synthase deficiency with generalized dystonia and
      diurnal fluctuation of symptoms: a clinical and molecular study.
AB  - We report the case of a 44-year-old woman with a partial 6-pyruvoyl
      tetrahydropterin synthase (6-PTS) deficiency, whose predominant clinical symptom
      was generalized dystonia with marked diurnal fluctuation. Dystonia was present in
      the eyelids, oromandibular region, trunk, and extremities (Meige syndrome plus
      double hemiplegia-like dystonia). A marked and sustained positive response to
      levodopa was observed. A molecular genetic study revealed a homozygous mutation
      (I114V) in the 6-PTS gene. This study indicates that genetic abnormality in the 6
      PTS gene may be a hereditary dystonia disorder. We speculate that our patient has
      residual 6-PTS activity in the central nervous system, such as in the liver, and
      we suggest that residual, but insufficient production of tetrahydrobiopterin may
      play an important role in causing diurnal fluctuation of symptoms.

PMID- 9159738
TI  - Evidence for a new spinocerebellar ataxia locus.
AB  - The autosomal dominant ataxias (ADA) are a diverse group of multisystem,
      neurodegenerative disorders characterized by mutations at several chromosomal
      loci (SCA types 1-5, SCA type 7, DRPLA). We excluded all the known SCA loci by
      mutational and linkage analyses is an American family of British origin with ADA
      and document that an additional ataxia locus must exist. The clinical
      characteristics and ethnic origin of our family are similar to the British Drew
      family of Walworth with the SCA type 3 mutation and differ from other families
      without a known ataxia locus. Individuals in our family and the Drew family
      initially show signs of ataxia but may develop variable degrees of
      ophthalmoplegia, Parkinsonian features and central demyelination. The phenotypic
      diversity in families without a known ataxia locus suggests that there may be
      several other undefined ataxia loci.

PMID- 9159739
TI  - Mitochondrial respiratory chain function in multiple system atrophy.
AB  - Multiple system atrophy (MSA) is a clinico-pathological entity distinct from
      idiopathic Parkinson's disease (PD) that is responsible for 5-10% of cases of
      parkinsonism. Degeneration of nigral neurones is a feature of both diseases. A
      specific deficiency of mitochondrial complex I activity has been found in PD
      substantia nigra. We have analysed mitochondrial function in substantia nigra and
      platelets from MSA patients to identify any respiratory chain defect in this
      disorder and to determine its tissue specificity. As our MSA patients had been on
      L-DOPA, we also sought to establish whether this treatment could cause the
      complex I defect as seen in PD. We found no significant difference in respiratory
      chain activity corrected for mitochondrial mass between control and MSA patients
      in either of the tissues studied. These results provide a biochemical dimension
      to the differences between MSA and idiopathic PD. In addition, the fact that L
      DOPA failed to induce a complex I defect in MSA substantia nigra suggests that
      this treatment is unlikely to cause the complex I deficiency in PD, without
      additional factors that may operate in PD.

PMID- 9159740
TI  - Long-term results with cisapride in Parkinson's disease.
AB  - In this study, we examined whether there is a long-term effect of cisapride on
      colonic transit in Parkinson's disease. Twenty-five patients (11 women, 14 men;
      average age, 64.4 years; moderate symptoms) were studied and treated initially
      with cisapride, 5 mg, twice a day, and after the first week with cisapride, 10
      mg, twice a day. Colonic transit was measured by radioopaque markers at various
      stages: after 1 week, 6 months, and 1 year. In untreated patients, transit took
      131 h; after 1 week with cisapride, it was accelerated to 81 h. After 6 months,
      colonic transit time amounted to 99 and 118 h, respectively, after 1 year.
      Cisapride seems to be highly effective initially. After 6 months, a significant
      but reduced effect was seen, and after 1 year, only a small effect could be
      demonstrated.

PMID- 9159741
TI  - G/A1947 polymorphism in catechol-O-methyltransferase (COMT) gene in Parkinson's
      disease.
AB  - High and low catechol-O-methyltransferase (COMT) activity is significantly
      determined by thermostability, which is caused by a valine/methionine108
      polymorphism associated with polymorphic G/A1947 bases, in exon 4 of the COMT
      gene. Our allelic association study on this polymorphism did not find any
      statistically significant difference between our Chinese Parkinson's disease and
      that of control subjects. These results show that this polymorphism and hence the
      thermostability of COMT enzyme are not related to a risk of developing
      Parkinson's disease.

PMID- 9159742
TI  - Posttraumatic movement disorders after moderate or mild head injury.
AB  - We examined the occurrence of posttraumatic movement disorders after moderate or
      mild head injury with a three-level follow-up study including questionnaires,
      telephone interviews, and personal examinations 4-6 years after the trauma (mean
      5.2 years). Sixteen of 158 patients (10.1%) for whom a detailed follow-up was
      available had developed movement disorders most probably related to
      craniocerebral trauma. The most frequent finding was a low-amplitude
      postural/intention tremor that appeared to resemble enhanced physiological or
      essential tremor. Twelve patients reported transient tremor, two patients had
      persistent tremor, one patient had transient tremor and persistent hyperekplexia,
      and another patient had mild persistent cervical myoclonic twitches. Overall, the
      movement disorder was transient in 12 patients (7.6%) and persisted in only 4
      patients (2.6%). These movement disorders were not disabling and did not require
      medical therapy. Taking into account possible bias by selection of the sample
      group, the frequency of movement disorders secondary to moderate or mild head
      trauma might be lower than 10.1%. Posttraumatic movement disorders occurred
      significantly more often in the group of patients with Glasgow Coma Scores
      between 9 and 14 than in those with a score of 15. Severe movement disorders such
      as low-frequency kinetic tremor or hemidystonia were not identified in this
      survey.

PMID- 9159743
TI  - Midbrain tremor and hypertrophic olivary degeneration after pontine hemorrhage.
AB  - A severe rest tremor arose in a patient's right arm 9 months after a pontine
      tegmental hemorrhage. Magnetic resonance studies at 4 and 10 months showed
      residual hemosiderin in the pons and increasing hypertrophic olivary degeneration
      (HOD) affecting primarily the left olive. The tremor was refractory to
      pharmacotherapy (clonazepam, propranolol, and levodopa), but was reduced after
      implantation of a thalamic stimulator device. Although pontine hemorrhage is
      among several common causes of HOD, it has not previously been appreciated as a
      cause of midbrain ("rubral") tremor. A disynaptic dentatorubroolivary tract
      associated with tremor and monosynaptic dentatoolivary tract associated with HOD
      may both be components of the rubroolivocerebellorubral loop implicated in
      midbrain tremor. Their proximity makes the combination of tremor and HOD after
      pontine tegmental damage plausible and even likely.

PMID- 9159744
TI  - Electrophysiological observations in idiopathic opsoclonus-myoclonus syndrome.
AB  - To supplement existing knowledge regarding the pathophysiology of the opsoclonus
      myoclonus syndrome, electrophysiological findings are reported in three patients
      with idiopathic opsoclonus-myoclonus. Surface electromyography (EMG) revealed <
      100-ms synchronous discharges correlating with the clinical myoclonus. Short
      duration EMG discharges, with no back-averaged cortical correlate, normal gross
      electroencephalogram, and no exaggerated responses with either evoked potential
      testing or long latency EMG responses were observed. The clinical and
      electrophysiological findings we describe are consistent with a brainstem origin
      of the myoclonus in this syndrome, with concurrent abnormalities in cerebellar
      circuits, similar to those described for paraneoplastic cases. The constellation
      of these electrophysiological findings differentiates the myoclonus in these
      patients from other clinical myoclonic entities.

PMID- 9159745
TI  - Cervical dystonia associated with tumors of the posterior fossa.
AB  - Cervical dystonia was associated with posterior fossa tumors in three patients.
      The onset of dystonia paralleled the appearance of other focal neurologic signs.
      All patients had extraaxial tumors located in the cerebellopontine angle that
      were removed via suboccipital approaches. The tumors were identified as
      schwannomas arising from the glossopharyngeal nerve and from the vagus/accessory
      nerves; and a meningioma. Postoperatively, the cervical dystonia improved
      markedly during a period of 8 years in one patient, and it remitted completely
      within 1 year in another patient. In the third patient, cervical dystonia
      persisted. The combination of the clinical findings and the temporal relationship
      of their appearance suggest a causal association between the posterior fossa
      tumors and cervical dystonia in three cases. Possible pathogenic mechanisms are
      reviewed.

PMID- 9159746
TI  - [123I]beta-CIT single-photon emission tomography in DOPA-responsive dystonia.
AB  - The radiotracer [123I]beta-CIT is a sensitive marker of dopamine uptake sites
      that can be used to visualize dopaminergic nerve endings in vivo in the human
      brain. We report on [123I]beta-CIT single-photon emission computed tomography
      (SPECT) findings in a patient with DOPA-responsive dystonia (DRD). [123I]beta-CIT
      SPECT showed a striatal radiotracer uptake in the upper range of normal,
      indicating intact dopamine transporters and structural integrity of nigrostriatal
      neurons. This differentiates DRD from clinically similar cases with juvenile
      onset parkinsonism with dystonia that have a considerable poorer prognosis.
      [123I]-beta-CIT SPECT may provide a method equally as useful as fluorodopa
      positron emission tomography in DRD.

PMID- 9159747
TI  - Magnetic brain stimulation in multiple system atrophy.

PMID- 9159748
TI  - Dopa-responsive, nonprogressive juvenile parkinsonism: report of a case.

PMID- 9159749
TI  - Acanthocytosis and spinocerebellar degeneration: a new association?

PMID- 9159751
TI  - Adult-onset subacute sclerosing panencephalitis first seen as craniocervical
      myoclonus.

PMID- 9159752
TI  - Chorea resulting from paraneoplastic encephalitis.

PMID- 9159753
TI  - Treatment of spasmodic torticollis with mexiletine: a case report.

PMID- 9159750
TI  - Tardive jaw tremor.

PMID- 9159754
TI  - Abnormal movements in a patient with reflex sympathetic dystrophy.

PMID- 9159755
TI  - Another case of Hashimoto's encephalopathy.

PMID- 9159756
TI  - A 10-year follow-up--genotypic analysis disproves phenotypic classification.

PMID- 9159757
TI  - Neuronal responses at the sight of objects in monkey basal forebrain subregions
      during operant visual tasks.
AB  - The basal forebrain appears to be important in cognitive function. It has been
      suggested that this region is composed of several cholinergic cell groups, mainly
      the medial septum, the diagonal band of Broca, and the nucleus basalis of
      Meynert. To elucidate the functional differences between these subregions, we
      have recorded single-unit activity from the periventricular areas involving the
      medial septum, the diagonal band of Broca (ms/dbB), and the substantia innominata
      (SI), including the nucleus basalis of Meynert, of an object-discriminating
      monkey. Of 226 ms/dbB and 439 SI neurons analyzed, 36 (15.9%) and 115 (26.2%),
      respectively, responded to the sight of some complex object. Thirteen (5.8%)
      ms/dbB and 80 (18.2%) SI neurons responded to virtually all objects and the ratio
      of these neurons in the SI was higher than that in the ms/dbB. The other 23
      (10.2%) ms/dbB and 35 (8.0%) SI neurons responded preferentially to one or two of
      three categories (rewarding, aversive, or meaningless) of familiar or to
      unfamiliar objects, and response selectivity to one category of the ms/dbB
      neurons (15; 6.6%) was higher than that to the SI neurons (14; 3.2%). The results
      suggest that the SI, including the nucleus basalis of Meynert, may encode visual
      information about objects more broadly and participate more fully in visual
      attention than the ms/dbB region, which may be more closely related to learning.

PMID- 9159758
TI  - Chicks injected with antisera to either S-100 alpha or S-100 beta protein develop
      amnesia for a passive avoidance task.
AB  - The cellular expression of S-100 beta protein is upregulated in Alzheimer's
      disease and in Down's syndrome, and this protein has been implicated in memory
      related processes in laboratory animals. However, the possibility that the alpha
      subunit of S-100 is also involved in memory has not yet been examined. In the
      present study, day-old black Australorp white Leghorn cockerel chicks (Gallus
      domesticus) received injections of monoclonal antisera to S-100 alpha (1:50) or S
      100 beta (1:500) into each hemisphere immediately after training on a one-trial
      passive avoidance task. The chicks displayed significantly lower retention levels
      than control birds that had been injected with antisera to carbonic anhydrase, or
      with saline (p < .01). S-100 alpha antisera had an amnestic effect when injected
      between 0 and 20 min after training, with memory deficits occurring from 30 min
      post-learning, at the point of transition between the A and the B phases of the
      Gibbs-Ng intermediate memory stage. By contrast, the S-100 beta antisera needed
      to be injected either 5 min before or immediately after training and produced
      amnesia 10 min earlier, at the start of the A phase of the intermediate memory
      stage. We conclude that the two subunits of the S-100 protein are required at
      different points in the sequence of events leading to the consolidation of
      passive avoidance memory.

PMID- 9159759
TI  - Inhibition of intermediate-term memory following passive avoidance training in
      neonate chicks by a presynaptic cholinergic blocker.
AB  - The effects of a specific presynaptic cholinergic antagonist, toosendanin, on
      memory formation following a passive avoidance training experience in day-old
      chicks was investigated. Bilateral injection of toosendanin into the
      neostriatal/hyperstriatal region of the chick forebrain produced memory
      impairment in a dose-dependent manner. Retention deficits were apparent from 20
      min following training in chicks treated with toosendanin, regardless of the
      injection time relative to training. Chicks that received injections of the drug
      at corresponding times prior to retention tests showed normal retention levels,
      suggesting that toosendanin has no effect on performance and memory retrieval.
      These results indicate an involvement of cholinergic transmission during an early
      stage of memory formation.

PMID- 9159760
TI  - The effects of selective cholinergic basal forebrain lesions and aging upon
      expectancy in the rat.
AB  - The effects of selective cholinergic cell loss within the basal forebrain (BF)
      were determined using a task that requires shifting of attention between two
      visual stimuli. Discriminability between two stimuli and response bias were
      determined in young and old F-344 rats given BF injections of IgG-192 saporin
      (100 ng). The lesion reduced ChAT activity in the frontal and parietal cortices,
      hippocampus, and olfactory bulbs. The lesion did not significantly alter Na+/K(+)
      ATPase activity in cortex, hippocampus, or olfactory bulbs, or endogenous levels
      of neuropeptide Y and neurokinin B within the BF. The BF lesions impaired both
      stimulus discriminability and response bias in young and old rats. The BF lesions
      had a significantly greater effect upon stimulus discriminability and response
      bias in aged rats, compared to young rats, only when the stimulus duration was
      very brief, i.e., when the task was most difficult to solve. At longer stimulus
      durations, aging and lesions showed no interaction. The results suggest that the
      selective loss of cholinergic cells in the BF, but not normal aging, impairs the
      ability to discriminate between independent sensory stimuli. The loss of these
      cells confers a response bias in simple operant tasks involving motor responses
      to reward-related visual stimuli.

PMID- 9159761
TI  - Differential effects of global ischemia on delayed matching- and non-matching-to
      position tasks in the water maze and Skinner box.
AB  - In order to assess effects of global ischemia in tasks of spatial learning and
      working memory, male Wistar rats were subjected to four vessel occlusion (4 VO)
      for periods of 5, 10, and 20 min and compared with sham-operated controls over
      four test phases, from 6 to 54 weeks after surgery. Rats were assessed on
      acquisition in the water maze, a task that is sensitive to ischemic impairments,
      before testing in Skinner box and water maze working memory tasks, which both
      require the short-term storage of information, but make different demands on
      spatial information processing. Phases 1 and 3 assessed spatial learning in a
      standard water maze procedure (12 and 10 training days, 2 trials/day with a 10
      min intertrial interval: ITI). Phase 2 involved training and testing in delayed
      non-matching-to-position task in the Skinner box, with delays of 2-10 s between
      the information and choice stages. Phase 4 examined working memory in a water
      maze delayed matching-to-position task with 4 trials/day, an ITI of 30 s, and a
      novel platform position on each day. Ischemic rats showed duration-related
      impairments in water maze acquisition and working memory, but not in the less
      spatially demanding Skinner box task. Since water maze acquisition deficits were
      seen both before and after testing in the Skinner box the lack of effect cannot
      be attributed to time or to prior training. Ischemic deficits were more marked in
      Phase 3 than in Phase 1 of acquisition, suggesting that impairment may be
      progressive. Histological assessment showed that cell loss was largely confined
      to the hippocampal CA1 field and was linearly related to duration of occlusion.
      At the maximal level of loss (5.7 mm before the interaural line) the 20-min group
      showed 90% loss, the 10-min group 60% loss, and the 5-min group, which did not
      differ from controls, less than 10% loss. Only the 20-min group showed
      significant damage beyond the CA1 field, ranging from 30-40% loss in the CA3
      field to 5% loss in one striatal area. No cortical damage was seen. The extent of
      CA1 cell loss correlated modestly with water maze acquisition (Phase 3) and
      working memory scores, but not with trials to criterion in the Skinner box task.
      There were significant correlations between different measures both within and
      between water maze tasks, but not Skinner box tasks, suggesting that the two
      types of procedure engaged different cognitive processes. The results indicate
      that the intrahippocampal damage induced by 4 VO impaired tasks which required
      processing of allocentric spatial information, but did not impair the storage of
      limited spatial information in working memory.

PMID- 9159762
TI  - Left syringeal dominance in testosterone-treated female canaries.
AB  - Male canaries (Serinus canaria) produce most of their song syllable types on the
      left side of the syrinx, the two-sided vocal organ. Female canaries treated with
      testosterone propionate begin to sing in a male fashion, a behavior seldom seen
      in untreated females. To learn whether syringeal dominance occurs in testosterone
      treated female canaries, we deactivated either the right or the left side of the
      syrinx by severing the tracheosyringeal nerve on that side. Recordings of the
      birds' songs were made before and after the nerve cut, and song analysis was
      based upon visual comparisons of sound spectrograms. Pre- and post-operative
      syllable types were identified by their frequency structures and repetition
      rates. Six of eight birds displayed clear left dominance as assessed by nerve
      cuts; therefore, we concluded that most, but not all, female canaries generate
      the majority of their syllable types with the left syrinx.

PMID- 9159763
TI  - Facilitation of a distributed shuttle-box conditioning with posttraining
      intracranial self-stimulation in old rats.
AB  - Old Wistar rats (16-17 months) were trained in a two-way active avoidance task
      for 5 consecutive days (10 trials/day). Immediately after each training session a
      lateral hypothalamic intracranial self-stimulation session (ICSS group) or a sham
      treatment session (Control group) was given to the animals. Long-term retention
      was tested 7 days after the last acquisition session. ICSS treatment led to a
      significant improvement in acquisition. In the long-term retention session the
      level of avoidance in both groups was similar to that achieved in the last
      acquisition session, although differences among groups failed to reach
      statistical significance. These results are compared with those obtained in
      previous experiments with young adult rats. While ICSS facilitated the process of
      acquisition in both young and old rats (however, it was much more powerful in
      young animals), further experiments are needed to elucidate whether this effect
      is long-lasting in old rats, as occurs in young adult subjects.

PMID- 9159764
TI  - Reversal of relative thresholds for synaptic facilitation and increased
      excitability induced by serotonin and tail nerve stimulation in Aplysia sensory
      neurons.
AB  - Tail shock induces reflex sensitization in Aplysia and, in parallel, induces a
      number of modulatory effects in central neurons, such as increased excitability
      in tail sensory neurons (SNs) and facilitation of synaptic transmission from SNs
      to motor neurons. Both of these modulatory effects are mimicked by exogenous
      application of serotonin (5HT) or electrical stimulation of the tail nerve P9. In
      the present study we examined the activation thresholds for increased
      excitability and synaptic facilitation induced by either 5HT or P9 stimulation.
      We found that the concentration of 5HT sufficient to produce a significant
      increase in excitability produced no significant synaptic facilitation and,
      conversely, that the intensity of nerve stimulation sufficient to produce
      significant synaptic facilitation produced no excitability changes. This reversal
      of relative thresholds for these modulatory effects may reflect the differential
      access of exogenous 5HT and endogenous 5HT (released by tail nerve stimulation)
      to the SN cell body and synaptic terminals, respectively.

PMID- 9159765
TI  - Status of lipids as a risk factor for stroke.
AB  - There is mounting epidemiologic evidence to support the relationship of lipids as
      a risk factor for ischemic stroke. We review epidemiologic and pathophysiologic
      evidence for such a link. Treatment of hyperlipidemia is addressed within the
      context of overall cardiovascular disease risk but also for stroke prevention.

PMID- 9159766
TI  - Cerebrovascular disease mortality in Spain, 1955-1992: an age-period-cohort
      analysis.
AB  - The purpose of this study was to assess the contributions of period and birth
      cohort effects to changes in cerebrovascular disease (CVD) mortality in Spain
      over the period 1955-1992. Poisson regression models were fitted to age-and sex
      specific CVD mortality rates obtained from National Vital Statistics. In the
      period 1955-1975, CVD mortality remained stable. In the period 1975-1992, CVD
      mortality declined by 54% (rate ratio, RR: 0.46; 95% confidence interval, CI:
      0.43-0.49) in males and 62% (RR: 0.38; 95% CI: 0.34-0.42) in females. The cohort
      effect was very small up to the generation born in 1905, moving clearly downward
      thereafter. CVD mortality for subjects born in the period 1945-1949 was lower
      than for those born in the period 1905-1909 by 68% (RR: 0.32; 95% CI:0.16-0.63)
      in males and 82% (RR: 0.18; 95% CI: 0.07-0.45) in females. Among the possible
      partial explanations for these effects are the decline in ischemic heart disease
      and rheumatic fever mortality, the drop in salt and alcohol intake, the reduction
      in smoking among males and blood pressure among females, and the widespread use
      of antihypertensive treatments in Spain over the last 20 years.

PMID- 9159767
TI  - The Washington Heights-Inwood Genetic Study of Essential Tremor: methodologic
      issues in essential-tremor research.
AB  - Essential tremor (ET) is the most prevalent movement disorder. It is unknown to
      what extent ET clusters within families, and the role of genetic susceptibility
      in etiology of ET has not been adequately investigated at the population level.
      The problem is largely methodological, with few well-designed studies. The
      Washington Height-Inwood Genetic Study of ET, begun in 1955, is designed to
      investigate the genetics of ET using a methodology that has not been applied to
      ET research to date. Part of the design includes a new set of clinical and
      electrophysiological diagnostic criteria for ET; the present paper describes this
      novel study design.

PMID- 9159768
TI  - Survival in early onset dementia: effects of urbanization and socio-economic
      deprivation.
AB  - We estimated survival of patients with early onset Alzheimer's disease (AD) or
      vascular dementia (VaD) presenting to psychiatric hospitals in Scotland (1974
      1988) and related this to age, gender and socio-economic variables. Hospital
      records of 1794 early onset dementia patients were reviewed. We identified 451
      patients with early onset AD and 384 with VaD. Survival to death was calculated
      from symptom onset and presentation. Small geographical areas (postcode sectors)
      were classified by urban/rural category and deprivation score. Five-year survival
      from presentation of early onset AD was 32% for men and 43% for women compared to
      22% for men and 36% for women with VaD. We conclude that increased age at
      presentation was associated with shorter survival in early onset AD and VaD.
      Socio-economic deprivation was associated with longer survival in VaD. The
      effects of urban/rural score were accounted for by the major effects of socio
      economic deprivation.

PMID- 9159769
TI  - Reliability of the Modified Mini-Mental State Examination in the context of a two
      phase community prevalence study.
AB  - Data collected through the Canadian Study of Health and Aging were analyzed to
      estimate the reliability of the Modified Mini-Mental State (3MS) Examination when
      used in the context of a two-phase community prevalence study. During the
      screening phase of the study, subjects were tested in their home by a lay
      interviewer, either in English or French. All subjects scoring 77 or under on the
      3MS and a sub-sample of those scoring over 77 were reassessed by a nurse during a
      clinical examination, following which subjects were classified as normal,
      cognitively impaired but not demented, or demented. Results indicate substantial
      reproducibility of the 3MS, slightly higher than that of the Mini-Mental State
      Examination from which it is derived. The english versions of these tests appear
      slightly more reproducible than their French counterparts.

PMID- 9159770
TI  - The prevalence and severity of white matter lesions, their relationship with age,
      ethnicity, gender, and cardiovascular disease risk factors: the ARIC Study.
AB  - White matter lesions (WMLs) detected by cerebral magnetic resonance imaging (MRI)
      are putatively a consequence of cerebral hypoperfusion or ischemia. We
      investigated the prevalence, severity and correlates of WMLs in a population
      based sample of 1,920 African-American and European-American men and women aged
      55-72 years, during the second follow-up examination of the Atherosclerosis Risk
      in Communities Study. The spin density images from 1.5-tesla MRI scans were used
      to define WMLs using a 0-9 scale with 0 for normal and 9 for most severe WMLs.
      Age was positively associated with the prevalence (percent) and severity of WMLs.
      African-Americans had lower overall prevalence of WMLs, but a higher prevalence
      of relatively more severe WMLs, than European-Americans. After adjusting for age,
      sex, and ethnicity, WMLs were significantly associated with smoking, lower
      education, hypertension, systolic blood pressure, and pulse pressure, and weakly
      associated with diastolic blood pressure. The associations of smoking, alcohol
      intake, systolic and diastolic blood pressure, pulse, pressure, and hypertension
      were stronger in African-Americans than in European-Americans (p < 0.15 for
      interactions by ethnicity). This population-based MRI study documents significant
      relationships between several cardiovascular disease risk factors and WMLs. The
      findings suggest that such factors play a role in the pathogenesis of WMLs, an
      elements linked to hypoperfusion and/or fluid accumulation, which presumably lead
      to WMLs. African-Americans exhibited both a higher proportion of normal white
      matter and a higher proportion of relatively more severe WMLs than European
      Americans.

PMID- 9159771
TI  - Practical guidelines in the use of symptom validity and other psychological tests
      to measure malingering and symptom exaggeration in traumatic brain injury cases.
AB  - The detection of malingering or symptom exaggeration has become an essential
      component in forensic neuropsychological evaluations, particularly in cases
      involving personal injury claims. Symptom Validity Tests refer to those measures
      that can be utilized to detect test performance that is so poor that it is below
      the level of probability, often times even among brain-damaged populations. This
      article outlines legal standards for expert testimony in regard to forensic
      neuropsychological personal injury evaluations. The article provides an outline
      of specific Symptom Validity Tests and Indicators, and reviews literature
      supporting test sensitivity and validity. In addition, the use of symptom
      checklists and questionnaires is discussed, as well as the appropriate use of
      Symptom Validity Tests and Indicators to establish the presence or absence of
      malingering or symptom exaggeration.

PMID- 9159773
TI  - Reader disagrees with method of declogging feeding tubes.

PMID- 9159774
TI  - Commentary: patient counseling and education.

PMID- 9159775
TI  - An active patient and family education committee serves patient's needs.

PMID- 9159776
TI  - Nurses teach complete decongestive physiotherapy for lymphedema management.

PMID- 9159772
TI  - Can we learn from the clinically significant face processing deficits,
      prosopagnosia and Capgras delusion?
AB  - This review describes two clinically significant face processing deficits,
      prosopagnosia and Capgras delusion, and provides new knowledge about the face
      recognition process by a convergence of empirical findings. These empirical
      findings are structured around two questions that are reviewed from the
      perspectives of the two deficits. First is the question of hemispheric
      specificity, which inquires into the degree of each hemisphere's contribution to
      the face recognition process. Second is the question of dual neural pathways,
      which addresses the possibility that the face recognition process proceeds along
      two parallel pathways in the brain. Findings from the hemispheric specificity
      studies reinforce the current view that right hemispheric involvement is
      necessary for face recognition while left hemispheric involvement is minimal.
      Findings from the dual neural pathways studies reinforce the plausible but yet
      unproven hypothesis that two neural pathways pass information from the visual
      association cortex in the occipital lobe toward the temporal lobes and limbic
      system when faces are seen and recognized. These findings, which also indicate
      that each of the dual neural pathways carries different, nonredundant
      information, could be instrumental in showing that the pathways play different
      roles in the manifestations of the clinically significant face processing
      deficits, prosopagnosia and Capgras delusion.

PMID- 9159777
TI  - Cross-training of homecare and hospice nurses promotes continuity of care.

PMID- 9159778
TI  - Radiation oncology department develops patient education program.

PMID- 9159779
TI  - Triple check procedure prevents chemotherapy errors.

PMID- 9159780
TI  - Patient satisfaction with 23-hour "short-stay" observation following breast
      cancer surgery.
AB  - PURPOSE/OBJECTIVES: To determine what problems patients undergoing breast cancer
      surgery experienced following discharge after participating in a 23-hour short
      stay observation program and to explore their perceptions of the short-stay
      experience. DESIGN: Descriptive and exploratory. SETTING: A comprehensive cancer
      center in an urban setting. SAMPLE: 52 women undergoing modified radical
      mastectomy, segmental mastectomy (lumpectomy) with axillary node dissection,
      simple mastectomy, or other breast procedures. METHODS: Telephone interviews 24
      72 hours and 7-10 days after discharge using questionnaires developed by the
      investigators. MAIN RESEARCH VARIABLES: Postoperative difficulties, satisfaction
      with pain relief, positive and negative aspects of the short-stay process, and
      discharge to home. FINDINGS: Most patients had no difficulty with drain and
      incision care (84%), reported satisfactory analgesic relief with their prescribed
      medications (> 95%), and were prepared to leave the hospital on first
      postoperative day (85%). Patient education and care provided by physicians and
      nurses were highly rated. Although most responses were highly favorable, some
      women desired longer hospitalization (21%) and greater privacy while on the
      observation unit (13%). CONCLUSIONS: By coordinating inpatient and outpatient
      services, short-stay observation following breast cancer surgery can be
      accomplished in a safe environment that patients perceive to be satisfactory and
      of high quality. IMPLICATIONS FOR NURSING PRACTICE: Short-stay observation is
      feasible for appropriately prepared postoperative patients who normally are
      managed on traditional impatient units.

PMID- 9159781
TI  - Impact of parental anxiety on child emotional adjustment when a parent has
      cancer.
AB  - PURPOSE/OBJECTIVES: To describe the relationships among parent anxiety, child
      anxiety, and emotional adjustment in children who have a parent with cancer.
      DESIGN: Correlational. SETTING: A large cancer center in the southeastern United
      States. SAMPLE: Thirty-three child/parent with cancer dyads. METHODS: Research
      packets were mailed to child/parent dyads who agreed to participate in the study.
      Parents completed a demographic questionnaire, a Spielberger State-Trait Anxiety
      Scale, and a Personality Inventory for Children (PIC). Children completed the
      child version of the Spielberger State-Trait Anxiety Scale. MAIN RESEARCH
      VARIABLES: Parent anxiety, child anxiety, and child adjustment. FINDINGS:
      Children who have a parent with cancer and parents who have experienced cancer
      report significantly higher state and trait anxiety compared to a normed
      population sample. Parental reports on the PIC indicated that latency-aged
      children (i.e., 6-12 years) showed significantly greater internalization and
      somatic symptoms compared to the sample norm. Parent state anxiety was negatively
      correlated with children's internalization and somatic symptoms. Parental anxiety
      accounted for the greatest variance in child adjustment. IMPLICATIONS FOR NURSING
      PRACTICE: These study findings may provide nurses with a better understanding of
      the vulnerability of children who have a parent with cancer and can build a
      foundation for the development of supportive interventions for these children.

PMID- 9159782
TI  - Spiritual well-being, religiosity, hope, depression, and other mood states in
      elderly people coping with cancer.
AB  - PURPOSE/OBJECTIVES: To determine the relationships among spiritual well-being,
      religiosity, hope, depression, and other mood states in elderly people coping
      with cancer and if differences in hope, depression, and other mood states exist
      between those elderly with high and low intrinsic religiosity and spiritual well
      being. DESIGN: Descriptive correlational and descriptive comparison. SETTING:
      Acute care units of two hospitals located in the midwestern United States.
      SAMPLE: 100 elderly people with diagnosis of cancer and a mean age of 73 years.
      Thirty-three of the subjects were male, and 67 were female. Sixty-two percent had
      either lung, breast, or colon cancer. METHODS: Each subject was administered an
      intrinsic and extrinsic religiosity index, a spiritual well-being scale, a
      geriatric depression scale, the Miller hope scale, and the Profile of Mood States
      scale. MAIN RESEARCH VARIABLES: Spiritual well-being, religiosity, hope,
      depression, and mood. FINDINGS: A consistent positive correlation was found among
      intrinsic religiosity, spiritual well-being, hope, and other positive mood
      states. A consistent negative correlation among intrinsic religiosity,
      depression, and other negative mood states existed. Analysis of variance
      indicated that significantly higher levels of hope and positive moods existed in
      elderly patients with high levels of intrinsic religiosity and spiritual well
      being. CONCLUSION: Intrinsic religiosity and spiritual well-being are associated
      with hope and positive mood states in elderly people coping with cancer.
      IMPLICATIONS FOR NURSING PRACTICE: Nurses must assess and support intrinsic
      religiosity and promote spiritual well-being in elderly people coping with
      cancer.

PMID- 9159783
TI  - Managing bowel elimination problems in patients with cancer.
AB  - PURPOSE/OBJECTIVES: To provide strategies for the assessment and management of
      bowel elimination disorders and to standardize approaches to prevent bowel
      disorders. DATA SOURCES: Articles, books, ongoing clinical research. DATA
      SYNTHESIS: The type and degree of bowel elimination problems vary with the type
      of tumor and treatment received. Prediction of potential bowel problems based on
      treatment given dictates a bowel management program to prevent problems and help
      patients deal with the outcome of the treatment. A standard care plan that
      includes assessment and intervention for various bowel elimination problems
      provides specific guidelines for nursing care. CONCLUSIONS: Bowel function in the
      patient with cancer inevitably will be affected while going through treatment or
      as the disease progresses. IMPLICATIONS FOR NURSING PRACTICE: Nursing care to
      relieve these problems can significantly affect the patient's quality of life. As
      patients are diagnosed with cancer and undergo cancer therapy, they can hope for
      bowel management through nursing guidance and patient education.

PMID- 9159784
TI  - Exploring the everyday world of the patient in isolation.
AB  - PURPOSE/OBJECTIVES: To explore the phenomenon of isolation from the perspective
      of patients cared for in reverse isolation for bone marrow transplant (BMT).
      DESIGN: Interpretive, phenomenologic. SETTING: Hematology and bone marrow
      transplant unit of a large teaching hospital in Brisbane, Australia. SAMPLE:
      Seven patients undergoing BMT. METHODS: Phenomenologic interviews and thematic
      analysis of transcribed data. MAIN RESEARCH VARIABLE: Patient's day-to-day
      experiences of reverse isolation. FINDINGS: Although appreciative of the physical
      care and attention given to them, participants did not convey a sense that
      healthcare professionals understood the experience of the BMT recipient's
      isolation or illness from their perspective. Major themes elicited from analysis
      of the transcripts included (a) striving to take charge, which refers to
      participants' attempts to maintain control in a seemingly out-of-control
      situation. (b) intellectualizing the need for isolation, and (c) being in touch:
      contact with family and staff. CONCLUSIONS: Elements of caring for the patient
      appeared to dominate the comments associated with staff contact. Other forms of
      care (e.g., caring about) emphasize the importance of nurses understanding and
      connecting with peoples' meanings and experiences of their illness and treatment.
      IMPLICATIONS FOR NURSING PRACTICE: Although all participants were aware that they
      could ask for information about their diagnosis and treatment at any time, most
      had not been offered the opportunity to describe their feelings or experiences
      before. Unless nurses take more initiative to gain insight and a greater
      appreciation of the patient's understanding of his or her situation, they will
      continue to focus on unidimensional aspects of care and neglect the
      multidimensional or holistic nature of nursing care.

PMID- 9159785
TI  - Genetic predisposition testing: clinical implications for oncology nurses.
AB  - PURPOSE/OBJECTIVES: To describe for oncology nurses the clinical implications of
      genetic predisposition testing for alterations in cancer susceptibility genes.
      DATA SOURCES: Published research and educational manuscripts, books, conference
      proceedings, and personal experiences. DATA SYNTHESIS: Genetic predisposition
      testing for inherited cancer risk has profound clinical implications that
      eventually will affect all areas of nursing practice. The provision of genetic
      information raises issues about cancer risk management, psychosocial sequelae,
      and legal and professional liability. CONCLUSION: Most healthcare professionals,
      including nurses, are not adequately prepared to manage the issues resulting from
      genetic predisposition testing. Furthermore, little data are available to guide
      practice. Unique educational strategies are needed to prepare providers in this
      practice arena. IMPLICATIONS FOR NURSING PRACTICE: Genetic predisposition testing
      is becoming more common in general oncology and primary care communities. Nurses
      will play a major role in the support, counseling, education, informed consent,
      and follow-up care of individuals who are considering undergoing or who have
      undergone testing. To meet the needs of patients and their families, oncology
      nurses must prepare themselves for this new area of practice.

PMID- 9159786
TI  - Chemoprevention of cancer: review of the literature.
AB  - PURPOSE/OBJECTIVES: To explain the concept of cancer chemoprevention, describe
      chemoprevention trials, and discuss the agents currently under study to lower the
      incidence of oral premalignancy and head and neck, lung, breast, prostate, and
      colon cancers. DATA SOURCES: Published journal articles, books, bulletins,
      monographs, protocols, and professional experience. DATA SYNTHESIS:
      Chemoprevention is a promising approach to cancer control, and several key agents
      have been identified that may be able to block carcinogenesis. Phase III
      chemoprevention trials are being conducted to identify the role of agents (e.g.,
      retinoids, tamoxifen, finasteride, aspirin) in cancer prevention. CONCLUSION:
      Knowledge of the genetic and hormonal changes that occur during carcinogenesis
      continues to increase. Agents are being identified that block the development of
      cancer by arresting carcinogenesis. As more agents are identified and
      investigated, their importance in chemoprevention is increasing. IMPLICATION FOR
      NURSING PRACTICE: The goal of nursing care for participants in prevention trials
      is to promote compliance with the study protocol while supporting optimum quality
      of life. Through proactive education of participants, family members, and the
      public and skillful management of side effects, nurses can play an integral part
      in the success of prevention trials.

PMID- 9159787
TI  - Emerging strategies in the management of cancer.
AB  - PURPOSE/OBJECTIVES: To review advances in understanding the biology of cancer
      that will lead to new prognostic indicators and approaches for treating cancer
      and its metastases and to explore the implications of these developments for
      oncology nurses. DATA SOURCES: Published papers, abstracts, research result,
      package inserts, books, and personal experience. DATA SYNTHESIS: Understanding is
      evolving that cancer is a genetic disease that occurs when a single cell and its
      progeny are remarkably changed by a series of genetic mutations. A new paradigm
      for managing cancer is emerging that is based on new prognostic indicators,
      intracellular and intercellular communication, and biologic control. Potential
      new therapeutic strategies include gene-directed therapy, control of cellular
      proliferation, exploitation of cell death, inhibition of metastasis, and reversal
      of multidrug resistance. Many of these therapies are only beginning to enter
      phase I/II clinical trials. CONCLUSIONS: With continued progress, doctors will be
      able to identify patients with the highest likelihood of experiencing recurrent
      or progressive disease and formulate therapeutic strategies specific for their
      disease and even for their individual genetic makeup. IMPLICATIONS FOR NURSING
      PRACTICE: To remain abreast of these new and increasingly sophisticated
      treatments, oncology nurses must be knowledgeable about cell and cancer biology,
      human genetics, the immune system, a how advances in these fields are forming the
      foundation for new therapies. Nurses with creativity and drive will continue to
      lead the way in developing management strategies for patients receiving these new
      therapies.

PMID- 9159788
TI  - Prostate cancer and African-American men.
AB  - Mortality from prostate cancer is two to three times greater among African
      American men between the ages of 50 and 70 than among American Caucasian men of
      similar ages. Also, African-Americans tend to present with more advanced tumors
      than their American Caucasian counterparts. This article explores differences
      between the two races that may account for the disproportionately high mortality
      among African-Americans and their more advanced disease stage at presentation.
      These include epidemiologic and histologic features of prostate cancer; clinical,
      biologic, and environmental factors; and barriers to health care. Various
      important issues that warrant further investigation are also highlighted.

PMID- 9159789
TI  - More on the treatment of anal margin carcinomas.

PMID- 9159790
TI  - Management of tumors of the parapharyngeal space.
AB  - Benign and malignant tumors can arise from any of the structures contained within
      the parapharyngeal space. Such tumors are very rare, however. Also, malignant
      tumors from adjacent areas (eg, the pharynx) can extend into the parapharyngeal
      space by direct growth, or distant tumors may metastasize to the lymphatics
      within the space. Although the history and physical examination can provide clues
      to the site of origin and nature of a parapharyngeal space tumor, imaging studies
      are more useful for defining the site of origin and extent of the mass, as well
      as its vascularity and relationship to the great vessels of the neck and other
      neurovascular structures. Surgery is the mainstay of treatment. The surgical
      approach chosen should facilitate complete tumor extirpation with minimal
      morbidity. Irradiation is administered as primary therapy in patients with
      unresectable tumors, poor surgical candidates, and selected other patients.
      Radiation therapy is also used after surgery for high-grade malignancies or when
      wide surgical margins cannot be achieved.

PMID- 9159791
TI  - Clinical Trials. Referral resource Clinical trials using CI-980 (mivobulin
      isethionate).

PMID- 9159792
TI  - Speech and swallowing rehabilitation for head and neck cancer patients.
AB  - Head and neck cancer and its treatment frequently cause changes in both speech
      and swallowing, which affect the patient's quality of life and ability to
      function in society. The exact nature and severity of the post-treatment changes
      depend on the location of the tumor, the choice of treatment, and the
      availability and use of speech and swallowing therapy during the first 3 months
      after treatment. This paper reviews the literature on speech and swallowing
      problems in various types of treated head and neck cancer patients. Effective
      swallowing rehabilitation depends on the inclusion of a video-fluorographic
      assessment of the patient's oropharyngeal swallow in the post-treatment
      evaluation. Pilot data support the use of range of motion (ROM) exercises for the
      jaw, tongue, lips, and larynx in the first 3 months after oral or oropharyngeal
      ablative surgical procedures, as patients who perform ROM exercises on a regular
      basis exhibit significantly greater improvement in global measures of both speech
      and swallowing, as compared with patients who do not do these exercises.

PMID- 9159793
TI  - Summary of the NIH Consensus Development Conference on Cervical Cancer.

PMID- 9159794
TI  - Key molecule found to prolong survival of HIV patients.

PMID- 9159795
TI  - Radiation therapy for malignancies in the setting of HIV disease.
AB  - With the introduction of increasingly effective antiretroviral agents for the
      management of AIDS, the life expectancy of appropriately treated patients will
      continue to lengthen as will the length of time during which infected patients
      amy develop malignancies, both HIV-related and non-HIV-related. The management of
      such patients will require careful consideration of the impact of all oncologic
      therapy on the immune system's ability to hold the virus at bay. Radiation
      therapy, with its recognized immunosuppressive effects, plays an important role
      in the management of the major AIDS-defining neoplasms, Kaposi's sarcoma, primary
      central nervous system lymphoma, and cervical carcinoma, and is used in
      approximately 50% of patients with non-HIV-related malignancies at some point in
      the disease course. The judicious use of radiation therapy and proper integration
      of aggressive antiretroviral therapy can result in control of malignancies
      without contributing to the rapid progression of HIV disease.

PMID- 9159796
TI  - Current role of retroperitoneal lymph node dissection in testicular cancer.
AB  - Carcinoma of the testis is the most common malignancy in males 15 to 35 years of
      age. Testicular cancer has become one of the most curable solid neoplasms and as
      such, serves a paradigm for the multimodality treatment of malignancies. The cure
      rate for patients with clinical stage I disease is nearly 100%, and patients with
      advanced disease now achieve complete remission rates of over 90%. The markedly
      improved outlook for patients with this cancer over the past 15 years has led to
      a reassessment of management options, especially in patients with clinical stage
      I disease. The realization that platinum-based chemotherapy could cure most
      patients with an advanced nonseminomatous germ cell tumor (NSGCT), especially
      those with minimal disease, led to the introduction of various strategies to
      decrease the morbidity associated with surgical management. These strategies
      include surveillance protocols, chemotherapy for clinical stage II disease, and
      observation protocols for a subset of patients with advanced disease who have had
      a partial response to chemotherapy. Retroperitoneal lymph node dissection (RPLND)
      has an important place in the management of both low- and high-stage testicular
      cancer. It offers the patient two basic benefits: accurate staging and the
      possibility of a surgical care, even in the presence of metastatic disease.

PMID- 9159797
TI  - Role for androgen withdrawal prior to radiation and surgery for prostate cancer?

PMID- 9159798
TI  - Viramune, new antiretroviral agent, crosses the blood-brain barrier.

PMID- 9159799
TI  - Evaluating research--a not-so-great British experience.

PMID- 9159800
TI  - Effect of VDUs on the eyes.

PMID- 9159801
TI  - Bilateral disc edema in retinitis pigmentosa.
AB  - Retinitis pigmentosa (RP), one of the most common forms of hereditary retinal
      degeneration, is characterized by night blindness and constricted visual fields.
      In addition to bone spicule pigmentation, other ocular findings may include
      posterior subcapsular cataracts, cystoid macular edema, and hyaline bodies or
      drusen of the optic nerve. Rarely, optic nerve head (ONH) edema has been reported
      to be associated with RP. A 44-year-old white male with RP and neurosensory
      hearing loss (Usher's syndrome type II) presented to our clinic for routine
      examination. A dilated fundus examination revealed bone spicule pigmentation,
      vessel attenuation, several flame hemorrhages on or adjacent to the nerves, and
      ONH edema in the right eye. B-scan ultrasonography revealed drusen of the right
      ONH but not of the left. Late stage fluorescein angiography showed
      hyperfluorescence and dye leakage from both optic discs which was more pronounced
      in the right eye than the left. Computed tomography (CT) of the head and orbits
      and cerebrospinal fluid (CSF) examination by lumbar puncture were normal. The
      differential diagnosis of bilateral ONH edema in this case included ONH drusen or
      papilledema secondary to increased intracranial pressure. This patient was found
      to have RP with asymmetric, bilateral ONH edema of unknown cause. One theory
      regarding the cause of the ONH edema is disc vessel leakage secondary to an
      inflammatory reaction caused by rapid photoreceptor and retinal pigment
      epithelium (RPE) degeneration.

PMID- 9159802
TI  - An optical intervention for visual hallucinations associated with visual
      impairment in an elderly patient.
AB  - A case study of a 100-year-old patient with visual hallucinations and visual
      impairment is presented. The patient was fit with optical aids in an effort to
      reduce the hallucinations, operating on the "phantom vision" theory, which
      postulates that visual hallucinations associated with visual impairment result
      from the brain's attempt to "fill in" for compromised visual input.

PMID- 9159803
TI  - Babe Ruth: with vision like that, how could he hit the ball?
AB  - Unfortunately, it is unlikely that a definitive answer will be known. We believe
      that it is most likely that Ruth was not amblyopic. This seems possible only if
      Dr. Kara had missed some amblyogenic factor such as strabismus or a significant
      refractive error. Our favored solution is that Ruth's unilateral vision loss was
      a complication of his cancer, and that Dr. Kara's examination occurred before the
      optic nerve damage became detectable. Of course, this is in disagreement with the
      ophthalmologist who examined his eyes.

PMID- 9159804
TI  - Keratoconus: age of onset and natural history.
AB  - Keratoconus is a corneal dystrophy that degrades the optical function of the
      cornea. The onset of the process manifests optical signs: evolving astigmatism,
      failure of optical correction by spectacles, and distorted images. We report data
      from 74 keratoconus patients in need of keratoplasty. The variables studied
      included sex, age of onset, and refractive error. We find that the average age of
      the appearance of keratoconus is the second decade of life (mean age of onset =
      15.39 years, SD = 3.95), with earlier onset occurring in females that in males,
      although the differences are not statistically significant. The mean corneal
      astigmatism before keratoplasty was 4.07 D (SD = 1.57). Optometrists should refer
      patients for surgery when all optical treatment has failed.

PMID- 9159805
TI  - Relative effects of aging and age-related macular degeneration on peripheral
      visual function.
AB  - The purpose of this study was to determine the extent of peripheral visual
      deficits in patients with early age-related macular degeneration (ARMD) using
      electrophysiological and psychophysical techniques. Dark-adaptation curves,
      electro-oculograms (EOGs), and electroretinograms (ERGs) were obtained from
      patients with early ARMD and from normally sighted control subjects. The control
      subjects' data were used to calculate age-dependent 95% confidence intervals for
      each measure of visual function. For the control subjects, performance on all our
      measures of visual function decreased with age. For the patients with early ARMD,
      the cone system absolute thresholds, EOG ratios, and cone-dominated ERG
      amplitudes and implicit times were within the range of normal age-related
      changes. Rod system absolute thresholds, cone-rod break times, and rod-dominated
      electroretinographic measures were abnormal in some patients. These results
      suggest that when the effects of aging are taken into account, some patients
      classified as early ARMD may not show significant changes in peripheral retinal
      function with standard clinical tests.

PMID- 9159806
TI  - Efficacy of a mydriatic spray in the pediatric population.
AB  - BACKGROUND: Children often resist instillation of mydriatic drops for dilated
      fundus evaluation. As cycloplegic sprays have proven useful, this study's aim was
      to demonstrate efficacy of a mydriatic spray. METHODS: Twenty-two healthy
      subjects, ages 2 to 8 years, participated in the study. All but two had dark
      brown irides. Subjects were given either one drop each of 1% tropicamide and 2.5%
      phenylephrine in each eye or one application of mydriatic spray (containing
      concentrations of 0.5% tropicamide and 2.5% phenylephrine) to each closed eyelid.
      Pupils were measured with a pupil gauge before drug delivery and every 10 min
      thereafter, for 40 min. RESULTS: Repeated measures analysis of variance for the
      five time intervals demonstrated no significant difference between the two
      application methods nor in the method/time interaction, but a statistically
      significant increase in pupil size over time (p < 0.0005) for each method. A t
      test revealed no statistically significant difference in pupil size (p > 0.05)
      between the two methods of drug administration at 40 min after application.
      CONCLUSIONS: This study suggests that use of mydriatic sprays on closed eyelids
      is as efficacious as use of mydriatic drops in open eyes for children.

PMID- 9159808
TI  - Guidelines for radiologic examinations: do we have all the answers yet?

PMID- 9159807
TI  - Structural damage to Schiotz tonometers after disinfection with solutions.
AB  - Although Schiotz tonometry has been long ago replaced by Goldmann applanation
      tonometry measurement of intraocular pressure, it remains a viable clinical
      technique in nursing homes and other "out of office" settings. Because Schiotz
      tonometers come into contact with the cornea and tear film, they must be properly
      disinfected to prevent cross-infection with HIV and other infectious pathogens.
      The Centers for Disease Control and Prevention (CDC) recommends that all eye
      contact devices be disinfected by a 5- to 10-min soak in one of following
      disinfectants: 3% hydrogen peroxide, 1:10 sodium hypochlorite (household bleach),
      or 70% isopropyl alcohol. The effects of these disinfectants on Schiotz
      tonometers have not been previously investigated. This study investigated the
      effects of CDC-recommended disinfectants on the structural integrity of Schiotz
      tonometers. The results of the study indicated that soaking in 1:10 sodium
      hypochlorite and 3% hydrogen peroxide damaged Schiotz tonometers and rendered
      them inoperable. Alcohol caused minor damage to the tonometer and was the safest
      of the CDC disinfectants. This study showed there is limited application of CDC
      infection control criteria to Schiotz tonometers due to the extensive corrosion
      and damage caused by hydrogen peroxide and bleach.

PMID- 9159809
TI  - The medically compromised patient (MCP): how should undergraduates be trained?

PMID- 9159810
TI  - Buccal mass with ulceration.

PMID- 9159811
TI  - Postoperative stability after sagittal split ramus osteotomy with condylar
      positioning appliance and screw fixation: asymmetric versus symmetric cases.
AB  - OBJECTIVE: The purpose of this study was to evaluate postoperative stability in
      prognathic patients with mandibular asymmetry who were treated with sagittal
      split ramus osteotomy of the mandible. STUDY DESIGN: Ten asymmetric (group I) and
      11 symmetric (group II) patients were examined. An appliance for repositioning
      the proximal segment was applied, and the bony segments were fixed with titanium
      screws. Cephalograms were obtained preoperatively, 2 to 3 days postoperatively,
      and 3 and 6 months after surgery. Changes in the positions of the standard points
      were examined on lateral cephalograms, and changes in the widths of the gonion
      points were examined on posteroanterior cephalograms. RESULTS: Statistical
      analysis revealed no significant difference between the two groups. In addition,
      there was no significant difference between the postoperative changes in the
      widths of the gonion points on the deviated and nondeviated sides in group I.
      CONCLUSIONS: This study suggests that application of an appliance for
      repositioning the proximal segment can minimize postoperative skeletal changes in
      patients with asymmetry.

PMID- 9159812
TI  - The utility of toluidine blue application as a diagnostic aid in patients
      previously treated for upper oropharyngeal carcinoma.
AB  - OBJECTIVES: This study evaluated the utility (usefulness) of toluidine blue
      application as an aid to the recognition and diagnosis of clinically evident
      lesions in a series of patients previously treated for oral cancer and monitored
      in a cancer center. In addition to increased risk of recurrence of cancer or new
      second primary lesions, patients who have had previous treatment for
      oropharyngeal cancer may be more difficult to assess because of tissue changes
      that occur as a result of previous radiation therapy. STUDY DESIGN: Patients with
      a history of oral malignancy were assessed by clinical examination followed by
      application of toluidine blue. Biopsy sites were determined on the basis of
      unaided visual examination and by the findings on toluidine blue application.
      Biopsy specimens were reviewed by a pathologist blinded to the clinical findings.
      RESULTS: Unaided clinical examination identified 78% of carcinoma in situ or
      invasive malignant lesions compared with toluidine blue application, which
      identified all (100%) carcinoma in situ or invasive malignant lesions (p = 0.02)
      and produced no false-negative findings. No differences were found between
      clinical examination and toluidine application in the detection of dysplastic
      lesions. CONCLUSION: Toluidine blue retention was seen in all cases of carcinoma
      in situ and invasive carcinoma, and no false-negative findings were seen with
      toluidine blue. When used by a trained and experienced clinician in a cancer
      center, toluidine blue was a valuable visual aid to clinical examination of oral
      mucosal lesions.

PMID- 9159813
TI  - Growth potential of peripheral giant cell granuloma.
AB  - PURPOSE: The purpose of this study was to investigate the association of selected
      demographic, systemic health, and oral health characteristics of patients with
      large (> 2 cm) peripheral giant cell granuloma and to assess its growth potential
      and the possible underlying causes. METHODS: A series of 79 cases including 15
      subjects with lesions 2 to 5 cm in the largest diameter is presented. Age, sex,
      site, size, systemic health, oral hygiene, and report of oral dryness of subjects
      with large lesions were compared with those of subjects with small lesions (< 2
      cm). RESULTS: No differences were found in mean age between the small lesion
      group (mean age = 31 +/- 6 years) and the large lesion group (mean age 53 +/-
      24.2 years). Female predilection (male/female ratio 1:1.5, 1:2.75.) was more
      significant in patients with large lesions. No statistically significant
      differences were found in systemic health score (mean American Society of
      Anesthesiology score 1.39, 1.53). Oral hygiene score (percent calculus 78% +/-
      3.1%, 95% +/- 2.7%, percent gingival bleeding 58% +/- 3.6%, 73% +/- 5.4%, percent
      deep pocket 30% +/- 2.8%, 42% +/- 3.1) was better among the patients with small
      lesions. The percentage of patients with a report of oral dryness was
      significantly higher (3.1%, 27%) among patients with large lesions. CONCLUSIONS:
      Findings from this study suggest that patients with large (> 2 cm) peripheral
      giant cell granuloma lesions are more likely to be women with lower oral hygiene
      scores and xerostomia. Further studies are required to measure the relative risk
      of these factors.

PMID- 9159814
TI  - Bilateral parotid sialolithiasis in a patient with acquired immunodeficiency
      syndrome and immunoglobulin G multiple myeloma.
AB  - Bilateral multiple parotid calculi, which are uncommonly diagnosed in the normal
      population, have never been reported in patients infected with human
      immunodeficiency virus. Herein we report a case of bilateral parotid
      sialolithiasis in a patient who had acquired immunodeficiency syndrome and was
      affected by multiple myeloma. The possible etiopathogenesis in view of the
      alterations of immunity, oral pH, and salivary composition that are observed in
      multiple myeloma and in human immunodeficiency virus infection are discussed.

PMID- 9159816
TI  - Foreign body gingivitis: clinical and microscopic features of 61 cases.
AB  - Gingival inflammation associated with foreign bodies in connective tissue is
      termed foreign body gingivitis. It is not recognized commonly by clinicians and
      has not been described fully in the literature. This study examined the clinical
      and microscopic features of 61 cases of foreign body gingivitis. It was more
      common in women and occurred at a mean age of 48 years. It presented most
      frequently as a red or red and white painful chronic lesion that had been present
      for less than 1 year. Often it was diagnosed clinically as lichen planus. There
      was no gingival site predilection. Microscopically, foreign bodies, usually less
      than 5 microns in diameter, were found in an area of moderate to severe
      inflammation composed of lymphocytes, histiocytes, and plasma cells. The
      inflammation frequently was granulomatous and sometimes lichenoid.

PMID- 9159815
TI  - Numb chin syndrome as an initial symptom of acute lymphocytic leukemia: report of
      three cases.
AB  - This article describes three cases of acute lymphocytic leukemia that presented
      with mental neuropathy, or so-called "numb chin syndrome," as the initial symptom
      of the disease. This symptom heralded the initial progression of the disease in
      the first and second cases and the recurrence of the disease in the third case.
      In these cases tenderness in the mental foramen, percussion pain of the teeth,
      loosening and extrusion of the teeth, and radiographic abnormalities were also,
      if not always, observed in association with mental neuropathy. The radiographic
      abnormalities included a disappearance of the mandibular canals, an enlarged
      periodontal ligament space, a loss or thinning of the lamina dura, and a
      destruction of the alveolar crestal bone. This report indicates that oral
      manifestations can therefore occasionally play an extremely important role in the
      early recognition of acute lymphocytic leukemia. The unexplained oral
      abnormalities such as numbness of the chin and lower lip must thus be considered,
      potentially ominous indication of acute lymphocytic leukemia.

PMID- 9159817
TI  - Foreign body gingivitis: identification of the foreign material by energy
      dispersive x-ray microanalysis.
AB  - Foreign bodies identified in 61 cases of foreign body gingivitis were analyzed by
      energy-dispersive x-ray microanalysis. This was compared with the energy
      dispersive x-ray microanalysis of 62 dental materials. Comparative analysis
      indicated most foreign bodies were of dental material origin, usually abrasives.
      It is suggested that they are factitially and iatrogenically introduced during a
      variety of self-administered and professionally performed dental hygiene and
      restorative procedures. Individual elements, and elements by class, were
      correlated with previously described clinical and microscopic features of the
      cases. There was no association between any microscopic or clinical attribute of
      FBG and the presence of allergenic or cytotoxic elements. It is postulated that
      the physical presence of foreign bodies may be sufficient for the development of
      foreign body gingivitis. Dentists should be aware of the potential for chronic
      tissue damage that can result from the unguarded use of abrasive material next to
      the gingiva.

PMID- 9159818
TI  - Extraosseous calcifying epithelial odontogenic tumor: report of two cases and
      review of the literature.
AB  - In this study two additional cases of extraosseous calcifying epithelial
      odontogenic tumor are reported, both of which exhibited a prominent clear cell
      component. The clinical and histopathologic findings of these two cases are
      compared with those of the nine reported cases from the English language
      literature. The age range for the 11 cases was 12 to 64 years with a mean age of
      34.4 years at the time of diagnosis. Six of the tumors involved female patients
      and five involved male patients. Seven cases were located on the mandibular
      gingiva with the remaining four cases involving the maxillary gingiva. On
      microscopic evaluation, six of the lesions exhibited a predominant clear cell
      component. Appropriate management of the extraosseous calcifying epithelial
      odontogenic tumor consists of simple excision. No recurrences have been recorded.

PMID- 9159819
TI  - Basaloid squamous cell carcinoma of the esophagus metastatic to the gingiva: a
      case report.
AB  - Basaloid squamous cell carcinoma (BSCC), a biologically high-grade variant of
      squamous cell carcinoma, carries a grave prognosis. In this article, we describe
      a rare case of BSCC of the esophagus with metastasis to the mandibular gingiva in
      a 63-year-old man. In addition, we provide a review of the relevant literature
      along with a discussion of the differential diagnosis.

PMID- 9159820
TI  - Comparison of integrin alpha chain expression in benign and malignant salivary
      gland tumors.
AB  - OBJECTIVE: This study investigates the distribution of the alpha chain of the
      integrin family of extracellular matrix receptors in a series of adenomas and
      carcinomas of salivary gland origin to determine if the malignant phenotype is
      associated with modification of the expression of these receptors. STUDY DESIGN:
      Cryostat sections of 36 tumor specimens were stained by a standard streptavidin
      biotin-peroxidase technique using primary monoclonal antibodies against alpha 1-6
      and alpha v integrin chains. The immunohistochemical reaction was scored using a
      three-point scale and the results were analyzed using Fisher's exact test.
      RESULTS: In salivary adenomas, alpha 2, alpha 3, alpha 4, alpha 6, and alpha v
      chains were widely expressed in most of the cases studied. The alpha 1 subunit
      was prominently expressed by the epithelial cells of Warthin's tumor, whereas a
      minority of pleomorphic adenomas showed immunoreactivity for this antigen. We
      observed alpha 5 subunit expression only in the mesenchymal-like component of
      pleomorphic adenomas. In salivary carcinomas, integrin alpha chain expression was
      heterogeneous, varying greatly between different histotypes and within the same
      histotype. The distribution of the antigens was similar to that of adenomas,
      except for the alpha 6 chain, which localized not only at the interface between
      cell and matrix, but also at sites of cell-cell contact. When the
      immunohistochemical levels of integrin alpha chain expression were compared in
      adenomas and carcinomas, expression significantly decreased for the alpha 6 and
      alpha v chains (p = 0.0007; p = 0.002, respectively). CONCLUSIONS: Loss of alpha
      6 and alpha v integrin subunits occurring in salivary gland carcinomas could
      modify the adhesive properties of malignant cells, contributing to the invasive
      potential of these tumors.

PMID- 9159821
TI  - Relationship between apical and marginal healing in periradicular surgery.
AB  - OBJECTIVE: The purpose of the present study was to evaluate the relationship
      between apical and marginal periodontal healing after periapical surgery. STUDY
      DESIGN: The investigation was conducted on 59 patients referred for periradicular
      surgery. A radiographic examination as well as assessments of periodontal
      attachment and pocket depth of teeth undergoing surgery and control teeth were
      performed at the time of surgery and 1 year after surgery. The radiographic
      periapical healing pattern was evaluated. RESULTS: After an observation time of 1
      year, 85% of the healing patterns were classified as successful or uncertain.
      Teeth within the surgical area showed a significant loss of clinical attachment
      during the observation period. The mean clinical attachment loss in teeth with an
      unsuccessful healing was 0.85 mm and differed significantly from successfully
      healed cases (mean, 0.15 mm). CONCLUSIONS: A persisting endodontic infection may
      be regarded as a contributing risk factor for a progressing marginal attachment
      loss.

PMID- 9159822
TI  - Comparison of the intraosseous biocompatibility of Vitremer and super EBA by
      implantation into the mandible of rabbits.
AB  - OBJECTIVES: This study compared the intraosseous biocompatibility of Vitremer, a
      new hydrophilic glass-ionomer cement, to that of Super EBA. STUDY DESIGN: Twenty
      two New Zealand rabbits were anesthetized, the mandibular bone exposed, and two
      holes were drilled through the cortical plate. The materials were loaded into
      silicone carriers and inserted into the mandibles. Eleven rabbits were killed 4
      weeks after implantation, 11 animals after 12 weeks. The mandibles were prepared
      with standard histologic procedures; the tissue reactions were graded from none
      to very severe. RESULTS: At 4 weeks Vitremer implants showed very slight to
      slight reactions, and the Super EBA implants showed slight reactions and one
      moderate reaction with no significant difference between the two materials. At 12
      weeks, bone healing had occurred, despite the persistence of some fibrous tissue
      interposition. The reactions were classified as none to very slight for Vitremer
      and very slight to slight for EBA. Statistical analysis showed better results for
      Vitremer at 12 weeks. CONCLUSION: The intraosseous biocompatibility of Vitremer
      was similar at 4 weeks and superior at 12 weeks to that of Super EBA. Its other
      properties should be evaluated before considering its use in clinical practice.

PMID- 9159823
TI  - Imaging of the temporomandibular joint: a position paper of the American Academy
      of Oral and Maxillofacial Radiology.
AB  - Various imaging techniques for the temporomandibular joint are discussed with
      respect to uses, strengths, and limitations. An imaging protocol is outlined for
      evaluating patients with a wide variety of temporomandibular joint related signs
      and symptoms.

PMID- 9159824
TI  - An analysis of the scientific basis for the radiographic guideline for new
      edentulous patients.
AB  - The FDA Radiology Guideline for the new edentulous patient recommends an initial
      survey of the arches. In the process of developing this recommendation, the
      expert panel reviewed the available literature and concluded that there was
      sufficient evidence to warrant screening radiography rather than selective
      radiography, which is the principle on which all the other recommendations are
      based. Our evaluation of the literature used by the panel for the edentulous
      recommendation identifies critical errors in the analysis of the data. Factors
      such as a vague definition of abnormality and a geographically diverse sample
      population might have led the expert panel to suggest a very conservative
      recommendation for this group of patients. The recommendation failed to consider
      the treatment impact of findings and was based simply on the large number of
      observations, regardless of their treatment or pathologic significance. However,
      in studies in which treatment is considered, it is clear that screening
      radiography for new edentulous patients does not yield sufficient clinically
      relevant information to support the guideline.

PMID- 9159825
TI  - Radiographic guidelines for edentulous patients.

PMID- 9159826
TI  - Longitudinal radiographic assessment of dense bone islands of the jaws.
AB  - OBJECTIVES: This study assessed dense bone island (DBI) inception and growth in
      jaws. STUDY DESIGN: A population of 2991 patients (age range 5 to 35 years) was
      studied with at least two panoramic radiographs taken 1 to 10 years apart for
      each patient. Lesions were digitized and measured with computer measuring
      software. The size of the earliest DBI was compared with subsequent DBI
      measurements after the latter measurement was normalized with reference to the
      size of the nearest tooth. RESULTS: Sixty-nine patients with DBIs were
      identified. A total of 3.1% of the patients with DBI were found in the 5- to 10
      year age range, with the first patient in the DBI group found at 9.4 years. A
      significantly higher proportion (p = 0.002) of the unaffected patients (26%) was
      found in the same 5-to 10-year age range. The proportions of patients in the DBI
      and unaffected groups in older age ranges were similar. Assessment of DBI size
      changes showed that 43% of the 53 DBIs detected between 9.4 and 19 years enlarged
      (mean change, 212%), and 17% diminished (mean change, 49%). In comparison, 29.4%
      of 17 DBIs detected between 20 and 35 years enlarged (mean change, 153%), and
      5.9% diminished (mean change, 60%). CONCLUSION: Our results indicate that DBIs
      are labile lesions, develop during early adolescence, and retain a potential for
      enlargement, or to a lesser extent shrinkage, into adulthood.

PMID- 9159827
TI  - Evidence-based practice of peritoneal dialysis.

PMID- 9159828
TI  - Commentary: cardiomyopathy of anemia and the potential of erythropoietin.

PMID- 9159829
TI  - What is "adequate" peritoneal dialysis in children?

PMID- 9159830
TI  - Role of imbalance of intracavity fibrin formation and removal in the pathogenesis
      of peritoneal lesions in CAPD.

PMID- 9159831
TI  - How to measure ultrafiltration failure: 2.27% or 3.86% glucose?

PMID- 9159832
TI  - Erythropoietin treatment decreases cardiovascular morbidity and mortality in CAPD
      patients.
AB  - OBJECTIVE: To analyze the effects of recombinant human erythropoietin (rHuEPO)
      therapy on cardiovascular (CV) morbidity and mortality among continuous
      ambulatory peritoneal dialysis (CAPD) patients. DESIGN: Retrospective comparative
      study. SETTING: CAPD unit in a university hospital. PATIENTS: Forty-two patients
      on rHuEPO treatment for at least one year were compared with an rHuEPO nonuser
      group of 113 patients. Subcutaneous rHuEPO doses were adjusted to a hemoglobin
      objective level of 10.5-13.5 g/dL. Fifty-seven patients were considered as high
      cardiovascular risk (HCVR), 17 in the rHuEPO group and 40 in the rHuEPO nonuser
      group. Ninety-eight patients were classified as low cardiovascular risk (LCVR),
      25 of whom were in the rHuEPO group. RESULTS: The incidence of cardiovascular
      morbidity was more frequent in the rHuEPO nonuser than in the rHuEPO user group
      (40% vs 22%) and in HCVR than in LCVR patients (59.6% vs 20.4%). By multiple
      logistic regression analysis, the best model to explain the development of
      cardiovascular morbidity comprises rHuEPO treatment, CV risk, and age. In the
      rHuEPO user group, HCVR and LCVR patients did not show significant differences in
      survival, while in the rHuEPO nonuser group, HCVR patients had a lower survival
      rate than LCVR patients (p = 0.0003). Cox proportional hazards model revealed
      that LCVR patients had an excellent prognosis compared with HCVR patients in the
      rHuEPO nonuser group, but this difference disappeared in the rHuEPO user group.
      CONCLUSION: These data show a beneficial effect of rHuEPO treatment on
      cardiovascular morbidity and mortality in CAPD patients, evidenced by the
      elimination of the correlation between prior cardiovascular risk and subsequent
      mortality.

PMID- 9159833
TI  - Peritoneal sclerosis in chronic peritoneal dialysis patients: analysis of
      clinical presentation, risk factors, and peritoneal transport kinetics.
AB  - OBJECTIVE: To analyze clinical features of peritoneal sclerosis (PS) in a group
      of peritoneal dialysis (PD) patients, and to compare potential risk factors and
      peritoneal transport characteristics with a control group matched for duration of
      PD. DESIGN: Study 1: Retrospective study of 16 PD patients with PS. Study 2: Case
      control study comparing 10 patients with evident PS to 30 control patients who
      were matched for duration of PD. SETTING: Continuous Ambulatory Peritoneal
      Dialysis unit in the Academic Medical Centre in Amsterdam. RESULTS: The incidence
      of PS was 3.5 per 1000 patient years. PS was diagnosed either during PD (n = 10),
      in patients on hemodialysis (n = 2), or after successful transplantation (n = 4).
      Presenting symptoms were bowel obstruction, ascites, blood-stained effluent, and
      impaired net ultrafiltration. Macroscopic confirmation of the diagnosis was
      possible in 13 patients. Sclerotic encapsulation was present in 8 of them.
      Patients with PS were divided into three groups based on clinical symptoms and
      typical macroscopical findings. In category I the diagnosis PS was obvious (10
      patients), in category II the diagnosis was highly suggestive (3 patients), and
      in category III it was doubtful (3 patients). Treatment was conservative in most
      patients. Surgical treatment was only possible in four and immunosuppressive
      therapy was given in 5 patients. Peritoneal sclerosis was the direct cause of
      death in 1 patient. Five patients died during follow-up due to other causes. At
      present, 7 patients are well and 3 patients (all from category I) still have
      recurrent bowel obstruction. Compared to matched controls, no difference existed
      in peritonitis incidence, or in the percentage of patients with former renal
      transplantations. The number of patients treated with beta-blocking agents and
      the number of previous abdominal surgeries were not different. The number of
      catheter-related surgical procedures was higher in the PS patients than in the
      control group. The mass transfer area coefficient (MTAC) of creatinine was higher
      in PS patients and net ultrafiltration with 1.36% glucose was lower. The
      estimated cumulative glucose exposure until the diagnosis of PS was made was
      larger in PS patients than in their controls. This difference was already present
      in the first year of PD treatment in 8 of 10 patients. The initial values for the
      MTAC creatinine were similar in both groups. CONCLUSIONS: The presenting symptoms
      of PS were bowel obstruction, ascites, and blood-stained effluent, often in
      combination with loss of net ultrafiltration. Peritoneal sclerosis is a
      complication of long-duration PD and could also become manifest after a
      successful renal transplant. Treatment should be conservative unless
      complications require surgical intervention. Patients with PS had lower net
      ultrafiltration and higher transport rates compared to controls who were matched
      for duration of PD. Although peritonitis incidence was similar, a relation of PS
      with severe peritonitis may be present in some patients. Glucose exposure is
      likely to be an important risk factor for PS.

PMID- 9159834
TI  - Analysis of ultrafiltration failure in peritoneal dialysis patients by means of
      standard peritoneal permeability analysis.
AB  - BACKGROUND: Ultrafiltration failure (UFF) is a complication of peritoneal
      dialysis (PD) treatment that occurs especially in long-term patients. Etiological
      factors include a large effective peritoneal surface area [measured as high mass
      transfer area coefficient (MTAC) of creatinine], a high effective lymphatic
      absorption rate (ELAR), a large residual volume, or combinations. OBJECTIVE: The
      prevalence and etiology of UFF were studied and the contribution of transcellular
      water transport (TCWT) was analyzed. A new definition of UFF and guidelines for
      the analysis of its etiology were derived from the results. SETTING: Peritoneal
      dialysis unit in the Academic Medical Center in Amsterdam. DESIGN: Cross
      sectional study of standard peritoneal permeability analyses (4-hr dwells,
      dextran 70 as volume marker) with 1.36% glucose in 68 PD patients. Patients with
      negative net UF (change in intraperitoneal volume, dIPV < 0 mL) were analyzed
      further using 3.86% glucose, whenever possible. RESULTS: Among 68 patients
      (duration of PD 0.3-178 months), 39 had negative net UF with 1.36% glucose. These
      patients had greater MTAC creatinine and glucose absorption, and higher ELAR (p <
      10(-4)) than the patients with positive UF. dIPV and transcapillary UF rate
      (TCUFR) were lower (p < 10(-5)). Twenty of these patients could be studied using
      3.86% glucose. dIPV was greater than 400 mL/4 hr in this test in 12 patients,
      implying that no clinically important UFF was present. Ultrafiltration failure
      (dIPV < 400 mL) was found in 8 patients, giving a prevalence of 23%. This last
      group had been treated with PD for a longer period (p = 0.03), had higher ELAR (p
      = 0.07), but lower residual volume (p = 0.03), and lower TCUFR (p = 0.01).
      Ultrafiltration failure was associated with a high MTAC creatinine in 3 patients,
      a high ELAR in 4 patients, and a combination of factors in one. As an additional
      possible cause, TCWT was studied, using the sodium gradient in the first hour of
      the dwell, corrected for diffusion (dNA). Five patients had dNA > 5 mmol/L,
      indicating normal TCWT. The 3 patients with dNA < 5 mmol/L tended to be treated
      longer (p = 0.19) and had lower TCUFR (p = 0.04). A smaller difference was found
      between dIPV 3.86% and 1.36% (p = 0.04) compared to the dNA > 5 mmol/L group, but
      no differences were present for MTAC creatinine, ELAR, residual volume, or
      glucose absorption. CONCLUSIONS: In addition to known factors, impairment of TCWT
      can be a cause of UFF. A standardized dwell with 1.36% glucose overestimates UFF.
      Therefore, 3.86% glucose should be used for identification of patients with UFF,
      especially because it provides additional information on TCWT. Ultrafiltration
      failure can be defined as net UF < 400 mL/4 hr with 3.86% glucose during a 4-hour
      exchange.

PMID- 9159836
TI  - Fibrinogen and fibrinolytic activity in CAPD patients with atherosclerosis and
      its correlation with serum albumin.
AB  - OBJECTIVE: It has been suggested that hypoalbuminemia in dialysis patients leads
      to a hypercoagulable state, however, the relationship between serum albumin and
      fibrinogen or fibrinolytic activity has not been well-documented. The aim of this
      study was to investigate the changes of fibrinogen, tissue plasminogen activator
      (tPA), plasminogen activator inhibitor type-1 (PAI-1), and lipid levels in
      continuous ambulatory peritoneal dialysis (CAPD) patients with atherosclerosis,
      and the relationship between those factors and serum albumin. DESIGN: A cross
      sectional study. SETTING: A university hospital. PATIENTS: Twenty CAPD patients
      with atherosclerosis, 49 CAPD patients without atherosclerosis, and 33 normal
      controls were included. Presence of atherosclerosis was determined by positive
      results in a stress thallium single-photon emission computed tomography or an
      ankle brachial index less than 0.9. Coronary angiography and/or Doppler
      ultrasound of extremities were followed for the patients with positive results to
      confirm atherosclerotic cardiovascular disease. MAIN OUTCOME MEASURES: tPA and
      PAI-1 levels were determined with ELISA method, and fibrinogen with thrombin time
      method. Serum albumin and lipids were also measured. RESULTS: Serum albumin and
      HDL-cholesterol levels were significantly lower, and the ratio of total
      cholesterol/HDL was significantly higher, in CAPD patients than in normal
      controls. CAPD patients with atherosclerosis had significantly higher fibrinogen,
      tPA, and PAI-1 levels than other groups: tPA was an independent predictor of
      atherosclerotic vascular disease in CAPD patients in stepwise logistic regression
      analysis. Serum albumin level was inversely correlated with fibrinogen (r = 
      0.28; p < 0.05) in CAPD patients, but not with tPA or PAI-1 levels. PAI-1 level
      was correlated with tPA (r = 0.37; p < 0.01) and triglycerides (r = 0.32; p <
      0.05). CONCLUSIONS: Association of high levels of fibrinogen and PAI-1 with lipid
      disorders may be of importance in the development of atherosclerosis in CAPD
      patients. Hypoalbuminemia may contribute to atherosclerosis via increased
      synthesis of fibrinogen.

PMID- 9159835
TI  - Characteristics of long-term peritoneal dialysis survivors: 18 years experience
      in one center.
AB  - OBJECTIVES: Long-term experience of patients on peritoneal dialysis (PD) in
      general, and in diabetic patients specifically, is limited. Few patients have
      been followed on PD for over 8 years. Our aim was to evaluate and characterize
      long-term survivors (LTS) on PD for more than 100 months. A retrospective
      analysis of 20 patients who survived on PD for more than 100 months was
      performed. Data on long-term survivors was compared to data of 103 patients who
      died or switched to hemodialysis (HD) in less than 100 months. DESIGN: The study
      included all patients starting PD prior to 1 January 1986. Demographic,
      biochemical, dialysis prescription, and morbidity data were obtained on these
      patients. Characteristics of long-term survivors on PD (more than 100 months),
      was compared with those who died or switched to HD in less than 100 months, using
      Student t-test. SETTING: An experienced single center, university-based dialysis
      program. PATIENTS: 165 patients started PD at the University of Wisconsin prior
      to 1 January 1986. Forty three had type I diabetes mellitus and 24 had type II
      diabetes mellitus as the cause of their renal failure. RESULTS: Twenty patients
      survived on PD more than 100 months (LTS). Long-term survival of type I diabetic
      patients was seen in 7 of 43 patients at risk. Seventeen type I diabetics
      received renal transplants and ten died. 103 patients either died or switched to
      HD in less than 100 months. Long-term survivors were significantly younger,
      weighed less, had fewer episodes of peritonitis, fewer hospital days, and were
      prescribed more dialysis per kg body weight, than those who died or switched to
      HD prior to 100 months. CONCLUSIONS: Long-term survival on CAPD for longer than
      100 months is possible with survival periods up to 18 years in both males and
      females and in nondiabetics as well as patients with type I diabetes mellitus. No
      patient with type II diabetes mellitus survived longer than 100 months on CAPD.
      In comparison to short-term survivors, long-term survivors were characterized by
      being younger, weighing less, having fewer episodes of peritonitis, fewer
      hospital days, and were prescribed more dialysis/kg body weight.

PMID- 9159837
TI  - Coagulation- and fibrinolysis-related antigens in plasma and dialysate of CAPD
      patients.
AB  - OBJECTIVE: The present study is aimed at gaining insight into coagulation and
      fibrinolysis in the peritoneal cavity of patients on continuous ambulatory
      peritoneal dialysis (CAPD). For this purpose we measured coagulation- and
      fibrinolysis-related antigens in plasma and dialysate, comparing patients with
      and without peritonitis. DESIGN: Markers of activated coagulation and
      fibrinolysis in plasma and dialysate of CAPD patients were determined at
      different time points (0 hr, 2 hr, 4 hr) after infusion of the dialysis solution
      in the peritoneal cavity. Prothrombin fragment (F1 + 2), thrombin-antithrombin
      III complex (TAT), and fibrin monomer (FM) were chosen as parameters of activated
      coagulation. Fibrin degradation products (FbDP), D-dimer (DD), tissue-type
      plasminogen activator (t-PA), and plasminogen activator inhibitor type 1 (PAI-1)
      were measured as parameters for ongoing fibrinolysis. Beta 2-microglobulin,
      albumin, and IgG were used as marker proteins for the diffusion of proteins of
      intravascular origin into the peritoneal cavity. PATIENTS: Eleven clinically
      stable CAPD patients, who had not suffered from peritonitis during the last six
      months, and 5 CAPD patients with an acute episode of bacterial peritonitis were
      studied. RESULTS: In the dialysate of stable CAPD patients (n = 11) the
      concentration of activation markers of coagulation and fibrinolysis increased
      continuously with dwell time. After four hours we found remarkably high levels of
      the coagulation markers F1 + 2 (0.4 +/- 0.1 nmol/L), TAT (6.5 +/- 1.0 ng/mL), and
      FM (24.5 +/- 7.1 micrograms/mL), and the fibrinolysis markers DD (851 +/- 26
      ng/mL), FbDP (1.0 +/- 0.3 microgram/mL), t-PA (3.3 +/- 0.8 ng/mL), and PAI-1 (2.6
      +/- 1.2 ng/mL). The dialysate-to-plasma (D/P) ratios of all of these antigens
      were significantly higher compared to the D/P ratios of proteins with similar
      molecular weight, which are not produced intraperitoneally (beta 2-microglobulin,
      albumin, and IgG). These findings point to a local, thrombin-induced
      intraperitoneal fibrin generation during regular CAPD. Compared with clinically
      stable CAPD patients, the patients with bacterial peritonitis (n = 5) had
      significantly higher levels of F1 + 2 (5.3 +/- 1.6 nmol/L), TAT (57.8 +/- 10.7
      ng/mL), FM (972 +/- 3.2 micrograms/L), FbDP (16.4 +/- 2.9 micrograms/L), and PAI
      1 (7.3 +/- 2.4 ng/mL) in the dialysate (4-hr dwell time), and a 2.4-times higher
      ratio between FM and FbDP. These results can be interpreted as an intraperitoneal
      imbalance between coagulation and fibrinolysis during peritonitis. CONCLUSION:
      Our study demonstrates a high intraperitoneal fibrin formation, not only during
      peritonitis but also in clinically stable CAPD patients. The remarkably high
      levels of coagulation (F1 + 2, TAT, FM) and fibrinolysis (FbDP, DD, t-PA, PAI-1)
      related antigens in the dialysate of patients without peritonitis cannot be
      explained by transport from plasma into the peritoneal cavity and may reflect a
      high rate of intraperitoneal fibrin turnover. The balance between peritoneal
      generation and degradation of fibrin is obviously disturbed in CAPD patients with
      peritonitis, who had significantly higher levels of coagulation markers in the
      dialysate and a higher ratio between FM and FbDP.

PMID- 9159838
TI  - Oxidative metabolism of polymorphonuclear leukocytes in continuous ambulatory
      peritoneal dialysis.
AB  - OBJECTIVE: To evaluate the oxidative metabolism of polymorphonuclear leukocytes
      (PMNL) in continuous ambulatory peritoneal dialysis (CAPD) patients compared with
      those of hemodialysis (HD) patients, chronic renal failure (CRF) patients not yet
      on dialysis, and healthy controls; and to discover factors contributing to the
      oxidative function in CAPD patients. PATIENTS: Thirty-five CAPD, 22 HD, 11 CRF
      patients were assessed; all were free from infections at the time of examination.
      Thirty-one healthy volunteers served as controls. METHODS: The oxidative
      metabolism was estimated by the production of superoxide anion, which was
      detected by luminol-dependent zymosan stimulated chemiluminescence (CL) with
      whole blood assessment. The volume of superoxide production equivalent to 1 mL of
      circulating blood (T-CL), that equivalent to 10(4) neutrophils (CL/N) and the
      velocity of superoxide production (V-CL), were measured as parameters for the
      oxidative function of PMNL. RESULTS: There were no differences in all CL
      parameters between CAPD and HD patients. T-CL and CL/N of dialysis patients were
      equal to controls but those of CRF patients were significantly decreased. V-CL of
      dialysis patients, as well as CRF patients, was smaller than that of controls but
      the difference was not significant. Among nutritional status, degree of anemia,
      dialytic efficacy and duration of dialysis in CAPD patients, only serum albumin
      concentration (Alb) correlated well to all CL parameters. Hypoalbuminemic
      patients (Alb < 3.6 g/dL, n = 20) had significantly decreased T-CL and CL/N
      compared to normoalbuminemic patients (Alb > or = 3.6 g/dL, n = 15), and
      decreased CL/N and V-CL compared to controls. No differences in CL parameters
      were observed between the patients with a history of peritonitis (n = 15) and
      without a history of peritonitis (n = 20). CONCLUSIONS: Oxidative metabolism of
      PMNL in CAPD patients was maintained with respect to superoxide productive
      volume, while the oxidative velocity was relatively impaired. Furthermore, it
      seems that albumin has a great influence on the oxidative metabolism of PMNL in
      CAPD patients.

PMID- 9159839
TI  - Adequate dialysis? Measurement of KT/V in a pediatric peritoneal dialysis
      population.
AB  - OBJECTIVE: To measure the urea and creatinine kinetics in a pediatric population.
      PATIENTS AND METHODS: In 19 children treated with peritoneal dialysis (PD) KT/V,
      urea and creatinine clearances (Ccr) were measured. Thirteen children were on
      continuous ambulatory peritoneal dialysis (CAPD) and 6 on highly intermittent
      peritoneal dialysis (NIPD). RESULTS: Mean KT/V per week was 2.31 +/- 0.78 and
      mean creatinine clearance 74 +/- 47 L/week/1.73 m2. There was no difference in
      dialytic KT/V between patients treated with CAPD and NIPD (1.75 +/- 0.21 vs 1.76
      +/- 0.50). The correlation between KT/V urea and creatinine clearance was 0.9 (p
      < 0.001). There was a clear relationship of these parameters with residual renal
      function, but not with age or blood urea level. A weak positive correlation was
      found with serum albumin and protein intake. CONCLUSIONS: Mean KT/V in this
      patient group was higher than the values reported for most adult patient groups.
      Residual renal function considerably contributes to this high KT/V. It is not
      clearly defined which KT/V should be aimed for, since criteria for adequate
      dialysis are multifactorially determined and therefore difficult to interpret.

PMID- 9159840
TI  - Chronic administration of iron dextran into the peritoneal cavity of rats.
AB  - OBJECTIVE: To determine the influence of chronic iron dextran administrations
      into the peritoneal cavity of rats on function and anatomy of the peritoneal
      membrane, as well as on erythropoiesis and serum iron. DESIGN: Prospective
      randomized animal study. SETTING: Animal laboratory. ANIMALS: 36 Sprague-Dawley
      rats. INTERVENTIONS: The rats were divided into three groups (n = 12). The
      animals were given standard 1.5% Dianeal (control group) or 1.5% Dianeal
      containing iron dextran in a concentration of 2 mg/L [low-dose group (LDG)] or 10
      mg/L [high-dose group (HDG)]. MAIN OUTCOME MEASURES: On the 8th day, at 3 months,
      and at 6 months a 2-hour peritoneal equilibration test (PET) and blood tests
      including hematocrit, serum iron, and total iron-binding capacity (TIBC) were
      done. After the final PET at 6 months, the peritoneal membrane was evaluated by
      gross inspection and by light microscopy. RESULTS: Hematocrit and serum iron
      levels increased only in the HDG and LDG. Peritoneal transport of small solutes
      decreased significantly in the HDG compared to baseline. All cases of the HDG
      group revealed peritoneal adhesions and fibrosis around the peritoneal catheter
      as well as massive iron deposits on the peritoneum. Similar but less pronounced
      changes were found in the LDG. CONCLUSIONS: These findings suggest an efficient
      absorption of iron from the peritoneal cavity of rats, however, dialysate iron
      dextran concentrations of 2 mg/L or greater are toxic to the peritoneal membrane.
      Therefore, future studies should be performed to determine the minimal effective
      and nontoxic iron dextran concentrations for intraperitoneal administration.

PMID- 9159841
TI  - Insulin stimulates the activity of Na+/K(+)-ATPase in human peritoneal
      mesothelial cells.
AB  - OBJECTIVE: To assess the effect of insulin on the Na+/K(+)-ATPase expression and
      activity in human peritoneal mesothelial cells (HPMC). METHODS: HPMC were
      isolated from the omental tissue of non-uremic patients, grown to confluence and
      rendered quiescent by serum deprivation for 24 hours. The activity of Na+/K(+)
      ATPase was determined by measuring the ouabain-sensitive 86Rb uptake. To assess
      whether the effect of insulin was related to changes in [Na+]i the sodium influx
      was measured with 22Na and the activity of Na+/K(+)-ATPase was assessed in the
      presence of amiloride. Expression of Na+/K(+)-ATPase alpha 1,alpha 2 and beta 1
      subunit mRNAs was determined by RT/PCR. RESULTS: Exposure of HPMC to insulin
      resulted in a time- and dose-dependent increase in the Na+/K(+)-ATPase activity.
      After 60 minutes the ouabain-sensitive 86Rb uptake (cpm/10(4) cells) was
      increased from 6650 +/- 796 in control cells to 9763 +/- 1212 in HPMC exposed to
      100 mU/mL insulin (1.5-fold increase; n = 4, P < 0.05). In addition, incubation
      of HPMC with 100 mU/mL insulin resulted in a time-dependent increase in the 22Na
      influx. Pre-exposure of HPMC to 1mM amiloride reduced the activity of Na+/K(+)
      ATPase but did not block the stimulatory effect of insulin. RT/PCR analysis
      revealed that HPMC constitutively expressed alpha 1- and beta 1-subunit mRNAs
      while the alpha 2-subunit mRNA was barely detectable. Exposure of HPMC to insulin
      for up to 24 hours was not associated with any changes in the expression of
      either alpha 1, alpha 2 or beta 1-subunit. CONCLUSION: Insulin stimulates the
      Na+/K(+)-ATPase activity in HPMC in a time- and dose-dependent manner. This
      effect appears to mediated by an increase in [Na+]i and is not related to
      alterations in Na+/K(+)-ATPase subunit mRNAs expression.

PMID- 9159842
TI  - Omental entrapping of the peritoneal dialysis catheter solved by a laparoscopic
      approach.

PMID- 9159843
TI  - The role of curettage in the care of persistent exit-site infection in CAPD
      patients.

PMID- 9159844
TI  - Pro-inflammatory activity of phospholipase A2 in CAPD patients with and without
      peritonitis.

PMID- 9159845
TI  - The necessity of adjusting dialysate volume to body surface area in pediatric
      peritoneal equilibration tests.

PMID- 9159846
TI  - A prospective study of vancomycin-(Vancoled-)induced chemical peritonitis in CAPD
      patients.

PMID- 9159847
TI  - Nasal carriage of Staph. aureus in peritonitis and exit-site infections.

PMID- 9159848
TI  - Sotalol-induced Torsade de pointes in a CAPD patient--successful treatment with
      intermittent peritoneal dialysis.

PMID- 9159849
TI  - Comparisons of peritoneal transport between insulin-dependent and noninsulin
      dependent and noninsulin-dependent diabetic peritoneal dialysis patients.

PMID- 9159850
TI  - Peritoneal dialysis catheter malfunction due to compartmentalization.

PMID- 9159851
TI  - Stability of iron concentrations in peritoneal dialysis solution bags.

PMID- 9159853
TI  - Literature. January-February 1997.

PMID- 9159852
TI  - Videolaparoscopy with partial omentectomy in patients on peritoneal dialysis.

PMID- 9159854
TI  - Acute abdomen. The history.
AB  - Correct decision, when managing the acute abdomen in children, are based on
      careful clinical assessment. An accurate history and a detailed examination will
      provide more information than a multitude of investigations. The chronological
      order to appearance and the progression of each individual symptom must be
      obtained. Consideration of these dynamic changes will often yield an accurate
      diagnosis. This article outlines a structured approach to history taking and
      details the common causes of acute abdomen in childhood.

PMID- 9159855
TI  - Acute abdomen. The physical examination.

PMID- 9159856
TI  - Acute abdomen. Laboratory evaluation and imaging.
AB  - The child with an acute abdomen requires a thorough history and physical
      examination followed by a focused laboratory and imaging evaluation. The
      laboratory evaluation is more beneficial in determining management than in
      establishing diagnosis. Ultrasonography has become increasingly useful in the
      evaluation of the child with acute abdominal pain.

PMID- 9159857
TI  - Acute abdomen. When to operate immediately and when to observe.
AB  - When to operate immediately, when to observe, and when not to operate at all
      represent major challenges in the management of a child with an acute abdomen.
      This article is an overview of the subject from symptom to diagnosis, evaluation,
      and preparation for the surgical intervention. Tables provide examples of
      conditions requiring prompt surgical intervention and relative surgical urgency;
      pathologies suitable for (initial) nonsurgical management; and clinical pictures
      where surgical intervention is not indicated. Factors that influence the timing
      of operation are provided, as is the differential diagnosis between intestinal
      strangulation and obstruction. Brief notes highlight four important causes of
      acute abdomen in children acute appendicitis, malrotation with volvulus, Meckel's
      diverticulum, and intussusception. These as well as other intraabdominal
      pathologies are illustrated by means of surgical photographs. The acute abdomen
      is a clinical diagnosis. Other diagnostic modalities have merely supporting
      roles. The decision to operate is based primarily on the results of a good
      history and thorough physical examination(s).

PMID- 9159858
TI  - Acute abdomen. The role of laparoscopy.
AB  - The child with an acute abdomen presents the perfect opportunity to take
      advantage of the benefits of minimal-access surgery. There are a wide variety of
      conditions, acquired and congenital, for which minimal-access techniques provide
      the distinct advantages of a cost-effective diagnosis and therapy with minimal
      discomfort for the patient. In the present report, the management of children
      with abdominal pain of unclear etiology is outlined, along with discussions of
      the value of minimal-access surgery in appendicitis and other conditions. Several
      algorithms are provided as a guideline for suggested approaches to management.

PMID- 9159859
TI  - Acute abdomen. How to balance costs and quality care.
AB  - The costs of health care have been escalating at such a rapid rate, especially
      during the past decade, that not only in the United States but throughout the
      Western World, stringent efforts are being made to control and decrease costs.
      Physicians, through their orders, are responsible for the major part of
      escalating costs. Sophisticated modern technology plays a large role in medical
      expense, and will need to be used very discriminately if costs are to be
      controlled and decreased. Although modern medical technology frequently enhances
      diagnosis and management, even physicians experienced with its use will attest to
      its overutilization. Pediatric surgeons and other physicians at times will
      substitute technology for the basics of history taking and meticulous physical
      examination. Controlling and lowering the cost of children's surgical care can be
      achieved in balance and in concert with the provision of optimal care.

PMID- 9159860
TI  - Acute abdomen. Special considerations for the neurologically and immunologically
      impaired child.
AB  - The neurologically or immunologically impaired child suspected of having an acute
      abdomen presents a formidable challenge. However, a thorough understanding of the
      underlying pathophysiology of the disease on the normal host response to an
      intraabdominal disease permits early recognition and initiation of treatment.
      Classic findings of the acute abdomen are the exception rather than the rule.
      These children require constant vigilance and repeated examination. Radiographic
      studies should be used early and often. The advent of minimally invasive surgical
      techniques offers the opportunity to intervene early both diagnostically and
      therapeutically. Ultimately, however, the best outcomes will be achieved by those
      who employ sound surgical judgment and avoid unnecessary therapeutic delay owing
      to inexperience, inattention, or indecision.

PMID- 9159861
TI  - Acute abdomen. The teenage girl.
AB  - The evaluation of abdominal pain in the adolescent female is a common and often
      challenging problem. The unique anatomy and biology of the postmenarcheal
      teenager necessitates the consideration of a broad variety of additional
      genitourinary problems not encountered in the male. Further complicating this
      issue, the differential diagnoses involves not only pathological considerations,
      but normal physiological processes that may, in and of themselves, be
      symptomatic. One must be skillful enough to avoid unnecessary intervention, while
      aggressively pursuing significant intraabdominal problems. Occasionally, however,
      only invasive modalities will enable definitive diagnosis, and facility with
      these techniques significantly enhances both diagnostic and therapeutic
      capabilities in these patients.

PMID- 9159862
TI  - Acute abdomen. Outcomes.
AB  - The outcome for children with common surgical conditions that cause an acute
      abdomen is discussed. These conditions include appendicitis, intussusception,
      malrotation, inflammatory bowel disease, intestinal obstructions, and nonorganic
      pain. Emphasis is placed on surgical intervention and disease processes that
      significantly affect outcome. The outcome of many of the diseases discussed is
      strongly influenced by the timing of diagnosis and treatment. These children
      should have prompt care and intervention to prevent morbidity and mortality. In
      addition, many children who present with common pediatric surgical emergencies
      have other medical conditions and are best treated in an environment that has a
      multidisciplinary team to handle their care and decrease the long-term
      complications.

PMID- 9159864
TI  - Reversible organization of mitochondria into associations as a factor regulating
      respiration.
AB  - Mitochondria in the form of associations close to their state in the quiescent
      cell were obtained in rat liver homogenate under physiological for cytosol
      concentrations of potassium and calcium ions and small dilution of tissue.
      Associations in such homogenates are stable on storage in ice for several hours.
      Dissociation of associations is induced by dilution of the homogenate, addition
      of EDTA, or by administration of adrenaline to the animal. Respiration rate is
      increased and ADP/O ratio is decreased when associations dissociate. The observed
      increase in respiratory rate induced by adrenaline administration in vivo is
      decreased or abolished when associations are dissociated in the incubation medium
      induced by influences in vitro. This is due to hyperactivation of respiration
      which leads to inhibition of succinate oxidation by oxaloacetate. Under the
      conditions preserving the associations of mitochondria a close interaction of
      oxidative and transamination processes is observed as well as a broader range of
      metabolic states of mitochondria than in standard preparations which dissipate
      into single granules on isolation in sucrose, high dilution, and washing.

PMID- 9159863
TI  - Secretory heat-shock protein of the thermotolerant yeast Hansenula polymorpha.
      Identification and comparative characteristics.
AB  - Thirteen investigated strains of ascomycetous yeasts able to produce secretory
      heat-shock proteins (sHSPs) do not response equally to a high temperature by
      induction of the synthesis and secretion of these proteins. In this respect the
      above yeasts can be divided into three groups having a positive (I), a negative
      (II), and an indefinite reaction (III) to the heat shock. The thermotolerant
      yeast Hansenula polymorpha belongs to the first group. In this yeast heat shock
      induces the synthesis and secretion of sHSP gp280. This new representative
      differs from known sHSPs in molecular mass and subunit composition. In other
      respects (glycosylation, mainly extracellular localization, and the character of
      export into the culture medium) it displays similar properties.

PMID- 9159865
TI  - Inhibition of Fe(2+)-induced lipid peroxidation in egg yolk lipoproteins by
      metallothionein.
AB  - Rat hepatic apometallothionein and to a lesser extent Zn-metallothionein inhibit
      Fe(2+)-dependent lipid peroxidation (LPO) in suspensions of egg yolk
      lipoproteins. ZnCl2 or its combination with cysteine at corresponding
      concentrations activate LPO.

PMID- 9159866
TI  - Seasonal changes in myoglobin content in muscles of hibernating Yakutian ground
      squirrels.
AB  - Myoglobin content in skeletal muscles of the Yakutian ground squirrel Citellus
      undulatus was measured during different periods of the annual life cycle: in
      active animals in summer, and in hibernating and awake animals in winter. It was
      found that the Mb content in winter, irrespective of the state of the animal
      (hibernating or awake), is 2.5-3-fold higher than in summer. Analysis of
      biochemical data available in the literature suggests that the increase in Mb
      content in winter is most probably related to a high oxygen demand of muscles at
      the first stage of arousal when the body temperature rises from 0 to 10-12
      degrees C (non-shivering thermogenesis or thermoregulatory tonus). At this stage,
      the oxygen-dependent processes in muscles proceed under conditions of blocked
      peripheral blood flow and failure of anaerobic glycolysis.

PMID- 9159867
TI  - Induction and repression of genes of the rat small intestine mucosa with excess
      and insufficiency of alimentary iron.
AB  - Three-month-old Wistar rats were fed with either an iron-deficient diet for 21
      days or an iron-excessive diet for 10 days. Fifty thousand clones of a cDNA
      library of small intestine mucosa were hybridized with two radioactive samples
      synthesized on mRNA from the small intestine of rats fed with iron-excessive or
      iron-deficient diets. As a result, genes were found with mRNA level depending on
      the content of alimentary iron. Iron deficiency increased the mRNA level of genes
      of apolipoprotein AIV and class 1 antigen and decreased the mRNA level of the
      apolipoprotein AI gene and of an unknown gene, while no change was found in the
      mRNA level of the gene of fatty acid-binding protein. Excess of dietary iron
      resulted in the increase in mRNA of this gene and in a decrease in the
      apolipoprotein AI gene and in the unknown gene. The mRNA of apolipoprotein AIV
      did not change. The data indicate that changes in the level of alimentary iron
      influence the expression of genes involved in metabolism of lipids.

PMID- 9159868
TI  - Three dose-dependent stages of the effect of copper ions on functional activity
      of biological systems.
AB  - The dose-dependent effects of copper sulfate on the proliferation and functional
      activity of the genome of liver cells and of algae in vivo and the activity of
      RNA-polymerase and glucose-6-phosphatase and formation of malonic dialdehyde in
      vitro were investigated. Administration of various doses of copper sulfate causes
      a dose-dependent three-phase response of biological systems comprising a
      stimulation phase, a latent phase, and a phase of inhibition. The degree of
      manifestation of the three-phase response depends on the functional activity of
      the biological system. The consecutive dose-dependent binding of metal ions with
      components of cells forms the basis of the three-phase response to copper ions.

PMID- 9159869
TI  - Products of the reaction of cholesterol with hypochlorite anion.
AB  - Products of the reaction of cholesterol with hypochlorite (OCI) in various
      systems (egg phosphatidylcholine liposomes, low-density lipoproteins, and aqueous
      colloidal dispersion of cholesterol) were separated and analyzed by TLC, HPLC,
      and gas chromatography-mass spectrometry. The reactions of hypochlorite with
      cholesterol result in the same reaction products in all treated systems. Eighteen
      fractions were isolated from the reaction mixture by normal-phase HPLC in hexane
      isopropanol (95:5 v/v); these were then examined by gas chromatography-mass
      spectrometry. Six products less polar than cholesterol were isolated from the
      reaction mixture; two of them were identified as 4,6-cholesten-3-one and 4
      cholesten-3,6-dione. Among the oxidation products more polar than cholesterol,
      nine compounds were identified; they are 5,7-cholestadien-3 beta-ol,3,5
      cholestadien-7-one, 4-cholesten-3 beta, 6 beta-diol, 5-cholesten-3 beta, 7 beta
      diol, cholestan-3 beta, 5 alpha, 6 beta-triol, 5 alpha-cholestan-3 beta-ol-6-one,
      5-cholesten-3 beta-ol-7-one, 5 alpha, 6 alpha-epoxycholestan-3 beta-ol, and 5
      alpha-cholesten-3,6-dione.

PMID- 9159870
TI  - Transferrin and ferritin modulate the activity of brain calcium-calmodulin
      dependent phosphodiesterase.
AB  - The effect of the key iron homeostasis proteins transferrin and ferritin on the
      activity of partially purified brain calcium-calmodulin-dependent
      phosphodiesterase (CaM-PDE, EC 3.4.1.17) were studied. Transferrin and ferritin
      were found to be potent natural activators of CaM-PDE. The key factor determining
      the degree of activation by these proteins is their saturation with iron:
      apotransferrin activated CaM-PDE 6-7-fold; iron-poor brain ferritin and liver
      apoferritin (taken for comparison) activated the enzyme 4-5- and 2-fold,
      respectively. Diferric transferrin and iron-rich liver ferritin had no effects on
      the enzyme activity. Transferrin and ferritin (both in apo- and iron-saturated
      forms) did not change the activity of calmodulin-phosphodiesterase complex. The
      data suggest that apotransferrin and iron-poor transferrin are involved in the
      regulation of cyclic nucleotide content in nervous tissue.

PMID- 9159871
TI  - Purification and characterization of serine proteinase of the Glu,Asp-specific
      enzyme family from Thermoactinomyces species.
AB  - Enzyme catalyzing hydrolysis of a substrate of Glu,Asp-specific proteinases (Z
      Glu-pNA) and cleaving bond Glu13-Ala14 in the oxidized insulin B chain was
      purified to homogeneity from the culture medium of Thermoactinomyces species
      using hydrophobic chromatography on phenyl-Sepharose CL 4B as the key
      purification step. The molecular weight of the proteinase is 23 kD. The enzyme is
      completely inhibited by diisopropyl fluorophosphate and is stable at pH 5-11. The
      pH optimum for the hydrolysis of azocasein as substrate is 8.5. The temperature
      optimum for proteolytic activity is 55 degrees C. The N-terminal sequence of the
      proteinase is: Ser-Val-Leu-Gly-Thr-Asp-Glu-Arg-Thr-Arg-Val-Thr-Asn-Thr-Thr-Thr
      Tyr-Pro- Tyr- Trp-.

PMID- 9159873
TI  - Standardized and extended catalog of major proteins of the human kidney.
AB  - A new version of a two-dimensional electrophoretic catalog of proteins of the
      human kidney and of various morphological and functional structures of the human
      kidney is presented; it contains information about 179 polypeptides. The
      following proteins were identified: crystallin, albumin, mitochondrial superoxide
      dismutase, actin, fatty acid-binding protein, alpha-ATP-synthase, and
      transferrin. Some protein groups are specific for certain morphological
      structures.

PMID- 9159872
TI  - Interaction of the E. coli alkaline phosphatase precursor with model phospholipid
      membranes.
AB  - An interaction of a precursor of the E. coli secreted alkaline phosphatase
      (prePhoA) containing a signal peptide and model bilayer membranes prepared from
      the lipids of E. coli has been studied. The interaction was evaluated by
      monitoring of the state of the lipid phase by fluorescence spectroscopy. The role
      of the signal peptide in this process was evaluated by a comparative study of the
      interaction of the mature alkaline phosphatase which does not contain the signal
      peptide with the model membranes. The precursor was shown to be inserted into the
      lipid bilayer since the fluorescence anisotropy of a hydrophobic probe,
      diphenylhexatriene, was enhanced. The intensity of the process is determined by
      the presence of the signal peptide and depends on the pH of the medium. The data
      indicate that the mature polypeptide chain of the enzyme also has affinity for
      the membrane.

PMID- 9159874
TI  - Recognition and conversion of single- and double-stranded oligonucleotide
      substrates by 8-oxoguanine-DNA glycosylase from Escherichia coli.
AB  - The substrate specificity of 8-oxoguanine-DNA glycosylase was studied. The data
      showed for the first time that the enzyme can cleave single-stranded
      deoxyoligonucleotides containing an 8-oxoG link. The values of K(m) and Vmax for
      a range of single-stranded and double-stranded oligonucleotides (23 bp)
      containing 8-oxoG at different positions of one chain. These parameters
      consistently depended on the position of 8-oxoG in single-stranded or double
      stranded substrates. A possible mechanism responsible for substrate recognition
      by 8-oxoguanine-DNA glycosylase is described.

PMID- 9159875
TI  - Development of immunoenzymatic reactions of peptides using recombinant hybrid
      proteins.
AB  - A recombinant hybrid protein comprising the bacteriophage fr coat protein, a
      short linker, and atrial natriuretic factor (ANF) as well as native and
      recombinant phage coat proteins, ANF, and variants of the hybrid recombinant
      protein were used in the development of various immunological reactions including
      immunization, preparation of affinity columns, purification of antibodies,
      synthesis of conjugates, and immunoenzyme assay of ANF and the recombinant
      protein. The hybrid protein is effective in competitive assay of ANF and other
      constructs that include the phage protein.

PMID- 9159876
TI  - Overexpression of the gene of ribosomal protein L30 from Thermus thermophilus and
      crystallization of the recombinant protein.
AB  - Ribosomal protein L30 from Thermus thermophilus was overexpressed in E. coli
      cells. The recombinant protein was isolated and crystallized. The crystals belong
      to the spatial group P3(1) 12, and their crystallographic parameters are not
      different from those of crystals obtained earlier from the ribosomal protein
      isolated from T. thermophilus.

PMID- 9159877
TI  - The role of the sodium cycle of energy coupling in the emergence and persistence
      of natural foci of modern cholera.
AB  - A hypothesis on the appearance and persistence of natural foci of cholera based
      on ecological and bioenergetic features of the process has been developed. The
      main causes of persistence and propagation of modern cholera are: 1) inability of
      various bacteria, including the genus Vibrio and many cyanobacterial species, to
      perform energy coupling, depending on external conditions, by means of two cycles
      (the proton and sodium cycles); induction of the sodium cycle of energy coupling
      increases the resistance of bacteria to various environmental factors, such as
      high concentrations of sodium, alkaline pH, and a high proton conductance of
      coupling membranes [1], and probably the virulence of the vibrios; 2) development
      of cyanobacteria in an aquatic environment enriched with Na+ accelerates
      alkalization of the medium and stimulates the development of the community of
      cyanobacteria with Vibrio cholerae, an autochthonous inhabitant of saline water
      bodies and marine shallow waters; 3) salinization of water bodies accelerates
      their blooming and enriches them with soluble organic matter, a substrate for
      vibrios inhabiting the biotope; 4) further propagation of cholera infection is
      related to eating heat-untreated hydrobionts from blooming water bodies [2].

PMID- 9159878
TI  - The evolution of gene expression, structure and function of transthyretin.
AB  - Thyroxine, the most abundant thyroid hormone in blood, partitions into lipid
      membranes. In a network-like system, thyroxine-binding plasma proteins counteract
      this partitioning and establish intravascular, protein-bound thyroxine pools.
      These are far larger than the free thyroxine pools. In larger eutherians,
      proteins specifically binding thyroxine are albumin, transthyretin, and thyroxine
      binding globulin. Some binding of thyroxine can also occur to lipoproteins.
      During evolution, transthyretin synthesis first appeared in the choroid plexus of
      the stem reptiles, about 300 million years ago. Transthretin synthesis in the
      liver evolved much later, independently, in birds, eutherians and some marsupial
      species. Analysis of 57 human transthyretin variants suggests that most mutations
      in transthyretin are not compatible with its normal metabolism and lead to its
      deposition as amyloid. Analysis of transthyretin or its gene in 20 different
      species shows that evolutionary changes of transthyretin predominantly occurred
      near the N-termini. A change in RNA splicing between exon 1 and exon 2 led to a
      decrease in hydrophobicity and length of the N-termini. It is proposed that the
      selection pressure producing these changes was the need for a more effective
      prevention of thyroxine partitioning into lipids. Lipid pools increased during
      evolution with the increases in relative sizes of brains and internal organs and
      changes in lipid composition of membranes in ectothermic and endothermic species.

PMID- 9159879
TI  - Characterization of yellowfin tuna (Thunnus albacares, Scombroidei) tryptophan
      hydroxylase.
AB  - Tryptophan hydroxylase (EC 1.14, 16.4) was purified from yellowfin tuna liver and
      properties of this enzyme were compared with those of tryptophan hydroxylase from
      some other species (mouse mastocytoma and rat brain-stem). The molecular weight
      of the yellowfin tuna enzyme was estimated to be about 280,000 Da. This value is
      similar to that for the enzymes from mouse mastocytoma and rat brain-stem. On SDS
      polyacrylamide gel electrophoresis analysis, yellowfin tuna enzyme was estimated
      to be about 96,000 Da. This value is different from that for the enzymes from
      mouse mastocytoma (53,000 Da) and rat brain-stem (59,000 Da) and suggests that
      yellowfin tuna enzyme may be a dimer of identical subunits of Mr 96,000 Da.

PMID- 9159880
TI  - Comparative study of carbohydrate portion of gastrointestinal mucins using enzyme
      linked lectin-binding assay (ELLA).
AB  - We improved the enzyme-linked lectin-binding assay (ELLA) to determine the
      differences in the carbohydrate chains of corpus, antral, duodenal ant colonic
      rat mucins. First we have improved the optimal conditions of this assay for
      mucins; ELLA makes possible the detection of 1.5 ng of hexose in rat
      gastrointestinal mucins (5-7 ng of mucins). Salt concentrations of several dozens
      mM are required for mucin coating on the plate. Non-ionic detergents diminish the
      adsorption of mucins onto the plate. Secondly we tested a set of 8 lectins to
      compare their binding to the gastrointestinal mucin samples. It is possible to
      detect crude mucins as well as purified mucins using ELLA. Gastric mucins have
      less Tn-antigen than duodenal and colonic mucins. Corpus and duodenal mucins have
      more of the H-type 2 chain than antral and colonic mucins.

PMID- 9159882
TI  - Purification and characterization of myofibril-bound serine proteinase from carp
      Cyprinus carpio ordinary muscle.
AB  - 1. A novel myofibril-bound serine proteinase (MBP) has been purified from
      ordinary muscle of the carp Cyprinus carpio. 2. It was solubilized from the
      myofibril fraction with acid treatment (under the conditions of 0.6 M KCl, pH
      4.0), then purified by column chromatographic steps on Ultrogel AcA 54, and
      Arginine-Sepharose 4B. 3. The purified enzyme revealed a single protein band on
      SDS-PAGE, and its molecular mass was estimated to be 30 kDa by SDS-PAGE and gel
      filtration. 4. The optimum pH and temperature of the enzyme were 8.0 and 55
      degrees C, respectively, when Boc-Phe-Ser-Arg-MCA and casein were used as
      substrates. 5. The enzyme hydrolyzed Boc-Gln-Arg-Arg-MCA most rapidly, and also
      hydrolyzed the substrates for trypsin-type proteinase, but not for chymotrypsin.
      The enzyme was inhibited by serine proteinase inhibitors such as DFP, STI and
      leupeptin. These results suggested that the enzyme was a trypsin-type serine
      proteinase. 6. Boc-Phe-Ser-Arg-MCA hydrolyzing activity of the purified enzyme
      was reduced by addition of NaCl, but the caseinolytic activity and Boc-Phe-Ser
      Arg-MCA hydrolyzing activity of the partially purified enzyme were activated by
      NaCl.

PMID- 9159881
TI  - Changes in IP3 metabolism during skeletal muscle development in vivo and in
      vitro.
AB  - We have investigated whether IP3 metabolism presents particular changes during
      critical stages of muscle development. With this aim, we have measured IP3
      formation through phospholipase C activity, IP3 removal through IP3 5-phosphatase
      and IP3 3-kinase activities, as well as IP3 mass, during myogenesis in vivo and
      in vitro. In developing rat skeletal muscle, both IP3 3-kinase and 5-phosphatase
      activities were relatively constant from embryonary day 15, the earliest age
      studied to postnatal day 10; 5-phosphatase decreased upon further development. A
      transient, major increase in phospholipase C activity was evident at embryonary
      day 18 while a non-significant increase in IP3 mass was detected at this
      embrionary age. In rat skeletal muscle in primary culture, all enzyme activities
      as well as the mass of IP3 increased significantly in myotubes compared to
      myoblasts. Myotubes incubated with calcitonin gene-related peptide, responded
      with a transient increase in IP3 mass after 2 to 10 sec; the CGRP-induced
      increase being completely blocked by U-73122, a phospholipase C inhibitor.
      Furthermore, IP3 mass increased within 1 hr after exposure to differentiating
      agents of both RCMH cells, a line derived from normal human skeletal muscle, and
      C2C12 cells. These results indicate that changes in IP3 metabolism can be
      correlated to critical stages of muscle development and differentiation,
      suggesting a possible role for IP3 in these processes.

PMID- 9159883
TI  - Isolation of low density lipoprotein subfraction containing apolipoprotein B-like
      protein from Japanese eel Anguilla japonica plasma using dextran sulfate
      cellulose.
AB  - Japanese eel (Anguilla japonica) possessed a unique lipoprotein profile in their
      plasma, reflecting high utilization of lipids. Low density lipoprotein (LDL)
      fraction isolated at the densities from 1.006 to 1.085 g/ml comprised the
      heterogeneous components with molecular weight (Mr) 1200 K, 470 K, and 250 K. LDL
      subfraction with Mr 1200 K was completely adsorbed to dextran sulfate cellulose
      (DSC) column which had been developed for LDL apheresis treatment of the patients
      with familial hypercholesterolemia, while LDL subfractions with Mr 470 K and 250
      K had no affinity for the DSC column. LDL subfractions with Mr 470 K and 250 K
      were floated and settled, respectively, by centrifuging the unbound fraction of
      DSC column at a density of 1.063 g/ml. LDL subfraction with Mr 1200 K possessed
      apolipoprotein (apo) B-like protein of Mr 230 K, while apo A-I- and A-II-like
      proteins of Mr 25 K and 14 K were the main components in LDL subfractions with Mr
      470 K and 250 K. The presence of apo B-like protein seemed to be responsible for
      the adsorption of LDL subfraction with Mr 1200 K for the DSC column. LDL
      subfractions with Mr 470 K and 250 K seemed to belong to high density lipoprotein
      (HDL) with respect to molecular weights and apolipoprotein features. To our
      knowledge, this is the first report of the separation of LDL and HDL from the
      plasma of Japanese eels using the DSC column.

PMID- 9159885
TI  - L-cysteine metabolism in guinea pig and rat tissues.
AB  - Rhodanese, gamma-cystathionase and 3-mercaptopyruvate sulfurtransferase
      activities were examined in guinea pig and rat liver, kidney and brain. In the
      liver of both species rhodanese showed the same high range of activity but in
      guinea pig kidney and brain a slightly lower level was determined than that in
      corresponding rat tissues. The 3-mercaptopyruvate sulfurtransferase and gamma
      cystathionase activities in all the investigated tissues of guinea pig were
      significantly lower than those in rat. The sulfane sulfur pool, a source of
      sulfur transferred by rhodanese, can be augmented in vitro in guinea pig liver,
      but not in rat liver when 3-mercaptolactate-cysteine disulfide is used as a
      substrate of gamma-cystathionase.

PMID- 9159884
TI  - A lipoprotein secreted by cultured hepatocytes of silver or yellow eel:
      comparison with their plasma lipoproteins.
AB  - Cultured hepatocytes of silver eel actively secreted only chylomicron-like
      lipoprotein. The rate of secretion per mg cellular protein per 24 hr was 2.2
      times higher compared with that by yellow eel hepatocytes. Silver eel hepatocytes
      secreted lipids 2.5 times higher through the lipoprotein than yellow eel
      hepatocytes. Main lipid was triacylglycerol in either secreted lipoprotein and
      composition of apolipoproteins of both secreted lipoproteins was the same. The
      incorporation of 3H-leucine into the lipoprotein secreted by silver eel
      hepatocytes was 2.4 times higher, but that of 14C-acetate was not significantly
      different. Protein and lipids composition of plasma lipoproteins of silver eel
      was significantly higher and lower compared with those of yellow eel,
      respectively. We suggest that the secreted lipoprotein of silver eel hepatocytes
      transport much more lipids to other tissues than that of yellow eel hepatocytes.

PMID- 9159886
TI  - Isolation and characterization of a cDNA encoding a Xenopus immunoglobulin
      binding protein, BiP (grp78).
AB  - We have isolated a full-length cDNA clone encoding a Xenopus laevis
      immunoglobulin binding protein (BiP; also called glucose-regulated protein or
      grp78). The Bip cDNA sequence includes an open reading frame of 1,965 bp encoding
      a 655 amino acid protein with an N-terminal hydrophobic leader sequence and a C
      terminal KDEL tetrapeptide which has been found in other lumenal proteins of the
      endoplasmic reticulum. The 3' untranslated region contains a polyadenylation and
      an adenylation control element (ACE) as well as a putative mRNA instability
      sequence. The Xenopus BiP amino acid sequence displayed high identity with BiP
      from other vertebrates including chicken (91.3%), rat (90.7%), and human (89.9%).
      Northern hybridization analysis demonstrated that BiP mRNA was present
      constitutively in the Xenopus A6 kidney epithelial cell line and that BiP mRNA
      levels could be enhanced by treatment of the cells with galactose-free media, 2
      deoxyglucose, 2-deoxygalactose, glucosamine, tunicamycin, heat shock,
      dithiothreitol, and the calcium ionophore, A23187. Finally, while BiP mRNA was
      detected in all of the adult tissues examined, the relative level of BiP mRNA
      differed dramatically between organs. For example, relatively high levels of BiP
      mRNA were detected in liver with moderate levels in testis, ovary and heart and
      reduced levels in eye and muscle tissue.

PMID- 9159888
TI  - Ketone body metabolism in the Carp Cyprinus carpio: biochemical and 1H NMR
      spectroscopical analysis.
AB  - In fed and starved carp, Cyprinus carpio, ketone body metabolism and those
      metabolic and endocrine factors that are known to induce ketogenesis in starving
      mammals were investigated. Acetoacetate was detected in plasma and liver of both
      fed and starved carp. We could not detect 3-hydroxybutyrate, neither by 1H-NMR
      spectroscopy nor by spectrophotometric assay, in spite of low activities of
      hepatic 3-hydroxybutyrate dehydrogenase. Starvation of carp did not create
      metabolic conditions that would favor ketone body synthesis: Mobilization and
      hepatic catabolism of fatty acids were only moderately enhanced, the rate of
      gluconeogenesis was not elevated, and glucagon levels as well as the
      glucagon/insulin-ratio remained stable or declined. Therefore, the discrepancy in
      the effect of food deprivation on mammalian and teleostean ketogenesis appears to
      be caused not by the absence of the ketogenic pathway from teleosts but by major
      differences between mammals and fish in their metabolic response to starvation.

PMID- 9159889
TI  - Biosynthesis of docosahexaenoic acid in trout hepatocytes proceeds via 24-carbon
      intermediates.
AB  - The role of 24:5n-3 and 24:6n-3 as intermediate in the formation of 22:6n-3 in
      trout liver was examined. Microsomes prepared from trout liver converted [1-14C]
      eicosapentaenoic acid (20:5n-3) to 24: 5n-3 and 24:6n-3 but not docosahexaenoic
      acid (22:6n-3). The radiolabeled 24:5n-3 and 24:6n-3 were isolated from the
      microsomal incubations by argentation chromatography and used as substrates in
      incubations with hepatocytes isolated from trout liver. Both 14C-labelled 24:6n-3
      and 22:6n-3-were produced by hepatocytes incubated with radiolabelled 24:5n-3.
      When hepatocytes were incubated with radiolabelled 24:6n-3, the amount of
      radioactivity recovered in 22:6n-3 over 6 hr increased in direct relation to the
      decrease observed in the amount of radioactivity recovered in 24:6n-3. The
      results suggest that the formation of 22:6n-3 in trout liver does not involve
      delta 4 desaturation of 22:5n-3 but rather proceeds via the delta 6 desaturation
      of 24:5n-3 with the subsequent chain shortening of the 24:6n-3 produced.

PMID- 9159890
TI  - Seasonal levels of reproductive hormones and their relationship to the antler
      cycle of male and female reindeer (Rangifer tarandus).
AB  - Seasonal levels of LH, FSH, testosterone (T), estradiol, progesterone (P), and
      prolactin (PRL) were determined in the plasma of five adult bulls, and five
      barren and four pregnant cows of Alaskan reindeer (Rangifer tarandus), which were
      sampled every 3 weeks for 54 weeks. The male reproductive axis was sequentially
      activated; LH peaked in May-June (2 ng/ml), FSH in June (51 ng/ml), and T in
      September (11.8 ng/ml). LH levels in females reached a maximum in both groups at
      the end of August (the beginning of the rut). Seasonal variation in FSH was
      minimal in pregnant cows, but exhibited one elevation (41 ng/ml) in barren ones
      in November. T levels in cows remained at barely detectable levels. The decrease
      of T values observed in both groups in December and March was not significant.
      PRL peaked in May in cows (135 ng/ml pregnant, 140 ng/ml non-pregnant) and in
      June in bulls (92 ng/ml). Estradiol was highest in bulls in the rut (August), in
      non-pregnant cows in January and in pregnant cows in April, shortly before
      parturition. P levels in the pregnant cows rose from September and peaked (9
      ng/ml) shortly before parturition in April. In the non-pregnant females P values
      increased and decreased several times before peaking (5 ng/ml) in March. In the
      males, the variation of T and estradiol levels correlated relatively well with
      the antler cycle but in the females the variation of neither estradiol,
      progesterone nor T appeared to be related to mineralization or casting of
      antlers.

PMID- 9159891
TI  - Environmental specimen banking in Germany--present state and further challenges.
AB  - The program of the German Environmental Specimen Bank has been expanded recently
      and its current status is briefly described. Selected results which have been
      obtained during the long term permanent operation of this project since 1985 are
      presented. Moreover, further aspects of environmental data evaluation and
      assessment are discussed.

PMID- 9159892
TI  - Specimen banking of marine organisms in the United States: current status and
      long-term prospective.
AB  - A major part of the activities conducted over the last decade by the National
      Biomonitoring Specimen Bank (NBSB) has involved the archival of marine specimens
      collected by ongoing environmental monitoring programs. These archived specimens
      include bivalves, marine sediments, and fish tissues collected by the National
      Status and Trends and the Exxon Valdez Oil Spill Damage Assessment programs, and
      marine mammal tissues collected by the Marine Mammal Health and Stranding,
      Response Program and the Alaska Marine Mammal Tissue Archival Project. In
      addition to supporting these programs, the specimens have been used to
      investigate circumpolar patterns of chlorinated hydrocarbon concentrations,
      genetic separation of marine animal stocks, baseline levels of essential and
      nonessential elements in marine mammals, and the potential risk to human
      consumers in the Arctic from anthropogenic contaminants found in local
      subsistence foods. The NBSB specimens represent a resource that has the potential
      for addressing future issues of marine environmental quality and ecosystem
      changes through retrospective analysis; however, an ecosystem-based food web
      approach would maximize this potential. The current status of the NBSB activities
      related to the banking of marine organisms is presented and discussed, the long
      term prospective of these activities is presented, and the importance of an
      ecosystem-based food web monitoring approach to the value of specimen banking is
      discussed.

PMID- 9159893
TI  - Specimen banking at National Institute for Environmental Studies, Japan.
AB  - The National Institute for Environmental Studies (NIES) in Japan has had more
      than fifteen years practical experience in specimen banking. Stored specimens are
      used for the assessment of long-term trends of pollutants. The use of new
      analytical techniques facilitates the finding of the pollutants of the past.

PMID- 9159894
TI  - The Great Lakes Fisheries Specimen Bank: a Canadian perspective in environmental
      specimen banking.
AB  - Since 1977 the Canadian Department of Fisheries and Oceans (DFO) has maintained a
      specimen bank for retrospective chemical analyses. The Great Lakes Fisheries
      Specimen Bank (GLFSB) is a complementary activity to the department's ongoing
      Great Lakes Contaminants Surveillance Program that has annually, since 1977,
      monitored levels of metals and organochlorines in aquatic biota throughout the
      Canadian Great Lakes. Past activities have focused on defining the effects of
      long-term frozen storage on the integrity of organochlorine residues in archived
      biological tissues. Archived samples have been reanalyzed for total PCBs, PCB
      congeners including co-planar PCBs, dioxin and furan isomers, and 22 toxaphene
      congeners. More recently, archived samples of predatory fish have been analyzed
      for stable isotopes of nitrogen (delta 15N) and carbon (delta 13C), as indicators
      of historical changes in food web dynamics. A catalogue or user-guide has
      recently been completed describing all information associated with samples stored
      in the GLFSB.

PMID- 9159895
TI  - The relationship between the Canadian Wildlife Service Specimen Bank and the
      Wildlife Toxicology Program: the effect on specimen collection.
AB  - A general description of the Canadian Wildlife Service Specimen Bank is given.
      Eighty percent of the 55000 specimens stored are wild bird tissues. Tissues are
      collected as part of the Wildlife Toxicology Program and subjected to chemical
      and biochemical testing. Tissues are stored at various freezing temperatures i.e.
      -40 degrees C, -85 degrees C or in the gaseous phase over liquid nitrogen,
      depending on the intended analytical work to be done.

PMID- 9159896
TI  - Environmental specimen banking of nationwide biomonitoring samples in Finland.
AB  - An environmental specimen bank was built in 1994 by the Finnish Forest Research
      Institute. The main material stored is moss samples collected from the permanent
      nationwide sampling network every five years since 1985 for both national and
      international heavy metal surveys. Correspondingly there are nationwide
      biomonitoring samples of epiphytic lichen, pine bark and humus for surveying
      atmospheric heavy metal deposition. The bank is also storage of forest litter
      collected from 1960's onwards. This large material, tens of thousands of sorted
      samples, is valuable for indicating environmental changes of the forest
      ecosystem.

PMID- 9159897
TI  - Biological and environmental specimen banking at the Centers for Disease Control
      and Prevention.
AB  - Scientific programs at the Centers for Disease Control and Prevention encompass
      diverse public health interests. These programs include investigations of newly
      emerging infectious diseases, assessments of chronic disease risk factors, and
      evaluations of environmental health hazards. Since the early 1960s, CDC has
      maintained a specimen bank to retain aliquots of biological specimens collected
      from a variety of epidemiologic investigations as well as from the National
      Health and Nutrition Examination Surveys (NHANES). CDC's National Institute of
      Occupational Safety and Health (NIOSH) also maintains a repository of
      environmental materials from its investigations. To extend its repository
      capabilities more effectively, CDC has begun developing a new facility that, when
      finished, will meet CDC's storage needs for both biological and environmental
      specimens. A highly complex but very flexible information management system for
      this project, enabling the storage of data related to studies for which these
      specimens were originally collected, has already been completed. Proper specimen
      collection, archiving, and short- or long-term storage of specimens for
      environmental health-related analyses is critical for the work of the staff of
      the Division of Environmental Health Laboratory Sciences, National Center for
      Environmental Health, who perform a variety of biochemical analyses on biological
      specimens, including quantitation of dioxins, furans, coplanar PCBs, pesticides,
      volatile organic compounds, metabolites, essential and toxic trace elements,
      vitamins, and lipids, and also conduct genetic screening. Information regarding
      these analytes is an essential part of the CDC Repository Database.

PMID- 9159898
TI  - Specimen banking--a planning in advance.
AB  - The future value and usefulness of a Specimen Banking Programme is dependent on
      the way we select the material to be saved and the way we save it. If the
      material consists of non-representative samples or samples from which we cannot
      produce a set of analytical chemical data that allows us to make a proper
      statistical analysis, then the data merely provides us with anecdotal
      information. Experience as well as studies of large data sets have taught us that
      poor research material gives us poor understanding and knowledge. We know in
      advance that some questions will be important in the future. Of these, spatial
      and temporal changes in environmental contamination are high on the list. What
      priorities should we set and what kind of selection criteria should we use to
      create useful collections in the specimen banks? This paper will discuss some of
      the qualities samples must possess if they are to be included in a specimen bank.

PMID- 9159899
TI  - Environmental specimen banking in the Czech Republic: a pilot study.
AB  - In recognition of the importance of environmental specimen banking (ESB) as an
      important component of the described ongoing real-time environmental and health
      related monitoring programmes, a proposal for a planned ESB pilot study in the
      Czech Republic is presented. Selection of biomonitors, analytes, sampling
      techniques and sites is discussed, especially with regard to the possible
      harmonization with ESB already operational abroad. Availability of validated
      analytical techniques for determination of up to 30 elements using nuclear and
      spectroscopic techniques, including speciation of several metals, and of the most
      important organic pollutants employing various chromatographic techniques in
      biological and environmental samples is demonstrated.

PMID- 9159900
TI  - Standard species from Poland for environmental specimen bank.
AB  - The Environmental Specimen Bank has proposed a list of matrices recommended for
      collection from terrestrial and marine areas as well as from inland waterbodies.
      There have been taken into consideration the most common and available species,
      chiefly in western Europe. Poland is making ready for co-operation with ESB to
      gather samples within the country and must consider a number of regional
      differences resulting from among others geographical distinction (another
      quantity of populations, spatial distribution etc.). There are also different
      legislative regulations with respect to protection of certain species. The
      authors have selected some species from the list of ESB and proposed in certain
      cases substitutional matrices.

PMID- 9159901
TI  - Concepts of marine specimen banking.
AB  - For more than a decade environmental specimen banking (ESB) has been an
      established approach for monitoring and retrospective environmental survey
      purposes in a number of developed countries. Specimen banking is carried out on
      regional or national scales for various environmental materials. The ecological
      or problem-oriented approach, as pursued e.g. in Germany or USA has the
      advantages of a restricted survey and a clear political mandate. Environmental
      problems, however, are by no means national or regional issues, since the
      diversity and dispersion of hazardous substances make environmental monitoring
      clearly a global affair. The structuring of our environment suggests that banking
      should not be limited by national boundaries, but rather be based on eco
      systematic principles. Such distinct banking efforts should be devoted to the
      monitoring of physico-chemical aspects of climatic change and air pollution, soil
      quality, and aquatic monitoring on a world-wide scale. As some experience already
      exists with specialized banking programs for marine samples, such as the National
      Marine Mammal Tissue Bank or the Mussel Watch Program in the United States, an
      international marine specimen bank, based on principles of national ESB's, is
      advocated to be established in due time. Following the recommendations of the
      1992 Rio 'Earth Summit' to pursue sustainable development strategies, such an
      establishment could strongly facilitate efforts concerning pollution control and
      mitigation, overexploitation and mining of ocean resources on a regional or
      global scale.

PMID- 9159902
TI  - Stability of cytochrome P4501A-associated enzyme activity in cryogenically stored
      teleost liver samples.
AB  - Induction of cytochrome P4501A (CYP1A), more specifically the associated enzyme
      activity aryl hydrocarbon hydroxylase (AHH), has been shown to be one of the most
      sensitive measures of exposure of vertebrate animals to a range of organic
      chemical contaminants. However, in order to reliably use this biochemical method
      for analyzing archived samples, the stability of the enzyme activity in storage
      must be ascertained. Stability of AHH activity was determined for both tissue
      sections and subcellular fractions of liver collected from English sole
      (Pleuronectes vetulus), and held in cryogenic storage for up to 24 months. Our
      overall recommendations for sample collection, handling, storage, and assay are
      given.

PMID- 9159903
TI  - Particle size distribution in ground biological samples.
AB  - Modern trace and retrospective analysis of Environmental Specimen Bank (ESB)
      samples require surplus material prepared and characterized as reference
      materials. Before the biological samples could be analyzed and stored for long
      periods at cryogenic temperatures, the materials have to be pre-crushed. As a
      second step, a milling and homogenization procedure has to follow. For this
      preparation, a grinding device is cooled with liquid nitrogen to a temperature of
      -190 degrees C. It is a significant condition for homogeneous samples that at
      least 90% of the particles should be smaller than 200 microns. In the German ESB
      the particle size distribution of the processed material is determined by means
      of a laser particle sizer. The decrease of particle sizes of deer liver and bream
      muscles after different grinding procedures as well as the consequences of
      ultrasonic treatment of the sample before particle size measurements have been
      investigated.

PMID- 9159904
TI  - Mussels and algae as bioindicators for long-term tendencies of element pollution
      in marine ecosystems.
AB  - Results of more than ten years of experience in the determination of metals in
      mussels and algae collected in the North Sea and the Baltic Sea are presented.
      The various elements determined here are Hg, As, Se, Cd, Pb, Cu, Na, K, S, P, Zn,
      Mn, Fe, Sr, Ca, Ba, Mg, Tl, Ni, Co using techniques such as cold vapor AAS, INAA,
      hydride generation AAS, electrothermal AAS, ICP-AES, IDMS and stripping
      voltammetry. The results indicate the occurrence of three groups of elements with
      respect to long-term tendencies of their concentrations. In the first group, the
      concentrations in both mussels and algae varied in the same manner; in the second
      group no change was observed in either matrix while in the third group, the
      concentrations of elements changed in an opposite manner.

PMID- 9159905
TI  - The Swedish Environmental Specimen Bank--application in trend monitoring of
      mercury and some organohalogenated compounds.
AB  - The Environmental Specimen Bank (ESB) at the Swedish Museum of Natural History,
      Stockholm, constitutes a base for ecotoxicological research as well as for
      spatial and trend monitoring of contaminants in Swedish fauna. Since the 1960s,
      tissue samples from more than 150000 organisms have been collected from different
      groups of animals, habitats and types of landscape. Samples from the ESB have
      been utilized for retrospective studies of trace elements, organohalogenated
      compounds and radionuclides. Among many matrices utilized, eggs of guillemot
      (Uria aalge) have proven to be an appropriate matrix for assessment of the
      contamination of the Baltic Sea. Results from time trend studies based on this
      material showing trends in concentrations of DDT, PCB, PCDD/F, and mercury are
      presented in this paper.

PMID- 9159906
TI  - Concentrations of chlorinated hydrocarbons and trace elements in marine mammal
      tissues archived in the U.S. National Biomonitoring Specimen Bank.
AB  - The U.S. National Biomonitoring Specimen Bank (NBSB) provides for the long term
      storage of well documented and preserved specimens representing several types of
      environmental matrices. A major part of this inventory consists of marine mammal
      tissues (e.g., blubber, liver, kidney, and muscle). Within the NBSB selected
      specimens are periodically analyzed for chlorinated hydrocarbons and trace
      elements. Although only 20% of the 560 marine mammal specimens in the NBSB have
      been analyzed, the database is of value in evaluating the stability of analytes
      and sample degradation during storage, for comparing with results from samples
      collected in the future for long-term monitoring, and for comparing with
      analytical results from other laboratories on samples collected at the same time
      for monitoring purposes. The NBSB analytical database contains results for 37
      elements, many of which are not analyzed routinely by conventional analytical
      techniques used in monitoring programs, and the following organic compounds:
      selected PCB congeners. DDT compounds, alpha- and gamma-HCH, HCB, heptachlor
      epoxide, oxychlordane, cis-chlordane, trans-chlordane, cis-nonachlor, trans
      nonachlor, and dieldrin in 9 marine mammal species: northern fur seal
      (Callorhinus ursinus), ringed seal (Phoca hispida), spotted seal (P. largha),
      bearded seal (Erignathus barbatus), pilot whale (Globicephala melas), harbor
      porpoise (Phocoena phocoena), white-sided dolphin (Lagenorhynchus acutus), beluga
      whale (Delphinapterus leucas), and bowhead whale (Balaena mysticetus). Analyses
      of beluga whale blubber for toxaphene and additional chlorinated hydrocarbons are
      obtained through collaboration with the Department of Fisheries and Oceans
      Canada.

PMID- 9159907
TI  - Long-term decline of atmospheric and marine pollution by polycyclic aromatic
      hydrocarbons (PAHS) in Germany.
AB  - Concentrations of benzo[a]pyrene and benzo[e]pyrene in the atmosphere as markers
      for the class of PAHs decreased by about 70% within one decade in clean air as
      well as in industrially polluted areas of Germany when measured with passive
      samplers (spruce sprouts, poplar and beech leaves). The same trend has been found
      for East-Germany during 1991-1995. Mussels (Mytilus edulis) were found to
      accumulate PAHs from the aquatic environment and exhibited a seasonal periodicity
      of the PAH concentration. After an initial decline from 1985 to 1990, the PAH
      concentration remained constant until 1995 in the North Sea area investigated.

PMID- 9159908
TI  - Organochlorine contaminants in blubber of four seal species: integrating
      biomonitoring and specimen banking.
AB  - Blubber samples from four Alaska seal species (bearded seal, Erignathus barbatus,
      harbor seal, Phoca vitulina, northern fur seal, Callorhinus ursinus, ringed seal,
      P. hispida) were collected for inclusion in the US National Biomonitoring
      Specimen Bank, as well as for immediate analysis as part of the contaminant
      monitoring component of the US National Marine Fisheries Service's Marine Mammal
      Health and Stranding Response Program. The blubber samples were analyzed for
      organochlorine (OC) contaminants (e.g., PCB congeners, pesticides, DDTs). Results
      for bearded and ringed seals from the Alaska Arctic revealed low blubber
      concentrations of OC contaminants. Harbor seals from Prince William Sound. Gulf
      of Alaska, had somewhat higher blubber concentrations of OC contaminants. In
      contrast, northern fur seals sampled from the Pribilof Islands had blubber
      concentrations of certain OC contaminants that were about an order of magnitude
      higher than those found in the other seal species. Differences in contaminant
      concentrations among the Alaska seals may be explained by differences in feeding
      habits and migratory patterns, age or gender did not appear to account for the
      differences observed. The highest concentrations of OCs were found in harbor
      seals stranded along the northwestern US mainland, which is consistent with
      higher concentrations of anthropogenic contaminants being found in urban coastal
      areas than in more remote Arctic environments. The integration of real-time
      contaminant monitoring with specimen banking provides important baseline data
      that can be used to plan and manage banking activities. This includes identifying
      appropriate specimens that are useful in assessing temporal trends and increasing
      the utility of the banked samples in assessing chemical contaminant accumulation
      and relationships to biological effects.

PMID- 9159909
TI  - Eel-pout (Zoarces viviparus L.) as a marine bioindicator.
AB  - Several elements and metal species were analyzed in eel-pout or viviparous blenny
      (Zoarces viviparus). The analytical data demonstrate that fish muscle is a
      suitable bioindicator for mercury (Hg) and arsenic (As). About 90% of the total
      Hg content is present in the fish muscle in the form of methyl mercury. Due to
      higher concentration levels, the liver is more useful for monitoring Pb and TI.
      No biomagnification of some trace elements, such as Cd, Ni or Co, were observed
      in eel-pout. More information is necessary to decide about the use of eel-pout
      for long-time monitoring programs.

PMID- 9159910
TI  - Environmental monitoring and banking of marine pollutants by using common
      mussels.
AB  - Since 1985 the common mussel Mytulis edulis has been collected, characterized and
      stored within the framework of the German Environmental Specimen Bank program.
      Selected results about the determination of various pollutants such as heavy
      metals, polycyclic aromatic hydrocarbons and chlorinated hydrocarbons are
      presented. Particular emphasis is given to the comparison of seasonal variations
      with respect to different environmental contaminants and their correlations
      depending on sampling location and time.

PMID- 9159911
TI  - PCDD/F and other chlorinated hydrocarbons in matrices of the Federal
      Environmental Specimen Bank.
AB  - Minimisation of PCDD/F emissions leads to a decreasing burden of the bioindicator
      herring gull egg in the last few years. Unfortunately, the river Elbe sediment is
      highly polluted with PCDD/F. The temporal burden of the sediment is fluctuating.
      Due to the different intake and type of feed differences of the PCDD/F burden of
      herring gull eggs and pigeon eggs can be explained. Constant ratios between fat
      related tissue data of liver and muscle are found and can be used for predictive
      purposes.

PMID- 9159912
TI  - Chemical contaminants in harbor porpoise (Phocoena phocoena) from the north
      Atlantic coast: tissue concentrations and intra- and inter-organ distribution.
AB  - Concentrations of chlorinated hydrocarbons (CHs), such as polychlorinated
      biphenyls (PCBs), were measured in subsamples taken from different anatomical
      locations of blubber and liver of three apparently healthy harbor porpoises
      (Phocoena phocoena) incidentally caught in a gill-net fishery along the northwest
      Atlantic coast; selected elements (e.g., mercury) were measured in subsamples of
      liver. The vertical distribution (skin to muscle) of contaminants within blubber
      was also determined. Additionally, the concentrations of CHs and elements were
      determined in individual samples of brain, lung, kidney, and testis to assess how
      the disposition of toxic chemicals may be dependent on the physiological
      characteristics of a specific organ. Statistical analyses of the results showed
      that the anatomical location of the blubber or liver sample had no significant
      effect on concentrations of either CHs in blubber and liver, or of selected
      elements in liver. However, there were statistical differences between strata of
      blubber (skin to muscle) for the concentrations of CHs. As expected, the results
      showed that the CH concentrations, based on wet weight, were considerably higher
      in the blubber than in the other tissues; however, the concentrations of CHs in
      the different tissues were more comparable when values were based on total lipid
      weight with the exception of the brain where lipid normalized concentrations were
      lower than in all other tissues: This low relative accumulation of lipophilic
      contaminants in the brain tissue may be due to the presence of the blood-brain
      barrier, or due to a lower proportion of neutral lipids, such as triglycerides,
      as analysis for percent lipid and for the proportion of specific lipid classes
      showed.

PMID- 9159913
TI  - Levels of chlorinated hydrocarbons (CHC) in breams (Abramis brama) from the river
      Elbe (a contribution to the Federal Environmental Specimen Bank).
AB  - The levels of chlorinated hydrocarbon (CHC) contaminants in muscle and liver
      tissues of bream (Abramis brama) along the river Elbe were monitored during 1991,
      1993 and 1994. Especially fish from the eastern sampling sites (Prossen, Dresden)
      has been heavily contaminated by HCB, OCS, DDT-metabolites and PCBs. In 1991, the
      concentrations of OCS, DDE and PCBs decreased significantly by 65, 65 and 51%,
      respectively, between Dresden and Vockerode and did not change very much from
      Vockerode downstream to Cumlosen. Elevated HCH levels were found in Aken, Barby
      and Heinrichsberg. An increasing temporal pattern during this period was found
      for HCB, OCS and DDE in Prossen.

PMID- 9159914
TI  - Elemental concentrations in medicinally important leafy materials.
AB  - Concentrations of elements, especially of trace elements toxic as well as non
      toxic in biological materials show a high degree of biological, seasonal and
      spatial variability. These factors should be taken care of while sampling.
      Samples, even though collected at a great distance of time and space, should be
      representative and quantitatively comparable which is important for
      biomonitoring. Reference Materials (RM's) from biological materials such as
      leaves acquire importance in Analytical Quality Assurance work. A knowledge of
      element concentrations in highly consumed leafy samples is of interest. A large
      number of medicinally important leafy samples (50) have been analysed for
      elemental concentrations such as Zn, Cu, Ni, Co, Pb, As, Se, K, Cr, Na, P, S, Fe,
      Ca Mg, Mn and Fe. The concentrations of macro nutrients such as Ca, P, Mg, K, Fe
      and S range from 9.62 to 4174, 1.00-8.630, 3.53-35.50, 12.04-56.28, 0.111-3.845
      g/kg and 1.124-5.843 mg/kg, of micro nutrients such as Cr, Co, Cu, Mn, Na and Zn
      range from 0.360-8.630, 0.050-3.470, 17.60-57.30, 10.5-81.6, 1.47-27.10 and 10.06
      145.6 mg/kg whereas those of trace metals such as Pb, Cd, Ni, As and Se range
      from 1.19-16.30, 0.0036-0.453, 1.23-19.60, 0.12-7.360 and 0.654-3.50 mg/kg
      respectively. Influence of sampling parameters such as season and spatial
      variations has been assessed and the results are interpreted. Spatial variation
      and seasonal variation are observed to be statistically significant for Cu, Zn
      and Mn. Preparation of Secondary Reference Materials (SRM's) from the samples
      analysed is explored. Nutritive values of the leaves and intercorrelation between
      the metals are also discussed.

PMID- 9159915
TI  - Wet deposition in Germany: long-term trends and the contribution of heavy metals.
AB  - As part of the program of the German Environmental Specimen Bank (ESB),
      precipitation is sampled on a weekly basis from eight sites in different
      ecosystems throughout Germany. The samples are analyzed for Na+, NH4+, K+, Mg2+,
      Ca2+, Cl-, NO3-, and SO4(2-) using ion chromatography with conductometrie
      detection Mn, Co, Ni, Cu, Zn, Cd, Pb, and Tl are determined by ICP-MS. In
      addition, pH and conductivity of the samples are measured. In this paper, the
      weekly and annual deposition in 1994 is compared for the different sampling sites
      and with literature data.

PMID- 9159916
TI  - The lessons of Bhopal [toxic] MIC gas disaster scope for expanding global
      biomonitoring and environmental specimen banking.
AB  - Bhopal Toxic gas tragedy represents one of the worst chemical accidents of the
      world. Autopsy and toxicological studies, apart from presenting evidence of acute
      and even chronic cyanide toxicity, provided a unique example of the incriminated
      chemical being traced to the bodies of the victims. The entry of methyl
      isocyanate (MIC) into the blood stream was established by the presence of
      carbamoylated end-terminal amino acids of haemoglobin and other tissue proteins.
      The presence of MIC trimer and a few other identified as well as unidentified
      tank residue constituents in the blood and viscera further established a close
      nexus of the products of pyrolysis of MIC in the aerosol inhaled by the victims.
      The Bhopal studies exemplify the scope for biological monitoring (BM) and
      environmental specimen banking (ESB) in chemical accidents as part of the global
      efforts.

PMID- 9159917
TI  - What a maleless group can tell us about the constraints on female transfer in
      Thomas's langurs (Presbytis thomasi).
AB  - During a long-term study of wild Thomas's langurs (Presbytis thomasi), the adult
      male of one of the bisexual study groups, group M, suddenly disappeared. Just
      after the adult male's disappearance, the females of group M actively avoided
      other groups and sometimes formed subgroups. Infants were attacked by extra-group
      males and 1 infant disappeared. After about 2 months, the females initiated
      affiliative interactions with males of neighbouring groups. Aggressive
      interactions between females of group M and females of other groups were also
      observed. Females of group M did not leave their home range in spite of efforts
      by adult males to lead them away. After about 4.5 months, a former all-male band
      member joined group M. The coincidences of this case suggest that increased
      infanticide risk, increased food competition, loss of knowledge of the home range
      and loss of established social relationships could be important constraints on
      female transfer. A comparison with 5 other studies of 1-male groups in which the
      adult male disappeared showed that proximate factors, such as the presence of
      infants, the size of neighbouring groups and the presence of extra-group males,
      influence female decisions.

PMID- 9159918
TI  - Relative position and extent of the nasal and orbital openings in Gorilla, Pan
      and the human species from the study of their areas and centres of area.
AB  - In order to quantify the relative position and extent of the nasal and orbital
      openings in hominoid primates, a new methodology based on image analysis was
      developed and applied to a series of 134 hominoid skulls (52 Gorilla gorilla; 30
      Pan troglodytes; 44 Homo sapiens, and, as comparison material, 8 Pongo pygmaeus).
      The areas and the centres of area of the orbital and nasal openings were
      determined automatically. The orbitonasal triangle connecting these three centres
      of area was then constructed. This triangle was used to quantify the elongation
      of the face. It was most elongated in gorilla, shortest in the human species and
      intermediate in Pan; the elongation in Pongo was close to that in Gorilla. The
      proportions of the areas of the orbital and nasal openings in the face were
      related to the extent of the bony structures of the midface and were thus used to
      quantify the facial robustness. A robust face was demonstrated in Gorilla, but a
      gracile face in the human species. Robusticity in Pan was intermediate.

PMID- 9159919
TI  - Atelines, apes and wrist joints.

PMID- 9159920
TI  - Methods for X-ray microanalysis of epidermis: the effect of local anaesthesia.
AB  - The effect of local anaesthesia on the elemental content of cells in human
      epidermis was studied by electron probe X-ray microanalysis. Local anaesthesia
      with lidocaine was given by intracutaneous injection within 1 min prior to taking
      a skin biopsy. Biopsies taken without local anaesthesia were used as controls.
      Lidocaine with or without adrenaline caused a significant increase in the
      concentrations of Na and Cl, and a decrease in the concentration of K in the
      cells of the stratum basale and the stratum spinosum, compared with the control
      samples. The presence of adrenalin in the anaesthetic did not change the effect
      of lidocaine. The effects of local anaesthesia have to be considered in planning
      and interpretation of clinical applications of X-ray microanalysis.

PMID- 9159922
TI  - Generalized region growing operator with optimal scanning: application to
      segmentation of breast cancer images.
AB  - Segmentation of medical images is a complex problem owing to the large variety of
      their characteristics. In the automated analysis of breast cancers, two image
      classes may be distinguished according to whether one considers the
      quantification of DNA (grey level images of isolated nuclei) or the detection of
      immunohistochemical staining (colour images of histological sections). The study
      of these image classes generally involves the use of largely different image
      processing techniques. We therefore propose a new algorithm derived from the
      watershed transformation enabling us to solve these two segmentation problems
      with the same general approach. We then present visual and quantitative results
      to validate our method.

PMID- 9159921
TI  - Calcium in secretory vesicles of neurohypophysial nerve endings: quantitative
      comparison by X-ray microanalysis of cryosectioned and freeze-substituted
      specimens.
AB  - The calcium content of individual secretory vesicles in rat neurohypophysial
      nerve endings was measured by quantitative electron probe X-ray microanalysis.
      Directly frozen control and potassium-depolarized isolated endings were analysed
      using two presumably equivalent preparative techniques: (1) freeze-substitution
      in presence of oxalic acid followed by sectioning of resin-embedded pellets; or
      (2) direct cryosectioning of the frozen pellets followed by freeze-drying in the
      column of the microscope. In the pellets of stimulated endings, both approaches
      revealed an increase in the calcium content of neurosecretory vesicles. This
      increase was statistically more significant in the specimens prepared by
      cryosectioning, probably because in this case the contribution of 'dead' nerve
      endings could be eliminated on the basis of excessive cytoplasmic sodium and
      chloride. The results demonstrate that an increase in cytosolic calcium can lead
      to an increase in intravesicular calcium, and that when this occurs, it occurs
      within a subpopulation of vesicles in a given nerve ending. In addition, measured
      intravesicular calcium was dispersed over a wide range of concentrations, as
      predicted by the hypothesis of intravesicular calcium priming. When the vesicular
      calcium content was averaged per nerve ending, a relatively wide distribution of
      concentrations was again observed, indicating that some nerve endings respond
      more strongly to the stimulation than others.

PMID- 9159923
TI  - Drying cells for SEM, AFM and TEM by hexamethyldisilazane: a study on hepatic
      endothelial cells.
AB  - Critical point drying (CPD) is a common method of drying biological specimens for
      scanning electron microscopy (SEM). Drying by evaporation of hexamethyldisilazane
      (HMDS) has been described as a good alternative. This method, however, is
      infrequently used. Therefore, we reassessed HMDS drying. Cultured rat hepatic
      sinusoidal endothelial cells (LEC), possessing fragile fenestrae and sieve
      plates, were subjected to CPD and HMDS drying and evaluated in the scanning
      electron microscope, atomic force microscope (AFM) and transmission electron
      microscope (TEM). We observed no differences between the two methods regarding
      cellular ultrastructure. In contrast with CPD, HMDS drying takes only a few
      minutes, less effort, low costs for chemicals and requires no equipment. We
      conclude that HMDS-dried specimens have equal quality to CPD ones. Furthermore,
      the method also proved useful for drying whole-mount cells for TEM and AFM.

PMID- 9159924
TI  - Variation in the ribosomal internal transcribed spacers and 5.8S rDNA among five
      species of Acropora (Cnidaria; Scleractinia): patterns of variation consistent
      with reticulate evolution.
AB  - The ITS sequences of Acropora spp. are the shortest so far identified in any
      metazoan and are among the shortest seen in eukaryotes; ITS1 was 70-80 bases, and
      ITS2 was 100-112 bases. The ITS sequences were also highly variable, but base
      composition and secondary structure prediction indicate that divergent sequence
      variants are unlikely to be pseudogenes. The pattern of variation was unusual in
      several other respects: (1) two distinct ITS2 types were detected in both A.
      hyacinthus and A. cytherea, species known to hybridize in vitro with high success
      rates, and a putative intermediate ITS2 form was also detected in A. cytherea;
      (2) A. valida was found to contain highly (29%) diverged ITS1 variants; and (3)
      A. longicyathus contained two distinct 5.8S rDNA types. These data are consistent
      with a reticulate evolutionary history for the genus Acropora.

PMID- 9159925
TI  - The partition matrix: exploring variable phylogenetic signals along nucleotide
      sequence alignments.
AB  - The partition matrix is a graphical tool for comparative analysis of nucleotide
      sequences following alignment. It is particularly useful for investigating the
      divergent phylogenies of sequence regions undergoing reticulate evolution. A
      partition matrix is generated by determining the consistency of the
      parsimoniously informative sites in a set of aligned sequences with the binary
      partitions inferred from the sequences. Since the linear order of sites is
      maintained, the matrix can be used to assess whether the distribution of sites
      either supporting or conflicting with particular partitions changes along the
      length of the alignment. The usefulness of the matrix in allowing visual
      identification of differences in evolutionary history among regions depends on
      the order in which partitions are shown; several suitable ordering schemes are
      proposed. We demonstrate the use of the partition matrix in interpreting the
      evolution of the pseudoautosomal boundary region on the sex chromosome of
      catarrhine primates. Its routine use should help to avoid attempts to derive
      single phylogenies from sequences whose evolution has been reticulate and to
      identify the gene conversion or recombination events underlying the reticulation.
      The method is relatively fast. It is exploratory, and it can form the basis for
      more formal analysis, which we discuss.

PMID- 9159926
TI  - Are the Platyhelminthes a monophyletic primitive group? An assessment using 18S
      rDNA sequences.
AB  - In most zoological textbooks, Platyhelminthes are depicted as an early-emerging
      clade forming the likely sister group of all the other Bilateria. Other
      phylogenetic proposals see them either as the sister group of most of the
      Protostomia or as a group derived from protostome coelomate ancestors by
      progenesis. The main difficulty in their correct phylogenetic placing is the lack
      of convincing synapomorphies for all Platyhelminthes, which may indicate that
      they are polyphyletic. Moreover, their internal phylogenetic relationships are
      still uncertain. To test these hypotheses, new complete 18S rDNA sequences from
      13 species of "Turbellaria" have been obtained and compared to published
      sequences of 2 other "Turbellaria," 3 species of parasitic Platyhelminthes, and
      several diploblastic and deuterostome and protostome triploblastics. Maximum
      parsimony, maximum-likelihood, and neighbor-joining methods were used to infer
      their phylogeny. The results show the order Catenulida to form an independent
      early-branching clade and emerge as a potential sister group of the rest of the
      Bilateria, while the rest of Platyhelminthes (Rhabditophora), which includes the
      parasites, form a clear monophyletic group closely related to the protostomes.
      The order Acoela, morphologically considered as candidates to be ancestral, are
      shown to be fast-clock organisms for the 18S rDNA gene. Hence, long-branching of
      acoels and insufficient sampling of catenulids and acoels leave their position
      still unresolved and call for further studies. Within the Rhabditophora, our
      analyses suggest (1) a close relationship between orders Macrostomida and
      Polycladida, forming a clear sister group to the rest of orders; (2) that
      parasitic platyhelminthes appeared early in the evolution of the group and form a
      sister group to a still-unresolved clade made by Nemertodermatida,
      Lecithoepitheliata, Prolecithophora, Proseriata, Tricladida, and Rhabdocoela; and
      (3) that Seriata is paraphyletic.

PMID- 9159927
TI  - Extreme differences in rates of molecular evolution of foraminifera revealed by
      comparison of ribosomal DNA sequences and the fossil record.
AB  - Foraminifera have one of the best known fossil records among the unicellular
      eukaryotes. However, the origin and phylogenetic relationships of the extant
      foraminiferal lineages are poorly understood. To test the current paleontological
      hypotheses on evolution of foraminifera, we sequenced about 1,000 base pairs from
      the 3' end of the small subunit rRNA gene (SSU rDNA) in 22 species representing
      all major taxonomic groups. Phylogenies were derived using neighbor-joining,
      maximum-parsimony, and maximum-likelihood methods. All analyses confirm the
      monophyletic origin of foraminifera. Evolutionary relationships within
      foraminifera inferred from rDNA sequences, however, depend on the method of tree
      building and on the choice of analyzed sites. In particular, the position of
      planktonic foraminifera shows important variations. We have shown that these
      changes result from the extremely high rate of rDNA evolution in this group. By
      comparing the number of substitutions with the divergence times inferred from the
      fossil record, we have estimated that the rate of rDNA evolution in planktonic
      foraminifera is 50 to 100 times faster than in some benthic foraminifera. The use
      of the maximum-likelihood method and limitation of analyzed sites to the most
      conserved parts of the SSU rRNA molecule render molecular and paleontological
      data generally congruent.

PMID- 9159928
TI  - Fragmented and scrambled mitochondrial ribosomal RNA coding regions among green
      algae: a model for their origin and evolution.
AB  - Mitochondrial ribosomal RNA coding regions in the only three green algal taxa
      investigated to date are fundamentally different in that they are continuous in
      Prototheca wickerhamii, but highly fragmented and scrambled in Chlamydomonas
      reinhardtii and Chlamydomonas eugametos. To gain more insight into the mode of
      evolution of fragmented and scrambled mitochondrial ribosomal RNA (rRNA) genes
      within the green algal group, this work (1) provides additional information on
      fragmentation patterns of mitochondrial small- and large-subunit (SSU and LSU)
      rRNAs that strongly supports the concept of a gradual increase in the extent of
      discontinuity of mitochondrial rRNAs among chlorophycean green algae and (2)
      reports the first example of fragmented and scrambled mitochondrial LSU rRNA
      coding regions in a green algal taxon outside the Chlamydomonas group. The
      present study (1) suggests that the scrambling of the mitochondrial rRNA coding
      regions may have occurred early in the evolution of fragmented and scrambled
      mitochondrial rRNA genes within the chlorophycean green algal group, most likely
      in parallel with the fragmentation events, (2) proposes recombination as a
      possible mechanism involved in the evolution of these mitochondrial rRNA genes,
      and (3) presents a hypothetical pathway for converting continuous mitochondrial
      rRNA genes into the highly fragmented and scrambled rRNA coding regions of
      Chlamydomonas through a series of recombinatorial events between short repeated
      sequences.

PMID- 9159929
TI  - Intron open reading frames as mobile elements and evolution of a group I intron.
AB  - Group I introns are proposed to have become mobile following the acquisition of
      open reading frames (ORFs) that encode highly specific DNA endonucleases. This
      proposal implies that intron ORFs could behave as autonomously mobile entities.
      This was supported by abundant circumstantial evidence but no experiment of ORF
      transfer from an ORF-containing intron to its ORF-less counterpart has been
      described. In this paper we present such experiments, which demonstrate the
      efficient mobility of the mitochondrial nad1-i4-orf1 between two Podospora
      strains. The homing of this mobile ORF was accompanied by a bidirectional co
      conversion that did not systematically involve the whole intron sequence. Orf1
      acquisition would be the most recent step in the evolution of the nad1-i4 intron,
      which has resulted in many strains of Podospora having an intron with two ORFs
      (biorfic) and four splicing pathways. We show that two of the splicing events
      that operate in this biorfic intron, as evidenced by PCR experiments, are
      generated by a 5'-alternative splice site, which is most probably a remnant of
      the monoorfic ancestral form of the intron. We propose a sequential evolution
      model that is consistent with the four organizations of the corresponding nad1
      locus that we found among various species of the Pyrenomycete family; these
      organizations consist of no intron, an intron alone, a monoorfic intron, and a
      biorfic intron.

PMID- 9159930
TI  - Detection of convergent and parallel evolution at the amino acid sequence level.
AB  - Adaptive evolution at the molecular level can be studied by detecting convergent
      and parallel evolution at the amino acid sequence level. For a set of homologous
      protein sequences, the ancestral amino acids at all interior nodes of the
      phylogenetic tree of the proteins can be statistically inferred. The amino acid
      sites that have experienced convergent or parallel changes on independent
      evolutionary lineages can then be identified by comparing the amino acids at the
      beginning and end of each lineage. At present, the efficiency of the methods of
      ancestral sequence inference in identifying convergent and parallel changes is
      unknown. More seriously, when we identify convergent or parallel changes, it is
      unclear whether these changes are attributable to random chance. For these
      reasons, claims of convergent and parallel evolution at the amino acid sequence
      level have been disputed. We have conducted computer simulations to assess the
      efficiencies, of the parsimony and Bayesian methods of ancestral sequence
      inference in identifying convergent and parallel-change sites. Our results showed
      that the Bayesian method performs better than the parsimony method in identifying
      parallel changes, and both methods are inefficient in identifying convergent
      changes. However, the Bayesian method is recommended for estimating the number of
      convergent-change sites because it gives a conservative estimate. We have
      developed statistical tests for examining whether the observed numbers of
      convergent and parallel changes are due to random chance. As an example, we
      reanalyzed the stomach lysozyme sequences of foregut fermenters and found that
      parallel evolution is statistically significant, whereas convergent evolution is
      not well supported.

PMID- 9159931
TI  - More DNA support for a Cetacea/Hippopotamidae clade: the blood-clotting protein
      gene gamma-fibrinogen.
AB  - Recent phylogenetic analyses of DNA sequences suggest that cetaceans (whales) and
      hippopotamid artiodactyls (hippos) are extant sister taxa. Consequently, the
      shared aquatic specializations of these taxa may be synapomorphies. This
      molecular view is contradicted by paleontological data that overwhelmingly
      support a monophyletic Artiodactyla (even-toed ungulates) and a close
      relationship between Cetacea and extinct mesonychian ungulates. According to the
      fossil evidence, molecular, behavioral, and anatomical resemblances between
      hippos and whales are interpreted as convergences or primitive retentions. In
      this report, competing interpretations of whale origins are tested through
      phylogenetic analyses of the blood-clotting protein gene gamma-fibrinogen from
      cetaceans, artiodactyls, perissodactyls (odd-toed ungulates), and carnivores
      (cats, dogs, and kin). In combination with published DNA sequences, the gamma
      fibrinogen data unambiguously support a hippo/whale clade and are inconsistent
      with the paleontological perspective. If the phylogeny favored by fossil evidence
      is accepted, the convergence at the DNA level between Cetacea and Hippopotamidae
      is remarkable in its distribution across three genetic loci: gamma-fibrinogen,
      the linked milk casein genes, and mitochondrial cytochrome b.

PMID- 9159932
TI  - Positive selection and the molecular evolution of a gene of male reproduction,
      Acp26Aa of Drosophila.
AB  - The gene for a male ejaculatory protein, Acp26Aa, in four sibling species of the
      Drosophila melanogaster subgroup has previously been shown to have a
      nonsynonymous rate (Ka) of nucleotide substitution that is indistinguishable from
      the synonymous rate (Ks). By examining this gene in two other species of this
      subgroup, we found that Ka is generally large and can sometimes be more than
      twice as large as Ks. This suggests that positive selection may be operating at
      this locus of male reproduction.

PMID- 9159933
TI  - Phylogenetic relationships of artiodactyls and cetaceans as deduced from the
      comparison of cytochrome b and 12S rRNA mitochondrial sequences.
AB  - A data set of complete mitochondrial cytochrome b and 12S rDNA sequences is
      presented here for 17 representatives of Artiodactyla and Cetacea, together with
      potential outgroups (two Perissodactyla, two Carnivora, two Tethytheria, four
      Rodentia, and two Marsupialia). We include seven sequences not previously
      published from Hippopotamidae (Ancodonta) and Camelidae (Tylopoda), yielding a
      total of nearly 2.1 kb for both genes combined. Distance and parsimony analyses
      of each gene indicate that 11 clades are well supported, including the
      artiodactyl taxa Pecora, Ruminantia (with low 12S rRNA support), Tylopoda, Suina,
      and Ancodonta, as well as Cetacea, Perissodactyla, Carnivora, Tethytheria,
      Muridae, and Caviomorpha. Neither the cytochrome b nor the 12S rDNA genes resolve
      the relationships between these major clades. The combined analysis of the two
      genes suggests a monophyletic Cetacea +Artiodactyla clade (defined as
      "Cetartiodactyla"), whereas Perissodactyla, Carnivora, and Tethytheria fall
      outside this clade. Perissodactyla could represent the sister taxon of
      Cetartiodactyla, as deduced from resampling studies among outgroup lineages.
      Cetartiodactyla includes five major lineages: Ruminantia, Tylopoda, Suina,
      Ancodonta, and Cetacea, among which the phylogenetic relationships are not
      resolved. Thus, Suiformes do not appear to be monophyletic, justifying their
      split into the Suina and Ancodonta infraorders. An association between Cetacea
      and Hippopotamidae is supported by the cytochrome b gene but not by the 12S rRNA
      gene. Calculation of divergence dates suggests that the Cetartiodactyla could
      have diverged from other Ferungulata about 60 MYA.

PMID- 9159934
TI  - Phylogenetic analysis of Lymnaeid snails based on 18S rDNA sequences.
AB  - The 18S rDNA sequences of the six most common European Lymnaeidae species
      (Mollusca:Gastropoda:Basommatophora) have been obtained by direct PCR cycle
      sequencing and silver staining methods. The sequence alignment and secondary
      structures of the 18S rRNA gene of Lymnaea stagnalis, L. auricularia, L. peregra,
      L. palustris, L. glabra, and L. truncatula are analyzed. This gene proves to be a
      good marker for both specific determination and supraspecific lymnaeid phylogeny.
      The malacological importance is evident, considering the specific determination
      problems of individual snails and the present systematic chaos in Lymnaeidae due
      to their pronounced morphoanatomic uniformity, which makes a classification by
      traditional methods impossible. The majority (17) of the total of 43 nucleotide
      substituted positions appears to be confined to a small region included in helix
      E10-1 of the variable region V2, enabling species group distinction: (1) the
      first sequence is common to L. auricularia and L. peregra; (2) the second
      sequence is unique to L. truncatula; and (3) the third sequence is identical for
      L. glabra, L. palustris, and L. stagnalis. The other 26 nucleotide-substituted
      positions are dispersed over the entire gene, although four grouped nucleotide
      positions in helix 6 of V1 are of interest in distinguishing L. glabra from both
      L. palustris and L. stagnalis. The phylogenetic trees obtained by comparison with
      four other molluscan species (a polyplacophoran, two bivalves, and a
      stylommatophoran gastropod) show the presence of four well-defined subgenera
      among the genus Lymnaea sensu lato: (1) Lymnaea (Radix), (2) Lymnaea (Galba), (3)
      Lymnaea (Leptolimnaea), and (4) Lymnaea (Lymnaea). Two branches, L. auricularia
      L. peregra-L. truncatula and L. glabra-L. palustris-L. stagnalis, are worth
      mentioning from the parasitological point of view, since the two digenean species
      of large medical and veterinary impact transmitted by lymnaeids, Fasciola
      hepatica and F. gigantica, appear to be linked to the first branch.

PMID- 9159935
TI  - Evolution of the large-subunit ribosomal RNA binding site for protein L23/25.
AB  - The region of the large-subunit rRNA encompassing the D7 divergent domain is
      organized within eukaryotes in a patchwork of short conservative secondary
      structure features interspersed with more rapidly evolving sequences. It contains
      the attachment site of protein L25 (E. coli L23), which binds rRNA in the first
      stages of ribosome assembly, suggesting a crucial importance of this region in
      ribosome elaboration and functioning. A better understanding of its roles
      requires a good knowledge of its mode of structural variation during the course
      of evolution. With this aim, we sequenced the D7 region for 24 new invertebrate
      species belonging to annelids, molluscs, arthropods, and eight other deep
      branching invertebrate phyla. Their comparison allowed us to propose refinements
      in previous eukaryotic folding models. A detailed analysis of the pattern of
      variation at each position both within the D7 region and along the L23/25
      sequence by reference to previous heterologous binding experiments gives new
      insight into the rRNA-protein contacts. We identified in the D7 region and
      L23/25, respectively, six and five positions presenting a pattern of variation
      compatible with experimental results, three of which show coincident variations
      which support their possible involvement in the rRNA-L23/25 binding.

PMID- 9159936
TI  - Reanalysis of published DNA sequence amplified from cretaceous dinosaur egg
      fossil.

PMID- 9159937
TI  - Recombinant DNA sequences generated by PCR amplification.

PMID- 9159939
TI  - Two general branching patterns of xyloglucan, XXXG and XXGG.

PMID- 9159940
TI  - Abundant accumulation of the calcium-binding molecular chaperone calreticulin in
      specific floral tissues of Arabidopsis thaliana.
AB  - Calreticulin (CRT) is a calcium-binding protein in the endoplasmic reticulum (ER)
      with an established role as a molecular chaper-one. An additional function in
      signal transduction, specifically in calcium distribution, is suggested but not
      proven. We have analyzed the expression pattern of Arabidopsis thaliana CRTs for
      a comparison with these proposed roles. Three CRT genes were expressed, with
      identities of the encoded proteins ranging from 54 to 86%. Protein motifs with
      established functions found in CRTs of other species were conserved. CRT was
      found in all of the cells in low amounts, whereas three distinct floral tissues
      showed abundant expression: secreting nectaries, ovules early in development, and
      a set of subepidermal cells near the abaxial surface of the anther. Localization
      in the developing endosperm, which is characterized by high protein synthesis
      rates, can be reconciled with a specific chaperone function. Equally, nectar
      production and secretion, a developmental stage marked by abundant ER, may
      require abundant CRT to accommodate the traffic of secretory proteins through the
      ER. Localization of CRT in the anthers, which are degenerating at the time of
      maximum expression of CRT, cannot easily be reconciled with a chaperone function
      but may indicate a role for CRT in anther maturation or dehiscence.

PMID- 9159942
TI  - Independent genetic control of maize starch-branching enzymes IIa and IIb.
      Isolation and characterization of a Sbe2a cDNA.
AB  - In maize (Zea mays L.) three isoforms of starch-branching enzyme (SBEI, SBEIIa,
      and SBEIIb) are involved in the synthesis of amylopectin, the branched component
      of starch. To isolate a cDNA encoding SBEIIa, degenerate oligonucleotides based
      on domains highly conserved in Sbe2 family members were used to amplify Sbe2
      family cDNA from tissues lacking SBEIIb activity. The predicted amino acid
      sequence of Sbe2a cDNA matches the N-terminal sequence of SBEIIa protein purified
      from maize endosperm. The size of the mature protein deduced from the cDNA also
      matches that of SBEIIa. Features of the predicted protein are most similar to
      members of the SBEII family; however, it differs from maize SBEIIb in having a 49
      amino acid N-terminal extension and a region of substantial sequence divergence.
      Sbe2a mRNA levels are 10-fold higher in embryonic than in endosperm tissue, and
      are much lower than Sbe2b in both tissues. Unlike Sbe2b, Sbe2a-hybridizing mRNA
      accumulates in leaf and other vegetative tissues, consistent with the known
      distribution of SBEIIa and SBEIIb activities.

PMID- 9159944
TI  - Adenosine-5'-phosphate deaminase. A novel herbicide target.
AB  - The isolation of carbocyclic coformycin as the herbicidally active component from
      a fermentation of Saccharothrix species was described previously (B.D. Bush, G.V.
      Fitchett, D.A. Gates, D. Langley [1993] Phytochemistry 32: 737-739). Here we
      report that the primary mode of action of carbocyclic coformycin has been
      identified as inhibition of the enzyme AMP deaminase (EC 3.5.4.6) following
      phosphorylation at the 5' hydroxyl on the carbocyclic ring in vivo. When pea
      (Pisum sativum L. var Onward) seedlings are treated with carbocyclic coformycin,
      there is a very rapid and dramatic increase in ATP levels, indicating a
      perturbation in purine metabolism. Investigation of the enzymes of purine
      metabolism showed a decrease in the extractable activity of AMP deaminase that
      correlates with a strong, noncovalent association of the phosphorylated natural
      product with the protein. The 5'-phosphate analog of the carbocyclic coformycin
      was synthesized and shown to be a potent, tight binding inhibitor of AMP
      deaminase isolated from pea seedlings. Through the use of a synthetic
      radiolabeled marker, rapid conversion of carbocyclic coformycin to the 5'
      phosphate analog could be demonstrated in vivo. It is proposed that inhibition of
      AMP deaminase leads to the death of the plant through perturbation of the
      intracellular ATP pool.

PMID- 9159945
TI  - Mutations in the small subunit of ribulose-1,5-bisphosphate carboxylase/
      oxygenase increase the formation of the misfire product xylulose-1,5
      bisphosphate.
AB  - The small subunit (S) increases the catalytic efficiency of ribulose-1,5
      bisphosphate carboxylase/oxygenase (EC 4.1.1.39) by stabilizing the active sites
      generated by four large subunit (L) dimers. This stabilization appears to be due
      to an influence of S on the reaction intermediate 2,3-enediol, which is formed
      after the abstraction of a proton from the substrate ribulose-1,5-bisphosphate.
      We tested the functional significance of residues that are conserved among most
      species in the carboxy-terminal part of S and analyzed their influence on the
      kinetic parameters of Synechococcus holoenzymes. The replacements in S (F92S,
      Q99G, and P108L) resulted in catalytic activities ranging from 95 to 43% of wild
      type. The specificity factors for the three mutant enzymes were little affected
      (90-96% of wild type), but Km(CO2) values increased 0.5- to 2-fold. Mutant
      enzymes with replacements Q99G and P108L showed increased mis-protonation,
      relative to carboxylation, of the 2,3-enediol intermediate, forming 2 to 3 times
      more xylulose-1,5-bisphosphate per ribulose-1,5-bisphosphate utilized than wild
      type or F92S enzymes. The results suggest that specific alterations of the L/S
      interfaces and of the hydrophobic core of S are transmitted to the active site by
      long-range interactions. S interactions with L may restrict the flexibility of
      active-site residues in L.

PMID- 9159946
TI  - NO3- and ClO3- fluxes in the chl1-5 mutant of Arabidopsis thaliana. Does the CHL1
      5 gene encode a low-affinity NO3- transporter?
AB  - The CHL1 gene is considered to encode a low-affinity transport system (LATS) for
      NO3- in Arabidopsis thaliana (Y.-F. Tsay, J.I. Schroeder, K.A. Feldmann, N.M.
      Crawford [1993] Cell 72: 705-713). However, the anticipated reduced NO3- uptake
      by the LATS associated with loss of CHL1 gene activity in chl1-5 deletion mutants
      was evident only when plants were grown on NH4NO3. When KNO3 was the sole N
      source, NO3- accumulation and short-term tracer influx (using 13NO3- and 15NO3-)
      in leaves and roots of wild-type and mutant plants were essentially identical.
      Nevertheless, root uptake of 36CIO3- by the LATS and CIO3- accumulation in roots
      and shoots of mutant plants were significantly lower than in wild-type plants
      when grown on KNO3. One explanation for these results is that a second LATS is
      able to compensate for the chl1-5 deficiency in KNO3-grown plants. Growth on
      NH4NO3 may down-regulate the second LATS enough that the anticipated difference
      in NO3- uptake becomes apparent.

PMID- 9159947
TI  - Biochemical characterization of the aba2 and aba3 mutants in Arabidopsis
      thaliana.
AB  - Abscisic acid (ABA)-deficient mutants in a variety of species have been
      identified by screening for precocious germination and a wilty phenotype. Mutants
      at two new loci, aba2 and aba3, have recently been isolated in Arabidopsis
      thaliana (L.) Hynh. (K.M. Leon-Kloosterziel, M. Alvarez-Gil, G.J. Ruijs, S.E.
      Jacobsen, N.E. Olszewski, S.H. Schwartz, J.A.D. Zeevaart, M. Koornneef [1996]
      Plant J 10: 655-661), and the biochemical characterization of these mutants is
      presented here. Protein extracts from aba2 and aba3 plants displayed a greatly
      reduced ability to convert xanthoxin to ABA relative to the wild type. The next
      putative intermediate in ABA synthesis, ABA-aldehyde, was efficiently converted
      to ABA by extracts from aba2 but not by extracts from aba3 plants. This indicates
      that the aba2 mutant is blocked in the conversion of xanthoxin to ABA-aldehyde
      and that aba3 is impaired in the conversion of ABA-aldehyde to ABA. Extracts from
      the aba3 mutant also lacked additional activities that require a molybdenum
      cofactor (Moco). Nitrate reductase utilizes a Moco but its activity was
      unaffected in extracts from aba3 plants. Moco hydroxylases in animals require a
      desulfo moiety of the cofactor. A sulfido ligand can be added to the Moco by
      treatment with Na2S and dithionite. Treatment of aba3 extracts with Na2S restored
      ABA-aldehyde oxidase activity. Therefore, the genetic lesion in aba3 appears to
      be in the introduction of S into the Moco.

PMID- 9159948
TI  - Floral scent production in Clarkia breweri (Onagraceae). II. Localization and
      developmental modulation of the enzyme S-adenosyl-L-methionine:(iso)eugenol O
      methyltransferase and phenylpropanoid emission.
AB  - We have previously shown (R.A. Raguso, E. Pichersky [1995] Plant Syst Evol 194:
      55-67) that the strong, sweet fragrance of Clarkia breweri (Onagraceae), an
      annual plant native to California, consists of 8 to 12 volatile compounds,
      including 4 phenylpropanoids. Although some C. breweri plants emit all 4
      phenylpropanoids (eugenol, isoeugenol, methyleugenol, and isomethyleugenol),
      other C. breweri plants do not emit the latter 2 compounds. Here we report that
      petal tissue was responsible for the bulk of the phenylpropanoid emission. The
      activity of S-adenosyl-L-methionine: (iso)eugenol O-methyltransferase (IEMT), a
      novel enzyme that catalyzes the methylation of the para-4'-hydroxyl of both
      eugenol and (iso)eugenol to methyleugenol and isomethyleugenol, respectively, was
      also highest in petal tissue. IEMT activity was absent from floral tissues of
      plants not emitting (iso)methyleugenol. A C. breweri cDNA clone encoding IEMT was
      isolated, and its sequence was shown to have 70% identity to S-adenosyl-L
      methionine:caffeic acid O-methyltransferase. The protein encoded by this cDNA can
      use eugenol and isoeugenol as substrates, but not caffeic acid. Steady-state IEMT
      mRNA levels were positively correlated with levels of IEMT activity in the
      tissues, and no IEMT mRNA was observed in flowers that do not emit
      (iso)methyleugenol. Overall, the data show that the floral emission of
      (iso)methyleugenol is controlled at the site of emission, that a positive
      correlation exists between volatile emission and IEMT activity, and that control
      of the level of IEMT activity is exerted at a pretranslational step.

PMID- 9159949
TI  - Intracellular carbonic anhydrase is essential to photosynthesis in Chlamydomonas
      reinhardtii at atmospheric levels of CO2. Demonstration via genomic
      complementation of the high-CO2-requiring mutant ca-1.
AB  - Genomic complementation of the high-CO2-requiring mutant ca-1-12-1C of
      Chlamydomonas reinhardtii was achieved by transformation with DNA pools from an
      indexed cosmid library of wild-type genomic DNA. Transformation of mutant cells
      with cosmid DNA from two microtiter plates in the library produced colonies that
      grew phototrophically at atmospheric CO2 levels. Transformations with cosmid DNA
      from each of the rows and files of the two plates pinpointed one well in each
      plate with a cosmid bearing the targeted gene. Sequencing of cosmid subclones
      revealed a gene encoding a recently identified C. reinhardtii chloroplast
      carbonic anhydrase (CAH3). Transformations with chimeric constructs combining
      different portions of the wild-type and mutant genes indicated the presence of a
      mutation in the 5'-half of the gene. Comparison of mutant and wild-type gene
      sequences in this region revealed a G-to-A substitution in the mutant gene, which
      produced a nonsense codon. The data presented demonstrate that the carbonic
      anhydrase produced from the CAH3 gene is essential to the inorganic carbon
      concentrating mechanism in C. reinhardtii and that genomic complementation can be
      a facile and efficient means for isolating genes associated with defects
      affecting photosynthesis and other physiological processes in this eukaryotic
      green alga.

PMID- 9159950
TI  - Xyloglucan galactosyl- and fucosyltransferase activities from pea epicotyl
      microsomes.
AB  - Microsomal membranes from growing tissue of pea (Pisum sativum L.) epicotyls were
      incubated with the substrate UDP-[14C]galactose (Gal) with or without tamarind
      seed xyloglucan (XG) as a potential galactosyl acceptor. Added tamarind seed XG
      enhanced incorporation of [14C]Gal into high-molecular-weight products (eluted
      from columns of Sepharose CL-6B in the void volume) that were trichloroacetic
      acid-soluble but insoluble in 67% ethanol. These products were hydrolyzed by
      cellulase to fragments comparable in size to XG subunit oligosaccharides. XG
      dependent galactosyltransferase activity could be solubilized, along with XG
      fucosyltransferase, by the detergent 3-[(3-cholamidopropyl)-dimethylammonio]-1
      propanesulfonate. When this enzyme was incubated with tamarind (Tamarindus indica
      L.) seed XG or nasturtium (Tropaeolum majus L.) seed XG that had been partially
      degalactosylated with an XG-specific beta-galactosidase, the rates of Gal
      transfer increased and fucose transfer decreased compared with controls with
      native XG. The reaction products were hydrolyzed by cellulase to 14C fragments
      that were analyzed by gel-filtration and high-performance liquid chromatography
      fractionation with pulsed amperometric detection. The major components were XG
      subunits, namely one of the two possible monogalactosyl octasaccharides (-XXLG-)
      and digalactosyl nonasaccharide (-XLLG-), whether the predominant octasaccharide
      in the acceptor was XXLG (as in tamarind seed XG) or XLXG (as in nasturtium seed
      XG). It is concluded that the first xylosylglucose from the reducing end of the
      subunits was the Gal acceptor locus preferred by the solubilized pea transferase.
      These observations are incorporated into a model for the biosynthesis of cell
      wall XGs.

PMID- 9159952
TI  - Cellular basis of hypocotyl growth in Arabidopsis thaliana.
AB  - The Arabidopsis thaliana hypocotyl is widely used to study the effects of light
      and plant growth factors on cell elongation. To provide a framework for the
      molecular-genetic analysis of cell elongation in this organ, here we describe, at
      the cellular level, its morphology and growth and identify a number of
      characteristic, developmental differences between light-grown and dark-grown
      hypocotyls. First, in the light epidermal cells show a characteristic
      differentiation that is not observed in the dark. Second, elongation growth of
      this organ does not involve significant cortical or epidermal cell divisions.
      However, endoreduplication occurs, as revealed by the presence of 4C and 8C
      nuclei. In addition, 16C nuclei were found specifically in dark-grown seedlings.
      Third, in the dark epidermal cells elongate along a steep, acropetal spatial and
      temporal gradient along the hypocotyl. In contrast, in the light all epidermal
      cells elongated continuously during the entire growth period. These morphological
      and physiological differences, in combination with previously reported genetic
      data (T. Desnos, V. Orbovic, C. Bellini, J. Kronenberger, M. Caboche, J. Traas,
      H. Hofte [1996] Development 122: 683-693), illustrate that light does not simply
      inhibit hypocotyl growth in a cell-autonomous fashion, but that the observed
      growth response to light is a part of an integrated developmental change
      throughout the elongating organ.

PMID- 9159951
TI  - Cloning and overexpression of two cDNAs encoding the low-CO2-inducible
      chloroplast envelope protein LIP-36 from Chlamydomonas reinhardtii.
AB  - Chlamydomonas reinhardtii, a unicellular green alga, grows photoautotrophically
      at very low concentrations of inorganic carbon due to the presence of an
      inducible CO2-concentrating mechanism. During the induction of the CO2
      concentrating mechanism at low-CO2 growth conditions, at least five polypeptides
      that are either absent or present in low amounts in cells grown on high-CO2
      concentrations are induced. One of these induced polypeptides with a molecular
      mass of 36 kD, LIP-36, has been localized to the chloroplast envelope. The
      protein was purified and the partial internal amino acid sequences were obtained
      through lys-C digestion. Two cDNAs encoding LIP-36 have been cloned using
      degenerate primers based on the amino acid sequences. The two genes encoding LIP
      36 are highly homologous in the coding region but are completely different in the
      5'-end and 3'-end untranslated regions. The deduced protein sequences show strong
      homology to the mitochondrial carrier protein superfamily, suggesting that LIP-36
      is a chloroplast carrier protein. The regulation of the expression of these two
      genes at high- and low-CO2 growth conditions is also different. Both genes were
      highly expressed under low-CO2 growth conditions, with the steady-state level of
      LIP-36 G1 mRNA more abundant. However, neither gene was expressed at high-CO2
      growth conditions. The gene products of both clones expressed in Escherichia coli
      were recognized by an antibody raised against LIP-36, confirming that the two
      cDNAs indeed encode the C. reinhardtii chloroplast envelope carrier protein LIP
      36.

PMID- 9159953
TI  - Characterization of AtSEC12 and AtSAR1. Proteins likely involved in endoplasmic
      reticulum and Golgi transport.
AB  - Transport of cargo proteins from the endoplasmic reticulum (ER) to the cis-Golgi
      network is mediated by protein-coated vesicles. The coat, called COPII coat,
      consists of proteins that are recruited from the cytosol and interact with
      integral membrane proteins of the ER. In yeast, both cytosolic proteins
      (Sec13/31, Sec23/24, and Sar1) and ER-associated proteins (Sec12 and others) have
      been purified and characterized and it has been possible to demonstrate transport
      vesicle formation in vitro. Arabidopsis thaliana homologs of Sar1 and Sec12 have
      recently been identified, but little is known about the properties of the
      proteins or their subcellular distribution. Here we demonstrate that AtSAR1, a 22
      kD protein that binds GTP, and AtSEC12, a 43-kD GTP-exchange protein, are both
      associated with the ER. However, about one-half of the cellular AtSAR1 is present
      in the cytosol. When AtSAR1 is overexpressed in transgenic plants, the additional
      protein is also cytosolic. When tissue-culture cells are cold-shocked (12 h at 8
      degrees C), AtSAR1 levels appeared to decline and a larger proportion of the
      total protein was found in the cytosol. Given the known function of AtSAR1 in
      yeast, we propose that the amount of ER-associated AtSAR1 is an indication of the
      intensity of the secretory process. Thus, we expect that such a cold shock will
      adversely affect ER-to-Golgi transport of proteins.

PMID- 9159957
TI  - The electronic Plant Gene Register.

PMID- 9159955
TI  - A defective signal peptide tethers the floury-2 zein to the endoplasmic reticulum
      membrane.
AB  - The maize (Zea mays L.) floury-2 (fl2) mutation is associated with a general
      decrease in storage protein synthesis, altered protein body morphology, and the
      synthesis of a novel 24-kD alpha-zein storage protein. Unlike storage proteins in
      normal kernels and the majority of storage proteins in fl2 kernels, the 24-kD
      alpha-zein contains a signal peptide that would normally be removed during
      protein synthesis and processing. The expected processing site of this alpha-zein
      reveals a putative mutation alanine-->valine (Ala-->Val) that is not found at
      other junctions between signal sequences and mature proteins. To investigate the
      impact of such a mutation on signal peptide cleavage, we have assayed the 24-kD
      fl2 alpha-zein in a co-translational processing system in vitro. Translation of
      RNA from fl2 kernels or synthetic RNA encoding the fl2 alpha-zein in the presence
      of microsomes yielded a 24-kD polypeptide. A normal signal peptide sequence,
      generated by site-directed mutagenesis, restored the capacity of the RNA to
      direct synthesis of a properly processed protein in a cell-free system. Both the
      fl2 alpha-zein and the fl2 alpha-zein (Val-->Ala) were translocated into the
      lumen of the endoplasmic reticulum. The processed fl2 alpha-zein (Val-->Ala) was
      localized in the soluble portion of the microsomes, whereas the fl2 alpha-zein co
      fractionated with the microsomal membranes. By remaining anchored to protein body
      membranes during endosperm maturation, the fl2 zein may thus constrain storage
      protein packing and perturb protein body morphology.

PMID- 9159958
TI  - Cutaneous manifestations of chronic graft-versus-host disease.
AB  - Graft-versus-host disease (GVHD) occurs in a number of clinical settings. It is
      well recognized after bone marrow transplantation, an increasingly used
      therapeutic option for haematological disorders. Chronic GVHD, occurring at an
      interval greater than 100 days post-transplant, has many systemic manifestations,
      but it is the cutaneous manifestations which are most frequent and often most
      troubling to the patients. In this review article, the wide spectrum of cutaneous
      chronic GVHD (including involvement of hair, nails and mucosae), and its
      complications and associations are discussed. The clinical and histological
      features and management guidelines are presented to assist the dermatologist with
      diagnosis and treatment of this condition.

PMID- 9159959
TI  - Hypomelanosis of Ito: a syndrome requiring a multisystem approach.
AB  - Hypomelanosis of Ito can be defined as a syndrome providing a cutaneous
      epiphenomenon with a peculiar pattern of distribution, usually associated with
      disorders of the nervous system, skeleton and eyes. Four further patients are
      reported and the literature reviewed. The diagnostic criteria and the differences
      with other pigmentary diseases distributed along Blaschko's lines are
      highlighted. The main histopathological features are reported and the high
      frequency of the associated abnormalities are emphasized. The chromosomal
      findings and main genetic hypotheses are discussed. The suggested follow-up aims
      not only at the knowledge of the natural history of this condition, but also at
      its better delineation.

PMID- 9159954
TI  - Cloning and subcellular location of an Arabidopsis receptor-like protein that
      shares common features with protein-sorting receptors of eukaryotic cells.
AB  - Many receptors involved in clathrin-mediated protein transport through the
      endocytic and secretory pathways of yeast and animal cells share common features.
      They are all type I integral membrane proteins containing cysteine-rich lumenal
      domains and cytoplasmic tails with tyrosine-containing sorting signals. The
      cysteine-rich domains are thought to be involved in ligand binding, whereas the
      cytoplasmic tyrosine motifs interact with clathrin-associated adaptor proteins
      during protein sorting along these pathways. In addition, tyrosine-containing
      signals are required for the retention and recycling of some of these membrane
      proteins to the trans-Golgi network. Here we report the characterization of an
      approximately 80-kD epidermal growth factor receptor-like type I integral
      membrane protein containing all of these functional motifs from Arabidopsis
      thaliana (called AtELP for A. thaliana Epidermal growth factor receptor-Like
      Protein). Biochemical analysis indicates that AtELP is a membrane protein found
      at high levels in the roots of both monocots and dicots. Subcellular
      fractionation studies indicate that the AtELP protein is present in two membrane
      fractions corresponding to a novel, undefined compartment and a fraction enriched
      in vesicles containing clathrin and its associated adaptor proteins. AtELP may
      therefore serve as a marker for compartments involved in intracellular protein
      trafficking in the plant cell.

PMID- 9159960
TI  - An organic refrigerant for cryosurgery: fact or fiction?
AB  - Dimethylether/propane is an organic substance used as a refrigerant in a new
      cryodelivery system marketed for the treatment of warts. The objective was first
      to determine the temperatures achieved by this delivery system, both at the end
      of the applicator and in the tissues and, second, to compare with liquid nitrogen
      delivered via standard cryospray equipment (CryAC). Temperature probes were used
      to measure temperature 1 mm below the epidermis of pig trotters after freezing
      with the two delivery systems for 20 and 40 s. After freezing with
      dimethylether/propane, results showed tissue temperatures were 3 degrees C at 20
      s and 0 degree C at 40 s. Freezing with liquid nitrogen achieved -20 degrees C at
      20 s and -57 degrees C at 40 s. It was concluded that dimethylether/propane does
      not achieve tissue temperatures below 0 degree C and is not recommended in the
      use of malignant or premalignant lesions.

PMID- 9159961
TI  - Cutaneous vascular response to calcitonin gene-related peptide in psoriasis and
      normal subjects.
AB  - To determine whether cutaneous blood vessels in subjects with psoriasis possess a
      generalized inherently abnormal response to neuropeptides, the effect of three
      doses of intradermally injected calcitonin gene-related peptide (CGRP) on skin
      blood flow in normal subjects (n = 10), and on clinically normal skin (greater
      than 5 cm from psoriatic lesions) in subjects with psoriasis (n = 9) was measured
      using a laser Doppler technique. Calcitonin gene-related peptide caused a dose
      dependent increase in local blood flow in both psoriatic and normal subjects,
      which was not statistically different between the two groups. This study has
      shown that the cutaneous vasculature at sites distant from lesions of psoriasis
      (> 5 cm) is not inherently different from normal skin in its response to CGRP.

PMID- 9159963
TI  - Trigeminal trophic syndrome.
AB  - A case report of a 51-year-old woman who developed trigeminal trophic syndrome
      following craniectomy is presented. This syndrome represents trophic ulceration
      by self-induced trauma to skin in the trigeminal area. Treatment of the present
      case was complicated by the patient's underlying psychological problems.

PMID- 9159962
TI  - Allergic contact dermatitis to multiple sawdust allergens.
AB  - A 73-year-old man presented with an 8-year history of a dermatitis affecting his
      face, dorsum of hands, and forearms. He was a retired cabinet maker but still
      carried out some timber work at home. He was patch tested and found to be
      positive to colophony and saw-dust samples from four different timbers: Silky
      Oak, Queensland Hoop Pine, Radiata Pine and Australian red cedar.

PMID- 9159964
TI  - Haber's syndrome.
AB  - Haber's syndrome is a rare genodermatosis characterised by an early onset rosacea
      like eruption associated with multiple truncal keratotic lesions. The present
      study reports the clinical presentation, histology and response to therapy of two
      cases of Haber's syndrome. The cases presented with the typical features of
      Haber's syndrome. Case 1 also had diffuse palmoplantar keratoderma and prominent
      nail cuticles, and case 2 had diffuse palmar keratoderma. These features have not
      been previously reported in Haber's syndrome. In the present study Haber's
      syndrome is reviewed, and its relationship to Dowling-Degos disease and
      acropigmentation of Kitamura are discussed.

PMID- 9159965
TI  - Necrotizing cutaneous infection caused by Curvularia brachyspora in an
      immunocompetent host.
AB  - A case of necrotizing cutaneous infection in an immunocompetent host caused by
      the dematiaceous fungus, Curvularia brachyspora is presented. A 58-year-old man
      was transferred to the Prince Henry Hospital for treatment of necrotizing
      cellulitis involving both thighs that developed following cryotherapy. The
      patient did not respond to antibacterial therapy and hyperbaric oxygen. He was
      empirically commenced on intravenous amphotericin B and began to respond even
      before the pathogen C. brachyspora was identified.

PMID- 9159966
TI  - Naevus lipomatosus cutaneous superficialis.
AB  - A young male presenting with cutaneous papules and plaques in a segmental
      distribution in the pelvic girdle area is reported. The clinical features were
      suggestive of naevus lipomatosus cutaneous superficialis, but diagnostic biopsy
      is essential to demonstrate the typical histopathological features and exclude
      important differential diagnoses such as segmental neurofibromatosis.

PMID- 9159967
TI  - Nodular amyloidosis of the lip mimicking an infiltrating neoplasm.

PMID- 9159968
TI  - Pseudomonas folliculitis.
AB  - Previous reports of Pseudomonas folliculitis in children identified heated pools,
      hot tubs or spa baths as the source of the infection. This report presents a 4
      year-old female with Pseudomonas folliculitis acquired from the family bath tub.
      The source of the infection was contaminated bath toys and bath plug.

PMID- 9159969
TI  - Contact allergy to chloroacetamide.
AB  - Chloroacetamide is an uncommon skin care product allergen. A case of allergic
      contact dermatitis to this preservative is described in a patient who reacted to
      an underarm deodorant.

PMID- 9159970
TI  - Reconstruction of the upper lip with lip switch (Abbe flap reconstruction).
AB  - The lip switch operation (Abbe) is useful for full thickness defects of the upper
      lip. Careful design of the flap with pedicle take-down and inset of the flap
      after 2 weeks, leads to a predictably good reconstructive result. The flap is
      most useful for 30-50% full thickness defects of the upper lip.

PMID- 9159971
TI  - Primary cutaneous inoculation blastomycosis with some unusual features.

PMID- 9159972
TI  - Children's fears: cultural and developmental perspectives.
AB  - A modified version of the Revised Fear Survey Schedule for Children was
      administered to 865 Israeli Jewish and Israeli Bedouin children, 8-12 yr-old.
      Consistent with former studies, there was an age-related decline in fears and
      females reported more fears than males. Comparison of Jewish and Bedouin
      children's reports of fears showed significant quantitative and qualitative
      differences between the two groups. Results underscore the salience of both
      developmental and cultural factors in the development and nature of children's
      fears.

PMID- 9159973
TI  - Memory and confidence in memory judgements among individuals with obsessive
      compulsive disorder and non-clinical controls.
AB  - The present study investigated episodic memory functioning in: (1) obsessive
      compulsive disorder (OCD) patients with primarily checking symptoms (i.e.
      checkers); (2) OCD patients without checking symptoms (i.e. non-checkers); and
      (3) non-clinical control participants. On a measure of recall, all groups were
      statistically equivalent with respect to the proportion of words correctly
      recalled. Using a recognition measure, checkers were unimpaired in episodic
      memory, as compared to non-checkers and non-clinical controls. However, relative
      to the other groups, patients with checking symptoms showed decreased confidence
      in their correct and incorrect recognition memory judgements, according to their
      item-by-item self-report confidence ratings. When checkers correctly identified
      previously seen words, they were also slower to respond than were the other
      groups, supporting the view that they were less confident in their memory
      judgments relative to the other groups, which did not differ on this measure. The
      results of the present study suggest that OCD checking is not related to memory
      impairments per se but rather that checking in OCD is a symptom of decreased
      confidence in memory.

PMID- 9159974
TI  - Conditional reasoning and phobic fear: evidence for a fear-confirming reasoning
      pattern.
AB  - In two experiments we explored the role of subjects' reasoning performance in the
      persistence of phobic fear. More specifically, we investigated whether (phobic)
      subjects are prone to selectively search for danger-confirming information when
      asked to judge the validity of conditional rules in the context of general and
      phobic threats. In both experiments, participants were presented with Wason
      Selection Tasks (WST) pertaining to general and phobic threats. The WSTs
      contained safety rules (if P then no danger) and danger rules (if P then danger).
      In Experiment 1 participants were high (n = 20) and low (n = 20) spider fearful
      students, whereas in Experiment 2 participants were untreated (n = 38) and
      treated (n = 27) spider phobic women and a group of non-fearful controls (n =
      27). Both experiments showed that in the context of general threat, subjects
      predominantly rely on confirming information regarding danger rules and on
      falsifying information regarding safety rules. This reasoning strategy was not
      particularly pronounced in high fear or phobic subjects. However, only clinically
      diagnosed spider phobics displayed a similar reasoning strategy in the context of
      phobia-relevant threats. Thus, the present data seem to suggest that the mere
      perception of threat is already sufficient to activate a danger-confirming
      reasoning strategy and in case of phobic threats such a reasoning pattern
      logically serves to maintain or even enhance phobic fears.

PMID- 9159975
TI  - Embarrassment about the first panic attack predicts agoraphobia in panic disorder
      patients.
AB  - In order to find out whether contextual variables of the first panic attack and
      the person's reaction to it predict the development of agoraphobia in panic
      disorder patients, 60 patients with a DSM-III-R diagnosis of panic disorder with
      agoraphobia and 30 patients suffering from panic disorder without agoraphobia
      were interviewed about their first panic attack. Single comparisons between
      groups of agoraphobic and non-agoraphobic patients were carried out and a
      logistic regression model was applied. Occurrence of the first panic attack in
      public and the feeling of embarrassment were found to be significantly associated
      with the development of agoraphobia. It is concluded that eliciting this specific
      form of social concern at an early stage might help to identify patients at risk
      for later agoraphobia, which could, in turn, help to further specify early
      therapeutic interventions and concentrate therapeutic efforts on a high-risk
      group of panic disorder patients.

PMID- 9159976
TI  - Behavioural hearing tactics: a controlled trial of a short treatment programme.
AB  - Nineteen elderly hearing impaired subjects participated in an experimental
      treatment study and received either behavioural hearing tactics or served as
      untreated controls. Treatment was supplied in the form of a self-help treatment
      manual supplied with telephone contacts during 4 consecutive weeks. The treatment
      manual included applied relaxation, communication strategies training, advice to
      relatives, information, and coping skills. Assessments (pre-post) were conducted
      in a structured interview measuring coping behaviour. In order to evoke
      behavioural compensation small acoustic provocations were included in the
      interview. Pre-post assessments also included questionnaires, daily registered
      hearing problems, and hours of daily hearing aid use. Results showed significant
      beneficial effects in favour of the treatment in terms of self-assessed problems
      and behaviour change.

PMID- 9159977
TI  - Anxiety and memory: a recall bias for threatening words in high anxiety.
AB  - Few studies have directly examined the relationship between trait anxiety and
      explicit memory for emotionally congruent material. Evidence from clinically
      anxious subjects, however, suggests a recall bias favouring non-threatening words
      as opposed to threatening words. Two experiments are reported which examined the
      recall performance of high- and low-trait anxious subjects. Contrary to the
      clinical anxiety findings, there was evidence of a recall bias for threatening
      rather than non-threatening words in the high-trait anxious group. Further
      analysis, however, revealed that the recall bias was associated with state
      anxiety and depression levels rather than trait anxiety. The two experiments also
      showed that recall was greater for words appearing at the end of the list as
      opposed to words presented elsewhere in the list. The theoretical and
      methodological implications of these findings are discussed.

PMID- 9159978
TI  - Selective encoding of threat in panic disorder: application of a dual priming
      paradigm.
AB  - Patients with panic disorder and psychiatrically healthy control subjects
      performed a dual priming task whereby they viewed either lexical or non-lexical
      prime pairs before naming a target that had either threatening (e.g. collapse) or
      positive (e.g. cheerful) meaning. Lexical prime pairs comprised a threat word and
      a positive word, and non-lexical prime pairs comprised two rows of asterisks.
      Suggestive of a bias for encoding threat cues, panic disorder patients (under
      some conditions) were faster to name lexically primed threat targets than
      lexically primed positive targets. These data are consistent with the hypothesis
      that panic disorder is linked to an encoding bias for threatening relative
      positive information. A cognitive bias for selectively encoding threat cues may
      figure in the maintenance of anxiety states, such as panic disorder.

PMID- 9159979
TI  - Repeated exposure to interoceptive cues: does habituation of fear occur in panic
      disorder patients? A preliminary report.
AB  - In order to explore the mechanism of action of interoceptive exposure, 12 Panic
      Disorder (PD) patients were presented with two sessions of repeated CO2
      inhalation. Two distinct patterns of responding were noted. The first pattern was
      described as habituation of fear (n = 6). These patients showed decrements in pre
      and post-inhalation anxiety during both sessions (with more rapid decline during
      session 2), as well as spontaneous recovery of fear at the onset of session 2.
      The second pattern indicated fear sensitization. These patients showed relatively
      low levels of anticipatory anxiety preceding CO2 inhalation during both sessions
      but reported robust increases in fear following gas inhalation. The extent of
      this increase was slightly less during session 2 relative to session I and did
      not appear to be mediated by cardiovascular arousal, as both groups showed rapid
      HR habituation during both sessions. Results are discussed in light of current
      theories of PD and its treatment.

PMID- 9159980
TI  - Spider phobia in children: disgust and fear before and after treatment.
AB  - Fear of spiders, disgust sensitivity, and spiders' disgust-evoking status were
      assessed in a group of spider phobic girls (n = 22) who applied for treatment, in
      a group of non-phobic girls (n = 21), and in the parents of both groups of
      children. The phobic girls were tested both before and after behavioural
      treatment which consisted of 1.5 hr eye movement desensitization and reprocessing
      and 1.5 hr exposure in vivo. Findings support the idea that disgust is an
      important aspect of spider phobia: (a) spider phobic girls exhibited higher
      levels of disgust sensitivity and considered spiders per se as more disgusting
      than non-phobic girls; (b) there was a parallel decline of spider fear and
      spiders' disgust-evoking status as a result of treatment; and (c) spiders'
      disgust-evoking status was relatively strong in mothers of spider phobic girls.
      The latter finding may indicate, that the acquisition of spider fear is
      facilitated by specific parental disgust reactions when confronted with spiders.

PMID- 9159981
TI  - On the dimensionality of the Buss/Perry Aggression Questionnaire.
AB  - Buss and Perry (1992, Personality and Social Psychology, 63, 452-459) developed a
      29-item test that presumably measures four aggression-related dimensions
      (physical aggression, verbal aggression, hostility, and anger). This study
      examined the factor structure of the items with particular concern towards seeing
      how much of the structure previously noted was an artifact of differences in item
      distributions. Although the scales are intercorrelated to the point that they may
      not span four dimensions, the scales are in fact multivariate in that the
      structure is not an artifact of differences in item distributions found with
      other presumed multifactor scales.

PMID- 9159982
TI  - Assessment of worry in children and adolescents: an adaptation of the Penn State
      Worry Questionnaire.
AB  - An adaptation of the Penn State Worry Questionnaire (Meyer, Miller, Metzger &
      Borkovec, 1990, Behaviour Research and Therapy, 28, 487-495) for use with
      children and adolescents was evaluated in two studies (Penn State Worry
      Questionnaire for Children: PSWQ-C). Study I involved the examination of factor
      structure, internal consistency, and convergent and discriminant validity in a
      school sample (N = 199). The measure was found to be unifactorial and to possess
      favorable reliability and validity. Study 2 evaluated the PSWQ-C in a clinical
      sample and found significantly higher scores in children with generalized anxiety
      disorder (n = 14) than children with other anxiety disorders (n = 10) and normal
      controls (n = 10). The PSWQ-C also demonstrated good convergent and discriminant
      validity and excellent reliability in the clinical sample.

PMID- 9159983
TI  - Establishing an intracytoplasmic sperm injection (ICSI) programme for the
      treatment of male factor infertility in Ireland.
AB  - This paper chronicles the introduction and initial experiences of Intra
      Cytoplasmic Sperm Injection (ICSI) as a treatment for severe male factor
      infertility in Ireland. Following initial development of the technique using a
      bovine model, therapy was offered clinically from September 1995. Up to March
      1996 a total of 60 couples underwent the procedure. Fertilisation and embryo
      transfers were achieved in 50 of these (83.3 percent). Fourteen (23 percent)
      became clinically pregnant per cycle commenced, 28 percent per embryo transfer.
      Despite a drop in the total number of oocytes available, fertilisation rates rose
      over the 6 months of the study from 22 percent to 54 percent. There were 2
      miscarriages (14.2 percent) and the multiple pregnancy rate was 28.5 percent.
      Eight singletons, 2 twins and 2 triplet sets have been successfully delivered.
      Provided there is proper patient selection, ICSI should prove a valuable addition
      to treatment options available to infertile couples in Ireland.

PMID- 9159984
TI  - Laparoscopic cholecystectomy in adult cystic fibrosis.
AB  - Two female patients with Cystic Fibrosis, attending the Adult Regional Cystic
      Fibrosis centre at the Cork University Hospital, were investigated for upper
      abdominal pain and found to have gallstones at ultrasonography. Laparoscopic
      cholecystectomy was performed successfully and, without complication, in both
      patients.

PMID- 9159985
TI  - Skin type distribution and skin disease in Ireland.
AB  - The Irish are generally considered to have a fair complexion. We surveyed the
      distribution of skin type in an Irish city population (n = 1000). Skin type
      prevalence was as follows: type 1: 26%, type 2: 49.6%, type 3: 19.7%, type 4:
      4.3%, type 5: 0.3%, type 6: 0.1%. Sunbeds were used by 16% of the population.
      Malignant melanoma occurred in 1.4% of patients, non-melanoma skin cancer in 6%.
      The high frequency of sunbed use in a fair skinned population and the high
      incidence of skin cancer is disturbing and highlights the need for ongoing public
      health education regarding ultraviolet radiation risks.

PMID- 9159986
TI  - Are the increasing clinical demands for osmolality measurements and their
      associated electrolytes appropriate?
AB  - An audit of urine and plasma osmolalities and their associated urea and
      electrolytes over a 4 week period found that there were 124 plasma and 96 urine
      osmolality requests from 67 patients. In 21 patients (31.3 per cent), the
      osmolality results were useful in reaching a more precise diagnosis. In a further
      11 cases, urine osmolality rather than plasma would have been appropriate.
      Seventy-one per cent originated from the Intensive Therapy Unit and were largely
      requested reflexly by the hospital computer order communication system. Plasma
      osmolal gaps could be calculated on 80 occasions (65 per cent). The formula 1.89
      Na + 1.38 K + 1.03 urea + 1.08 glucose + 7.45 proved to be more accurate than the
      formula [Na+K] x 2 + urea+glucose (in mmol/L) with the latter showing a positive
      bias when compared to measured values. The osmolal gap was > 10 mOsm/Kg using the
      more complex formula on 23 occasions in 16 patients but only twice using the
      simpler calculation. These 16 patients usually had organ failure and were very
      ill. Urine sodium and potassium were measured on 72 occasions in 27 of these
      patients but urine chloride was never requested. Urine sodium < 20 mmol/L was
      found in 7 patients all of whom had relative or absolute hypovolaemia. Urine
      sodium was measured in 73 per cent of patients investigated for SIADH in general
      wards. Data was available to calculate the urine osmolal gap on 52 occasions. The
      value was > 100 mmol/L in 10 cases and this may be used as an index of the renal
      ammonium response to acidosis. Much potential derived information from simple
      indices is unused. As a result of this study, there was an approximate halving of
      the subsequent request volume.

PMID- 9159987
TI  - Prevalence of abnormal thyroid function tests in a Down's syndrome population.
AB  - As thyroid function has been documented to be of a higher prevalence in
      individuals with Down's syndrome, a study was set up to assess the thyroid status
      of these individuals. Thyroid function tests (T.F.T.s) were initially reviewed on
      100 individuals with Down's syndrome in the community and on 36 individuals who
      were residentially based. Abnormal T.F.T.s were then reviewed 3 yr later. In
      total sample of 136, initially 13 percent [n = 18] of individuals with Down's
      syndrome had abnormal T.F.T.s, 5 percent [n = 7] were established cases of
      thyroid disease and 8 percent [n = 11] were newly identified cases who had
      abnormal T.F.T.s. Three yr later 6.5 percent [n = 9] of the group who had had
      abnormal T.F.T.s continued to have abnormal T.F.T.s, 5 percent [n = 7] had
      thyroid disease and 1.5 percent [n = 2] still had biochemical evidence of thyroid
      dysfunction. There was a statistically significant increase in abnormal T.F.T.s
      in the residential sample compared to the community sample on both occasions. The
      incidence of thyroid dysfunction has been found to increase with age,
      particularly over the age of 40, however in this study the majority were under
      the age of 40 with an age range between 28.3 yr and 33.8 yr. The results in this
      study, coupled with the variability of T.F.T.s over time, highlights the need for
      regular monitoring of the thyroid status of individuals with Down's syndrome.

PMID- 9159988
TI  - Cryptogenic organising pneumonitis in association with acute viral hepatitis.
AB  - Case history of a 54 yr old lady with acute viral hepatitis who developed
      cryptogenic organising pneumonitis. The patient was receiving corticosteroids at
      the time of onset of symptoms.

PMID- 9159989
TI  - Decline in the incidence of late diagnosed congenital dislocation of the hip.
AB  - INTRODUCTION: We reviewed the incidence of early and late diagnosed CDH over a 13
      yr period in a single maternity with a well established follow-up program and a
      stable population base. In March 1991, all newborn infants were nursed in the
      lateral or supine position, having previously been nursed prone. In addition, a
      dedicated hip screener was appointed in October 1992. We wished to determine
      whether these changes could have led to a reduction in late diagnosed CDH.
      METHODS: Babies with suspected CDH were seen by a single consultant orthopaedic
      surgeon within 1 week of birth. Splints were not applied until diagnosis was
      confirmed by the orthopaedic surgeon. The study period was from January 1983 to
      December 1995, inclusive. RESULTS: 37,383 babies were born during the study
      period, an average of 2,876 births per annum. The average rate of babies referred
      to the orthopaedic surgeon was 12.8 per 1,000 (range 5.5-28.2 per 1,000). The
      average incidence of babies splinted early was 7.19 per 1,000 (range 4.0-14.1 per
      1,000) with no discernible increase or decrease over the yrs. In contrast, there
      was a clear reduction in the incidence of late diagnosed CDH; 42/24,713 births
      (January 1983-February 1992) compared to only 2/12,673 births (March 1992
      December 1995; p < 0.0001. Twelve of the 44 infants (27 per cent) diagnosed with
      late diagnosed CDH were discovered by the policy of routine hip radiographs at 6
      months of age of all babies born by breech presentation (2/12) or those with a
      positive family history of CDH in a first degree relative (10/12). Six others had
      a diagnosis of CDH confirmed by X-rays done at 6 months of age because of doubts
      about their examination in the newborn period. CONCLUSIONS: Nursing infants in
      the supine or lateral position and the introduction of a single hip screener were
      associated with a reduction in the incidence of late diagnosed CDH. Routine hip
      radiographs of high risk infants at 6 months of age proved to be a valuable
      safety net in detecting a significant proportion of previously undetected infants
      with CDH.

PMID- 9159990
TI  - Is repeat laparotomy of value in patients with suspected intra-abdominal sepsis
      in the intensive care unit?
AB  - The management of patients with suspected post laparotomy intra-abdominal sepsis
      poses a major therapeutic challenge to clinicians. The mortality is high and the
      optimal interventional modality remains ill-defined. We define the incidence,
      diagnostic methodology, pre- and postoperative findings and outcome of patients
      going from the intensive care unit for a repeat laparotomy in search of abdominal
      sepsis over a one year period. Fifteen patients were included with an overall
      mortality of 60 percent. In 6 cases more than one relaparotomy was performed with
      a mortality of 50 percent. Sepsis was found in 14 of the 15 cases with a
      mortality of 57 percent and the patient with a normal relaparotomy died. The
      primary surgery was elective in 26 percent of cases and the mortality was 50
      percent. All the non-survivors required mechanical ventilation, inotropic support
      and continuous veno-veno haemodialysis while the survivors required less organ
      support. Radiological assessment (ultrasound scan and CT scan) were no better at
      predicting an abnormal relaparotomy than clinical assessment. Higher mortality
      rates were associated with increasing age and multi-system organ failure (p <
      0.05).

PMID- 9159991
TI  - Guidelines for the use of phototherapy and photochemotherapy in Ireland.

PMID- 9159993
TI  - Medicine and the Dublin Philosophical Society (1683-1686).

PMID- 9159992
TI  - Puncture wound related pseudomonas infections of the foot in children.
AB  - Eleven children with Pseudomonas aeruginosa infection complicating foot puncture
      wounds were reviewed. Delay in presentation (mean 2 days) and diagnosis (mean 9
      days) due to a paucity of clinical signs of deep infection was characteristic of
      this condition. Septic arthritis (5 patients) and osteomyelitis (3 patients) were
      frequent complications. Treatment involved multiple surgical debridements and
      prolonged intravenous antibiotic therapy. The clinical outcome was good although
      long-term radiographic changes were common.

PMID- 9159994
TI  - Bullous pemphigoid and rheumatoid arthritis: is there disease association?

PMID- 9159995
TI  - Musculo-cutaneous nerve nomenclature: in the arm or the leg?

PMID- 9159996
TI  - More IMG involvement needed.

PMID- 9159997
TI  - Osteoporosis 2000.

PMID- 9159998
TI  - Identification of patients at risk of osteoporosis.

PMID- 9159999
TI  - Epidemiologic and economic considerations of osteoporosis.

PMID- 9160001
TI  - Bone mineral density testing by DEXA.

PMID- 9160000
TI  - AACE Clinical Practice Guidelines for the Prevention and Treatment of
      Postmenopausal Osteoporosis.

PMID- 9160002
TI  - Osteoporosis legislation 1996. Chapter 96-282. House bill no. 397.

PMID- 9160004
TI  - We are all digital.

PMID- 9160003
TI  - Deaf services. The ADA and risk management.

PMID- 9160005
TI  - Florida physicians' guide to on-line information and the Internet.
AB  - The combination of new computing technology with progress in data communications
      over wide geographic areas offers computer users the opportunity to publish
      information to each other rapidly across wide geographic expanses. The concept of
      networking computers to gain access to the most recent and widest range of
      available information is consistent with the aims and methods of quality health
      care. The Internet is the ultimate extension to the computer network concept- an
      unlimited link of digital servers and users world-wide, united by common
      protocols for purposes of information exchange, self-policed and without central
      controls. Although the concept is attractive, on-line servers and the Internet
      are sophisticated information tools whose most effective use requires that users
      be oriented to basic concepts and conventions. This article summarizes the basic
      conventions in computer networking and data security; the differences in concept
      and use between bulletin board systems (BBSes), online systems, and the Internet
      for information access; the various classes of Internet information resources and
      their uses; the basic use of search engines to expedite information retrieval in
      the Internet; and offers practical advice in choosing methods of Internet access.

PMID- 9160006
TI  - Medicine and the Internet. What can I learn from the Internet?
AB  - What is the Internet? The Internet is the biggest network of information
      resources the world has ever seen and is growing rapidly each day. The Internet
      and the World Wide Web (The Web) represent the first technology to fully
      integrate the communications found on bookshelves, magazine racks, catalog files,
      fax machines, symposiums, in television/radio studios and the common mail system
      into a global infrastructure with extraordinary capabilities to deliver timely
      health care information. Unlike conventional media like newspapers or television,
      the Internet provides rapid one-to-one communication between millions of
      individuals. Television and newspapers communicate from "a few" (the writers and
      advertisers) to "many" (the readership). On the Internet, everyone is a "peer,"
      being both an information provider and consumer on a 24-hour, 7-day a week basis.
      This article will discuss ways you can use the Internet's information resources
      in your own personal and professional life.

PMID- 9160007
TI  - Ten basic World-Wide Web sites for Florida physicians.
AB  - The Internet is a rapidly growing information resource for rapid publication and
      access to information. While it has attracted a certain mystique and is
      undoubtedly attractive as an information source, its rapid and chaotic growth
      mitigates against ease of use for novices. The authors-all associated with health
      care providers in the Dade/Broward market-offer the novice user their best
      assessment for initial Web sites to explore for health care information, and
      general guidance on using Internet search engines to direct effective searches.

PMID- 9160008
TI  - Telemedicine in the '90s.
AB  - BACKGROUND: Telemedicine emerged in the 1950's and declined during the 1970s and
      1980s. Its reemergence in the 1990s generally tracks communications technological
      advances. Though its major applications have traditionally been confined to rural
      and under-served areas, telemedicine's application grows on a nearly daily basis.
      Broadly defined, telemedicine describes the transfer of medical data over
      facsimile or telephone and video conferencing. Though traditionally applied to
      patient care, it is increasingly being employed in the area of physician
      education. The Florida Medical Association's computer CME developments are one
      example.

PMID- 9160009
TI  - The Internet & Healthcare Education: HELIX.
AB  - With the advent of the World Wide Web (WWW), we are now on the cusp of a
      revolution in computer technology that will dramatically enhance medical
      education. An historical analogy might be Johann Gutenberg's invention of movable
      type in the 1400's-radically decreasing the cost, time, and expertise required to
      reproduce printed materials. Now, the WWW can decrease the cost of disseminating
      medical educational materials. When an educational module is authored for the
      Web, it can be placed on a computer "server" which in turn, distributes the
      program on the WWW to anyone with a computer and Internet access. Rapidly
      emerging standards are being developed to allow increasingly rich educational
      experiences on the Internet. With the introduction of HTML (hypertext markup
      language), a standardized method of placing text and graphics, as well as the
      connections between them, was created.

PMID- 9160010
TI  - The preservation of good medicine is dependent on information.
AB  - BASIS FOR THE ARGUMENT. Virtually all physicians feel a growing loss of control
      in their private practices and a sense of disillusionment with today's medicine.
      In the good ole days of modern medicine, medicine was a profession and a
      physician had a special bond with his patient and his community. In a
      constructive sense, a physician had power which was used to practice good
      medicine and provided part of the basis for a satisfying practice. As modern
      medicine evolved, the complexity of the science and the cost of technology forced
      new, non-physician players into the process of providing patient care. Over time,
      costs seemed to become the predominant theme and medicine became a business. One
      fact is certain, that as a result of this process, physicians lost power. Less
      provable, but widely believed, is that patient care suffered. There is also a
      growing concern that clinical outcomes are less than optimal and that health care
      services are more costly than they need to be because of wide variations in the
      diagnostic and treatment processes.

PMID- 9160011
TI  - Physical activity and cardiovascular health.
AB  - OBJECTIVE: To provide physicians and the general public with a responsible
      assessment of the relationship between physical activity and cardiovascular
      health. PARTICIPANTS: A non-Federal, nonadvocate, 13-member panel representing
      the fields of cardiology, psychology, exercise physiology, nutrition, pediatrics,
      public health, and epidemiology. In addition, 27 experts in cardiology,
      psychology, epidemiology, exercise physiology, geriatrics, nutrition, pediatrics,
      public health, and sports medicine presented data to the panel and a conference
      audience of 600. EVIDENCE: The literature was searched through Medline and an
      extensive bibliography of references was provided to the panel and the conference
      audience. Experts prepared abstracts with relevant citations from the literature.
      Scientific evidence was given precedence over clinical anecdotal experience.
      CONSENSUS PROCESS: The panel, answering predefined questions, developed their
      conclusions based on the scientific evidence presented in open forum and the
      scientific literature. The panel composed a draft statement that was read in its
      entirety and circulated to the experts and the audience for comment. Thereafter,
      the panel resolved conflicting recommendations and released a revised statement
      at the end of the conference. The panel finalized the revisions within a few
      weeks after the conference. CONCLUSIONS: All Americans should engage in regular
      physical activity at a level appropriate to their capacity, needs, and interest.
      Children and adults alike should set a goal of accumulating at least 30 minutes
      of moderate-intensity physical activity on most, and preferably, all days of the
      week. Most Americans have little or no physical activity in their daily lives,
      and accumulating evidence indicates that physical inactivity is a major risk
      factor for cardiovascular disease. However, moderate levels of physical activity
      confer significant health benefits. Even those who currently meet these daily
      standards may derive additional health and fitness benefits by becoming more
      physically active or including more vigorous activity. For those with known
      cardiovascular disease, cardiac rehabilitation programs that combine physical
      activity with reduction in other risk factors should be more widely used.

PMID- 9160012
TI  - Transpupillary thermotherapy in choroidal melanoma.

PMID- 9160013
TI  - Smith-Magenis syndrome.

PMID- 9160014
TI  - Occludable angles in a Vietnamese population.

PMID- 9160015
TI  - Complications of small clear-zone RK.

PMID- 9160016
TI  - Healthcare economics and endophthalmitis.

PMID- 9160017
TI  - An investigation of the hospital charges related to the treatment of
      endophthalmitis in the Endophthalmitis Vitrectomy Study.
AB  - PURPOSE: The purpose of the study is to assess the hospital charges associated
      with the treatment of endophthalmitis using a sample of patients from the
      Endophthalmitis Vitrectomy Study (EVS). METHODS: The Endophthalmitis Vitrectomy
      Study was a multicenter, randomized clinical trial with a two-by-two factorial
      design to compare immediate pars plana vitrectomy to tap-biopsy and to compare
      the use of systemic antibiotics (intravenous) to no intravenous antibiotics in
      the management of postoperative endophthalmitis. Hospital charge data were
      collected retrospectively from 129 patients from the 4 clinical centers
      participating in this ancillary study. This represents 31% of the total
      Endophthalmitis Vitrectomy Study population. An analysis of variance was used to
      compare hospital charges across center and treatment. A charge-effectiveness
      analysis compared measures the effectiveness across treatment groups. The annual
      savings of hospital charges in the United States was estimated for a range of
      annual incidence rates of endophthalmitis. RESULTS: The use of intravenous
      antibiotics significantly increased hospital charges. Patients undergoing
      vitrectomy had significantly higher hospital charges than did patients undergoing
      tap-biopsy. The most charge-effective treatment for patients presenting with
      light perception only vision was immediate vitrectomy, whereas the most charge
      effective treatment for patients presenting with better vision was tap-biopsy.
      Factors other than treatment independently associated with hospital charges were
      female sex, history of diabetes, symptom of red eye, and baseline vision of light
      perception only. CONCLUSIONS: Assuming the results of the Endophthalmitis
      Vitrectomy Study were used as a guide for the treatment of endophthalmitis, the
      estimated annual nationwide reduction of hospital charges would be between $7.6
      million and $40.0 million.

PMID- 9160018
TI  - Delayed-onset endophthalmitis associated with conjunctival filtering blebs.
AB  - OBJECTIVE: The purpose of the study is to evaluate the causative organisms,
      treatment methods, and visual acuity outcomes of patients treated for delayed
      onset endophthalmitis associated with conjunctival filtering blebs. METHODS: The
      medical records of 32 patients with conjunctival filtering bleb-associated
      endophthalmitis treated at the Bascom Palmer Eye Institute between 1989 and 1995
      were reviewed retrospectively. Bleb-associated endophthalmitis was diagnosed at 1
      month or more after surgery in all patients. Patients with bleb infections only
      but without, signs of intraocular infection were excluded from this series.
      RESULTS: Previous antimetabolite therapy was used in 20 patients, including
      mitomycin C in 14 and 5-fluorouracil in 6. Streptococcal species were the most
      frequently cultured organisms occurring in 15 (47%) of 32 eyes. Of the 32
      patients, 30 received intraocular antibiotics. The initial treatment included a
      pars plana vitrectomy in 18 patients and a vitreous tap without vitrectomy in 12
      patients. Two of three patients who presented with no light perception vision
      were treated by evisceration. Overall, 15 (47%) of 32 patients achieved a final
      visual acuity of 20/400 or better. Of those patients with Streptococcal species
      cultured from the eye, 6 (40%) of 15 had a visual acuity of 20/400 or better
      compared to 9 (52%) of 17 in patients with non-Streptococcal species.
      CONCLUSIONS: Delayed-onset endophthalmitis associated with conjunctival filtering
      blebs is a current and future concern, especially with increasing use of
      mitomycin C. The Streptococcal species are a common causative organism. Despite
      current treatment of these patients, the visual acuity outcomes generally are
      worse than in patients with acute-onset endophthalmitis after cataract surgery.

PMID- 9160019
TI  - Evidence for breaches of the retinal vasculature in acquired immune deficiency
      syndrome angiopathy. A fluorescent microsphere study.
AB  - PURPOSE: The author studied the retinal vasculature in patients with acquired
      immune deficiency syndrome (AIDS) by infusion of microspheres impregnated with
      fluorescent dye. METHODS: Experimental study of the structural integrity of the
      retinal microvasculature in 14 autopsy patients with AIDS was compared with age-
      and gender-matched control retinas. MATERIALS: Fourteen autopsy eyes from
      patients with AIDS, eight autopsy eyes from immunosuppressed control patients,
      and four autopsy eyes from nonimmunosuppressed control patients were studied.
      EXPERIMENTAL METHOD: The central retinal arteries of autopsy eyes were perfused
      with fluorescent microspheres of 10 and 200 nm in diameter. The retinas were
      dissected from the eyes and viewed by fluorescence microscopy. RESULTS: Vascular
      breaches permeable to 200-nm microspheres were discovered in eyes from patients
      with AIDS. Ruptured microaneurysms were identified at the center of retinal
      hemorrhages in 7 of 14 eyes from patients with AIDS and 5 of 8 immunosuppressed
      control eyes. Leakage around microaneurysms occurred even in the absence of
      hemorrhage and were more frequent in eyes from patients with AIDS (11/14) than in
      control eyes (3/12). Cotton wool patches were surrounded by tortuous retinal
      vessels and microaneurysms. CONCLUSIONS: Ruptured microaneurysms are a frequent
      cause of retinal hemorrhage in immunosuppressed patients. Breaches in
      microaneurysms occur even in the absence of hemorrhage. These breaches are often
      at least 200 nm in diameter, a size that is permissive to capsids and virions of
      cytomegalovirus (CMV). Ruptured and/or leaky microaneurysms are potential sources
      of CMV permeation of the blood-retinal barrier. Breaches of the retinal
      microvasculature are not specific to patients with AIDS and occur frequently in
      other immunosuppressed patients.

PMID- 9160020
TI  - Indocyanine green hyperfluorescence associated with serous retinal pigment
      epithelial detachment in age-related macular degeneration.
AB  - PURPOSE: Indocyanine green (ICG) angiography may improve visualization of
      choroidal neovascularization (CNV) associated with serous retinal pigment
      epithelial detachment (RPED) in age-related macular degeneration (AMD). The
      features of ICG hyperfluorescence associated with serous RPED and therapeutic
      effect of ICG-directed laser photocoagulation in eyes with serous RPED is
      evaluated. DESIGN: Retrospective review of all simultaneous fluorescein/ICG
      angiograms (n = 918) performed over an 18-month period to identify 44 eyes in 39
      patients with serous RPED secondary to AMD on fluorescein angiography.
      PARTICIPANTS: Thirty-nine patients with AMD, aged 53 to 89 years, participated.
      INTERVENTION: Eyes were nonrandomly treated with ICG-directed laser
      photocoagulation or observation. MAIN OUTCOME MEASURES: Characteristics of ICG
      hyperfluorescence associated with a serous RPED are reviewed. Final visual acuity
      and anatomic appearance of the serous RPED are given. RESULTS: Twenty-three (52%)
      of the 44 eyes had an isolated serous RPED without obvious CNV, and 21 (48%) of
      the 44 eyes had a serous RPED associated with occult CNV on fluorescein
      angiography. Indocyanine green angiography demonstrated underlying CNV in 19 eyes
      (83%) with an isolated serous RPED and in all 21 eyes (100%) with serous RPED and
      occult CNV. The pattern of ICG hyperfluorescence revealed focal CNV in 15 eyes
      and plaque CNV in 4 eyes with an isolated serous RPED. In eyes with serous RPED
      and occult CNV, focal CNV and plaque CNV were noted with ICG in 8 and 13 eyes,
      respectively. No follow-up was available for two eyes. Twenty eyes were treated
      with ICG-directed laser photocoagulation. In these eyes, the visual acuity
      remained stable in 6 eyes (30%) and decreased in 14 eyes (70%). Twenty-two eyes
      were observed, and the visual acuity remained stable in 8 (36%), improved in 2
      (9%), and decreased in 12 eyes (55%). CONCLUSIONS: Although ICG angiography may
      enhance visualization of CNV associated with serous RPED in AMD, ICG-directed
      laser treatment did not appear to improve visual acuity when compared with
      observed eyes in this series.

PMID- 9160021
TI  - Sun exposure and age-related macular degeneration. An Australian case-control
      study.
AB  - BACKGROUND: The notion that sun exposure is a risk factor for age-related macular
      degeneration (AMD) is widespread, but studies have not shown this conclusively.
      METHODS: To test the hypothesis that AMD cases have greater ocular sun exposure
      than control subjects, the authors compared 409 cases with 286 control subjects
      resident in Newcastle, Australia. Sensitivity to sun and glare of the
      participants was characterized. Sun exposure was estimated from detailed
      histories and was validated against sun-seeking or avoidance behavior expected,
      given sun sensitivity and history of treatment for skin neoplasia. RESULTS:
      Contrary to the authors' hypothesis, control subjects had greater median annual
      ocular sun exposure (865 hours) than cases (723 hours), Mann-Whitney U (U) =
      45704, z = -4.9, P > 0.0001. Cases had poorer tanning than did control subjects
      (mean 2 = 18.2, 4 df, P = 0.001) and as young adults were more sensitive to
      glare, odds ratio (OR), 2.5; 95% confidence intervals (CIs), 1.8 to 3.5. After
      stratifying by tanning ability, in the poor-tanning group, the median annual sun
      exposure of control subjects (685 hours) exceeded that of cases (619 hours), U =
      6556, z = -1.9, P = 0.06. Among people who tanned well, control subjects also had
      significantly greater annual sun exposure than did cases (940 vs. 770 hours), U =
      16263, z = -3.7, P = 0.0002. CONCLUSIONS: Sensitivity to glare and poor tanning
      ability are markers of increased AMD risk. Sun sensitivity confounds study of the
      postulated AMD-sunlight link. Despite analyses stratified by sun sensitivity, sun
      exposure was greater in control subjects than in cases with AMD.

PMID- 9160022
TI  - Uveal melanoma. Comparison of the prognostic value of fibrovascular loops, mean
      of the ten largest nucleoli, cell type, and tumor size.
AB  - PURPOSE: This study was performed to determine the prognostic significance of the
      presence of loops defined as periodic acid-Schiff-positive fibrovascular septa
      that completely surround lobules of tumor cells in cases of uveal melanoma.
      METHODS: The presence of loops was evaluated using an ordinary light microscope
      and routinely stained periodic acid-Schiff and hematoxylin sections from 496
      posterior uveal melanomas without knowledge of the follow-up data on the patient.
      RESULTS: At 15 years, survival decreased from 67.5% to 33.8% when complete loops
      were present. Univariate Cox regression analysis indicated that the presence of
      loops was an indicator of poor outcome, and was better than age but not as good
      as the mean diameter of the largest nucleoli, cell type, or tumor size.
      CONCLUSIONS: The presence of loops, as evaluated in this study, was not as strong
      an indicator of poor outcome as were loops assessed in a previous study of 234
      cases from another laboratory. The authors suspect this difference may be due to
      their only using routinely stained sections without a green filter, as was used
      in previously reported studies. The authors description of loops does not require
      any special equipment and gives sufficiently useful results to justify its
      inclusion by the pathologist in reports of such specimens. A description of
      vascular loops should be added to the use of the modified Callender cell type,
      tumor dimensions, mitotic count, extraocular extension, and lymphocytic
      infiltration in the final pathologic report.

PMID- 9160023
TI  - Intraocular pressure elevation after simple pars plana vitrectomy.
AB  - PURPOSE: The purpose of the study is to determine the incidence, timing, and
      severity of variability in the intraocular pressures (IOPs) from baseline after
      simple pars plana vitrectomy. METHODS: A prospective study was performed in 25
      consecutive patients undergoing simple pars plana vitrectomy. Intraocular
      pressures were measured before surgery, immediately after surgery, and then at 2,
      4, 6, 12, and 24 hours after surgery. RESULTS: The mean IOP was elevated
      significantly 2 hours after surgery when compared with the mean immediate
      postoperative IOP (30.3 mmHg +/- 11.0 mmHg vs. 17.4 mmHg +/- 7.0 mmHg, P <
      0.001). A steady decline was seen at all succeeding timepoints. The 24-hour mean
      (17.3 mmHg +/- 4.3 mmHg, P = 0.923) was similar to baseline. Ninety-two percent
      of eyes had a 2-hour postoperative IOP that was higher than the IOP at the
      completion of surgery. Forty percent of patients required medical management for
      IOP greater than or equal to 30 mmHg. CONCLUSIONS: Significant IOP elevation can
      occur after simple pars plana vitrectomy. The optimal time for detecting the
      pressure rise during the first 24 hours is 2 hours after surgery.

PMID- 9160024
TI  - Removal of retained lens fragments after phacoemulsification reverses secondary
      glaucoma and restores visual acuity.
AB  - PURPOSE: The purpose of the study is to evaluate the effect of vitrectomy on
      secondary glaucoma and visual acuity outcomes in patients with retained lens
      fragments after phacoemulsification. METHODS: A retrospective analysis of 126
      patients who had vitrectomy for retained lens fragments after phacoemulsification
      during the 3-year period between January 1, 1993, and December 31, 1995. RESULTS:
      Glaucoma, defined as an intraocular pressure of greater than or equal to 30 mmHg,
      occurred in 42 (36.8%) of 114 patients before vitrectomy and in 4 patients (3.2%)
      of 126 after vitrectomy. There were no differences in the rates of persistent
      glaucoma regardless of the intervals between cataract surgery and the vitrectomy:
      less than or equal to 1 week, 2 patients (4.1%); greater than 1 week to less than
      or equal to 4 weeks, 1 patient (2.5%) and greater than 4 weeks, 1 patient (2.6%).
      The visual acuity was 20/40 or better in 13 patients (11.4%) before vitrectomy
      and in 75 patients (59.5%) after vitrectomy. The rates of visual acuity 20/40 or
      better also were similar for all intervals: less than or equal to 1 week, 29
      patients (59.2%); greater than 1 week to less than or equal to 4 weeks, 22
      patients (56.4%) and greater than 4 weeks, 24 patients (63.1%). CONCLUSIONS:
      Vitrectomy for removal of retained lens fragments reduces secondary glaucoma and
      yields favorable visual acuity outcomes. In eyes with elevated intraocular
      pressure, early vitrectomy generally is recommended, but delayed vitrectomy also
      has favorable outcomes.

PMID- 9160025
TI  - Decentration and tilt of polymethyl methacrylate, silicone, and acrylic soft
      intraocular lenses.
AB  - PURPOSE: The purpose of the study is to investigate the periodic changes
      regarding the decentration and tilt of the intraocular lens (IOL) and to compare
      any differences in the decentration and tilt among polymethyl methacrylate
      (PMMA), silicone, and acrylic soft IOLs. METHODS: A total of 225 cataractous eyes
      undergoing IOL implant surgery were randomized into 3 groups based on the type of
      IOL: group A, one-piece PMMA IOL; group B, three-piece silicone IOL; and group C,
      three-piece acrylic soft IOL. Both the length of the decentration and the degree
      of the tilt of the IOL were quantitated using the Anterior Eye Segment Analysis
      System (EAS-1000). All eyes underwent EAS-1000 examinations at 1 week as well as
      1, 3, 6, 9, and 12 months after surgery. RESULTS: All IOLs were confirmed to be
      implanted accurately in the capsular bag after continuous curvilinear
      capsulorhexis was accomplished. No statistically significant differences were
      observed regarding the IOL decentration or tilt between the various postoperative
      periods in any of the three IOL groups. Furthermore, the differences regarding
      both the IOL decentration and the tilt between the three IOLs were not determined
      to be statistically significant throughout the observation period. CONCLUSIONS:
      As long as the IOL was placed properly in the capsular bag after the continuous
      capsulorhexis, neither the decentration nor the tilt of the IOL showed a
      significant progression up to 12 months after surgery. Furthermore, both the
      extent of the decentration and tilt almost were the same among the PMMA,
      silicone, and acrylic soft IOLs.

PMID- 9160026
TI  - International applicability of the VF-14. An index of visual function in patients
      with cataracts.
AB  - PURPOSE: There is increased recognition that a rigorous approach to functional
      assessment should complement the assessment of clinical status. The authors
      compare the reliability, validity, and responsiveness to clinical change of a
      visual function index (VF-14) in non-U.S. and in U.S. patients with cataracts.
      DESIGN: An observational longitudinal study was performed. PARTICIPANTS: One
      thousand four hundred seven first eye cataract surgery patients were recruited in
      four international sites: Manitoba (Canada), Denmark, Barcelona (Spain), and the
      United States. INTERVENTION: Patients were evaluated before cataract surgery and
      at a 4-month postoperative follow-up visit. Patients completed the preoperative
      interview and the clinical examination (766 in the United States, 152 in
      Manitoba, 291 in Denmark, and 198 in Barcelona), and 91.3% of those (1284) also
      completed the 4-month postoperative follow-up interview and were evaluated
      postoperatively by an ophthalmologist. MAIN OUTCOME MEASURES: The authors used
      the following measures: the visual function index (VF-14), the Sickness Impact
      Profile (SIP), global measures of patients' trouble and satisfaction with vision,
      and best-corrected visual acuity (VA) in each eye. RESULTS: The VF-14 showed a
      high internal consistency reliability level in all sites (Cronbach's alpha
      coefficients > or = 0.84). Correlation of preoperative visual function index
      scores with the Vision-Related SIP was strong (r = -0.68 in non-U.S. and r = 
      0.57 in U.S. patients) and with VA in the eye with better vision was moderate (r
      = 0.40 and r = 0.27, respectively), the pattern of relationships being very
      similar among U.S. and non-U.S. patients. In patients with only first-eye surgery
      who reported that their initial trouble with vision had improved, the amount of
      change in visual function as assessed by the VF-14 (effect size) was large (1.01
      for the non-U.S. patients and 1.17 for the U.S. patients). CONCLUSIONS: The non
      U.S. versions of the visual function index (VF-14) analyzed are as reliable,
      valid, and responsive to clinical change as the original U.S. version. These
      versions are appropriate for international studies of cataract patients outcomes
      and possibly in routine clinical practice.

PMID- 9160027
TI  - Pointwise univariate linear regression of perimetric sensitivity against follow
      up time in glaucoma.
AB  - PURPOSE: The authors compared pointwise univariate linear regression (ULR) of
      sensitivity against follow-up as an indicator of visual field progression with
      that of the corresponding ULR of mean deviation (MD) and with the Glaucoma Change
      Probability (GCP) analysis. The authors determined the influence of the number
      and sequence of prior examinations on the slope of the pointwise function.
      METHODS: Univariate linear regression was undertaken at each stimulus location on
      the arbitrarily assigned left eyes of 38 patients with glaucoma examined with the
      Humphrey Field Analyzer Programs 30-2 or 24-2 (stimulus size III, Humphrey
      Instruments Inc, San Leandro, CA). The mean age was 59.0 years (standard
      deviation [SD] = 12.9), the mean number of fields per patients was 12.0 (SD =
      2.8), and the mean duration of follow-up was 6.0 years (SD = 1.6). RESULTS: Four
      patients showed statistically significant MD slopes. Of the 34 patients
      exhibiting a nonsignificant MD slope, 15 exhibited clusters of at least two
      contiguous progressing locations. Less than half of these locations were
      designated as progressing by GCP. The GCP detected less than one third of the
      locations considered progressing by ULR for the last six fields in the series:
      this was attributed to the nonlinear nature of the decline in sensitivity.
      CONCLUSIONS: The degree of agreement between the outcomes of ULR and GCP was
      dependent on the quality of the collected data, the magnitude of the baseline
      sensitivity, the extent and type of the subsequent visual field progression, and
      the position of the fields within the examination series. Good agreement was
      illustrated at those locations where the deterioration fell outside the limits of
      expected variability in stable glaucoma.

PMID- 9160028
TI  - Ulcerative keratitis in bullous keratopathy.
AB  - PURPOSE: The authors review a large series of patients with bullous keratopathy
      (BK) to analyze the frequency of ulcerative keratitis, and determine the
      contributory roles of bullae, bandage soft contact lenses, steroids, and
      prophylactic antibiotics. METHODS: A retrospective review of all cases of
      pseudophakic or aphakic bullous keratopathy presenting to the cornea service
      between January 1, 1986 and September 1, 1995 was performed. The influence of
      time, bullae, bandage contact lenses, steroids, and prophylactic antibiotics was
      evaluated by actuarial methods and multivariate analysis. RESULTS: Nine hundred
      eighteen patients were included in this study, 44 (4.7%) of whom had infectious
      or inflammatory complications; 813 cases were available for statistical analysis.
      Steroids (P < 0.0001), bandage soft contact lens use (P = 0.004), and bullae (P =
      0.01) had statistically significant independent effect on the risk of developing
      ulcerative keratitis, and the combination of steroids and bandage lenses yielded
      the highest risk (P < 0.001). Propylactic antibiotic use paradoxically had a
      statistically significant association with ulcerative keratitis in these patients
      (P = 0.01). Increasing BK time was also associated with ulcer development, and
      the risk remained relatively constant over the 60 months of the study.
      Streptococcus was the most frequent organism cultured. CONCLUSIONS: Ulcerative
      keratitis developed in 4.7% of patients with bullous keratopathy. Prolonged BK
      time alone was a risk factor for infection. The strongest single additional risk
      factor for ulcer development was steroid use, followed by bandage soft contact
      lens use, and their simultaneous use had the greatest effect. The presence of
      bullae was also a risk factor for infection, and prophylactic antibiotic use did
      not prevent ulcer development.

PMID- 9160029
TI  - Influence of ablation plume dynamics on the formation of central islands in
      excimer laser photorefractive keratectomy.
AB  - PURPOSE: The aim of this study was to understand the dynamics of ablation
      products during excimer laser photorefractive keratectomy, and their influence on
      the formation of central islands. METHOD: Laser flash photography was used to
      investigate the dynamics of ablation products during photorefractive keratectomy.
      The ablation plume over polymethyl methacrylate (PMMA) and porcine cornea targets
      ablated with different zone diameters was imaged at various times between 10
      musec and 100 msec after the ablating laser pulse. On PMMA targets, the profiles
      of the resulting ablation craters were measured. RESULTS: In all cases, the
      ablation products formed a ring vortex. The plume velocities on cornea were found
      to be approximately twice as fast as on PMMA for all zone diameters. For both
      materials, the ablation plume evolves faster for smaller zone diameters. Central
      islands were observed for zone diameters between 1 and 7 mm on PMMA substrates.
      The islands became more pronounced with increasing zone diameter. CONCLUSIONS: A
      major cause for the formation of central islands was found to be particle
      redeposition at the center of the ablation zone. Because of the vortex dynamics,
      redeposition of particles favorably occurs at the center of the ablation zone.
      Additionally, the dynamics of the ablation plume lead to a concentration of
      airborne particles over the center of the ablation zone, which also may
      contribute to the creation of central islands by partial absorption of the next
      excimer laser pulse.

PMID- 9160030
TI  - Corneal shape changes after scleral buckling surgery.
AB  - PURPOSE: A prospective study was conducted to investigate the corneal shape
      changes due to scleral buckling surgery. These changes were analyzed based on the
      type of buckling procedures performed. METHODS: A total of 89 eyes from 88
      patients were stratified into four groups based on the type of buckling
      procedures used, including:group A, local buckling; group B, encircling; group C,
      encircling with vitrectomy; and group D, encircling with additional segmental
      buckling. These eyes underwent keratometry and videokeratography examinations
      before surgery as well as at 1, 3, and 6 months after surgery. RESULTS: No
      statistical significance was observed in the amounts of the induced corneal
      astigmatism and the refractive cylinder among the four groups. After local or
      segmental buckling (groups A and D), corneal steepening, which corresponded to
      the buckle, occurred at a high incidence. After encircling (groups B and C),
      either peripheral corneal flattening with focal central steepening or flattening
      on one side with coupled steepening on the opposite side was observed. Such
      corneal changes persisted for up to 6 months in an irregular and asymmetric
      configuration. CONCLUSIONS: All four types of circumferential scleral buckling
      surgery were found to produce prolonged irregular and asymmetric corneal shape
      changes, whereas the patterns of the changes differed depending on the buckling
      procedures used.

PMID- 9160031
TI  - Combination intravenous ceftazidime and aminoglycosides in the treatment of
      pseudomonal scleritis.
AB  - BACKGROUND: Pseudomonal scleritis is a serious and potentially blinding infection
      that usually is resistant to medical management. METHODS: Results for three
      patients with pseudomonal scleritis who were treated with both topical anti
      infectives and a combination of intravenous ceftazidime and aminoglycoside are
      presented in this case series. RESULTS: All three patients had a rapid response
      to the addition of combination intravenous drug therapy to topical therapy;
      eradication of the infection and healing of the ocular surface occurred within 8
      weeks. Only one patient, in whom cystoid macular edema developed, lost useful
      vision as a result of the infection. CONCLUSIONS: Combination therapy with
      intravenous ceftazidime and aminoglycoside may be more effective than single
      intravenous agents when used in addition to topical antibiotics and may obviate
      the need for adjunctive surgical procedures, such ascryotherapy, surgical
      extirpation, or conjunctival recession.

PMID- 9160032
TI  - Intraoperative mitomycin in primary pterygium excision. A prospective, randomized
      trial.
AB  - PURPOSE: Conjunctival autograft transplantation and postoperative mitomycin
      therapy are two adjuvant treatment methods shown to lessen the high pterygium
      recurrence rate seen with simple excision alone. The authors conducted a
      prospective, randomized study comparing these two techniques with a relatively
      new treatment method using intraoperative mitomycin application. METHODS: Fifty
      patients with 56 primary pterygia were randomized to 1 of 3 treatment groups:
      conjunctival autograft (group 1), postoperative mitomycin 0.2 mg/ml four times a
      day x 7 days (group 2), and intraoperative mitomycin 0.4 mg/ml x 3 minutes (group
      3). The mean follow-up time was 16 months (range, 6 to 28 months). RESULTS:
      Recurrences developed in 4 (22.2%) of 18 eyes in group 1, 4 (21.1%) of 19 eyes in
      group 2, and 2 (10.5%) of 19 eyes in group 3. Complications developed in two,
      patients from group 2, scleral thinning managed successfully with a scleral patch
      graft, and epithelial toxicity that resolved on discontinuation of mitomycin on
      postoperative day 6. There were no complications in the other two groups.
      CONCLUSIONS: Intraoperative mitomycin is a simple and effective alternative to
      postoperative mitomycin therapy, showing the lowest recurrence rate in their
      series with no toxicity during the study period. If the decision is made to use
      adjunctive mitomycin, the authors recommend intraoperative application over
      postoperative administration.

PMID- 9160033
TI  - Efficacy of lodoxamide eye drops on mast cells and eosinophils after allergen
      challenge in allergic conjunctivitis.
AB  - PURPOSE: The purpose of the study is to evaluate in a double-blind, randomized
      study the efficacy of lodoxamide tromethamine 0.1% versus placebo. METHODS: Signs
      and symptoms, tear tryptase, and tear fluid cytology were evaluated in 20
      asymptomatic subjects with allergic conjunctivitis. The study included three
      allergen challenges in skin test-positive patients. At the first visit, a
      threshold dose of allergen was established. At the second visit, a bilateral
      ocular challenge was performed without pretreatment. At the third visit, either
      lodoxamide or placebo eye drops were used for 1 week before ocular challenge.
      RESULTS: Lodoxamide significantly reduced tryptase levels (P < 0.01), neutrophils
      (P < 0.04), and eosinophils (P < 0.01) in the tear fluid and significantly
      inhibited ocular itching (P < 0.02) when compared with that of placebo.
      CONCLUSIONS: Lodoxamide is effective in reducing tryptase levels and the
      recruitment of inflammatory cells in the tear fluid after allergen challenge.

PMID- 9160034
TI  - Progressive visual loss from giant cell arteritis despite high-dose intravenous
      methylprednisolone.
AB  - BACKGROUND: Giant cell arteritis (GCA) often presents with devastating visual
      loss in the elderly, yet the ideal treatment is unknown. The disease most often
      has been treated with oral prednisone, although recently the use of the high-dose
      intravenous methylprednisolone (IVMP) has been reported to enhance visual
      recovery. METHODS: The authors reviewed patient charts from two university-based
      neuroophthalmology services and reviewed all previously reported cases of GCA
      treated with IVMP. RESULTS: Four patients with GCA exhibited severe, progressive
      visual loss after at least 48 hours of high-dose IVMP. A fifth patient had
      further visual loss in one eye and improvement in the other eye after 24 hours of
      IVMP. In previous reports of IVMP treatment in GCA, four patients lost vision and
      14 patients recovered vision. The authors review the details of these reports.
      CONCLUSIONS: The results of IVMP treatment of patients with visual loss from GCA
      are similar to the results of treatment with oral corticosteroids, with IVMP
      treatment being more costly and having a small risk of sudden death. The optimal
      dosage and route of corticosteroid treatment for GCA with visual loss remain
      elusive and warrant a treatment trial.

PMID- 9160035
TI  - Ocular ischemic syndrome.
AB  - PURPOSE: The purpose of the study is to investigate the clinical features and
      management of ocular ischemic syndrome (OIS) and factors influencing its
      development. INTERVENTION: The following interventions were used: detailed
      medical and ocular histories, complete ophthalmic evaluation including
      fluorescein angiography, internal carotid artery evaluation by duplex
      ultrasonography, and/or aortic arch angiography, management, and follow-up. MAIN
      OUTCOME MEASURES: The following outcome measures were considered: visual acuity,
      visual fields, intraocular pressure, anterior segment neovascularization and
      other abnormalities, lens, optic disc, retinal and choroidal changes, carotid
      artery stenosis or occlusion, diabetes mellitus, arterial hypertension, coronary
      artery disease, and cerebrovascular disease. RESULTS: Mean age of the 32 patients
      (39 eyes) with OIS was 68 +/- 8 years. Presenting visual symptoms included
      amaurosis fugax (15%) and/or gradual (28%) or sudden (41%) visual loss. At
      initial visit, eyes with OIS had visual acuity less than or equal to 20/400 in
      64%, iris neovascularization (NV) in 87%, angle NV in 59%, intraocular pressure
      from 4 to 60 mmHg (median 18 mmHg), optic disc pale (40%) and/or cupped (19%) or
      edematous (8%), disc NV (13%), retinal NV (3%), marked retinal circulatory stasis
      (21%), and retinal hemorrhages (24%). Associated systemic diseases in these
      patients included diabetes mellitus (56%), arterial hypertension (50%), coronary
      artery disease (38%), and previous stroke or transient ischemic attack (31%); the
      incidence of diabetes, coronary artery disease, and cerebrovascular disease was
      much higher in patients with OIS than in the comparable general population,
      especially that of diabetes. Occlusion or severe stenosis (80%-99%) of the
      internal carotid artery was seen in 74% on the side of OIS. CONCLUSIONS: Ocular
      ischemic syndrome has a poor visual prognosis. However, the ophthalmologist's
      diagnosis may be crucial to the health of these patients, because OIS may be the
      presenting sign of serious cerebrovascular and ischemic heart diseases.

PMID- 9160036
TI  - Blepharospasm and hemifacial spasm. Randomized trial to determine the most
      appropriate location for botulinum toxin injections.
AB  - PURPOSE: The purpose of the study is to analyze the effectiveness and side
      effects of botulinum toxin using four different treatment site applications to
      determine the most successful treatment regime with the least side effects.
      METHODS: In a prospective trial, 92 patients (50 blepharospasm and 42 hemifacial
      spasm) were assigned randomly to 1 of 4 different treatment groups (standard [S],
      brow [B], inner orbital [IO], or outer orbital [OO]). Each treatment group had a
      different pattern of injection sites in the orbicularis. A total of 285
      treatments were given, and the mean follow-up time was 16.4 months. RESULTS: In
      the blepharospasm group, patients assigned to the standard group had a
      significantly longer duration of effect than for those in the brow, inner
      orbital, and outer orbital groups (8.1 weeks compared with 4.5, 4.2, and 3.1
      weeks, respectively; P < 0.001). In the hemifacial spasm group, patients in the
      outer orbital group had significantly shorter duration of effect than those in
      standard, brow, or inner orbital group (7.2 weeks compared with 12.6, 12.8 and
      10.4 weeks, respectively; P < 0.001). The four major complications of botulinum
      toxin treatment were epiphora, ocular irritation, ptosis, and diplopia. The inner
      orbital treatment produced significantly more episodes of ptosis (13% of
      treatments). However, the standard treatment produced the most epiphora and
      ocular irritation (18% of treatments). CONCLUSIONS: The position of the injection
      sites around the orbicularis influences the effectiveness and side effects of
      botulinum toxin treatment for patients with blepharospasm and hemifacial spasm.
      The further the treatment is away from the eyelid margin, the lower the risk of
      ocular side effects. The standard treatment produces the longest duration of
      effect in the blepharospasm group but with the most transient ocular irritation
      and epiphora. In the hemifacial spasm group, the brow treatment has an equally
      long duration of effect as that of the standard treatment with fewer side
      effects.

PMID- 9160037
TI  - High resolution magnetic resonance imaging of neurovascular orbital anatomy.
AB  - PURPOSE: This study describes the magnetic resonance imaging (MRI) anatomy of the
      blood vessels and nerves of the orbit to provide a morphological basis for the
      interpretation of clinical findings. METHODS: Seven volunteers aged 29 to 54
      years underwent high-resolution MRI of the orbit on a 1 Tesla unit (Impact,
      Siemens, Germany). T1-weighted oblique-sagittal, coronal, and axial images were
      obtained using a surface coil. Anatomic structures on the magnetic resonance
      images were identified by comparison with corresponding histologic sections of
      the orbit. RESULTS: The ophthalmic artery and most of its branches (central
      retinal artery, posterior ciliary arteries, lacrimal artery, anterior and
      posterior ethmoidal arteries, supratrochlear artery, supraorbital artery, dorsal
      nasal artery) are visualized. The superior ophthalmic vein, the lacrimal vein,
      the medial ophthalmic vein, the inferior ophthalmic vein, the medial and lateral
      collateral veins, and the vorticose veins are also delineated. Furthermore,
      branches of the oculomotor nerve, the abducens nerve, the frontal nerve, the
      nasociliary nerve, the lacrimal nerve and the infraorbital nerve are identified
      in the magnetic resonance images. CONCLUSION: High-resolution MRI is capable of
      delineating the orbital arteries, veins, and nerves. This is mainly based on two
      principles. First, blood vessels appear mostly dark on magnetic resonance images
      because of the signal void of flowing blood. Second, the bright background of the
      orbital fat on T1-weighted magnetic resonance images accounts for the good soft
      tissue contrast in the orbit. With improved MRI technology and reduced imaging
      time, high-resolution-MRI may be applied routinely for diagnostic purposes.

PMID- 9160038
TI  - Ocular and orbital trauma from water balloon slingshots. A clinical,
      epidemiologic, and experimental study.
AB  - PURPOSE: The authors report the findings of 17 patients with ophthalmic injuries
      produced by launched water balloons; they determine water balloon kinetic
      energies in experimental and theoretical studies. METHODS: Six case summaries are
      presented; one case report was retrieved from the literature; ten injuries were
      reported to the Consumer Product Safety Commission. Energies were determined by
      field trials and calculations. RESULTS: Injuries included periorbital edema and
      ecchymoses, orbital contusions and hematomas, maxillary sinus hematomas, facial
      hypesthesia, eyelid lacerations, subconjunctival hemorrhages, corneal edema and
      abrasions, hyphemas, traumatic iritis, iris sphincter ruptures, iris atrophy,
      angle recession, iridodialysis, traumatic cataract, vitreous hemorrhages, retinal
      hemorrhages, macular hole formation, optic atrophy, and bony orbital wall
      fractures. Epidemiologic analysis revealed that children and young adults, more
      often males, were injured, most commonly in the warm weather months. In field
      trials, maximum water balloon velocities ranged from 38 to 41 m/sec (85-92 mph)
      with kinetic energies from 176 to 245 joules; by calculation, maximum velocities
      ranged from 42 to 54 m/sec (95-121 mph) with kinetic energies from 141 to 232
      joules. In a field demonstration, a slingshot-launched water balloon exploded a
      watermelon. CONCLUSION: Energies are comparable to or greater than those
      experienced with a variety of common objects, including some rifle bullets that
      are known to cause serious ophthalmic injuries. These energies are far in excess
      of those required to perforate a cornea, rupture a globe, or fracture the bony
      orbit. This study demonstrates the serious and potentially vision- and life
      threatening injuries inflicted by these "toys."

PMID- 9160039
TI  - Screening examination of premature infants for retinopathy of prematurity. A
      joint statement of the American Academy of Pediatric, the American Association
      for Pediatric Ophthalmology and Strabismus, and the American Academy of
      Ophthalmology.

PMID- 9160040
TI  - Cytokines involved in B-cell differentiation and their sites of action.
AB  - B cells originate from pluripotent hematopoietic stem cells and differentiate in
      the bone marrow into mature B cells. The differentiation of a stem cell into a
      mature B cell can be subdivided into five steps: early pro-B cells, late pro-B
      cell stage, pre-B cell stage, immature B cells, and mature B cells. Each
      differentiation step appears to be regulated by co-receptor and cytokines. The
      earliest B-cell progenitors are bound to the stromal cell surface by adhesive
      interactions through cell surface molecules to promote the binding of c-kit to
      stem cell factor (SCF). At the late pro-B cell stage, interleukin-7 (IL-7)
      induces proliferation and differentiation of pro-B cells to pre-B cells. Surface
      Ig-expressing mature B cells leave bone marrow and circulate into peripheral
      lymphoid organs in which they can be activated to proliferate and to
      differentiate into antibody-secreting cells by encountering antigens and "helper"
      T (TH) cells. TH cells activate B cells by their products, cytokines such as IL
      4, IL-5, and IL-6, and membrane-bound stimulatory molecules including CD40
      ligand. Each cytokine has pleiotropic activity on B cells and other cell types,
      and acts through a specific receptor. Abnormal expression of a cytokine receptor
      and aberrant signal transduction causes functional abnormality of B cells.

PMID- 9160041
TI  - Effect of aging on the gastrointestinal tract and the pancreas.
AB  - With estimates that about 14% of the U.S. population will be over 65 years old by
      the end of this century, scientific research has attempted to achieve a better
      understanding of the aging process and of diseases that are expressed in higher
      incidence with advancing age. Because of its high rate of cell turnover and
      continual renewal, the mucosa of the gastrointestinal (GI) tract appears
      particularly susceptible to age-related disruptions in the normal cell
      proliferative process. This may translate into altered function that may result
      in the induction of malnutrition or malabsorption of particular nutrients, or a
      greater incidence of GI diseases, such as neoplasia. This review will examine the
      evidence for age-related alterations in the structural and functional properties
      of different regions of the GI tract and the pancreas, and how they may relate to
      malnutrition or disease processes.

PMID- 9160042
TI  - Inherited disorders of glycoprotein synthesis: cell biological insights.
AB  - Disorders of glycoprotein synthesis have been described only recently, and few
      have been studied extensively at both the clinical and biochemical level. The
      identification and characterization of these rare diseases are important, not
      only for the patients and their families, but because they offer enormous insight
      into biological processes. For example, the targeting of acid hydrolases to
      lysosomes by mannose-6-phosphate was discovered as a direct result of the
      elucidation of the defect in I-cell disease. The notion of carbohydrates as
      targeting agents continues to have ramifications today, with the success of
      macrophage-targeted enzyme replacement therapy for Gaucher disease. Likewise,
      confirmation of the in vivo role of fucose-containing glycans and selectins in
      neutrophil function came from studies using specimens from patients with
      leucocyte adhesion deficiency type II due to reduced availability of GDP-fucose.
      Identification of the in vivo ligands of selectins also has implications for anti
      inflammatory therapies. Macular corneal dystrophy and spondyloepiphyseal
      dysplasia tarda offer an opportunity to investigate the number of different
      sulfotransferases in cells, their substrates, and their tissue expression. The
      Ehlers-Danlos progeroid variant offers insight into the function and regulation
      of the proteoglycan decorin, and suggests that several of the enzymes involved in
      proteoglycan synthesis may function as a multienzyme complex. The common
      occurrence of hypergonadotropic hypogonadism in patients with galactosemia or
      carbohydrate-deficient glycoprotein protein syndrome, due to defective N-linked
      glycosylation, suggests that ovarian function is particularly dependent on proper
      glycan-synthesis. A host of other concepts await discovery as a fuller contingent
      of human disorders of glycan synthesis achieves recognition.

PMID- 9160043
TI  - Comparison of somatostatin and pancreastatin on secretion of gastrin, pancreatic
      polypeptide, and peptide YY.
AB  - The purpose of this study was to compare the effects of pancreastatin (PST) (400
      pmol/kg/hr) and somatostatin (SRIF) (400 pmol/kg/hr) on food-induced release of
      gastrin, pancreatic polypeptide (PP), and peptide YY (PYY) in conscious dogs. The
      present findings indicate that SRIF is more potent than PST on the inhibition of
      food-induced release of PP; that SRIF and PST do not influence food-induced
      release of gastrin; and that PST cannot inhibit food-induced release of PYY,
      whereas SRIF inhibits PYY release in a potent fashion.

PMID- 9160044
TI  - Metabolic and structural effects of insulin-like growth factor-I and high-protein
      diet on dystrophic hamster skeletal muscle.
AB  - In muscular dystrophy (MD) there is an imbalance between muscle protein synthesis
      and protein degradation, which results in a net muscle catabolism, along with
      muscle wasting and weakness. Using a dystrophic hamster model (BIO 53.58), we
      examined the chronic (8 weeks) effects of two factors that may enhance muscle
      protein synthesis and inhibit protein degradation, namely, insulin-like growth
      factor-I (rhIGF-I) and high-protein diet (HPD). Protein synthesis was determined
      by measuring the incorporation of 14C phenylalanine into perfused leg muscle,
      while protein degradation was calculated from the release of tyrosine from the
      same perfused muscle. Urinary 3-methylhistidine excretion was used as an
      indicator of myofibrillar degradation. Treatment of dystrophic hamsters with
      rhIGF-I, HPD, or a combination of the two for 8 weeks resulted in significant
      decreases in total and myofibrillar degradation when compared with untreated
      dystrophic animals (P < 0.05) but had minimal effects on protein synthesis.
      Significant morphologic improvements (P < 0.05), including a normalization and
      greater uniformity of muscle fibers, were also seen in rhIGF-I- and rhIGF-I + HPD
      treated animals. rhIGF-I and HPD were effective in reducing the excessive
      proteolysis seen in dystrophic muscle, and this reduced proteolysis resulted in
      improvement of muscle morphology.

PMID- 9160045
TI  - Effects of norepinephrine infusion and exercise on blood pressure in rats.
AB  - Two experiments were conducted to test the hypotheses that norepinephrine (NE)
      infusion would increase blood pressure and wheel running activity level, and,
      secondly, that voluntary exercise would lower NE-induced increases in blood
      pressure. NE-bitartrate was infused into male Sprague-Dawley rats using an
      implanted osmotic pump (3.75 micrograms/kg/min in 0.9% saline). Control rats
      received the vehicle solution. Systolic blood pressure was measured by the tail
      cuff method. Voluntary wheel running activity expressed as wheel revolutions per
      24 hr was measured on the 5th, 9th, and 13th day. Blood pressure on the 13th day
      and wheel running activity on the 9th day were significantly higher in NE-infused
      rats. The NE content of heart tissue was not altered, but urinary excretion of NE
      and epinephrine was increased in the NE-infused animals. Food intake, body weight
      gain, and kidney weight per 100 g body wt were not changed but heart weight per
      100 g body wt was increased by NE infusion. Urinary total calcium excretion was
      higher in the NE-infused rats. Spontaneous voluntary exercise in running wheels
      attenuated increases of blood pressure in NE-infused rats. The results of the
      present study suggest that rats receiving exogenous NE exhibit increased blood
      pressure and voluntary wheel running activity. Voluntary wheel running exercise
      also reduces blood pressure in NE-infused rats.

PMID- 9160046
TI  - Endocytosis of serum albumin in regenerating rat liver.
AB  - Lysosomes, isolated from rat liver after 70% partial hepatectomy (PHX), were
      found, by Western blotting, to contain a considerable amount of serum albumin.
      The level of intralysosomal serum albumin after PHX showed biphasic patterns: it
      increased immediately after PHX, peaked at 30 min, rapidly declined within a few
      hours, rose again with a peak at 15 hr, and gradually declined thereafter. At 15
      hr after PHX, the content of lysosomal proteins in the liver increased to twice
      the level of unoperated control, and the electron-microscopic observation of the
      isolated lysosomes revealed numerous large membrane-delimited structures with
      ground substances of variable electron opacities. The increase in the
      intralysosomal serum albumin at 30 min and 15 hr was accompanied by changes in
      the buoyant densities of endosomes in Percoll density gradients. At both time
      points, the density profiles of endosomes isolated from hepatectomized rats
      shifted to the denser direction, suggesting that PHX activates fusion and/or
      maturation of endosomes. Formaldehyde-treated bovine serum albumin is known to be
      taken up by the liver by receptor-mediated endocytosis. The uptake of the
      modified heterologous albumin was shown to be activated as early as 30 min after
      PHX. Both the uptake of serum albumin into lysosomes and the shift of buoyant
      density profile of endosomes after PHX were inhibited by the administration of
      adrenergic receptor antagonists, particularly by the alpha r-antagonist prazosin.
      Further, the concentration of catecholamines in rat serum, particularly that of
      norepinephrine, was found to increase immediately after PHX, relative to that in
      serum from sham-operated rats. These results suggest that the elevation of serum
      norepinephrine levels after PHX activates endocytosis and facilitates delivery of
      endocytosed serum albumin to lysosomes, where albumin is digested to yield amino
      acids for possible use in protein synthesis during liver regeneration.

PMID- 9160047
TI  - Molecular cloning of the cDNA for rat hepatic, bile salt-dependent cholesteryl
      ester/retinyl ester hydrolase demonstrates identity with pancreatic carboxylester
      lipase.
AB  - Rat liver homogenates contain a neutral lipid ester hydrolase that requires
      millimolar concentrations of bile salts for maximal activity in catalyzing the
      hydrolysis of cholesteryl esters and retinyl esters in vitro. Previous studies
      have demonstrated that this hepatic hydrolase resembles rat pancreatic
      carboxylester lipase because it reacts with a specific pancreatic carboxylester
      lipase antibody and the eight N-terminal amino acids of the hepatic protein are
      identical to those of the pancreatic enzyme. Nonetheless, the exact molecular
      relationship between the hepatic and pancreatic enzymes is unclear. In the
      present study, a rat hepatic cDNA encoding the enzyme was cloned. Sequence
      analysis demonstrated that this cDNA corresponds to the full-length mature
      pancreatic carboxylester lipase (EC# 3.1.1.13). In individual animals the hepatic
      and pancreatic cDNA sequences were identical. However, among rats there were
      sequence variations, suggesting a polymorphic nature for this rat gene.

PMID- 9160048
TI  - alpha-difluoromethylornithine modifies gonadotropin-releasing hormone release and
      follicle-stimulating hormone secretion in the immature female rat.
AB  - Polyamines play an essential role in tissue growth and differentiation, in body
      weight increment, in brain organization, and in the molecular mechanisms of
      hormonal action, intracellular signaling, and cell-to-cell communication. In a
      previous study, inhibition of their synthesis by alpha-difluoromethylornithine
      (DFMO), a specific and irreversible inhibitor of ornithine decarboxylase, during
      development in female rats, was followed by prolonged high follicle-stimulating
      hormone (FSH) serum level and a delayed puberty onset. Those changes were
      relatively independent of body mass and did not impair posterior fertility. The
      present work studies the mechanisms and site of action of polyamine participation
      in FSH secretion during development. DFMO was injected in female rats between
      Days 1 and 9 on alternate days. At 10 days of age, hypothalami from control and
      DFMO rats were perifused in vitro, and basal and potassium-induced gonadotropin
      releasing hormone (GnRH) release were measured. The response to membrane
      depolarization was altered in DFMO hypothalami. Increased GnRH release in
      response to a low K+ concentration was evidenced. Adenohypophyses of the same
      treated prepubertal rats were perifused in vitro and the response to GnRH pulses
      was checked. In DFMO-treated rats, higher FSH release was observed, with no
      changes in LH or PRL secretion. Finally, pituitary GnRH receptor number in
      adenohypophyseal membranes from treated and control groups was quantified. A
      significant reduction in specific binding was evident in hypophyses from DFMO
      treated rats when compared with binding in the control group. In summary, DFMO
      treatment in a critical developmental period in the female rat impacts the
      immature GnRH neuronal network and immature gonadotropes. A delay in maturation
      is evidenced by a higher sensitivity to secretagogs in both pituitary glands and
      hypothalamic explants. These events could explain the prolonged high FSH serum
      levels and delayed puberty onset seen in this experimental model.

PMID- 9160049
TI  - Differential tyrosyl-phosphorylation of multiple mitogen-activated protein kinase
      isoforms in response to prolactin in Nb2 lymphoma cells.
AB  - Prolactin (PRL) stimulates mitogenesis and differentiative processes in a variety
      of cell types. Not all of the molecules involved in PRL signaling, which follows
      an initial PRL-receptor interaction, have been identified. In the present
      studies, PRL is shown to stimulate the differential tyrosyl phosphorylation of
      three isoforms (ERK-1, 2, and 4) of mitogen-activated protein kinases (MAP
      kinase) in a rat pre-T lymphoma cell line (Nb2). Evidence also suggests that PRL
      stimulates the tyrosyl phosphorylation of ERK-3, a MAP kinase isoform recently
      identified. When G1-arrested Nb2 cells are treated with 50 ng/ml oPRL, ERK-1
      through 3 become tyrosyl phosphorylated within minutes (an indication of enzyme
      activation) and then become dephosphorylated within 30 min. Conversely, ERK-4 is
      rapidly tyrosyl phosphorylated by 5 min, and remains in this state for at least 1
      hr.

PMID- 9160050
TI  - Sickle cell anemia.

PMID- 9160053
TI  - Asthma. The states' challenge.
AB  - At the national level, asthma is increasingly being recognized as an important
      public health problem. Because of the significant role of environmental exposure
      in asthma morbidity, public health agencies have a critical role to play in the
      surveillance and prevention of the disease. In April 1996, the Council of State
      and Territorial Epidemiologists, with assistance from the Centers for Disease
      Control and Prevention, surveyed state and territorial public health departments
      to determine the status of their asthma surveillance and intervention programs.
      Of the 51 health departments that responded, only eight reported that they had
      implemented an asthma control program within the previous 10 years. Reasons cited
      for not having programs included lack of funds, shortage of personnel, and asthma
      not being a priority. Most states were unable to assess the burden of asthma
      because they lack data or face barriers to using existing data. Removing barriers
      to the use of data is a first step toward defining the scope of the asthma
      problem.

PMID- 9160054
TI  - Use of a customer satisfaction survey by health care regulators: a tool for total
      quality management.
AB  - OBJECTIVES: To conduct a survey of health care providers to determine the quality
      of service provided by the staff of a regulatory agency; to collect information
      on provider needs and expectations; to identify perceived and potential problems
      that need improvement; and to make changes to improve regulatory services.
      METHODS: The authors surveyed health care providers using a customer satisfaction
      questionnaire developed in collaboration with a group of providers and a research
      consultant. The questionnaire contained 20 declarative statements that fell into
      six quality domains: proficiency, judgment, responsiveness, communication,
      accommodation, and relevance. A 10% level of dissatisfaction was used as the
      acceptable performance standard. RESULTS: The survey was mailed to 324 hospitals,
      nursing homes, home care agencies, hospices, ambulatory care centers, and health
      maintenance organizations. Fifty-six percent of provider agencies responded; more
      than half had written comments. The three highest levels of customer satisfaction
      were in courtesy of regulatory staff (90%), efficient use of onsite time (84%),
      and respect for provider employees (83%). The three lowest levels of satisfaction
      were in the judgment domain; only 44% felt that there was consistency among
      regulatory staff in the interpretation of regulations, only 45% felt that
      interpretations of regulations were flexible and reasonable, and only 49% felt
      that regulations were applied objectively. Nine of 20 quality indicators had
      dissatisfaction ratings of more than 10%; these were considered priorities for
      improvement. CONCLUSIONS: Responses to the survey identified a number of specific
      areas of concern; these findings are being incorporated into the continuous
      quality improvement program of the office.

PMID- 9160055
TI  - Comparing the smoking behavior of veterans and nonveterans.
AB  - OBJECTIVES: The authors analyzed self-reported questionnaire data from the 1987
      National Medical Expenditure Survey (NMES) to determine the smoking patterns of
      veterans. METHODS: Using NMES data, the authors compared veterans versus
      nonveterans overall, women veterans versus women nonveterans, Vietnam-era
      veterans versus other veterans, and veterans whose usual source of medical care
      was the Department of Veterans Affairs (VA) system versus veterans who received
      care elsewhere. RESULTS: The likelihood of ever having smoked cigarettes was
      higher for veterans than for nonveterans and for women veterans than for women
      nonveterans. The prevalence of current smoking was higher for veterans than for
      nonveterans and higher for those seeking care within the VA system than for other
      veterans. CONCLUSIONS: Given the enormous health care costs associated with
      smoking, health promotion efforts should be developed to reduce the high rate of
      smoking among veterans--especially those who are consumers of VA health care.

PMID- 9160056
TI  - A national physician workforce policy.

PMID- 9160057
TI  - The impact of managed care on the physician marketplace.
AB  - OBJECTIVE: To examine the impact of managed care on the employment and
      compensation of primary care and specialty physicians, as measured by changes in
      income, physician-to-population ratios, and specialty choices. METHODS: The
      authors used data from the American Medical Association's Socioeconomic
      Monitoring System survey, a nationally representative 1% random survey of post
      residency patient-care physicians, and location data from the AMA Masterfile to
      evaluate the relationship between the growth in managed care from 1985 to 1993
      and (a) inflation-adjusted physician incomes and (b) physician-to-population
      ratios for primary care physicians and specialists. They also used data from the
      National Residency Matching Program for 1989 through 1995 to look at trends in
      available positions and specialty choices. RESULTS: Primary care incomes grew
      4.78% annually ($33,526 cumulatively) in states with the highest managed care
      growth, compared to 1.20% ($7448 cumulatively) in the lowest quartile of managed
      care growth. The difference in income growth for medical and surgical
      subspecialists between the highest and lowest quartiles was not statistically
      significant. The incomes of radiologists, anesthesiologists, and pathologists
      (RAPs) rose 0.14%, or $1700, in the highest quartile versus 4.14% ($58,558) in
      the lowest. Subspecialists per capita did not differ by quartile of managed care
      growth; but RAPs per capita increased fastest in states in the lowest quartile.
      Between 1989 and 1995, the number of family practice and pediatric residency
      positions that were filled rose 32%, while the number filled remained stable for
      medical and surgical subspecialists and the number of RAP positions filled fell
      14%. CONCLUSIONS: The growth in managed care has been associated with significant
      changes in physician incomes and practice locations. Between 1985 and 1993,
      states with the fastest growth in managed care penetration saw the highest rate
      of growth in primary care physicians' income and the slowest rate of growth in
      RAP physicians' income. At the same time, the number of RAP physicians grew most
      rapidly in those states with the lowest rate of managed care growth. Finally,
      between 1989 and 1995, there was a dramatic increase in the number of primary
      care residency positions filled and a marked decrease in the number of RAP
      residency positions filled across the country.

PMID- 9160058
TI  - Downsizing the physician workforce.
AB  - OBJECTIVE: To estimate the need for downsizing the physician workforce in a
      changing health care environment. METHODS: First assuming that 1993 physician-to
      population ratios would be maintained, the authors derived downsizing estimates
      by determining the annual growth in the supply of specialists necessary to
      maintain these ratios (sum of losses from death and retirement plus increase
      necessary to parallel population growth) and compared them with an estimate of
      the number of new physicians being produced (average annual number of board
      certificates issued between 1990 and 1994). Then, assuming that workforce needs
      would change in a system increasingly dominated by managed care, the authors
      estimated specialty-specific downsizing needs for a managed care dominated
      environment using data from several sources. RESULTS: To maintain the 1993 199.6
      active physicians per 100,000 population ratio, 14,644 new physicians would be
      needed each year. Given that an average of 20,655 physicians were certified each
      year between 1990 and 1994, at least 6011 fewer new physicians were needed
      annually to maintain 1993 levels. To maintain the 132.2 ratio of active non
      primary care physicians per 100,000 population, the system needed to produce 9698
      non-primary care physicians per year, because an average of 14,527 new non
      primary care physicians entered the workforce between 1990 and 1994, downsizing
      by 4829, or 33%, was needed. To maintain the 66.8 active primary care physicians
      per 100,000 population ratio, 4946 new primary care physicians were needed per
      year, since primary care averaged 6128 new certifications per year, a downsizing
      of 1182, or 20% was indicated. Only family practice, neurosurgery,
      otolaryngology, and urology did not require downsizing. Seventeen medical and
      hospital-based specialties, including 7 of 10 internal medicine subspecialties,
      needed downsizing by at least 40%. Less downsizing in general was needed in the
      surgical specialties and in psychiatry. A managed care dominated-system would
      call for greater downsizing in most of the non-primary care specialties.
      CONCLUSION: These data support the need for downsizing the nation's physician
      supply, especially in the internal medicine subspecialties and hospital support
      specialties and to a lesser extent among surgeons and primary care physicians.

PMID- 9160059
TI  - Time to B. cereus about hot chocolate.
AB  - OBJECTIVE: To determine the cause of illnesses experienced by employees of a
      Minneapolis manufacturing plant after drinking hot chocolate bought from a
      vending machine and to explore the prevalence of similar vending machine-related
      illnesses. METHODS: The authors inspected the vending machines at the
      manufacturing plant where employees reported illnesses and at other locations in
      the city where hot chocolate beverages were sold in machines. Tests were
      performed on dry mix, water, and beverage samples and on machine parts. RESULTS:
      Laboratory analyses confirmed the presence of B. cereus in dispensed beverages at
      a concentration capable of causing illness (170,000 count/gm). In citywide
      testing of vending machines dispensing hot chocolate, 7 of the 39 licensed
      machines were found to be contaminated, with two contaminated machines having B.
      cereus levels capable of causing illness. CONCLUSIONS: Hot chocolate sold in
      vending machines may contain organisms capable of producing toxins that under
      favorable conditions, can induce illness. Such illnesses are likely to be
      underreported. Even low concentrations of B. cereus may be dangerous for
      vulnerable populations such as the aged or immunosuppressed. Periodic testing of
      vending machines is thus warranted. The relationship between cleaning practices
      and B. cereus contamination is an issue for further study.

PMID- 9160060
TI  - The early years of the PHS Narcotic Hospital at Lexington, Kentucky.

PMID- 9160061
TI  - Pharmacologic and dietary therapies in epilepsy: conventional treatments and
      recent advances.
AB  - A number of treatment options are currently available for the medical management
      of epilepsy. Conventional antiepileptic drugs (AEDs) include phenytoin,
      carbamazepine, valproic acid, ethosuximide, barbiturates, and benzodiazepines.
      Although these drugs control seizures, they may also cause blood dyscrasias,
      sedation, and cognitive impairment. Felbamate, gabapentin, lamotrigine, and
      vigabatrin are new AEDs believed to cause fewer side effects than conventional
      medications. Felbamate, however, has been linked with substantially increased
      incidence of aplastic anemia, and the other new AEDs have been studied for
      relatively short periods of time. Ketogenic diets, comprised of foods high in fat
      and low in protein and carbohydrate content, have been reported to improve
      seizure control. However, these diets are widely acknowledged to be unpalatable,
      making sustained compliance with dietary restrictions difficult. To promote long
      term control of seizures, physicians must consider the side effects of
      therapeutic interventions for epilepsy, as well as their anticonvulsant efficacy.

PMID- 9160062
TI  - Management of gallbladder polyps.
AB  - Polyps of the gallbladder are often incidentally identified during radiographic
      evaluation of abdominal pain. Once identified, they pose a dilemma with respect
      to their proper long-term management. Herein, polyps of the gallbladder are
      reviewed with specific attention to their management in light of their malignant
      potential. The available data suggest that polyps larger than 10 mm or that show
      rapid growth should be considered suggestive of malignancy, prompting
      cholecystectomy.

PMID- 9160064
TI  - Illness and injuries at summer camp.
AB  - Children at summer camp are at risk of injury and illness. The American Academy
      of Pediatrics and the American Camping Association have specific guidelines for
      the medical care of children in summer residential camps. This report describes
      the types of illnesses and injuries seen in 730 children attending camp for 2
      weeks, use of the infirmary, and difference in the onset of infectious diseases
      compared with injuries during the camp session. During the month studied, there
      were 921 infirmary visits. The most common diagnoses were injuries and infectious
      disease. Girls and boys were equally likely to be seen in the infirmary and had
      the same distribution of diagnoses. Infectious disease (gastroenteritis) had a
      later mean day of onset during the camp session than did injuries and was
      increasing in frequency at the end of each session. Potential common camp medical
      problems (sunburn, otitis externa) were prevented by simple medical preventive
      care.

PMID- 9160063
TI  - Left vagus nerve stimulation in children with refractory epilepsy: an update.
AB  - This report updates previous reports regarding the tolerance and efficacy of
      periodic vagus nerve stimulation in a group of 19 children with medically and
      surgically intractable epilepsy. After vagal stimulator implantation, follow-up
      continued from 2 months to 30 months, with the study period ending in October
      1995. Of the 19 patients, 6 (32%) had more than a 90% reduction in the number of
      monthly seizures, and 10 (53%) had more than a 50% reduction. Global evaluation
      scores indicated that only 1 patient had deterioration from baseline, 5 had no
      change, and the remainder had modest to remarkable improvement. All 3 children
      with unsuccessful corpuscallosotomy had improvement after implantation of the
      stimulator, and 5 of 6 children with Lennox-Gastaut syndrome had a 90% reduction
      of seizures. Five patients required fewer antiepileptic medications, and 1
      patient had an increase in medication. Adversities included 2 possible wound
      infections, 1 instance of generator failure, and hoarseness during stimulation in
      all patients. Changing stimulation parameters to increase the rate of stimulation
      and reduce the interval between stimulations resulted in improved seizure control
      in 4 of 5 patients. Periodic VNS was well tolerated by these children and may
      have a role in the management of refractory epilepsy.

PMID- 9160065
TI  - Can market-based solutions work for all of Medicare? Barriers to reform in the
      Medicare population residing in health professional shortage areas.
AB  - The proportion of the Medicare-eligible population living in health professional
      shortage areas (HPSAs), their demographics, and three health status indicators
      were examined in relationship to market-based reform proposals. Medicare-eligible
      residents of Georgia and Kentucky were classified as living in an HPSA (n =
      154,812) or non-HPSA (n = 556,602). Chi-squares were computed for demographic
      variables and health status indicators. A Mantel-Haenszel summary chi-square was
      computed after stratification of health status indicators by poverty level.
      Elderly residents of HPSAs accounted for 22% of the study population. Significant
      differences in all demographic variables except sex were detected. HPSA residents
      were more likely to have a mobility limitation, self-care limitation, or both a
      mobility and self-care limitation. Elderly residents in HPSAs are significantly
      more likely to have poorer health status and mobility limitations. Physician
      supply in HPSAs may be inadequate to support market-based reforms.

PMID- 9160066
TI  - Prenatal use of medications by women giving birth at a university hospital.
AB  - Medication use during pregnancy has changed over time because of various factors:
      new products have been marketed, concerns have arisen regarding safety and
      efficacy, public education has increased, and some prescription medications have
      been granted nonprescription status by the Food and Drug Administration. The
      purpose of this investigation was to determine overall medication and substance
      use by prenatal patients whose infants were delivered at our tertiary university
      hospital. Within 96 hours after delivery, 100 women were evaluated by a personal
      interview and medical record review. The medications most commonly used during
      pregnancy were vitamins, analgesics, calcium and iron preparations, and
      antibiotics. The mean numbers of medications consumed during the second and third
      trimesters (3.32 +/- 1.87 and 4.13 +/- 2.46) were significantly higher than the
      mean number taken before pregnancy (2.65 +/- 1.95). Over-the-counter medications
      accounted for 54% of the total products taken during pregnancy. Percentages of
      women using caffeine, tobacco, alcohol, and illicit drugs decreased during
      pregnancy.

PMID- 9160067
TI  - Enuresis in children with attention-deficit hyperactivity disorder.
AB  - We did a retrospective study of the prevalence of nocturnal and diurnal enuresis
      in patients with attention-deficit hyperactivity disorder (ADHD). Patients with
      ADHD were identified at a referral center for developmental pediatrics. Control
      patients were identified at a general pediatric and pediatric allergy clinic.
      Adjusting for differences in sex and current age, ADHD children at age 6 were 2.7
      times more likely than controls to have nocturnal enuresis and 4.5 times more
      likely to have diurnal enuresis. Results at children's current age were
      consistent with results at age 6; however, these differences were not
      statistically significant. Nocturnal and diurnal enuresis was found to be
      significantly more common in children with ADHD than in control subjects.
      Physicians who treat patients with ADHD should routinely inquire about the
      presence of enuresis.

PMID- 9160068
TI  - Systemic radionuclide therapy with strontium chloride Sr 89 for painful skeletal
      metastases in prostate and breast cancer.
AB  - Systemic radionuclide therapy with strontium chloride Sr 89 is a rediscovered
      alternative to relieve pain from bony metastases. Although numerous advances have
      been made in the diagnosis and treatment of cancer, pain remains a serious and
      debilitating disease complication. An increasing number of clinical trials are
      reporting satisfactory results with 89Sr-chloride therapy, now available for
      widespread clinical use. We have treated 11 patients with this radionuclide; of
      these patients, 8 had excellent to dramatic pain relief and 3 had mild to
      moderate improvement. Clinical response was based on subjective pain relief,
      increased mobility, decreased analgesic uptake, and/or improvement in daily
      activities, including work habits.

PMID- 9160069
TI  - Side effects of terazosin in the treatment of symptomatic benign prostatic
      hyperplasia.
AB  - In this report, we assess the safety of terazosin in the treatment of patients
      with symptomatic benign prostatic hyperplasia. We analyzed seven prospectively
      designed placebo-controlled trials involving 3,080 patients, 1,689 of whom
      received the study drug in doses ranging from 1 mg to 20 mg daily for a total of
      1,282 patient-years of exposure. The most common side effects seen in treated
      patients were dizziness (10.7%), asthenia (7.5%), and peripheral edema (4.0%).
      These side effects were generally reported as mild and improved after cessation
      of therapy. The incidence of withdrawal from the study due to side effects was
      14.5% in the treatment arm versus 11.4% in the placebo control arm. Also noted
      was a statistically significant decreased risk of urinary tract infection and
      myocardial infarction in the terazosin-treated group. This updated report
      confirms that terazosin can be administered safely to a population of men with
      symptomatic benign prostatic hyperplasia with minimal clinically significant side
      effects.

PMID- 9160070
TI  - Proposed algorithm to aid the diagnosis of cerebellopontine angle tumors.
AB  - Hearing and/or balance disorders are symptoms that may be associated with tumors
      of the cerebellopontine angle (CPA). Between March 1988 and May 1995, 22 patients
      had diagnosis or evaluation of CPA tumors at Cleveland Clinic Florida. The most
      common presenting signs or symptoms included unilateral low-frequency tinnitus,
      unsteadiness, and/or asymmetric hearing loss. On the basis of our experience, we
      have constructed an algorithm to help identify and manage acoustic nerve
      dysfunction. We compare our findings with national epidemiologic data and current
      medical reports.

PMID- 9160071
TI  - Clinical, radiographic, and pathologic features of medical calcific sclerosis in
      the breast.
AB  - Medial calcific sclerosis (MCS), a nonocclusive calcification of the media of
      small to medium-sized muscular arteries, may occur in the breast. To ascertain
      whether MCS causes difficulty with mammographic interpretation of breast
      calcifications and to determine its clinical and pathologic associations, we
      reviewed the records and biopsy specimens from 62 patients who had had screening
      mammography and breast biopsy, lumpectomy, or mastectomy. Ten specimens from 7
      patients showed MCS. Average age of patients without MCS was 48.8 years, and that
      of the 7 patients with MCS was 61.3 years. Microcalcifications were found in 25
      of 62 mammograms (34%). Of the 7 patients with MCS, 2 had hypertension, 1
      diabetes mellitus, 2 diabetes mellitus and hypertension, and 2 neither
      hypertension nor diabetes mellitus. In 5 specimens, calcification only was
      associated with MCS. In 2 of these specimens, the mammographic calcifications
      were thought to be suggestive of malignancy on the basis of clustering and
      spiculation. One of the 2 was benign on histopathology; the other was malignant.
      Overall, carcinoma was identified in 3 of 7 patients with MCS (compared with 11
      of 55 patients without MCS) and in 2 of 5 specimens (2 patients) with mammary MCS
      as the only type of calcification. The mammographic appearance of the
      microcalcification in MCS may suggest malignancy.

PMID- 9160073
TI  - Outpatient bowel preparation for elective colon resection.
AB  - To determine the safety and cost-effectiveness of outpatient preoperative bowel
      preparation with polyethylene glycol-electrolyte lavage solution, we
      retrospectively analyzed 726 cases of colectomy done by colon and rectal surgeons
      between July 1987 and July 1991. Included were 319 patients who had elective
      segmental or total abdominal colectomy with primary anastomosis. Patients who
      required protective proximal stoma were excluded. Patients requiring emergency
      surgery, colostomy closure, and restorative proctocolectomy were excluded.
      Patients were separated into two groups equally matched by age, sex, procedure
      done, and comorbidity: 145 had bowel preparation as outpatients and 174 as
      inpatients. Both groups had similar numbers of days hospitalized, days receiving
      nothing by mouth, and days requiring nasogastric intubation or gastrostomy tube,
      as well as similar postoperative complications. There was one wound infection,
      one anastomotic leak, and one death in each group. Cost of outpatient preparation
      was approximately $40. Cost of inpatient preparation, including a semiprivate
      room, was approximately $400. Outpatient preparation with polyethylene glycol
      electrolyte lavage solution and oral antibiotics before elective colon resection
      can be done with equivalent safety and at a substantial cost savings.

PMID- 9160072
TI  - Tongue protrusion dystonia: treatment with botulinum toxin.
AB  - We report the treatment experience in a series of patients with involuntary
      tongue protrusion resulting from oromandibular dystonia (OMD) or Meige's
      syndrome. A retrospective analysis of clinical findings and results of treatment
      was conducted on patients treated at Vanderbilt University Medical Center between
      1989 and 1995. After unsuccessful treatment with conventional oral medications,
      nine patients having involuntary tongue protrusion resulting from OMD or Meige's
      syndrome were treated with botulinum toxin type A (BTX-A) injected into the
      genioglossus muscle at four sites via a submandibular approach. A marked
      reduction in tongue protrusion was achieved in six patients (67%). Of 35
      consecutive injections, 83% were successful at reducing tongue protrusion. Mild
      dysphagia complicated 14% of the injections. The average dose injected was 34 (+/
      3) units producing a 15 (+/- 2) week average duration of effect. Injection of
      the genioglossus with BTX-A may prove to be a valid treatment option for
      involuntary tongue protrusion related to OMD or Meige's syndrome. A double-blind,
      placebo-controlled trial is needed to better define efficacy and adverse events.

PMID- 9160075
TI  - Wilson's disease.
AB  - We describe a patient who had severe neurologic symptoms, psychiatric
      abnormalities, and secondary amenorrhea superimposed on a history of hemolytic
      anemia and micronodular cirrhosis attributed to hemochromatosis. The correct
      diagnosis of Wilson's disease was delayed until the appearance of Kayser
      Fleischer rings and a low serum ceruloplasmin level. Appropriate treatment
      ameliorated symptoms, and maintenance therapy has been effective in retarding
      progression. It is essential to consider Wilson's disease in patients with
      unexplained hepatic, neurologic, and psychiatric dysfunction, because appropriate
      early medical treatment can prevent further organ damage and reduce the risk of
      permanent damage to the liver and brain.

PMID- 9160074
TI  - Survival benefits of pulmonary cellular activation in AIDS patients with
      Pneumocystis infection.
AB  - Pneumocystis carinii pneumonia (PCP) is the most common life-threatening,
      opportunistic infection in patients with acquired immunodeficiency syndrome.
      Between 1984 and 1987, patients infected with human immunodeficiency virus (HIV)
      received bronchoalveolar lavages to confirm PCP diagnosis. Unstained slides
      containing bronchoalveolar cells from 20 of these patients were stored. Eight
      years after the last diagnostic bronchoalveolar lavage, blinded investigators
      immunohistochemically analyzed the unstained bronchoalveolar cells for the
      presence of proliferating cells and pneumocystic cysts. A significant association
      was found between the percentage of activated macrophages and patient survival
      after diagnostic bronchoalveolar lavage. On chart review, patients with higher
      CD4/CD8 ratios had significantly greater alveolar macrophage activation. The
      correlation of life span and pulmonary cellular activation in these cases (most
      predating retroviral therapy) suggests the importance of pulmonary cellular
      function to immunity and survival in patients infected with HIV.

PMID- 9160076
TI  - Primary cardiac lymphoma: initial symptoms suggestive of gastrointestinal
      disease.
AB  - We report a case of primary cardiac lymphoma in a patient who was not infected
      with human immunodeficiency virus and had symptoms suggestive of upper
      gastrointestinal (GI) disease. Examination revealed no GI abnormalities.
      Echocardiography, prompted by sudden development of congestive heart failure,
      revealed a large right atrial mass. Cardiac biopsy followed by staging evaluation
      indicated primary cardiac non-Hodgkin's lymphoma. After chemotherapy was begun,
      the tumor shrunk and GI symptoms resolved, suggesting an etiologic relationship
      by a referred pain mechanism. Unusual features of our case include the initial
      predominance of GI symptoms and the circumstances that led to diagnosis
      antemortem. The case also underscores the importance of considering intrathoracic
      disease in patients with upper abdominal symptomatology.

PMID- 9160077
TI  - Vibrio fluvialis: an underrecognized enteric pathogen in infants?
AB  - We report a case of Vibrio fluvialis gastroenteritis in an infants 3 1/2 weeks
      old. The case was unusual because no likely epidemiologic risk factors were
      involved. Since several other such cases in young infants have been reported, V
      fluvialis should be considered in the differential diagnosis of infantile
      gastroenteritis.

PMID- 9160078
TI  - Rhabdomyolysis associated with simvastatin-gemfibrozil therapy.
AB  - Simvastatin is a potent inhibitor of hydroxymethylglutaryl coenzyme A (HMG-CoA)
      reductase intended for use as a hypocholesterolemic agent. The long-term clinical
      experience with simvastatin indicates that it is a safe, effective, and well
      tolerated hypolipidemic agent. Laboratory adverse events involving elevations of
      serum transaminase levels and serum creatine kinase (CK) levels to more than
      three times the upper limit of normal range have been seen in 1.5% and 3.4% of
      cases, respectively. We describe a case of severe myopathy and rhabdomyolysis
      associated with concomitant use of simvastatin and gemfibrozil. Seven days after
      discontinuing administration of gemfibrozil and simvastatin, the patient's
      condition improved and she was discharged home. Although this is the first report
      to indicate an association between myopathy and concomitant use of simvastatin
      and gemfibrozil, we strongly recommend caution and careful monitoring if
      simvastatin is given to patients receiving gemfibrozil.

PMID- 9160079
TI  - When exercise goes awry: exertional rhabdomyolysis.
AB  - Exertional rhabdomyolysis occurs when exercise, often of the eccentric type,
      damages myofibrils and sarcolemma, with release of the enzyme creatine kinase and
      pigmented myoglobin into the serum. Severe muscle soreness and dark urine are the
      hallmark symptoms, and renal failure may develop. Formerly a disease of military
      recruits, it is now seen more often in exercisers. Although a genetic trait may
      predispose, the illness probably can be avoided by common sense behavior such as
      a gradual increase in exercise intensity, proper hydration before, during, and
      after exercise, and avoiding exercise in extremely hot or humid environments.

PMID- 9160080
TI  - Angioedema associated with angiotensin II receptor antagonist losartan.
AB  - Angioedema has not been associated with losartan therapy in hemodialysis
      patients, as it has been with angiotensin converting enzyme (ACE) inhibitors. We
      report the case of a hemodialysis patient who previously had angioedema after
      therapy with ACE inhibitors and again had angioedema while taking losartan. We
      suggest caution in using losartan in patients with known sensitivity to ACE
      inhibitors manifested by angioedema.

PMID- 9160081
TI  - Cervical esophageal web caused by an inlet patch of gastric mucosa.
AB  - A 55-year-old woman had chronic, progressive dysphagia. An esophageal web in the
      cervical esophagus was identified by barium swallow and endoscopy. At endoscopy,
      an inlet patch of gastric mucosa was identified in proximity to the cervical web.
      It is believed that gastric acid production from the inlet patch led to
      development of the cervical esophageal web. We present our patient's case and
      review the literature relevant to this topic.

PMID- 9160082
TI  - Meperidine-induced generalized seizures with normal renal function.
AB  - Meperidine is a widely prescribed opioid analgesic used in a variety of clinical
      situations. The parent compound has central nervous system depressant effects.
      However, the sole active metabolite, normeperidine, is a central nervous system
      excitatory agent and has the ability to cause seizures, especially in patients
      with renal failure. Patients with normal renal function rarely manifest seizure
      activity when given meperidine, but if the drug is used in large doses at
      frequent dosing intervals, seizures may occur. Reported here is the case of a man
      with normal renal function who had a tonic-clonic seizure due to meperidine that
      was administered for the pain of underlying chronic pancreatitis.

PMID- 9160083
TI  - Anaplastic large cell lymphoma of T-cell phenotype in acquired immunodeficiency
      syndrome.
AB  - Anaplastic large cell lymphoma (ALCL) is an uncommon non-Hodgkin's lymphoma in
      the general population as well as in HIV-infected patients. Ordinarily, ALCL
      expresses T-cell phenotype, but lymphoproliferative disorders derived from T
      cells rarely occur in acquired immunodeficiency syndrome (AIDS). We describe a
      white male homosexual with AIDS who had bilateral pleural effusions. Examination
      of the pleural fluid revealed ALCL positive for Ki-1 (CD30), LCA (CD45), UCHL-1
      (CD45RO), CD43, CD3, and epithelial membrane antigen. The lymphoma was negative
      for the B-cell marker L26 (CD20) and for Leu-M1 (CD15). The T-cell origin was
      also confirmed by the monoclonal rearrangement of the T-cell receptor beta chain
      gene. A review of other cases of ALCL in HIV-positive individuals shows
      variability in clinical presentation and biologic behavior of this lymphoma type.
      It also points to the potential contribution of gene rearrangement studies for
      recognition of phenotype. In addition, the role of determination of the presence
      of t(2;5) and the corresponding gene product is discussed.

PMID- 9160084
TI  - Effects of age, sex, and initial presentation on the clinical course of Behcet's
      syndrome.

PMID- 9160085
TI  - Medical therapy for inflammatory bowel disease.

PMID- 9160086
TI  - Delayed posttraumatic tamponade.

PMID- 9160087
TI  - Immunoglobulin gene organization and the mechanism of repertoire development.
AB  - Recombinant DNA technology has made it possible to comparatively examine the
      immunoglobulin (Ig) gene constitution of numerous species. These studies reveal
      that many species diverge from the pattern seen in rodents and primates while
      revealing a number of interesting correlations involving Ig gene organization, B
      cell lymphogenesis and the mechanism of repertoire development; many of these
      fail to correlate with traditional phylogenetic relationships. These correlates
      pose new questions regarding repertoire developments, which suggest that
      considerable diversity exists in the process. These findings also allow new
      questions to emerge regarding the role of IgD, the size of the B-cell repertoire,
      and the role that antigen may or may not play in repertoire development. These
      issues are discussed with the intention of stimulating experimentation to test a
      number of speculative hypotheses regarding B-cell and repertoire development.

PMID- 9160088
TI  - MCA sarcomas induced in scid mice are more immunogenic than MCA sarcomas induced
      in congenic, immunocompetent mice.
AB  - With the aim of studying possible T-cell mediated selection of the cells in
      growing tumours, 108 mice of the C.B-17 strain, either immunocompetent C.B-17
      mice or histocompatible immunodeficient C.B-17 severe combined immune deficiency
      (scid) were treated with 3-methylcholanthrene (MCA) in two different dosages. A
      total of 51 tumours were obtained, 44 of which were established as uncloned
      tumour cell lines, and used for further study. Tumour incidence correlated with
      carcinogen-dosage in that more tumours developed in groups treated with a high
      MCA dose than in groups treated with a low MCA dose, but not with immune status
      of the tumour host. No significant difference in the level of MHC class I
      molecule expression was found between the two groups of tumours. The rate of
      rejection after transplantation to syngeneic immunocompetent hosts was
      significantly higher for the scid tumours than for the non-scid tumours. The
      authors suggest that this reflects an immunoselection performed by T cells in the
      immunocompetent host in which the tumour originated, which has eliminated highly
      immunogenic tumour cells, leaving non-immunogenic tumour cells to grow.

PMID- 9160089
TI  - Human leukaemic (HMC-1) and normal skin mast cells express beta 2-integrins:
      characterization of beta 2-integrins and ICAM-1 on HMC-1 cells.
AB  - Mast cells are bone marrow-derived, ubiquitous connective tissue resident cells.
      However, their mechanisms of migration, the distribution of immature and mature
      cells and their interaction with other inflammatory cells are largely
      unclarified. Possibly, beta 2-integrins play an important role in these
      processes. In the present investigation, the authors studied the expression and
      regulation of the beta 2-integrins LFA-1 (CD11a/CD18), Mac-1 (CD11b/CD18),
      p150,95 (CD11c/CD18) and of the LFA-1/Mac-1 counter-receptor intercellular
      adhesion molecule-1 (ICAM-1; CD54) on leukaemic (HMC-1 cell subclone 5C6) and on
      normal mature human skin mast cells. The HMC-1 cells clearly expressed CD11a,
      CD18 and CD54, while expression of CD11b and CD11c was low. The apparent
      molecular weights were 180 kDa (CD11a), 95 kDa (CD18) and 90 kDa (CD54) as
      determined by Western blot analysis. Phorbol myristate acetate (PMA) induced a
      time- and dose-dependent up-regulation of CD11a, CD11b, CD11c, CD18 and CD54 that
      was inhibited by cycloheximide, suggesting a dependence on de novo protein
      synthesis. Enhanced expression of CD11a, CD11b, CD11c and CD18 could also be
      confirmed at the gene level as demonstrated by semi-quantitative reverse
      transcription-polymerase chain reaction (RT-PCR). Increased expression of LFA
      1/ICAM-1 in response to PMA was accompanied by strong enhancement of homotypic
      cell aggregation, suggesting that newly synthesized LFA-1/ICAM-1 is functionally
      active. In order to determine a physiologically relevant way of mast cell beta 2
      integrin modulation, several cytokines and chemotactic mediators (interleukin-4,
      IL-4; nerve growth factor beta, NGF beta; C5a; and leukotriene B4, LTB4) were
      tested for their influence on adhesion molecule cell surface density. Only LTB4
      was shown specifically to up-regulate CD11a and CD18, but not CD11b or CD11c. The
      presence of CD11a, CD11c and CD18 could be confirmed on a low percentage of
      normal skin mast cells by immunofluorescence, using a double staining technique.
      In comparison to normal skin, a significantly higher percentage of CD18+ mast
      cells was found in inflammatory dermatoses such as psoriasis vulgaris, atopic
      dermatitis and lichen planus. Therefore, mast cell beta 2-integrins possibly play
      an important role during homing of immature mast cells as well as during the
      interaction of activated mast cells with other inflammatory cells.

PMID- 9160090
TI  - Kinetics and repertoire selection of T cells derived from the early waves of
      fetal thymus colonization after thymus grafting in allogeneic nude recipients.
AB  - The survival of T cells derived from the early waves of thymus colonization by
      haemopoietic cell precursors was investigated by grafting thymus from B6.Thy1.1
      day 14 embryos (E14) (first wave) or E17 or newborn thymus (subsequent waves)
      into allogeneic athymic BALB/c (Thy1.2) nude recipients. The survival of donor
      derived Thy1.1 cells was longer when they were derived from early thymocytes.
      Donor B6.Thy1.1 V beta 5 and V beta 11 T cells, although maturing in BALB/c host
      presenting Mls2a superantigens, were not deleted, in contrast to host Thy1.2 T
      cells differentiating from endogenous stem cells. These results show that the
      population of T cells derived from early precursors undergoes particular
      selection characteristics, which favour the inclusion of potentially autoreactive
      cells with prolonged survival, even in H-2 allogeneic conditions which normally
      do not allow the survival of peripheral T cells.

PMID- 9160091
TI  - Changes in arrangement and in conformation of molecular components of peripheral
      T-cell antigen receptor complex after ligand binding: analyses by co
      precipitation profiles.
AB  - Amounts of co-precipitating CD3 components by anti-T-cell receptor (TCR)V beta or
      anti-CD4/8 monoclonal antibodies were compared between non-stimulated and
      stimulated splenic T cells. The amounts of co-precipitating CD3 delta, epsilon
      and gamma chains with TCR alpha beta and with CD4/8 were not significantly
      changed after TCR ligation. The apparent amount of CD3 zeta chain co-precipitated
      with TCR alpha beta increased up to threefold, while the actual amount of co
      precipitating CD3 zeta with TCR alpha beta and the total amount of specifically
      precipitated CD3 zeta are not changed after cross linking of TCR. The apparent
      amount of CD3 zeta chain co-precipitated with CD4/8 also increased. Unlike co
      precipitation with TCR alpha beta, the actual amount of CD3 zeta co-precipitated
      with CD4/8 increased significantly. This observation suggests a conformational
      change as well as the relocation of CD3 zeta molecules within the TCR complex
      after the signal delivery. After TCR ligation, CD3 zeta chains relocate to the
      vicinity of either CD4 or CD8 molecules. In addition, when cross linking and
      binding signals are compared, CD3 chains undergo two distinct phases of
      conformational change. The responses, while the later conformational change
      caused by the cross linking of TCR does not induce but enhances the proliferative
      response.

PMID- 9160092
TI  - The effects of cyclosporin A on V(D)J recombination activity.
AB  - V(D)J recombination is up-regulated by the protein kinase A (PKA) pathway and
      down-regulated by the protein kinase C (PKC) and Ca2+ pathways. When activators
      of the PKA and PKC pathways or the PKA and Ca2+ pathways are given at the same
      time, a strong reduction of the PKA effect is observed. The V(D)J recombination
      suppressing effect of elevated intracellular Ca2+ levels, but not that of the PKC
      pathway, can be abrogated by the addition of the calcineurin inhibitor
      cyclosporin A (CsA), indicating that the effect of Ca2+ is mediated by
      calcineurin. This effect is observed in a pre B cell line as well as in the V(D)J
      recombination competent fibroblast cell line L4, indicating that the mechanisms
      of the cross talk between different signalling pathways are basically the same in
      both cell types. In the absence of Ca2+ mobilizer CsA increases the V(D)J
      recombination rate in pre B cells but not in L4 cells.

PMID- 9160093
TI  - Characterization of the delayed type hypersensitivity-inducing epitope of MPT64
      from Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis secretes several proteins into the extracellular
      environment, some of which are restricted to the M. tuberculosis complex. One of
      these antigens is MPT64. Recently, the authors showed that native as well as
      recombinant MPT64 is able to distinguish between an M. tuberculosis infection and
      a BCG Danish 1331 vaccination. Improved distinction between tuberculin purified
      protein derivative (PPD) sensitivity conferred by an M. tuberculosis infection
      and that induced by a BCG vaccination or infection with environmental
      mycobacteria would be useful in the control of tuberculosis. In this study, the
      authors report the mapping and characterization of a Dth-inducing epitope by the
      use of synthetic peptides in guinea-pigs vaccinated with BCG Danish 1331 or
      Tokyo. Studies with overlapping synthetic peptides have pinpointed the biological
      activity to a single Dth-inducing epitope at the carboxyterminal region of MPT64
      consisting of 15 residues between amino acids Gly-173 and Ala-187, the core
      epitope (CE15). A fine mapping using truncated versions of CE15 indicates the
      epitope is restricted to 13 residues between amino acids Val-174 to Glu-186.
      However, the optimal Dth reactivity is obtained by CE15. Different modifications
      of CE15 revealed that a lysine tree construction improves the skin reactivity to
      a maximum level approaching that of the reactivity to tuberculin PPD.

PMID- 9160094
TI  - HLA-DRB9--possible remnant of an ancient functional DRB subregion.
AB  - The DRB subregion of the HLA complex contains, in addition to the functional
      genes, a number of pseudogenes and gene fragments. Fourteen kilobases of DNA were
      sequenced from the segment upstream of the DRB9 gene fragment, as well as shorter
      segments from different HLA and corresponding ape haplotypes. The analysis of the
      sequences and restriction fragments indicates that the segment is a remnant of an
      ancient DRB subregion which may have been functional before the primate radiation
      and which later became the source of extant functional DRB genes in various
      primate groups, different ones in different groups. The remnant segment has
      remained constant in its organization for at least 4 million years. This
      constancy contrasts with the variability of the adjacent functional part of the
      DRB subregion occupied by the DRB1 and other loci. The constancy may be related
      to the monomorphism and evolutionary conservation of the DRA locus.

PMID- 9160095
TI  - Ex vivo PKH26-labelling of lymphocytes for studies of cell migration in vivo.
AB  - A prerequisite for studies of cell migration is that the cells of interest can be
      appropriately labelled and subsequently easily traced. The use of radioisotopes
      or fluorescent substances that bind covalently to the cell surface, e.g.
      fluorescein isothiocyanate (FITC) or rhodamine isothiocyanate (RITC), have
      limitations such as rapid loss of the labelling, toxicity and interference with
      cell surface molecules. In the present work the authors labelled rat spleen
      lymphocytes with the fluorescent labelling molecule PKH26, which is incorporated
      into the lipid bilayer of cytoplasmic membranes. The labelled lymphocytes were
      injected intravenously into syngeneic recipients and 2 or 6 days later the
      lymphocytes were detected in various organs by using flow cytometry and
      fluorescence microscopy. As could be expected, the lymphocytes homed to lymphoid
      tissues, preferably the spleen, and no labelled cells were found in non-lymphoid
      organs such as the heart and the kidney. Membrane labelling proved to be intense,
      uniform and stable and PKH26 positive cells were easily detectable in fractions
      less than 0.2% in peripheral blood and the various tissues after 6 days of in
      vivo circulation. Thus, the PKH26 dye appears to be suitable for labelling cell
      populations used in the study of cell migration in vivo, both under normal
      conditions and when specific immunological processes are taking place, such as
      graft rejection and tumour growth.

PMID- 9160096
TI  - Cutaneous delayed type hypersensitivity in SCID mice adoptively transferred with
      lymphocytes is B cell independent and H-2 restricted.
AB  - Severe combined immunodeficiency (SCID) mice are largely devoid of functional T
      and B lymphocytes but have normal antigen presenting cell (APC) capacity. The
      authors have examined the requirements for cutaneous delayed type
      hypersensitivity (DTH) in SCID recipients by i.p. transfer of freshly isolated
      naive mature. T cells or non-fractionated spleen cells of H-2 compatible or
      incompatible origin. Recipient SCID mice were epicutaneously sensitized with
      oxazolone (OXA) within 24 h after cell transfer. SCID mice injected with as few
      as 10(5) H-2 compatible BALB/c (H-2d) spleen cells were able to mount DTH ear
      swelling reaction upon sensitization and challenge with OXA. Non-fractionated
      spleen cells from H-2 incompatible B6 or NZW mice were also able to restore DTH
      capacity in SCID recipients. However, when thymocytes were transferred, only
      donor mice expressing H-2d, but not H-2b and H-2z, haplotype restored DTH
      reactivity. Serum levels of IgM and IgM anti-OXA antibodies in SCID mice 27 days
      post-transfer with 10(7) BALB/c spleen cells were similar to that of intact donor
      mice. In contrast, specific antibodies of IgG isotype were approximately only one
      tenth of that found in BALB/c controls. The results of this study show that for
      the development of cutaneous DTH, in SCID mice transferred with T cells, H-2
      restricted APC-T cell interaction is required, whereas B cells are not mandatory.
      Also, SCID mice transferred with splenocytes show signs of defect immunoglobulin
      switch function. The authors believe that this model of DTH will be useful in
      delineating the effects of immunomodulatory substances in vivo on distinct host
      versus donor cell populations.

PMID- 9160097
TI  - Induction of CD8+ CTL recognizing mycobacterial peptides.
AB  - Mycobacterium tuberculosis is the single, most important cause of morbidity
      attributable to a single infectious organism. CD8+ T cells play an important role
      in anti-tuberculous immune responses in both mice and humans. Data concerning the
      identity of mycobacterial antigens recognized by CD8+ T cells is limited;
      consequently, few CTL epitopes have been characterized. The authors identified
      allele-specific (H-2b and d) MHC class I binding motifs in six prominent M.
      tuberculosis protein antigens (the 19 and 38 kDa lipoglycoproteins and the 10,
      16, 65 and 70 kDa stress proteins). These predicted epitopes were tested for MHC
      binding as well as their ability to elicit peptide-specific CTL following in vivo
      priming. The authors were able to identify eight previously undescribed
      mycobacterial CTL epitopes by using spleen cells from peptide-immunized mice. In
      addition, CTL specific for at least one of these epitopes also recognized the
      naturally processed epitope presented on transfected EL4 target cells. These
      mycobacteria-derived CTL epitopes could be important for future analysis of the
      involvement of CD8+ T cells in M. tuberculosis infection, pathogenesis and
      vaccine development.

PMID- 9160098
TI  - MHC class I presentation of live and heat-inactivated Sendai virus antigen in
      T2Kb cells depends on an intracellular compartment with endosomal
      characteristics.
AB  - T2Kb cells, which do not express TAP1/2 peptide transporters or the low molecular
      weight protein 2/7 (LMP2/7) proteasomal subunits, can still process and present
      both live and heat-inactivated Sendai virus (SV). As this operation may also
      reflect the existence of an alternative processing pathway in normal antigen
      presenting cells (APC), the authors have characterized it using intracellular
      inhibitors and anti-Kb monoclonal antibodies (MoAbs). From the results with
      lipophilic amines (ammonium chloride, methylamine and chloroquine), cytoskeletal
      inhibitors (cytochalasin B and vinblastine), and an endoprotease inhibitor
      (phenylmethylsulfonyl fluoride, PMSF), the authors conclude that the processing
      of SV antigen in T2Kb cells has endosomal characteristics depending on cellular
      activities such as uptake, vesicular transport and intracellular-vesicular
      proteolysis. In addition, internalized 'empty' Kb molecules derived from the T2Kb
      cell surface appeared to be involved in the presentation of SV antigen, as
      demonstrated by a protocol using a combination of the Golgi inhibitor brefeldin
      A(BFA) and anti-Kb antibodies. The results thus indicate that T2Kb cells process
      SV antigen in an endosomal-like compartment which contain recycling 'empty' Kb
      molecules.

PMID- 9160099
TI  - RT-PCR topography of chronic psoriasis skin based on analysis of T-cell receptor
      B variable region gene usage.
AB  - Psoriasis is a hyperproliferative inflammatory disease and 70% of patients
      develop a chronic plaque form. The pathogenesis of psoriasis is not known but
      evidence exists that T cells play a crucial role. The T cell V-gene receptor
      repertoire from psoriasis skin (different layers) was compared with peripheral
      blood T cells by employing RNA polymerase chain reaction (PCR) amplification. T
      cell receptor (TCR) BV 5.1, 11, 12, 13.1 and 16 were utilized to a significantly
      higher degree in areas close to the basal layers when compared to CD4+, CD8+ or
      unfractionated blood T cells from the same patients, whereas only BV11 and 13.1
      genes of T cells from deeper layers of the dermis showed such a skewed usage. No
      biased usage of TCRBV genes was observed in superficial layers or in whole skin.
      Furthermore, T cell receptor junctional diversity analysed by high resolution gel
      electrophoresis showed skin psoriatic T cells to be poly- or oligoclonal. In
      conclusion, we show that TCRBV gene usage from different layers of psoriatic skin
      has a different pattern compared with the corresponding gene usage in circulating
      peripheral blood T cells. This pattern may implicate possible skin-associated
      antigen or superantigens activating a limited number of T cells in areas of skin
      close to basal layers, which in turn could promote keratinocyte proliferation.

PMID- 9160100
TI  - Analysis of the T-cell receptor V beta usage in monozygotic and dizygotic twins
      living in a Plasmodium falciparum endemic area in west Africa.
AB  - To investigate the influence of genetic and/or environmental factors in the
      development and shaping of the human peripheral T cell repertoire the authors
      studied the T-cell receptor (TCR) V beta usage in 10 adult monozygous (Mz) and
      nine dizygous (Dz) twin pairs living in a Plasmodium falciparum endemic area in
      West Africa. The TCR repertoire was determined using a small panel of anti-V beta
      specific monoclonal antibodies (MoAbs) using conventional immunofluorescence
      assays. The results revealed that the V beta repertoire was similar to that
      recently described for a Caucasian population using a similar panel of
      antibodies. The frequencies of particular V beta genes tested were influenced
      neither by anti-malarial antibody titres nor by parasite densities, indicating
      that the P. falciparum parasite is not a dominating factor in determining the
      peripheral T cell repertoire. All donors were human leucocyte antigen (HLA) class
      I and II typed; no association was found between the expression of any V beta
      genes and MHC haplotype. The V beta usage was more concordant within the Mz than
      within the Dz pairs. For a group comprising four HLA class II identical
      individuals, the average within-pair difference was significantly greater than
      for the whole Mz group, but similar to that seen for the total Dz group. Thus,
      the data suggest that genetic, rather than environmental, factors have a profound
      effect on the shaping of the human circulating T cell repertoire and that the
      major genetic factors are encoded by non-HLA class II genes.

PMID- 9160101
TI  - Inhibition of LPS and Plasmodium falciparum induced cytokine secretion by
      pentoxifylline and two analogues.
AB  - Pentoxifylline and the two analogues HWA138 and HWA448, at concentrations
      exceeding 60 micrograms/ml, inhibited malaria antigen or lipopolysaccharide (LPS)
      induced TNF-alpha and IL-1 alpha secretion, but not IL-6 secretion, from human
      peripheral blood mononuclear cells in vitro. HWA448 had lower inhibitory activity
      in vitro than pentoxifylline and HWA138. A small enhancement of cytokine
      secretion was induced by pentoxifylline and the two analogues at low
      concentrations. The drugs did not affect cell viability. Pentoxifylline, HWA138
      and HWA448 also inhibited LPS induced TNF production in vivo in female CF1xBalb/c
      mice. The drugs were inhibitory at 0.5-1 mg per mouse when mixed with LPS, and 1
      mg per mouse of the drugs was inhibitory when injected 1 h before LPS challenge.
      HWA448 had similar inhibitory activities in vivo compared to pentoxifylline and
      HWA138, possibly because of the longer serum half-life of HWA448. The
      pentoxifylline analogues may have lower toxicity than pentoxifylline itself and
      may therefore be useful in future treatment of diseases induced by endotoxic
      substances.

PMID- 9160102
TI  - The amino acid sequence of the glycosylated amyloid immunoglobulin light chain
      protein AL MS.
AB  - The authors report on the amino acid sequence of the glycosylated amyloid protein
      AL MS. The amyloid fibrils were extracted from the spleen of a patient (MS.) with
      amyloidosis. The protein AL MS was purified from the amyloid fibrils by gel
      filtration. SDS-PAGE performed on the purified protein material showed
      glycosylated protein bands in the range of 22 to 32 kDa, corresponding to
      polymerization of N-terminal fragments. The protein was characterized by amino
      acid analysis and Edman degradation. Tryptic digest combined with Staphylococcal
      V8 protease, chymotrypsin and pyroglutamate aminopeptidase digestion, as well as
      cleavage with BNPS-skatole, established the complete amino acid sequence of 168
      residues. The protein was compared to other proteins in the SWISSPROT databank,
      showing homology with the immunoglobulin light chain variable subgroup lamda I.
      AL MS showed some unique amino acid substitutions. Highly conserved residues
      Gly(57) and Arg(61), were exchanged to arginine and glutamine, respectively,
      possibly altering the three- dimensional structure of the protein.

PMID- 9160103
TI  - In vitro interference with hepatocellular uptake of bile acids by xylene.
AB  - Occupational exposure to a mixture of two widely used aromatic hydrocarbon
      solvents, xylene and toluene, has been associated with a significant rise in the
      concentrations of serum bile acids (SBA). We have recently shown that toluene
      interferes with the transport of bile acids by hepatocytes and this could explain
      elevated SBA after occupational exposure or following in vivo administration of
      this compound to experimental animals. However, it is not known if xylene, like
      its monomethylated homologue, toluene, could interfere with the processes of bile
      acid transport by hepatocytes. Therefore, the present studies were undertaken to
      examine this possibility. Direct addition of a non-cytotoxic dose (2.5
      microliters/2.8 x 10(6) cells) of xylene (in vapour phase) to hepatocytes
      isolated from untreated rats significantly inhibited the initial rates
      (determined from slope of the lines in the linear range (20-80 s)) of uptake (V0)
      of 10 microM cholic acid (CA) and-taurocholic acid (TC) by 37 and 48%,
      respectively (P < 0.05). Similarly, accumulation of these substrates by
      hepatocytes over an extended incubation time up to 30 min was significantly
      inhibited to the same extent by xylene exposure. This inhibitory effect was found
      to be reversible when sufficient time was allowed for the cells to recover. In
      contrast, the initial rates (V0) of efflux (determined from slope of the lines in
      the linear range (1-5 min)) of these bile acids (25 microM) and their continuous
      efflux (up to 30 min) from preloaded cells incubated with a similar dose of
      xylene were not (except for the 1 min time point) significantly different from
      those of controls. In conclusion, xylene interferes with the transport of bile
      acids by hepatocytes in a manner largely similar to that of its monomethylated
      homologue, toluene. These findings extend our previous observations on aliphatic
      and aromatic hydrocarbon solvents and provide mechanistic data at a cellular
      level to support a causal role for xylene (as well as toluene) in raised SBA
      levels of exposed individuals.

PMID- 9160104
TI  - Renal transepithelial secretion of ochratoxin A in the non-filtering toad kidney.
AB  - Renal excretion is an important way of elimination for the nephrotoxin ochratoxin
      A (OTA). Because binding to proteins hinders filtration, excretion is mainly due
      to proximal tubular secretion. The goal of this study was to investigate the
      kinetics of secretion as well as the extent of urine and tissue accumulation in
      situ using the non-filtering amphibian kidney model. Transepithelial secretion is
      a saturable process (K(m) = 0.63.10(-6) mol/l) and leads to a concentration
      dependent accumulation of OTA in the tubular lumen and in renal tissue. Maximum
      accumulation achieved is approximately 14-fold as compared to the perfusate
      concentration. There was no accumulation in the tubular lumen as compared to
      renal tissue (lumen-to-tissue concentration ratio approximately 1). Tissue and
      tubular lumen accumulation were reduced to approximately 40% of control in the
      presence of 10(-3) mol/l p-aminohippurate (PAH). Addition of 10(-3) mol/l alpha
      ketoglutarate (KG) to PAH-containing perfusate did not lead to a further
      reduction of secretion. By contrast, addition of 10(-2) mol/l L-phenylalanine (L
      Phe) reduced secretion further to approximately 25% of control. In the presence
      of 10(-3) mol/l probenecid tissue accumulation was reduced to 7% and tubular
      lumen accumulation to 1% of control. Lumen-to-tissue concentration ratio
      decreased to 0.15 in the presence of probenecid, indicating an inhibitory action
      at the luminal membrane. Addition of albumin to the perfusate, reduced secretion
      to only 50% of control, whereas the concentration of free OTA was reduced below
      1% as compared to control. The results of this study show that transepithelial
      secretion is an effective way for accumulation of OTA in the tubular lumen and
      thus its urinary excretion. Transport via the basolateral organic anion and a
      basolateral amino acid carrier are the active steps in transepithelial secretion.
      Luminal exit of OTA is a passive process. Furthermore, tissue accumulation by the
      active transport across the basolateral membrane supports the toxic action of OTA
      on proximal tubular cells. Due to the qualitative similarity of organic anion
      transport our findings should also apply for the mammalian kidney.

PMID- 9160105
TI  - Thymic regression and apoptosis in the rat after treatment with the Leydig cell
      cytotoxin ethylene dimethanesulphonate (EDS).
AB  - Ethylene dimethanesulphonate (EDS) is an alkylating agent which is widely assumed
      to specifically kill Leydig cells leaving other biological systems intact.
      However, after EDS treatment of the male rat the thymus reversibly involutes and
      the gonadal regional lymph nodes are activated. In the present experiments we
      have demonstrated that EDS has a direct action upon the thymus both in vivo and
      in vitro. EDS treatment of the intact and castrated male rat and the intact
      female rat caused regression of the thymus by up to 50% 3 days later. Total
      cellularity decreased while the proliferative index increased suggesting a
      compensatory mechanism. Thymocytes were exposed to EDS in vitro and the response
      compared to the glucocorticoid methylprednisolone (P), a well characterised
      thymic apoptotic stimulant. EDS and P increased apoptosis in the thymocyte as
      characterised by the appearance of cells containing nuclei with apoptotic
      morphology and with DNA fragmentation visualised by a characteristic ladder after
      agarose gel electrophoresis. The effects of both EDS and P were time and dose
      dependent but, in contrast to the effects in Leydig cells, P was the most
      effective apoptotic stimulus (for instance 100%-P compared to 30%-EDS or 7%
      control/DMSO after 24 h incubation). The immunological responses of the gonadal
      lymph nodes were not associated with testicular regression as it was seen in the
      castrated rat but may be related to a direct action upon the epididymis. In
      conclusion, tissue specificity of the Leydig cell cytotoxin needs to be extended
      to the thymus and epididymis. The mode of cell death in Leydig cells and
      thymocytes after both glucocorticoids and EDS is apoptosis which suggests that
      they possess some common mechanism(s) which is responsible for the toxicity of
      these diverse compounds.

PMID- 9160106
TI  - Cytotoxicity of food preservatives in cultured rat hepatocytes loaded with
      linolenic acid.
AB  - We investigated the ability of eight food preservatives to induce lipid
      peroxidation in normal and alpha-linolenic acid (LNA)-loaded cultured rat
      hepatocytes. On the addition of sodium dehydroacetate (DHA-Na), potassium sorbate
      (SA-K) or thiabendazole (TBZ) to the cell culture, lipid peroxidation, assessed
      in terms of the production of malondialdehyde (MDA), was induced in LNA-loaded
      cells, but not in normal cells. At the low concentrations, induction of lipid
      peroxidation in LNA-loaded cells was highest with TBZ, whereas at high
      concentrations DHA-Na greatly induced lipid peroxidation. The occurrence of lipid
      peroxidation in LNA-loaded cells was accompanied by a decrease in cellular GSH
      levels with the three preservatives and by a decrease in cellular protein-SH
      levels with DHA-Na and TBZ. Furthermore, cell injury, measured by the release of
      LDH, was produced in LNA-loaded cells exposed to DHA-Na and SA-K. The addition of
      TBZ caused substantial cell injury in normal cells, and even greater injury in
      LNA-loaded cells. The prevention of lipid peroxidation in LNA-loaded hepatocytes
      by addition of an antioxidant, N,N'-diphenyl-p-phenylenediamine (DPPD) almost
      completely prevented DHA-Na- and SA-K-induced cell injury, and reduced TBZ
      induced cell injury. The addition of diphenyl (DP), o-phenylphenol (OPP) or butyl
      p-hydroxybenzoate (BHB) caused severe cell injury, in association with a marked
      decrease in cellular levels of both of GSH and protein-SH in both groups of
      cells. However, lipid peroxidation was not detectable in either group of cells
      exposed to these preservatives. Sodium propionate (PA-Na) and sodium benzoate (BA
      Na) had little effect on any cytotoxic parameter in either group of cells.

PMID- 9160107
TI  - Loss of the metal binding properties of metallothionein induced by hydrogen
      peroxide and free radicals.
AB  - The relationship between the metal-binding properties of metallothionein (MT) and
      its ability to interact with peroxides and free radicals was explored in vitro.
      The binding of 109Cd to MT and the thiol density of the protein were determined
      after incubation of a purified Zn/Cd-metallothionein preparation with either
      hydrogen peroxide alone, or with a number of free radical generating systems.
      Exposure of MT to H2O2, whether in the presence or absence of Fe2+, resulted in
      the progressive loss of the thiol residues of the protein and led to a parallel
      decrease of its 109Cd-binding capacity. These changes correlated with r values of
      0.999 (P = 0.001) and 0.998 (P = 0.001), in the absence and presence of iron,
      respectively. The effects of H2O2, alone or plus Fe2+, on MT were completely
      prevented by catalase, but totally unaffected by superoxide dismutase or
      desferrioxamine. Exposure of MT to xanthine/xanthine oxidase also led to thiol
      oxidation and to a concomitant loss of the Cd-binding properties. In this system,
      both changes correlated with an r of 0.993 (P = 0.001) and were completely
      inhibited by superoxide dismutase. Exposure of MT to the peroxyl radical
      generator, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH), resulted in the
      progressive loss of its the metal-binding properties and its thiol residues, both
      changes correlating with an r of 0.986 (P = 0.002). The ability of MT to bind
      109Cd, lost as a result of its prior exposure to either H2O2 alone, H2O2 plus
      Fe2+, xanthine/xanthine oxidase, or to AAPH was, in all cases, completely
      recovered after incubation of the modified protein with dithiothreitol. These
      results indicate that H2O2 alone, and/or the oxygen-derived species, superoxide
      anion and peroxyl radicals, can all directly interact in vitro with MT to modify
      the protein oxidatively, and suggest that, under in vivo conditions, these
      species may be implicated as modifying factors of the metal-binding capacity of
      metallothionein.

PMID- 9160108
TI  - Outputs of hepatic copper and cadmium stimulated by tetrathiomolybdate (TTM)
      injection in Long-Evans Cinnamon (LEC) rats pretreated with cadmium, and in
      Fischer rats pretreated with copper and cadmium.
AB  - The Long-Evans Cinnamon (LEC) rat, an inbred mutant rat derived from the Long
      Evans strain, is characterized by spontaneous hepatitis due to gross accumulation
      of hepatic Cu. The accumulation, accompanied by marked induction of
      metallothionein (MT), is believed to be due to the inherent lack of output of Cu
      into the bile duct and blood vessels. In this study, the acute effect of
      tetrathiomolybdate (TTM), a chelator for output of hepatic Cu and Cd in LEC rats
      treated with Cd, was investigated. Female LEC rats were injected subcutaneously
      with Cd (Cd; 1.0 mg/kg) to induce Cd, Cu-MT. Fischer rats were treated with Cd
      (Cd; 1.0 mg/kg) and Cu (Cu; 3.0 mg/kg). Forty-eight hours after the injections of
      metals, TTM (5 mg/kg bw) was injected intravenously under anesthesia. The TTM
      injection rapidly stimulated biliary excretions of Cu (at a microgram/ml level)
      and Cd (at a ng/ml level). Furthermore, Cu and Cd concentrations were increased
      in serum sampled 60 min after the TTM injection. The increase of biliary Cu
      excretion was not accompanied by increased biliary excretion of MT. The TTM
      injection caused the hepatic Cu concentrations to decrease from 306 +/- 2 to 262
      +/- 12 and from 43 +/- 6 to 20 +/- 5 micrograms/g in LEC and Fischer rats,
      respectively. The hepatic Cd concentration was not decreased by TTM treatment.
      Hepatic MT and Cu, but not Cd, concentrations in the MT fraction were also
      reduced by TTM injection. Our results showed that TTM can rapidly remove Cu from
      MT to increase bile and blood Cu levels. The output of Cd stimulated by TTM
      injection may be related to MT reduction resulting from removal of MT-bound Cu.
      Our results indicate that to avoid the toxic effect of Cu, TTM injection is an
      effective initial treatment, although it remains to be established how metals,
      including Cu, are finally metabolized.

PMID- 9160109
TI  - Nephrotoxic effects of bacterial ribonucleases in the isolated perfused rat
      kidney.
AB  - Alterations of the renal function in the isolated perfused rat kidney system
      after application of two bacterial RNases, Bacillus intermedius RNase (binase)
      and ribonuclease produced by Bacillus amyloliquefaciens (barnase), were
      investigated with two different treatment regimens in comparison with
      catalytically inactive derivates of the enzymes, photooxidated at the active site
      His101 binase and inactive mutant His102Gln barnase. For the in vitro approach
      the test enzymes were dissolved in the perfusion media and applied to the kidney
      after removal from the animal. Alternatively, the test ribonucleases were
      administered to rats in vivo and the renal effects were assessed in the isolated
      perfused rat kidney 1 and 6 h after treatment. In the in vitro regimen both
      active enzymes induced time- and concentration-dependent nephrotoxicity reflected
      in enhancement of urinary protein excretion, decline of glucose reabsorption,
      increase of gamma-glutamyltranspeptidase and alkaline phosphatase activities in
      urine. In vivo administration of active binase induced functional impairment of
      the isolated perfused organ in a similar way. None of the inactive RNases in both
      regimens and at all concentrations tested altered any renal parameter. The
      results suggest that RNA degradation may be involved in the nephrotoxic effects
      of bacillar RNases.

PMID- 9160110
TI  - Assessment of the sensitization potential of five metal salts in the murine local
      lymph node assay.
AB  - The murine local lymph node assay (LLNA) has been proposed as a predictive test
      for the identification of sensitizing agents. We used this test to compare the
      sensitization potential of NiSO4, K2Cr2O7, CoCl2, Na2PtCl6 and BeSO4, salts of
      metals which have all been associated with allergic contact dermatitis and either
      bronchial asthma orinterstitial lung disease, by either humoral or cell-mediated
      allergic mechanisms. BALB/c mice (n = 3 per concentration studied, three
      concentrations studied per metal) received three daily applications of the metal
      salt (in DMSO) on the dorsum of both ears. On the fourth day the draining
      auricular lymph nodes were removed and the incorporation of [3H]-thymidine in the
      lymphocytes in culture was compared to that of concurrent vehicle-treated control
      mice, thus enabling to derive a stimulation index (SI), indicative of
      immunological sensitization potential. Each experiment was performed three times.
      Oxazolone and toluene diisocyanate, chosen as positive controls, yielded strongly
      positive SI values (> 20 and > 30 respectively). Na2PtCl6 (SI 2.6 +/- 1.0 at
      2.5%), CoCl2 (SI 2.8 +/- 0.5 at 5%) and possibly also K2Cr2O7 (SI 2.1 +/- 1.2 at
      0.5%) were positive in the LLNA, whereas NiSO4 (SI 0.9 +/- 0.2 at 5%) and BeSO4
      (SI 1.3 +/- 0.6 at 4%) were negative. Although our results are still limited by
      the fact that only one mice strain was tested, they indicate that there is no
      strict relationship between the sensitization potential of metal salts, as
      evaluated in the murine LLNA, and their potential to cause either respiratory or
      dermal allergic disease. Consequently, caution should be exercised before
      proposing the murine LLNA as a valid test to predict the sensitization potential
      of low molecular weight chemicals.

PMID- 9160112
TI  - Mouse mammary tumor virus and the immune system.

PMID- 9160111
TI  - Colorectal cancer and nonsteroidal anti-inflammatory drugs.
AB  - The authors have presented a concise review of the studies which evaluate the
      risk of colorectal cancer among NSAID users. Animals studies have clearly
      documented a protective effect of NSAIDs in preventing colon cancers in a
      carcinogen-induced (AOM) model. NSAIDs are protective in the animal model, even
      if given 14 weeks after administration of the carcinogen, indicating that they
      must be playing a role very early in the adenoma-to-carcinoma sequence of events.
      Several studies have indicated that treatment of FAP patients with NSAIDs causes
      a regression of adenomas that were already present prior to initiation of NSAID
      therapy. Many epidemiological studies have examined the relationship between
      aspirin use and colorectal cancer. Most of these studies have shown a marked
      decrease in the relative risk (40-50%) of colorectal cancer among continuous
      aspirin users. The appropriate dose and duration of aspirin treatment for optimal
      effects are still unknown. Future work, directed at the molecular basis for the
      chemoprotective effects of NSAIDs in humans, may reveal strategies for the
      development of better chemopreventive agents. One effect shared by all NSAIDs is
      their ability to inhibit cyclooxygenase. Presently, it is not clear whether
      inhibition of cyclooxygenase-1 or -2 effects on other signaling pathways are
      required for the protective effect of aspirin and other NSAIDs. The authors and
      others have demonstrated that COX-2 is upregulated from 2- to 50-fold in 85-90%
      of colorectal adenocarcinomas, which makes the COX-2 enzyme a possible target.
      Drugs are currently under development at several pharmaceutical companies that
      preferentially inhibit either COX-2 or COX-2. If COX-2 is found to be a relevant
      target in the prevention of colorectal cancer, then these newly developed, more
      selective NSAIDs may play a role in future chemoprevention strategies.

PMID- 9160113
TI  - Sodium channels and therapy of central nervous system diseases.
AB  - Voltage-dependent Na+ channels have long been recognized targets for anti
      arrhythmic and local anesthetic drugs. Since the mid-1980s, Na+ channels have
      become widely accepted as the primary target of anticonvulsants with
      pharmacological profiles similar to phenytoin, carbamazepine, and lamotrigine.
      Results from animal models and a few preliminary clinical trials suggest that
      this class of drugs may also offer significant potential for reducing the
      neuronal damage caused by ischemic stroke, head trauma, and perhaps certain
      neurodegenerative diseases. Studies using site-directed mutations of Na+ channels
      with electrophysiology have provided extensive insight into both the physiology
      and the interaction of drug molecules with ion channels. This review includes an
      introduction to Na+ channel structure, molecular biology, and physiology as they
      relate to pharmacology. A review of several in vitro actions of Na+ channel
      blockers is provided. Neuroprotective actions with a variety of Na+ channel
      blockers in models of central nervous system disease in animals and in vitro
      models are reviewed. Although many voltage-dependent Na+ channel blockers have
      additional pharmacological targets, the hypothesis that anticonvulsant and
      neuroprotective actions results from the blockade of Na+ channels is explored.

PMID- 9160114
TI  - Anti-adhesion therapy.

PMID- 9160115
TI  - Use of azoles for systemic antifungal therapy.

PMID- 9160116
TI  - Pharmacology of neuronal nicotinic acetylcholine receptor subtypes.
AB  - The search for the physiological function of nicotinic receptors on neurons in
      the brain began with their discovery. It was initially assumed that, as in
      ganglia and at the neuromuscular junction, nicotinic receptors would gate fast
      synaptic transmission in the brain. The best functional evidence now, however,
      points to a role in modifying the release of other transmitters. This does not
      preclude a postsynaptic role in transmission for nicotinic receptors in the
      brain, but attempts to locate such a synapse have not been successful. If fast
      nicotinic synapses are present in the brain, they are probably low in number and
      may be masked by other more prevalent synapses (such as glutamatergic) so
      identification will not be easy. The extent of diversity of nicotinic receptors
      is substantial. At the molecular level this is reflected in the number of
      different genes that encode receptor subunits and the multiple possible
      combinations of subunits that function in expression systems. From the cellular
      level there is a broad diversity of properties of native receptors in neurons.
      Some useful pharmacological tools allow the limited identification of subunits in
      native receptors. For example, block by alpha-bungarotoxin identifies alpha 7,
      alpha 8, or alpha 9 subunits; activation of a receptor by cytisine indicates an
      alpha 7 or beta 4 subunit; and neuronal bungarotoxin block identifies a beta 2
      subunit. Despite the clues to identity gained by careful use of these agents, we
      have not been able to identify all the components of any native receptor based on
      pharmacological properties assessed from expression studies. When both
      pharmacological and biophysical properties of a receptor are taken into
      consideration, none of the combinations tested in oocytes mimics native receptors
      exactly. The reason for this discrepancy has been debated at length; it is
      possible that oocytes do not faithfully manufacture neuronal nicotinic receptors.
      For example, they may not correctly modify the protein after translation or they
      may allow a combination of subunits that do not occur in vivo. Another
      possibility is that correct combinations of subunits have not yet been tested in
      oocytes. Data from immunoprecipitation experiments suggest that many receptors
      contain three or more different subunits. Results from further experiments
      injecting combinations of three or more subunits into oocytes may be
      enlightening. The diversity of receptors may allow targeting of subtypes to
      specific locations. Nicotinic receptors are located presynaptically,
      preterminally, and on the cell soma. The function of the nicotinic receptors
      located on innervating axons is presumably to modify the release of other
      neurotransmitters. It is an attractive hypothesis that nicotinic receptors might
      be involved in modifying the weight of central synapses; however, in none of the
      regions where this phenomenon has been described is there any evidence for
      axoaxonal contacts. The presynaptic receptors described so far are
      pharmacologically unique; therefore, if there are different subtypes of nicotinic
      receptors modifying the release of different transmitters, they may provide a
      means of exogenously modifying the release of a particular transmitter with
      drugs. There are still many basic unanswered questions about nicotinic receptors
      in the brain. What are the compositions of native nicotinic receptors? What is
      their purpose on neurons? Although there is clearly a role presynaptically, what
      is the function of those located on the soma? Neuronal nicotinic receptors are
      highly permeable to calcium, unlike muscle nicotinic receptors, and this may have
      important implications for roles in synaptic plasticity and development. Finally,
      why is there such diversity? (ABSTRACT TRANCATED)

PMID- 9160118
TI  - Pharmacologic approaches to reperfusion injury.

PMID- 9160117
TI  - Structure and function of leukocyte chemoattractant receptors.

PMID- 9160119
TI  - Restenosis: is there a pharmacologic fix in the pipeline?
AB  - One of the most frustrating aspects of restenosis is that it is the result of
      advances in medical care (there was no restenosis before the days of balloon
      angioplasty), yet it seems to be resistant to all that science has to offer.
      Still we believe there is reason to be optimistic. We are at last beginning to
      see some promise from clinical trials, and data being generated confirm some of
      the hypotheses previously generated from animal experiments. Thus the effects
      seen with the GP IIb/IIIa antibody 7E3 suggest that thrombosis may be as
      important in its long-term sequelae as it is for acute reocclusion. The jury is
      still out on whether antiproliferative approaches will be a therapeutic option,
      but local delivery paradigms using novel formulations delivered by catheter or
      impregnated in stents may allow the concept to be tested without the risk of
      systemic toxicity. Plans are also underway for gene therapy trials, although we
      may have to wait for better vector technology before taking these into the
      coronary bed. Perhaps we should move away from the "single pill" approach and
      accept that, like many infections, malignancies, or even heart failure, a
      multifaceted approach with combination therapy will provide the first glimmer of
      that brighter tomorrow.

PMID- 9160120
TI  - Role of adenosine as a modulator of synaptic activity in the central nervous
      system.

PMID- 9160121
TI  - Combination vaccines.

PMID- 9160122
TI  - Pharmacology of potassium channels.

PMID- 9160123
TI  - Migration of silicone through the fibrous capsules of mammary prostheses.
AB  - The usual reaction of the human body to implantation of a silicone prosthesis is
      formation of a fibrous capsule. Local reactions to silicone outside this fibrous
      capsule and distant migration of silicone particles have been described. So far,
      transcapsular migration of silicone particles from the mammary implant through
      the fibrous capsule of mammary prostheses has not been studied. In this
      prospective study 71 capsules found in 40 patients were histologically studied.
      The chi-squared test was applied to evaluate a possible correlation between
      silicone migration on the one hand and implant age and integrity of the
      prostheses on the other. The degree of silicone migration was discerned in four
      stages. Stage 1 represents no silicone particles in the capsule, stage 2
      represents migration up to less than half of the capsule thickness, stage 3 shows
      migration confined to the outer half of the capsule thickness, and stage 4 means
      transcapsular silicone migration. In only 4 of 71 capsules no migration into or
      through the capsule was observed. The degree of silicone migration was
      significantly less in patients in whom the capsule was calcified and was
      significantly more in patients in whom implantation exceeded 12 years. There was
      no significant correlation between the status of the prosthesis (intact,
      bleeding, or ruptured) and the degree of silicone migration.

PMID- 9160124
TI  - Endoscopic retrieval of severed flexor tendons: a study of technique using
      cadaveric hands.
AB  - Retrieval of retracted zone 1, 2, and 3 flexor tendons without a proximal
      incision can occasionally lead to excessive tendon trauma or injury to
      neurovascular structures. To determine if endoscopic flexor tendon retrieval is a
      reliable, reproducible technique, 34 zone 2 flexor tendon lacerations were
      created in four cadaveric hands (2 male; 2 female). The tendons were retracted
      proximally an average of 4.3 +/- 1.9 cm (range, 2-10 cm) through a separate
      transverse wrist incision. A 2.5-mm flexible endoscope was introduced into the
      distal tendon sheath, and all transected tendons (N = 34) were clearly
      visualized. Thirty-two tendons (94%) were retrieved endoscopically by using
      either a loop snare or grasping forceps. Two tendons (6%) in a small female hand
      could not be retrieved endoscopically. This minimally invasive technique may be
      an alternative to the blind grasping maneuvers, proximal incision extensions, and
      counter-incisions in the palm.

PMID- 9160125
TI  - Use of Mitek suture anchors in head and neck reconstruction.
AB  - Attachment of soft tissue to bone is a common problem encountered in head and
      neck reconstruction. Soft-tissue attachment is encountered in the formation of
      slings to recreate oral competence. We report the use of the Mitek suture anchor
      in 7 head and neck reconstruction patients (5 underwent an attachment of a tensor
      fascia lata sling for oral competence and 2 underwent an attachment of a gracilis
      musculocutaneous free flap to recreate facial symmetry). Use of the Mitek anchor
      facilitates soft-tissue-to-bone attachment. Minimal dissection is required and
      secure bony fixation is obtained.

PMID- 9160126
TI  - Treatment of frontal sinus osteoma using a craniofacial approach.
AB  - Osteoma is one of most common benign tumors of the nose and paranasal sinuses,
      with the frontal sinus being its most frequent location. It may be locally
      destructive and aggressive with possible intracranial complications. Osteoma of
      the frontal sinus comprises 57% of all osteomas in the paranasal sinuses. In
      1939, Childrey reviewed 3,510 consecutive sinus radiographs taken for any reason
      and found an incidence of 0.43% of paranasal sinus osteomas. There are many
      operative approaches for frontal sinus osteomas, such as external frontoethmoidal
      approach and osteoplastic frontal sinusectomy, both with high recurrence rates.
      Those traditional operative methods cannot radically eradiate the osteoma grown
      in the posterior table of the frontal sinus. From July 1991 to June 1992, three
      patients with symptomatic frontal sinus osteomas were operated by a craniofacial
      approach. One patient is presented here in detail. A coronal incision is used and
      is found to be beneficial both in surgical exposure and in reconstruction with a
      calvarial bone graft. The patient has been followed for 3.5 years without osteoma
      recurrence.

PMID- 9160127
TI  - Leg morbidity and function following fibular free flap harvest.
AB  - Over a period of 3 years, 50 consecutive free fibular flaps for mandibular
      reconstruction were performed on 47 patients. In 38 patients (81%) a skin paddle
      was included with the flap to provide either mucosal lining or skin cover; in 9
      patients (19%) bone alone was used. Thirty-one patients (66%) required a skin
      graft to close the donor defect in the leg. Donor leg morbidity and function were
      determined by patient questionnaire and by physical examination. Forty-one donor
      sites in 40 patients were available for long-term follow-up. The follow-up ranged
      from 4 to 39 months with an average of 17 months. Immediate postoperative
      infection occurred in the donor site of 1 patient (2%) and required additional
      surgery. There was no other immediate donor site complications when closure
      required skin grafting. Eleven patients (27%) had late donor site morbidity,
      consisting of motor weakness of the great toe in 5 patients, ankle instability
      and/or stiffness in 3 patients, donor site pain in 1 patient, and edema in 2
      patients. All complications were graded as mild in severity by the patient and by
      the examiner. In this series, although most donor site defects required skin
      grafting, short- and long-term morbidity was minimal. After a short
      rehabilitation period, all patients were fully able to engage in all daily and
      recreational activities.

PMID- 9160128
TI  - Age-related outcomes of sleep apnea surgery in infants and children.
AB  - This study was designed to determine whether age at the time of surgery is an
      important influencing factor on outcomes following surgical correction of severe
      refractory obstructive sleep apnea (OSA) in infants and children. Data were
      collected prospectively on 55 children, all with severe OSA refractory to
      conservative medical and surgical measures, who underwent combinations of soft
      tissue and skeletal procedures aimed at relieving their airway obstruction. The
      study population was subdivided for analysis into three groups based on age at
      the time of surgery (> 36 months, > 12 to < 36 months, and < or = 12 months).
      Each child was assessed for clinical outcomes, polysomnography results, and
      complications. Children in the > 36 months group demonstrated a significant
      improvement in respiratory disturbance index (RDI), apnea index, and lowest
      overnight oxygen saturation postoperatively. Only RDI improved significantly in
      the > 12 to < 36 months group. Although there was a trend toward improvement in
      the respiratory indices for the children < or = 12 months of age, they had a
      significantly longer intensive care and hospital stay, a greater mean number of
      extubation attempts, and the highest surgical failure rate (29%). Other
      complications such as infection, atelectasis, or temporary postoperative
      nasopharyngeal tube dependence occurred most frequently in the > 36 months group.
      Surgical management of severe refractory OSA in children age < or = 12 months is
      more difficult and less likely to succeed. The reasons for this are discussed and
      recommendations for management are given.

PMID- 9160129
TI  - A controlled, randomized, double-blind study of ketorolac for postoperative
      analgesia after plastic surgery.
AB  - The present study was designed to evaluate the efficacy and safety of ketorolac
      compared with metamizol (Nolotil) in the control of pain after plastic surgery.
      Almost no literature exists on postoperative pain control in this specialty. A
      multiple-dose, randomized, double-blind study of parallel design was carried out.
      One hundred patients received either ketorolac 30 mg intramuscularly (IM) every 8
      hours or metamizol 2 g IM every 8 hours for postoperative analgesia during the
      first 48 postoperative hours. Pain severity was assessed using a visual analog
      scale. Adverse events were recorded. There were no significant differences
      between the groups in terms of pain scores or frequency of adverse events
      throughout the study. Two postoperative hemorrhages were recorded in the
      ketorolac group. Ketorolac and metamizol were found to be equally safe and
      effective in reducing postoperative pain after plastic surgery. It should be
      noted that 52% of patients in the ketorolac group and 48% in the metamizol group
      considered their postoperative analgesia to be very good. Nevertheless, for
      surgical procedures or for patients in whom postoperative hematoma formation is a
      particular concern, ketorolac probably should not be used.

PMID- 9160130
TI  - Validation of cutaneous pressure threshold measurements for the evaluation of
      hand function.
AB  - The relationship of measures of pressure perception to hand function was
      evaluated by correlating the results of the Mayo Dexterity Test and a timed
      object recognition test with the one- and two-point static and moving touch
      thresholds for the index finger pulp of 44 hands. The Mayo Dexterity Test permits
      the use of vision, while the object recognition test does not. Quantitative
      sensory testing was done with the Pressure-specifying Sensory Device. Cutaneous
      pressure threshold measurements with this device had a statistically significant
      correlation with the small-object subset of the Mayo Dexterity Test (p < 0.006)
      and with the object recognition test (p < 0.001), demonstrating that the Pressure
      specifying Sensory Device is a valid tool for evaluating the sensory aspect of
      hand function.

PMID- 9160131
TI  - Computer-assisted quantitative sensorimotor testing in patients with carpal and
      cubital tunnel syndromes.
AB  - This study reports the use of computer-assisted sensorimotor testing in 75
      patients with chronic peripheral nerve compression. Pinch and grip strength, and
      the cutaneous pressure threshold were measured. The reliability of this equipment
      for repeated measurements was excellent (r = 0.95). The pressure threshold at
      which a one-point static stimulus could be distinguished from a two-point static
      stimulus was found to be the first variable to become abnormal with computer
      assisted sensorimotor testing. Criteria are suggested for screening with this
      equipment to detect carpal and/or cubital tunnel syndrome.

PMID- 9160132
TI  - Ischemic time and free flap success.
AB  - Ischemic time (the time between the interruption and reestablishment of blood
      supply) was reviewed for 700 free flaps used for breast or head and neck
      reconstruction. Flaps that failed had a mean ischemic time of 111.64 minutes,
      while flaps that survived had a mean ischemic time of 91.25 minutes. The
      difference was not statistically significant (p = 0.189). The patients were then
      divided into two groups: those with flap ischemic times of 100 minutes or longer
      and those with flap ischemic times less than 100 minutes. We found that flap
      survival was similar in the two groups. Flap survival was also similar when 75
      minutes and 120 minutes were used to segregate the longer and shorter ischemic
      time groups. When 180 minutes was used to segregate the groups, there was a
      slight trend toward more flap loss in the group with longer ischemic time, but
      the difference was not significant. We conclude that ischemic time is irrelevant
      to flap survival, provided that ischemia is not prolonged past 3 hours or to the
      point where the no-reflow phenomenon occurs.

PMID- 9160133
TI  - Favorable donor site for epidermal cultivation for the treatment of burn scars
      with autologous cultured epithelium.
AB  - It is very important to determine from where we select the donor skin for
      epidermal cultivation in the treatment of burn scar disfigurement. To prove this
      point, we compared the appearance and histology of grafted sites according to the
      different donor sites. Thirty-eight patients with skin color difference and
      irregular contours of matured burn scars were superficially abraded and underwent
      autologous cultured epithelial grafting. These patients were followed more than 2
      years. The donor skin for epidermal cultivations was taken from the buttock
      (group 1, 8 patients), sole (group 2, 6 patients), and adjacent to the site of
      the scar (group 3, 24 patients). In group 3, skin elasticity was also measured
      after 2 years. Hypo- and hyperpigmentation were well treated with autologous
      cultured epithelial grafting. The most favorable results in terms of color match
      were obtained in group 3, where the skin color resembled surrounding normal skin.
      The skin tension returned to almost normal. In group 2, the histology of the
      grafted site resembled the sole epidermis. It was concluded that the general
      principle of conventional skin grafting (i.e., "closer is best") was also correct
      in cultured epithelial grafting. Furthermore, it was revealed that cultured
      epithelium has a site specificity even after grafting.

PMID- 9160134
TI  - Topical administration of prostaglandin E1 with iontophoresis for skin flap
      viability.
AB  - This study was performed to investigate the capability of iontophoretic delivery
      of prostaglandin E1 (PGE1) and the effect of this treatment on the viability of
      skin flaps on the rat dorsum model as described by Hammond and Ronald in 1993.
      The PGE1 level in the tissue sample under the electrode was assessed with
      radioimmunoassay. The iontophoretic treatment (for 20 minutes at 4 mA) with PGE1
      solution (20 micrograms PGE1 in 2 ml saline) showed a significant increase of
      PGE1 in the flap tissue under the negative electrode (p < 0.05). Very little
      increase was observed after the iontophoresis of saline alone. This was not
      statistically significant. Iontophoretic treatment was given for 5 consecutive
      days following flap elevation. The survival area on the seventh postoperative day
      was significantly greater in the PGE1-treated flaps than that of either the
      control or saline-treated flaps. These results confirm the beneficial effect of
      iontophoretic treatment with PGE1 on the augmentation of skin flap viability.

PMID- 9160135
TI  - Successful repair of ectopia cordis using alloplastic materials.
AB  - Ectopia cordis is a very rare congenital anomaly associated with a high mortality
      rate. A successful repair of ectopia cordis with complete absence of sternum was
      achieved in a two-stage procedure. Initial management consisted of coverage of
      skin over the malpositioned heart using bilateral pectoral skin flaps. A second
      more definitive repair was undertaken at age 14 months. Four methyl methacrylate
      struts were used to reconstruct the anterior chest wall and were then covered
      with bilateral pectoralis major muscle flaps. At the 2.5-year follow-up there is
      no evidence of cardiopulmonary compromise and the development of the thorax
      appears normal. We advise that use of alloplastic materials is a valid option in
      managing this difficult congenital anomaly.

PMID- 9160136
TI  - Post-transferred tissue expansion of a musculocutaneous free flap for debulking
      and further reconstruction.
AB  - A free flap used for face and neck reconstruction usually results in tissue
      bulking and needs several debulking procedures to match the contour of the face
      and neck. In this paper we report an experience with a patient who underwent
      tissue expansion of a transplanted musculocutaneous free flap in the face for
      debulking of the flap and four further aesthetic reconstructions of the face and
      neck. The result shows that a transplanted free flap tolerates tissue expansion
      well. The versatile use of tissue expansion shows obvious advantages in that the
      transplanted flap is not only enlarged substantially by means of tissue
      expansion, but it is also debulked at the same time of achieve a desired thin
      flap for further reconstruction of the face and neck.

PMID- 9160137
TI  - Aneurysm of the radial artery following blunt trauma to the wrist.
AB  - Aneurysms involving the distal radial artery are rare lesions which are usually
      secondary to penetrating trauma or iatrogenic injury. Blunt trauma is an
      extremely uncommon cause. In the absence of a history of penetrating vascular
      injury, a radial artery aneurysm may easily be misdiagnosed as a nonvascular mass
      such as a synovial cyst. A diagnostic approach to these lesions is discussed
      emphasizing the role of noninvasive studies in uncomplicated cases. Excision of
      the aneurysm is recommended. The decision to ligate or reconstruct the radial
      artery remains controversial.

PMID- 9160138
TI  - Nonmicrosurgical use of an osteocutaneous parascapular flap for reconstruction of
      a complex hand defect.
AB  - We describe the nonmicrosurgical use of an osteocutaneous parascapular flap as a
      new application in reconstructive hand surgery for reconstruction of a complex
      hand defect resulting from a gunshot injury. This technique, namely the
      transaxillary parascapular flap, is easy to perform and does not require the
      sophisticated equipment and expertise of microsurgery. This is an important
      advantage, especially for developing countries in which microsurgical facilities
      are limited.

PMID- 9160139
TI  - Multiple neurilemomas of the ulnar nerve: a case report.
AB  - Multiple neurilemomas in a patient involving the same peripheral nerve is quite
      rare. We report a case of multiple neurilemomas involving the ulnar nerve.

PMID- 9160140
TI  - Anatomic design of a sensate plantar flap.
AB  - To date, full-thickness skin ulcers of the heel of the foot are still difficult
      wounds to cover. Many choices of coverage are available, but few provide long
      term coverage due to bone exposure, deficient sensibility, and subsequent
      breakdown. An advancement flap based on the medial plantar artery with sensory
      nerve branches is presented with long-term follow-up. This flap is available and
      expendable, with an excellent are of rotation. Reliable circulation and
      sensibility are the key factors for successful reconstruction.

PMID- 9160141
TI  - An inexpensive method of intraoperative skin stretching for closure of large
      cutaneous wounds.
AB  - A simple and inexpensive method for closure of large wounds is presented. A rib
      approximator and two spinal needles, which are readily available in most
      operating rooms, have been utilized to close large cutaneous wounds of the chest
      and thigh after flap harvest.

PMID- 9160142
TI  - A new malleable self-retaining retractor.
AB  - Simple function, wide view, and safety are three important properties of a good
      retractor. Since conventional retractors are not specifically designated for
      extraocular or neurovascular operations, particularly on the head and neck, we
      hereby introduce our self-retaining retractor. This instrument is composed of an
      ordinary self-retaining retractor and a pair of malleable retractors. This
      retractor has the previously mentioned properties of a good retractor. We have
      used this type of retractor for a variety of plastic surgical operations.

PMID- 9160143
TI  - Re: Effectiveness of silicone sheets in the prevention of hypertrophic breast
      scars.

PMID- 9160144
TI  - Re: UltraPulse carbon dioxide laser with computer pattern generator for facial
      cosmetic surgery and resurfacing.

PMID- 9160145
TI  - Re: The latissimus dorsi perforator-based fasciocutaneous flap.

PMID- 9160147
TI  - Defect of the columella with loss of septum and soft palate: a case report.

PMID- 9160146
TI  - Prognostic importance of tumor diameter in nodular melanomas.

PMID- 9160148
TI  - Selected list of books and journals for the small medical library.
AB  - The introduction to this revised list (seventeenth version) of 610 books and 141
      journals addresses the origin, three decades ago, of the "Selected List of Books
      and Journals for the Small Medical Library," and the accomplishments of the late
      Alfred N. Brandon in helping health sciences librarians, and especially hospital
      librarians, to envision what collection development and a library collection are
      all about. This list is intended as a selection guide for the small or medium
      size library in a hospital or similar facility. More realistically, it can
      function as a core collection for a library consortium. Books and journals are
      categorized by subject; the book list is followed by an author/editor index, and
      the subject list of journals by an alphabetical title listing. Due to continuing
      requests from librarians, a "minimal core" book collection consisting of 78
      titles has been pulled out from the 200 asterisked (*) initial-purchase books and
      marked with daggers ([symbol: see text]). To purchase the entire collection of
      books and to pay for 1997 journal subscriptions would require $101,700. The cost
      of only the asterisked items, books and journals, totals $43,100. The "minimal
      core" book collection costs $12,600.

PMID- 9160150
TI  - Health information-seeking behavior and older African American women.
AB  - This study explored the ways in which urban, older, African American women obtain
      health information and some of the factors that influence such activity. Among
      the possible determinants examined were self-perceived literacy, access to health
      information, and mobility. The findings suggest that respondents receive health
      information from their physicians, the mass media, and members of their social
      networks. The results of this research also indicated that members of this
      population have a highly positive perception of the public library, although only
      a small segment use the library regularly, and that it may be in the interest of
      the library to investigate the role it could play in providing health information
      to older adults.

PMID- 9160149
TI  - Improving access to knowledge-based health sciences information: early results
      from a statewide collaborative effort.
AB  - Access to biomedical literature has been shown to reduce the patient's length of
      stay and thus reduce the cost of the hospital visit. Unfortunately, access to the
      most current information, at the time and place of need, requires a substantial
      commitment of resources in the form of staff expertise, computer hardware and
      software, and user training. The cost of these resources may be prohibitively
      high for all but the largest institutions. The Arizona Health Information Network
      (AZHIN) brings together librarians, information systems specialists, and health
      care professionals from hospitals throughout the state in an effort to share
      resources and expertise. By reducing the cost of access, AZHIN has increased the
      availability of health-related information across the state. Progress in AZHIN's
      first two years is described.

PMID- 9160152
TI  - Analyzing the research record of an institution's list of faculty publications.
AB  - Few health sciences libraries maintain databases and produce bibliographies of
      the publications of their institution's faculty. By offering such services,
      libraries can provide faculty members with a qualitative analysis of where and
      how their research is cited and its impact in the fields of biomedicine and
      related health sciences. Journal Citation Reports (JCR), produced by the
      Institute for Scientific Information, is a powerful tool that provides
      information on citations appearing in the largest, most frequently used, most
      cited, and highest-impact journals. This paper discusses the role libraries play
      in providing information about faculty publications, reviews how JCR is used by
      libraries, discusses how the Ehrman Medical Library of the New York University
      Medical Center uses JCR, and makes recommendations for the use of JCR to
      strengthen the librarian's role in providing information to faculty about the
      value of their research.

PMID- 9160151
TI  - BIOETHICSLINE use by medical students: curriculum-integrated instruction and
      collection development implications.
AB  - BIOETHICSLINE uselogs were analyzed during months when second-year medical
      students were engaged in ethics coursework that included curriculum-integrated
      bibliographic instruction. Uselog data showed that peak activity occurred while
      students were preparing a required paper. Further uselog analysis indicated that
      students applied database features such as controlled vocabulary, the "explode"
      command, and a combination of multiple search concepts. In addition, the study
      examined journal use and interlibrary loan activity for a correlation with online
      search activity. Higher bioethics journal use and interlibrary loan statistics
      coincided with peak BIOETHICSLINE activity periods. Citation analysis of student
      bibliographies reflected the interdisciplinary nature of BIOETHICSLINE and the
      need for ethics, legal, and clinical information sources in a bioethics
      collection. This study suggests that the integration of bibliographic instruction
      and the coordination of collection development with students' curricular needs
      lead to increased and more competent use of information resources.

PMID- 9160153
TI  - Hospital-based patient information services: a model for collaboration.
AB  - Crouse Hospital in Syracuse, New York, is a 612-bed, not-for-profit teaching
      hospital with 2,500 employees. A close examination of operations at Crouse
      facilitated the development of a patient education task force that used a
      comprehensive, multidisciplinary approach to meet the educational needs of both
      patients and clinicians. The collaborative process involved all hospital
      departments. Within eighteen months, patient requests for information rose from
      3% to 30% of total requests made at the hospital. Requests were made directly to
      the library or through a member of the health care team. Hospital staff members
      were surveyed about information needs and availability, and a library work plan
      was devised, setting standards of service for a multimedia approach. Work
      redesign improved the library staff's ability to integrate patient education into
      daily operations. Cost savings were achieved through the elimination of
      duplicated resources and services throughout the hospital. The management model
      developed at Crouse was the result of a needs assessment and a multidisciplinary,
      collaborative process. The model emphasizes communication links among disciplines
      rather than physical locations. The Crouse experience validates the development
      of hospital-based consumer health information services.

PMID- 9160154
TI  - Assessing and addressing the library needs of health care personnel in a large
      regional hospital.
AB  - A needs assessment survey was conducted by the Medical Library staff of St.
      John's Health System, Inc., in Springfield, Missouri, to document the library
      needs of non-physician health care personnel. The intended use of the survey was
      threefold: first, to collect baseline data from non-physician health care
      employees; second, to gather recommendations from both library users and non
      users to be included in library planning and improvements; and third, to promote
      the library during the survey process. Study results, along with an
      implementation report detailing actions taken to enhance strengths and address
      weaknesses identified in the needs assessment survey, are presented.
      Opportunities for further investigation of library needs are also reported.

PMID- 9160155
TI  - A library for the twenty-first century: the Galter Health Sciences Library's
      renovation and expansion project.
AB  - A renovation and expansion project at the Galter Health Sciences Library of
      Northwestern University strikes a balance between traditional and future
      libraries, library ambiance and high technology, old and new. When guided by a
      vision of future building use, renovation projects can succeed in meeting many
      institutional goals as a viable alternative to new library buildings. Issues
      addressed include planning considerations, architectural history, library design,
      building features, information technology considerations, and ideal library space
      design when new construction is not possible.

PMID- 9160157
TI  - The ADONIS experience: CD-ROM full-text access to the journal literature in an
      academic health sciences library.

PMID- 9160156
TI  - Characteristics of information resources preferred by primary care physicians.
AB  - Primary care physicians use patient data, medical knowledge, logistic
      information, and population statistics. They rely on their personal knowledge to
      care for their patients, their top priority. When they seek information beyond
      this personal knowledge base, they frequently want information in the context of
      the care of a specific patient. They also continually add to their personal
      knowledge base. Less frequently, they seek logistic information and population
      statistics. For patient-specific questions, physicians most often seek medical
      facts or medical opinions. A physician may be persistent in seeking information
      if the patient's problem is perceived to be urgent and the doctor believes a
      definitive answer exists. Information resources for answering clinical questions
      should be readily available, familiar, and quick to use. Lifelong learning
      activities should also be readily available, and they should require a minimum of
      time, effort, and expense. Minimal cost in time and effort is particularly
      important when knowledge is sought as a part of ongoing medical learning, since
      there is less immediate benefit to balance the time and effort invested in
      information seeking.

PMID- 9160158
TI  - Internet skills: an analysis of position advertisements 1991-1995.

PMID- 9160159
TI  - Electronic "library without walls" in a hospital library.

PMID- 9160160
TI  - A new vessel: the dedication of the Galter Health Sciences Library.

PMID- 9160161
TI  - Preserving the magic and providing comfortable digital chairs.

PMID- 9160162
TI  - The effects of temperature upon calcium exchange in intact cultured cardiac
      myocytes.
AB  - Cardiac myocyte Ca transport systems, such as sarcoplasmic reticulum Ca-ATPase
      and sarcolemmal Na/Ca exchange (Na/Ca), are critically dependent on temperature.
      The purpose of this work was to study the effect of temperature on cellular Ca
      compartmentation and its exchange characteristics in intact functional neonatal
      cultured myocytes. The Na/Ca mediated Ca exchange (CaNa/Ca)--including its
      sarcoplasmic reticulum (SR) and sarcolemmal (SL) contributions, a slow exchange
      component related to mitochondrial Ca and the La displaceable Ca pool were
      studied combining isotopic and gas-dissection techniques for membrane isolation.
      The major findings of this study are: (i) The amount of Ca exchanged through
      CaNa/Ca is clearly dependent on temperature (Q10 approximately 1.6) in the range
      studied (17-37 degrees C); (ii) the addition of 1 microM nifedipine does not
      modify the temperature dependence of CaNa/Ca; (iii) the sarcolemmal bound
      fraction contributing to CaNa/Ca is not changed by temperature; (iv) the increase
      in CaNa/Ca with temperature is explained by an increment in the contribution of
      SR-Ca to CaNa/Ca; (v) a fraction of SR which does not exchange via CaNa/Ca at low
      temperatures can be released and mobilized by caffeine-this caffeine sensitive
      fraction is reduced as temperature is increased and is no longer measurable as a
      separate entity at 37 degrees C; (vi) if we consider (iv) and (v) together, SR
      content would be temperature dependent with a Q10 of approximately 1.5; (vii) a
      La displaceable pool, which represents over 66% of the total exchangeable Ca,
      increases in the range of 22-33 degrees C with a Q10 of 1.25 which is consistent
      with a pool distribution of 70% SL-bound and 30% SR-derived [Post J.A., Langer
      G.A. Cellular origin of the rapidly exchangeable calcium pool in the cultured
      neonatal rat heart cell. Cell Calcium 1992; 13: 627-634]; and (viii) the rate
      constant for the mitochondrial Ca component increases by 60% from 22 degrees C to
      37 degrees C, but Ca content in this organelle is not modified over this
      temperature range.

PMID- 9160163
TI  - Nucleoplasmic and cytoplasmic differences in the fluorescence properties of the
      calcium indicator Fluo-3.
AB  - The fluorescent indicator Fluo-3 is widely used to monitor the calcium
      concentration ([Ca2+]) in the cytoplasm and nucleus of various cells. Estimates
      of nuclear [Ca2+] are based on the assumption of identical behavior of Fluo-3 in
      different cellular compartments. The assumption is not valid if the fluorescence
      properties of the dye are altered by the nuclear environment, independent of the
      [Ca2+]. To determine the effects of the nucleoplasm on the behavior of Fluo-3, we
      applied laser scanning confocal microscopy and spectrophotometry to measure
      fluorescence intensity as well as emission and absorbance spectra of the Ca2+
      indicator, Fluo-3. Spectra were measured in intact Xenopus oocytes, neuroblastoma
      cells, and cytoplasmic and nucleoplasmic homogenates. The fluorescence signal in
      intact cells loaded with Fluo-3 was approximately 2-times higher in the nucleus
      when compared to the cytoplasm. The fluorescence intensity of Fluo-3 in
      nucleoplasmic homogenates was higher than in cytoplasmic homogenates or internal
      buffers even when [Ca2+] was clamped. Despite identical [Ca2+], pH, and
      temperature, the emission and absorbance spectra of Fluo-3 from nuclear
      homogenates displayed a higher fluorescence at each wavelength measured when
      compared to spectra from cytoplasmic homogenates or internal buffer solutions,
      and saturated above 100 nM. These findings demonstrate that the composition of
      the nucleoplasm changes the fluorescence properties of the calcium indicator Fluo
      3. Consequently, analysis of nuclear calcium dynamics must take into account the
      distinct behavior of Fluo-3 in different cellular compartments.

PMID- 9160164
TI  - Gating of the skeletal calcium release channel by ATP is inhibited by protein
      phosphatase 1 but not by Mg2+.
AB  - We have previously found that dephosphorylation/phosphorylation of the calcium
      release channel (CRC) of skeletal muscle confers channel
      sensitivity/insensitivity to the block by physiological [Mg2+] (approximately 1
      mM). These studies have now been extended to modulation by ATP. Terminal
      cisternae vesicles of sarcoplasmic reticulum were incorporated into planar lipid
      bilayers. CRC gating by ATP (0.67 mM), in the absence of Ca2+ (< 1nM), was
      studied by treatment with protein kinase A (PKA) or phosphatase 1 (PPT1) and
      assayed in the presence and absence of free Mg2+ (1 mM). PPT1, PKA, and Mg2+ were
      directly applied to the bilayer using the microsyringe method, which controls the
      environment of the CRC in the bilayer for phosphorylation/ dephosphorylation
      cycles and for assays. PKA treated channels were activated by ATP to high open
      probabilities, while PPT1 treated channels were not activatable by ATP. Opening
      and closing of channels during cycles of PKA and PPT1 applications, respectively,
      provided evidence that the change of CRC activity is due to cyclic
      phosphorylation/dephosphorylation. Free Mg2+ (1 mM) did not block channels
      activated by ATP. The new finding is that channel gating by ATP can be controlled
      by the state of phosphorylation without inhibition by free Mg2+.

PMID- 9160165
TI  - Calcium-activated potassium channels in cultured human endothelial cells are not
      directly modulated by nitric oxide.
AB  - Nitric oxide has been proposed to directly activated large conductance Ca(2+)
      dependent K+ channels (BKCa) [Bolotina V.M., Najibi S., Palacino J.J., Pagano
      P.J., Cohen R.A. Nitric oxide directly activates calcium-dependent potassium
      channels in vascular smooth muscle. Nature 1994; 368: 850-853]. The nitric oxide
      (NO) donor S-nitrosocysteine (SNOC) was used to evaluate a possible direct
      modulation of BKCa by NO in EAhy926 (EA cells), a cultured human umbilical vein
      derived endothelial cell line, using the whole-cell, cell-attached and inside-out
      configuration of the patch-clamp technique, together with simultaneous
      amperometric measurement of NO and the concentration of free intracellular
      calcium [Ca2+]i. BKCa channels with a large conductance of approximately 190 pS,
      voltage-dependent activation and a reversal potential close to -80 mV have been
      identified in EA cells. Exposure of EA cells in the experimental chamber to 1 mM
      SNOC delivered approximately 5 microM NO, as recorded by an amperometric probe in
      situ. SNOC produced a modest increases in [Ca2+]i that was insufficient to
      activate BKCa channels. NO alone neither activated BKCa channels directly nor
      modulated preactivated BKCa channels in EA cells. These results do not support a
      direct modulatory effect of NO on large conductance BKCa channels in cultured
      endothelial cells.

PMID- 9160166
TI  - Binding and activity of the nine possible regioisomers of myo-inositol
      tetrakisphosphate at the inositol 1,4,5-trisphosphate receptor.
AB  - All 9 racemic regioisomers (15 enantiomerically) of myo-inositol
      tetrakisphosphates (IP4s): DL-Ins(1,2,4,5)P4 [A], DL-Ins(1,2,4,6)P4 [B],
      Ins(1,2,3,5)P4 [C], Ins(1,3,4,6)P4 [D], Ins(2,4,5,6)P4 [E], DL-Ins(1,3,4,5)P4
      [F], DL-Ins(1,2,5,6)P4 [G], DL-Ins(1,2,3,4)P4 [H] and DL-Ins(1,4,5,6)P4 [I]
      [Chung S-K., Chang Y-T. Synthesis of all possible regioisomers of myo-inositol
      tetrakisphosphate. J Chem Soc Chem Commun 1995; 11-13] were investigated for
      their ability to bind to the D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]
      receptor in bovine adrenal cortical membranes, and for their ability to mobilize
      45Ca2+ from Ins(1,4,5)P3-sensitive Ca2+ stores in permeabilized Chinese hamster
      ovary (CHO) cells. DL-Ins(1,2,4,5)P4 (Ki = 11 nM) bound to Ins(1,4,5)P3 receptors
      with an affinity only 2-fold lower than Ins(1,4,5)P3 (Ki = 6 nM). Ins(1,2,3,5)P4,
      Ins(1,3,4,6)P4, Ins(2,4,5,6)P4, DL-Ins(1,3,4,5)P4, DL-Ins(1,2,3,4)P4 and DL
      Ins(1,4,5,6)P4 bound with affinities of between 0.4-0.7 microM. DL-Ins(1,2,4,6)P4
      and DL-Ins(1,2,5,6)P4 bound to the Ins(1,4,5)P3 receptor with low affinity
      (approximately 2-3 microM). All but one of the IP4s mediated release of 45Ca2+
      from stores of permeabilized CHO cells with a similar rank order of potency as
      that for Ins(1,4,5)P3 receptor binding, being between 16-fold and 50-fold less
      potent at releasing 45Ca2+ compared with their apparent binding affinities to the
      Ins(1,4,5)P3 receptor. The notable exception was Ins(1,2,3,5)P4, which showed an
      approximately 200-fold lower potency compared with its affinity for the
      Ins(1,4,5)P3 receptor. Ins(1,2,3,5)P4 may be a useful lead compound for the
      rational design of novel synthetic Ins(1,4,5)P3 analogues possessing structure
      activity profiles with relatively high binding affinity, but low intrinsic
      efficacy, and hence partial agonists and antagonists at the Ins(1,4,5)P3
      receptor.

PMID- 9160167
TI  - Identification and characterization of inositol 1,4,5-trisphosphate receptors in
      rat testis.
AB  - PCR analysis and immunoblotting with isoform specific antibodies was used to
      identify the presence of type I, II and III inositol 1,4,5-trisphosphate
      receptors (InsP3Rs) in rat testis. PCR analysis also revealed that rat testis
      express both forms of the S1 splice variant (S1+ and S1-), but only the S2- from
      of the S2 splice variant of the type I InsP3 receptor. PCR analysis was also used
      to identify InsP3R isoform expression at a cellular level using myoid, Sertoli
      and germ cells derived from the testis of Wistar rats. The extent of [3H]-InsP3
      binding was found to be 9 times lower for testicular microsomes than for
      cerebellar microsomes, with a Bmax of 1.4 pmoles/mg protein compared to 12.5
      pmoles/mg protein for cerebellar microsomes. The Kd for InsP3 binding to its
      receptor in testicular microsomes was 60 +/- 10 nM which was similar to that
      found for cerebellar microsomes (80 +/- 20 nM). InsP3-induced Ca2+ release (IICR)
      in testicular microsomes was found to have an EC50 (concentration which causes a
      half-maximal response) of 0.5 +/- 0.03 microM, also similar to that seen for
      cerebellar microsomes (0.3 microM). Maximal IICR occurred at about 20 microM
      InsP3, with up to 4% of total intracellular Ca2+ stores being mobilized as
      compared to between 10-30% for cerebellar microsomes. Time resolved IICR using
      stopped-flow spectrofluorimetry, showed the kinetics of IICR for this testis
      preparation to be monophasic with a maximum rate constant of 0.15 s-1 at 30
      microM InsP3. The rate constants are 7 times slower than values for cerebellar
      microsomes under similar conditions (approximately 1 s-1) and taken together with
      the binding data support the proposal that the receptor density/Ca2+ store is
      approximately 8 times lower than seen in cerebellar microsomal vesicles. The
      pharmacological properties as assessed using heparin and InsP3 analogues also
      confirmed similar behaviour for testicular InsP3Rs and cerebellar InsP3Rs.

PMID- 9160168
TI  - Inhibition of mitochondrial calcium efflux by clonazepam in intact single rat
      cardiomyocytes and effects on NADH production.
AB  - The aims of this study were to determine: (i) whether clonazepam and CGP37157,
      which inhibit the Na+/Ca2+ exchanger of isolated mitochondria, could inhibit
      mitochondrial Ca2+ efflux in intact cells; and (ii) whether any sustained
      increase in mitochondrial [Ca2+] ([Ca2+]m) could alter mitochondrial NADH levels.
      [Ca2+]m was measured in Indo-1/AM loaded rat ventricular myocytes where the
      cytosolic fluorescence signal was quenched by superfusion with Mn2+. NADH levels
      were determined from cell autofluorescence. Upon exposure of myocytes to 50 nM
      norepinephrine (NE) and a stimulation rate of 3 Hz, [Ca2+]m increased from 59 +/-
      3 nM to a peak of 517 +/- 115 nM (n = 8) which recovered rapidly upon return to
      low stimulation rate (0.2 Hz) and washout of NE. In the presence of clonazepam,
      the peak increase in [Ca2+]m was 937 +/- 192 nM (n = 5) which remained elevated
      at 652 +/- 131 nM upon removal of the stimulus. CGP37157 in some cells did give
      the same inhibition of mitochondrial Ca2+ efflux as clonazepam, but the effect
      was inconsistent since not all cells were capable of following the stimulation
      rate in presence of this compound. NADH levels increased upon exposure to rapid
      stimulation in the presence of NE alone and recovered upon return to low
      stimulation rates, whereas in clonazepam treated cells the recovery of NADH was
      prevented. We conclude that clonazepam is an effective inhibitor of mitochondrial
      [Ca2+] efflux in intact cells and also maintains the increase in NADH levels
      which occurs upon rapid stimulation of cells.

PMID- 9160169
TI  - The electronic medication event monitor. Lessons for pharmacotherapy.

PMID- 9160170
TI  - The use of other drugs to allow a lower dosage of cyclosporin to be used.
      Therapeutic and pharmacoeconomic considerations.
AB  - Since its discovery in 1970, and introduction into clinical practice in 1978,
      cyclosporin has become the most important immunosuppressive drug used to prevent
      organ transplant rejection. This has been achieved by virtue of the improved
      graft survival rates and adverse effect profiles in patients when compared with
      that of the older agents. Cyclosporin is substantially more expensive (both to
      provide and to monitor) however, and the magnitude of these costs may preclude
      its use, particularly where the transplant recipient is required to pay.
      Cyclosporin has a complex pharmacokinetic profile with poor absorption, extensive
      metabolism to more than 30 metabolites and considerable inter- and intrapatient
      variability. Many transplant centres routinely use drugs ("cyclosporin-sparing
      agents') to allow a reduction in the dosage of cyclosporin while maintaining
      therapeutic blood cyclosporin concentrations. The use of a second drug to affect
      the pharmacokinetic profile of a primary drug is not new, but the use of
      cyclosporin-sparing agents is a departure from previous practices in that this
      coprescription is primarily for economic reasons. The decision to use these
      agents (and the choice of agent) is based upon economic and other factors
      including the extent of the cyclosporin-sparing effect, the potential for
      additional therapeutic benefit and/or adverse effects. The coprescription of
      cyclosporin-sparing agents is ethically more acceptable where the transplant
      recipient is the economic beneficiary but where the savings accrue to a third
      party it is more difficult. Benefits to the community at large must be balanced
      against the risk of adverse effects to the patient. The use of cyclosporin
      sparing agents may reduce compliance and hence, jeopardise transplant and/or
      recipient outcomes. The transplant recipient must be informed about the reasons
      for their use and advised to consult an experienced physician or pharmacist
      before altering the established drug regimen.

PMID- 9160171
TI  - Pharmacokinetic studies with recombinant cytokines. Scientific issues and
      practical considerations.
AB  - Advances in molecular biology and recombinant DNA technology have led to the
      development of cytokines as therapeutic agents for a variety of disease states.
      The pharmacokinetic analysis of cytokines involves the understanding of
      analytical methods capable of detecting these agents in biological fluids and
      recognition of several factors which may have an impact on the cytokine
      concentration-time curves. Enzyme-linked immunosorbent assays (ELISA) have become
      the most common method of detection and commercial kits are available for a wide
      variety of cytokines. Monoclonal antibody products are sensitive, have minimal
      cross-reactivity and are relatively inexpensive when compared with high
      performance liquid chromatography (HPLC). However, the primary limitation of
      these assays is their inability to measure biologically active protein.
      Conversely, bioassays do measure a biological event (i.e. proliferation or
      cytotoxicity) but are generally not used for cytokine analysis because of their
      high cost, long assay completion time, lack of specificity, poor sensitivity and
      influence of environmental conditions on the outcome. The pharmacokinetic profile
      of recombinant cytokines is influenced by a number of variables: endogenous
      production, circulating soluble receptors and cell-associated receptors,
      immunocompetence and antibody production against the cytokine all may influence
      the disposition of the agent. Thus, pharmacokinetic modelling of cytokines may
      involve complex models capable of characterising these nonlinear processes and
      resulting effects. The route of administration is an important variable since
      cytokines administered by subcutaneous injection may be partially metabolised by
      proteases present in the subcutaneous tissue. Other methods to simplify cytokine
      delivery are being actively investigated and include formulations for inhalation,
      topical and oral administration. A variety of cytokines (including interferon
      alpha, interleukin-6 and tumour necrosis factor) are capable of inhibiting
      cytochrome P450 hepatic enzymes and, therefore, possess the potential to cause
      drug-cytokine interactions. Inhibition has been demonstrated in several in vitro
      systems and animal models, although clinical data are currently limited. An
      increased understanding of the many factors which can alter the analysis and
      pharmacokinetics of cytokines is essential to the design of optimal dosage
      regimens.

PMID- 9160174
TI  - HIV and AIDS among the severely mentally ill: introduction to the special series.
AB  - Men and women who have a severe and persistent mental illness are vulnerable to
      infection with HIV. Recognition of this vulnerability led the Office of AIDS at
      the National Institute of Mental Health (NIMH) to invite leading practitioners,
      researchers, consumer advocates, and policy makers to a National Conference on
      HIV and AIDS among the Severely Mentally Ill. This article describes the
      proceedings of the Conference, and provides an overview of the resulting summary
      reports that comprise this special issue.

PMID- 9160172
TI  - Clinical pharmacokinetics of tretinoin.
AB  - Recent reports of the dramatic antitumour effect of tretinoin (all-trans retinoic
      acid) in patients with acute promyelocytic leukaemia (APL) have generated a great
      deal of interest in the use of this drug as a chemopreventive and therapeutic
      agent. However, the biological efficacy of tretinoin is greatly impaired by
      (presumably) an induced hypercatabolism of the drug leading to reduced tretinoin
      sensitivity and resistance. Several pharmacokinetic studies have shown that
      plasma drug exposure [as measured by the plasma area under the concentration-time
      curve (AUC infinity)] declines substantially and rapidly when the drug is
      administered in a long term daily tretinoin regimen. These observations led to
      the hypothesis that the rapid development of acquired clinical resistance to
      tretinoin may have a pharmacological basis and result from an inability to
      present an effective drug concentration to the leukaemic cells during continuous
      treatment. The principal mechanisms proposed to explain the increased
      disappearance of tretinoin from plasma include: (i) decreased intestinal
      absorption; (ii) enhanced enzymatic catabolism; and (iii) the induction of
      cytoplasmic retinoic acid binding proteins (CRABP), which leads to increased drug
      sequestration. The most favoured explanation is that continuous tretinoin
      treatment acts to induce drug catabolism by cytochrome P450 (CYP) enzymes.
      Several strategies aimed at preventing or overcoming induced tretinoin resistance
      have been, and are being, planned. These strategies include intermittent dose
      administration, administration of pharmacological inhibitors of CYP oxidative
      enzymes, combination with interferon-alpha and intravenous administration of
      liposome-encapsulated tretinoin. As these strategies are now under investigation
      and the number of patients enrolled is small, further studies are needed to
      determine the efficacy and toxicity of these new schedules of drug
      administration. In this article we provide an overview of the relevant aspects of
      tretinoin physiology and pharmacokinetics, and summarise the current status of
      knowledge to help in the better optimisation of tretinoin administration.

PMID- 9160175
TI  - Overview of severe mental illness.
AB  - The severe mental illnesses are psychiatric disorders characterized by their
      persistence and extensive disability. Classification of these disorders has seen
      improved reliability, but problems remain with validity. Etiological formulations
      emphasize the biological origins of the disorders, but psychological factors,
      chiefly in the area of stress, are recognized as important in the management of
      relapse. Psychological features, especially those apparent during psychotic
      episodes, make the disorders particularly difficult to treat. Patients tend to be
      noncompliant. In addition, these features dispose people with severe mental
      illnesses to behaviors that place them at risk for HIV and other catastrophic
      illnesses. New psychopharmacological treatments may improve compliance and reduce
      relapse, but none has made psychosocial treatments unnecessary. Progress in
      developing effective treatments has been slow, but prospects are encouraging.

PMID- 9160176
TI  - HIV seroprevalence among people with severe mental illness in the United States:
      a critical review.
AB  - The authors reviewed all studies in the peer-reviewed literature reporting HIV
      seroprevalence among people with severe mental illness in the United States,
      which varied from 4.0% to 22.9%. Findings across samples suggest that
      seroprevalence varies with geographic concentration of HIV and presence of
      comorbid psychoactive substance use disorders, but is consistently high. Unsafe
      sex, drug injection, and noninjected drug use were associated with infection, and
      in most studies women were as likely to be infected as men. Seroprevalence also
      varied with age and ethnicity, but not psychiatric diagnosis. The authors review
      questions and methodological issues important to future studies.

PMID- 9160173
TI  - Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors.
      Similarities and differences.
AB  - Hypercholesterolaemia plays a crucial role in the development of atherosclerotic
      diseases in general and coronary heart disease in particular. The risk of
      progression of the atherosclerotic process to coronary heart disease increases
      progressively with increasing levels of total serum cholesterol or low density
      lipoprotein (LDL) cholesterol at both the individual and the population level.
      The statins are reversible inhibitors of the microsomal enzyme HMG-CoA reductase,
      which converts HMG-CoA to mevalonate. This is an early rate-limiting step in
      cholesterol biosynthesis. Inhibition of HMG-CoA reductase by statins decreases
      intracellular cholesterol biosynthesis, which then leads to transcriptionally
      upregulated production of microsomal HMG-CoA reductase and cell surface LDL
      receptors. Subsequently, additional cholesterol is provided to the cell by de
      novo synthesis and by receptor-mediated uptake of LDL-cholesterol from the blood.
      This resets intracellular cholesterol homeostasis in extrahepatic tissues, but
      has little effect on the overall cholesterol balance. There are no simple methods
      to investigate the concentration-dependent inhibition of HMG-CoA reductase in
      human pharmacodynamic studies. The main clinical variable is plasma LDL
      cholesterol, which takes 4 to 6 weeks to show a reduction after the start of
      statin treatment. Consequently, a dose-effect rather than a concentration-effect
      relationship is more appropriate to use in describing the pharmacodynamics.
      Fluvastatin, lovastatin, pravastatin and simvastatin have similar pharmacodynamic
      properties; all can reduce LDL-cholesterol by 20 to 35%, a reduction which has
      been shown to achieve decreases of 30 to 35% in major cardiovascular outcomes.
      Simvastatin has this effect at doses of about half those of the other 3 statins.
      The liver is the target organ for the statins, since it is the major site of
      cholesterol biosynthesis, lipoprotein production and LDL catabolism. However,
      cholesterol biosynthesis in extrahepatic tissues is necessary for normal cell
      function. The adverse effects of HMG-reductase inhibitors during long term
      treatment may depend in part upon the degree to which they act in extrahepatic
      tissues. Therefore, pharmacokinetic factors such as hepatic extraction and
      systemic exposure to active compound(s) may be clinically important when
      comparing the statins. Different degrees of liver selectivity have been claimed
      for the HMG-CoA reductase inhibitors. However, the literature contains confusing
      data concerning the degree of liver versus tissue selectivity. Human
      pharmacokinetic data are poor and incomplete, especially for lovastatin and
      simvastatin, and it is clear that any conclusion on tissue selectivity is
      dependent upon the choice of experimental model. However, the drugs do differ in
      some important aspects concerning the degree of metabolism and the number of
      active and inactive metabolites. The rather extensive metabolism by different
      cytochrome P450 isoforms also makes it difficult to characterise these drugs
      regarding tissue selectivity unless all metabolites are well characterised. The
      effective elimination half-lives of the hydroxy acid forms of the 4 statins are
      0.7 to 3.0 hours. Protein binding is similar (> 90%) for fluvastatin, lovastatin
      and simvastatin, but it is only 50% for pravastatin. The best characterised
      statins from a clinical pharmacokinetic standpoint are fluvastatin and
      pravastatin. The major difference between these 2 compounds is the higher liver
      extraction of fluvastatin during the absorption phase compared with pravastatin
      (67 versus 45%, respectively, in the same dose range). Estimates of liver
      extraction in humans for lovastatin and simvastatin are poorly reported, which
      makes a direct comparison difficult.

PMID- 9160177
TI  - Risk for human immunodeficiency virus (HIV) infection among persons with severe
      mental illnesses.
AB  - Individuals diagnosed with a severe mental illness are at significantly enhanced
      risk for infection with the human immunodeficiency virus (HIV). To better
      understand elevated seroprevalence in this population, we review the research
      literature that has investigated HIV-related risk behavior among adults who have
      a severe and persistent mental illness. This review indicates that 54%-74% of
      adults report that they have been sexually active in the last year with
      approximately one third reporting two or more partners. Among those who were
      sexually active, condom use was inconsistent. A significant minority (4%-35%) of
      adults also reported a history of injection drug use. Overall, the data indicate
      that the severely mentally ill engage regularly in practices known to involve
      increased risk for HIV transmission. We introduce and modify Fisher and Fisher's
      (1992) theoretical model to organize the possible determinants of HIV-related
      risk taking among severely mentally ill adults, and encourage use of this model
      in the design of behavioral epidemiological and risk reduction studies. We also
      identify several methodological challenges to HIV-related research, including
      problems associated with the use of self-report measures; diagnostic imprecision;
      and participant recruitment and retention.

PMID- 9160178
TI  - HIV risk reduction interventions for persons with severe mental illness.
AB  - Recent seroprevalence studies have shown alarming rates of HIV infection among
      severely mentally ill men and women in large urban areas, and HIV behavioral
      epidemiology research indicates that a substantial proportion of seriously
      mentally ill adults engage in activities that increase their vulnerability to
      HIV/AIDS. In this paper, the research literature on HIV prevention interventions
      is reviewed including reports that have described HIV prevention programs,
      studies that have used uncontrolled pre- and postintervention methods to evaluate
      risk reduction interventions, and those that have used rigorous randomized
      designs and examined risk behavior change. Collectively, these studies show that
      intensive, small-group interventions that target a variety of risk-related
      dimensions-including knowledge, attitudes, and motivations, and behavioral and
      cognitive skills-can produce at least short-term reductions in high-risk sexual
      behavior among the severely mentally ill. A number of gaps in the research
      literature are identified including the need to: (a) better tailor interventions
      to risk situations encountered by the mentally ill; (b) develop gender-tailored
      interventions; (c) examine and implement HIV prevention programs so they help
      persons sustain behavior change; (d) explore one-on-one counseling and community
      level intervention methods; and (e) develop risk reduction interventions for
      already-seropositive individuals. Implications for service provision are
      discussed.

PMID- 9160179
TI  - Severe mental illness and HIV-related medical and neuropsychiatric sequelae.
AB  - Medical and neuropsychiatric sequelae of HIV infection present a spectrum of
      diagnostic and treatment challenges to mental health clinicians. Both HIV and the
      many opportunistic infections that manifest in patients due to their
      immunocompromised state also can affect the central nervous system (CNS). Thus,
      mental health clinicians need to be familiar with the diagnosis and management of
      HIV-related medical and psychiatric complications. This article provides an
      overview of the CNS-related manifestations resulting from HIV disease, including
      HIV-related dementia, psychotic disorders, delirium, CNS opportunistic infections
      and tumors, systemic abnormalities, psychoactive substances, and the adverse
      effects of certain medical treatments. Treatment strategies for individuals with
      HIV disease and comorbid severe mental illness are outlined and recommendations
      for future research are offered.

PMID- 9160180
TI  - Research on HIV, AIDS, and severe mental illness: recommendations from the NIMH
      National Conference.
AB  - We summarize the recommendations for research that emerged from a NIMH-sponsored
      Conference on HIV, AIDS, and Severe Mental Illness. Recommendations are made in
      four areas, namely, epidemiology of HIV infection, epidemiology of sexual and
      drug-use risk behaviors, risk reduction and transmission prevention, and
      treatment of infected persons. This research is urgently needed to adequately
      respond to the AIDS epidemic among people with severe mental illness.

PMID- 9160181
TI  - Securing biotechnological resources--the place of the resource centre.

PMID- 9160182
TI  - Direct molecular genetic diagnosis and heterozygote identification in X-linked
      Emery-Dreifuss muscular dystrophy by heteroduplex analysis.
AB  - X-linked Emery-Dreifuss muscular dystrophy (EMD) is a very rare, relatively
      benign muscle disorder. The disease is associated with potentially lethal cardiac
      arrhythmias in affected males and some heterozygous females. X-linked EMD can be
      genetically distinguished from phenotypically similar autosomal EMD. Heterogenic
      mutations are identified as the cause of X-linked EMD. We introduced heteroduplex
      analysis to follow the segregation of heterogenic emerin gene mutations in the
      families of six unrelated EMD patients. Heteroduplex analysis was proved to be a
      simple, fast and reliable tool for direct molecular genetic diagnosis of EMD in
      male patients and identification of heterozygotes even in families where affected
      males are not available as index cases.

PMID- 9160183
TI  - TaqI polymorphism in the 3' flanking region of the PI gene among Kuwaiti Arabs
      and Russians.
AB  - The Taq1 polymorphism in the 3' flanking region of the PI gene has been reported
      to be associated with chronic obstructive pulmonary disease (COPD). We have
      studied the frequency of the Taq1 polymorphism in 117 Kuwaiti Arabs and 110
      Russians using PCR/RFLP. The frequency of this polymorphism was found to be 0.235
      in the Arabs and 0.027 in the Russians. Such a striking difference in allele
      frequencies could be due to a 'founder effect' in the Kuwaiti population.
      However: it may also be that this mutation provides a selective advantage, thus
      accounting for its fixation at a rather high frequency in some populations. Our
      results suggest that ethnic composition is a very important factor which should
      be taken into consideration when studying the association of the Taq1
      polymorphism with COPD.

PMID- 9160184
TI  - Family and twin studies in systemic lupus erythematosus.
AB  - We have estimated how much of the total genetic predisposition to SLE may be
      attributable to genes outside the HLA region by comparing figures for concordance
      of SLE in monozygotic twins with those for concordance in HLA identical siblings
      in Australia. None of six dizygotic co-twins of white Australian SLE probands was
      concordant for SLE. One of four (25%) monozygotic co-twins of white Australian
      SLE probands was concordant for SLE which when added to previously published
      figures for Caucasoid populations gives an overall concordance rate for SLE in
      monozygotic twins of 25%. None of 18 HLA identical, same sex siblings of SLE
      probands, had definite SLE by the study criteria (i.e. less than 6%). The
      comparison of these figures shows that most of the genetic predisposition to SLE
      is attributable to genes outside the HLA region.

PMID- 9160185
TI  - Molecular analysis of androgen resistance syndromes in Egyptian patients.
AB  - Androgen resistance syndromes [i.e. 5 alpha-reductase deficiency (5 alpha RD) and
      androgen receptor (AR) defects] are frequently reported among Egyptian intersex
      patients. This study examined AR and 5 alpha-reductase 2 (5 alpha R2) gene
      mutations among a sample of such cases as a first step towards instituting a
      screening program. Five families with a typical hormonal profile of 5 alpha RD
      were screened for major deletions of exons 3-5 of the 5 alpha R2 gene, using
      polymerase chain reaction (PCR) and electrophoresis. Thereafter, screening for
      point mutations was carried out by single strand conformational polymorphism
      (SSCP) analysis, followed by nucleotide sequencing. Seven patients with androgen
      insensitivity syndrome (AIS) were subjected to molecular analysis of AR exons B-H
      by a similar protocol, except for the use of denaturing gradient gel
      electrophoresis (DGGE) for screening point mutations. No major deletions were
      found in either gene. One family had abnormal electrophoretic mobility on SSCP of
      exon 5 of the 5 alpha R2 gene, resulting from a point mutation (C to T
      substitution) at codon 246. Another family, showing retarded mobility on DGGE,
      had a point mutation (G to A substitution) at codon 889 of the AR gene. In
      conclusion, the study revealed two mutations previously reported in other
      geographically distinct populations, inferring the possibility of mutational hot
      spots in the genes.

PMID- 9160186
TI  - Altered endometrial progesterone/oestrogen receptor ratio in luteal phase defect.
AB  - The total oestrogen and progesterone receptor levels (TER, TPR) were measured in
      endometrial biopsy samples of 10 infertile patients with luteal phase defect
      (LPD) and compared to those of controls. Serum levels of progesterone (P),
      obtained in the luteal phase, were also measured. Midluteal phase P values were
      significantly decreased in LPD cycles; however some overlap of values existed.
      LPD cycles had significantly lower endometrial TER and TPR concentrations than
      did control cycles. TPR/TER ratio was found to be a reliable test for diagnosis;
      having a sensitivity, and specificity of 90% and the odds ratio of 81. The
      TPR/TER ratio for inphase endometria ranged between 1.13 and 58.22, with 95%
      confidence. It seems that abnormal folliculogenesis, as a cause of LPD, results
      in wide ranges of endometrial TER and TPR concentrations, yet with well defined
      alteration in TPR/TER ratio. Summation of the results of the present study along
      with those previously reported, indicates that TPR/TER ratio may be of great
      value in characterisation of a well defined endometrial receptor imbalance in
      luteal phase defect, whatever the underlying aetiology.

PMID- 9160187
TI  - HLA antigens in microscopic polyarteritis (MP) with renal involvement.
AB  - Serological HLA-A, B, C, DR and DQ typing was performed in 23 patients with
      microscopic polyarteritis and renal involvement and in 405 healthy individuals,
      all of Greek origin. An increased frequency of HLA-A26 (26% vs. 11.3%, x2 =
      4.423, p < 0.05) and HLA-A11 (26% vs. 9.6%, x2 = 6.825, P < 0.02), and a
      decreased frequency of HLA-DR3 (4.3% vs. 24.1%, x2 = 5.935, p < 0.025) were
      found. Five out of six patients, who did not respond to treatment possessed HLA
      DR5. These observations suggest that HLA gene products may influence the clinical
      expression, as well as the outcome of this disease.

PMID- 9160188
TI  - HLA class I phenotype and gene frequencies in parts of southern Nigeria.
AB  - HLA-A, B and C antigens were determined in 101 healthy subjects from two major
      and several minor ethnic groups in some parts of Southern Nigeria. Compared to
      earlier data based on a panel of expatriate Nigerians, significant differences
      were observed in antigen phenotype and gene frequencies particularly at the HLA-A
      locus. At least three antigenic specificities not previously observed in the
      expatriate Nigerians were detected in the present study. These included HLA-B8.
      B14 and CW1. These antigens however occurred at low frequencies. The antigens A23
      and B7 were in positive linkage disequilibrium along with others which involved
      CW4 with B53 or B35. It is concluded from our findings that HLA polymorphisms in
      Nigerians may not be completely reflected in major population group studies
      alone. It is possible that more specificities may be detected by continued
      testing of the minor ethnic groups. The importance of this could be immense in
      disease association studies involving HLA genes as well as in anthropology.

PMID- 9160190
TI  - Identification of human papilloma virus DNA sequence in the hyperplastic
      epithelium of an oral denture fibroma.
AB  - The human papilloma virus (HPV) associated with hyperplastic epithelium in an
      oral denture fibroma was examined by southern blot hybridization. Extracted DNA
      was hybridized with full length linear HPV type 2a, 6b, 11, 16, 18, 31 and 33
      DNAs as a mixed probe only under low stringent conditions. The hybridized bands
      digested with Bam HI and Eco RI were approximately 8.8 kbp and 15 kbp,
      respectively. Thus the lesional HPV DNA was different from HPV types used as
      probes and was probably integrated into host cell chromosomal DNA judging by the
      off-size high molecular weight bands. Considering the contaminating mesenchymal
      region and uninfected epithelial cells as well as the evidently limited homology
      with probe HPV DNAs, the virus copy number in infected cells was poorly defined.
      In situ antigen staining signals were widely detected in the hyperplastic
      epithelial layer.

PMID- 9160189
TI  - Rapid testing for the MCAD G583A mutation, by PCR-mediated site directed
      mutagenesis, in an Australian population of SIDS patients.
AB  - Medium Chain Acyl CoA Dehydrogenase (MCAD) deficiency is the most common genetic
      disorder of fatty acid metabolism and has been reported as a cause of sudden
      death in infants. We investigated the incidence of a rare MCAD mutation (G583A)
      in a large population of SIDS patients. A method utilising PCR mediated site
      directed mutagenesis and restriction enzyme digestion was devised to enable rapid
      and simple testing of large numbers of samples. The G583A mutation was not
      detected in 413 SIDS patients tested suggesting the mutation is not an important
      cause of sudden death in infants. The prevalence of this mutation in the general
      population was estimated to be between 0 and 0.89%.

PMID- 9160191
TI  - Economic analysis of dyspepsia.
AB  - A variety of organic and non-organic diseases can present with symptoms of
      dyspepsia or upper abdominal pain, and a large diagnostic and therapeutic
      armamentarium is available to manage symptoms of dyspepsia. How extensively
      should a diagnostic search be conducted; and where does the best path run through
      the maze of potential combinations of tests and therapies? Physicians have hoped
      that economic and medical decision analyses would help them to find the most cost
      effective and most efficacious means to deal with dyspepsia. Because of the large
      variety of potential diagnoses, diagnostic procedures and therapeutic means,
      however, it is very doubtful that a single most effective or least expensive
      strategy can ever be developed to apply to every patient with dyspepsia.
      Following the lines of common medical sense is probably more cost-effective than
      observing a rigid regimen derived from an economical analysis.

PMID- 9160193
TI  - Chronic inflammatory bowel disease: uniformity or diversity of impact in Europe.

PMID- 9160192
TI  - Irritable bowel syndrome and sexual/physical abuse history.
AB  - There is growing evidence that a history of sexual or physical abuse can affect
      emotional and physical well-being. Within gastroenterology, attention has focused
      on the increased frequency of abuse history, particularly for patients with
      refractory functional gastrointestinal (GI) disorders. Furthermore, regardless of
      diagnosis, abuse history can impair health status and one's ability to cope with
      one's medical condition. Especially for patients with painful functional GI
      disorders resistant to usual treatments, the physician should inquire in a
      supportive manner about the possibility of a prior abuse history or other
      psychosocial traumas (e.g., major loss). This can then lead to an appropriate
      mental health referral (along with continued medical care) and an improved
      clinical outcome.

PMID- 9160194
TI  - Helicobacter pylori and acid secretion: where are we now?
AB  - It is now widely recognized that H. pylori gastritis can produce marked
      alterations in gastric acid secretion. In subjects with an antral predominant
      gastritis there is increased release of gastrin and consequently increased acid
      secretion. Such subjects are at risk of developing duodenal ulcers. In other
      subjects the infection produces a marked body gastritis and this is associated
      with marked hyposecretion of acid or complete achlorhydria. These subjects have
      an increased risk of developing gastric cancer. Between these two ends of the
      disease spectrum lie the majority of H. pylori-infected subjects who have
      gastritis of both the antrum and body and no overall change in acid secretion.
      The reason why the infection exerts these divergent effects on gastric morphology
      and function remains unclear and is a challenge for ongoing research.

PMID- 9160195
TI  - The Omega-Project--a comparison of two diagnostic strategies for risk- and cost
      oriented management of dyspepsia.
AB  - OBJECTIVES: In dyspepsia few data are available from the primary care setting on
      how selective, risk-factor-oriented endoscopy compares with mandatory endoscopy
      in the diagnostic outcome and in direct and secondary costs. We studied this in a
      two-armed multicentre trial (omega-project) with primary care physicians.
      MATERIAL AND METHODS: Patients were enrolled and treated by primary care
      physicians and referred to a gastroenterologist for upper gastrointestinal
      endoscopy (UGE). Patients were enrolled in the study if they had had epigastric
      complaints for more than 1 month and no obvious signs or history of organic
      disease. In the first arm of the study endoscopy was mandatory, in the second
      selective, i.e. according to a predefined risk profile. Patients enrolled were
      treated with prokinetic drugs for 2 months. A further indication for endoscopy
      was non-response to treatment (reduction of the initial symptoms score by less
      than two-thirds) in the study with selective endoscopy and relapse within the 2
      month follow-up period in both studies. The direct costs from number of
      consultations with the primary care physician, UGEs, number of prescriptions per
      patient and also absenteeism in days per week were carefully registered in both
      groups. RESULTS: All 172 patients of the mandatory endoscopy study and 203/656
      patients enrolled in the selective endoscopy study had an UGE (125 at admission,
      78 in the follow-up period). Patients were treated for 4 weeks (cisapride or
      domperidone) and thereafter followed for 8 weeks, at the end of the observation
      period the response rates were 80% and 79%, respectively. The prevalence of
      gastric cancers was similar in both groups (> 1%) but extrapolation from the data
      collected with compulsory endoscopy suggests that two-fifths of the anticipated
      peptic lesions remained undetected by following the selective strategy. The cost
      analysis revealed a 31% cost reduction with the selective strategy--in the Swiss
      cost system--through a reduction in the number of endoscopies by 67%. CONCLUSION:
      Selective UGE is cheaper and appears not to compromise the response to
      prokinetics; however, its diagnostic power is less than with mandatory UGE.

PMID- 9160196
TI  - Sexual abuse is more frequently reported by IBS patients than by patients with
      organic digestive diseases or controls. Results of a multicentre inquiry. French
      Club of Digestive Motility.
AB  - OBJECTIVES: The aim of this multicentre inquiry was to evaluate the prevalence of
      sexual abuse among IBS patients consulting a gastroenterologist, in comparison to
      healthy controls and patients with organic digestive diseases. PATIENTS AND
      METHODS: Patients with irritable bowel syndrome (IBS; Rome Criteria) were
      included by eight university hospitals (n = 196; 41.2 +/- 20.6 years; sex ratio
      (M/F) = 0.23). Control groups were: (i) patients consulting for the follow-up of
      non-neoplastic organic digestive diseases (n = 135; 41.5 +/- 17.0 years; 1.21);
      (ii) patients attending ophthalmology units (n = 200; 43.8 +/- 20.7 years; 0.81);
      (iii) healthy subjects seen in centres of the National Health System (n = 172;
      40.3 +/- 16.3 years; 0.83). Each patient filled in an anonymous questionnaire,
      without help. Prevalence of sexual abuse in the various groups was compared by
      the chi 2 test. RESULTS: Sixty-two instance of sexual abuse (55 females, 7 males)
      were recorded among the 196 IBS patients (31.6%); 8 cases of verbal aggression, 4
      of exhibitionism, 11 of sexual harassment, 22 sexual touches, 17 rapes. The
      prevalence of sexual abuse was 14.0% for the patients with organic digestive
      diseases (P = 0.0005 vs. IBS), 12.5% among ophthalmology patients (P < 0.0001)
      and 7.6% in healthy controls (P < 0.0001). Sexual abuse was accompanied by
      physical abuse in 23 IBS patients and 19 patients from control groups (not
      significant). Twenty-six IBS patients reported isolated physical abuse (14.7%)
      versus 40 from control groups (8.8%; P = 0.041). There was a significant trend
      towards more severe attacks of abuse among IBS patients than in others.
      CONCLUSION: This study confirms the high prevalence of sexual abuse among IBS
      patients consulting in Gastroenterology. Some of these patients would benefit
      from appropriate therapy. (In the majority of cases, this will be psychotherapy.)

PMID- 9160197
TI  - Clinical uniformity of inflammatory bowel disease a presentation and during the
      first year of disease in the north and south of Europe. EC-IBD Study Group.
AB  - OBJECTIVE: To compare the methods used for diagnosis and the clinical features of
      non-specific inflammatory bowel disease (IBD) in the north and south of Europe.
      DESIGN: A prospective study over 2 years in 1991-3 at eight centres in the north
      and 12 in the south of Europe using the same criteria for disease definition and
      same protocol for recording data. SETTING: Specialist gastroenterological centres
      with good diagnostic facilities at which every effort was made to ascertain all
      new cases of IBD seen in other departments and primary care in a defined
      geographical area of known population. PARTICIPANTS: A total of 2201 patients
      newly diagnosed as suffering from IBD, 1397 with ulcerative colitis (UC), 706
      with Crohn's disease (CD) and 116 with indeterminate colitis (IND). RESULTS:
      Diagnostic methods used were similar in north and south, a biopsy or resection
      specimen was available for examination in 94 and 95%, of cases of UC and 92 and
      87% of CD in north and south, respectively. The type, clinical presentation, site
      and extent of disease were similar in north and south. Treatment followed a
      common pattern and mortality from IBD was low in the first year after diagnosis.
      In both areas, age of onset of UC tended to be later than CD. CONCLUSION: The
      standard of diagnosis and clinical features of IBD are similar in specialist
      centres throughout Europe so providing a valid basis for this aspect of
      collaborative epidemiological or other studies.

PMID- 9160200
TI  - Helicobacter pylori infection after partial gastrectomy for peptic ulcer and its
      role in relapsing disease.
AB  - OBJECTIVE: To elucidate the role of Helicobacter pylori in relapsing disease
      after partial gastrectomy for peptic ulcer. DESIGN: Retrospective study of
      gastroscopies between January 1985 and February 1988. SETTING: Department of
      Surgery, Helsinki University Central Hospital, Finland. PARTICIPANTS: One hundred
      and fifty-five patients, who had undergone partial gastrectomy for peptic ulcer
      disease. MAIN OUTCOME MEASURES: Correlation between clinical and laboratory data,
      macroscopic findings at gastroscopy and histopathology. RESULTS: At gastroscopy
      41 patients showed an ulcer at the site of anastomosis or in the gastric stump
      and two patients had a history of a previous ulcer recurrence. The median time
      interval between operation and relapse was 4 years. There was no correlation
      between ulcer recurrence, sex, age, ABO blood group or other diseases. Smokers
      and patients using non-steroidal anti-inflammatory drugs (NSAIDs) or alcohol had
      more relapses, but the difference was not significant. The recurrence rate was
      higher after Billroth II (BII; 34%) than after Roux-en-Y (14%; P = 0.03) or
      Billroth I (BI) reconstruction (24%). Giemsa staining demonstrated H. pylori in
      the gastric stump of 37% of the patients. H. pylori expression was related to age
      but unrelated to sex, ABO blood group, NSAID use, smoking or alcohol consumption.
      H. pylori positivity was more common (52%) after BI than after BII (28%; P =
      0.04) or Roux-en-Y resection (40%). Recurrent ulcer was more often found in
      gastric remnants with normal mucosa (36%) than in those with H. pylori-positive
      gastritis (18%; P = 0.03) or H. pylori-negative gastritis (26%). CONCLUSION: It
      seems that H. pylori infection plays a minor role in the pathogenesis of ulcer
      recurrence after partial gastrectomy for peptic ulcer disease. Eradication of H.
      pylori of the remnant stomach is therefore presumably not effective in preventing
      ulcer recurrence.

PMID- 9160198
TI  - Antral and fundic D-cell numbers in Helicobacter pylori infection.
AB  - OBJECTIVES: Helicobacter pylori infection is associated with an exaggeration of
      gastrin release following meals or bombesin stimulation attributed to a defect of
      somatostatin secretion of antral D-cells. Nevertheless, these modifications of
      gastric physiology do not explain the increase of gastric acid secretion which is
      only observed in duodenal ulcer patients. The inhibitory effect of somatostatin
      secretion of fundic D-cells on parietal cells is well known. The aim of our
      prospective study was to compare the number of fundic D-cells and likewise the
      number of antral G-cells and D-cells between patients with duodenal ulcer and
      healthy subjects with and without H. pylori infection. METHODS: The numbers of D
      cells and G-cells were compared between 19 infected patients with duodenal ulcer
      and 20 healthy subjects, 10 with and 10 without H. pylori infection. Fundic
      mucosal biopsy specimens were examined using immunohistochemical techniques
      specific for the presence of somatostatin, antral mucosal biopsy specimens for
      the presence of gastrin and somatostatin. RESULTS: The number of G-cells was
      significantly lower (P = 0.0012) in duodenal ulcer patients by comparison with
      infected subjects and controls. The number of antral D-cells was significantly
      less (P < 0.0001) in duodenal ulcer patients (mean of 10 random fields = 0.45 +/-
      0.04) than in either asymptomatic infected patients (0.65 +/- 0.07) or uninfected
      controls (0.88 +/- 0.10). The number of fundic D-cells was significantly lower (P
      < 0.0001) in duodenal ulcer patients (mean = 0.20 +/- 0.03) than in either
      asymptomatic infected subjects (0.29 +/- 0.05) or controls (0.73 +/- 0.09); here
      the difference between the two groups of infected subjects was not significant.
      Multivariate analysis showed that the presence of H. pylori infection of the
      fundic mucosa did not influence the number of fundic D-cells. CONCLUSION: Changes
      in the number of fundic and antral D-cells induced by H. pylori infection did not
      explain abnormalities of gastric acid secretion usually observed in duodenal
      ulcer patients; it is suggested that pre-existing abnormalities in the regulation
      of parietal cell or increase of parietal cell mass are involved.

PMID- 9160199
TI  - The Helicobacter pylori seroprevalence in blood donors related to Lewis (a,b)
      histo-blood group phenotype.
AB  - OBJECTIVE: To study a possible association of the Helicobacter pylori
      seroprevalence with ABO(H) and Lewis (a,b) blood group phenotypes in blood
      donors. DESIGN: A cross-sectional study of blood donors using ABO(H) and Lewis
      (a,b) blood group phenotype as predictors. METHODS: ABO(H) and Lewis (a,b) blood
      group phenotyping was performed with monoclonal antibody. The H. pylori
      immunoglobulin G (IgG) antibody relative activity was evaluated by enzyme-linked
      immunosorbent assay (ELISA) using acid glycine extract from H. pylori. SUBJECTS:
      One hundred and fifty-nine randomly selected blood transfusion donors. RESULTS:
      The individuals with Lewis (a+b-)/non-secretor phenotype showed a significantly
      higher proportion of the H. pylori-seronegative subjects and a lower IgG immune
      response to H. pylori antigens as compared with the individuals of Lewis (a
      b+)/secretor phenotype. CONCLUSION: The Lewis (a,b) histo-blood group antigens
      are implicated in the mechanisms of naturally occurring resistance to H. pylori
      infection.

PMID- 9160201
TI  - The relationship between juxtapapillary duodenal diverticula and biliary stone
      disease.
AB  - OBJECTIVE: To assess the relationship between juxtapapillary duodenal diverticula
      (JDD) and common bile duct stones and biliary stone disease in general. DESIGN: A
      retrospective study. METHODS: We analysed 1115 patients who underwent consecutive
      endoscopic retrograde cholangiopancreatography examinations. The patients were
      subdivided into three groups: the first group (group I; n = 482) had no biliary
      stone disease, the second one (group II; n = 329) had common bile duct stones,
      and the third group (group III; n = 304) had biliary stone disease of the
      gallbladder but without evidence of common bile duct stones. Additionally, the
      patients were subdivided into age groups of < 50, 50-59, 60-69, 70-79, and > or =
      80 years of age. Logistic regression was applied for statistical analysis.
      RESULTS: Juxtapapillary duodenal diverticula were diagnosed in 111 (10.0%)
      patients. The incidence of JDD was 6.9% in group I, 14.3% in group II and 10.2%
      in group III. Age was the most dominant influence factor for JDD, common bile
      duct stones, and biliary stone disease (P < 0.0001). Sex was also a factor,
      female patients having a higher risk for common bile duct stones (P = 0.01) and
      biliary stone disease (P < 0.0001). After adjustment for age and sex, JDD was
      found to have a noticeable, but not statistically significant (P = 0.073),
      influence on common bile duct stones and no influence on biliary stone disease (P
      = 0.15). CONCLUSION: Our data support only moderately the existence of a
      relationship, which had been conjectured in a part of the literature, between JDD
      and common bile duct stones. No noticeable influence on biliary stone disease was
      found.

PMID- 9160202
TI  - Disturbances in the propagation of the slow wave during acute local ischaemia in
      the feline small intestine.
AB  - OBJECTIVE AND DESIGN: The normal aborad propagation of the slow wave in the small
      intestine is easily distorted by pacing, hypoxia or transection. We studied
      whether acute local ischaemia would also induce serious conduction disturbances
      and ectopic pacemaking. METHODS: After general anaesthesia and a mid-abdominal
      incision, a multi-electrode array of 240 extracellular electrodes was positioned
      on the serosal surface of an exteriorized intestinal loop. Simultaneous
      recordings of all 240 surface electrodes was performed during a control period
      and for 5-10 min following local acute arterial occlusion. After the experiments
      activation maps were constructed describing the pattern of propagation of the
      slow waves. RESULTS: During control periods, the activation maps showed
      homogeneous aborad conduction of the slow wave. During acute ischaemia, local
      areas of inexcitability developed rapidly, merging together to form lines of
      conduction block. This in turn often provoked the appearance of subsidiary
      ectopic pacemakers. The location of the conduction blocks as well as that of
      ectopic pacemakers was highly variable and could disappear and reappear at other
      sites. CONCLUSION: Within minutes, acute ischaemia disturbed the organized
      homogeneous aborad propagation of the slow wave leading to pronounced
      inhomogeneous depression of conduction, local inexcitability, conduction block
      and the appearance of subsidiary pacemakers.

PMID- 9160203
TI  - Helicobacter pylori: clarifying the issues and curing the disease.
AB  - This paper summarizes the presentations and discussions at a recent meeting on H.
      pylori infection attended by gastroenterologists from around Europe and North
      America. The meeting was sponsored by Abbott Laboratories International Division.

PMID- 9160204
TI  - Two young Somalians with gastric outlet obstruction as a first manifestation of
      gastroduodenal tuberculosis.
AB  - Gastroduodenal tuberculosis (GDTB) is an uncommon condition which can mimic other
      gastrointestinal disorders. It usually occurs secondary to pulmonary
      tuberculosis. We describe two young Somalian patients who presented with
      abdominal pain and gastric outlet obstruction. GDTB was diagnosed in both
      patients and they were successfully treated with antituberculous drugs.

PMID- 9160205
TI  - Intraluminal duodenal diverticulum causing recurrent acute pancreatitis: case
      report and review of the literature.
AB  - Intraluminal duodenal diverticulum-(IDD) is a rare congenital anomaly. Only 16
      cases of acute pancreatitis complicating IDD have been reported in the world
      literature. We present one additional case discuss the pathogenesis, clinical and
      radiological features as well as the treatment, and review the literature.

PMID- 9160206
TI  - Tenoxicam-associated hepatic injury: a case report and review.
AB  - A 51-year-old woman developed jaundice while taking tenoxicam. A full evaluation,
      including ultrasound, computed tomography, endoscopic cholangiography and liver
      biopsy, confirmed the diagnosis of mixed hepatic injury. The patient's jaundice
      and all other liver function abnormalities normalized 1 month after she
      discontinued taking tenoxicam. This is the first case report of mixed hepatic
      injury, confirmed with biopsy, associated with tenoxicam. Tenoxicam should be
      considered as a potential cause of hepatic injury when other more common
      aetiologies have been excluded.

PMID- 9160207
TI  - Use of extracorporeal liver assist device and auxiliary liver transplantation in
      fulminant hepatic failure.
AB  - The case history of a 14-year-old boy with fulminant hepatic failure secondary to
      non-A, non-B hepatitis who fulfilled selection criteria for orthotopic liver
      transplantation is described. Two forms of liver support were used
      (extracorporeal liver assist device and an auxiliary partial orthotopic liver
      transplantation) to provide additional time to allow spontaneous recovery to
      occur. During the 66 h of extracorporeal haemoperfusion through the device,
      haemodynamic stability was maintained along with improvements in serum bilirubin
      (555 to 381 mumol/l), and international normalized ratio (INR) (3.7 to 2.9).
      Deterioration in these parameters was observed following cessation of treatment
      and 10 h later, after a donor liver had become available, an auxiliary transplant
      was performed. Clinical recovery, though initially slow, was eventually complete,
      with histopathological and scintigraphic evidence of full liver regeneration at 3
      months. Withdrawal of his immunosuppressive drugs began at 6 months and was
      complete by 14 months after auxiliary transplantation. He has since remained well
      with normal liver function tests. Temporary liver support may provide additional
      time for spontaneous recovery of the native liver to occur in selected cases of
      fulminant hepatic failure, even when criteria are fulfilled for orthotopic liver
      grafting.

PMID- 9160208
TI  - Is the Glasgow Dyspepsia Severity Score a tool for the global measurement of
      dyspepsia?

PMID- 9160209
TI  - Heterogeneity of Helicobacter pylori.
AB  - Although many physicians view Helicobacter pylori strains as a homogenous group
      of organisms, it has become increasingly clear that populations in humans are
      highly diverse. This heterogeneity can be analyzed at two different levels:
      genotypic variation among strains and variations in H. pylori populations within
      an individual host. Genotypic variation includes point mutations in conserved
      genes (e.g. ureC), variation in the gene order on physical maps, mosaicism in
      conserved genes (e.g. vacAs1a), non-conserved genes (e.g. cagA) and extragenetic
      elements (e.g. IS605). Population differences include the observations that
      humans can be simultaneously infected with two or more H. pylori strains and that
      a single strain may represent a cluster of closely related organisms (a
      'quasispecies'). The presence of multiple organisms within a host may occur as a
      result of recombination events leading to genetic shift, whereas ongoing mutation
      within a strain can lead to the formation of quasispecies by genetic drift. Over
      recent years it has become increasingly clear that observations on the
      fundamental biology of H. pylori have considerable clinical relevance. Several
      genotypic markers (e.g. cagA, vacA, sIa and iceA1) are associated with an
      increased risk of disease. Also, the multiplicity of infection and quasispecies
      indicates that analysis of a single H. pylori isolate is inaccurate for defining
      the genotype of H. pylori strains present in a patient. Global assays, such as
      serology, are more suitable. The aim of this paper is to review the general
      phenomenon of diversity in H. pylori and to describe particular heterogeneities
      that are related to clinical outcome.

PMID- 9160210
TI  - Pathophysiology of duodenal ulcer disease.
AB  - Before the discovery of Helicobacter pylori infection some 12 years ago, three
      major disturbances in gastric physiology had been identified in patients with
      duodenal ulcer disease. These abnormalities were: impaired acid inhibition of
      gastrin release from the antral mucosa, increased basal and stimulated acid
      secretion by the body of the stomach and increased acid load in the duodenum.
      Some of these abnormalities in gastric function can now be explained by the
      effects of H. pylori infection. The increased release of gastrin by the antral
      mucosa in duodenal ulcer patients, for example, can be entirely explained by the
      effects of this organism. Other abnormalities, however, appear to have a genetic
      basis or may be due to environmental factors. Much work has been conducted on the
      relationship between H. pylori and the development of duodenal ulcer disease and
      this paper aims to review recent studies in the field and to give an overview of
      the latest understanding of the pathophysiology of this disease.

PMID- 9160211
TI  - The most important diagnostic modalities for Helicobacter pylori, now and in the
      future.
AB  - CURRENT DIAGNOSTIC METHODS: Helicobacter pylori infection plays a central role in
      the pathophysiology of gastrointestinal disease, and its accurate diagnosis and
      successful eradication is crucial in a wide range of different circumstances.
      Currently, serology is recommended for initial screening, followed by histology
      and/or culture to confirm the diagnosis before treatment. Since H. pylori is
      developing greater resistance to certain antibiotics, culture is becoming
      increasingly important in some populations to test for susceptibility to
      antibiotics. To confirm eradication after treatment, the urea breath test is
      used. This test is presently the best non-invasive test to determine eradication.
      NEW APPROACHES: Considerable efforts are being made to improve diagnostic
      methods, and a host of new or improved approaches can be expected in the near
      future. For general screening, tests are being developed that use whole blood and
      can be used by general practitioners to give rapid results in a cost-effective
      manner. The evidence so far suggests that these new 'office' tests are not as
      accurate as laboratory tests, but they are nevertheless important for general
      diagnostic purposes. Serological tests for cagA antibodies and immunoblot tests
      are also under development. New biopsy-based tests include the development of a
      true rapid urease test which will give accurate results in 1 h. Polymerase chain
      reaction/DNA enzyme immunoassay detection is another field receiving attention.
      Non-invasive direct tests of the future are likely to include the use of the
      polymerase chain reaction in faeces. This paper reviews current diagnostic
      modalities for H. pylori and gives an overview of expected future developments.

PMID- 9160212
TI  - Management of Helicobacter pylori-related disorders.
AB  - The discovery of Helicobacter pylori has opened new opportunities in the
      management of gastrointestinal disorders, with the cure of chronic ulcer disease
      now being possible for the first time. The 1994 United States National Institutes
      of Health Consensus Conference recommended that patients with duodenal or gastric
      ulcers unrelated to the use of non-steroidal anti-inflammatory drugs (NSAID)
      should be given eradication therapy. These guidelines were refined at a
      conference held recently in Maastricht. The updated guidelines strongly recommend
      treatment in patients with duodenal or gastric ulcer disease, low-grade mucosa
      associated lymphoid tissue (MALT) gastric lymphoma, gastritis with severe macro-
      or microscopic changes and after resection of early gastric cancer. Despite a
      lack of hard scientific evidence, the guidelines also suggest that eradication
      treatment is advisable in patients with unequivocally diagnosed functional
      dyspepsia, a family history of gastric cancer, long-term treatment with proton
      pump inhibitors for gastro-oesophageal reflux disease (GORD), planned or existing
      NSAID treatment, after gastric surgery for ulcer or cancer, or if the patient
      wants to be treated. Many different therapeutic regimens have been used
      previously, but at present the best treatment is proton-pump inhibitor-based
      triple therapy, comprising a proton-pump inhibitor plus two drugs out of
      clarithromycin, a nitroimidazole and amoxycillin. One-week low-dose triple
      therapy cures 85-95% of infected patients.

PMID- 9160213
TI  - Economics of Helicobacter pylori eradication therapy.
AB  - The annual incidence of peptic ulcer disease in developed countries is around one
      to three per thousand inhabitants. Since the introduction of acid-secretion
      inhibitors, the indirect costs of this disease, which has a high rate of relapse,
      have steadily decreased, although direct costs have been increasing. The
      possibility of healing the patient through Helicobacter pylori eradication has
      the potential for a huge economic impact considering the long-term cost: benefit
      ratio. A recent study has shown that H. pylori eradication therapy can save
      between US$750,000 and US$1,000,000 per year per million inhabitants in western
      Europe compared to maintenance or episodic therapy. This paper reviews the cost
      implications of various management strategies for peptic ulcer disease, comparing
      the cost: benefit ratios of five different treatment regimens.

PMID- 9160214
TI  - The aging skin.
AB  - In the past, sun exposure has been an integral part of the American life style.
      Along with increased leisure time, outdoor recreational sports, and sun bathing
      has come greater exposure to the sun. The cumulative effects of unprotected sun
      exposure coupled with the changes in the ozone layer have resulted in a large
      photodamaged population and an epidemic of the most dangerous skin cancer,
      malignant melanoma. Photodamage begins early, with a child's first unprotected
      sun exposure. Clinical studies show that 50% of an individual's ultraviolet light
      exposure occurs before the age of 18 years. This damage from acute and chronic
      ultraviolet light exposure has produced the explosion of skin cancers. Over the
      next 4 years, it is expected that skin cancer will become the most common type of
      cancer, and malignant melanoma will become the leading cause of death from skin
      cancer. This growing hazard to the public has profound medical and psychological
      ramifications. This paper will focus on prevention, identification, evaluation
      and treatment of photodamage to skin, as well as skin cancer. Special emphasis
      will be given to the National Skin Cancer Prevention Education Program.

PMID- 9160216
TI  - Affective spectrum disorders: how to recognize and treat depression.
AB  - Depression often goes undiagnosed. Even when pharmacotherapy is initiated, many
      patients discontinue therapy and thus risk relapse. Depression may occur at any
      age; however, the average age of onset is the late twenties. Acronyms have been
      developed to help the clinician recognize depression in the clinical setting.
      Common medications, abused substances, and medical disorders may cause and/or
      mimic depression. If pharmacotherapy is deemed appropriate, the choice of
      antidepressant is based on personal/family history of response to a particular
      agent and the side effect profile of the agent, as well as suicide risk. The
      tricyclic antidepressants and monoamine oxidase inhibitors are associated with
      anticholinergic effects, orthostasis, and risk of death in overdose. The
      selective serotonin reuptake inhibitors may have more tolerable adverse effects.
      Newer agents have also been marketed; however, the selective serotonin reuptake
      inhibitors are generally the drugs of first choice.

PMID- 9160215
TI  - Mood disorders in the female patient.
AB  - Disruptive changes in mood and low energy level are among the most common reasons
      women consult a physician. Usually no clear physiological explantation for these
      changes can be found. Many physicians feel uncomfortable dealing with patients
      with these complaints. The purpose of this paper is to discuss a practical
      approach to helping women with such conditions. A variety of terms have been
      utilized to refer to the situation in which a female patient has decreased energy
      or labile mood. Premenstrual Syndrome (PMS) and chronic fatigue syndrome (CFS)
      are currently popular terms. An association of low mood with menstrual cycle
      phase is undoubted, with the late luteal-early premenstrual phase most commonly
      associated with depression and irritability. It seems likely that women with PMS
      and those without it do not differ in circulating hormone levels during their
      cycles but rather in the brain response to these. Estrogen and progesterone
      receptors exist in the brain and change during the cycle. Elaborate diagnostic
      efforts are rarely rewarding in managing mood and energy disorders. Of more value
      is a careful history particularly concerned with the pattern of mood changes and
      with life stresses, accompanied by a thorough physical examination and laboratory
      tests. In most cases, changes in mood and energy are a variant of clinical
      depression. Changes in energy and sleep may be more evident than low affect.
      Treatment with an appropriate antidepressant, usually a selective serotonin re
      uptake inhibitor (SSRI), benefits most of these patients. Allowing the patient to
      express concerns about stressful life situations is often of great value.

PMID- 9160217
TI  - Hormone replacement therapy in the menopause.
AB  - The failure of follicular development that characterizes the menopause leads to a
      marked reduction in serum levels of estradiol and progesterone. As a result, the
      majority of women develop symptoms, including hot flushes, sleep disturbance, and
      vaginal dryness. Long-term consequences of ovarian insufficiency include genital
      atrophy, osteoporosis, and increased rates of myocardial infarction. Estradiol
      replacement (ERT) has proved effective in treating and preventing these problems.
      ERT has, however, led to increased risk of endometrial carcinoma. Consequently,
      treatment regimens now include progestins (HRT) to protect women who have a
      uterus. Progestins act by down-regulation of estradiol receptor activity, which
      is an advantage for preventing endometrial hyperstimulation, but a potential
      disadvantage when beneficial effects of estradiol are opposed. Current menopause
      health care includes assessment, treatment, and follow-up. Signs and symptoms of
      estradiol deficiency are evaluated during initial history-taking and physical
      examination. The MENSI (Menopause Symptom Index) has proved an efficient
      questionnaire for both initial assessment and monitoring of treatment effects.
      Vaginal cell maturation index (M.I.) can be helpful in determining need for
      hormonal treatment and for assessing response to treatment. A "therapeutic range"
      for ERT can be achieved with the availability of a variety of hormone
      preparations administered in different ways (oral, transdermal, skin gel,
      implants, etc.), thus avoiding the problems of both inadequate and excessive
      hormonal doses. This paper will describe a structured approach to the delivery of
      health care in the menopause.

PMID- 9160218
TI  - Evaluating health outcomes in a clinic environment.

PMID- 9160219
TI  - Palpitations: what is the mechanism, and when should we treat them?
AB  - Palpitation is an unpleasant awareness of an abnormal beating of the heart. This
      symptom may be brought on by a variety of cardiac disorders, such as
      cardiomyopathy, valvular heart disease, and coronary artery disease, but the most
      common cause is primary cardiac arrhythmias. Several noncardiac disorders may
      also cause palpitations, and in this case are an effect of the disease upon
      cardiac rhythm. Palpitations occur frequently in women at all ages, especially
      during the luteal phase of the menstrual cycle, during pregnancy, and during the
      perimenopausal period. Palpitations occurring at young age and associated with
      fast heart rate are frequently due to Wolff-Parkinson-White syndrome or other
      forms of re-entrant tachycardia, and may require catheter ablation. A correlation
      between ovarian hormones and occurrence of paroxysmal supraventricular
      tachycardia has recently been reported in female patients with normal menstrual
      cycles; palpitations are frequently reported in cases of mitral valve prolapse,
      whereas episodes of paroxysmal supraventricular tachycardia reported during
      pregnancy may be due to mechanical stimuli or to a suggested arrhythmogenic
      effect of pregnancy. Palpitations during the perimenopausal period are usually
      benign and seem to be related to the increased sympathetic activity caused by the
      menopause. Although the vast majority of palpitations are benign and need not be
      treated, an electrophysiological study is indicated for those patients who have a
      documented episode of palpitation associated with syncope or with a pulse that is
      inappropriately rapid during symptoms. The treatment of palpitations due to
      cardiac arrhythmias is dependent upon the kind of arrhythmia detected during
      either invasive or noninvasive electrophysiological studies.

PMID- 9160221
TI  - Diagnosis and treatment of viral STDs in women.
AB  - Viral sexually transmitted diseases (STDs) are a major health problem for women.
      Over many years the incidence of these infections has increased steadily to
      epidemic proportions. These infections not only cause short-term morbidity but
      also have been associated with significant long-term morbidity and mortality.
      This paper focuses on two of the most common viral STDs-Genital Herpes Simplex
      Virus (HSV) infection and Human Immunodeficiency Virus (HIV) infection of the
      female. The steady increase in the incidence of HIV infection and subsequent
      adult immunodeficiency disease (AIDS) among women requires health care providers
      to assume an active role in detection and treatment in order to avoid
      transmission, to protect the health of women with HIV/AIDS, and to reduce the
      risk of maternal-fetal (vertical) transmission. Because treatment with zidovudine
      has been shown to reduce vertical transmission, routine offering of HIV testing
      is currently recommended for all pregnant women. The approach to testing
      nonpregnant patients, i.e., the choice between selective screening or routine
      testing, rests with the individual clinician. Testing large numbers of patients
      within a practice may be facilitated by the availability of an oral antibody
      testing system. The sensitivity and specificity of the oral test is equivalent to
      blood testing. Serum and oral specimens are tested by enzyme-linked immunosorbent
      assays (ELISA) and confirmatory Western blot assays specifically designed for use
      with oral samples. Controversies in diagnosis as well as the most updated
      treatments for these infections are discussed.

PMID- 9160220
TI  - The brittle bone: how to save women from osteoporosis.
AB  - For a woman, the risk of suffering an osteoporotic fracture during her lifetime
      is higher than the combined risk of breast, endometrial, and ovarian cancer. It
      is important to reduce the number of osteoporosis-related fractures. Therefore,
      it is necessary to emphasize various interventions and attitudes which will
      decrease both the risk of falling and that of breaking bones. Strategies should
      be followed to reach adulthood with an optimal bone mass through improved diet
      and exercise during childhood. Programs that identify women with the lowest bone
      mass at the time of menopause may be useful, since prophylactic measures against
      osteoporosis such as hormone replacement therapy (HRT) can be offered to them.
      Identification of women at risk can be achieved through bone densitometry; a
      decrease of each standard deviation of bone mineral mass below mean values
      predicts a doubling of the fracture risk. Some data suggest that physicians are
      more willing to prescribe HRT specifically to women with the lowest bone mass,
      and that the latter are more likely to stay on therapy for longer periods of
      time. The decision to use HRT should be taken by the patient after proper
      information of all benefits (diminished climacteric symptoms, decrease of
      cardiovascular risk) and potential risks (possible enhanced breast cancer risk,
      appearance of side effect). In women who do not want to take HRT, or for whom
      contraindications exist, alternative medications, such as calcium, vitamin D and
      biphosphonates can be considered, depending on fracture risk. For older and
      institutionalized women, programs should be developed to decrease the risk of
      falling. Likewise, it may be possible to reduce the consequences of a fall, for
      instance by promoting the development of energy-absorbing hip pads, which reduce
      fracture risk.

PMID- 9160222
TI  - Predisposing factors to autoimmune disease.
AB  - There are many factors that predispose women to autoimmune disease. The
      protective effect of testosterone during development prevents most males from
      getting autoimmune disease, although in some instances this protective effect can
      be bypassed by either genetic anomalies or endocrinopathies. Autoimmunity is
      defined as the development of symptoms and antibodies referable to one or another
      autoimmune disease. Some of the factors that predispose young women to
      autoimmunity also directly involve the endocrine system and indirectly, disorders
      of gonadal development. Altered sex steroid metabolism is one endogenous factor
      that predisposes a young woman to autoimmunity. The metabolism of estrone which
      can be directed to either the 16-or the 2-metabolites by diet, thyroid function,
      or certain drugs has a major influence on immune function and possibly gonadal
      pathology. Attempts to shift the metabolism of estrone to the 2-compounds with a
      variety of agents actually decreases the predisposition to autoimmunity. Other
      pre-disposing factors are all related to hormone metabolism and include
      hyperprolactinemia, the use of exogenous estrogenic agents, or compounds that
      change basic steroid metabolism. Most of these conditions are reversible.

PMID- 9160223
TI  - Reappearance of the intrauterine device: a 'user-friendly' contraceptive.
AB  - Women in the United States, and their physicians, are "rediscovering"
      intrauterine devices (IUDs). Two IUDs, the 10-year Copper T 380A (Paragard) and 1
      year progesterone-releasing T (Progestasert) are currently marketed in this
      country. In contrast to previous perceptions, recent studies have provided
      reassurance regarding the safety of these effective and convenient
      contraceptives. We now recognize that IUDs do not increase salpingitis or
      infertility risks in long-term users. Likewise, we now better understand the
      mechanism of action of copper IUDs: both the inert plastic device as well as the
      copper contribute to a spermicidal effect, preventing fertilization. Finally, we
      now recognize that copper IUDs reduce a user's overall risk of ectopic pregnancy.
      For appropriately informed and selected candidates, IUDs represent a safe,
      effective, convenient, and low-cost contraceptive option.

PMID- 9160224
TI  - Prospective evaluation of the effect of biphasic waveform defibrillation on
      ventricular pacing thresholds.
AB  - INTRODUCTION: Significant increases in ventricular pacing threshold have been
      observed following monophasic waveform ventricular defibrillation shocks. High
      output pacing is recommended to ensure consistent capture, particularly in
      pacemaker-dependent patients who are likely to be defibrillated. Whether biphasic
      waveform defibrillation compounds this problem is not known. The purpose of this
      prospective study was to examine serial changes in ventricular pacing thresholds
      following single, multiple, low- and high-energy biphasic defibrillation shocks
      from an implanted defibrillator. METHODS AND RESULTS: Bipolar pacing thresholds
      before and after defibrillation, and the adequacy of pacing capture at three
      times preshock threshold in the immediate aftermath of ventricular
      defibrillation, were prospectively evaluated in 67 consecutively tested
      recipients of a biphasic implanted cardioverter defibrillator. Overall, serial
      pacing thresholds following successful defibrillation were completely unchanged
      after 141 of 177 (80%) ventricular fibrillation inductions. In no case did the
      threshold pulse width increment > 0.06 msec from its baseline value after shock,
      nor did pacing at a pulse width of three times preshock threshold from dedicated
      bipolar pacing electrodes fail to result in successful ventricular capture.
      Changes in threshold were not related to when measured from the time of shock,
      defibrillation energy, number of shocks, electrode system, chronicity of leads,
      shock orientation, or to clinical factors. CONCLUSIONS: No clinically important
      changes in pacing threshold were observed after biphasic waveform defibrillation.
      Bradycardia pacing at conventional pacemaker outputs of three times baseline
      pulse width threshold from bipolar electrodes dedicated exclusively to pacing or
      sensing (but not defibrillation) consistently allowed for an adequate safety
      margin following defibrillation.

PMID- 9160225
TI  - Effect of waveform tilt on defibrillation thresholds in humans.
AB  - INTRODUCTION: Despite the common use of the implantable cardioverter
      defibrillator to treat patients with life-threatening ventricular arrhythmias,
      the mechanism of defibrillation and the optimal waveform for implanted devices
      are poorly understood. All of the currently available pulse generators deliver
      exponentially declining pulses that are either automatically or manually
      truncated to achieve tilts of about 50% to 65%. Although this value was chosen
      based on experimental animal data, several theoretical models have been developed
      to describe defibrillation, which raise into question this choice of waveform
      shape. Accordingly, the present study was designed to test the effect of waveform
      tilt on defibrillation efficacy in humans. METHODS AND RESULTS: Twenty-three
      patients undergoing cardioverter defibrillator implantation were studied.
      Monophasic defibrillation thresholds (DFTs) were measured using a single reversal
      protocol at 35%, 50%, 65%, and 80% tilts by altering the pulse width of the
      shock. Mean defibrillation impedance was 41 +/- 6 omega. The DFT, measured by
      either leading-edge voltage or stored energy, was insensitive to altering the
      waveform tilt from 50% to 80%, only increasing when the tilt was reduced to 35%.
      A tilt of 65% yielded the lowest DFT voltage in only 8 of 23 patients.
      Significantly lower DFTs (> or = 40 V) were obtained using other tilts in seven
      patients. When the relationship between average current and pulse width was fit
      with a Weiss-Lapicque model, the data yielded a mean chronaxie of 4.6 +/- 3.0
      msec and a rheobase of 4.2 +/- 1.7 A, but considerable patient variability was
      observed. CONCLUSION: On average, DFTs in humans are insensitive to altering
      monophasic waveform tilts between 50% and 80%. There is, however, considerable
      patient variability, raising into question the premise that a single
      defibrillator waveform tilt is best for all patients.

PMID- 9160226
TI  - Electrophysiologic characteristics and radiofrequency catheter ablation in
      atrioventricular node reentrant tachycardia with second-degree atrioventricular
      block.
AB  - INTRODUCTION: Detailed electrophysiologic study of AV nodal reentrant tachycardia
      (AVNRT) with 2:1 AV block has been limited. METHODS AND RESULTS: Six hundred nine
      consecutive patients with AVNRT underwent electrophysiologic study and
      radiofrequency catheter ablation of the slow pathway. Twenty-six patients with
      2:1 AV block during AVNRT were designated as group I, and those without this
      particular finding were designated as group II. The major findings of the present
      study were: (1) group I patients had better anterograde and retrograde AV nodal
      function, shorter tachycardia cycle length (during tachycardia with 1:1
      conduction) (307 +/- 30 vs 360 +/- 58 msec, P < 0.001), and higher incidence of
      transient bundle branch block during tachycardia (18/26 vs 43/609, P < 0.001)
      than group II patients; (2) 21 (80.8%) group I patients had alternans of AA
      intervals during AVNRT with 2:1 AV block. Longer AH intervals (264 +/- 26 vs 253
      +/- 27 msec, P = 0.031) were associated with the blocked beats. However, similar
      HA intervals (51 +/- 12 vs 50 +/- 12 msec, P = 0.363) and similar HV intervals
      (53 +/- 11 vs 52 +/- 12, P = 0.834) were found in the blocked and conducted
      beats; (3) ventricular extrastimulation before or during the His-bundle
      refractory period bundle could convert 2:1 AV block to 1:1 AV conduction.
      CONCLUSIONS: Fast reentrant circuit, rather than underlying impaired conduction
      of the distal AV node or infranodal area, might account for second-degree AV
      block during AVNRT. Slow pathway ablation is safe and effective in patients who
      have AVNRT with 2:1 AV block.

PMID- 9160227
TI  - Transhepatic access to the atrioventricular ring for delivery of radiofrequency
      energy.
AB  - INTRODUCTION: Transcatheter radiofrequency ablation is an effective, safe
      treatment of arrhythmias in children. However, despite technical advances,
      patients with obstructed venous access to the heart have not been candidates for
      this treatment. METHODS AND RESULTS: Two children (8.2 and 10.9 kg) with complex
      congenital heart disease, supraventricular tachycardia, and obstructed venous
      access underwent successful radiofrequency ablation of either a right (one
      patient) or left (one patient) accessory pathway using the transhepatic route to
      the heart. CONCLUSION: This experience underscores the usefulness of the
      transhepatic approach in small patients, in patients with limited venous access,
      and in patients with complex congenital heart disease.

PMID- 9160228
TI  - Sawtooth first phase biphasic defibrillation waveform: a comparison with standard
      waveform in clinical devices.
AB  - INTRODUCTION: A major limitation in a conventional truncated exponential waveform
      is the rapid drop in current that results in short duration of high current or
      longer duration with a lower average current. We hypothesized that increasing the
      first phase average current by boosting the decaying waveform prior to phase
      reversal may improve defibrillation efficacy. METHODS AND RESULTS: To better
      simulate a "rectangular" waveform during the first phase, a "sawtooth"
      defibrillation waveform was constructed using "parallel-series" switching of
      capacitances (each 30 microF) during the first phase. This permitted a boost in
      the voltage late in the first phase. This sawtooth biphasic waveform (sawtooth)
      was compared to two clinical waveforms: a 135-microF capacitance (control-1) and
      a 90-microF capacitance (control-2) waveform. Defibrillation threshold (DFT)
      parameters were evaluated in 13 anesthetized pig models using a system consisting
      of a transvenous right ventricular apex lead (anode) and a left pectoral "hot
      can" electrode (cathode) system. DFT was determined by a "down-up down-up"
      protocol. The stored energy for sawtooth, control-1, and control-2 was 10.5 +/-
      2.8 J, 12.3 +/- 3.7 J*, and 12.2 +/- 2.8 J*, respectively (*P < or = 0.01 vs
      sawtooth). The average current of the first phase for sawtooth, control-1, and
      control-2 was 7.6 +/- 1.3 A, 4.7 +/- 0.9 A*, and 6.2 +/- 0.9 A*, respectively (*P
      = 0.0001 vs sawtooth). CONCLUSION: A sawtooth biphasic waveform utilizing a
      "parallel-series" switching system of smaller capacitors can improve
      defibrillation efficacy. A higher average current in the first phase generated by
      such a waveform may contribute to more efficient defibrillation by facilitating
      myocyte capture.

PMID- 9160229
TI  - Comparison of the rate-dependent properties of the class III antiarrhythmic
      agents azimilide (NE-10064) and E-4031: considerations on the mechanism of
      reverse rate-dependent action potential prolongation.
AB  - INTRODUCTION: Reverse rate-dependence, a lessening in Class III antiarrhythmic
      agent action potential duration (APD) prolongation as heart rate is increased,
      has been proposed to be related to an incomplete deactivation of the slow
      component (IKs) of the delayed rectifier K+ current (IK). The rate-dependent
      properties of block of IK by azimilide were compared to E-4031, which selectively
      blocks the rapid component (IKr) of IK, in guinea pig ventricular muscle. METHODS
      AND RESULTS: Azimilide prolonged APD in isolated papillary muscles in a
      concentration-dependent manner and to a greater degree than E-4031. Both agents
      prolonged APD less at fast than slow rates, consistent with a similar reverse
      rate-dependent effect. Isolation of azimilide block of IKs by subtraction of APD
      during E-4031 plus azimilide from E-4031 alone revealed rate-independent
      prolongation of APD. In voltage clamp experiments on single ventricular myocytes,
      activation of IKs was similar following 30 seconds of conditioning pulses of
      physiological duration (125 to 200 msec) with either a fast (cycle length 250
      msec) or slow (cycle length 2000 msec) rate. The block of IKs by azimilide 3
      microM was greater after a fast conditioning pulse train. CONCLUSIONS: Selective
      block of IKs prolongs APD in a rate-independent manner. In voltage clamped
      myocytes, no evidence of a rate-dependent accumulation of IKs was observed. These
      findings support a mechanism of reverse rate-dependent APD prolongation by Class
      III antiarrhythmic agents that block IKr independent of IKs.

PMID- 9160230
TI  - Simulated internal defibrillation in humans using an anatomically realistic three
      dimensional finite element model of the thorax.
AB  - INTRODUCTION: Determination of the optimal electrode configuration during
      implantable cardioverter defibrillator (ICD) implantation remains largely an
      empirical process. This study investigated the feasibility of using a finite
      element model of the thorax to predict clinical defibrillation metrics for
      internal defibrillation in humans. Computed defibrillation metrics from
      simulations of three common electrode configurations with a monophasic waveform
      were compared to pooled metrics for similar electrode and waveform configurations
      reported in humans. METHODS AND RESULTS: A three-dimensional finite element model
      was constructed from CT cross-sections of a human thorax. Myocardial current
      density distributions for three electrode configurations (epicardial patches,
      right ventricular [RV] coil/superior vena cava [SVC] coil, RV coil/SVC
      coil/subcutaneous patch) and a truncated monophasic pulse with a 65% tilt were
      simulated. Assuming an inexcitability threshold of 25 mA/cm2 (10 V/cm) and a 75%
      critical mass criterion for successful defibrillation, defibrillation metrics
      (interelectrode impedance, defibrillation threshold current, voltage, and energy)
      were calculated for each electrode simulation. Values of these metrics were
      within 1 SD of sample-size weighted means for the corresponding metrics
      determined for similar electrode configurations and waveforms reported in human
      clinical studies. Simulated myocardial current density distributions suggest that
      variations in current distribution and uniformity partially explain differences
      in defibrillation energy requirements between electrode configurations.
      CONCLUSION: Anatomically realistic three-dimensional finite element modeling can
      closely simulate internal defibrillation in humans. This may prove useful for
      characterizing patient-specific factors that influence clinically relevant
      properties of current density distributions and defibrillation energy
      requirements of various ICD electrode configurations.

PMID- 9160231
TI  - Regional gradation of L-type calcium currents in the feline heart with a healed
      myocardial infarct.
AB  - INTRODUCTION: Abnormal action potentials in myocytes adjacent to > 2-month-old
      feline LV myocardial infarcts (MI) may reflect alterations in Ca2+ currents
      (Ica). METHODS AND RESULTS: We compared ICa, at 36 degrees C, in subendocardial
      myocytes isolated from areas adjacent to MI and to ICa in cells from remote areas
      (> 4 mm away; REM) and control cells from similar regions in normal hearts.
      Control (CON) myocytes had membrane capacitance of 234 +/- 10 pF (n = 81 cells)
      compared to 305 +/- 14 pF in REM (71 cells; P < 0.05 from CON) and 237 +/- 11 pF
      (n = 55 cells) in MI (not different from CON). From Vh = -40 mV; peak ICa
      elicited by test potentials (-35 to +70 mV) were significantly larger in CON (
      1746 +/- 123 pA) and REM (-1795 +/- 142 pA) compared to MI (-1352 +/- 129 pA) (P
      < 0.05). Peak ICa density was significantly reduced in REM (-6.0 +/- 0.4 pA/pF)
      or MI (-5.7 +/- 0.4 pA/pF, P < 0.05) compared to CON (-7.5 +/- 0.4 pA/pF). Double
      exponential ICa decay was similar among groups. Half-inactivation potential
      (V0.5) was significantly shifted (hyperpolarizing direction) for MI (-29.1 +/-
      2.6 mV) and REM (-24.6 +/- 1.2 mV) myocytes compared to -20.3 +/- 1.0 mV in CON.
      MI slope factor (k; 9.0 +/- 0.5) was significantly different from CON (6.8 +/-
      0.3) and REM (7.3 +/- 0.4). No differences in time course of recovery from
      inactivation were noted. Five millimolar Ba2+o produced significant increases in
      ICa in CON and REM but an attenuated response in MI. Bay K8644 (1 microM)
      produced similar ICa increase in all groups. ICa increase due to isoproterenol (1
      microM) in MI and REM was half that in CON, but there were no differences in
      increased ICa responses among groups following phenylephrine (10 microM).
      CONCLUSION: Reduced ICa density in REM reflects cell hypertrophy, whereas altered
      ICa of MI may reflect altered channel structure and/or function.

PMID- 9160232
TI  - Paroxysmal atrioventricular block induced during head-up tilt testing in an
      apparently healthy man.
AB  - INTRODUCTION: Prolonged asystole during head-up tilt testing has been reported,
      but the occurrence of paroxysmal AV block appears to be rare. METHODS AND
      RESULTS: A 25-year-old man with no history of syncope underwent head-up tilt
      testing. After 11 minutes of 80 degrees tilting, he developed syncope with
      paroxysmal AV block and asystole lasting 10.5 seconds. However, this response was
      not reproduced during a subsequent tilt test 4 weeks later. Treadmill exercise
      testing and Holter monitoring showed no abnormalities. Power spectral analysis of
      heart rate variability revealed a marked increase in sympathetic activity several
      minutes before the induction of paroxysmal AV block. CONCLUSION: We report a case
      of paroxysmal AV block that occurred during head-up tilt testing but did not
      recur on a subsequent test in an apparently healthy young man.

PMID- 9160233
TI  - Successful radiofrequency catheter ablation of sustained ventricular tachycardia
      postmyocardial infarction in man guided by a multielectrode "basket" catheter.
AB  - Currently, analysis of sustained ventricular tachycardia postmyocardial
      infarction in man is limited by the time required for single point activation
      mapping and the difficulty in obtaining information during hemodynamically
      unstable arrhythmias. To overcome these limitations, we developed a
      multielectrode "basket" catheter for endocardial recording and pacing. This
      report describes the first clinical use of such a catheter to guide successful
      radiofrequency ablation of incessant sustained ventricular tachycardia
      postmyocardial infarction. This system may significantly shorten the time
      required for VT analysis and improve the results of radiofrequency catheter
      ablation for VT postmyocardial infarction.

PMID- 9160234
TI  - Mechanisms of idiopathic left ventricular tachycardia.
AB  - Idiopathic left ventricular tachycardia (ILVT) differs from idiopathic right
      ventricular outflow tract (RVOT) tachycardia with respect to mechanism and
      pharmacologic sensitivity. ILVT can be categorized into three subgroups. The most
      prevalent form, verapamil-sensitive intrafascicular tachycardia, originates in
      the region of left posterior fascicle of the left bundle. This tachycardia is
      adenosine insensitive, demonstrates entrainment, and is thought to be due to
      reentry. The tachycardia is most often ablated in the region of the
      posteroinferior interventricular septum. A second type of ILVT is a form
      analogous to adenosine-sensitive RVOT tachycardia. This tachycardia appears to
      originate from deep within the interventricular septum and exits from the left
      side of the septum. This form of VT also responds to verapamil and is thought to
      be due to cAMP-mediated triggered activity. A third form of ILVT is propranolol
      sensitive. It is neither or initiated or terminated by programmed stimulation,
      does not terminate with verapamil, and is transiently suppressed by adenosine,
      responses consistent with an automatic mechanism. Recognition of the
      heterogeneity of ILVT and its unique characteristics should facilitate
      appropriate diagnosis and therapy in this group of patients.

PMID- 9160235
TI  - Recent advances in cardiopulmonary resuscitation.
AB  - Mechanical and pharmacologic measures intended to increase blood flow to vital
      organs are the mainstay of therapy for patients in cardiac arrest. Several new
      cardiopulmonary resuscitation (CPR) techniques as well as novel devices and
      pharmacologic agents have been developed and tested since the first report of
      manual closed chested CPR over three decades ago. These recent mechanical and
      pharmacologic advances in the treatment of cardiac arrest are described. Some of
      these new techniques, devices, and drug therapies are presently undergoing
      clinical evaluation in patients in cardiac arrest. While many of these new
      methods and techniques have shown promise in small clinical trials in humans,
      none have yet to be found to be conclusively superior to manual closed chested
      CPR and treatment with standard pharmacologic agents.

PMID- 9160236
TI  - What is the mechanism of the wide QRS tachycardia?

PMID- 9160237
TI  - Prosodic abilities in children with specific language impairment.
AB  - The purpose of this study was to compare the receptive and expressive prosodic
      abilities of specifically language-impaired children to those of a matched group
      of control normal-language children. Each subject group consisted of ten 4-year
      olds, ten 5-year-olds and ten 6-year-olds. Subjects were administered two
      instruments which were designed for this purpose: the prosody imitation task and
      the emotion identification task. In the prosody imitation task subjects were
      required to imitate ten sentences with different linguistic and affective
      intonation contours. The emotion identification task required subjects to
      identify recordings of emotionally intoned sentences. Language-impaired children
      performed significantly less accurately on the imitation task but did not differ
      from normal-language children on the emotion identification task. Age was found
      to be a highly significant factor. On both tasks children performed better with
      increasing age. Results are discussed in reference to the developmental
      relationship between the child's learning of language and prosodic cues.

PMID- 9160238
TI  - A comparison of two phonological profiles: a tutorial.
AB  - The notion of "linguistic profile" as an alternative to standardized testing for
      speech and language disorders is discussed in this tutorial. Two specific
      examples of profiles, both for disordered phonology, are described, and readers
      are guided through their use. Finally, their relative strengths and weaknesses
      are assessed.

PMID- 9160239
TI  - Attitudes toward speech disorders: sampling the views of Cantonese-speaking
      Americans.
AB  - Speech-language pathologists who serve clients from cultural backgrounds that are
      not familiar to them may encounter culturally influenced attitudinal differences.
      A questionnaire with statements about 4 speech disorders (dysfluency, cleft
      pallet, speech of the deaf, and misarticulations) was given to a focus group of
      Chinese Americans and a comparison group of non-Chinese Americans. The focus
      group was much more likely to believe that persons with speech disorders could
      improve their own speech by "trying hard," was somewhat more likely to say that
      people who use deaf speech and people with cleft palates might be "emotionally
      disturbed," and generally more likely to view deaf speech as a limitation. The
      comparison group was more pessimistic about stuttering children's acceptance by
      their peers than was the focus group. The two subject groups agreed about other
      items, such as the likelihood that older children with articulation problems are
      "less intelligent" than their peers.

PMID- 9160240
TI  - The validity of reading comprehension therapy materials.
AB  - This study examines the degree to which reading comprehension therapy materials
      measure reading comprehension. Thirty-six non-brain-damaged adults (18 females,
      18 males) ranging in age from 55 to 75 years participated. They answered written
      multiple-choice questions from aphasia therapy workbooks before and after reading
      the paragraphs (n = 40) to which the questions related. Results showed that for
      each of four sets of workbook materials, subjects answered an average of 24% to
      49% more of the questions after reading the paragraphs relative to the number
      they answered before reading the paragraphs. For questions that could not be
      answered using one's prior knowledge, subjects were more dependent on having to
      read the paragraph in order to answer the questions correctly. Based on binomial
      probabilities, at least half of the questions from 32/40 paragraphs were answered
      correctly at greater than chance levels without reading the related paragraph.

PMID- 9160241
TI  - Calpains and calpastatin in SH-SY5Y neuroblastoma cells during retinoic acid
      induced differentiation and neurite outgrowth: comparison with the human brain
      calpain system.
AB  - Calpains have importance in human neurodegenerative disease pathogenesis, but
      these mechanisms are difficult to study in postmortem tissues. To establish a
      cellular model of the human calpain and calpastatin system, we characterized
      calpain I, calpain II, and calpastatin in SH-SY5Y human neuroblastoma cells in
      relation to their counterparts in human brain and investigated their expression
      and activity after inducing cellular differentiation with retinoic acid (RA), a
      physiological effector of normal brain development. Calpain I in both SH-SY5Y
      cells and human brain existed in the cytosolic and particulate fractions as three
      isoforms (80, 78, and 76 kDa) and exhibited atypical isoelectric focusing
      behavior. Calpain II in SH-SY5Y cells, as in human brain, migrated as a single
      predominantly cytosolic 76-kDa protein with an isoelectric point ranging from 5.9
      to 6.3. Calpastatin from both sources was also 90% cytosolic. In the cells it was
      composed of four discrete bands, ranging in molecular weight from 110 to 127 kDa.
      Levels of activated (76 and 78 kDa) and precursor (80 kDa) calpain I isoforms
      rose 54% (P < 0.0001) in the particulate fraction and 26% (P < 0.0001) in the
      soluble fraction after 3 days of RA exposure. Because levels and activity of
      calpastatin remain unchanged during the first 7 days of RA exposure, the
      increased abundance of calpain I implies a net activation of the calpain system
      during differentiation. Calpain I activation may contribute to the remodeling of
      cell shape and neurite extension/retraction associated with neuronal
      differentiation.

PMID- 9160242
TI  - Expression of chemokine genes in rat glial cells: the effect of myelin basic
      protein-reactive encephalitogenic T cells.
AB  - Chemokine gene expression and chemokine activity appear to be major components of
      the immunopathological processes of inflammation and autoimmunity. To initiate an
      investigation of the role of chemokines in the pathogenesis of autoimmune
      inflammatory demyelination, we examined the expression of mRNA transcripts
      encoding four prominent chemokines, IP-10, MIP-1 alpha, MCP-1, and RANTES, in
      encephalitogenic rat MBP-reactive T cells, astrocytes, and microglia. Astrocytes
      and microglia, whether as lines or as freshly isolated cells, did not
      constitutively express IP-10 and MCP-1 mRNA but could be induced with LPS to also
      produce MIP-1 alpha and RANTES. MBP-reactive T cells were induced with MBP to
      produce abundant levels of MIP-1 alpha, MCP-1, and RANTES mRNA in different
      temporal profiles but did not express IP-10 mRNA. In an MHC-II restricted
      fashion, the antigen-activated MBP-reactive T cells also induced glial cells to
      express all four chemokines, with the chemokine gene expression greatest
      following T-cell interactions with MHC-compatible glia. Treatment of glial cells
      with TNF-alpha and IFN-gamma induced only IP-10, indicating that the expression
      of chemokine genes other than IP-10 requires a combination of different cytokines
      or direct cell-cell contact between T cells and glia. Quantitative assays
      revealed that activated astrocytes, the dominant glia of the CNS, express higher
      levels of chemokine transcripts than transcripts of the major proinflammatory
      cytokines TNF-alpha and IFN-gamma. These results underscore the prominent but
      complex expression of chemokines by cellular component of inflammatory
      demyelinating lesions.

PMID- 9160243
TI  - Myelin proteolipid protein expressed in COS-1 cells is targeted to actin
      associated surfaces.
AB  - The compact myelin sheath represents one of the largest expanses of membrane
      membrane contact in the body and, in the central nervous system, requires the
      myelin proteolipid protein (PLP) for assembly. To determine whether the molecular
      properties of PLP promote membrane adhesion and direct its subcellular
      localization in the absence of oligodendrocyte-specific targeting mechanisms, PLP
      was expressed in COS-1 fibroblasts. Immunofluorescence staining indicated that
      PLP was translated effectively, transited the rough endoplasmic reticulum and
      Golgi apparatus, was delivered to the cell surface, and was endocytosed. In the
      plasma membrane, the PLP distribution was patchy and only sporadically coincided
      with sites of membrane-membrane contact between PLP-expressing cells. PLP was not
      randomly distributed, however, but correlated closely with microfilament
      locations in leading edge membranes and microvilli, as demonstrated by phalloidin
      double labeling. Our results indicate that even in non-myelinating cells, PLP can
      be concentrated in membranes associated with movement and growth, and suggest
      possible roles for the actin cytoskeleton in PLP localization. As PLP, DM20, and
      the DM20-like M6 protein all associate with actin-enriched membranes, this may be
      a common feature of PLP/DM20 gene family members.

PMID- 9160244
TI  - Early development of the oligodendrocyte in the embryonic chick metencephalon.
AB  - It has been demonstrated that the spinal cord oligodendrocytes in the vertebrates
      arise in the ventral ventricular zone adjacent to the floor plate in their early
      development. Because of the similarities of basic structures in the spinal cord
      and metencephalon, it is probable that the mode of early oligodendrocyte
      development in the metencephalon is the same as that in the spinal cord. We
      examined this possibility in chick embryos, using monoclonal antibodies O1 and
      O4, markers for oligodendrocyte lineage. An O4-positive (O4+) cell focus was
      observed in the medial ventricular zone of E5 chick ventral metencephalon (the
      earliest stage examined), adjacent to the floor plate. At E6, O4+ cells were
      dispersed from the medial to the lateral pons and, at E7, to the cerebellar
      anlagen. O4+ cells in the E6 brainstem and in the E7 cerebellum were unipolar in
      shape, whereas one day later, some of the labeled cells were multipolar with a
      few thin processes. O1+ oligodendrocytes first appeared at E8 in the ventromedial
      part of the pons and were distributed throughout the pons at E10 and in the
      cerebellum at E12. Explants from three subdivisions of the metencephalon (medial
      and lateral pons, and cerebellum) from E5 to E8 chick embryos were separately
      cultured to confirm the potential for generation of oligodendrocyte lineage. O4+
      cells appeared in the culture of the E5 medial pons (the earliest stage
      examined), in the E6 lateral pons, and in the E7 cerebellum. In addition, E7 was
      the youngest stage from which cerebellar explants were able to generate O1+
      oligodendrocytes. Our results clearly demonstrated the in vivo morphology of
      oligodendrocyte precursors in the metencephalon and their developmental
      appearance in a ventral-to-dorsal manner. From the bipolar morphology of O4+
      cells and the spacio-temporal continuity of the dispersion, it is inferred that
      the initial dispersion of O4+ cells may involve oligodendrocyte migration from
      the focus of the medial pons to the lateral and dorsal parts of the
      metencephalon.

PMID- 9160245
TI  - MPP+ induced apoptotic cell death in SH-SY5Y neuroblastoma cells: an electron
      microscope study.
AB  - PD is a common, late-onset neurodegenerative disorder that results in part from
      the gradual loss of dopaminergic neurons in the substantia nigra pars compacta.
      The neurotoxin MPTP can induce PD-like clinical symptomatology and
      neuropathological destruction and, thus, has been used as a PD model. The human
      neuroblastoma cell line SH-SY5Y possesses many of the qualities of human neurons
      and, as such, has served as a model for them. Apoptosis is the mode of cell death
      induced in SH-SY5Y cells by MPTP, and this was confirmed with nick end labeling
      and bisbenzimide staining. Transmission electron microscopic analysis of the
      ultrastructural changes occurring in neurotoxin exposed SH-SY5Ys revealed many
      morphological characteristics consistent with apoptosis. These changes included
      plasmalemmal blebbing, altered cytosolic density, nuclear condensation and
      fragmentation, pronounced vacuole formation, ribosomal dispersion, and the
      disappearance of the golgi complex, microtubules, and smooth endoplasmic
      reticulum. Limited amounts of rough endoplasmic reticulum and mitochondria
      exhibited normal morphology throughout the apoptotic changes but then were
      disrupted during secondary necrotic changes. The in vitro induction of apoptosis
      by a parkinsonism neurotoxin might be reflective of the mechanisms of in vivo
      nigral degeneration occurring during PD.

PMID- 9160247
TI  - Met5-enkephalin-Arg6-Phe7, an endogenous neuropeptide, binds to multiple opioid
      and nonopioid sites in rat brain.
AB  - Receptor binding properties of the naturally occurring opioid heptapeptide MERF
      were studied in rat brain membrane preparations using tritium-labeled derivative
      of the peptide with 40 Ci/mmol specific radioactivity. Binding assays were
      performed in the presence of broad-spectrum peptidase inhibitors at 0 degree C.
      Under these conditions, the equilibrium binding was achieved in 30-40 min, and
      approximately 90% of the applied radioligand remained unchanged as determined by
      HPLC analysis. The apparent affinity (Kd value) of [3H]Met-enkephalin-Arg6-Phe7,
      calculated from saturation binding data, was 10.2 +/- 2.5 nM, and the maximal
      number (Bmax) of the heptapeptide binding sites was found to be 468 +/- 43
      fmol/mg protein. About half the sites represent nonopioid sites because the Bmax
      was only 255 +/- 30 fmol/mg, when the nonspecific binding was measured with 1
      microM naloxone. The rank order potencies of the examined compounds revealed that
      the opioid component of [3H]Met-enkephalin-Arg6-Phe7 recognition site are
      probably not mu and certainly not kappa 1 sites, whereas these sites are
      characterized by a kappa 2-like binding profile. Considering the discrepancies
      between rat and frog brain found in the affinity of some compounds, including
      naltrindole and norbinaltorphimine, the presence of a novel, MERF-selective
      "heptapeptide" binding site in rat brain membranes is also suggested. A number of
      the heterologous competition curves could be described by a high-affinity
      stereospecific component and a substantially lower-affinity binding element,
      which could completely be displaced with several peptide ligands such as Met5
      enkephalin, dynorphin(1-13), and unlabeled MERF but not by other compounds such
      as [D-Ala2-(Me)Phe4-Gly5-ol]enkephalin, morphine, or naloxone. [3H]Met-enkephalin
      Arg6-Phe7 binding can also be inhibited by FMRF-amide analogs and sigma receptor
      ligands, such as (+)N-allyl-normetazocine and haloperidol, although with moderate
      affinity. It is concluded that the stereospecific high-affinity binding is of
      opioid in character, whereas the residual sites characterized with their lower
      affinity are naloxone-insensitive nonopioid sites.

PMID- 9160246
TI  - Dopamine enhances somatostatin receptor-mediated inhibition of adenylate cyclase
      in rat striatum and hippocampus.
AB  - Although there is evidence that suggests that dopamine (DA) has stimulatory
      effects on somatostatinergic transmission, it is unknown to date if DA increases
      the activity of the somatostatin (SS) receptor-effector system in the rat brain.
      In this study, we evaluated the effects of the administration of DA and the DA D1
      like (D1, D5) receptor antagonist SCH 23390 and the D2-like (D2, D3, D4) receptor
      antagonist spiperone on the SS receptor-adenylate cyclase (AC) system in the
      Sprague-Dawley rat striatum and hippocampus. An intracerebroventricular injection
      of DA (0.5 microgram/rat) increased the number of SS receptors and decreased
      their apparent affinity in the striatum and hippocampus 15 hr after its
      administration. The simultaneous administration of the DA receptor antagonists
      SCH 23390 (0.25 mg/kg, ip) and spiperone (0.1 mg/kg, ip) before DA injection
      partially prevented the DA-induced increase in SS binding. The administration of
      SCH 23390 plus spiperone alone produced a significant decrease in the number of
      SS receptors in both brain areas studied at 15 hr after injection, an effect that
      disappeared at 24 hr. The increased number of SS receptors in the DA-treated rats
      was associated with an increased capacity of SS to inhibit basal and forskolin
      (FK)-stimulated (AC) activity in the striatum and hippocampus at 15 hr after
      injection. This effect had disappeared at 24 hr. By contrast, basal and FK
      stimulated enzyme activities were unaltered after DA injection. No significant
      changes in the levels of the alpha i (alpha i1 + alpha i2) subunits were found in
      DA-treated rats as compared with control rats. In addition, the immunodetection
      of the alpha i1 or alpha i2 subunits showed no significant changes in their
      levels in DA-treated rats when compared with controls. DA injection also induced
      an increase in SS-like immunoreactive content in the rat striatum but not
      hippocampus at 15 hr after administration and returned to control values at 24
      hr. These results provide direct evidence of a functional linkage between the
      dopaminergic and somatostatinergic systems at the molecular level.

PMID- 9160248
TI  - Specific proteolytic cleavage of the myristoylated alanine-rich C kinase
      substrate between Asn 147 and Glu 148 also occurs in brain.
AB  - The myristoylated alanine-rich C kinase substrate (MARCKS) is a major ubiquitous
      substrate of protein kinase C. The expression of the protein is regulated during
      cell cycle progression and cell proliferation. Specific proteolytic cleavage of
      the protein between Asn 147 and Glu 148 was described recently in cultured cells,
      and the corresponding proteolytic activity was observed in various tissue
      extracts except for brain. We purified a 40 kDa fragment of MARCKS from bovine
      brain that we characterized as the C-terminal specific fragment found in other
      tissues. The identification of the fragment was achieved by in vitro
      phosphorylation by protein kinase C, calcium-dependent interaction with
      calmodulin, mass spectrometric analysis, and N-terminal sequencing. These data
      suggest that specific proteolytic cleavage of MARCKS also occurs in brain and may
      be a general mechanism of down-regulation of the protein.

PMID- 9160249
TI  - Replenishment of docosahexaenoic acid in n-3 fatty acid-deficient fetal rats by
      intraamniotic ethyl-docosahexaenoate administration.
AB  - A procedure for intraamniotic ethyl-docosahexaenoate (Et-DHA) administration was
      used to restore the docosahexaenoic acid (DHA; 22:6 n-3) levels in n-3-deficient
      fetal rats. The state of deficiency, characterized by a 34% and 60% decrease in
      DHA content of fetal brain and liver, respectively, was attained by feeding the
      pregnant dams from day 8 and up to 20 days gestation, with an n-3 linolenic acid
      deprived diet. After a single intraamniotic administration of Et-DHA on day 18 or
      19, a rapid increase in both fetal brain and liver DHA was achieved. This
      increase was accompanied by a decrease in the docosapentaenoic acid (DPA; 22:5 n
      6) level. After 48 hr following Et-DHA administration, the major phospholipids
      (PLs) phosphatidylserine (PS), phosphatidylethanolamine (PE), and
      phosphatidylcholine (PC), together accounting for more than 90% of total lipid
      phosphorus in sunflower oil (SFO)-treated animals, regained the DHA content to
      levels similar to control animals in both fetal brain and liver tissues. Unlike
      brain, however, most of the DHA content in liver PLs was restored by 24 hr,
      suggesting that the fetal liver may have a higher metabolic turnover. The DHA/DPA
      ratio was used to assess the degree of DHA correction. Fetal brain PS, PC, and PE
      ratios following Et-DHA administration grew steadily over a period of 48 hr but
      reached only approximately 60% of the control levels. Liver PS regained a value
      similar to the control, while those of PC and PE were 33% and 46% lower than the
      controls, respectively. Alterations in the PL polar head-group composition were
      observed following the dietary manipulations and Et-DHA administration. Although
      the intraamniotic injection is an invasive approach, the ability to rapidly
      enhance DHA acylation during intrauterine life may hold potential clinical value
      whenever an indication for DHA deficiency exists.

PMID- 9160250
TI  - Ethanol alters the concentration of Met-enkephalin in brain by affecting peptide
      transport system-1 independent of preproenkephalin mRNA.
AB  - Alcohol-related events have been proposed to be under neurochemical control. For
      example, the concentration of methionine enkephalin (Met-enkephalin) in brain has
      been inversely correlated with ethanol consumption in alcohol-preferring and
      alcohol-nonpreferring mice. The concentrations of Met-enkephalin are controlled
      in part by peptide transport system-1 (PTS-1), a brain-to-blood transport system
      for Met-enkephalin located at the blood-brain barrier. We examined the
      relationships among concentrations of Met-enkephalin, preproenkephalin (PPE)
      mRNA, and PTS-1 activity in mice exposed to ethanol. PTS-1 activity decreased
      progressively during the process of addiction and then partially recovered within
      hours after withdrawal of ethanol. Serotonin lost its ability to modulate PTS-1
      activity in exposed mice, indicating that regulation of PTS-1 activity was
      affected by ethanol. Concentrations of Met-enkephalin tended to move in the
      opposite direction from PTS-1 activity, increasing significantly with addiction.
      In naive mice, PPE mRNA levels correlated with the concentrations of Met
      enkephalin. However, levels of PPE mRNA remained unchanged during addiction,
      withdrawal, and recovery, no longer correlating with concentrations of Met
      enkephalin. These results suggest that ethanol affects concentrations of Met
      enkephalin in brain through post-transcriptional mechanisms and that PTS-1
      activity is one of those mechanisms.

PMID- 9160251
TI  - Prevention of motoneuron death by adenovirus-mediated neurotrophic factors.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      characterized by progressive loss of motoneurons, and has no effective treatment.
      Experimental studies in rodents have shown that motoneurons respond to a variety
      of molecules including brain-derived neurotrophic factor (BDNF). and the glial
      cell line-derived neurotrophic factor (GDNF). Here we investigated the
      neuroprotective effect of these growth factors, encoded by an adenovirus, on the
      death of axotomized facial motoneurons in newborn rats. We used a new gene
      therapy strategy that involves gene transfer to motoneurons by intramuscular
      injection of an adenoviral vector, which is retrogradely transported from
      injected target muscle (Finiels et al.,: NeuroReport 7:373-378, 1995). A
      significant increased survival of motoneurons was observed in animals pretreated
      with adenovirus encoding BDNF (34.5%, P < 0.05) ou GDNF (41.9%, P < 0.05) 1 week
      after axotomy. These results indicate that pretreatment with BDNF or GDNF, using
      this therapeutic strategy, is able to prevent the massive death of motoneurons
      that normally follows axotomy in the neonatal period, opening new perspectives to
      limit neuronal death in degenerative disorders.

PMID- 9160252
TI  - Qualitative and quantitative measurements of oligonucleotides in gene therapy:
      Part I. In vitro models.
AB  - Part I of this review attempts to bring together all the methods of detection and
      determination of synthetic oligonucleotides used in in vitro, described in the
      literature over the past 14 years, in an effort by scientists to use these
      oligonucleotides as drugs in gene therapy. The in vitro models include cell-free
      and cell culture systems. Emphasis has been given to the techniques developed for
      quantification of the input oligonucleotides or their metabolites. The purpose of
      study, methods of processing, detection and determination techniques such as
      those based on fluorescence, radiolabeling, high-performance liquid
      chromatography, gel-electrophoresis and others have been presented.

PMID- 9160253
TI  - Extraction of pharmaceuticals using pressurised carbon dioxide.
AB  - This paper reviews the applications of super- and sub-critical carbon dioxide for
      the extraction of pharmaceuticals from various matrices. The matrices covered are
      divided into the following types: animal feed, formulations, biological and
      miscellaneous, with various sub-divisions as appropriate. The polar nature of
      most pharmaceuticals often precludes the use of carbon dioxide only, so it is
      common to find the addition of a more polar solvent, as modifier. As the majority
      of sample types covered are solid, little if any pre-treatment is required, with
      the exception of grinding, prior to insertion in the sample extraction cell. For
      liquid-type matrices, sample pre-treatment is the normal. Often this may involve
      adsorption on an inert support e.g. Celite or diatomaceous earth, or
      immobilisation on a functionalised silica surface, e.g. C18. The later may take
      the form of a solid phase extraction cartridge or disk. An attempt has also been
      made to sample from liquid matrices directly using a modified extraction cell.
      The variety of sample types, matrices and analyte polarity places stringent
      requirements on the use of pressurised carbon dioxide. Its potential for
      effective recovery is examined in this review.

PMID- 9160254
TI  - Structure elucidation of a photodegradation product of ciprofloxacin.
AB  - In the photochemical degradation of ciprofloxacin, 1-cyclopropyl-6-fluoro-1,4
      dihydro-4-oxo-7-(piperazinyl)-3-quinolone carboxylic acid, two major
      decomposition products are formed in acidic solution. The main degradation
      product, after both artificial and daylight exposure, was 7-amino-1-cyclopropyl-6
      fluoro-1,4-dihydro-4-oxo-3-quinolone carboxylic acid. This product was also the
      dominating compound after more than 5 h irradiation with a high-pressure mercury
      lamp in aqueous solutions at pH < or = 2 when the solvent additionally contained
      water-miscible organic solvent. The structure of the isolated compound was
      elucidated on the basis of the chemical behaviour in thin-layer and high
      performance liquid chromatography, and of information from infrared, ultraviolet,
      mass and nuclear magnetic resonance spectra.

PMID- 9160255
TI  - Determination of moisture in hard gelatin capsules using near-infrared
      spectroscopy: applications to at-line process control of pharmaceutics.
AB  - A method is proposed in which diffuse reflectance near-infrared spectroscopy
      (NIR) is applied in an at-line process analytical interface to determine moisture
      content in bulk hard gelatin capsules. Capsule samples were equilibrated at
      various relative humidities and the moisture contents were determined using loss
      on drying (LOD). Different multivariate calibration methods using multiple linear
      regression (MLR) and partial least squares regression (PLSR) and various spectral
      pretreatments were compared. No sample pretreatment was required and the analysis
      time was 1-2 min. The investigated range for the moisture determination was 5.6
      18.0% w/w and the root mean square error of prediction (RMSEP) value was 0.1%
      w/w.

PMID- 9160256
TI  - NMR and HPLC-NMR spectroscopic studies of futile deacetylation in paracetamol
      metabolites in rat and man.
AB  - HPLC-NMR spectroscopy has been used to investigate the level of deacetylation
      followed by reacetylation (futile deacetylation) of metabolites of paracetamol
      detected in human and rat urine. This has been achieved through the synthesis and
      administration of paracetamol isotopically labeled at the acetyl group with C2H3,
      13CH3 and 13CO-13CH3. Using paracetamol-C2H3 it had been shown that in the rat
      the sulphate metabolite present in the urine shows 10-13% futile deacetylation
      depending on the dose, whereas for paracetamol-13CO-13CH3 the corresponding value
      was about 8%. After solid phase extraction, it was also possible to determine the
      level of futile deacetylation in the glucuronide metabolite using directly
      coupled HPLC-NMR. This approach was facilitated by the use of acetonitrile-d3 as
      an HPLC eluent and the HPLC-NMR analyses showed that the level of futile
      deacetylation in the sulphate and glucuronide metabolites were equal at about 9%.
      The glucuronide of paracetamol-C2H3 was the predominant metabolite in man and
      following separation using HPLC-NMR, the level of futile deacetylation was shown
      to be 1% for the glucuronide and 2% for the sulphate, these values being equal
      within experimental error. This work demonstrates the utility of NMR and HPLC-NMR
      spectroscopy for isotope exchange studies.

PMID- 9160257
TI  - Spectrophotometric determination of methoxamine using cerium(IV) in presence of
      sodium lauryl sulphate and rhodamine-B.
AB  - A sensitive spectrophotometric assay has been developed for the determination of
      methoxamine in pure dosage form and in its pharmaceutical preparations. The
      method is based on the acidic oxidation of methoxamine with cerium(IV) in the
      micellar medium of sodium lauryl sulphate at 96 degrees C. The reaction yields a
      water-soluble purple product which can be quantified spectrophotometrically at
      505 nm. The calibration curve was linear between 1.0 and 20 micrograms ml-1 with
      a limit of detection 0.5 microgram ml-1. The molar absorptivity at 505 nm is 8.3
      X 10(3) iota mol-1 cm-1. The method is simple and rapid since the product is
      measured directly in solution without extraction.

PMID- 9160258
TI  - Radioimmunoassay for the measurement of S9788 in serum and microdialysis samples.
AB  - S9788, 6-[4-(2,2-di-(fluorophenyl)-ethylaminol-1-piperdinyl]-N,N'-d i-2-propenyl
      1, 3,5-triazine- 2, 4-diamine, is a novel compound designed to reverse tumour
      multidrug resistance associated with cancer chemotherapy. A specific and
      sensitive radioimmunoassay has been developed for the analysis of S9788 in serum
      samples and adapted for samples obtained by microdialysis. The limit of
      quantitation is 0.2 ng ml-1 in perfusion medium and there is no cross reactivity
      of the antibody with known metabolites of the parent compound or with certain
      cytotoxic compounds likely to be coadministered with S9788. Maximum probe
      recovery during microdialysis was 66% at a flow of 1 microliter min-1, using
      Ringer/BSA (70 mg ml-1) as the perfusion medium. The assay has sufficient
      sensitivity, precision, accuracy and specificity for the analysis of rat and
      human serum and microdialysis perfusate samples. The assay has been successfully
      applied to the determination of S9788 in rat plasma (total concentration) and the
      microdialysate of the same samples.

PMID- 9160259
TI  - Identification of drugs in pharmaceutical dosage forms by X-ray powder
      diffractometry.
AB  - A simple X-ray powder diffractometric (XRD) method was developed for the
      identification of the active ingredient in a variety of dosage forms. The method
      was successfully used to unambiguously identify the active ingredient(s) in
      tablet, capsule, suppository and ointment formulations. The unique feature of the
      method is that it provides information about the solid-state of the drug. Thus, a
      capsule formulation containing anhydrous ampicillin was readily distinguished
      from that containing ampicillin trihydrate. The USP stipulates the use of the
      beta-polymorphic form of anhydrous carbamazepine in carbamazepine tablets.
      Contamination by the alpha-polymorph (down to a level of 1.4% w/w of the
      formulation) could be detected. In some of the multicomponent formulations, there
      was a pronounced overlap of the powder patterns of ingredients which made
      identification difficult. This problem was solved by using a pattern subtraction
      technique, which permitted selective subtraction of the XRD pattern of the
      constituents of the formulation from the overall XRD pattern. Such an approach
      enabled identification of the drug even when it constituted only 5% w/w of the
      formulation. The method also permitted simultaneous identification of the
      multiple active ingredients in trimethoprim-sulfamethoxazole and acetaminophen
      aspirin-caffeine formulations.

PMID- 9160260
TI  - Selective fluorogenic derivatization of a peptide nucleic acid trimer with
      naphthalene-2,3-dicarboxaldehyde.
AB  - The reversed-phase high-performance liquid chromatography of a Peptide Nucleic
      Acid (PNA) trimer has been studied after its preseparation fluorogenic
      derivatization with naphthalene-2,3-dicarboxaldehyde in the presence of cyanide
      (NDA/CN). Trace levels of the PNA trimer were determined in cell homogenate
      samples containing the PNA trimer at prederivatization concentrations as low as
      48.9 ng ml-1. The sample pretreatment operations included a deproteination step,
      achieved by ultra-filtration, followed by fluorogenic derivatization (NDA/CN).
      Subsequently, to achieve adequate selectivity, the fluorescently labeled PNA was
      subjected to high performance anion exchange chromatography prior to quantitation
      via fluorescence detection. The various problems encountered during sample
      pretreatment and separation of derivatized PNA trimer in biological samples are
      presented and discussed.

PMID- 9160261
TI  - The new inhibitors of ribonucleotide reductase--comparison of some physico
      chemical properties.
AB  - Amidox (AX), didox (DX) and trimidox (TX), compounds synthetized as new
      ribonucleotide reductase inhibitors, have been investigated by ultraviolet (UV)
      spectrophotometry, polarography and high performance liquid chromatography
      (HPLC). The experiments have been performed at various pH values. The changes in
      UV absorption of the compounds studied were recorded and it was demonstrated that
      these changes are related to the pH and to structural features of the
      investigated molecules. From the compounds included in our series of experiments,
      only amidox and trimidox are reduced during polarographic experiments in Britton
      Robinson buffer. The reduction of both compounds proceeded in two one-electron
      steps in acidic pH. One two-electron diffuse irreversible wave was observed at
      basic pH. The values of the half-wave potential became more negative in
      accordance with the increasing pH. HPLC assay also showed changes in the
      retention of compounds investigated, particularly when the pH of the mobile phase
      was close to the dissociation constant of the particular drug. The changes of
      physico-chemical properties detected by the all used methods are related to
      different chemical structures (the most significant changes were observed in
      alkaline pH).

PMID- 9160262
TI  - Whole blood cyclosporin monitoring in liver and heart transplant patients:
      evaluation of the specificity of a fluorescence polarization immunoassay and an
      enzyme-multiplied immunoassay technique.
AB  - The specificity of two cyclosporin immunoassays were evaluated. Eleven patients
      were followed for the first four weeks after heart (n = 3) or liver (n = 8)
      transplantation. Cyclosporin A (CsA) monitoring was performed concomitantly by a
      monoclonal fluorescence polarization immunoassay (mFPIA) and enzyme-multiplied
      immunoassay technique (EMIT) during this period. For several patients,
      cyclosporin monitoring was also performed by high performance liquid
      chromatography (HPLC) or by polyclonal fluorescence polarization immunoassay
      (pFPIA). Liver function was assessed by follow-up of plasma total bilirubin,
      gamma-glutamyl transferase and alkaline phosphatase and renal function by plasma
      creatinine. All the patients presented episodes of impaired liver function.
      Higher CsA levels were found using mFPIA measurements as compared to the EMIT
      measurements (ratio mFPIA:EMIT (medium range) = 1.4 (1.0-2.3)). A higher degree
      of cross-reactivity of the antibody used in the mFPIA as compared to the EMIT was
      demonstrated by specific measurements of CsA and its primary metabolite, AM1, by
      HPLC.

PMID- 9160263
TI  - The determination of a degradation product in clidinium bromide drug substance by
      capillary electrophoresis with indirect UV detection.
AB  - A capillary electrophoresis (CE) method utilizing indirect ultraviolet (UV)
      detection was developed for the determination of a non-UV absorbing degradation
      product, Ro 5-5172, in clidinium bromide drug substance. The electrophoresis
      buffer consisted of sodium phosphate and benzyltrimethylammonium bromide. Rinsing
      the capillary with sodium hydroxide followed by water then fresh capillary
      electrophoresis buffer was found to significantly improve the reproducibility of
      the migration times of the analytes. To further improve run-to-run
      reproducibility, an internal marker was used to account for differences in
      injection volumes and migration times between runs. The precision of the method
      was found to be less than 1% relative standard deviation for the migration time
      ratio and peak area ratio of Ro 5-5172 to the internal standard. The method was
      found to be linear for 0.05-1% Ro 5-5172 with respect to a 10 mg ml-1 sample
      preparation. The limit of detection was found to be less than 0.01% Ro 5-5172.
      Results obtained for the analysis of a clidinium bromide drug substance lot using
      this CE method and a thin layer chromatography method were compared and found to
      be in agreement.

PMID- 9160264
TI  - Mangafodipir trisodium injection, a new contrast medium for magnetic resonance
      imaging: detection and quantitation of the parent compound MnDPDP and metabolites
      in human plasma by high performance liquid chromatography.
AB  - Manganese(II) dipyridoxyl diphosphate (MnDPDP) is the active component of
      mangafodipir trisodium injection (Teslascan), a new contrast medium for magnetic
      resonance imaging. A high performance liquid chromatography (HPLC) method was
      developed for the simultaneous determination of MnDPDP and its five major
      metabolites in human plasma, i.e. the dephosphorylation products MnDPMP
      (manganese(II) dipyridoxyl monophosphate) and MnPLED (manganese(II) dipyridoxyl
      ethylenediamine diacetate) and the corresponding substances obtained after
      transmetallation with zinc (ZnDPDP, ZnDPMP and ZnPLED). Heparinized blood samples
      from patients receiving mangafodipir trisodium injection were immediately mixed
      with solid trisodium phosphate dodecahydrate to obtain pH 10.0 +/- 0.2 in order
      to inhibit further in vitro dephosphorylation and transmetallation. The plasma
      thus obtained was ultrafiltrated prior to HPLC analysis. The chromatographic
      separation was obtained using a mixed-bed resin with both anion exchange and
      reversed-phase functions (OmniPac PAX-500) using isocratic elution and UV
      detection at 310 nm. With an injection volume of 50 microliters, the limit of
      quantitation (LOQ) values were 0.8-2.3 microM for the Mn compounds and 0.1-0.8
      microM for the Zn compounds. The between-run accuracy of spiked plasma samples
      was in the range 97.5-106.7% with a precision in the range 3.1-9.0%. The best fit
      calibration curves were obtained using non-linear regression according to the
      equation Y = A + BXM in the concentration range from LOQ to 100 microM. Long-term
      storage of spiked plasma samples for three months at -20 degrees C demonstrated
      the required stability with recovery values within 85-115% of MnDPDP and its five
      metabolites.

PMID- 9160265
TI  - Mangafodipir trisodium injection, a new contrast medium for magnetic resonance
      imaging: in vitro metabolism and protein binding studies of the active component
      MnDPDP in human blood.
AB  - The binding to human serum proteins of MnDPDP (manganese(II) dipyridoxyl
      diphosphate), the active component of the magnetic resonance imaging contrast
      medium mangafodipir trisodium injection (Teslascan) was studied in
      ultrafiltration experiments. Sera from three males and three females were
      incubated with 86 microM [14C]MnDPDP for 60 min at room temperature (20-23
      degrees C), followed by centrifugation through filters with a cut-off of 30 kDa.
      Analysis of the filtrates and the initial incubation mixtures for manganese, by
      ICP-AES, and for DPDP and its dephosphorylated metabolites DPMP (dipyridoxyl
      monophosphate) and PLED (dipyridoxyl ethylenediamine diacetate) by liquid
      scintillation counting, showed a clear difference in protein binding of manganese
      and the ligands under these conditions. Only 2.2 +/- 1.8% (mean +/- S.E.; n = 6)
      of DPDP, DPMP and PLED were bound to protein, whereas 26.9 +/- 2.9% (mean +/-
      S.E.; n = 6) of manganese was bound to protein. No binding of DPDP, DPMP or PLED
      to blood cells was observed when whole blood, containing either heparin or EDTA
      as anticoagulant, was spiked with [14C]MnDPDP and the cell-free fraction and the
      lysed cell fraction analysed by liquid scintillation counting. The extent of
      protein binding of manganese corresponded well with results from an in vitro
      metabolism study, in which MnDPDP was added to heparinized human whole blood,
      showing that approximately 25% of DPDP, DPMP or PLED were not bound to manganese.
      The in vitro metabolism study revealed that transmetallation with zinc was nearly
      complete within 1 min, and that dephosphorylation is a sequential process going
      from DPDP to the monophosphate DPMP, and then to the fully dephosphorylated
      compound PLED.

PMID- 9160266
TI  - Development and validation of a liquid chromatographic method for the
      determination of related substances in verapamil hydrochloride.
AB  - The development of a reversed-phase liquid chromatographic method for the
      determination of related substances in verapamil hydrochloride is described. The
      method is based on the use of a simple mobile phase on a specialty base
      deactivated reversed-phase column. It enables the resolution of 13 related
      compounds from the parent drug and from each other. Validation of the method
      showed it to be reproducible, selective, accurate and linear over the
      concentration range of analysis with a limit of detection of 0.5 microgram ml-1.
      The developed method proved to be a real improvement compared with the LC test
      for chromatographic purity described in the USP monograph for verapamil
      hydrochloride.

PMID- 9160267
TI  - High-performance liquid chromatographic assay of dilazep in plasma after solid
      phase extraction.
AB  - A new, simple and accurate high-performance liquid chromatography method is
      presented for measuring dilazep in plasma, using a reversed-phase technique and
      UV absorption at 267 nm. Dilazep and papaverine (the internal standard) added to
      plasma were successfully isolated using a solid-phase extraction procedure (CN
      cartridges). The method was linear between 2.5-12.5 micrograms ml-1. Over the
      tested concentration range the intra-day coefficient of variation for replicate
      analyses of plasma ranged from 2.38 to 5.27% (the day-to-day CV ranged from 2.52
      to 7.99%). The detection limit for the analysis of dilazep in plasma was 50 ng
      with 20 microliters injection.

PMID- 9160268
TI  - Low level determination of dorzolamide and its de-ethylated metabolite in human
      plasma by liquid chromatography with atmospheric pressure chemical ionization
      tandem mass spectrometry.
AB  - A sensitive and specific method for the determination of dorzolamide (I) and its
      de-ethylated metabolite (II) in human plasma has been developed utilizing high
      pressure liquid chromatography (HPLC) with tandem mass spectrometric (MS/MS)
      detection. The analytes and internal standard (III) were isolated from the
      deproteinized pH 8.0 buffered plasma, using a liquid-liquid extraction with a
      mixture of ethyl acetate, toluene, and isopropanol. The analytes were then back
      extracted into 0.085% phosphoric acid (200 microliters) and after washing the
      acidic extract with hexane, the organic layer was discarded and a fraction (50
      microliters) of the acid extract was injected into the LC/MS/MS system. The MS/MS
      detection was performed on a PE Sciex API III tandem mass spectrometer using a
      heated nebulizer interface. Multiple reaction monitoring of the parent-->product
      ion combinations of m/z 325-->199, 297-->199, and 397-->306 were used to quantify
      I, II, and III, respectively. The assay was validated in the concentration ranges
      of 0.5-100 and 2.5-100 ng ml-1 of plasma for I and II, respectively. The
      precision of the assays, expressed as coefficients of variation (C.V.%), were
      less than 10% over the entire concentration range, with adequate assay
      specificity and accuracy. The LC/MS/MS method provided a 10-fold increase in the
      sensitivity of I over the previously reported HPLC/UV method [1].

PMID- 9160269
TI  - A method using a liquid chromatographic-electrospray-mass spectrometric assay for
      the determination of antimigraine compounds: preliminary pharmacokinetics of MDL
      74,721, sumatriptan and naratriptan, in rabbit.
AB  - MDL 74,721 (I), sumatriptan(II) and naratriptan(III) are new 5-HT1-like agonists
      that have potential as a novel treatment for migraine. Liquid chromatographic
      electrospray-mass spectrometric (LC-ESI-MS) assay have been developed to compare
      the pharmacokinetics of these three antimigraine compounds. The concentration of
      each parent drug was determined using a solid-phase extraction method and LC-ESI
      MS analysis demonstrating the high sensitivity and specificity of the methods
      down to subnanogram levels in rabbit plasma samples. Pharmacokinetic parameters
      evaluated after administration of single intravenous and oral doses were very
      similar and the ANOVA analysis did not show any statistically significant
      differences for t1/2, Cmax, V or AUC (normalised). The pharmacokinetic parameters
      showed short t1/2 (range 1.14-1.9 h) either after intravenous (i.v.) or oral
      (p.o.) administration and high total body clearance (CL) after the p.o. dose both
      probably due to extensive and rapid metabolism of the parent drugs as suggested
      by the low values for bioavailability (range 13.4-22.8%).

PMID- 9160270
TI  - An improved method for the simultaneous determination of losartan and its major
      metabolite, EXP3174, in human plasma and urine by high-performance liquid
      chromatography with fluorescence detection.

PMID- 9160272
TI  - Psychosomatic illnesses are not "all in the mind".

PMID- 9160271
TI  - Developing practical indexes of somatization for use in primary care.

PMID- 9160273
TI  - Depression, use of medical services and cost-offset effects.
AB  - This review considers evidence that depression is associated with increased use
      of general medical services and that more intensive treatment of depression might
      be expected to reduce medical expenditures. Cross-sectional studies strongly
      support an association between depression and medical utilization, but cannot
      establish a causal relationship. Available longitudinal studies lack the sample
      size and duration of follow-up necessary to examine how changes in depression
      influence utilization. Some quasi-experimental and experimental studies support a
      "cost-offset" effect due to mental health treatment, but no experimental data
      directly address the specific impact of depression treatment on medical
      utilization. The available data identify the potential for large cost savings
      through improved treatment of depression but do not clearly establish that such
      savings can be realized. Definitive proof of a cost-offset due to depression
      treatment will require a new generation of experimental studies adapted to assess
      economic outcomes.

PMID- 9160274
TI  - Why do adolescent girls watch their weight? An interview study examining
      sociocultural pressures to be thin.
AB  - Body concerns, dieting, and weight watching were examined in 30 year 10
      adolescent girls. Semistructured interviews consisting of open-ended and rated
      questions assessed descriptions of and reasons for weight loss attempts, with an
      emphasis on noting sociocultural influences. Audiotaped and transcribed
      interviews were assessed for themes, coded and rated. Findings suggested a strong
      role of sociocultural influences leading to both unhealthy and healthy body
      attitudes and eating behaviors. Media and fashion were reported to exert the
      strongest pressures to be thin for subjects. While a few subjects reported direct
      pressures to diet from friends and parents, indirect social influences were more
      common. These influences included social comparison, joint dieting and avoidance
      of social disapproval.

PMID- 9160275
TI  - Personality profile among symptomatic and recovered patients with neck sprain
      injury, measured by MCMI-I acutely and 6 months after car accidents.
AB  - The relationships between personality and psychiatric symptoms and long-lasting
      physical symptoms were assessed in 88 neck sprain patients injured in car
      accidents. The Millon Clinical Multiaxial Inventory (MCMI-I) was completed at
      time of occurrence (intake) and 6 months after the injury. The neck sprain
      patients were divided into three subgroups according to symptoms 6 months after
      the accident. In addition, the total neck sprain group was compared with three
      other subject groups. The results indicated that the three neck sprain subgroups
      did not differ on the MCMI-I neither at intake nor 6 months later. The total neck
      sprain patients group was significantly different from patients with major
      depression on all scales of the MCMI-I, but not significantly different compared
      to patients with localized musculoskeletal pain. Compared to a group of health
      personnel, there were only a few significant differences. The study does not
      support the view that premorbid personality traits can predict outcome for neck
      sprain patients.

PMID- 9160276
TI  - Physical fatigability and exercise capacity in chronic fatigue syndrome:
      association with disability, somatization and psychopathology.
AB  - Physical fatigability and avoidance of physically demanding tasks in chronic
      fatigue syndrome (CFS) were assessed by the achievement or nonachievement of 85%
      of age-predicted maximal heart rate (target heart rate, THR) during incremental
      exercise. The association with functional status impairment, somatization, and
      psychopathology was examined. A statistically significant association was
      demonstrated between this physical fatigability variable and impairment, and a
      trend was found for an association with somatization. No association was
      demonstrated with psychopathology. These results are in accordance with the
      cognitive-behavioral model of CFS, suggesting a major contribution of avoidance
      behavior to functional status impairment; however, neither anxiety nor depression
      seem to be involved in the avoidance behavior. Aerobic work capacity was compared
      between CFS and healthy controls achieving THR. Physical deconditioning with
      early involvement of anaerobic metabolism was demonstrated in this CFS subgroup.
      Half of the CFS patients who did not achieve THR did not reach the anaerobic
      threshold. This finding argues against an association in CFS between avoidance of
      physically demanding tasks and early anaerobic metabolism during effort.

PMID- 9160277
TI  - Greater emotional distress is associated with accelerated CD4+ cell decline in
      HIV infection.
AB  - An investigation was conducted to explore the relationship between emotional
      distress and HIV progression. One hundred twenty-five homosexual, HIV-positive
      males participated in a 12-month longitudinal investigation. Psychosocial data
      were collected at 6-month intervals and CD4+ data were collected from diagnosis
      to the end of the investigation. Principal component analyses were performed
      initially to identify factors of emotional distress and health status. In
      addition, CD4+ reliability assessments were performed to ensure the validity of
      the prognostic assessments made. As a result of these analyses, 47 individuals
      were eligible for the main analyses. The results from a stepwise regression
      revealed that disease progression was significantly predicted by CD4+ count at
      diagnosis (32% of variance) and emotional distress (17% of variance), but was
      unrelated to subjective perceptions of health. The data suggest that some of the
      variability in HIV progression can be attributed to emotional distress.

PMID- 9160278
TI  - Psychosocial factors related to emotional disturbances during pregnancy.
AB  - This study explored a multifactorial model for the understanding of the factors
      related to the intensity of prenatal emotional disturbances. Data were gathered
      from 213 pregnant women during the second trimester of pregnancy. Participants
      were assessed according to a number of psychosocial variables. Two types of
      prenatal emotional disturbances were examined: depressive symptoms and
      ambivalence and fears related to maternity. A path analysis indicated that four
      risk factor domains had a direct effect on depressive symptom level: locus of
      control; interpersonal relationships; stressors; and psychiatric history. Four
      risk factor domains also had a direct effect on the level of ambivalence and
      fears: sociodemographics; depressive symptom level; interpersonal relationships;
      and family history. Several factors showed an indirect effect on one or both of
      the disturbances. These results indicate that the study of factors related to
      prenatal emotional disturbances benefits from a multifactorial model assessing
      direct and indirect effects.

PMID- 9160279
TI  - Determination of future health status expectation in rheumatoid arthritis.
AB  - While examining the relationship between, neuroticism, somatic factors and future
      health status expectation in rheumatoid arthritis (RA) patients, the present
      study found a considerable level of pessimism in patients, which may be related
      to perceived limitation of the quality of life. However, psychosocial disposition
      (i.e., neuroticism) did not prove to be a crucial factor by which RA patients
      assessed their future health status expectation. These results may be important
      in future treatment procedures.

PMID- 9160280
TI  - Dextroamphetamine as a treatment for depression and low energy in AIDS patients:
      a pilot study.
AB  - This report documents findings from an open trial of dextroamphetamine in the
      treatment of depression and low energy in AIDS patients. Dextroamphetamine offers
      the potential for rapid onset of effect and activation properties, both of which
      are important to persons with late stage HIV illness. Primary inclusion criteria
      included having a DSM-III-R depressive disorder, debilitating low energy, CD4
      cell count below 200 cells/mm3, and no history of drug dependence. The trial
      consisted of open treatment in a 6-week protocol, with indefinite follow-up.
      Twenty-four men entered the study, 18 of 19 (95%) patients who completed at least
      6 weeks of treatment reported substantial improvement with regard to both mood
      and energy at a median dosage of 10 mg/day. These results suggest that
      dextroamphetamine is a potentially effective, fast acting antidepressant
      treatment for this population and call for a larger, controlled trial.

PMID- 9160281
TI  - Role of lipid-induced changes in plasma membrane in the biophysical shunt theory
      of psychopathology.
AB  - The existence of a lipid factor that either causes faulty lipid metabolism or
      directly contributes to the emergence of a biophysical shunt in neuronal membrane
      ionic flow propagation is proposed. The neuronal membrane contains a remarkable
      amount of phospholipids, glycolipids and cholesterol. It is assumed that, under
      certain unfavorable intrinsic states, the plasma membrane's lipid order and
      composition and, consequently, its cholesterol-to-phospholipid ratio, may change.
      This, in turn, may significantly modify membrane fluidity, altering the essential
      physical properties in the affected portions of the membrane and causing a
      disarray in the adjacent ion channels, leading to the establishment of a
      biophysical shunt in a loop-like operation, forming the basis for a variety of
      mental disorders. The present model offers a diet-induced lipid correction for
      the relief of psychopathological problems.

PMID- 9160282
TI  - Ascorbate availability and neurodegeneration in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis is a fatal neurodegenerative disease in which upper
      and lower motoneurons progressively deteriorate and die. Neuronal damage is most
      evident in the lower central nervous system, and death generally occurs following
      central respiratory failure. Proposed and demonstrated mechanisms for amyotrophic
      lateral sclerosis are diverse, and include altered superoxide dismutase and
      neurofilament proteins, autoimmune attack, and hyperglutamatergic activity.
      However, they do not account for the late onset of the disease, its earlier onset
      in males, and the differential vulnerability of neurons located in the brainstem
      and spinal cord. It is proposed here that, within the context of a specific
      defect such as altered superoxide dismutase, age-dependent decline in ascorbate
      availability triggers the disease. A role for ascorbate, which is found in
      millimolar levels in neurons, is suggested by a number of consistencies: 1)
      superoxide radicals being a common substrate for superoxide dismutase and
      ascorbate; 2) a close association between central nervous system ascorbate levels
      and injury tolerance; 3) a steady decline in ascorbate plasma levels and cellular
      availability with age; 4) plasma ascorbate levels being lower in males; 5) an
      association of ascorbate release with motor activity in central nervous system
      regions, in vivo; 6) the coupling of brain-cell ascorbate release with glutamate
      uptake; 7) possible roles for ascorbate modulation of N-methyl-D-aspartate
      receptor activity; 9) the ability of ascorbate to prevent peroxynitrite anion
      formation; and 10) evidence supporting the scorbutic guinea pig as a model for
      amyotrophic lateral sclerosis. Emphasis is placed on the probable competition
      between superoxide dismutase and ascorbate within the context of a primary defect
      of metal-binding or metal access in high-concentration proteins such as
      superoxide dismutase and human heavy neurofilaments. Finally, distinct features
      of alpha-motoneuronal physiology suggest that cell physiological characteristics
      such as high metabolic activity and extensive calcium dynamics may render neurons
      differentially vulnerable in amyotrophic lateral sclerosis.

PMID- 9160284
TI  - Urotherapy for patients with cancer.
AB  - Cancer cells release various antigens, some of which appear in the urine. Oral
      autourotherapy is suggested as a new treatment modality for cancer patients. It
      will provide the intestinal lymphatic system with the many tumor antigens against
      which antibodies may be produced. These antibodies may be pierced through the
      blood stream and attack the tumor and its cells.

PMID- 9160283
TI  - Up-regulation of IGF binding protein-1 as an anticarcinogenic strategy: relevance
      to caloric restriction, exercise, and insulin sensitivity.
AB  - The mitotic rate of stem cells is a major determinant of cancer risk. Insulin
      like growth factors (IGFs) are virtually obligate stimulants of cell turnover in
      nearly every tissue. IGF activity is subject to rapid modulation by hepatic
      release of IGF binding protein-1 (IGFBP-1), a factor whose synthesis is
      suppressed by insulin and increased by glucagon. Up-regulation of IGFBP-1
      production can be expected to decrease IGF activity and thereby diminish cancer
      risk. Measures that sensitize peripheral tissues to insulin, and thereby down
      regulate insulin secretion, can be expected to increase IGFBP-1 synthesis,
      provided that they do not unduly sensitize hepatocytes as well. Prolonged aerobic
      exercise and caloric restriction also increase IGFBP-1 production. Since IGF-1
      suppresses hepatic synthesis of sex hormone binding globulin (SHBG), down
      regulation of IGF activity will increase SHBG levels and thus diminish the
      availability of free sex hormones--an effect that should further decrease cancer
      risk in sex hormone-responsive tissues. These considerations rationalize many
      findings in animal and epidemiologic studies, and suggest that non-diabetic
      insulin resistance may be a significant cancer risk factor. Increased IGF
      activity associated with insulin resistance may also promote benign hyperplasias
      most notably atherosclerosis. Hyperinsulinemia stimulates intimal hyperplasia
      indirectly, via IGF.

PMID- 9160285
TI  - Sudden infant death syndrome and placental disorders: the thyroid-selenium link.
AB  - Placental insufficiency, inducing hypoxia-ischaemia, is considered a major cause
      of neuronal injury and impaired post natal development. Placental insufficiency
      alters the metabolism of arachidonic acid and its oxidation products. Premature
      labour and low-birth-weight infants are associated with reduced intrauterine
      blood-flow and infections of the reproductive tract. Thyroidal activity is
      depressed in undernutrition (placental insufficiency). Premature infants require
      extra vitamin C for normal tyrosine metabolism (tyrosine is the thyroxine
      precursor). Among the symptoms indicating infantile cretinism, which appear
      during 3-5 months of age are: delayed union of skull bones, torpid behaviour,
      slow feeding, cyanosis during feeding, excessive sleepiness, enlarged tongue,
      umbilical herniation, flabby musculature, short stature and delayed development.
      These symptoms have all been described in low-birth-weight infants and sudden
      infant death syndrome victims by various authors. Bacteria utilize selenium (at
      the expense of host tissue). Escherichia coli is among the bacteria invading the
      reproductive tract. E. coli produce thiouracil and are goitrogenic. Some strains
      of E. coli produce phospholipase A2 which releases arachidonic acid from
      phospholipids for prostaglandin synthesis. Phospholipase A2 is more active
      against peroxidized than non-peroxidized lipids. Bacterial competition for
      intrauterine selenium and goitrogenic bacterial infections of the reproductive
      tract during pregnancy, depress thyroid function in the fetus but not in the
      mother.

PMID- 9160286
TI  - Was the formation of 1,25-dihydroxyvitamin D3 initially a catabolic pathway?
AB  - Following solar ultraviolet radiation, epidermal 7-dehydrocholesterol is
      converted to previtamin D3, which then undergoes a thermal isomerization into
      vitamin D3. The metabolism of vitamin D3, which is usually considered as an
      inactive compound, gives rise to the active hormone 1,25-dihydroxyvitamin D3,
      following two hydroxylation steps occurring in liver and kidney. Here, we propose
      that this anabolic pathway can also be interpreted as a catabolic one leading to
      the degradation of the photoproducts of 7-dehydrocholesterol, for which a
      specific biological role in the skin is proposed.

PMID- 9160287
TI  - Homeostatic disturbances and human aggression.
AB  - A new model on the nature of human aggression is presented. It rests on the
      assumption that a pre-established organismic homeostatic modification, based on a
      decrease in neuronal membrane electric threshold, causes neural facilitation. In
      turn, this influences the cut-off phenomenon, in particular, neuronal network and
      therefore either inherited schemata representation, or acquired engram linkage
      programs run inadequately. These programs adjust the response to working loads of
      the eight normal serial stages in the body's operational regime activity. The
      effect of facilitation on these programs is: (1) loss of discrimination when
      approaching involuntary multi-stimuli; (2) the corruption of acquired engram
      linkage portions used in neural networks; (3) significant reduction of the
      voluntary degrees of freedom of response, thus narrowing the body's operational
      regime activity. This results in damage to certain cognitive links from some
      acquired engram linkages, enhancing impulse-like program mismatches and causing a
      unilateral 'fight' response of an aggressive nature.

PMID- 9160288
TI  - Sialorrhea in amyotrophic lateral sclerosis: a hypothesis of a new treatment-
      botulinum toxin A injections of the parotid glands.
AB  - The inhibitory action of botulinum toxin is not confined to the neuromuscular
      junction. The toxin has long been known to block all the autonomic cholinergic
      fibers, including the major secretomotor parasympathetic fibers to salivary
      glands. The parotids are the largest of the salivary glands and their selective
      chemodenervation with botulinum toxin A is likely to result in substantial
      reduction of saliva production. Injection of the parotid glands with botulinum
      toxin is proposed as an new treatment for sialorrhea in patients with amyotrophic
      lateral sclerosis and other neurological diseases.

PMID- 9160289
TI  - A liability theory of disease: the foundation of cell population pathology.
AB  - Within a homogeneous population of cells, the tendency of individual cells to
      become diseased is not 'homogeneous'. As a general concept of disease, the
      'liability theory' describes such a tendency (cell liability) as a quantitative
      characteristic following a continuous distribution. This suggests that there are
      always some cells that are more liable than the rest and that the liability
      values of cells or liability-associated cell characteristics can be assessed
      quantitatively. By defining the more or extremely liable cells through a critical
      value or 'threshold', the liability theory hypothesizes that these cells may play
      a significant role in determining or affecting the overall disease liability of a
      cell population; the more such cells are present, the more liable the cell
      population is, as a whole, to disease. Furthermore, it proposes that the origin
      and development of disease may be fundamentally relevant to this kind of
      intrapopulational variation in cell liability. The liability theory attempts to
      provide a theoretical framework for studying the 'cell population' mechanism of
      disease, or cell population pathology. Also, it may serve as a working model for
      analysis and assessment of cell population liabilities for various diseases.

PMID- 9160290
TI  - The placebo effect on mood and behavior: the role of the endogenous opioid
      system.
AB  - Evidence from clinical and experimental studies has shown that placebos influence
      mood and behavior, that endogenous opioids are involved in the placebo effect,
      and that the endogenous opioid system is related to psychological events. Recent
      studies have also demonstrated that the endogenous opioid system is closely
      connected with other neurotransmitter systems in the brain. The author suggests
      that the interaction between the endogenous opioid system and different
      neurotransmitter systems in the brain mediates the placebo effect on mood and
      behavior of both healthy and sick people.

PMID- 9160291
TI  - A role for photoproducts of vitamin D in the etiology of cutaneous melanoma?
AB  - Several clinical and epidemiological aspects of cutaneous melanoma seem anomalous
      because they contrast with other sunlight-associated skin cancers. For example,
      persons with the greatest risk of melanoma are not those with the greatest
      cumulative solar exposure, the anatomic areas that receive the most solar
      exposure are not preferentially affected, and the incidence of the disease is
      seasonal, with more cases reported in summer than winter. This article discusses
      the synthesis and biologic effects of vitamin D photoproducts and suggests that
      sun-related local skin effects, mediated by vitamin D photoproducts, on
      melanocytes previously damaged by excessive solar exposure may help explain the
      seemingly anomalous aspects of melanoma.

PMID- 9160292
TI  - Landscapes of longevity: the calcium-selenium-mercury connection in cancer and
      heart disease.
AB  - Cancer and heart disease display spatial patterns that suggest the possible
      involvement of calcium and selenium deficiencies and mercury excess in their
      aetiologies. As a consequence, longevity tends to be most common in regions where
      the environment is calcium- and selenium-enriched but contains only low levels of
      mercury. Examples are cited from West Africa, China, England and the USA.

PMID- 9160293
TI  - Midline teratomas, mullerianosis, the multifariousness of gynaecological
      neoplasias, and the scrotum. Are they manifestations of a germ-soma barrier?
AB  - Empirical evidence and theoretical considerations suggest that there are
      mechanisms protecting the germ line from untoward somatic influences. In the
      intraorganismal competition between cell lineages, evolution will give priority
      for protection to the germ line, which carriers the heritable genes. In
      embryogenesis, germ cells migrate along the midline as this is an area where
      developmental influences are lower; exposure to somatic factors may cause
      inception of teratomas. In order not to hinder the germ line, the female genital
      tract has a reduced level of cell determination, which results in the
      multifariousness of gynaecological proliferations, including mullerianosis. The
      external location of testes reduces somatic constraints on spermatogenesis.

PMID- 9160294
TI  - Left-right asymmetry and mirrors.

PMID- 9160295
TI  - Temperature dependent expression of an acid phosphatase by Bordetella
      bronchiseptica: role in intracellular survival.
AB  - Bordetella bronchiseptica has the ability to invade and survive intracellularly.
      This potential to survive for extended periods within eukaryotic cells might play
      an important role in the pathogenesis of the infections caused by this
      microorganism. The bacterial factors involved in this process, however, have not
      yet been determined. In this study we have identified an acid phosphatase
      produced by B. bronchiseptica, but not by other Bordetella spp. The expression of
      this enzyme was demonstrated to be strictly regulated by temperature (optimal
      expression at 30 degrees C) and seems to be partially repressed by the product of
      the bvg locus. The enzyme was localized in the cytoplasmic fraction, the optimal
      activity was observed at pH 5.5, and the apparent molecular mass obtained by
      zymogram was 40 kDa. To further investigate the pathogenic role of this enzyme,
      mutants lacking acid phosphatase activity were obtained from both bvg-positive
      and bvg-negative parental strains using minitransposons. The growth pattern of
      these recombinant clones in vitro was similar to the parent strains, however, the
      tested clones exhibited a significant reduction (P < or = 0.05) in their
      intracellular survival ability. This newly described acid phosphatase from B.
      bronchiseptica seems to play a role in intracellular survival, and therefore
      represents a novel pathogenicity factor.

PMID- 9160296
TI  - Induction of human endothelial tissue factor expression by Neisseria
      meningitidis: the influence of bacterial killing and adherence to the
      endothelium.
AB  - Tissue factor (TF), a small membrane bound high affinity receptor for factor VII,
      has an important procoagulant role in the haemostatic dysfunction associated with
      severe sepsis. Using an in vitro model of human endothelial TF expression,
      defined strains of Neisseria meningitidis were found to upregulate endothelial
      cell procoagulant activity (PCA) in a dose dependent manner. This TF response was
      detected with as little as 10(4) cfu/ml and reached similar levels to those seen
      with high concentrations of purified endotoxin (> 1 ng/ml). Treatment of N.
      meningitidis with either adult donor immune serum, penicillin or gentamicin
      failed to enhance this PCA. Limulus amoebocyte lysate assay of lipopolysaccharide
      in bacterial culture filtrates together with polymyxin B inhibition experiments
      suggest that endotoxin is largely responsible for endothelial TF induction by N.
      meningitidis. Incubation of endothelial cells with N. meningitidis B1940 and
      B1940 siaD- (an eight-fold more adherent unencapsulated isogenic strain),
      revealed a significantly greater TF response to B1940 siaD- (P < 0.01). In
      conclusion, bacterial adhesion to the vessel wall and therefore local levels of
      endotoxin may be important determinants of the endothelial procoagulant response
      to N. meningitidis and the consequent coagulopathy commonly associated with the
      disease.

PMID- 9160297
TI  - Isolation of alpha-toxin, theta-toxin and kappa-toxin mutants of Clostridium
      perfringens by Tn916 mutagenesis.
AB  - Clostridium perfringens is the causative agent of clostridial myonecrosis or gas
      gangrene and mediates infection and disease by producing numerous extracellular
      toxins, including alpha-toxin, theta-toxin and kappa-toxin. Tn916-mutagenesis was
      used to isolate mutants defective in their ability to produce either alpha-toxin
      or theta-toxin. Nine independently derived mutants were isolated. In four of
      these mutants Tn916 had inserted at sites located 193 bp or 198 bp upstream of
      the theta-toxin structural gene, pfoA. Four mutants contained large deletions,
      three in regions which encompassed the theta-toxin structural and regulatory
      genes pfoA and pfoR, respectively, and the kappa-toxin structural gene, colA, and
      one in a region encompassing the alpha-toxin structural gene, plc. These mutants
      should prove to be invaluable for further genetic studies aimed at determining
      the role of these toxins in virulence.

PMID- 9160298
TI  - Role of bacteria in the pathogenesis of short bowel syndrome-associated D-lactic
      acidemia.
AB  - Previously, we have demonstrated that short bowel syndrome (SBS) patients suffer
      daily from D-lactic acidemia; in these patients rather high amounts of
      (bacterial) D-lactate emerge in blood and urine with a circadian rhythm. The aim
      of this study was to establish the microbial basis of D-lactic acidemia in SBS.
      Therefore, faecal flora of (young and adult) SBS-patients was analysed
      qualitatively and quantitatively, and compared to that of controls. The isolated
      bacterial species were screened for massive D- and/or L-lactate production after
      in vitro growth. After introduction of oral feeding in SBS-infants shortly after
      the resection, lactobacilli increased from < or = 1% up to 60 +/- 5% of the
      faecal flora within 2-3 weeks. In the faeces of patients with oral feeding the
      lactate producers Lactobacillus acidophilus and Lactobacillus fermentum were the
      major resident bacteria (each with 10(10)-10(12) cfu/g faeces). During active
      growth in vitro these lactobacilli produced massive amounts of D- and L-lactic
      acid from glucose. Use of oral antibiotics in two SBS-children did not reduce the
      total numbers of lactobacilli, but caused shifts within the intestinal
      populations of at least lactobacilli. It is concluded that the strongly reduced
      intestinal capacity for carbohydrate absorption and the oral consumption of
      easily fermentable carbohydrates form the physiological basis for D-lactic
      acidemia in SBS, and that the fermentative D-lactate production by intestinal
      bacteria, especially the abundant, resident lactobacilli, forms its microbial
      basis. In these patients the antimicrobial and therapeutic effects of antibiotics
      are unpredictable.

PMID- 9160299
TI  - Phenotypic variants of meningococci and their potential in phagocytic
      interactions: the influence of opacity proteins, pili, PilC and surface sialic
      acids.
AB  - In previous studies we have examined the roles of meningococcal surface
      structures (capsule, lipopolysaccharides, pili and opacity proteins: Opa and Opc)
      in bacterial interactions with human epithelial, endothelial and mononuclear
      phagocytic cells. In the current investigations, using defined derivatives of a
      serogroup A strain C751 and a serogroup B strain MC58, we studied the roles of
      these structures with human polymorphonuclear phagocytes (PMN). In addition, we
      examined the potential influence of the pilus-associated protein, PilC,
      previously known to affect epithelial cell interactions. The data show, that, as
      with monocytes, opacity proteins affect bacterial interactions with PMN and
      require surface sialic acids (on capsule and LPS) to be down-modulated in order
      to function. Also, in contrast to their role in human epithelial and endothelial
      adherence, neither pili nor PilC expression had any effect on phagocytic cell
      interactions with respect to induction of chemiluminescence as well as phagocytic
      killing. Examination of the relative influence of Opa and Opc indicated that Opa
      proteins are more effective than Opc in PMN interactions whereas the reverse was
      the case with monocytes. These results suggest that Opa and Opc mediate
      interactions with phagocytic cells via distinct mechanisms. Observations
      presented here and reported previously collectively show that the structural
      requirements of meningococci for interacting with phagocytes, in the absence of
      opsonins, are present in the phenotype which is often isolated from the
      nasopharynx (asialylated, piliated, Opa/Opc+) whereas the phenotype prevalent in
      the blood (sialyted, piliated, Opa/Opc+) retains the ability to adhere to
      endothelial cells (via pili) but appears to be refractory to interactions with
      phagocytic cells.

PMID- 9160300
TI  - Local transient induction of inflammatory cytokines after intranasal
      administration of recombinant Bordetella pertussis.
AB  - Inflammatory cytokines have been described to play a critical role in the
      orientation and amplification of the IgA immune response. In this study, we show
      that the intranasal administration of a Bordetella pertussis strain expressing
      the protective antigen glutathione-S-transferase of Schistosoma mansoni (Sm28GST)
      induced an inflammatory response in the lungs of mice, characterized by the
      production of inflammatory cytokines, such as Tumor Necrosis Factor alpha,
      Interleukin-6 and Transforming-Growth Factor beta. The production and the
      secretion of these cytokines in lung tissues were early and transient. Their
      presence was observed only during the first week after administration despite the
      persistence of the bacteria for 1 month. Two weeks after inoculation, Interleukin
      10 secretion was detected in the lungs, which could explain the decrease in the
      production of inflammatory cytokines. These inflammation-regulating cytokines,
      induced in the lungs by the presence of the bacterial vector, could be part of
      the process generating the local immune response, in particular the anti-Sm28GST
      IgA response.

PMID- 9160301
TI  - Complement resistance of capsulated strains of Aeromonas salmonicida.
AB  - The complement resistance of Aeromonas salmonicida strains grown under conditions
      promoting capsule formation was investigated using well characterized strains and
      their isogenic mutants. Complement resistance was previously studied using the
      same strains growing under non-capsulating conditions. The serum resistant
      strains were found to activate complement, but rapidly degrade C3b preventing
      productive formation of the lytic complex C5b-9. Isogenic lipopolysaccharide
      rough mutants grown under non-capsulating conditions were serum sensitive,
      binding a large amount of C3b and leading to productive formation of C5b-9. When
      grown under conditions promoting capsule formation, these mutants were partially
      resistant to complement because less C3b is bound to them and also partially
      degraded, with a concomitant reduction in lytic C5b-9.

PMID- 9160302
TI  - Non-neoplastic epithelial alterations of the vulva: recognition assessment and
      comparisons of terminologies used among the various specialties.
AB  - To assess the recognition of non-neoplastic epithelial alterations of the vulva
      and to compare terminologies used for these lesions by various specialties, we
      performed a clinical and dermatopathologic review of all of the cases diagnosed
      as non-neoplastic epithelial alterations of the vulva that were followed by one
      gynecologist. Forty-five initial clinical and pathologic diagnoses made by a
      group of 14 general surgical pathologists during a 15-year period were compared
      to the diagnoses made by two dermatopathologists at the time of review.
      Comparison of diagnoses between the three specialties revealed two types of
      disparities. The first represented differences in nomenclature. Although all
      parties frequently agreed on a diagnosis of lichen sclerosus, which represented
      the most frequent histologic diagnosis, the dermatopathologists did not use the
      term squamous hyperplasia for any case. Of greater significance was the second
      type of disparity identified, i.e., failure of the gynecologist and general
      surgical pathologist to identify uncommon dermatoses in eight cases. Concordance
      in diagnosis among the dermatopathologists was found in 43 of the 45 cases. These
      findings are consistent with the view that non-neoplastic epithelial alterations
      of the vulva are the same as elsewhere in the skin and that terms such as vulvar
      dystrophy or squamous hyperplasia are not meaningful or helpful in identifying or
      treating vulvar dermatoses. Unfamiliarity with specific dermatoses and the
      modified appearance of a dermatosis when occurring on the vulva might cause
      recognition failure by the gynecologist and general surgical pathologist. Entity
      recognition might be greatly improved if non-neoplastic vulvar lesions are
      approached as specific dermatoses rather than being labeled as squamous
      hyperplasias or vulvar dystrophies. Careful histories and physical examinations
      aid in identifying less common vulvar dermatoses. Referral to a
      dermatologist/dermatopathologist is indicated when the diagnosis is in doubt or
      if the response to treatment is poor.

PMID- 9160303
TI  - Comparison of topoisomerase II alpha and MIB-1 expression in uterine cervical
      squamous lesions.
AB  - The aim of this study was to assess the role of MIB-1 in the classification of
      cervical squamous lesions and to compare it with a novel proliferation marker,
      topoisomerase II alpha (TP II alpha). We classified 46 archival uterine cervical
      cases into 6 groups: normal (n = 3); human papillomavirus (n = 15); mild (n =
      10), moderate (n = 7), and severe (n = 6) cervical intra-epithelial neoplasia;
      and invasive carcinoma (n = 5). The formalin-fixed, paraffin-embedded tissue
      sections were stained with monoclonal antibodies to Ki-67 (MIB-1) and TP II alpha
      with a standard streptavidin immunohistochemical technique, with antigen
      retrieval to assess enzyme presence. The results were based on nuclear staining
      and percentage of positivity. We found that the mean percentage of positive
      nuclei increased from normal through increasing grades of dysplasia to its
      maximal level in invasive carcinoma. The level of positive nuclei in the
      epithelium also generally increased from basal to full thickness with progression
      of the lesions. The correlation between the percentage of nuclei positive for
      both antibodies with the use of linear regression was close, with an r value of
      0.85. Our conclusions were that MIB-1 is an adjunct in the classification of
      squamous lesions of the uterine cervix and that TP II alpha is a useful
      proliferation marker in this setting.

PMID- 9160304
TI  - Immunophenotypic analysis of ovarian and testicular Mullerian papillary serous
      tumors.
AB  - Intratesticular Mullerian papillary serous tumors lacking stromal invasion are
      uncommon neoplasms whose immunophenotypic properties have not been studied
      extensively. We present such information here and compare it with information
      from a group of ovarian papillary serous tumors of low malignant potential
      ("borderline serous tumors") that are morphologically identical. We compared the
      histologic features of our index case of intratesticular Mullerian papillary
      serous tumor with those of nine ovarian papillary serous tumors. We then
      evaluated both the index case and the ovarian tumors with antibodies against
      carcinoembryonic antigen, LeuM1, CA125, estrogen receptors, progesterone
      receptors, cytokeratin 7, and cytokeratin 20, by use of established
      immunohistochemical techniques. The testicular and ovarian tumors were
      morphologically indistinguishable. The intratesticular Mullerian papillary serous
      tumor expressed LeuM1, CA125, estrogen receptors, progesterone receptors,
      cytokeratin 7, and weak cytokeratin 20; carcinoembryonic antigen was not
      expressed. All of the ovarian papillary serous tumors expressed CA125, estrogen
      receptors, and cytokeratin 7. Eight of nine expressed progesterone receptors.
      Five of nine stained with LeuM1. Two of nine were focally weakly positive with
      cytokeratin 20. LeuM1 expression helps distinguish testicular papillary serous
      tumors from mesothelial proliferations, which might seem morphologically similar.
      The immunophenotype of intratesticular and female genital papillary serous tumors
      is similar; this similarity extends to expression of estrogen and progesterone
      receptors, which is rare in neoplasms in men, especially among testicular
      neoplasms.

PMID- 9160305
TI  - The role of follicular and interdigitating dendritic cells in HIV-related
      lymphoid hyperplasia: localization of fascin.
AB  - Fascin is a 55-kDa, actin-bundling protein expressed in follicular and
      interdigitating dendritic cells (DCs). Because these cells play a pivotal role in
      the pathogenesis of human immunodeficiency virus-related lymphoid hyperplasias
      (HLP), we evaluated them in 49 cases by immunohistochemical localization of
      fascin, and we related the findings to the histologic stage of disease. Fifteen
      cases of early HLP revealed strong localization of fascin within DCs of
      hyperplastic follicles and intense staining in interdigitating DCs and their
      processes in the interfollicular zones. Some follicles revealed focal disruption
      of the fascin-positive dendritic framework. DCs were also aligned beneath the
      peripheral sinuses of the node. In 15 cases of progressive HLP with partial
      follicular involution, 3 cases revealed findings similar to those described
      above. Twelve cases revealed loss of follicular dendritic staining, which was
      moderate in five cases and marked in seven. Residual clusters of DCs remained
      after partial dissolution. Interfollicular dendritic staining was reduced in 13
      cases, and perisinusoidal staining was reduced in 7. In late-stage HLP, staining
      of both follicular and interdigitating DCs was reduced or absent. Nine cases of
      diffuse immunoblastic or angioimmunoblastic lymphadenopathy-like proliferation
      had markedly reduced or absent follicular DCs, but prominent staining was present
      in interfollicular DCs, which formed a meshwork throughout the node in eight
      cases. Two cases of hyaline-vascular lymphoid hyperplasia had increased
      follicular DCs forming a tight syncytial network. In most cases, there was
      reduction of dendritic fascin-expressing cells with advanced disease and
      destruction of the dendritic framework of the node. Diffuse hyperplasia of fascin
      positive interdigitating cells occurred in cases with angioimmunoblastic
      morphologic features, and cases of hyaline-vascular lymphoid hyperplasia had
      increased follicular dendritic histiocytes forming a tight syncytial network.
      Destruction of DCs and, in some cases, interdigitating cell hyperplasia might be
      associated with the variable clinical course of HLP.

PMID- 9160306
TI  - p53 mutations in multiple urothelial carcinomas: a molecular analysis of the
      development of multiple carcinomas.
AB  - The purpose of this study is to assess whether the development of synchronous
      and/or metachronous multifocal urothelial cancers is due to field defect,
      intraluminal seeding and implantation, or both. We used a series of 42 cases of
      multiple urothelial cancers. We performed polymerase chain reaction single-strand
      conformation polymorphism, DNA sequencing, and immunohistochemical studies on p53
      gene mutations in 84 multiple urothelial carcinomas (78 urinary bladder
      carcinomas and 6 ureteric or renal pelvic carcinomas) from 42 patients. p53
      Mutations were detected in 42 (50%) of 84 cancerous tumors from 22 (52%) of the
      42 patients and were strongly related to the tumor grade but not to the tumor
      stage. Nine patients had identical mutations with or without additional mutations
      in the multiple carcinomas, which suggests that the carcinomas had a common
      origin. Eleven patients, however, had discordant mutations, and two patients had
      a mutation in one tumor but not in another, a fact that strongly suggests
      independent origin. Double mutations were observed in 9 (21%) of 42 patients; in
      these types of mutation, transitions were clearly more frequent than
      transversions, a difference from previously reported spectra of urothelial
      carcinomas. The data indicate that multiple urothelial carcinomas seem to be
      either common or of independent origin. In addition, the different p53 mutational
      spectra in this series might reflect the presence of other possible mutagens in
      carcinogenesis of multiple urothelial carcinomas.

PMID- 9160307
TI  - Inflammatory malignant fibrous histiocytoma: distinction from Hodgkin's disease
      and non-Hodgkin's lymphoma by a panel of leukocyte markers.
AB  - Inflammatory malignant fibrous histiocytoma (IMFH), consisting of large, atypical
      histiocyte-like cells set amidst an inflammatory backdrop of eosinophils,
      neutrophils, lymphocytes, and xanthoma cells, can be difficult to distinguish
      from Hodgkin's disease and non-Hodgkin's lymphoma, particularly of the Ki-1
      anaplastic large-cell type in small biopsy specimens. This problem is becoming
      more prevalent with the use of needle biopsies guided by computed tomography for
      definitive diagnosis. For this reason, we studied the expression of a battery of
      leukocyte markers in IMFH to evaluate whether they could serve as an
      independently reliable means of distinguishing amongst the three neoplasms. Eight
      examples of histologically typical IMFH were stained with a number of leukocyte
      markers that included CD30 (BerH2), CD15 (leuM1), CD45/ CD45RB (2B11,PD7/26/16),
      CD43 (leu 22), CD45RO (A6), CD20 (L26), and CD68 (KPI). The large anaplastic
      tumor cells within IMFH consistently lacked CD30, CD15, CD45/CD45RB, CD43,
      CD45RO, and CD20. In one case, the anaplastic cells expressed CD68. Benign
      histiocytes within IMFH expressed CD68 and displayed variable expression of CD15,
      CD45/CD45RB, and CD43. The reactive lymphocytes consisted mostly of scattered
      small T cells with a few B cells, mainly within lymphoid aggregates. We conclude
      that the immunophenotypic profile of the anaplastic cells in IMFH (lack of CD15,
      CD30, CD43, CD45/CD45RB, CD45RO, CD20) differs from most cases of Hodgkin's
      disease (ICD30+, CD15+/-) and from Ki-1 anaplastic large cell lymphoma (CD30+,
      CD45/CD45RB+/-, CD43+/-, CD45RO+/-, CD20-/+). Immunohistochemistry is an
      important diagnostic adjunct, provided care is taken to exclude benign
      histiocytes and inflammatory cells from consideration.

PMID- 9160308
TI  - Extrapleural solitary fibrous tumor: a report of seven cases.
AB  - Solitary fibrous tumors (SFTs) are rare, spindle-cell neoplasms generally
      associated with the serosal surface, especially the pleura. Histopathologic,
      immunohistochemical, ultrastructural, and flow cytometric analyses were performed
      on seven SFTs of extrapleural sites (two retroperitoneal, two soft tissue, one
      each peritoneal, nasal cavity, and orbit). Five patients were women, and two were
      men, aged from 21 to 68 years (average, 39 yr). All of the lesions presented as
      well-circumscribed masses. The lesions ranged in size from 2 to 20 cm in greatest
      diameter. Histologically, these lesions were entirely comparable to the pleural
      SFTs and lacked the characteristic features of other recognized neoplasms that
      occur in these regions. One tumor contained pleomorphic and round-cell
      sarcomatous foci. Immunohistochemically, all of the tumors were strongly positive
      for vimentin and CD34. Six of the seven tumors showed varying numbers of spindle
      cells positive for alpha smooth muscle actin, HHF35, neuron-specific enolase, Leu
      7, or glial fibrillary acidic protein. Ultrastructural examinations of three
      tumors showed that they were composed of primitive mesenchymal or fibroblast-like
      cells. Six tumors examined were diploid by flow cytometric examination. Clinical
      follow-up in six patients ranged from 1 to 7.5 years (average, 2.6 yr) and showed
      that five patients remained well with no evidence of disease after excision and
      that the patient with the sarcomatous elements died of recurrence 2.5 years after
      surgical treatment. These findings suggest that SFTs represent ubiquitous
      neoplasms of fibroblasts or primitive mesenchymal cells with aggressive
      potential.

PMID- 9160309
TI  - CD34 expression by inflammatory fibroid polyps of the stomach.
AB  - The phenotype of the proliferated spindled cells and the histogenesis of
      inflammatory fibroid polyp (IFP) have been a matter of debate. To clarify the
      immunohistochemical profile of the main cellular component, we reviewed
      histologically and studied immunohistochemically 11 cases (12 lesions) of IFP of
      the stomach. The lesions ranged in size from 0.4 to 3.0 cm (mean, 1.0 cm). All of
      the IFPs occurred in the antrum. Seven cases (63.6%) were accompanied by
      carcinoma or adenoma, which in two cases was present in covering epithelium.
      Grossly, eight IFPs were sessile, and four were polypoid. Microscopically, seven
      (58.3%) occupied both the mucosa and submucosa. Four (33.3%) were confined to the
      mucosa, and one was localized only in the submucosa. They were characterized by
      proliferation of relatively uniform spindled cells, often in a whorl-like
      arrangement around the blood vessels and glands. Eosinophilic and lymphocytic
      infiltration of varying degree was always present. The spindled cells in all of
      the IFPs were diffusely immunoreactive for vimentin and CD34. Seven (58.3%) were
      focally positive for histiocytic markers, such as KP1 and HAM56. Three (25%)
      showed focal immunoreactivity for alpha smooth muscle actin. Cytokeratin, desmin,
      S100 protein, Factor VIII RAG, and Ki-67 were negative in these spindled cells.
      The principle proliferating cells in IFPs in this study showed variable degrees
      of histiocytic and myofibroblastic lines of differentiation. Under the influence
      of some etiologic factors, the primitive, uncommitted spindled mesenchymal cells
      exhibiting CD34 immunoreactivity around the blood vessels and glands in the lower
      portion of mucosa and submucosa might play a role in development of IFP.

PMID- 9160310
TI  - Laser scanning cytometric analysis of cyclin B1 in primary human malignancies.
AB  - Cyclins are key components of the cell cycle progression machinery. They activate
      their partner-dependent kinases (CDKs) and target them to respective substrate
      proteins within the cell. CDK-mediated phosphorylation of specific sets of
      proteins drives the cell through particular phases or checkpoints of the cell
      cycle. During unperturbed growth of normal cells, the timing of expression of
      several cyclins is discontinuous, occurring at discrete and well-defined periods
      of the cell cycle. Immunocytochemical detection of cyclins in relation to cell
      cycle position (DNA content) by multiparameter flow cytometric techniques has
      provided a new approach to cell cycle studies. This approach, like no other
      method, can be used to detect the "unscheduled" expression of cyclins, namely,
      the presentation of G1 cyclins by cells in G2/M and of G2/M cyclins by G1 cells,
      without the need for cell synchronization. By use of multiparameter flow
      cytometric and laser scanning cytometric analysis, we correlated the expression
      of cyclin B1 with cell cycle position in normal lymphocytes stimulated to
      proliferate by the mitogen phytohemagglutinin and in 28 primary human tumors of
      different organ and type. Eighteen of the 28 tumors expressed the cyclin B1 in
      more than 5% of cells (B1 positive), and the rest showed cyclin expression from
      2.1 to 5% (B1 negative). In normal lymphocytes, the expression of cyclin B1 was
      restricted to very late S and G2 + M phases of the cell cycle. In 15 of 18
      primary tumors studied, the expression of cyclin B1 was "unscheduled"
      (unrestricted to particular phases of the cycle). The data suggest that the
      "unscheduled" expression of cyclin B1 might be a common defect in neoplasia.

PMID- 9160311
TI  - Pulmonary pathology of patients treated with partial liquid ventilation.
AB  - Initial trials of partial liquid ventilation (PLV), which is gas ventilation of
      perfluorocarbon-filled lungs, are underway in patients with severe respiratory
      failure. We report the first study of the effects of the perfluorocarbon,
      perflubron, on the lung. Necropsies were conducted in nine patients (seven adults
      and two neonates; mean adult age, 31 +/- 5 yr) managed with PLV (average number
      of doses, 4 +/- 1). All of the patients required extracorporeal life support. The
      patients had pneumonia with the acute respiratory distress syndrome (six
      patients), trauma/capillary leak syndrome (one patient), congenital diaphragmatic
      hernia (one patient), and primary pulmonary hypertension (one patient). Nine
      adult patients (mean age, 37 +/- 5 yr) with acute respiratory distress syndrome
      requiring extracorporeal life support served as a control. Pathologic findings
      were evaluated in both groups. Lung weights in the adult patients of both groups
      were elevated (mean weight of PLV-treated right lung, 1401 +/- 186 g; mean weight
      of PLV-treated left lung, 1131 +/- 177 g; mean weight of control right lung, 1018
      +/- 91 g; mean weight of control left lung, 988 +/- 80 g). There was no
      significant difference between the two groups (right lung, P = .066; left lung, P
      = .436). Frequent gross findings included focal consolidation, patchy hemorrhage,
      and glassy cut surfaces. The histologic findings were similar in both groups.
      Diffuse alveolar damage (either proliferative phase or mixed proliferative and
      exudative phases) was seen in all nine of the study patients. Eight of the nine
      control patients had diffuse alveolar damage (five had proliferative phase only,
      one had mixed proliferative and exudative phases, and two had exudative phase
      only). One other patient had extensive parenchymal necrosis. Other frequent
      findings were intra-alveolar hemorrhage, numerous intra-alveolar macrophages, and
      organization of exudate. PLV with perflubron in patients with adult and neonatal
      respiratory distress syndromes is not associated with unique pathologic findings
      in the human lung.

PMID- 9160312
TI  - Prevalence of pulmonary atypical alveolar cell hyperplasia in an autopsy
      population: a study of 100 cases.
AB  - A precursor lesion of pulmonary adenocarcinoma has not been clearly defined.
      Previous studies suggested that atypical alveolar cell hyperplasia (AACH) might
      represent such a precursor lesion. Most previous studies showed an association
      between AACH and adenocarcinoma in surgical resection specimens. In this study,
      we searched for the prevalence of AACH and nonatypical alveolar cell hyperplasia
      (ACH) in a general autopsy population. Cases in which there was clinical or
      anatomic evidence of pulmonary neoplasia were excluded from the study. In the 100
      consecutive autopsies examined, we found four cases of ACH and two cases of AACH.
      The two AACH lesions showed cytologic atypia and stained positively for p53 and c
      erb-2. These findings suggest a possible role for AACH as a precursor lesion of
      adenocarcinoma of the lung.

PMID- 9160313
TI  - Increased hepatic iron in the acquired immunodeficiency syndrome: an autopsy
      study.
AB  - Abnormalities in iron metabolism have been reported in patients with acquired
      immunodeficiency syndrome (AIDS). To assess the frequency of abnormal hepatic
      iron deposition in these patients and to examine potential causes of iron
      overload, we analyzed the amount of iron at different cellular sites in liver
      sections obtained at autopsy of 78 patients with AIDS. Quantitation of serum iron
      and transferrin levels and estimation of total iron binding capacity was obtained
      using serum from 63 patients. The number of whole blood/packed red blood cell
      transfusions and opportunistic infections was recorded. Of the 78 patients, 25
      (32%) showed a Grade 3 or 4 (0-4 scale) iron level, distributed in three
      patterns, i.e., in hepatocytes only, in hepatocytes and Kupffer cells, and in
      Kupffer cells only. In these 25 livers, 4 had cirrhosis, with no documented
      cause; the mean number of transfusions was 12.5; and 16 (64%) had Mycobacterium
      avium-Mycobacterium intracellulare infection. In the 53 livers with little or no
      iron, 5 had cirrhosis, with 3 of those 5 listing alcoholic liver disease or
      hepatitis as the cause; the mean number of transfusions was 1.4; and 18 (34%) had
      Mycobacterium avium-Mycobacterium intracellulare infection. Transferrin
      saturation was more than 50% in 6 (29%) of 21 cases with increased hepatic iron
      levels and in 6 (14%) of 42 cases with little or no hepatic iron. These results
      indicate that hepatic iron overload in patients with AIDS is associated with
      blood transfusions, an elevated transferrin saturation, and Mycobacterium avium
      Mycobacterium intracellulare infection. Significant hepatic iron deposition in
      patients with AIDS with no other apparent cause of cirrhosis suggests an
      etiologic role for iron in hepatic injury. The increase in hepatic iron levels in
      these patients has potentially adverse clinical effects related to the use of
      transfusions, iron supplements, and iron-containing drugs.

PMID- 9160314
TI  - Trisomy 3 in renal cell carcinoma.
AB  - Particular chromosomal aberrations have been associated with specific histologic
      types of renal cell carcinoma (RCC). To date, trisomy 3 has rarely been
      described, and this aberration has not been associated with any specific
      pathologic features. Herein, we report the cytogenetic analysis of 16 primary
      RCCs, including 8 papillary and 8 clear-cell primary tumors and 1 recurrent
      papillary tumor. Trisomies of chromosome 7 (7 of 8 tumors), 17 (7 of 8), 16 (7 of
      8), and 20 (4 of 8) were frequent in primary papillary RCC, and deletions of
      chromosome 3p were detected in 7 of 8 clear-cell RCCs. Trisomy 3 was detected in
      five of eight papillary RCCs and was commonly associated with other trisomies.
      Trisomy 3 was an isolated finding in one of eight clear-cell RCCs. Four of five
      papillary RCCs with trisomy 3 had abundant intracytoplasmic hemosiderin, four of
      five were low grade, and all 5 were organ confined. The single clear-cell tumor
      with trisomy 3 had no other cytogenetic aberrations, also had abundant
      intracytoplasmic hemosiderin, and was also low grade and low stage. The recurrent
      papillary RCC did not have trisomy 3. We conclude that trisomy 3 is present in
      some RCCs and might be associated with low-grade, low-stage, papillary tumors
      with intracytoplasmic hemosiderin.

PMID- 9160316
TI  - Malignant melanoma of the soft parts (clear-cell sarcoma): confirmation of EWS
      and ATF-1 gene fusion caused by a t(12;22) translocation.
AB  - We report on the cytogenetic and molecular analysis of a malignant melanoma of
      the soft parts (MMSP). A t(12;22)(q13;q12) was found as the only structural
      chromosomal change, and this provides additional support for the important role
      of this translocation in MMSP development. Molecular analysis revealed in frame
      fusion between exon 10 of the Ewing's sarcoma oncogene (EWS) and codon 110 of ATF
      1. In previously analyzed MMSPs, junctions were observed between EWS exon 8 and
      ATF-1 codon 65. The present data thus indicate that, as in Ewing's sarcoma,
      different fusion proteins can occur in MMSP. The presence of the EWS/ATF-1 fusion
      gene in the tumor cells was demonstrated by dual color fluorescence in situ
      hybridization on interphase nuclei. Our data provide additional support for the
      specific association of the t(12;22) and the resulting EWS/ATF-1 gene fusion in
      MMSP. This particular genetic aberration, therefore, serves as a strong
      diagnostic marker for MMSP. We conclude that detection of the t(12;22) by
      cytogenetic or molecular analysis is useful in establishing or confirming the
      diagnosis of MMSP.

PMID- 9160315
TI  - Integrated expression of glomerular extracellular matrix proteins and beta 1
      integrins in monoclonal light chain-related renal diseases.
AB  - Light-chain deposition disease (LCDD) and amyloid light-chain amyloidosis (AL-Am)
      represent the two classical diseases associated with glomerular alterations in
      monoclonal light chain-related renal diseases. LCDD is characterized by
      deposition of extracellular matrix proteins in the mesangium, thus creating the
      morphologic appearance recognized as nodular glomerulosclerosis. In AL-Am, the
      mesangial matrix is replaced by polymerized light chains in the form of amyloid
      fibrils. Integrins are responsible for cell-to-cell and cell-to-matrix
      communication and, therefore, are expected to play a key role in the alterations
      encountered in these two diseases. The present article addresses the expression
      of selected extracellular matrix proteins (collagen IV, laminin, fibronectin, and
      tenascin) and their respective receptor beta 1 integrins (alpha 2, alpha 3, alpha
      5, and alpha 9) in glomeruli with LCDD and AL-Am by immunohistochemical methods.
      The corresponding integrin (alpha 9 beta 1) co-localized with tenascin in the
      center of the mesangial nodules in LCDD. In AL-Am, tenascin is found primarily at
      the periphery of replaced mesangial areas and in the remaining mesangium not
      replaced by the amyloid. Tenascin co-localized with alpha 9 beta 1 integrin in
      mesangial areas in the earlier phases of the process. Fibronectin, laminin, and
      collagen IV, although increased in absolute amounts, are pushed toward the
      periphery of mesangial areas, in which correlated expression of their
      corresponding beta 1 integrins (alpha 2, alpha 3, and alpha 5, respectively) is
      documented in both LCDD and AL-Am. Deposition of tenascin might be at least
      partially responsible for the perpetuation and irreversibility of the glomerular
      lesion in LCDD.

PMID- 9160317
TI  - Leptomeningeal involvement in chronic lymphocytic leukemia identified by
      polymerase chain reaction in stored slides: a case report.
AB  - The use of polymerase chain reaction (PCR) for routine detection of clonal
      immunoglobulin heavy-chain (IgH) gene rearrangements represents an attractive
      alternative to Southern hybridization analysis not only because PCR protocols are
      quicker and simpler, but also because of the ability to analyze very small
      population of cells in search of minimal residual disease. This can be especially
      important for the detection of clonal malignant cells in locations other than
      bone marrow or peripheral blood. We describe a case in which central nervous
      system involvement, a very rare complication of chronic lymphocytic leukemia, was
      confirmed by PCR analysis for IgH genes rearrangement of the lymphocytes found in
      cerebrospinal fluid. The cerebrospinal fluid and the peripheral blood lymphocytes
      (obtained from archival cytospins stored at the time of diagnosis, 5 years
      before) presented an identical IgH gene rearrangement, as shown by sequence
      analysis. Thus, the use of PCR for IgH genes rearrangement can be very useful in
      the detection of monoclonality in samples with a small number of cells and in the
      confirmation of the common origin of B cells in different specimens of the same
      patient.

PMID- 9160318
TI  - Aggressive gastric peripheral T-cell lymphoma of CD8+ type associated with
      lymphomatous meningitis.
AB  - Most gastric lymphomas are of B-cell origin, and many are either low-grade or
      high-grade B-cell lymphomas of mucosa-associated lymphoid tissue type. Gastric T
      cell lymphomas are very rare, usually of CD4+ type, and few have had genotypic
      studies. We report the case of a gastric peripheral T-cell lymphoma of CD8+ type.
      Genotypic studies demonstrated partial deletion with rearrangement of the T-cell
      receptor beta-chain gene. Lymphomatous meningitis developed, and the patient died
      after only 2 months despite chemotherapy. The case is compared with the other
      gastric T-cell lymphomas that have been reported.

PMID- 9160319
TI  - Spindle epithelial tumor with thymus-like differentiation: a case report with
      cytologic, histologic, immunohistologic, and ultrastructural findings.
AB  - Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare and
      distinctive low-grade neoplasm of thymic or related branchial pouch
      differentiation. The tumor usually presents in the thyroid or lateral neck of
      children and adolescents and could mimic spindle-cell carcinoma, synovial
      sarcoma, or malignant teratoma. We report the clinical, cytologic, histologic,
      immunohistochemical, and ultrastructural features of a SETTLE present for 10
      years in a 15-year-old boy. The fine-needle aspirate, initially interpreted as
      synovial sarcoma, contained numerous clusters of bland spindle cells, with a few
      detached sheets of columnar mucous cells in a homogeneous background of
      dissociated spindle cells. Mitoses, necrosis, and atypia were not present. The
      excised tumor was a well-circumscribed, white-tan mass, with occasional
      microcysts. Microscopically, the mass consisted of a lobulated, highly cellular,
      spindle-cell neoplasm arranged in intersecting, whorled, and storiform fascicles
      separated by fibrous bands. Entrapped within the fibrous bands were squamous
      lined cysts and benign-appearing glands lined by columnar epithelium with goblet
      cells or ciliated pseudostratified epithelium. Immunohistochemically, the spindle
      cells showed diffuse reactivity for cytokeratins, smooth muscle actin, muscle
      specific actin, and MIC-2, and they were negative for epithelial membrane
      antigen, calcitonin, and thyroglobulin. Ultrastructurally, numerous perinuclear
      tonofilaments, some aligned with mature desmosomes, were identified in the
      spindle cells. Occasional cells showed thin filaments with fusiform dense bodies
      occupying the peripheral cytoplasm. These findings distinguish SETTLE from
      ectopic thymoma, synovial sarcoma, medullary carcinoma, and teratoma, and they
      support a thymic epithelial origin for SETTLE, possibly with myoepithelial
      differentiation.

PMID- 9160320
TI  - Cytoplasmic biotin-like activity interferes with immunohistochemical analysis of
      thyroid lesions: a comparison of antigen retrieval methods.
AB  - Cytoplasmic biotin-like activity was identified in formalin-fixed and paraffin
      embedded human thyroid lesions by immunostaining for biotin by use of the
      peroxidase-antiperoxidase method or by peroxidase-labeled streptavidin alone. The
      reactivity of cytoplasmic biotin-like activity was markedly enhanced both by
      pretreatment with trypsin and after heating by autoclaving. Of 208 thyroid
      lesions, 93 showed positive immunostaining for biotin with use of trypsin
      pretreatment. The positive incidence of cases and positive cell ratio were
      highest in papillary carcinoma, followed by follicular carcinoma but lowest in
      the lethal types of thyroid carcinoma: anaplastic carcinoma, squamous cell
      carcinoma and poorly differentiated insular carcinoma. We conclude that
      cytoplasmic biotin-like activity in the common thyroid neoplasms should be
      considered as an interfering factor for immunostaining with avidin-biotin
      combined with selected antigen retrieval methods and with in situ hybridization
      with biotinylated probes.

PMID- 9160321
TI  - Correspondence re: Prevot S, Penna CH, Imbert JC, Wendum D, De Saint Maur PP.
      Solitary fibrous tumor of the adrenal gland. Mod Pathol 1996;9:1170-74.

PMID- 9160322
TI  - Detection of Borrelia burgdorferi DNA by polymerase chain reaction in urine
      specimens of patients with erythema migrans lesions.
AB  - A polymerase chain reaction (PCR) assay was developed for the detection of
      Borrelia burgdorferi-specific DNA in the urine of patients with erythema migrans
      (EM). The target for the PCR was a specific region of the flagellin gene, and DNA
      was extracted from urine by Chelex resin. The detection limit was 1-10 genomes of
      B. burgdorferi, B. garinii or B. afzelii. A prospective study was performed with
      12 consecutively diagnosed patients with EM, to evaluate the PCR assay on
      clinical samples. Borrelia burgdorferi-specific DNA could be detected in urine
      specimens from the 12 patients with EM before antibiotic therapy. Five weeks
      after therapy all the patients were negative by PCR of urine. Results of the
      present study confirm that the described PCR assay is sensitive and that this
      sort of test allows monitoring of the efficacy of therapy in patients with early
      Lyme borreliosis.

PMID- 9160323
TI  - Denaturing gradient gel electrophoresis (DGGE) increases resolution and
      informativity of Alu-directed inter-repeat PCR.
AB  - By inter-repeat PCR, multiple polymorphic loci can be targeted in parallel. To
      improve resolution and extend the number of detectable polymorphisms, Alu
      directed inter-repeat PCR products from two large pedigrees of the Centre d'Etude
      du Polymorphisme Humain (CEPH) were electrophoretically resolved in non
      denaturing polyacrylamide gels and, separately, on the basis of sequence content
      by denaturing gradient gel electrophoresis (DGGE). The resolution in DGGE gels
      was found to be superior to that in non-denaturing gels and a higher number of
      fragments was detected separately. The number of polymorphic bands detected by
      DGGE alone, however, was lower than that after size separation. This is ascribed
      to the fact that because of complete melting, small polymorphic fragments can run
      off the gel. With three Alu-specific primers, 18 and 16 polymorphic bands per
      individual were detected by size separation in pedigrees 1200 and 6600,
      respectively. In the same two pedigrees, seven and 15 polymorphic bands,
      respectively, were detected by DGGE. Segregation analysis of polymorphisms in the
      CEPH pedigrees indicated that most polymorphisms detected by DGGE were different
      from those detected by size separation.

PMID- 9160324
TI  - Development of a sensitive nested PCR method for the specific detection of
      Mycoplasma mycoides subsp. mycoides SC.
AB  - A specific and sensitive test for the detection of Mycoplasma mycoides subsp.
      mycoides small colony type (SC), the aetiological agent of contagious bovine
      pleuropneumonia (CBPP) was developed using two nested PCR reactions. The PCR
      reactions are based on the nucleotide sequence of lipoprotein P72 of M. mycoides
      subsp. mycoides SC. The two specific oligonucleotide primer pairs were chosen to
      match those sequence segments of the P72 gene which differ most from the gene of
      the closely related lipoprotein P67 of Mycoplasma sp. bovine group 7 (strain
      PG50). The nested PCR reacted with all of the 34 different strains of M. mycoides
      subsp. mycoides SC analysed, and gave no amplification product with any of the
      closely related mycoplasmas tested, showing its high specificity. In bronchial
      lavage fluid experimentally contaminated with M. mycoides subsp. mycoides SC, the
      assay was able to detect as few as two viable cells per ml using a simple lysis
      procedure prior to the amplification step. With clinical samples, the sensitivity
      of the nested PCR was about 10(4)-10(5) higher than that of single PCR
      amplifications performed under the same conditions. The assay was also
      successfully used to detect M. mycoides subsp. mycoides SC in bronchial lavage
      fluid of experimentally infected cattle and proved to be more sensitive than
      classical culture methods.

PMID- 9160325
TI  - Acetoxy-acetylaminofluorene-modified dGTP can be used to label oligonucleotides
      or DNA enzymatically.
AB  - A competitive enzyme immunoassay using a bispecific monoclonal antibody (Bi-MAb)
      was developed to quantify acetylaminofluorene (AAF) adducts fixed on DNA and then
      compared to the spectrophotometric method. It was shown that this simple method
      allowed the measurement of as low as 2 pmol per assay of AAF bound to DNA. This
      technique was used to monitor synthesis and purification of N-acetoxy-N-2
      acetylaminofluorene modified dGTP (AAF-dGTP). It was shown that AAF-dGTP can be a
      substrate for the terminal deoxynucleotidyl transferase. Finally, using the Bi
      MAb we developed a non-radioactive sandwich hybridization assay making use of
      oligonucleotide covalently bound to microwells and of synthetic oligonucleotide
      tailed with AAF-dGTP as a probe.

PMID- 9160326
TI  - Geographic variation of the predictive values of genomic mutations associated
      with streptomycin resistance in Mycobacterium tuberculosis.
AB  - Specific mutations associated with resistance to streptomycin (SM) in
      Mycobacterium tuberculosis suggest themselves for its rapid prediction. However,
      as with any diagnostic test, their predictive values are dependent on their
      prevalences. In this report, SM resistance associated mutations in the rrs and
      rpsL genes of 25 SM resistant isolates from Germany and 25 SM resistant isolates
      from Sierra Leone were characterized and compared. Mutations in the rrs gene were
      infrequent in isolates from both localities (20% and 12%, respectively) and thus
      of limited predictive values. In contrast, rpsL mutations were found in 48% of
      the German isolates but only in 24% of the isolates from Sierra Leone. It is
      concluded that the predictive values of mutations in this gene may vary
      significantly with the origin of the samples under investigation.

PMID- 9160327
TI  - Quantitation of parvovirus B19 DNA sequences by competitive PCR: differential
      hybridization of the amplicons and immunoenzymatic detection on microplate.
AB  - A competitive PCR assay was developed to quantify B19 DNA sequences. Target and
      internal standard sequences were co-amplified by the same set of primers. The
      internal standard competitor was constructed by recombinant PCR and differed from
      the original genome sequence in a 21-bp mutagenized fragment, internal to the
      region amplified by the same set of primers. The internal standard competitor was
      cloned in a plasmid vector and the cloned fragment used in all the experiments.
      Target and internal standard sequences were labelled with digoxigenin during the
      co-amplification reaction and the different amplicons were detected in two
      separate hybridization reactions by biotinylated probes specific for the original
      21-bp sequence or the mutagenized one. Hybridized amplicons were captured onto
      streptavidin-oated microtitre wells and detected by anti-digoxigenin antibodies
      conjugated to peroxidase. The chromogenic reaction for peroxidase was
      quantitatively evaluated by optical density determination. The titration curve
      subsequently developed showed a linear relationship over the range 10(2) to 10(5)
      genome copies, thus obtaining an exact quantitative evaluation over a wide range
      together with good sensitivity. Nine reference serum samples positive for B19 DNA
      and eight negative serum samples were tested by the competitive PCR assay for the
      quantitation of B19 DNA sequences.

PMID- 9160328
TI  - In situ hybridization for detection of chicken anaemia virus in peripheral blood
      smears.
AB  - Blood smears, obtained from chickens known to be infected with or free from
      chicken anaemia virus (CAV), were tested to detect CAV DNA by in situ
      hybridization (ISH). A double-stranded, 1485 base-pair (bp) DNA probe was
      prepared employing polymerase chain reaction (PCR). The probe was labelled with
      digoxigenin or biotin by nick translation. In situ hybridization employing simple
      specimen preparation, using both digoxigenin- and biotin-labelled probes,
      provided a rapid and inexpensive method for diagnosis of CAV infection. Infection
      with CAV was detected by ISH prior to seroconversion by indirect
      immunofluorescence assay.

PMID- 9160329
TI  - The potential of 5' nuclease PCR for detecting a single-base polymorphism in
      Orthopoxvirus.
AB  - A fluorogenic 5' nuclease PCR assay was evaluated for its ability to specifically
      detect and differentiate DNA of two Orthopoxvirus species. A pair of consensus
      primers that target a DNA segment of the Orthopoxvirus haemagglutinin gene, and
      two oligonucleotide probes; each labelled with a different fluorescent reporter
      dye and the same quencher dye, were used in a single-tube assay. The assay is
      based on the 5'-->3' nuclease activity of AmpliTaq DNA polymerase that cleaves a
      fluorescein-labelled hybridized probe. Probe cleavage generates specific
      fluorescent signals whose intensity can be quantified by fluorometry. After
      evaluating the effects of various annealing temperatures and probe concentrations
      and normalizing the emission intensities of the reporter dyes, it was possible to
      detect and differentiate monkeypox and vaccinia virus DNAs on the basis of a
      single-base polymorphism. The sensitivity of the 5' nuclease PCR assay is
      comparable to the sensitivity of ethidium bromide-stained gels, but the assay
      provides higher specificity and virtually eliminates the need for laborious post
      PCR processing.

PMID- 9160330
TI  - Rapid PCR-based delineation of the porcine nodular worms, Oesophagostomum
      dentatum and O. quadrispinulatum.
AB  - At some stages of development, it is impossible to identify the porcine nodular
      worms Oesophagostomum dentatum and O. quadrispinulatum to the species level using
      morphological parameters. A molecular approach utilizing genetic markers in the
      second internal transcribed spacer (ITS-2) of ribosomal (r) DNA was developed to
      overcome this limitation. The ITS-2 sequence of each species was determined, and
      specific oligonucleotide primers were designed to regions of greatest sequence
      difference between the species. Utilizing these primers, rapid PCR procedures
      were developed for the specific amplification of DNA of O. dentatum or O.
      quadrispinulatum, which are now used routinely to monitor the purity of larval
      cultures and to confirm the identity of larvae derived from the intestine or
      faeces. The application of specific PCR has major implications for studying the
      population biology of nodular worms in the pig model.

PMID- 9160331
TI  - Detection of mutations in human genes by a new rapid method: cleavage fragment
      length polymorphism analysis (CFLPA).
AB  - Cleavage fragment length polymorphism analysis with silver staining visualization
      (CFLPA-SS) was used for the detection of mutations previously detected by single
      strand conformation (SSCA) or heteroduplex analyses (HA); in order to assess this
      new method for mutation screening. The analysed mutations include single
      nucleotide transitions, transversions, a deletion and a duplication in the
      following genes: CFTR (cystic fibrosis transmembrane conductance regulator),
      COL4A5 (collagen type 4 alpha 5 chain), PKD1 (polycystic kidney disease 1), and
      FGFR3 (fibroblast growth factor receptor 3). Peripheral blood leukocyte genomic
      DNA was isolated, amplified by polymerase chain reaction (PCR), and then cleaved
      by Cleavase I enzyme at different temperatures. Electrophoresis of the fragments
      on denaturing polyacrylamide gel was followed by silver staining for 1 min. All
      13 mutations investigated were reproducibly detected. CFLPA-SS proved to be a
      reliable method for mutation detection and more rapid than SSCA and HA.

PMID- 9160332
TI  - A new polymorphism in exon 14 of the dystrophin gene detected by RT-PCR and DGGE.

PMID- 9160333
TI  - Racial differences in polymorphic allele heterozygosities of the human hepatic
      triglyceride lipase gene.

PMID- 9160334
TI  - Postulate for the molecular mechanism of the vacuolar H(+)-ATPase (hypothesis).

PMID- 9160335
TI  - Drug-induced transmembrane lipid scrambling in erythrocytes and in liposomes
      requires the presence of polyanionic phospholipids.
AB  - The asymmetric transmembrane distribution of phospholipids between the two
      bilayer halves of erythrocyte can be modified upon addition of cationic
      amphiphilic drugs, such as chlorpromazine or verapamil. We studied this
      phenomenon in erythrocytes and in lipid vesicles using spin-labelled analogues of
      the endogenous phospholipids. The extent of the rapid disappearance of the
      analogues from the erythrocyte outer leaflet depended on the concentration of the
      drug. Up to 40% of spin-labelled sphingomyelin moved to the inner erythrocyte
      leaflet in 10 min in the presence of 1.5 mm chlorpromazine. Verapamil or
      vinblastine gave similar results. On the other hand, the inside-outside movement
      of the aminophospholipid analogues was less evident, and did not exceed 10%. This
      apparent discrepancy between inward and outward movements could result from the
      formation of an endovesicle which is known to occur upon drug addition at high
      concentration. A fraction of lipids would be trapped in the intravesicular
      leaflet, corresponding to the cell outer leaflet, and be inaccessible both from
      the cytoplasm and the extracellular medium. In cells submitted to a metabolic
      depletion of cellular ATP the intensity of the scrambling induced by the
      amphipaths was drastically lowered. We attribute this effect to the important
      reduction of the membrane content in phosphatidylinositol-4,5-bisphosphate
      (PIP2). The involvement of the latter lipid in triggering scrambling was partly
      confirmed by experiments carried out with artificial membranes. Indeed, in large
      unilamellar vesicles PIP2 is required in order to obtain a rapid redistribution
      of phospholipids between the two leaflets upon addition of drugs. However, the
      extent of phospholipid redistribution was limited to 15-20%. This redistribution
      was also induced when the vesicle membrane contained di-anionic phospholipids
      (phosphatidylinositol-4-monophosphate or diphosphatidylglycerol), but did not
      occur when it contained mono-anionic phospholipids (phosphatidylserine or
      phosphatidylinositol). Some drugs such as methochlorpromazine, active in
      artificial membranes, were ineffective in erythrocyte membranes, probably because
      they could not cross the membrane and reach PIP2 molecules at the cytoplasmic
      leaflet.

PMID- 9160336
TI  - Channel activity caused by a Bacillus thuringiensis delta-endotoxin preparation
      depends on the method of activation.
AB  - The spontaneous insertion of Bacillus thuringiensis Cry delta-endotoxins into
      planar lipid bilayers to form discrete channels in the absence of receptors is
      the subject of conflicting reports in the literature. Because these proteins are
      synthesized as protoxins requiring proteolytic activation for conversion to the
      active form, differences in the in-vitro protocol used for this activation could
      be responsible for the contradictory results. To investigate this, CrylA(c) toxin
      was activated by different procedures, and its ability to release glucose
      entrapped within liposomes and to form channels in planar lipid bilayers
      assessed. The toxin preparations exhibited widely differing activities on the
      lipid membranes; SDS-PAGE and immunoblot analysis suggested that variations in
      the protein profile of the activated samples could be responsible. These findings
      raise important practical considerations for further in-vitro studies into the
      mechanism of action of these toxins.

PMID- 9160337
TI  - Fluorescence spectroscopic study of the interaction of saporin with phospholipid
      vesicles.
AB  - Saporin-S6 (SO-6) is a type-1 ribosome-inactivating protein purified from the
      seeds of Saponaria officinalis. The fluorescence characteristics of SO-6 were
      studied in the presence and absence of phospholipids. The interaction of SO-6
      with DMPG or DMPC vesicles results in a decrease in the fluorescence emission
      intensity of tryptophan without any shift in the emission maximal wavelength. The
      results of fluorescence titration indicate that DMPG/SO-6 saturation molar ratio
      is 100: 1, but the binding of DMPC with SO-6 does not reach a saturating plot. A
      shielding of the tryptophan fluorescence from quenching by acrylamide on
      interaction with the phospholipids was observed, and this shielding was more
      pronounced in the presence of DMPG. The interaction of SO-6 with DMPG vesicles is
      stronger in the liquid-crystalline phase than in the gel phase. Extrinsic
      fluorescence studies indicated that the interaction of the protein with DMPG
      vesicles does not modify the phase transition temperature of the lipid, but
      decreases the amplitude of the change of fluorescence anisotropy associated with
      the co-operative melting of 1,6-diphenyl-1,3,5-hexatriene (DPH)-labelled
      vesicles. These results indicate that both electrostatic and hydrophobic
      components are involved in the SO-6-lipid vesicle interaction.

PMID- 9160338
TI  - Mutual modulation of sphingomyelinase and phospholipase A2 activities against
      mixed lipid monolayers by their lipid intermediates and glycosphingolipids.
AB  - Sphingomyelinase activity against pure sphingomyelin monolayers is constant up to
      a surface pressure of 18 mN/m and falls above it. Sphingomyelinase- and
      phospholipase A2-mediated phosphohydrolytic pathways are mutually modulated by
      the presence of their respective substrates and products. At 15 mN/m non
      substrate lipids such as ceramide at a mole fraction of 0.1 in mixed films with
      the pure substrate, inhibit the sphingomyelinase activity. Ganglioside GM1,
      another ceramide-containing complex sphingolipid, also inhibits sphingomyelinase
      activity, while a chemically related glycosphingolipid such as asialo-GM1 has no
      effect. The activity is unaltered by dipalmitoylphosphatidylcholine and by an
      equimolar mixture of its products of hydrolysis by phospholipase A2, fatty acid
      and lysoderivative, but it is inhibited by only one of them or by
      dilauroylphosphatidylcholine. Phospholipase A2 is inhibited by sphingomyelin, and
      activated by ceramide and by palmitic acid, one of the products of its own
      phosphohydrolytic reaction.

PMID- 9160339
TI  - Comparative study of the fluidity of plasma and disc membranes of bovine rod
      outer segments by electron-spin resonance.
AB  - The fluidity of isolated plasma and disc membranes from bovine rod outer segments
      has been compared by electron-spin resonance spectroscopy using the stearic acid
      spin labels 5-SASL and 16-SASL. This comparison is of interest, given the fact
      that the disc membranes arise by invagination from the plasma membrane. Analysis
      of the order parameter in the hydrophilic part of the membrane, and of rotational
      correlation time in the hydrophobic part, showed a difference of fluidity between
      these two types of membranes, with a higher fluidity in the disc membranes in
      both their hydrophilic and hydrophobic regions. For example, at a temperature of
      37 degrees C, plasma and disc membranes exhibited values of 0.64 and 0.61 for the
      order parameter (S), and 9.1 and 14.5 s-1 for the rotational correlation
      frequency (v), respectively. These findings are discussed in relation to
      previously described differences in the biochemical compositions of the
      membranes.

PMID- 9160340
TI  - On the accessibility of phosphatidylglycerol to periodate in Escherichia coli.
AB  - The transverse distribution of phosphatidylglycerol (PG) across the inner
      membrane of Escherichia coli was studied. The oxidation of PG by periodate was
      used to discriminate between the PG present in the cytoplasmic and in the
      periplasmic leaflet of the inner membrane. Applied to large unilamellar vesicles
      derived of an E. coli lipid extract, the periodate method demonstrated the
      expected symmetrical distribution of PG over the bilayer. However, both in right
      side-out and in inside-out inner membrane vesicles isolated from E. coli, as well
      as in intact E. coli cells, the entire pool of PG was oxidized by periodate. The
      oxidation reaction proceeded at such a high rate that it was impossible to
      determine the distribution of PG across the membrane. Apparently, periodate
      easily permeates through the membrane. This permeation could not be inhibited or
      slowed down, and it was concluded that the use of periodate as oxidizer of PG is
      not a suitable method to determine the transverse distribution of this
      phospholipid in the Gram-negative bacterium E. coli. However, periodate can be
      used to selectively modify the total PG pool in this organism.

PMID- 9160341
TI  - Ingested IFN-alpha has biological effects in humans with relapsing-remitting
      multiple sclerosis.
AB  - Parenterally administered human recombinant type I interferons (hrIFN) in
      relapsing-remitting multiple sclerosis (RRMS) decrease relapses and spontaneous
      in vitro IFN-gamma production, reduce clinical progression, and decrease magnetic
      resonance imaging (MRI)-defined disease activity and lesions. Parenterally
      administered type I IFN use is limited by clinical and chemical toxicities, and
      the induction of antibodies that abrogate their activity in vivo correlated with
      the loss of clinical benefit. Therefore, we determined whether ingested IFN-alpha
      was non-toxic and had biological effects in humans. Ingested hrIFN-alpha showed
      no toxicity in normal volunteers or patients with RRMS at doses ranging from 300
      to 100,000 units. In subjects with RRMS, a significant decrease in Con A-mediated
      proliferation and serum soluble intercellular adhesion molecule-1 (sICAM-1), a
      surrogate measure for disease activity in MS, was found after ingesting 10,000
      and 30,000 units IFN-alpha The RRMS subjects also showed decreased IL-2 secretion
      after ingesting 10,000 units IFN-alpha and decreased IFN-gamma, TGF-beta and IL
      10 production after ingesting 30,000 units IFN-alpha. The decreased secretion of
      IFN-gamma and IL-2 by ingested IFN-alpha suggests that oral IFN-alpha may cause a
      functional inhibition of Th J-like T helper cells in RRMS, a potential site of
      intervention at the level of effector T cells in MS. Our studies support the oral
      use of human IFN-alpha as a biological response modifier in humans.

PMID- 9160342
TI  - Positron emission tomography, magnetic resonance imaging and proton NMR
      spectroscopy of white matter in multiple sclerosis.
AB  - OBJECTIVE: To assess characteristics of MS lesions and normal appearing white
      matter (NAWM) with various imaging modalities. Glucose metabolism was
      investigated with FDG-PET, metabolite concentration with proton NMR spectroscopy,
      and lesion detection with routine brain MRI. METHODS: Thirteen patients were
      studied in a stable phase of their disease, and two during an acute episode. Nine
      healthy volunteers served as controls. RESULTS: Three patients had a normal brain
      MRI, 12 had typical lesions. MR images were registered to the PET planes. Lesions
      and contra-lateral control areas were analyzed, 10/15 lesions showed relative
      hyper-metabolism and 2 hypo-metabolism. NAA concentration was significantly
      decreased in both lesions and NAWM. CONCLUSION: In stable MS, most large lesions
      have a relatively increased glucose utilization and decreased NAA concentration.
      NAWM showed a significantly decreased NAA concentration compared to healthy
      subjects, but no difference in glucose metabolism. Active lesions in acute MS are
      also hyper-metabolic. This finding opens a new window on the classification of
      white matter lesions based on glucose utilization.

PMID- 9160343
TI  - Long-lasting depression of soleus motoneurons excitability following repetitive
      magnetic stimuli of the spinal cord in multiple sclerosis patients.
AB  - The effect of repetitive magnetic stimulation at the spinal level on the soleus H
      reflex amplitude was evaluated in II MS patients with lower limb spasticity and
      in nine healthy subjects. In MS patients stimulation with a train of 16 stimuli
      at 25 Hz induced a decrease in amplitude to 61.2 +/- 25.7% of the unconditioned H
      reflex amplitude at interstimulus interval (ISI) of 10-1000 ms (P < 0.01). The
      amount of decrease in H-reflex amplitude was highly dependent on the stimulation
      intensity and the placement of the coil, and to a lesser extent influenced by the
      stimulation frequency. No decrease in motor evoked potentials (MEPs) evoked by
      transcranial magnetic stimulation was seen following trains of 16 stimuli at mid
      thoracic in contrast to the post-stimulation depression in H-reflex amplitude
      which could imply that mechanisms acting at presynaptic level were involved. In
      response to repetitive magnetic stimuli for 5 min, a long-lasting decrease in H
      reflex amplitude to a level of about 70% of the pre-stimulation H-reflex
      amplitude occurred in MS patients (P < 0.01). A similar although not significant
      decrease was observed in healthy subjects. We propose that long-lasting
      depression of the soleus H-reflex amplitude after repetitive magnetic stimuli is
      due to long-term depression of the synaptic transmission.

PMID- 9160344
TI  - The MS Impairment Scale: a pragmatic approach to the assessment of impairment in
      patients with multiple sclerosis.
AB  - We developed a measurement scale for assessment of impairment in MS patients
      (MSIS) in accordance with the recommendations of WHO. The items were kept close
      to a standard neurologic examination, and a short battery of cognitive tests was
      added. Normality was assigned to the value, zero, and the theoretical maximum
      score was 204. Two-hundred and ten multiple sclerosis (MS) patients were rated by
      one neurologist on the MS impairment Scale (MSIS), the Extended Disability Status
      Scale (EDSS), and the Ambulation Index (AI). The median MSIS score was 52 (5
      147), the median EDSS 6.5 (1-9.5), and the median AI 5 (1-5). The relation
      between the MSIS scores and the EDSS was best described by an exponential
      function (non-linear regression coefficient, R = 0.87). Sixty-two of the patients
      were reexamined and rated by another neurologist. The interrater reliability
      coefficient (R) of the MSIS was 0.95, of the EDSS 0.91, and of the AI 0.94. Forty
      patients were examined twice by the first neurologist. The intrarater reliability
      coefficient was 0.97 for the MSIS, 0.95 for the EDSS, and 0.98 for the AI. The
      MSIS is easy to use and is robust to observer dissimilarities. It has a monomodal
      univariate distribution and has a better discriminatory power than the EDSS,
      especially in the EDSS range 6-9, while the interrater reliability of the MSIS is
      at least as good as that of the EDSS and the AI.

PMID- 9160345
TI  - Multiple sclerosis in childhood: clinical features of 149 cases.
AB  - From the retrospective study of 3375 patients affected by clinically definite or
      probable multiple sclerosis (MS), 149 patients were collected with onset of the
      disease before the age of 16 years (4.4%). Female/male ratio was higher than that
      of the adult onset MS (AOMS) population (2.2 vs 1.6) particularly at ages of
      onset after 12 years (3.0, P = 0.007 vs AOMS). Among initial symptoms, those
      suggesting brainstem dysfunction (25%) were more frequent compared to other
      systems and compared to AOMs symptoms; motor and sensory disturbances were
      slightly less frequent (respectively 17.5% and 18.3%). Optic neuritis appeared in
      16.5% of cases with onset in childhood and in 16.2% of cases with AOMS,
      cerebellar disturbances respectively in 9.1% and 7.7%. The first interattack
      interval and the clinical course of early onset MS did not differ significantly
      from AOMS. In early onset MS patients with disease duration < 8 years, cases with
      EDSS > 6 were slightly more frequent than in the AOMS group (P = 0.04). The
      frequency of cases for different levels of disability was similar for disease
      duration > 8 years.

PMID- 9160346
TI  - [Opioid receptor types and dependence].
AB  - The existence of mu, delta and kappa opioid receptors in the central nervous
      system is well documented. The present review focuses on the relationships
      between opioid receptor types and physical and psychic dependences. Mu and delta,
      but not kappa opioid receptor agonists produce physical dependence. From
      behavioral, biochemical and molecular biological studies, it is suggested so far
      that development of physical dependence on morphine results predominantly from an
      activation of mu 1 and mu 2 opioid receptors which causes functional changes in
      Gi/o, adenylate cyclase, protein kinases A and C, beta-adrenoceptor and NMDA
      receptor in the locus coeruleus. Recently, there have been significant advances
      in studies on psychic dependence. Mu and delta opioid receptor agonists produce
      psychic dependence, but kappa opioid receptor agonists rather produce an aversive
      effect. Activation of the mesolimbic dopamine system may lead to psychic
      dependence on opioids. Mu and delta 1 opioid receptor agonists activate the
      mesolimbic dopamine system to induce a rewarding effect, whereas the rewarding
      effect of delta 2 opioid receptor agonists may be produced through a non
      dopaminergic system. There are complicated interactions among opioid receptor
      types. The activation of kappa opioid receptor suppresses physical and psychic
      dependences on mu and delta opioid receptor agonists, but the activation of delta
      opioid receptor potentiates the dependence on mu opioid receptor agonists. The
      clinical use of morphine in patients with cancer pain won't develop dependence
      probably due to the balance of the opioid system coming from these interactions.

PMID- 9160347
TI  - [A novel photochemical model of the middle cerebral artery for thrombosis
      research and evaluation of anti-thrombotic agents].
AB  - We have established a novel thrombosis model of the middle cerebral artery (MCA).
      The thrombotic occlusion of the MCA was induced by the photochemical reaction
      between Rose Bengal and green light, which causes endothelial injury followed by
      platelet adhesion, aggregation and formation of a platelet and fibrin-rich
      thrombus at the site of the photochemical reaction. With this model, we have
      investigated the effects of anti-thrombotic agents, thrombolytic agents and
      neuroprotective agents. In our model, ADP, thromboxane A2 (TXA2) and thrombin
      play a key role in thrombus formation of the MCA. Tissue-type plasminogen
      activator (tPA) could cause an opening of the thrombotic MCA occlusion and
      reduced the size of the cerebral infarction. Furthermore, a TXA2 antagonist
      enhanced the thrombolytic efficacy of tPA. MS-153 ((R)-(-)-5-methyl-1-nicotinoyl
      2-pyrazoline), a glutamate release inhibitor and YM90K [6-(1 H-imidazol-1-yl)-7
      nitro-2,3(1H, 4H)-qunoxalinedione monohydrochloride, an alpha-amino-3hydroxy
      5methyl-4-isoxazole (AMPA) antagonist reduced the cerebral infarction 24 hr after
      the MCA occlusion. This model is very useful for investigating the mechanisms of
      anti-thrombotic and neuroprotective agents and evaluating the effects of these
      agents.

PMID- 9160348
TI  - [Specific regulation of gene expression in brain by antisense
      oligodeoxynucleotides].
AB  - The synthetic oligodeoxynucleotide (ODN) complementary to the normal (sense)
      mRNA, so-called antisense ODN, has been used to regulate the gene expression in
      the brain. It has been reported to interfere with transcription, pre-mRNA
      splicing and translation through at least two mechanisms; i.e., its competition
      with transcription and protein synthesis machinery or induction of mRNA cleavage.
      The unmodified antisense ODN was shown to be the RNase activator when it
      hybridizes with at least four contiguous bases of mRNA. In contrast, the
      phosphorothioate ODN (S-ODN) is reported to be a less effective activator of RNas
      II and more resistant to the nuclease attack than unmodified ODN. Because of
      these properties, S-ODNs are preferentially employed in antisense ODN
      experiments. When the DNA sequence of the target gene is determined, we can
      design an antisense ODN that selectively hybridizes with the bases of a nucleic
      acid (DNA or RNA) related to the target gene. The initial sites of specific
      binding of most drugs are known to be proteins such as receptors and enzymes.
      Therefore, the specific modulation of target protein synthesis by the antisense
      ODN method is quite interesting to the pharmacologist. We have studied the change
      in the morphine-induced behaviors after the microinjection of antisense S-ODN
      directed against the m-opioid receptor (MOR) into the periaqueductal gray (PAG)
      or lateral ventricle of rat brain. We could detect the decrease of the MOR mRNA
      level in PAG by the RT-PCR method and that in whole brain by the Northern blot
      technique. Although the antisense ODN method seems to be quite useful for the
      modulation of a given gene expression, many problems still remain to be
      elucidated. These include the mechanism of the regulation of a target gene,
      pharmacokinetics of antisense ODN and toxicity of antisense ODN.

PMID- 9160349
TI  - [Antiallergic effects of a novel compound, SWR-00151].
AB  - The effects of a newly synthesized compound, SWR-00151 (4-[2-[4-(1H-indol-3-yl)-1
      piperidinyl)ethyl]-2(1H)-quinolinone), on experimental Type I allergic models
      were investigated. Results obtained were as follows: The compound (3
      approximately 30 mg/kg, p.o.) dose-dependently inhibited 48-hr passive cutaneous
      anaphylaxis (PCA) in the rat. From the strong antagonism against the histamine
      induced contraction of the isolated guinea pig ileum and the lack of suppressive
      effect on anaphylactic histamine release from rat peritoneal exudate cells, it is
      deduced that the compound's inhibitory action against PCA is due to
      antihistaminic action. Both gamma 1-rich serum- and IgE-rich serum-mediated
      experimental asthmas in the guinea pig were also considerably inhibited by a
      small dose (1 mg/kg, p.o.) of the compound. The inhibitory mechanism seems to be
      almost the same as that of the PCA because the compound did not show any effect
      on the experimental asthma in guinea pigs pretreated with H1- and H2
      antihistaminics. In addition to that, it is well known that the model is largely
      mediated by anaphylactically released histamine. On the other hand, while
      ketotifen and oxatomide, which possess potent antihistaminic activity, modestly
      suppressed a rat experimental asthma SWR-00151 still demonstrated a substantial
      inhibitory activity, strongly suggesting that histamine does not play an
      important role in this asthma model. Serotonin was revealed to be partly
      responsible for the early phase of the reaction by the assessment with
      methysergide, an antiserotonergic, and SWR-00151 as well as oxatomide and
      ketotifen showed slight antagonism against serotonin in high concentrations (10(
      6) and 10(-5) M) in vitro. When thromboxane (TX) B2 in the plasma was measured
      during the reaction, significant increased levels of the chemical mediator were
      found, which were obviously prevented by the treatment with SRW-00151. From these
      results, SWR-00151 is expected to be a drug effective for the treatment of asthma
      through mechanisms not only of antihistaminic action but also through inhibition
      of anaphylactic formation/release of other mediators like TXA2.

PMID- 9160350
TI  - Methionine dependence of tumor cells: programmed cell survival?
AB  - A majority of tumor cell lines are considered to be "methionine-dependent"
      because of their inability to grow in culture when methionine is replaced by its
      precursor, homocysteine. We have previously shown that this phenotype is not due
      to the incapacity to synthesize methionine from homocysteine but rather to a
      deficiency in the "methionine salvage pathway", including 4-methylthio-2
      oxobutanoic acid (MTOB), which is transaminated into methionine. At low
      concentrations MTOB can restore normal growth of methionine-dependent cell lines
      in the absence of methionine. However, when MTOB concentrations are increased the
      cells undergo apoptosis. Methional, a metabolite of MTOB produced by the branched
      chain oxo acid dehydrogenase complex, is a potent inducer of apoptosis in a
      murine lymphoid cell line. We suggest that the methionine-dependent phenotype is
      associated with a reduced content of methional, which behaves as a proapoptotic
      agent. For this reason, methionine-dependent cells have a relative survival
      advantage.

PMID- 9160351
TI  - Effects of estradiol on the expression and production of IGFBP-2 by R3230AC
      mammary tumor cells.
AB  - The R3230AC mammary adenocarcinoma of the Fischer rat possesses Type I and Type
      II IGF receptors. The mRNAs for IGFBP-2, -3, -4, -5 and -6 have been recently
      identified in this tumor in vivo and in vitro. Using western blotting techniques
      on tumor tissue homogenates or conditioned media, we demonstrated that IGFBP-2
      and, to a lesser extent, IGFBP-3 were expressed, produced, and secreted by the
      R3230AC tumor cells. Moreover, immunohistochemical assessment of tumor sections
      with anti-IGFBP-2 demonstrated that signal for IGFBP-2 was localized in the
      neoplastic glandular epithelium and often in the lumina of the pseudoglandular
      structures characteristic of this neoplasm. Expression of IGFBP-2 is regulated by
      the estrogen status of the host. The significant increase occurring in tumors
      from ovariectomized hosts was completely reversed with hormone repletion. Both
      mRNA expression and production of IGFBP-2 in vitro were also regulatable by the
      presence of estradiol-17 beta, with both processes being inhibited by its
      addition to the cell culture medium. Thus, the response of IGFBP-2 to estrogen
      showed agreement both in vivo and in vitro, whereas progesterone had no
      significant effect on these parameters. In the R3230AC tumor, estrogen treatment
      in vivo decreases tumor growth. Therefore, a relationship could exist between the
      action of estradiol to inhibit production of IGFBP-2 and the ability of estrogens
      to regulate tumor growth.

PMID- 9160352
TI  - Evaluation of TNF-alpha effects on radiation efficacy in a human lung
      adenocarcinoma model.
AB  - This study sought to determine if pretreatment with low-dose tumor necrosis
      factor-alpha (TNF-alpha) can enhance the effects of radiation in an NCI-H441
      human lung tumor xenograft model. In vitro assays were performed on spleen cells,
      blood leukocytes, and plasma from the animals, as well as on cultured tumor
      cells. Tumors in animals given only TNF-alpha grew as well as, or better than,
      tumors in their untreated counterparts at all time-dose regimens employed. In
      contrast, early treatment with a total radiation dose of 16 Gy resulted in
      complete tumor inhibition, whereas 8 Gy modestly (but significantly, P < 0.05)
      slowed tumor progression. However, the administration of TNF-alpha (4 x 10(4)
      total units/mouse) 16-18 h prior to irradiation (8 Gy total dose) enhanced the
      antitumor effects of radiation when treatment was initiated early (P < 0.05).
      Oxygen radical production and response to mitogenic stimulation by splenocytes
      were greatest in untreated tumor-bearing animals. Total leukocyte counts in mice
      given radiation or TNF-alpha + radiation were low, and treatment-related changes
      were found in percentages of neutrophils and lymphocytes. In vitro assays of
      tumor cells showed that TNF-alpha + radiation resulted in greater suppression of
      clonogenic survival and incorporation of [3H]TdR and [3H]UdR incorporation than
      either agent alone. These results suggest that the use of low-dose TNF-alpha
      together with radiation may be beneficial in the clinical setting and so warrant
      further investigation.

PMID- 9160353
TI  - Involvement of a CrmA-insensitive ICE/Ced-3-like protease in ceramide-induced
      apoptosis.
AB  - Ceramide has emerged as a novel lipid mediator of tumor necrosis factor (TNF)
      induced apoptosis. However, the signals involved in this response are unknown.
      The present study demonstrates that ceramide-induced internucleosomal DNA
      cleavage is temporally associated with proteolytic cleavage of poly(ADP-ribose)
      polymerase (PARP) and protein kinase C (PKC) delta. Overexpression of baculovirus
      protein p35 blocked ceramide-induced DNA fragmentation and proteolytic activity,
      whereas overexpression of cowpox virus protein CrmA had no effect on these
      events. By contrast, TNF-induced DNA cleavage and proteolytic activity was
      inhibited by CrmA as well as p35. These results indicate that ceramide-induced
      apoptosis involves the activation of a CrmA-insensitive protease that is distinct
      from that induced by TNF.

PMID- 9160354
TI  - Inhibition by galloylglucose (GG6-10) of tumor invasion through extracellular
      matrix and gelatinase-mediated degradation of type IV collagens by metastatic
      tumor cells.
AB  - Tumor invasion into extracellular matrix (ECM) and basement membrane (BM) is a
      crucial step in the complex multistage process that leads to metastasis
      formation. GG6-10 galloylglucose, isolated from Galla Rhois, inhibited the
      invasion of metastatic HT-1080 cells into a reconstituted BM, such as a
      Matrigel/fibronectin (FN)-coated filter, in a concentration-dependent fashion.
      GG6-10 affected neither the tumor cell adhesion and haptotactic migration to ECM
      components (Matrigel and FN), nor the growth of HT-1080 cells. The gelatin
      zymography revealed that GG6-10 was able to inhibit not only the degradation of
      gelatin mediated by matrix metalloproteinases (MMP)-2 and -9 in conditioned
      medium of HT-1080 tumor cells but also the production of MMP from the tumor cells
      in a concentration-dependent manner. MMP production is well known to be
      positively regulated by various cytokines, such as tumor necrosis factor-alpha
      (TNF-alpha). Thus, we examined the effect of GG6-10 on the TNF-alpha-mediated
      translation of the MMP-9 gene using HT-1080 cells transfected with the MMP-9
      promoter linked to the luciferase gene as a reporter. Similarly to prednisolone,
      GG6-10 was found to inhibit the TNF-alpha-inducible promoter activity. In keeping
      with these results, GG6-10 might inhibit tumor cell invasion by inhibiting the
      gelatinolysis mediated by MMP-2 and -9 and interfering with the production of MMP
      via inhibiting transcription of the promoter for MMP.

PMID- 9160355
TI  - Lisofylline as a modifier of radiation therapy.
AB  - Lisofylline is a new methylxanthine. The potential of lisofylline to enhance the
      response to ionizing radiation of the EMT-6 murine mammary carcinoma in vitro and
      in vivo was assessed and compared with pentoxifylline. Addition of lisofylline
      (100 microM) or pentoxifylline (100 microM) from the time of radiation exposure
      and throughout the time of colony formation did not alter the response of
      normally oxygenated EMT-6 cells to gamma-radiation delivered at 0.76 Gy/min or
      12.3 Gy/min. The dose modifying factor for hypoxic EMT-6 cells by lisofylline or
      pentoxifylline and radiation delivered at 0.76 Gy/min was 2.3. Higher dose rate
      radiation (12.3 Gy/min) was more cytotoxic toward hypoxic EMT-6 cells than lower
      dose rate radiation. The dose modifying factor produced by lisofylline in the
      high dose rate radiation setting was 1.2. In vivo, using the tumor cell survival
      assay, lisofylline decreased the shoulder of the radiation survival curve (0.76
      Gy/min) by a factor of 1.7 +/- 0.2 while pentoxifylline did not. In the tumor
      growth delay assay, administration of multiple doses of lisofylline or
      pentoxifylline along with single dose radiation (0.76 Gy/min) was 1.3, while the
      radiation dose modifying factor for lisofylline or pentoxifylline administered by
      continuous infusion was 1.5. Overall, lisofylline was a more effective modifier
      of gamma-radiation therapy than pentoxifylline, and further investigation of
      lisofylline in this setting is warranted.

PMID- 9160357
TI  - Reference listings in cancer research.

PMID- 9160356
TI  - Systemic chemotherapy alters interleukin-1 beta and its receptor antagonist
      production by human alveolar macrophages in lung cancer patients.
AB  - The purpose of this study was to determine whether cytotoxic chemotherapy
      influences the number and function of alveolar macrophages (AM) in patients with
      lung cancer. AM were obtained by bronchoalveolar lavage from 24 patients with
      lung cancer and 17 control patients. The functional integrity of AM was
      determined by their ability to produce interleukin-1 beta (IL-1 beta) and
      interleukin-1 receptor antagonist (IL-1ra) before and after platinum-containing
      systemic chemotherapy. The productions of IL-1 beta and IL-1ra were quantitated
      by enzyme immunoassays. The proportions of multinucleated cells among AM were
      significantly decreased after systemic chemotherapy in lung cancer patients. No
      significant difference in spontaneous and lipopolysaccharide (LPS)-stimulated IL
      1 beta or IL-1ra production by AM was observed between lung cancer patients and
      control patients. Significant increase of IL-1 beta and significant decrease of
      IL-1ra production by AM were demonstrated in patients with small cell lung cancer
      who experienced response to systemic chemotherapy. These results suggest that
      systemic chemotherapy may influence functional roles of AM in the lung, and
      consideration of influence of systemic chemotherapy on host functions is
      important in cancer treatment.

PMID- 9160358
TI  - Extracorporeal circulation for port-access cardiac surgery.
AB  - Minimally invasive techniques for cardiac surgery are a new approach in
      performing some cardiac operations. Minimally invasive surgery may minimize
      patient discomfort, length of stay in the hospital and postoperative
      rehabilitation. These procedures utilize a small thoracotomy for direct
      visualization of the heart. However, without the use of cardiopulmonary bypass,
      this approach is limited to some epicardial procedures such as coronary bypass
      grafting, where the heart rate is pharmacologically reduced. Port-access cardiac
      surgery is a new approach which provides all the benefits of minimally invasive
      surgery without sacrificing the advantages of cardiopulmonary bypass and
      myocardial preservation. Port-access cardiac surgery uses an anterior
      mediastinotomy and thoracic ports in conjunction with a specially designed set of
      endovascular catheters. These catheters provide a mode to arrest, preserve and
      vent the heart through an endoaortic occlusion balloon positioned in the
      ascending aorta. A pulmonary artery vent and coronary sinus cardioplegia catheter
      can also be used. These endovascular catheters, integrated with a modified heart
      lung machine, provide complete cardiopulmonary support through extrathoracic
      cannulae inserted in a femoral artery and vein. Maintenance and monitoring of
      this endovascular cardiopulmonary bypass system requires the use of a kinetic
      pump in the venous drainage line to augment return to the heart-lung machine.
      Special guidelines and management parameters exist to optimize bypass with this
      catheter system. Using this system, port-access, minimally invasive surgery can
      be applied to a wider range of both epicardial and intracardiac procedures.

PMID- 9160359
TI  - Prolonged extracorporeal life support for bridging to transplant: technical and
      mechanical considerations.
AB  - Through July 1995, the Extracorporeal Life Support Organization (ELSO) registry
      listed 87 patients who received extracorporeal life support (ECLS) as a bridge to
      cardiac transplantation with a survival rate of 41%. At Arkansas Children's
      Hospital, 17 patients (aged between two days and 24 years) with diagnoses of
      dilated cardiomyopathy (seven), postcardiotomy (seven) and acute viral
      myocarditis (three) were bridged with ECLS. Mechanical complications only
      occurred in two patients, neither of which necessitated withdrawal of ECLS.
      Decompression of the left heart was performed in 11 patients, six via a
      surgically placed vent and five with a blade/balloon artial septostomy.
      Documented infection occurred in 11/17 patients, but only one patient died from
      infection. Fifteen of 17 patients (88%) recovered or were transplanted, of which
      13 (76%) were discharged home. With left-heart decompression and appropriate
      treatment of infection, ECLS may be used as a bridge to cardiac transplantation
      or until the return of cardiac function.

PMID- 9160360
TI  - The effect of protamine on the epicardial microflow and the graft flow in open
      heart surgery.
AB  - To evaluate the effect of coronary revascularization on myocardial perfusion and
      surgical outcome regarding graft flow, we used laser Doppler flowmetry to assess
      the epicardial microcirculation in patients undergoing coronary artery bypass
      grafting (CABG) or valve replacement (VR) and electromagnetic flowmetry to
      measure graft flow in the CABG group. In the CABG group, the preoperative mean
      laser Doppler flow rate (LDF) in the epicardium of the left ventricle
      significantly increased at the end of cardiopulmonary bypass (CPB) (22 +/- 7
      arbitrary units (AU) to 60 +/- 13 AU, p < 0.001). This value further increased 10
      min after protamine infusion (66 +/- 14 AU, p < 0.01), but was significantly
      reduced 30 min later (51 +/- 14 AU, p < 0.002). Compared to the post-CPB value
      (34 +/- 10 ml/min) before protamine infusion, the mean graft flow (ml/min) to
      this area significantly increased 10 min after protamine infusion (41.3 +/- 10
      ml/min, p < 0.001) but significantly decreased 30 min later (29 +/- 9 ml/min, p <
      0.001). The preoperative mean LDF in the VR group was significantly higher than
      in the CABG group (p < 0.01). In the CABG group, there was a positive correlation
      between the LDF and graft flow at the end of CPB (r = 0.788) and 10 (r = 0.767)
      and 30 (r = 0.784) min after protamine infusion. This study shows that coronary
      bypass grafting increases the myocardial microcirculation which, together with
      graft flow, could give an early indication of the effect of surgery on myocardial
      microcirculation. Furthermore, protamine was found to be one of the factors
      contributing to graft flow reduction postoperatively and, therefore, newer
      methods of heparin reversal may be desirable.

PMID- 9160361
TI  - Cardiopulmonary bypass (CPB) for lung transplantation.
AB  - Surgeons have often been reluctant to use cardiopulmonary bypass (CPB) during
      single (SLTx) and double lung (DLTx) transplantation surgery because of the
      potential adverse sequelae of CPB including haemorrhage and activation of
      complement leading to sequestration of neutrophils and platelets in the pulmonary
      capillary bed, endothelial damage, increased capillary permeability and pulmonary
      oedema. To clarify the effect of CPB on lung transplant recipients, we reviewed
      our last four years' experience in 74 patients of whom 30 required CPB support.
      Indications for CPB were mean pulmonary artery pressure of greater than 50 mmHg,
      haemodynamic instability, hypoxia or hypercarbia. Patients undergoing SLTx were
      placed on CPB via the femoral artery and vein, while those undergoing DLTx were
      cannulated in the standard fashion using the ascending aorta and right atrium.
      All patients were administered aprotinin prior to CPB. Intraoperatively and
      postoperatively, haemorrhage was not a major problem. The 30-day mortality in the
      CPB group and the non-CPB group were 20% and 4.6%, respectively which was not
      statistically significant (p = 0.06). We conclude that CPB during lung
      transplantation is a safe, effective method to support these severely ill
      patients and should not be avoided because of concerns over adverse sequelae of
      CPB on postoperative graft function.

PMID- 9160362
TI  - Stockert roller pump generated pulsatile flow: cerebral metabolic changes in
      adult cardiopulmonary bypass.
AB  - There is evidence that during cardiopulmonary bypass (CPB), pulsatile pump flow
      improves cerebral metabolism. This was a study to explore the effect of pulsatile
      versus nonpulsatile perfusion on cerebral lactate, pyruvate, glucose and beta
      hydroxybutyrate using a Stockert roller pump. We found no significant differences
      between the arterial-venous (A-V) differences of lactate, glucose and beta
      hydroxybutyrate (p > 0.05). When the upward trend of A-V pyruvate was accounted
      for, there was again no difference (p = 0.2). Arterial lactate:pyruvate ratios
      were not significantly different between pulsatile and nonpulsatile pump flow (p
      > 0.05). Venous lactate:pyruvate ratios were significantly higher during
      pulsatile bypass, but when the downward trend was accounted for, the differences
      between pulsatile and nonpulsatile values were no longer significant (p = 0.4).
      Therefore, the metabolic changes were not significant. There was no significant
      difference in systemic vascular resistance (SVR) during pulsatile and
      nonpulsatile flow (p = 0.4). Pulsatile flow delivered by the Stockert roller pump
      appears to have no metabolic or SVR advantages in adults undergoing CPB.

PMID- 9160363
TI  - Fingertip temperature during cardiopulmonary bypass.
AB  - Temperature changes in the nasopharynx, fingertip, forearm and extracorporeal
      circuit were continuously monitored, starting 10 min before and up to 16 min into
      the rewarming period of hypothermic (32 degrees C) cardiopulmonary bypass in 14
      patients operated on for coronary artery revascularization. Arterial blood
      temperature was the first to increase after starting rewarming, followed by the
      nasopharynx and the fingertip temperatures. Fingertip temperature started to
      increase abruptly 6.2 (2.02 SD) min after rewarming started. At this point,
      nasopharyngeal temperature was 34.2 degrees C (1.42 SD) and took a further 8.3
      min to reach 37 degrees C. Assuming that increasing fingertip temperature
      indicates a central thermoregulatory response to warming, we suggest that
      nasopharyngeal temperature is a poor monitor of brain temperature. We also
      suggest that fingertip temperature may be used to monitor the point at which
      cerebral temperature reaches 'normothermia'. Further body warming, using arterial
      temperatures > or = 39 degrees C, should be avoided because of the danger of
      brain hyperthermia.

PMID- 9160364
TI  - Intermittent antegrade/selective cerebral perfusion during circulatory arrest for
      repair of the aortic arch.
AB  - If the aortic arch requires repair or replacement due to an aneurysm or
      dissection, conventional cardiopulmonary bypass (CPB) is not possible during the
      period in which the aortic arch is excluded from the circulation. This creates a
      situation in which there is no cerebral circulation. The brain needs adequate
      protection from this ischaemic insult. Hypothermic circulatory arrest (HCA),
      antegrade/selective cerebral perfusion (ASCP) and retrograde cerebral perfusion
      (RCP) are reported to exhibit their cerebral protective capabilities during
      procedures involving the aortic arch. HCA can provide adequate protection in
      procedures of short duration and avoids the complications associated with
      cerebral perfusion techniques. The main disadvantage of HCA is that the 'safe'
      duration of circulatory arrest is not clearly defined. Topical cooling of the
      head may enhance cerebral hypothermia and provide additional protection. If
      longer periods of circulatory arrest are anticipated or occur unexpectedly, we
      suggest that ASCP can offer improved cerebral protection by providing adequate
      brain perfusion and improved cerebral cooling. By using a coronary sinus
      perfusion catheter as a carotid artery cannula, it is not necessary to snare or
      clamp the carotid arteries. This technique minimizes the chance of damaging the
      carotid arteries. In this report, we describe our set-up and ASCP perfusion
      protocol for the surgical repair of an aortic arch aneurysm.

PMID- 9160365
TI  - A comparison of gaseous emboli release in five membrane oxygenators.
AB  - The purpose of this study was to compare the air handling capability of five
      currently used membrane oxygenators: the Avecor Affinity, the Bentley SpiralGold,
      the Medtronic Maxima Plus, the Sarns Turbo and the Sorin Monolyth M. A circuit
      was constructed to include a hardshell venous reservoir and roller pump. Pressure
      monitoring sites and ultrasonic microbubble detection probes were located
      proximal and distal to the oxygenator. An air injection/infusion site was
      provided proximal to the roller pump inlet. Each circuit was primed with fresh
      anticoagulated bovine blood, adjusted to a haematocrit of 25% and maintained at
      38 +/- 1 degree C. Three different bolus amounts of air (10, 20 and 40 cm3) were
      injected at three blood flow rates (3, 4.5 and 6 l/min). A 1-min infusion of air
      delivered at 1 ml/s was also administered at three blood flow rates (3, 4.5 and 6
      l/min). The hardshell reservoir was also completely emptied at each flow rate to
      simulate a massive air infusion. At any given blood flow, outlet microbubble
      counts were usually higher with greater bolus amounts of air. When indexed to the
      inlet bubble counts, the following average percent microbubbles were released
      from the outlet: Turbo 25%, Affinity 7%, Monolyth 5%, Maxima 3% and SpiralGold
      1%. With a constant air infusion of 1 ml/s, greater outlet microbubble counts
      were associated with higher blood flow rates. Again, when indexed to the inlet
      bubble counts, the following average percent microbubbles were released from the
      outlet: Turbo 44%, Affinity 25%, Maxima 19%, Monolyth 16% and SpiralGold 0%. All
      oxygenators deprimed when the hardshell reservoir was emptied and all shed
      microbubbles into the outlet blood except the SpiralGold. The results of this
      study indicate that air handling is not a simple function of blood flow pattern
      (i.e. top to bottom versus bottom to top), but also includes dynamics associated
      with oxygenator design, fibre arrangement and flow resistance.

PMID- 9160366
TI  - Coagulopathic-induced membrane dysfunction during extracorporeal membrane
      oxygenation: a case report.
AB  - This paper describes an unusual complication of membrane dysfunction during
      extracorporeal membrane oxygenation (ECMO) for treatment of neonatal respiratory
      distress. A 2.8-kg term infant presented to our facility in severe respiratory
      distress and was diagnosed with primary pulmonary hypertension. After routine
      priming of the extracorporeal circuit, the patient was placed on veno-arterial
      ECMO with 8 F arterial and 12 F venous cannulae. Transfusion criteria were
      established which included trigger values of the following: platelet count
      100,000/microliters, fibrinogen 150 mg/dl, haematocrit 40%. The ECMO course was
      uneventful until approximately the 132nd hour on support when the patient
      developed a consumptive coagulopathy, as evidenced by 55-60% reductions in both
      platelet count and fibrinogen concentrations, despite transfusion therapy. Total
      autogeneic blood product transfusion during the first 120 h of ECMO averaged 4.4
      +/- 2.2 ml/h, while the transfusion rate for the final 35 h was 7.8 +/- 3.5 ml/h.
      Coinciding with this rise in transfusion requirements was an increase in
      transmembrane pressure from 0.29 to 1.52 mmHg/ml blood flow. The patient was
      separated from ECMO after 175 h due to a continuing coagulopathy and haemothorax.
      The patient was then treated with nitric oxide therapy before succumbing on the
      twelfth postoperative day due to refractory respiratory failure. The circuit was
      dissected and significant clots found in both the venous bladder and oxygenator.
      In addition, approximately one-third of the membrane compartment had a 'fused'
      circumferential pattern of dessicated clot which interrupted blood path
      continuity. In conclusion, this report describes an unusual complication of the
      ECMO oxygenator that occurred during long-term extracorporeal life support which
      most likely resulted from a coagulopathy.

PMID- 9160367
TI  - Protein delivery from biodegradable microspheres.
AB  - The key components to the successful development of a biodegradable microsphere
      formulation for the delivery of proteins are polymer chemistry, engineering, and
      protein stability. These areas are intricately related and require a thorough
      investigation prior to embarking on the encapsulation of proteins. While each of
      these components is important for the development of a biodegradable microsphere
      formulation for protein delivery, other critical issues should also be
      considered. In particular, preclinical studies in the appropriate animal model
      are usually necessary to assess the potential feasibility of a continuous-release
      dosage form. These studies should be performed at the earliest possible stage of
      development to validate the feasibility of a controlled release formulation.
      After the utility of a controlled release formulation has been demonstrated, the
      polymer matrix should be chosen and bench-scale production of microspheres
      initiated. The only polymers presently approved for human use for controlled
      delivery are the polylactides [poly(lactic acid), poly(glycolic acid), and
      poly(lactic-coglycolic) acid]. These polymers require multiphase processes
      involving several steps to produce microspheres containing the desired protein. A
      thorough review of previous work on encapsulation with these polymers should
      provide some insight into conditions to be assessed in developing a process. Once
      a process is chosen, it must be optimized to provide the highest possible yield
      of microspheres with the desired characteristics (e.g., loading, release, size,
      etc.). Finally, the final aseptic process should be validated and methods
      generated to assess the final product. The clinical studies should then start
      upon approval of the IND application. In the future, the biotechnology industry,
      and the pharmaceutical industry in general, will be seeking new methods to
      improve the delivery of therapeutic agents such as proteins and peptides.
      Formulations like biodegradable microspheres significantly reduce health-care
      costs since fewer administrations are needed, and they provide a competitive
      advantage in markets with several competing products (e.g., LHRH agonist market).
      Further, many new indications such as neurological diseases may require a long
      term delivery system. The future success of biodegradable microsphere
      formulations will primarily depend on the commitment of the pharmaceutical and
      biotechnology industries to the development of this technology.

PMID- 9160368
TI  - Degradable controlled release systems useful for protein delivery.

PMID- 9160369
TI  - Delivery of proteins from a controlled release injectable implant.

PMID- 9160370
TI  - Protein delivery from nondegradable polymer matrices.

PMID- 9160371
TI  - Diffusion-controlled delivery of proteins from hydrogels and other hydrophilic
      systems.

PMID- 9160372
TI  - Poly(ethylene glycol)-coated nanospheres: potential carriers for intravenous drug
      administration.

PMID- 9160373
TI  - Multiple emulsions for the delivery of proteins.
AB  - Multiple emulsions are unique in that a true liquid phase is maintained separate
      from an external aqueous phase. This may be especially important for bioactive
      molecules that cannot be appropriately stabilized in the solid state. In
      addition, the separation of aqueous phases enables highly specialized
      environments, conducive to protein activity, to be prepared. The physical
      instability of conventional systems remains a major factor limiting their wider
      application. Attempts to improve the physical stability of the aqueous
      dispersions through interfacial complexation and the use of micro-emulsions are
      improving the short-term stability. As an alternative approach, solid-state
      emulsions attempt to store the multiple emulsion as a solid. Although solid-state
      emulsions appear to have the potential to be useful protein delivery systems, a
      substantial experimental data base has yet to be generated.

PMID- 9160374
TI  - Transdermal peptide delivery using electroporation.

PMID- 9160375
TI  - Protein delivery with infusion pumps.
AB  - When a therapeutic effect is optimized by precise control of specific temporal
      patterns of plasma levels, infusion offers distinct advantages over oral
      administration, bolus injection, or depot delivery of polypeptides. The
      limitations of oral delivery are well known, and although research is under way
      into development of carrier systems that prevent degradation of labile agents, it
      is unlikely that the variances in absorption will meet the need for precise
      control. Depot delivery from subcutaneous or intramuscular implants presents a
      difficult situation when local tissue reactions to the agent sometimes occur.
      Removal of a depot system in the event of adverse reactions presents additional
      difficulties. Bolus injections are unable to sustain constant plasma levels
      unless the drug half-life is long or the injections are frequently administered.
      Insulin injections, for example, would be required every 30-60 minutes to
      approximate the plasma levels provided by a continuous infusion; such frequent
      injections would not be practical on a 24-hour basis. For the developer of new
      polypeptides, parenteral administration offers the most direct route to the
      marketplace. The step from periodic injections to tightly controlled infusion is
      a logical progression as compared with modification of the molecules or vehicles
      to obtain equivalent profiles. In Table II several different types of devices
      that can be used for infusion of proteins are compared. Microelectronics have
      played a major role in the miniaturization of infusion devices and undoubtedly
      will continue to do so. Micromachining, a spin-off technology of integrated
      circuit manufacture, will also find application in small infusion devices. In the
      future, we will have cost-effective disposable devices (Saaman et al., 1994)
      built on this technology that are programmable and thus can be adapted to meet
      each individual therapeutic need (Horres, 1994). We can also expect to see more
      closed-loop drug delivery systems where biosensors and infusion devices are
      combined to optimize a particular therapy. Recent positive results obtained in
      diabetics by a decade on tight glucose control may forecast a resurgence of
      popularity of insulin pumps. At the other end of the spectrum, low-cost, small,
      and simple-to-use osmotically powered systems are close to being marketed; these
      systems will make infusion almost as convenient as transdermal patches. We will
      also see major advances in how drugs and devices are interfaced. Prefilled and
      ready-to-use drug cartridges have proven to be efficient in surgical and
      emergency medicine and can greatly improve most infusion applications. It is
      anticipated that coded, prefilled cartridges or pouches will be automatically,
      recognized by preprogrammed pumps to reduce operator labor and entry error.

PMID- 9160376
TI  - Oral delivery of microencapsulated proteins.

PMID- 9160377
TI  - Controlled delivery of somatotropins.

PMID- 9160378
TI  - Insulin iontophoresis.

PMID- 9160379
TI  - Insulin formulation and delivery.

PMID- 9160380
TI  - Results of 12 years' combined maternal serum alpha-fetoprotein screening and
      ultrasound fetal monitoring for prenatal detection of fetal malformations in
      Havana City, Cuba.
AB  - Progressively since 1982 and as part of a nationwide programme for the diagnosis
      and prevention of genetic diseases, maternal serum alpha-fetoprotein (MS-AFP)
      screening and ultrasound fetal monitoring has been implemented in all pregnant
      women in Cuba. In Havana City, 328,983 pregnant women underwent MS-AFP screening
      between 15 and 19 weeks of gestational age. With a cut-off level of > or = 2
      multiples of the normal median (MOM), 1767 amniocenteses were carried out to
      determine the levels of amniotic fluid AFP and 685 malformed fetuses were
      diagnosed. By ultrasound fetal monitoring, an additional 686 malformed fetuses
      were detected. As a result of the programme, the birth prevalence of neural tube
      defects has fallen by 90 per cent.

PMID- 9160381
TI  - The association of early-onset fetal growth restriction, elevated maternal serum
      alpha-fetoprotein, and the development of severe pre-eclampsia.
AB  - From Antenatal Diagnostic Center referrals over 22 months, consultations for
      early-onset fetal growth restriction versus skeletal dysplasia were
      retrospectively identified. Those with elevated maternal serum alpha-fetoprotein
      (MSAFP) levels are the focus of this report. All had an early ultrasound
      confirming menstrual dates and subsequent sonography at < 28 weeks with at least
      two fetal biometric measures delayed by > or = 2 standard deviations from mean
      values. Of the five patients identified, the mean gestational age at the time of
      diagnosis of fetal growth restriction was 23.3 +/- 2.9 weeks. All had normal
      karyotypes and normal amniotic fluid AFP. None of the patients had evidence of
      hypertension or pre-eclampsia at diagnosis of fetal growth restriction. All five
      gravidas subsequently developed severe pre-eclampsia from 5.5 to 12.5 weeks after
      documentation of fetal growth delay. Three developed HELLP syndrome. Pregnancies
      were continued a mean duration of 10-2 weeks, with all five delivering at preterm
      gestations (mean = 33.5 +/- 1.7 weeks) for maternal indications of severe pre
      eclampsia. Unexplained early-onset fetal growth restriction in conjunction with
      unexplained elevations of MSAFP together consistently heralded the subsequent
      development of severe pre-eclampsia.

PMID- 9160383
TI  - Umbilical Doppler velocimetry in fetuses with trisomy 18 at 10-18 weeks'
      gestation.
AB  - The aim of our study was to obtain measurements of the umbilical artery
      pulsatility index (PI) in pregnancies before invasive procedures for prenatal
      diagnosis, in order to investigate its potential prognostic value in predicting
      trisomy 18. We performed a prospective study including 1785 consecutive women
      from 10 to 18 weeks with singleton pregnancies undergoing chorionic villus
      sampling (n = 559) or genetic amniocentesis (n = 1226) in our unit. Doppler
      measurements were performed transvaginally (tenth to 13th week of gestation) or
      transabdominally (14th to 18th week of gestation) immediately before the invasive
      procedure. In 7 out of 10 fetuses subsequently diagnosed as trisomy 18, the PI
      was above the 95th centile, providing a detection rate of 70 per cent, a
      specificity of 95.1 per cent, a positive predictive value of 7.7 per cent, and a
      negative predictive value of 99.8 per cent. When the 90th percentile was assayed
      as a cut-off, the efficacy of PI as a marker of trisomy 18 yielded a sensitivity
      of 90 per cent and a specificity of 90.4 per cent, with a positive predictive
      value of 5.2 per cent and a negative predictive value of 99.9 per cent. We
      suggest that although the use of a single PI measurement for screening purposes
      needs to be confirmed by further investigation, trisomy 18 fetuses show an
      abnormal increase in umbilical PI in the first half of pregnancy, and its
      relation to the early onset of fetal growth retardation needs to be further
      explored.

PMID- 9160382
TI  - A prospective comparative study on transabdominal chorionic villus sampling and
      amniocentesis performed at 10-13 week's gestation.
AB  - Women with single, viable pregnancies at 10 + 5 to 13 + 6 weeks, gestation who
      requested fetal karyotyping for maternal age, parental anxiety, or a previous
      history of chromosomal aberration were offered participation in this study. With
      a transabdominal ultrasound-guided technique, early amniocentesis (EA) was
      performed on 147 women and chorionic villus sampling (CVS) on 174. Spontaneous
      fetal loss occurred in 6.8 per cent in the EA group and 1.7 per cent in the CVS
      group. This difference was significant with a confidence interval (CI) of 0.6-9.6
      per cent. There was also a significant difference in the need for repeat testing
      between the groups. In the EA group a repeat test was required in 19.0 per cent
      due to culture and sample failures, while 5.2 per cent of the women in the CVS
      group needed repeat testing because of ambiguous results. This prospective study
      comparing EA and CVS shows that the risk of fetal loss is higher and repeat
      testing is needed more after EA.

PMID- 9160384
TI  - Sonographic assessment of the fetal palpebral fissure slant--an additional tool
      in the prenatal diagnosis of syndromes.
AB  - Several syndromes and aneuploidies are associated with ocular abnormalities
      including up- and down-slanting palpebral fissures. We describes a technique for
      the sonographic assessment of the fetal palpebral fissure slant which was used in
      70 normal pregnancies from 14 to 36 weeks of gestation. In a frontal view of the
      fetal face, the inferior angle between the palpebral fissure and the midline of
      the skull was determined. The median angle was 89 degrees, with a range from 87
      degrees to 90 degrees. In selected cases, sonographic assessment of the fetal
      palpebral fissure slant may be a helpful additional tool in the prenatal
      diagnosis of syndromes, as demonstrated in a fetus with Seckel syndrome
      associated with downslanting palpebral fissures and in a fetus with Down's
      syndrome associated with upslanting palpebral fissures.

PMID- 9160385
TI  - Early ultrasound prediction of pregnancies affected by homozygous alpha
      thalassaemia-1.
AB  - Homozygous alpha-thalassaemia-1 is conventionally diagnosed by invasive testing
      on all at-risk pregnancies. We evaluated the diagnostic efficacy of non-invasive
      abdominal ultrasonographic cardiothoracic ratio measurement in 62 pregnancies at
      13-14 weeks and 75 pregnancies at 17-18 weeks. This performed better than
      placental thickness measurement. Using a cardiothoracic ratio cut-off level of >
      or = 0.5, 75 per cent of affected pregnancies were detected at 13-14 weeks and
      all cases were detected at 17-18 weeks. False-positive rates were 7 and 8 per
      cent, respectively. There was no false-positive diagnosis if the cardiothoracic
      ratio was > or = 0.53. With this approach, invasive procedures can be selectively
      performed and fewer pregnancies will be lost unnecessarily. The reduction in
      medical expenses is likely to be substantial.

PMID- 9160386
TI  - Prenatal detection of chromosome aneuploidies by fluorescence in situ
      hybridization: experience with 2000 uncultured amniotic fluid samples in a
      prospective preclinical trial.
AB  - Successful rapid prenatal detection of selected numerical chromosome
      abnormalities by using fluorescence in situ hybridization (FISH) on uncultured
      amniotic fluid samples has been described by Klinger et al. (1992) and Ward et
      al. (1993, 1997). Using essentially the same FISH protocol and identical probes
      specific for chromosomes 21, 18, 13, X, and Y, we prospectively compared the
      results of FISH and conventional cytogenetics on 2000 amniotic fluid cell
      samples. The 1-day FISH assay yielded discrete differences in the signal profiles
      between cytogenetically disomic, i.e., normal, and trisomic samples. Due to
      intermittent absent Y-signals, the assay differentiated less well between samples
      with cytogenetically normal and abnormal sex chromosome complements. The assay
      efficiency, and thus the clinical utility, was affected by (1) unsuccessful
      hybridizations (7 per cent of all hybridizations), (2) hybridizations with less
      than 50 scorable nuclei (19 per cent of all hybridizations), and (3) visibly
      contaminated samples with possible maternal cell contamination (14 per cent of
      all samples). As a result, we were not able to reproduce the results of Klinger
      et al. (1992) and Ward et al. (1993, 1997).

PMID- 9160387
TI  - Mutation-based prenatal diagnosis of Herlitz junctional epidermolysis bullosa.
AB  - Epidermolysis bullosa (EB) is a group of heritable diseases which manifest with
      blistering and erosions of the skin and mucous membranes. Due of life-threatening
      complications and significant long-term morbidity associated with the severe,
      neonatal lethal (Herlitz) form of junctional EB (H-JEB), there has been a demand
      for prenatal diagnosis from families at risk for recurrence. Previously, the only
      reliable method of prenatal diagnosis of EB was a fetal skin biopsy performed at
      16-20 weeks' gestation and analysed by electron microscopy. Recently, the genes
      LAMA3, LAMB3, and LAMC2, encoding the polypeptide subunits of laminin 5, an
      anchoring filament protein, have been shown to contain mutations in H-JEB. In
      this study, direct detection of pathogenetic mutations in the laminin 5 genes was
      used to perform polymerase chain reaction (PCR)-based prenatal testing. DNA was
      obtained by chorionic villus sampling (CVS) at 10-15 weeks or amniocentesis at 12
      19 weeks' gestation in 15 families at risk for recurrence of JEB. In 13 cases,
      the fetus was predicted to be either genetically normal or a clinically
      unaffected carrier of a mutation in one allele. These predictions have been
      validated in all cases by the birth of a healthy child. In two cases, an affected
      fetus was predicted, and the diagnosis was confirmed by subsequent fetal skin
      biopsy. These results demonstrate that DNA-based prenatal testing offers an
      early, expedient, and accurate method of prenatal diagnosis or an exclusion of
      Herlitz JEB.

PMID- 9160388
TI  - First-trimester diagnosis of Smith-Lemli-Opitz syndrome.
AB  - We report here the prenatal diagnosis of Smith-Lemli-Opitz (SLO) syndrome in the
      first trimester by direct measurement of 7-dehydrocholesterol (7-DHC) in a
      chorionic villus (CV) biopsy. The proband was diagnosed clinically at birth and
      the diagnosis was confirmed biochemically by demonstrating elevated 7-DHC in
      plasma. The family pursued prenatal diagnosis in their fourth, fifth, and sixth
      pregnancies. The fourth pregnancy spontaneously miscarried at 9 weeks' gestation.
      Analysis in both direct and cultured curetting tissue (identified as similar to
      CV tissue) showed an abnormal tissue neutral sterol pattern with an elevated 7
      DHC concentration. The fifth pregnancy also miscarried spontaneously at 9 weeks
      but no tissue of unequivocal fetal origin could be identified to allow
      biochemical investigation. In the sixth pregnancy, ultrasound examination at the
      time of CV sampling showed a thickened nuchal fold. Direct analysis of the CV
      sample revealed elevated levels of 7-DHC consistent with the diagnosis of SLO.
      The pregnancy was terminated and both fetal tissue and cultured fetal cells
      showed marked increases in 7-DHC, confirming the prenatal diagnosis.

PMID- 9160389
TI  - 47,XXY (Klinefelter syndrome) and 47,XYY: estimated rates of and indication for
      postnatal diagnosis with implications for prenatal counselling.
AB  - Cytogenetic surveys of neonates have found that approximately one boy in 500 is
      born with an extra sex chromosome. Some of these boys are now being diagnosed
      when prenatal karyotyping is done for the detection of Down syndrome and other
      major aneuploidies. This study estimates what proportion of those not detected
      prenatally will be diagnosed postnatally and what the indications for karyotyping
      are likely to be. We ascertained all 47,XXY and 47,XYY males detected prenatally
      and postnatally (during the 4 years 1990-1993) in the three cytogenetic
      laboratories in the North Thames (West) region. The age at diagnosis and
      indication for karyotyping were noted for cases diagnosed postnatally. Less than
      10 per cent of the estimated number of affected fetuses were detected prenatally.
      This study suggests that most males born with these chromosome patterns will go
      through life without being karyotyped, that the commonest indication for a 47,XYY
      male to be karyotyped will be developmental delay and/or behaviour problems, and
      that the commonest indication for a Klinefelter male to be karyotyped will be
      hypogonadism and/or infertility. It would appear that most undiagnosed 47,XXY and
      47,XYY males do not look or behave in a manner which prompts testing for a
      chromosome abnormality.

PMID- 9160390
TI  - Prenatal diagnosis of a half-cryptic translocation using chromosome
      microdissection.
AB  - This report describes a case of a paternal balanced, but apparently non
      reciprocal, insertion of chromosome 15 material into the short arm of chromosome
      17 with difficulties in distinguishing between the normal and the deleted
      chromosome 15 in prenatal karyotype analysis. Microdissection and degenerate
      oligonucleotide-primed polymerase chain reaction (DOP-PCR) of the paternal 17p+
      chromosome was performed to generate a painting probe specific for the small
      region inserted from chromosome 15 into chromosome 17. Fluorescence in situ
      hybridization (FISH) of this probe simultaneously with a differentially labelled
      15q microdissection probe enabled the identification of a balanced karyotype in
      the fetus. In this case, microdissection combined with FISH was the only method
      for obtaining a reliable result within the short time available for prenatal
      diagnosis. In addition, it was possible to identify with certainty the originally
      suspected reciprocal translocation as an insertion of the region 15q22.3-->q23 or
      24 into the sub-telomeric region of 17p [ins(17;15)(p13;q22.3q23 or 24)]. Thus,
      the chromosomal defect of two family members with a partial trisomy of chromosome
      15 having severe mental retardation and dysmorphic features was identified
      precisely.

PMID- 9160391
TI  - Misinterpretation of trisomy 18 as a pseudomosaicism at third-trimester
      amniocentesis of a child with a mosaic 46,XY/47,XY, +3/48,XXY, +18 karyotype.
AB  - False-negative trisomy 18 has been reported after chorionic villus sampling, but
      not after amniocentesis. We describe a double aneuploidy in cultured amniocytes
      that was initially misinterpreted as a pseudomosaicism. A patient was referred at
      31 weeks of gestation because of fetal anomalies at ultrasound examination.
      Karyotyping of amniocytes showed a 47,XY, +3 karyotype in 61 clones and a 48,XXY,
      +18 karyotype in one clone. The latter was interpreted as a pseudomosaicism, the
      more since a second amniocentesis revealed only cells with a 47,XY, +3 karyotype.
      At 36 weeks gestational age, a boy was born with congenital anomalies suggestive
      of trisomy 18. A blood culture showed a 48,XXY, +18 karyotype, while in
      fibroblasts a 47,XY, + 3/48,XXY, +18 mosaicism was found. Umbilical cord and
      bladder epithelial tissue also revealed normal 46,XY cells, besides the aneuploid
      cells. Therefore, the child proper had a 46,XY/47,XY, +3/48,XXY, +18 mosaicism
      with the clinical symptoms of trisomy 18. To the best of our knowledge, this is
      the first report of a false-negative result of trisomy 18 together with three sex
      chromosomes after amniocentesis.

PMID- 9160392
TI  - Prenatal diagnosis of the 22q11 deletion syndrome.
AB  - A 27 weeks gestation fetus, evaluated because of polyhydramnios, was found by
      echocardiography to have an interrupted aortic arch type B. Because of the known
      association between this malformation and DiGeorge syndrome, an amniocentesis was
      performed. Fluorescence in situ hybridization revealed a 22q11 deletion. This is,
      to our knowledge, the first report of prenatal detection of a fetus with 22q11
      deletion in the absence of a family history.

PMID- 9160393
TI  - Prenatal diagnosis of cephalothoracopagus janiceps monosymmetros.
AB  - We report a case of cephalothoracopagus janiceps monosymmetros that was diagnosed
      prenatally by ultrasound at 23 weeks' gestation. Obstetric ultrasound
      demonstrated conjoined female twins with a single fused cranial vault irregular
      in contour, duplicated cerebra, one face, two eyeballs, a fused thorax, two
      hearts, two thoracic spines, eight limbs, and polyhydramnios. The pregnancy was
      terminated and all the features described prenatally were observed at necropsy.
      The asymmetrical fused faces consisted of a ventral humanoid face with
      micrognathia, microphthalmia, low-set ears, a normal nose, and an opposite
      reduced face with partial facial features of a central narrowed fissure and
      paired synotic ears. The conjoined twins had fused umbilical cords, omphalocoele,
      and a single oesophagus, stomach, and duodenum, but duplicated pancreases,
      spleens, and central nervous, cardiopulmonary, hepatic, and genito-urinary
      systems. The common gastrointestinal tract bifurcated at the level of the
      jejunum. Our case documents a very uncommon variety of asymmetrical
      cephalothoracopagus janiceps with duplicated central nervous systems.

PMID- 9160394
TI  - Prenatal diagnosis of triploidy using fetal cells in the maternal circulation.

PMID- 9160395
TI  - Current awareness in prenatal diagnosis.

PMID- 9160396
TI  - Effect of prenatal T4 treatment in neonatal morbidity: preliminary findings.
AB  - We report our experience with the use of intra-amniotic thyroxine to accelerate
      fetal maturation in preterm delivered infants. One hundred and fourteen infants
      who had received 500 micrograms of thyroxine weekly prenatally until an L/S ratio
      greater or equal to 2.0 was achieved, were compared to 113 premature infants who
      had not been given thyroxine or steroids prenatally. After stratification by
      weight, the relative incidence of respiratory distress syndrome (RDS), patent
      ductus arteriosus (PDA), necrotizing enterocolitis (NEC) and intraventricular
      hemorrhage (IVH) were compared. A decrease in the incidence of RDS was observed
      in the infants with birth weight between 1000 and 1500 g who had received more
      than one dose of intra-amniotic thyroxine. No difference in the incidence of RDS
      was observed in infants with birth weight of less than 1000 g or over 1500 g. One
      dose of thyroxine had no effect in decreasing the incidence of RDS, PDA, NEC, and
      IVH in any of the groups. We conclude intra-amniotic thyroxine seems to decreases
      the incidence of RDS in very low birth weight infants.

PMID- 9160397
TI  - Survival and quality of life in HIV-positive patients treated with a
      polyantigenic immunomodulator.
AB  - A polyantigenic immunomodulator (PAI), previously known as polyantigenic vaccine,
      which consists of a mixture of antigens of inactivated bacteria with antigens of
      influenza virus in a peanut-oil-arlacel-A-aluminium monoesterate emulsion,
      increased tumor resistance and induced tumor regression in tumor bearing mice.
      This report presents clinical and laboratory data that demonstrate the effect of
      PAI in long term prolongation of disease free state in HIV positive patients. A
      total of 40 patients, 35 males and 5 females, with a mean age of 41.1 +/- 10.5
      years, ranging from 28 to 68 years, HIV positive by (ELISA and Western Blot),
      with no restriction on the CD4 + T lymphocytes counts, were included in this open
      study. The PAI regimen was one subcutaneous injection per week for patients with
      < 400 CD4 + lymphocytes and one monthly injection for patients with CD4 + count >
      400. All patients were monitored at different intervals for lymphocyte counts,
      clinical condition and treatment toxicity. After a follow up of eight years 81%
      of the patients were alive and 47% were free of disease. In patients without
      AIDS, the weight was 153.9 +/- 28 pounds pre-PAI and 164.6 +/- 27 (P = 1.2 x 10(
      4); the CD4 + lymphocyte count was 795 +/- 421 pre-PAI and 585 +/- 279 post PAI
      (P = 0.08). In patients alive with AIDS, the weight was 159.5 +/- 32 pre-PAI and
      163.9 +/- 32 pounds post-PAI (P = 0.8); the CD4 + lymphocyte counts was 491 +/-
      255 pre-PAI and 298 +/- 142 post-PAI (P = 0.08); and five AIDS-related infections
      occurred in five patients. In patients who died the weight was 157.7 +/- 23 pre
      and 146.8 +/- 30 post (P = 0.10); and the CD4 count was 340.7 +/- 149 pre and
      103.4 +/- 88 post (P = 0.0057). All died with infection. No toxicity with the use
      of PAI was reported. PAI improves disease free survival and quality of life in
      HIV + patients.

PMID- 9160398
TI  - An update on the discovery, pathophysiological actions, clinical manifestations
      and possible physiology of parathyroid related peptide.
AB  - PTHrP has had an unidentified role in medicine since 1930, when Albright
      described a patient with renal cortical cell carcinoma with hypercalcemia. Since
      then hypercalcemia has been recognized as the most common paraneoplastic
      syndrome. At that time the concept of "ectopic PTH syndrome" was introduced, and
      remained in literature until the true etiology was finally described. In the
      early 1970's Roof and Benson presented evidence that PTH in humoral hypercalcemia
      differed from "authentic" PTH. This marked the starting point for researchers to
      try identifying the molecule that mimicked PTH action and structure. This
      molecule, named parathyroid-related peptide, has been associated to hypercalcemia
      seen with solid tumors, such as squamous cell carcinoma of the lung and renal
      cortical cell carcinoma. PTHrP has been demonstrated to have similar actions to
      PTH but to differ in decreasing osteoblastic activity while increasing
      osteoclastic activity. The more fascinating finding was the presence of the PTHrP
      genes throughout the body, mostly the lactating breast as well as the heart,
      lungs and skin among others. Despite its identification, finding its
      physiological roles on normal tissue still remains to be clarified.

PMID- 9160399
TI  - A cellular approach to the study of complex natural behavior patterns in the
      ragged sea hare (Bursatella leachii), a marine invertebrate indigenous to Puerto
      Rico.
AB  - The ragged sea hare (Bursatella leachii), an aplysiid mollusc indigenous to the
      tropical waters of Puerto Rico, possesses numerous properties that make it
      suitable for a neuroethological approach to the study of complex behavior
      patterns. Field studies spanning three years have established a location and
      season of Bursatella availability on the north coast of the island. In the
      natural habitat, the Bursatella exhibit a daily rhythm of behavior patterns in
      which feeding-related activities predominate during the day and reproductive
      behaviors predominate at night. Some aspects of this natural pattern persist in
      animals held in the laboratory. The Bursatella nervous system contains large
      neurons, some of which appear to be homologous to cells that have been
      characterized extensively in related species. Following isolation of the nervous
      system, neural centers associated with feeding movements and locomotion retain
      extraordinarily robust rhythm generating capabilities. It is proposed that this
      species offers unique opportunities for deriving general principles governing the
      regulation and integration of central pattern generator circuits underlying
      complex natural behavior patterns.

PMID- 9160400
TI  - Puerto Rican youth in drug treatment facilities: who volunteers for HIV testing?
AB  - This paper examines the characteristics of youngsters in drug treatment who
      volunteer for AIDS testing in comparison to those who do not. HIV Antibodies
      testing was offered on a voluntary basis to a sample of 250 Puerto Rican
      youngsters enrolled in three ambulatory drug treatment centers in 1991. Sixty-six
      percent of the youngsters agreed to take the test. Male adolescents who
      volunteered reported fewer years of education and were more likely to have
      dropped-out of school. Consistent with research findings among adults, those
      adolescents at greater risk of HIV infection as measured by drug use and sexual
      behaviors were more likely to volunteer for on-site testing for HIV infection.
      Higher rates of alcohol use and marijuana use differentiated volunteers from
      those who did not. Among the sexual behaviors investigated, number of partners,
      engaging in less risk reduction practices, having a sexual partner who had used
      illicit drugs and using condoms to avoid STD's were found to be significantly
      higher in volunteers.

PMID- 9160401
TI  - Carbamazepine-induced sinus node dysfunction.
AB  - Carbamazepine, a drug used for the treatment of epilepsy and neuralgias, may
      exert hazardous effects on the cardiac conduction system. We report such a case
      of symptomatic brady-arrhythmia occurring in a 43-years-old male while on therapy
      with carbamazepine. Additionally, a literature review is made of previous cases
      of carbamazepine-induced sinus mode, AV node and His-Purkinje conduction
      disturbances.

PMID- 9160402
TI  - Role of allied health professionals in policy making and legislative actions.

PMID- 9160403
TI  - Multi-competencies: a challenge for the allied health professions.
AB  - The 21st century brings new challenges to academic medical centers and
      universities who are responsible to prepare health professionals. These academics
      medical centers and universities need to respond more effectively to the demands
      of the health market place. The Health Care reform has brought about many changes
      within the health care field. Perhaps none of these changes is more dramatic than
      the impact on the allied health professional. No longer can this professional
      rely on "skills of old" to compete in today's market place. One of the most
      important strategy will be the transformation of the specialized allied health
      professional to a multi-skilled, multi-layered generalized health care provider.
      Advance practice nurses and paramedics will take over some of physicians' duties
      such as diagnose and prescription of medications and treatment to the patients.
      For individuals to move vertically to positions and to be marketable in health
      care settings, they need to increased their personal and technical skills, and
      health care knowledge. In order to survive, the health care professional will
      need to gain increased competencies and skills in several areas rather than
      obtain proficiency in one specific area.

PMID- 9160404
TI  - Technology: the road to improved health care.

PMID- 9160405
TI  - Past, present and future of allied health professions in Florida.

PMID- 9160406
TI  - Mucolytic and mucokinetic therapy.

PMID- 9160407
TI  - Pulmonary protective and vasodilator effects of a standardized Panax ginseng
      preparation following artificial gastric digestion.
AB  - We have previously demonstrated that purified ginsenosides produce pulmonary
      vasodilation and prevent effects of free radical injury on the lung. We examined
      the effect of artificially digested standardized ginseng preparation G115 in
      perfused rabbit lungs. G115 was incubated in artificial gastric juice (0.03 M
      NaCl + 0.08 M HCl) 37 degrees C for 1 h, and artificial intestinal juice (0.05 M
      KH2PO4 + 0.02 M NaOH) 37 degrees C for 5 h, neutralized with NaOH and
      lyophilized. Pulmonary vasoconstriction was induced with U46619, and cumulative
      additions of G115 in undigested, gastric digested and gastric and intestinal
      digested forms were made to the perfusate. In separate experiments, oxygen free
      radical injury by electrolysis was produced in the presence of G115 in the
      perfusate and ACh-induced vasodilation assessed before and after injury.
      Undigested, gastric digested and combined gastric and intestinal digested G115
      significantly dilated lungs (44%, undigested; 26%, gastric digested; 45%, gastric
      and intestinal digested). In addition, both undigested (-27 +/- 5% vs. -24 +/-
      5%) as well as gastric and intestinal digested G115 (-23 +/- 3% vs. -16 +/- 2%)
      preserved ACh-induced vasodilation following injury. Artificially digested G115
      is a pulmonary vasodilator which protects against free radical injury, suggesting
      that oral G115 has the same effects.

PMID- 9160409
TI  - Attenuation of airway hyperresponsiveness during acute viral infection using the
      21-aminosteroid U-83836E in rats.
AB  - Respiratory viral infections have been associated with exacerbations of asthma in
      humans, and are known to produce airway obstruction and hyperresponsiveness in
      rats. Virus-induced airway dysfunction may result in part from inflammatory cells
      and their products, and agents that target these mechanisms might therefore
      attenuate viral airway injury. The 21-aminosteroid class of drugs has been
      reported to attenuate tissue injury in a variety of models, and we hypothesized
      that U-83836E, an orally-active aminosteroid, would prevent the development of
      airway dysfunction during acute viral illness. Adult rats were inoculated with
      either parainfluenza type 1 (Sendai) virus or sterile vehicle, treated with
      either U-83836E 20 mg/kg or water by oral gavage twice daily, and studied on
      postinoculation day 5, 6 or 7. Anesthetized, paralysed, mechanically ventilated
      rats were placed in a body plethysmograph for measurements of airway obstruction
      (resistance, dynamic compliance, eucapneic PaO2), and responsiveness to i.v.
      methacholine; lungs were lavaged to obtain inflammatory cells. The water-treated
      virus group was significantly different from the non-infected controls for all
      variables. Virus-induced hyperresponsiveness was attenuated (P = 0.027) by
      aminosteroid treatment, although airway obstruction and inflammation were not
      improved by the treatment. We conclude that 21-aminosteroids may protect airways
      from virus-induced hyperresponsiveness.

PMID- 9160408
TI  - The role of cyclooxygenase and 5-lipoxygenase metabolites in potentiated
      endothelin-1-evoked contractions in bovine bronchi.
AB  - We have previously shown that angiotensin II (AII) potentiates responses evoked
      by endothelin-1 (Et-1). In the present study, the additional ability of hypoxia
      or phorbol 12, 13-dibutyrate (PDBu) to evoke hyperreactivity was examined. In
      addition, the role of cyclooxygenase and 5-lipoxygenase metabolites of
      arachidonic acid in the potentiation evoked by AII, hypoxia or PDBu was studied,
      using indomethacin and nordihydroguaiaretic acid (NDGA). The involvement of
      protein kinase C in the enhanced response was examined using staurosporine.
      Contractions were measured isometrically from rings of bovine bronchi.
      Contractions evoked by Et-1 alone were unaltered by indomethacin (10(-6)M), NDGA
      (10(-5)M) or staurosporine (3 x 10(-8)M). AII (3 x 10(-7)M), hypoxia (4% O2) or
      PDBu (10(-8)M) each significantly potentiated the contractions evoked by Et-1.
      Indomethacin (10(-6)M) virtually abolished the effect of AII, hypoxia or PDBu.
      NDGA (10(-5)M) reversed the potentiating effect of both AII and hypoxia and
      partially reversed PDBu-evoked enhancement of Et-1-mediated responses.
      Staurosporine (3 x 10(-8)M) abolished the ability of AII or PDBu, but not
      hypoxia, to enhance Et-1-mediated contractions. In conclusion, AII, hypoxia and
      PDBu evoke hyperresponsiveness which is mediated by prostanoids and/or
      leukotrienes, the precise nature of which remains to be elucidated. Differences
      in the ability of staurosporine to reverse AII- and hypoxia-induced
      hyperreactivity suggests, however, that these conditions may generate different
      eicosanoids.

PMID- 9160410
TI  - The effect of bacterial toxins on levels of intracellular adenosine nucleotides
      and human ciliary beat frequency.
AB  - Toxins that slow ciliary beat are virulence determinants of bacteria that infect
      or invade ciliated epithelial surfaces. We have previously shown that the effect
      of the Pseudomonas aeruginosa toxin pyocyanin on ciliary beat is associated with
      a fall in intracellular cAMP and ATP. We have now investigated whether reduction
      in intracellular adenosine nucleotides might be a common mechanism of action of
      other bacterial toxins which slow ciliary beat. Two other P. aeruginosa toxins, 1
      hydroxyphenazine (1-HP) and rhamnolipid, and two Haemophilus influenzae fractions
      produced by gel filtration of broth cultures were tested. The effect on human
      nasal epithelium ciliary beat frequency (CBF), and intracellular cAMP and ATP
      were measured, and the effect of two pharmacological agents, dibutyryl cAMP and
      salmeterol, on these changes was assessed. 1-HP, rhamnolipid and the two H.
      influenzae fractions slowed CBF before there was significant release of lactate
      dehydrogenase from the cells. The toxins also caused a fall in intracellular cAMP
      and ATP. Dibutyryl cAMP and salmeterol at the concentrations used do not increase
      baseline CBF, but diminished the fall in CBF and intracellular adenosine
      nucleotides. The cAMP and ATP levels in these studies were combined with those
      previously obtained with pyocyanin. there was a good correlation between cAMP and
      ATP levels and CBF. Bacterial toxins which slow CBF may act by causing a fall in
      intracellular adenosine nucleotides, and agents which stimulate cAMP may prevent
      toxin-induced slowing of ciliary beat.

PMID- 9160411
TI  - Effect of leukotriene D4 on ciliary activity in human, guinea-pig and rat
      respiratory mucosa.
AB  - Leukotriene D4 (LTD4) is a potent bronchoconstrictor and inflammatory mediator in
      asthma. Data concerning the effects of LTD4 on ciliary function in the
      respiratory tract are sparse and contradictory. The purpose of the present study
      was to clarify the effects of LTD4 on mucociliary activity using the tracheal
      mucosa of two laboratory animal species, guinea-pig and rat, as well as human
      nasal mucosa. The ciliary beat frequency (CBF) was measured photoelectrically and
      determined by Fast Fourier Transform computer analysis. Additionally the
      structure of ciliated epithelia of guinea-pig trachea after LTD4-immersion was
      investigated using a scanning electron microscope (SEM). In all tissues, LTD4
      increased CBF showing a bell-shaped dose-response curve. The maximum effect was
      75 +/- 30% in guinea-pig at 10(-9) mol/l, 119 +/- 49% in rat at 10(-7) mol/l, and
      86 +/- 28% at 10(-6) mol/l in human tissue. In guinea-pig tracheal mucosa, there
      was an indication of an increase in the amount of mucus and disorientation of
      cilia were seen by SEM after immersion in LTD4. These findings suggest that LTD4
      stimulates ciliary activity, but impairs the orientation of cilia.

PMID- 9160412
TI  - Intramural elastase injection increases responsiveness of isolated bronchial
      segments.
AB  - In cartilaginous bronchi, the smooth muscle is attached to the adventitial
      cartilage by a fibro-elastic matrix. In pigs, this matrix is stretched during
      muscle contraction so the inner airway wall reversibly uncouples from the outer
      wall. We hypothesized that inflammatory cell derived proteases may degrade this
      fibro-elastic matrix, increasing airway responsiveness. Airway responsiveness was
      determined from the sensitivity of perfused 2.0-3.5 mm id porcine bronchial
      segments to acetylcholine (ACh 10(-6)-10(-2)M) and from airway lumen narrowing
      imaged directly using a fibre-optic endoscope and video camera. Elastase (3
      microliters, 1% solution) injected between the cartilage and the smooth muscle
      doubled sensitivity to ACh (P < 0.001) in perfused segments. Maximal airway
      narrowing to 10(-2) ACh was also increased from 54% to 60% (P < 0.05). Smooth
      muscle contraction, recorded isometrically, was not increased by elastase. We
      conclude that proteases may increase airway wall uncoupling in vitro, possibly by
      reducing the wall load, and thereby increasing responsiveness.

PMID- 9160413
TI  - Speeds of action of single doses of formoterol and salbutamol compared with
      placebo in reversing methacholine-induced bronchoconstriction.
AB  - We compared the speeds of action of two doses of the long acting beta-agonist
      formoterol (12 micrograms and 24 micrograms) with those of salbutamol (400
      micrograms) and placebo using a double-blind, randomized, cross-over study design
      in 16 asthmatic subjects. A methacholine test was used on four separate study
      days to produce a standardized degree of bronchoconstriction (a decrement in FEV1
      > or = 20%) and one of the study medications as dry powder was administered
      immediately afterwards via an Aerolizer inhaler device. The speeds of recovery
      were estimated from measurements of FEV1 over the following 2-90 min. All active
      treatments produced significantly greater bronchodilation than placebo as early
      as 2 min after administration, and their peak effects within 10 min; and no
      significant differences were noted between them. Mean recovery times by 50% of
      the FEV1 decrement provoked by methacholine were significantly shorter for the
      active medications: 5.7 min (formoterol 24 micrograms), 6.4 min (salbutamol 400
      micrograms), 10.2 min (formoterol 12 micrograms), and 53.1 min (placebo); the
      respective times for recovery by 80% being 18.0, 17.4, 22.1, and 83.3 min. We
      conclude that single doses of the dry powder formulations of all three active
      treatments produce rapid and effective bronchodilation. This conclusion should
      not, however, be extrapolated to the regular use of these medications, since
      differential down-regulation and tachyphylaxis may then exert an influence.

PMID- 9160414
TI  - Differential inhibition by selective phosphodiesterase inhibitors of antigen,
      LTC4 and histamine-induced contraction of guinea-pig isolated trachea.
AB  - Antigen (ovalbumin)-induced contraction of guinea-pig isolated trachea, which
      largely resulted from the endogenous release of peptidoleukotrienes, was strongly
      inhibited by the non-selective phosphodiesterase (PDE) inhibitor theophylline
      and, more potently, by the selective PDE type IV inhibitors rolipram and Ro 20
      1724. It was also strongly inhibited by the PDE type V inhibitor zaprinast, but
      much less so by the PDE type III inhibitor siguazodan and milrinone. Similar
      results were obtained in trachea minus epithelium. In contrast to their effects
      vs. allergic airway smooth muscle contraction, both milrinone and siguazodan
      potently relaxed leukotriene C4 (LTC4)-induced contraction in isolated trachea
      from non-sensitized animals. In this assay, rolipram, Ro 20-1724 and zaprinast
      were less active compared to their effects vs. ovalbumin-induced contraction,
      whereas theophylline had equivalent potency in the two tests. The relative
      potencies of rolipram and siguazodan in relaxation of trachea were similar when
      added prior to or after either LTC4 or histamine. These results suggest that the
      higher potency of selective PDE type IV & V inhibitors compared with PDE type III
      inhibitors vs. ovalbumin-induced contraction is due to their greater inhibition
      of anaphylactic mediator release. The converse is true if we consider their
      bronchodilator actions, although the superior efficacy of selective PDE type III
      inhibitors over PDE type IV inhibitors may vary in sensitized vs. non-sensitized
      animals. The present results are in agreement with a previous study showing that
      low concentrations of a beta 2-agonist increased the relaxant effect of selective
      PDE type IV inhibitors in guinea-pig trachea. The present data indicate that
      prophylactic use of selective PDE type IV inhibitors combined with therapeutic
      use of low dose inhaled beta-agonist might represent an alternative to the use of
      antiallergic or steroid therapy in asthma.

PMID- 9160415
TI  - Effects of growth and breed on direct static measurements of chest wall
      compliance in cattle.
AB  - Chest wall compliance (CW) was measured in 59 conscious standing calves, aged six
      to 162 days, which were breathing air spontaneously through a face mask. The
      airways were occluded at the end of inspiration in order to elicit the Hering
      Breuer reflex, the effectiveness of which was ensured by the presence of a
      plateau on the tracings of airway opening and oesophageal pressure (Pes). CW was
      measured directly from the inspired volume of the occluded breath and changes in
      Pes generated by the recoil of the relaxed chest wall. This airway-occlusion
      technique yielded reproducible CW values similar to those measured by classical
      invasive methods. The ratio of CW to bodyweight in the growing calves (sCW)
      ranged from 2.2 to 11.5 ml cmH2O-1 kg-1 and was correlated negatively with age:
      (log sCW = 0.91-0.003 x age, r = 0.68), the rate of decline corresponding well to
      the multispecies allometric growth relationship.

PMID- 9160416
TI  - Development of persistent intestinal infection and excretion of Lawsonia
      intracellularis by piglets.
AB  - Challenge experiments using Lawsonia intracellularis as oral inocula have
      established its aetiological role in porcine proliferative enteropathy. Thirty
      piglets, in four groups, were weaned at 21 days of age and inoculated orally at
      24 days. Six piglets were challenged with 1.0 x 10(8) L intracellularis strain
      916/91 (NCTC 12657) passaged 12 times in vitro, six with 5.0 x 10(8) of the same
      strain, seven with 3.0 x 10(8) L intracellularis strain LR 189/5/83, passaged
      nine times, and 11 controls were dosed with sucrose-potassium glutamate buffer.
      An immunofluorescence assay for L intracellularis was applied to faecal smears
      and a polymerase chain reaction (PCR) incorporating L intracellularis-specific
      primers was applied to extracts of bacterial DNA derived from the faeces samples.
      Up to five pigs in each challenge group excreted detectable L intracellularis in
      faeces, in samples taken between two and 10 weeks after challenge. Some of the
      pigs had up to 7 x 10(8) L intracellularis g-1 faeces. The average weight gains
      of the higher dose challenge groups were moderately below those of the control
      pigs between three and nine weeks after challenge; diarrhoea was also observed in
      six pigs, two to four weeks after challenge. Numerous L intracellularis were
      detected in the intestines of all the pigs challenged with strain LR 189/5/83 and
      two of the pigs challenged with 916/91, but not in other tissues.

PMID- 9160417
TI  - Effect of allopurinol on the formation of reactive oxygen species during intense
      exercise in the horse.
AB  - Allopurinol was administered to six horses in a cross-over study to determine the
      relative contribution of xanthine oxidase (XO) activity to the formation of
      reactive oxygen species (ROS) in the horse during intense exercise. Exercise
      increased the mean (SEM) plasma lipid hydroperioxide concentration to a maximum
      of 492.7 (33.4) microM within one minute of exercise completion and maximum
      levels of both oxidised glutathione (GSSG) in haemolysates of red blood cells and
      the glutathione redox ratio (GRR) occurred 20 minutes after exercise (87.2 [12.2]
      microM and 8.9 [0.9] per cent, respectively). Allopurinol significantly reduced
      lipid hydroperoxides, GSSG and the GRR at the corresponding maximal times after
      exercise measured during control exercise (217.5 [32.1] microM. 63.8 [8.6] microM
      and 6.8 [0.7] per cent, respectively). Significantly higher levels of
      hypoxanthine and xanthine were measured after exercise in the plasma of horses
      that received allopurinol than in control horses, although uric acid levels
      remained constant. In control horses, plasma uric acid concentrations increased
      after exercise to a maximum 20 minutes after exercise of 28.1 (2.6) microM,
      significantly higher than in horses given allopurinol (9.6 [1.3] microM). The
      results show that the inhibition of XO by allopurinol leads to a decrease in the
      formation of ROS during exercise, and thus a reduction in oxidative stress.

PMID- 9160418
TI  - Differences in a ribosomal DNA sequence of lungworm species
      (Nematoda:Dictyocaulidae) from fallow deer, cattle, sheep and donkeys.
AB  - The second internal transcribed spacer (ITS2)* of the ribosomal DNA of
      Dictyocaulus viviparus from cattle, D eckerti from fallow deer. D filaria from
      sheep and D arnfieldi from donkeys has been sequenced to investigate the genetic
      relationships among lungworm species, especially between D viviparus and D
      eckerti, because the latter is not generally accepted as a separate species. The
      length of the ITS2 varied between 403 and 481 bases, and its GC content ranged
      from 25 to 33 per cent. Intraspecific variations in D viviparus (0 to 1.5 per
      cent) and D eckerti (0.6 to 3.3 per cent) were slight; sequence homology between
      the species ranged from 50.3 to 76.7 per cent. Some sequence differences occurred
      at restriction sites of endonucleases leading to characteristic restriction
      fragment length patterns. The interspecific differences between D viviparus and D
      eckerti far exceeded the intraspecific variation, thus providing additional
      evidence that the two species are genetically distinct.

PMID- 9160419
TI  - Epidemiological analysis of Malassezia pachydermatis isolates by partial
      sequencing of the large subunit ribosomal RNA.
AB  - The opportunistic yeast Malassezia pachydermatis is commonly recovered from both
      normal and diseased skin of warm-blooded animals. The diversity of M
      pachydermatis isolates obtained from a wide range of hosts was investigated by
      the partial sequencing of the large subunit (LSU) ribosomal RNA. Among 100
      isolates examined, seven types (Ia-Ig) were discriminated on the basis of
      nucleotide sequence diversity. The seven types differed by one to five mutations,
      all of them corresponding to transitions. The predominant sequence, type Ia,
      appeared to be ubiquitous since it was observed in isolates recovered from
      domestic and wild carnivora, from a monkey and from man. In contrast the sequence
      types Ic, Id and Ig seemed to be more host-specific; they included isolates
      recovered exclusively from rhinoceros, dogs and ferrets, respectively. None of
      the seven sequence types correlated with isolation from healthy skin or a
      particular lesion (otitis externa or other dermatitis). The study indicated that
      the skin of an animal may be colonised by more than one type of M pachydermatis.

PMID- 9160420
TI  - Radionuclide imaging of abomasal emptying in sheep.
AB  - A liquid radionuclide tracer was administered to nine sheep in order to visualise
      the abomasum with a gamma camera computer system. The aim was to develop a method
      of studying gastric emptying, with minimal surgical intervention. Oral
      administration of the tracer gave good images of the whole complex stomach, but
      quantifying abomasal emptying was not possible because of the superimposition of
      the stomach compartments. When the reticular groove reflex was stimulated with
      oral copper sulphate the radionuclide bypassed the reticulorumen, allowing
      quantitative analysis of abomasal activity. However, the repeatability of the
      reflex activation was low. Radionuclide administered directly into the abomasum
      produced good images of abomasal outflow and provided digital data which were
      analysed quantitatively. A wide range of emptying rates was observed, generally
      with a stepped pattern.

PMID- 9160421
TI  - Method for the growth of equine airway epithelial cells in culture.
AB  - A serum-free cell culture method was developed for equine tracheal epithelial
      cells which allowed the growth and characterisation of the phenotypical
      properties of this cell type. Several variables influenced the efficacy of the
      attachment and growth of the isolated cells. Serum and a collagen matrix were
      essential components for efficient cell attachment. Once attachment had occurred,
      cell growth was enhanced by a serum-free medium containing bovine pituitary
      extract, retinoic acid, insulin, hydrocortisone, transferrin, epidermal growth
      factor, adrenaline and triiodothyronine. The mean time taken for the cells to
      grow to confluency varied from 12.6 to 28.0 days, depending on the medium used.
      Collagen matrix was essential to aid the proliferation of the cells.

PMID- 9160422
TI  - Effects of sex and age on the ossification of the collateral cartilages of the
      distal phalanx of the Finnhorse and the relationships between ossification and
      body size and type of horse.
AB  - The ossification of the collateral cartilages of the distal phalanx was evaluated
      in dorsopalmar radiographs of the front feet of 202 Finnhorses (101 females and
      101 males, aged six months to 20 years) with reference to the sex, age, body
      measurements and type of horse. Ossification was more common and more extensive
      in females than in males from about two years of age. In females, the lateral
      cartilages were significantly more ossified than the medial cartilages; in males,
      ossification was more symmetrical in the cartilages of each foot. The amount of
      ossification increased rapidly during the second and third years of life, and
      more slowly in adults. The low positive correlation coefficients between
      ossification and different body measurements of the horse suggested that there
      was more ossification in large horses, and the correlation between chest-width in
      adults and the extent of ossification was statistically significant. The working
      type of horses showed slightly more ossification than trotters and riding horses.
      Ossification variables, which included ossification at both the base of the
      cartilage and at the possible separate centres of ossification (total
      ossification of individual cartilages and "possibly significant' ossification in
      the front feet), were found to be most satisfactory for expressing the extent of
      ossification.

PMID- 9160423
TI  - Proteoglycan metabolism of equine articular chondrocytes cultured in alginate
      beads.
AB  - Equine chondrocytes were cultured in vitro for 30 days in ionically gelled
      alginate beads. The alginate polymerises into a stable gel in the presence of
      divalent cations (calcium), and rapid depolymerisation in the presence of a
      calcium chelator releases the viable chondrocytes. The chondrocytes maintained a
      spherical appearance for 30 days in culture, in marked contrast to monolayer
      cultures, which develop a dedifferentiated fibroblastic morphology. The major
      proteoglycan molecule produced by the encapsulated chondrocytes was aggrecan, of
      similar hydrodynamic size to aggrecan molecules present in the matrix of the
      articular cartilage from which the cells were harvested. Link protein, keratan
      sulphate and chondroitin sulphate were also synthesised by the chondrocytes, as
      demonstrated by immunohistochemistry. The proteoglycan secreted by the
      chondrocytes consisted of at least two pools, one remaining adjacent to the cell
      and forming a dense, cell-associated matrix, and another migrating more
      peripherally into the intercellular compartment. Newly synthesised proteoglycans
      extracted from the pericellular matrix and the intercellular matrix were similar
      in hydrodynamic size and aggregated in the presence of exogenous hyaluronan.

PMID- 9160425
TI  - Development and characterisation of a model of bovine inflammation.
AB  - Two dialysis sacs each containing 50 ml dextran sulphate solution were implanted
      into the peritoneal cavities of five three month-old calves. One sac was
      inoculated with Pasteurella haemolytica or Streptococcus uberis and the second
      sac served as an uninoculated control. Samples of sac fluid removed after 0,
      four, six, eight, 15, 24, 36 and 48 hours and then at 24 hour intervals after
      inoculation revealed bacterial growth up to 9.0 log10 cfu ml-1 by two to three
      days after inoculation. Concentrations of 25 to 48 ng ml-1 of the inflammatory
      mediator prostaglandin E2 (PGE2) were detected six to 96 hours after inoculation,
      similar amounts being generated in sacs inoculated with either bacterium, but the
      concentrations in control sacs remained below 10 ng ml-4 over the seven day
      experiment. Post mortem, a tissue cast invested each of the inoculated sacs.
      Histologically, the reaction was an acute inflammatory response similar to that
      evoked by each bacterium in the target organ.

PMID- 9160424
TI  - Pharmacokinetics of tilmicosin in serum and milk of goats.
AB  - Tilmicosin was administered to goats intravenously and subcutaneously to
      determine its concentration in blood and milk and its kinetic behaviour. After a
      slow intravenous injection, the serum concentration-time curve indicated a two
      compartment open model with a mean (SEM) elimination half-life (t1/2 beta S) of
      4.36 (0.04) hours. After a subcutaneous injection the drug was eliminated more
      slowly from serum and milk, with t1/2 beta S of 29.3 and 41.4 hours,
      respectively. The apparent volume of distribution of tilmicosin was more than 1
      litre kg-1. The peak serum tilmicosin concentration was 1.56 micrograms ml-1 6.39
      hours after a subcutaneous injection of 10 mg kg-1. Tilmicosin was extensively
      secreted into milk, reaching a maximum concentration of 11.6 micrograms ml-1 and
      having a large AUCmilk/AUCserum ratio of approximately 12:1. Tilmicosin was
      detectable in milk for 11 days after a single subcutaneous dose.

PMID- 9160426
TI  - The concentration of creatine in meat, offal and commercial dog food.
AB  - The concentrations of creatine (Cr), phosphorylcreatine (PCr) and creatinine (Cn)
      were determined in a variety of meats, before and after cooking by boiling, in a
      range of commercially available canned dog foods, in rendered and dried meat
      products and in commercially available dry dog foods. None of the samples
      contained PCr. Uncooked chicken, beef and rabbit meat contained approximately 30
      mmol kg-1 of Cr. Ox-heart and ox-liver had Cr concentrations of 22.5 and 2.3 mmol
      kg-1, respectively. Canned dog foods had Cr concentrations of 0.5 to 2 mmol kg-1.
      Dried meat samples had Cr concentrations of 90 to 100 mmol kg-1 dry weight. In
      contrast, the Cr concentration of dried rendered meat meal was 3 mmol kg-1 dry
      weight or less. Dry dog foods contained 0.5 to 4 mmol kg-1 dry weight of Cr. The
      results indicate that in the canned dog foods, the dried meat samples and the
      dried rendered meat meal creatine had been degraded to variable extents to
      creatinine.

PMID- 9160427
TI  - Accumulation of leucocytes and cytokines in the lactating ovine udder during
      mastitis due to Staphylococcus aureus and Escherichia coli.
AB  - The accumulation of leucocytes in milk and in teat cistern tissues, and the
      presence of the cytokines interleukin-1 beta (IL-1 beta), tumour necrosis factor
      alpha (TNF-alpha), interleukin-8 (IL-8), granulocyte-macrophage colony
      stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) in milk was studied
      during inflammation in the lactating ovine udder induced by Staphylococcus aureus
      and Escherichia coli. Milk and/or teat tissue samples were taken before and four,
      eight and 24 hours after inoculation. Both S aureus and E coli induced a
      significant accumulation of leucocytes in milk, S aureus from eight hours with a
      peak after 24 hours, and E coli from four hours, with a peak after eight hours.
      After the inoculation of S aureus the numbers of subepithelial neutrophils in the
      teat cistern tissues were increased after four hours and had increased further by
      eight hours. After the inoculation of E coli, tissue neutrophil numbers peaked at
      four hours and were still high at eight hours. Large numbers of S aureus were
      recovered from milk throughout the experiments whereas the recovery of E coli
      diminished over time. TNF-alpha, IL-8 and IL-1 beta were detected in milk during
      the inflammation, and low levels of GM-CSF and IFN-gamma were also observed
      occasionally. Of the cytokines measured, TNF-alpha and IL-8 reached the highest
      concentrations, accumulating in a similar pattern to the leucocytes for both
      infections. IL-1 beta was detected mainly during S aureus-induced inflammation,
      indicating differences in the inflammatory responses elicited by the organisms.

PMID- 9160428
TI  - Relationships between the bone pathologies, ash and mineral content of long bones
      in 35-day-old broiler chickens.
AB  - Histological examinations and estimations of the contents of ash, phosphorus and
      calcium were used to investigate the femora and tibiotarsi from lame and normal
      35-day-old broilers from Holland, Northern Ireland and Scotland. The prevalence
      of different pathologies varied with the source of the broilers and there were
      correlations between histological and bone ash values. The most common condition
      causing lameness was bacterial infection within the physis and cartilaginous
      epiphysis (bacterial chondronecrosis) of the proximal tibiotarsus, and there was
      a possible link between rickets attributable to a relative phosphorus deficiency
      and this condition. There were wide variations between birds in the cortical bone
      quality as assessed histologically and by estimates of the bone ash content and
      phosphorus to calcium ratios. Theses variations may be related to different
      probabilities of bone fracture.

PMID- 9160429
TI  - Phagocytosis of Streptococcus uberis by bovine mammary gland macrophages.
AB  - The ability of macrophages isolated from the bovine mammary gland to phagocytose
      and kill Streptococcus uberis was investigated. The strains of S uberis used were
      selected on the basis of their known resistance (C197C) or sensitivity (EF20) to
      phagocytosis by bovine peripheral blood neutrophils in the same assay system.
      Macrophages isolated from mammary secretions collected during the mid-dry period
      were capable of phagocytosing both strains of S uberis in the presence of serum
      and skimmed milk. The removal of complement from serum by heat-inactivation did
      not influence the opsonization of S uberis for phagocytosis by mammary
      macrophages and both IgG1 and IgG2 isotypes were found to opsonise both strains.
      The uptake of S uberis into the cells was confirmed by electron microscopy.
      Potential mechanisms by which S uberis could resist phagocytosis by neutrophils
      but not by macrophages are discussed.

PMID- 9160430
TI  - Differences in patterns of meningoencephalitis due to bacterial kidney disease in
      farmed Atlantic and chinook salmon.
AB  - A range of neural pathology, in particular meningitis with sporadic encephalitic
      extension, can develop in salmonids infected with Renibacterium salmoninarum, the
      agent of bacterial kidney disease (BKD). Tissues from 134 Atlantic salmon and 164
      chinook salmon were selected on the basis of their having a positive diagnosis of
      BKD, with evidence of multi-tissue infection including the brain (214 fish), or
      brain involvement in the absence of systemic lesions attributable to BKD (58
      fish). Although meningitis was a feature of BKD in both species, encephalitis was
      more common in the Atlantic salmon. Specifically, a higher portion of the
      Atlantic salmon had encephalitis accompanying meningitis (P = 0.0159),
      encephalitis in the absence of meningitis (P = 0.0756), and brain lesions
      (meningitis or encephalitis) in the apparent absence of systemic lesions (P =
      0.0067). These findings suggest either that some aspects of the pathobiology of R
      salmoninarum are dictated by the host species, or that the farm management
      methods used to deal with BKD are sufficiently different for the two species of
      salmon that they affect the pathology of the disease.

PMID- 9160431
TI  - Effect of doses of protected polyunsaturated fatty acids on indicators of
      selenium status of sheep.
AB  - In monogastric animals, dietary polyunsaturated fatty acids (PUFA) have been
      shown to increase glutathione peroxidase (GSH-Px) activity in plasma and
      erythrocytes and to decrease plasma selenium concentration. Ruminants feeding on
      grass can have a high intake of PUFA. In this experiment, sheep were dosed orally
      with protected PUFA (Pr-PUFA) for five weeks at 5 g kg liveweight-1 three times
      per week for the first week and at 8 g kg-1 for the following four weeks. The Pr
      PUFA did not affect GSHPx activity in erythrocytes or plasma or liver selenium
      concentration, but did reduce the selenium concentration in muscles by between 20
      and 30 per cent. In addition, liver iron concentration was reduced by about 42
      per cent. The results suggest that dietary PUFA may affect the distribution of
      selenium rather than its absorption.

PMID- 9160432
TI  - Analysis and significance of anti-nuclear antibodies in dogs.
AB  - Assays for detecting and measuring antinuclear antibodies (ANA) in dogs were
      compared. They included the indirect immunofluorescence test, using rat liver as
      substrate, and ELISAs for three nuclear antigens: double-stranded DNA, single
      stranded DNA, and histone. There was no correlation between the ANA titre and
      antibodies to the three nuclear antigens. Analysis of ANA in different
      arthropathies showed no specific disease association. HEP-2 cells showed no
      fluorescence reaction with either ANA-positive or ANA-negative dog sera. Western
      blotting produced too complex a pattern to identify specific antigens. The
      antigens that reacted with ANA in dogs were not identified; there is either a
      broad range of reactivities or non-specific binding of immunoglobulins.

PMID- 9160433
TI  - Changes in glucose transport activities in mammary adenocarcinoma of dogs.
AB  - The activities of D-glucose transport (D-GT) and cytosolic enzymes were
      significantly higher in mammary adenocarcinoma of dogs than in mammary gland from
      normal dogs. The activities of D-GT in adenocarcinoma were over three-and-a-half
      times higher than in the controls. The K(m) value of the D-GT activity for
      glucose in both the adenocarcinoma and normal mammary gland was approximately 0.9
      mM. The activities of the key glycolytic enzymes, hexokinase and pyruvate kinase,
      in the adenocarcinoma were also more than three-and-a-half times higher than in
      the controls. The increased activities of D-GT are considered to be accompanied
      by an acceleration of glucose utilisation in the adenocarcinoma of dogs.

PMID- 9160434
TI  - Solid state production of a Mucor bacilliformis acid protease.
AB  - Acid protease production by a local strain of Mucor bacilliformis was performed
      by solid state cultivation on different agricultural by-products as substrate.
      The effects of different parameters on enzyme biosynthesis were studied: Wheat
      bran wetted at 120% with a 200 mM HCl solution and inoculated with 5 x 10(5)
      spores/g produced a milk clotting activity of 7500 U/g bran after 72 h
      cultivation at 24 degrees C.

PMID- 9160435
TI  - Disclosure practices and cultural narratives: understanding concealment and
      silence around cancer in Tuscany, Italy.
AB  - Disclosure practices are embedded in and enact personal, professional, and
      societal narratives. These narratives are not given but contested and evolving.
      The medical arena constitutes an important social space in which this
      contestation, reproduction and change take place. More specifically, based on
      ethnographic and cultural survey data, we describe and interpret the cultural
      sense of "not telling" about cancer within the local world of Tuscany, Italy. We
      locate the traditional practice of non-disclosure of cancer diagnoses within a
      larger cultural narrative we call "social-embeddeness", a narrative of social
      unity and hierarchy, of protection from or adaptation to the inevitable
      necessities of life, in part by using narrative itself to construct a sense of
      group protection. This narrative is being challenged, as it confronts other
      medical and societal narratives, such as one originating from the United States
      and embedded in health care practices like open disclosure, informed consent,
      Advanced Directives, and the Patient Self-Determination Act, what we call the
      "autonomy-control narrative". Explicit disclosure to a patient about his or her
      illness and the future plays an important role in actualizing this narrative, in
      helping in the quest to control one's destiny, eliminate uncertainty and
      necessity, and foster a person's identity as singular and sovereign over
      him/herself. The concept "narrative" highlights the ideology and intent of
      people's practices, not just "outcome", and helps us understand contradictions in
      various disclosure contexts as partly due to multiple cultural narratives in
      play. Considering some of the practices and understandings embedded within and
      reproduced by the larger cultural narratives also allows us to track the dynamics
      of history and individual biography, to locate and compare approaches to
      disclosure across time and space, and to avoid the pitfalls of cultural
      determinism and cultural stereotypes.

PMID- 9160436
TI  - Designing educational messages to improve weaning food hygiene practices of
      families living in poverty.
AB  - This paper describes a methodology to design feasible interventions to improve
      weaning food hygiene practices of families living in extreme poverty. Educational
      messages to promote specific behavioural changes were defined and tested by
      utilizing a combination of ethnographic, survey and observational methods, and
      integrating viewpoints and suggestions of mothers and caretakers into the
      decision-making process. This new approach culminated in a household trial in
      which five groups, each of 15 non-practising mothers, were invited to adopt
      defined behaviours (handwashing before and after defined events, boiling water
      for reconstituting powdered milk, feeding gruel by spoon rather than
      bottlefeeding, not storing gruels and milks, and all four together). All
      initiated the advocated behaviours and most (53-80%) sustained the new behaviours
      and practised them every time during a one-month period. Of the four advocated
      behaviours, spoon-feeding was the most difficult to adopt wholly. The methodology
      was developed in response to the high priority given to reducing weaning food
      contamination for diarrhoeal disease control, and the lack of any existing
      methodology for defining appropriate educational interventions in resource-poor
      regions. This approach, with its combination of qualitative and quantitative
      methods and community focus, is recommended for future studies to design hygiene
      and other health education interventions in developing countries.

PMID- 9160437
TI  - A change of heart and a change of mind? Technology and the redefinition of death
      in 1968.
AB  - In 1968, an ad hoc committee of Harvard faculty publicly redefined death as
      "brain death". What interests and issues compelled the redefinition of death, and
      formed the "spirit" of this precedent-setting policy? This paper reports on an
      historical study of the files of the Harvard ad hoc committee, the proceedings of
      an international conference on ethical issues in organ transplantation, and a
      review of the medical literature and media in the decades preceding the
      redefinition of death. This analysis of the technological and professional forces
      involved in the redefinition of death in 1968 questions two common theses: that
      technological "progress", primarily in the areas of life support and
      electroencephalography, literally created brain-dead bodies and dictated their
      defining features (respectively), and that Harvard's definition of brain death by
      committee constituted a net loss of autonomy for medicine. In fact, medical
      researchers through the 1960s disputed and negotiated many features of the brain
      death syndrome, and transplantation interests-perhaps more kidney than heart
      played a particularly influential role in tailoring the final criteria put forth
      by Harvard in 1968. It is also doubtful whether Harvard's definition of brain
      death by multidisciplinary committee undermined medical privilege and autonomy.
      The Harvard Ad Hoc Committee may not have succeeded in establishing definitive,
      indisputable brain death criteria and ensuring their consistent application to
      all clinical cases of brain death. However, it did gain significant ground for
      transplant and other medical interests by (1) establishing brain death as a
      technical "fact" and the definition of brain death as an exercise for medical
      theorists, (2) involving non-medical ethics and humanities experts in supporting
      the technical redefinition of death, and, (3) successfully involving transplant
      surgeons in the redefinition of death and attempting (albeit unsuccessfully) not
      to exclude them from the actual diagnosis of death in individual cases.

PMID- 9160438
TI  - Age, adjustment, and costs: a study of chronic illnesses.
AB  - Much concern has been expressed about increasing health costs associated with an
      aging population. In relation to chronic conditions, this study demonstrates that
      cost seems to be a function of adjustment to the chronic condition rather than of
      age in and of itself. We know from previous work that people with poor
      psychosocial adjustment cost considerably more than do people who are either
      moderately or well adjusted and this study shows that older, poorly adjusted
      persons are no more costly than their younger counterparts.

PMID- 9160439
TI  - Surrogate assessment of coronary artery disease patients' functional capacity.
AB  - An investigation of the surrogate assessment of coronary artery disease (CAD)
      patients' functional capacity was conducted using 193 patient and surrogate rater
      dyads. Mean age of patients and surrogate raters were 60.4 and 54.4 years,
      respectively. Patients and surrogates independently completed a brief
      questionnaire that assessed health and psychosocial factors. The Duke Activity
      Status Index (DASI) was contained in the patients' questionnaire, while a similar
      form modified to assess patients' functional capacity was imbedded in the
      surrogates' questionnaire. Results indicated similar psychometric characteristics
      and clinical validity for patients' self-report and surrogates' ratings,
      suggesting that the Surrogate Rating Form of the Duke Activity Status Index (DASI
      SRF) is a reliable and valid proxy method of assessing patient's functional
      capacity when this information may not be obtained directly from the patient.
      Further, while there were no effects of surrogates' health and psychological
      characteristics on their ratings of patients' functional capacity, in comparison
      with other surrogates, spouses were more likely to rate patients higher in
      functional capacity. Exploration of the patient/care provider relationship via
      concurrent use of the DASI and DASI-SRF is discussed.

PMID- 9160440
TI  - Beyond single indicators of social networks: a LISREL analysis of social ties
      among the elderly.
AB  - While the health promoting influences of social networks have been shown in a
      number of studies, little attention has been paid to measurement issues within
      the field of epidemiology. The purpose of this paper is to propose a new set of
      measures of social networks for use in epidemiological research on the elderly.
      We use confirmatory factor analysis to test a multidimensional model of social
      networks using data from a large epidemiologic study of community-dwelling adults
      age 65 and over (U.S.A.). Confirmatory factor analysis conducted using LISREL
      showed that our model provides a good fit to the data after several adjustments
      for correlated measurement error were introduced. Based on this analysis, we
      developed new measures of four dimensions and a summary index of social networks.
      Bivariate relationships between our new measures and several sociodemographic
      variables of interest are also presented.

PMID- 9160441
TI  - Mapping visual analogue scale health state valuations onto standard gamble and
      time trade-off values.
AB  - Despite becoming increasingly common in evaluations of health care, different
      methods of quantitatively measuring health status appear to produce different
      valuations for identical descriptions of health. This paper reports on a study
      that elicited health state valuations from the general public using three
      different methods: the visual analogue scale (VAS), the standard gamble (SG) and
      the time trade-off (TTO). Two variants of the SG and TTO were tested: Props
      (using specially designed boards and cards); and No Props (using a self
      completion booklet). This paper focuses on empirical relationships between health
      state valuations from the VAS and the (four) other methods. The relationships
      were estimated using Tobit regression of individual-level data. In contrast to a
      priori expectations, the mapping functions estimated suggest that differences are
      more pronounced across variant than across method. Furthermore, relationships
      with VAS scores are found to depend on the severity of the state: TTO Props
      valuations are higher than VAS responses for mild states and lower for more
      severe states; SG Props valuations are broadly similar to VAS scores over a wide
      range; and No Props responses are consistently higher than VAS valuations,
      particularly for more severe states. Explanations are proposed for these
      findings.

PMID- 9160442
TI  - Patient preference for genders of health professionals.
AB  - Preferences for physicians' gender is an obvious and well documented example of
      considerations of patients' attitudes. But research carried out in this field is
      rather limited to the domain of family medicine. This article describes
      preferences for 13 different health professions: surgeons, neurologists,
      anaesthetists, internists, general practitioners, psychiatrists, psychologists,
      social workers, hospital and district nurses, home helps, gynaecologists and
      midwives. Our investigation also concerns the reasons for people's preferences.
      In February 1993 a self-administered survey was completed and returned by 961 out
      of 1113 (response 86%) participants of the Dutch Health Care Consumers Panel, a
      panel resulting from a random sample of Dutch households. On a range of different
      health professions a varying minority of patients prefer a care provider of a
      particular gender. There are virtually no sex preferences for the more
      "instrumental" health professions (e.g. surgeons, anaesthetists). Gender
      preferences are stronger for those health professions more likely engaged in
      intimate and psychosocial health problems (e.g. gynaecologists and GPs).
      Preferences expressed do not relate to sex stereotypes of gender differences in
      instrumentality, expertise, efficiency, consultation length, and personal
      interest. The majority of persons who prefer female health professionals indicate
      that they talk more easily to females than to males, and feel more at ease during
      (internal) examination by females than by males. Persons who prefer male health
      professionals use the same reasons in favour of males. The discussion relates to
      gender differences in the communication style of male and female physicians.

PMID- 9160443
TI  - Women's health care: for whom and why?
AB  - Differences are investigated between female practice populations of female
      general practitioners providing women's health care and of women and men general
      practitioners providing regular health care. Women's health care in the
      Netherlands is provided in the general practice "Aletta" and is based on the
      following principles: (1) consideration of the patient's gender identity and
      gender roles; (2) consideration of the patient's personal and social situation;
      (3) treating the patient respectfully; (4) encouraging the patient to cope with
      health problems and stimulating self-responsibility; and (5) avoidance of
      medicalization. Data were derived from an extensive health interview with 253
      women Aletta patients (15 years or older) about socio-demographic
      characteristics, gender role, attitudes, somatic and mental health status, and
      medical consumption. The Aletta patients were also asked about their motives in
      choosing women's health care. Reference groups were comprised of 391 and 628
      women patients of women and men general practitioners, respectively, providing
      regular health care. Logistic regression analyses were performed to explain
      differences between the three groups. "The Aletta patient" can be characterized
      as a young, urban, single, highly educated, working, and childless woman, who
      deliberately chooses women's health care. She is more androgynous than women of
      other doctors, less inclined to seek help with the GP, she suffers more from
      psychosomatic and psychosocial problems, and she has poorer mental health. It
      results in a higher use of mental health care, and also of alternative health
      care. Women patients of women and men doctors providing regular health care
      hardly differ between each other in the characteristics described above. Health
      policy makers should take into consideration that in the future possibly more
      women will prefer health care in which the ideas of women's health care are being
      applied. The integration of some important aspects of women's health care into
      regular health care is recommended.

PMID- 9160445
TI  - Introduction to symposium: on-going studies in critical medical anthropology.

PMID- 9160444
TI  - Patterns of sexual behaviour in a rural population in north-western Tanzania.
AB  - The HIV epidemic in sub-Saharan Africa has been characterised by the predominance
      of heterosexual transmission. Patterns of sexual behaviour have been implicated
      in the spread of the epidemic, but few quantitative data are available on sexual
      behaviour in rural populations in Africa. This paper reports data from a survey
      of 1117 adults aged 15-54 years selected randomly from twelve rural communities
      in Mwanza Region, Tanzania. Sexual debut occurred early, 50% of women and 46% of
      men reporting first sex before age 16. On average, women married 1.8 years and
      men 6.1 years after their sexual debut. In women, age at sexual debut appears to
      have increased over time, in parallel with an increase in age at first marriage.
      Men were generally married later, to women around five to ten years younger than
      themselves. Marital dissolution and remarriage were common in both sexes.
      Reported numbers of sexual partners were compared with those recorded in a
      population survey in Britain. More men reported 10 or more lifetime partners, or
      three or more partners in the past year, in rural Mwanza (48% and 29%) than in
      Britain (24% and 6%). Women reported fewer partners, and results were broadly
      similar to British data. Casual sex during the past year was reported by 53% of
      the men and 15% of the women, but only 2% of men reported sexual contact with bar
      girls or commercial sex workers. Only 20% of men and 3% of women had ever used a
      condom. Interventions are needed to reduce the high levels of sexual partner
      change and casual sex, and low levels of condom use, recorded in this rural
      population. Targeting of interventions to traditional "core groups" may be of
      limited value in rural areas, and additional strategies are needed, focusing
      particularly on teenagers who are at high risk of HIV and other sexually
      transmitted diseases.

PMID- 9160446
TI  - The misconstruction of critical medical anthropology: a response to a cultural
      constructivist critique.
AB  - Since its emergence over a decade ago as a distinct theoretical framework,
      critical medical anthropology (CMA) has engaged in debate and dialogue with
      various other perspectives within medical anthropology, particularly clinical
      anthropology, medical ecology, and, to a lesser degree, postmodernism. While at
      least two genres of CMA have emerged, both of which are involved in a dialogue
      with each other, proponents of other perspectives often misread or "misconstruct"
      the agenda of CMA as both a theoretical framework and a strategy for health
      activism. This essay in particular critiques this process among proponents of the
      interpretative or cultural constructivist perspective. On a positive note,
      however, I urge critical medical anthropologists and cultural constructivists
      within medical anthropology to enter into a dialogue with each other because
      their two perspectives, despite the presence of obvious epistemological
      differences, share commonalities.

PMID- 9160447
TI  - Constructing a complex of contagion: the perceptions of AIDS among working
      prostitutes in Costa Rica.
AB  - This paper explores the perceptions of HIV/AIDS held by a group of women working
      as prostitutes in San Jose, Costa Rica. Adopting the theoretical perspective of
      critical medical anthropology, the analysis of the prostitutes' constructions of
      HIV/AIDS is linked to the political and historical context of power that
      constitutes a medical cultural hegemony. The way in which the research
      participants associate threats of HIV/AIDS with violence to create a complex of
      contagion that both perpetuates and challenges the hegemonic model of disease is
      discussed. Specifically, biomedicine's designation of the prostitute as the
      "vector" of disease is contrasted with the position that the prostitutes create
      for themselves. Through a critical analysis of this complex of contagion,
      oppressive power structures come into sharp focus.

PMID- 9160448
TI  - Hard lives and evil winds: illness aetiology and the search for healing amongst
      Ciskeian villagers.
AB  - This paper examines the explanations for illness used by Ciskeian villagers to
      account for conditions ranging from diarrhoea and tuberculosis to anxiety and
      hypertension. Explanations recognise the links between illness and hard physical
      labour, poor working conditions and poverty whilst also acknowledging
      supernatural grounds for affliction. The healing resources available to
      villagers, which are outlined here, include state-run health facilities, a large
      number of private biomedical practitioners, a variety of indigenous therapists
      including religious healers-and a store of common knowledge. In keeping with
      recent developments within critical medical anthropology, this paper seeks to
      analyse illness aetiology and health seeking behaviour within the broad social
      and economic context of individual lives. In Ciskei, one of South Africa's former
      nominally independent homelands, that context includes high levels of
      unemployment, dependence on migrant labour earnings and on welfare payments, lack
      of infrastructure such as water supply and transportation and a significant
      degree of economic differentiation between households. Against this backdrop,
      individual case studies will be examined which will illustrate how degrees of
      powerlessness and lack of disposable income affect both explanations of illness
      causation and health seeking behaviour among Ciskeian villagers.

PMID- 9160449
TI  - International Standards for Neurological and Functional Classification of Spinal
      Cord Injury. American Spinal Injury Association.

PMID- 9160450
TI  - Neurological issues.
AB  - The case histories of two patients who had had a spinal cord injury (SCI) were
      selected by the senior author and sent to four experts in the field of SCI. Based
      on the 1992 American Spinal Injury Association (ASIA) and International Medical
      Society of Paraplegia (IMSOP) standards, the four participants plus the senior
      author recorded the motor and sensory scores, the ASIA impairment scale (AIS),
      the neurological level (NL) and the zone of partial preservation (ZPP). Several
      minor scoring errors occurred among the participants, especially with motor
      scores when key muscles could not be tested due to pain, or external
      immobilization devices. Difficulties with interpretation occurred with the motor
      levels and the ZPP for the patient with a complete injury. This exercise points
      to the need for all examiners of SCI patients to thoroughly familiarize
      themselves with the standards and to use the motor and sensory scores to arrive
      at a NL and ZPP. They also indicate a need to revise the standards to clarify the
      determination of sensory levels and how to score muscles whose strength is
      inhibited by pain.

PMID- 9160451
TI  - Urethral cultures in female patients with a spinal cord injury.
AB  - Quantitative cultures of the urethral meatus were obtained from women with SCI
      undergoing intermittent catheterization. When compared with the urethral cultures
      of a group of female subjects, women with SCI had a greater number of isolates of
      Klebsiella pneumonia and Pseudomonas aeruginosa in the urethral flora. However
      there was not a significantly greater number of isolates or log numbers of E.
      coli or Enterococcus sp. in the urethral flora. The E. coli and Enterococcus sp.
      isolated from the urine were not isolated from the urethra of female patients
      with SCI in one third of the patients. This poor correlation between the
      simultaneous urethral and urine cultures of female subjects with SCI may reflect
      colonization of the urine with organisms that were unable to adhere to the mucosa
      and colonize the urethra. To what extent these organisms colonize or are
      temporary residents may be important in the pathogenicity of the infection.

PMID- 9160452
TI  - Four year experience with the AO Anterior Thoracolumbar Locking Plate.
AB  - For decades spinal surgeons have attempted to design simple, single stage
      anterior internal fixation systems for the thoracic and lumbar spine. Early
      devices presented both biomechanical and technical problems. The AO Anterior
      Thoracolumbar Locking Plate (ATLP) was designed to solve some of the problems
      encountered with early anterior instrumentation. The ATLP system is constructed
      in Commercially Pure titanium. It is a low profile device indicated for use for
      unstable burst fractures in the anterior column; metastatic tumor management; and
      degenerative diseases of the thoracolumbar spine between levels T10 and L5.
      Implantation of the device involves direct anterior decompression with sagittal
      reduction and corpectomy. This is followed by grafting reconstruction, and plate
      fixation. This device has been implanted in 25 patients with an average follow-up
      of 38 months. There were five (5) broken screws in three (3) patients, and no
      broken plates. Implant related postoperative complications included two misplaced
      screws. Preliminary results indicate that the ATLP system seems to be a safe, low
      profile, MRI/CT compatible device that provides definitive single stage fixation
      of the anterior spinal column.

PMID- 9160453
TI  - Relationships of oxygen uptake, heart rate, and ratings of perceived exertion in
      persons with paraplegia during functional neuromuscular stimulation assisted
      ambulation.
AB  - Previous reports have described significant limitations in the daily use of
      functional neuromuscular stimulation (FNS) ambulation systems by persons with
      spinal cord injuries (SCI). The potential application of these devices to provide
      physiological benefits as an exercise modality has prompted a reconsideration of
      the technology. However, the acute physiological effects related to the use of
      FNS systems have not been thoroughly examined. The purpose of this study was to
      investigate the relationships of oxygen consumption (VO2), heart rate (HR), and
      ratings of perceived exertion (RPE) during FNS ambulation by persons with SCI
      paraplegia. Eleven persons with thoracic level paraplegia, aged 21.5 to 38.0
      years, participated in an incremental FNS ambulation test. Metabolic measures
      were collected continuously via open circuit spirometry as the subjects performed
      a series of ambulation passes of progressively increasing pace. At the end of
      each ambulation pass, HR and RPE measures were collected. The test was terminated
      when either the subjects judged the effort to be maximal or when the
      investigators deemed the effort to be maximal based on HR. A strong linear
      relationship was documented between the VO2 and HR measures of all subjects
      throughout subpeak levels of FNS ambulation. RPE did not vary proportionally with
      VO2 until relatively high levels of exercise intensity were reached. This study
      indicates that HR, but not RPE, is an appropriate indicator of exercise intensity
      for persons with SCI paraplegia using a FNS ambulation system.

PMID- 9160454
TI  - Cough in spinal cord injured patients: the relationship between motor level and
      peak expiratory flow.
AB  - Pulmonary complications remain a major cause of morbidity and mortality in
      patients with higher level spinal cord injury. Neurologically intact individuals
      can cough in order to clear their air passage of lung secretions and foreign
      material. Patients with higher level cord injuries, with paralysis of the trunk
      and abdominal muscles, may not have the ability to generate an effective cough.
      If coughing is dependent on a caregiver, these patients will cough with reduced
      frequency. Because the innervation to the muscles involved in cough consists of
      nerves that arise from varying levels of the spinal cord, some patients with
      spinal cord injury have partial control over these muscles and thus can cough,
      though with reduced efficacy. Two hundred patients with varying levels of spinal
      cord injury were studied to determine if motor level and cough ability are
      correlated. Cough efficacy was measured using a peak expiratory flowmeter while
      patients were seated at 90 degrees. We concluded that there is indeed a direct
      relationship between motor level and peak expiratory flow produced during
      coughing.

PMID- 9160455
TI  - Postural hypotension and abnormalities of salt and water metabolism in myelopathy
      patients.
AB  - To describe the clinical manifestations of postural hypotension (PH) in
      myelopathy patients a standardized interview and chart review were carried out.
      Of 232 myelopathy patients with more than 2 years of paralysis seen during a 2
      year period, 30 had been treated for PH. All PH patients were paralysed at levels
      higher than thoracic 7. The highest risk patients were tetraplegic, motor
      complete, 24 of 73 (33%). The common symptoms of PH were those of reduced
      consciousness (100%), strength (75%), vision (56%) and breath (53%).
      Precipitating factors were hot weather (77%) bowel care (33%) and meals (30%).
      Symptoms worsened with the duration of paralysis in 12 patients. Chronic
      hyponatremia was found in 54% of the PH patients and 16% of those without, P <
      0.001. Of five PH-hyponatremic patients with urine sodium and osmolality
      determinations, five continued to retain water (> 150 mOsm/kg) while four failed
      to conserve salt (> 19 mmol Na/L). PH is common among myelopathy patients with
      higher levels of paralysis, symptoms are variable, and abnormal salt and water
      metabolism often coexist.

PMID- 9160456
TI  - Use of shoulder flexors to achieve isometric elbow extension in C6 tetraplegic
      patients during weight shift.
AB  - The anterior deltoid muscle has been found to be active during elbow extension in
      normal volunteers and in C6 tetraplegic patients lacking a functional triceps.
      Using surface electromyography (EMG) on normal volunteers and on patients with
      spinal cord injury (SCI) at the C6 motor level, we evaluated whether the anterior
      deltoid and biceps brachii muscles are active during closed chain elbow extension
      in a simulated weight shift position. Thirteen normal volunteers performed
      isometric contractions at 5 submaximal levels of force ranging from 4-25 kg. Six
      SCI patients performed isometric contractions at force levels of 20%, 40%, 60%,
      80% and 100% maximum voluntary contraction (MVC). Surface EMG over the right
      biceps, triceps, and anterior deltoid muscles was recorded for each participant
      and the root mean square (rms) electromyographic activity level for each muscle
      was determined at each level of force. Statistical analyses using repeated ANOVA
      with Tukey HSD post-hoc tests were performed for each level of force. The results
      indicated increasing rms activity of the triceps and anterior deltoid muscles
      with increasing force in normal volunteers to a significant degree (P < 0.05).
      SCI patients showed significant increasing activity of the anterior deltoid with
      increasing force, but showed minimal triceps rms activity. In both groups, the
      biceps showed minimal rms activity. SCI patients exhibited significantly greater
      rms activity of the anterior deltoid at low force compared with normal
      volunteers. The results suggest that the anterior deltoid aids in isometric elbow
      extension during a simulated weight shift maneuver.

PMID- 9160457
TI  - Predicting compliance with annual follow-up evaluations in persons with spinal
      cord injury.
AB  - A prospective study was performed to determine why some persons with spinal cord
      injury (SCI) fail to return for scheduled evaluations in order to identify
      predictive factors that could be used to target those at greatest risk for
      noncompliance and facilitate interventions to improve rates of return. Sixty-one
      noncompliant subjects and 102 persons compliant with regularly scheduled annual
      examinations were paid to come to the clinic for evaluation. Each participant
      completed a psychological questionnaire comprised of theoretical and
      socioeconomic variables. There was no difference between the two groups according
      to gender, race, level or completeness of injury, education, etiology of injury,
      responses to questions from the Health Locus of Control Scale, Health Beliefs
      Model, inconvenience or discomfort. For noncompliant versus compliant persons,
      cost (P = 0.0002), distance (P = 0.0047), transportation (P = 0.0330), belief
      that follow-up was not necessary (P < 0.0001), availability of good local doctor
      (P = 0.0001) and time (P = 0.0209) were identified as obstacles to returning for
      follow-up. These data indicate a need to improve the education for newly injured
      persons as well as those persons residing in the community on the importance of
      regular urological follow-up, to maintain close contact post-discharge and to
      assist in identifying community resources to facilitate either compliance with
      planned evaluations or the development of acceptable alternatives.

PMID- 9160458
TI  - Estimating social adjustment following spinal trauma--I: Who is more realistic-
      patient or spouse? A statistical justification.
AB  - Whilst assessment of functional independence has been accomplished, to a greater
      extent, following spinal trauma, assessing social adjustment remains an area
      requiring considerable further investigation. Providing premorbid estimation of
      adjustment is an area which presents a number of methodological difficulties both
      in the collection and interpretational of longitudinal data. Such analyses tend
      to allow overall estimates of adjustment to be made but which lack individual
      specificity. Analyses are presented of over 250 individuals, and their closest
      relative's assessment, of social adjustment to their spinal cord injury. Using a
      modification of an established scale for assessing social adjustment it has been
      possible to establish the statistical level of agreement and address the
      hypothesis of differential perception of the extent of adjustment problems by the
      injured person and their closest relative. The study allows for the conclusion
      that an injured person's perception of adjustment is at least as reliable as
      their closest relative, and that there is further evidence to support the
      essential accuracy of their estimations of premorbid and current levels of
      adjustment. Both issues are of clinical importance, particularly in relation to
      any medico-legal compensation aspects.

PMID- 9160459
TI  - A rational approach to long-term care: comparing the independent living model
      with agency-based care for persons with high spinal cord injuries.
AB  - Two groups of individuals with high level tetraplegia (C1-4) were compared with
      respect to the model of personal care assistance used. The study was undertaken
      to determine whether a finite population with severe disability had differences
      in health status, costs and perceived quality of life, relative to whether they
      used agencies for their care, or hired, trained and reimbursed care givers
      independently. A survey, which included demographics as well as portions of RAND
      36, LSI-A, PIP, PASI and CHART was used. Telephone interviews were held with 29
      individuals who received their care through an agency and 42 who managed care
      independently. Chi square, 't'-tests, and multiple regression analysis were used
      to control for potentially confounding group differences. The self-managed group
      demonstrated significantly better health outcomes, with fewer re-hospitalizations
      for preventable complications. They experienced better life satisfaction and
      significantly lower costs. Although those who used an independent model of care
      giving received significantly more hours of paid assistance, the average annual
      cost of care was significantly lower for each individual. In addition to reducing
      the financial burden on the individual and society, self-managed care seemed to
      diminish the emotional burden borne by these individuals.

PMID- 9160460
TI  - Extra pontine myelinolysis in a tetraplegic patient: case report.
AB  - Hyposmolar hyponatremia (serum sodium < 130 mmol/l) is a common phenomenon in the
      spinal cord injury (SCI) patient population and in most cases, it is of
      relatively little consequence. However, rapid correction or over correction of
      hyponatremia (a change in serum sodium > 25 mmol/l within 48 h) has been linked
      to Central Pontine Myelinolysis (CPM) and Extra Pontine Myelinolysis (EPM),
      usually along with other recognized predisposing factors. We report the first
      case of isolated Extra Pontine Myelinolysis in an SCI patient without any of the
      recognized predisposing factors, following correction of hyponatremia. The signs
      and symptoms of Extra Pontine Myelinolysis were not very remarkable in our
      patient because of prior spinal cord injury. The diagnosis was confirmed by the
      typical finding of myelinolysis in the basal ganglion region on MRI. Hyponatremia
      occurs frequently in the SCI patient population, thus placing them at increased
      risk for Extra Pontine Myelinolysis. Therefore, we emphasize the importance of
      watching for this entity during the management of hyponatremia in the SCI patient
      population and recommend the use of MRI scans to confirm the clinical diagnosis.

PMID- 9160461
TI  - Why does acute back pain become chronic?

PMID- 9160462
TI  - Effects of phospholipase A2 on lumbar nerve root structure and function.
AB  - STUDY DESIGN: To investigate the effects of phospholipase A2 on the
      neurophysiology and histology of rat lumbar spinal nerves and the corresponding
      behavioral changes. OBJECTIVES: To study possible mechanisms of sciatica. SUMMARY
      OF BACKGROUND DATA: The pathophysiology of sciatica is uncertain, although
      mechanical, chemical, and ischemic factors have been proposed. METHODS:
      Phospholipase A2 was injected into the rat L4-L5 epidural space, and the rats
      were observed for 3 or 21 days. Behavioral studies were conducted daily during
      the survival period. On the 3rd or 21st day, extracellular nerve recordings were
      made from dorsal roots, to determine discharge properties and mechanical
      sensitivity. The nerve roots were then sectioned for a light-microscopic
      examination. RESULTS: Motor weakness of hind limbs and altered sensation were
      observed. In the 3-day phospholipase A2 groups, squeezing the dorsal roots at the
      L4-L5 disc level (force = 0.8 g) evoked sustained ectopic discharge that lasted
      approximately 8 minutes. Squeezing the roots distal to the L4-L5 area did not
      result in sustained discharges. In sham, control, and 21-day phospholipase A2
      groups, squeezing the dorsal roots elicited only a transient firing that lasted
      approximately 0.1 second. Loss of myelin was seen in the nerve root cross
      sections in the 3-day group, and remyelination was observed in the 21-day group.
      No abnormality was found in the control groups. CONCLUSIONS: Based on these
      studies, it is hypothesized that phospholipase A2 causes demyelination that
      results in hypersensitive regions where ectopic discharge may be elicited by
      mechanical stimulation. These ectopic discharges may be a source of sciatica. We
      believe that, as long as these irritating factors are present, the hypersensitive
      nerve root nerve will continue to fire, and sciatic pain will persist.

PMID- 9160463
TI  - Toward a biochemical understanding of human intervertebral disc degeneration and
      herniation. Contributions of nitric oxide, interleukins, prostaglandin E2, and
      matrix metalloproteinases.
AB  - STUDY DESIGN: Normal and herniated human intervertebral disc specimens were
      cultured to study the effects of interleukin-1 beta on the production of nitric
      oxide, interleukin-6, prostaglandin E2, and matrix metalloproteinases. The
      effects of endogenously produced nitric oxide on the synthesis of other mediators
      also were studied. OBJECTIVES: To test the hypothesis that the cells of the
      intervertebral disc are metabolically active and are capable of responding to
      biochemical stimuli such as interleukin-1 beta in a manner that could engender
      degenerative changes. As part of this study, the authors also investigated some
      of the possible autocrine regulatory mechanisms that may operate during the
      biochemical responses of disc cells. SUMMARY OF BACKGROUND DATA: The authors
      previously showed, for the first time, that herniated cervical and lumbar disc
      specimens spontaneously produce increased amounts of nitric oxide, interleukin-6,
      prostaglandin E2, and certain matrix metalloproteinases. These results suggest
      that these biochemical agents are in some manner involved with degenerative
      processes in the intervertebral disc. This novel hypothesis merits further
      evaluation; the current communication reports the results of experiments designed
      to do so. METHODS: Fourteen normal, nondegenerated discs (control group) were
      obtained from seven patients undergoing anterior spinal surgery for trauma or
      lumbar scoliosis. Thirty-six herniated discs (18 lumbar and 18 cervical) were
      obtained from 30 patients undergoing surgery for persistent radiculopathy. The
      specimens were placed into tissue culture and incubated for 72 hours in the
      presence or absence of interleukin-1 beta and NG-monomethyl-L-arginine, and
      inhibitor of nitric oxide synthases, and the media were subsequently collected
      for biochemical analysis. Biochemical assays for matrix metalloproteinases,
      nitric oxide, interleukin-6, and prostaglandin E2 were performed. RESULTS:
      Normal, control disc specimens significantly increased their production of matrix
      metalloproteinases, nitric oxide, interleukin-6, and prostaglandin E2 in response
      to interleukin-1 beta. Herniated lumbar and cervical discs, which were
      spontaneously releasing increased levels of these biochemical agents, further
      increased their production of nitric oxide, interleukin-6, and prostaglandin E2
      in response to interleukin-1 beta. Blocking the biosynthesis of nitric oxide in
      interleukin-1 beta-stimulated disc cells provoked a large increase in the
      production of interleukin-6. CONCLUSIONS: Cells of the intervertebral discs are
      biologically responsive and increase their production of matrix
      metalloproteinases, nitric oxide, interleukin-6, and prostaglandin E2 when
      stimulated by interleukin-1 beta. The effect is more dramatic in normal,
      nondegenerated discs where spontaneous synthesis of these mediators is low.
      Nevertheless, cells of the herniated degenerated discs where spontaneous
      production was high were still capable of further increasing their synthesis of
      several of these biochemical agents in response to interleukin-1 beta.
      Endogenously produced nitric oxide appears to have a strong inhibitory effect on
      the production of interleukin-6, which suggests that autocrine mechanisms play an
      important role in the regulation of disc cell metabolism.

PMID- 9160464
TI  - The role of phospholipase A2 and nitric oxide in pain-related behavior produced
      by an allograft of intervertebral disc material to the sciatic nerve of the rat.
AB  - STUDY DESIGN: To elucidate the pathomechanisms of radicular pain secondary to
      lumbar disc herniation. OBJECTIVES: To evaluate whether intervertebral disc
      material applied to the sciatic nerve produces hyperalgesia, and if the
      hyperalgesia in influenced by inhibitors of phospholipase A2 and nitric oxide
      synthase. SUMMARY OF BACKGROUND DATA: Previously, the authors reported that
      application of nucleus pulposus and anulus fibrosus material to the lumbar
      epidural space produces different forms of hyperalgesia (mechanical versus
      thermal), with different and distinct histologic changes. Additional
      pharmacologic studies showed that phospholipase A2 and nitric oxide are involved
      in the mechanisms that produce the mechanical and thermal hyperalgesia,
      respectively, N omega-nitro-L-arginine methyl ester and mepacrine are relatively
      selective inhibitors of nitric oxide synthase and phospholipase A2, respectively.
      However, it is not known what the relation is between the hyperalgesia produced
      and the activation and involvement of phospholipase A2 and production of nitric
      oxide, or why the application of nucleus pulposus and nucleus pulposus with
      anulus fibrosus produces different types of hyperalgesia. METHODS: Experiments
      were performed in five groups of rats: The control group (no treatment), the sham
      group (exposure of the sciatic nerve only), the fat group (allografted fat on the
      sciatic nerve), the nucleus pulposus group (allografted nucleus pulposus) and the
      nucleus pulposus + anulus fibrosus group (allografted nucleus pulposus and anulus
      fibrosus). Withdrawal threshold and latency from mechanical pressure and a
      radiant heat to hind paws were measured preoperatively and postoperatively. After
      local sciatic nerve administration of N theta-nitro-L-arginine methyl ester or
      mepacrine into the operated site, sensitivities to noxious stimuli were
      reevaluated after treatment. RESULTS: Only rats in the nucleus pulposus group
      showed evidence of mechanical hyperalgesia. However, injection of N theta-nitro-L
      arginine methyl ester resulted in evidence of mechanical hyperalgesia in the
      nucleus pulposus + anulus fibrosus group. Mechanical hyperalgesia was produced in
      the nucleus pulposus group and after injection of N theta-nitro-L-arginine methyl
      ester in the nucleus pulposus+anulus fibrosus group, both of which returned to
      normal after mepacrine injection. There were no significant changes in
      sensitivity to thermal stimuli in any of the experimental groups. CONCLUSION: It
      appears that phospholipase A2 and nitric oxide play important but different roles
      in pathomechanisms of radicular pain in lumbar disc herniation.

PMID- 9160465
TI  - Histochemical demonstration of nitric oxide in herniated lumbar discs. A clinical
      and animal model study.
AB  - STUDY DESIGN: This study was designed to localize the cells that produce nitric
      oxide in a lumbar disc herniation by histochemical method, including in situ
      hybridization. OBJECTIVE: To clarify which cells in herniated lumbar discs
      produce nitric oxide. SUMMARY OF BACKGROUND DATA: It was reported that herniated
      lumbar intervertebral disc specimens in culture are capable of producing nitric
      oxide. METHODS: Surgical specimens from lumbar disc herniation were examined to
      determine nitric oxide synthase histologically using nicotinamide adenine
      dinucleotide phosphate diaphorase histochemistry. Allografts of intervertebral
      disc materials were placed on the epidural space at L6 level in the rat. Nitric
      oxide synthase was examined in the applied tissues using nicotinamide adenine
      dinucleotide phosphate diaphorase histochemistry and in situ hybridization
      histochemistry. RESULTS: Nicotinamide adenine dinucleotide phosphate diaphorase
      (nitric oxide synthase) positive cells were observed in 2 (40%) of 5 herniated
      disc materials in patients. The positive cells were mainly in granulation tissue
      around intervertebral disc materials. In animal models, nitric oxide synthase
      positive cells were observed in all specimens at 1 and 2 weeks postoperatively.
      Newly formed vessels and small round cells in granulation tissue around the
      grafted intervertebral disc showed positive reaction. In situ hybridization
      demonstrated the expression of inducible isoform of nitric oxide synthase
      messenger RNA (mRNA) identical to small round cells around the applied
      intervertebral disc. CONCLUSION: Nitric oxide in a lumbar disc herniation is
      mainly produced by cells in granulation tissue around the herniated
      intervertebral disc.

PMID- 9160466
TI  - Effects of hydrostatic pressure on matrix synthesis and matrix metalloproteinase
      production in the human lumbar intervertebral disc.
AB  - STUDY DESIGN: This study is a unique in vitro study on the effects of hydrostatic
      pressure on human intervertebral disc metabolism. OBJECTIVE: To investigate the
      effects of hydrostatic pressure on matrix synthesis and matrix metalloproteinase
      production in the human lumbar intervertebral disc. SUMMARY OF BACKGROUND DATA:
      Mechanical stress and hydrostatic pressures influence proteoglycan and protein
      synthesis rates in bovine articular cartilage and coccygeal discs. However, the
      mechanism of matrix synthesis regulation of the intervertebral disc under
      mechanical stress has not been elucidated. METHODS: Twenty-eight human lumbar
      intervertebral discs obtained from surgery and from cadavers at autopsy were
      used. Each tissue fraction was charged with medium in a plastic syringe and
      placed in a water-filled hydrostatic pressure-control vessel. The hydrostatic
      pressures applied were 1 (control), 3, and 30 atm (atm = atmospheres) for 2
      hours. The proteoglycan and protein synthesis rates were determined by
      radioisotope incorporation. The production of matrix metalloproteinase-3 and
      tissue inhibitor of metalloproteinases-1 were measured by a one-step enzyme
      immunoassay method using monoclonal antibodies. RESULTS: Three atm pressure
      stimulated proteoglycan synthesis rates in the nucleus pulposus and inner anulus
      (n = 14 in each tissue). Compared with the control group, 30 atm pressure
      significantly inhibited proteoglycan synthesis in the inner anulus (P = 0.011).
      In the nucleus pulposus, matrix metalloproteinase-3 production was stimulated at
      a pressure of 30 atm relative to 3 atm (P = 0.014, n = 16 in each tissue). The
      highest tissue inhibitor of metalloproteinases-1 production showed highest values
      at 3 atm pressure in the inner anulus (n = 16 in each tissue). CONCLUSION: The
      results suggest that hydrostatic pressure influences intervertebral disc cell
      metabolism. A physiologic level of hydrostatic pressure (3 atm) may act as an
      anabolic factor for stimulation of proteoglycan synthesis and tissue inhibitor of
      metalloproteinases-1 production. This may be essential for maintaining the matrix
      of the disc. If the pressure was 30 atm or more or 1 atm or less, a catabolic
      effect will be predominant, with reduction of proteoglycan synthesis rate and
      increase of matrix metalloproteinase-3 production. Abnormal hydrostatic pressure,
      therefore, may accelerate disc degeneration.

PMID- 9160467
TI  - Transfer of genes to chondrocytic cells of the lumbar spine. Proposal for a
      treatment strategy of spinal disorders by local gene therapy.
AB  - STUDY DESIGN: In the current study, chondrocytic cells from bovine intervertebral
      end plates were cultivated in vitro and modified genetically. OBJECTIVE: The
      authors intended to perform isolation and cultivation of cells from bovine end
      plates of the spine. They also intended to show, in principle, the feasibility of
      introducing exogenous genes into chondrocytic cells from bovine intervertebral
      end plates by way of retroviral vectors. SUMMARY OF BACKGROUND DATA: The
      involvement of cytokines in the destruction of articular cartilage is
      established. It appears possible that similar mechanisms may play a role in
      intervertebral disc degeneration and other spinal disorders. Conventional
      medication and surgery of intervertebral disc degeneration addresses neither the
      pathophysiology nor the chronicity of the disease. Therapeutic proteins carry
      great potential as locally produced drugs after transfer of their cognate genes
      to the sites of interest. METHODS: Vertebral end plate tissue was obtained from
      bovine os coccygis. Chondrocytic cells were isolated and cultured in vitro. The
      bacterial beta-galactosidase (LacZ) gene and, alternatively, the complementary
      DNA (DNA copy of the mRNA) of the human interleukin-1 receptor antagonist were
      introduced into the isolated cells by retrovirus mediated gene transfer. beta
      galactosidase activity was determined by staining, and interleukin-1 receptor
      antagonist protein was quantitated by enzyme-linked immunosorbent assay. RESULTS:
      Isolation and cultivation of chondrocytic end plate cells is possible. Native
      cells continue to grow in culture for more than 2 months. Transfer of the beta
      galactosidase gene to cultured cells resulted in approximately 1% beta
      galactosidase positive cells. Transfer of the interleukin-1 receptor antagonist
      complementary DNA resulted in the production of 24 ng/ml/10(6) cells interleukin
      1 receptor antagonist protein in 48 hours. CONCLUSIONS: The introduction of
      exogenous therapeutic genes into cells from the intervertebral end plate opens
      the possibility for a local gene-based treatment of intervertebral disc
      degeneration. This approach avoids some of the shortcomings of conventional drug-
      and surgery-based treatments and has the potential to be specific, effective, and
      appropriate to the chronicity of the disease.

PMID- 9160468
TI  - Chemonucleolysis with human stromelysin-1.
AB  - STUDY DESIGN: Immunohistologic analysis was performed on surgically removed
      samples of herniated nucleus pulposus to examine the expression of stromelysin-1.
      We performed in vitro and in vivo experiments to determine whether recombinant
      human (rh) stromelysin-1 is capable of degrading nucleus pulposus. OBJECTIVE: To
      analyze the production of stromelysin-1 in various types of herniated nucleus
      pulposus, and to examine the effects of this recombinant protein on nucleus
      pulposus tissues. SUMMARY OF BACKGROUND DATA: The authors previously demonstrated
      a progressive decrease in herniated nucleus pulposus size in some of the
      transligamentous and sequestration types of herniated nucleus pulposus using
      magnetic resonance imaging. An increased production of stromelysin-1, a cartilage
      proteoglycan degrading enzyme, in herniated nucleus pulposus was reported
      recently. The authors speculated that if stromelysin-1 is involved in the
      degradation of herniated nucleus pulposus, stromelysin-1 itself may be used as a
      chemonucleolytic agent. METHODS: Immunohistologic analysis using streptoavidin
      biotin method was performed on 20 herniated nucleus pulposus samples to
      investigate the expression of stromelysin-1. Five herniated nucleus pulposus
      samples were incubated in a tissue culture medium in the presence or absence of
      rh stromelysin-1. After 24 hours of incubation, their weight changes were
      measured, and the loss of proteoglycan was assessed by Safranin O staining. Rat
      nucleus pulposus tissues were obtained from coccygeal intervertebral discs, and
      autologous subcutaneous transplantation was performed. Rh stromelysin-1 was
      injected into the grafted materials, and the reduction in size was followed by
      two-dimensional measurements from the skin surface, using engineer's calipers.
      RESULTS: Immunohistologic analysis demonstrated the production of stromelysin-1
      in the granulation tissues of herniated nucleus pulposus. When stromelysin-1 was
      injected into the murine nucleus pulposus tissues, they reduced in size more
      rapidly than the control group. In addition, human herniated nucleus pulposus
      materials obtained at surgery showed significant weight loss when treated with
      stromelysin-1 in an organ culture system. Safranin O staining revealed extensive
      depletion of proteoglycan in these herniated nucleus pulposus samples.
      CONCLUSIONS: Stromelysin-1 is a possible key enzyme in herniated nucleus pulposus
      resorption, and stromelysin-1 may be a good candidate for use in
      chemonucleolysis. Administration of human stromelysin-1 may physiologically
      facilitate the resorption process of herniated nucleus pulposus, increase the
      healing rate and decrease complications after chemonucleolysis.

PMID- 9160469
TI  - Postlaminectomy adhesion of the cauda equina. Changes of postoperative vascular
      permeability of the equina in rats.
AB  - STUDY DESIGN: The authors evaluated the vascular permeability changes of the
      cauda equina after lumbar laminectomy in rats. OBJECTIVES: To clarify the early
      vascular responses in postlaminectomy adhesive arachnoiditis. SUMMARY OF
      BACKGROUND DATA: Laminectomy-induced cauda equina adhesion has been visualized by
      postoperative serial magnetic resonance imaging in humans. In laminectomized
      rats, fibrinous exudation was apparent among the adhered cauda equina. To date,
      there has been no report of substantial changes in vascular permeability in the
      cauda equina after lumbar laminectomy. METHODS: Wistar rats laminectomized from
      L5-L6 were used for four studies; 1) Evans blue albumin tracer study; 2)
      horseradish peroxidase tracer study; 3) lanthanum tracer study; and 4)
      fluoroscein isothiocyanate-dextran (molecular weights: 20K, 70K, and 150K) tracer
      study. Untreated rats were used as controls. RESULTS: 1) In the laminectomized
      (L5-L6) area, the cauda equina tended to conglomerate from 3 hours after surgery;
      this was relatively resolved by 6 weeks. Extravascular leakage of Evans blue
      albumin in the cauda equina appeared at 3 hours after surgery and reached a
      plateau at 24 hours; it mostly disappeared by 6 weeks. At 24 hours after surgery,
      the extent of Evans blue albumin extravasation was seen in one or more levels
      adjacent to the laminectomized area. Evans blue albumin leakage and cauda equina
      adhesion started to appear in nearly a same phase after laminectomy, followed by
      a plateau of vascular permeability facilitating complete cauda equina adhesion by
      24 hours after surgery. The restoration of Evans blue albumin leakage was noted 1
      week after surgery, and tended to precede recovery of the cauda equina adhesion;
      2) in the laminectomy group, Horseradish peroxidase penetrated from the lumen to
      the extracellular space beyond the basal laminae of the endothelial cells.
      Numerous horseradish peroxidase-labeled vesicles in the endothelial cells were
      found; 3) There was a significant increase in lanthanum distribution in the
      endothelial cytoplasm at the laminectomized levels. Lanthanum filled the
      interendothelial clefts beyond the tight junction, but did not penetrate through
      the perivascular basal laminae; 4) Fluoroscein isothiocyanate-dextran (20K, 70K,
      150K) permeability increased in the laminectomy group, but there was no
      difference in extravasation of fluoroscein isothiocyanate-dextran, irrespective
      of the molecular weight. CONCLUSION: Laminectomy consistently induced an increase
      in vascular permeability in the cauda equina, an increase of vesicular transport
      in the endothelial cell, and opening of the tight junction early after
      laminectomy, suggesting breakdown of the blood nerve barrier in the cauda equina.
      The accelerated permeability may enhance cauda equina adhesion.

PMID- 9160470
TI  - A prospective study of centralization of lumbar and referred pain. A predictor of
      symptomatic discs and anular competence.
AB  - STUDY DESIGN: The presence or absence of rapidly centralizing, peripheralizing,
      or abolishing low back and radiating pain, as identified during a McKenzie
      mechanical lumbar assessment of patients with chronic lumbar pain, was compared
      prospectively with discographic pain provocation and anular competency.
      OBJECTIVES: To evaluate any relation between the responses of centralization and
      peripheralization with discographic findings. SUMMARY OF BACKGROUND DATA:
      Centralization of referred pain has been reported as a very common occurrence
      during McKenzie assessment and treatment. Patients whose pain centralizes have
      been shown to achieve superior treatment outcomes. A dynamic internal disc model
      has been hypothesized as an underlying mechanism for centralization that has not
      been studied previously. METHODS: Patients with chronically disabling low back
      pain who were referred for discography underwent preliminary blinded McKenzie
      clinical assessment and were categorized into three groups by their pain
      response. Patterns, or lack thereof, of pain response were then compared with
      blinded discographic pain provocation and anular findings. RESULTS: During the
      McKenzie assessment, the referred pain of 50% centralized with 74% having
      positive discograms, of which 91% had an intact anulus. The pain of 25%
      peripheralized only (would not centralize); 69% of these had positive discograms,
      but only 54% had an intact anulus. The distal pain of 25% did not respond at all,
      and only 12.5% of these had positive discograms. CONCLUSION: The McKenzie
      assessment process reliably differentiated discogenic from nondiscogenic pain (P
      < 0.001) as well as competent from an incompetent anulus (P < 0.042) in
      symptomatic discs and was superior to magnetic resonance imaging in
      distinguishing painful from nonpainful discs.

PMID- 9160471
TI  - Lumbar laminectomy alone or with instrumented or noninstrumented arthrodesis in
      degenerative lumbar spinal stenosis. Patient selection, costs, and surgical
      outcomes.
AB  - DESIGN: A prospective, multicenter observational study. OBJECTIVES: 1) Identify
      correlates of the decision to perform arthrodesis in patients undergoing
      laminectomy for lumbar spinal stenosis. 2) Compare symptoms, walking capacity,
      and satisfaction 6 and 24 months after laminectomy alone and laminectomy with
      noninstrumented and with instrumented arthrodesis. BACKGROUND DATA: Few
      prospective studies have compared outcomes of laminectomy alone or laminectomy
      with noninstrumented or with instrumented arthrodesis in patients with
      degenerative lumbar spinal stenosis. There is uncertainty regarding the optimal
      use of arthrodesis and instrumentation. METHODS: Two hundred seventy--two
      patients undergoing--surgery for degenerative lumbar stenosis by eight surgeons
      at four centers were included in the study cohort. Of these, 37 had
      noninstrumented and 41 had instrumented arthrodesis. Logistic regression
      identified factors associated with arthrodesis. The principal outcomes-health
      status, walking capacity, back and leg pain, and satisfaction with surgery-were
      assessed 6 and 24 months postoperatively with univariate and multivariate
      techniques. Outcomes also were assessed in a restricted cohort of patients with
      at least 5 mm spondylolisthesis and/or 15 degrees scoliosis. Hospital costs were
      obtained from a computerized hospital cost accounting system. RESULTS: The major
      predictor of the decision to perform arthrodesis was the individual surgeon (P =
      0.0001). Noninstrumented arthrodesis was associated with superior relief of low
      back pain at 6 months (P = 0.004) and 24 months (P = 0.01). This difference
      persisted in multivariate analyses, with borderline statistical significance.
      There were no significant differences in the other outcomes across treatment
      groups. Mean hospital costs of laminectomy alone and noninstrumented and
      instrumented arthrodesis were $12,615, $18,495, and $25,914, respectively (P =
      0.0001). CONCLUSION: Findings were limited by the small number of participating
      surgeons, modest sample size that produced P values of borderline significance,
      and nonrandomized design. With these caveats in mind, the authors conclude: (1)
      The individual surgeon was a more important correlate of the decision to perform
      arthrodesis than clinical variables such as spondylolisthesis. (2)
      Noninstrumented arthrodesis resulted in superior relief of back pain after 6 and
      24 months. (3) Instrumented arthrodesis was the most costly option. These results
      highlight the need for randomized controlled trials and cost effectiveness
      analyses of lumbar arthrodesis and instrumentation in patients with degenerative
      lumbar spinal stenosis.

PMID- 9160472
TI  - The prevalence of low back pain among children and adolescents. A nationwide,
      cohort-based questionnaire survey in Finland.
AB  - STUDY DESIGN: A nationwide, cohort-based cross-sectional questionnaire survey as
      a part of a population study. OBJECTIVES: To evaluate the prevalence of low back
      pain among Finnish children and adolescents. SUMMARY OF BACKGROUND DATA: Low back
      pain is common already in adolescence, but the results concerning sex differences
      and peak age of the prevalence have been partly controversial. Also, previous
      studies have been limited to smaller geographic areas. METHODS: The subjects were
      594 girls and 577 boys, a total of 1171 children and adolescents. They were
      pupils of 45 different public schools. Various areas of Finland were included in
      the sampling process to represent different parts of the country and different
      living conditions. The subjects completed a validated questionnaire by themselves
      or with the help of a parent or guardian. The questionnaire was checked by a
      supervisor when entering the field study. The questionnaire included items that
      investigated the subjects' past and current low back pain. Low back pain was
      classified on the basis of timing, duration, and location. Subjects reporting
      pain in the low back area that interfered with school work or leisure activities
      during the previous 12 months were defined as having low back pain. RESULTS: The
      prevalence of back pain was low (1%) among the 7-year-old and 10-year-old (6%)
      schoolchildren, but increased with age, being 18% both among 14- and 16-year-old
      adolescents. No gender difference was found. Recurrent or chronic pain was
      reported by 26% of the boys and 33% of the girls who reported low back pain, and
      the proportion of recurrent and chronic pains of all low back pain incidents
      increased with age. CONCLUSIONS: Low back pain is a relatively common complaint
      at adolescence. In addition, a significant part of the pains are recurrent or
      chronic already with 14-year-old adolescents.

PMID- 9160473
TI  - Psychosocial factors in the workplace--do they predict new episodes of low back
      pain? Evidence from the South Manchester Back Pain Study.
AB  - STUDY DESIGN: A prospective, population-based cohort study of working adults.
      OBJECTIVES: To determine whether work-related psychosocial factors and social
      status predict the occurrence of new episodes of low back pain and influence
      consultation behavior. SUMMARY AND BACKGROUND DATA: Dissatisfaction with work and
      social status has been associated with low back pain in several studies; few of
      these studies have been prospective or population based. METHODS: An initial
      postal survey was returned by 4,501 (59%) adults (18-75 years old) registered
      with two primary care practices. From this, a cohort of 1,412 people currently in
      employment and free of low back pain was identified, and baseline information on
      work-related psychosocial factors and psychologic distress was obtained. Social
      class was derived from current occupation using a standardized classification.
      New episodes of low back pain occurring in the next 12 months were identified by
      continuous monitoring of primary care consulters and by mailing a second
      questionnaire a year later to identify occurrences of low back pain for which no
      consultation was sought. RESULTS: The baseline cross-sectional survey showed
      modest but significant associations between low back pain and perceived
      inadequacy of income (risk ratio 1.3), dissatisfaction with work (risk ratio 1.4)
      and social class IV/V (risk ratio 1.2). In the follow-up year, the risk of
      reporting low back pain for which no consultation was sought doubled in those
      dissatisfied with their work. Both perceived inadequacy of income (odds ratio
      3.6) and social class IV/V (odds ratio 4.8) were strongly associated with
      consulting with a new episode of low back pain during the follow-up year, an
      association more marked in women. The associations with work dissatisfaction and
      perceived adequacy of income were not explained by general psychologic distress
      or social status. CONCLUSION: People dissatisfied with work are more likely to
      report low back pain for which they do not consult a physician, whereas lower
      social status and perceived inadequacy of income are independent risks for
      working people to seek consultation because of low back pain.

PMID- 9160475
TI  - Growth changes of solidly fused kyphotic bloc after surgery for tuberculosis.
      Comparison of four procedures.
AB  - STUDY DESIGN: A study to analyze the changes of the spinal deformity during the
      growth period, with regard to different operations for spinal tuberculosis in
      children. OBJECTIVES: To quantify the changes in the kyphotic angle and the
      growth ratio of the fusion bloc during spinal growth for different fusion
      techniques. SUMMARY OF BACKGROUND DATA: Most of the publications dealing with
      spinal tuberculosis in children focused on the clinical outcome with regard to
      different conservative and operative treatments. There is little reliable
      information concerning the growth of the solidly fused kyphotic bone bloc and its
      influence on the changes of the kyphotic deformity after different operative
      procedures. METHODS: The study included 117 children operated on for spinal
      tuberculosis at the age of 2-6 years at the Ruttonjee Sanatorium in Hong Kong
      during the 1950s and 1960s. Lateral radiographs obtained postoperatively and 5
      and 10 years after the operation were analyzed for the growth changes of the
      solidly fused bone bloc. These results were compared with the different operation
      techniques (e.g., anterior fusion, posterior fusion, combined anterior and
      posterior fusion, and anterior debridement without fusion). RESULTS: The patients
      treated by anterior fusion showed the worst results with respect to the kyphotic
      angle. This was especially true when the lesion was located in the thoracic spine
      and several segments were involved. Regarding the growth ratio of the fusion
      bloc, only the combined fusion and the anterior debridement guaranteed an equal
      growth of the anterior and posterior height. CONCLUSIONS: Radical anterior
      surgery for spinal tuberculosis destroys the anterior growth and limits the
      capacity for spinal remodeling. Therefore, it should be avoided, if it is not
      absolutely necessary, for the healing of the infection or the primary correction
      of the tuberculous deformity.

PMID- 9160474
TI  - Employment and physical work activities as predictors of future low back pain.
AB  - STUDY DESIGN: A population-based longitudinal study conducted in northwest
      England for a 12-month period involving adults aged 18-75 years. OBJECTIVES: To
      determine physical factors related to employment that predict a new episode of
      low back pain. SUMMARY OF BACKGROUND DATA: Most epidemiologic studies that have
      examined the relation between occupation and back pain have been cross-sectional
      or retrospective in design. Because workers who have experienced low back pain
      may have changed jobs or work activities, it is important to use longitudinal
      studies that define "exposures" before the onset of symptoms. METHODS: From
      adults registered with two general practices in northwest England, 1412 people
      who were currently in employment and free of low back pain were identified. A
      lifetime occupational history was recorded for all participants, with details of
      activities performed in each occupation. Data on consultations for low back pain
      during the follow-up year were collected through computerized medical records,
      whereas those who had not consulted with low back pain were sent another
      questionnaire at the end of the 1-year follow-up. RESULTS: An increased risk of a
      new episode of low back pain was found in those whose jobs involved
      lifting/pulling/pushing objects of at least 25 lbs, or whose jobs involved
      prolonged periods of standing or walking. Risks were, in general, greater in
      women, for a first ever episode of back pain and for back pain that led to a
      general practice consultation. No clear relation between years of exposure to
      such factors and magnitude of risk was evident. CONCLUSIONS: Occupational
      activities, particularly in women, such as working with heavy weights or lengthy
      periods of standing or walking, were associated with the occurrence of low back
      pain. Short-term influences may be more important in the occurrence of new
      episodes rather than cumulative lifetime exposure, and emphasize that such
      morbidity may be avoidable.

PMID- 9160476
TI  - Entrapment neuropathy of the medial superior cluneal nerve. Nineteen cases
      surgically treated, with a minimum of 2 years' follow-up.
AB  - STUDY DESIGN: In this study, the authors analyzed the results of the release of
      the medial superior cluneal nerve in a prospective series of 19 patients with
      suspected entrapment. OBJECTIVES: To ascertain, in selected patients with low
      back pain, medial superior cluneal nerve entrapment compromise at the posterior
      iliac crest crossing site, and to evaluate the results of nerve release. SUMMARY
      OF BACKGROUND DATA: A cadaveric study had shown that the medial superior cluneal
      nerve may be compressed at its transit site through an osseofibrous orifice at
      the posterior iliac crest. METHODS: Nineteen patients suffering from unilateral
      low back pain projecting in the territory of the medial superior cluneal nerve,
      with a trigger point at the posterior iliac crest and with a positive block test
      at this level, underwent surgery. RESULTS: Results were excellent in 13 cases (7
      of which had suffered from severe compression), and unsatisfactory in 6 cases
      (including 4 cases in whom no compression could be demonstrated). CONCLUSION:
      Entrapment neuropathy of the medial superior cluneal nerve is a rare and easily
      treatable cause of unilateral low back pain.

PMID- 9160477
TI  - In vitro simulation. Early results of stereotaxy for pedicle screw placement.
AB  - STUDY DESIGN: Frameless stereotaxy with doppler ultrasound and three dimensional
      computer model registration is assessed in vitro for pedicle screw placement.
      OBJECTIVE: To identify feasibility of pedicle screw navigation and placement
      using this technology. SUMMARY OF BACKGROUND DATA: Inaccurate pedicle screw
      placement can lead to neurovascular injury or suboptimal fixation. Present
      techniques in pedicle screw placement involve only confirmation of hole
      orientation. METHOD: Forty-four pedicle screws were placed in lumbosacral models
      and cadaver specimens. Accuracy was assessed with a computed tomography scan and
      vertebral cross sectioning. RESULTS: All screws were intrapedicular. Accuracy of
      anterior cortical fixation was 1.5 mm, with a range of 2.5 mm. CONCLUSION: In
      vitro frameless stereotaxy is accurate for pedicle screw placement. This
      technology adds a component of navigation to pedicle screw placement.

PMID- 9160478
TI  - Exercise and relaxation in health promotion.
AB  - The growing size of world cities and ever more competitive working conditions are
      thought to cause subjective stress, anxiety and depression, with a resulting
      decrease in the quality of life, sleep disturbances, drug and alcohol abuse and
      poor productivity. Acute stress may suppress immune function, leading to an
      increased incidence of infections, and chronic stress may predispose to a number
      of ailments, including digestive disturbances, hypertension, ischaemic heart
      disease and neoplasia; jointly, these factors cause a substantial shortening of
      life expectancy. The control of stress thus makes an important contribution to
      health. Stress levels can be reduced by anxiolytic drugs, or by a variety of
      psychological techniques; however, an appropriate programme of physical activity
      may be the preferred option, since exercise has many positive effects on health
      that are unrelated to stress. If exercise is to be effective in inducing
      relaxation, it must be noncompetitive, moderate in intensity, and pursued in
      pleasant surroundings.

PMID- 9160479
TI  - Exercise and gall bladder function.
AB  - Epidemiological research has demonstrated protective effects of varying strength
      from physical activity against the risk for several chronic diseases such as
      coronary heart disease, hypertension, non-insulin-dependent diabetes mellitus and
      osteoporosis. Epidemiological studies have been supported by experimental
      research showing that exercise training improves coronary heart disease risk
      factors and other health-related factors. In contrast, the association between
      physical activity, exercise and gall stone disease has not yet been firmly
      established. This paper presents the theoretical role of aerobic exercise: (i) in
      the primary prevention of gall stone disease; and (ii) as a potential prokinetic
      agent in high risk gall stone disease groups. Primary risk factors in the
      pathogenesis of gall stone formation include cholesterol supersaturation in the
      solutes that precipitate from bile, hypernucleation (measured as "crystal
      appearance time') and finally hypomotility of the gall bladder which allows bile
      stasis and crystal formation. While the results of epidemiological studies
      suggest that physical activity may be inversely associated with gall stone
      disease, the mechanisms by which exercise may influence gall stone disease
      pathogeneses are poorly understood. In this paper the association between
      physical activity and exercise to gall bladder function and gall stone disease
      will be examined. Recommendations for future research and the implications for
      the primary prevention of gall stone disease will also be discussed.

PMID- 9160480
TI  - Aetiology and occurrence of diving injuries. A review of diving safety.
AB  - This paper examines multifaceted aspects of diving entries into water which are
      the cause of many critical injuries (costed at $A150 million) and therefore have
      important safety ramifications. Wedge and compression fractures are most commonly
      found in the cervical area of the spine with off-centre impacts with the pool or
      sea bottom. Diving-related injuries range from 2.3 in a South African study to
      21% of spinal cord injuries in Poland. Alcohol and diving do not mix because of
      diminished awareness and information processing. Children aged under 13 years
      suffer fewer cervical injuries (1 to 4%), but complication rates are relatively
      high for this group. Sports trauma (diving-related in particular) is one of the
      more prevalent causes of spinal cord injury in children aged 6 to 15 years. The
      highest incidence occurs among those aged 10 to 14, followed by the group aged 5
      to 9 years. This contradicts the common perception that 15-to 19-year-olds
      comprise the highest risk group. Boys are more frequently injured, and swimming
      pools are more common as an injury location then is the case with adults. The
      role played by water depth has been conclusively ascertained; technique, and
      therefore education, appear to be more important considerations in injury
      prevention. Although 89% of injuries occur in water < 1.52m, injuries are rare in
      water of 0.46 to 0.61m. Care with pool design to avoid sudden depth changes and
      the resultant "spinal wall' is necessary. Minimum depth values for diving vary
      from 1 to 1.52 m. Velocities and angles of entry are considered to ascertain the
      body's decelerative capacity upon entry. The scoop, racing start dive has been
      shown to require at least 1.22 m of water even when practised by trained divers;
      the risks involved must therefore be weighed against the fact that it may be no
      faster than more conventional dives. While it may be safe to perform kneeling and
      crouching dives into shallowers water, standing dives by untrained divers require
      a greater margin of error. Lack of education is an issue which needs to be
      addressed and this paper makes recommendations for safety practices such as
      steering up to the surface, head protection with the arms and only diving when
      absolutely necessary.

PMID- 9160481
TI  - A physiological review of American football.
AB  - American football has been one of the most popular sports in North America within
      the past century and has recently received support and increased participation
      from European nations. Two of the biggest concerns regarding participation in
      American football are the high incidence of injury and the physical demand for
      preparation. A basic understanding of the physiological systems utilised in the
      sport of football is necessary in order to develop optimal training programmes
      geared specifically for preparation as well as the requirements of individual
      field positions. Previously, it has been assumed that football relies primarily
      on an anaerobic source of energy for adenosine triphosphate (ATP) resynthesis
      with approximately 90% coming from the phosphocreatine (PCr) energy system. In
      lieu of research conducted specifically with football players, it appears that
      the energy contribution from the anaerobic glycolytic pathway in this sport has
      been underestimated. The elevated blood lactate levels observed in football
      players following game participation cast doubt on this hypothesis. Identifying
      position specific characteristics may also enhance the development of training
      programmes based on the requirements of the different positions. It appears that
      offensive and defensive linemen are generally larger, have higher levels of
      percent body fat and have greater absolute strength scores than all other
      positions. Offensive backs, defensive backs and wide receivers tend to display
      the lowest percentages of body fat, lower absolute strength scores, fastest times
      over 5, 10, 40 and 300m and the highest relative VO2max values. Linebackers
      appeared to represent a transition group mid way between the backs and linemen
      for size, body composition, strength, speed and endurance as well as positional
      duties. Findings within the literature suggest that a lack of cardiovascular
      development of university and professional football players may prove to be a
      hindrance to performance with specific regards to thermal regulation. Additional
      aerobic conditioning as well as the reduction of percent body fat would not only
      enhance performance, but might play a key role in preventing injuries and
      allowing a smoother transition into life after football.

PMID- 9160482
TI  - Rock climbing injuries.
AB  - Three-quarters of elite and recreational sport climbers will suffer upper
      extremity injuries. Approximately 60% of these injuries will involve the hand and
      wrist, the other 40% will be equally divided between the elbow and the shoulder.
      Most injuries will be tendonopathies secondary to strains, microtrauma or flexor
      retinacular irritation. However, up to 30% of these injuries in up to 50% of
      elite climbers will involve the proximal interphalangeal (PIP) region. These
      injuries are more serious and consist of varying degrees of flexor digitorum
      sublimis insertional strains, digital fibro-osseous sheath ruptures and PIP joint
      collateral ligament strains. Early changes in climbing schedules, stretching and
      exercise habits, and protective digital taping are necessary to protect and
      rehabilitate these athletes.

PMID- 9160483
TI  - An overview of statistical methods for multiple failure time data in clinical
      trials.
AB  - In a long term clinical trial to evaluate a new treatment, quite often each study
      subject may experience a number of 'failures' that correspond to repeated
      occurrences of the same type of event or events of entirely different natures
      during his/her follow-up period. To obtain efficient inference procedures for the
      therapeutic effect over time, it is desirable to utilize those multiple event
      times in the analysis. In this article, we review some useful procedures for
      analysing different kinds of multivariate failure time data. Specifically, we
      discuss the two-sample problems and the general regression problems with various
      survival models. We also give some recommendations of appropriate procedures for
      each type of multiple event data structure for practical usage.

PMID- 9160484
TI  - Regression models for recurrent event data: parametric random effects models with
      measurement error.
AB  - Statistical methodology is presented for the statistical analysis of non-linear
      measurement error models. Our approach is to provide adjustments for the usual
      maximum likelihood estimators, their standard errors and associated significance
      tests in order to account for the presence of measurement error in some of the
      covariates. We illustrate the technique with a mixed effects Poisson regression
      model for recurrent event data applied to a randomized clinical trial for the
      prevention of skin tumours.

PMID- 9160485
TI  - Power considerations for clinical trials using multivariate time-to-event data.
AB  - Many clinical trials involve the collection of data on the times to occurrence of
      different types of events, such as different fungal infections in AIDS research,
      or of recurrences of the same type, such as successive fits in epilepsy research.
      The multivariate proportional hazards model allows for analysis of this data and
      software for doing this is now widely available. In this paper, the approximate
      power of a clinical trial that aims to use such data for comparing two treatments
      is derived. Special attention is given to the bivariate case, both to show that
      the approximation works well and to illustrate how various design parameters
      affect the power of a trial. As with any multivariate data in clinical trials,
      there are many conceptual issues that should be considered during trial design;
      the paper closes with a discussion of some of these.

PMID- 9160486
TI  - Bivariate modelling of clustered continuous and ordered categorical outcomes.
AB  - Simultaneous observation of continuous and ordered categorical outcomes for each
      subject is common in biomedical research but multivariate analysis of the data is
      complicated by the multiple data types. Here we construct a model for the joint
      distribution of bivariate continuous and ordinal outcomes by applying the concept
      of latent variables to a multivariate normal distribution. The approach is then
      extended to allow for clustering of the bivariate outcomes. The model can be
      parameterized in a way that allows writing the joint distribution as a product of
      a standard random effects model for the continuous variable and a correlated
      cumulative probit model for the ordinal outcome. This factorization suggests
      convenient parameter estimation using estimating equations. Foetal weight and
      malformation data from a developmental toxicity experiment illustrate the
      results.

PMID- 9160487
TI  - Non-parametric inference for cumulative incidence functions in competing risks
      studies.
AB  - In the competing risks problem, a useful quantity is the cumulative incidence
      function, which is the probability of occurrence by time t for a particular type
      of failure in the presence of other risks. The estimator of this function as
      given by Kalbfleisch and Prentice is consistent, and, properly normalized,
      converges weakly to a zero-mean Gaussian process with a covariance function for
      which a consistent estimator is provided. A resampling technique is developed to
      approximate the distribution of this process, which enables one to construct
      confidence bands for the cumulative incidence curve over the entire time span of
      interest and to perform Kolmogorov-Smirnov type tests for comparing two such
      curves. An AIDS example is provided.

PMID- 9160488
TI  - Marginal analysis of recurrent events and a terminating event.
AB  - Chronic medical conditions are often manifested by the incidence of recurrent
      adverse clinical events. In clinical trials designed to investigate therapeutic
      interventions for such conditions it is natural to make treatment comparisons on
      the basis of event occurrence. However, when there is a more serious, possibly
      related, event that terminates the occurrence of the recurrent events, the
      problem of dependent censoring arises. Here, we consider robust modelling
      strategies for expressing covariate effects on the recurrent event process that
      address the possible dependence between the recurrent and terminal events. The
      various methods differ in the way the dependence is addressed, and hence in the
      interpretation of covariate effects. The methods are applied to a data set from a
      kidney transplant study and simulated data chosen for illustrative purposes.

PMID- 9160489
TI  - Use of the Wei-Lin-Weissfeld method for the analysis of a recurring and a
      terminating event.
AB  - We consider application of the Wei-Lin-Weissfeld (WLW) method for multiple
      failure time data when analysing a disease process consisting of a recurring
      outcome, such as clinical progression, and a terminating outcome, such as death.
      In order to adapt WLW for this situation, 'events' must be specified that define
      multiple failure times and whether these are censored. Various choices of events
      are possible, and each corresponds to inferences about a different aspect of the
      underlying disease process. Definitions which regard the terminating outcome as a
      censor of the recurring outcome focus on specific cause-specific hazard
      functions, while event definitions which make no distinction between a recurring
      and terminating outcome focus on hazard functions of the induced failure times.
      Some event definitions require strong statistical assumptions to yield valid
      inferences and are not recommended. The application of WLW for
      recurring/terminating processes is illustrated with the results of two recently
      conducted clinical trials in persons with HIV.

PMID- 9160490
TI  - Multiple statistics for multiple events, with application to repeated infections
      in the growth factor studies.
AB  - Clinical studies that involve the recording of two or more distinct and well
      defined events on each subject give rise to multiple event data. Treatment
      comparisons are usually reported in univariate analyses of time to first event or
      number of events observed. However, this approach may not uncover the 'full
      story' of the treatment effect; moreover, it may be inefficient because it does
      not make full use of the available data. There are a number of published
      statistical methods for analysing multiple event data. Using data from a real
      life example, this paper compares the results obtained using the 'older ad hoc'
      methods with those based on the more recent methods that utilize the multiplicity
      of the data.

PMID- 9160491
TI  - Analysis of multiple failure time data from an AIDS clinical trial.
AB  - The primary endpoint of AIDS prophylaxis trials is the occurrence of
      opportunistic infections. While the treatments are not expected to have an effect
      on the underlying HIV disease, an effect of treatments on mortality cannot be
      ruled out. Therefore, the primary analysis of these trials must be based on a
      combined endpoint of infection and survival times. There are several methods
      available for analysis of multiple failure time data. However, there is no
      standard method for combining mortality and other failures in these analyses.
      This paper explores the analysis of multiple infections in the context of a study
      in which treatments may have an effect on mortality. The methods are applied to
      an AIDS clinical trial of prophylaxis for fungal infections.

PMID- 9160492
TI  - A comparison of goodness-of-fit tests for the logistic regression model.
AB  - Recent work has shown that there may be disadvantages in the use of the chi
      square-like goodness-of-fit tests for the logistic regression model proposed by
      Hosmer and Lemeshow that use fixed groups of the estimated probabilities. A
      particular concern with these grouping strategies based on estimated
      probabilities, fitted values, is that groups may contain subjects with widely
      different values of the covariates. It is possible to demonstrate situations
      where one set of fixed groups shows the model fits while the test rejects fit
      using a different set of fixed groups. We compare the performance by simulation
      of these tests to tests based on smoothed residuals proposed by le Cessie and Van
      Houwelingen and Royston, a score test for an extended logistic regression model
      proposed by Stukel, the Pearson chi-square and the unweighted residual sum-of
      squares. These simulations demonstrate that all but one of Royston's tests have
      the correct size. An examination of the performance of the tests when the correct
      model has a quadratic term but a model containing only the linear term has been
      fit shows that the Pearson chi-square, the unweighted sum-of-squares, the Hosmer
      Lemeshow decile of risk, the smoothed residual sum-of-squares and Stukel's score
      test, have power exceeding 50 per cent to detect moderate departures from
      linearity when the sample size is 100 and have power over 90 per cent for these
      same alternatives for samples of size 500. All tests had no power when the
      correct model had an interaction between a dichotomous and continuous covariate
      but only the continuous covariate model was fit. Power to detect an incorrectly
      specified link was poor for samples of size 100. For samples of size 500 Stukel's
      score test had the best power but it only exceeded 50 per cent to detect an
      asymmetric link function. The power of the unweighted sum-of-squares test to
      detect an incorrectly specified link function was slightly less than Stukel's
      score test. We illustrate the tests within the context of a model for factors
      associated with low birth weight.

PMID- 9160493
TI  - Variation of sensitivity, specificity, likelihood ratios and predictive values
      with disease prevalence.
AB  - The sensitivity, specificity and likelihood ratios of binary diagnostic tests are
      often thought of as being independent of disease prevalence. Empirical studies,
      however, have frequently revealed substantial variation of these measures for the
      same diagnostic test in different populations. One reason for this discrepancy is
      related to the fact that only few diagnostic tests are inherently dichotomous.
      The majority of tests are based on categorization of individuals according to one
      or several underlying continuous traits. For these tests, the magnitude of
      diagnostic misclassification depends not only on the magnitude of the measurement
      or perception error of the underlying trait(s), but also on the distribution of
      the underlying trait(s) in the population relative to the diagnostic cutpoint.
      Since this distribution also determines prevalence of the disease in the
      population, diagnostic misclassification and disease prevalence are related for
      this type of test. We assess the variation of various measures of validity of
      diagnostic tests with disease prevalence for simple models of the distribution of
      the underlying trait(s) and the measurement or perception error. We illustrate
      that variation with disease prevalence is typically strong for sensitivity and
      specificity, and even more so for the likelihood ratios. Although positive and
      negative predictive values also strongly vary with disease prevalence, this
      variation is usually less pronounced than one would expect if sensitivity and
      specificity were independent of disease prevalence.

PMID- 9160494
TI  - Improved odds ratio estimation by post hoc stratification of case-control data.
AB  - We propose a logistic regression analysis of unmatched or frequency matched case
      control studies with conditional maximum likelihood estimation through post hoc
      stratification. In this model fewer parameters have to be estimated. With a
      simulation study we show that parameter estimates have smaller variance and are
      less biased. Also, the residual confounding effect was quantified. A more refined
      post hoc stratification reduces computing time, but to the cost of a larger bias
      and a loss in efficiency. The model was also applied to data of unmatched case
      control studies on laryngeal cancer, oesophageal cancer and lung cancer.

PMID- 9160495
TI  - Estimating a relative risk across sparse case-control and follow-up studies: a
      method for meta-analysis.
AB  - Meta-analysis is the quantitative technique of combining results from different
      studies. There is a variety of procedures available for combining effect measures
      across epidemiologic studies. None of these methods provides an overall effect
      estimate when the data are sparse within studies and come from different study
      designs. In this paper we discuss the statistical relations between case-control
      studies and two types of follow-up studies. We use these relations to develop an
      exact methodology for combining results across study designs. We also use these
      relations to derive Mantel-Haenszel type formulae for summarizing results across
      studies. We illustrate these techniques with data pertaining to breast implants
      and connective tissue disease.

PMID- 9160497
TI  - Statistical methods for two-sequence three-period cross-over designs with
      incomplete data.
AB  - In clinical trials, and in bioavailability and bioequivalence studies, one often
      encounters replicate cross-over designs such as a two-sequence three-period cross
      over design to assess treatment and carry-over effects of two formulations of a
      drug product. Because of the potential dropout (or for some administrative
      reason), however, the observed data set from a replicate cross-over design is
      incomplete or unbalanced so that standard statistical methods for a cross-over
      design may not apply directly. For inference on the treatment and carry-over
      effects, we propose a method based on differences of the observations that
      eliminates the random subject effects and thus does not require any
      distributional condition on the random subject effects. When no datum is missing,
      this method provides the same results as the ordinary least squares method. When
      there are missing data, the proposed method still provides exact confidence
      intervals for the treatment and carry-over effects, as long as the dropout is
      independent of the measurement errors. We provide an example for illustration.

PMID- 9160496
TI  - Adjusting for non-compliance and contamination in randomized clinical trials.
AB  - A method of analysis is presented for estimating the magnitude of a treatment
      effect among compliers in a clinical trial which is asymptotically unbiased and
      respects the randomization. The approach is valid even when compliers have a
      different baseline risk than non-compliers. Adjustments for contamination (use of
      the treatment by individuals in the control arm) are also developed. When the
      baseline failure rates in non-compliers and contaminators are the same as those
      who accept their allocated treatment, the method produces larger treatment
      effects than an 'intent-to-treat' analysis, but the confidence limits are also
      wider, and (even without this assumption) asymptotically the efficiencies are the
      same. In addition to providing a better estimate of the true effect of a
      treatment in compliers, the method also provides a more realistic confidence
      interval, which can be especially important for trials aimed at showing the
      equivalence of two treatments. In this case the intent-to-treat analysis can give
      unrealistically narrow confidence intervals if substantial numbers of patients
      elect to have the treatment they were not randomized to receive.

PMID- 9160498
TI  - Survival analysis in observational studies.
AB  - Multi-centre databases are making an increasing contribution to medical
      understanding. While the statistical handling of randomized experimental studies
      is well documented in the medical literature, the analysis of observational
      studies requires the addressing of additional important issues relating to the
      timing of entry to the study and the effect of potential explanatory variables
      not introduced until after that time. A series of analyses is illustrated on a
      small data set. The influence of single and multiple explanatory variables on the
      outcome after a fixed time interval and on survival time until a specific event
      are examined. The analysis of the effect on survival of factors that only come
      into play during follow-up is then considered. The aim of each analysis, the
      choice of data used, the essentials of the methodology, the interpretation of the
      results and the limitations and underlying assumptions are discussed. It is
      emphasized that, in contrast to randomized studies, the basis for selection and
      timing of interventions in observational studies is not precisely specified so
      that attribution of a survival effect to an intervention must be tentative. A
      glossary of terms is provided.

PMID- 9160499
TI  - An unwelcome partner: parasitic choreography of the host cell cycle?

PMID- 9160500
TI  - Transmission factors for insect-vectored microorganisms.

PMID- 9160501
TI  - Genetic loose change: how retroelements and reverse transcriptase heal broken
      chromosomes.

PMID- 9160502
TI  - Rotaviruses in human and veterinary medicine.

PMID- 9160503
TI  - Vibrio cholerae serotype O139: swapping genes for surface polysaccharide
      biosynthesis.

PMID- 9160504
TI  - B cell longevity and immunological memory.

PMID- 9160505
TI  - The role of p53 in virally associated tumors.

PMID- 9160506
TI  - Intercellular communication and group behavior in bacteria.
AB  - Group behavior in bacterial populations requires intercellular communication,
      generally by means of self-produced signals. As the model system of bacterial
      quorum sensing demonstrates, the integration of these 'group' signals with other
      global regulators can lead to very complex and sophisticated interactions that
      are not necessarily limited to the signal-producing species alone.

PMID- 9160507
TI  - RNA editing in kinetoplastid parasites: what to do with U.
AB  - The editing of the mitochondrial RNAs of kinetoplastid protozoa is a bizarre form
      of transcript maturation that involves insertion and deletion of uridylate
      residues. Editing leads to the formation of translational initiation and
      termination codons, the correction of gene-encoded reading frame shifts and the
      creation of complete reading frames in mRNAs. It is therefore an essential step
      in mitochondrial gene expression.

PMID- 9160508
TI  - Oxazolidinones: new antibacterial agents.
AB  - The oxazolidinones are a new chemical class of synthetic antibacterial agents
      that are active orally or intravenously against multidrug-resistant Gram-positive
      bacteria. Their unique mechanism of action and activity against bacteria that
      pose therapeutic problems in hospital and community treatments make them
      promising candidates for antimicrobial agents.

PMID- 9160509
TI  - Apoptosis as a proinflammatory event: what can we learn from bacteria-induced
      cell death?
AB  - Infection of cells by some pathogenic bacteria triggers host cell apoptosis.
      Bacteria-induced apoptosis appears to promote an inflammatory response that
      causes tissue damage and further bacterial colonization. Shigella pathogenesis
      offers a paradigm for the role of apoptosis in bacterial infections.

PMID- 9160510
TI  - Did the inheritance of a pathogenicity island modify the virulence of
      Helicobacter pylori?
AB  - Strains of Helicobacter pylori from patients with peptic ulcer disease and
      gastric cancer contain a 40-kb fragment of DNA that is not present in isolates
      from carriers with asymptomatic infections. The discovery of the cag
      pathogenicity island suggests that virulence has evolved by quantum leaps through
      the inheritance of one or more DNA insertions.

PMID- 9160511
TI  - European contribution to the science, prevention and management of HIV infection.
AB  - The objectives of the European Commission Biomed AIDS Programme are to enable
      Europe to pool its intellectual and financial resources in the control, treatment
      and prevention of HIV infection and AIDS. In order to facilitate this aim the
      Commission has allocated 40 to 50 million ECU over the past 6 years for concerted
      action of the Biomed projects on AIDS by the countries of the European Union.
      This is only a small proportion of the real cost spent by the member countries on
      this epidemic.

PMID- 9160513
TI  - Molecular basis of the inefficacy and possible harmful effects of AIDS vaccine
      candidates based on HIV-1 envelope glycoprotein gp120.

PMID- 9160512
TI  - Urea/DTT solubilization of a recombinant Taenia ovis antigen, 45W, expressed as a
      GST fusion protein results in enhanced protective immune response to the 45W
      moiety.
AB  - Vaccination and challenge infection experiments were conducted in sheep using
      different forms of a recombinant protein (45W) from the cestode parasite Taenia
      ovis. 45W was expressed in Escherichia coli as a fusion protein with glutathione
      S-transferase (45W-GST) and was produced as both soluble protein and insoluble
      inclusion bodies. Vaccination of animals with either the soluble or inclusion
      body derived protein resulted in the immune response being predominantly directed
      to the GST moiety of 45W-GST. Conversely, vaccination with 45W-GST which had been
      solubilized/treated with urea and dithiothreitol (DTT), elicited enhanced
      responses to the 45W moiety and significantly reduced responses to GST.
      Vaccination with all forms of 45W-GST protected sheep against experimental T.
      ovis infection. However, protection was highly correlated with anti-45W antibody
      levels and these were significantly higher in animals vaccinated with the
      urea/DTT treated form of 45W-GST. It is suggested that recombinant proteins
      expressed either with or without fusion partners may stimulate enhanced immune
      responses when incorporated in vaccine formulations in a denatured/reduced state.

PMID- 9160514
TI  - Controlled release microparticles as a single dose hepatitis B vaccine:
      evaluation of immunogenicity in mice.
AB  - Hepatitis B surface antigen (HBsAg) was encapsulated in microparticles prepared
      from polylactide-co-glycolide (PLG) and polylactide (PLA) polymers using a
      solvent evaporation process. The immunoreactivity of the entrapped antigen was
      investigated by SDS-PAGE and Western blot. The microencapsulation process was
      modified to obtain both small (< 10 microns) and large microparticles (10-100 <
      microns). 80% of the antigen was encapsulated. Various combinations of small and
      large microparticles with controlled release characteristics were investigated in
      CD1 mice. Groups of animals were immunized with 30 micrograms equivalent of HBsAg
      in microparticles per animals. The control group received, three injections of 10
      micrograms of HBsAg on alum at 0, 1 and 6 months. Results indicated that a single
      injection of HBsAg in microparticles could maintain the antibody response at a
      level comparable to the three-injection alum schedule for at least 1 year. An in
      vitro inhibition assay was developed to demonstrate that antigen-antibody
      reactivity were comparable for the microparticle immunized mice and the alum
      immunized mice. A competition assay with a monoclonal antibody specific for the
      neutralizing epitope of HBsAg demonstrated comparable binding for the sera from
      the microparticle and alum immunized mice.

PMID- 9160515
TI  - Multiple antigen constructs (MACs): induction of sterile immunity against
      sporozoite stage of rodent malaria parasites, Plasmodium berghei and Plasmodium
      yoelii.
AB  - We prepared multiple antigen constructs (MACs) using circumsporozoite (CS)
      protein-based B-epitopes from Plasmodium berghei, (PPPPNPND)2 and Plasmodium
      yoelii, (QGPGAP)3QG, along with a P. berghei T-helper epitope KQIRDSITEEWS. Mice
      were immunized with individual MACs in oil-in-water or water-in-oil vehicles
      containing block copolymer (P1005) and detoxified RaLPS (RaLPS) as well as other
      adjuvants. Sporozoite challenge results demonstrated that MACs in adjuvant could
      induce antibodies capable of active and passive protection. Water-in-oil vaccines
      induced the highest level of protection in mice immunized with either P. berghei
      or P. yoelii MACs. In a study aimed at co-eliciting immunity against P. berghei
      and P. yoelii, three immunizations with MACs induced protective antibodies
      against P. berghei but not P. yoelii parasite challenge. Therefore, it can be
      concluded that individually MACs are capable of inducing strong and protective
      immune responses to either species of rodent malaria, and that protection can be
      passively transferred. When MAC formulations were used together as a combined
      vaccine, P. berghei MACs induced a strong protective antibody response while P.
      yoelii MACs induced a weaker nonprotective response.

PMID- 9160516
TI  - A chain section containing epitopes for cytotoxic T, B and helper T cells within
      a highly conserved region found in the human immunodeficiency virus type 1 Gag
      protein.
AB  - Cell-mediated immune responses constitute a major defense against the spread of
      human immunodeficiency virus type 1 (HIV-1). However, multiple alterations within
      a particular epitope may accumulate during disease progression, allowing the
      virus to escape cytotoxic T lymphocytes (CTLs). Therefore, the best candidate for
      a peptide vaccine that would prevent the onset of the disease might be a chain
      section containing epitopes for the generation of CTLs in regions of conserved
      sequences among different HIV-1 isolates. We previously showed that immunizing
      mice with synthetic peptides consisting of 23-amino acids (Gag-23mer; 287-309
      amino acid residues) in a highly conserved region derived from the major core
      protein p24 of HIV-1 generates specific CTLs as well as antibodies. Here, we
      identified one CTL (T-1; 291-300) and two B-cell (B-1; 290-299 and B-2; 300-309)
      epitopes, all of which consisted of 10 amino acids within the region. In
      addition, helper T cells primed by the Gag-23mer peptide were proliferated by in
      vitro stimulation with a 21mer (H-1; 289-309) or a 19mer (H-2; 291-309) peptide,
      but not with a 17mer peptide (293-309) or 19mer peptide (287-305). Immunization
      with the H-1 peptide generated an antibody reactive to B-1, but not B-2, whereas
      that with H-2 generated an antibody reactive to B-2, but not B-1. CTLs were not
      generated by immunization with these peptides, indicating that the entire
      sequence of Gag-23mer is the helper epitope for CTLs. Thus, the Gag-23mer is a
      chain section containing epitopes for cytotoxic T, B and helper T-cells within a
      highly conserved region of HIV-1 Gag protein.

PMID- 9160517
TI  - A clearer distinction between HIV-1 paired isolates from peripheral blood
      mononuclear cells of asymptomatic carriers with and without CD8+ T-cells at nef
      rather than env V3 loci.
AB  - In asymptomatic carriers, the vast majority of human immunodeficiency virus type
      1 (HIV-1) infection is non-productive whilst the clinical stage of disease is
      associated with significant virus expression. Virus-specific CD8+ T-cell
      functions are believed to play a major role in the generation of heterogeneous
      virus populations and in subsequent disease progression. Here, we prepared two
      types of HIV-1 isolate by culturing whole and CD8+ T cell-depleted peripheral
      blood mononuclear cells (PBMCs) from five asymptomatic carriers. The former is
      expected to be escape variant populations, whereas the latter would be mixed
      populations including the former viruses. The analyses of Nef and Env V3 sequence
      variations of viruses in a total of 77 and 44 DNA clones, respectively, allowed a
      direct comparison to be made of the differences between the paired isolates.
      Comparison of Nef sequences between the paired isolates showed them to be more
      distinct in two carriers with a relatively stable CD4/CD8 ratio (Nos 68 and 69),
      than in two other carriers with similar CD4/CD8 ratios (Nos 53 and 57), or in
      carrier No. 67, which had an extremely lower CD4/CD8 ratio. By contrast, a
      distinction between the paired isolates by use of the Env V3 sequences was only
      apparent in the latter three carriers. These results indicate that the
      predominant populations of HIV-1 in Nos 68 and 69 were sensitive to selective
      pressure from Nef-specific CD8+ T-cells, while those in Nos 53, 57, and 67 were
      sensitive to pressure from V3-specific CD8+ T-cells. It is noteworthy that Nos 53
      and 57 progressed to an AIDS-related complex shortly and several years after this
      examination. These data suggest that HIV-1-induced pathogenesis is more strongly
      associated with the generation of variant nef alleles than with env V3 variants,
      and that these arise by CD8+ T-cell pressure.

PMID- 9160518
TI  - The efficiency of antigen delivery from macrophage phagosomes into cytoplasm for
      MHC class I-restricted antigen presentation.
AB  - Macrophages can present exogenous antigen in association with MHC class I
      molecules. Indirect evidence indicates that antigens internalized by phagocytosis
      can enter cytoplasm before following the conventional MHC class I presentation
      pathway. However, little is known about how common such entry is, or to what
      extent it depends on the kind of particle ingested. This study reports
      quantitative and morphological characterization of antigen delivery from
      phagosomes into cytoplasm for MHC class I-restricted antigen presentation.
      Ovalbumin (OVA) was associated with polystyrene particles (PS), biodegradable
      poly-e-caprolactone particles (PCL), and sheep red blood cells (SRBC), and its
      delivery into macrophage cytoplasm, via phagocytosis was assessed with a T
      hybridoma assay for MHC class I-restricted presentation of OVA-derived peptides.
      Although direct introduction of antigen into cytoplasm by scrape-loading produced
      the most efficient presentation, comparable signals could be obtained after
      phagocytosis of PCL or PS. Phagocytosis of OVA-loaded SRBC, and OVA internalized
      by pinocytosis, did not deliver efficiently. MHC class I-restricted presentation
      of phagosome-derived OVA required cytoplasmic processing, as it was inhibited by
      proteasome inhibitors and brefeldin A. Morphological studies showed that
      biotinylated OVA originating in PCL phagosomes could be delivered into the
      cytoplasm of 90% of the macrophages. These results indicate that phagocytosis per
      se is not sufficient to deliver antigen into cytoplasm, but that phagocytosis of
      solid, synthetic polymeric particles delivers antigen efficiently into cytoplasm
      for MHC class I processing.

PMID- 9160519
TI  - Simulation studies of vaccination strategies in African horse sickness.
AB  - A simulation model including two hosts (horses and donkeys) and one vector
      (Culicoides imicola) for African horse sickness in Spain is extended to consider
      vaccination strategies. If hosts were protected prior to virus introduction,
      elimination of simulated epidemics was related nonlinearly to the fraction
      protected. Protecting donkeys as well as horses increased the effectiveness of
      vaccination. Prevention of 50% of epidemics required 75% coverage of horses and
      donkeys or 90% coverage of horses only. Protection after the introduction of the
      virus was rarely successful in preventing outbreaks. If horses alone were
      protected, the number of donkeys was the most significant factor determining the
      level of protection needed to prevent an epidemic. If both hosts were protected,
      the abundance of other hosts for vector blood meals was the most significant
      factor. These results suggest that prophylactic vaccination of both horses and
      donkeys with high coverage is necessary to prevent outbreaks of African horse
      sickness in Spain.

PMID- 9160520
TI  - Adjuvants influence the quantitative and qualitative immune response in BALB/c
      mice immunized with respiratory syncytial virus FG subunit vaccine.
AB  - The ability of monophosphoryl lipid A (MPL), QS-21 and alum to alter the
      immunologic response to immunization with respiratory syncytial virus a chimeric
      FG construct (FG) subunit vaccine was examined in BALB/c mice. FG/MPL, FG/alum,
      and FG/MPL/QS-21 combinations increased non-neutralizing antibody response, while
      FG/QS-21 did not. FG subunit vaccine with MPL, QS-21, or both had cytokine
      responses more closely resembling primary infection than FG/alum, with decreased
      interleukin-4 mRNA levels and increased IgG2a isotype antibody. The lungs of the
      mice immunized with FG subunit vaccines showed a heightened inflammatory response
      to respiratory syncytial virus challenge as compared to live virus immunization.
      Adjuvants can be used to alter the humoral and cellular responses to RSV subunit
      immunization.

PMID- 9160521
TI  - Intranasal Sendai virus vaccine protects African green monkeys from infection
      with human parainfluenza virus-type one.
AB  - Human parainfluenza virus-type I (hPIV-1) infections are a common cause of
      "group" and hospitalizations among young children. Here we address the
      possibility of using the xenotropic Sendai virus [a mouse parainfluenza virus
      (PIV)] as a vaccine for hPIV-1. Sendai virus was administered to six African
      green monkeys (Cercopithecus aethiops) by the intranasal (i.n.) route. A long
      lasting virus-specific antibody response was elicited, both in the serum and
      nasal cavity. Sendai virus caused no apparent clinical symptoms in the primates,
      but live virus was detected in the nasal cavity for several days after
      inoculation. No virus was detected after a second dose of Sendai virus was
      administered on day 126 after the initial priming. Animals were challenged with
      hPIV-1 i.n. on day 154. All six vaccinated animals were fully protected from
      infection while six of six control animals were infected with hPIV-1. The
      antibody responses induced by Sendai virus immunizations proved to be greater
      than those induced by hPIV-1. These results demonstrate that unmanipulated Sendai
      virus is an effective vaccine against hPIV-1 in a primate model and may
      constitute a practical vaccine for human use.

PMID- 9160522
TI  - The effect of Syntex adjuvant formulation (SAF-m) on humoral immunity to the
      influenza virus in the mouse.
AB  - Syntex adjuvant in its microfluidized form (SAF-m) was equal to or superior to
      Freund's complete adjuvant in stimulating an enhanced hemagglutination inhibition
      (HI) antibody response in mice to trivalent influenza virus vaccine (TIV). There
      was an average 16-fold increase in HI titer for the three components of the
      vaccine with no significant differences among strains. The increased serum
      antibodies correlated with an increase in protection against infection. The
      threonyl-MDP (t-MDP) component of the adjuvant played no role in this activity.
      The vehicle, in contrast, was so effective that it could be diluted 1:202 (in the
      presence of (t-MDP) and still retain a statistically significant effect. Vaccine
      and adjuvant could be stored together at 4 degrees C for 2 years without a
      statistically significant change in potency. Mice were given a priming
      immunization with TIV, PBS, or adjuvanted TIV (AIV). A year later, the mice were
      boosted with heterotypic TIV or AIV. The nature of the priming immunization made
      no difference in the strong antibody response to an AIV boost. However, priming
      significantly improved the response to TIV with AIV being the best primer. The
      enhancement in the antibody response to AlShanghai of the unprimed (PBS) elderly
      mice caused by AIV (14-fold improvement over TIV) was similar to that in young
      mice. Female mice had antibody titers which overall were 2.6-fold higher than
      those of males (P < 0.0001) for AIV and TIV.

PMID- 9160523
TI  - Inoculation of plasmids expressing the dengue-2 envelope gene elicit neutralizing
      antibodies in mice.
AB  - To develop a nucleic acid vaccine against dengue type-2 virus, the PreM and 92%
      of the envelope (E) genes were cloned into different eukaryotic plasmid
      expression vectors (pkCMVint Polyli and pVR1012). The resultant plasmid
      constructs (pD2ME and P1012D2ME) properly expressed the truncated E protein in
      vitro as evidenced by the expected protein size on SDS-PAGE and the ability of
      the protein to be recognized by monoclonal antibodies directed against
      conformational epitopes. Three-week-old BALB/c mice were given intradermal
      inoculations of each construct. Plasmid expression vectors without dengue genes
      were used as controls. One hundred percent of the mice that received the pD2ME
      and p1012D2ME constructs developed anti-dengue antibodies. These antibodies were
      shown to neutralize dengue type-2 virus in vitro. This is the first demonstration
      of the use of nucleic acid inoculation in the development of potential dengue
      virus. vaccines.

PMID- 9160524
TI  - DNA immunization can stimulate florid local inflammation, and the antiviral
      immunity induced varies depending on injection site.
AB  - DNA immunization is being considered to augment, or even to supplant, more
      traditional methods of antiviral immunization. Different routes of administration
      lead to markedly different levels of marker protein expression, but only limited
      data are available concerning the antiviral responses induced by DNA inoculated
      by different routes, and their protective efficacy. In this report we evaluate
      antiviral immunity induced by inoculation of DNA by the intramuscular (i.m.) and
      intradermal (i.d.) routes, and make three novel observations. First, i.d.
      immunization is dose-dependent and, although not uniformly successful, can induce
      very high levels of cytotoxic T lymphocyte (CTL) activity, varying dependent on
      the vehicle in which the DNA is administered. Second, while antiviral immunity
      induced by i.m. DNA injection has been demonstrated by many groups, we show
      herein a marked difference in immunity depending on the muscle injected. Immunity
      induced by DNA injection of the anterior tibial muscle significantly exceeds that
      induced following injection of the quadriceps muscle as judged by three criteria,
      namely CTL induction, decrease in virus titer following nonlethal challenge, and
      survival following a normally lethal challenge dose of virus. Thirdly, we
      evaluate the local immune response induced following immunization with DNA
      encoding a viral antigen. We show that, when recipients are already immune to the
      encoded protein, a severe but localized inflammatory response may result.

PMID- 9160525
TI  - Augmentation of cell-mediated immunotherapy against herpes simplex virus by
      interleukins: comparison of in vivo effects of IL-2 and IL-7 on adoptively
      transferred T cells.
AB  - We investigated the ability of human recombinant interleukin-7 (IL-7) to enhance
      cytotoxic T lymphocyte (CTL) activity in vivo using mice infected with herpes
      simplex virus type-1 (HSV-1). IL-7 or interleukin-2 (IL-2) was administered twice
      daily to immune naive mice subjected to adoptive transfer of immune T cells after
      infection with HSV-1. The immunotherapeutic effect was measured by detecting the
      virus recovered from pinna. Administration of HSV-1 immune T cells to naive mice
      significantly increased their ability to clear the virus. Twice-daily injections
      of IL-7 at 200 IU provided an additional 20-fold reduction in virus load,
      compared with T cell therapy alone (P < 0.0005). Combining IL-2 and T cell
      therapy provided about a sevenfold reduction compared with T cell therapy alone
      (P < 0.0009). IL-7 also enhanced the antiviral effects of T cell therapy against
      HSV-1 through the enhancement of CD8+ CTLs, as observed with IL-2. These results
      indicate that IL-7 may be used adjunct to adoptive T lymphocyte therapy in
      modulating human viral diseases and cancer through enhanced immune T cell
      activities.

PMID- 9160526
TI  - Development of an adjuvant-active nonionic block copolymer for use in oil-free
      subunit vaccines formulations.
AB  - Nonionic block copolymers, synthesized from repeating units of oxypropylene and
      oxyethylene, can be designed so that individual copolymers have unique physical
      properties with differential levels of adjuvant activity. We have designed high
      molecular weight block copolymers that spontaneously assemble into 500 nm-3 mum
      particles when formulated with protein antigens in aqueous solutions at
      physiological pH. The adjuvant activity of one of these copolymers, termed
      CRL1005, was compared to selected research adjuvants using ovalbumin (OVA) as the
      prototype vaccine antigen. Suboptimal doses of OVA were formulated with complete
      and incomplete. Freund's adjuvant (CFA/IFA), alum Quil-A saponins Ribi Adjuvant
      System (RAS) or the CRL1005 copolymer and these formulations were used to
      immunize C57BL/6 mice. The CRL1005 copolymer appeared to be more potent than
      either Quil-A or alum and comparable to the RAS formulation, based on the numbers
      of responding mice and the OVA-specific antibody titers. Alum. RAS and Quil-A all
      augmented the production of IgG1 and IgG2l, similarly whereas only the CFA/IFA
      boosted IgG2a levels significantly. The effect of adjuvants on relative antibody
      affinity was more variable with the CRL1005 and CFA/IFA inducing antibodies with
      the highest affinity scores. This high molecular weight nonionic copolymer is
      nontoxic in aqueous formulations and should therefore be compatible with a wide
      variety of protein or polysaccharide vaccine antigens.

PMID- 9160527
TI  - Persistence of humoral immunity to rabies 1100 days after immunization and effect
      of a single booster dose of rabies vaccine.
AB  - Forty-four vaccinees immunized with rabies vaccine and human rabies
      immunoglobulin according to the abbreviated intramuscular regimen (the 2-1-1
      schedule) were followed-up after 1100 days and had their blood samples taken. The
      persistence of rabies neutralizing antibody was proven in the sera of all
      vaccinees. 56% of whom demonstrated titres > or = 0.5 IU ml-1. At the same day
      the vaccinees were given a single booster dose of vaccine whose effect was
      measured 2 weeks later. With the RFFI test on day 1114, sera revealed an
      extraordinarily high booster response in all 44 vaccinees. The study proved the
      anamnestic response after a full course of rabies vaccination to be a very stable
      one, and the capability of a single booster dose of vaccine to evoke high-titred
      rabies antibody response. Of the four vaccines used in the study, under
      comparable conditions HDCV proved superior to PCECV PDEV and PVRV on all 3 days
      of serology-35, 1100 and 1114, though this difference was statistically attested
      only on days 35 and 1114.

PMID- 9160529
TI  - Vaccination campaign against hepatitis B for 12-year-old subjects in Italy.
AB  - The vaccination campaign against hepatitis B for 12-year-old subjects in Italy
      was evaluated in 136 health districts (USL); 55 in the north, 69 in the centre,
      and 12 in the south, respectively. Out of the 113,230 eligible subjects born in
      1981, 105, 989, (93.6%) completed the three dose series during the period 1993
      1994. However, wide geographical differences are observed: the acceptance rate
      was as high as 97.9% (range 89.7-100.0) and 96.6% (range 76.0-100.0) in the north
      and in the centre, respectively; but only 65.1% in the south (range 26.8-100.0).
      Subjects were recruited in the north and in the centre mostly from the list of
      residents, while in the south more likely only from the list of people attending
      school. The school attendance in the south, not as good as in the other Italian
      areas, particularly among people belonging to a subgroup of the population
      economically disadvantaged, appears to be a strong determinant of the different
      vaccine coverage observed. Active efforts from health services in southern areas
      are necessary to reach subgroups of population who escape hepatitis B vaccination
      and who are also at high risk of HBV infection.

PMID- 9160528
TI  - Monoclonal immunoglobulin A antibody to the major outer membrane protein of the
      Chlamydia trachomatis mouse pneumonitis biovar protects mice against a chlamydial
      genital challenge.
AB  - In order to analyze the protective role that IgA may play in a chlamydial
      infection two IgA monoclonal antibodies (mAb), MoPn 4-2 and MoPn 13-2, were
      raised against the major outer membrane protein (MOMP) of the Chlamydia
      trachomatis mouse pneumonitis (MoPn) biovar. mAb MoPn 4-2 was found to be serovar
      specific while mAb MoPn 13-2 was species specific. mAb MoPn 4-2 recognized a
      surface exposed conformational epitope as shown by its ability to bind to native
      EBs and nonreduced MOMP while failing to bind to heat and trypsin treated EBs, to
      reduced MOMP and to synthetic MOMP peptides. In contrast, mAb MoPn 13-2
      recognized a nonconformational epitope since it was able to bind treated EBs, to
      reduced MOMP and to the synthetic peptide MTTWNPTISGSGI located in variable
      domain 4 of the MOMP. Both mAbs agglutinated intact EBs and had in vitro
      neutralizing activity. However, mAb MoPn 4-2 had a 20-fold higher in vitro
      neutralizing ability when compared to mAb MoPn 13-2 (50% neutralization at 5
      micrograms ml-1 vs 100 micrograms ml-1). In an in vitro in vivo infectivity
      assay, mAb MoPn 4-2 protected mice against infertility when C. trachomatis MoPn
      elementary bodies were preincubated with the mAb before inoculation. In addition,
      passive transfer of mAb MoPn 4-2 resulted in significant protection as measured
      by a decrease in the number of mice infected, and in the intensity and duration
      of vaginal shedding. These results support previous findings suggesting that IgA
      antibodies can play a role in protection against a chlamydial infection, and
      further encourage work to develop vaccination strategies that elicit mucosal
      immunity.

PMID- 9160530
TI  - Meat safety consequences of implementing visual postmortem meat inspection
      procedures in Danish slaughter pigs.
AB  - The consequences of a change from a traditional meat inspection procedure,
      including manual handling, palpation and incision, to an entirely visual
      postmortem meat inspection procedure in Danish slaughter pigs were assessed by a
      comparative study of the two methods in 183,383 slaughter pigs. Out of 58 lesion
      codes (selected with a prevalence > or = 5.5 x 10(-5)), 26 (45 per cent) were
      assessed either as merely aesthetic or as the healed stage of an earlier lesion
      and nine (15 per cent) as active, but local processes, occurring only in non
      edible tissue. Five lesion codes (9 per cent) were assessed as active, non
      abscessal processes occurring in edible tissue, caused by swine-specific
      pathogens and 10 (17 per cent) were abscessal or pyaemic lesions occurring in
      edible tissue. Seven lesion codes (12 per cent) may be associated with consumer
      health hazards (two frequently and five rarely), and one with occupational health
      hazards. It was estimated that per 1000 carcases, an additional 2.5 with
      abscessal or pyaemic lesions (in edible tissue) containing Staphylococcus aureus,
      4 x 10(-4) containing ochratoxin, 0.2 with arthritis due to Erysipelothrix
      rhusiopathiae, 0.1 with caseous lymphadenitis, 0.7 faecally contaminated with
      Salmonella species, and 3.4 faecally contaminated with Yersinia enterocolitica
      would remain undetected as a result of changing from the traditional to the
      visual inspection procedure. Two valuable reasons for implementing a visual
      control system are the potential for decreased cross-contamination (no handling,
      cutting and incision) and reduced inspection costs. The resources released as a
      result may be reallocated to hygiene and surveillance programmes.

PMID- 9160531
TI  - Enzymuria as an index of renal damage in canine leishmaniasis.
AB  - Urinary enzyme activities of alanine aminopeptidase, gamma-glutamyl
      transpeptidase, alkaline phosphatase, N-acetyl-beta-D-glucosaminidase and beta
      glucuronidase were determined in 15 dogs with leishmaniasis and in a group of
      eight normal dogs. Serum creatinine and blood urea nitrogen concentrations were
      also measured and renal histology was examined. All the affected dogs had renal
      lesions. However, no significant differences in blood urea nitrogen and
      creatinine concentrations were found between the control group and the affected
      group. The urinary enzyme activities of gamma-glutamyl transpeptidase (P < 0.01),
      N-acetyl-beta-D-glucosaminidase (P < 0.01) and beta-glucuronidase (P < 0.05) were
      significantly higher in the affected dogs. Urinary enzymes therefore seem to be a
      more sensitive and reliable test for assessing early renal damage in canine
      leishmaniasis than serum creatinine or blood urea nitrogen concentrations.

PMID- 9160532
TI  - Glaucoma in a captive-bred great horned owl (Bubo virginianus virginianus).
AB  - A captive-bred adult great horned owl (Bubo virginianus virginianus) behaved as
      though it was bilaterally blind. An ophthalmological examination showed that it
      had an increased intraocular pressure in both eyes and gonioscopy showed an
      abnormality of the iridocorneal angles. Retinal changes were also observed.
      Treatment was not attempted and the owl was euthanased. Histopathology confirmed
      the abnormal iridocorneal angles, but the exact aetiology of the primary glaucoma
      was not identified.

PMID- 9160533
TI  - Caprine arthritis-encephalitis virus: detection of proviral DNA in lactoserum
      cells.

PMID- 9160534
TI  - Within-herd BHV-1 prevalence prediction from an ELISA on bulk milk.

PMID- 9160535
TI  - Hard decisions on TB.

PMID- 9160536
TI  - Worming of dogs in mid-Wales for Echinococcus granulosus.

PMID- 9160538
TI  - Investing in veterinary medicines.

PMID- 9160537
TI  - Unexplained sporadic milk drop in dairy cows.

PMID- 9160539
TI  - Testing the suffocation false alarm theory of panic disorder.
AB  - The need for hypotheses concerning the nature of those functions that have been
      impaired in stereotyped psychiatric syndromes is emphasized. With regard to panic
      disorder, the key role of the spontaneous panic attack became apparent from
      several viewpoints. However, panics seem to be a type of misreleased fear, which
      guided the thinking concerning the nature of possible psychological or
      physiological malfunctions. We indicate that spontaneous panic cannot be fear,
      but must represent some other malfunction and suggest that the spontaneous panic
      is a suffocation false alarm. The development of this idea is outlined, and
      attempts to develop tests of this hypothesis are indicated. In particular,
      studies of children with congenital central hypoventilation syndrome, patients
      with Chronic Obstructive Pulmonary Disease, dyspnea, field measures of panic,
      pregnancy, childbirth and the postpartum period, as well as the premenstrual
      syndrome afford pointed opportunities, new information and potential tests of the
      theory. A recent challenge to the theory from acetazolamide infusion is
      discussed. Developing a possible antecedent for the pathologically depressed
      threshold for the suffocation alarm, in the form of a phasic endorphinergic
      deficiency, is presented.

PMID- 9160540
TI  - Noise stress and the development of benzodiazepine dependence in the rat.
AB  - Rats housed in conditions of noise stress were given daily injections of diazepam
      (4 mg/kg). Significant tolerance developed to the sedative effects within 5 days
      of treatment, as measured by head dipping and motor activity in the holeboard and
      by the number of closed arm entries in the plus-maze. These results are in
      agreement with other reports of rapid tolerance to sedative effects. However, in
      contrast to the usual finding of tolerance to anxiolytic actions after 2-3 weeks
      of treatment, in this study no tolerance developed after 23 days of treatment to
      diazepam's anxiolytic effects in the plus-maze. On withdrawal from the 23 days of
      diazepam treatment, there was no anxiogenic response in the plus-maze. Therefore,
      it seems that when chronic administration of diazepam is accompanied by chronic
      stress, tolerance does not occur to the anxiolytic effects, although it does
      develop to the sedative effects.

PMID- 9160541
TI  - Safety signals and human anxiety: a fear-potentiated startle study.
AB  - The effect of a safety signal on the magnitude of anticipatory anxiety was
      investigated using the fear-potentiated startle reflex paradigm in humans. The
      amplitude of the acoustic startle reflex was measured during the anticipation of
      unpleasant electric shocks ("threat") and during "safe" conditions. Threat and
      safe conditions were signaled by three different colored lights. Two lights
      signaled safe conditions (safe 1, safe 2) and the other light signaled the threat
      condition (threat). In phase I, the lights alternated, each presentation
      consisting of one colored light. In phase II, the lights were presented alone or
      in the two combinations of safe 1 (or safe 2) + threat and safe 1 + safe 2. In
      both phases, the contingency between the lights and the shock was explained to
      the subjects. It was emphasized that no shock could be administered when the safe
      1 and threat light were simultaneously presented in phase II. Subjects' belief
      and understanding of the instructions were verified. In Phase I, startle was
      increased in the threat-alone compared to the safe-alone condition, reflecting
      increased anticipatory anxiety in the threat-alone condition. In phase II,
      startle in the safe + threat condition was smaller than in the threat-alone
      condition, but was larger than in the safe + threat. These results were
      interpreted as suggesting that the threat signal was still able to elicit
      anticipatory anxiety despite the fact that it was no longer associated with a
      threat.

PMID- 9160542
TI  - Serum cytokine and soluble interleukin-2 receptors in patients with panic
      disorder.
AB  - There has been very little research investigating the interface between panic
      disorder and the immune system. This preliminary study explores the relationship
      between panic disorder and serum levels of cytokines, which have potent immune
      and central nervous system activity, and soluble interleukin-2 receptors, a well
      known marker of T-cell activation. Fifteen women with panic disorder and 19
      healthy female subjects had serum levels of interleukin-1, interleukin-2, and
      soluble interleukin-2 receptors (SIL-2Rs) measured by enzyme-linked immunoassay.
      Women with panic disorder had slightly increased serum levels of interleukin-2
      but did not differ from age-comparable and gender-matched controls in serum
      interleukin-1 alpha, or interleukin-1 beta. And although the mean SIL-2R levels
      were not different for the two groups, the SIL-2R levels were present across a
      wider range of values in the women with panic disorder. Our data suggest that
      more extensive investigation of circulating levels of interleukin-2 and the
      soluble interleukin-2 receptor in patients with panic disorder may be warranted.

PMID- 9160543
TI  - Resting cardiovascular measures in patients with panic disorder and social phobia
      and health control subjects: relationship to habitual exercise frequency.
AB  - Weekly aerobic exercise frequency was evaluated and compared to resting
      cardiovascular measures in 22 patients with panic disorder, 11 patients with
      social phobia and 24 healthy control subjects. There were no diagnostic
      differences in resting cardiovascular activity or levels of habitual aerobic
      exercise. However, it was evident that, regardless of diagnostic status,
      individuals who participated in regular aerobic exercise (20 minutes duration at
      a minimum frequency of 2x/week) had lower heart rate and higher vagal tone than
      those who did not exercise aerobically. Implications for previous and future
      reports of resting cardiovascular measures in anxiety disorder patients are
      discussed.

PMID- 9160544
TI  - Consistencies between recalled panic and lactate-induced panic.
AB  - This study investigated the frequency and severity of symptoms during naturally
      occurring panic attacks recollected as "usual" and during sodium lactate-induced
      attacks. Seventy-six male and 126 female patients with panic disorder or
      agoraphobics with panic attack (DSM-III criteria) underwent lactate infusion
      studies and were serially administered the Acute Panic Inventory (API). Fifty
      nine percent of the subjects were rated by an attending psychiatrist to have
      experienced lactate-induced panic attacks. Patients were also asked to API
      symptom rate their "usual" panic attacks. For panic recollected as usual, the
      most frequently reported symptoms (> or = 75%) at the moderate to severe levels
      included: afraid in general, difficulty concentrating, difficulty performing a
      job, desire to flee, afraid of losing control, palpitations, feeling hot or cold
      or both, dyspnea, dizzy-lightheaded. During lactate infusion, 25 of 29 API
      symptoms increased significantly from prelactate to point of panic; however,
      particularly robust effect sizes were exhibited for the desire to flee, dyspnea,
      tingling, twitching/trembling and difficulty doing a job. Comparison of panic
      recollected as usual and lactate-induced panic showed that more than half of the
      symptoms did not differ after Bonferroni correction; however, the most notable
      were fear in general, dyspnea, chest pain/discomfort, difficulty swallowing,
      feeling weak, desire to flee, and feeling hot/cold or both. These data point to a
      very distinctive role during both recollected and lactate-induced panic attacks
      for fearfulness the desire to flee (by definition), and for dyspnea, difficulty
      performing a job and fear of losing control. During lactate-induced panic,
      dyspnea exhibited the most robust effect size of all physical symptoms.

PMID- 9160545
TI  - Decline in serum lactate levels over time.

PMID- 9160547
TI  - Growth hormone response to clonidine in the nervous pointer dog model of anxiety.
AB  - Blunted growth hormone responses to clonidine have been reported in most studies
      of humans with panic disorder but have been an inconsistent finding in the study
      of other anxiety syndromes. The growth hormone response to oral clonidine (100
      micrograms/kg) was investigated in the adult nervous pointer dog, a genetic
      animal model of anxiety. Compared with placebo, clonidine produced significant
      increases in plasma levels of growth hormone; however, there were no differences
      in the growth hormone (GH) responses to clonidine in the nervous compared with
      the normal pointer dogs. Findings in this animal model are discussed within the
      context of noradrenergic-hypothalamic-GH dysfunction reported in some but not all
      types of anxiety disorders in humans.

PMID- 9160546
TI  - Panic attacks, complex partial seizures, and multiple meningiomas.
AB  - A 39-year-old woman presented with typical panic disorder symptoms of two years
      duration. Imipramine (IMI) treatment yielded complete remission of her symptoms
      for three years. At that time, however, her symptoms recurred. Neither increasing
      the IMI dose nor an adequate trial of fluoxetine controlled her symptoms. Further
      history revealed subtle changes in her symptoms suggestive of complex partial
      seizures. Scalp EEG was normal, but an MRI revealed multiple meningiomas. Her
      symptoms remitted completely on carbamazepine. This case illustrates the
      phenomenologic overlap between panic attacks and complex partial seizures, and a
      neuroanatomic overlap between the two syndromes is hypothesized.

PMID- 9160548
TI  - Serum interleukin-2 and soluble interleukin-2 receptor levels in generalized
      social phobia.
AB  - Alternations in immune function have been described in a variety of psychiatric
      disorders including schizophrenia and depression; however, we do not know of any
      research involving social phobia and the immune system. This preliminary study
      explores the relationship between social phobia and two well-established immune
      parameters, serum interleukin-2 (IL-2) levels, a potent immune and central
      nervous system modulator, and soluble interleukin-2 receptors (SIL-2Rs), a well
      known marker of T-cell activation. Fifteen subjects with generalized social
      phobia and 15 healthy volunteers had serum IL-2, and SIL-2Rs measured by enzyme
      linked immunoassay. Subjects with social phobia and normal volunteers had similar
      mean serum IL-2 and SIL-2R levels. The data suggest that, unlike other
      psychiatric disorders, these immune measures may not be used to differentiate
      patients with generalized social phobia from normal volunteers.

PMID- 9160549
TI  - Lactate-induced anxiety after imipramine and diazepam treatment.
AB  - To examine the effect of treatment on lactate-induced anxiety in a controlled
      study, we infused 44 panic disorder patients with lactate and placebo before and
      after eight weeks of double-blind treatment with imipramine, diazepam, or
      placebo. During treatment, both imipramine and diazepam groups improved more than
      the placebo group. After treatment, patients in both the imipramine and diazepam
      groups had significantly less anxiety than the placebo patients when reinfused
      with lactate. In addition, imipramine decreased posttreatment panic attack
      frequency and diazepam decreased the perceived severity of posttreatment lactate
      induced panic attacks. This study demonstrates that diazepam, like imipramine, is
      an effective treatment for panic disorder, and that both imipramine and diazepam
      blunt lactate-induced anxiety in a placebo controlled study.

PMID- 9160550
TI  - Patient Stage of Change predicts outcome in a panic disorder medication trial.
AB  - OBJECTIVE: The authors test the hypothesis that patient readiness to change
      predicts outcome in a placebo-controlled medication trial. METHOD: Out-patients
      with panic disorder and agoraphobia completed the Stages of Change (SOC)
      questionnaire, a measure of readiness to change, before being randomly assigned
      either sustained release (SR) adinazolam or placebo in a 4 week double-blind
      trial. RESULTS: In the "intent to treat" analysis, for the 202 subjects who made
      at least one visit after baseline, adinazolam SR was significantly more effective
      than placebo on most major outcome measures. Of the 126 subjects who completed
      the SOC questionnaire, regression analyses showed significant correlations
      between SOC scores and all 5 outcome measures. In a second analysis, cluster
      membership based on SOC scores was predictive of outcome on 3 of 5 measures. In
      each statistical analysis, subjects who were not predisposed to change as
      measured by the SOC were significantly less likely to change. CONCLUSIONS:
      Patient readiness to change was strongly correlated with outcome in a placebo
      controlled panic disorder trial with an effective medication. In this study, the
      SOC category, Precontemplation (i.e., those subjects who reported the belief that
      they had no problem) were less likely to change compared to those who believed
      that they had a problem.

PMID- 9160551
TI  - The Numbing Scale: psychometric properties, a preliminary report.
AB  - This study explored the psychometric properties of a new self-report instrument,
      The Glover Numbing Scale. The scale measures a variety of behaviors reported by
      individuals experiencing an inability to access feelings other than hostility and
      rage. The scale was administered to inpatient Vietnam combat veterans with post
      traumatic stress disorder (PTSD, n = 323), PTSD diagnosed Veterans Affairs (VA)
      outpatient and veterans' outreach center veterans (n = 208), two Vietnam veteran
      noncombat groups (n = 45), two psychiatric noncombat controls (anxiety disorder,
      n = 40; major depressive disorder, n = 31), and a nonpsychiatric never-in-Vietnam
      veteran control group (n = 48). Reliability information suggested that the scale
      was internally consistent with good test-retest correlations. Convergent and
      discriminant validations were assessed based on the pattern of the scale's
      correlations with relevant Minnesota Multiphasic Personality Inventory (MMPI)
      scales. The contrasting pattern of correlations provided by a subgroup of
      veterans who reported always feeling dead or shut down was highlighted. Principal
      component analysis resulted in a five factor solution that provided evidence for
      the scale's factorial validity. Numbing Scale scores discriminated levels of
      psychopathology within the veteran population. PTSD outreach center veterans' sum
      scores and item scores on the Numbing Scale were more similar to responses of
      anxiety disorder patients than to major depressive disorder patients. Overall,
      the findings strongly support the clinical application of the Numbing Scale.

PMID- 9160552
TI  - Social anxiety and perception of early parenting among American, Chinese
      American, and social phobic samples.
AB  - Emotionally distant and controlling child-rearing attitudes have been reported to
      characterize the parents of American or western European social phobics in
      previous research. However, the notion that these parental attitudes may be
      associated with social anxiety only in some cultures has not been investigated.
      The present study examined social anxiety among American social phobics and
      American and Chinese/Chinese American volunteer samples and how it may relate to
      their parents' child-rearing attitudes. Multivariate analyses of variance
      revealed overall group differences. Both volunteer samples reported lower levels
      of anxiety than social phobics. Parents of Chinese/Chinese Americans and social
      phobics were reported to be similar in their (1) isolation of children from
      social activities; (2) over-emphasis of others' opinions; and (3) use of shame
      tactics for discipline (more so than American volunteers' parents). However,
      parents of nonsocial phobics were more likely to attend family social activities
      than social phobics' parents. Overall, the association between a reported
      parenting style emphasizing others' opinions and shame tactics and social anxiety
      in their adult children was more evident in both American samples than among
      Chinese/Chinese Americans.

PMID- 9160553
TI  - Social rhythm in anxiety disorder patients.
AB  - The social rhythm metric (SRM) is a self report diary instrument which generates
      a numerical measure of rhythmicity of daily life behaviors. Depression
      researchers have proposed that life events cause disruption of social rhythmicity
      and this leads to disturbance in the sense of well-being and to disruption of
      physiologic rhythmicity known to be related to depressive episodes. We
      hypothesized that low rhythmicity of daily activities might also be
      characteristic of anxiety disorder patients. SUBJECTS: Forty-eight patients who
      met DSM III-R criteria for an anxiety disorder were recruited and compared with
      41 previously monitored normal controls. PROCEDURES: All patients and controls
      completed at least two weeks of daily monitoring with the SRM. Anxiety patients
      underwent structured diagnostic assessment and completed demographic and clinical
      rating scales. SRM was analyzed according to a previously developed algorithm.
      RESULTS: Anxiety disorder patients report significantly lower regularity of daily
      activities than normal controls. The low SRM scores were not accounted for by the
      presence of comorbid affective disorder. CONCLUSIONS: We identify a new type of
      abnormality in anxiety disorder patients which has potential clinical as well as
      theoretical interest.

PMID- 9160554
TI  - Response to alcohol in social phobia.

PMID- 9160555
TI  - Prevalence of respiratory diseases in patients with panic and obsessive
      compulsive disorders.

PMID- 9160556
TI  - Are gonadotrophic hormonal factors perceived to be important by women with panic
      attacks?

PMID- 9160557
TI  - Parapsychological phenomena and anxiety disorders.

PMID- 9160558
TI  - High-dose subchronic imipramine treatment: effects on anxiety-like (conflict)
      behavior in rats.
AB  - In the management of both anxiety and depression, agents such as imipramine (IMI)
      are noted for their 3-5 week delay to onset of clinical effect. A similar delay
      to onset has been reported for the anxiolytic-like (i.e., anticonflict) effect of
      chronic IMI treatment (2.5 mg/kg, BID for 5 weeks) in the Conditioned Suppression
      of Drinking (CSD) conflict paradigm; similar effects have been reported with
      other antidepressants and in other conflict procedures. In contrast, in the
      Forced Swim Test (FST) model of depression, antidepressant-like effects are
      reported immediately following subchronic treatment with relatively high doses of
      these agents (e.g., 30 mg/kg IMI, 3 times in 24 hr). The present study examined
      the effects of this high-dose, subchronic treatment with IMI on CSD conflict
      behavior. Conflict-trained female Sprague Dawley rats were divided into three
      groups with comparable pretreatment baselines for shocks received. Treatments (0,
      15, and 30 mg/kg IMI) were administered intraperitoneally (IP) at 23, 5, and 1 hr
      prior to CSD conflict testing on day 1; CSD conflict behavior was then monitored
      daily (Mon-Fri) for 5 weeks following treatment. IMI treatment (30 and, to a
      lesser extent, 15 mg/kg) significantly reduced shocks received (punished
      responding) and water intake (unpunished responding) on day 1; although water
      intake was also slightly reduced in both IMI treatment groups for the remainder
      of test week 1, there was no difference in shocks received between the various
      treatments for this period. Subjects receiving 30 mg/kg IMI (but not those
      receiving 15 mg/kg IMI or vehicle) accepted significantly more shocks than
      controls on weeks 2-4 (maximal increase at week 3) and returned to pretreatment
      baseline levels by week 5. Thus, subchronic high-dose treatment with IMI (and
      perhaps other antidepressants) produces anxiolytic-like effects which are delayed
      in nature and persist for several weeks after treatment.

PMID- 9160560
TI  - Dot-probe evaluation of cognitive processing biases in patients with panic
      disorder: a failure to replicate and extend.
AB  - A number of cognitive psychology paradigms have been used to demonstrate that
      panic disorder patients selectively process stimuli that are related to themes of
      physical threat and catastrophe. The present investigation was an attempt to
      replicate and extend initial findings obtained with the dot-probe paradigm, a
      visual attention paradigm which allows for the assessment of allocation of visual
      attention to stimuli of varied emotional valence via the measurement of detection
      latencies for visual probes that follow their presentation. Twenty-two panic
      disorder patients and 20 healthy control subjects were tested using neutral,
      social threat, and panic symptom/fear cues. No between-group differences were
      observed in detection latencies for visual probes that followed neutral, social
      threat, or panic symptom/fear cues. These results represent a failure to
      replicate previous reports of selective processing in panic disorder and suggest
      that panic disorder patients may not selectively process cues related to bodily
      sensation and panic-related fears. Implications of this finding are discussed.

PMID- 9160559
TI  - Assessment instrument for panic disorder that includes fear of sensation
      producing activities: the Albany Panic and Phobia Questionnaire.
AB  - A set of items was developed to assess fear of activities which produce physical
      sensations (e.g., exercise) based on clinical observations that individuals with
      panic disorder fear such activities in addition to agoraphobic situations. Factor
      analysis of a 32-item pool based on responses from 438 subjects confirmed three
      distinct factors which were labelled: agoraphobia, social phobia, and
      interoceptive fears. Evidence was obtained to support the internal consistency,
      test-retest reliability, and construct validity of all three factors.
      Importantly, the interoceptive factor demonstrated a slightly different pattern
      of relationships with other constructs to the agoraphobic factor, even though the
      two were highly related. The present questionnaire will help to expand current
      assessments of panic disorder for both clinical work and research.

PMID- 9160561
TI  - Pilot MRI study of brain size in nervous pointer dogs.

PMID- 9160562
TI  - Etiological beliefs and treatment preferences in anxiety-disordered patients.

PMID- 9160563
TI  - Lactic acid response to caffeine in panic disorder: comparison with social
      phobics and normal controls.

PMID- 9160565
TI  - Klein's suffocation false alarm theory: another perspective.

PMID- 9160564
TI  - Pilot study of a CCKB antagonist in patients with panic disorder: preliminary
      findings.
AB  - L-365,260 is a CCKB antagonist which has been shown to completely prevent CCK-4
      induced symptoms of panic attack in single-dose (50 mg) placebo-controlled
      studies in patients with panic disorder. The present report is data from one site
      (n = 38) in a multicenter study (n = 88) designed to assess the preliminary
      efficacy and safety of L-365,260 in patients meeting DSM-III-R criteria for panic
      disorder, with or without agoraphobia. In order to participate, male and female
      patients were between 18-55 years of age and in good physical health. Following a
      one-week single-blind placebo lead-in, patients were randomized to 30 mg four
      times daily of L-365,260 (n = 18; 7 M, 11 F) or placebo (n = 20; 9 M, 11 F) for
      six weeks. At end of study, none of the efficacy measures, including the
      frequency of panic attacks, the Physician's Global Improvement Scale, and the
      Hamilton Rating Scale for Anxiety, were significantly improved over baseline
      values. L-365,260 was well-tolerated; the most common drug-related adverse events
      were headache and lightheadedness. Further testing of L-365,260 at higher
      dosages, or testing of other CCKB antagonists, is required to rule out the
      usefulness of this novel treatment approach.

PMID- 9160566
TI  - Is simple screening effective in detecting cases of obsessive-compulsive disorder
      and post-traumatic stress disorder?

PMID- 9160567
TI  - Course and outcome in panic disorder: a review of recent follow-up studies.
AB  - This paper reviews the methodologic considerations that are important in
      evaluating and interpreting panic disorder outcome studies and the results of the
      most well-designed of these studies. Sixteen studies that used modern diagnostic
      criteria and interviewed at least 25 patients on at least two occasions over a
      minimum follow-up period of one year are reviewed. Results show that, despite the
      availability of effective anti-panic treatments, panic disorder remains a chronic
      illness. While most patients improve, few are "cured." The presence of
      agoraphobia, major depression and personality disorder seems to predict poorer
      outcome. The importance of measuring multiple clinical dimensions of panic is
      emphasized, along with the need to reach a consensus about the definition of
      "outcome" and the particular instruments to use to measure it.

PMID- 9160568
TI  - Dose-response effects of intravenous caffeine in normal volunteers.
AB  - The administration of caffeine has been developed as a chemical model for the
      study of anxiety. However, previous researchers investigating caffeine-induced
      anxiety states in humans have administered oral caffeine. In this dose-response
      study, we investigated the effects of blindly administered intravenous caffeine
      (3, 5, and 7 mg/kg) versus placebo in normal control subjects. We report the
      first series of subjects experiencing olfactory hallucinations (10 of 10
      subjects, 24 of 30 infusions) immediately following intravenous caffeine
      infusion. In addition, consistent with our previous work with oral caffeine, we
      found dose-related increases in ratings of anxiety and blood levels of cortisol
      and lactate. One subject experienced a DSM-III-R panic attack. Further
      questioning revealed that his mother suffers panic attacks. Our findings of
      olfactory hallucinations are discussed within the context of localized limbic
      system dysfunction, noting the phenomenologic and possible neuroanatomic overlap
      between panic disorder and complex partial seizures.

PMID- 9160569
TI  - Pharmacotherapy of post-traumatic stress disorder with a novel psychotropic.
AB  - This was a multicenter, randomized, double-blind, parallel trial conducted in
      outpatients in three countries. Following screening and placebo washout, patients
      received brofaromine (a combined MAO-A inhibitor/5-HT transport inhibitor) or
      placebo in a flexible dosing design. Based upon the CAPS, a standardized post
      traumatic stress disorder (PTSD) interview, findings from a cohort involving both
      subchronic and chronic traumatic stress marginally favored brofaromine over
      placebo; however, not to a statistically significant degree. With a more
      conservation definition of the syndrome, employing a primary cohort of patients
      with PTSD of one year or greater duration, brofaromine significantly reduced PTSD
      symptoms in comparison with placebo. In all analyses a substantial proportion of
      patients in both drug and placebo groups remained symptomatic throughout.
      Findings were supported by an analysis of secondary measures. Brofaromine may be
      of benefit in the therapy of PTSD.

PMID- 9160570
TI  - Antecedents of neurosis in a cohort of 30,344 twins in Sweden.
AB  - We analyzed questionnaire survey responses in a cohort of 30,344 twins in Sweden,
      280 of whom became inpatients due to neurosis within the subsequent 10 years. As
      a group, they differed substantially in their reported health profile from the
      survey responders who were not admitted for psychiatric treatment. When
      subclassified into anxiety, depressive, and other neuroses, these were
      indistinguishable from each other regarding self-perceived health and personality
      traits. Women were more likely to be hospitalized for neurosis. These mental and
      social antecedents for both anxiety and depression are in keeping with the
      concept of a shared diathesis which is supported by neurophysiological, treatment
      and genetic epidemiological studies.

PMID- 9160571
TI  - Familial transmission of panic disorder: effect of major depression comorbidity.
AB  - This study assesses the effect of major depressive disorder (MDD) comorbidity on
      familial transmission of panic disorder (PD). The following questions are
      addressed: (1) is PD familial, i.e., do relatives of patients with PD show an
      increased risk for PD? (2) do PD and MDD share a common diathesis, i.e., do
      relatives of patients with PD without MDD show an increased risk for MDD? (3) is
      lifetime comorbid PD with MDD conjointly familial, i.e., do relatives of patients
      with PD and MDD show an increased risk for the combined syndrome? Subjects were:
      (1) 152 relatives of 54 anxiety clinic patients with PD and MDD; (2) 193
      relatives of 72 patients with PD without MDD; (3) 231 relatives of 77 not ill
      controls. Relatives were interviewed by clinicians, and best estimate DSM-III-R
      diagnoses were formulated by senior staff. Relatives of PD with MDD (13%) and PD
      without MDD probands (9%) showed significantly higher rates of PD than relatives
      of controls (3%). Relatives of PD with MDD probands (37%) showed significantly
      higher rates of MDD than relatives of PD without MDD (24%) and controls (21%),
      with no difference between the latter two groups. Relatives of PD with MDD
      probands (9%) showed significantly higher rates of PD with MDD than relatives of
      PD without MDD (3%) and controls (1%). We conclude that: (1) PD is familial; (2)
      PD in the absence of MDD does not incur increased risk of MDD to relatives; and
      (3) PD with MDD may represent a distinct, complex syndrome.

PMID- 9160572
TI  - Clinical characteristics of familial generalized anxiety disorder.
AB  - The authors seek to determine whether the clinical characteristics of generalized
      anxiety disorder (GAD) differ in individuals with a high vs. low familial
      vulnerability to illness. We identified 486 personally interviewed female twins
      from a population-based register who had both an interviewed co-twin and a
      lifetime history of GAD using modified DSM-III-R criteria which required a one
      month minimum duration of illness. We attempted to predict risk for GAD in the co
      twin from the clinical features of the GAD in the proband twin using the Cox
      proportional hazard model, controlling for year of birth and zygosity. Only two
      variables uniquely predicted an increased risk for GAD in the co-twin: number of
      GAD symptoms endorsed and comorbidity with bulimia. Variables that did not
      uniquely predict risk of illness in the co-twin included age at onset, duration
      of the longest episode and number of episodes. The familial vulnerability to GAD
      can be meaningfully indexed by clinical features of the syndrome. These results
      suggest that if the syndrome of GAD is to be narrowed, it would, from a familial
      perspective, be more valid to increase the minimum number of required symptoms
      rather than to increase the minimum duration of illness.

PMID- 9160573
TI  - Natural killer cell activity in patients with panic disorder.

PMID- 9160574
TI  - Sertraline in social phobia.
AB  - Eleven consecutive SCID-diagnosed generalized social phobias without major
      depression, other prominent anxiety disorders, substance abuse, alcoholism or
      organic mental disorder, were treated, open label, with sertraline up to 200 mg
      daily for 12 weeks. There were seven completers. Of these, five showed
      substantial improvement, after being on sertraline 100 mg daily for two weeks
      (following no response to sertraline 50 mg daily for four weeks). There were few
      side effects among the completers. The four dropouts complained of side effects
      and loss of interest in continuing treatment. Final average dose for completers
      who responded was 170 mg daily.

PMID- 9160575
TI  - Neurocognitive function in panic disorder and social phobia patients.
AB  - A neuropsychological test battery designed to assess verbal learning and memory,
      visual memory, psychomotor speed, cognitive flexibility and concentration was
      administered to patients with panic disorder (N = 18) and social phobia (N = 18)
      and a group of healthy control subjects (N = 16). Overall, the neurocognitive
      performance of the panic disorder and social phobia patients was lower than that
      of control subjects. Analyses of the verbal test variables indicated reduced
      performance in panic disorder and social phobia patients, relative to control
      subjects, on measures of verbal learning and memory. In addition, panic disorder
      patients exhibited deficits on short-delay free recall. No group differences were
      observed on tests of visual memory, psychomotor speed, cognitive flexibility, and
      concentration. These results, while indicative of diminished neuropsychological
      test performance in patients with panic disorder and social phobia, do not
      suggest the presence of syndrome-specific or localized neurocognitive deficits.

PMID- 9160576
TI  - Tic-related vs. non-tic-related obsessive compulsive disorder.
AB  - Obsessive compulsive disorder (OCD) is a chronic condition characterized by an
      array of intrusive, upsetting thoughts and interfering, repetitive behaviors.
      Some forms of OCD may be etiologically related to Tourette's syndrome (TS). This
      cross-sectional study examines a range of obsessive compulsive (OC) symptoms
      which have been hypothesized to distinguish tic-related OCD from non-tic-related
      OCD. One hundred and seventy-seven patients with a primary DSM-IIIR diagnosis of
      OCD, aged 16 to 72, participated in the study. Patients with tic-related OCD (n =
      56) reported more OC symptoms, including more aggressive, religious, and sexual
      obsessions as well as checking, counting, ordering, touching, and boarding
      compulsions than did patients with non-tic-related OCD (n = 121). Contrary to our
      expectation, these two groups of OCD patients did not differ with regard to the
      presence of "just right" phenomena or symptoms of psychasthenia. "Just right"
      phenomena and symptoms of psychasthenia, however, were both found to be
      associated with the current severity of OC symptoms.

PMID- 9160577
TI  - Neuroendocrine responsivity to monoaminergic system probes in generalized social
      phobia.
AB  - We examined neuroendocrine correlates of central monoamine function in patients
      with the generalized type of social phobia compared to healthy volunteers in
      order to test hypotheses of dopaminergic, noradrenergic, and/or serotonergic
      dysregulation in patients with this disorder. A double-blind, placebo-controlled,
      neuropharmacological challenge study was performed using probes for the
      serotonergic (fenfluramine), dopaminergic (levodopa), and noradrenergic
      (clonidine) systems. Twenty-one patients with DSM-III-R social phobia
      (generalized type) and 22 "never mentally ill" volunteers participated in the
      study after providing informed consent. Patients with social phobia had an
      augmented cortisol response to fenfluramine administration compared to the
      volunteers. In contrast, we found that neither the prolactin response to
      fenfluramine, the growth hormone or norepinephrine response to clonidine, nor the
      prolactin or eye-blink responses to levodopa, differed between patients with
      social phobia and healthy volunteers. The findings suggest that patients with
      social phobia may exhibit selective supersensitivity of serotonergic systems, but
      that dopaminergic and noradrenergic function appear normal. Further challenge
      studies with more specific serotonin probes before and after treatment may assist
      in the clarification of the pathophysiology of social phobia.

PMID- 9160578
TI  - Pharmacological challenge test of the Tridimensional Personality Questionnaire in
      patients with social phobia and normal volunteers.

PMID- 9160579
TI  - Preliminary look at the effects of pregnancy on the course of panic disorder.

PMID- 9160580
TI  - Clonazepam-related sexual dysfunction in male veterans with PTSD.
AB  - Medication-induced sexual dysfunction can significantly interfere with patients'
      quality of life and lead to poor compliance. This retrospective study examined
      the records of 100 male veterans with post-traumatic stress disorder (PTSD)
      selected in alphabetical order from an active treatment file of 230 patients.
      Forty-two patients had received clonazepam (mean maximum dose: 3.4 +/- 1.6
      mg/day) at some point during their treatment. Of these, 18 (42.9%) complained of
      significant sexual dysfunction (primarily erectile dysfunction). Eighty-four
      patients received diazepam (mean maximum dose: 52.1 +/- 29.7 mg/day), nine
      received alprazolam (mean maximum dose: 5.2 +/- 2.8 mg/day) and eight received
      lorazepam (mean maximum dose: 3.8 +/- 2.4 mg/day). None of these patients
      complained of sexual dysfunction during treatment with these three other
      benzodiazepines. Our findings suggest that benzodiazepines, particularly
      clonazepam in the current study, can be a cause of sexual dysfunction in many
      male patients. Prospective studies comparing the overall clinical utility of
      various benzodiazepines are indicated in this and other clinic populations.

PMID- 9160581
TI  - Development of anxiety symptoms during a deep diving experiment.
AB  - Six commercial divers were investigated for anxiety responses during a 29-day,
      open-sea world record dive at 500 meters of depth. Three of six (50%) divers
      developed anxiety. The authors emphasize the importance of research on
      personality traits as possible predictors for the development of anxiety during
      deep dives of exceptional depth and duration of confinement.

PMID- 9160582
TI  - Single-site findings in a study of the safety and efficacy of a CCKB receptor
      antagonist, CI-988, in the treatment of generalized anxiety disorder.

PMID- 9160583
TI  - Increased mRNA for corticotrophin releasing hormone in the amygdala of fawn
      hooded rats: a potential animal model of anxiety.
AB  - Compared to the outbred Wistar rat strain, the Fawn-hooded rat strain has several
      characteristics which suggest that the Fawn-hooded strain is hyperaroused. Fawn
      hooded rats exhibit more freezing behavior in response to stress, have an
      increased preference for alcohol, develop adult onset hypertension, and have
      elevated urinary catecholamine levels. We used quantitative in situ hybridization
      to investigate central components of the corticotropin releasing hormone (CRH),
      arginine vasopressin (AVP) and noradrenergic stress response and arousal systems
      in these rats. We also measured basal corticosterone levels and adrenal weights
      to assess tonic hypothalamic-pituitary-adrenal axis activity. Compared to Wistar
      rats, Fawn-hooded rats had significantly increased CRH mRNA in the central
      nucleus of the amygdala and reduced CRH mRNA in the paraventricular nucleus of
      the hypothalamus. Fawn-hooded rats also bad reduced AVP mRNA expression in the
      parvocellular cells of the hypothalamic paraventricular nucleus. There were no
      differences between strains in glucocorticoid receptor mRNA in the hippocampus or
      the paraventricular nucleus or in mineralocorticoid receptor mRNA in the
      hippocampus. There was also no difference between strains in tyrosine hydroxylase
      mRNA in the locus ceruleus. Finally, adrenal weights were significantly reduced
      in the Fawn-hooded rats while basal corticosterone levels were similar in the two
      strains, which suggests central hypoactivity of the hypothalamic-pituitary
      adrenal axis in Fawn-hooded rats compared to Wistar rats. Increased CRH mRNA in
      the central nucleus of the amygdala and reduced tonic hypothalamic-pituitary
      adrenal axis activity may play a role in the unique behavioral and physiological
      characteristics of Fawn-hooded rats.

PMID- 9160584
TI  - Peptides and anxiety: a dose-response evaluation of pentagastrin in healthy
      volunteers.
AB  - A large body of data suggest that brain cholecystokinin (CCK) systems are
      involved in the regulation of anxiety, and numerous studies have demonstrated
      that CCK-4, a CCKB agonist, reliably induces panic attacks in patients with panic
      disorder. Recently, pentagastrin, a commercially available CCKB agonist, has been
      reported to have similar anxiogenic properties. To further explore the utility of
      pentagastrin as a challenge agent and to determine whether its effects are dose
      related, a dose-response study was conducted in ten healthy volunteers.
      Pentagastrin (0.2 microgram/kg, 0.6 microgram/kg and 1.0 microgram/kg) and
      inactive placebo were infused over one minute on four separate challenge days in
      a double-blind fashion. Subjects received pentagastrin while participating in a
      structured social interaction task. Repeated measures of anxiety, blood pressure,
      pulse, ACTH, and cortisol were taken at baseline and postinfusion. Pentagastrin
      administration led to increases in anxiety, pulse, ACTH, cortisol and physical
      symptoms of panic, in a dose-related manner. Participation in the social
      interaction task led to increases in measures of anxiety as well as increases in
      pulse and blood pressure. Few differences were found between the 0.2 microgram/kg
      dose of pentagastrin and placebo, or between the 0.6 microgram/kg and the 1.0
      microgram/kg doses of pentagastrin. These findings support the notion that CCK
      systems are involved in the regulation of anxiety, and suggest that the 0.6
      microgram/kg dose may be optimal for increasing symptoms of anxiety while
      minimizing unpleasant side effects. The powerful anxiogenic effects of the social
      interaction task underscore the importance of contextual variables in challenge
      studies.

PMID- 9160585
TI  - Patterns of obsessive compulsive symptoms in Tourette subjects are independent of
      severity.
AB  - Studies have examined the expression of obsessive compulsive (OC) symptoms in
      obsessive compulsive disorder (OCD), OCD with co-occurring Tourette's Syndrome
      (TS) or chronic motor tic disorder (CMT) and TS alone. In adult samples, there
      appears to be a relatively consistent OC symptom thematic content that
      characterizes OCD alone and OCD in conjunction with tics or TS. Previous studies
      have controlled for the severity of OC symptoms in OCD and TS groups. In the
      current study, it was our objective to determine whether patterns of OC symptoms
      in TS are independent of OC symptom severity. The current exploratory study
      examined OC symptom expression in a nonclinically based TS sample with a broad
      range of OC symptoms and severity and a selected clinical OCD sample without
      TS/tics. Univariate and multivariate statistical analysis explored patterns of OC
      symptom expression between the two groups. Similar to previous reports examining
      OC symptoms in OCD and OCD with TS/tics, subjects with OCD alone were
      characterized by contamination obsessions and cleaning compulsions. In contrast,
      TS subjects had more somatic, sexual and symmetry obsessions and more checking,
      counting and touching/blinking compulsions, independent of OC symptom and tic
      severity. A discriminant function using obsessive items alone correctly grouped
      91.4% of cases. The current study replicates patterns of OC symptom expression
      unique to OCD alone. Patterns of OC symptoms, in particular obsessive symptoms,
      can robustly predict membership in OCD or TS groups, even with a substantial
      variation in OC symptom severity as measured by the Y-BOCS score.

PMID- 9160586
TI  - Single ion gas chromatographic/mass spectroscopic quantitative analysis of
      environmental CO2 in agoraphobic environments.

PMID- 9160587
TI  - Growth hormone response to clonidine and L-dopa in normal volunteers.

PMID- 9160588
TI  - Treatment of social phobia with fluoxetine.

PMID- 9160589
TI  - Double-blind pilot trial of desipramine versus fluoxetine in panic patients.

PMID- 9160590
TI  - Sertraline in the treatment of patients with social phobia.

PMID- 9160591
TI  - Comparison of anxiety sensitivity in panic disorder and social phobia.

PMID- 9160592
TI  - Panic disorder in subjects with pure mania and depressive mania.

PMID- 9160593
TI  - Anxiety among widowed elders: is it distinct from depression and grief?
AB  - The purpose of this study was to test the validity and utility of distinguishing
      symptoms of anxiety from those of depression and grief in recently spousally
      bereaved elders. We also examined pathways from baseline (six months or less post
      spousal death) to follow-up (12 and 18 months post-death) levels of anxiety,
      depression and grief-related symptoms. Baseline and follow-up data were available
      from 56 recently widowed elderly subjects recruited for an investigation of
      physiological changes in bereavement. Confirmatory factor analyses indicated that
      a model in which anxiety was specified as a third factor, apart from depression
      and grief factors, fit the data well and significantly better than either the one
      or two factor models. Path analyses revealed that both baseline severity of grief
      and anxiety had significant lagged effects and predicted follow-up severity of
      depression. Symptoms of anxiety appeared distinct from those of depression and
      grief, and the anxiety, depression and grief factors differentially predicted
      subsequent symptomatology. These findings suggest a need for more specific
      identification and treatment of anxiety, depression and grief symptoms within the
      context of late-life spousal bereavement.

PMID- 9160594
TI  - Long-term course and outcome in panic disorder: a naturalistic follow-up study.
AB  - Fifty-five of 102 consecutively evaluated patients with panic disorder seen in
      consultation at a specialty anxiety and mood disorders clinic were reinterviewed
      from 15 to 60 months later after naturalistic treatment in the community. Over
      the follow-up period, most patients displayed improvement in panic attack
      frequency and severity, phobic avoidance, depression, and major role functioning,
      although only five (10%) were asymptomatic on all measures at follow-up. The
      majority of patients with impaired interpersonal functioning showed no
      improvement on this measure. Thirty percent of the patients were panic-free at 12
      months and 28% at the time of follow-up, with 43% experiencing at least three
      panic-free months during the follow-up period. Comorbid agoraphobia, major
      depression, and Axis II disorders were associated with worse outcome on selected
      measures of symptomatic and functional impairment. However, the strongest
      predictors of overall improvement were avoidance coping for outcome at 12 months
      and Axis I comorbidity for outcome at the time of the follow-up evaluation.

PMID- 9160595
TI  - What predicts improvement and compliance during the behavioral treatment of
      obsessive compulsive disorder?
AB  - The aim of the study was to identify factors associated with treatment compliance
      and clinical improvement when obsessive compulsive disorder is treated with
      graded exposure and response prevention. The sample consisted of all patients
      with a diagnosis of obsessive compulsive disorder admitted over a 3-year period
      to a unit specialising in behavioral treatment. All subjects were diagnosed using
      reliable diagnostic criteria and all were followed-up for 12 months. A range of
      social and clinical variables was examined using stepwise regression analysis.
      Treatment compliance was associated with being employed during treatment and
      living with one's family. Clinical improvement was associated with never having
      been treated previously, being employed during treatment, having a fear of
      contamination, having overt ritualistic behaviour, the absence of depression and
      living with one's family.

PMID- 9160596
TI  - Social, blood/injury, and agoraphobic fears in patients with physically
      unexplained chronic pain: are they clinically significant?
AB  - Recently, there has been increased interest in the extent to which chronic pain
      patients fear and avoid activities that are thought to be related to the
      experience of pain. To date, however, few studies have evaluated the nature and
      extent of nonpain fears in these patients. The purpose of the present study was
      to address this paucity. The Fear Questionnaire was administered to 130 patients
      with physically unexplained chronic pain and 93 patients with a chronic condition
      unrelated to pain. Results indicated that the chronic pain patients were more
      fearful and avoidant of social interactions/situations and blood/injury than were
      the patient controls. Agoraphobia was minimal and did not differ significantly
      between groups. As well, the proportions of chronic pain patients indicating
      definite avoidance of particular situations related to blood/injury phobia (i.e.,
      injection/minor surgery, hospitals, sight of blood, and thoughts of
      injury/illness) and social phobia (i.e., being watched/stared at, and
      speaking/acting to an audience) were significantly greater when compared to the
      patient controls. These results indicate that nonpain fear and avoidance are
      common in patients with chronic pain. Implications regarding the significance of
      these fears and avoidance behaviours on the experience and maintenance of pain
      symptoms and related disability are discussed.

PMID- 9160597
TI  - Anxiety sensitivity and treatment outcome in panic disorder.
AB  - The purpose of this study was to examine the relationship between change in
      anxiety sensitivity, as measured by the Anxiety Sensitivity Index (ASI), and
      treatment outcome in a sample of 106 subjects with a DSM-III-R diagnosis of panic
      disorder (with or without agoraphobia) who were participants in an evaluation
      study of cognitive-behavioral treatment. Results revealed that subjects who
      received active treatment had significantly lower anxiety sensitivity scores at
      post-treatment than the wait-list control group. We also examined change in
      anxiety sensitivity from pre- to post-treatment in reference to Clinical Global
      Improvement (CGI) ratings and with the effect size statistic. Subjects who showed
      improvement based on CGI ratings also demonstrated a reduction in anxiety
      sensitivity. Furthermore, the effect sizes obtained with the ASI were greater in
      magnitude than those obtained with other widely used anxiety self-report
      measures. Taken together, the finds supported the use of the Anxiety Sensitivity
      Index as a treatment outcome measure in panic disorder research.

PMID- 9160598
TI  - Method for assessing the duration of therapeutic action and milligram equivalence
      of anxiolytics.

PMID- 9160599
TI  - Four-dimensional Anxiety and Depression Scale: a preliminary psychometric report.

PMID- 9160600
TI  - Inositol treatment of post-traumatic stress disorder.

PMID- 9160602
TI  - Efficacy of clomipramine in obsessive-compulsive disorder.

PMID- 9160601
TI  - Treatment of Koro and panic attacks after stroke.

PMID- 9160603
TI  - Panic disorder and social phobia: possible implications of comorbid depression
      for drug therapy.
AB  - Major depression is a common mental disorder with a lifetime prevalence of
      approximately 15% of the general population, affecting almost twice as many
      females as males. Panic disorder is a severe anxiety disorder with a lifetime
      prevalence of 2-3% or more. Like major depression, panic disorder affects nearly
      twice as many females as males. Both panic disorder and major depression are
      often chronic conditions, resulting in significant morbidity and mortality. Among
      patients who seek treatment for either panic disorder or major depression, both
      conditions are present in approximately one-third of the patient population.
      Substantial information suggests that individuals who suffer from both panic
      disorder and major depression respond poorly to acute treatment, are more likely
      to remain ill over the long term, require more psychiatric treatment, and are at
      approximately twice the risk of suicide attempts than individuals who suffer from
      either condition alone. There has been very little systematic study of
      individuals with coexisting panic disorder and major depression. This has left
      significant gaps in our knowledge about optimal treatment for the substantial
      subgroup of individuals suffering from both disorders simultaneously. Social
      phobia is a common disorder which affects 2-8% (females more than males) of the
      population. Recent advances in the pharmacological treatment of social phobia are
      reviewed. Patterns of comorbidity, effects of coexisting psychiatric disorders on
      disability, health care utilization and suicidality are discussed, together with
      treatment implications for coexisting social phobia and major depression.

PMID- 9160604
TI  - Comparison of RDC, DSM-III, DSM-III-R diagnostic criteria for generalized anxiety
      disorder.
AB  - The diagnosis of generalized anxiety disorder (GAD) has been controversial since
      its inception. It remains unclear whether more stringent diagnostic criteria,
      such as in DSM-III-R, have improved the validity of GAD. Family studies suggest
      that GAD aggregates at least weakly in families of probands with GAD, and support
      the separation of panic disorder (PD) and GAD. Therefore, we can use a family
      study design to examine the validity of GAD. Independent familial transmission of
      GAD supports the validity of GAD. We report here the risk of GAD according to
      RDC, DSM-III, and DSM-III-R criteria in the first-degree relatives of probands
      from four diagnostic groups: panic disorder, panic disorder with major
      depression, early-onset major depression (MDD), and normal controls. We did not
      find an elevated risk of DSM-III or DSM-III-R GAD in the relatives of any of the
      ill proband groups compared to the relatives of the never mentally ill when
      controlling for proband comorbidity for GAD. In contrast, RDC GAD aggregates in
      the first-degree relatives of probands from both of the PD proband groups (with
      and without MDD) compared to relatives of the normal control group. The inclusion
      of cases of subsyndromal panic attacks that did not meet the strict RDC for panic
      disorder as meeting the less restrictive RDC for GAD may partially account for
      the familial aggregation of RDC panic disorder and RDC GAD. RDC GAD seems to
      identify one or more syndrome(s) that may be on the familial spectrum of panic
      disorder. This syndrome may represent a mild or early variant of panic disorder.
      We also found a trend for RDC and DSM-III GAD to aggregate in the first-degree
      relatives of the MDD proband group compared to the relatives of the never
      mentally ill controls. These data suggest that GAD demonstrates more independent
      familial transmission from PD and MDD when defined by DSM-III-R criteria than
      when defined by RDC or DSM-III, and thus support the validity of DSM-III-R GAD.

PMID- 9160605
TI  - Somatotype in panic patients.
AB  - The aim of the study was to test whether an association exists between asthenic
      somatotype, as measured by the Quetelet index, and panic and or agoraphobia.
      Ninety-nine cases with panic and/or agoraphobia diagnosed at the psychiatric
      outpatient clinic of a general teaching hospital were compared to 99 controls
      with psychiatric conditions other than panic and agoraphobia, and to 64 medical
      controls, matched by age and gender. No differences in weight, height and raw
      Quetelet and ponderal indexes were found between panic cases and controls.
      However, 33.3% of cases, but only 19.2% of psychiatric controls and 18.7% of
      medical controls, were in the asthenic group as defined by the lower quartile of
      the Quetelet index (age and sex adjusted odds ratio = 2.33, 95% C.I.: 1.21-4.11).
      In the entire sample, the asthenic somatotype was associated with lower age and
      with the presence of hypermobility of joints. Since both panic disorder and
      mitral valve prolapse may be associated with the joint hypermobility syndrome
      (JHS), an inherited disorder of collagen synthesis, it is suggested that the
      relationship found between panic and asthenic somatotype might be mediated
      through JHS.

PMID- 9160606
TI  - Evidence for social phobia and other psychiatric disorders in adults who were
      growth hormone deficient during childhood.
AB  - We assessed the psychiatric status of 21 growth hormone deficient (GHD) adults
      who had been treated with growth hormone (GH) for short stature during childhood.
      Eight individuals (38%) were found to have undiagnosed social phobia. On a
      psychometric battery, the scores of GHD subjects with social phobia corresponded
      closely to those of a matched group of psychiatric patients with social phobia.
      Because these psychiatric symptoms have deleterious effects on quality of life,
      social function, and productivity, the physician should be alert to obtain
      psychiatric assessment of patients with GHD.

PMID- 9160607
TI  - Growth differences associated with compulsive and stereotyped behavior disorders
      in adults with mental retardation.
AB  - We have recently observed that compulsive behaviors in mentally retarded patients
      appear to be quite prevalent, can be reliably assessed, and have a high rate of
      co-occurrence with stereotyped and self-injurious behaviors in this population.
      As abnormal growth rate has been observed in obsessive-compulsive disorder (OCD)
      patients, we examined physical stature in adults with mental retardation who
      display repetitive movement disorders. Identification of cases with stereotypic
      movement disorder, and cases with compulsive behaviors was done using a symptom
      checklist and direct observation. Subjects with repetitive movement disorders
      were smaller in stature than control subjects, with gender differences observed
      across repetitive behavior disorders. Specifically, female subjects with
      compulsive behavior disorder, but not stereotypic movement disorder, were
      significantly shorter and weighted significantly less than same sex-matched
      controls. Conversely, male subjects with stereotypic movement disorder, but not
      compulsive disorder, were significantly shorter and weighed significantly less
      than same sex controls. These findings may point to a neuroendocrine abnormality
      associated with repetitive movement disorders.

PMID- 9160608
TI  - Personality dimensions in panic disorder before and after effective treatment.

PMID- 9160609
TI  - Cardio-respiratory and other symptom clusters in panic disorder.

PMID- 9160610
TI  - Anxiety symptoms in panic disorder and social phobia: support for suffocation
      theory of panic?

PMID- 9160611
TI  - Short-term rebound anxiolytic effects and long-term changes in platelet
      benzodiazepine binding after pentylenetetrazole-kindling in two strains of rat.
AB  - Although there were no differences in response to an acute injection of
      pentylenetetrazole (PTZ), there were strain differences in the development of
      kindled seizures to repeated injections (PTZ; 30 mg/kg 3 times weekly for 13
      injections), with Wistar rats reaching stage 4 or 5 of clonic-tonic seizures, but
      hooded Lister rats reaching only stage 2 or 3 of convulsive waves axially through
      the body. The strains also reacted differently to a test dose of PTZ (20 mg/kg)
      one week after the end of kindling, with the Wistar strain showing stage 3 and
      the Lister strain stage 2 seizures. When the rats were tested 24 h after the end
      of the kindling injections there was an anxiolytic effect in the social
      interaction test, in both the low light, familiar and the low light, unfamiliar
      test conditions that reached significance in the Wistar strain. The Wistar
      kindled rats showed an anxiolytic effect in the elevated plus-maze test of
      anxiety when they were tested 24 h after the end of kindling. The anxiolytic
      effects found 24 h after kindling could not be due to the seizure 24 h earlier,
      since no changes were found in rats tested 24 h after a single seizure from PTZ
      (60 mg/kg). When the rats were tested 1 week after the end of kindling there were
      no changes, compared with vehicle-injected controls, in either test of anxiety.
      There was no change in benzodiazepine binding in platelets of the kindled Lister
      rats but there was a significant increase in the kindled Wistar rats 1 week after
      the end of kindling and also 24 h after a single PTZ seizure. The pattern of
      increased platelet benzodiazepine binding did not correspond with the time course
      of rebound anxiolytic effects. However, after kindling it seems that there are
      long-lasting changes in benzodiazepine binding that are similar to the short-term
      increases that are found following a single seizure.

PMID- 9160612
TI  - Comparison of descriptive variables for symptomatic volunteers and clinical
      patients with anxiety disorders.
AB  - Worry about the generalizability of findings derived from clinical trials is a
      nagging problem. Because most clinical trials use individuals recruited by
      advertisements rather than patients solicited from clinical practice, bias in
      subject recruitment is a major concern. This paper compares and contrasts the
      demographic characteristics, symptomatologies, functional disabilities, health
      beliefs, and health expectations of clinical outpatients to those of subjects
      recruited from the media (symptomatic volunteers) for pharmacologic trials.
      Clinical patients were slightly younger, better educated, wealthier, and were
      more likely to be married. They had more recent exposure to benzodiazepines and
      antidepressants and were more likely to view their current condition as amenable
      to psychotherapy. They were more likely to feel that their symptoms would get
      worse without some type of treatment and to believe that treatment would cure
      them. The symptomatic volunteers had more presenting symptoms than the clinical
      patients. The two groups had similar Sheehan Disability Scale scores. These
      results suggest that further study is warranted of the characteristics of
      clinical patients and symptomatic volunteers.

PMID- 9160613
TI  - Hypervigilance in patients with obsessive-compulsive disorder.
AB  - The hypothesis that patients with obsessive-compulsive disorder (OCD) suffer from
      hypervigilant attention was investigated via explicit memory (incidental recall
      and recognition) and priming (reading speed) measures. OCD patients did not
      differ from normal controls on explicit measures of memory; specifically,
      recognition of unusual words (experiment 1) and recall and recognition of words
      and feature-specific information (experiment 2). Although both normal controls
      and OCD patients showed priming, the pattern of priming differed for the two
      groups (experiment 2). Specifically, patients with OCD failed to show feature
      specific priming, suggesting they may have attended more focally on the priming
      task than did normal controls. These findings support previous reports of normal
      performance in OCD on explicit memory tasks, but suggest more sensitive measures
      may reflect differences in processing information.

PMID- 9160614
TI  - Cognitive processing in post-traumatic stress disorder.
AB  - Recent research has suggested an abnormal attentional bias to threat in anxiety
      disorders. We have assessed the processing of thoughts of trauma, panic attacks,
      general fear and positive affect in a cohort of 15 war veterans with post
      traumatic stress disorder (PTSD) and an age- and sex-matched normal control
      group. Subjects with PTSD showed delayed processing of self-referential sentences
      when the themes of the sentences were traumatic experiences or positive affect,
      compared with controls. However, they were more efficient than control subjects
      in the processing of sentences describing situations of panic attacks and general
      fear. It would therefore appear that in patients with PTSD, cognitive processing
      is hindered by personally relevant themes of past traumatic experiences, whereas
      it may be facilitated by information related to general threat or internal body
      sensations of panic.

PMID- 9160615
TI  - Dental phobia among Saudis.
AB  - This study compares dental fear and phobias among patients attending: (1) primary
      care dental clinics, or (2) specialist dental clinics, or (3) nondental clinics.
      Of 853 patients, 539 from dental clinics and 314 from nondental clinics were
      interviewed in a structured interview. Patients from primary dental clinics and
      from specialist dental clinics did not differ. However, nondental clinic patients
      had more dental phobia and more avoidance of dental clinics. Dental clinic
      patients had more chronic dental problems than did nondental clinic attenders.
      Dental phobia was much more common among women, whose onset age was younger than
      in men, and the phobia interfered greatly with dental care. Dental phobics had
      fainted more often during dental treatment, had more chronic dental problems,
      more family history of dental phobia, and more blood and specific phobias. Most
      of the dental phobics reported dental trauma before the fear started.

PMID- 9160616
TI  - Tidal volume of respiration and "sighing" as indicators of breathing
      irregularities in panic disorder patients.

PMID- 9160617
TI  - The DSM-IV panic disorder field trial: panic attack frequency and functional
      disability.
AB  - The goal of the DSM-IV panic disorder field trial was to provide an empirical
      basis for choosing between alternate proposals (DSM-III-R and proposed DSM-IV)
      for the diagnostic threshold for panic disorder, in particular the number and
      frequency of panic attacks required for diagnosis. The two criteria sets were
      compared with respect to their ability to identify individuals whose panic
      attacks were associated with distress, impairment, or help-seeking. Subjects were
      a convenience sample screened in three geographically diverse primary care
      clinics for presence (past 6 months) or absence (lifetime) of panic attacks. Each
      underwent a clinician-administered semistructured interview which included
      assessment of panic frequency, panic-related impairment, psychiatric diagnosis,
      health services utilization, and medical illness. Self-perceived health-related
      quality of life was assessed using the Medical Outcome Study SF-36 Health Survey
      Questionnaire. Although both proposals diagnosed the same proportion of panic
      impaired individuals, they were not completely overlapping. Twenty percent of
      subjects diagnosed by each criteria set were excluded by the other. Subjects who
      had been excluded by the DSM-III-R but included by the DSM-IV proposal were those
      with fewer than 4 attacks in 4 weeks who also denied worry about the "next"
      attack. Broadening the worry criterion to include concerns about the health
      implications of attacks enabled diagnosis of this group. Subjects who met DSM-III
      R, but not the proposed DSM-IV criteria, had 4 attacks in 4 weeks but denied any
      panic related worry. Modification of the DSM-IV proposal to include a month of
      worry or "a significant change in behavior related to the attacks" allowed
      inclusion of this group in the diagnostic category. These data suggest that the
      finalized DSM-IV panic disorder criteria will diagnose a greater proportion of
      individuals whose panic attacks are associated with impairment without inflating
      the diagnostic category or significantly reducing specificity.

PMID- 9160618
TI  - Economic costs of anxiety disorders.
AB  - Anxiety disorders are estimated to affect 26.9 million individuals in the United
      States at some point during their lives. This study used the human capital
      approach to estimate the direct and indirect costs of these highly prevalent
      disorders. In 1990, costs associated with anxiety disorders were $46.6 billion,
      31.5% of total expenditures for mental illness. Less than one-quarter of costs
      associated with anxiety disorders were for direct medical treatment; over three
      quarters were attributable to lost or reduced productivity. Most of these
      indirect costs were associated with morbidity, as mortality accounted for just
      2.7% of the total. Greater availability of effective, relatively low-cost
      outpatient treatment could substantially reduce the economic and social burden of
      these common and often crippling disorders.

PMID- 9160619
TI  - Panic disorder and social phobia: effects of comorbidity on familial
      transmission.
AB  - The aim of this study was to examine effects of comorbidity of panic disorder and
      social phobia on familial transmission of each of these disorders. Rates of panic
      disorder and social phobia were compared in directly interviewed relatives of
      four proband groups: (1) panic disorder, (2) social phobia, (3) panic disorder
      and social phobia, and (4) never ill controls. Anxiety disorder probands had no
      additional lifetime anxiety disorder comorbidity. The familial pattern of the
      comorbid (panic disorder and social phobia) probands resembled that of the panic
      disorder group: an increased rate of panic disorder but not social phobia as
      compared to relatives of controls. Relatives of social phobia probands had an
      increased rate of social phobia but not panic disorder. These data indicate that
      social phobia in individuals who subsequently develop panic disorder: (1) differs
      with respect to familial transmission from social phobia which occurs without
      lifetime anxiety comorbidity; and (2) may be nonfamilial and/or causally related
      to panic disorder. Additional studies in larger epidemiologic samples are
      required to assess generalizability of these findings.

PMID- 9160620
TI  - Danger expectancies and insight in spider phobia.
AB  - Differences between phobic and normal subject perceptions of danger were
      examined. Nineteen spider-fearful subjects and a matched set of controls gave
      danger ratings before and during a spider-avoidance test. When detached from the
      phobic stimulus, spider-fearful subjects: (1) gave higher estimates of the
      probability of being bitten than did controls, (2) gave higher estimates of the
      injuries that would result from being bitten, and (3) believed their high levels
      of anticipated anxiety were more reasonable and appropriate to the demands of the
      situation than did controls. These findings are inconsistent with both the
      traditional account and Beck and Emery's (1985) more recent view that, when
      detached from the phobic situation, patients can accurately evaluate the danger
      of potential phobic encounters. The present results question the view that phobic
      individuals have complete insight into the inappropriateness of their own
      distress.

PMID- 9160621
TI  - Primate displacement activities as an ethopharmacological model of anxiety.
AB  - Using a within-subject cross-over, vehicle-controlled design, we investigated the
      acute effects of benzodiazepine receptor ligands with different mechanisms of
      action on the displacement activities (scratching, self-grooming, and body shake)
      of seven male macaques living in social groups. Our aim was to test the
      discriminative validity of displacement activities as an ethopharmacological
      model of anxiety. Subjects were given i.m. lorazepam (0.10, 0.20, 0.25 mg/ kg)
      and FG 7142 (0.1, 0.3, 1.0 mg/kg). The frequency of displacement activities was
      decreased by the anxiolytic lorazepam and increased by the anxiogenic FG 7142 in
      a dose-dependent manner. Displacement activities were apparently more sensitive
      to anxiolytic treatment than other behavior patterns indicative of an anxiety
      state (i.e., visual scanning of the social environment and fear responses
      directed to dominant males). These results suggest that primate displacement
      activities are a valid ethopharmacological model of anxiety.

PMID- 9160622
TI  - Comparison of fluvoxamine, imipramine, and placebo in the treatment of
      outpatients with panic disorder.
AB  - Fluvoxamine and imipramine were compared to placebo in an 8-week doubleblind
      randomized multicentre trial comprising of 148 outpatients between 19 and 57
      years of age (mean: 35) with a DSM-III-R diagnosis of Panic Disorder. mean daily
      dose at endpoint was: fluvoxamine, 171.4 mg; imipramine 164.7 mg. The mean number
      of panic attacks per week at baseline were 10.9, 14.4 and 6.5 for fluvoxamine,
      imipramine and placebo, respectively. The intent-to-treat analysis of the change
      from baseline (difference score) of the number of panic attacks at endpoint
      revealed: a difference of 3.3 attacks (95% CI: -0.3, 6.8) between fluvoxamine and
      placebo and a difference of 6.0 attacks (95% CI: 1.5, 10.5) between imipramine
      and placebo. Treatment was stopped prematurely in 31 (62%) on fluvoxamine, 16
      (33%) on imipramine and 29 (58%) on placebo. The number of patients withdrawing
      due to intolerance was 13 (26%) for fluvoxamine, 10 (21%) for imipramine and 4
      (8%) for placebo. The number of patients withdrawing due to lack of efficacy was
      10 (20%) for fluvoxamine, 4 (8%) for imipramine and 12 (24%) for placebo.
      Overall, this study demonstrated that fluvoxamine was not effective in the
      treatment of panic disorder but did show a strong effect for imipramine. A chance
      occurrence of significantly fewer number of panic attacks in the placebo group at
      baseline may limit the conclusions of this study.

PMID- 9160623
TI  - Ondansetron in the treatment of panic disorder.

PMID- 9160624
TI  - Theme of current journal issue: anxiety disorders across the lifespan.
AB  - The papers presented in this issue of Anxiety document various aspects of
      vulnerability to, and consequences of, anxiety disorders in subjects from
      different periods of the lifespan. Several themes are represented in one or more
      of these studies, (1) effects of anxiety disorders on quality of life, (2)
      effects on presentation and outcome of comorbid depression, and (3) the role of
      learning processes and early experiences, including abuse, attachment
      disturbances and personality disorders, in the ongoing predilection to anxiety
      disorders. We encourage clinicians and researchers to take a life course
      perspective in working with anxiety disorder patients, in order to better
      understand, prevent and treat these debilitating conditions.

PMID- 9160625
TI  - Phenomenology and severity of major depression and comorbid lifetime anxiety
      disorders in primary medical care practice.
AB  - The psychiatric history and presenting clinical characteristics of 276 depressed
      primary care patients with and without a lifetime comorbid anxiety disorder were
      studied in a randomized control trial of treatments for major depression. Our
      findings indicate that distinctive patterns of depressive symptoms and severity,
      functional impairment, comorbidity of other DSM-III-R Axis I and Axis II
      disorders, and treatment participation are associated with lifetime histories of
      panic and generalized anxiety disorder. The most consistent differences are
      evident between patients with major depression alone and those with major
      depression and a lifetime panic disorder. The latter presented with greater
      depressive severity, greater impairment in physical and psychosocial functioning,
      and were more likely to have a history of alcohol dependence, somatization
      disorder, and avoidant personality disorder. Discriminant function analysis
      indicated that 66% of depressed patients with lifetime panic disorder could be
      correctly distinguished from those without such comorbidity on the basis of the
      severity of somatic and affective symptoms but not cognitive symptoms of
      depression. Further, depressed patients with lifetime panic disorder were more
      likely to prematurely terminate both pharmacotherapy and psychotherapy during
      each treatment's acute phase. Implications for the diagnosis and treatment of
      major depression with comorbid anxiety disorder in primary care patients are
      discussed.

PMID- 9160626
TI  - Acute stress disorder, subsequent posttraumatic stress disorder and depression
      after a series of typhoons.
AB  - From August to November 1992, five typhoons struck the U.S. Pacific island
      territory of Guam. Three hundred and twenty subjects exposed to all five typhoons
      participated in a population survey measuring their acute stress symptoms and
      subsequent diagnoses of posttraumatic stress disorder (PTSD) and depression. A 23
      item scale approximating the new DSM-IV diagnosis of acute stress disorder (ASD)
      was used to classify subjects into three groups based on their symptoms one week
      after the first typhoon: (1) probable ASD, (2) an early traumatic stress response
      (ETSR) of fear, intrusion, avoidance, and arousal, without dissociation, and (3)
      no acute diagnosis. A multi-dimensional measure of PTSD and the Zung Self-Rating
      Depression Scale were used to assess PTSD and depression 8 months after the first
      storm. The point prevalence of ASD at one week was 7.2%. An additional 15% of
      subjects had ETSR. Subjects with probable ASD at one week had significantly
      increased rates of PTSD and somewhat higher rates of depression at 8 months than
      those without ASD. In contrast, subjects with ETSR at one week did not have a
      poorer outcome than those with no acute diagnosis. These findings suggest that
      ASD is prognostically important, but also indicate that all acute stress symptoms
      do not have the same discriminative value. In this study, the acute dissociative
      symptoms of emotional numbing and derealization differentiated highly symptomatic
      subjects at risk for subsequent psychopathology (ASD) from others who were highly
      symptomatic at one week, but then had a more benign, posttraumatic course (ETSR).

PMID- 9160627
TI  - Posttraumatic stress disorder, depression, alcohol use disorders and quality of
      life in adolescents.
AB  - Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder among
      adolescents. While the effects of PTSD on quality of life (QOL) have been
      systematically studied with adults, research on the consequences of PTSD with
      adolescents has been limited. Among the other psychiatric disorders often
      associated with PTSD, major depression and alcohol use disorders are prevalent
      and have their own substantial morbidities. This study was designed to examine
      and compare the effects of PTSD, major depression, and alcohol use disorders on
      quality of life during adolescence. The subjects were 540 adolescents (ages 12-18
      years old) recruited from clinical and community sources. Psychiatric disorders
      characterizing the sample included one or more of the three disorders studied (n
      = 275), other psychiatric disorders (n = 121), or no psychiatric disorders (n =
      144). Analysis of covariance was utilized to determine the individual main
      effects and relative effects sizes of the three primary disorders on QOL
      variables. PTSD showed significant adverse effects on psychological, physical,
      and social functioning. Major depression showed a similar pattern. In contrast,
      alcohol use disorders primarily affected role functioning. While PTSD, major
      depression, and alcohol use disorders all adversely influenced adolescent QOL,
      the patterns of their effects differed. Remedial treatment interventions designed
      to restore QOL for adolescents with these disorders may need to focus on
      different areas for adolescents with PTSD or major depression than for
      adolescents with alcohol use disorders.

PMID- 9160628
TI  - Childhood adversity, attachment and personality styles as predictors of anxiety
      among elderly caregivers.
AB  - The purpose of this study was to examine the ways in which childhood adversity,
      attachment and personality styles influenced the likelihood of having an anxiety
      disorder among aged caregivers for terminally ill spouses. We also sought to
      determine how childhood adversity and attachment/personality styles jointly
      influenced the likelihood of developing an anxiety disorder among aged
      caregivers. Data were derived from semistructured interviews with 50 spouses
      (aged 60 and above) of terminally ill patients. The Childhood Experience of Care
      and Abuse (CECA) record provided retrospective, behaviorally based information on
      childhood adversity. Measures of attachment and personality styles were obtained
      from self-report questionnaires, and the Structured Clinical Interview for the
      DSM-III-R (SCID) was used to determine diagnoses for anxiety disorders. Logistic
      regression models estimated the effects of childhood adversity,
      attachment/personality disturbances, and the interaction between the two on the
      likelihood of having an anxiety disorder. Results indicated that childhood
      adversity and paranoid, histrionic and self-defeating styles all directly
      increase the odds of having an anxiety disorder as an elderly spousal caregiver.
      In addition, childhood adversity in conjunction with borderline, antisocial and
      excessively dependent styles increased the likelihood of having an anxiety
      disorder. The results indicate the need to investigate further the interaction
      between childhood experiences and current attachment/personality styles in their
      effects on the development of anxiety disorders.

PMID- 9160630
TI  - Origins of specific fears: a comparison of associative and nonassociative
      accounts.

PMID- 9160629
TI  - Comorbid anxiety disorders in late-life depression.
AB  - We examined the prevalence and correlates of comorbid anxiety disorders in two
      groups of older depressed patients assessed at the University of Pittsburgh. A
      total of 336 older outpatients and inpatients with major depression were
      comprehensively evaluated with several instruments including the Hamilton
      Depression Rating Scale, and either the SADS-L or the SCID for DSM-III-R. These
      patients presented with major depression, associated with a wide range of
      functional, cognitive, and medical impairment. One-third to one-half of them also
      presented with severe symptomatic anxiety. However, only a small proportion (less
      than 5%) met diagnostic criteria for lifetime or current panic, obsessive
      compulsive, or phobic disorders. At baseline, lifetime comorbid anxiety disorders
      were associated with a higher rate of alcoholism and higher symptomatic anxiety.
      Lifetime comorbid anxiety disorders did not affect the rate of response of
      depression, but they were associated with a higher use of benzodiazepines and a
      50% increase in the time outpatients needed to respond. These findings suggest
      that, even in psychiatric patients with major depression, the lifetime prevalence
      of anxiety disorders is lower in late life, but that it has important clinical
      and therapeutic implications.

PMID- 9160632
TI  - What looks good and is good for you? The Journal Depression and Anxiety.

PMID- 9160631
TI  - Temperamental variables in PTSD patients.

PMID- 9160633
TI  - On the need for standardization in panic disorder treatment research: survey of
      the literature, 1980-1992.
AB  - A retrospective literature survey (1980-1992) was conducted to chronicle the
      development of panic disorder treatment research. Based on a National Institute
      of Mental Health conference on assessment standardization in this area (Shear and
      Maser, 1994), the results and implications of the survey are presented in terms
      of eight domains of measurement recommended as essential for high quality
      research.

PMID- 9160634
TI  - Non-random associations between fears, beliefs and behaviors among panic
      patients.
AB  - Self-report questionnaires have been used to compare panic patients' fears,
      anxious thoughts and behaviors with those of a group of controls. Individual
      items revealed significant differences between groups in all three areas: factor
      analysis revealed group differences in the pattern of intraquestionnaire
      associations between items. Correlational analysis of factor scores revealed
      significant group differences in the pattern of interquestionnaire associations.
      These findings only partly support a formulation of panic based upon
      "catastrophic interpretations." On the other hand, they do provide evidence of
      cognitive rigidity among panic patients which can be interpreted as evidence of
      impaired effortful processing when anxious.

PMID- 9160635
TI  - Cognitive differences between anxious, normal, and ADHD children on a dichotic
      listening task.
AB  - To compare the performance of children with anxiety disorders with that of
      children with attention-deficit hyperactivity disorder (ADHD) and normal controls
      in the processing of emotional information. A total of 57 children ages 8 to 11
      years (18 anxious, 20 ADHD, 19 normal control) were administered a dichotic
      listening task for the detection of words and emotions. Comparisons of overall
      performance, false alarms, and a sensitivity index (which took false alarms into
      account) were done using repeated measures analyses of variance. Anxious children
      made fewer false alarms for emotion targets compared to both ADHD children and
      normal controls, and fewer false alarms for words compared to normal controls.
      When controlling for false alarms, their performance exceeded that of both ADHD
      children and normal controls. There were no group differences in correct
      responses. Performance on a dichotic listening task differentiates anxious, ADHD,
      and normal children, particularly when listening for emotional targets. Further
      studies using this task may therefore elucidate differences in the processing of
      words and emotions between these three groups of children.

PMID- 9160636
TI  - Personality disorder symptomatology among Vietnam veterans with combat-related
      PTSD.
AB  - This research examined self-report personality profiles of 42 Vietnam veterans
      with combat-related posttraumatic stress disorder (PTSD) evaluated at an
      outpatient Veteran's Administration hospital PTSD clinic. Assessment was via the
      Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental
      Disorders (3rd ed., rev; DSM-III-R) Personality Disorders-II (SCID-II) self
      report. Self-reported personality disorder symptomatology of PTSD patients was
      contrasted with that of 51 outpatients with a primary diagnosis of an anxiety
      disorder other than PTSD and with 16 patients with a primary diagnosis of major
      depressive disorder (MDD). Symptomatology from each of the 11 DSM-III-R
      categories and from the three personality disorder "clusters" was calculated in
      terms of percentage of possible traits endorsed, thus creating personality
      "profiles" for the three groups. PTSD veterans endorsed more traits overall than
      did both the mixed anxiety and MDD groups, particularly on the Cluster A,
      avoidant, and borderline scales. Results suggest a PTSD-related personality
      profile characterized by emotional lability/poor anger control,
      paranoia/suspiciousness, identity disturbance/confusion, social
      withdrawal/avoidance, and feelings of emptiness and boredom.

PMID- 9160637
TI  - Ambulatory monitoring of respiration in anxiety.
AB  - An ambulatory monitor, body suit, and calibration procedure were developed to
      compare the respiration of seven patients with panic disorder and twelve normal
      volunteers. Subjects wore a body suit with Respitrace bands, connected to a
      portable respiratory monitor for a period of 24 hours. Breath by breath values
      for respiratory rate and tidal volume were computed every two minutes. There was
      a significant difference between patients and controls in their patterns of
      minute ventilation during sleep. Tidal volume, rather that respiratory rate
      increases characterized the periods of anxiety and limited symptom attacks.

PMID- 9160638
TI  - Just how common are common fears?

PMID- 9160639
TI  - Ballatrophobia: when clowns aren't funny.

PMID- 9160640
TI  - Venlafaxine: a novel antidepressant that has a dual mechanism of action.
AB  - Major depressive disorder (MDD) is a common affective disorder that is associated
      with a range of psychiatric disturbances. The pathophysiology of MDD is commonly
      believed to involve the reduced availability of the monoamines, serotonin (5-HT)
      and norepinephrine (NE), the enhancement of which is also believed to mediate, at
      least in part, the therapeutic effects of antidepressants. The first-generation
      antidepressants, the tricyclic antidepressants (TCAs), provide considerable
      efficacy but have several limitations, including (1) delayed onset of action, (2)
      intolerable or distressing side effects, (3) low therapeutic index, and (4) a
      significant proportion of nonresponders. The second-generation antidepressants,
      the selective-serotonin-reuptake inhibitors (SSRIs), mitigate some of the side
      effects associated with the TCAs by selectively inhibiting the reuptake of 5-HT.
      Venlafaxine is a new antidepressant that blocks reuptake of both 5-HT and NE. It,
      like the SSRIs, has a relatively benign side-effect profile. In addition, it may
      exert a rapid onset of action, and it appears to be particularly effective in
      moderate-to-severe depression and in patients who have treatment-refractory
      depression.

PMID- 9160641
TI  - Depression in patients with coronary artery disease.
AB  - Depression is more prevalent in patients with coronary artery disease (CAD) than
      in the general elderly population. Although CAD patients with depression have
      higher mortality rates, depression is often not recognized and treated in these
      patients. We administered structured psychiatric diagnostic interviews to 99
      inpatients with CAD and diagnosed 23% with a major depressive episode (MDE) by
      DSM-IV criteria. Severity of medical illness and family history of
      psychopathology were indicators for increased risk for MDE. These findings may
      facilitate the recognition of CAD patients at greater risk for MDE.

PMID- 9160642
TI  - Six month follow-up of early-onset chronic depression.
AB  - BACKGROUND: This study sought to characterize the morbidity and treatment
      behavior of 49 patients with early-onset chronic depression, 6 months after
      terminating treatment at a university-based psychopharmacology research clinic.
      METHOD: Patients with and without early-onset chronic depression were selected to
      participate in a naturalistic follow-up study. Assessments were conducted blind
      to patients' histories. Patients' depressive symptoms, psychosocial functioning,
      and post-discharge treatment histories were assessed. RESULTS: After termination,
      the mean length of recovery for the sample was 3.6 months. When they left the
      clinic, 78% (38/49) were euthymic. At follow-up, 37% (14/38) of these had
      relapsed; while 45% (17/38) remained in remission for 6 months. During the follow
      up period, 47% of the patients were on antidepressants. Sixty-three percent of
      the patients who relapsed, or were depressed when they left the clinic, did not
      enter treatment, 50% of whom cited insufficient resources as the primary reason
      for not receiving care. CONCLUSIONS: After leaving a depression research clinic,
      a substantial portion of patients with early-onset chronic depression remained
      recovered during a 6-month period, but financial impediments prevented a majority
      of those who did poorly from entering treatment.

PMID- 9160643
TI  - Depressive symptoms: associations with health perceptions and health behaviors.
AB  - The association of depressive symptoms with health behaviors and perceptions was
      determined for 876 patients seeing family physicians. Correlational analyses
      revealed stress, pain, and overall health status were moderately related to
      depression for males and females. Smoking was positively related to depressive
      symptoms in women (r = .19, P < 0.01), and drinking was inversely related to
      depressive symptoms in men (r = -.16, P < .01). Multiple regression analyses
      indicated stress, poor health, smoking, and drinking were significant predictors
      of depressive symptoms in women; stress, poor health, and drinking were
      significant in men. Health perceptions appear to be better predictors of
      depressive symptoms than reported health behaviors.

PMID- 9160644
TI  - Lack of association between thyroid and pineal responses to antidepressant
      treatment.
AB  - With antidepressant treatment for major depression there are decreases in thyroid
      hormone levels and increases in pineal function. We have conducted a study to
      examine whether there is a relationship between pineal and thyroid hormone
      measures as well as between hormone measures and response to treatment in
      patients treated with desipramine. Measures of thyroid activity included
      thyroxine, triiodothyronine, T3 resin uptake, and TSH. Pineal function was
      determined by measurement of 6-suphatoxymelatonin in three consecutive 8 hour
      pools. Hormone measures as well as Hamilton depression scores were obtained prior
      to treatment and at the end of 5 weeks of treatment. As in previous studies,
      thyroid measures decreased, pineal activity increased, and Hamilton scores
      decreased significantly with treatment. No correlations were found between these
      measures, suggesting that if there is a relationship between them it is not a
      direct one.

PMID- 9160645
TI  - Do patients use marijuana as an antidepressant?
AB  - Several lines of evidence suggest that cannabis may have antidepressant effects.
      However, methodologic limitations in available studies make the results difficult
      to interpret. We review this literature and present five cases in which the
      evidence seems particularly clear that marijuana produced a direct antidepressant
      effect. If true, these observations argue that many patients may use marijuana to
      "self-treat" depressive symptoms.

PMID- 9160646
TI  - Effects of self-generated sad mood on regional cerebral activity: a PET study in
      normal subjects.
AB  - This study investigated the cerebral regions modulated by self-generated sad mood
      in normal subjects. Eleven healthy men experienced a temporary sad mood by
      recalling sad personal memories. Two control states were used for comparison: a
      resting condition, and a condition involving the recall of affectively neutral
      personal events. Regional cerebral blood flow (rCBF) images were obtained using
      [15O]-H2O Positron Emission Tomography. A statistical comparison of the images
      during negative mood and neutral recall conditions revealed that sad mood was
      associated with a decrease in rCBF in the left dorsolateral prefrontal, left
      medial prefrontal, and left temporal cortex; no increase in activity was noted in
      this comparison. Our results are consistent with the noted left prefrontal
      decrease in metabolism found in depressed patients through a variety of
      methodologies; however, our results contrast with findings of increased left or
      bilateral prefrontal activity in transient induced negative mood states reported
      for women (George et al., 1995, Am J Psychiatry 152:341-341) and for mixed-gender
      (Pardo et al., 1993, Am J Psychiatry 150:713-719) subject groups. The study
      brings to light a number of methodological issues, including the crucial
      importance of the baseline condition used for the isolation of the emotional
      components of a given task.

PMID- 9160647
TI  - An empirical study of the psychodynamics of suicide: a preliminary report.
AB  - Preliminary results from a study of psychodynamic constructs are presented based
      on data from inpatients following a suicide attempt. The study examines the
      association between four psychodynamic constructs, severity of suicidal intent,
      and severity of depressive symptomatology in a sample of hospitalized suicide
      attempters. Higher levels of suicidal intent were associated with less
      differentiated self and object representations and less emotional investment in
      relationships. More severe depressive symptoms in suicide attempters were
      correlated with more self-targeted anger, less eternally directed anger, higher
      levels of shame and guilt, more affectively negative views of relationships,
      greater use of maladaptive and self-sacrificing defenses, and more impaired
      reality testing. These findings offer some preliminary empirical support for the
      validity of psychodynamic theories of suicidal behavior.

PMID- 9160648
TI  - Rapid cycling triggered by pindolol augmentation of paroxetine, but not with
      desipramine.
AB  - A treatment-resistant depressed patient developed bipolar rapid cycling in
      response to pindolol augmentation of paroxetine, after failing to respond in any
      fashion to pindolol added to desipramine. The rapid cycling initially faded, but
      recurred after the pindolol dose was increased (in combination with paroxetine)
      in an attempt to treat a relapse into depression. Her differential development of
      rapid cycling with pindolol in combination with the SSRI is in keeping with the
      theory that pindolol augmentation operates via a serotonergic mechanism.

PMID- 9160649
TI  - Trimipramine and imipramine exert different effects on the sleep EEG and on
      nocturnal hormone secretion during treatment of major depression.
AB  - In a 4-week double-blind clinical trial we compared the effects of the tricyclic
      antidepressants trimipramine and imipramine on the sleep EEG and on nocturnal
      bormone secretion in 20 male inpatients with major depression. Both treatments
      produced rapid significant clinical improvement in depression without severe
      adverse effects. However, the two drugs had markedly different neurobiologic
      profiles. Trimipramine enhanced rapid eye movement (REM) sleep and slow wave
      sleep, whereas imipramine suppressed REM sleep and showed no effect on slow wave
      sleep. Total sleep time and the sleep efficiency index increased under
      trimipramine but not under imipramine. Nocturnal cortisol secretion decreased
      with trimipramine but remained unchanged with imipramine. In contrast to
      imipramine, trimipramine induced an increase in prolactin secretion compatible
      with its known antagonism at dopamine (D2) receptors. Imipramine induced a
      decrease in growth hormone secretion during the first half of the night. Neither
      of the drugs induced significant changes in plasma testosterone concentration. We
      conclude that trimipramine is an antidepressant with sleep-improving qualities
      that possibly acts through inhibition of hypothalamic-pituitary-adrenocortical
      system activity by a yet unknown mechanism.

PMID- 9160650
TI  - Nuclear magnetic resonance spectroscopy: new insights into the pathophysiology of
      mood disorders.
AB  - Magnetic Resonance Spectroscopy (MRS) is a novel non-invasive approach for
      investigation of in vivo brain neurochemistry. In this paper, we review the
      initial studies conducted in mood disorders. 31P MRS studies have suggested
      membrane phospholipid and energy metabolism abnormalities in the frontal and
      temporal lobes of bipolar patients. 1H MRS studies have pointed to increase in
      choline resonance in the basal ganglia of patients with unipolar and bipolar
      disorders. Mood disorders are not associated with reductions in N-acetyl
      aspartate, unlike schizophrenia and other neuropsychiatric disorders. Both 31P
      and 1H MRS have begun to be used to investigate the mechanisms of action of ECT.
      19F and 7Li MRS offer therapeutically relevant new tools for
      psychopharmacological investigation, allowing the determination of brain
      concentrations of psychotropic drugs. Measurement of in vivo brain lithium
      concentrations may have clinical relevance. While several methodological
      limitations persist, the noninvasiveness and the unique neurochemical insights
      provided by MRS offer an excellent opportunity for in vivo investigation of the
      neurobiology of mood disorders.

PMID- 9160651
TI  - Factor analysis of the Montgomery-Asberg Depression Rating Scale.
AB  - A maximum likelihood factor analysis with Promax rotation was performed on the
      Montgomery-Asberg Depression Rating Scale for 340 adult inpatients in an
      Affective Disorders Program. Four factors were identified and labeled cognitive
      pessimism, affective, cognitive-anxiety, and vegetative. Recommendations were
      offered for the research and clinical use of the factor scores.

PMID- 9160652
TI  - Cognitive therapy versus fluoxetine in the treatment of dysthymic disorder.
AB  - We studied the effects of a fixed dose of fluoxetine (20 mg) or cognitive
      psychotherapy in a 16 week trial of patients with dysthymic disorder. More
      patients assigned to fluoxetine dropped out of the 16 week treatment (33%) than
      those assigned to cognitive therapy (9%), but this difference did not attain
      statistical significance. Both treatments showed improvement over baseline
      conditions at 8 weeks and further improvement at 16 weeks. There were no
      statistically significant group differences in treatment response. No follow-up
      data were collected so the enduring effects of the treatments are unknown. An
      optimal treatment for dysthymic disorder may be combined psychotherapy and
      pharmacotherapy for a longer period of time.

PMID- 9160653
TI  - Eosinophils and IgE receptors: a continuing controversy.

PMID- 9160654
TI  - CD antigens 1996.

PMID- 9160655
TI  - Granules of the human neutrophilic polymorphonuclear leukocyte.

PMID- 9160656
TI  - Expression of the human immunodeficiency virus type-1 coreceptors CXCR-4 (fusin,
      LESTR) and CKR-5 in CD34+ hematopoietic progenitor cells.
AB  - CD34+ hematopoietic progenitor cells were assessed for mRNA expression of the
      human immunodeficiency virus type-1 (HIV-1) coreceptors CXCR-4, also termed fusin
      or LESTR, and CKR-5, also called CC-CKR-5 or CCR-5. The CD34+ cells were obtained
      from leukapheresis products of 17 patients after granulocyte colony-stimulating
      factor-supported cytotoxic chemotherapy. Using a two-step enrichment procedure
      including immunomagnetic bead separation and fluorescence-activated cell sorting,
      the CD34+ cells had a median purity of 99.8%. Assessing 9 CD34+ cell samples by
      polymerase chain reaction after reverse transcription (RT-PCR), CXCR-4 mRNA was
      found in all samples, whereas CKR-5 mRNA was only present in 3 samples, even
      though a nested PCR was used. Eight additional CD34+ cell samples were sorted
      according to CD4 expression. Based on a three-color immunofluorescence analysis,
      the mean relative fluorescence intensity of HLA-DR was smaller on CD34+/CD4+
      cells in comparison with CD34+/ CD4- cells. CXCR-4 mRNA was found in 5 of 8
      CD34+/CD4+ samples and in 7 of 8 CD34+/CD4- samples, whereas CKR-5 mRNA was
      detected in 2 CD34+/CD4+ samples and in 1 CD34+/CD4- cell sample. Looking at the
      total number of CD34+ cell samples examined, the proportion of specimens
      containing CXCR-4 mRNA was 84% in comparison with 24% of specimens positive for
      CKR-5 mRNA. These data suggest that CD34+/CD4+ hematopoietic progenitor cells,
      including true stem cell candidates, could be susceptible to HIV-1 infection.
      Considering the relatively low incidence of CD34+ cell samples containing CKR-5
      mRNA, CD34+/CD4+ cells appear to be particularly prone for HIV-1 infection via
      the CXCR-4 coreceptor. Because this chemokine receptor allows T-cell-tropic HIV-1
      strains to infect cells, CD34+ cells expressing CD4 and CXCR-4 might be infected
      by HIV-1 during later stages of the disease, following a viral phenotype switch
      from macrophage- to T-cell-tropic HIV-1 strains.

PMID- 9160658
TI  - Chronic myelomonocytic leukemia in childhood: a retrospective analysis of 110
      cases. European Working Group on Myelodysplastic Syndromes in Childhood (EWOG
      MDS)
AB  - Chronic myelomonocytic leukemia (CMML) is a rare hematopoietic malignancy of
      childhood. To define the clinical and hematologic characteristics of the disease,
      we performed a retrospective analysis of 110 children given the diagnosis CMML
      irrespective of karyotype. Median age at diagnosis was 1.8 years.
      Neurofibromatosis type 1 was known in 14% and other clinical abnormalities in 7%
      of the children. At presentation, the medium white blood count was 35 x 10(9)/L,
      with a median monocyte count of 7 x 10(9)/L. Karyotypic abnormalities in bone
      marrow cells were noted in 36% of the patients, whereas 26% of the children had
      monosomy 7. Children with monosomy 7 did not differ from those with normal
      karyotype with respect to their clinical presentation. However, they did display
      some characteristic hematologic features. Of 110 children, 38 received an
      allogeneic bone marrow transplant (BMT). The probability of survival at 10 years
      was 0.39 (standard error [SE] = 0.10) for the BMT group and 0.06 (SE = 0.4) for
      the 72 patients of the non-BMT group. Platelet count, age, and hemoglobin F at
      diagnosis were the main predicting factors for the length of survival in the non
      BMT group. There is a strong need for a broad agreement on nomenclature in
      children with myelodysplastic syndromes (MDS). We propose here to use the French
      American-British classification for MDS in childhood.

PMID- 9160657
TI  - A multicenter controlled, randomized, open trial of interferon alpha2b treatment
      of anti-human immunodeficiency virus-negative hemophilic patients with chronic
      hepatitis C. Hepatitis Study Group of the Association of Italian Hemophilia
      Centers.
AB  - There is limited information about the long-term efficacy of prolonged therapy
      (more than 6 months) with interferon alpha in hemophilic patients with chronic
      hepatitis C who are not coinfected with the human immunodeficiency virus (HIV-1).
      One hundred and seven hemophiliacs were randomly assigned to 3 million U of
      interferon alpha2b three times weekly for 12 months or no therapy. The patients
      were followed up for at least 12 months posttreatment. Response was assessed by
      both serial alanine aminotransferase (ALT) levels and hepatitis C virus (HCV)-RNA
      measured by reverse transcribed polymerase chain reaction (RT-PCR) method. Before
      treatment, serum levels of HCV-RNA were measured quantitatively by second
      generation branched-DNA assay and the HCV genotype was determined by RT-PCR.
      Serum HGV-RNA, a marker of infection with the hepatitis G virus, was also
      measured by RT-PCR. Normalization of ALT was sustained and serum HCV-RNA was
      cleared in 6 of 45 treated patients, compared with none of the 50 untreated
      controls (13% v 0% P < .01). Low pretreatment viremia was the only feature that
      was associated with an increased likelihood of sustained response (P < .01). This
      study shows that multitransfused hemophiliacs with chronic hepatitis C not
      coinfected with HIV-1 respond at low rates to prolonged interferon therapy.

PMID- 9160659
TI  - Thrombopoietin does not induce lineage-restricted commitment of Mpl-R expressing
      pluripotent progenitors but permits their complete erythroid and megakaryocytic
      differentiation.
AB  - In this study, we examined the in vitro and in vivo effects of forced expression
      of Mpl-R (the thrombopoietin receptor) on the progeny of murine hematopoietic
      stem cells. Bone marrow cells from 5-FU-treated mice were transduced with
      retroviral vectors containing the human Mpl-R cDNA, or the neomycine gene as a
      control. After 7 days cocultivation on virus-producer cells, GpE86-Mpl-R or Gp86
      Neo, the types of hematopoietic progenitor cells responding to thrombopoietin
      (TPO) were studied by clonogenic assays. Mpl-R-infected cells gave rise to CFU
      GEMM, BFU-E, CFU-MK, but not CFU-GM while Neo-infected cells produced only
      megakaryocytic colonies. In addition, when nonadherent cells from GpE86-Mpl-R
      cocultures were grown with TPO as the only stimulus for 7 days, a marked
      expansion of CFU-GEMM, BFU-E, and CFU-MK was observed, while no change in CFU-GM
      number was seen. Erythroid and megakaryocytic maturation occurred in the presence
      of TPO while a block in granulocytic differentiation was observed at the
      myeloblast stage. The direct effects of TPO on Mpl-R-transduced progenitor cells
      were demonstrated by single cell cloning experiments. To analyze the effects of
      the constitutive expression of Mpl-R on the determination of multipotent
      progenitors (CFU-S) and long-term repopulating stem cells, Mpl-R- or Neo-infected
      cells were injected into lethally irradiated recipient mice. No difference was
      seen in (1) the number of committed progenitor cells contained in individual CFU
      S12 whether colonies arose from noninfected or Mpl-R-infected CFU-S; (2) the mean
      numbers of progenitor cells per leg or spleen of mice reconstituted with Mpl-R-
      or Neo-infected cells, 1 or 7 months after the graft; and (3) the blood
      parameters of the two groups of animals, with the exception of a 50% reduction in
      circulating platelet counts after 7 months in mice repopulated with Mpl-R
      infected bone marrow cells. These results indicate that retrovirus-mediated
      expression of Mpl-R in murine stem cells does not modify their ability to
      reconstitute all myeloid lineages of differentiation and does not result in a
      preferential commitment toward the megakaryocytic lineage.

PMID- 9160661
TI  - Fas-mediated apoptosis of the hematopoietic progenitor cells in mice infected
      with murine cytomegalovirus.
AB  - The effects of cytomegalovirus (CMV) infection on hematopoietic progenitor cells
      in vivo were investigated to elucidate the pathogenesis of CMV-induced
      myelosuppression. BALB/c mice were inoculated with 0.2LD50 of murine CMV (MCMV).
      Lineage marker negative, c-kit positive (Lin-c-kit+) and Lin-CD34+ cells, which
      are both phenotypically defined as hematopoietic progenitor cells, showed a
      significant reduction in number on day 3 postinfection (pi). Moreover, the
      reduction in the number of day-14 colony-forming units-spleen (CFU-S), another
      indicator to identify hematopoietic progenitor cells, was noted on day 3 pi. To
      clarify the mechanism of such depletion, we examined the cells undergoing
      apoptosis in the Lin- populations and found a 15-fold increase in the apoptosis
      induction of these cells. Furthermore, an increase in the expression level of
      Fas, which mediates apoptosis, was observed in such Lin-c-kit+ and Lin-Sca-1+
      cells on day 3 pi. In vitro treatment with the anti-Fas antibody accelerated the
      apoptosis in Lin- cells, but not in the uninfected control cells, thus indicating
      that the upregulated Fas on Lin- cells is directly related to the acceleration of
      apoptosis found in these cells in vivo. These results suggest that MCMV infection
      reduces the number of hematopoietic progenitor cells in bone marrow at least in
      part due to Fas-mediated apoptosis, and this phenomenon is thus considered to
      contribute to CMV-induced myelosuppression.

PMID- 9160660
TI  - Individual CD34+CD38lowCD19-CD10- progenitor cells from human cord blood generate
      B lymphocytes and granulocytes.
AB  - Identification of human hematopoietic stem cells and analysis of molecular
      mechanisms regulating their function require biological assays that permit
      differentiation in all hematopoietic lineages simultaneously. In this study, we
      established conditions that permit the joint expression of the B-lymphoid and
      myeloid potential from cord blood-derived CD34+CD38lowCD19-/CD10- primitive
      progenitors that lack B-specific markers and transcripts. When cocultured during
      6 weeks with the murine stromal cells MS-5 in the absence of exogenous human
      cytokines, CD34+CD38low-CD19-CD10- cells generated a high number of CD19+ B
      cells. Virtually all of these cells expressed a CD34-CD10+- CD19+cIgM- phenotype
      of late pro-B cells and transcripts of Pax-5, lambda-like, and mu chain were
      detected. We further show that 7% of CD34+CD38lowCD19- cells from cord blood,
      when grown individually with MS-5 cells, generated both CD19+ and CD11b+ cells
      after 6 weeks. Efficient B-cell differentiation was also observed in vivo after
      transplantation of human cord blood-derived unfractionated mononuclear cells or
      CD34+CD19+CD10- cells into immune-deficient mice. In contrast to the in vitro
      situation, all stages of B-cell differentiation were observed in vivo, including
      pro-B, pre-B, and sIgM+ B cells. Interestingly, human progenitors with the
      ability to differentiate along both B-lymphoid and granulocytic pathways were
      also detected among human CD34+CD38low cells in the marrow of chimeric mice 6 to
      7 weeks after transplantation. Both in vitro and in vivo systems will offer an
      invaluable tool to further identify the lymphoid and myeloid potentialities of
      primitive progenitor cells isolated from fetal as well as adult human
      hematopoietic tissues and characterize stromal-derived signals that regulate
      their function.

PMID- 9160662
TI  - Polycythemia vera. V. Enhanced proliferation and phosphorylation due to vanadate
      are diminished in polycythemia vera erythroid progenitor cells: a possible defect
      of phosphatase activity in polycythemia vera.
AB  - Erythropoietin (EP) and stem cell factor (SCF) are essential growth factors for
      erythroid progenitor cell proliferation and differentiation in serum-free
      culture. It has been previously shown that burst-forming units-erythroid and
      colony-forming units-erythroid from patients with polycythemia vera (PV) have
      enhanced sensitivity to EP and SCF compared with normal erythroid progenitors,
      but little is known about the mechanism for this difference. In the present
      investigation, the effect of EP and SCF on protein tyrosine phosphorylation in
      day-8 normal and PV erythroid colony-forming cells, which give rise to colonies
      of 2-49 hemoglobinized cells, was studied. EP rapidly induced tyrosine
      phosphorylation of the EP receptor, whereas the most prominent phosphorylated
      protein induced by SCF was identified as the SCF receptor. No additional
      phosphorylated proteins were evident when PV cells were compared with normal
      cells. Culture of normal erythroid progenitors with orthovanadate, an inhibitor
      of protein tyrosine phosphatases, resulted in an increased number of erythroid
      colonies and enhanced protein tyrosine phosphorylation. However, in contrast,
      little enhancement was evident with PV cells. These results indicate that,
      although vanadate may be acting in normal erythroid progenitors as a phosphatase
      inhibitor that potentiates the kinase activity induced by SCF and EP, this
      function is diminished in PV cells. Because erythropoiesis is regulated by a
      balance between protein tyrosine kinase activity and protein tyrosine phosphatase
      activity, PV patients may have an abnormal phosphatase activity allowing
      increased cell proliferation.

PMID- 9160663
TI  - Macrophage inflammatory protein-1alpha and interferon-inducible protein 10
      inhibit synergistically induced growth factor stimulation of MAP kinase activity
      and suppress phosphorylation of eukaryotic initiation factor 4E and 4E binding
      protein 1.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) and Steel factor (SLF)
      synergistically stimulate Raf-1 kinase activity, protein synthesis, and
      proliferation in hematopoietic MO7e cells; synergistic action of these factors is
      blocked by the suppressive chemokines macrophage inflammatory protein-1alpha (MIP
      1alpha) and interferon-inducible protein 10 (IP-10; Aronica et al, J Biol Chem
      270:21998, 1995). We assessed the potential for both stimulatory and inhibitory
      factors to act through the MAP kinase signaling pathway by studying the effects
      of growth factors and chemokines on MAP kinase activation. Also, because
      activation of kinase signaling pathways and stimulation of protein synthesis by
      peptide growth factors are associated with increased phosphorylation of
      eukaryotic initiation factor 4E (elF-4E) and the translational repressor 4E
      binding protein 1 (4E-BP1) in some target cells, we investigated whether growth
      factor treatment could alter eIF-4E or 4E-BP1 phosphorylation state in MO7e
      cells. We report that treatment of MO7e cells with GM-CSF and SLF stimulated
      significant, greater-than-additive increases in MAP kinase activity and the
      phosphorylation of both eIF-4E and 4E-BP1. Increased 4E-BP1 phosphorylation
      correlated with a decrease in the association of 4E-BP1 with eIF-4E. Growth
      factor-induced phosphorylation of 4E-BP1 and dissociation of 4E-BP1 from eIF-4E
      was blocked in cells treated with rapamycin, wortmannin, or PD098059. Treatment
      of cells with IP-10 or MIP-1alpha blocked the stimulatory effects of GM-CSF and
      SLF, resulting in suppression of MAP kinase activity, eIF-4E and 4E-BP1
      phosphorylation, and eIF-4E/4E-BP1 dissociation. Our results suggest that GM-CSF
      and SLF exert part of their combined growth-promoting effects on MO7e cells
      through activation of MAP kinase and enhancement of eIF-4E and 4E-BP1
      phosphorylation and dissociation and that suppression of growth factor-induced
      protein synthesis by MIP-1alpha and IP-10 involves translational repression at
      the level of eIF-4E.

PMID- 9160664
TI  - Phenotypic and functional changes induced at the clonal level in hematopoietic
      stem cells after 5-fluorouracil treatment.
AB  - A significant fraction of hematopoietic stem cells (HSCs) have been shown to be
      resistant to the effects of cytotoxic agents such as 5-fluorouracil (5-FU), which
      is thought to eliminate many of the rapidly dividing, more committed progenitors
      in the bone marrow and to provide a relatively enriched population of the most
      primitive hematopoietic progenitor cells. Although differences between 5-FU
      enriched progenitor populations and those from normal bone marrow have been
      described, it remained unclear if these differences reflected characteristics of
      the most primitive stem cells that were revealed by 5-FU, or if there were
      changes in the stem-cell population itself. Here, we have examined some of the
      properties of the stem cells in the bone marrow before and after 5-FU treatment
      and have defined several activation-related changes in the stem-cell population.
      We found that long-term reconstituting stem cells decrease their expression of
      the growth factor receptor c-kit by 10-fold and increase their expression of the
      integrin Mac-1 (CD11b). These changes begin as early as 24 hours after 5-FU
      treatment and are most pronounced within 2 to 3 days. This activated phenotype of
      HSCs isolated from 5-FU-treated mice is similar to the phenotype of stem cells
      found in the fetal liver and to the phenotype of transiently repopulating
      progenitors in normal bone marrow. We found that cell cycle is induced
      concomitantly with these physical changes, and within 2 days as many as 29% of
      the stem-cell population is in the S/G2/M phases of the cell cycle. Furthermore,
      when examined at a clonal level, we found that 5-FU did not appear to eliminate
      many of the transient, multipotent progenitors from the bone marrow that were
      found to be copurified with long-term repopulating, activated stem cells. These
      results demonstrate the sensitivity of the hematopoietic system to changes in its
      homeostasis and correlate the expression of several important surface molecules
      with the activation state of HSCs.

PMID- 9160665
TI  - Involvement of retinoic acid receptor-alpha-mediated signaling pathway in
      induction of CD38 cell-surface antigen.
AB  - Human leukocyte antigen CD38, a 45-kD single-chain, transmembrane glycoprotein,
      is a bifunctional ectoenzyme that participates in signal transduction pathways
      involved in the regulation of cell growth and differentiation. In this study, we
      demonstrate the nature of retinoid receptors involved in retinoic acid-induced
      expression of CD38 protein in the human myeloblastic leukemia cell line HL-60. We
      used a variant HL-60 cell line, HL-60R, in which retinoid receptor function has
      been abrogated by a trans-dominant negative mutation. We introduced the normal
      retinoic acid receptors (RAR)-alpha, -beta, and -gamma or retinoid X receptor
      (RXR)-alpha into HL-60R cells by retroviral vector-mediated gene transfer. Based
      on experiments using these cell lines and receptor-specific synthetic retinoids
      that preferentially bind to one of the RARs or RXRs, we conclude that RAR-alpha
      is involved in retinoid-induced CD38 expression in HL-60 cells. Further evidence
      included our demonstration that blocking of RAR-alpha with the antagonist Ro 41
      5253 completely suppressed the retinoid-induced expression of CD38 mRNA
      transcript and the production of CD38 protein in HL-60 cells. Various tissues
      from transgenic mice that expressed an antisense construct of RAR-alpha lacked or
      produced very low levels of CD38. As expected, the tissues from transgenic mice
      contained 50% to 80% reduced levels of RAR-alpha. These results suggest that
      regulation of CD38 expression, both in vitro and in vivo, is under the direct
      control of RAR-alpha retinoid receptors.

PMID- 9160666
TI  - Implication of a new molecule IK in CD34+ hematopoietic progenitor cell
      proliferation and differentiation.
AB  - HLA-DR is one of the markers associated with hematopoietic cell differentiation,
      since expression of this molecule is modulated throughout hematopoiesis. We have
      previously described and cloned the gene encoding factor IK, which inhibits both
      interferon gamma (IFN-gamma)-induced and constitutive HLA-DR expression. The
      current study demonstrates that IK gene transcripts are present in CD34+ cells
      purified from human umbilical cord blood. IK expression increased and was
      therefore inversely correlated with the gradual loss of HLA-DR during growth
      factor-induced CD34+ cell proliferation and differentiation. To study the
      possible role of IK in hematopoiesis, antisense probes were used. IK expression
      was specifically inhibited by an antisense oligodeoxynucleotide containing two
      phosphorothioate internucleotide linkages at each of the 3' and 5' ends and
      corresponding to the initiation site of IK mRNA. A control oligonucleotide was
      also tested in parallel. A specific decrease of IK transcripts was correlated
      with an increase of HLA-DR antigen expression level. In colony-forming assays, IK
      antisense oligonucleotide inhibited colony formation by multilineage early
      erythroid and granulomonocytic CD34+ progenitors. The mean colony size was
      decreased 70% by IK antisense oligonucleotide in comparison to controls. These
      results provide evidence that the IK molecule participates in the regulation of
      HLA-DR expression on hematopoietic cells and plays a role in growth factor
      dependent CD34+ cell proliferation and differentiation by modulating HLA-DR
      expression.

PMID- 9160667
TI  - A role for the Wnt gene family in hematopoiesis: expansion of multilineage
      progenitor cells.
AB  - The microenvironment is a key regulator of hematopoietic stem cells (HSCs) and is
      a likely source of extracellular factors that control stem cell fate. A better
      understanding of these microenvironmental factors may come from investigations of
      developmental cell fate determination in which the critical roles of cell-cell
      interactions of multipotential cells have been shown. The Wnt gene family is
      known to regulate the cell fate and cell-cell interactions of multipotential
      cells in a variety of tissues. Expression of Wnts and of their putative receptors
      encoded by murine homologs of the Drosophila frizzled gene in hematopoietic
      tissues was examined by reverse transcriptase-polymerase chain reaction. Wnt-5a
      and Wnt-10b were expressed in day-11 murine yolk sac, day-14 fetal liver, and
      fetal liver AA4+ cells. The expression profiles of four murine frizzled homologs,
      Mfz3-7, were nearly identical to that of Wnt-5a and Wnt-10b. Notably, Wnt-10b was
      expressed in the fetal liver AA4+ Sca+ c-kit+ flASK) HSC population. A role for
      Wnts in HSC fate determination was studied by treatment of HSC populations in
      culture with soluble WNT proteins. The addition of conditioned media from cells
      transfected with Wnt-1, Wnt-5a, or Wnt-10b cDNAs to cultures of flASK cells
      stimulated a sevenfold, eightfold, and 11-fold expansion in cell number,
      respectively, relative to control media. Removal of WNT-5a from this media by
      immunodepletion depleted the stimulatory activity from the media, whereas
      addition of a partially purified WNT-5a stimulated a fivefold expansion relative
      to control cells. Transduction of flASK cells with a retrovirus bearing a Wnt-5a
      cDNA enhanced proliferation. We conclude that WNTs stimulate the
      survival/proliferation of hematopoietic progenitors, demonstrating that WNTs
      comprise a novel class of hematopoietic cell regulators.

PMID- 9160668
TI  - Transcription factor GATA-2 is required for proliferation/survival of early
      hematopoietic cells and mast cell formation, but not for erythroid and myeloid
      terminal differentiation.
AB  - The zinc-finger transcription factor GATA-2 plays a critical role in maintaining
      the pool of early hematopoietic cells. To define its specific functions in the
      proliferation, survival, and differentiation of hematopoietic cells, we analyzed
      the hematopoietic potential of GATA-2-/- cells in in vitro culture systems for
      proliferation and maintenance of uncommitted progenitors or differentiation of
      specific lineages. From a two-step in vitro differentiation assay of embryonic
      stem cells and in vitro culture of yolk sac cells, we demonstrate that GATA-2 is
      required for the expansion of multipotential hematopoietic progenitors and the
      formation of mast cells, but dispensable for the terminal differentiation of
      erythroid cells and macrophages. The rare GATA-2-/- multipotential progenitors
      that survive proliferate poorly and generate small colonies with extensive cell
      death, implying that GATA-2 may play a role in both the proliferation and
      survival of early hematopoietic cells. To explore possible mechanisms resulting
      in the hematopoietic defects of GATA-2-/- cells, we interbred mutant mouse
      strains to assess the effects of p53 loss on the behavior of GATA-2-/-
      hematopoietic cells. Analysis of GATA-2-/-/p53-/- compound-mutant embryos shows
      that the absence of p53 partially restores the number of total GATA-2-/-
      hematopoietic cells, and therefore suggests a potential link between GATA-2 and
      p53 pathways.

PMID- 9160669
TI  - Immature human megakaryocytes produce nuclear-associated acetylcholinesterase.
AB  - Acetylcholinesterase (AChE) is expressed in murine megakaryocytes (MK), where its
      antisense inhibition suppresses differentiation, yet was never detected in human
      MK. Here, we report that AChE is produced in normal human bone marrow MK and in
      cell lines derived thereof. Reverse transcriptase-polymerase chain reaction (RT
      PCR) amplification showed two ACHEmRNA forms in human megakaryoblastic DAMI
      cells. In situ hybridization demonstrated ACHEmRNA surrounding the nucleus of
      small DAMI cells and the nuclear lobes of large, polyploid cells. Differentiation
      induction with phorbol ester and exposure to recombinant human thrombopoietin
      suppressed both ACHEmRNA and AChE activity. The residual AChE in mature
      differentiated cells acquired higher stability and detergent-sensitivity as
      compared with AChE in small proliferating cells. AChE activity was primarily
      associated with nuclei of both DAMI cells and small (10 microm) primary
      proliferating human bone marrow MK identified with GPIIb/IIIa antibodies. This
      activity was significantly reduced in medium size MK (10 to 25 microm) and was
      almost undetectable in large MK (>25 microm), yet was twofold more abundant in
      some large MK from idiopathic thrombocytopenia purpura (ITP) patients with
      accelerated MK maturation. The loss of AChE activity at the transition from
      proliferating to differentiating MK highlights species-specific differences in
      its expression, suggesting a distinct role for AChE in human MK development.

PMID- 9160670
TI  - Glanzmann thrombasthenia caused by an 11.2-kb deletion in the glycoprotein IIIa
      (beta3) is a second mutation in Iraqi Jews that stemmed from a distinct founder.
AB  - Glanzmann thrombasthenia (GT) is a rare bleeding disorder resulting from
      mutations in either glycoprotein (GP) IIb or GPIIIa genes. The disease is
      relatively frequent in highly inbred populations such as Iraqi Jews. The
      molecular basis of GT in 6 unrelated Iraqi-Jewish patients was previously
      identified as an 11-bp deletion in exon 12 of the GPIIIa gene. We now describe a
      second mutation found in 3 unrelated Iraqi-Jewish families that consists of an
      11.2-kb deletion between an Alu repeat in intron 9 and exon 13 of the GPIIIa
      gene. The mutant DNA is transcribed into mRNA in which exons 10 through 13 are
      absent. Splicing of exon 9 directly to exon 14 leads to a shift in the reading
      frame resulting in a stop codon. The predicted protein is truncated in the middle
      of the third cysteine-rich domain before the transmembrane domain. Simple DNA
      based methods were devised for identification of both mutations in Iraqi Jews for
      the purpose of carrier detection and prenatal diagnosis enabling prevention of
      GT. A survey of the general Iraqi-Jewish population for the first 11-bp deletion
      and the second 11.2-kb deletion disclosed that the allele frequency of the first
      mutation was 0.0043, whereas none of 700 individuals examined bore the second
      mutation (allele frequency <0.0007). Among 40 GT patients of Iraqi-Jewish origin
      31 were homozygous for the first mutation, 4 were compound heterozygotes for the
      first and second mutations, and 2 were homozygous for the second mutation.
      Haplotype analyses using 4 polymorphic markers in the GPIIIa gene showed that
      each mutation originated in a distinct founder.

PMID- 9160671
TI  - The inhibitor antibody response is more complex in hemophilia A patients than in
      most nonhemophiliacs with factor VIII autoantibodies. Recombinate and Kogenate
      Study Groups.
AB  - Approximately 25% of hemophilia A patients infused with factor VIII (fVIII) mount
      an immune response, which leads to its inactivation. Anti-fVIII autoantibodies
      are also seen rarely in individuals with normal fVIII. We have previously
      demonstrated that some anti-A2 and anti-C2 domain antibodies are fVIII inhibitors
      and that many patients have additional inhibitors with a fVIII light chain (LCh)
      epitope outside C2. Because the contribution of the different antibodies to the
      plasma inhibitor titer had been examined in a limited number of patients (14), we
      report in this study a more extensive analysis of 55 plasmas. The dominant
      inhibitors in 62% (13 of 21) of autoantibody plasmas were directed only against
      C2 or A2, but not both, whereas this pattern was found in only 15% (5 of 34) of
      hemophilic plasmas. In addition, anti-A2 inhibitors were present in 71% (24 of
      34) of hemophilic plasmas, but only 33% (7 of 21) of autoantibody plasmas. These
      results demonstrated that the inhibitor response in hemophiliacs was more complex
      and the epitope specificity was somewhat different. A comparison of hemophiliacs
      treated only with plasma fVIII or recombinant fVIII showed no significant
      differences in the complexity of the inhibitor response, as > or = 2 different
      inhibitor antibodies were present in 78% (18 of 23) of the former and 82% (9 of
      11) of the latter. In contrast, the major inhibitors in 35% (8 of 23) of
      hemophiliacs treated with plasma fVIII were directed against C2 and another LCh
      epitope within residues 1649-2137, but not A2, while none (0 of 11) treated with
      recombinant fVIII had this pattern.

PMID- 9160672
TI  - Functional characterization and modulation of cytokine production by CD8+ T cells
      from human immunodeficiency virus-infected individuals.
AB  - CD8+ T-cell clones were generated from peripheral blood mononuclear cells (PBMC)
      of three human immunodeficiency virus (HIV)-seronegative individuals and six HIV
      seropositive individuals and assessed for their cytokine secretion profile,
      cytolytic potential, and chemokine production. While the great majority of CD8+ T
      cell clones generated from HIV-seronegative individuals produced interferon (IFN)
      gamma, but not interleukin-4 (IL-4), that is a type 1 cytotoxic (Tc1) profile,
      high numbers of CD8+ T-cell clones generated from HIV-seropositive individuals
      produced IL-4 in addition to IFN-gamma or IL-4 alone, thus showing a type 0
      cytotoxic (Tc0)- or a type 2 cytotoxic (Tc2) profile, respectively. Tc0/Tc2 cells
      displayed lower cytolytic activity than Tc1 cells, including a reduced ability to
      lyse autologous targets pulsed with HIV or HIV peptides. By contrast, the
      production of chemokines RANTES and macrophage inflammatory protein-1alpha was
      comparable in Tc1, Tc0, and Tc2 clones irrespective of whether they were derived
      from HIV-seronegative or HIV-seropositive individuals. When CD8+ T-cell clones
      were generated from PBMC cultures of HIV-seronegative individuals conditioned
      with IL-4 plus an anti-IL-12 antibody (Ab), a shift towards the Tc0/Tc2-like
      profile was observed. Conversely, the addition to PBMC cultures of IL-12 plus an
      anti-IL-4 Ab shifted the differentiation of CD8+ T cells from HIV-infected
      individuals towards the Tc1-like profile, whereas IL-12 or anti-IL-4 Ab alone had
      a lower Tc1-promoting effect. Irradiated PBMC from HIV-infected individuals, used
      as feeder cells, shifted the differentiation of CD8+ T cells from a healthy HIV
      seronegative individual towards the Tc0/Tc2-like profile. On the other hand, a
      shift towards the Tcl-like profile was noted in CD8+ T-cell clones generated from
      the skin specimens of two HIV-seropositive patients with Kaposi's sarcoma,
      successfully treated with IFN-alpha, in comparison to CD8+ clones generated from
      the same skin areas before treatment. The IFN-alpha-induced Tc1 shift could be
      prevented by the incubation of skin-infiltrating CD8+ T cells with IL-4 before
      cloning. Taken together, these data indicate that both defective production of IL
      12 and abnormal IL-4 production in bulk PBMC populations of HIV-infected
      individuals may contribute to the development of high numbers of CD8+ T-cell
      clones showing a Tc0/Tc2-like phenotype and reduced cytolytic potential against
      HIV itself. They also suggest that the cytokine profile of CD8+ T-cell clones can
      be modulated by cytokines (or anticytokine Ab) both in vitro and in vivo.

PMID- 9160673
TI  - Pentoxifylline promotes replication of human cytomegalovirus in vivo and in
      vitro.
AB  - OKT3 monoclonal antibody (MoAb) therapy is well established in the prevention and
      therapy of acute rejection in transplant patients. Unfortunately, this therapy is
      associated with several short-term (cytokine release syndrome) and long-term
      (infections, EBV-related lymphoma) side effects. Recently, we were able to
      demonstrate an association between the TNF alpha release following the first OKT3
      MoAb infusions and the appearance of human cytomegalovirus (HCMV) reactivation
      several days later. In order to prevent this TNF alpha associated HCMV
      reactivation patients were additionally treated with pentoxifylline (PTX), a
      methylxanthine derivative that has been shown to suppress TNF alpha induction.
      Although the TNF alpha peak plasma level following OKT3 MoAb treatment was
      markedly reduced, the incidence of HCMV reactivation and HCMV disease was not
      influenced. In transient transfection experiments using HCMV immediate early
      enhancer/promoter CAT reporter gene constructs PTX enhanced the promoter activity
      independently from TNF alpha in premonocytic cells. Furthermore, PTX acted
      synergistically with TNF alpha. In virus-infected human embryonal lung
      fibroblasts HCMV replication was triggered in the presence of both PTX and TNF
      alpha, while either substance alone had only marginal effects. The stimulatory
      effect of PTX on the immediate early (IE) enhancer/promoter was mediated via
      CREB/ ATF, a eukaryotic transcription factor that binds to the 19 bp sequence
      motif in the enhancer region, while TNF alpha stimulation was mediated by
      activation of the transcription factor NF-kappaB and its binding to the 18 bp
      sequence motif in the enhancer. These data suggest a potential side effect of
      cAMP-elevating drugs such as PTX.

PMID- 9160674
TI  - Isolation of a T-cell clone showing HLA-DRB1*0405-restricted cytotoxicity for
      hematopoietic cells in a patient with aplastic anemia.
AB  - The existence of T cells capable of inhibiting in vitro hematopoiesis has been
      shown in aplastic anemia (AA), although whether such inhibition is mediated by a
      specific immune reaction involving an HLA allele remained unknown. We isolated a
      CD4+ Vbeta21+ T-cell clone that was most dominant among Vbeta21+ T cells in the
      bone marrow (BM) of an AA patient whose HLA-DRB1 alleles included 1501 and 0405.
      The T-cell clone named NT4.2 lysed an autologous Epstein-Barr virus-transformed
      lymphoblastoid cell line (LCL) and phytohemagglutinin-stimulated lymphocytes (PHA
      blasts) as well as allogeneic LCLs sharing HLA-DRB1*0405. Cytotoxicity against
      LCL cells and PHA-blasts by NT4.2 was blocked by anti-HLA-DR monoclonal antibody
      (MoAb) or anti-CD3 MoAb. NT4.2 also lysed autologous BM mononuclear cells
      enriched with CD34+ cells that had been cultured for one week in the presence of
      colony-stimulating factors as well as allogeneic CD34+ cells of a normal
      individual carrying HLA-DRB1*0405, cultured in the same way. Moreover, NT4.2
      strongly inhibited colony formation by hematopoietic progenitor cells derived
      from cultured CD34+ cells sharing HLA-DRB1*0405. These results indicate that the
      AA patient has T cells capable of killing hematopoietic cells in an HLA-DRB1*0405
      restricted manner and that such cytotoxic T cells may contribute to the
      pathogenesis of AA.

PMID- 9160675
TI  - Distinctions between CD8+ and CD4+ T-cell regenerative pathways result in
      prolonged T-cell subset imbalance after intensive chemotherapy.
AB  - Rapid recovery of CD4+ T cells after intensive chemotherapy is limited by an age
      dependent decline in thymopoiesis. Here we sought to determine whether similar
      limitations exist for CD8+ T-cell regeneration. After intensive chemotherapy,
      CD8+ T cells had a faster effective doubling time than CD4+ T cells (median, 12.6
      v 28.2 days, P < .05). Accordingly, at 3 months posttherapy, mean CD8+ T-cell
      number had returned to baseline, whereas mean CD4+ T-cell number was only 35% of
      pretherapy values (P < .05). These differences were primarily due to very rapid
      expansion of CD8+CD57+ and CD8+CD28- subsets. At 3 months posttherapy, there was
      no relationship between age and CD8+ T-cell number (R = -.02), whereas CD4+ T
      cell number was inversely related to age (R = -.66) and there were no discernible
      differences in CD8+ recovery among patients with or without thymic enlargement,
      whereas CD4+ recovery was enhanced in patients with thymic enlargement after
      chemotherapy (P < .01). Therefore thymic-independent pathways of T-cell
      regeneration appear to rapidly regenerate substantial numbers of CD8+, but not
      CD4+ T cells, resulting in prolonged T-cell subset imbalance after T-cell
      depletion. These inherent distinctions between CD4+ v CD8+ T-cell regeneration
      may have significant implications for immunotherapeutic strategies undertaken to
      eradicate minimal residual neoplastic disease after cytoreductive chemotherapy.

PMID- 9160676
TI  - Isolation of human blood dendritic cells using the CMRF-44 monoclonal antibody:
      implications for studies on antigen-presenting cell function and immunotherapy.
AB  - Dendritic cells (DC) are potent antigen-presenting cells (APC) with the capacity
      to stimulate a primary T lymphocyte immune response and are therefore of interest
      for potential immunotherapeutic applications. Freshly isolated DC or DC
      precursors may be preferable for studies of antigen uptake and the potential
      control of APC costimulator activity. In this report, we report that the
      monoclonal antibody CMRF-44 can be used to detect early DC differentiation. The
      majority of DC circulating in blood do not express any known DC lineage specific
      markers, but can be identified by CMRF-44 labeling after a brief period of in
      vitro culture. The sequential acquisition of DC activation antigens allows the
      identification of two stages of DC maturation/activation. Cytokines, especially
      granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis
      factor (TNF)alpha, enhance both phases of this process, whereas CD40-ligand
      trimer preferentially enhances the final DC maturation to a fully mature,
      activated phenotype. DC positively selected using CMRF-44 possess potent
      allostimulatory activity and are efficient at the uptake, processing, and
      presentation of soluble antigens for both primary and secondary immune responses.
      CMRF-44+ DC are also more potent than other APC types at restimulation of a
      chronic myeloid leukemia peptide specific T-cell clone. The use of a purified
      population of freshly isolated DC may be advantageous in attempts to initiate,
      maintain, and direct immune responses for immunotherapeutic applications.

PMID- 9160677
TI  - CD2 rescues T cells from T-cell receptor/CD3 apoptosis: a role for the Fas/Fas-L
      system.
AB  - Anti-CD3 monoclonal antibodies (MoAbs) and glucocorticoid hormones induce
      apoptosis in immature thymocytes and peripheral T lymphocytes. This process is
      inhibited by a number of growth factors, including interleukin-2 (IL-2), IL-3,
      and IL-4, as well as by triggering of the adhesion molecule CD44, which would
      indicate that signals generated by membrane receptors can modulate the survival
      of lymphoid cells. To investigate whether triggering of CD2 may also affect
      apoptosis in lymphoid cells, we analyzed the effect of stimulation with anti-CD2
      MoAbs on T-cell apoptosis induced by two stimuli, anti-CD3 MoAbs and
      dexamethasone (DEX), using a hybridoma T-cell line and a T-helper cell clone. The
      results show that CD2 engagement decreased anti-CD3 MoAb-induced apoptosis, but
      did not influence DEX-induced cell death. Furthermore, the decrease appeared to
      be related to the expression of Fas/APO-1 (CD95) and Fas-ligand (Fas-L). In fact,
      we show that CD2 stimulation inhibits apoptosis by preventing the CD3-induced
      upregulation of Fas and Fas-L in a Fas-dependent experimental system. These data
      suggest that a costimulatory molecule may control a deletion pathway and may
      therefore contribute to the regulation of peripheral tolerance.

PMID- 9160678
TI  - Effect of a recombinant dimeric tumor necrosis factor receptor on inflammatory
      responses to intravenous endotoxin in normal humans.
AB  - To determine the role of tumor necrosis factor (TNF) in lipopolysaccharide (LPS)
      induced inflammation, 12 healthy subjects received an intravenous injection with
      LPS (2 ng/kg) preceded by infusion of either a recombinant human dimeric TNF
      receptor type II-IgG fusion protein (TNFR:Fc; 6 mg/m2; n = 6) or vehicle (n = 6)
      from -30 minutes to directly before LPS injection. LPS elicited a transient
      increase in plasma TNF activity, peaking after 1.5 hours (219 +/- 42 pg/mL; P <
      .05). Infusion of TNFR:Fc completely neutralized endogenous TNF activity. LPS
      administration was associated with an early activation of fibrinolysis (plasma
      concentrations of tissue-type plasminogen activator, plasminogen activator
      activity, and plasmin-alpha2-antiplasmin complexes), followed by inhibition
      (plasma plasminogen activator inhibitor type I), changes that were completely
      prevented by TNFR:Fc. By contrast, TNFR:Fc did not influence LPS-induced
      activation of coagulation (plasma levels of prothrombin fragment F1 + 2 and
      thrombin-antithrombin III complexes). TNFR:Fc strongly inhibited endothelial cell
      activation (plasma levels of soluble E-selectin), modestly reduced neutrophil
      responses (neutrophilia and plasma concentrations of elastase-alpha1-antitrypsin
      complexes and lactoferrin), but did not affect the release of secretory
      phospholipase A2 or lipopolysaccharide-binding protein (P > .05). Infusion of
      TNFR:Fc only (without LPS) in another 6 normal subjects did not induce any
      inflammatory response. These data indicate that TNF is involved in only some
      inflammatory responses to intravenous LPS in humans.

PMID- 9160679
TI  - Prevalence and growth characteristics of malignant stem cells in B-lineage acute
      lymphoblastic leukemia.
AB  - We used a stroma-supported culture method to study the prevalence and growth
      characteristics of malignant stem cells in acute lymphoblastic leukemia (ALL). In
      51 of 108 B-lineage ALL samples, bone marrow-derived stroma not only inhibited
      apoptosis of ALL cells but also supported their proliferation in serum-free
      medium. When single leukemic cells were placed in the stroma-coated wells of
      microtiter plates, the percentage of wells with leukemic cell growth after 2 to 5
      months of culture ranged from 6% to 20% (median, 15%; 5 experiments). The
      immunophenotypes and genetic features of cells recovered from these cultures were
      identical to those noted before culture. All cells maintained their stroma
      dependency and self-renewal capacity. Leukemic clones derived from single cells
      contained approximately 10(3) to 10(6) cells after 1 month of culture; other
      clones became detectable only after prolonged culture. Cell growth in stroma
      coated wells correlated with the number of initially seeded cells (1 or 10; r =
      .87). However, the observed percentages of positive wells seeded with 10 cells
      always exceeded values predicted from results with single-cell-initiated cultures
      (P < .003 by paired t-test), suggesting stimulation of leukemic cell growth by
      paracrine factors. In conclusion, the proportion of ALL cells with clonogenic
      potential may be considerably higher than previously thought.

PMID- 9160680
TI  - Vesicular anthracycline accumulation in doxorubicin-selected U-937 cells:
      participation of lysosomes.
AB  - The U-A10 cell line, a doxorubicin-selected variant of human U-937 myeloid
      leukemia cells, exhibits a redistribution of anthracyclines into a expanded
      vesicular compartment. The acidic nature of this compartment was confirmed by
      vital staining with a pH sensitive dye, LysoSensor yellow/blue DND-160.
      Identification of the vesicular compartment was performed by immunofluorescence
      analysis. Staining for the LAMP-1 and LAMP-2 antigens showed that the vesicles
      are enlarged lysosomes that are eccentrically placed near the nucleus of U-A10
      cells. By contrast, the expression of the multidrug resistance-associated protein
      and the P-glycoprotein was observed predominately on the plasma membrane of the
      drug-resistant cells. The accumulation of daunorubicin into cellular compartments
      was quantified using radiolabeled drug. Exposing cells to 3[H]-daunorubicin and
      then isolating intact nuclei showed that nuclei from U-A10 cells accumulated
      twofold to threefold less anthracycline than nuclei from U-937 cells. However,
      when nuclei were isolated first and then exposed to 3[H]-daunorubicin, little
      difference in net nuclear drug accumulation was detected. Cytoplasts prepared
      from U-A10 and U-937 cells were exposed to 3[H]-daunorubicin to measure
      cytoplasmic drug accumulation. At external daunorubicin concentrations of 100
      ng/mL or higher, cytoplasts from U-A10 cells accumulated significantly more
      daunorubicin than cytoplasts from U-937 cells. Moreover, studies with the
      lysosomotropic agent chloroquine showed that U-A10 cells accumulated twofold more
      chloroquine and showed twofold enhanced sensitivity to this agent as compared
      with parental U-937 cells. Fluorescence microscopy showed that chloroquine
      affects vesicular anthracycline sequestration in U-A10 cells with an associated
      increase in daunorubicin nuclear fluorescence. Although chloroquine did not alter
      anthracycline cytotoxicity in parental cells, it restored daunorubicin and
      doxorubicin sensitivity to U-A10 cells. Taken together, these studies demonstrate
      that U-A10 cells exhibit a redistribution of the lysosomal compartment. The
      trapping of drug into an expanded acidic vesicular compartment results in
      decreased nuclear drug accumulation and decreased cytotoxicity. Lysosomotropic
      agents, such as chloroquine, warrant further study as modulators of this acquired
      drug-resistance phenotype.

PMID- 9160682
TI  - Lack of t(14;18) polymerase chain reaction-positive cells in highly purified
      CD34+ cells and their CD19 subsets in patients with follicular lymphoma.
AB  - Follicular lymphoma (FL) is characterized in a significant proportion of cases by
      the t(14;18) chromosomal translocation, which results in the juxtaposition of the
      oncogene bcl-2 to the joining region of the immunoglobulin heavy chain (IgH)
      gene. Molecular sequence analysis indicates that the t(14;18) rearrangement
      occurs in a B-lymphoid progenitor cell at the time of IgH rearrangement. We were
      interested whether hematopoietic stem and progenitor cells as characterized by
      CD34 expression bear the translocation. Bone marrow (BM)-CD34+ cells were
      enriched from 14 patients with FL whose BM was known to be positive for bcl-2/IgH
      (major breakpoint region [MBR]). Six patients were in complete remission (CR),
      two patients were in partial remission (PR), and six patients had active disease.
      Six patients had histological BM involvement when the samples were obtained.
      Using an immunomagnetic selection device (MINI-MACS), a mean purity of 88.7% +/-
      4% CD34+ cells was achieved. The CD34+ cells were further enriched by
      fluorescence activated cell sorting (FACS) using CD34 fluorescein isothiocyanate
      (FITC)- and CD19 phycoerythrin (PE)-conjugated antibodies. The IgH gene was
      rearranged in the CD34+/CD19+ cell subset of all patients assessed by polymerase
      chain reaction (PCR). This population is thought to represent the progenitor
      stage at which the bcl-2/IgH translocation occurs. The unseparated BM mononuclear
      cell fraction from all 14 patients was positive for bcl-2/IgH using a nested PCR,
      but the BM-CD34+ cell fraction and the respective CD34+/CD19+ subset were
      negative in 13 of these 14 patients. The one patient with a positive PCR signal
      in the CD34+ cell subset had a relapse with BM involvement. We conclude that
      CD34+ progenitor cells including CD34+/CD19+ B-cell progenitors are not involved
      in the malignant cell clone. These data are in agreement with a transgenic mouse
      model, which indicates that the malignant phenotype in FL is sustained by mature
      B cells.

PMID- 9160681
TI  - Frequent mutation of the 5' noncoding region of the BCL-6 gene in acquired
      immunodeficiency syndrome-related non-Hodgkin's lymphomas.
AB  - Acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphomas (AIDS
      NHL), a major source of morbidity and mortality among human immunodeficiency
      virus (HIV)-infected individuals, are derived from B cells and are classified
      into two major categories, Burkitt's lymphoma (BL) and diffuse large cell
      lymphoma (DLCL). Anaplastic large cell lymphoma (ALCL) and body-cavity-based
      lymphoma (BCBL) represent less frequent AIDS-NHL types. The molecular
      pathogenesis of AIDS-NHL is characterized by distinct genetic pathways, including
      chromosomal rearrangements of c-MYC and BCL-6 in AIDS-BL and AIDS-DLCL,
      respectively. In addition to gross rearrangements, recent evidence has suggested
      that BCL-6 may also be affected by mutations of the gene 5' noncoding regions.
      Here we have investigated the distribution of BCL-6 mutations in a panel
      representative of all the AIDS-NHL subtypes. Forty-three AIDS-NHL were analyzed
      for mutations in the first exon-first intron boundary region of BCL-6. Mutations
      were detected in all categories of AIDS-NHL (25 of 43 cases; 58%), including 12
      of 20 AIDS-BL, 10 of 15 AIDS-DLCL, two of three AIDS-ALCL, and one of five of
      AIDS-BCBL. BCL-6 mutations occurred independent of BCL-6 rearrangements and
      presence of other genetic lesions frequently associated with AIDS-NHL. These
      results indicate that mutations of BCL-65' noncoding regions represent the most
      common genetic alteration presently detectable in AIDS-NHL. The frequency of
      these mutations, as well as their location in the proximity of BCL-6 regulatory
      sequences, suggest that they may play a role in AIDS-related lymphomagenesis.

PMID- 9160683
TI  - Cellular expression of antiapoptotic BCL-2 oncoprotein in newly diagnosed
      childhood acute lymphoblastic leukemia: a Children's Cancer Group Study.
AB  - We found a marked variation in BCL-2 oncoprotein expression levels of primary
      leukemic cells from 338 children with newly diagnosed acute lymphoblastic
      leukemia (ALL). None of the high-risk features predictive of poor treatment
      outcome in childhood ALL, such as older age, high white blood cell (WBC) count,
      organomegaly, T-lineage immunophenotype, ability of leukemic cells to cause overt
      leukemia in severe combined immunodeficient (SCID) mice, presence of MLL-AF4, and
      BCR-ABL fusion transcripts were associated with high levels of BCL-2 expression.
      Overall, high BCL-2 levels were not associated with slow early response, failure
      to achieve complete remission, or poor event-free survival. High BCL-2 levels in
      primary leukemic cells predicted slow early response only in T-lineage ALL
      patients, which comprised approximately 15% of the total patient population. Even
      for this small subset of patients, the level of BCL-2 expression did not have a
      significant impact on the short-term event-free survival.

PMID- 9160684
TI  - Quantitative analysis of apoptotic cell death using proton nuclear magnetic
      resonance spectroscopy.
AB  - Quantification of apoptotic cell death in vivo has become an important area of
      investigation in patients with acute lymphoblastic leukemia (ALL). We have
      devised a noninvasive analytical method to estimate the percentage of apoptotic
      lymphoblasts in doxorubicin-treated Jurkat T-cell ALL cultures, using proton
      nuclear magnetic resonance spectroscopy (1H NMR). We have found that the ratio of
      the methylene (CH2) resonance (at 1.3 ppm) to the methyl (CH3) resonance (at 0.9
      ppm) signal intensity, as observed by 1H NMR, is directly proportional to the
      percentage of apoptotic lymphoblasts in vitro. The correlation between the
      CH2/CH3 signal intensity ratio and the percentage of apoptotic lymphoblasts was
      optimal 24 to 28 hours after doxorubicin treatment (r2 = .947, N = 27 samples).
      There was also a direct temporal relationship between an increase in the CH2/CH3
      signal intensity ratio and the onset of apoptosis as detected by nuclear
      morphologic analysis, fluorescein-annexin V flow cytometry, and DNA gel
      electrophoresis. Thin-layer chromatography confirmed that a dynamic and/or
      compositional change of the plasma membrane, rather than increases in lipase
      activity or fatty acid production, appears to account for the increase in the
      CH2/CH3 signal intensity ratio during apoptosis. 1H NMR may have clinical utility
      for the early noninvasive assessment of chemotherapeutic efficacy in patients
      with ALL.

PMID- 9160685
TI  - Reed-Sternberg cells of classical Hodgkin's disease react with the plasma cell
      specific monoclonal antibody B-B4 and express human syndecan-1.
AB  - Although the cellular origin of Reed-Sternberg (RS) cells of classical Hodgkin's
      disease (HD) has been a controversial issue for many years, recent
      immunophenotypic and molecular studies have suggested that RS cells of a subset
      of classical HD cases may be related to B cells. To further define the
      immunophenotypic features and the differentiation stage of RS cells, a series of
      56 HD samples, including both nodular lymphocyte predominance (LP) (eight cases)
      and classical HD (nodular sclerosis [NS], 32 cases; mixed cellularity [MC], 16
      cases) with a non-T-cell phenotype, were evaluated for the immunohistochemical
      expression of the B-B4 antigen, a specific marker for terminally differentiated B
      cells. Because the cDNA of the B-B4 antigen encodes syndecan-1, a member of a
      family of transmembrane heparan sulfate proteoglycans thought to be involved in
      binding cells of the B lineage to the interstitial matrix, the B-B4
      immunoreactivity was correlated with the expression of syndecan-1 in HD-derived
      cell lines (L428, KM-H2), as detected by both reverse transcriptase polymerase
      chain reaction (RT-PCR) studies and Western blotting. Our results show that B-B4
      reacts with RS cells and their morphological variants of all cases of classical
      HD, irrespective of their antigenic phenotype (B, undetermined), albeit at a
      varying degree of cellular expression. Notably, a high reactivity and staining
      intensity for the B-B4 monoclonal antibody (MoAb) was restricted to tumor cells
      from NS HD. In cases of the latter subtype, B-B4 positivity was also found in
      sclerosis-trapped spindle cells (fibrocytes/fibroblasts). Conversely, the
      putative tumor cells of nodular LP HD were consistently unreactive with the B-B4
      MoAb. Finally, we have demonstrated by RT-PCR, flow cytometry, and Western
      blotting that cultured RS cells, of B and undetermined phenotype, express
      syndecan-1 mRNA and produce a form of syndecan-1, recognized by the B-B4 MoAb,
      which is predominantly associated with glycosaminoglycans and is present at the
      cell surface. Our detection of the plasma cell-specific antigen B-B4 (syndecan-1)
      on tumor cells of classical HD further supports that RS cell progenitors may be
      related to germinal/postgerminal center mature B cells and suggests that
      expression of syndecan-1 may contribute to some of the typical biologic and
      histopathologic features of classical HD, with a special regard to the NS
      subtype.

PMID- 9160686
TI  - Expression of the multidrug resistance-associated protein gene in refractory
      lymphoma: quantitation by a validated polymerase chain reaction assay.
AB  - Previous work investigating the role of MDR-1 overexpression in relapsed and
      refractory lymphoma led us to investigate a possible role for multidrug
      resistance-associated protein (MRP) as a cause of resistance in patients who did
      not overexpress MDR-1. A quantitative polymerase chain reaction (PCR) method for
      measuring MRP expression was validated. Immunoblot analysis suggested that no
      major discrepancy was present between mRNA expression and protein levels. MRP
      levels were found to be independent of sample tumor content by immunophenotyping,
      suggesting that the presence of normal cells had no significant impact on
      measurements of MRP expression. We evaluated MRP in 55 biopsy samples from 40
      patients with refractory lymphoma enrolled on a trial of infusional chemotherapy
      (EPOCH). Pre- and post-EPOCH samples were available from 15 patients. MRP levels
      were also evaluated in 16 newly diagnosed, untreated lymphoma patient samples. No
      significant difference in MRP mRNA expression was noted between pre- and post
      EPOCH groups. Also, MRP levels in the newly diagnosed patient samples were not
      significantly different from either pre- or post-EPOCH groups. Two of 15 paired
      pre- and post-EPOCH patient samples exhibited overexpression of MRP after EPOCH
      chemotherapy, with measured increases of 10-fold and 18-fold. We conclude that
      MRP overexpression is not responsible for non-P-glycoprotein (Pgp)-mediated drug
      resistance in the majority of these patients, although it may be important in a
      subset of patients. Defining this subset prospectively could aid in the
      development of clinical trials of MRP modulation in drug-resistant lymphoma.

PMID- 9160687
TI  - MLL gene rearrangement, cytogenetic 11q23 abnormalities, and expression of the
      NG2 molecule in infant acute myeloid leukemia.
AB  - To study prognostic factors in infant acute myeloid leukemia (AML), we analyzed
      44 children treated on Childrens Cancer Group protocols for MLL gene
      rearrangement by Southern blot, cytogenetic 11q23 abnormalities, and reactivity
      with monoclonal antibody 7.1. This antibody detects the human homologue of the
      rat NG2 chondroitin sulfate proteoglycan molecule, which has previously been
      reported to be expressed on human melanoma. NG2 has been found to be expressed on
      human leukemic blasts but not on other hematopoietic cells. In childhood AML, NG2
      cell surface expression correlated with poor outcome and with some but not all
      11q23 rearrangements. In childhood acute lymphoblastic leukemia, NG2 expression
      correlated with poor outcome and with balanced 11q23 translocations. In this
      study, 29 of 44 (66%) of infants with AML showed MLL rearrangement and, as
      expected, this group had a high incidence of French-American-British M4/M5
      morphology (22/29). Of the cases tested, 35.1% (13/37) were NG2 positive. All
      (13/13) NG2-positive cases were rearranged at MLL, whereas only 46% (11/24) of
      NG2-negative cases had MLL rearrangement. NG2 expression did not correlate with
      poor outcome (P = .31); there was a trend towards a worse outcome with MLL
      rearrangement (P = .13). Thus monoclonal antibody 7.1 does not detect all cases
      of MLL rearrangement in infant AML.

PMID- 9160688
TI  - Autologous tumor infiltrating T cells cytotoxic for follicular lymphoma cells can
      be expanded in vitro.
AB  - Follicular lymphomas (FLs) rarely induce clinically significant T-cell-mediated
      responses. We showed that freshly isolated tumor infiltrating T cells (T-TILs)
      lack tumor-specific cytotoxicity. Stimulation of these T cells with FL cells in
      the presence of interleukin-2 (IL-2) and/or costimulation via CD28 does not lead
      to T-cell activation and expansion. In contrast, when stimulated with FL cells
      preactivated via CD40, autologous T-TILs can be expanded by the addition of
      exogenous IL-2. These T cells can be further expanded in vitro by the addition of
      exogenous IL-4, IL-7, or interferon-gamma, but not IL-12. Once activated, these T
      cells showed FL-directed cytotoxicity in four of five patients tested. We
      concluded that autologous cytotoxic anti-FL-specific T cells exist, but can only
      be detected in vitro under optimized conditions for T-cell stimulation and
      expansion. This suggests that their frequency in vivo is either very low or that
      the microenvironment does not provide the necessary signals to activate these T
      cells. This model system allows dissection of the requisite conditions for
      activation and expansion of lymphoma-directed cytotoxicity and may permit
      expansion of previously activated cytotoxic T cells for adoptive transfer.

PMID- 9160689
TI  - Immunolocalization of the ICE/Ced-3-family protease, CPP32 (Caspase-3), in non
      Hodgkin's lymphomas, chronic lymphocytic leukemias, and reactive lymph nodes.
AB  - Immunohistochemical analysis of the apoptosis-effector protease CPP32 (Caspase-3)
      in normal lymph nodes, tonsils, and nodes affected with reactive hyperplasia (n =
      22) showed strong immunoreactivity in the apoptosis-prone germinal center B
      lymphocytes of secondary follicles, but little or no reactivity in the
      surrounding long-lived mantle zone lymphocytes. Immunoblot analysis of
      fluorescence-activated cell sorted germinal center and mantle zone B cells
      supported the immunohistochemical results. In 22 of 27 (81%) follicular small
      cleaved cell non-Hodgkin's B-cell lymphomas, the CPP32-immunopositive germinal
      center lymphocytes were replaced by CPP32-negative tumor cells. In contrast, the
      large cell component of follicular mixed cells (FMs) and follicular large cell
      lymphomas (FLCLs) was strongly CPP32 immunopositive in 12 of 17 (71%) and in 8 of
      14 (57%) cases, respectively, whereas the residual small-cleaved cells were
      poorly stained for CPP32 in all FLCLs and in 12 of 17 (71%) FMs, suggesting that
      an upregulation of CPP32 immunoreactivity occurred during progression. Similarly,
      cytosolic immunostaining for CPP32 was present in 10 of 12 (83%) diffuse large
      cell lymphomas (DLCLs) and 2 of 3 diffuse mixed B-cell lymphomas (DMs).
      Immunopositivity for CPP32 was also found in the majority of other types of non
      Hodgkin's lymphomas studied. Plasmacytomas were CPP32 immunonegative in 4 of 12
      (33%) cases, in contrast to normal plasma cells, which uniformly contained
      intense CPP32 immunoreactivity, implying downregulation of CPP32 in a subset of
      these malignancies. All 12 peripheral blood B-cell chronic lymphocyte leukemia
      specimens examined were CPP32 immunopositive, whereas 3 of 3 small lymphocytic
      lymphomas were CPP32 negative, suggesting that CPP32 expression may vary
      depending on the tissue compartment in which these neoplastic B cells reside. The
      results show dynamic regulation of CPP32 expression in normal and malignant
      lymphocytes.

PMID- 9160690
TI  - Lack of Fc-epsilon receptors on murine eosinophils: implications for the
      functional significance of elevated IgE and eosinophils in parasitic infections.
AB  - Chronic infection with Schistosoma mansoni induces in humans and mice a Th2
      dominant immune response in which eosinophils and IgE are conspicuously elevated.
      Human eosinophils express IgE receptors that participate in an IgE-dependent
      eosinophil-mediated ADCC reaction against Schistosomula larvae in vitro. To
      investigate the expression of IgE receptors on murine eosinophils, they were
      purified (>95% pure by Giemsa-stained cytospin preparations) from liver
      granulomas of Schistosoma-infected mice. Flow cytometric analysis showed the
      absence of the low-affinity IgE receptor Fc-epsilon RII (CD23) and Mac-2 and the
      absence of binding of murine IgE. Reverse transcription-polymerase chain reaction
      (RT-PCR) analysis of granuloma eosinophil mRNA did not detect transcripts for Fc
      epsilon RII or the alpha-chain of the high-affinity IgE receptor Fc-epsilon RI,
      but did detect transcripts that encode Mac-2 and the low-affinity IgG receptors
      Fc-gamma RIIb2, Fc-gamma RIII, and the FcR-associated gamma-chain. In vitro
      stimulation of granuloma eosinophils with interleukin-4 (IL-4) did not induce IgE
      binding, surface expression of Mac-2, or the transcription of Fc-epsilon
      receptors (Fc-epsilon RI, Fc-epsilon RII/CD23). To investigate normal murine
      eosinophils, we cultured normal mouse bone marrow cells with recombinant IL-3,
      recombinant IL-5, and recombinant granulocyte-macrophage colony-stimulating
      factor, conditions that promote eosinophil differentiation. Flow cytometric
      analysis of bone marrow-derived eosinophils failed to detect IgE binding or cell
      surface expression of Fc-epsilon RII and Mac-2, and RT-PCR analysis of
      fluorescence-activated cell sorted bone marrow-derived eosinophils failed to
      detect transcripts that encode Fc-epsilon RI or Fc-epsilon RII. These findings
      show that, in contrast to human eosinophils, murine eosinophils do not express
      cell surface receptors that bind IgE. However, because IgG receptors (Fc-gamma
      RIIb2, Fc-gamma RII) were present on eosinophils purified from granulomas, we
      investigated whether they might be involved in eosinophil activation. We found
      that an oxidative burst in eosinophils could be triggered through their IgG
      receptors.

PMID- 9160691
TI  - Neutrophils can adhere via alpha4beta1-integrin under flow conditions.
AB  - In this study we investigated the possibility that an alternative pathway exists
      for neutrophil recruitment, namely an alpha4beta1-dependent pathway. A parallel
      plate chamber was used to investigate whether neutrophils could tether, roll, and
      adhere to tumor necrosis factor alpha (TNF alpha)-stimulated endothelium via
      alpha4beta1. alpha4beta1-integrin was induced on neutrophils using
      dihydrocytochalasin B and either an endogenous (endothelial-derived) chemotactic
      agent or an exogenous chemotactic molecule. alpha4beta1-expressing neutrophils
      could stably adhere under shear force (2 dyne/cm2) to TNF alpha-stimulated
      endothelium independent of the beta2-integrin. The firm adhesion was entirely
      abolished by antibodies directed against either the alpha4 or beta1-integrin
      subunits. However, the rolling interaction was not dependent on alpha4beta1 but
      was abolished by antiselectin therapy. Neutrophils expressing alpha4beta1 could
      also tether to the endothelium in the presence of antiselectin therapy, but at
      shear stresses less than 2 dyne/cm2. alpha4beta1-expressing neutrophils also
      tethered to and stably adhered (no rolling) to VCAM-1- but not to ICAM-1
      transfected L cells. The interaction only occurred at shear stress less than 2
      dyne/cm2. A cell line (Ramos) known to express high quantities of alpha4beta1
      integrin interacted with VCAM-1-transfected L cells at very similar shear
      conditions. alpha4beta1-expressing neutrophils were also able to adhere to a
      second alpha4-integrin ligand, fibronectin; however, this interaction only
      occurred under static conditions. These data suggest that, under certain
      conditions, neutrophils can adhere independently of the beta2-integrin pathway
      and adhere via the alpha4beta1-integrin. This study refutes the concept that
      alpha4beta1-integrin adhesion is restricted to mononuclear leukocytes and is not
      functional on human neutrophils.

PMID- 9160692
TI  - Molecular characterization of PK-LR gene in pyruvate kinase-deficient Italian
      patients.
AB  - We studied the PK-LR gene in 15 unrelated Italian patients with congenital
      hemolytic anemia associated with erythrocyte pyruvate kinase (PK) deficiency.
      Fourteen different mutations were detected among 26 mutated alleles identified: a
      five-nucleotide (nt) deletion (227 to 231), two splice-site (1269C and IVS3(
      2)c), 10 missense (514C, 787T, 823A, 993A, 994A, 1168A, 1456T, 1529A, 1552A, and
      1594T) and one nonsense mutation(s) (721T). Eight of these (deletion 227-231,
      1269C, IVS3(-2)c, 514C, 787T, 823A, 1168A, and 1552A) were novel. Moreover, a new
      polymorphic site was detected in the 3' untranslated region of the mRNA (C/T,
      nucleotide 1738). The deletion 227-231 causes a stop codon after amino acid 77,
      probably resulting in an unstable gene product. Mutations 1269C and IVS3(-2)c
      lead to an alteration of the 5' and 3' splice-site consensus sequence,
      respectively; cDNA analysis failed to reveal any abnormal transcript, suggesting
      that these mutations generate an unstable mRNA that is rapidly degraded. Of the
      five new missense mutations, 823A (Gly275-Arg) and 1168A (Asp390-Asn) involve
      highly conserved amino acids, 514C (Glu172-Gln) and 1552A (Arg518-Ser), although
      found in less conserved regions, affect the balance of the electric charges of
      the protein. Mutation 787T (Gly263-Trp) is likely to determine strong
      modifications in the local structure of the molecule. The most frequent mutation
      in Italy appears to be 1456T (seven of 30 alleles), followed by 1529A (three of
      30) and 994A (three of 30). A correlation was found between mutations,
      biochemical characteristics of the enzyme, and clinical course of the disease.

PMID- 9160693
TI  - High prevalence of hepatitis G virus in bone marrow transplant recipients and
      patients treated for acute leukemia.
AB  - Hepatitis G virus (HGV) is a newly described virus that has been implicated in
      transfusion-associated hepatitis. The prevalence of HGV in a group of
      multitransfused patients with hematological malignancy was studied using a
      reverse transcription polymerase chain reaction technique. Transfusion histories
      and serum aspartate aminotransferase (AST) levels were recorded. HGV was detected
      in 29 of 60 (48%) patients. There was no difference in HGV positivity rates
      between those with normal AST levels and those with raised AST levels. Analysis
      of patients by treatment type showed that 20 of 33 (61%) patients who received a
      bone marrow transplantation procedure were HGV positive compared with 9 of 27
      (33%) treated with conventional combination chemotherapy (P = .036) despite
      similar transfusion histories. There was no significant difference in HGV
      positivity between patients treated before the introduction of United Kingdom
      blood donor screening for hepatitis C virus antibody:18 of 39 (46%) and those
      treated after the introduction of screening 11 of 21 (52%). HGV infection appears
      to be extremely common in these patients; however, the clinical significance of
      these findings with respect to liver dysfunction is not yet clear.

PMID- 9160694
TI  - Successful correction of hemophagocytic lymphohistiocytosis with related or
      unrelated bone marrow transplantation.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of immune
      regulation leading to widespread lymphocytic and hemophagocytic infiltration of
      vital organs. Apparent cure has only been achieved with allogeneic bone marrow
      transplantation (BMT). This report describes 20 consecutive patients, who
      underwent either matched sibling donor (n = 4) or unrelated donor (URD; n = 16)
      BMT. Age at the time of BMT was 0.4 to 5.3 years (median, 0.8 years). Central
      nervous system disease was present at diagnosis in 13 patients. At BMT, 14
      patients were in a clinical remission, whereas 6 patients had active HLH. All
      patients were engrafted after cytoreduction with busulfan, cyclophosphamide, and
      etoposide. The probability of grade II-III acute graft-versus-host disease (GVHD)
      for all patients was 57% (95% confidence limit [CL], 0.28, 0.86), and 73% (95%
      CL, 0.44, 1.0) in URD patients. The overall probability of survival at 3 years
      was 45% (95% CL, 0.23, 0.67) and 44% (95% CL, 0.19, 0.68) when URD BMT was
      evaluated separately. Favorable BMT outcome was associated with clinical
      remission status at the time of BMT. The preparative regimen was well tolerated,
      and in the 9 surviving patients it provided durable engraftment and was effective
      at eradicating the underlying disease.

PMID- 9160695
TI  - Use of partially mismatched related donors extends access to allogeneic marrow
      transplant.
AB  - Most patients requiring allogeneic bone marrow transplant (allo-BMT) do not have
      an HLA-matched sibling donor. A phenotypically matched unrelated donor graft has
      been made available for approximately 50% of Caucasians and less than 10% of
      ethnic and racial minorities in need. However, almost all patients have a readily
      available partially mismatched related donor (PMRD). We summarize our experience
      with 72 patients who ranged from 1 to 50 years of age (median, 16 years) and who
      were recipients of a PMRD allo-BMT from haploidentical family members following
      conditioning therapy using total body irradiation (TBI) and multiagent, high-dose
      chemotherapy. T-cell depletion and post-BMT immunosuppression were combined for
      graft-versus-host disease (GVHD) prophylaxis. The probability of engraftment was
      0.88 at 32 days. Six of 10 patients who failed to engraft achieved engraftment
      after secondary transplant. Grade II to IV acute GVHD was seen in 9 of 58 (16%)
      evaluable patients; extensive chronic GVHD was seen in 4 of 48 (8%) evaluable
      patients. There was a statistically significant difference in 2-year survival
      probability between low-risk and high-risk patients (0.55 v 0.27, P = .048).
      Prognostic factors that affected outcomes in multivariate analysis were (1) a
      lower TBI dose and 3-antigen rejection mismatch decreased stable engraftment (P =
      .005 and P = .002, respectively); (2) a higher T-cell dose increased acute GVHD
      (P = .058); (3) a higher TBI dose increased chronic GVHD (P = .016); and (4) a
      high-risk disease category increased treatment failure from relapse or death (P =
      .037). A PMRD transplant can be performed with acceptable rates of graft failure
      and GVHD. Using sequential immunomodulation, the disease status at the time of
      transplant is the only prognostic factor significantly associated with long-term
      successful outcome after PMRD allo-BMT. When allogeneic rather than autologous
      BMT is indicated, progression in disease status before transplant can be avoided
      using a PMRD with equal inclusion of all ethnic or racial groups.

PMID- 9160696
TI  - Cytomegalovirus-specific T-cell immunity in recipients of autologous peripheral
      blood stem cell or bone marrow transplants.
AB  - The cytomegalovirus (CMV)-specific CD8+ cytotoxic T-lymphocyte (CTL) and CD4+ T
      helper cell (Th) functions were characterized in 15 CMV seropositive recipients
      of autologous peripheral blood stem cell or bone marrow transplants. These immune
      functions were evaluated in peripheral blood specimens obtained before and at 1,
      2, and 3 months after transplant. For study of CTL activity, blood mononuclear
      cells were cocultured with CMV-infected autologous fibroblasts for 2 weeks and
      then tested for cytotoxicity against CMV-infected or mock-infected autologous and
      HLA-mismatched fibroblasts. The Th response to CMV antigen was assessed by
      standard lymphoproliferative assay. CMV-specific CD8+ CTL and CD4+ Th responses
      were detectable in 12 (80%) and 14 (93%) patients, respectively, in the first 3
      months after transplantation. A Th response to CMV was always present by the time
      of first CTL detection. During the posttransplant period, CMV infection occurred
      in 6 (40%) patients, and detection of CMV-specific CD8+ CTL activity was
      associated with protection from subsequent CMV infection (P = .002). Among CMV
      seropositive autograft recipients, CMV-specific CD8+ CTL and CD4+ Th responses
      are restored in a large proportion of patients in the first 3 months after
      transplantation, and the presence of a specific CD8+ CTL activity affords
      protection from CMV infection.

PMID- 9160697
TI  - Cyclosporine or cyclosporine plus methylprednisolone for prophylaxis of graft
      versus-host disease: a prospective, randomized trial.
AB  - Patients with a lymphohematopoietic malignancy considered to be at high risk for
      posttransplant relapse were enrolled in a study to compare the use of
      cyclosporine (CSP) as a single agent with a combination of methylprednisolone
      (MP) and CSP for graft-versus-host disease (GVHD) prophylaxis after marrow
      transplantation from an HLA-identical sibling donor. Sixty patients were
      randomized to receive CSP only and 62 were randomized to receive CSP plus MP.
      Daily CSP was started on day -1 (5 mg/kg/d intravenously) and administered at
      gradually reduced doses until day 180. MP was started on day 7 at 0.5 mg/kg/d,
      increased to 1.0 mg/kg/d on day 15, started on a taper schedule on day 29, and
      discontinued on day 72. All 104 evaluable patients (surviving > or =28 days) had
      sustained engraftment. The incidence rates of grades II-IV acute GVHD were 73%
      and 60% for patients receiving CSP and CSP plus MP, respectively (P = .01). No
      difference was seen for grades III-IV GVHD. However, chronic GVHD occurred
      somewhat more frequently in patients receiving CSP plus MP (44%) than in patients
      receiving only CSP (21%; P = .02). The incidence of de novo chronic GVHD was
      marginally higher in patients receiving CSP plus MP (P = .08). No significant
      differences in the risk of infections were observed. There was a suggestion that
      the risk of relapse was lower in patients receiving CSP plus MP (P = .10) and,
      although the overall survival in the two groups was not different (P = .44),
      there was a slight advantage in favor of CSP plus MP-treated patients for relapse
      free survival (P = .07). These results suggest that prophylactic MP, when
      combined with CSP, has only limited efficacy in acute GVHD prevention and may
      increase the probability of chronic GVHD.

PMID- 9160698
TI  - A novel beta+-thalassemia mutation (codon 10 GCC --> GCA) and a rare
      transcriptional mutation (-28A --> G) in Indians.

PMID- 9160699
TI  - Relationship between BCR/ABL fusion proteins and leukemia phenotype.

PMID- 9160700
TI  - Long-term follow-up of allogeneic marrow transplants in patients with aplastic
      anemia conditioned by cyclophosphamide combined with antithymocyte globulin.

PMID- 9160701
TI  - Improved reconstitution of CD4 T cells and B cells but worsened reconstitution of
      serum IgG levels after allogeneic transplantation of blood stem cells instead of
      marrow.

PMID- 9160702
TI  - Activation of the contact system in patients with sepsis and with septic shock.

PMID- 9160703
TI  - Neurons from fetal rat brains contain functional luteinizing hormone/chorionic
      gonadotropin receptors.
AB  - Adult and neonatal rat brains contain functional LH/hCG receptors. These findings
      have led us to hypothesize that the fetal rat brain may also contain these
      receptors. To test this hypothesis, we isolated neurons from 19-day-old fetal rat
      brains and cultured them in chemically defined serum-free medium. The reverse
      transcription polymerase chain reaction amplified an expected 256-base pair size
      LH/hCG receptor fragment that could hybridize with a full-length LH/hCG receptor
      cDNA in Southern blotting. Northern blotting demonstrated that neurons contained
      a major 2.6 kilobase (kb) and a minor 4.3 kb transcript. Immunocytochemistry
      demonstrated that the neurons contained LH/hCG receptor immunostaining. Western
      immunoblotting showed that neurons contained an 80-kDa receptor protein that
      increased to a maximal level on Day 3 of culture and then gradually decreased
      until the 9th day of culture. Culturing neurons for 3 days in the presence of
      highly purified hCG resulted in a dose-dependent increase in the outgrowth of
      neurite processes and total cellular protein and a decrease in DNA fragmentation
      as compared to values in the corresponding controls. At the maximally effective
      hCG concentration, the number of neurite-bearing cells was increased by 53% and
      the total cellular protein by 60%, and DNA fragmentation decreased by 31%. In
      summary, this is the first study to demonstrate the presence of LH/hCG receptors
      and neurotrophic effects of hCG in fetal rat brain neurons. These findings imply
      that locally produced gonadotropins may possibly play a role in the growth and
      development of the fetal brain.

PMID- 9160704
TI  - Localization of steroidogenic enzymes in macaque luteal tissue during the
      menstrual cycle and simulated early pregnancy: immunohistochemical evidence
      supporting the two-cell model for estrogen production in the primate corpus
      luteum.
AB  - It is hypothesized that the two-cell model for estrogen production by the ovarian
      follicle is preserved in the primate corpus luteum, but there is little direct
      evidence to support this theory. To determine the sites of androgen and estrogen
      synthesis within the primate corpus luteum and to ascertain whether changes in
      steroid hormone levels are related to steroidogenic enzyme expression, the
      enzymes converting progesterone to androgen (cytochrome P450 17alpha
      hydroxylase/17,20 lyase; P450(c17)) and then to estrogen (aromatase; P450(arom)),
      as well as P450 side-chain cleavage (P450(scc)) and 3beta-hydroxysteroid
      dehydrogenase (3beta HSD), were detected by immunohistochemistry in macaque
      luteal tissue throughout the menstrual cycle and simulated early pregnancy.
      Corpora lutea were collected from rhesus monkeys in the early (Days 2-4 post-LH
      surge), mid (Days 6-8), mid-late (Days 10-12), and late (Days 14-15) luteal phase
      and after 1, 3, 6, or 9 days of hCG treatment that began on Day 9 of the luteal
      phase. Specific cytoplasmic staining for P450(c17), P450(arom), P450(scc), and
      3beta HSD was present in luteal cells, but not in the microvasculature, within
      all luteal tissues examined. P450(c17)-stained luteal cells were located along
      the vascular tracts and around the periphery of the corpus luteum. Intensely
      stained luteal cells were associated with blood vessels entering from the outer
      surface of the corpus luteum, but not with blood vessels returning from the
      connective tissue centrum. In contrast, P450(arom)-stained luteal cells were
      distributed throughout the luteal parenchyma. P450(c17) staining intensity was
      similar at all stages of the luteal phase; however, the number and intensity of
      P450(arom)-stained cells decreased by late luteal phase. In simulated early
      pregnancy, cells stained for P450(c17) were present near blood vessels, with some
      positive cells scattered throughout the corpus luteum. P450(arom) immunostaining
      was heterogeneous within the corpus luteum; many intensely stained cells were
      interspersed among others that were only lightly stained. Overall, cellular
      staining for P450(c17) and P450(arom) remained intense through 9 days of
      simulated early pregnancy. In contrast, P450(scc) and 3beta HSD immunoreactivity
      were not located in distinct luteal compartments. These results are consistent
      with a two-cell model for steroid hormone production in the primate corpus
      luteum, whereby paraluteal (theca-luteal) cells produce androgen substrate that
      is converted to estrogens by true (granulosa-) luteal cells. The divergence in
      enzyme detection as the luteal phase progresses, with P450(c17) labeling high and
      P450(arom) staining having decreased, suggests a shift in the function of the
      corpus luteum as it ages. Enzyme localization during chorionic gonadotropin
      exposure simulating early pregnancy demonstrates the continued capacity of the
      primate corpus luteum to produce steroid hormones.

PMID- 9160705
TI  - Apoptosis during mouse blastocyst formation: evidence for a role for survival
      factors including transforming growth factor alpha.
AB  - Mouse blastocysts undergo cell death in the inner cell mass (ICM) as a normal
      feature of development, but little is known as to how this event is regulated or
      as to the possible role of survival factors in preimplantation development. The
      observation that growth factors, which can influence preimplantation development,
      can act as survival factors in other cell types led us to investigate the effects
      of culture in vitro, embryo density during culture, and transforming growth
      factor alpha (TGF alpha) on cell death in the blastocyst. Mouse blastocysts
      cultured singly from the 2-cell stage in 25 microl of medium KSOM + amino acids
      showed a approximately 3-fold increase in the incidence of cell death,
      predominantly in the ICM, relative to blastocysts formed in vivo. Increasing the
      density of embryo culture to 30 embryos per 25 microl of culture medium
      accelerated development, increased final blastocyst cell number, and partially
      (approximately 50%) reduced the increase in cell death induced by culture in
      vitro. Addition of 0.1 pM TGF alpha to the medium of singly cultured embryos also
      partially (33%) reduced this increase in cell death without accelerating
      development or increasing final cell number. Culturing isolated ICMs for 24 h in
      the presence of 0.1 pM TGF alpha also partially (33%) reduced the increase in
      cell death. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling
      of whole blastocysts confirmed that cell death as detected by fragmented nuclei
      was apoptotic, as defined by endonuclease activation. Results of these
      experiments suggest that endogenously produced growth factors may function as
      cell survival factors during preimplantation development.

PMID- 9160707
TI  - Follicle-stimulating hormone (FSH) regulates the expression of FSH receptor
      messenger ribonucleic acid in cultured Sertoli cells and in hypophysectomized rat
      testis.
AB  - FSH acts on Sertoli cells via interaction with a transmembrane receptor (FSHr).
      Control of expression of the receptor is surely a factor in the regulation of the
      action of FSH. The regulation of FSHr by FSH and testosterone was studied both in
      culture and in vivo. Sertoli cells from 18- to 20-day-old male rats were cultured
      in the presence of 25 ng/ml ovine (o) FSH. At 8 h after addition of FSH,
      expression of FSHr mRNA decreased significantly. Addition of FSH and actinomycin
      D to cells did not result in a further decrease in FSHr mRNA levels, suggesting
      that FSH does not alter turnover of FSHr mRNA. Treatment of cells with 40 ng/ml
      testosterone did not have any significant effect on the expression of FSHr mRNA.
      Hypophysectomy of 20-day-old male rats resulted in an increase in expression of
      FSHr mRNA as compared to that in sham-hypophysectomized animals. This increase
      was measured at 24 h posthypophysectomy and was maintained at 72 h after surgery.
      Injection of rats with 0.2 U oFSH at 48 h posthypophysectomy resulted in a
      reduction in FSHr mRNA when compared to the levels in hypophysectomized rats.
      Treatment with 2 mg testosterone propionate had no effect on FSHr mRNA levels.
      The findings confirm that FSH plays an important role in regulating mRNA
      expression of the FSHr in Sertoli cells in culture and show for the first time
      that FSHr mRNA is regulated in vivo by FSH in the immature rat testis.

PMID- 9160706
TI  - Abnormal uterine stromal and glandular function associated with maternal
      reproductive defects in Hoxa-11 null mice.
AB  - Here we describe in detail both the expression of Hoxa-11 in the wild-type mouse
      uterus and the defects resulting in maternal reproductive failure of Hoxa-11 null
      female mice. The Hoxa-11 gene is expressed at peak levels in uterine stromal
      cells during metestrus. Hoxa-11 transcripts were induced beginning on Day 2 of
      gestation in the stromal cells underlying the uterine epithelium and appeared in
      the secondary decidual zone between Days 6 and 8 of gestation. At early
      gestational stages, stromal, decidual, and glandular cell development were
      deficient in Hoxa-11 null uteri in comparison to wild-type as assessed by
      histology and immunohistochemical localization of the decidual cell marker
      epitope, stage-specific embryonic antigen-3 (SSEA-3). Both steroid-induced
      uterine stromal and glandular cell proliferation as well as oil-induced stromal
      decidualization after induction of pseudopregnancy were deficient in mutant
      uteri. Moreover, both Western blotting and immunohistochemistry demonstrated that
      the burst of glandular leukemia inhibitory factor (LIF) found in normal pregnant
      uteri at Day 4.5 of gestation was absent in Hoxa-11-deficient uteri. The LIF
      burst was also not observed in the uteri of bilaterally ovariectomized,
      hormonally stimulated Hoxa-11 mutants. These results demonstrate that the Hoxa-11
      gene is required for normal uterine stromal cell and glandular differentiation
      during pregnancy, as is the presence of the steroid-induced glandular LIF burst
      initiating embryo implantation.

PMID- 9160708
TI  - Comparative study of uterine morphogenesis and protein secretion in neonatal
      White crossbred and Meishan gilts.
AB  - Thirty-five crossbred and 22 Meishan contemporary gilts were necropsied on Day 1,
      14, 28, 42, or 56 of age (birth = Day 0). At necropsy, a cross section of one
      uterine horn was fixed for histomorphometric study, and minced uterine tissue was
      cultured with 50 muCi [3H]leucine. Secreted proteins were identified by two
      dimensional PAGE, fluorography, and incorporation of radioactivity. Body weights
      at necropsy were similar for the two breeds and increased (p < 0.01) between Days
      1 and 56 of age. Ovarian and uterine weights, as well as histomorphometric areas,
      were similar for the two breeds on Day 1 but increased markedly (p < 0.01) in
      Meishan gilts on Day 56. In gilts of both breeds, secretion of uterine proteins 1
      (M(r) x 10(-3)/pI; 45/6.0), 2a and 2b (doublet, 25/6.2), and 3 (20/5.5) increased
      in association with endometrial gland development. A fourth protein (97/4.0) was
      observed in gilts of both breeds but was more abundant in Meishan; a fifth
      protein (13/6.0) was detected only in crossbred gilts on Day 56. Although
      specific regulatory roles for locally produced uterine proteins remain to be
      defined, the increase in specific uterine proteins and breed differences in
      uterine protein secretion suggest that uterine proteins may influence early
      uterine development.

PMID- 9160709
TI  - Telomerase activity in female and male rat germ cells undergoing meiosis and in
      early embryos.
AB  - Telomerase is a ribonucleoprotein that synthesizes telomeric DNA at the ends of
      eukaryotic chromosomes. It has been hypothesized that telomerase activity is
      necessary for cellular immortalization and that telomerase activity is present in
      cells of germline origin. The objective of the present study was to determine the
      level of telomerase activity in the following rat cells: 1) oocytes from
      follicles at different stages of development, 2) spermatogenic cells, and 3)
      early embryos. Telomerase activity was quantitated using a recently developed,
      sensitive polymerase chain reaction-based assay and a human kidney cell line
      (293) as a standard. Telomerase activity was found in oocytes from early antral
      and preovulatory follicles, as well as in ovulated oocytes. The level of enzyme
      activity in early antral and preovulatory follicles was comparable to that of the
      293 cells, while levels in ovulated oocytes were 50-fold lower. Telomerase
      activity was present in even lower levels in pachytene spermatocytes and round
      spermatids, and no telomerase activity was detected in spermatozoa from either
      the caput or the cauda epididymis. After fertilization, telomerase activity was
      present in 4-cell embryos. Telomerase activity was also detected in several rat
      somatic tissues. These data demonstrate that telomerase activity is present in
      germ cells at several stages of differentiation, with the exception of
      spermatozoa, and suggest that telomerase activity may be important during
      meiosis. The high levels of telomerase activity in individual oocytes may serve
      as a marker for monitoring the effects of hormonal agents, aging, and toxins on
      oocyte quality.

PMID- 9160710
TI  - Characterization of insulin and insulin-like growth factor-I ovarian receptors
      during the reproductive cycle of carp (Cyprinus carpio).
AB  - Insulin and insulin-like growth factor-I (IGF-I) receptors were characterized in
      glycoprotein fractions prepared by wheat germ agglutinin-agarose affinity
      chromatography from the ovaries of carp. Insulin-specific overall binding in carp
      ovaries was 6- to 11-fold lower than IGF-I binding (2.7 +/- 0.48% vs. 22.8 +/-
      3.6% per 20 microg glycoprotein). Cold IGF-I displaced radiolabeled IGF-I binding
      in doses 1000- to 3000-fold lower than cold insulin. On the other hand, cold
      insulin displaced radiolabeled insulin binding at concentrations 5- to 30-fold
      lower than cold IGF-I. The alpha-subunit molecular masses of carp insulin and IGF
      I receptors were smaller than the alpha-subunit molecular mass of rat insulin
      receptor (125 and 120 vs. 135 kDa, respectively). Autophosphorylation of carp
      beta-subunit insulin and IGF-I receptors showed similar molecular masses that did
      not differ from the molecular mass of rat insulin beta subunit. Receptor tyrosine
      kinase activity was stimulated in a dose-dependent manner by insulin and IGF-I.
      Insulin and IGF-I stimulated tyrosine kinase activity and reached a maximum,
      respectively, of 224 +/- 14% and 279 +/- 7% of basal phosphorylation. Insulin and
      IGF-I binding characteristics were measured through different stages of
      follicular development. High specific binding of both peptides in primary oocyte
      growth (5.6 +/- 0.8% and 50 +/- 10% per 20 microg glycoprotein for insulin and
      IGF-I, respectively) decreased to a minimum at the end of vitellogenesis,
      followed by a slight increase later, in the preovulatory stage. The presence of
      insulin and IGF-I receptors in carp ovaries and the changes in percentage of
      binding throughout the reproductive cycle suggest that, in carp, the roles of
      insulin and IGF-I depend on the ovarian maturation stage.

PMID- 9160711
TI  - Mechanism of infertility in male guinea pigs immunized with sperm PH-20.
AB  - PH-20, a testis-specific protein first expressed in haploid germ cells, is
      present on the posterior head plasma membrane and inner acrosomal membrane of
      mature guinea pig sperm. PH-20 is bifunctional, having a hyaluronidase activity
      that allows sperm to penetrate the cumulus layer and a separate activity required
      for binding of acrosome-reacted sperm to the zona pellucida. The immunization of
      male guinea pigs with PH-20 reproducibly results in infertility with a duration
      of 6-12 mo or longer. In this study, we analyzed the immunopathology in the
      reproductive tract of PH-20-immunized males to probe the mechanism(s) responsible
      for the induced infertility and found two separate effects. Remarkably, in almost
      all infertile, PH-20-immunized males, the caudae epididymides were empty
      (contained no sperm) or contained only abnormal sperm. The complete loss of
      normal sperm in the epididymis apparently results in infertility. A second effect
      was the induction of experimental autoimmune orchitis (EAO), representing the
      first report of EAO induced by a purified testis/sperm molecule of known
      functions. PH-20-induced EAO differed from EAO induced by crude testis antigens
      in two respects: 1) an absence of epididymitis with abscess and granuloma and 2)
      the presence of antibody on germ cells within seminiferous tubules and inside the
      cauda epididymidis. The former suggests that crude testis antigens other than PH
      20 are responsible for epididymitis, and the latter suggests a possible role of
      antibody in EAO pathogenesis and infertility induction. Return to fertility,
      after 6-12 mo, was accompanied by regression of EAO and reappearance of
      spermatozoa in the caudae epididymides.

PMID- 9160712
TI  - Reversible contraceptive effect of PH-20 immunization in male guinea pigs.
AB  - Sperm proteins are currently being studied as antigens on which to base a
      contraceptive vaccine. Sperm plasma membrane proteins offer the theoretical
      possibility of immunizing either males or females and achieving a contraceptive
      effect. In this study, we investigated the sperm plasma membrane protein PH-20 as
      an antigen for inducing infertility in males. We found that infertility can
      reproducibly be induced in male guinea pigs immunized with purified PH-20: 100%
      (29 of 29) of PH-20-immunized males became infertile, whereas all 22 controls
      were fertile. The males were extremely responsive to PH-20 immunization:
      infertility could be induced with a single injection of only 5 microg PH-20.
      Among males that received their initial injection when they were approximately
      300 g (body weight), 14 of 15 had regained fertility at about 1 yr after initial
      injection. Surprisingly, in another group of males that received their first
      injection when they were approximately 650 g (body weight), only 1 of 5 had
      regained fertility about 1 yr after initial injection. Anti-PH-20 titers in
      antisera (2 mo after initial injection) were generally in the range 1.1-4.2 x
      10(4) in twice-injected males and the range 1.8-9.4 x 10(3) in once-injected
      males. Over the next 6-11 mo, twice-injected males' titers decreased > or = 4
      fold, whereas once-injected males' titers decreased slightly (1.1 - to 1.8-fold).
      After 6-11 mo, anti-PH-20 titers were in the range 1.0-4.8 x 10(3), and the
      precise residual titer did not correlate with fertility/infertility. The results
      show that immunization of males with PH-20, even at low doses, results in a
      reproducible, completely effective contraceptive action.

PMID- 9160713
TI  - Ontogeny of lactoferrin in the developing mouse uterus: a marker of early hormone
      response.
AB  - Lactoferrin (LF) was mapped during organogenesis of the murine reproductive
      tract, starting on fetal Day 12, as a marker of estrogen responsiveness. To
      induce LF expression, pregnant outbred CD-1 mice were injected s.c. with
      diethylstilbestrol (DES; 100 microg/kg maternal body weight), and fetal genital
      tract tissues were removed; neonatal and immature mice received s.c. injections
      of DES (2 microg/pup per day). Corn oil-treated and untreated mice at
      corresponding ages provided the controls. Immunocytochemical techniques using a
      polyclonal antibody showed no detectable LF in control genital tract tissues
      until late gestation. However, after DES treatment, LF was localized in uterine
      epithelial cells as early as fetal Day 14; the intensity of LF staining increased
      with age and number of DES treatments. Control uterine tissues responded to the
      rise of circulating estrogens at parturition (fetal Day 19) by producing LF,
      although the magnitude of response was lower than that of DES-treated tissues.
      Uterine tissue homogenates from control and DES mice were analyzed by SDS-PAGE
      and Western blots, verifying the protein to be LF. Isolation of mRNA and Northern
      blot analysis further showed that LF mRNA was present in the developing Mullerian
      duct and that DES stimulated early induction of the LF gene. The early appearance
      of LF suggests that it may play an important role in the hormonal regulation of
      growth and differentiation of developing uterine tissues.

PMID- 9160714
TI  - Changes in messenger ribonucleic acid encoding luteinizing hormone receptor,
      cytochrome P450-side chain cleavage, and aromatase are associated with
      recruitment and selection of bovine ovarian follicles.
AB  - The objective of this study was to investigate changes in expression of mRNAs
      encoding FSH receptor (FSHr), LH receptor (LHr), cytochrome P450 side-chain
      cleavage (P450(scc)), cytochrome P450 17alpha-hydroxylase (P450(c17)), and
      cytochrome P450 aromatase (P450(arom)) during recruitment and selection of bovine
      ovarian follicles. Dairy heifers (4-5 per group) were ovariectomized at 12, 24,
      36, 48, 60, 72, 84, or 96 h after initiation of the first follicular wave
      following estrus as determined by ultrasonography (Time 0 = initiation of
      follicular wave; mean +/- SEM = 42.0 +/- 2.6 h after estrus). Expression of mRNAs
      encoding FSHr, LHr, P450(scc), P450(c17), and P450(arom) was detected by in situ
      hybridization and quantified by image analysis. Antral follicles were classified
      as healthy or atretic. Healthy follicles expressed higher (p < 0.01) amounts of
      mRNAs for gonadotropin receptors and steroidogenic enzymes than did atretic
      follicles, and expression of LHr, FSHr, P450(scc), P450(c17), and P450(arom)
      increased (p < 0.01) with follicular size and stage of the follicular wave.
      Expression of mRNAs for P450(scc), P450(arom), and LHr was time- and size
      dependent during recruitment and selection. During recruitment, expression of
      mRNAs for P450(scc) and P450(arom) was first detected in granulosa cells of 16 of
      21 of the follicles 4-6 mm in diameter at 12 h. At 24 and 36 h, almost all
      follicles 6-9 mm in diameter, but not those 4-5 mm in diameter, expressed both
      P450(scc) and P450(arom) mRNA in the granulosa cells. At 48 h and thereafter,
      P450(scc) and P450(arom) mRNA were expressed predominantly in one healthy large
      follicle per cow with a few exceptions. Expression of LHr mRNA was first detected
      in granulosa cells at 36 h and was always found in granulosa cells of one
      follicle > or = 8 mm per cow with exception of one cow at 36 h (no expression)
      and another two cows, one each at 36 and at 84 h (expression in 2 follicles). In
      addition, LHr mRNA expression in the granulosa cell layer was limited to
      follicles that also expressed mRNAs for P450(scc) and P450(arom) in the granulosa
      cells. In summary, follicular recruitment in cattle was associated with
      expression of P450(scc) and P450(arom) mRNA within granulosa cells, and the
      process of follicular selection was associated with initiation of LHr mRNA
      expression in granulosa cells.

PMID- 9160715
TI  - Control of human sperm intracellular pH by cholesterol and its relationship to
      the response of the acrosome to progesterone.
AB  - When incubated in vitro, human sperm gradually become capable of acrosome
      reacting in response to the agonist progesterone. Loss of unesterified
      cholesterol is required for sperm to become responsive to progesterone, but how
      cholesterol regulates acrosomal responsiveness is unknown. These experiments
      tested the hypothesis that loss of sperm cholesterol leads to a rise in the
      intracellular pH (pH(i)) that makes the sperm responsive to progesterone. pH(i)
      was measured using BCECF (2',7'-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein) in
      freshly ejaculated sperm (T0 sperm) and in sperm incubated in vitro overnight
      (T24 sperm). During incubation, pH(i) increased from 6.94 +/- 0.03 to 7.08 +/-
      0.01 (mean +/- SEM, n = 4, p < 0.01). Incubating sperm 24 h in medium
      supplemented with 1 microM cholesterol to prevent loss of sperm cholesterol
      suppressed the rise of pH(i) (T24C sperm, pH(i) = 6.96 +/- 0.03, n = 4, p = 0.64
      compared to T0 sperm). To test whether their lower pH(i) prevents T24C sperm from
      reacting, we treated T24C sperm with the alkalinizing agents trimethylamine
      chloride (TMA) or NH4Cl. These agents did cause T24C sperm to respond to
      progesterone in a dose-dependent fashion, but they also caused a similar increase
      in the number of reacting T24 sperm. These agents probably do not reverse the
      inhibiting effects of high cholesterol but rather make responsive a subpopulation
      of sperm that is present regardless of the cholesterol content. NH4Cl and TMA did
      not make T0 sperm responsive to progesterone. The acidifying agent sodium
      propionate did not diminish the response of T24 sperm to progesterone. In
      summary, pH(i) increases during incubation in vitro in a cholesterol-dependent
      fashion. Elevated pH(i) alone is probably not sufficient to make sperm
      acrosomally responsive.

PMID- 9160716
TI  - Estrogen withdrawal induces macrophage invasion in the rabbit corpus luteum.
AB  - Macrophages within the corpus luteum are associated with spontaneous luteal
      regression in a number of species. However, an understanding of the consequences
      of macrophage recruitment on the functional capacity and responsiveness of the
      luteal tissue has remained elusive. Here we investigate the temporal appearance
      of macrophages and their potential impact in corpora lutea of rabbits, in which a
      rapid fall in progesterone synthesis and premature regression of the corpus
      luteum are initiated by withdrawal of the luteotropic hormone estradiol-17beta.
      Removal of estradiol implants, placed subcutaneously, induced a significant
      increase in the average number of macrophages per high-power field (hpf) in
      corpora lutea (p < 0.05) within 72 h. Replacement of the estradiol implants 48 h
      after their removal resulted in a marginal rebound of plasma progesterone and a
      variable number of luteal macrophages (range: 6-160 macrophages/hpf) among the 11
      rabbits. A third experiment revealed that the relative numbers of macrophages
      within the corpora lutea have no apparent relationship to rates of progesterone
      synthesis in vitro: progesterone production (ng/mg tissue) did not differ (p >
      0.05) between corpora lutea of estradiol-maintained rabbits and those of
      estradiol-replaced rabbits despite obvious differences in numbers of luteal
      macrophages (2 +/- 1 vs. 42 +/- 10 macrophages/hpf, respectively; p < 0.05). We
      conclude that the entry/recruitment of macrophages into the rabbit corpus luteum
      is sensitive to the luteotropic hormone estradiol-17beta and that the presence of
      macrophages does not preclude the continuation of progesterone production in
      surviving luteal tissue revitalized after estradiol removal/replacement.

PMID- 9160717
TI  - Assessment of the role of tissue inhibitor of metalloproteinase-1 (TIMP-1) during
      the periovulatory period in female mice lacking a functional TIMP-1 gene.
AB  - Tissue inhibitor of metalloproteinase (TIMP)-1 is a multifunctional peptide that
      has been implicated in the ovulatory process. To assess the function of TIMP-1
      during the periovulatory period in vivo, mice incapable of expressing the TIMP-1
      gene product were utilized. Twenty-three-day-old TIMP-1-deficient (n = 59) and
      wild-type (n = 61) female mice were injected with 5 IU eCG, followed 48 h later
      by an ovulation-inducing dose of hCG (5 IU). Animals were killed at the time of
      hCG injection (0-h hCG), at 12 h (12-h hCG), or at 24 h post-hCG (24-h hCG)
      administration. Serum was collected for the assessment of estradiol-17beta (0-h
      hCG groups) or progesterone content (12- and 24-h hCG groups), while ovaries were
      removed for either histological preparation or Northern analysis of TIMP-1, TIMP
      2, and TIMP-3. The number of healthy and atretic follicles was determined in the
      0-h hCG groups, as was the number of oocytes released in the 24-h hCG group. TIMP
      1-deficient females in the 0-h hCG group showed reduced levels of ovarian TIMP-2
      (0.29-fold decrease, p < 0.05) and TIMP-3 (3.0-fold decrease, p < 0.05)
      expression compared to wild-type counterparts. No significant difference was
      detected between genotypes in the 0-h hCG group for number of healthy or atretic
      follicles or for serum estradiol-17beta concentrations. Additionally, no
      significant differences were detected between genotypes in the 12- and 24-h hCG
      groups for serum progesterone concentrations, ovarian TIMP-2 and TIMP-3
      expression, or number of oocytes released (24-h hCG group). To assess the effect
      of TIMP-1 on steroidogenesis in vitro, granulosa cells were obtained from 23-day
      old, eCG-primed TIMP-1-deficient and wild-type females. Addition of recombinant
      human TIMP-1 significantly increased conditioned media estradiol-17beta
      concentrations in cell cultures from both mutant (1.32-fold over controls; p =
      0.02; n = 4) and wild-type females (1.16-fold over controls; p = 0.04; n = 3). It
      is concluded from this study that TIMP-1 may modulate ovarian TIMP-2 and TIMP-3
      mRNA expression during folliculogenesis. In addition, TIMP-1 exhibits
      steroidogenic activity in vitro, but no evidence was found for regulation of
      steroidogenesis in vivo.

PMID- 9160718
TI  - Expression of basic fibroblast growth factor, endothelial mitogenic activity, and
      angiotensin II type-1 receptors in the ovine placenta during the third trimester
      of pregnancy.
AB  - To evaluate expression of basic fibroblast growth factor (FGF), endothelial
      mitogenic activity, and angiotensin II type-1 receptors (AT1r), as well as the
      role of angiotensin II (ANG II) in regulating basic FGF production/secretion,
      placentae were obtained from ewes on Days 110, 120, 130, and 142 of pregnancy and
      were separated into fetal cotyledonary (COT) and intercotyledonary (ICOT), as
      well as maternal caruncular (CAR) and intercaruncular (ICAR) components. Using
      immunohistochemistry, basic FGF and AT1r were found for the most part to be
      colocalized in all placental components, primarily in epithelium, stroma,
      endothelium, and vascular smooth muscle. Changes in basic FGF levels in placental
      explant-conditioned media were observed in fetal, but not maternal, components.
      In COT, basic FGF levels increased 2.4-fold (r2 = 0.48, p < 0.04) from Day 110 to
      130 and then declined at term. In ICOT, basic FGF levels increased 6.4-fold (r2 =
      0.33, p < 0.05) from Day 110 to 142. The rank order of averaged basic FGF levels
      was COT > CAR > ICOT = ICAR (p < 0.05). Endothelial mitogenic activity of
      conditioned media was observed in COT from Day 130 pregnant ewes (232.5 +/- 38.7%
      of control; p < 0.05) but not in other components, and it was neutralized by a
      basic FGF antibody. ANG II did not alter basic FGF levels in any placental
      component. Thus, throughout the third trimester, 1) basic FGF and AT1r are
      present in placentae, 2) both basic FGF levels and endothelial mitogenic activity
      in COT increase, 3) basic FGF levels are associated with endothelial mitogenic
      activity of COT, and 4) ANG II has no effect on production/secretion of basic FGF
      by the placenta.

PMID- 9160719
TI  - Bovine sperm binding to oviductal epithelium involves fucose recognition.
AB  - Sperm binding to oviductal epithelium probably serves to form the isthmic sperm
      reservoir. This interaction of sperm and oviductal epithelium may involve species
      specific carbohydrate recognition. We tested a series of carbohydrates and
      glycoproteins for inhibition of bovine sperm binding to oviductal epithelium in
      vitro. Explants of isthmic and ampullar epithelium were obtained from oviducts
      that had been surgically removed from preovulatory heifers. The explants were
      incubated (39 degrees C, 5% CO2) with fetuin, asialofetuin, ovalbumin, fucoidan,
      fucose, N-acetyl glucosamine, or N-acetyl glucosamine sulfate dissolved in a
      modified Tyrode's balanced salt solution, termed sperm-TALP (pH 7.4, 295 mOsm)
      for 10 min before frozen-thawed motile sperm obtained by swim-up were added.
      After 15 min, the explants were rinsed, and sperm binding density was evaluated.
      Oviductal explants treated with fucoidan (3 mg/ml; p < 0.001, n = 5) or fucose
      (31 mM, p < 0.01, n = 6) had reduced densities of bound sperm compared to the
      controls. Incubation of explants in increasing concentrations of fucose (4-62 mM)
      resulted in increased inhibition of sperm binding. Pretreating explants with
      fucosidase also reduced sperm binding (p < 0.001, n = 3) compared to that in
      controls containing the fucosidase inhibitor deoxyfuconojirimycin. The presence
      of fucosylated molecules on the surface of the oviductal epithelium was confirmed
      by labeling with fucose lectins from Ulex europeus and Lotus tetragonolobus. We
      conclude that fucose is involved in a specific interaction between bovine sperm
      and oviductal epithelium.

PMID- 9160720
TI  - Estradiol up-regulates estrogen receptor and progesterone receptor gene
      expression in specific ovine uterine cells.
AB  - The regulation of estrogen receptor (ER) and progesterone receptor (PR) genes is
      critical to estrogen and progesterone responsiveness of the uterus during the
      estrous cycle. A low dose of estradiol, given to ovariectomized ewes to mimic the
      preovulatory estrogen surge, acutely enhanced ER and PR gene expression in most
      uterine cells. Estradiol effects were measured at 12, 24, and 48 h post-injection
      (n = 6 ewes per time) with immunohistochemistry and in situ hybridization.
      Whereas vehicle-treated ovariectomized ewes demonstrated low to moderate ER and
      PR mRNA and protein expression, estradiol enhanced PR mRNA and protein expression
      (at 12 h and 24 h, respectively) more rapidly than ER mRNA and protein expression
      (at 24 h and 48 h, respectively) in most uterine cells. However, the timing and
      extent of the estradiol response depended partly upon cell type (epithelial,
      stromal, or myometrial), cell region (luminal, superficial, middle, or deep
      endometrial or myometrial), adjacent cells, and prior progesterone treatment. For
      example, PR mRNA up-regulation was prolonged in middle and deep endometrial
      stroma, but increases in PR protein expression were highest in superficial and
      middle endometrial compartments, including the luminal epithelium. The luminal
      epithelium and myometrium were unique in that estradiol failed to up-regulate ER
      gene expression within them. ER mRNA levels rose within these compartments only
      when estradiol followed steroid hormone treatment designed to induce an
      artificial estrous cycle (estradiol-progesterone-estradiol [EPE] treatment). The
      EPE treatment also augmented the rise in ER mRNA concentrations within stromal
      cells compared to estradiol treatment alone. Within uterine cell compartments,
      subpopulations of adjacent cells showed distinct estradiol responses, e.g., very
      high levels of ER and PR gene expression within stromal cells directly underlying
      glandular epithelial cells. Because the estradiol response did not always
      correlate with initial ER protein levels and was partly dependent upon cell
      compartment and adjacent cells, we must conclude that direct transcriptional
      and/or posttranscriptional actions of estradiol cooperate with other cellular and
      paracrine regulatory factors to regulate ER and PR gene expression and, thus, the
      steroid responsiveness of uterine cells.

PMID- 9160721
TI  - Effect of dietary fat on the fatty acid composition and fertilizing ability of
      fowl semen.
AB  - Broiler breeder roosters received two diets, containing either 5% salmon oil (SO)
      or 5% corn oil (CO). The diets differed essentially in their polyunsaturated
      fatty acid (PUFA) composition, with n-6:n-3 fatty acid ratios of 41.6 in SO and
      1.5 in CO. The effects of these diets on the fatty acid composition of
      spermatozoa and seminal plasma, and on fertility evaluated after artificial
      insemination were observed. Whatever the diet, the fatty acid composition of
      spermatozoa showed notable amounts of 20:4n-6 (5-9%) and 22:4n-6 (15-21%). These
      essential fatty acids were not detected in the diets and were synthesized from
      18:2n-6, which was abundant in the diet (15-16%) but low in spermatozoa (2-3%).
      Spermatozoa were also very rich in saturated fatty acids (39%). There was a clear
      influence of dietary lipids on the spermatozoa fatty acid profile: the proportion
      of n-3 fatty acids in spermatozoa from males fed SO compared to CO was higher
      (9.6% vs. 4.3%) and that of n-6 fatty acids was lower (22.4% vs. 33.3%). The
      fatty acid composition of seminal plasma included a higher proportion of
      saturated fatty acids (49%) than the proportion in spermatozoa, whereas minor
      fatty acids (14:0, 16:1n-7, 16:1n-9, 22:5n-3) were not detected. The influence of
      dietary lipids on the seminal plasma fatty acid profile was the same as for the
      spermatozoa, especially in the PUFA profile. In addition, the SO diet gave
      significantly higher fertility rates (96%) than the CO diet (91.6%). These
      results clearly show that the lipid composition of the diet may modify the fatty
      acid composition of the semen and its fertilizing ability.

PMID- 9160722
TI  - Is nitric oxide involved in the regulation of the rat testicular vasculature?
AB  - Using immunohistochemistry, endothelial nitric oxide synthase (NOS), and neuronal
      NOS were localized in the endothelium of rat testicular arteries and in Leydig
      cells, respectively. NADPH-diaphorase activity, indicating NOS activity, however,
      was present only in endothelial cells. In order to examine the role of nitric
      oxide (NO) in the regulation of rat testicular vasculature, intact and hCG
      pretreated (50-100 IU hCG given s.c. 6 h earlier) animals were given injections
      of the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), 10 mg/kg i.v.).
      In all rats this resulted in a major increase in blood pressure. In intact,
      unstimulated animals, testicular vascular resistance was unaffected, and
      testicular blood flow consequently increased. In hCG-treated animals, in
      contrast, vascular resistance increased in an hCG dose-related way. L-NAME
      treatment also increased the hCG-induced accumulation of polymorphonuclear
      leukocytes in testicular venules. Treatment with N(G)-nitro-D-arginine methyl
      ester (D-NAME, 10 mg/kg i.v.), an inactive isomer of L-NAME, had no effect on the
      testicular vasculature. The study suggests that NO plays only a limited role in
      the regulation of testicular blood flow under basal conditions. After hCG
      treatment, however, NOS activity appears to be increased (increased endothelial
      NADPH-diaphorase staining), suggesting that NO in this situation is of importance
      to increase blood flow and to inhibit leukocyte accumulation.

PMID- 9160723
TI  - Influence of estradiol and progesterone withdrawal on the secretion of and the
      temporal correlation between pulses of oxytocin and prostaglandin F2(alpha) in
      ewes.
AB  - The primary objective was to examine the effects of estradiol and the
      progesterone receptor antagonist onapristone on the pulsatile secretion of
      prostaglandin F(2alpha) (PGF(2alpha)) and ovarian and pituitary oxytocin. A 2 x 2
      factorial arrangement of estradiol and onapristone treatments was administered to
      groups of 5 ewes after destruction of ovarian follicles on Day 8 of the cycle.
      Estradiol treatments consisted of the administration of a silicone elastomer
      implant, either containing or not containing estradiol, on Day 8 plus 50 microg
      of estradiol or corn oil on Days 11 and 12. Onapristone (2 mg/kg) or its vehicle
      were administered on Day 13, immediately preceding the simultaneous collection of
      blood samples from the carotid artery, jugular vein, and vena cava at 7.5-min
      intervals for 7 h. Ewes were immediately killed for measurements of uterine
      oxytocin receptor concentrations and phosphatidylinositide turnover. More
      oxytocin pulses were detected in the jugular vein than in the carotid artery (p <
      0.01), suggesting that the pituitary is a source of oxytocin. A similar number (p
      > 0.1) of PGF(2alpha) pulses were correlated with oxytocin pulses as were not.
      The linked PGF(2alpha) pulses were longer in duration (p = 0.01) with a tendency
      toward a higher amplitude (p = 0.08). The corresponding vena caval oxytocin
      pulses had a longer duration (p = 0.02) than those not linked to PGF(2alpha).
      Estradiol increased oxytocin receptor concentrations and the turnover of
      phosphatidylinositides (p = 0.02) without affecting PGF(2alpha) pulse
      characteristics. Onapristone increased (p = 0.03) PGF(2alpha) pulse amplitude.
      Although a lower than expected temporal correlation between oxytocin and
      PGF(2alpha) pulses was observed, the distinguishing characteristics of linked
      pulses may be indicative of their physiological significance.

PMID- 9160724
TI  - Effects of toremifene on neonatal rat uterine growth and differentiation.
AB  - In the developing rodent uterus, the estrogen agonist activity of
      triphenylethylene antiestrogens such as tamoxifen alters uterine luminal
      epithelium morphology and inhibits uterine gland genesis. We examined uterine
      growth and differentiation in female offspring from date-mated Sprague-Dawley
      rats given the structurally related antiestrogen, toremifene, by s.c. injection
      in 10 microl of sesame oil on postnatal days (PND) 1-5, 10-14, or 20-24.
      Toremifene given on PND 10-14, a period of rapid uterine gland differentiation,
      caused a dose-related increase in uterine weight, tripled luminal epithelium cell
      height, and completely inhibited uterine gland development on PND 14 at doses of
      10 microg or higher. Based on this dose-response analysis, a 10-microg dose of
      toremifene was chosen to assess uterine development after neonatal exposure (PND
      1-5). Uterine weights and luminal epithelium cell heights were significantly
      increased by toremifene on PND 5 but returned to control levels by PND 26.
      Uterine gland numbers were reduced to 50% those of controls on PND 26. Dose
      related uterine weight and luminal epithelium cell height increases were also
      observed in rats given toremifene on PND 20-24. This estrogen agonist activity of
      toremifene, revealed primarily in the uterine luminal epithelium, indicates that
      toremifene is developmentally toxic.

PMID- 9160725
TI  - Biochemical and molecular characterization of bovine fertilin alpha and beta
      (ADAM 1 and ADAM 2): a candidate sperm-egg binding/fusion complex.
AB  - Fertilin alpha and beta (previously known as PH-30 alpha and beta) are sperm
      surface proteins implicated in sperm-egg binding and membrane fusion. In this
      work we report the purification, characterization, and cloning of the bovine
      homologues of fertilin alpha and beta. Immunofluorescence and Western blotting,
      using polyclonal antibodies made against guinea pig fertilin, identified likely
      bovine fertilin alpha and beta homologues. These candidates were purified under
      nondenaturing conditions using lectin and ion-exchange chromatography and were
      subjected to amino acid sequence analysis. Degenerate oligonucleotides made from
      bovine N-terminal protein sequences and from guinea pig fertilin sequences were
      used to isolate clones encoding bovine fertilin alpha and beta from a bovine
      testis cDNA library. The predicted proteins have the same domain organization as
      guinea pig fertilin alpha and beta: pro, metalloprotease-like, disintegrin-like,
      and cysteine-rich domains, followed by an EGF-like repeat, a transmembrane
      domain, and a cytoplasmic tail. In contrast to the reported sequence of guinea
      pig fertilin alpha, the mature, proteolytically processed bovine fertilin alpha
      subunit contains a complete disintegrin-like domain, and a potential amphipathic
      beta strand, which may be involved in sperm-egg fusion. Gradient sedimentation
      experiments suggest that the fertilin alpha/beta heterodimer may be present on
      the sperm surface as a higher-order oligomer.

PMID- 9160726
TI  - Unusual ampullary sperm crypts, and behavior and role of the cumulus oophorus, in
      the oviduct of the least shrew, Cryptotis parva.
AB  - The gametes of the least shrew, Cryptotis parva, were studied in regard to their
      maturation and structure, and with particular emphasis on their behavior in the
      fallopian tube, from the time of ovulation until the appearance of two-cell
      embryos beginning some 9 h after ovulation. Cryptotis spermatozoa are organized
      according to the conventional eutherian mold, with the exception of a barbed
      perforatorium and an unusual plasma membrane density lent by a bristly coat where
      it overlies the acrosome rim. In the epididymis they undergo a maturation of the
      capacity for motility and an -S-S-related stabilization of the nucleus and tail
      organelles, with the cauda housing only approximately 4-5 million spermatozoa.
      Mating involves penile locking and also the deposition of a modest vaginal plug
      that covers the cervix. The short (4-5 mm) fallopian tube has three regions-a
      simple isthmus, a relatively narrow ampulla populated throughout by ciliated
      crypts, and a crypt-free terminal infundibulum-the fertilization site. Unlike the
      situation in most mammals, the tubal isthmus was devoid of spermatozoa in mated
      females before and after ovulation, which occurred approximately 13 h post-hCG
      and produced a mean of 5.7 ova. However, the ampulla then housed approximately
      1500 active cells in groups within the ciliated crypts, sometimes together with
      leukocytes but with few spermatozoa above in the infundibulum. Within about 1 h
      after their ovulation from approximately 400-microm follicles, eggs were
      penetrated while in the infundibulum despite the nonexpanded hyaluronidase
      resistant state of the cumulus oophorus. However, on moving down to the ampulla
      by 2-4 h after ovulation, the dense cumulus around fertilized eggs appeared to
      proliferate and began to disperse coincidentally with secretion of a
      hyaluronidase-sensitive matrix in which hundreds of motile spermatozoa often
      became enmeshed. This cumulus change also occurred around unfertilized eggs,
      though more slowly, but not around fertilized or unfertilized eggs cultured in
      vitro. Thus, cumulus matrix production appeared to be stimulated to an important
      degree by factors in the oviduct, not by preovulatory gonadotropins as in many
      mammals. Although cumulus-invested eggs were fertilized readily in vitro, cumulus
      free eggs of the same age were never fertilized, and spermatozoa bound to the
      zona pellucida had intact acrosomes. This and related evidence from other shrews
      makes it seem likely that the soricid cumulus has an essential role in
      fertilization and may induce the acrosome reaction.

PMID- 9160727
TI  - Multiple fucosyltransferases and their carbohydrate ligands are involved in
      spermatogenic cell-Sertoli cell adhesion in vitro in rats.
AB  - We have identified multiple fucosyltransferases (FTs) (alpha[1-2]-, alpha[1-3]-,
      alpha[1-4]-FTs) on cells of the rat seminiferous epithelium as demonstrated by
      fucose incorporation into phenyl-beta-D-galactoside (Ph-beta-D-Gal), 2'
      fucosyllactose (2'-FL), and lacto-N-fucopentaose-l (LNF I), respectively. Now,
      using fluorescence laser scanning cytometry, we report that multiple FTs are
      implicated in germ cell-Sertoli cell adhesion in vitro. Sertoli cells were
      isolated from 19- to 21-day-old CD rats and cultured for 6-10 days. Mixed germ
      cells were obtained by enzymatic dispersion of adult rat testis and cultured
      overnight before labeling with 10 microM acetoxymethyl ester derivative of the
      fluorescent indicator, calcein. The adherent cell analysis and sorting 570
      interactive laser cytometer was used to determine the number of labeled adherent
      germ cells on Sertoli cell monolayers in the presence or absence of a variety of
      low molecular weight acceptors for fucose. Coincubation of labeled germ cells
      with Sertoli cell monolayers in the presence of GDP-fucose, UDP-galactose, Ph
      beta-D-Gal, 2'-FL, LNF I, and Lewis-X and 3'-sialyl-Lewis-X oligosaccharides
      resulted in significant reduction of germ cell binding when compared to that of
      the untreated controls or of control samples incubated with cellobiose,
      melibiose, and alpha-D-mannopyranose, which do not serve as fucose acceptors. Our
      results suggest that multiple FTs and their lectin/selectin ligands are involved
      in mediating germ cell-Sertoli cell adhesion to form a cohesive epithelium and
      thus aid germ cell adluminal translocation within the seminiferous epithelium.

PMID- 9160728
TI  - Human decidual cell biosynthesis of leukemia inhibitory factor: regulation by
      decidual cytokines and steroid hormones.
AB  - The production of leukemia inhibitory factor (LIF) is suggested to be critical
      for the successful implantation of blastocysts into decidua, because LIF
      expression is essential for the implantation of mouse blastocytes. We
      investigated the regulation of LIF production by decidual cytokines and steroid
      hormones. Stimulation of decidual cells by interleukin-1, tumor necrosis factor
      alpha, or transforming growth factor beta augmented LIF production in a dose
      dependent manner. Moreover, estradiol, a steroid hormone that increases during
      ovulation and early pregnancy, also enhanced LIF production in a dose-dependent
      manner. These responses were blocked by protein kinase C (PKC) inhibitor but not
      by other kinase inhibitors, suggesting an important role of PKC in decidual LIF
      production mediated by cytokines and estradiol. We also showed that stimulating
      decidual cells with LIF failed to stimulate DNA synthesis and prolactin
      production in these cells. In summary, LIF was mainly localized in the decidual
      glands and stroma, and its production was increased by cytokines and estradiol in
      a dose-dependent fashion; but stimulation of decidual cells by LIF did not
      influence their proliferation or their prolactin production.

PMID- 9160729
TI  - Gonadotropins, serum, and amino acids alter nuclear maturation, cumulus
      expansion, and oocyte morphology in hamster cumulus-oocyte complexes in vitro.
AB  - Glucose, lactate, and pyruvate (the substrate triad), gonadotropins, serum, and
      amino acids were tested on maturation of cumulus-oocyte complexes (COCs) using a
      simple defined medium, Tyrode's-PVA (T-PVA). In experiment 1, effects of FSH (2
      microg/ml) and the substrate triad were tested using a 2 x 2 factorial design.
      After 12-13 h, nuclear maturation was depressed in the absence of the triad or
      with FSH (0-14% metaphase II [MII]) compared with the triad alone (92% MII, p <
      0.05). Subsequent experiments used as the base medium Tyrode's solution with the
      triad (TLP-PVA): adding 10% bovine calf serum (BCS) and gonadotropins (10
      microg/ml FSH, 10 microg/ml LH, or both) yielded nuclear maturation equivalent to
      that in medium alone (88-100% post-metaphase I [post-MI] oocytes). Responses with
      glutamine, or with 11 but not 20 amino acids, were equivalent to the response in
      BCS with gonadotropins (93-100% post-MI oocytes). Some cumulus expansion occurred
      in COCs matured with gonadotropins and BCS, or glutamine, or 11 amino acids, but
      was less extensive than for in vivo-matured COCs. Oocytes matured with
      gonadotropins and BCS, or glutamine, or 11 amino acids plus gonadotropins, but
      not medium alone, had normal-appearing first polar bodies. Another cytoplasmic
      marker, cortical distribution of microfilaments (detected by confocal
      microscopy), did not differ between in vitro- and in vivo-matured oocytes. We
      conclude that effects of gonadotropins on hamster nuclear maturation, cumulus
      expansion, and oocyte morphology are modulated by serum or amino acids;
      maturation conditions producing normal oocyte and cumulus morphologies are
      predicted to yield developmentally competent oocytes.

PMID- 9160730
TI  - Effect of the colony-stimulating factor-1 null mutation, osteopetrotic
      (csfm(op)), on the distribution of macrophages in the male mouse reproductive
      tract.
AB  - Macrophages are found throughout the male reproductive tract and its accessory
      glands. Mice homozygous for a null mutation (csfm(op)) in the gene for the
      mononuclear phagocytic growth factor colony-stimulating factor-1 (CSF-1) have a
      significantly lower density of macrophages, defined by the mononuclear phagocytic
      antigen F4/80, in the testis, cauda and caput epididymis, prostate, seminal
      vesicles, and vas deferens. These data indicate that CSF-1 is the major growth
      factor regulating the occurrence of macrophages in male reproductive tissues. The
      residual macrophages were correctly located in the tissue except in the caput
      epididymis, where they failed to take up positions adjacent to the tubular
      epithelium. Restoration of circulating CSF-1 concentrations in csfm(op)/csfm(op)
      males totally restored F4/80+ cell density in the testis and caput and cauda
      epididymis and partially restored their density in the vas deferens and seminal
      vesicles but failed to affect density in the prostate. This failure to correct
      all populations with circulating CSF-1 suggests the requirement for local
      synthesis of CSF-1 at appropriate developmental stages and/or its expression in a
      cell surface-associated form. The absence of macrophages in the testis and
      epididymis of csfm(op)/csfm(op) mice correlates with dysfunction in these
      tissues, suggesting that macrophages play important nonimmunological roles in
      these tissues.

PMID- 9160731
TI  - Pattern and source of secretion of relaxin in the reproductive cycle of the
      spotted hyena (Crocuta crocuta).
AB  - Female spotted hyenas are highly masculinized at birth and have no external
      vagina. Copulation with males and birth of young are accomplished through the
      central urogenital canal of the clitoris. This unusual adaptation requires
      remarkable changes in the elasticity of the connective tissues of the clitoris,
      without which neither copulation nor birth would be possible. We hypothesized
      that relaxin, a hormone that increases the extensibility of the connective
      tissues of the uterus and cervix of many other mammalian species, plays a role in
      the clitoral changes observed in hyenas. Serum relaxin was determined by specific
      RIA. Relaxin was not detected in serum of males, pubertal or nonpregnant adult
      females, or ovariectomized females. Immunoactive relaxin was detected in serum of
      juveniles at the time of initial growth of the urogenital meatus. High
      concentrations of immunoactive relaxin appeared in the serum of pregnant hyenas
      in the 2 wk preceding parturition. Immunoassays of extracts of hyena tissues and
      serum obtained from uterine and ovarian veins indicated that the placenta was the
      predominant source of relaxin, with possible ovarian contributions. Circulating
      relaxin decreased promptly following cesarean section near term. We conclude that
      relaxin secretion coincides with changes in extensibility of clitoral connective
      tissues 1) during growth of the clitoris in juveniles and 2) near the time of
      parturition in adults.

PMID- 9160732
TI  - Interaction of acrosome-reacted macaque sperm with the macaque zona pellucida.
AB  - In this study we investigated the ultrastructure of macaque sperm induced to
      acrosome-react with calcium ionophore A23187, and the interaction between these
      acrosome-reacted sperm and the macaque zona pellucida. Transmission electron
      microscopy revealed that the majority of ionophore-treated sperm retained the
      vesiculated acrosomal cap or "shroud." Untreated, acrosome-reacted sperm on the
      zona had a similar ultrastructural appearance. In sperm-zona binding experiments,
      a mean of 4.5 ionophore-treated sperm were bound per zona after 1 min of
      coincubation compared with 41 sperm per zona in the solvent control. Vigorous
      pipetting was used to remove the acrosomal shrouds from approximately 50% of
      acrosome-reacted sperm before incubation with oocytes. Significantly more of
      these mechanically treated sperm were bound to the zona after a 4-min
      coincubation compared with acrosome-reacted sperm that were not pipetted. The
      number of mechanically treated sperm bound to the zona was the same whether the
      sperm and oocytes were coincubated in calcium-free medium or in control medium.
      The percentage of mechanically treated sperm that were acrosome-reacted on the
      zona also was not different in the two media. We conclude that macaque sperm that
      undergo the acrosome reaction on the zona surface are bound by the acrosomal
      shroud before zona penetration. When sperm acrosome-react before interaction with
      the oocyte, their zona binding capacity is significantly reduced. Removal of the
      acrosomal shroud and exposure of the inner acrosomal membrane increases the
      affinity of sperm for the zona. This sequence occurs naturally during the
      transition from primary binding to secondary binding on the zona surface.

PMID- 9160733
TI  - Up-regulation of urokinase plasminogen activator messenger ribonucleic acid and
      protein in hen granulosa cells by transforming growth factor alpha in vitro
      during follicular development.
AB  - The aim of the present study was to examine the regulatory role of transforming
      growth factor alpha (TGF alpha) on urokinase plasminogen activator (uPA) gene
      expression and protein levels in hen granulosa cells from different stages of
      ovarian follicular development in vitro. Granulosa cells from the first (F1), the
      second and third (F2-3), and the fourth, fifth, and sixth (F4-6) largest
      preovulatory follicles were cultured for 21 h in the absence and presence of TGF
      alpha (10 ng/ml). The uPA mRNA abundance and protein content were determined by
      Northern and Western blot analysis, respectively. Cell-associated and secreted PA
      activity was measured by a fibrinolysis assay and characterized by zymography.
      Hen granulosa cells produce a uPA with a molecular mass of about 35 kDa and a
      transcript size of approximately 2.5 kb. Basal uPA mRNA abundance, protein
      content, and activity were highest in granulosa cells from F4-6 follicles and
      decreased with follicular maturation. Granulosa cell uPA mRNA levels, protein
      content, and activity were increased in the presence of TGF alpha, reaching
      maximal levels in granulosa cells from less mature follicles, although the
      percentage of stimulation was higher in cells from late stages of follicular
      development. These findings clearly demonstrate specific expression of uPA in
      proliferatively active granulosa cells and responsiveness of uPA to TGF alpha at
      both transcriptional and translational levels. They support the concept that PA
      of the urokinase type plays an important role in extracellular matrix remodeling
      during TGF alpha-induced granulosa cell proliferation and ovarian follicular
      growth.

PMID- 9160734
TI  - Changes in ribosomal ribonucleic acid content within in vitro-produced bovine
      embryos.
AB  - The abundance of 28S, 18S, and 5S rRNA was measured by Northern blot techniques
      applied to RNA samples extracted from bovine oocytes and preattachment embryos
      produced by in vitro procedures. Total RNA content was estimated by comparing the
      intensity of hybridization signals of 28S and 18S rRNA probes to embryo RNA
      samples and to standard curves generated from bovine ovary or bovine oviduct cell
      RNA. RNA content declined from the oocyte to the morula stage (2.4 +/- 0.3
      ng/oocyte, 1.7 +/- 0.5 ng/1-cell embryo, 2.2 +/- 0.9 ng/2- to 4-cell embryo, 0.8
      +/- 0.2 ng/6- to 8-cell embryo, and 0.7 +/- 0.2 ng/morula). A marked increase in
      RNA content, based on levels of hybridization to 28S and 18S rRNA, was observed
      in blastocysts, in which values averaged 5.3 +/- 0.6 ng/embryo. On a relative
      basis, 5S rRNA abundance followed a pattern similar to that of 28S and 18S rRNA
      across the early development period to the blastocyst stage.

PMID- 9160735
TI  - Immunohistochemical localization of testin in the female reproductive system of
      the rat is consistent with its involvement in the turnover of specialized
      junctional complexes.
AB  - The distribution of testin in the female reproductive system of rats throughout
      the estrous cycle was examined immunohistochemically. In ovarian follicles,
      immunostainable testin was localized at the junctions between adjacent granulosa
      cells. During follicular development, immunostainable testin surrounding the
      granulosa cells increased in every follicle but was reduced drastically when the
      follicle was undergoing atresia. Testin was also found in the junctions between
      adjacent germinal epithelial cells that covered the surface of the ovary, at the
      lower or the lower lateral borders of each cell. In the uterus and oviduct,
      immunostainable testin was detected only in the luminal and glandular epithelium,
      where it formed a polygonal network encircling the apical border of the
      epithelial cells. During the estrous cycle, there was no drastic change in the
      distribution of testin in the epithelial cells of the ovary. In the vaginal
      mucosa, testin was found to be localized only at the junction of the epithelial
      cells on the surface layer of the stratified epithelium; at different stages of
      the estrous cycle, distinctive staining for testin could be found at proestrus,
      metestrus, and diestrus, but not at estrus. It is postulated that testin is a
      cell junction-associated protein in the female reproductive system.

PMID- 9160736
TI  - Molecular cloning of sheep and goat ferredoxin reductase messenger ribonucleic
      acids, and identification of an alternatively spliced form of sheep ferredoxin
      reductase.
AB  - Complementary DNA clones of mRNAs for sheep and goat NADPH-ferredoxin reductases
      (ferredoxin NADP+ oxidoreductase, EC 1.18.1.2) were isolated by the reverse
      transcriptase polymerase chain reaction method, and the complete nucleotide
      sequences of the coding and 3'-flanking regions of these cDNA clones were
      determined. Comparative analysis using the deduced amino acid sequences of NADPH
      ferredoxin reductases clarified the interspecific conservation of the ferredoxin
      binding and flavin adenine dinucleotide (FAD)-binding regions, confirming the
      results reported previously. During this study, we happened to identify an
      alternatively spliced mRNA that completely lacks exon 3, just adjacent to the FAD
      binding region of the sheep NADPH-ferredoxin reductase cDNA clone. In the
      screening of other alternatively spliced mRNAs of NADPH-ferredoxin reductases
      derived from several steroidogenic organs, such as adrenocortices, testes, and
      ovaries of sheep and goats, only one kind of alternatively spliced mRNA as
      described above was detected in sheep adrenocortices. Then, we constructed
      Escherichia coli expression systems for these two forms of mRNA and analyzed
      their enzymatic properties. We found that the ability of the alternatively
      spliced NADPH-ferredoxin reductase protein to transfer electrons to ferredoxin is
      completely abolished because FAD binding is inhibited.

PMID- 9160737
TI  - Alpha2-adrenergic receptor-mediated Ca2+ influx and release in porcine myometrial
      cells.
AB  - We studied the mechanisms underlying alpha2-adrenergic receptor (AR)-mediated
      increase in intracellular free calcium ([Ca2+]i) in freshly dispersed myometrial
      cells from sows in the luteal phase of the estrous cycle. After the blockade of
      beta-ARs with propranolol, epinephrine increased [Ca2+]i dose-dependently in both
      the presence and absence of extracellular Ca2+. The rank order of alpha
      antagonists in inhibiting [Ca2+]i response to epinephrine was yohimbine > WB4101
      >> prazosin in both the presence and absence of extracellular Ca2+, suggesting
      that epinephrine acts on alpha(2A)-ARs to increase Ca2+ influx as well as Ca2+
      release from intracellular stores. Thapsigargin, the blocker of the Ca2+ pump in
      the sarcoplasmic reticulum, abolished the release but did not affect the influx.
      Pertussis toxin (PTX) inhibited the influx but failed to change the release.
      Nimodipine, an L-type Ca2+ channel blocker, nearly abolished the influx. The peak
      increase in [Ca2+]i caused by epinephrine was reached within 20 sec of
      administration. Intracellular cAMP concentrations were also decreased at 20 sec
      post-epinephrine. Epinephrine enhanced the L-type Ca2+ channel current, whereas
      forskolin suppressed it. Maximization of intracellular cAMP content by applying 8
      bromo-cAMP (100 microM) blocked the effect of epinephrine on the current. U
      73122, a phospholipase C inhibitor, reduced the Ca2+ release by epinephrine and
      oxytocin. Our results suggested that 1) activation of alpha2-ARs induces Ca2+
      influx through opening L-type Ca2+ channels as well as inducing Ca2+ release from
      intracellular stores, and 2) a PTX-sensitive G protein couples negatively to
      adenylyl cyclase, leading to a decrease in cAMP formation which may be involved
      in the activation of Ca2+ channels. In addition, our results are consistent with
      the coupling of alpha2-ARs to a PTX-insensitive G protein (G(q)) to release Ca2+
      from intracellular stores.

PMID- 9160738
TI  - Decidua-associated suppressor cells in abortion-prone DBA/2-mated CBA/J mice that
      release bioactive transforming growth factor beta2-related immunosuppressive
      molecules express a bone marrow-derived natural suppressor cell marker and gamma
      delta T-cell receptor.
AB  - The decidua of allopregnant mice contains a novel population of Thy1 Lyt1 CD4 CD8
      asialoGM1- non-B small lymphocytic suppressor cells that release transforming
      growth factor (TGF) SS2-related suppressor molecules. The "null" phenotype of
      this cell population is similar to some bone marrow-derived natural suppressor
      cell (NSC) populations, and the latter may release TGF(beta)s. We now report that
      the TGF beta2-producing suppressor cells in the uterine decidua of DBA/2-mated
      CBA/J female mice-linked to prevention of abortions-are inactivated effectively
      by 1E5/B5.1 but not by 2C1.1 rat monoclonal antibodies to murine pregnancy
      associated splenic NSC in the presence of complement. Immunostaining of a
      subpopulation of cells in decidua with 1E5/B5.1 but not with 2C1.1 was shown by
      flow cytometry. Release of suppressor factor was also abrogated by 1E5/B5.1 +
      complement but not by 2C1.1 + complement, and the suppressor factor was
      specifically neutralized by anti-TGF beta2 and not by anti-TGF beta3. Splenic
      pregnancy NSC are susceptible to 2C1.1, produce TGF beta1, and express CD3 and
      alpha beta T-cell receptor (TcR) chains. Release of suppressor factor by the
      decidual NSC was abrogated by treatment with anti-CD3 (145 2C11) and anti-TcR
      gamma delta (GL4) monoclonal antibodies + complement, but not by anti-TcR alpha
      beta (H57) + complement; and cells sorted using anti-TcR gamma delta (GL3)
      released suppressive activity in vitro. Slightly more suppressive activity was
      released by implantation-site decidua where there was no epithelium than from
      epithelialized inter-implantation-site decidua; no significant activity was
      released from placental tissue, but combining implantation-site tissue with
      placental tissue led to release of enhanced levels of immunosuppressive activity.
      There appear to be subtypes of bone marrow-derived TcR+ NSC with different
      phenotypes and tissue localization patterns in pregnancy. The previously reported
      dependence of decidual NSC activity on the presence of soluble signals from fetal
      trophoblast may be explainable by the ability of cells bearing TcR gamma delta to
      recognize and react to placental trophoblast cell antigen.

PMID- 9160739
TI  - Forward genetic approach strikes gold: cloning of a mammalian clock gene.

PMID- 9160740
TI  - Pre-mRNA processing and the CTD of RNA polymerase II: the tail that wags the dog?

PMID- 9160741
TI  - Mad cows meet psi-chotic yeast: the expansion of the prion hypothesis.

PMID- 9160742
TI  - Deadly conformations--protein misfolding in prion disease.

PMID- 9160743
TI  - Condensins, chromosome condensation protein complexes containing XCAP-C, XCAP-E
      and a Xenopus homolog of the Drosophila Barren protein.
AB  - We report here purification and characterization of chromosome condensation
      protein complexes (termed condensins) containing XCAP-C and XCAP-E, two Xenopus
      members of the SMC family. Sucrose density gradient centrifugation reveals two
      major forms of condensins. The 8S form is a heterodimer of XCAP-C and XCAP-E,
      whereas the 13S form contains three additional subunits. One of them is
      identified as a homolog of the Drosophila Barren protein whose mutation shows a
      defect in chromosome segregation. Chromosomal targeting of condensins is mitosis
      specific and is independent of topoisomerase IIalpha. 13S condensin is required
      for condensation, as demonstrated by immunodepletion and rescue experiments. Our
      results suggest that the condensin complexes represent the most abundant
      structural components of mitotic chromosomes and play a central role in driving
      chromosome condensation.

PMID- 9160744
TI  - Molecular mechanism of membrane protein integration into the endoplasmic
      reticulum.
AB  - As proteins are integrated into the membrane of the endoplasmic reticulum, some
      hydrophilic polypeptide segments are transported through the translocation
      channel, others remain in the cytosol, and hydrophobic transmembrane sequences
      are released into the lipid phase. We have addressed the molecular mechanism by
      which these events occur. We demonstrate that both the lumenal and the cytosolic
      domains of a membrane protein are synthesized while the ribosome is membrane
      bound, so that even cytosolic domains come in contact with the translocation
      channel. We also find that, before translation of the protein is terminated,
      transmembrane sequences can laterally exit the translocation channel and enter
      the lipid environment. These results have significant implications for the
      folding and assembly of membrane proteins.

PMID- 9160746
TI  - X-ray crystallography reveals a large conformational change during guanyl
      transfer by mRNA capping enzymes.
AB  - We have solved the crystal structure of an mRNA capping enzyme at 2.5 A
      resolution. The enzyme comprises two domains with a deep, but narrow, cleft
      between them. The two molecules in the crystallographic asymmetric unit adopt
      very different conformations; both contain a bound GTP, but one protein molecule
      is in an open conformation while the other is in a closed conformation. Only in
      the closed conformation is the enzyme able to bind manganese ions and undergo
      catalysis within the crystals to yield the covalent guanylated enzyme
      intermediate. These structures provide direct evidence for a mechanism that
      involves a significant conformational change in the enzyme during catalysis.

PMID- 9160745
TI  - The aqueous pore through the translocon has a diameter of 40-60 A during
      cotranslational protein translocation at the ER membrane.
AB  - Eukaryotic secretory proteins are cotranslationally translocated through the
      endoplasmic reticulum (ER) membrane via aqueous pores that span the lipid
      bilayer. Fluorescent probes were incorporated into nascent secretory proteins
      using modified Lys-tRNAs, and the resulting nascent chains were sealed off from
      the cytosol in fully assembled translocation intermediates. Fluorescence
      quenching agents of different sizes were then introduced into the ER lumen in
      order to determine which were small enough to enter the pore and to quench the
      fluorescence of probes inside the ribosome and/or the pore. These accessibility
      studies showed that the aqueous pore in a functioning translocon is 40-60 A in
      diameter, making it the largest hole observed to date in a membrane that must
      maintain a permeability barrier.

PMID- 9160747
TI  - Crystal structure of PI-SceI, a homing endonuclease with protein splicing
      activity.
AB  - PI-Scel is a bifunctional yeast protein that propagates its mobile gene by
      catalyzing protein splicing and site-specific DNA double-strand cleavage. Here,
      we report the 2.4 A crystal structure of the PI-Scel protein. The structure is
      composed of two separate domains (I and II) with novel folds and different
      functions. Domain I, which is elongated and formed largely from seven beta
      sheets, harbors the N and C termini residues and two His residues that are
      implicated in protein splicing. Domain II, which is compact and is primarily
      composed of two similar alpha/beta motifs related by local two-fold symmetry,
      contains the putative nuclease active site with a cluster of two acidic residues
      and one basic residue commonly found in restriction endonucleases. This report
      presents prototypic structures of domains with single endonuclease and protein
      splicing active sites.

PMID- 9160748
TI  - Small nucleolar RNAs direct site-specific synthesis of pseudouridine in ribosomal
      RNA.
AB  - Ten ACA yeast small nucleolar RNAs (snoRNAs) were shown to be required for site
      specific synthesis of pseudouridine psi in ribosomal RNA. A common secondary
      folding motif for the snoRNAs and rRNA target segments predicts that site
      selection involves: (1) base pairing of the snoRNA with complementary rRNA
      elements flanking the site of modification, and (2) identification of a uridine
      located at a near-constant distance from the snoRNA ACA box. The model is
      supported by mutations showing that: (1) reducing the complementarity between the
      snoRNA and rRNA disrupts psi formation, and (2) altering the distance between the
      ACA box and target uridine causes an adjacent uridine to be modified. This
      discovery implies that most snoRNAs function in targeting nucleotide modification
      in rRNA: ribose methylation for the box C/D snoRNAs and psi formation for the ACA
      snoRNAs.

PMID- 9160749
TI  - The CLAVATA1 gene encodes a putative receptor kinase that controls shoot and
      floral meristem size in Arabidopsis.
AB  - The shoot apical meristem is responsible for above-ground organ initiation in
      higher plants, accomplishing continuous organogenesis by maintaining a pool of
      undifferentiated cells and directing descendant cells toward organ formation.
      Normally, proliferation and differentiation are balanced, so that the structure
      and size of the shoot meristem is maintained. However, Arabidopsis plants
      homozygous for mutations at the CLAVATA1 (CLV1) locus accumulate excess
      undifferentiated cells. We describe the molecular cloning and expression pattern
      of the CLV1 gene. It encodes a putative receptor kinase, suggesting a role in
      signal transduction. The extracellular domain is composed of 21 tandem leucine
      rich repeats that resemble leucine-rich repeats found in animal hormone
      receptors. We provide evidence that CLV1 expression in the inflorescence is
      specifically associated with meristematic activity.

PMID- 9160750
TI  - The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene
      expression in CD4 T cells.
AB  - CD4 T cells potentiate the inflammatory or humoral immune response through the
      action of Th1 and Th2 cells, respectively. The molecular basis of the
      differentiation of these cells from naive T cell precursors is, however, unclear.
      We found that GATA-3 was selectively expressed in Th2 cells. GATA-3 is expressed
      at a high level in naive, freshly activated T cells and Th2 lineage cells, but
      subsides to a minimal level in Th1 lineage cells as naive cells commit to their
      Th subset. Antisense GATA-3 inhibited the expression of all Th2 cytokine genes in
      the Th2 clone D10. GATA-3 directly activated an IL-4 promoter-luciferase reporter
      gene in M12 cells. In transgenic mice, elevated GATA-3 in CD4 T cells caused Th2
      cytokine gene expression in developing Th1 cells. Thus, GATA-3 is necessary and
      sufficient for Th2 cytokine gene expression.

PMID- 9160751
TI  - mRNA silencing in erythroid differentiation: hnRNP K and hnRNP E1 regulate 15
      lipoxygenase translation from the 3' end.
AB  - Although LOX mRNA accumulates early during differentiation, a differentiation
      control element in its 3' untranslated region confers translational silencing
      until late stage erythropoiesis. We have purified two proteins from rabbit
      reticulocytes that specifically mediate LOX silencing and identified them as
      hnRNPs K and E1. Transfection of hnRNP K and hnRNP E1 into HeLa cells
      specifically silenced the translation of reporter mRNAs bearing a differentiation
      control element in their 3' untranslated region. Silenced LOX mRNA in rabbit
      reticulocytes specifically coimmunoprecipitated with hnRNP K. In a reconstituted
      cell-free translation system, addition of recombinant hnRNP K and hnRNP E1
      recapitulates this regulation via a specific inhibition of 80S ribosome assembly
      on LOX mRNA. Both proteins can control cap-dependent and internal ribosome entry
      site-mediated translation by binding to differentiation control elements. Our
      data suggest a specific cytoplasmic function for hnRNPs as translational
      regulatory proteins.

PMID- 9160752
TI  - In vitro reconstitution of the late steps of genetic recombination in E. coli.
AB  - Purified proteins have been used to reconstitute an in vitro system for the
      medial-to-late stages of recombination in E. coli. In this system, RecA protein
      formed recombination intermediates that were processed by the actions of the
      RuvA, RuvB, and RuvC proteins. RuvAB was found to promote branch migration, to
      dissociate the RecA filament, and to modulate the orientation of cleavage of
      Holliday junction resolution by RuvC. Monoclonal antibodies directed against
      RuvA, RuvB, or RuvC inhibited resolution in the reconstituted system. Specific
      protein-protein interactions between the branch migration motor (RuvB) and the
      resolvase (RuvC) were also observed. These results provide evidence for
      coordinated action during the late stages of recombination, possibly involving
      the assembly of a RuvABC branch migration/resolution complex.

PMID- 9160753
TI  - Transcription factor Sp1 is essential for early embryonic development but
      dispensable for cell growth and differentiation.
AB  - Transcription factor Sp1 has been implicated in the expression of many genes.
      Moreover, it has been suggested that Sp1 is linked to the maintenance of
      methylation-free CpG islands, the cell cycle, and the formation of active
      chromatin structures. We have inactivated the mouse Sp1 gene. Sp1-/- embryos are
      retarded in development, show a broad range of abnormalities, and die around day
      11 of gestation. In Sp1-/- embryos, the expression of many putative target genes,
      including cell cycle-regulated genes, is not affected, CpG islands remain
      methylation free, and active chromatin is formed at the globin loci. However, the
      expression of the methyl-CpG-binding protein MeCP2 is greatly reduced in Sp1-/-
      embryos. MeCP2 is thought to be required for the maintenance of differentiated
      cells. We suggest that Sp1 is an important regulator of this process.

PMID- 9160754
TI  - Skeletal and CNS defects in Presenilin-1-deficient mice.
AB  - Presenilin-1 (PS1) is the major gene responsible for early-onset familial
      Alzheimer's disease (FAD). To understand the normal function of PS1, we have
      generated a targeted null mutation in the murine homolog of PS1. We report that
      PS1-/- mice die shortly after natural birth or Caesarean section. The skeleton of
      homozygous mutants is grossly deformed. Hemorrhages occur in the CNS of PS1 null
      mutants with varying location, severity, and time of onset. The ventricular zone
      of PS1-/- brains is markedly thinner by embryonic day 14.5, indicating an
      impairment in neurogenesis. Bilateral cerebral cavitation caused by massive
      neuronal loss in specific subregions of the mutant brain is prominent after
      embryonic day 16.5. These results show that PS1 is required for proper formation
      of the axial skeleton, normal neurogenesis, and neuronal survival.

PMID- 9160757
TI  - Smoking related to 24-h ambulatory blood pressure and heart rate: a study in 352
      normotensive Danish subjects.
AB  - This study shows the association between smoking and both office and ambulatory
      blood pressure. By means of stratification, a uniform number of subjects of both
      sexes and spanning 6 decades (aged 20 to 79 years) were recruited randomly from
      the local community register. A total of 352 subjects participated, including 161
      smokers. Smokers (both sexes and all age groups summed), as compared with
      nonsmokers had statistically significant lower office blood pressure as follows
      (mean systolic +/- SED/mean diastolic +/- SED): (systolic and diastolic, -6.8 +/-
      2.1/-3.9 +/- 1.3); day ambulatory blood pressure (diastolic, /-2.8 +/- 1.0); and
      night ambulatory blood pressure (systolic and diastolic, -4.2 +/- 1.8/-3.9 +/-
      1.1). The intraperson variability of the day ambulatory blood pressure (as
      measured every 15 min) was identical for the smokers and the nonsmokers. Smokers
      were found to have a diminished "white coat" effect; this diminished white coat
      effect has not previously been described. The major white coat effect was seen in
      the older nonsmokers, whereas the diminished white coat effect was most
      pronounced in the older male smokers and in the younger female smokers. Smokers
      seem to have a diminished white coat effect, as well as a lower ambulatory blood
      pressure throughout the day (diastolic) and at night (systolic and diastolic).
      The similar intraperson variability found in the smokers' and nonsmokers' blood
      pressure further speaks for a consistently lower blood pressure in smokers as
      compared with nonsmokers.

PMID- 9160755
TI  - Positional cloning of the mouse circadian clock gene.
AB  - We used positional cloning to identify the circadian Clock gene in mice. Clock is
      a large transcription unit with 24 exons spanning approximately 100,000 bp of DNA
      from which transcript classes of 7.5 and approximately 10 kb arise. Clock encodes
      a novel member of the bHLH-PAS family of transcription factors. In the Clock
      mutant allele, an A-->T nucleotide transversion in a splice donor site causes
      exon skipping and deletion of 51 amino acids in the CLOCK protein. Clock is a
      unique gene with known circadian function and with features predicting DNA
      binding, protein dimerization, and activation domains. CLOCK represents the
      second example of a PAS domain-containing clock protein (besides Drosophila
      PERIOD), which suggests that this motif may define an evolutionarily conserved
      feature of the circadian clock mechanism.

PMID- 9160756
TI  - Functional identification of the mouse circadian Clock gene by transgenic BAC
      rescue.
AB  - As a complementary approach to positional cloning, we used in vivo
      complementation with bacterial artificial chromosome (BAC) clones expressed in
      transgenic mice to identify the circadian Clock gene. A 140 kb BAC transgene
      completely rescued both the long period and the loss-of-rhythm phenotypes in
      Clock mutant mice. Analysis with overlapping BAC transgenes demonstrates that a
      large transcription unit spanning approximately 100,000 base pairs is the Clock
      gene and encodes a novel basic-helix-loop-helix-PAS domain protein.
      Overexpression of the Clock transgene can shorten period length beyond the wild
      type range, which provides additional evidence that Clock is an integral
      component of the circadian pacemaking system. Taken together, these results
      provide a proof of principle that "cloning by rescue" is an efficient and
      definitive method in mice.

PMID- 9160758
TI  - Effects of verapamil SR, trandolapril, and their fixed combination on 24-h blood
      pressure: the Veratran Study.
AB  - The Veratran study investigated the antihypertensive efficacy of verapamil
      sustained release (SR) (180 mg), trandolapril (1 mg), and their fixed combination
      during a 24-h period. After a 4-week placebo run-in period, 272 patients (age 49
      +/- 9 years, mean +/- SD) with essential hypertension and a clinic diastolic
      blood pressure > or =100 mm Hg were randomized to verapamil, trandolapril, their
      fixed combination, or placebo for 8 weeks, according to a multicenter double
      blind parallel group study design. Clinic and semiautomatic blood pressure at
      trough and 24-h ambulatory blood pressure were measured at the end of run-in
      period and after 8 weeks of treatment. In the 234 patients included in the
      efficacy analysis, run-in clinic and semiautomatic blood pressures were reduced
      by verapamil, trandolapril, and combined verapamil and trandolapril significantly
      more than by placebo. The reductions obtained with the combination were
      significantly greater than those obtained by verapamil alone. Twenty-four-hour
      average blood pressures were not modified by placebo and were reduced by 8/6 mm
      Hg (systolic/diastolic) by verapamil, 11/7 mm Hg by trandolapril, and 14/11 mm Hg
      by the combination of the two drugs. The differences between the effect of the
      combination and the combination components were, in most instances, statistically
      significant. The verapamil-trandolapril combination was more effective also on
      day average blood pressure and superior to the monotherapies for the trough-to
      peak ratio of the antihypertensive effect as well. Twenty-four-hour heart rate
      was slightly but significantly reduced by verapamil and the reduction was
      manifest in the group taking verapamil plus trandolapril. Thus, the
      antihypertensive treatment with the fixed verapamil SR-trandolapril combination
      is more effective and balanced over the 24 hours than the effect of the
      combination components administered alone.

PMID- 9160759
TI  - Frequency shift in baroregulatory oscillation in borderline hypertensive
      subjects.
AB  - The aim of this study was to quantify the frequency shift in vasomotor
      oscillations in blood pressure we observed in borderline hypertensive individuals
      in our previous study. Electrocardiogram and intraarterial blood pressure were
      recorded in 33 normotensive, 29 borderline hypertensive, and 33 mildly
      hypertensive men (aged 35 to 45 years). Five-minute stationary periods in supine,
      sitting, and standing positions, and during sleep were extracted from the
      recordings for autoregressive frequency domain analysis. In borderline
      hypertensive subjects vasomotor oscillations in the range of 0.05 to 0.12 Hz in
      blood pressure and heart rate, assumed to be associated with baroreceptor
      activity, were shifted to lower values as compared with the other two groups. The
      frequency shift was assessed by median frequency of the oscillations. Significant
      between-group differences were observed in the supine and sitting positions. No
      significant between-group differences were seen in normalized spectral power
      estimates. Further studies are required to determine whether the frequency shift
      provides prognostic information on cardiovascular morbidity.

PMID- 9160760
TI  - Left ventricular mass is better correlated with arising blood pressure than with
      office or occasional blood pressure.
AB  - The peak incidence of cardiovascular complications in the morning points to a
      possible role of the abrupt increase in blood pressure on arising. However, there
      is as yet no firm evidence linking the extent of the elevation in blood pressure
      on arising and the risk of cardiovascular complications. We sought a correlation
      between blood pressure on arising and left ventricular mass in a population of
      181 previously untreated hypertensive patients. Ambulatory blood pressure was
      measured over a 24-h period, and each patient was requested to trigger a blood
      pressure determination immediately after standing on arising in the morning. Left
      ventricular mass was measured with M-mode echocardiography and indexed for
      height, height(2.7), and body surface area. The systolic blood pressure on
      arising was significantly (P <.01) better correlated than office blood pressure
      with left ventricular mass index and wall thickness. On multivariate analysis,
      the values of systolic blood pressure on arising and mean 24-h systolic blood
      pressure contributed significantly and independently to the correlation with left
      ventricular mass and wall thickness. These observations point to the significance
      of the arising blood pressure. A marked abrupt daily elevation in blood pressure
      on arising, then maintained for a certain time, could contribute to the
      development of left ventricular hypertrophy and may constitute a trigger for
      cardiovascular complications.

PMID- 9160761
TI  - Arterial disease in dipper and nondipper hypertensive patients.
AB  - Carotid artery and small vessel structural changes were evaluated in 45 dipper
      and 45 nondipper hypertensive subjects matched for sex, age, body mass index,
      smoking habit, and serum lipids. Patients underwent carotid ultrasonography to
      evaluate lumen diameter, intima-media thickness, cross-sectional area, and
      atherosclerotic plaques, and plethysmographic examination to record minimum
      forearm vascular resistance. In the whole study population, carotid cross
      sectional area and prevalence of atherosclerotic plaques tended to be higher in
      nondippers than in dippers (19.9 +/- 6.0 v 17.5 +/- 6.1 mm2, P = .07, and 40% v
      26%, P = .18), whereas intima-media thickness and minimum forearm vascular
      resistance were significantly higher in nondippers than in dippers (0.89 +/- 0.12
      v 0.8 +/- 0.15 mm, P < .02, and 2.53 +/- 0.3 v 2.34 +/- 0.3 arbitrary resistance
      units (RU), P < .02). When gender was taken into account, different results were
      obtained in men and women. In men, vascular characteristics were not
      significantly different between dippers and nondippers. In women, carotid cross
      sectional area and prevalence of atherosclerotic plaques tended to be higher in
      nondippers than in dippers (18.3 +/- 4.9 v 15.5 +/- 4.5 mm2, P = .06, and 40% v
      15%, P = .15), and intima-media thickness and minimum forearm vascular resistance
      were significantly higher in nondippers than in dippers both before (0.84 +/- 0.1
      v 0.73 +/- 0.1 mm, P < .01, and 2.38 +/- 0.3 v 2.16 +/- 0.2 RU, P < .01) and
      after adjustment for 24-h blood pressure. In conclusion, our data suggest that
      the progression of vascular disease may be differently affected in the two sexes
      by a different circadian blood pressure profile.

PMID- 9160763
TI  - Renal sodium pump regulation in deoxycorticosterone salt hypertension in the rat.
AB  - The renal sodium pump participates in sodium homeostasis and has been predicted
      to have a role in salt dependent forms of hypertension. However, the status of
      the renal sodium pump in volume-dependent hypertension is unclear. We assessed
      the renal sodium pump and its activity in the deoxycorticosterone acetate (DOCA)
      salt model in rats, a model of volume-dependent hypertension. Sprague-Dawley rats
      on ad libitum diet were compared with four groups of litter mates receiving high
      or low salt diets, with or without DOCA administration. The renal sodium pump
      evaluation included measurement of hydrolytic activity, ouabain binding capacity
      and affinity, sodium activation, active pump units (determined by phosphoenzyme
      level), dephosphorylation rate, and isoform specific molecular expression.
      Intrinsic enzyme properties, including sodium and ouabain affinities, as well as
      turnover rate per sodium pump, were identical among the five groups. In contrast,
      the combination of DOCA and high salt intake (DOCA high salt) produced marked,
      significant increases in hydrolytic activity, ouabain binding capacity,
      phosphoenzyme level, and alpha1-isoform expression. DOCA low salt animals showed
      much smaller but significant increases in pump number. We conclude that DOCA and
      volume expansion may each alter renal sodium pump regulation, but volume
      expansion is clearly dominant. Increased renal sodium pump activity in DOCA high
      salt animals would, if unmitigated, favor sodium reabsorption and may contribute
      to hypertension.

PMID- 9160762
TI  - The angiotensin converting enzyme and blood pressure in Jamaicans.
AB  - An insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme
      gene influences the level of serum angiotensin converting enzyme activity and has
      been associated with risk of several cardiovascular conditions. The relationship
      to blood pressure remains uncertain, however. We conducted a population-based
      survey in Kingston, Jamaica, to examine the association between angiotensin
      converting enzyme genotype, angiotensin converting enzyme serum activity and
      blood pressure. Serum angiotensin converting enzyme activity was measured and
      genotyping performed for the I/D polymorphism in 500 community residents. The
      overall prevalence of the D allele was 59.3%. Angiotensin converting enzyme
      genotype was not significantly related to blood pressure (P = .16), although it
      did influence angiotensin-converting enzyme activity, leading to an increase of
      35% among individuals with the DD as compared with II genotype. Angiotensin
      converting enzyme levels were significantly higher in hypertensives as compared
      with normotensives (P < .05). A modest correlation was observed between blood
      pressure and angiotensin converting enzyme activity among untreated individuals
      (r = 0.11; P = .04), although this did not persist in multivariate analysis. A
      relationship between body mass index and angiotensin converting enzyme activity
      was identified in both men and women that was independent of genotype. These data
      demonstrate findings among blacks which are consistent with other studies and
      suggest a relationship between angiotensin converting enzyme genotype, and serum
      activity which is influenced by both genetic and environmental factors. The
      potential role of ACE on blood pressure control in the population remains
      uncertain.

PMID- 9160764
TI  - Characterization of arterial antigens using arterial antigen-reactive T cell
      clones from spontaneously hypertensive rats.
AB  - We have previously demonstrated that arterial antigens derived from the aorta of
      spontaneously hypertensive rats (SHRs) stimulate arterial antigen-reactive T cell
      clones established from the spleens of SHR to proliferate and release cytokines.
      To identify immunogenic protein components associated with the arterial wall,
      arterial antigen-reactive T cell clones were tested against arterial antigens
      separated by SDS-PAGE and transferred to nitrocellulose. The greatest T cell
      reactivity was obtained with protein bands of molecular weight 66 kDa, 50 kDa,
      and 45 kDa. T cell clones reactive against the 50 and 45 kDa antigens from gels
      failed to respond to proteins of other molecular weight (M(r)) separated under
      reducing or nonreducing conditions, suggesting that these molecules are not
      subunits of larger proteins and may represent monomeric antigens polymerized into
      the arterial wall. These data suggest that certain epitopes of arterial wall
      antigens are immunogenic. T cells activated with these immunogenic epitopes could
      initiate or perpetuate vasculitis in the arteries of hypertensive rats.

PMID- 9160765
TI  - The effects of isradipine and spirapril as monotherapy and combined therapy on
      blood pressure, renal hemodynamics, natriuresis, and urinary kallikrein in
      hypertensive nephropathy.
AB  - In this cross-over, double-blind study, 12 essential hypertensive patients (stage
      I, II, and III) with glomerular filtration rate (GFR) between 50 to 80
      mL/min/1.73 m2, were submitted to 4 weeks of placebo followed by 12 weeks with
      isradipine SRO (IS) 5 mg, spirapril (SP) 6 mg, and isradipine plus spirapril (IS
      + SP). The study evaluated the effects of these drugs on GFR ((99m)Tc DTPA),
      effective renal plasma flow (ERPF) ((131)I-orthoiodohippurate), urinary sodium
      excretion (UNaV), urinary kallikrein excretion (UKal), urinary albumin excretion
      (UAE), and plasma renin activity (PRA). The three protocols significantly reduced
      mean blood pressure (128 v 107 mm Hg; 126 v 112 mm Hg; 129 v 104 mm Hg with IS,
      SP and IS + SP, respectively). ERPF and GFR did not change. UNaV increased
      significantly after IS (0.17 v 0.22 mEq/min) and IS + SP (0.18 v 0.24 mEq/min).
      UKal increased significantly after IS (58.6%) and IS + SP (53.6%). UAE decreased
      significantly only after SP. PRA increased significantly after IS (1.31 v 2.84
      ng/mL/h), SP (1.10 v 2.15 ng/mL/h), and after IS + SP (1.23 v 3.21 ng/mL/min). In
      conclusion, IS, SP and IS + SP were effective in reducing blood pressure while
      keeping renal function stable. Only SP significantly decreased UAE. Enhanced UKal
      may have played a role in natriuresis observed after IS and IS + SP.

PMID- 9160766
TI  - Does orthostatic testing have any role in the evaluation of the young subject
      with mild hypertension?: an insight from the HARVEST study.
AB  - The aim of the study was to assess the clinical significance of the blood
      pressure (BP) reaction to standing in 1029 stage I hypertensives. Office BP was
      measured six times in the supine position and six times after 2 min of standing.
      All subjects underwent 24-h ambulatory BP monitoring, and measurements of 24-h
      urinary epinephrine and norepinephrine excretion. Echocardiography was performed
      in 636 patients. With use of mixture analysis we could single out a population
      with abnormal diastolic BP response to standing (hyperreactors, n = 95). These
      subjects had a diastolic BP increase from lying to standing of >11 mm Hg. The
      other subjects were defined as normoreactors (n = 934). Office systolic BP was
      similar in the two groups. Diastolic BP was lower (91 +/- 6 mm Hg v 95 +/- 5 mm
      Hg, P < .0001) and heart rate was higher in the hyperreactors (77 +/- 10
      beats/min v 75 +/- 9 beats/min, P = .004). After adjusting for age, gender, and
      smoking habits the statistical significance did not change. Adjusted 24-h
      systolic BP (P = .02) and diastolic BP (P = .02) were higher in the hyperreactors
      than in the normoreactors. Hyperreactors were characterized by higher cardiac
      index (3.2 +/- 0.8 L/min/m2 v 3.0 +/- 0.7 L/min/m2, P = .008 for adjusted
      values), lower total peripheral resistance (1420 +/- 330 dyne/sec/cm(-5) v 1600
      +/- 380 dyne/sec/cm(-5), P = .003), and higher urinary norepinephrine output
      (114.9 +/- 80.3 microg/24 h v 90.6 +/- 78.5 microg/24 h, P = .03). Dimensional
      echocardiographic data and albumin excretion rate did not differ between the two
      groups. In conclusion, mixture analysis allowed us to identify a population of
      young mild hypertensives with exaggerated BP response to standing. Hyperreactors
      were characterized by higher whole-day BP and by a hyperkinetic hemodynamic
      pattern as a result of increased sympathetic tone.

PMID- 9160767
TI  - Prognostic value of ambulatory measurement of the timing of Korotkoff sounds in
      elderly hypertensives: a pilot study.
AB  - Alteration in the physical properties of the large arteries is probably an
      important contributory factor in morbidity and mortality in the elderly as well
      as in patients with hypertension or diabetes. We have developed a simple method
      based on the ambulatory measurement of the timing of Korotkoff sounds (QKD
      interval), together with blood pressure, to assess these properties. We report
      its prognostic value in a retrospective survey of elderly hypertensives. We
      included in this study 134 hypertensive patients over 45 years of age with no
      cardiovascular complications, either receiving placebo or prior to treatment with
      antihypertensive medication and seen between January 1992 and July 1993. In June
      1995, a survey was carried out to determine outcome by contacting the patients
      themselves and their family physicians. Data on outcome were obtained for 111
      patients with a mean follow-up period of 30 +/- 8 months. At least one
      cardiovascular complication was recorded during the follow-up period in 14
      patients. From the Cox model, data obtained from QKD monitoring, namely the
      QKD(100-60), was the best predictor of complications and remained significant (P
      < .01) even after introduction of age, mean 24 h SBP, gender, and smoking into
      the model. A QKD(100-60) below 187 msec was accompanied by a relative hazard of
      cardiovascular complications adjusted for age and mean 24 h BP of 7.3 (95%
      confidence interval: 2.9 to 11.7). The indices provided by the ambulatory
      measurement of QKD interval are significant predictors of cardiovascular
      complications independently of age and BP. This new method seems to add useful
      information to classic ambulatory blood pressure monitoring. However this will
      require confirmation in a large prospective study.

PMID- 9160768
TI  - Angiotensin I converting enzyme gene polymorphism in Chinese patients with
      hypertension.
AB  - Reports from different ethnic populations failed to show consistent findings on
      the association of hypertension with insertion/deletion (I/D) polymorphism of the
      angiotensin I converting enzyme (ACE) gene. In this population association study
      in Chinese, we compared the distribution of the ACE genotypes and allele
      frequency in 150 healthy controls with normal blood pressure and 148 hypertensive
      patients categorized by age. Although the frequencies of homozygote deletion (DD)
      genotype and deletion allele were greater in Chinese with hypertension than in
      normotensive controls (0.23 vs 0.13 and 0.44 v 0.37, respectively), the
      differences were not significant by chi2 analysis (P = .07 and .09,
      respectively). Furthermore, we did not find the trend of decreasing number of DD
      genotype in older hypertensive Chinese patients. The results indicated a much
      lower prevalence of ACE/DD genotype in Chinese than in Caucasians and a modest
      association between I/D polymorphism of the ACE gene and hypertension in Chinese.

PMID- 9160769
TI  - Diurnal blood pressure rhythm in hypertensives with parental history of stroke.
AB  - To investigate whether the lack of nocturnal decline of blood pressure
      (nondipper) is a primary cause of stroke or a secondary abnormality due to stoke,
      we examined the relation between the blood pressure variation and parental
      history of stroke in 110 hypertensive patients. In nondippers (n = 54), the
      frequency of positive parental history of stroke was significantly higher than in
      dippers (n = 56) (53.7% v 33.9%, chi2 = 4.37, P = .0366). We observed a
      significant increase in the incidence of positive parental history of stroke in
      nondippers, suggesting that some genetic factors may regulate blood pressure
      profiles before stroke develops.

PMID- 9160770
TI  - Calcium channel blockers for hypertension: dissecting the evidence for adverse
      effects.
AB  - Safety in the drug treatment of hypertension can only be seen in relation to
      efficacy, which has now come to mean not just blood pressure (BP) reduction but
      improvements in hard end points including mortality. Information on safety can
      come from a variety of sources, in an ascending hierarchy, which is as follows:
      case-control studies, cohort studies, randomized control trials (RCTs), and
      metaanalyses based on good RCTs. Only in the case of metaanalyses are definite
      criteria for acceptability established, but evaluation of case-control and cohort
      studies remains subjective. Despite these reserves about the data sources, it is
      proposed that the case-control study pointing to the risk of acute myocardial
      infarction during therapy with short-acting calcium channel blockers (CCBs) can
      be balanced out by another better more recent study, and by a large cohort study
      from Israel. In a very elderly population, a well-designed cohort study strongly
      suggests that short-acting nifedipine can be linked to increased mortality and
      that the specific links may be with a high dose and when the initial BP is less
      than 160/90 mm Hg. However, initial BP was only available in an unspecified
      number of patients. The risk of using short-acting verapamil was no more than
      that of beta-blockade. These differences can be attributed at least in part to
      the low catecholamine profile of verapamil and the marked rapid adrenergic
      activation with short-acting nifedipine, which could also explain the adverse
      effects found when this agent is given to patients with acute coronary syndromes.
      During the chronic use of long-acting dihydropyridine (DHP) CCBs, most evidence
      suggests that there is little or no catecholamine activation, or in the case of
      amlodipine, even a decrease in plasma catecholamine levels. These differences may
      explain why the expected regression of left ventricular hypertrophy is obtained
      with long- but not short-acting DHPs. At present the results of several large
      randomized controlled trials with long-acting CCBs are awaited. In the meantime,
      when the decision has been made to use a CCB, the preferential choice is for the
      use of a non-DHP for hypertension with clinical ischemia or for postinfarct
      hypertension, for a long-acting CCB for the control of left ventricular
      hypertrophy, and for the DHP amlodipine when there is associated depression of
      myocardial function.

PMID- 9160771
TI  - When hypertension is resistant...we think it over!

PMID- 9160772
TI  - Hormone replacement therapy with conjugated estrogens and high blood pressure:
      response to Dr. Jespersen.

PMID- 9160773
TI  - Trough-to-peak ratio of angiotensin converting enzyme inhibitors and calcium
      antagonists.

PMID- 9160774
TI  - Blood pressure reactivity and vascular disease: call off the funeral.

PMID- 9160775
TI  - The great salt war.

PMID- 9160776
TI  - Introduction to the Dahl symposium.

PMID- 9160777
TI  - Salt and blood pressure: population and individual perspectives.
AB  - The need to reduce the amount of salt in the diet has remained a very
      controversial issue in spite of strong evidence from animal experimental and
      human studies that increased salt intake is associated with increased blood
      pressure levels. The fundamental problem is the confusion between clinical,
      preventive medicine, and public health approaches. Reducing salt intake is not as
      effective as drug therapy to treat hypertension (clinical model). Individual
      preventive medicine approaches aimed at high risk populations are effective, but
      the efficacy is limited by the size of the population at risk and the intensity
      of the intervention. The public health approach to gradual reduction of available
      salt in the diet is likely to result in decreased morbidity and mortality with
      little inconvenience to the public.

PMID- 9160778
TI  - Salt--more adverse effects.
AB  - Salt intake has been shown to be the most important determinant of blood pressure
      differences both between populations and within populations, as well as the main
      determinant of the rise in blood pressure with increasing age. In spite of this
      overwhelming evidence, the food industry for commercial reasons has sustained an
      artificial debate about the importance of salt intake. This has distracted
      attention from the other serious effects that a high salt intake may have. A high
      salt intake (a) exacerbates conditions where there is already sodium and water
      retention; (b) is the rate limiting factor for carcinoma of the stomach; (c)
      contributes to left ventricular hypertrophy; (d) is likely to hasten
      deterioration of renal function and renal disease; (e) is an exacerbating factor
      in asthma; and (f) increasingly is suggested as a major aggravating factor in
      osteoporosis.

PMID- 9160779
TI  - Epidemiologic evidence on salt and blood pressure.

PMID- 9160780
TI  - Sodium, potassium, and blood pressure.

PMID- 9160781
TI  - Mechanisms of abnormal renal sodium handling in obesity hypertension.
AB  - Obesity-induced hypertension, like all forms of experimental and human
      hypertension studied thus far, is associated with renal dysfunction characterized
      by the resetting of pressure natriuresis. In obese subjects, this resetting is
      primarily a result of increased renal tubular reabsorption as glomerular
      filtration rate and renal blood flow are markedly elevated. Obesity activates the
      sympathetic nervous and renin-angiotensin systems, and causes insulin resistance
      and hyperinsulinemia, all of which have been postulated to increase tubular
      reabsorption and raise blood pressure. In humans and dogs, chronic
      hyperinsulinemia, comparable to that found in obesity, does not cause
      hypertension even in the presence of insulin resistance. Activation of the
      sympathetic nervous system appears to be important in obesity, as chronic
      adrenergic blockade or renal denervation greatly ameliorates the hypertension
      associated with weight gain. Resetting of pressure natriuresis in obesity may
      also be attributable to altered intrarenal forces caused by histologic changes in
      the renal medulla that may compress the loops of Henle and vasa recta, increase
      tubular sodium reabsorption, and activate the renin-angiotensin system. The
      quantitative importance of these intrarenal changes and their interrelationship
      with neurohumoral activation in obesity is an important area for further
      investigation.

PMID- 9160782
TI  - Time course of inhibition of hypertension by antisense oligonucleotides targeted
      to AT1 angiotensin receptor mRNA in spontaneously hypertensive rats.
AB  - Antisense oligodeoxynucleotides (AS-ODN) can be designed to provide inhibition of
      a specific protein. Since angiotensin receptors are involved in blood pressure
      regulation we constructed AS-ODN to angiotensin II type-1 receptor (AT1) mRNA.
      When given centrally, the AS-ODN reduces blood pressure in spontaneously
      hypertensive rats (SHR) 24 h after injection. To study the time course of a
      single AS-ODN injection on blood pressure and heart rate, groups of SHR were
      injected intracerebroventricularly (icv) with either single dose of AS-ODN or
      scrambled (SC) ODN and blood pressure was recorded through implanted catheters
      daily for up to 9 days. Blood pressure decreased significantly in the AS-ODN
      treated rats compared to the SC-ODN rats for up to 7 days. The maximum decrease
      (38 mm Hg) occurred at 3 days. There appeared to be no toxic reaction or side
      effects and the blood pressure level had recovered by days 8 and 9. Heart rate
      was not altered by AS-ODN treatment. To test that the ODN was entering the brain
      tissue, fluorescein-isothiocyanate labelled (FITC) ODN was injected in Sprague
      Dawley rats and the fluorescence detected 1 h later by confocal microscopy.
      Within 1 h there was rapid uptake into cells close to the site of injection and
      into brain parenchyma around the third and lateral ventricles. To test that the
      AS-ODN had reduced AT1 receptors, binding studies were carried out on membranes
      from hypothalamic tissue. There was a modest (approximately 20%) but significant
      (P < .05) decrease in the AT1 receptor binding after 25 microm or 50 microm AS
      ODN. AT2 receptors were not altered by the AS-ODN, indicating its specificity for
      the AT1 receptor. The small decrease in receptor binding, relative to its large
      effect on blood pressure, is discussed in terms of the AT1 receptor life cycle.
      The mechanism for the long action of a single AS-ODN injection is hypothesized as
      resulting from the persistence of AS-ODN in the nucleus, preventing transport of
      the mRNA into the cytoplasm.

PMID- 9160783
TI  - Renal P450 metabolites of arachidonic acid and the development of hypertension in
      Dahl salt-sensitive rats.
AB  - Renal transplantation studies indicate that some form of renal dysfunction
      underlies the development of hypertension in Dahl salt-sensitive (S) rats;
      however, the factors responsible for altering kidney function remain to be
      determined. Previous studies have indicated that Dahl S rats require a higher
      renal perfusion pressure to excrete the same amount of sodium and water as
      normotensive rats and that this is due largely to an elevation in Cl- transport
      in the thick ascending limb of the loop of Henle. There are now five lines of
      evidence that suggest an abnormality in the renal metabolism of arachidonic acid
      by enzymes of the P4504A family may contribute to the increase in loop Cl-
      transport and the development of hypertension in Dahl S rats. In this regard, the
      formation of 20-HETE and the levels of P4504A protein are reduced in the outer
      medulla of Dahl S rats. Perfusion of the loop of Henle of Dahl S rats with
      exogenous 20-HETE normalizes the elevated loop Cl- transport. In addition, a
      genetic marker in the P4504A2 gene, which encodes for the enzyme that makes 20
      HETE, cosegregates with the development of hypertension in an F2 cross of Dahl S
      and Lewis rats. Finally, induction of renal production of 20-HETE with clofibrate
      prevents the development of hypertension in Dahl S rats and inhibition of renal
      20-HETE formation produces hypertension in Lewis rats fed a high salt diet. These
      results implicate the CYP4A2 locus as a candidate gene that contributes to the
      alterations in renal function and the development of hypertension in Dahl S rats.

PMID- 9160784
TI  - Diuretics, potassium, and ventricular ectopy.

PMID- 9160785
TI  - Urinary kallikrein in Dahl-Iwai salt-sensitive and -resistant rats.
AB  - This study was designed to evaluate the differences between the renal kallikrein
      in newly established Dahl-Iwai rats under salt loading and that of Sprague-Dawley
      rats (SD). Urinary kallikrein quantity and activity was markedly lower in Dahl
      Iwai rats than in SD even during the control period. Moreover, kallikrein
      quantity and activity in Dahl-Iwai salt-sensitive rats (SS) were clearly
      diminished in comparison with salt-resistant rats (SR). The kallikrein activity/
      quantity ratio was also lower in SS and SR than in SD during the control period.
      After salt loading, systolic blood pressure increased only in SS. Kallikrein
      activity in SS and SR, and kallikrein quantity in SS were increased, whereas
      those in SD did not change. Although the kallikrein activity/quantity ratio in SR
      reached the same level in SD after salt loading, that in SS was lower throughout
      the experiment. These results suggest that Dahl-Iwai rats are less able
      hereditarily to produce renal kallikrein and that there may exist structurally
      abnormal kallikrein that may have a lower activity. Different kinetics of renal
      kallikrein between SS and SR by salt loading might be explained by kallikrein
      inhibitors or abnormal kallikrein or nonkallikrein kininogenase. These different
      kinetics of renal kallikrein may play some role on blood pressure elevation in
      SS.

PMID- 9160786
TI  - Transition from compensatory hypertrophy to dilated failing left ventricle in
      Dahl-Iwai salt-sensitive rats.

PMID- 9160787
TI  - Long-term infusion of kallikrein attenuates renal injury in Dahl salt-sensitive
      rats.
AB  - We investigated whether long-term infusion of kallikrein would attenuate renal
      injury in salt-induced hypertension in Dahl salt-sensitive (Dahl S) rats. A
      subdepressor dose of purified rat urinary kallikrein (RUK) (700 ng/day) was
      infused intravenously by an osmotic minipump for 4 weeks in male Dahl S rats fed
      a high-salt (2% NaCl) diet. This dose did not affect the time-dependent elevation
      of blood pressure. However, urinary protein excretion was significantly
      decreased, and the glomerular filtration rate was increased. These beneficial
      effects were reflected morphologically by an attenuation of the
      glomerulosclerotic lesions and tubular injury seen in the hypertensive Dahl S
      rats. The kallikrein infusion increased the urinary excretion of bradykinin and
      stimulated the excretion of cyclic GMP, suggesting that the kallikrein-kinin
      prostaglandin and nitric oxide axes were enhanced by the RUK infusion. The
      alterations induced by such infusion were potentiated by the concomitant
      administration of the angiotensin converting enzyme inhibitor alacepril. These
      studies indicated that long-term replacement with rat tissue kallikrein
      attenuates renal injury in hypertensive Dahl S rats, and this is probably
      mediated by an enhanced function of the kallikrein-kinin-prostaglandin and nitric
      oxide systems.

PMID- 9160788
TI  - Dietary L-arginine supplementation normalizes regional blood flow in Dahl-Iwai
      salt-sensitive rats.
AB  - We performed the present study to determine 1) whether different organs undergo
      similar increase in vascular resistance in Dahl-Iwai salt-sensitive (S) rats, and
      2) the effects of chronic oral L-arginine supplementation on the regional
      hemodynamics in S rats. Male 6 week old S rats and Dahl-Iwai salt-resistant (R)
      rats were maintained on an 8% NaCl chow for 4 weeks. One group (S or R rats) was
      maintained on tap water and the other group (S/Arg) of S rats received tap water
      containing L-arginine at a concentration of 1.5%. Organ blood flow and cardiac
      output were measured with microspheres in the conscious condition. Concerning
      regional hemodynamics, the flow rate of the kidney was lower in S rats than in R
      rats, but there were no differences between S and R rats in the flow rates of the
      brain, heart, lung, liver, spleen, intestine, skeletal muscle and skin. The flow
      rate of the kidney in S/Arg rats was maintained at a higher level as compared to
      that of S rats. Urinary excretion of protein and albumin in S/Arg rats was
      significantly suppressed when compared to S rats. Thus, the supplementation of L
      arginine normalized the abnormality of renal hemodynamics accompanying salt
      induced hypertension. It is suggested that the disturbance in the production of
      nitric oxide may induce salt-sensitive hypertension and the abnormality of renal
      hemodynamics in the S rats.

PMID- 9160789
TI  - Genetic profiles of newly inbred Dahl/Iwai salt-sensitive and salt-resistant
      rats.
AB  - Dahl-Iwai salt-sensitive (S) and salt-resistant (R) rat strains were established
      as inbred strains at Brookhaven National Laboratory, NY, and were introduced into
      Eisai Co., Ltd., Japan, and designated DIS/Eis and DIR/Eis. To examine whether
      there are different allele distributions among the substrains of inbred Dahl S
      and R rats, we determined biochemical and immunological alleles of DIS/Eis and
      DIR/Eis, and SS/Sea and SR/Sea, which were derived from SS/Jr and SR/Jr, which
      were developed by Rapp and Dene. Several differences of allele distribution were
      observed, indicating that the substrains have different genetic backgrounds. The
      phenotypic differences between the substrains, such as the severity of the
      hypertension induced, could be ascribed to the different genetic backgrounds.

PMID- 9160791
TI  - The implication of renin-angiotensin system on renal injury seen in Dahl salt
      sensitive rats.
AB  - Angiotensin II (Ang II) progresses to remodeling of the cardiovascular system
      through nonhemodynamic as well as hemodynamic effects. There have been few data
      in vivo on whether subpressor concentration of Ang II is exerted to injure
      directly the cardiovascular system in hypertension. To test this hypothesis, we
      investigated, using Dahl salt-sensitive (Dahl S) rats, whether subpressor dose of
      Ang II progresses to cardiovascular injury observed in salt-induced hypertension.
      Recent studies have provided evidence that renin-angiotensin inhibition protects
      against renovascular injury in human hypertension as well as in experimental
      animals. Particularly in the case of Dahl salt-sensitive rats, a genetic model of
      volume-dependent hypertension in humans, they are likely to develop more severe
      arterial and renal injuries than those seen in spontaneously hypertensive rats
      with similar blood pressure levels. The mechanism of the susceptibility to
      hypertensive injuries is uncertain; however, renin-angiotensin inhibition
      significantly improved morphologic and functional injuries in the kidney of Dahl
      S rats. Conversely, subpressor dose of Ang II infusion exacerbated renal function
      and progressed to glomerulosclerotic lesions. Alterations of Ang II concentration
      in physiologic range influenced morphologic and functional injuries in Dahl S
      rats. Multivariate analysis revealed that activity of the renin-angiotensin
      system is an independent risk factor to glomerular injury in salt-induced
      hypertension. These data are in favor of the therapeutic strategy in human
      hypertension that inhibition of renin-angiotensin system is of value to produce
      beneficial effects of blood pressure reduction on organ injuries.

PMID- 9160790
TI  - Analysis of molecular heterogeneity of Dahl/Iwai salt-sensitive rats and salt
      resistant rats.
AB  - Molecular evidence, using DNA fingerprint analyses, of extensive genetic
      heterogeneity between spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats
      (WKY) and even within some of the WKY colonies has been reported. Thus we
      investigated the genetic relations between Dahl S and R rats newly inbred by Dr.
      Iwai. Genomic DNA was isolated from the liver of four Dahl S and four Dahl R
      rats, digested with the restriction enzyme HinfI or AluI, and separated in 1.2%
      agarose gel by electrophoresis. Then, DNA fingerprinting was performed by
      Southern blot analysis using the human myoglobin 33.6 minisatellite probe. Bands
      were detected in an alkaline phosphatase reaction system. Within the same
      strains, there was no heterogeneity of these fingerprinting patterns. The S and R
      rats shared 82% of the bands in the HinfI-digested DNA and 93% of those in the
      AluI-digested DNA. These shared values were much greater than the reported value
      (54%) between SHR and WKY from Charles River Laboratories. These newly inbred
      Dahl S and R rats may be appropriate, although still limited, experimental
      animals for investigating the pathophysiology of salt-sensitive hypertension.

PMID- 9160792
TI  - Effect of cilazapril and salt on Ca2+ extrusion in arterial smooth muscle of Dahl
      rats.
AB  - We examined effects of salt and cilazapril on the Ca pump and Na/Ca exchange
      system in arterial smooth muscle of Dahl salt-sensitive (DS) rats. Twenty-four DS
      rats were assigned to four groups. H and H+ rats were fed a high salt diet; L-
      and L+ rats were fed a low salt diet. H+ and L+ were administered cilazapril.
      Aortic rings were superfused with physiologic saline and isometric tension was
      measured. Relaxation of low Na+-induced contraction was promoted by the removal
      of external Ca. Cilazapril significantly decreased blood pressure in both the
      high and low salt diet groups. The inhibition of renin-angiotensin system by
      cilazapril showed that Ca extrusion by ATP-driven Ca pump was decreased by salt
      loading, and that Ca extrusion by Na/Ca exchange was increased by salt loading.
      There was a negative correlation between Ca extrusion by Ca pump and blood
      pressure, and a positive correlation between Ca extrusion by Na/Ca exchange and
      blood pressure. These results suggest that the decrease of Ca2+ extrusion by ATP
      driven Ca pump resulting from a high salt diet might lead to an elevation in the
      concentration of cellular Ca2+ and contribute to the mechanism of hypertension in
      DS rats, and that Ca2+ extrusion by the Na/Ca exchange might be increased in
      compensation for an increase in cellular Ca2+ concentration on the high salt
      diet.

PMID- 9160793
TI  - Enhanced electrical activity in mesenteric arteries from salt-loaded Dahl salt
      sensitive rats: actions of prostaglandin H2 on membrane channels.
AB  - Salt loading increases blood pressure in Dahl salt-sensitive (Dahl S) rats. We
      have previously shown that the mesenteric artery of salt-loaded Dahl S rats
      exhibits enhanced electrical activity that is corrected by a cycloxygenase
      inhibitor, indomethacin. Prostaglandin H2 (PGH2) is a product of cycloxygenase
      that is known as an intrinsic vasoconstricting factor in spontaneously
      hypertensive rats. Our hypothesis is that tissue production of PGH2 would be
      involved in the enhanced electrical activity of arteries from salt-loaded Dahl S
      rats. In the present study, to clarify this possibility, we evaluated the actions
      of PGH2 on membrane channels in arterial cells from Dahl S rats. Membrane
      currents were recorded by whole-cell voltage clamp technique in single smooth
      muscle cells from the mesenteric artery. Application of PGH2 evoked an inward
      current that was mainly dependent on extracellular Na+ in the physiological
      extracellular solution. When high Ba2+ solution was used for the extracellular
      solution, PGH2 also evoked the inward current, suggesting that a divalent cation,
      such as Ba2+ or Ca2+, could permeate the PGH2-activated channels. In contrast,
      the L-type Ca2+ channel currents were not enhanced by the application of PGH2.
      The present results suggest that production of PGH2 contributes to the enhanced
      electrical activity by activating cation-permeable channels and depolarizing the
      membrane potential. PGH2 also directly stimulates the Ca2+ influx by activating
      Ca2+ permeable channels.

PMID- 9160794
TI  - Vitamin E ameliorates the renal injury of Dahl salt-sensitive rats.
AB  - Recently, hyperlipidemia as well as hypertension has been observed in Dahl salt
      sensitive (S) rats. In this study, to investigate whether the lipid abnormality
      is involved in the renal injury of Dahl S rats, we examined the effect of vitamin
      E on glomerular sclerosis, as vitamin E is an inhibitor of lipid oxidation. Dahl
      S rats were given a high salt diet (8% NaCl) containing either normal vitamin E
      (2 mg/100 g) or high vitamin E (50 mg/100 g) for 4 weeks. Dahl salt-resistant (R)
      rats were given a high salt and normal vitamin E diet. The blood pressure in the
      Dahl rats increased and was not suppressed by the vitamin E supplement. Serum
      cholesterol and triglycerides in Dahl S rats were higher than in Dahl R rats at
      both 0 and 4 weeks. Vitamin E lowered the serum cholesterol level in Dahl S rats
      at 4 weeks (126 +/- 5 v 150 +/- 12 mg/dL, P < .01). Urinary protein excretion and
      serum creatinine increased in Dahl S rats, and vitamin E inhibited the increases
      significantly (urinary protein, 70.7 +/- 0.9 v 178.0 +/- 8.8 mg/day, P < .01;
      serum creatinine, 0.45 +/- 0.02 v 0.63 +/- 0.05 mg/dL, P < .01). Serum lipid
      peroxide (LPO) was higher in Dahl S rats than in Dahl R rats, and vitamin E
      lowered LPO in Dahl S rats (2.10 +/- 0.03 v 2.70 +/- 0.04 nmol/mL, P < .01). In
      the histologic study, sclerosing score (SS) of glomeruli, which represents the
      degree of glomerulosclerosis semiquantitatively, was higher in Dahl S rats than
      in Dahl R rats. Vitamin E lowered SS (114 +/- 3 v 157 +/- 6, P < .01) and
      ameliorated arterial injuries such as medial thickness with partial necrosis and
      severe fibrinoid proliferation with inflammatory cell infiltration. In all rats,
      SS was strongly correlated with urinary protein (r = 0.93, P < .01), serum
      cholesterol (r = 0.86, P < .01), and serum LPO (r = 0.89, P < .01). These results
      suggest that the renal injury in Dahl S rats is caused not only by hypertension
      but also by hyperlipidemia. Therefore, vitamin E might ameliorate the renal
      damage by inhibiting the oxidation of lipids.

PMID- 9160795
TI  - The transition to failure in the spontaneously hypertensive rat.

PMID- 9160796
TI  - Allele frequency of ADH2 and ALDH2 among Brazilians of different ethnic groups.
AB  - We determined the genotypes of the alcohol dehydrogenase (ALDH) and aldehyde
      dehydrogenase (ALDH2) loci of different ethnic groups living in Brazil, using
      saliva DNA amplified by PCR and allele-specific oligonucleotides. Self-reports of
      flushing reaction after drinking were also studied. The allelic frequencies of
      ADH2 and ALDH2 were found to be lower than those reported other authors, which
      might be a result of the admixture origin of the Brazilian population.
      Variability in facial flushing reaction suggests that other factors play a role
      in the expression of alcohol-induced flushing.

PMID- 9160797
TI  - The effect of acute ethanol (EtOH) exposure on protein kinase C (PKC) activity in
      anterior pituitary.
AB  - Alterations in the protein kinase C (PKC) pathway may interrupt anterior
      pituitary luteinizing hormone (LH) synthesis and/or secretion, which may impair
      normal reproductive function. Work by our laboratory and others has shown that
      EtOH has profound deleterious effects on the regulation of the hypothalamic
      pituitary-gonadal (HPG) axis. The present study focuses on PKC translocation from
      the cytosol to the membrane of anterior pituitary after acute EtOH exposure.
      Serum levels of LH were measured at three time points (15, 30, and 90 min) after
      an IP injection of either saline or 3 g/kg EtOH in adult castrated male rats. LH
      levels dropped significantly (p < 0.03) in EtOH-injected compared to saline
      injected control animals. In the same animals, EtOH significantly suppressed PKC
      localization at its active site at the pituitary cell membrane (p < 0.05). These
      findings suggest that the mechanism of EtOH's suppression of LH is mediated, at
      least in part, through a decrease in PKC translocation to the anterior pituitary
      cell membrane.

PMID- 9160799
TI  - Taste reactivity in high-alcohol-sensitive and low-alcohol-sensitive rats.
AB  - High, low, and control alcohol-sensitive (HAS, LAS, CAS, respectively) rats were
      tested for their perception of the taste of alcohol using the taste reactivity
      test. Reactivity tests with a single concentration of sucrose and quinine were
      also done. After initial taste reactivity, all rats were tested for alcohol
      consumption in a standard two-bottle test (water in the second bottle).
      Postconsumption taste reactivity tests completed the experiment. Results
      indicated that HAS, LAS, and CAS rats did not differ significantly in their taste
      reactivity response to a range of alcohol concentrations (5-40%), nor did they
      differ significantly in response to sucrose or quinine. Reactivity responses were
      similar for each group before and after the consumption tests. Despite the lack
      of line differences in taste reactivity, HAS and LAS rats consumed significantly
      less alcohol than the CAS rats during the two-bottle access tests. The present
      results are in contrast to research done with rats selectively bred for alcohol
      consumption (Alcohol Preferring and Nonpreferring rats, High Alcohol Drinking and
      Low Alcohol Drinking rats), which exhibit clear line differences in patterns of
      reactivity changes following alcohol access. The selection phenotype of alcohol
      sensitivity appears to be independent of rats' behavioral response to the taste
      of alcohol.

PMID- 9160798
TI  - Putative oxidative metabolites of 1-methyl-6-hydroxy-1,2,3,4-tetrahydro-beta
      carboline of potential relevance to the addictive and neurodegenerative
      consequences of ethanol abuse.
AB  - Ethanol is metabolized in the brain by catalase/H2O2 to yield acetaldehyde and by
      an ethanol-inducible form of cytochrome P450 (P450 IIE1) in a reaction that
      yields oxygen radicals. Within the cytoplasm of serotonergic axon terminals these
      metabolic pathways together provide conditions for the endogenous synthesis of 1
      methyl-6-hydroxy-1,2,3,4-tetrahydro-beta-carboline (1), by reaction of
      acetaldehyde with unbound 5-hydroxytryptamine (5-HT), and for the oxygen radical
      mediated oxidation of this alkaloid. The major initial product of the hydroxyl
      radical (HO.)-mediated oxidation of 1 in the presence of free glutathione (GSH),
      a constituent of nerve terminals and axons, is 8-S-glutathionyl-1-methyl-1,2,3,4
      tetrahydro-beta-carboline-5,6-dione (6). When administered into the brains of
      mice, 6 is a potent toxin (LD50 = 2.9 microg) and evokes episodes of
      hyperactivity and tremor. Compound 6 binds at the GABA(B) receptor and evokes
      elevated release and turnover of several neurotransmitters. Furthermore, the
      GABA(B) receptor antagonist phaclofen attenuates the behavioral response caused
      by intracerebral administration of 6. These observations suggest that 6 might be
      an inverse agonist at the GABA(B) receptor site. Accordingly, it is speculated
      that ethanol drinking might potentiate formation of 6 that contributes to
      elevated release of several neurotransmitters including dopamine (DA) and
      endogenous opioids in regions of the brain innervated by serotonergic axon
      terminals. Subsequent interactions of DA and opioids with their receptors might
      be related to the initial development of dependence on ethanol. Redox cycling of
      6 (and of several putative secondary metabolites) in the presence of
      intraneuronal antioxidants and molecular oxygen to produce elevated fluxes of
      cytotoxic reduced oxygen species might contribute to the degeneration of
      serotonergic pathways. Low levels of 5-HT in certain brain regions of the rat
      predisposes these animals to drink or augments drinking. Accordingly, 6, formed
      as a result of ethanol metabolism in the cytoplasm of certain serotonergic axon
      terminals, might contribute to the initial development of dependence on ethanol,
      by mediating DA and opioid release, and long-term preference and addiction to the
      fluid as a result of the progressive degeneration of these neurons.

PMID- 9160800
TI  - Effects of prenatal ethanol exposure on hippocampal theta activity in the rat.
AB  - This study examined the effects of prenatal ethanol exposure on hippocampal theta
      activity in adult rats. Subjects were randomly selected from four prenatal
      treatment conditions: untreated, 0, 3, or 5 g/kg/day ethanol. At approximately 90
      days of age, all subjects were surgically implanted with a bipolar electrode in
      the CA1 region of the hippocampus. Four epochs of hippocampal theta rhythm
      activity were recorded while the subjects were moving and four more while still,
      and a normalized theta score was computed and compared among groups. The 5 g/kg
      male group demonstrated a significantly higher theta score than controls,
      indicating either an increase in type I (movement-associated) theta and/or a
      decrease in type II (information-processing) theta activity. These results are
      consistent with prior reports that prenatal ethanol exposure alters hippocampal
      function and support clinical indications that monitoring the EEG of children may
      prove to be useful in the diagnosis of fetal alcohol syndrome and/or the
      detection of alcohol-related birth defects.

PMID- 9160801
TI  - The role of the blood-brain barrier transporter PTS-1 in regulating
      concentrations of methionine enkephalin in blood and brain.
AB  - Previous studies have suggested that peptide transport system (PTS)-1, a
      saturable efflux system from brain to blood, regulates the concentration in the
      brain of methionine enkephalin (Met-Enk), an opiate peptide related to the
      drinking of ethanol in mice. We determined the relationship of PTS-1 to
      concentrations of immunoreactive Met-Enk in plasma and whole brain in eight
      randomly selected strains of mice. An active PTS-1 system could be demonstrated
      in five of the eight strains. In those five strains, faster efflux rates due to
      PTS-1 correlated with higher concentrations of Met-Enk in brain and plasma. These
      concentrations of Met-Enk in brain and plasma were positively correlated in the
      five strains in which PTS-1 was demonstrable and were inversely correlated in the
      three strains in which PTS-1 was not demonstrable. The results are consistent
      with previous observations indicating that the chronic level of brain Met-Enk can
      set the level of activity of PTS-1 and that, once set, PTS-1 can play a major
      role in determining the concentrations of Met-Enk in brain and blood.

PMID- 9160802
TI  - Ethanol intake after chronic intoxication by inhalation of ethanol vapour in
      rats: behavioural dependence.
AB  - In Wistar rats, which practically avoid ethanol when naive, it is possible to
      induce a large ethanol intake in a free-choice situation after chronic
      intoxication by ethanol vapour. In this study, we evaluated the ethanol intake of
      chronically intoxicated and control rats. The ethanol intake was increased in
      intoxicated animals but the intensity of the response varied according to
      individuals without any clear relation to the level of the intoxication. The
      results clearly showed in intoxicated animals two kinds of responders: alcohol
      nonpreferring (27/95) and alcohol-preferring rats (68/95). In the alcohol
      preferring rats, ethanol intoxication had induced an alcohol drinking-dependent
      behaviour; about 75% of the animals of this group drank more than 7 g/kg b.wt.
      per day and could be considered as behaviourally dependent on alcohol.
      Furthermore, this group presents most of the criteria of alcoholism that an
      animal model should ideally satisfy.

PMID- 9160803
TI  - Biphasic in vivo immune function after low- versus high-dose alcohol consumption.
AB  - A series of experiments was performed to assess the alterations in immune status
      in vivo that are associated with differences in the amount and duration of
      ethanol intake. Using a nonspecific delayed cutaneous hypersensitivity-like
      response to the intradermal injection of phytohemagglutinin, the area of
      induration (skin test response) was significantly enhanced (p = 0.008) after low
      dose ethanol (0.5 g/kg) administered daily by gastric gavage for 5 days. High
      dose ethanol (6.0 g/kg) significantly diminished this response (p = 0.03). Using
      an experimental model of Mycobacterium bovis hepatitis, the host immune response
      was also altered in a biphasic manner after chronic, 28-day ethanol consumption.
      With this model 0.43 +/- 0.03 g/kg/day (mean +/- SEM) of ethanol (low dose) was
      associated with a 40% improvement in the removal of the organisms from liver
      tissue (p = 0.002). High dose (12.1 +/- 0.5 g/kg/day) impaired removal, resulting
      in a 55% increase in the number of viable organisms (p = 0.001). The levels of
      three cytokines, MIF, TNF-alpha, and IL-2, known to be involved in the modulation
      of the host response to mycobacterial infections, were measured in sera after the
      infection. The serum levels of these cytokines in response to infection did not
      correlate with this biphasic response to different alcohol dose levels.

PMID- 9160804
TI  - The paradoxical hedonic valence of acute ethanol withdrawal (hangover) states in
      rats: place and taste conditioning.
AB  - The hedonic valence of EtOH's delayed effects, usually referred to as "hangover,"
      was assessed 18 h after a 4 g/kg injection using both place and taste learning
      tasks. In the place conditioning task two CS-,CS+ intervals were used (48 h and
      144 h); within each treatment interval, experimentally induced "hangover" was
      paired with the initially nonpreferred conditioning compartment for half of the
      experimental group (N = 10 rats) and with the initially preferred conditioning
      compartment for the half (N = 10 rats). Saline injections were paired with
      placement in the alternate conditioning compartment. A third group (N = 10 rats)
      was conditioned with milliliter equivalent volumes of saline on both sides. A
      conditioned place preference was conditioned with the hangover state-induced
      interoceptive stimuli. Attempts were made to taste condition 24 rats with the
      interoceptive stimulus attributes of hangover. Experimentally induced hangover
      was associated with an adipsogenic state, defined as a significant decline in
      voluntary intake of both saccharin and water, which prevented taste conditioning.

PMID- 9160805
TI  - Effects of chronic ethanol ingestion on mid-latency auditory evoked potentials
      depend on length of exposure.
AB  - We hypothesized that chronic ethanol ingestion is associated with modifications
      in components of mid-latency auditory evoked potentials (MAEPs). To test this,
      male Long Evans rats were administered 10% ethanol in drinking water as the sole
      fluid source for 3, 6, or 9 months. MAEPs were obtained and compared to age
      matched control groups. MAEPs were obtained from additional rats after 4 weeks of
      abstinence. Data were obtained for varying frequencies (4, 8, 16, 24, 32 kHz) and
      intensities (65, 75, 85 dB SPL). Three months of ethanol exposure was associated
      with increased latencies and amplitudes of Na and Pa. MAEP components recovered
      and returned to control values after 4 weeks' abstinence following 3 months of
      EtOH exposure. Few significant differences were observed in the ethanol-treated
      or abstinent group after 6 months' exposure. However, 9 months of ethanol
      exposure revealed a significant increase in latencies and decrease in amplitudes
      of both Na and Pa components. After 4 weeks of abstinence, the Na and Pa
      component peak latencies appeared earlier than age-matched controls. The Na and
      Pa peak amplitudes were slightly greater than the ethanol-treated group; however,
      they did not recover to control values. These findings suggest that chronic
      ethanol consumption may produce time-dependent structural and/or neurochemical
      alterations in substrates for cortical information processing, which may be
      irreversible. In the present paradigm, this irreversibility may occur after 6 or
      more months of ethanol intake, and may be detected with the use of MAEPs.

PMID- 9160806
TI  - Dopaminergic and opiate agonists and antagonists differentially decrease multiple
      schedule responding maintained by sucrose/ethanol and sucrose.
AB  - Similar neurobiological mechanisms are hypothesized to influence ethanol- and
      food-related reinforcement processes. This study examined the ability of
      compounds with dopaminergic or opiate activity to selectively alter responding
      maintained by a sucrose/ethanol solution in comparison to a sucrose solution.
      Long-Evans rats were trained to press a lever using 5% sucrose/10% ethanol and 5%
      sucrose as the reinforcers on a multiple Fixed Ratio 4 Fixed Ratio 4 schedule of
      reinforcement. When stable responding was established, the effects of
      intraperitoneally administered amphetamine (0.0-3.0 mg/kg), haloperidol (0.0-1.0
      mg/kg), morphine (0.0-10.0 mg/kg), and naloxone (0.0-10.0 mg/kg) were examined on
      total session reinforcer presentation and presentation of each reinforcer within
      individual multiple schedule components. Prior to drug treatment, the total
      number of reinforcer presentations of the sucrose/ethanol solution was
      significantly greater than sucrose reinforcer presentations, suggesting the
      sucrose/ethanol solution was a more efficacious reinforcer. All agents
      administered decreased responding maintained by sucrose/ethanol and sucrose. The
      dose-effect curves for sucrose/ethanol were shifted to the left compared to
      sucrose, suggesting that although the compounds did not selectively impact
      sucrose/ethanol-maintained responding, sucrose/ethanol-maintained responding was
      more sensitive to the effects of these compounds.

PMID- 9160807
TI  - Influence of methanol and its metabolites on the activity of alpha1-antitrypsin.
AB  - Among methanol and its metabolites, formaldehyde was found to have the strongest
      inactivating effect on the activity of alpha1-antitrypsin preparation and
      inhibitor existing in blood serum. The influence of formaldehyde on the activity
      of serum alpha1-antitrypsin is lower in comparison with purified inhibitor.
      alpha1-Antitrypsin modified by formaldehyde inactivates the trypsin in its action
      on the BAPA to a smaller degree than on the hemoglobin. The effective
      formaldehyde concentration in the case of the BAPA is about 64 mM and in the case
      of the hemoglobin is about 256 mM. The significant inhibitory effect of methanol
      on alpha1-antitrypsin appears only at a high concentration of this compound.
      Formate does not decrease alpha1-antitrypsin activity. In people intoxicated with
      methanol, alpha1-antitrypsin activity decreases, whereas the content of this
      inhibitor does not change.

PMID- 9160808
TI  - Response of cardiac antioxidant system to alcohol and exercise training in the
      rat.
AB  - Recent evidence has shown that alcohol as well as exercise induces oxidative
      stress. However, the combination of both on the cardiac antioxidant system is not
      known. This study investigates the interactive effects of exercise training and
      chronic ethanol consumption on the antioxidant system of the rat heart. Male
      Fisher-344 rats were treated as follows: 1) sedentary control (SC); 2) exercise
      training (ET) for 6.5 weeks; 3) ethanol (2 g/kg, PO) for 6.5 weeks, and 4) ET
      plus ethanol for 6.5 weeks. Rats were sacrificed and hearts were isolated.
      Glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD),
      catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and
      lipid peroxidation (MDA) were determined in heart tissues. SOD and GSH-Px
      activities were significantly increased 118% and 148% of SC, respectively, due to
      ET. GSH level increased 118% of SC in ET rats. GSH-Px activity increased 118% of
      SC whereas SOD activity and CuZn-SOD protein level and GR activity decreased 87%,
      71%, and 90% of SC due to chronic ethanol administration. GSH level decreased 87%
      of SC and lipid peroxidation increased 149% of SC due to ethanol consumption. GSH
      Px activity and GSH levels increased 143% and 130% of SC due to combination of ET
      and ethanol. This study suggests that ET and chronic ethanol ingestion augments
      the antioxidant enzyme activity and GSH levels in the heart. This combination
      reduced the extent of ethanol-induced lipid peroxidation. The data suggest that
      ET may reduce the extent of the damage caused by ethanol consumption on the
      myocardium.

PMID- 9160809
TI  - Age-related decreases in chromium levels in 51,665 hair, sweat, and serum samples
      from 40,872 patients--implications for the prevention of cardiovascular disease
      and type II diabetes mellitus.
AB  - This report shows, for the first time using modern analytical techniques, highly
      significant age-related decreases in chromium levels in 51,665 hair, sweat, and
      serum samples obtained from 40,872 patients referred by their physicians to an
      independent medical research clinic and laboratory (r = -.598 to -.762, P < .0001
      for all correlations). Males were found to have significantly lower mean chromium
      levels than females (P < .05 to .0001). There was good correlation between
      chromium levels in hair, sweat, and serum (r = .536 to .729, P < .0001 for all
      correlations), indicating that hair and sweat chromium levels are valid additions
      to the serum levels in assessing chromium status. Chromium measurements in sweat,
      hair, and serum were performed using graphite furnace atomic absorption
      spectrophotometry. The influences that age-related decreases in chromium levels
      might have on increasing the risk to develop age-related impaired glucose
      metabolism, disordered lipid metabolism, coronary heart disease,
      arteriosclerosis, and type II diabetes mellitus are outlined, and the role that
      refined carbohydrates play in the development of compromised chromium status is
      presented.

PMID- 9160810
TI  - Fish-eye disease: structural and in vivo metabolic abnormalities of high-density
      lipoproteins.
AB  - Fish-eye disease (FED) in humans is characterized by corneal opacities and
      markedly decreased plasma concentrations of high-density lipoprotein (HDL)
      cholesterol, apolipoprotein (apo) AI, and apo All, but no tendency to precocious
      atherosclerosis is present. To elucidate this paradox, the structure of HDL, the
      potential of serum to promote cholesterol efflux from cultured cells, and the in
      vivo metabolism of HDL were examined in a 53-year-old woman with a FED syndrome
      in association with a markedly decreased lecithin:cholesterol acyltransferase
      (LCAT) activity in HDL due to a mutation of the LCAT gene (Arg158 --> Cys). HDLs
      isolated by ultracentrifugation were small and enriched in unesterified
      cholesterol and phospholipids at the expense of cholesteryl esters and proteins.
      The apolipoprotein content showed an enrichment in apo E and apo AIV, whereas apo
      AI and apo All were dramatically reduced. Sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE) and immunoblotting using specific antibodies
      showed that the apo E was free or covalently bound to apo All. These particles
      analyzed by electron microscopy were small and round lipoproteins with a size
      similar to the smallest fraction of normal HDL3. The potential capacity of the
      serum to promote efflux from the cells was approximately 40% of control serum
      levels, but FED HDLs were as efficient as control HDLs in promoting cholesterol
      efflux from cells. To assess the metabolism of HDL apolipoproteins, in vivo
      apolipoprotein kinetic studies were performed using endogenous labeling
      techniques in the patient with FED and three control subjects. All subjects were
      administered D3-labeled leucine by primed constant infusion for up to 10 hours.
      The fractional synthetic rates (FSRs) of apo AI and apo All in the patient were
      0.674 and 0.594 per day, clearly higher than in controls, 0.210 +/- 0.053 and
      0.148 +/- 0.014 per day for apo AI and apo All, respectively. Apo AI and apo All
      production rates in the patient with FED were normal, 11.32 and 2.62 mg/kg x d,
      respectively, as compared with those in normal subjects, 11.45 +/- 1.23 and 2.68
      +/- 0.17 mg/kg x d. These data established that hypoalphalipoproteinemia in FED
      was caused by marked hypercatabolism of apo AI and apo All. This hypercatabolism
      could be the consequence of structural abnormalities due to the selective LCAT
      deficiency. In conclusion, two steps of reverse cholesterol transport,
      cholesterol efflux and apo-HDL metabolism, appeared particularly efficient. This
      efficiency could participate in the absence of premature atherosclerosis in FED
      patients as regards the low HDL level.

PMID- 9160811
TI  - Intravenous glucose tolerance test-derived glucose effectiveness in bulimia
      nervosa.
AB  - The aim of the present study was to estimate insulin secretion, insulin
      sensitivity (SI), and glucose effectiveness at basal insulin (SG) in subjects
      with bulimia nervosa. Eight bulimic patients and eight age-, body mass index-,
      and sex-matched healthy control subjects without a family history of diabetes
      were studied. The subjects all had normal glucose tolerance. They underwent a
      modified frequently sampled intravenous glucose tolerance test; glucose (300
      mg/kg body weight) was administered, and insulin (4 mU/kg body weight/min) was
      infused from 20 to 25 minutes after administration of glucose. SI and SG were
      estimated by Bergman's minimal model method. Basal insulin (27 +/- 3 v 45 +/- 3
      pmol/L) was significantly lower in bulimic patients than in normal controls (P <
      .05), but basal glucose was similar between the two groups (4.5 +/- 0.1 v 4.9 +/-
      0.1 mmol/L, P > .05). The glucose disappearance rate (KG) and acute insulin
      response to glucose estimated by the intravenous glucose tolerance test
      (AIR(glucose)) were similar between the two groups (KG, 1.35 +/- 0.29 v 2.20 +/-
      0.21 min(-1), P > .05; AIR(glucose), 2,920 +/- 547 v 2,368 +/- 367 pmol/L x min,
      P > .05). No significant difference was observed in SI between the two groups
      (1.34 +/- 0.18 v 1.25 +/- 0.20 x 10(-4) x min(-1) x pmol/L(-1), P > .05). On the
      other hand, glucose effectiveness at basal (SG) and zero (GEZI) insulin was
      significantly diminished in comparison to normal controls (SG, 0.011 +/- 0.002 v
      0.024 +/- 0.002 min(-1), P < .01; GEZI, 0.008 +/- 0.002 v 0.017 +/- 0.003 min(
      1), P < .01). Thus, bulimic patients with normal glucose tolerance without a
      family history of diabetes were characterized by normal insulin secretion, normal
      SI, and reduced SG and GEZI.

PMID- 9160812
TI  - Endothelin production in cultured vascular smooth muscle cells--modulation by the
      atrial, brain, and C-type natriuretic peptide system.
AB  - We examined the regulatory mechanisms of endothelin-1 (ET-1) production in
      cultured rat vascular smooth muscle cells (VSMC) with a special focus on the
      roles of protein kinase C (PKC)- and cyclic guanosine-3',5'-monophosphate (GMP)
      mediated signaling systems. Effects of atrial, brain, and C-type natriuretic
      peptides (ANP, BNP, and CNP) on angiotensin II (Ang II)-, and arginine
      vasopressin (AVP)-induced production of ET-1 were examined in cultured rat aortic
      VSMC. Ang II and AVP stimulated ET-1 production in a concentration-dependent
      manner through angiotensin subtype 1 (AT1) and vasopressin subtype 1 (V1)
      receptors, respectively. The stimulatory effects of Ang II and AVP were markedly
      abolished in PKC-depleted cells. Rat ANP (1-28), rat BNP-45, and rat CNP-22
      potently inhibited Ang II- and AVP-stimulated ET-1 production in a concentration
      dependent manner, respectively. The inhibitory effect by CNP on ET-1 production
      was paralleled by an increase in the cellular level of cyclic GMR.8-Bromo cyclic
      GMP reduced the stimulated ET-1 production by Ang II and AVP. These results
      indicate that Ang II and AVP stimulate ET-1 production in cultured rat VSMC
      through AT1 and V1 receptors by a mechanism probably involving activation of PKC,
      and that ANP, BNP, and CNP inhibit this stimulated production through a cyclic
      GMP-dependent process.

PMID- 9160813
TI  - Comparative study of insulin-like growth factor-I (IGF-I) and IGF-binding protein
      3 (IGFBP-3) level and IGF-I/IGFBP-3 ratio measurements and their relationship
      with an index of clinical activity in the management of patients with acromegaly.
AB  - To evaluate the utility of measuring the serum insulin-like growth factor (IGF)
      binding protein-3 (IGFBP-3) level and the IGF-I/IGFBP-3 ratio in the management
      of acromegalic patients, we comparatively studied the basal concentration of the
      aforementioned parameters with determination of plasma IGF-I levels and an index
      of clinical activity of acromegaly in 16 newly diagnosed acromegalic patients
      (aged 34 to 64 years) before and after hypophysectomy. After adenomectomy, 10
      patients remained with "active" disease and six were "cured." Twenty-nine healthy
      sex- and age-matched volunteers were also studied. Comparison of individual
      values between untreated acromegalic patients and control subjects showed that
      none of the patients had overlapping values for IGF-I, whereas five of 16 and
      three of 16 patients had overlapping values for serum IGFBP-3 and IGF-I/IGFBP-3
      ratio, respectively. When we compared the study parameters between the patients
      who remained with active disease after adenomectomy and the controls, two of 10
      had overlapping values for IGF-I, but six of 10 and five of 10 had overlapping
      values for serum IGFBP-3 and IGF-I/IGFBP-3 ratio, respectively. Moreover,
      comparison of these parameters between cured and active patients after
      hypophysectomy showed that none had overlapping values for IGF-I, whereas three
      of six and one of six had overlapping values for serum IGFBP-3 and IGF-I/IGFBP-3
      ratio, respectively. All biochemical variables studied showed significant
      relationships with an index of clinical activity of disease. In conclusion, our
      results seem to indicate that among determinations of plasma IGF-I, serum IGFBP
      3, and the ratio IGF-I/IGFBP-3 in the evaluation of acromegalic patients,
      measurement of the plasma IGF-I level has the most discriminative value in the
      management of these patients.

PMID- 9160814
TI  - Endurance training with constant energy intake in identical twins: changes over
      time in energy expenditure and related hormones.
AB  - The effects of exercise training and of its interaction with the genotype on
      components of energy expenditure and related hormones were examined in young male
      monozygotic twins. Energy intake was maintained at the pretraining level for a 93
      day training period. The estimated net energy deficit induced by training was 244
      MJ and was associated with a 5-kg body weight loss that was almost entirely
      explained by body fat loss. Resting metabolic rate (RMR) was significantly
      decreased by 8% after training despite the preservation of fat-free mass (FFM).
      Accordingly, plasma norepinephrine (NE) concentrations, NE appearance rate, and
      plasma levels of triiodothyronine (T3), free T3, and total thyroxine (T4) were
      lower after training. The energy cost of standardized exercise was also reduced
      after the training program. A modest to significant within-twin-pair resemblance
      was observed for absolute changes in the RMR, thermic effect of food, energy cost
      of exercise, NE clearance, and plasma concentrations of thyroid hormones. These
      results suggest that when exercise training is associated with a substantial
      negative energy balance, energy expenditure and levels of related hormones are
      decreased, and this effect is partly accounted for by heredity.

PMID- 9160815
TI  - Decreased glucose tolerance, not decreased insulin sensitivity, is a maturational
      abnormality in the male offspring of a parent with early coronary artery disease.
AB  - We investigated whether the male offspring of a parent with early coronary artery
      disease (before the age of 60; n = 61) exhibit decreased insulin sensitivity
      compared with controls matched for age and body mass index (BMI) (n = 39). The
      insulin sensitivity index (S[I]) was determined by the minimal modeling method of
      Bergman from a frequently sampled intravenous glucose tolerance test with
      intravenous tolbutamide. Offspring and controls had a similar S[I], insulin
      independent glucose utilization (S[G]), first-phase insulin response (AIR[G]),
      and area under the glucose curve. When subjects were separated into two age
      groups, younger subjects aged 15 to 30 years and older subjects aged 31 to 45
      years, important differences were seen. S[G] was significantly increased in
      younger offspring compared with controls (22.8 +/- 2.3 v 16.8 +/- 2.3 x 10(-3) x
      min(-1), P < .05). Older offspring had a significantly increased area under the
      glucose curve compared with controls (18,250 +/- 322 v 17,225 +/- 347 mg/dL x
      min(-1), P < .05). Older offspring also had decreased S[I] compared with younger
      offspring (5.0 +/- 0.4 v 6.6 +/- 0.9 x 10(-4) x min(-1) x micro U/mL, P < .05),
      but this difference was eliminated after adjusting for BMI and waist to hip ratio
      (5.5 +/- 0.4 v5.8 +/- 0.9 x 10(-3) x min(-1), nonsignificant). This study does
      not support the concept that insulin resistance is an early atherogenic risk
      factor in offspring at risk for coronary disease because of their family history.
      However, it does point to the importance of maturational changes in glucose
      homeostasis in these offspring.

PMID- 9160816
TI  - Congenital adrenal hyperplasia complicated by central precocious puberty: linear
      growth during infancy and treatment with gonadotropin-releasing hormone analog.
AB  - Some children with congenital adrenal hyperplasia (CAH) develop true precocious
      puberty with early maturation of the hypothalamic-pituitary-gonadal axis. We have
      seen six such children who had the diagnosis of CAH with late initiation of
      corticosteroid treatment and/or poor compliance who developed central precocious
      puberty (CPP). These patients were treated with standard-dose hydrocortisone and
      fludrocortisone. Administration of depot leuprorelin (3.75 mg subcutaneously
      every 28 days) for 2 years or longer was effective in arresting the
      manifestations of puberty, decelerating the pretreatment growth velocity ([GV]
      10.8 +/- 1.5 v3.65 +/- 0.95 cm/yr), increasing the predicted adult height ([PAHT]
      147.5 +/- 7.8 v 153.4 +/- 8.3 cm), and decreasing the bone age to statural age
      ratio (1.26 +/- 0.13 v 1.16 +/- 0.09). Analysis of auxanological data during the
      first 2 years of life showed that linear growth was significantly accelerated and
      bone age was advanced in patients who developed CPP compared with 11 age-matched
      patients. It appears that proper glucocorticoid replacement to achieve adequate
      control of hyperandrogenemia during early life might prevent development of CPP
      in these patients. Gonadotropin-releasing hormone agonist (GnRHa) therapy can
      improve the final adult height, bringing it closer to that expected from the
      genetic potential.

PMID- 9160817
TI  - Serum concentrations of cortisone and cortisol in premature infants.
AB  - To determine the relationship between biological active cortisol and its inert
      metabolite cortisone accurately in premature infants, serum cortisone and
      cortisol concentrations were measured by reversed-phase high-performance liquid
      chromatography (HPLC) in a group of 232 premature infants and in a control group
      of 127 children and 88 adults. In the control group, serum cortisone
      concentrations were greater than serum cortisol levels during the first 2 months
      after birth; cortisol levels were higher than cortisone levels after 2 months of
      age. However, in premature infants, serum cortisone concentrations were greater
      than serum cortisol levels even after the first 2 months, and total
      concentrations of cortisone and cortisol were equal to those in controls. Results
      were then analyzed according to the equivalent gestational age of premature
      infants. Cortisone was predominant in premature infants older than 32 weeks of
      equivalent gestational age, but cortisol was higher than cortisone from
      equivalent gestational age 24 to 31 weeks. These findings suggest that the
      ability of premature infants to secrete glucocorticoids resembled that of normal
      controls. Also, the fetal zone of the cortex, which is associated with a
      predominance of cortisone, remained functional in premature infants for a longer
      time than in control infants. Our findings that in premature infants cortisone
      was predominant compared with cortisol and the sum of cortisone and cortisol was
      equal to that in the controls indicate that cortisone cannot be disregarded
      whenever the cortisol level is estimated, although cortisone itself is recognized
      to be biologically inactive. Simultaneous measurement of serum cortisone and
      cortisol concentrations is important when adrenocortical function is being
      determined, especially in premature infants.

PMID- 9160818
TI  - Apolipoprotein H levels in diabetic subjects: correlation with cholesterol
      levels.
AB  - To assess the relationship between apolipoprotein H (apo H) plasma levels and
      lipid metabolism in diabetes mellitus, we have examined the correlation between
      apo H plasma concentration and the main plasma lipid levels in 127 non-insulin
      dependent (NIDDM) and 118 insulin-dependent (IDDM) diabetes mellitus patients.
      The data are compared with those in 286 nondiabetics. Our data show a significant
      increase in plasma apo H in diabetic as opposed to nondiabetic subjects (NIDDM,
      29.9 +/- 10.8 mg/dL; IDDM, 31.3 +/- 9.9; controls, 22.5 +/- 7.7; F = 53.3, P =
      .0001). The relation between plasma lipids and apo H was simultaneously evaluated
      in the three groups with inclusion of diabetes, sex, body mass index (BMI), and
      age as covariates in the model. This analysis showed a strong positive
      correlation (P = .0009) between apo H and total cholesterol, and a weaker
      positive correlation with triglycerides ([TGs] P = .016). The correlation between
      apo H and hemoglobin A1c (HbA1c) levels in diabetics (P = .03) highlights the
      importance of glycemic control for plasma levels of this apoprotein, which is
      highly glycated. Although the role of apo H in lipid metabolism is still
      uncertain, recent investigations on the possible relation between plasma apo H
      levels and increased plasma lipids and thrombotic risk could explain the
      increased atherosclerotic risk in diabetic patients.

PMID- 9160819
TI  - Effects of acute hyperinsulinemia on testosterone serum concentrations in adult
      obese and normal-weight men.
AB  - In a previous study performed in adult obese and normal-weight male subjects, we
      found that suppression of insulin levels by diazoxide reduced testosterone and
      increased sex hormone-binding globulin (SHBG) blood concentrations. These and
      other data suggested that insulin may have a regulatory capacity in testosterone
      secretion and/or metabolism in men, similar to what has already been demonstrated
      in women. In this study, we investigated the effects of acute hyperinsulinemia on
      major androgen levels, including testosterone, in two groups of normal-weight in
      = 11) and obese (n = 9) men. Acute hyperinsulinemia was obtained by the
      euglycemic-hyperinsulinemic clamp technique. Relationships between the degree of
      insulin resistance (ie, total glucose disposal [M value]) and testosterone levels
      were also evaluated. Basal testosterone levels in obese subjects (10.40 +/- 3.02
      nmol/L) were significantly lower than in normal-weight controls (15.50 +/- 4.65
      nmol/L, P < .01), whereas no difference was present in androstenedione and
      dehydroepiandrosterone sulfate (DHEA-S) concentrations. During the clamp study,
      testosterone was significantly increased in the obese group (11.79 +/- 3.64
      nmol/L, P < .05) but not in the control group (15.81 +/- 4.54 nmol/L, P = NS).
      The other two androgens did not significantly change in either the obese or
      control group. There was a highly significant correlation between baseline
      testosterone concentrations, with M values suggesting a relationship between
      impaired peripheral insulin sensitivity and reduced plasma testosterone
      concentrations. It should be pointed out that there was a certain discrepancy in
      the testosterone variations, particularly in the control group, in which two
      thirds of the subjects had no change or some decrease in testosterone levels,
      whereas in the remainder testosterone increased over the values of the assay
      variation coefficient. These findings are consistent with the hypothesis that
      insulin may regulate testosterone blood levels also in male subjects. Whether
      these effects are primarily due to increased hormone secretion or reduced
      clearance needs to be investigated.

PMID- 9160820
TI  - Effect of a diet high in vegetables, fruit, and nuts on serum lipids.
AB  - We assessed the effect of a diet high in leafy and green vegetables, fruit, and
      nuts on serum lipid risk factors for cardiovascular disease. Ten healthy
      volunteers (seven men and three women aged 33 +/- 4 years [mean +/- SEM]; body
      mass index, 23 +/- 1 kg/m2) consumed their habitual diet (control diet, 29% +/-
      2% fat calories) and a diet consisting largely of leafy and other low-calorie
      vegetables, fruit, and nuts (vegetable diet, 25% +/- 3% fat calories) for two 2
      week periods in a randomized crossover design. After 2 weeks on the vegetable
      diet, lipid risk factors for cardiovascular disease were significantly reduced by
      comparison with the control diet (low-density lipoprotein [LDL] cholesterol, 33%
      +/- 4%, P < .001; ratio of total to high-density lipoprotein [HDL] cholesterol,
      21% +/- 4%, P < .001; apolipoprotein [apo] B:A-I, 23% +/- 2%, P < .001; and
      lipoprotein (a) [Lp(a)], 24% +/- 9%, P = .031). The reduction in apo B was
      related to increased intakes of soluble fiber (r = .84, P = .003) and vegetable
      protein (r = -.65, P = .041). On the vegetable compared with the control diet,
      the reduction in total serum cholesterol was 34% to 49% greater than would be
      predicted by differences in dietary fat and cholesterol. A diet consisting
      largely of low-calorie vegetables and fruit and nuts markedly reduced lipid risk
      factors for cardiovascular disease. Several aspects of such diets, which may have
      been consumed early in human evolution, have implications for cardiovascular
      disease prevention.

PMID- 9160821
TI  - Impact of long-term naltrexone treatment on growth hormone and insulin secretion
      in hyperandrogenic and normal obese patients.
AB  - The growth hormone (GH) response to stimulation tests is impaired in obesity.
      Moreover, obese patients exhibit a "paradoxical" increase of GH to GH-releasing
      hormone (GHRH) stimulation after food ingestion; this paradoxical response is
      reversed by naloxone infusion. On the other hand, beta-endorphin seems to exert
      profound effects on insulin release. Recent studies also demonstrated an
      impairment of GH response to several stimuli in polycystic ovary syndrome (PCOS),
      a condition associated with obesity, hyperinsulinism, and insulin resistance.
      Chronic inhibition of opioid tone by the opioid antagonist naltrexone (NTX) is
      able to reduce the insulin response to an oral glucose tolerance test (OGTT) in
      hyperinsulinemic PCOS patients. Since insulin and GH may reciprocally influence
      their secretion and the opioid system may have a role in the pathogenesis of
      hyperinsulinemia and reduced GH secretion, we have explored the involvement of
      these neuroendocrine mechanisms in essential obesity and in obesity associated
      with hyperandrogenism by a long-term treatment with an opiate antagonist. We
      tested seven obese patients affected by PCOS, seven matched women with essential
      obesity (EO), and five non-obese control subjects. All patients, in the
      follicular phase, underwent an OGTT (75 g) and basal hormone assay. Two days
      later, patients were subjected to a GHRH test. The patients then had 4 weeks of
      treatment with NTX 50 mg/d. Following continuation of the treatment, OGTT and
      GHRH tests were repeated. Insulin-like growth factor-I (IGF-I) and IGF-binding
      protein-3 (IGFBP-3) plasma concentrations were also determined in the basal
      condition before and after NTX treatment. NTX treatment reduced fasting insulin
      levels in patients with EO (P < .05) and restored a normal GH response to GHRH
      without affecting IGF-1 and IGFBP-3 levels. In PCOS subjects, NTX reduced the
      insulin response to a glucose load and failed to modify the blunted GH response
      to GHRH. Our data suggest a significant difference in opioid system function in
      PCOS and EO subjects, indicating a particular form of obesity in PCOS. The opiate
      antagonist treatment in EO may act through the reduction of negative insulin
      feedback on GH secretion. In PCOS patients, the failure to improve GH secretion
      in obese hyperandrogenized patients may be related to a high opioidergic tone or
      to the inhibitory predominance of other neurotransmitters.

PMID- 9160822
TI  - Effect of ethanol and fructose on plasma uridine and purine bases.
AB  - To determine whether both ethanol and fructose increase the plasma concentration
      of uridine, we administered ethanol (0.6 g/kg) or fructose (1.0 g/kg) to seven
      normal subjects. Both ethanol and fructose increased the plasma concentration of
      uridine together with an increase in the plasma concentration of oxypurines,
      whereas fructose also increased the plasma concentration of uric acid, but
      ethanol did not. In ethanol ingestion and fructose infusion, an increase in the
      plasma concentration of purine bases correlated with that of uridine. These
      results strongly suggest that an increase in the plasma concentration of uridine
      is ascribable to increased pyrimidine degradation following purine degradation
      increased by ethanol and fructose.

PMID- 9160823
TI  - Activation of mitogen-activated protein kinase in freshly isolated rat
      hepatocytes by both a calcium- and a protein kinase C-dependent pathway.
AB  - In the present study, we investigated the role of calcium and protein kinase C
      (PKC) in the activation of mitogen-activated protein kinase (MAPK) in isolated
      rat hepatocytes. We found that the glycogenolytic hormone norepinephrine (NE),
      acting through the alpha1-adrenergic receptor and the G protein Gq, was able to
      induce a dose- and time-dependent activation of MAPK in hepatocytes. Vasopressin,
      which acts through a different receptor but also through stimulation of the Gq
      dependent pathway, also caused a twofold activation of MAPK. Activation of MAPK
      by both agonists required the presence of free extracellular calcium and was
      blocked by the specific PKC inhibitor, Ro 31-8220. MAPK activation was also
      induced by phorbol myristate acetate (PMA), confirming that a PKC-dependent
      pathway exists for MAPK activation in liver. Furthermore, calcium-mobilizing
      agents such as thapsigargin and ionomycin were able to induce an activation of
      MAPK by a PKC-independent pathway that was totally abolished by preincubation of
      cells with EGTA. A second pathway for MAPK activation that relies solely on
      calcium may therefore exist. Ro 31-8220 did not affect phosphorylase activation
      by NE, vasopressin, thapsigargin, and ionomycin, indicating that PKC inhibition
      did not interfere with the signaling pathway leading to inositol-1,4,5
      triphosphate (IP3)-induced calcium mobilization or with changes in calcium
      fluxes. The role of MAPK activation by NE and vasopressin in the regulation of
      hepatic carbohydrate metabolism is discussed.

PMID- 9160824
TI  - Increases in high-density lipoprotein cholesterol with endurance exercise
      training are blunted in obese compared with lean men.
AB  - The effectiveness of endurance exercise training (without concomitant weight
      loss) for improving lipoprotein lipid levels in obese individuals remains
      controversial. The purpose of this study was to determine whether lipoprotein
      lipid responses to endurance exercise training are affected by obesity. Healthy
      middle-aged and older (57 +/- 2 years) lean (n = 16; body mass index [BMI], 22 to
      26 kg/m2), moderately obese (n = 15; BMI, 27 to 30 kg/m2), and obese (n = 15;
      BMI, 31 to 37 kg/m2) men underwent a 9-month endurance exercise training program.
      The groups differed in the initial degree of obesity, waist circumference, and
      waist to hip ratio (WHR), but not in age or maximal aerobic capacity ( VO2max).
      The obese group had lower baseline levels of high-density lipoprotein cholesterol
      (HDL-C) and HDL2-C, and higher triglyceride (TG) levels than the lean group.
      Exercise training increased VO2max to a comparable degree in lean, moderately
      obese, and obese groups (18%, 24%, and 18%, respectively, P < .01). Exercise
      training significantly decreased TG levels in all groups, whereas total
      cholesterol and low-density lipoprotein cholesterol (LDL-C) decreased only in the
      obese group. Exercise training increased HDL-C and HDL2-C levels in lean (14% and
      81%, respectively, P < .05) and moderately obese (7% and 59%, respectively, P <
      .05) men, whereas neither HDL-C nor HDL2-C changed in obese men. The change in
      HDL-C correlated negatively with initial BMI (r = -.42, P < .01) and waist
      circumference (r = -.43, P < .01). These results show that the effects of
      exercise training on HDL-C are blunted in obese middle-aged and older men,
      whereas improvements in TG occur independently of the degree of obesity.

PMID- 9160825
TI  - Differential acute effects of oxovanadiums and insulin on glucose and lactate
      metabolism under in vivo and in vitro conditions.
AB  - Oxovanadium compounds such as vanadate and peroxovanadiums have been shown to
      have insulin-mimetic effects on various metabolic pathways, including glucose
      metabolism. A differential effect of various oxovanadium species on glucose
      metabolism in different tissues has been reported. The results from our present
      in vivo studies using rats show that peroxovanadiums and insulin have similar
      acute effects on decreasing blood glucose levels, but dissimilar effects on blood
      lactate levels. Furthermore, when bisperoxovanadate (BPV) was administered
      acutely to intact animals immediately before a bolus insulin challenge, it
      blunted the effectiveness of insulin in decreasing the blood lactate level, but
      at the same time demonstrated a synergistic effect on the hypoglycemic action of
      insulin. It was also observed in in vitro studies using normal 3T3-L1 adipocytes
      (not serum-deprived) that 1,10-phenanthroline bisperoxovanadate (PHEN-BPV)
      attenuates the incorporation of carbon from lactate but not from glucose, into
      lipid in both the absence and presence of insulin. Additionally, it was observed
      that PHEN-BPV had no effect on lactate dehydrogenase (LDH) activity. Thus, one
      may speculate that PHEN-BPV interferes with carrier-mediated lactate transport.
      These observations demonstrate that insulin and oxovanadiums differ in the
      handling of different metabolic substrates. Thus, even though oxovanadiums mimic
      many of the metabolic actions of insulin, their metabolic effects are by no means
      identical. Moreover, since vanadate had no acute effect on glucose metabolism
      under in vivo conditions, this may suggest that to be effective as a hypoglycemic
      agent vanadate needs to be converted to some other biologically active
      oxovanadium species. Finally, the observed interference by PHEN-BPV in the
      metabolism of lactate may predispose subjects using oral vanadate, as a part of
      the therapeutic regimen for management of diabetic hyperglycemia, to lactic
      acidosis.

PMID- 9160826
TI  - Urea and protein metabolism in burned children: effect of dietary protein intake.
AB  - The response of urea metabolic kinetics, the rate of whole-body protein
      breakdown, and muscle and skin protein synthesis rates to dietary protein intake
      (1.15 to 2.92 g/kg/d) was assessed in children with 20% to 40% total body surface
      area burn injury using a primed continuous infusion of 15N2-urea and L-13C6
      phenylalanine. Plasma urea concentration, production, and excretion rates
      increased with dietary protein intake without evidence of approaching maximum
      plateau values. There was no consistent evidence of urea recycling in these
      subjects (urea production = excretion) at any level of protein intake. The rate
      of appearance (Ra) of phenylalanine (an index of whole-body protein breakdown)
      and rate of muscle protein synthesis were independent of dietary protein, whereas
      there was a significant increase in skin protein synthesis with higher protein
      intake. We conclude that there seems to be little benefit of high protein intake
      on whole-body protein breakdown and muscle protein synthesis rates in these burn
      patients, although high-protein diets may enhance wound healing.

PMID- 9160827
TI  - Tumor necrosis factor inhibits the transcriptional rate of glucose-6-phosphatase
      in vivo and in vitro.
AB  - Recombinant human tumor necrosis factor-alpha (TNF) injection in mice was
      associated with a reduced blood glucose level, already manifest 6 hours following
      cytokine administration. Insulin levels were not affected. Glycogen content was
      decreased in a dose-dependent and time-response manner. The activity of glucose-6
      phosphatase (G6Pase) was already reduced 6 hours after TNF injection and was
      sustained 12 hours afterward. Phosphoenolpyruvate carboxykinase (PEPCK) activity
      was not affected initially (6 hours after injection), but a 50% reduction was
      observed 12 hours following cytokine administration compared with levels in
      fasting controls. Both liver G6Pase and PEPCK mRNAs were markedly reduced due to
      an inhibition of the transcriptional rate. A direct inhibitory effect of TNF on
      G6Pase promoter activity was demonstrated using HuH-7 cells transiently
      transfected with G6Pase promoter, fused to a reporter gene.

PMID- 9160828
TI  - Kinetics of retinyl esters during postprandial lipemia in man: a compartmental
      model.
AB  - Orally ingested vitamin A (retinol) is incorporated into intestinal chylomicrons
      (CHYLO) in the form of retinyl esters (RE) along with newly absorbed dietary
      triglycerides (TG). As the intestinal lipoproteins undergo hydrolysis in the
      circulation, the majority of the RE remain with the secreted intestinal particles
      and have been used as a marker for intestinally derived lipoproteins during the
      early phase of the postprandial state. A multicompartmental model was developed
      for the kinetics of RE during postprandial lipemia in individuals with normal
      lipid levels (n = 16) and in patients with hyperlipidemia (n = 44). The
      assumptions used in the development of the model are presented in this report.
      Some of the key findings include (1) as much as 50% of the newly synthesized RE
      may be secreted by the intestine as very-low-density lipoprotein (VLDL)-sized
      particles of S(f) 20 to 400 following consumption of a test meal containing a
      moderate amount of fat (20 to 30 g); (2) in most individuals, approximately 50%
      of the RE secreted in S(f) greater than 400 are converted to smaller, less
      buoyant fractions, and 50% are irreversibly removed directly from the plasma; (3)
      as much as 5% to 20% of the ingested retinol may be secreted as small intestinal
      lipoproteins with the buoyance of low-density lipoprotein (LDL) in some
      individuals; and (4) less than 5% of RE flux through S(f) 20 to 400 is converted
      to S(f) less than 20, and the primary catabolic pathway for RE in this fraction
      is direct uptake. Comparable estimates can be obtained for the kinetic parameters
      when repeat studies are made in the same subjects under comparable conditions.

PMID- 9160829
TI  - Myosin light chain kinase in endothelium: molecular cloning and regulation.
AB  - The phosphorylation of myosin light chains by myosin light chain kinase (MLCK) is
      a key event in agonist-mediated endothelial cell gap formation and vascular
      permeability. We now report the cloning and expression of a nonmuscle MLCK
      isoform in cultured endothelium. Screening of a human endothelial cell cDNA
      library identified a 7.7 kb cDNA with substantial (> 95%) homology to the coding
      region of the rabbit and bovine smooth muscle (SM) MLCK (amino acid #923-1913) as
      well as with the reported avian nonmuscle MLCK (65-70% homology). Sequence
      analysis also identified, however, a 5' stretch of novel sequence (amino acids #1
      922) which is not contained in the open reading frame of mammalian SM MLCK, and
      is only 58% homologous to the avian fibroblast MLCK sequence. Immunoprecipitation
      with NH2-specific antisera revealed a 214 kD high molecular weight MLCK in bovine
      and human endothelium which exhibits MLC phosphorylation properties. Amino acid
      sequence analysis revealed endothelial MLCK consensus sequences for a variety of
      protein kinases including highly conserved potential phosphorylation sites for
      cAMP-dependent protein kinase A (PKA) in the CaM-binding region. Augmentation of
      intracellular cAMP levels markedly enhanced MLCK phosphorylation (2.5-fold
      increase) and reduced kinase activity in MLCK immunoprecipitates (4-fold
      decrease). These data suggest potentially novel mechanisms of endothelial cell
      contraction and barrier regulation.

PMID- 9160830
TI  - The role of nitric oxide in limiting gene transfer: parallels to viral host
      defenses.

PMID- 9160831
TI  - Asthma: does IL-5 have a more provocative role?

PMID- 9160833
TI  - Cytokine and eosinophil responses in the lung, peripheral blood, and bone marrow
      compartments in a murine model of allergen-induced airways inflammation.
AB  - Selective accumulation of eosinophils and activated CD4+ cells is now considered
      a central event in the pathogenesis of asthma, and this process is thought to be
      mediated by a number of cytokines including tumor necrosis factor-alpha (TNF
      alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), and the Type 2
      cytokines interleukin-4 (IL-4) and IL-5. To carry out a detailed time-course
      analysis of cellular changes in the bronchoalveolar lavage fluid (BAL),
      peripheral blood (PB), and bone marrow (BM), and of changes in the aforementioned
      cytokines in BAL and serum, Balb/c mice were sensitized by intraperitoneal
      injection with ovalbumin (OVA) adsorbed to aluminum hydroxide on two occasions 5
      days apart, and were subjected to an OVA aerosol challenge 12 days after the
      second sensitization. This resulted in an airways inflammatory response
      characterized by early transient neutrophilia, marked eosinophilia, and, to a
      lesser extent, lymphocytosis in the BAL. Inflammatory events were first observed
      3 h and 24 h after antigen challenge in the lung tissue and BAL, respectively,
      and lasted for 21 days. In the BM, we detected a 1.5- and 5-fold increase in the
      total number of cells and eosinophils, respectively, 4 days after the second
      sensitization. This was followed by a decrease, although BM eosinophilia remained
      clearly present at the time of antigen challenge. A second eosinopoietic event
      was observed in the BM shortly after challenge and reached a peak at day 3. BM
      cellularity returned to normal at day 21 after challenge. Serum OVA-specific IgE
      was first detected 3 days following the second sensitization (150 ng/ml). IgE
      levels then decreased but remained at the 75 ng/ml range at the time of the
      aerosol challenge. During the sensitization period, TNF-alpha (approximately 25
      pg/ml), IL-4 (approximately 40 pg/ml), and IL-5 (approximately 250 pg/ml) were
      detected in serum, but not in the BAL fluid (BALF) and returned to background
      levels at the time of the antigen challenge. After antigen challenge, TNF-alpha,
      IL-4, IL-5, and GM-CSF were detected in serum. Peak levels were observed at 3 h
      (approximately 40 pg/ml), 3 h (approximately 120 pg/ml), 12 h (approximately 350
      pg/ml), and 3 h (approximately 10 pg/ml), respectively, and returned to
      background levels 24 h after challenge. In the BALF, we detected peak levels of
      TNF-alpha, IL-4, IL-5, and GM-CSF at 6 h (approximately 250 pg/ml), 24 h
      (approximately 140 pg/ml), 24 h (350 pg/ml), and 3 h (approximately 10 pg/ml),
      respectively, with a return to background levels 5 days after challenge. No IL-10
      could be detected at any time point during sensitization or after challenge in
      either serum or BAL. We also detected approximately 40 pg/ml of interferon-gamma
      (IFN-gamma) in the serum of normal untreated mice. Serum IFN-gamma levels
      fluctuated during sensitization and after challenge, but never exceeded those
      observed in untreated mice. Thus, the cytokine profile observed in this
      experimental model of allergic inflammation is characterized by IL-4 and IL-5
      dominance, with an apparently minor TNF-alpha and GM-CSF contribution and
      relatively low or undetectable levels of IFN-gamma and IL-10.

PMID- 9160832
TI  - Modulation of adenovirus-mediated gene transfer by nitric oxide.
AB  - We assessed the role of .NO in recombinant adenovirus-mediated gene transfer both
      in vitro and in vivo. NIH3T3 fibroblasts, stably transfected with the human
      inducible nitric oxide synthase, but lacking tetrahydrobiopterin (NIH3T3/iNOS
      [inducibile nitric oxide synthase]), were infected with replication-deficient
      adenovirus (E1-deleted), containing either the luciferase or the Lac Z reporter
      genes (AdCMV-Luc and AdCMV-Lac Z; 1-10 plaque forming units [pfu]/cell).
      Incubation of infected cells with sepiapterin (50 microM), a precursor of
      tetrahydrobiopterin, progressively increased nitrate/nitrite levels in the medium
      and decreased both luciferase and beta-galactosidase protein expression to
      approximately 60% of their corresponding control values, 24 h later. NIH3T3/iNOS
      cells had normal ATP (adenosine 5'-triphosphate) levels and did not release
      LDH(lactic dehydrogenase) into the medium. Pretreatment of these cells with N(G)
      monomethyl-L-arginine (L-NMMA; 1 mM), an inhibitor of iNOS, prevented the
      sepiapterin-mediated induction of .NO and restored gene transfer to baseline
      values. Incubation of NIH3T3/iNOS with 8-bromo-cGMP (400 microM) in the absence
      of sepiapterin, or exposure of AdCMV-Luc to large concentrations of .NO, did not
      alter the efficacy of gene transfer. .NO produced by NIH3T3/iNOS cells also
      suppressed beta-galactosidase expression in NIH3T3 cocultured cells stably
      transfected with beta-galactosidase gene, suggesting .NO inhibited gene
      expression at either the transriptional or posttranscriptional levels. To
      investigate the effects of inhaled .NO on gene transfer in vivo, CD1 mice
      received an intratracheal instillation of AdCMV-Luc (4 x 10(9) pfu in 80 microl
      of saline) and exposed to .NO (25 ppm in room air) for 72 h. At that time, no
      significant degree of lung inflammation was detected by histological examination.
      However, lung luciferase activity decreased by 53% as compared with air breathing
      controls (P < 0.05; n > or = 8). We concluded that overproduction of .NO
      decreases the efficiency of adenovirus-mediated gene transfer in lung cells in
      the absence of cytotoxicity or inflammation.

PMID- 9160834
TI  - Mucous cell metaplasia in rat nasal epithelium after a 20-month exposure to
      ozone: a morphometric study of epithelial differentiation.
AB  - The present study was designed to examine the effects of long-term ozone exposure
      on nasal epithelia and intraepithelial mucosubstances (IM) throughout the nasal
      airways of F344/N rats. Animals were exposed to 0 (controls), 0.12, 0.5, or 1.0
      ppm ozone, 6 h/day, 5 days/wk, for 20 mo. Rats were killed 1 wk after the end of
      the exposure, and nasal tissues were processed for light and electron microscopy.
      Standard morphometric techniques were used to determine epithelial cell densities
      and the amounts of IM in the surface epithelium lining the nasal airways. No
      mucous cells or IM were present in the epithelia lining the nasal lateral meatus
      and maxillary sinus of rats exposed to 0 or 0.12 ppm ozone. In contrast, rats
      exposed to 0.5 or 1.0 ppm ozone had marked mucous cell metaplasia (MCM) with
      numerous mucous cells and conspicuous amounts of IM in the surface epithelium
      lining these upper airways. Ozone-induced increases in total epithelial cells
      (i.e., epithelial hyperplasia) were present only in rats exposed to 1.0 ppm. The
      results of this study indicate that rats chronically exposed to 1.0 or 0.5 ppm,
      but not 0.12 ppm, ozone can develop marked MCM with significant increases in IM
      in both proximal and distal nasal airways. The epithelial changes observed
      throughout the nasal passages of ozone-exposed rats may be adaptive responses in
      an attempt to protect the upper and lower respiratory tract from further ozone
      induced injury.

PMID- 9160835
TI  - Adenosine A3 receptor expression and function in eosinophils.
AB  - The A3 adenosine receptor is widely expressed in human tissues with the most
      abundant expression in the lung and liver, but the predominant cellular
      localization and functions of this receptor in humans are unknown. Since
      adenosine influences the activation of circulating and resident inflammatory
      cells within the lung and leads to exaggerated airway narrowing in individuals
      with inflammatory airway disorders, we hypothesized that A3 receptor gene
      expression is localized to inflammatory cells and that gene expression is
      upregulated in airway inflammation. Lung and airway tissue were obtained at
      thoracotomy from nonsmoking subjects and subjects with inflammatory airway
      disorders associated with tobacco smoke or asthma. In situ hybridization
      identified A3 receptors in mesenchymal cells and eosinophils within the lamina
      propria of the airways and the adventitia of blood vessels, but not in mast
      cells. A3 receptor transcripts were highly expressed in peripheral blood
      eosinophils purified from atopic donors (6.36 +/- 0.60 pg/microg total RNA) in
      comparison with neutrophils (0.26 +/- 0.06 pg/microg) or mononuclear cells (0.9
      +/- 0.15 pg/microg). Mean A3 receptor transcript abundance was greater in lung
      tissue from subjects with airway inflammation (0.33 +/- 0.04 pg/microg total RNA)
      than in normal lung (0.24 +/- 0.03 pg/microg total RNA, P = 0.035). The A3
      receptor agonist N6-(4-amino-3-iodobenzyl)adenosine dose-dependently inhibited
      platelet activating factor-induced eosinophil chemotaxis to a maximum of 41%.
      This inhibitory effect was completely abolished by addition of the A3 receptor
      selective antagonist 3-(3-iodo-4-aminobenzyl)-8-(4-oxyacetate)phenyl-1
      propylxanthine. We conclude that A3 receptors are primarily expressed on
      eosinophils in human lung, where they mediate inhibition of eosinophil
      chemotaxis. Specific A3 receptor ligands may be useful agents in the treatment of
      eosinophil-dependent diseases such as asthma and rhinitis.

PMID- 9160836
TI  - Re-emergence of a fetal pattern of insulin-like growth factor expression during
      hyperoxic rat lung injury.
AB  - Chronic injury to the developing lung results in cell proliferation and
      characteristic architectural changes. It is likely that growth factors produced
      and acting locally are important to these processes. Insulin-like growth factors
      I and II (IGF-I and IGF-II) are peptide growth factors expressed by lung cells.
      Roles for IGF-I and IGF-II in lung injury are suggested by their expression
      during lung development and by studies showing changes in IGF-I expression by
      activated alveolar macrophages, and increases in IGF-II peptide in oxidant
      arrested alveolar epithelial cells. To investigate whether the expression of IGF
      I and IGF-II are changed with hyperoxic exposure, newborn rats were exposed to 80
      90% oxygen for up to 6 wk and Northern hybridization analyses, in situ
      hybridization histochemistry, immunohistochemical staining, and reverse
      transcription-polymerase chain reaction (RT-PCR) studies were performed. Northern
      hybridization analyses of RNA extracted from whole lung showed increases in IGF-I
      and IGF-II mRNAs with prolonged hyperoxia. In situ hybridization histochemistry
      and immunohistochemical staining demonstrated spatial patterns of IGF-I and IGF
      II expression similar to those seen during fetal lung development. In addition,
      alveolar macrophages express IGF-I and type II epithelial cells express IGF-II in
      control and oxygen-injured lung. These results suggest that in lung injury
      resident lung cells may re-express IGFs in a manner reminiscent of fetal
      development, and activated inflammatory cells may contribute to the proliferative
      response through autocrine and paracrine mechanisms.

PMID- 9160837
TI  - Enhanced expression of neutral endopeptidase (NEP) in airway epithelium in
      biopsies from steroid- versus nonsteroid-treated patients with atopic asthma.
AB  - The expression of the endogenous neuropeptide-degrading enzyme, neutral
      endopeptidase (NEP; CALLA, CD10, E.C.3.4.24.11) on cultured human airway
      epithelial cells can be upregulated by corticosteroids. We examined whether NEP
      expression in the airway epithelium or lamina propria in bronchial biopsies is
      enhanced in atopic asthmatics on regular inhaled steroids as compared with those
      without steroid treatment. Forty nonsmoking adults (age 19 to 48 yr) with mild to
      moderate asthma (forced expiratory volume in 1 s > or = 50% pred., histamine PC20
      range 0.02 to 7.6 mg/ml) with (n = 23) or without (n = 17) regular inhaled
      steroids treatment entered the study. Biopsies were taken at (sub)segmental level
      from the right lower lobe, the middle lobe, and the main carina.
      Immunohistochemical staining was performed on cryostat sections using the VIL-A1
      monoclonal antibody against CD10 (NEP). Intra- and inter-observer repeatability
      of a semiquantitative scoring method was good as assessed by weighted kappa
      (kappa(w) ranging from 0.66 to 0.81). In the airway epithelium, NEP-positive
      sites were within the basal layer and, in contrast with studies applying other
      antibodies, also at apical sites and within the lamina propria. In both the
      epithelium and lamina propria, NEP expression was not significantly different
      between the three biopsy sites (Friedman's nonparametric two-way analysis of
      variance; P > 0.68), nor was expression in the lamina propria associated with
      inhaled steroid usage (Mann-Whitney U test; P = 0.98). However, NEP expression
      was significantly enhanced in the airway epithelium in patients using inhaled
      steroids as compared with nonsteroid users (mean rank: 23.4 and 15.5,
      respectively; P = 0.02). Among nonsteroid-using subjects, NEP expression was
      related to symptoms and the methacholine PC20 (Rs: -0.69 and 0.49, respectively;
      P < or = 0.04). We conclude that the expression of NEP is enhanced in airway
      epithelium in bronchial biopsy specimens from patients with atopic asthma who are
      regularly using inhaled steroids as compared with patients who do not. This fits
      the hypothesis that the anti-inflammatory effect of corticosteroids within the
      airways is partially mediated by the upregulation of the endogenous neuropeptide
      degrading enzyme NEP.

PMID- 9160838
TI  - Hyperoxic injury decreases alveolar epithelial cell expression of vascular
      endothelial growth factor (VEGF) in neonatal rabbit lung.
AB  - Normal neonatal lung growth requires a substantial increase in microvascular
      endothelial cells. Oxygen injury to neonatal lung destroys endothelial cells and
      alters the normal process of alveolarization, including development of the
      microvasculature. The mechanisms that regulate lung alveolar capillary growth and
      development are not known. Vascular endothelial growth factor (VEGF) is a
      specific mitogen for endothelial cells that is often expressed by epithelial
      cells in close proximity to capillary beds. VEGF expression is induced by hypoxia
      and may be inhibited by hyperoxia. We examined the cell-specific expression of
      VEGF during normal postnatal lung development and the effects of hyperoxic lung
      injury on VEGF mRNA and protein in vivo. Normal newborn rabbits between 1 day and
      5 wk of age had VEGF transcripts located mainly in alveolar epithelial cells,
      with little or no VEGF mRNA noted in smooth muscle or endothelial cells. A
      subpopulation of freshly isolated, normal type II cells, but not mesenchymal
      cells, expressed VEGF mRNA. Newborn rabbits exposed to 100% oxygen for 4 days had
      no change in VEGF mRNA abundance, transcript location, or immunostaining. Animals
      exposed to 100% oxygen for an average of 9 days had an 80% decrease in lung VEGF
      mRNA abundance, decreased alveolar epithelial cell VEGF expression, and decreased
      VEGF immunostaining. Recovery of VEGF expression to control levels occurred
      during a 5-day recovery period. We conclude that alveolar epithelial cells in
      postnatal lung express VEGF, suggesting epithelial regulation of alveolar
      capillary formation. Furthermore, hyperoxic injury decreases neonatal lung VEGF
      mRNA and protein, which may be a contributory mechanism of impaired postnatal
      microvascular development in oxygen injury.

PMID- 9160839
TI  - Early fetal development of lung vasculature.
AB  - Despite its relevance to a variety of congenital anomalies, the earliest stages
      of lung vascular development are poorly understood. In other organs, two
      processes have been identified: vasculogenesis, the development of blood lakes in
      mesenchyme, and angiogenesis, the branching of new vessels from preexisting ones.
      In the present study we established the events in the development of the lung's
      vasculature in Swiss-Weber mouse fetuses between 9 and 20 days gestation, using
      light microscopy (LM), transmission electron microscopy (TEM), barium-gelatin
      angiograms, and scanning electron microscopy (SEM) of Mercox (methyl
      methacrylate) vascular casts. Three features were identified: (1) central
      sprouting or angiogenesis for up to approximately seven generations (counting the
      artery to each lung as first generation); (2) the formation of peripheral lakes
      by vasculogenesis; and (3) the development of communications between the central
      and peripheral systems. At 9 days gestation, intercellular spaces were apparent
      in the lung mesenchyme; these were formed by discharge of vesicles from
      mesenchymal cells, which then regrouped to provide "endothelial" cells lining the
      spaces. The isolated lakes coalesced to form sinusoidal spaces of irregular
      profile. At 12 days gestation, the earliest time at which were able to make a
      cast, sprouting of arteries and veins from the central pulmonary vascular trunks
      was apparent. Between 13 and 14 days gestation the earliest connection between
      the peripheral and central spaces was identified. Such connections became more
      numerous and dense by term. Similar images seen on examination of human fetal
      lung sections by LM indicated that similar processes occur in the vascular
      development of the human lung.

PMID- 9160840
TI  - Functional, morphological, and phenotypical differences between rat alveolar and
      interstitial macrophages.
AB  - Alveolar macrophages (AM) and interstitial macrophages (IM) from rat lungs were
      characterized with respect to morphology, phagocytosis, adhesion properties, and
      phenotype. AM were recovered by lung lavage and IM by treatment of the lung
      tissue with DNAse and collagenase. The AM were enzyme treated in the same way as
      the IM. The IM were smaller than AM and had a higher nuclear to cytoplasm ratio.
      They had markedly lower phagocytic capacity. The attachment of particles to the
      cell surface was significantly lower in IM than in AM, but the capacity to ingest
      the particles was the same. Adherence to vitronectin- as well as fibronectin
      coated surfaces was significantly higher in AM. The phagolysosomal pH was similar
      in IM and AM, around pH 5, indicating that dissolution of inorganic particles can
      take place effectively also in IM. Five surface receptors were studied, and the
      expression differed significantly in all five between AM and IM. The expression
      of OX-1 (CD 45), a common leukocyte antigen, was significantly higher on AM as
      was the expression of CD 71 (transferrin receptor). The receptor density for OX
      42 was higher on a fraction of IM. This might be compatible with a stronger
      interaction between these cells and, for example, matrix components. IM had more
      surface antigen expressing MHC class Ia (OX-6) and CD 54. Both receptors are
      important for the antigen presentation capacity of macrophages. These findings
      show profound differences in phenotype between AM and IM and indicate that IM is
      a highly immunocompetent cell and should not be regarded only as a precursor to
      AM.

PMID- 9160841
TI  - Inhibition of ERK activation attenuates endothelin-stimulated airway smooth
      muscle cell proliferation.
AB  - Endothelin is a small peptide that is a potent bronchoconstrictor, mitogen for
      airway smooth muscle (ASM), and is believed to be involved in the pathogenesis of
      asthma. To understand how endothelin stimulates the proliferation of ASM cells in
      culture, we evaluated the relationship between mitogen activated protein (MAP)
      kinase activation and cell proliferation. Endothelin is a potent stimulator of
      the extracellular regulated kinase 2 (ERK2) subgroup of MAP kinases, and ERK2
      activation was tightly correlated with the proliferation of rat ASM cells.
      PD98059, a small molecule inhibitor of MEK (MAP or ERK kinase) was used to
      establish the role of ERK2 activation in the endothelin-stimulated signal
      transduction pathway leading to cell proliferation. While PD98059 significantly
      inhibited the ability of endothelin to activate ERK, the drug did not appear to
      effect the catalytic activity of an activated MEK mutant, or ERK in vitro. The
      data suggest that the mechanism of PD98059 inhibition of the ERK2 pathway in ASM
      cells may involve inhibition of MEK activation. The endothelin signal
      transduction pathway that culminates in ERK2 activation was dependent on protein
      kinase C (PKC), since depletion of PKC significantly inhibited the ability of
      endothelin to activate ERK2. Taken together, the data imply that activation of
      ERK is a critical endpoint in the endothelin signal transduction pathway since
      inhibition of this kinase inhibits endothelin-induced ASM cell proliferation.

PMID- 9160842
TI  - Production of cytokeratin 19 fragment by human squamous lung cancer cell lines.
AB  - Cytokeratins form part of the cytoskeleton of both normal and malignant
      epithelium. A novel tumor marker measuring cytokeratin 19 (CK-19) fragment has
      been introduced and proven to be suitable for monitoring therapy and following
      cases of non-small cell lung cancer, squamous cell lung cancer in particular.
      However, whether the serum level of CK-19 fragment reflects the number of
      proliferating tumor mass remains unknown. We studied the CK-19 fragment produced
      by two human squamous cell lung cancer cell lines. In Western blotting analysis,
      culture supernatants of both cell lines displayed bands of 37 and 40 kDa, which
      represented the CK-19 fragment and the intact CK-19, respectively. Gel filtration
      demonstrated that a part of soluble CK-19 was released as a large complex form in
      culture supernatants. The level of CK-19 fragment in culture supernatants
      increased during the exponential growth phase. CK-19 level decreased by an
      addition of a cytotoxic agent to non-significant level though the transient
      release of CK-19 fragment occurred during the first 2 days. After all, soluble CK
      19 fragments were detected in culture supernatants of human lung cancer cell
      lines and its level reflected proliferating cancer cells though it was not
      determined whether CK-19 fragments were released directly from live cells.

PMID- 9160843
TI  - Sphingomyelin metabolism is developmentally regulated in rat lung.
AB  - We investigated several indices involved in sphingomyelin metabolism in
      developing rat lung. The levels of sphingomyelin gradually increased during lung
      maturation, with highest levels observed postnatally. The content of sphingosine
      and ceramide, biologically active sphingomyelin degradation products, did not
      significantly change in microsomes during the prenatal period, but increased to
      peak levels in neonatal and adult lung, respectively. Sphingosine content
      increased 6-fold between the fetal (Day 21) and neonatal period. The
      developmental profiles of two enzymes involved in sphingomyelin synthesis, serine
      palmitoyltransferase and sphingomyelin synthase, were similar. Serine
      palmitoyltransferase activity increased progressively from the fetal to neonatal
      period, and plateaued at high levels in the adult lung. The activity of serine
      palmitoyltransferase correlated with the levels of endogenous sphingolipid in
      lung tissue. Sphingomyelin synthase activity also increased during fetal lung
      development, but attained highest levels at Day 21 gestation; postnatally, enzyme
      activity was detected at lower levels. The activities of the sphingolipid
      hydrolases, acid and neutral sphingomyelinase and acid and alkaline ceramidase,
      were elevated in fetal lung, thereafter declining to low levels after birth.
      Studies conducted in alveolar macrophages, fibroblasts, and alveolar type II
      epithelial cells revealed that these developmental changes in enzyme activities
      in lung tissue were also occuring globally at the cellular level and were not
      restricted to any specific cell population. These studies suggest that the
      developmental increase in lung sphingomyelin content is due to coordinate
      regulation of enzymes involved in the biosynthesis and degradation of
      sphingomyelin. These observations also suggest a regulatory role for serine
      palmitoyltransferase in the generation of long chain sphingoid bases.

PMID- 9160844
TI  - Protein tyrosine phosphatases mediate cell readhesion in alveolar epithelial
      cells mechanically separated from in vitro matrix.
AB  - Alveolar epithelial type II cells are the progenitor cells for restoring the
      alveolar epithelial barrier after acute lung injury. During repair of lung
      injury, the alveolar epithelial type II cells reepithelialize denuded air spaces,
      a process that involves breaking and reforming cell adhesions. A novel technique
      of mechanical separation of cultured alveolar epithelial cells from in vitro
      matrix was used to examine the intracellular signals that result when alveolar
      epithelial cell adhesions are broken. The results show that the tyrosine
      phosphorylation levels of focal adhesion kinase, paxillin, and pp60(src)
      decreased immediately after mechanical separation of the cells. Levels returned
      to nearly normal by 24 h after mechanical separation. Paxillin and pp60(scr)
      coprecipitated with focal adhesion kinase regardless of their phosphorylation
      state. Interestingly, the tyrosine phosphorylation level of the mitogen-activated
      protein kinase, p42(erk2), increased 15 min after mechanical separation.
      Preincubation of cell monolayers with phenylarsine oxide, a protein tyrosine
      phosphatase inhibitor, blocked the decrease in tyrosine phosphorylation levels of
      focal adhesion kinase, paxillin and pp60(src). Phenylarsine oxide incubation also
      prevented readhesion of mechanically separated cells at 24 h, but genistein, a
      tyrosine kinase inhibitor, had no effect. We conclude that protein tyrosine
      phosphatases are activated immediately after cultured alveolar epithelial cells
      are mechanically separated from in vitro matrix, and their activation is required
      for alveolar epithelial cell readhesion.

PMID- 9160845
TI  - Additive deficits in the choice accuracy of rats in the delayed non-matching to
      position task after cholinolytics and serotonergic lesions are non-mnemonic in
      nature.
AB  - The role of serotonin (5-HT) and its interaction with the muscarinic or nicotinic
      receptor-mediated mechanisms in the modulation of working memory and motor
      activity was investigated by assessing the effects of 5-HT lesion and cholinergic
      receptor blockade on the performance of rats in a working memory (delayed non
      matching to position, DNMTP) task. A global serotonergic lesion was induced by
      the intracerebroventricular administration of 5,7-dihydroxytryptamine (5,7-DHT).
      Post-mortem neurochemical analysis revealed that serotonin and 5
      hydroxyindoleacetic acid (5-HIAA) levels were reduced in frontal and parieto
      occipital cortices and in hippocampi of 5,7-DHT lesioned rats. 5-HIAA levels were
      also reduced in striatum. 5,7-DHT lesion slightly impaired choice accuracy of
      rats in the DNMTP task and also transiently reduced motor activity in rats. Even
      the lower dose of scopolamine (0.075 mg/kg), a muscarinic receptor antagonist,
      impaired the choice accuracy already at the shortest delay (i.e. not indicative
      of a working memory impairment per se), and caused a marked disruption of motor
      activity (lengthened response latencies, increased probability of omissions and
      decreased trials completed). Furthermore, the quaternary analogue, N
      methylscopolamine (0.150 mg/kg), affected the motor activity of rats to the same
      extent as scopolamine. Mecamylamine (1.0; 3.0 mg/kg) also interfered with motor
      activity and it slightly decreased the choice accuracy, which was not dependent
      on the delay. Although mecamylamine disrupted the performance of rats in the
      DNMTP task, the disruption was not as severe as that seen with scopolamine.
      Moreover, both scopolamine and mecamylamine augmented the slight impairment on
      the choice accuracy of 5,7-DHT lesioned rats, but this was non-mnemonic in
      character. We conclude that there is no evidence for any major interaction
      between the serotonergic system and muscarinic or nicotinic cholinergic
      mechanisms in working memory per se, but muscarinic and nicotinic receptor
      antagonists may act additively with the 5,7-DHT lesion to disrupt the choice
      accuracy of rats.

PMID- 9160846
TI  - Prior non-spatial pretraining eliminates sensorimotor disturbances and
      impairments in water maze learning caused by diazepam.
AB  - Diazepam has been reported to impair spatial learning in the water maze. This
      experiment reexamined this topic using control groups that had first been non
      spatially pretrained to familiarize them with the general behavioral strategies
      required in the water maze task. Naive rats given diazepam (0.5, 3.0, 6.0 mg/kg,
      IP) displayed dose-related maze acquisition impairments and sensorimotor
      disturbances (swimming in the periphery of the pool, deflecting off or swimming
      over the hidden platform, jumping off the platform when placed there after a
      trial, ataxia on a narrow wooden beam). The sensorimotor disturbances interfered
      with the acquisition of information about the spatial location of the platform,
      occurred in the absence of impairments in a subsequent visible platform task or
      swim speed, and correlated strongly with measures of acquisition. In contrast,
      the non-spatially pretrained groups did not exhibit sensorimotor disturbances in
      the water maze and acquired the maze task as rapidly under diazepam as control
      rats. The non-spatially pretrained groups continued to display diazepam-induced
      sensorimotor disturbances (ataxia) in a novel beam walking task. CGS8216 (10.0 or
      20.0 mg/kg), a benzodiazepine receptor antagonist, attenuated the effect of 3.0
      or 6.0 mg/kg diazepam in naive rats, suggesting that the effects of diazepam were
      mediated by benzodiazepine receptors. Occupancy of benzodiazepine receptors by
      diazepam does not prevent robust spatial learning in the water maze.

PMID- 9160847
TI  - Caffeine reinforcement: the role of withdrawal.
AB  - This study examined caffeine's acute and withdrawal effects in moderate caffeine
      consumers (mean = 379 mg/day caffeine) to compare the relative contributions each
      might have to caffeine reinforcement. Subjects were caffeine restricted on the
      night before each of three sessions, which generally occurred at weekly
      intervals; these restrictions lasted until the session was completed
      approximately 19 h later. During the first two sessions, subjects received either
      placebo or caffeine (each subject's average daily intake). These two conditions
      occurred using a double-blind, quasi-random, crossover design. At the end of each
      session subjects completed the POMS, a caffeine withdrawal questionnaire, and a
      Multiple-Choice Form on which subjects made a series of discrete choices between
      receiving the drug again or receiving varying amounts of money. This form also
      included negative money amounts to assess how much subjects would forfeit to
      avoid placebo (e.g., withdrawal symptoms after placebo). During the third
      session, one of the previous choices was randomly selected and the consequence of
      that choice was implemented. Placebo increased self-reported feelings of "worn
      out," "headache," and "flu-like feelings," and decreased "alert," "upset
      stomach," "helpful," and "well-being" relative to caffeine. On the Multiple
      Choice Forms, subjects chose to receive caffeine rather than an average of $0.38
      and to forfeit $2.51 to avoid receiving placebo again. "Headache" was
      significantly correlated with amount of money forfeited to avoid placebo. These
      results suggest that, under these conditions, choice of caffeine is more potently
      controlled by avoiding withdrawal than it is by the positive effects of caffeine.

PMID- 9160848
TI  - Unbiased cocaine conditioned place preferences (CPP) obscures conditioned
      locomotion, and nimodipine blockade of cocaine CPP is due to conditioned place
      aversions.
AB  - The effect of nimodipine (0, 0.1, 1.0 and 10 mg/kg, SC), a dihydropyridine L-type
      Ca2+ channel antagonist, on the establishment of cocaine-(10 mg/kg IP)
      conditioned place preferences (CPP) was investigated. Nimodipine produced
      conditioned place aversions (CPA) on its own; reductions in cocaine CPP are
      apparently due to this CPA. There is a high negative correlation between time
      spent in the CS+ compartment and the difference in locomotion rates between the
      CS+ and the non-drug (CS-) compartments, independent of drug effects. This
      relationship is responsible for an increased rate of locomotion observed in the
      CS- compartment in cocaine-conditioned rats. Analysis of covariance indicated
      that cocaine CPP occurred independently of cocaine's effects on locomotion.
      Furthermore, cocaine produces an increase in the rate of locomotion in the CS+
      compartment when time spent in this compartment is equated with time spent in the
      CS- compartment. This suggests that cocaine's effects on CPP and "conditioned"
      locomotion are due to separate mechanisms of action. On the other hand,
      nimodipine-induced place aversions and locomotor rates are not independent of
      each other, indicating a common mechanism of action, or that one is a consequence
      of the other. It is concluded that place preferences and place aversions can
      sometimes be secondary to compartment-specific locomotor changes, and locomotion
      effects can be confounded by differential times spent in each compartment. The
      relationships between these two behaviours must be controlled for before
      conclusions of CPP or CPA can be drawn in drug conditioning studies.

PMID- 9160849
TI  - Purine modulation of dizocilpine effects on spontaneous alternation.
AB  - The Y-maze was used to assess spontaneous alternation behaviour in mice to
      examine possible interactions between the N-methyl-D-aspartate receptor channel
      blocker dizocilpine and purine receptor agonists and antagonists. Scopolamine
      reduced spontaneous alternation. Dizocilpine also produced a dose-dependent
      reduction in alternation scores, which was accompanied by an increase in
      locomotion. The selective A1 adenosine receptor antagonist 8-cyclopentyl-1,3
      dipropylxanthine (CPX) had no effect when administered alone, or in combination
      with scopolamine. However, when co-administered with dizocilpine, CPX reversed
      both the deficit in alternation behaviour and also the increase in locomotion
      induced by dizocilpine. The A1 selective agonist N6-cyclopentyladenosine (CPA)
      had no effect on either locomotion or alternation scores when administered alone,
      but in combination with scopolamine, CPA attenuated the scopolamine-induced
      deficit. CPA had no significant effect on the dizocilpine-induced deficit. The A2
      selective agonist N6-[2-(3, 5-dimethoxyphenyl)-2(2-methylphenyl)-ethyl]adenosine
      (DPMA), had no effect on spontaneous alternation when administered alone, but did
      cause a depression of locomotion. DPMA had no significant effect when co
      administered with scopolamine, but reversed the deficit in spontaneous
      alternation, and the increase in locomotion induced by dizocilpine. The A2
      selective antagonist 3,7-dimethyl-1-propargylxanthine (DMPX) had no effect when
      given alone or in combination with scopolamine, but when co-administered with
      dizocilpine, DMPX reversed the reduction in spontaneous alternation caused by
      dizocilpine. It is concluded that dizocilpine has a detrimental effect on
      spontaneous alternation which is mediated partly by A1 and A2 adenosine
      receptors.

PMID- 9160850
TI  - Responses of neurons in dorsal striatum during amphetamine-induced focused
      stereotypy.
AB  - The phase of highly focused, repetitive behavior (stereotypy) induced by
      amphetamine in rats emerges after an initial period of locomotor activation. To
      assess the neuronal correlates of this behavioral transition, single-unit
      activity was recorded from the dorsal striatum of awake, unrestrained rats. Units
      were first characterized in terms of their responsiveness to spontaneous
      movement. Various types of motor-related neurons were identified. Some increased
      activity above resting baseline during specific movements such as forward
      locomotion or turning of the head, while others were excited during periods of
      general behavioral activation. Neurons that showed no consistent change in firing
      rate during overt movement were classified separately. Administration of 5.0
      mg/kg d-amphetamine caused a steady increase in the overall neuronal response
      through both the locomotor and stereotypy phases. An analysis of specific
      neuronal types, however, revealed distinct, phase-related shifts in firing rate.
      Locomotor-related neurons discharged rapidly during the early phase of the
      amphetamine response and then declined toward baseline as focused stereotypy
      emerged. Cells found to be excited primarily during head movements showed
      relatively small changes shortly after drug administration but increased markedly
      in conjunction with intense head-movement activity associated with focused
      stereotypy. Other neurons, which increased activity nonselectively to a wide
      range of movements, showed progressive increases in firing rate during both
      behavioral phases elicited by the drug. Subsequent administration of 1.0 mg/kg
      haloperidol typically reversed the neuronal changes and blocked amphetamine
      induced focused stereotypy. Nonmotor-related cells responded inconsistently to
      amphetamine, showing an inhibition, excitation, or no change in rate. Previous
      assessments of neuron-behavior relationships have shown that changes in motor
      related neuronal activity are not secondary to amphetamine-induced behavioral
      changes, though this finding may not apply in all cases. At doses capable of
      eliciting focused stereotypy, therefore, amphetamine appears to trigger a complex
      pattern of striatal activity that governs the behavioral response. This
      conclusion supports steadily increasing evidence that the role of striatal
      neurons in amphetamine-induced focused stereotypy is shaped by multiple synaptic
      mechanisms.

PMID- 9160851
TI  - Nicotine nasal spray and vapor inhaler: abuse liability assessment.
AB  - Acute subjective and physiological effects were examined to provide information
      relevant to abuse liability of new nicotine delivery systems. Subjects (n = 12)
      were overnight-deprived smokers who received 0, 4, 8 and 16 active puffs from
      nicotine-containing cigarettes (0.1 mg per puff), 0, 1, 2 or 4 nasal sprays (0.5
      mg nicotine per spray) and 0, 30, 60 and 120 vapor inhalations (estimated 0.013
      mg nicotine per inhalation) in a within-subject single blinded design. While
      smokers clearly liked cigarette puffs, there was much less evidence of liking
      produced by either nasal spray or vapor inhaler; only modest elevations on a
      measure of good drug effects were observed. The novel delivery products
      engendered unpleasant effects of burning throat and nose, watery eyes, runny
      nose, coughing and sneezing that might be expected to limit abuse liability.
      Nicotine plasma level and heart rate increase was dose-related for cigarettes and
      nasal spray but not for vapor inhaler, indicating limited nicotine delivery with
      the latter device. Overall, results are consistent with the conclusion that the
      nicotine nasal spray and vapor inhaler are of substantially lower abuse liability
      than cigarettes in experienced cigarette smokers receiving initial exposure to
      these products.

PMID- 9160852
TI  - Effects of histamine agents on methamphetamine-induced stereotyped behavior and
      behavioral sensitization in rats.
AB  - In this study, effects of histamine (HA) agents on methamphetamine (METH)-induced
      stereotyped behavior and behavioral sensitization were examined in rats.
      Pretreatment with a precursor of HA, L-histidine (750mg/kg), significantly
      inhibited the METH (3 mg/kg)-induced stereotyped behavior, whereas pretreatment
      with an inhibitor of HA synthesis, alpha-fluoromethylhistidine (FMH) (100 mg/kg),
      an H1 antagonist pyrilamine (5 mg/kg) or an H2 antagonist zolantidine (5 mg/kg)
      enhanced it. The inhibitory effect of L-histidine on METH-induced stereotyped
      behavior was significantly blocked by coadministration of pyrilamine and
      zolantidine, indicating that the effect is mediated through H1 and H2 receptors.
      Moreover, chronic treatment with METH (3 mg/kg) significantly enhanced
      stereotyped behavior at the rechallenge with METH (1 mg/kg). Chronic treatment
      with L-histidine (750 mg/kg) plus METH inhibited the METH-induced argumentation
      of stereotyped behavior, while that with FMH (100 mg/kg), pyrilamine (5 mg/kg) or
      zolantidine (5 mg/kg) potentiated it. These findings suggest that the HA neuron
      system has an inhibitory role in METH-induced stereotyped behavior and behavioral
      sensitization.

PMID- 9160853
TI  - Increase of 5-HT7 (serotonin-7) and 5-HT1A (serotonin-1A) receptor mRNA
      expression in rat hippocampus after adrenalectomy.
AB  - The brain 5-HT (serotonin) system and circulating corticosteroids are in close
      interaction and both are implicated in the pathogenesis of affective disorders.
      The 5-HT1A receptor is thought to play a major role in this relationship.
      However, the recently cloned 5-HT7 receptor may also be involved, given its
      pharmacological similarities to the 5-HT1A receptor and its high expression in
      corticolimbic structures. Using in situ hybridization histochemistry, we have
      investigated 5-HT7 and 5-HT1A receptor mRNA expression in selected areas of the
      rat brain 7 days post-adrenalectomy. 5-HT7 receptor mRNA was increased in CA1 and
      CA3b after adrenalectomy, with no alterations in other hippocampal subfields or
      in retrosplenial cortex. Adrenalectomy was associated with a marked increase of 5
      HT1A receptor mRNA in dentate gyrus, CA3 and CA2, but not in CA1, nor in the
      raphe. These data indicate that circulating adrenal steroids have a inhibitory
      role on the expression of hippocampal 5-HT7 receptors as well as 5-HT1A
      receptors, but the effect upon the two transcripts occurs in different subfields.
      The 5-HT7 receptor is an additional candidate for mediating the interactions
      between 5-HT and corticosteroids within the hippocampus.

PMID- 9160854
TI  - Contribution of caudal brainstem to d-fenfluramine anorexia.
AB  - Of the central 5-HT substrates that may mediate the anorexic actions of
      systemically administered d-fenfluramine (d-FEN), those in the forebrain have
      received the most attention. As a counterpoint to this forebrain focus, we
      evaluated the contribution of caudal brainstem substrates to the anorexic action
      of d-FEN. Two experimental protocols were employed. In one we compared the
      feeding response (intra-oral intake of 12.5% glucose) of intact and chronic
      supracollicular decerebrate (CD) rats to systemic administration of d-FEN. In the
      other, d-FEN was administered via fourth intracerebroventricular (ICV) injection
      to determine whether a dose-related suppression of intra-oral intake could be
      obtained. A dose-dependent suppression of intra-oral intake was obtained in the
      CD rat treated with d-FEN (0-8 mg/kg, delivered IP 20 min before testing). The
      threshold dose was two to three times higher in CD rats than in their intact
      controls, but the dynamic range of the dose-response curves of the two groups
      were overlapping with similar slopes of decline and with comparable maximal
      intake suppression. Fourth ICV administration of d-FEN in the intact rat yielded
      a dose-related suppression of intra-oral intake. Intake was also suppressed by
      fourth ICV d-FEN (30 mg) when rats drank 12.5% glucose solution from a spout. The
      reduced intra-oral intake following fourth ICV d-FEN treatment was partially
      attenuated by the systemic administration of the serotonin antagonist metergoline
      (0.4 mg/kg; IP). The CD results demonstrate the sufficiency of caudal brainstem
      receptors in mediating intake suppressive responses to systemic d-FEN. The fourth
      ICV results suggest further that 5-HT receptors in the caudal brainstem play a
      significant role in normal meal size control in the neurologically intact rat.

PMID- 9160855
TI  - Involvement of the alpha2-adrenergic system in polydipsia in schizophrenic
      patients: a pilot study.
AB  - Animal studies have suggested the involvement of the adrenergic system in
      drinking behavior. The present study investigated the involvement of the alpha2
      adrenergic system in the polydipsia of patients with chronic schizophrenia by use
      of an alpha2 agonist and an antagonist. Four patients with schizophrenic
      disorders accompanied by intermittent hyponatremia and polydipsia were the
      subjects of, and completed, this study. Drinking behavior was assessed by
      calculating the percent of maximum weight gain [PMWG: (maximum diurnal weight -
      standard weight) x 100/standard weight]. Standard weight was defined as body
      weight after 8 h of water restriction. Clonidine (75, 150, and 225 mg/day)
      increased the PMWG in a dose-dependent manner in the four subjects. In contrast,
      in three of the subjects, mianserin (30, 60, and 90 mg/day) decreased PMWG, and
      the severe polydipsia disappeared almost completely. These findings indicate
      clearly that the alpha2-adrenergic system is involved in the drinking behavior of
      schizophrenic patients. Mianserin appears to be clinically useful in treating
      such patients with polydipsia.

PMID- 9160856
TI  - Discriminative stimulus effects of apomorphine and 7-OH-DPAT: a potential role
      for dopamine D3 receptors.
AB  - Previous studies have reported that the non-selective dopamine agonist,
      apomorphine, can serve effectively as a discriminative stimulus in experimental
      animals, and evidence has been presented that this effect is mediated by dopamine
      D2 receptors. More recently, it has been found that another dopamine agonist, 7
      OH-DPAT, which has some selectivity for D3 receptors, also produces a
      discriminative cue in rats. The present study set out to make a direct comparison
      of the discriminative stimulus effects of these two compounds. Rats were trained
      to discriminate either apomorphine (0.05 mg/kg, SC) or 7-OH-DPAT (0.1 mg/kg, IP)
      from saline. Both discriminations were acquired but extended training was
      necessary. Cross generalisation occurred between the two compounds and both cues
      generalised to the dopamine agonists, quinpirole, quinelorane, PD 128207, and
      bromocriptine. When the potencies of these compounds to produce the apomorphine
      or 7-OH-DPAT cues were correlated with their potencies to produce D2 or D3
      functional responses in vitro (mitogenesis in transfected cells-results taken
      from the literature) stronger correlations with D3 than with D2 responses were
      observed. Both the cueing and the response rate-decreasing effects of apomorphine
      and 7-OH-DPAT were antagonised by the autoreceptor selective dopamine antagonist
      amisulpride, and sulpiride also antagonised the cues but without affecting
      response rates. In contrast, haloperidol blocked the cues but potentiated the
      response rate decreases. These results suggest that, at the doses used,
      apomorphine and 7-OH-DPAT produce similar discriminative stimuli, which may be
      mediated by presynaptically located dopamine D3 receptors.

PMID- 9160857
TI  - Reinstatement and spontaneous recovery of nicotine seeking in rats.
AB  - Reinstatement and spontaneous recovery of previously extinguished nicotine-taking
      behavior were examined in rats. Male subjects were trained to self-administer
      nicotine (30 microg/kg per infusion, IV; one 60-min session per day for 3 weeks).
      Extinction sessions were then given for 5-10 days during which saline was
      substituted for nicotine. Subsequently, in the first set of tests for nicotine
      seeking, the reinstatement of lever presses that previously delivered nicotine
      was examined after priming injections of saline and nicotine (75, 150 and 300
      microg/kg, SC; and 30 and 60 microg/kg, IV). In the second set of tests for
      nicotine-seeking, rats were tested after an additional 21-day drug-free period
      during which they were not exposed to the self-administration chambers (a test
      for the spontaneous recovery of drug seeking), and after priming injections of
      nicotine (150 and 300 microg/kg, SC). Reinstatement of extinguished food
      reinforced behavior after exposure to nicotine was also determined. Priming
      injections of nicotine reinstated nicotine seeking regardless of the route of
      administration. In addition, previously extinguished nicotine seeking recovered
      spontaneously after a 21-day period during which rats were not exposed to the
      drug-taking environment. Nicotine also reinstated extinguished food-reinforced
      behavior in rats with a history of nicotine self-administration, but not in drug
      naive rats. The present results extend previous work with opioid and stimulant
      drugs on reinstatement of drug seeking by the self-administered drug. It also
      appears that, as with other positive reinforcers, the mere passage of time is a
      sufficient condition for the spontaneous recovery of extinguished nicotine
      seeking.

PMID- 9160858
TI  - Substitution of the selective serotonin reuptake inhibitors fluoxetine and
      paroxetine for the discriminative stimulus effects of ethanol in rats.
AB  - Rats trained to discriminate ethanol (EtOH, 1 g/kg IP) from saline in a two-lever
      procedure completely generalized to the selective serotonin reuptake inhibitors
      (SSRIs) fluoxetine and paroxetine. Substitution of fluoxetine was completely
      blocked by the selective 5-HT2A receptor antagonist MDL 100,907 and not affected
      by the selective 5-HT1A receptor antagonist WAY-100635. It is suggested that the
      previously reported effectiveness of SSRIs in reducing EtOH consumption could be
      based on similarities in discriminative stimulus effects of SSRIs and EtOH.
      Stimulation of 5-HT2A receptors may underlie these stimulus similarities and
      contribute to the EtOH intake-reducing effects of SSRIs.

PMID- 9160860
TI  - The origins of myocardial substrate utilization from an evolutionary perspective:
      the enduring role of glucose in energy metabolism.

PMID- 9160859
TI  - Intracrine and autocrine effects of basic fibroblast growth factor in vascular
      smooth muscle cells.
AB  - In order to elucidate the effects of the different basic fibroblast growth factor
      (bFGF) isoforms on vascular smooth muscle, we examined aorta-derived vascular
      smooth muscle cells from transgenic mice expressing the human isoforms of bFGF.
      Four cell lines were examined from mice in which transgene expression was driven
      by the ubiquitous phosphoglycerate kinase promoter. Overexpression and cellular
      localization was confirmed by Western blot analysis in vascular smooth muscle
      cells from mice expressing: all four human bFGF isoforms (24, 22, 21, and 18
      kDa); all three nuclear targeted isoforms (24, 22, and 21 kDa); only the 24 kDa
      isoform; and the only secreted/non-nuclear targeted isoform, 18 kDa. All lines
      showed approximate four-fold increases in bFGF expression, nuclear localization
      of all nuclear targeted bFGF isoforms, and cytosolic localization of only the 18
      kDa bFGF. Measurement of [3H]thymidine incorporation into quiescent cells
      stimulated with increasing concentrations of serum, showed increased DNA
      synthesis in cell lines expressing any bFGF isoform when compared to non
      transgenic control cells, and a further increase in DNA synthesis in cells
      expressing the nuclear targeted isoforms (24, 22, and 21 kDa) over the 18 kDa
      bFGF expressing cell line at any concentration of serum. All cells showed equal
      label incorporation when stimulated with 10 ng/ml of platelet-derived growth
      factor confirming an equal potential for DNA synthesis. Neutralizing the bFGF
      antibody markedly decreased serum-stimulated DNA synthesis, but only in the cell
      lines overexpressing the secreted/non-nuclear targeted 18 kDa isoform. These
      results suggest amplification of DNA synthesis through synergistic intracrine and
      autocrine effects of the nuclear targeted and non-nuclear targeted bFGF isoforms
      in vascular smooth muscle cells.

PMID- 9160861
TI  - Role of low molecular weight iron in functional preconditioning of the isolated
      rat heart.
AB  - Post-ischemic contractile dysfunction in the heart may be due to oxygen-derived
      free radicals catalyzed by low molecular weight iron (lmw Fe), which is thought
      to accumulate during ischemia and reperfusion. We tested the hypothesis that
      functional preconditioning with transient ischemia in the rat heart may be due to
      decreasing the myocardial lmw Fe pool, and consequently free radicals during
      ischemia or reperfusion. Hearts were preconditioned with two 5-min episodes of
      ischemia followed by 5 min of reperfusion. The lmw Fe pool of pre-ischemic hearts
      was 172 +/- 13pmol/mg protein. After 40 min of prolonged ischemia, the lmw Fe
      contents were 176 +/- 25 and 127 +/- 13 pmol/mg for non-conditioned and
      preconditioned hearts, respectively (P=N.S.). After 10 min of reperfusion, the
      lmw Fe contents were 246 +/- 26 and 228 +/- 23 pmol/mg protein, respectively
      (P=N.S.). We next tested the ability of deferoxamine, an iron chelator, to mimic
      functional preconditioning. The percentage recoveries of heart rate x developed
      pressure after 40 min of ischemia and 30 min of reperfusion were 38 +/- 6 and 25
      +/- 5 for non-conditioned and deferoxamine-treated hearts, respectively (P=N.S.).
      We further tested the hypothesis by determining if iron-overloading by dietary
      enhancement and weekly iron injections would exacerbate post-ischemic contractile
      dysfunction and attenuate functional preconditioning with ischemia. The total
      iron contents of the high iron and normal groups were 10.3 +/- 0.6 and 4.4 +/-
      0.2 nmol/mg protein (P<0.001). Percentage recoveries of heart rate x developed
      pressure were 36 +/- 6 and 33 +/- 5 for non-conditioned hearts in the high iron
      and normal iron groups, respectively (P=N.S.). Percentage recoveries of heart
      rate x developed pressure were 58 +/- 5 and 68 +/- 6 for ischemically
      preconditioned hearts in the high and normal iron groups, respectively (P= N.S.).
      The results suggest that functional preconditioning in the rat heart is not due
      to attenuation lmw Fe accumulation.

PMID- 9160862
TI  - Early changes in the functions of cardiac sarcoplasmic reticulum in volume
      overloaded cardiac hypertrophy in rats.
AB  - By sequestering activator calcium, the sarcoplasmic reticulum (SR) plays the
      central role in the excitation-contraction (E-C) cycle of cardiac muscle. Hence,
      functional changes in the SR in diseased myocardium might critically determine
      its mechanical characteristics. Previously, we demonstrated that both Ca2+
      release and uptake were increased in SR isolated from hearts showing compensatory
      left ventricular (LV) hypertrophy taken from pressure-overloaded rats. However,
      it has not been elucidated whether such alterations also occur in the volume
      overloaded myocardium. Rats in which volume-overloaded hypertrophy had been
      induced by aortocaval shunt 12 weeks prior to the investigation were compared to
      sham-operated controls in terms of SR Ca2+ uptake and release, and density of
      Ca2+ releasing channels (ryanodine receptors, RyR). Isometric tension and
      intracellular Ca2+ transients were also measured using the bioluminescent Ca2+
      indicator, aequorin, in isolated LV papillary muscles. The extent of hypertrophy
      was verified by measuring the ratio of biventricular weight to body weight. In
      vivo, the aortocaval shunt rats showed normal LV contractility and slightly
      depressed LV relaxation, indicating a compensatory (adaptive) stage of LV
      function. In contrast, Ca2+ release, uptake, and maximal number of [3H]-ryanodine
      binding sites were all significantly lower in aortocaval shunt rats than in
      controls. Both the Ca2+ transients and isometric relaxation of the isolated
      myocardium were significantly prolonged in aortocaval shunt rats, though their
      amplitudes were similar in the two groups. Thus, the volume-overloaded cardiac
      hypertrophy, even at its hemodynamically compensatory (adaptive) stage, (i) was
      accompanied by abnormal Ca2+ handling, as indicated by prolonged intracellular
      Ca2+ transients and isometric tension traces, (ii) seems to involve subcellular
      mechanisms related to decreases in SR Ca2+ release and uptake functions, as well
      as to a decrease in the number of RyR. Therefore, changes in the intracellular
      processes underlying cardiac E-C coupling, including SR function, precede the
      development of this type of heart disease.

PMID- 9160863
TI  - In vivo role of glucocorticoids in barotrauma vascular repair and fibrosis.
AB  - To determine the important repair events leading to vascular collagen
      accumulation following barotrauma, in vivo changes were assessed during
      dexamethasone (DEX) treatment, as well as physiological healing.
      Hypercholesterolemic rabbits underwent bilateral iliac artery endothelial
      denudation, followed by angioplasty. Messenger ribonucleic acid (RNA)
      (procollagen types I, III and transforming growth factor [TGF]beta1), and bio
      histometric composition of iliac arteries of animals treated with DEX (2, 7 and 7
      days; 1 mg/kg1/day1), were compared to that in controls 2, 7 and 30 days after
      angioplasty. Type I and III procollagen mRNA transcripts were up-regulated
      following injury in either group. Similarly, TGFbeta1 mRNA levels were also
      elevated; however, treatment with DEX led to down-regulation at day 30 post
      angioplasty. Linear regression and correlation of the densitometric ratios of
      procollagen alpha1(I) and TGFbeta1 mRNA during repair were observed significantly
      in either group (DEX-treated, r2= 0.84; non-treated, r2=0.79). Biochemically
      derived total vascular RNA concentration decreased transiently (7 days), with DEX
      treatment (P = 0.003). Arterial lumen cross-sectional area was reduced between
      days 2 and 30 (P=<0.02), accompanied by an increase in fibrillar collagen
      concentration in both groups of animals post-angioplasty. These results suggest
      that during barotrauma repair, administration of DEX (approximately 1 week), does
      not affect vascular intimal hyperplasia or fibrosis, and that despite treatment,
      significant production of type I procollagen mRNA continues, influencing
      subsequent collagen deposition. The data also confirm a strong correlation
      between TGFbeta1 and type I procollagen mRNA expression, and modestly with type
      III procollagen during post-angioplasty repair.

PMID- 9160864
TI  - Pinacidil but not nicorandil opens ATP-sensitive K+ channels and protects against
      simulated ischemia in rabbit myocytes.
AB  - It has been proposed that ischemic preconditioning involves the regulation of ATP
      sensitive potassium (K(ATP)) channels. The evidence is based largely on the
      ability of certain K(ATP) channel modulators to modify the protection in the
      various models of preconditioning. This study has investigated how two K(ATP)
      channel openers, pinacidil and nicorandil, affect both membrane currents and
      viability in isolated and ischemic rabbit cardiomyocytes. We used the whole-cell
      recording technique and in separate experiments viability was assessed by
      exposure to these drugs during ischemia. Pinacidil (50 micromol/l) increased
      K(ATP) current approximately four-fold in isolated cardiomyocytes. This increase
      reversed rapidly after treatment with the K(ATP) channel blocker glibenclamide
      (200 nmol/l). After simulated ischemia, pinacidil protected cardiomyocytes (the
      area under cell-death curve was 29.5 +/- 1.1% x h) which was significantly less
      than that in control (46.9 +/- 2.0% x h). The protection from pinacidil could be
      completely eliminated by pretreatment with 10 microM glibenclamide (46.9 +/- 2.0%
      x h). In contrast, nicorandil (1 mmol/l), which opens K(ATP) channels in some
      tissues, caused no detectable effect on the K(ATP) current. Similarly, nicorandil
      did not produce cardioprotection. These results indicate that pinacidil and
      nicorandil have very different effects on rabbit cardiomyocyte K(ATP) channels.
      Furthermore, because protection correlated with the ability of the agent to open
      the channel, they support a role for K(ATP) channels in preconditioning.

PMID- 9160865
TI  - Interaction between Na+ and H+ ions on Na-H exchange in sheep cardiac Purkinje
      fibers.
AB  - The interaction between Na+ and H+ ions upon Na-H exchange (NHE) was examined in
      sheep cardiac Purkinje fibers. Acid equivalent fluxes through NHE were examined
      using recordings of intracellular pH and Na+ in isolated preparations measured
      with ion selective microelectrodes. The extent of acid-extrusion by NHE was
      estimated from pH(i) recovery-rate, multiplied by beta(i) (intracellular
      buffering power) in response to an internal acid load induced by 20 mm NH4Cl
      removal (nominally HCO3- free media). A mixed inhibitory effect was found of
      extracellular H+ on external Na+-activation of NHE (i.e. an increase, at low
      pH(o), in the apparent Michaelis constant for external Na+ ions [K(Nao)(0.5)] and
      a decrease in the maximum transport rate [V(Nao)(max)]). In addition, we
      confirmed that the stoichiometry of Na(o) binding is unaffected by the pH(o)
      (between 7.5 and 6.5), showing a Hill coefficient close to one. The interaction
      between Na+ and H+ ions at the internal face of the cardiac NHE was also studied.
      Our evidence suggests that an increase in the intracellular Na+ ion concentration
      ([Na+]i) inhibits acid efflux and that this inhibition can be approximated by the
      decrease in thermodynamic driving force caused by reducing the transmembrane Na+
      gradient. It appears, however, that small variations in [Na+]i from the normal
      resting level (intracellular sodium activity, a(i)Na = 7 to 13 mm) have little or
      no effect on acid efflux, suggesting that variation of a(i)Na is not a
      physiologically important controller of NHE activity in heart.

PMID- 9160866
TI  - Mechanical load enhances the stimulatory effect of serum growth factors on
      cardiac fibroblast procollagen synthesis.
AB  - The mechanical environment is a key determinant of cellular activity in many
      tissues. In the cardiovascular system it plays a role in tissue remodelling
      during both development and disease. In the heart changes in mechanical tension
      stimulate myocyte hypertrophy and fibroblast collagen synthesis. To elucidate the
      mechanisms for the latter response, we determined the direct effect of mechanical
      load on cardiac fibroblast activity. Primary cultures of fetal rat cardiac
      fibroblasts were mechanically loaded in the presence or absence of fetal calf
      serum or growth factors, and the effects on fibroblast replication and
      procollagen metabolism and gene expression determined. Procollagen synthesis was
      increased by 99.7 +/- 4.3% in response to mechanical load and 10% fetal calf
      serum, compared to 10% fetal calf serum control (P<0.01) after 48 h. Procollagen
      alpha1(I) steady-state mRNA levels were increased two-fold. No effect was
      observed in the absence of serum. Transforming growth factor beta1 and insulin
      like growth factor 1 have been demonstrated to stimulate procollagen metabolism
      by these cells. Mechanical load enhanced the response to these growth factors,
      stimulating alpha1(I) mRNA levels by 4.3 and three-fold, respectively, above
      growth factor alone controls. These results demonstrate a synergistic effect on
      procollagen gene expression and metabolism by mechanical load and profibrotic
      growth factors. Since these factors are released during the development of
      cardiac hypertrophy, interactions between the mechanical environment and these
      polypeptides may provide a mechanism for enhanced collagen deposition in the
      heart.

PMID- 9160867
TI  - Dedifferentiated human ventricular cardiac myocytes express inducible nitric
      oxide synthase mRNA but not protein in response to IL-1, TNF, IFNgamma, and LPS.
AB  - There is evidence that nitric oxide (NO) may mediate some of the functional
      myocardial changes caused by bacterial LPS and inflammatory cytokines. The
      expression of the inflammatory or inducible NO synthase (iNOS) in human cardiac
      myocytes, however, has not been well characterized. Therefore, we treated
      cultured, dedifferentiated human ventricular cardiac myocytes with the
      combination of TNF-alpha (500 U/ml), IL-1beta (30U/ml), IFNgamma (100 U/ml), and
      LPS (E.coli 0111:B4, 10 microg/ml). Northern blot analysis revealed a
      approximately 4.5 kb transcript for inducible NOS (iNOS) in the stimulated human
      heart cells but not in untreated cells. RT-PCR confirmed that iNOS mRNA was only
      present in stimulated cells. However, treatment of the myocytes for up to 96 h
      with cytokines and LPS did not result in NO synthesis as measured by nitrite +
      nitrate accumulation in the culture medium, and no iNOS enzymatic activity could
      be detected in the cell lysates. Western blot analysis failed to detect iNOS
      protein. Thus, despite high and persistent levels of iNOS mRNA in cytokine
      treated cells, iNOS protein was absent in this experimental model. GTP
      cyclohydrolase I was induced both at the mRNA and protein levels and resulted in
      increased biopterin levels, indicating sufficient amounts of the cofactor
      tetrahydrobiopterin (BH4) were present, and that the failure to express an
      inducible protein was specific to iNOS. To determine if the absence of iNOS
      protein was due to a novel cardiac iNOS gene or modified iNOS transcript in human
      myocytes, we cloned an iNOS cDNA from cytokine-treated myocytes. Sequencing and
      expression of the clone revealed a functional iNOS cDNA with >99% identity to
      other human iNOS cDNA clones. When human cardiac cells were transduced with a
      retroviral vector carrying only the coding region of the human hepatocyte iNOS
      cDNA, both iNOS mRNA and protein could be detected. In conclusion, these cells
      derived from cultured human cardiac myocytes lacked the capacity to express an
      endogenous iNOS protein, the basis of which appears to be a cell-specific
      suppression or failure of iNOS translation.

PMID- 9160868
TI  - The role of Na+-H+ exchange occurring during hypoxia in the genesis of
      reoxygenation-induced myocardial oedema.
AB  - To investigate the role of Na(+)-H+ exchange occurring during hypoxia in the
      genesis of reoxygenation-induced myocardial oedema, isolated perfused rat hearts
      were submitted to 40 min of hypoxia and 90 min of reoxygenation. The influence of
      three factors on myocardial water content was analysed according to a 2 x 2 x 2
      factorial design; the hearts were perfused at either pH = 7.4 or pH = 7.0, with
      either HCO3- buffer or HCO3(-)-free HEPES buffer, and in half of the experiments
      the hypoxic buffer contained HOE642 6.7 micromol/l. In an additional group, 160
      min of normoxia resulted in no lactate dehydrogenase (LDH) release and in a 35.8%
      increase in myocardial water, independently of pH and of the presence of HCO3- in
      the buffer. In hearts perfused at pH = 7.4, reoxygenation induced LDH release
      which was reduced (P<0.05) by HOE642 by 20.1%, by HCO3(-)-free perfusion by
      57.5%, and by the combination of both by 91.2%. Reoxygenation also induced severe
      myocardial oedema (26.3% increase (P<0.05) respect to normoxia). HOE642 reduced
      (P<0.05) reoxygenation oedema by 15.7%, HCO3(-)-free perfusion by 8.9%, and the
      combination of both by 24.6%. The effects of HCO3(-)-free perfusion could be
      mimicked in HCO3(-)-perfused hearts by blocking Na(+)-HCO3- cotransport with 4-4'
      dibenzanidostilbene-2,2'-disulphonic acid (DIDS). The beneficial and additive
      effects of HOE642 and of HCO3(-)-free perfusion on oedema were not a mere
      consequence of their protective effects against the oxygen paradox, since they
      were observed in groups perfused at pH= 7.0, a condition which virtually
      prevented LDH release without preventing oedema (19.0% increase in myocardial
      water). Thus, reoxygenation-induced myocardial oedema may occur in the absence of
      necrosis, and is largely determined by Na+ gain during hypoxia via Na(+)-H+
      exchange and Na(+)-HCO3- cotransport.

PMID- 9160869
TI  - Changes in essential myosin light chain isoform expression provide a molecular
      basis for isometric force regulation in the failing human heart.
AB  - We investigated the effects of the expression of myosin light chain (MLC)
      isoforms on the Ca2+ sensitivity of isometric force production of demembranated
      (skinned) fibers of papillary muscle from the left ventricle of three groups:
      patients with ischemic cardiomyopathy, patients with dilated cardiomyopathy (NYHA
      IV) and normal human hearts. Expression and phosphorylation of the
      phosphorylatable MLC isoforms (MLC-2) was equal within all three groups. However,
      72% of the patients investigated in this study expressed the atrial essential MLC
      (ALC-1) in addition to the essential ventricular MLC (VLC-1) ranging between 2.4%
      and 10.3%. Using fibers from failing hearts, we observed a significant positive
      correlation between ALC-1 and Ca2+ sensitivity in that the higher the ALC-1
      expression the higher the Ca2(+)-sensitivity: pCa50 (Ca2+ required for half
      maximal force production) was 5.87 without ALC-1 and 6.08 with 10.3% ALC-1.
      Fibers from a normal heart (no ALC-1) revealed a pCa50 of 5.85. Isoform and
      phosphorylation patterns of tropomyosin and troponin I remained unchanged in the
      patients and normal hearts. Our results suggest that Ca2+ responsiveness and
      force development of the human heart is regulated by the expression of different
      MLC-1 isoforms.

PMID- 9160870
TI  - XTT-colorimetric assay as a marker of viability in cryoprocessed cardiac valve.
AB  - This study sought to evaluate the use of tetrazolium salt XTT reduction as an
      indicator of valvular viability in a cryoprocessed porcine cardiac homograft
      model. The XTT tetrazolium assays was based on the metabolic reduction of Sodium
      3'-[1-(phenylamino-carbonyl)-3,4-Tetrazolium]-bis(4-methoxy-6-nitro) benzene
      sulfonic acid hydrate. The relationship between XTT reduction and: (1) leaflet
      tissue with various weight (n = 24); (2) morphometric evaluation (n = 30); (3)
      cadaveric ischemic intervals (n = 30); (4) freeze-thawing (n = 30) has been
      studied. The measurement of XTT reduction were significantly correlated with the
      weight of cardiac leaflets, in the range of 30 to 180mg (y=0.015x-0.063; r=0.99).
      Compared to morphometry of valvular damage, the reduction of mitochondrial
      enzymatic activity in cardiac leaflets was correlated with matrix cells without
      irreversible damage (r=0.89, P<0.005). The depletion of XTT reduction occurred
      dependent of ischemic time intervals. In general, freeze-thawing reduced more
      than 20% activity of mitochondrial dehydrogenase. We concluded that XTT
      tetrazolium assay is highly sensitive to determine valvular injury. The study
      demonstrated its potential for testing of cryopreserved cardiac valve.

PMID- 9160871
TI  - Beneficial effects of a nitric oxide donor on recovery of contractile function
      following brief hypoxia in isolated rat heart.
AB  - Brief myocardial hypoxia causes both systolic and diastolic dysfunction, the
      latter often persisting during re-oxygenation. The underlying mechanisms may
      involve cytosolic Ca2+ overload as well as altered myofilament properties. Recent
      studies show that nitric oxide enhances myocardial relaxation via a cGMP-induced
      reduction in myofilament response to Ca2+. We studied the effects of pretreatment
      with a nitric oxide donor, sodium nitroprusside (0.1-1 microM) on the response to
      5 min hypoxia in isovolumic rat hearts perfused at constant coronary flow. Left
      ventricular relaxation was assessed by an exponential time constant of pressure
      fall. Sodium nitroprusside reduced the depression of peak left ventricular
      pressure and peak dP/dt during hypoxia, and improved left ventricular relaxation
      both during hypoxia and re-oxygenation. Similar results were observed with a Ca2+
      antagonist, nicardipine (10 nM). However, adenosine (400 nM), which reduced
      coronary perfusion pressure to a similar extent as the other two drugs, failed to
      improve left ventricular function. Addition of sodium nitroprusside or
      nicardipine at re-oxygenation did not improve relaxation, but instead impaired
      recovery of peak left ventricular pressure. These results suggest that exogenous
      nitric oxide improves LV contractile function, in particular relaxation, during
      brief hypoxia-re-oxygenation independent of changes in coronary flow or coronary
      perfusion pressure. Its failure to be protective if administered only during re
      oxygenation suggests that its action does not involve an anti-oxidant effect.

PMID- 9160872
TI  - Differential regulation of glucose and glycogen metabolism in vascular smooth
      muscle by exogenous substrates.
AB  - The aim of this study was to determine whether the pathways of glycolysis and
      glycogenolysis can be independently modulated by the provision of acetate or
      pyruvate as exogenous substrates. Hog carotid artery segments were allowed to
      replete glycogen stores to over 6 micromol/g of new 13C-labeled glycogen by
      incubation at 37 degrees C with 5 mM [1-13C]glucose for 6-16 h and then were
      isometrically contracted for 3 h with 80 mM KCl in the presence of 5 mM [2
      13C]glucose and either 2 mM sodium acetate or 5 mM sodium pyruvate. Measurements
      were made of total lactate production, glucose utilization, glycogen utilization,
      isometric force, [2-13C]lactate and [3-13C]lactate production. Compared to
      experiments with glucose as the sole exogenous substrate, provision of pyruvate
      significantly decreased glucose utilization (by 28%) but insignificantly
      decreased glycogen utilization. In contrast, provision of acetate resulted in a
      statistically insignificant decrease in glucose utilization (by 23%) and an
      increase in glycogen utilization (by 20%). The fraction of [3-13C]pyruvate
      derived from glycogen that was converted to [3-13C]lactate was significantly
      decreased in the presence of acetate despite the enhanced glycogen utilization.
      Despite these alterations in cellular energy balance, isometric force generation
      and maintenance was similar for all experimental groups. This differential
      regulation of glycolysis and glycogenolysis may either reflect the
      compartmentation of these pathways or suggest a novel regulation of carbohydrate
      metabolism in vivo.

PMID- 9160873
TI  - Abnormal immunostaining for dystrophin in isoproterenol-induced acute myocardial
      injury in rats: evidence for change in dystrophin in the absence of genetic
      defect.
AB  - Abnormalities in the gene for Duchenne muscular dystrophy produce skeletal and
      myocardial changes, by impairing dystrophin production in patients with Duchenne
      and Becker muscular dystrophy. However, it is not known whether myocardial
      dystrophin may be altered in patients with other heart diseases. To investigate
      whether changes in myocardial dystrophin may be induced by acute myocardial
      injury, the immunostaining patterns of myocardial dystrophin were examined,
      together with those of myocardial actin, in rats with isoproterenol-induced
      myocardial damage. Hearts were excised at 6, 12, 24 and 48 h, and 1 and 4 weeks
      after the subcutaneous administration of 100 mg/kg of isoproterenol. Frozen
      serial sections were prepared for haematoxylin and eosin staining, and for
      immunostaining for dystrophin and actin. The immunostaining patterns of actin
      were used as an indicator of cell injury. The myocardial cells observed were
      classified into four types, according to staining pattern: normal for both actin
      and dystrophin (Type 1): normal for actin, but abnormal for dystrophin (Type 2);
      abnormal for actin, but normal for dystrophin (Type 3); and abnormal for both
      actin and dsytrophin (Type 4). The percentage of myocardial cells with abnormal
      staining (Types 2, 3 and 4) at 6, 12, 24 and 48 h after isoproterenol injection
      was 22.4, 12.6, 16.0 and 2.4%, respectively; most cells were Types 3 and 4. One
      week after injection or later, no Type 3 or 4 cells were detected, while the
      percentages of Type 2 cells were 2.7% for 1 week and 2.2% for 4 weeks,
      significantly higher than the corresponding value in the control group. In
      conclusion, changes in myocardial dystrophin may occur in isoproterenol-induced
      myocardial injury in rats.

PMID- 9160874
TI  - The modulation of pacing-induced changes in intracellular sodium levels by
      extracellular Ca2+ in isolated perfused rat hearts.
AB  - This study demonstrates the inverse relationship between extracellular free
      calcium ([Ca(o)]f) and intracellular sodium ([Na(i)]) in isolated perfused rat
      hearts and thus supports the role of [Na(i)] in the "calcium paradox". It also
      shows that the extent of the increase in [Na(i)] (delta[Na(i)]), and the extent
      of the decrease in left ventricular developed pressure (deltaLVDP) in isolated
      perfused rat hearts, induced by pacing, is modulated by [Ca(o)]f. At low (0.24
      mM) as well as normal (1.15 mM) [Ca(o)]f, [Na(i)] increased with pacing,
      progressively and significantly (P<0.01 and P<0.05, respectively), reaching a
      maximum of 12.56 +/- 0.46 and 9.22 +/- 0.16 mM at 500 beats/min, respectively. At
      high [Ca(o)]f (2.2 mM), however, no pacing-induced increase in [Na(i)] was
      observed. Simultaneously, within the pacing range of 250-500 beats/min, the
      interval-force relationship was negative for all [Ca(o)]f. With decreasing
      [Ca(o)]f, a gradually increasing delta[Na(i)] was induced. We hypothesise that a
      [Ca(o)]f-dependent Na-Ca exchanger activity modulates Na+ uptake, and thus
      baseline [Na(i)]. During incremental pacing, the increase in pacing rate induces
      a [Ca(o)]f-dependent delta[Na(i)], which may interact further with the
      sarcolemmal Na-Ca exchanger activity. As a result, both baseline [Na(i)] and the
      pacing-induced, [Ca(o)]f-dependent delta[Na(i)] modulate the net Ca2+ uptake, and
      thus SR Ca, in a manner that results in a modulated left ventricular force
      development.

PMID- 9160875
TI  - Cardiac calcium release channel (ryanodine receptor) in control and
      cardiomyopathic human hearts: mRNA and protein contents are differentially
      regulated.
AB  - Abnormal intracellular calcium handling in cardiomyopathic human hearts has been
      associated with an impaired function of the sarcoplasmic reticulum, but previous
      reports on the gene expression of the ryanodine receptors (Ry2) are
      contradictory. We measured the mRNA levels, the protein levels and the number of
      high affinity [3H]ryanodine binding sites in the left ventricle of non-failing (n
      = 9) and failing human hearts [idiopathic dilated (IDCM n = 16), ischemic (ICM n
      = 7) or mixed (MCM n = 8) cardiomyopathies]. Ry2 mRNA levels were significantly
      reduced in IDCM (-30%) and unchanged in MCM and ICM and Ry2 protein levels were
      similar. In contrast, we observed a two-fold increase in the number of high
      affinity Ry2 (B(max) = 0.43 +/- 0.11 v 0.22 +/- 0.13 pmol/mg protein,
      respectively; P<0.01) and an unchanged K(d). Furthermore, levels of myosin heavy
      chain mRNA and protein per g of tissue were similar in failing and non-failing
      hearts, suggesting that the observed differences in Ry2 are not caused by the
      increase in fibrosis in failing heart. Therefore, the dissociation between the
      two-fold increase in the number of high affinity ryanodine receptors observed in
      all failing hearts and the slightly decreased mRNA level or unchanged protein
      level suggests that the ryanodine binding properties are affected in failing
      myocardium and that such modifications rather than a change in gene expression
      alter the channel activity and could contribute to abnormalities in intracellular
      Ca2+ handling.

PMID- 9160876
TI  - Isoform-specific regulation of adenylyl cyclase by oxidized catecholamines.
AB  - Both epinephrine and manganese are known to stimulate cAMP production in cardiac
      homogenates. When added together, however, they inhibited adenylyl cyclase
      catalytic activity. Type V adenylyl cyclase, the major isoform in the heart, was
      also inhibited when an increasing concentration of epinephrine was added in the
      presence of manganese. Inhibition was not dependent on the condition of
      stimulation or preparation of the enzyme. However, this inhibition was abolished
      in the presence of anti-oxidant. Other catecholamines, including dopamine and
      isoproterenol, as well as adrenochrome, an oxidized product of epinephrine,
      similarly inhibited the activity of this enzyme. Kinetic analyses revealed that
      the K(m) for the substrate ATP was unchanged, but the V(max) was significantly
      decreased. In contrast, type II adenylyl cyclase, a non-cardiac isoform, was
      resistant to such inhibition by adrenochrome and was somewhat stimulated by it.
      Thus, catecholamines, when oxidized, directly interacted with adenylyl cyclase in
      an isoform-specific manner in the absence of G proteins. Our findings suggest
      that adenylyl cyclase isoforms have different sensitivity to various stresses,
      including oxidative stress.

PMID- 9160877
TI  - Use of the MTT assay in adult ventricular cardiomyocytes to assess viability:
      effects of adenosine and potassium on cellular survival.
AB  - This study used the colorimetric MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide)] assay to assess cell viability in isolated quiescent adult
      guinea-pig ventricular myocytes exposed to different insults or cardioprotective
      conditions, including adenosine and hyperkalemic-cardioplegia. Optical density
      (OD), reflecting intracellular reduction of MTT into formazan pigment formation,
      was a function of the number of viable cells (coefficient of linear correlation
      approximately 0.99), with MTT reduction preferentially carried out by rod-shaped
      cardiomyocytes (absorbance at 1.009 +/- 0.013 and 0.006 +/- 0.001 OD units for
      populations containing 50 and 0% of rod-shaped cells). Following prolonged
      mechanical (pressure of 1 lb/min for 40 min), chemical (10% DMSO or ethanol) or
      hypoxic injury (N2-saturated solution), the MTT reductase activity reflected
      reduction in the number of viable cells by 87%, >50%, and 77%, respectively. In
      cardiomyocytes exposed to a 40 min hypoxia (with CO2), the MTT reductase activity
      was 0.056 +/- 0.009 in the absence, and 0.074 +/- 0.008 OD units in the presence
      of adenosine (1 mM), i.e. adenosine reduced the number of non-viable cells. Also,
      the MTT assay revealed that the effect of potassium-containing solutions (16 and
      32 mM K+) on cellular viability may depend on the extent of insult imposed on
      cardiomyocytes; i.e. a approximately 24% and 49% increase under mild hypoxia
      (0.03% CO2), or an 18% decrease in cell viability under severe hypoxia (N2) in
      pre-injured cells. Thus, the MTT assay used to assess viability of isolated adult
      cardiomyocytes revealed a direct cytoprotective effect of adenosine and
      hyperkalemic-cardioplegia by promoting cell survival under certain conditions in
      vitro.

PMID- 9160878
TI  - K(ATP) channels contribute to the cardioprotection of preconditioning independent
      of anaesthetics in rabbit hearts.
AB  - The contribution of ATP sensitive potassium (K(ATP)) channels to the infarct-size
      limiting effect of preconditioning is considered to be anaesthetic-dependent in
      the rabbit heart. It has previously been reported that ischaemic preconditioning
      prevents ischaemia-induced reductions in activities of sarcolemmal adenylate
      cyclase (AC) and Na+, K(+)-ATPase. Anaesthetic dependency of the role of K(ATP)
      channels in the preservation of these enzyme activities, induced by ischaemic
      preconditioning, as well as that induced by activation of A1-adenosine receptors,
      was examined in rabbits anaesthetized with either pentobarbital or ketamine
      xylazine and subjected to 20 min of regional ischaemia. Adenylate cyclase and
      Na+, K(+)-ATPase activities were lower in the ischaemic than in the non-ischaemic
      region of the hearts in control rabbits, but not in animals subjected to
      ischaemic preconditioning, or those pretreated with the A1-adenosine receptor
      agonist R(-)-N6-(2-phenylisopropyl) adenosine. The protective effects of both
      ischaemic preconditioning and A1-adenosine receptor activation were prevented by
      6 mg/kg, but not 3 mg/kg, of the K(ATP) channel blocker, glibenclamide, in
      rabbits anaesthetized with pentobarbital, while these effects were prevented by 3
      mg/kg of the blocker in rabbits anaesthetized with ketamine-xylazine. Moreover,
      K(ATP) channel opener, cromakalim, prevented the ischaemia-induced decreases in
      enzymatic activities in rabbits subjected to either type of anaesthesia. Thus,
      although the antagonistic effect of glibenclamide is blunted under pentobarbital,
      compared to ketamine-xylazine anaesthesia, K(ATP) channels contribute to
      preservative actions independent of the type of anaesthesia in the rabbit heart.

PMID- 9160879
TI  - Development and malignant progression of astrocytomas in GFAP-v-src transgenic
      mice.
AB  - We have generated a transgenic mouse model for astrocytoma by expressing the v
      src kinase under control of the glial fibrillary acidic protein (GFAP) gene
      regulatory elements in astrocytes. Abnormal astrogliosis was observed in all
      transgenic animals already at 2 weeks postnatally, frequently followed by the
      development of dysplastic changes. Later, small proliferative foci arose, and
      overt astrocytoma developed in the brain and spinal cord in 14.4% of mice after a
      follow up time of 65 weeks. While early lesions were histologically consistent
      with low-grade astrocytoma, at later stages most tumors were highly mitotic and
      frankly malignant. Vascular endothelial growth factor (VEGF) was expressed by
      tumor cells already at early stages, suggesting induction by v-src, and it was
      most pronounced in pseudopalisading cells surrounding necrotic areas, implying
      additional upregulation by hypoxia. In larger lesions, mitotic activity and
      expression of flk-1, the cognate receptor of VEGF were induced in endothelial
      cells. Therefore, end-stage tumors mimicked the morphological and molecular
      characteristics of human glioblastoma multiforme. Time course and stochastic
      nature of the process indicate that v-src did not suffice for malignant
      transformation, and that astrocytomas were the result of a multistep process
      necessitating co-operation of additional genetic events.

PMID- 9160880
TI  - p53, mutation frequency and apoptosis in the murine small intestine.
AB  - Normal function of the p53 gene is integral to the cellular response to genotoxic
      stress. One prediction arising from this is that p53 deficiency results in an
      increased mutation frequency. However, limited evidence has been produced in
      support of this idea. In order to further investigate the in vivo role of p53 in
      surveillance against mutation, and particularly to address the significance of
      p53-dependent apoptosis, we scored mutation frequency at the Dlb-1 locus within
      cells of the intestinal epithelium of animals which were wild type, heterozygous
      or null for p53 and heterozygous (a/b) at the Dlb-1 locus. Using this assay we
      have shown that loss of a p53-dependent apoptotic pathway is associated with the
      detectable acquisition of mutations, but only at high levels of DNA damage. These
      results question the significance of the immediate 'wave' of p53-dependent
      apoptosis seen in this tissue, particularly as there was a delayed p53
      independent apoptotic pathway. We conclude that loss of p53 function only becomes
      relevant to the in vivo acquisition of mutations and thus tumorigenesis in
      certain circumstances.

PMID- 9160881
TI  - Yeast two-hybrid in vivo association of the Src kinase Lyn with the proto
      oncogene product Cbl but not with the p85 subunit of PI 3-kinase.
AB  - Ligand binding of multi-chain antigen receptors and hematopoietin/cytokine
      receptors results in rapid activation of protein tyrosine kinase (PTK)-dependent
      signalling molecules such as phosphatidylinositol 3-kinase (PI 3-kinase). Co
      precipitation studies have shown that Src-related PTK, such as Lyn, associates
      with the p85 regulatory subunit of PI 3-kinase via SH2 and SH3 domain binding
      with their cognate ligands. More recent studies have shown that the proto
      oncogene product Cbl co-precipitates with p85 following engagement of cytokine
      and antigen receptors. As opposed to in vitro co-precipitation studies, the yeast
      two-hybrid screen reveals in vivo protein-protein interactions. Using the yeast
      two-hybrid screen, we demonstrate an in vivo association of Lyn's SH3 and SH2
      domains with the proline-rich domain of Cbl. Lyn's SH3 and SH2 domains do not
      interact with p85 in the yeast two-hybrid screen, as would be predicted from
      glutathione-S-transferase (GST) fusion protein pull-down or co
      immunoprecipitation studies from whole cell lysates. However, the SH3 domain of
      p85 interacts with the proline-rich domain of Cbl. When yeast were transformed
      with catalytic Lyn, an interaction between p85's SH2 domain and Cbl occurred.
      From the data, we propose the following three step process of PI 3-kinase
      activation: (1) complexes of Lyn-Cbl and Cbl-p85 exist without ligand
      stimulation, (2) upon ligand binding, Lyn becomes active and phosphorylates Cbl,
      and (3) Cbl's tyrosine phosphorylated residue serves as a docking site for the
      SH2 domains of p85 - thereby stabilizing the complex and activating PI 3-kinase.
      The yeast two-hybrid system can be used to dissect the precise mechanisms of in
      vivo protein-protein interactions, including those between phosphotyrosine and
      SH2-containing proteins.

PMID- 9160882
TI  - Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) delays
      and induces escape from senescence in human dermal microvascular endothelial
      cells.
AB  - Like most other normal cells, human endothelial cells possess a limited
      replicative life span, and, after multiple passages in vitro, develop an arrest
      in cell division referred to as replicative senescence. For many cell types
      senescence can be delayed by oncogenes or tumor suppressor genes or prevented
      altogether by malignant transformation; however, once developed, senescence has
      been regarded as irreversible. We now report that a cytokine, vascular
      permeability factor/vascular endothelial growth factor (VPF/VEGF), significantly
      delays senescence in human dermal microvascular endothelial cells (HDMEC).
      Typically, VPF/VEGF-treated HDMEC could be cultured for at least 15-20 more
      population doublings (PD) than control cells. Protection from senescence was
      reversible in that subsequent withdrawal of VPF/VEGF returned cells to the
      senescent phenotype. Expression of several cell cycle-related genes (p21, p16 and
      p27) was significantly reduced in VPF/VEGF-treated cells but p53 expression was
      not significantly altered. Of particular importance, VPF/VEGF was able to rescue
      senescent HDMEC, restoring them to proliferation, to a more normal morphology,
      and to reduced expression of a senescence marker, neutral beta-galactosidase.
      Taken together, VPF/VEGF delayed the onset of senescence and also reversed
      senescence in microvascular endothelial cells without inducing cell
      transformation.

PMID- 9160883
TI  - Identification of Gas6 as a ligand for Mer, a neural cell adhesion molecule
      related receptor tyrosine kinase implicated in cellular transformation.
AB  - Mer/Nyk/Eyk is an orphan receptor tyrosine kinase expressed at high levels in
      monocytes and cells derived from epithelial and reproductive tissues.
      Overexpression of Mer has been associated with lymphoid malignancies. Here we
      identify Gas6, the product of a growth arrest specific gene, as a ligand for Mer.
      Gas6 has previously been shown to activate both Axl and Rse/Tyro3, two other
      receptor tyrosine kinases in the same family as Mer. The apparent relative
      association and dissociation rate constants of Gas6 for soluble Axl, Rse/Tyro3
      and Mer were compared using surface plasmon resonance. Gas6 was shown to induce
      rapid phosphorylation of Mer expressed in several different types of cells. We
      also observed a transient activation of p42 MAP kinase following activation of
      Mer by Gas6. Thus, Gas6 exerts its biological effects through multiple receptor
      tyrosine kinases.

PMID- 9160884
TI  - A complex nine base pair deletion in RET exon 11 common in sporadic medullary
      thyroid carcinoma.
AB  - Genetic alteration of the RET proto-oncogene is associated with multiple
      endocrine neoplasia type 2A and 2B (MEN 2A and MEN 2B), familial medullary
      thyroid carcinoma (FMTC) and Hirschprung's disease. Oncogenically activated RET
      has also been demonstrated in sporadic medullary thyroid tumors, which in some
      cases show somatic missense mutations. We have recently described a complex 9 bp
      deletion in RET exon 11 in a single case of sporadic MTC. In order to determine
      the prevalence of this mutation among sporadic MTC tumors, we have now analysed
      15 cases and five normal controls by PCR-based nonradioactive single-strand
      conformational polymorphism analysis (PCR-SSCP) and fragment size analysis of
      exon 11. DNA was extracted from microdissected tumor tissue or normal cells and
      subjected to nested PCR prior to analysis. A markedly divergent SSCP pattern and
      a PCR fragment 9 bp shorter than normal were demonstrated in 14 of the 15 MTC
      tumors. Sequencing revealed the deletion of nine bases encompassing a key
      cysteine at codon 634, often altered in MEN 2A. Four lymphocyte controls and
      normal thyroid tissue from one patient failed to show the deletion. Several
      factors in the DNA sequence environment immediately surrounding the deletions,
      including an extended inverted repeat, several direct repeats and a so-called
      symmetric element suggest that the deletional events may be non-random.

PMID- 9160885
TI  - YSK1, a novel mammalian protein kinase structurally related to Ste20 and SPS1,
      but is not involved in the known MAPK pathways.
AB  - To clarify the upstream regulatory mechanism of mitogen-activated protein kinase
      (MAPK), we performed the reverse transcriptase-based polymerase chain reaction
      (RT-PCR) with degenerate primers synthesized based on sequences conserved among
      the kinase domains of yeast MAPK kinase kinases (MAPKKKs), Stell, Bck1, and Byr2.
      We isolated several mammalian cDNA fragments that encode kinase subdomains
      sharing significant sequence homology with yeast MAPKKKs. Subsequent screening of
      a HeLa cell cDNA library using one of these cDNA fragments as a probe resulted in
      the isolation of a full-length cDNA that encodes a novel protein kinase. The
      catalytic domain sequence of this gene product is closely related to those of
      budding yeast Sps1 and Ste20 protein kinases. Thus, we call this protein YSK1
      (Yeast Sps1/Ste20-related Kinase 1). The transcript of YSK1 was detected in a
      wide range of tissues and cells. Immunoprecipitated YSK1 shows protein kinase
      activity. Although YSK1 is significantly similar in its kinase domain to kinases
      of the yeast and mammalian MAPK pathways, the overexpression of YSK1 did not lead
      to the activation of the ERK (extracellular signal-regulated kinase) pathway, JNK
      (c-Jun NH2-terminal kinase)/SAPK (stress-activated protein kinase) pathway, or
      p38/Mpk2 pathway. These results suggest that YSK1 may be involved in the
      regulation of a novel intracellular signaling pathway.

PMID- 9160886
TI  - Superimposed histologic and genetic mapping of chromosome 17 alterations in human
      urinary bladder neoplasia.
AB  - Multistep alterations of chromosome 17 in the progression of human urinary
      bladder neoplasia were studied by superimposed histologic and genetic mapping.
      The p53 gene was included in the analysis as a model tumor suppressor gene that
      is frequently involved in urothelial carcinogenesis. The strategy provided a
      systematic approach to the study of multistep genomic alterations that occur as
      neoplasia progresses from precursor intraurothelial conditions to invasive
      cancer. This was accomplished by sampling the entire mucosa of the organ and
      displaying microscopically identified invasive cancer and precursor conditions in
      the form of a histologic map. Subsequent isolation of DNA provided a set of
      samples in which the search for genetic alterations was performed and
      superimposed on the histologic map. This approach disclosed multifocal allelic
      losses of chromosome 17 in the early preinvasive phases of urothelial neoplasia.
      The alterations were predominantly confined to the p12-13, q22-11 and q24-25
      regions. Mutations and allelic losses of the p53 gene were mapped to early
      preinvasive phases of urothelial neoplasia. The data provide detailed analysis of
      chromosome 17 allelic losses that occur in the development and progression of
      urothelial neoplasia and represent the first step for genome-wide modeling of
      multistep human urothelial carcinogenesis.

PMID- 9160888
TI  - The 230 kDa mature form of KDR/Flk-1 (VEGF receptor-2) activates the PLC-gamma
      pathway and partially induces mitotic signals in NIH3T3 fibroblasts.
AB  - KDR/Flk-1 tyrosine kinase, one of the two receptors for Vascular Endothelial
      Growth Factor (VEGF) has been shown to generate the major part of mitotic signals
      in endothelial cells, although the mechanisms are poorly understood. Here we
      examined the processing and signal transduction of KDR/Flk-1. Both in endothelial
      cells and in NIH3T3 cells expressing KDR/Flk-1, an immature form of KDR/Flk-1
      with a molecular mass of about 150 kDa was glycosylated to create a 200 kDa
      intermediate, and after further glycosylation a mature 230 kDa was expressed on
      the cell surface. Only this 230 kDa form was rapidly and transiently
      phosphorylated on tyrosine residues in the presence of VEGF. As a major substrate
      of KDR/Flk-1, PLC-gamma was found to be rapidly tyrosine-phosphorylated and
      associated with KDR/Flk-1 both in endothelial cells and NIH3T3 cells.
      Interestingly, however, a prompt activation of MAP kinase and subsequent strong
      mitotic signaling were generated only in the endothelial cell background.
      Activation of MAP kinase in NIH3T3 cells overexpressing KDR/Flk-1 showed a slower
      response as maximum levels were only attained after 20 min compared to 5 min in
      sinusoidal endothelial cells. These results suggest that the KDR/Flk-1 utilizes
      cell type-specific signal transduction pathway(s) for MAP kinase activation and
      the mitotic response in endothelial cells.

PMID- 9160887
TI  - Characterization of peripheral blood T-lymphocytes transduced with HTLV-I Tax
      mutants with different trans-activating phenotypes.
AB  - Tax1, a transcriptional trans-activator of the Human T-cell leukemia virus type I
      (HTLV-I), induces the expression of many cellular genes through interaction with
      at least three distinct cellular transcription factors; CREB/ATF, NF-kappaB, and
      SRF. This Tax1-induced activation of cellular genes is considered to be a
      critical event in T-cell transformation by HTLV-I. To elucidate the role of each
      Tax1-inducible transcriptional pathway in T-cell transformation, we introduced
      Tax1 mutants with different trans-activating phenotypes into peripheral blood
      lymphocytes (PBL) by retroviral vectors. Analysis of these PBLs revealed that
      activation of the NF-kappaB pathway is sufficient to promote the growth response
      to IL-2. However, for the clonal expansion of CD4+ T-cells, which is a
      characteristic result of HTLV-I infection, activation of the CREB/ATF and SRF
      pathways is also required.

PMID- 9160889
TI  - Cross-family interaction between the bHLHZip USF and bZip Fra1 proteins results
      in down-regulation of AP1 activity.
AB  - Heterodimerization among the basic-leucine zipper (bZIP) proteins or among the
      basic-helix-loop-helix-leucine zipper (bHLHZip) proteins confers a multitude of
      combinational activities to these transcription factors. To further examine the
      function of the bHLHZip protein, USF, we screened for cellular proteins which
      could directly interact with USF using the yeast two-hybrid system. A bZip
      protein, Fra1, was found to efficiently interact with USF. USF specifically
      interacts with Fra1 but not with other closely related family members, c-Fos,
      Fra2, FosB, or with c-Jun. Both the bHLHZip and the N-terminal regions of Fra1
      are required for efficient interaction with USF. In vivo association between USF
      and Fra1 has been demonstrated by co-immunoprecipitation. Expression of exogenous
      USF led to a decrease in AP1-dependent transcription in F9 cells. Co-expression
      of exogenous Fra1 restored the AP1 activity in a dose-dependent manner. These
      data show that USF and Fra1 physically and functionally interact demonstrating
      that cross-talk occurs between factors of distantly related transcription
      families.

PMID- 9160890
TI  - A subclass of tumor-inhibitory monoclonal antibodies to ErbB-2/HER2 blocks
      crosstalk with growth factor receptors.
AB  - ErbB-2 is an orphan receptor that belongs to a family of tyrosine kinase
      receptors for either epidermal growth factor (EGF) or Neu differentiation factor
      (NDF/neuregulin). Because overexpression of the erbB-2 proto-oncogene is
      frequently associated with an aggressive clinical course of certain human
      adenocarcinomas, the encoded protein is an attractive target for immunotherapy.
      Indeed, certain monoclonal antibodies (mAbs) to ErbB-2 effectively inhibit tumor
      growth in animal models and in clinical trials, but the underlying mechanism is
      incompletely understood. To study this question, we generated a large battery of
      mAbs to ErbB-2, that were classified epitopically. Whereas most antibodies
      stimulated tyrosine phosphorylation of ErbB-2, their anti-tumor effect correlated
      with its accelerated endocytic degradation. One group of tumor-inhibitory mAbs
      (Class II mAbs) was elicited by the most antigenic site of ErbB-2, and inhibited
      in trans binding of NDF and EGF to their direct receptors. The inhibitory effect
      was due to acceleration of ligand dissociation, and it resulted in the reduction
      of the ability of ErbB-2 to transactivate the mitogenic signals of NDF and EGF.
      These results identify two potential mechanisms of antibody-induced therapy:
      acceleration of ErbB-2 endocytosis by homodimerization and blocking of
      heterodimerization between ErbB-2 and growth factor receptors.

PMID- 9160891
TI  - The role of p27Kip1 in gamma interferon-mediated growth arrest of mammary
      epithelial cells and related defects in mammary carcinoma cells.
AB  - Interferon gamma (IFNgamma) induces growth arrest in normal human mammary
      epithelial cells by establishing a block during mid-G1 corresponding to the time
      when the retinoblastoma protein (Rb) would normally be inactivated by
      hyperphosphorylation. IFNgamma inhibits the kinase activities of cdk2, cdk4 and
      cdk6 within 24 h of treatment. Protein levels of the cdks and G1 cyclins do not
      change within this time period, although cdk4 levels are significantly reduced by
      48 h. IFNgamma treatment induces p27Kip1 protein levels, presumably by a post
      transcriptional mechanism as no change was observed in the mRNA levels. In
      addition, IFNgamma-induced inhibition of cdk2 and cyclin E-associated kinase
      activities is accompanied by a 4.5-fold or greater increase of p27Kip1 in cdk2
      complexes. p27 may also have a role in the inhibition of cdk4/6 kinase
      activities, as p27 protein associated with these complexes was increase by 55-70%
      after IFNgamma. In mammary carcinoma cell lines which are resistant to growth
      inhibition by IFNgamma, p27 levels are not induced by IFNgamma nor is cdk2 kinase
      activity inhibited, despite high baseline levels of p27 in cdk2 complexes.
      However, exogenous expression of p27 in these cells induces growth arrest. In
      addition, purified p27 protein added to cdk2 complexes immunoprecipitated from
      carcinoma cells is able to inhibit the kinase activity in a dose dependent
      manner. Our results suggest that p27Kip1 has a role in mediating IFNgamma-induced
      terminal growth arrest. Resistance of mammary carcinomas to growth inhibition by
      IFNgamma does not appear to involve resistance of cdk2 complexes to the action of
      p27, but rather an inability to appropriately regulate the balance of cdk2,
      cyclin E and p27 levels.

PMID- 9160892
TI  - Natural 30 base pair and 69 base pair deletion variants of the LMP1 oncogene do
      stimulate NF-kappaB-mediated transcription.
AB  - An increasing number of reports shows a link between the Epstein-Barr virus (EBV)
      and lymphoid neoplasia. The latent membrane protein 1 (LMP1) is likely to play a
      determinant role in this process since this EBV encoded protein has oncogenic
      properties and is usually expressed in EBV-associated lymphoproliferative
      diseases (LPD), except Burkitt's lymphoma. We previously identified in LPD
      patients mutational hot spots and a 30 bp or 69 bp deletion in the LMP1 gene
      region coding for the C-terminal domain. These deletions are located in an area
      shown to be important for the activation of the transcription factor NF-kappaB.
      These findings lead us to test whether these natural deletion variants may have a
      functional effect. We measured the stimulation of their activity using a
      luciferase reporter plasmid containing NF-kappaB responsive elements. We tested
      the NF-kappaB inducing activity of four naturally occurring LMP1 deletion
      variants. Our results show that these deletion variants activate NF-kappaB to the
      same level as the wild-type form, indicating that the crucial residues for NF
      kappaB activation are conserved among the variants isolated and lie within the
      last 32 amino acids of the C-terminal domain of the LMP1 oncogene.

PMID- 9160893
TI  - Astrocytic adhesion molecules are increased in HIV-1-associated cognitive/motor
      complex.
AB  - Half of AIDS dementia cases are associated with HIV-encephalitis or myelin
      pallor. Another half die with no HIV-related neuropathological changes. Previous
      observations suggest that cerebral dysfunction may result from more subtle
      cellular interactions. and that some of them may be mediated by cell adhesion
      molecules. In the present study the expression by astrocytes and endothelial
      cells of intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion
      molecule-1 (VCAM-1) was analysed as a function of the neuropathological
      diagnosis, the density of astrogliosis and of HIV-1 positive cells, and of the
      mental status. Twelve AIDS cases, without focal brain lesion, eight of whom were
      demented, were selected from a prospective study. They were compared with six
      control cases with multiple sclerosis, and with six control patients without
      neurological disease. ICAM-1 and VCAM-1 expression was localized by
      immunofluorescence and confocal microscopy. HIV protein gp41 was detected by
      immunohistochemistry on adjacent sections. Endothelial expression of ICAM-1 and
      VCAM-1 was significantly up-regulated in all AIDS patients. VCAM-1 only was
      related to myelin pallor. The density of VCAM-1 or ICAM-1 positive astrocytes
      increased in demented AIDS patients, independently of the neuropathological
      findings or the density of gp41 positive cells. Expression of cell adhesion
      molecules, together with other secondary mechanisms such as secretion of
      cytokines may play a role in the pathogenesis of white matter lesions leading to
      HIV-1-associated cognitive changes.

PMID- 9160894
TI  - In vivo toxicity of prion protein in murine scrapie: ultrastructural and
      immunogold studies.
AB  - Prion protein (PrP) is a cell surface, host coded, sialoglycoprotein which
      accumulates in excess in scrapie, Creutzfeldt-Jakob disease, bovine spongiform
      encephalopathy and other transmissible spongiform encephalopathies. Infection of
      mice with the 87 V or ME7 scrapie strains results in distinctive and very
      different light microscopical patterns of vacuolation and disease specific PrP
      accumulation. In both of these scrapie strains immunogold electron microscopy was
      used to locate PrP to the plasmalemma of neurons from where it was released into
      the neuropil. Initial PrP accumulation around neurons and in early plaques
      lacking amyloid fibrils was generally not associated with morphological changes
      either of the neuron or dendrite releasing the PrP or in the adjacent neuropil in
      which excess PrP accumulated. However, accumulation of pre-amyloid PrP in some
      brain areas was associated with specific degeneration of dendritic spines and
      axon terminals. Initial PrP aggregation into fibrils was also associated with
      tissue damage with both ME7 and 87 V plaques and diffuse accumulations. Tissue
      damage associated with fibrillogenesis was localized and would not be expected to
      have clinical significance. We conclude that pre-amyloid PrP release and
      accumulation is not invariably toxic, either to the neuron releasing PrP or to
      the neuropil into which it is released. However, axon terminal degeneration and
      dendritic spine loss in some neuroanatomical areas may be indicative of specific
      PrP toxicity and may be the main cause of neurological dysfunction in murine
      scrapie.

PMID- 9160895
TI  - Role of high molecular weight extracellular matrix proteins in glioma cell
      migration.
AB  - Malignant human gliomas are characterized by an uncontrolled cell proliferation
      and infiltrative growth within the brain. Complete surgical removal is difficult
      due to disseminated tumour cells, and the fundamental mechanisms responsible for
      this spread are poorly understood. An extensive tumour cell movement along blood
      vessels is frequently observed and this may be due to specific interactions
      between tumour cell surface receptors and specific extracellular matrix (ECM)
      components present in conjunction with vascular elements. In order to investigate
      the influence of ECM on glioma cell migration, three different human glioma cell
      lines (U-373 MG, A-172 MG and HF-66) were exposed to known ECM components of the
      basement membrane (laminin, fibronectin and collagen type IV). Cell migration
      from multicellular spheroids was studied, using a custom-made medium which was
      prepared by removing the high molecular weight protein fraction (>100 kDa) from
      newborn calf serum by ultrafiltration. To this medium, the specific ECM
      components were added. For two of the cell lines (A-172 MG and U-373 MG), laminin
      was the most potent stimulator of glioma cell migration; the effect of laminin
      exceeded that evoked by ordinary serum-supplemented medium. For the HF-66 cell
      line, fibronectin was the most potent stimulator of migration. Western blot
      analysis showed that the A-172 MG and HF-66 cell lines expressed low amounts of
      laminin compared with U-373 MG, which showed extensive intrinsic synthesis of
      this ligand. U-373 MG was the only cell line that migrated in pure filtered
      medium. The cells stimulated by fibronectin expressed a different morphology from
      those stimulated by laminin suggesting that specific ECM-receptor binding may
      activate different cytoskeletal components within the cells. Furthermore, it was
      shown that there was no difference in the amount of protein synthesis between
      cells grown in filtered medium and in filtered medium supplemented with different
      ECM components. This suggests that ECM-induced cell migration is not dependent on
      a high level of protein synthesis. It is also shown that alpha3 integrin, which
      is a receptor-subunit for laminin, fibronectin and collagen type IV, was highly
      expressed in all cell lines. This study indicates that glioma cells need serum
      proteins with a molecular weight >100 kDa to migrate in vitro, and that laminin
      and fibronectin play an important role in this process.

PMID- 9160896
TI  - Cell-adhesion molecules in human meningiomas: correlation with clinical and
      morphological data.
AB  - Integrins form a family of cell adhesion molecules. CD44 glycoproteins are found
      in a wide variety of isoforms; the most common, CD44s (standard) is widely
      distributed, and functions as an adhesion molecule. In this study, we have
      investigated immunohistochemically the distribution of some VLA integrins
      (alpha2, alpha5 and alpha6 chains of beta1 integrins) and CD44s in 44 meningioma
      specimens and normal arachnoid villi. Meningiomas were of meningothelial (16),
      transitional (13) and fibroblastic (15) subtypes. There were 13 grade I, 19 grade
      II and 12 grade III (27%). Immunoprecipitates were quantified by image analysis
      and correlated with clinical (age, sex, location) and morphological data
      (histological subtypes and grades). VLA alpha5 chain was expressed by normal
      arachnoid villi (mainly cap cells) and by 42 out of 44 meningioma specimens.
      Expression was lower in fibroblastic meningiomas (P=0.02). VLA alpha2 and alpha6
      chains were not observed in normal arachnoid villi. VLA alpha2 was expressed by
      15 meningiomas, VLA alpha6 by 10. Interestingly, meningiomas expressing either
      VLA alpha2 or alpha6 were usually of grade III (P< or =(0.05). CD44s was found on
      various parts of arachnoid villi and in all meningiomas although expression was
      higher in meningothelial and transitional than in fibroblastic (P< or =0.001).
      These results show that VLA alpha5 and CD44s are widely expressed by arachnoid
      villi and meningiomas, in contrast to VLA alpha2 and VLA alpha6. It was noted
      that high grade meningiomas (III) express VLA alpha2 and alpha6 suggesting that
      changes in integrin pattern expression are a feature of these meningiomas.
      Moreover, strong CD44s expression characterizes meningothelial and transitional
      meningiomas. Previous studies have shown that high NCAM expression is a feature
      of fibroblastic meningiomas whereas meningothelial and transitional meningiomas
      expressed mainly E-Cadherin, and that polysialylated NCAM expression was
      restricted to high grade meningiomas. Taken together these features suggest that
      each cell adhesion molecule has a characteristic pattern of expression according
      to meningioma subtype and grade. No correlation was seen between integrins and
      CD44s expression and clinical data.

PMID- 9160897
TI  - A comparative freeze-fracture study of plasma membrane of dystrophic skeletal
      muscles in dy/dy mice with merosin (laminin 2) deficiency and mdx mice with
      dystrophin deficiency.
AB  - The intramembranous particle (IMP), orthogonal array (OA) and orthogonal array
      subunit particle (OASP) densities of skeletal muscle plasma membranes of merosin
      deficient dy/dy mice and their control mice at 7, 14 and 28 days after birth were
      analysed by freeze-fracture electron microscopy. Similar studies were performed
      on dystrophin-deficient mdx mice with mild muscle weakness at 28 days after birth
      for the comparison with those of dy/dy mice with severe muscle weakness at the
      same age. In the pre-clinical stage of dy/dy mice at 14 days after birth, the
      membranes showed a significantly decreased density of OAs (P<0.01 by Wilcoxon
      rank-sum test) as compared with control mice, while those in the clinical stage
      of dy/dy mice at 28 days after birth showed normal IMP density but a marked
      depletion of OA density (P<0.01). Moreover, at 28 days after birth, the reduction
      of OAs in the plasma membranes of dy/dy mice was more marked than that of mdx
      mice (P<0.05 by Wilcoxon rank-sum test). These results provided us with the
      information that the OA density was affected more severely with merosin
      deficiency than with dystrophin deficiency, and again supported our previously
      proposed concept that the clinical severity in muscular dystrophies correlated
      with the OA density.

PMID- 9160898
TI  - Interleukin-1 expression in inflammatory myopathies: evidence of marked
      immunoreactivity in sarcoid granulomas and muscle fibres showing ischaemic and
      regenerative changes.
AB  - The most frequent autoimmune adult inflammatory myopathies are dermatomyositis,
      polymyositis, inclusion body myositis, and sarcoid myopathy. Interleukin-1 (IL-1)
      is a pleiotropic molecule, implicated in the inflammatory process, but also in
      tissue protection and remodelling. We evaluated the immunocytochemical expression
      of [L,-1alpha and beta in frozen muscle biopsy specimens from patients with
      dermatomyositis (15 cases), polymyositis (five cases), inclusion body myositis
      (five cases) and sarcoid myopathy (five cases). Positive immunoreactivities, were
      observed in both inflammatory cells and muscle fibres. Specificity of the
      immunostaining was assessed by Western blot experiments. IL-1 positive
      inflammatory cells were rare in polymyositis and inclusion body myositis,
      moderately abundant in dermatomyositis, and prominent in sarcoid myopathy
      granulomas. In sarcoid myopathy, 24.6 +/- 4.1% inflammatory cells were IL-1alpha
      positive and 45.2 +/- 2.6% were IL-1beta-positive. IL-1 positive muscle fibres
      were mainly observed in dermatomyositis, usually remote from inflammatory
      infiltrates. Positive immunostaining for IL-1 was observed in fibres showing
      ischaemic punched-out vacuoles, that correspond to areas of myosinolysis, in
      atrophic perifascicular fibres, and in fibres located within healing
      microinfarcts. All NCAM-positive regenerating fibres were IL-1 positive. We
      conclude that: (i) IL-1 is expressed in granulomas of sarcoid myopathy, which is
      in keeping with the role ascribed to IL-1 in the formation of granulomas: (ii) IL
      1 is expressed by muscle fibres undergoing ischaemic damage: and (iii) IL-1
      expression by muscle fibres is associated with myofibrillar protein breakdown and
      regeneration.

PMID- 9160899
TI  - DNA-fragmentation and expression of apoptosis-related proteins in experimentally
      denervated and reinnervated rat facial muscle.
AB  - Muscle fibres may undergo apoptotic cell death in several neuromuscular disorders
      such as denervated muscle fibres in spinal muscular atrophies. We investigated
      DNA-fragmentation (in situ by the TUNEL-method) and expression of apoptosis
      associated proteins in experimentally denervated and reinnervated rat facial
      muscle up to 24 weeks after surgery to evaluate the rate and time lapse of
      apoptotic muscle fibre loss. While denervated muscle displayed constantly high
      rates of DNA-fragmentation, denervated and immediately reinnervated muscle showed
      a distinct decrease of primarily elevated DNA-cleavage, finally resembling rates
      of normal controls. Denervated muscle fibres revealed strong immunoreactivity of
      the anti-apoptotic proteins bcl-2 and bcl-xL, and the pro-apoptotic factor bax.
      In reinnervated muscle fibres, only bcl-2 was constantly upregulated while bcl-xL
      and bax diminished after the 7th week. The present findings indicate that
      denervation may prompt muscle fibres to activate an intrinsic 'suicide' programme
      to undergo apoptosis. High levels of bcl-2 after denervation may sustain cell
      survival until reinnervation, e.g. after accidental nerve damage or in
      neurodegenerative disorders. Furthermore, increasing levels of bcl-2 are able to
      neutralize high apoptosis-promoting bax levels. Interventions modifying DNA
      fragmentation and the expression of apoptosis-related proteins may lead to new
      therapeutic concepts in denervating disorders of muscle in the absence of other
      primary therapies.

PMID- 9160900
TI  - Understanding the blood-brain-barrier.

PMID- 9160901
TI  - Color flow mapping and hemodynamics.

PMID- 9160902
TI  - Color flow mapping.
AB  - Color flow mapping systems have become widely used in the short time since their
      development. These systems overlay a pseudo-color velocity map upon the gray
      scale two-dimensional image. Between 4 and 16 pulses are directed to each line-of
      sight, and this requirement reduces the frame rate in comparison with the gray
      scale image. Other limitations of color flow mapping include its ability to
      estimate only the velocity toward or away from the transducer and an increase in
      the variance in comparison with spectral Doppler. Potential artifacts include
      aliased velocities and the detection of flow in hypoechoic or hyperechoic
      nonvascular structures. Clinical applications include cardiology, studies of the
      abdominal and peripheral vasculature, evaluation of organ perfusion and the
      differentiation of tumors. Most current systems use narrowband estimators that
      examine a fixed sample volume and detect a change in phase between two pulses.
      Wideband estimators that can track red blood cells in two or three dimensions are
      under evaluation. Narrowband estimators, including the autocorrelator, the short
      Fourier transform and second order autoregressive filters, are compared with
      wideband estimators including cross-correlation, sum-absolute-difference and the
      wideband maximum likelihood estimator. Because the intensity of blood echoes is
      far smaller than echoes from surrounding tissue, high pass filters have been
      developed that can reject the larger signal from tissue using the return from a
      small number of pulses. Other areas of research include strategies for flow
      estimation with contrast agents, three-dimensional color flow mapping and power
      Doppler flow mapping.

PMID- 9160904
TI  - Ultrasound in ophthalmology.
AB  - The first ocular echogram was published in 1956. Since then, ophthalmic
      ultrasound has developed into a multifaceted diagnostic discipline, the basic
      methods being A-scan and B-scan, Doppler techniques and recently also three
      dimensional approaches. Unique for ophthalmology is the newly invented, highly
      resolving equipment utilising ultrasound frequencies of 50 MHz and higher, so
      called ultrasound biomicroscopy. During this development, the special ophthalmic
      items often kept colleagues from other fields at some distance. With a view to a
      fair balance between specific and more general information, the primary aim of
      the present overview is to provide insight for other medical branches employing
      diagnostic ultrasound. Regarding intraocular morphology, ultrasonic evaluation in
      experienced hands is superior to other imaging methods. As for orbital pathology,
      imaging by CT and MR appears more complete. Ultrasound is valuable, however, in
      particular as part of the initial clinical work-up, and for the follow-up of
      orbital disease. Furthermore, tissue differentiation by way of ultrasound is of
      great value with regard to certain entities.

PMID- 9160903
TI  - Ultrasonic color flow mapping: the visualization of four-dimensional cardiac and
      vascular flow phenomena using two dimensions and "real time".

PMID- 9160905
TI  - Unusual pseudoaneurysms after catheterization: successful treatment by ultrasound
      guided compression.
AB  - Postcatheterization pseudoaneurysms occur mostly in the femoral artery. Two
      patients (both women, aged 67 and 59 years) undergoing percutaneous transluminal
      angioplasty (PTA) at our institution presented pseudoaneurysms in unusual
      locations, one in the brachial and one in the popliteal artery. Because of good
      experiences with ultrasound-guided compression repair (UGCR) in the femoral
      artery, we also successfully performed this noninvasive treatment on the two
      patients. Follow-up at 28 and 12 months, respectively, after the procedure,
      showed no instances of recurrence. As with the excellent results of UGCR in the
      femoral artery, we believe that this new modality is also the treatment of choice
      in iatrogenic pseudoaneurysms of the arm and popliteal arteries.

PMID- 9160906
TI  - Three-dimensional ultrasound assessment of fetal liver volume in normal
      pregnancy: a comparison of reproducibility with two-dimensional ultrasound and a
      search for a volume constant.
AB  - The purposes of this study are to compare the reproducibility of two-dimensional
      ultrasound (2DUS) and three-dimensional ultrasound (3DUS) in the assessment of
      fetal liver volume (LV), and to test whether the fetal LV assessed by the
      traditional method with 2DUS is equal to that with 3DUS in normal pregnancy. If
      significantly different, we then try to calculate a new constant of fetal LV for
      the traditional equation from the LV values obtained with 3DUS. In total, 30
      normal singleton fetuses with gestational ages ranging from 20 to 30 weeks were
      included for the reproducibility test and 55 cases ranging from 20 to 31 weeks
      gestation were enrolled for finding a new volume constant of LV. The results
      showed that 3DUS is superior to 2DUS in the reproducibility test of fetal LV
      assessment. Moreover, the LV assessed with the traditional 2DUS method
      (identified as LV_42) was significantly smaller than that measured with 3DUS (P <
      0.001). If the traditional 2DUS equation is to be used, the multiplying factor in
      the equation for the calculation of LV should be modified to 0.55 (SE = 0.017, N
      = 55). With the new volume constant, the new derived LV with 2DUS (identified as
      LV 55) was not different from that with 3DUS (identified as LV_3D). In
      conclusion, we recommend that 3DUS, instead of 2DUS, should be used for reaching
      an accurate assessment of fetal LV. Otherwise, applying our new volume constant
      may be of help in detecting abnormal fetal liver growth when only 2DUS is
      available.

PMID- 9160907
TI  - Recursive autoregressive spectral maps for ocular pathology detection.
AB  - This article presents a new approach to the problem of obtaining topological maps
      for tissue characterization, based on spectral parameters extracted from radio
      frequency (RF) backscattered ultrasonic signals. The spectral parameter we deal
      with is the power spectral density centroid, since it is an efficient indicator
      of the tissue microstructure characteristics as far as the particle dimensions
      are concerned. The spectral analysis of RF ultrasonic echoes is performed using a
      recursive least-squares scheme with a variable forgetting factor, based on low
      order autoregressive models. The proposed technique is particularly tailored to
      the differentiation of ocular pathologies; moreover, it is capable of tracking
      the spatial high-varying signal characteristics. The proposed approach was tested
      on simulated signals and on a gel suspension of calibrated latex spheres;
      finally, it was applied to signals scattered by in vitro eye specimens, giving
      satisfactory results in terms of frequency resolution and computational
      efficiency. The reduced computational burden allows an on-line implementation of
      the procedure. Topological spectral maps, combined with the conventional B-mode
      display, may offer a complete and integrated diagnostic tool, able to locally
      characterize the investigated tissue region in terms of amplitude and frequency
      shift of the corresponding echoes.

PMID- 9160908
TI  - Influence of data processing on cyclic variation of integrated backscatter and
      wall thickness in stunned porcine myocardium.
AB  - This study was performed to investigate the relationship between the cyclic
      variation of integrated backscatter and myocardial wall thickening in stunned
      myocardium. Different definitions of cyclic variation were evaluated to be able
      to compare with other studies. Ultrasound data were acquired from 10 open-chested
      Yorkshire pigs (25-33 kg) at baseline, during regional ischemia and during 30 min
      of stunning, using a broadband ultrasound transducer (3-7 MHz) sutured directly
      upon the left ventricular myocardial wall. Cyclic variation of integrated
      backscatter and myocardial wall thickening were calculated using three
      definitions obtained from the literature. Independent of the definition, cyclic
      variation of wall thickness and integrated backscatter were blunted during acute
      ischemia and returned transiently to or above baseline during the first minute of
      reperfusion, followed by a gradual decrease to a level under baseline during
      stunning. An early return of the cyclic variation of the integrated backscatter
      was not observed in pigs, independent of the data processing used. The
      relationship between integrated backscatter and wall thickness was maintained.

PMID- 9160909
TI  - Doppler sensors and harnesses for cardiac and peripheral arterial flow
      monitoring.
AB  - The objective of the present work was to design Doppler sensors and harnesses for
      monitoring in real time the cardiac stroke volume and output, the cerebral flow
      volume and resistance and the lower limb arterial flow and resistance changes.
      For the middle cerebral artery investigation we used a 2-MHz transcranial pulsed
      wave (PW) Doppler probe (commercial probe) mounted on a rotula, fixed on the
      horizontal branch of a headset designed like an audio headset. The arch of the
      headset passed over the top of the skull. For the common carotid investigation, a
      4-MHz continuous-wave (CW) or PW flat Doppler probe was inserted in a circular
      silicone support of 5-cm diameter and 0.6-cm thickness. This soft support could
      adapt to the irregular surface of the neck, and the silicone material, which is
      fairly adhesive to the skin, made the system stable. The transducers were
      preoriented at 45 degrees from the support, which provided an acceptable
      orientation of the Doppler beam. The aortic Doppler harness consisted of a 2-MHz
      PW Doppler probe, mounted on a rotula fixed on a plastic rigid support 7 x 1.5
      cm2 in area (parallel to the sternum) whose length could be changed (4-7 cm) to
      localize the rotula and its sensor on the suprasternal area. This flat segment
      was fixed on a rotating platform, part of a solid square plastic support (10 x 10
      cm2) placed on the upper part of the sternum. This system was maintained by
      elastic bands passing around the shoulder and the chest. The femoral Doppler
      harness consisted of a 4-MHz CW or PW flat Doppler probe, inserted in a flat and
      rectangular rigid plastic support 10 x 3 cm2 in area. This rigid support was well
      adapted to the flat surface of the internal part of the thigh, which made the
      system stable. Two elastic bands passed around the thigh and the abdomen, which
      avoided any translation of the support and kept the sensor in contact with the
      skin. The transducers were preoriented at 45 degrees from the support, which
      provided an acceptable orientation of the Doppler beam. The whole Doppler
      monitoring system was successfully tested during orthostatic tests, such as lower
      body negative pressure or tilt table tests performed in pre and post head-down
      tilt experiments and space flights, with the objective of assessing and
      quantifying the cardiac and peripheral arterial hemodynamic changes associated
      with orthostatic intolerance.

PMID- 9160910
TI  - Deconvolution process in measurement of arterial velocity profiles via an
      ultrasonic pulsed Doppler velocimeter for evaluation of the wall shear rate.
AB  - A numerically based simulation of pulsed Doppler ultrasound convolution and
      deconvolution of theoretical hemodynamic velocity profiles yields two major
      conclusions on performing a deconvolution process. First, the most important
      parameter to be accounted for is the size of the sample volume. Second, a
      deconvolution process with an overestimated sample volume size is revealed by
      high-frequency noise on the resulting profile. A deconvolution process is
      presented for in vivo arterial velocity profiles, which has the advantage of
      being systematic and not needing experimental testing for determining the size or
      the shape of the sample volume. It is also independent of the observation angle.
      Finally, an example of an application to in vivo human velocity profiles is
      given. Evaluation of the wall shear rate from the corrected deconvolved profiles
      shows a noticeable improvement with respect to that using the directly convolved
      Doppler profiles.

PMID- 9160911
TI  - An evaluation of the potential and limitations of three-dimensional
      reconstructions from intravascular ultrasound images.
AB  - Three-dimensional (3D) reconstructions of arteries can be produced using two
      dimensional (2D) intravascular ultrasound (IVUS) images. Any artefact that
      affects 2D images has the potential to limit the quality of a 3D reconstruction.
      Using a catheter withdrawal technique, a range of test rigs were used to assess:
      (i) the effect of rotation of the probe orientation; (ii) the ability to
      reconstruct the true path of a tortuous vessel; (iii) the effect of image
      distortion on diameter measurements; (iv) the number of images per unit length
      used to produce a 3D reconstruction; and (v) the quality of the IVUS 3D
      reconstruction of a stent. These investigations show that 3D IVUS imaging is
      prone to artefacts. For 3D IVUS images to be used to quantify the vessel path or
      to make accurate measurements of vessel dimensions, more information about the
      catheter tip position and orientation is required than is currently available
      with the pullback technique.

PMID- 9160912
TI  - Colour velocity flow measurement: in vitro validation and application to human
      carotid arteries.
AB  - Ultrasound measurement of volume blood flow is potentially useful for many
      clinical situations, yet practical implementation and use are restricted by the
      many instrumentation and blood flow limitations that can arise. Colour velocity
      imaging offers a number of theoretical advantages over methods based on duplex
      imaging. We evaluated a colour velocity flow measurement system (CVI-Q, Philips)
      both in a flow phantom and in vivo in the extracranial carotid arteries of normal
      volunteers. Over a range of constant (50-1200 ml/min) and pulsatile (92-366
      ml/min) flows and using both steered and unsteered beams with beam angles of 30
      degrees and 40 degrees, errors usually within 5% were obtained for constant flow
      and within 10% for pulsatile flow. However, with a beam angle of 70 degrees,
      higher errors of 20% were obtained for pulsatile flow. The reproducibility of
      flow measurements made using both anterior and posterior-lateral scanning
      approaches was determined in the common (CCA), internal (ICA) and external
      carotid (ECA) arteries of 18 volunteers. A greater reproducibility was found
      using the posterior-lateral approach (CCA 6.27%; ICA 9.8%), and mean (SD) flow
      values were 376 ml/min in the CCA and 255 ml/min in the ICA. The ratio of (ICA +
      ECA)/CCA flow calculated for each subject individually was mean (SD) 0.95 (0.11).
      Insonation from an anterior approach resulted in lower reproducibility and lower
      flow values. In conclusion, colour flow velocity imaging allows repeatable
      reproducible measurements of CCA and ICA flow, but results are optimal if a
      posterior-lateral scanning approach is used.

PMID- 9160913
TI  - Second harmonic characteristics of the ultrasound contrast agents albunex and
      FSO69.
AB  - Techniques necessary for measurement of the second harmonic of the insonifying
      frequency backscattered from ultrasonic contrast agents are described, and used
      to determine this characteristic for the agents Albunex and FSO69. The results
      confirm theoretical predictions that scattered second harmonic pressure is
      proportional to the square of the incident pressure. Because contrast agents of
      the type investigated improve discrimination of blood echoes against tissue
      echoes by means of the second harmonic of the insonifying frequency, these
      results allow a comparison of the relative merits of Albunex and FSO69 for
      harmonic imaging.

PMID- 9160914
TI  - Quantitation of shock wave cavitation damage in vitro.
AB  - Acoustic cavitation damage was quantitated using aluminum foil targets placed
      within 2-mL polypropylene cryovials. The vials contained various media tested for
      their potential to support cavitation and were exposed to shock waves using an
      unmodified Dornier HM3 lithotripter. Foil damage, expressed in terms of a "damage
      index," was measured from digitized light microscopy images by quantitating the
      spread of gray-scale histograms. Target sensitivity was demonstrated by
      reproducible dose-response curves over the range (1-200 shock waves) commonly
      used for in vitro cell injury studies. Increased shock wave repetition rate
      reduced the damage index. Untreated foils showed a very low damage index (0.001%
      +/- 0.001%), while treated foils submerged in Ringer buffer yielded significant
      damage (2.2% +/- 0.3%, p < 0.001). Degassing the buffer reduced damage to 0.3% +/
      0.1% (p < 0.001). Foils submerged in castor oil showed virtually no damage.
      These results implicate acoustic cavitation in target damage. Targets immersed in
      biological fluids (blood and urine) had significantly less damage than in Ringer.
      The effect of degassing was also evaluated in a red blood cell lysis assay.
      Hemoglobin release in degassed preparations was significantly reduced compared to
      nondegassed controls (p < 0.001) and correlated with reduced foil damage index in
      cell-free vials. These findings characterize a sensitive method to quantitate
      acoustic cavitation and implicate a role for cavitation in shock wave lithotripsy
      induced cell lysis.

PMID- 9160915
TI  - Intraoperative evaluation of small-calibre arterial reconstructions.
AB  - A new hammerhead-shaped, small probe for intraoperative duplex ultrasound was
      devised to evaluate small-calibre arterial reconstructions. This probe was used
      in two patients; one with terminal liver cirrhosis who had a left hepatic lobe
      that had been transplanted from her mother, and a second patient with limb
      threatening ischaemia who had undergone arterial reconstructions. The technique
      was diagnostically useful and contributed to successful clinical outcomes.

PMID- 9160917
TI  - The endoscopic approach for congenital nasolacrimal duct obstruction.
AB  - Probing of the nasolacrimal duct is a common procedure in children with
      congenital stenosis. Although simple probing of the nasolacrimal duct is
      successful in a majority of patients, a number of failures occur. In those
      temporary intubation of the nasolacrimal duct with a silicone drain may solve the
      problem. We performed silicone intubation in 11 infants under nasal endoscopic
      control. By this improved visualization of the inferior meatus, the procedure was
      facilitated. In four children the probe was unable to pierce the nasal mucosa and
      stayed in the submucosal space. An incision of the nasal mucosa was needed before
      the probe could be passed into the nasal lumen. We believe that this situation,
      inability to pierce the nasal mucosa, may explain a number of failures of simple
      probing. It is therefore advisable, especially if initial probing has failed, to
      repeat the procedure under endoscopic control.

PMID- 9160916
TI  - The effect of the H2 antagonist cimetidine on the numbers of CD4+ and CD8+ cells
      in the nasal mucosa of patients with allergic rhinitis.
AB  - This paper reports the effects of the H2 antagonist cimetidine on the number of
      CD4+ and CD8+ cells in nasal mucosa and the IgE level of nasal secretions in
      patients with allergic rhinitis. The results showed the numbers of CD4+ cells
      were greater than the numbers of CD8+ cells in nasal mucosa, both in the patients
      with allergic rhinitis and normal subjects, but the ratio of CD4+:CD8+ cells was
      much higher in the patients with allergic rhinitis. After treatment with
      cimetidine locally for 4 weeks, the numbers of CD4+ cells fell and the numbers of
      CD8+ cells increased in the patients with allergic rhinitis. The high IgE level
      of nasal secretion of the patients with allergic rhinitis was much reduced after
      treatment with cimetidine. The results suggest that there are high numbers of
      CD4+ cells and lower numbers of CD8+ cells in the nasal mucosa and a high level
      of IgE in the nasal secretions of the patients with allergic rhinitis. Treatment
      with cimetidine locally may be of some value to relieve the clinical symptoms of
      allergic rhinitis.

PMID- 9160918
TI  - The effect of immunotherapy on the serum levels of eosinophil cationic protein in
      seasonal allergic rhinitis.
AB  - The role of serum eosinophil cationic protein levels in allergic rhinitis is
      controversial. It is also unclear whether with immunotherapy it is possible to
      reduce these serum levels in allergic diseases. We studied serum eosinophil
      cationic protein levels in patients with cedar-induced allergic rhinitis and
      compared them with non-atopic controls. The second aim of this study was to
      elucidate whether immunotherapy is capable of decreasing the seasonal elevation
      in serum eosinophil cationic protein levels in seasonal allergic rhinitis. The
      serum eosinophil cationic protein levels of the untreated patient group were
      significantly higher than those of the non-atopic controls. The levels in
      patients who received immunotherapy for 2 yr were also significantly higher than
      those of the non-atopic controls. However, the levels were not different between
      the patients undergoing immunotherapy for over 3 yr and the non-atopic controls.
      The serum levels of the 31 patients treated with immunotherapy correlated with
      the duration of immunotherapy. In conclusion, the serum eosinophil cationic
      protein levels are higher in untreated patients with seasonal allergic rhinitis
      and this seasonal activation in circulating eosiohophils decreases gradually
      during immunotherapy, but this inhibitory effect becomes apparent only after a
      number of years of immunotherapy. This prevention of seasonal eosinophil
      activation is one of the mechanisms responsible for the clinical effect of
      immunotherapy.

PMID- 9160919
TI  - Inner ear disorders due to pressure change.
AB  - We reviewed the records of 136 patients who had inner ear disorders including
      hearing loss and vertigo caused by pressure change. We divided them into three
      groups, according to the aetiology: group A, change in atmospheric pressure
      (diving, airplane travel, etc.); group B, rapid change in ear pressure in normal
      atmosphere (nose blowing, heavy lifting, etc.); and group C, blast injury. A flat
      initial audiogram was the most common type in groups A and B. In group C, high
      tone hearing loss was the most common type of audiogram. These results correspond
      to findings previously reported in animal experiments. Exploratory tympanotomy
      was performed more than 12 days after the pressure change in 16 patients.
      Although the vertigo disappeared after surgery, hearing did not improve.

PMID- 9160920
TI  - The growth rate of osteomas of the paranasal sinuses.
AB  - Paranasal sinus osteomas are benign tumours, occasionally known to cause
      complications. They have a tendency to grow slowly, but the growth rate has never
      been evaluated previously. We retrospectively studied 44 patients with paranasal
      sinus osteomas. In 13 out of the 23 patients who underwent at least two sinus
      radiographs at different times some growth was seen. The mean growth rate of
      these 13 osteomas was 1.61 mm/yr, range 0.44 to 6.0 mm/yr. The endoscopic
      technique is a good method for the removal of osteomas and obliteration of the
      frontal sinus does not seem to be necessary. Two patients having osteomas with
      intracranial expansion are described.

PMID- 9160921
TI  - The effect of inflammation on blood vessel area in Rosenthal's canal in the cat
      cochlea.
AB  - The quantitative analysis of spiral ganglion cells is important. It is
      conventionally expressed as a cell density, the number of cells within
      Rosenthal's canal divided by its area. The area of Rosenthal's canal
      conventionally excludes the areas of blood vessels within it. If blood vessels
      proliferate in an inflammatory response then excluding their area may result in
      an under-estimate of cell loss. This study investigates whether blood vessel area
      increases with inflammation. Eighteen implanted and stimulated cat cochleas were
      studied. Using computer aided analysis techniques we measured the areas of
      Rosenthal's canals and its blood vessels. A histologist quantitatively graded the
      inflammation in each cochlea. Blood vessel area increased with the grade of
      inflammation. Multiple regression analysis showed this effect was significant (P
      < 0.01). This increase in blood vessel area may have an effect on density
      measurements made by excluding that area, leading to an under-estimate of
      ganglion cell loss.

PMID- 9160922
TI  - Palliative care in patients with cancer of the head and neck.
AB  - Palliative care is the active total care of patients whose disease is not
      responsive to curative treatment. Patients with end-stage head and neck cancer
      have particular problems because of the impact of the tumour on the airway, the
      upper gastrointestinal tract and the major senses. Patients referred for
      palliative care were identified from the hospice database and the nature,
      incidence and management of their problems, and the role of the hospice in their
      care, was reviewed from in-patient and home care notes and patient-generated
      problem lists. Thirty-two male and six female patients with a median age of 64
      years were identified. Locoregional recurrence was present in 79% of patients.
      Pain, weight loss, feeding difficulties, dysphagia, respiratory symptoms,
      xerostomia, oral thrush and communication difficulties were the major problems.
      The management of each, and of the terminal events encountered in the group, is
      discussed.

PMID- 9160923
TI  - Infectious mononucleosis treated by an antihistamine: a comparison of the
      efficacy of ranitidine (Zantac) vs placebo in the treatment of infectious
      mononucleosis.
AB  - This study investigated whether the course of infectious mononucleosis was
      influenced by medication with ranitidine (Zantac). A double-blind, placebo
      controlled study enrolled 117 patients and either ranitidine 300 mg or placebo
      were given twice daily for 2 wk. Patients were examined on day 5, 10, 15 and 30.
      Efficacy variables included severity and duration of fever, scores of cervical
      lymph node size and tonsil size, eating problems, fatigue, influence on general
      condition, the use of analgesics and blood analyses. Results were analysed in
      91/117 patients. Small differences were found between treatment groups in favour
      of the active drug. However, they were not statistically significant. After 2 wks
      of treatment abnormal 'liver enzymes' (ALAT/ASAT) were found in 13/48 (0.27) of
      the ranitidine group in contrast with 18/36 (0.50) of the placebo group (P =
      0.03). The conclusion is that the course of infectious mononucleosis is little
      influenced by ranitidine treatment for 2 wks. The faster normalization of the
      'liver enzymes' may reflect modulation of the immune system by ranitidine.

PMID- 9160924
TI  - Mode shapes of a damaged and repaired tympanic membrane as analysed by the finite
      element method.
AB  - This work makes use of recent finite element discretization of the human tympanic
      membrane where the known anisotropy of the tympanic membrane is implemented by a
      series of thin beam elements superimposed on thin shell membrane elements. These
      thin beam elements were introduced in order to simulate the fibre structure of
      the tympanic membrane. The onset of tympanosclerosis has been modelled as a
      gradual increase in tympanic membrane density and modulus in the affected area.
      This increased density results in a fall of 55% of the first natural frequency
      for only a 16% area of drum sclerosis. Additionally the amplitude response is
      significantly reduced. Repair of the membrane was simulated by removal of the
      fibre system from the affected area. Under these circumstances the natural
      frequencies virtually return to the healthy state but the mode shapes of
      vibration do not. The repair to the membrane, although not significantly altering
      frequency values, has resulted in a disruption to the normal mode shape patterns
      with consequences in the movements conveyed to the stapes and cochlear fluids.

PMID- 9160925
TI  - A time-dose study of the effect of topical ipratropium bromide on methacholine
      induced rhinorrhoea in patients with perennial non-allergic rhinitis.
AB  - Intranasal application of the anticholinergic drug, ipratropium bromide, is used
      for the treatment of watery rhinorrhoea. We have performed a time-dose study of
      ipratropium bromide in patients with perennial non-allergic rhinitis, using
      rhinorrhoea, induced by nasal methacholine challenge, as a laboratory model. Two
      doses of ipratropium bromide, 40 microg and 80 microg, delivered from a
      pressurized aerosol, were both very effective, reducing the volume of
      methacholine-induced secretion by 85 to 95%. The maximum effect lasted for at
      least 4 h and then slowly diminished. A significant effect was demonstrable for
      12 h with 40 microg and for 18 h with 80 microg ipratropium bromide. These
      results from a laboratory challenge study indicate that the presently used
      frequency of ipratropium bromide, namely four times daily, may not be necessary
      in many patients. Perhaps once in the morning, followed by an as-needed
      medication, will be a better way to use intranasal ipratropium bromide in
      perennial non-allergic rhinitis.

PMID- 9160926
TI  - The relationship between psychosomatic factors and orthostatic dysregulation in
      young men.
AB  - We carried out a questionnaire survey regarding symptoms of orthostatic
      dysregulation and administered the Japanese Edition of the Cornell Medical Index
      Health Questionnaire (JCMI) and the Yatabe-Guilford Personality Test (Y-G test)
      to 151 male medical students (mean age, 24.6 yr). Orthostatic dysregulation was
      identified in 19 (12.5%) of the subjects based on the questionnaire results. The
      percentage classed as types III (possible neurotic) and IV (probable neurotic)
      according to the health questionnaire was 47.3% in the 19 with orthostatic
      dysregulation and 8.9% in the controls (n = 78). The percentage classed as types
      B and E, suggestive of emotional or psychological disturbance according to the
      personality test, was 42.1% in those with orthostatic dysregulation and 8.9% in
      the controls. These differences were significant (P < 0.01). These results
      suggest that psychosomatic factors influence the occurrence of orthostatic
      dysregulation in young men.

PMID- 9160927
TI  - Prevalence and risk factors for perennial allergic rhinitis in Korea: results of
      a nationwide survey.
AB  - A nationwide survey on the prevalence and risk factors for perennial allergic
      rhinitis in Korea was conducted by means of physical examination by
      otolaryngologists from July to October 1991. The total number of subjects
      examined was 9069 and they were drawn from 2899 households in 60 different
      districts throughout the country. The overall prevalence of perennial allergic
      rhinitis was 1.14%. For the evaluation of risk factors for perennial allergic
      rhinitis, a case-control analysis was carried out. The prevalence was influenced
      by age and urban or rural province. Risk factors such as current urban residence,
      urban birth place, overcrowding, higher educational attainment, nasal septal
      deformity and chronic sinusitis with nasal polyposis, indicated an increased risk
      of perennial allergic rhinitis. Other factors such as smoking and personal
      factors showed little influence on prevalence.

PMID- 9160928
TI  - Is the KTP laser effective in tonsillectomy?
AB  - Thirty-eight patients underwent a randomized double-blind trial using the KTP
      laser for tonsillectomy on one tonsil and standard dissection tonsillectomy on
      the other tonsil. Blood loss was less on the laser side. However, pain though
      initially slightly less on the laser side (days 1 and 2 post-operation) was worse
      on the laser side at 2 weeks due to delayed healing of the tonsillar bed. There
      were no primary or reactionary haemorrhages but a 15% incidence of secondary
      haemorrhage on the laser side.

PMID- 9160929
TI  - A national audit of sinus surgery. Results of the Royal College of Surgeons of
      England comparative audit of ENT surgery.
AB  - The results of a national audit of sinus surgery are presented. Forty-six
      consultant ENT surgeons reported on over 2500 sinus procedures. There has been an
      exponential rise in the number of surgeons in England and Wales performing
      functional endoscopic sinus surgery (FESS) in recent years. Sixty-five per cent
      of surgeons in our study used the FESS technique and 81% had formal or other
      training. Outpatient sinus endoscopy and CT scans have become more routine pre
      operative investigations, whilst the use of plain films has waned. There was a
      wide variation in the numbers of FESS procedures performed by individual surgeons
      in the 6-month period (between 5 and 85). The overall complication rate was 0.75%
      for conventional surgery and 1.41% for functional surgery but no major
      complications were recorded. The primary symptom of blockage was most
      successfully treated by both conventional and functional surgery (70% and 84%
      asymptomatic or improved at 6 months). Pain was relieved in 75% of functional
      procedures and 47% of conventional procedures and discharge relieved in 76% of
      FESS procedures and 47% of conventional procedures.

PMID- 9160930
TI  - Is there an evidence base for the practice of ENT surgery?
AB  - In order to assess the strength of the 'evidence base' for the practice of
      otolaryngology a review of recent journal articles was undertaken. A review of
      all articles published during the period 1990-1994 in five major general
      otolaryngology journals was performed. The articles were classified according to
      a standardized scheme from the abstract or, if necessary, the full paper. Papers
      were grouped into observational studies (descriptive or analytical, hypothesis
      testing), controlled trials, randomized controlled trials, audits, non-clinical
      and others. One true meta-analysis was found. Randomized controlled trials
      comprised 0.7%-4% of articles across the journals studied; other controlled
      trials comprised 0.8-2%; and other analytical studies 7.6-21.9%. Very few true
      audits were seen. Descriptive studies were by far the commonest type of paper
      seen. This literature review suggests there is a poor evidence base for our
      specialty if one regards randomized controlled trials as the gold standard.

PMID- 9160931
TI  - Comparison of the effectiveness of uvulopalatopharyngoplasty and laser
      palatoplasty for snoring.
AB  - We present the surgical management of 51 patients with a primary diagnosis of
      snoring. Patients with sleep apnoea syndrome were eliminated from the study. Four
      procedures were used: the classical uvulopalatopharyngoplasty, a limited
      uvulopalatoplasty, laser palatoplasty with tonsillectomy; and laser palatoplasty
      alone. Fifty-one of the 67 patients (76.1%) responded to a telephone
      questionnaire with a mean follow-up period of 18.2 months, 78.4% of patients
      reported improved or absent snoring. There was almost equal patient satisfaction
      between the conventional technique and the laser technique. The improvement in
      snoring was not influenced by the type of operation performed.

PMID- 9160932
TI  - Histology of the perforated tympanic membrane and its muco-epithelial junction.
AB  - A histological study was performed on total human tympanic membranes with a
      central perforation. The specimens originated from 30 consecutive and unselected
      operations in which a total myringectomy was performed prior to reconstruction by
      means of a tympanic allograft. Beside excessive thickening of the tympanic
      membrane in 73%, all membranes showed other histological abnormalities:
      inflammation (97%), excessive fibrosis (97%), tympanosclerosis (80%),
      hyperkeratosis (83%), rete riges (43%) and epithelial inclusions (6%).
      Histological localisation of the muco-epithelial junction showed a medial
      position in 30%, with extensive middle ear invasion by squamous epithelium in 7%.
      The surgeon performing myringoplasty should keep these findings in mind and he
      should closely examine the medial side of the perforated tympanic membrane in
      order to remove any ingrowing epithelium that otherwise would be trapped.

PMID- 9160933
TI  - Polypoidal rhinosinusitis in cystic fibrosis: a clinical and histopathological
      study.
AB  - The eosinophil may play a key role in the pathogenesis of nasal polyposis. Polyps
      in cystic fibrosis, however, have been described as neutrophilic. We compared the
      cell counts in polyps from 44 patients with cystic fibrosis to polyps from 50
      patients without cystic fibrosis. The clinical profile, CT-scan and time to polyp
      recurrence were also compared with the cell counts in the patients with cystic
      fibrosis. No significant difference was detected in the number of patients with
      eosinophils (P > 0.25). Significantly more patients in the group with cystic
      fibrosis had polyp neutrophils (P < 0.01). Polyps from patients without cystic
      fibrosis contained more eosinophils (P < 0.001) whilst polyps from patients with
      cystic fibrosis contained more neutrophils (P = 0.001) and plasma cells (P =
      0.038). Significant correlation was found between the neutrophil count and the CT
      score (P = 0.025) and between the recurrence time of polyps and the macrophage
      count (P = 0.01). Eosinophils are present in varying degrees in polyps from
      patients with and without cystic fibrosis and to classify polyps as eosinophilic
      or neutrophilic may be a false distinction.

PMID- 9160934
TI  - Assessment of adenoid size in children by fibreoptic examination.
AB  - In order to investigate the relationship between the size of the adenoid and
      upper respiratory symptoms in children, fibreoptic examination of the nasal
      cavity and nasopharynx was performed in 817 children. The size of the adenoid was
      classified into three categories according to the distance between the vomer and
      the adenoid tissue. There was a significant relation between the size of the
      adenoid and the complaints of nasal obstruction (P < 0.001) and of snoring (P <
      0.001), but not with the presence of purulent sinusitis. In the whole population,
      the size of the adenoid correlated well with the results of tympanometry (P <
      0.001), but this does not hold in all age groups. This study has confirmed
      adenoid hypertrophy as a common aetiological factor in children with the
      complaints of nasal obstruction and snoring. The enlargement of the adenoid only
      partially explains the occurrence of otitis media with effusion. The introduction
      of the flexible fibrescope in the examination of the nasal cavity and nasopharynx
      in children is of great clinical value, especially in the selection of children
      for adenoidectomy. It is a minor invasive examination well tolerated by most
      children, giving more information than a lateral skull radiograph and avoiding
      unnecessary radiation.

PMID- 9160935
TI  - Interlocking intramedullary nailing with and without reaming for the treatment of
      closed fractures of the tibial shaft. A prospective, randomized study.
AB  - One hundred and fifty-two patients who had 154 closed fractures of the shaft of
      the tibia were prospectively randomized to management with interlocking
      intramedullary nailing either with or without reaming. Thirteen patients who had
      been randomized to treatment without reaming were switched to the group that had
      reaming because of technical reasons; these patients were excluded from the
      analysis of the results. An additional five patients were lost to follow-up.
      Thus, seventy-two patients (seventy-three fractures) who had been managed with
      nailing with reaming and sixty-three patients (sixty-three fractures) who had
      been managed with nailing without reaming were available for follow-up at an
      average of twelve months (range, three to thirty-three months) postoperatively.
      The two groups were similar with regard to demographics and the configurations of
      the fractures. The average total duration of the procedures performed without
      reaming was eleven minutes shorter than that of the procedures done with reaming
      (p = 0.0013). The duration of fluoroscopy was not significantly different between
      the two groups (p = 0.35, Mann-Whitney test). The average estimated blood loss
      was identical for the two groups. Seventy fractures (96 per cent) that were
      treated with nailing with reaming and fifty-six (89 per cent) that were treated
      with nailing without reaming united without the need for an additional operation
      (p = 0.19). Because of the small sample size, the study has insufficient power
      (34.7 per cent) to detect this difference if it is real. There was only one deep
      infection, which developed after nailing without reaming. The nail fractured
      after one procedure with reaming. A screw fractured after two procedures with
      reaming and after ten without reaming (p = 0.012); multiple screws fractured
      after three procedures in the latter group. Malunion occurred after three nailing
      procedures with reaming and after two without reaming. Four malunions were of
      very proximal fractures and one was of a very distal fracture. Seventeen screws
      and twenty-four nails were removed after nailing with reaming, and twenty screws
      and nineteen nails were removed after nailing without reaming; neither of these
      prevalences was significantly different between the two groups (p = 0.27 and
      0.89; chi-square test). We concluded that there are no major advantages to
      nailing without reaming as compared with nailing with reaming for the treatment
      of closed fractures of the shaft of the tibia. There was a higher prevalence of
      delayed union and breakage of screws after nailing without reaming.

PMID- 9160936
TI  - Effect of the duration of room-temperature ischemia on function of the vascular
      endothelium: the role of adrenomedullin in reperfusion injury.
AB  - The function of the vascular endothelium after storage at room temperature (24
      degrees Celsius) for four, eight, and twenty-four hours was investigated with use
      of an ex vivo canine tibial perfusion model. Function was assessed in terms of
      changes in perfusion pressure and changes in the concentration of endothelin-1 in
      the venous effluent of the perfused tibiae. Endothelin-1 is a potent
      vasoconstrictor that is produced in low concentrations by normal endothelial
      cells and in increased concentrations by injured vascular endothelial cells. The
      mean perfusion pressures at flow rates of 1.0 and 1.5 milliliters per minute were
      significantly higher in the tibiae that had been stored for eight hours than in
      the tibiae that had been stored for four hours (p < 0.05), and they were
      significantly higher in the tibiae that had been stored for twenty-four hours
      than in the tibiae that had been stored for four or eight hours (p < 0.05). The
      increase in perfusion pressure with increasing duration of storage was associated
      with an increase in production of endothelin-1. The production of endothelin-1 in
      the tibiae that had been stored for eight hours (10.6 +/- 0.46 picograms per
      milliliter) was approximately ten times greater than that in the tibiae that had
      been stored for four hours (1.1 +/- 0.29 picograms per milliliter). The tibiae
      that had been stored for twenty-four hours had 19.1 +/- 1.5 picograms of
      endothelin-1 per milliliter, nearly twice that produced in the tibiae that had
      been stored for eight hours. Injection of acetylcholine demonstrated muscarinic
      receptor-mediated vasodilation in the tibiae that had been stored for four hours.
      In contrast, the tibiae that had been stored for eight and twenty-four hours had
      no evidence of acetylcholine-induced vasodilation of baseline perfusion vascular
      smooth-muscle tone. However, there was some preservation of endothelium-dependent
      vascular smooth-muscle relaxation in the tibiae that had been stored for eight
      and twenty-four hours, as norepinephrine-induced vascular smooth-muscle
      contraction was significantly greater in the presence of N(G)-monomethyl-L
      arginine acetate (p < 0.05). Moreover, in the second phase of the study, a bolus
      injection of calcium ionophore A23187 in tibiae that had been stored for twenty
      four hours relaxed vascular smooth muscle. Adrenomedullin, a novel peptide with
      known vasodilator properties, relaxed vascular smooth muscle in all three groups
      and also attenuated the pressor response to norepinephrine. In conclusion, the
      function of the vascular endothelium was impaired after storage at room
      temperature for four hours. However, the vascular endothelium in the tibiae that
      had been stored for twenty-four hours maintained some function with regard to the
      production of nitric oxide. The effect of adrenomedullin as a potent vasodilator
      was observed in the tibiae that had been stored for four, eight, and twenty-four
      hours.

PMID- 9160937
TI  - Severin classification system for evaluation of the results of operative
      treatment of congenital dislocation of the hip. A study of intraobserver and
      interobserver reliability.
AB  - The Severin classification system frequently is used to evaluate the radiographic
      results of operations performed for the treatment of congenital dislocation of
      the hip. However, the reliability of this classification scheme has not been
      established, to our knowledge. Ideally, a classification system should be
      validated before it is used to promote therapeutic guidelines or to compare
      results of treatment; the purpose of the present study was to establish the
      intraobserver and interobserver reliability of the Severin classification system.
      Four blinded raters and the operating surgeon independently used the Severin
      system to evaluate the most recent radiographs of thirty-seven children (fifty
      six hips) who had been managed, an average of nine years previously, with a
      medial open reduction for congenital dislocation of the hip. Three of the raters
      evaluated the same radiographs again under similar testing circumstances eight
      weeks later. Ten paired interobserver and three intraobserver comparisons then
      were analyzed with use of the Cohen kappa coefficient (kappa). The average kappa
      coefficient for the six pairwise comparisons between the four blinded raters was
      0.15 (range, -0.05 to 0.42) when all Severin classes were analyzed independently.
      The average kappa coefficient for the four pairwise comparisons between the
      blinded raters and the operating surgeon was even lower (0.02). The kappa
      coefficients for the three intraobserver comparisons were 0.20, 0.38, and 0.44
      (average, 0.34). Kappa analysis demonstrated variable and low levels of agreement
      when the Severin system was used to rate the results of operations performed for
      the treatment of congenital dislocation of the hip. We believe that the
      unadjusted kappa coefficient should indicate excellent agreement (kappa > 0.75)
      for all comparisons if this system is to be used for the evaluation of clinical
      results. The unacceptably low levels of intraobserver and interobserver
      reliability call into question the clinical conclusions of reports in which the
      Severin system has been used as the basis of proof.

PMID- 9160938
TI  - A meta-analysis of the efficacy of non-operative treatments for idiopathic
      scoliosis.
AB  - With use of data culled from twenty studies, members of the Prevalence and
      Natural History Committee of the Scoliosis Research Society conducted a meta
      analysis of 1910 patients who had been managed with bracing (1459 patients),
      lateral electrical surface stimulation (322 patients), or observation (129
      patients) because of idiopathic scoliosis. Three variables - the type of
      treatment, the level of maturity, and the criterion for failure - were analyzed
      to determine which had the greatest impact on the outcome. We also examined the
      effect of the type of brace that was used and the duration of bracing on the
      success of treatment. The number of failures of treatment in each study was
      determined by calculating the total number of patients who had unacceptable
      progression of the curve (as defined in the study), who could not comply with or
      tolerate treatment, or who had an operation. The percentage of patients who
      completed a given course of treatment without failure, adjusted for the sample
      sizes of the studies in which that treatment was used, yielded the weighted mean
      proportion of success for that treatment. The weighted mean proportion of success
      was 0.39 for lateral electrical surface stimulation, 0.49 for observation only,
      0.60 for bracing for eight hours per day, 0.62 for bracing for sixteen hours per
      day, and 0.93 for bracing for twenty-three hours per day. The twenty-three-hour
      regimens were significantly more successful than any other treatment (p <
      0.0001). The difference between the eight and sixteen-hour regimens was not
      significant, with the numbers available. Although lateral electrical surface
      stimulation was associated with a lower weighted mean proportion of success than
      observation only, the difference was not significant, with the numbers available.
      This meta-analysis demonstrates the effectiveness of bracing for the treatment of
      idiopathic scoliosis. The weighted mean proportion of success for the six types
      of braces included in this review was 0.92, with the highest proportion (0.99)
      achieved with the Milwaukee brace. We found that use of the Milwaukee brace or
      another thoracolumbosacral orthosis for twenty-three hours per day effectively
      halted progression of the curve. Bracing for eight or sixteen hours per day was
      found to be significantly less effective than bracing for twenty-three hours per
      day (p < 0.0001).

PMID- 9160939
TI  - Rupture of the posterior tibial tendon. Evaluation of injury of the spring
      ligament and clinical assessment of tendon transfer and ligament repair.
AB  - Eighteen of twenty-two patients who were having a tendon transfer to treat
      rupture of the posterior tibial tendon had evidence of injury to the spring
      ligament. The injury consisted of a longitudinal tear in the ligament in seven
      patients, a lax ligament without a gross tear in seven, and a complete rupture of
      the ligament in four. The ruptured posterior tibial tendon was treated with
      transfer of the flexor digitorum longus in twenty of the twenty-two patients. A
      variety of methods were used to repair the ligament. It is essential to determine
      the status of the spring ligament when patients are managed for rupture of the
      posterior tibial tendon. Patients who have a torn or lax spring ligament in
      addition to the ruptured posterior tibial tendon may have more severe
      abnormalities of the hindfoot than those who have only a ruptured tendon.

PMID- 9160940
TI  - Measurement of polyethylene wear in acetabular components inserted with and
      without cement. A randomized trial.
AB  - We measured the three-dimensional wear of polyethylene after total hip
      arthroplasty with a titanium metal-backed Mallory-Head prosthesis that was
      inserted with cement in sixty-nine patients (sixty-nine hips) and with a press
      fit titanium metal-backed Mallory-Head prosthesis that was inserted without
      cement in seventy patients (seventy hips). A modular titanium femoral head was
      used in all of the hips. The patients in the present study were part of a larger
      double-blind randomized trial comparing the result of total hip arthroplasty
      performed with cement with that of the same procedure performed without cement in
      250 patients. The criterion for inclusion in the study of polyethylene wear was a
      minimum duration of follow-up of four years, which was met by 148 patients. As
      adequate radiographs for digitization were not available for nine patients, 139
      patients were included in the present study. The age of the patient, the
      postoperative Harris hip score, the diameter of the femoral head, the thickness
      of the liner in the polar region of the acetabular component, and the duration of
      follow-up were similar for the two groups. The mean rate of volumetric wear of
      the polyethylene was significantly greater in the prostheses that had been
      inserted without cement than in those that had been inserted with cement (155.1
      cubic millimeters per year compared with 98.5 cubic millimeters per year; p =
      0.000008). Thirty-four (49 per cent) of the seventy hips in which the prosthesis
      had been inserted without cement had evidence of osteolysis on radiographs,
      compared with twelve (17 per cent) of the sixty-nine hips in the other group (p =
      0.0002). Osteolysis was associated with an increased rate of polyethylene wear
      only in the hips in which the prosthesis had been inserted without cement.

PMID- 9160941
TI  - Digital edge-detection measurement of polyethylene wear after total hip
      arthroplasty.
AB  - A novel digital edge-detection computer technique was developed to measure
      polyethylene wear after total hip arthroplasty. The new method objectively infers
      the margins of the component by evaluating gradients of gray-scale intensity on
      digitized images of the radiographs. Compared with previous methods for
      measurement of wear, digital edge detection substantially reduces observer
      subjectivity. The technique was validated directly by measuring wear artificially
      produced by spherical-front milling of polyethylene liners in a benchtop series.
      Under such conditions, digital edge detection proved 6.4 times more accurate and
      7.1 times more reproducible than manual measurement with conventional circular
      templates. In addition, clinical application of the new digital imaging technique
      was illustrated in a series of forty-three patients in whom a metal-backed
      acetabular cup had been inserted with cement. A random-coefficients prediction
      algorithm was invoked to estimate long-term wear (mean late rate of wear for the
      cohort, 0.087 millimeter per year at a mean of 118 months after the operation) on
      the basis of measurements of short-term wear (mean early rate of wear for the
      cohort, 0.154 millimeter per year at a mean of twenty-four months).

PMID- 9160942
TI  - The fate of well fixed cemented femoral components left in place at the time of
      revision of the acetabular component.
AB  - The results were reviewed for thirty-seven hips (thirty-five patients) in which a
      well fixed femoral component that originally had been implanted with use of a so
      called first-generation cementing technique was subsequently left in place at the
      time of revision of the acetabular component without cement. The purpose of the
      study was to determine the rate of survival of the femoral component and the
      complications associated with revision of one side of the joint. The femoral
      components had been in situ for a mean duration of 102 months (range, twelve to
      216 months) at the time of the revision of the acetabular component. At the time
      of follow-up after the revision of the acetabular component, one patient (one
      femoral component; 3 per cent) had died, twenty-seven femoral components (73 per
      cent) were in place and radiographically stable, one femoral component had been
      removed because of infection, six (16 per cent) had been revised because of
      aseptic loosening, and two (5 per cent) were definitely loose according to
      radiographic criteria. Excluding the failures and death, the mean duration of
      follow-up was sixty-five months (range, forty-eight to 121 months). The predicted
      survival of the femoral component after the revision of the acetabular component
      was 88 per cent (95 per cent confidence interval, 82 to 94 per cent) at forty
      eight months and 78 per cent (95 per cent confidence interval, 67 to 89 per cent)
      at eighty-eight months. Dislocation occurred in three hips (8 per cent), and a
      trochanteric non-union occurred in five (14 per cent). The mean rate of linear
      polyethylene wear did not differ significantly (0.13 as compared with 0.12
      millimeter per year; p = 0.74) from that for a comparable group of forty-nine
      hips that had had a revision of the femoral component without cement and had been
      followed for a similar duration. The data support the decision to retain a well
      fixed femoral component that has been implanted with a so-called first-generation
      cementing technique when the acetabular component subsequently needs a revision.
      The survival of the femoral component and the risk of associated complications do
      not appear to be appreciably altered by revision of the other side of the joint.

PMID- 9160943
TI  - In vivo skeletal responses to porous-surfaced implants subjected to small induced
      motions.
AB  - Cylindrical porous-coated implants were placed in the distal femoral metaphyses
      of twenty dogs and were subjected to zero, twenty, forty, or 150 micrometers of
      oscillatory motion for eight hours each day for six weeks with use of a specially
      designed loading apparatus. The in vivo skeletal responses to the different
      magnitudes of relative motion were evaluated. Histological analysis demonstrated
      growth of bone into the porous coatings of all of the implants, including those
      that had been subjected to 150 micrometers of motion. However, the ingrown bone
      was in continuity with the surrounding bone only in the groups of implants that
      had not been subjected to motion or that had been subjected to twenty micrometers
      of motion; in contrast, the implants that had been subjected to forty micrometers
      of motion were surrounded in part by trabecular bone but also in part by
      fibrocartilage and fibrous tissue, and those that had been subjected to 150
      micrometers of motion were surrounded by dense fibrous tissue. Trabecular
      microfractures were identified around three of the five implants that had been
      subjected to forty micrometers of motion and around four of the five that had
      been subjected to 150 micrometers of motion, suggesting that the ingrown bone had
      failed at the interface because of the large movements. The architecture of the
      surrounding trabecular bone also was altered by the micromotion of the implant.
      The implants that had stable ingrowth of bone were surrounded by a zone of
      trabecular atrophy, whereas those that had unstable ingrowth of bone were
      surrounded by a zone of trabecular hypertrophy. The trabeculae surrounding the
      fibrocartilage or fibrous tissue that had formed around the implants that had
      been subjected to forty or 150 micrometers of motion had been organized into a
      shell of dense bone tangential to the implant (that is, a neocortex outside the
      non-osseous tissue).

PMID- 9160944
TI  - Massive, irreparable tears of the rotator cuff. Results of operative debridement
      and subacromial decompression.
AB  - Thirty-three consecutive patients in whom an irreparable tear of the rotator cuff
      had been treated with operative debridement and subacromial decompression were
      evaluated both preoperatively and postoperatively with regard to pain, ability to
      perform activities of daily living, range of motion, strength, and satisfaction.
      The assessments were performed with the Shoulder Score Index of the American
      Shoulder and Elbow Surgeons and the scoring systems of the University of
      California at Los Angeles and Constant and Murley. At the time of follow-up,
      twenty-six patients thought that the condition of the shoulder was improved;
      three, that it was unchanged; and four, that it was worse after the operation.
      There was a significant decrease in pain (p = 0.001) and significant increases in
      the range of motion (p = 0.038) and the ability to perform activities of daily
      living (p = 0.016). However, these improvements were inferior to those in
      reported series in which torn rotator cuffs had been repaired. Strength with
      elevation was decreased after the operations in the present series (p = 0.0007).

PMID- 9160945
TI  - Operative treatment of irreparable rupture of the subscapularis.
AB  - Between 1980 and 1994, 221 shoulders with recurrent anterior glenohumeral
      subluxation or dislocation were reconstructed at our institution. At the time of
      the operation, thirteen shoulders were found to have an irreparable injury of the
      subscapularis muscle, which we believed to be a contributing factor to the
      ongoing instability. All but three of the thirteen patients had had two to six
      previous reconstructions. Operative treatment of the irreparable rupture included
      a dynamic muscle transfer using the pectoralis major in seven shoulders, the
      pectoralis minor in five, and both of these muscles in one. According to a
      modification of the grading system of Neer and Foster, the result was
      satisfactory for ten shoulders and unsatisfactory for three at a mean of five
      years after the operation. All shoulders with a satisfactory result demonstrated
      active contraction of the transferred pectoralis muscle and diminished anterior
      glenohumeral translation. On the basis of our analysis, we concluded that
      transfer of the pectoralis muscle is effective for reconstruction of the shoulder
      in patients who have loss of the subscapularis muscle.

PMID- 9160946
TI  - Non-operative treatment of subacromial impingement syndrome.
AB  - We performed a retrospective study of 616 patients (636 shoulders) who had
      subacromial impingement syndrome to assess the results of non-operative
      treatment. The diagnosis was made on the basis of a positive impingement sign and
      the absence of other abnormalities of the shoulder, such as full-thickness tears
      of the rotator cuff, osteoarthrosis of the acromioclavicular joint, instability
      of the glenohumeral joint, or adhesive capsulitis. All patients were managed with
      anti-inflammatory medication and a specific, supervised physical-therapy regimen
      consisting of isotonic exercises for strengthening of the rotator cuff. The
      average duration of follow-up was twenty-seven months (range, six to eighty-one
      months). Over-all, 413 patients (67 per cent) had a satisfactory result. One
      hundred and seventy-two patients (28 per cent) had no improvement and went on to
      have an arthroscopic subacromial decompression. Thirty-one patients (5 per cent)
      had an unsatisfactory result but declined additional treatment. Seventy-four (18
      per cent) of the 413 patients who had a successful result had a recurrence of the
      symptoms during the follow-up period; the symptoms resolved with rest or after
      resumption of the exercise program. The patients were stratified according to
      age, the duration of symptoms, and acromial morphology. Patients who were twenty
      years old or less and those who were forty-one to sixty years old fared better
      than those who were twenty-one to forty years old. Patients who were more than
      sixty years old had the poorest results. Sixty-seven (78 per cent) of the eighty
      six patients in whom the symptoms had been present for less than four weeks had a
      satisfactory result, compared with 144 (63 per cent) of the 228 who had had the
      symptoms for one to six months and with 202 (67 per cent) of the 302 who had had
      the symptoms for more than six months. Thirty-two (91 per cent) of the thirty
      five patients who had a type-I acromion had a successful result, compared with
      173 (68 per cent) of the 256 who had a type-II acromion and with 208 (64 per
      cent) of the 325 who had a type-III acromion. Shoulder dominance, gender, and
      concomitant tenderness of the acromioclavicular joint did not affect the result
      significantly (p = 0.084, 0.555, and 0.365, respectively).

PMID- 9160947
TI  - A self-administered questionnaire for assessment of symptoms and function of the
      shoulder.
AB  - A self-administered questionnaire was designed to assess the severity of symptoms
      related to and the functional status of the shoulder. It includes domains of
      global assessment, pain, daily activities, recreational and athletic activities,
      work, satisfaction, and areas for improvement. Each domain is graded separately
      and is weighted to arrive at the total score. The over-all scale and each domain
      were prospectively tested for validity, reliability, and responsiveness to
      clinical change. One hundred patients who were seen for evaluation of the
      shoulder were enrolled in the study. The validity of the scale was demonstrated
      by moderate-to-high correlation of the domains and individual questions of the
      Shoulder Rating Questionnaire with those of the Arthritis Impact Measurement
      Scales 2. Validity was supported further by significant correlation of the scores
      in each domain with the level of satisfaction in that domain and by significantly
      lower scores in domains that patients selected as areas important for
      improvement. The over-all scale and each domain were internally consistent
      (Cronbach alpha, 0.71 to 0.90). Reproducibility was evaluated by repeated
      administration of the questionnaire after a mean of three days to forty patients
      whose condition was clinically stable. Reproducibility of the over-all
      questionnaire and individual domains was excellent (Spearman-Brown index, 0.94 to
      0.98). Individual questions were reproducible, with a weighted kappa value of
      more than 0.7 for each. Responsiveness was evaluated by comparison of the
      preoperative and postoperative scores of thirty patients who had a satisfactory
      result one year after an operation on the shoulder. The over-all Shoulder Rating
      Questionnaire and each domain were responsive to clinical change as demonstrated
      by favorable standardized response means (range, 1.1 to 1.9) and indices of
      responsiveness (range, 1.1 to 2.0). Similar analysis performed for individual
      diagnostic groups supported the validity, reliability, and responsiveness of the
      questionnaire in each group. The self-administered shoulder questionnaire was
      found to be valid, reliable, and responsive to clinical change. These qualities
      should make it a useful instrument for the prospective assessment of the outcome
      of treatment of disorders related to the shoulder.

PMID- 9160948
TI  - Early excision of heterotopic ossification about the elbow followed by radiation
      therapy.
AB  - We reviewed the results, in eight patients, of excision of heterotopic
      ossification about the elbow performed three to ten months (average, seven
      months) after the initial injury and followed by radiation therapy to prevent
      recurrence. The etiology of the heterotopic ossification included a neurological
      (head or spinal cord) injury in five patients and a local injury (fracture or
      fracture-dislocation) of the elbow in three patients. The average preoperative
      arc of motion of the three joints that were capable of motion was 12 degrees (5,
      10, and 20 degrees); the remaining five joints were fixed in an average of 56
      degrees (range, 10 to 90 degrees) of flexion. All of the patients received a
      total dose of radiation of 1000 centigray, divided into five fractions. The
      radiation therapy was instituted on the first postoperative day, and at least
      three of the remaining four treatments were administered on consecutive days.
      Radiation therapy was not performed on the weekend, so the five fractions were
      administered over the course of seven days. At an average of forty-six months
      (range, twenty-five to seventy-two months), the arc of motion averaged 103
      degrees, which compared favorably with the 121-degree arc of motion that had been
      attained intraoperatively. Two patients who had residual motor deficits in the
      involved extremity had an arc of motion of 50 and 70 degrees at the latest follow
      up evaluation; those who had normal motor function fared considerably better,
      averaging 118 degrees of motion. There was no substantial recurrence of
      ossification either radiographically or that limited motion, and no complications
      attributable to the radiation therapy were noted. On the basis of this
      experience, it seems that the generally recommended twelve to eighteen-month
      delay between injury and excision, to allow for maturation of heterotopic bone
      and thus to lessen the likelihood of recurrence, may be eliminated. Additional
      studies are needed to define the relative risk of recurrence in the various
      clinical settings in which heterotopic ossification is seen and to determine
      whether radiation therapy is necessary to prevent recurrence after early excision
      in each of these instances.

PMID- 9160949
TI  - Procurement of bone graft from the iliac crest. An operative approach with
      decreased morbidity.
AB  - We compared the donor site morbidity in fifty-seven consecutive patients in whom
      a bone graft had been procured from the iliac crest through an incision parallel
      to the superior cluneal nerves and perpendicular to the posterior iliac crest
      (the study group) with that in fifty-three consecutive patients in whom the graft
      had been procured through an oblique incision parallel to the posterior iliac
      crest (the control group). Numbness, tenderness, and pain at the donor site one
      and six months postoperatively were assessed by means of an interview with the
      patient and a review of the records. The prevalence of symptoms in the control
      group was greater than that in the study group. At one month, thirty-nine
      patients (74 per cent) in the control group had numbness, compared with twenty
      five (44 per cent) in the study group (p = 0.001). At six months, thirty-one
      patients (58 per cent) in the control group had numbness, compared with fourteen
      (25 per cent) in the study group (p = 0.0002). Thirty-six patients (68 per cent)
      in the control group and twenty-four (42 per cent) in the study group had
      tenderness over the incision at one month (p = 0.005), and twenty-seven (51 per
      cent) and eleven (19 per cent), respectively, had tenderness at six months (p =
      0.0003). Forty patients (75 per cent) in the control group and forty-six patients
      (81 per cent) in the study group had deep pain in the region of the iliac crest
      at one month, compared with thirty-two (60 per cent) and thirty-one (54 per
      cent), respectively, at six months. The mean analog score for pain at the donor
      site was 7 of 10 points in the control group and 6 points in the study group (p =
      0.001) at one month and 3 and 2 points, respectively, at six months (p = 0.001).

PMID- 9160950
TI  - Avascular necrosis of the proximal humeral epiphysis after physeal fracture. A
      case report.

PMID- 9160951
TI  - Fracture-dislocation of the proximal part of the humerus with retroperitoneal
      displacement of the humeral head. A case report.

PMID- 9160952
TI  - Premature partial closure of the triradiate cartilage treated with excision of a
      physical osseous bar. Case report with a fourteen-year follow-up.

PMID- 9160953
TI  - Rotationplasty for the treatment of severe bone loss and infection of the distal
      end of the femur. A case report.

PMID- 9160954
TI  - Longitudinal deficiency of the fibula. Operative treatment.

PMID- 9160955
TI  - The beta-amyloid peptide, peptide self-assembly, and the emergence of biological
      activities. A new principle in peptide function and the induction of
      neuropathology.

PMID- 9160956
TI  - Neuropeptides and Alzheimer's disease pathology.

PMID- 9160957
TI  - Alterations of peptide metabolism and neuropeptidase activity in senile dementia
      of the Alzheimer's type.
AB  - Work in our laboratory has shown that in addition to previously characterized
      changes in the level of neuropeptides in SDAT brain, the activity of degradative
      enzymes responsible for peptide metabolism is also affected. In addition to other
      reported alterations in peptide metabolism, we have observed that SS-28
      degradation is increased in Brodmann area 22 whereas substance P degradation is
      increased in temporal cortex. Changes in the degradation of these neuropeptides
      known to be affected in SDAT correlate well with alterations in the activity of
      specific neuropeptidases. Trypsin-like serine protease activity is increased in
      SDAT Brodmann area 22 which parallels the increased degradation of SS-28. The
      activity of MEP 24.15 is decreased in temporal cortex which corresponds to the
      decreased degradation of substance P. Changes in the activity of these
      degradative enzymes in SDAT brain can potentially affect the action of other
      neuropeptide substrates because the neuropeptidases discussed here terminate the
      action of several neuropeptides. As more neuropeptide and degradative peptidase
      alterations are discovered in SDAT, greater emphasis may be placed on the role
      that peptides and neuropeptidases play in the progression of SDAT.

PMID- 9160958
TI  - Eclosion hormone action on the nervous system. Intracellular messengers and sites
      of action.

PMID- 9160959
TI  - Allatostatins: diversity in structure and function of an insect neuropeptide
      family.

PMID- 9160960
TI  - Insect neuropeptides of the pyrokinin/PBAN family accelerate pupariation in the
      fleshfly (Sarcophaga bullata) larvae.

PMID- 9160962
TI  - Distribution and processing of secretoneurin in the developing rat brain.

PMID- 9160963
TI  - Expression of cytokine genes during ontogenesis of the central nervous system.

PMID- 9160964
TI  - Ontogeny of prohormone convertases in rat prenatal development.
AB  - It has been well established that peptide precursors usually undergo limited
      proteolysis at pairs or single basic amino acids during their biosynthetic
      process. This posttranslational modification paradigm is common for numerous
      membrane-spanning and secreted proteins, neuropeptides, and peptide hormones of
      physiological significance, in which endoproteolytic cleavage is invariably
      essential for the accurate biosynthesis and full activity of the mature products.
      Establishment of an effective peptide profile is dependent on not only the
      presence of peptide precursor, but also the presence and the enzymatic
      specificities of cleavage enzymes. We have, therefore, characterized the spatial
      and temporal patterns of six subtilisin-like serine endoproteases known to be
      involved in proprotein processing, including furin, PC1, PC2, PC4, PC5, and
      PACE4, in rat prenatal development and related the results to the expression
      patterns of several peptide precursors. We have observed largely distinct and
      sometimes complementary expression patterns of individual PCs in various
      embryonic structures, suggesting PCs may be functionally distinct in processing
      different sets of proprotein substrates in development. From these studies,
      numerous tentative enzyme-substrate relationships in various embryonic structures
      have been proposed and should encourage more studies to test the in vitro
      cleavage potentialities of individual PCs toward these precursors. In the future,
      knowledge gained from these studies, when combined with insights gained from in
      vivo perturbation and genetic ablation studies, should lead to final
      comprehensive understanding of specific precursors cleaved by specific enzymes at
      specific cleavage sites in known spatial and temporal expression patterns during
      development.

PMID- 9160965
TI  - Use of nonpeptide antagonists to explore the physiological roles of neurotensin.
      Focus on brain neurotensin/dopamine interactions.

PMID- 9160966
TI  - Metal-ion sites as structural and functional probes of helix-helix interactions
      in 7TM receptors.

PMID- 9160967
TI  - Growth factor properties of VIP during early brain development. Whole embryo
      culture and in vivo studies.
AB  - Vasoactive intestinal peptide (VIP), a 28 amino acid neuropeptide widely
      distributed in the mammalian nervous system, has potent growth-related actions
      that influence cell division, neuronal survival, and neurodifferentiation. To
      address the potential effects of VIP on embryonic growth, whole postimplantation
      embryo cultures were used. After a 4-hour incubation, VIP stimulated growth as
      assessed by the following increases from control: embryonic volume (63%), DNA
      (103%), and protein content (63%), as well as the number of cells in S-phase
      (490%). No apparent histological abnormalities are produced by VIP. To assess the
      in vivo function of VIP in early CNS growth, a VIP antagonist (VA) was injected
      i.p. between E9 and E11. VA induced a dose reduction of the DNA (84% of controls)
      and protein (80% of controls) contents of the E11 head and a decrease of E17
      brain weight (87% of controls). In contrast, body growth was less affected by the
      antagonist. injections of VA for a longer period (E9 to E17) did not increase the
      severity of the microcephaly. By ex vivo autoradiography, GTP-sensitive VIP
      binding sites were detected in the germinative neuroepithelium between E9 and
      E11, but not between E13 and E15, during neuronal migration. These data
      demonstrate that VIP regulates mitogenic activity in the premigratory
      neuroepithelium. Although this effect is limited to a short ontogenic period,
      blockade of VIP by a specific antagonist induces a severe microcephaly.

PMID- 9160968
TI  - Neuropeptides and neuronal survival: neuroprotective strategy for Alzheimer's
      disease.

PMID- 9160970
TI  - Growth of the early postimplantation embryo. Regulation by high-affinity, GTP
      insensitive VIP receptors.

PMID- 9160969
TI  - Identity of neurotrophic molecules released from astroglia by vasoactive
      intestinal peptide.
AB  - Subnanomolar concentrations of VIP elicit a survival-producing action in CNS
      cultures composed of both astroglia and neurons. This neurotrophic action is
      mediated by a complex array of substances released by VIP from astrocytes.
      Included in this glial protein mixture is a cytokine (interleukin-1 alpha), a
      serine protease inhibitor (protease nexin I), and an extracellular stress protein
      (activity-dependent neurotrophic factor). In dissociated spinal cord cultures,
      all of these substances exhibit neuroprotection from neuronal cell death produced
      by electrical blockade with tetrodotoxin. All these substances produce neuronal
      cell death when test cultures are treated with neutralizing antisera to any one
      of them. They are all apparently necessary for the survival of a subpopulation of
      neurons that are dependent on spontaneous, excitatory neurotransmission. Our view
      is that these substances are components of a glia-derived environment that
      regulates, together with target-derived growth factors, the survival fate of
      developing neurons. In addition, it is our belief that some of these glia-derived
      substances will be found to have active roles in the injury response to the CNS
      or in the regulation of VIP-mediated growth in other tissues. Drugs based on
      these substances may provide therapeutic agents for the treatment of
      neurodegeneration and tumor growth.

PMID- 9160971
TI  - Regulation of neuropeptide expression in sympathetic neurons. Paracrine and
      retrograde influences.
AB  - Sympathetic neurons and other peripheral neurons exhibit a great deal of
      plasticity in their neuropeptide phenotype in adulthood. In this review, two
      phenotypes have been described in detail: that of normal sympathetic neurons and
      that of axotomized neurons. Two factors produced by nonneuronal cells, LIF and
      NGF, determine which of these phenotypes is expressed. Under normal conditions,
      the neurons receive NGF primarily, if not exclusively, from the target tissues
      they innervate. Prior to surgery, the nonneuronal cells within the ganglion and
      nerve tract express little, if any, LIF. This milieu favors the expression of NPY
      and suppresses the expression of VIP, galanin, and substance P (Fig. 6). After
      axotomy, however, this situation is reversed. The neuronal cell bodies are
      deprived of target-derived NGF and are exposed to LIF both within the ganglion
      and at the site of the injury (Fig 6). Both the removal of NGF and the exposure
      to LIF inhibit NPY expression, while promoting the expression of VIP and galanin.
      Expression of substance P after axotomy occurs primarily, if not entirely,
      because of the effects of LIF, with the removal of NGF playing no obvious role in
      the regulation of this peptide.

PMID- 9160972
TI  - Target regulation of VIP expression in sympathetic neurons.

PMID- 9160973
TI  - Target tissue influence on somatostatin expression in the avian ciliary ganglion.
AB  - Activin as a neurodifferentiation factor. Our studies of neurotransmitter
      expression have focused on the expression of neuropeptide transmitters in the
      avian ciliary ganglion (CG) and have examined the influence of choroidal vascular
      smooth muscle cells in regulating the differential expression of somatostatin in
      the CG. In these activities we have identified activin A as a potential target
      derived neurodifferentiation factor that can stimulate somatostatin expression in
      cultured CG neurons. In cultured CG neurons, activin can stimulate the expression
      of somatostatin in choroid neurons, the pattern of neurotransmitter expression
      found in vivo, and in the ciliary neurons that would normally not express
      somatostatin. In vivo, mRNA transcripts of the cActR-IIA appear to be expressed
      by both choroid and ciliary CG neurons. This suggests that activin might serve as
      an instructive factor in controlling neuropeptide phenotype. For activin to serve
      as an instructive factor requires that activin be produced by choroid smooth
      muscle target cells. Indeed, activin mRNA and activin-like immunoreactivity are
      found in choroid cells, in vitro. However, the lack of somatostatin expression by
      ciliary neurons suggests that activin is not produced by their targets, the iris
      and ciliary body. This simple view is countered by the observation that activin A
      mRNA is also present in the iris and activin-like immunoreactivity is detectable
      in the iris and ciliary body. Instead, the production of the specific activin
      inhibitor follistatin in the iris and ciliary body is likely to limit the
      availability of activin to only those neurites innervating the choroid layer,
      thus accounting for the differential expression of somatostatin in only the
      choroid CG neurons. This somewhat more complicated arrangement is similar to the
      mechanism thought to be employed for primary induction during frog embryogenesis.
      The observations reviewed here are all consistent with the hypothesized role for
      activin as a molecule whose availability to neurites in the target regulates
      neurotransmitter expression. Additional in vivo perturbation experiments are
      needed to further examine this hypothesis; nevertheless, activin appears as a
      strong candidate for a target-derived neurotransmitter differentiation factor.
      Activin's potential roles in differentiation: A wide variety of biological
      effects have been ascribed to activin. Initially identified and purified as a
      gonadal hormone stimulating the production and release of FSH from the pituitary,
      activin is also implicated in the stimulation of erythroid differentiation, as a
      modulator of follicular granulosa cell differentiation, as a mesodermalizing
      factor in both amphibian and avian early development, and as a component in
      establishing left-right axial patterning in the chicken embryo. Activin has also
      been found to be a survival factor for several neuronal cell lines and for rat
      embryonic neural retina cells in culture. However, activin is not a survival
      factor for chicken CG neurons in culture. Our observation that activin may play a
      function in target-derived control of neuropeptide expression adds yet another
      aspect to the list of its potential biological functions. In addition, activin
      shares regions of amino acid sequence identity with members of the TGF-beta
      superfamily, which includes the TGF-betas, Mullerian inhibitory substance,
      Drosophila decapentaplegic gene product, dorsalin, bone morphogenetic proteins,
      inhibin, and glial-derived neurotrophic factor. Interestingly, these are all
      factors that have effects upon cellular differentiation. Effects of activin on
      other neurons. Activin A--as well as two other TGF-beta superfamily members, BMP
      2 and BMP-6--has been shown to induce expression of mRNAs for several
      neuropeptides in cultured rat sympathetic neurons. In addition, activin A induces
      ChAT mRNA in cultured sympathetic neurons. (ABSTRACT TRUNCATED)

PMID- 9160974
TI  - Neonatal ACTH administration elicits long-term changes in forebrain monoamine
      innervation. Subsequent disruptions in hypothalamic-pituitary-adrenal and gonadal
      function.
AB  - The findings from this study demonstrated that the manipulation of the HPA system
      resulting from ACTH administration during neonatal development produces long
      term, differential effects, not only on adrenocortical activity, but also on the
      activity and integrity of the forebrain monoamine systems. Increased
      concentrations of the monoamines within the forebrain regions studied at days 7
      and 15, suggest a hastened maturation of these neural systems in animals
      neonatally treated with ACTH. The observed neurochemical alterations in these
      animals at one year are suggestive of an accelerated aging in the monoamine
      systems. A further consequence of these disturbances during development is an
      altered functioning of the HPG axis, as demonstrated by a delayed onset of
      puberty as previously reported, as well as significantly decreased proestrus
      plasma estradiol. Although deficits in sexual behavior also existed, it seems
      probable that these behavioral changes are a manifestation of altered neural
      systems regulating the ability to cope with a novel stimulus or situation, rather
      than a disruption of the "feminization" of the brain during sexual
      differentiation. This is in contrast to the male rat which exhibits permanent
      deficits in male typical sexual behavior following developmental ACTH treatment.
      The clinical relevance of these findings may be extensive. Perinatal exposure to
      events or agents that markedly increase ACTH and the corticosteroids may cause
      significant immediate and long-term changes in central monoamine functioning.
      These changes may constitute some of the most deleterious effects of stress
      exposure in infants and children. The alterations may be especially devastating
      in individuals with predispositions to stress-sensitive disorders such as
      anxiety, depression, and Tourette's syndrome. Finally, the use of ACTH in the
      treatment of infantile spasms may need to be reassessed in light of the possible
      long-term effects of ACTH on central monoamine functioning.

PMID- 9160975
TI  - Development neurobiology of the stress response: multilevel regulation of
      corticotropin-releasing hormone function.
AB  - The ability to respond to adverse environmental cues is present in the neonatal
      and infant rat, although in an immature form: A number of laboratories have
      demonstrated stress-induced elevations of plasma glucocorticoids during the first
      two postnatal weeks. The limbic and hypothalamic mechanisms controlling the
      hormonal stress-response during this period are not fully understood and are,
      therefore, the focus of this report. Both hypothalamic corticotropin-releasing
      hormone (CRH) and vasopressin contribute to the release of ACTH from the
      pituitary in the adult. The relative roles of these two peptides during the
      neonatal (first week) and infant (second week) developmental period, are
      controversial. Evidence is presented that argues strongly for a major role for
      CRH. Up-regulation of hypothalamic CRH synthesis is a major component in the
      mature stress response. CRH-mRNA levels in the hypothalamic PVN are increased
      with cold stress by ninth postnatal day, but not during the first postnatal week.
      Further, down-regulation of CRH gene expression by glucocorticoids (GC)
      constitutes a critical "shut-down" mechanism for the hormonal stress response. In
      vivo and in vitro experiments supporting the "immaturity" of GC feedback on CRH
      synthesis during the first postnatal week are described. CRH-mediated
      neurotransmission, in both the endocrine and neuronal effector arms of the
      response to stress may be modulated via alteration of receptor number. The first
      member of the CRH receptor family, CRF1, probably mediates the neuroendocrine
      effects of CRH. The developmental profile of CRF1-mRNA reveals several
      distinctive spatial and temporal patterns. In the hippocampal CA1, CA2, and CA3a
      peak (300-600% adult values) CRF1-mRNA is found on postnatal day 6. In the
      amygdala, CRH receptor mRNA levels are maximal on the ninth postnatal day (at
      180% of adult values). In cortex, a steady decline from high postnatal day 2
      levels results in adult levels by 12. These findings demonstrate distinct,
      regional, age-specific control of the synthesis of CRF1. Receptor expression
      profile may provide important information regarding modulation of the age
      specific roles of CRH in different regions. For example, a high ratio of
      hippocampus/amygdala receptors may preferentially activate negative hippocampal
      input to the hypothalamus during the neonatal period. Additionally, increased CRH
      receptor mRNA in the infant compared with the adult provides a mechanism for
      enhanced excitatory effect of the peptide at this age. In conclusion, increasing
      evidence exists for multiple control points of the early postnatal response and
      adaptation to stress. CRH synthesis in hypothalamus and amygdala, its sensitivity
      to GC feedback, and the abundance and distribution of at least two distinct CRH
      receptors in the limbic central nervous system and the pituitary are
      developmentally regulated. All serve as control points permitting an effective
      endocrine, autonomic, and behavioral response to stressful environmental cues.

PMID- 9160976
TI  - Maternal stress, HPA activity, and fetal/infant outcome.
AB  - Preliminary conclusions from our research include the possibility that each of
      the HPA products evaluated, even though correlated (e.g., ACTH and beta E), may
      be linked to unique and specific outcomes. Maternal stress during the 28-30 weeks
      of gestation is associated with birth outcome. Increased levels of psychosocial
      stress were significantly related to gestational age at birth and infant birth
      weight. Maternal stress during the third trimester was associated with increased
      maternal plasma levels of ACTH and cortisol. This finding is consistent with
      possible mechanisms whereby psychosocial stress influences birth outcome. CRH
      controls the timing of labor and delivery. Precocious elevation of CRH is related
      to the risk of preterm delivery. This system may be "stress-sensitive." Even
      though pregnant women may be immunized from stress, the stress signal that is
      transmitted (release of ACTH and cortisol) is amplified by the placental release
      of CRH. This possibility has at least two consequences: (1) influencing the
      timing of delivery and (2) desensitization of hypophyseal corticotrophs and
      further "protection" of the pregnant women from the results of stress (i.e.,
      release of ACTH and beta E). Beta E appears to influence fetal learning and
      perhaps the developing nervous system.

PMID- 9160977
TI  - Placental CRH modulates maternal pituitary adrenal function in human pregnancy.

PMID- 9160978
TI  - Steroid effects at the membrane level on oxytocin systems.

PMID- 9160979
TI  - Vasopressin deficiency and phase advancement shifts in circadian rhythms with
      nocturnal or diurnal feeding.

PMID- 9160980
TI  - c-Fos induction in the nucleus of the solitary tract of sodium-depleted rats by
      salt intake, peripheral bombesin, and the combination.

PMID- 9160981
TI  - Salt-loading induces decreased POMC mRNA levels, increased alpha-MSH
      immunoreactivity, and sustained elevated fos expression in rat pituitary
      intermediate lobe melanotropes.

PMID- 9160982
TI  - Peptidergic mechanisms of action in the suprachiasmatic nucleus.

PMID- 9160983
TI  - Cloning of a cDNA from stable fly which encodes a protein with homology to a
      Drosophila receptor for tachykinin-like peptides.

PMID- 9160984
TI  - Novel tachykinin-related peptides in the cockroach nervous system and intestine.
      Structure, distribution, and actions.

PMID- 9160986
TI  - Occurrence and diversity of neuropeptides from the crustacean hyperglycemic
      hormone family in arthropods. A short review.

PMID- 9160985
TI  - Dromyosuppressin and drosulfakinin, two structurally related Drosophila
      neuropeptides, are uniquely expressed in the adult central nervous system.
AB  - Drosophila myosuppressin (TDVDHVFLRFamide; DMS) and sulfakinin (FDDYGHMRFamide;
      DSK) have similar C-terminal structures. To determine the neuronal expression
      patterns of these structurally related peptides, we have generated DMS- and DSK
      specific antisera to multiple antigenic peptides and performed double-label
      immunochemistry with antisera raised on different animals of the same species
      host animal. Our data indicate that DMS and DSK staining patterns in the adult
      central nervous system are unique and nonoverlapping.

PMID- 9160987
TI  - Angiotensin-converting enzyme and the metabolism of regulatory peptides in
      insects.

PMID- 9160989
TI  - Molecular characterization of the Manduca sexta-type of allatostatin in the
      migratory moth Pseudaletia unipuncta.

PMID- 9160988
TI  - Biochemical characterization of mosquito kinin and related receptors.

PMID- 9160990
TI  - Persistence is not always a virtue: tort reform, civil liability for health care,
      and the lack of empirical evidence.
AB  - The efficacy of reforms in the civil system, including professional liability in
      the health care arena, depends upon the accuracy with which problems are defined.
      A growing empirical literature argues that the description of the civil justice
      system underlying the movement for tort reform in the health care arena is not an
      accurate one. Regardless, that description continues to be used successfully as
      the basis for a variety of enacted reforms. The interesting question now posed by
      some researchers is why that description persists despite its lack of empirical
      verification. This article summarizes the reformers' description; provides an
      overview of relevant empirical findings; and then draws on a theoretical
      literature in political science dealing with agenda-setting in the public policy
      process to answer that interesting question. The article concludes that the image
      persists because it is successful in a political, not rational, process in which
      appeals to emotion overshadow reasoned argument.

PMID- 9160991
TI  - Standard form contracts and contract schemas: a preliminary investigation of the
      effects of exculpatory clauses on consumers' propensity to sue.
AB  - This study investigated the extent to which exculpatory clauses deter consumers
      from pursuing their legal rights. Undergraduate participants (N = 101) were
      presented with two written vignettes and asked to imagine themselves as a
      consumer harmed by a contracted for service. Participants then read a contract
      and responded to questions assessing their likelihood of seeking compensation and
      their perceptions of the contract. The presence of exculpatory clauses, the
      severity of the harm, and the nature of the harm were varied. The data suggest
      that exculpatory clauses, if read, have a deterrent effect on propensity to seek
      compensation. Development of a psychological definition of contract schemas and
      implications for legal policy are discussed.

PMID- 9160992
TI  - Law school performance predicted by explanatory style.
AB  - The explanatory styles of 387 law students were assessed prior to law school
      using the Attributional Style Questionnaire (ASQ). Longitudinal performance
      measures were collected throughout law school and related to each student's
      initial explanatory style. In contrast to studies with undergraduates, students
      who made stable, global, and internal attributions for negative events combined
      with the converse attributions for success (typically called pessimists)
      outperformed more optimistic students on measures of grade point averages and law
      journal success. We discuss the limitations of current attributional research
      methodologies and suggest the prudent and cautious perspective necessary for law
      or skill-based professions may account for our findings.

PMID- 9160993
TI  - De novo protein biosynthesis responses to water stresses in wood frogs: freeze
      thaw and dehydration-rehydration.
AB  - Protein biosynthesis responses occurring during the postthaw (after 12 h freezing
      at -1.4 degrees C), dehydration (to 27 or 40% of total body water lost), or
      rehydration (after the loss of 40% of body water) were monitored in tissues of
      spring-collected wood frogs (Rana sylvatica) after intraperitoneal injection of
      35S-labeled methionine + cysteine. All six organs tested accumulated radiolabeled
      amino acids and organs of both thawing and rehydrating frogs held at 3-5 degrees
      C showed a linear increase in amino acid incorporation into the acid-precipitable
      protein fraction over time. By contrast, dehydrating animals showed little or no
      increment in protein bound radioactivity over the course of the stress, a result
      that may be indicative of metabolic suppression in organs when dehydration became
      severe. Isoelectrofocusing (IEF) and sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) were used to characterize the proteins synthesized by
      liver under each experimental state. IEF revealed both new peaks of 35S-labeled
      proteins and enhanced labeling of others in extracts from experimental animals,
      compared with controls. In particular, new synthesis of proteins with isoelectric
      points of about 6.0 was prominent and labeled proteins in this IEF peak persisted
      at 5, 10, or 24 h postinjection, becoming proportionally more important over
      time. SDS-PAGE analysis of the p(I) 6.0 peaks from thawed, dehydrated, and
      rehydrated frogs revealed the presence of one major low molecular weight protein
      in each case with molecular masses of 15, 13, and 21 kDa, respectively. These
      data indicate that the biochemical adaptations supporting freeze tolerance and
      dehydration tolerance in anurans include the stress-induced biosynthesis of a
      suite of proteins including the novel synthesis of selected specific proteins.
      These proteins may represent stress-related (or shock) proteins or may have
      specific roles in metabolic adaptation in each state such as in water and ionic
      balance or cell volume regulation.

PMID- 9160994
TI  - CNS axonal regeneration with peripheral nerve grafts cryopreserved by
      vitrification: cytological and functional aspects.
AB  - To test cool-warm protocols for storing peripheral nerves, 4-cm-long-nerve
      segments were removed from the hindleg of adult rats and cryopreserved using a
      vitrification solution (or cryoprotective mixture) containing a mixture of
      polyalcohols (2,3-butanediol, 1,2-propanediol, polyethylene glycol, and Belzer
      U.W. medium). Schwann cell viability and morphology were studied with regard to
      the effect of (i) cryoprotective mixture concentration (100, 50, and 30% diluted
      in human serum albumin at 4%), (ii) duration of exposure (10, 15, or 30 min in a
      single step) of nerves to the cryoprotective mixture, (iii) cooling rate (F1/F2,
      F3, and F4: 3, 12, and 231 degrees C/min, respectively), and (iv) type of
      replacement of cryoprotectant (T1, one step; or T2, perfusion) after warming.
      Nerves exposed 10 min to cryoprotective mixture 50% (2,3-butanediol, 1.926
      mol.liter-1; 1,2-propanediol, 3.063 mol.liter-1; polyethylene glycol, 0.084
      mol.liter-1; and Belzer U.W., 22.4 mosm-1) and cooled-warmed with the F2/F3/F4-T2
      protocols contained live and correctly cryopreserved Schwann cells. The capacity
      of these cryopreserved nerve segments (n = 6) to be subsequently repopulated by
      regenerating axons from central neurons was compared to that of fresh nerves when
      used as peripheral nerve autografts implanted within the spinal cord at the level
      of the descending respiratory pathways. All cryopreserved nerve grafts were
      successfully reinnervated by regenerated central axons. Unitary spontaneous
      action potentials propagated along these axons were assessed by recording the
      discharge of tested nervous filaments (T) from the grafts in artificially
      ventilated and paralyzed animals. Out of 535 T, 32 (6 +/- 1.2%) presented
      spontaneous unitary activity with respiratory (R, n = 2) and nonrespiratory (NR,
      n = 30) pattern of discharge. The T mean number, the occurrence rate referenced
      to the total number of T (R/T, NR/T, and R + NR/T) and the mean number of
      spontaneous units (R, NR, R + NR) were compared to those of fresh spinal
      peripheral nerve grafts. Except for T, cryopreserved peripheral nerve grafts
      contained statistically significantly (P < 0.05) less spontaneous R and NR
      unitary activity, which represented, respectively, 6.2 +/- 6.2 and 26.8 +/- 5.7%
      of that found in the control group. These data indicate that nerves cryopreserved
      with the protocols described above contain viable Schwann cells which constitute
      a suitable support to induce regeneration of central fibers. The effectiveness of
      nerve cryopreservation by vitrification is discussed with regard to Schwann cell
      viability following cool-warm protocols and to subsequent reinnervation of the
      cryopreserved peripheral nerve grafts.

PMID- 9160996
TI  - Chill sensitivity and cryoprotectant permeability of dechorionated zebrafish
      embryos, Brachydanio rerio.
AB  - The zebrafish (Brachydanio rerio) was used as a model for basic studies of the
      chilling sensitivity, permeability and toxicity of cryoprotectants. In both
      intact and dechorionated embryos, early-stage embryos (1.25, 1.5, 1.75, and 2 h)
      were more susceptible (P < 0.05) to chilling injury at 0 degrees C than late
      stage embryos (50, 75, and 100% epiboly and three-somite stage). Moreover,
      enzymatic removal of the chorion did not alter (P > 0.05) this pattern of
      sensitivity to chilling. Eight-hour zebrafish embryos tolerated short-term
      exposures to temperatures ranging from 4 to 23 degrees C for 3.5 h with no
      detrimental developmental effects. The permeability of dechorionated embryos to
      cryoprotectants was examined by measuring the kinetics of volumetric change at
      various developmental stages (16 cells to six somites or ca. 1.25 to 14 h
      postfertilization) at 28.5 degrees C. The dechorionated zebrafish embryo is
      composed of two complex cellular compartments (i.e., a large yolk and the
      developing blastoderm). From 40 to 100% epiboly, the volumes of yolk and
      blastoderm remained constant, ca. 82 and 18%, respectively. However, these
      volumes changed rapidly after epiboly. For example, at the six-somite stage, the
      yolk composed 61% of the total volume, whereas the blastoderm composed 39%. When
      three- and six-somite embryos were placed in 1.5 and 2.0 M cryoprotectants
      (dimethyl sulfoxide and propylene glycol), osmometric measurement of volume
      changes indicated no permeation of the cryoprotectants. However, some permeation
      was observed for six-somite embryos immersed in a 2.0 M methanol solution, but
      not for 3-somite embryos. For up to 30 min at room temperature, these
      cryoprotectant solutions were toxic to zebrafish embryos; however, 1.5 M glycerol
      and ethylene glycol solutions were. We conclude that the complex nature of the
      zebrafish embryo reduces the effectiveness and predictive value of light
      microscopical measurements for cryoprotectant permeability studies.

PMID- 9160997
TI  - Effects of cryopreservation of immune responses. XI. Heightened secretion of
      tumor necrosis factor-alpha by frozen human peripheral blood mononuclear cells.
AB  - In view of the wide usage of frozen PBMCs as stem cell support following high
      dose chemo- and/or radiotherapy, and the pleiotropic activities of tumor necrosis
      factor-alpha (TNF-alpha), the influences of freezing and radiation on LPS-induced
      TNF-alpha production by human peripheral blood mononuclear cells (PBMCs) were
      studied. Frozen PBMCs secreted significantly larger quantities of TNF-alpha than
      fresh cells. Blocking of endogenous IL-10 by neutralization with anti-IL-10
      monoclonal antibody resulted in further augmented and prolonged secretion of TNF
      alpha by both the fresh and frozen cells. In contrast, addition of exogenous IL
      10 to LPS-stimulated cultures inhibited TNF-alpha secretion. In vitro irradiation
      had an inconsistent effect on TNF-alpha production by the fresh PBMCs. Taken
      together, these results suggest that the endogenously hypersecreted TNF-alpha is
      indirectly responsible for the previously reported elevated IL-1-, IL-6-, and IL
      10-secreting capabilities of frozen PBMCs. They also indicate that the TNF-alpha
      induced IL-10 and then down-regulates the monocytes from further TNF-alpha
      secretion. Considering the vital role played by TNF-alpha in antimicrobial and
      antitumor activities, in the immune system, and in the pathogenesis of many acute
      and chronic diseases, the abilities of frozen cells to produce large quantities
      of TNF-alpha in response to infectious agents could have profound impact on
      patients receiving such frozen PBMCs as stem cell support following myeloablative
      therapies.

PMID- 9160998
TI  - Vitrification of mature mouse oocytes: improved results following addition of
      polyethylene glycol to a dimethyl sulfoxide solution.
AB  - Oocytes have been successfully cryopreserved using rapid and slow freezing
      procedures; however, variability in the success of replicates has limited its
      practical application. We have evaluated the potentially beneficial effects of
      adding 1 mg/ml of the polymer polyethylene glycol (PEG) (M(r) 8000) to a 6 M
      dimethyl sulfoxide (Me2SO) vitrification solution. Stepwise addition of
      cryoprotectant, either with or without PEG, was performed at room temperature (19
      21 degrees C). Oocytes were then loaded in plastic insemination straws and held
      in liquid nitrogen vapour at -140 degrees C for 3 min prior to storage in liquid
      nitrogen. Oocytes were warmed rapidly to room temperature and removal of
      cryoprotective agent was effected in the presence of 1 M sucrose solution.
      Viability was assessed by vitro fertilization. Oocytes cryopreserved after
      exposure to 6 M Me2SO in the absence of PEG showed 60% normality, 80%
      fertilization, and 55% development to blastocyst, median of 11 replicate
      experiments (191 oocytes). Individual replicates yield highly variable survival
      which ranged from 0 to 100%. The addition of PEG significantly improved oocyte
      normality to 95% (range 76-100%; median of 9 replicate experiments, 301 oocytes).
      Rates of fertilization (91%; 60-100%) and development of blastocyst (73%; 67-92)
      were also improved. The addition of 1 mg/ml PEG to a 6 M Me2SO solution resulted
      in greatly improved viability of oocytes following cryopreservation and vastly
      reduced the variability seen with Me2SO solution alone.

PMID- 9161000
TI  - Assessment of a bacteriocin-producing Lactobacillus strain in the control of
      spoilage of a cereal-based African fermented food.
AB  - As a part of a program to develop starter cultures aiding in the spoilage control
      and sanitation of African fermented foods, a cereal-based food ('ogi' and its
      solid form 'agidi' or 'eko') was prepared using a bacteriocin-producing
      Lactobacillus strain as the starter culture. The survival of an enterotoxigenic
      Escherichia coli strain was investigated in the naturally fermented food and in
      food fermented with the starter bacteriocin-producing Lactobacillus strain. An
      inhibition of E. coli was observed within 2 h of incubation in 'ogi' fermented
      with the bacteriocin producing strain. After 6 h, the viable count of E. coli in
      locally fermented 'ogi' was log 6.41 (2.54 X 10(6) CFU/mL), whereas in 'ogi'
      fermented with the bacteriocin producer it was reduced to log 1.70 (0.5 x 10(2)
      CFU/mL). Comparison of the shelf life of 'agidi' prepared from the naturally
      fermented food with that bacteriocin-producing starter culture showed that the
      latter had a better shelf life (kept for 11 d before spoilage occurred as
      compared with 7 d for the natural one). The results are discussed in terms of the
      potential of bacteriocin-producing cultures in the control and retardation of
      spoilage and food-forne infections in some African fermented foods.

PMID- 9160999
TI  - Ergot alkaloids--sources, structures and analytical methods.
AB  - Natural sources, i.e. fungal strains and species producing ergot alkaloids (EA),
      are surveyed together with the chemical structures of EA and a list of new
      natural EA discovered in the last three decades. Other topics include new
      efficient chromatographic methods (HPLC) for the separation and isolation of new
      natural EA and also immunological methods of EA detection.

PMID- 9161001
TI  - Ascomycetous yeasts associated with naturally occurring fruits in a tropical rain
      forest.
AB  - Fruits from twenty different species of angiosperms were collected during the
      period from November, 1991 to January, 1992. Two hundred and two strains of
      yeasts and yeast-like fungi were isolated, of which 74% showed ascomycetic
      affinity. Candida was the predominant genus, followed by (in descending order of
      occurrence): Cryptococcus, Kloeckera, Sporobolomyces, Pichia, Hanseniaspora and
      Bullera. Black yeasts and other strains showing basidiomycetic affinity were also
      isolated. The genus Candida represented the highest number of identified species
      and the greatest variety of associated substrates. Among the ascomycetes and
      their anamorphs, 38 species were identified, with Kloeckera apiculata being the
      most frequent among the isolates and the one which occurred in the largest
      variety of substrates. Some of the biotypes designated as Candida sp. A, B, C, D,
      E, F, G, H, I, and Pichia sp. did not correspond to the standard species
      description found in the literature, and may represent new species. The strains
      of yeasts isolated in this study were characterized and incorporated into the
      Tropical Culture Collection of the Fundaao Tropical de Pesquisas e Tecnologia
      Andre Tosello, Campinas, Sao Paulo.

PMID- 9161002
TI  - Accumulation of Ade+ reversions in isoauxotrophic stains of Saccharomyces
      cerevisiae allelic in RAD6 during adenine starvation.
AB  - A comparative method based on an analysis of accumulation of starvation-induced
      Ade+ reversions and cell death during adenine starvation was developed and
      exploited for estimating the role of RAD6 in the starvation-induced reversions.
      It was shown that inactivation of RAD6 function in Saccharomyces cerevisiae
      markedly enhances the accumulation of Ade+ reversions, and therefore it is likely
      that this gene is taking part in maintaining the low level of starvation-induced
      mutations in yeast cells.

PMID- 9161004
TI  - Primary Listeria monocytogenes infection in gestating mice.
AB  - The facultative intracellular Gram-positive bacterium Listeria monocytogenes is a
      food-borne pathogen of frequently underestimated importance. Pregnant women
      represent the high-risk group for L. monocytogenes infection. Abortion,
      stillbirth or neonatal infection can be the serious outcome of such an infection.
      Recovery from listeriosis, resistance mechanisms of the host and the effect of L.
      monocytogenes on fetal development still remain to be fully understood. The
      results of our experiments showed an increased susceptibility of gestating BALB/c
      mice to primary L. monocytogenes infection. The duration of listeriosis in
      gestating animals was almost twice longer than in the control group. Furthermore,
      it was clearly shown that the detrimental effect of L. monocytogenes on fetal
      development was more pronounced if the infection was acquired earlier during
      gestation.

PMID- 9161005
TI  - Structure of the insect head in ontogeny and phylogeny: a view from Drosophila.
AB  - Evolutionary, developmental and insect biologists are currently using a three
      pronged approach to study the evolution and development of the insect head.
      First, genetic manipulation of the fruit fly Drosophila melanogaster has led to
      the identification of many genes, including the segmentation and homeotic genes,
      that are important for embryonic pattern formation and development. Second, a
      comparison of orthologous gene expression patterns in other insects reveals that
      these regulatory genes are deployed in similar, yet distinct, patterns in
      different insects. Third, comparisons of embryonic morphology with gene
      expression patterns suggest that in general these genes promote a common insect
      body plan, but that variations in gene expression can often be correlated to
      variations in morphology. Here, we present a detailed review of the development
      of the cephalic ectoderm of Drosophila and extrapolate to development of a
      generalized insect head. Our analysis of the variations among insect species, in
      both morphology and gene expression patterns, conducted within an evolutionary
      framework supported by traditional phylogenies and paleontology provides the
      basis for hypotheses about the genetic factors governing morphologic and
      developmental evolution.

PMID- 9161007
TI  - The role of molecular chaperones in mitochondrial protein import and folding.
AB  - Molecular chaperones play a critical role in many cellular processes. This review
      concentrates on their role in targeting of proteins to the mitochondria and the
      subsequent folding of the imported protein. It also reviews the role of molecular
      chaperons in protein degradation, a process that not only regulates the turnover
      of proteins but also eliminates proteins that have folded incorrectly or have
      aggregated as a result of cell stress. Finally, the role of molecular chaperones,
      in particular to mitochondrial chaperonins, in disease is reviewed. In support of
      the endosymbiont theory on the origin of mitochondria, the chaperones of the
      mitochondrial compartment show a high degree of similarity to bacterial molecular
      chaperones. Thus, studies of protein folding in bacteria such as Escherichia coli
      have proved to be instructive in understanding the process in the eukaryotic
      cell. As in bacteria, the molecular chaperone genes of eukaryotes are activated
      by a variety of stresses. The regulation of stress genes involved in
      mitochondrial chaperone function is reviewed and major unsolved questions
      regarding the regulation, function, and involvement in disease of the molecular
      chaperones are identified.

PMID- 9161008
TI  - Proteoglycans and related components in plant cells.
AB  - After the context is set by a brief description of the plant cell surface,
      emphasis is placed on one class of cell surface components, the arabinogalactan
      proteins. An expansion of knowledge regarding the structure, expression, and
      function of these proteoglycans has been initiated and is being sustained through
      new experimental approaches, including the development of monoclonal antibody
      probes and the cloning of cDNAs corresponding to core polypeptides. An
      examination of the structure of both the polypeptide and carbohydrate components
      of arabinogalactan proteins is presented with emphasis placed on recently deduced
      core polypeptide sequences. Information about the biosynthesis and turnover of
      arabinogalactan proteins is incomplete, especially with regard to the
      carbohydrate component. Although functions of arabinogalactan proteins have not
      been clearly identified, regulated expression and several other lines of evidence
      point to involvement in plant reproductive development, pattern formation, and
      somatic embryogenesis, as well as in the underlying processes of cell division,
      cell expansion, and cell death. Arabinogalactan proteins are compared with animal
      proteoglycans and mucins, and the results of searches for plant analogues of
      other animal extracellular matrix components are examined.

PMID- 9161010
TI  - Incorporation of copper into the yeast Saccharomyces cerevisiae. Identification
      of Cu(I)--metallothionein in intact yeast cells.
AB  - Copper is an essential metal ion to many living organisms, including mammals, as
      it mediates a wide variety of important biochemical processes. At elevated
      concentrations, copper is extremely toxic to host cells. This paradoxical nature
      of copper has necessitated a highly regulated procedure for its cellular
      accumulation, transport, and excretion. One important group of proteins involved
      in eukaryotic copper speciation is the protein metallothionein. Luminescence
      microscopy data, emission, and circular dichroism spectral data are reported as
      copper is incorporated into metallothionein by the yeast Saccharomyces
      cerevisiae. These techniques provide information on the mechanism of copper
      uptake by S. cerevisiae. A two-stage kinetic mechanism for the uptake of copper
      from the growth medium by the yeast cells is observed. The first stage displays
      an uptake rate that is dependent on the initial copper concentration of the
      growth medium, and lasts for approximately 6 h. The second stage has a slower
      rate of copper uptake than the first, but the kinetics are independent of the
      initial copper concentration. Emission spectra recorded directly from the intact
      yeast cells (at 77 K) show that the cellular incorporation of copper proceeds via
      several species, eventually leading to storage of the copper in the form of Cu
      metallothionein. The photomicrographs of yeast cells grown in a copper-containing
      medium clearly show an orange luminescence, indicating the formation of a Cu(I)
      thiolate species. The identification of this species as copper-metallothionein
      was confirmed by measurement of the circular dichroism and emission properties
      following excretion and isolation of the copper-containing protein from the yeast
      cells. Analysis of the emission spectrum from S. cerevisiae Cu-metallothionein at
      77 K reveals two emission bands, centered at 570 and 700 nm. The high-energy
      emission band exhibits a two-component decay, with excited state lifetimes of
      4.70 and 48.5 microseconds. The low-energy emission exhibits one major decay
      component with a lifetime of 1.13 microseconds. A high-molecular-weight, copper
      containing species is also isolated from the yeast cells and is characterized
      spectroscopically.

PMID- 9161009
TI  - Ni++ as a competitive inhibitor of calcium transport in mitochondria.
AB  - The kinetics of Ca++ uptake in rat liver mitochondria have been studied using the
      potassium diffusion potential. The advantage of this approach is that in this
      condition, the mitochondrial respiratory rate is not the limiting step, and
      therefore the effects of Ni++ on the Ca++ carrier can be studied. Our results
      suggest that Ni++ is a competitive inhibitor of the Ca++ carrier, but it is not
      transported into the mitochondria.

PMID- 9161011
TI  - Crystal structure and characterization of the bismuth(III) compound with
      quinolone family member (ciprofloxacin). Antibacterial study.
AB  - Two bismuth(III) compounds of ciprofloxacin (cf) were synthesized. The crystal
      structure of one--(cfH2) (cfH) [BiCl6].2H2O (cfH2 = doubly protonated molecule of
      cf, cfH = protonated molecule of cf)--is presented and discussed. The compound
      crystallizes in the monoclinic space group P 21/c with a = 17.758(4), b =
      7.600(10), c = 31.908(6) A, beta = 101.03(2)0, Z = 4. The charge of the isolated
      hexachlorobismuthate(III) anions is compensated with protonated of molecules
      (ionic interactions). One of the cf molecules is protonated at carbonyl oxygen
      O(1) and nitrogen N(24) of the piperazine residue, and the other at N(24) only.
      Two water molecules participate in the hydrogen bond network. Antimicrobial
      activity of this compound was tested against different microorganisms. The
      results of TG and FT-IR measurements are also included.

PMID- 9161013
TI  - Phylogenetic evidence of mitochondrial DNA introgression among pocket gophers in
      New Mexico (family Geomyidae).
AB  - Mitochondrial DNA (mtDNA) variation in the cytochrome b gene was determined for
      two divergent taxa of pocket gophers, Thomomys bottae actuosus and T. b.
      ruidosae. These two taxa hybridize in a narrow contact zone, but introgression of
      nuclear markers such as allozymes or chromosomes does not extend much beyond the
      hybrid zone (Patton et al. 1979). We found that despite their distinctness, the
      two subspecies shared very similar mtDNA haplotypes. By a comparison of
      phylogenetic histories derived from nuclear markers (allozymes) and from mtDNA
      haplotypes sampled in different populations of T. bottae from New Mexico, we show
      that apparent similarity is due to an introgression of T. b. ruidosae mtDNA into
      T. b. actuosus nuclear background. Evidence of introgression is not limited to
      the present-day contact zone between these two taxa, but extends at least 75 km
      away from it. The actuosus haplotype coexists along with the ruidosae mtDNA in
      the Gallinas Mts., which are inhabited by otherwise pure T. b. actuosus, while
      further north only typical actuosus haplotypes were detected. Of several
      potential mechanisms which could lead to such a geographical pattern of
      variation, we argue that a combination of range shifts due to climatic
      fluctuations, and genetic drift are most likely. Horizontal gene transfers due to
      hybridization are historical events which seem rather common among pocket
      gophers. Although they can be identified with careful phylogenetic study using
      independent data sets, the potential for misinterpreting a gene tree as an
      organismal tree is great in this and other groups of animals.

PMID- 9161014
TI  - The occurrence of mountain hare mitochondrial DNA in wild brown hares.
AB  - If interspecific hybrids are fertile and backcross to either parental species,
      transmission of mitochondrial DNA over the species barrier can occur. To
      investigate if such transmission has occurred between the brown hare Lepus
      europeus Pall and the mountain hare L. timidus L. in Scandinavia, an analysis of
      genetic variation in mitochondrial DNA from 36 hares, collected from 15
      localities, was performed. Sequence divergence of mtDNA between species was
      estimated at 8 +/- 1% (SD). Intraspecific mtDNA sequence divergence varied
      between 0.09 and 0.38% in brown hares and 0.10 and 1.44% in mountain hares. In
      six out of 18 brown hares examined, two different haplotypes of mountain hare
      origin were detected, demonstrating a transmission of mtDNA haplotypes from
      mountain hares to brown hares. The results indicate that interspecific
      hybridization between the two species occurs in wild populations.

PMID- 9161015
TI  - Effect of PCR template concentration on the composition and distribution of total
      community 16S rDNA clone libraries.
AB  - Total DNA from sediment samples was isolated by a direct lysis technique.
      Purified DNA was used as template either undiluted or diluted 1:10 prior to
      polymerase chain reaction (PCR) amplification of 16S rRNA genes. Full-length
      inserts were analysed for restriction fragment length polymorphisms (RFLP) with
      the enzyme Cfo1, and the resulting distribution and abundance of RFLP patterns
      compared between the undiluted and diluted PCR reactions. Results indicate that
      for low PCR template concentrations, in the range from a few picograms to tens of
      picograms DNA, proportional representation of specific RFLP types was not
      reproducible upon template dilution, confirming that PCR amplification of 16S
      rDNA cannot be used directly to infer microbial abundance. In particular, only 15
      24% of the RFLP types recovered from a sample were present in both the undiluted
      and diluted extracts. We propose that very low template concentrations in the PCR
      generate random fluctuations in priming efficiency, which led to the contrast in
      RFLP types observed in the libraries from the undiluted and diluted extracts.

PMID- 9161016
TI  - A noninvasive method for distinguishing among canid species: amplification and
      enzyme restriction of DNA from dung.
AB  - Endangered San Joaquin kit foxes Vulpes macrotis mutica can be sympatrically
      distributed with as many as four other canids: red fox, gray fox, coyote and
      domestic dog. Canid scats are often found during routine fieldwork, but cannot be
      reliably identified to species. To detect and study the endangered kit fox, we
      developed mitochondrial DNA markers that can be amplified from small amounts of
      DNA extracted from scats. We amplified a 412-bp fragment of the mitochondrial
      cytochrome-b gene from scat samples and digested it with three restriction
      enzymes. The resulting restriction profiles discriminated among all five canid
      species and correctly identified 10 'unknown' fox scats to species in blind
      tests. We have applied our technique to identify canids species for an
      environmental management study and a conservation study. We envision that our
      protocol, and similar ones developed for other endangered species will be greatly
      used for conservation management in the future.

PMID- 9161017
TI  - Microsatellite loci in Columbian ground squirrels Spermophilus columbianus.

PMID- 9161018
TI  - Characterization of microsatellite loci in the endangered long-footed potoroo
      Potorous longipes.

PMID- 9161019
TI  - Isolation of tetranucleotide microsatellites from the Mexican jay Aphelocoma
      ultramarina.

PMID- 9161020
TI  - Similarity, connectionism, and the problem of representation in vision.
AB  - A representational scheme under which the ranking between represented
      similarities is isomorphic to the ranking between the corresponding shape
      similarities can support perfectly correct shape classification because it
      preserves the clustering of shapes according to the natural kinds prevailing in
      the external world. This article discusses the computational requirements of
      representation that preserves similarity ranks and points out the relative
      straightforwardness of its connectionist implementation.

PMID- 9161021
TI  - Dynamic model of visual recognition predicts neural response properties in the
      visual cortex.
AB  - The responses of visual cortical neurons during fixation tasks can be
      significantly modulated by stimuli from beyond the classical receptive field.
      Modulatory effects in neural responses have also been recently reported in a task
      where a monkey freely views a natural scene. In this article, we describe a
      hierarchical network model of visual recognition that explains these experimental
      observations by using a form of the extended Kalman filter as given by the
      minimum description length (MDL) principle. The model dynamically combines input
      driven bottom-up signals with expectation-driven top-down signals to predict
      current recognition state. Synaptic weights in the model are adapted in a Hebbian
      manner according to a learning rule also derived from the MDL principle. The
      resulting prediction-learning scheme can be viewed as implementing a form of
      expectation-maximization (EM) algorithm. The architecture of the model posits an
      active computational role of the reciprocal connections between adjoining visual
      cortical areas in determining neural response properties. In particular, the
      model demonstrates the possible role of feedback from higher cortical areas in
      mediating neurophysiological effects due to stimuli from beyond the classical
      receptive field. Simulations of the model are provided that help explain the
      experimental observations regarding neural responses in both free viewing and
      fixation conditions.

PMID- 9161022
TI  - SEEMORE: combining color, shape, and texture histogramming in a neurally inspired
      approach to visual object recognition.
AB  - Severe architectural and timing constraints within the primate visual system
      support the conjecture that the early phase of object recognition in the brain is
      based on a feedforward feature-extraction hierarchy. To assess the plausibility
      of this conjecture in an engineering context, a difficult three-dimensional
      object recognition domain was developed to challenge a pure feedforward,
      receptive-field-based recognition model called SEEMORE. SEEMORE is based on 102
      viewpoint-invariant nonlinear filters that as a group are sensitive to contour,
      texture, and color cues. The visual domains consists of 100 real objects of many
      different types, including rigid (shovel), nonrigid (telephone cord), and
      statistical (maple leaf cluster) objects and photographs of complex scenes.
      Objects were individually presented in color video images under normal room
      lighting conditions. Based on 12 to 36 training views, SEEMORE was required to
      recognize unnormalized test views of objects that could vary in position,
      orientation in the image plane and in depth, and scale (factor of 2); for
      nonrigid objects, recognition was also tested under gross shape deformations.
      Correct classification performance on a test set consisting of 600 novel object
      views was 97 percent (chance was 1 percent) and was comparable for the subset of
      15 nonrigid objects. Performance was also measured under a variety of image
      degradation conditions, including partial occlusion, limited clutter, color
      shift, and additive noise. Generalization behavior and classification errors
      illustrated the emergence of several striking natural shape categories that are
      not explicitly encoded in the dimensions of the feature space. It is concluded
      that in the light of the vast hardware resources available in the ventral stream
      of the primate visual system relative to those exercised here, the appealingly
      simple feature-space conjecture remains worthy of serious consideration as a
      neurobiological model.

PMID- 9161023
TI  - Image segmentation based on oscillatory correlation.
AB  - We study the image segmentation on the basis of locally excitatory, globally
      inhibitory oscillator networks (LEGION), whereby the phases of oscillators encode
      the binding of pixels. We introduce a lateral potential for each oscillators so
      that only oscillators with strong connections from their neighborhood can develop
      high potentials. Based on the concept of the lateral potential, a solution to
      remove noisy regions in an image is proposed for LEGION, so that it suppresses
      the oscillators corresponding to noisy regions but without affecting those
      corresponding to major regions. We show that the resulting oscillator network
      separates an image into several major regions, plus a background consisting of
      all noisy regions, and we illustrate network properties by computer stimulation.
      The network exhibits a natural capacity in segmenting images. The oscillatory
      dynamics leads to a computer algorithm, which is applied successfully to
      segmenting real gray-level images. A number of issues regarding biological
      plausibility and perceptual organization are discussed. We argue that LEGION
      provides a novel and effective framework for image segmentation and figure-ground
      segregation.

PMID- 9161024
TI  - Stochastic completion fields; a neural model of illusory contour shape and
      salience.
AB  - We describe an algorithm- and representation-level theory of illusory contour
      shape and salience. Unlike previous theories, our model is derived from a single
      assumption: that the prior probability distribution of boundary completion shape
      can be modeled by a random walk in a lattice whose points are positions and
      orientations in the image plane (i.e., the space that one can reasonably assume
      is represented by neurons of the mammalian visual cortex). Our model does not
      employ numerical relaxation or other explicit minimization, but instead relies on
      the fact that the probability that a particle following a random walk will pass
      through a given position and orientation on a path joining two boundary fragments
      can be computed directly as the product of two vector-field convolutions. We show
      that for the random walk we define, the maximum likelihood paths are curves of
      least energy, that is, on average, random walks follow paths commonly assumed to
      model the shape of illusory contours. A computer model is demonstrated on
      numerous illusory contour stimuli from the literature.

PMID- 9161025
TI  - Marr's theory of the neocortex as a self-organizing neural network.
AB  - Marr's proposal for the functioning of the neocortex (Marr, 1970) is the least
      known of his various theories for specific neural circuitries. He suggested that
      the neocortex learns by self-organization to extract the structure from the
      patterns of activity incident upon it. He proposed a feedforward neural network
      in which the connections to the output cells (identified with the pyramidal cells
      of the neocortex) are modified by a mechanism of competitive learning. It was
      intended that each output cell comes to be selective for the input patterns from
      a different class and is able to respond to new patterns from the same class that
      have not been seen before. The learning rule that Marr proposed was
      underspecified, but a logical extension of the basic idea results in a synaptic
      learning rule in which the total amount of synaptic strength of the connections
      from each input ("presynaptic") cell is kept at a constant level. In contrast,
      conventional competitive learning involves rules of the "postsynaptic" type. The
      network learns by exploiting the structure that Marr assumed to exist within the
      ensemble of input patterns. For this case, analysis is possible that extends that
      carried out by Marr, which was restricted to the binary classification task. This
      analysis is presented here, together with results from computer simulations of
      different types of competitive learning mechanisms. The presynaptic mechanism is
      best known in the computational neuroscience literature. In neural network
      applications, it may be a more suitable mechanism of competitive learning than
      those normally considered.

PMID- 9161026
TI  - Nitrite reductase expression is regulated at the post-transcriptional level by
      the nitrogen source in Nicotiana plumbaginifolia and Arabidopsis thaliana.
AB  - Higher plant nitrite reductase (NiR) is a monomeric chloroplastic protein
      catalysing the reduction of nitrite, the product of nitrate reduction, to
      ammonium. The expression of this enzyme is controlled at the transcriptional
      level by light and by the nitrogen source. In order to study the post
      transcriptional regulation of NiR, Nicotiana plumbaginifolia and Arabidopsis
      thaliana were transformed with a chimaeric NiR construct containing the tobacco
      leaf NiR1 coding sequence driven by the CaMV 35S RNA promoter. Transformed plants
      did not show any phenotypic difference when compared with the wild-type, although
      they overexpressed NiR activity in the leaves. When these plants were grown in
      vitro on media containing either nitrate or ammonium as sole nitrogen source, NiR
      mRNA derived from transgene expression was constitutively expressed, whereas NiR
      activity and protein level were strongly reduced on ammonium-containing medium.
      These results suggest that, together with transcriptional control, post
      transcriptional regulation by the nitrogen source is operating on NiR expression.
      This post-transcriptional regulation of tobacco leaf NiR1 expression was observed
      not only in the closely related species N. plumbaginifolia but also in the more
      distant species A. thaliana.

PMID- 9161027
TI  - Generation and maintenance of tandemly repeated extrachromosomal plasmid DNA in
      Chlamydomonas chloroplasts.
AB  - Unusual chloroplast transformants of Chlamydomonas reinhardtii that contain 2000
      copies of a mutant version of the chloroplast atpB gene, maintained as an
      extrachromosomal tandem repeat, have recently been described. In this paper
      studies have been undertaken to (i) address possible mechanisms for generating
      and maintaining the amplified DNA and (ii) determine whether it is possible to
      use chloroplast gene amplification to overexpress chloroplast or foreign genes.
      Data presented here indicate that high copy number transformants harbor
      characteristic rearrangements in both copies of the chloroplast genome large
      inverted repeat. These rearrangements appear to be a consequence of, or required
      for, maintenance of the amplified DNA. In an attempt to mimic the apparently
      autonomous replication of extrachromosomal DNA in the chloroplast, transformation
      was carried out with a plasmid that lacked homology with the chloroplast genome
      or with the same plasmid carrying a putative chloroplast DNA replication origin
      (oriA). Transformants were recovered only with the plasmid containing oriA, and
      all transformants contained an integrated plasmid copy at oriA, suggesting that
      establishment or maintenance of the extrachromosomal tandem repeat requires
      conditions that were not replicated in this experiment. To determine whether
      other genes could be maintained at high copy number in the chloroplast, plasmids
      carrying the wild-type atpB gene or the bacterial aadA gene were introduced into
      a high copy number transformant. Surprisingly, the copy number of the plasmid
      tandem repeat declined rapidly after the secondary transformation events, even
      when strong selective pressure for the introduced gene was applied. Thus,
      chloroplast transformation can either create or destabilize high copy number
      tandem repeats.

PMID- 9161029
TI  - A defect in synapsis causes male sterility in a T-DNA-tagged Arabidopsis thaliana
      mutant.
AB  - Fluorescence microscopy was used to study meiosis in microsporocytes from wild
      type Arabidopsis thaliana and a T-DNA-tagged meiotic mutant. Techniques for
      visualizing chromosomes and beta-tubulin in other plant species were evaluated
      and modified in order to develop a method for analyzing meiosis in A. thaliana
      anthers. Like most dicots, A. thaliana microsporocytes undergo simultaneous
      cytokinesis in which both meiotic divisions are completed prior to cytokinesis.
      However, two unique events were observed in wild-type A. thaliana that have not
      been reported in other angiosperms: (1) polarization of the microsporocyte
      cytoskeleton during prophase I prior to nuclear envelope breakdown, and (2)
      extensive depolymerization of microtubules just prior to metaphase II. The first
      observation could have implications regarding a previously uncharacterized
      mechanism for determining the axis of the metaphase I spindle during
      microsporogenesis. The second observation is peculiar since microtubules are
      known to be involved in chromosome alignment in other species; possible
      explanations will be discussed. A T-DNA-tagged meiotic mutant of A. thaliana
      (syn1), which had previously been shown to produce abnormal microspores with
      variable DNA content, was also cytologically characterized. The first observable
      defect occurs in microsporocytes at telophase I, where some chromosomes are
      scattered throughout the cytoplasm, usually attached to stray microtubules.
      Subsequent development stages are affected, leading to complete male sterility.
      Based on similarities to synaptic mutants that have been described in other
      species, it is suggested that this mutant is defective in synaptonemal complex
      formation and/or cohesion between sister chromatids.

PMID- 9161030
TI  - Interactions between the ABI1 and the ectopically expressed ABI3 genes in
      controlling abscisic acid responses in Arabidopsis vegetative tissues.
AB  - In Arabidopsis, the abscisic acid (ABA)-Insensitive ABI1 and ABI3 genes have been
      proposed to act in separate ABA signalling cascades. Recessive mutations in ABI3
      alter various physiological processes during seed development, whereas the
      dominant abi1 mutation inhibits ABA responses largely in vegetative tissues. The
      seed-specific ABI3 gene was ectopically expressed in the vegetative tissues of
      transgenic Arabidopsis plants carrying a transcriptional fusion between the CaMV
      35S promoter and the ABI3 cDNA. Genetic interactions between the ectopically
      expressed ABI3 and endogenous ABI1 genes were investigated by monitoring diverse
      ABA responses in vegetative tissues. Ectopic expression of ABI3 conferred to
      plantlets the ability to accumulate the seed-specific At2S33 and AtEm1 mRNAs in
      response to ABA, and the abi1 mutation inhibited this ABI3-dependent induction of
      AtEm1 by ABA. Furthermore, ectopic expression of ABI3 also influenced ABI1
      dependent responses that occur in wild-type vegetative tissues. Expression of
      ABI3 increased ABA induction of the Rab18 mRNA and ABA inhibition of root growth,
      and both responses were sensitive to the abi1 mutation in the presence as in the
      absence of ABI3. Finally, although ABI3 is thought to be a transcription
      activator and stomatal regulation is not known to involve transcriptional events,
      the ectopically expressed ABI3 gene suppressed the effect of the abi1 mutation on
      stomatal regulation. The present data demonstrate that ABI1 and ABI3 genetically
      interact in controlling diverse ABA responses in transgenic vegetative tissues.
      The possibility that the endogenous ABI1 and ABI3 genes may similarly act in a
      common ABA signalling pathway in seed is discussed with previous phenotypic
      studies of the abi1 and abi3 mutants.

PMID- 9161031
TI  - High mobility group proteins HMG-1 and HMG-I/Y bind to a positive regulatory
      region of the pea plastocyanin gene promoter.
AB  - A 268 bp region (P268) of the pea plastocyanin gene promoter responsible for high
      level expression has been shown to interact with the high mobility group proteins
      HMG-1 and HMG-I/Y isolated from pea shoot chromatin. cDNAs encoding an HMG-1
      protein of 154 amino acid residues containing a single HMG-box and a C-terminal
      acidic tail and an HMG-I/Y-like protein of 197 amino acid residues containing
      four AT-hooks have been isolated and expressed in Escherichia coli to provide
      large amounts of full-length proteins. DNase I footprinting identified eight
      binding sites for HMG-I/Y and six binding sites for HMG-1 in P268. Inhibition of
      binding by the antibiotic distamycin, which binds in the minor groove of A/T-rich
      DNA, revealed that HMG-I/Y binding was 400-fold more sensitive than HMG-1
      binding. Binding-site selection from a pool of random oligonucleotides indicated
      that HMG-I/Y binds to oligonucleotides containing stretches of five or more A/T
      bp and HMG-1 binds preferentially to oligonucleotides enriched in dinucleotides
      such as TpT and TpG.

PMID- 9161033
TI  - Programmed cell death in the root cortex of soybean root necrosis mutants.
AB  - The soybean root necrosis (rn) mutation causes a progressive browning of the root
      soon after germination that is associated with accumulation of phytoalexins and
      pathogenesis-related proteins and an increased tolerance to root-borne infection
      by the fungal pathogen, Phytophthora sojae. Grafting and decapitation experiments
      indicate that the rn phenotype is root-autonomous at the macroscopic level.
      However, the onset and severity of browning was modulated in intact plants by
      exposure to light, as was the extent of lateral root formation, suggesting that
      both lateral roots and the rn phenotype could be directly or indirectly
      controlled by similar shoot-derived factors. Browning first occurs in
      differentiated inner cortical cells adjacent to the stele and is preceded by a
      wave of autofluorescence that emanates from cortical cells opposite the xylem
      poles and spreads across the cortex. Before any visible changes in
      autofluorescence or browning, fragmented DNA was detected by TUNEL (Terminal
      deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling) in
      small clusters of inner cortical cells that subsequently could be distinguished
      cytologically from neighboring cells throughout rn root development. Inner
      cortical cells overlying lateral root primordia in either Rn or rn plants also
      were stained by TUNEL. Features commonly observed in animal cell apoptosis were
      confirmed by electron microscopy but, surprisingly, cells with a necrotic
      morphology were detected alongside apoptotic cells in the cortex of rn roots when
      TUNEL-positive cells were first observed. The two morphologies may represent
      different stages of a common pathway for programmed cell death (pcd) in plant
      roots, or two separate pathways of pcd could be involved. The phenotype of rn
      plants suggests that the Rn gene could either negatively regulate cortical cell
      death or be required for cortical cell survival. The possibility of a mechanistic
      link between cortical cell death in rn plants and during lateral root emergence
      is discussed.

PMID- 9161032
TI  - Gene targeting and instability of Agrobacterium T-DNA loci in the plant genome.
AB  - To develop a model system for studies of homologous recombination in plants,
      transgenic Nicotiana tabacum and Nicotiana plumbaginifolia lines were generated
      harbouring a single target T-DNA containing the negative selective codA gene
      encoding cytosine deaminase (CD) and the beta-glucuronidase (GUS) gene.
      Subsequently, the target lines were transformed with a replacement-type T-DNA
      vector in which the CD gene and the GUS promoter had been replaced with a
      kanamycin-resistance gene. For both Nicotiana species kanamycin-resistant lines
      were selected which had lost the CD gene and the GUS activity. One tobacco line
      was the result of a precise gene targeting event. However, most other lines were
      selected due to a chromosomal deletion of the target locus. The deletion
      frequency of the target locus varied between target lines, and could be present
      in up to 20% of the calli which were grown from leaf protoplasts. T-DNA transfer
      was not required for induction of the deletions, indicating that the target loci
      were unstable. A few lines were obtained in which the target locus had been
      deleted partially. Sequence analysis of the junctions revealed deletion of DNA
      sequences between microhomologies. We conclude that T-DNAs, which are stable
      during plant development as well as in transmission to the offspring, may become
      unstable during propagation in callus tissue. The relationships between callus
      culture, genetic instability and the process of T-DNA integration and deletion in
      the plant genome are discussed.

PMID- 9161034
TI  - Tam3 produces a suppressible allele of the DAG locus of Antirrhinum majus similar
      to Mu-suppressible alleles of maize.
AB  - Tam3 from Antirrhinum majus belongs to the Ac/Ds family of transposable elements.
      An allele of the DAG locus of Antirrhinum (dag::Tam3), which is required for
      chloroplast development and leaf palisade differentiation, has been generated by
      Tam3 insertion into the untranslated leader sequence of the gene. This allele
      gives rise to a cold-sensitive phenotype, where mutant tissue containing wild
      type revertant somatic sections is observed in the leaves of plants grown at 15
      degrees C, while leaves of plants grown at 25 degrees C appear near wild-type.
      The temperature sensitivity of dag::Tam3 results from expression of the DAG locus
      responding to the activity of the transposable element, the transposition of
      which is very sensitive to growing temperature. Genetic suppression of Tam3
      transposition, using the STABILISER locus, also results in suppression of the dag
      mutant phenotype. dag::Tam3 represents a Tam3-suppressible allele similar to
      those described for Mu transposons in maize. Suppression of the dag mutant
      phenotype in response to element inactivation appears to result from use of an
      alternative promoter at the 3' end of the Tam3 element. The production of
      suppressible alleles by an Ac-like element is discussed in relation to the
      mutagenic potential of plant transposons in producing complex genetic diversity.

PMID- 9161035
TI  - Abscisic acid and jasmonic acid activate wound-inducible genes in potato through
      separate, organ-specific signal transduction pathways.
AB  - Mechanical damage to leaf tissue causes an increase in abscisic acid (ABA) which
      in turn activates the biosynthesis of jasmonic acid (JA). The resulting higher
      endogenous JA levels subsequently activate the expression of wound-inducible
      genes. This study shows that JA induces the expression of different sets of genes
      in roots and leaves of potato plants. When roots of intact plants were treated
      with JA, high levels of proteinase inhibitor II (pin2), cathepsin D inhibitor,
      leucine aminopeptidase and threonine deaminase mRNAs accumulated in the systemic
      leaves. However, in the treated roots, very low, if any, expression of these
      genes could be detected. In contrast, a novel, root-specific pin2 homologue
      accumulated in the JA-treated root tissue which could not be detected in leaves,
      either systemic or those directly treated with JA. Application of okadaic acid
      and staurosporine revealed that a protein phosphorylation step is involved in the
      regulation of this differential response. In leaves, a protein phosphatase is
      required for the JA-induced expression of pin2 and the other genes analysed. This
      phosphatase activity is not necessary for the JA-induced expression of a pin2
      homologue in roots, suggesting the existence of different transduction pathways
      for the JA signal in these organs. The requirement of a protein phosphatase
      activity for JA-mediated gene induction has enabled identification of a JA
      independent pathway for ABA induction of pin2 and the other wound-inducible
      genes. This alternative pathway involves a protein kinase, and appears to be
      selective for wound-inducible genes. Our data suggest the presence of a complex,
      organ-specific transduction network for regulating the effects of the plant
      hormones ABA and JA on gene expression upon wounding.

PMID- 9161036
TI  - Expression and subcellular targeting of a soybean oleosin in transgenic rapeseed.
      Implications for the mechanism of oil-body formation in seeds.
AB  - Two genomic clones, encoding isoforms A and B of the 24 kDa soybean oleosin and
      containing 5 kbp and 1 kbp, respectively, of promoter sequence, were inserted
      separately into rapeseed plants. T2 seeds from five independent transgenic lines,
      three expressing isoform A and two expressing isoform B, each containing one or
      two copies of the transgene, were analysed in detail. In all five lines, the
      soybean transgenes exhibited the same patterns of mRNA and protein accumulation
      as the resident rapeseed oleosins, i.e. their expression was absolutely seed
      specific and peaked at the mid-late stages of cotyledon development. The 24 kDa
      soybean oleosin was targeted to and stably integrated into oil bodies, despite
      the absence of a soybean partner isoform. The soybean protein accumulated in
      young embryos mainly as a 23 kDa polypeptide, whereas a 24 kDa protein
      predominated later in development. The ratio of rapeseed:soybean oleosin in the
      transgenic plants was about 5:1 to 6:1, as determined by SDS-PAGE and
      densitometry. Accumulation of these relatively high levels of soybean oleosin
      protein did not affect the amount of endogenous rapeseed oleosin. Immunoblotting
      studies showed that about 95% of the recombinant soybean 24 kDa oleosin (and the
      endogenous 19 kDa rapeseed oleosin) was targeted to oil bodies, with the
      remainder associated with the microsomal fraction. Sucrose density-gradient
      centrifugation showed that the oleosins were associated with a membrane fraction
      of buoyant density 1.10-1.14 g ml-1, which partially overlapped with several
      endoplasmic reticulum (ER) markers. Unlike oleosins associated with oil bodies,
      none of the membrane-associated oleosins could be immunoprecipitated in the
      presence of protein A-Sepharose, indicating a possible conformational difference
      between the two pools of oleosin. Complementary electron microscopy
      immunocytochemical studies of transgenic rapeseed revealed that all oil bodies
      examined could be labelled with both the soybean or rapeseed anti-oleosin
      antibodies, indicating that each oil body contained a mixed population of soybean
      and rapeseed oleosins. A small but significant proportion of both soybean and
      rapeseed oleosins was located on ER membranes in the vicinity of oil bodies, but
      none were detected on the bulk ER cisternae. This is the first report of apparent
      targeting of oleosins via ER to oil bodies in vivo and of possible associated
      conformational/processing changes in the protein. Although oil-body formation per
      se can occur independently of oleosins, it is proposed that the relative net
      amounts of oleosin and oil accumulated during the course of seed development are
      a major determinant of oil-body size in desiccation-tolerant seeds.

PMID- 9161037
TI  - Exchanging sequence domains between S-RNases from Nicotiana alata disrupts pollen
      recognition.
AB  - In self-incompatible plants of the Solanaceae, the specificity of pollen
      rejection is controlled by a single multiallelic S-locus. Pollen tube growth is
      inhibited in the style when its single S-allele matches either S-allele present
      in the diploid pistil. Each S-allele encodes an S-RNase with a unique sequence. S
      RNases are secreted into the extra-cellular matrix of the transmitting tract
      which guides pollen tubes toward the ovary. Although it is known that S-RNases
      are the determinants of S-allele specificity in the pistil, it is not known how
      allele-specific information is encoded in the sequence. Therefore, we exchanged
      domains between S-RNases with different recognition specificities and expressed
      the chimeric proteins in transgenic plants to determine their effects on
      pollination behavior. Nine chimeric constructs were prepared in which domains
      from Nicotiana alata SA2- and SC10-RNases were exchanged. Among these nine
      constructs, the entire S-RNase sequence was sampled by exchanging single variable
      domains as well as larger blocks of contiguous sequences. The chimeric S-RNases
      retained enzymatic activity and were expressed at levels comparable to control
      transformants expressing SA2- and SC10-RNases. However, none of the chimeric S
      RNases caused rejection of either SA2- or SC10-pollen. We conclude that the
      recognition function of S-RNases can be disrupted by alterations in many parts of
      the sequence. It appears that the recognition function of S-RNase is not
      localized to a specific domain.

PMID- 9161038
TI  - Targeted misexpression of AGAMOUS in whorl 2 of Arabidopsis flowers.
AB  - In Arabidopsis, transcripts of the floral organ identity genes APETALA3,
      APETALA1, AGAMOUS, and PISTILLATA are expressed only in a subset of the floral
      organs. To test and extend present models for establishment of floral organ
      identity, we constructed a transgenic line that expresses the AGAMOUS gene under
      the control of the APETALA3 promotor (pAP3::AG). In wild-type flowers, AGAMOUS is
      expressed in the third and fourth floral whorls, whereas APETALA3 is expressed at
      high levels in whorls two and three. Under the control of the APETALA3 promotor,
      AGAMOUS is misexpressed in the second whorl of the flower. The organs in the
      second whorl of pAP3::AG flowers either fail to develop or develop as stamens.
      When pAP3::AG is crossed to the homeotic mutants apetala1, apetala3, pistilla,
      agamous and superman, novel floral phenotypes result. In pAP3::AG agamous-3
      mutants, the flowers are indeterminate and consist of a repetition of sepals and
      stamens, rather that sepals and petals, as is observed in agamous single mutants;
      the indeterminacy demonstrates that AG is required in the fourth whorl to make a
      flower determinate.

PMID- 9161039
TI  - Mutants of Arabidopsis thaliana with pleiotropic effects on the expression of the
      gene for beta-amylase and on the accumulation of anthocyanin that are inducible
      by sugars.
AB  - We identified a mutant of Arabidopsis thaliana ectotype Col-O in which
      significantly reduced levels of expression of the gene for beta-amylase (AT beta
      Amy) were detected in leaves in response to high concentrations of sucrose,
      glucose or fructose. Genetic studies, including a cross with transgenic plants
      that harbored the AT beta-Amy:GUS transgene with the promoter of AT beta-Amy,
      indicated that this phenotype was caused by a recessive mutation, Iba1, that
      affected expression of AT beta-Amy in trans. We also found a reduced level of
      sugar-induced expression of AT beta-Amy in the Landsberg erecta (Ler) ecotype
      compared with other ecotypes. This phenotype seemed to be due to a recessive
      trait, provisionally designated Iba2, that was linked to neither erecta nor Iba1.
      The Iba2 mutation also affected expression of AT beta-Amy:GUS transgene.
      Accumulation of starch and sugars after treatment of leaves with sucrose was not
      affected in the Iba1 mutant and Ler plants. However, both Iba1 mutant and Ler
      plants accumulated low levels of anthocyanin in response to sucrose, results that
      suggested the existence of some genetic linkage between regulation of the
      expression of AT beta-Amy and regulation of the accumulation of anthocyanin.
      Although the Iba1 and Iba2 mutations did not affect sugar-inducible gene
      expression in general, the expression of sugar-regulated genes other than the
      gene for beta-amylase was differentially affected in the Iba1 mutant and Ler
      plants. These results suggest that the sugar-regulated expression of many genes
      in plants might be mediated by multiple signal-transduction pathways.

PMID- 9161040
TI  - Localization of expression of KNAT3, a class 2 knotted1-like gene.
AB  - KNAT3 is a class 2 kn1-like gene in Arabidopsis thaliana. The RNA expression
      patterns of KNAT3 were characterized through the use of promoter-GUS fusion
      analysis and in situ hybridization. KNAT3 is expressed in several tissues and at
      several times during development. There are three main expression patterns: (1)
      during early organ development in young leaves, buds and pedicels; (2) at and
      near the junction between two organs at specific times during development,
      including the hypocotyl-root boundary in young seedlings, the anther-filament
      junction in mature flowers, and the ovule-funiculus and peduncle-silique
      boundaries in elongating siliques; and (3) in maturing tissues such as the style
      of elongating siliques, the petioles of maturing leaves, and most of the root.
      The varied expression patterns may indicate that KNAT3 plays several different
      roles in plants, depending on when and where it is expressed. Previous work on
      KNAT3 (Serikawa et al., 1996) indicated that expression of its RNA is regulated
      by light. Promoter-GUS seedlings were grown under different light conditions
      (continuous white, red and far-red light) to examine more closely the light
      regulation of the KNAT3 promoter. Continuous white light resulted in stronger
      overall GUS staining in the same patterns seen in seedlings grown under long-day
      conditions (cotyledons, upper hypocotyl and roots). Continuous red light resulted
      in reduced GUS expression in those same tissues. Continuous far-red light led to
      seedlings showing stronger staining in the hypocotyl and cotyledons than red
      light-grown plants but no staining in the roots. Thus, the KNAT3 promoter
      responds differently to red and far-red light.

PMID- 9161041
TI  - Domain exchanges between KNAT3 and KNAT1 suggest specificity of the kn1-like
      homeodomains requires sequences outside of the third helix and N-terminal arm of
      the homeodomain.
AB  - Domain exchange constructs that traded regions surrounding the homeodomain were
      constructed for two kn1-like genes, KNAT1 and KNAT3, and introduced into
      Arabidopsis thaliana under the control of the 35S CaMV promoter. The kn1-like
      homeodomain proteins all have the homeodomain located near the C-terminus of the
      protein, and also share a second conserved domain (the ELK domain) immediately N
      terminal to the homeodomain. Progeny were scored for the appearance of the KNAT1
      overexpression phenotype. A construct containing the KNAT3 N-terminus and the
      KNAT1 ELK- and homeodomain resulted in a KNAT1 overexpression phenotype,
      indicating that specificity mainly resides within the ELK- and homeodomain
      region. Further exchanges demonstrated that specificity probably does not arise
      from a single region within the ELK and/or homeodomain but rather requires
      sequences both N-terminal and C-terminal to residue 23 of the homeodomain.
      Further, in contrast to some animal homeodomains, KNAT1 does not utilize the
      residues of the N-terminal arm of the homeodomain for specificity.

PMID- 9161042
TI  - Potato guard cells respond to drying soil by a complex change in the expression
      of genes related to carbon metabolism and turgor regulation.
AB  - Altering stomatal function by a guard cell-targeted transgenic approach with the
      aim of increased stress tolerance and crop yield requires knowledge of the
      natural fluctuations of stomatal gene expression under stress conditions. We
      developed a fast method for the isolation of RNA from epidermal fragments of
      potato leaves (Solanum tuberosum L. cv. Desiree), demonstrated that this RNA
      preparation is highly enriched in guard cell transcripts and used this method to
      investigate the response of gene expression in guard cells to mild drought
      stress. Drought was applied in planta by withholding water over a period of 2-4
      days. In the following work responses observed under these conditions are called
      'long-term' in contrast to immediate (short-term) stomatal opening and closing
      responses to environmental stress. We observed both gene-specific increases and
      decreases of steady-state transcript levels. In particular, the mRNA levels of
      sucrose synthase and sucrose-phosphate synthase were elevated 5.5-fold and 1.4
      fold, respectively. In contrast, expression of an inwardly rectifying K+ channel
      from guard cells (kst1) and of a plasma membrane H(+)-ATPase (pha2) was reduced
      to 26% and 36%, respectively, of the expression in watered controls. In addition,
      expression of vacuolar invertase, UDP-glucose pyrophosphorylase, ADP-glucose
      pyrophosphorylase (large subunit), cytosolic glyceraldehyde-3-phosphate
      dehydrogenase, a sucrose/H+ cotransporter, and a novel isoform of
      phosphoenolpyruvate carboxylase were also reduced. Other genes exhibited
      unaltered expression. Compared with the response in whole leaves, the transcript
      levels of phosphoenolpyruvate carboxylase, vacuolar invertase, and cytosolic
      glyceraldehyde-3-phosphate dehydrogenase were regulated guard cell specifically.
      Most importantly, changes in steady-state transcript levels were complete before
      the onset of a decrease in leaf water potential, when drought-induced stomatal
      closure was already obvious. These data support the hypothesis that a systemic
      drought-stress signal acts not only on short-term stomatal movements but also on
      long-term gene expression in guard cells. Such long-term changes in gene
      expression might contribute to the fine-tuning of guard cell responses to
      environmental stimuli.

PMID- 9161043
TI  - Existence of three regulatory regions each containing a highly conserved motif in
      the promoter of plastid-encoded RNA polymerase gene (rpoB).
AB  - The plastid gene rpoB encodes a plastid-specific, DNA-dependent RNA polymerase. A
      study of a barley mutant, albostrians, indicated that rpoB itself is transcribed
      by a nuclear-encoded RNA polymerase. However, the molecular nature of the nuclear
      encoded RNA polymerase and mechanisms of the transcriptional regulation of rpoB
      expression have not been elucidated. Using an in vivo transient assay system for
      gene expression in plastids, the 5'-flanking region of rpoB from Arabidopsis
      thaliana in plastids of cultured BY-2 tobacco cells was analyzed. A series of
      deletion analyses of the 5'-flanking region indicated that there were two
      positive and one negative regulatory regions for rpoB expression. Comparison of
      the 5'-flanking sequences of rpoB among several plant species revealed the
      existence of three conserved motifs in these regions.

PMID- 9161044
TI  - Seal-promoting solutions and pipette perfusion for patch clamping plant cells.
AB  - Patch-clamp technology has greatly increased our knowledge of plant membrane
      transport. However, the success of patch clamping crucially relies on
      establishing a high resistance (G omega) seal between the membrane and the patch
      clamp pipette. This can prove problematic in many plant-cell preparations. It is
      therefore of great importance to develop protocols for protoplast isolation,
      maintenance and seal formation that improve seal rate. This study investigated
      whether the pH and the K+ and the Cl(-)concentration of the pipette solution had
      an effect on the seal formation. High pH and absence of K+ significantly promoted
      membrane sealing, whereas the concentration of Cl- had no effect. To reap the
      benefit of seal-promoting pipette solutions and yet retain the option to adjust
      this solution to experimental requirements, a pipette perfusion apparatus was
      implemented. The perfusion system was successfully applied in cell-attached
      patch, excised-patch and whole-cell configurations, using plasma membrane and
      tonoplast of three different species. The system enables complete solution
      exchange within minutes and is potentially of great benefit in the study of
      channel selectivity, the application of (cytoplasmic) channel blockers and the
      study of primary and secondary transport.

PMID- 9161045
TI  - Mass spectrometric gene diagnosis of one-base substitution from polymerase chain
      reaction amplified human DNA.
AB  - One-base substitution has been detected on the polymerase chain reaction (PCR)
      products amplified from human mutated DNA for the first time by using mass
      spectrometry. PCR fragments of 52 base pairs were produced on a collagen gene of
      an osteogenesis imperfecta patient's heterozygous DNAs. The products were
      digested with EcoRI restriction enzyme to liberate 3'-end adducts and purified by
      phenol + chloroform extraction, ammonium acetate addition and ethanol
      precipitation to remove sodium ions from the phosphoric acid backbone of the
      DNAs. Purified products were examined using an electrospray ionization mass
      spectrometer. Mass spectra showed four groups of fragment peaks with the expected
      molecular masses, which originate from the sense and antisense strands of the
      heterozygous DNAs.

PMID- 9161046
TI  - Synthesis and mass spectrometric behavior of some new nucleosides as potential
      anti-HIV agents.
AB  - The electron-impact (EI) mass spectrometric behaviour of a series of 8-aza
      purines derivatized with hydroxymethylcyclopentane and exhibiting cis-trans
      isomerization in the cyclopentane ring has been studied in detail with the aid of
      metastable-ion data. Specific fragmentation processes, present in both EI and
      mass analysed ion kinetic energy spectra of molecular species, allow
      characterization of the different pairs of stereoisomers. Contrary to what is
      observed in the case of purine analogs, the presence of a nitrogen atom in
      position 8 strongly inhibits fragmentation processes related to the heterocycle.

PMID- 9161047
TI  - Molecular heterogeneity of urinary proteins in wild house mouse populations.
AB  - Major urinary proteins (MUPs) from the urine of individual wild mice were
      characterized using electrospray ionization mass spectrometry (ESI-MS) and
      compared to MUPs from the urine of inbred mice. The wild mice showed considerable
      variation between individuals in the expression of a group of MUPs with similar
      masses. Some individuals excreted MUPs of unique molecular mass whilst some
      failed to express MUPs seen commonly in the other individuals. All the wild
      individuals contained proteins not previously observed in inbred mice. Urine from
      one individual was fractionated using anion exchange chromatography prior to
      analysis by ESI-MS. By analysing urine from inbred samples under the same
      conditions it was possible to relate, using mass and net charge in solution, MUPs
      from the wild sample to the MUPs that have been observed previously in inbred
      strains. This has allowed tentative identification of some MUPs from the wild
      mouse. The effect of collection history of urine from wild mice was also
      investigated. ESI-MS analysis of MUPs in a faecally contaminated sample showed
      the loss of a C-terminal tripeptide when compared to an uncontaminated sample
      from the same mouse, consistent with the presence of a specific endopeptidase.
      Similarly a sample of pooled urine provided by twelve individuals trapped from
      the same population showed evidence of loss of the C-terminal dipeptide.

PMID- 9161048
TI  - Next-generation Fc chimeric proteins: avoiding immune-system interactions.

PMID- 9161049
TI  - Phage display and antibody engineering: a French overview.

PMID- 9161051
TI  - HIV integrase: a target for AIDS therapeutics.
AB  - HIV integrase catalyses the incorporation of virally derived DNA into the human
      genome. This unique step in the virus life cycle provides a variety of points for
      intervention and hence is an attractive target for the development of new
      therapeutics for the treatment of AIDS. In this review we summarize current
      knowledge of the function of this enzyme and discuss some of the obstacles to the
      development of appropriate drugs.

PMID- 9161052
TI  - Transient suppression of macrophage functions by liposome-encapsulated drugs.
AB  - Macrophages play an important role in host defense reactions, for example, by
      phagocytosis of particulate materials. This process also results in the rapid
      removal of targeting devices such as liposomes and adenovirus vectors and of non
      autologous grafted cells and materials. Another aspect of macrophage function is
      their production and secretion of proinflammatory cytokines. Transient and organ
      specific suppression of macrophage function by liposome-mediated manipulation has
      been shown to improve the efficacy of drug and gene targeting and to reduce the
      symptoms of inflammatory reactions.

PMID- 9161054
TI  - The quest for accountability of quality in health care.

PMID- 9161053
TI  - Bacterial surface display: trends and progress.
AB  - Heterologous surface display on Gram-negative bacterial was first described a
      decade ago and is now an active research area. More recently, strategies for
      surface display on Gram-positive bacterial have also been devised and these carry
      some inherent advantages. Bacterial surface display has found a range of
      applications in the expression of various antigenic determinants, heterologous
      enzymes, single-chain antibodies, polyhistidyl tags and even entire peptide
      libraries. This article explains the basis of bacterial surface display and
      discusses current uses and possible future trends of this emerging technology.

PMID- 9161055
TI  - Health care spending, delivery, and outcome in developed countries: a cross
      national comparison.
AB  - This study examines the trend of health care spending, availability and use of
      medical services, and aggregate health outcome of the 24 industrialized member
      countries of the Organization for Economic Cooperation and Development (OECD).
      Major differences between the United States and other OECD countries are
      highlighted and discussed. The results of the study demonstrate that, over the
      past four decades, the United States has been spending more and accomplishing
      less when compared with other industrialized nations. The United States needs to
      learn from the successful experience of other nations. Redesigning the system of
      health care delivery in the United States may be the only viable option to
      improve the quality of health care.

PMID- 9161056
TI  - The impact of restraints on nursing home resident outcomes.
AB  - This article is an examination of the impact of physical restraints on physical
      activities of daily living (PADL), walking, and orientation to reality outcomes
      among nursing home residents. Computerized assessment data for a cohort of 5073
      Virginia Medicaid nursing home admissions with complete data for their first and
      second post-admission assessments were analyzed. Multiple regression analysis was
      used to compare the outcomes of restrained and nonrestrained residents, after
      controlling statistically for the influence of case mix variables that might
      impact outcomes. Restraint use was associated with increased PADL dependence and
      disorientation for residents restrained at first and second assessment, both
      assessments, and either assessment. Restraint was associated with increased
      walking dependence for residents restrained at their second assessment and either
      assessment.

PMID- 9161057
TI  - Declines in hospital mortality associated with a regional initiative to measure
      hospital performance.
AB  - To determine changes in hospital mortality that occurred in association with the
      dissemination of data by a regional initiative to profile hospital performance,
      we conducted a retrospective cohort study of patients admitted before and
      subsequent to dissemination of comparative data in 1992. The analysis included
      101,060 consecutive eligible discharges from 30 hospitals in Northeast Ohio with
      eight diagnoses: acute myocardial infarction, congestive heart failure (CHF),
      obstructive airway disease, gastrointestinal hemorrhage, pneumonia, stroke,
      coronary artery bypass surgery, and lower bowel resection. Baseline (1991, N =
      35,629) mortality rates were compared to rates during three subsequent periods
      (July-December 1992, N = 20,392; January-June 1993, N = 23,070; and July-December
      1993, N = 21,969). Mortality rates were risk-adjusted using validated
      multivariable models based on data abstracted from patient's medical records. For
      all conditions, risk-adjusted mortality declined from a baseline rate of 7.5% to
      rates of 6.8%, 6.8%, and 6.5%, respectively, during the three subsequent periods.
      Using weighted linear regression analysis to estimate trends across periods,
      declines in mortality rates were significant for CHF (0.50% per period; P =
      0.002) and pneumonia (0.38% per period; P = 0.03). We conclude that hospital
      mortality declined in association with the dissemination of comparative data.
      Although changes in hospital care were not directly examined, the results suggest
      that initiatives to examine provider performance may have a beneficial impact on
      quality of care.

PMID- 9161058
TI  - The use of administrative data to risk-stratify asthmatic patients.
AB  - In this article, a simple methodology to risk-stratify asthmatics is presented
      and validated. Such a model can be used to identify those high risk and more
      severely ill asthmatics who could benefit the most from case management and
      increased educational efforts. Using logistic regression, the model was created
      to predict the probability of an asthma-related admission among all asthmatics
      who were members of a large HMO during calendar year 1994 (N = 54,573). The model
      used data from pharmacy, laboratory, and specialist claims, as well as encounter
      and demographic data available in U.S. Healthcare's administrative database. A
      member's prior asthma-specific utilization patterns, pharmaceutically determined
      severity of illness, and length of enrollment in the managed care organization
      had the most influence on the equation. A cross-validation of the model confirms
      how administrative data can be used to accurately risk-stratify those with a
      chronic disease. Finally, some additional research possibilities associated with
      the identification of high risk subscribers using only administrative data are
      outlined.

PMID- 9161059
TI  - Reengineering a surgical service line: focusing on core process improvement.
AB  - Integrating principles from a variety of theory has led to the development of a
      conceptual framework for reengineering in a clinical care delivery setting to
      improve the value of services provided to the customer. A conceptual framework
      involving the identification of three high level core processes to reengineer can
      provide clarity and focus for clinicians to begin directing reengineering
      efforts. Those core processes are: clinical management of the patient's medical
      needs, patient operational processes to support the clinical processes, and
      administrative decision-making processes to support the implementation of the
      clinical and operational processes. Improvement in any one of these areas has the
      potential to increase value, but the concurrent targeting of these core processes
      for reengineering has provided a synergy that has accelerated the achievement of
      the desired outcomes in the area of surgical services.

PMID- 9161061
TI  - Denial of care for financial reasons.

PMID- 9161060
TI  - Using quality and cost for employee incentives in a reengineered hospital
      setting.
AB  - The Mount Sinai Hospital is reengineering its inpatient services to increase the
      quality of patient care and achieve greater operational efficiency. The central
      component of this redesign has been the establishment of "care centers," which
      are administratively and fiscally separate "hospitals within the hospital." To
      promote quality and financial goals set for each care center, a novel employee
      incentive compensation program was created. Performance on both quality and
      financial indicators determines the level of bonus payments to hourly employees.
      The incentive compensation plan was initiated in the first quarter of 1996. By
      achieving two of the three performance targets, employees earned a bonus of 6% of
      base salary for the first two quarters. Nurses and pharmacists did not accept
      bonus payments because of collective bargaining agreements. The early experience
      of the Cardiac Care Center has been highly favorable. Changes are planned to
      improve the process further.

PMID- 9161062
TI  - Immunisation in the year 2020 and beyond.

PMID- 9161063
TI  - Have you had your quota of nearest birthdays?

PMID- 9161064
TI  - Whither private health insurance?

PMID- 9161065
TI  - A health profile of adults in a Northern Territory aboriginal community, with an
      emphasis on preventable morbidities.
AB  - We conducted a brief health survey of adults in an isolated Northern Territory
      Aboriginal community, whose standardised mortality rates are the second highest
      in Australia. The screen revealed high rates of smoking and excessive drinking,
      of preventable infections and their sequelae, and of hypertension, insulin
      resistance, diabetes and renal disease. The infectious morbidities were more
      pronounced and the life-style morbidities almost entirely new since a health
      screen in 1957. Most morbidities were strongly associated with identifiable risk
      factors, such as overweight, smoking, excessive drinking, skin sores and scabies,
      all of which which are amenable to modification. Problems with food supply and
      pricing, poor food choices and diversion of money to cigarettes, beer and
      gambling all contributed to poor nutrition. Low birthweight probably compounds
      the risk for serious adult disease associated with these environmental
      influences. This profile highlights the failure of current systems to deal with
      health needs. Improvements in infrastructure, education and employment, and
      reinvigoration of preventive and primary health care programs, assumption of
      responsibility for health by the community and by individuals themselves, and
      better management of existing morbidities are essential to rectifying this
      shameful situation.

PMID- 9161066
TI  - Selection bias from sampling frames: telephone directory and electoral roll
      compared with door-to-door population census: results from the Blue Mountains Eye
      Study.
AB  - Many Australian public health research studies use the telephone directory or the
      electoral roll as a sampling frame from which to draw study subjects. The
      sociodemographic, disease-state and risk-factor characteristics of subjects who
      could be recruited using only the telephone directory or only the electoral roll
      sampling frames were compared with the characteristics of subjects who would have
      been missed using only these sampling frames, respectively. In the first phase of
      the Blue Mountains Eye Study we interviewed and examined 2557 people aged 49 and
      over living in a defined postcode area, recruited from a door-to-door census.
      This represented a participation rate of 80.9 per cent and a response rate of
      87.9 per cent. The telephone directory was searched for each subject's telephone
      number and the electoral roll was searched for each subject. Subject
      characteristics for those who were present in each of these sampling frames were
      compared with the characteristics of those subjects not included in the sampling
      frames. The telephone directory listed 2102 (82.2 per cent) of the subjects, and
      115 (4.5 per cent) had no telephone connected. The electoral roll contained 2156
      (84.3 per cent) of the subjects, and 141 subjects (5.5 per cent) could not be
      found in either the electoral roll or the telephone directory. Younger subjects,
      subjects who did not own their own homes and subjects born outside of Australia
      were significantly less likely to be included in either of these sampling frames.
      The telephone directory was also more likely to exclude subjects with higher
      occupational prestige, while the electoral roll was more likely to exclude
      unmarried persons and males. Researchers using the telephone directory and
      electoral roll to select subjects for study should be aware of the potential
      selection bias these sampling frames incur and need to take care when
      generalising their findings to the wider community.

PMID- 9161068
TI  - Dietary intake of Australian smokers and nonsmokers.
AB  - The 1983 National Dietary Survey of Adults and the 1983 Risk Factor Prevalence
      Survey No. 2, conducted on the same subjects, provided an opportunity to examine
      the nutrient intakes of smokers (1024 men and 785 women) and nonsmokers (1974 men
      and 2421 women). The nutrients analysed were energy (kJ); fat (g/day and
      contribution to energy); starch (contribution to energy); dietary fibre (g/day
      and g/1000 kJ); alcohol (g/1000 kJ); polyunsaturated/saturated fats ratio;
      cholesterol, niacin, vitamin C, calcium, iron, zinc and magnesium (mg/1000 kJ);
      and vitamin A, thiamin and riboflavin (microgram/1000 kJ). For both men and
      women, nonsmokers have a significantly higher intake of starch, dietary fibre
      (g/day and g/1000 kJ), thiamin, vitamin C, calcium and magnesium than smokers,
      who have a significantly higher intake of alcohol. Male smokers also have a
      higher intake of energy and cholesterol, but a lower intake of riboflavin, than
      nonsmokers. These differences in nutrient intakes suggest that nonsmokers consume
      a more nutritious diet than smokers, in regard to having a higher intake of fruit
      and vegetables, wholegrain cereals and milk and milk products. There is a highly
      statistically significant association between smoking status and hazardous intake
      of alcohol. Both men and women who smoke have a significantly lower body mass
      index (BMI), than nonsmokers or ex-smokers.

PMID- 9161067
TI  - Face-to-face household interviews versus telephone interviews for health surveys.
AB  - The purpose of this study was to compare response distributions in health surveys
      for two interview modes: face-to-face household interviews and telephone
      interviews. There were two samples of the Perth metropolitan general population
      aged 16 to 69 years: a face-to-face household sample (n = 1000) and a telephone
      sample (n = 222). The samples were generated by probability-based methods
      commonly used by commercial market research organisations. The surveys occurred
      in August-September 1992 as part of a larger statewide survey component of a
      three-year evaluation of the Western Australian Health Promotion Foundation.
      Respondents were drawn from a two-stage cluster sample based on private dwellings
      for personal interviews, and from randomly selected listed and unlisted private
      numbers for telephone interviews. Although the samples did not differ
      significantly on a number of variables, the telephone sample was significantly
      higher in residential social status; there was significantly lower reporting of
      smoking and lower unsafe alcohol consumption in the telephone sample:
      significantly higher proportions of the telephone sample were in Prochaska's
      'action' stage of change for several health behaviours; and there was
      significantly greater recall of health messages in the telephone sample. Health
      researchers should treat comparisons between different survey modes with caution,
      and should be aware that campaign evaluations using telephone surveys and
      household surveys may yield substantially different results.

PMID- 9161069
TI  - Whose diet has changed?
AB  - The same questions about diet were asked in two community-based surveys conducted
      in the Hunter Region of New South Wales in 1983 and 1994. There were substantial
      changes in diet over the period; for example, the proportion of respondents who
      reported using low-fat or skim milk increased from 25 per cent to 51 per cent,
      the proportion eating meat fewer than five times a week doubled from 21 per cent
      to 42 per cent and the proportion eating fewer than three eggs per week increased
      from 55 per cent to 80 per cent. In both surveys, women reported eating a
      healthier diet than men, and older people and those of higher socioeconomic
      status reported better diets than younger people or people with less education or
      lower status occupations. The surprising finding was that over the 11-year period
      the changes in patterns of food consumption were remarkably similar across all
      strata of the population. The conclusions are that wide-spread dietary change is
      possible. However, the changes in the last decade related mainly to reducing the
      risk of cardiovascular disease; similar behavioural changes to reduce the risk of
      diet-related cancer are required.

PMID- 9161070
TI  - Exercise profile and subsequent mortality in an elderly Australian population.
AB  - Although the importance of exercise as a public health issue is increasingly
      recognised, little attention has been paid to exercise in very old people. We
      examined exercise patterns in 1788 subjects aged 70 years and over who were
      participating in the Australian Longitudinal Study of Ageing. In the two weeks
      before interview, 39 per cent of subjects had taken no exercise and only four per
      cent had exercised vigorously. When compared with those who took no exercise,
      exercisers were more likely to be male and younger, to self-report better health,
      to be former smokers and regular alcohol users. Mortality rates at two years
      follow-up were inversely related to the level of exercise at baseline. This
      research indicates that exercise is important for the very old as well as younger
      groups.

PMID- 9161071
TI  - Obstetric outcomes and infant birthweights for Vietnamese-born and Australian
      born women in southwestern Sydney.
AB  - The southwestern Sydney area has the highest population of Vietnamese immigrants
      in New South Wales. The purpose of this study was to identify differences in
      obstetric outcomes and birthweights of infants of Vietnamese-born women and
      Australian-born women in southwestern Sydney during 1991. There was a higher
      incidence of gestational diabetes and a lower incidence of pre-eclampsia in
      Vietnamese-born women. The rate of induction of labour for Australian-born women
      (23.7 per cent) was almost double the rate for Vietnamese-born women (12.9 per
      cent). Birthweights of infants of vietnamese-born women were significantly lower
      at the 10th, 50th and 90th percentile. The use of racially appropriate growth
      charts will reduce overdiagnosis of growth-restricted infants and therefore
      unnecessary treatment. These findings highlight the need to take ethnic
      differences into account when planning health care.

PMID- 9161072
TI  - Opportunistic blood lead testing in a paediatric inpatient population.
AB  - We report a simple protocol which has potential to estimate community paediatric
      blood lead levels using opportunistic testing. Permission to use leftover blood
      for a lead assay was sought from parents or guardians of 397 children one month
      to 13 years of age who were admitted to general paediatric wards of John Hunter
      Hospital, Newcastle, between May and August 1993 and who had blood for a full
      blood count taken for any reason. Results were reviewed by a medical officer and
      returned to parents. Where a child's blood lead level was of concern according to
      National Health and Medical Research Council guidelines, the child was referred
      to a specialist paediatrician for clinical assessment. Written consent was
      received from the parents or guardians of 95.5 per cent of eligible children (n =
      379); 93.4 per cent of responders (354 of 379) had blood suitable for testing,
      giving an overall result rate of 89.2 per cent (354 of 397). The mean blood lead
      level for the whole group was 5.3 micrograms/dL. The highest blood lead level for
      any age group was 6.4 micrograms/dL in the 36 to < 60 month age group.
      Stratification by geographical area showed a trend in increasing blood lead with
      increasing population density and areas where lead polluting industries exist.
      The approximate cost per result achieved was $40. This opportunistic survey
      method provides a promising technique for obtaining data on community blood lead
      levels. It may be a practical and resource-efficient alternative to large-scale
      community surveys. Further studies are under way to validate the method as a
      community surveillance tool.

PMID- 9161073
TI  - Health risk and behaviour of out-of-school 16-year-olds in New South Wales.
AB  - This study describes the health risks and health behaviour of a sample of 283 out
      of-school 16-year-olds in New South Wales. We sampled study participants through
      the Commonwealth Employment Service offices in 1994 using a multistage sampling
      procedure. Of those surveyed, 129 responded to a letter inviting them to
      participate and 154 were recruited opportunistically. This paper describes the
      study methods and results for self-reported binge drinking, weekly use of tobacco
      and marijuana, sexual abuse, physical abuse, drink-driving, violence, and use of
      health services, by sex and method of recruitment. High rates of substance use
      were observed. Reported substance use in the out-of-school group was consistently
      higher than for 16-year-olds in school, except for binge drinking for girls
      recruited by letter. Of the out-of-school group, 34 per cent reported weekly use
      of tobacco, marijuana and also binge drinking. Boys were more likely to report
      drink-driving than girls (28 per cent and 13 per cent respectively). Having been
      in trouble with police ranged from 32 per cent for girls recruited by letter to
      75 per cent for boys recruited opportunistically. A high proportion of girls
      reported sexual abuse (34 per cent of the 'letter' group and 41 per cent of the
      'opportunistic' group). Overall, 87 per cent of respondents had used health
      services in the previous year. The results indicate that this is a disadvantaged
      group of young people who are an important target for health service provision
      and interventions.

PMID- 9161074
TI  - Sex, alcohol and drugs? Young people's experience of Schoolies Week.
AB  - The 'Schoolies Week' phenomenon attracts more than 10,000 school leavers to
      Surfers Paradise in November and December each year. In a survey of these young
      people (N = 1796), from Queensland, New South Wales (NSW), and Victoria, about
      two-thirds of the young men and one-third of the young women expected to have
      sexual intercourse while in Surfers Paradise. Of these, about 80 per cent
      expected to use condoms. Most expected to be drunk most nights or every night of
      their holidays and 27 per cent of young men and 17 per cent of young women
      expected to be 'stoned' most nights or every night. Most young men and a
      significant proportion of young women achieved these expectations, with
      respondents from NSW and Victoria being more likely to do so than Queensland
      residents. Over one-third of the sample had engaged in sexual intercourse prior
      to interview, and of these, two-thirds of young men and over half the young women
      always used condoms with casual partners. The rates for sexual intercourse with
      regular partners were slightly lower. Those who were inconsistent condom users on
      holiday were likely to have a history of inconsistent condom use and to have
      multiple casual partners and/or regular partners in addition to casual partners.
      It is recommended that the NSW and Victorian governments accept some
      responsibility for the behaviour of young people attending Schoolies Week. A
      coordinated intervention strategy is required because there are significant prior
      indicators of young people's risk practices in Surfers Paradise during Schoolies
      Week.

PMID- 9161075
TI  - A regional profile of suicide in Queensland.
AB  - A regional profile of suicide in Queensland follows on from earlier work which
      failed to find urban-rural differences in suicide rates. Suicide rates were
      higher in the north of the state and lower in the more developed south Rural
      Queensland health regions displayed both the lowest (Darling Downs and Mackay)
      and the highest (Peninsula) suicide rates. Socioeconomic factors correlated with
      these differences in some regions. Suicide rates for Aboriginal and Torres Strait
      Islanders, especially the young, were high, and may have contributed to elevated
      suicide rates in northern Queensland, but the numbers were insufficient to
      account for observed differences.

PMID- 9161076
TI  - New evidence on fluoridation.
AB  - A review of recent scientific literature reveals a consistent pattern of evidence
      -hip fractures, skeletal fluorosis, the effect of fluoride on bone structure,
      fluoride levels in bones and osteosarcomas--pointing to the existence of causal
      mechanisms by which fluoride damages bones. In addition, there is evidence,
      accepted by some eminent dental researchers and at least one leading United
      States proponent of fluoridation, that there is negligible benefit from ingesting
      fluoride, and that any (small) benefit from fluoridation comes from the action of
      fluoride at the surface of the teeth before fluoridated water is swallowed.
      Public health authorities in Australia and New Zealand have appeared reluctant to
      consider openly and frankly the implications of this and earlier scientific
      evidence unfavourable to the continuation of the fluoridation of drinking water
      supplies.

PMID- 9161077
TI  - Accessibility of and client satisfaction with dental services in Melbourne.
AB  - Public dental clinics play an important role in delivering dental services to
      Australian adults on low incomes. Our objective was to compare the accessibility
      of and client satisfaction with the two main types of public dental service
      providers in Victoria and with private practice services. Clients attending the
      Royal Dental Hospital of Melbourne, Northcote Community Health Centre and private
      practices in Melbourne were surveyed. The hospital's clients faced the greatest
      ecological and organisational obstacles, while private clients faced the greatest
      financial and desirability obstacles. Community centre clients faced fewer
      ecological and organisational obstacles than hospital clients, with the exception
      of long waiting times. Private practice clients were more satisfied overall, and
      had better continuity of care. Private practice clients were more satisfied with
      access, availability and convenience than community centre clients, who in turn
      were more satisfied than hospital clients. There was no distinction between
      private practice and hospital clients on satisfaction with 'pain and treatment',
      but community centre clients were less satisfied. There was no significant
      difference between client group evaluations of interaction with the dentist.
      Regardless of the effects of the Commonwealth Dental Health Program, distinctions
      between various service types and public clinic types are likely to remain,
      because of their different settings. The contrast between a central hospital and
      a community health centre, in terms of the ecological and organisational
      obstacles to care, points to the advantages of putting dental services close to
      the communities they serve.

PMID- 9161078
TI  - Breast cancer five-year survival in New South Wales women, 1972 to 1991.
AB  - This study of breast cancer survival is based on analysis of five-year relative
      survival of 38,362 cases of invasive breast cancer in New South Wales (NSW)
      women, incident between 1972 and 1991, with follow-up to 1992, using data from
      the population-based NSW Central Cancer Registry. Survival was ascertained by
      matching the registry file of breast cancers against NSW death certificates from
      1972 to 1992, mainly by automated probabilistic linkage. Absolute survival of
      cases was compared with expected survival of age- and period-matched NSW women.
      Proportional hazard regression analysis was used for examination of the effects
      on excess mortality of age, period of diagnosis and degree of spread at
      diagnosis. Relative survival at five years increased from 70 per cent in 1972
      1976 to 77 per cent in 1987-1991. Survival improved during the 1970s and in the
      late 1980s. Regression analysis suggested that part of the improved survival in
      the late 1980s was due to lesser degree of spread at diagnosis, whereas the
      improved survival during the 1970s may have been due to treatment. Survival was
      better for those aged 40-49 years (RR = 0.86) and worse for those aged > or = 70
      years (RR = 1.22) compared with the referent group (60-69 years). Excess
      mortality was much less for those with invasive localised disease than those with
      regional spread (RR = 3.1) or metastatic cancer (RR = 15.5) at diagnosis. For the
      most recent period (1987-1991), relative five-year survival was 90, 70 and 18 per
      cent, respectively, for the three degree-of-spread categories.

PMID- 9161079
TI  - Breast cancer five-year survival, by New South Wales regions, 1980 to 1991.
AB  - Breast cancer five-year relative survival was calculated for 16 urban and rural
      regions in New South Wales (NSW) for cases incidents in 1980-1991. Survival
      analysis employed cancer registry data linked with the death register, and age-
      and period-matched regional mortality of NSW women. Proportional hazard
      regression analysis was used to compare excess mortality in breast cancer cases
      in each region. The effect of region was significant (P < 0.05) in analysis,
      after age and the follow-up variable (and their interaction) were adjusted for,
      although no region was significantly different from the referent group (chosen
      because of average relative five-year survival). When degree of spread and its
      interactions were entered into the model, the effect of region became
      nonsignificant. A significant linear trend (P < 0.05) in the adjusted relative
      risk for excess mortality in breast cancer cases was noted when regions were
      divided into quartiles based on socioeconomic status, with higher relative risk
      in low-socioeconomic-status groups; this effect also disappeared with adjustment
      for degree of spread at diagnosis. There was no general effect of rurality versus
      capital city or other metropolitan centres. This study demonstrates a small
      effect of region of residence and implied socioeconomic status on breast cancer
      survival in NSW women, but this becomes nonsignificant when the data are adjusted
      for degree of spread at diagnosis. This suggests that earlier diagnosis would be
      of benefit in reducing minor inequalities in breast cancer survival in NSW women.

PMID- 9161080
TI  - Help-seeking in Vietnam veterans: post-traumatic stress disorder and other
      predictors.
AB  - This study investigated factors predicting help-seeking from the Department of
      Veterans' Affairs (DVA) by Vietnam veterans. Data used were from a national
      Australian survey of Vietnam veterans' health (n = 641) conducted between July
      1990 and April 1993. The survey involved current clinical assessments and
      retrospective questionnaires, supplemented with health and service records
      retrieved from the DVA and Army personnel files. Measures included the 1989-90
      Australian Bureau of Statistics Health Survey questionnaire, and mental health,
      sociodemographic and operational deployment history questionnaires. For both
      current and lifetime diagnoses of post-traumatic stress disorder, a third of the
      veterans with the disorder had never obtained any health care entitlement from
      the DVA. Other than physical and mental problems, which accounted for the
      greatest proportion of the help-seeking odds, significant factors predicting help
      seeking included factors such as: predeployment personality, combat exposure, the
      veterans' own attitudes towards their deployment, experiences during deployment,
      experiences during repatriation and membership of ex-service organisations. These
      findings on how post-traumatic stress disorder and other health problems relate
      to help-seeking patterns could help in developing prevention and care programs
      for stress disorder.

PMID- 9161081
TI  - The health of Filipinas in the Hunter region.
AB  - An interview survey found life-style behaviours (including risk factors and
      screening), social support and psychological health (GHQ-12) among a sample of
      198 Filipina-Australians to be conducive to good health. Knowledge of local
      health services was good, and most women expressed general satisfaction with all
      aspects of life in Australia, except in the area of employment prospects. Despite
      these indications of good health in the group, there remains a need for health
      service providers to be aware of the difficulties faced by a proportion of
      Filipina migrants to Australia.

PMID- 9161082
TI  - Bitten by the travel bug.

PMID- 9161083
TI  - Validation of hepatitis B surveillance data.

PMID- 9161084
TI  - Disadvantage, and the cost of food.

PMID- 9161085
TI  - A review of health effects of aircraft noise.
AB  - Social surveys have established dose-response relationships between aircraft
      noise and annoyance, with a number of psychological symptoms being positively
      related to annoyance. Evidence that exposure to aircraft noise is associated with
      higher psychiatric hospital admission rates is mixed. Some evidence exists of an
      association between aircraft noise exposure and use of psychotropic medications.
      People with a pre-existing psychological or psychiatric condition may be more
      susceptible to the effects or exposure to aircraft noise. Aircraft noise can
      produce effects on electroencephalogram sleep patterns and cause wakefulness and
      difficult in sleeping. Attendances at general practitioners, self-reported health
      problems and use of medications, have been associated with exposure to aircraft
      noise, but some findings are inconsistent. Some association between aircraft
      noise exposure and elevated mean blood pressure has been observed in cross
      sectional studies of schoolchildren, but with little confirmation from cohort
      studies. There is no convincing evidence to suggest that all-cause or cause
      specific mortality is increased by exposure to aircraft noise. There is no strong
      evidence that aircraft noise has significant perinatal effects. Using the World
      Health Organization definition of health, which includes positive mental and
      social wellbeing, aircraft noise is responsible for considerable ill-health.
      However, population-based studies have not found strong evidence that people
      living near or under aircraft flight paths suffer higher rates of clinical
      morbidity or mortality as a consequence of exposure to aircraft noise. A dearth
      of high quality studies in this area precludes drawing substantive conclusions.

PMID- 9161086
TI  - Partners Healthcare System Nursing Informatics Fellowship Program.

PMID- 9161087
TI  - Partnerships for health care practice information.

PMID- 9161088
TI  - Update on virtual nursing informatics organizations.

PMID- 9161089
TI  - Developing and testing a prototype patients care database.
AB  - The purpose of the two pilot studies described in this article was to develop and
      evaluate a database for managing patient care information. A retrospective review
      of medical records for 67 patients was used for capturing nursing information.
      Three categories of data were obtained: (1) patient problems, (2) nursing
      interventions, and (3) patient outcome achievement. A total of 439 patient
      problems was identified. A total of 4541 discrete nursing interventions were
      coded, with assessment and surveillance activities accounting for 26% of the
      total. The degree to which targeted patient outcomes were achieved was assessed
      by analyzing documentation of patient outcomes in the medical record. Of 2326
      expected patient outcomes identified, only 55% (1272) were documented as "met" in
      the medical records. Potential uses for the database include outlier analysis and
      outcomes assessment in specific patient populations.

PMID- 9161090
TI  - Increasing the effectiveness and efficiency of academic advising through
      computerization.
AB  - Academic advising is an essential part of any university degree program and
      becomes especially important in programs where there is competitive and limited
      admission to professional courses. This requires that academic advisors have
      ready access to student scholastic and demographic data for counseling and
      statistical purposes. The use of computers in creating a database for student
      records has become routine in most universities and colleges. Computerization of
      these records through the registration process creates a university database with
      the potential for many different applications. This article describes the
      development of a computer software program for a baccalaureate science of nursing
      program that makes use of a university's database to provide the foundation of a
      computer software program used in the nursing academic advising office.
      Identifying the special needs and requirements of the nursing advising program
      and developing a close working relationship with the computer programmer were
      essential in the development and implementation process. The result was an
      increase in the effectiveness and efficiency of the advising process, better
      record keeping, and better use of available student data for statistical
      purposes.

PMID- 9161091
TI  - Technology assessment. A framework for generating questions useful in evaluating
      nursing information systems.
AB  - Nursing information systems are computer systems that enable nurses to collect,
      manipulate, store, retrieve, display, and communicate data to administer nursing
      services and resources, manage nursing practice to improve patient care, and
      advance nursing knowledge. Selection and implementation of a nursing information
      system require a clear vision of the need for the system, careful planning, and
      astute forward thinking. Technology assessment provides a framework for
      generating pragmatic questions that can be used in systematically evaluating
      nursing information systems. This article provides a brief overview of nursing
      information systems, explains the technology assessment framework, and gives
      examples of questions useful in evaluating a nursing information system.

PMID- 9161092
TI  - Health services organizations computer innovation. Ready or not?
AB  - Health services organizations (HSOs) have expanded into increasingly integrated
      delivery systems requiring more sophisticated health information systems (HISs)
      to support decision making. Computer innovations are required in most HSOs to
      support these HISs. Health services organizations decision makers are faced with
      many complex decisions during the computer innovation process. One of their most
      important decisions is judging HSO innovation readiness. Accurate judgments about
      HSO innovation readiness will have a direct impact on how successful decision
      makers are as computer innovators.

PMID- 9161093
TI  - Interactive videodisc instruction is an alternative method for learning and
      performing a critical nursing skill.
AB  - A study was conducted to compare the effectiveness of interactive videodisc
      instruction (IVDI) with the traditional lecture/demonstration as an alternative
      method for learning and performing a critical nursing skill. Students were
      assigned randomly to a treatment group that worked in small groups to complete
      the IVDI on intravenous therapy skills and a control group receiving the same
      content in a classroom lecture/demonstration format. After the instruction, each
      subject performed a re-demonstration of the learned skills using specific
      guidelines. Results revealed that although the IVDI group scored higher on the
      overall re-demonstration, there was no significant difference in the ability of
      the two groups to effectively perform this critical nursing skill. These findings
      support the use of IVDI as an alternative self-paced, independent study method
      for learning psychomotor skills and are consistent with previous studies, which
      indicate that working in small groups on the computer has a positive effect on
      self-efficacy and achievement.

PMID- 9161094
TI  - Immunohistochemical study of myelin-specific proteins in pt rabbits.
AB  - The cellular/regional expression of myelin-specific proteins: PLP, MBP, CNP-ase,
      MAG and MOG was investigated in the brains of 14 and 42 days old control and pt
      mutant rabbits. The results showed severe reduction in expression of PLP protein,
      the known molecular target of pt mutation. The minor differences in
      immunostaining of the other studied myelin-connected proteins between normal and
      mutant rabbits confirmed once more the deficient and delayed myelination in pt
      brain. No signs of the increased retention of neither PLP nor any other protein
      in pt oligodendrocytes were evidenced in this study.

PMID- 9161095
TI  - Intracellular calcium overload in a model of quinolinic acid neurotoxicity in
      organotypic culture of rat hippocampus; inhibited by nimodipine.
AB  - The ultrastructural studies of intracellular calcium localization were performed
      in a model of quinolinic acid (QUIN) neurotoxicity in vitro. The calcium overload
      was investigated in organotypic culture of rat hippocampus exposed to QUIN or
      treated simultaneously with QUIN plus calcium channels blocker-nimodipine. For
      electron microscopy, the cultures were processed using the oxalate-pyroantimonate
      cytochemical technique in order to visualize the electron-dense calcium
      pyroantimonate granules. QUIN application induced massive accumulation of calcium
      deposits in damaged mitochondria of degenerating pyramidal neurons and swollen
      postsynaptic dendrites. Nimodipine exerted the potent neuroprotective effect
      against QUIN neurotoxicity accompanied by significant inhibition of intracellular
      calcium accumulation. However, in the glial cells, the presence of calcium
      precipitates was found both in the cultures exposed to QUIN alone and in those
      treated simultaneously with QUIN plus nimodipine. The present studies support the
      concept of calcium contribution in excitotoxic neuronal damage and suggest the
      significant role of calcium channel blockers in prevention of QUIN-induced
      mitochondrial calcium overload.

PMID- 9161096
TI  - Ultrastructure of myelinated fibers of sciatic nerve in acute vincristine
      intoxication.
AB  - Numerous clinical reports documented that in some patients vincristine (VCR) may
      cause a risk for life (stridor) and painful symptoms of acute intoxication. The
      present study was undertaken to examine ultrastructural changes in the sciatic
      nerve of rabbits following acute vincristine intoxication. Our results show, that
      in a few hours, some axons of this nerve may undergo degeneration and atrophy.
      These changes were initially followed by the cleavage of adaxonal myelin sheets,
      that spontaneously formed concentric scrolls and tangled threads. Finally, myelin
      sheath collapsed around the atrophied axon. The results provide evidence that
      acute VCR intoxication primarily affects the axons. Myelin changes are caused by
      the loss of supportive role of atrophied axon for the myelin sheath. The effect
      of intoxicated Schwann cells on the myelin in acute VCR intoxication is not clear
      and requires further study.

PMID- 9161098
TI  - A morphometric evaluation of morphological types of microglia and astroglia in
      human fetal mesencephalon.
AB  - Quantitative changes associated with the differentiation of microglial and
      astroglial cells in 48 fetal mesencephalons between 8 and 22 week of gestation
      (GW) were studies. Using lectin (RCA-1) labelling, two morphological types of RCA
      1 positive cells, ameboid microglia (AM) and ramified microglia (RM) were
      identified on the basis of the cell body shape and the configuration of
      cytoplasmic processes. Astrocytes (AS) were identified by immunocytochemical
      labelling of GFAP. Measurements of microglial and astroglial cells were carried
      out in mesencephalon tectum and tegmentum under the microscope in sequential
      segments corresponding to equal sized non-overlapping areas. The quantitative
      data about concerning the number and percentage distribution of AM, RM and AS
      from each of the grid-quartiles were analyzed. The study revealed a time-sequence
      of appearance, characteristic pattern of distribution along perpendicular and
      longitudinal axes originating from aqueduct and changes in percent distribution
      of both types of microglial cells and astrocytes. Ameboid type of microglia was
      already present in 8 GW fetus in tectum (22.5 cells/mm2) and in tegmentum (10.2
      cells/mm2). During the fetal development the number of AM peaked about 8-9 GW in
      tectum, accounting for 29 cells/mm2 close to aqueduct, and about 11-12 weeks in
      tegmentum, reaching 10.2-11 cells/mm2 close to aqueduct. As the fetus development
      advanced, the number of AM cells both in tectum and tegmentum was slowly dropped
      down reaching about 1.0 cells/mm2 in 20-22 GW. The ramified microglial cells as
      well as astroglial cells emerged in the fetal mesencephalon after 11 GW. A
      quantitative study also revealed a rapid increase in the density of RM in 13-16
      GW (6.3 cells/mm2-close to aqueduct) and AS cells in 13-16 GW (36 cells/mm2-close
      to aqueduct) and later a decrease in cell number was observed. Similarly to AM,
      changes in the number of RM and AS cells were stabilized to about 20-22 GW. The
      percentage distribution of each type of microglia and astrocyte cells both in
      tectum and tegmentum differed markedly during the fetus development depending on
      the localization along the axes.

PMID- 9161097
TI  - Paraneoplastic syndrome simulating encephalitis in the course of testicular
      seminoma.
AB  - A case of paraneoplastic syndrome diagnosed post mortem in a 68-year-old man with
      a single submandibular lymphatic metastasis of testicular seminoma is presented.
      The syndrome developed 3 years after orchidectomy and clinically combined the
      features of limbic and bulbar encephalitis together with signs of cerebellar
      degeneration. Histological examination revealed marked loss of cerebellar
      Purkinje and granular cells and to a lesser extent of cerebral cortical neurons.
      Additionally axonal injury (spheroids) and multifocal demyelination with sparse
      lymphocytic infiltrations was observed. Immunohistochemically, strong reaction
      with monoclonal anti-human IgG in some neurons of cerebellum was detected whereas
      the reaction with anti-complement (C3b) receptor in corresponding sections was
      negative. It is suggested that the presented case may represent a "burn out"
      stage of paraneoplastic syndrome associated with anti-neuronal antibodies,
      however the isolation of specific antibodies was not performed.

PMID- 9161099
TI  - Endothelin-like immunoreactivity in hippocampus following transient global
      cerebral ischemia. I. Neuronal and glial cells.
AB  - The effect of transient, global ischemia on endothelin (ET) localization in CA1
      area of hippocampus of the rats was investigated using post-embedding immunogold
      method. This paper provides immunocytochemical evidence that cerebral ischemia is
      accompanied by the increase of production of endothelin in CA1 area of the rat.
      This study focuses on the analysis ET-like immunoreactive neurons and glial cells
      in hippocampal CA1 area after long-term survival after ischemia: 1 week-12
      months. One and two weeks after ischemia appearance of shrunken neurons and
      significant increase in ET-like immunoreactivity in astroglial cells as well as
      their proliferation was observed. Six and twelve months--marked immunoreactivity
      of endothelin in shrunken neurons and in perineuronal microglial macrophages was
      observed. The data suggest the possibility that the increased intracellular
      content of endothelin has a role in the development of neuronal death even
      following a long-term period after ischemia.

PMID- 9161100
TI  - Endothelin-like immunoreactivity in hippocampus following transient global
      cerebral ischemia. II. The blood-brain interphase.
AB  - The effect of transient, global cerebral ischemia on the distribution of
      endothelin (ET) in blood-brain barrier (BBB) in CA1 area of hippocampus long-time
      after ischemia was estimated using post-embedding immunogold technique. ET-like
      immunoreactivity as a gold particles was localized in all compartments of the
      blood-brain barrier e.g. in endothelial cells, in pericytes, in periendothelial
      space including basement membrane, and in astroglial processes. In control animal
      the density of labelling in all elements of BBB in CA1 area of hippocampus was
      moderate. ET-like immunoreactivity (ET-like IR) was estimated 1 week-12 months
      after ischemia. Intense ET-like IR in all elements of BBB was noted 2 and 6
      months after ischemia. A potential pathophysiological role of endothelin in
      cerebral vasospasm in long-time after ischemia is well documented.

PMID- 9161101
TI  - Comparative anatomy of arterial vascularization of the rhinencephalon in man, cat
      and sheep.
AB  - The aim of this study was anatomical and comparative examination of arterial
      vascularization of the rhinencephalon in man and in macrosmatic mammals. The
      studies were performed by the own injection method on 27 human brains and 27
      animal ones. The cerebral arteries were injected with synthetic colored latex and
      then prepared in an operating microscope. It was found, that the structure,
      topography and vascular areas of arteries supplying the rhinencephalon in man and
      animals are different. Contrary to the human rhinencephalon, strongly developed
      rhinencephalon in cat and sheep possess its own separate arterial pattern
      composed of special arteries for each regions of paleocortex, supplying the
      olfactory bulb and lobe. In the cat and sheep brains, the region corresponding to
      the human anterior perforated substance comprises the greater rhinencephalon
      surface. It includes the olfactory tubercle and sulcus between the olfactory and
      pyriform lobes. Extracerebral segments of the internal arterioles of the anterior
      and middle cerebral arteries in man and animals have different topography and
      courses. In the human brain, the studied arterioles originate from the maternal
      arteries with singular trunks or vascular pedicles and then enter directly the
      anterior perforated substance. In the cat and sheep brain they derive in two
      forms: as trunks divided into cortical branches of the olfactory lobe running on
      the olfactory tubercle surface and penetrating it, as well as singular trunks
      that enter the brain just over the maternal arteries. In contrary to the
      extracerebral segments of the anterior perforating arteries in man, analogical
      arterioles in the cat and sheep brains form numerous anastomoses. Thus, they
      create anatomical conditions for collateral circulation.

PMID- 9161102
TI  - Visual attention in children with prenatal cocaine exposure.
AB  - Previous studies have reported that developmental disruption of dopaminergic
      systems results in lateralized deficits in visual attention (Posner et al., 1991;
      Craft et al., 1992). Infants who were prenatally exposed to cocaine were
      hypothesized to have increased reaction times to targets in the right visual
      field on measures of visual attention compared with infants who were not exposed
      to cocaine. Seventeen children without prenatal exposure to cocaine and 14
      children who were exposed to cocaine (age range from 8-40 months) completed a
      visual attention task, the Mental Development Index of the Bayley Scales of
      Infant Development, Second Edition; and the Preschool Language Scale, Third
      Edition. Cocaine-exposed children were slower to orient to stimuli in the right
      visual field after repeated trials, especially after attention was first cued to
      the left visual field. They were also less likely to orient to the right when
      given a choice. Results suggest that the left hemisphere visual attention system
      is disproportionately affected by prenatal exposure to cocaine.

PMID- 9161103
TI  - Autobiographical memory in multiple sclerosis.
AB  - Studies have consistently found that patients with multiple sclerosis (MS) are
      impaired on tests of anterograde memory, but the status of remote memory in MS
      remains unclear. To better understand remote memory in MS we administered the
      Autobiographical Memory Interview (AMI) to 44 MS patients and 19 normal controls
      matched for age, education, and gender. Additionally, a shortened version of the
      Famous Faces Test, a test of recall of past U.S. presidents, and a 14-word
      learning list were administered. Patients performed significantly lower than
      controls on the learning list and Famous Faces Test, but not on recall of past
      presidents. On the AMI, patients were significantly impaired on recall of
      semantic but not of episodic memories. These results indicate that MS patients
      exhibit retrograde amnesia that cannot be attributed to anterograde memory
      deficits or lack of exposure to task-relevant information.

PMID- 9161105
TI  - The abstraction of numerical relations: a role for the right hemisphere in
      arithmetic?
AB  - Arithmetical reasoning ability has been investigated in a group study of patients
      with unilateral cerebral lesions. Two series of 38 and 39 patients, who had
      suffered unilateral cerebral lesions of the right and left cerebral hemisphere,
      respectively, were investigated. They completed a neuropsychological battery that
      included a test of computation (Graded Difficulty Arithmetic, GDA; Jackson &
      Warrington, 1986), and a new test of numerical series completion (Arithmetical
      Reasoning Test, ART). Whereas the left-hemisphere lesion group were markedly more
      impaired on the GDA compared to both the right-hemisphere lesion group and a
      standardization sample, both lesion groups were equally severely impaired on the
      ART. It is suggested that the abstraction of numerical relations, which is
      essential to numerical series completion, relies on the integrity of the right
      hemisphere. A global model of arithmetic processing that incorporates these
      findings is proposed.

PMID- 9161104
TI  - Predictors of intellectual performance in adults with intractable temporal lobe
      epilepsy.
AB  - The relationships of medical, developmental, social, and familial variables to
      intellectual performances (IQ scores) were assessed in a sample of 242 adult
      patients with intractable lateralized temporal lobe epilepsy. Lower IQ scores
      were associated with low patient and parent education. In addition to the
      significant contributions of nonneurological social and familial factors to IQ,
      early age at onset of regular seizures and presence of primary neurological
      dysfunction in the left cerebral hemisphere were also both independently related
      to lower IQ. The obtained results suggest that the occurrence of regular seizures
      during a critical period in early childhood neural maturation poses the greatest
      risk to cognitive development in the epilepsy population. Total duration of
      seizures, history of severe convulsive episodes, and the occurrence of another
      nonepileptic neurological problem in early childhood do not contribute
      significantly to delayed cognitive development.

PMID- 9161106
TI  - Neuropsychological performance of journeymen painters under acute solvent
      exposure and exposure-free conditions.
AB  - Journeymen painters were evaluated with a comprehensive battery of
      neuropsychological tests and compared to demographically similar nonexposed
      controls. For painters, a cumulative exposure to solvents was estimated from a
      structured interview that derived an index based on lifetime exposure and
      exposure in the past year. Painters were tested either shortly after having
      painted or after an exposure-free interval. Significant between-group differences
      were found on a cluster of tests measuring learning and memory. Within the
      painter group, scores on the learning and memory tests were significantly related
      to the interaction of condition and exposure. That is, those painters who were
      tested soon after painting and who also had a higher overall lifetime exposure,
      performed worst on tests of learning and memory. These results are consistent
      with the view that neuropsychological function--particularly learning and memory-
      may be compromised in active workers with a history of chronic solvent exposure.
      Furthermore, both the chronicity of solvent exposure, as well as the acuteness of
      the exposure, are significant factors in cognitive performance.

PMID- 9161108
TI  - The neuropsychology of object constancy.
AB  - There have been several proposals for the mechanism by which we are able to
      recognize an object across a number of viewpoints. Viewpoint-dependent accounts
      suggest that recognition may be based on an incremental transformation (e.g.,
      mental rotation) strategy, while a variety of viewpoint-independent mechanisms
      for object recognition have also been proposed. Recent research in neurobiology,
      based on the two cortical visual systems account, suggest that the processes of
      viewpoint-dependent and viewpoint-independent object recognition may rely on
      separate anatomical regions, and that brain lesions may leave patients with
      selective access to particular types of representation. Evidence from a variety
      of neuropsychological disorders are reviewed to support the position that
      viewpoint-independent object recognition depends upon the integrity of
      occipitotemporal structures. In addition, it is suggested that viewpoint
      dependent processes (perhaps depending on occipitoparietal structures) may
      supplement this primary system under nonoptimal circumstances.

PMID- 9161107
TI  - Brain atrophy in HIV infection is more strongly associated with CDC clinical
      stage than with cognitive impairment.
AB  - HIV infection often results in MRI-detectable brain atrophy and white matter
      signal hyperintensities (WMSHs). Magnetic resonance images were obtained from 31
      HIV+ male patients and 10 high-risk controls. Variation within the HIV+ group on
      neuropsychological (NP) impairment and stage of systemic disease were relatively
      independent, allowing examination of the relative association of MRI measures
      with NP impairment versus with systemic stage of disease. HIV+ patients compared
      to high-risk controls evidenced global atrophy, reduced caudate nuclei volume,
      and a trend to gray matter volume loss but no difference in white matter volume
      or in WMSHs. These effects were progressive with CDC clinical stage such that
      patients at CDC stage A had values very close to those of controls, while
      patients at CDC stage C had the most abnormal values. In contrast, the
      relationship between these MRI variables and severity of NP impairment was much
      less dramatic, with the mildly to moderately impaired HIV+ subjects showing MRI
      volume effects greater than or equal to those of the severely impaired HIV+
      subjects. These results suggest that MRI-detectable brain atrophy secondary to
      HIV infection is not the primary substrate underlying the progressive NP
      impairment in HIV disease.

PMID- 9161109
TI  - Modification of the EORTC QLQ-C30 (version 2.0) based on content validity and
      reliability testing in large samples of patients with cancer. The Study Group on
      Quality of Life of the EORTC and the Symptom Control and Quality of Life
      Committees of the NCI of Canada Clinical Trials Group.
AB  - A revision of the Quality of Life Questionnaire (QLQ-C30) of the European
      Organization for Research and Treatment of Cancer (EORTC) was undertaken to
      improve low internal consistency estimates (Cronbach's alpha) and content
      validity for the role functioning scale and a conceptual difficulty (undue
      emphasis on physical functioning) in the global quality of life (QOL) scale. The
      role functioning items were reworded and a four-category response format was
      substituted for the previous dichotomous format. A new item asking about 'overall
      health' was substituted for the 'overall physical condition' item in the global
      QOL domain. The original and new versions were tested at three time points in a
      total of 1,181 patients with cancer in Canada (n = 696) and the Netherlands (n =
      485). In both samples there was a marked improvement in internal consistency for
      the role functioning scale (Cronbach's alpha s ranging from 0.78-0.88) in the new
      version. In the global QOL scale, the substitution of the new item for the
      previous one did not alter internal consistency (Cronbach's alpha's ranging from
      0.81-0.92). The revised versions of the role functioning and global QOL domains
      have been incorporated into the QLQ-C30 (version 2.0).

PMID- 9161110
TI  - Sample sizes for randomized trials measuring quality of life in cancer patients.
AB  - This paper describes the methods appropriate for calculating sample sizes for
      clinical trials assessing quality of life (QOL). An example from a randomized
      trial of patients with small cell lung cancer completing the Hospital Anxiety and
      Depression Scale (HADS) is used for illustration. Sample size estimates
      calculated assuming that the data are either of the Normal form or binary are
      compared to estimates derived using an ordered categorical approach. In our
      example, since the data are very skewed, the Normal and binary approaches are
      shown to be unsatisfactory: binary methods may lead to substantial over estimates
      of sample size and Normal methods take no account of the asymmetric nature of the
      distribution. When summarizing normative data for QOL scores the frequency
      distributions should always be given so that one can assess if non-parametric
      methods should be used for sample size calculations and analysis. Further work is
      needed to discover what changes in QOL scores represent clinical importance for
      health technology interventions.

PMID- 9161111
TI  - The relationship between personality and quality of life in persons with
      schizoaffective disorder and schizophrenia.
AB  - The goal of this study was to examine the effects of personality traits as
      measured by the NEO-PI on the quality of life (QOL) of persons with
      schizoaffective disorder and schizophrenia. The premise of this research is that
      personality traits may be important in shaping one's outlook and satisfaction
      with life. In a prior pilot study, personality traits were measured in persons
      with schizoaffective disorder and schizophrenia. In this study, the relationship
      between QOL and specific personality domains as assessed by the NEO-PI were
      studied in 21 patients. Global QOL as measured by the Lehman QOL instrument was
      positively correlated with Extroversion (E) and Agreeableness (A), and negatively
      correlated with the domain of Neuroticism (N). Global satisfaction scores were
      not correlated with ratings of psychoticism, paranoia or depression. These data
      suggest that even in psychotic conditions such as schizoaffective disorder or
      schizophrenia, intrapsychic factors influence one's sense of QOL. In addition,
      these data suggest that personality variables may differentially affect patients'
      satisfaction and QOL with different treatment settings.

PMID- 9161112
TI  - Development of a health-related quality of life instrument for use in children
      with spina bifida.
AB  - The objective of this study was to develop a spina bifida health-related quality
      of life (HRQOL) instrument. Items were generated through semistructured
      interviews, and reduced by frequency-importance product ranking. Validity was
      assessed by correlating the HRQOL score with a global question concerning the
      child's well-being using the Spearman's rank coefficient, and the Piers-Harris
      Children's Self-Concept Scale (P-H) using the Pearson correlation coefficient.
      Reproducibility was assessed at 2-week intervals using the intra-class
      correlation coefficient (ICC). Field testing was undertaken in a larger sample to
      evaluate item-total correlation, internal consistency and construct validity.
      Patients taking part in the study were 329 children and adolescents with spina
      bifida attending two treatment centres. Over 600 items were generated. These were
      reduced to 47 questions and 50 questions, for children and adolescents
      respectively. The correlation between the HRQOL score and the global question was
      r = 0.57, and with the P-H was 0.26 (children). These values for adolescents were
      0.63, and 0.89, respectively. Reproducibility was ICC = 0.78 (children) and 0.96
      (adolescents). Following field testing, the questionnaire was further reduced to
      44 questions (children) and 47 questions (adolescents) by eliminating questions
      with an item- total correlation less than 0.20. Cronbach's alphas for the final
      instrument were 0.93 (children) and 0.94 (adolescents), and construct validity
      correlations were 0.63 (children) and 0.37 (adolescents). The spina bifida HRQOL
      instrument has good measurement properties and may be used as a discriminative
      instrument. Assessment of responsiveness is necessary before using it to evaluate
      therapy in clinical trials.

PMID- 9161113
TI  - A comparison of time trade-off and quality of life measures in patients with
      advanced cancer.
AB  - Quality of life (QOL) measures are now accepted as indicators of efficacy in the
      palliative treatment of cancer. Utility measures may also provide valuable
      information in this area yet they have rarely been applied. To assess the
      concordance of QOL and utility scales, 93 patients with advanced, symptomatic
      cancer completed two QOL instruments, the Spitzer Quality of Life Index (QLI) and
      Spitzer Uniscale, and a time-trade off (TTO) question reflecting the utility of
      their health states. The scales were self-administered. All patients completed
      the QLI and Uniscale but only 37% of participants were prepared to trade time.
      The remainder comprised 39% who felt too well to trade time and 24% who did not
      wish to consider trading time at all. Those prepared to trade time had
      significantly worse scores on both QLI and Uniscale instruments than those who
      felt too well to trade. However the correlation between time traded and QLI and
      Uniscale scores was poor. We conclude that the TTO question used in this study,
      while not strongly related to QOL, provides a measure of the patient's attitude
      to their health state. This may explain why patients differ in their attitude to
      quantity vs. quality of life.

PMID- 9161114
TI  - Factor analysis, causal indicators and quality of life.
AB  - Exploratory factor analysis (EFA) remains one of the standard and most widely
      used methods for demonstrating construct validity of new instruments. However,
      the model for EFA makes assumptions which may not be applicable to all quality of
      life (QOL) instruments, and as a consequence the results from EFA may be
      misleading. In particular, EFA assumes that the underlying construct of QOL (and
      any postulated subscales or 'factors') may be regarded as being reflected by the
      items in those factors or subscales. QOL instruments, however, frequently contain
      items such as diseases, symptoms or treatment side effects, which are 'causal
      indicators'. These items may cause reduction in QOL for those patients
      experiencing them, but the reverse relationship need not apply: not all patients
      with a poor QOL need be experiencing the same set of symptoms. Thus a high level
      of a symptom item may imply that a patient's QOL is likely to be poor, but a poor
      level of QOL need not imply that the patient probably suffers from that symptom.
      This is the reverse of the common EFA model, in which it is implicitly assumed
      that changes in QOL and any subscales 'cause' or are likely to be reflected by
      corresponding changes in all their constituent items; thus the items in EFA are
      called 'effect indicators.' Furthermore, disease-related clusters of symptoms, or
      treatment-induced side-effects, may result in different studies finding different
      sets of items being highly correlated; for example, a study involving lung cancer
      patients receiving surgery and chemotherapy might find one set of highly
      correlated symptoms, whilst prostate cancer patients receiving hormone therapy
      would have a very different symptom correlation structure. Since EFA is based
      upon analyzing the correlation matrix and assuming all items to be effect
      indicators, it will extract factors representing consequences of the disease or
      treatment. These factors are likely to vary between different patient subgroups,
      according to the mode of treatment or the disease type and stage. Such factors
      contain little information about the relationship between the items and any
      underlying QOL constructs. Factor analysis is largely irrelevant as a method of
      scale validation for those QOL instruments that contain causal indicators, and
      should only be used with items which are effect indicators.

PMID- 9161115
TI  - Quality of life scores: an independent prognostic variable in a general
      population of cancer patients receiving chemotherapy. The National Cancer
      Institute of Canada Clinical Trials Group.
AB  - This report examines the prognostic associations between QOL scores measured by
      the EORTC QLQ-C30 and survival in a large heterogeneous population of cancer
      patients. Eight hundred and fifty-one cancer patients who were to receive
      chemotherapy were enrolled in two National Cancer Institute of Canada Clinical
      Trials Group (NCIC CTG) antiemetic trials. All patients completed the EORTC QLQ
      C30 immediately prior to their first chemotherapy. Survival data were available
      and obtained for 474 of 639 patients (74%). Cox's proportional hazards model was
      used to assess the independent impact of QOL and demographic variables on
      survival. Presence of metastatic disease, diagnosis of lung or ovarian cancer,
      ECOG performance status, global quality of life and emotional functioning were
      significantly associated with survival. Global QOL was predictive in all
      patients, in subgroups of patients with metastatic disease, with breast and lung
      cancer and other tumour types. In patients with low global quality of life
      scores, patients with low emotional functioning ratings lived longer than did
      patients with high emotional functioning ratings. Patients with high global QOL
      live significantly longer than do patients with low global QOL. The relationship
      between emotional functioning in patients with low global QOL and survival needs
      confirmation.

PMID- 9161116
TI  - Constructing health state preference values from descriptive quality of life
      outcomes: mission impossible?
AB  - Descriptive quality of life questionnaires are commonly administered in clinical
      trials, to evaluate outcomes from the patient's perspective alongside
      conventional clinical measures. When expressed in single index form as health
      state preference values (HSPVs), quality of life information is also relevant to
      economic evaluations. By combining HSPVs with survival information, quality
      adjusted life years (QALYs) may be derived for cost-utility analysis. Although
      HSPVs are rarely measured prospectively in cancer clinical trials, the UK Medical
      Research Council Cancer Therapy Committee recommends the routine administration
      of two specific quality of life questionnaires: the Rotterdam Symptom Checklist
      and the Hospital Anxiety Depression Scale. This study explores two potential
      methods for secondary derivation of HSPVs from these instruments, using data
      gathered in a clinical trial of two forms of radiotherapy for non-small cell
      cancer of the bronchus. The first method, secondary mapping to existing utility
      scales, was found to be infeasible from the above questionnaires. The second
      method used factor analysis to summarize the descriptive quality of life data
      collected through the questionnaires. This revealed five distinct factors
      prevalent in the trial population. Using these factors, simplified health state
      scenarios were developed from which direct measurement of HSPVs was feasible. As
      the resulting HSPVs and any QALYs that may be derived from them are cancer
      specific, their potential value in informing resource allocation would be limited
      to decisions within oncology services.

PMID- 9161117
TI  - The effect of assessment method and respondent population on utilities elicited
      for Gaucher disease.
AB  - Measured preferences have been reported to vary with the method of elicitation
      and respondent population surveyed. We elicited utilities for Gaucher disease
      using a multimedia implementation of the time trade-off, standard gamble, and a
      conceptually different, largely untested approach, the risk-risk trade-off, from
      those who are healthy, those with a chronic illness and those with Gaucher
      disease. The risk-risk trade-off produced significantly lower utilities than the
      other two preference assessment methods and had the poorest test-retest
      reliability. The respondent's self-rated current health state utility was the
      most important determinant of utility values elicited by the time trade-off and
      standard gamble for the hypothetical health states. Our results do not support
      the use of our implementation of the risk-risk trade-off method. In eliciting
      preferences for hypothetical health states from the general population, the
      subjective rating of a respondent's own health state should be considered in
      determining representative population groups.

PMID- 9161118
TI  - Quality of life claims in trials of anti-hypertensive therapy.
AB  - The increasing use of so-called quality of life assessments in clinical trials
      can be seen as a laudable attempt to gather information about the impact of
      treatment on patients which goes beyond the purely clinical. However, there is a
      growing tendency for pharmaceutical companies to use quality of life claims in
      marketing strategies. The varying protocols and study populations, together with
      multicentre and multicountry trials and the variety of implied definitions of
      quality of life raise serious issues concerning the scientific credibility of
      conclusions about quality of life as an endpoint. This paper reviews reports of
      randomized controlled trials of anti-hypertensive therapy which used 'quality of
      life', assessed by patient-completed questionnaires, as one of the outcome
      variables. Criteria referring to definitions of quality of life, the validity and
      reliability of the measures used, administration procedures, treatment of data,
      adequacy of discussion of alternative explanations of the findings and the
      legitimacy of the findings are spelled out. It is concluded that none of the
      studies reviewed were justified in the claims made concerning differential
      effects of therapies on 'quality of life'.

PMID- 9161119
TI  - Health status prediction in critically ill children: a pilot study introducing
      Standardized Health Ratios.
AB  - Performance of intensive care is usually quantified by means of standardized
      mortality rates, where standardization is directed towards the severity of
      illness on admission. However, as more critically ill patients survive,
      functional outcome and quality of life of these patients becomes more important.
      In a prospective study in a 10-bed tertiary paediatric intensive care unit (ICU),
      admission and follow-up health status were collected for 209 surviving patients.
      For this cohort of patients, health status 1 year after admission was also
      predicted, using the quantified health-utility-index (HUI), as a value between 0
      and 1. For this purpose, two alternative multiple regression models were
      constructed. The most important predictors of 1-year health status were the level
      of sensation, mobility and cognition on admission to which self-care, systolic
      blood pressure, oxygen, Glascow Coma Scale, glucose and age may be added. The two
      alternative predictive models performed equally well (R2 = 0.83 and 0.84
      respectively), indicating that health status could be predicted to a significant
      degree. The concept of relating expected future health status (based on base-line
      health status), with actual (observed) health status is denoted with the
      Standardized Health Ratio (SHR). In combination with the Standardized Mortality
      Ratios (SMR), such a ratio may become a new comprehensive indicator of
      performance in intensive care medicine.

PMID- 9161120
TI  - Chronic fatigue syndrome/myalgic encephalomyelitis as a twentieth-century
      disease: analytic challenges.
AB  - The challenges of chronic fatigue syndrome (often called myalgic
      encephalomyelitis, especially in the UK) (CFS/ME) to analytical and medical
      approaches are connected with our inability to understand its distressing somatic
      symptoms in terms of a single identifiable and understandable disease entity. The
      evidence for the roles of viral aetiologies remains inconclusive, as does our
      understanding of the involvement of the immune system. The history and social
      context of CFS/ME, and its relation to neurasthenia and psychasthenia are
      sketched. A symbolic attitude to the condition may need to be rooted in an
      awareness of psychoid levels of operation, and the expression and spread of
      CFS/ME may sometimes be aided by the ravages of projective identification.
      Psychic denial, sometimes violent, in sufferers (especially children and
      adolescents) and their families may be important in the aetiology of CFS/ME. We
      draw out common threads from psychodynamic work with five cases, four showing
      some symptomatic improvement, analytic discussions of three cases being presented
      elsewhere in this issue of JAP.

PMID- 9161121
TI  - A body with chronic fatigue syndrome as a battleground for the fight to separate
      from the mother.
AB  - I describe the therapy of a 20-year-old women who believed that her difficulties
      in concentrating and remembering were caused by her "ME' (Myalgic
      encephalomyelitis, Chronic fatigue syndrome, or CFS). She had been fathered by a
      man who never left his own wife. Work with her dreams revealed a within-body
      drama in which she was locked in an unspeakable fight to the death with her
      mother. Her symptoms improved after parallels between a dream and an accident
      showed her own self-destructive hand in her story. Another dream, reflecting her
      first 'incestuous' affair, showed her search for her original father-self as
      someone separate from mother, and a later affair provided a between-body drama,
      helping her to own the arrogant and abject traits she had before seen only as her
      mother's. I show how we worked in the area of Winnicott's first 'primitive agony'
      as experienced by a somatizing patient, stuck in a too-close destructive
      relationship with her mother-body. I discuss how analytical work can be done with
      the primitive affects and conflicts against which the ME symptoms may be
      defending.

PMID- 9161122
TI  - Coniunctio--in bodily and psychic modes: dissociation, devitalization and
      integration in a case of chronic fatigue syndrome.
AB  - Three years of analytical psychotherapy with a professional woman in mid-life,
      suffering from chronic fatigue syndrome (CFS), is described. Gradual recovery
      merged into mid-life changes; marriage, along with a new balance of maternal and
      paternal imagos, enabled her to trust enough to become pregnant-coniunctio in the
      most primal bodily and psychic modes. Her life-long, schizoid type pattern, "the
      pendulum of closeness and isolation', with its extreme of psycho-physical
      collapse and devitalization, was replayed in therapy. The analyst's symbolic
      attitude is emphasized, containing the patient's initial affective explosion and
      validating the physicality of her condition. Mirroring and steady rhythmic
      attunement became a new, pre-verbal, source of trust-vitalization;
      differentiation and separation replaced defensive splitting and dissociation.
      Then the overwhelmingly powerful bodily/maternal could be counterbalanced by the
      masculine, and a transitional space emerged for symbolic work. Both the
      regressive and the dynamic aspects of CFS are located in the earliest
      undifferentiated, archetypal, bodily/psychic modes, when the frustration of
      primary needs evokes the defences of the self. It is argued that our
      psychodynamic understanding can contribute to the stalemate in seeing chronic
      fatigue syndrome as either an organic illness or depression, and that a new
      linking of the somatic and psychic calls for a new professional collaboration.

PMID- 9161123
TI  - A view of the violence contained in chronic fatigue syndrome.
AB  - In this paper I ask whether there might be any one particular psychopathology
      likely to be linked specifically with the physical illness known as chronic
      fatigue syndrome (CFS) or myalgic encephalomyelitis (ME), and whether CFS/ME aids
      and abets and "fits' an original mental state. I think the question cannot yet be
      answered. However it is my hypothesis that in some personality structures the
      onset of CFS/ ME following a physical illness exacerbates negativity and is an
      aspect of ordinary depression where there is a lowering of energy levels and a
      loss of zest for life, or it may reveal the pathological aspect of unresolved
      rage. Depending on the degree of pathological disturbance, working with and
      through the rage may or may not result in a resolution of the symptoms of ME. In
      this paper I consider some of the problems in the transference and
      countertransference relationship, which make it extremely difficult to separate
      out reality from phantasy. There is then the further problem of the denial of the
      psyche by the patient as part of the violence inherent in the illness. One case
      is presented, an example of ME in a borderline male patient in whom resolution
      could not be achieved.

PMID- 9161124
TI  - More chaos on the microbiology front: the E. coli O157 outbreaks.

PMID- 9161125
TI  - Antibiotic resistance in the staphylococci.
AB  - There has been much interest in the media, international as well as national, on
      the potential for the development of "superbugs' by which is usually meant
      pathogenic bacteria resistant to all available antibiotics. Two of the genera
      most often thought to fall into this category are the staphylococci (MRSA or
      Methicillin Resistant Staphylococcus aureus) and the enterococci (VRE or
      Vancomycin Resistant Enterococci) and although this article concentrates on the
      staphylococci the two share much in the way of transmissible genes.

PMID- 9161126
TI  - Rinderpest: at war with the disease of war.
AB  - Rinderpest, the legendary cattle plague, has caused devastating losses for
      centuries and remains the biggest threat to sustainable livestock production in
      developing countries. Strenuous efforts are now being made to achieve global
      eradication of this viral disease, a goal made feasible through the use of
      attenuated live vaccines developed in the 1950s. Their use almost resulted in
      eradication in the 1970s but left several foci of disease from where the plague
      then re-emerged. Recent mass vaccination has resulted in the limitation of
      disease to parts of Africa, Pakistan, Afghanistan, the Middle East and India.
      Confirmation of the disease status of the countries has been aided by
      developments in serological techniques through exploitation of monoclonal
      antibodies (in Enzyme Linked Immunosorbent Assay-ELISA) and by advances in
      molecular biology such as in the use of polymerase reaction technologies (PCR).
      This has extended into the development of new recombinant vaccines. It is
      anticipated that eradication will be complete by the year 2010. This would be
      only the second example, after smallpox in man, of the eradication of a viral
      disease. The picture shows a scene of devastation during the Great Rinderpest
      Pandemic of 1889-1897 in South Africa. The disease swept through the African
      continent killing virtually all the cattle and wild ungulates.

PMID- 9161127
TI  - Biodiversity and terrestrial ecosystem processes.

PMID- 9161128
TI  - The use of interactive computed tomography to predict the esthetic and functional
      demands of implant-supported prostheses.
AB  - Diagnosis, treatment planning, and prediction of a final implant-supported
      prosthetic design require precise noninvasive presurgical information. In
      addition, coordination of implant team member services and predetermination of
      treatment fees are critical to a successful resolution of patient needs and
      concerns. By combining the use of a clinically verified barium-coated template
      and interactive computed tomography, the implant team can determine and address
      the relevant issues affecting treatment outcomes. These issues include:
      fixture/prosthesis incompatibility; recognition of anatomic limitations and
      anomalies; the need for presurgical bone augmentation; fixture diameter and
      distribution; abutment type and angle; bone density; soft-tissue augmentation
      requirements; accurate fee determination; and medicolegal protection. The data
      collection methodology and format for the Mecall and Rosenfeld prosthesis
      prediction analysis are discussed as part of a case presentation.

PMID- 9161129
TI  - Teeth or implants: a 1990s dilemma.
AB  - Using endosseous implants to replace missing teeth is a highly predictable
      process when the precepts defined by Branemark are followed. The question of
      whether or not to extract periodontally compromised teeth, however, remains
      controversial. This article presents a case report illustrating some of the
      concerns involved when treating a patient with a combination of natural teeth and
      implants, and proposes several compelling questions regarding the treatment
      decisions made in this case.

PMID- 9161131
TI  - The relationship of the guided gingival frame to the provisional crown for a
      single-implant restoration.
AB  - This article discusses and defines the use of the provisional crown to encourage
      gingival growth to provide an ideal frame for a single-tooth implant prosthesis.
      Both the rationale and the technique are presented. The successful use of an
      osseointegrated implant to support a fixed prosthesis is an accepted treatment
      modality in both the biologic and clinical dental communities. The clinical
      examination, the radiographic survey, and diagnostic casts all contribute to
      achieving an optimal esthetic result, but the final image may continue to be
      elusive until the healing of the second-stage surgery when the gingiva can be
      evaluated. The gold standard of success is providing an inconspicuous result.

PMID- 9161130
TI  - Interrelations of soft and hard tissues for osseointegrated implants.
AB  - Success in using osseointegrated dental implants-optimal function, esthetics, and
      phonetics-requires selection of the treatment modality that is optimal for the
      patient, protection of tissue blood supply, and adherence to a plan based on a
      thorough analysis of all deviations from the normal anatomy. The options for
      correction of hard-tissue deficiencies are mechanical modification of the
      implants and reconstructive surgery. Mechanical approaches reduce the time needed
      for reconstruction but direct the occlusal forces in unnatural directions.
      Surgical reconstruction is preferable. Any bone graft must be precisely fitted to
      the recipient site to facilitate revascularization. Restoration of hard-tissue
      dimensions usually requires soft-tissue coverage and augmentation. There are two
      basic options: (1) flaps with or without inlay or onlay grafts and (2) controlled
      tissue expansion. An onlay graft can help restore soft-tissue height and width.
      Inlay grafts have greater vascularity than onlay grafts, and the color matching
      is better. Controlled tissue expansion creates "like" tissue without a secondary
      defect, and fewer tissue transfers are needed. However, the technique is
      difficult, and the patient must make multiple visits to the office. For implant
      placement to be successful, the patient's expectations must be understood, and
      the benefit-to-risk ratio should be extremely high.

PMID- 9161132
TI  - Clinical use of an aerosol-reduction device with an ultrasonic scaler.
AB  - The traditional use of ultrasonic scalers has been to remove heavy deposits of
      calculus. Today, there is an increasing use of ultrasonic scalers in all areas of
      periodontal treatment, including periodontal maintenance and root planing.
      Coolant liquid must be used with an ultrasonic scaler because of heat buildup in
      the ultrasonic handpiece and scaler tip. The coolant liquid causes an infection
      control problem because of contaminated aerosols and a patient management problem
      because of water buildup in the patient's mouth. Data demonstrating the presence
      of blood in ultrasonic aerosols are presented. The clinical use of an aerosol
      reduction device that fits on an ultrasonic scaler is detailed. This device
      reduces the aerosol produced by more than 93%. Research that shows a reduction in
      water buildup in the patient's mouth of more than 76% (P < .01) is presented. The
      aerosol reduction device appears to greatly reduce many of the problems
      associated with the coolant liquid used during ultrasonic scaling.

PMID- 9161133
TI  - CEREC II: CAD-CIM for the twenty-first century.

PMID- 9161134
TI  - Total quality management: achieving service excellence.
AB  - Total Quality Management (TQM) provides a philosophy and a method for
      organizational renewal and redesign. It is based on the principle that productive
      work is accomplished through processes. Improving these processes requires the
      office team to objectively measure performance, discover root causes of problems,
      take corrective action, determine the effect of these actions, and secure
      achievements. TQM is a technique that provides a series of steps and set of
      tools. Through staff involvement and a desire for quality improvement,
      organizations involved in total quality note the accompanying satisfaction in
      taking constructive action, improving patient relations, and achieving service
      excellence. In today's competitive delivery environment, implementation of TQM
      can result in more satisfied patients, higher staff morale, and a more effective
      office team.

PMID- 9161135
TI  - Combined internal medicine and pharmaceutical electronic reference resources:
      Part 2.

PMID- 9161136
TI  - Customized emergence profile in the implant crown--a new technique.
AB  - As single-tooth replacement becomes an accepted part of daily practice, demands
      for optimum esthetics in implant-supported crowns increase. Most healing
      abutments and transfer copings are round and do not simulate the normal cross
      section of anterior teeth, resulting in unnatural sulcular form around implant
      abutments. This article presents a simple and economical method to develop and
      reproduce an optimum emergence profile in the implant crown using standard
      Nobelpharma components.

PMID- 9161137
TI  - Valuing dental practice.
AB  - Because new dentists are finding that initiating dental practices has become more
      problematic, the issues of practice purchase and valuation have become more
      salient. The purchase of a practice, although expensive, decreases the amount of
      time required before the dentist can experience a profit. This article discusses
      issues related to valuing, reviews some of the strategies related to the purchase
      of a practice, and recommends an objective approach to establishing fair market
      value.

PMID- 9161138
TI  - Passive motion therapy in temporomandibular joint disorders: the use of a new
      hydraulic device and case reports.
AB  - To understand the importance of motion on the structural and functional integrity
      of the temporomandibular joint (TMJ), the effects of immobilization and
      mobilization on synovial joints are reviewed. Impaired motion has profound
      deleterious effects on the synovial membrane, articular cartilage, muscles,
      ligaments, bone, and periarticular connective tissue. Conversely, motion has been
      shown to be essential to the maintenance of the structural and functional
      integrity of synovial joints. As in other synovial joints, the relative lack of
      the stimulus of mobility of the TMJ contributes to pathogenic mechanisms.
      Restoration of joint mobility is an important principle in the management of TMJ
      disorders. Illustrative cases are presented in which passive motion therapy,
      using a new device with a hydraulic mechanism, was successfully used for
      rehabilitation of TMJ function.

PMID- 9161139
TI  - A new pressed ceramic for esthetic rehabilitation.

PMID- 9161140
TI  - Controversies in clinical endodontics: Part 1. The significance and filling of
      lateral canals.
AB  - Controversies have been common in the clinical treatment of endodontically
      involved teeth for many years. This series of articles discusses the advantages
      and disadvantages of four of the major disagreements in the field at this time.
      They are: (1) What is the significance of lateral canals and how are they best
      filled? (2) Should treatment be completed in a single appointment or should
      multiple appointments be involved? (3) Can the canal(s) be filled after the tooth
      is left open or should such treatment be avoided? (4) What is the best way to
      calculate the working length? This article discusses the centerpiece controversy
      lateral canals. Subsequent articles will consider the other three subjects.

PMID- 9161141
TI  - Posterior crossbites in children.
AB  - Posterior crossbite, the most common malocclusion in young children, can be
      caused by a variety of skeletal, muscular, or dental factors. This condition
      produces insufficient maxillary arch width and is frequently associated with
      various oral sucking and postural habits. If left untreated, this problem can
      result in adverse skeletal growth changes. Various mechanical treatment
      modalities designed to expand the posterior maxillary arch width are available to
      correct this problem. The appropriate treatment method depends on the patient's
      age and level of cooperation as well as the determined etiology of the
      constriction.

PMID- 9161142
TI  - Wear rates of various artificial tooth materials: a literature review.
AB  - Current artificial tooth materials include acrylic resin, improved resin, filled
      polyurethane dimethacrylate, and porcelain. The improved materials have been
      popularized by their ability to resist abrasion. A wide variety of abrasives,
      measuring instruments, and methods of wear testing make it difficult to assess
      study results that compare these materials. Clinical trials are needed to help
      establish a standard laboratory test.

PMID- 9161144
TI  - Physiologic occlusion vs pathologic occlusion and rationale for treatment.
AB  - Treatment concepts in dentistry are generally based on a preconceived normal
      state derived from clinical observation and theories rather than scientific
      evidence. Before treatment is proposed, the clinician should observe physiologic
      signs and symptoms to determine the presence of a particular pathology. This
      article presents different theories of occlusion, diagnostic characteristics that
      can be used to distinguish between physiologic occlusion and pathologic occlusion
      requiring treatment, and guidelines for reconstructive occlusal therapy.

PMID- 9161143
TI  - The occlusal bite splint--a noninvasive therapy for occlusal habits and
      temporomandibular disorders.
AB  - Traumatic occlusion and occlusal habits, such as clenching and grinding, are the
      cause of many dental problems. These etiologic factors must be considered and
      evaluated when treating the dental patient. Early diagnosis and construction of a
      reversible occlusal appliance is often the most effective, quickest, and least
      invasive means of therapy. Temporomandibular joint surgery, occlusal
      equilibration, reconstructive dentistry, orthognathic surgery, orthodontics, and
      psychotherapy have all been used with success in some cases. Such invasive, and
      costly, procedures should be considered only after occlusal bite splint therapy
      has been proven unsuccessful. Occlusal bite splints can be constructed from heat
      cured acrylic or light-cured composite. The composite splint is a new material
      that has minimal distortion, is comfortably worn, and can be constructed in the
      dental office in less than 30 minutes.

PMID- 9161145
TI  - Management of the anticoagulated dental patient.
AB  - An understanding of the primary mechanisms of hemostasis, including the
      coagulation pathways and the intrinsic, extrinsic, and common systems, is the
      basis for treating the anticoagulated patient. Two major anticoagulants are used
      for treating those who may be at risk for thromboembolic crisis. These drugs
      include Coumadin, which is an oral anticoagulant, and heparin, a parenteral
      anticoagulant, which is often used for acute thromboembolic episodes or for
      hospitalization protocols that include significant surgical procedures. The
      practitioner should be familiar with common dental drugs that can interact with
      anticoagulants and should consult with the patient's physician before
      administering any such drugs. By placing the patient into one of three dental
      treatment categories, appropriate anticoagulation therapy can be rendered to each
      patient according to his or her needs. Low-risk procedures require no change in
      anticoagulation medication. For moderate-risk procedures, withdrawal of
      anticoagulation medication 2 days before the procedure and verified with the PT
      the day of the procedure is indicated. For high-risk dental procedures, using a
      heparin protocol should be strongly considered. In all instances of dental
      treatment, the oral tissues should be treated atraumatically using local
      hemostatic measures for control of hemorrhage. Treating medically compromised
      patients who are on a variety of medications is becoming more common in dentistry
      today. Understanding the underlying disease and the appropriate protocol for
      treatment of anticoagulated patients reduces the risk of thromboembolism and
      hemorrhagic complications.

PMID- 9161146
TI  - Managed care, capitation, and managed competition: a brief primer.

PMID- 9161147
TI  - Is dentistry destined to follow medicine in managed care?
AB  - Our professional calling is to assist our patients in reaching and maintaining a
      state of good oral health. If managed care assists in that effort, that's good.
      However, if we can identify and eliminate poor dental HMOs and identify the
      quality plans, dentistry will begin to realize that keeping people well can be as
      financially and professionally rewarding as treating disease. Is dentistry headed
      down the same path as medicine? Unfortunately, the answer is not clear. What is
      clear is that managed care is here and will impact significantly on dentistry,
      both positively and negatively. An opportunity exists to mold managed care into a
      form that is acceptable to dentists and improve the oral health of Americans on a
      cost-effective basis. However, we as dentists must act, and react, in a rational
      and logical manner if we are to have a voice in shaping the future of dental
      benefits and how they will be provided.

PMID- 9161148
TI  - Hershey Foods Corporation: a case study in managed dental care.
AB  - Throughout the development and implementation of Health Smile. Hershey Foods has
      been committed to quality-based health plan options for its employees that serve
      as the route to cost-effective care. It is known that the company will need to
      make a short-term investment, rather than have unrealistic expectations of
      immediate cost savings. However, much of the long-term potential for Hershey
      Foods rests on the primary dentist's ability to use resources conservatively for
      the most effective patient outcomes. Health Smile represents Hershey Foods' best
      effort at forming a partnership relationship between a purchaser, provider, and a
      patient.

PMID- 9161149
TI  - Managed dental care in the HMO setting.
AB  - DHMOs are gaining in popularity, and are the fastest-growing dental managed-care
      product, primarily because of their ability to reduce premium and patient costs.
      Dentistry, because of the strong correlation between prevention and disease
      control, is more suited to a managed-care system than medicine. However, there
      remains a wide gulf between theory and practice, as the DHMO industry continues
      to evolve. Poorly designed programs will save money but create problems with
      patient satisfaction and unmet treatment needs. Well-designed programs use the
      principles of population management to bring large numbers of patients to
      maintenance oral health levels. In any event, the continuing growth and
      development of DHMOs will benefit patients, group purchasers, and the dentists
      who can understand and embrace the concepts of dentistry in the HMO environment.

PMID- 9161150
TI  - From repairing the consequences of disease to managed wellness: lessons from 20
      years of managing dental care.
AB  - As the 21st century approaches, dentistry will be challenged by multiple
      pressures. The demographic trends of a growing population are outpacing the
      supply of dental manpower. Economic trends, including fewer family wage jobs,
      less full-time employment, and more single-parent families, create pressure on
      the ability to afford dental care. Competitive and reform pressures continue in
      the health-care field and are gaining momentum in dental care. Even without these
      pressures, traditional dental approaches have not been able to address the bulk
      of the needs of the population, as indicated by published assessments of the
      dental health of various segments or the overall use of dental services in the
      country. The challenge created by these demographic, economic, and competitive
      pressures on the KPDCP and the dental profession as a whole is to shift away from
      the individual patient, disease-model repair and improve management of dental
      wellness as the means of improving access to dental services for an even greater
      number of people. This challenge can be met by implementing the currently
      neglected clinical knowledge contained in our dental literature, taking action to
      find answers for the things we do not know, and by applying our knowledge to
      preventing the onset and/or progression of dental disease, decreasing unneeded
      and/or ineffective treatments, and avoiding premature entrance into the cycle of
      rerestoration.

PMID- 9161151
TI  - Considerations and preparations for making managed care part of your practice.
AB  - The decision to integrate managed care into the traditional FFS practice is one
      that requires careful consideration. Should you decide that it offers your
      practice an attractive opportunity to fill empty chairtime while positioning the
      practice for positive growth, now may be an opportune time for involvement.
      Furthermore, embracing a new mind-set could prove to be an invaluable business
      move-change is essential, no matter which path is taken. Most consultants believe
      that dentists who expand their horizons now will maintain a competitive edge over
      those who stick with more traditional methods of operation. As with any industry,
      it is important to aim for where things are going, not for where they have been;
      the positive focus should be on the dental practice of the future. According to
      Reengineering the Corporation (HarperBusiness, 1993) by Hammer and Champy,
      businesses today must not forget the three Cs: customers, competition, and
      change. The book points out that the customers are in charge, the competition has
      intensified, and change is a constant. The decisions made now regarding the
      direction of dental practices will determine how dentists deal with the forces in
      this uncharted future.

PMID- 9161152
TI  - Managed dental care and its effect on dental specialties.

PMID- 9161153
TI  - Dental care delivery in 2005.

PMID- 9161154
TI  - Face masks: effective personal protection.

PMID- 9161155
TI  - Combined internal medicine and pharmaceutical electronic reference resources:
      Part 1.

PMID- 9161156
TI  - Crown lengthening: a surgical flap approach.
AB  - In many instances it is not possible to place a restoration margin without
      encroaching on the periodontal attachment apparatus. A surgical crown-lengthening
      procedure can provide a good solution to this common clinical problem. This
      article discusses indication and contraindication for surgical crown-lengthening
      procedures and presents an appropriate surgical technique.

PMID- 9161158
TI  - An open letter to the dental class of 1996.

PMID- 9161157
TI  - Outcome failures of endosseous implants from a clinical training center.
AB  - In an effort to provide realistic clinical information from a "real-world"
      environment, the present retrospective study was undertaken to assess outcome
      failures after implant placement in a dental school clinical training center. A
      database was kept of the clinical information and was analyzed according to
      established parameters for implant outcomes. The demographics showed that over a
      period of 6 years, 80 different operators with a wide range of clinical
      experience had inserted 1,263 implants in a diverse patient pool of 380
      individuals. Analysis of the outcomes showed a cumulative survival rate of 91.3%.
      The time of explantation, the type, size, and location of implants lost, and
      failure rates in smoking patients were also analyzed. The results indicated that
      the use of implants by operators with different levels of experience did not
      affect favorable outcomes.

PMID- 9161159
TI  - Using pulsatile pressure saline/antibiotic irrigation before reduction and
      fixation of infected mandibular fractures: literature review and report of two
      cases.
AB  - The efficacy of pulsatile pressure saline irrigation has been demonstrated in the
      orthopedic, surgical, and dental literature. However, its use for treating
      infected mandibular fractures has not been documented. This article reviews the
      literature concerning pressure irrigation. The pulsatile pressure
      saline/antibiotic irrigation technique and indications for its use during the
      treatment of infected mandibular fractures are demonstrated with two case
      reports. The pulsatile pressure saline/antibiotic irrigation system is a useful
      adjunct to the standard therapeutic modalities of infection management. It is
      also useful for managing infected mandibular fractures, especially when open
      reduction and internal fixation with bone plates have been planned.

PMID- 9161160
TI  - Practice management tips. Hiring: prepare for the best.
AB  - A great deal of preparation, time, and expertise are needed to find a good staff
      member. Remember to be clear about your expectations and formalize your
      requirements with a written job description. If you plan to run a classified ad,
      be sure to write one that stands out from the rest. Conduct exceptional
      interviews that allow applicants to be themselves and demonstrate their
      abilities. Don't take any shortcuts. Check references, conduct working
      interviews, and provide training with positive feedback. Your investment of both
      finances and time will be rewarded when you choose and hire a highly qualified
      employee who will be able to contribute to the success of your practice.

PMID- 9161161
TI  - Calcium sulfate: a 4-year observation of its use as a resorbable barrier in
      guided tissue regeneration of periodontal defects.
AB  - The concept of guided tissue regeneration has been with us since the early 1980s.
      There are a number of techniques available today that each have certain
      advantages and disadvantages. This article describes one practitioner's
      experience with a new technique using calcium sulfate as a resorbable barrier as
      well as part of a composite graft using decalcified demineralized freeze-dried
      bone allograft. The technique is described, and some of the advantages to its use
      are listed.

PMID- 9161162
TI  - Rigid-fixation palatal appliances.
AB  - Palatal appliances can offer an alternative to the traditional treatment approach
      of cleft lip and palate. The goal of these appliances is to position the
      maxillary segments more ideally and then maintain their position while allowing
      growth to occur. Use of palatal appliances can minimize the iatrogenic growth
      restriction usually associated with cleft palate repair. This article presents
      the findings of clinical treatment at the Medical College of Georgia.

PMID- 9161163
TI  - Perceptibility of defects in an aluminum test object: a comparison of the RVG-S
      and first generation VIXA systems with and without added niobium filtration.
AB  - OBJECTIVE: To compare the first generation VIXA (Gendex, Milan, Italy) and the
      RVG-S (Trophy Radiologie, Vincennes, France) for detection of defects in an
      aluminium test object at various exposures both with and without added niobium
      filtration. METHODS: Images of a 7 mm aluminium test object with defects ranging
      from 0.1 to 1.5 mm with standardized projection geometry. Seven dentists acted as
      observers. Perceptibility curves were developed for both sensors under the
      various filtration conditions and exposures. RESULTS: At optimum exposures both
      the VIXA and the RVG-S permitted the same number of defects to be observed. The
      optimum exposures were similar for the two systems, but the dynamic range was
      greater for the RVG-S. Addition of niobium filtration did not appreciably alter
      the radiation dose required to perceive a given number of defects using either
      system. CONCLUSIONS: The two systems performed equally at optimum exposure when
      the dose is approximately the same irrespective of the presence or absence of
      niobium filtration. Beyond the optimal level, the RVG-S outperformed the VIXA
      system.

PMID- 9161164
TI  - Measurement accuracy: a comparison of two intra-oral digital radiographic
      systems, RadioVisiography-S and FlashDent, with analog film.
AB  - OBJECTIVES: To compare the accuracy of measurement algorithms incorporated into
      the software provided with two CCD-based digital radiographic systems and compare
      assessments using intra-oral film. METHODS: A test object with three radiopaque
      reference points was imaged using Ektaspeed intra-oral film, both with and
      without an overlaid 1 mm reference grid, the RVG-S, the measurement software of
      which overlays a 2 mm grid, and the FlashDent, which uses a mouse-driven cursor
      to estimate distances. Geometric factors, including source-to-object and receptor
      to-object distances, vertical and horizontal cone angulation, and vertical
      angulation of receptor, were successively altered. Six viewers estimated
      vertical, horizontal and diagonal distances for each image. RESULTS: Increased
      source-to-object distance resulted in a 5-10% reduction in image dimensions,
      whereas increased receptor-to-object distance produced a magnification of 15-20%
      with all techniques. Increased vertical and horizontal cone angulation resulted
      in slight increases in magnification (0-5%) whereas greater receptor angulation
      resulted in noticeable magnification under all test conditions (10-15%).
      Estimated values for vertical, horizontal and diagonal measurements were
      approximately 5-10% higher than the actual dimensions, irrespective of the
      technique used. The FlashDent mouse-driven cursor system and direct measurement
      of distances from conventional film were more accurate in horizontal and diagonal
      dimension estimates than using an overlaid grid. Intra-observer and inter
      observer differences were found for specific situations. CONCLUSION: The mouse
      driven computerized measurement cursor and intra-oral film assessment using a
      ruler provided the most accurate, reliable and consistent dimensional
      measurements.

PMID- 9161165
TI  - Intrafilm controls to standardize grey level variations in digitized radiographs.
AB  - OBJECTIVES: Radiometric analysis can be used to identify small changes in grey
      levels taken from investigator-defined regions of interest (ROIs). To do this,
      standardization of the radiographic optical densities and image grey scales is
      considered essential. Rigid standardization is one of the impediments to applying
      existing radiometric techniques to clinical practice. The purpose of this study
      was to evaluate the use of grey-level variations from a series of intrafilm
      control regions of interest (ROIs) to adjust radiometric grey-level data taken
      from test ROIs. METHODS: After digitization, ROIs were drawn on three locations:
      the background, anatomical crown, and tooth root. Mean grey levels, histograms
      and cumulative percent histograms (CPHs) were determined for each group. With the
      goal of decreasing the distribution of these curves from their unadjusted grey
      level positions to zero (superimposing all curves), shifts required to align the
      control CPHs were applied to test CPHs. Changes between the pre- and post
      adjusted CPH distributions were measured. RESULTS: Intrafilm controls provided a
      combined decrease of 45.3% in the grey-level distribution error. CONCLUSION:
      While CPHs can be adjusted using intrafilm controls, these adjustments may have
      limited benefit.

PMID- 9161166
TI  - Accuracy of dimensional and angular measurements from panoramic and lateral
      oblique radiographs.
AB  - OBJECTIVES: Dimensional and angular measurements from radiographs can be used in
      clinical dentistry to determine the inclination of impacted teeth, the relative
      position of roots and restorative abutments, and for implant site assessment.
      This study was carried out to assess the in-vitro accuracy of such measurements
      obtained from three rotational panoramic systems and two standardized lateral
      oblique projections (45 degrees and 60 degrees) using two cephalometric systems.
      METHODS: Acrylic test models with wires positioned to represent the position and
      angulations of the teeth were used. Ten images were taken with Oralix Pan DC/1,
      Panelipse and Orthophos panoramic machines. Fourteen lateral oblique radiographs
      were also taken using two cephalometric units: an Orthophos and a Quint
      Sectograph. The models were repositioned between each exposure. Horizontal,
      vertical and angular dimensions of every tooth position on each radiograph were
      measured by three evaluators and compared using ANOVA at an a priori significance
      level of alpha = 0.05. RESULTS: Assessment of vertical dimensions was
      consistently more accurate on lateral oblique projections than on the panoramic
      radiographs. In general, the most accurate horizontal measurements could also be
      made with the lateral oblique projections. No differences in angular measurement
      accuracy were found between any of the projections. The use of statistical means
      and standard deviations can be misleading in ranking accuracy where a consistent
      conversion factor can be applied. CONCLUSIONS: While panoramic radiography is
      convenient for dimensional and angular assessments, lateral oblique radiographs
      taken with a standard cephalometric apparatus are an alternative when greater
      clinical accuracy is needed.

PMID- 9161167
TI  - Accuracy in detecting bone lesions in vitro with conventional and subtracted
      direct digital imaging.
AB  - OBJECTIVE: To implement direct digital imaging (DDI) in subtraction radiography
      and compare the accuracy of conventional and subtracted DD images in detecting
      small bone lesions in vitro. METHODS: Alveolar bone defects were produced in a
      section of a pig mandible, with slow-speed burs 0.6, 0.7, 0.8, 0.9, 1.0, 1.2, 1.4
      mm in diameter. Standardized DD images were subtracted and displayed in black and
      white, contrast-enhanced and pseudo-colour transformed formats. 370 pairs of
      slides taken directly from the computer monitor were evaluated by eight
      observers. RESULTS: The area P(A) under the ROC curve with DDI was 0.67 +/- 0.1.
      This was significantly lower (p < 0.001) than any of the three modes of
      subtraction radiography (mean P(A) = 0.88 +/- 0.09). The detection of small
      lesions (bur diameter 0.6 mm) was significantly better (p < 0.001) with contrast
      enhancement. Observer agreement was smaller for DDI (chi = 0.22 +/- 0.09)
      compared with the subtraction images (mean chi 0.64 +/- 0.13) (p < 0.001).
      CONCLUSION: The diagnostic characteristics of the DDI system were significantly
      improved by digital subtraction with image processing.

PMID- 9161168
TI  - An approach to the development of decision support for diagnosing pathology from
      radiographs.
AB  - OBJECTIVES: Large inter-observer variation has been reported in oral radiology.
      Providing observers with a checklist prompting them to focus on specific
      radiographically visible features with known relevance to the diagnosis has been
      shown to improve diagnostic accuracy. We intended to investigate whether
      diagnostic accuracy for bony pathology could be improved by a computerized
      decision aid. The decision support provided the user with radiographic reference
      images for the degree of presence of a radiographic feature (such as radiopacity)
      and structured the use of diagnostic knowledge. METHODS: Twenty-seven general
      dental practitioners participated in the study. They diagnosed seven radiographic
      cases of bony pathology using a prototype decision aid and seven other cases
      unaided. For each radiograph the dentists assessed the degree of presence of five
      radiographically visible features which had been selected from the literature
      oral radiology because of their use in describing, radiographically visible bony
      pathology. The dentists' assessments of degree of feature presence, and their
      diagnoses, were recorded. Histopathology was used as a diagnostic 'gold
      standard'. The degree of presence of the features in the radiographic images was
      also assessed by an independently selected panel of expert oral radiologists in a
      Delphi consensus procedure. RESULTS: Determination of the degree of presence of
      three radiographically visible features assessed by the dentists using the
      prototype decision aid was significantly improved (by up to 12%) compared to the
      results of their unaided assessments. The diagnostic accuracy of one-third of the
      dentists was also improved. CONCLUSION: The use of reference images can improve
      dentists' assessments of the degree of feature presence.

PMID- 9161169
TI  - Temporomandibular joint disc position in arthrography. A descriptive analysis of
      the observer performance.
AB  - OBJECTIVES: To explore the relationship between the use of diagnostic cues and
      observer performance in the diagnosis of the temporomandibular joint (TMJ) disc
      position. METHODS: Thirty arthrographic examinations using fluoroscopy alone and
      combined with either transcranial radiography or tomography were selected. Seven
      observers assessed the examinations with the aid of reference images and written
      diagnostic cues for three disc diagnoses. After one month three of the observers
      repeated the assessments and noted how they applied the diagnostic cues. Later,
      they made a consensus report on how the cues were applied to each joint. RESULTS:
      The seven observers agreed unanimously with the reference diagnosis by
      fluoroscopy alone in 11 joints and in 14 when supplemented with transcranial
      radiography or tomography. Seven joints were given three different diagnoses by
      the seven observers when fluoroscopy was used alone and five when supplemented
      with transcranial radiography or tomography. The cues were applied with
      confidence in those joints where the observers were unanimous but in those with
      three different diagnoses, the anatomical features described in the cues were
      difficult to identify or the findings were ambiguous as they did not match the
      cues. CONCLUSIONS: It appears difficult to define radiographic cues applicable to
      all TMJ disc positions.

PMID- 9161170
TI  - Accuracy of caries diagnosis in digital images from charge-coupled device and
      storage phosphor systems: an in vitro study.
AB  - OBJECTIVES: To evaluate the diagnostic accuracy of carries detection with four
      intra-oral digital radiographic systems in vitro and to investigate the impact of
      image compression. METHODS: 116 extracted human premolars and molars mounted
      three in a line with approximal contacts were radiographed with four digital
      systems (Digora, RVG, Sens-A-Ray, and Visualix) and imported into a Windows-based
      program. Sixteen images from each system were compressed (JPEG, irreversible
      compression). The total of 528 images was assessed by six radiologists using a 5
      point confidence scale for the detection of approximal and occlusal caries.
      Caries was validated histologically. The disease threshold was caries in enamel
      for approximal surfaces and in dentine for occlusal surfaces. RESULTS: Mean ROC
      curve areas for approximal surfaces were 0.611 (DIG), 0.572 (RVG), 0.594 (SAR),
      and 0.596 (VIX), and for occlusal surfaces 0.794 (DIG), 0.819 (RVG), 0.751 (SAR),
      and 0.761 (VIX). There were no significant differences between the areas under
      the ROC curves (p > 0.05); nor were there any significant differences between the
      compressed and uncompressed images (p > 0.05). CONCLUSIONS: The four digital
      systems performed almost equally well for detection of caries in vitro, and
      compressed images were as accurate as uncompressed.

PMID- 9161172
TI  - Three-dimensional imaging of craniomaxillofacial structures with a standard
      personal computer.
AB  - OBJECTIVE: To implement 3D-reconstruction of CT and MR data by a standard MS-DOS
      personal computer. METHODS: User-specific software has been developed for the 3D
      reconstruction and quantitative evaluation of hard and soft tissues of the skull.
      RESULTS: The software displays a 3D-reconstruction and secondary reformatted
      vertical sections within 4-30 s on the monitor. The 3D-structures can be
      evaluated quantitatively with a freely-superimposable grid. Distances or angles
      between two landmarks can be measured directly. Various tools for the simulation
      of surgical treatment are available. CONCLUSIONS: Gross skeletal and soft-tissue
      malformations, topographical relations and the degree of asymmetry of severe
      maxillofacial deformities can be evaluated in more detail. Access to a readily
      available low-cost computer system for 3D-evaluation of the head will enable a
      larger number of clinicians to use 3D-methods in diagnosis and treatment
      planning. The off-line computing system permits a higher of flexibility
      independent of any computing centre.

PMID- 9161171
TI  - Effect of image magnification of digitized bitewing radiographs on approximal
      caries detection: an in vitro study.
AB  - OBJECTIVE: To evaluate whether or not image magnification of digitized bitewing
      radiographs had an effect on approximal caries detection. METHODS: Twenty general
      dental practitioners (GDPs) rated a total of 140 digital images (28 approximal
      surfaces at five different magnifications, x3, x6, x12, x18 and x30) for caries
      on a 5-point confidence scale. The observations were compared with the state of
      the approximal surfaces on visual inspection. For each GDP the average response
      rate was calculated. Paired t-tests were used to compare the diagnostic response
      at the five different image magnifications. RESULTS: The mean response rates
      obtained at x18 and x30 magnifications were significantly inferior to those at
      the three smaller magnifications (p < 0.007). CONCLUSION: Digital image
      magnification has a significant influence on observer performance in the
      detection of approximal caries, with an upper limit beyond which diagnostic
      accuracy may be reduced. Further research is needed to determine limits for
      various different diagnostic tasks so as to give GDPs guidelines on the
      appropriate magnifications to use.

PMID- 9161173
TI  - Dental implant treatment planning with reformatted computed tomography.
AB  - By using specific software programmes, it is now possible to obtain reformatted
      CT images of the mandible and maxilla. This facility has proved to be valuable in
      the planning of fixed and removable suprastructures in implantology. We describe
      the use of a radiopaque prosthetic template to enable the optimal position and
      axial inclination of the fixtures in edentulous patients to be established.

PMID- 9161174
TI  - Concavity of the posterior surface of the temporomandibular condyle: clinical
      cases and autopsy correlation.
AB  - OBJECTIVES: To elucidate the significance of the radiographic finding of a
      concavity of the posterior surface of the temporomandibular condyle. METHODS:
      Three clinical cases with a concavity were followed up clinically and
      radiographically. A total of 39 temporomandibular joint (TMJ) autopsy specimens
      were examined by corrected sagittal tomography and seven condyles with a
      concavity of the posterior surface found. They were analysed microscopically
      together with three joints with a normal, rounded condyle. RESULTS: At follow-up
      tomography, two of the clinical cases revealed no change while the third patient
      had erosive changes after 7 months. The microscopic findings of the autopsy
      specimens varied. The articular cartilage in three of the seven joints with a
      concavity was similar to that in the normal condyles. The outer surface of the
      articular cartilage was sometimes uneven and the cartilage thickened, with an
      irregular junction between the articular cartilage and subchondral bone. In three
      joints the cartilage in the concavity had been replaced by granulation tissue.
      All seven joints had increased cellular activity in the concavity. CONCLUSIONS:
      The radiographic finding of a concavity in the posterior surface of the condyle
      is not specific. When small and well-defined it is indicative of remodelling and
      of osteoarthrosis when larger and with a diffuse outline.

PMID- 9161175
TI  - The role of caries recognition: treatment decisions from bitewing radiographs.
AB  - OBJECTIVE: To describe the effect of the ability to estimate caries depth from
      bitewing radiographs on restorative treatment decisions. METHODS: A 10% random
      sample of Dutch dental practitioners (n = 444) was sent a two-part questionnaire
      based on an analytic approach to radiographic caries diagnosis and restorative
      treatment decision making. In the second part the dentists were asked to diagnose
      radiographs of 105 tooth surfaces with and without dentine caries and then to
      make a treatment decision for each surface. A regression analysis was carried out
      using the negative predictive value (TN/[TN + FN]) of the restorative treatment
      decision for dentine caries as the dependent variable. RESULTS: The mean negative
      predictive value for the dentists' proposals from radiographs to leave surfaces
      untreated was 0.77 (SD 0.05; min. 0.60, max 0.87). Nine significant (P < 0.05)
      variables explained 65% (R2 = 0.65) of the variation in decision making. One
      diagnostic ability variable explained 48% of the variation found. CONCLUSIONS:
      Dentists appear to take the seriousness of errors in restorative decisions into
      account when deciding on treatment. The ability of dental practitioners to
      identify and discriminate between lesions in the inner half of the enamel and the
      outer half of the dentine, however, plays a dominant role in their treatment
      decision making.

PMID- 9161176
TI  - Evidence-based evaluation of three imaging methods for the temporomandibular
      disc.
AB  - OBJECTIVES: To review the literature and evaluate the evidence for the diagnostic
      outcome of arthrography, computed tomography (CT) and magnetic resonance imaging
      (MRI) in the assessment of temporomandibular joint (TMJ) disc position. METHODS:
      A literature search from 1978 to 1994 was conducted. Data on sensitivity,
      specificity, predictive values and likelihood ratios were collected and, if not
      available, calculated for each imaging method. Measures of observer performance
      were also recorded. RESULTS: In total, more than 400 publications were retrieved
      on imaging of TMJ disc position, 219 on arthrography, 99 on CT and 147 on MRI,
      with a marked decrease in recent years. The majority of the publications (54%)
      presented series of patients. The diagnostic outcome cold be obtained from only
      7% of the studies and the observer performance from only two of these.
      Arthrography had the highest diagnostic outcome for the diagnosis of anterior
      disc position; sensitivity 0.90, specificity 0.80, positive predictive value 0.88
      and negative predictive value 0.82. Corresponding figures for CT were 0.66, 0.68,
      0.66 and 0.74 and for MRI 0.86, 0.63, 0.67 and 0.83. The diagnostic outcomes
      expressed as the likelihood ratios for positive test outcome were 4.5 for
      arthrography, 2.3 for MRI and 2.1 for CT. The outcomes in diagnosing sideways and
      rotational displacements were higher for MRI (sensitivity 0.81, specificity 0.87,
      positive predictive value 0.82, negative predictive value 0.88) than for
      arthrography (0.64, 0.83, 0.70, 0.79). The likelihood ratios were 6.2 for MRI and
      3.8 for arthrography. The interobserver performance ranged between moderate to
      substantial for arthrography and was almost perfect for MRI. CONCLUSIONS: Based
      on current evidence on the diagnostic outcome, MRI seems to be the method of
      choice for diagnosing TMJ disc position. Arthrography has a higher diagnostic
      outcome for anterior disc position but the disadvantage of being an invasive
      method. We suggest that the quality of the evidence should be improved and that
      an analysis of the impact of the imaging methods on patient treatment should be
      performed.

PMID- 9161177
TI  - Interventional radiology for the non-surgical removal of sialoliths.
AB  - OBJECTIVES: To clarify the usefulness and limitations of interventional radiology
      for sialolithiasis. METHODS: Sixteen patients (5 with parotid and 11 with
      submandibular sialolithiasis) were treated with a stone retrieval catheter
      (Dormia basket) under fluoroscopy. Digital subtraction sialography (DSS) and
      direct digital dental imaging (RVG) were performed in addition for 11 of the
      cases (DSS for 7 and RVG for 4 cases). RESULTS: The sialolith was successfully
      removed in 10 cases. DSS and RVG were useful. Four cases failed because the stone
      was adherent to the ductal wall and two because the catheter could not reach the
      stone because of the ductal anatomy. CONCLUSION: Interventional radiology is less
      invasive than surgical treatment and is the recommended first choice for
      treatment in the majority of cases of sialolithiasis.

PMID- 9161178
TI  - A 6-year clinical assessment of electronic facial thermography.
AB  - OBJECTIVE: To report the findings a 6-year clinical application of ET on patients
      with orofacial pain. METHODS: ET was conducted (in a blinded manner) using an
      Agema 870 unit at 0.1 degree C thermal accuracy. A newly devised thermal
      classification system was applied: 'normal' when zone delta T was from 0.0 to +/
      0.25 degree C, "hot' when zone delta T was > +0.35 degree C, 'cold' when zone
      delta T was < -0.35 degree C, and 'equivocal' when zone delta T was +/-(0.26
      0.35) degree C. Study populations consisted of 164 dental patients mainly with
      diagnostic problems and 164 matched (control) subjects. RESULTS: Our prospective,
      matched study determined that subjects with 'hot' thermograms had the clinical
      diagnoses of sympathetically maintained pain, peripheral nerve mediated pain, TMJ
      arthropathy, and maxillary sinusitis. Subjects with 'cold' thermograms were found
      to have the clinical diagnoses of peripheral nerve-mediated pain and
      sympathetically independent pain. Subjects with 'normal' thermograms were found
      to have the clinical diagnosis of cracked tooth syndrome, trigeminal neuralgia,
      pretrigeminal neuralgia, or psychogenic facial pain. The new system of thermal
      classification resulted in 92% (301 of 328) agreement in classification of pain
      patients and matched controls. CONCLUSION: These studies suggest that ET has
      promise in aiding the formation of a differential diagnosis of orofacial pain and
      may help in understanding mechanisms of pain as well as directing therapies.

PMID- 9161179
TI  - Correction of background noise in direct digital dental radiography.
AB  - OBJECTIVES: To clarify the source of noise in direct digital intra-oral
      radiography with RVG-S (Trophy Radiologie, Vincennes, France) and to use these to
      develop a method for correction of background noise. METHODS: Sensor temperature,
      image acquisition time and X-ray dose were independently analysed with the IPLab
      Spectrum (Signal Analytics, Vienna, VA) software. RESULTS: The decrease in pixel
      value due to the dark current was linearly related to the image acquisition time.
      Although a variation in sensitivity was observed when the sensor was exposed to X
      rays, the mean pixel value of the entire image was linearly related to the
      exposure time. The image showing only the signal due to X-ray dose was derived
      from the original RVG-S image by correcting for the dark current and the pixel-by
      pixel sensitivity variation of the CCD sensor. CONCLUSION: The image formed only
      by X-ray dose distribution can be derived by correcting for the background noise.

PMID- 9161180
TI  - Usefulness of panoramic radiography in the diagnosis of postmenopausal
      osteoporosis in women. Width and morphology of inferior cortex of the mandible.
AB  - OBJECTIVES: To evaluate the usefulness of width and morphology of the inferior
      cortex of the mandible on panoramic radiographs in the diagnosis of
      postmenopausal osteoporosis. METHODS: The width and morphology of the mandibular
      inferior cortex on panoramic radiographs were compared with trabecular bone
      mineral density (TBMD) of the 3rd lumbar vertebrae (L3) measured by dual energy
      quantitative computed tomography in 29 premenopausal and 95 postmenopausal women.
      RESULTS: There was a significant negative correlation between the width
      (Kendall's tau = -0.36, p < 0.001) and morphology (Kendall's tau = -0.49, p <
      0.001) of the mandibular inferior cortex and the L3 TBMD. Regression analysis
      showed that significant linear relationships were observed between the L3 TBMD
      and age (p < 0.001), cortical width (p < 0.05), morphology (p < 0.05),
      controlling body mass index, number of teeth present and menopausal status (R2 =
      0.42). CONCLUSION: Our results suggest that panoramic radiography could be
      reliable in screening for osteoporosis.

PMID- 9161181
TI  - Comparison of linear measurements made from storage phosphor and dental
      radiographs.
AB  - OBJECTIVES: To compare linear measurements made from storage phosphor and dental
      radiographs. METHODS: Five dry hemimandibles were imaged with an 8 x 10-inch
      (20.3/25.4 cm) high-resolution storage phosphor plate and Ektaspeed Plus occlusal
      size dental film. Optimal exposure was empirically determined for the dental
      films. Reductions in exposure of 50 and 75% were used for the storage phosphor.
      Three observers made linear measurements between end-points of lines and center
      points of fiducials on clinical specimens, dental radiographs, digitized dental
      radiographs and storage phosphor images. Data were analysed with repeated
      measures and nested analysis of variance. RESULTS: Measurements obtained from
      optimally exposed dental films and reduced-exposure storage phosphor images were
      equivalent to clinical measurements recorded from dry hemimandibles. Less than 2%
      of variation among measurements was attributable to the five modalities.
      CONCLUSION: No substantive difference was detected between linear measurements
      obtained from the storage phosphor or dental radiographis. Because storage
      phosphor images require no chemical processing, can be used at reduced exposure
      and are inherently digital, they are a viable alternative to dental film for
      making linear measurements.

PMID- 9161182
TI  - Identification of the temporomandibular joint and adjacent cephalometric
      landmarks using a dual sensitivity screen-cassette system.
AB  - OBJECTIVES: Clinical evaluation of a cassette with dual speed screens for
      cephalometric radiography. METHODS: Two lateral cephalometric radiographs were
      taken on 20 consenting subjects using the TMJ Orthoceph Slimline Cassette System
      (TOSCS), incorporating circular Trimax 12 screens in the area adjacent to the
      temporomandibular joint, and a control cassette (Trimax 8 screens). Ten pairs of
      radiographs with optimal image quality were randomly presented to 10 observers
      trained in cephalometric interpretation. Observers rated the overall diagnostic
      quality of each radiograph and of the TMJ region on an ordinal scale. They then
      located specific landmarks and traced the TMJ anatomy using acetate overlays.
      Overlays were digitized by a single operator who repeated tracing placements and
      digitizations to determine the error of recording method. Landmark variability
      was compared in the x- and y-axis by the Wilcoxon matched-pairs signed ranks test
      (p < 0.05). Six repeat tracings were performed and assessed by percentage of
      repeated observations above the maximum affordable error. Fossa space values were
      analyzed by the coefficient of variation (CV). The variability of the angular and
      linear values was also compared. RESULTS: TOSCS image quality was perceived as
      significantly better than the control. Method error was 0.34 mm in the x-axis and
      0.4 mm in the y-axis. Interobserver variability was 2 to 3 times greater than
      intraobserver. There was less variability with TOSCS for identification of basion
      (x-axis), center-of-rotation (x-axis) and condyle (posterior) (x-axis). However,
      this was clinically insignificant. Accurate determination of the fossa space was
      not possible as CV varied from 23 to 84%. No differences in the variability of
      angular or linear values variability were found. CONCLUSIONS: While observers
      preferred TOSCS, no significant clinical differences could be demonstrated
      between the two systems.

PMID- 9161183
TI  - Case report. Two contrasting radiological presentations of prostatic
      adenocarcinoma in the jaws.
AB  - The contrasting radiological appearances of metastatic deposits in the mandible
      of prostatic adenocarcinoma in two patients are described. The clinical
      presentation was similar in that both presented with altered sensation of the
      lower lip. Radiologically, they differed in that one patient suffered from a
      large predominantly osteoblastic mass, while the other, who gave a history of
      previously treated prostatic adenocarcinoma, presented with a rather small
      osteolytic deposit. Investigations for bony metastatic disease usually include a
      bone scan which is a highly sensitive technique although non-specific. A skeletal
      survey can be useful although less sensitive than a bone scan. Blood
      investigations such as acid phosphatase and prostate specific antigen levels are
      also indicated in male patients where prostatic disease is suspected. Reasonable
      long term survival using relatively simple drug therapy without significant local
      surgery, highlights the need for accurate recognition and tissue diagnosis to
      differentiate this condition from osseous malignancy of the jaws, other
      metastatic disease or osteomyelitis.

PMID- 9161184
TI  - Case report. synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO)
      syndrome.
AB  - A case of the SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis)
      syndrome in a 35-year-old woman is presented. Ignorance of this entity on the
      part of the physicians treating the patient may have contributed to her having
      repeated diagnostic procedures and treatment, some of which may have been
      unnecessary. Dentists are encouraged to suspect the SAPHO syndrome when they
      encounter a patient with mandibular osteomyelitis together with symptoms
      involving other bones and skin lesions such as pustulosis or psoriasis.

PMID- 9161185
TI  - Case report. Magnetic resonance features of metastatic melanoma of the
      temporomandibular joint and mandible.
AB  - We report a case of histologically verified melanoma of the nose which presented
      2 years after initial radiotherapy with left temporomandibular pain, dysfunction
      and dental sepsis. Conventional radiography revealed a partially dentate mandible
      with a destructive lesion involving the left condyle, an ill-defined lesion in
      the right retromolar region and chronic inflammatory apical root lesions. Since
      MRI of the nose was done at the initial presentation, it was postulated that MRI
      could be used to characterize the destructive jaw lesions. The MR features were
      similar to the original nasal lesion and accepted as proof of diagnosis of
      metastatic melanoma. A literature review reveals only 37 previous cases of
      metastasis to the temporomandibular joint with none of involvement by melanoma.
      The role of MRI in the diagnosis of this lesion is also described for the first
      time.

PMID- 9161186
TI  - Technical note. Sagittal tomography as an adjunct to cross-sectional evaluation
      of select implant sites.
AB  - OBJECTIVE: To supplement conventional cross-sectional tomography with a sagittal
      projection in order to verify the location of vital anatomical structures prior
      to dental implant surgery. METHODS: A method is described that illustrates the
      theory, technique and benefits of incorporating sagittal tomography into the
      radiographic examination of a dental implant patient. RESULTS: Local variations
      in the inferior-superior position of the mandibular canal or encroachment of the
      sinus on areas immediately adjacent to the proposed maxillary implant site can be
      demonstrated. CONCLUSIONS: The additional information gained from sagittal
      tomography aids the clinician in appreciating the orientation and morphology of
      the anatomical area under examination.

PMID- 9161187
TI  - Technical note. Modulation transfer function analysis of a newly revised
      rotational panoramic machine.
AB  - OBJECTIVES: To determine the modulation transfer function (MTF) and noise
      equivalent passband (NE) values for a newly revised rotational panoramic X-ray
      machine, the PC-1000 (Panoramic Corp., Fort Wayne, Indiana, USA). METHODS: Images
      of a 10 microns test slit were taken at various locations along the X-ray beam
      projection path using a Lanex Regular/T-Mat G image receptor. Line spread
      functions were obtained at specific beam paths by scanning slit images with a
      microdensitometer. RESULTS: MTF values were highest around the central plane of
      the image layer, with a maximum near the centre of 0.25 at 4 cycles/mm. The NE
      values near the central plane of image layer were 1.4 cycles/mm. MTF and NE
      values in the anterior region were low, 0.2 and 1.2, respectively. The width of
      the image layer was narrower in the anterior and wider in the posterior segments.
      Rapid decreases in MTF and NE values were found on the X-ray tube side compared
      with the receptor side of the central plane. Using a spatial frequency of 0.25
      MTF the shape of the image layer was coincident with that determined visually.
      CONCLUSION: On the basis of the MTF and NE values the image resolution produced
      by this machine is considered acceptable for panoramic dental radiography.

PMID- 9161188
TI  - Trends in caries experience of 12-year-old children in east European countries.
AB  - This paper reviews published data on the caries experience of 12-year-old
      children in east European countries, including the 14 states of the former Soviet
      Union. With the exception of the Czech Republic (2.7) all DMFT indices in the
      east European countries were within the range of 3.1 (Bulgaria) to 5.1 (Poland).
      For the states of the former Soviet Union the DMFT indices were higher in the
      northern regions (range 3.3 in Belorussia to 7.7 in Latvia) than in the southern
      regions (1.2 in Tadzikistan to 3.1 in Kirgizia). Other than in southern states of
      the former Soviet Union, 'low' or 'moderate' caries experience (by WHO criteria)
      were found only in countries with developed oral health care systems. In most of
      the other countries implementation of oral health promotion and prevention at the
      community level is needed.

PMID- 9161189
TI  - The dental management of children with sickle cell disease and beta-thalassaemia:
      a review.
AB  - This paper reviews two groups of haemoglobinopathies: sickle cell disorders and
      beta-thalassaemias. The medical aspects and dental management of children with
      these conditions are discussed. These conditions are rare in the white indigenous
      population of the UK but affect a sizeable proportion of the minority ethnic
      community. Dentists need to be aware of the medical implications for patients who
      have these disorders and should co-ordinate their dental care accordingly.

PMID- 9161190
TI  - Fissure sealing with a light-cured resin-reinforced glass-ionomer cement
      (Vitrebond) compared with a resin sealant.
AB  - The aims of the present study were to evaluate the retention and caries
      preventive effect of a single application of a light-cured resin-reinforced glass
      ionomer cement (Vitrebond) in pits and fissures of newly erupted permanent first
      and second molars, when compared with a single application of a resin-based
      sealant (Concise White Sealant) during a 3-year period. The study group comprised
      73 pairs of contralateral newly erupted permanent first and second molars (136
      fissure sites) in 53 children (29 girls, 24 boys). A split-mouth experimental
      design was used in which the two sealants were randomly allocated to one of the
      teeth within each pair. Acid etching was not used before application of the glass
      ionomer cement. The sealed teeth were checked for retention and caries after 1,
      6, 12, 24 and 36 months. The resin-based sealant was almost totally retained
      after 3 years (97%) and there was no caries in these teeth. The glass-ionomer
      cement was increasingly lost and could be observed in only 9% of the sealed sites
      after 3 years. Carious lesions developed in 10 (7.4%) sites (nine teeth, seven
      children). It was concluded that the resin-based sealant is superior to the glass
      ionomer cement in preventing caries, and that the superior retention of the resin
      probably is an important factor for this.

PMID- 9161191
TI  - Questionnaire evaluation of feeding methods for cleft lip and palate neonates.
AB  - A questionnaire evaluation was undertaken of feeding methods used by the mothers
      of 25 neonates with cleft lip and/or palate. Most parents had problems feeding
      their babies, both with the quantity of food taken and especially with the time
      taken to feed; even after a period of 2 months over a quarter were still having
      problems with the quantity of feed and a third had not established a regular
      feeding pattern. Just over a half needed to change the feeding method from the
      one with which they started. Twelve of the 25 mothers tried to breast-feed but
      none of them was successful. The Haberman feeder was the most popular, being used
      by 18 mothers. An acrylic feeding plate was considered to be helpful by 6 of 11
      mothers of babies with complete clefts but by only 1 of 9 mothers of babies with
      secondary palate clefts. Almost all the mothers were dissatisfied with the
      information they had received while in hospital and with the back-up when they
      went home.

PMID- 9161192
TI  - A partial double-blind, placebo-controlled study of electronic dental anaesthesia
      in children.
AB  - This study was carried out to determine the effectiveness of electronic dental
      anaesthesia (EDA) in restorative dental treatment for children. Thirty children
      were allocated at random to three groups to receive either EDA, a placebo-EDA or
      anaesthesia by oral injection. One dentist, having introduced and administered
      these procedures, completed an occlusal restoration in a maxillary permanent
      first molar in each child. The results showed that the children changed the EDA
      controls in accordance with pain assessed by their reports and by their facial
      signs counted in video records by an observer. Both the children and the observer
      were 'blind' to the difference between EDA and placebo-EDA. There were no
      statistical differences in: (1) the number of additional oral injections required
      in all groups to complete treatment, (2) the depth of cavity prepared, (3) the
      frequency of disruptive activities, (4) the dentist's management behaviour, (5)
      the dentist's rating of the children's disruptiveness, (6) pain estimated by the
      children's reports and by facial signs. Treatment time was shortest in the oral
      injection group, but had no significant correlation with any measure of pain,
      disruptive behaviour or depth of cavity. It was concluded that EDA was no less
      effective than anaesthesia administered by injection but, being no more effective
      than a placebo-EDA, probably worked by distracting the patients.

PMID- 9161193
TI  - Characteristics of primary dentition occlusion in a group of Saudi children.
AB  - Occlusal characteristics of the primary dentition vary among populations and
      ethnic groups. This cross-sectional study aimed to record various primary
      dentition parameters in 520 3-5-year-old randomly selected Saudi children and to
      observe the differences between the age groups. 80% of the children had a 'flush
      terminal plane' molar relationship. The proportion of the children with 'distal
      step' molar relationship was significantly lower at age 5 (7%) than at age 3
      (16%). 86% of the children had Class I canine relationship, with no significant
      differences between the age groups. The degree of overbite was significantly less
      in the 5-year-olds than in the 3-year-olds. The majority of the children (76%)
      had an overjet of 0-2 mm, but the prevalence of 0-1 mm overjet was significantly
      higher, and that of 2-3 mm significantly lower, in the elder age group. The
      prevalence of anterior crossbite was 2% and of posterior crossbite 4%. The
      prevalence of malocclusion was lower in these subjects than in some Caucasian
      populations.

PMID- 9161194
TI  - A survey of factors influencing the prescribing of sugar-free medicines for
      children by a group of general medical practitioners in Northern Ireland.
AB  - Factors which influence the prescribing of sugar-free medicines by 47 general
      medical practitioners were examined by means of questionnaire. The doctors all
      practise in the Newry and Mourne district of the Southern Health and Social
      Services Board, Northern Ireland. Twenty-six (55%) of the doctors stated that
      they support the principle of prescribing sugar-free medicines for children; the
      same number stated that they oblige parental requests and 14 (30%) stated that
      they frequently prescribe a common group of sugar-free medicines. However, only
      14 (30%) of the doctors considered that their knowledge of sugar-free medicines
      was up-to-date. The main sources of information about sugar-free preparations
      were drug company travelling representatives and professional journals, but a few
      doctors learned of this issue from other professionals, including dental
      practitioners. The majority of doctors (especially those with a practice policy
      of prescribing sugar-free medicines) felt it was important to prescribe sugar
      free preparations for all children, not only for those requiring long-term
      medication. The results show that there is a reasonable level of interest in this
      issue among the doctors in the area, but that there is an on-going need for
      further encouragement and provision of information for them, in order to increase
      as far as possible the use of sugar-free preparations for children.

PMID- 9161195
TI  - Acquired toxoplasmosis of a submandibular lymph node in a 9-year-old boy
      diagnosed by fine-needle aspiration cytology.
AB  - Toxoplasmosis is a parasitic infection which may be asymptomatic or produce
      lymphadenopathy, fever and malaise. In children the cervical lymph nodes are most
      commonly affected. This report describes a case of a 9-year-old boy who presented
      with submandibular lymphadenopathy associated with a non-vital primary tooth,
      which persisted following extraction of the tooth. A diagnosis of acquired
      toxoplasmosis was made on the findings of fine-needle aspiration cytology and
      subsequently confirmed by serological investigations, thus sparing the patient
      unnecessary hospitalization and surgery. The patient required amitryptyline as a
      nocturnal sedative and made a complete recovery within a few months without the
      need for further intervention.

PMID- 9161196
TI  - Congenital mucoceles: report of two cases.
AB  - Congenital mucoceles are very rare. Only two previous cases presenting in the
      neonatal period have been reported. Two cases are presented here, one arising
      within the tongue and the other in the floor of the mouth. In both cases the
      mucoceles became apparent soon after birth because they interfered with mouth
      closure and normal feeding. The cysts were surgically excised and
      histopathological examination showed that they were retention cysts. The infants
      quickly resumed normal oral function and swallowing after surgical removal.

PMID- 9161197
TI  - The use of a special mouthguard in the management of oral injury self-inflicted
      by a 4-year-old child.
AB  - This paper describes the management of self-inflicted trauma by a 4-year-old boy
      who was mentally retarded as a result of encephalitis in infancy. There was
      severe damage to his lower lip, as well as a moderate degree of injury to the
      skin and nail of his right thumb. Preliminary intervention was made with a
      mouthguard using silicone elastomeric positioner material, which soon proved
      ineffective because of poor retention. The problem was overcome successfully
      through use of a special appliance in which a heat-cured acrylic base was
      combined with a superstructure made of silicone positioner material retained
      mechanically with retention loops of 0.7 mm orthodontic wire.

PMID- 9161198
TI  - Insights into maxillary and mandibular growth for a better practice.
AB  - By understanding the growth mechanisms of the maxilla and mandible and using four
      key concepts of Neuro-Occlusal Rehabilitation, better treatment can be rendered
      to the patients with malocclusions and chewing disturbances. This paper relates
      these concepts with experimental data.

PMID- 9161199
TI  - A sub-occlusal oblique transverse ridge: identification of a previously
      unreported tooth structure: the Rainey Ridge.
AB  - This article identifies a previously unreported structure of mandibular molars,
      which can best be described as a sub-occlusal oblique transverse ridge. A
      predominant feature of this ridge as it underlies the anatomical landmark
      commonly referred to as the central "fossae," is its interconnection of the disto
      lingual cusp and the mesio-buccal cusp. This ridge and other web structures found
      in enamel are important considerations when preparing teeth using ultra
      conservative dentistry.

PMID- 9161201
TI  - Posterior bite raising effect on the length of the ramus of the mandible in
      primary anterior crossbite: case report.
AB  - Posterior occlusal acrylic resin blocks were bonded to the mandibular primary
      molars. This removes incisal interferences while correcting the anterior
      crossbite with Utility Archwire Appliance. Since the first permanent molars were
      not included in the occlusal coverage, the permanent molars were free to erupt to
      a new plane of occlusion. This resulted in an increased length of the ramus by 11
      mm and counterclockwise rotation of the mandible is reported.

PMID- 9161200
TI  - Dental anomalies in the primary dentition: distribution and correlation with the
      permanent dentition.
AB  - The study consisted of analysis of all cases of anomalies in the primary
      dentition that were seen or treated by the authors in the Department of
      Children's Dentistry and Orthodontics. A total of 79 occurrences of anomalies was
      seen in 65 children. The anomalies detected were double teeth, hypodontia and
      supernumerary teeth. Radiographic examinations of the affected children showed
      that over 60% of the cases with anomalies in the primary dentition are associated
      with anomalies of the succadeneous permanent dentition. All subjects with
      hypodontia of the primary dentition presented with hypodontia of the permanent
      dentition. However, anomalies of the permanent dentition were seen in 59% of
      subjects with primary double tooth and 50% of subjects with primary supernumerary
      tooth.

PMID- 9161202
TI  - Confusion as a technique to induce hypnosis in a severely anxious pediatric
      dental patient.
AB  - Hypnosis may be the tool of choice in patients who reject or otherwise cannot
      receive pharmacological modalities, or behavioral interventions. It is a state of
      mind in which suggestions are not only more readily accepted than in the waking
      state, but also acted upon much more powerfully than would be possible under
      normal conditions. Confusion is one of many techniques, which may aid the
      practitioner in inducing hypnosis. A case of using confusion to induce hypnosis
      in an extremely anxious 13-year-old girl in the dental office is presented.

PMID- 9161203
TI  - Ectopically erupting mandibular first permanent molar: treatment of a case.
AB  - This case report presented a rare case of irreversible ectopic eruption of right
      mandibular first permanent molar in a 6-year-old boy. Distal root resorption of
      primary second molar was found during routine radiographic examination. Early
      treatment of ectopically erupting permanent first molar was considered in favor
      of preventing space loss. Using a modified Humphrey appliance as the correcting
      appliance, the ectopic eruption of permanent first molar had been successfully
      uprighted and retained.

PMID- 9161205
TI  - Regional odontodysplasia: a case report.
AB  - This patient presents with a regional odontodysplasia in the mixed dentition with
      the upper right quadrant being affected from the anomaly. The upper right first
      primary molar was extracted because of a periapical abscess and examined scanning
      electron microscopically. The aim of this article is to discuss the clinical and
      ultrastructural features of the anomaly and revise the other odontodysplasia
      cases reported in the literature.

PMID- 9161204
TI  - Regional odontodysplasia: review of the literature and report of a case.
AB  - Regional odontodysplasia is a rare and unique dental developmental anomaly that
      affects tooth morphogenesis. This case is unusual in that it involved the
      mandibular dentition. However, in this case the mandible was unilaterally
      involved. The presence of an abscess in relation to the lower right first
      permanent molar, in the absence of deep caries or periodontal pathology was an
      interesting finding. The radiographic appearance of bizarre pulpal morphology
      with high pulp horns extending to the occlusal surface would provide an open
      communication between the pulpal tissue and oral cavity. The importance of the
      first permanent molar as a strategic tooth was recognized and an apexification
      procedure was performed. The care and treatment of a child with odontodysplasia
      requires a multidisciplinary approach. In this case the right lower primary
      cuspid and first primary molar had been extracted previously. The early
      extraction of these teeth and the subsequent delay in hard tissue formation and
      eruption of the permanent successors could have resulted in altered growth of the
      alveolus in this region.

PMID- 9161206
TI  - Space maintainer effects on intercanine arch width and length.
AB  - In order to investigate the effects of space maintainers in intercanine arch
      width and length, twenty cases, characterized with the early loss of mandibular
      primary molars were selected and divided into two groups. The treatment group
      used removable space maintainers, while the other ten cases served as the control
      group. The first dental casts of the treatment and control groups were obtained
      when the primary canines were in the mouth. After the eruption of permanent
      canines second dental casts were obtained in both groups. Six measurements were
      made on the dental casts of each patient. No parameter was found to be
      statistically significant in the treatment group. In the control group the
      increase in intercanine arch width and perimeter were found to be statistically
      significant. Also the increase at the buccal and lingual bone measurements were
      found to be statistically significant. These results showed that space
      maintainers might cease the increase in intercanine arch width and length during
      the transition period between the primary and permanent canines.

PMID- 9161207
TI  - Alveolar bone loss and restorative dentistry in the primary molars.
AB  - This study examined the relationship between the status of the interproximal
      alveolar bone and the nature of the adjacent proximal surfaces in the primary
      molar area. In bite wing radiographs of 354 children, aged 6 to 9 years, 5091
      sites were examined; 72.7% of the sites were adjacent to intact proximal
      surfaces, 14.2% to untreated proximal carious surfaces, and 13.0% to restored
      proximal surfaces. Marginal alveolar bone loss (ABL) was evident in 26.8% of the
      children, at 4.0% of the sites. Two thirds of the children with ABL had bone
      defects in more than 1 site. Males had a significantly higher mean number of
      sites affected with marginal ABL, per child, than females (mean = 2.4, SE = 0.2
      and mean = 1.8, SE = 0.2 respectively). ABL was found adjacent to: 0.8% of the
      intact surfaces; 16.9% of the carious surfaces; 7.8% of the restored surfaces;
      1.8% and 53.8% of the sites without or with proximal contact loss respectively;
      3.8% and 30.8% of the sites with or without an adequate amalgam restoration
      respectively; 4.9% and 25.8% of the sites with an adequate or inadequate crown
      restoration respectively. The differences in distribution of marginal alveolar
      bone loss were highly significant (Chi square analysis, p = < 0.0001) for sites
      with intact, carious or restored sites, and for the presence or absence of
      contact loss, adequate amalgam or adequate crown.

PMID- 9161208
TI  - Surface morphology of sound enamel after argon laser irradiation: an in vitro
      scanning electron microscopic study.
AB  - Argon laser irradiation (ALI) at relatively low fluences (energy densities)
      enhances the caries resistance of sound enamel. The purpose of this SEM study was
      to compare the effects of argon laser irradiation at relatively low fluences
      (11.5 Joules/cm2 and 100 Joules/cm2) on enamel surface morphology. Following a
      fluoride-free prophylaxis, 12 extracted caries-free human molars were sectioned
      into tooth quarters. Tooth quarters were treated as follows: 1) Mesiobuccal-ALI
      at 11.5 J/J/cm2 for 10; 2) Distobuccal-Control; 3) Mesiolingual-ALI at 100
      J/J/cm2 for 10; and 4) Distolingual-Control. Enamel surface morphology was
      compared among the two argon laser irradiation groups and matched non-treated
      control enamel surfaces by SEM. Argon laser treatment resulted in considerable
      alterations in the surface morphology compared with matched controls. Control
      enamel surfaces showed relatively smooth contours with occasional termination of
      enamel prisms at the surface. Both argon laser treatment groups had intact enamel
      surfaces lacking prism end markings and cratering of the enamel surface. A
      discontinuous granular surface permeated by numerous microporosities of < 1.0
      micron in diameter was created with both argon laser treatment groups. Globular
      deposits of approximately 0.5 to 2 microns in maximum dimension composed the
      surface coatings. These deposits were admixed with areas of fine microporosities.
      Argon laser irradiation at relatively low fluences produces surface coatings
      which may act as reservoirs for mineral phases during an acidogenic attach of the
      enamel and may provide a certain degree of protection against a cariogenic
      challenge.

PMID- 9161209
TI  - Kinetic cavity preparation: protection of the cavo-surface enamel.
AB  - A significant defect of kinetic cavity preparation systems is damage to cavo
      surface sound tooth enamel. The purpose of this study is to establish a
      protective method for cavo-surface sound tooth enamel during air-powder abrasive
      system cavity preparation, using protective varnish. A total of 39 extracted
      human primary teeth were used for this experiment. Protective varnish was applied
      to the tooth surface in single, double and triple coats. The kinetic instrument
      was used for cavity preparation. Class V cavities were prepared on the border
      area of varnish coated and intact tooth surface. After removal of varnish with a
      supersonic washer, specimens were dried and gold plated with ion-spatter,
      following which cavity margin enamel was observed through a SEM. Tooth surface
      enamel where coated with varnish appeared intact and the cavo-surface margin
      remained at a right angle form. However, tooth surface enamel without varnish
      coating appeared rough, and the cavo-surface margin exhibited a round shape. It
      seems likely that kinetic energy was absorbed by the soft varnish coating,
      thereby protecting the enamel. Protective varnish was found to provide a
      protective effect for cavo-surface sound enamel, and was also found to promote a
      sharp edge at the cavo-surface margin, during kinetic cavity preparation.

PMID- 9161210
TI  - Class II composite resin restorations using glass-ionomer liners: microleakage
      studies.
AB  - Microleakage studies were undertaken for Class II composite resin restorations
      that had been lined with glass-ionomer cement using the 'sandwich' technique.
      Thirty freshly extracted permanent molars and premolars were mounted in
      polymethylmethacrylate blocks. Class II cavities were prepared using carbide burs
      No. 245 in a water cooled dental handpiece, (cavity box 5 x 3 x 2 mm). Specimens
      were divided into three groups of 10 each. Group A was restored with hybrid
      composite resin only, Group B with hybrid composite using a light-cured glass
      ionomer liner applied to dentin only, and Group C with hybrid composite using
      light-cured glass-ionomer liner carried out to the cavosurface margin, (beyond
      the DEJ). All the specimens were thermocycled between 5 degrees C and 55 degrees
      C for 250 cycles for 3 hours, followed by placement in 0.5% aqueous basic fuchsin
      dye for 24 hours at 37 degrees C. Specimens were sectioned mesio-distally through
      the restorations using an Isomet apparatus. The extent of dye penetration was
      scored under a stereomicroscope with reference to the DEJ, (0 = no penetration, 1
      = penetration to the enamel, 2 = penetration beyond the DEJ). Statistical
      analysis of the data showed significant differences among the means of the groups
      at p < 0.001. The results of this study indicate that the application of a light
      cured glass-ionomer up to the cavosurface margin inhibits the microleakage of
      Class II restorations in vitro.

PMID- 9161212
TI  - Tunnel restorations using glass ionomer or glass cermet: in vitro marginal ridge
      fracture and microleakage.
AB  - The purpose of this in vitro study was to compare the marginal ridge fracture
      resistance and microleakage following restorations of partial tunnel preparations
      using glass ionomer and glass cermet cements. Sixty eight sound premolars were
      selected for this study and were divided randomly into six groups. A standardized
      partial tunnel preparation was done on all the teeth except specimens belonging
      to Group I. The partial tunnel preparations of Groups III & V were restored with
      glass ionomer and that of Groups IV & VI were restored with glass cermet. The
      teeth belonging to Groups I, II, III & IV were subjected to marginal ridge
      fracture resistance testing. The teeth of Groups V & VI were tested for
      microleakage after immersing them in 5% methylene blue solution for 4 hours. The
      results indicated that the teeth restored with glass cermet were marginally
      better than that with glass ionomer in terms of marginal ridge fracture
      resistance. Both the materials failed to reinforce the marginal ridge to the
      level of an intact tooth. The microleakage which occurred around both the
      materials were statistically insignificant, but on comparison glass ionomer
      showed better results. Hence, glass ionomer is preferred as a restorative
      material for partial tunnel preparations because of additional inherent
      advantages like superior esthetics and fluoride leachability.

PMID- 9161211
TI  - Resin-modified glass ionomer restorations in primary molars: a comparison of
      three in vitro procedures.
AB  - In recent years, interest in the use of glass ionomer cements as a restorative
      material has been increased. The aim of this in vitro study was to evaluate the
      microleakage of a glass ionomer restorative material (Vitremer TM) in Class V
      cavities of primary molars using three different application procedures. The
      experimental material consisted of 24 freshly extracted human primary molars in
      which a standardized class V cavities were prepared and restored with Vitremer
      utilizing three different application procedures (Vitremer with conditioner, with
      conditioner and primer or with primer). Teeth were covered with green stick
      compound and nail polish except approximately 1 mm from the class V cavities
      margins. Later, teeth were immersed in 5% methylene blue for 4 hours, rinsed with
      water and embedded in acrylic resin. The marginal microleakage was assessed
      according to the degree of dye penetration of the occlusal and cervical margins.
      The results showed no significant difference between the three different
      application procedures. However, the occlusal margin microleakage was
      significantly higher than the cervical margin (P = 0.0079). It was concluded that
      using different application procedures of Vitremer, including the recommendations
      of the manufacturer does not affect microleakage of class V cavities in primary
      molars.

PMID- 9161213
TI  - Multiple supernumerary teeth in association with cleidocranial dysplasia.

PMID- 9161215
TI  - A second look at expanded functions research: unintended outcomes for the
      public's safety.

PMID- 9161214
TI  - Infection control knowledge, practice, and attitudes of Mississippi dental
      hygienists.
AB  - PURPOSE: The purpose of this study was to assess Mississippi dental hygienists'
      knowledge and use of infection control techniques, attitudes pertaining to
      universal precautions and the risk of clinician/patient cross-infection, and
      attitudes toward treatment of patients with infectious diseases. METHODS: A 41
      item questionnaire was mailed to all 508 licensed dental hygienists in
      Mississippi. Inactive, retired, and out-of-state hygienists (n = 59) were deleted
      from this study. The data were tested for significant associations using Chi
      square. RESULTS: After adjusting for the 59 unusable returns, the response rate
      for analysis was 58% (n = 297). Dental hygienists reported using infection
      control techniques including sterilization or disposal of common items such as
      prophylaxis angles, suction tips, and air/water syringe tips. Although 98% of the
      respondents believed that barrier techniques were effective, some believed
      patients infected with HIV/AIDS (43%), hepatitis B (31%), or tuberculosis (40%)
      are best treated in public clinics rather than in private settings and that these
      clients pose a threat to dental hygiene practitioners. Further, a majority of the
      respondents believed that all oral healthcare workers and patients should be
      tested for HIV/AIDS. CONCLUSIONS: The incongruity between perceived knowledge,
      reported practice, and attitudes suggests the need for continuing education
      courses designed to allow dental hygienists to explore the affective domain
      regarding the care of patients with infectious diseases. In addition, courses on
      working with patients with HIV/AIDS should be offered in smaller cities for
      greater accessibility.

PMID- 9161216
TI  - Dental hygienists in Hong Kong: present and future status.
AB  - PURPOSE: This study assessed the current employment status of dental hygienists
      practicing in Hong Kong, investigated factors affecting their employment,
      evaluated the satisfaction of local dental hygienists and their employers, and
      explored the career prospects of dental hygienists in Hong Kong. METHODS: All
      registered dental hygienists (n = 64), all dentists who employed dental
      hygienists (n = 25), and a systematic sample of dentists who did not employ
      dental hygienists (n = 278) were surveyed in June 1994 concerning employment
      situation, salaries, job satisfaction, and opinions on future prospects for
      dental hygienists. RESULTS: Response rates were 86% for dental hygienists (n =
      55), 88% for employers (n = 22), and 63% for dentists at large (n = 175). Among
      the dental hygienists, 87% still were employed as dental hygienists, and both the
      dental hygienists and their employers agreed that the employment situation was
      satisfactory; however, several dental hygienists were considered to be working
      below their level of qualification. Major reasons for dentists not to employ a
      dental hygienist were having only one operatory and having an inadequate number
      of patients. In general, employers expressed satisfaction with the performance of
      the dental hygienists. Major reasons for employing a dental hygienist were that a
      dental hygienist would add professional and economical benefit to their clinic.
      Few dentists would support expanded duties for dental hygienists. CONCLUSIONS: In
      Hong Kong, dental hygienists and their employers comprise a small group with
      limited impact on oral healthcare services. Dental hygienists' perceptions of
      their future roles and ambitions are higher than those of their employers. To
      further the development of dental services in Hong Kong and meet documented oral
      healthcare needs in the population, greater utilization of dental hygienists
      should be promoted.

PMID- 9161218
TI  - Tobacco education and cessation interventions.

PMID- 9161217
TI  - Domestic violence identification and referral.
AB  - This report reviews the dental, medical, nursing, and public health literature
      concerning domestic violence prevalence, morbidity, mortality, education, and
      legislation. The primary goal of this report is to increase awareness of the
      signs of suspected domestic violence and the importance of being involved in
      prevention and early intervention. A second goal of this report is to increase
      awareness of domestic violence and to encourage the dental hygiene community to
      investigate methods to intervene and prevent this increasing problem. For dental
      hygienists, the commitment to learn and to help others should drive the
      initiative to address this concern for the well being of society. Due to the
      nature of domestic violence and our tendency to avoid involvement in the personal
      lives of others, this issue may be difficult for some people to encounter. It is
      through professional and continuing education that we strive to be better
      informed and equipped to venture effectively into this arena. Lastly, we are
      obligated to adhere to the commitment of the Dental Hygiene Code of Ethics by
      promoting public public health and safety for all in the community, the nation,
      and the world.

PMID- 9161219
TI  - An investigation of dental hygiene treatment fear.
AB  - PURPOSE: The purpose of this study was to develop and test the psychometric
      properties of a dental hygiene fear survey in a convenience sample population
      from a Midwestern metropolitan area. METHODS: A convenience sample of 300
      subjects from two sites, a suburban general dental practice and a dental school
      intramural faculty practice located in a metropolitan area, was utilized. A 16
      item instrument was developed that incorporated the University of Washington
      Fears Clinic four subtypes of dental fear: fear of specific stimuli, generalized
      anxiety, distrust, and catastrophe. The survey was administered prior to dental
      hygiene treatment. Scores were summed and patients were classified as
      experiencing dental hygiene fear if their scores were greater than one standard
      deviation above the mean. Reliability was estimated by Cronbach's alpha. Validity
      was examined by correlating the revised instrument with measures of conceptually
      related variables. RESULTS: Cronbach's alpha coefficient was .85 for specific
      dental hygiene stimuli, .79 for generalized anxiety, .75 for distrust, and .68
      for fear of catastrophe while receiving dental hygiene treatment. Overall
      reliability of all 16 items was estimated at .92. A significantly positive
      correlation (.58) was found between dental hygiene patients who reported high
      fear and avoidance (> 2 years) of dental hygiene treatment (p < .05). Dental
      hygiene fear correlated negatively (-.12) with age (p < .05). Females reported
      dental hygiene fear more frequently than males. CONCLUSIONS: Further revisions of
      the Dental Hygiene Fear Survey are needed; however, this survey shows promise in
      evaluating dental hygiene fear.

PMID- 9161220
TI  - Infection control protocols for exposing and processing radiographs.

PMID- 9161221
TI  - Oral cancer screening--are we doing our part?

PMID- 9161222
TI  - Adult clients' recall of oral health education services received in private
      practice.
AB  - PURPOSE: The purpose of this study was to determine adult clients' recall of oral
      health education services they received in private practice settings. METHODS: A
      written questionnaire was completed by a convenience sample of 199 adult clients
      who each had an appointment at a university dental hygiene clinic. Responses were
      statistically analyzed to generate frequency distributions of recall of oral
      health education services received in private practice and to determine if
      statistical differences existed in the number of services recalled according to
      selected client characteristics. RESULTS: The results indicated that 14 of the 22
      oral health education services included on the questionnaire were reported to
      have been provided to fewer than half of the study participants when they were
      treated in their private dental care setting. The subjects were most likely to
      recall they were given a toothbrush. Chi-square analysis of selected client
      characteristic variables indicated that only four of the services were
      statistically significant between the reported frequencies and client age and
      periodontal health status. The differences between the reported frequency of
      services for females and males were not statistically significant. Subjects
      recalled that more oral health education services had been provided in
      conjunction with a prophylaxis by a dental hygienist; the differences in the
      reported frequencies for 16 of the 22 services were statistically significant. (p
      < or = .05) CONCLUSIONS: The convenience sample and data constraints, which
      depended on the clients' recall of services received in a private practice
      setting, must be considered in interpreting the results. Even though dental
      hygienists provide more oral health education services than other oral healthcare
      practitioners, the generally low frequencies of adult client recall of oral
      health education services received in private practice settings indicate that
      oral healthcare providers may not incorporate effective learning strategies into
      their health education programs.

PMID- 9161223
TI  - Infection control practices of Rhode Island dental hygienists and certified
      dental assistants.
AB  - PURPOSE: Limited studies document the infection control practices of dental
      hygienists and dental assistants even though both groups play a vital role in the
      prevention of disease transmission in the dental office. The purpose of this
      study was to survey Rhode Island registered dental hygienists and certified
      dental assistants to (1) determine their current infection control practices; (2)
      to document attendance at an infection control course; and (3) to identify the
      need for additional infection control education. METHODS: In October of 1993 a
      fixed-response survey was mailed to a random sample of 267 registered dental
      hygienists (RDHs) and 260 certified dental assistants (CDAs) in Rhode Island.
      Data were analyzed using descriptive statistics, cross-tabulations, and the chi
      square statistic. RESULTS: Responses were received from 171 RDHs and 153 CDAs for
      adjusted response rates of 64% and 59%, respectively. Most responding RDHs and
      CDAs were wearing gloves but substantially fewer were utilizing one of the two
      acceptable combinations of personal protective barriers. Other procedures that
      were not always practiced by a substantial number of respondents included the use
      of disposable barriers, following recommended handwashing protocol, utilizing
      appropriate procedures for disinfection and sterilization of dental instruments
      and handpieces, updating medical histories, and biological monitoring of
      sterilization equipment. Although the majority of both groups reported having
      attended an infection control course within the past year, having written
      infection control protocols in place, and being satisfied or very satisfied with
      the level of infection control, many recommended procedures were not practiced
      routinely. CONCLUSIONS: These findings indicate that lack of compliance with
      infection control guidelines is multifactorial. Even though there is a need for
      continuing infection control education for dental hygienists and certified dental
      assistants, education alone is not the answer.

PMID- 9161225
TI  - Vive la difference.

PMID- 9161224
TI  - Work load, fatigue, and pause patterns in clinical dental hygiene.
AB  - PURPOSE: Previous studies have suggested that high frequencies of shoulder and
      neck complaints in dental hygienists mainly were due to longstanding, low-level
      static load of the neck and shoulder muscles. The purpose of the present study
      was to make continuous recordings of myoelectric signals from the shoulder
      muscles of dental hygienists in order to assess static load. METHODS: Myoelectric
      signals were recorded from the right trapezius muscle of 10 Swedish dental
      hygienists during half of a normal working day. A portable system for collection
      and on-line processing of myoelectric signals was used. Signal parameters were
      obtained, indicating muscular load, fatigue, pause frequency, and pause duration,
      respectively. All measurements were referred to a resting value and a reference
      contraction value established with the hand loaded with a 0.5 kg weight at the
      beginning of the recording session. RESULTS: A static load of 50 to 100% of the
      reference contraction (0.5 kg hand load with raised arm) was found in the
      trapezius muscle. The median load for the whole group was 57% of the reference
      level. Group data analyses of frequency EMG seldom showed significant fatigue. At
      individual levels, however, it was possible to identify localized muscle fatigue
      and relate it to a specific work task. There were many short pauses with a
      duration of 1 to 2 seconds, but an almost total lack of pauses of a duration
      longer than five seconds. CONCLUSIONS: Individual dental hygienists exhibited
      significant muscle fatigue that might be related to development of work related
      myalgias of the shoulder muscles. Future study of muscle patterns and dental
      hygiene tasks may lead to improved work designs and patterns for dental
      hygienists.

PMID- 9161226
TI  - Correlations between anatomic and MRI sections of human cadaver temporomandibular
      joints in the coronal and sagittal planes.
AB  - Cadaver material was used in this study to correlate sequential sagittal and
      coronal T1-weighted magnetic resonance images against anatomic detail. Magnetic
      resonance imaging (MRI) was found to accurately represent soft tissues in normal
      and deranged joints. In contrast to previous reports, MRI was found to accurately
      represent the discal-retrodiscal junction and did not appear to give false
      positive findings for disc displacement. Magnetic resonance imaging provided good
      images of bony outline, particularly in coronal views. Difficulties in
      interpretation arose when different adjoining tissues produced the same MR image;
      the central tendon of the lateral pterygoid muscle can appear as an extension of
      the disc, imaging as a distorted and displaced disc. In anatomic sections, a
      medial hernia sac in the lower joint space was seen as a constant indicator of
      the medial component of disc displacement; however, this was not evident in
      sagittal and coronal T1-weighted images. Fibrocartilaginous remodeling of the
      articular surface projecting into a discal perforation presented the same image
      as normal discal tissue. Because discs are often thinned over the lateral pole,
      it is difficult to determine whether discal tissue is present between the
      articular surfaces when MRI is at its present resolution. Subcortical bone spaces
      may be misinterpreted as areas of avascular necrosis and osteochondritis
      dissecans. It is recommended that an imaging sequence of the TMJ include a
      midcondyle image and lateral, central, and medial sagittal images; however, the
      lateral sagittal image is the most difficult to interpret.

PMID- 9161227
TI  - Neural structures within the sheep temporomandibular joint.
AB  - To better understand pathologic processes associated with arthritis of the
      temporomandibular joint (TMJ), detailed information on the innervation of TMJ
      tissues in normal as well as arthritic joints is needed. The aim of this study
      was to describe the normal innervation of the sheep TMJ in preparation for using
      this animal as a model for the study of the effects of arthritis on joint
      innervation. The macroscopic and microscopic appearance plus the distribution of
      neural structures within the TMJ were examined using fluorescence histochemistry
      (glyoxylic acid), immunohistochemistry (calcitonin gene-related peptide), silver,
      and gold chloride techniques. Joints from 10 mature merino sheep were studied.
      Calcitonin gene-related peptide-immunoreactive nerve fibers were found in the
      capsule and the synovial membrane, but not in the disc. Nerve bundles and single
      nerve fibers in the capsule, synovial membrane, and the peripheral 2 to 3 mm of
      the disc were stained by glyoxylic acid. Ruffini, paciniform-type, and Golgi
      organ nerve endings plus free nerve endings were located in the capsule, with the
      highest density of nerve endings occurring at the site of attachment of the disc
      to the capsule. The highest density of neural structures (using gold chloride)
      was in the posterior part of the joint. The highest density of autonomic fibers
      (using glyoxylic acid) was in the anterior capsule. The highest density of
      sensory fibers (using calcitonin gene-related peptide) was in the synovial and
      subsynovial tissues of the anterior capsule. These results confirm the existence
      of autonomic and sensory nerves in the capsule, synovial membrane, and peripheral
      disc in healthy adult sheep.

PMID- 9161228
TI  - The influence of deep (odontogenic) pain intensity, quality, and duration on the
      incidence and characteristics of referred orofacial pain.
AB  - This study examined the effects of the intensity, quality, and duration of
      odotogenic pain on the incidence, pattern, and clinical characteristics of pain
      referral in the orofacial region. Four hundred consecutive patients reporting
      with posterior toothache to the dental emergency clinic were included. Patients
      completed a standardized clinical questionnaire consisting of a numerical rating
      scale for pain intensity and chose verbal descriptors from a list of adjectives
      describing the quality of their pain. In addition, patients indicated sites to
      which pain referred by drawing on a mannequin* of the head and neck. Pain
      intensity was found to significantly affect the presence of referred pain (P <
      .005). However, neither duration nor quality of pain influenced the incidence of
      referred pain. Finally, pain referral occurred in vertical laminations as
      indicated on mannequin drawings, but these were not found to be diagnostic
      because of extensive horizontal overlap. The association of intensity and
      referral is attributed to central nervous system hyperexitability causing
      expansion of receptive fields and spread and referral of pain.

PMID- 9161229
TI  - Comparing TMD diagnoses and clinical findings at Swedish and US TMD centers using
      research diagnostic criteria for temporomandibular disorders.
AB  - The Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD)
      guidelines, originally developed in the United States, were translated and used
      to classify TMD patients on physical diagnosis (Axis I) and pain-related
      disability and psychologic status (Axis II) in a TMD specialty clinic in Sweden.
      The objectives of the study were to determine if such a translation process
      resulted in a clinically useful diagnostic research measure and to report initial
      findings when the RDC/TMD was used in cross-cultural comparisons. Findings
      gathered using the Swedish version of the RDC/TMD were compared with findings
      from a major US TMD specialty clinic that provided much of the clinical data used
      to formulate the original RDC/TMD. One hundred consecutive patients were enrolled
      in the study. Five patients with rheumatoid arthritis and 13 children or
      adolescents were excluded. The remaining 82 patients participating in the study
      comprised 64 women and 18 men. Group I (muscle) disorder was found in 76% of the
      patients; Group II (disc displacement) disorder was found in 32% and 39% of the
      patients in the right and left joints, respectively; Group III (arthralgia,
      arthritis, arthrosis) disorder was found in 25% and 32% of the patients in the
      right and left joints, respectively. Axis II assessment of psychologic status
      showed that 18% of patients yielded severe depression scores and 28% yielded high
      nonspecific physical symptom scores. Psychosocial dysfunction was observed in 13%
      of patients based on graded chronic pain scores. These initial results suggest
      that the RDC guidelines are valuable in helping to classify TMD patients and
      allowing multicenter and cross-cultural comparison of clinical findings.

PMID- 9161230
TI  - A cross-sectional study of prevalence and etiology of signs and symptoms of
      temporomandibular disorders in high school and university students.
AB  - The aim of this study was to evaluate the prevalence and need for treatment of
      temporomandibular disorders (TMD) in students living in Bauru, Brazil. The role
      of occlusal and emotional factors was also addressed. The presence and severity
      of TMD was determined by using a self-reported anamnestic questionnaire composed
      of 10 questions regarding common TMD symptoms. The symptoms were transposed into
      a severity classification according to the number and frequency of positive
      responses. Occlusal evaluation included an analysis of retruded contact position,
      intercuspal position, anterolateral guidance, and nonworking side contacts during
      mandibular movements. Palpation of the muscles and temporomandibular joints were
      performed to detect clinical signs of TMD. A chi square test was used to compare
      clinical and occlusal data with the presence and severity of TMD. A total of
      0.65% of the subjects had severe TMD symptoms, 5.81% had moderate symptoms, and
      34.84% had mild symptoms. Those with severe and moderate symptom levels were
      interpreted to be in need of treatment. Symptoms were found significantly more
      frequently in females than in males (P < .01). Self-reported emotional tension
      and parafunctional habits demonstrated strong associations with TMD (P < .01).
      Occlusion did not seem to influence the presence or severity of TMD. Based on
      these results, the efficacy of some traditional TMD treatments should be
      reconsidered, and reversible and conservative procedures should be the first
      choice for managing TMD patients.

PMID- 9161231
TI  - The reporting of pain, somatic complaints, and anxiety in a group of patients
      with TMD before and 2 years after treatment: sex differences.
AB  - The aim of this study was to assess possible gender differences regarding the
      reporting of pain, somatic complaints, and anxiety in a group of patients
      suffering from temporomandibular disorders (TMD). The group consisted of 40
      females and 13 males who received conservative TMD treatment comprising
      counseling, muscle exercises, and a stabilization splint. Before and 2 years
      after treatment, the patients answered three questionnaires (McGill Pain
      Questionnaire [Norwegian version] including a six-point scale, the Present Pain
      Intensity; a Somatic Complaints Questionnaire; and the trait part of
      Spielberger's State-Trait Anxiety Inventory. Before treatment, females reported
      greater present pain intensity than did males. Two years after treatment, females
      reported less sensory and emotional pain than at the initial stage; males
      presented no reduction in these pain scores. There were no gender differences at
      either stage regarding somatic complaints or anxiety level scores.

PMID- 9161232
TI  - Criteria for the detection of sleep-associated bruxism in humans.
AB  - Surface electromyography of the masseter and electrocardiogram recordings of
      heart activity during sleep were performed on nine subjects who suffer from an
      oral motor dysfunction (bruxism during sleep. Signals were monitored in the
      subject's home sleeping environment over 4 consecutive nights. A total of 36
      nights of data were analyzed to perform the following: (1) describe the nature
      and magnitude of total masseter muscle electromyographic activity above a minimum
      threshold of 3% of each subject's individually established maximum voluntary
      contraction level; and (2) describe electrocardiograph rate changes (using the R
      R interval) that occurred in relation to these electromyographic elevations. From
      these data, criteria for detection of bruxism events were established and
      combined into a fully automated event detection algorithm. The mean number and
      duration of the detected bruxism events are reported. The underlying logic for
      the criteria selected, and what effect other possible criteria would have on the
      separation of abnormal from normal motor events, is also presented and discussed.

PMID- 9161233
TI  - Paradigm shift.

PMID- 9161234
TI  - The role of sympathetic activity in neuropathic orofacial pain.
AB  - Seventeen patients with neuropathic orofacial pain are presented with reference
      to precipitating events, pain descriptions, response to treatment, and other
      aspects of their histories and clinical presentation. Stellate ganglion blocks
      were done on 14 patients. Ten of 14 patients reported temporary relief of pain
      with stellate ganglion blocks. Five of these patients noted more prolonged
      improvement in pain, two reported no change, and two experienced a temporary
      increase in pain. It is argued that sympathetically maintained pain involving
      orofacial locations does occur and that stellate ganglion blocks may benefit a
      subgroup of these patients. It is noted that current diagnostic categories are
      inadequate to describe a subgroup of these patients. New categories are
      suggested, and further study is recommended.

PMID- 9161235
TI  - Effects of salmon calcitonin on patients with atypical (idiopathic) facial pain:
      a randomized controlled trial.
AB  - The analgesic properties of salmon calcitonin for the treatment of atypical
      facial pain (AFP) were investigated. An initial open-label trial of salmon
      calcitonin in subjects with refractory AFP was followed with a randomized, double
      blind, placebo-controlled crossover trial of salmon calcitonin in the management
      of AFP. Salmon calcitonin (100 IU in 1 mL saline) was administered in an open
      label fashion to 13 subjects with refractory AFP five times per week for 6 weeks.
      In the subsequent randomized investigation, salmon calcitonin (100 IU in 1 mL
      saline) or placebo (1 mL saline) was delivered three times per week for 3 weeks,
      with a 1-week washout prior to crossover. The percentage of subjects dropping out
      (57%) exceeded that reported in other pain studies using calcitonin. Therefore,
      it was imperative to halt the study for ethical reasons. There was no difference
      in outcome measures (P > .05) in subjects administered either active drug or
      placebo, and a high incidence of side effects led to dropout in subjects taking
      salmon calcitonin. Although salmon calcitonin may have analgesic properties, it
      is not efficacious for AFP, largely because of the side effects.

PMID- 9161236
TI  - Pain and the quality of life in patients referred to a craniofacial pain unit.
AB  - Although there are reasons to believe that temporomandibular disorders and other
      facial pain conditions would have a major impact on the quality of patients'
      lives, only a small number of studies have attempted to address this in a
      systematic way. In this study, data on pain and its consequences were assessed
      for 121 patients making their first visit to a craniofacial pain research unit.
      The extent to which musculoskeletal and neurologically based facial pain
      compromised the quality of life was measured using the Oral Health Impact
      Profile, a recently developed index of the functional and psychosocial outcomes
      of oral conditions. The data indicated that facial pain had a substantial impact
      on daily life and that its most common outcomes were psychologic. When compared
      with a nonpain population, the extent of this impact was striking. There was a
      four-fold increase in functional problems such as difficulty chewing foods and a
      nine-fold increase in reports of depression. As anticipated, scores on the Oral
      Health Impact Profile were associated with the characteristics of the pain and
      diagnostic subgroups.

PMID- 9161238
TI  - Effects of 5 days of repeated submaximal clenching on masticatory muscle pain and
      tenderness: an experimental study.
AB  - The hypothesis of this short-term study was that repeated episodes of clenching
      at submaximal bite force levels can induce a progressive increase in pain and
      tenderness in masticatory muscles. On each day for 5 consecutive days, 10 women
      clenched on a bite force transducer for 15 minutes at 25% of their maximal bite
      force. The development of pain, tenderness, and unpleasantness in the masticatory
      muscles was evaluated with use of 10-cm visual analog scales (VAS) and the McGill
      Pain Questionnaire (MPQ). Pain detection thresholds (PDT) and pain tolerance
      thresholds (PTT) to percutaneous pressure stimuli were measured in the masseter
      and anterior temporalis muscles. Maximal voluntary bite force to brief clenches
      were assessed. The results showed moderate levels of pain (mean +/- SE; 5.3 +/-
      1.0), tenderness (5.2 +/- 1.0), unpleasantness (5.8 +/- 0.8), and MPQ scores
      (16.4 +/- 4.9) immediately after the submaximal clenching task on the first day.
      The following days, the clenching tasks did not increase these scores; in
      contrast, there were significant decreases on day 5 in both pain intensity (
      49.8% +/- 14.6%), tenderness (-46.1% +/- 14.2%), unpleasantness (-50.4% +/-
      8.5%), and MPQ scores (-45.8% +/- 13.3%) (P < .05) when compared to day 1. The
      clenching procedure failed to induce a progressive increase in pain and
      tenderness in the masticatory muscles during 5 days. None of the evaluated
      parameters from this study suggested the start of a vicious cycle.

PMID- 9161237
TI  - The influence of cutaneous tissue afferents on masticatory pain-pressure
      thresholds.
AB  - Pain-pressure thresholds are routinely used in orofacial pain research to record
      tenderness in masticatory muscles. This method is employed to stimulate deep
      tissue afferents, which are thought to be at least partially responsible for pain
      in temporomandibular disorders. Like other psychophysical measurements, however,
      this technique must stimulate cutaneous tissues before stimulating deeper
      tissues. This study examined 39 asymptomatic volunteers to quantify the effect of
      cutaneous sensory afferents on pain-pressure thresholds. In a randomized, double
      blind fashion, pain-pressure thresholds were recorded at four facial sites before
      and after subjects received intradermal local anesthetic or a dry needle stick.
      Pain-pressure thresholds were significantly elevated after local anesthetic (P <
      .0001), suggesting that cutaneous tissues contribute significantly to the pain
      pressure threshold. The authors discuss potentially important roles of cutaneous
      tissues in the assessment of deeper tissues and offer two theories of how the
      skin may be an important link in the assessment of temporomandibular disorders.

PMID- 9161239
TI  - Assessment of pain (distribution and onset), Symptoms, SCL-90-R Inventory
      responses, and the association with infectious events in patients with chronic
      orofacial pain.
AB  - A visual analog pain scale and scalar responses to 13 pain/symptom indicator
      Symptom Checklist-90-Revised (SCL-90-R) questions were used to assess symptom
      prevalence and pain severity in 43 chronic orofacial muscle pain patients and 40
      control subjects. The orofacial muscle pain group reported pain in an axial
      skeletal distribution; neurocognitive, gastrogenitourinary, and musculoskeletal
      symptoms; infectious events at or preceding onset; similar symptoms in sexual
      partners; and low prevalence of trauma. Sudden onset was reported by 30.2% of
      pain patients. Strong associations were found between chronic orofacial muscle
      pain and (1) onset-related infectious-like events (67.4%); (2) a higher
      prevalence of history of respiratory and gastrogenitourinary infectious events;
      and (3) high prevalences of similar pain symptoms in long-term sexual partners.
      The SCL-90-R somatization scores (> 62) had a higher prevalence in the chronic
      pain group. No prevalence differences or associations with pain/symptom
      indicators were found for depression or anxiety dimension scores. These data
      suggest that patients with recurrent systemic infectious events have a higher
      prevalence of reporting of chronic orofacial muscle pain compared with control
      subjects, and these infectious events are associated with the onset of chronic
      orofacial muscle pain in 67% of patients.

PMID- 9161240
TI  - A multiple stepwise logistic regression analysis of trauma history and 16 other
      history and dental cofactors in females with temporomandibular disorders.
AB  - The simultaneous contribution of 11 occlusal factors, dental attrition severity,
      orthodontic history, trauma (motor vehicle accident [MVA] and non-MVA), and age
      in defining two independent large populations of females diagnosed with five
      mutually exclusive temporomandibular disorders was tested through multiple
      stepwise logistic regression analysis. Non-MVA trauma was significant in both
      groups in defining disc displacement (DD) with and without reduction, and
      osteoarthrosis (OA) (both primary and following DD). Anterior open bite was also
      a significant factor in defining OA in both groups. Much smaller contributions
      were also made by missing teeth in one of the populations with OA following DD,
      and by retruded contact position-intercuspal position slide lengths and overjet
      in one of the primary OA populations. Motor vehicle accident trauma was
      significant in defining myofascial pain (MP) in both populations, and
      laterotrusive attrition mildly defined MP in one population. Only a minority of
      total variance was explained: 6% to 8% of DD with reduction; 10% to 14% of DD
      without reduction; 11% to 20% of OA following DD; 17% to 38% of primary OA; and
      4% to 10% of MP. Non-MVA trauma was the major defining feature of the
      temporomandibular joint intracapsular disorders, and MVA trauma explained a very
      small percentage of the MP patients. Implications are discussed and
      recommendations are made for future research.

PMID- 9161242
TI  - Dollars or discretion?

PMID- 9161241
TI  - Variability in the quantification of abrasion on the Bruxcore device.
AB  - The rate of abrasion of dental surfaces during short periods of time is difficult
      to measure clinically, but one quantifiable method is the use of the Bruxcore
      bruxism monitoring device. The aim of this study was to estimate the
      interobserver and intraobserver variation in the Bruxcore system using different
      reading methods. Fifteen volunteers used individually fabricated Bruxcore devices
      during 4 consecutive nights, and this procedure was repeated after 6 weeks. The
      abraded areas of the 30 Bruxcore devices were measured by two observers on two
      occasions and with three methods: microscope without a reference scale;
      microscope with a reference scale; and a computer-aided system. Intraobserver
      variation was small (5%), but interobserver variation was statistically
      significant for all three methods. The computer-aided system was superior to the
      other two methods. The interaction between Bruxcore values and observers was
      statistically significant for the microscope methods but not for the computer
      method. This was a desired property, indicating stability of the computer-aided
      method over the range of Bruxcore values observed. Small measurement errors,
      independent of the size of the measurements, can be expected using a trained
      observer and a computer-aided method for reading the Bruxcore bruxism monitoring
      device.

PMID- 9161243
TI  - Need before greed.

PMID- 9161244
TI  - Recent trends in esthetic restorations for posterior teeth.
AB  - The increase in the demands made by patients for esthetic or metal-free
      restorations, together with the ever-growing interest shown by the dental
      profession for tooth-colored materials and techniques, led to the current
      development of posterior adhesive restorations. This paper reviews critical
      elements such as adhesion to dental hard tissues as well as current properties of
      bases/liners, filling materials, and luting materials. A rationale for the
      successful use of currently available restorative systems is presented.

PMID- 9161246
TI  - Adhesive restorations with amalgam: guidelines for the clinician.
AB  - The adhesive amalgam restoration technique combines the good properties of
      amalgam with the principles of tooth structure preservation and marginal seal
      inherent to adhesive materials. In spite of lack of longitudinal data, results of
      early clinical and laboratory tests are encouraging. If the present research is
      substantiated by clinical confirmation of their results, bonded amalgam
      restorations will become routine. The purpose of this article is to present a
      brief literature review on adhesive amalgam restoration and to introduce
      guidelines for its use.

PMID- 9161245
TI  - Tissue integration of one-stage implants: three-year results of a prospective
      longitudinal study with hollow cylinder and hollow screw implants.
AB  - Tissue integration of one-stage, nonsubmerged ITI implants over a 5-year period
      is documented. Fifty-four implants were placed in 38 partially edentulous
      patients. No implants had detectable mobility after a healing phase of at least 3
      months, and there were no clinical signs of peri-implant infection. Radiographs
      revealed no peri-implant radiolucencies and all implants were in favorable
      positions for fixed prosthetic restorations. Following completion of the
      prosthetic treatment, all patients were placed in 3-month oral hygiene recall
      programs. Annual dental examinations included evaluation of each implant
      according to fixed criteria. Three years after implant placement, 51 of 53
      implants (96.2%) were evaluated as successful (one patient was lost to the
      study). Acute peri-implant infections were associated with two implants; both
      were classified as late failures. The results demonstrated that one-stage
      transgingivally healing ITI implants integrate dependably in the tissue and that
      successful tissue integration can be maintained for at least 3 years.

PMID- 9161247
TI  - Improving interproximal access in direct provisional acrylic resin restorations.
AB  - A new technique that improves interproximal access in direct provisional acrylic
      resin restorations is presented. In this technique a clear Mylar strip is placed
      interproximally and lifted off with an overimpression prior to the beginning of
      the tooth preparation procedures. Preparation of the tooth and fabrication of the
      provisional restorations then continues in the usual direct manner. The Mylar
      strip, now embedded in the overimpression, becomes incorporated as a separator
      between the adjacent provisional restorations. The acrylic resin provisional
      restorations are easily snapped apart and finished individually. The advantages
      of the technique and the need for marginal perfection around the full perimeter
      of the tooth are also discussed.

PMID- 9161248
TI  - Early treatment considerations for oligodontia in ectodermal dysplasia: a case
      report.
AB  - Two brothers diagnosed with ectodermal dysplasia were treated for 5 years during
      their mixed-dentition periods for problems arising from absence of teeth
      (oligodontia) and abnormally formed teeth. An individualized approach to
      restorative and prosthodontic management allowed dynamic and evolving treatment
      attuned to their concern about their appearance.

PMID- 9161249
TI  - Electronic anesthesia versus topical anesthesia for the control of injection
      pain.
AB  - The ability of a dental transcutaneous electronic nerve stimulator to control
      pain from injection of local anesthesia was compared to the pain-controlling
      ability of topical anesthesia. Two maxillary infiltration injections were
      completed on 21 patients, one injection after electronic anesthesia, the other
      after topical anesthesia. Patients reported the level of pain caused when the
      needle pierced their tissue and the solution was injected and their overall
      evaluation of the injection. No difference was reported for piercing of the
      tissue; however, the level of pain was very low. Significantly less pain was
      reported for the injection of local anesthesia solution and the overall
      evaluation of the injection was more favorable when electronic anesthesia was
      used. The patients preferred the electronic technique three to one over the
      topical anesthesia.

PMID- 9161250
TI  - Traumatic injuries to permanent incisors: a case report.
AB  - A case report involving traumatized maxillary incisors is presented. The right
      central and lateral incisors were avulsed by direct trauma and were not found.
      The left central incisor was luxated and the left lateral incisor was fractured
      at the coronal portion. Placement of implant fixtures was selected as treatment
      to prevent resorption of alveolar bone and to maintain the integrity of intact
      adjacent teeth. The right incisors were replaced with two osseointegrated
      implants. The left central incisor was endodontically treated and a cast post and
      core was bonded into the root canal. All three of these teeth were restored with
      porcelain-fused-to-metal crowns. A composite resin restoration was placed on the
      left lateral incisor. The esthetic and functional results were satisfactory.

PMID- 9161251
TI  - An introduction to forensic dentistry.
AB  - Dental science has much to offer law enforcement agencies in the detection and
      solution of crime. The permanent teeth develop throughout the first two decades
      of life, and physiologic variations, pathoses, and the effects of dental therapy
      may be recorded in the hard tissues of the remaining dentition throughout life
      and beyond. It is the role of the forensic dentist to extract this information
      and use it in the identification of the unknown body. The teeth may also be used
      as weapons and, under certain circumstances, may leave information as to the
      identity of the biter. Analysis of bite marks is the second major responsibility
      of the forensic dentist. The general practitioner has a major role to play in
      providing the accurate dental records on which much of forensic activity is
      based.

PMID- 9161253
TI  - Peer review--it should mean something.

PMID- 9161252
TI  - The ectrodactyly-ectodermal dysplasia-clefting syndrome: a literature review and
      case report.
AB  - Ectrodactyly, atypical anhidrotic ectodermal dysplasia, and cleft lip and palate
      are the principal manifestations of ectrodactyly-ectodermal dysplasia-clefting
      syndrome. Intraorally, the common manifestations of the syndrome are hypodontia,
      enamel hypoplasia, and generalized microdontia. In addition, the patient may
      suffer from xerostomia and have a deeply fissured tongue. The oral mucosa
      appears, in some patients, to have an increased susceptibility to candidiasis.
      This case report describes a patient who exhibits many of the manifestations of
      the syndrome and explains ways in which many of the anomalies of the dentition
      can be esthetically and functionally corrected.

PMID- 9161254
TI  - Allergies to dental materials.
AB  - Allergies related to dentistry generally constitute delayed hypersensitive
      reactions to specific dental materials. Although true allergic hypersensitivity
      to dental materials is rare, certain products have definite allergenic
      properties. Extensive reports in the literature substantiate that certain
      materials cause allergies in patients, who exhibit mucosal and skin symptoms.
      Currently, however, neither substantial data nor clinical experience
      unequivocally contraindicate the discontinuance of any of the materials, which
      include dental amalgam and nickel- and chromium-containing metals. The dentist
      forms a vital link in the team approach to the differential diagnosis of
      allergenic biomaterials that elicit symptoms in a patient, not only intraorally,
      but also on unrelated parts of the body.

PMID- 9161255
TI  - Hydrothermal ceramic for porcelain-fused-to-metal crowns: an initial experience
      report from clinical practice.
AB  - The development of hydrothermal ceramics was an important requirement for fusing
      hydrolysis-resistant ceramics to precious metal alloys with low melting interval.
      Clinical findings since 1992 confirm the wide range of application of these metal
      ceramic restorations in dentistry. Initial problems concerning temperature
      regulation of the ceramic ovens were rectified by checking and adjusting them for
      lower sintering temperatures. The golden yellow color is only one advantage of
      the ceramic-veneered alloy. Other advantages include its nonporous, smooth
      surface, translucence, and suitability for use in all types of dental
      restorations and reconstructions. Hydrothermal ceramic veneers thus can help to
      substantially reduce the number of different alloys used in a patient's mouth.

PMID- 9161256
TI  - Planning fixed partial dentures for severely misaligned abutments.
AB  - When the abutment teeth of a fixed partial denture are severely misaligned,
      insertion of the prosthesis becomes more difficult. Some of the methods
      traditionally recommended to overcome the problems associated with this situation
      are examined. One design that simplifies treatment and improves the prosthesis is
      suggested.

PMID- 9161257
TI  - Two applications of transmucosal milled ceramic in implantology: preliminary
      clinical examples.
AB  - Two new implant systems, the Compound Implant and the TFM coping/abutment, are
      based on the association of titanium in the infrabony portion and a dense milled
      ceramic in the transgingival portion. The coating of zirconium ceramic on the
      transmucosal collar of the Compound Implant is particularly indicated for a
      single-stage surgical implant technique. The isolating properties and the high
      wettability of this material favor gingival healing and reduce the accumulation
      of plaque; the esthetic collar permits a supragingival or juxtagingival cervical
      margin favoring plaque control and minimizing the consequences of tissue
      remodeling. The hardness of the ceramic also allows it to undergo conventional
      prophylaxis with ultrasonic scalers without alteration of its surface quality. In
      addition to the above-mentioned advantages, the TFM coping/abutment, an implant
      prosthesis connector in alumina ceramic, for use in a two-stage technique,
      provides electrogalvanic isolation of the implant, and personalized abutment
      preparation allows for simplified fabrication of an implant-supported prosthesis.

PMID- 9161258
TI  - Electronic and local anesthesia: a clinical comparison for operative procedures.
AB  - The comfort on administration and effectiveness of electronic and local
      anesthesia for operative procedures, as perceived by clinicians and patients,
      were compared based on a 5-point Lickert scale, and a survey to solicit patient's
      feedback on the use of electronic anesthesia was conducted. Thirty patients, who
      required restorations on similar teeth bilaterally, and 10 clinicians were
      involved in the study. The two teeth in each patient were randomly restored under
      either electronic or local anesthesia. Administration of electronic anesthesia
      was perceived to be significantly more comfortable than that of local anesthesia,
      by both clinicians and patients. Local anesthesia was perceived to be
      significantly more effective by both evaluator groups, but 93.3% of the patients
      still preferred electronic anesthesia and would use it again. Minor after effects
      in some patients included redness of skin and briefly lingering sensation. All
      patients found electronic anesthesia easy to use, and most of the patients
      (93.3%) thought that the system was good to excellent.

PMID- 9161259
TI  - Treatment of severe physiologic gingival pigmentation with free gingival
      autograft.
AB  - Melanin is normally found in the skin of all people, and normal pigmentation of
      the intraoral tissues is a relatively frequent finding. The highest rate of
      gingival pigmentation has been observed at the incisors. Until recently, however,
      very little attention has been paid to the esthetic treatment of severe gingival
      pigmentation. To answer the cosmetic demand for a pleasing smile, pigmented
      gingiva was replaced with an unpigmented free gingival autograft in 10 patients.
      At least two areas in each patient were grafted. In all 10 areas in which the
      recipient site received full-thickness bed preparation, no evidence of
      repigmentation was found after 4.5 years. Of the 10 areas that received partial
      thickness bed preparation, only one exhibited repigmentation (after 1 year).

PMID- 9161260
TI  - Color differences between resin composites and shade guides.
AB  - The color of manufacturers' shade guides was compared with the color of the
      actual resin composites. Five light-activated resin composite products were
      evaluated. Resin specimens and shade guides of same thickness were measured with
      a spectrophotometer. Color differences (delta E* values) were more than
      perceptible in all products. The mean delta E* values were least in Z100 and
      greatest in Herculite XR. Generally, the L* and b* values of the shade guides
      were higher than those of the resin composites. Some colors showed color
      differences greater than the acceptable level.

PMID- 9161262
TI  - "When life knocks at the door no one can wait".

PMID- 9161261
TI  - A clinically viable index for quantifying denture plaque.
AB  - A denture plaque index using the dye disclosing method was evaluated in 24
      patients with Type II denture stomatitis and 17 control subjects with healthy
      palatal mucosa. Patients with denture stomatitis had statistically significantly
      higher plaque scores than did controls, indicating a quantitative increase in
      denture plaque in patients with denture stomatitis. When this plaque index was
      tested by two examiners for intraexaminer and interexaminer reproducibility, it
      yielded a 92% to 96% reproducibility. The plaque index used in this study seems
      to satisfy the criteria for an ideal clinical index: It is simple, reliable,
      reproducible, and economical and can be carried out in the shortest possible time
      in a clinical setting.

PMID- 9161263
TI  - The quintessential sealant?
AB  - A method of placing a reinforced resin-bonded sealant is described. When the
      beneficial properties of resin-bonded sealants are combined with those of
      preventive resin restorations, the outcome is perhaps the "quintessential
      sealant."

PMID- 9161264
TI  - Posterior resin composite restorations: a new technique.
AB  - A new technique for the performance of resin composite direct restorations on
      posterior teeth is presented. A clear acrylic resin matrix, fabricated prior to
      the preparation of the occlusal and proximal surfaces, is employed. The matrix
      allows the fast and accurate reproduction of the anatomic details from the
      original occlusal surface of the tooth, as well as the marginal ridges in the
      case of Class II (occlusoproximal) restorations. Advantages and limitations of
      the procedure are discussed.

PMID- 9161265
TI  - Use of resin-bonded partial coverage ceramic restorations to treat incomplete
      fractures in posterior teeth: a clinical report.
AB  - The objective of restorative treatment of teeth with incomplete fractures is to
      minimize flexure of the compromised cusps to prevent propagation of the crack.
      These goals can be addressed with resin-bonded posterior ceramic restorations,
      but long-term integrity rests on the efficiency of the restoration's bond to the
      dental hard tissues. Success is dependent on diligent operative performance
      throughout the entire procedure. Some tips for achieving successful preparation,
      provisionalization, and partial-coverage restoration of the incompletely
      fractured posterior tooth are discussed.

PMID- 9161266
TI  - An injection technique for generating direct resin post and core patterns.
AB  - An injection technique can be used to rapidly generate direct post and core
      patterns with autopolymerizing acrylic resin. The technique uses an
      autopolymerizing acrylic resin, a serrated plastic pin, and a syringe with a
      disposable needle tube and plug to inject acrylic resin into the root canal. The
      technique is simple, accurate, and faster than the bead-brush technique and
      eliminates some of its shortcomings.

PMID- 9161267
TI  - A new design for all-ceramic resin-bonded fixed partial dentures.
AB  - After 7 years of clinical experience, the alumina ceramic, In-Ceram, can be
      regarded as a well-proven material for all-ceramic crowns. Because of its high
      strength, this material can also be used for small all-ceramic fixed partial
      dentures. First attempts at using this material for resin-bonded prostheses
      revealed a high failure rate. The aim of this article is to present a new
      preparation design for all-ceramic resin-bonded fixed partial dentures that
      allows fabrication of highly esthetic and also tooth-saving adhesive prostheses.
      Clinical results over a period of 4 years revealed that they are strong enough to
      replace anterior teeth. Nevertheless, positive long-term clinical results are
      necessary before a general recommendation can be given for this kind of
      prosthesis.

PMID- 9161268
TI  - An alternative approach to replacement of a congenitally missing maxillary
      central incisor: a case report.
AB  - The prosthetic replacement of a missing central incisor is described. The left
      anterior teeth were transformed, through the placement of laminate veneers, to
      simulate a complete dentition; the lateral incisor was made to look like a
      central incisor, the canine like a lateral incisor, and the first premolar like a
      canine. The right central and lateral incisors were also restored for esthetic
      purposes. The most important factors associated with this type of case are
      discussed in detail.

PMID- 9161269
TI  - Desquamative gingivitis: a clinical, histopathologic, and immunologic study.
AB  - Desquamative gingivitis is believed to be a clinical sign of certain
      mucocutaneous diseases rather than a distinct pathologic entity. The prevalence
      of desquamative gingivitis was studied in a group of patients with the most
      common mucocutaneous diseases. Of 414 patients with pemphigus vulgaris, mucous
      membrane pemphigoid, or oral lichen planus, 49 (11.8%) exhibited gingival lesions
      in the form of desquamative gingivitis. Desquamative gingivitis was most
      prevalent in the patients with mucous membrane pemphigoid (41.6%) followed by
      those with pemphigus vulgaris (9.1%). Other clinical characteristics, as well as
      histopathologic and immunohistochemical findings, that aid in early diagnosis are
      presented.

PMID- 9161270
TI  - Clinical evaluation of a samarium compound filter and E-speed film.
AB  - Producing radiographs of good diagnostic quality while keeping the dose as low as
      possible is the goal of the dental radiographer. Rare earth compound filters
      reduce the dose, but few clinical studies have evaluated the diagnostic yield.
      The diagnostic quality of a samarium compound filter used with E-speed film was
      compared with that of a conventional aluminum filter used with E-speed film.
      Bitewing projections with the test and standard filters were exposed for 39
      patients. Agreement was evaluated with kappa statistics. The results indicated a
      substantial level of agreement between the two filter types. The combination of
      samarium compound filter and E-speed film appears to be a good mechanism for
      achieving dose reduction without compromising the diagnostic yield of the film.

PMID- 9161271
TI  - Three-year clinical effectiveness of four total-etch dentinal adhesive systems in
      cervical lesions.
AB  - A 3-year follow-up clinical trial of two experimental Bayer total-etch adhesive
      systems and two commercial total-etch systems. Clearfil Liner Bond System and
      Scotchbond Multi-Purpose, was conducted to evaluate their clinical effectiveness
      in Class V cervical lesions. Four hundred twenty abrasion-erosion lesions were
      restored randomly using the four adhesive systems. There were two experimental
      cavity designs, in which the adjacent enamel margins either were or were not
      beveled and acid etched. Clearfil Liner Bond System and Scotchbond Multi-Purpose
      demonstrated high retention rates in both types of cavity design at 3 years. The
      two experimental Bayer systems scored much lower retention rates in both cavity
      designs at 3 years. None of the systems guaranteed margins free of microleakage
      for a long time. At 3 years, superficial, localized marginal discolorations were
      observed, the least for Clearfil Liner Bond System, followed by Scotchbond Multi
      Purpose and the two experimental systems. Small marginal defects were recorded at
      the cervical dentin and the incisal enamel margin. Retention of Clearfil Liner
      Bond and Scotchbond Multi-Purpose appears to be clearly improved over earlier
      systems, but marginal sealing remains problematic. The two Bayer systems were
      found to be clinically unreliable.

PMID- 9161272
TI  - Management of developmental asymmetrical facial growth.
AB  - Several aspects of the management of developmental asymmetrical facial growth are
      addressed. The abnormality is further defined. Methods of examination and
      assessment of records are discussed. A complicating factor has been the adoption
      of too many classification systems. With three-dimensional imaging techniques
      (computed tomography scan and stereophotography) great advancement has been made
      in efforts at describing the range of variation. Hemifacial microsomia patients
      are best treated in multidisciplinary centers by competent specialists with the
      necessary expertise and skills. The procedure followed in the craniofacial center
      in Rotterdam is described and discussed in relation to current treatment
      strategies. The success of the treatment of the asymmetrical facial growth
      depends on the original abnormality, on secondary abnormal development, and on
      orthodontic and surgical intervention. International cooperation is necessary to
      compile sufficient statistical data for a scientific evaluation of treatment
      results and to improve the effectiveness and the efficiency of treatment.

PMID- 9161273
TI  - Treatment strategies for midline discrepancies.
AB  - Midline discrepancies are among the most complex and commonly seen problems in
      clinical orthodontics. Skeletal, soft tissue, and dentoavleolar asymmetries may
      be present alone or in combination in a patient who has noncoincident midlines.
      Due to the multifactorial etiology of midline discrepancies, a thorough
      understanding of the components that may contribute to the problem is essential
      for a correct diagnosis. The treatment mechanics that are derived from the
      treatment plan must be biomechanically oriented in order to achieve the desired
      results without the introduction of adverse side effects. This article discusses
      strategies to correctly diagnose and treat patients with significant midline
      asymmetries.

PMID- 9161274
TI  - Alternative nonsurgical strategies to treat complex orthodontic problems.
AB  - Patients whose vertical discrepancies are best corrected with both orthodontics
      and surgery can be placed into two distinct categories. The first category is the
      group of patients who have short posterior facial heights in conjunction with
      excessive anterior facial heights. The second category is the group of patients
      who have the opposite problem, i.e., excessive posterior facial heights and
      decreased anterior facial heights. Both of these types of malocclusions can best
      be treated with a combination of orthodontics and surgery. Alternative treatment
      for these "outer limits" patients require a thorough differential diagnosis,
      selection of appropriate force systems, and an understanding that nonsurgical
      treatment will result in compromises. Although these compromises must be accepted
      these patients can expect treatment results that are esthetically pleasing,
      highly acceptable for the teeth and supporting tissues, functional, and
      reasonably stable if a careful differential diagnosis is followed with treatment
      that uses precise space management with sequential directional force application.

PMID- 9161275
TI  - Three-dimensional diagnosis and management of Class II malocclusion in the mixed
      dentition.
AB  - Class II malocclusion is a commonly observed problem, occurring in about one
      third of the United States population. The numerous treatment approaches that
      have been advocated to treat this malocclusion presumably produce differing
      treatment effects within the skeletal, dentoalveolar, and soft tissue components
      of the face. In the first section of this article, the three-dimensional
      components of Class II malocclusion are described, with transverse maxillary
      discrepancy, mandibular skeletal retrusion, and increased lower anterior facial
      height observed as common findings in a mixed dentition sample of Class II
      subjects. Second, the literature concerning two seemingly diverse treatment
      methods (extraoral traction and functional jaw orthopedics) is reviewed in
      detail. Last, cephalometric data are presented from a retrospective clinical
      study and is used to evaluate the treatment effects produced by cervical traction
      and the FR-2 appliance of Frankel in comparison with an untreated sample of mixed
      dentition Class II patients. The results of this study indicated that although
      both skeletal and dentoalveolar components of Class II, Division 1 malocclusion
      were altered in the Class I direction by either a facebow or a Frankel appliance,
      these two appliance systems accomplished the correction in dramatically differing
      ways. Cervical traction affected the skeletal and dentoalveolar components of the
      maxilla and mandible, whereas the FR-2 appliance had less of an effect on
      maxillary and dentoalveolar components and a greater effect on mandibular length.
      Thus, these two treatment modalities produce decidedly different treatment
      effects in patients with Class II malocclusions.

PMID- 9161277
TI  - Managing complex orthodontic problems: the use of implants for anchorage.
AB  - Today implants are commonly used to replace missing teeth in partially edentulous
      adult orthodontic patients. Because these patients are missing teeth, orthodontic
      mechanics may be complicated or often impossible because of insufficient
      anchorage. In these situations, it may be feasible to use the implant initially
      as an orthodontic anchor to facilitate complex tooth movement and secondarily as
      an abutment for a crown or fixed prosthesis. This article will discuss the
      ramifications and requirements for using implants as anchors and abutments in
      adult orthodontic patients.

PMID- 9161276
TI  - Orthodontic management of the short face patient.
AB  - A short lower face may accompany various types of malocclusions depending on the
      structural etiology. Because most cephalometric analyses focus on the
      anteroposterior plane of space, they are often insufficient in diagnosing a
      significant vertical dysplasia. This article describes a cephalometric analysis
      that examines not only the vertical proportions of the face, but the various
      anatomical features that contribute to the dysplasia. Diagnosis is further
      enhanced by evaluating the facial profile with the mandible postured at various
      amounts of opening, suggesting the degree of vertical discrepancy. Traditional
      orthodontic therapy corrects the associated malocclusion but is usually
      ineffective in changing inherent facial proportions. However, several orthopedic
      methods have shown the ability to increase lower facial height when used in
      combination with nonextraction orthodontic mechanotherapy. Adults with short
      faces require a combination of orthodontics and orthognathic surgery. The Class
      II malocclusion can usually be managed by surgically advancing the mandible with
      the curve of Spee maintained. In cases of vertical maxillary deficiency, the
      LeFort I osteotomy with inferior repositioning provides the spatial correction
      that is needed. Two cases are presented to illustrate the cephalometric and
      facial analyses used in diagnosis, as well as the common surgical procedures to
      manage the short face patient.

PMID- 9161278
TI  - Clinical implications of recent orthodontic-periodontic research findings.
AB  - During the past 15 years, advances in basic science related to periodontal
      biology, and clinical trials on prevention and treatment of periodontal disease,
      have dramatically changed many treatment concepts in periodontics. The most
      pertinent information for orthodontic practice from these studies is summarized.
      Also, recent advances in orthodontics, particularly regarding bonding of
      attachments to artificial tooth surfaces and improved long-term stabilization of
      orthodontic treatment results in adults by means of bonded lingual retainers have
      significant implications. This article outlines how recent research information
      from both dental specialties may be used by orthodontists to improve treatment
      planning, clinical management, and retention of their adult and elderly patients
      in whom different malocclusions are complicated by moderate to advanced
      periodontal destruction.

PMID- 9161279
TI  - Current concepts in diagnosis and treatment of periodontitis.
AB  - This article describes some areas of periodontal research and current opinions
      regarding detection of disease progression, as well as risk indicators and risk
      factors associated with disease progression. Longitudinal probing of periodontal
      attachment level is considered the gold standard for detection of disease
      activity although there are problems with this concept. Digital subtraction
      radiography can assist in the detection of minor changes of alveolar bone height
      and density. Risk factors such as composition of subgingival plaque and gingival
      crevicular fluid, as well as the effect of smoking are discussed. Adjunctive
      treatment with both antibiotics and nonsteroidal anti-inflammatory drugs,
      systemic or local, seems to be helpful in some forms of disease. Immunization to
      prevent colonization of tooth surfaces and pockets by periodontal pathogens does
      not seem to be feasible in the near future.

PMID- 9161280
TI  - Esthetics: the orthodontic-periodontic restorative connection.
AB  - As we complete the 20th and progress into the 21st century, orthodontists
      worldwide are experiencing a gradual but significant change in their practices.
      The number of adult patients has increased substantially. Although adults
      cooperate better than adolescents, they present a different set of challenges for
      the orthodontist. Adults may have worn or abraded teeth, uneven gingival margins,
      missing papillae, and periodontal bone loss, all of which can jeopardize the
      esthetic appearance of the teeth after bracket removal. This article will discuss
      the solutions for managing these challenging orthodontic-periodontic-restorative
      situations to produce a more ideal esthetic result.

PMID- 9161281
TI  - The significance of bone in periodontal disease.
AB  - Although the connective tissue attachment represents the key issue in periodontal
      health or disease and in periodontal therapy, the assessment of alveolar bone
      changes renders valuable indirect evidence for periodontal stability, progression
      of disease, or repair mechanisms. In periodontal disease bacterial products
      trigger host cells to release mediators, which may imbalance the steady state
      between resorption of bone and apposition of osteoid. Modulation of the hosts
      prostaglandin or interleukin-I synthesis by drug therapy could support the
      antimicrobial concept of periodontal therapy. Cross-sectional and long-term
      assessments of alveolar bone have been used to estimate the progression rate of
      periodontal disease. Inherent limitations of bone assessments in radiographs have
      to be considered when drawing conclusions from measurements that represent
      remodeling in periodontal lesions after therapy. Both bone quantity and quality
      seem to be of secondary importance with respect to the progression of disease, as
      well as response to therapy. Other risk factors that affect the microbial ecology
      and/or the hosts immune system seem to be the primary determinants for the
      periodontal health status.

PMID- 9161282
TI  - Guided tissue regeneration associated with orthodontic therapy.
AB  - Guided tissue regeneration (GTR) to enhance genuine new periodontal attachment
      may improve preorthodontic conditions for moving teeth into infrabony defects or
      for vertical movements of teeth with reduced bone support. The possible benefits
      of GTR for combined periodontal/orthodontic therapy are discussed and
      substantiated with preliminary experimental findings.

PMID- 9161283
TI  - Mucogingival considerations in orthodontic treatment.
AB  - Alterations in the mucogingival complex will occur during orthodontic tooth
      movement, but these are independent of the apico-coronal width (height) of the
      gingiva. The integrity of the periodontium can be maintained during orthodontic
      therapy also in areas that have only a minimal zone of gingiva. In terms of
      changes in the position of the soft tissue margin and in gingival dimensions, the
      important factors to consider are the direction of the tooth movement and the
      bucco-lingual thickness of the gingiva. Lingual tooth movement will result in an
      increased bucco-lingual thickness of the tissue at the facial aspect of the tooth
      which results in coronal migration of the soft tissue margin (decreased clinical
      crown height). Facial tooth movement, on the other hand, will result in a reduced
      bucco-lingual tissue thickness and thereby a reduced height of the free gingival
      portion and an increased clinical crown height. The risk for development of
      recession type defects in conjunction with orthodontic tooth movement is present
      only if the tooth has been moved out of the alveolar bone housing, ie, when an
      alveolar bone dehiscence has been created.

PMID- 9161284
TI  - Infrabony pockets and reduced alveolar bone height in relation to orthodontic
      therapy.
AB  - Experimental animal studies have shown that orthodontic movement of teeth into
      infrabony pockets may be detrimental to the periodontal attachment. After
      elimination of subgingival plaque infection in the experimental animals, no
      additional loss of connective tissue attachment occurred. An experimental model
      has shown that a tooth with normal periodontal support can be orthodontically
      moved into an area of reduced bone height with maintenance of height of
      connective tissue attachment level and alveolar bone support. The results from
      these experimental studies have been tested clinically.

PMID- 9161285
TI  - The incidence, classification, etiology, and embryology of oral clefts.
AB  - There are numerous problems encountered among individuals with a cleft lip and/or
      cleft palate. Addressing these problems necessitates a multidisciplinary
      approach, requiring a team of experts to facilitate care for these individuals.
      Dentists play a vital role on the team. An orthodontist, pediatric dentist, oral
      maxillofacial surgeon, and prosthodontist usually represent the dental members of
      the team. The success of this team depends on expertise within each discipline
      but also depends on each member having a broad base of knowledge in general about
      oral clefts. An understanding of other disciplines and how they approach the
      treatment of oral clefts is important for each team member. Also, each team
      representative should appreciate the need to understand the causes of oral
      clefts, how clefts develop in utero, how various populations are affected, and
      how to recognize and classify an oral cleft. It is difficult to communicate
      effectively within the team if we fail to recognize the importance of expanding
      our knowledge to include other aspects of oral clefts beyond treatment
      perspectives. This article provides the orthodontist with basic information as it
      relates to the etiology of oral clefts (ie, genetics, teratogens, and medical
      conditions), the demographics and incidence of oral clefts, the embryology and
      classification of clefts.

PMID- 9161286
TI  - A comparison of treatment results in complete bilateral cleft lip and palate
      using a conservative approach versus Millard-Latham PSOT procedure.
AB  - Conservative non-presurgical orthopedic treatment in complete bilateral cleft lip
      and palate (CBCLP) cases were compared with those treated will the Millard-Latham
      (M-L) method, which involves the presurgical mechanical retraction of the
      protruding premaxilla using pinned palatal appliances. In conservatively treated
      cases, a head bonnet with an external elastic is sometimes used before surgical
      lip closure to ventroflex the premaxilla thereby reducing tension at the surgical
      sites. The M-L method involves premaxillary bodily retraction followed by a
      gingivo-periosteoplasty. In both series of cases the palatal cleft (hard and
      soft) is closed for patients aged 18 to 30 months using a modified von Langenbeck
      procedure. A secondary alveolar bone graft is only performed in the
      conservatively treated series for patients aged 7 to 9 years. Although the
      premaxilla in 2 of 29 conservatively treated cases were retruded and in anterior
      crossbite by 10 to 12 years of age, all M-L cases were retruded by 9 years of age
      requiring maxillary protraction. In the M-L cases 90% showed bony bridging of the
      alveolar cleft with frequent loss of the lateral incisor space; surgical closure
      of the nasal floor is facilitated, and early aesthetic improvement is followed by
      midfacial retrusion.

PMID- 9161287
TI  - The relationship between timing of cleft palate surgery and speech outcome: what
      have we learned, and where do we stand in the 1990s?
AB  - The optimum age for surgical closure of cleft palate remains an unresolved
      question, despite the fact that many clinicians have studied the issue since the
      1930s. This article reviews the debate as it has taken shape over the last
      several decades, with a prospective view toward how standards of practice may
      evolve in the foreseeable future.

PMID- 9161288
TI  - Bone grafting for the alveolar cleft defect.
AB  - Seventy-five percent of all cleft lip and palate patients have osseous defects of
      the alveolus. Bone grafting of this defect normalizes facial and dental function.
      Failure to reconstruct the osseous deformity may result in oronasal fistula,
      fluid reflux, speech pathology, anteroposterior deficiency of the maxilla,
      transverse deficiency of the maxilla, lack of bone support for the incisors and
      cuspids, dental crowding, and facial asymmetry. Bone grafting unifies the maxilla
      and is best done after the majority of facial growth is complete and the
      secondary dentition is erupting. This is known as secondary bone grafting and
      yields the best results. The dentofacial deformity of cleft lip and palate is
      best managed by coordination of dental development, surgery and orthodontics.

PMID- 9161289
TI  - Orthodontic treatment for the cleft palate patient.
AB  - This article is an overview of the treatment possibilities and the role of the
      orthodontist in the management of patients with cleft palate. Orthodontic
      intervention and treatment may be indicated soon after birth (infant
      orthopedics), in the deciduous, mixed, and permanent dentitions and also in the
      adult patient. This article focuses primarily on decision-making and procedural
      steps performed by the orthodontist during the permanent dentition stage. The
      need for coordinated interaction with other team members is emphasized.

PMID- 9161290
TI  - Orthognathic surgery for the cleft lip and palate patient.
AB  - A thoughtful staged reconstruction for the cleft lip and palate patient is the
      preferred approach. The primary lip and palate repair performed during infancy
      and early childhood provides the foundation for normal speech, occlusion, facial
      appearance, and self-esteem. A long-term negative effect of these early surgical
      interventions is a significant incidence of maxillary growth restriction that
      produces secondary deformities of the jaws and dentition. This article reviews
      the variations in presentation, surgical and orthodontic techniques, and the
      results that we have achieved in patients born with a cleft who underwent primary
      repair in childhood, had a jaw deformity and malocclusion in adolescence, and
      underwent orthognathic surgery combined with orthodontic treatment for facial
      reconstruction and dental rehabilitation.

PMID- 9161291
TI  - Prosthetic rehabilitation of the cleft palate patient.
AB  - This article is a brief overview of prosthodontic and restorative methods used in
      the treatment of unilateral and bilateral cleft palate patients. Some past,
      present, and future methods of rehabilitation are discussed.

PMID- 9161292
TI  - Velopharyngeal impairment in the orthodontic population.
AB  - This article provides information concerning cleft palate teams and questions one
      might consider in identifying the best referral for patients manifesting
      velopharyngeal impairment. A discussion of the impact of velopharyngeal
      impairment on speech performance is followed by presentation of a variety of
      simple evaluative tasks that can assist the clinician in identifying patients who
      would benefit from referral to a cleft palate team. Finally, information is
      presented concerning the potential speech sequelae of maxillary advancement
      surgery.

PMID- 9161293
TI  - The Tweed philosophy: the Tweed years.
AB  - Charles H. Tweed revolutionized clinical orthodontics. His inquisitive scientific
      mind coupled with his outstanding clinical ability and his unselfish work ethic
      are legendary. He gave the orthodontic specialist diagnostic and mechanical
      treatment concepts that have stood the tests of both time and intense scrutiny.

PMID- 9161294
TI  - The Tweed-Merrifield philosophy.
AB  - Charles Tweed's concepts have been simplified, enhanced, and expanded by Levern
      Merrifield. Merrifield's ideas have augmented Tweed's to give orthodontics the
      Tweed-Merrifield philosophy. Adherence to the philosophy allows the orthodontic
      specialist to define objectives for the face, the skeletal pattern, and the
      teeth, and to diagnose and treat a malocclusion to efficiently reach these
      predetermined objectives.

PMID- 9161295
TI  - Differential diagnosis.
AB  - Differential diagnosis enables the orthodontic clinician to completely analyze
      and study a malocclusion. The differential diagnosis protocol of analyzing the
      face, the skeletal pattern, and the teeth enables the clinician to ascertain the
      area with the greatest disharmony, prioritize the attainable objectives, and
      arrive at a diagnosis and ultimately a treatment plan that will allow him or her
      to treat the greatest number of attainable objectives. Any differential
      diagnostic system must be used with an understanding of the concept that there
      are anterior, posterior, lateral, and vertical limits of the dentition. These
      boundaries are determined by bone and muscular limitations.

PMID- 9161296
TI  - Tweed-Merrifield sequential directional force treatment.
AB  - There are essentially five concepts which comprise the modern Tweed-Merrifield
      Sequential Directional Force treatment philosophy. These concepts are: (1)
      sequential appliance application, (2) sequential and/or individual tooth
      movement, (3) sequential mandibular anchorage preparation, (4) directional forces
      which control the vertical dimension to enhance mandibular response, and (5)
      proper timing of treatment. Tweed-Merrifield Sequential Edgewise Directional
      Force Treatment can be organized into four steps: denture preparation, denture
      correction, denture completion, and denture recovery. During each of these steps,
      there are certain treatment objectives that must be attained. This article
      outlines the modern Tweed-Merrifield treatment concept.

PMID- 9161297
TI  - Tweed-Merrifield sequential directional force nonpremolar extraction treatment: a
      case report.
AB  - The treatment of a Class II, Division 1 malocclusion without the extraction of
      premolars is, in many situations, the best solution for the patient. Nonpremolar
      extraction diagnosis followed by mechanotherapy with a nontorqued, nonangulated
      .022 edgewise appliance and the "Twelve-Two" System of Sequential Directional
      Force application is described.

PMID- 9161298
TI  - Correction of an angle Class II, division 1 malocclusion with the mesial movement
      of the mandibular molars: a case report.
AB  - Because of the wide variation found in Class II malocclusions, many different
      diagnostic decisions must be made. Treatment mechanics must, of necessity,
      differ. This case report describes the treatment of a Class II malocclusion
      which, for correction, required the extraction of maxillary first premolars and
      mandibular second premolars.

PMID- 9161299
TI  - Correction of a severe Class III malocclusion that required orthognathic surgery:
      a case report.
AB  - The horizontal and vertical considerations that must be taken into account during
      the diagnosis and subsequent treatment of the dentally and skeletally compromised
      patient are discussed. The treatment planning and treatment of a difficult
      malocclusion that required comprehensive orthodontics with surgical intervention
      are presented.

PMID- 9161300
TI  - WHO reform and global health.

PMID- 9161301
TI  - Pulmonary rehabilitation.

PMID- 9161302
TI  - Acupuncture: safety first.

PMID- 9161303
TI  - Gestational trophoblastic disease.

PMID- 9161304
TI  - Ice cream headache.

PMID- 9161305
TI  - Specialists criticise treatment for heroin addiction.

PMID- 9161306
TI  - MOD settles over Down's syndrome child.

PMID- 9161307
TI  - Older people take too many drugs.

PMID- 9161308
TI  - Effectiveness of antismoking telephone helpline: follow up survey.
AB  - OBJECTIVE: To evaluate the effectiveness of an antismoking campaign conducted by
      the Health Education Board for Scotland. DESIGN: Descriptive survey of adult
      callers to a telephone helpline (Smokeline) for stopping smoking; panel study of
      a random sample of adult callers; assessment of changes in prevalence of smoking
      in Scotland before and after introduction of the helpline. SETTING: Telephone
      helpline. SUBJECTS: Callers to Smokeline over the initial one year period.
      Detailed information was collected on a 10% sample (n = 8547). A cohort of adult
      smokers who called Smokeline (total n = 848) was followed up by telephone
      interview three weeks, six months, and one year after the initial call. MAIN
      OUTCOME MEASURES: Numbers of adult smokers calling helpline; changes in smoking
      behaviour, especially stopping smoking among cohort members; and changes in
      prevalence of smoking in the general population. RESULTS: An estimated 82782
      regular adult smokers made genuine contact with Smokeline over the year,
      representing about 5.9% of all adult smokers in Scotland. At one year 143 of the
      cohort of 848 callers (23.6%; 95% confidence interval 20.2% to 27.0%) reported
      that they had stopped smoking and 534 (88.0%; 85.4% to 90.6%) reported having
      made some change. About 19500 (16700 to 22350) adult smokers, equivalent to 1.4%
      (1.2% to 1.6%) of the mean adult smoking population, stopped smoking with direct
      help from Smokeling. During the second year of the campaign (1994) smoking
      prevalence among 25-65 year olds in Scotland was 6% (2.0% to 10.0%) lower than it
      had been before the start of the campaign. CONCLUSION: The Health Education Board
      for Scotland's antismoking campaign reached a high number of adult smokers, was
      associated with a highly acceptable quit rate among adults given direct help
      through Smokeline, and contributed considerably to an accelerated decline in
      smoking prevalence in Scotland.

PMID- 9161309
TI  - Mothers' birth weight and survival of their offspring: population based study.
AB  - OBJECTIVE: To test the hypothesis that a baby's survival is related to the
      mother's birth weight. DESIGN: Population based dataset for two generations.
      SETTING: Population registry in Norway. SUBJECTS: All birth records for women
      born in Norway since 1967 were linked to births during 1981-94, thereby forming
      105104 mother-offspring units. MAIN OUTCOME MEASURES: Perinatal mortality
      specific for weight for offspring in groups of maternal birth weight (with 500 g
      categories in both). RESULTS: A mother's birth weight was strongly associated
      with the weight of her baby. Maternal birth weight was associated with perinatal
      survival of her baby only for mothers with birth weights under 2000 g. These
      mothers were more likely to lose a baby in the perinatal period (odds ratio 2.3,
      95% confidence interval 1.4 to 3.7). Among mothers with a birth weight over 2000
      g there was no overall association between mother's weight and infant survival.
      There was, however, a strong interaction between mother's birth weight, infant
      birth weight, and infant survival. Mortality among small babies was much higher
      for those whose mothers had been large at birth. For example, babies weighing
      2500-2999 g had a threefold higher mortality if their mother's birth weight had
      been high (> or = 4000 g) than if the mother had been small (2500-2999 g).
      CONCLUSION: Mothers who weighed less than 2000 g at birth have a higher risk of
      losing their own babies. For mothers who weighed > or = 2000 g their birth weight
      provides a benchmark for judging the growth of their offspring. Babies who are
      small relative to their mother's birth weight are at increased risk of mortality.

PMID- 9161311
TI  - Concordance of phenprocoumon dosage in married couples.

PMID- 9161310
TI  - Cost effectiveness of day and inpatient psychiatric treatment: results of a
      randomised controlled trial.
AB  - OBJECTIVE: To compare direct and indirect costs of day and inpatient treatment of
      acute psychiatric illness. DESIGN: Randomised controlled trial with outcome and
      costs assessed over 12 months after the date of admission. SETTING: Teaching
      hospital in an inner city area. SUBJECTS: 179 patients with acute psychiatric
      illness referred for admission who were suitable for random allocation to day
      hospital or inpatient treatment. 77 (43%) patients had schizophrenia.
      INTERVENTIONS: Routine inpatient or day hospital treatment. MAIN OUTCOME
      MEASURES: Direct and indirect costs over 12 months, clinical symptoms, social
      functioning, and burden on relatives over the follow up period. RESULTS: Clinical
      and social outcomes were similar at 12 months, except that inpatients improved
      significantly faster than day patients and burden on relatives was significantly
      less in the day hospital group at one year. Median direct costs to the hospital
      were 1923 pounds (95% confidence interval 750 pounds to 3174 pounds) per patient
      less for day hospital treatment than inpatient treatment. Indirect costs were
      greater for day patients; when these were included, overall day hospital
      treatment was 2165 pounds cheaper than inpatient treatment (95% confidence
      interval of median difference 737 pounds to 3593 pounds). Including costs to
      informants when appropriate meant that day hospital treatment was 1994 pounds per
      patient cheaper (95% confidence interval 600 pounds to 3543 pounds). CONCLUSIONS:
      Day patient treatment is cheaper for the 30-40% of potential admissions that can
      be treated in this way. Carers of day hospital patients may bear additional
      costs. Carers of all patients with acute psychiatric illness are often themselves
      severely distressed at the time of admission, but day hospital treatment leads to
      less burden on carers in the long term.

PMID- 9161312
TI  - Acute angle closure glaucoma associated with paroxetine.

PMID- 9161313
TI  - Paroxetine and hepatotoxicity.

PMID- 9161314
TI  - Women's understanding of abnormal cervical smear test results: a qualitative
      interview study.
AB  - OBJECTIVE: To describe how women interpret their experiences of diagnosis and
      treatment of a cervical abnormality and how healthcare services for such women
      can be improved. DESIGN: Qualitative study using detailed individual interviews.
      SETTING: Australian gynaecology clinics. SUBJECTS: 29 Women who had a cervical
      cytological abnormality and who attended a gynaecologist. MAIN OUTCOME MEASURES:
      Women's views on their diagnosis and their information needs. RESULTS: Most women
      wanted to participate in decisions about their care but found it difficult to get
      the information they required from doctors because they were confused by what
      their doctors told them and felt unable to ask questions in the consultation.
      Medical terms such as wart virus and precancer were difficult to understand. Not
      being able to see their cervix also made it hard for women to understand what
      their abnormality meant and what treatment entailed. Most women tried to make
      sense of their abnormality in the context of their everyday lives. For some women
      their gynaecological care was not consistent with the way they understood their
      abnormality. CONCLUSIONS: The inherent power structure of medical practice
      combined with time pressures often make it difficult for doctors to give the
      detailed information and reassurance patients need when a diagnosis is
      distressing or when investigation and treatment are strange and upsetting.

PMID- 9161315
TI  - Seasonal allergic rhinitis.

PMID- 9161316
TI  - ABC of clinical haematology. The future of haematology, molecular biology, and
      gene therapy.

PMID- 9161317
TI  - Should egg donors be paid?

PMID- 9161318
TI  - The New World order and international health.

PMID- 9161319
TI  - Health care systems for the 21st century. Seventh Consultative Committee on
      Primary Health Care Systems for the 21st Century.

PMID- 9161320
TI  - The World Health Organisation needs to reconsider its definition of health.

PMID- 9161321
TI  - Do neuroleptic drugs hasten cognitive decline in dementia? Carriers of
      apolipoprotein E epsilon 4 allele seem particularly susceptible to their effects.

PMID- 9161322
TI  - Do neuroleptic drugs hasten cognitive decline in dementia? Trials must determine
      which neuroleptics are best in dementia.

PMID- 9161323
TI  - Do neuroleptic drugs hasten cognitive decline in dementia? Authors have not
      proved their argument.

PMID- 9161324
TI  - Intake of micronutrients in Britain's poorest fifth has declined.

PMID- 9161325
TI  - More women drink at hazardous levels in England than Italy.

PMID- 9161326
TI  - Prophylaxis should be considered even for trivial animal bites.

PMID- 9161327
TI  - Giving children adults' rights runs risk of making them adults before their time.

PMID- 9161328
TI  - Hypoplastic left heart syndrome. More families now have a choice.

PMID- 9161329
TI  - Hypoplastic left heart syndrome. Willingness to initiate treatment is crucial.

PMID- 9161330
TI  - Hypoplastic left heart syndrome. Quality of life is also important.

PMID- 9161331
TI  - National system for monitoring all drug use in pregnancy already exists.

PMID- 9161332
TI  - Hormone replacement therapy. Damage is done by pressure groups that distort the
      evidence.

PMID- 9161333
TI  - Hormone replacement therapy. Be cautious about using HRT for women without
      symptoms of oestrogen deficiency.

PMID- 9161334
TI  - Studies exploring health in relation to intrauterine life should look at birth
      order.

PMID- 9161335
TI  - Dictating clinic letters in front of the patient. Letting patients see copy of
      consultant's letter is being studied in trial.

PMID- 9161336
TI  - Dictating clinic letters in front of the patient. Further research should be
      qualitative.

PMID- 9161337
TI  - Dictating clinic letters in front of the patient. Effect of sending clients a
      personalised summary letter is being studied.

PMID- 9161338
TI  - Increasing doctors' confidence would solve low uptake of prehospital
      thrombolysis.

PMID- 9161339
TI  - Rate of hysterectomy is lower among female doctors and lawyers' wives.

PMID- 9161340
TI  - Health workers need information from countries with better health indicators than
      Britain and the US.

PMID- 9161341
TI  - Sentiweb remains efficient tool for nationwide surveillance of disease.

PMID- 9161344
TI  - A mandate for physician activism in the war against tobacco.

PMID- 9161345
TI  - The decision to seek care. Factors associated with the propensity to seek care in
      a community-based cohort of men.
AB  - OBJECTIVE: To investigate factors associated with a high propensity to seek care.
      DESIGN: Cross-sectional baseline component of a prospective cohort study.
      SETTING: Olmsted County, Minnesota. SUBJECTS: A randomly selected, community
      based cohort of 2115 men aged 40 to 79 years on January 1, 1990. MEASUREMENTS:
      Participants completed a questionnaire that elicited information about the
      propensity to seek care by means of 7 hypothetical scenarios about physical
      illness. Also queried was the self-reported outpatient physician utilization in
      the previous year and sociodemographic factors. RESULTS: There was a significant
      association between propensity to seek care and physician utilization. Men with a
      high propensity to seek care were more likely to have had 4 or more physician
      visits (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.3-2.3). Bivariate
      analysis suggested significant associations between a propensity to seek care for
      physical reasons and retirement (OR, 2.0; 95% CI, 1.1-2.6), age of 65 years or
      more (OR, 1.9; 95% CI, 1.5-2.4), incomplete high school education (OR, 1.6; 95%
      CI, 1.1-2.2), and an annual income of less than $25,000 (OR, 1.4; 95% CI, 1.1
      1.9). Multivariable logistic regression analysis demonstrated that retired men
      were more likely to have a high propensity to seek care (OR, 1.7; 95% CI, 1.2
      2.4), with the other variables no longer-being significant. CONCLUSIONS: Our
      findings suggest an association between propensity to seek care and physician
      utilization and retirement. In view of the increasing numbers of aged persons in
      the United States, this relatively higher propensity to seek health care among
      retired men may have a greater impact on the cost of health care for the aged
      than is fully appreciated.

PMID- 9161346
TI  - Periodic health examinations and the provision of cancer prevention services.
AB  - OBJECTIVES: To learn about cancer prevention services in primary care practices
      and to understand physician factors that affect the provision of these services.
      DESIGN: Survey of physicians and their patients in 1992. SETTING: Cooperating
      physicians (n = 72) of a random selection of community general internist and
      family physician practices in New Hampshire and Vermont. PATIENTS: Patients (n =
      2775) of the study physicians for at least 1 year, aged 42 years or older, with
      no life-threatening threatening illness, who recently visited the physician. MAIN
      OUTCOME MEASURES: Proportion of sample patients per practice provided age- and
      sex-appropriate cancer prevention services in the previous year. RESULTS: In this
      primary care population, a high proportion of patients received appropriate
      services in 1992. A periodic health examination within the past year was an
      important predictor for the receipt of many cancer prevention services. Female
      physicians provided more periodic health examinations than male physicians;
      internists provided more than family physicians. CONCLUSIONS: The strongest
      determinant of receiving preventive services is having a periodic health
      examination. If clinicians and policymakers decrease emphasis on the periodic
      health examination as a major opportunity to provide indicated preventive
      services, they should ensure that a satisfactory alternative strategy is in
      place.

PMID- 9161348
TI  - Competing priorities and comorbidities. So much to do and so little time.

PMID- 9161347
TI  - Treatment typically provided for comorbid anxiety disorders.
AB  - OBJECTIVE: To study whether the extent and type of treatment for comorbid anxiety
      disorders varies for patients with depression, hypertension, diabetes, and heart
      disease treated by general medical clinicians. METHODS: Data are from 2189
      general medical patients with and without comorbid anxiety disorders in the
      Medical Outcomes Study. Treatment data were based on clinician reports of
      counseling provided during a visit and patient reports of recent medication use.
      RESULTS: Patients with comorbid anxiety disorders were more likely to receive
      treatments for anxiety disorders than those without anxiety disorders. Among
      those with anxiety disorders, the use of psychosocial counseling and psychotropic
      medication was greater for patients with depression than for patients without
      depression who had chronic medical conditions. Minor tranquilizers were used more
      commonly than antidepressants, regardless of the type of comorbid condition.
      Among patients with anxiety disorders, those visiting medical subspecialists were
      more likely to use minor tranquilizers than those visiting family practitioners
      or internists. Patients of family physicians with chronic medical conditions (but
      not with depression) were less likely than similar patients of internists to use
      minor tranquilizers whether or not anxiety disorders were present. CONCLUSIONS:
      Anxiety disorders co-occurring with another disease (medical illness or
      depression) increases the likelihood of counseling and the use of psychotropic
      medication in the general medical sector. Patients with a chronic medical illness
      with or without comorbid anxiety disorders visiting family physicians are less
      likely to use minor tranquilizers than those visiting subspecialists or
      internists.

PMID- 9161349
TI  - Differential diagnosis of palpitations. Preliminary development of a screening
      instrument.
AB  - OBJECTIVE: To develop a self-report screening instrument to assist in the
      differential diagnosis of medical outpatients complaining of palpitations.
      DESIGN: Patients completed self-report questionnaires assessing somatization,
      cardiac symptoms, and hypochondriacal concerns about health. Principal components
      analysis was performed to identify a subset of questions that could be used to
      distinguish patients with palpitations who have panic disorder from those with
      palpitations who do not have panic disorder. PATIENTS: Sixty-seven medical
      outpatients referred for Holter monitoring because of a complaint of
      palpitations. MAIN OUTCOME MEASURES: Patients with palpitations were classified
      into 2 groups, those with and those without current panic disorder (established
      with a structured, diagnostic interview). The sensitivity, specificity, and
      posttest probability of the screening instrument were determined. RESULTS: A
      reliable, stable, 10-item instrument was derived. It seems to tap diffuse, vague,
      or generalized somatic complaints and worry about physical illness. With the use
      of a criterion cutoff score of 21, this instrument had a sensitivity of 0.81, a
      specificity of 0.80, and a post-test probability of.57 in detecting current panic
      disorder in patients with palpitations. CONCLUSIONS: A psychometrically sound and
      brief self-report instrument was developed to assist in the differential
      diagnosis of palpitations. It can be used to identify patients whose symptoms are
      more likely to result from panic disorder and in whom ambulatory monitoring might
      be deferred.

PMID- 9161350
TI  - Modifiable high-risk behaviors for cardiovascular disease among family physicians
      in the United States. A national Survey.
AB  - OBJECTIVES: To study the prevalence of modifiable high-risk behaviors that
      contribute to mortality and morbidity from cardiovascular disease among family
      physicians in the United States, to examine whether these prevalence rates would
      differ across geographic regions of the United States, and to determine whether a
      family history of coronary artery disease differentiated physicians who engage in
      these high-risk behaviors from those who do not. DESIGN: A mailed self-report
      survey. SETTING: Family physician members of the American Board of Family
      Practice. PARTICIPANTS: The survey was mailed to 1500 randomly selected members
      of the American Board of Family Practice. RESULTS: The response was 62%. The
      results showed that 97% of the physicians were nonsmokers, 54% engaged in
      exercise regularly, 36% considered themselves overweight, and 91% knew their
      lipid profile. Of the respondents, 63% reported having a family physician, 78%
      reported visiting their physician as needed, and 41% reported having had a
      physician visit in the past year. Forty-one percent of the physicians reported
      having a family history of coronary artery disease. There were no notable
      differences regarding the prevalence of these behaviors across the 5 geographic
      areas or between respondents with a family history of coronary artery disease and
      those without such a history. CONCLUSION: Our results suggest that the
      respondents as a group engage in health practices that help to prevent
      cardiovascular disease. However, the frequency of exercise among these physicians
      is below the recommended level, and efforts should be made in promoting exercise
      among this population.

PMID- 9161351
TI  - Values, stress, and coping among practicing family physicians.
AB  - OBJECTIVE: To determine the types of values, sources of stress, and methods of
      coping in a sample of community-based practicing family physicians who were
      determined as healthy and satisfied with their careers. DESIGN: Qualitative
      study, combining an interview guide approach with a standardized open-ended
      interview. SETTING: Offices of practicing physicians in Ohio. PARTICIPANTS: A
      purposeful sample of 10 central Ohio family physicians, ranging in age from their
      mid-30s to mid-60s; 8 were married; 2 were African American; 3 practiced in a
      rural environment; 3 worked in a solo practice, 5 in a partnership, and 2 in a
      group practice. The sample was identified by a knowledgeable informant, using a
      criterion of success in coping with occupational stress and satisfaction with the
      practice of medicine. MAIN OUTCOME MEASURE: Patterns and themes common to the
      interviews. RESULTS: Primary values presented by the sample included caring,
      diversity, control, family, and spirituality. Sources of stress involved
      overload, the nature of today's medical environment, and demanding patients.
      Coping strategies consisted of problem solving, developing a positive
      perspective, stress monitoring, support, and "time for self." Stress was often
      produced when a conflict existed between the person and the work environment.
      Stress was also created when the manifestation of values was unhealthy and
      unbalanced. CONCLUSIONS: Research participants described various learned
      strategies that enabled them to cope more effectively with stress. These were
      often developed after personal struggle with work or family. Results suggested
      that assessing the developmental processes in physician stress and coping is
      important.

PMID- 9161352
TI  - Efficacy of diclofenac in lateral epicondylitis of the elbow also treated with
      immobilization. The University of Montreal Orthopaedic Research Group.
AB  - OBJECTIVE: To evaluate the efficacy of an oral nonsteroidal anti-inflammatory
      drug in the treatment of lateral epicondylitis. DESIGN: Multicenter double-blind
      randomized controlled trial in which the following hypothesis was tested: whether
      diclofenac sodium provided a 20% or greater improvement over rest and cast
      immobilization in the response rate to treatment of lateral epicondylitis beyond
      and over rest in an experimental group compared with a control group after 4
      weeks of treatment. SETTING: Recruitment from urban general practices and
      referrals to 4 university hospitals. SUBJECTS AND METHODS: During a 1-year
      period, 206 subjects aged 18 to 60 years with lateral epicondylitis were
      recruited from the clientele treated by family physicians. Thirty subjects
      refused to participate and 47 presented with exclusion criteria, leaving 129
      subjects who entered the study. One subject withdrew after 21 days.
      INTERVENTIONS: The experimental group was treated with a daily dose of diclofenac
      sodium (150 mg) for 28 days, while the control group received a placebo during
      the same period. In addition, both groups were immobilized in a cast for 14 days
      and were told not to perform repetitive movements of the involved limb for 21
      days. MAIN OUTCOME MEASURES: Measuring instruments consisted of grip strength
      measurements with a squeeze dynamometer, a visual analog pain scale, a visual
      analog function scale, and an 8-item pain-free function index. RESULTS: A
      statistically and clinically significant reduction of pain was associated with
      treatment with diclofenac, but no clinically significant difference in grip
      strength or functional improvement could be detected between the 2 groups.
      Secondary effects (diarrhea and abdominal pain) were significantly more frequent
      in the diclofenac-treated group. CONCLUSION: Taking into account the limited
      improvement noted over rest and cast immobilization and the number of associated
      adverse events, it is difficult to recommend the use of diclofenac in the
      treatment of lateral epicondylitis at the dosage used in this study.

PMID- 9161353
TI  - Looking back in the medicine cabinet...

PMID- 9161354
TI  - The electronic house call. Consequences of telemedicine consultations for
      physicians, patients, and society.
AB  - Within the next 10 years, telemedicine technology is likely to become widely
      available in physicians' offices and patients' homes. Rather than describing the
      technology of telemedicine, we discuss the implications of its widespread use
      among physicians, patients, and society as a whole, focusing on that mainstay of
      communication between physician and patient, the "electronic house call." After
      exploring the new relationship that is likely to develop between patients and
      physicians as a consequence of the use of telemedicine, we discuss the broader
      economic, legal, and political consequences of the widespread use of this
      technology.

PMID- 9161356
TI  - Lessons for clinicians from physician-patient communication literature.
AB  - Research about the communication between physicians and patients contains
      information that can help clinicians be better diagnosticians and achieve greater
      compliance and can lead to improved patient health and satisfaction. We present
      research results that can be useful for the physician in daily clinical practice.

PMID- 9161355
TI  - The department without walls. Acceptability, cost, and utilization of interactive
      video technology.
AB  - As groups of physicians continue to provide more of their activities in sites
      remote from the central office, communication among providers and staff and the
      provision of common educational activities are important priorities. An analysis
      of a 12-month period of the use of full-motion interactive video technology to
      accomplish these goals in a decentralized academic department shows this method
      to be acceptable and cost-effective. Careful attention to room environment and
      staff support were found to be important. Practical recommendations are provided
      for those considering the use of this technology.

PMID- 9161357
TI  - Accessing the scientific literature. The reality of virtual scholarship.
AB  - The age-honored practice of plowing through the Index Medicus in a good medical
      library to meander through citations for treasured finds is an anachronism.
      Today, clinicians have the astonishing capacity to bring to bear existing
      knowledge almost effortlessly. Virtual scholarship makes available up-to-date
      medical citations and their abstracts. There can be access around the clock on
      any topic in the office, at the bedside, or from home. Computerized searches of
      the medical literature promote directed continuing education and may enhance
      clinical care of patients.

PMID- 9161358
TI  - Human immunodeficiency virus infection in patients older than 50 years. A survey
      of primary care physicians' beliefs, practices, and knowledge.
AB  - To assess primary care physicians' attitudes, knowledge, and practices with
      respect to the human immunodeficiency virus (HIV) in older patients, a
      prospective survey of a representative cohort of primary care physicians was
      conducted in Dallas County, Texas, a large metropolitan area. Three hundred
      thirty primary care physicians participated in the survey. Questions were asked
      regarding physician demographics, practice characteristics, and knowledge and
      practices with respect to HIV and the acquired immunodeficiency syndrome (AIDS)
      in patients older than 50 years. The responses of the following groups were
      compared: family practitioners vs internists, physicians younger than 40 years vs
      those aged 40 years and older, those who saw 5 or less vs more than 5 patients
      with HIV or AIDS per year, and those in private vs nonprivate practice. Most
      respondents (85.5%) reported having seen 10 or fewer patients with HIV or AIDS in
      the previous year. Most physicians (69.7%) reported that patients older than 50
      years rarely or never asked questions concerning HIV or AIDS. Most physicians
      rarely or never discussed HIV or AIDS with patients older than 50 years (60.8%)
      and rarely or never discussed risk factor reduction (67.5%). Physicians were more
      likely to rarely or never ask patients older than 50 years compared with those
      younger than 30 years about HIV risk factors (40.0% vs 6.8%, P < .001).
      Physicians incorrectly rank ordered the most prevalent risk factors in patients
      older than 50 years. The correct order is (1) male-male sex, (2) intravenous drug
      use, (3) blood transfusion, and (4) heterosexual sex. Physicians aged 40 years
      and older were more likely to correctly identify the most prevalent risk factor
      (P = .03). Family practitioners were more likely to rarely or never ask older
      patients about risk factors for HIV (54.9% vs 28.9%, P = .007). Primary care
      physicians have inadequate knowledge concerning HIV and AIDS risk factors in
      older patients and insufficiently discuss HIV and AIDS with older patients.
      Physicians should counsel patients of all ages about HIV and AIDS.

PMID- 9161359
TI  - Prescription errors. Legibility and drug name confusion.
AB  - Inadvertent drug substitution occurred in several instances in our practices due
      to the combination of the physician's illegible handwriting on prescriptions and
      the pharmacist's misinterpretation of subtle clues, which might have prevented
      the errors. The literature on the legibility of physician handwriting is
      reviewed. Our specific recommendations include using preprinted prescription
      pads, training staff assistants who write prescriptions, printing complete
      directions on each prescription, and aggressively educating each patient about
      the name and purpose of all drugs being prescribed. Patients are encouraged to
      bring their medications to each office visit to identify potential errors.

PMID- 9161360
TI  - Nocturnal polyuria and antidiuretic hormone levels in spinal cord injury.
AB  - OBJECTIVE: To establish baseline ADH levels in spinal cord injury patients and to
      evaluate whether spinal cord patients have attenuation of diurnal variation of
      ADH similar to children with enuresis and elderly with nocturnal polyuria.
      DESIGN: Twenty-seven healthy quadriplegic patients, ASIA impairment scale A, were
      evaluated for serum ADH levels at night and during the day. MAIN OUTCOME
      MEASURES: Evaluation of whether bladder overdistention caused by attenuation of
      diurnal variation of ADH is responsible for the episodes of autonomic dysreflexia
      and recurrent urinary tract infections in spinal cord injury patients who are on
      intermittent catheterization for bladder management. RESULTS: A lack of diurnal
      variation of ADH in the subject population. CONCLUSIONS: A trial of
      desaminocystein-D-arginine vasopressin (DDAVP) should be considered for patients
      with established attenuation of the diurnal variation ADH.

PMID- 9161361
TI  - A simple method for administering vancomycin in the spinal cord injured
      population.
AB  - OBJECTIVE: To examine the applicability in patients with spinal cord injury (SCI)
      of a modified version of the commonly used Lake and Peterson dosing regimen for
      vancomycin. DESIGN: Nonrandomized, prospective clinical trial with a historical
      control. SETTING: Spinal cord injury unit at a Veterans Affairs Medical Center.
      PATIENTS: Hospitalized patients with a history of SCI at least 6 months earlier
      and an estimated creatinine clearance of > or = 15 mL/min who required vancomycin
      therapy. The experimental group consisted of 15 evaluable patients, 8 with
      tetraplegia and 7 with paraplegia. INTERVENTION: Vancomycin regimens were
      initiated using a modified version of the guidelines of Lake and Peterson. MAIN
      OUTCOME MEASURE: After 4 to 8 doses, peak vancomycin concentrations in serum were
      obtained 15 minutes after a 1-hour infusion, and trough concentrations were drawn
      within 30 minutes of the next scheduled dose. RESULTS: Only 3 of 15 (20%)
      patients in the experimental group required a single adjustment in the dosing
      interval to achieve the targeted serum vancomycin concentrations. The proportion
      of patients who required dosing modification was significantly lower in the
      experimental group than in a group of 16 SCI control patients who received
      vancomycin according to the dosing recommendations in the drug insert (20% vs
      75%, respectively; p = .002). CONCLUSION: These results support the need for
      tailored vancomycin dosing in the SCI population and the efficacy of this simple
      method of administering vancomycin in achieving desirable concentrations of
      vancomycin in the serum of SCI patients.

PMID- 9161362
TI  - Balance and vertical impact in sports: role of shoe sole materials.
AB  - OBJECTIVE: Athletic shoes and mats are support surface interfaces composed of
      relatively soft compressible materials designed to protect against injuries
      occurring in sports through force of vertical impact. Impact remains high with
      their use because humans land harder with them. We hypothesize that this hard
      landing strategy is an attempt by the user to improve stability, by compressing
      the material to a less destabilizing thinner-stiff variety. We tested this
      hypothesis by comparing impact and balance on materials consisting of ethyl-vinyl
      acetate (EVA) foams of varying stiffness, identical to that found in soles of
      athletic footwear. DESIGN: Randomized-order, crossover trial, controlled
      comparison, blinded. SETTING: Volunteers were selected from the general
      community. PARTICIPANTS: A random sample of 12 healthy men from the general
      population (mean age 30 years, SD +/- 6). Additional selection criteria were
      absence of disabilities influencing ability to walk, run, and balance, and no
      history of frequent falls. METHODS: Impact testing and stability measures were
      performed on the same test day. Ground reaction forces were measured for ten
      barefoot footfalls. The protocol required stepping forward from perch to surface
      4.5 cm below. Stability testing was performed with one-legged standing consisting
      of placing left foot on top of right for 30 sec, barefoot, eyes open, and gaze
      straight, with arms to side. Subjects confronted four surface conditions
      presented in random order: a bare rigid platform, and the platform covered with
      one of three 2.5-cm-thick materials. RESULTS: Steady state vertical impact was a
      negative function of interface stiffness, with the softest interface producing
      the greatest vertical impact, and the stiffest interface the least vertical
      impact. Vertical impact and stability measures were also negatively related, with
      the strongest correlation obtained with the softest interface (r = -.87, p <
      .001). No relation between these variables was obtained for the rigid surface.
      CONCLUSION: Balance and vertical impact are closely related. This supports the
      hypothesis that landing hard on soft surfaces is an attempt to transform the
      interface into a form associated with improved stability. According to these
      findings, currently available sports shoes and mats are too soft and thick, and
      should be redesigned to protect the persons using them.

PMID- 9161363
TI  - Relapsing significant bacteriuria: effect on urinary tract infection in patients
      with spinal cord injury.
AB  - OBJECTIVE: To evaluate whether there is a relation between relapsing significant
      asymptomatic bacteriuria (ASB) and symptomatic urinary tract infection (UTI), and
      to determine the frequency rate of UTI in patients with spinal cord injury (SCI)
      using indwelling catheters (IC). DESIGN: Cohort study. Patients were followed up
      for 24 to 270 days (mean, 66.3 +/- 42.2). SETTING: A department of physical
      therapy and rehabilitation in a research hospital of a university referral
      center. PATIENTS: Fifty patients with SCI using IC. Patients with severe
      concurrent illness, known vesicouretheral reflux, urinary calculi, and severely
      disturbed renal function were excluded. MAIN OUTCOME MEASURE: Symptomatic UTI,
      relapsing ASB, and recurrent significant ASB. RESULTS: There was significant
      difference between relapsing ASB and recurrent ASB with regard to occurring
      symptomatic UTI (chi 2, 4.92; p < .03). Symptomatic UTI was observed at a rate of
      9.35, relapsing ASB 35.59, and recurrent ASB 55.80 per 1,000 patient-days.
      CONCLUSION: Relapsing ASB is an important factor in the development of
      symptomatic UTI.

PMID- 9161364
TI  - Gait electromyography in children with myelomeningocele at the sacral level.
AB  - OBJECTIVE: Patients with sacral level myelomeningocele can be expected to
      maintain a high level of ambulatory status long into adulthood. Gait
      deterioration and knee pain reported in this population may be attributed to
      compensatory movements and increased recruitment of less affected muscle groups
      to achieve this desired level of ambulation. The objective of this study was to
      analyze the effect of the solid ankle-foot-orthoses (AFOs) on the muscular
      activity of selected muscles during walking. DESIGN: Cohort/outcome. SETTING:
      Laboratory. PATIENTS: Twenty four patients with sacral level myelomeningocele
      between 4 to 17 years of age. INTERVENTION: Electromyographic activity of
      selected muscle groups were studied during barefoot walking and walking with
      solid AFOs at a self-selected walking velocity. MAIN OUTCOME MEASURES: Timing of
      electromyographic activity and sagittal plane knee kinematics. Comparison to
      normal electromyographic patterns and changes between barefoot and AFO walking
      conditions. RESULTS: With the AFOs there was significantly less prolonged stance
      phase quadriceps activity compared with barefoot walking, although greater than
      normal activity persisted. There was no change between conditions for the other
      monitored muscle groups. All muscles elicited greater duration of activity over
      the course of the gait cycle. CONCLUSIONS: Our results show that solid AFOs
      improve the prolonged knee extensor activity evident for barefoot walking. This
      is clinically relevant to the gait deterioration and knee pain sometimes seen in
      this patient population. We espouse early and persistent orthotic intervention to
      reduce compensatory muscular overactivity and maintain gait quality.

PMID- 9161365
TI  - Lower extremity residual limb slippage within the prosthesis.
AB  - OBJECTIVE: The ability to measure skin surface slippage relative to the internal
      wall of a lower extremity prosthesis under various loading conditions is
      important for evaluation of socket fit and function, and creation of finite
      element models. Skin surface three-dimensional (3D) shape measurements with
      tracking of fiducial displacements in situ under axial loading of the prosthesis
      have not previously been reported. Analysis of slippage within the prosthesis has
      been performed using a new experimental measurement method based on spiral x-ray
      computed tomography (SXCT) imaging. DESIGN: Small lead markers were placed on the
      residuum of an adult with a below-knee amputation, and SXCT scans were obtained
      with the prosthesis in situ under two static axial loading conditions (44.5N and
      178N). The 3D scan data were used to assess slippage with three methods: gross
      displacement of the tibia and distal end of the residuum; relative displacement
      of markers; and distance measurements between markers. RESULTS: The markers
      affixed to the below-knee skin surface within the prosthesis were measured. The
      skin slipped from 2 to 6 mm relative to the internal prosthesis wall when an
      additional load of 133.5N was applied in the axial direction to the distal end of
      the prosthesis. The tibial remnant moved 10.0 mm distally relative to the
      prosthesis internal wall. CONCLUSION: This method provides a feasible means for
      measuring residuum skin slippage relative to the prosthesis and skin deformation
      relative to tibia within an in situ prosthesis under load.

PMID- 9161366
TI  - Flexion relaxation of the hamstring muscles during lumbar-pelvic rhythm.
AB  - OBJECTIVE: This study investigated the simultaneous activity of back muscles and
      hamstring muscles during sagittal forward body flexion and extension in healthy
      persons. The study was cross-sectional. DESIGN: A descriptive study of paraspinal
      and hamstring muscle activity in normal persons during lumbar-pelvic rhythm.
      SETTING: A university hospital. PARTICIPANTS: Forty healthy volunteers (21 men,
      19 women, ages 17 to 48 years), all without back pain or other pain syndromes.
      MAIN OUTCOME MEASURES: Surface electromyography (EMG) was used to follow
      activities in the back and the hamstring muscles. With movement sensors, real
      lumbar flexion was separated from simultaneous pelvic motion by monitoring the
      components of motion with a two-inclinometer method continuously from the initial
      upright posture into full flexion. All signals were sampled during real-time
      monitoring for off-line analyses. RESULTS: Back muscle activity ceased (ie,
      flexion relaxation [FR] occurred) at lumbar flexion with a mean of 79 degrees.
      Hamstring activity lasted longer and EMG activity ceased in the hamstrings when
      nearly full lumbar flexion (97%) was reached. After this point total flexion and
      pelvic flexion continued further, so that the last part of lumbar flexion and the
      last part of pelvic flexion happened without back muscle activity or hamstring
      bracing, respectively. CONCLUSIONS: FR of the back muscles during body flexion
      has been well established and its clinical significance in low back pain has been
      confirmed. In this study, it was shown for the first time that the hip extensors
      (ie, hamstring muscles) relax during forward flexion but with different timing.
      FR in hamstrings is not dependent on or coupled firmly with back muscle behavior
      in spinal disorders and the lumbar pelvic rhythm can be locally and only
      partially disturbed.

PMID- 9161367
TI  - Quantification of upper extremity function using kinematic analysis.
AB  - OBJECTIVE: To illustrate the applicability of motor control analytical techniques
      to the assessment of upper limb dysfunction in children with ataxia. DESIGN:
      Descriptive case series. SETTING: The study sample was selected from an
      outpatient pediatric rehabilitation clinic and testing was performed in a
      research laboratory. PARTICIPANTS: Four children with upper limb ataxia and seven
      healthy children were examined. All subjects were recruited on a volunteer basis.
      Criteria for inclusion (ataxic group) included: (1) age 6 to 15 yrs; (2)
      ambulatory with assistive devices. MAIN OUTCOME MEASURES: Quantitative measures
      of elbow kinematics (movement speed and duration) and spatio-temporal "portraits"
      of elbow movement during unilateral and bilateral forward reaching movements.
      RESULTS: Movements made by ataxic subjects were characterized by lower peak
      velocities, prolonged durations, and increased variability compared with normal
      subjects. In the one subject with unilateral ataxia, interlimb coordination was
      severely disrupted during the performance of coupled, bilateral arm movements. In
      addition to changes in specific kinematic values (eg, peak velocity), phase plane
      and angle-angle displacement curves revealed marked spatio-temporal variability
      throughout the movement, the magnitude of which was correlated with severity of
      ataxia. CONCLUSION: The application of the quantitative motor control methods
      described in this report can provide rehabilitation specialists with a simple yet
      sensitive means to evaluate treatment and progression of a wide variety of motor
      disorder conditions. These techniques are particularly well suited to pediatric
      populations as young as 6 years.

PMID- 9161368
TI  - Interlimb interaction and stabilization of contralateral leg in isokinetic knee
      evaluation.
AB  - OBJECTIVE: To determine if peak torque (PT) production during isokinetic knee
      testing is affected by the stabilization and movement patterns of the
      contralateral leg. DESIGN: Repeated measure design. INTERVENTION AND MAIN OUTCOME
      MEASURE: Thirty subjects participated in comparing the force outputs in relation
      to the movement pattern of both legs. Another group of 45 subjects volunteered to
      perform five maximal isokinetic extension-flexion contractions in each of three
      different knee testing conditions: (1) without stabilization of the contralateral
      leg; (2) with a bar in front of the ankle joint of the contralateral leg; (3)
      with the contralateral leg strapped just above the level of the malleoli and the
      muscles of that leg induced reciprocally to perform isometric contractions with
      respect to the testing leg. PT was used to compare the strength of three
      different conditions. RESULTS: Significantly greater PT was measured when the
      contralateral leg of the subject was fixed and induced to contract reciprocally.
      CONCLUSION: More rigorous standardization of isokinetic strength testing
      procedures is needed due to differences in PT production of knee muscles
      according to the stabilization and movement pattern of the contralateral leg.

PMID- 9161369
TI  - Concentric and eccentric isokinetic measurements in knee muscles during the
      menstrual cycle: a special reference to reciprocal moment ratios.
AB  - OBJECTIVE: To investigate the effects of menstrual cycle on the reliability of
      concentric (CON) and eccentric (ECC) isokinetic measurements and reciprocal
      moment ratios in knee muscles. DESIGN: Repeated measurements. SETTING: A
      university exercise physiology laboratory. PARTICIPANTS: Sixteen healthy
      sedentary women volunteers, aged 24 to 35 years, who had regular menstrual cycle
      (ranging from 24 to 32 days). METHODS: Subjects were tested at 60 degrees/sec (4
      repetitions) and 180 degrees/sec (20 repetitions) of angular velocities for CON
      and ECC tests at the menstrual (MP, days 1 to 3), follicular (FP, days 7 to 10),
      and luteal phases (LP, 19 to 21). Blood samples were analyzed for sex hormones at
      the FP and LP. RESULTS: ECC and CON peak torques and total works, and their
      reciprocal ratios in dominant knee muscles, were not significantly different
      among the phases by ANOVA. Intraclass correlation coefficients (ICCs) among the
      phases for peak torque and total work of knee extensors in both angular
      velocities were in the range of .68 to .91 and .45 to .84 for CON and ECC tests,
      respectively. However, it was in the range of .03 to .72 and .65 to .94 for CON
      and ECC tests of knee flexors, respectively. In addition, there were no
      significant correlations between sex hormones and tested variables. CONCLUSION:
      The results suggest that the phase of the menstrual cycle should not be taken
      into account in isokinetic measurements.

PMID- 9161370
TI  - Snapping scapula syndrome: three case reports and an analysis of the literature.
AB  - The snapping scapula syndrome is an infrequently described source of shoulder
      discomfort characterized by painful, audible, and/or palpable abnormal
      scapulothoracic motion. The syndrome may be caused by skeletal or soft-tissue
      abnormalities that interfere with articulation between the scapula and the rib
      cage. Often, no obvious source of the snapping can be identified with imaging
      studies. Three new cases with electrodiagnostic and imaging studies are
      presented. For the first time a critical analysis and review by diagnoses,
      gender, age, treatment, and outcome of 89 reported cases is presented. Accurate
      recognition of the syndrome may lead to prompt and long-term relief of symptoms
      by conservative or surgical treatment.

PMID- 9161371
TI  - Electrical stimulation prevents immobilization atrophy in skeletal muscle of
      rabbits.
AB  - OBJECTIVE: To investigate the effect of unilateral cast immobilization with and
      without surface electrical stimulation (ES) on the tibialis anterior (TA) muscle
      of rabbits. DESIGN: Prospective randomized trial. SETTING: University medical
      school. ANIMALS: 53 New Zealand White rabbits (aged 54 to 63 days, weight 1.73 to
      1.91 kg). METHODS AND INTERVENTION: Random assignment, for a 3-week period, to
      one of four groups: C group (control group), I group (immobilization group), S
      group (group of electrical stimulation which was stimulated isometrically at 50
      Hz, 30 minutes per day, 5 times a week), and IS group (immobilization group
      which, like the S-group, received electrical stimulation). OUTCOME MEASURES:
      Muscle wet wight, muscle fiber cross-sectional area, muscle fiber types, and
      muscle capillary supply. RESULTS: Muscle wet weight decreased significantly in
      the I group by 19% (p < or = .05), with a corresponding significant reduction in
      the total muscle fiber cross-sectional area of 26% (p < or = .05). No significant
      changes were observed in muscle wet weight and muscle fiber cross-sectional area
      in the S and IS groups. Interstitial fibrosis was observed in the I group and
      occasionally in the IS group. No significant changes in the total number of
      muscle fiber types I and II were found in all experimental groups. The capillary
      supply of the S and IS groups did not change significantly. However, capillary-to
      fiber ratio was significantly reduced by 20% with a simultaneously nonsignificant
      increase in capillary density (capillaries/mm2) of 11% (p > .05) in the I group.
      Furthermore, muscle fiber regeneration was observed predominantly in the I group.
      CONCLUSIONS: In this experimental model, ES effectively prevented immobilization
      induced muscle atrophy by minimizing reduction of muscle fiber cross-sectional
      area, interstitial fibrosis, and impaired blood supply.

PMID- 9161372
TI  - Diagnostic value of different neurophysiological methods in the assessment of
      lumbar nerve root lesions.
AB  - OBJECTIVE: To investigate the sensitivity of a combination of different
      neurophysiological testing methods in patients with lumbar nerve root lesions.
      DESIGN AND SETTING: A prospective study was carried out in an electrodiagnosis
      laboratory on 57 patients with clinically proven lumbar radiculopathies. PATIENTS
      AND INTERVENTIONS: On 9 patients with L4 nerve root lesions, 31 patients with L5
      nerve root lesions, and 17 patients with S1 nerve root lesions, extensive
      electromyography (EMG), nerve conduction studies, F-wave-deviations, and
      somatosensory evoked potentials (SEPs) were performed. RESULTS: In 93% of all
      patients, a pathological neurophysiological result was found. In L4 nerve root
      lesions, EMG was abnormal in 89%, dermatome SEPs were abnormal in 67%, and F-wave
      latencies were abnormal in 44%. In L5 nerve root lesions, a pathological result
      was found on EMG in 87%, in peroneus SEPs in 67%, and in F-wave latencies in 66%.
      In S1 nerve root lesions, the most sensitive results were from dermatome SEPs in
      64%, followed by EMG in 53% and F-wave latencies in 24%. Nerve conduction study
      results were always normal. CONCLUSION: There are segment-specific
      neurophysiological results. It is possible to enhance testing sensitivity by a
      combination of different neurophysiologic testing methods. On these grounds, we
      recommend a segment-specific neurophysiological "diagnosis scheme" to corroborate
      the clinical diagnosis in lumbar nerve root lesions.

PMID- 9161374
TI  - Botulinum toxin treatment of apraxia of eyelid opening in progressive
      supranuclear palsy: report of two cases.
AB  - We report two patients, with postural instability and dystonic parkinsonism whose
      adjunctive disabling feature was blindness due to an inability to reopen the eyes
      after voluntary closure of the eyelids, as in apraxia of lid opening (ALO).
      Supranuclear downgaze paresis permitted the diagnosis of progressive supranuclear
      palsy (PSP) in one case. Electromyographic studies showed a loss of normal
      reciprocal inhibition between the levator palpebrae and the pretarsal portion of
      the orbicularis oculi, with a cocontraction of these two antagonist muscles. The
      evoked blink reflex, tested with the paired shock technique, showed enhanced
      recovery of R2 response. Botulinum toxin A injections directed toward the
      junction of the preseptal and pretarsal parts of the palpebral orbicularis oculi
      muscle improved eyelid motility in both patients. Successive static and dynamic
      balance training and development of compensatory strategies for visual scanning
      deficits reduced gait imbalance, the number of falls, and the disability level as
      measured on the Northwestern University Disability Scale.

PMID- 9161373
TI  - Gabapentin for relief of upper motor neuron symptoms in multiple sclerosis.
AB  - OBJECTIVE: To examine the efficacy of gabapentin in the treatment of spasticity
      and painful muscle spasms in patients with multiple sclerosis. DESIGN: Double
      blind, placebo-controlled crossover study. SETTING: Free-standing, 93-bed,
      university-affiliated rehabilitation hospital. PARTICIPANTS: There were 15
      patients between the ages of 18 and 50 who had laboratory-supported definite
      multiple sclerosis with spasticity and leg cramps severe enough to interfere with
      daily activities, including sleep. INTERVENTION: The patients received the
      placebo or 400mg gabapentin orally three times a day for 48 hours with an 11-day
      washout period. If the patients were on currently accepted modes of therapy,
      including oral baclofen, their current medication was not changed. MAIN OUTCOME
      MEASURES: The outcome measures were Visual Faces Scale rating, Kurtzke Disability
      Scale, quantitative surface electromyography, Ashworth Scale, presence or absence
      of clonus in response to rapid ankle dorsiflexion and wrist extension, presence
      or absence of reflex withdrawal in response to nailbed pressure to the first
      finger, and assessment of Babinski response. RESULTS: Statistically significant
      improvements for the gabapentin treated patients were found in the Ashworth
      Scale, Visual Faces Scale, and Kurtzke Disability Scale. CONCLUSIONS: At a dose
      of 400mg orally three times a day, gabapentin may be of value in the treatment of
      the spasticity and painful muscle cramping experienced by patients with multiple
      sclerosis.

PMID- 9161375
TI  - Tethered thoracic cord resulting from spinal cord herniation.
AB  - Tethered cord syndrome (TCS) usually involves tethering of the lower cord at the
      conus medullaris from dural abnormalities, but may occur after spinal cord
      herniation. A tethered thoracic spinal cord is rare. We present an unusual case
      of a 30-year-old woman with a history of myelopathy presumed to be secondary to
      T6 cord compression resulting from T6-T8 arachnoid cyst. She continued to
      deteriorate after partial excision of the cyst. Repeat magnetic resonance imaging
      suggested recurrence of the presumed arachnoid cyst with cord compression and
      showed tethering at T6-T8. Surgical exploration revealed myelocele with cord
      herniation through the anterior thoracic dura. Pathologic diagnosis showed neural
      tissue with gliosis. After physical therapy treatments, the patient had increased
      lower extremity strength, ambulated with a cane, and regained some bladder
      control. Progressive myelopathy may represent tethering of the cord resulting
      from cord herniation. Early recognition of TCS, even in patients with minimal
      neurologic deficits, could prevent progressive disability.

PMID- 9161376
TI  - Gynecomastia following spinal cord disorder.
AB  - Gynecomastia, an excessive development of the mammary glands in men, is a known
      phenomenon among patients with spinal cord disorder, yet in the last 50 years it
      has not been fully described in relation to spinal cord disorder. Over a period
      of 2 years, six patients with spinal cord disorder (4 secondary to a traumatic
      injury, 1 to decompression sickness, and 1 to transverse myelitis) manifested
      gynecomastia. The onset of gynecomastia occurred between 1 to 6 months after
      injury. These patients are presented along with a review of the possible causes
      for gynecomastia and a suggested workup routine. A clinical examination for the
      presence of gynecomastia should be performed for every patient with spinal cord
      disorder and a thorough endocrinological workup should follow to rule out
      malignancy and reassure the anxious patient undergoing a disruption of his body
      image.

PMID- 9161377
TI  - Calf vein thrombosis in spinal cord injured patients: conservative management of
      two cases.
AB  - Several studies have suggested that if a calf vein thrombosis does not propagate
      above the knee when followed up with serial diagnostic studies, full
      anticoagulation may not be necessary. These studies have not included spinal cord
      injured patients. Two patients with spinal cord injury were diagnosed with acute
      calf vein thrombosis after admission to a spinal cord injury rehabilitation unit.
      Both patients refused intravenous heparinization. Serial duplex Doppler studies
      were performed on both patients to evaluate for propagation of thrombus. Neither
      patient developed propagation of thrombus, pulmonary embolus, or persistent
      thrombophlebitis. Full anticoagulation including intravenous heparinization is
      costly, subject to complications, and interferes with intensive rehabilitation
      therapies. Observation of calf vein thrombosis with appropriate serial follow-up
      studies may be a viable alternative to anticoagulation in spinal cord injured
      patients. Further studies need to be done with this unique patient population.

PMID- 9161378
TI  - Cerebral salt wasting syndrome in brain injury patients: a potential cause of
      hyponatremia.
AB  - Hyponatremia is a common neuromedical problem seen in survivors of central
      nervous system injury. The etiology of this hyponatremia is often diagnosed as
      syndrome of inappropriate diuretic hormone (SIADH). Fluid restriction is usually
      the first line of treatment. However, this can exacerbate vasospasm and produce
      resultant ischemia. Cerebral salt wasting is a syndrome of renal sodium loss that
      may occur commonly after central nervous system injury, yet remains unrecognized.
      Treatment of cerebral salt wasting consists of hydration and salt replacement.
      This article uses a case report to discuss the importance of recognition of this
      syndrome, and treatment concerns are reviewed.

PMID- 9161379
TI  - Kernohan-Woltman notch phenomenon: an unusual cause of ipsilateral motor deficit.
AB  - Posttraumatic ipsilateral motor deficits are rare and raise etiologic and
      prognostic concerns for the rehabilitation team. We present two cases with an
      unusual central neurologic cause of ipsilateral weakness. The first patient was
      assaulted, with a resultant severe traumatic brain injury. Initial computed
      tomography showed a large right subdural hematoma (SDH) with significant mass
      effect. Following a craniotomy for evacuation of the SDH, the patient was noted
      to have paradoxical right-sided (ipsilateral) motor deficits. Postoperative
      magnetic resonance imaging (MRI) showed compression of the contralateral (left)
      cerebral peduncle against the tentorium, thus resulting in ipsilateral (right
      sided) motor weakness (the Kernohan-Woltman notch phenomenon). Prior limited
      reports carried a grave prognosis for these patients. On discharge from inpatient
      rehabilitation, the patient was functioning at a Rancho Los Amigos Scale VI. The
      second patient was involved in a motor vehicle accident and was found to have a
      large left frontotemporal subdural hematoma with shift. A dense left hemiplegia
      was noted after hematoma evacuation. MRI also showed a right cerebral peduncle
      hypointensity. At discharge, the patient was rated a Rancho Los Amigos Scale VI.
      Physiatrists need to be aware of the causes of ipsilateral motor weakness as well
      as the limitations of prognostic data.

PMID- 9161380
TI  - Cerebral diaschisis following cerebellar hemorrhage.
AB  - In 1914, Von Monakow described diaschisis, the recovery of lost cortical function
      in regions positionally distant from, but linked by neuronal tracts to, the
      primary site of cortical damage. Cerebellar diaschisis after cortical insult is
      detailed in the literature; however, cortical diaschisis after cerebellar insult
      remains a rarely reported occurrence. We describe a 36-year-old woman with
      rupture of a right-sided cerebellar arteriovenous malformation who developed such
      expected cerebellar signs as ataxia, dysmetria, and nystagmus. Days later, the
      patient developed profound impulsivity, disinhibition, and psychomotor agitation.
      Single photon emission computed tomography (SPECT) showed decreased perfusion of
      the bilateral frontal and temporal lobes, consistent with regional loss of neural
      activity. Eventual clinical improvement corresponded with reperfusion of those
      regions, identified on follow-up SPECT. This case documents cortical diaschisis
      following cerebellar insult and shows that diaschisis must be considered in
      patients with cerebral injury manifesting cortical deficits remote from the site
      of primary pathology.

PMID- 9161381
TI  - Reversion to a previously learned foreign accent after stroke.
AB  - Foreign accent syndrome occurs rarely after stroke. Most patients with this
      syndrome develop an aphasia characterized by a new accent. This report presents a
      48-year-old man who sustained a left parietal hemorrhagic stroke resulting in
      right hemiparesis and the inability to speak. As spontaneous speech emerged
      several weeks later, he was noted to have a Broca's aphasia and a Dutch accent.
      Analysis of his speech demonstrated final consonant deletion, substitution of "d"
      for "th" sounds, vowel distortions, additional "uh" syllables added at the end of
      words, and errors in voicing. This speech pattern has persisted for more than 5
      years after the stroke. Elicitation of additional history found that the patient
      was born in Holland and lived there until the age of 5 years, when he moved to
      the United States with his family. Before his stroke, he had no foreign accent.
      This report illustrates the importance of considering foreign accent syndrome
      during aphasia recovery and suggests several pathogenetic mechanisms that may
      contribute to the development of this syndrome.

PMID- 9161382
TI  - Controlling the spread of vancomycin-resistant enterococci with a rehabilitation
      cohort unit.
AB  - Enterococci are common to the human gastrointestinal tract. Recently there has
      been an emergence of vancomycin-resistant enterococci (VRE); infection requires
      strict contact isolation. Patients with VRE infections are at higher risk for
      morbidity and mortality. As a result of the high prevalence of VRE, it was
      recommended that a cohort unit be established to control its spread within our
      metropolitan community hospital. We report the development of a rehabilitation
      VRE cohort unit. We present case studies of five patients who developed
      nosocomial colonization and one with an infection with VRE; all were treated on
      the rehabilitation cohort unit. Protocols for VRE isolation and procedures for
      decontamination in the cohort unit were developed. If a cohort unit is necessary,
      it is feasible to conduct a rehabilitation program in a cohort unit with strict
      adherence to contact isolation.

PMID- 9161384
TI  - The history of physical medicine and rehabilitation as recorded in the diary of
      Dr. Frank Krusen: Part 4. Triumph over adversity (1954-1969).
AB  - This article, the last of four based on the diary of Dr. Frank H. Krusen, picks
      up the story of physiatry's conflict with other medical specialty groups within
      the American Medical Association. The conflict was focused on PM&R's use of the
      term "rehabilitation," but the underlying motive of groups opposing physical
      medicine was to limit the scope of physiatric practice. Dr. Krusen organized a
      well-documented and successful defense of the specialty and opened the door to
      the development of comprehensive care of persons with disabilities. Also related
      here are Dr. Krusen's legislative and public relations contributions to PM&R from
      1963 until his retirement from Tufts-New England Medical Center in 1969. Dr.
      Krusen retired to Cape Cod and died there in 1973.

PMID- 9161383
TI  - The history of physical medicine and rehabilitation as recorded in the diary of
      Dr. Frank Krusen: Part 3. Consolidating the position (1948-1953)
AB  - This article is a continuation of the story of the struggle to win recognition of
      physical medicine and rehabilitation as a medical specialty, as told in the pages
      of a daily diary kept by Frank H. Krusen, MD, from 1943 through 1967. The first
      two articles described Dr. Krusen's professional development before 1943, his
      efforts to establish a certifying Board for physiatrists, and the role of the
      Baruch Committee on Physical Medicine in Krusen's eventual successes. This
      article focuses on how Krusen and his physiatric colleagues campaigned to gain
      acceptance by organized medicine of the new specialty, to unite the fields of
      physical medicine and rehabilitation, and to identify and maintain the scope of
      physiatric practice despite challenges from other specialties.

PMID- 9161385
TI  - "Too early intervention" in back pain.

PMID- 9161386
TI  - Isometric strength data.

PMID- 9161387
TI  - Surgery in Israel.
AB  - The evolution and development of surgery in Israel reflects the influence of its
      dramatic historical events. The immigration of surgeons, particularly since the
      fourth decade of the 20th century, highly contributed to the framework of modern
      surgery. Medical education occurs at 4 medical schools, in Jerusalem, Tel Aviv,
      Haifa, and Beer Sheva, and postgraduate surgical training takes place in all
      public hospitals, most of which are university hospitals or have university
      affiliated departments, and is controlled by the Scientific Council of the Israel
      Medical Association (Tel Aviv). Health care is provided by 4 health insurance
      funds and has been recently influenced by the National Health Insurance Bill and
      the Bill of Patient's Rights. Surgical standards are high and similar to the very
      best of Western countries. The geographical location of Israel in the Middle
      East, surrounded by hostile Arab countries, has dramatically influenced the
      development of Israeli surgery. The practice of surgery ranges from full-time
      service in state and insurance-funded mostly academic hospitals, to private part
      time clinics for wealthy and insured patients. Surgical training occurs only in
      departments accredited by the Scientific Council, which are mostly affiliated
      with the 4 medical schools. A surgical residency in Israel usually requires 6
      years, and its guidelines and regulations are elaborated and recommended by the
      Israel Surgical Society and controlled by the Scientific Council. Most Israeli
      surgeons were trained in Israeli hospitals, but a substantial number of surgeons
      immigrated to the country, especially from eastern Europe.

PMID- 9161388
TI  - Brothers.

PMID- 9161389
TI  - Is esophagectomy following upfront chemoradiotherapy safe and necessary?
AB  - OBJECTIVE: To examine the safety and necessity of esophagectomy following upfront
      chemoradiotherapy (CRT) in patients with potentially resectable esophageal
      cancer. DESIGN: Cohort analytic study during a 4-year period. SETTING: Tertiary
      referral center. PATIENTS: Thirty-seven patients who completed CRT and underwent
      esophagectomy as compared with 30 patients who underwent esophagectomy alone
      without pretreatment during the same period. MAIN OUTCOME MEASURES: Resection
      related events, perioperative morbidity and mortality, response to CRT, site of
      residual disease following CRT, and survival of partial responders. RESULTS:
      Patients receiving CRT followed by esophagectomy were similar to patients who
      underwent esophagectomy alone for operative characteristics, postoperative
      course, and perioperative morbidity and mortality. Of the 33 patients who
      achieved an objective response to CRT, 23 had residual tumor in the resection
      specimen. Of the 18 patients alive with no evidence of disease at a median follow
      up of 30 months, 50% had residual tumor following CRT. CONCLUSIONS: Upfront CRT
      did not adversely affect resection-related outcome and may facilitate resection
      by downstaging disease. A considerable number of patients had prolonged survival
      after esophageal resection despite having residual tumor present following
      treatment with upfront CRT. Therefore, esophagectomy following upfront CRT can
      improve locoregional control of disease and should remain a critical component of
      any multimodality regimen.

PMID- 9161390
TI  - The role of antibiotic prophylaxis in severe acute pancreatitis.
AB  - OBJECTIVE: To assess the impact of intravenous (IV) antibiotic prophylaxis on the
      incidence of pancreatic infection and the mortality rate in severe acute
      pancreatitis. DESIGN: Restropective review of a cohort of 180 patients with
      severe acute pancreatitis. SETTING: A tertiary referral center in Sacramento,
      Calif. INTERVENTION: The use of IV antibiotic prophylaxis evolved during 3
      periods from no antibiotics in 50 patients (1982-1989), to nonprotocol use in 55
      patients (1990-1992), to a 4-week course of imipenem-cilastatin sodium (1993
      1996) given to 75 patients having Acute Physiology and Chronic Health Evaluation
      (APACHE) II scores greater than 6 and pancreatic necrosis (> 15% of the gland),
      peripancreatic necrosis, or peripancreatic collection. MAIN OUTCOME MEASURES:
      Pancreatic infection and mortality. RESULTS: Without antibiotic prophylaxis, the
      incidence of pancreatic infection was 76% (38/50). Intravenous antibiotic
      prophylaxis reduced the infection rate of 45% (25/55) (P = .03). The imipenem
      cilastatin protocol further reduced the infection rate to 27% (20/75) (P = .04).
      The mortality rates showed only a decreasing trend, from 16% (1982-1989) to 7%
      (1990-1992) to 5% (1993-1996) (P = .11). Patients with sterile severe acute
      pancreatitis had a mortality rate of 2% (2/97); whereas 17% (14/83) of patients
      with infection succumbed to the disease. Patients developing infection within the
      first 4 weeks from the onset of illness had mortality rates ranging from 19% to
      40%, compared with 0% to 8% for those who became infected after 4 weeks. No
      patient with pancreatic infection developing after 4 weeks died with the imipenem
      cilastatin protocol. CONCLUSIONS: Intravenous antibiotic prophylaxis
      significantly reduced the infection rate in severe acute pancreatitis, with only
      a trend toward improved survival. A prospective, randomized, double-blind
      multicenter trial comparing the efficacy of different types and/or combinations
      of antibiotic prophylaxis in severe acute pancreatitis is indicated.

PMID- 9161391
TI  - Spectrum of general surgery in rural America.
AB  - OBJECTIVES: To define the types of surgery performed by rural surgeons, to
      compare their experience to that of graduating US surgical residents and to
      document rural surgical mortality. DESIGN: Prospective registry of consecutive
      cases recorded by 7 rural general surgeons working in one department of surgery
      from December 31, 1994, through March 30, 1996. Comparison with the 1995 Report C
      (Resident Operative Logs) of the Residency Review Committee. National survey of
      surgical residency programs regarding formal gynecology experience. SETTING: Nine
      rural community hospitals in the Midwest. PATIENTS: Patients undergoing surgery
      in 9 cities with populations of fewer than 10000. MAIN OUTCOME MEASURES: Type of
      surgery and postoperative (30-day) mortality. RESULTS: Two thousand four hundred
      twenty procedures were performed by 7 surgeons practicing in 9 cities with
      populations of 1500 to 8000. There were 6 (0.25%) postoperative deaths. Case
      types are as follows: endoscopy, 686 (28.3%); gynecology, 498 (20.6%); hernia,
      241 (10%); colorectal, 194 (8%); biliary, 183 (7.6%); cesarean sections, 130
      (5.4%); breast, 129 (5.3%); orthopedic, 115 (4.8%); carpal tunnel, 63 (2.6%);
      otolaryngology, 35 (1.4%); and endocrine, 1 (0.4%); for a total of 2420 (100%).
      Report C indicated 1995 graduating chief residents averaged 8 obstetric and and
      gynecologic and 5.3 orthopedic cases during their residency. Of 204 surgical
      residency programs surveyed, 106 (52%) offered no obstetrics and gynecology
      rotation. CONCLUSIONS: A large volume of surgery was performed with low mortality
      by 7 rural general surgeons. The operative experience of 1995 residency graduates
      differed from our rural surgeons. We recommend a rural surgical track in selected
      training programs to prepare graduates better for rural practice. Senior level
      rotations in endoscopic, gynecologic, obstetric, and orthopedic surgery and
      mentorship with rural surgeons would be optimal.

PMID- 9161392
TI  - A randomized, prospective trial of deep venous thrombosis prophylaxis in aortic
      surgery.
AB  - OBJECTIVES: To study the incidence of postoperative deep venous thrombosis (DVT)
      in patients undergoing elective aortic reconstruction and to determine if
      aggressive DVT prophylaxis would reduce the incidence of DVT in these patients.
      DESIGN: Randomized, prospective trial. SETTING: University hospital and Veterans
      Affairs hospital. PATIENTS: One hundred patients undergoing aortic reconstruction
      for aneurysmal or occlusive disease randomized to receive DVT prophylaxis
      (treatment group) or no prophylaxis (control group). Exclusion criteria included
      a history of DVT, long-term anticoagulant use, or a malignant neoplasm. During
      the study period, 12 patients were ineligible for follow-up. Ninety-eight
      patients completed the trial, including 50 patients in the treatment group and 48
      patients in the control group. Two patients in the control group died
      postoperatively of unrelated causes. INTERVENTION: Patients in the treatment
      group received DVT prophylaxis using a combination of low-dose heparin sodium
      therapy (5000 U every 12 hours) and calf-length intermittent mechanical
      compression devices. Control patients received no DVT prophylaxis. MAIN OUTCOME
      MEASURES: The occurrence of acute lower extremity DVT diagnosed by interval
      venous duplex ultrasound scan surveillance performed on postoperative days 1, 3,
      and 7. RESULTS: The overall incidence of proximal DVT in this study was 2%. One
      case of DVT occurred in the treatment group, and the other one occurred in the
      control group. There was no statistically significant difference (P = .99) in the
      incidence of DVT between the 2 groups. One patients in the control group had a
      nonfatal pulmonary embolus (1% of the patients overall). CONCLUSIONS: The
      incidence of proximal DVT in patients undergoing elective aortic reconstruction
      is low compared with patients undergoing other major intraabdominal general
      surgical procedures. The use of aggressive DVT prophylaxis did not reduce the
      risk of postoperative proximal DVT in this study. The selective use of DVT
      prophylaxis in patients undergoing elective aortic surgery should be based on
      associated concomitant or evolving risk factors.

PMID- 9161393
TI  - Hepatic resection for metastatic colorectal cancer results in cure for some
      patients.
AB  - OBJECTIVES: To determine the long-term disease-free and overall survivals for
      patients undergoing hepatic resection for colorectal cancer metastases and to
      define significant predictors of improved patients survival. DESIGN:
      Retrospective review. SETTING: Single tertiary care center. PATIENTS: Two hundred
      eighty consecutive patients underwent hepatic resection for colorectal cancer
      metastases at the Mayo Clinic from 1960 to 1987. Fifty patients alive at the
      completion of the study had a mean follow-up of 11.3 years (median, 121 months).
      MAIN OUTCOME MEASURES: Disease-free interval following initial hepatic resection
      and death. RESULTS: The overall 5-year survival of the 280 patients was 27%.
      Twenty-eight patients were alive at 10 years from the time of hepatic resection,
      and the 10-year actuarial survival was 20%. Only 2 patients alive and free of
      disease at 5 years had recurrent disease. For all other patients who were free of
      disease more than 5 years after hepatic resection and died, the cause of death
      was not cancer related. No patients characteristics or features of the primary
      tumor affected survival. Clinical presentation of metastatic disease,
      configuration of hepatic lesions, the presence of extrahepatic lymph node
      involvement, and the existence of resectable extrahepatic disease significantly
      affected long-term patient survival. Need for perioperative blood product
      transfusion was associated with a lower probability of long-term survival.
      CONCLUSIONS: Disease-free patient survival beyond 5 years from surgical resection
      of colorectal cancer metastases to the liver represents patient cure in nearly
      all instances.

PMID- 9161394
TI  - Stereotactic core needle biopsy and the workup of mammographic breast lesions.
AB  - OBJECTIVE: To evaluate the influence of stereotactic core needle biopsy (SCNB) as
      an alternative to wire localization biopsy (WLB) on the evaluation and workup of
      nonpalpable mammographic lesions. DESIGN: A 4-year retrospective clinical review.
      SETTING: University hospital and clinics. PATIENTS: All patients evaluated for
      nonpalpable mammographic lesions after screening, diagnostic mammography, or both
      during the 4-year period of the study were included. OUTCOME PARAMETERS: Changes
      in the number and types of mammograms and diagnostic biopsies and the histologic
      findings using each technique (SCNB vs WLB), including total number of cancers
      diagnosed. RESULTS: The number of screening mammograms and WLBs performed
      remained constant compared with a marked increase in the number of diagnostic
      mammograms and SCNBs. The rates of positive findings for each biopsy technique
      were consistent while the total number of cancers diagnosed increased
      dramatically. The percentage of biopsy specimens with positive results (ductal
      carcinoma in situ and invasive cancers) for SCNB was 13.3% compared with 26.2%
      for WLB specimens. There has also been an increase in the number of cancers
      found, from 22 in the first year to 54 in the fourth year. In the first year, 45%
      of these cancers were diagnosed by SCNB; in the fourth year, 83% of the cancers
      were diagnosed by SCNB. CONCLUSION: Stereotactic core needle biopsy has replaced
      WLB as the standard for the diagnostic biopsy of suspicious, nonpalpable
      mammographic lesions. Since adopting this technique, more patients have been
      examined and their conditions diagnosed as breast cancer in an efficient, cost
      effective manner.

PMID- 9161395
TI  - Early postoperative feeding after elective colorectal surgery.
AB  - BACKGROUND: Several investigators have demonstrated that routine nasogastric
      decompression after abdominal surgery is unnecessary and can be safely
      eliminated, and 1 recent study demonstrated the safety of early oral feedings.
      OBJECTIVE: To test the hypothesis that successful early feeding would lead to a
      shorter duration of hospitalization and, therefore, would be more cost-effective.
      PATIENTS: Fifty-eight patients with elective colorectal surgery. METHODS:
      Patients were prospectively randomized to 1 of 2 postoperative treatment arms:
      early feeding (EF group, n = 29) and traditional feeding (TF group, n = 29). All
      patients in the EF group began a liquid diet on the first postoperative day and
      were advanced to a regular diet when they consumed 1000 mL in 24 hours. All
      patients in the TF group began a liquid diet after resolution of the
      postoperative ileus and were advanced to a regular diet after consuming 1000 mL
      in 24 hours. Patients were dismissed after tolerating two thirds of the regular
      diet. Both groups had intraoperative orogastric tubes that were removed at the
      end of surgery. Nasogastric tubes were inserted for persistent postoperative
      vomiting. RESULTS: No significant differences were noted in age, types of
      procedures, or in prior abdominal surgery in either group. No significant
      differences were seen in rates of nausea (55% in EF vs 50% in TF group) or
      vomiting (48% in EF vs 33% in TF group). One patient in the EF group had
      aspiration pneumonia, and anastomotic leak resulted in sepsis and eventual death
      of 1 patient in the TF group. No significant difference was observed in length of
      hospital stay between the 2 groups (mean +/- SD, 7.2 +/- 3.3 days in EF vs 8.1 +/
      2.3 days in TF group). CONCLUSIONS: Early oral feeding after elective colorectal
      surgery is safe. Most of the patients tolerated EF; however, there was no
      significant difference in duration of hospitalization in these patients.

PMID- 9161396
TI  - Sartorius myoplasty for infected vascular grafts in the groin. Safe, durable, and
      effective.
AB  - OBJECTIVE: To review the safety, durability, and efficacy of sartorius myoplasty
      in the treatment of localized vascular prosthetic graft infection in the groin.
      DESIGN: Case series. SETTING: University teaching hospitals. PATIENTS: Fourteen
      patients with 15 exposed, eroded, or overtly infected prosthetic vascular grafts
      in the groin, treated during 7 years. INTERVENTIONS: Groin exploration for
      delineation of the extent of vascular graft infection, followed by extensive
      perigraft debridement, then dissection and rotation of the ipsilateral sartorius
      muscle to cover the involved graft. MAIN OUTCOME MEASURES: Healing of groin wound
      with preservation of vascular graft function, limb salvage, length of hospital
      stay, impact of specific wound bacteria, and evidence of long-term hip
      dysfunction. RESULTS: During a mean hospital stay of 8.7 days, sartorius
      myoplasty was accomplished with 20% morbidity. Hip flexor function was initially
      impaired in all 14 patients, but functional deficit was negligible at late
      assessment. During mean follow-up of 36 months, all wounds were healed, and all
      limbs were salvaged. Two late deaths occurred, and 2 limbs were ultimately
      amputated due to progressive loss of vascular outflow. CONCLUSION: Sartorius
      myoplasty is a simple, safe, durable, and effective technique for preservation of
      locally infected or exposed vascular grafts in the groin.

PMID- 9161397
TI  - Upper extremity ischemia from subclavian artery aneurysm caused by bony
      abnormalities of the thoracic outlet.
AB  - OBJECTIVE: To describe our experience with surgical therapy for upper extremity
      ischemia incident to emboli from aneurysms of the subclavian artery. DESIGN:
      Retrospective review case series. SETTING: Vascular surgery practice at a
      university hospital-based tertiary referral center. PATIENTS: All patients
      treated for upper extremity ischemia caused by embolism from a subclavian artery
      aneurysm from January 1, 1990, to July 31, 1996. INTERVENTION: All patients
      underwent detailed history and physical examination, screening for immunologic
      and hypercoaguable disorders, noninvasive vascular laboratory evaluation, and
      arteriography of the aortic arch in both arms and hands. Surgical treatment
      consisted of rib excision or fracture plating, aneurysm excision, and
      interposition vein grafting, with additional saphenous vein bypasses to brachial
      or forearm arteries as needed to provide uninterrupted circulation to the wrist.
      RESULTS: Twelve patients (6 males; mean age, 37 years) were treated. All had
      episodic upper extremity ischemia with an initial misdiagnosis of primary
      vasospastic disorder. Rest pain and/or ischemic ulceration developed in 3.
      Duration of symptoms before correct diagnosis averaged 7 months (range, 1-36
      months). All patients had bony abnormalities of the thoracic outlet (8 cervical
      ribs, 3 abnormal first ribs, and 1 unstable clavicular fracture). All aneurysms
      contained intraluminal thrombus, and all patients had multiple ipsilateral distal
      arm, forearm, and/or hand arterial occlusions indicating chronic and repeated
      embolization. All patients underwent aneurysm excision and interposition vein
      grafting, with additional vein bypass to the brachial (3 patients) and/or forearm
      arteries (5 patients). Mean follow-up was 18 months (range, 2 weeks to 63
      months). Eleven patients had complete symptomatic relief, and 1 patient improved.
      All subclavian interposition grafts remained patient. Two distal bypass grafts
      occluded in patients with preoperative arteriograms demonstrating no patient
      forearm arteries. There has been no limb loss. CONCLUSIONS: Hand ischemia caused
      by embolization from a subclavian artery aneurysm occurs in young patients
      without atherosclerosis and is frequently misdiagnosed as vasospasm. Despite
      advanced disease and multiple chronic distal arterial occlusions, surgical
      treatment by resection of bony abnormalities, aneurysm excision and grafting, and
      distal bypass grafting produces excellent results.

PMID- 9161398
TI  - Elimination of various subpopulations of macrophages and the development of
      multiple-organ dysfunction syndrome in mice.
AB  - OBJECTIVE: To evaluate the role of specific macrophage subpopulations in the
      development of zymosan-induced multiple-organ dysfunction syndrome by selective
      elimination of liver, splenic, alveolar, and peritoneal macrophages. DESIGN:
      Randomized animal trial. SETTING: Central animal laboratory at the University
      Hospital Nijmegen, Nijmegen, the Netherlands. ANIMALS: Male C57Bl/6 mice.
      INTERVENTIONS: Elimination of macrophages was accomplished by administration of
      multilamellar liposomes that contained dichloromethylene bisphosphonate (Cl2MBP).
      Intravenous, intratracheal, and intraperitoneal administrations induced an
      elimination of liver and splenic, alveolar, and peritoneal and omental
      macrophages, respectively. Zymosan (1 mg/g) was injected intraperitoneally at day
      0. The liposomes that contained Cl2MBP were administered before and after zymosan
      challenge. At day 12, all surviving mice were killed. MAIN OUTCOME MEASURES: The
      body weights, temperatures, and mortality rates of the mice were monitored daily.
      Relative organ weights (ROWs) were calculated from the lungs, liver, spleen, and
      kidneys after the mice were killed. RESULTS: The liposomes that contained Cl2MBP,
      administered intravenously before or after zymosan challenge, did not induce
      significant changes in the body weight, temperature, or mortality rate. The ROW
      of the liver was significantly decreased in both treatment groups. Elimination of
      liver and splenic macrophages after zymosan challenge induced an increased ROW of
      the lung and a decreased ROW of the liver. The liposomes that contained Cl2MBP,
      administered intratracheally before zymosan challenge, completely prevented
      deaths. The body weights, temperatures, and ROWs of the mice were not changed.
      The liposomes that contained Cl2MBP, administered intraperitoneally, did not
      change the body weight, temperature, or ROW. The liposomes that contained Cl2MBP,
      administered intraperitoneally before zymosan challenge, increased the mortality
      from 50% to 90%. CONCLUSIONS: These data show that the elimination of specific
      macrophage subpopulations and the elimination on specific time points in this
      model had differential effects, indicating a differential role of specific
      macrophage subpopulations, either protective or detrimental, in the development
      of multiple-organ dysfunction syndrome.

PMID- 9161399
TI  - Vessel counts and expression of vascular endothelial growth factor as prognostic
      factors in node-negative colon cancer.
AB  - BACKGROUND: The value of these prognostic factors was compared with that of other
      clinicopathologic factors such as tumor grade, tumor stage, mucin production,
      vascular invasion, perineural invasion, and lymphatic invasion. OBJECTIVE: To
      determine whether the development of distant recurrence in patients with node
      negative colon cancer could be predicted using vessel count and vascular
      endothelial growth factor (VEGF) expression. DESIGN: Paraffin-embedded colon
      cancers were immunostained for factor VIII, VEGF, basic fibroblast growth factor,
      and proliferating cell nuclear antigen; slides were reviewed for differentiation,
      mucin production, and the presence of vascular, lymphatic, and/or perineural
      invasion. SETTING: A large academic cancer referral center where 27 patients with
      node-negative colon cancer were operated on during 1988 and 1989. MAIN OUTCOME
      MEASURE: The development of and interval to recurrence. RESULTS: Eight patients
      developed liver, lung, or lymph node metastases at a median of 24 months. The
      median follow-up for patients without cancer recurrence was 60 months. The mean
      tumor vessel count for those patients who remained disease-free was significantly
      fewer than for those patients who suffered a recurrence (20 vs 33, respectively).
      By univariate analysis, 3 factors- perineural invasion, vessel count, and VEGF
      expression- were correlated with time to recurrence. By multivariate analysis,
      only vessel count was significantly related to differences in time to recurrence.
      Expression of VEGF correlated with vessel count. CONCLUSION: Vessel count and
      expression of VEGF may be useful for predicting distant recurrence in patients
      with node-negative colon cancer.

PMID- 9161400
TI  - Measurement of gastrointestinal intramucosal pH is a poor guide to tolerable
      levels of anemia during isovolemic hemodilution in a canine model of coronary
      stenosis.
AB  - OBJECTIVE: To determine the relationship between gastrointestinal intramucosal pH
      and myocardial oxygenation during isovolemic hemodilution in dogs with critical
      coronary artery stenoses. DESIGN: Prospective sequential evaluation of ileal
      intramucosal pH and regional myocardial function of a critically perfused area of
      myocardial tissue in a canine model of normovolemic hemodilution. SETTING: A
      research laboratory. SUBJECTS: Fifteen dogs. INTERVENTIONS: A micrometer snare
      was placed around a main coronary artery (8 left anterior descending artery, 7
      right coronary artery). Three pairs of sonomicrometer crystals were placed in the
      heart to measure regional myocardial contraction. A gastrointestinal tonometer
      was placed in the ileum and used to measure luminal PCO2. This PCO2 value was
      used to calculate the ileal intramucosal pH. The animals underwent normovolemic
      hemodilution until myocardial ischemia occurred in the region supplied by the
      snared vessel. Measurements were continued for a further 40 minutes. MEASUREMENTS
      AND MAIN RESULTS: Following instrumentation, stabilization, and critical
      constriction of a coronary vessel, percentage changes in systolic shortening of
      myocardial tissue in the region of critical perfusion were determined every 20
      minutes. Ileal intramucosal pH and commonly measured cardiovascular variables
      were determined at the same time points. Myocardial ischemia occurred after 80
      minutes of hemodilution, when the mean (+/- SD) hemoglobin concentration had
      fallen from a baseline level of 123 +/- 18 g/L to 82 +/- 14 g/L (P < .01). From
      the start of hemodilution to 40 minutes after myocardial ischemia occurred, there
      were no significant changes in heart rate, cardiac output, oxygen consumption,
      arterial acid-base balance, or arterial PCO2. Oxygen delivery decreased by
      approximately 45% (5.99 +/- 1.66 to 3.41 +/- 0.90 mL/kg per minute; P < .01) but
      there were no changes in ileal intramucosal pH (7.31 +/- 0.08 to 7.30 +/- 0.08; P
      = .90). CONCLUSIONS: Myocardium compromised by coronary stenosis is more
      sensitive to normovolemic hemodilution-induced ischemia than the normally
      perfused gut mucosa. This limits the potential utilization of the measurement of
      gastrointestinal intramucosal pH as a guide to tolerable levels of anemia in
      critically ill patients.

PMID- 9161401
TI  - Complete regression of primary cutaneous malignant melanoma.
AB  - While partial spontaneous histopathological regression is a common finding in
      invasive primary melanoma, proven complete regression is rare, with only 33 cases
      having been documented. None of the patients in these reported cases had a biopsy
      specimen taken from the original lesion, which would unequivocally prove the
      diagnosis of complete regressing melanoma. Over 4 years, we saw a 62-year-old
      white man who refused treatment of a biopsy specimen-proved superficial spreading
      melanoma (Breslow thickness, 0.7 mm) that eventually regressed completely. A
      biopsy specimen confirmed complete histopathological regression. There was no
      clinical evidence of regional or distant metastases throughout the 4 years. To
      our knowledge, this is the first documented case of a biopsy specimen-proved
      primary melanoma completely regressing. We present sequential photographic
      documentation and review the literature about this phenomenon. While the
      prevalence of such an event is unknown, evidence is presented that it may be more
      common than previously thought.

PMID- 9161402
TI  - The myth of managed care.

PMID- 9161403
TI  - Organization, structure and alternate splicing of the murine RFC-1 gene encoding
      a folate transporter.
AB  - The structural organization of the murine RFC-1 gene encoding a folate
      transporter has been determined. The entire nucleotide sequence of the L1210 cell
      RFC-1 cDNA, the 3'- and 5'-untranslated regions and the coding sequence were
      found to be distributed in eight exons, including six primary exons and
      alternates to exon 1 and exon 5, spanning 10.4 kb. Splice variants were
      identified in an L1210 cell cDNA library. The most common incorporates exons 1
      through 6, encoding a 58-kDa polypeptide. The two least common incorporate exons
      1 and 2, a truncated version of exon 3 and exons 4 through 6; or exons 1 through
      4, an alternate to exon 5, and exon 6, encoding polypeptides of 53.6 and 43.4
      kDa, respectively. A fourth variant reported earlier (GenBank/EMBL accession No.
      L36539) by others incorporates what we have found to be an alternate of exon 1
      and exons 2 through 6. A relatively GC-rich region of the genome just 5' of exon
      1 as well as exon 1a appears to be distinctly promoter-like and encodes a number
      of putative cis-acting elements. The findings pertaining to alternates of exon 1
      suggest that the transcription of RFC-1 variants results from two different
      promoters.

PMID- 9161404
TI  - Transcriptional regulation of tracheo-bronchial mucin (TBM) gene by ethanol.
AB  - The epithelia of the respiratory tract are protected by a mucin glycoprotein. The
      expression of mucin changes when epithelia come in contact with toxic agents such
      as ethanol. Previously, we have identified and characterized the expression of a
      tracheo-bronchial mucin (TBM) gene. In the present study, we observed that
      ethanol regulates TBM expression at the transcription level. Ethanol enhanced the
      expression of TBM mRNA in a dose- and time-dependent manner in HBE1 cells. At 100
      mM concentration (a concentration reported to be present in alcoholics), ethanol
      induced an eight-fold increase in TBM transcription as determined by reporter
      gene expression analysis.

PMID- 9161405
TI  - Satellite DNA from the brine shrimp Artemia affects the expression of a flanking
      gene in yeast.
AB  - We have previously revealed that in the brine shrimp Artemia franciscana an AluI
      DNA family of repeats, 113 bp in length, is the major component of the
      constitutive heterochromatin and that this repetitive DNA shows a stable
      curvature that confers a solenoidal geometry on the double helix in vitro. It was
      suggested that this particular structure may play a relevant role in determining
      the condensation of the heterochromatin. In this report we have cloned hexamers
      of highly-repetitive sequence (AluI-satellite DNA) in proximity to a yeast lacZ
      reporter gene on a plasmid. We find that the expression of the reporter gene is
      affected by the presence of this DNA in a dose- and orientation-dependent manner
      in the yeast, S. cerevisiae. We show that this effect is not dependent on under
      replication or re-arrangements of the repetitive DNA in the cell but is due to
      decreased expression of the reporter gene. Our results indicate that the AluI
      satellite DNA of Artemia per se is able to influence gene expression.

PMID- 9161406
TI  - Cloning of apg-2 encoding a novel member of heat shock protein 110 family.
AB  - Chinese hamster heat shock protein 110-encoding gene (hsp110), mouse apg-1 and
      human hsp70RY are structurally related genes, with the first two encoding about
      110-kDa HSPs [Yoon et al. (1995) J. Biol. Chem. 270, 15725-15733; Kaneko et al.
      (1997) J. Biol. Chem., in press; Fathallah et al. (1993) J. Immunol. 151, 810
      813]. Using apg-1 cDNA as a probe, we isolated a novel cDNA, apg-2 from a mouse
      testis cDNA library, which was highly homologous to human hsp70RY. However, the
      predicted amino acid (aa) sequence of APG-2 was longer (841 aa) than that of
      HSP70RY (701 aa) and comparable to those of HSP110 and APG-1. Northern blot
      analysis revealed that the expression of apg-2 transcripts was ubiquitous in
      various mouse tissues, and most abundant in the testis and ovary. While induction
      of hsp70 transcripts was observed in mouse TAMA26 Sertoli cells and NIH/3T3
      fibroblasts on temperature shift from 37 degrees C to 42 degrees C (traditional
      heat shock) or from 32 degrees C to 39 degrees C, apg-2 transcripts were not
      induced under either condition. These results suggest that apg-2 is an isoform of
      mouse homolog of hsp70RY, but that it belongs to the hsp110 family instead of
      hsp70 family, and that it plays a role under non-stress conditions.

PMID- 9161407
TI  - Isolation of a full-length human WNT7A gene implicated in limb development and
      cell transformation, and mapping to chromosome 3p25.
AB  - The Wnt gene family has a role in development as well as tumourigenesis. One
      mouse member, Wnt7a, is vital for limb development in vivo and also possesses
      transforming ability in vitro. This study reports the isolation of a full length
      of human homologue of mouse Wnt7a gene by library screening. Yeast artificial
      chromosome-fluorescence in situ hybridisation (YAC-FISH) mapped the WNT7A gene to
      chromosome 3p25. Human WNT7A had an ORF encoding a deduced protein of 349 aa that
      exhibited 97% and 92% identity to mouse Wnt7a at the aa and nucleic acid levels,
      respectively. It possessed the 22 conserved cysteine residues and 3 more at the
      amino terminus, and a putative poly A tail. This is the fifth human WNT gene in
      which a complete cDNA sequence had been determined.

PMID- 9161408
TI  - A Francisella tularensis DNA clone complements Escherichia coli defective for the
      production of Era, an essential Ras-like GTP-binding protein.
AB  - We cloned the era gene of Francisella tularensis from a plasmid library by
      heterologous genetic complementation of an Escherichia coli mutant conditionally
      defective for the production of Era, an essential protein for cell growth.
      Nucleotide sequence analysis indicated that, in F. tularensis, era constitutes a
      single gene operon. ORFs aspC and mdh encoding aspartate aminotransferase and
      malate dehydrogenase, respectively, flank era in F. tularensis. Although
      classified as Gram-, the flanking regions and the relative location of era in F.
      tularensis are distinctly different from those of typical Gram- and Gram+
      bacteria. Computer analysis of bacterial Era protein sequences identified
      conserved domains in addition to the common G domains of most GTP-binding
      proteins.

PMID- 9161409
TI  - The Rex phenotype of altruistic cell death following infection of a lambda
      lysogen by T4rII mutants is suppressed by plasmids expressing OOP RNA.
AB  - The coordinate expression from induced lambda prophages of pLit-rexB-tImm (late
      immunity transcription, LIT RNA) and po-oop-t(o) (OOP RNA) has remained
      unexplained. The initial assigned sequence for pLit bore no relationship to po.
      We have identified two promoter sites for independent rexB transcription, denoted
      here pLit2 and pLit1, which are separated by about 330 bp. The upstream pLit1
      site shares with po a common 9 bp sequence between the -10 and -35 regions, with
      strong homology to aspects of the SOS box or LexA operator site. This sequence is
      also found within OOP RNA, suggesting that OOP RNA, or another regulatory factor
      recognizing the common sequence, was involved in the regulation of rexB
      expression and hence Rex exclusion. We measured the influence of OOP synthesis
      from plasmids on the Rex phenotype, finding that plasmids producing OOP can
      suppress Rex exclusion by a lambda prophage. The possibility was suggested that
      low level constitutive rexB transcription occurs from pLit2. Potential binding
      sites were identified for DnaA, for the LexA, CI and Cro repressors and for
      lambda O protein in the 80 nt DNA interval upstream from and including pLit1,
      suggesting a complex regulatory pattern for rexB expression from this promoter.

PMID- 9161410
TI  - A novel HSP70 gene of Schizosaccharomyces pombe that confers K-252a resistance.
AB  - A new gene encoding a heat shock protein 70 family protein of Schizosaccharomyces
      pombe (Sp), named sks2+, was cloned as a weak suppressor for the K-252a-sensitive
      mutation, ucm1. The nucleotide sequence of sks2+ revealed an open reading frame
      of a 613-amino-acid (aa) protein. The deduced aa sequence of sks2+ showed
      significant homology with Saccharomyces cerevisiae (Sc) Ssb1p and Ssb2p
      responsible for protein synthesis by non-organelle-localized ribosomes, as well
      as with other proteins of the HSP70 family. The cells lacking the functional
      sks2+ gene were viable and showed no increased sensitivity to K-252a but grew
      slowly with an elongated morphology. These results suggest that the sks2+ gene
      product plays a role in the cell cycle progression and is able to confer drug
      resistance in a multicopy state.

PMID- 9161411
TI  - Antisense-mediated regulation of Annexin VII gene expression during the
      transition from growth to differentiation in Dictyostelium discoideum.
AB  - Annexin VII is believed to be required for proper Ca(2+)-homeostasis in
      Dictyostelium discoideum cells. As was previously reported, the expression of
      Annexin VII gene increased during the transition of D. discoideum Ax-2 cells from
      growth to differentiation. We have casually cloned an interesting gene, Quit3, by
      the differential plaque hybridization. Quit3 had no coding region, and was
      expressed more predominantly in the growth phase than in the differentiation
      phase. Unexpectedly, this gene was found to encode the complementary sequence of
      Annexin VII. Therefore, it is most likely that the Quit3 mRNA may regulate the
      Annexin VII synthesis by the natural antisense transcript via an antisense RNA
      RNA interaction, thus resulting in striking increase of Annexin VII production in
      the phase-shift of cells from growth to differentiation. Since Annexin VII is
      known to be coded for by a single gene in Dictyostelium, the antisense RNA seemed
      to be encoded in the same genetic locus as the Annexin VII mRNA.

PMID- 9161413
TI  - Correlation of the exon/intron organization to the secondary structures of the
      protease domain of mouse meprin alpha subunit.
AB  - Metalloendopeptidases of the astacin family contain a homologous protease domain
      of about 200 amino acids. We now report the genomic structure corresponding to
      the protease domain for one member of this family, the mouse meprin alpha
      subunit. This is the first such description for the mammalian meprin subunits. It
      consists of four small exons (76 to 222 base pairs) and three large introns (2.9
      to 4.2 kilobases). The exon/intron organization correlates well with the
      secondary structure elements of the domain as predicted by computer modeling.
      Exon Ep1 contains beta strand I, and Ep2 consists of helix A and beta strands II
      III. Ep3 corresponds to beta strands IV-V and helix B. Ep4 correlates with
      helices C and D. Introns Ip1 and Ip2 are present at the beginning of helix A and
      beta strand IV, respectively, and Ip3 is between helices B and C. Similar
      analyses of sequences previously published by others, have extended this
      correlation to other astacin family members from different organisms. The
      relationship between gene and protein structures within the astacin family
      provide novel information on the evolution of this family in relation to other
      gene families.

PMID- 9161412
TI  - Genomic structure and expression analyses of serine acetyltransferase gene in
      Citrullus vulgaris (watermelon).
AB  - The genomic clones of Sat gene encoding serine acetyltransferase (SATase), a key
      enzyme in cysteine biosynthesis in plants, were isolated from the genomic library
      of Citrullus vulgaris (watermelon). The determination of nucleotide sequence of
      5.7 kilobase pair (kbp) length revealed the presence of two introns of 1939
      basepair (bp) and 515 bp length in the gene. The transcription start point was
      determined by primer extension experiments. Southern blot analysis indicated the
      presence of a single copy of the Sat gene and a couple of additional related
      sequences in the genome of C. vulgaris. The expression of Sat was analyzed in
      watermelon plants growth under sulfur- and/or nitrogen-starved conditions and in
      the presence of pyrazole, O-acetylserine and N-acetylserine. Only slight
      increment (ca. 1.5-2-fold) of Sat gene expression was observed upon sulfur
      starvation for 48 h. Interestingly, the addition of pyrazole, which is a
      precursor of beta-pyrazolealanine (beta-PA) synthesized by SATase and
      cysteine/beta-PA synthase, enhanced the expression of Sat by ca. 2-fold.

PMID- 9161414
TI  - Cloning and analysis of a cDNA encoding a two-domain hemoglobin chain from the
      water flea Daphnia magna.
AB  - A cDNA encoding a two-domain hemoglobin (Hb) chain of Daphnia magna was cloned
      and its nucleotide (nt) sequence of 1261 bp was determined. The nt sequence
      contained 74 bp of the leader sequence, 1047 bp of an open reading frame (ORF),
      and 119 bp of the 3'-untranslated region (UTR), excluding the polyadenylation
      tail. A sequence, AATACA, located 24 bp upstream from the polyA sequence was
      considered to be a polyadenylation signal. cDNA-derived amino acid (aa) sequence
      revealed that D. magna Hb chain is synthesized as a secretory precursor with a
      signal peptide of 18 aa. Mature D. magna Hb chain consists of 330-aa residues
      with a calculated molecular weight of 36227, which is composed of two large
      repeated domains, domain 1 and 2. Several key aa that are invariant in all or
      most of other Hb and required for functional heme-binding are conserved in each
      of the two domains. The N-terminal extension (pre-A segment) of domain 1 was
      unusually long and contained an unusual threonine-rich sequence. The homology
      between the aa sequences of the two domains (24% identity) was much lower than
      that observed in other two-domain Hb chains from clams or nematode. Hb mRNA level
      in D. magna reared under low oxygen concentration was more than 12 times higher
      than that in D. magna reared with sufficient aeration, indicating that the
      expression of Hb gene is regulated by mRNA level.

PMID- 9161415
TI  - Molecular cloning and expression of the large subunit of ADP-glucose
      pyrophosphorylase from barley (Hordeum vulgare) leaves.
AB  - A cDNA clone, blpl14, corresponding to the large subunit of ADP-glucose
      pyrophosphorylase (AGPase), has been isolated from a cDNA library prepared from
      leaves of barley (Hordeum vulgare L.). An open reading frame encodes a protein of
      503 aa, with a calculated molecular weight of 54815. The derived aa sequence
      contains a putative transit peptide sequence, required for targeting to plastids,
      and has a highly conserved positioning of critical Lys residues that are believed
      to be involved in effector binding. The derived aa sequence shows 97% identity
      with the corresponding protein from wheat, but only 36% identity with AGPase from
      E. coli. The blpl14 gene is expressed predominantly in leaves and to a lesser
      degree in seed endosperm, but not roots, of barley.

PMID- 9161416
TI  - Cloning of a single-chain variable fragment (scFv) switching active plasminogen
      activator inhibitor-1 to substrate.
AB  - Increased levels of plasminogen activator inhibitor-1 (PAI-1) are a well-known
      risk for cardiovascular diseases. A significant number of investigations are
      aimed at lowering plasma levels of PAI-1 to enhance endogenous fibrinolysis. We
      have recently generated monoclonal antibodies that neutralize PAI-1 activity by
      switching the inhibitory conformation to a substrate conformation. However,
      intact murine antibodies have quite some disadvantages for therapeutic use in
      man. In the current study, we describe the construction of a smaller antibody
      fragment derived from a monoclonal antibody (MA-8H9D4) with PAI-1 neutralizing
      properties. The cDNAs encoding the variable domains of the heavy and light chain
      were amplified, linked and cloned into a phagemid vector. Resulting clones were
      expressed as a single-chain variable fragment (scFv, VH-(Gly4Ser)3-VL) on the
      surface of a phage and selected for binding to PAI-1. Subsequently, a positive
      phage was used for the production of soluble scFv-8H9D4. Following purification,
      the characteristics of the scFv-8H9D4 were compared to those of the original MA
      8H9D4. The scFv inhibited PAI-1 activity to a similar extent as MA-8H9D4 and by a
      similar mechanism, i.e., induction of a conformational switch. Thus, this smaller
      antibody fragment, exhibiting the same properties as the parent molecule may
      constitute a useful starting point for the design of PAI-1 neutralizing
      therapeutics.

PMID- 9161417
TI  - Human aldehyde dehydrogenase genes, ALDH7 and ALDH8: genomic organization and
      gene structure comparison.
AB  - The structure of two human aldehyde dehydrogenase genes, ALDH7 and ALDH8, have
      been determined. The ALDH7 gene spans about 20 kb of the human genomic DNA and is
      composed of 9 coding exons. The ALDH8 gene is over 10 kb in length and consists
      of at least 10 exons. The ALDH8 gene contains an in-frame stop codon at the 17th
      codon position from the first initiator Met. The coding region of the ALDH7 gene
      shows about 86% nucleotide identity with the corresponding region of the ALDH8
      gene. The numbers and positions of the introns of the two genes are conserved,
      suggesting that gene duplication is involved in the expansion of the ALDH gene
      family. The human ALDH7 and -8 genes have a closer evolutionary relationship with
      the human ALDH3.

PMID- 9161418
TI  - Molecular characterization of a gene encoding a membrane protein of Spiroplasma
      citri.
AB  - A 9.6-kb genomic DNA segment, previously cloned from the phytopathogen
      Spiroplasma citri BR3-3X [Fletcher et al. (1981) Phytopathology 71, 1073-1080],
      contained several open reading frames including one encoding a 58-kDa protein. In
      this work, the transcription initiation site of the P58 mRNA was mapped and part
      of the gene was expressed in Escherichia coli as a fusion protein. A synthetic
      peptide, whose sequence is included in the fusion protein, was produced.
      Antibodies against both the fusion protein and the peptide reacted with a 60-kDa
      protein in a S. citri total protein extract. Hydrophobicity characteristics of
      this protein and its fractionation into the detergent phase indicated that P58,
      which shares limited sequence similarity with the adhesin of Mycoplasma hominis
      and the attachment protein of M. genitalium, is an integral membrane protein.

PMID- 9161419
TI  - Cloning of the p53 tumor suppressor gene from the Japanese medaka (Oryzias
      latipes) and evaluation of mutational hotspots in MNNG-exposed fish.
AB  - A full-length cDNA clone of the medaka (Oryzias latipes) p53 tumor suppressor
      gene was isolated from a cDNA library from adult liver tissue, sequenced and
      characterized. Sequence analysis revealed a high degree of homology between
      putative functional domains of medaka p53 and p53 genes from other vertebrate
      taxa including rainbow trout (Oncorhynchus mykiss), frog (Xenopus laevis),
      chicken (Gallus gallus), rat (Rattus norvegicus), mouse (Mus musculus), hamster
      (Mesocricetus auratus), green monkey (Ceropithecus aethiops) and human (Homo
      sapiens). A single 1.9-kb p53 mRNA is expressed at a very low level in normal
      adult liver tissue. This transcript is similar in size to transcripts of p53
      genes from other species. Preliminary screening of six MNNG-induced tumors in
      four adult medaka revealed no mutations within characteristic mutational hotspots
      encompassing conserved domains IV and V.

PMID- 9161420
TI  - Transcriptional analysis of the groESL operon of Neisseria gonorrhoeae.
AB  - The nucleotide sequence upstream of the groEL gene of Neisseria gonorrhoeae has
      been determined. Upstream of groEL is a homolog of groES and the divergently
      transcribed frpB gene. The promoter region of groES lacks the inverted repeat
      sequences (IR) that act as a regulatory element controlling the expression of
      similar operons in many other bacterial species. This region contains overlapping
      consensus sequences for sigma 32-dependent and sigma 70-dependent promoters, and
      an appropriately placed transcription start point was mapped downstream of these
      promoters. Northern hybridization demonstrated that synthesis of a full-length
      groES-groEL transcript was induced in heat-stressed cells. These experiments also
      revealed the presence of a shorter groES-specific transcript, apparently the
      result of the premature termination of transcription at an IR situated between
      the groES and groEL genes.

PMID- 9161421
TI  - A DP1 pseudogene derived from an aberrantly processed RNA.
AB  - A fragment of mouse genomic DNA containing a pseudogene corresponding to the
      processed transcript of the DP1 locus was isolated and analysed. The pseudogene
      sequence, on comparison with the genomic locus and the corresponding mRNA
      indicated the presence of several small deletions and point mutations. In
      addition, the pseudogene showed a deletion for the second exon of the DP1 gene
      indicating the occurrence of an exon slippage event during its formation. We also
      describe the chromosomal mapping of the pseudogene to chromosome 1 by
      fluorescence in situ hybridisation and distinguish it from the localisation of
      the actual murine DP1 genomic locus on mouse chromosome 8.

PMID- 9161422
TI  - Cloning and expression of squalene epoxidase from the pathogenic yeast Candida
      albicans.
AB  - The allylamine antimycotic terbinafine prevents the formation of sterols by
      specifically inhibiting squalene epoxidase (SE). The biological and biochemical
      action of terbinafine on fungal pathogens has been well investigated, but little
      is known at the molecular level. Here we report the cloning, sequencing and
      expression of the target of terbinafine from the major pathogen Candida albicans.
      A C. albicans genomic DNA library was constructed in gamma ZAP Express and
      screened with a DNA fragment obtained by polymerase chain reaction with two
      primers designed from sequences common to Saccharomyces cerevisiae and rodent
      SEs. Two types of clone, approximately 3.9 kbp and 4.1 kbp, were isolated. Both
      contained an identical open reading frame of 1488 nucleotides, while a few
      sequence differences were found in the flanking regions, suggesting an allelic
      heterogeneity. The deduced protein sequence of C. albicans SE, 496 amino acids
      (55324 Da), is 54% and 41% identical to those of S. cerevisiae and rat,
      respectively. A 1.8-kb transcript was observed on Northern blots of C. albicans
      mRNA. Polyclonal antibodies, raised against an internal peptide of C. albicans
      SE, recognized a protein associated with the particulate fraction of M(r) 55000
      on Western blots of C. albicans extracts. C. albicans SE was overexpressed in S.
      cerevisiae with the expression vector pYES2. In homogenates from S. cerevisiae
      overexpressing the C. albicans protein SE activity was 10-fold higher than the
      endogenous activity from controls.

PMID- 9161423
TI  - Characterization of the two H1(zero)-encoding genes from Xenopus laevis.
AB  - We have analyzed the promoter and the coding sequences of the two homologous
      histone H1(zero)-encoding genes from Xenopus laevis, here termed H1(zero)-1 and
      H1(zero)-2. Both genes encode proteins of 193 amino acids and differ at just 16
      amino-acid residues. Putative regulatory sequences identified in the promoter
      region are the same and are highly conserved. However, significant differences
      exist in the 5' untranslated regions (UTR) of the transcribed sequences of these
      two genes, such as several deletions in the 5'-UTR of the H1(zero)-2 gene in
      comparison with the H1(zero)-1 gene 5'-UTR. The 3'-UTR is a short sequence of
      about 200 bp which is unexpected compared with the long 3'-UTR of mammalian
      H1(zero) mRNA, but it is in the same size range as in avian H5 mRNA. Thus, the
      main differences between these two genes are observed in sequences potentially
      involved in the regulation of the H1(zero) gene expression such as the 5'-UTR.
      The two genes are expressed during embryogenesis and in several adult tissues. We
      discuss these findings in terms of the evolution of histone H1(zero) genes in
      vertebrates and the appearance of histone H5 in avian species.

PMID- 9161424
TI  - Isolation and characterisation of a linked cluster of genes from Agrobacterium
      tumefaciens encoding proteins involved in flagellar basal-body structure.
AB  - We report the DNA sequence of 7205 bp of the Agrobacterium tumefaciens
      chromosome. This contains a putative operon encoding homologues of the flagellar
      rod and associated proteins FlgBCG and FliE, the L and P ring proteins (FlgHI) a
      possible flagellum-specific export protein FliP, and two proteins of unknown
      function, FlgA and FliL. Several of these genes have overlapping stop and start
      codons. Three non-flagellate Tn5-induced mutations map to this operon: fla-11 to
      the first gene, encoding the rod protein FlgB; fla-15 to flgA; and fla-12 to
      fliL. A site-specific mutation introduced into the final gene in this cluster,
      fliP, also resulted in a non-flagellate phenotype. This indicates that the operon
      is expressed, and that at least FlgB, FlgA, FliL and FliP are required for
      flagellar assembly in A. tumefaciens. The bulk of this operon is conserved in the
      same order in Rhizobium meliloti.

PMID- 9161425
TI  - The Agrobacterium tumefaciens motor gene, motA, is in a linked cluster with the
      flagellar switch protein genes, fliG, fliM and fliN.
AB  - We report the sequence of 3978 bp of the Agrobacterium tumefaciens chromosome
      which contains a putative operon encoding the homologues of the transmembrane
      proton channel protein MotA, and the flagellar switch proteins FliM, FliN and
      FliG. Two transposon insertions in fliG result in a non-flagellate phenotype,
      indicating that this gene at least is required for flagellar assembly.

PMID- 9161426
TI  - The ovine SOX2 gene: sequence, chromosomal localization and gonadal expression.
AB  - The SOX gene family consists of a large number of embryonically expressed genes
      capable of encoding putative transcription factors and related by a DNA-binding
      domain, the HMG-box. We cloned and characterized the ovine SOX2 transcript using
      the screening of a testis (12dpp) cDNA library with a probe containing the SRY
      HMG-box and we performed 3'RACE experiments. The ovine SOX2 sequence is strongly
      conserved in comparison to the human, mouse and chicken homologues and is located
      on sheep chromosome 1q33. The SOX2 expression pattern in developing gonads is
      consistent with the hypothesis that this gene plays a role in the germ cell line.

PMID- 9161427
TI  - [Surveillance of treated gynecological cancers].

PMID- 9161428
TI  - [Assay of lactic acid in the cerebrospinal fluid for the diagnosis of bacterial
      meningitis. Strategies for the choice of discriminatory threshold].
AB  - OBJECTIVES: In search for a supplementary marker of bacterial meningitis in cases
      where conventional bacteriology, cytology and chemistry are insufficiently
      contributive to diagnosis, we assessed the value of cerebrospinal fluid lactate
      levels in children with bacterial meningitis. PATIENTS AND METHODS: Cerebrospinal
      fluid lactate levels were measured from all spinal taps performed in a pediatric
      emergency care unit over a two-year period. Of the 332 usable samples there were
      32 cases of bacterial meningitis, 104 cases of viral meningitis and 196 other
      diagnoses (non meningitis). RESULTS: Average lactate concentration 7 +/- 4 mmol/l
      in bacterial meningitis versus 2.1 +/- 0.6 mmol/l in viral meningitis (p <
      0.0001). The value of lactic acid concentrations in discriminating between
      bacterial and viral meningitis was found to be superior to that of other
      chemistry results: protein, glucose, chloride. The discriminatory threshold of
      cerebrospinal fluid lactate was 3.7 mmol/l with sensitivity of 80% and a
      specificity of 98%. CONCLUSION: We propose routine assay of cerebrospinal fluid
      lactate in all cases of suspected meningitis.

PMID- 9161429
TI  - [Acidosis and hyperlactatemia in acute sodium valproate poisoning].
AB  - OBJECTIVES: We searched for signs of metabolic acidosis and associated
      hyperlactatemia in case of sodium valproate overdose. PATIENTS AND METHODS: A
      retrospective study was conducted in the toxicology intensive care unit at the
      Fernand Widal hospital from 1990 to 1995. Patients retained for study had sodium
      valproate levels above the therapeutic range (> 600 mumol/l). Data collected
      included past history, intubation for mechanical ventilation, administration of
      catecholamines and infusion of bicarbonate or sodium lactate, and blood pressure.
      Laboratory tests included serum sodium valproate, pH, PCO2, bicarbonate, anion
      balance and lactate. RESULTS: The study included 22 consecutive patients. None
      had a history of liver disease. Thirteen patients were intubated before admission
      to intensive care. Two received catecholamines. None of the patients received
      bicarbonate or sodium lactate. Mean blood pressure was 118 +/- 16 mmHg, mean
      serum sodium valproate was 2668 +/- 2437 mumol/l, mean pH was 7.41 +/- 0.08, mean
      PO2 35.6 +/- 8.0, mean anion imbalance 23.2 +/- 6.0 mmol/l and mean lactate 5.0
      +/- 2.1 mmol/l. There was a significant correlation between lactase and pH (p <
      0.003). CONCLUSION: We found metabolic acidosis with major anion imbalance and
      high lactate levels in patients with acute sodium valproate intoxication.
      Hyperlactatemia could be due to the direct effect of sodium valproate or to an
      unknown mechanism.

PMID- 9161430
TI  - [Giant buccal aphthosis caused by nicorandil].

PMID- 9161431
TI  - [Homeless persons and hospital emergencies in a UHC in Paris].

PMID- 9161432
TI  - [Anaphylactic shock related to the treatment of malaria with halofantrine].

PMID- 9161433
TI  - [Viral load].

PMID- 9161434
TI  - [Myocardial infarction in the elderly. How to improve prognosis?].

PMID- 9161435
TI  - [Specific immunotherapy of respiratory allergies].

PMID- 9161436
TI  - [Porphyria cutanea tarda: relations to the hepatitis C virus].

PMID- 9161437
TI  - [Fluoroquinolones. Pharmacokinetic properties and new pharmacodynamic concepts].

PMID- 9161438
TI  - [Dermoid cyst of the ovary].

PMID- 9161439
TI  - [Hydatid cyst of the liver].

PMID- 9161440
TI  - [Past and present status in the design of infant formulas].
AB  - This paper describes briefly the history of infant foods, from the alternate ways
      of feeding developed during the late 19th century to the present-day infant
      formulas, and enumerates the different available types (milk-based, soy-based,
      hypoallergenic, lactose-free, etc,). Among the nutritional aspects the main
      characteristics of formulation are emphasized, especially within the nitrogen,
      fat and mineral fractions. Considering the nitrogen fraction, it must be taken
      into account that the amino acid profiles in milk-based formulas differ according
      to the casein/whey proteins ratio (either 80:20 or 40:60 in the so-called
      "adapted" or "humanized"). On the other hand, it has been recognized recently
      that some non-protein components of human milk, such as taurine, carnitine and
      nucleotides, are relevant to infant nutrition and therefore, they are being
      included in some formulas. Regarding fat, essential fatty acids supply is very
      important; present recommendations stress the importance of providing n-6 to n-3
      series ratios close to that found in human milk and also a preformed supply of
      long-chain polyunsaturated fatty acids. Among minerals, bioavailability and
      relative proportions of trace elements are important issues in formulation. Other
      concepts of relevance are the renal solute load and the osmolarity because of
      their effect on neonate's metabolism.

PMID- 9161441
TI  - [Development of a computer program to assess nutritional status of infants and
      preschool children].
AB  - A computer program named INFANDIET has been designed with a Window's application
      (ToolBook software vs. 1.53), based upon object-oriented programming, and devised
      to assess the nutritional status of infants by using compatible computers PC.
      Additionally, it is a useful tool to elaborate personalized diets. This program
      has been developed to assist health professionals and students in the evaluation
      of the infant nutritional status by a) creating and managing clinical histories
      with anthropometrical, immunological and clinical data; b) showing infant dietary
      guidelines, with the ability to update the nutritional and food composition
      database of the program; c) giving information about infant nutrition; d) and
      presenting a complete list of references.

PMID- 9161442
TI  - [Brachial indicators of fat and muscle in schoolchildren of a rural community
      according to social groups (General Lavalle, Buenos Aires, Argentina)].
AB  - In order to determinate the body composition in a schoolchildren rural community-
      General Lavalle, Buenos Aires, Argentina--the arm circumference (AC) and the
      triceps skinfold (TS) growth were studied by cross-sectionally methods. From
      those measurements the arm muscle area was calculated. All the data were
      transformed to "Z" scores. The sample was divided into seven social groups
      according to the educational and occupational levels of parents. Statistics
      analysis of variance (ANOVA test) and Tukey test were performed. Statistically
      significant differences in AC an TS among the social groups were observed (p <
      0.001). Two different patterns of brachial composition were observed according to
      the social group. This composition was different with respect to urban
      populations. Our findings suggest an environmental adaptation by growth.

PMID- 9161443
TI  - Changes of serum lipids in vitamin K3 (menadione) treated rats.
AB  - The effect of high doses of vitamin K3 (10 to 50 mg/kg/day of menadione,
      administered intramuscularly) on the serum content of total lipids, cholesterol,
      phospholipids and triglycerides in male Wistar rats was evaluated. This
      experimental group was compared with another group that received intramuscular
      injections of 10 to 50 mg/kg/day of sodium bisulphite. Hypervitaminosis K3 was
      diagnosed by jaundice (due mainly to unconjugated bilirrubin) and by anemia which
      was particularly evident at doses of 40 and 50 mg/kg/day of menadione. These
      doses of menadione increased serum content of total lipids, phospholipids, and
      triglycerides but decreased cholesterol. The results show that overdoses of
      vitamin K3 alter lipid metabolism. The influence o participation of liver damage,
      fastening, as well as various endocrine and hematological changes are considered
      responsible for the alterations in serum lipids.

PMID- 9161444
TI  - [Influence of intake of vegetable oils on the in vitro intestinal absorption of
      glucose in golden hamsters].
AB  - Male Hamsters (Mesocricetus aureatus) were fed standardized diets with 15% Rose
      hip, Sunflower, Olive or Coconut oil for four weeks, in order to determine the
      influence of vegetable oils with different degree of unsaturation over the
      intestinal absorption of glucose. The concentration of glucose in the serosal
      solution at 20, 40 and 60 minutes, was quantified in pieces of everted intestine
      of each animal, after the feeding period was over. A lower concentration of
      glucose was observed in the Olive group, although it was statistically
      significant only when compared to the Rose hip and Coconut oil group (P < 0.05).
      The groups fed Rose hip and Coconut showed a similar pattern, even though they
      are oils with extreme and opposing degree of unsaturation. We explain this by the
      triggering of homeostatic mechanisms in the cellular membranes of the enterocytes
      when faced to a nutritional stress caused by the saturated and unsaturated fatty
      acids of those oils. We can conclude that the in vitro intestinal absorption of
      glucose in golden hamster is modified by dietary lipids. The lower absorption of
      glucose seen in the Olive group could be caused a specific action of a fatty acid
      or of its degree of unsaturation.

PMID- 9161445
TI  - Polyunsaturated fatty acid deficiencies: effects on hepatic plasma membrane fatty
      acid composition and enzyme activity.
AB  - Research on dietary polyunsaturated fatty acids (PUFA), on the activity of
      5'nucleotidase and adenylate cyclase are largely contradictory due, mostly, to
      the absence of adequate control group. In this study; four different diets have
      been evaluated on the 5'nucleotidase and adenylate cyclase activities in rat
      liver plasma membranes. Wistar rats were given a semisynthetic diet in which
      lipids were supplied by 5% of either peanut oil (n-3 PUFA deficient diet), cod
      liver oil (n-6 PUFA deficient diet) partially hydrogenated palm oil (total PUFA
      deficient diet) and a mixture of peanut and rapeseed oil (control group). Liver
      plasma membranes were separated by using a Percoll gradient in a Beckman JA 20
      centrifuge. 5'nucleotidase and adenylate cyclase activities were measured in a
      liquid scintilation detector by following the degradation of 3HAMP (adenosine
      monophosphate) and production of 3HcAMP (cyclic adenosine monophosphate)
      respectively. Animals fed the total PUFA deficient diet exhibited significant
      lower body weight and lower liver weight than did the control group. Low
      cholesterol concentrations were observed in animals deficient either in n-3 or
      total PUFA in relation to the control group. All dietary deficiencies studies
      provoked reduced phospholipid levels. Phosphatidylcholine and
      phosphatidylethanolamine were not modified whatever the deficiency studied.
      Phospholipids fatty acid composition was significantly modified by the diets
      studied. The specific activity of 5'nucleotidase in hepatic plasma membrane was
      independent of dietary PUFA. The catalytic unit of adenylate cyclase complex in
      totally deficient animals was augmented. The unit of the enzyme stimulated by the
      guanydyl imidodiphosphate (GppNHp) in n-3 PUFA deficient animals was augmented
      and reduced in animals receiving the n-6 PUFA deficient diet. In conclusion, our
      results show that each dietary PUFA deficiency modifies differently the
      proportions of phospholipid classes and their fatty acid composition. The
      mechanisms responsible for these modification remain to be elucidated. However,
      the phospholipid fatty acid changes did not influence the 5'nucleotidase activity
      except in the case of extreme excess which concerns more toxicology than
      nutritional modifications. Finally, the catalytic unit (Forskoline + GDP beta s)
      of adenylate cyclase complex and the regulatory unit (GppNHp) may be sensitive to
      alterations in PUFA composition.

PMID- 9161446
TI  - [Interaction of vitamin A and zinc in lactating rats. Experimental deficiency
      model].
AB  - An experimental deficiency model of vitamin A and zinc in lactating rats was
      developed. The experimental design consisted in a depletion period of 4 weeks
      immediately after birth where test group animal received a casein based feed,
      deficient in zinc and vitamin A, and a control feed according to the
      recommendations of the Committee on Laboratory Animal Diets. Female Rathus
      norvergicus, var albinus (Rodentia, Mammalia) with 6 young males each were used.
      These came from the Bioterio of the Faculdade de Ciencias, Farmaceuticas of USP.
      At the end of the depletion period it was found that the weight of the males
      control group (109.1 g +/- 3.9 g) was significantly greater than that of the test
      group (40.8 g +/- 6.7 g). The same was true for the concentration of zinc in the
      femurs of these animals, in the control group the concentration was significantly
      greater (115.7 micrograms/g +/- 5.4 micrograms/g) than in the test group (35.5
      micrograms/g +/- 3.3 micrograms). The concentration of vitamin A in the plasma of
      the control group (31.5 micrograms/dL +/- 2.5 micrograms/dL) also was
      significantly greater than the test group animals (8.9 micrograms/dL +/- 3.4
      micrograms/dL). The concentration of hepatic vitamin A was similar for both
      groups. We can conclude that there was interaction of zinc and vitamin A, by
      liver and depletion in zinc. Although the plasmatic concentration of vitamin A
      indicates a depletion, this cannot be considered as total because of the hepatic
      reserves.

PMID- 9161447
TI  - Extraction, purification and some partial characterization of alpha-amylase
      inhibitors from wheat Iapar 28-Igapo.
AB  - alpha-Amylase inhibitors from wheat (Triticum aestivum) cultivar Iapar 28-Igapo
      were extracted with water in a 1:10 (w:v) ratio and precipitated with ammonium
      sulfate between 20-50% saturation, followed by DEAE and CM-cellulose
      chromatography. One inhibitor was purified and designated as CMC-IB, and had
      electrophoretic mobilities of 0.23 and 0.54 in alkaline and acidic conditions,
      respectively. This inhibitor was 750 times more active on human salivary alpha
      amylase (HSSA) than porcine pancreatic o-amylase (PPA). The preincubation time
      required for maximum complexation with HSA was 20 minutes and optimum pH of
      inhibition was 7.5. The inhibitor CMC-IB was stable at 0 degrees C and maintained
      50% of inhibitory activity against HSA, when incubated at 98 degrees C for one
      hour.

PMID- 9161448
TI  - [Proteolytic activity control in fish silage].
AB  - Microbial fish silage was produced from ground low commercial fish species added
      with 15% mollase and stored at 35 degrees C. Experiment were conducted to
      evaluate the effect of the addition of a commercial preparation of bromeline
      (0.20-0.90%) to the fish silage. Liquefaction was evaluated measuring both the
      product consistency and its non protein nitrogen content. Results indicate that
      bromeline addition (0.7 or higher), increases dramatically the rate of
      proteolysis and decreases the time required for liquefaction from 15 days (no
      enzyme control) to only 12 hours. Therefore, the use of the commercial
      preparation of bromeline is highly recommended for silage production.

PMID- 9161449
TI  - [The use of deffated corn germ in flour manufactured to bakery products].
AB  - The flour of deffated corn germ is a by-product of the corn industry milling
      dried which is actually subutilized in human consumption. In this study, two
      samples of corn deffated germ of different particle size were physicochemically
      characterized: fine fraction (FF) and medium fraction (FM) and they were added to
      wheat flours to obtain composite flours with substitution levels of 5- 10- 12-
      15% mixtures. These mixtures were used to manufacture sandwich bread in bakeries,
      which were physico-chemically and sensorially analyzed. (FF) and (FM) were found
      to provide from 20 to 35% of dietary fiber. From the manufactured bread loaves,
      the ones containing 10% of (FM) and 10% of (FF) were selected because they did
      not differ in specific weight, color, flavor and texture at a 95% confiability
      from those elaborated with 100% wheat flour. In the acceptability test given to
      200 consumers, it was found that bread with 10% FF substitution was more widely
      accepted (48%) than that containing 100% wheat flour; and that of 10% of (FM) had
      the same level of acceptability (28%) as the control bread. It can be concluded
      that the deffated corn kernel represents a raw material available in this country
      that could be used in bread elaboration as a partial replacement for imported
      wheat.

PMID- 9161450
TI  - [Development of an intermediate moisture product for the elderly based on
      texturized soybeans].
AB  - In accordance with the fact the aging process is closely related to the
      individual nutrition, it is possible to infer that the daily diet could help and
      improve, to a certain degree, to the elderly well-being. Based on this and making
      use of the food technology expertise, the development of a low cost, easily
      prepared and preserved product, in accordance with the taste and needs of the
      elderly people was considered. The objective of this project was to elaborate an
      intermediate moisture food (IMF) based on texturized soy protein with carrots,
      potatoes and peas, adding humectants and microstatic agents according to the
      moist and dry infusion methods. Fried bacon was added to some formulas in order
      to evaluate the sensorial preference of the product with and without bacon by
      elderly people and effect of the bacon on the water activity (aw) reduction. The
      aw for the product with added bacon was 0.859 and 0.896 for the one with no added
      bacon. The product with added bacon allowed 20% of the nutritional requirements
      of the elderly people of protein, vitamin A and thiamine. Both formulas were
      equally highly accepted by the elderly people (80%) and were microbiologically
      stable for 8 weeks period at 25 degrees C and 55% RH in
      aluminium/cellophane/polyethylene and polyester/polyethylene flexible packages.
      We can conclude that IMF may be an alternative to improve the diet of the elderly
      people.

PMID- 9161451
TI  - Carotenoid composition and vitamin A value of Brazilian loquat (Eriobotrya
      japonica Lindl.).
AB  - Six sample lots of loquat commercialized in Campinas, Brazil were analyzed for
      their carotenoid composition beta-carotene (7.8 micrograms/g), zeta-carotene (0.1
      micrograms/g), neurosporene (1.1 micrograms/g), beta-cryptoxanthin (4.8
      micrograms/g), 5,6-monoepoxy-beta-cryptoxanthin (0.6 micrograms/g), violaxanthin
      (1.6 micrograms/g), (0.8 micrograms/g) and auroxanthin (0.9 micrograms/g) were
      identified beta-Carotene and beta-cryptoxanthin were the principal pigments,
      being responsible for 44% and 27%, respectively, of the total carotenoid content
      (17.6 micrograms/g). Both were also the principal contributors to the vitamin A
      value of 175 RE/100g. The carotenoid composition of the Brazilian loquat
      resembles that of the Japanese loquat variety Tanaka.

PMID- 9161452
TI  - [Probiotics and their future].
AB  - This review examines recent scientific information about probiotics, their
      microbiological composition, general characteristics, function and methods of
      action as well as factor which determine their activity. The principal producers
      of probiotics and their future in human and animal nutrition are also discussed.

PMID- 9161453
TI  - [Influence of physical activity upon bone mineralization of school age children
      of both sexes].
AB  - Obtention of an optimal peak bone mass decreases the risk of osteoporosis in
      adult life. An increase of physical activity favors bone mineralization in
      adults. However, in teenagers sports that could delay puberty can delay bone
      mineralization, while sports with a normal caloric intake favor mineralization.
      The objective of this study was to evaluate the effect of intensity of physical
      activity and the type of sport, upon bone mineralization before and during
      puberty. A sample of 144 normal school age children of both sexes aged 7 to 14
      years, practicing various degrees of physical activity, was selected. Bone
      mineral density (BMD) of whole body, spine and hip was measured with a dual
      photon absorptiometry densitometer and compared with values of normal school
      children of similar ages. A better adequation of BMD of whole body and spine in
      school age children with increased physical activity was detected. Prepuberal
      female gymnasts had decreased BMD of whole body. Puberal school age children with
      decrease physical activity had diminished BMD. These results led us conclude that
      physical activity favors bone mineralization in spine and hip, specially during
      puberty.

PMID- 9161454
TI  - [Breast-feeding during the first month of life in Cordoba city, Argentina].
AB  - In the foregoing investigation breast-feeding during the first 30 days of life
      was studied in a representative sample of 620 babies born and settled down in the
      city of Cordoba Argentina. To analyse this information, the classification of
      breastfeeding suggested by the WHO/UNICEF was used. The results reveal that being
      a month old, 26% of the babies had complete breastfeeding 60% had partial
      breastfeeding and the remaining 14% did not have it at all. Among the children
      with complete breast-feeding, 21% was exclusive and 5% was prevailing. 18% of the
      babies were exposed to breastfeeding before an hour and a half after they were
      born, the average number of nursings a day was 7.3 (D.S. 1.9) taking less than 15
      minutes to reach the 57%; and with a free-demanding timetable in 44%. The
      children with partial breast-feeding were classified into low, medium, and high
      being 20%, 54%, 22% respectively. The average age in which another milk was
      introduced was 3.7 days, and the main reasons were "insufficient mother milk",
      and "the child's hunger". Among the children with artificial lactation, 87% were
      once exposed to breastfeeding, the weaning took place during the 4 days in
      average (D.S. 5.6) and in an abrupt way in 55% of them. The Health personnel
      helped supporting the introduction of lacteal formula in 68% of the children with
      partial lactation and in 42% of the cases of complete abandon of natural
      breastfeeding.

PMID- 9161455
TI  - [Dietary pattern and nutrient intake in preschool children from three rural
      villages in the Province of Santa Rosa, Guatemala].
AB  - We present here the results of a nutritional survey to show the pattern of food
      consumption, as well as nutrient intake, of 303 pre-school children (six to 71
      months old) from three rural hamlets of the South-East region of Guatemala. This
      survey was performed prior to the establishment of a nutritional intervention in
      the same geographical area. Information was gathered from June through August
      1991, by personnel from the Center for Studies of Sensory Impairment, Aging, and
      Metabolism (CeSSIAM) using two data collection instruments during home visits.
      Informats were mothers or other caretakers in charge of the children feeding.
      Data collected were initially converted to individual food item weight, and then,
      to micronutrients values. These values were used to establish their adequacy to
      standard requirements for children of these ages. Results showed a pattern in
      which corn tortilla, and beans were the most commonly consumed food items. Those
      items were also the relatively most important sources of calories, protein, and
      iron. Vitamin A intake was low, and it came mainly from plant sources. Nutrients
      intake was below the recommended dietary allowances, except for protein and iron.

PMID- 9161456
TI  - [Atherogenic factors in the diet of the Costa Rican population, 1991].
AB  - The present study analyzes the aterogenic factors of the diet of the Costa Rican
      population in various population and geographic groups. Data utilized was
      obtained from the Second National Survey on Apparent Food Consumption, 1991.
      Results found that on the national level consumption of fats, in relation to
      total caloric intake was higher than recommended levels. Likewise, the percentage
      of saturated fats exceed the established recommendations for prevention
      cardiovascular disease, and the intake of polyunsaturated fats was inferior to
      recommended levels. P/S ratio was 0.3, a value within the range considered to be
      aterogenic. Cholesterol intake is considered to be adequate. Cholesterol
      Saturated-Index (CSI) of the majority of the diets studied was high, as reported
      in similar situation in other countries where cardiovascular disease is likewise
      the first cause of death. Dietary fiber was found to be in the lower levels of
      the daily recommendations. Also, the intake of vitamin C and E shows normal
      values, while intake of vitamin A is deficient. The principal source of three
      types of fat in the diet, as well as vitamin E, was shortening made from palm
      oil, which in spite of no being a rich source of unsaturated fatty acid, the
      consumption of it is high. Egg is the main source of cholesterol and dietary
      fiber is primarily obtained from beans. In conclusion, the Costa Rican diet
      presents a nutritional imbalance which can be considered an atherogenic risk
      factor for cardiovascular disease.

PMID- 9161457
TI  - Colon cancer in rats and diet in the Sonoran desert region of Mexico.
AB  - The role of dietary fiber in colon cancer is still not clear. Epidemiological
      studies suggest a protective role for high fiber intake. However the data suggest
      that the effects of fiber must be considered in the context of the total diet and
      its interactions with other dietary components. The typical Sonora diet is high
      in dietary fiber (7.8%) and the majority of this fiber (71%) is insoluble.
      Comparing the incidence of colon cancer in Sonora with its neighboring state of
      Arizona, in 1991, Sonora reported 40 cases of colon cancer, a population of
      1,823,606, compared to 1432 for Arizona (3,763,322 inhabitants). The typical
      regional diet was evaluated for its protective effect in the development of colon
      cancer in rats injected with azoxymethane, AOM. The regional diet showed a
      tendency to protect against colon cancer, an incidence of 45% compared to 66% for
      the control diet, although this effect was not significant (p = 0.15). Further
      studies are needed to fully evaluate the diet and certain interactive dietary
      factors such as fat, quantity as well as type, protein, calcium and antioxidant
      nutrients.

PMID- 9161458
TI  - [Changes in calcium, phosphate, magnesium and sodium content in bones of
      ovariectomized rats].
AB  - Bilateral ovariectomies (OVX) or sham surgeries-respectively-were performed in
      two lots of ten female Wistar rats, 90 days old. Food was available ad libitum to
      sham rats, and it was restricted to OVX ones. At 15, 30, 45 and 90 days, a
      segment of their tails was sectioned. At 180 days all rats were sacrificed and
      the left femurs were excised. With the tail's bones and the femurs we determined
      Ca++, PO4(-3), Mg++ y Na+ concentration. After 15 days, no significant
      differences inter lots were observed (p < 0.05) in all ions contents. After 30
      days Ca++ value was significantly less (p < 0.05) in the OVX rats than in the
      sham ones. After 45 days all the analyzed OVX rats ions were significantly less
      (p < 0.05) than the sham values. That difference inter lots was greater after 90
      days. Finally, day 180th gave a decrease in the OVX rat values-from the femur-as
      follows: for Ca++ 31%, for PO4(-3) 29%, for Mg++ 31.6% and for Na+ 29%. Our
      results shown that in 90 days old ovariectomized rats, the concentration of
      calcium, phosphate, magnesium and sodium in the tail bones is a good indicator of
      bone mass loss, after 45 days of ovariectomy.

PMID- 9161459
TI  - [Chilean edible sea macroalgae as sources of dietary fiber: effect on apparent
      digestibility of protein, fiber, and energy and fecal weight of rats].
AB  - The inclusion of algae as a source of fiber in the diet is justified by the
      present need to increase the intake of this nutrient. The aim of this study was
      to study on rats, the effect of dietary algae fiber on fecal weight and apparent
      digestibility of energy, protein and fiber. The type of algae studied were
      cochayuyo (frond) and ulte (basal part) (Durvillea antarctica), luche verde (Ulva
      lactuca) and luche rojo (Porphyra columbina). All these algae were boiled and
      dried at 55 degrees under air flow. Male rats, Wistar strain of 25 days of age,
      were fed during 29 days with diets containing casein plus the inclusion of 10%
      (weight) of one of these algae dietary fiber. A group having no fiber intake was
      used as a Control group. Algae content of dietary fiber ranged between 58.2-75.6
      g/100 g (dry weight), soluble fiber portion constituted 37.9-52.4%. In relation
      to the Control group it was found significant reduction in the apparent
      digestibility of protein and energy, and a significant reduction in fecal weight.
      Dietary fiber digestibility ranged between 21.1 and 43.1%. This study shows that
      algae can be an excellent dietary fiber source, very useful to prevent or treat
      different fiber-deficiency related diseases.

PMID- 9161460
TI  - [Experiences during training of a group for tasting bovine meat at an industrial
      refrigerated abattoir in Venezuela].
AB  - During three months, a group of people (meat consumers and active personnel) of a
      Venezuelan packing house were asked to assign discretionary scores to a sample of
      103 beef longissimus steaks in order to familiarize them with the score sheet and
      to their future job as panelists. Scores assigned to 37 steaks by seven
      candidates that assisted regularly to these preliminary sessions (out of 12
      attendants), were subjected to Analysis of Variance (ANOVA) to determine
      variability among judges before training. The whole group (n = 12) potential
      candidates from both sexes, and ranging between 25 and 45 years, were interviewed
      and pre selected for formal training. Triangle tests were used as selection tool
      and allowed for dismissing two of them. Training reinforced acquaintance with
      test procedures and improved natural abilities, sensitivity and memory for test
      attributes by using an 8-point descriptive scale to describe samples differing in
      fiber tenderness, amount of connective tissue, overall tenderness, juiciness, and
      flavor intensity. After 2 mo. of training (5 h weekly) the first panel
      performance evaluation (PPE) was conducted over 4 days with 3 sessions per day
      and 3 samples per session with 9 different samples. Data for each candidate were
      subjected to one-way ANOVA and F-ratio served as criteria to rank candidates'
      ability for describing each attribute. Panelist 7 and 8 rated last and were
      excused to conform an 8-member panel. The panel evaluated 300 samples during a 6
      mo period and a second PPE was conducted. The second PPE revealed changes in
      relative ranking positions. Data from the first 40 (out of 300) samples were
      subjected to ANOVA for testing score (panelist) variability after training. A
      significant effect of panelist was detected before (P < .05) and after (P < .001)
      training, but a much greater variability became apparent in untrained candidates.
      Mean separation for trained panelist only differed in decimal units within the
      same points or adjacent points of the scale. Results validated methodologies used
      for panel training and the panel capability for sensorial evaluation of non
      processed beef.

PMID- 9161461
TI  - [Color loss evaluation of a dietary formulation in function of temperature,
      storage time and packaging].
AB  - Color loss of a dietetic formulae based on pumpkin (Cucurbita maxima), rice, hen
      and vegetable oils was evaluated. The product was under an accelerated test at
      temperatures of 40, 50 and 70 degrees C for a month. The kinetic reaction of
      color loss (quality loss indicator) was obtained with n = 1 and Ea = 11.5
      Kcal/mol. The product was also stored for sixth months at temperatures of 25, 30,
      35 and 40 degrees C using glass containers, laminated and composite cans (non
      metallic). The color was measured by a colorimetric method and by sensory
      evaluation under the defined conditions of time, temperature and package. The
      statistical analyses of the color loss measured by instrument was performed by a
      randomized block design with a significance level of p < 0.05. The results
      obtained both by the instrument and by the sensory evaluation method, showed that
      the temperature and storage time has significant effect (p < 0.05) on the other
      hand, the package does not have a significant effect. It was concluded from this
      study that the product could be stored for 6 months at temperatures below 35
      degrees C without changes in color.

PMID- 9161462
TI  - [Physical, chemical and microbiological quality of concentrated orange juices
      made in Venezuela].
AB  - Concentrated fruit juices are a very attractive type of product because of the
      many advantages they offer for reductions in packing, transportation and storage
      costs, and in addition, they offer the possibility of consumption outside
      harvesting time. Due to their potential in the international market, it is
      necessary to evaluate if they are accomplishing the quality requirements, and to
      know the different factors that can affect their stability. For this purpose,
      samples of national products were analyzed for physical, chemical and
      microbiological characteristics; the diacetyl test was performed as a measure of
      the sanitary conditions under processing. The samples analyzed comply with the
      national standards established by the Comision Venezolana de Normas Industriales
      (COVENIN N(o) 2395-86 Concentrados de frutas para consumo directo). It is
      advisable to determine the zero tolerant yeasts population because this type of
      microorganisms are responsible for spoilage whenever cold storage is interrupted,
      and because they can not be detected by the official procedures used to detect
      yeasts.

PMID- 9161463
TI  - [Effect of the light-dark cycle over the growth of male rats with different
      health status].
AB  - The light-dark cycle exerts an influence over the lipostatic mechanism in the
      superior vertebrate animals promoting an acceleration in the lipid synthesis rate
      during the dark period (in the case of rodents) and a higher lipolitic rate
      during the day. This cycle, the feeding habits, and the awake-sleep cycle are
      syncronized. The Growth Hormone is a molecule that facilitates the lipolysis and
      the protein synthesis. This hormone is released, by the pituitary gland, during
      the puberty and during the short wave sleep period. Modifying the light-dark
      cycle and in consequence the sleep-awake cycle and the food consumption, we
      pretend to study its influence over the growth rate in weight and length in
      animals that consume 100% of its nutritional requirements. Also want to
      dilucidate if an alteration of the cycle (18 h light 6 h dark) in the
      malnourished animals can revert the deficiency of the growth rate expected in
      these animals. Male Wistar rats (160); 21 days old, adapted to the temperature
      and to the light-dark cycle (12 h-12 h) during a week. Then, four groups were
      formed; Group I: Well nourished rats with a light-dark (12 h-12 h) cycle; Group
      II: Well nourished rats with a light-dark (18 h-6 h) cycle; Group III:
      Malnourished rats with a light-dark (12 h-12 h) cycle; Group IV: Malnourished
      rats with a light-dark (18 h-6 h) cycle. Its length and weight were registered
      weekly, obtained its growth rates, and the results were analysed by the ONE-WAY
      ANOVA and orthogonal contrasts. It was found a significant difference in the
      growth rate in weight between the Groups I and II; the growth rate in weight in
      the Group III had a higher slope than the rate in the Group IV but we did not
      find a significant difference. The growth rate in length did not show a
      significant difference between the Groups III and IV. The last weight in the
      malnourished animals represented 55% of the control animals last weight; and 47%
      of the Group IV. The last length of the animals of the Group III represented 90%
      of the control value, and the last length in the Group IV represented 82% of the
      control animals value. The feeding habits are modified changing the cycle to 18 h
      light and 6 h dark. Modifying the light-dark cycle appears an accelerating rate
      in the growth rate in weight in the well nourished animals, but not in the
      malnourished ones.

PMID- 9161464
TI  - Brewery waste as a substitute for soy protein in soy-brewer's yeast mixtures to
      feed broiler chickens.
AB  - We examined the replacement of soy isolated protein by a solid fraction coming
      from brewery liquid waste, in the preparation of soy protein and brewer's yeast
      mixtures (50:50) to feed growing chickens. The replacement of 20 percent soy
      protein by brewery waste protein to the diet, showed no significant differences
      in the growth and food intake of the chickens, when compared with soy protein fed
      chickens. Protein Efficiency Ratio (PER) and Net Protein Ratio (NPR) values of
      the diets were also very similar and the concentration of plasma and liver lipids
      remained approximately the same. Higher levels of brewery waste reduced the
      performance of chickens although total lipids, cholesterol and triacylglycerols
      in plasma, as well as total lipids and cholesterol in liver were not affected.
      The data reported here indicated that brewery waste can be used as a
      complementary protein source in broiler chicken diets.

PMID- 9161465
TI  - Effect of the type of dietary fat on cholesterolemia in rabbits fed brewer's
      yeast.
AB  - To determine the effects of the kind of dietary fat on cholesterolemia in rabbits
      fed with brewer's yeast, diets based on soybean protein isolate or on a mixture
      of soybean protein isolate and brewer's yeast (1:1) were used. They were combined
      with corn oil and coconut oil in four balanced, cholesterol-free diets. Twenty
      four rabbits were fed with 79 grams of diet per day during 3 weeks. After 14
      hours of fasting on the 22nd day, blood samples from the marginal ear vein were
      collected, animals were sacrificed and their livers dissected. There were no
      significant differences in the final plasma concentrations of the total lipids,
      triglycerides, total cholesterol, high density lipoprotein-cholesterol, and (low
      density lipoprotein + very low density lipoprotein)-cholesterol, even though
      groups fed yeast presented the highest values. Liver lipids were not affected by
      dietary treatment. However, when comparing the final plasma cholesterol with the
      initial cholesterol, a significant increase in the groups which consumed yeast
      with com oil (48 mg/dL) and coconut oil (91 mg/dL) was observed in comparison
      with the groups which only consumed soybean protein with corn oil (21 mg/dL) and
      coconut oil (36 mg/dL). The two-way variance analysis of these data showed that
      there was no fat-protein interaction and the hypercholesterolemic effects
      observed were associated with brewer's yeast consumption.

PMID- 9161466
TI  - [Fatty acid composition and cholesterol content in naturally canned jurel,
      sardine, salmon, and tuna].
AB  - To obtain more information about fatty acid profile and cholesterol content of
      fat extracted from canned fish in brine habitually consumed in Chile, four
      different species Jurel (Trachurus murphyi), Sardine (Sardinops sagax), Salmon
      (Oncorhynchus kisutch) and Tuna (Thunnus alalunga) were analyzed. The GLC of
      fatty acid methyl esters showed that the main group of fatty acids belongs to
      polyunsaturated, being omega-3 family the more important. The principal
      representants were eicosapentaenoic (EPA) and docosahexaenoic acids (DHA), with
      percentages between 5%-11% and 12%-22% respectively. Omega-6 family was
      represented mainly by arachidonic acid (AA) with percentages between 2%-4%.
      Cholesterol content was similar to the values found in other animal origen meats.
      The figures were between 41-86 mg of cholesterol per 100 g of edible product,
      Tuna in brine, was the product with the lowest content of cholesterol. The
      calculated amount of EPA, DHA and total omega-3 fatty acids indicated values
      between 95-604, 390-1163 and 609-2775 mg respectively per 100 g of edible
      product. Due these results is important to emphasize the consumption of this type
      of canned fish in brine, that they really represent a good dietary source of
      mainly polyunsaturated omega-3 fatty acids. The international recommendations
      indicate to increase the consumption of fish, due the beneficial effects
      described in relation with cardiovascular disease, which is the mean cause of
      death in Chile, country with a wide variety of marine origen foods, but with a
      contradictory answer about its consumption which is not incorporated in the
      current diet.

PMID- 9161467
TI  - Immunity aging. I. The chronic perduration of the thymus acute involution at
      puberty? Or the participation of the lymphoid organs and cells in fatal
      physiologic decline?
AB  - The author has focused the subject on the perduration of puberty thymus
      involution as a cause of immunity aging, a term in which he does not include
      senescence. The decrease between immune reactions against HIV1 at 25 years of age
      and those at 35 is considerable; the decrease is also indirectly revealed by
      spontaneous tumor exponentially growing incidence after 40 years in man and its
      equivalent, 16 months in mice: the immunity parameters indicate a regression
      correlated with this incidence growth. He regrets the neglect of suppressor cell
      and anti-idiotype problems by the basic immunologic research. Given the role of
      cofactors non specifically related to the antigen, such as that CD28 and its
      ligands, he suggests the interest to approach immunology via the science of chaos
      and fractals, which would be more appropriate than classical methodology to study
      highly complex phenomena on which apparently minimal interventions may induce
      considerable effects.

PMID- 9161468
TI  - Upregulation of enzymatic activity by interleukin-1 in osteoarthritis.
AB  - Osteoarthritis is a slow progressive disease characterized by destruction of the
      articular cartilage. The degradation of extracellular matrix components is mainly
      mediated by a family of enzymes, the metalloproteinases (MMPs), which are active
      at neutral pH. Interleukin-1 (IL-1) is a small peptide, active in autocrine and
      paracrine fashions. In vitro IL-1 increases the production of MMPs and inhibits
      the synthesis of collagen type II and proteoglycans. Its role in osteoarthritis
      is based on several findings: IL-1 is detectable in the synovial fluid and in the
      cartilage matrix of osteoarthritic joints; in vivo its deleterious actions can be
      reproduced by intra-articular injection of recombinant IL-1; biochemical changes
      observed in the cartilage matrix from osteoarthritic joints resemble those
      induced in vitro by IL-1; finally, antagonists of IL-1 are capable in vivo of
      preventing or at least diminishing the degradation of cartilage matrix components
      in several models of experimental arthritis. Interleukin-1 appears to be a main
      factor mediating cartilage matrix destruction. However, its role in human
      osteoarthritis, although highly probable, remains to be determined.

PMID- 9161469
TI  - Risk of diarrhoea, Clostridium difficile and cefotaxime in the elderly.
AB  - Clostridium difficile diarrhoea is an increasingly important nosocomial
      infection. Clostridium difficile infection is associated with antibiotic use. The
      elderly are at greatest risk. We reported an outbreak associated with the use of
      cefotaxime, a third-generation cephalosporin. We review the extent of this
      association, putative causal mechanisms and suggest an integrated approach to the
      control of C difficile infection which focuses on both limiting environmental
      contamination and reducing patient susceptibility. Future developments are also
      considered, especially the potential for vaccination.

PMID- 9161470
TI  - Blood pressure and dementia in the elderly: epidemiologic perspectives.
AB  - High blood pressure is associated with an increased risk of vascular dementia as
      a result of ischemic stroke and other cerebrovascular events or lesions. However,
      there is insufficient epidemiologic evidence indicating that blood pressure is
      involved in the etiology of Alzheimer's disease. Clinical studies suggest that
      episodes of hypotension may cause cerebral hypoperfusion and play a role in the
      development of dementia. Lowering of blood pressure in dementia, especially
      Alzheimer's disease, may be due to the dementia process itself or to the
      characteristics of the disease. Recent large clinical trials have shown that
      antihypertensive drugs may not significantly affect cognitive performance, but no
      data are available regarding their potential effects in decreasing the risk of
      dementia by lowering the incidence of cerebrovascular events. Some data suggest
      that the blood pressure-dementia relationship may be age-dependent.

PMID- 9161471
TI  - Risk of malignant transformation in patients with monoclonal gammopathy of
      undetermined significance.
AB  - The acturial probability of malignant transformation was analyzed in a series of
      263 patients with monoclonal gammopathy of undetermined significance (MGUS) over
      a 15-year period and followed from 5 to 20 years. At a median follow-up of 11.5
      years, 157 patients (59.7%) had died of causes unrelated to MGUS, 47 (17.9%) were
      still alive and presented no increase in monoclonal component, 11 (4.1%)
      presented an increase in monoclonal component without evidence of malignant
      immunoproliferative disease, and 48 (18.3%) had developed a malignant
      transformation of MGUS. In particular, MGUS evolved into 35 cases of multiple
      myeloma, two of solitary plasmacytoma of the bone, four of macroglobulinemia,
      three of malignant lymphoma, two of amyloidosis, one of chronic lymphocytic
      leukemia, and one of plasma cell leukemia. The cumulative incidence of malignant
      transformation was 18.3%; and the actuarial risk of malignant transformation was
      6.1, 15.4, and 31.3% at 5, 10 and 20 years, respectively. The multivariate
      regression analysis according to Cox's proportional hazard model selected among
      22 different variables established at initial diagnosis of MGUS only age as the
      factor significantly (P < 0.011) and negatively (b = -1.104) related to the risk
      of developing a malignant immunoproliferative disease. Therefore, patients with
      MGUS present an increased risk of developing a malignant lymphoproliferative or
      plasma cell proliferative disease, and MGUS could be considered a pre-neoplastic
      condition. Since no clinical or laboratory features are able to identify in
      advance the patients at high risk of disease progression, each patient must be
      followed up periodically and over an indefinite period.

PMID- 9161472
TI  - Possible monocytic origin of chondrosarcoma: in vitro transdifferentiation of HLA
      DR blood monocyte-like cells from a patient with chondrosarcoma, into neo
      fibroblasts and chondrocyte-like cells.
AB  - Nodules and multilayered areas composed of fibroblasts and chondrocyte-like cells
      embedded in an abundant extracellular matrix appeared spontaneously in in vitro
      culture of mononucleated blood cells taken from a patient with chondrosarcoma.
      Using specific antibodies it was demonstrated that the neo-fibroblasts which
      developed in the culture resulted from a direct transdifferentiation of monocytes
      expressing HLA-DR specificity. The experiment was carried out twice, once before
      surgery and then two years later. In both cases the spontaneous
      transdifferentiation of HLA-DR monocytes into neo-fibroblasts was observed.
      Previously it was shown that normal monocytes were also able to give rise in
      vitro to neo-fibroblasts. However, the latter are normally rapidly destroyed by
      cell-cell contact with T-cells. Normal T-cells adhere to normal neo-fibroblasts
      by which they are finally engulfed. As a result, the neo-fibroblasts lose their
      fibroblastic shape, no longer adhere to their support and die. Therefore the
      abnormal proliferation and persistence of neo-fibroblasts in pathological
      situations such as the present case may result either from an intrinsic defect in
      monocytes, T-cells or both. The question is whether or not this
      transdifferentiation process observed in vitro accounts for the development of
      chondrosarcoma in vivo. The present results suggest that in vivo chondrosarcoma
      may start in a necrotic zone (resulting for instance from trauma) and attract HLA
      DR monocytes, where they accumulate and transdifferentiate into neo-fibroblasts
      and chondrocyte-like cells. The uncontrolled transdifferentiation of these HLA-DR
      monocytes resulting from a dysregulation of the immune system is probably linked
      to the malignant process which may have a retroviral origin. The question is
      raised regarding the embryologic origin of this special sub-population of blood
      monocytes in which pluripotential capabilities are retained; its origin may
      differ from that of the other circulating monocytes.

PMID- 9161473
TI  - [Detecting hepatitis C virus RNA by in situ hybridization: a critical analysis].

PMID- 9161474
TI  - Focal liver disease: neural network-aided diagnosis based on clinical and
      laboratory data.
AB  - OBJECTIVES: The purpose of this study was to evaluate the use of clinical and
      laboratory data in the diagnosis of benign or malignant focal liver disease.
      METHODS: Diagnosis was made by artificial neural network (NN), a system of simple
      computing units connected in a specific structural network. Seven clinical and
      laboratory variables were retrospectively studied in 172 patients with a liver
      mass (93 benign, 79 malignant) detected with ultrasound. The diagnostic efficacy
      of NN was compared with a score based on the logistic regression model (Beaujon
      score). RESULTS: Although the sensitivity of the Beaujon score and the neural
      network was similar (4 malignant tumors inversely classified), neural network
      aided diagnosis was characterized by higher specificity and accuracy
      (respectively 98.9% vs 82.5%, P < 0.001, and 97.1% vs 88.4%, P < 0.002).
      CONCLUSION: In patients with a hepatic mass, neural network is a valuable method
      for differentiating malignant and benign tumors.

PMID- 9161475
TI  - [Ultrasonographic anomalies of intrahepatic biliary ducts: contribution of the
      comet-tail image].
AB  - OBJECTIVES: The aim of this study was to evaluate the sensitivity and specificity
      of the ultrasound intrahepatic bile duct wall comet-tail artifact for the
      diagnosis of biliary disease. METHODS: All subjects who underwent upper abdominal
      ultrasound examination were included in the study over an 18-month period. The
      presence or absence of the comet-tail artifact (that is hyperechoic pattern with
      several parallels lines, constant, lining on the intrahepatic biliary ducts) was
      noted. RESULTS: Fourteen thousand four hundred and ninety-eight patients were
      included. The comet-tail artifact was only found in 10 of the 14 211 patients
      without biliary tract disease (99.9% specificity), but in 35 of the 287 patients
      with biliary disease (12.2% sensitivity). The positive predictive value for the
      diagnosis of biliary tract disease was 77.7%. The artifact was associated with an
      angiocholitis in 83% of the patients. CONCLUSION: Despite its low sensitivity,
      the sonographic comet-tail artifact of the intrahepatic bile duct wall was
      strongly correlated with the presence of biliary disease. This artifact may be
      related to an enlargement of the bile duct wall.

PMID- 9161476
TI  - [Acute fatty liver in pregnancy].

PMID- 9161477
TI  - [Helicobacter pylori, achlorhydria and gastric atrophy: what kind of "menage a
      trois"?].

PMID- 9161478
TI  - [Comparison between spiral x-ray computed tomography and endosonography in the
      diagnosis and staging of adenocarcinoma of the pancreas. Clinical preliminary
      study].
AB  - OBJECTIVE: To determinate in a retrospective clinical study the benefit of
      helical-CT for the diagnosis and staging of pancreatic carcinoma compared with
      endoscopic ultrasonography. METHOD: Results of helical-CT and endoscopic
      ultrasonographic investigations relative to 24 cases of histologically proved
      adenocarcinoma were reviewed. The criteria studied were: a) existence of a
      pancreatic mass, b) diagnosis of malignancy, c) existence of vascular
      involvement, d) lymph node involvement. Statistical analysis (binomial test) was
      performed in 24 patients for the assessment of mass and malignancy and in 10
      patients for the assessment of vascular involvement (9 patients who underwent
      surgery and one patient with a positive arteriography). RESULTS: For diagnosis of
      pancreatic mass both methods were equivalent: 91.5% (22 cases out of 24) for
      helical-CT and 87.5% (21 cases out of 24) for endoscopic ultrasonography. Two
      pancreatic masses were seen only with endoscopic ultrasonography. Their size was
      under 3 cm. Two of the 3 masses not seen with endoscopic ultrasonography were
      infiltrative lesions measuring more than 3 cm. Helical-CT was significantly
      superior to endoscopic ultrasonography for the diagnosis of malignancy (96% vs
      71%) (P = 0.035). The accuracy of helical-CT for vascular involvement was
      significantly superior to endoscopic ultrasonography (90% vs 40%) (P = 0.031).
      Endoscopic ultrasonography underestimated vascular involvement in 5 cases:
      mesenterico-portal confluence (3 cases), superior mesenteric artery (2 cases). In
      the 6 cases with histologically proved lymph node involvement, endoscopic
      ultrasonography (6 correct assessments) was superior to helical-CT (3 correct
      assessments). CONCLUSION: This study confirms the complementarity of helical-CT
      and endoscopic ultrasonography for the diagnosis of pancreatic carcinoma. It
      suggests that helical-CT is superior to endoscopic ultrasonography for diagnosis
      of malignancy and assessment of vascular involvement and endoscopic
      ultrasonography is superior to helical-CT for diagnosis of lymph node
      involvement. These preliminary results have to be confirmed by a prospective
      study including a large number of patients with surgical correlation.

PMID- 9161479
TI  - [Interleukin-8 is an important inflammatory mediator in hemorrhagic rectocolitis
      and Crohn disease].
AB  - OBJECTIVES: The aim of the study was to assess in vitro the production of
      interleukin 8 in Crohn's disease and ulcerative colitis. PATIENTS AND METHODS:
      Interleukin 8 concentrations (measured by ELISA) were evaluated in the culture
      supernatants of: a) peripheral blood mononuclear cells from 13 patients with
      Crohn's disease, 7 patients with ulcerative colitis and 7 controls, b) organ
      cultures of inflamed (22 Crohn's disease, 15 ulcerative colitis) and uninflamed
      (21 Crohn's disease, 9 ulcerative colitis, 15 controls) intestinal mucosal
      biopsies. RESULTS: In patients with Crohn's disease and ulcerative colitis, the
      production of interleukin 8 by peripheral blood mononuclear cells and inflamed
      mucosa was higher than in controls (P < 0.01) without statistical difference
      between Crohn's disease and ulcerative colitis. Interleukin 8 production by
      normal mucosa was not different between the 3 groups. Interleukin 8
      concentrations in the supernatants of organ culture were positively correlated to
      an endoscopical and a histological inflammatory index as well as to tumor
      necrosis factor, interleukin 1 and 6 concentrations. CONCLUSION: These results
      support the notion that interleukin 8 plays an important role in the pathogenesis
      of inflammatory bowel disease.

PMID- 9161480
TI  - [Helicobacter pylori infection and gastric acid secretion].

PMID- 9161481
TI  - [Association of hepatic adenomatosis and hepatoportal sclerosis in a woman with
      incontinentia pigmenti].
AB  - We report the case of the association of three uncommon diseases in a young
      woman: incontinentia pigmenti, portal hypertension due to hepatoportal sclerosis,
      and liver adenomatosis. Incontinentia pigmenti is a hereditary genodermatosis
      with pigmentary cutaneous lesions and dysmorphic malformations. In our patient,
      among liver abnormalities, there were blood biochemical alterations, portal
      hypertension, and initially neo hepatic nodular lesions. Histological examination
      of the surgical liver specimen showed several adenomas and fibrosis of the portal
      tracts with portal vascular changes. The etiopathogenic nature of the
      adenomatosis and hepatoportal sclerosis is unclear. As a general rule, hepatic
      adenomatosis is associated with normal liver. We hypothesize that the adenomas
      could be secondary to changes in hepatic vascularisation.

PMID- 9161482
TI  - [Gallbladder involvement in Crohn disease].
AB  - We report the case of a young woman with Crohn's disease involving the entire
      digestive tract and with associated lesions of the liver, pancreas and
      gallbladder. This latter lesion led to acute cholecystitis which required
      cholecystectomy. The histo-pathological examination showed granulomas with
      multinucleated giant cells in the lamina propria. This observation illustrates a
      severe and extended form of Crohn's disease involving the entire digestive tract
      as well as the liver, the pancreas and the gallbladder.

PMID- 9161483
TI  - [Sudden deafness induced by interferon-alpha in viral hepatitis C].

PMID- 9161485
TI  - [Persistent increase of serum activity of aminotransferases disclosing muscular
      diseases in children and adolescents].

PMID- 9161486
TI  - [Upper dysphagia disclosing Horton disease].

PMID- 9161484
TI  - [Regressive pseudobulbar syndrome associated with acute viral hepatitis B].

PMID- 9161487
TI  - [Value of endosonography in the diagnosis of duodenal duplication in adults].

PMID- 9161488
TI  - [Wegener's disease: a rare cause of granulomatous colitis].

PMID- 9161489
TI  - [Acute necrotic pancreatitis and althiazide].

PMID- 9161490
TI  - [Primary prevention of colorectal cancer].

PMID- 9161492
TI  - [Peritoneal carcinosis treated by complete excision and immediate postoperative
      intra-peritoneal chemotherapy. Phase II study in 54 patients].
AB  - OBJECTIVES: The short term prognosis of peritoneal carcinomatosis whose classical
      treatment is intravenous chemotherapy, is poor (mean survival of 6 months). The
      aim of this study was to report the results of a phase II prospective study in
      which peritoneal carcinomatosis was managed with complete reductive surgery
      associated with treatment of the residual microscopic disease with immediate
      intraperitoneal postoperative chemotherapy. PATIENTS AND METHODS: Fifty-four
      patients with peritoneal carcinomatosis from miscellaneous origins, were treated
      between January 1993 and April 1996. Major peritoneal carcinomatosis was
      important, clinically evident, but without extraperitoneal localization in 29
      cases. It was moderate, fortuitously discovered during a laparotomy for an
      extraperitoneal recurrence in 25 cases. Immediate intraperitoneal postoperative
      chemotherapy was carried out continuously during 5 days, with 900 ml/m2 of ringer
      lactate, with either mitomycine C and 5-fluorouracil, or doxorubicin and
      platinum, according to histology. The treatment was complete in 91% of cases.
      RESULTS: Three patients died during the hospitalization (5.5%), and a high
      morbidity (61%) was observed, with 35% intra-abdominal complications
      necessitating surgery in 13% of the patients. The postoperative complications
      were correlated with the extension of the cytoreductive surgery (P < 0.001).
      After a mean follow-up of 12.3 months, 13 patients died. The 2-year survival rate
      was 50%. Survival was related to the importance of the peritoneal carcinomatosis
      (P < 0.01) and was identical for patients with isolated peritoneal carcinomatosis
      and for patients with moderate peritoneal carcinomatosis associated with resected
      extra-peritoneal disease. The incidence of recurrence of peritoneal
      carcinomatosis was 30% at 2 years, showing the efficiency of this new procedure
      to treat peritoneal carcinomatosis. CONCLUSIONS: Complete cytoreductive surgery
      with immediate intraperitoneal postoperative chemotherapy is a promising
      treatment of peritoneal carcinomatosis. However it appears that: a) it is a
      difficult treatment for patients and for physicians, b) its efficiency will be
      asserted only with a randomized study (currently ongoing), that only allows to
      suppress selection bias, c) it is able to cure some groups of peritoneal
      carcinomatosis (probably 20%), that will be difficult to identify, and d)
      improvement of immediate intraperitoneal postoperative chemotherapy is possible
      (mainly with hyperthermia). The main advantage of immediate intraperitoneal
      postoperative chemotherapy is that, after proving its efficiency, easy widespread
      use will be assured.

PMID- 9161493
TI  - [Aspirin, non-steroidal anti-inflammatory agents and colonic carcinogenesis].

PMID- 9161491
TI  - [Digestive cancers in France. Geographic distribution and estimation of national
      incidence].
AB  - OBJECTIVES: The purpose of this study was to compare the incidence of digestive
      cancers in 9 French departments and to give an estimate of this incidence for the
      whole of France, based on this data. METHODS: This study focused on the 1983-1987
      period. The record quality for the 9 included registries (Calvados, Coted'Or,
      Doubs, Haute-Garonne, Herault, Isere, Bas-Rhin, Somme, Tarn) has been assessed by
      the National Committee of Registries. The crude incidence rates and those
      standardized according to the world population have been worked out per
      localization and per sex. Incidence and mortality rates per department as well as
      mortality rates for the whole of France have enabled the assessment of the
      incidence and number of new digestive cancer cases per year. RESULTS: Esophagus
      and liver cancers are distinguished by large incidence disparities, fluctuating
      in a ratio of 1 to 5, and by a high sex ratio. In other localizations, incidence
      rates vary in a ratio of 1 to 2. The incidence rates of digestive cancers were
      especialy high in the Bas-Rhin department. They tended to be higher in Cote-d'Or,
      Doubs, Calvados and Somme, than in Haute-Garonne. Herault and Tarn. The estimated
      number of digestive cancers was 30,071 in males and 19,951 in females: colorectal
      cancer was particularly frequent, 14,179 cases and 12,228 cases, respectively.
      CONCLUSION: There are some geographical variations, from one region to another,
      in digestive cancer incidence in France more pronounced for esophagus and liver
      cancers than for other localizations. Because of its frequency, colorectal cancer
      represents a serious problem for public health.

PMID- 9161494
TI  - [Does breast feeding increase the risk of transmission of hepatitis B virus
      chronic carrier state?].

PMID- 9161495
TI  - [Congenital cystic dilatation of the common bile duct. Radio-anatomical
      correlations in 14 patients].
AB  - OBJECTIVES: The aim of this study was to compare imaging and pathological results
      of congenital cystic enlargement of the biliary tract to determine the best
      preoperative management strategy. PATIENTS AND METHODS: Radiological findings of
      14 cases treated by surgery were reviewed. Radiological examinations were
      reviewed: ultrasound (n = 20), computed tomography (n = 13), endoscopic
      ultrasound (n = 8), endoscopic retrograde cholangiopancreatography (n = 10),
      percutaneous transhepatic cholangiography (n = 3), peroperative cholangiography
      (n = 11). Imaging and surgical or pathological correlations were obtained with
      regard to topographical type using Todani's classification, pancreatobiliary
      junction, and associated diseases, especially biliary malignancies (cystic wall
      and gallbladder). RESULTS: Cystic enlargement of the biliary tract was type Ia in
      2 patients, type Ib in 1, type Ic in 4, type IVa in 5, and type IVb in 2. The
      radio-pathological correlation was excellent for the topographical type, and
      quite good for intrahepatic extension. An abnormal pancreatobiliary junction was
      identified in 5 cases, and visualized before surgery in I case. This junction was
      not opacified pre- or pre-operatively in 7 cases. Gallbladder stones were present
      in 2 cases, choledocal stones, in 2 cases, and intrahepatic stones in one cases,
      always seen on ultrasound. Malignant degeneration was present in the cyst in one
      case in the pathological specimen, but was not visualized by imaging procedures
      or peroperatively; one intrahepatic degeneration was visualized on CT and
      histologically proven in the surgical specimen. CONCLUSION: Ultrasound and CT
      allow positive diagnosis of cystic enlargement of the biliary tract, and
      diagnosis of intrahepatic cyst and associated diseases. The bifurcation extension
      and the study of pancreatobiliary junction require peroperative or retrograde
      cholangiography.

PMID- 9161496
TI  - [Procedure to follow in isolated increase of serum activity of gamma-glutamyl
      transpeptidase].

PMID- 9161497
TI  - [Recurrent lower digestive hemorrhage in young adults: a surgical indication].
AB  - The cause of low digestive bleeding remains unknown despite numerous
      investigations in less than 15% of cases. The case of a 22-year-old young female
      who presented 3 episodes of low digestive bleeding during a 25 months period,
      without any cause identified despite numerous investigations, is presented.
      Laparoscopy performed to establish a diagnosis showed a large Meckel's
      diverticulum which was removed. In adults, Meckel's diverticulum causes
      uncommonly symptoms and are revealed by an episode of digestive bleeding in less
      than 10% of cases. After several episodes of low digestive bleeding, a surgical
      procedure can be proposed, by coelioscopy better than laparotomy, to look for
      Meckel's diverticulum. This observation shows that this attitude, recommended in
      children, can be proposed also in young adults.

PMID- 9161498
TI  - [Hepatic distomatosis of tumor form after prolonged treatment with corticoids].
AB  - A 49-year woman, living in Cameroun and treated by steroids for connective tissue
      disease, was admitted for a liver mass and epigastric pain. An increase in blood
      count of eosinophils (1,590.10(9)/L) was observed. Imaging examination showed the
      presence of a voluminous, multilocular, and heterogeneous hepatic lesion.
      Pathological examination of the liver showed no evidence of tumor but revealed a
      rounded cuticle remnant, compatible with bilharziosis eggs or loase transversal
      section, and Charcot-Leyden's crystals. Due to the uncertainty of diagnosis, a
      right hepatectomy was performed. Pathological and parasitological examination of
      the surgical specimen confirmed the diagnosis of hepatic distomatosis, with
      typical eggs of Fasciola hepatica within necrotic tissue, surrounded by
      eosinophilic inflammatory infiltrates. Specific serology was positive. The
      presence of intraparenchymatous eggs was unusual and reflected the ectopic
      migration of a mature fluke into the hepatic parenchyma, even though the worm was
      not found in the surgical specimen. Serology for fascioliasis should be performed
      in any patient suffering from hepatic lesions with eosinophilia.

PMID- 9161499
TI  - [Acute cytolytic hepatitis caused by coumarin. 2 cases].
AB  - Coumarin is a drug which is extensively used to treat lymphedema. We report two
      cases of acute hepatitis probably due to coumarin. Two women, 40 year and 45 year
      old, were treated with 90 mg/d of coumarin for 5 months. Clinical features
      included jaundice, pruritus, and diarrhea. A marked increase in serum
      aminotransferases was observed (ALT: 30 and 100 times the upper limit of normal,
      respectively). Coumarin withdrawal was rapidly followed by a favorable outcome in
      both cases. Rechallenge in one case induced a relapse of symptoms and liver test
      abnormalities. Coumarin can induce acute cytolytic hepatitis.

PMID- 9161500
TI  - [Abdominal emergencies and Von Recklinghausen neurofibromatosis].

PMID- 9161501
TI  - [Colonic metastasis from kidney cancer. Presentation of 2 cases].

PMID- 9161502
TI  - [Benign cystic lymphangioma in a patient with acute intermittent porphyria].

PMID- 9161503
TI  - [Increase of serum alpha-fetoprotein in a patient with acinar cell carcinoma of
      the pancreas].

PMID- 9161504
TI  - [Bile duct metastasis of pancreatic leiomyosarcoma].

PMID- 9161505
TI  - [Chemoembolization of hepatic metastases of small intestine leiomyosarcoma. 2
      cases].

PMID- 9161506
TI  - [Acute hepatitis caused by Solupred in a patient with Crohn disease].

PMID- 9161507
TI  - [Cytolytic hepatitis of immuno-allergic mechanism caused by fluindione].

PMID- 9161508
TI  - [Should hepatitis C be screened? Value of hepatitis C screening].

PMID- 9161509
TI  - [Should hepatitis C be screened? Risk factors of transmission of hepatitis C
      virus].

PMID- 9161510
TI  - [Should hepatitis C be screened? Hepatitis C: screening tools].

PMID- 9161511
TI  - [Should hepatitis C be screened? Analysis of oriented screening strategies for
      hepatitis C virus infection].

PMID- 9161512
TI  - [Should hepatitis C be screened? Socioeconomic analysis of different screening
      strategies for chronic hepatitis C in French population].

PMID- 9161513
TI  - [Should hepatitis C be treated? Which biological tests are useful before deciding
      or refuting a treatment with interferon-alpha in patients with chronic hepatitis
      C?].

PMID- 9161514
TI  - [Should hepatitis C be treated? Value of hepatic biopsy in the management of
      patients with chronic hepatitis C virus infection?].

PMID- 9161515
TI  - [Should Hepatitis C be treated? Objectives of antiviral treatments in hepatitis C
      virus infection].

PMID- 9161516
TI  - [Should hepatitis C be treated? What are indications of treatment in acute
      hepatitis C?].

PMID- 9161517
TI  - [Should hepatitis C be treated? What are indications of treatment in chronic
      hepatitis C?].

PMID- 9161519
TI  - [How should hepatitis C be treated? Treatment of chronic hepatitis C with
      therapeutic combinations].

PMID- 9161518
TI  - [How should hepatitis C be treated? Treatment of hepatitis C with interferon].

PMID- 9161520
TI  - [How should hepatitis C be monitored? Monitoring of non-treated hepatitis C].

PMID- 9161521
TI  - [How should hepatitis C be monitored? Monitoring of treated hepatitis C].

PMID- 9161522
TI  - [What are the precautions to be taken in hepatitis C?].

PMID- 9161523
TI  - [Hepatitis C: risk factors and value of screening].

PMID- 9161524
TI  - [Hepatitis C: screening tools].

PMID- 9161525
TI  - [Efficacy and psychosocial impact of hepatitis C screening].

PMID- 9161526
TI  - [Should hepatitis C be treated?].

PMID- 9161527
TI  - [Results of treatment of hepatitis C with interferon alone or combined with other
      drugs].

PMID- 9161528
TI  - [Monitoring of treated or non-treated chronic viral hepatitis C. 1: Monitoring of
      non-treated chronic hepatitis].

PMID- 9161529
TI  - [Monitoring of treated or non-treated chronic viral hepatitis C. 2: Criteria of
      efficacy and monitoring of treatment with interferon-alpha].

PMID- 9161530
TI  - [What are the precautions to be taken in hepatitis C?].

PMID- 9161531
TI  - [Hepatitis C: screening and treatment].

PMID- 9161532
TI  - [Hepatitis C: screening and treatment].

PMID- 9161533
TI  - [Selective peripheral neurotomy of the hamstring branches of the sciatic nerve in
      the treatment of spastic flexion of the knee. Apropos of a series of 11
      patients].
AB  - BACKGROUND: A series of 11 patients (9 adults and 2 children) were operated on by
      selective peripheral neurotomy for spastic knee in flexion. The objective of
      surgery was to restore bipodal stance and therefore walking for the adult
      patients and to improve walking for the diplegic children. METHODS: Spasticity
      was secondary to stroke or cranial trauma for the adult patients. The two
      children presented with Little disease. The delay between onset and surgery was
      on the average of 2 years. All the patients had a passive flexum of the knee of
      20 degrees, and an excessive spasticity of the hamstrings (average Held score of
      4.55). Peripheral selective neurotomies consist of a partial section of the
      spastic muscle's motor fascicles. The partial section concerns the afferent
      fibers to the spinal cord whose interruption leads to the disappearance of
      spasticity. The section also involves the motoneurones' axons and thus leads to
      partial denervation. RESULTS: The spasticity of the treated muscles disappeared
      in the 11 patients. Average follow-up was 16 months. The neurotomies led to
      improvement of walking without splint for 3 walking patients, and restored
      walking with a splint for 5 patients. One patient failed to walk. The two
      children had a dramatic improvement of their walk. CONCLUSION: Our results incite
      us to increasingly indicate this type of neurotomy in the treatment of the
      spastic lower limb.

PMID- 9161534
TI  - [Hydatid cyst of the spine and spinal cord. Study of 24 cases].
AB  - In this retrospective study, we report our experience of severe hydatid disease
      located to the spine and the adjacent spinal cord observed in 24 cases between
      1970 and 1994. In our series the sex ratio was predominant for males, and the
      mean age was 29 years. Clinically, the patients presented predominantly with a
      motor deficit. The diagnosis was assessed on radiological and biological
      investigations and was confirmed preoperatively. Hydatid serology was positive in
      7 out of the ten cases explored. On standard X rays, the bone lesions were
      frequent: lysis in 10 cases, vertebral deformation in 3 cases, costal invasion in
      5 cases, and paravertebral collection in 2 cases. These lesions were
      predominantly located at the thoracic level. Myelography confirmed a complete
      blockade in 8 out of 11 cases. When possible, the CT scan confirmed the bone
      lesion in all of the 10 cases explored, with an intrathecal cyst in 7 cases and a
      paravertebral collection in 8 cases. Magnetic resonance imaging was possible in
      one case only. Medical antihelminthic treatment was indicated as the sole
      treatment in one inoperable case. All the other patients were operated on, and
      the adjunctive specific medical treatment was associated in 5 cases. Using a
      posterior approach in 20 cases, the operative technique consisted in a complete
      removal (if possible) of the invaded bone and soft tissue, thus achieving a
      complete relief of the spinal cord compression. Complementary bone fixation was
      indicated in 2 cases. During the postoperative follow-up, two patients died from
      infection and trophic ulceration, 11 patients improved and 8 patients remained
      unchanged. In 5 cases, a reoperation was indicated and performed from 2 to 4
      times. Three patients were lost for follow-up. The severity of this affection is
      confirmed in the literature. A complete recovery is quite exceptional. The best
      treatment remains an active nationwide prevention of the disease.

PMID- 9161535
TI  - [Experimental radiosurgery in rats using gamma a "gamma knife". Description of a
      stereotactic device for small laboratory animals].
AB  - To allow the experimental use in rats of a Gamma Knife Radiosurgical Unit, a
      stereotactic device adapted from the conventional Kopf's device was developed. To
      control the accuracy of the coordinate system based on the De Groot's rat
      stereotactic atlas, experimental radiosurgical lesions were made on the left
      striatum. The isodose curve distribution of the 4 mm collimator was calculated
      with the dose planning software used in Gamma Knife and superimposed on the left
      striatum target. Doses of 200 Gy were administered to the left striatum in six
      rats. The results were evaluated 21, 34 and 47 days later. At 34 and 47 days
      necrotic lesions were exactly as targeted. In a second group of 48 rats receiving
      a doses of 100 Gy, no lesions were observed after 7, 15, 24, 31, 45 days.
      However, in all rats sacrificed 59, 72 and 90 days after day radiation, a
      necrotic lesion was always present and confirmed that at each time the lesions
      were precisely targeted. This apparatus allows precise and reproducible gamma
      irradiation lesion in rat brain without expensive and time consuming imaging
      techniques. This device provides a useful system to observe the experimental
      effects of radiosurgery on the central nervous system in rats.

PMID- 9161536
TI  - [Giant sacral schwannoma with pelvic extension. Therapeutic strategy. Apropos of
      a case].
AB  - A 48-year-old woman was admitted for acute urinary retention. Clinical pelvic
      examination disclosed a voluminous retro-rectal mass. Plain X-rays, pelvic
      echography, computerized tomography and MRI were all consistent demonstrating the
      presence of a 15cm-diameter lesion in the pelvic space with sacral erosion at S3
      S4 and extension in the sacral canal up to S2. After a preoperative embolization,
      the tumor was removed in a two-stage procedure. First, an anterior transabdominal
      approach dissected the superior and lateral aspects of the tumor. To make easier
      the intra-abdominal dissection and to avoid any rectosigmoid necrosis,
      hysterectomy and rectosigmoid section with an end-colostomy were performed.
      Lastly, a piecemeal removal of the whole tumor was achieved using a posterior
      approach. At 6 months postoperatively, she recovered a satisfactory urinary
      control and the colo-rectal anastomosis was then successfully performed.
      Clinically only a slight hypesthesia of the left perineum was present. In the
      recent literature, 21 cases were described with similar clinical presentation and
      similar technical problems to achieve a complete treatment. In the discussion,
      details of the surgical anterior and posterior approaches are given. Before
      deciding the most appropriate surgical approach for such a mass, a biopsy is
      useful to determine whether total removal is relevant. A preoperative
      embolization can help to reduce the duration of the procedure and the loss of
      blood.

PMID- 9161538
TI  - [Intradural extramedullary tuberculous abscess. Apropos of a case].
AB  - Intradural extramedullary tuberculous spinal abscess is rare and has a poor
      prognosis if not diagnosed early and treated adequately. We report the case of 13
      year-old boy who presented with an 8-month history of paraplegia. MR imaging
      demonstrated an intradural extramedullary spinal abscess in the mid-thoracic
      region. At operation, an encapsulated abscess was removed completely. The
      tuberculous nature was confirmed with microbiological testing. Postoperative
      antituberculous chemotherapy resulted in complete recovery. MR imaging can prove
      very helpful in early diagnosis of this condition, which is particular relevant
      in countries where tuberculosis is endemic.

PMID- 9161537
TI  - [Spinal epidural cavernous angioma. Apropos of 2 cases. Review of the
      literature].
AB  - We report 2 cases of spinal epidural cavernous angiomas revealed by paraplegia,
      and present the main cases reported in the literature since 1895. The diagnosis
      of this uncommon affection seems to be difficult to establish only upon clinical
      and radiological features. In spite of recent advances in neuroradiological
      imaging, these kinds of angiomas still remain an operative and histopathological
      discovery. A laminectomy was performed revealing a vascular lesion which was
      totally extirpated. Functional recovery was achieved in both cases.

PMID- 9161539
TI  - [Thoracic medullary epidermoid cyst. Apropos of a case with MRI and review of the
      literature].
AB  - We report the case of a 14 year-old patient presenting with a thoracic spinal
      cord compressing syndrome (T5-T6). The myelography and magnetic resonance imaging
      showed an intramedullary cystic mass. One year after the surgical excision of the
      capsule and an easy aspiration of the tumoral content, this patient had a good
      neurological recovery.

PMID- 9161540
TI  - [African neurosurgery. 1: Historical outline].
AB  - This outline of the history of African Neurosurgery explains the role that North
      Africa has played in the Middle Ages in the development of Neurosurgery, the
      origins of the development of the latter in twentieth century, and the delay that
      African Neurosurgery still shows at the present time in the majority of African
      countries. On the papyrus of the pharaonic era, we have found the description of
      some neurosurgical procedures such as trephination and brain aspiration by a
      transphenoidal approach used before mummification. It is particularly
      trephination which summarizes the ancient history of African neurosurgery, as it
      was widely used throughout the continent, practised and taught by healers in
      African tribes. The technical concepts of trephination are based, to a great
      extent, on the descriptions of Arab physicians of the Middle Ages. It was at that
      time (Middle Ages) that several Arab physicians such as Avicenne, Rhazes, and
      Avenzhoer described many types of nervous system diseases and the techniques to
      treat them. But it was mainly Abulkassim Al Zahraoui (Abulkassis) who was the
      pioneer of neurosurgery as he devoted one volume of his treatise (made up of 30
      volumes) to neurosurgery, a precise description of many aspects of neurosurgical
      pathology, its treatment, instruments and neurosurgical techniques. We have
      reported in this article five original extracts in Arabic which deal with skull
      fractures and their treatment, vertebro-medullary traumas and their treatment,
      hydrocephalus and its treatment, tumors of the skull vault and their treatment,
      and finally the basic knowledge of anatomy which is of great interest for a
      surgeon. The medical knowledge of that time which gave birth to medical schools
      and hospitals was transmitted progressively to Europe and played an important
      role in the development of medicine during the European Renaissance in the
      fifteenth and sixteenth centuries. During colonization, neurosurgical practice
      started and developed in many African countries, together with the development of
      the health system that the colonial forces initiated in general as soon as they
      had come to these countries. This neurosurgery practised in the departments of
      general surgery either by neurosurgeons or general surgeons took part in the
      birth and development of neurosurgery as an independent specialty, thanks to the
      combined efforts of some European and African pioneers. Modern neurosurgery was
      introduced and started to develop in African countries from 1960, and the
      teaching of this specialty in many African universities began between 1960 and
      1970.

PMID- 9161541
TI  - [African neurosurgery. 2: Current status and future prospects].
AB  - A survey conducted among African neurosurgeons shows that there are nowadays 500
      neurosurgeons in Africa, that is one neurosurgeon for 1,350,000 inhabitants, and
      70,000 km2. The distribution of these neurosurgeons shows a striking regional
      disparity: North Africa has 354 neurosurgeons for 119 million inhabitants, that
      is one neurosurgeon for 338,000 inhabitants, and South Africa has 65
      neurosurgeons for 40 million inhabitants, that is one neurosurgeon for 620,000
      inhabitants. Between these two areas where neurosurgery is developing quite well,
      we have the majority of African countries with a scanty density of neurosurgeons
      (81 neurosurgeons for 515 million inhabitants, that is one neurosurgeon for
      6,368,000 inhabitants). The Panafrican Association of Neurological Sciences
      "PAANS" brings together the African neurosurgeons. This continental African
      Association represents African neurosurgeons in the WFNS. In addition to this
      continental Association, there are national societies of neurosciences. However,
      there are only six Societies of Neurosurgery. Two systems of training exist in
      Africa: local training and training abroad. These two systems have unequal
      quality and specific difficulties which have already been pointed out. Among the
      optimistic elements which make us believe in the development of neurosurgery in
      Africa are the existence of a quite good level of neurosurgery at the two
      extremities of the continent (North Africa and South Africa), the development of
      neurosciences in the African universities, and the increasing interest that the
      international community bears to Africa in the last years. However, the real
      factor of optimism is the African neurosurgeons who should promote neurosurgery
      in their continent, at the level of their own countries by developing information
      and health education, setting their specialty in the education syllabus and
      health planning, and settling into active and performing societies. At the
      continental and international level, African neurosurgeons should
      institutionalize inter-African cooperation, expedite their continental
      association (PAANS), and further exchanges with the other continents through the
      SNCLF (Societe de Neurochirurgie de Langue Francaise). The latter, together with
      other associations such as the EANS (European Association of Neurosurgical
      Societies) and WFNS (World Federation of Neurosurgical Societies) could provide
      help to the development of Neurosurgery in Africa as far as training, exchanges,
      research and organization are concerned.

PMID- 9161542
TI  - The genus Cephaloleia (Coleoptera:Chrysomelidae) in Central America and the West
      Indies.
AB  - The species of Cephaloleia Chevrolat known to occur in Central America and the
      West Indies are revised and a key to the 88 species is presented. Most species
      are illustrated. Twenty new species of Cephaloleia are described: amblys,
      cylindrica, eumorpha, erugatus, facetus, formosus, lepida, scitulus, and weisei
      from Panama; delectabilis and presignis from Mexico; brunnea and rubra from
      Trinidad; immaculata, triangularis, and viltata from Costa Rica; splendida and
      uhmanni from Costa Rica and Panama; cyanea from Costa Rica, Colombia, and
      Venezuela; and varabilis from Panama and Colombia. Three new synonyms are given:
      abscissa Uhmann (= dilaticollis Baly), beckeri Weise (= gratiosa Baly), and
      quadrimaculata Uhmann (= fenestrata Weise). Lectotypes are designated for eleven
      species: belti Baly, consanguinea Baly, elegantula Baly, fulvicollis Weise,
      instabilis Baly, nigropicta Baly, postuma Weise, quadrilineata Baly, separata
      Baly, stenosoma Baly, and vicina Baly. Two species are transferred from Demotispa
      to Cephaloleia: coeruleata Sanderson and costaricensis Uhmann. Cephaloleia
      coeruleata (Sanderson) is renamed C. sandersoni.

PMID- 9161543
TI  - Preliminary taxonomy of Costa Rican Psychodidae (Diptera), exclusive of
      Phlebotominae.
AB  - 100 species of Psychodidae, not including the Phlebotominae, are recorded from
      Costa Rica. Keys are given for all the following taxa, except species of Maruina,
      and descriptions and illustrations are given for all new species: TRICHOMYINAE:
      1. Trichomyia triangularis, n.sp., 2. T. pseudodactylis, n.sp., 3. T. brevitarsis
      Rapp, 4. T. saurotis, n.sp., 5. T. tritruncula, n.sp., 6. T. xaniostylis, n.sp.,
      7. T. intricata, n.sp., 8. T. ptilotis, n.sp., 9. T. acanthostyla, n.sp., 10. T.
      clavellata, n.sp., 11. T. dolichakis, n.sp. PERICOMINI: 12. Pericoma hansoni,
      n.sp., 13. P. zumbadoi, n.sp., 14. P. hespenheidei, n.sp., 15. Syntomoza
      monteverdica, n.sp. MARUININI: 16. Maruina (Aculcina) amadora Hogue, 17. M. (A.)
      amada Hogue, 18. M. (A.) querida Hogue, 19. M. (A.) cholita Hogue, 20. M. (A.)
      muchacha Hogue, 21. M. (Maruina) chamaca Hogue, 22. M. (M.) chamaquita Hogue, 23.
      M. (M.) chica Hogue, 24. M. (M.) dama Hogue, 25. M. (M.) vidamia Hogue, 26. M.
      (M.) tica Hogue, 27. M. (M.) nina Hogue, 28. Alepia alfaroana (Dyar), 29. A.
      valentia, n.sp., 30. A. relativa, n.sp., 31. Arisemus spilotos, n.sp., 32. A.
      lepidotos, n.sp., 33. A. salazari, n.sp., 34. Caenobrunettia plegas, n.sp., 35.
      S. laselva, n.sp., 36. S. tropicalis, n.sp., 37. Armillipora selvica, n.gen.,
      n.sp., 38. Balbagathis sylvatica, n.gen., n.sp., 39. B. talamanca, n.sp., 40.
      Tonnoira bitenacula, n.sp., 41. T. plumaria, n.sp., 42. T. moragai, n.sp.
      TELMATOSCOPINI: 43. Duckhousiella furcatus (Kincaid), 44. Telmatoscopus
      mergacolis, n.sp., 45. T. clavatus, n.sp., 46. T. congruus, n.sp., MORMIINI: 47.
      Bryopharsos palpiculum, n.gen., n.sp., 48. B. claviformosum, n.sp., 49. B.
      clavigum, n.sp., 50. B. tritaleum, n.sp., 51. Eugenys clavellata, n.gen., n.sp.,
      52. Brunettia bistria, n.sp., 53. B. apiculata, n.sp. PSYCHODINI: 54.
      Philosepedon tritaxis, n.sp., 55. P. pandiculatus, n.sp., 56. P. tetartos, n.sp.,
      57. P. atopos, n.sp., 58. P. parifurcus, n.sp., 59. P. longistylus, n.sp., 60. P.
      ensiger, n.sp., 61. P. retusus, n.sp., 62. P. bicuspis, n.sp., 63. P. hamatus,
      n.sp., 64. P. ancepitis, n.sp., 65. P. pollicaris, n.sp., 66. P. bicalcaratus,
      n.sp., 67. P. dimorphus, n.sp., 68. P. tritenaculus, n.sp., 69. P. deceptrix,
      n.sp., 70. P. tripetalis, n.sp., 71. P. majorinus, n.sp., 72. Psychoda
      quiniversa, n.sp., 73. P. litotes, n.sp., 74. P. obeliske, n.sp., 75. P. setigera
      Tonnoir, 76. P. alternata Say, 77. P. alternata complex, 78. P. balaenica, n.sp.,
      79. P. laticaula, n.sp., 80. P. apparitia, n.sp., 81. P. spondea, n.sp., 82. P.
      articaula, n.sp., 83. P. stenostypis, n.sp., 84. P. cordiforma, n.sp., 85. P.
      bicordata, n.sp., 86. P. savaiiensis Edwards, 87. P. buxoides, n.sp., 88. P.
      incompta, n.sp., 89. P. mimica, n.sp., 90. P. laticeps, n.sp., 91. P. psilotes,
      n.sp., 92. P. rhis, 9. P. varablanca, n.sp., 97 P. bisacula, n.sp., 98, P.
      entolopha, n.sp., 99. P. aculeata, n.sp., 100. P. flagellata, n.sp.

PMID- 9161544
TI  - [Embolism and intramedullary femoral surgery].
AB  - All intramedullary femoral surgery entails embolic phenomena which explain
      peroperative collapses formally known as bone cement implantation syndrome, as
      well as perioperative fat embolism syndromes. Locally, the bigger the cavity is,
      the higher the number of accidents: 2.5-5 per cent for GUEPAR hinged-knee
      prosthesis, 1.75 per cent for total hip arthroplasty with long stem, and 0.1 per
      cent during classic THA with cement limited to the metaphysis. Anomalies in bone
      vascularization also increase risk: 10.5-13 per cent during prophylactic nailing
      for shaft metastases, 1-11.5 per cent during hemiarthroplasty cemented in
      osteoporotic bone of femoral neck fractures, and only 0.1 per cent during THA
      implanted because of arthrosis. Not only cement, but also rods, reamers, nails,
      implants, ultrasonic tool for cement extraction, increase the pressure inside the
      cavity. Methylmethacrylate is no longer the only incriminated factor, even if it
      is responsible for a major part of the compressive load. The intensity and
      duration of the pressure are correlated with the number of embolic phenomena and
      with measured cardiopulmonary parameters. The intracavity fat content is expelled
      (an empty cavity, as in THA revision, does not lead to embolic phenomena). Then
      filters through the intraosseous veins whose diameter limit the size of the
      extruded embolic phenomena. The ultrasonography of the inferior vena cava shows
      innumerable fine particles and thrombi which are already organized under the
      influence of procoagulant factors released from the operative shield and which
      remain crumbly. These emboli cross the cardiac cavities. Transesophageal
      echocardiography (TEE), of recent use, does quantify the amount of right atrial
      filling, duration of echogenesis and size of particles: the result is higher in
      patients who underwent cemented versus noncemented THA: however the embolism
      score is no an indicator of seriousness because it is not correlated with
      cardiorespiratory manifestations; TEE shows only one fourth of the patent foramen
      ovale, whereas the atrial septal defect is surely one of the most efficient
      systemic invasion mechanisms to produce perioperative fat embolism. Lung response
      is most often asymptomatic, even if all patients undergoing intramedullary
      surgery display an increase in pulmonary vascular resistance which is managed by
      the right heart only, as well as pulmonary (and sometimes systemic) microvascular
      fat obstruction. Common operating room monitoring procedures do not detect
      successive embolic phenomena before they cause pulmonary arterial hypertension
      which then has repercussions on the left heart and in turn causes peroperative
      hemodynamic accidents. Only pulmonary arterial pressure measurement with a Swan
      Ganz catheter gives early and durable signs of an intolerance to embolic load.
      Preventive treatment is surgical as there is an inverse relation between embolic
      marrow and marrow eliminated by large volume washes (which is often more
      effective than draining). Cement indications in older patients as well as the
      choice of fixation techniques in femoral fractures must take into account the
      cardio-pulmonary condition of the patient. Resuscitation procedures dealing with
      these complications end in the patient's death in half of the cases.

PMID- 9161545
TI  - [Sagittal balance of the spine].
AB  - PURPOSE OF THE STUDY: The authors examined the modifications of sagittal shape
      and muscular functions in different vertebral diseases in order to investigate
      their correlations and to specify the role of hip extension in standing posture.
      MATERIALS AND METHODS: We included 57 patients presenting various diseases, among
      which lumbar kyphosis, spondylosis and spondylolisthesis, backache and lumbar
      stenosis. We measured joint mobility (hip extension, lumbar flexion), muscular
      retractions (ilio-psoas, hamstrings, rectus femoris), and muscular strength
      (spine flexors and extensors, hamstrings, quadriceps femoris). On standing
      lateral x-rays, measurements were made of various spinal and pelvic parameters,
      among which the "pelvi-femoral angle", proposed by the authors for hip extension
      evaluation. RESULTS: There was a significant correlation between pelvi-femoral
      angle and pelvic backward tilting (r = 0.8037 p < 0.01). This angle can therefore
      be considered as fundamental for evaluation of sagittal posture. Characteristic
      abnormalities were found for each pathogenic group, notably for lumbar kyphosis
      and spondylolisthesis. DISCUSSION: Upright posture is secondary to hip extension
      and lumbar lordosis, and an optimal and economic standing posture is obtained
      when balance between these two phenomena is correct. In lumbar kyphosis pelvic
      modifications such as hip extension, and pelvic backward tilt-up arise
      compensating the anterior displacement of the center of gravity, while in
      spondylolisthesis, anterior displacement is secondary to sacral obliquity.
      CONCLUSION: It is very important to evaluate the pelvis position in sagittal
      spinal diseases, in order to understand postural deterioration mechanisms. Lumbar
      kyphosis and spondylolisthesis are two examples of failure of upright posture.

PMID- 9161546
TI  - [Bone marrow in patients with pseudarthrosis. A study of progenitor cells by in
      vitro cloning].
AB  - PURPOSE OF THE STUDY: The recent observations that osteoblasts develop from a
      stem cell found in the medullary stroma suggest that, as already suspected in
      classical histological studies, many consolidation mechanisms are based on bone
      marrow. Since cells characteristics can now be studied in tissue culture, it has
      become possible to investigate the activity of the bone marrow in non union. The
      working hypothesis for this study was: if the bone marrow plays a part in bony
      callus formation, bone marrow from non union site should manifest anomalous
      activity whatever the origin of the focus sampled. Therefore, the aim of this
      study was to seek in vitro, using cell cloning techniques, anomalies of bone
      marrow from non union site. MATERIALS: The study characterizes the bone marrow
      from 35 non union sites, not only with respect to the medullary stroma but also
      the hematopoietic compartment. In this study, we look for systemic anomalies
      which could explain susceptibility to non union, we also compare in vitro
      activity of bone marrow taken from non union with others samples taken from the
      iliac crest of the same patient. METHODS: The cell density in the bone marrow in
      these sites was studied in vitro with material taken from the non union site.
      Samples were taken by aspiration with a trocar located by image intensification.
      Assays of CFU-GM were chosen to quantify the hematopoietic activity of the
      marrow, and of CFU-F to quantify stroma cells activity. Cell densities in the non
      union site were compared to those in patients' own iliac crests, and also to
      iliac crests densities of a control population of bone marrow donors. RESULTS:
      The bone marrow of non union site contained low levels of progenitor cells.
      Especially surprising was that progenitors were also sparse in the bone marrow of
      the iliac crest of patients with non union, compared with control bone marrow
      donors. In several cases, certain general factors are probably responsible for
      the abnormally low levels of progenitor cells, not only in the non union site,
      but also in the iliac crest.

PMID- 9161547
TI  - [Treatment of congenital hip dislocation using Pavlik's harness. Long term
      results].
AB  - PURPOSE OF THE STUDY: After many years using Pavlik harness for treatment of
      congenital hips dislocation, it is important to evaluate long-term results,
      failure causes and factors responsible for avascular necrosis. MATERIAL: One
      hundred and forty one children were treated by this mean (159 dislocated hips, 30
      acetabular dysplasia). The follow up was 74 months (12-175). METHODS: In this
      study, the severity of the dislocation was evaluated by antero-posterior
      radiographs of the pelvis. The importance of proximal dislocation was measured by
      the distance from the top of the proximal femoral metaphysis to the Y line and
      the lateralization by the distance from the medial border of the proximal femoral
      metaphysis to the ischium. Results were appreciated using Severin classification
      modified by Kasser and Mose's circles. Several factors as age at the beginning of
      treatment, sex, previous treatment, passive abduction of the hip, amount of
      dislocation were statistically evaluated (chi 2 and P test). RESULTS: Of 159
      dislocated hips, 10 (6.3 per cent) were not reduced by the harness. Temporary
      growth modifications and avascular necrosis were observed in 24 (16.1 per cent)
      of 149 reduced hips. We shall add to these, 3 avascular necrosis in 10 hips which
      were not reduced in the pavlik harness and 2 avascular necrosis which occurred in
      normal hips. This complication was not encountered in dysplasic hips without
      dislocation. Using Severin classification, there was 61 excellent, 33 good and 5
      fair results in the group of 99 hips followed for more than 72 months. Of all
      growth anomalies and avascular necrosis, only half of them keep sequelae at the
      last follow-up. DISCUSSION: Some factors as age, sex, previous treatment have no
      incidence in the number of failures and avascular necrosis. On the contrary,
      passive abduction of the hip, severity of the dislocation were responsible for
      most of these complications. Pavlik harness must be used with circonspection. It
      can be used only where passive abduction is superior to 30 degrees and distance H
      superior to 4 mm. In other cases, it is preferable to use progressive traction.
      CONCLUSION: Pavlik harness is widely used for treatment of congenital hip
      dislocation. Reduction can be obtained as stabilisation and correction of
      acetabular dysplasia. The risk for avascular remains relatively high. The use of
      the harness needs a rigourous choice of indications.

PMID- 9161548
TI  - [Paralysis of the brachial plexus caused by supraclavicular injuries in the
      adult. Long-term comparative results of nerve grafts and transfers].
AB  - PURPOSE OF THE STUDY: Recovery of active elbow flexion constitutes the first
      priority in microsurgical repair after closed injuries of the supraclavicular
      brachial plexus in adults. However, there are many controversial issues between
      the proponents of nerve grafting from available roots, and the proponents of
      nerve transfer. MATERIAL AND METHODS: The results concerning elbow flexor muscle
      recovery following microsurgical nerve repair of supraclavicular brachial plexus
      lesions were analysed in 62 patients. The average age at operation was 23 years
      old and the average delay between trauma and nerve repair was 7 months. Nerve
      grafting from C5 or C6 was performed in 43 patients. Nerve transfer using 3
      intercostal nerves was done in 10 patients and using the spinal accessory nerve
      in 7 patients. A combination of both techniques was performed in 2 patients.
      Conventional sural nerve grafts were used every time. Functional evaluation was
      based on the assessment of active range of motion including flexion and
      supination, and on the assessment of maximum isotonic strength of the elbow
      flexors. RESULTS: With an average follow up of 8.5 years (range from 3 to 16
      years) the average functional score of the elbow flexors was 4.4 out of a
      possible 11. Sixty six percent of patients had a strength recovery of M3 or more.
      Nerve repair using nerve graft from a non avulsed root seems to give better
      functional scores than nerve transfer from intercostal nerves or spinal accessory
      nerve using interpositional nerve graft, even if the differences were not
      statistically significant. DISCUSSION: In order to restore elbow flexion in case
      of supraclavicular brachial plexus lesion, nerve graft from an available root
      should be preferred to nerve transfer with interpositional nerve graft, when no
      avulsion exists among C5 and C6. Nerve transfer with interpositional nerve graft
      to the musculocutaneous nerve is indicated in case of avulsion of one or more
      roots among C5 and C6.

PMID- 9161549
TI  - [Recent palmar dislocations of the proximal interphalangeal joint].
AB  - PURPOSE OF THE STUDY: Recent anterior dislocations of the proximal
      interphalangeal (PIP) joint are uncommon injuries. Chronic and irreducible
      dislocations have been most often reported. This study aims to precise the
      anatomic and radiologic aspects of these lesions about three cases, and to
      compare these cases and their treatment with thirteen cases published in the
      literature between 1966 and 1994. MATERIAL AND METHODS: Three patients presented
      an anterior dislocation of the PIP joint after direct or twisting traumatism. One
      had an avulsion of the central slip of the extensor tendon and remained unstable
      after closed reduction needing pin fixation. Two had a longitudinal tear between
      central and lateral bands of the tendon with an entrapment of the condyle of the
      proximal phalanx, and the dislocations were irreducible. After open reduction,
      the joint was stable. RESULTS: The first case showed a limited flexion after
      three months. In the two other cases without rupture, full range of motion was
      recovered after two months. DISCUSSION: These cases have been compared with
      thirteen cases of recent papers from nine authors. Two types of anterior
      dislocations of the PIP joint may be described. TYPE I: Without rupture of the
      central slip fo the extensor tendon. One distal condyle of the proximal phalanx
      is entrapped between the central slip and a lateral band of the extensor tendon,
      that are separated by a longitudinal partial tear. The deformity is made by
      flexion, axial rotation and lateral displacement of the middle phalanx. Open
      reduction is required and may carry out good functional result. TYPE II: With
      rupture of the central slip of the extensor tendon. These very unstable lesions
      need a fixation after closed or open procedure. The treatment is often lately
      carried out, and the results not so good as in type I. CONCLUSION: Two different
      types of PIP joint anterior dislocations are described. Earlier diagnosis and
      surgical treatment can allow early rehabilitation and better final functional
      results.

PMID- 9161551
TI  - [Osteosynthesis of internal malleolar fracture by staplers].
AB  - PURPOSE OF THE STUDY: Rigid medial and lateral fixation should stabilize the
      syndesmosis without further additional supplementation. We used Titanium staples
      for medial malleolar fixation. MATERIAL: This study included 21 medial malleolar
      fractures (6 isolated medial malleolar fractures). Ankle fractures were
      classified according to Weber's system for lateral malleolar fracture. TECHNICAL:
      Tension band was used for Weber A lateral malleolar fracture and a plate for
      Weber B and C. One Weber A fracture was stabilized by staples. After reduction
      with clamps, three staples are placed perpendicular to the fracture line. All
      medial malleolar fractures were treated by staples including comminutive
      fractures or fractures who extended proximally into the tibia pilon. Only three
      transversal fractures of the anterior rim were treated by staples. Closure was
      made without any drainage. A below the knee cast was placed for 6 weeks. RESULTS:
      All fractures healed without further displacement. According to Weber Score,
      eleven ankle had an excellent result, seven a good result and three a bad result.
      We never removed the staples except in one case of technical error. DISCUSSION:
      Titanium staple present an attractive alternative for medial malleolar fixation.
      Plaster cast don't impair ankle function. Titanium staples are easy to use, are
      of little bulk and removal is not necessary. Skie et al. described three types of
      anterior rim fracture: one transversal and two oblique. The small size of the
      fragment makes reduction difficult to maintain, and impacted staple tends to
      displace laterally this small fragment. In this series we stapled only transverse
      fracture of the anterior rim (three times). But even in this case, it is
      difficult to maintain reduction during stapling. In case of lass of reduction,
      removal of the staple is responsible for fragmentation of the small fragment.
      Excluding the anterior rim fracture, other fractures, including T fractures and
      fractures who extend to the tibial pilon can be treated by this technique.
      CONCLUSION: Titanium staple is easy to use in medial malleolar fractures
      excluding anterior rim fractures.

PMID- 9161550
TI  - [Surgical treatment of ruptures of the Achilles tendon. Apropos of 42 cases
      treated by Bosworth's technique].
AB  - PURPOSE OF THE STUDY: There is no consensus on the treatment of acute ruptures of
      the Achilles tendon. We have chosen surgical technique with early muscle
      stimulation. This study analyses possibilities of functional recovery and
      complications in Athletes. MATERIALS AND METHODS: Between 1983 and 1994, we
      treated surgically 42 Athletes who had Achilles tendon ruptures with early
      musculo-tendinous stimulation. The 39 male and 4 female patients had a mean age
      of 41 years (range, 15 to 70). We have always used Bosworth's technique with
      gastrocnemius flap procedure. Immediately after surgery, weightbearing with below
      the-knee cast was initiated for 6 weeks followed by rehabilitation. RESULTS:
      There was no local major complication, deep vein thrombosis or pulmonary
      embolism. Only one patient suffered from a traumatic rerupture one month after
      surgery. Mean value of the calf atrophy was less than 1 cm. 93 per cent of
      patients returned to previous activity levels and 78.5 per cent of patients
      returned to their usual sport activity. DISCUSSION: Like this study recent
      results confirm the low complication and recurrence rate of the surgical
      treatment. Percutaneous technique and conservative treatments seem to be worse
      for rerupture and sportive functional recovery. Early muscle stimulation decrease
      morbidity and calf atrophy. Our protocol with weightbearing in ankle neutral
      position reduces calf atrophy. CONCLUSION: A rigid and stable reconstruction,
      allowing early weightbearing without equinus position seems to be a rational
      treatment for Achilles tendon rupture in athletes.

PMID- 9161552
TI  - [Osteoid osteoma of the intramedullary diaphyse in children].
AB  - We report 2 cases of uncommon osteoid osteoma in 2 children; they occurred at an
      exceptional age: 18 months and 2.5 years. They have also original location at the
      intramedullary diaphyseal tibial shaft. Osteoid osteoma is divided into cortical,
      medullary and subperiosteal location. Cortical osteoid osteoma is accompanied by
      intense reactive bone sclerosis, but medullary and subperiosteal types are
      associated with mild or non reactive bone sclerosis. In our cases, osteoid
      osteoma were associated with intense reactive bone sclerosis as noted in the
      cortical form.

PMID- 9161553
TI  - [Spontaneous elimination by the natural tracts of screws of anterior cervical
      osteosynthesis. Apropos of a case].
AB  - PURPOSE OF THE STUDY: The authors report a case of a wellknown but very unusual
      complication of cervical spine anterior osteosynthesis: spontaneous recurrent
      elimination of anterior fixation device through the gastrointestinal track, with
      good outcome. MATERIALS AND METHODS: The patient (75 years old) was operated on
      for cervical myelopathia due to cervical stenosis. Surgical treatment included an
      anterior release with corporectomy of C4, C5 and C6 and iliac graft insertion,
      and fixation using plate and screws. Immediate post-operative course was
      uneventful. Plate incurvation and rupture were observed during the second post
      operative month, with partial anterior migration of the lower screw. As the
      patient complained of dysphagia, removal of osteosynthesis was decided and
      scheduled 3 days later; however the screw was missing on a pre-operative
      radiograph. It was found on a routine abdominal X-Ray, and it passed out during
      the following week. Dysphagia disappeared in a few days and removal of
      osteosynthesis was given up for fear of oesophageal complications. Further
      evolution was favourable. Cervical fusion was obtained uneventfully. Post
      operative myelmogram showed a good canal enlargement. The patient was temporarily
      lost for follow-up and was asked for review 2 years later. Mild difficulty in
      swallowing saliva was still present without dysphagia. On routine cervical X-Rays
      another screw had disappeared again. Oesophagoscopy was proposed but not accepted
      by the patient because he felt not significantly disturbed. DISCUSSION AND
      CONCLUSION: Complications associated with oesophageal perforation may range from
      massive infection and death to spontaneous resolution. Erosion due to extruded
      bulky constructs leads to persistent fistula with abscess or septic diffusion.
      Perforation due to complete migration of small foreign bodies like screws gives
      possibility of spontaneous oesophageal closure and healing without significant
      morbidity. The spontaneous recurrent elimination of 2 screws gives to this
      observation a very outstanding feature.

PMID- 9161554
TI  - [Is current teaching of osteology a preparation for the study of musculoskeletal
      diseases?].

PMID- 9161556
TI  - [New targets of antiphospholipid antibodies].
AB  - "Antiphospholipid" antibodies (aPL) are a heterogenous group of autoantibodies
      with clinical importance because of their association with thrombotic events,
      both venous and arterial. Traditionally, aPL have been assayed using phospholipid
      dependent tests and are classified as lupus anticoagulants and anticardiolipin
      antibodies (ACA), based on the method of detection. Most antibodies associated
      with the aPL syndrome and detected in standard assays are actually directed
      against two phospholipid-binding plasma proteins, beta 2 glycoprotein I and
      prothrombin. These antibodies can also be detected in immunoassays (ELISA)
      utilizing purified protein antigens, in the absence of phospholipids. The main
      advantage of beta 2 GPI-ELISA compared with conventional cardiolipin-ELISA
      appearing from initial clinical studies is greater specificity for the aPL
      syndrome, due to (i) ignorance of "authentic" ACA that interact directly with
      cardiolipin; (ii) detection of species specific anti-beta 2 GPI antibodies poorly
      reactive with bovine beta 2 GPI in the cardiolipin-ELISA. Other proteins proposed
      as target antigens of aPL are protein C, protein S, annexin V, high- and low
      molecular weight kininogens, the latter being involved in the binding of
      antibodies to phosphatidylethanolamine. The possibility that particular
      autoantibodies (or combinations of autoantibodies) explain the observed clinical
      spectrum of the aPL syndrome is attractive, but much remains to be learned about
      their pathogenicity and origin in order to improve diagnosis and therapy.

PMID- 9161555
TI  - [Influence of seasons on risk of flare-up of systemic lupus: retrospective study
      of 66 patients].
AB  - PURPOSE: To establish the possible connection between visceral, arthro-cutaneous
      and biological spreading of systemic lupus (SL) and hours of sunlight. MATERIAL
      AND METHODS: Retrospective study of 66 SL patients, consisting of 52 visceral and
      14 arthro-cutaneous cases taking into account the chronological pattern of each
      new aggravation, based on 480 clinical records. RESULTS: Increased frequency in
      visceral aggravation was observed in the post-summer period (August-January) (n =
      57), as compared with the pre-summer period (February-July) (n = 25) (RR = 1.75,
      P = 0.006). This post-summer visceral aggravation was correlated with cutaneous
      affection (RR = 4.18) and absence of previous corticotherapy (RR = 3.97).
      Visceral and arthro-cutaneous aggravations taken together revealed a more
      disturbed immune balance pattern in the post-summer period (anti-dsDNA: 30 versus
      25.1 IU/L [P = 0.07]; C3: 0.83 vs 0.921 IU/L [P = 0.05]; C4: 0.146 vs 0.183 [P =
      0.05]), providing evidence of greater severity. Moderate thrombopenia (50-120
      10(9)/L) accompanying visceral SL with antiphospholipids (n = 33) was more
      frequent during the post-summer period, even in the absence of aggravation (P =
      0.03). The quarterly distribution of visceral aggravations was correlated with
      average hours of sunlight in the preceding quarter (P = 0.01). CONCLUSION: There
      is a post-summer increase in the frequency and severity of visceral SL spreading
      correlated to cutaneous exacerbation and sunlight.

PMID- 9161557
TI  - [Psychopathological disorders and coronary diseases].
AB  - The role of psychological factors in the genesis of coronary diseases has been
      considered for a long time. Friedman took it upon himself to describe a
      personality profile (pattern A) constituting a risk factor for coronary heart
      disease of which, however, the practical interest seems limited. The association
      of psychopathological conditions and coronary heart disease has on the other hand
      not been extensively studied. Recent epidemiological data show that anxiety and
      depressive states represent a high comorbidity with coronary heart diseases.
      Panic attacks remain underestimated; they seem to participate in a complex
      physiopathological mechanism along with ischemic coronary heart diseases. Recent
      studies have shown that the existence of a depressive illness during coronary
      heart disease and particularly in the time period following a myocardial
      infarction, constitutes an independent risk factor, thus increasing the mortality
      rate. The evolution of coronary heart disease seems greatly influenced by the
      existence of anxious or depressive states, the diagnosis and the treatment of
      these states represent a major interest towards a better management of coronary
      patients.

PMID- 9161558
TI  - [Periarteritis nodosa disclosed by epilepsy in a drug addict with hepatitis B and
      C virus carrier state].
AB  - The authors report a case of periarteritis nodosa (PAN) with an inaugural symptom
      of febril epilepsy. The patient was drug addict with hepatitis B and C virus. A
      toxoplasmic lesion originally noted on the cranial computed tomography scan was
      confirmed by cerebral magnetic resonance imaging showing encephalitis, and a
      diagnosis of periarteritis nodosa was suggested by clinical signs and laboratory
      data. The responsibility of hepatitis B virus in the genesis of this PAN seems
      quite certain whereas possible others factors such as hepatitis C virus or
      cocaine are discussed.

PMID- 9161559
TI  - [Raynaud syndrome complicated by digital gangrene during treatment with
      interferon-alpha].
AB  - In a 43-year old male suffering from idiopathic hypereosinophilic syndrome (HES)
      since 1984, successfully treated with alpha interferon (alpha IFN) for 32 months,
      a severe Raynaud's phenomenon of the four extremities occurred and eventually
      evolved into digital necrosis within a few weeks. The arterial echography/doppler
      and plethysmography patterns were suggestive of isolated small-to medium-size
      digital artery occlusions. An extensive search for an aetiology of digital
      necrosis, including complete tests of autoimmunity, remained negative. Two months
      later, despite alpha IFN withdrawal and intravenous infusions of ilomedin, the
      digital ischemia evolved to extensive necrosis that necessitated several
      amputations and a definitive spinal chord stimulation. Pathologic examination of
      arteries showed no vasculitis but diffuse arterial occlusions by thrombi.

PMID- 9161560
TI  - [Macroprolactinemia, a variety of hyperprolactinemia. Apropos of 5 cases].
AB  - Macroprolactinemia, due to increased circulating levels of large molecular weight
      forms of prolactin, results in elevated level of immuno-reactive prolactin. The
      big variants have only weak biological activity; thus macroprolactinemia appears
      as a case of hyperprolactinemia without clinical significance as demonstrated by
      the five patients described. The diagnosis is based upon chromatography which
      separates the hormone and its variants. This disorder produces a pitfall in the
      diagnostic evaluation of hyperprolactinemia.

PMID- 9161561
TI  - [Distal gangrene and cryoglobulinemia related to hepatitis C virus infection with
      presence of anticardiolipin antibodies].
AB  - We report the case of a 63-year old women with toe gangrene, peripheral
      polyneuropathy, polyarthritis, histologically proven necrotizing vasculitis, in
      association with type III mixed cryoglobulinemia and hepatitis C virus (HCV)
      infection. Raised anticardiolipin antibodies (aCL) were found, without beta 2
      glycoprotein I. HCV infection is associated with mixed cryoglobulinemia which can
      cause a vasculitis affecting various organs. The pathogenesis of production and
      clinical significance of aCL could be associated in this case with HCV infection.

PMID- 9161562
TI  - [Muscular metastases disclosing adenocarcinoma].
AB  - The authors report the case of a 67-year old man, with no particular medical
      history, presenting a large swelling of the left thigh. Investigations conclude
      to metastases located in muscles of the left thigh and of the pelvis, secondary
      to an adenocarcinoma of presumed pancreatic origin. With reference to this case,
      features of muscular metastases are reviewed. Muscular metastases seldom occur
      during the course of a cancer and are exceptionally the first manifestation of a
      neoplastic process. They are usually described as a painful mass, but symptoms
      can be misleading and delay diagnosis. Images obtained by ultrasonography,
      tomodensitometry and magnetic resonance imaging are not specific and histological
      examination is necessary to confirm the diagnosis.

PMID- 9161563
TI  - [The Cochrane Collaboration, support of therapeutic information].
AB  - Today, prescribers need to distinguish between the clinical practices based on
      randomized clinical trialing information and those based on animal physiological
      data or theory. Now the information on therapeutics is becoming more dense, more
      complex and less available to the clinicians. Information sources are numerous
      and varied, including data whose quality differs. These data are unhierarchised
      in terms of methodological quality and clinical relevance. It will be optimal if
      each prescriber could himself collect and analyse scientific information. In fact
      this situation cannot be effective in private physician's practices. An
      international collaboration, the Cochrane Collaboration, including volunteers,
      university researchers, and clinical investigators has the following objective:
      to prepare, maintain and disseminate systematic reviews of the effects of health
      care. The Cochrane Collaboration is thus the most adapted intermediairy between
      scientifically actualized data and clinical practitioners.

PMID- 9161564
TI  - [An echographic discovery].

PMID- 9161565
TI  - [Kikuchi syndrome, cytomegalovirus infection and lupus].

PMID- 9161566
TI  - [Pancytopenia caused by vitamin B12 deficiency: a case typical of of the
      Languedoc region...].

PMID- 9161567
TI  - [Scurvy disclosed by hematuria and large parietal and pelvic hematomas].

PMID- 9161568
TI  - [Biological autoimmune syndrome with antiphospholipid antibodies in occupational
      asbestosis].

PMID- 9161569
TI  - [Is it still necessary to search Koch bacillus in urine?].

PMID- 9161570
TI  - [Clinical symptomatology and prognosis of periarteritis nodosa in the elderly.
      Retrospective study of 25 periarteritis nodosa cases in young adults and 22 cases
      in aged patients].
AB  - Between 1985 and 1995, 47 patients with evidence of polyarteritis nodosa were
      seen at the department of Internal Medicine. Thirty-nine patients fulfilled
      histological and/or arteriographic diagnostic criteria, and in eight patients,
      the diagnosis was based on clinical criteria. At the onset of the disease, 25
      patients were below the age of 65 (group A) and 22 were above the age of 65
      (group B). Except for increased frequency of weight loss in group B and increased
      frequency of cutaneous signs (purpura and nodes) in group A, no significant
      differences were found in clinical and biological features. The mean duration of
      follow-up was 46.9 +/- 36.5 months. The number of deaths was significantly higher
      among the elderly (ten deaths in group B versus two in group A).

PMID- 9161571
TI  - [Main syndromes revealed in a consultation specially focusing on memory].
AB  - This paper reports our 2-year experience in a memory clinic practice at a
      University Hospital. During these 2 years, 128 patients with memory complaints
      were evaluated by a neurologist, a psychiatrist, a geriatrist and a
      neuropsychologist using a standardized test battery; only 58 of these patients
      actually presented with objective memory deficits. These memory impairments were
      mainly observed in patients with neurologic disorders (principally dementia) and
      in patients with psychiatric disorders (principally depression, major anxiety and
      psychiatric diseases with troubles of personality). The aim of this memory clinic
      is to identify the origin of memory disorders, provide a pharmacological
      treatment when required, propose appropriate assessment and follow up, and
      diagnose early symptoms of dementia.

PMID- 9161572
TI  - [Excessive daytime sleepiness].
AB  - When it is not due to an extrinsic origin, somnolence may be the main symptom of
      various diseases. Among these causes of excessive daytime sleepiness, obstructive
      sleep apnea syndrome is noteworthy for its very important prevalence, estimated
      at 4% in adult males. Due to repeated upper airway obstructions during sleep,
      this disease is efficiently treated by continuous positive airway pressure
      applied through a nasal masks during sleep. Another syndrome, periodic limb
      movements during sleep may also lead to a sleep fragmentation at the origin of
      daytime sleepiness. Its treatment is principally based on dopaminergic agonists.
      Narcolepsy-cataplexy and idiopathic hypersomnia are two causes of excessive
      daytime sleepiness in young people. The first is as frequent as multiple
      sclerosis and the second is ten times less frequent. The treatment of these two
      diseases is now based on a new French drug: modafinil(Modiodal). Sleep pathology
      still has only a small place in medical training. Excessive daytime sleepiness is
      therefore often misdiagnosed. In addition to their major risk of work or road
      accidents, numerous untreated patients continue to suffer from this very
      unpleasant symptom, at the origin of a major social handicap.

PMID- 9161573
TI  - [Environmental factors and iatrogenic elements in systemic scleroderma and
      related syndromes. Review of the literature].
AB  - The etiology of scleroderma remains unknown. Although a genetic susceptibility
      seems to play a role, some environmental and iatrogenic factors have been
      suggested to trigger the disease. Contact for many months or years with natural
      or synthetic "toxic" products (by inhalation, cutaneous contact, injection,
      swallowing or surgical implant) could be implicated in the development of typical
      scleroderma or pseudo-scleroderma. These products are either occupational or non
      occupational like those used at home in daily life. We will sum up the knowledges
      about this subject.

PMID- 9161574
TI  - [Sensorimotor polyneuropathy in a flare-up of Crohn disease].
AB  - A 22-year-old man developed an axonal sensorimotor polyneuropathy and an episode
      of pyloroduodenal stenosis at the same time. Rectal biopsy established the
      diagnosis of Crohn's disease. The etiologic investigations were negative. The
      neurological and gastrointestinal troubles improved and followed a parallel
      course. Without vitamin deficiency or metronidazole treatment, peripheral
      polyneuropathy is a rare event in Crohn's disease. An autoimmune cause is
      suspected.

PMID- 9161575
TI  - [Edwardsellia tarda septicemia in chronic lymphoid leukemia].
AB  - Edwardsiella tarda is a Gram negative bacilli. At least 300 cases have been
      reported in the literature. Here we report a new case of Edwardsiella tarda
      septicemia in an immunocompromised patient with chronic lymphocytic leukemia.
      Chief infections associated with this bacterium include bacterial gastroenteritis
      and septicemia with fatal evolution in 50% of cases. Risk factors associated with
      Edwardsiella tarda infections include exposure to aquatic environments and exotic
      animals. Although studies indicate that this bacterium is susceptible to most
      commonly prescribed antibiotics, it is interesting to note that in our case,
      Edwardsiella tarda was resistant to numerous beta-lactamins.

PMID- 9161576
TI  - [A nidulans bronchial aspergillosis after treatment of low-grade lymphoma with
      fludarabine].
AB  - Pulmonary aspergillosis is a common complication in neutropenic patients. The
      most important fungus is Aspergillus fumigatus. We report a case of invasive
      pulmonary aspergillosis due to Aspergillus nidulans secondary to fludarabine
      therapy. There are few cases of pulmonary aspergillosis due to Aspergillus
      nidulans (one chronic necrotizing pulmonary aspergillosis, one aspergilloma).
      Fludarabine induces a marked decreased of CD4 lymphocyte count responsible for
      opportunistic infections. It is the first case of aspergillosis after fludarabine
      therapy and the occurrence of such infection must be considered after purine
      analog therapy.

PMID- 9161577
TI  - [Large granular T-cell lymphocytic leukemia disclosed by bilateral uveitis:
      association with celiac disease].
AB  - A 70-year-old woman presented with bilateral anterior uveitis. She was on a
      gluten-free diet because of a celiac disease which had been diagnosed 3 months
      before. An anterior chamber aspirate contained a majority of large granular
      lymphocytes (LGL). The investigation of a chronic neutropenia led to the
      diagnosis of an otherwise typical T-LGL leukemia. This seems to be the first
      report of a CD3+ CD4- CD8+ T-LGL leukemia causing anterior uveitis through
      infiltration of leukemic cells, and the second report of an intriguing
      association of celiac disease with T-LGL leukemia.

PMID- 9161578
TI  - [Obstetrical complications of antiphospholipid syndrome].
AB  - Spontaneous miscarriages and fetal deaths take part of the definition of the
      antiphospholipid syndrome. Preeclampsia, fetal distress, preterm delivery,
      intrauterine growth retardation, mother's or newborn's vascular thrombosis are
      also included in the spectrum of clinical events linked to the antiphospholipid
      antibodies in pregnant women. The pathogenesis is not fully understood, but
      involves interactions between antibodies and phospholipidic molecules that are
      complexed to plasmatic proteins of the coagulation, or present on endothelial
      cell and platelet surfaces. The poor spontaneous prognosis of pregnancy in the
      context of the antiphospholipid syndrome is dramatically improved by preventive
      treatment. Therapeutic options are not codified and are various combinations of
      low-dose aspirin, heparin, steroids, intravenous immunoglobulins, and fish-oil
      derivatives. Excellent obstetrical care is mandatory in every case.

PMID- 9161579
TI  - [What should medical decision be based on?].
AB  - Medical decision making is basically related to three criteria: 1) estimated
      effectiveness in terms of objective and subjective results: 2) equity related to
      the concept of justice in the societal context; 3) legitimacy according to the
      willingness to pay of the society, its resource availability and the fraction of
      its income that is allowed to be spent for health care. A worsening dilemma is
      unescapable between a utilitarian medical project, and the traditional
      hippocratic rule of rescue no matter what the cost may be. Every care taker
      should be involved to give a clear account of medical decision in order to
      generate and adopt some acceptable view for a reliable implementation with
      respect to equity and justice.

PMID- 9161580
TI  - [Calcifications of the knee].

PMID- 9161581
TI  - [Campylobacter jejuni septicemia with cutaneous sites in a patient with human
      immunodeficiency virus infection].

PMID- 9161582
TI  - [Persistent polyclonal B-cell lymphocytosis with binucleated lymphocytes in a
      male patient].

PMID- 9161583
TI  - [Embolic infarction in the anterior cerebral artery in a patient with aneurysm of
      the interatrial septum].

PMID- 9161584
TI  - [Thrombospondin and platelet activation].

PMID- 9161585
TI  - Regional chemotherapy with blood filtration for non resectable liver metastases.

PMID- 9161586
TI  - Blunt abdominal trauma and severe pelvic rupture. What to do?
AB  - Severe pelvic injuries are often complicated by abdominal lesions. The main
      problem is excessive bleeding with threatening exsanguination. Bleeding
      originates mostly from the presacral venous plexus. By external fixation and
      reduction of the pelvic volume, the blood loss can be diminished or stopped.
      Laparotomy before external fixation will increase fracture dislocation and
      provoke further severe bleeding by loss of the tension band effect that the
      intact abdominal wall gives to the pelvis, protecting the latter against further
      symphysical diastasis.

PMID- 9161587
TI  - The splanchnic syndrome. Diagnosis and indications for treatment.
AB  - The typical chronic splanchnic syndrome is characterized by upper abdominal pain
      usually provoked by a meal, the finding of an epigastric bruit and weight loss in
      conjunction with haemodynamically significant stenosis of two or more of the
      splanchnic arteries. Diagnosis of chronic splanchnic syndrome depends mainly on a
      strong clinical suspicion. Usually the classical triad is incomplete or absent.
      Therefore chronic splanchnic syndrome should be considered, in every patient with
      chronic abdominal discomfort, after exclusion of other more common causes of
      upper abdominal discomfort. Findings from nonvasive and invasive diagnostic tests
      support the presence of chronic splanchnic syndrome. However, until now, the
      diagnosis of chronic splanchnic syndrome has usually only been made
      retrospectively if all the symptoms disappeared after technically successful
      reconstructive surgery. A variety of surgical techniques has been advocated to
      repair the splanchnic arteries. The choice of the technique is usually based on
      the preference and experience of the surgeon.

PMID- 9161588
TI  - The course of shipped livers used as full size, reduced or split grafts.
AB  - A total of 110 transplants, 66 in adults (8 retransplants) and 30 in children (6
      retransplants) were analysed according to the origin of the graft (shipped n = 39
      non-shipped i.e. self procured n = 71) and the way they were transplanted (as
      full size grafts (FS) n = 82, reduced size grafts (RED) n = 23 or split grafts
      (SG) n = 5). Twenty-nine transplants were performed for urgent and 81 for
      elective indications. There was a statistically higher incidence of 2 or more
      risk factors in the donors that were selfprocured (non shipped) than in donors
      from shipped livers (p = 0.025). The overall 3 months graft survival was 79.5%
      for shipped livers versus 69% for non-shipped livers and patients survival was
      89.2% versus 79.0% respectively after 3 months and 82.9% versus 74.4% after 40
      months. From these results that were analysed with risk factors of the donors,
      cold ischaemia time and liver function tests in recipients, transplanted for
      acute and elective indications, it is concluded that shipping of grafts is a
      practical and safe procedure even if size reduction or the use of SG is intended.

PMID- 9161589
TI  - An intermittently volvulating paraoesophageal hernia mimicking angina pectoris. A
      case report.
AB  - Paraoesophageal hernia is a type of hiatal hernia. The clinical signs are
      specific, different from those of the axial hernia. The diagnosis is often
      delayed. Once the diagnosis is made, surgical correction is mandatory. We present
      a new case of a patient with chest pain episodes who proved to have an
      intermittently volvulating paraoesophageal hernia.

PMID- 9161590
TI  - Laparoscopic repair of a Morgagni hernia.
AB  - The authors present a case of laparoscopic repair of a symptomatic Morgagni
      hernia in an adult patient. The indication for surgery was based on symptoms of
      dyspnea and sensation of thoracic tightness. A tension-free closure of the defect
      using a Marlex mesh was carried out. Recovery was quick and uneventful. One year
      after surgery, no complaints were noticed. Aetiology, diagnosis and treatment are
      discussed.

PMID- 9161591
TI  - Persistent left superior vena cava: transoesophageal echocardiographic findings
      and surgical strategies.
AB  - Two cases of casual discovery of persistent left superior vena cava during
      cardiac surgery are reported. Diagnoses were suspected at the time of
      peroperative transoesophageal echocardiography in the first case, and of
      preoperative fluoroscopy during a Swan-Ganz catheter insertion procedure in the
      second case. For both patients, a peroperative echo contrast study permitted to
      confirm the anomaly before initialization of cardiopulmonary bypass. Embryology,
      echocardiographic findings and surgical management, including cardioplegia
      delivering and left upper venous system drainage, are reviewed.

PMID- 9161592
TI  - Cystic adventitial disease of the popliteal vein: report of a case.
AB  - Cystic adventitial disease of the popliteal artery is a rare but classic cause of
      arterial insufficiency. We report a case in which the disease affected the
      popliteal vein, causing painless swelling of the left lower limb.

PMID- 9161593
TI  - Ruptured aneurysm of the profunda femoral artery associated with polyaneurysmal
      disease.
AB  - A 73-year-old man was admitted for rupture of an atherosclerotic aneurysm of the
      profunda femoris artery associated to popliteal and bilateral axillary arteries
      aneurysms. The aneurysm of the profunda femoris artery was developed between the
      branches of the crural nerves. Considering the patency of the superficial femoral
      artery and of the leg arterie, and to avoid injury to the crural nerve, no
      reconstruction of the profunda femoris was attempted. The aneurysm was ligated
      proximally and buttress sutures were placed on the site of rupture to achieve
      thrombosis of the aneurysms. Most of the published cases of aneurysm of the
      profunda femoris artery are false aneurysms developed after various trauma.
      Atherosclerotic aneurysm of the profunda femoris artery is a rare lesion and
      rupture is exceptional.

PMID- 9161594
TI  - Myasthenia gravis associated with thymolipoma: a case report.
AB  - A 31-year-old patient with a 2-year history of myasthenia gravis underwent
      resection of a mass in the anterior mediastinum. On histological examination, the
      tumour proved to be a thymolipoma. The association of thymolipoma with myasthenia
      gravis is rare. To our knowledge this is the 12th case reported. It is however
      the first in which histological examination revealed the presence of germinal
      centres. The tumour measured 28 x 14 x 2 cm and weighted 340 gr. This is by far
      the largest thymolipoma associated with myasthenia gravis reported. As in all
      previously published cases, the myasthenia associated symptoms improved
      significantly after surgery. In this case improvement occurred within weeks. In
      general, benefit after thymectomy is delayed until months to years.

PMID- 9161595
TI  - Alcohol, cytokines, and estrogen in the control of bone remodeling.
AB  - Alcohol has been identified as a risk factor for the development of osteoporosis.
      Chronic alcohol abuse has been shown to decrease bone mass and increase the
      incidence of fractures. Although the exact mechanism by which alcohol influences
      bone metabolism is not clear, it is likely a combination of both direct and
      indirect effects on bone cells. Alcohol has the potential to alter bone
      metabolism indirectly through its effects on gonadal hormones and through the
      secretion of cytokines shown to be critical factors in postmenopausal
      osteoporosis. Data are summarized here demonstrating that interleukin-1 and tumor
      necrosis factor play a direct causal role in the bone loss due to estrogen
      deficiency. In addition, studies are cited showing that these same cytokines are
      produced in alcohol-induced liver disease with the potential to enhance bone loss
      in post-menopausal women and in male patients. Although there are not yet data
      directly supporting the role of cytokines in bone loss due to alcohol
      consumption, the studies presented herein are intended to stimulate further
      research on the role of alcohol, estrogen, and cytokines in osteoporotic bone
      loss.

PMID- 9161596
TI  - Alcohol-induced bone disease: impact of ethanol on osteoblast proliferation.
AB  - The habitual consumption of even moderate quantities of alcohol (1 to 2
      drinks/day) is clearly linked with reduced bone mass (osteopenia). Biochemical
      and histological evaluation of patients with alcoholic bone disease reveal a
      marked impairment in bone formation in the face of relatively normal bone
      resorption. Experiments using well-defined osteoblastic model systems indicate
      that the observed reductions in bone formation result from a direct,
      antiproliferative effect of ethanol on the osteoblast itself. As bone remodeling
      and mineralization are dependent on osteoblasts, it follows that the deleterious
      effect of alcohol on these cells would result in slowed bone formation, aberrant
      remodeling of skeletal tissue and, ultimately, osteopenia and fractures. The
      skeletal consequences of alcohol intake during adolescence, when the rapid
      skeletal growth ultimately responsible for achieving peak bone mass is occurring,
      may be especially harmful. The specific subcellular mechanisms whereby ethanol
      inhibits cell proliferation are, as yet, unknown. During the last few years,
      attention has shifted from nonspecific membrane perturbation effects to actions
      on certain signaling proteins. Specifically, there is increasing evidence that
      ethanol may exert significant effects on transmembrane signal transduction
      processes that constitute major branches of cellular control mechanisms. At
      present, abstinence is the only effective therapy for alcohol-induced bone
      disease. An improved understanding of the pathogenesis of alcohol-induced bone
      disease may eventually result in alternative therapeutic avenues for those who
      are unable to abstain.

PMID- 9161597
TI  - Alcohol, osteoporosis, and bone regulating hormones.
AB  - The mechanism of the production of ethanol-associated osteopenia seems to be a
      direct effect of alcohol on bone cells and an indirect or modulating effect
      through mineral regulating hormones such as vitamin D metabolites, parathyroid
      hormone, and calcitonin. The modulating effects of these hormones on bone and
      mineral metabolism in acute and chronic alcohol consumption is discussed herein.

PMID- 9161598
TI  - Ethanol's inhibition of LTP may not be mediated solely via direct effects on the
      NMDA receptor.
AB  - Acute abuse of alcohol is well known to have deleterious effects on memory.
      However, the molecular and cellular bases of this effect are not well understood.
      Ethanol is known to inhibit long-term potentiation (LTP), a putative cellular
      substrate of memory. However, there is controversy concerning the doses of
      ethanol required for inhibition of LTP. We examined the doses of ethanol required
      to inhibit LTP in the CA1 region of the hippocampus. We used two different LTP
      inducing paradigms in these studies and found that only doses of ethanol
      associated with profound intoxication (50-100 mM) can produce significant
      inhibition of LTP. We also investigated the molecular mechanisms of ethanol's
      effect on LTP. Activation of the N-methyl-D-aspartate receptor plays a critical
      role in LTP, and ethanol has been shown to partially inhibit N-methyl-D-aspartate
      receptor function. We tested directly whether the level of N-methyl-D-aspartate
      inhibition produced by 100 mM ethanol is sufficient to account for the complete
      inhibition of LTP produced by 100 mM ethanol. Our data suggest that ethanol's
      effects on the N-methyl-D-aspartate receptor can account for most, but not all of
      ethanol's inhibition of LTP.

PMID- 9161599
TI  - Effects of dihydropyridines on the components of the ethanol withdrawal syndrome:
      possible evidence for involvement of potassium, as well as calcium?
AB  - Comparison was made of the ability of two dihydropyridine calcium channel
      antagonists, nitrendipine and felodipine, to prevent a range of signs of ethanol
      withdrawal. The increases in handling-induced behavior seen in mice during
      withdrawal from chronic ethanol treatment were prevented by administration of
      nitrendipine, 50 mg/kg, but not by, felodipine, 10 mg/kg, a dose that caused a
      similar displacement of dihydropyridine binding in central nervous system tissue,
      in vivo and in vitro. A higher dose of felodipine, 20 mg/kg, also had no effects.
      Nitrendipine, but not felodipine, prevented audiogenic seizures during the
      withdrawal phase. Similarly, nitrendipine prevented both the decrease in
      thresholds for N-methyl-DL-aspartate seizures and the increase in thresholds for
      convulsions due to 4-aminopyridine, which were seen during the withdrawal period,
      while felodipine did not alter either of these changes. Withdrawal from the
      ethanol chronic treatment increased the thresholds to seizures produced by
      intravenous aminophylline; this change was also prevented by nitrendipine. The
      significance of this increase in thresholds was lost after felodipine
      administration. In naive mice (not treated with ethanol) the doses of
      nitrendipine and felodipine used in the withdrawal studies were tested against
      the effects of convulsant drugs. Both dihydropyridines increased, to similar
      extents, the thresholds for seizures produced by bicuculline, pentylenetetrazol,
      and by N-methyl-DL-aspartate. The thresholds for aminophylline were unaltered by
      either dihydropyridine. In contrast, the thresholds for seizures due to 4
      aminopyridine in the naive animals were not changed by felodipine, but were
      increased by nitrendipine. The results suggest that changes in potassium, as well
      as calcium, may possibly be involved in some of the stages of the ethanol
      withdrawal syndrome.

PMID- 9161600
TI  - Effect of ethanol on gastric mucus glycoprotein synthesis, translocation,
      transport, glycosylation, and secretion.
AB  - The effect of ethanol on mucus glycoprotein synthesis, intracellular
      modification, transport, glycosylation, and secretion was studied in rat gastric
      mucous cells. Preincubation of the in vitro translation mixture containing
      gastric mucous cells mRNA for 60 min with 0 to 120 mM ethanol caused a decrease
      in the synthesis of mucus glycoprotein apopeptide by up to 40%. The reduction in
      translation was time- and ethanol concentration-dependent. After 60 min,
      translation in the presence of 30, 60, and 120 mM ethanol decreased to 83.3 +/-
      2.3%, 75.5 +/- 0.4%, and 63.6 +/- 2.6%, respectively. The experiments conducted
      with endoplasmic reticulum microsomes, preincubated with ethanol, and used in the
      studies of cotranslational translocation of the apomucin showed a 20% decrease in
      the transfer of mucus glycoprotein apopeptide to the lumen of endoplasmic
      reticulum microsomes. In the presence of ethanol, processing of mucus
      glycoprotein apopeptide in Golgi was also inhibited. During the initial 30 min of
      incubation with 0 to 120 mM ethanol, glycosylation seemed to proceed at the same
      rate in the samples with and without ethanol. However, during consecutive 30 min
      of incubation, glycosylation in the presence of 60 mM ethanol decreased by 30 to
      35%, and with 120 mM ethanol was completely inhibited. Measurements of the effect
      of ethanol on the discharge of mucus glycoprotein from the intracellular stores
      revealed that, on average, the secretory output of the rat gastric mucosa exposed
      to ethanol liquid diet for 8 weeks decreased by 77% or more, and adherence of the
      glycoprotein to the gastric epithelium was weakened. Results indicate that
      ethanol inhibits synthesis, transport, and processing of gastric mucus
      glycoprotein, and that the processes taking place in different intracellular
      compartments contribute in the additive fashion and, are reflected in a dramatic
      decrease in the delivery of mucus glycoprotein to the gastric epithelial
      surfaces.

PMID- 9161601
TI  - Prenatal alcohol exposure results in hyperactivity of the hypothalamic-pituitary
      adrenal axis of the offspring: modulation by fostering at birth and postnatal
      handling.
AB  - Exposure of fetal rats to alcohol results in permanent hyperactivity of the
      hypothalamic-pituitary-adrenal (HPA) axis. In contrast, postnatal handling or
      fostering have been reported to restrain HPA activity. Because of the deleterious
      consequences of a hyperresponsive HPA axis, we thought that the possibility that
      postnatal manipulations might be able to reverse the influence of prenatal
      alcohol treatment deserved investigation. To test this hypothesis, we exposed rat
      dams to alcohol by inhalation during the second week of gestation. At birth, pups
      were either fostered or remained with their dam. For the first 3 weeks, litters
      were handled daily for 15 min or left undisturbed. At 22 days of age, male and
      female pups were decapitated under basal conditions, after 10 min of mild electro
      footshock, or 10 min after footshock had been terminated. As expected, prenatal
      exposure to alcohol induced increased adrenocorticotropin (ACTH) secretion in
      response to footshock, and postnatal handling of control pups resulted in a
      suppression of corticosterone and ACTH release, although changes in this latter
      hormone did not reach statistical significance. Surprisingly, however, pups
      exposed to alcohol that were also fostered and handled after birth, showed an
      ACTH response to footshock stress that was significantly larger than all other
      groups. This unexpected response may be due to alterations in maternal-pup
      behaviors and may indicate that these manipulations act on different neuronal
      substrates within the central HPA of young rats. Further studies are needed to
      determine whether adrenal regulation is also altered in animals exposed to
      alcohol prenatally and reared in a similar manner.

PMID- 9161602
TI  - Human GABAA receptor alpha 1 and alpha 3 subunits genes and alcoholism.
AB  - gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the
      brain. GABA effects are largely mediated by binding to the postsynaptic GABAA
      receptor, causing the opening of an integral chloride-ion channel. The GABAA
      antagonists picrotoxin and bicuculline reduce some ethanol-induced behaviors,
      such as motor impairment, sedation, and hypnosis. The role of this receptor in
      alcoholism is further supported by effective alleviation of alcohol withdrawal
      symptoms by GABAA agonists. To determine the role of the GABAA receptor (GABR)
      genes in the development of alcoholism, we have used alpha 1 and alpha 3 simple
      sequence repeat polymorphisms in a sample of unrelated alcoholics, alcoholic
      probands with both parents, and psychiatrically normal controls. For the GABR
      alpha 1 gene, the differences between allele frequencies, when all alleles were
      compared together, were not significant between total alcoholics, subtypes of
      alcoholics, and normal controls. However, for GABR alpha 3, the differences
      between total alcoholics and normal controls were significant when all alleles
      were compared together. The differences between subtypes of alcoholics and normal
      controls were not significant. The results of haplotype relative risk analysis
      for both genes, GABR alpha 1 and GABR alpha 3, were also negative. It is possible
      that the sample size in the haplotype relative risk is too small to have power to
      detect the differences in transmitted versus nontransmitted alleles. There is a
      need for a replication study in a large family sample that will allow haplotype
      relative risk or affected sib-pair analysis.

PMID- 9161603
TI  - Cortical and subcortical white matter damage without Wernicke's encephalopathy
      after recovery from thiamine deficiency in the rat.
AB  - The relative etiologic roles of ethanol and thiamine deficiency in the cortical
      atrophy and loss of cerebral white matter in chronic alcoholics are uncertain.
      The present study examined the distribution of degenerating axons within cortical
      and subcortical tracts 1 week after recovery from early to late symptomatic
      stages of thiamine deficiency in the absence of ethanol in Sprague-Dawley rats.
      The brains of rats exposed to an early symptomatic stage of pyrithiamine-induced
      thiamine deficiency, 12-13 days of treatment, contained degenerating axons in
      corpus callosum, anterior commissure, external and internal capsules, optic and
      olfactory tracts, and fornix and mammillothalamic tracts. A dense pattern of
      degenerating axons was evident in layers III-IV of frontal and parietal cortex.
      Less intense and more evenly distributed degenerating axons were present in
      layers IV-VI of frontal, parietal, cingulate, temporal, retrosplenial, occipital,
      and granular insular cortex. Neuronal counts in mammillary body nuclei and areal
      measurements of the mammillary body were unchanged from controls and the thalamus
      was relatively undamaged. In animals reversed at later and more advanced
      symptomatic stages of thiamine deficiency, 14-15 days of treatment, degenerating
      axons were found in other cortical regions and hippocampus and there was
      extensive neuronal loss and gliosis within mammillary body and medial thalamus.
      These results demonstrate that a single episode of thiamine deficiency can
      selectively damage cortical white matter tracts while sparing the thalamus and
      mammillary body and may be a critical factor responsible for the pathological and
      behavioral changes observed in alcoholics without Wernicke's encephalopathy.

PMID- 9161604
TI  - Ethanol, flunitrazepam, and pentobarbital modulation of GABAA receptors expressed
      in mammalian cells and Xenopus oocytes.
AB  - GABAA receptors composed of human alpha 1 beta 2 gamma 2L, alpha 1 beta 2 gamma
      2S, alpha 1 beta 3 gamma 2S, alpha 6 beta 3 gamma 2S, and alpha 5 beta 3 gamma 3
      subunits as well as bovine alpha 1 beta 1 gamma 2L and alpha 1 beta 1 subunits
      were stably expressed in mammalian L(tk-) cells and transiently expressed in
      Xenopus oocytes. Effects of muscimol, ethanol, flunitrazepam, and pentobarbital
      on receptor function were compared for the two expression systems using a 36Cl-
      flux assay for cells and an electrophysiological assay for oocytes. Muscimol
      activated all receptors in both expression systems but was more potent for L(tk-)
      cells than oocytes; this difference ranged from 2.6-to 26-fold, depending upon
      subunit composition. The most pronounced differences between receptors and
      expression systems were found for ethanol. In L(tk-) cells, low (5-50 mM)
      concentrations of ethanol potentiated muscimol responses only with receptors
      containing the gamma 2L subunit. In oocytes, concentrations of 30-100 mM produced
      small enhancements for most subunit combinations. Flunitrazepam enhanced muscimol
      responses for all receptors except alpha 6 beta 3 gamma 2S and alpha 1 beta 1,
      and this enhancement was similar for both expression systems. Pentobarbital also
      enhanced muscimol responses for all receptors, and this enhancement was similar
      for L(tk-) cells and oocytes, except for alpha 6 beta 3 gamma 2S where the
      pentobarbital enhancement was much greater in oocytes than cells. The alpha 6
      beta 3 gamma 2S receptors were also distinct in that pentobarbital produced
      direct activation of chloride channels in both expression systems. Thus, the type
      of expression/assay system markedly affects the actions of ethanol on GABAA
      receptors and also influences the actions of muscimol and pentobarbital on this
      receptor. Differences between these expression systems may reflect
      posttranslational modifications of receptor subunits.

PMID- 9161605
TI  - Effects of maternal ethanol consumption and buspirone treatment on dopamine and
      norepinephrine reuptake sites and D1 receptors in offspring.
AB  - Previously, it was shown that in utero ethanol exposure results in decreased
      serotonin (5-HT) and altered concentrations of 5-HT reuptake sites and 5-HT1A
      receptors in fetal and/or postnatal rats. Because fetal 5-HT is an essential
      trophic factor, this laboratory previously investigated the hypotheses that the
      early ethanol-associated 5-HT deficit contributed to subsequent development
      abnormalities in the serotonergic system and that the effects of the fetal 5-HT
      deficit could be prevented by maternal treatment with buspirone, a 5-HT1A
      receptor agonist. The present report determined the effects of maternal treatment
      with buspirone on two other neurotransmitter systems in the developing offspring
      of ethanol-fed dams: dopamine (DA) and norepinephrine reuptake sites and D1
      receptors in postnatal day 19 offspring of control and ethanol-fed dams, that
      received daily injections of saline or 4.5 mg/kg buspirone. These investigations
      found that in utero ethanol exposure significantly decreased norepinephrine
      reuptake sites in the dorsomedial hypothalamic nucleus and anteroventral thalamic
      nucleus. There was also an ethanol effect in the dorsal raphe. D1 receptors were
      moderately increased (5-10% increase) in the striatum, and DA reuptake sites were
      unchanged in PN19 ethanol-exposed offspring. No other significant ethanol-related
      effects were noted. Maternal buspirone treatment did not adversely affect the
      concentration of DA reuptake sites or D1 receptors in control rats. Thus, whereas
      buspirone exerts protective effects on the developing 5-HT system of ethanol
      exposed rats, it does not appear to damage the development of the DA system.
      Maternal buspirone produced only one significant abnormality in control
      offspring; it resulted in significant reduction of norepinephrine reuptake sites
      in the DR.

PMID- 9161606
TI  - Ethanol differentially affects metabolic and mitotic processes in chick embryonic
      cells.
AB  - Our laboratory has been investigating the mechanisms by which ethanol-induced
      growth inhibition occurs in a developing embryo, and our studies have focused on
      disruption of cellular signaling pathways. Previous work on ethanol-induced
      changes in signaling systems that regulate ornithine decarboxylase activity
      indicated that the pathways containing protein kinase A, protein kinase C (PKC),
      and insulin-dependent tyrosine kinase were important for the control of ornithine
      decarboxylase in chick embryonic cells. Herein, we report ethanol's effect on the
      regulation of glucose uptake and thymidine uptake by these same kinase pathways.
      A pronounced increase in glucose uptake was associated with PKC downregulation in
      both vehicle- and ethanol-exposed cells, with the larger increase occurring in
      ethanol-exposed cells. An increase in thymidine uptake was associated with an
      activation of all three kinases, as well as with downregulation of PKC. Because
      previous work on signaling pathways has looked for changes in the insulin
      signaling pathway, the work herein focuses on the signaling pathways involving
      protein kinase A and PKC. cAMP levels were increased by ethanol treatment, but
      the increase was relatively small. Analysis of changes in PKC activity induced by
      ethanol exposure showed a significant suppression of PKC activity in the ethanol
      treated cells and suggested that, overall, ethanol treatment affects the
      regulation of glucose uptake in embryonic cells predominantly by PKC
      downregulation.

PMID- 9161607
TI  - Effect of three different modes of alcohol administration on the activity of the
      rat hypothalamic-pituitary-adrenal axis.
AB  - The present study compared the effect of different modes of alcohol
      administration on the activity of the hypothalamic-pituitary-adrenal (HPA) axis.
      In a first series of studies, we investigated the influence of the
      intraperitoneal (ip) and intragastric (ig) effect of acutely administered
      alcohol. Over a 3-hr period, alcohol induced dose-related increases in
      adrenocorticotropic hormone (ACTH) and alcohol levels in the circulation. There
      was a good correlation between blood ACTH and alcohol levels (ip treatment, R =
      0.84; ig treatment, R = 0.79). Measurement of steady-state mRNA of the immediate
      early gene NGFI-B, taken as an index of neuronal activation in the
      paraventricular nucleus (PVN) of the hypothalamus of rats administered 3 g of
      alcohol/kg, indicated significant (p < 0.01) increases between 60 and 180 min
      after both ip and ig alcohol injection, with peak stimulation at 1 and 2 hr,
      respectively. Although NGFI-B mRNA levels had returned to control level in the
      parvicellular portion of the PVN of animals administered the drug ip 4 hr
      earlier, they were still significantly (p < 0.01) elevated 4 hr after ig
      treatment. A second series of studies used rats fed an alcohol diet containing
      6.4% alcohol (w/v), or pair-fed. The rats were tested during the 4th or 6th night
      of treatment. Despite blood alcohol levels ranging between 0.060 and 0.140% w/v,
      there was no significant rise in plasma ACTH/corticosterone levels in animals fed
      the drug, and no detectable NGFI-B mRNA in their PVN. Collectively, these results
      indicate that both the ip and the ig acute injection of alcohol induced dose
      related increases in plasma ACTH levels. PVN neuronal activation was also
      observed. In contrast, the alcohol diet had no effect on HPA hormone levels or
      PVN expression of NGFI-B.

PMID- 9161608
TI  - Forskolin delays the ethanol-induced desensitization of hypothalamic beta
      endorphin neurons in primary cultures.
AB  - Ethanol and its metabolite acetaldehyde have been shown to stimulate
      immunoreactive beta-endorphin (IR-beta-EP) secretion from hypothalamic neurons in
      primary cultures. Also, chronic ethanol and acetal-dehyde have been shown to
      cause the development of tolerance and desensitization of these neurons. In this
      study, we determined some of the cellular events leading to desensitization of
      the function of beta-endorphin (beta-EP) secretory neurons. The fetal
      hypothalamic cells were treated with various doses of ethanol (25 and 50 mM) or
      acetaldehyde (6.25, 12.5, and 25 mM) for 6 hr or treated with these drugs at 12
      hr intervals for 72 hr. Determination of IR-beta-EP concentrations in the media
      revealed that ethanol increased IR-beta-EP secretion from these cultures for 12
      hr, after this period, the cultured cells did not respond to ethanol.
      Acetaldehyde stimulated IR-beta-EP secretion from this culture for a period of 48
      hr, but the IR-beta-EP secretory response to acetaldehyde reduced gradually with
      time during the first 48-hr period and reached the basal level at 72 hr. The
      desensitization of beta-EP neurons 12 hr after treatment with alcohol did not
      seem to be related to the loss of viable cells, because chronic ethanol exposures
      did not produce any effect on cell viability. However, reduced IR- beta-EP
      secretory response to acetaldehyde with time was associated with the time
      dependent increase in cell death. Pretreatment of cultures with a cAMP analog,
      forskolin, increased the activity of functional beta-EP neurons and delayed the
      ethanol desensitization effects on these neurons. Pretreatment of forskolin did
      not delay the acetaldehyde desensitization of beta-EP neurons, but protected
      these cells from acetaldehyde toxicity. These results suggest that (i) chronic
      treatment with ethanol desensitizes beta-EP-secreting neurons due to reduced
      cellular functions and (ii) chronic acetaldehyde reduces beta-EP
      neurotransmission due to cell death. Furthermore, data suggest for the first time
      that cAMP pretreatments delay the ethanol-induced desensitization of opioid
      neurons and partly protect against the neurotoxic action of acetaldehyde on
      opioid neurons.

PMID- 9161609
TI  - The nitric oxide synthase inhibitor L-NAME (N omega-nitro-L-arginine methyl
      ester) does not produce discriminative stimulus effects similar to ethanol.
AB  - N-methyl-D-aspartate (NMDA) antagonists substitute for the discriminative
      stimulus effects of ethanol, indicating that a component of ethanol's behavioral
      activity is produced via blockade of NMDA receptor/channel function. Recently, it
      has been reported that ethanol inhibits NMDA-stimulated nitric oxide synthase
      (NOS) activity in cortical neurons, thereby decreasing the formation of nitric
      oxide (NO) in the brain. These findings suggest that some of the behavioral
      effects of ethanol may be mediated by inactivation of NOS. The present study
      examined the role of NO formation in mediating the discriminative stimulus
      effects of ethanol. To address this hypothesis, an NOS inhibitor, N omega-nitro-L
      arginine methyl ester (L-NAME) and an NMDA competitive antagonist, (D)-4-(3
      phosphonoprop-2-enyl) piperazine-2-carboxylic acid (CPPene), were administered to
      two groups of rats trained to discriminate 1.5 g/kg of ethanol (n = 6) or 2.0
      g/kg (n = 7) of ethanol from water. After training, dose ranges of CPPene (3 to
      17 mg/kg, ip) and L-NAME (100 to 780 mg/kg, ip) were tested for ethanol-like
      effects. L-NAME was also tested under a range of pretreatment times (20, 60, 90,
      and 120 min). An additional group of rats trained to discriminate 2.0 g/kg (n =
      7) of ethanol from water was also tested with CPPene (10 mg/kg, ip) and L-NAME
      (100 and 300 mg/kg, ip) to verify data gathered from the original 2.0 g/kg of
      ethanol group tested with L-NAME after a 20-minute pretreatment. Although
      overall, 17 of 20 animals trained to discriminate ethanol from water exhibited
      complete substitution of CPPene for ethanol, L-NAME, without affecting response
      rates, did not consistently substitute for either 1.5 g/kg or 2.0 g/kg of
      ethanol. These results indicate that inhibition of NO formation is less effective
      than direct NMDA receptor antagonism in producing ethanol-like discriminative
      stimulus effects.

PMID- 9161610
TI  - Characteristics of alcohol dehydrogenases of certain aerobic bacteria
      representing human colonic flora.
AB  - We have recently proposed the existence of a bacteriocolonic pathway for ethanol
      oxidation [i.e., ethanol is oxidized by alcohol dehydrogenases (ADHs) of
      intestinal bacteria resulting in high intracolonic levels of reactive and toxic
      acetaldehyde]. The aim of this in vitro study was to characterize further ADH
      activity of some aerobic bacteria, representing the normal human colonic flora.
      These bacteria were earlier shown to possess high cytosolic ADH activities
      (Escherichia coli IH 133369, Klebsiella pneumoniae IH 35385, Klebsiella oxytoca
      IH 35339, Pseudomonas aeruginosa IH 35342, and Hafnia alvei IH 53227). ADHs of
      the tested bacteria strongly preferred NAD as a cofactor. Marked ADH activities
      were found in all bacteria, even at low ethanol concentrations (1.5 mM) that may
      occur in the colon due to bacterial fermentation. The Km for ethanol varied from
      29.9 mM for K. pneumoniae to 0.06 mM for Hafnia alvei. The inhibition of ADH by 4
      methylpyrazole was found to be of the competitive type in 4 of 5 bacteria, and Ki
      varied from 18.26 +/- 3.3 mM for Escherichia coli to 0.47 +/- 0.13 mM for K.
      pneumoniae. At pH 7.4, ADH activity was significantly lower than at pH 9.6 in
      four bacterial strains. ADH of K. oxytoca, however, showed almost equal
      activities at neutral pH and at 9.6. In conclusion, NAD-linked alcohol
      dehydrogenases of aerobic colonic bacteria possess low apparent Km's for ethanol.
      Accordingly, they may oxidize moderate amounts of ethanol ingested during social
      drinking with nearly maximal velocity. This may result in the marked production
      of intracolonic acetaldehyde. Kinetic characteristics of the bacterial enzymes
      may enable some of them to produce acetaldehyde even from endogenous ethanol
      formed by other bacteria via alcoholic fermentation. The microbial ADHs were
      inhibited by 4-methylpyrazole by the same competitive inhibition as hepatic ADH,
      however, with nearly 1000 times lower susceptibility. Individual variations in
      human colonic flora may thus contribute to the risk of alcohol-related
      gastrointestinal morbidity, such as diarrhea, colon polyps and cancer, and liver
      injury.

PMID- 9161611
TI  - Hearing, speech, language, and vestibular disorders in the fetal alcohol
      syndrome: a literature review.
AB  - Fetal alcohol syndrome (FAS) is characterized in part by mental impairment, as
      well as craniofacial and ocular anomalies. These conditions are traditionally
      associated with childhood hearing disorders, because they all have a common
      embryonic origin in malformations of the first and second branchial arches, and
      have similar critical periods of vulnerability to toxic insult. A review of human
      and animal research indicates that there are four types of hearing disorders
      associated with FAS. These are: (1) a developmental delay in auditory maturation,
      (2) sensorineural hearing loss, (3) intermittent conductive hearing loss due to
      recurrent serous otitis media, and (4) central hearing loss. The auditory and
      vestibular systems share the same peripheral apparatuses (the inner ear and
      eighth cranial nerve) and are embryologically and structurally similar.
      Consequently, vestibular disorders in FAS children might be expected. The
      evidence for vestibular dysfunction in FAS is ambiguous, however. Like other
      syndromes associated with craniofacial anomalies, hearing disorders, and mental
      impairment, FAS is also characterized by a high prevalence of speech and language
      pathology. Hearing disorders are a form of sensory deprivation. If present during
      early childhood, they can result in permanent hearing, language, and mental
      impairment. Early identification and intervention to treat hearing, language, and
      speech disorders could therefore result in improved outcome for the FAS child.
      Specific recommendations are made for intervention and future research.

PMID- 9161612
TI  - Personality and substance use disorders: I. Effects of gender and alcoholism
      subtype.
AB  - The relationship between alcoholism and self-rated personality was explored in a
      community-ascertained sample of 303 male and 103 female alcoholics, and 304 male
      and 770 female nonalcoholics. Alcoholics met DSM-III-R lifetime criteria for
      alcohol dependence; personality was assessed using the Multidimensional
      Personality Questionnaire. Compared with controls, alcoholics scored
      significantly higher on all indicators of negative emotionality, and consistently
      lower on all indicators of constraint. Individual effect sizes were moderate in
      both the male and female samples. A subsample of severe male alcoholics,
      identified by cluster analysis, was characterized by relatively early onset of
      problem drinking and relatively high antisociality and familial loading of
      problem drinking; they were also more extreme than moderate male alcoholics on
      negative emotionality and constraint. When taken in aggregate, personality risk
      appears to be associated with a continuum of alcoholic risk such that individuals
      extreme in both negative emotionality and behavioral disinhibition have
      especially high rates of alcoholism.

PMID- 9161613
TI  - Frontal lobe volume loss observed with magnetic resonance imaging in older
      chronic alcoholics.
AB  - This study used magnetic resonance imaging to quantify the extent and pattern of
      tissue volume deficit and cerebrospinal fluid volume enlargement in younger
      versus older chronic alcoholics relative to normal controls. In the present
      analysis, we divided our previously reported group of 62 alcoholic men into a
      younger group (n = 33, age mean = 37.5 +/- 4.5, and range = 26 to 44 years) and
      an older group (n = 29, age mean = 52.7 +/- 6.0, and range = 45 to 63 years) to
      examine whether, in addition to extent, the two age groups differed in pattern of
      tissue type and regional brain volume abnormalities quantified with magnetic
      resonance imaging. Brain volumes were adjusted for normal variation in head size
      and age established from a group of healthy controls and were expressed as Z
      scores. The younger group had significant cortical gray, but not white, matter
      volume deficits and sulcal and ventricular enlargement relative to age-matched
      controls. The older group had volume deficits in both cortical gray and white
      matter and sulcal and ventricular enlargement that significantly exceeded the
      younger alcoholic group. An analysis of six cortical regions revealed that,
      although both age groups had gray matter volume deficits throughout the cortex,
      the older alcoholic group had a selectively more severe deficit in prefrontal
      gray matter relative to the younger alcoholic group. Similarly, the cortical
      white matter volume deficit in the older alcoholics was especially severe in the
      prefrontal and frontal regions. The differences in brain dysmorphology between
      the two alcoholic groups cannot easily be attributed to potential alcohol history
      differences typically related to age because the two groups had similar disease
      durations and amounts of lifetime alcohol consumption. These results provide in
      vivo evidence that the frontal lobes are especially vulnerable to chronic
      alcoholism in older men.

PMID- 9161614
TI  - Subject-collateral reports of drinking in inpatient alcoholics with comorbid
      mental disorders.
AB  - Verbal self-report continues to be the primary method by which clinicians and
      researchers obtain measurements of a person's past drinking. In addition,
      collateral reports are an important second measure of an individual's drinking
      behavior. Although there is considerable confidence in the use of collateral
      reports as a measure of drinking in individuals with only a diagnosis of alcohol
      abuse or dependence, information about subject-collateral reports for alcoholics
      with a comorbid mental disorder is lacking. given both that symptoms of mental
      illness can negatively impact cognitive processes relevant to the recall of
      information, and that such symptoms can be influenced by alcohol consumption, it
      is important to be confident in the reports of alcohol use in dually diagnosed
      individuals. This study examined subject-collateral reports of alcohol use in two
      groups of inpatient alcoholics: those meeting DSM-III-R criteria for an alcohol
      use disorder and a current mental disorder (n = 91) and those meeting criteria
      for an alcohol use disorder only (n = 93). Overall, the results show that the
      self-reports of alcoholics with comorbid mental disorders are generally valid. In
      addition, subject-collateral agreement was found to be similar for both groups,
      with no consistent tendency to overreport or underreport alcohol or drug use in
      either group. Importantly, psychological symptom severity and cognitive
      functioning were not related to subject-collateral agreement. However, less
      frequent contact between subject and collateral had a more negative impact on
      subject-collateral agreement for the dual diagnosis group, compared with the
      alcohol-only group. Recommendations for enhancing the accuracy of self-reports of
      drinking in a dual diagnosis population are discussed.

PMID- 9161615
TI  - Association between alcohol use and smoking in adolescent and young adult twins:
      a bivariate genetic analysis.
AB  - The association between alcohol use and smoking was examined in a large
      population-based sample of Dutch twins consisting of three age groups; young
      adolescent twins aged 12-14 years (n = 650 twin pairs), 15-16-years-old
      adolescent twins (n = 705 twin pairs), and young adult twins aged 17-25 years (n
      = 1266 twin pairs). For all three age groups, alcohol use and smoking were
      correlated (r = 0.5-0.6). Adolescents and young adults who smoked were more
      likely to drink alcohol than nonsmokers. The relation between alcohol use and
      smoking was also found within a twin pair; alcohol use in one twin was correlated
      with smoking in the cotwin. This finding suggested that familial factors
      contribute to the association between alcohol and tobacco use. With a bivariate
      genetic model, it was examined to what extent the comorbidity was due to genetic
      and environmental factors that predispose to both alcohol use and smoking. The
      genetic analyses showed that the underlying factors that influence alcohol and
      tobacco use and cause their association were different for adolescent and young
      adult twins. Initiation of alcohol use and smoking in adolescents (aged 12-16
      years) was substantially influenced by the same shared environmental features.
      Alcohol and tobacco use in young adults were associated due to the same genetic
      risk factors.

PMID- 9161616
TI  - Marital functioning in early versus late-onset alcoholic couples.
AB  - Current knowledge about alcohol and marital functioning is limited by restrictive
      sample selection, inattention to the literature on individual-based alcoholic
      subtypes, and lack of research linking individual differences among alcoholics to
      marital functioning. The present study was designed to study marital functioning
      of alcoholics in light of current alcohol typologies. Subjects were part of a
      larger study on conjoint treatment of alcoholic males and their female partners.
      Four typologies-including Type 1/2, In-Home/Out-of-home, Steady/Episodic, and
      Early/Late Onset-were tested for replicability and discriminant validity before
      linking them to marital functioning. Discriminant validity was found only for the
      Early (59%)-versus Late (41%)-Onset typology;thus, further analyses linked only
      this typology with marital functioning. At baseline, Early-Onset couples reported
      more marital instability, and the females in these couples were more distressed.
      During treatment, Early-Onset couples reported higher daily marital satisfaction
      than Late-Onset couples. Regardless of age of onset, males reported higher
      marital satisfaction than their spouses during treatment, but their satisfaction
      did not increase during treatment. Female partners' marital satisfaction
      increased during treatment. Female partners of Late-Onset males reported
      particularly low marital satisfaction during treatment. Parsing the sample
      according to the early-/late-onset typology yielded different predictors of
      marital satisfaction for males and females within each subtype. For female
      partners of Early-Onset alcoholics, psychological distress unrelated to her
      partner's drinking severity was most associated with her own marital
      satisfaction, whereas marital adjustment of female partners of Late-Onset
      alcoholics was most associated with the male's level of perceptual accuracy
      regarding her needs. This pattern was reversed for the males; marital adjustment
      of Early-Onset alcoholics was most associated with his partner's perceptual
      accuracy of his needs, whereas marital functioning of Late-Onset alcoholics was
      best accounted for by his own psychological distress.

PMID- 9161617
TI  - Alcohol expectancies and drinking characteristics in parents of children with
      attention deficit hyperactivity disorder.
AB  - Alcohol expectancies, drinking characteristics, and their association were
      examined in 587 adults: 431 parents of children with attention deficit
      hyperactivity disorder (ADHD) and 156 parents of children without ADHD. In
      addition to examining both traditional and parenting-specific alcohol
      expectancies for these adults, risk variables cutting across the two groups were
      considered: single parenthood and male gender. Few differences in mean expectancy
      levels were found between parents of children with and without ADHD, between
      single and married mothers, and between men and women. Furthermore, expectancies
      did not predict drinking differently across groups. However, there was some
      support for the utility of assessing parental expectations of alcohol's effects
      on interactions with children, and there were robust and interesting effects of
      socioeconomic status on expectancies and drinking. Single mothers also reported
      consuming higher quantities of alcohol than married mothers. Findings are
      discussed in terms of the link between ADHD and alcoholism, the ability of
      alcohol expectancies to explain drinking differences between high risk groups,
      the effect of socioeconomic status on these variables, and single motherhood as a
      vulnerability factor for increased drinking.

PMID- 9161618
TI  - Voices of the afflicted.
AB  - Over the past 10 years, I have been privileged to conduct educational forums for
      audiences containing many recovering alcoholics or otherwise chemically dependent
      persons. In these forums about the addictive diseases and their treatment and
      research possibilities, significant interaction with the audience members occurs.
      During these interactions, certain anecdotal phenomena seem to predominate. The
      repetitive nature of these reports suggests the need for systematic
      investigation. As with editorial comments in major medical journals, observed
      phenomena and unanswered questions from those afflicted can be valuable in the
      generation of testable hypotheses. Perhaps the ideas presented herein will be
      useful in the development of future research on alcohol abuse and alcohol
      dependence.

PMID- 9161619
TI  - Consensus panel advocates prolonged interferon treatment for chronic hepatitis C.

PMID- 9161620
TI  - New bisphosphonate approved for Paget's disease.

PMID- 9161621
TI  - Failure to implement U.S. needle-exchange program has cost many lives and
      dollars, study says.

PMID- 9161622
TI  - Liability for expanded responsibilities.

PMID- 9161623
TI  - Predicting look-alike and sound-alike medication errors.
AB  - A model for predicting medication name confusion is described. Many medication
      errors are caused by look-alike and sound-alike medication names, yet few
      procedures exist to ensure the safety of new drug nomenclature or to identify
      confusingly similar names from within existing databases. In this study, three
      automated, quantitative measures of orthographic similarity (i.e., similarity in
      spelling) were identified (bigram similarity, trigram similarity, and Levenshtein
      distance). The relationship between orthographic similarity and the likelihood of
      a medication error was examined. For each measure of similarity, the frequency
      distribution of similarity scores for pairs of drug names previously reported to
      cause confusion (error pairs) was compared with the distribution of similarity
      scores for control pairs randomly selected from the general index of USP DI
      Volume I: Drug Information for the Health Care Professional. Then, three
      parallel, unmatched case-control studies were conducted to discover whether
      similarity was a significant risk factor for medication errors. Finally, on the
      basis of the three similarity measures, tests for predicting confusion were
      developed and evaluated. For each similarity measure, the frequency distribution
      of error pairs was significantly different from that for control pairs, and
      orthographic similarity was a significant risk factor for medication errors.
      Pairs of names whose measures of similarity exceeded present thresholds were
      between 25 and 523 times more likely to be involved in a medication error than
      pairs whose similarity did not exceed these thresholds. A prognostic test that
      correctly identified 91% of all pairs as either errors or controls was developed.
      This test had a sensitivity of 84% and a specificity of 99%. Automated measures
      of similarities between medication names can form the basis of highly accurate,
      sensitive, and specific tests of the potential for errors with look-alike and
      sound-alike medication names.

PMID- 9161624
TI  - Cardiovascular effects of i.v. granisetron at two administration rates and of
      ondansetron in healthy adults.
AB  - The cardiovascular effects of granisetron given as a 30-second i.v. bolus dose
      and of granisetron and ondansetron given by currently recommended methods were
      studied. Healthy adults 18 to 50 years of age were randomly assigned to one of
      four treatments during each of four study periods: granisetron 10 micrograms/kg
      (as the hydrochloride salt) i.v. over 5 minutes, granisetron 10 micrograms/kg
      i.v. over 30 seconds, ondansetron 32 mg (as the hydrochloride salt) i.v. over 15
      minutes, and placebo. During each study period, the researchers gave each subject
      three sequential injections using a double-blind, double-dummy technique. Each
      subject was to receive all four regimens. Two resting 12-lead electrocardiograms
      (ECGs) were obtained before the regimen, and one was obtained at the end of each
      injection and at intervals up to 24 hours after the third injection. Sitting
      blood pressure and pulse were measured before treatments, immediately after the
      end of each injection, and at intervals up to 24 hours after injection 3. Safety
      data were analyzed for 13 subjects, and ECG interval data for 12 of them. The
      mean postdose QTc interval differed significantly among regimens. There were no
      other significant regimen-associated differences among the four mean results for
      any ECG interval. The mean post-dose QTc interval for ondansetron was
      significantly greater than that for each of the other regimens. The drug regimens
      were comparable in safety and tolerability. A total of 20 adverse effects, all
      mild to moderate, were reported in 10 subjects. Changes in vital signs were
      minimal. There were no clinically important cardiovascular changes associated
      with the i.v. administration of granisetron 10 micrograms/kg over 30 seconds,
      granisetron 10 micrograms/kg over 5 minutes, or ondansetron 32 mg over 15 minutes
      in healthy adults.

PMID- 9161625
TI  - Adverse drug reactions in home care patients receiving nafcillin or oxacillin.
AB  - Documented adverse reactions to anti-infective agents in patients of a home
      infusion company were studied to determine whether the prevalence of reactions
      was greater in patients receiving nafcillin or oxacillin than in those receiving
      other i.v. antiinfectives. Data on adverse drug reactions (ADRs) were obtained by
      reviewing the discharge summaries of all patients who received anti-infective
      therapy in 1990-1994 and the company's quarterly and annual ADR reports for that
      period. The occurrence of ADRs per total courses of therapy was calculated for
      groups of antiinfectives, as were intensity and causality. For ADRs to nafcillin
      and oxacillin, patient demographics and treatment information and outcomes were
      reviewed. A total of 2488 courses of anti-infective therapy were documented, and
      ADRs occurred in 10.9%. Nafcillin and oxacillin accounted for 105 courses, with
      an ADR rate of 31.4%; 99 patients received one of these drugs and 24 had ADRs,
      with rash and phlebitis the most common ADRs. Thirty-nine patients receiving
      nafcillin or oxacillin had documented infection with methicillin-sensitive
      Staphylococcus aureus. Seventy-five patients receiving nafcillin or oxacillin did
      not have an ADR; therapy was successful in 62 of these patients. Of the 24
      patients with ADRs to nafcillin or oxacillin, 13 were switched to other i.v. anti
      infectives, which were successful in 10 of them. Five patients were hospitalized
      because of ADRs to nafcillin or oxacillin. Most nafcillin or oxacillin ADRs that
      resulted in a therapy change or hospitalization occurred in the second or third
      week of therapy. Home care patients who received nafcillin or oxacillin therapy
      had a disproportionately high number of ADRs, compared with patients who received
      other anti-infective agents.

PMID- 9161626
TI  - Economic evaluation of famciclovir in reducing the duration of postherpetic
      neuralgia.
AB  - The economic impact of famciclovir therapy for postherpetic neuralgia (PHN) in
      patients with acute herpes zoster was studied. A decision-analytic model of the
      treatment of herpes zoster and PHN was used to compare the cost of PHN between
      patients treated with oral famciclovir 500 mg three times daily for seven days
      and patients not receiving any antiviral therapy. The effects of famciclovir on
      PHN in the model were based on the results of a randomized, double-blind trial in
      419 adult outpatients. The cost of the course of famciclovir therapy (21 tablets)
      was estimated as the sum of the drug's wholesale acquisition cost and the
      pharmacy dispensing cost. The cost of treating PHN (physician visits,
      medications, and miscellaneous nondrug therapy) was estimated by consulting a
      panel of physicians. According to the model, the cost of treating PHN was $85
      lower per famciclovir recipient ($294 for famciclovir versus $379 for no
      antiviral therapy). The net cost of famciclovir therapy was $23 per patient ($108
      for acquisition and dispensing minus the $85 savings). Among patients 50 years of
      age or older, famciclovir reduced the average cost of PHN by $155 ($414 for
      famciclovir versus $569 for no antiviral therapy) and yielded a net savings of $7
      per patient. A model for the use of famciclovir to treat acute herpes zoster
      showed that the cost of such therapy was largely offset by savings in the cost of
      treating this complication.

PMID- 9161627
TI  - Pharmacoeconomic model of enoxaparin versus heparin for prevention of deep vein
      thrombosis after total hip replacement.
AB  - The costs of heparin and enoxaparin to prevent deep vein thrombosis (DVT) after
      total hip replacement in the U.S. treatment environment were compared. A decision
      model was used in a pharmacoeconomic comparison of subcutaneous enoxaparin and
      subcutaneous heparin, each given for seven days, for the prophylaxis of DVT. In
      the model, three outcome pathways could follow prophylaxis: proximal DVT, distal
      DVT, and no DVT (but with a possible false-positive clinical diagnosis of DVT).
      Probabilities of thromboembolic events and major bleeding were derived from three
      randomized clinical trials. Account was also taken of the effects of pulmonary
      embolism (PE). Pharmacoeconomic studies and expert opinion were relied on for the
      model's principal resource-use categories and costs for DVT prophylaxis, clinical
      diagnosis of DVT and PE, and DVT and PE treatment. The outcome of choice for the
      model was the number of DVT events avoided. Regardless of the trial data used,
      the total mean cost of enoxaparin prophylaxis ($3336 to $3380) exceeded the cost
      of heparin prophylaxis ($3292 to $3330). However, enoxaparin was more cost
      effective in avoiding DVT than heparin, irrespective of the trial on which the
      analysis was modeled. A sensitivity analysis involving length of hospital stay
      and length of prophylactic therapy showed the model to be robust and gave the
      advantage in all instances to enoxaparin in cost per DVT avoided. A model of
      enoxaparin versus heparin DVT prophylaxis after total hip replacement showed that
      enoxaparin was more costly than heparin in overall expected treatment costs but
      more cost-effective in the avoidance of DVT.

PMID- 9161628
TI  - Supportive care during aldesleukin therapy for patients infected with human
      immunodeficiency virus.

PMID- 9161629
TI  - Compatibility of ciprofloxacin lactate with sodium bicarbonate during simulated Y
      site administration.

PMID- 9161630
TI  - Multidisciplinary approach to reducing costs in a health system.

PMID- 9161631
TI  - Nonprescription drugs in Hungary.

PMID- 9161632
TI  - Advice on treatment of Mycobacterium avium complex infection.

PMID- 9161633
TI  - Controversies in diagnosis and management of recurrent spontaneous abortion.

PMID- 9161634
TI  - Monoclonal antibodies as direct probes for human sperm acrosome reaction.
AB  - PROBLEM: To develop simple and rapid assay procedures for determining human sperm
      acrosome reaction under various experimental conditions. METHODS: Specific
      monoclonal antibodies against human sperm acrosome were generated and utilized as
      probes for acrosome reaction assays by direct labelling of antibodies with
      fluorescein-isothiocyanate (FITC). RESULTS: Among the generated monoclonal
      antibodies, HS-63 was shown to react with antigens in the acrosome content of
      permeabilized acrosome-intact human sperm, but not with those of the live ones.
      HSA-10 was found to recognize antigens on the surface of sperm inner acrosome and
      to react with acrosome-reacted human sperm in suspension. Following a swim-up
      procedure, highly motile sperm were recovered and incubated in BWW medium at 37
      degrees C for 18 h. The percentages of acrosome-reacted sperm were determined at
      various incubation times by using FITC-labeled HS-63 or HSA-10 as the indicators
      in 10 min direct immunofluorescent assay. With the FITC-labeled HS-63 probe, the
      percentage of positively stained human sperm fixed in methanol decreased
      significantly after 18 h of incubation from > 90 to 70-80%. In contrast,
      positively stained live human sperm by HSA-10 increased significantly from < 1%
      to 15-30%. A high correlation was obtained between the use of monoclonal
      antibodies and PSA (Pissum sativum agglutinin) for direct assessment of human
      sperm acrosome reaction. CONCLUSION: In view of the simplicity in assay
      procedures and evaluations, these FITC-labeled monoclonal antibodies are reliable
      probes for direct assessment of acrosomal status of human sperm.

PMID- 9161635
TI  - Acrobeads test as a predictor of fertilization in vitro.
AB  - PROBLEM: To determine whether the results of the Acrobeads test, which measures
      the expression of the complement regulator molecule CD46 on the inner acrosomal
      membrane following the acrosome reaction, accurately identifies semen specimens
      that will exhibit reduced or failed fertilization following conventional IVF
      insemination. METHOD: The Acrobeads test was performed on semen specimens from 97
      consecutive patients preparing to undergo an IVF cycle utilizing a standardized
      insemination protocol. Motile sperm populations were examined at 6 h and 24 h
      post-isolation for sperm-bead agglutination. Results of the Acrobeads test were
      compared to that of TRITC-PSA staining in matched specimens to directly measure
      the spontaneous loss of acrosome content. The percentages of TRITC-PSA-negative
      sperm were determined in freshly isolated motile populations and in duplicate
      aliquots incubated 18 to 20 h under sperm capacitating conditions. The
      relationship between the results of both analyses estimating spontaneous acrosome
      reactions and the rate of fertilization of metaphase II oocytes was examined.
      RESULTS: The Acrobeads score did not correlate significantly with the rate of
      fertilization by insemination at 6 h or at 24 h. The negative predictive value of
      this test was 21.4%. There was no correlation between the Acrobeads score and the
      percentage of sperm undergoing a spontaneous acrosome reaction as detected by
      TRITC-PSA labeling. In contrast, the increment increase in the percentage of
      spontaneous acrosome reactions as quantified by TRITC-PSA staining was correlated
      with the fertilization rate. CONCLUSIONS: Contrary to previous reports, our
      prospective, double-blinded study failed to demonstrate that the Acrobeads test
      can accurately predict fertilization outcome in IVF. Therefore, the routine use
      of this test to screen patients prior to an IVF cycle in order to select
      appropriate treatment (i.e., ICSI) cannot be recommended.

PMID- 9161636
TI  - Comparison of the immunobead binding test (IBT) and immunospheres (IS) assay for
      detecting serum antisperm antibodies.
AB  - PROBLEM: The IBT is considered the gold standard of sperm antibody assays. This
      test uses polyacrylamide beads labeled with antiglobulins (anti-IgG, anti-IgA,
      and anti-IgM), which bind to the corresponding antibody on the sperm surface. The
      IS uses color-coded latex beads of uniform 3.0 microns size coated with the
      antiglobulins which can be viewed with brightfield light microscopy. The purpose
      of the present study was to compare the IBT and IS in an indirect test using
      human serum. METHOD: Serum specimens (n = 42) were tested for the presence of
      antibody isotypes IgG, IgA, and IgM to sperm using the standard protocol for IBT
      and IS. Donor sperm was washed in BWW with 5% BSA and diluted to a final
      concentration of 50 x 10(6) motile sperm/ ml. The sperm were incubated with a
      1:10 dilution of test serum for 30 min to 1 h at 37 degrees C and then washed by
      three cycles of centrifugation. The sperm and beads (IBT, IS) were mixed on a
      glass slide, covered with a coverslip, and observed within 5 min. At least 100
      motile sperm were counted and scored for bead binding. A specimen was considered
      positive if 20% or more of the sperm were coated with one or more beads. The data
      were analyzed using calculation of the non-parametric kappa statistic with
      correction for chance expected agreement, and by calculating the proportion of
      specific agreement between the two methods. RESULTS: The results are summarized
      in the following table: [table see text]; The IS was able to detect 94% of IgG
      antibodies, 91% of IgA antibodies, and 100% of IgM antibodies. One serum specimen
      was IgG negative by IS (14% binding), but positive by IBT (20%). A second serum
      specimen was IgA negative by IS (16%) yet positive by IBT (29%). There were no
      false positives with the IS assay. Of the IgM positives (five of six) occurred
      alone and not with IgG or IgA, suggesting the necessity for testing all specimens
      also for IgM. CONCLUSION: Antisperm antibody test results obtained by the IS
      assay are in agreement with the results obtained with the IBT test. The
      Immunospheres are monodispersed, color coded, and can be visualized with
      brightfield microscopy.

PMID- 9161637
TI  - Distinct expression of cytokines and mitogenic inhibitory factors in semen of
      fertile and infertile men.
AB  - PROBLEM: To assess the effect of seminal plasma (SP) of fertile and infertile men
      on leukocyte mitogenic response, and the capability of sperm cells to produce IL
      1. METHODS: This study included four groups: fertile men (donors, normal),
      infertile men with azoospermia (azoo), oligo-terato-asthenozoospermia (OTA), and
      OTA with genital infection (OTA-inf). Mouse spleen cell proliferation in response
      to lipopolysaccharide (LPS) or Concanavalin-A (Con-A) was examined in the
      presence of SP from the above four groups. Supernatants (sup) and lysates (lys)
      of sperm cells from fertile and oligoteratoasthenospermic (OTA) men were
      evaluated for IL-1 bioactivity by specific bioassay. RESULTS: Seminal plasma (SP)
      of the four groups were shown to inhibit the mitogenic response of mouse spleen
      cells to LPS and Con-A. SP of fertile men was significantly more inhibitory than
      SP from infertile men. Sperm cells from fertile and OTA infertile men
      constitutively produced IL-1. Sperm cells of both groups produced similar levels
      of IL-1 as examined in the supernatants and lysates. CONCLUSIONS: Seminal plasma
      of fertile men had more inhibitory mitogenic activity than that of OTA. Sperm
      cells constitutively produce IL-1. It is possible that the factors involved in
      this inhibition are not only anti-proliferative immune factors. Cytokines and
      inhibitory factors of mitogenesis in the seminal plasma may be involved in the
      physiology and pathophysiology of sperm functions and thus affect male fertility.

PMID- 9161638
TI  - Efficacy of intracytoplasmic sperm injection (ICSI) treatment in the
      immunological infertile patients.
AB  - PROBLEM: To evaluate the efficacy of intracytoplasmic sperm injection (ICSI)
      treatment in the immunological infertile patients. METHODS: The subjects were 60
      cycles of 44 immunological infertile patients and these clinical data were
      analysed, retrospectively. They were classified into female and male
      immunological infertility group and were treated with conventional IVF, ICSI, and
      half-ICSI. RESULTS: The fertilization rate of ICSI (60.3%) and half-ICSI (60.7%)
      cycles were significantly (P < 0.01) higher than conventional IVF (42.6%) cycles.
      In the male immunological infertility group, fertilization rate was significantly
      (P < 0.01) higher in ICSI (60.7%) and half-ICSI (66.7%) cycles than in
      conventional IVF (27.4%) cycles and clinical pregnancy rate was higher in ICSI
      (54.5%) and half ICSI (33.3%) than in conventional IVF (25.0%) cycles.
      CONCLUSIONS: We suggest that ICSI treatment is highly effective method to improve
      fertilization and pregnancy rate in IVF-ET program of male immunological
      infertility.

PMID- 9161639
TI  - Correlation of basal menses CA-125 levels and 6 month pregnancy rates in women
      undergoing treatments for infertility without assisted reproductive methods.
AB  - PROBLEM: The objective of this study was to evaluate the correlation of menstrual
      CA-125 levels with pregnancy rates (PRs) after 6 months of treatment for
      infertility. METHOD: The sample consisted of a heterogenous group of 160 women
      who sought treatment for infertility. Treatments include progesterone
      supplementation, donor insemination, intrauterine insemination, and ovulation
      induction therapy. No laparoscopies were done during the study period. A baseline
      CA-125 level was drawn during menses before the initiation of therapy. Patients
      were followed for 6 months of treatment or until a pregnancy was achieved.
      RESULTS: There was no difference in the 6 month PR or viable PR by CA-125 level.
      CONCLUSIONS: Elevated CA-125 levels are not predictive of poor fertility
      potential at least during the first 6 months of infertility therapy. Even though
      these higher levels sometimes suggest that endometriosis is present, the data
      suggest that correction of male factor, cervical factor or ovulation factor
      provides effective PRs without the need for laparoscopic intervention.

PMID- 9161640
TI  - Human endometrial leukemia inhibitor factor (LIF) secretion and its relationship
      to sonographic endometrial appearance.
AB  - PROBLEM: LIF is believed to be involved in human reproduction. Because little is
      known about the function of this cytokine in proliferative phase of cycle and
      because LIF is found to regulate the cellular growth we evaluated the possible
      relationship between endometrial LIF secretion and endometrial growth. METHOD:
      The present is prospective, blinded study with clinical and immunobiochemical
      correlation between endometrial LIF concentration and endometrial ultrasound
      pattern. Twenty-four patients who were candidates for IVF and oocyte donation are
      included in this study. At day 10 of their cycle the endometrial biopsy was
      performed, followed by vaginal sonographic measurements of endometrial thickness
      and pattern. Endometrial LIF concentration was measured by ELISA in supernatants
      taken from cultured explants. RESULTS: Endometrial LIF production significantly
      negatively correlated with endometrial thicknesses (P < 0.05). There was a 4-fold
      elevation in LIF production when the endometrial thickness was below 5 mm. Strong
      correlation was found also between endometrial LIF production and sonographic
      endometrial pattern (P < 0.05). The most significant amount of LIF was found in
      nonfavorable endometria. CONCLUSION: In the proliferative phase of cycle there is
      a dynamic relationship between endometrial sonographic appearance and local LIF
      secretion. Specifically LIF production is negatively correlated with endometrial
      thickness and pattern. The low amount of cytokine is a normal uteral environment
      for endometrial development, whereas deregulation of cytokine production toward
      its overexpression may lead to a strong inhibitory effect on endometrial growth.
      This finding might have an important clinical implication.

PMID- 9161641
TI  - Differential expression of IGF-I and IGF-II in eutopic and ectopic endometria of
      women with endometriosis and in women without endometriosis.
AB  - PROBLEM: Factors regulating the development, growth, and differentiation of
      endometrial cells of endometriotic lesions are poorly understood. To investigate
      the paracrine-autocrine regulation of ectopic endometrial cell growth, the
      expression of IGF-I and IGF-II were studied. METHOD: Tissue specimens of eutopic
      and ectopic endometria were obtained from eight patients with endometriosis at
      laparoscopy and from the endometria of 14 women without endometriosis as
      controls. They were tested for the expression of IGF-I and IGF-II by
      immunohistochemical analysis. RESULTS: Immunohistochemical study for IGF-I in
      controls showed a more intense staining during the proliferative phase both in
      stromal and epithelial cells. In eutopic endometria of women with endometriosis a
      reduction in the staining was observed, whereas in epithelial cells of fibrotic
      peritoneal adhesions an intense immunostaining for IGF-I was observed.
      Immunohistochemical study of IGF-II in controls showed a more intense staining
      during secretory phase both in stromal and epithelial cells. In eutopic
      endometria of women with endometriosis, a reduction in the staining was observed,
      whereas in epithelial cells of fibrotic peritoneal adhesions an intense
      immunostaining for IGF-I was observed. Immunohistochemical study of IGF-II in
      controls showed a more intense staining during secretory phase both in stromal
      and epithelial cells. In eutopic endometria of women with endometriosis, a
      reduction in the staining was observed, whereas in epithelial cells of ovarian
      lesions and fibrotic peritoneal adhesions, no immunostaining for IGF-II was
      observed. CONCLUSIONS: In endometriosis there is an alteration of mechanisms
      regulating cell proliferation and differentiation.

PMID- 9161642
TI  - Expression of an immunomodulatory protein known as progesterone induced blocking
      factor (PIBF) does not correlate with first trimester spontaneous abortions in
      progesterone supplemented women.
AB  - PROBLEM: An immunomodulatory protein known as the progesterone induced blocking
      factor (PIBF) has been found to positively correlate with early pregnancy beta
      human chorionic gonadotropin (B-hCG) levels. The study presented herein evaluated
      PIBF levels from conception to the end of the first trimester to determine if
      lower levels will correlate with first trimester spontaneous abortions (SAB).
      METHOD: Progesterone induced blocking factor expression by lymphocytes measured
      using an immunocytochemistry method was compared in pregnant women with ongoing
      vs. failed pregnancies. RESULTS: There were no differences in the proportion of
      women having lymphocytes expressing PIBF or in the median numbers when comparing
      ongoing vs. failed pregnancies. There was no B-hCG interval where failed
      pregnancies were found to have lower frequency of PIBF expressing lymphocytes.
      CONCLUSION: Inadequate PIBF expression independent of low P levels does not
      appear to be an etiologic factor for first trimester SABs; thus measuring this
      protein in pregnant women lacks practical usefulness.

PMID- 9161643
TI  - Inappropriate prescribing and health outcomes in elderly veteran outpatients.
AB  - OBJECTIVE: To determine the relationship of inappropriate prescribing in the
      elderly to health outcomes. SETTING: General Medical Clinic of the Durham
      Veterans Affairs Medical Center. PATIENTS: A total of 208 veterans more than 65
      years old who were each taking five or more drugs and participated in a
      pharmacist intervention trial. MEASUREMENTS: Prescribing appropriateness was
      assessed by a clinical pharmacist using the medication appropriateness index
      (MAI). A summed MAI score was calculated, with higher scores indicating less
      appropriate prescribing. The health outcomes were hospitalization, unscheduled
      ambulatory or emergency care visits, and blood pressure control. RESULTS:
      Bivariate analyses revealed that mean MAI scores at baseline were higher for
      those with hospital admissions (18.9 vs. 16.9, p = 0.07) and unscheduled
      ambulatory or emergency care visits (18.8 vs. 16.3, p = 0.05) over the subsequent
      12 months than for those without admissions and emergency care visits. MAI scores
      for antihypertensive medications were higher for patients with inadequate blood
      pressure control (> 160/90 mm Hg) than for those whose blood pressure was
      controlled (4.7 vs. 3.1, p = 0.02). CONCLUSIONS: Inappropriate prescribing
      appeared to be associated with adverse health outcomes. This findings needs to be
      confirmed in future studies that have larger samples and control for potential
      confounders.

PMID- 9161644
TI  - Reliability of drug utilization evaluation as an assessment of medication
      appropriateness.
AB  - OBJECTIVE: To test the reliability of drug utilization evaluation (DUE) applied
      to medications commonly used by the ambulatory elderly. METHODS: A DUE model was
      developed for four domains: (1) justification for use, (2) critical process
      indicators, (3) complications, and (4) clinical outcomes. DUE criteria specific
      to use in the elderly were developed for angiotensin-converting enzyme (ACE)
      inhibitors and histamine2 (H2)-antagonists, and consensus was reached by an
      external expert panel. After pilot testing, two clinical pharmacists
      independently evaluated these medications, applying the DUE criteria and rating
      each item as appropriate or inappropriate. Interrater and intrarater reliability
      was assessed by using kappa statistics. RESULTS: In a sample of 208 ambulatory
      elderly veterans, 42 (20.2%) were taking an ACE inhibitor and 56 (26.9%) an H2
      antagonist. The interrater agreement for individual domains, represented by kappa
      statistics, were 0.10-0.58 and 0-0.83 for ACE inhibitors and H2-antagonists,
      respectively. The kappa statistic for overall agreement, which considered ratings
      from all criteria across all domains, was 0.24 for ACE inhibitors and 0.18 for H2
      antagonists. Intrarater reliability was assessed 3 months later, and kappa
      statistics were 0.61-0.65 (0.49 overall) and 0-0.96 (0.81 overall) for ACE
      inhibitors and H2-antagonists, respectively. CONCLUSIONS: Intrarater reliability
      for DUE was good to excellent. However, interrater reliability exhibited only
      marginal reproducibility, particularly where evaluators were required to use
      subjective judgement (i.e., complications, clinical outcomes). DUE may not be a
      suitable standard for assessing medication appropriateness in ambulatory elderly
      patients.

PMID- 9161645
TI  - Reliability of a modified medication appropriateness index in ambulatory older
      persons.
AB  - OBJECTIVE: To evaluate the reliability of a medication appropriateness index
      (MAI) modified for elderly outpatients in a non-Veterans Affairs setting. DESIGN:
      Reliability study. SETTING: General community. PARTICIPANTS: Ten community
      dwelling elderly (> 65 y) taking five or more regularly scheduled medications and
      participating in a university-based health service intervention study. MAIN
      OUTCOME MEASURES: Interrater reliability of MAI ratings of 65 medications made by
      two clinical pharmacists for individual items and for an overall summed score was
      calculated by use of kappa statistics and intraclass correlation coefficient.
      RESULTS: The interrater agreement for each of the individual MAI items was high
      for both appropriate and inappropriate ratings and ranged from 80% to 100%
      (overall kappa = 0.64). Overall agreement for the summed score was good
      (intraclass correlation = 0.80). CONCLUSIONS: The modified MAI is a reliable
      instrument for evaluation of medication appropriateness in a non-Veterans
      Affairs, ambulatory, elderly population and may provide pharmacists with a
      practical and standard method to evaluate patients' drug regimens and identify
      some potential drug-related problems.

PMID- 9161646
TI  - Comparative study of bioavailability and clinical efficacy of carbamazepine in
      epileptic patients.
AB  - OBJECTIVE: To compare the bioavailability of three generic brands of
      carbamazepine tablets with that of a proprietary brand in adult patients with
      epilepsy. DESIGN: A double-blind, randomized, three-phase crossover study.
      SETTING: A psychiatric facility. PARTICIPANTS: Eighteen patients with epilepsy
      who had taken carbamazepine at least 5 months before entering the study. MAIN
      OUTCOME MEASURES: Ten blood specimens from each patient were collected at steady
      state. Plasma concentration of carbamazepine was analyzed for pharmacokinetic
      parameters such as maximum plasma concentration (Cmax), mean time to reach
      maximum concentration (tmax), and mean AUC. RESULTS: There were no statistically
      significant differences in these parameters among four brands of carbamazepine.
      However, when comparing the 90% CI of AUC of three generic brands with that of
      the proprietary brand, the AUC of two generic brands lay within a range of 80% to
      120%. The effects of gender and each brand of carbamazepine on these
      pharmacokinetic parameters were also analyzed. Breakthrough seizures occurred
      even though the plasma concentration of carbamazepine was therapeutic.
      CONCLUSIONS: The bioavailability of two generic brands of carbamazepine tablets
      (Carmapine and Carzepine) and the proprietary brand (Tegretol) were equivalent in
      this sample of adult patients with epilepsy.

PMID- 9161647
TI  - Stability of fosphenytoin sodium with intravenous solutions in glass bottles,
      polyvinyl chloride bags, and polypropylene syringes.
AB  - OBJECTIVE: To determine the stability of fosphenytoin sodium admixtures with NaCl
      0.9% injection and dextrose 5% (D5W) injection when stored in glass or polyvinyl
      chloride (PVC) containers, to evaluate the compatibility of fosphenytoin with 11
      other intravenous solutions, and to determine the stability of fosphenytoin
      repackaged in polypropylene syringes. METHODS: Dilutions of fosphenytoin sodium
      1, 8, and 20 mg phenytoin sodium equivalents (PE)/mL were prepared in NaCl 0.9%,
      D5W, and 11 other intravenous fluids. Aliquots of each solution in NaCL 0.9% or
      D5W were transferred to three glass bottles for storage at 25 degrees C and 21
      PVC bags for storage at 25, 4, or -20 degrees C. Aliquots of each admixture with
      the other intravenous fluids were transferred to three PVC bags and stored at 25
      degrees C for 7 days. In addition, 63 syringes were filled with fosphenytoin
      sodium 50 mg PE/mL (undiluted) and stored at 25, 4, or -20 degrees C. Samples of
      each solution from the three containers were analyzed for visual compatibility,
      pH, and fosphenytoin concentration initially and at 0.5, 1, 2, 3, 7, 14, and 30
      days during storage at 25 and 4 degrees C and at 1, 7, 14, and 30 days during
      storage at -20 degrees C. Following removal of containers from the freezer,
      additional samples were obtained after 7 days at 4 or 25 degrees C, and 7 days at
      25 degrees C, and then 7 days at -20 degrees C. RESULTS: No visible precipitation
      or change in color or clarity was observed in any of the fosphenytoin solutions
      during the study. The concentration of fosphenytoin at each sampling time
      remained within 97-104% of initial concentration, regardless of container,
      concentration, intravenous admixture, or storage temperature. CONCLUSIONS:
      Fosphenytoin sodium, either undiluted in polypropylene syringes or diluted with
      NaCl 0.9% or D5W in PVC bags, remains stable for at least 30 days at room
      temperature, under refrigeration, or frozen. After removal from the freezer,
      fosphenytoin can be thawed, kept at 4 or 25 degrees C for 7 days, and then
      returned to the freezer for another 7 days. Admixtures of fosphenytoin sodium in
      various other intravenous fluids are stable for at least 7 days at room
      temperature.

PMID- 9161648
TI  - Topical antimicrobial prophylaxis in minor wounds.
AB  - OBJECTIVE: To evaluate the ability of a novel topical antimicrobial gel
      containing cetrimide, bacitracin, and polymyxin B sulfate to prevent infections
      of minor wounds. DESIGN: A clinical trial compared the test preparation with
      placebo and a povidone iodine antiseptic cream. SETTING: Five primary schools in
      Sydney, Australia, participated in the study over a 6-week spring/summer school
      term. SUBJECTS: Children aged 5-12 years with parental consent were eligible for
      study participation. Accidental injuries occurring at school were treated in a
      standardized manner by nurses at each site. OUTCOME MEASURES: Wounds were
      evaluated by the medical practitioner after 3 days of topical treatment. The
      clinical outcome was classified as resolution or suspected infection. If a
      clinical infection was suspected, the injury was swabbed for microbiologic
      evaluation. Growth of a dominant microorganism was classified as a microbiologic
      infection. RESULTS: Of the 177 injuries treated, there were nine clinical
      infections. A comparison of these showed a significant difference among treatment
      groups (p < 0.05). This difference was associated with the test preparation and
      placebo; the test preparation reduced the incidence of clinical infection from
      12.5% to 1.6% (p < 0.05; 95% CI, 0.011 to 0.207). A comparison of microbiologic
      infections showed no significant differences among treatment groups (p > 0.05).
      CONCLUSIONS: The novel gel preparation containing cetrimide, bacitracin, and
      polymyxin B sulfate showed therapeutic action and reduced the incidence of
      clinical infections in minor accidental wounds. It may be a suitable product for
      first aid prophylaxis.

PMID- 9161649
TI  - Development of an intravenous-to-oral route conversion program for antimicrobial
      therapy at a Canadian tertiary care health facility.
AB  - OBJECTIVE: To describe the effect of introducing a route conversion program on
      the prescribing of antimicrobials for the treatment of respiratory tract
      infections and skin/soft tissue infections in a sample population. DESIGN:
      Concurrent, pre- and postintervention study. SETTING: Four general internal
      medicine wards at The Toronto Hospital, a 1170-bed, tertiary care health center
      in Toronto, Ontario, Canada. PARTICIPANTS: Patients receiving antimicrobial
      therapy for respiratory tract infections and skin/soft tissue infections.
      INTERVENTION: Written guidelines and education sessions were presented to
      residents, interns, medical students, and pharmacists responsible for the care of
      patients admitted to four general internal medicine wards. MAIN OUTCOME MEASURES:
      Clinical and laboratory parameters related to the status of the infection were
      monitored prospectively and compared with the course of drug therapy, with
      consideration of the patient's ability to meet the criteria established in the
      guidelines. The number of days of intravenous therapy prescribed despite
      appropriateness of oral therapy was tallied. RESULTS: Twenty-seven patients (28
      infections) were identified for inclusion in the 7-week preliminary audit, and 30
      patients (32 infections) were included in the audit after the program, which
      continued for 5 weeks. Following implementation of the program, the number of
      days that intravenous therapy was continued despite the appropriateness of oral
      therapy was reduced from 41% to 26% of the total days of intravenous therapy
      prescribed. CONCLUSIONS: The program had a positive influence on antimicrobial
      prescribing behavior in the population studied. Strategies to ensure continued
      benefit from the program have been developed.

PMID- 9161650
TI  - Nifedipine interaction with tacrolimus in liver transplant recipients.
AB  - OBJECTIVE: To examine the possible drug interaction between nifedipine and
      tacrolimus in liver transplant recipients. STUDY DESIGN: A retrospective study
      was done comparing two groups of liver transplant recipients. The starting time
      for comparison was the same after transplant. One group (n = 22) consisted of
      hypertensive patients who were treated with nifedipine; the other group (n = 28)
      did not receive nifedipine. The two groups were compared over 1 year. The effect
      of nifedipine on tacrolimus was measured in terms of tacrolimus whole blood
      trough concentrations, daily tacrolimus dosages, and cumulative tacrolimus
      dosages at 1, 3, 6, and 12 months. All patient charts were reviewed with regard
      to concurrent medication that could affect the metabolism of tacrolimus and
      eventually affect tacrolimus concentrations and dosages. DATA COLLECTION: All
      required information was retrieved from medical records. RESULTS: There was a
      statistically significant difference between daily dosage requirements of
      tacrolimus at 90 (p = 0.03), 180 (p = 0.004), and 365 (p = 0.0004) days between
      the nifedipine and no-nifedipine groups. The tacrolimus daily dosage in the
      nifedipine group was decreased by 26%, 29%, and 38% at 3, 6, and 12 months,
      respectively, compared with the dosage of the no-nifedipine group. Statistically
      significant differences in cumulative dosages of tacrolimus were observed at 180
      (p = 0.02) and 365 (p = 0.003) days between the nifedipine and no-nifedipine
      groups, with cumulative dosage reduction of 25% and 31% by 6 and 12 months,
      respectively, in the nifedipine group compared with the no-nifedipine group.
      CONCLUSIONS: Nifedipine decreased the daily and cumulative dosage requirement of
      tacrolimus. The interaction observed between nifedipine and tacrolimus is the
      first reported in humans and is clinically important. As a result of this drug
      interaction, it is recommended that blood concentrations of tacrolimus be
      monitored during coadministration of these drugs and that the tacrolimus dosage
      be adjusted accordingly.

PMID- 9161651
TI  - Interaction between quinupristin/dalfopristin and cyclosporine.
AB  - OBJECTIVE: To describe a case of a drug interaction between cyclosporine and
      quinupristin/dalfopristin (QND). CASE SUMMARY: A patient who had undergone a
      kidney transplant and was receiving chronic cyclosporine therapy was treated with
      the investigational streptogramin antibiotic QND. Baseline trough cyclosporine
      concentrations ranged from 80 to 105 ng/ml. Two and 3 days after initiation of
      QND therapy, trough cyclosporine concentrations increased to 261 and 291 ng/mL,
      respectively. Following discontinuation of QND, the cyclosporine blood
      concentration decreased and the dosage was subsequently increased to the previous
      regimen. DISCUSSION: A patient's cyclosporine blood concentration tripled 3 days
      after initiating therapy with QND. A one-third reduction in the cyclosporine
      dosage was required. QND was the most likely cause for the change in cyclosporine
      blood concentrations, probably due to inhibition of cyclosporine metabolism. This
      represents the first published case of an interaction between cyclosporine and
      QND. CONCLUSIONS: Frequent monitoring of cyclosporine concentrations with
      attention to the need for dosage modification is recommended when initiating or
      discontinuing QND therapy.

PMID- 9161652
TI  - Fluvoxamine for stereotypic behavior in patients with dementia.
AB  - OBJECTIVE: To describe the effects of treatment with the selective serotonin
      reuptake inhibitor fluvoxamine on three patients with advanced dementia who
      developed a stereotypic movement disorder. CASE SUMMARY: Three patients in a
      skilled nursing facility were referred by their primary physicians for
      psychiatric consultation to assist with the management of stereotypic behaviors.
      The patients received a standard medical, neurologic, and psychiatric workup for
      dementia. Two of the patients were diagnosed with dementia of the Alzheimer type
      and the other patient was diagnosed with vascular dementia. All three patients
      were started on fluvoxamine 25 mg/d; behaviors were monitored daily by the
      nursing staff and their primary care physicians and weekly by their psychiatrist
      using the Abnormal Involuntary Movement Scales. The dosage was titrated upward
      weekly to a maximum dosage of 150 mg/d. RESULTS: Two patients showed complete
      resolution of their stereotypic behaviors by week 6. The third patient showed
      noticeable improvement with some residual movements after 8 weeks of treatment.
      CONCLUSIONS: Fluvoxamine appeared effective in the control of stereotypic
      behaviors in three patients with advanced dementia.

PMID- 9161653
TI  - Spironolactone-induced agranulocytosis.
AB  - OBJECTIVE: To report a case of agranulocytosis secondary to spironolactone in a
      patient with cryptogenic liver disease. CASE SUMMARY: A 58-year-old Hispanic
      woman with cryptogenic cirrhosis was admitted to University Hospital on October
      31, 1995. Laboratory data revealed a leukocyte count of 1.0 x 10(3)/mm3 and an
      absolute neutrophil count (ANC) of 10 cells/mm3. Prior to treatment with
      spironolactone, the leukocyte count was 10.2 x 10(3)/mm3 and ANC 8400 cells/mm3.
      Agranulocytosis resolved 5 days following the discontinuation of spironolactone.
      Results from the bone marrow biopsies before and after treatment with
      spironolactone suggested that agranulocytosis was caused by the drug's toxic
      effect on the bone marrow. DISCUSSION: Drug-induced agranulocytosis is a serious
      adverse effect, occurring at a rate of approximately 6.2 cases per million
      persons each year. In addition to the case reported here, three other reports of
      agranulocytosis secondary to spironolactone have been published in the
      literature. Several factors have been identified that may increase a patient's
      risk for developing agranulocytosis, including increased age, hepatic or renal
      impairment, drug dosage and duration, and concurrent medications. CONCLUSIONS:
      Agranulocytosis secondary to spironolactone is a serious potential adverse
      effect. Patients with risk factors for developing this adverse effect should be
      closely monitored since early detection and discontinuation of spironolactone can
      improve prognosis.

PMID- 9161654
TI  - Generalized seizures associated with the use of muromonab-CD3 in two patients
      after kidney transplantation.
AB  - OBJECTIVE: To report two cases of seizures associated with the use of muromonab
      CD3. CASE SUMMARY: Two uremic cadaveric kidney transplant recipients had
      developed generalized seizures following administration of muromonab-CD3 within
      the first 2 days after transplantation. Seizures were treated successfully with
      intravenous phenytoin, and muromonab-CD3 administration was discontinued.
      DISCUSSION: The overall frequency of seizures during muromonab-CD3 administration
      is 6%. Uremia in patients in the early posttransplant period appears to
      predispose them to seizures. Seizures that happened to our two uremic patients
      after transplant suggest that they had been induced by muromonab-CD3
      administration. The mechanism of how this could have induced seizures is unknown.
      CONCLUSIONS: Prophylactic muromonab-CD3 should be used carefully in uremic kidney
      transplant recipients following surgery. If therapy with muromonab-CD3 is
      necessary early hemodialysis should be considered in an effort to lower the risk
      of seizures.

PMID- 9161655
TI  - Nitroprusside treatment of erythromelalgia in an adolescent female.
AB  - OBJECTIVE: To report a case of erythromelalgia in an adolescent patient
      successfully treated with nitroprusside. CASE SUMMARY: A 15-year-old girl with
      erythromelalgia resistant to aspirin therapy received an infusion of
      nitroprusside. The response of the erythromelalgia to nitroprusside was dramatic,
      with complete pain resolution within 17 hours after the start of therapy. No
      relapse of erythromelalgia was seen when nitroprusside was discontinued and the
      patient remained well after 6 months. DISCUSSION: This case adds to existing
      literature substantiating the benefit of nitroprusside for the treatment of
      erythromelalgia in pediatric patients. Erythromelalgia in children may represent
      a different disease entity than that seen in adults, which is commonly responsive
      to aspirin therapy. The pathogenesis of erythromelalgia is unclear and precludes
      formulating a proposed mechanism by which nitroprusside has benefit in children.
      CONCLUSIONS: Nitroprusside is valuable for erythromelalgia resistant to aspirin
      therapy in pediatric patients. Because of unanswered questions regarding the
      disease, aspirin remains the agent of first choice in all patients with this rare
      disease.

PMID- 9161656
TI  - Acute asthma associated with sustained-release verapamil.
AB  - OBJECTIVE: To describe a patient with asymptomatic bronchial asthma and
      hypertension who developed an acute asthma attack after receiving sustained
      release verapamil. CASE SUMMARY: A 66-year-old white woman with a 10-year history
      of hypertension and bronchial asthma was switched from immediate-release
      verapamil hydrocloride 40 mg tid to sustained-release verapamil 240 mg/d po for
      better hypertension control. After taking the first tablet, she developed
      dyspnea, cough, and wheezing. Antiasthmatic medications were prescribed, but the
      asthma symptoms did not improve. She continued taking verapamil for 6 months,
      then, on her own, stopped all medications including the sustained-release
      verapamil, and her asthma symptoms disappeared. On rechallenge she developed
      severe dyspnea, cough, and wheezing 20 minutes after administration. The asthma
      resolved within 24 hours following three albuterol inhalations. The next day
      similar symptoms developed with rechallenge of the same brand of sustained
      release verapamil in a 120-mg formulation, and verapamil was discontinued. Six
      months later she was again prescribed sustained-release verapamil 240 mg in
      another clinic where the physician was unaware of her previous reaction. Once
      again, severe dyspnea, cough, and wheezing developed. DISCUSSION: On four
      separate occasions the patient was challenged advertently or inadvertently, with
      sustained-release verapamil. Similar symptoms developed after each challenge and
      resolved after discontinuing this preparation. Although dyspnea associated with
      verapamil administration has been reported, this is the first report of an
      elderly asymptomatic asthmatic patient with hypertension who developed an acute
      asthma attack following sustained-release verapamil administration. CONCLUSIONS:
      Sustained-release verapamil is thought to be the cause of the asthma attack in
      this patient because she was not taking any other preparations; the symptoms
      started with the administration of sustained-release verapamil and were relieved
      after its discontinuation.

PMID- 9161657
TI  - Cost-effectiveness of thrombolytic therapy for acute myocardial infarction.
AB  - OBJECTIVE: To estimate the cost-effectiveness of thrombolytic therapy versus no
      thrombolytic therapy for patients following acute myocardial infarction, focusing
      on the impact of time to treatment on outcome. METHODS: A decision model was
      developed to assess the benefits, risks, and costs associated with thrombolytic
      therapy for treatment of acute myocardial infarction compared with standard
      nonthrombolytic therapy. The model used pooled data from a recent study of nine
      large randomized, controlled clinical trials and 12-month outcome data from a
      recently published meta-analysis of thrombolytic therapy trial data. Outcomes
      were expressed in terms of survival to hospital discharge and survival to 1 year
      after discharge. The risks of treatment that led to death, morbidity, or added
      costs were estimated. The model determined excess and marginal costs per death
      averted to hospital discharge and at 1 year. Results were also estimated in terms
      of cost per year of life saved. Sensitivity analyses included variations in time
      to treatment and drug cost. RESULTS: The marginal cost of thrombolytic therapy
      per death averted at 1 year was $222,344, or $14,438 per year of life saved. For
      patients treated within 6 hours of acute myocardial infarction, the marginal cost
      per death averted was $181,536 at 1 year, or $11,788 per year of life saved.
      CONCLUSIONS: Thrombolytic therapy is significantly more cost-effective than many
      other cardiovascular interventions and compares favorably with other forms of
      medical therapy. Results suggest that shortening the time to treatment has a
      critical impact on the cost-effectiveness of thrombolytic therapy.

PMID- 9161658
TI  - Consensus guidelines for coordinated outpatient oral anticoagulation therapy
      management. Anticoagulation Guidelines Task Force.
AB  - OBJECTIVE: To provide primary and referring healthcare practitioners with
      guidelines for the provision of safe and effective anticoagulation management in
      any venue to standardize and improve quality of care and to permit negotiation
      for reimbursement from third-party payers. DATA EXTRACTION AND SYNTHESIS: Data on
      the current practice of anticoagulation providers and outcomes related to
      anticoagulation clinic care were obtained through the literature, interviews with
      anticoagulation providers, and a focus group meeting of anticoagulation clinic
      stakeholders. This information collation process revealed that an anticoagulation
      service consists of three separate areas for which guidelines should be
      developed. Based on the consensus opinions of the committee members, the
      literature review, and the current practice of anticoagulation services
      providers, a draft guideline was developed and reviewed by an independent
      multidisciplinary panel of anticoagulation services providers whose comments were
      incorporated into the final guideline. CONCLUSIONS: Systematic outpatient
      anticoagulation services are systems of care designed to coordinate and optimize
      the delivery of anticoagulation therapy by (1) evaluating patient-specific risks
      and benefits to determine the appropriateness of therapy; (2) facilitating the
      management of anticoagulation dosages and prescription pick up or delivery; (3)
      providing ongoing education of the patient and other caregivers about warfarin
      and the importance of self-care behavior leading to optimal outcomes; (4)
      providing continuous systematic monitoring of patients, international normalized
      ratio results, diet, concomitant drug therapy, and disease states; and (5)
      communicating with other healthcare practitioners involved in the care of the
      patient. To create a reproducible framework for the provision of these services,
      guidelines for structure, process, and outcomes of coordinated outpatient
      anticoagulation management services were developed. Guidelines for organization
      and management include (1) qualifications for personnel, (2) supervision, (3)
      care management and coordination, (4) communication and documentation, and (5)
      laboratory monitoring. Guidelines for the process of patient care include (6)
      patient selection and assessment, (7) initiation of therapy, (8) maintenance and
      management of therapy, (9) patient education, and (10) management and triage of
      therapy-related and unrelated problems. Guidelines for the evaluation of patient
      outcomes include (11) organizational components and (12) patient outcomes. The
      impact of these 12 guidelines on patient care and reimbursement procurement will
      depend on their implementation and the perceived value of their use.

PMID- 9161659
TI  - Pegaspargase: an alternative?
AB  - OBJECTIVE: To review the chemistry, pharmacology, pharmacokinetics, clinical
      activity, adverse effects, dosage, and administration guidelines for
      pegaspargase. DATA SOURCES: A MEDLINE search (1980-1996), a CANCERLIT search
      (1983-1996), and a CURRENT CONTENTS search (1980-1996) using the terms
      pegaspargase, PEG-asparaginase, PEG-L-asparaginase, polyethylene glycol L
      asparaginase, polyethylene glycol conjugated L-asparaginase, and Oncaspar were
      conducted. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for
      possible inclusion in this review. Abstracts were included only when they were
      judged to add critical information not otherwise available in the medical
      literature. DATA SYNTHESIS: L-Asparaginase has been a main component of treatment
      regimens for acute lymphocytic leukemia. A key limiting factor of L-asparaginase
      use has been the development of hypersensitivity to the drug. Recently, a
      polyethylene glycol (PEG) conjugated form of L-asparaginase, pegaspargase, has
      been made available. PEG modification of L-asparaginase has been shown to alter
      the tendency of the enzyme to induce an immune response and to extend the half
      life of the drug. The majority of patients with hypersensitivity to the native
      enzyme preparations tolerate pegaspargase without further clinical
      hypersensitivity. The adverse effect profile of pegaspargase is similar to that
      of the native forms of L-asparaginase. The recommended dosage of pegaspargase is
      2500 IU/m2 administered by intramuscular or intravenous injection every 2 weeks
      in combination with other chemotherapeutic agents. CONCLUSIONS: Pegaspargase is a
      safe, effective alternative to L-asparaginase in patients who have had clinical
      hypersensitivity reactions to both Escherichia coli- and Erwinia carotovora
      derived L-asparaginase. However, pegaspargase should not be routinely substituted
      for L-asparaginase.

PMID- 9161660
TI  - Zolpidem: distinct from triazolam?
AB  - OBJECTIVE: To review the literature that compares zolpidem with triazolam, with
      an emphasis on efficacy and safety in humans. DATA SOURCES: Information was
      retrieved from a MEDLINE search (1983-1996) of the English-language literature
      using the terms triazolam and zolpidem. STUDY SELECTION: Reports of clinical
      trials comparing the safety and efficacy of zolpidem and triazolam were included
      in this review. DATA EXTRACTION: Data were evaluated according to study design,
      efficacy, and adverse effects. Pertinent information was selected and the data
      synthesized into a review format. DATA SYNTHESIS: Zolpidem and triazolam have
      similar pharmacokinetic and pharmacodynamic effects in humans. Clinical trials
      have shown that usually recommended, equipotent dosages of zolpidem and triazolam
      do not differ with respect to pharmacokinetics, efficacy, tolerability, residual
      effects, memory impairment, rebound insomnia, abuse potential, or other adverse
      effects. CONCLUSIONS: Zolpidem offers no distinct therapeutic advantage over
      triazolam for the treatment of insomnia.

PMID- 9161661
TI  - Doxepin in the management of pruritus associated with allergic cutaneous
      reactions.
AB  - The primary treatment of urticaria involves identification and discontinuation of
      the offending agent. Addition of an antihistaminic agent may then be necessary to
      control pruritus. Because of variable response rates between patients, several
      alternative agents may need to be tried before the most effective regimen is
      found. Based on the studies reviewed here, it appears that low-dose doxepin (10
      mg po tid) is a potentially effective and well-tolerated alternative in patients
      who do not respond to conventional antihistamines. This success may be in part
      due to the more potent H1- and H2-blocking properties associated with doxepin.
      Data regarding the topical use of doxepin are less convincing; however, the drug
      appears to have some clinical use for the short-term treatment of pruritus.
      Doxepin cream does not appear to be as effective as systemic therapy, and adverse
      effects (including sedation) and drug interactions are still problematic. Topical
      use may be best suited to conditions involving intact skin that do not require
      application to large areas of the body, thereby reducing systemic absorption and
      adverse effects.

PMID- 9161662
TI  - Effect of intermittent hemodialysis on nondepolarizing skeletal muscle relaxants.

PMID- 9161663
TI  - Fludrocortisone in the treatment of subarachnoid hemorrhage-induced hyponatremia.
AB  - Hyponatremia, natriuresis, and a decrease in plasma volume of greater than 10%
      occurs in approximately 50% of the patients with aneurysmal SAH, perhaps due to
      SIADH and CSWS. However, fluid restriction, as indicated in SIADH, might result
      in vasospasm and cerebral infarction in these patients. Maintaining intravascular
      volume seems to be important in SAH; several reports suggest that cerebral
      ischemia can be reversed by use of volume expanders. Fludrocortisone has been
      shown to reduce natriuresis, which may help maintain plasma volume in patients
      with SAH. Adequate oral salt intake also appears to have possible therapeutic
      benefit in these patients. However, it remains unproven whether fludrocortisone
      results in a decreased incidence of cerebral ischemia. Larger controlled trials
      are needed to ascertain the impact of fludrocortisone on prevention of cerebral
      ischemia in patients with SAH.

PMID- 9161664
TI  - The role of dehydroepiandrosterone in AIDS.
AB  - The use of DHEA for the treatment of AIDS shows some promise, although controlled
      trials have not been performed to evaluate its efficacy. Low serum concentrations
      of DHEA have been correlated with states of decreased immune function in humans,
      since concentrations are lowest in early childhood, late adulthood, and as HIV
      disease progresses. DHEA appears to possess immunomodulating effects, perhaps by
      enhancing the secretion of IL-2 from activated T cells as demonstrated in a
      murine model. A decline in DHEA concentrations, particularly when initially less
      than 2.01 micrograms/L, might also prove to be a predictor of HIV disease
      progression. It is also plausible that a decrease in DHEA concentrations can be
      used to predict a decline in overall health status. Although the role of DHEA in
      the treatment of AIDS has not yet been determined, the drug appears to show
      potential for clinical benefit that should be evaluated in large, randomized,
      controlled trials.

PMID- 9161665
TI  - Medication appropriateness index: putting a number on an old problem in older
      patients.

PMID- 9161666
TI  - Pharmacoeconomic analysis of administration of famotidine i.v. push
      vs.intermittent slow i.v. infusion.

PMID- 9161667
TI  - Erythropoietin to treat anemia of prematurity.

PMID- 9161668
TI  - Potential interaction between tramadol and warfarin.

PMID- 9161669
TI  - Hypoprothrombinemia during concomitant therapy with warfarin and saquinavir.

PMID- 9161670
TI  - Comment: possible toxicity from propylene glycol in lorazepam infusion.

PMID- 9161671
TI  - Correction: RSV immune globulin intravenous.

PMID- 9161672
TI  - Health promotion: an essential component of rehabilitation for persons with
      chronic disabling conditions.
AB  - This qualitative study was undertaken to clarify an emerging explanatory model of
      health-promoting behaviors, and quality of life in individuals with chronic
      disabling conditions. Twenty individuals with multiple sclerosis shared their
      stories regarding health promotion, domains of quality of life, and factors that
      affected these domains. Health-promoting behaviors were viewed as essential to
      the process of rehabilitation and maintaining an acceptable quality of life.
      Important quality-of-life issues were related to domains other than function.
      Implications are that health promotion efforts need to be encouraged and
      supported in individuals with chronic disabling conditions.

PMID- 9161673
TI  - Responding to threats to integrity of self.
AB  - Current theories of illness focus either on the illness experience or on the
      response to recovery from particular diseases. When the focus is on the
      individual, rather than the cause, it is evident that these experiences may be
      combined to develop a comprehensive theory that incorporates the individual's
      responses to acute or chronic illness or to injury. Extending primarily from the
      illness Constellation Model and Preserving Self, a five-stage model, Responding
      to Threats to Integrity of the Self, was developed. The theory focuses on the
      individual (and to a lesser degree on the individual's family) and how the
      individual seeks self-comforting strategies to mediate the experience. The theory
      is one of recovery and rehabilitation, is comprehensive, and may be used for
      understanding and supporting patient responses.

PMID- 9161674
TI  - Beyond "true" and "false" memories: remembering and recovery in the survival of
      childhood sexual abuse.
AB  - As survivors of childhood sexual abuse (CSA) struggle to grasp and reclaim their
      selves, their stories, and their futures from the grip of aftereffects of trauma,
      the processes of recovery and rehabilitation are interwoven with remembering.
      Questions about women's delayed memories of CSA have stirred a controversy that
      places clients' credibility at stake. Nurses need to understand the historical
      and political roots of this controversy and to be familiar with the empirical
      knowledgebase that exists about traumatic memory. This article is a critical
      feminist analysis of the topic. Its purposes are to provide a historical context
      for the current debate about "true" and "false" CSA memories; to discuss selected
      literature about conventional understandings of memory and their relevance to
      this debate; to present an integrative, phenomenological approach to memory in
      the recovery and rehabilitation of women CSA survivors; and to use the insights
      gained to draw conclusions from a nursing perspective about the authenticity of
      delayed CSA memories. Phenomenological concepts of reminding, reminiscing,
      recognition, body memory, place memory, and commemoration are discussed as they
      illuminate the complexity of traumatic memories and the recovery and
      rehabilitation needs of survivors of childhood sexual abuse.

PMID- 9161675
TI  - The role of nursing in the rehabilitation of acute stroke patients: toward a
      unified theoretical perspective.
AB  - A review of existing literature indicates an uncertainty about the specific
      therapeutic role of nurses in the rehabilitation of stroke patients. Two
      different conceptualizations of the nursing role exist, but neither is related to
      specific rehabilitation goals and patient outcomes. A beginning theoretical
      account of the specific role of nursing in stroke recovery is offered as a
      structure to integrate the therapeutic aspects of the coordinating, maintenance,
      and training functions of the nurse. Existing research literature is reviewed to
      substantiate the account. Further research is needed to develop the specific
      content and focus of nursing in stroke recovery.

PMID- 9161676
TI  - Breast cancer survival: a phenomenological inquiry.
AB  - This inquiry describes the experience of 45 female breast cancer survivors using
      Schutz's interpretation of phenomenology as the theoretical framework. The
      research design is a multicase, comparative situational analysis. Breast cancer
      survival is explored from the points of view of all study participants. A
      dialectic is formed that juxtaposes etic and emic views of survival to enhance
      understanding of the meaning of breast cancer survival. Hermeneutic analysis
      yielded commonalities in meanings, situations, and life experiences. Analysis was
      further divided into thematic analysis, depiction of exemplars, and paradigm
      cases to provide clarity and vividness to the multifaceted phenomenon of breast
      cancer survival.

PMID- 9161677
TI  - Psychological well-being of Cambodian women in resettlement.
AB  - Current literature focuses on immediate needs of refugees as they flee acute
      crises. However, the search for refuge extends beyond immediate migration.
      Refugees confront many issues in resettlement. The experience of traumatic pain
      and multiple losses coupled with the struggle for survival in a foreign community
      places them at risk for diminished health and psychological well-being. The
      notion of recovery extends to the period of resettlement. It is imperative that
      nursing professionals examine assumptive biases that hinder the care and recovery
      of refugees. This article seeks to heighten professional awareness about issues
      that confront Cambodian women in resettlement by examining these biases.

PMID- 9161678
TI  - Cranial non-metric variation in north and central Mexico.
AB  - Fifty cranial non-metric traits were scored on twenty series of crania from north
      and central Mexico in the American Museum of Natural History. Additional crania
      from three of the series were scored in the Musco Nacional de Antropologia.
      Mexico City. Although a total of 471 crania and 316 mandibles were registered,
      only 11 series containing 387 crania and 270 mandibles, were of sufficient length
      for statistical analysis. Trait frequencies in these series were compared by
      multidimensional scaling and principal component analysis. The results suggest a
      degree of biological continuity in the Basin of Mexico over a twenty-five hundred
      year period, although the later samples from that area exhibit signs of some gene
      flow from more northern populations.

PMID- 9161679
TI  - A discriminant analysis approach to morphological regionalization in the European
      Late Mesolithic.
AB  - The morphological regionalization of European Mesolithic populations was studied
      by discriminant analysis. Samples from four localities were compared employing
      craniometric variables. The general conclusion was that there is evidence for
      regionalization in the Late mesolithic in Europe, and a clinical pattern of
      variation was not detected. These results are in agreement with archaeological
      reconstructions of the population structure in the Late Mesolithic Europe.

PMID- 9161680
TI  - Identification of protostylid.
AB  - The presence of the protostylid was determined on 942 extracted lower molars of
      recent Slovenians. Dental casts of 32 extracted molars exhibiting a protostylid
      pit were obtained from alginate as well as from silicone impressions. The quality
      of the reproduction of protostylid pits was determined and the identification of
      these on dental casts was compared with their identification on the extracted
      teeth. The presence of the protostylid pit was confirmed histologically. Compared
      with previous studies the results show a higher frequency of protostylid on the
      third molars (51.2%); 70.3% of these protostylids relate to surface
      irregularities and are as such much readily observable by the protostylid pit.
      Determination of protostylid pits from the casts made from silicone impressions
      is more reliable compared to the same determination from the casts obtained from
      alginate impressions. The former method may be even more reliable than
      determination on the extracted teeth. Owing to common local enamel hypoplasias on
      the third molars, there is a considerable possibility of misjudging the presence
      of a protostylid if the determination is not confirmed histologically. Though the
      identification of the protostylid is difficult because of its poor expressivity,
      the accuracy of investigations would significantly increase if protostylids on
      lower third molars were given more attention. By doing so the data on frequency
      and expressivity of this dental trait would be of more value.

PMID- 9161681
TI  - Polymorphism of conventional genetic markers and HLA system in Turkey.
AB  - This study is part of a general survey in which the regional variability of
      various genetic markers in Turkey will be analyzed with special regard to its
      application in forensic medicine. Blood samples from 3173 unrelated healthy
      individuals of both sexes and from different regions of Turkey have been sampled
      and were typed for the blood group polymorphisms AB0, MNSs, Kell, Duffy, Kidd, P,
      Lutheran and Lewis, for the red cell enzyme polymorphisms adenylate kinase (AK),
      glyoxalase (GLO), phosphoglucomutase (PGM), esterase D (ESD), red cell acid
      phosphatase (aP), and for the serum protein polymorphisms group specific
      component (vitamin D binding protein, GC) and transferrin (TF). In addition to
      this the HLA-A and HLA-B antigens of the major histocompatibility complex (HLA)
      were also typed in 973 individuals. The blood group polymorphisms were typed by
      the classical haemagglutination methods. Serum protein and red cell enzyme
      polymorphisms were determined by conventional cellulose acetate electrophoresis.
      HLA antigens were typed by the standard two stage microlymphocytotoxicity
      technique. Genetic equilibrium can be assumed for all polymorphic systems under
      study. The results indicate some regional differences in the distribution of
      allele frequencies.

PMID- 9161682
TI  - A comparison of interalar width and intercanine distance in Malay males and
      females.
AB  - The interalar width of the nose and the intercanine distance were measured in 266
      Malay subjects (111 males and 155 females) randomly selected from the students of
      the School of Medical Sciences. University Sains Malaysia in Kota Bharu,
      Malaysia. The mean interalar width of the nose in male subjects was 39.8 +/- 2.3
      mm (range 34-45 mm) and in female subjects 36.2 mm +/- 2.2 mm (range 30-41 mm).
      There is a statistically significant difference (t = 12.9: p < 0.05) in the nasal
      width between male and female Malay subjects. This agrees with the findings of
      other similar studies that males have wider noses than females. The mean
      maxillary intercanine distance in male subjects was 36.7 = 2.6 mm (range 30-42
      mm) and in female subjects 36.2 = 2.3 mm (range 30-42 mm). The anterior maxillary
      arch is significantly wider in Malay subjects compared to Chinese from Singapore
      (Keng 1986) as p < 0.05 and to Caucasians (Sawiris 1977) as p < 0.05. There is a
      significant correlation (r = 0.312; p < 0.05) between the nasal width and the
      intercanine distance in female subjects but not in male subjects.

PMID- 9161683
TI  - Genetic and environmental factors affecting menarcheal age in Spanish women.
AB  - Genetic and environmental contributions to menarcheal age were studied in 267
      Spanish girls and women born between 1948 and 1981, and their mothers born
      between 1922 and 1959 (n = 200). Recalled age at menarche, as well as family
      environment characteristics (family size, birth order, father's occupation and
      father's educational level) were obtained from each woman. Mean age at menarche
      in mothers (13.45 years; SD = 1.51) was significantly (p < 0.01) greater than in
      daughters (13.03 +/- 1.28 years). Year of birth and family size accounted for a
      significant amount of the variation in age at menarche in both mothers and
      daughters, whereas occupation of the father only appeared related to menarcheal
      age in the mothers subsample. Birth order and father's educational level did not
      contribute significantly to the age at menarche. The mother-daughter and sister
      sister correlations (maximum likelihood estimates) for age at menarche were 0.30
      and 0.35, respectively (both significant at p < 0.001). This supports the genetic
      and environmental contribution to the age at menarche, even though the influence
      of environmental variables may change over time.

PMID- 9161684
TI  - An examination of the relationship between foot length, foot breath, ball girth,
      height and weight of Turkish university students aged between 17 and 25.
AB  - In this study the relationship between foot length, foot breadth, ball girth or
      foot circumference, height and weight of Turkish students aged between 17 and 25
      was examined. It was noted that in both sexes the correlation between foot length
      and height was more significant than the correlation between foot length and
      weight. When the percentage ratio of foot breadth and ball girth to foot length
      is calculated in both sexes, the percentage ratio in students with longer feet
      turned out to be smaller. However, it was found that foot breadth and ball girth
      of the male students in the same foot length category were greater than in the
      female students. The comparison of right foot length and ball girth in the same
      foot length category in Turkish, French and Japanese indicated that there was a
      similarity between Turkish and French with regard to foot breadth. The ball girth
      of the individuals from these three different populations were quite different
      from each other. It was observed that the average foot length of the Turkish was
      larger than that of both French and Japanese. The following conclusions can be
      drawn from this study: 1. Foot breath, ball girth and foot length can be regarded
      as three separate elements. 2. These three elements are to be precisely known for
      the optimal manufacturing of shoe lasts. 3. Apart from the above mentioned three
      elements, both individual and racial differences must also be considered
      concerning an optimal manufacturing of shoe lasts.

PMID- 9161685
TI  - Precise analyses of the structure of the thymus for establishing details of the
      mechanisms underlying thymocyte proliferation and maturation.
AB  - Details of thymocyte proliferation and maturation are important for understanding
      the variability of T cell functions. The following aspects need to be clarified
      in this context: 1) Ascertaining why hematopoietic committed pre-T cells
      migrating in the blood stream are trapped and proliferate in the subcapsular
      region of the thymus. Further morphological and functional studies of stromal
      cells in situ in the thymus should be conducted. The factors responsible for
      thymocyte proliferation should be also analysed. 2) How phenotypic maturation of
      thymocytes takes place and how T-cell receptor (TCR) expression is processed and
      controlled. 3) Subsequently, how does the selection of thymocytes take place? Is
      negative selection in fact responsible for the unresponsiveness of the body to
      self antigens? Further morphological analyses of thymic epithelial cells,
      thymocytes themselves and macrophages need to be conducted, together with
      immunohistochemical analyses using many monoclonal antibodies directed against
      these cells and the extracellular matrix, in order to analyse the cellular
      dynamics and cell-to-cell interactions occurring in thymus tissues in situ. 4)
      How mature thymocytes migrate to the periphery: Perivascular structures and the
      cells accumulating in this space should be intensively analysed morphologically
      and phenotypically. Lymphatic structures related to the thymus tissues also
      remain to be studied. To understand these questions, several useful experimental
      systems can also be employed: 1) Phylogenetical analyses, 2) ontogenical
      analyses, 3) thymus tissues regenerating from radiation or thymotoxic drugs, 4)
      thymomas, and 5) thymus tissues from transgenic animals. These important problems
      could be further studied in such experimental models both morphologically and
      immunohistochemically, since many useful tools are now available for studies of
      phenotypic and other markers of thymocytes and thymic epithelial cells.
      Subsequently, further detailed analyses of thymic structures may shed more light
      on the mechanisms underlying thymocyte proliferation and maturation.

PMID- 9161686
TI  - Characterization of the human thymic microenvironment: lymphoepithelial
      interaction in normal thymus and thymoma.
AB  - Recent advances in tissue culture technology and molecular biology have extended
      our understanding of the functional morphology of the thymus. The importance of a
      crosstalk between lymphoid cells and stroma has been appreciated as a
      prerequisite for the normal development of both. The network of direct cellular
      interactions and soluble factors comprising part of the microenvironment is far
      from being elucidated but the highly ordered thymic architecture clearly plays a
      pivotal role in normal thymic function. Insight into the genetic control of
      stroma development is only emerging while knowledge on the genetic control of the
      various steps in T cell development is already advanced and rapidly expanding.
      The present paper gives an overview on the cellular components and matrix
      molecules of the human thymic microenvironment and their development during
      ontogeny. The intrathymic cytokine network is shortly reviewed. Special emphasis
      is put on molecules mediating lymphoepithelial interactions that are necessary
      for the expansion and early selection of immature thymocytes from precursor cells
      and for the generation of an MHC restricted and self tolerant T cell repertoire
      by positive and negative selection. Considering these physiological mechanisms we
      summarize the molecular pathology of the microenvironment and lymphocyte/stroma
      interactions in thymic epithelial tumors (thymomas). Finally, a pathogenetic
      model for paraneoplastic myasthenia gravis is given. We suggest abnormal auto
      antigen-specific positive selection of naive T cells as the essential molecular
      mechanism by which thymomas contribute to the autoimmunization against the
      acetylcholine receptor and other muscle proteins.

PMID- 9161687
TI  - Sex hormones and the thymus in relation to thymocyte proliferation and
      maturation.
AB  - This paper reviews the mechanism of sex hormone actions on the thymus, presenting
      mainly our data obtained at the cellular and molecular levels. First, data
      supporting the "genomic" action via the nuclear sex hormone receptor complexes
      are as follows: 1) sex hormone receptors and the thymic factor (thymulin) are co
      localized in thymic epithelial cells, but not in T cells; 2)
      production/expression of thymic factors (thymulin, thymosin alpha 1) are
      remarkably inhibited by sex hormone treatment; 3) sex hormones cause changes in T
      cell subpopulations in the thymus; and 4) sex hormones strongly influence the
      development of thymus tumors in spontaneous thymoma BUF/Mna rats through their
      receptor within the tumor cells. Secondly, data indicating the "non-genomic"
      action of sex hormones via a membrane signal-generating mechanism are as follows:
      1) the proliferation/maturation of thymic epithelial cells is mediated through
      protein kinase C activity introduced by sex hormones; 2) sex hormones directly
      influence DNA synthesis and cdc2 kinase (cell cycle-promoting factor) activity.

PMID- 9161688
TI  - Thymic nurse cells forming a dynamic microenvironment in spontaneous thymoma
      BUF/Mna rats.
AB  - Thymic nurse cells (TNCs) were studied using an animal model, BUF/Mna rats, which
      spontaneously develop benign thymomas of epithelial origin with age. The unusual
      increment and high availability of TNCs in this thymus enabled us to analyze TNCs
      directly either in tissue sections or on smears after enzymatic isolation. No
      structural or phenotypical abnormality in these TNCs was detected as assessed by
      electron microscopy and immunohistochemistry. Typical TNCs were widely
      distributed in the cortical areas but not in the medullary areas. They showed
      characteristic euchromatic bright nuclei and enclosed intra-TNC cells with an
      investment of relatively light cytoplasm with abundant small vesicles and rough
      endoplasmic reticulum. The intra-TNC cells were mostly double positive (CD4+CD8+)
      cortical thymocytes, though macrophage populations could also be distinguished by
      their content of membrane-bounded phagosomes, multivesicular bodies and other
      inclusion bodies, and by their lack of cytoskeletal keratin filaments. High
      voltage electron microscopy revealed that intra-TNC cells were separated into
      several compartments by extremely thin internal veils of the TNC processes. The
      outer veils of the TNCs were continuous with occasional small gaps through which
      intra-TNC cells could migrate in and out of the compartments. Immunohistochemical
      analyses revealed that the TNCs per se were positive for MHC class I and class
      II, keratin and thymulin, but lacked both lymphocyte and macrophage markers.
      Among all adhesion molecules tested, ICAM-1 was strongly expressed on almost all
      TNCs. A minority of TNCs also contained either LFA-1 alpha or LFA-1 beta positive
      cells. These results suggest that TNCs may form a rather dynamic microenvironment
      for T cell development where either nursing or clearance of thymocytes take
      place, depending on the cellular components of intra-TNC cells. Macrophage
      populations may also play crucial roles as the third component within TNCs.

PMID- 9161689
TI  - Heterogeneity of mouse thymic macrophages: I. Immunohistochemical analysis.
AB  - As the first step toward understanding the identity and functions of thymic
      macrophages in situ, we examined the phenotypic heterogeneity of mouse thymic
      macrophages in tissue sections by the immunohistochemical double staining method
      with four monoclonal antibodies (F4/80, Mac-2, anti-CD32/16 and anti-I-A
      antibodies) as macrophage markers. Morphologically, three types of macrophages
      were identified: dendritic, round and flat-shaped. Dendritic macrophages were
      scattered throughout the thymus, and most of them were stained by all four
      markers. Among these macrophages, those at the cortico-medullary region (CMR)
      expressed a high intensity of CD32/16 antigen. Round macrophages were also
      distributed throughout the thymus; most of them, however, were localized in the
      cortico-medullary region to the medulla. These cells were F4/80-negative, Mac-2
      positive, CD32/16-negative and I-A-positive. In contrast, round macrophages
      located at the cortex expressed F4/80. Flat-shaped macrophages were localized at
      the subcapsular region of the cortex where active lymphopoiesis was observed.
      This type was positive for F4/80 and CD32/16, but negative for Mac-2.
      Furthermore, most of the three types of thymic macrophages showed intense
      reactions of the I-A antigen within the cytoplasm in addition to the expression
      of I-A antigen on the cell membrane. These results indicate that morphological
      characteristics of thymic macrophages at different locations reflect phenotypic
      variations detected in immunohistochemistry, and suggest that these different
      type macrophages may play distinct roles at various locations in thymocyte
      development in the thymus.

PMID- 9161690
TI  - Glucocorticoid-induced thymocyte death in the murine thymus: the effect at later
      stages.
AB  - SUMMARY: Although glucocorticoid has been considered to cause thymocyte apoptosis
      in vitro, few studies have presented its in vivo effect. We report here on
      kinetics of glucocorticoid-induced murine thymocyte death in vivo by the TUNEL
      method. TUNEL-positive cells were observed as early as at 2 h after
      intraperitoneal injection of glucocorticoid. Most TUNEL-positive thymocytes were
      phagocytosed by acid phosphatase positive macrophages. "Free" (not phagocytosed)
      TUNEL-positive cells were not detected at early stages (by 4 h). At 6 to 8 h
      after the injection, the number of phagocytosed thymocytes per individual
      macrophage had reached its maximum, and at 8 to 12 h many ruptured macrophages
      ingesting too many dying thymocytes became noticeable. During the process, no
      additional macrophages appeared to be mobilized to the thymus. At 6 to 8 h after
      the injection, however, coincidentally with the fact that macrophages had become
      unable to further ingest dying lymphocytes, dead cells were left unphagocytosed,
      and ultimately became "free" positive cells, probably due to some proteolytic
      process ongoing within the thymus. As late as at 12 h, morphological examination
      revealed that epithelial cells seemed to begin engulfing thymocytes, almost
      simultaneously with the start of rupture of the macrophages due to the ingestion
      of too many thymocytes. Epithelial cells were readily identified by desmosomes
      and tonofilaments, in addition to euchromatic nuclei. Altogether, these results
      suggest that: 1) even though thymocytes were exposed to glucocorticoid in vivo,
      most of them were not TUNEL-positive unless they were phagocytosed; 2) even after
      most macrophages had ingested too many cells at later stages, macrophages in
      other locations did not migrate to the thymus; and finally, 3) deletion of
      damaged thymocytes was also carried out by thymic epithelial cells, though not
      frequently, at around 12 h and later.

PMID- 9161691
TI  - Morphological and flow cytofluorometrical analyses of regenerated rat thymus
      after irradiation.
AB  - Reconstituted rat thymuses were studied by immunohistochemistry, transmission
      electron microscopy (TEM) and flow cytofluorometry on days 0, 1, 2, 3, 5, and 7
      after whole-body sublethal irradiation (6 Gy). One day after irradiation,
      numerous apoptotic cells were seen in the cortical thymus; the percentage of the
      sub-G1 peak representing apoptotic cells was 8.9% in the DNA content histogram of
      cytofluorometry. On day 3, the thymic structure had been destroyed and no
      distinction was drawn between the cortex and medulla. In this stage, few
      thymocytes but many macrophages were present, and the percentage of the sub-G1
      peak reached a peak at 13.0%. Bromodeoxyuridine (BrdU) incorporated cells
      gradually increased after irradiation, and immunohistochemically numerous
      apoptotic cells were found primarily in the cortex on day 7. These thymocytes
      showed some levels of electron density of the nucleus as revealed by TEM. The
      percentage of S phase cells did not change markedly (20-30%) based on one-color
      DNA content histograms, but the percentage of early S and S phase cells was
      extremely high on day 7 (70%). These data indicate that a part of DNA synthetic
      cells may result in apoptosis. The combination of immunohistochemistry, TEM and
      flow cytofluorometry to analyze DNA content and BrdU incorporation proved a
      useful tool for investigating the reconstituted thymus.

PMID- 9161693
TI  - Afferent migration of the Kurloff cells via lymphatics into the thymus of
      estradiol-treated guinea pigs.
AB  - The spatial distribution and migration of Kurloff cells containing PAS-positive
      large inclusion bodies in the thymus of estradiol-treated guinea pigs were
      histochemically studied by a combination of light and electron microscopy. Male
      guinea pigs were examined at various intervals from 7 days to 3 months after a
      single subcutaneous injection of estradiol. Differentiation of lymphatics from
      blood capillaries was performed by a 5'-nucleotidase (5'-Nase) staining method
      and the occurrence of Kurloff cells within 5'-Nase-positive lymphatics was
      confirmed by ultrastructural histochemistry. Several Kurloff cells first appeared
      at 7 days within lymphatics in the thymic capsule or interlobular connective
      tissues. At 12-15 days after estradiol administration, a lymphatic accumulation,
      a so-called "lymphatic center", was seen in the thymic septa even though few
      Kurloff cells were present within the thymic parenchyma. The "lymphatic center"
      contained many Kurloff cells located in its periphery and in the surrounding
      marginal sinus which communicated with the thymic interlobular lymphatics. At 21
      days after estradiol, Kurloff cells were preferentially accumulated along the
      corticomedullary junction extravascularly. Later the distribution was more
      diffuse. The conspicuous accumulation of Kurloff cells in the corticomedullary
      region could reflect an inability of Kurloff cells to use blood vessels as a
      route for migration. These findings strongly suggest the afferent migration of
      Kurloff cells into the thymus via lymphatics.

PMID- 9161692
TI  - Three-dimensional ultrastructure of the perivascular space in the rat thymus.
AB  - The overall architecture and structure of the perivascular space in the rat
      thymus were studied by light microscopy using silver-impregnated sections and
      sections stained immunohistochemically with anti-cytokeratin antibody, and by
      transmission and scanning electron microscopy (TEM and SEM). In silver
      impregnated sections, the perivascular space was delimited by a thin sheath of
      delicate argyrophilic fibers from the thymic parenchyma in the cortico-medullary
      region and medulla. This space was continuous with the septal connective tissue,
      indicating that this was the connective tissue compartment rather than with the
      epithelial compartment of the parenchyma. In the medulla, the perivascular space
      widened at places, where the argyrophilic sheath was often discontinuous and the
      boundary between the perivascular space and parenchyma was indistinct. Lymphatics
      were located in the perivascular space of the corticomedullary region and
      sometimes in the wide perivascular space of the medulla. The presence of a thymic
      epithelial sheath surrounding the perivascular space was confirmed by light
      microscopy of anti-cytokeratin antibody immunostained sections and by TEM. SEM
      observations revealed three-dimensionally that the epithelial sheath lined by
      collagen fibrillar (i.e., argyrophilic) layer form a rather continuous tubular
      structure in the cortico-medullary region, while it often interrupted in the
      medulla. These findings indicated that the perivascular space (i.e., the
      connective tissue compartment) is extensively open to the parenchyma (i.e., the
      epithelial compartment) in some portions of the medulla, where medullary
      lymphocytes are probably freely exposed to blood borne substances similar to the
      peripheral lymphoid tissues.

PMID- 9161694
TI  - Cross-reactivity of anti-yellowtail thymic lymphocyte monoclonal antibody (YeT-2)
      with lymphocytes from other fish species.
AB  - The monoclonal antibody YeT-2, generated in mice hyper-immunized with thymic
      lymphocytes of the yellowtail, Seriola quinqueradiata, reacts with the major
      population of peripheral blood lymphocytes, which might be putative T cells. In
      this study, we examined the cross-reactivity of YeT-2 with lymphocytes from
      various fish species. Flow cytometric analysis showed that YeT-2 reacts with
      69.8% lymphocytes in the thymus, 89.7% in the peripheral blood, 87.5% in the
      spleen, and 59.7% in the head-kidney. Among the six fish species examined, only
      the red sea bream, Pagrus major, which is included in the same suborder Percoidei
      with the yellowtail, showed the presence of YeT-2 positive cells. Electron
      microscopic studies revealed that YeT-2 positive cells in the peripheral blood of
      the red sea bream were lymphocytes or unidentified leucocytes. Thymic lymphocytes
      of the red sea bream were also immunocytochemically stained with YeT-2. The
      molecular weight of the YeT-2 cross-reacting antigen on blood cells from the red
      sea bream was identical with that from the yellowtail, which was identified at
      approximately 115 kDa. These results suggest that the monoclonal antibody YeT-2
      recognizes a conserved antigen on lymphocytes common to the red sea bream and
      yellowtail.

PMID- 9161695
TI  - High expression of heat shock protein 60 in follicular cells of Hashimoto's
      thyroiditis.
AB  - Heat shock protein 60 expression in the thyrocytes of Hashimoto's thyroiditis and
      Graves' disease was studied immunohistochemically. Thyrocytes of Hashimoto's
      thyroiditis showed high expression of heat shock protein 60 not only in tall
      eosinophilic-cells but also in low and flattened cells, although the former was
      stained with moderate to strong staining intensity and the latter weakly to
      moderately. Follicular cells around lymphoid cell follicles were stained more
      intensely, whereas cells apart from lymphoid cell follicles were stained weakly
      to moderately. In Graves' disease, only follicular cells around lymphoid cell
      follicles were stained with varying intensities. Since the pattern in all
      positive staining was granular, it was thought that heat shock protein 60
      overexpressed in thyrocytes located on mitochondria. To investigate the
      immunological role of overexpression of self heat shock protein 60 in the
      thyrocytes of Hashimoto's thyroiditis, gamma delta TCR+ T-cells in the tissue and
      the IgG class of anti-self heat shock protein 60 antibodies were studied. gamma
      delta TCR+ T-cells were detected among lymphoid cells scattered in
      interfollicular connective tissue. No difference in antibody level was seen among
      subjects with Hashimoto's thyroiditis, Graves' disease and normal subjects. Self
      heat shock protein 60 overexpression in the thyrocytes of Hashimoto's thyroiditis
      may play a disease-modifying role, although it does not influence the anti-self
      heat shock protein 60 antibody level.

PMID- 9161696
TI  - Effect of mizoribine on pulmonary lesions in MRL/lpr/lpr mice.
AB  - The present study was made to investigate the effect of mizoribine (MZR), an
      imidazole nucleoside immunosuppressant, on pulmonary lesions and immunological
      mode of action of MRL/lpr/lpr mice. Four-week-old female MRL/lpr/lpr mice were
      injected subcutaneously with 20 mg/kg body weight of MZR every other day. For
      control, mice were given phosphate-buffered saline (PBS) every other day. MZR
      caused the delay in the histological development of peribronchial and
      perivascular lymphocytic infiltrations in the lungs of MRL/lpr/lpr (MRL/lpr)
      mice. And then, MZR suppressed the number of immunoglobulin (Ig) (IgG and IgM)
      secreting B cells and anti-DNA-secreting B cells in the spleen of MRL/lpr/lpr
      mice. The above data indicate that MZR could be useful for the treatment of
      pulmonary lesions associated with autoimmune disorders such as systemic lupus
      erythematosus (SLE).

PMID- 9161697
TI  - Induction of immunotolerance in rats by intratesticular administration of an
      eicosapeptide of bovine S-antigen.
AB  - Immunization of albino LEW rats with a retinal soluble antigen (S-antigen)
      induces experimental autoimmune uveoretinitis (EAU) which shows clinical features
      resembling those of human uveitis. Several uveitogenic epitopes have been
      identified in the antigen. This study reports that an intratesticular injection
      of low doses of a uveitogenic eicosapeptide (P343-362) of S-antigen prior to
      immunization with the same peptide prevented the onset of EAU by inducing
      systemic tolerance, designated orchidic tolerance. Splenic lymphocytes of both
      CD4+ and CD8+ subsets from tolerized rats transferred orchidic tolerance to
      syngeneic recipients and protected them from subsequent EAU induction. Orchidic
      tolerance elicited by low antigen dosage was mediated, in part, by active
      suppression due to suppressor or regulatory cells. At high antigen doses,
      however, regulatory activity was reduced possibly due to the induction of anergy
      in regulatory cells, and EAU severity increased. The CD4+ regulatory T cells from
      tolerized rats showed enhanced expression of IL-4 mRNA compared with CD4+ cells
      from control rats. Increased immunoreactivity for IL-4, IL-10 and TGF-beta was
      observed in the spleen and lymph nodes of tolerized animals. The results suggest
      that orchidic tolerance induced by low doses of P343-362 is mediated in part by
      CD4+ regulatory cells secreting Th2 cytokines.

PMID- 9161698
TI  - EBT, a tryptophan contaminant associated with eosinophilia myalgia syndrome, is
      incorporated into proteins during translation as an amino acid analog.
AB  - The tryptophan dimer 1,1'-ethylidenebis[L-tryptophan] was identified as a
      contaminant of tryptophan preparations associated with Eosinophilia-Myalgia
      Syndrome. In this paper, we describe experiments examining the hypothesis that
      1,1'-ethylidenebis[L-tryptophan] acts as an amino acid analog replacing L
      tryptophan during the synthesis of proteins. We propose further that proteins
      containing 1,1'-ethylidenebis[L-tryptophan] are rejected in an autoimmune process
      identified clinically as Eosinophilia-Myalgia Syndrome. Rabbit reticulocyte
      lysates containing an estimated 1 microM L-tryptophan were used to assay the
      ability of 1,1'-ethylidenebis[L-tryptophan] to compete with 3H-L-tryptophan for
      incorporation into proteins translated from BMV RNA. 1,1'-Ethylidenebis[L
      tryptophan] in concentrations of 40, 80 and 110 microM reduced lysate 3H-L
      tryptophan incorporation to 81%, 76% and 75% of control incorporation obtained in
      the absence of 1,1'-ethylidenebis[L-tryptophan]. In the presence of 20 microM L
      tryptophan, 110 microM 1,1'-ethylidenebis[L-tryptophan] reduced 3H-L-tryptophan
      incorporation to 56% of control incorporation. In contrast, ethyl-L-tryptophan
      did not significantly reduce 3H-L-tryptophan incorporation. In the presence of
      110 microM 1,1'-ethylidenebis[L-tryptophan] and 20 microM L-tryptophan, 3H-L
      leucine incorporation was not significantly reduced compared to incorporation in
      the absence of 1,1'-ethylidenebis[L-tryptophan], demonstrating that proteins were
      translated to full length during elongation. These findings suggest that 1,1'
      ethylidenebis[L-tryptophan], but not ethyl-L-tryptophan, reduced 3H-L-tryptophan
      incorporation into proteins by substituting for L-tryptophan rather than by
      causing premature termination or significant slowing of nascent protein chains.

PMID- 9161699
TI  - An increased incidence of thyroid antibodies in patients with Turner's syndrome
      and their first degree relatives.
AB  - Previous studies have suggested that there may be a link between Turner's
      syndrome and autoimmunity. The numbers involved in these studies have tended to
      be small and few studies have included family members. This study has compared
      the incidence of thyroid antibodies in the serum of 60 patients with Turner'
      syndrome and 50 of their mothers with 127 controls. Total T4 and TSH levels were
      also measured. Of the 60 patients with Turner's syndrome 18 (30%) were positive
      for either thyroid peroxidase (TPO) and/or thyroglobulin antibodies. The peak
      incidence of thyroid antibodies occurred at 13 years of age. 11 (22%) of the
      mothers were also antibody positive. The incidence of thyroid antibodies was
      significantly higher in both the patients with Turner's Syndrome (30 vs 1.7% p <
      0.001) and their mothers (22 vs 6.6% p < 0.05) than in the control groups. The
      increased incidence of thyroid antibodies found in these patients and their
      mothers confirms that there is an association between Turner's Syndrome and
      autoimmunity. However unlike previous studies we found more patients were
      positive for thyroglobulin than TPO antibodies.

PMID- 9161700
TI  - CR1 density polymorphism and expression on erythrocytes of patients with systemic
      lupus erythematosus.
AB  - The present study investigated the expressed number of CR1 on erythrocytes (E) in
      relationship of the CR1 density genotype from 46 patients with systemic lupus
      erythematosus (SLE) and 47 healthy volunteers. The CR1 genotype was determined by
      a method based on polymerase chain reaction (PCR) amplification of the genomic
      DNA fragment of 1.8 kb separated by HindIII endonuclease digestion and agarose
      gel electrophoresis. Our data supported the earlier results that the number of
      binding sites/E for monoclonal anti-CR1 decreased among SLE patients compared
      with normal individuals having the same alleles for the CR1/E density. At the
      same time the novelty of our recent results was that the decreased expression of
      CR1 on E correlated significantly with kidney involvement in patients homozygous
      for the CR1/E high density allele (HH). These data suggest that the deficiency of
      the detectable number of CR1 on erythrocytes is acquired in this SLE population.

PMID- 9161701
TI  - Refolding kinetics of partially reduced and S-carboxymethylated trypsin
      subtilisin inhibitor from marine turtle eggwhite.
AB  - Three accessible disulphide bonds of basic trypsin-subtilisin inhibitor from
      marine turtle eggwhite have been reduced with 0.1M NaBH4 at 0 degree C under
      nitrogen atmosphere at pH9.8 and then S-carboxymethylated. The partially reduced
      inhibitor retains 80% of the native inhibitory activity towards trypsin and
      subtilisin. The S-carboxymethylated inhibitor undergoes slower refolding than the
      native inhibitor from its fully denatured and reduced state at pH 8.5 in the
      presence of oxidised and reduced glutathione. The refolding process was
      characterised by the attainment of the inhibitory activity towards trypsin and
      subtilisin. The values of the second order rate constant for the refolding
      reactions of the modified protein are 0.02 x 10(2)M-1sec1 and 0.033 x 10(2)M-1sec
      1 for its trypsin and subtilisin inhibiting domains and their energies of
      activation are 20.1 Kcal/mole and 24.6 Kcal/mole. The partially modified
      inhibitor does not regain complete inhibitory activity even after long incubation
      in the oxido-shuffling buffer. From the above findings it can be concluded that
      the three disulphide bonds of the native inhibitor are not essential for the
      inhibitory activity of the trypsin-subtilisin inhibitor but they help in the
      correct refolding of the inhibitor by forming transient disulphide bonds with the
      external disulphide reagents as well as with the internal sulphydryl groups.

PMID- 9161702
TI  - Elastin-derived peptide induces monocyte chemotaxis by increasing intracellular
      cyclic GMP level and activating cyclic GMP dependent protein kinase.
AB  - An elastin-derived peptide with an average molecular mass of 25 kDa was shown to
      induce monocyte chemotaxis at the optimal concentration of 10(-1) micrograms/ml.
      Homologous deactivation test showed that monocytes exposed to the elastin-derived
      peptide at 10(-1) micrograms/ml lost their chemotactic responsiveness when
      reexposed to the same stimulus. In conjunction with chemotactic response to the
      elastin-derived peptide, intracellular guanosine 3', 5'-monophosphate (cGMP)
      levels were enhanced but intracellular adenosine 3', 5'-monophosphate (cAMP)
      levels were not. The monocyte migration induced by the elastin-derived peptide
      was inhibited by cGMP dependent protein kinase (PKG) inhibitor, but not by cAMP
      dependent protein kinase inhibitor and protein kinase C inhibitor. These results
      suggest that the elastin-derived peptide induces monocyte chemotaxis by
      increasing the level of cGMP, followed by activating PKG.

PMID- 9161703
TI  - Over expression of inducible proteins in Escherichia coli by treatment with
      ethanol.
AB  - It is reported that ethanol enhances DNA synthesis in E. coli cells [Basu, T and
      Poddar, R. K. (1994), Folia. Microbiol. 39, 3-6]. This communication reports that
      during growth of E. coli in the presence of 5% v/v ethanol, the derepressed
      expression of the cytoplasmic enzymes beta-galactosidase and D-serine deaminase
      per cell increased approximately three fold, while that of the periplasmic enzyme
      alkaline phosphatase decreased approximately 40% compared to control cell levels.
      However, in cells transformed with the plasmid pSM 456, bearing phoA-lacZ fusion,
      the level of induced synthesis of the hybrid protein PhoA-LacZ, controlled by the
      phoA promoter, was elevated by 25% in the presence of 5% v/v ethanol. This result
      suggests that the induction of the alkaline phosphatase precursor has also been
      enhanced by the ethanol treatment, but the inhibition in the export of the
      precursor across the cytoplasmic membrane, by the influence of ethanol, may
      represent the reason for the deficient expression of active alkaline phosphatase.
      It is proposed that there is an ethanol-mediated increase in DNA synthesis,
      resulting in gene amplification, which may enhance the synthesis of inducible
      proteins in ethanol-treated cells.

PMID- 9161704
TI  - Characterization of a soluble IL-6 receptor alpha mutant C277D/H280I expressed in
      E.coli.
AB  - The pleiotropic cytokine interleukin-6(IL-6) triggers the formation of a high
      affinity receptor complex constituted by the ligand-binding subunit IL-6 receptor
      alpha (IL-6R alpha) and the signal transducer gp130. To construct the antagonist
      of IL-6, a DNA segment encoding the soluble human IL-6R alpha (shIL-6R alpha)
      mutant with two substitutions C277D/H280I was generated by overlap extension
      polymerase chain reaction. The DNA segment was then subcloned into vector pET-3b
      and expressed in E.coli at a high level. The refolded and purified recombinant
      protein, which was designated as DM650, exhibited an increased IL-6-binding
      capability by 8-fold. DM650 antagonized IL-6 perfectly, resulting in the growth
      inhibition of human myeloma AF-10 cells. DNA fragmentation assay proved that the
      growth of AF-10 cells was inhibited through the induction of apoptosis suppressed
      by IL-6.

PMID- 9161705
TI  - Primary structure of the smallest (6.4-kDa) subunit of human and bovine ubiquinol
      cytochrome c reductase deduced from cDNA sequences.
AB  - Amino acid sequences of the smallest subunit of human and bovine ubiquinol
      cytochrome c reductase were deduced from nucleotide sequence of recombinant cDNA
      clones isolated by screening the corresponding cDNA libraries. Both proteins were
      composed of 56 amino acids. They were 84% homologous to each other in the coding
      nucleotide sequences and 88% homologous in the amino acid sequences. Southern
      blot analysis with human DNA suggested the presence of a single gene coding for
      the protein. Northern blot of human mRNAs from different tissues confirmed the
      existence of a single species of transcript among the tissues but the human gene
      is highly expressed in bioenergetically active tissues like heart and skeletal
      muscle.

PMID- 9161707
TI  - Mutagenic and genotoxic activities of four pesticides: captan, foltaf,
      phosphamidon and furadan.
AB  - The mutagenic and genotoxic potential of four pesticides viz. captan, foltaf,
      phosphamidon and furadan was evaluated by the Ames mutagenicity assay and their
      DNA damaging ability on radiation repair defective E. coli K-12 strains
      respectively. The mutagenic spectrum revealed captan to be most mutagenic in the
      absence of metabolic activation, while the presence of S9 mix led to an
      attenuated mutagenic response. Foltaf, phosphamidon and furadan were detected as
      relatively weaker mutagens. A significant decrease in the survival of SOS
      defective mutants, recA, lexA and pol- of E. coli was observed as compared to
      their wild-type counterparts in the presence of the pesticides. The role of SOS
      repair genes gains further support from the Salmonella strains triggering the
      error-prone SOS response.

PMID- 9161706
TI  - Complete sequence of the UPP gene encoding uracil phosphoribosyltransferase from
      Mycobacterium bovis BCG.
AB  - The nucleotide sequence of a 799 bp fragment of Mycobacterium bovis BCG
      containing the putative upp gene that encodes a uracil phosphoribosyltransferase
      (UPRTase [EC 2.4.2.9]) has been determined. The upp gene of BCG has an open
      reading frame (ORF) of 621 bp (207 amino acids) starting with GTG (position 112)
      and ending with TGA (position 733), and its molecular mass was calculated to be
      21,864 Da. Comparative analyses of the deduced amino acid sequence of BCG UPRTase
      with the UPRTase of six bacterial genera revealed that 24% (50/211) of the
      residues are perfectly conserved and 32% (67/211) of the residues are well
      conserved.

PMID- 9161708
TI  - Encystment-specific mRNA is accumulated in the resting cysts of the ciliate
      Colpoda inflata.
AB  - From a random amplified polymorphism cDNA study using vegetative, precystic and
      mature resting cysts of the ciliate Colpoda inflata, a stage-specific fragment
      was isolated from the resting cyst cDNA population. This fragment was used as an
      encystment probe to study the corresponding mRNA expression during this
      eukaryotic cell differentiation process. This transcript is accumulated in the
      resting cyst of this ciliate, and it is the first time that accumulation of
      specific mRNA molecules associated with the ciliate cryptobiosis process is
      reported. The meaning of this stored mRNA in microbial cryptobiotic stages is
      discussed.

PMID- 9161709
TI  - Isolation and characterization of AFP-binding proteins from tumor and fetal human
      tissues.
AB  - The AFP receptor (rAFP) was discovered in embryonal and tumor tissues with a high
      level of proliferation. The AFP-binding protein (AFPbp) possibly containing the
      AFP-receptor (rAFP) was isolated from human embryos and human breast cancer
      tissue using affinity chromatography on an AFP-Sepharose column. The similarity
      of molecular weight, subunit composition, and immunological characteristics was
      shown for embryonal and tumor AFPbp using immunoblotting, gel-filtration, and
      PAAG electrophoresis. Judging from Superose-12 gel-filtration data, the protein
      molecular weight made up to 320-380 kDa. The presence of an IgG-binding site was
      detected in embryonal and tumor AFPbp by Western blot analysis.

PMID- 9161710
TI  - Differences in aldehyde oxidase activity in cytosolic preparations of human and
      monkey liver.
AB  - This study presents data showing individual differences in aldehyde oxidase
      activity in human and monkey liver cytosols. When assayed with benzaldehyde as a
      substrate, a significant inter-subject variation in the activity was found in the
      human liver preparations. When assayed with N1-methylnicotinamide as a substrate,
      the inter-subject variation of the activity was also observed, but to a lesser
      extent compared with that of the activity with benzaldehyde. Similarly,
      variations in aldehyde oxidase activity were found in the monkey liver
      preparations when assayed with benzaldehyde or N1-methylnicotinamide. The present
      study suggested that at least two isozymes of aldehyde oxidase exist in the human
      liver preparations.

PMID- 9161711
TI  - Regulation of the ferrochelatase gene expression during differentiation of mouse
      erythroleukemia cells.
AB  - Ferrochelatase [EC 4.99.1.1], the last step enzyme of heme biosynthesis, is
      transcribed from a single promoter. The enzyme is ubiquitously expressed in all
      cells, while the transcription is induced during erythroid differentiation. In a
      transient transfection assay, we identified two cis-acting elements involved in
      regulating the human ferrochelatase gene in mouse erythroleukemia (MEL) cells;
      one is the distal region (-108 to -95) for the basic expression in erythroid and
      non-erythroid cells, and the other is the proximal region (-80 to -72)
      corresponding to the induced expression during differentiation of
      dimethylsulfoxide-treated MEL cells. DNase I footprinting and gel mobility shift
      analyses revealed the presence of nuclear protein binding to the distal and the
      proximal regions, in both induced and uninduced MEL cells. These mean that two
      promoter regions play an important role in regulating the induced expression of
      ferrochelatase.

PMID- 9161712
TI  - Detection of polymorphic FGF receptor 1 mRNA in bovine lens epithelium by PCR.
AB  - The expression of FGFR 1, 2 and 3 but not FGFR 4 was detected in bovine lens
      epithelial cells. FGFR 1 expression of both the 2-lg and 3-lg forms was detected
      by a difference in the lengths of the PCR products. Furthermore, mRNA which
      included or excluded six nucleotides corresponding to two amino acids in the acid
      box region of FGFR 1 was detected by a difference in mobility of the homo- and
      hetero-duplex strands formed in the PCR reaction.

PMID- 9161714
TI  - Denaturation of uridine phosphorylase from Escherichia coli K-12 by guanidine
      hydrochloride.
AB  - Denaturation of uridine phosphorylase from Escherichia coli K-12 by guanidine
      hydrochloride results in red shift of the maximum in the protein fluorescence
      spectrum, dissociation of the hexameric enzyme molecule into monomers, and the
      loss of the enzymatic activity. The initial rate of the enzyme reactivation after
      the dilution of the enzyme preincubated with guanidine hydrochloride has the
      second order with respect to protein. It is assumed that the rate of the
      reactivation process is limited by the reassociation of monomers possessing low
      enzymatic activity to dimers followed by the rapid step of hexamer formation.

PMID- 9161713
TI  - Inhibition of DNA primase by sphingosine and its analogues parallels with their
      growth suppression of cultured human leukemic cells.
AB  - Sphingosine is a potent inhibitor of a mammalian DNA primase in vitro (Simbulan
      et al., Biochemistry 33, 9007-9012, 1994). Here we measured the inhibition of DNA
      primase in vitro by 9 sphingosine-analogues with respect to RNA primer synthesis
      and DNA primase-dependent DNA synthesis, and their potencies of inhibition in
      vitro were compared with their in vivo effects on human leukemic cells.
      Sphingosine, phytosphingosine and N, N-dimethylsphingosine strongly inhibited the
      activity of purified calf thymus DNA primase, and also inhibited the growth of
      human leukemic cell line HL-60, exerting strong cytotoxicity. Dihydrosphingosine
      and cis-sphingosine, which showed more subtle inhibition of DNA primase in vitro,
      moderately inhibited the cell growth in vivo and caused cell death. In contrast,
      N-acyl-, N-octyl-, and N-acetylsphingosine (ceramides) showing little inhibition
      of DNA primase suppressed cell growth only slightly. HL 60 cell was arrested at
      Go/G1 phase by exogenously added sphingosine. From these results, it is suggested
      that DNA primase is one of targets of sphingosine, an effector molecule in
      apoptosis.

PMID- 9161716
TI  - D-glucose metabolism in dimethyl suberimidate-treated tumoral pancreatic islet
      cells.
AB  - After protein cross-linking by dimethyl suberimidate, tumoral insulin-producing
      cells of the RINm5F line were either exposed to digitonin for measurement of
      hexokinase activity in the resulting cell pellet and supernatant, or incubated in
      the presence of D-[5-3H]glucose, D-[U-14C]glucose or L-[U-14C]glutamine to assess
      the metabolism of these nutrients. After digitonin treatment, the activity of
      hexokinase recovered in the cell pellet was about 40% higher in cross-linked than
      control RINm5F cells. Although failing to affect the metabolism of L-[U
      14C]glutamine, and severely decreasing the oxidation of D-[U-14C]glucose, the
      cross-linking of proteins accentuated the increase in D-[5-3H]glucose utilization
      and D-[U-14C]glucose conversion to acidic metabolites resulting from a rise in
      hexose concentration from 2.8 to 16.7 mM. The latter change represents a mirror
      image of that previously found in cross-linked pancreatic islets. Taking into
      account the vastly different participation of glucokinase to hexose
      phosphorylation in RINm5F cells and normal islet cells, the present findings
      further support, therefore, the regulatory role of protein-to-protein interaction
      in the control of glucokinase catalytic activity in these fuel-sensing cells.

PMID- 9161715
TI  - Bovine kidney low molecular weight acid phosphatase: FMN-dependent kinetics.
AB  - A low molecular weight bovine kidney acid phosphatase, electrophoretically
      homogeneous and with a relative molecular mass of 17.8 kDa, was used in this
      work. Among the various substrates tested, FMN was found to be the most
      effective, at pH 7.0. Distinct activation energy values were obtained for p
      nitrophenyl phosphate- (45.44 kJ mol-1) and flavin mononucleotide- (28.60 kJ mol
      1) hydrolysis reactions. The FMN hydrolysis was strongly inhibited by Cu2 and
      pCMB, but activated by guanosine. Pyridoxal-phosphate and vanadate were
      competitive inhibitors for the FMN-dependent reaction.

PMID- 9161717
TI  - Modulation of sperm acrosomal exocytosis by guanyl nucleotides and G-protein
      modifier agents.
AB  - Mammalian sperm must undergo an exocytotic event during fertilization, the
      acrosome reaction (AR). This process is specifically induced by egg-surface
      glycoproteins and it involves guanine nucleotide binding proteins (G-proteins).
      Neoglycoproteins (NGP) with mannose or N-acetylglucosamine residues has been
      demonstrated to induce the AR in human sperm. Activators of G-proteins, like GTP
      gamma S, GppNHp, mastoparan and AlF4- were capable of inducing the AR, while
      other nucleotides or analogues did not. When sperm were preincubated with these
      agents and then with NGPs, only the G-protein inhibitor GDP beta S decreased the
      AR rate. The preincubation of sperm with Pertussis toxin resulted in the
      inhibition of NGP-induced AR, while no effect was observed with cholera toxin.
      Results indicate that direct activation of G-proteins is sufficient to elicit the
      AR, and the induction of the AR in human sperm is mediated by N
      acetylglucosaminyl and mannosyl binding sites involving PTx-sensitive G-proteins
      similar to the induction by zona pellucida glycoproteins.

PMID- 9161718
TI  - High salt and solvent induced Z-conformation in native calf thymus DNA.
AB  - The Z-DNA forming potentiality of native calf thymus DNA using spectrophotometric
      measurements and diethyl pyrocarbonate reactivity have been investigated. The Z
      value was evaluated from absorbance ratio for B- and Z-DNA and compared with the
      values obtained for native DNA. The results suggest that native DNA undergoes B-
      to Z-/Z-analogous transition to an extent of 20 per cent under constraint
      conditions. Possible Z-DNA formation was also characterized by hyper-reactivity
      of native DNA towards diethyl pyrocarbonate in aqueous solvent. The thermal
      melting profile of native and modified DNA and nuclease S1 digestibility data, in
      addition, reflects B- to Z-/Z-analogous transition in native DNA.

PMID- 9161719
TI  - Interaction of interferon-gamma and epidermal growth factor in the regulation of
      nitric oxide production and cellular proliferation in a cultured murine mammary
      cell line, COMMA-D.
AB  - The regulation of nitric oxide synthase (NOS) activity and gene expression by
      cytokines and growth factors has been studied using the murine mammary epithelial
      cell line, COMMA-D. NOS activity was stimulated by exposure to interferon-gamma
      (IFN-gamma) and could be further stimulated by tumour necrosis factor-alpha (TNF
      alpha) and epidermal growth factor (EGF) although neither was affective alone.
      The maximal activity observed in the presence of IFN-gamma and EGF was not
      affected by the order in which cells were exposed. Messenger RNA levels for the
      inducible NOS isoform were increased by IFN-gamma and TNF-alpha in a manner
      consistent with the elevation of NOS activity. EGF also stimulated thymidine
      incorporation into DNA which was attenuated by coexposure with IFN-gamma in a
      manner that appeared to be largely NO-independent.

PMID- 9161720
TI  - The structural and functional essentiality of the N-terminal alpha-helix in the
      phospholipase A2 of the Taiwan banded krait.
AB  - In order to identify the structural and functional essentiality of the N-terminal
      alpha-helix of Bungarus multicinctus PLA2 for its enzymatic activity, comparative
      studies of the biochemical properties of native and recombinant PLA2 were made.
      It was found that the appearance of a Met residue preceding the N-terminus Asn-1
      of the recombinant protein appreciably affected PLA2 activity and the hydrophobic
      character of the ANS-binding site. Additionally, the charged state and the
      hydrophobicity of the molecular surface changed as well. However, removal of the
      N-terminal Met-1 from the recombinant PLA2 resulted in the production of a fully
      active PLA2, whose biochemical properties were indistinguishable from those of
      the native enzyme. These observations, together with the findings that the
      helical wheel plot of the N-terminal alpha-helix showed distinct hydrophobic and
      hydrophilic faces and that the ANS-binding site was the active site of PLA2
      enzymes, suggest that the hydrophobic face of the N-terminal alpha-helix in
      native PLA2 should be in the interior of the enzyme molecule for binding with ANS
      and the phospholipid/substrate.

PMID- 9161721
TI  - TsTX-VII, a new toxin from Tityus serrulatus scorpion venom able to induce the
      release of neurotransmitters from rat brain synaptosomes not blocked by
      tetrodotoxin.
AB  - A procedure for the isolation of the toxin Tityustoxin VII (TsTX-VII) from Tityus
      serrulatus scorpion venom and its biochemical characterization is reported. This
      protein has a M(r) = 6,700-6,800, eight half-cystine residues accounting for four
      disulfide bridges and no His. Its N-terminal sequence GHZGYGS ... characterizes
      it as a new toxin, able to release glutamic acid and gamma aminobutyric acid from
      rat brain synaptosomes "in vitro". This release was also induced by the whole
      venom. Tetrodotoxin however blocked the effect of the whole venom but not that of
      TsTX-VII, thus suggesting that the releasing mechanism by TsTX-VII does not
      involve Na+ but perhaps K+ or Ca++ channels.

PMID- 9161722
TI  - Kinetic study of the oxidation of 4-hydroxyanisole catalyzed by tyrosinase.
AB  - Despite the importance of the substrate 4-hydroxyanisole in melanoma therapy, the
      kinetics of its oxidation catalyzed by tyrosinase has never been properly
      characterized. This approach is reported here for the first time. The
      applicability to 4-hydroxyanisole of the reaction mechanism of tyrosinase
      previously proposed for other monophenols has been corroborated. The Michaelis
      constant for the oxidation of 4-hydroxyanisole catalyzed by mushroom tyrosinase
      was (62 +/- 1.5) microM at pH 7 and increased when the pH decreased, reaching a
      value of (195 +/- 5) microM at pH 5.5. However the maximum steady-state rate,
      whose value was (0.54 +/- 0.01) microM/min, did not change with the pH. The
      apparent catalytic constant was (184 +/- 5) s-1, around twenty three times higher
      than that previously described for L-tyrosine (8 s-1).

PMID- 9161723
TI  - A confocal microscopic analysis of galaninergic hyperinnervation of cholinergic
      basal forebrain neurons in Alzheimer's disease.
AB  - The galanin (GAL) containing peptide fiber system innervates the basal forebrain
      and has been shown to hyperinnervate remaining cholinergic neurons in Alzheimer's
      disease (AD). GAL modulates the release of acetylcholine and, therefore, may
      depress this neurotransmitter in surviving cholinergic basal forebrain (CBF)
      neurons in AD. The aim of this study was to identify putative synaptic contacts
      between GAL immunoreactive processes and CBF neurons and evaluate whether these
      processes hypertrophy in AD patients. We observed by confocal laser microscopy a
      hyperinnervation of GAL-containing fibers in both AD and Parkinson's disease
      patients with concurrent AD (PD/AD). Galaninergic fibers were often seen in
      direct apposition to remaining CBF neurons and enwrapped cholinergic cell soma
      and dendrites. Our results demonstrate that GAL-containing fibers are in direct
      apposition to CBF neurons in normal-aged humans and that this phenotype is
      enhanced in AD and PD/AD, suggesting that direct synaptic contacts occur between
      GAL-containing fibers and CBF neurons. Because GAL can modulate acetylcholine
      release from cholinergic neurons, hyperinnervation of GAL fibers in AD and PD/AD
      patients may further decrease release of acetylcholine from remaining CBF
      neurons. We propose that therapies based solely on acetylcholinesterase
      inhibitors may be insufficient to effectively increase cortical levels of
      acetylcholine.

PMID- 9161724
TI  - Characterization of neural cell lines derived from SV40 large T-induced primitive
      neuroectodermal tumors.
AB  - We recently reported intriguing properties of neural tumors generated by
      retrovirus-mediated transfer of the SV40 large T antigen into fetal rat brain
      transplants. Histopathologically, these neoplasms displayed characteristic
      features of primitive neuroectodermal tumors (PNET) and exhibited a striking
      potential for migration into the host brain. In the present study, four cell
      lines were derived from these PNETs and characterized. Two lines with an immature
      phenotype expressed the embryonal form of the neural cell adhesion molecule and
      nestin. They showed spheroid formation and delicate cell processes. The remaining
      cell lines had a flat, epitheloid appearance and were immunoreactive for
      synaptophysin, neurofilament proteins and glial fibrillary acidic protein. These
      cells constitute valuable tools to study the cellular origin(s) and molecular
      basis of PNETs, differentiation of neural progenitors and tumor cell migration in
      the brain.

PMID- 9161725
TI  - The role of macrophages in Wallerian degeneration.
AB  - The present review focuses on macrophage properties in Wallerian degeneration.
      The identification of hematogenous phagocytes, the involvement of cell surface
      receptors and soluble factors, the state of activation during myelin removal and
      the signals and factors leading to macrophage recruitment into degenerating
      peripheral nerves after nerve transection are reviewed. The main effector cells
      in Wallerian degeneration are hematogenous phagocytes. Resident macrophages and
      Schwann cells play a minor role in myelin removal. The macrophage complement
      receptor type 3 is the main surface receptor involved in myelin recognition and
      uptake. The signals leading to macrophage recruitment are heterogenous and not
      yet defined in detail. Degenerating myelin and axons are suggested to
      participate. The relevance of these findings for immune-mediated demyelination
      are discussed since the definition of the role of macrophages might lead to a
      better understanding of the pathogenesis of demyelination.

PMID- 9161726
TI  - Recent advances in the molecular characterization of childhood brain tumors.

PMID- 9161727
TI  - A molecular genetic model of astrocytoma histopathology.
AB  - As the molecular events responsible for astrocytoma formation and progression are
      being clarified, it is becoming possible to correlate these alterations with the
      specific histopathological and biological features of astrocytoma, anaplastic
      astrocytoma and glioblastoma multiforme. In WHO grade II astrocytomas, autocrine
      stimulation by the plateletderived growth factor system coupled with inactivation
      of the p53 gene may lead to a growth stimulus in the face of decreased cell death
      with slow net growth ensuing. Such cells would also have defective responses to
      DNA damage and impaired DNA repair, setting the stage for future malignant
      change. Such biological scenarios recapitulate many of the clinicopathological
      features of WHO grade II astrocytomas. Anaplastic astrocytomas further display
      release of a critical cell cycle brake that involves the CDKN2/p16, RB and CDK4
      genes. This results in mitoses seen histologically; clinically, there is more
      conspicuous, rapid growth. Finally, glioblastomas may emerge from the
      microenvironmental outgrowth of more malignant clones in a complex vicious cycle
      that involves necrosis, hypoxia, growth factor release, angiogenesis and clonal
      selection; growth signals mediated by activation of epidermal growth factor
      receptors may precipitate glioblastomas. It is clear as well that glioblastoma
      multiforme can arise via a number of independent genetic pathways, although the
      clinical significance of these distinctions remains unclear.

PMID- 9161728
TI  - Primitive neuroectodermal tumors of the central nervous system.
AB  - Controversial issues relating to the pathobiology and classification of central
      nervous system primitive neuroectodermal tumors (PNETs) have plagued
      neuropathologists for more than 70 years. Hypotheses advanced in the mid-1920's
      have remained as fixed concepts in contemporary literature, largely consequent to
      repetitious support by a small number of neuropathologists despite a growing body
      of information discrediting these ideas from neuroembryologists, oncologists,
      neuroscientists and pathologists. Attention has largely focused upon PNETs
      arising in the cerebellum (commonly known as medulloblastomas ([MBs]), because
      about 80% of central nervous system (CNS) PNETs originate in this site. It has
      been asserted that the 20% which do not are biologically different, although most
      individuals agree that the histological features of PNETs that occur in different
      sites throughout the CNS are indistinguishable from those growing in the
      cerebellum. The historical aspects of this controversy are examined in the face
      of evidence that there is, in fact, a unique class of CNS tumors which should
      appropriately be regarded as primitive neuroectodermal in nature. Specifically, a
      number of different approaches to the problem have yielded data supporting this
      hypothesis. These approaches include the identification of patterns of expression
      among a variety of cellular antigens (demonstrated by the use of
      immunopathological techniques), molecular analyses of cell lines derived from
      these tumors, experimental production of PNETs and molecular genetic analyses.
      Differences of opinion among surgeons, oncologists and radiotherapists are
      typically resolved by conducting cooperative studies of patients with these
      tumors who are diagnosed and treated at multiple centers.

PMID- 9161729
TI  - Classification and grading of low-grade astrocytic tumors in children.
AB  - This article reviews current perspectives in the classification and grading of
      astrocytomas in children and calls attention to several histologically distinct
      groups of low-grade tumors that characteristically arise during childhood.
      Recognition of these tumors and the range of histological features that they may
      exhibit is essential for making rational assessments regarding their expected
      behavior and, more importantly, for guiding therapeutic intervention. For
      example, pleomorphic xanthoastrocytoma, which may exhibit "anaplastic" features,
      generally carries a relatively favorable prognosis and should not be classified
      with other high-grade gliomas, such as anaplastic astrocytoma and glioblastoma
      multiforme. Similarly, the finding of anaplastic features, such as vascular
      proliferation or necrosis, in pilocytic astrocytomas does not automatically
      portend the unfavorable prognosis that such features would imply for "diffuse"
      astrocytomas. Increased appreciation of the morphological diversity of
      astrocytomas in children should help to improve the management of children with
      low-grade astrocytic tumors by avoiding potentially dangerous overtreatment of
      otherwise indolent lesions.

PMID- 9161730
TI  - Optic chiasmatic-hypothalamic glioma.
AB  - Optic chiasmatic-hypothalamic gliomas (OCHGs) have been considered benign tumors
      and self-limiting in growth potential because of their histological appearance.
      Unfortunately, most clinical series have reported significant morbidity and
      mortality especially with the more extensive, posteriorly positioned tumors. The
      biological behavior of OCHGs is age-dependent, with patients younger than five
      years and older than 20 years typically having tumors that exhibit aggressive
      growth. There are no specific pathological features to help differentiate the
      clinical behavior of such tumors. The emergence of modern imaging techniques,
      including magnetic resonance imaging (MRI), has facilitated the monitoring of the
      natural history of the disease and the determination of the effects of therapy.
      Most patients with OCHGs survive for many years. While the natural history of an
      OCHG for any individual may be indeterminate, enough data are now available from
      large series to make recommendations for treatment. Our current treatment policy
      for patients with OCHGs in the context of NF-I without visual failure is a
      conservative one involving CSF shunting for hydrocephalus if present and medical
      therapy for endocrinologic dysfunction. Patients with or without NF-I with visual
      deterioration or progressive neurological deficits and a rapidly expanding
      suprasellar mass lesion are treated surgically. After tumor resection, patients
      whose vision is significantly compromised or who show progression of their
      disease on serial neuroimaging scans receive chemotherapy. If chemotherapy proves
      ineffective in disease stabilization, then considerations of radiation therapy
      are given to children over five years old.

PMID- 9161731
TI  - The molecular biology of ependymomas.
AB  - Intracranial ependymomas are the third most common primary brain tumor in the
      pediatric population. Although an anaplastic variant is recognized, numerous
      studies examining the prognostic implications of histological features, such as
      necrosis, endothelial proliferation and mitoses, have yielded contradictory
      results. In order to improve outcome prediction in affected patients and to
      refine therapeutic decision-making, there is a strong need for identifying
      relevant biological correlates of tumor behavior. The molecular biology of tumors
      is a rapidly expanding field and includes investigations into cytogenetics,
      oncogenes, growth factors, growth factor receptors, hormonal receptors,
      proliferation markers, apoptosis, cell cycle genes and cell adhesion molecules,
      as well as factors potentially related to therapeutic resistance, such as the
      multidrug resistance gene. The molecular biology of astrocytic tumors in adults
      has been the subject of many studies; however, relatively few studies have been
      focused on ependymomas. Herein we review potential oncological markers in
      ependymomas that have been identified to date and highlight the limitations of
      our current knowledge as a basis for defining areas for future investigation.

PMID- 9161732
TI  - Neurofibromatosis 1 and 2.
AB  - Neurofibromatosis (NF) 1 and 2 are multisystem disorders associated with a
      variety of neoplastic and non-neoplastic manifestations that typically progress
      in severity during the lifetime of the affected patient. The importance of
      appropriately diagnosing these disorders stems from the fact that the natural
      history of an associated neoplasm, such as a peripheral nerve tumor or an optic
      glioma, may be significantly different depending on whether or not the lesion
      arises in a person with NF. In addition, the indications for therapeutic
      intervention, hierarchy of treatment options and long-term management goals may
      differ substantially for patients with NF-related versus sporadic tumors.
      Finally, recognition of the diagnosis comprises an essential step for providing
      appropriate multidisciplinary evaluation and counseling to affected patients and
      their families. This article addresses the principal manifestations of these
      disorders and provides a contemporary review of the diagnostic and therapeutic
      issues that arise in children with NF1 and NF2.

PMID- 9161733
TI  - October 1996--rapidly progressive weakness.
AB  - One week after a flu-like illness, a 51-year-old woman developed rapidly
      progressive weakness. Within three weeks, she required mechanical ventilation. A
      neurological exam revealed severe motor involvement with normal sensory findings
      confirmed by nerve conduction studies. Five days after intubation a catastrophic
      brain hemorrhage occurred. Autopsy showed severe loss of axons in the motor roots
      with periaxonal macrophages and no lymphocytes. These findings are typical of
      acute motor axonal neuropathy, which is rare in the United States.

PMID- 9161734
TI  - November 1996--premature baby with lethargy and coma.
AB  - A premature male baby (28 weeks gestational age) was delivered by Cesarean
      section and required ventilation for respiratory distress syndrome during the
      first postnatal week. Four weeks postnatally, he had an episode of transient
      renal failure followed by lethargy leading to coma. Ultrasound changes were
      interpreted as intraventricular hemorrhage, grade 2. The baby died 31 days after
      birth. Autopsy showed bilateral thrombosis of the deep cerebral veins.

PMID- 9161735
TI  - December 1996--cervicomedullary tumor.
AB  - A cervicomedullary tumor in a 22-month-old female with an eight-month history of
      symptoms showed the histological features of a pilocytic astrocytoma but had many
      areas of palisading cells identical to those described in polar spongioblastomas.
      The tumor recurred 18 months later and showed predominately pilocytic features.
      The case is used to discuss polar spongioblastomas and tumors which can
      histologically simulate them.

PMID- 9161736
TI  - Novel targets of pain modulation in anaesthesia: preventing painful memories.

PMID- 9161737
TI  - Opioids and seizures.

PMID- 9161738
TI  - Haemodynamic effects of mechanical peritoneal retraction during laparoscopic
      cholecystectomy.
AB  - PURPOSE: Abdominal wall retraction (AWR) was recently proposed as an alternative
      for CO2 pneumoperitoneum. In this study we evaluated the cardiorespiratory
      effects of AWR during laparoscopic cholecystectomy. METHODS: Fifteen patients
      were studied during laparoscopic cholecystectomy using AWR. Monitoring included
      heart rate (HR), mean arterial pressure (MAP), pulse oxymetry (SpO2), end-tidal
      CO2 (PETCO2) minute ventilation, and peak inspiratory pressure (PIP). Using
      transoesophageal echocardiography, the transgastric short axis view was obtained
      to derive the end-diastolic area (EDA), the end-systolic area (ESA), and the
      ejection fraction (EF). These parameters were measured at predetermined periods:
      1) five minutes after anaesthetic induction, 2) five minutes after AWR insertion,
      3) 15 min after AWR insertion, and 4) after the end of surgery. RESULTS: No
      change in any measured parameter was observed over time in the AWR group except
      for an increase in MAP (P < 0.05) after AWR insertion. There were no changes in
      EDA, ESA and EF during the study, reflecting stable global cardiac function. In
      addition, no embolic episodes were observed during surgery. CONCLUSION: Our
      results demonstrate that the use of gasless abdominal distention for laparoscopic
      cholecystectomy results in a stable haemodynamic profile in healthy patients
      without cardiac disease, except for a brief increase in MAP after the AWR
      insertion. The advantages of AWR over conventional pneumoperitoneum should be
      confirmed in higher risk patients in a prospective, randomized study.

PMID- 9161739
TI  - Sorbitol 2.5% mannitol 0.54% irrigation solution for hysteroscopic endometrial
      ablation surgery.
AB  - PURPOSE: To determine if systemic absorption of sorbitol 2.5%/mannitol 0.54%
      irrigation solution (165 mosm.L-1) during hysteroscopic endometrial ablation with
      diathermy is associated with hyponatraemia and hypoosmolality. METHODS: In 35 day
      surgery patients in a university hospital we measured baseline preoperative
      variables: serum sodium and creatinine concentrations and osmolality,
      haematocrit, haemoglobin, urine osmolality and sodium concentration, and weight.
      Fractional excretion of sodium (FENa) was calculated. The same observations were
      obtained postoperatively before discharge (one hour post resection). Volumes of
      intraoperative fluid irrigation intravasation and perioperative intravenous fluid
      absorption (lactated Ringer's solution) were estimated clinically (volumetric).
      RESULTS: The mean (+/-SD) serum sodium concentration preoperatively was 140.3 +/-
      2.4 mmol.L-1; and postoperatively, 139.7 +/- 2.2 mmol.L-1 (P = NS). The serum
      osmolality decreased from 285.4 +/- 4.5 to 282.6 +/- 4.1 mmol.kg-1 (P < 0.001).
      The mean volume of intravasated irrigation fluid was 26.4 ml (range 0-300).
      During the same time, the FENa increased from 0.57% to 0.79% (P < 0.001).
      CONCLUSION: In these patients, closely and continuously observed for imbalance
      between infused and collected irrigation fluid, these was no clinical evidence
      for hyponatraemic hypoosmolality. However, there was a small 1% +/- 1.5% (mean +/
      SD; range -3.4 to 3.6%) decrease in plasma osmolality despite adequate blood
      volumes as shown by urinary sodium indices.

PMID- 9161740
TI  - Postoperative analgesia with i.v. propacetamol and ketoprofen combination after
      disc surgery.
AB  - PURPOSE: The concept of balanced analgesia suggests that a combination of
      analgesic drugs may enhance analgesia and reduce side effects after surgery. This
      study evaluated the effect of the combination of propacetamol (Prodafalgan) and
      ketoprofen (Profenid) after surgery of a herniated disc of the lumbar spine.
      METHODS: After randomization, 60 patients received: placebo (group 1); 2 g
      propacetamol (group 2); 50 mg ketoproten (group 3); or a combination of 2 g
      propacetamol and 50 mg ketoprofen (group 4). Drugs were administered every six
      hours for two days after surgery. The patients used morphine with patient
      controlled analgesia pumps (bolus 1 mg; lock out time 10 min) and were evaluated
      with a visual analogue scale (VAS) at rest and movement every six hours for two
      days. Side effects were noted. RESULTS: The patient characteristics and surgery
      were identical for each of the four groups. The VAS scores throughout the study
      were lower in group 4 than in groups 1, 2 and 3 both at rest (P < 0.05) and on
      movement (P < 0.01). The cumulative dose of morphine at 48 hr was lower in group
      4 than in group 1 (23.4 +/- 5 mg vs. 58.9 +/- 9 mg; P < 0.01) or group 2 (23.4 +/
      5 mg vs 43.4 +/- 6.6 mg; P < 0.05) and similar to that in group 3 (34.2 +/- 4.5
      mg). The incidence of side effects was similar in all groups. CONCLUSION: The
      combination of propacetamol and ketoprofen reduced pain scores both at rest and
      on movement. The drug combination did not reduce the morphine consumption and
      incidence of side effects.

PMID- 9161741
TI  - Detecting wakefulness in anaesthetised children.
AB  - PURPOSE: To investigate the suitability of the isolated forearm technique in
      detecting wakefulness in children aged 8 to 16 yr. METHODS: Forty-one healthy
      English speaking children were enrolled. Following intravenous induction of
      anaesthesia with 5-7 mg.kg-1 thiopentone iv, but before administration of 1-1.5
      mg.kg-1 succinylcholine a pneumatic tourniquet was inflated to 50 mmHg above
      systolic pressure in order to isolate the non-cannulated forearm. Thereafter,
      anaesthesia was maintained with halothane 1.5-2.5% in nitrous oxide and oxygen.
      Following the muscle relaxant the patient was instructed to move the unparalyzed
      arm. Movement was checked at 30 sec intervals and if present on command,
      identified as wakefulness. RESULTS: Movement of the isolated forearm to command
      was observed in 19.5% of children. The youngest child to respond was five years
      old. CONCLUSION: The isolated forearm technique can be used to detect wakefulness
      during and immediately following tracheal intubation in children from the age of
      five years.

PMID- 9161742
TI  - Granisetron reduces postoperative nausea and vomiting throughout menstrual cycle.
AB  - PURPOSE: The incidence of postoperative nausea and vomiting (PONV) is influenced
      by menstruation. This study was undertaken to assess the efficacy of granisetron,
      a selective 5-hydroxytryptamine type 3 receptor antagonist, for preventing PONV
      in patients during two different phases of menstrual cycle. METHODS: One hundred
      twenty female patients undergoing general anaesthesia for major gynaecological
      surgery were divided according to the phase of menstrual cycle into two groups:
      day one to eight (menstrual) and day nine to end of the cycle (non-menstrual)
      groups. In a randomized, double-blind manner, the patients received placebo
      (saline) or 40 micrograms.kg-1 granisetron i.v. immediately before the induction
      of anaesthesia. All patients received a standardized general and epidural
      anaesthesia and epidural morphine plus bupivacaine for postoperative analgesia.
      The incidence of PONV and other adverse events was recorded during the first 24
      hr after anaesthesia. RESULTS: The treatment groups were similar with respect to
      patient demographics, types of surgery, anaesthetics administered and analgesics
      used postoperatively. The incidence of PONV was 72% and 32% in patients during
      menstruation receiving placebo or granisetron (P < 0.05), and was 46% and 20% in
      those during non-menstruation, respectively (P < 0.05). No differences in the
      incidence of other adverse events were observed among the groups. CONCLUSION:
      Granisetron was effective in reducing the incidence of PONV in both phases of the
      menstrual cycle studied.

PMID- 9161743
TI  - A comparison of simple tests to distinguish cerebrospinal fluid from saline.
AB  - PURPOSE: This prospective study was undertaken to determine if anesthesiologists
      of different levels of training, using simple tests, can distinguish
      cerebrospinal fluid (CSF) from saline. METHODS: Thirty-two anaesthetists, divided
      into four groups, dependent upon levels of training, participated in the study.
      Each was asked to distinguish saline from an artificial CSF solution using four
      different tests: tactile temperature, glucose strip, pH strip, and turbidity when
      mixed with thiopental. RESULTS: Participants identified cerebrospinal fluid
      correctly with 84% accuracy using the temperature test, 97% using the glucose
      test, 91% using the pH test, and 50% using the thiopentone test. More than half
      of the participants guessed while using the thiopentone test, and those who did
      not guess were only 47% accurate. CONCLUSION: Level of training made no
      difference in distinguishing CSF from saline. No one test was 100% reliable.
      Clinical utility of the thiopentone test appears to be limited. The temperature,
      glucose, and pH tests, when used together, appear to be a useful way of
      distinguishing CSF from saline.

PMID- 9161744
TI  - Fasciculations, myalgia and biochemical changes following succinylcholine with
      atracurium and lidocaine pretreatment.
AB  - PURPOSE: To determine the attenuation in the incidence of myalgia, fasciculations
      and changes in serum potassium and creatinine kinase concentrations when
      atracurium and lidocaine were used in combination and separately as pretreatment
      before succinylcholine. METHODS: In a prospective, double blind randomized study,
      80 ASA 1 patients 20-50 yr were assigned to one of four groups. Anaesthesia was
      induced with thiopentone and fentanyl. Group C received placebo pretreatment
      before 1.5 mg.kg-1 succinylcholine; Group A 0.05 mg.kg-1 atracurium three minutes
      before; Group L, 1.5 mg.kg-1 lidocaine 30 sec before; and group AL both
      atracurium and lidocaine. Serum potassium five minutes after succinylcholine, and
      creatinine kinase 24 hr after operation were measured and the increases from
      preinduction values were compared. Fasciculations and postoperative myalgia at 24
      and 48 hr were recorded. Patients received iv meperidine or po paracetamol for
      postoperative analgesia. RESULTS: The increase in serum potassium concentration
      (0.36 +/- 0.23 mEq.l-1) was not attenuated by any regimen (P < 0.05). The
      incidence of fasciculations (P < 0.05) and the increase in creatinine kinase (P <
      0.01) was less in the atracurium (40%; 20.93 IU.l-1) and atracurium-lidocaine
      (30%; 22.85 IU.l-1) than in the lidocaine (85%; 45.01 IU.l-1) and control (100%;
      56.5 IU.l-1) groups. Postoperative myalgia on Days 1 and 2 was lowest (P < 0.05)
      in the atracurium-lidocaine group (5%; 0%) followed by the atracurium (35%; 25%)
      and lidocaine (30%; 35%) groups and highest in the control (75%; 65%).
      CONCLUSION: Atracurium and lidocaine individually reduce postoperative myalgia,
      with further decrease occurring when used together.

PMID- 9161745
TI  - Does the method of payment affect anaesthetic practice? An evaluation of an
      alternate payment plan.
AB  - PURPOSE: To test the null hypothesis that the method of physician payment does
      not influence the practice of anaesthesia. METHODS: Retrospective cohort study of
      anaesthetists before (Jan-June, 1994) and after (Jan-June, 1995) departure from
      fee-for-service practice into an alternate funding arrangement (AFP). Another
      group of physicians was studied as a concurrent control. Case numbers, induction
      times, cancellation rates, and operating hours for the department, recorded by
      third parties, were compared before and after AFP implementation. Using index
      procedures, details of individual patient decisions made by anaesthetists were
      compared for the two study periods, and between subscribing and non-subscribing
      physicians. RESULTS: Implementation of AFP resulted in a modest reduction in case
      numbers (7.2%) offset by an increase (5.7%) in the average case duration. Net
      change in time dedicated to clinical service (2% per physician) is
      inconsequential to the academic mission of the department. There was no change in
      cancellation rate and the use of invasive monitors was unchanged. An increase in
      the use of regional anaesthesia occurred but, since a similar increase occurred
      in the practice of those still on fee-for-service, it cannot be ascribed to the
      AFP. With respect to hip arthroplasty, the case was prolonged (P = 0.001) if the
      surgeon was paid via the AFP. CONCLUSION: Payment of physicians by non-fee-for
      service techniques did not have a constructive influence on measures of
      anaesthetic practice. The goal of alternate payment arrangements, to liberate
      time for academic pursuits, could not be achieved in this experimental model.

PMID- 9161746
TI  - Combined spinal and epidural anaesthesia for major abdominal surgery in infants.
AB  - PURPOSE: Subarachnoid anaesthesia is becoming increasingly popular in neonates
      and infants. However, single dose spinal anaesthesia is of limited value for
      major abdominal surgery in infants due to its short duration of action and
      inability to provide analgesia in the post operative period. A new technique of
      combined spinal and epidural anaesthesia for major abdominal surgery in the
      infant is described. METHODS: Data were gathered prospectively from 19 infants
      presenting for upper and lower abdominal surgery. Anaesthesia was induced with a
      subarachnoid injection of tetracaine. After the subarachnoid block was
      established, an epidural catheter was placed for further intraoperative and
      postoperative management. Data collected included age and weight of the patients,
      type and duration of the surgical procedure. Doses of local anaesthetics as well
      as the need for intraoperative and postoperative supplements were recorded. An
      illustrative case report is provided. RESULTS: Infants studied represented a wide
      range of weights (1520-7840 g). Spinal anaesthesia was successful in all 19
      patients. A variety of extensive surgical procedures including small bowel
      resections and various genitourinary procedures were successfully performed. In
      17 patients a functioning epidural catheter was in place postoperatively. In
      these patients effective analgesia was maintained with dilute solutions of
      epidural bupivacaine. Only three doses of narcotic were required for pain
      control. No patient required postoperative mechanical ventilation or tracheal
      intubation. CONCLUSION: Combined spinal and epidural anaesthesia is a potential
      option to general anaesthesia for major abdominal surgery in infants.

PMID- 9161747
TI  - Concurrent subarachnoid haemorrhage and myocardial injury.
AB  - PURPOSE: Subarachnoid haemorrhage is frequently associated with myocardial injury
      and dysfunction. This report describes such a case, reviews the understanding of
      this phenomenon, and discusses the implications for timing of surgical clipping
      of intracranial aneurysm in patients with concurrent myocardial damage. CLINICAL
      FEATURES: A 64-yr-old women presented with syncope and congestive heart failure.
      A diagnosis of subarachnoid haemorrhage was made three days following the initial
      diagnosis of myocardial infarction. The patient presented for clipping of an
      intracranial aneurysm on day 36, after her cardiac status had stabilized. No new
      myocardial ischaemic events occurred, either intra-operatively or post
      operatively. Ultimate neurological recovery was poor. CONCLUSIONS: This case
      report demonstrates four important aspects of the clinical course of patients
      with concurrent subarachnoid haemorrhage and myocardial damage: 1) On
      presentation, cardiac features may predominate, and delay diagnosis and treatment
      of the underlying subarachnoid haemorrhage. 2) Left ventricular dysfunction,
      although dramatic, is usually transient. 3) There is confusion regarding the
      appropriate cardiac risk assessment and management in such patients when
      presenting for surgery. 4) Long-term morbidity is most often related to
      neurological, not medical, complications.

PMID- 9161748
TI  - Protamine-induced hypotension and bradycardia in a cardiac transplant patient.
AB  - PURPOSE: The potential for functional reinnervation of the transplanted heart in
      man is controversial. We report the sudden onset of bradycardia in a cardiac
      transplant patient following a period of hypotension subsequent to the
      administration of protamine. Possible mechanisms underlying this response,
      including reinnervation of the transplanted heart, are assessed. CLINICAL
      FEATURES: Eight weeks after cardiac transplantation, a patient returned to
      hospital for a left femoral-tibial artery bypass vein graft. The patient was
      anaesthetized using general anaesthesia. Upon completion of the procedure,
      protamine was administered to reverse the heparin-induced anticoagulation.
      Although administration of a 5.0 mg "test-dose" appeared to be without
      cardiovascular effect, after an additional 20.0 mg, blood pressure decreased from
      98/52 to 62/40 mmHg. After blood pressure reached its nadir, heart rate decreased
      precipitously from 57 to 29 beats.min-1. CONCLUSIONS: This report demonstrates
      that heart rate can change considerably in patients who have undergone cardiac
      transplantation. It is argued that the change in heart rate observed in the
      present report cannot be explained by reinnervation of the transplanted heart, as
      the patient had undergone transplantation only eight weeks previously. Rather, we
      suggest that the change was mediated by mechanisms intrinsic to the transplanted
      heart and extrinsic to the CNS.

PMID- 9161750
TI  - Stethoscopy during anaesthesia.
AB  - PURPOSE: First, to determine when, following the description of stethoscopy by
      Laennec, it was used by anaesthetists in an operating room and, second, to
      describe the developing possibilities for stethoscopic monitoring. METHODS: A
      manual search of the medical literature based on Index Medicus and relevant
      publications were obtained and analyzed. Textbooks randomly available were also
      read. PRINCIPAL FINDINGS: Stethoscopy was first described early in the 20th
      century but was not widely recommended for anaesthesia until the 1950s. The
      change in attitude to stethoscopy during anaesthesia was probably due to
      alterations in anaesthesia delivery; increasing difficulty in employing direct
      human sensing. However the complexity of practice often makes traditional
      stethoscopy ergonomically unsatisfactory. Substantial research in the sensing and
      analysis of lung sounds support the contention that cheap visual displays of
      information from suitably designed sensors could be made available for
      anaesthetists. CONCLUSION: Current advances in sensing, analysis, and display of
      lung sounds could be used to create a simple and cheap device helpful for
      monitoring in the operating room.

PMID- 9161749
TI  - Natural inhibitors of cholinesterases: implications for adverse drug reactions.
AB  - PURPOSE: Acetylcholinesterase and butyrylcholinesterase are two closely related
      enzymes important in the metabolism of acetylcholine and anaesthetic drugs,
      including succinylcholine, mivacurium, and cocaine. The solanaceous
      glycoalkaloids (SGAs) are naturally occurring steroids in potatoes and related
      plants that inhibit both acetylcholinesterase and butyrylcholinesterase. There
      are many clinical examples of direct SGA toxicity due to cholinesterase
      inhibition. The aim of this study was to review the hypotheses that (1) SGAs may
      be the evolutionary driving force for atypical butyrylcholinesterase alleles and
      that (2) SGAs may adversely influence the actions of anaesthetic drugs that are
      metabolized by acetylcholinesterase and butyrylcholinesterase. SOURCE: The
      information was obtained by Medline search and consultation with experts in the
      study of SGAs and cholinesterases. PRINCIPAL FINDINGS: The SGAs inhibit both
      acetylcholinesterase and butyrylcholinesterase in numerous in vitro and in vivo
      experiments. Although accurate assays of SGA levels are difficult, published data
      indicate human serum SGA concentrations at least ten-fold lower than required to
      inhibit acetylcholinesterase and butyrylcholinesterase in vitro. However, we
      review evidence that suggests the dietary ingestion of SGAs can initiate a
      cholinergic syndrome in humans. This syndrome appears to occur at SGA levels
      lower than those which interfere with anaesthetic drug catabolism. The world
      distribution of solanaceous plants parallels the distribution of atypical alleles
      of butyrylcholinesterase and may explain the genetic diversity of the
      butyrylcholinesterase gene. CONCLUSION: Correlative evidence suggests that
      dietary SGAs may be the driving force for atypical butyrylcholinesterase alleles.
      In addition, SGAs may influence the metabolism of anaesthetic drugs and this
      hypothesis warrants experimental investigation.

PMID- 9161751
TI  - Intrathecal neurokinin-1 receptor antagonist reduces isoflurane MAC in rats.
AB  - PURPOSE: To study the effects of intrathecal administration of a neurokinin-I(NK
      I) receptor antagonist (CP96,345) on the minimum alveolar anaesthetic
      concentration (MAC) of isoflurane in anaesthetized rats, and on the locomotive
      activity of conscious rats. METHODS: Wistar rats (n = 36) were fitted with
      indwelling intrathecal catheters, and the MAC of isoflurane was determined
      following the intrathecal administration of saline (control group) or the NK-I
      receptor antagonist CP96,345 (CP) at 1, 10 and 100 micrograms. Subsequently a
      reversal dose of intrathecal Substance P (SP) at 1, 10 and 100 micrograms was
      administered and MAC isoflurane was redetermined. Conscious rats (n = 35) were
      also examined for the presence of locomotor dysfunction following intrathecal
      administration of CP and SP. Animals were randomly assigned to each treatment
      group and the investigators were blinded. RESULTS: CP at 10 and 100 micrograms
      reduced MAC isoflurane by 9.9% and 15.3%, respectively (P < 0.05). Intrathecal
      administration of SP reversed the decreases in MAC by CP; however, locomotive
      activity was not changed. CONCLUSION: These results suggest that the NK-1
      receptor plays an important role in determining the MAC of isoflurane by
      inhibition of pain transmission in the spinal cord.

PMID- 9161752
TI  - Do enflurane and isoflurane interfere with the release, action, or stability of
      endothelium-derived relaxing factors?
AB  - PURPOSE: The volatile anaesthetics enflurane and isoflurane inhibit the
      endothelium dependent-relaxation in some in vitro preparations. To determine
      their site of action on the endothelium-derived relaxing factor/nitric oxide
      (EDRF/NO) pathway, experiments were conducted in a bioassay system. METHOD:
      Continuously perfused cultured bovine aortic endothelial cells (BAEC) were the
      source of EDRF/NO while a phenylephrine-precontracted denuded rabbit aortic ring,
      directly superfused by the BAEC effluent served to detect EDRF/NO. The effect of
      basal and bradykinin (Bk)-stimulated EDRF/NO release on vascular tension was
      measured. The effect of 4% enflurane or 2% isoflurane on EDRF/NO-induced
      relaxation was determined. RESULTS: Enflurane added to the perfusate either
      upstream or downstream in relation to BAEC attenuated the relaxation induced by
      Bk at low concentrations. On the other hand, isoflurane, added either upstream or
      down-stream to BAEC, potentiated the relaxation induced by the basal release of
      EDRF but attenuated the relaxation induced by the Bk stimulated release of EDRF.
      Neither enflurane nor isoflurane attenuated the relaxation induced by sodium
      nitroprusside (SNP), an NO donor. CONCLUSION: Enflurane decreases the stability
      of EDRF/NO released after Bk stimulation while isoflurane can have opposite
      effects depending on whether the relaxation results from basal or Bk-stimulated
      release of endothelial derived relaxing factor(s). Isoflurane increases the
      stability or action of the basal relaxing factor, decreases the stability of the
      Bk-stimulated relaxing factor (which is probably NO).

PMID- 9161753
TI  - Anaesthesia in Barbados.
AB  - PURPOSE: To describe the anaesthesia services in Barbados: to present the major
      challenges confronting the Anaesthesia Department of the government-owned Queen
      Elizabeth Hospital (QEH): and to describe the Department's approaches to optimise
      safety and cost-effectiveness of anaesthesia at QEH. SOURCE OF INFORMATION:
      Authors (KBS, HSLM, RAH), who collectively provided more than 50 yr of
      anaesthesia at QEH; the Dean (ERW) of the University of West Indies Medical
      School (Barbados campus); archives of Barbados; and records of QEH. PRINCIPAL
      FINDINGS: The government of Barbados provides modern health care services to all
      of its citizens, primarily at QEH. Barbados, however, has tight financial
      constraints, infrastructural limitations, and a bureaucratic administration that
      predispose QEH's Anaesthesia Department to unexpected depletions of drugs and
      disposable supplies, sporadic shortages of personnel and functioning equipment,
      and occasional quality assurance problems. To deal with such problems, the
      Anaesthesia Department has implemented several pro-active measures: establishing
      an audit system to prevent depletion of imported drugs and supplies: training
      local personnel to maintain equipment: purchasing an oxygen concentrator to
      reduce oxygen costs: decreasing nitrous oxide use (expensive in Barbados): and
      initiating its own quality and safety standards. CONCLUSION: Continuous delivery
      of high quality, cost-effective anaesthesia care requires thoughtful planning by
      administrators and judicious resource allocations. Health care administrators and
      clinical departments need to work together closely to establish a framework that
      enables departments to play a major role in determining how the institution's
      limited financial resources are best allocated to meet the departmental
      priorities.

PMID- 9161754
TI  - Thiopentone or propofol for LMA insertion?

PMID- 9161756
TI  - Neuromuscular monitoring in paediatric intensive care patients.

PMID- 9161755
TI  - Double burst stimulation2,3 at submaximal current.

PMID- 9161757
TI  - Feeding: an alternative to sedation in children.

PMID- 9161758
TI  - Delayed bilateral spinal anaesthesia.

PMID- 9161759
TI  - Two oxygen delivery devices compared in a modified laryngeal mask airway.

PMID- 9161760
TI  - The age of misery: affective disorders on the rise.

PMID- 9161762
TI  - Bipolar disorder: from families to genes.
AB  - BACKGROUND: Genetic factors are known to contribute to the etiology of bipolar
      illness, but the actual genetic mechanisms remain to be clarified. METHODS: This
      paper reviews the research undertaken to establish the genetic basis of bipolar
      illness and to elucidate the nature of its genetic predisposition. RESULTS: The
      presented findings suggest that bipolar affective disorder is a heterogeneous
      condition characterized by a complex relationship between the genetic
      susceptibility and the clinical presentation. Linkage studies have generated
      promising and replicated findings on chromosomes 18 and 21. CONCLUSION: In spite
      of the methodological difficulties inherent in the genetic study of psychiatric
      disorders recent investigations have made important advances and promise to
      identify specific susceptibility genes.

PMID- 9161761
TI  - Epidemiology of affective disorders: a review.
AB  - OBJECTIVE: To review the epidemiology of affective disorders. METHODS: This paper
      reviews recent studies, many of which have used standardized methodology and
      classification systems, and summarizes their major findings. It also presents
      trends with particular reference to major depression. RESULTS: There have been
      major advances in the last 15 years, with many investigators using standard
      methods in different countries, cultures, and races. Rates of major depression
      are probably increasing, and both major depression and bipolar disorder are
      occurring at younger ages. CONCLUSIONS: Affective disorders present a major
      public health problem with poor recognition, diagnosis, and treatment. There is
      little coordinated action to reduce untreated morbidity despite the availability
      of reasonably safe, effective, and economical treatments and the established
      effectiveness of continuing education programs for providers.

PMID- 9161763
TI  - Speaking graphically: an introduction to some newer graphing techniques.
AB  - The vast majority of graphs appearing in the psychiatric literature consist of
      the traditional line graphs, histograms, and bar charts. Over the past decade,
      new graphing techniques have appeared which make the data easier to read and
      which present much more information than simply group means and confidence
      intervals. These methods include horizontal bar charts, dot charts, stem-and-leaf
      plots, box plots, and notched box plots. This paper describes these new
      techniques, as well as older ones, such as smoothing, and warns against using
      some of the options found in graphics programs: 3-dimensional (3-D) graphs,
      stacked graphs, and pie charts.

PMID- 9161764
TI  - A cross-sectional study of private psychiatric practices under a single-payer
      health care system.
AB  - OBJECTIVES: To examine current concerns that in the Canadian single-payer mental
      health care system, the "rich worried well" (that is, wealthy individuals who are
      worried yet mentally well) may overuse psychiatric services, while low-income,
      uninsured mentally ill individuals may remain undertreated. The current study
      focuses on the mental health care in the Canadian region of Ottawa-Carleton,
      where a single-payer system provides universal access to mental health services,
      to assess how psychiatric services are provided by psychiatrists in private
      practice. METHOD: One hundred and seven private psychiatrists working in the
      region of Ottawa-Carleton completed a questionnaire which contained questions
      about the sociodemographic characteristics and background of the psychiatrists
      themselves and which asked the psychiatrists specific questions about the
      sociodemographic status, diagnosis, and treatment of each patient seen on
      November 10, 1994. RESULTS: Approximately 93% of the patients seen met criteria
      for one or more Axis I disorders, of which mood and anxiety disorders were the
      most common. Wealthier patients were relatively underrepresented among the
      patients treated by the private psychiatrists. In addition, we found no
      significant differences in the distribution of Axis I, Axis II, and Axis III
      disorders between patients earning below $30,000 per year compared with patients
      earning above $60,000 per year. CONCLUSIONS: Our results suggest that outpatient
      psychiatric care delivered by private psychiatrists in a Canadian single-payer
      system targets primarily individuals with major psychiatric disorders and does
      not seem to favour "the worried well." Larger epidemiological studies with
      independent assessments of psychiatric populations are necessary to confirm our
      findings.

PMID- 9161765
TI  - Emotional distress and substance abuse as risk factors for suicide attempts.
AB  - BACKGROUND: Both depression and hopelessness have been found to be closely
      related to suicide risk among adolescents and adults. Substance abuse has also
      been found to play a role in the suicide process with adults, but it is still
      unclear how much substance abuse influences suicide in adolescents. METHOD: The
      present study examined the relationship between substance abuse, emotional
      distress, and suicidal intent among 115 adolescent psychiatric inpatients who had
      attempted suicide. RESULTS: Measures of emotional distress, as well as the
      measures of substance abuse, were significantly intercorrelated. Correlations
      across domains (emotional distress versus substance abuse), however, varied by
      gender. Among adolescent females, both depression and hopelessness were
      significantly related to suicidal intent, whereas among adolescent males, only
      depression was related to suicidal intent. Also, alcohol abuse was significantly
      related to depression and hopelessness in adolescent males. CONCLUSIONS:
      Hopelessness may not be as useful an indicator of suicide risk among adolescent
      males as it is with adolescent females. Intervention and prevention programs
      designed for adolescent females should identify and address feelings of
      depression and hopelessness. New intervention and prevention programs may need to
      be developed for adolescent males.

PMID- 9161766
TI  - Is Mr Pac Man eating our children? A review of the effect of video games on
      children.
AB  - OBJECTIVE: To provide mental health professionals with an up-to-date review of
      the literature regarding the effects of playing video games on the well-being of
      children. METHOD: A computerized literature search of MEDLINE and PSYCHINFO of
      all articles written in English from 1966 to 1996 was performed. The various
      studies are organized into different sections. RESULTS: Playing video games is
      associated with a variety of physical effects including increased metabolic and
      heart rate, seizures, and tendinitis. Aggressive behaviour may result from
      playing video games, especially among younger children. There is no direct
      relationship between psychopathology or academic performance and playing video
      games. CONCLUSIONS: Video games have some adverse effects, but they are also
      valuable learning tools. Research about the role of video games is inadequate.
      The data are also limited by the lack of long-term studies and inconsistent
      findings.

PMID- 9161767
TI  - The relationship of endogenous cortisol to psychiatric disorder: a review.
AB  - OBJECTIVES: To focus on hypothalamic-pituitary-adrenal (HPA) axis activity,
      especially endogenous hypercortisolemia, to study its role in the maintenance of
      psychiatric illness, and to entertain the probability that the elderly are
      vulnerable. METHOD: Case presentation, clinical and research literature review,
      and theoretical discussion. RESULTS: Clinical and research evidence
      overwhelmingly suggest that hypercortisolemia is toxic to the hippocampus. Some
      research supports the position that it can be a treatable perpetuating factor in
      a subset of affective disorders and psychoses. Pharmacological treatments to
      correct hypercortisolemia have been used by endocrinologists. Hypercortisolemic
      treatment-resistant and nontreatment-resistant psychoses and affective disorders
      have been successfully treated by a small number of researchers who remain
      interested in this subject. Data pertaining to geriatric psychoses may be germane
      but are sparse. CONCLUSIONS: It behooves us to research diagnostic methods
      pertaining to psychoses and affective disorders associated with hypercortisolemic
      states. Very little research is available, but we must be alert to the
      possibility that the elderly are more susceptible to cortisol endotoxicosis than
      the younger adult population. Without accurate diagnosis, we cannot take
      advantage of existing antiglucocorticoid strategies.

PMID- 9161768
TI  - Published research and departments of psychiatry.

PMID- 9161769
TI  - Re: Rapid stabilization at home.

PMID- 9161770
TI  - A time to bury the tricyclic antidepressants or to praise them?

PMID- 9161771
TI  - Dysarthria: lonely symptom of tardive dystonia.

PMID- 9161772
TI  - Toxic delirium with low-dose clozapine.

PMID- 9161773
TI  - Switching between clozapine and risperidone treatment.

PMID- 9161774
TI  - Risperidone and neuropsychological test performance in cocaine-withdrawn
      patients.

PMID- 9161775
TI  - Clinical trials of antitumor agents: experimental design and timeline
      considerations.

PMID- 9161776
TI  - Neoadjuvant therapy of esophageal cancer.

PMID- 9161777
TI  - A new human herpesvirus as a factor in the pathogenesis of Kaposi's sarcoma and
      body-cavity lymphoma.

PMID- 9161778
TI  - Of snails and holy grails...

PMID- 9161779
TI  - Intensive chemoradiation followed by esophagectomy for squamous cell and
      adenocarcinoma of the esophagus.
AB  - PURPOSE: To determine the pathologic complete response rate, toxicity, and
      survival of patients with resectable squamous cell or adenocarcinoma of the
      esophagus treated with a 30-day preoperative chemoradiation regimen and surgical
      resection. PATIENTS AND METHODS: Fifty patients (16 squamous, 33 adeno, one
      undifferentiated) who had carcinoma of the esophagus (limited to the primary
      tumor and regional or celiac nodes) were treated with cisplatin 26 mg/m2/day
      continuous infusion days 1 through 5 and 26 through 30, 5-fluorouracil (5-FU) 300
      mg/m2/day continuous infusion days 1 through 30, and radiation 44 Gy, 2 Gy/fx in
      22 daily fractions, days 1 through 30, followed by esophagectomy. RESULTS: Forty
      seven patients underwent esophagectomy (94% operability rate), and 45 had total
      gross removal of disease and negative margins of resection (90% resectability
      rate). Nineteen patients (40%) had a pathologic complete response (CR). Forty
      (80%) received 100% of the planned cisplatin dose, 29 (58%) received 100% of the
      planned 5-FU dose, and 40 (80%) received > or = 80% of the planned 5-FU dose.
      Forty-five (90%) received the planned 44-Gy radiation dose. Grade 3 or 4
      neutropenia occurred in 60% of patients. The incidence of febrile neutropenia was
      34%. There was one septic death during chemoradiation and no operative deaths.
      Weight loss requiring nutritional support occurred in 50% of patients, secondary
      to anorexia, dysphagia, and/or esophagitis. The survival of all registered
      patients at a median follow-up of 43 months was 2-year survival 58%, median 31.3
      months. Survival analysis by histology showed no difference between the two
      histologic types (squamous vs adenocarcinoma). However, survival by pathologic
      response was significantly different: pathologic CR, 19 patients, 2-year survival
      78%, median survival 58 months; and pathology positive, 28 patients, 2-year
      survival 46%, median survival 22.4 months. A Cox proportional hazards model and
      logistic regression analysis demonstrated a significant survival advantage for
      pathologic CRs and stage I disease versus higher-stage disease and a correlation
      between chemotherapy dose received and pathologic staging. DISCUSSION: This 30
      day chemoradiation regimen followed by surgery resulted in a high pathologic
      complete response rate, 40%, and apparent survival advantage for this group. The
      median survival rate of 31.3 months and 2-year survival rate of 58% suggest that
      this regimen may improve survival over surgical treatment alone. Randomized
      trials with large accrual and statistical power are necessary to confirm our
      results and to determine optimal treatment.

PMID- 9161780
TI  - Kaposi's-sarcoma-associated herpesvirus is detected in peripheral blood
      mononuclear cells of HIV-infected homosexuals more often than in heterosexuals.
AB  - PURPOSE: The Kaposi's-sarcoma-associated herpesvirus is thought likely to play an
      important part in the pathogenesis of Kaposi's sarcoma, which is the most common
      tumor in AIDS patients. To determine whether peripheral blood is also infected by
      the virus, we prospectively tested mononuclear cells from HIV-infected
      individuals, both with and without Kaposi's sarcoma. PATIENTS AND METHODS: Thirty
      three patients with AIDS were studied. Twenty-three were homosexuals, and 10 of
      these patients had Kaposi's sarcoma. All 10 nonhomosexual patients were free of
      Kaposi's sarcoma. PCR amplification of peripheral blood mononuclear cells was
      performed for a 233-base-pair segment of Kaposi's-sarcoma-associated herpesvirus
      on all patients. Fisher's exact test was used to compare the patient groups.
      RESULTS: Kaposi's-sarcoma-associated herpesvirus sequences were detected in the
      peripheral blood mononuclear cells of homosexual men both with (7/10) and without
      (5/13) Kaposi's sarcoma. However, none of the nonhomosexual patients (0/10) had
      detectable virus. Therefore, those with Kaposi's sarcoma are at greater risk for
      Kaposi's-sarcoma-associated herpesvirus infection than patients without Kaposi's
      sarcoma, and among HIV-positive patients without Kaposi's sarcoma, homosexuals
      are more likely to have detectable Kaposi's-sarcoma-associated herpesvirus than
      are nonhomosexuals. In the homosexual patients, the presence of virus was
      unrelated to total CD4+ cell counts. A comparative dilutional analysis showed
      that the nonhomosexual patients had a low viral load in their peripheral blood
      mononuclear cells relative to most homosexuals with Kaposi's sarcoma. Sequential
      studies on two patients revealed clearing of the virus while on therapy; one
      patient was treated for HIV with the protease inhibitor indinavir, and the other
      patient was treated for Kaposi's sarcoma with liposomal doxorubicin. CONCLUSIONS:
      These results indicate that Kaposi's-sarcoma-associated herpesvirus is harbored
      in peripheral blood mononuclear cells of HIV-infected patients, and that the
      rates of infection are significantly higher in homosexual men compared with their
      nonhomosexual counterparts. The significance of viral clearing in response to
      therapy is unknown but warrants further study, as prophylactic treatment for this
      virus might alter the occurrence of Kaposi's sarcoma in this susceptible patient
      population.

PMID- 9161781
TI  - Outpatient subcutaneous interleukin-2 and interferon-alpha for metastatic renal
      cell cancer: five-year follow-up of the Cytokine Working Group Study.
AB  - PURPOSE: A phase II trial of outpatient subcutaneous (SC) interleukin-2 (rIL-2)
      plus interferon-alpha (IFN-alpha 2B) was performed in patients with metastatic
      renal cell cancer. A 5-year follow-up of that Cytokine Working Group study is
      presented. PATIENTS AND METHODS: Forty-seven patients meeting eligibility
      criteria of previous Cytokine Working Group studies were treated on an outpatient
      basis with SC rIL-2 (Chiron, Emeryville, CA), 5 x 10(6) IU/m2/dose q 8 hr x 3,
      then daily, 5 days per week, and IFN-alpha 2B (Schering-Plough, Kenilworth, NJ),
      5 x 10(6) IU/m2/dose three times weekly for 4 weeks. After a 2- to 4-week break,
      patients were scheduled to continue treatment for up to six cycles. RESULTS:
      There were two complete and six partial responders (17% response rate, 95% CI: 8%
      31%). Median duration of response was 12 months (range 1-49+ months), with
      complete responses of 15 and 49+ months. Responding sites of disease included
      lung, nodes, soft tissue, bone, and liver. Dose and schedule were adjusted to
      control toxicity at grade 2/3 levels, with 50% requiring dosage alterations.
      Grade 2/3 toxicity included fatigue, nausea/vomiting, diarrhea, anorexia, fluid
      overload, rash, CNS, injection site pain, chest pain/palpitations (including
      atrial fibrillation requiring treatment, two patients), and hypotension. Grade 4
      toxicity included dehydration (seven patients), vomiting (one patient), and
      irreversible renal failure with crescentic glomerulonephritis requiring dialysis
      (one patient). CONCLUSION: SC rIL-2 plus IFN-a2B is tolerated in the outpatient
      setting with frequent dose adjustments. The overall response rate of this regimen
      is similar to that seen with high-dose rIL-2 alone; however, the response
      duration appears to be shorter.

PMID- 9161782
TI  - The interaction of hydroxyurea and ionizing radiation in human cervical carcinoma
      cells.
AB  - PURPOSE: The results from prior in vitro and in vivo studies and recent phase 3
      clinical trials suggest a significant potential role for hydroxyurea (HU) as a
      clinical radiosensitizer for cervix cancer. However, a detailed study of possible
      cellular mechanisms of radiosensitization in human cervix cancer cells as a
      consequence of dose and timing of HU and ionizing radiation (IR) has not been
      performed. This in vitro study analyses the interactions of HU and IR in a human
      cervical carcinoma cell line, Caski. MATERIALS AND METHODS: Exponentially growing
      Caski cells were continuously exposed to clinically achievable but minimally
      cytotoxic concentrations of HU (0.3-3.0 mM) for various time intervals (6, 12,
      18, 24, and 30 hours) up to one population doubling time either prior to or
      immediately following IR (2-8 Gy). The radiation survival data were analyzed
      using our modification of the linear-quadratic model to test for an interaction
      (greater than additive). The effects of HU alone, IR alone, and the combination
      on cell cycle progression and on apoptotic cell death in exponentially growing
      Caski cells were measured. RESULTS: We report a significant HU-IR interaction
      (radiosensitization) based on the sequence of HU exposure (post- > pre-IR) and
      with increasing concentrations of HU (0.3-3.0 mM), but no effect on
      radiosensitization with the duration of exposure to HU for up to one cell
      population doubling (6-30 hours). HU concentration has a significant effect on
      both alpha and beta linear-quadratic values in the post-IR sequences. Exposures
      of exponentially growing Caski cells to 1 mM and 3 mM HU alone result in a
      complete block in early S phase throughout the 30-hour exposure, while 0.3 mM HU
      causes a transient early S-phase block over the initial 12 to 18 hours of
      exposure. HU alone has no effect on cell cycle progression in G1 or G2/M
      populations but results in a large apoptotic population (31% following 1 mM HU x
      30 hours), which appears to be the principal mechanism of drug cytotoxicity in
      these cells. IR alone (4 or 6 Gy) results in a significant G2 delay for 6 to 18
      hours following IR but no G1 delay and a small apoptotic population at 30 hours
      post-IR (5.4% vs 2.1% in non-IR controls). The use of HU (0.3 or 1.0 mM)
      following IR (4 or 6 Gy) results in a significantly larger G2 delay compared with
      IR alone, but with only an additive effect on the apoptotic population.
      CONCLUSIONS: These in vitro data demonstrate that radiosensitization of Caski
      cells is more significant with post-IR exposures to clinically achievable
      concentrations of HU. This HU-IR interaction is associated with an increased G2
      delay, suggesting a reduction in IR damage repair. However, this interaction
      appears to be independent of the cytotoxicity (principally by apoptosis) from HU
      alone.

PMID- 9161783
TI  - Continuous hyperthermic peritoneal perfusion with cisplatin for the treatment of
      peritoneal mesothelioma.
AB  - PURPOSE: Peritoneal mesothelioma remains a difficult therapeutic challenge.
      Aggressive debulking combined with continuous hyperthermic peritoneal perfusion
      (CHPP) using cisplatin (CDDP) is a novel strategy for the treatment of peritoneal
      mesothelioma, allowing high regional delivery of chemotherapeutics and
      hyperthermia while minimizing systemic toxicity. PATIENTS AND METHODS: From June
      1993 to May 1996, 10 patients with peritoneal mesothelioma (six men, four women;
      mean age 40 years, range 15-57) underwent tumor debulking followed by a 90-minute
      CHPP. CHPP parameters included mean initial CDDP of 120 micrograms/mL (range 81
      166), perfusate volume 5.2 L (range 4-7), flow 1.5 L/min, intraperitoneal
      temperature at three locations-41.5 degrees C, 40.5 degrees C, 41.1 degrees C,
      and core temperature 38.4 degrees C (range 37.2 degrees C-39.5 degrees C). Nine
      of 10 patients had malignant peritoneal mesothelioma, eight with associated
      ascites, while the tenth had a symptomatic, multiply recurrent benign peritoneal
      mesothelioma. Nine of 10 patients were optimally debulked. Pharmacokinetics were
      performed on blood and perfusate samples on nine patients; CDDP levels were
      quantitated by atomic absorption spectroscopy. RESULTS: Total perfusate cisplatin
      AUC was a mean of 21-fold higher (range 2- to 116-fold) than total serum
      cisplatin AUC, and serum CDDP behaved similarly to systemically administered
      CDDP. Median follow-up after CHPP is 10 months (range 2-32), with no treatment
      related mortality. In eight optimally debulked patients there is no evidence of
      recurrent disease clinically or by CT or MRI. Seven patients with symptomatic
      ascites have been completely palliated. CONCLUSIONS: CHPP with CDDP is well
      tolerated with no significant regional toxicity. Because favorable CDDP
      pharmacokinetics suggest the potential for enhanced CDDP tumoricidal effect
      during CHPP, tumor debulking and CHPP may represent an effective strategy for the
      treatment of peritoneal mesothelioma.

PMID- 9161784
TI  - Improved control of high-dose-cisplatin-induced acute emesis with the addition of
      prochlorperazine to granisetron/dexamethasone.
AB  - PURPOSE: To evaluate the antiemetic efficacy and safety of adding the dopamine
      antagonist prochlorperazine to the combination of granisetron and dexamethasone
      in the prevention of acute nausea and vomiting following high-dose cisplatin.
      PATIENTS AND METHODS: Sixty patients receiving cisplatin (> or = 75 mg/m2)
      (median dose = 100 mg/m2) were enrolled at three sites. Patients received
      prochlorperazine spansule 15 mg orally, 60 minutes prior to and 12 hours after
      cisplatin; dexamethasone 20 mg intravenously, 45 minutes prior to cisplatin, and
      10 mg intravenously or orally, 12 hours after cisplatin; and granisetron 10
      micrograms/kg intravenously, 30 minutes prior to cisplatin. Efficacy was assessed
      during the 24-hour period after cisplatin using complete antiemetic response (no
      emetic episodes and no rescue antiemetics) and patient assessment of nausea and
      satisfaction using 100-mm visual analog scales (nausea: 0 = none, 100 = nausea as
      bad as it can be; satisfaction: 0 = not at all satisfied, 100 = satisfied as can
      be). RESULTS: Complete response (0 emetic episodes) was noted in 84% (49/58) of
      patients. Forty-two patients (72%) experienced no nausea. The mean change in
      posttreatment nausea visual analog scales from baseline was 8.9 mm. Forty-eight
      patients (83%) were completely satisfied with their antiemetic treatment. The
      mean posttreatment patient satisfaction score was 92 mm. Treatment was well
      tolerated, with infrequent and minor adverse events. CONCLUSIONS: This three-drug
      antiemetic regimen is well tolerated and highly effective in the prevention of
      acute nausea and vomiting arising from high-dose cisplatin. Further studies
      evaluating this regimen are warranted.

PMID- 9161785
TI  - Microvessel density and outcome of adjuvant treatment of breast cancer patients.

PMID- 9161786
TI  - Transplantation.

PMID- 9161787
TI  - Bone marrow transplantation for low-grade B-cell malignancies.
AB  - Autologous and allogeneic bone marrow transplantation are widely used for
      treatment of a number of hematologic malignancies, including aggressive non
      Hodgkin's lymphomas. However, relatively small numbers of patients with low grade
      lymphoma or chronic lymphocytic leukemia have been treated using this approach.
      There is reluctance to perform potentially lethal treatment procedures for
      diseases with relatively long natural histories that tend to occur in more
      elderly patients. Although these diseases are characterized by initial
      chemotherapy responsiveness, many of these patients are heavily pretreated and
      have acquired chemotherapy resistance and decreased marrow reserve by the time of
      consideration of bone marrow transplantation as a treatment option. The very high
      incidence of bone marrow infiltration in these diseases has made it difficult to
      use autologous stem cells for rescue after high dose myeloablative therapy.
      However, because these diseases are incurable using conventional therapy, there
      has been increased interest recently in the use of high dose ablative therapy and
      stem cell support. Studies have focused on the timing of such procedures (either
      early in the treatment course before chemoresistance develops or after subsequent
      relapse), the source of stem cells, and whether purging of malignant cells from
      autologous stem cells is required.

PMID- 9161788
TI  - High-dose chemotherapy for the treatment of breast and ovarian cancer.
AB  - Breast cancer is currently the primary indication for high-dose chemotherapy with
      autologous hematopoietic progenitor cell support. Recent advances include the
      first randomized trial comparing high-dose chemotherapy with conventional-dose
      chemotherapy in patients with metastatic disease, new and improved methods for
      detection of tumor cells in the autologous graft, new high-dose chemotherapy
      regimens, new trials exploring multicycle high-dose chemotherapy, and the
      development of prognostic factors that may predict the outcome of patients who
      receive this treatment. In patients with ovarian cancer, a recently activated
      intergroup randomized study of high-dose chemotherapy compared with conventional
      dose chemotherapy should help clarify the role of high-dose chemotherapy for the
      treatment of this disease.

PMID- 9161789
TI  - Bone marrow transplantation for inherited diseases.
AB  - Allogeneic bone marrow transplantation has been used successfully for the
      treatment of a variety of inherited diseases. The goal of transplantation in this
      setting is to provide a sufficient degree of sustained marrow engraftment to
      allow longterm amelioration of the inherited disease phenotype. Many factors
      influence the likelihood of achieving this goal, including donor availability,
      conditioning regimen, marrow processing, and the nature and extent of progression
      of the disease. For many inherited diseases early diagnosis is imperative because
      the outcome of transplantation is more favorable when performed prior to the
      development of significant organ damage from the disease, its complications, or
      treatment. Although the results of bone marrow transplantation are good for some
      inherited diseases and are improving for others, significant problems remain such
      as donor availability, conditioning regimen toxicity, graft failure, and graft
      versus-host disease. This review describes some of the unique features of bone
      marrow transplantation for inherited diseases and discusses recent advances in
      this area.

PMID- 9161790
TI  - Graft-versus-host disease.
AB  - Graft-versus-host disease (GVHD) continues to be a major obstacle to the success
      of allogeneic bone marrow transplantation. Furthermore, several clinical
      strategies being employed at this time in the field of bone marrow
      transplantation have had an impact on GVHD. In addition to the usual division of
      topics such as pathophysiology, and acute and chronic GVHD, papers dealing with
      the impact on GVHD created by allogeneic peripheral blood cell transplantation,
      donor leukocyte infusions, and unrelated bone marrow transplantation are
      considered separately.

PMID- 9161791
TI  - Adoptive immunotherapy with donor lymphocyte transfusions.
AB  - Adoptive immunotherapy denotes the transfer of immunocompetent cells for the
      treatment of leukemia, cancer, or viral disease. It has regained much interest
      through the success of treating recurrent leukemia after allogeneic bone marrow
      transplantation with the transfusion of donor lymphocytes. Chimerism and
      transplantation tolerance toward the donor offer the possibility of adoptive
      immunotherapy using donor lymphocytes. In animal studies, donor lymphocytes could
      be transfused into the chimeric animal, if the transfusion was delayed after
      marrow transplantation. Transfused lymphocytes exhibit a graft-versus-leukemia
      effect and increase chimerism. Immunity could be transferred and immune
      reactivity toward new antigens improved. In human patients transfusion of donor
      lymphocytes was studied in leukemia recurring after marrow transplantation. It
      was very effective in the treatment of chronic myelogenous leukemia recurring
      after marrow transplantation. It was also effective in some patients with acute
      myeloid leukemia, myelodysplastic syndrome and myeloma; in acute lymphoblastic
      leukemia and lymphoma responses were rare. Responses in solid tumors as breast
      cancer have been described. Major complications are graft-versus-host disease and
      myelosuppression. Myelosuppression could be compensated by the transfusion of
      marrow. Graft-versus-host disease can be modified by the depletion of CD8
      positive T cells from the lymphocyte concentrate or by transfusing very low
      numbers of cells and increasing doses in a stepwise fashion. The role of
      concomitant treatment with cytokines and activation of T cells by dendritic cells
      and vaccination remains to be defined.

PMID- 9161792
TI  - Lung and mediastinum.

PMID- 9161793
TI  - Preoperative chemotherapy for stage IIIA non-small cell lung cancer.
AB  - Recent studies have shown that preoperative chemotherapy is feasible and
      advisable for patients with stage IIIA mediastinoscopically confirmed N2
      involvement in non-small cell lung cancer. Such studies confirm the crucial
      pillar of attaining complete resection, and the importance of downstaging N2
      disease as a useful surrogate for long-term survival. Resectability rate is about
      70% in almost all studies examined. Better means of predicting resectability and
      relapse are addressed, such as the potential role of positron emission tomography
      and some hints for the management of replication error-positive non-small cell
      lung cancer patients. A major issue for the role of preoperative chemotherapy is
      how not to confuse apples and oranges. Although the role of surgery alone or
      radiotherapy is considered suboptimal for treatment of stage IIIA N2, whether
      surgery is required remains to be clarified. Furthermore, large randomized
      studies of chemoradiation followed by surgery versus chemoradiation alone are
      needed as well as modification of the current tumor, node, metastasis
      classification in order to better select those patients for whom preoperative
      chemotherapy would be beneficial. The surgeon's judgment and skill are essential
      in the identification of eligible patients and multimodality treatment research
      is also spreading toward early disease and some subsets of T4 non-small cell lung
      cancers.

PMID- 9161794
TI  - Thymic neoplasms.
AB  - Thymomas are infrequent and relatively indolent mediastinal tumors. They are
      usually encapsulated and readily removed. Invasive tumors, even if completely
      resected, require additional therapy. Although efforts have been made to relate
      histopathologic characteristics to outcome, the most important prognostic factors
      are stage and ability to achieve complete resection. The responsiveness of these
      tumors to chemotherapy and radiation therapy has led to combining all three
      modalities in a consistent sequence to derive maximal benefit from each to
      outcome in patients with locally advanced stage tumors.

PMID- 9161795
TI  - Pulmonary complications of cancer treatment.
AB  - Great strides have been made in the treatment of cancer. This success, however,
      has not come without a price. Pulmonary complications of cancer treatment have
      proven to be common and often result in significant morbidity. The manifestations
      of such complications may range from an asymptomatic patient with an abnormal
      chest, radiograph to one with transient dyspnea to varying degrees of chronic
      pulmonary insufficiency to an acute lethal event. Each of the major treatment
      modalities, surgery, radiation therapy, and chemotherapy, carries a significant
      complication rate that often limits its effectiveness. When two or more
      modalities are used concurrently or sequentially, the risk of complications
      increases further. The respiratory system, for a number of reasons, has proven to
      be especially vulnerable to treatment-related complications.

PMID- 9161796
TI  - Malignant pericardial effusion.
AB  - The clinical symptoms of cardiac tamponade associated with malignancy are
      reviewed, and the importance of these symptoms in relationship to treatment
      decisions are discussed. The clinical findings of tamponade and the
      echocardiographic findings have been correlated. The approach to treatment of
      cardiac tamponade has been summarized. The various surgical techniques, including
      pericardial window formation, subxyphoid drainage, and thoracoscopy and video
      assisted thoracoscopy, are discussed and the relative benefits of the various
      procedures have been presented. Results of the less invasive percutaneous balloon
      pericardiostomy procedure have also been reviewed, and updates of recent small
      series have been included. Medical management of malignant pericardial effusion
      with small-bore tube drainage followed by sclerosis has been reviewed, and the
      results of recent series reporting the effectiveness of various sclerosing
      agents, including tetracycline, doxycycline, and bleomycin, have been compared.

PMID- 9161797
TI  - Melanoma and other skin neoplasms.

PMID- 9161798
TI  - Melanoma epidemiology.
AB  - New data show plateaus and even declines in rates of incidence and mortality due
      to melanoma among some age groups. Increased rates persist among older men,
      creating needs for health care planning. Early detection presents a paradox:
      screening activities, which may be more prevalent among those with higher
      socioeconomic status, may both increase incidence and decrease mortality (by
      diagnosing melanoma earlier and through the removal of precursor lesions).
      Studies of the development of nevi show that they are robust risk markers for
      melanoma and share some epidemiologic features with melanoma. Multiple primary
      melanomas develop in 5% to 10% of subjects with melanoma and may reflect genetic
      predisposition. Combined analyses and methodologic studies have refined
      estimation of the effects of risk factors.

PMID- 9161799
TI  - Surgical issues in the management of melanoma.
AB  - The mainstay of treatment of cutaneous melanoma is surgical excision. Excision of
      the primary disease, lymph node metastases, and in some instances, distant
      metastases is the only therapeutic strategy that leads to long-term disease-free
      survival with rare exceptions. Surgical treatment of melanoma can be divided into
      therapy of the primary lesion, treatment of the lymph nodes, treatment of distant
      metastases, and treatment of in-transit disease by regional administration of
      intravascular chemotherapeutics. The current recommendations for each of these
      four areas is discussed in this review.

PMID- 9161800
TI  - Adjuvant therapy for melanoma.
AB  - The search for effective adjuvant therapy for melanoma has resulted in the
      testing of a remarkably broad spectrum of therapeutic agents. Until recently,
      there was little evidence to suggest a benefit for any adjuvant therapy. The
      demonstration of activity for adjuvant high-dose interferon alfa in a cooperative
      group trial resulted in Food and Drug Administration approval and has
      dramatically changed the melanoma landscape. This article reviews all the
      randomized adjuvant trials conducted to date in melanoma, discusses pertinent
      studies still in progress or awaiting analysis, and offers recommendations for
      the adjuvant treatment of melanoma patients rendered clinically disease-free by
      surgery.

PMID- 9161802
TI  - Transplantation.

PMID- 9161803
TI  - Lung and mediastinum.

PMID- 9161801
TI  - The treatment of metastatic melanoma with chemotherapy and biologics.
AB  - Metastatic malignant melanoma remains a frustrating and almost invariably fatal
      disease. Nonetheless, both cytotoxic chemotherapy and immunotherapy agents have
      shown activity against this disease, and an occasional patient will experience
      long-term benefit from therapy. Regimens involving various combinations of
      chemotherapy, the addition of either tamoxifen or interferon alfa have shown
      promise in phase III trials, but as yet no agent has proven to be superior to
      single agent dacarbazine alone. Immunotherapy with high-dose interleukin-2, has
      produced durable complete responses in a small percentage of patients, and
      combinations of cisplatin-based chemotherapy and interleukin-2-based
      immunotherapy have produced responses in approximately 50% of patients with 10%
      durable complete responses. These encouraging results have prompted the design
      and initiation of several phase III trials comparing various combination
      biochemotherapy regimens to either chemotherapy or immunotherapy alone. Several
      new cytotoxic and biologic agents including specific vaccines have recently been
      investigated, which may add to the therapeutic armamentarium. This article
      reviews the promising new developments in the treatment of metastatic melanoma,
      and it places them within in the context of established treatment approaches for
      this disease.

PMID- 9161804
TI  - Melanoma and other skin neoplasms.

PMID- 9161805
TI  - Interactions between genetic and environmental factors in colorectal
      carcinogenesis.

PMID- 9161806
TI  - Dual role of oestrogens as hormones and pro-carcinogens: tumour initiation by
      metabolic activation of oestrogens.
AB  - Epidemiological evidence increasingly points to exogenous or endogenous
      oestrogens as a risk factor for breast cancer. However, it is unlikely that
      induction of oestrogen-dependent tumour growth is the sole contribution of
      oestrogens to tumour development in the mammary gland, because oestrogen
      receptors are barely detectable in normal mammary epithelial cells. In this
      review, I examine a mechanism for mammary carcinogenesis, which emphasizes tumour
      initiation by metabolic activation of oestrogens in combination with cell
      transformation and growth stimulation by oestrogen receptor-mediated processes.
      Catecholestrogen metabolites are capable of metabolic redox cycling between
      quinone and hydroquinone forms, a mechanism of free radical generation. Several
      types of direct and indirect free radical-mediated DNA damage are induced by
      oestrogens in vitro and in vivo, such as DNA single strand breaks, 8
      hydroxylation of guanine bases, and DNA adduct formation by malondialdehyde, a
      decomposition product of free radical-induced lipid peroxides. The substrate for
      redox cycling and free radical generation may be 4-hydroxoestradiol, because this
      metabolite is formed from oestradiol by a specific oestrogen 4-hydroxylase
      detected in several human organs including mammary tissue. It has also been
      formed in organs of rodents where oestrogens induce tumours, with the exception
      of the liver. 4-Hydroxyoestradiol is a potent, long-acting oestrogen and may
      complete the carcinogenic process by stimulating receptor-mediated proliferation.
      An understanding of a possible mechanism of mammary carcinogenesis as a result of
      oestrogen-mediated initiation means that several prevention strategies, based on
      inhibiting metabolic activation of oestrogens or free radical action, can be
      developed.

PMID- 9161807
TI  - The distribution of leukaemia in association with domestic water quality in south
      west England.
AB  - This study assessed whether there is any variation in the incidence of
      haematological malignancies between geographical areas of differing water
      supplies in the South West peninsula of the United Kingdom (1984 to 1988
      inclusive). The possibility of correlations existing between variation in water
      quality and variation in the incidence of haematological malignancies was
      examined. Haematological incidence data, taken from the Leukaemia Research Fund's
      Data Collection Study, were mapped into 46 geographical areas of differing water
      supply. The distribution of the mapped cases was then tested for homogeneity
      using the Potthoff and Whittinghill (1966) test score. The age-adjusted incidence
      ratios calculated during the heterogeneity testing were examined for correlations
      with water quality indicators using correlation and stepwise regression.
      Significant heterogeneity in the incidence rates among water supply areas was
      observed for two groups of disease-acute leukaemias and myeloproliferative
      disorders. Three water quality indicators-pH, nitrate concentration and aluminium
      concentration-varied considerably over the study period. Significant correlations
      were observed between the standardized incidence ratios of five disease
      categories and some water quality indicators, especially aluminium and
      trihalomethane concentrations. The standardized incidence ratios of some
      haematological malignancies differed between geographical areas of water supply
      in South West England, and the evidence suggests that this variation may be
      associated with variation in water quality indicators. Although this lends
      support to similar findings in the United States of America, the pattern of
      correlations are affected by disease latency and statistical methodology.

PMID- 9161808
TI  - Risk of stomach cancer in patients with gastric or duodenal ulcer.
AB  - It has been suggested that the risk of stomach cancer is increased when there is
      a history of gastric ulcer, but decreased in those with a history of duodenal
      ulcer. To provide further information on the issue, data from a case-control
      study of gastric cancer conducted in greater Milan, northern Italy, between 1985
      and 1993, were examined. There were 746 cases of gastric cancer below the age of
      75 and 2,053 controls admitted to hospital for acute, non-neoplastic, non-hormone
      related diseases. A total of 76 (10.2%) cases and 84 (4.1%) controls reported a
      history of gastric ulcer, corresponding to a multivariate odds ratio (OR) of 2.6
      (95% confidence interval, CI = 1.8-3.6). Fifty nine cases (7.9%) and 111 (5.4%)
      controls reported a history of duodenal ulcer, corresponding to an OR of 1.3 (95%
      CI = 0.9-1.8). The OR of gastric cancer was significantly above unity for the
      first five years after diagnosis of gastric ulcer (OR = 7.4, 95% CI 3.7-14.8),
      and declined thereafter. No consistent pattern of risks was observed after
      duodenal ulcer. The present data therefore confirm that the risk of gastric
      cancer is increased after gastric ulcer. They do not support, however, a reduced
      risk after duodenal ulcer. This may be due to variable baseline characteristics
      of the populations studied, or to the different role and impact of Helicobacter
      pylori and other determinants of duodenal ulcer and gastric cancer in various
      countries.

PMID- 9161809
TI  - Time trends in oesophageal cancer incidence in Cote d'Or (France), 1976-93.
AB  - The purpose of this study was to examine the change in incidence pattern of
      oesophageal cancer in the Cote-d'Or region (Burgundy, France). Data from the
      population-based cancer registry were used to study time trends between 1976 and
      1993, according to sex, place of residence, subsite and histology. There was a
      non-significant increase in incidence of oesophageal cancer, by an average of
      +1.0% [confidence interval:-0.7; +2.8] per year in men and +2.0% [CI: -3.0; +6.9]
      in women. In men, variations in incidence were minor according to subsite and
      place of residence, among the six age groups studied. In contrast, there were
      important changes among histological types. Rates of squamous cell carcinoma
      remained stable, but those of adenocarcinoma increased significantly (P < 0.001).
      They represented 5.6% of known histological types, between 1976 and 1987, and
      20.1% in 1991-3. Similar trends were observed in women. This rising incidence of
      adenocarcinomas, observed later than in the UK or the USA, started in 1987-90 and
      was particularly pronounced between 1991 and 1993. In view of this sharp increase
      in incidence of oesophageal adenocarcinomas, research on their aetiological
      determinants is urgently needed.

PMID- 9161810
TI  - Migration within Spain, level of education, and cervical cancer screening.
AB  - Migration has been related to the utilization of preventive care services. We
      analysed the relation between cervical cancer screening and migration within the
      same country and socioeconomic status in a context in which there is no organized
      screening. The health survey of Barcelona (Spain) was the data source. Barcelona,
      a city in north eastern Spain, has experienced important migration from the south
      and other regions of Spain. Variables studied were the migrant women's year of
      arrival, age at arrival, educational attainment and Pap smear test uptake.
      Multivariate logistic regression analysis was performed to examine the
      correlations among the variables of interest. Just over 30% of the women had
      never had a Pap smear test. Uptake was higher among younger, educated women born
      either in Barcelona or abroad. After adjusting for age, migrant women were at
      higher risk for not participating in screening tests (odds ratio: 1.23; 1.09
      1.39); but after adjusting for educational attainment and age, the odds ratio was
      no longer significant. This study shows that migrants within Spain have less
      access to preventive services, such as cervical cancer screening in an
      opportunistic setting. However, this association is almost completely explained
      by socioeconomic status. Migration could be seen as a social factor that puts
      people at risk of falling into lower socioeconomic status associated with poor
      access to screening.

PMID- 9161811
TI  - The risk factor profile of recto-sigmoid adenomas: a prospective screening study
      of 665 patients in a clinical rehabilitation centre.
AB  - During a prospective screening study for recto-sigmoid adenomatous polyps, the
      influence of the following risk factors was evaluated: age; gender; body mass
      index; heredity for colorectal malignancy; diabetes; hypertension; constipation;
      previous gastric surgery; previous gastric acid inhibition; alcohol and cigarette
      consumption; serum cholesterol; serum triglycerides; and serum gastrin. Screening
      fibre-sigmoidoscopy of 665 patients (aged between 50 and 60 years) at a clinical
      rehabilitation centre for gastrointestinal and metabolic diseases showed that 146
      had one or several adenomas. The study population was overweight by a mean of
      about 15%. Comparison of those with and those without adenoma using univariate
      analysis, showed that the group with adenomas had higher serum triglyceride
      values, drank more alcohol on a regular or excessive basis, were more frequent
      smokers, and had a tendency to raised fasting serum glucose. In a multivariate
      analysis, age, high serum triglycerides and high alcohol consumption were risk
      factors for recto-sigmoid adenomas. The risk factor profile identified in this
      study may help in the selection of individuals for screening sigmoidoscopy from a
      similar background population. It also identifies target conditions for primary
      prevention of colorectal neoplasia.

PMID- 9161812
TI  - Factors affecting compliance with colorectal cancer screening in France:
      differences between intention to participate and actual participation.
AB  - This study aimed to identify the social, cultural and psychological
      characteristics influencing behaviour in a cancer mass screening campaign in a
      French population. The intention to take a screening test and actually doing it
      was studied, in particular. A self reported-questionnaire was mailed in December
      1992 to a random sample of people living in Caen (western France), and aged from
      45-74 years. The sample was formed by random selection from electoral registers.
      The study was population based, in the Caen area, department of Calvados, France.
      The questionnaire comprised 26 open and close questions. Starting in February
      1993, the occult blood screening test (haemoccult IIR) for colorectal cancer was
      offered by general practitioners (GPs), occupational health doctors and
      pharmacists in the Caen area to all those aged 45-74 years. From 1 February 1993
      to 30 June 1994, the data on the mass screening campaign were centralized and the
      study population divided into those who took the screening test and those who did
      not. Of the 1,129 persons contacted, 645 (57.1%) returned the questionnaire.
      After exclusions, 585 questionnaires were used for analysis. The results show
      that whether a person will actually take a screening test cannot be predicted
      from their intention to do so. The sociodemographic and cultural characteristics
      influencing the intention to take the test differ from those influencing
      execution of the test. Among the variables tested here, the following four
      sociodemographic and cultural characteristics were independently predictive of
      actually taking the screening test for colorectal cancer: compliance with the
      health insurer's advice; low or medium sociodemographic status, living with a
      partner (or widowhood); and not knowing someone with cancer. The analysis of the
      quantitative and qualitative differences between the intention to take the test
      and actually doing it could elucidate the reasons underlying refusal. Poor
      screening compliance has multiple causes. A record of intention to take a
      screening test alone is not appropriate. This type of study should no longer be
      carried out to determine the mechanisms underlying behaviour towards secondary
      prevention.

PMID- 9161813
TI  - The ability of two cooked food mutagens to induce aberrant crypt foci in mice.
AB  - The aberrant crypt foci assay has been used extensively to study different
      compounds for chemopreventive action, but almost all investigations have used
      initiators not normally found in the diet. In the present study two food-borne
      initiators, 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6
      phenyl-imidazo[4,5-b]pyridine (PhIP) were used. To simulate the human exposure
      further, we chose a feeding regimen with continuous low IQ- and PhIP-doses.
      Throughout the study female mice were given diets with or without 0.03% IQ or
      0.03% PhIP. Two additional groups were given azoxymethane (AOM) (5 mg/kg body
      weight) and 1,2-dimethylhydrazine dihydrochloride (DMH-2HCl) (20 mg/kg body
      weight), respectively, one dose a week for two weeks. Animals were killed after
      four and 10 weeks. After four weeks only the mice dosed with IQ and PhIP had
      aberrant crypt foci. A much higher number of aberrant crypt foci were found in
      the IQ mice (31.8 +/- 5.2) than in the PhIP mice (0.5 +/- 0.3). After 10 weeks
      aberrant crypt foci were found in all dosed groups. The IQ mice had significantly
      more (P < or = 0.001) small and total aberrant crypt foci than the other groups.
      AOM and DMH induced a higher percentage of medium or large sized aberrant crypt
      foci than PhIP or IQ. The interpretation of the aberrant crypt foci as precursor
      lesions for colon cancer in the PhIP and IQ mice is difficult because PhIP and IQ
      have not been reported to be colonic carcinogens. If cooked food mutagens such as
      IQ or PhIP are to be used as initiators in the aberrant crypt foci test, the use
      of rats may be preferable.

PMID- 9161815
TI  - Time trends in diagnostic strategy, treatment, and prognosis of gastric cancer in
      the elderly: a population based study.
AB  - The impact of changes in diagnostic strategies for gastric cancer and attitudes
      towards surgery in elderly patients is not known. A population-based series of
      842 gastric cancers diagnosed between 1976 and 1993 in patients aged 70 and older
      in Cote-dOr, France, was used to establish trends in diagnostic strategy,
      treatment, and prognosis. The use of endoscopy alone increased from 3% (1976-78)
      to 81% (1991-93). This trend was initially associated with a decrease in the use
      of x-ray alone, then with a decrease in the use of both x-ray and endoscopy. The
      proportion of resection for cure increased from 26% during 1976-78 to 43% during
      1991-93 (P < 0.001). The proportion of cancers not extending beyond the gastric
      wall increased from 12% to 24% (P < 0.05). Operative mortality decreased from
      38.7% (1976-78) to 13.3% (1991-93) and the corresponding 3-year crude survival
      rate rose from 7% to 18%. Improvements in the care of gastric cancer in elderly
      patients have been achieved, but further progress is warranted.

PMID- 9161814
TI  - Vanadium-mediated chemoprotection against chemical hepatocarcinogenesis in rats:
      haematological and histological characteristics.
AB  - The trace element vanadium was investigated for its anti-neoplastic role in
      relation to haematological status, hepatic histopathology and histochemical
      analysis of glycogen in liver. Its impact on the survival of male Sprague-Dawley
      rats subjected to a two-stage hepatocarcinogenesis regimen was also assessed.
      Initiation was performed using a single intraperitoneal injection of
      diethylnitrosamine (DENA) (200 mg/kg) followed by promotion with phenobarbital
      (0.05%) in a basal diet. Vanadium supplementation as ammonium monovanadate at 0.5
      ppm vanadium in drinking water was given ad libitum throughout the experiment (20
      weeks), before the initiation (4 weeks), or during the promotional period (14
      weeks). At the end of the study, there was a significant decrease in red blood
      cell count, haemoglobin content, haematocrit value, mean corpuscular haemoglobin,
      mean corpuscular haemoglobin concentration, plasma volume change and total white
      cell count, with a concurrent alteration in lymphoid:myeloid ratio in DENA
      control animals compared with their normal counterparts. Vanadium supplementation
      throughout the study or before the initiation significantly reversed the DENA
      induced alterations in most of the haematological indices. A single
      intraperitoneal injection of DENA also depleted the plasma albumin concentration,
      raised the plasma globulin content, and decreased the ratio of albumin to
      globulin. These altered features began to return to normal following vanadium
      supplementation. Supplementary vanadium also elicited substantial protection
      against DENA-mediated rat liver carcinogenesis. This was fairly evident from
      hepatic histology and evaluation of glycogen accumulation by periodic acid-Schiff
      reaction. The survival of DENA-treated animals was considerably increased in the
      presence of vanadium. The critical involvement of vanadium in modulating several
      factors associated with erythropoiesis under carcinogenic challenge may thus have
      a possible impact on the eventual increased survival of the host.

PMID- 9161816
TI  - OESO World 5th Congress Paris, September 1996.

PMID- 9161817
TI  - International Meeting on Cancer Chemoprevention: molecular basis, mechanisms and
      trials.

PMID- 9161818
TI  - Extra low frequency electric and magnetic fields in the bedplace of children
      diagnosed with leukaemia: a case-control study.

PMID- 9161819
TI  - AIDS turnaround: first remedy the adverse effects of the condom policy.

PMID- 9161820
TI  - Why quality matters--even to the publisher.

PMID- 9161821
TI  - Introduction of a computerised protocol in clinical practice: is there anything
      to gain?
AB  - OBJECTIVES: To assess the potential benefit of a protocol for the diagnostic work
      up and management of patients with obstructive jaundice, by comparing its
      recommendations with the policies actually followed in patients and to compare
      local expertise with diagnostic and therapeutic procedures with that described in
      published reports. DESIGN: A retrospective analysis of patients' records.
      SETTING: University hospital, The Netherlands. SUBJECTS: 49 consecutive patients
      who presented to the departments of internal medicine and surgery between June
      1990 and June 1992 with serum alkaline phosphatase activities > 125 mumol/L, and
      serum bilirubin concentrations > 17 mumol/L. MAIN OUTCOME MEASURES: The
      proportions of diagnostic and therapeutic decisions that deviated from the
      recommendations, and the success rates of diagnostic and therapeutic procedures.
      RESULTS: In patients with bile duct stones the treatment strategies did not
      deviate from those recommended in the protocol. In patients with cancer 38 (30%)
      of the 128 diagnostic decisions and 4 (11%) of the 37 therapeutic decisions
      deviated from the protocol. Success rates of all diagnostic investigations were
      comparable with those reported, and success rates of endoscopic biliary drainage
      tended to be lower than those reported. CONCLUSIONS: The introduction of a
      protocol for the diagnostic work-up of patients with obstructive jaundice may
      reduce unnecessary investigations and diagnostic omissions by half. Because local
      expertise of some of the procedures seems to be significantly less than reported
      elsewhere it may be necessary to modify the protocol to better fit local
      circumstances.

PMID- 9161823
TI  - Repair of incisional hernias with expanded polytetrafluoroethylene.
AB  - OBJECTIVE: To find out the rates of recurrence after repair of incisional hernias
      with or without the implantation of a PTFE-patch. DESIGN: Open and retrospective
      study. SETTING: University hospital, Austria. SUBJECTS: 26 patients who had their
      incisional hernias repaired with a polytetrafluoroethylene (PTFE) patch and 70
      for whom conventional methods were used. MAIN OUTCOME MEASURES: Absolute
      recurrence rate and the Kaplan-Meier estimate 24 months after the operation.
      Presence of risk factors. RESULTS: Three patients developed recurrences by 24
      months in the PTFE group and 41 in the conventional group. The Kaplan-Meier
      estimate for the PTFE group was 13% and for the conservative group 63%. Women had
      significantly fewer recurrences than men (p < 0.05). Age, body mass index, and
      diameter of the defect were not significantly associated with an increased risk
      of failure. CONCLUSIONS: Insertion of a prosthesis can improve the results of
      surgical repair of incisional hernias.

PMID- 9161822
TI  - Papillary thyroid microcarcinoma: clinical study and prognosis.
AB  - OBJECTIVE: To study the anatomical and prognostic characteristics of papillary
      thyroid microcarcinomas (10 mm or less in size). DESIGN: Retrospective review.
      SETTING: Community hospital, Spain. SUBJECTS: 36 patients with papillary
      microcarcinomas diagnosed over a period of 20 years from a total of 158 papillary
      carcinomas with complete follow-up. MAIN OUTCOME MEASURES: Symptoms, treatment,
      histopathological confirmation and follow-up compared with those of papillary
      carcinomas more than 10 mm in size. RESULTS: Six of the patients with
      microcarcinomas presented with adenopathy, the remaining 30 being admitted for
      treatment of associated thyroid diseases. In 15 cases the tumour was 5 mm or less
      in size. Thirty were well-differentiated, 2 were follicular, and 2 showed signs
      of diffuse sclerosis. Three had recurred after total thyroidectomy, but no
      patient died. When the results were compared with those of the patients with
      larger tumours, we found differences in histological type (p = 0.001), the
      incidence of adenopathy (p = 0.03), TNM stage (p = 0.001) and mortality (p =
      0.04). CONCLUSIONS: There are clinical, histopathological, and prognostic
      differences between microcarcinomas (which do well) and larger papillary tumours.

PMID- 9161824
TI  - Complications of laparoscopic cholecystectomy in Hungary: a multicentre study of
      13,833 patients.
AB  - OBJECTIVE: To report our countrywide experience of laparoscopic cholecystectomy
      with particular reference to complications. DESIGN: National multicentre
      retrospective study. SETTING: 71 university departments and public hospitals in
      Hungary. SUBJECTS AND INTERVENTIONS: 13,833 patients operated on between 1
      January 1990 and 31 December 1993. Follow up by questionnaire. RESULTS: 732
      patients (5.3%) required conversion to open cholecystectomy, urgently because of
      intraoperative complications in 204 (1.5%), electively for acute or chronic
      inflammation or obscure anatomy in 441 (3.2%), for unexpected findings in 72
      (0.5%) and for technical problems in 15 (0.1%). There were postoperative
      complications in 598 (4.3%) but reoperation was indicated in only 154 patients
      (1.1%). There were bile duct injury in 81 (0.6%) and 199 bleeds (1.4%) which
      required conversion in 102 patients (0.7%) and reoperation in 38 (0.3%). 36 of
      the 181 postoperative recognized bile leaks required reoperation (20%). 19
      patients died (0.1%). CONCLUSIONS: The morbidity and the mortality of
      laparoscopic cholecystectomy are better than after the open operation. The 2-6
      times higher risk of bile duct injury mentioned in early studies was not
      confirmed.

PMID- 9161825
TI  - Surgical treatment and its long-term result for caustic-induced prepyloric
      obstruction.
AB  - OBJECTIVE: To present our long-term results of the treatment of caustic-induced
      prepyloric obstruction, and to set out guidelines for the management of such
      patients. DESIGN: Retrospective study. SETTING: General hospital (medical
      centre), Taiwan. SUBJECTS: 30 patients (8 male and 22 female, mean age 34 years,
      range 13-62) who developed prepyloric obstruction out of 271 treated for caustic
      injuries of the upper gastrointestinal tract. INTERVENTIONS: Gastrojejunostomy (n
      = 24), antrectomy and Billroth I reconstruction (n = 4), and antrectomy and
      Billroth II reconstruction (n = 2). Four patients required second operations:
      oesophageal reconstruction for stricture (n = 3), and gastrojejunostomy for
      restenosis of Billroth I anastomosis (n = 1). MAIN OUTCOME MEASURES: Morbidity
      and mortality. RESULTS: No patient died postoperatively, and there were three
      complications--wound infection, internal bleeding, and stenosis of the Billroth I
      anastomosis. 21 patients were able to enjoy their normal diet postoperatively, 5
      required periodic dilatation of oesophageal strictures, and 4 required further
      operations. CONCLUSIONS: Gastrojejunostomy gives good long term results as long
      as there is no oesophageal stricturing, and morbidity and mortality are low. The
      long term outcome is dependent on the degree of oesophageal involvement.

PMID- 9161826
TI  - Seven year results of vertical banded gastroplasty for morbid obesity.
AB  - OBJECTIVE: To present our experience with a group of obese patients treated by
      vertical banded gastroplasty. DESIGN: Open prospective study. SETTING: Teaching
      hospital, Sweden. SUBJECTS: 198 Morbidly obese patients operated on between 1986
      and April 1994. INTERVENTIONS: Modified Mason vertical banded gastroplasty. MAIN
      OUTCOME MEASURES: Weight loss, mortality, early and late morbidity, and
      reoperation. RESULTS: The mean (SEM) age was 40 (0.7) and 149 of the 198 were
      women (75%). 22 Patients (11%) were lost to follow-up. Five patients died (3%),
      one soon after operation. Mean (SEM) body mass index (BMI) was 44.4 (0.5)
      preoperatively and this decreased to 32.6 (0.6) after four years (n = 99) and
      33.8 (1.3) after seven years (n = 20). 21 patients developed 24 early
      postoperative complications, and 31 patients were reoperated on 41 times for late
      complications. CONCLUSION: All patients lost weight after vertical banded
      gastroplasty, and their weight continued to decrease during a seven-year follow
      up. This was somewhat offset by the high rate of reoperations required.

PMID- 9161827
TI  - Evaluation of human collagen biomaterials in the healing of colonic anastomoses
      in dogs.
AB  - OBJECTIVE: To investigate the ability of human collagen biomaterials to secure
      colonic anastomoses in dogs and to evaluate the biocompatibility of anastomotic
      protection patches (APP). DESIGN: Experimental open study. SETTING: Experimental
      research centre, France. MATERIAL: 21 mongrel dogs randomised into three groups
      of 7 each. INTERVENTION: Standard transverse colonic end-to-end anastomoses were
      secured with two-layer oxidised collagen I + III sponge covered with thin
      crosslinked collagen IV film (APP 1) glued around the suture (n = 7); two-layer
      oxidised collagen I + III sponge covered with thin non-crosslinked collagen I +
      III film patch (APP 2) (n = 7); or sealed by fibrin sealant (n = 7), which acted
      as a controls. MAIN OUTCOME MEASURES: Gross examination, radiological control
      (barium enemas), and microscopic examination on day 35 postoperatively. RESULTS:
      Gross clinical and radiological examinations on day 35 showed normal wound
      healing in all but one dog in which the anastomoses had occluded by day 16. There
      was significantly less stricturing with the APP 2 patch (p < 0.05 compared with
      the controls). Microscopic examination showed complete absorption of the APP 2
      patches as well as quicker mucosal and extracellular matrix repair than controls.
      The APP 1 patch gave the best healing of the muscular layer but did not reduce
      anastomosis stricturing, and was not totally absorbed. CONCLUSIONS: Collagen
      supporting devices do not alter healing of the large bowel. Encircling patches do
      not increase the number of adhesions or the rate of anastomotic stricturing and a
      thin fibrillar collagen I + III dense layer may even improve it. The speed of
      absorption of the patch depends on the type of dense collagen film. These results
      argue for a prospective clinical evaluation in humans.

PMID- 9161828
TI  - Changes in hepatic portal resistance and in liver morphology during regeneration:
      in vitro study in rats.
AB  - OBJECTIVE: To study the effects of liver regeneration on hepatic portal
      resistance and on the morphology of liver sinusoids. DESIGN: Experimental in
      vitro study. SETTING: University laboratory, Hong Kong. ANIMALS: 10 Groups of 6
      male Sprague Dawley rats each. INTERVENTIONS: Two thirds hepatectomy, with
      subsequent re-hepatectomy for measurements 0, 1, 3, 7, 21 and 56 days later.
      Perfusion of isolated livers and histomorphometry. MAIN OUTCOME MEASURES: Hepatic
      portal resistance and measurement of width and length of sinusoids. RESULTS:
      Liver weight was restored within 7 days of hepatectomy. Hepatic portal
      resistance/g of liver increased, reaching a maximum at 3 and 7 days of
      hepatectomy, and subsequently returned to initial values after 56 days. Width of
      sinusoids decreased to a minimum within 3 to 7 days of hepatectomy, and
      subsequently returned close to initial values within 56 days of hepatectomy. The
      changes in hepatic portal resistance occurred in phase with the changes in the
      width of liver sinusoids. CONCLUSIONS: There is a transient increase in hepatic
      portal resistance/g of liver during regeneration; transient narrowing of
      sinusoids may contribute to this change.

PMID- 9161829
TI  - A simple technique for obturator hernia repair.

PMID- 9161830
TI  - Pseudoaneurysm of the cystic artery.

PMID- 9161831
TI  - Bronchogenic cyst: a rare cause of a retroperitoneal mass.

PMID- 9161832
TI  - Outcome of incidental adrenal masses not operated on: 44 cases over 7 years.

PMID- 9161833
TI  - Expression of beta 2-integrins and L-selectin on polymorphonuclear leukocytes in
      septic patients.
AB  - Adhesion molecules on polymorphonuclear leukocytes (PMNL) play an important role
      in nonspecific defense mechanisms directed at invading microorganisms. When local
      infection, however, cannot be controlled, a systemic inflammatory response
      syndrome (SIRS) ensues which may progress to septic shock and multiple organ
      failure, these being major determinants of the patient's outcome. In the present
      study, the expression of beta 2-integrins and L-selectin on blood PMNL was
      measured on subsequent days in patients with sepsis (n = 17) and in healthy
      volunteers (n = 15). beta 2-Integrins and L-selectin molecules were detected by
      flow cytometry, using the monoclonal antibodies IB4 (anti-CD18) and Dreg200 (anti
      CD62L), respectively. Adhesion molecules were determined at baseline immediately
      after blood collection and also 45 min after incubation of cells in vitro at body
      temperature to allow for spontaneous regulation. In addition, PMNL were activated
      by receptor-dependent and receptor-independent stimuli to characterize stimulus
      specific adhesion molecule expression. In parallel with the measurement of
      adhesion molecules, severity of sepsis was assessed by the Elebute score. The
      results demonstrate significant differences in the basal, spontaneous and
      stimulus-induced expression of adhesion molecules between healthy volunteers,
      survivors (n = 11) and nonsurvivors (n = 6). Moreover, when survivors and
      nonsurvivors with severe sepsis (Elebute score > 12) were compared, basal
      expressions of both beta 2-integrins and L-selectin were significantly lower in
      patients who did not survive. Thus, measurement of adhesion molecules on
      circulating PMNL may be useful to identify septic patients at high risk for
      lethal outcome.

PMID- 9161834
TI  - The role of splenic macrophages in plasma tumor necrosis factor levels in
      endotoxemia.
AB  - We investigated the function of splenic macrophages (M phi s) with respect to
      changes in plasma tumor necrosis factor (TNF) in lethally endotoxemic rats
      treated with gadolinium chloride (GdCl3), which blocks the phagocytosis of large
      liver M phi s. We also carried out an immunohistochemical study to investigate
      the change of populations of liver and splenic M phi s under the condition of
      dysfunction of liver M phi s with or without splenectomy. Twenty-four-hour
      survival rates were 100% in the GdCl3-treated group (n = 6) and 0% in the
      nontreated group (n = 6). These rates did not change with splenectomy.
      Immunohistochemical examination with the primary monoclonal antibodies ED1, ED2
      and ED3 revealed that large liver M phi s were eliminated after GdCl3 injection,
      and that this was not related to splenectomy. The splenic M phi s were not
      affected by GdCl3 treatment. Plasma TNF levels did not differ between the GdCl3
      treated and the nontreated groups, irrespective of whether splenectomy was
      performed. It was suggested that plasma TNF levels are not affected by the
      splenic M phi s and that they do not compensate for dysfunction of liver M phi s
      after GdCl3 treatment.

PMID- 9161835
TI  - The effect of vitamin C and vitamin E supplementation on bacterial translocation
      in chronic portal hypertensive and common-bile-duct-ligated rats.
AB  - In rats with chronic portal hypertension (PH) and common bile duct ligation
      (CBDL), significant ileal bacterial overgrowth, translocation of indigenous
      intestinal bacteria, a decrease in hepatic and ileal reduced glutathione (GSH)
      and an increase in ileal mucosal lipid peroxidation occur. alpha-Tocopherol
      (vitamin E) and ascorbic acid (vitamin C) treatment attenuated the incidence of
      bacterial translocation, improved hepatic and ileal GSH levels and decreased
      ileal mucosal lipid peroxidation. These results suggest that in chronic PH and
      CBDL oxidative processes in the liver and intestine play an important role for
      bacterial translocation.

PMID- 9161836
TI  - New technique for inducing reversible obstructive jaundice in the rat.
AB  - We present a new animal model of reversible obstructive jaundice, in which two
      polyethylene tubes were inserted into the common bile duct, one towards the liver
      and the other towards the duodenum. The ends of the tubes were tunneled
      subcutaneously and tied shut to establish obstructive jaundice. Biliary drainage
      was achieved without a second laparotomy by connecting the tubes with a 1-cm
      segment of a 24-gauge needle. Serum concentrations of total bilirubin (TB),
      glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT),
      alkaline phosphatase (ALP), and albumin (Alb.) were measured before and after
      obstruction and decompression. TB, GOT, GPT and ALP increased and Alb. decreased
      7 days after the onset of biliary obstruction. All values normalized 14 days
      after biliary drainage at the latest. Our model is reproducible and allows for
      evaluation of biliary decompression. Unlike previous models, it can be used for
      long-term investigation of chronic obstructive jaundice.

PMID- 9161837
TI  - Evaluation of scolicidal agents in an experimental hydatid disease model.
AB  - INTRODUCTION: The treatment of hydatid disease is largely surgical, with medical
      treatment being reserved as coadjuvant treatment. The scolicidal agents have
      been, and are being used mainly during surgical manipulation of the cysts, with
      the object of avoiding relapses and peritoneal dissemination. OBJECTIVE:
      Evaluation of the scolicidal agents used in surgery in a hydatid disease model in
      the mouse. MATERIAL AND METHODS: We have used 85 Swiss OF1 mice, weighing more
      than 30 g, of 90 +/- 10 days of age, in which a picture of hydatid sowing was
      reproduced by means of intra-peritoneal inoculation with 0.2 ml of a suspension
      which contained approximately 1,200 viable protoscolex of Echinococcus granulosus
      which came from the livers of parasite-infested sheep. 24 h after the
      inoculation, the mice were subjected to a median laparotomy for the introduction
      of 1 ml of the scolicidal solution to be evaluated: physiologic saline (n = 10);
      10% povidone iodine (n = 15); praziquantel (n = 15); 10% hydrogen peroxide (n =
      15); 10% hypertonic saline (n = 15); simulated operation (n = 15). After 7 months
      of follow-up, the mice were sacrificed and the following was evaluated: number of
      isolated cysts, cyst masses, and total cysts. RESULTS: The number of isolated
      cysts which developed was significantly lower in the hydrogen peroxide group (tF
      2.14 < RC 3.29). The number of cyst masses was significantly reduced in the
      hydrogen peroxide group (tF 2.14 < RC 2.18), in the povidone iodine group (tF
      2.17 < RC 3), and in the hypertonic saline group (tF 2.11 < RC 2.77). The total
      number of cysts which developed decreased significantly in the hydrogen peroxide
      (tF 2.14 < RC 2.84) and the povidone iodine (tF 2.17 < RC 3.79) groups.
      CONCLUSIONS: Hydrogen peroxide and povidone iodine show a greater protoscolicidal
      effect than simple cleansing with physiological saline, hypertonic saline, or
      praziquantel.

PMID- 9161838
TI  - Osteopenia following total gastrectomy in the rat--state of mineral metabolism
      and bone histomorphometry.
AB  - Total gastrectomy (GX) in humans is frequently followed by osteopenia, but the
      details are unclear. The present investigations in the rat were aimed at
      elucidating its pathogenesis. Seventeen weeks after GX, we evaluated Ca, Mg and P
      metabolism as well as bone parameters, including fluorochrome-based bone
      histomorphometry. In GX rats, fecal Mg was increased, but intestinal absorption
      of P, Ca, and Mg was within normal limits, as was the urinary excretion of Ca,
      Mg, hydroxyproline and the pyridinium cross-links. In contrast, urinary P as well
      as cyclic AMP were significantly increased. In serum of GX rats, gastrin and 25
      hydroxyvitamin D (25-OHD) were decreased, and Ca, Mg, P, parathyroid hormone
      (PTH), calcitonin, and the bone marker osteocalcin were normal, whereas 1,25
      dihydroxyvitamin D [1,25(OH)2D] was significantly increased. GX rats had
      significantly reduced bone density and mineral content, severe high-turnover
      osteopenia, characterized by normal width but significantly decreased maturation
      time of osteoid, increased bone formation rate, and increased numbers of
      osteoclasts. We concluded that after GX (1) there is high-turnover osteopenia
      with normal mineralization and other histomorphometric features resembling those
      seen in states with hyperphosphaturia and subsequent hypervitaminosis D; (2)
      normal serum PTH levels and several indirect indicators of parathyroid gland
      function argue against the presence of (secondary) hyperparathyroidism, whereas
      increased bone mobilization due to elevated 1,25(OH)2D explains the maintenance
      of homeostasis of serum minerals, especially Ca, at the expense of bone mineral;
      (3) a complex interplay of mineral-metabolic effectors exists, among which low 25
      OHD-PTH-independent renal phosphate losses, and high 1,25(OH)2D are prominent
      features. The presented animal model is recommended for future research in this
      area.

PMID- 9161840
TI  - Cardioprotective effects of diltiazem during acute rejection on heterotopic heart
      transplants.
AB  - In the presence of severe rejection, cardiac allograft perfusion has been shown
      to be impaired. Since a functionally reversible vasoconstrictor component has
      been identified in this condition and rejection does not reverse if ischemia does
      not, we hypothesized that diltiazem may be beneficial in this condition.
      Experiments were performed on dogs with heterotopic heart transplants and chronic
      instrumentation for the assessment of allograft perfusion. Two groups of cardiac
      allograft recipients were studied: untreated recipients and recipients treated
      with the calcium antagonist diltiazem (180 mg twice daily, orally). Allograft
      blood flow was monitored daily along with plasma diltiazem levels. The
      lymphoproliferative response to mitogens was studied at selected intervals until
      terminal rejection. Contractile function of the graft was assessed daily by
      palpation. Without immunosuppression, terminal rejection was observed within 7
      days. Rejection was confirmed by histology; cellular infiltration and myocyte
      necrosis were present in all cardiac allografts but to a significantly lesser
      degree in diltiazem-treated recipients. The mean blood flow of heterotopically
      implanted hearts was in the range of 35-50 ml/min, which decreased steadily in
      untreated recipients. In contrast, significant improvement of allograft perfusion
      was observed in diltiazem-treated recipients at days 4-6 after transplantation.
      Diltiazem also significantly attenuated mitogen-induced lymphocyte proliferation
      at peak sensitivity (2 days after transplantation). Diltiazem plasma
      concentrations were in the therapeutic range (30-60 ng/ml) before and after
      cardiac transplantation. Results of the present study demonstrate beneficial
      effects of diltiazem in the course of severe cardiac rejection. Such findings
      support its use during rejection when maintenance of graft blood flow and myocyte
      protection may be important for myocardial function and viability.

PMID- 9161839
TI  - Effect of thyroid hormone on urinary excretion of epidermal growth factor.
AB  - Thyroid hormones were demonstrated to upregulate the synthesis of epidermal
      growth factor (EGF) mRNA and proEGF in the kidneys in vivo. This prospective
      study was performed to examine the extent of the hypothyroid state in modulating
      EGF excretion in the urine (U-EGF; n = 23). Patients with thyroid cancer were
      serially followed up from the euthyroid status, which was retained by thyroxine
      supplement after thyroidectomy, to the hypothyroidism in preparing for 131I whole
      body scanning. Paired thyroid function panel, including triiodothyronine (T3),
      thyroxine (T4), thyroid-stimulating hormone (TSH), and U-EGF levels were measured
      on a weekly basis. Logarithmically transformed values of U-EGF were inversely
      correlated with TSH serum levels (p = 0.0000), but positively associated with T4
      levels (p = 0.0005). No apparent correlation was observed with the T3 serum
      content, age and gender of the patients (p > 0.1, respectively). If the interval
      of measurement was taken into consideration, serum TSH was the most significant
      factor in association with U-EGF (p = 0.0003). Our data indicate that excretion
      of EGF in human urine depends substantially upon thyroid hormone support.

PMID- 9161841
TI  - Immunocytochemical localization of copper,zinc superoxide dismutase in
      peroxisomes from watermelon (Citrullus vulgaris Schrad.) cotyledons.
AB  - In previous works using cell fractionation methods we demonstrated the presence
      of a Cu,Zn-containing superoxide dismutase in peroxisomes from watermelon
      cotyledons. In this work, this intracellular localization was evaluated by using
      western blot and EM immunocytochemical analysis with a polyclonal antibody
      against peroxisomal Cu,Zn-SOD II from watermelon cotyledons. In crude extracts
      from 6-day old cotyledons, analysis by western blot showed two cross-reactivity
      bands which belonged to the isozymes Cu,Zn-SOD I and Cu,Zn-SOD II. In peroxisomes
      purified by sucrose density-gradient centrifugation only one cross-reactivity
      band was found in the peroxisomal matrix which corresponded to the isozyme Cu,Zn
      SOD II. When SOD activity was assayed in purified peroxisomes two isozymes were
      detected, Cu,Zn-SOD II in the matrix, and a Mn-SOD in the membrane fraction which
      was removed by sodium carbonate washing. EM immunocytochemistry of Cu,Zn-SOD on
      sections of 6-day old cotyledons, showed that gold label was mainly localized
      over plastids and also in peroxisomes and the cytosol, whereas mitochondria did
      not label for Cu,Zn-SOD.

PMID- 9161843
TI  - Effects of Photofrin photodynamic action on mitochondrial respiration and
      superoxide radical generation.
AB  - Cyanide-resistant respiration increases after irradiation of isolated
      mitochondria in the presence of Photofrin. This suggests an enhancement of
      electron leakage which has been evaluated by measuring superoxide radical
      formation in submitochondrial particles incubated with 6 micrograms/ml Photofrin
      in the medium and irradiated with increasing doses of light at 365 nm. After a
      dose of 4.5 kJ/m2 has been delivered, superoxide generation increases by a factor
      of approximately 2.5 at the level of NADH dehydrogenase and by a factor
      approximately 1.5 in the cyt bc1 region. These effects have been compared with
      changes observed in NADH-, succinate- and ascorbate-driven respiration and their
      implications discussed.

PMID- 9161842
TI  - Factors influencing the antioxidant activity determined by the ABTS.+ radical
      cation assay.
AB  - This study introduces a simple direct antioxidant assay, based on the reduction
      of the ABTS.+ radical cation, and compares it with the myoglobin/ABTS.+ assay.
      The methods give closely similar results, establishing that the antioxidants
      studied to date in the latter assay act by scavenging the ABTS.+ radical cation
      and not by inhibiting its formation through reduction of ferryl myoglobin or
      reaction with H2O2.

PMID- 9161844
TI  - Multicomponent spectroscopic investigations of salivary antioxidant consumption
      by an oral rinse preparation containing the stable free radical species chlorine
      dioxide (ClO2.).
AB  - A multicomponent evaluation of the oxidative consumption of salivary biomolecules
      by a commercially-available oral rinse preparation containing an admixture of the
      stable free radical species chlorine dioxide (ClO2.) with chlorite anion (ClO2-)
      has been investigated using high resolution 1H NMR spectroscopy. The results
      obtained demonstrated that ClO2. and/or ClO2- present in this preparation
      effected the oxidative decarboxylation of salivary pyruvate (to acetate and CO2).
      Experiments conducted on chemical model systems confirmed the oxidative
      decarboxylation of pyruvate by this oral rinse, and also demonstrated that urate,
      thiocyanate anion, and the amino acids cysteine and methionine (precursors to
      volatile sulphur compounds responsible for oral malodour), were oxidatively
      consumed. The biochemical, periodontal and therapeutic significance of the
      results are discussed.

PMID- 9161845
TI  - Oxidative tissue response promoted by 5-aminolevulinic acid promptly induces the
      increase of plasma antioxidant capacity.
AB  - The heme precursor 5-aminolevulinic acid (ALA), acting as a prooxidant, has been
      proposed to underlie the clinical manifestations of various porphyric disorders.
      Accordingly, ALA-generated oxyradicals where shown to cause oxidative lesions in
      biomolecules and isolated cell organelles and to release iron from ferritin. In
      rats, administered ALA triggered oxidative stress in liver, brain and red
      muscles. We now study the correlation between the plasma antioxidant capacity and
      tissue oxidative damage, after acute (one and two doses) and prolonged (eight
      doses) ALA treatment of rats (one dose of ALA = 40 mg/kg body weight). The in
      situ spontaneous chemiluminescence intensity increased 5-fold in brain, 50% in
      liver and 4-fold in soleus muscle upon two dose-treatment, indicating tissue
      response to oxidative injury by ALA. Chemiluminescence reached the highest
      intensity after one or two doses of ALA and decreased after eight doses in all
      tissues. The plasma trapping capacity, evaluated by the luminol/2-amidinopropane
      system, gave a parallel response: maximum values after two doses and decreased
      values after prolonged treatment. After eight doses, the ALA concentration was
      found to be 3-fold above the normal value in plasma, 48% higher in liver and 38%
      higher in total brain. These data indicate that the plasma antioxidant system
      responds to ALA treatment and is correlated with tissue chemiluminescence. In
      vitro studies showed that ALA does not interfere with the antioxidant plasma
      capacity, neither promoting oxidation of plasma elements nor binding to plasma
      proteins.

PMID- 9161846
TI  - Oxygen-dependent fragmentation of cellular DNA by nitric oxide.
AB  - Although active oxygen species and related metabolites, such as nitric oxide
      (NO), have been postulated to play important roles in the apoptosis of various
      cells, a precise mechanism leading to cell death remains to be elucidated.
      Recently we found that the lifetime of NO depends greatly on the concentration of
      environmental oxygen and that NO reversibly inhibits mitochondrial respiration
      and ATP synthesis; the inhibitory effect is stronger at physiologically low
      oxygen tension than under atmospheric conditions (Arch. Biochem. Biophys. 323, 27
      32, 1995). The present work describes the effects of the NO-generating agent, 1
      hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene (NOC 18) and oxygen tension on the
      respiration, ATP synthesis and apoptosis of HL-60 cells. When respiration was
      inhibited by NOC 18, cellular ATP levels decreased significantly and DNA
      fragmentation was elicited. Both events were enhanced by decreasing oxygen
      tension and suppressed by adding NO-trapping agents, such as 2-(4-carboxyphenyl)
      4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) and oxyhemoglobin.
      The fragmentation of cellular DNA was inhibited in a dose dependent manner by
      herbimycin A, a tyrosine kinase inhibitor. Fragmentation of the DNA of HL-60
      cells was also induced either by peroxynitrite, superoxide or hydroxyl radical by
      some mechanism which was diminished by lowering the oxygen tension. These results
      indicated that the decrease in cellular ATP and activation of tyrosine kinase
      might play important roles in NO-induced apoptosis particularly under
      physiologically low oxygen tensions.

PMID- 9161847
TI  - Ozonolysis of 2'-deoxycytidine: isolation and identification of the main
      oxidation products.
AB  - The ozone-mediated oxidation of 2'-deoxycytidine (dCyd) was investigated on the
      basis of final product identification. The oxidation reaction gave rise to five
      major modified nucleosides which were isolated and characterized on the basis of
      extensive 1H NMR and mass spectrometry measurements. The comparison with the
      current knowledge of the hydroxyl radical mediated oxidation reactions of 2'
      deoxycytidine in aerated aqueous solution, indicates that the formation of ozone
      oxidation products may be mostly explained by the opening of the pyrimidine C5-C6
      double bond. Thus, the formation of the identified products obtained by
      ozonolysis of 2'-deoxycytidine is accounted for by the initial generation of an
      ozonide.

PMID- 9161848
TI  - Kupffer cell function in thyroid hormone-induced liver oxidative stress in the
      rat.
AB  - The influence of thyroid hormone (L-3, 3', 5-triiodothyronine, T3) on Kupffer
      cell function was studied in the isolated perfused rat liver by colloidal carbon
      infusion. Rates of carbon uptake were determined from the influent minus effluent
      concentration difference and the flow rate, and the respective carbon-induced
      respiratory activity was calculated by integration of the area under the O2
      curves during carbon infusion. In the concentration range of 0.2 to 2.0 mg of
      carbon/ml, livers from euthyroid rats exhibited a sigmoidal-type kinetics of
      carbon uptake, with a Vmax of 4.8 mg/g liver/min and a concentration of 0.82
      mg/ml for half-maximal rate; carbon-induced O2 uptake presented a hyperbolic-type
      kinetics, with a Vmax of 4.57 mumol of O2/g liver and a K(m) of 0.74 mg of
      carbon/ml, which significantly correlates with the carbon uptake rates. Light
      microscopy showed that carbon was taken up exclusively by non-parenchymal cells,
      predominantly by Kupffer cells. Thyroid calorigenesis was found in parallel with
      increased rates of hepatic O2 consumption and thiobarbituric acid reactive
      substances (TBARS) formation, glutathione (GSH) depletion, and higher sinusoidal
      lactate dehydrogenase (LDH) efflux compared to control values. In the
      concentration range of 0.25 to 0.75 mg/ml, carbon infusion did not modify liver
      LDH efflux in control rats, while it was significantly enhanced in T3-treated
      animals. In this latter group, higher carbon concentrations (1 and 1.3 mg/ml) led
      to loss of viability of the liver. At 0.25 to 0.75 mg of carbon/ml, both the
      rates of carbon uptake and the associated carbon-induced respiratory activities
      were significantly increased by T3 treatment, effects that were abolished by
      pretreatment of the rats with gadolinium chloride (GdCl3). In addition, GdCl3
      decreased by 50% the changes induced by T3 in hepatic GSH content and TBARS
      formation. It is concluded that hyperthyroidism enhances Kupffer cell function,
      correlated with the increased number of liver macrophages observed
      histologically, which may represent an alternate source of reactive O2 species to
      that induced in parenchymal cells, thus contributing to the enhanced oxidative
      stress status developed.

PMID- 9161849
TI  - Cellular antioxidant properties of human natural killer enhancing factor B.
AB  - The protein, NKEF (natural killer enhancing factor), has been identified as a
      member of an antioxidant family of proteins capable of protecting against protein
      oxidation in cell-free assay systems. The mechanism of action for this family of
      proteins appears to involve scavenging or suppressing formation of protein thiyl
      radicals. In the present study we investigated the antioxidant protective
      properties of the NKEF-B protein overexpressed in an endothelial cell line
      (ECV304). Nkef-B-transfected cells displayed significantly lower levels of
      reactive oxygen species (ROS) compared with control or vector-transfected cells.
      Tert-Butylhydroperoxide-induced ROS was 15% lower in nkef-B-transfected cells and
      cytotoxicity was slightly, though not significantly, lower. NKEF-B had no effect
      on ROS induced by menadione or xanthine plus xanthine oxidase. NKEF-B
      overexpression resulted in slightly (approximately 10%) lower levels of cellular
      glutathione (GSH) and had no effect on rate or extent of GSH depletion following
      either diethylmaleate (DEM) or buthionine sulfoximine (BSO) treatment. Lipid
      peroxidation, assessed as thiobarbituric acid-reactive substances, was 40% lower
      in nkef-B-transfected cells compared with vector-only-transfected cells. DEM
      induced lipid peroxidation was suppressed by NKEF-B at DEM concentrations of 20
      microM to 1 mM. At 10 mM DEM, lipid peroxidation was unaffected by NKEF-B. NKEF-B
      expression also protected cells against menadione-induced inhibition of [3H]
      thymidine uptake. The NKEF-B protein appears most effective in suppressing basal
      low-level oxidative injury such as that produced during normal metabolism. These
      results indicate that overexpression of the NKEF-B protein promotes resistance to
      oxidative stress in this endothelial cell line.

PMID- 9161850
TI  - An investigation of the antioxidant activity of black tea using enhanced
      chemiluminescence.
AB  - Antioxidants are important species which possess the ability to protect the body
      from damage caused by free radical-induced oxidative stress. A variety of free
      radical-scavenging antioxidants exist within the body many of which are derived
      from dietary sources. There is currently much interest in the antioxidant role of
      flavonoids and other polyphenols found in tea, wine, fruit and vegetables.
      Enhanced chemiluminescence is a simple technique which can be used as a rapid and
      sensitive assay for measuring the antioxidant activity of beverages such as green
      and black tea. This article examines the impact of water temperature, stewing
      time, leaf concentration and the addition of milk upon the antioxidant activity
      of black tea solutions. The antioxidant activity of a range of commercially
      available black and green teas has also been measured.

PMID- 9161851
TI  - [Clinical studies on renal pelvic and ureteral carcinoma].
AB  - We reviewed 40 patients with renal pelvic and/or ureteral transitional cell
      carcinomas, consisting of 24 males and 16 females with a mean age of 65 years.
      The histopathological stage of surgically removed specimen was pTa in 6 patients,
      pT1 in 7, pT2 in 5, pT3 in 11 and pT4 in 6. Three patients with Tis and 2 with T3
      did not undergo surgery. Of 35 patients pathologically examined, lymphatic and
      venous invasions were detected in 22 (63%) and 16 (46%), respectively, and were
      associated with pathological stage and grade. Overall the 5-year actuarial
      survival rate was 57.1%. Tumor staging and vascular invasion had a prognostic
      significance on the treatment outcome, but not metachronous or synchronous
      bladder cancer, identified in 55% of the patients. Adjuvant chemotherapy appeared
      to improve the survival of the patients with tumors pT2 or higher, grade 3 or
      vascular invasion without metastases.

PMID- 9161852
TI  - [Long-term follow-up of female tetraplegic patients with cutaneous vesicostomy].
AB  - Tetraplegic women who underwent a cutaneous vesicostomy in our institutions were
      studied to evaluate long-term urinary complications and their quality of life
      (QOL). A total of 5 patients (C4, C5 and C6 injuries in one patient each and C7
      injury in 2) were followed for 98 to 125 months (mean 107 months). Autonomic
      hyperreflexia disappeared after surgery in all patients. None of the patients
      showed deterioration of the upper urinary tract. Urinary tract infections were
      noted in 3 of 5 patients, but not severe. Bladder stones developed in 2 patients
      and a stomal stricture in 1. A questionnaire survey showed the patients to be
      satisfied with the operation, which had improved their QOL. These findings
      suggest that a cutaneous vesicostomy is an excellent surgical procedure for
      tetraplegic women.

PMID- 9161853
TI  - [Urinary interleukin-6 and interleukin-8 in females with urethral syndrome].
AB  - Interleukin-6 (IL-6) and interleukin-8 (IL-8) are important mediators of an
      inflammatory response. We measured creatinine-collected urinary levels of IL-6
      and IL-8 by an enzyme-linked immunosorbent assay in 21 women with urethritis
      syndrome as well as 20 age-matched healthy women. Urine samples were collected
      before treatment and after 7 or 14 days of oral administration of sparfloxacin
      (100 mg once daily). Urinary IL-6 level was elevated in a patient with urethritis
      syndrome (41.1 pg/mgCr), while urinary IL-8 levels were elevated in 8 (range 13.3
      to 560 pg/mgCr). On the other hand, none of the healthy controls showed any
      detectable urinary level of IL-6 and IL-8. Of the 9 patients with elevated
      urinary IL-6 or IL-8, symptomatic improvement was obtained after chemotherapy in
      8 and urinary interleukins became undetectable in 7. Urinary IL-6 and IL-8 seem
      to have some role in the induction of urinary symptoms.

PMID- 9161854
TI  - [Effects of gosha-jinki-gan on urinary bladder contraction in dogs].
AB  - The effects of Gosha-Jinki-Gan on the urinary bladder contraction in anesthetized
      dogs were studied to elucidate the mode of action. The bladder contraction was
      induced by electrical stimulation of the left distal end of the pelvic nerve
      under the bilateral pelvic nerve and hypogastric nerve transections, or by the
      infusion of acetylcholine (200 micrograms) in to the abdominal aorta. The bladder
      contraction induced by pelvic nerve stimulation was significantly inhibited by 10
      and 100 mg/kg of intravenous Gosha-Jinki-Gan administration. A similar phenomenon
      was observed by the administration of atropine sulfate (0.1 mg). The
      acetylcholine-induced contraction was significantly inhibited by administration
      of 100 mg/kg of Gosha-Jinki-Gan. These findings suggested that Gosha-Jinki-Gan
      inhibits the urinary bladder contraction induced by the stimulation of
      cholinergic nerve.

PMID- 9161855
TI  - [A case of concurrent bilateral adrenocortical adenoma causing Cushing's
      syndrome].
AB  - A 43-year-old woman presented with obesity and lumbago. Endocrinological
      examinations revealed normal plasma cortisol levels and a suppressed serum
      adrenocorticotropic hormone (ACTH) level. On venous sampling, markedly elevated
      plasma cortisol levels were observed for bilateral adrenal veins (243 and 62.3
      micrograms/dl on the right and left sides, respectively). Although the computed
      tomogram revealed bilaterally enlarged adrenal glands, 131I-adosterol scintigram
      showed a strong uptake only on the right side. Right adrenalectomy successfully
      relieved Cushing's syndrome. Pathological diagnosis was adrenocortical adenoma,
      3.5 cm in diameter. Cushing's syndrome recurred in 9 years. At that time, she
      underwent left subtotal adrenalectomy including a 3-cm adrenocortical adenoma.
      Postoperative convalescence has been uneventful with oral steroid
      supplementation. All 14 previously reported cases of bilateral adrenocortical
      adenoma (BAA) causing Cushing's syndrome as well as the present case were
      concurrent and dominant in females of reproductive age. This suggests that some
      cofactors other than ACTH, such as estrogen, contribute to the pathogenesis of
      BAA.

PMID- 9161856
TI  - [Renal cell carcinoma in a horseshoe kidney: a case report].
AB  - A 69-year-old man presented for further examination for left renal mass. Computed
      tomography and magnetic resonance imaging revealed a heterogenous mass on the
      left side of a horseshoe kidney accompanied with renal vein thrombus. Aortography
      showed a hypervascular mass in the left kidney and aberrant arteries to the
      isthmus originating from the aorta. A left nephrectomy with the division of the
      isthmus was performed through an abdominal transperitoneal approach. Histological
      evaluation revealed grade 2, stage T3b, renal cell carcinoma. The patient was
      free of tumor, but died of intracerebral hemorrhage 5 months after the operation.

PMID- 9161857
TI  - [A case of renal cell carcinoma associated with ossification].
AB  - A 40-year-old woman presented with left lumbar pain. A plain abdominal
      roentgenogram showed patchy calcifications dispersed in a diameter of 7.5 cm at
      the lower pole of the left kidney. Computed tomography and angiography revealed a
      hypovascular tumor 10 cm in diameter. A left radical nephrectomy was performed.
      Histopathological diagnosis was renal cell carcinoma, clear cell subtype,
      pT2N0M0, accompanied with marked stromal calcification. The patient remains free
      of recurrence 42 months postoperatively. This is the 26th case reported in the
      Japanese literature.

PMID- 9161858
TI  - [Renal cell carcinoma in acquired cystic disease of kidney (ACDK) manifested by
      spontaneous renal rupture: a case report].
AB  - We report a case of renal cell carcinoma in acquired cystic disease of the kidney
      (ACDK) presenting with a spontaneous renal rupture. A 41-year-old man on chronic
      hemodialysis for 16 years was referred to our hospital with sudden left back
      pain. On arrival, the patient was in a state of hemorrhagic shock but his general
      condition improved by conservative therapy. Computed tomography demonstrated a
      left renal rupture as well as bilateral ACDK. Although there was no definite
      evidence of a renal tumor, a left radical nephrectomy was performed one week
      later. The resected kidney contained a yellowish-brown tumor of 5.5 x 5.0 x 4.5
      cm in size. Pathological examination revealed renal cell carcinoma, cystic type,
      clear cell subtype, pT2pN0M0. He has been free of recurrence for 3 months.

PMID- 9161860
TI  - [Spontaneous urinary extravasation from the renal pelvis associated with ureteral
      fibroepithelial polyp: report of a case].
AB  - A 26-year-old woman presented with a colicky right flank pain. Retrograde
      pyelogram showed extravasation of the contrast medium from the right renal pelvis
      and a filling defect in the right ureter 4.5 cm proximal to the ureteral orifice.
      Urinary cytology was negative for malignancy. A partial ureterectomy with a
      vesicoureteroneostomy was performed. Gross inspection of the resected distal
      ureter revealed a 3-mm polyp with a grayish-white smooth surface as well as a
      ureteral stenosis of 2 cm in length just distal to the polyp. Pathological
      diagnosis was a fibroepithelial polyp. In our case, urinary extravasation
      probably resulted from an impacted polyp in the stenotic ureter.

PMID- 9161859
TI  - [Bellini duct carcinoma of kidney with invasive growth pattern: a case report].
AB  - We report a case of Bellini duct carcinoma of the left kidney with invasive
      growth pattern. A 39-year-old man was admitted to our hospital with the chief
      complaint of gross hematuria. Ultrasonography showed left renal swelling but
      normal reniform configuration of the kidney was maintained. Computed tomography
      demonstrated a low density tumor infiltrating into the renal cortex and with
      tumor extension into the renal vein. Renal angiography revealed a hypovascular
      tumor. We suspected a left renal cell carcinoma with tumor extension into the
      left renal vein, and performed radical nephrectomy. Macroscopically, the resected
      kidney had a normal outer contour. The tumor with infiltrative growth pattern
      existed in renal medulla. Histopathologic examination revealed a papillary
      adenocarcinoma originated in Bellini duct (pT3bN2M0). The patient underwent
      systemic chemotherapy (M-VAC). This case showed invasive growth pattern, which
      were different from the usual renal cell carcinoma and Bellini duct carcinoma.

PMID- 9161861
TI  - [A case of uretero-aortic fistula].
AB  - We report a case of uretero-aortic fistula. A 69-year-old man with rectal cancer
      underwent a pelvic exenteration and a double--barreled cutaneous ureterostomy in
      the right lower abdomen. Stomal stenosis necessitated continuous indwelling of
      double J stents in the two ureters. Two years postoperatively, massive bleeding
      occurred during exchange of double J catheters. Occlusive ureterogram
      demonstrated a uretero-aortic fistula at the crosspoint between the left ureter
      and the aorta. The surgical repair consisted of closure of the aortic fistula,
      ligation of the left ureter proximal to the fistula and percutaneous left
      nephrostomy.

PMID- 9161862
TI  - [Primary carcinoma of the female urethra: report of five cases].
AB  - Between 1988 and 1996, we treated five patients with primary carcinoma of the
      female urethra between 65 and 79 years of age. Presenting symptoms included a
      urethral mass in 2 patients, hematuria in 1, dysuria in 1 and urethral bleeding
      in 1. Histopathology revealed squamous cell carcinoma in 4 cases and transitional
      cell carcinoma in 1. Clinical stage according to Grabstald's classification
      comprised Stage A in two cases, Stages B, C and D in one each. The modes of
      treatment were surgical resection alone in two, radiation therapy alone in two,
      and surgery with adjuvant chemotherapy in one case. Three patients without
      disease and two with disease are olive from 5 to 87 months after diagnosis.

PMID- 9161863
TI  - [Hemo-lymphangioma of the scrotum: a case report].
AB  - A 3-year-old boy was referred because of a painless mass in the left scrotum. On
      palpation, the mass was discriminated from the testis, epididymis and spermatic
      cord and showed transillumination. A part of the mass was dark purple in color.
      Total surgical excision of the mass was performed. The lesion was multicystic (2
      15 mm), adherent to the scrotal skin, and easily dissectable from the testicle.
      Pathological examination revealed lymphangioma as a major component and
      hemangioma as a minor part. He has been free of recurrent disease for 2 years.
      This is the 7th case of hemo-lymphangioma of the scrotum in the Japanese
      literature.

PMID- 9161864
TI  - [Effect of Chorei-to on spontaneous discharge of urinary stones after
      extracorporeal shock wave lithotripsy (ESWL)].
AB  - To enhance stone elimination following extracorporeal shock wave lithotripsy
      (ESWL), we administered Tsumura Chorei-to to 74 patients who underwent the
      procedure at Kinki University School of Medicine and Kanbara Hospital between
      July 1990 and March 1991. We established a control group of 75 patients without
      medication. There was no significant difference between the two groups in terms
      of gender, age, stone size (mostly less than 20 mm), and stone position. The mean
      number of days required for complete stone elimination was 16.0 days in the
      Chorei-to administration group being significantly shorter than the 21.5 days in
      the control group (p < 0.001). These findings suggested that Chorei-to
      effectively enhanced the spontaneous discharge of fragmented stones following
      ESWL.

PMID- 9161865
TI  - The measurement of neonates.
AB  - Accurate measurements of both healthy and premature neonates are possible but
      rarely performed. Routine anthropometry is often not performed at all or with
      large measurement errors due to inadequate training of personnel or inappropriate
      equipment. Sick neonates are often considered unsuitable for anthropometry and
      growth is wrongly equated with weight gain. Gain in length may be disturbed by
      poor health and permanent extrauterine growth retardation and changes in body
      proportions induced in some survivors of neonatal intensive care. Drug treatments
      may have profound effects on length gain and the relationship of length to
      weight.

PMID- 9161867
TI  - The timing of early postnatal catch-up growth in normal, full-term infants born
      short for gestational age.
AB  - Postnatal catch-up growth in infants born small for gestational age has been
      reported to occur mainly during the initial 3-9 months of life. The study
      presented here characterized early postnatal growth in healthy, full-term infants
      born short for gestational age (GA) (< -2 standard deviation scores [SDS] in
      birth length) in two populations. Results from a longitudinal growth study from
      birth to final height of 139 infants born short for GA between 1973 and 1975 in
      Goteborg, Sweden, were compared with results from an ongoing detailed prospective
      6-month follow-up of 41 Hong Kong Chinese infants born short for GA in 1995 and
      1996. For both populations, height was expressed in SDS using the updated Swedish
      growth reference data at birth and postnatally. In the Swedish study, 92% of the
      children born short for GA reached a final height greater than -2 SDS; 76% had a
      height greater than -2 SDS by 2 months of age. In the Hong Kong study, 79%
      reached a height greater than -2 SDS by 5 months of age (the longest follow-up
      time to date). A third population of Hong Kong Chinese infants born short for GA
      in 1967 was studied; 65% had reached the normal height range by 5 months of age.
      In the later Hong Kong study (1995-1996), catch-up growth could be identified as
      early as 12 weeks of age, which has important implications for clinical practice.
      Thus, growth monitoring during the first weeks of postnatal life gives useful
      information on catch-up growth in infants born short for GA.

PMID- 9161866
TI  - The physiology and pathophysiology of intrauterine growth retardation.
AB  - Insulin-like growth factor I (IGF-I) is the primary hormone influencing fetal
      growth in later gestation. The regulation of fetal IGF-I in utero is primarily
      influenced by placental glucose transfer, which regulates fetal insulin release.
      Furthermore, insulin has direct adipogenic effects on the fetus; fetal growth
      hormone (GH) may also have additional modes of action on fetal growth. Swallowed
      amniotic fluid contains IGF-I and may influence gastrointestinal maturation and
      fetal growth. Furthermore, both fetal and maternal IGF-I can influence placental
      metabolism. Experimentally, the maternal administration of GH and IGF-I can
      affect placental function and thus influence fetal growth; this may suggest
      therapeutic approaches to the treatment of intrauterine growth retardation (IUGR)
      in utero. Both experimental and clinical evidence support our hypothesis that
      IUGR is a multihormone relative resistance syndrome; relative resistance to
      insulin, IGF-I and GH can be demonstrated. Such resistance may be the basis of
      altered programming by which fetal growth retardation is associated with
      postnatal growth failure and a greater propensity to develop cardiovascular and
      metabolic disease in later life.

PMID- 9161868
TI  - Prenatal factors influencing long-term outcome.
AB  - Animal studies have shown that undernutrition before birth programmes persisting
      changes in a range of metabolic, physiological and structural parameters. Studies
      in humans have shown that men and women who had birth weights at the lower end of
      the normal range, who were thin or short at birth, or who were small in relation
      to placental size, have increased rates of coronary heart disease. This article
      suggests how fetal undernutrition at different stages of gestation may be linked
      to these patterns of early growth. Adaptations by the fetus to undernutrition are
      associated with changes in the concentrations of fetal placental hormones.
      Persisting changes in the level of hormone secretion and tissue sensitivity may
      link fetal undernutrition with adult disease.

PMID- 9161869
TI  - Puberty in children with intrauterine growth retardation.
AB  - There is a remarkable scarcity of data concerning puberty in children born with
      intrauterine growth retardation (IUGR). What little there is suggests that
      puberty occurs at a normal age compared with the general population, but a little
      early compared with other short children. The pattern of puberty is quite normal
      in children born with IUGR, with normal inter-relationships between the various
      events, although the growth spurt is, on average, a little less intense than in
      the normal population. In general, adult height is significantly compromised,
      partly because of the rather attenuated pubertal growth spurt.

PMID- 9161870
TI  - Anthropometry and body composition in children.
AB  - Changes in body fat, fat-free mass and extracellular water occur in many
      disorders, and during normal growth in children. Thus, body composition is an
      increasingly important measurement in paediatric clinical practice, and is used
      for diagnostic purposes, for decisions for treatment and for monitoring
      improvement. A number of different methods exist for determining body composition
      in children; however, their use is complicated by the absence of a gold standard
      and the lack of validity data in children both with and without growth disorders.
      In this report, validity and usefulness are compared among anthropometric methods
      and weighted against other techniques used in children. Recent recommendations of
      a number of expert committees are discussed.

PMID- 9161871
TI  - Dual-energy X-ray absorptiometry in early life.
AB  - Dual-energy X-ray absorptiometry (DXA) is a safe and quick technique, and
      requires little cooperation from the patient. DXA has therefore been introduced
      progressively in paediatrics and neonatology to study bone mineral content and
      body composition. The limits of DXA are related mainly to accuracy, and it is too
      early to claim that DXA is a 'gold standard' technique for body composition
      research. However, DXA appears to be an adequate tool for measuring bone mass and
      body composition in the clinical setting, and it represents the best technical
      choice for paediatric use to date.

PMID- 9161872
TI  - Stable isotopes and bioelectrical impedance for measuring body composition in
      infants born small for gestational age.
AB  - The assessment of body composition in infants born small for gestational age
      (SGA) is required primarily to evaluate nutritional status and to monitor growth
      in the neonatal period. Measurement of total body water, using stable isotopes of
      hydrogen (2H) and oxygen (18O), offers a potential method by which body
      composition can be assessed. This technique is non-invasive and recently has been
      used successfully in a cohort of 5-week-old infants born SGA. Nevertheless, the
      assessment of total body water using stable isotopes requires specialized
      laboratories and equipment, which may limit its use. Prediction of total body
      water by bioelectrical impedance is a possible alternative. This technique uses
      electrical theory to predict the volume of the conducting medium in the body,
      namely, water. A potential limitation of bioelectrical impedance analysis is the
      accuracy, which may impinge on its usefulness in small infants.

PMID- 9161874
TI  - Persistent short stature in children with intrauterine growth retardation: use of
      growth hormone treatment.
AB  - Since the early 1970s, it has been demonstrated that growth hormone (GH)
      treatment improves the short-term growth rate of children with short stature due
      to intrauterine growth retardation (IUGR). However, it is only in recent years
      that studies have been conducted in which children with IUGR have been followed
      to final height. It is appreciated that pharmacological doses of GH are required
      for the treatment of short children with IUGR, and that the initial effect of
      rapid advancement of epiphyseal maturation is probably due more to the natural
      history of growth in children with IUGR than to the GH treatment. Initial studies
      are promising, showing that the rapid improvement in growth rate is eventually
      translated into an improvement in final height. However, studies involving a
      larger number of children with IUGR are necessary in order to quantify this
      improvement in final height.

PMID- 9161873
TI  - Measurement of body composition: applications in hormone research.
AB  - Measurements of body composition are fundamental to the diagnosis and management
      of a number of diseases. However, these measurements must be appropriate and
      accurate. Accuracy can now be achieved, but at the expense of invasiveness
      (mainly radiation) and cost. Some methods for measuring body composition, such as
      bioimpedance analysis, are inexpensive, simple, harmless and infinitely
      repeatable. The remaining methods fall within a scale of increasing
      discriminating power and increasing cost/risk/difficulty. In this review, a
      number of methods of measuring body composition are discussed. Both traditional
      and new methods are included, which vary in ease of use, invasiveness and cost.
      The choice of technique depends on the needs of a particular study.

PMID- 9161875
TI  - Growth hormone treatment induces a dose-dependent catch-up growth in short
      children born small for gestational age: a summary of four clinical trials.
AB  - In the present study, data from 230 short children born small for gestational
      age, who were participating in four clinical trials, were pooled and analysed. At
      the start of GH treatment, median age and height SDS were 5.3 years and -3.2 SDS,
      respectively. A dose-dependent increase in height SDS was observed following 2
      years of GH treatment: 1.1, 1.7 and 2.5 SDS for the three GH treatment groups
      (0.1, 0.2 and 0.3 IU/kg/day, respectively), compared with an increase of 0.14 SDS
      in the control group. In a multiple regression analysis, four variables were
      found to correlate independently with the gain in height SDS following 2 years of
      GH treatment. These are given below in order of importance: gain in height SDS =
      7.7 x dose of GH (IU/kg/day) -0.11 x age (years) -0.08 x parental-adjusted height
      SDS + 0.05 x birth length SDS (SD = 0.5; r2 = 0.64). At the end of the 2-year
      study period, a total of 48%, 66% and 90% of patients in the groups given GH at
      0.1, 0.2 and 0.3 IU/kg/day, respectively, had a parental-adjusted height greater
      than -1.0 SDS.

PMID- 9161876
TI  - Growth hormone treatment in short children born small for gestational age: from
      controversy towards consensus.

PMID- 9161877
TI  - Chlorpromazine inhibits concanavalin A-induced liver injury independently of
      cytokine modulation.
AB  - We investigated the effect of chlorpromazine (CPZ) in a murine model of T-cell
      dependent liver injury caused by concanavalin A (ConA). CPZ (3 and 10 mg/kg)
      treatment 1 h before ConA injection prevented liver injury. CPZ (3, 10 mg/kg)
      administered 1 h after a ConA injection was also hepatoprotective, whereas
      cyclosporin (CsA, 100 mg/kg) was active only when given before ConA. Under either
      condition, CsA but not CPZ prevented concurrent increases in splenic ornithine
      decarboxylase (ODC) activity, a putative index of T-cell
      proliferation/differentiation. CPZ down-regulated tumor necrosis factor-alpha
      (TNF-alpha) and up-regulated IL-10 in mice that then received ConA, whereas
      delayed administration of CPZ had no effect. These results suggest that CPZ
      prevented liver injury without affecting the proliferation/differentiation of T
      cells. The dissociation of hepatoprotection by CPZ from cytokine modulation
      indicates that this drug intervenes in the adherence of T-cells or the death of
      hepatocytes in the ConA-model.

PMID- 9161878
TI  - The effect of immunomodulation of stimulator antigen presenting cells on
      subsequent responder T-cell function.
AB  - In this study, we examined whether lipopolysaccharide (LPS)-, interferon-gamma
      (IFN-gamma) or 16,16-dimethyl prostaglandin E2 (dmPGE2)-pretreatment of
      stimulator spleen cells from C57BL6 (B6) mice affects effector function of
      responder T-lymphocyte from C3H/HeJ mice. Stimulation of B6-derived splenic
      mononuclear cells (SMNCs) with LPS (10 micrograms/ml) prior to their utilization
      as stimulator cells in a mixed lymphocyte culture (MLC) resulted in an increase
      in responder T-lymphocyte proliferation compared to utilization of unstimulated
      SMNC (P < 0.05). IFN-gamma demonstrated similar effects in a dose dependent
      fashion with maximal stimulatory effect seen at 1000 U/ml. In contrast,
      pretreatment of stimulator SMNC with dmPGE2 resulted in dose-dependent inhibition
      of the responder T-lymphocyte proliferation with maximum inhibitory effect seen
      using a concentration of dmPGE2 of 10(-5) M. The presence of indomethacin in the
      MLC did not reverse this effect. These data demonstrate the effect of
      immunomodulation of stimulator spleen cells on subsequent T-lymphocyte function.

PMID- 9161879
TI  - Characterization of a series of vacuolar type H(+)-ATPase inhibitors on CTL
      mediated cytotoxicity.
AB  - Four vacuolar type H(+)-ATPase (V-ATPase) inhibitors, i.e. concanamycin A (CMA),
      bafilomycin A1 (BMA), destruxin E (DRE) and prodigiosin 25-C (PRG) profoundly
      blocked the perforin-dependent cytotoxicity mediated by CD8+ CTL clone.
      Cytoplasmic acidic compartments were not detected under fluorescent microscopy
      after treatment of the cells with these V-ATPase inhibitors. In the lytic granule
      fractions, BMA, CMA, DRE and PRG completely abrogated the perforin activity,
      although these drugs slightly decreased the granzyme A activity. Under the same
      conditions, BMA and CMA markedly reduced the perforin content, while DRE and PRG
      had no significant effects as assayed by immunoblotting using anti-perforin
      antibody. These data suggest that perforin is predominantly inactivated even
      without proteolysis in DRE- or PRG-treated cells. We propose that acidic pH is
      essential to maintain not only quantity but also quality of perform in the lytic
      granules.

PMID- 9161880
TI  - Characterization of an HIV-1 p24gag epitope recognized by a CD8+ cytotoxic T-cell
      clone.
AB  - A CD8+ cytotoxic T-cell clone that recognized HIV p24gag was isolated from an
      infected individual. The minimal epitope was localized to amino acids 308-316
      (QASQEVKNW). Using allogeneic target cells, we found that lysis was restricted by
      the HLA-Cw0401 molecule. We observed that C1R cells, that express the HLA-Cw0401
      allele are able to present the peptide to the cytotoxic clone, but with reduced
      efficiency. Other B-cell lines, that have been genotyped as HLA-Cw0401+ were
      unable to present the peptide to the clone, suggesting the existence of other
      variants of HLA-Cw0401 or a loss of cell surface expression of this molecule.

PMID- 9161881
TI  - Identification of lymphocyte 5-HT3 receptor subtype and its implication in fish T
      cell proliferation.
AB  - In the present study, we identified the serotonergic receptor of type 3 (5-HT3)
      on the lymphocytes of a teleost fish, Oncorhynchus mykiss. In the pharmacological
      studies on the binding of [3H]serotonin to membrane receptor sites, 2-methyl-5
      HT, an agonist of 5-HT3 receptors, displaced the binding of [3H]serotonin to fish
      lymphocytes, indicating the presence of 5-HT3 receptors on these cells. The known
      antagonists of the mammalian 5-HT3 receptor, ICS-205-930 and metoclopramide,
      failed to displace [3H]serotonin binding to lymphocytes during the period of
      association equilibrium (8 min); however, these antagonists progressively
      displaced [3H]serotonin binding from 10 to 40 min of incubation. These results
      suggest that fish 5-HT3 lymphocyte receptors may differ pharmacologically from
      mammalian receptors. As mammalian 5-HT3 receptors are coupled with Na+ inward
      movements, we undertook a study on Na+ influx by using SBFI/AM, a fluorescent
      probe. In SBFI/AM loaded fish lymphocytes, 2-methyl-5-HT leaked Na+ inward
      movements. Prior incubation of lymphocytes for 30 min in the presence of 5-HT3
      antagonists, ICS-205-930, metoclopramide and MDL-72222, curtailed significantly
      the Na+ influx evoked by 2-methyl-5-HT, demonstrating that Na+ is leaked into
      fish lymphocytes via the 5-HT3 receptor-channel whose functioning is blocked by
      these antagonists. Furthermore, 2-methyl-5-HT exerted immunosuppressive effects
      in a dose dependent manner on fish T-lymphocytes stimulated by
      phytohaemagglutinin (PHA). Serotonin and 2-methyl-5-HT blocked the cell cycle
      progression of PHA-stimulated T-cells from G0/G1 to S phase. The
      immunosuppressive effects of 2-methyl-5-HT on T-cells were partially reversed by
      the antagonists, metoclopramide and ICS-205-930; however, the latter antagonist
      at high concentrations synergized with the immunosuppressive effects of 2-methyl
      5-HT. These results demonstrate that the fish lymphocyte 5-HT3 receptor, which
      may be pharmacologically different from mammalian receptor subtype, is
      functionally implicated in fish T-cell proliferation.

PMID- 9161882
TI  - Interleukin-15 acts as an immunological co-adjuvant for liposomal antigen in
      vivo.
AB  - The recently discovered interleukin-15 (IL-15) is known to bind to the receptor
      of interleukin-2 (IL-2) and to share several of the latter's immunological
      properties. In the present study, the first to our knowledge on IL-15 behaviour
      in vivo, we examined the possibility that IL-15 also shares the ability of IL-2
      to enhance the immunological adjuvant property of liposomes by acting as a co
      adjuvant. The cytokine and a model antigen (tetanus toxoid) were either co
      entrapped by the dehydration rehydration method into, or covalently co-linked by
      diazotization to the surface of the same liposomes, or entrapped in different
      liposome populations. Intramuscular immunization of CD-1 mice with a variety of
      IL-15 and toxoid formulations revealed that IL-15 augments anti-toxoid IgG (IgG1,
      IgG2, IgG2b) responses well above (up to ten-fold) those achieved with liposomal
      toxoid alone (or with a mixture of free IL-15 and toxoid) when the cytokine and
      the antigen are associated with the same vesicles but not when in different
      vesicle populations that were mixed before injection. Higher responses were
      observed for all three subclasses studied only with liposomes where IL-15 and
      antigen were accommodated on their surface.

PMID- 9161883
TI  - Mechanism of interaction of pH 3.0 treated tumor cells expressing lower levels of
      class I MHC antigens, with IL-2 activated NK cells.
AB  - Effect of lowering the levels of class I MHC antigens, on the ability of three
      murine (YAC, P815, SP2O) and three human (Molt4, Raji, HR7) tumor cell lines, to
      compete in cold target inhibition assays, was studied. Specific reduction in
      class I MHC levels (range 60-76%) was induced by brief exposure to citrate buffer
      (pH 3.0). Susceptibility of the acid pH treated tumor cells to lysis by IL-2
      activated NK cells, was found to be significantly increased in all cases with the
      exception of YAC cells. Reduction in class I MHC antigen expression by acid pH
      treatment, had no significant effect on competing ability of the tumor cells. In
      contrast, tumor cells on which MHC class I antigens were upregulated by
      interferon treatment, had significantly lower ability to compete. These results
      suggest that the mechanisms of altered interactions between MHC I up or down
      regulated target cells may be different. A model compatible with increased NK
      susceptibility along with an unaltered ability to compete for acid pH treated
      tumor cells, has been proposed.

PMID- 9161884
TI  - Effect of TSH and anti-TSH receptor antibodies on the plasma membrane potential
      of polymorphonuclear granulocytes.
AB  - Effects of thyrotropin hormone (TSH) and anti-TSH receptor antibodies on the
      plasma membrane potential of polymorphonuclear granulocytes (PMN) were analyzed
      by means of flow cytometry. Both TSH and the autoantibody caused a rapid, dose
      dependent hyperpolarization of the plasma membrane of PMNs. TSH was also able to
      mask (revert) the depolarizing effect of a chemotactic peptide, fMLP, on PMNs. No
      detectable rise in the cytosolic free calcium level accompanied the observed
      hyperpolarization. Quinine, a blocker of Ca(2+)-activated and voltage-gated K+
      channels did not affect the hyperpolarization by TSH and antibodies. Decreasing
      the [K+] gradient across the plasma membrane by valinomycin, however, blocked the
      hyperpolarizing effect. Peptide362-376 (derived from the extracellular domain of
      TSH receptor) also blocked the hyperpolarization induced by both TSH and anti
      TSHR antibodies. These data suggest that the observed hyperpolarization is a
      specific, receptor-mediated early signal during interaction of PMNs with TSH or
      anti-TSHR antibodies.

PMID- 9161886
TI  - Autologous lymphoblastoid cell lines stably transfected with Plasmodium
      falciparum circumsporozoite protein as targets in cytotoxic T-lymphocyte assays.
AB  - To produce cell lines that can be used as a continuous source of antigen
      presenting cells for stimulating T-cell lines and clones and as targets in
      cytotoxic T-lymphocyte (CTL) assays, we used a retroviral vector with a simian
      virus (SV40) early promotor to transfer a Plasmodium falciparum circumporozoite
      (PfCSP) gene into human EBV transformed B-lymphoblastoid cell lines (B-LCL). We
      herein report successful, stable transfection and cell surface expression of this
      gene, as confirmed by PCR, Western blot analysis and immunoelectron microscopy.
      One of three successfully transfected autologous cell lines expressed PfCSP on
      the cell surface and was lysed by CD8+ T-cell dependent CTL from a donor
      volunteer who had been immunized with irradiated P. falciparum sporozoites. Such
      cell lines should provide excellent tools for characterizing human CD8+ T-cell
      responses against Plasmodium sp. proteins.

PMID- 9161885
TI  - The T-cell receptor associated zeta-chain is required but not sufficient for CD26
      (dipeptidylpeptidase IV) mediated signaling.
AB  - CD26 or dipeptidylpeptidase IV (DPP IV) is a cell surface protease involved in T
      cell activation. Triggering or costimulation of T-cells via CD26 was shown to be
      dependent on the expression of the T-cell receptor (TCR) associated zeta-chain
      with at least one functional immune receptor tyrosine based activation motif
      (ITAM). Here we tested T-cell lines expressing chimeric proteins (hCD25-zeta)
      consisting of human IL-2 receptor-alpha chain derived extracellular sequences
      (hCD25) fused to mouse-specific zeta-chain segments, for their capacity to
      transfer CD26 mediated signals. Although these 'minimal receptor' expressing T
      cell lines were capable of transmitting signals from other costimulatory
      molecules (e.g. CD2), crosslinking of CD26 did not induce IL-2 secretion. Co
      cross-linking of hCD25 and CD26 molecules, however, resulted in the stimulation
      of the T-cells. Thus, although the zeta-chain is a prerequisite for CD26 mediated
      signaling events, the sole expression of zeta-protein as a signaling molecule is
      not sufficient for CD26 mediated triggering but permits CD26 induced
      costimulation in TCR negative cells.

PMID- 9161887
TI  - Somatosensory event-related potential changes to painful stimuli during hypnotic
      analgesia: anterior cingulate cortex and anterior temporal cortex intracranial
      recordings.
AB  - The present study examined neurophysiological correlates of pain and pain control
      by recording intracranial somatosensory event-related potentials (SERPs) to
      painful cutaneous stimuli in two female patients with obsessive-compulsive
      disorder bearing multiple intracranial electrodes during conditions of (a)
      attention and (b) hypnotically suggested analgesia. Intracranial electrodes were
      located in the anterior cingulate cortex, amygdala, temporal cortex, and parietal
      cortex. No changes were observed in the SERPs of the hypnotically unresponsive
      patient. In the hypnotically responsive patient, reduced pain perception during
      suggested hypnotic analgesia was accompanied by (a) a significant reduction of
      the positive SERP component within the range of 140-160 ms post-stimulus in the
      left anterior cingulate cortex (Shaltenbrandt atlas: 29.12/ -7.42/32.41), and (b)
      a significant enhancement of the negative SERP component within the range of 200
      260 ms in the left anterior temporal cortex (Brodmann area 21). No significant
      changes were observed in the amygdala or the scalp-recorded Fz. The present study
      is the first to demonstrate the involvement of the anterior cingulate cortex and
      the anterior temporal cortex in the control of pain with hypnotically suggested
      analgesia.

PMID- 9161888
TI  - Effects of methylphenidate in children with attention deficit hyperactivity
      disorder: a comparison of event-related potentials between medication responders
      and non-responders.
AB  - Event-related potentials (ERPs) were compared among three groups, each with 13
      subjects: (1) ADHD non-responders to methylphenidate treatment; (2) ADHD
      responders to methylphenidate treatment; and (3) normal control children.
      Response to methylphenidate was determined through extensive psychoeducational
      and cognitive assessments during a 4-week double-blind medication assessment.
      ERPs were recorded each week from 13 active electrodes during a visual feature
      detection task and a semantic classification task. Significant group effects were
      found for N2 and P3b latencies due to longer latencies for the ADHD children. Off
      medication, there were no differences between responders and non-responders.
      However, on methylphenidate non-responders had significantly longer P3b latencies
      than responders. Cognitive testing also revealed differential performance on
      medication between non-responders and responders on the paired-associate learning
      (PAL) task. Thus, both cognitive and ERP measures were found to differentiate
      ADHD non-responders and responders to methylphenidate treatment.

PMID- 9161889
TI  - Topography of visually evoked brain activity during eye movements: lambda waves,
      saccadic suppression, and discrimination performance.
AB  - Eye movement-related brain activity was studied in 14 subjects by recording EEG
      topographically in 16 channels over the occipital brain areas. Potential fields
      obtained with or without the simultaneous presentation of a visual stimulus
      during the time course of horizontal saccades were compared. Without visual
      stimulation, eye movements were followed at a mean latency of about 65 ms by a
      lateralized occipital dominant component whose topography was determined by the
      direction of the saccade but whose latency was independent of the time course of
      the eye movements. This component was reminiscent of lambda waves, however, it
      could also be elicited in complete darkness. When stimuli were presented during
      saccades, component latencies increased significantly, and there were also
      topographic changes in the evoked potential fields. Negative centroids were
      located more anteriorly and positive ones more posteriorly on the scalp when
      compared to brain activity recorded with stable eye positions and visual
      stimulation. All subjects reported no suppression of visual stimuli when
      presented during saccades occurred. This was confirmed by testing the
      discrimination performance of an independent group of 27 subjects. Our data show
      that the execution of saccades elicits electrophysiological patterns of
      activation in the visual cortex even without visual input. The increase of
      component latency observed during saccades as well as topographical differences
      suggest that visual information is processed by different neuronal elements
      during saccadic eye movements.

PMID- 9161890
TI  - Magnetic fields from human prefrontal cortex differ during two recognition tasks.
AB  - The present study represents our second successful use of magnetoencephalography
      to identify different sources of human prefrontal activity corresponding to
      subjects' engagement in different tasks. We used two visual recognition tasks: a
      familiar person recognition and an abstract pattern recognition task in the
      context of a design suitable for eliciting Contingent Negative Variations (CNVs)
      and their concurrent slow magnetic fields in this preliminary study of 5
      subjects. Each trial of either task was started by one of two specific warning
      symbols (S1), indicating whether a person's picture or an abstract pattern should
      be attended during the presentation of a second stimulus (S2), and compared to
      the corresponding person's picture or pattern contained in the third stimulus,
      (S3) that followed. The S2 and S3 stimuli were common to both tasks, and were
      composed of patterns made with four line traces superimposed on photographs of
      persons familiar to each subject. Subjects responded with a right hand button
      press, following S3, indicating their judgments regarding the identity of the
      patterns or persons' pictures contained in the S2 and the S3 stimuli, for the two
      tasks, respectively. Results showed that the sources of the CNV equivalent
      magnetic fields were localized in different cortical regions depending on the
      task and that this difference was consistent across all subjects. The sources
      were localized in the right hemisphere, in medial areas of the prefrontal cortex
      for the person recognition task and in the dorsolateral prefrontal cortex for the
      pattern recognition task. The same degree of consistency was not found for the
      left hemisphere sources. Moreover, as in our previous study, we found no
      difference between the sources active during the first and the second CNV periods
      (occurring during the S1-S2 and the S2-S3 intervals, respectively), within each
      task condition.

PMID- 9161891
TI  - The string measure of the ERP: what does it measure?
AB  - The event-related brain potential (ERP) has been investigated extensively inan
      effort to understand the neurophysiological bases of intelligence. Measures
      derived from the ERP have been used as indices of intelligence, particularly the
      string measure of the complexity of the ERP. However, the string measure has been
      criticised for being non-specific and for being dependent on ERP amplitude. These
      criticisms were tested by investigating relationships between ERP string measure,
      ERP amplitude measures, and the ERP power spectrum. It was found that the string
      measure was non-specific in that it indexes both low and high frequency event
      related activity; the string measure is also dependent on ERP amplitude. The
      string measure is therefore not a valid measure of the ERP. It was concluded that
      the string measure should be abandoned; human intelligence cannot map in a simple
      way onto gross measures of scalp-recorded electrocortical activity.

PMID- 9161892
TI  - Visual evoked potentials, heart rate responses and memory to emotional pictorial
      stimuli.
AB  - Although the effects of emotional stimuli on event-related cortical potentials,
      heart rate, and memory have been extensively studied, the association of these
      variables in a single study has been neglected. The influence of pleasant,
      unpleasant, and neutral photographic slides on visual evoked potentials (VEPs),
      heart rate responses, and free recall, was investigated in 20 normal subjects.
      VEPs were recorded from Cz and Pz locations, and analyses were performed on both
      amplitudes and latencies of identifiable endogenous peaks (P2, N2 and P3), and
      mean amplitude in the 100-200-ms, 400-600-ms, and 600-900-ms latency ranges. An
      emotional effect was present on VEPs starting from about 282 ms on, as revealed
      by the N2, P3, and late components. Both pleasant and unpleasant slides yielded
      larger cortical positivity as compared to neutral ones. Peak latencies did not
      show any emotional effect. Heart rate data showed a deceleratory response that
      was larger to unpleasant slides. Free recall of the projected slides showed a
      better performance for emotional slides compared to neutral ones. VEPs and memory
      data showed the same pattern: both pleasant and unpleasant slides induced larger
      positivity in the event-related potentials and were better remembered than
      neutral slides. Positive correlations were found between the late negative VEPs
      component (600-900 ms), recorded from Cz, and heart rate deceleration (r = 0.62),
      and between P3 (at Pz location) and the number of remembered slides (r = 0.53).

PMID- 9161893
TI  - Event-related potentials in parkinsonian patients under auditory discrimination
      tasks.
AB  - Seventeen non-demented idiopathic medicated Parkinsonian patients and 17 age- and
      education-matched controls participated in auditory discrimination tasks. The
      study aimed at revealing the differences in their ability for auditory
      information processing. Series comprising 1000 Hz and 800 Hz tones were used as
      stimuli. The accuracy in the tones' discrimination was determined by means of
      counting the high tone or recording a binary sensomotor reaction. The results
      based on the mean group values of event-related potential components show that
      the Parkinsonian patients had lower amplitude for the exogenous N1 and endogenous
      P3 components of the evoked responses. In the sensomotor task series the patients
      had longer N2 latency than controls. In the counting series the patients
      recognized the tones well and gave an exact count but during the sensomotor task
      they had longer reaction time, more erroneous answers and depressed P3. The data
      show differences in the information processing between the two groups and reveal
      cognitive impairment in the Parkinsonian patients.

PMID- 9161894
TI  - Historical aspects of cardiopulmonary bypass: from antiquity to acceptance.
AB  - Cardiopulmonary bypass has evolved from an extremely risky procedure into a safe
      systematic process, and is practiced daily in thousands of centers throughout the
      world. Numerous individuals, from diverse specialities, have contributed to the
      knowledge of the processes of extracorporeal flow. The developmental sequence of
      advances in cardiopulmonary bypass has been divided into three nonexclusive
      periods based on the major changes observed during the time: (1) a conceptual and
      developmental period, consisting of events that occurred before 1950; (2) an
      applied technological period, 1950 to 1970; and (3) a refinement period, 1970 to
      present. Within each time frame, the major findings regarding biological and
      technical challenges, extracorporeal device development, and applied clinical
      practice will be explored. Technological advances in cardiopulmonary bypass have
      permitted surgeons to treat patients with both congenital and acquired heart
      disease, and anesthesiologists to identify appropriate mixtures of treatment
      regimens, whereby the risks associated with managing this challenging patient
      population could be minimized.

PMID- 9161895
TI  - Oxygenator anatomy and function.
AB  - The natural lung is the organ responsible for oxygen and carbon dioxide exchange
      between the blood and the outside environment. This function is accomplished by
      the large surface area and high permeability of the gas exchange interface, the
      alveolar-capillary membrane. These same features are fundamental to the design of
      an artificial lung, or oxygenator. Additional lung-like features essential to the
      design of an ideal oxygenator include the ability to achieve balanced oxygen and
      carbon dioxide exchange with minimal blood damage and blood activation. The
      purpose of this review is to present the past and current developments of the
      oxygenator designs in terms of the structural and functional features of the
      natural lung as well as the limitations in the ability to mimic the features of
      the lung because of the lack of appropriate technology.

PMID- 9161896
TI  - Acid-base regulation, alpha-stat, and the emperor's new clothes.
AB  - Considerable time and effort have been expended to determine the most appropriate
      technique for management of a patient's acid-base status during hypothermic
      cardiopulmonary bypass. A critical question is whether to maintain plasma pH at
      7.4 regardless of temperature (pH-stat) or to permit a relative alkalosis as the
      patient is cooled (alpha-stat). Until recently, there has been a remarkable lack
      of evidence in the literature for a consistent physiological benefit provided by
      one protocol over the other. The alpha-stat versus pH-stat controversy has taken
      on the characteristics of the emperor's new clothes, with alpha-stat winning by
      default because of theoretical arguments and because it was technically easier to
      perform. Part of the explanation is the realization that cellular mechanisms are
      capable of maintaining intracellular pH despite fluctuations in extracellular
      conditions. The prevailing plasma pH does have strong influence over cerebral
      blood flow, even to the point of overriding normal autoregulatory mechanisms.
      Recent evidence suggests that cerebral blood flow variations between alpha-stat
      and pH-stat conditions have important implications for patient outcomes.

PMID- 9161897
TI  - Cardiac mechanical energy and effects on the arterial tree.
AB  - Blood flow pulsatility is the result of the heart's activity as a pump unable to
      develop steady flow, and its interaction with the arterial tree. Thus, the heart
      is a cyclic energy generator whose adequate function requires the two phases of
      this cycle to be normal. Diastolic properties determine the degree of filling of
      the ventricles and the strength of the following systole. Systole, in turn, must
      generate enough energy to overcome forces opposing ejection. These can be divided
      into internal (the mechanical characteristics of the ventricle itself) and
      external loads (the characteristics of the arterial tree). As a result, hydraulic
      energy is imparted to blood (external ventricular work) that manifests itself as
      blood pressure and flow. Given the cyclic nature of cardiac activity, the
      external ventricular work has steady and pulsatile components. The steady
      component is energy lost during steady flow because of vascular resistance, and
      the pulsatile work is that lost in arterial pulsations and mainly depends on the
      aortic impedance. Thus, the characteristics of the arterial tree will determine
      the relative contribution of these two components to blood flow and the efficency
      of the heart. In addition, the arterial tree modifies the different waves
      (pressure and flow) traveling in the circulation. These modifications have
      important consequences for cardiac function. The ventricle and the arterial tree
      constitute a coupled biological system, and its overall performance is a function
      of the behavior of each unit at any given moment.

PMID- 9161898
TI  - Mechanical simulation of cardiac function by means of pulsatile blood pumps.
AB  - After a review of the theoretical and experimental background, a history of the
      development of pulsatile blood pumps is presented with an attempt to understand
      the underlying rationale. The case for the use of pumps that simulate normal
      cardiac function is made by considering cardiovascular hemodynamics, the function
      of arterial baro-receptors, hemodynamic energy and power, tissue fluid movement,
      and lymph formation and flow. The pulsatile output of the heart and mechanical
      pumps is described in units of power and the load that they work against as a
      complex impedance. Many pulsatile pumps have been designed and developed for
      research, but few have been used during cardiac operations on human patients. The
      evidence in favor of using pulsatile flow for cardiopulmonary bypass is strong,
      but major problems have been identified such as the lack of a satisfactory
      definition of pulsatile flow and technical difficulties resulting from impedance
      mismatches in clinical applications.

PMID- 9161899
TI  - Pulsatile and nonpulsatile perfusion: the continuing controversy.
AB  - This report discusses pulsatile and nonpulsatile perfusion with regard to
      hemodynamics, cell metabolism, and the visceral consequences of these forms of
      cardiopulmonary bypass. It argues that differences between the two modes and a
      benefit for pulsatile perfusion, are most clearly manifested in identifiable high
      risk patient groups.

PMID- 9161900
TI  - The role of the vascular endothelium in inflammatory syndromes, atherogenesis,
      and the propagation of disease.
AB  - The vascular endothelium is intimately involved in a wide variety of normal
      physiological processes, including coagulation/anticoagulation, the maintenance
      of vascular tone, and pathological processes, including reperfusion injury,
      inflammatory syndromes, and tumor cell metastasis. This review discusses the
      importance of increased adhesive molecule expression on the endothelial surface
      in promoting circulating inflammatory cell-endothelial adherence in inflammatory
      conditions, as well as the role of the vascular endothelium in reperfusion
      injury, altered microvascular permeability states, and atherogenesis.

PMID- 9161901
TI  - The role of the pulmonary circulation in the regulation of coagulation and
      fibrinolysis in relation to major surgery.
AB  - Cardiac surgery and hip replacement surgery (HRS) are associated with serious
      cardiorespiratory and vascular complications. Activation of blood coagulation and
      fibrinolysis in the lung vasculature seem to play a key role in the
      pathophysiology of this process. This article reviews the results of several
      experimental and clinical studies within this field. Animal studies have shown
      that bone traumatization induces a marked local activation of coagulation and
      fibrinolysis in femoral vein blood draining from the surgical area as shown by a
      2.5-fold increase in plasma levels of thrombin-antithrombin complexes (TAT) and a
      seven-fold increase in tissue plasminogen activator (tPA) activity. A slight
      increase in TAT in femoral vein blood on the unoperated side has also been found
      and indicates increased activation of coagulation in recirculated blood, which
      had passed the pulmonary microvasculature. In addition, human studies have shown
      that bone preparation induced a 200-fold increase in systemic circulating
      fibrinopeptide-A during surgery and a five-fold increase in TAT (when
      thromboprophylaxis was stopped 1 week after surgery). Both increases are markers
      of thrombin generation. Furthermore, cellular studies have shown that thrombin
      and certain cytotoxic chemicals, such as methylmethacrylate monomer (bone
      cement), separately and together trigger monocytes to tissue factor (TF)
      expression and cause endothelial cell shape changes and detachment. This may
      allow pericellular fibrin formation to occur on monocytes and also transforms the
      nonthrombogenic endothelial coverage into a highly thrombogenic surface that
      triggers the conversion of fibrinogen to fibrin and releases fibrinopeptide-A.
      Finally, sequestration of granulocytes caused release of autodigestive proteases,
      which may have further strengthened this procoagulant process. Synchronous to the
      massive intrapulmonary activation of coagulation, an increased fibrinolytic
      activity was found, as evidenced by a marked drop in arterial blood tPA during
      surgery. This indicated tPA binding to fibrin deposits in the lung capillaries.
      However, this clearing process, to obtain adequate blood flow and gas exchange,
      was shut down several hours after surgery by an antifibrinolytic activity (PAI
      1). Thus, these studies indicated that bone surgery induces a substantial
      intraoperative hemostatic activation in the lung capillaries, which is the
      primary target organ for venous blood-borne bone-marrow debris. Soft-tissue
      surgery and vascular surgery seem to induce less systemic activation of
      coagulation and fibrinolysis.

PMID- 9161902
TI  - Hemostatic-endothelial interactions: a potential anticoagulant role of the
      endothelium in the pulmonary circulation during cardiac surgery.
AB  - The use of extracorporeal circulation during cardiopulmonary bypass (CPB)
      procedures is associated with significant morbidity and mortality. Exposure of
      blood to the foreign surface of the extracorporeal circuit results in activation
      of complement, kinin, fibrinolytic and coagulation systems as well as cellular
      mediators of inflammation. Without the use of anticoagulants, the extracorporeal
      circuit would clot; high-dose heparin prevents coagulation, but activation of the
      coagulation system and consequent thrombin generation still occur. During CPB,
      the lungs are effectively removed from the circulation, and, hence, heparinized
      blood remains static within the pulmonary vasculature for this period. It was
      postulated that under these conditions, the hemostatic system may become
      activated and could contribute to pulmonary dysfunction in some patients after
      CPB. However, it appears that during CPB interactions among heparin, the
      hemostatic system, and the endothelium may exert a protective effect, at least
      against activation of the tissue factor coagulation pathway. In this article, the
      effect of CPB on the coagulation system, with particular reference to changes in
      coagulation proteins occurring in the pulmonary vasculature, are reviewed.

PMID- 9161903
TI  - Elimination of drugs and toxins during cardiopulmonary bypass.
AB  - Cardiopulmonary bypass (CPB) creates a myriad of pharmacological and
      physiological changes. Some of these changes have been studied in isolated in
      vitro studies. Integrating an in vitro system into an in vivo process is so
      complicated that many pharmacological studies simply avoid the bypass period. For
      the most part, the studies that do examine the bypass period deal with a single
      drug, reporting how it does or does not produce a predicted concentration on
      initiation, maintenance and termination of CPB. Based on the isolated results of
      these studies, this review hypothesizes a model that explains how different
      substances interact with the CPB system. A summary of the review's findings
      include the following: 1) drugs with a smaller volume of distribution are more
      likely to be effected; 2) the pharmacokinetic effects of lipophilic drugs undergo
      more alterations than hydrophilic drugs; and 3) protein binding minimizes
      alterations of lipophilic drugs and increase alterations of hydrophilic drugs.

PMID- 9161904
TI  - The inflammatory response and extracorporeal circulation.
AB  - Defining the cause of organ and tissue dysfunction associated with the use of
      perfusion systems will produce methods of prevention or treatment and improve
      patient outcome. The problem is the plethora of triggers, effectors, and
      mediators in this process, which can now be measured. Each new measureable
      compound becomes another biochemical "smoking gun" without physiological data to
      show any relevance to the human problem. This review critically compares and
      contrasts the role of certain, largely novel, initiation, amplification, and
      cytotoxic mechanisms in the inflammatory response of the myocardium and pulmonary
      systems after a period of cardiopulmonary bypass. The available evidence strongly
      points to the process being different for each of these tissue beds. These data
      suggest that ensuring normal lung and heart functions after surgery will require
      separate therapeutic strategies.

PMID- 9161905
TI  - The inflammatory response to cardiopulmonary bypass.
AB  - The inflammatory response to cardiopulmonary bypass is the product of a complex
      interplay of humoral and cellular components. Contact activation cascades, the
      complement system, and cytokines comprise the humoral elements and interact in
      such a way as to propagate their own cascades and to activate the cellular
      elements. Neutrophils and endothelial cells are the cellular components and
      become involved after their "activation" by the humoral mediators. Neutrophil
      endothelial cell adherence is the initial step of the cellular inflammatory
      response and is promoted by the expression of specific adhesion molecules on the
      surfaces of both of these cells leading to the emigration of neutrophils into the
      extravascular space where they release toxins that damage surrounding tissues.
      The resulting organ dysfunction produces the clinical picture referred to as the
      "postperfusion syndrome." Strategies to attenuate this response include the
      administration of corticosteroids, aprotinin, and anticytokine monoclonal
      antibodies, as well as various modifications of the bypass circuit. The existence
      of multiple pathways to trigger this inflammatory response hampers efforts at its
      attenuation and leaves much investigation to be done as the quest to understand
      the body's inflammatory response to cardiopulmonary bypass continues.

PMID- 9161906
TI  - The influence of cardiopulmonary bypass on cytokines and cell-cell communication.
AB  - Cardiopulmonary bypass (CPB) is characterized by systemic endotoxemia immediately
      after its onset as well as the systemic release of proinflammatory cytokines,
      including tumor necrosis factor-alpha and the interleukins 1 and 6. Recent
      studies document that increased morbidity and mortality rates correlate with
      elevated systemic concentrations of these proinflammatory cytokines during adult
      and neonatal sepsis, following thoracoabdominal aortic aneurysm repair, as well
      as following CPB. These proinflammatory cytokines induce increased neutrophil and
      endothelial surface adhesive molecule expression, thereby promoting enhanced
      neutrophil-endothelial adherence. Increased neutrophil-endothelial adherence and
      subsequent neutrophil organ binding are thought to be a "final common pathway" of
      organ injury during clinical inflammatory conditions. Proinflammatory cytokines
      also increase cellular expression of inducible nitric oxide synthase, thus
      increasing cellular production of nitric oxide, a known inflammatory mediator.
      This review discusses recent evidence of the adverse effects of proinflammatory
      cytokine release during CPB and therapeutic modalities that can reduce the
      systemic concentrations of these mediators of inflammation.

PMID- 9161907
TI  - Biocompatibility in cardiopulmonary bypass.
AB  - Recent advances in surgical techniques and perfusion technology allow cardiac
      operations to be performed routinely with low mortality rates. However, patients
      undergoing cardiac operations with cardiopulmonary bypass (CPB) are still
      associated with bleeding disorders, thrombotic complications, massive fluid
      shifts, and the activation of blood components that are collectively known as the
      whole body inflammatory response. In this review, the effect of cardiopulmonary
      bypass on various humoral and cellular components of blood is examined. Blood
      activation caused by interaction with artificial materials of extracorporeal
      circuit and by material-independent stimuli is discussed. Methods to control
      blood activation during and after cardiopulmonary bypass are described. These
      include surface modification of extracorporeal circuit, control of flow dynamics
      in the circuit, pharmacological intervention, and the use of extracorporeal
      devices to remove inflammatory mediators. Recent findings on the effects of
      heparin-coated circuits on inflammatory response and clinical outcome are
      reviewed. It appears that the causes of inflammatory response to cardiopulmonary
      bypass are multifactorial and that an integrated strategy is needed to control
      and eliminate the negative effects of CPB.

PMID- 9161908
TI  - Perfusion safety: past, present, and future.
AB  - Safe cardiopulmonary bypass has been paramount from its first use in the early
      1950s until the present. The original perfusion circuits incorporated complex
      feedback loops and multiple safety devices. As circuits improved and became
      simpler to operate, advances in safety did not always keep pace. Surveys have
      illustrated areas that needed improvement and extra attention has been focused on
      those problems. As the field of perfusion evolved, so has the perfusionist.
      Perfusion has progressed from on-the-job training to formalized training,
      certification, and accreditation, and is now approaching national
      standardization. As the computer age proceeds, the use of safety devices and
      feedback mechanisms whose developments have been aided by the newly available
      technologies increases. As the 21st century approaches, cardiopulmonary bypass
      will continue to become safer, but the perfusionist must continue to stay up-to
      date in education and remain vigilant while in the operating room.

PMID- 9161909
TI  - Current concepts in cardiopulmonary resuscitation.
AB  - The "chain of survival" is important in the resuscitation of a patient who has
      had a cardiac arrest. The provision of Basic Life Support (BLS) and Advanced
      Cardiac Life Support (ACLS) is essential in this "chain of survival." Both BLS
      and ACLS have undergone several revisions since their initial inception. This
      article reviews (1) the current established and investigational issues of
      cardiopulmonary resuscitation, (2) the incidence and outcomes of anesthesia
      related cardiac arrest, (3) the use of cardiopulmonary bypass in resuscitation,
      and (4) cerebral protection during and after resuscitation.

PMID- 9161910
TI  - Machine milking of Ostfriesian and Lacaune dairy sheep: udder anatomy, milk
      ejection and milking characteristics.
AB  - Mammary cistern anatomy derived from ultrasound measurement, milk ejection in
      response to exogenous oxytocin and oxytocin release and milking characteristics
      with and without manual prestimulation in early (months 2-4) and late (months 5
      8) lactation were investigated in Lacaune and Ostfriesian dairy ewes. Vertical
      ultrasound cisternal cross sections of the cisternal cavities did not differ in
      the two breeds, whereas the cisternal area fraction located lower than the exit
      into the teat channel was larger in Ostfriesian than in Lacaune sheep. The
      cisternal area enlarged within 1 min in response to i.v. oxytocin injection,
      indicating milk ejection. During milking, oxytocin concentrations in Lacaune
      generally increased dramatically within 0.5 min from the start of prestimulation
      or milking, whereas only slight or no oxytocin release was detected during
      milking without prestimulation in Ostfriesian ewes. Prestimulation induced
      oxytocin release in Ostfriesian sheep within 1-2 min after the start of milking,
      indicating delayed response to stimulation. Two peaked milk flow curves were
      observed when oxytocin release and milk ejection occurred only after removal of
      cisternal milk. This type of milk flow was more frequent in Ostfriesian than in
      Lacaune ewes and was reduced in both breeds by prestimulation, while the
      frequency of one peaked milk flow curves increased. During the course of
      lactation, milk yield, main milk fraction and milk flow rates decreased, while
      stripping yield was almost unchanged. Although milk yield was similar in both
      breeds, milk flow was lower and stripping yield was higher in Ostfriesian than in
      Lacaune ewes. We conclude that milk ejection in ewes occurred in response to
      elevated oxytocin concentrations. In Ostfriesian ewes reduced and delayed
      oxytocin response to teat stimulation resulted in milk ejection only during
      stripping. Therefore, and probably because a larger volume of the cistern was
      located below the teat exit in the Ostfriesian breed, stripping yield was higher
      in Ostfriesian than in Lacaune sheep.

PMID- 9161911
TI  - Influence of supplementary fish oil and rumen-protected methionine on milk yield
      and composition in dairy cows.
AB  - The effects of a daily supplement of 300 ml fish oil and 20 g rumen-protected
      methionine, alone or in combination, were investigated in mid-lactation cows
      receiving a maize silage-based diet ad lib. Fish oil significantly decreased feed
      intake, increased milk yield, decreased protein and casein concentrations, and
      especially fat concentration (by 13.1 g/kg) and output. Fat concentration
      decreased more in primiparous than in multiparous cows. Methionine
      supplementation increased protein and casein concentrations and outputs. No
      significant interaction between oil and methionine supplementation was found on
      milk composition. Treatments did not modify live weight or body condition
      changes, or lactose and non-casein nitrogenous compounds in milk. Oil plus
      methionine supplementation made it possible to decrease milk fat content without
      changing protein content.

PMID- 9161912
TI  - Effects of dietary calcium soaps of unsaturated fatty acids on digestion, milk
      composition and physical properties of butter.
AB  - Dairy cows fitted with ruminal, duodenal and ileal cannulas were utilized to
      investigate the effects of feeding with Ca soaps (CaS) of palm fatty acids (FA)
      and rapeseed FA. Diets compared were control diet based on maize silage and
      concentrate, and two diets with 40 g CaS of palm oil FA or rapeseed oil FA/kg
      diet, replacing part of the concentrates of the control diet. Total
      digestibilities of dry matter, fibre and fat, and ruminal fermentation were not
      significantly altered by giving CaS; the extent of ruminal biohydrogenation of
      total unsaturated C18 FA was significantly reduced by both CaS diets. Apparent
      intestinal digestibility of FA was not different among diets, although the amount
      of FA absorbed with the CaS diets was twice that with the control diet. No
      difference among diets was observed for milk production, or fat and protein
      contents. Giving CaS diets decreased the proportions of 4:0 to 14:0 FA in milk
      fat, and increased cis-18:1n-9, compared with control diet. The rapeseed diet
      lowered the content of 16:0, and increased the contents of 18:0 and trans-18:1n
      7. CaS diets did not result in a marked increase of polyunsaturated FA content in
      milk fat. Butter from cows fed on the CaS diets contained more liquid fat at 6
      and 14 degrees C than butter from the cows fed on the control diet. Incorporating
      CaS, particularly those from rapeseed, in dairy cows' diets increased C18 FA in
      milk and improved butter spreadability.

PMID- 9161913
TI  - Immunohistochemical investigation into the distribution pattern of myoepithelial
      cells in the bovine mammary gland.
AB  - The distribution pattern of myoepithelial cells in the bovine mammary gland was
      investigated by an immunohistochemical technique, using monoclonal antibodies
      against cytokeratins 5, 6 and 18 and cytokeratins 8 and 14 and against alpha
      smooth-muscle actin filaments. Myoepithelial cells were shown to be present as a
      continuous basal cell layer in the intralobular ducts, as discontinuous cell rows
      in the basal cell layer of the interlobular ducts, and as single cells dispersed
      in the basal cell layer of the quarter cisterns; while they were apparently
      absent in the teat cisterns. Unlike the case with myoepithelial cells of the
      human breast, anti-cytokeratin 14 was less specific as a marker of bovine
      myoepithelial cells than was anti-alpha-smooth-muscle actin.

PMID- 9161914
TI  - Effects of stage of lactation, milk protein genotype and body condition at
      calving on protein composition and renneting properties of bovine milk.
AB  - The lactational variation in milk protein composition and renneting properties
      and their relationship to the cow's body condition at calving were investigated
      in 39 Danish Holstein first lactation cows fed on a well balanced standard diet.
      All milk characteristics measured were significantly affected by stage of
      lactation (P < 0.01). Casein as a proportion of total milk nitrogen reached a
      maximum in mid lactation. The proportion of alpha s- and kappa-casein in total
      casein decreased and the proportion of beta-casein increased systematically
      during lactation while the proportion of gamma-casein was lowest in mid
      lactation. The alpha-lactalbumin content of milk and its proportion of total whey
      proteins decreased during lactation. Renneting time was highest and curd firmness
      lowest in mid lactation. These results appeared to reflect a low degree of
      proteolysis in late-lactation milks compared with several other investigations,
      probably because of the good nutritional state of the cows. The body condition at
      calving affected proteolysis and the renneting properties of milk. A good body
      condition increased the content of whey protein in total milk nitrogen and of
      gamma-casein in total caseins (P < 0.05); in addition, curd firmness was improved
      (P < 0.01) and aggregation time was reduced (P < 0.05). We suggest that these
      effects were related to the fat metabolism and energy status of the cows during
      lactation. The interrelationships between the milk characteristics were evaluated
      by factor analysis to support the interpretation.

PMID- 9161915
TI  - Isolation of genomic DNA from milk samples by using Chelex resin.
AB  - A rapid procedure for isolating genomic DNA from milk samples has been devised,
      based on the use of Chelex resin. By using this protocol, genomic DNA was
      extracted from milk samples from 15 cows and 15 goats. The suitability of these
      DNA preparations as a template for performing the polymerase chain reaction (PCR)
      was tested by amplifying three different loci of the bovine genome: exon 4 of the
      kappa-casein gene and the INRA5 and INRA23 microsatellites, together with two
      others: exon 19 of the alpha s1-casein gene and exon 2 and part of intron 2 of
      the DRB gene of the caprine genome. No amplification products could be obtained
      from any sampless at 30 cycles. In contrast, at 45 cycles the number of amplified
      samples ranged from 86 to 100% and at 65 cycles all the DNA targets were
      amplified, indicating that the number of cycles was a critical factor to be
      optimized for obtaining the desired PCR target. These results suggest that this
      method may be a useful tool for analysing genetic polymorphism at the DNA level
      by PCR and relating it to milk composition and other traits of economic interest.

PMID- 9161916
TI  - Folate and folate-binding protein content in dairy products.
AB  - Recent findings suggest a protective role for folates in the reduction of neural
      tube defects and possibly also coronary heart disease and cancer. Consequently,
      an increase in the daily intake of folates is warranted, which emphasizes the
      need for quantitative as well as qualitative measurements of dietary folates.
      Milk plays an important part in the food chain in many Western countries today.
      Several studies suggest that folate-binding proteins might have an impact on
      folate absorption and therefore their concentrations are also important. The mean
      concentration of the predominant form of folate, 5-methyltetrahydrofolate (5
      CH3THF), was determined using HPLC in thirteen selected dairy products; skim milk
      powder, two pasteurized milks, UHT milk, two fermented milks, three whey products
      and four different cheeses. All results were corrected for recovery by spiking
      the samples with 5-CH3THF. Effects of storage of dairy products on 5-CH3THF
      concentrations were also investigated; generally small and insignificant
      fluctuations were found, except for hard cheese, in which 5-CH3THF decreased
      significantly. There was a significant seasonal variation in the folate
      concentration of pasteurized milk which peaked in the summer months. The
      concentrations of folate-binding protein in skim milk powder and pasteurized milk
      analysed using an enzyme-linked immunosorbent assay were similar. UHT milk and
      fermented milk, both of which are processed at temperatures > 90 degrees C,
      contained significantly lower concentrations of folate-binding protein.

PMID- 9161917
TI  - Binding of Staphylococcus aureus to milk fat globules increases resistance to
      penicillin-G.
AB  - The susceptibility to penicillin-G of Staphylococcus aureus strains that cause
      mastitis was tested in milk and in Iso-sensitest broth (ISB): The minimal
      inhibitory concentrations (MIC) of beta-lactamase-positive strains in milk were
      10-100-fold those in ISB, whereas the MIC of beta-lactamase-negative strains in
      milk were some 10-fold those in ISB; beta-lactamase production was induced by
      milk in beta-lactamase-positive strains. Much of the increase in resistance to
      penicillin-G caused by milk can be attributed to milk fat globules; the increase
      in resistance was related to the binding capacity of the bacteria to milk fat
      globules as well as to capsule formation by the bacteria. It appears that the
      binding of the staphylococci to the fat globules and bacterial capsule formation
      resulted in a biofilm type of growth. In this case, the staphylococci behaved
      differently from the planktonic type of growth in artificial broth medium in
      which antibiotic susceptibility testing is usually carried out.

PMID- 9161918
TI  - Temperature characterization of psychrotrophic and mesophilic Bacillus species
      from milk.
AB  - A total of 50 isolates of Bacillus spp. and one reference strain were
      investigated for their growth at 6.5 degrees C for 10 d, 30 degrees C for 3 d and
      40 degrees C for 2 d. The results obtained differentiated three physiological
      groups: one clearly psychrotrophic (able to grow at 6.5 degrees C in 10 d, but
      not at 40 degrees C in 2 d), one intermediate in psychrotrophy (it grew at both
      40 and 6.5 degrees C) and one mesophilic (capable of growth at 30 and 40 degrees
      C, but not at 6.5 degrees C). The proportion of strains in the second group was
      higher among isolates of B. cereus than for other Bacillus spp. However, the
      proportion of real mesophilic strains was lower for B. cereus isolates.
      Psychrotrophic B. cereus grew better at both 6.5 and 30 degrees C than other
      psychrotrophic Bacillus spp. Using eight strains, a correlation between
      differential growth at mesophilic temperatures (count at 30 degrees C minus count
      at 40 degrees C) and a standard psychrotrophic count at 6.5 degrees C for 10 d (r
      = 0.95) was obtained in mixed cultures when the psychrotrophic flora count was <
      or = 1 log (cfu/ml) lower than the mesophilic count.

PMID- 9161919
TI  - Monitoring the microbiology of high quality milk by monthly sampling over 2
      years.
AB  - The concentrations of seven types of microorganism in the milk produced by farms
      using high quality milking procedures were monitored monthly. The most commonly
      encountered bacterium was Pseudomonas, whose concentration varied greatly between
      samples, but lactococci, lactobacilli and yeasts were also present at more stable
      concentrations. Staphylococcus aureus and beta-glucuronidase-positive Escherichia
      coli were occasionally detected. Listeria monocytogenes was found in the samples
      from only one farm, while Yersinia enterocolitica was never detected. There were
      seasonal variations in the concentrations of lactobacilli and yeasts over the 2
      years monitored. The changes in certain bacteria (Lactococcus, Lactobacillus) on
      any given farm were very similar from one year to the next. The microbiological
      characteristics of the milk from the farms examined seemed to be fairly constant.
      The profiles of some bacteria used for cheesemaking were relatively stable over
      time. It thus seems that the milk provided by different producers could be typed.

PMID- 9161920
TI  - Influence of whey and purified whey proteins on neutrophil functions in sheep.
AB  - The effects of ruminant whey and its purified fractions on neutrophil chemotaxis
      and superoxide production in sheep were studied. Both colostral whey and milk
      whey were found to inhibit chemotaxis regardless of whether they were autologous
      or homologous, but the inhibitory effects were abolished by washing neutrophils
      with culture medium before their use in the chemotaxis assay. Colostral whey and
      milk whey also inhibited the chemotactic activity of zymosan-activated serum.
      Whey fractions of various degrees of purity such as lactoferrin, lactoperoxidase,
      lactoferrin-lactoperoxidase, alpha-lactalbumin, bovine serum albumin and whey
      protein concentrate were then studied. While none of these proteins showed any
      effects on chemotaxis, lactoferrin-lactoperoxidase and whey protein concentrate
      were found to have an enhancing effect on superoxide production in a dose
      dependent manner. Our results provide information on the modulatory role of
      ruminant milk proteins in inflammatory responses and warrant future
      investigation.

PMID- 9161921
TI  - Disability: the place of judgement in a world of fact.
AB  - Ways of viewing disability, of developing research questions, of interpreting
      research results, of justifying research methodology, and of putting policies and
      programmes in place are as much about ideology as they are about fact. It is
      important to recognize how significant this is to research generally and to the
      field of intellectual disability in particular. The roots of scientific and socio
      economic justification for the allocation of research funding, and of political
      (or state) action based on research findings can be found in identifiable and
      shifting ideological frameworks. Therefore, to understand the field, it is useful
      to explore the social and scientific formulations of disability which underpin
      the research agenda, and the ways of knowing disability.

PMID- 9161922
TI  - Old World--new territory: European perspectives on intellectual disability.
AB  - People with intellectual disability share the mixed fortunes of the diverse
      countries in that they live, as well as the social and political changes that
      mark life in Europe at the close of the twentieth century. The European Union
      exerts its influence through common policies and centrally funded initiatives
      which promote the social and vocational integration of people with intellectual
      disabilities. At the same time, many countries in Central and Eastern Europe are
      building a new and as-yet untested social order. This paper outlines the
      distinctive features of European identity. Some of the gains already achieved on
      behalf of Europeans with intellectual disability are presented, as well as some
      of the problems which continue to threaten their well-being and inclusion. It is
      suggested that partnerships between countries and regions can help to chart new
      territory for citizens of the Old World.

PMID- 9161923
TI  - Nordic contributions to disability policies.
AB  - The most spectacular contribution from the nordic countries to intellectual
      disability policy is probably the idea of normalization, but it is not the
      simplistic notion that can be inferred from international debate. Its major
      significance may have been to act as an inspiring catchword for the important
      trend away from institutions into integrated living. However, it is more fully
      understood when seen in the concrete context where it has successively developed,
      and been critically analysed and tested in operation. Scandinavian sociologists
      and psychologists--as well as politicians--were also among the first to use the
      concept of quality of life for analysis of social policy, including intellectual
      disability. The primary medium for implementation has been legislation, where the
      dominant difficulty is to find a balance between security and freedom, protection
      and self-determination. Through this process, the role of social engineering in
      the welfare state, based on humanistic ideas of solidarity, can be followed into
      today's emphasis on individual influence and participation.

PMID- 9161924
TI  - Defining and applying the concept of quality of life.
AB  - Quality of life has been increasingly used as a scientific concept in literature
      embracing a wide range of target groups and populations as a whole.
      Conceptualizations vary, but there is much common ground concerning the domain
      content embraced by the term. Commentators are also clear that account needs to
      be taken of both objective life conditions and subjective personal appraisals,
      and the fact that what is important to each person varies. A synthesis of these
      perspectives provides a model of quality of life which integrates objective and
      subjective indicators and individual values across a broad range of life domains.
      Life domain issues may be categorized within six areas: physical, material,
      social, productive, emotional and civic well-being. Whatever its precise
      specification, the model is put forward as a framework for organizing measurement
      relevant to the quality of life concept rather than as a blueprint for deriving
      the ultimate single instrument. There is still a need for methodological
      flexibility. The pre-eminent aim is to relate the fine grain of the experience of
      individuals with disability to that of the wider world.

PMID- 9161925
TI  - Intellectual disability and ageing: ecological perspectives from recent research.
AB  - Ageing in people with intellectual disabilities has become a central concern of
      service providers and research workers during the past 20 years. Their emergence
      as an identifiable population of older people with intellectual disabilities
      reflects, in part, improvements in medical and social service provision. However,
      interest in this group is primarily a reflection of the fact that, despite
      services developed in the light of principles of normalization, they remain
      readily identifiable as people in receipt of specialist intellectual disability
      services, in consequence typically clearly differentiated from the mainstream of
      older people generally. Analysis of this situation and other factors impacting on
      older people with intellectual disabilities can be undertaken through the use of
      ecological models conceptualized in terms of interacting, nested ecologies. The
      emergence of research on the impact of cultural influences on family carers and
      service provision is addressed within the framework of the ecological model, and
      methodological cautions are offered. The enduring the role of family carers and
      their motivation to continue caring is described.

PMID- 9161926
TI  - The remediation of executive functions in children with cognitive disorders: the
      Vygotsky-Luria neuropsychological approach.
AB  - The demands of methods of effective remediation arising from the Vygotsky-Luria
      approach to the structure and development of higher mental functions are
      discussed. These demands suggest the structuring of a therapeutic interaction in
      accordance with the rules of the internalization process, taking into account a
      weak component of the child's functional systems and the emotional involvement of
      a child in that interaction. In order to provide a theoretical framework for
      developing methods of executive function remediation, the approaches of Vygotsky
      and Luria, as well as modern views on the structure and development of executive
      functions, are discussed. The Method of Numerical Sequence is presented as an
      example of the application of the general principles discussed above. The Method
      of Numerical Sequence provides a background for following the development of
      successive processing, programming and planning, and can be considered as a
      complement to the development of the metacognitive aspects of self-regulation.
      This method was verified experimentally in groups of 5-8-year-old children with
      intellectual disability.

PMID- 9161927
TI  - Diagnosis of dementia in individuals with intellectual disability.
AB  - The foremost impediment to progress in the understanding and treatment of
      dementia in adults with intellectual disability is the lack of standardized
      criteria and diagnostic procedures. Standardized criteria for the diagnosis of
      dementia in individuals with intellectual disability are proposed, and their
      application is discussed. In addition, procedures for determining whether or not
      criteria are met in individual cases are outlined. It is the intention of the
      authors, who were participants of an International Colloquium on Alzheimer
      Disease and Mental Retardation, that these criteria be appropriate for use by
      both clinicians and researchers. Their use will improve communication among
      clinicians and researchers, and will allow researchers to test hypotheses
      concerning discrepancies in findings among research groups (e.g. dementia
      prevalence ranges and age of onset).

PMID- 9161928
TI  - A story description task in children with Down's syndrome: lexical and
      morphosyntactic abilities.
AB  - A story description task was used to elicit short stories by 10 Italian children
      and adolescents with Down's syndrome and 10 normal children matched on mean
      length of utterance (MLU). Data analysis focused on a subset of lexical,
      morphological and syntactic aspects of language use. The results show that the
      subjects with Down's syndrome and their normal matches use a similar lexical
      repertoire. However, the two groups differ with respect to omissions of free
      morphemes, and some aspects of syntactic and pragmatic abilities. These data on
      Italian subjects corroborate and extend previous findings on other languages:
      despite an extensive repertoire of lexical and grammatical items, subjects with
      Down's syndrome seem unable to use such elements appropriately and consistently
      across contexts.

PMID- 9161929
TI  - Classification, prevalence, prevention and rehabilitation of intellectual
      disability: an overview of research in the People's Republic of China.
AB  - The People's Republic of China is a developing country with all the problems and
      challenges that face such countries all over the world. Progress has been
      hampered by scarcity of resources, and a lack of relevant information and
      appropriate skills, as well as by the stigma traditionally attached to people
      with intellectual disability. The present rapid economic development has made
      possible further improvement and expansion of educational opportunities, and
      health and rehabilitation services. According to a recent census and sample
      surveys conducted in the People's Republic of China, the overall prevalence rate
      of people with disabilities was estimated to 4.9%. Thus, China has more
      individuals with disabilities than any other country in the world. According to
      these figures, the prevalence of intellectual disability in the population is
      approximately 1%. For children younger than 14 years of age, the prevalence is
      around 2%, which accounts for 66% of all handicapped children, making it the most
      frequent childhood disability. Today, the existing medical facilities, and
      educational and social welfare organizations cannot meet the tremendous need of
      care and services. The problems of the large number of disabled children and
      adults are a major challenge for contemporary Chinese society. This paper is
      devoted to research pertinent to intellectual disability in China. With a few
      exceptions, only publications in the English language were included in this
      review, which makes the overview selective rather than comprehensive.
      Publications on classification systems and diagnostic criteria, screening methods
      and assessment instruments, prevalence rates, aetiology and risk factors,
      prevention and intervention efforts, special education, and families with
      children with intellectual disability are presented.

PMID- 9161930
TI  - The effect of the disaster caused by the great Hanshin earthquake on people with
      intellectual disability.
AB  - The vulnerability of people with intellectual disability when services are
      disrupted by a major earthquake is described. The value of an accessible register
      and multiple networks of support at the time of a major disaster is emphasized.

PMID- 9161931
TI  - Current views on the pharmacological properties of the immunomodulator,
      lobenzarit disodium.
AB  - Lobenzarit disodium (LBZ) is an immunomodulator and antioxidative drug developed
      and used successfully in Japan for the treatment of rheumatoid arthritis (RA).
      Studies in animals and humans have shown striking differences between the
      pharmacological profile of LBZ and nonsteroidal antiinflammatory drugs commonly
      used in the treatment of RA. LBZ does not inhibit the biosynthesis of
      prostaglandins and leukotrienes and is ineffective on acute inflammatory
      reactions induced in animals. Therefore, its usefulness in RA is ascribed to
      immunopharmacological properties of the drug. Currently, evidence is available
      that B- and T-lymphocytes are targets of LBZ's actions which regulates the
      functions of these cells. LBZ reduces IgE titers in serum of sensitized mice by
      activating suppressor T-lymphocytes and inhibiting anaphylactic shock induced by
      ovalbumin. These results provide evidence in favor of the potential use of LBZ in
      the treatment of allergic diseases, which must be elucidated in controlled double
      blind clinical trials. The suppressive effects of LBZ on the function of
      activated B cells as well as in the production of anti-DNA antibody have been
      reported. These findings suggest that LBZ may be effective in the treatment of
      other autoimmune diseases such as lupus erythematosus that are also characterized
      by the production of autoantibodies from activated B cells. Recently, an open
      clinical trial in patients with systemic lupus erythematosus supports this point
      of view. Other potential therapeutic uses of LBZ are in autoimmune-related
      diabetes and in autoimmune liver disease which are documented in this review. LBZ
      also selectively antagonizes the contractile responses of isolated rabbit aorta
      strips induced by thromboxane A2-mimetic U-46619. This result provides evidence
      in favor of an antagonist of LBZ at the level of TxA2 receptors and supports the
      potential usefulness of LBZ in some cardiovascular disorders such as
      cardiopulmonary diseases and thrombosis. LBZ is a scavenger of oxygen-free
      radicals such as hydroxyl radicals, superoxide, peroxyl and singlet oxygen. This
      property contributes substantially to its pharmacological and therapeutic profile
      as well as its mechanism of action.

PMID- 9161932
TI  - IgE binding proteins in honey: discussion on their origin.
AB  - Pollen proteins, most frequently from Compositae plants, and glandular enzymes
      from Hymenoptera insects are the only honey allergens involved in every case of
      honey sensitization reported so far. Surprisingly, we found three patients, all
      showing the same pattern of honey sensitization with clinical history, cutaneous
      test and specific IgE clearly positive to honey crude extract but not to the
      aforementioned components. IgE binding bands, mainly at 54, 46, 17 and 16 kDa,
      were recognized by the sera of the three patients on blots following
      electrophoretic separation of a local honey extract under dissociating
      conditions. Attempts to identify these proteins with the most common honey
      allergens by means of SDS-PAGE immunoblotting failed, leaving open the question
      on the origin of protein allergens in cases of honey allergy. Thus, if bee
      derived components are not proven to be involved in honey sensitization, other
      protein sources, such as nectar, should not be disregarded.

PMID- 9161933
TI  - A three-year prospective study of specific immunotherapy to inhalant allergens:
      evidence of safety and efficacy in 300 children with allergic asthma.
AB  - The effectiveness and safety of specific immunotherapy (SIT) in allergic diseases
      such as asthma have increasingly come under question. Some authors advocate
      eliminating SIT as a therapeutic option for allergic patients, since the risks
      associated with this form of asthma may outweigh its positive effects. However,
      in a review of twenty-nine controlled studies in 2077 children and an equal
      number of controls, 27 (93.1%) have shown the effectiveness of SIT in pediatric
      age for the treatment of asthma due to inhalant allergens (p < 0.0001). The scope
      of this study was to ascertain whether this form of therapy is safe and effective
      in pediatrics. 300 children (median age 4.4 years) with asthma due to pollen or
      house dust mite were prospectively followed for three years. They were randomly
      divided into two groups: the study group and control group, being almost equal in
      number of children and clinical characteristics such as sex and age. No child
      suffered severe reactions due to SIT. Children receiving SIT had significantly
      greater reductions in days (p = 0.0001) and nights (p = 0.0005) without asthma
      and drug usage (p = 0.0003), compared with drug-treated children. In addition,
      the number of asthma attacks (p = 0.0001), and the quality of life were
      significantly improved in the study group (p = 0.0001). These findings suggest
      that if suitable allergen extracts are used with close observation of therapeutic
      indications, and children are followed by their doctors as frequently as
      required, SIT is effective in the treatment of pediatric asthma, with few adverse
      effects.

PMID- 9161934
TI  - Specific sensitization to Dermatophagoides pteronyssinus and cutaneous reactivity
      to histamine in Brazilian children.
AB  - The immediate hypersensitivity cutaneous test is a recognized method for
      etiologic diagnosis of allergic diseases. It is easily conducted, painless and
      can be quickly interpreted, making it deal for use with children. However, its
      low positivity in infants limits its use this population. The purpose of our
      study was to evaluate the skin reactivity to atopic and non-atopic children of
      different ages to increasing concentrations of histamine and to an extract of
      Dermatophagoides pteronyssinus (Dpt). Atopic children (A, n = 217) and non-atopic
      children (C, n = 198), under 15 years of age were grouped by age and administered
      skin prick tests. Increasing concentrations of histamine (1, 9, 81 and 243 mg/ml)
      and Dpt (10,000 AU/ml) were applied to the forearm. Skin reactions were recorded
      after 15 minutes and expressed as the mean of the largest wheal and its midpoint
      perpendicular diameter. Cutaneous reactions were observed in the early phases of
      life with a progressive increase observed in both groups. Significant differences
      were noted between the two groups starting at 48 months of life. As the
      concentration of histamine was increased, we observed a higher level of cutaneous
      reactivity in younger children. Comparative analysis of cutaneous reactivity to
      the histamine solution (1 mg/ml) and the Dpt extract showed parallelism between
      them and wheals with diameters larger than 3 mm after 12 months of age. We
      concluded that the skin prick test with Dpt is reliable in atopic children after
      1 year of age. Reactivity to higher concentrations of histamine was observed
      after 3 months of age for all children. However, considering all age groups, the
      skin reactivity in atopic children to histamine (1 mg/ml) was more precocious
      when compared to controls.

PMID- 9161935
TI  - Interstitial pneumonitis induced in guinea pigs by the antigens of Rhizopus
      nigricans.
AB  - Rhizopus nigricans (Rn) is one of the most common members of the Mucorales that
      produces opportunistic infections and hypersensitivity states. Data concerning
      experimental induction in guinea pigs of hypersensitivity pneumonitis with a
      glycoprotein antigen are presented. This antigen was obtained from the mycelial
      and metabolic products of the cultures and was aerosolized during 12 weeks. The
      presence of specific antibodies (IgG and/or IgE) was detected by serological
      techniques; histopathological studies of the lungs showed interstitial
      infiltrates of macrophages and LTCD8+ cells, as revealed by the MoAb used. Single
      non-necrotizing granulomas were characteristic from the tenth week to the end of
      the experiment. The results from this animal model suggest that hypersensitivity
      pneumonitis is a typical delayed-type reaction due to chronic contact with the
      heterologous glycoprotein of Rn. The relation of Rn antigen and the development
      of occupational diseases of the lung such as malt-worker's lung and wood
      trimmer's disease is proposed and discussed.

PMID- 9161936
TI  - Bronchoprovocation with methacholine in children under two years old: a follow-up
      study.
AB  - Fifty-one wheezing babies (WB) under two years of age and 20 controls (C) within
      the same age range were submitted to a bronchial provocation test (BPT) with
      methacholine. The appearance of wheezing on pulmonary auscultation was used to
      determine PCW (provocative concentration of methacholine causing wheezing). For
      all tests, methacholine diluted in saline at increasing concentrations (0.025,
      0.125, 0.25, 0.5, 1.0, 2.5, 5.0 and 10.0 mg/ml) was delivered with O2 (5 ml/min)
      via a face mask. Solution was inhaled through the mouth and nose during two
      minutes of quiet tidal breathing via a nebulizer containing a 2 ml volume. No
      collateral effects were observed, except for tachypnea and tachycardia. There was
      a statistically significant difference between the PCW for WB (2.3 mg/ml) and the
      PCW for C (9.2 mg/ml). A 5 mg/ml concentration of methacholine provides the
      clearest distinction between the WB and C groups. Indeed, we observed that 96% of
      WB and 25% of C demonstrated PCW below this concentration. In the WB group, those
      with mild symptoms had higher PCW values. When the BPT was repeated in 27 WB at
      an 8-month interval, statistically significant differences between the two PCV
      values were observed. The highest PCW values were evidenced in the second BPT.
      The use of BPT with methacholine could establish PCW as a parameter of bronchial
      hyperreactivity in infants.

PMID- 9161937
TI  - Comparative study between skin prick tests and TOP-CAST allergen leukocyte
      stimulation in diagnosis of allergic status.
AB  - A recently developed CAST-ELISA method was applied to determine allergen-induced
      leukocyte stimulation. This method is based on the measurement of
      sulfidoleukotriene secretion by peripheral blood leukocytes previously stimulated
      with specific allergen in the presence of interleukin 3. 24 patients allergic to
      different aeroallergens and some food allergens were included in this study.
      Subjects received no medication 2 weeks before the testing. Leukocytes were
      isolated by dextran sedimentation. After incubation with allergen at two
      concentrations, the cells were centrifuged and the concentration of
      sulfidoleukotrienes in supernatant was determined. The results were expressed in
      pg/ml after subtraction of values of spontaneous sulfidoleukotriene production in
      portions incubated without allergen. We observed a wide range of
      sulfidoleukotriene secretion upon allergen stimulation. Concentrations of
      leukotrienes ranged from 0 to 5780 pg/ml at lower allergen concentration and from
      210 to 5680 at higher allergen concentration. On the basis of observed results,
      we conclude that the better allergen concentration is the higher one because
      there was no appearance of negative cell stimulation. In the lower allergen
      concentration we observed negative results in two cases. Sixteen healthy control
      subjects were also included in this study. Eleven subjects had negative skin
      prick tests (SPT) as well as CAST results. In 5 healthy subjects with positive
      SPT, we also observed positive CAST results in 4 persons. In 1 healthy person
      with positive SPT results, CAST results were negative. We conclude that TOP-CAST
      allergen is a valuable mixture of different aero and food allergens for
      determining the allergic status in patients with suspicious allergic status,
      although it cannot differentiate between health and disease states.

PMID- 9161938
TI  - Increased serum IgE in acute type A, B and delta hepatitis.
AB  - Serum IgE levels have been documented in patients of acute type B hepatitis.
      There are very few studies on serum IgE in acute type A hepatitis and, to our
      knowledge, there are no data on serum IgE in acute delta hepatitis patients. The
      purpose of this study was to measure total IgE levels in 38 patients with acute
      A, B and delta hepatitis and in 181 controls in order to determine the possible
      existence of changes in this parameter in the course of these infections. Our
      results showed a relevant increase in IgE levels in the three groups (hepatitis
      A, B and delta) with respect to the control group. Moreover, the hepatitis B
      group showed increased total serum IgE levels with respect to the hepatitis delta
      group.

PMID- 9161939
TI  - Proliferative responses of lymphocytes to food antigens are useful for detection
      of allergens in nonimmediate types of food allergy.
AB  - Food allergy is clinically classified into two types, immediate and nonimmediate.
      Radioallergosorbent test (RAST) is a sensitive procedure for the diagnosis of IgE
      mediated hypersensitivity but not for other types of hypersensitivity. There is
      not yet a sensitive blood examination for detection of allergens in nonimmediate
      types of food allergy. Of the total number of subjects in our study, twenty-two
      children had nonimmediate types of food allergy (hen's egg, cow's milk, soybean,
      or buckwheat flour), atopic dermatitis, allergic tension fatigue syndrome or
      pulmonary hemosiderosis. For these children, manifestations of the allergy did
      not appear earlier than 2 hours after ingestion of the offending food. Eighteen
      children in the study developed acute urticaria, angioedema, or bronchial asthma
      appearing within 2 hours of the challenge. Fifteen nonatopic healthy children
      were selected as controls. Proliferative responses of peripheral blood
      mononuclear cells (PBMCs) to food antigens were measured in nonimmediate types of
      food allergy. The proliferative responses of PBMCs to each offending food antigen
      in patients with nonimmediate types of food allergy were significantly higher
      than those of healthy controls and patients with immediate types of food allergy,
      respectively. Moreover, in each case with nonimmediate type, the proliferative
      responses to food antigens other than the offending food were not detected. When
      PBMCs were twice stimulated with the offending food antigen, the same results
      were obtained. These results indicate that the proliferative response of PBMCs to
      food antigens is specific to each offending food antigen in nonimmediate types of
      food allergy. Taken together, proliferative responses of PBMCs to each food
      antigen are useful for detection of allergens in nonimmediate types of food
      allergy.

PMID- 9161940
TI  - Fixed drug eruption induced by lidocaine and patch testing.
AB  - Fixed drug eruption (FDE) is a peculiar drug-induced cutaneous reaction, that
      characteristically reappears at the same site when the etiologic drug is
      readministered. We present a case of a 27-year old male who was referred to us
      after two episodes of erythema on the palms, soles, and genital areas with
      posterior desquamation after receiving local anesthetics. Skin tests with
      lidocaine, mepivacaine and bupivacaine were negative. Eight hours after challenge
      with lidocaine the lesions reoccurred. Patch tests with lidocaine on healthy skin
      and residual lesions were negative, but 48 hours later the lesions reappeared on
      the same areas as before. Challenge with mepivacaine and bupivacaine were
      negative.

PMID- 9161941
TI  - Intra- and interexaminer reliability of anthropometric measurements of term
      infants.
AB  - BACKGROUND: The reliability of anthropometric measurements of term infants has
      not been studied sufficiently to determine if these measurements are reliable
      enough to be used in clinical practice and research. This study described the
      intra- and interexaminer reliability of the following anthropometric
      measurements: weight (WT), head circumference (HC), chest circumference (CC),
      abdominal circumference (AC), mid-arm circumference (MAC), and length. METHODS: A
      convenience sample of 50 clinically stable term infants was studied. Two
      examiners obtained the six measurements twice using blank tape measures. The
      order of examiners was randomized and the examiners were masked to their own and
      the other examiners' measurements. RESULTS: The intraexaminer mean absolute
      differences were as follows: WT = 1.88, 3.28 g; HC = 0.29, 0.29 cm; CC = 0.50,
      0.78 cm; AC = 0.71, 0.77 cm; MAC = 0.36, 0.39 cm; length = 0.92, 1.18 cm. The
      interexaminer mean absolute differences were as follows: WT = 1.94, 1.66 g; HC =
      0.37, 0.36 cm; CC = 0.59, 0.72 cm; AC = 0.99, 0.77 cm; MAC = 0.41, 0.57 cm;
      length = 1.57, 1.47 cm. CONCLUSIONS: These findings indicate that intraexaminer
      differences tended to be smaller than interexaminer differences for all measures
      except weight, which remained stable for intra- and interexaminer comparisons.
      These findings also suggest that weight and head circumference were the most
      reliable measures, whereas length and mid-arm circumference were the least
      reliable measures.

PMID- 9161942
TI  - Sucrose permeability in children with gastric damage and Helicobacter pylori
      infection.
AB  - BACKGROUND: Increased permeability to sucrose has been recently shown to be a
      good marker of gastric mucosal damage in adults. METHODS: This test was evaluated
      in 40 children consulting for recurrent abdominal pain and the results were
      correlated with endoscopic and histologic findings and with the presence of H.
      pylori. RESULTS: The gastric mucosa was considered endoscopically normal in 31
      children; 3 had duodenitis and 6 had mild gastritis. Abnormal endoscopic findings
      were associated with increased urinary sucrose excretion (MANOVA F = 7.30; p =
      0.002). In the 6 children with mild gastritis, mean sucrose excretion was twice
      that of controls (0.060 +/- 0.024 vs. 0.029 +/- 0.018, respectively; p = 0.019)
      and significantly higher than the group with duodenitis (0.037 +/- 0.013; p =
      0.038). The specificity and sensitivity of sucrose permeability test for
      detection of gastric damage were 90.3% and 83.3%, respectively. H. pylori was
      detected in 62.5% of children including all patients with mild gastritis, in 2
      out of 3 with duodenitis and 17 out of 31 endoscopically normal controls. No
      differences in sucrose excretion were observed in relation with the presence of
      H. pylori or histological findings in the control group. CONCLUSIONS: Urinary
      sucrose excretion is a good marker of mucosal gastric damage in children and may
      be used as a screening test in large groups of populations.

PMID- 9161943
TI  - Effect of vitamin K1 supplementation on vitamin K status in cystic fibrosis
      patients.
AB  - BACKGROUND: Patients with cystic fibrosis are at risk for impaired vitamin K
      status due to fat malabsorption from pancreatic insufficiency. This study was
      designed to assess vitamin K status and measure the effect of vitamin K1
      supplementation in cystic fibrosis patients. METHODS: Eighteen outpatients
      participated in a crossover study to determine the effect of vitamin K1
      (phylloquinone) supplementation. After obtaining initial data, each subject was
      randomly assigned to either a 4-week study treatment of 5 mg oral vitamin K1
      supplementation per week, or no supplementation and then crossed over to the
      other treatment for a second 4 week period. Plasma, serum and urine samples were
      collected and analyzed pre-study and at the end of each study period. RESULTS:
      The mean concentration of plasma vitamin K1 for the supplemented group was
      significantly higher than the unsupplemented group, [0.34 nmol/L and 0.21 nmol/L,
      respectively (p < 0.05)]. The percent of undercarboxylated osteocalcin increased
      on supplementation from 17% to 31%, (p < 0.005). Prothrombin induced in vitamin K
      absence (PIVKA-II) increased on supplementation from 5 ng/mL to 22 ng/mL, (p <
      0.005). The ratio of urinary gamma-carboxyglutamic acid/creatinine was similar
      for both study periods. CONCLUSIONS: In contrast to other studies in cystic
      fibrosis, this study demonstrated a need for vitamin K1 supplementation. The
      carboxylation state of osteocalcin and PIVKA-II were the most sensitive indices
      of changes in vitamin K1 status. Although the 5 mg vitamin K1/week dose improved
      these vitamin K parameters, normal levels were not achieved.

PMID- 9161944
TI  - Congenital chloride-losing diarrhoea: absence of the anion-exchange mechanism in
      the rectum.
AB  - BACKGROUND: Congenital chloride-losing diarrhoea is characterized by a defect in
      chloride/bicarbonate exchange, which is normally present in the ileum and colon.
      Whether the defect is an absence or a reversal of such an exchange is unclear,
      and we have investigated two young children with the disorder to answer this
      question. METHODS: We used a previously described nonequilibrium rectal dialysis
      method, using different dialysate anion concentrations, to investigate the
      movement of sodium, potassium, chloride, and bicarbonate in the rectum of the two
      children. RESULTS: The results showed that chloride and bicarbonate movements
      were not linked in any active way, and both ions appeared to move passively in
      response to the electrochemical gradients generated. CONCLUSIONS: In the two
      subjects studied, the defect in the rectum appears to be an absence of the normal
      anion exchange mechanism present in the bowel, rather than its reversal.

PMID- 9161945
TI  - A multicentre study on behalf of the European Society of Paediatric
      Gastroenterology and Nutrition Working Group on Acute Diarrhoea. Early feeding in
      childhood gastroenteritis.

PMID- 9161946
TI  - Omeprazole for severe reflux esophagitis in children.
AB  - BACKGROUND: Severe esophagitis is a rare complication of gastroesophageal reflux
      in children. In adults, omeprazole therapy of severe erosive esophagitis has
      become the gold standard short-term treatment of the disease. In children, data
      on its use are limited, and problems about the dosage are unresolved. The aim of
      this study was to evaluate the efficacy of a simplified, body-weight-based daily
      dosage of omeprazole in children with severe esophagitis. METHODS: Ten children
      (median age 75.6 months; range 25-109 months) with severe esophagitis were
      prospectively investigated. All patients were evaluated by endoscopy, histology,
      and 24-h pH-metry study before and after 3 months of omeprazole. The starting
      dose of omeprazole was 20 mg as a single daily dose in children weighing less
      than 30 kg, and 40 mg daily for those weighing over 30 kg. RESULTS: A significant
      improvement in all the children was demonstrated after 3 months of treatment by
      clinical, endoscopic, and pH-metry assessment. However, histologic study failed
      to show significant improvement of both inflammatory and hyperplastic findings.
      Relapse occurred in six of 10 patients after discontinuation of therapy.
      CONCLUSIONS: Omeprazole is effective in the short-term treatment of severe
      oesophagitis in children. The daily dose of the drug could be easily based on the
      body weight. The persistence of histologic features of esophagitis in spite of
      clinical and endoscopic healing could be an indicator of poor outcome.

PMID- 9161947
TI  - Lipoprotein(a) phenotypes in Japanese children: a cohort study.
AB  - BACKGROUND: Elevated serum lipoprotein(a) [Lp(a)] concentrations have been
      demonstrated to be associated with cardiovascular diseases due to premature
      atherosclerosis. However, the association of Lp(a) phenotypes with the
      development of these diseases remains largely unexplored. METHODS: We analyzed
      the population-based frequencies of serum Lp(a) phenotypes in 269 Japanese
      children aged 8-13 years in one community. According to the different
      apolipoprotein(a) [apo(a)] electrophoretic mobilities, Lp(a) was classified into
      seven single-band and respective double-band phenotypes. Each individual
      expressed a single (homozygotic) or a double band (heterozygotic). RESULTS: The
      serum Lp(a) concentration frequency distribution was skewed toward lower levels
      with a mean +/- SD of 15.5 +/- 18.0 mg/dl and a median of 11.0 mg/dl. The Lp(a)
      phenotype frequencies revealed that the frequency of double-band phenotype
      expression (55%) was higher than that of single bands (44%) and that the
      frequency of phenotypes representative of low molecular weight apo(a) was very
      low (2%). The mean serum Lp(a) concentration of the double-band-expressing
      subjects was higher than that of subjects with the single-band phenotype (20.1 +/
      19.9 vs. 10.5 +/- 15.9 mg/dl, p < 0.01). CONCLUSIONS: These findings of Lp(a)
      phenotypes in children seemed to differ from those in Japanese adults in another
      study; contrary to expectation, the predominant Lp(a) phenotypes found in
      children were those frequently associated with cardiovascular diseases in adults.
      Thus, it is speculated that children whose Lp(a) phenotypes remain unchanged
      during the transition to adulthood may show an increased susceptibility to
      cardiovascular disease, although the nutritional effects on the Lp(a) phenotypes
      cannot be neglected.

PMID- 9161948
TI  - Digestion of proteins in human milk, human milk fortifier, and preterm formula in
      infant rhesus monkeys.
AB  - BACKGROUND: There is limited information in the literature on the capacity of the
      preterm infant to digest human and bovine milk proteins. We therefore studied in
      vivo the luminal phase of the hydrolysis of proteins in human milk, human milk
      fortifier, and preterm formula in preterm rhesus monkeys and in infant rhesus
      monkeys at 6 weeks and 7 months of age. METHODS: Protein hydrolysis was followed
      by polyacrylamide gradient gel electrophoresis and electroimmunoassay. The serum
      level of absorbed unhydrolyzed human alpha-lactalbumin was measured by a
      radioimmunoassay method. Trypsin and elastase activities in duodenal contents
      were measured before and after the meal. RESULTS: In 6-week-old monkeys, the
      enzyme activities decreased by 50% postprandially, whereas they increased in 7
      month-old monkeys. In preterm and in 6-week-old monkeys, hydrolysis of human and
      bovine whey proteins was slow, and in 6-week-old monkeys, 30-50% of the proteins
      could still be detected immunochemically in duodenal contents after 60 min. At
      these ages, serum level of absorbed alpha-lactalbumin were high. At 7 months of
      age, no or small (lactoferrin and bovine serum albumin) amounts of the proteins
      could be detected in duodenal contents after 15 min. At this age alpha
      lactalbumin was not measurable in serum. CONCLUSIONS: The low capacity to digest
      whey proteins in suckling monkeys may depend upon an immaturity of the exocrine
      pancreas to respond to secretogogues.

PMID- 9161949
TI  - The estimated incidence of cystic fibrosis in Japan.
AB  - BACKGROUND: It is believed that the incidence of cystic fibrosis (CF) among
      Asiatic races, including the Japanese, is very rare. This epidemiological study
      was carried out to investigate the incidence of CF in Japan. METHODS: We
      collected literature describing CF cases among pure Japanese and found 124 cases
      reported as CF during the 43 years from 1951, when the first case was reported,
      to 1993. Only 104 cases (57 male and 47 female patients) of 124 cases met our
      diagnostic criteria. RESULTS: A simple calculation based on the number of
      reported CF cases and of live births after 1980 suggested that the incidence of
      CF is about 1 in 350,000 in the Japanese population. Twenty-nine (27.9% of the
      total) of 30 patients diagnosed in the neonatal period presented symptoms of
      meconium ileus, an incidence higher than that reported for the white population.
      CONCLUSIONS: Our study results suggest that the incidence of CF in the Japanese
      population is even rarer than had been estimated before and that there is a
      genetic difference between northern European and Japanese populations.

PMID- 9161950
TI  - Progressive familial intrahepatic cholestasis among the Arab population in
      Israel.
AB  - BACKGROUND: Progressive familial intrahepatic cholestasis, which constitutes a
      heterogeneous group of imperfectly delineated syndromes and appears to be
      inherited as an autosomal recessive condition, has not been hitherto reported
      from the Middle East, in spite of the high rate of consanguineous marriage in
      this region. METHODS: Sixteen affected children from six Israeli Arab families
      were evaluated over 30 years. All were born to consanguineous parents. RESULTS:
      Jaundice appeared during the first 3 weeks of life in 15 babies. When first
      referred, 10 had hepatomegaly and nine had splenomegaly. A progression toward
      cirrhosis was the rule. Serum levels of conjugated bilirubin, liver enzymes, and
      alkaline phosphatase were raised; gamma-glutamyl transpeptidase levels were
      normal in all three infants in whom it was examined, but elevated in two siblings
      of another family at ages 2 and 3 years. No abnormal bile acids were detected in
      the serum and urine of patients. Histologic examination of the liver showed giant
      cell transformation, paucity of intrahepatic bile ducts, cholestasis, fibrosis,
      or cirrhosis. The pattern of liver pathology differed at times among affected
      members within the same family. Therapeutic trials with phenobarbital,
      cholestyramine, or ursodeoxycholic acid were ineffective. Survival of the
      patients was from 5 to 18 months in four families; in the other two families,
      three children received liver transplants, and one is awaiting liver
      transplantation. CONCLUSIONS: Progressive familial intrahepatic cholestasis
      should be included in the differential diagnosis of infants with cholestatic
      jaundice of unknown etiology, especially those born to consanguineous Arab
      parents.

PMID- 9161951
TI  - Correlation of clinical characteristics and small bowel histopathology in celiac
      disease.
AB  - BACKGROUND: Literature information regarding clinical and histological correlates
      in celiac disease is limited. The present study was designed to assess the value
      of various clinical parameters in predicting the severity of small bowel
      histopathology. METHODS: Small bowel biopsy specimens of 59 children with
      established celiac disease (ESPGAN criteria) were evaluated blindly. Morphology
      was evaluated based on a common histopathology score. The following clinical
      variables were evaluated: age at diagnosis, duration of symptoms, severity score
      of clinical symptoms, severity score of physical signs, and growth parameters
      (height and weight Z scores). Multiple regression analysis was performed to
      evaluate the relative importance of each clinical parameter. RESULTS: Only three
      clinical variables revealed a significant correlation with the histopathology
      score. The symptom severity score (t = 3.883, p = 0.0003) demonstrated a positive
      correlation. The two others, age at diagnosis (t = 3.076, p = 0.0032) and
      duration of symptoms (t = -2.987, p = 0.0041), revealed a negative correlation.
      CONCLUSIONS: We conclude that more severe clinical symptoms of a shorter
      duration, presented at a younger age, are better predictors of a more severe form
      of small bowel histopathology in children with celiac disease.

PMID- 9161952
TI  - Antibody pattern in childhood celiac disease.
AB  - BACKGROUND: We carried out a study of the antibody pattern in 50 celiac children
      [34 females (F) and 16 males (M); F/M, 2.1], ages 7 months-15 years, compared
      with that in 25 control subjects (13 females and 12 males) of the same age.
      METHODS: IgA and IgG antigliadin antibodies (AGA) were determined with an enzyme
      linked immunosorbent assay technique. IgA anti-R1-reticulin antibodies (ARA) and
      IgA antiendomysium antibodies (EmA) were determined with the fluorescein
      isothiocyanate-conjugate-labeled anti-human immunoglobulin technique. To compare
      sensitivity and specificity, EmA were identified using monkey esophagus and human
      umbilical cord as substrates. RESULTS: While AGA (IgA and IgG) showed a high
      sensitivity but a low specificity, ARA showed a high specificity but a low
      sensitivity. Data on EmA showed a high sensitivity and specificity with both
      tissue sections, with monkey esophagus being more sensitive (96%) and umbilical
      cord more specific (100%). CONCLUSIONS: Our results confirm the importance of
      celiac disease-related antibodies in identifying celiac children. Moreover, the
      easy availability of human umbilical cord indicates that it would be proper to
      use this tissue as substrate, instead of monkey esophagus, for EmA search in the
      future.

PMID- 9161953
TI  - IgA endomysium antibodies on human umbilical cord: an excellent diagnostic tool
      for celiac disease in childhood.
AB  - BACKGROUND: An improvement in screening for celiac disease has recently been
      described that uses human umbilical cord as a substitute for monkey esophagus to
      determine IgA endomysium antibodies in adults. As using monkey esophagus is
      ethically questionable for large-scale screening, we studied whether substitution
      of umbilical cord would be suitable for pediatric patients as well. METHODS:
      Serum from 53 children with untreated celiac disease, 22 in remission and 13 on
      challenge, were screened for antigliadin IgA, antigliadin IgG, and IgA reticulin
      antibodies, in addition to IgA endomysium antibodies tested both on monkey
      esophagus and on human umbilical cord. Controls included 20 patients with cow
      milk-sensitive enteropathy, 23 with inflammatory bowel disease, and 23 with
      diabetes mellitus, and 48 patients who were biopsied to exclude celiac disease
      either because of positive gliadin antibody test or disturbed growth. RESULTS:
      Sensitivity (0.94) and specificity (1.0) were similar for umbilical cord and
      esophageal determinations in active celiac disease. Both substrates detected
      identical positive cases and neither gave false-positive results. In celiac
      patients on a gluten-free diet, endomysium antibodies with either substrate were
      positive in seven identical cases and negative in 15 of 22 cases. Correlations
      with reticulin antibodies were comparable with human umbilical cord and monkey
      esophagus (0.83 and 0.85, respectively; Spearman Correlation Section Pair-Wise
      deletion). CONCLUSIONS: Human umbilical cord is an excellent substitute for
      monkey esophagus to determine endomysium antibodies in celiac diagnosis in
      children and adolescents.

PMID- 9161954
TI  - In situ interleukin 5 gene expression in pediatric Crohn's disease.
AB  - BACKGROUND: Eosinophils contribute to the intestinal inflammatory infiltrate in
      Crohn's disease (CD). Eosinophilic infiltration occurs early in Crohn's
      recurrences, and a release of eosinophil cationic proteins has been observed in
      active CD. The proliferation, differentiation, and activation of eosinophils are
      highly dependent on the cytokine interleukin 5 (IL5). In the present study, we
      used in situ hybridization (ISH) to investigate the expression of the IL5 gene in
      intestinal specimens from patients with CD. METHODS: We studied 14 intestinal
      samples from eight children who had undergone ileocolectomy for advanced CD. The
      samples were examined for the intensity of the inflammatory infiltrate. Normal
      pediatric intestine specimens served as controls. In situ hybridization was
      performed on frozen tissue using radiolabeled IL5 mRNA probes. RESULTS: Positive
      signal with the IL5 antisense probe was observed within numerous cells
      infiltrating the specimens involved with CD. The number of IL5-expressing cells
      correlated with the histological grade of inflammation. Most of the labeled cells
      were eosinophils, characterized by their bilobed nuclei. Rare IL5-positive cells
      were detected in the control tissues. No positive signal was obtained with the
      IL5 sense probe. CONCLUSION: These results suggest that IL5 can be produced by
      eosinophils at the sites of inflammation in active CD and could be involved in
      the immune response by activating eosinophils, at least in part through an
      autocrine pathway, and perhaps by interacting with B and T cells.

PMID- 9161955
TI  - Bile acid therapy in pediatric hepatobiliary disease: the role of ursodeoxycholic
      acid.

PMID- 9161957
TI  - Sarcoidosis resulting in duodenal obstruction in an adolescent.

PMID- 9161956
TI  - Pseudomembranous colitis with Escherichia coli O157:H7.

PMID- 9161958
TI  - Liver disease in the Ashkenazi-Jewish lipoamide dehydrogenase deficiency.

PMID- 9161959
TI  - Esophageal intramural pseudodiverticulosis: a congenital or acquired condition?

PMID- 9161960
TI  - Cytomegalovirus colitis and immunotherapy.

PMID- 9161961
TI  - Secretory diarrhea caused by ipecac poisoning.

PMID- 9161962
TI  - A medical position statement of the North American Society for Pediatric
      Gastroenterology and Nutrition. Indications for pediatric esophageal manometry.

PMID- 9161963
TI  - Guidelines prepared by the ESPGAN Working Group on Acute Diarrhoea.
      Recommendations for feeding in childhood gastroenteritis. European Society of
      Pediatric Gastroenterology and Nutrition.

PMID- 9161964
TI  - Sucrose--how sweet is it?

PMID- 9161965
TI  - Enterohemorrhagic Escherichia coli O157:H7 infection and colitis in children.

PMID- 9161966
TI  - The highest incidence of celiac disease in Europe: the Swedish experience.

PMID- 9161967
TI  - Epidemiology of celiac disease in The Netherlands.

PMID- 9161968
TI  - Celiac disease in the general population: should we treat asymptomatic cases?

PMID- 9161969
TI  - From the neolithic revolution to gluten intolerance: benefits and problems
      associated with the cultivation of wheat.

PMID- 9161970
TI  - Celiac disease and malignancy: an immunological basis?

PMID- 9161971
TI  - Celiac disease and malignancy.

PMID- 9161972
TI  - Is celiac disease (gluten sensitivity) a premalignant disorder?

PMID- 9161973
TI  - Recombinant Ca2+ channels get O2 sensitive.

PMID- 9161974
TI  - Hypoxia inhibits the recombinant alpha 1C subunit of the human cardiac L-type
      Ca2+ channel.
AB  - 1. Whole-cell patch clamp recordings were used to investigate the effects of
      hypoxia on recombinant human L-type Ca2+ channel alpha 1C subunits stably
      expressed in human embryonic kidney (HEK 293) cells. 2. Ca2+ channel currents
      were reversibly inhibited by hypoxia (PO2 < 90 mmHg). The degree of inhibition
      depended on the charge carrier used, Ca2+ currents being more O2 sensitive than
      Ba2+ currents. 3. Hypoxic inhibition of Ca2+ channel currents was more pronounced
      at lower activating membrane potentials (< or = +30 mV), and was associated with
      a slowing of activation kinetics. Current inactivation and deactivation were
      unaffected by hypoxia. 4. Since hypoxia similarly regulates native L-type Ca2+
      channels in vascular smooth muscle cells, our results suggest that hypoxic
      regulation of L-type Ca2+ channels arises from modification of structural
      features of the alpha 1 subunit common to cardiac and smooth muscle L-type
      channels.

PMID- 9161975
TI  - Effects of lactate on the relative contribution of Ca2+ extrusion mechanisms to
      relaxation in guinea-pig ventricular myocytes.
AB  - 1. The aim of this study was to investigate the effects of 20 mM extracellular
      lactate on Ca2+ regulation mechanisms in enzymatically isolated single guinea-pig
      cardiac myocytes. 2. The activities of the Ca2+ regulation mechanisms during
      application of lactate were studied using rapid cooling contractures (RCCs) and
      fast application of caffeine. Cytoplasmic Ca2+ was monitored using the
      fluorescent indicator indo-1. 3. After application of 20 mM lactate for 5 min,
      the diastolic level of Ca2+ was increased. The change in cytoplasmic Ca2+
      elicited by stimulation (Ca2+ transient) was also changed. With lactate, the
      amplitude of the Ca2+ transient was smaller, and its time course was slower
      compared with control. 4. The recovery of cytoplasmic Ca2+ during rewarming after
      rapid cooling in lactate was slower than under control conditions. When the
      rewarming was performed either in Na(+)- and Ca(2+)-free solution or in the
      presence of 10 mM caffeine, the rate of recovery of cytoplasmic Ca2+ in lactate
      was slower than under control conditions, suggesting that the activity of both SR
      Ca2+ uptake and Na(+)-Ca2+ exchange is affected by lactate. 5. Cytoplasmic Ca2+
      recovery during application of 10 mM caffeine in lactate was slower than in the
      control. The rate of recovery of the caffeine-induced transient inward current
      was also slower supporting the hypothesis of a slower Ca2+ extrusion brought
      about by Na(+)-Ca2+ exchange. 6. The relative contribution of the Ca2+ extrusion
      mechanisms in the presence of lactate was investigated using paired RCCs. In
      lactate, a second RCC (RCC2) induced immediately after recovery from the first
      (RCC1) was greatly reduced compared with the control. RCC2/RCC1 x 100 in lactate
      was 39% and RCC2/RCC1 x 100 in control conditions was 60%, suggesting that the
      net sarcoplasmic reticulum Ca2+ uptake is smaller in the presence of lactate. 7.
      When Na(+)-free Ca2+ solution was used during the paired RCCs and rewarming,
      RCC2/RCC1 x 100 was increased to 96 and 95% in lactate and control conditions,
      respectively, implying that Ca2+ efflux from the cell can be maintained by the
      Na(+)-Ca2+ exchanger and that other Ca2+ removal mechanisms (mitochondria and
      sarcolemmal Ca(2+)-ATPase) remain largely unchanged in the presence of lactate.

PMID- 9161976
TI  - Ca(2+)-activated K+ channels in rat otic ganglion cells: role of Ca2+ entry via
      Ca2+ channels and nicotinic receptors.
AB  - 1. Intracellular recordings were made from neurones in the rat otic ganglion in
      vitro in order to investigate their morphological, physiological and synaptic
      properties. We took advantage of the simple structure of these cells to test for
      a possible role of calcium influx via nicotinic acetylcholine receptors during
      synaptic transmission. 2. Cells filled with biocytin comprised a homogeneous
      population with ovoid somata and sparse dendritic trees. Neurones had resting
      membrane potentials of -53 +/- 0.7 mV (n = 69), input resistances of 112 +/- 7 M
      omega, and membrane time constants of 14 +/- 0.9 ms (n = 60). Upon
      depolarization, all cells fired overshooting action potentials which were
      followed by an apamin-sensitive after-hyperpolarization (AHP). In response to a
      prolonged current injection, all neurones fired tonically. 3. The repolarization
      phase of action potentials had a calcium component which was mediated by N-type
      calcium channels. Application of omega-conotoxin abolished both the repolarizing
      hump and the after-hyperpolarization suggesting that calcium influx via N-type
      channels activates SK-type calcium-activated potassium channels which underlie
      the AHP. 4. The majority (70%) of neurones received innervation from a single
      preganglionic fibre which generated a suprathreshold excitatory postsynaptic
      potential mediated by nicotinic acetylcholine receptors. The other 30% of
      neurones also had one or more subthreshold nicotinic inputs. 5. Calcium influx
      via synaptic nicotinic receptors contributed to the AHP current, indicating that
      this calcium has access to the calcium-activated potassium channels and therefore
      plays a role in regulating cell excitability.

PMID- 9161977
TI  - Contrasting effects of intracellular redox couples on the regulation of maxi-K
      channels in isolated myocytes from rabbit pulmonary artery.
AB  - 1. The effects of intracellular redox couples were investigated on the activation
      by voltage, Ca2+ and NS 1619 of maxi-K channels in enzymatically isolated smooth
      muscle cells from large pulmonary arteries of rabbits. 2. In inside-out membrane
      patches, maxi-K channels were characterized by a single-channel conductance of
      266 pS in symmetrical 140 mM KCl solutions. The relationship between the open
      state probability (Po) and the membrane potential could be fitted to the
      Boltzmann equation. The activating action of intracellular Ca2+ was reversible,
      concentration dependent, and was manifested as the reduction in the voltage
      necessary to half-activate the channel (V1/2) with no change in the slope factor.
      NS 1619 also predisposed the maxi-K channel to open at more hyperpolarized
      membrane potentials. 3. The oxidizing agent 5,5'-dithio-bis(2-nitrobenzoic acid)
      (DTNB, 1 mM) activated maxi-K channels by inducing a negative shift of the
      activity-voltage curve, while the reducing agent 2-hydroxy-1-ethanethiol (beta
      mercaptoethanol) (BME, 1 mM) had no effect. DTNB increased the efficacy of Ca2+
      in activating maxi-K channels. The action of DTNB was not reversible upon wash
      out, but could be counteracted by BME. 4. Maxi-K channel activity was unaffected
      by other oxidizing agents, such as NAD (2 mM) and glutathione disulphide (GSSG, 5
      mM), or by their reduced forms (NADH and GSH). Mg-ATP (0.1 and 1 mM) increased
      the channel activity in a dose-dependent manner, while guanine nucleotides (100
      microM GTP gamma S, 500 microM GDP and 200 microM GDP beta S) had no effect. 5.
      Our data suggest that a change in the intracellular redox state, which would be
      expected during acute hypoxia, does not alter the activity of maxi-K channels of
      large pulmonary artery smooth muscle cells. The sulfhydryl-specific redox
      reagents (DTNB and BME) must act through another regulatory mechanism.

PMID- 9161978
TI  - Intracellular ATP activates inwardly rectifying K+ channels in human and monkey
      retinal Muller (glial) cells.
AB  - 1. In the vertebrate retina, the inwardly rectifying K+ (KIR) channels of the
      Muller (glial) cells are pathways for the redistribution of excess extracellular
      K+. Due to this role in K+ homeostasis, the activity of Muller cell KIR channels
      is likely to have significant functional consequences for the retina. In this
      study we asked whether intracellular ATP regulates the function of KIR channels
      expressed by Muller cells, the principal glia of the retina. 2. Freshly
      dissociated Muller cells from the human and monkey (Macaca fascicularis) retina
      were studied with various configurations of the patch-clamp technique. 3. Whole
      cell recordings from Muller cells revealed that a run-down of the inwardly
      rectifying K+ current (IK(IR)) was prevented if the pipette solution contained Mg
      ATP. Chemical ischaemia induced by inhibitors of glycolysis and oxidative
      phosphorylation caused a nearly 10-fold reduction in the IK(IR)) that was fully
      restored when metabolically inhibited Muller cells were internally perfused with
      ATP. 4. In recordings from membrane patches of fresh primate Muller cells, we
      found that inward-rectifying channels with a conductance of 20 pS in 100 mM Ko+
      were the predominant type of KIR channel. In excised patches these 20 pS KIR
      channels were activated when Mg-ATP was at the cytoplasmic surface. Experiments
      with inside-out patches indicated that the activity of the 20 pS KIR channels can
      be maintained by ATP synthesized at sites located close to the channel. 5. The
      inability of the non-hydrolysable ATP analogue 5'-adenylylimidodiphosphate (AMP
      PNP) to prevent the run-down of IK(IR))and the Mg2+ dependence of the ATP effect
      on KIR channels are consistent with a mechanism of activation requiring the
      hydrolysis of ATP. 6. These observations suggest that the metabolic state of a
      Muller cell regulates the activity of its 20 pS KIR channels and thus influences
      the function of the glial cell in maintaining K+ homeostasis in the retina.

PMID- 9161979
TI  - Two K(+)-selective conductances in single proximal tubule cells isolated from
      frog kidney are regulated by ATP.
AB  - 1. The whole-cell and single channel patch clamp techniques were used to identify
      K(+)-selective conductances in single proximal tubule cells isolated from frog
      kidney and to examine their ATP sensitivity. Whole-cell currents were inhibited
      by the K+ channel inhibitors Ba2+ and quinidine in a dose-dependent manner.
      Addition of Ba2+ alone, quinidine alone, or both inhibitors together revealed two
      separate conductances, one of which was blocked by both Ba2+ and quinidine
      (GBa)1, the other being sensitive to quinidine alone (Gquin). 2. With Na(+)
      containing Ringer solution in the bath and K(+)-containing Ringer solution in the
      pipette, both currents were selective for K+ over Na+. The K+ : Na+ selectivity
      ratio of GBa was around 50:1, while that of Gquin was 4:1. In symmetrical KCl
      solutions GBa showed inward rectification, while Gquin demonstrated outward
      rectification. 3. In the absence of pipette ATP, both GBa and Gquin ran down over
      10 min. However, when 2 mM ATP was included in the pipette GBa increased, while
      Gquin remained unchanged. 4. Single channel studies demonstrated that a
      basolateral K+ channel shared several of the characteristics of GBa. It was
      inhibited by both Ba2+ and quinidine, underwent run-down in excised patches in
      the absence of ATP, and was activated by ATP. 5. We conclude that cells of the
      frog proximal tubule contain at least two distinct K(+)-selective conductances,
      both of which are regulated by ATP, and which may be involved in pump-leak
      coupling.

PMID- 9161980
TI  - Acetylcholine-induced K+ currents in smooth muscle cells of intact rat small
      arteries.
AB  - 1. The mechanism of the sustained acetylcholine-induced endothelium-dependent
      hyperpolarization (EDH) in intact rat small mesenteric arteries prestimulated
      with noradrenaline (10(-6) M) was investigated by means of the single
      microelectrode voltage-clamp method. 2. The vascular smooth muscle cells (VSMCs)
      in this preparation are poorly or even not coupled for the reasons that: (1) the
      mean input resistance Rlnp of the clamped vascular smooth muscle increases from
      120 M omega under control conditions to 440 M omega after application of K+
      channel blocking drugs, (2) the voltage relaxation after injection of
      hyperpolarizing currents has a monoexponential time course and is linearly
      dependent on Rlnp, and (3) voltage steps induced by current-clamp steps are not
      transferred to locations in the vascular musculature 120 microns apart from the
      current injecting microelectrode. 3. Sustained (> 5 min) application of ACh (10(
      5) M) hyperpolarized the VSMCs by induction of a hyperpolarizing current. This
      effect was completely blocked by the inhibitor of the nitric oxide (NO) synthase
      L-NAME (10(-3) M) but not by the inhibitor of the soluble guanylate cyclase
      (sGCl) Methylene Blue (MB, 10(-4) M). 4. Application of the NO donor sodium
      nitroprusside (SNP, 10(-6) M) for more than 5 min mimicked the induction of the
      endothelium-dependent hyperpolarizing current in vessels with destroyed
      endothelium. The reversal potential of this current is dependent on the
      extracellular K+ concentration. The effect of SNP could also not be blocked by
      MB. 5. The blockers of ATP-dependent and Ca(2+)-dependent K+ channels,
      glibenclamide (Glb, 10(-5) M) and charybdotoxin (CTX, 5 x 10(-8) M),
      respectively, blocked a hyperpolarizing current in the VSMCs similar to the ACh-
      or SNP-induced current. 6. The isolated application of either Glb or CTX did not
      block the activation of the hyperpolarizing current by SNP. Only the combined
      administration of Glb and CTX blocked the SNP-induced current completely. 7. Our
      results suggest that in rat small mesenteric artery, ACh hyperpolarizes the VSMCs
      tonically by activating both ATP- and Ca(2+)-dependent K+ currents, only via
      release of NO from the endothelium without need for activation of the sGCl.

PMID- 9161981
TI  - Ionic mechanism of the effects of hydrogen peroxide in rat ventricular myocytes.
AB  - 1. Whole-cell and amphotericin-perforated patch-clamp techniques have been used
      to study the effects of hydrogen peroxide (H2O2) on action potentials and
      underlying ionic currents in single myocytes from the ventricles of adult rat
      hearts. 2. The results obtained differed markedly depending on the recording
      method utilized. Conventional whole-cell recordings, in which the myoplasm is
      dialysed with the contents of the pipette, failed to show any significant effects
      of H2O2 on the action potential or cell shortening. In contrast, when action
      potentials were recorded with the amphotericin-perforated patch method, H2O2 (50
      200 microM) produced a marked prolongation of the action potential and an
      increase in cell shortening. 3. Voltage-clamp recordings with the amphotericin
      perforated patch method showed that H2O2 caused no significant changes in either
      the Ca(2+)-independent transient outward K+ current (Ito) or the inwardly
      rectifying K+ current (IK1). 4. Application of tetrodotoxin (TTX; 8 x 10(-6) M),
      a Na+ channel blocker, largely inhibited the effects of H2O2 on the action
      potential. Moreover, anthopleurin A (4 x 10 (-7) M), which augments Na+ current
      (INa) by slowing its inactivation, mimicked the effects of H2O2 on the action
      potential of ventricular myocytes. These effects on INa were also blocked almost
      completely by TTX. 5. The hypothesis that H2O2 can augment INa by slowing its
      kinetics of inactivation was tested directly using ensemble recordings from cell
      attached macropatches. These results demonstrated a significant enhancement of
      late opening events when H2O2 (200 microM) was included in the recording pipette.
      A corresponding slowing of inactivation of the ensemble INa was observed. 6. The
      possibility that protein kinase C (PKC) is an intracellular second messenger for
      the observed effects of H2O2 was examined using the blocker bisindolylmaelimide
      (BIS; 10(-7) M). Bath application of BIS prior to H2O2 exposure significantly
      delayed and also attenuated the development of the action potential prolongation.
      7. These results demonstrate marked electrophysiological effects of H2O2 in rat
      ventricle. The dependence of these effects on recording methods suggests
      involvement of an intracellular second messenger, and the results with the PKC
      inhibitor, BIS, support this possibility. The most prominent effect of H2O2 on
      the ionic currents which underlie the action potential is a slowing of
      inactivation of the TTX-sensitive INa. Recent molecular studies have demonstrated
      a PKC phosphorylation site on the rat cardiac Na+ channel isoform and have also
      shown that PKC activation can slow inactivation of INa.

PMID- 9161982
TI  - Differential control of the hyperpolarization-activated current (i(f)) by cAMP
      gating and phosphatase inhibition in rabbit sino-atrial node myocytes.
AB  - 1. The actions of the phosphatase inhibitor calyculin A on the hyperpolarization
      activated cardiac 'pacemaker' current (i(f)) were determined in single cells
      isolated from the sino-atrial (SA) node of the rabbit. 2. Cells were incubated
      for 8 min in Tyrode solution containing calyculin A (0.5 microM) and then
      superfused with normal Tyrode solution. The mean normalized i(f) measured in
      eight cells at mid-activation voltages during and after exposure to calyculin A
      increased maximally by 47% with a time constant of 466 s, a time much longer than
      that required for cAMP-mediated i(f) stimulation (about 8 s). 3. In two-pulse
      protocols, calyculin A treatment increased i(f) at full as well as at mid
      activation voltages, indicating a higher i(f) conductance. 4. Measurement of the
      conductance-voltage (gf(V)) relation by voltage ramp protocols confirmed a
      conductance increase by calyculin A, with no significant change in the position
      of the activation curve on the voltage axis. Data pooled together from ramp and
      two-pulse protocols yielded a calyculin A-induced increase in fully activated
      i(f) conductance of 39.6 +/- 6.4% (n = 16 cells). 5. The positive and negative
      shift of i(f) voltage dependence in response to beta-adrenergic (1 microM
      isoprenaline) and muscarinic stimulation (1 microM acetylcholine), respectively,
      was preserved after the calyculin A-induced increase in conductance. The shift of
      the i(f) activation curve induced by 1 microM isoprenaline was significantly
      larger in calyculin A-treated cells (8.8 vs. 5.8 mV). 6. These data indicate that
      phosphatase inhibition increases i(f) in a manner distinct from the direct cAMP
      pathway and potentiates the beta-adrenergic-mediated i(f) modulation.

PMID- 9161983
TI  - Novel activation stimulus of chloride channels by potassium in human osteoblasts
      and human leukaemic T lymphocytes.
AB  - 1. The whole-cell recording mode of the patch-clamp technique was used to study
      the effect of extracellular K+ and Rb+ on membrane currents in human osteoblasts,
      in a human osteoblast-like cell line, and in the Jurkat human leukaemic T cell
      line. 2. Increasing the extracellular concentration of K+ increased the membrane
      conductance of the cells in a concentration-dependent manner. This increase in
      membrane conductance was due to the activation of a Cl- conductance. Rb+ also
      induced this conductance, but conductance was less than half that seen in K+. 3.
      The Cl- channel blockers 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid
      (DIDS) and 4-acetamido-4'-isothiocyanatostilbene 2,2'-disulphonic acid (SITS)
      blocked the K(+)-induced Cl- current in a voltage-dependent manner. The degree of
      blockade increased with membrane depolarization to a maximum level at 40 mV. At
      potentials above this value the block appeared to decrease. 4. Both tonicity and
      K+ were required for maximal activation of the Cl- conductance since the K(+)
      induced Cl- conductance could be inhibited by hypertonic solutions and the
      activation of a volume-sensitive Cl- conductance by hypotonic solutions could be
      enhanced by extracellular K+. 5. We conclude that an outwardly rectifying Cl-
      conductance can be activated either upon osmotic swelling or by an increase in
      extracellular K+. Both activation pathways may be involved in cell volume
      regulation and seem to apply to volume-sensitive Cl- channels in general since we
      observe this phenomenon in two different cell types, in human osteoblasts as well
      as in human leukaemic T lymphocytes.

PMID- 9161984
TI  - Human body-segment tilts induced by galvanic stimulation: a vestibularly driven
      balance protection mechanism.
AB  - 1. We have studied the effects of changes in posture on the motor response to
      galvanic vestibular stimulation (GVS). The purpose of the experiments was to
      investigate whether the function of the GVS-evoked response is to stabilize the
      body or the head in space. Subjects faced forwards with eyes closed standing with
      various stance widths and sitting. In all cases the GVS-evoked response consisted
      of a sway of the body towards the anodal ear. 2. In the first set of experiments
      the response was measured from changes in (i) electromyographic activity of hip
      and ankle muscles, (ii) the lateral ground reaction force, and (iii) lateral
      motion of the body at the level of the neck (C7). For all measurements the
      response became smaller as the feet were placed further apart. 3. In the second
      set of experiments we measured the GVS-evoked tilts of the head, torso and
      pelvis. The basic response consisted of a tilt in space (anodal ear down) of all
      three segments. The head tilted more than the trunk and the trunk tilted more
      than the pelvis producing a leaning and bending of the body towards the anodal
      ear. This change in posture was sustained for the duration of the stimulus. 4.
      The tilt of all three segments was reduced by increasing the stance width. This
      was due to a reduction in evoked tilt of the pelvis, the bending of the upper
      body remaining relatively unchanged. Changing from a standing to a sitting
      posture produced additional reductions in tilt by reducing the degree of upper
      body bending. 5. The results indicate that the response is organized to stabilize
      the body rather than the head in space. We suggest that GVS produces a vestibular
      input akin to that experienced on an inclined support surface and that the
      function of the response is to counter any threat to balance by keeping the
      centre of mass of the body within safe limits.

PMID- 9161985
TI  - Run-down of the GABAA response under experimental ischaemia in acutely
      dissociated CA1 pyramidal neurones of the rat.
AB  - 1. The effect of experimental ischaemia on the response to gamma-aminobutyric
      acid (GABA) was assessed in acutely dissociated CA1 pyramidal neurones of rats,
      using the patch-clamp technique. 2. Rapid application of 3 x 10(-5) M GABA
      induced a bicuculline-sensitive inward Cl- current (IGABA) at a holding potential
      (Vh) of -44 mV. The peak amplitude of IGABA showed a time-dependent decrease (run
      down) when it was recorded with the conventional whole-cell mode without internal
      ATP. The run-down was not observed when the intracellular ATP concentration
      ([ATP]i) was maintained by the nystatin-perforated recording with an
      intracellular Na+ concentration ([Na+]i) of 0 mM. 3. When [Na+]i was increased to
      more than 30 mM, the IGABA run-down was observed even with the nystatin
      perforated recording. 4. The IGABA run-down observed at 60 mM [Na+]i with the
      nystatin method was further enhanced under experimental ischaemia without changes
      in the reversal potential of IGABA. The enhanced run-down was suppressed by
      application of the Na+,K(+)-ATPase inhibitors, ouabain and SPAI-1. 5. IGABA run
      down during ischaemia was also accompanied by an outward holding current and a
      concomitant increase in intracellular free Ca2+ concentration ([Ca2+]i) in 48.5%
      of the neurones. The outward current was a Ca(2+)-activated K+ current, which was
      blocked by 3 x 10(-7) M charybdotoxin. 6. In the inside-out mode of the single
      channel analysis, GABA activated three subconductance states with conductances of
      33.4, 22.7 and 15.2 pS. Reduction of ATP concentration from 2 to 0 mM on the
      intracellular side suppressed the channel activities, while an increase in Ca2+
      concentration from 0.7 x 10(-9) to 1.1 x 10(-6) M had no effect. 7. These results
      suggest that ischaemia induces the run-down of the postsynaptic GABA response at
      the GABAA receptor level, and that this run-down is triggered by a decrease in
      [ATP]i.

PMID- 9161986
TI  - Effect, number and location of synapses made by single pyramidal cells onto
      aspiny interneurones of cat visual cortex.
AB  - 1. Dual intracellular recordings were made from synaptically coupled pyramidal
      cell-to-interneurone pairs (n = 5) of the cat visual cortex in vitro. Pre- and
      postsynaptic neurones were labelled with biocytin, followed by correlated light
      and electron microscopic analysis to determine all sites of synaptic interaction.
      2. Pyramidal neurones in layers II-III elicited monosynaptic EPSPs in three
      distinct classes of smooth dendritic local-circuit neurones, namely basket cells
      (n = 3), a dendrite-targeting cell (n = 1) and a double bouquet cell (n = 1).
      Unitary EPSPs in basket cells were mediated by one, two, and two synaptic
      junctions, whereas the pyramid-to-dendrite-targeting cell and pyramid-to-double
      bouquet cell interaction were mediated by five and seven synaptic junctions,
      respectively. Recurrent synaptic junctions were found on all somato-dendritic
      compartments, with a tendency to be clustered close to the soma on the double
      bouquet and dendrite-targeting cells. The latter interneurones were reciprocally
      connected with pyramidal cells. 3. Unitary EPSPs had an average peak amplitude of
      1005 +/- 518 microV, fast rise times (10-90%; 0.67 +/- 0.25 ms) and were of short
      duration (at half-amplitude, 4.7 +/- 1.0 ms). Their decay was monoexponential
      (tau = 7.8 +/- 4.3 ms) at hyperpolarized membrane potentials and appeared to be
      shaped by passive membrane properties (tau = 9.2 +/- 8.5 ms). All parameters of
      concomitantly recorded spontaneous EPSPs were remarkably similar (mean amplitude,
      981 +/- 433 microV; mean rise time, 0.68 +/- 0.18 ms; mean duration, 4.7 +/- 1.7
      ms). 4. In all three pyramidal-to-basket cell pairs, closely timed (10-50 ms)
      pairs of presynaptic action potentials resulted in statistically significant
      paired-pulse depression, the mean of the averaged second EPSPs being 80 +/- 11%
      of the averaged conditioning event. The overall degree of paired-pulse modulation
      was relatively little affected by either the amplitude of the preceding event or
      the inter-event interval. 5. The probability density function of the peak
      amplitudes of the unitary EPSPs could be adequately fitted with a quantal model.
      Without quantal variance, however, the minimum number of components in the model,
      excluding the failures, exceeded the number of electron microscopically
      determined synaptic junctions for all five connections. In contrast,
      incorporating quantal variance gave a minimum number of components which was
      compatible with the number of synaptic junctions, and which fitted the data
      equally well as models incorporating additional components but no quantal
      variance. For this model with quantal variance with the minimum number of
      components the estimate of the quantal coefficient of variation ranged between
      0.33 and 0.46, and the corresponding quantal sizes ranged between 260 and 657
      microV. The peak EPSP amplitudes in two of the four connections with more than
      one synaptic junction could be adequately described by a uniform binomial model
      for transmitter release. 6. In conclusion, at least three distinct interneurone
      classes receive local excitatory pyramidal cell input which they relay to
      different compartments on their postsynaptic target neurones. The reliability of
      transmission is high, but the fast time course of the EPSPs constrains their
      temporal summation. Due to the relatively small amplitude of unitary EPSPs
      several convergent inputs will therefore be required to elicit suprathreshold
      responses.

PMID- 9161987
TI  - Fast IPSPs elicited via multiple synaptic release sites by different types of
      GABAergic neurone in the cat visual cortex.
AB  - 1. The effects of synapses established by smooth dendritic neurones on pyramidal
      and spiny stellate cells were studied in areas 17 and 18 of the cat visual cortex
      in vitro. Paired intracellular recordings with biocytin-filled electrodes and
      subsequent light and electron microscopic analysis were used to determine the
      sites of synaptic interaction. 2. All smooth dendritic cells established type II
      synapses previously shown to be made by terminals containing GABA, therefore the
      studied cells are probably GABAergic. Three classes of presynaptic cell could be
      defined, based on their efferent synaptic target preference determined from
      random samples of unlabelled postsynaptic cells. (a) Basket cells (n = 6)
      innervated mainly somata (49.9 +/- 13.8%) and dendritic shafts (45.2 +/- 10.7%)
      and, to a lesser extent, dendritic spines (4.9 +/- 4.6%). (b) Dendrite-targeting
      cells (n = 5) established synapses predominantly on dendritic shafts (84.3 +/-
      9.4%) and less frequently on dendritic spines (11.2 +/- 6.7%) or somata (4.5 +/-
      4.7%). (c) Double bouquet cells (n = 4) preferred dendritic spines (69.2 +/-
      4.2%) to dendritic shafts (30.8 +/- 4.2%) as postsynaptic targets and avoided
      somata. 3. Interneurones formed 5240 +/- 1600 (range, 2830-9690) synaptic
      junctions in the slices. Based on the density of synapses made by single
      interneurones and the volume density of GABAergic synapses, it was calculated
      that an average interneurone provides 0.66 +/- 0.20% of the GABAergic synapses in
      its axonal field. 4. The location of synaptic junctions on individual, identified
      postsynaptic cells reflected the overall postsynaptic target distribution of the
      same GABAergic neurone. The number of synaptic junctions between pairs of
      neurones could not be predicted from light microscopic examination. The number of
      electron microscopically verified synaptic sites was generally smaller for the
      dendritic domain and larger for the somatic domain than expected from light
      microscopy. All presynaptic cells established multiple synaptic junctions on
      their postsynaptic target cells. A basket cell innervated a pyramidal cell via
      fifteen release sites; the numbers of synapses formed by three dendrite-targeting
      cells on pyramidal cells were seventeen and eight respectively, and three on a
      spiny stellate cell; the interaction between a double bouquet cell and a
      postsynaptic pyramidal cell was mediated by ten synaptic junctions. 5. All three
      types of interneurone (n = 6; 2 for each type of cell) elicited short-latency
      IPSPs with fast rise time (10-90%; 2.59 +/- 1.02 ms) and short duration (at half
      amplitude, 15.82 +/- 5.24 ms), similar to those mediated by GABAA receptors. 6.
      Average amplitudes of unitary IPSPs (n = 6) were 845 +/- 796 microV (range, 134
      2265 microV). Variability of IPSP amplitude was moderate, the average ratio of
      IPSP and baseline noise variance was 1.54 +/- 0.96. High frequency activation of
      single presynaptic dendrite-targeting cells led to an initial summation followed
      by use-dependent depression of the averaged postsynaptic response. Double bouquet
      cell-evoked IPSPs, recorded in the soma, had a smaller amplitude than those
      evoked by the other two cell types. In all connections, transmission failures
      were rare or absent, particularly when mediated by a high number of release
      sites. 7. The results demonstrate that different types of neocortical GABAergic
      neurones innervate distinct domains on the surface of their postsynaptic target
      cells. Nevertheless, all three types of cell studied here elicit fast IPSPs and
      provide GABAergic input through multiple synaptic release sites with few, if any,
      failures of transmission.

PMID- 9161988
TI  - GABAB receptor-mediated inhibition of spontaneous inhibitory synaptic currents in
      rat midbrain culture.
AB  - 1. Tight-seal, whole-cell recording was used to study GABAB receptor-mediated
      inhibition of spontaneous inhibitory synaptic currents in cultured rat midbrain
      neurones. 2. Spontaneous miniature inhibitory postsynaptic currents (mIPSCs) were
      recorded in tetrodotoxin (TTX), Cd2+ and Ba2+. (R)-(-)-baclofen reduced the
      frequency of mIPSCs through a presynaptic mechanism. The EC50 for this effect was
      7 microM. It was antagonized by the GABAB receptor antagonist CGP55845A (0.5
      microM). 3. In pertussis toxin (PTX)-treated cultures, some GABAB receptor
      mediated reduction of the frequency of mIPSCs persisted. In contrast, PTX
      treatment totally abolished inhibition of miniature excitatory postsynaptic
      currents (mEPSCs). 4. In PTX-treated cultures, a saturating concentration of (R)
      (-)-baclofen inhibited action potential-generated IPSCs but no EPSCs. 5. PTX
      treatment abolished the (R)-(-)-baclofen-mediated inhibition of high voltage
      activated somatic Ca2+ currents and of spontaneous IPSCs depending on presynaptic
      Ca2+ entry. 6. We conclude that cellular mechanisms underlying GABAB receptor
      mediated inhibition of mIPSCs contribute to auto-inhibition of GABA release.

PMID- 9161989
TI  - Synaptic origin and stimulus dependency of neuronal oscillatory activity in the
      primary visual cortex of the cat.
AB  - 1. We have studied the oscillatory activity of single neurons (91 recorded
      extracellularly and 76 intracellularly) in the primary visual cortex of cats and
      kittens to characterize its origins and its stimulus dependency. A new method for
      the detection of oscillations was developed in order to maximize the range of
      detectable frequencies in both types of recordings. Three types of activity were
      examined: spontaneous background activity, responses to intracellular current
      steps and visual responses. 2. During spontaneous activity, persistent
      oscillatory activity was very rare in both types of recordings. However, when
      intracellular records were made using KCl-filled micropipettes, spontaneous
      activity appeared rhythmic and contained repeated depolarizing events at a
      variety of frequencies, suggestive of tonic periodic inhibitory input normally
      masked at resting potential. 3. Patterns of firing activity in response to
      intracellular current steps allowed us to classify neurons as regular spiking,
      intrinsically bursting, and fast-spiking types, as described in vitro. In the
      case of rhythmically firing cells, the spike frequency increased with the amount
      of injected current. Subthreshold current-induced oscillations were rarely
      observed (2 out of 76 cells). 4. Visual stimulation elicited oscillations in one
      third of the neurons (55 out of 167), predominantly in the 7-20 Hz frequency
      range in 93% of the cases. Rhythmicity was observed in both simple and complex
      cells, and appeared to be more prominent at 5 and 6 weeks of age. 5.
      Intracellular recordings in bridge mode and voltage clamp revealed that visually
      evoked oscillations were driven by synaptic activity and did not depend primarily
      on the intrinsic properties of recorded neurons. Hyperpolarizing the membrane led
      to an increase in the size of the rhythmic depolarizing events without a change
      in frequency. In voltage-clamped cells, current responses showed large
      oscillations at the same frequency as in bridge mode, independently of the actual
      value of the holding potential. 6. In fourteen intracellularly recorded neurons,
      oscillations consisted of excitatory events that could be superimposed on a
      depolarizing or a hyperpolarizing slow wave. In two other neurons, visual
      responses consisted of excitatory and inhibitory events, alternating with a
      constant phase shift. 7. Drifting bars were much more efficient in evoking
      oscillatory responses than flashed bars. Except in three cells, the frequency of
      the oscillation did not depend on the physical characteristics of the stimulus
      that were tested (contrast, orientation, direction, ocularity and position in the
      receptive field). No significant correlation was found between the intensity of
      the visual response and the strength of the rhythmic component. 8. Although it
      cannot be excluded that the dominant frequency of oscillations might be related
      to the type of anaesthetics used, no correlation was found between local EEG and
      the oscillatory activity elicited by visual stimulation. 9. We conclude that the
      oscillations observed in the present work are generated by synaptic activity. It
      is likely that they represent an important mode of transmission in sensory
      processing, resulting from periodic packets of synchronized activity propagated
      across recurrent circuits. Their relevance to perceptual binding is further
      discussed.

PMID- 9161991
TI  - Integrated phrenic responses to carotid afferent stimulation in adult rats
      following perinatal hyperoxia.
AB  - 1. Hypoxic ventilatory responses are greatly attenuated in adult rats exposed to
      moderate hyperoxia (60% O2) during the first month of life (perinatal treated
      rats). The present study was designed to test the hypothesis that perinatal
      hyperoxia impairs central integration of carotid chemoreceptor afferent inputs,
      thereby diminishing the hypoxic ventilatory response. 2. Time-dependent phrenic
      nerve responses to electrical stimulation of the carotid sinus nerve (CSN) and
      steady-state relationships between CSN stimulation frequency and phrenic nerve
      output were compared in control and perinatal treated rats. The rats were
      urethane anaesthetized, vagotomized, paralysed and artificially ventilated. End
      tidal CO2 was monitored and maintained at isocapnic levels; arterial blood gases
      were determined. 3. Two stimulation protocols were used: (1) three 2 min episodes
      of CSN stimulation (20 Hz, 0.2 ms duration, 3 x threshold), separated by 5 min
      intervals; and (2) nine 45 s episodes of CSN stimulation with stimulus
      frequencies ranging from 0.5 to 20 Hz (0.2 ms duration, 3 x threshold), separated
      by 4 min intervals. 4. The mean threshold currents to elicit phrenic responses
      were similar between groups. Burst frequency (f, burst min-1), peak amplitude of
      integrated phrenic activity (integral of Phr), and minute phrenic activity
      (integral of Phr x f) during and after CSN stimulation were not distinguishable
      between groups in either protocol at any time or at any stimulus intensity (P >
      0.05). 5. Perinatal hyperoxia does not alter temporal or steady-state phrenic
      responses to CSN stimulation, suggesting that the central integration of carotid
      chemoreceptor afferent inputs is not impaired in perinatal treated rats. It is
      speculated that carotid chemoreceptors per se are impaired in perinatal treated
      rats.

PMID- 9161990
TI  - Functional improvement of damaged adult mouse muscle by implantation of primary
      myoblasts.
AB  - 1. Myoblasts from expanded primary cultures were implanted into cryodamaged
      soleus muscles of adult BALB/c mice. One to four months later isometric tension
      recordings were performed in vitro, and the male donor cells implanted into
      female hosts were traced on histological sections using a Y-chromosome-specific
      probe. The muscles were either mildly or severely cryodamaged, which led to
      reductions in tetanic muscle force to 33% (n = 9 muscles, 9 animals) and 70% (n =
      11) of normal, respectively. Reduced forces resulted from deficits in
      regeneration of muscle tissue as judged from the reduced desmin-positive cross
      sectional areas (34 and 66% of control, respectively). 2. Implantation of 10(6)
      myogenic cells into severely cryodamaged muscles more than doubled muscle tetanic
      force (to 70% of normal, n = 14), as well as specific force (to 66% of normal).
      Absolute and relative amount of desmin-positive muscle cross-sectional areas were
      significantly increased indicating improved microarchitecture and less fibrosis.
      Newly formed muscle tissue was fully innervated since the tetanic forces
      resulting from direct and indirect (nerve-evoked) stimulation were equal.
      Endplates were found on numerous Y-positive muscle fibres. 3. As judged from
      their position under basal laminae of muscle fibres and the expression of M
      cadherin, donor-derived cells contributed to the pool of satellite cells on small
      and large-diameter muscle fibres. 4. Myoblast implantation after mild cryodamage
      and in undamaged muscles had little or no functional or structural effects; in
      both preparations only a few Y-positive muscle nuclei were detected. It is
      concluded that myoblasts from expanded primary cultures-unlike permanent cell
      lines-significantly contribute to muscle regeneration only when previous muscle
      damage is extensive and loss of host satellite cells is severe.

PMID- 9161994
TI  - Nucleosynthesis in stars: recent developments.
AB  - The development of new observational, experimental, and computational
      technologies is changing our understanding of the origins of the elements by
      thermonuclear burning in stars. Gamma-ray lines from newly made radioactive
      nuclei have been identified using instruments onboard low-Earth orbiting
      satellites. Grains in meteorites have isotopic anomalies which suggest that the
      grains were put together in a stellar explosion such as a supernova. Computer
      simulations allow such anomalies to be used to probe how these events happen. The
      simulations are being independently tested by experiments with high-energy
      density lasers. These developments are beginning to provide a quantitative
      diagnostic of galactic evolution, and of the epoch of formation of the first
      stars and galaxies.

PMID- 9161999
TI  - Planetary nebulae: understanding the physical and chemical evolution of dying
      stars.
AB  - Planetary nebulae are one of the few classes of celestial objects that are active
      in every part of the electromagnetic spectrum. These fluorescing and often dusty
      expanding gaseous envelopes were recently found to be quite complex in their
      dynamics and morphology, but refined theoretical models can account for these
      discoveries. Great progress was also made in understanding the mechanisms that
      shape the nebulae and the spectra of their central stars. In addition,
      applications for planetary nebulae have been worked out; for example, they have
      been used as standard candles for long-range distances and as tracers of the
      enigmatic dark matter.

PMID- 9162001
TI  - A hominid from the lower Pleistocene of Atapuerca, Spain: possible ancestor to
      Neandertals and modern humans.
AB  - Human fossil remains recovered from the TD6 level (Aurora stratum) of the lower
      Pleistocene cave site of Gran Dolina, Sierra de Atapuerca, Spain, exhibit a
      unique combination of cranial, mandibular, and dental traits and are suggested as
      a new species of Homo-H. antecessor sp. nov. The fully modern midfacial
      morphology of the fossils antedates other evidence of this feature by about 650,
      000 years. The midfacial and subnasal morphology of modern humans may be a
      retention of a juvenile pattern that was not yet present in H. ergaster. Homo
      antecessor may represent the last common ancestor for Neandertals and modern
      humans.

PMID- 9162005
TI  - Control of mouse cardiac morphogenesis and myogenesis by transcription factor
      MEF2C.
AB  - Members of the myocyte enhancer factor-2 (MEF2) family of MADS (MCM1, agamous,
      deficiens, serum response factor)-box transcription factors bind an A-T-rich DNA
      sequence associated with muscle-specific genes. The murine MEF2C gene is
      expressed in heart precursor cells before formation of the linear heart tube. In
      mice homozygous for a null mutation of MEF2C, the heart tube did not undergo
      looping morphogenesis, the future right ventricle did not form, and a subset of
      cardiac muscle genes was not expressed. The absence of the right ventricular
      region of the mutant heart correlated with down-regulation of the dHAND gene,
      which encodes a basic helix-loop-helix transcription factor required for cardiac
      morphogenesis. Thus, MEF2C is an essential regulator of cardiac myogenesis and
      right ventricular development.

PMID- 9162006
TI  - Severe fibronectin-deposit renal glomerular disease in mice lacking uteroglobin.
AB  - Despite myriads of biological activities ascribed to uteroglobin (UG), a steroid
      inducible secreted protein, its physiological functions are unknown. Mice in
      which the uteroglobin gene was disrupted had severe renal disease that was
      associated with massive glomerular deposition of predominantly multimeric
      fibronectin (Fn). The molecular mechanism that normally prevents Fn deposition
      appears to involve high-affinity binding of UG with Fn to form Fn-UG heteromers
      that counteract Fn self-aggregation, which is required for abnormal tissue
      deposition. Thus, UG is essential for maintaining normal renal function in mice,
      which raises the possibility that an analogous pathogenic mechanism may underlie
      genetic Fn-deposit human glomerular disease.

PMID- 9162007
TI  - A cellular cofactor for the constitutive transport element of type D retrovirus.
AB  - A human nuclear protein that specifically interacts with the constitutive
      transport element (CTE) of simian retrovirus was identified as adenosine 5'
      triphosphate-dependent RNA helicase A. This protein could bind to functional CTE
      but not to inactive CTE mutants. The interaction of helicase A with CTE was
      distinct from previously described helicase activity of this protein. Helicase A
      shuttled from the nucleus to the cytoplasm in the presence of a transcription
      inhibitor or in cells transiently overexpressing CTE-containing RNA. In vivo
      colocalization of helicase A and CTE was observed in experiments that combined in
      situ hybridization and immunostaining. These results suggest that helicase A
      plays a role in the nuclear export of CTE-containing RNA.

PMID- 9162009
TI  - STAT3 as an adapter to couple phosphatidylinositol 3-kinase to the IFNAR1 chain
      of the type I interferon receptor.
AB  - STAT (signal transducers and activators of transcription) proteins undergo
      cytokine-dependent phosphorylation on serine and tyrosine. STAT3, a transcription
      factor for acute phase response genes, was found to act as an adapter molecule in
      signal transduction from the type I interferon receptor. STAT3 bound to a
      conserved sequence in the cytoplasmic tail of the IFNAR1 chain of the receptor
      and underwent interferon-dependent tyrosine phosphorylation. The p85 regulatory
      subunit of phosphatidylinositol 3-kinase, which activates a series of serine
      kinases, bound to phosphorylated STAT3 and subsequently underwent tyrosine
      phosphorylation. Thus, STAT3 acts as an adapter to couple another signaling
      pathway to the interferon receptor.

PMID- 9162010
TI  - Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis.
AB  - The dominant exported proteins and protective antigens of Mycobacterium
      tuberculosis are a triad of related gene products called the antigen 85 (Ag85)
      complex. Each has also been implicated in disease pathogenesis through its
      fibronectin-binding capacities. A carboxylesterase domain was found within the
      amino acid sequences of Ag85A, B, and C, and each protein acted as a
      mycolyltransferase involved in the final stages of mycobacterial cell wall
      assembly, as shown by direct enzyme assay and site-directed mutagenesis.
      Furthermore, the use of an antagonist (6-azido-6-deoxy-alpha, alpha'-trehalose)
      of this activity demonstrates that these proteins are essential and potential
      targets for new antimycobacterial drugs.

PMID- 9162011
TI  - Hyperplasia of lymphatic vessels in VEGF-C transgenic mice.
AB  - No growth factors specific for the lymphatic vascular system have yet been
      described. Vascular endothelial growth factor (VEGF) regulates vascular
      permeability and angiogenesis, but does not promote lymphangiogenesis.
      Overexpression of VEGF-C, a ligand of the VEGF receptors VEGFR-3 and VEGFR-2, in
      the skin of transgenic mice resulted in lymphatic, but not vascular, endothelial
      proliferation and vessel enlargement. Thus, VEGF-C induces selective hyperplasia
      of the lymphatic vasculature, which is involved in the draining of interstitial
      fluid and in immune function, inflammation, and tumor metastasis. VEGF-C may play
      a role in disorders involving the lymphatic system and may be of potential use in
      therapeutic lymphangiogenesis.

PMID- 9162012
TI  - Geometric control of cell life and death.
AB  - Human and bovine capillary endothelial cells were switched from growth to
      apoptosis by using micropatterned substrates that contained extracellular matrix
      coated adhesive islands of decreasing size to progressively restrict cell
      extension. Cell spreading also was varied while maintaining the total cell-matrix
      contact area constant by changing the spacing between multiple focal adhesion
      sized islands. Cell shape was found to govern whether individual cells grow or
      die, regardless of the type of matrix protein or antibody to integrin used to
      mediate adhesion. Local geometric control of cell growth and viability may
      therefore represent a fundamental mechanism for developmental regulation within
      the tissue microenvironment.

PMID- 9162013
TI  - Lamina-specific connectivity in the brain: regulation by N-cadherin,
      neurotrophins, and glycoconjugates.
AB  - In the vertebrate brain, neurons grouped in parallel laminae receive distinct
      sets of synaptic inputs. In the avian optic tectum, arbors and synapses of most
      retinal axons are confined to 3 of 15 laminae. The adhesion molecule N-cadherin
      and cell surface glycoconjugates recognized by a plant lectin are selectively
      associated with these "retinorecipient" laminae. The lectin and a monoclonal
      antibody to N-cadherin perturbed laminar selectivity in distinct fashions. In
      contrast, neurotrophins increased the complexity of retinal arbors without
      affecting their laminar distribution. Thus, cell surface molecules and soluble
      trophic factors may collaborate to shape lamina-specific arbors in the brain,
      with the former predominantly affecting their position and the latter their size.

PMID- 9162015
TI  - Preferential modification of nuclear proteins by a novel ubiquitin-like molecule.
AB  - Sentrin is a novel ubiquitin-like protein that protects cells against both anti
      Fas and tumor necrosis factor-induced cell death. Antiserum recognizing the N
      terminus of sentrin revealed the presence of a 18-kDa sentrin monomer, a 90-kDa
      band (p90), and multiple high molecular mass bands. Because sentrin possesses the
      conserved Gly-Gly residues near the C terminus, it is likely that these
      additional bands represent conjugation of sentrin to other proteins in a manner
      that is similar to the ubiquitination pathway. Transient expression of
      hemagglutinin epitope-tagged sentrin mutants in COS cells demonstrated that the
      sentrin C terminus is cleaved, which allows it to be conjugated to other proteins
      via the conserved C-terminal Gly residue. Immunocytochemical staining and cell
      fractionation analysis demonstrated that sentrin monomer is localized
      predominantly to the cytosol. However, p90 and the majority of sentrinized
      proteins appeared to be localized to the nucleus. When the conserved Gly-Gly
      residues of sentrin were changed to Gly-Ala, only sentrin monomer and p90 but not
      the high molecular mass bands were observed. Thus, p90 generation appears to be
      required for the formation of high molecular mass bands in the nucleus. Taken
      together, sentrinization represents a novel pathway for nuclear protein
      modification, which is distinct from ubiquitination.

PMID- 9162016
TI  - Finkel-Biskis-Reilly mouse osteosarcoma virus v-fos inhibits the cellular
      response to ionizing radiation in a myristoylation-dependent manner.
AB  - DNA damage is recognized as a central component of carcinogenesis. DNA-damaging
      agents activate a number of signal transduction pathways that lead to repair of
      the DNA, apoptosis, or cell cycle arrest. It is reasoned that a cell deficient in
      DNA repair is more likely to acquire other cancer-promoting mutations. Despite
      the recent interest in the link between DNA damage and carcinogenesis, retroviral
      oncogenes have not yet been shown to affect the DNA damage-signaling pathway. In
      this report, we show that Finkel-Biskis-Reilly mouse osteosarcoma virus (FBR) v
      fos, the retroviral homologue of the c-fos proto-oncogene, inhibits the cellular
      response to ionizing radiation. Cells that express FBR v-Fos show a decreased
      ability to repair DNA damage caused by ionizing radiation, and these cells show
      decreased survival in response to ionizing radiation. In addition, FBR v-Fos
      inhibits DNA-dependent protein kinase, a kinase specifically activated upon
      exposure to ionizing radiation. These effects were specific to ionizing
      radiation, as no effect of FBR v-Fos on the UV light signaling pathway was seen.
      Last, these effects were dependent on a lipid modification required for FBR v-Fos
      tumorigenesis, that of myristoylation of FBR v-Fos. A non-myristoylated mutant
      FBR v-Fos caused none of these effects. This study suggests that a retroviral
      oncogene can lead to an increased genomic instability, which can ultimately
      increase the carcinogenic potential of a cell.

PMID- 9162017
TI  - The prolactin receptor and severely truncated erythropoietin receptors support
      differentiation of erythroid progenitors.
AB  - Activation of the erythropoietin receptor is essential for the survival,
      proliferation, and differentiation of erythroid progenitors. To understand the
      role of erythropoietin receptor (EpoR) activation in erythroid differentiation,
      we infected primary erythroid progenitors with high-titer retrovirus encoding the
      non-hematopoietic prolactin receptor. The infected progenitors responded to
      prolactin in the absence of Epo by generating fully differentiated erythroid
      colonies. Therefore, differentiation of erythroid progenitors does not require an
      intracellular signal generated uniquely by the EpoR; the EpoR does not have an
      instructive role in erythroid differentiation. We also infected primary erythroid
      progenitors with retrovirus encoding chimeric receptors containing the
      extracellular domain of PrlR and the intracellular domain of either the wild-type
      or truncated EpoRs. A chimeric receptor containing only the membrane-proximal 136
      amino acids of the EpoR cytoplasmic domain efficiently supported prolactin
      dependent differentiation of erythroid progenitors. Substitution of the single
      cytoplasmic domain tyrosine in this receptor with phenylalanine (Y343F)
      eliminated its ability to support differentiation. The minimal EpoR cytoplasmic
      domain required for erythroid differentiation is therefore the same as that
      previously reported to be sufficient to support cell proliferation (D'Andrea, A.
      D., Yoshimura, A., Youssoufian, H., Zon, L. I., Koo, J. W., and Lodish, H. F.
      (1991) Mol. Cell. Biol. 11, 1980-1987; Miura, O., D'Andrea, A. D., Kabat, D., and
      Ihle, J. N. (1991) Mol. Cell. Biol. 11, 4895-4902; He, T.-C., Jiang, N., Zhuang,
      H., Quelle, D. E., and Wojchowski, D. M. (1994) J. Biol. Chem. 269, 18291-18294).

PMID- 9162018
TI  - Epidermal growth factor induces ubiquitination of Eps15.
AB  - Epidermal growth factor (EGF) receptor pathway substrate clone 15 (Eps15) has
      been described as a 142-kDa EGF receptor substrate. It has been shown to bind to
      the EGF receptor, adaptor protein-2, and clathrin and is present at clathrin
      coated pits and vesicles. Upon stimulation of cells with EGF or transforming
      growth factor alpha, Eps15 becomes rapidly and transiently phosphorylated on
      tyrosine residues. This phosphorylation coincides with an increase of 8 kDa in
      molecular mass. Here we show that this increase in molecular mass is not due to
      tyrosine phosphorylation. Instead, we found both by Western blotting and protein
      sequencing that this EGF-induced increase in molecular mass is the result of
      monoubiquitination. Eps15 ubiquitination but not tyrosine phosphorylation was
      inhibited under conditions that blocked EGF-induced internalization of the EGF
      receptor. Our results establish ubiquitination as a second form of EGF-stimulated
      covalent modification of Eps15.

PMID- 9162019
TI  - Involvement of proteasomes in regulating Jak-STAT pathways upon interleukin-2
      stimulation.
AB  - Interleukin-2 (IL-2) activates the receptor-associated Janus family tyrosine
      kinases, Jak1 and Jak3, which in turn phosphorylate and activate specific STAT
      proteins (signal transducers and activators of transcription), such as STAT5.
      Activation of Jak and STAT proteins by IL-2 is transient and the mechanism for
      the subsequent down-regulation of their activity is largely unknown. We report
      here that IL-2-induced DNA-binding activity and tyrosine phosphorylation of STAT5
      are stabilized by a proteasome inhibitor MG132; however, no detectable
      ubiquitination of the STAT proteins is observed. This sustained STAT5 activation
      can be blocked by protein kinase inhibitors, which is consistent with the ability
      of the proteasome inhibitor to stabilize IL-2-induced tyrosine phosphorylation of
      Jak1 and Jak3. These results suggest that proteasome-mediated protein degradation
      modulates protein-tyrosine phosphatase activity that negatively regulates the Jak
      STAT signaling pathways.

PMID- 9162020
TI  - Inactivation of a voltage-dependent K+ channel by beta subunit. Modulation by a
      phosphorylation-dependent interaction between the distal C terminus of alpha
      subunit and cytoskeleton.
AB  - Kv1.1/Kvbeta1.1 (alphabeta) K+ channel expressed in Xenopus oocytes was shown to
      have a fast inactivating current component. The fraction of this component
      (extent of inactivation) is increased by microfilament disruption induced by
      cytochalasins or by phosphorylation of the alpha subunit at Ser-446, which
      impairs the interaction of the channel with microfilaments. The relevant sites of
      interaction on the channel molecules have not been identified. Using a
      phosphorylation-deficient mutant of alpha, S446A, to ensure maximal basal
      interaction of the channel with the cytoskeleton, we show that one relevant site
      is the end of the C terminus of alpha. Truncation of the last six amino acids
      resulted in alphabeta channels with an extent of inactivation up to 2.5-fold
      larger and its further enhancement by cytochalasins being reduced 2-fold. The
      wild-type channels exhibited strong inactivation, which could not be markedly
      increased either by cytochalasins or by the C-terminal mutations, indicating that
      the interaction of the wild-type channels with microfilaments was minimal to
      begin with, presumably because of extensive basal phosphorylation. Since the C
      terminal end of Kv1.1 was shown to participate in channel clustering via an
      interaction with members of the PSD-95 family of proteins, we propose that a
      similar interaction with an endogenous protein takes place, contributing to
      channel connection to the oocyte cytoskeleton. This is the first report to assign
      a modulatory role to such an interaction: together with the state of
      phosphorylation of the channel, it regulates the extent of inactivation conferred
      by the beta subunit.

PMID- 9162021
TI  - The hemochromatosis founder mutation in HLA-H disrupts beta2-microglobulin
      interaction and cell surface expression.
AB  - We recently reported the positional cloning of a candidate gene for hereditary
      hemochromatosis (HH), called HLA-H, which is a novel member of the major
      histocompatibility complex class I family. A mutation in this gene, cysteine 282 
      -> tyrosine (C282Y), was found to be present in 83% of HH patient DNAs, while a
      second variant, histidine 63 --> aspartate (H63D), was enriched in patients
      heterozygous for C282Y. The functional relevance of either mutation has not been
      described. Co-immunoprecipitation studies of cell lysates from human embryonic
      kidney cells transfected with wild-type or mutant HLA-H cDNA demonstrate that
      wild-type HLA-H binds beta2-microglobulin and that the C282Y mutation, but not
      the H63D mutation, completely abrogates this interaction. Immunofluorescence
      labeling and subcellular fractionations demonstrate that while the wild-type and
      H63D HLA-H proteins are expressed on the cell surface, the C282Y mutant protein
      is localized exclusively intracellularly. This report describes the first
      functional significance of the C282Y mutation by suggesting that an abnormality
      in protein trafficking and/or cell-surface expression of HLA-H leads to HH
      disease.

PMID- 9162022
TI  - Herpesvirus entry mediator, a member of the tumor necrosis factor receptor (TNFR)
      family, interacts with members of the TNFR-associated factor family and activates
      the transcription factors NF-kappaB and AP-1.
AB  - The mammalian tumor necrosis factor receptor (TNFR) family consists of 10 cell
      surface proteins that regulate development and homeostasis of the immune system.
      Based on an expressed sequence tag, we have cloned a cDNA encoding a novel member
      of the human TNFR family. A closely related protein, designated HVEM (for
      herpesvirus entry mediator), was identified independently by another group as a
      mediator of herpesvirus entry into mammalian cells (Montgomery, R., Warner, M.,
      Lum, B., and Spear, P. (1996) Cell 87, 427-436). HVEM differed from our clone by
      two amino acid residues, suggesting that the two proteins represent polymorphism
      of a single HVEM gene. We detected HVEM mRNA expression in several human fetal
      and adult tissues, although the predominant sites of expression were lymphocyte
      rich tissues such as adult spleen and peripheral blood leukocytes. The
      cytoplasmic region of HVEM bound to several members of the TNFR-associated factor
      (TRAF) family, namely TRAF1, TRAF2, TRAF3, and TRAF5, but not to TRAF6. Transient
      transfection of HVEM into human 293 cells caused marked activation of nuclear
      factor-kappaB (NF-kappaB), a transcriptional regulator of multiple
      immunomodulatory and inflammatory genes. HVEM transfection induced also marked
      activation of Jun N-terminal kinase, and of the Jun-containing transcription
      factor AP-1, a regulator of cellular stress-response genes. These results suggest
      that HVEM is linked via TRAFs to signal transduction pathways that activate the
      immune response.

PMID- 9162023
TI  - A key amino acid responsible for substrate selectivity of monoamine oxidase A and
      B.
AB  - Monoamine oxidase (MAO) oxidizes biologically important amines including
      neurotransmitters and plays a central role in the regulation of intracellular
      level of these amines. Two distinct forms of MAO (MAO A and MAO B) were defined
      based on differences in substrate and inhibitor specificities. We earlier
      reported that the region between about residues 120 and 220 of rat MAO is
      responsible for determination of the substrate selectivity of MAO A and B
      (Tsugeno, Y. Hirashiki, I., Ogata, F., and Ito, A. (1995) J. Biochem. (Tokyo)
      118, 974-980). To determine the essential amino acids in this region that
      participate in substrate recognition, a series of mutant enzymes in which amino
      acid residues that are conserved among various species but are different between
      the two forms of the enzyme were replaced with the corresponding amino acids of
      the counterpart and were engineered from the cDNAs of rat liver MAO A and B, and
      affinities for several substrates were examined. A single mutation in which Phe
      208 in MAO A was substituted by the corresponding residue of Ile in MAO B was
      sufficient to convert the A-type substrate selectivity, and the reverse was
      exactly the case. Phe at this position was replaceable with Tyr for the A-type
      specificity and Ile was replaceable with Val and Ala for the B-type. Thus,
      aromatic and aliphatic residues seem to contribute to render substrate
      selectivity of MAO A and MAO B, respectively.

PMID- 9162024
TI  - Cystic fibrosis transmembrane conductance regulator inverts protein kinase A
      mediated regulation of epithelial sodium channel single channel kinetics.
AB  - Abnormal regulation of ion channels by members of the ABC transport protein
      superfamily has been implicated in hyperinsulinemic hypoglycemia and in excessive
      Na+ absorption by airway epithelia in cystic fibrosis (CF). How ABC proteins
      regulate ion conductances is unknown, but must generally involve either the
      number or activity of specific ion channels. Here we report that the cystic
      fibrosis transmembrane conductance regulator (CFTR), which is defective in CF,
      reverses the regulation of the activity of single epithelial sodium channels
      (ENaC) by cAMP. ENaC expressed alone in fibroblasts responded to activation of
      cAMP-dependent protein kinase with increased open probability (Po) and mean open
      time, whereas ENaC co-expressed with CFTR exhibited decreased Po and mean open
      time under conditions optimal for PKA-mediated protein phosphorylation. Thus,
      CFTR regulates ENaC at the level of single channel gating, by switching the
      response of single channel Po to cAMP from an increase to a decrease.

PMID- 9162026
TI  - Critical role of human bisphosphoglycerate mutase Cys22 in the phosphatase
      activator-binding site.
AB  - The enzymatic activities catalyzed by bisphosphoglycerate mutase (BPGM, EC
      5.4.2.4) have been shown to occur at a unique active site, with distinct binding
      sites for diphosphoglycerates and monophosphoglycerates. The physiological
      phosphatase activator (2-phosphoglycolate) binds to BPGM at an undetermined site.
      BPGM variants were constructed by site-directed mutagenesis of three amino acid
      residues in the active site to identify residues specifically involved in the
      binding of the monophosphoglycerates and 2-phosphoglycolate. Substitution of
      Cys22 by functionally conservative residues, Thr or Ser, caused a great decrease
      in 2-phosphoglycolate-stimulated phosphatase activity and in the Ka value of the
      activator, whereas it caused no change in other catalytic activities or in the Km
      values of 2,3-diphosphoglycerate (2,3-DPG) and glycerate 3-phosphate (3-PG, EC
      1.1.1.12), indicating that Cys22 is specifically involved either directly or
      indirectly in 2-phosphoglycolate binding. Kinetic experiments showed that the Ka
      of the cofactor and the Km of 3-PG were affected by the substitution of Ser23
      indicating that this residue is necessary for the fixation of both 3-PG and 2
      phosphoglycolate. The R89K variant has previously been shown to have a modified
      Km value for monophosphoglycerates, however, its affinity for 2-phosphoglycolate
      is unaltered, suggesting that Arg89 is specifically involved in
      monophosphoglycerates binding. CD spectroscopic studies of substrates and
      cofactor binding showed that 2,3-DPG induced structural modifications of normal
      and mutated enzymes which could be due to protein phosphorylation. Addition of 2
      phosphoglycolate to phosphorylated proteins with normal affinity for the cofactor
      produced spectra with the same characteristics as unphosphorylated species. In
      summary, monophosphoglycerates and 2-phosphoglycolate have partially distinct
      binding sites in human BPGM. The specific implication of the Cys22 residue in 2
      phosphoglycolate binding is of great significance in the design of analogs of
      therapeutic benefit.

PMID- 9162025
TI  - The Jun kinase/stress-activated protein kinase pathway functions to regulate DNA
      repair and inhibition of the pathway sensitizes tumor cells to cisplatin.
AB  - We have studied the role of Jun/stress-activated protein kinase (JNK/SAPK)
      pathway in DNA repair and cisplatin resistance in T98G glioblastoma cells.
      JUN/SAPK is activated by DNA damage and phosphorylates serines 63 and 73 in the N
      terminal domain of c-Jun, which is known to increase its transactivation
      properties. We show that treatment of T98G glioblastoma cells with cisplatin but
      not the transplatin isomer activates JNK/SAPK about 10-fold. T98G cells, which
      are highly resistent to cisplatin (IC50 = 140 +/- 13 microM), modified to express
      a nonphosphorylatable dominant negative c-Jun (termed dnJun) exhibit decreased
      viability following treatment with cisplatin, but not transplatin, in proportion
      (rPearson = 0.98) to the level of dnJun expressed leading to a 7-fold decreased
      IC50. Similar effects are observed in U87 cells, PC-3 cells, and MCF-7 cells, as
      well as in T98G cells modified to express TAM-67, a known inhibitor of c-Jun
      function. In contrast, no sensitization effect was observed in cells modified to
      express wild-type c-Jun. Furthermore, through quantitative polymerase chain
      reaction-stop assays, we show that dnJun expressing cells were inhibited in
      repair of cisplatin adducts (p = 0.55), whereas repair is readily detectable (p =
      0.003) in parental cells. These observations indicate that the JNK/SAPK pathway
      is activated by cisplatin-induced DNA damage and that this response is required
      for DNA repair and viability following cisplatin treatment. Regulation of DNA
      repair following genotoxic stress may be a normal physiological role of the
      JNK/SAPK pathway.

PMID- 9162027
TI  - The active state of the thin filament is destabilized by an internal deletion in
      tropomyosin.
AB  - The function of three of tropomyosin's sequential quasiequivalent regions was
      studied by deletion from skeletal muscle alpha-tropomyosin of internal residues
      49-167. This deletion mutant tropomyosin spans four instead of the normal seven
      actins, and most of the tropomyosin region believed to interact with troponin is
      retained and uninterrupted in the mutant. The mutant tropomyosin was compared
      with a full-length control molecule that was modified to functionally resemble
      muscle tropomyosin (Monteiro, P. B., Lataro, R. C., Ferro, J. A., and Reinach, F.
      C. (1994) J. Biol. Chem. 269, 10461-10466). The tropomyosin deletion suppressed
      the actin-myosin subfragment 1 MgATPase rate and the in vitro sliding of thin
      filaments over a heavy meromyosin-coated surface. This inhibition was not
      reversed by troponin plus Ca2+. Comparable tropomyosin affinities for actin,
      regardless of the deletion, suggest that the deleted region has little
      interaction with actin in the absence of other proteins. Similarly, the deletion
      did not weaken binding of the troponin-tropomyosin complex to actin. Furthermore,
      Ca2+ had a 2-fold effect on troponin-tropomyosin's affinity for actin, regardless
      of the deletion. Notably, the deletion greatly weakened tropomyosin binding to
      myosin subfragment 1-decorated actin, with the full-length tropomyosin having a
      100-fold greater affinity. The inhibitory properties resulting from the deletion
      are attributed to defective stabilization of the myosin-induced active state of
      the thin filament.

PMID- 9162028
TI  - The MEKK-JNK pathway is stimulated by alpha1-adrenergic receptor and ras
      activation and is associated with in vitro and in vivo cardiac hypertrophy.
AB  - In neonatal rat ventricular myocytes, stimulation of the alpha1-adrenergic
      receptor (alpha1-AdrR) activates a program of genetic and morphological changes
      characterized by transcriptional activation of the atrial natriuretic factor
      (ANF) gene and enlargement (hypertrophy) of the cells. The low molecular weight
      GTPase Ras has been established as an important regulator of hypertrophy both in
      vitro and in vivo. Ras activates a kinase cascade involving Raf, the mitogen
      activated protein kinase kinase (MEK), and the extracellular signal-regulated
      protein kinase (ERK). However, the extent of involvement of this pathway in
      regulating hypertrophic responses is controversial. We demonstrate here that both
      alpha1-AdrR stimulation and Ras can also activate the c-Jun NH2-terminal kinase
      (JNK) in cardiomyocytes. The alpha1-AdrR effect on JNK occurs through a pathway
      requiring Ras and MEK kinase (MEKK). A constitutively activated mutant of MEKK
      that preferentially activates JNK, stimulates ANF reporter gene expression, while
      a dominant negative MEKK mutant inhibits ANF expression induced by PE.
      Furthermore, JNK activity is increased in the ventricles of mice overexpressing
      oncogenic Ras, whereas ERK activity is not. These results suggest that the alpha1
      AdrR mediates ANF gene expression through a Ras-MEKK-JNK pathway and that
      activation of this pathway is associated with in vitro and in vivo hypertrophy.

PMID- 9162029
TI  - Evolution of a fetal expression pattern via cis changes near the gamma globin
      gene.
AB  - One basis for the evolution of organisms is the acquisition of new temporal and
      spatial domains of gene expression. Such novel expression domains could be
      generated either by cis sequence changes that alter the complement of trans
      acting regulators binding to control elements or by changes in the expression
      patterns of one or more of the regulatory (trans) factors themselves. The gamma
      globin gene is a prime example of a gene that has undergone a distinct change in
      temporal expression at a defined time in evolution. Approximately 35-55 million
      years ago, the previously embryonic gamma gene acquired a fetal expression
      pattern. This change occurred in a simian primate ancestor after the separation
      of simian and prosimian primates but before the further separation of the major
      simian lineages; thus, the (prosimian) galago gamma gene retains the ancestral
      embryonic expression pattern, whereas the (simian) human gamma gene is fetal.
      This analysis of galago and human gamma genes in transgenic mice demonstrates
      that cis changes in sequences within a 4.0-kilobase region surrounding the gamma
      gene were responsible for the evolution of a novel fetal expression pattern in
      the gamma globin genes of simian primates.

PMID- 9162030
TI  - Characterization of protein-tyrosine phosphatases that dephosphorylate the high
      affinity IgE receptor.
AB  - An early event that follows aggregation of the high affinity receptor for IgE
      (FcepsilonRI) is the phosphorylation of protein tyrosines, especially those on
      the beta- and gamma-subunits of the receptor. Disaggregation of the receptors
      leads to their rapid dephosphorylation, but even stably aggregated receptors
      undergo continual rounds of phosphorylation and dephosphorylation. We developed
      assays to study dephosphorylation of the receptors and other cellular proteins.
      Whole cell extracts dephosphorylated both subunits of the receptors rapidly and
      were as active against aggregated as against disaggregated FcepsilonRI. Upon
      disaggregation, the in vivo dephosphorylation of the FcepsilonRI and several
      other proteins followed first-order kinetics with closely similar rate constants
      despite substantial differences in the extent of phosphorylation. These results
      suggest that the level of phosphorylation of FcepsilonRI is largely controlled by
      the aggregation-induced action of kinase(s) and not from changes in
      susceptibility to or activity of the phosphatases. Much of the total phosphatase
      is lost when the cells are permeabilized, but the rate of dephosphorylation of
      disaggregated FcepsilonRI was comparable in intact and permeabilized cells. Thus,
      much of the activity utilized by the cell to dephosphorylate the FcepsilonRI is
      likely to be associated with the plasma membrane.

PMID- 9162031
TI  - Arginine 200 of heparin cofactor II promotes intramolecular interactions of the
      acidic domain. Implication for thrombin inhibition.
AB  - Heparin cofactor II (HCII) is presumed to be a physiological inhibitor of the
      serine proteinase thrombin. The reaction between HCII and thrombin is quite
      unique, because it involves an unusual HCII-reactive site loop sequence of Leu444
      Ser445, requires the presence of glycosaminoglycans for optimal activity and
      involves a protein-protein interaction besides the reactive site loop-active site
      interaction characteristic of serine proteinase inhibitor-serine proteinase
      pairs. Two mutations at a unique HCII residue, Arg200 --> Ala or Glu, were
      generated by site-directed mutagenesis. The mutations did not alter either HCII
      binding to heparin-Sepharose or HCII inhibition of thrombin in the presence of
      heparin or dermatan sulfate, suggesting that Arg200 is not part of the
      glycosaminoglycan binding site of HCII. In the absence of glycosaminoglycan,
      there was a significant increase in alpha-thrombin inhibition by the Arg200
      mutants as compared with wild type recombinant HCII (wt-rHCII), whereas
      inhibition rates with chymotrypsin were identical. Inhibition of gammaT-thrombin,
      which lacks anion-binding exosite 1 ((ABE-1), the region of alpha-thrombin that
      interacts with the acidic domain of HCII), was significantly reduced compared
      with alpha-thrombin, but the reduction was more dramatic for the Arg200-rHCII
      mutants. Hirugen, which binds to ABE-1 of alpha-thrombin, also diminished
      inhibition of alpha-thrombin by the Arg200-rHCII mutants to nearly wt-rHCII
      levels. Both Arg200-rHCII mutants had significantly increased ka values as
      compared with wt-rHCII, whereas the kd rates were unchanged. Collectively, these
      results suggest that the improved inhibitory activity of the Arg200-rHCII mutants
      is mediated by enhanced interactions between the acidic domain and ABE-1,
      resulting in an increased HCII-thrombin association rate.

PMID- 9162032
TI  - How GroES regulates binding of nonnative protein to GroEL.
AB  - At present, it is still enigmatic how the reaction cycle by which the Escherichia
      coli GroE chaperones mediate protein folding in the cell is coordinated with
      respect to the sequential order of binding and release of GroES, nucleotide, and
      nonnative protein. It is generally assumed that the asymmetric GroEL.GroES
      complex is the acceptor state for substrate protein. Nevertheless, this species
      is poorly understood in its binding characteristics for nucleotide and nonnative
      protein. We show here that this species has a high affinity binding site for
      nonnative protein. In addition to this, binding of nucleotide to one GroEL ring
      is strongly favored by GroES binding to the other ring. However, the slow rate of
      release of substrate protein from the unproductive trans-position kinetically
      favors the binding of a second GroES, thereby forming a symmetric
      GroEL14.(GroES7)2 complex and simultaneously ensuring that substrate protein is
      sequestered in a position underneath GroES. Our results demonstrate that the
      intrinsic binding characteristics of the trans-bullet complex determine the
      sequence of events during the reaction cycle.

PMID- 9162033
TI  - Androgen and glucocorticoid receptor heterodimer formation. A possible mechanism
      for mutual inhibition of transcriptional activity.
AB  - The androgen and glucocorticoid hormones elicit divergent and often opposing
      effects in cells, tissues, and animals. A wide range of physiological and
      molecular biological evidence suggests that the receptors that mediate these
      effects, the androgen and glucocorticoid receptors (AR and GR, respectively),
      influence each other's transcriptional activity. We now show that coexpressed AR
      and GR indeed do interact at the transcriptional level and that this interaction
      is correlated with their ability to form heterodimers at a common DNA site, in
      vitro and in vivo. Furthermore, mutants that cannot heterodimerize do not inhibit
      each other's activity. These observations provide the first evidence that the
      opposing physiological effects of the androgen and glucocorticoid hormones are
      due to the direct physical interaction between their receptors at the
      transcriptional level.

PMID- 9162034
TI  - Direct demonstration of geranylgeranylation and farnesylation of Ki-Ras in vivo.
AB  - It has recently been reported that Ki-Ras protein can be modified in vitro by
      farnesylation or geranylgeranylation. However, a previous analysis of Ki-Ras
      prenylation in vivo found only farnesylated Ki-Ras. In this report it is shown
      that under normal conditions, Ki-Ras is farnesylated in vivo and when cells are
      treated with the farnesyl transferase inhibitors B956 or B957, farnesylation is
      inhibited and Ki-Ras becomes geranylgeranylated in a dose dependent manner. These
      results have strong implications in the design of anticancer drugs based on
      inhibition of prenylation.

PMID- 9162035
TI  - Prolactin stimulates serine/tyrosine phosphorylation and formation of
      heterocomplexes of multiple Stat5 isoforms in Nb2 lymphocytes.
AB  - Transcription factors of the Stat gene family are selectively activated by many
      hormones and cytokines. Stat5 originally was cloned as a prolactin-stimulated DNA
      binding protein, but is also activated by non-lactogenic cytokines in many cell
      types. The recent identification of two distinct Stat5 genes, which encode a 94
      kDa Stat5a and a 92-kDa Stat5b as well as several lower molecular weight
      isoforms, suggests additional complexity and combinatorial possibilities for
      transcriptional regulation. We now report a biochemical analysis of prolactin
      activation of Stat proteins in Nb2 lymphocytes, which was associated with: 1)
      rapid tyrosine phosphorylation of Stat5a, Stat5b, a COOH-terminally truncated 80
      kDa Stat5 form, Stat1alpha, and Stat3; 2) rapid and selective formation of
      Stat5a/b heterodimers, without involvement of Stat1alpha or Stat3; 3) marked
      serine, but not threonine phosphorylation of Stat5a and Stat5b; and 4) the
      appearance of two qualitatively distinct Stat5 protein complexes, which
      discriminated between oligonucleotides corresponding to the prolactin response
      elements of the beta-casein and interferon regulatory factor-1 gene promoters.
      Collectively, our analyses showed that Stat5a and Stat5b respond similarly to
      prolactin receptor activation, but also suggested that the two genes have evolved
      unique properties that may contribute to the specificity of receptors that
      utilize Stat5 signaling proteins.

PMID- 9162036
TI  - Serine 331 and tyrosine 333 are both involved in the interaction between the
      cytosolic domain of TGN38 and the mu2 subunit of the AP2 clathrin adaptor
      complex.
AB  - TGN38 is a type I integral membrane protein that cycles between the trans-Golgi
      network and the plasma membrane. Internalization at the cell surface and
      targeting back to the trans-Golgi network is dependent on a hexapeptide motif,
      SDYQRL, in the cytosolic tail of the protein. It was recently demonstrated that
      this motif specifically interacts with the mu2 subunit of the AP2 adaptor
      complex. We have studied the interaction between the entire cytosolic domain of
      TGN38 and mu2 using the yeast two hybrid system, in vitro binding of recombinant
      fusion proteins and IAsys optical biosensor technology. A specific interaction
      has been demonstrated in each of the systems we have employed. We have shown an
      absolute requirement for Tyr-333 of TGN38 in binding to mu2. In addition we found
      that mutation of Ser-331 to alanine reduces the affinity of the interaction. By
      measuring tryptophan fluorescence at equilibrium, we have also determined the
      dissociation constant for the interaction between the entire cytosolic tail of
      TGN38 and mu2 as 58 nM. In contrast to previously published work, our data
      suggest that not only Tyr-333 but also its context is important in determining
      the specificity of binding of TGN38 to mu2.

PMID- 9162037
TI  - Regulation of the ERBB-2 promoter by RBPJkappa and NOTCH.
AB  - Within the human ERBB-2 gene promoter, a 100-base pair region 5' to the TATA box
      enhances basal transcription 200-fold. Two palindromes present within this 100
      base pair region are important for transcription. The palindrome binding protein
      was purified to homogeneity and found to be identical to RBPJkappa, the mammalian
      homolog of Drosophila Suppressor of Hairless (Su(H)). Recombinant RBPJkappa bound
      the ERBB-2 promoter with affinity comparable with that seen with well
      characterized RBPJkappa binding sites. RBPJkappa activated an ERBB-2 palindrome
      containing promoter in 293 cells. Because in Drosophila Su(H) acts downstream of
      NOTCH and because NOTCH.Su(H)/RBPJkappa stimulates transcription from target
      promoters, NOTCH-IC, a constitutively active form of NOTCH, was tested for
      effects on the ERBB-2 palindrome. NOTCH-IC further increased RBPJkappa-mediated
      transcription on wild type but not mutant ERBB-2 palindrome. Thus, RBPJkappa can
      activate ERBB-2 transcription and serve as an anchor to mediate NOTCH function on
      the ERBB-2 gene.

PMID- 9162038
TI  - 1alpha,25-dihydroxyvitamin D3-24-hydroxylase (CYP24) hydroxylates the carbon at
      the end of the side chain (C-26) of the C-24-fluorinated analog of 1alpha,25
      dihydroxyvitamin D3.
AB  - The sequential oxidation and cleavage of the side chain of 1alpha, 25
      dihydroxyvitamin D3 (1alpha,25(OH)2D3) initiated by the hydroxylation at C-24 is
      considered to be the major pathway of this hormone in the target cell metabolism.
      In this study, we examined renal metabolism of a synthetic analog of
      1alpha,25(OH)2D3, 24, 24-difluoro-1alpha,25-dihydroxyvitamin D3 (F2
      1alpha,25(OH)2D3), C-24 of which was designed to resist metabolic hydroxylation.
      When kidney homogenates prepared from 1alpha,25(OH)2D3-supplemented rats were
      incubated with F2-1alpha,25(OH)2D3, it was mainly converted to a more polar
      metabolite. We isolated and unequivocally identified the metabolite as 24,24
      difluoro-1alpha,25,26-trihydroxyvitamin D3 (F2-1alpha,25,26(OH)3D3) by
      ultraviolet absorption spectrometry, frit-fast atom bombardment liquid
      chromatography/mass spectroscopy analysis, and direct comparison with chemically
      synthesized F2-1alpha,25,26(OH)3D3. Metabolism of F2-1alpha,25(OH)2D3 into F2
      1alpha,25,26(OH)3D3 by kidney homogenates was induced by the prior administration
      of 1alpha,25(OH)2D3 into rats. The C-24 oxidation of 1alpha,25(OH)2D3 in renal
      homogenates was inhibited by F2-1alpha,25(OH)2D3 in a concentration-dependent
      manner. Moreover, F2-1alpha,25,26(OH)3D3 was formed in ROS17/2.8 cells
      transfected with a plasmid expressing 1alpha,25(OH)2D3-24-hydroxylase (CYP24) but
      not in the cells transfected with that expressing vitamin D3-25-hydroxylase
      (CYP27) or containing inverted CYP27 cDNA. These results show that CYP24
      catalyzes not only hydroxylation at C-24 and C-23 of 1alpha,25(OH)2D3 but also at
      C-26 of F2-1alpha,25(OH)2D3, indicating that this enzyme has a broader substrate
      specificity of the hydroxylation sites than previously considered.

PMID- 9162039
TI  - Post-translational modifications in cartilage oligomeric matrix protein.
      Characterization of the N-linked oligosaccharides by matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry.
AB  - Analysis of the carboxymethylated subunit of human cartilage oligomeric matrix
      protein (COMP) by matrix-assisted laser desorption time-of-flight mass
      spectrometry indicated a protonated molecular mass of 86949 +/- 149 Da, compared
      with 83547.0 Da calculated from the sequence. Treatment with N-glycanase caused a
      reduction in mass of 3571 +/- 219 Da, but there was no loss of mass after
      treatment with O-glycanase or neuraminidase. Peptides containing two putative
      sites of N-glycosylation were purified and characterized. Analysis of the masses
      of these after N-glycanase treatment indicated that one was substituted at Asn
      101 with an oligosaccharide of mass 1847. 2 +/- 6.6 Da, and the other was
      unsubstituted at Asn-124. The remaining site of attachment, at Asn-721, was,
      therefore, also substituted with an oligosaccharide of mass 1724 +/- 226 Da.
      Analysis of the total monosaccharide content by chemical methods indicated that
      there were no additional oligosaccharide substituents. The MALDI-TOF mass spectra
      of COMP from bovine fetal and adult cartilage were compared, indicating a more
      heterogeneous pattern of substitution at Asn-101 in the fetal form. Since COMP is
      distributed throughout the pericellular and territorial environments in
      developing cartilage but occupies the interterritorial zone in mature cartilage,
      these changes in glycosylation may allow for different intermolecular
      interactions.

PMID- 9162040
TI  - Reading-frame restoration by transcriptional slippage at long stretches of
      adenine residues in mammalian cells.
AB  - We previously characterized a mutant apoB allele (the apoB86 allele) that
      produces both a truncated apoB (apoB86) and a full-length apoB100. The mutant
      allele contained a deletion of a single cytosine in exon 26, creating a stretch
      of eight consecutive adenines in the -1 reading frame. The altered reading-frame
      allele was restored, with approximately 10% efficiency, by the transcriptional
      insertion of an extra adenine into the stretch of eight consecutive adenines,
      thereby accounting for the synthesis of the full-length apoB100. Here, we
      demonstrate that this reading-frame restoration does not occur when the long
      stretch of adenines is interrupted by a cytosine. To assess whether reading-frame
      restoration is unique to a single site in the apoB gene, the same mutation (eight
      consecutive adenines in the -1 reading frame) was inserted into another site
      within the apoB gene. Reading-frame restoration occurred at the second site and
      was abrogated when the stretch of adenines was interrupted by another base. Of
      note, a computerized analysis of human cDNA sequences revealed that long
      stretches of adenines in protein-coding sequences occur at a lower than predicted
      frequency, suggesting that evolution has selected against these sequences.

PMID- 9162041
TI  - Sequential interchange of four amino acids from blood group B to blood group A
      glycosyltransferase boosts catalytic activity and progressively modifies
      substrate recognition in human recombinant enzymes.
AB  - The human blood group A and B glycosyltransferase enzymes are highly homologous
      and the alteration of four critical amino acid residues (Arg-176 --> Gly, Gly-235
      --> Ser, Leu-266 --> Met, and Gly-268 --> Ala) is sufficient to change the enzyme
      specificity from a blood group A to a blood group B glycosyltransferase. To carry
      out a systematic study, a synthetic gene strategy was employed to obtain their
      genes and to allow facile mutagenesis. Soluble forms of a recombinant
      glycosyltransferase A and a set of hybrid glycosyltransferase A and B mutants
      were expressed in Escherichia coli in high yields, which allowed them to be
      kinetically characterized extensively for the first time. A functional hybrid A/B
      mutant enzyme was able to catalyze both A and B reactions, with the kcat being 5
      fold higher for the A donor. Surprisingly, even a single amino acid replacement
      in glycosyltransferase A with the corresponding residue from glycosyltransferase
      B (Arg-176 --> Gly) produced enzymes with glycosyltransferase A activity only,
      but with very large (11-fold) increases in the kcat and increased specificity.
      The increases observed in kcat are among the largest obtained for a single amino
      acid change and are advantageous for the preparative scale synthesis of blood
      group antigens.

PMID- 9162042
TI  - Epidermal growth factor induces CD44 gene expression through a novel regulatory
      element in mouse fibroblasts.
AB  - Growth factors coordinately regulate a variety of genes associated with
      pathological states including tumor invasion and metastasis. Overexpressed
      epidermal growth factor receptor (EGFR) on tumor cell surfaces is associated with
      enhanced cell attachment and migration into extracellular matrices, which
      promotes tumor aggressiveness. We have demonstrated that epidermal growth factor
      (EGF) up-regulates the cell surface adhesion molecule CD44 at both the mRNA and
      protein levels on mouse fibroblasts expressing full-length wild-type EGFR (NR6
      WT) but not on EGFR-deficient cells (NR6-P). This increases cell attachment to
      hyaluronic acid. In this investigation, transcriptional regulation of CD44 by EGF
      was confirmed by defining an EGF-regulatory element. By employing human CD44 gene
      promoter-chloramphenicol acetyltransferase (CAT) constructs transfected into NR6
      WT cells, EGF inducibility was observed within a 120-base pair (bp) DNA fragment
      located 450 bp upstream of the RNA initiation site. Differential EGF inducibility
      was found among different cell lines chosen, indicating a 3.2- and 1.8-fold
      enhancement in DU145 cells carrying exogenous wild-type EGFR and in MCF-7 cells,
      respectively, while minimal EGF induction was found in cervical cancer HeLa
      cells. Utilizing gel shift assays, a time-dependent increase of DNA-protein
      complex formation was found upon EGF stimulation in NR6-WT cells but not in NR6-P
      cells. Based upon these observations, a novel 22-bp EGF regulatory element (ERE)
      (5'--604CCCTCTCTCCAGCTCCTCTCCC-583-3') was isolated from the CD44 gene promoter.
      This ERE conferred DNA-protein binding ability in vitro, as well as the full
      functional recovery of EGF inducibility of CAT activity when linked to a
      homologous CD44 promoter or a SV40 promoter driving a CAT reporter gene. A two
      base mutation of the ERE completely eliminated its binding activity as well as
      its EGF inducibility of CAT expression. Our studies indicate that EGF induces
      CD44 gene expression through an interaction between a specific ERE and putative
      novel transcriptional factor so as to regulate cell attachment to extracellular
      matrix.

PMID- 9162043
TI  - Xenopus heat shock factor 1 is a nuclear protein before heat stress.
AB  - Stress-induced expression of the heat shock (hs) genes in eukaryotes is mediated
      by a transcription factor known as heat shock factor 1 (HSF1). HSF1 is present in
      a latent, monomeric form in unstressed metazoan cells and upon exposure to heat
      or other forms of stress is converted to an "active" trimeric form, which binds
      the promoters of hs genes and induces their transcription. The conversion of HSF1
      to its active form is hypothesized to be a multistep process involving (i)
      oligomerization of HSF1, plus (ii) additional changes in its physical
      conformation, (iii) changes in its phosphorylation state, and for some species
      (iv) translocation from the cytoplasm to the nucleus. Oligomerization of HSF
      appears to be essential for high affinity DNA binding, but it remains unclear
      whether the other steps occur in all organisms or what their mechanistic roles
      are. In this study we have examined if heat-induced cytoplasmic-nuclear
      translocation of HSF1 occurs in Xenopus oocytes. We observed that germinal
      vesicles (nuclei) that were physically dissected from unshocked Xenopus laevis
      oocytes contain no HSF1 binding activity. Interestingly, in vitro heat shock
      treatments of isolated nuclei from unshocked oocytes activated HSF1 binding,
      indicating that HSF1 must have been present in the unshocked nuclei prior to
      isolation. Induction of HSF1 binding was not observed in enucleated oocytes.
      Western blot analysis using an affinity-purified polyclonal antibody made against
      X. laevis HSF1 showed that HSF1 is present in equal amounts in unshocked and
      shocked oocytes and isolated nuclei. HSF1 was not detected in enucleated oocytes.
      These results clearly demonstrate that HSF1 is a nuclear protein in oocytes prior
      to exposure to stress. In Xenopus oocytes, therefore, HSF1 translocation from the
      cytoplasm to the nucleus is not part of the multistep process of HSF1 activation.
      These results also imply that the signals and/or factors involved in HSF1
      activation must have their effect in the nuclear compartment.

PMID- 9162044
TI  - Two homologous phosphorylation domains differentially contribute to
      desensitization and internalization of the m2 muscarinic acetylcholine receptor.
AB  - Short term exposure of m2 muscarinic acetylcholine receptors (m2 mAChRs) to
      agonist causes a rapid phosphorylation of the activated receptors, followed by a
      profound loss in the ability of the m2 mAChR to activate its signaling pathways.
      We have used site-directed mutagenesis to identify two clusters of Ser/Thr
      residues in the third intracellular loop of the m2 mAChR that can serve as
      redundant targets for agonist-dependent phosphorylation. Mutation of both
      clusters of Ser/Thr residues to alanines abolished agonist-dependent
      phosphorylation, while wild-type levels of m2 mAChR phosphorylation were observed
      in mutant receptors with only one or the other cluster mutated. However, the
      functional effects of phosphorylation of these two "redundant" clusters were not
      equivalent. No receptor desensitization was observed in an m2 mAChR with residues
      Thr307-Ser311 mutated to alanine residues. In contrast, mutation of the other
      Ser/Thr cluster, residues Ser286-Ser290, to alanines produced a receptor that
      continued to desensitize. Internalization of the m2 mAChR was promoted by
      phosphorylation of either cluster, suggesting that distinct mechanisms with
      unique structural requirements act downstream of m2 mAChR phosphorylation to
      mediate receptor desensitization and receptor internalization.

PMID- 9162045
TI  - Retinyl ester hydrolysis and retinol efflux from BFC-1beta adipocytes.
AB  - Adipose tissue is an important storage depot for retinol, but there are no data
      regarding retinol mobilization from adipose stores. To address this, dibutyryl
      cAMP was provided to murine BFC-1beta adipocytes and its effects on retinol
      efflux assessed. High performance liquid chromatography analysis of retinol and
      retinyl esters in adipocytes and media indicated that cAMP stimulated, in a time-
      and dose-dependent manner, retinol accumulation in the culture media and
      decreased cellular retinyl ester concentrations. Study of adipocyte retinol
      binding protein synthesis and secretion indicated that cAMP-stimulated retinol
      efflux into the media did not result from increased retinol-retinol-binding
      protein secretion but was dependent on the presence of fetal bovine serum in the
      culture media. Since our data suggested that retinyl esters can be hydrolyzed by
      a cAMP-dependent enzyme like hormone-sensitive lipase (HSL), in separate studies,
      we purified a HSL-containing fraction from BFC-1beta adipocytes and demonstrated
      that it catalyzed retinyl palmitate hydrolysis. Homogenates of Chinese hamster
      ovary cells overexpressing HSL catalyzed retinyl palmitate hydrolysis in a time-,
      protein-, and substrate-dependent manner, with an apparent Km for retinyl
      palmitate of 161 microM, whereas homogenates from control Chinese hamster ovary
      cells did not.

PMID- 9162046
TI  - Cloning and sequencing of two enterococcal glpK genes and regulation of the
      encoded glycerol kinases by phosphoenolpyruvate-dependent, phosphotransferase
      system-catalyzed phosphorylation of a single histidyl residue.
AB  - The glpK genes of Enterococcus casseliflavus and Enterococcus faecalis, encoding
      glycerol kinase, the key enzyme of glycerol uptake and metabolism in bacteria,
      have been cloned and sequenced. The translated amino acid sequences exhibit
      strong homology to the amino acid sequences of other bacterial glycerol kinases.
      After expression of the enterococcal glpK genes in Escherichia coli, both
      glycerol kinases were purified and were found to be phosphorylated by enzyme I
      and the histidine-containing protein of the phosphoenolpyruvate:glycose
      phosphotransferase system. Phosphoenolpyruvate-dependent phosphorylation caused a
      9-fold increase in enzyme activity. The site of phosphorylation in glycerol
      kinase of E. casseliflavus was determined as His-232. Site-specific mutagenesis
      was used to replace His-232 in glycerol kinase of E. casseliflavus with an
      alanyl, glutamate, or arginyl residue. The mutant proteins could no longer be
      phosphorylated confirming that His-232 of E. casseliflavus glycerol kinase
      represents the site of phosphorylation. The His232 --> Arg glycerol kinase
      exhibited an about 3-fold elevated activity compared with wild-type glycerol
      kinase. Fructose 1,6-bisphosphate was found to inhibit E. casseliflavus glycerol
      kinase activity. However, neither EIIAGlc from E. coli nor the EIIAGlc domain of
      Bacillus subtilis had an inhibitory effect on glycerol kinase of E.
      casseliflavus.

PMID- 9162047
TI  - The paired-domain regulates DNA binding by the homeodomain within the intact Pax
      3 protein.
AB  - Pax-3 contains two structurally independent DNA-binding domains, a paired-domain
      and a homeodomain. Their functional interdependence has been suggested by the
      analysis of the Sp-delayed (Spd) mouse mutant, in which a glycine to arginine
      substitution at position 9 of the paired-domain abrogates DNA binding by both
      domains. This glycine is located in the beta-turn portion of a beta-hairpin
      motif, and the requirement for this structure was investigated by mutagenesis at
      this and neighboring positions. At position 9, only substitution with proline
      increased DNA binding by the paired-domain and homeodomain above the level
      observed with the Spd arginine mutation, suggesting that the beta-turn is
      necessary for the function of both DNA-binding domains. Alanine scanning
      mutagenesis also identified a number of flanking residues important for DNA
      binding by both domains, emphasizing the requirement of the beta-hairpin for the
      interaction of Pax-3 with DNA. Furthermore, we show that these mutations reduce
      binding by the homeodomain at the monomeric level and do not impair dimerization
      on a TAAT(N)2ATTA consensus motif. In contrast, the wild-type paired-domain was
      found to prevent dimerization on consensus motifs with 3-base pair spacing of the
      type TAAT(N)3ATTA. Importantly, both the deleterious effect of the Spd mutation
      on homeodomain DNA binding and the loss of dimerization on TAAT(N)3ATTA motifs
      can be transferred to a heterologous homeodomain from the human phox protein.
      Moreover, the presence of the paired-domain affects sequence discrimination
      within the 3-base pair spacer in this context. These analyses establish that the
      beta-hairpin motif is essential for paired-domain and homeodomain DNA binding,
      and suggest a novel mechanism by which the paired-domain can influence sequence
      specificity of the homeodomain within the Pax-3 polypeptide.

PMID- 9162048
TI  - Bcl-2 modulates telomerase activity.
AB  - Apoptosis is a physiological mechanism of cell death that plays an important role
      in the regulation of tissue homeostasis. The regulation of apoptosis is a complex
      process and involves a number of gene products including the survival factor Bcl
      2, which has been found to be frequently deregulated in human cancers. In
      addition to deregulation of apoptosis, the process of neoplasia is also believed
      to be driven by the activation of telomerase, a ribonucleoprotein complex that
      adds telomeric repeats (hexanucleotide 5'-TTAGGG-3') to the ends of replicating
      chromosomes. Activation of telomerase has been detected in a vast majority of
      human cancer cells. Although recent studies have demonstrated the wide occurrence
      of telomerase activation and Bcl-2 deregulation in human cancer cells, it remains
      unclear whether there is any linkage between the deregulation of Bcl-2 and
      telomerase activity in cancer cells. In the studies presented here, we report
      that the stable overexpression of Bcl-2 in human cancer cells with low Bcl-2
      expression was accompanied by increased levels of telomerase activity. In
      addition, using an IL-2-dependent cytotoxic T-cell line, CTLL-2, we demonstrated
      that IL-2 deprivation (8 h), which is known to down-regulate Bcl-2 expression,
      also resulted in concurrent inhibition of telomerase activity in the absence of
      any detectable apoptosis and accumulation of cells in the G0/G1 phase of the cell
      cycle. Re-exposure of IL-2-deprived CTLL-2 cells to the recombinant IL-2 led to
      the up-regulation of both Bcl-2 expression and telomerase activity. Taken
      together, these findings establish a close linkage between the modulation of
      telomerase activity by survival factor Bcl-2, and provide a model to study
      regulation of telomerase activity by an anti-apoptotic pathway that is widely
      deregulated in cancer cells.

PMID- 9162049
TI  - Interleukin-1beta secreted from monocytic cells induces the expression of
      matrilysin in the prostatic cell line LNCaP.
AB  - Matrilysin is a matrix metalloprotease that is overexpressed in cancer cells of
      epithelial origin and in normal tissues during events involving matrix remodeling
      such as the cycling endometrium. We previously observed that inflamed ductule and
      acinar epithelia in the prostate also overexpress matrilysin. The presence of
      infiltrating macrophages in these areas prompted us to determine if factors
      secreted from monocytes could induce matrilysin expression in a human prostatic
      cell line. Conditioned media collected from the monocyte cell line THP-1
      following lipopolysaccharide treatment substantially induced matrilysin protein
      and mRNA expression in LNCaP prostate carcinoma cells. Matrilysin expression in
      LNCaP cells was also induced by recombinant interleukin (IL)-1 (50 pM), but not
      by equimolar concentrations of recombinant tumor necrosis factor-alpha or IL-6.
      The matrilysin-inducing activity of THP-1 conditioned medium was completely
      abrogated by preincubation with a neutralizing antibody to IL-1beta. Transient
      transfection analyses with a chimeric human matrilysin promoter-chloramphenicol
      acetyltransferase reporter construct demonstrated that IL-1beta activates
      transcription through the matrilysin promoter in LNCaP cells. This is the first
      report of matrilysin induction by an inflammatory cytokine in a cell line of
      epithelial origin, and the results suggest a potential mechanism for the
      overexpression of matrilysin in inflamed ducts and glands of the prostate.

PMID- 9162050
TI  - Purification and characterization of Gbetagamma-responsive phosphoinositide 3
      kinases from pig platelet cytosol.
AB  - A G-protein betagamma subunit (Gbetagamma)-responsive phosphoinositide 3-kinase
      (PI 3-kinase) was purified approximately 5000-fold from pig platelet cytosol. The
      enzyme was purified by polyethylene glycol precipitation of the cytosol followed
      by column chromatography on Q-Sepharose fast flow, gel filtration, heparin
      Sepharose, and hydroxyapatite. The major Gbetagamma-responsive PI 3-kinase is
      distinct from p85 containing PI 3-kinase as the activities can be distinguished
      chromatographically and immunologically and is related to p110gamma as it cross
      reacts with anti-p110gamma-specific antibodies. The p110gamma-related PI 3-kinase
      cannot be activated by G-protein alphai/o subunits, and it has an apparent native
      molecular mass of 210 kDa. The p110gamma-related PI 3-kinase phosphorylates
      phosphatidylinositol (PtdIns), phosphatidylinositol 4-phosphate (PtdIns4P), and
      phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). The apparent Km values for
      ATP were found to be 25 microM with PtdIns, 44 microM with PtdIns4P, and 37
      microM with PtdIns(4,5)P2 as the substrate. Gbetagamma subunits did not alter the
      Km of the enzyme for ATP; however, Vmax increased 2-fold with PtdIns as
      substrate, 3.5-fold with PtdIns4P, and 10-fold with PtdIns(4,5)P2. Under basal
      conditions the apparent Km values for lipid substrates were 64, 10, and 15 microM
      for PtdIns, PtdIns4P, and PtdIns(4,5)P2, respectively. In the presence of
      Gbetagamma subunits the dependence of PI 3-kinase activity on the concentrations
      of lipid substrates became complex with the highest level of stimulation
      occurring at high substrate concentration, suggesting that the binding of
      Gbetagamma and lipid substrate (particularly PtdIns(4,5)P2) may be mutually
      cooperative. Wortmannin and LY294002 inhibit the Gbetagamma-responsive PI 3
      kinase activity with IC50 values of 10 nM and 2 microM, respectively. Unlike the
      p85 containing PI 3-kinase in platelets, the p110gamma-related PI 3-kinase is not
      associated with a PtdIns(3,4,5)P3 specific 5-phosphatase. The p85-associated PI 3
      kinase was not activated by Gbetagamma alone but could be synergistically
      activated by Gbetagamma and phosphotyrosyl platelet-derived growth factor
      receptor peptides. This may represent a form of coincidence detection through
      which the effects of tyrosine kinase and G-protein-linked receptors might be
      coordinated.

PMID- 9162051
TI  - Characterization of chemical inhibitors of brefeldin A-activated mono-ADP
      ribosylation.
AB  - Brefeldin A, a toxin inhibitor of vesicular traffic, induces the selective mono
      ADP-ribosylation of two cytosolic proteins, glyceraldehyde-3-phosphate
      dehydrogenase and the novel GTP-binding protein BARS-50. Here, we have used a new
      quantitative assay for the characterization of this reaction and the development
      of specific pharmacological inhibitors. Mono-ADP-ribosylation is activated by
      brefeldin A with an EC50 of 17.0 +/- 3.1 microg/ml, but not by biologically
      inactive analogs including a brefeldin A stereoisomer. Brefeldin A acts by
      increasing the Vmax of the reaction, whereas it does not influence the Km of the
      enzyme for NAD+ (154 +/- 13 microM). The enzyme is an integral membrane protein
      present in most tissues and is modulated by Zn2+, Cu2+, ATP (but not by other
      nucleotides), pH, temperature, and ionic strength. To identify inhibitors of the
      reaction, a large number of drugs previously tested as blockers of bacterial ADP
      ribosyltransferases were screened. Two classes of molecules, one belonging to the
      coumarin group (dicumarol, coumermycin A1, and novobiocin) and the other to the
      quinone group (ilimaquinone, benzoquinone, and naphthoquinone), rather potently
      and specifically inhibited brefeldin A-dependent mono-ADP-ribosylation. When
      tested in living cells, these molecules antagonized the tubular reticular
      redistribution of the Golgi complex caused by brefeldin A at concentrations
      similar to those active in the mono-ADP-ribosylation assay in vitro, suggesting a
      role for mono-ADP-ribosylation in the cellular actions of brefeldin A.

PMID- 9162052
TI  - Purification and characterization of Fet3 protein, a yeast homologue of
      ceruloplasmin.
AB  - The FET3 gene product of Saccharomyces cerevisiae is an essential component of
      the high affinity iron transport system. Based on FET3 sequence homology to the
      multicopper oxidase family and iron oxidation studies in spheroplasts (De Silva,
      D. M., Askwith, C. C., Eide, D., and Kaplan, J. (1995) J. Biol. Chem. 270, 1098
      1101), it was hypothesized that the Fet3 protein (Fet3p) was a cell surface
      ferroxidase. To further characterize the protein, we have isolated Fet3p from
      yeast membranes and purified the protein to apparent homogeneity. Consistent with
      its localization at the plasma membrane, Fet3p is a glycosylated protein. SDS
      polyacrylamide gel electrophoresis analysis showed that the protein was present
      in two differentially glycosylated forms of approximately 120 and 100 kDa.
      Purified Fet3p is a copper-containing protein that is able to catalyze the
      oxidation of a variety of organic compounds in addition to ferrous iron. Azide
      and metal chelators strongly inhibited enzyme activity. Iron appeared to be the
      best substrate for the enzyme, and the apparent Km for ferrous oxidation was 2
      microM. Interestingly, Fet3p was able to effectively catalyze the incorporation
      of iron onto apotransferrin. We conclude that Fet3p is a ferro-O2-oxidoreductase
      in yeast, homologous to the human plasma protein ceruloplasmin.

PMID- 9162053
TI  - Oligomerization of hamster UDP-GlcNAc:dolichol-P GlcNAc-1-P transferase, an
      enzyme with multiple transmembrane spans.
AB  - Hamster UDP-GlcNAc:dolichol-P GlcNAc-1-P transferase (GPT), which initiates N
      linked glycosylation by catalyzing the synthesis of GlcNAc-P-P-dolichol, has
      multiple transmembrane spans and a catalytic site that probably exists on the
      cytosolic face of the endoplasmic reticulum membrane (Dan, N., Middleton, R. M.,
      and Lehrman, M. A. (1996) J. Biol. Chem. 271, 30717-30725). In this report, we
      demonstrate that GPT forms functional oligomers, probably dimers. Oligomers were
      detected by chemical cross-linking of GPT and by a dominant-negative effect
      caused by co-expression of enzymatically inactive (but properly folded) GPT
      mutants. The GPT mutants had no effect on two other dolichol-P-dependent
      endoplasmic reticulum enzymes. Mixing experiments indicated that mature GPT was
      competent for oligomerization. Oligomerization appeared to be favored in
      detergent extracts compared with intact microsomes. Detergent treatments were
      found to prevent, rather than promote, nonspecific aggregation of GPT. These
      results demonstrate that GPT subunits can physically interact and influence each
      other. The implications of oligomerization for enzyme function are discussed.
      From these results, we conclude that GPT is one of a very small number of
      multitransmembrane span enzymes that can form multimers.

PMID- 9162054
TI  - Two oligomeric forms of plasma ficolin have differential lectin activity.
AB  - Ficolins are plasma proteins with binding activity for carbohydrates, elastin,
      and corticosteroids. The ficolin polypeptide has a collagen-like domain that
      presumably brings three subunits together in a triple helical rod, a C-terminal
      fibrinogen-like domain (fbg) similar to that of tenascin, which presumably has
      the binding activities, and a small N-terminal domain that we find to be the
      primary site for forming the ficolin oligomer. By sedimentation equilibrium we
      determined that the main plasma form, which we call big ficolin, had mass of
      827,000 Da, consistent with 24 subunits. Little ficolin, about half this size,
      was obtained after binding to a GlcNAc affinity column. Electron microscopy of
      little ficolin showed a parachute-like structure, with a small globe at one end,
      corresponding to the 12 N-terminal domains, and the fbg domains clustered
      together at the ends of the collagen rods. Big ficolin was formed by the face to
      face fusion of the fbg domains of two little ficolins, leaving the rods and N
      terminal domains projecting at opposite ends. Little ficolin maintained a high
      affinity for the GlcNAc column, and big ficolin had a low affinity or none. The
      binding sites for ligands may be obscured in this big ficolin oligomer, providing
      a regulation of their activity.

PMID- 9162055
TI  - Differential activity of progesterone and glucocorticoid receptors on mouse
      mammary tumor virus templates differing in chromatin structure.
AB  - In vivo, transcription factors interact with promoters having complex
      nucleoprotein structures. The transiently expressed progesterone receptor (PR)
      efficiently activates a transfected mouse mammary tumor virus (MMTV) promoter but
      is a poor activator of the MMTV promoter when it acquires an ordered chromatin
      structure as an endogenous, replicating gene. We show that the deficiency in PR
      activity is not due to insufficient expression of either B or A isoforms or
      competition between the two types of MMTV templates. Rather, this deficiency
      reflects an inability to induce the chromatin remodeling event that is required
      for activation of the replicated MMTV template. To determine whether this
      characteristic is common to transiently expressed steroid receptors or specific
      to the PR, we examined the activity of transiently expressed glucocorticoid (GR)
      receptor. Unlike the PR, the transiently expressed GR is an effective activator
      of both MMTV templates and efficiently induces the necessary chromatin remodeling
      event at the replicated template. These results indicate that the GR and PR have
      unique requirements for activation of promoters with ordered chromatin structure.
      These differences may provide a mechanism for establishing target gene
      specificity in vivo for steroid receptors that recognize and bind to identical
      DNA sequences.

PMID- 9162056
TI  - Evidence that the integrin beta3 and beta5 subunits contain a metal ion-dependent
      adhesion site-like motif but lack an I domain.
AB  - The amino-terminal domain of each integrin beta subunit is hypothesized to
      contain an ion binding site that is key to cell adhesion. A new hypothesis
      regarding the structure of this site is suggested by the crystallization of the I
      domains of the integrin alphaL and alphaM subunits (Lee, J.-O., Rieu, P.,
      Arnaout, M. A., and Liddington, R. (1995) Cell 80, 631-638; Qu, A., and Leahy, D.
      J. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 10277-10281). In those proteins, an
      essential metal ion is bound by a metal ion-dependent adhesion site (MIDAS). The
      MIDAS is presented at the apex of a larger protein module called an I domain. The
      metal ligands in the MIDAS can be separated into three distantly spaced clusters
      of oxygenated residues. These three coordination sites also appear to exist in
      the integrin beta3 and beta5 subunits. Here, we examined the putative metal
      binding site within beta3 and beta5 using site-directed mutagenesis and ligand
      binding studies. We also investigated the fold of the domain containing the
      putative metal binding site using the PHD structural algorithm. The results of
      the study point to the similarity between the integrin beta subunits and the
      MIDAS motif at two of three key coordination points. Importantly though, the
      study failed to identify a residue in either beta subunit that corresponds to the
      second metal coordination group in the MIDAS. Moreover, structural algorithms
      indicate that the fold of the beta subunits is considerably different than the I
      domains. Thus, the integrin beta subunits appear to present a MIDAS-like motif in
      the context of a protein module that is structurally distinct from known I
      domains.

PMID- 9162057
TI  - Transcription factor AP-2 controls transcription of the human transforming growth
      factor-alpha gene.
AB  - The epidermal growth factor receptor is vital for normal development and plays a
      role in oncogenesis. The level of activation of this receptor by transforming
      growth factor-alpha (TGF-alpha) is controlled, in part, by the rate of
      transcription of the TGF-alpha gene. In the characterization of the proximal TGF
      alpha promoter by DNase I footprinting, a 43-base pair element (-88 to -130
      relative to the transcription start site), designated TalphaRE I, was found that
      was specifically protected by nuclear proteins from human mammary carcinoma
      MDA468 cells. TalphaRE I was essential for the maximal expression of the TGF
      alpha gene as indicated by deletion and mutagenesis analyses. TalphaRE I consists
      of two cis-acting elements, a proximal regulatory element (PRE, -89 to -103) and
      a distal regulatory element (DRE, -121 to -128). Both elements were able to form
      specific complexes with protein from MDA468 cell nuclear extracts and are
      necessary for the full activity of the entire 1.1-kilobase pair TGF-alpha
      promoter. Competition and antibody studies determined that the DRE contains a
      binding site for the transcription factor AP-2, while the protein that binds to
      the PRE has yet to be identified. When linked upstream to the heterologous herpes
      simplex thymidine kinase promoter, the TalphaRE I enhanced transcription up to 11
      fold in MDA468 cells. Cotransfection of an AP-2 expression vector was able to
      activate transcription from the TalphaREI-TK construct in a DRE-dependent manner.
      These results further our understanding of how TGF-alpha transcription is
      regulated.

PMID- 9162058
TI  - Resistance of gammaA/gamma' fibrin clots to fibrinolysis.
AB  - Elevated plasma fibrinogen levels are a major risk factor for thrombosis. This
      report shows two mechanisms by which fibrinogen can affect the fibrinolysis rate
      in vitro and thus may lead to thrombosis. First, the lysis rate of fibrin
      decreases as the initial concentration of fibrinogen increases. Second, a minor
      variant form of fibrinogen decreases the rate of fibrinolysis. This variant,
      gammaA/gamma' fibrinogen, has one altered gamma chain and is known to bind to
      factor XIII zymogen. In a fibrinolysis assay containing purified thrombin,
      fibrinogen, tissue-type plasminogen activator, and plasminogen, clots from
      gammaA/gammaA and gammaA/gamma' fibrinogen lysed at similar rates. However, when
      factor XIII was added, slower lysis was seen in gammaA/gamma' fibrin clots when
      compared with gammaA/gammaA fibrin clots. A D-dimer agglutination assay showed
      that the gammaA/gamma' clots were more highly cross-linked than the gammaA/gammaA
      clots. The lysis rates of gammaA/gamma' clots were similar to gammaA/gammaA clots
      in the presence of N-ethylmaleimide, a specific inhibitor of factor XIIIa. The
      gammaA/gamma' fibrin clots made in the presence of factor XIII showed increased
      proteolytic resistance to both plasmin and trypsin. Clots made from
      afibrinogenemic plasma reconstituted with gammaA/gamma' fibrinogen also showed
      significant resistance to lysis compared with gammaA/gammaA fibrinogen. These
      data demonstrate gammaA/gamma' fibrin is resistant to fibrinolysis, possibly as a
      result of concentrating factor XIII on the clot. The total fibrinogen
      concentration and the amount of gammaA/gamma' fibrinogen increase clot stability
      in vitro and thus may contribute independently to the risk of thrombosis in
      humans.

PMID- 9162059
TI  - Metalloregulatory properties of the ArsD repressor.
AB  - The plasmid-encoded arsenical resistance (ars) operon of plasmid R773 produces
      resistance to trivalent and pentavalent salts of the metalloids arsenic and
      antimony in cells of Escherichia coli. The first two genes in the operon, arsR
      and arsD, were previously shown to encode trans-acting repressor proteins. ArsR
      controls the basal level of expression of the operon, while ArsD controls maximal
      expression. Thus, action of the two repressors form a homeostatic regulatory
      circuit that maintains the level of ars expression within a narrow range. In this
      study, we demonstrate that ArsD binds to the same site on the ars promoter
      element as ArsR but with 2 orders of magnitude lower affinity. The results of gel
      shift assays demonstrate that ArsD is released from the ars DNA promoter by
      phenylarsine oxide, sodium arsenite, and potassium antimonyl tartrate (in order
      of effectiveness), the same inducers to which ArsR responds. Using the quenching
      of intrinsic tryptophan fluorescence to measure the affinity of the repressor for
      inducers, apparent Kd values for Sb(III) and As(III) of 2 and 60 microM,
      respectively, were obtained. These results demonstrate that the arsR-arsD pair
      provide a sensitive mechanism for sensing a wide range of environmental heavy
      metals.

PMID- 9162060
TI  - Steroidogenic factor-1 is an essential transcriptional activator for gonad
      specific expression of promoter I of the rat prolactin receptor gene.
AB  - The expression of the prolactin receptor is under the control of two putative
      tissue-specific (PI, gonads; PII, liver) and one common (PIII) promoters (Hu, Z.
      Z., Zhuang, L., and Dufau, M. L. (1996) J. Biol. Chem. 271, 10242-10246). The
      three promoter regions were co-localized to the rat chromosomal locus 2ql6, in
      the order 5'-PIII-PI-PII-3'. To investigate the mechanisms of gonad-specific
      utilization of PI, the promoter domain, regulatory cis-elements, and trans
      factors were identified in gonadal cells. The promoter domain localized to the
      152-base pair 5' of the transcriptional start site at -549 is highly active in
      gonadal cells but has minimal activity in hepatoma cells. It contains a
      steroidogenic factor 1 (SF-1) element (-668) that binds the SF-1 protein of
      nuclear extracts from gonadal cells and is essential for promoter activation. A
      CCAAT box (-623) contributes minimally to basal activity in the absence of the SF
      1 element, and two adjacent TATA-like sequences act as inhibitory elements. Thus,
      PI belongs to a class of TATA-less/non-initiator gene promoters. These findings
      demonstrate an essential role for SF-1 in transcriptional activation of promoter
      I of the prolactin receptor gene, which may explain the tissue-specific
      expression of PI in the gonads but not in the liver and the mammary gland.

PMID- 9162061
TI  - A newly identified member of the tumor necrosis factor receptor superfamily with
      a wide tissue distribution and involvement in lymphocyte activation.
AB  - The tumor necrosis factor receptor (TNFR) superfamily consists of approximately
      10 characterized members of human proteins. We have identified a new member of
      the TNFR superfamily, TR2, from a search of an expressed sequence tag data base.
      cDNA cloning and Northern blot hybridization demonstrated multiple mRNA species,
      of which a 1.7-kilobase form was most abundant. However, TR2 is encoded by a
      single gene which, maps to chromosome 1p36.22-36.3, in the same region as several
      other members of the TNFR superfamily. The most abundant TR2 open reading frame
      encodes a 283-amino acid single transmembrane protein with a 36-residue signal
      sequence, two perfect and two imperfect TNFR-like cysteine-rich domains, and a
      short cytoplasmic tail with some similarity to 4-1BB and CD40. TR2 mRNA is
      expressed in multiple human tissues and cell lines and shows a constitutive and
      relatively high expression in peripheral blood T cells, B cells, and monocytes. A
      TR2-Fc fusion protein inhibited a mixed lymphocyte reaction-mediated
      proliferation suggesting that the receptor and/or its ligand play a role in T
      cell stimulation.

PMID- 9162062
TI  - Thermophilin 13, a nontypical antilisterial poration complex bacteriocin, that
      functions without a receptor.
AB  - A novel broad host range antimicrobial substance, Thermophilin 13, has been
      isolated and purified from the growth medium of Streptococcus thermophilus.
      Thermophilin 13 is composed of the antibacterial peptide ThmA (Mr of 5776) and
      the enhancing factor ThmB (Mr of 3910); the latter peptide increased the activity
      of ThmA approximately 40 x. Both peptides are encoded by a single operon, and an
      equimolar ratio was optimal for Thermophilin 13 activity. Despite the
      antilisterial activity of Thermophilin 13, neither ThmA nor ThmB contain the
      YGNGV-C consensus sequence of Listeria-active peptides, and post-translational
      modifications comparable to that in the lantibiotics are also absent. Mass
      spectrometry did reveal the apparent oxidation of methionines in ThmA, which
      resulted in a peptide that could not be enhanced any longer by ThmB, whereas the
      intrinsic bactericidal activity was normal. Thermophilin 13 dissipated the
      membrane potential and the pH gradient in liposomes, and this activity was
      independent of membrane components from a sensitive strain (e.g. lipid or
      proteinaceous receptor). Models of possible poration complexes formed are
      proposed on the basis of sequence comparisons, structure predictions, and the
      functional analysis of Thermophilin 13.

PMID- 9162063
TI  - The multiple cpb cysteine proteinase genes of Leishmania mexicana encode
      isoenzymes that differ in their stage regulation and substrate preferences.
AB  - The cpb genes of Leishmania mexicana encode stage-regulated, cathepsin L-like
      cysteine proteinases that are leishmanial virulence factors. Field inversion gel
      electrophoresis and genomic mapping indicate that there are 19 cpb genes arranged
      in a tandem array. Five genes from the array have been sequenced and their
      expression analyzed. The first two genes, cpb1 and cpb2, differ significantly
      from the remaining 17 copies (cpb3-cpb19) in that: 1) they are expressed
      predominantly in metacyclic promastigotes (the form in the insect vector which is
      infective to mammalian macrophages) rather than amastigotes (the form that
      parasitizes mammals); 2) they encode enzymes with a truncation in the COOH
      terminal extension, an unusual feature of these cysteine proteinases of
      trypanosomatids. Transfection of cpb1 into a cpb null mutant resulted in
      expression of an active enzyme that was shown by immunogold labeling with anti
      CPB antibodies to be targeted to large lysosomes. This demonstrates that the 100
      amino acid COOH-terminal extension is not essential for the activation or
      activity of the enzyme or for its correct intracellular trafficking. Transfection
      into the cpb null mutant of different copies of cpb and analysis of the phenotype
      of the lines showed that individual isoenzymes differ in their substrate
      preferences and ability to restore the loss of virulence associated with the null
      mutant. Comparison of the predicted amino acid sequences of the isoenzymes
      implicates five residues located in the mature domain (Asn18, Asp60, Asn61,
      Ser64, and Tyr84) with differences in the activities of the encoded isoenzymes.
      The results suggest that the individual isoenzymes have distinct roles in the
      parasite's interaction with its host. This complexity reflects the adaptation of
      cathepsin L-like cysteine proteinases to diverse functions in parasitic protozoa.

PMID- 9162064
TI  - Strikingly different localization of galectin-3 and galectin-4 in human colon
      adenocarcinoma T84 cells. Galectin-4 is localized at sites of cell adhesion.
AB  - Two beta-galactoside-binding proteins were found to be prominently expressed in
      the human colon adenocarcinoma T84 cell line. Cloning and sequencing of one, a 36
      kDa protein, identified it as the human homolog of galectin-4, a protein
      containing two carbohydrate binding domains and previously found only in the
      epithelial cells of the rat and porcine alimentary tract. The other, a 29-kDa
      protein, is galectin-3, containing a single carbohydrate binding domain,
      previously found in a number of different cell types including human intestinal
      epithelium. Despite the marked similarities in the carbohydrate binding domains
      of these two galectins, their cellular distribution patterns are strikingly
      different and vary with cellular conditions. In confluent T84 cells, galectin-4
      is mostly cytosolic and concentrated at the basal membrane, whereas galectin-3
      tends to be concentrated in large granular inclusions mostly at the apical
      membrane. In subconfluent T84 cells, each galectin is distributed to specific
      domains of lamellipodia, with galectin-4 concentrated in the leading edge and
      galectin-3 more proximally. Such different localization of galectins-4 and -3
      within T84 cells implies different targeting mechanisms, ligands, and functions.
      The localization of galectin-4 suggests a role in cell adhesion which is also
      supported by the ability of immobilized recombinant galectin-4 to stimulate
      adhesion of T84 cells.

PMID- 9162065
TI  - Specific hammerhead ribozyme-mediated cleavage of mutant N-ras mRNA in vitro and
      ex vivo. Oligoribonucleotides as therapeutic agents.
AB  - Two hammerhead ribozymes targeted to point mutations in codon 13 of the N-ras
      oncogene were synthesized and their catalytic activity and substrate specificity
      evaluated in vitro and ex vivo. In vitro studies showed that these ribozymes were
      specific for the oncogenic form of N-ras, since cleavage was observed only in a
      849-nucleotide-long transcript containing mutant but not wild-type N-ras
      sequences. For the ex vivo studies, the ribozymes were 2'-modified to protect
      them against degradation by nucleases. 2'-Fluoro-2'-deoxyuridine/cytidine
      substituted ribozymes were nearly as active as their unmodified counterparts, but
      had a prolonged stability in cell culture supernatant containing fetal calf
      serum. The stability of the modified ribozymes increased by introduction of
      terminal phosphorothioates groups without significant influence in their
      catalytic efficiency. A sensitive assay based on the use of N-ras/luciferase
      fusion genes as a reporter system was established to detect ribozyme-mediated
      cleavage in HeLa cells. A reduction of nearly 60% in luciferase activity was
      observed in cells expressing mutant but not wild-type N-ras/luciferase fusion
      transcripts. Moreover, cleavage of N-ras transcripts in HeLa cells was directly
      confirmed by a semi-quantitative RT-PCR assay.

PMID- 9162066
TI  - The evolutionary pressure to inactivate. A subclass of synaptotagmins with an
      amino acid substitution that abolishes Ca2+ binding.
AB  - Synaptotagmin I is a Ca2+-binding protein of synaptic vesicles that serves as a
      Ca2+ sensor for neurotransmitter release and was the first member found of a
      large family of trafficking proteins. We have now identified a novel
      synaptotagmin, synaptotagmin XI, that is highly expressed in brain and at lower
      levels in other tissues. Like other synaptotagmins, synaptotagmin XI has a single
      transmembrane region and two cytoplasmic C2-domains but is most closely related
      to synaptotagmin IV with which it forms a new subclass of synaptotagmins. The
      first C2-domain of synaptotagmin I (the C2A-domain) binds phospholipids as a
      function of Ca2+ and contains a Ca2+-binding site, the C2-motif, that binds at
      least two Ca2+ ions via five aspartate residues and is conserved in most C2
      domains (Shao, X., Davletov, B., Sutton, B., Sudhof, T. C., Rizo, J. R. (1996)
      Science 273, 248-253). In the C2A-domains of synaptotagmins IV and XI, however,
      one of the five Ca2+-binding aspartates in the C2-motif is substituted for a
      serine, suggesting that these C2-domains do not bind Ca2+. To test this, we
      produced recombinant C2A-domains from synaptotagmins IV and XI with either wild
      type serine or mutant aspartate in the C2-motif. Circular dichroism showed that
      Ca2+ stabilizes both mutant but not wild type C2-domains against temperature
      induced denaturation, indicating that the mutations restore Ca2+-binding to the
      wild type C2-domains. Furthermore, wild type C2A-domains of synaptotagmins IV and
      XI exhibited no Ca2+-dependent phospholipid binding, whereas mutant C2A-domains
      bound phospholipids as a function of Ca2+ similarly to wild type synaptotagmin I.
      These experiments suggest that a class of synaptotagmins was selected during
      evolution in which the Ca2+-binding site of the C2A-domain was inactivated by a
      single point mutation. Thus, synaptotagmins must have Ca2+-independent functions
      as well as Ca2+-dependent functions that are selectively maintained in distinct
      members of this gene family.

PMID- 9162067
TI  - Differential signaling after beta1 integrin ligation is mediated through binding
      of CRKL to p120(CBL) and p110(HEF1).
AB  - CRKL is an SH2-SH3-SH3 adapter protein that is a major substrate of the BCR/ABL
      oncogene. The function of CRKL in normal cells is unknown. In cells transformed
      by BCR/ABL we have previously shown that CRKL is associated with two focal
      adhesion proteins, tensin and paxillin, suggesting that CRKL could be involved in
      integrin signaling. In two hematopoietic cell lines, MO7e and H9, we found that
      CRKL rapidly associates with tyrosine-phosphorylated proteins after cross-linking
      of beta1 integrins with fibronectin or anti-beta1 integrin monoclonal antibodies.
      The major tyrosine-phosphorylated CRKL-binding protein in the megakaryocytic MO7e
      cells was identified as p120(CBL), the cellular homolog of the v-Cbl oncoprotein.
      However, in the lymphoid H9 cell line, the major tyrosine-phosphorylated CRKL
      binding protein was p110(HEF1). In both cases, this binding was mediated by the
      CRKL SH2 domain. Interestingly, although both MO7e and H9 cells express p120(CBL)
      and p110(HEF1), beta1 integrin cross-linking induces tyrosine phosphorylation of
      p120(CBL) (but not p110(HEF1)) in MO7e cells and of p110(HEF1) (but not
      p120(CBL)) in H9 cells. In both cell types, CRKL is constitutively complexed to
      C3G, SOS, and c-ABL through its SH3 domains, and the stoichiometry of these
      complexes does not change upon integrin ligation. Thus, in different cell types
      CRKL and its SH3-associated proteins may form different multimeric complexes
      depending on whether p120(CBL) or p110(HEF1) is tyrosine-phosphorylated after
      integrin ligation. The shift in association of CRKL and its SH3-associated
      proteins from p120(CBL) to p110(HEF1) could contribute to different functional
      outcomes of "outside-in" integrin signaling in different cells.

PMID- 9162068
TI  - Calcium binding, but not a calcium-myristoyl switch, controls the ability of
      guanylyl cyclase-activating protein GCAP-2 to regulate photoreceptor guanylyl
      cyclase.
AB  - Guanylyl cyclase-activating protein 2 (GCAP-2) is a recoverin-like calcium
      binding protein that regulates photoreceptor guanylyl cyclase (RetGC) (Dizhoor,
      A. M., and Hurley, J. B. (1996) J. Biol. Chem. 271, 19346-19350). It was reported
      that myristoylation of a related protein, GCAP-1, was critical for its affinity
      for RetGC (Frins, S., Bonigk, W., Muller, F., Kellner, R., and Koch, K.-W. (1996)
      J. Biol. Chem. 271, 8022-8027). We demonstrate that the N terminus of GCAP-2,
      like those of other members of the recoverin family of Ca2+-binding proteins, is
      fatty acylated. However, unlike other proteins of this family, more GCAP-2 is
      present in the membrane fraction at low Ca2+ than at high Ca2+ concentrations. We
      investigated the role of the N-terminal fatty acyl residue in the ability of GCAP
      2 to regulate RetGCs. Myristoylated or nonacylated GCAP-2 forms were expressed in
      Escherichia coli. Wild-type GCAP-2 and the Gly2 --> Ala2 GCAP-2 mutant, which is
      unable to undergo N-terminal myristoylation, were also expressed in mammalian
      HEK293 cells. We found that compartmentalization of GCAP-2 in photoreceptor outer
      segment membranes is Ca2+- and ionic strength-sensitive, but it does not require
      the presence of the fatty acyl group and does not necessarily directly reflect
      GCAP-2 interaction with RetGC. The lack of myristoylation does not significantly
      affect the ability of GCAP-2 to stimulate RetGC. Nor does it affect the ability
      of the Ca2+-loaded form of GCAP-2 to compete with the GCAP-2 mutant that
      constitutively activates RetGC. We conclude that while Ca2+ binding plays a major
      regulatory role in GCAP-2 function, it does not operate through a calcium
      myristoyl switch similar to the one found in recoverin.

PMID- 9162069
TI  - Role of the vav proto-oncogene product (Vav) in erythropoietin-mediated cell
      proliferation and phosphatidylinositol 3-kinase activity.
AB  - The vav proto-oncogene product (Vav), which is specifically expressed in
      hematopoietic cells, contains multiple structural motifs commonly used by
      intracellular signaling molecules. Although a variety of stimuli including
      erythropoietin (Epo) have been shown to tyrosine phosphorylate Vav, little is
      known about the Vav signal transduction pathway. Here, we have investigated the
      role of Vav in the Epo signaling pathway by characterizing its interaction with
      other proteins, using the human Epo-responsive cell line, F-36P.
      Immunoprecipitation and immunoblot analyses have demonstrated that Vav was
      associated with the Epo receptor (EpoR) in an Epo-independent manner and was
      tyrosine-phosphorylated after Epo stimulation. Furthermore, two phosphotyrosine
      proteins (pp70 and pp100) co-immunoprecipitated with the regulatory subunit of
      phosphatidylinositol 3-kinase (PI3-kinase) (p85) were identified as EpoR and Vav,
      respectively. The interaction between Vav and p85 was shown to be mediated
      through the SH2 domains of p85 by an in vitro binding assay and confirmed by the
      presence of in vitro PI3-kinase activity associated with Vav. Treatment of the
      cells with antisense-vav and -p85 abrogated Epo-induced cell proliferation and
      PI3-kinase activity. Finally, we found that JAK2 was associated with Vav in vivo
      and that Vav could be tyrosine-phosphorylated by activated JAK2 in vitro. These
      results suggest the possible role of JAK2 for tyrosine phosphorylation of Vav and
      involvement of Vav and PI3-kinase in Epo-induced proliferative signals.

PMID- 9162070
TI  - Paxillin is tyrosine-phosphorylated by and preferentially associates with the
      calcium-dependent tyrosine kinase in rat liver epithelial cells.
AB  - We and others have recently cloned a non-receptor, calcium-dependent tyrosine
      kinase (CADTK; also known as PYK2, CAKbeta, and RAFTK) that shares both overall
      domain structure and 45% amino acid identity with p125(FAK). We have studied the
      signaling, activation, and potential function of these related enzymes in GN4 rat
      liver epithelial cells that express CADTK and p125(FAK) at roughly similar
      levels. p125(FAK) is nearly fully tyrosine-phosphorylated in resting GN4 cells.
      In contrast, while CADTK is not tyrosine-autophosphorylated in untreated cells,
      angiotensin II increases CADTK Tyr(P) by 5-10-fold. With regard to signaling,
      CADTK activation is correlated with stimulation of c-Jun N-terminal kinase and
      p70(S6K) pathways but not with the stimulation of mitogen-activated protein
      kinase or p90(RSK). In this report we assessed the contribution of CADTK and
      p125(FAK) to tyrosine phosphorylation of focal contact proteins. In adherent GN4
      cells, the constitutive activity of p125(FAK) was correlated with basal paxillin,
      tensin, and p130(CAS) tyrosine phosphorylation. A rapid increase in the tyrosine
      phosphorylation of each protein was detected after treatment with angiotensin II
      or other agonists that stimulate CADTK; the prolonged 3-4-fold increase in
      paxillin tyrosine phosphorylation was the most substantial change. In the WB cell
      line that expresses 3-fold less CADTK than GN4 cell line agonist-dependent
      paxillin tyrosine phosphorylation is similarly reduced. Immunoprecipitation of
      CADTK from GN4 cells revealed CADTK. paxillin complexes that persisted in 500 mM
      NaCl but not in 0.1% SDS cell lysis buffer. The complexes were largely
      independent of the tyrosine phosphorylation state of either protein.
      Surprisingly, we did not detect p125(FAK).paxillin complexes in
      immunoprecipitates using either of two p125(FAK) antibodies. When CADTK and
      p125(FAK) were transiently overexpressed in 293(T) cells, both enzymes associated
      with paxillin, but the avidity of CADTK appeared to be greater. In addition, in
      transfected 293(T) cells, complexes between CADTK and another potential
      substrate, p130(CAS), were detected. In summary, in GN4 rat liver epithelial
      cells stimulation of CADTK was highly correlated with paxillin tyrosine
      phosphorylation; in addition, CADTK but not p125(FAK) was complexed to paxillin
      at detectable levels. This suggests that agonist-dependent cytoskeletal changes
      in epithelial cells might proceed, in part, by CADTK-dependent mechanisms.

PMID- 9162071
TI  - Membrane-anchored heparin-binding epidermal growth factor-like growth factor acts
      as a tumor survival factor in a hepatoma cell line.
AB  - Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), which
      belongs to the EGF family, is produced as a membrane-anchored form (pro-HB-EGF)
      and later processed to a soluble form (sHB-EGF). It is known that high expression
      of pro-HB-EGF occurs in hepatoma tissues, although its biological meaning remains
      unknown. We established two types of hepatoma cell lines (AH66tc), which stably
      produce pro-HB-EGF and sHB-EGF, respectively. While sHB-EGF-producing cells (sHB
      AH) showed rapid growth, pro-HB-EGF-producing cells (pHB-AH) showed markedly
      suppressed cell growth as compared with the parental cells. Transforming growth
      factor beta or serum-starved conditions induced apoptosis of mock and sHB-AH as
      well as the parental cells, but not of pHB-AH. The resistance to apoptosis upon
      serum-starved treatment was correlated with an increase in the rate of the G1
      phase in the cell cycle due to up-regulation of the cyclin-dependent kinase
      inhibitor p21. The mechanism underlying this resistance of pHB-AH to apoptosis
      was thought to be related to the prolonged half-life of the EGF receptor followed
      by continuous phosphorylation of the tyrosine residues. These observations
      demonstrate a unique function of pro-HB-EGF that is not observed for the mature
      form and show that pro-HB-EGF may act as a tumor survival factor in hepatoma
      cells.

PMID- 9162072
TI  - SHY1, the yeast homolog of the mammalian SURF-1 gene, encodes a mitochondrial
      protein required for respiration.
AB  - C173 and W125 are pet mutants of Saccharomyces cerevisiae, partially deficient in
      cytochrome oxidase but with elevated concentrations of cytochrome c. Assays of
      electron transport chain enzymes indicate that the mutations exert different
      effects on the terminal respiratory pathway, including an inefficient transfer of
      electrons between the bc1 and the cytochrome oxidase complexes. A cloned gene
      capable of restoring respiration in C173/U1 and W125 is identical to reading
      frame YGR112w of yeast chromosome VII (GenBank Z72897Z72897). The encoded protein
      is homologous to the product of the mammalian SURF-1 gene. In view of the
      homology, the yeast gene has been designated SHY1 (Surf Homolog of Yeast). An
      antibody against the carboxyl-terminal half of Shy1p has been used to localize
      the protein in the inner mitochondrial membrane. Deletion of part of SHY1
      produces a phenotype similar to that of G91 mutants. Disruption of SHY1 at a
      BamHI site, located approximately 2/3 of the way into the gene, has no obvious
      phenotypic consequence. This evidence, together with the ability of a carboxyl
      terminal coding sequence starting from the BamHI site to complement a shy1
      mutant, suggests that the Shy1p contains two domains that can be separately
      expressed to form a functional protein.

PMID- 9162073
TI  - cis-Acting elements and trans-acting proteins in the transcriptional inhibition
      of gonadotropin-releasing hormone gene by human chorionic gonadotropin in
      immortalized hypothalamic GT1-7 neurons.
AB  - We investigated the cis-acting elements and trans-acting proteins required for
      the transcriptional inhibition of the gonadotropin-releasing hormone (GnRH) gene
      by human chorionic gonadotropin (hCG) in GT1-7 neurons. Transient transfection of
      GT1-7 neurons with the 5'-flanking region of the rat GnRH gene-luciferase fusion
      constructs revealed that a 53-base pair (bp) sequence between -126 and -73 bp is
      required for the hCG inhibition. Nuclear extracts from GT1-7 neurons contained
      110- and 95-kDa proteins that formed two complexes with the 53-bp sequence. These
      proteins are not related to Fos, cAMP response element-binding protein, Oct-1, or
      progesterone receptors, and hCG treatment selectively increased the 95-kDa
      protein. DNase I footprinting with GT1-7 cell nuclear extracts protected the -99
      to -79-bp region, which contained a so-called imperfect AP-1 site (-99 to -94 bp)
      and two AT-rich palindromic sequences (-91 to -87 bp and -85 to -81 bp). The
      mutagenesis of the AT-rich regions, but not the AP-1 site, resulted in a loss of
      DNA binding of the 95-kDa protein and the inhibitory effect of hCG. In summary,
      our results are consistent with hCG inducing a 95-kDa trans-acting protein, which
      binds to -91- to -81-bp AT-rich sequences in the 5'-flanking region to inhibit
      the transcription of the GnRH gene.

PMID- 9162074
TI  - Embryonic fibroblasts that are genetically deficient in low density lipoprotein
      receptor-related protein demonstrate increased activity of the urokinase receptor
      system and accelerated migration on vitronectin.
AB  - Low density lipoprotein receptor-related protein (LRP) mediates the endocytosis
      of diverse ligands, including urokinase plasminogen activator (uPA) and its
      receptor, uPAR, which have been implicated in cellular migration. The purpose of
      this study was to determine whether LRP affects cellular migration. Murine
      embryonic fibroblasts (MEF) that are LRP-deficient due to targeted gene
      disruption and exotoxin selection (MEF-2), heterozygous fibroblasts (PEA-10), and
      wild-type fibroblasts (MEF-1) were compared. When cultures were denuded of cells
      in a 1-mm-wide strip, all three cell types migrated into the denuded area. The
      MEF-2 cells migrated nearly twice as rapidly as the MEF-1 cells or PEA-10 cells.
      The difference in migration velocity was duplicated in culture wells that were
      precoated with serum or vitronectin and partially duplicated in wells coated with
      fibronectin but not in wells coated with type I collagen or Matrigel. uPA was
      detected in MEF-2 conditioned medium (CM) at a concentration of 0.30 +/- 0.02 nM,
      which was 13-fold higher than the level detected in MEF-1 CM or PEA-10 CM,
      suggesting one potential mechanism for the enhanced migration of MEF-2 cells.
      uPAR was also increased on MEF-2 cells by 4-5-fold, as determined by PI-PLC
      release, and by 2.5-fold, as determined by a uPA/uPAR activity assay. Mannosamine
      treatment, which down-regulates cell-surface uPAR, decreased MEF-2 migration by
      40% without significantly affecting MEF-1 migration. MEF-2 CM, which is uPA-rich,
      increased the rate of MEF-1 migration, and MEF-1 CM did not. These studies
      demonstrate alterations in cellular migration and in the activity of the uPA/uPAR
      system which accompany complete deficiency of LRP expression in fibroblasts. We
      propose that uPA and uPAR form an autocrine loop for promoting fibroblast
      migration and that LRP counteracts the activity of this system.

PMID- 9162075
TI  - Evidence for the existence of two ATP-sensitive Rb+ occlusion pockets within the
      transmembrane domains of Na+/K+-ATPase.
AB  - A trypsin-digested Na+/K+-ATPase that has lost ATPase activity and about half of
      its protein content retains an essentially intact beta-subunit, the 10
      transmembrane domains of the alpha-subunit, and the full capacity to occlude Na+
      and Rb+ (a congener of K+). When this preparation was incubated at 37 degrees C
      in the absence of Rb+, it lost half of its Rb+ occluding capacity and two-thirds
      of its Na+ occluding capacity. Comparison of the Rb+ occlusion-deocclusion
      kinetics of the digested enzyme before and after partial inactivation indicated
      that (a) the affinities of the labile and the stable halves of occluded Rb+ were
      the same; (b) occlusion and deocclusion rates of the stable pool were lower than
      those of the labile pool; (c) ATP at a low affinity site (K0.5 = 25-300 microM)
      increased deocclusion rate in the stable pool and occlusion rate in the labile
      pool; (d) Na+ increased Rb+ deocclusion rate of the sum of the two pools but not
      that of the stable pool; and (e) occlusion and deocclusion rates of both pools
      were decreased by ouabain. These findings suggest that (a) the peptide complex of
      the digested enzyme contains two distinct but interacting cation occlusion
      pockets, one occluding two Na+ or one Rb+, and the other occluding one Na+ or one
      Rb+; (b) this peptide complex that is devoid of the catalytic ATP site retains an
      allosteric ATP site; and (c) the access channels of the two pockets are regulated
      differently by ATP but similarly by ouabain. Analyses of the gel electrophoretic
      patterns of the digested enzyme and the N termini of the appropriate bands showed
      that inactivation of the labile occlusion pocket was accompanied by 60-70% loss
      of two alpha-fragments containing H3-H4 and H5-H6 transmembrane domains. This and
      the previously established interactions among the transmembrane helices of alpha-
      and beta-subunits suggest that one occlusion pocket is associated with H3-H6
      domains and that the other is located within a complex of beta-subunit and two
      alpha-fragments containing H1-H2 and H7-H10 transmembrane domains.

PMID- 9162076
TI  - Beta-trace gene expression is regulated by a core promoter and a distal thyroid
      hormone response element.
AB  - We isolated and characterized the human beta-Trace protein (betaTP) gene
      promoter. betaTP, also known as prostaglandin D2 synthase, is a lipocalin
      secreted from the choroid plexus and meninges into cerebrospinal fluid. Basal
      transcription of the betaTP gene is directed from a core promoter found within
      the first 325 bases of the 5'-flanking sequence. The betaTP gene promoter is
      responsive to thyroid hormone (3,3',5-triiodothyronine, T3) and efficiently
      repressed by unliganded human thyroid hormone receptor beta (TRbeta). Functional
      analysis of the betaTP promoter in TE671 cells revealed that responsiveness to T3
      occurs in sequences 2.5 kilobase pairs 5' of the start site. Within the hormone
      responsive region we identified a thyroid hormone response element (TRE) located
      from -2576 to -2562 base pairs relative to the transcription start site. The
      betaTP TRE is composed of two directly repeated consensus half-sites separated by
      a 3-base pair space (DR3). The betaTP TRE forms specific complexes with TRbeta.
      We have shown that a gene active in the choroid plexus and meninges is responsive
      to T3. T3 may play a role in the regulated transport of substances into the
      cerebrospinal fluid and ultimately the brain.

PMID- 9162077
TI  - Interleukin-4 and -13 inhibit tumor necrosis factor-alpha mRNA translational
      activation in lipopolysaccharide-induced mouse macrophages.
AB  - The production of tumor necrosis factor-alpha (TNF-alpha) by lipopolysaccharide
      (LPS)-stimulated macrophages can be markedly inhibited by the two closely related
      cytokines, interleukin (IL)-4 and IL-13. To investigate the molecular mechanism
      of this inhibition, we analyzed the effect of the two cytokines on TNF-alpha
      production and TNF-alpha mRNA accumulation in the mouse macrophage cell lines RAW
      264.7 and J774 stimulated by LPS. Whereas LPS-induced TNF-alpha production is
      strongly suppressed by both cytokines, TNF-alpha mRNA accumulation is not
      significantly affected, indicating that IL-4 and IL-13 induce a translational
      repression of TNF-alpha mRNA. Transfection of reporter gene constructs containing
      different regions of the TNF-alpha gene revealed that the inhibitory action of IL
      4 and IL-13 is mediated by the UA-rich sequence present in the TNF-alpha mRNA 3'
      untranslated region.

PMID- 9162078
TI  - Biosynthesis of chondroitin sulfate. Purification of glucuronosyl transferase II
      and use of photoaffinity labeling for characterization of the enzyme as an 80-kDa
      protein.
AB  - A photoaffinity analogue, [beta-32P]5-azido-UDP-GlcA, was used to photolabel the
      enzymes that utilize UDP-GlcA in cartilage microsomes and rat liver microsomes.
      SDS-polyacrylamide gel electrophoresis analysis of photolabeled cartilage
      microsomes, which are specialized in chondroitin sulfate synthesis, showed a
      major radiolabeled band at 80 kDa and other minor radiolabeled bands near 40 and
      60 kDa. Rat liver microsomes, which are enriched for enzymes of detoxification by
      glucuronidation, had a different pattern with multiple major labeled bands near
      50-60 and 35 kDa. To determine that the photolabeled 80-kDa protein is the GlcA
      transferase II, we have purified the enzyme from cartilage microsomes. This
      membrane-bound enzyme, involved in the transfer of GlcA residues to non-reducing
      terminal GalNAc residues of the chondroitin polymer, has now been solubilized,
      stabilized, and then purified greater than 1350-fold by sequential chromatography
      on Q-Sepharose, heparin-Sepharose, and WGA-agarose. The purified enzyme exhibited
      a conspicuous silver-stained protein band on SDS-polyacrylamide gel
      electrophoresis that coincided with the major radiolabeled band of 80 kDa. SDS
      polyacrylamide gel analysis of photoaffinity-labeled active fractions from the Q
      Sepharose, heparin-Sepharose, and WGA-agarose also indicated only the single
      radiolabeled band at 80 kDa. Intensity of photolabeling in each of the fractions
      examined coincided with enzyme activity. The photolabeling of this 80-kDa protein
      was saturable with the photoprobe and could be inhibited by the addition of UDP
      GlcA prior to the addition of the photoprobe. Thus, the photolabeling with [beta
      32P]5-azido-UDP-GlcA has identified the GlcA transferase II as an 80-kDa protein.
      The purified enzyme was capable of transferring good amounts of GlcA residues to
      chondroitin-derived pentasaccharide with negligible transfer to pentasaccharides
      derived from hyaluronan or heparan.

PMID- 9162079
TI  - Activity-dependent expression of parathyroid hormone-related protein (PTHrP) in
      rat cerebellar granule neurons. Requirement of PTHrP for the activity-dependent
      survival of granule neurons.
AB  - To identify genes whose expression is neuronal activity-dependent, we used an
      mRNA differential display technique and discovered that parathyroid hormone
      related protein (PTHrP) is expressed in an activity-dependent manner in primary
      cultures of rat cerebellar granule neurons. PTHrP mRNA was expressed as early as
      1 h by the addition of KCl to a final concentration of 25 mM to the culture
      medium. This expression was induced by Ca2+ influx through voltage-dependent L
      type Ca2+ channels and regulated at the transcriptional step. PTHrP mRNA was
      persistently expressed before and after the time of commitment of granule neurons
      to apoptosis when they are cultured in the presence of 25 mM KCl or both 150
      microM N-methyl-D-aspartic acid and 15 mM KCl, both of which promote the survival
      of these neurons. PTHrP was rapidly secreted into the culture medium in a
      depolarization-dependent manner. Parathyroid hormone/PTHrP receptor mRNA was also
      expressed in the primary cultures, and its expression was up-regulated by KCl
      and/or N-methyl-D-aspartic acid. The addition of anti-PTHrP antiserum to the
      culture medium resulted in a reduction of the activity-dependent survival of the
      granule neurons. These results suggest that PTHrP is involved in an autocrine
      loop and required for the survival of granule neurons.

PMID- 9162080
TI  - Identification of a new pathogen-induced member of the subtilisin-like processing
      protease family from plants.
AB  - By using biochemical, immunological, and molecular strategies we have identified
      and cloned a cDNA encoding a protease from tomato (Lycopersicon esculentum)
      plants (P69B) that is part of a proteolytic system activated in the plant as a
      result of infection with citrus exocortis viroid. This new protease is closely
      related, in terms of amino acid sequence and structural organization, to the
      previously identified pathogenesis-related subtilisin-like protease (Tornero, P.,
      Conejero, V., and Vera, P. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 6332-6337).
      The 745-residue amino acid sequence of P69B begins with a cleavable signal
      peptide, contains a prodomain and a 631-residue mature domain which is homologous
      to the catalytic modules of bacterial subtilisins and eukaryotic Kex2-like
      proteases. Within the catalytic domain, the essential Asp, His, and Ser residues
      that conform the catalytic triad of this family of proteases are conserved in
      P69B. Northern blot and reverse transcriptase-polymerase chain reaction analysis
      demonstrated widespread induced expression of the 2.5-kilobase hybridizing mRNA
      in plant tissues as a consequence of viroid infection. We propose that P69B is a
      member of a complex gene family of plant Kex2/subtilisin-like proteases
      presumably involved in a number of specific proteolytic events activated during
      pathogenesis in plants and that takes place in the extracellular matrix.

PMID- 9162081
TI  - Human tyrosyl-tRNA synthetase shares amino acid sequence homology with a putative
      cytokine.
AB  - To test the hypothesis that tRNATyr recognition differs between bacterial and
      human tyrosyl-tRNA synthetases, we sequenced several clones identified as human
      tyrosyl-tRNA synthetase cDNAs by the Human Genome Project. We found that human
      tyrosyl-tRNA synthetase is composed of three domains: 1) an amino-terminal
      Rossmann fold domain that is responsible for formation of the activated E.Tyr-AMP
      intermediate and is conserved among bacteria, archeae, and eukaryotes; 2) a tRNA
      anticodon recognition domain that has not been conserved between bacteria and
      eukaryotes; and 3) a carboxyl-terminal domain that is unique to the human tyrosyl
      tRNA synthetase and whose primary structure is 49% identical to the putative
      human cytokine endothelial monocyte-activating protein II, 50% identical to the
      carboxyl-terminal domain of methionyl-tRNA synthetase from Caenorhabditis
      elegans, and 43% identical to the carboxyl-terminal domain of Arc1p from
      Saccharomyces cerevisiae. The first two domains of the human tyrosyl-tRNA
      synthetase are 52, 36, and 16% identical to tyrosyl-tRNA synthetases from S.
      cerevisiae, Methanococcus jannaschii, and Bacillus stearothermophilus,
      respectively. Nine of fifteen amino acids known to be involved in the formation
      of the tyrosyl-adenylate complex in B. stearothermophilus are conserved across
      all of the organisms, whereas amino acids involved in the recognition of tRNATyr
      are not conserved. Kinetic analyses of recombinant human and B.
      stearothermophilus tyrosyl-tRNA synthetases expressed in Escherichia coli
      indicate that human tyrosyl-tRNA synthetase aminoacylates human but not B.
      stearothermophilus tRNATyr, and vice versa, supporting the original hypothesis.
      It is proposed that like endothelial monocyte-activating protein II and the
      carboxyl-terminal domain of Arc1p, the carboxyl-terminal domain of human tyrosyl
      tRNA synthetase evolved from gene duplication of the carboxyl-terminal domain of
      methionyl-tRNA synthetase and may direct tRNA to the active site of the enzyme.

PMID- 9162082
TI  - Phosphatidylinositol 3-kinase links the interleukin-2 receptor to protein kinase
      B and p70 S6 kinase.
AB  - Phosphatidylinositol 3-kinase (PI 3-kinase) is activated by the cytokine
      interleukin-2 (IL-2). We have used a constitutively active PI 3-kinase to
      identify IL-2-mediated signal transduction pathways directly regulated by PI 3
      kinase in lymphoid cells. The serine/threonine protein kinase B (PKB)/Akt can act
      as a powerful oncogene in T cells, but its positioning in normal T cell responses
      has not been explored. Herein, we demonstrate that PKB is activated by IL-2 in a
      PI 3-kinase-dependent fashion. Importantly, PI 3-kinase signals are sufficient
      for PKB activation in IL-2-dependent T cells, and PKB is a target for PI 3-kinase
      signals in IL-2 activation pathways. The present study establishes also that PI 3
      kinase signals or PKB signals are sufficient for activation of p70 S6 kinase in T
      cells. PI 3-kinase can contribute to, but is not sufficient for, activation of
      extracellular signal-regulated kinases (Erks) and Erk effector pathways.
      Therefore, PI 3-kinase is a selective regulator of serine/threonine kinase signal
      transduction pathways in T lymphocytes, and this enzyme provides a crucial link
      between the interleukin-2 receptor, the protooncogene PKB, and p70 S6 kinase.

PMID- 9162083
TI  - Ribosome targeting of PKR is mediated by two double-stranded RNA-binding domains
      and facilitates in vivo phosphorylation of eukaryotic initiation factor-2.
AB  - Protein kinase PKR is activated in mammalian cells during viral infection,
      leading to phosphorylation of the alpha subunit of eukaryotic initiation factor-2
      (eIF-2alpha) and inhibition of protein synthesis. This antiviral response is
      thought to be mediated by association of double-stranded RNA (ds-RNA), a by
      product of viral replication, with two ds-RNA-binding domains (DRBDs) located in
      the amino terminus of PKR. Recent studies have observed that expression of
      mammalian PKR in yeast leads to a slow growth phenotype due to
      hyperphosphorylation of eIF-2alpha. In this report, we observed that while DRBD
      sequences are required for PKR to function in the yeast model system, these
      sequences are not required for in vitro phosphorylation of eIF-2alpha. To explain
      this apparent contradiction, we proposed that these sequences are required to
      target the kinase to the translation machinery. Using sucrose gradient
      sedimentation, we found that wild-type PKR was associated with ribosomes,
      specifically with 40 S particles. Deletions or residue substitutions in the DRBD
      sequences blocked kinase interaction with ribosomes. These results indicate that
      in addition to mediating ds-RNA control of PKR, the DRBD sequences facilitate PKR
      association with ribosomes. Targeting to ribosomes may enhance in vivo
      phosphorylation of eIF-2alpha, by providing PKR access to its substrate.

PMID- 9162084
TI  - Platelet endothelial cell adhesion molecule-1 is phosphorylatable by c-Src, binds
      Src-Src homology 2 domain, and exhibits immunoreceptor tyrosine-based activation
      motif-like properties.
AB  - Platelet endothelial cell adhesion molecule-1 (PECAM-1) is 130-kDa member of the
      immunoglobulin gene superfamily that localizes to cell-cell borders of confluent
      endothelial cells and has been shown to play a role in the control of endothelial
      sheet migration and leukocyte transmigration through the endothelium. The
      cytoplasmic tail plays an important role in the modulation of PECAM-1 function.
      Mutation of tyrosine 663 or 686 in the cytoplasmic tail reduces phosphorylation
      and mutation of 686 is associated with a reduction in PECAM-1-mediated inhibition
      of cell migration (1). We have previously noted that these two tyrosine residues
      are surrounded by consensus sequences for Src homology 2 (SH2) domain binding (1,
      2), and the experiments presented explore the potential for PECAM-1-Src and PECAM
      1-SH2 domain interactions. PECAM-1 is more highly phosphorylated in endothelial
      cells overexpressing c-Src, and in in vitro kinase assays, c-Src can
      phosphorylate a glutathione S-transferase (GST)-PECAM cytoplasmic tail fusion
      protein. The phosphorylated fusion protein associates with the bead-bound c-Src.
      This association appears to be mediated by Src-SH2 domain, because PECAM-1 can be
      precipitated by a GST-Src-SH2 affinity matrix. The binding to the GST-Src-SH2
      affinity matrix correlates directly with the level of PECAM-1 phosphorylation,
      because more PECAM-1 is precipitated from c-Src overexpressors and from wild-type
      rather than Tyr663 --> Phe and Tyr686 --> Phe mutant PECAM-1 expressors. Yet
      unidentified phosphoproteins can also be coimmunoprecipitated with wild-type but
      not mutant PECAM-1. Finally, we note the similarity of the PECAM-1 cytoplasmic
      domain sequence to the immunoreceptor tyrosine-based activation motif. Our data
      begin to delineate how tyrosines 663 and 686 may play a role in mediating PECAM-1
      signal transduction.

PMID- 9162085
TI  - Docked secretory vesicles undergo Ca2+-activated exocytosis in a cell-free
      system.
AB  - The Ca2+-activated fusion of secretory vesicles with the plasma membrane
      responsible for regulated neurotransmitter and hormone secretion has previously
      been studied in permeable neuroendocrine cells, where requirements for ATP and
      cytosolic proteins were identified. As reported here, Ca2+-activated fusion
      mechanisms are also preserved following cell homogenization. The release of
      norepinephrine (NE) and other vesicle constituents from a PC12 cell membrane
      fraction was activated by micromolar Ca2+ (EC50 approximately 3 microM) and
      exhibited a dependence upon MgATP and cytosol. Ca2+-dependent NE release was
      inhibited by botulinum neurotoxins and by CAPS (Ca2+-dependent activator protein
      for secretion) antibody implying that syntaxin, synaptobrevin, SNAP-25
      (synaptosomal-associated protein of 25 kDa), and CAPS are required for regulated
      exocytosis in this system. The exocytosis-competent membrane fraction consisted
      of rapidly sedimenting dense core vesicles associated with plasma membrane
      fragments. Free vesicles did not release NE either in the absence or presence of
      plasma membranes, indicating that only docked vesicles were competent for
      exocytosis under the reconstitution conditions used. A cell-free system for Ca2+
      activated fusion will facilitate studies on the roles of essential proteins such
      as syntaxin, synaptobrevin, SNAP-25, and CAPS that act at post-docking steps in
      the regulated exocytotic pathway.

PMID- 9162086
TI  - Identification of a palindromic sequence that is responsible for the up
      regulation of NAPDH-ferredoxin reductase in a ferredoxin I deletion strain of
      Azotobacter vinelandii.
AB  - Azotobacter vinelandii ferredoxin I (AvFdI) is one member of a class of 7Fe
      ferredoxins found in a variety of organisms that are all capable of aerobic
      growth. Disruption of the fdxA gene, which encodes AvFdI, leads to overexpression
      of its redox partner, NADPH-ferredoxin reductase (FPR). In this study the
      mechanism of FdI-mediated regulation of FPR was investigated. Northern analysis
      has shown that regulation is at the level of fpr transcription, the start site
      for transcription has been identified, and it is preceded by a canonical sigma 70
      type bacterial promoter. Gel mobility shift assays show that there is a putative
      regulatory protein in A. vinelandii that binds specifically upstream of the -35
      region. That protein is not AvFdI. A palindromic sequence was identified as a
      putative binding site, and randomization of that sequence completely eliminates
      binding of the putative regulatory protein. A luciferase reporter gene was placed
      under control of the A. vinelandii fpr promoter and introduced into wild type and
      FdI- strains of A. vinelandii. Luciferase activity was enhanced 7-fold in the FdI
      mutant relative to the wild type. Alteration of the palindromic sequence reduced
      the luciferase levels in the FdI- strain to those of the wild type, demonstrating
      that FdI regulates FPR through the palindrome and that the reaction is an
      activation rather than a repression. The identified palindrome is approximately
      50% identical to the SoxS binding site upstream of Escherichia coli fpr,
      suggesting that A. vinelandii may have a SoxS-like regulatory system and that the
      function of FdI might be to specifically inactivate that system.

PMID- 9162087
TI  - K- and N-Ras are geranylgeranylated in cells treated with farnesyl protein
      transferase inhibitors.
AB  - The association of mutant forms of Ras protein with a variety of human cancers
      has stimulated intense interest in therapies based on inhibiting oncogenic Ras
      signaling. Attachment of Ras proteins to the plasma membrane is required for
      effective Ras signaling and is initiated by the enzyme farnesyl protein
      transferase. We found that in the presence of potent farnesyl protein transferase
      inhibitors, Ras proteins in the human colon carcinoma cell line DLD-1 were
      alternatively prenylated by geranylgeranyl transferase-1. When H-Ras, N-Ras, K
      Ras4A, and K-Ras4B were expressed individually in COS cells, H-Ras prenylation
      and membrane association were found to be uniquely sensitive to farnesyl
      transferase inhibitors; N- and K-Ras proteins incorporated the geranylgeranyl
      isoprene group and remained associated with the membrane fraction. The
      alternative prenylation of N- and K-Ras has significant implications for our
      understanding of the mechanism of action of farnesyl protein transferase
      inhibitors as anti-cancer chemotherapeutics.

PMID- 9162088
TI  - The role of alpha- and epsilon-amino groups in the glycation-mediated cross
      linking of gammaB-crystallin. Study of three site-directed mutants.
AB  - In the previous report we demonstrated that gammaB-crystallin is glycated
      predominantly at the N-terminal alpha-amino group (Casey, E. B., Zhao, H. R., and
      Abraham, E. C. (1995) J. Biol. Chem. 270, 20781-20786). To investigate the
      possible role of alpha- and epsilon-amino groups of gammaB-crystallin in
      glycation-mediated cross-linking, Lys-2 or Lys-163, or both, were mutated to
      threonine by site-directed mutagenesis in bovine gammaB-crystallin cDNA. Wild
      type and mutant gammaB-crystallins were expressed in Escherichia coli cells.
      Cross-linking studies were performed by incubating wild type and mutant gammaB
      crystallins with glyceraldehyde, ribose, and galactose followed by SDS
      polyacrylamide gel electrophoresis under reducing conditions. When both of the
      lysines of gammaB-crystallin were mutated to threonines (gammaB-K2T/K163T), the
      quantity of cross-linked products was greatly reduced, indicating that, despite
      the fact that the alpha-amino group is a major glycated site, epsilon-amino
      groups play a predominant role in cross-linking. Therefore, cross-linking ability
      depends not only upon the level of glycation but also upon which amino group is
      glycated. Steric hindrance may decrease the cross-linking ability of the alpha
      amino group. Our results also show that Lys-2 and Lys-163 play almost equal roles
      in cross-linking of gammaB-crystallin. By incubating carbonic anhydrase, a
      protein with a blocked N terminus, and our novel "no lysine" gammaB (gammaB
      K2T/K163T) with sugar, we were able to show for the first time that significant
      cross-linking occurs between lysines and non-lysine sites. The fact that
      pentosidine and imidazolysine, formed from ribose and methylglyoxal,
      respectively, were present in the cross-linked gammaB-crystallins revealed the
      existence of Lys-Arg and Lys-Lys cross-linking.

PMID- 9162090
TI  - On the mechanism of the antifibrinolytic activity of plasma carboxypeptidase B.
AB  - The precursor of plasma carboxypeptidase B (pCPB) also known as thrombin
      activable fibrinolysis inhibitor can be converted by thrombin to an active enzyme
      capable of eliminating C-terminal Lys- and Arg-residues from proteins. The
      activation is about 1000-fold more efficient in the presence of thrombomodulin
      (TM). We investigated the antifibrinolytic potency of maximally activated pCPB in
      plasma and explored the antifibrinolytic mechanism of pCPB. During clotting of
      plasma in the presence of 3.3 NIH units/ml thrombin and 1 microg/ml soluble TM,
      more than 80% pro-pCPB was converted into the active form causing an increase of
      plasma carboxypeptidase activity from 100 units/liter (constitutive activity
      ascribed to plasma carboxypeptidase N) to 430 units/liter as measured with
      furoylacroleyl-alanyl-arginine substrate. Under these conditions, lysis of a
      plasma clot induced by a range of tissue-type plasminogen activator (t-PA)
      concentrations (0.2-2 microg/ml) was retarded more than 4-fold. A considerable
      retardation of fibrinolysis was observed upon addition of as little as 12 ng/ml
      soluble TM, a concentration comparable with physiological concentrations of
      soluble TM in human plasma. The presence of Ca2+ appeared to be a critical
      requirement for effective activation of pro-pCPB by thrombin-TM in plasma.
      Plasminogen-binding sites (C-terminal lysines) on the surface of a plasmin
      treated fibrin clot were eliminated within 1-3 min by plasma with maximally
      activated pCPB, as studied in a recently described model involving fluorescence
      microscopy. Confocal fluorescence microscopy showed that in the absence of TM
      plasminogen strongly accumulated on fibrin fibers during t-PA-induced lysis of a
      plasma clot. In the presence of TM (and a concomitant pro-pCPB activation), lysis
      was slow and was not accompanied by accumulation of plasminogen on the fibers. In
      conclusion, generation of active pCPB during clotting of plasma in the presence
      of Ca2+ and TM leads to a retardation of plasma clot lysis in a wide range of t
      PA concentrations, from low to therapeutic, and to a fast elimination of
      plasminogen-binding sites on partially degraded fibrin. This is a likely
      mechanism for the antifibrinolytic effect of active pCPB.

PMID- 9162089
TI  - SHP1 and SHP2 protein-tyrosine phosphatases associate with betac after
      interleukin-3-induced receptor tyrosine phosphorylation. Identification of
      potential binding sites and substrates.
AB  - The cytoplasmic tyrosine phosphatases, SHP1 and SHP2, are implicated in the
      control of cellular proliferation and survival. Here we demonstrate that both
      SHP1 and SHP2 associate with the betac subunit of the human interleukin-3 (IL-3)
      receptor following IL-3 stimulation and that the src homology region 2 (SH2)
      domains of these phosphatases mediate this interaction. Sequential
      immunoprecipitation analyses suggest this interaction is direct. Competition
      studies, using phosphotyrosine-containing peptides based on sequences surrounding
      key tyrosine residues within betac, suggest that phosphorylation of tyrosine 612
      is the key event mediating the association of betac with SHP1 and SHP2. However,
      inhibition of SHP2 binding to betac, did not prevent tyrosine phosphorylation of
      SHP2. Interestingly, this same phosphopeptide served as a substrate for the
      tyrosine phosphatase activity of both SHP1 and SHP2. Binding of these protein
      tyrosine phosphatases to the IL-3 receptor may regulate IL-3 signal transduction
      pathways, both through their catalytic activity and through the recruitment of
      other molecules to the receptor complex.

PMID- 9162091
TI  - Involvement of phosphatidylinositol 3-kinase in NFAT activation in T cells.
AB  - Phosphatidylinositol 3-kinase (PI3-K) has been implicated in the regulation of
      cell proliferation in many cell types. We have previously shown that in T cells
      the PI3-K inhibitor, wortmannin, interferes with activation of the mitogen
      activated kinase, Erk2, after T cell receptor (TcR) stimulation. To further
      explore the involvement of PI3-K in T cell activation, we created a set of
      potentially dominant negative PI3-K constructs comprising individual or tandem
      domains of the regulatory p85 subunit and tested their effect on downstream
      signaling events like Erk2 activation and transcription from an NFAT (nuclear
      factor of activated T cells) element taken from the interleukin-2 promoter.
      Following TcR stimulation, activation of Erk2 was only inhibited by a previously
      described truncated form of p85 that cannot bind the catalytic subunit, but not
      by other constructs of p85. In contrast, several mutant p85 alleles had dramatic
      effects on NFAT activation. Most interestingly, the N-terminal SH2 domain had an
      inhibitory effect, whereas a mutant p85 containing only the two SH2 domains
      enhanced basal NFAT activity in a Ras-dependent manner. Ionomycin induced
      synergistic activation of NFAT in cells expressing p85 mutants that contained the
      C-terminal SH2 domain. Analysis of phosphotyrosine-containing proteins bound to
      truncated p85 constructs revealed cooperative binding of the two SH2 domains but
      no apparent differences between the N- and C-terminal SH2 domains. Wortmannin did
      not interfere with NFAT activation, although it inhibited PI3-K and Erk2
      activation in the same experiment. These results suggest that PI3-K is involved
      in NFAT activation through a complex adaptor function of its regulatory subunit
      and that its lipid kinase activity is dispensable for this effect.

PMID- 9162092
TI  - Characterization of the mitogen-activated protein kinase kinase 4 (MKK4)/c-Jun
      NH2-terminal kinase 1 and MKK3/p38 pathways regulated by MEK kinases 2 and 3. MEK
      kinase 3 activates MKK3 but does not cause activation of p38 kinase in vivo.
AB  - We previously reported the isolation of cDNAs encoding two mammalian mitogen
      activated protein kinase (MAPK)/extracellular-regulated kinase (ERK) kinase
      kinases, designated MEKK2 and MEKK3 (Blank, J.L., Gerwins, P., Elliott, E.M.,
      Sather, S. and Johnson, G.L. (1996) J. Biol. Chem. 271, 5361-5368). In the
      present study, cotransfection experiments were used to examine the regulation by
      MEKK2 and MEKK3 of the dual specificity MAP kinase kinases, MKK3 and MKK4. MKK3
      specifically phosphorylates and activates p38, whereas MKK4 phosphorylates and
      activates both p38 and JNK. Coexpression of MEKK2 or MEKK3 with MKK4 in COS-7
      cells resulted in activation of MKK4, as assessed by enhanced autophosphorylation
      and by its ability to phosphorylate and activate recombinant JNK1 or p38 in
      vitro. MKK3 autophosphorylation and activation of p38 was also observed following
      coexpression of MKK3 with MEKK3, but not with MEKK2. Consistent with these
      observations, immunoprecipitated MEKK2 directly activated recombinant MKK4 in
      vitro but failed to activate MKK3. The sites of activating phosphorylation in
      MKK3 and MKK4 were identified within kinase subdomains VII and VIII. Replacement
      of Ser189 or Thr193 in MKK3 with Ala abolished autophosphorylation and activation
      of MKK3 by MEKK3. Analogous mutations in MKK4 indicated that Ser221 and, to a
      lesser extent, Thr225 were necessary for MKK4 activation by MEKK2 and MEKK3.
      These data indicate that MKK3 is preferentially activated by MEKK3, whereas MKK4
      is activated both by MEKK2 and MEKK3. Consistent with these observations, MEKK2
      and MEKK3 also activated JNK1 in vivo. However, MEKK3 failed to activate p38 when
      coexpressed in either the absence or presence of MKK3, indicating that MEKK3 is
      not coupled to p38 activation in vivo. These observations suggest that regulation
      of p38 and JNK1 pathways by MEKK3 may involve distinct mechanisms to prevent p38
      activation but to allow JNK1 activation.

PMID- 9162093
TI  - Evolution of the proteasome components.
AB  - A phylogenetic analysis of proteasome subunits revealed two major families (alpha
      and beta) which originated by an ancient gene duplication prior to the divergence
      of archaebacteria and eukaryotes. Numerous gene duplications have subsequently
      occurred in eukaryotes; at least nine of these duplications were shown to have
      occurred prior to the divergence of animals and fungi. In mammals, two genes
      encoding proteasome subunits (LMP2 and LMP7) are located in the major
      histocompatibility complex (MHC) region and play a specific role in generation of
      peptides for presentation by class I MHC molecules. Phylogenetic analysis of LMP7
      and related sequences from mammals and lower vertebrates indicated that this
      locus arose by gene duplication prior to the divergence of jawed and jawless
      vertebrates; the time of this duplication was estimated to have been about 600
      million years ago. The evolutionary history of the proteasome subunits provides
      support for a model of the evolution of new gene function postulating that, after
      gene duplication, the proteins encoded by daughter loci can adapt to specialized
      functions previously performed by the product of a single generalized ancestral
      locus.

PMID- 9162094
TI  - Sequence and expression of mouse proteasome activator PA28 and the related
      autoantigen Ki.
AB  - Using reverse transcription polymerase chain reaction, we cloned and sequenced
      full-length mouse cDNAs for the two homologous subunits of the proteasome
      activator PA28 (PA28alpha and PA28beta), as well as for the related protein Ki.
      These proteins are highly conserved among species. Northern blot analysis of
      PA28a, PA28b, and Ki mRNA demonstrated broad tissue distribution. Although single
      transcripts were detected for PA28a and PA28b, two different sized transcripts
      were detected for mouse Ki, suggesting either alternative splicing or alternate
      polyadenylation sites. The levels of these transcripts increased in response to
      interferon-gamma (IFN-gamma) treatment in mouse H6 hepatoma cells, although PA28a
      and PA28b were induced to a greater extent than Ki, and the effect of IFN-gamma
      stimulation on Ki expression was transient. Southern blot analysis suggests that
      both PA28a and PA28b are multiple-copy genes, while Ki is a single-copy gene.

PMID- 9162095
TI  - Cloning of a new human gene with short consensus repeats using the EST database.
AB  - The complement system, which provides many of the effector functions of humoral
      immunity and inflammation, is tightly regulated by various complement regulatory
      proteins. The most common structural feature of these proteins is a motif called
      short consensus repeat (SCR). In order to identify a new human complement
      regulatory protein, we performed a similarity search using SCR on the expressed
      sequence tag (EST) database and found a partial sequence of a new human gene.
      Using a probe containing this partial sequence, we obtained a full-length cDNA of
      this gene from a human umbilical vein endothelial cell (HUVEC) library. The
      sequencing reaction demonstrated an open reading frame of 1383 nucleotides coding
      for a 461 amino acid polypeptide with a deduced relative molecular mass of 51
      000. Structural analysis showed that the protein has three SCRs with one
      transmembrane domain. A characteristic feature of these SCR was that they have
      six conserved cysteines per repeat instead of the usual four. Therefore, we named
      this cDNA THECY (three hexa-cysteine motifs). A six cysteine motif is a
      characteristic feature of selectins. We used northern blot analysis to show that
      a 2.0 kilobase (kb) transcript was ubiquitously present in most organs studied,
      and the mRNA was most abundant in the heart. In conclusion, we discovered a
      member of a new class of membrane-bound SCR-containing molecules using the EST
      database. Utilization of the EST database may be useful in the search for other
      new immunological proteins. The function of this gene remains to be elucidated.

PMID- 9162096
TI  - Diversity associated with the second expressed HLA-DRB locus in the human
      population.
AB  - Although diversity within the HLA-DRB region is predominantly focused in the DRB1
      gene, the second expressed DRB loci, DRB3, DRB4, and DRB5, also exhibit
      variation. Within DRB1(*)15 or DRB1(*)16 haplotypes, four new variants were
      identified: 1) two new DRB5 alleles, DRB5*0104 and DRB5*0204, 2) a haplotype
      carrying a DRB1(*)15 or *16 allele without the usual accompanying DRB5 allele,
      and 3) a haplotype carrying a DRB5(*)0101 allele without a DRB1(*)15 or *16
      allele. The evolutionary origins of these haplotypes were postulated based on
      their associations with the DRB6 pseudogene. Within HLA haplotypes which carry
      DRB3, a new DRB3(*)0205 allele and one unusual DRB3 association were identified.
      Finally, two new null DRB4 alleles are described: DRB4(*)0201N, which exhibits a
      deletion in the second exon, and a second allele, DRB4(*)null, which lacks the
      second exon completely. Gene conversion-like events and variation in the number
      of functional genes through reciprocal recombination and inactivation contribute
      to the diversity observed in the second expressed HLA-DRB loci.

PMID- 9162097
TI  - Genomic organization, chromosomal mapping, and analysis of the 5' promoter region
      of the human MAdCAM-1 gene.
AB  - MAdCAM-1, the endothelial addressin cell adhesion molecule-1, interacts
      preferentially with the leukocyte beta7 integrin LPAM-1 (alpha4beta7), but also
      with L-selectin, and with VLA-4 (alpha4beta1) on myeloid cells, and serves to
      direct leukocytes into mucosal and inflamed tissues. Overlapping cosmid and phage
      lambda genomic clones were isolated, revealing that the human MAdCAM-1 gene
      contains five exons where the signal peptide, two Ig domains, and mucin domain
      are each encoded by separate exons. The transmembrane domain, cytoplasmic domain,
      and 3' untranslated region are encoded together on exon 5. The mucin domain
      contains eight repeats in total that are subject to alternative splicing. Despite
      the absence of a human counterpart of the third IgA-homologous domain and lack of
      sequence conservation of the mucin domain, the genomic organizations of the human
      and mouse MAdCAM-1 genes are similar. An alternatively spliced MAdCAM-1 variant
      was identified that lacks exon 4 encoding the mucin domain, and may mediate
      leukocyte adhesion to LPAM-1 without adhesion to the alternate receptor, L
      selectin. The MAdCAM-1 gene was located at p13.3 on chromosome 19, in close
      proximity to the ICAM-1 and ICAM-3 genes (p13.2-p13.3). PMA-inducible promotor
      activity was contained in a 700 base pair 5' flanking fragment conserved with the
      mouse MAdCAM-1 gene including tandem NF-kB sites, and an Sp1 site; and in
      addition multiple potential AP2, Adh1 (ETF), PEA3, and Sp1 sites. In summary, the
      data establish that the previously reported human MAdCAM-1 cDNA does indeed
      encode the human homologue of mouse MAdCAM-1, despite gross dissimilarities in
      the MAdCAM-1 C-terminal structures.

PMID- 9162098
TI  - Mapping of the human IL10 gene and further characterization of the 5' flanking
      sequence.
AB  - Interleukin-10 (IL-10) is an important regulatory cytokine whose involvement
      extends into diverse areas of the human immune system. Recent characterization of
      the promoter and 5' flanking regions has demonstrated the presence of positive
      and negative regulatory segments in the promoter. In addition, the
      characterization of two dinucleotide repeat elements immediately upstream of the
      gene has shown that there is considerable polymorphism directly associated with
      the human IL10 gene. In the present report, we describe the mapping of the human
      IL10 gene to a discrete area of chromosome 1, the definition of a potential
      cytokine-responsive segment 3 - 4 kilobases upstream of the transcription
      initiation site, and the identification of two new point mutations in the
      immediate promoter region with their distribution in a panel of 75 unrelated
      healthy individuals. These data should further the understanding of how the IL10
      gene is controlled in humans and how its function may vary between individuals.

PMID- 9162099
TI  - Mapping of mhc class I and class II regions to different linkage groups in the
      zebrafish, Danio rerio.
AB  - The mammalian major histocompatibility complex (Mhc) consists of three closely
      linked regions, I, II, and III, occupying a single chromosomal segment. The class
      I loci in region I and the class II loci in region II are related in their
      structure, function, and evolution. Region III, which is intercalated between
      regions I and II, contains loci unrelated to the class I and II loci, and to one
      another. There are indications that a similar Mhc organization exists in birds
      and amphibians. Here, we demonstrate that in the zebrafish (Danio rerio), a
      representative of the teleost fishes, the class II loci are divided between two
      linkage groups which are distinct from the linkage group containing the class I
      loci. The beta2-microglobulin-encoding gene is loosely linked to one of the class
      II loci. The gene coding for complement factor B, which is one of the region III
      genes in mammals, is linked neither to the class I nor to the class II loci in
      the zebrafish. These results, combined with preliminary data suggesting that the
      class I and class II regions in another order of teleost fish are also in
      different linkage groups, indicate that close linkage of the two regions is not
      necessary either for regulation of expression or for co-evolution of the class I
      and class II loci. They also raise the question of whether linkage of the class I
      and class II loci in tetrapods is a primitive or derived character.

PMID- 9162100
TI  - Large-scale comparative mapping of the MHC class I region of predominant
      haplotypes in Japanese.
AB  - In order to further our understanding of major histocompatibility complex (MHC)
      class I gene organization, we began a comparative analysis of the large scale
      organization of the class I region in diverse haplotypes. For these studies, the
      MHC in healthy Japanese donors who have the predominant MHC haplotypes and/or HLA
      A or -B alleles was examined by pulsed field gel electrophoresis and Southern
      analysis using probes spanning the class I region. Hybridization with probes from
      the HLA-A to HLA-G region revealed that individuals expressing HLA-A30, -A31, or 
      A33 have an approximately 70 kilobase (kb) insertion near the HLA-A gene as
      compared with haplotypes containing the HLA-A11 or -A26 allele. Conversely, HLA
      A24-containing haplotypes appear to have an approximately 50 kb deletion from the
      same region. Further, it appears that chromosomes carrying closely related
      alleles are similar to each other in this region, consistent with their presumed
      evolutionary relationship. While little is known about the gene content between
      the HLA-A and HLA-G region, it will be interesting to examine the prospect that
      functional genes do in fact reside within the inserted or deleted portions,
      thereby raising the possibility that distinct functional differences are
      conferred by different haplotypes. Overall, the results reported here should
      contribute to furthering our understanding of the association between diseases
      and HLA as well as provide new insights into the evolution of the MHC.

PMID- 9162101
TI  - Modulation of mRNA levels in the presence of thymocytes and genome mapping for a
      set of genes expressed in mouse thymic epithelial cells.
AB  - Modulation of gene expression in mouse thymic epithelium upon culture in the
      presence of thymocytes (coculture) was studied by comparison of hybridization
      signatures on a set of nearly 5000 mouse thymus cDNA clones. Forty-nine
      differentially expressed clones (usually down-regulated in coculture) were
      characterized by tag sequencing. Many of them corresponded to entities that had
      not been described previously in the mouse, and were further characterized by
      genome mapping. This set of genes appears to be involved in growth regulation and
      differentiation within the thymus.

PMID- 9162102
TI  - 5' regulatory nucleotide sequence of an HLA-A*0101null allele.
AB  - We have previously demonstrated an HLA-A*0101null allele segregating in a family
      with the HLA-B8, -Cw7, -DR3, -DR52, -DQ2 haplotype. In the present study the
      regulatory elements with known transcription enhancement activity of the silenced
      HLA-A*0101 allele were analyzed. In the enhancer B element, a T was substituted
      for a C at position - 106, whereas no other alterations were found in the
      adjacent 5' section of the HLA-A*0101null allele. This substitution was not seen
      in the enhancer B elements of the corresponding genes involved in normal HLA
      A*0101 membrane expression. Comparison of enhancer B element sequences of
      classical functional major histocompatibility complex (MHC) class I alleles
      demonstrated a high degree of conservation. In contrast, many MHC class I
      pseudogenes showed mutation in their enhancer B boxes. These results may indicate
      that the single mutation detected in the enhancer B element plays a pivotal role
      in the abolishment of membrane expression of the HLA-A*0101null allele.

PMID- 9162104
TI  - The human natural killer gene complex (NKC) is located on chromosome 12p13.1
      p13.2.

PMID- 9162103
TI  - Promoter region of the human eosinophil cationic protein gene.

PMID- 9162105
TI  - The Mtv29 gene encoding endogenous lymphoma superantigen in SJL mice, mapped to
      proximal chromosome 6.

PMID- 9162106
TI  - The Igh-1 sequence of the non-obese diabetic (NOD) mouse assigns it to the IgG2c
      isotype.

PMID- 9162107
TI  - From Daphnia to yeast - two decades of mitochondrial research in Munich.

PMID- 9162108
TI  - Translational activator proteins required for cytochrome b synthesis in
      Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae translation of apocytochrome b, the only
      mitochondrially encoded subunit of ubiquinol-cytochrome c oxidoreductase,
      requires the products of at least three nuclear genes, CBP6, CBS1 and CBS2. In
      this article I review available data on CBS1p and CBS2p from the initial
      detection of the genes up to the current investigations on interacting components
      and the proteins' topology.

PMID- 9162109
TI  - The fungal mitochondrial genome project: evolution of fungal mitochondrial
      genomes and their gene expression.
AB  - The goal of the fungal mitochondrial genome project (FMGP) is to sequence
      complete mitochondrial genomes for a representative sample of the major fungal
      lineages; to analyze the genome structure, gene content, and conserved sequence
      elements of these sequences; and to study the evolution of gene expression in
      fungal mitochondria. By using our new sequence data for evolutionary studies, we
      were able to construct phylogenetic trees that provide further solid evidence
      that animals and fungi share a common ancestor to the exclusion of chlorophytes
      and protists. With a database comprising multiple mitochondrial gene sequences,
      the level of support for our mitochondrial phylogenies is unprecedented, in
      comparison to trees inferred with nuclear ribosomal RNA sequences. We also found
      several new molecular features in the mitochondrial genomes of lower fungi,
      including: (1) tRNA editing, which is the same type as that found in the
      mitochondria of the amoeboid protozoan Acanthamoeba castellanii; (2) two novel
      types of putative mobile DNA elements, one encoding a site-specific endonuclease
      that confers mobility on the element, and the other constituting a class of
      highly compact, structured elements; and (3) a large number of introns, which
      provide insights into intron origins and evolution. Here, we present an overview
      of these results, and discuss examples of the diversity of structures found in
      the fungal mitochondrial genome.

PMID- 9162110
TI  - The yeast ORF YDL202w codes for the mitochondrial ribosomal protein YmL11.
AB  - The Saccharomyces cerevisiae open reading frame YDL202w has been characterised in
      the course of the EUROFAN yeast genome analysis program. Disruption of YDL202w
      causes a respiratory deficient phenotype accompanied by a loss of mitochondrial
      DNA. This phenotype is usually found in mutants defective in mitochondrial
      replication or gene expression. YDL202w has the potential to encode a soluble
      protein of 249 amino acids. It shows significant similarities to the ribosomal
      protein L10 from various bacteria and to a previously determined amino-terminal
      peptide sequence of the yeast mitochondrial ribosomal protein L11. The predicted
      amino-acid sequence of YDL202w starts with a stretch which has neither any
      correspondence in the bacterial sequences nor in the protein isolated from
      mitochondrial ribosomes. Furthermore, this stretch matches the requirements for a
      signal sequence for mitochondrial protein import. A mitochondrial location of the
      YDL202w gene product was proven by use of a carboxy terminally HA-tagged version.
      These findings clearly indicate that YDL202w encodes this mitochondrial ribosomal
      protein (YmL11).

PMID- 9162111
TI  - A mutation in cytochrome oxidase subunit 2 restores respiration of the mutant pet
      ts1402.
AB  - The yeast PET1402/OXA1 gene encoding a 44.8-kDa protein is required for
      mitochondrial biogenesis. Substitution of Leu240 to serine in the protein results
      in an accumulation of the precursor form of the mitochondrially encoded subunit 2
      of cytochrome oxidase (Cox2) and temperature-sensitive respiration. This
      temperature sensitivity can be suppressed by a mutation in the cox2 gene changing
      Ala189 of the Cox2 protein to proline. In the cox2-ts1402 double mutant
      respiration is restored without removal of the Cox2 pre-sequence. The suppression
      suggests an interaction of the Pet1402 protein with the cytochrome oxidase
      complex. Antibodies raised against the predicted C-terminus and the tagged N
      terminus of the Pet1402 protein reacted with a 37-kDa polypeptide. This protein,
      present in the mitochondrial fraction, is localized within the inner membrane.
      The difference in size can be explained by the removal of the predicted
      mitochondrial-targeting sequence from the Pet1402 protein. The mitochondrial
      localization of the protein points to a direct interaction with the cytochrome
      oxidase complex.

PMID- 9162112
TI  - Starvation for a specific amino acid induces high frequencies of rho- mutants in
      Saccharomyces cerevisiae.
AB  - Auxotrophic yeast cells were starved on solid media for their respective
      essential amino acid in the course of "adaptive mutation" experiments. Thereby,
      high proportions of mitochondrially respiratory deficient (rho-) mutants
      accumulated among the cells stressed on selective plates. Using a strain with a
      plus-four frameshift mutation in a chromosomal gene involved in lysine
      biosynthesis, we observed that many of the revertant colonies which arose late
      under the selective pressure were composed of mixtures of rho+ and rho- cells,
      indicating that they originated from founder cells containing intact as well as
      defective mitochondrial genomes. We show that in spite of the slower growth of
      rho- cells the late-appearing colonies cannot be interpreted as descending from
      rho- revertants present before selective plating.

PMID- 9162113
TI  - The apocytochrome-b gene in Chlorogonium elongatum (Chlamydomonadaceae): an
      intronic GIY-YIG ORF in green algal mitochondria.
AB  - The mitochondrial cob gene from the green alga Chlorogonium elongatum
      (Chlamydomonadaceae) is interrupted by two group-I introns each containing an
      open reading frame in-phase with the upstream exon. One of these ORFs belongs to
      the LAGLI-DADG family, the other to the GIY-YIG family. The latter has not yet
      been identified in any mitochondrial genome except those from fungi. The
      Chlorogonium ORFs are similar to ORFs encoded by fungal introns that are located
      at an identical position within the gene, and to the ORF encoded by the mobile
      intron in the Chlamydomonas smithii cob gene.

PMID- 9162114
TI  - The highly rearranged chloroplast genome of Trachelium caeruleum (Campanulaceae):
      multiple inversions, inverted repeat expansion and contraction, transposition,
      insertions/deletions, and several repeat families.
AB  - Comprehensive gene mapping reveals that the chloroplast genome of Trachelium
      caeruleum is highly rearranged relative to those of other land plants.
      Evolutionary scenarios that consist of seven to ten inversions, one or two
      transpositions, both expansion and contraction of the typically size-conserved
      inverted repeat, a presumed gene loss, deletions within two large open reading
      frames and several insertions, are sufficient to derive the Trachelium
      arrangement from the ancestral angiosperm chloroplast DNA arrangement. Two of the
      rearrangements disrupt transcriptional units that are otherwise conserved among
      land plants. At least five families of small dispersed repeats exist in the
      Trachelium chloroplast genome. Most of the repeats are associated with inversion
      endpoints and may have facilitated inversions through recombination across
      homologous repeats.

PMID- 9162115
TI  - Multiple recruitment of class-I aldolase to chloroplasts and eubacterial origin
      of eukaryotic class-II aldolases revealed by cDNAs from Euglena gracilis.
AB  - The photosynthetic protist Euglena gracilis is one of few organisms known to
      possess both class-I and class-II fructose-1,6-bisphosphate aldolases (FBA). We
      have isolated cDNA clones encoding the precursor of chloroplast class-I FBA and
      cytosolic class-II FBA from Euglena. Chloroplast class-I FBA is encoded as a
      single subunit rather than as a polyprotein, its deduced transit peptide of 139
      amino acids possesses structural motifs neccessary for precursor import across
      Euglena's three outer chloroplast membranes. Evolutionary analyses reveal that
      the class-I FBA of Euglena was recruited to the chloroplast independently from
      the chloroplast class-I FBA of chlorophytes and may derive from the cytosolic
      homologue of the secondary chlorophytic endosymbiont. Two distinct subfamilies of
      class-II FBA genes are shown to exist in eubacteria, which can be traced to an
      ancient gene duplication which occurred in the common ancestor of contemporary
      gram-positive and proteobacterial lineages. Subsequent duplications involving
      eubacterial class-II FBA genes resulted in functional specialization of the
      encoded products for substrates other than fructose-1,6-bisphosphate. Class-II
      FBA genes of Euglena and ascomycetes are shown to be of eubacterial origin,
      having been acquired via endosymbiotic gene transfer, probably from the
      antecedants of mitochondria. The data provide evidence for the chimaeric nature
      of eukaryotic genomes.

PMID- 9162116
TI  - The actin gene of the glaucocystophyte Cyanophora paradoxa: analysis of the
      coding region and introns, and an actin phylogeny of eukaryotes.
AB  - We isolated the actin gene of the glaucocystophyte alga Cyanophora paradoxa and
      analyzed the coding region and its introns. Phylogenetic analyses of the actin
      coding region and the inferred protein sequence in data sets containing 47 other
      actin sequences show Cyanophora to be a member of the eukaryotic crown-group
      radiation in agreement with ribosomal DNA sequence analyses. Four of the five
      Cyanophora actin introns are relatively short (55-59 nt) and occupy novel
      positions in a catalogue of actin introns containing 56 distinct sites. The fifth
      intron has a length of 171 nt and occurs also in actin genes from green algae and
      the crustacean Artemia.

PMID- 9162117
TI  - Cloning and characterisation of glutamine synthetase from Colletotrichum
      gloeosporioides and demonstration of elevated expression during pathogenesis on
      Stylosanthes guianensis.
AB  - Experiments were designed to clone and identify genes of the fungal phytopathogen
      Colletotrichum gloeosporioides expressed at high levels during growth on the
      compatible host Stylosanthes guianensis when compared with expression in axenic
      culture. A cDNA clone (pCgGS) that hybridised preferentially to a cDNA probe
      prepared from infected leaves was isolated by the differential screening of a
      cDNA library from a nitrogen-starved axenic culture of C. gloeosporioides. The
      DNA sequence of pCgGS is highly homologous to genes for glutamine synthetase (GS)
      in other organisms. pCgGS contained all of the conserved regions assigned as
      catalytic domains in GS enzymes. Comparison with genomic sequences indicated that
      in C. gloeosporioides the GS gene is present as a single copy with three introns.
      To our knowledge this is the first report of the cloning of a GS from a
      filamentous fungus. A second clone (pCgRL1) was also isolated and represented a
      partial cDNA of the 25s rRNA of C. gloeosporioides. Because pCgRL1 did not
      hybridise to plant rRNA under high-stringency hybridisation conditions, it was
      used as a reference to quantify the expression of fungal GS mRNA during
      pathogenesis in S. guianensis compared to fungal growth in axenic culture. The
      results indicated that elevated expression of GS occurred during pathogenesis of
      C. gloeosporioides on S. guianensis, particularly at early stages of infection
      where expression was about six-times higher than during growth in rich culture
      media. This work also demonstrates that fungal-specific 25s rRNA fragments, such
      as pCgRL1, have considerable utility as a reference for quantifying pathogen gene
      expression in infected plants.

PMID- 9162119
TI  - Endoscopic sinus surgery. A review.
AB  - Endoscopic sinus surgery has progressed from a limited surgical intervention for
      chronic sinus disease to a viable approach for diffuse sinonasal polyposis,
      benign tumors, skull base defects, and orbital lesions. Some aspects of
      endoscopic diagnosis and treatment, however, remain controversial and are poorly
      understood. Controversies in endoscopic sinus surgery are reviewed and the
      primary critical issues with regard to the more recently developed
      instrumentation and the newer extended approaches are presented.

PMID- 9162120
TI  - Antimicrobial therapy for sinusitis.
AB  - Rational antibiotic therapy for sinusitis is a difficult goal, made difficult by
      few satisfactory comparative trials with sufficient clinical power, the large
      numbers of therapeutic options, prescribing pressures from the pharmaceutical
      industry, and rapid changes in bacterial resistance patterns. Controversies exist
      about the relative need of antibiotics for uncomplicated disease, duration of
      therapy, and relative efficacy of various agents. Nonetheless, limited data
      support the notion of superior efficacy of more potent antimicrobials, and an
      analysis of in vitro activity versus tissue concentrations of the various
      antibiotics can predict efficacy of eradication of causative bacteria. Multidrug
      resistant pneumococci render any algorithm for empiric antibiotic use problematic
      and prone to fail.

PMID- 9162121
TI  - The small-hole technique in endoscopic sinus surgery.
AB  - It may be that the uncinate process, the posteromedial wall of the agger nasi,
      and the medial wall of the ethmoid bulla are the critical anatomic components in
      recalcitrant sinus disease. The basal lamella may be a fourth component. It may
      be that addressing these "transition spaces" is all that is required in cases of
      sinusitis requiring surgical treatment. Quantitative studies and outcome studies
      are necessary. Minimally invasive, "small hole" sinus surgery may offer the
      prospect of reversibility of disease in the paranasal sinuses with limited
      surgical intervention.

PMID- 9162122
TI  - Current concepts in the surgical management of chronic frontal sinusitis.
AB  - The surgical management of chronic frontal sinusitis has lagged behind that of
      other sinuses because of a relative infrequency of the disease, the difficulty in
      diagnosing it, the anatomical complexity of the area involved, an inadequate
      understanding of the airflow and mucus drainage pathways, the complexity and lack
      of success of surgical procedures, and the need for advanced equipment. A review
      of the anatomy, embryology, and physiology of the nasofrontal region is given
      followed by a summary of the signs, symptoms, and radiologic findings of chronic
      frontal disease because often the most difficult decision is knowing when to
      intervene surgically. Finally, there is a discussion of current techniques and
      recent advances using powered instrumentation in the nasofrontal area.

PMID- 9162123
TI  - Current status and new developments in techniques for imaging the nose and
      sinuses.
AB  - CT scans and MR images have matured as the mainstays of imaging of the nasal
      cavity and paranasal sinuses. This review covers the current status of imaging in
      regards to benign and malignant sinus disease. A review of current imaging
      methodology and a look at emerging technologies, which hold promise for
      evaluating the proximal airways, is provided.

PMID- 9162124
TI  - Computer-assisted endoscopic sinus surgery. An international review.
AB  - Computer-assisted technology provides the surgeon with accurate guidance during
      endonasal sinus procedures. This article reviews early experiences in Europe and
      the United States. Various types of probe technology and their accuracy and ease
      of use are examined.

PMID- 9162125
TI  - An anatomic approach to local anesthesia for surgery of the nose and paranasal
      sinuses.
AB  - This is a review of the innervation of the midface and nose as a guide to
      anesthesia in this region. Through an understanding of the embryologic
      development, better predictions of nerve coverage are possible. The variables
      encountered during surgery can be appreciated, and in a practical sense this
      leads to anesthetic approaches that allow comfortable and controlled surgery in
      this area.

PMID- 9162126
TI  - Technical considerations in powered instrumentation.
AB  - This article reviews some of the technical engineering aspects of the soft-tissue
      shavers and bone-cutting drills. An improved understanding of these principles
      may allow the practicing surgeon to optimize the desired aggressiveness and
      precision of the instrument in his or her hands. Powered instrumentation has
      found extended uses beyond sinus disease, such as submental lipectomy (soft
      tissue shaver) and modifying the bony nasal dorsum (bone cutting bur). Changes in
      drill design to address these and other surgical situations are discussed.

PMID- 9162127
TI  - Soft-tissue shavers in functional endoscopic sinus surgery (standard technique).
AB  - The use of powered soft-tissue shavers in standard functional endoscopic sinus
      surgery offers significant advantages over the use of standard instrumentation.
      Increased safety, improved results, decreased blood loss, and potential cost
      savings are significant advances offered by the use of this instrumentation.

PMID- 9162128
TI  - Soft-tissue shavers in pediatric sinus surgery.
AB  - Powered instrumentation represents the newest advance in endoscopic sinus
      surgery. These instruments can be used in a variety of areas of the nose and
      paranasal sinuses. They can be particularly helpful for sinus surgery in
      children, who have smaller anatomic spaces and closer proximity of vital
      structures. The shaving action combined with continuous real-time suction of the
      soft-tissue shavers can provide the technical advantage to allow greater
      precision and ease in performing pediatric endoscopic sinus surgery.

PMID- 9162129
TI  - Lasers in endonasal surgery.
AB  - The laser has played a valuable primary and adjunctive role in the management of
      nasal and sinus disorders. When using the laser there must be appropriate
      knowledge about safety, instrumentation, and types of pathologic conditions in
      which the laser is effective. The laser is effective for turbinate dysfunction of
      various causes. Its coagulating, cutting, and vaporization ability make it useful
      in managing intranasal vascular disorders such as hereditary hemorrhagic
      telangiectasia and hemangioma. There is some promise in using the laser for nasal
      polyposis with eosinophilia.

PMID- 9162130
TI  - Advanced drill technology in treatment of congenital choanal atresia.
AB  - Congenital choanal atresia is a challenging clinical problem requiring prompt
      diagnosis and intervention. The method of repair is controversial, with no
      technique having gained universal acceptance. Proponents of the transnasal repair
      must acknowledge the variability of results, especially with thick bony plates,
      and the technical difficulties associated with this method. Advocates of the
      transpalatal route must recognize the associated morbidity of this technique in
      the newborn. The adaptation of the endoscopic technique and the development of
      new powered instrumentation have significantly improved the transnasal technique
      so that safe controlled repair may now be accomplished in the newborn.

PMID- 9162131
TI  - Powered instrumentation in orbital and optic nerve decompression.
AB  - Powered instrumentation in orbital and optic nerve decompression is a helpful
      adjunct to performing safe, functional, and complete surgery. The microdebrider
      and the drill are the powered instruments most often used. Combined with
      endoscopic visualization, these tools provide appropriate drainage and
      decompression whether for orbital abscesses, Grave's ophthalmopathy, or optic
      nerve injury.

PMID- 9162132
TI  - Advances in postoperative care following functional endoscopic sinus surgery.
AB  - The ultimate success of functional endoscopic sinus surgery often is determined
      during the period of postoperative care. Final surgical results are greatly
      influenced by preoperative surgical planning and intraoperative decision-making.
      One goal of postoperative care includes the prevention of scar formation, such as
      middle turbinate collapse. Specific techniques include mucosal preservation,
      middle meatal spacer corticosteroids and culture-directed antibiotics.

PMID- 9162133
TI  - Folding & Design: introduction to a new journal.

PMID- 9162134
TI  - Testing homology modeling on mutant proteins: predicting structural and
      thermodynamic effects in the Ala98-->Val mutants of T4 lysozyme.
AB  - Backgound. Current approaches to homology modeling predict how amino acid
      substitutions will alter a protein's structure, primarily by modeling sidechain
      conformations upon essentially immobile backbone frameworks. However, recent
      crystal structures of T4 lysozyme mutants reveal significant shifts of the
      mainchain and other potentially serious problems for sidechain rotamer-based
      modeling. This paper evaluates the accuracy of structural and thermodynamic
      predictions from two common sidechain modeling approaches to measure errors
      caused by the fixed-backbone approximation. Results. Tested on a series of T4
      lysozyme mutants, this sidechain rotamer library approach did not handle
      mainchain shifts well, correctly predicting the sidechain conformations of only
      two of six mutants. By contrast, allowing sidechains to move more flexibly
      appeared to compensate for the rigidity of the mainchain and gave reasonably
      accurate coordinate predictions (rms errors of 0.5-1.0 &angst; for each mutated
      sidechain), better on average than 90% of possible conformations. The calculated
      packing energies correlated well with experimental stabilities (r2=0.81) and
      correctly captured the cooperative interactions of several neighboring mutations.
      Conclusion. Mutant modeling can be relatively accurate despite the fixed-backbone
      approximation. Mainchain shifts (0.2-0.5 &angst;) cause increased sidechain
      coordinate errors of 0.1-0.8 &angst;, torsional errors of 10-30&deg;, and
      exaggerated strain energy for overpacked mutants, compared with the same
      calculations performed with the correct mutant backbones.

PMID- 9162135
TI  - Scrapie prions: a three-dimensional model of an infectious fragment.
AB  - Backgound. A conformational change seems to represent the major difference
      between the scrapie prion protein (PrPSc) and its normal cellular isoform (PrPC).
      We recently proposed a set of four helix bundle models for the three-dimensional
      structure of PrPC that are consistent with a variety of spectroscopic and genetic
      data. Results. We report a plausible model for the three-dimensional structure of
      a biologically important fragment of PrPSc. The model of residues 108-218 was
      constructed by an approach that combines computational techniques and
      experimental data. The proposed structures of this fragment of PrPSc display a
      four-stranded beta-sheet covered on one face by two alpha-helices. Residues
      implicated in the prion species barrier are found to cluster on the solvent
      accessible surface of the beta-sheet of one of the models. This interface could
      provide a structural template that would assist the conversion of PrPC to PrPSc
      and hence direct prion propagation. Conclusion. Molecular models of the PrP
      isoforms should prove very useful in developing structural hypotheses about the
      process by which PrPC is transformed into PrPSc, the mechanisms by which PrP gene
      mutations give rise to the inherited human prion diseases, and the species
      barrier that seems to protect humans from animal prions. It seems likely that
      PrPC represents a kinetically trapped intermediate in PrP folding.

PMID- 9162136
TI  - Non-detergent sulphobetaines: a new class of molecules that facilitate in vitro
      protein renaturation.
AB  - Backgound. Attempts to renature proteins often yield aggregates rather than
      native protein. To minimize aggregation, low protein concentrations and/or
      solubilizing agents are used. Here, we test new solubilizing molecules, non
      detergent sulphobetaines, to improve the renaturation of two very different
      enzymes, hen egg white lysozyme and bacterial beta-D-galactosidase. Results. The
      renaturation was conducted in the presence of five different sulphobetaines and
      the yield of active enzyme was measured. The five sulphobetaines improved the
      yield of native lysozyme up to 12-fold. Some sulphobetaines improved the yield of
      galactosidase up to 80-fold, but one reduced it 100-fold. Conclusion. Non
      detergent sulphobetaines strongly affect the balance between aggregation and
      folding. Their effect depends on their structure and on their interactions with
      folding intermediates. These results should serve as a basis for designing more
      efficient sulphobetaines; for designing improved renaturation protocols using
      existing sulphobetaines; and for characterizing folding intermediates that
      interact with sulphobetaines.

PMID- 9162137
TI  - Stabilization of proteins by rational design of alpha-helix stability using
      helix/coil transition theory.
AB  - Backgound. Increasing protein stability is a major goal of protein engineering
      because of its potential industrial and pharmacological applications. Several
      different rule-of-thumb strategies have been employed for such a purpose, but a
      general rational method is still lacking. Recently, there has been significant
      progress in our understanding of the interactions responsible for helix stability
      in monomeric peptides and this information has been included in algorithms based
      on the helix/coil transition theory. We set out to investigate whether it is
      possible to use these algorithms to rationally increase protein stability.
      Results. Using a helix/coil transition algorithm, AGADIRms, we have designed
      mutations affecting solvent-exposed residues which, as predicted, significantly
      increase the helical stability in aqueous solution of peptides corresponding to
      the two alpha-helices of the activation domain of procarboxipeptidase A.
      Introduction of the same mutations in the protein results in proteins more
      resistant to urea or temperature denaturation, and there is a qualitative
      agreement between the expected and observed increases in stability. Conclusion.
      In this work we demonstrate that by using a helix/coil algorithm to design helix
      stabilizing mutations on the solvent-exposed face of helices, it is possible to
      rationally increase the stability of proteins.

PMID- 9162138
TI  - Structure of the transition state for folding of the 129 aa protein CheY
      resembles that of a smaller protein, CI-2.
AB  - Backgound. Protein engineering analysis has been used as a tool to determine the
      structure of the transition state of two different proteins: CI-2 and barnase. CI
      2 belongs to the group of small, globular proteins with no disulphide bonds that
      fold via a two-state mechanism. Barnase is a larger protein (110 aa) and displays
      a folding intermediate. The structure of the transition state of both proteins is
      quite different. Whereas in CI-2 no region is fully native and it looks like an
      expanded form of the folded state, in barnase several regions are folded and the
      rate-limiting step seems to be the consolidation of the hydrophobic core. On the
      basis of these results, a unified scheme for the transition state of protein
      folding has been presented. We decided to characterize the folding pathway, or
      pathways, present in the alpha/beta parallel family of proteins using one of the
      smallest members, CheY (129 aa), as a model case. Results. The folding pathway of
      CheY contains, as does that of barnase, a kinetic intermediate. The picture
      obtained for CheY from the equilibrium and kinetic analyses of several mutations
      scattered throughout the whole protein is different from that found for barnase.
      On the basis of the experimental results and the structure of CheY, the protein
      can be divided into two subdomains (from beta-strand 1 to beta-strand 3 and from
      beta-strand 3 to the C terminus). Whereas the structure of the first subdomain in
      the transition state resembles that found for the CI-2 protein, the second
      subdomain is compact but unstructured. The packing of the first alpha-helix
      against beta-strands 1 and 2 seems to be the nucleus around which the rest of the
      protein folds. Conclusion. Comparison of the transition state of barnase with
      those of CheY and CI-2 indicates that different proteins have different
      transition states, probably depending on the energetics and the position of the
      rate-limiting step in the folding pathway. CheY appears to fold through a
      nucleation/condensation mechanism as has been found for CI-2. The rate
      determining step in some multi-modular proteins could be the formation of a
      stable domain, with the less stable domains folding after the major rate
      determining step.

PMID- 9162139
TI  - Redesigning the substrate specificity of the hepatitis C virus NS3 protease.
AB  - Backgound. Hepatitis C Virus (HCV) non-structural protein 3 (NS3) encodes a
      trypsin-like serine protease that catalyzes the cleavages at the NS3/NS4A,
      NS4A/NS4B, NS4B/NS5A and NS5A/NS5B junctions in the viral polyprotein and that
      shows a preference for a cysteine as the P1 residue. Results. We describe here a
      partial model of the HCV NS3 protease which allowed us to predict the position of
      the secondary structure elements of the enzyme and of the residues involved in
      its specificity. By replacing these with the corresponding residues of
      Streptomyces griseus protease B, we obtained a protease that, similar to the
      bacterial protein and unlike the wild-type enzyme, is able to cleave a substrate
      containing a phenylalanine in the P1 position. Conclusion. These results confirm
      the reliability of our model and represent one of the few examples of redesign of
      a serine protease substrate specificity directed by molecular modelling.

PMID- 9162140
TI  - Crystallization of a designed peptide from a molten globule ensemble.
AB  - Backgound. The design of amino acid sequences that adopt a desired three
      dimensional fold has been of keen interest over the past decade. However, the
      design of proteins that adopt unique conformations is still a considerable
      problem. Until very recently, all of the designed proteins that have been
      extensively characterized possess the hallmarks of the molten globular state.
      Molten globular intermediates have been observed in both equilibrium and kinetic
      protein folding/stability studies, and understanding the forces that determine
      compact non-native states is critical for a comprehensive understanding of
      proteins. This paper describes the solution and early solid state
      characterization of peptides that form molten globular ensembles. Results.
      Crystals diffracting to 3.5&angst; resolution have been grown of a 16-residue
      peptide (alpha1A) designed to form a tetramer of alpha-helices. In addition, a
      closely related peptide, alpha1, has previously been shown to yield crystals that
      diffract to 1.2&angst; resolution. The solution properties of these two peptides
      were examined to determine whether their well defined crystalline conformations
      were retained in solution. On the basis of an examination of their NMR spectra,
      sedimentation equilibria, thermal unfolding, and ANS binding, it is concluded
      that the peptides form alpha-helical aggregates with properties similar to those
      of the molten globule state. Thus, for these peptides, the process of
      crystallization bears many similarities to models of protein folding. Upon
      dissolution, the peptides rapidly assume compact molten globular states similar
      to the molten globule like intermediates that are formed at short times after
      refolding is initiated. Following a rate-determining nucleation step, the
      peptides crystallize into a single or a small number of conformations in a
      process that mimics the formation of native structure in proteins.

PMID- 9162141
TI  - Unfolded BPTI variants with a single disulfide bond have diminished non-native
      structure distant from the crosslink.
AB  - Backgound. NMR studies of denatured states, both fully unfolded and partially
      folded, give insight into the conformations and interactions favored in initial
      stages of folding, and in early intermediates formed during folding. We have
      characterized non-random structures favored in unfolded, reduced BPTI [1], and in
      partially folded BPTI [2]. Here, we report NMR-detected structure of two analogs
      of unfolded BPTI with one native 14-38 disulfide bond. Results. Analogs Y21A[14
      38]Abu and Y23A[14-38]Abu, obtained by chemical synthesis of [14-38]Abu with Y21
      or Y23 replaced by alanine, are models for unfolded BPTI with 14-38 the only
      disulfide. Compared to unfolded BPTI with all three disulfides broken, the
      unfolded 14-38 BPTI analogs have numerous differences, including loss of non
      native, turn-like conformations for beta2 residues, diminished non-native
      aromatic-aliphatic NOEs, and increased intermediate chemical exchange of residues
      that have native-like conformations in partially folded BPTI. Although the Y21A
      and Y23A analogs have similar CD and NMR properties, specific differences in NOE
      patterns and in exchange broadening are observed. Conclusion. Changes in unfolded
      BPTI associated with formation of the 14-38 disulfide bond are consistent with
      less non-native structure, and more native-like structure, in residues composing
      the stable core of antiparallel beta-sheet in partially folded BPTI. Specific
      differences between Y21A[14-38]Abu and Y23A[14-38]Abu indicate that replacement
      of Y23 results in less ordered structure than replacement of Y21.

PMID- 9162142
TI  - A Continuous Publication System.

PMID- 9162143
TI  - Revisiting the Anfinsen cage.
AB  - In the past five years, ideas about protein folding inside cells have changed as
      a results of experiments with the chaperonin family of molecular chaperones. The
      folding of at least some proteins is no longer regarded as a spontaneous energy
      independent process, but as involving transient interactions with chaperonin
      ATPases that serve to increase the efficiency of correct folding within the
      highly crowded intracellular environment. This review discusses in an historical
      context one model for how the chaperonins function. This model suggests that
      proteins fold inside cells in the same way as they do in pure dilute solution,
      but that they do so inside macromolecular Anfinsen cages that serve as
      sequestration devices to prevent and reverse unproductive interactions.

PMID- 9162144
TI  - On-pathway versus off-pathway folding intermediates.
AB  - Rapidly formed molten globule intermediates accumulate at the start of the
      folding reactions of several small proteins. Opinion is sharply divided as to
      whether they are on-pathway or off-pathway intermediates. I discuss recent
      experiments aimed at resolving this issue. Specific points include whether a
      'rollover' in the plot of folding rate versus denaturant concentration implies
      that a folding intermediate is or is not on-pathway; whether the failure to
      observe folding intermediates for some small proteins implies a different folding
      mechanism or only that the intermediates are less stable; possible interpretation
      of 'fast-track' folding of hen lysozyme; and the significance of recent results
      in the search for unfolding intermediates.

PMID- 9162145
TI  - Adding backbone to protein folding: why proteins are polypeptides.
AB  - It is argued that the chemical nature of the polypeptide backbone is the central
      determinant of the three-dimensional structures of proteins. The requirement that
      buried polar groups form intramolecular hydrogen bonds limits the fold of the
      backbone to the well known units of secondary structure while the amino acid
      sequence chooses among the set of conformations available to the backbone.
      'Sidechain-only' models, based for example on hydrophobicity patterns, fail to
      account for the properties of the backbone and thus will have difficulty
      capturing essential features of a folding pathway. This is evident from the
      incorrect predictions they make for the conformations of the limiting cases of
      all-hydrophobic or all-polar sequences.

PMID- 9162151
TI  - [The PRINS technique. Aplication to the detection of X and Y chromosomes for
      follow-up of bone marrow allografts performed with an opposite sex donor].
AB  - The PRimed IN Situ synthesis is a method for rapid identification of chromosomes
      in metaphase or interphase on cytological preparations and frozen tissue
      sections, using oligonucleotide primers derived from chromosome specific subsets
      of repeated DNA families. PRINS technique is an alternative to fluorescence in
      situ hybridization, as sensitive as FISH but faster and more specific. This
      technique is potentially of great interest for pathologists involved in
      transplantation pathology or cytogenetic interphasic oncology.

PMID- 9162152
TI  - [Amplification of immunologic reactions using catalytic deposition at the
      reaction sites of tyramine derivatives. A decisive gain in sensitivity in
      immunohistochemistry and in situ hybridization].
AB  - In the catalyzed reporter deposition technique, horseradish peroxidase catalyzes
      the activation of conjugated phenolic compounds resulting in the covalent binding
      of the radicalized intermediates to electron rich moieties in the protein
      molecules present at the site of reaction. Comparing the biotinyl-, digoxigeninyl
      , and fluoresceinyl-derivatives of tyramine and four immunohistochemical formats,
      we showed that the most sensitive detection system was that using biotinyl
      tyramide and an immunohistochemical technique using a biotinylated secondary
      antibody followed by a streptavidin peroxidase. Amplification without background
      staining was obtained in most biotin rich tissues with digoxigeninyl-tyramide.
      With fluoresceinyl-tyramide, clear signal amplification was observed in the
      fluorescent microscope. Finally, when compared with standard methods, increased
      sensitivity was obtained with the fluorescent derivative for detection of
      hybridized sequences in interphase chromosomes.

PMID- 9162153
TI  - [Ki-67, marker of proliferation].

PMID- 9162154
TI  - [Segmental absence of colonic muscularis propria. Report of a case in an adult].
AB  - We report a case of segmental defect of colonic muscularis propria revealed by
      perendoscopic perforation in a 64-year-old woman. Segmental absence of intestinal
      musculature is well documented in new-borns and infants and is more frequent in
      small bowel. It is characterized by localised absence of muscularis propria
      without fibrous scar. The remaining layers of the bowel wall are intact. The
      pathogenesis of this lesion is discussed.

PMID- 9162155
TI  - [Carcinosarcoma of the submaxillary gland].
AB  - Salivary gland carcinosarcoma is a rare neoplasm, with a poor prognosis, that
      should not be confused with the more common carcinoma ex-pleomorphic adenoma, in
      which the epithelial component alone is malignant. The authors report one case of
      carcinosarcoma of the submandibular gland, with no previous history of pre
      existent tumor. The tumor exhibited two intermingled and very atypical cellular
      components, one undifferentiated and the other with a chondroid pattern.
      Immunostaining with epithelial markers in the undifferentiated area allowed to
      distinguish this tumor from salivary gland sarcomas. In addition, the positivity
      for EMA, vimentin, and S100 protein in the two predominant components suggested a
      common origin for the different tumoral cell types, and led to discuss the
      nomenclature and the still unclarified cellular origin of these tumors.

PMID- 9162156
TI  - [Rare non-Hodgkin's lymphoma in the course of infection with human
      immunodeficiency virus. Two cases with bone marrow invasion].
AB  - Malignant non Hodgkin's lymphomas in patients with acquired immunodeficiency
      syndrome are usually of high grade and have a B-cell phenotype. We describe two
      cases of rare lymphomas during acquired immunodeficiency syndrome: one case of
      pleomorphic T cell lymphoma with medium and large cell predominance, of high
      grade of malignancy, according to the updated Kiel classification, involving
      mainly the bone-marrow, and one case of low grade monocytoid B-cell lymphoma with
      bone-marrow extension, which is a rare condition in this type of lymphoma. These
      lymphomas seem to be a casual event during acquired immunodeficiency syndrome,
      but the immunodeficiency can be responsible of a more aggressive behavior.

PMID- 9162157
TI  - [Undifferentiated soft tissue tumor with rhabdoid phenotype (extra-renal rhabdoid
      tumor). Report of a congenital case associated with medulloblastoma in a
      brother].
AB  - We report a case of congenital cervical rhabdoid tumor with association of a
      medulloblastoma in a brother. The immunohistochemical features of this tumor are
      compatible with a neuroectodermal differentiation (MIC 2+, Leu 7+). Extrarenal
      rhabdoid tumors share a common morphology but do not represent a single entity
      with only one histogenesis. Most of them are now considered to be of
      neuroectodermal origin. In our case, the association with a medulloblastoma in a
      brother seems to confirm this concept.

PMID- 9162158
TI  - [Congenital asplenia. A childhood immune deficit often detected too late].
AB  - We report a case of fatal pneumococcal sepsis in a previously healthy 22 month
      old child. At postmorten examination the patient was found to have an atrophic
      spleen. When other malformations are not associated, congenital asplenia is
      generally diagnosed after death related to pneumococcal infection.

PMID- 9162159
TI  - [Retiform hemangioendothelioma].
AB  - Hemangioendotheliomas are vascular tumors of intermediate malignancy considered
      as low-grade angiosarcomas. The authors report two cases of a distinctive type,
      named retiform hemangioendothelioma because of its particular morphologic
      features, and recently delineated by Calonje and al. This tumor of the skin
      recurs frequently but has a very low metastatic rate.

PMID- 9162160
TI  - [Eccrine syringofibroadenoma. Report of a case].
AB  - Eccrine syringofibroadenoma is an uncommon benign adnexal tumor (about thirty
      reported cases). Its clinical presentation is variable and non specific. The
      diagnostic is never evident before histological exam. Histologically it is an
      epithelial proliferation organized in thin cords appended to the epidermis with
      cuticular differentiation. Eccrine poroma and fibroepithelial tumor of Pinkus are
      the main histological diagnostic problems. The authors report two new cases in
      two women of 35 and 69 years which had been clinically considered as
      histiocytofibroma and molluscum pendulum.

PMID- 9162161
TI  - [A recurrent subcutaneous nodule in an infant].

PMID- 9162162
TI  - [Blastic lymphoid cells in the bone marrow of an infant].

PMID- 9162163
TI  - [An umbilical nodule to be considered religiously].

PMID- 9162164
TI  - [Flow cytometry measurement of DNA fragmentation in the course of cell death via
      apoptosis. New techniques for evaluation of DNA status for the pathologist].
AB  - Cell death by apoptosis is characterized by DNA fragmentation in 200-250 and/or
      30-50 kb followed or not by internucleosomal DNA fragmentation in 180-200 pb.
      Such characteristics have been used to distinguish between necrotic and apoptotic
      cells, and also to identify and quantify apoptotic cells by flow cytometry. In
      the case of internucleosomal DNA fragmentation, the analysis of DNA content
      constitutes the easiest method to identify apoptotic cells giving an hypoploid
      cell population commonly called "Sub G1". The identification of the "Sub G1" does
      not depend on the dyes used; however according to the method of cell fixation and
      permeabilization, of the divalent cations (Ca2+, Mg2+) present in the staining
      buffers and of the use of trypsin, the "Sub G1" population may be more or less
      difficult to identify. To detect apoptotic cells whatever the pattern of DNA
      fragmentation, the most commonly used methods are either in situ nick-translation
      or TUNEL (TdT dUTP Nick End Labelling). Thus, flow cytometry offers a wide range
      of attractive techniques to characterize apoptotic cells but it requires the use
      of methodological controls for validating results.

PMID- 9162165
TI  - [Monitoring of the margins of excision of skin tumors].

PMID- 9162167
TI  - [Primary meningioma of the scalp. Report of a case].

PMID- 9162166
TI  - [Pelvic metastases revealing infiltrating lobular carcinoma of the breast].

PMID- 9162168
TI  - [A new prognostic classification of thymomas].

PMID- 9162169
TI  - [The PRINS technique. A new strategy for in situ chromosome detection].

PMID- 9162171
TI  - Effects of fraxetin on glutathione redox status.
AB  - We have evaluated the effects of an oral treatment of mice with fraxetin (25
      mg/kg for 30 days) on the glutathione system (GSH, GSSG, and GSSG/GSH ratio as
      stress index), glutathione reductase (GR) and glutathione peroxidase (GPx) in
      liver supernatants from male C57BL/6J mice (18-month old). A significant
      antioxidant effect in vivo was found under this treatment by a decrease in the
      GSSG/GSH ratio and an increased activity of GR compared with the control mice.
      GSSG rate and GSSG/GSH ratio were correlated with the decline of GPx++ activity.
      Our results of increased GR activity could be considered as a supercompensation
      in glutathione redox status that involves a decrease in the accumulation of GSSG,
      as well as, in GSSG/GSH ratio. Finally, we suggest that this possible mechanism
      of supercompensation could lead to an enhancement in the average life span.

PMID- 9162170
TI  - Cytotoxicity and antitumor activity of platinum (II) complexes of aromatic and
      cycloalkanecarboxylic acid hydrazides.
AB  - New platinum (II) complexes of cyclohexanecarboxylic acid hydrazide (chcah) were
      synthesized and characterized by elemental analysis, IR, and 1H NMR spectra.
      Their inhibitory effects on cell growth and macromolecular synthesis of Friend
      leukemia cells in culture as well as the in vivo antitumor activity towards L1210
      leukemia in mice were compared with those of complexes containing differently
      substituted aromatic acid hydrazides. Some of the complexes exhibited
      antineoplastic activity. No correlation between the in vivo cytotoxicity and the
      in vivo antitumor activity was found. However, there was a relationship between
      the in vitro macromolecular synthesis inhibition profile and the in vivo
      antineoplastic effect, similar to that of cisplatin. On the other hand, only
      agents containing one amine ligand were active in vivo. The substitution of the
      aromatic ring by a cycloalkane residue increased significantly the antitumor
      effect, with [Pt(NH3)(chcah)Cl2] being the most active compound in this study.

PMID- 9162172
TI  - Plural origins of molecular homochirality in our biota Part II. The relative
      stabilities of homochiral and mixed oligoribotides and peptides.
AB  - By computer simulations--molecular mechanics and molecular dynamics with the
      amber force field (Weiner et al, (1986), J. Comp. Chem. 7, 230-252)--we have
      determined the stabilities of oligoribotide strands built with D- and L-riboses,
      and of peptide chains with D- and L-amino acid residues. In particular,
      complementary double-chains of oligoribotides were studied, since they are an
      important feature of the growing mechanism of modern nucleic acids. Peptide
      chains on the other hand, grow without need of a template. We found that mixed
      oligoribotides are less stable than homochiral ones, and that this chiral effect
      is less noticeable in peptide chains. The results support the interpretation that
      L-riboses act as terminators to the template-assisted growth of oligo-r-GD
      (enantiometric cross-inhibition; Joyce et al., (1987), Proc. Natl. Acad. Sci. USA
      84, 4398-4402). Based on this effect, a chemical pathway is proposed which could,
      under assumed prebiotic conditions, bypass the hindrance of homochiral growth.

PMID- 9162173
TI  - [Importance of in vivo and in vitro studies of leukotrienes. Application to the
      particular instance of aspirin].
AB  - The major role played by leukotrienes in the inflammatory reaction is today
      clearly demonstrated. These newly-formed mediators show powerful pro-inflammatory
      activities and their release from various cell types may be induced by agonists
      including the allergens. Therefore, leukotriene levels in biological fluids may
      represent a reliable image of the local or systemic inflammatory reaction and
      their release in vitro after incubation of the blood leukocytes in the presence
      of a specific allergen is today widely used for allergy diagnosis. Leukotrienes
      metabolism is deeply involved in aspirin intolerance or so-called pseudo allergy
      and, in spite of that the exact mechanism involved is still unknown, leukotriene
      release in vitro by ASA in the presence C5a represent the first reliable test for
      this diagnosis. The results of the recent clinical trials concerning the activity
      of anti-leukotrienes in vivo have led to a real therapeutic hope.

PMID- 9162174
TI  - [Clinico-immunological study of 16 cases of benzoate intolerance in children].
AB  - The authors report a sery of 16 cases of intolerance to the benzoates in
      children. Sixteen children (9 boys and 7 girls) were directed to the Hospital of
      Tarbes from June 1995 to July 1995, for recurring urticaria (7/16) combined with
      asthma (1/16), atopic eczema (2/16), dermorespiratory syndrome (2/16) and asthma
      (1/16). All were subject to an immunological examination comprising alimentation
      inquiry, prick test, IgE determination, RAST, oral provocation test to benzoates,
      which establishes the diagnosis, whose confirmation is certified by the benefit
      of the food eviction. To conclusion, the authors underline several points: the
      presumable underestimation of the intolerance, the often mentioned atopic
      familial context, the observed pathology (urticaria, asthma, eczema), the
      importance of the provocation test. Finally, besides food such as grey shrimps,
      sodas and antibiotic syrups, one finds benzoates in the antiallergic syrups
      initially prescribed as a preventive measure.

PMID- 9162176
TI  - [Hepatitis C: screening and treatment].

PMID- 9162175
TI  - [Does the pork/cat syndrome constitute a predisposition to heparin allergy?].
AB  - Observations are reported of two heparin-allergic patients (in one case,
      urticaria and in the other urticaria and asthma). These two patients show a
      curious association of the pork/cat syndrome, previously described (1, 2), that
      is an association of sensitivity to cat epithelia and pork meat. Since the
      heparins used nowadays are of porcine origin, the question is raised of a
      possible causal link that may exist between these 2 allergies. It seems that the
      possibility of association of these two allergies is much more likely than chance
      encounter.

PMID- 9162177
TI  - A bioactive triterpene from Lantana camara.
AB  - Lantana camara afforded a novel triterpene 22 beta-acetoxylantic acid and the
      known triterpenes, lantic acid, 22 beta-dimethylacryloyloxylantonolic acid, a
      mixture of 22 beta-dimethylacryloyloxy lantanolic acid and 22 beta
      angeloyloxylantanolic acid and lantanolic acid. 22 beta-Acetoxylantic acid showed
      antimicrobial activity against Staphylococcus aureus and Salmonella typhi. This
      compound and 22 beta-dimethylacryloyloxy lantanolic acid also showed
      antimutagenic activity.

PMID- 9162179
TI  - [Clinical considerations of cases of biliary ileus].
AB  - The authors report 6 cases of gallstone ileus due to cholecystoduodenal fistula.
      In 4 patients a simple enterolithotomy was performed, while in one case the
      enterolithotomy was associated to cholecystectomy and duodenal suture; in the
      last patient it was associated to cholecystectomy and gastric resection. Only one
      death was registered among the cases treated with enterolithotomy. The authors
      believe that the severity of the pathology, generally combined with other
      important diseases, needs an eclectic treatment depending on the patient status.

PMID- 9162178
TI  - [The current state of surgery in severe obesity: the advent of laparoscopy].

PMID- 9162180
TI  - [Foreign bodies in the gastrointestinal tract. Our cases and a review of the
      literature].
AB  - The ingestion or introduction of foreign bodies is a common situation in
      emergency surgery. The patients who usually ingest foreign bodies for different
      reasons are children, psychotics, alcoholics, prisoners and old people. The
      authors analyzed 65 cases observed in the I Institute of Surgery of the
      University of Rome "La Sapienza": 45 males and 20 females. Both the anal
      introduction and ingestion may be accidental or voluntary. The incidence of
      complications is estimated about 5 to 7%. The authors underline the opportunity
      of a conservative removal through endoscopic procedures especially for
      intraesophageal corps. This procedure is recommended to reduce morbidity and
      mortality rates, as well as hospitalization and social costs.

PMID- 9162181
TI  - [Postoperative chylous ascites: its etiology and treatment].
AB  - Postoperative chylous ascites is a rare clinical condition that occurs as a
      consequence of disruption of the abdominal lymphatics after retroperitoneal
      dissection. Generally the management is conservative based on a low fat diet and
      total parenteral hyperalimentation. However, such therapy requires weeks to
      months before resolution of the ascites. On the other hand, surgical approach is
      associated with a high failure rate to ligate leaky lymphatics. The Authors,
      therefore suggest a surgical resolution of the ascite with the use of fibrin glue
      to occlude rapidly and permanently the lymphatics ruptured.

PMID- 9162182
TI  - [Carcinoma of the extrahepatic bile ducts].
AB  - In the last 5 years 25 patients (11 men, 14 women) with carcinoma of the
      extrahepatic biliary duct were studied. The most frequent localization of the
      carcinoma was the hepatic hilum. D.C.P. according to Whipple was possible only in
      one patient, while in 20 patients a palliative approach with external and
      internal biliary derivations was the choice. In the remaining 4 patients an
      explorative laparotomy with biopsy was performed. It is concluded that palliative
      resection allows for a better quality of life.

PMID- 9162183
TI  - [Hepatic cysts: a case report and anatomicopathological and clinico-therapeutic
      considerations].
AB  - The recent observation of a case of non-parasitic cyst of the liver brought the
      authors to a literature review. A 62 year old male, affected by type 2 diabetes
      and hypertension, after a CT scan and ETG, underwent resection and "capitonnage"
      of the cyst. Three months after surgery a CT scan showed a complete repletion of
      the cavity previously occupied by the cyst as a consequence of regeneration and
      reorganization of the hepatic parenchyma. In conclusion, hepatic cysts are rare
      and clinically relevant only when huge. The diagnosis is possible with the use of
      ETG and CT scan of the abdomen, however, in some cases angiography is also
      useful. The intervention of choice is the "capitonnage" of the cyst.

PMID- 9162184
TI  - [Localized fibroma: a rare tumor of pleural origin].
AB  - Localized fibroma represents a rare entity arising from the pleura. Currently its
      histogenesis and clinical behaviour are still controversial. A case of a 64-year
      old male is here presented; clinical and histopathological features are then
      discussed on the basis of a review of the Literature. At present, an en-bloc
      resection of the tumor, including wide margins of the surrounding lung tissue,
      seems to be the most appropriate surgical choice.

PMID- 9162185
TI  - [Plastic surgery in the treatment of the outcome of intestinal bypass for
      obesity: a clinical case report].
AB  - The authors report the case of a 39-year old woman who had a fast and dramatic
      weight loss after an intestinal bypass performed elsewhere. The result was a
      generalized skin flakiness which caused dissatisfaction and psychological
      unbalance of the patient. Three plastic surgeries were therefore programmed and
      performed at different moments: mastopexy, abdominoplasty and upper thigh
      dermolipectomy. No immediate or late complications were observed, even after 2
      years. The authors stress the importance of a correct planning of a plastic
      surgery as a solution to the generalized tissue flakiness in the formerly obese
      patient.

PMID- 9162186
TI  - [A 3-year experience of the repair of voluminous abdominal laparoceles with
      patches of prosthetic material].
AB  - The authors deal with huge ventral hernias having a defect of more than 10 cm in
      diameter. They report 16 cases in three years of experience: 10 treated with
      Marlex patches and 6 treated with Goretex prosthetic material.

PMID- 9162188
TI  - [Treatment via laser of airway obstructions].
AB  - The Nd-YAG laser is widely used in endoscopy. Laser therapy either by contact or
      non-contact method, can be considered the best palliative option for patients
      affected by airway obstruction due to endoluminal malignant tumours. It aims at
      the improvement of breathing conditions and symptomatology. In patients affected
      by benign obstructions, it often allows to obtain curative results avoiding the
      use of traditional surgery. From 1988 to 1993 at the First Department of Surgery
      of the University of Rome "La Sapienza", 163 treatments out of 111 clinical cases
      affected by airway obstruction, caused by malignant tumours considered inoperable
      or relapsed after operation, or by vegetating benign tumours, or granulomas or
      fibrous diaphragms were performed. The symptomatological improvement and
      beneficial changes in functional breathing tests, haemogasanalysis, and X-ray
      findings were registered 24-48 hours after each treatment. The results showed an
      improvement in functional breathing values especially after treatment of the main
      airways such as trachea and main bronchi. The therapy offered an acceptable
      quality of life. A fairly good number of patients may also return to radio and
      chemotherapy, if previously interrupted.

PMID- 9162187
TI  - [The endoscopic treatment of postoperative stenoses of the upper digestive
      tract].
AB  - The authors compare their experience in dilatation of postoperative benign
      esophageal strictures. A total of 60 patients (37 males, 23 females: mean age
      52), all with severe dysphagia, from January 1985 to September 1995, underwent
      endoscopic dilatation: 32 of these with Savary dilators and 28 with balloon
      dilators. Dilatation was effective in 93% in both groups. Two severe
      complications were recorded (1 heart attack and 1 perforation) in the group that
      underwent endoscopic dilatation with Savary dilators. During endoscopic
      management, pain recurred in 43% and 87% of cases after balloon or Savary
      dilatations, respectively. The authors believe balloon dilators are more
      effective, better tolerated and with less complications than Savary dilators.
      They reserve the management with Savary dilators to the extremely severe
      esophageal strictures.

PMID- 9162189
TI  - [The intraoperative visualization of the bile ducts by the use of fluorescent
      substances. A feasibility study].
AB  - Iatrogenic bile duct injury during cholecystectomy is the most serious
      complication of this surgical procedure. Initial reports suggest that this
      complication is particularly problematic during laparoscopic cholecystectomy.
      Proper identification of biliary anatomy in the subhepatic region is the only way
      to avoid this severe complication. The potential benefit from a simple, reliable
      method for intraoperative delineation of biliary anatomy is self-evident. In this
      experimental work the Authors-study the possibility and the feasibility of
      intraoperative biliary tree imaging with two fluorescent molecules
      (rolitetracyclin and fluorescin).

PMID- 9162190
TI  - [An update on parathyroid surgery].
AB  - The operative management of patients with hyperparathyroidism is controversial.
      High rates of persistent hypercalcemia and postoperative hypoparathyroidism are
      seen in multiple hyperplasia and bilateral neck exploration. Patients undergoing
      unilateral neck exploration with removal of a single parathyroid adenoma have a
      rapid clearance of PTH which declines within hours after surgery. There is a
      sensitive immunometric assay (IRMA) for the intact molecule which demonstrates a
      decline in 15 minutes during surgery. Intraoperative measurement of PTH may be
      complementary to surgical skill and histopathologic information and may modulate
      extension of neck exploration.

PMID- 9162191
TI  - Cytogenetics and molecular genetics of carcinomas arising from thyroid epithelial
      follicular cells.
AB  - Cytogenetic and molecular analyses of thyroid tumors have indicated that these
      neoplasms represent a good model for analyzing human epithelial cell multistep
      carcinogenesis. They comprise, in fact, a broad spectrum of lesions with
      different phenotypes and variable biological and clinical behavior. Molecular
      analysis has detected specific genetic alterations in the different types of
      thyroid tumors. In particular, the well-differentiated carcinomas of the
      papillary type are characterized by activation of the receptor tyrosine kinases
      (RTKs), RET and NTRK1 proto-oncogenes. Cytogenetic analysis of these tumors has
      contributed to defining the chromosomal mechanisms leading to RTK oncogenic
      activation. In the majority of cases, intrachromosomal inversions of chromosome
      10 and chromosome 1 led to the formation of RET-derived and NTRK1-derived
      oncogenes, respectively. Interestingly, molecular analysis of these oncogenes
      revealed their nature of chimeric fusion proteins all sharing the tyrosine kinase
      (TK) domains of the respective proto-oncogenes. Moreover, the sequencing of the
      oncogenic rearrangements led to the identification of a breakpoint cluster region
      in both RTK proto-oncogenes. Exposure to ionizing radiation is associated with
      papillary carcinomas and RET activation has been suggested to be related to this
      event. Conversely, RAS point mutations are frequently observed in tumors with
      follicular histology and have been associated with metastatic dissemination.
      Iodide-deficient areas seem to provide a higher frequency of RAS positive
      follicular carcinomas. Finally, a high prevalence of TPS3 point mutations has
      been detected only in undifferentiated or anaplastic carcinomas and found to
      correlate inversely with 8CL2 expression. All of these findings are contributing
      to the definition of genetic and environmental factors relevant for the
      pathogenesis of thyroid tumors. Moreover, the characterization of specific
      genetic lesions could provide significant molecular tools for a better
      differential diagnosis and for the development of novel therapeutic avenues for
      thyroid cancer.

PMID- 9162192
TI  - Deletion of 1p36 in childhood endodermal sinus tumors by two-color fluorescence
      in situ hybridization: a pediatric oncology group study.
AB  - Childhood endodermal sinus tumors (CESTs) are a unique category of germ cell
      tumors involving the testis and extragonadal region in children less than 4 years
      of age. Recent studies of CEST have shown recurrent cytogenetic abnormalities
      involving the short arm of chromosome 1, most commonly, a deletion of distal 1p.
      Experience with neuroblastomas has shown that cytogenetic analyses may
      underestimate the frequency of 1p deletion. To determine the frequency of
      deletion of Ip in CEST and to verify that 1p is, in fact, deleted and not
      translocated, we analyzed ten tumors by two-color fluorescence in situ
      hybridization on single-cell suspensions of interphase nuclei by using a cosmid
      probe from the PITSLRE kinase (p58) locus (previously mapped to 1p36)
      cohybridized with plasmid probe pUC1.77 (which recognizes the 1q heterochromatic
      region) to determine the copy number of chromosome 1. Eight of the ten tumors
      examined showed evidence of deletion of 1p36. Five of the eight tumors exhibited
      multiple subdones, and all subdones showed deletion of at least one copy of 1p36,
      indicating that the deletion probably occurred before the development of
      chromosome 1 aneusomy. We conclude that deletions of the short arm of chromosome
      1, specifically 1p36, do occur in CEST and probably occur at a, higher incidence
      than that found in neuroblastoma Further studies are needed to determine the
      degree of overlap of the common area of deletion in CEST with that of
      neuroblastoma and to determine whether 1p deletion in CEST has prognostic
      significance.

PMID- 9162193
TI  - Molecular heterogeneity of B-lineage diffuse large cell lymphoma.
AB  - B-lineage diffuse large cell lymphoma (B-DLCL) arising de novo is characterized
      by a marked degree of clinical heterogeneity. To determine whether or not the
      clinical heterogeneity of de novo B-DLCL is reflected by heterogeneity in the
      molecular features of these tumors, we investigated the pattern of distribution
      of several genetic lesions in 70 cases of de novo B-DLCL at diagnosis. The panel
      of genetic lesions tested comprised the molecular alterations most frequently
      detected in B-DLCL, including rearrangements of BCL2, BCL6, and MYC as well as
      deletions of 6q and mutations of TP53. One or more genetic lesions were detected
      in 39/70 cases of B-DLCL. Isolated structural alterations of BCL2, BCL6, 6q or
      TPS3 were detected in 8/70, 10/70, 11/70, and 3/70 cases, respectively. No
      isolated MYC lesions were detected. Six cases carried different combinations of
      two genetic lesions, including lesions of BCL2 + BCL6 (1 case), BCL2 + MYC (1
      case), BCL2 + 6q (2 cases), or BCL6 + 6q (2 cases). One case had accumulated
      three genetic lesions, namely a rearrangement of BCL2 and BCL6 and a mutation of
      TPS3. Overall, these data show that multiple distinct patterns of genetic lesions
      may associate with de novo B-DLCL, indicating that the molecular pathogenesis of
      this group of lymphomas is characterized by a high degree of molecular
      heterogeneity.

PMID- 9162194
TI  - Ring chromosomes in parosteal osteosarcoma contain sequences from 12q13-15: a
      combined cytogenetic and comparative genomic hybridization study.
AB  - Seven parosteal osteosarcoma (POS) samples, six of which were cytogenetically
      characterized, were studied by using comparative genomic hybridization (CGH). All
      samples showed DNA sequence copy number changes (mean, six aberrations/tumor;
      range, 1-13); gains were more frequent than losses. Gain of 12q13-15 sequences
      was found in every tumor and correlated with the presence of ring chromosomes.
      High-level amplification, which was detected in four tumors, was seen only in
      chromosome 12, with 12q13-14 as the minimal common region. By using chromosome
      painting, one of the rings of one case was shown to be composed entirely of
      chromosome 12 material. Together with previous data, our findings show that gain
      of 12q13-15 sequences is a characteristic feature of POS and that these sequences
      are contained within the ring chromosomes.

PMID- 9162195
TI  - Detection of frequent allelic loss of 6q23-q25.2 in microdissected human breast
      cancer tissues.
AB  - Detection of allelic loss in human breast cancer is hindered by the fact that
      breast cancer tissues are frequently infiltrated by stromal and inflammatory
      cells. For this study, we carefully microdissected infiltrating breast cancer
      tumor cells from contaminating normal cells and analyzed the DNA from these
      samples for allelic loss on the long arm of chromosome 6 by using a panel of 15
      dinucleotide repeat markers. We found 53 of the 66 cases studied (80%) to have
      allelic loss of either the entire chromosomal arm (37 cases) or a portion of the
      chromosomal arm (16 cases). One common region that was identified for all tumors
      with deletions of 6q was the area between markers D6S310/314 and D6S473/255,
      consistent with a tumor suppressor gene locus at 6q23-6q25.2. The use of tissue
      microdissection allowed the detection of allelic loss in this chromosomal region
      in human breast cancer at a much higher frequency than was previously recognized.

PMID- 9162196
TI  - Probes for hidden hyperdiploidy in acute lymphoblastic leukaemia.
AB  - The detection of hyperdiploidy (clones with >46 chromosomes) in the bone marrow
      of patients with acute lymphoblastic leukaemia (ALL) is important because of the
      prognostic impact of this finding. The high hyperdiploid (HeH) subgroup with 51
      68 chromosomes is associated with the best outcome, followed by the low
      hyperdiploid (HeL) subgroup with 47-50 chromosomes and the triploid/tetraploid
      (TT) subgroup with >68 chromosomes, which do less well. We present a strategy for
      the use of fluorescence in situ hybridization (FISH) with chromosome-specific
      probes to detect hyperdiploidy in interphase cells and to assign cases to a
      ploidy subgroup. By using a model population of 252 cases, it was seen that ten
      chromosomes (X, 4, 6, 8, 10, 14, 16, 18, 20, and 21) used in particular
      combinations and applied in a step-wise manner enabled the detection of 94% of
      hyperdiploid cases and gave an accurate prediction of ploidy subgroup in 96% of
      these cases. The detection and classification of each case required the use of
      four to six probes over two or three steps. Confirmation that this strategy will
      achieve this level of detection in other hyperdiploid populations was
      demonstrated by using 250 published karyotypes. This strategy has an application
      in detecting missing or hidden hyperdiploid cases among cases with failed or
      normal cytogenetics.

PMID- 9162197
TI  - Overrepresentation of 3q and 8q material and loss of 18q material are recurrent
      findings in advanced human ovarian cancer.
AB  - In order to define the ability of comparative genomic hybridization (CGH) to
      detect and map genetic imbalances, we investigated 47 malignant ovarian tumors
      and 2 ovarian tumors of low malignant potential. The most common genetic changes
      in order of frequency included DNA gains of chromosome arms 8q (53%), 3q (51%),
      20q (43%), 1p (32%), 19q (30%), 1q (28%), 12p (28%), 6p (21%), and 2q (19%). The
      smallest regions of overrepresentation could be defined in 3q26-qter, 8q23-qter,
      1p35-pter, 12p 12, and 6p21-22, respectively. Losses were detected on 18q (23%),
      chromosome 4 (23%), 13q (17%), and 16q (17%) with the smallest underrepresented
      regions on 18q22-qter, 13q21, and 16q23-qter. Also, losses of the X chromosome
      (19%) were detected, correlating with higher ages of the patients. Therefore,
      some of these X chromosome losses might be due to a well-known aging phenomenon
      and in these cases will be more preferably lost during cell division and tumor
      progression. Our findings show that ovarian carcinomas reveal consistent
      chromosomal abnormalities. Further detailed studies of these regions with
      specific molecular genetic techniques may lead to the identification of oncogenes
      and/or tumor suppressor genes playing an important role in the tumorigenesis of
      ovarian carcinomas.

PMID- 9162198
TI  - Evidence for two senescence loci on human chromosome 1.
AB  - Microcell-mediated introduction of a neo-tagged human chromosome 1 (HC-1-neo)
      into several immortal cell lines has previously been shown to induce growth
      arrest and phenotypic changes indicative of replicative senescence. Somatic cell
      hybridization studies have localized senescence activity for immortal hamster 10W
      2 cells to a cytogenetically defined region between 1q23 and the q terminus.
      Previous microcell-mediated chromosome transfer experiments showed that a
      chromosome 1 with an interstitial q-arm deletion (del-1q) lacks senescence
      inducing activity for several immortal human cell lines that are sensitive to an
      intact HC-1-neo. In contrast, our studies reveal that the del-1q chromosome
      retains activity for 10W-2 cells, indicating that there are at least two
      senescence genes on human chromosome 1. Sequence-tagged site (STS) content
      analysis revealed that the q arm of the del-1q chromosome has an interstitial
      deletion of approximately 63 centimorgans (cM), between the proximal STS marker
      DIS534 and distal marker DIS412, approximately 1q12 to 1q31. This deletion
      analysis provides a candidate region for one of the senescence genes on 1q. In
      addition, because this deletion region extends distally beyond 1q23, it localizes
      the region containing a second senescence gene to approximately 1q31-qter,
      between DIS422 and the q terminus. STS content analysis of a panel of 11 10W-2
      microcell hybrid clones that escaped senescence identified 2 common regions of
      loss of 1q material below the distal breakpoint of del-1q. One region is flanked
      by markers DIS459 and ACTN2, and the second lies between markers WI-4683 and
      DIS1609, indicating that the distal 1q senescence gene(s) localizes within 1q42
      43.

PMID- 9162199
TI  - Loss of heterozygosity studies indicate that chromosome arm 1p harbors a tumor
      supressor gene for renal oncocytomas.
AB  - We carried out a complete genome scan for loss of heterozygosity (LOH) in four
      renal oncocytomas by using highly polymorphic CA repeat microsatellite loci.
      Three of the four tumors exhibited LOH for chromosome arm 1p, and the oncocytomas
      of both female patients lost Xq. Therefore, these chromosome arms may harbor
      tumor suppressor genes involved in the etiology of this disease. Although the
      genomes of ontocytomas are relatively stable, two different microsatellite loci
      in one tumor were mutated by + or - 2 nt. Similar alterations in CA repeats that
      are probably due to spontaneous mutation have been observed in renal cell
      carcinomas.

PMID- 9162200
TI  - Observation of a deletion of the long arm of chromosome 6 in benign fibrocystic
      disease of the breast constitutes a challenging problem.
AB  - We observed an interstitial deletion of the long arm of chromosome 6 occurring as
      the sole anomaly in a benign fibrocystic disease of the breast, confirming its
      nonrandom occurrence in this type of condition, and we discuss the possible
      meaning of this observation.

PMID- 9162201
TI  - Different cytogenetic patterns in skeletal breast cancer metastases.
AB  - Short-term cultures of breast cancer metastases to bone from two patients were
      analyzed cytogenetically. One metastasis had a complex hypotriploid karyotype
      with numerous marker chromosomes, whereas the other had simple karyotypic changes
      in three unrelated clones, 46,XX,t(4;11 )(p14;p 13)/45,XX,- 19/46,XX,del(3)(p
      13p23), suggesting that the metastasis had originated from a simultaneous
      invasion of multiple cells from the primary tumor. The metastasis with complex
      chromosomal aberrations developed quickly as part of a clinically aggressive
      disease, whereas that with simple changes developed more than 20 years after the
      initial breast cancer diagnosis. Our findings therefore indicate that the tumor
      karyotype may play a role in determining the clinical course in patients with
      breast cancer.

PMID- 9162202
TI  - CSF of neuroleptic-naive first-episode schizophrenic patients: levels of biogenic
      amines, substance P, and peptides derived from chromogranin A (GE-25) and
      secretogranin II (secretoneurin).
AB  - Lumbar cerebrospinal fluid (CSF) was collected from controls and neuroleptic
      naive patients with their first acute schizophrenic episode. The CSF was analyzed
      for several biogenic amines and their metabolites [dopamine,dihydroxyphenylacetic
      acid (DOPAC), noradrenaline, 5-hydroxytryptamine (5-HT), 5-hydroxyindolacetic
      acid (5-HIAA)]. For these transmitters, which are stored and secreted from
      synaptic vesicles, there was no significant difference between controls and
      schizophrenic patients. As constituents of large dense-core vesicles substance P
      (SP) and GE-25 (derived from chromogranin A)-and secretoneurin (derived from
      secretogranin 11)-immunoreactivities were determined. SP-like immunoreactivity
      levels did not differ between controls and patients; however, GE-25 was elevated
      and especially the GE-25/secretoneurin ratio was significantly (p < .001) higher
      in patients. Characterization of the immunoreactivities by high-performance
      liquid chromatography did not reveal any difference between patients (n = 3) and
      controls in the processing of the two proproteins chromogranin A and
      secretogranin II. These data indicate that proteolytic processing of the two
      widespread constituents of large dense-core vesicles, i.e., chromogranin A and
      secretogranin II, is not altered in schizophrenic patients. The increase in the
      chromogranin A /secretoneurin ratio in schizophrenic patients deserves further
      investigation in order to elucidate its possible pathogenetic significance.

PMID- 9162203
TI  - Autoradiography with [3H]8-OH-DPAT reveals increases in 5-HT(1A) receptors in
      ventral prefrontal cortex in schizophrenia.
AB  - We previously reported increased glutamatergic innervation in orbital frontal
      cortex in schizophrenia. In view of the evidence that one serotonin (5-HT)
      receptor, the 5-HT(1A) subtype, is associated with cortical glutamatergic
      neurons, we have used quantitative receptor autoradiography to measure the
      specific binding of the 5-HT(1A) receptor ligand [3H]8-OH-DPAT (2 nM) in sections
      of orbital frontal cortex taken from 18 control and 12 schizophrenic postmortem
      brains. Schizophrenic patients, as compared with controls, had increased 5-HT(1A)
      receptor binding in the three orbital frontal regions examined. These effects
      were pronounced in the male subgroup, and were most apparent in the outer
      cortical laminae. These data are consistent with the hypothesis that
      schizophrenia is associated with an abnormal glutamatergic afferent innervation
      of orbital frontal cortex.

PMID- 9162204
TI  - Semantic memory is impaired in schizophrenia.
AB  - Memory is emerging as a key area of neuropsychological deficit in schizophrenia,
      with evidence suggesting that the impairment is restricted to long-term memory.
      Semantic memory, the component of long-term memory containing stored
      representations of the meanings of words and knowledge about the world, was
      examined in 46 schizophrenic patients and 40 normal controls using a recently
      devised battery of tests. Evidence of semantic memory impairment was found which
      was wide ranging and substantial; in some cases it approached the levels seen in
      a group of 22 patients with mild-to-moderate Alzheimer's disease. Both group
      analysis and a more detailed examination of two single cases suggested that
      semantic memory impairment represents a disproportionate and possibly specific
      neuropsychological deficit in schizophrenia.

PMID- 9162205
TI  - Reduction in hippocampal formation volume is caused mainly by its shortening in
      chronic schizophrenia: assessment by MRI.
AB  - We performed contiguous, 1 mm thick, magnetic resonance imaging scans in 18 men
      with chronic schizophrenia and in 18 age-matched healthy subjects to test in
      living patients the findings of a previous postmortem study. The schizophrenic
      patients showed bilaterally shortening (left, -6%; right, -9%) and volume
      reduction (left, -9%; right, -11%) of the hippocampal formation (HF). Volumes of
      HF correlated positively with HF length in the schizophrenic patients. The
      reduction in bilateral HF volumes was small after controlling for HF lengths
      (left, -3%; right, -3%). In schizophrenic patients, significant negative
      correlations were found bilaterally between the length of HFs and the scores for
      attention, bizarre behavior, and positive formal thought disorder. The results
      suggest that the volume reduction seen in the HFs of schizophrenic patients was
      caused mainly by a shortening of the HF and that these clinical symptoms may be
      associated with shorter HF length.

PMID- 9162206
TI  - Salivary flow-rate and composition in schizophrenic patients on clozapine:
      subjective reports and laboratory data.
AB  - The extent of hypersalivation was evaluated in a group of 25 schizophrenic
      patients on clozapine. A high prevalence of the complaint was detected by a
      questionnaire; up to 80% of the patients complained of hypersalivation at night.
      Salivary flow-rate and composition was examined in 17 patients who agreed to
      participate and in a matched group of healthy controls. No significant
      differences were detected in composition or flow-rates of resting and stimulated
      saliva. The salivary flow-rates in the schizophrenic patients on clozapine did
      not correlate with the subjective complaint of hypersalivation. Because the
      severity and prevalence of the complaint was higher at night, a possibility of an
      altered circadian rhythm of salivation might be suggested in these patients.

PMID- 9162207
TI  - Course of panic disorder during pregnancy and the puerperium: a preliminary
      study.
AB  - Pregnancy has been referred to as a time of well-being for patients with
      psychiatric disorder. However, this impression is derived primarily from
      anecdotal reports and retrospective studies, rather than systematic prospective
      evaluation. In this study, 10 pregnant women with previous histories of panic
      disorder were evaluated prospectively across pregnancy and the postpartum period
      using the Structured Clinical Interview for DSM-III-R and the Clinical Global
      Impression. Information regarding pharmacotherapy received was also recorded.
      Seven of 10 subjects continued to meet DSM-III-R criteria for panic disorder at
      all trimester visits. Symptoms persisted for some patients even in the context of
      treatment with antipanic medications. Most subjects (n = 9) met DSM-III-R
      criteria at 1-3 months postpartum despite nearly uniform intensification of
      antipanic treatment. Although some women may experience diminished symptoms of
      panic during pregnancy, in this sample most continued to experience panic attacks
      and to require antipanic treatment to control symptoms.

PMID- 9162208
TI  - Cocaine abusers have reduced auditory P50 amplitude and suppression compared to
      both normal controls and alcoholics.
AB  - The auditory P50 evoked response to click stimuli was recorded from 10 2-week
      abstinent African-American chronic cocaine abusers and 10 African-American non
      substance-abusing controls. Stimuli consisted of pairs of clicks with a 500-msec
      interval between clicks in a pair, and a 7-8 sec interval between pairs of
      clicks. After averaging responses to 100 pairs of clicks and digital bandpass
      filtering between 10 and 50 Hz, P50 amplitude to the first and the second click
      was measured. The conditioning/testing (C/T) ratio, an index of P50 suppression,
      was computed as the ratio of P50 amplitude to the second compared to the first
      click. Chronic cocaine abusers had markedly diminished P50 amplitudes and
      increased C/T ratios (indicating decreased P50 suppression) in comparison to the
      controls. These P50 abnormalities were not seen in additional Caucasian
      gay/bisexual comparison groups of active alcoholics (n = 15) and non-substance
      abusing controls (n = 10). Thus, decrements in P50 amplitude and P50 suppression
      appear to be specific to cocaine abuse, and to differentiate cocaine abuse from
      alcohol abuse. A response analogous to P50 can be measured in animals,
      facilitating the development of animal models of this cocaine effect.

PMID- 9162209
TI  - Comparison of obsessions and compulsions in patients with anorexia nervosa and
      obsessive compulsive disorder.
AB  - Patients with anorexia nervosa (n = 18) and patients with obsessive-compulsive
      disorder (OCD) (n = 16) had similar scores on the Yale-Brown Obsessive Compulsive
      Scale (19 + or - 9 vs. 22 + or - 6). This suggests that these disorders have
      similar magnitude of impairment from obsessions and compulsions; however, OCD
      patients endorsed a wide variety of obsessions and compulsions, whereas anorexics
      tended to endorse symptoms that were related to symmetry and order.

PMID- 9162210
TI  - Involvement of the limbic system in multiple sclerosis patients with depressive
      disorders.
AB  - This study investigates the relationship between depression and both anatomic and
      cerebral blood flow abnormalities in multiple sclerosis (MS) patients. Ten
      nondepressed MS patients were compared with 10 depressed MS patients matched for
      age, sex, and functional disability. Both groups were evaluated by means of
      neuropsychological tests, magnetic resonance imaging, and single-photon emission
      tomography imaging. There was no difference between the two groups with regard to
      the global cognitive score. Magnetic resonance imaging data showed no significant
      differences in the number, side, location, and area of the demyelinating lesions
      between the two groups; however, regional cerebral blood flow asymmetries in the
      limbic cortex did distinguish the two groups. Analysis of variance showed a
      significant effect of depression on the perfusion asymmetries in the limbic
      cortex. Finally, perfusion asymmetries in limbic cortex significantly correlated
      with depression test scores. Our findings suggest that depression in MS patients
      could be induced by a disconnection between subcortical and cortical areas
      involved in the function of the limbic system.

PMID- 9162211
TI  - The predictive value of hypothalamic-pituitary-adrenal axis dysfunction in
      Alzheimer's disease.

PMID- 9162212
TI  - Carbamazepine and L-type calcium channel inhibitors: a binding assay study.

PMID- 9162213
TI  - Seasonal effects in prolactin response to m-chlorophenylpiperazine challenge in
      obsessive-compulsive disorder.

PMID- 9162214
TI  - Quantitative electroencephalographic frequencies and relative neuroleptic
      receptor affinities in schizophrenia.

PMID- 9162215
TI  - Cytokine induction by bacteria: beyond lipopolysaccharide.

PMID- 9162217
TI  - Reduced susceptibility to IL-1 and endotoxin in transgenic mice expressing IL-1
      in their lens.
AB  - To learn about the effects of chronic exposure to IL-1 we generated a transgenic
      (Tg) mouse line that expresses human IL-1 beta under the control of the lens
      alpha-A crystallin promoter. Expression of human IL-1 beta was restricted to the
      eye; neither the protein nor its mRNA were detected in various other organs of
      the Tg mice. The Tg mice develop severe ocular inflammation shortly after birth,
      which affects the lens and other eye tissues and apparently allows the release of
      IL-1 into the circulation. Here we report that the Tg mice exhibit decreased
      responsiveness to IL-1 and lipopolysaccharide (LPS), as compared to their wild
      type littermate controls: (1) when injected with IL-1 the Tg mice produced lower
      levels of serum amyloid A than their controls; (2) thymocytes of the Tg mice
      responded less vigorously in culture to stimulation with IL-1; and (3) Tg mice
      showed lower morbidity and mortality than their controls when injected with toxic
      amounts of LPS. These data suggest that chronic exposure to IL-1 in the Tg mice
      induces partial resistance to this cytokine, analogous to the reduced
      responsiveness to IL-1 in animals pretreated with this proinflammatory cytokine.

PMID- 9162216
TI  - Regulation of signal transducer, GP13O and the LIF receptor in acute inflammation
      in vivo.
AB  - Recently we examined the expression of the IL-6 receptor (gp80) in three
      different models of acute inflammation [Geisterfer et al., 1993, Cytokine 5:1].
      To continue these studies, we examined the mRNA expression of signal transducing
      molecule, gp130, and the LIF-R as associated members of a receptor family. Rats
      were treated with either Freund's complete adjuvant (FA) via intraperitoneal
      injection, LPS via intravenous injection, or turpentine via subcutaneous
      injection. The levels of gp130 and LIF-R mRNA expression had a maximum 2-3-fold
      increase over a 24 h period. However, the time of the maximum increase differed
      depending on the treatment the rats received. FA treated rats had a maximum
      induction of gp130 mRNA levels of 2.2-fold (for the 7.5 kb transcript) and 1.3
      fold (for the 9.0 kb transcript) at 12 h. LPS treated rats had a maximum increase
      at 3 h where message levels increased 2.5-fold (7.5 kb) and 1.2-fold (9.0 kb).
      Turpentine-injected rats showed little difference in gp130 mRNA levels at any
      time after injection compared to controls. Maximum LIF-R mRNA levels also
      differed depending on the type of treatment the rats received. FA-injected rats
      showed a 2.1-fold mRNA increase at 3 h, whereas LPS treated rats show a maximum
      2.4-fold increase at 18 h. Turpentine-injected rats showed little increase in
      mRNA levels compared to controls. Injection of purified recombinant rat IL-6 (rIL
      6) had little effect on LIF-R mRNA levels, but had a dramatic inducing effect on
      gp130 mRNA levels. Rats were also injected (i.p.) with Dexamethasone (Dex) and
      this had no effect on either gp130 or LIF-R mRNA level expression. These in vivo
      results indicated that IL-6 has a major role in the regulation of its own
      receptors, IL-6R (gp80), and gp130, and the onset of acute phase response. We
      found that the maximum IL-6R (gp80), gp130 and LIF-R mRNA levels peaked at
      different times depending on the type of acute inflammation induced in the rat.
      It seems that various combinations of cytokines and hormones are released
      depending on the type of acute inflammation, and these in turn regulate the
      expression of diverse receptors on the hepatocyte, resulting in different acute
      phase kinetics in the various models of inflammation.

PMID- 9162219
TI  - Proinflammatory cytokine production by human peripheral blood mononuclear cells
      stimulated with cell-free supernatants of Viridans streptococci.
AB  - Viridans streptococci (VS) have become recognized as an increasingly important
      cause of bacteraemia in neutropenic patients undergoing chemotherapy.
      Surprisingly, VS bacteraemia is associated with toxic shock-like syndrome (TSLS)
      and adult respiratory distress syndrome (ARDS), features not seen in non
      neutropenic patients with viridans streptococcal bacteraemia. The mechanism by
      which these Gram-positive bacteria cause hypo-tension in the absence of endotoxin
      is not known. In this study, we have analysed the ability of cell-free bacterial
      supernatants derived from VS to induce the production of a number of cytokines
      from human peripheral blood mononuclear cells (PBMC). These cytokines were tumour
      necrosis factor alpha (TNF-alpha), tumour necrosis factor beta (TNF-beta) and
      interleukin 8 (IL-8). All 59 strains were able to induce these proinflammatory
      cytokines. We conclude that VS do produce secreted products which are able to
      stimulate the production of cytokines which may be important in the pathogenesis
      of shock caused by these bacteria.

PMID- 9162218
TI  - Interleukin 4 suppresses primary interferon gamma response by T cells immunized
      in vivo and cultured in vitro with interleukin 2.
AB  - This paper describes a novel primary in vivo/in vitro culture system which allows
      analysis of the effect of IL-4 added to culture 1 day after immunization on the
      production of IFN-gamma. Mice are immunized epicutaneously with picryl chloride
      (TNP) and draining lymph node cells were harvested 1 day later. These cells (1
      day lymph node cells), when cultured in vitro for 3 days in the presence of IL-2,
      either continuously or as a pulse, give an IFN-gamma response on reexposure to
      antigen 3 days later. This production of IFN-gamma is both antigen-specific and
      genetically (MHC)-restricted and is due to both CD8+ and CD4+ T cells. However,
      if 1 day lymph node cells are cultured with both IL-2 and IL-4, no IFN-gamma is
      produced on subsequent reexposure to antigen, but the cells acquire the ability
      to produce IL-4 and IL-10. Moreover, cells pulsed with IL-4 blocked IFN-gamma
      production when cocultured with cells pulsed with IL-2. IL-4 only exerted its
      inhibitory activity on IFN-gamma production when added on the first or second day
      of culture and had no effect at later times. Finally, the inhibitory activity of
      IL-4 on IFN-gamma production may depend on the production of IL-10, induced by
      the IL-4, as the inhibitory effect of IL-4 is reversed by mAb against IL-10.

PMID- 9162220
TI  - Induction of CD25 expression in human B lymphocytes by pharmacological activators
      of cellular signalling pathways.
AB  - IL-4 promotes simultaneous expression of both the CD23 and CD25 antigens in
      resting human B lymphocytes in a dose-dependent manner. Simultaneous three-colour
      flow cytometric analysis revealed that CD19+/CD23+/CD25+ triple-positive cells
      were derived from a CD19+/CD23-/CD25- pool, and that induction of CD23 required
      lower doses of IL-4 than did induction of CD25. Although the concentrations of IL
      4 required for half-maximal up-regulation of CD23 (35 pM) and CD25 (150 pM)
      expression were different, the capacity of IL-4 to promote expression of the two
      markers could be mimicked by the same combination of pharmacological agents.
      Thus, maximal expression of CD23 and CD25 was obtained with a 30 (or 120) second
      pulse with phorbol ester and/or ionomycin followed by a sustained (20 minute)
      treatment with forskolin. Use of BAPTA to chelate intracellular calcium suggested
      that IL-4 driven CD25 expression required mobilization of intracellular Ca2+.
      Finally, down-regulation of cellular protein kinase C by chronic treatment of
      resting B lymphocytes with phorbol ester abolished the ability of IL-4 to elevate
      CD23 and CD25 expression; phorbol ester treatment similarly abrogated the ability
      of anti-CD40 and anti-Ig reagents to promote expression of CD25. The data are
      consistent with the proposal that IL-4 influences CD23 and CD25 expression via a
      similar signal transduction pathway which involves both protein kinase C
      activation and elevation of intracellular cAMP levels.

PMID- 9162221
TI  - Recombinant human granulocyte colony-stimulating factor reduces hepatitis C virus
      replication in mononuclear cells from chronic hepatitis C patients.
AB  - Hepatitis C virus infects mononuclear leukocytes of patients with chronic
      hepatitis C. Treatment with rhG-CSF led to a dose-related reduction in the
      genomic and antigenomic hepatitis C viral strands in cultures of mitogen
      stimulated, naturally-infected peripheral blood mononuclear cells from patients
      with chronic hepatitis C. Hepatitis C virus genomic strand of subtype 1b was
      suppressed in 5 of 11 cases, and concurrently with suppression of the viral
      antigenomic strand in two of them. The treatment also resulted in a significantly
      increased release of interleukin 6, but not of other cytokines. However, the
      biological response of hepatitis C virus-infected mononuclear cells to treatment
      with recombinant human granulocyte colony-stimulating factor was unrelated to any
      particular pattern of cytokine production.

PMID- 9162223
TI  - Constitutive secretion of GM-CSF by three different cell lines derived from a
      single patient with a progressive cutaneous lymphoproliferative disorder.
AB  - Three clonally related lymphoma lines (Mac-1, Mac-2A and Mac-2B) derived from
      progressive stages of CD30+ cutaneous T-cell lymphoma were found to
      constitutively secrete GM-CSF. The secretion of GM-CSF was identified by the
      ability of cell line supernatants to stimulate growth of megakaryoblastic cell
      line M-07e. This supernatant-mediated stimulation was inhibited by anti-GM-CSF
      MoAb (>98% inhibition for Mac-1 and Mac-2B lines, and >95% for Mac-2A line).
      Synthesis of GM-CSF was confirmed, at the mRNA level, by reverse transcriptase
      PCR and, at the protein level, by ELISA. Quantification of GM-CSF in supernatants
      by ELISA showed that the Mac-1 line, derived from an early, clinically indolent
      stage of the lymphoma, produced much more GM-CSF (>1600 pg/ml) than Mac-2A and
      Mac-2B lines which were derived from a late, aggressive stage (30-50 and 50-120
      pg/ml, respectively). Lack of inhibition of cell growth by anti-GM-CSF MoAb as
      well as lack of response to exogenous GM-CSF of cells cultured at low
      concentration have demonstrated that GM-CSF does not act directly as a growth
      factor for these lines. ELISA studies showed that GM-CSF concentration in serum
      and urine of the patient were not elevated (<5 pg/ml). From several other cell
      lines tested (two primary CD30+ ALCL, 2 CD30- non-lymphoblastic T-cell lymphomas
      and 4HD), only two HD lines with a T-lymphocyte phenotype secreted detectable
      amounts of GM-CSF. Our data show that cells lines from a patient with cutaneous T
      cell lymphoma constitutively secrete GM-CSF, although this capacity is relatively
      diminished in lines developed from more advanced disease.

PMID- 9162222
TI  - Granulocyte-macrophage colony-stimulating factor as adjuvant therapy for factor
      as adjuvant therapy for interferon alpha treatment of chronic hepatitis C.
AB  - The safety and efficacy of granulocyte-macrophage colony-stimulating factor (GM
      CSF) as adjuvant therapy for interferon alpha (IFN-alpha) treatment has been
      evaluated in 20 non-cirrhotic patients with chronic hepatitis C virus (HCV)
      infection. Adjuvant therapy with GM-CSF plus IFN-alpha was associated with less
      myelosuppression than with IFN-alpha alone (P < .01), although the rate of local
      adverse reactions increased. GM-CSF adjuvant therapy led to a 50% biochemical
      response (transaminase values within the normal range at therapy end) and to
      reductions in HCV RNA concentrations (median HCV RNA reduction of 99%, range 8
      100%), which were similarly observed in single IFN-alpha recipients (median HCV
      RNA reduction of 91%, range 38-100%). However, HCV RNA became undetectable in
      three biochemical responders to the GM-CSF adjuvant therapy, but in only one
      biochemical non-responder to IFN-alpha alone. The use of GM-CSF as adjuvant
      therapy is safe and, although it has not improved the biochemical response, it
      might potentiate the virologic response to IFN-alpha treatment alone.

PMID- 9162224
TI  - Tumour necrosis factor enhances the therapeutic effect of mitoxantrone in human
      ovarian cancer xenograft.
AB  - The combination of Tumour Necrosis Factor (TNF) and mitoxantrone was evaluated
      for potential chemotherapeutic effect against a human ovarian cancer cell line
      A2774 hetero-transplanted in female nude mice. Both antitumour efficacy (relative
      survival and reduction of ascites) and toxicity (weight loss and liver toxicity)
      of TNF alone, mitoxantrone alone or TNF + mitoxantrone were evaluated. A
      significant difference (P < 0.002) was observed only among animals bearing
      tumours treated with mitoxantrone (0.012 mg/Kg) + TNF (5 x 10(5) U/Kg) and
      controls. No cytotoxic effects were observed for this combination. These
      observations provide a rationale for further evaluation of TNF + mitoxantrone
      based regimes for the treatment of recurrent ovarian cancer.

PMID- 9162225
TI  - [Medico-biological definition of major clinical phenomena: syndrome, nosological
      form, disease].

PMID- 9162226
TI  - [Endogenous blocker of beta-adrenoreceptors].

PMID- 9162227
TI  - [Differences in blood supply of the brain and liver during acute blood loss in
      rats with different resistance to circulatory hypoxia].

PMID- 9162228
TI  - [Protein synthesis in neurons and satellite glial cells after global brain
      ischemia induced by heart arrest in rats].

PMID- 9162229
TI  - [Characteristic changes in the phospholipid composition of hepatocyte plasma
      membranes during hemorrhagic shock in cats].

PMID- 9162230
TI  - [Sensitivity of the respiratory system to oxygen during activation of brain
      GABAergic structures].

PMID- 9162231
TI  - [Effect of hydra peptide morphogen on the posthypoxic disorders in rat pups
      subjected to prenatal hypoxia].

PMID- 9162232
TI  - [Development of increased resistance of Ca-pump of the myocardial sarcoplasmic
      reticulum during adaptation to stress].

PMID- 9162233
TI  - [Cardioprotective effects of stimulation of peripheral mu-opiate receptors, and
      the role of opiatergic mechanisms in the pathogenesis of stress-induced heart
      damage].

PMID- 9162234
TI  - [Study of structural transitions in erythrocyte membranes during hereditary
      hemochromatosis].

PMID- 9162235
TI  - [Astaxanthine-induced inhibition of oxidation of apolipoprotein B-containing
      lipoproteins in human blood].

PMID- 9162236
TI  - [Changes in the levels of prostaglandin F 2alpha, leukotriene C4 and B4 in the
      rat blood after intravenous administration of radiocontrast media].

PMID- 9162237
TI  - [Reaction of the adrenal medulla to the effect of various extreme factors].

PMID- 9162238
TI  - [Effect of aceclidine on amnesia induced by scopolamine and electroshock in
      rats].

PMID- 9162239
TI  - [Effect of intravenous infusion of polyosm preparation on diuresis and indices of
      systemic and cerebral hemodynamics].

PMID- 9162240
TI  - [Postnatal stress enhances impairment of bilateral avoidance learning in mature
      rats with fetal alcohol syndrome].

PMID- 9162241
TI  - [Effect of befol on the threshold of electric fibrillation of heart ventricles].

PMID- 9162242
TI  - [Impairment of cellular and humoral immunity in rats with experimental depressive
      syndrome induced by systemic administration of 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)].

PMID- 9162243
TI  - [Changes in the spectrum of antibodies to membrane phospholipids in women with
      habitual abortion].

PMID- 9162244
TI  - [Changes in clinico-immunological indices of experimental allergic
      encephalomyelitis after treatment with perftoran].

PMID- 9162245
TI  - [Synthetic peptide--a fragment of beta-subunit of chorionic gonadotropin inhibits
      mitogen-stimulated proliferation of human lymphocytes in vitro].

PMID- 9162246
TI  - [Secretory reactions to somatoliberin and somatostatin of cultured cells of human
      pituitary adenomas producing growth hormone].

PMID- 9162247
TI  - [Sexual transmission of tick-borne encephalitis virus in laboratory mice].

PMID- 9162248
TI  - [Circadian rhythm of electrical potential of the epidermis in patients with
      hypertension].

PMID- 9162249
TI  - [Evaluation of the safety of focused ultrasound for noninvasive effect on the
      heart].

PMID- 9162250
TI  - [Quantitative characteristics of enterochromaffin cells in the pylorus during
      experimental duodenostasis].

PMID- 9162252
TI  - [Effect of fish liver oil on the rat testis].

PMID- 9162251
TI  - [Effect of extracorporeal helium-neon laser irradiation of the blood on morpho
      functional state of erythrocytes].

PMID- 9162253
TI  - [Manifestations of asymmetry during regeneration of microvessels of rabbit ears].

PMID- 9162254
TI  - [Serotonin-producing cells in the small intestine of hibernating animals during
      periods of hypothermia in the middle of winter and before spring awakening].

PMID- 9162255
TI  - [Mechanism of bacteriopyknosis].

PMID- 9162257
TI  - [The role of connective tissue matrix in thermomechanical reactions of the aorta
      wall].

PMID- 9162256
TI  - [Erythrocytes from the peripheral blood during direct mechanical heart massage].

PMID- 9162258
TI  - [Anatomic anomalies of P. Robin syndrome and therapeutic management].
AB  - The authors present their experience in the treatment of the Pierre Robin
      Syndrome in 32 cases. The purpose of this anatomical and clinical study is to
      guide and codify the surgical treatment of this malformation.

PMID- 9162259
TI  - The Vpreb1 and comt genes are closely linked and sublocalized to rat chromosome
      11q23.

PMID- 9162260
TI  - The gene for cytoplasmatic malate dehydrogenase, Mor2, is closely linked to the
      wobbler spinal muscular atrophy gene (wr).

PMID- 9162261
TI  - Regulation of adhesion and transendothelial migration of natural killer cells.
AB  - Under certain conditions, natural killer (NK) cells accumulate rapidly at
      extrahematic sites. In an effort to define the mechanisms underlying the
      recruitment of NK cells in tissues, we investigated their ability to adhere and
      transmigrate across endothelial cell (EC) monolayers. A considerable proportion
      of NK cells adhered to EC and about 30-40% of the adherent NK cells transmigrated
      across EC. NK cells were 2-3 times more efficient than resting T cells. Exposure
      of NK cells to IL-2 and IL-12 augmented their adhesive ability, while IL-4 had an
      inhibitory effect. mAb directed against CD18 and CD11a inhibited binding and
      migration of NK cells across resting or IL-1-activated EC, whereas anti-CD11b and
      Cd11c did not. Using IL-1-activated EC, it was found that anti-VLA-4 and anti
      VCAM-1 mAb utilized in concert with anti-CD18 significantly reduced adhesion and
      transmigration. The CS-1 peptide of fibronectin (which recognizes VLA-4), when
      used in concert with anti-CD18 and anti-VCAM-1 (but not anti-VLA-4), caused a
      small, but significant increase in inhibition. Thus, LFA-1 and VLA-4 are crucial
      determinants of the adhesive and migratory interaction with the vascular
      endothelium.

PMID- 9162262
TI  - Migratory functions of natural killer cells.
AB  - In numerous investigations it has been found that natural killer (NK) cells are
      among the cells arriving early at the site of defense. To reach the tissue sites
      of defense, the circulating NK cells have to penetrate through the capillary wall
      and actively migrate along the matrix proteins towards the tumor or infected
      target cells. For this process NK cells need adhesion receptors which do not
      anchor them but allow reversible binding. The migration capacity of NK cells is
      found to be higher than that of other lymphocytes. NK cells also have the ability
      to increase rapidly the migratory response. IL-2 and a peptide derived from ICAM
      2 are potential inducers of NK cell migration. ICAM-2 is expressed on
      endothelium, a site where lymphocytes start migration. Also, a matrix protein,
      fibronectin, increases NK cell migration. This review focuses on the migratory
      capacity of NK cells and on the receptors which NK cells use when they migrate on
      different substrata.

PMID- 9162264
TI  - Interaction of natural killer cells with extracellular matrix induces early
      intracellular signalling events and enhances cytotoxic functions.
AB  - NK cells are endowed with a wide array of adhesion molecules which mediate their
      interaction with endothelium and extracellular matrix components. We have shown
      that cross-linking of beta 1 integrins and CD44 on human NK cells induces a
      signal transduction pathway involving both tyrosine kinase activation and the
      modulation of intracellular calcium levels. Our studies have also demonstrated
      the ability of beta 1 integrins and CD44 to upregulate both the spontaneous and
      the CD16-triggered cytotoxic activity of human NK cells. Although the molecular
      mechanisms responsible for this costimulatory activity have not been defined yet,
      our studies indicate that the simultaneous cross-linking of beta 1 integrins and
      CD44 results in a synergistic effect on CD16-mediated enhancement of
      intracellular free calcium concentration, and suggest that this may be relevant
      for the cooperation observed.

PMID- 9162263
TI  - Expression and function of LFA-1 on A-NK and T-LAK cells: role in tumor target
      killing and migration into tumor tissue.
AB  - To study the role of the adhesion molecule lymphocyte function-associated antigen
      1 (LFA-1) in lymphokine-activated natural killer (A-NK) and mitogen-stimulated
      lymphokine-activated T killer (T-LAK) cell function, we evaluated the correlation
      between LFA-1 expression, as well as conjugate formation and cytotoxicity.
      Furthermore, the role of LFA-1 in the extravascular phase of migration of A-NK
      and T-LAK cells into B16 tumor tissue in vivo was studied. We demonstrate an 8
      fold increased LFA-1 expression on 4-day-old A-NK and T-LAK cells compared to
      unstimulated spleen cells. Moreover, we demonstrate that while LFA-1 expression
      on T-LAK cells was strictly correlated to conjugate formation and cytotoxic
      capacity, A-NK cells showed a less clear correlation between LFA-1 expression and
      these functions. Interestingly, anti-CD11a alone did not inhibit cytotoxicity,
      anti-CD18 alone did only inhibit cytotoxicity moderately (25%) whereas anti-CD11a
      and anti-CD18 in combination almost abrogated cytotoxicity against tumor targets
      P815 and YAC-1. Finally we demonstrate that pre-incubation of T-LAK cells with
      anti-bodies to CD11a and CD18 in combination inhibited their migration into the
      B16 tumors by more than 50-60%. In contrast, this pretreatment did not inhibit A
      NK cell migration. This difference could not be explained by differences between
      A-NK and T-LAK cells with respect to LFA-1 expression, turnover of antibody
      receptor complexes or complement-mediated lysis induced by the anti-LFA-1
      antibodies. We conclude that T-LAK cell binding to and lysis of tumor target
      cells and migration into the intercellular space of tumors depend strongly on the
      expression of LFA-1. In contrast, LFA-1 expression of A-NK cells showed a less
      clear correlation to these functions.

PMID- 9162265
TI  - Adhesion of activated natural killer cells to tumor necrosis factor-alpha-treated
      endothelium under physiological flow conditions.
AB  - Adhesion of activated natural killer (A-NK) cells to activated and nonactivated
      endothelial cells in vitro was studied under dynamic flow conditions. Endothelial
      cells grown on glass slides were either treated with tumor necrosis factor-alpha
      (TNF alpha) or medium, then placed into a flow chamber over which suspensions of
      A-NK cells were passed using a range of defined shear stress levels. Significant
      numbers of binding cells could be consistently observed at shear stress levels
      less than 3 dyn/cm2 on TNF alpha-activated endothelium or at 0.59 dyn/cm2 on
      nonactivated endothelium. Stable adhesion occurred rapidly following the initial
      interaction of the following cells with the endothelium in the absence of
      detectable rolling. Pretreatment of the A-NK cells with monoclonal antibodies
      directed against CD18 (LFA-1) or CD49d (VLA-4) resulted in a significant
      reduction in the number of binding cells. Simultaneous treatment with both
      monoclonal antibodies eliminated all A-NK adhesion occurring over 0.5 dyn/cm2.
      Pretreatment of the endothelial cells with antibodies against E- or P-selectin
      resulted in a small but significant reduction in binding only at 0.5 dyn/cm2. The
      binding efficiency of the A-NK cells was similar to that previously observed for
      T lymphocytes under the same conditions. Once bound, approximately half of the
      adherent cells could resist detachment when exposed to wall shear stresses over
      12 dyn/cm2. These findings indicate that A-NK cell adhesion to activated
      endothelium can occur under shear stress conditions which are representative of
      postcapillary venules and that this binding is mediated principally by both CD18
      and CD49d. A-NK cell adhesion also occurs to nonactivated endothelium but only at
      wall shear stress levels less than 1 dyn/cm2.

PMID- 9162267
TI  - Infiltration and lysis of tumour cell aggregates by adherent interleukin-2
      activated natural killer cells is distinct from specific cytolysis.
AB  - Adoptively transferred activated natural killer (A-NK) cells infiltrate tumours
      in vivo. Two in vitro B16-F10 melanoma tumour models were used to study with
      fluorescence and electron microscopy the infiltration of adherent interleukin 2
      (IL-2) A-NK cells: (1) substratum-bound sessile microtumours (MTs), and (2) three
      dimensional cell growth on macroporous gelatinous microcarriers (Cultispheres).
      From 2 h and on increasing numbers of A-NK cells infiltrated the MTs regularly
      surrounded by a widened intercellular space. An IL-2-dependent disintegration of
      MTs began at 6-8 h resulting in a release of vital and dead cells. A-NK cell
      invasion into Cultispheres effectively displaced the melanoma cells from the
      highly convoluted substratum. Thus, A-NK cell infiltration had a protease-like
      effect on the tumour cell aggregates which might have a bearing on the
      interpretation of their cytolytic effect on target cells. Ultrastructural
      evidence was not obtained of specific A-NK/target conjugate formation or of
      granule-mediated target cell destruction in either model tumour.

PMID- 9162266
TI  - Morphological studies of effector cell-microvessel interactions in adoptive
      immunotherapy in tumor-bearing animals.
AB  - Murine lymphokine-activated natural killer (A-NK) cells are able to migrate to
      and accumulate in tumor metastases. However, the exact migratory pattern is as
      yet unknown. In the present study, we have investigated the migration from the
      vasculature towards malignant tissues of various effector cells. Our results
      indicate that murine A-NK cells seem to be arrested for an extended period of
      time in the microvasculature and also, although infrequently, to adhere to the
      endothelial lining of larger vessels close to tumor tissues before extravasation.
      While murine T lymphokine-activated killer and rat A-NK cells accumulate
      significantly in the subendothelial areas of larger venules in normal tissues, no
      such accumulation is observed with respect to murine A-NK cells. Electron
      microscopy reveals that the murine A-NK cells undergo an extreme deformation
      during extravasation and tumor infiltration. Furthermore, the cells are shown to
      be in an activated stage probably facilitating their migration, and hence, the
      elimination of tumor cells.

PMID- 9162268
TI  - Ultrastructure of interactions between activated murine natural killer cells and
      melanoma cells in an extracellular matrix (Matrigel) environment.
AB  - Mixed suspensions of B16-F10 melanoma cells and murine interleukin 2 (IL2)
      activated (adherent) natural killer (A-NK) cells cultured for 5 days were
      enclosed in gelled droplets of reconstituted basement membrane extracellular
      matrix (Matrigel). After incubation under cell culture conditions +/- IL2,
      samples were fixed for electron microscopy after 10 min and 2, 6, and 24 h. At
      the first time point cells were rounded and randomly distributed in the gel, at 2
      h A-NK cells migrated vividly and formed contacts with target cells. At 6 h there
      were extensive effector:target conjugates and melanoma cell debris in the gel.
      Directed exocytosis of A-NK cell-specific granules could not be verified. At 24 h
      very few intact B16 cells remained in IL2-substituted specimens and there were
      large amounts of lytic melanoma cell remnants; in the absence of IL2 substantial
      numbers of surviving melanoma cells formed aggregates. At this time some A-NK
      cells had ingested melanoma cell components which probably fused with specific
      two-compartment granules to form large phagolysosomes. A-NK cells enlarged into a
      giant cell type with huge cytoplasmic accumulations of amorphous material
      described as mucoid masses by others.

PMID- 9162270
TI  - The rationing debate. Rationing within the NHS should be explicit. The case
      against.

PMID- 9162271
TI  - [The effect of calcium channel blockers on anxiety evoked by amputation of the
      vibrissae in rats].
AB  - The effect of diazepam (0.5 mg/kg) and calcium channel blockers on the behavior
      of rats in an "open field" was studied on a model of incomplete amputation of
      vibrissae. Diazepam, diltiazem (1 mg/kg), fendiline (1 mg/kg), and cinnarizine (1
      mg/kg) stimulated motor activity of animals with amputated vibrissae. Nifedipine
      (0.5-5 mg/kg) and verapamil (0.5-5 mg/kg) were practically inactive in these
      tests. It is concluded that diltiazem, fendiline, and cinnarizine possess
      anxiolytic activity in this model. On the basis of the results obtained, the
      methods for studying the anxiolytic activity on animals are discussed.

PMID- 9162269
TI  - Informed consent: the intricacies.

PMID- 9162272
TI  - [The effect of hydrocortisone on a neurogenic pain syndrome in rats].
AB  - The effect of hydrocortisone on the neurogenic pain syndrome induced by damage to
      the peripheral nerves was studied in 40 male Wistar rats. Intraperitoneal
      administration of 10 mg/kg of the drug caused both hyperalgesia and hypoalgesia.
      The direction of the hydrocortisone effect on the neurogenic pain syndrome
      depended on the time of administration: chronic administration before the damage
      to the nerves promoted the development and intensity of the syndrome; treatment
      applied after the nerve damage delayed the development of the syndrome. It is
      suggested that the mechanism of the hydrocortisone effect on the neurogenic pain
      syndrome may be realized via the central link through the effect of the hormone
      on the glucocorticoid receptors of the brain structures.

PMID- 9162273
TI  - [The role of the muscarinic receptors in the pathogenesis of the convulsive state
      induced by korazol in rats].
AB  - It was established in experiments on albino rats that blockade of the muscarinic
      receptors by various M-cholinolytics reduces the dose of corazol necessary for
      the development of a convulsive state. Preliminary administration of some
      cholinopositive agents raises the corazol action threshold. It is suggested on
      the basis of pharmacological analysis that the role of the cholinergic system in
      the pathogenesis of corasol-induced convulsive state in rats is mediated by the
      function of cholinoreceptors related to subtype M4 or M1.

PMID- 9162274
TI  - [The effect of ritanserin on the formation and expression of an opiate abstinence
      syndrome].
AB  - The described dependence was formed in mice [correction of rats] by subcutaneous
      injections of morphine in doses growing from 10 to 100 mg/kg (8 days, twice a
      day). The effect of 5-HT2 receptor blocker ritanserine (1, 5, and 10 mg/kg) on
      expression of the abstinence syndrome (according to the behavioral and somato
      autonomic parameters) 24 h after morphine discontinuation was studied.
      Ritanserine attenuated the manifestation of some abstinence parameters associated
      with activation of the serotonin system in formation of the dependence. The
      effect was less in expression of abstinence.

PMID- 9162275
TI  - [The antinociceptive effect of tramal when combined with nonsteroidal anti
      inflammatory preparations].
AB  - The antinociceptive effect of tramal and its combinations with nonsteroidal anti
      inflammatory drugs (ortophen, indomethacin, naproxen, acetylsalicylic acid, and
      ibuprofen) was studied in 110 male albino rats on models of electric and thermal
      stimulation. Possessing their own antinociceptive activity, nonsteroidal anti
      inflammatory drugs potentiated the analogous effect of tramal. In vitro tramal
      was intensively demethylated by the rat liver microsomal fraction. In therapeutic
      concentrations ortophen and naproxen suppressed the rate of tramal demethylation
      by the rat microsomes. The potentiating effect of nonsteroidal anti-inflammatory
      drugs in relation to tramal is apparently connected with the delay in its
      biotransformation and conversion to inactive metabolites.

PMID- 9162276
TI  - [The inhibition of synaptic acetylcholinesterase by postsynaptic muscle
      relaxants].
AB  - In experiments on narcotized cats records of contractions of the anterior tibial
      muscle in response to indirect stimulation showed that the mean dose of
      acetylcholine (Ach) blocking neuromuscular conduction and that of carbachole
      (Cch) for their injection into the corresponding femoral artery was 18.9 and 0.16
      mumole/kg, respectively. In the period of partial blockade induced by
      depolarizing myorelaxants, the blocking dose of Ach reduced to a greater measure
      than that of Cch. Most nondepolarizing myorelaxants used in the experiment
      increased the blocking Ach dose less than the Cch dose. Benzoquinone possessing
      the highest antiacetylcholinesterase activity in vitro even reduced the blocking
      dose of Ach. This difference is apparently due to inhibition of the activity of
      synaptic acetylcholinesterase by the muscle relaxants.

PMID- 9162277
TI  - [Changes in the blood circulation in the middle cerebral and common carotid
      arteries of rats under the influence of flunarizine].
AB  - Experiments conducted on Wistar rats under general anesthesia using the Doppler
      ultrasonic method showed that flunarizine caused a slowly developing (for 20
      min), moderate (25%), and prolonged (90 min) increase of the blood flow in the
      middle cerebral artery. In the common carotid artery the drug induced two-phase
      changes in blood circulation. The initial increase in the blood flow was replaced
      by its reduction below the basic level.

PMID- 9162278
TI  - [The effect of lithium chloride on the desynchronization of "reserpine-induced
      depression"].
AB  - Lithium chloride (5 mg/kg i.m. for 10 days in the morning but not in the evening)
      prevented effectively desynchronization of "reserpine depression" in mice and
      rats: the spectra and structure of the rhythms of behavioral parameters (open
      field), body temperature, content of serotonin and its metabolites in the brain
      and that of glucocorticoids in blood plasma were almost the same as those in
      intact animals; the circadian harmony of all parameters were correlated in the
      best manner and their mean circadian values were restored.

PMID- 9162279
TI  - [The effect of fructose-1,6-diphosphate, cytochrome c and their combination on
      the size of the necrotic area in transient myocardial ischemia].
AB  - The effect of fructose-1, 6-diphosphate (200 mg/kg), cytochrome C (20 mg/kg) and
      their combinations on the size of the zone of necrosis 4 and 72 h after 15-min
      transitory myocardial ischemia was studied. Combination of the compounds under
      study inhibited considerably the development of post-occlusion and reperfusion
      arrhythmias and reduced the size of necrosis 4 h after their administration as
      prophylactic and arresting measures (to 23.8 +/- 2.9 and 29.3 +/- 3.6% of the
      ischemic zone, respectively, in 42.8 +/- 3.8% in the control). A combined course
      of cytochrome C and fructose diphosphate also limited the size of the necrotic
      zone 72 h after transitory ischemia. Separate single administration of fructose
      diphosphate and cytochrome C caused no essential changes in the size of
      myocardial necrosis recorded 72 h after transitory myocardial ischemia.

PMID- 9162280
TI  - [The mechanism of the anti-arrhythmia action of mu-opioid-receptor agonists in a
      model of CaCl2-induced arrhythmias: the role of the autonomic nervous system].
AB  - It was established that selective ligands of the mu-opioid receptors DAGO and
      DALDA exhibit antiarrhythmic activity on a model of CACl2-induced arrhythmias
      when infused intravenously in a dose of 0.2 mg/kg. The autonomic nervous system
      does not take part in realization of the antiarrhythmic effect of DAGO and DALDA.
      It is supposed that this effect of DAGO and DALDA is associated with activation
      of cardiac mu-opioid receptors.

PMID- 9162281
TI  - [The participation of the mu-, delta- and kappa-opioid receptors in the
      realization of the anti-arrhythmia effect of Rhodiola rosea].
AB  - A course of the adaptogen extractum Rhodiola rosea (3.5 ml/kg given per os daily
      for 8 days). produces am antiarrhythmic effect on models of epinephrine-induced
      arrhythmia. Blockade of mu-opiate receptors (OR) by naloxone (0.2 mg/kg) and
      delta-OR by ICI 174.864 (2.5 mg/kg) had no effect on the resistance of the heart
      of rats adapted to epinephrine. Higher doses of naloxone reduced significantly
      the antiarrhythmic effect of extr. Rhodiola. The antiarrhythmic effect of the
      extract is assumed to be related to activation of the opioid system and
      stimulation of kappa-OR.

PMID- 9162282
TI  - [The role of the natriuretic hormone in the action of nifedipine and verapamil on
      the kidneys].
AB  - It was demonstrated in experiments on albino rats that under the effect of
      nifedipine and verapamil the increase in the excretion of electrolytes and water
      by the kidneys is accompanied with a rise in the natriuretic hormone (NUH)
      content in blood plasma and urine. This causes the renal effects of the drugs
      under study. The sensitivity of the kidneys to NUH increases in this case.

PMID- 9162283
TI  - [The anticoagulant activity of fucoidans].
AB  - The influence of the degree of fucoidan macromolecules sulfation on their ability
      to induce an anticoagulant effect was studied. In in vitro experiments with the
      basic stain and in in vivo experiments on rabbits with performance of Quick's
      test, APTT, and spectrophotometric determination of antithrombin III (AT-III)
      activity a direct dependence of the intensity and duration of the anticoagulant
      effect on the degree of fucoidan sulfation was shown. The degree of sulfation was
      increased by alkaline treatment and anion-exchange chromatography of the
      compound. The anticoagulant effect of the fucoidan fractions under study was
      realized practically without affecting AT-III activity. And this direct effect of
      inhibition of the coagulation factors could be immediately arrested by
      intravenous injection of a neutralizing dose of the heparin antagonist VIM-DEMA.

PMID- 9162284
TI  - [The effect of 2-methyl-4-amino-6-hydroxypyrimidine on delayed hypersensitivity].
AB  - The effect of the immunomodulator 2-methyl-4-amino-6-oxypyrimidine (MAOP)on
      delayed hypersensitivity was studied in experiments on mongrel mice and in C57Bl
      and CBA mice. The effect of MAOP and that of oxymethyluracil on delayed
      hypersensitivity to sheep erythrocytes and dinitrofluorobenzene were compared.
      Immunosuppression of mice was induced by hydrocortisone in a dose of 50 mg/kg.

PMID- 9162285
TI  - [The effect of acetylcysteine and dipyroxime on the immune reactions in acute
      dichloroethane poisoning].
AB  - It was established in experiments on CBA mice and outbred rats that acute
      dichloroethane (0.75 LD50) intoxication leads to decrease of antiinfectious
      immunological and nonspecific resistance of the organism, antibody production,
      and cell immune response evaluated according to the delayed-type hypersensitivity
      (DTH) reaction. Administration of the antidote acetyl-cysteine increased
      suppression of the reactions under study (with the exception of DTH), while
      dipiroxim weakened it. The dipiroxim effects are associated with reactivation of
      immunocyte alpha-naphthyl-AS-acetatesterase by this compound (and possibly also
      of other types of esterases of immunocompetent cells).

PMID- 9162286
TI  - [The immunobiological properties of trimezon and levamisole on models of humoral
      and cell-mediated immunogenesis].
AB  - It was shown in mice experiments that intragastric administration of the low
      molecular synthetic immunomodulator of the 8-azasteroid series trimesone
      increases the immune response of humoral and cell-mediated types to the thymus
      dependent antigen, the sheep erythrocytes. The stimulating effect of the drug in
      vivo is determined by the dose, the antigen load, and the animals' genotype and
      does not yield to the effect of levamisole or exceeds it in identical
      experimental conditions.

PMID- 9162287
TI  - [The mechanism of histamine liberation from rat mast cells under the action of x
      ray contrast media].
AB  - It was demonstrated in rat experiments that a positive direct correlation exists
      between the decrease in the amount of histamine in rat peritoneal must cells
      after intravenous infusion of radiopaque agents (ROA) in a dose of 2 ml/kg and
      the amount of these penetrating from the blood into the peritoneal cavity. The
      degree of penetration is determined by the chemical structure and/or
      physiochemical properties of the ROA.

PMID- 9162288
TI  - [The neuroprotective effect of GABA-ergic substances in cerebral ischemia].
AB  - The GABA precursor progabide, the GABA-aminotransferase inhibitor valproate, and
      the GABA receptor agonist baclofen increased the resistance of mice and rats to
      ischemia of the brain in two different modes. Both time and dose curves of the
      neuroprotective and hypothermal effects correlated in individual animals within a
      group, but there was no correlation for different series. Probably hypothermia is
      just one of the components in the mechanism of the neuroprotective effect of
      GABAergic compounds.

PMID- 9162289
TI  - [The effect of substances with nootropic activity on oxidative phosphorylation in
      brain mitochondria in acute craniocerebral trauma].
AB  - An open craniocerebral trauma was simulated in rat experiments. Oxidative
      phosphorylation in the brain mitochondria was studied by polygraphy 24 h after
      the trauma. It was found that trauma to the brain leads to inhibition of
      respiration in mitochondria in various metabolic states. Nooglutil in a dose of
      50 mg/kg prevents these changes. Nooglutil is more effective than picamilon (500
      mg/kg) and piriditol (100 mg/kg).

PMID- 9162290
TI  - [A biochemiluminescent analysis of the pharmacotherapeutic activity of
      acetylsalicylic acid in combination with quercetin in a hypoxic syndrome].
AB  - The effect of acetylsalicylic acid in combination with quercetin on blood serum
      biochemiluminescence in the hypoxic syndrome was studied. Possessing marked
      antioxidant activity, this drug combination prevented changes in the kinetics of
      blood serum luminescence in all periods of the investigation.

PMID- 9162291
TI  - [The effect of ximedon on adaptation to prolonged immobilization stress].
AB  - It was shown in rabbit experiments that the use of ximedon in long-term
      immobilization stress limits activation of lipid peroxidation, stimulates the
      main enzymes of the antioxidant systems, causes of hypolipidemic, preventive
      endotheliotropic, and cardiotropic effect.

PMID- 9162293
TI  - [The comparative effect of melatonin and diazepam on shifts in the anxiety-phobia
      status of rats evoked by damage to the amygdala].
AB  - Disorders develop in the emotional sphere in the form of increased anxiety and
      fear in amygdalectomized rats. The pineal hormone melatonin and diazepam (in an
      equal dose of 0.1 mg/kg) alleviate the state of anxiety and fear in the animals.
      Despite some differences in behavioral activity, the effect of the drugs appears
      to be similar. This suggests that melatonin possesses anxiolytic properties which
      may be related to its effect on the function of the limbic structures.

PMID- 9162292
TI  - [The enhancement of human thermal resistance by the single use of bemitil and
      fenibut].
AB  - The authors studied the effect of single intake of bymetil (0.5 g) and phenibut
      (0.25 g) on the thermal state, gas-energy exchange, blood oxygenation, working
      capacity, and the subjective status of man in intensive physical exertion in
      isolating means of individual protection. The drugs under study increased thermal
      resistance, promoted normal supply of the organism with oxygen, and provided the
      maintenance of man's high working capacity under conditions which lead to his
      overheating. The best protective effects was produced in this case with phenibut.

PMID- 9162294
TI  - [An evaluation of the immunotropic and hemopoietic effects of hyperbaric
      oxygenation as an experimental pathological model].
AB  - Apoptosis, programmed cell death, being a physiological process is manifested by
      degenerative changes of the cell structures. Augmentation of apoptosis or
      distributed receptor-signal interaction of the cells may be caused by the toxic
      products of radiolysis and cancerogenesis. Hyperbaric oxygenation (HBO) was used
      as a model resembling apoptosis. The parameter of the humoral immune response to
      different HBO regimens and correction of immunodepression by a carotene
      tocopherol complex (CTC) were compared. The next stage in the study of the CTC
      antioxidant effect in gamma-radiation was determination of the extent of
      endogenous colony formation under the influence of different HBO regimens. A
      moderate immunodepressive effect of HBO was noted. Combination of CTC and HBO in
      small regimens induced a moderate immunostimulating and hemopoietic response. The
      suggested pathological model may be used in study of antioxidants. CTC showed
      hemopoietic and immunocorrective action.

PMID- 9162295
TI  - [The effect of n-3 polyunsaturated fatty acids on the blood coagulation system].
AB  - The article presents the epidemiologic data on the antithrombotic and
      antiatherosclerotic effect of n-3 polyunsaturated fatty acids, and the current
      information on the mechanism of the effect of these compounds on the system of
      blood coagulation.

PMID- 9162296
TI  - Ovarian cancer incidence and mortality in American Indian, Hispanic, and non
      Hispanic white women in New Mexico.
AB  - Although ethnic and racial differences in ovarian cancer incidence and mortality
      have been reported worldwide, few published data have addressed the epidemiology
      of ovarian cancer among U.S. American Indians and Hispanics. We reviewed ovarian
      cancer incidence and survival data from New Mexico's population-based cancer
      registry collected from 1969 to 1992, and examined state vital records data for
      ovarian cancer deaths collected from 1958 to 1992, focusing on ethnic differences
      in occurrence and outcomes of ovarian malignancies. Non-Hispanic white women had
      age-adjusted incidence rates that were slightly higher (13.3/100,000) than rates
      for American Indians (11.4) and Hispanics (10.7) over the 24-year period. Ovarian
      cancer mortality rates were also higher for non-Hispanic whites than for minority
      women. Neither incidence rates nor mortality rates for ovarian cancer improved
      over the span of the study period. In addition, the stage at diagnosis did not
      shift substantially over time for any of the ethnic groups studied, nor did the
      distribution of various histopathological types shift proportionately. Only
      slight improvement was observed in 5-year survival over the time period of the
      study, with greater gains among younger (50 years old or less) versus older
      women. Ethnic differences in ovarian cancer incidence and mortality were apparent
      in our population-based data. However, our analysis indicated no reduction in
      ovarian cancer incidence or mortality in our state over the past quarter century
      and only slight improvement in 5-year survival.

PMID- 9162297
TI  - The presence of human papillomavirus-16/-18 E6, p53, and Bcl-2 protein in
      cervicovaginal smears from patients with invasive cervical cancer.
AB  - Cervical cancer is the second leading cause of death from cancer in women
      worldwide, and recent epidemiological studies have strongly implicated the
      sexually transmitted human papillomavirus (HPV) as a causative agent. The ability
      of high-risk HPVs to contribute to malignant progression seems to depend on
      expression of the viral E6 and E7 oncogenes. The E6 oncoprotein forms a complex
      with the cellular tumor suppressor protein p53, leading to degradation of p53 via
      ubiquitin-dependent proteolysis. Thus, E6 expression results in the loss of p53
      function in cells, including stimulation of apoptosis and inhibition of the
      expression of the antiapoptotic protein bcl-2. Recently, we found increased bcl-2
      expression in cervical carcinoma cell lines containing mutated or E6-inactivated
      p53 (X. L. Liang, S. Mungal, A. Ayscue, J. D. Meissner, P. Wodnicki, G. Gordon,
      S. Lockett, and B. Herman. J. Cell. Biochem., 57: 509-520, 1995). Based on these
      findings, we examined Papanicolaou smears from 94 women with varying degrees of
      cervical disease for the presence or absence of p53, HPV-16/18 E6, and bcl-2
      proteins using immunofluorescence microscopy. Our findings indicate that there is
      a statistically significant, inverse association between the presence of p53 and
      invasive cervical disease [odds ratio (OR), 0.3; 95% confidence interval (CI),
      0.1-0.7]. Moreover, the odds of being diagnosed with an invasive stage of
      cervical cancer were 3.7 times higher (95% CI, 1.6-8.8) for women positive for
      the E6 protein and 17 times higher (95% CI, 5.5-58.3) for women positive for the
      bcl-2 protein compared with women negative for E6 and bcl-2. Women with invasive
      cervical cancer were also 4.59 times more likely to test positive for the
      presence of more than one marker (95% CI, 1.8-11.8). Chi(2) analysis demonstrated
      a strong association between the presence of E6 and bcl-2 (P < 0.001) as well as
      between the presence of E6 of bcl-2 and diagnosis (P = 0.015 and < 0.001,
      respectively). In the multivariate analysis, the presence of bcl-2 (OR, 18.8; 95%
      CI, 5.5-67.8) and age at diagnosis (> or = 50 years; OR, 7.8; 95% CI, 2.5-24.5)
      showed significant association with Invasive cervical disease. These findings
      indicate that: (a) the presence of the bcl-2 protein is strongly associated with
      the development of invasive cervical disease: (b) the pattern of the presence of
      high-risk HPV-E6, p53, and bcl-2 proteins may be useful for identifying women at
      increased risk for the development of invasive cervical cancer; and (c) a defect
      in apoptosis may partially underlie the development of cervical cancer.

PMID- 9162298
TI  - Glutathione-S-Transferase M1 and codon 72 p53 polymorphisms in a northwestern
      Mediterranean population and their relation to lung cancer susceptibility.
AB  - Several polymorphic genes have been reported to be possibly involved in modifying
      lung cancer risk in smokers. The gene GSTM1 is frequently deleted in human
      populations, and the null genotype has been reported to be a risk factor for
      developing lung carcinoma. A germline polymorphism of p53 with a single-base
      change at codon 72 that causes an amino acid replacement of arginine (Arg; CGC)
      by proline (PRO; CCC) has also been reported to be associated with cancer
      susceptibility in a Japanese population. Both polymorphisms were genotyped by PCR
      in a northwestern Mediterranean healthy population (n = 147) and in a group of
      lung cancer patients (n = 139). The results showed that the frequency of the
      GSTM1 null genotype was higher in the lung cancer patients compared to the
      controls [odds ratio (OR), 1.57; 95% confidence interval (CI), 0.99-2.51]. The
      histological subtypes most clearly modified were small cell carcinoma (OR, 1.89;
      CI, 0.97-3.65) and adenocarcinoma (OR, 1.93; CI, 0.90-4.14). The null GSTM1
      genotype was more frequent among those cancer patients who were medium/ light
      smokers (< or = 50 pack-years) and in those who showed an onset of the disease at
      a more advanced age. The study of the p53 polymorphism in the healthy population
      showed allele frequencies of 0.79 (Arg) and 0.21 (Pro). The frequencies found in
      the lung cancer patients were statistically similar. Both polymorphisms were
      studied together, and the relative risk of the combination null GSTM1 and Pro/Pro
      or Arg/Pro genotypes was calculated taking the combination of GTSM1 + together
      with Arq/Arg as a baseline. The OR found (1.97; CI, 1.03-3.73) suggests that the
      Pro allele of the p53 germline polymorphism may slightly increase the risk fo the
      GSTM1 null genotype among smokers.

PMID- 9162300
TI  - Reproducibility of the measurement of colonic proliferation using
      bromodeoxyuridine across laboratories.
AB  - Although measures of colonic cell proliferation are being used as potential
      intermediate markers in chemoprevention studies, measurement standardization is
      still ongoing. This study was designed to assess the reproducibility of the
      labeling index quantification, as measured by bromodeoxyuridine, across four
      laboratories experienced in its use. Each institution submitted 10 slides, with
      one circled area of each slide to be scored. Each site followed its standard
      procedures for scoring colonic crypts; no attempts to standardize these
      procedures were made. There was high concordance among the laboratories on
      whether scorable crypts were present on a particular slide, but only two pairs of
      laboratories demonstrated agreement statistically greater than that predicted by
      chance. The overall difference among the sites on the number of scorable crypts
      was marginally significant (P = 0.083), and there was a highly significant
      overall difference in the magnitude of the labeling index (P < 0.0001). Sites 1
      and 2 tended to have similar results, as did sites 3 and 4, most likely due to
      common training. Even with these discrepancies, high correlation (r > 0.75) was
      observed among the reported labeling index values for each pair of laboratories.
      Without standardized training, these laboratories may differ in the crypts
      considered appropriate for counting and in whether cells are counted as labeled
      or unlabeled. These results suggest that standardized training in scoring across
      all sites performing labeling index determinations is required to assure
      reproducibility across sites or studies. These results may also help explain
      discrepancies in the average values of the labeling index reported in the
      literature.

PMID- 9162299
TI  - Evaluation of proliferating cell nuclear antigen as a surrogate end point
      biomarker in actinic keratosis and adjacent, normal-appearing, and non-sun
      exposed human skin samples.
AB  - The incidence of nonmelanoma skin cancer, including both squamous cell carcinoma
      and basal cell carcinoma, is a significant health problem in the United States.
      Actinic keratosis (AK), the precursor of cutaneous squamous cell carcinoma, is a
      major risk factor for nonmelanoma skin cancer. In addition, AKs are tissue
      targets for the identification of biomarkers for use in chemopreventive studies.
      The biomarker addressed in this study is epidermal cell proliferation, as
      quantitated by proliferating cell nuclear antigen (PCNA). Shave biopsies were
      obtained from AKs, tissue immediately adjacent to AKs, normal-appearing, upper
      medial arm skin, and non-sun-exposed skin from 19 subjects. When any degree of
      PCNA staining was considered positive (semiquantitative 1-4 scale), there was a
      significant difference and a progressively increasing mean PCNA labeling index
      (LI) in the total epidermis (basal and suprabasal layers), beginning with non-sun
      exposed buttock skin, with the lowest LI (2.5 + or - 1.6%), followed by upper
      medial arm skin (12.3 + or - 7.4%; P = 0.0015), skin adjacent to AKs (19.2 + or -
      12.2%; P = 0.0218), and finally, AKs with the highest LI (34.6 + or - 20.1%; P =
      0.0017). This same pattern was observed when the epidermis was separated into
      basal and suprabasal layers, with the exception of a nonsignificant result for
      upper-medial arm skin compared with adjacent skin in the basal layer (P =
      0.3981). PCNA LIs were also analyzed separately by staining intensity (i.e.,
      scores of 1-4). The PCNA LI in skin with varying degrees of sun damage and/or
      histological atypia is a candidate surrogate end point biomarker for skin cancer
      chemoprevention studies.

PMID- 9162301
TI  - Aberrant crypts as a biomarker for colon cancer: evaluation of potential
      chemopreventive agents in the rat.
AB  - We assessed the effects of 41 potential chemopreventive agents in the F344 rat
      using the inhibition of carcinogen-induced aberrant crypt foci (ACF) in the colon
      as the measure of efficacy. ACF were induced by the carcinogen azoxymethane in
      F344 rats by two sequential weekly injections at a dose of 15 mg/kg. Two weeks
      after the last azoxymethane injection, animals were evaluated for the number of
      aberrant crypts detected in methylene blue-stained whole mounts of rat colon. The
      41 agents were derived from a priority listing that was based on reports of
      chemopreventive activity in the literature and/or efficacy data from in vitro
      models of carcinogenesis. The list of agents included representative examples of
      phytochemicals, vitamins, minerals, inhibitors of proliferation, inducers of
      Phase 1 and Phase 2 metabolism systems, nonsteroidal anti-inflammatory agents,
      and differentiation agents. Eighteen agents were positive in the assay,
      significantly reducing the incidence of ACF at least in one of two doses tested.
      As a chemical class, the nonsteroidal anti-inflammatory drugs, which included
      ibuprofen, ketoprofen, piroxicam, and indomethacin, were most active; other less
      potent agents were arginine, butylated hydroxyanisole, curcumin, diallyl sulfide,
      difluoromethylornithine, 18 beta-glycyrrhetinic acid, indole-3-carbinol,
      oltipraz, purpurin, rutin, and the sodium salts of butyrate, selenite, and
      thiosulfate. Twenty-three agents did not inhibit ACF; included among these were
      several agents that promoted the development of ACF at one or both doses tested:
      benzyl isothiocyanate,calcium glucarate, catechin, dihydroepiandosterone,
      fluocinolone acetonide,folic acid, levamisole, 2-mercaptoethanesulfonic acid,
      nordihydroguiaretic acid, potassium glucarate, propyl gallate, beta-sitosterol,
      sodium cromolyn, sodium molybdate, and sulfasalazine. The aberrant crypt assay
      demonstrates reasonable specificity and sensitivity in predicting which agents
      are likely to prevent colon cancer.

PMID- 9162302
TI  - (32)P-postlabeling detection of DNA adducts in peripheral white blood cells of
      greenhouse floriculturists from western Liguria, Italy.
AB  - Pesticides are widely used in agriculture to enhance crop yields and to control
      disease vectors. Floriculturists work frequently in greenhouses and may be
      exposed to high levels of pesticides, which may result in adverse health effects.
      To evaluate the relationship between exposure to pesticides and DNA adduct
      formation in peripheral WBCs of Italian floriculturists, the nuclease P1
      modification of a (32)P-postlabeling assay was used to analyze WBC DNA from
      floriculturists (n = 26) and matched controls (n = 22). DNA adduct-positive
      samples were more frequent in floriculturists (11/26; 42%) than in matched
      controls (2/22; 9%) (P < 0.01). Slightly higher frequencies of DNA adduct
      positive samples were observed in floriculturists > or = 44 years of age (53%)
      and in female floriculturists (57%). Floricultural practice was found to be
      associated with a significantly higher DNA adduct-positive rate in WBCs (rate
      ratio, 5.12; 95% confidence interval, 1.1-23.7) after allowing for the effects of
      age and gender. These two latter covariates were not significantly associated
      with DNA adduct-positive rates. The quantitative levels of DNA adducts were
      significantly higher in floriculturists than in matched controls according to the
      Mann-Whitney nonparametric statistic (P = 0.0052). The median adduct level for
      positive samples among floriculturists was 1.5/10(8) bases. A specific, well
      visible spot, named alpha adduct, was detected in 7 out of the 11 DNA adduct
      positive samples from floriculturists but in none of the (22 + 20) referent
      samples (P = 0.0004). The presence of pesticide-related DNA adducts was confirmed
      clearly using the butanol extraction procedure. Six of 8 floriculturists and 0 of
      10 referents were found positive with this method. The median adduct level for
      positive samples was 6.0/10(8) bases. Two strong spots close to the origin could
      be identified in all six positive floriculturists, using the butanol extraction
      procedure. No association between DNA adducts and use of specific pesticides was
      observed.

PMID- 9162303
TI  - Toxicity evaluation of difluoromethylornithine: doses for chemoprevention trials.
AB  - This intergroup trial was developed to determine the toxicity of relatively low
      doses of difluoromethylornithine (DFMO) administered to humans for 1 year. The
      goal was to find an appropriate DFMO dose for use in human chemoprevention
      trials. Patients with resected superficial bladder cancers were studied.
      Following stratification, they were randomized to daily DFMO doses of 0.125,
      0.25, 0.5, or 1.0 g/day for a planned period of 1 year. Patients were followed
      closely for evidence of drug toxicity. Seventy-six patients were evenly
      randomized (19 per group) to receive each dose of DFMO. Forty-nine patients
      received DFMO for more than 200 days while 35 received the drug for > or = 350
      days. No substantial drug-related toxicity was observed at any dose. DFMO doses
      of > or = 1 g/day for periods up to 1 year appear to be without significant
      toxicity in most patients. This dose range may be appropriate for use in future
      human cancer chemoprevention trials.

PMID- 9162304
TI  - The polyp prevention trial I: rationale, design, recruitment, and baseline
      participant characteristics.
AB  - The Polyp Prevention Trial (PPT) is a multicenter randomized controlled trial
      examining the effect of a low-fat (20% of total energy intake), high-fiber (18
      g/1000 kcal), high-vegetable and -fruit (5-8 daily servings) dietary pattern on
      the recurrence of adenomatous polyps of the large bowel, precursors of most
      colorectal malignancies. Eligibility criteria include one or more adenomas
      removed within 6 months of randomization; complete nonsurgical polyp removal and
      complete colonic examination to the cecum at the qualifying colonoscopy: age 35
      years of more; no history of colorectal cancer, inflammatory bowel disease, or
      large bowel resection; and satisfactory completion of a food frequency
      questionnaire and 4-day food record. Of approximately 38,277 potential
      participants with one or more polyps recently resected, investigators at eight
      clinical centers randomized 2,079 (5.4%; 1,037 in the intervention and 1,042 in
      the control arm) between June 1991 and January 1994, making the PPT the largest
      adenoma recurrence trial ever conducted. Of PPT participants, 35% are women and
      10% are minorities. At study entry, participants averaged 61.4 years of age; 14%
      of them smoked, and 22% used aspirin. At the baseline colonoscopy, 35% of
      participants had two or more adenomas, and 29% had at least one large (> of = 1
      cm) adenoma. Demographic, behavioral, dietary, and clinical characteristics are
      comparable across the two study arms. Participants have repeat colonoscopies
      after 1 (T(1)) and 4 (T(4)) years of follow-up. The primary end point is adenoma
      recurrence; secondary end points include number, size, location, and histology of
      adenomas. All resected lesions are reviewed centrally by gastrointestinal
      pathologists. The trial provides 90% power to detect a reduction of 24% in the
      annual adenoma recurrence rate. The primary analytic period, on which sample size
      calculations were based is 3 years (T(1) to T(4)), which permits a 1-year lag
      time for the intervention to work and allows a more definitive clearing of
      lesions at T(1), given that at least 10-15% of polyps may be missed at baseline.
      The final (T(4)) colonoscopies are expected to be completed in early 1998.

PMID- 9162305
TI  - The polyp prevention trial II: dietary intervention program and participant
      baseline dietary characteristics.
AB  - The Polyp Prevention Trial (PPT) is a multicenter randomized controlled trial to
      evaluate whether a low-fat, high-dietary fiber, high-fruit and -vegetable eating
      pattern will reduce the recurrence of adenomatous polyps of the large bowel. Men
      and women who had one or more adenomas removed recently were randomized into
      either the intervention (n = 1037) or control (n = 1042) arms. Food frequency
      questionnaire data indicate that PPT participants at the beginning of the trial
      consumed 36.8% of total energy from fat, 9.7 g of dietary fiber/1000 kcal, and
      3.8 daily servings of fruits and vegetables. Baseline dietary characteristics,
      including intake of fat, fiber, and fruits and vegetables, as well as other macro
      and micronutrients, were similar in the two study groups. The intervention
      participants receive extensive dietary and behavioral counseling to achieve the
      PPT dietary goals of 20% of total energy from fat, 18 g/1000 kcal of dietary
      fiber, and 5-8 daily servings (depending on total caloric intake) of fruits and
      vegetables. Control participants do not receive such counseling and are expected
      to continue their usual intake. Dietary intake in both groups is mentioned
      annually using a 4-day food record (also completed at 6 months by intervention
      participants only) and a food frequency questionnaire, with a 10% random sample
      of participants completing an annual unscheduled 24-h telephone recall. Blood
      specimens are drawn and analyzed annually for lipids and carotenoids. This
      article provides details on the rationale and design of the PPT dietary
      intervention program and describes the participant baseline dietary intake data
      characteristics.

PMID- 9162307
TI  - Cigarette smoking and breast cancer.
AB  - A priori hypotheses suggest that cigarette smoking could either increase or
      decrease breast cancer incidence. To clarify these competing hypotheses, we used
      data from a very large population-based breast cancer case-control study to
      investigate the impact of smoking on breast cancer risk. Breast cancer patients
      less than 75 years old were identified from statewide tumor registries in
      Wisconsin, Massachusetts, Maine, and New Hampshire; controls were randomly
      selected from driver's license lists (age less than 65) or lists of Medicare
      beneficiaries (age 65-74). Information on reproductive history, medical history,
      and personal habits including cigarette smoking was obtained by telephone
      interview. A total of 6,888 cases and 9,529 controls were interviewed. There was
      virtually no relationship between current smoking and breast cancer risk
      (multivariate odds ratio, 1.00; 95% confidence interval, 0.92-1.09), and former
      smokers had a barely increased risk (odds ratio, 1.10; 95% confidence interval,
      1.01-1.19). Similar results were observed among both premenopausal and
      postmenopausal women. There was no suggestion that heavy or long-term smoking
      increased or decreased risk, nor were there indications that women who began
      smoking at an early age were at increased risk, as has been hypothesized. The
      results of this large population-based study indicate that smoking does not
      influence the risk of breast cancer, even among heavy smokers who began smoking
      at an early age.

PMID- 9162306
TI  - Hepatocellular carcinoma in patients from northern Sweden with acute intermittent
      porphyria: morphology and mutations.
AB  - More than a decade ago an association between acute intermittent porphyria (AIP)
      and hepatocellular carcinoma (HCC) was reported, but still the cause of the
      increased prevalence is unknown. Paraffin sections of formalin-fixed HCC from 17
      AIP patients were reexamined and also screened for relevant mutations using
      several methods. The tumor diagnosis was verified, and in several cases
      precirrhosis and cirrhosis were also found. The clinically founded AIP diagnosis
      was verified at the gene level in most cases, demonstrating the Norrland type of
      mutation, i.e., G(593)-to-A substitution in codon 198 of the porphobilinogen
      deaminase (PBGD) gene. The second allele was neither mutated nor missing,
      contradicting the possibility that the PBGD gene might function as a tumor
      suppressor gene. Subsequent sequencing showed that cases not cleaved by the
      restriction enzyme NheI lacked the specific Norrland mutation. In recent years,
      selective mutations at codons 249 and 166 of the p53 gene have been described in
      HCC associated with aflatoxin and hepatitis B virus. In our area, with low
      exposure to those agents, no mutations in codon 249 were found, and mutation in
      codon 166 was excluded in all tumors except one; no traces of hepatitis B DNA
      were observed. Nor did we find mutations in H-ras 12 or 61. Intrinsic aberrations
      in AIP, including reduced heme synthesis and endogenous oxidative damage to DNA,
      may incite carcinogenic mutations elsewhere in the genome of liver cells. The
      increased cell proliferation coupled to precirrhosis and cirrhosis perhaps
      represents promotion in the initiation-promotion sequence of
      hepatocarcinogenesis.

PMID- 9162308
TI  - Reproducibility of an esophageal biopsy sampling procedure in a high-incidence
      area for esophageal cancer in northern China.
AB  - The objective of this study was to evaluate the reproducibility of the biopsy
      sampling procedure in research on esophageal lesions. Biopsies were taken from
      the middle and lower thirds of the esophagus, one from each site, from 25
      subjects in a high-incidence area for esophageal cancer in Xinye County of Henan
      Province, China. The biopsy sampling procedure was repeated on the same subjects
      10 days later. When the biopsies were analyzed together and those with worse
      pathologies were used for diagnosis, 52% of the subjects had the same grade of
      lesions in the second biopsy examination, 32% had lower-grade lesions, and 16%
      had higher-grade lesions.

PMID- 9162309
TI  - A simplified method to quantify isoflavones in commercial soybean diets and human
      urine after legume consumption.

PMID- 9162311
TI  - [Role of target cells in cytolysis, induced by lymphokine-activated killer
      cells].

PMID- 9162310
TI  - [Smallpox virus codes a protein that suppresses the antiviral activity of human
      gamma-interferon].

PMID- 9162313
TI  - [Mechanism of multicellular animal behavior determined by genetics].

PMID- 9162312
TI  - [Effect of 1-chloromethylsilatrane on healing of experimental open bone
      fractures].

PMID- 9162314
TI  - [Pulmonary function tests and bronchoalveolar lavage in sarcoidosis patients with
      1changes and without changes in high resolution computed tomography].
AB  - In 20 sarcoidosis patients with I0 of radiological changes the high resolution
      computed tomography (HRCT), pulmonary function tests (spirometry, diffusion
      capacity, static compliance) and broncho-alveolar lavage (BAL) were performed. In
      8 patients with pathological changes detected in HRCT and in 12 patients without
      HRCT changes the similar pulmonary function disturbances and BAL-cell count were
      observed.

PMID- 9162315
TI  - [Selective increase of gamma delta T lymphocytes in peripheral blood of patients
      with pulmonary tuberculosis according to the kind and stage of disease].
AB  - The aim of this study was to evaluate the distribution of gamma tau T cells
      expressing gd T cell receptor (TCR) in the peripheral blood of 42 patients with
      pulmonary tuberculosis before, and during the treatment. Control groups were 15
      healthy individuals and 17 patients with non granulomatous diseases. In these
      groups number of g/d T cells were 240 and 239 cells/ml and percentage 9.8 and
      12.3, respectively. Using direct immunofluorescence with the anti-gamma delta TCR
      monoclonal antibodies followed by microscopy analysis, the total number and the
      percentage of gamma delta T cells in purified peripheral blood mononuclear cells
      (PBMC) was analyzed. Expression of CD4, was determined. The observation period
      amounted to 12 weeks of the initial treatment. The total number of gamma delta
      TCR in blood of tuberculous patients was 704 cells/ml and 40% respectively, and
      normalized during the treatment. An inverse correlation was found with the
      proportion of CD4+ cells in blood.

PMID- 9162316
TI  - [Evaluation of treatment outcome for pulmonary tuberculosis with early
      introduction of intermittent methods, two years after the conclusion of
      treatment].
AB  - This publication is a continuation of our study for the treatment of pulmonary
      tuberculosis with early introduction of the intermittent methods. Early results
      were presented in a preliminary reports (Pneumonol. Alergol. Pol., 1995, 63, 57).
      From among 33 patients who were treated in this way, two-year follow-up was
      performed in 29 persons (we lost contact with two persons, 1 patient died from
      other reasons, and the next one was excluded for ambulatory prolongation of II
      phase of the treatment). 15 patients were supervised directly in our Department,
      and the others were estimated from records of Regional Antituberculosis
      Outpatient Clinics. Two years after the completion of therapy all 29 patients
      remained smear-negative and radiologically stable. On this basis, we assumed that
      results of the treatment of smear-positive pulmonary tuberculosis with early
      introduction of the intermittent methods are as good as standard therapy.

PMID- 9162317
TI  - [Tuberculous meningoencephalitis from personal material].
AB  - Clinical characteristics of 6 patients with tuberculous meningoencephalitis is
      presented. The increased morbidity of tuberculosis in recent years makes it
      necessary to consider this etiology in the diagnosis of CNS infections especially
      with severe atypic and long lasting course. In the case when tuberculous etiology
      is suspected the anti tuberculous treatment should be applied. Using new and
      modern diagnostic methods of CSF will allow to diagnose tuberculous
      meningoencephalitis earlier and will improve prognosis in this disease.

PMID- 9162318
TI  - [Drug resistance among patients with tuberculosis].
AB  - Detailed questionnaire has been received from 365 patients with drug resistant
      tuberculosis. They represented 75% of all such patients in Poland. 360 of them
      had pulmonary tuberculosis. 76% were men. Among 365 analysed patients 55% were
      below the age of 50 (of whom 61% had initial drug resistance and 47% had acquired
      resistance). Among these patients 52% had initial and 48% acquired drug
      resistance. In 193 patients (i.e. 54%) resistance to one drug (in 97 patients to
      isoniazid-H, in 80 to streptomycin-S and in 5 to rifampicin-R was observed.
      Resistance to two drugs was observed in 25% of patients and among them a majority
      (57%) was resistant to H and S and 23% to H and R. In 11% of patients, resistance
      to three drugs was observed, in 8% to four drugs, and in 4% to five or more
      drugs. Multidrug resistance (at least H and R) was observed in 97 patients (25%
      of the total number) and in 76 patients resistance to other than H and R drugs
      was observed. Among the total number of analysed patients in 263 (72%) resistance
      to H was observed, in 208-to S, and in 102 to R. Among patients with initial drug
      resistance, the majority was resistant to one drug and among those with acquired
      resistance the majority was resistant to two or more drugs. On the basis of this
      analysis the estimated total initial drug resistance-2. 8% is 6-8 times lower
      than 30-40 years ago and have remained at this low level for at least 20 recent
      years. It is concluded therefore that drug resistance in Poland does not present
      any danger to the effectiveness of tuberculosis programme. Monitoring, however,
      should continue.

PMID- 9162319
TI  - [Usefulness of allergen extract Aquagen SQ-Dpt for administering bronchial
      provocation tests].
AB  - The value of the allergen extract, Aquagen SQ-Dpt, for performance of the
      bronchial provocation test in allergic asthma patients was evaluated. The studies
      were carried out on 117 patients suffering from allergic mite asthma. Bronchial
      challenge was performed according to Ryan's method. After an allergen inhalation,
      an early asthmatic reaction (EAR) and a late asthmatic reaction (LAR) may appear.
      In our studies a dual reaction (EAR and LAR) was observed in 53.8% of the
      patients, the EAR only in 27.4% and the LAR only in 2 patients. The subjects with
      the dual response demonstrated a higher sensitivity to the allergen than those
      with only the EAR. A positive, statistically significant correlation between
      specific and non-specific bronchial hyperreactivity was found. The frequency of
      the appearance particular patterns of the bronchial responses was similar to
      those published by other authors, using different allergen extracts. Aquagen SQ
      Dpt can be used to perform of the sBPT.

PMID- 9162320
TI  - [Evaluation of efficacy and tolerance of an antiasthmatic preparation--Ditec,
      consisting of low doses of disodium cromoglycate and fenoterol].
AB  - The efficacy, tolerance and, in addition, the effect of the antiasthmatic drug
      Ditec, consisting of low doses disodium cromoglycate (DSCG) and fenoterol on
      bronchial hyperreactivity (BHR) were evaluated. The studies were carried out on a
      group of 22 mild asthma patients aged from 10 to 20 years. The patients took DSCG
      during the first four weeks and then were treated with Ditec, 4 x 2 puffs, for
      next four weeks. The following parameters were evaluated: symptom score, beta 2
      agonist "taken on demand" consumption, spirometry, morning and evening PEF, and
      possible adverse effects. Decreases in the symptom score, beta 2-agonist
      consumption (mainly in Ditec period) and increase in PEF during the study were
      noted. The low doses of DSCG contained in Ditec were as effective as the 80 mg of
      this drug given previously. No statistically significant decrease in BHR after
      DSCG treatment was observed. At the end of the Ditec therapy, BHR to histamine
      markedly diminished. Because the last doses of Ditec were taken 2 hours before
      the bronchial provocation test with histamine, the increase in tolerance of
      histamine, mentioned above, was probably only due to the so-called acute effect
      of beta 2-agonist on BHR. Ditec seems to be a valuable antiasthmatic drug,
      especially for children and young persons. Unfortunately, our studies did not
      answer the additional question whether regular treatment with Ditec changes BHR.

PMID- 9162321
TI  - [Correlation of selected hemodynamic parameters of pulmonary circulation and
      indices of pulmonary function in patients with mitral stenosis].
AB  - The aim of this study was to test if the lung compliance and other indices of
      pulmonary function correlated with hemodynamic parameters in patients with
      secondary pulmonary hypertension due to mitral stenosis. 36 patients (mean age 50
      years) with mitral stenosis (mean mitral valve area-1.2 cm2), without history of
      lung diseases were analyzed in the study. 16 patients (group A) were in the II-nd
      and 20 patients (group B) were in the III-rd and IV-th NYHA class. All patients
      underwent Swan-Ganz catheterization with evaluation of pulmonary pressures,
      resistances and pulmonary veins compliance. Pulmonary function tests (spirometry,
      plethysomography, lung compliance) were also performed. In both analyzed groups
      the pulmonary artery pressure and pulmonary vein compliance correlated
      significantly with pulmonary compliance.

PMID- 9162322
TI  - [Early results of chemotherapy in patients with non-small cell lung cancer].
AB  - 59 patients with non-small cell lung cancer were treated with cisplatin (60
      mg/m2) on day 1 and etoposide (60 mg/m2) on days 1-5. The results of the
      treatment were evaluated after 4th course. Remissions were seen in 27 patients,
      17 patients had stabilization and 15-progression. The response rate in stages I
      and II was 70%, in stage III-40% and in stage IV-23%. In squamous cell carcinoma
      the response rate was 55%, in large cell carcinoma-25% and in adenocarcinoma-12%.

PMID- 9162323
TI  - [Results of treating patients with pleural empyema in relation to time of
      diagnosis].
AB  - Results of surgical treatment of 182 patients with pleural empyema were assessed.
      Patients were divided into 2 groups according to the length of time between the
      beginning of illness and the start of treatment at the thoracosurgical
      department. The first group consisted of 36 patients in whom the draining of
      empyema's chamber was applied no later than 7 days after the onset of illness.
      This treatment was effective in 31 (86%) of patients. The remaining, 14% of
      patients required operative treatment. The second group consisted of 146 patients
      who were admitted to surgical department later than 7 days from the beginning of
      disease. 33% of them required operative treatment. The results achieved in both
      groups of patients proved that the time lapse between, the beginning of disease
      and the confirmation of suppurative character of exudation, had a decisive
      influence on the surgical procedure and the final results of treatment.

PMID- 9162324
TI  - [A case of premature emphysema with hereditary alpha-1-antiproteinase
      deficiency].
AB  - A case of alpha-I-antiproteinase (AIPI) hereditary deficiency (serum
      concentration 34 mg%, determined by NOR-Partigen Assay F-my Behringer) in 41
      years old patient with premature emphysema, confirmed by phenotyping
      (isoelectrofocusing in polyacrylamide gel) phenotype PiZ is presented. Lung
      function tests showed considerable decrease (FEV1 = 1,2 l., i.e. 34% pred.,
      FEF50% = 0.55 l., i.e. 12% pred., diffusing capacity DLCO = 12.8 ml/min/mmHg,
      i.e. 43% pred.). Computed tomography revealed huge emphysematous bullae mainly in
      supradiaphragmatic parts of the lungs. The authors discuss the difficulties in
      diagnosing homozygotes with A1P1 deficiency. They suggest screening of severe
      hereditary deficiency in persons with emphysema in age interval 30-55 years. The
      presented case of premature emphysema and AIPI deficiency (confirmed by
      phenotyping variant Z) is the first in the polish literature.

PMID- 9162325
TI  - [Osteochondroplastic tracheobronchopathy].
AB  - Tracheobronchopathia osteochondroplastica (TO) 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 osseocartilaginous submucosal nodules
      projecting into the lumen of the trachea and bronchi. The mechanism of its
      occurrence remains controversial. Most cases are asymptomatic and frequently
      diagnosed incidentally during intubation, endoscopy or autopsy. The diagnosis is
      usually made on the basis of endoscopy, CT-scan and magnetic resonance. A history
      of a 79-year-old man with chronic obstructive pulmonary disease is presented.
      During bronchoscopy characteristic appearances for TO were observed. The
      diagnosis of TO was confirmed by histopathological examination of bronchial
      samples. Additionally, CT picture also suggested TO.

PMID- 9162326
TI  - [Are lung choriocarcinoma and giant cell carcinoma producing chorionic
      gonadotropins just variants of the same neoplasm?].
AB  - An article presents two cases of choriocarcinoma lung metastases. One case
      revealed the primary mediastinal choriocarcinoma and the second one had unknown
      primary localisation of the tumor, which could be suggestive of a spontaneously
      regressed primary gonadal choriocarcinoma. Authors discuss the clinico
      pathological aspects of extragonadal choriocarcinomas, theories of their
      histogenesis and the morphological similarities to anaplastic giant cell lung
      carcinoma.

PMID- 9162327
TI  - [8-year natural history of squamous cell lung cancer].
AB  - We report a patient with recognised squamous cell carcinoma of the lung, who
      refused of surgical treatment, and who was observed for next 8 years. In the last
      year of the disease the laser coagulation and palliative radiotherapy were used
      for recanalization the right bronchus. The patient died 8 years and 6 months
      after diagnosis was made.

PMID- 9162328
TI  - [Pincoffs-Bard's syndrome in a 15-year old girl].
AB  - A case of primary stomach carcinoma (or Pincoff's-Bard syndrome) with extensive
      radiologic shadows on chest X-ray and clinical signs of respiratory failure has
      been presented. The case concerned a 15-year-old girl being diagnosed in several
      hospital because of pulmonary lesions. The diagnosis was made on a basis of the
      autopsy.

PMID- 9162330
TI  - [The significance of muco-ciliary clearance as a defense mechanism in the
      respiratory tract].

PMID- 9162329
TI  - [Cellular immunity in tuberculosis particularly the role of gamma delta T
      lymphocytes].

PMID- 9162331
TI  - [The possibility of using heparin for treatment of bronchial asthma].

PMID- 9162332
TI  - [Noninvasive and invasive thymoma probes into evaluating the value of prognostic
      factors].

PMID- 9162333
TI  - [Metaplasia of the bronchial mucosa in the respiratory tract of patients with
      chronic bronchitis].

PMID- 9162334
TI  - [From the history of fighting tuberculosis on the Bielsko Voivodeship terrain].

PMID- 9162335
TI  - [Interasthma in Montpellier].

PMID- 9162336
TI  - [Report of the international symposium on allergy in Davos may 2-4, 1996].

PMID- 9162337
TI  - [Role of transrectal echography in the evaluation of obstructive seminal vesicle
      pathology in prostatitis syndrome].
AB  - Prostatitis syndromes are frequent and cause pain and discomfort in adult males.
      Non bacterial types occur more often than bacterial prostatitis. Transrectal
      ultrasound permits a perfect evaluation of prostate, seminal vesicles and
      ejaculatory ducts. Fifty-five patients affected by prostatis syndrome and with
      negative bacteriological studies, underwent transrectal ultrasonography performed
      with 7.5 MHz probe. In 38 cases (70%) we found abnormalities such as subacute
      vesiculitis, asymmetric dilation of the seminal vesicle, dilated and calcific
      ejaculatory ducts, mullerian duct cyst, utricular cyst and calcification.
      Ultrasonography is able to detect these lesions that often are responsible of the
      clinical symptom of the prostatitis syndrome, and may have a therapeutic value
      through guided transperineal needle aspiration or in the planning specific
      endoscopic surgery.

PMID- 9162338
TI  - [Calcifying giant-cell Sertoli tumor: description of a case with atypical
      echographic presentation].
AB  - Large cell calcifying Sertoli cell tumor of the testis is an extremely rare type
      of sex cord tumor with low malignant potential that occurs in the first and
      second ecades of life. Twenty-eight cases have been reported in the literature
      and, to our knowledge, only 2 had an aggressive behaviour. Patient age, tumor
      size, histological malignant patterns such as pleomorphism and high mitotic rate
      seem to heavy influence the future neoplasm malignancy. Ultrasonography imaging
      of the large cell calcifying has described in only 6 cases. We report an
      experience with a large cell calcifying Seroli cell tumor of the testis and point
      out the unusual sonographic findings. Moreover, if histologic examination
      suggests no malignant features, we suggest local excision as ideal therapy for
      the preservation of testicular parenchyma.

PMID- 9162339
TI  - [Multilocular cystic nephroma in children. Description of a case].
AB  - In paediatric age there may occur the various types of cystic renal tumor also of
      different clinical meaning; we can count among them shapes openly or potentially
      deadly, among which Wilms tumor cystic owing to haemorrhages and tumoral
      necrosis, congenital mesoblastic cystic nephroma, clear cell carcinoma, cystic,
      partially differentiated nephroblastoma (CPDN) and benign forms such as
      multilocular cystic nephroma (MLCN), cystic localized dysplasia of the kidney. In
      some cases, the differential diagnosis is difficult and it becomes only by
      histology: particularly the differential diagnosis between MLCN and CPDN,
      indistinguishable on the basis of the imaging and the macroscopic aspect, it is
      possible only by histology. It is described a case of multicystic lesion in a
      baby, male, aged twenty-two months, with an indolent mass of left side, screened
      by US and TC. The US examination has put into evidence the presence of renal with
      clean outlines of eight cms, formed by multiple small cysts, divided by thin
      regular septa . These aspects have been confirmed by TC. The histological
      examination has diagnosed a multilocular cystic nephroma, without atypias.
      Therefore, the multilocular cystic lesions of the kidney have to be considered
      potentially malignant and submitted to surgical treatment.

PMID- 9162340
TI  - [Milk of calcium renal stone: echographic diagnosis].
AB  - "Milk of calcium renal stone" (liquid renal calculosis) is a quite uncommon
      lithiasis distinguished by the presence of a semiliquid suspension of calcium
      salts or a "seed-like" sediment in a caliceal diverticulum or an ectasia segment
      of the collecting system. We reviewed 5 patients (1 male and 4 females, mean age
      48.6 years), with a history of urinary tract infection, renal pain or haematuria.
      All patients underwent renal ultrasonographic assessment in both clinostatic and
      orthostatic position. Three patients underwent intravenous pyelography before
      ultrasound. Ultrasonography showed a sonolucent "levelled" image with a posterior
      acoustic shadow inside a hydro-caliceal dilation (2 pts.) or caliceal
      diverticulum (3 pts.); the persistence of the "level" in both clinostatic and
      orthostatic position allowed an immediate diagnosis in all patients. Intravenous
      pyelography performed before renal ultrasound showed no abnormality in 1 patient
      and was misleading in two; it otherwise confirmed the diagnosis when performed
      after renal ultrasonography. Three patients underwent surgery, two patients
      refused therapy; sonographic follow-up showed no evolution of the morphologic
      picture. Once considered as exceptional, liquid renal calculosis still remains
      rare pathology and accounts for 0.6% of all the urinary lithiasis diagnosed by
      ultrasound in our series. An accurate sonographic assessment allows a reliable
      diagnosis of this particular lithiasis and an easy discrimination from solid
      lithiasis, nephrocalcinosis, medullary sponge kidney and hydropyonephrosis.
      Hence, a correct diagnosis of this rare condition lets uneffective and improper
      treatments be avoided.

PMID- 9162341
TI  - [Hyperechogenicity of the renal medulla in children: clinico-echographic
      correlations].
AB  - Increased renal medullary echogenicity by renal ultrasound associated with
      hypercalciuria and nephrocalcinosis is often present in childhood. 17 children, 9
      boys and 8 girls, aged from 8 months to 10 years were classified into three
      groups based on ultrasound findings according to Patriquin and Robitaille: type A
      faint hyperechogenic rim around the sides and tip of the medullary pyramid; type
      B more intense echogenic rim of the pyramids; type C intense echoes throughout
      the pyramid. Clinic-echographic correlations showed a pattern C in 4 children
      with distal renal tubular acidosis and in an infant treated with furosemide;
      pattern B in 3 patients having different types of tubulopathy associated with
      hypercalciuria; pattern A in 6 children with congenital tubulopathy and in 3
      children treated with vitamin D. Abdominal X-rays detected medullary calcinosis
      in 2 (11.7%) of total 17 patients. Ultrasonography appears to be an important
      tool in early diagnosis of renal medullary nephrocalcinosis.

PMID- 9162342
TI  - [Role of echography in the diagnosis of urethral stenosis].
AB  - A recently developed ultrasonographic technique was described to evaluate the
      anterior urethra in 10 men suspected to have urethral stenoses. With the patient
      in frog leg position, during a perfusion of the urethra with saline through a
      catheter positioned at the beginning of the urethra, penile, transscrotal and
      transperineal scanning of the urethra was obtained. In all patients a diagnosis
      of urethral stenoses was made. After sonographic evaluation all patient underwent
      retrograde urethrogram and internal urethrotomy, that confirmed the diagnosis
      made by ultrasound. The urethral ultrasound provides valuable informations about
      the number, extent, position of the strictures and eventual scarring of the
      periurethral tissue. Urethral ultrasonography can be used as alternative imaging
      modality to the conventional radiological techniques.

PMID- 9162343
TI  - [Hemospermia: role of transrectal echography].
AB  - Hemospermia is a common benign condition, but is prevalence remains unknown, and
      can result from several causes. The etiology is idiopathic in about 50% of cases.
      The advent of transrectal ultrasonography has afforded the opportunity to best
      evaluate patients with hemospermia. Eighty patients affected by hemospermia were
      studied with Stamey test, semen analysis and culture, and transrectal
      ultrasonography (TRUS). Infection was detected in 16/80 of the cases (20%), while
      in 11/80 patients (14%) was present only excessive white blood cells in expressed
      prostatic secretions. TRUS showed abnormalities in 70/80 of patients (88%),
      including periurethral and ejaculatory calculi (42/70 pt., 60%), dilated seminal
      vesicles (22/70 pt., 31.4%) and mullerian duct cyst (6/70 pt., 8.6%). Stamey test
      and TRUS are the more usefulness investigations in hemospermia, since they can
      demonstrate the pathologic causes in about 90% of the cases.

PMID- 9162344
TI  - [Relationship between prenatal and postnatal echographic diagnosis of uropathy:
      is mass screening useful?].
AB  - Urinary tract malformations have a 1-2% incidence. An early diagnosis of these
      defects allows to realize as fast as possible the best medical and/or surgical
      treatment, preventing or at least slowing down the evolution toward chronic renal
      failure. Urinary tract malformations are particularly suitable for a "prevention"
      program due to their elevated incidence, to the "silent period" preceding
      complications and to the therapeutic possibilities strictly related to an early
      diagnosis. Ultrasound screening can easily identify congenital urinary tract
      abnormalities, especially obstructive ones, but unfortunately almost half of the
      cases escape even the most expert "eye". It is necessary a complete check-up
      right after birth. We tried to compare the method and the results of prenatal
      screening with the postnatal one, already used in many hospitals. We believe,
      even following our experience, that the screening for urinary tract malformations
      of all the neonatal population is a goal to pursue and achieve as soon as
      possible for its high sensitivity and specificity.

PMID- 9162345
TI  - [Echographic diagnosis of nephro-urological neoplasia in a pediatric nephrology
      center].
AB  - The use of ultrasound for the diagnosis of urologic neoplasms in simple and
      accurate. Nowadays nephrologists and urologists advocate the use of ultrasound
      and the procedure now plays a complementary role of the clinical examination. We
      present a retrospective study regarding our experience with ultrasonography in
      the diagnosis of urologic problems. In the period february 95-february 96 we
      performed 672 ultrasound examination on children ranging in age from 30 days to
      16 years. All examinations were performed using a 3.5-5 MHz real time convex
      scanner. The patients were examined in the supine position for imaging of the
      bladder and in the prone position for imaging of the kidneys. We report 3 cases
      of neoplasm of the genito-urinary tract screened with the use of ultrasounds in a
      selected paediatric population.

PMID- 9162346
TI  - [Utility of ultrasonography in patients with ambiguous external genitalia: a
      clinical case].
AB  - We report a case in which the use of ultrasonography in the perinatal evaluation
      of ambiguous genitalia could have avoided psychological, physiological and also
      medico-legal problems for the patient.

PMID- 9162347
TI  - [Color Doppler echographic monitoring of retrograde and anterograde sclero
      embolization of a left varicocele: report of 76 cases].
AB  - Varicocele, which is the most common cause of infertility in man, is detected by
      means physical examination and color Doppler sonography. We analyzed the results
      of percutaneous sclerotherapy of the spermatic veins in 76 out of 103 patients
      with varicocele: antegrade sclerotherapy was performed in 11 patients while 92
      men underwent retrograde scleroembolization. Color Doppler sonography was
      performed one month later and showed persistence of varicocele in 3 patients who
      underwent retrograde sclerotherapy. Retrograde percutaneous sclerotherapy of the
      spermatic vein represents, in our opinion, the gold standard in the treatment of
      primitive and recurrent left varicocele, because of its efficacy and minimal
      invasive nature. Antegrade sclerotherapy is an effective alternative treatment
      when retrograde access is not possible.

PMID- 9162348
TI  - [Role of dynamic penile color Doppler echography in the evaluation of the patient
      with La Peyronie's disease].
AB  - From March 1995 to February 1996, sixteen consecutive patients with Peyronie's
      Disease (PD) were routinely submitted to penile dynamic colour-coded doppler
      ultrasonography (CCDU). The test yielded normal results in 6 patients who had no
      erectile problems and in other 4 patients who conversely complained of reduced
      erectile function. In the other 6 patients who complained of reduced erectile
      function, the test pointed out pure arteriogenic failure in 1 case, pure
      venogenic failure in 4, and mixed arteriogenic and venogenic failure in 1. CCDU
      enables a precise assessment of erectile function as well of the site, kind and
      entity of the penile curvature to be corrected. These data are very useful when
      planning the surgical approach for each patient.

PMID- 9162349
TI  - [Usefulness of transvaginal echography in the study of organic pathology of the
      female urethra].
AB  - The Authors describe their experience about the use of vaginal ultrasound in the
      diagnosis of some organic disease of the female urethra. The ultrasonography was
      performed with the 5 Mhz endocavitary probe and patients in lithotomy position
      and filled bladder. With this method has been possible value the urethral and
      peri-urethral echostructure and urethral calibre during micturition. the Authors
      visualized 20 urethral diverticula, 6 stenosis, 2 carcinomas and 1 leiomyoma.
      They show the great reliability of this investigation and argue that it may be
      present as a first instrumental approach in the clinical suspicion of an organic
      pathology of the female urethra.

PMID- 9162350
TI  - [Role of expectant therapy in prostatic carcinoma of low grade and staging].
AB  - Low stage and grade prostate cancer can be treated by radical prostatectomy,
      radiotherapy and expectant therapy. Preoperative evaluation with biopsy is in
      many cases unreliable to pathological stage and grade. In this study we
      considered 31 patients with prostate cancer, evaluated with directed ultrasound
      guided biopsy (15) or with sextant biopsy (16). Sextant biopsy showed better
      results. Grading was confirmed by radical prostatectomy specimen in 62.5%. The
      role of expectant therapy is then discussed.

PMID- 9162351
TI  - [La Peyronie's disease: anatomical and functional evaluation using color Doppler
      echography].
AB  - We performed color duplex ultrasound in patients with Peyronie's disease in order
      to define the anatomy of corpora cavernosa and penile vascular abnormalities. We
      evaluated 20 patients, affected by Peyronie's disease, using echo-color-doppler
      after pharmaco-injection of PGE1 and autostimulation. We find that impotent
      patients had decreased EDV after 30 Minutes and after autostimulation; all
      patients had a normal PSV. The echo-colo-doppler is a useful tool in the
      evaluation of the penile vasculature, in patients with Peyronie disease, for its
      high sensitivity, low invasiveness, and good acceptance from patients. The
      results of this test could safely guide the therapeutic choice.

PMID- 9162352
TI  - [Transvaginal echography in the study of urinary stress incontinence].
AB  - Hypermobility of the bladder neck in response to increased intraabdominal
      pressure is one cause of stress urinary incontinence in women. Vaginal ultrasound
      (u.s.) is reliable and minimally invasive method for demonstrating bladder neck
      hypermobility. The Authors studied 50 women with S.U.I. and 40 with no history of
      S.U.I. measuring the distance from the bladder neck to the midline of the
      symphysis pubis (P.V.) and the angle between the BP line and the midline of the
      symphysis pubis (A.I.U.). The continent women were characterized by a median
      A.I.U. of 70 degrees and mean B.P. of 25.6 mm, at rest, a median A.I.U. of 80
      degrees and a mean B.P. of 20 mm. at stress. The incontinent women were
      characterized by a median A.I.U. of 80 degrees and mean P.V. of 22.5 mm. at rest,
      and a median A.I.U. of 95 degrees and mean P.V. of 10 mm. at stress. There is a
      significant difference between the two groups. The Authors recommend the vaginal
      u.s. as reliable, practical, economical and patient accepted method to study the
      bladder neck mobility.

PMID- 9162353
TI  - [Role of color Doppler echography in the diagnosis of obstructive uropathy].
AB  - Intrarenal Doppler US was performed in 20 patients with suspected renal
      obstruction and standard sonographic appearance of collecting-system dilatation.
      In 15 patients with true renal obstruction the resistive index (I.R.) was > 0.7.
      The A.A. think duplex Doppler US is a valuable addition to the standard
      sonographic evaluation to increase the diagnostic accuracy in patients with
      suspected renal obstruction.

PMID- 9162354
TI  - [Echographic features in the diagnosis of renal abscess].
AB  - The Authors emphasize sonographic aspects of Renal Abscess in early phase and in
      proclaimed disease. The advent of the sonography and its extensive use marked an
      inversion of tendency in Perinephric Abscess evolution. So it is possible to
      point out small Abscesses and in early phase. Leukocytes tags Scintiscan and CT
      can confirm the diagnostic tentative.

PMID- 9162355
TI  - [Ureteral jet in patients with benign prostatic hypertrophy: prognostic
      evaluation during single and combined therapy].
AB  - By color-Doppler ultrasound it's possible to visualize urine flow jet from ureter
      into the bladder. Aim of the study was to evaluate of ureteral jet in patients
      with benign prostatic hyperplasia before, during and after with one or two drugs
      medical therapy. Thirteen patients, aged 51-63 years, were studied; they were not
      affected by metabolic, hepatic, renal diseases and by prostate inflammation. Eco
      color Doppler p.w. (Toshiba SSA 270A) with a convex probe of 3.5 MHz was used. A
      transabdominal ultrasound study was performed, prostate volume measured and
      ureteral jet visualized before and along treatment (at six months interval) with
      Finasteride and at the end of treatment. Successively, in four patients, with
      relapse of prostatic synptomatology, a transabdominal ultrasound study was
      performed, before and along a treatment with Finasteride, 5 mg/die (Finastid,
      Neopharmed) and Terazosin hydrochloride, 5 mg/die (Teraprost, Malesci), and at
      the end of treatment.

PMID- 9162356
TI  - [The area of focal nephritis measured by echography: useful indications in
      patients with unexplained back pain in comparison with other assessments].
AB  - In some patients undergoing an U.S. study of kidney for lumbodynia, it's sometime
      possible to visualize hypoechoic and areas poorly demarcated without distal
      acoustic enhancement, localized within the cortex and disrupting the cortico
      medullary junction. These findings, called focal nephritis, associated to minimal
      retention of urine in the bladder, reflect an inflammatory process involving the
      renal parenchyma, in spite of normal urine analysis. To confirm this theory, 7
      patients who presented these findings at US study of kidney underwent renal
      scintigram with labeled granulocytes. This test revealed the presence of focal
      bacterial nephritis in the same hypoechoic areas. Therefore US study of kidney
      combined with renal scintigram is useful to diagnose inflammatory process of the
      kidney in patients complaining lumbodynia.

PMID- 9162357
TI  - [Pulsed-wave color Doppler echography of the intrarenal vessels in patients with
      insulin-dependent diabetes mellitus and incipient nephropathy].
AB  - Diabetic nephropathy affects a subset of about 40% patients with Insulin
      Dependent Diabetes Mellitus (IDDM); it also develops in a less defined percentage
      (30-50%) of patients with non Insulin-Dependent Diabetes Mellitus (NIDDM), after
      a period of 15-20 years. It is usually divided in 5 stages: the first 3 are
      characterized by renal hypertrophy and increased glomerular filtration surface
      area (I stage) followed by glomerular histological lesions (II stage) and early
      nephropathy with microalbuminuria (III stage). At these stages nephropathy is
      still reversible by medical treatment (ACE inhibitors) and good metabolic
      control. Aim of this study was to assess the usefulness of duplex sonography with
      Doppler wave form analysis in the evaluation of early diabetic nephropathy, in
      order to detected patients at risk for irreversible renal disease. Fifteen
      patients (10 males and 5 females) aged 28-46 years, affected by IDDM were
      studied; 15 healthy subjects (7 males and 8 females) aged 20-45 years composed
      the control group. All of them underwent duplex Doppler sonography of kidney; a
      scanner with a 3.5 MHz transducer (Toshiba 270 SSA) was used. All patients had
      renal function tests within normal range. Pulsatily Index (P.I.) and Resistive
      Index (R.I. of Doppler waveform were obtained at the interlobar arteries; the
      average value of 3 bilateral measurements was taken. Doppler sonography was done
      by the same authors without knowledge of the patient group (case or control).
      Both indexes (P.I. and R.I.) resulted to have higher values in patients with IDDM
      compared to controls: P.I. = 1.46 +/- 0.30 vs. 1.07 +/- 0.06, p < 0.05; R.I. =
      0.77 +/- 0.09 vs 0.60 +/- 0.03, p < 0.05. Even if our data have to be confirmed
      by further studies, they suggest that duplex Doppler sonography may be a useful
      complementary test in the evaluation of diabetic nephropathy, even in the early
      stages.

PMID- 9162358
TI  - [Prognostic value of neonatal pyelectasia diagnosed in utero].
AB  - Sixty-six children (48 male-18 female) with prenatal diagnosis of pyelectasia
      that was conformed at birth were examined between 1986-1994. All newborns carried
      out urinalysis and urine culture and performed a renal sonogram to reconfirm the
      diagnosis at 1 month of age. After 3 month of life the pelvic dilatation was
      confirmed in 61 patients while 5 showed a complete disappearance, 61 patients
      underwent micturitional cystography that evidenced 30 renal units (RU) with
      moderate to severe vesicoureteral reflux. In the patients without reflux, a
      scintigraphy was carried out with DTPA or MAG 3 and/or IVP and evidenced a
      functional junctional pathology in 32 RU and an organic junctional pathology in
      24 RU, a primary megaureter with pre-vesical stenosis in 6 RU and a pyelo
      ureteral complete double system in 4 RU. The patients with organic stenosis or
      those patients with parenchymal damage due to the vesicoureteral reflux underwent
      surgical intervention during the 1st year of life while all the remaining
      patients are continuously monitored to date with biohumoral exams and echography.
      With these results we can safely confirm the important role of the sonogram in
      the initial diagnosis of pyelectasia and to its eventual modifications in order
      to benefit the patients with a nephro-urological pathology and direct them toward
      a correct follow up.

PMID- 9162359
TI  - [Echo-guided drainage of pararenal and pelvic fluid accumulations: technique,
      indications, and results].
AB  - Percutaneous echoguided drainage of retroperitoneal collections is to be
      considered a recommendable technique which guarantees a good percentage of
      success and a complete resolution of the effusions and also gives a low
      percentage of complications. The drainage can be made through a simple
      percutaneous needle puncture or through a catheter which is kept for some days.
      The latter technique done by Seldinger or Trocar's method, guarantees more
      possibilities of success. The systemic echographic control during the post
      operatory period of the urological patients have permit to find out the high
      frequency of small fluid effusions (haematic, urinary or lymphatic) in the
      operation area; not all the collections need a treatment. The urinary collections
      or those with clinical signs of anemia have to be drained. In the presence of
      small haematic or lymphatic collections, the ultrasonography follow-up shows
      almost always a progressive volume reduction with a following disappearance.
      Percutaneous drainage has to be performed in the presence of a large collection
      (more than 5 cm of diameter), in the case of a persistent collection or when
      patient presents with clinical features of infection.

PMID- 9162361
TI  - [Treatment of a solitary renal cyst using percutaneous drainage and repeat
      alcoholization].
AB  - The Authors report their results on the treatment of simple voluminous renal cyst
      with percutaneous drainage and three times repeated sclerosis with pure alcohol
      every 24 hours. After a mean follow-up of 28 months They report a 96% of success
      with only two recurrences. Since the fair results and low invasiveness of the
      method, the Authors propose the repeated alcoholization in the treatment of
      simple voluminous renal cysts.

PMID- 9162360
TI  - [Echographic, MRI and CT features in a case of bladder endometriosis].
AB  - Endometriosis is relatively frequent in females of menstrual age and consists in
      the appearance of active endometrial tissue at site other than uterine cavity.
      Endometrial tissue has been described to colonise the urinary system,
      particularly the urinary bladder. The most common clinical features of vesical
      endometriosis are urgency and frequency, hypogastric pain and hematuria. We
      report on a case of vesical endometriosis whose presenting features were
      dysmenorrhea, stranguria and pelvic pain. MRI and CT did not provide different or
      more precise information than ultrasound scan: these findings were
      indistinguishable from an intrauterine lesion. On the contrary endovaginal
      sonography was more sensitivity than MRI and CT. Cystoscopy was negative.
      Nondiagnostic laparoscopy was performed. Patient underwent laparotomy and partial
      cystectomy. Histopatological findings demonstrated an endometriosis of the muscle
      layer of the bladder. The rarity of this condition prompted us to report on the
      problems encountered in making the differential diagnosis.

PMID- 9162362
TI  - [Acute urinary retention caused by intraprostatic cysts: diagnostic and
      therapeutic role of transrectal prostatic echography].
AB  - There are two type of congenital prostatic cyst, the mullerian duct cyst and the
      utricular cyst. They are not common and rarely symptomatic. We report a 16-year
      old male who presented with acute urinary retention and a 3-month history of
      urine stream diminished in force and reduced sperm volume. Transrectal
      ultrasonography showed a prostatic cyst in the midline near the seminal
      colliculus. Transperineal aspiration of the cyst resulted in return to normal
      miction and sperm volume.

PMID- 9162363
TI  - [Role of echography in the diagnosis, screening, and follow-up of patients with
      von Hippel-Lindau syndrome].
AB  - Von Hippel-Lindau (VHL) disease is a genetic disorder characterized by
      hemangioblastomas of the brain and spinal cord, retinal angiomas, pancreatic
      cysts, pheochromocytomas, epididymal cystadenomas and renal cysts and neoplasms.
      These disease is transmitted in an autosomal dominant fashion and the gene
      associated with transmission of VHL has been localized to the 3p25-3p26 region of
      chromosome 3. In this study we examined a family with von Hippel-Lindau disease
      established of mother and three children and five progeny. These patients were
      evaluated with urinary tract echography, computerized tomography, DNA sequencing
      with polymerase chain reactions (PCR) and SSCP analysis. The ultrasonography is
      utilized to diagnosis, screening and in the follow-up of undergone surgery
      patient's. With this study we examined the role of echography in patients with
      von Hippel-Lindau disease.

PMID- 9162364
TI  - [Echographic aspects of renal tuberculosis].
AB  - In this study the Authors examine the utility of the ultrasonographic
      investigation in the preoperative evaluation of 22 patients submitted to
      nephrectomy for tubercular lesions, comparing the informations obtained from this
      procedure with the histologic report. The renal ultrasonography execute with a
      Toshiba 3.5 Mhz probe, has been utilized to value morphology, volume, parenchymal
      echostructure and hydronephrosis. According to the Author's series, the
      ultrasonography has shown a 100% sensitivity permitting to well value the
      presence of parenchymal lesions and hydronephrosis. As regards the tubercular
      renal injuries the ultrasonography is non-specific because it does not allow to
      have pathognomonic images. The results obtained from the U.S. are overlapping to
      the Results Related from the literature for abdominal CT. The Authors argue that
      U.S., rapid and economical investigation is an efficient complement to the
      urography for an exhaustive preoperative evaluation of patients suffering from
      renal Tuberculosis.

PMID- 9162365
TI  - [Echo-guided percutaneous treatment of renal cysts: aspiration vs continuous 24
      hour drainage].
AB  - The results of 2 treatment options, percutaneous aspiration vs percutaneous
      aspiration and continuous drainage over 24 hours, in the management of simple
      renal cyst were compared. Thirteen patients were managed with aspiration alone
      (group 1) while 19 with aspiration and continuous drainage (group 2). Recurrence
      rate was 100% in group 1 and 73% in group 2 (p: n.s.). Therefore, we believe that
      the higher cost of continuous drainage are not justified.

PMID- 9162366
TI  - [Morbidity of transperineal echo-guided prostatic biopsy, our experience].
AB  - We present a review of 1245 patients undergone to ultrasound guided transperineal
      prostatic biopsy. We examined the complications' incidence of this technique to
      confirm or exclude presence of prostate cancer. Indications to a prostatic biopsy
      include an abnormal digital rectal examination, TRUS or PSA values increased.
      Single biopsy or systematic mapping of prostate were performed. For prostate
      biopsy a "Biopsy Gun" with 18 G. needle was used. Of 1245 patients, only 31
      (2.48%) showed complications. Our experience demonstrates that ultrasound guided
      transperineal prostatic biopsy is a safe and easy technique and it is well
      accepted by the patient.

PMID- 9162367
TI  - [Echo-guided biopsy of the transitional zone in the diagnosis of prostatic
      carcinoma].
AB  - Approximately 24% of prostate cancer originate in transition zone. To define the
      indications for transition zone biopsies from April 1994 to February 1996 we
      evaluated 112 men ranging in age from 56 to 84 years (mean 67.4). 94 patients
      presented elevated PSA levels and normal rectal examination (24 with negative
      prior systematic sextant biopsies). A group included 6 patients with palpable
      nodularity and normal PSA levels. A third group consisted of 12 men with
      sonographic abnormalities. Of the 112 patients evaluated 38 (34%) were found to
      have cancer on the prostate biopsies and 7 (18%) were positive only in sample of
      transition zone biopsies. We conclude that transition zone biopsies don't
      substantially improve the cancer detection rates in patients with palpable
      nodularity or sonographic abnormalities but are useful in patients with elevated
      PSA levels and/or negative prior systematic sextant biopsies.

PMID- 9162368
TI  - [Uro-gynecologic protocol for studying urinary stress incontinence].
AB  - Regarding the difficulty in using a common and standardised language in the
      diagnosis of Stress Urinary Incontinence (SUI) the authors developed a research
      protocol based on anamnestic, clinical, urodynamic and imaging forms, in order to
      have a numerous elements for the evaluation of this pathology. The preliminary
      study had to identify the most meaningful and common parameters, encoded
      according to broadly approved literature or the classification proposed by
      International Continence Society (ICS). One of the fundamental purposes was to
      clarify the role of ultrasonography technique applied to the field of Stress
      Incontinence. In this article the authors explain the choices they make, the
      technique employed for such a study and the ultrasonic images that are
      pathognomonic of the specific anatomo-functional disorders.

PMID- 9162369
TI  - [Percutaneous echo-guided drainage and sclerotherapy of symptomatic renal cysts:
      critical comparison with laparoscopic treatment].
AB  - Nowadays, the minimally invasive treatment of symptomatic renal cyst has been
      progressively gaining wide acceptance while classic open surgery has been almost
      abandoned. It is a still controversial which minimally invasive approach provides
      the major advantages and results. Fifty-two patients with symptomatic simple
      renal cyst underwent ultrasound guided percutaneous drainage and sclerotherapy
      (ethanol 95 degrees) and 20 patients underwent laparoscopic unroofing of simple
      renal cysts in our department. No major complication was recorded with both the
      techniques. Even if we reported a higher recurrence rate (82%) with sclerotherapy
      than that with laparoscopic treatment (5%) we consider the percutaneous drainage
      a valid approach because it is a safe, easy and at low cost procedure.

PMID- 9162370
TI  - [Infrequent application of intraoperative ultrasonography in urology].
AB  - Among the usual indications of intraoperative ultrasounds, we describe four
      infrequent applications that show how useful and powerful this technique could be
      for interventive urologists. The first case regards a 66 years old male who was
      affected by a renal metastasis from thoracic cage chondrosarcoma. The use of
      intraoperative ultrasounds permits to highlight atypical sonographic features of
      the secondary lesion that were not seen in preoperative radiologic exams and that
      are completely different from the usual renal lesions. The second case regards
      the treatment of prostatic abscess performed by echoguided transperineal puncture
      in which the use of transrectal ultrasound probe permits a precise and correct
      placement of the needle and the drainage in order to obtain a fast relief of the
      symptomatology. The third case shows the role of intraoperative ultrasounds in
      the localization of a parathyroid adenoma in a 52 years old male affected by
      primary hyperparathyroidism and with recurrent renal colics. In this case the
      blind surgical exploration of the parathyroid gland and so the possibility of
      iatrogenic lesions to the recurrent laryngeal nerve were avoided by the use of
      the intraoperative sonography for the identification of the adenoma. At the same
      time the operation times were reduced. The last case underlines the importance of
      using intraoperative ultrasounds in the real-time monitoring for the creation of
      the neovagina in sex reassignment surgery in male-to-female transexualism in
      order to avoid a dangerous postoperative complication represented by the
      iatrogenic lesion of the rectum during the dissection of the perineal region.

PMID- 9162371
TI  - [Echography and follow-up of prostate carcinoma: "follow up echography in the
      course of drug therapy"].
AB  - Transrectal ultrasound of the prostate (TRUS) plays a major role in the follow-up
      of hormonally treated D2 prostate cancer patients because in these situations the
      digital rectal examination (DRE) cannot be reliable in the evaluation of local
      recurrence. 82 patients with advanced prostate cancer were evaluated. Mean follow
      up was 33 months (range 3-103). TRUS was performed before starting hormonal
      therapy and every 3 months thereafter. A volume decrease of the prostate was
      obtained in 91% of the patients. The lowest mean volume of the prostate (nearly
      55% decrease of the pretreatment volume) was reached after 6-9 months of therapy.
      62.1% of the patients underwent disease progression after a mean follow-up of 25
      months (range 3-80). No correlation between systemic progression and ultrasound
      findings were observed. In 9.6% of cases a local progression was observed. In 42
      patients PSA was used in association with TRUS: the PSA nadir was reached after 6
      9 months of therapy. PSA increased in every case a disease progression was
      observed. The data showed that TRUS is an objective and reliable method in the
      follow-up of D2 prostate cancer patients. However, considering the low incidence
      of local progression, the use of PSA appears to be the standard method to monitor
      the patients, leaving TRUS in case of suspicion of local progression.

PMID- 9162372
TI  - [Echographic follow-up after radical prostatectomy].
AB  - The abdominal and transrectal ultrasound is of a great importance in the follow
      up and in the early postoperatory control in the patients which have undergone a
      radical prostatectomy. The abdominal ultrasonography can be used to identify the
      presence of abdominal or pelvic fluid collections in the postoperative period or
      to evaluating the upper urinary tract. Ultrasonography has come to play a primary
      role in the detection of lymphonodal and/or parenchymal metastasis. Transrectal
      ultrasound permits to identify the local illness relapse, whereas the
      ultrasonography examination during micturition allows the functional study of the
      bladder neck. Moreover, transrectal ultrasound is useful in guiding biopsy needle
      into a specific lesion seen on the sonogram in the perianastomotic region whereas
      random ecoguided biopsy in the perianastomotic area is necessary in patients with
      signs of recurrent cancer even in the absence of suspicious areas.

PMID- 9162373
TI  - [Developments in the last 10 years in diagnostic imaging discovery of renal
      carcinoma].
AB  - We have reviewed the files of 69 patients who had presented with cancer of the
      renal parenchyma between 1985 and 1994. In 20% of cases in 1985-1989 and in 40%
      of cases in 1990-1994 these tumours were discovered incidentally, in example
      before the occurrence of any suggestive symptoms. In 20% (1985-1989) of cases and
      40% (1990-1994) of cases, the credit for this early detection was due to
      ultrasound study prescribed by the attending physician waiting a general health
      assessment or the follow-up of some other disease. The early diagnosis treating
      cancers at less advanced staged, which will probably improve the prognosis.

PMID- 9162374
TI  - [Penile dynamic color Doppler echography in the diagnosis of erection disorders].
AB  - Penile dynamic colour-coded doppler ultrasonography (CCDU) provides reliable
      information on both hemodynamic factors, arterial inflow and veno-occlusive
      mechanism, involved in erectile function. However false negative results may
      occur due to sympathetic discharge and consequent incomplete smooth muscle
      relaxation. From March 1994 to February 1996, 150 patients suffering from ED were
      submitted to penile dynamic CCDU after high-dose (40 micrograms)
      pharmacostimulation and manual genital stimulation. False negative results
      occurred only in 3 (2%) patients. This experience suggests that high-dose
      pharmacostimulation and manual genital stimulation may reduce the occurrence of
      false negative results, further increasing the diagnostic value of CCDU.

PMID- 9162375
TI  - [Color Doppler echography in the diagnosis of nonspecific granulomatous
      prostatis: personal experience].
AB  - Non-specific granulomatous prostatitis (NSGP) is a rare but important pathology
      of the prostate because it often is confused with prostatic cancer. In fact,
      NSGP, presents at digital rectal examination as an area of increased consistency
      and painful, and at endorectal ultrasonography as an hypoechoic area with
      inhomogeneous echo structure. The frequent elevation of Prostatic-Specific
      Antigen (PSA) serum level vanish, moreover, its role of a differential factor.
      Since 1994 we used Echo-color doppler (ECD) in the evaluation of prostate cancer
      with satisfying results. The aim of our work is to value the route of ECD in the
      diagnosis of NSGP, and in the differential diagnosis with prostate cancer,
      actually only bioptic . Since January 1994 we observed 9 cases of NSGP; 7
      patients with prostatic symptomatology and 2 with PSA serum level between 4 and
      10 ng/ml. In all patients we performed endorectal US who showed, in 7 cases,
      nodular hypoechoic areas in the peripheral or central zone of the prostate, and
      in 2 cases the presence of evident BPH. In 5/7 cases with hypoechoic areas, ECD
      US showed an increase of color intensity intra-perinodular. In 2 patients with
      BPH no marked color enhancement was observed. The diagnosis of NSGP has been done
      after needle biopsy in the 7 patients with suspect nodular areas, and in the 2
      patients with BPH, after histological examination secondary to open
      prostatectomy. Our experience shows that ECD-US scanning picture in NSGP is
      superimposable with the prostatic cancer one. In fact the anatomical
      presupposition on the grounds of the "positivity" in ECD-US, focal
      hypervascularization, is present in ECD scanning pictures of both pathologies. In
      conclusion, ECD doesn't give an advantage in the differential diagnosis between
      NSGP and prostate cancer that actually remains only bioptic .

PMID- 9162377
TI  - [Renal peripelvic multicystic lymphangiectasia: is echographic diagnosis
      possible?].
AB  - We describe the role of US, in the diagnosis of LMPR and in differentiating LMPR
      from other renal disease, such as hydronephrosis and parapelvic cysts. In 10
      patients mild to moderate hydronephrosis showed at the US, bilateral in 8 cases,
      was not confirmed at IVP and CT scan evaluation. Instead, compression of the
      collecting system by multiple cysts arising from the renal sinus was revealed by
      CT scan in 8 cases and by IVP in 2. At the U.S. the profile of the calices
      appeared irregular, differing from the features of hydronephrosis; furthermore
      calices were adjacent each other, separated only by a thin membrane. All patients
      were asymptomatic. The examination of the cystic liquor and wall, obtained
      percutaneously or during surgical procedures, showed the lymphatic origin of
      them. We cannot provide definitive data regarding how to differentiate LMPR from
      hydronephrosis at U.S.. In asymptomatic patients the U.S. evidence of dilated
      calices with irregular profile and thin membrane separating each other, can
      strongly suggest the diagnosis of LMPR.

PMID- 9162376
TI  - [Sudden and unusual onset of penile plastic induration in 2 patients
      neurosurgically treated for pituitary macroadenoma].
AB  - Induratio penis plastica (IPP) or Peyronie disease is characterized by the
      developing of fibrotic plaques in the tunica albuginea of penis, that in the
      latter stages can lead to impotence. The etiology of this disease is still
      unknown even if various factors such as inflammation, autoimmunity or traumas are
      involved. Usually it occurs after 40 years of age, even if cases in young
      patients have been described. The onset of IPP can be acute in about 50% of the
      patients, while in the others it is characterized by a chronic but progressive
      progress. In this work, we describe the cases of two patients 52 and 66 years
      old, who arrived to our department for a decrease of libido and sexual potency in
      the last months. The patients were not smokers and took no drugs and they had
      never complain symptoms and signs of IPP. In both subjects an endocrine pattern
      compatible with partial hypopituitarism was present and in the first patient it
      was associated with an ACTH-dependent hypercortisolism. Pituitary imaging with
      MRI showed in both patients the presence of a mass compatible with macroadenoma,
      that in the first patient showed characteristic of invasiveness. Both subjects
      underwent transphenoidal neurosurgery with the exeresis of the neoplasia, with
      resolution of the secondary hypogonadism and reappearance of the sexual potency.
      With the resume of sexual activity the patients complained the appearance of
      painful penis bending during erection. Dynamic echographic evaluation of the
      penis with 7.5 Mhz linear probe, after the intracavernous injection of
      prostaglandin E1 10 micrograms, showed in both patients the presence of a
      hyperechogenic plaque in the tunica albuginea compatible with IPP. Both patients
      underwent successfully surgery for the excision of the plaque and the apposition
      of a patch of dura mater. The authors want to underlie as the onset of IPP can be
      sudden, promoted by the resolution of the hypogonadism secondary to pituitary
      neoplasia, and contemporary to the normalization of testosterone levels.

PMID- 9162378
TI  - [Morphological and functional aspects of the kidney in children].
AB  - Ultrasonography is useful and effective in the evaluation of renal diseases in
      pediatric age. Sonography is well established as a screening tool to evaluate the
      kidney for the presence of renal obstruction. Distinction of the obstructed from
      the non obstructed dilated collecting system is a difficult problem. Doppler
      Ultrasonography offers potential advantages in the evaluation of childhood
      genitourinary tract abnormalities.

PMID- 9162379
TI  - [Correlation between bladder echography and urodynamic examination in patients
      with multiple sclerosis].
AB  - Ultrasonography take a predominant place in the evaluation of urologic
      complications in SM patients. SM can cause urinary disorders according to entity
      and level of the primary lesion with important repercussion on the upper urinary
      tract. Aim of this work is to value the sensibility of ultrasonography in the
      identification of bladder wall abnormalities indicative of involvement of upper
      urinary tract, correlated with urodynamic evaluation. Since 1993 we performed 116
      urological ultra sound in patients with Multiple Sclerosis. We considered
      pathologic bladders with wall abnormalities or with stones, considering those
      abnormalities as secondary to altered emptying of the bladder. 65 patients showed
      wall abnormalities while 51 patients had any alteration evaluated with
      ultrasonography. In the first group the amplitude of uninhibited detrusor
      contractions was 74 cmH2O, while in the second group it was 61 cm H2O: the
      difference was statistically significant. Furthermore the incidence of upper
      tract alterations was significantly higher in the first group (p = 0.005), even
      in absence of signs of renal failure. Thus, ultrasonography demonstrated a high
      sensibility in detecting bladder conditions possibly conducive to upper urinary
      tract deterioration.

PMID- 9162380
TI  - [Echographic study of the bladder neck and prostate region after Nd-Yag laser
      treatment].
AB  - The authors describe the ultrasonic images they obtained in the follow up of
      three groups of patients who were divided according to basic pathology and
      treated with Nd: Yag Laser with contact (CLAP) and side firing (VLAP) fibers.
      Next the great differences noted between the results achieved with ultrasonic
      investigation and those obtained with flowmeter controls and IPSS are presented.
      The authors discuss the possible causes of these dissonances and hypothesize a
      new way to evaluate cervico-urethral de-obstruction: no longer an anatomical
      technique but a functional one.

PMID- 9162381
TI  - [Lobar nephritis: echographic diagnosis and follow-up].
AB  - Acute lobular nephritis is a focal bacterial infection localizer within the
      parenchyma of the kidney which may develops with abscess formation; clinical
      features of such evolution include, fever, chills, flank pain and the
      hematological findings of infective disease. Echographic pattern includes a law
      level echogenic mass with a central hypoechoic or echo-free with sometimes may
      deform renal profile. Clinical picture and echographic pattern allow the
      diagnosis of acute lobular nephritis. In the present work we report 3 cases of
      lobular nephritis on which ultrasound study has permitted the correct diagnosis
      equally to TC and RM which also was performed. Furthermore the ultrasound imaging
      is a valid method to appreciate the clinical evolution of patient during therapy.

PMID- 9162382
TI  - [Preoperative staging of prostatic carcinoma: evaluation of the role of
      transrectal echography].
AB  - Radical Retropubic Prostatectomy (RRP) is the choice treatment for localized
      prostate cancer. Transrectal ultrasonography (TRUS) was used to predict local
      tumor extension in ninety-one patients prior RRP. In these patients 41% showed
      histologic evidence of extracapsular spread. These data suggest that
      ultrasonography is associated with considerable staging errors when used to
      evaluate men with clinically localized prostate cancer.

PMID- 9162383
TI  - [Role of color Doppler echography (ECD) in the diagnosis and follow-up of post
      biopsy arteriovenous fistula in the transplanted kidney].
AB  - CCD is an helpful imaging technique during biopsy of transplanted kidney, since
      it has reduced the incidence rate of complications associated to this procedure.
      Among possible complications one of the most frequent is the arteriovenous
      fistula. We report our experience with CCD in diagnosis and monitoring of this
      complication and we underline its role in case of conservative management.

PMID- 9162384
TI  - [Functional aspects of the fetal urinary apparatus in relation to growth].
AB  - The normal and regular development of the fetal renal function is related to
      fetal growth and to the correct development of the fetal lung. Besides, the fetal
      kidneys plays an important role in the regulation of the hydro-electrolytic
      balance and in the modulation of the fetal arterial pressure. The postnatal renal
      failure is one of the most dangerous factors which may occur in the very small
      preterm babies (birth weight below 1000 g) and their therapeutical answer depends
      on the degree of kidney maturation. The knowledge of the kidney maturation
      process is one of the actual controversies in perinatal medicine. The development
      of the renal nephron and of the excretory system continues until 32-36 weeks of
      gestation, their maturation process ends only some months after birth. At 9 weeks
      of gestation the embryonic kidney may be seen in a transvaginal ultrasonographic
      scanning; the calico-pelvic system is visible from the 11th week of gestation and
      the bladder may be seen by ultrasound from the 12 weeks' gestation. The fetal
      glomerular ultrafiltration process starts at the 10-11 week of gestation and the
      most important factors that improve the volume of glomerular ultrafiltrate is the
      total renal mass which is related to the number of functional nephron units. The
      Doppler velocimetry performed on the fetal renal artery has shown that the fetal
      renal blood flow increases with the increase of the renal volume and gestational
      age and it depends on the cardiac output. In the renal artery the resistance to
      blood flow decreases with gestational age. During fetal hypoxia there is a
      reduction of the amniotic fluid production; this phenomenon is related to the
      redistribution of the fetal blood flow with a decrease of the perfusion of
      peripheric organs (as the kidney) and an increase of the perfusion of brain,
      heart, liver and adrenals. The hypoxic fetal kidney is ischemic; moreover, the
      urine production rate is diminished and the humoral response of the kidney
      increase the fetal arterial pressure which maintains the haemodynamic
      compensation to hypoxia. When this situation is prolonged, there is possibly
      renal failure. The fetal renal ultrasonographic examination can give important
      information about the maturity degree of the fetal kidney and the evaluation of
      Doppler velocimetry on renal artery and the evaluation of the amniotic fluid
      allow the monitoring of fetal hypoxia. In future the Doppler velocimetry of
      intrarenal arteries and the biochemical evaluation of the amniotic fluid may a
      real evaluation of the fetal renal function.

PMID- 9162385
TI  - [Carcinoma of the prostate: correlation between local staging and systemic
      progression].
AB  - Management of prostate cancer requires considerable economic and social efforts
      and may causes some discomfort to patient. To attempt a simplification of the
      prostate cancer follow-up (dosage of PSA, ultrasound and abdominal and pelvic TC
      and/or RM, bone scan, X-ray chest and X-ray bone), Authors have review the
      patients with prostatic cancer who were undergone to a conservative treatment
      with hormonal and/or radiation therapy. From January 1984 to September 1995, 136
      patients have been evaluated in the Urological Department of University of
      Perugia. Local staging cancer has been made according to TNM system. Ultrasound
      transrectal follow-up study (TRUS) we made through longitudinal and/or
      transversal scans. The echographic features have been evaluated are the prostate
      size, volume and echogenic pattern of cancer, extracapsular extention and,
      finally, the echographic appearance of surrounding tissues (seminal vesicles,
      rectum, bladder). In 116 patients (85.3%) Authors found a good correlation of
      clinical course and the results of the investigations whereas in 20 patients
      (14.7%) such correlation falls to be demonstrated. Although PSA level remains an
      important prognostic marker for monitoring patients with prostatic cancer, TRUS
      is useful to determinate not only the local status but also to predict the
      subsequent clinical course of these patients. The later could be performed at
      least twice a year whereas further investigations could be prescribed only in
      presence of clinical suspicious of metastasis. It can be concluded that TRUS and
      PSA levels are sufficiently safe indexes on follow-up of prostate cancer which
      can replace the most expensive examinations avoiding an unnecessary cost to the
      health care system. Furthermore TRUS can recognize patients with urine flow
      obstruction who may benefit by treatment with improvement of their quality of
      life.

PMID- 9162386
TI  - [The development of local nonexcitability in sinus node cells and other cells
      with diastolic depolarization in the right atrium of the rabbit under the action
      of acetylcholine].
AB  - The sinus node is heterogeneous structure. In the intact sinus node acetylcholine
      induced shift of pacemaker from the center of sinus node suggesting higher
      sensitivity of typical pacemaker cells to acetylcholine. The aim of this study
      was to compare the acetylcholine (10(-5), 10(-4) M) action on different cell
      types in the intercaval region as well as in the sinus node. The rabbit right
      atrium, with the sinus node region intact, was pinned in a tissue bath. One or
      two microelectrodes were impaled in the sinus node and atrial electrogram was
      obtained simultaneously. During superfusion with acetylcholine though the
      preparations retained regular rhythm some of the cells with diastolic
      depolarization became inexcitable, their amplitude fell below 30% of the control
      value while others did not. In pacemaker cells (upstroke velocity < 5 V/s; smooth
      transition from diastolic depolarization into upstroke) occurrence of
      inexcitability was the highest: 36 of 40 cells (90%). With increasing upstroke
      velocity, the occurrence of inexcitability decreased. Effects of acetylcholine
      were completely reversible and were blocked by pretreatment with atropine 10(-7)
      M. It may be suggested that particular sensitivity of typical pacemaker cells to
      acetylcholine could arise from two facts: 1. In typical pacemaker cells calcium
      current plays the main role in action potential upstroke; 2. The calcium current
      in the sinus node cells is particular sensitive to acetylcholine.

PMID- 9162387
TI  - [The initiation of cold shivering during the local heating of the rat
      hypothalamus under immersion hypothermia].
AB  - A local artificial heating of the hypothalamic centre of thermoregulation in rats
      subjected to immersion cooling to a deep hypothermia activated a shivering. The
      data obtained suggest that one of the reasons of disorders in the organism
      thermoregulatory functions under conditions of a deep hypothermia involves a
      direct effect of the cold upon the thermoregulation centre in the hypothalamus.

PMID- 9162388
TI  - [The maximal duration of respiratory arrest during hypothermia in white rats
      which it is possible to reverse by an increase in brain temperature].
AB  - Animals were cooled to 9-10 C, and the maximal reversible respiration arrest
      lasted 3.5 min. Irreversibility of the respiration arrest lasting longer than 3.5
      min. seems to be due to the fact that increasing the brain temperature induces a
      discrepancy between the oxygen demand of the tissues and its contents which would
      lead to a brain hypoxia and its death.

PMID- 9162389
TI  - [Rhythmic stimulation: its effect on periodic processes and on the functional
      status of the cortical neurons in the rabbit during aging].

PMID- 9162390
TI  - [An automated system for determining tracheobronchial resistance].

PMID- 9162391
TI  - [A device for the restraint of laboratory rats in research on their gastric
      secretion].

PMID- 9162392
TI  - [The functional significance of alpha activity in the visual cortex for the
      recognition of images and movement].
AB  - The idea of the EEG alpha-waves as a rhythmically spreading scanning process was
      tested in 27 subjects. The stimuli presentation was not synchronised with the
      alpha-wave phase in control. In experimental group, recognition of different
      shape figures and size coincided with one of four phases of the EEG alpha-wave in
      occipital area. Under flicker stimulation through closed eyes with the alpha
      frequency, 11 of the 12 subjects perceived distinct illusory visual objects. The
      optimal stimulation frequency was always within the alpha-range and closely
      correlated with the individual predominant alpha-frequency. The data obtained
      corroborate the theory that the alpha-wave in the visual cortex reflects a
      uniformity of the spreading scanning process which plays a major part in the
      process of visual recognition.

PMID- 9162394
TI  - [An echographic study of the heart of the hen (Gallus domesticus)].
AB  - Linear size of cavities and ventricular walls, aorta, as well as the valves
      movements were determined by means of echography in adult chickens during the
      heart systole-diastole. The volume parameters were assessed.

PMID- 9162393
TI  - [Heart functions in monkeys during a 2-week antiorthostatic hypokinesia].
AB  - Dynamics of the left heart ventricular muscle contractility and compliance was
      studied in 4 monkeys in the head down position (antiorthostatic hypokinesia) with
      the body angle 10 during 2 weeks. Functional tests on a tilt table and under two
      conditions of centrifuge rotation were performed prior to and after the
      antiorthostatic hypokinesia. No changes in the left heart ventricular muscle
      contractility was found. However, the sensitivity level of the baroreflex control
      decreased. Compliance of the left heart myocardial fibre increased in the first
      hours and days of the antiorthostatic hypokinesia.

PMID- 9162395
TI  - [The vasomotor effects of the enzymes of the fibrinolytic system in rats].
AB  - Human plasmin (Pm) caused a rapid dose-dependent relaxation of norepinephrine
      preconstricted isolated aortic ring and vascular net in the Wistar rat hindlimbs.
      Neither atropine, nor obsidan or indomethacin suppressed the Pm-induced
      vasodilatation of the aortic ring. Mechanical removal of endothelium and NO
      blocker N-Nitro-L-Arg almost completely abolished the Pm-induced relaxation. DIP
      Pm, AN-Pm and Glu-plasminogen did not change the vascular tone of the
      preconstricted rings. Both aprotinin and E-aminocapronic acid inhibited the
      relaxing effect of the Pm. Besides the circulating Pm, the enzyme forming on the
      endothelial surface from plasminogen under the action of urokinase, produced the
      vascular dilatation as well.

PMID- 9162396
TI  - [The components of the negative chronotropic effect of the vagus nerve on the
      heart and a method for their definition].
AB  - Stimulation of the peripheral end of the right n.vagus led to synchronizing of
      the vagal and cardiac rhythms in anesthetised cats. The stimulation of the
      n.vagus beyond the synchronizing range resulted in the sinus arrhythmia. The
      negative chronotropic effect of the vagus nerve on the heart was shown to consist
      of tonic as well as synchronizing components. The latter component did not depend
      on the heart rate and may be expressed as a difference between the maximal and
      minimal cardiac cycle during the sinus arrhythmia. The tonic component was
      determined as a difference between the initial cardiac cycle and the minimal
      cardiac cycle during the sinus arrhythmia. It seems to be cumulative in nature
      and to depend on the heart rate.

PMID- 9162397
TI  - [The effect of plaferon on cerebral circulatory hypoxia in rabbits].
AB  - Local cerebral blood flow (LCBF) was reduced following plaferon administration in
      rabbits due to impairment of the vasodilator responses of cerebral vessels or
      their transformation into vasoconstrictor responses, the effect being added to
      that of vasoconstrictor responses to vasoactive neuropeptides contained in
      plaferon.

PMID- 9162398
TI  - [A rotational syndrome induced by administration of the delta sleep-inducing
      peptide into the reticular portion of the rat substantia nigra].
AB  - Unilateral intranigral administration of a delta-sleep-induced peptide (DSIP)
      evoked a contralateral rotation. Naloxon prevented development of the effect
      whereas haloperidol administration enhanced the DSIP cataleptogenic effect.

PMID- 9162399
TI  - [An estimation of the contrast sensitivity of kittens after termination of the
      critical developmental period].
AB  - Special contrast sensitivity was estimated in kittens at the age of 6, 9 and 12
      months as well as in adult cats. Acuteness of perception of grating pattern
      remained the same in kittens of 6 as well as 12 months of age. However, the
      former kittens were shown to have a decreased contrast sensitivity at lower
      spatial frequencies (cycles/degree). The contrast sensitivity reached the adult
      level at 12-month age. This seems to reflect a maturation of the higher cortical
      areas involved in the recognition process.

PMID- 9162400
TI  - [The physiological characteristics of genetic predisposition to catalepsy in rats
      depending on the stage of selection].
AB  - Male rats with a genetic predisposition to cataleptic reactions revealed a
      reduced motor activity and a diminished activation of mineralocorticoid and
      testosterone synthesis in response to a mild stress as compared with the Wistar
      rats. The reactions, however, were exactly opposite in the Wistar rats with signs
      of cataleptic features. The data obtained suggest that, when creating genetic
      animal models of human diseases, the initial stages of breeding should correspond
      to early stages of the disease whereas advanced stages of breeding are similar to
      later, chronic phases of the disease.

PMID- 9162401
TI  - [The interaction of GABA-A receptors with the serotoninergic system of the brain
      in regulating the testosterone level by the negative feedback mechanism].
AB  - A unilateral hemicastration decreased the serotonin and 5-hydroxyindolacetic acid
      levels in the Wistar rat mediobasal hypothalamus, but not in the midbrain. These
      neurotransmitters were shown to interact in the process of androgen restoration
      after the hemicastration. The maximal contribution of GABAergic mechanisms in the
      testosterone feedback regulation involves the GABA effect via the central GABA-A
      receptors of the mediobasal hypothalamus' serotoninergic neurons, thus activating
      the hormone level restoration. The GABA seems to induce a serotonin-independent
      inhibition of the testosterone level stabilising after hemicastration.

PMID- 9162402
TI  - [The dynamics of the somatotropin content in the follicular fluid during
      maturation and atresia of the antral follicles in bovine ovaries].
AB  - Somatotropin level was shown to rise in follicular fluid from bovine ovaries
      during the follicular growth stage with increasing of the follicular diameter
      from 3-5 to 6-10 mm. Follicles with the diameter of 10-20 mm containing over 40%
      of pycnotic granulosa cells revealed lower levels of somatotropin in their fluid
      as compared with those containing 20% or lesser amount of pycnotic cells. The
      data obtained suggest a direct involvement of somatotropin in regulation of the
      growth and atretic processes in antral bovine ovarian follicles.

PMID- 9162403
TI  - [The biochemical changes in the blood of variously adapted persons under exposure
      to different physical loads who develop tolerance].
AB  - Study of the energy metabolism indices and those of acid-alkaline balance in
      highly trained sportsmen and in the beginners revealed a dependence of the
      organism biochemical changes on intensity of physical loads, thus indicating a
      direct relationship between the energy metabolism rate and the degree of the
      athletes organism's adaptation. The study revealed fluctuations of regenerative
      processes during 24 hours and specified the contribution of each energy source to
      energy production under a variety of physical load. A growing adaptation of the
      athlete organism to physical loads results in a stronger correlation ties among
      separate indices of the energy metabolism.

PMID- 9162404
TI  - [The status of the gastric and duodenal mucosa, biopsied from those who worked in
      the cleanup of the aftermath of the accident at the Chernobyl Atomic Electric
      Power Station, in an organotypic tissue culture].
AB  - Biopsies of stomach and duodenum different regions mucosa obtained from patients
      with gastroduodenitis (liquidators of consequences of accident in Chernobyl
      nuclear station--LCA CNS-- and control patients) were studied cultured in vitro.
      The following are the differences found. Mononuclear cells, differentiating into
      macrophages were exposed from control biopsies. Mononuclear cells exposed from
      LCA CNS biopsies formed rosette-like accumulations after mitotic dividing on a
      distance from the explant. Part of cells within the rosettes acquired processes
      and formed syncytial structure.

PMID- 9162405
TI  - [The cytogenesis and differentiation of the epithelial endocrinocytes of the
      large intestine in hens and rats in ontogeny].
AB  - Cytogenesis and differentiation of epithelial endocrinocytes were studied by
      methods of histochemistry and electron microscopy in large intestine of hen and
      rat in the course of their individual development. In the embryogenesis processes
      of cellular and organospecific differentiation occur in epithelium of these
      animals large intestine, which is proved by early revealing of endocrinocytes,
      when epithelial plast is yet undifferentiated. Growth of differentiation in hen
      and rats is marked on day 19-21 of postnatal embryonal development. In postnatal
      ontogenesis endocrine apparatus achieves definitive state by day 5 in hen and day
      20 in rats. Argentaffin cells are the leading sub-population, which reflects the
      importance of serotonine they produce in realizing regulatory reactions of the
      organism. Slightly differentiated cells are the source of endocrinocyte
      cytogenesis.

PMID- 9162406
TI  - [The anatomicofunctional characteristics of the hip joint].
AB  - 32 femurs and 23 cotyloid cavities of people who died in accidents and also 29
      locked hip joints of just-received cadavers of patients died from somatic
      diseases were studied by macroscopic methods. The results confirmed that femur
      head is being nourished from the obturator artery basin. Shape and other
      parameters of ligament of the costal head so as its possible absence in the hip
      joint were found to result from interrelations between cotyloid cavity and head
      of the femur. Ligament of the costal head is maximally strained in extreme femur
      adduction and in all other positions it is more or less relaxed. This indicates
      the lack of essential mechanical role of ligament of costal head in hip joint
      biomechanics. The data obtained substantiate the possibility of using the
      ligament as a nutritive vascular peduncle of an osteochondral autograft, excised
      from lower internal region of femur head.

PMID- 9162407
TI  - [The tissue and cell defense mechanisms of the oral mucosa].
AB  - The modern concepts of tissue and cell defense mechanisms in oral mucosa are
      discussed. These mechanisms include (a) physical barriers (of epithelium and
      lamina propria), (b) non-specific antimicrobial humoral factors, (c) non-specific
      cellular defense mechanisms, (d) specific immune humoral and cell-mediated
      defense mechanisms, (c) saliva, containing both non-specific and specific
      antimicrobial factors. Special reference is given to antigen-presenting dendritic
      cells and various lymphocyte subpopulations both in epithelium and in lamina
      propria. The interaction of different cell and tissue defense mechanisms and
      their regional variations are briefly characterized.

PMID- 9162408
TI  - [Changes in the cerebral cortex in closed craniocerebral trauma of gunshot origin
      (experimental research)].
AB  - Cerebral cortex was studied morphologically in rabbits with concussion of brain
      induced by gunshot injury. The extent of severity was modelled by the bullet
      rate. No significant bleeding followed the injury allowing to observe the animals
      during the necessary terms (7-14 d.) Morphological study included light optical
      and electron microscopy. In neurons, glial cells and synapses a series of
      essential destructive changes in shown detectable predominantly on
      ultrastructural level that might be the base of psychoneurological complications
      of a distant period. Ballistic properties of a bullet were obviously fundamental
      to pathogenesis of brain concussion in these experiments as kinetic energy of the
      bullet was only sufficient for non significant damage of the skull soft tissue.
      But in contrast to the dull trauma, the blow was of a high speed and despite mild
      clinical characteristics caused essential diffuse structural disturbances in
      brain tissues.

PMID- 9162409
TI  - [The role of preparation LB in forming a thrombotic infarct of the cerebral
      cortex].
AB  - Non-invasion model for photochemically induced brain infarction was used to study
      the effect of a the new anti-ischemic drug LB ("Plaferon") in albino rats.
      Intensity of a local blood flow was measured so as oxygen tension in brain
      cortex. Square and volume of the disturbed nervous tissue region, capillary
      length and density of distribution of different caliber vessels were detected by
      means of light microscopy in serial sections of brain cortex. Preliminary
      introduction of LB was found to prevent formation of thrombotic infarction (the
      volume of cortical zone damaged is 85% lower as compared to the control). Anti
      ischemic effect of LB implicates in vasodilatory action on cerebral vessels and
      also breaking pathogenic chain of ischemia development.

PMID- 9162411
TI  - [The organization of the cortical projection system of the putamen in dogs].
AB  - Organization of cortical projections in dorsal and ventral segments of putamen
      rostral and caudal regions was studied in dogs using retrograde axonal transport
      of horse radish peroxidase. Dorsal region was shown to receive projections from
      neo- and mesocortex, while ventral is linked with all cortical units: neo-, meso-
      and allocortex. Dorsal part of putamen is to greater extent connected with
      cortical fields, relating to motor aspects of behavior (motor, premotor and
      somatosensory). Ventral region basically receives projections from the so called
      limbic cortical fields (cingular, insulary, orbital, periamygdalary and
      perirhinal). However, results of the present study do not allow to conclude on
      absolute division of projections of functionally different systems and only
      indicate the prevalence of one of them in certain topographic zone of the
      structure studied, i.e. elements of distinctive topography. consisting in
      presence of dorsal motor and ventral limbic morpho-functional regions are
      characteristic for dog putamen. No diversities in distribution of cortical
      projectional fibres along rostrocaudal axis of the structure were revealed.
      Initial neurons, projecting in putamen are of multilaminary localisation in the
      cortex.

PMID- 9162410
TI  - [The distribution of nitric-oxide synthetase in the cells of the rat cerebral
      cortex].
AB  - In the experiment performed in mature male Wistar rats using histochemical method
      of nitric oxide synthase revealing it was shown that the enzyme may be produced
      in brain by neurons, glial cells, epitheliocytes of vascular plexuses of lateral
      ventricles and endotheliocytes of different caliber vessels. Distribution of
      nitric oxide synthase in neurons and their processes indicate the possibility of
      both post- and presynaptic localisation of the enzyme.

PMID- 9162412
TI  - [The neurochemical characteristics of the neurons in the human hippocampal
      formation].
AB  - Distribution of activity of phosphate-activated glutaminase, aspartate
      aminotransferase (AST), choline acetyltransferase (CAT) and gamma-aminobutyric
      acid transaminase (gamma-Abu T) in brain hippocampal formation was studied in 6
      people aged 23-65 years using histochemical methods. AST marks axonic systems in
      neuropil layers of Ammon's horn. Glutaminase is localised in perikarya and
      proximal segments of pyramidal and granular neurons dendrites. CAT is identified
      in terminal-like dotted structures in pyramidal and granular layers and also in
      certain nonpyramidal cells of stratum lacunosum molecular of field CAI. Product
      of histochemical reaction to gamma-Abu-T stains pericellular plexuses in basis
      layers of Ammon's horn and denticulate fascia. A generalizing scheme of
      neurochemical organization of hippocampal formation links is represented in the
      study.

PMID- 9162413
TI  - [The comparative morphological aspect of the formation of the macroglial
      environment of the spinal cord motor neurons].
AB  - Ventral horns of the spinal cord obtained from 169 vertebrates (bony fish
      amphibians reptiles, birds and mammals, primates and Homo sapiens included) were
      studied Interrelations between motoneurons and macroglial cells (astrocytes and
      oligodendrocytes) were examined on light optical and electron microscopic levels.
      It was found that the higher the evolutionary grade was, the bigger grew the
      number of glial satellite from the motoneuron environment and the more
      distinctive their differentiation became. Progressive evolutionary
      reorganizations in the organism (increase of influence of brain on spinal cord,
      possibilities of motor system, change of gas dynamics between blood and tissue
      etc) resulted in morphofunctional specialization of macroglia, participating in
      neuron maintenance in mammals and especially in primates and man.

PMID- 9162414
TI  - [The ultrastructure of the neuromuscular synapses at different stages in the
      development of the embryos and tadpoles of the clawed toad].
AB  - Myoneural synapses were studied in embryos and tadpole of Xenopus laevis on
      different stages of development using light and electron microscopy. On embryonal
      stages, during hatching and on stages of tadpole myoneural synapses vary in in
      appearance, number of organelles and extent of formation of different synaptic
      specialisations. During the process of myoneural contacts forming in the
      development of amphibians, terminal is the first to form, followed by the Schwann
      cell, that covers it, and postsynaptic plication forms in the last turn. When the
      embryo of Xenopus laevis becomes a tadpole some of its terminals contain
      significant number of large synaptic vesicles united into clusters both in
      cytoplasm and near to active zones (together with small ones). This heterogeneity
      was not found on earlier stages. A suggestion is made on possible participation
      of two different axons in the innervation of myotomic muscular fibres of tadpole
      of Xenopus laevis.

PMID- 9162415
TI  - [Multinuclear neurons in the ganglia of the gastrointestinal tract].
AB  - Findings of light optical and electron microscopy studies on formation of
      multinuclear neurons in gastrointestinal tract myenteric plexus in mammals
      affected by extreme factors (vagotomy, modelling of portal hypertension.
      Hyperbaric oxygenation and hypergravitation) were presented. A model for original
      transformation of multinuclear neuron as a mechanism of new nerve cells formation
      in the course of the organism compensatory-adaptive reaction to extreme action
      was obtained.

PMID- 9162416
TI  - [The journal Morfologiia is 80 years old].

PMID- 9162417
TI  - [The reaction of the cytoskeleton and smooth endoplasmic reticulum of Mauthner's
      neurons in goldfish to partial denervation and prolonged sensory stimulation].
AB  - Structure of smooth endoplasmic reticulum and cytoskeleton of goldfish Mauthner
      neurons were studied together with the behavior of fish after partial
      deafferentation of one of the dendrites with following long-term natural
      stimulation of another one and soma. Strong disturbance of cytoskeleton and
      proliferation of smooth endoplasmic reticulum especially of its transversely
      localised component accompanies exhaustion of Mauthner neurons caused by
      stimulation in normal absolute afferentation. On behavioral level it is manifests
      in significant suppression of fish motor activity. Similar stimulation of partly
      deafferentated Mauthner neurons turns to be more sparing both for fish behaviour
      and Mauthner neurons structure. Proliferation of endoplasmic reticulum was not in
      fact observed and in the cytoskeleton bundles of filaments were detected which
      implies improvement of its physico-chemical characteristics and increase of
      resistance to external factors. Probably, this relative resistance of partly
      deafferentated Mauthner neurons of fish to long-term natural stimulation is
      conditioned predominantly by postsynaptic mechanisms and is likely linked with
      reorganization in cytoskeleton, caused by preliminary change of Mauthner neurons
      innervation.

PMID- 9162418
TI  - [The structural differences in the mesenteric vessels of rats with spontaneous
      (SHR) and DOCA-salt hypertension].
AB  - Electron microscopy study of different diameter and functional purpose
      mesenterial arteries revealed that spontaneous and DOCA-saline hypertension cause
      different ultrastructural changes in all coats with the exception of cranial
      mesenterial artery, in endotheliocytes of which no changes occurred in
      spontaneous hypertension. In cranial mesenterial artery both forms of
      hypertension cause disorder of normal media structure while in ramifications-only
      in spontaneous hypertension. Cranial mesenterial artery loses is properties in
      both forms of hypertension and in ramifications, in contrast, growth of elastic
      material is observed. In media of cranial mesentery artery in both forms
      intercellular space grows smaller, elastic membrane significantly reduces,
      myocyte layers go closer and despite their hypertrophy, vascular wall thickness
      does not change in spontaneous hypertension and increases nonsignificantly in
      DOCA-saline one. For cranial artery ramifications hypertrophy of vascular wall is
      characteristic. In spontaneous hypertension sympathetic innervation of branches
      increases, and in saline vasomotor nerves action turns weaker.

PMID- 9162419
TI  - [The endotheliocytes of the lymphatic capillary and their motor activity].
AB  - Endotheliocytes of lymphatic capillaries of different configuration were studied
      in total preparations of central tendon of diaphragm in rabbits. Between
      different cell types there are transitional forms. Argyrophilic structures in the
      form of loops, hooks and rods, located inside the endotheliocytes but linked with
      intercellular borders were described. The data obtained allowed to conclude the
      presence of motor activity of lymphatic capillaries endotheliocytes associated
      with change of their shape and border length along the cell perimeter.
      Endotheliocyte motor activity sharply increases in aseptic inflammation.
      Different endotheliocyte configuration and their perimeter length are dependent
      on the lymphatic capillaries resorptive activity.

PMID- 9162420
TI  - [The valves of the marginal sinus of the lymph nodes].
AB  - Popliteal lymph nodes of male Wistar rats were studied in scanning regime of
      electron microscope. On the base of the data obtained it is concluded that on the
      lymph node surface and in the thickness of a capsule afferent lymphatic vessels
      branch into thin rami supplied with valves from the inside of the capsule in the
      site of falling into marginal sinus. Valvular apparatus found obviously gives
      possibility to regulate lymph flow in the lymph node.

PMID- 9162421
TI  - [Structural changes in the thymus and spleen of white rats during the recovery
      after long-term physical loading].
AB  - In the experiment on 30 outbred rats, subjected to systemic long term physical
      loads it was shown that unfavourable changes in immune system organs may arise
      not only affected by acting loads but also during repair after their finishing. 2
      weeks after sharp ceasing of exercises increase of involutive changes in lymphoid
      organs (reduction of thymus and spleen sizes, disappearance of lymphoid nodules
      with germinative centers in spleen and great number of degenerating cells) so as
      decrease of the organism resistance were found. This was suggested by growth of
      pathogenic microflora colonies on the agar. In gradual reduction of physical load
      it was managed to escape from unfavourable changes in both organs.

PMID- 9162422
TI  - [The morphofunctional characteristics of the zona glomerulosa of the adrenal
      cortex in rats with hereditary stress-induced arterial hypertension].
AB  - Morphometrical analysis of adrenal cortex glomerular zone performed in rats with
      hereditary stress-induced arterial hypertension assisted in establishing
      important peculiarities of the zone structure. Adrenocorticocytes of adrenal
      cortex glomerular zone in hypertension rats are subjected to hyperplastic
      intercellular changes, suggesting the increase of the zone functional activity,
      which is substantiated by data on significantly high aldosterone concentration in
      plasma of these animals.

PMID- 9162423
TI  - [An index of the degree of development of the connective-tissue papillae in the
      human esophageal mucosa].
AB  - Morphological and morphometric analysis of esophageal mucosa demonstrated
      constant changes mucosal connective tissue undergoes during postnatal
      organogenesis. By using mathematical methods an index of development stage for
      connective tissue papillae of esophageal mucosa was detected. This index, on the
      author's opinion, is organospecific and may be turned to account when evaluating
      interrelations with the complex "epithelium-connective tissue" of mucosa in norma
      and pathology.

PMID- 9162424
TI  - The strength of achilles tendon repair: an in vitro study of the biomechanical
      behavior in human cadaver tendons.

PMID- 9162425
TI  - [Assessment of 32 months of continuous control of detection kits for anti-HIV and
      anti-HTLV antibodies and Hbs antigen used most commonly in transfusion biology.
      Retrovirus Study Group and Viral Hepatitis Study Group].
AB  - Controls were performed using a common internal panel specific for anti-HIV, anti
      HTLV and HBs Ag. During the past 32 months, 5 anti-HIV1 + 2 antibody kits
      (Abbott, Behring, Biotest, Murex D. and Organon T., total of 199 lots), 4 anti
      HTLV I/II antibody kits (Abbott, Murex D., Organon T. and Ortho C.D., total of
      153 lots) and 5 HBs Ag kits (Abbott, S.D. Pasteur, Murex D., Organon T. and Ortho
      C.D., total of 244 lots) were used and controlled by the 14 participating
      laboratories. Analysis of the results showed the values obtained for the most
      representative sample of each panel to be within the limits m +/- 2 SD in 95 to
      100% of the HIV1 + 2 kits, in 94 to 97% of the HTLV kits and in 92 to 100% of the
      HBs Ag kits. The specificity of the kits evaluated was on an average equal or
      superior to 99.5%, as required by the French Drug Agency in a blood donor
      population.

PMID- 9162426
TI  - [Rheologic study of the dissociation reaction of erythrocyte immunologic
      agglutinates: application to subgroup A erythrocytes].
AB  - Red blood cell Agglutinates can be dissociated by providing enough energy which
      may be supplied by shear stress in a viscometer. In this paper a new technique is
      proposed to determine dissociation parameters of erythrocyte immunological
      agglutinates by using a laser backscattering method. Backscattered light
      intensity increases during the process of agglutinate dissociation when a
      controlled shear stress in a transparent Couette viscometer is applied. The
      obtained curves of dissociation can be fitted by an exponential function. A
      numerical integration of the dissociation curves allows us to obtain a parameter
      associated to the energy used in the dissociation process. A satisfactory
      differentiation of erythrocyte sub-groups Al, Az, A,B and Am has been carried out
      using this technique.

PMID- 9162427
TI  - [Rationale for a trial of prevention of perinatal transmission of hepatitis C via
      specific immunoglobulins].
AB  - Vertical transmission of the HCV infection is asymptomatic, occurring in 0-25% of
      infants born to viremic mothers in Europe. Nowadays, the only preventive measure
      in to advise against breastfeeding. Favourable conditions for a seroprophylaxis
      trial in neonates at risk are the low viral charge and the absence of former
      replication or integration. Several impediments to a randomized-controlled trial
      should be considered: Epidemiological: paucity of recruitment; low risk of
      transmission; possible antenatal transmission in cases of high maternal viremia;
      risk for intrafamilial transmission. Methodological: complex randomization of the
      study groups (genotyping, quantitative PCR, activity of mothers' diseases,
      modes/durations of delivery and feeding). Ethical: a direct individual benefit is
      not clearly established; should viremic mothers be allowed to breast feed their
      babies in the absence of prophylaxis? the risk of the emergence of mutants or
      quasi-species of the transmitted hepatitis C virus in neonates; the origin and
      selection of seropositive plasma donors.

PMID- 9162428
TI  - [Screening and confirmation of anti-HCV antibodies in Tunisian blood donors].
AB  - Antibodies to Hepatitis C virus (HCV) were tested in 43000 Tunisian blood donors
      by using enzyme immuno-assay. Our results show that 0.7% (304/43000) were anti
      HVC positive. Of these 304.78 were confirmed anti-HCV positive (0.18%) by immuno
      blot, and 99 displayed an indeterminate profile. Different immune responses were
      observed: In donors with positive serologic pattern (78/304), 25.6% response
      towards whole antigens (C + NS3 + NS4 + NS5) was frequently observed (44/78)
      56.4%. Reactivity to 2 antigens was observed in 28.2% (22/78) and with 3 antigens
      in only 15.4% (12/78), with systematic reactivity to core. In donors with
      indeterminate serologic pattern (99/304) 32.5%, reactivity to non-structural
      antigen NS5 was the most frequently observed (54/99) 54.5%, reactivity to non
      structural NS3 antigen was noted in 27.3% (27/99) and to core antigen in 18.2%
      (18/99). No donors with isolated reactivity to NS4 were observed in our series.

PMID- 9162429
TI  - [Plasma-derived products: therapeutic biological products].
AB  - The status of proprietary medicinal product has been conferred upon plasma
      derived products (PDP) by the European Community in its directive issued on the
      14 of June 1989. This directive requires each Member State to comply with the
      current regulations applicable to medicinal products related to production,
      control and registration of PDP. A different evolution characterized the American
      regulation in which PDP have been classified as biological products, submitted to
      a particular regulation since 1992. These different conceptions led the authors
      to systematically review the specificities of PDP in comparison to classical
      medicinal products: plasmatic raw material, production of active ingredients and
      manufacturing of products in the same facility, divergent production of several
      products from a single starting material, infection risks and variability
      characterizing biological products, registration and distribution. The analysis
      of complementary regulation issued to adapt the pharmaceutical principles to the
      PDP shows that it does not provide all the expected answers to the specificities
      of the PDP. This shows the advantages that could be expected by giving a status
      of biological therapeutic product to the PDP. This could above all allow to
      federate qualified people and data in order to take into account more accurate
      and more immediate information about risks which may arise in very dispersed
      fields. This could also serve as a reminder of the ethical principles attached to
      the preparation of products coming from a human source.

PMID- 9162430
TI  - Metabolic disturbances in subjects predisposed for hypertension.

PMID- 9162431
TI  - Hypertension and lipids.
AB  - Hypertension and hyperlipidaemia are closely interrelated. Both belong to the
      most important risk factors of cardiovascular disease, with special emphasis on
      the premature development of atherosclerosis and its complications. The
      prevalence of both hypertension and hyperlidaemia is high; in the Polish adult
      population, like in many other countries, it amounts to 20-40% and 60-70%,
      respectively. The prevalence of hyperlipidaemia in patients with essential
      hypertension is much higher than in the normotensive subjects and both
      abnormalities markedly increase the risk of cardiovascular disease. In so called
      Familial Dyslipidaemic Hypertension, the 16 years mortality rates were 4 times
      higher than in subjects with dyslipidaemia and hypertension as single risk
      factors. The present data point to essential hypertension as a metabolic
      disorder, which may have some pathogenetic links with the derangement of lipid
      metabolism. According to the recent results, only about 15% of all hypertensives
      do not exhibit metabolic disturbances. One of the most important topics in this
      respect is the influence of antihypertensive drugs on metabolic factors, with
      special reference to lipid metabolism. Some of these drugs may have unfavourable
      action on lipid variables, while other are neutral or even beneficial. These
      differences may have great impact on the therapeutic approach to hypertensive
      patients and form the basis for the concept of individualized therapy of
      hypertension. The goal of antihypertensive therapy is not only to lower the blood
      pressure but also to influence all other factors which may be significant for the
      prognosis. Only such an integrated approach may prevent atherosclerotic
      complications and reduce the risk of cardiovascular morbidity and mortality.

PMID- 9162432
TI  - Insulin as a pressor agent: effects of 'physiological' insulin concentrations on
      finger blood pressure.
AB  - Epidemiological evidence has linked essential hypertension with impaired tissue
      sensitivity to insulin (i.e. insulin resistance) and actions which could
      contribute to elevated blood pressure include renal sodium and water retention,
      sympathetic nervous system stimulation and effects on vascular smooth muscle cell
      growth and cation balance. Although insulin has pressor effects in some animal
      models, similar changes in human studies have only been demonstrable with
      supraphysiological insulin concentrations. We have recently measured finger blood
      pressure during a two stage hyperinsulinaemic euglycaemic clamp that produced
      insulin concentrations within the 'physiological' range. The plasma insulin
      concentration increased from 7.0 +/- 0.3 mu U.ml(-1) to 28.9 +/- 0.6 mu U.ml(
      )and then to 101 +/-1.7 mu U.ml(-1) during the procedure and was associated with
      an increase in fingers but not arm systolic blood pressure during both low dose
      (i.e.+ 9.9 +/- 1.9 mmHg vs + 7.5 +/- 2.7 mmHg with control,p <0.05) and high dose
      insulin (21.9 +/- 2.3 mmHg vs 14.6 +/- 3.1 mmHg, p <0.01). Thus it appears that
      'physiological' concentrations of insulin have pressor effects on finger systolic
      blood pressure that are not detectable more proximally and it is possible that
      such changes could contribute to the development of sustained elevations of blood
      pressure.

PMID- 9162433
TI  - Insulin and hypertension: a subset analysis.

PMID- 9162434
TI  - Insulin and the sympathetic nervous system in the pathophysiology of
      hypertension.
AB  - The well-documented epidemiologic association of insulin levels and blood
      pressure have raised the possibility of a role for insulin in the pathogenesis of
      essential hypertension. The sympathetic nervous system (SNS) is a possible link
      in this relationship, since insulin is a critical mediator of dietary-induced
      changes in sympathetic activity. Insulin mediated glucose metabolism, in central
      neurons related anatomically to the ventromedial hypothalamus, mediates fasting
      induced suppression, and overfeeding-induced stimulation of the SNS. The effect
      of insulin to stimulate the SNS is readily demonstrable in humans. The
      physiological role of insulin-mediated sympathetic stimulation is in the
      regulation of dietary thermogenesis, the linkage between dietary intake and
      metabolic rate. The association of hyperinsulinemia with hypertension in the
      obese led to the hypothesis that insulin-mediated sympathetic stimulation,
      recruited in the obese to increase metabolic rate and restore energy balance, had
      the unintended consequence of increasing blood pressure. Data developed in a
      population based cohort (The Normative Aging Study, NAS) support this hypothesis
      since: obesity was associated with evidence of increased SNS activity; there was
      a demonstrable relationship between glucose and insulin levels and SNS activity;
      and blood pressure was associated with both insulin and sympathetic activity, a
      relationship that was noted in the population as a whole after adjustment for
      body mass index and body fat distribution. Interruption of hyperinsulinemia in
      obese subjects, furthermore, decreased both plasma NE level and blood pressure.
      These data provide evidence that insulin-mediated sympathetic stimulation
      contributes to hypertension in the NAS population, and that the relationship
      occurs in both obese and non-obese subjects.

PMID- 9162435
TI  - Metabolic and adrenergic characteristics of young men with insulin resistance.
AB  - The primary site of insulin resistance, as measured by the euglycaemic glucose
      clamp technique, is skeletal muscle. We used the euglycaemic hyperinsulinaemic
      glucose clamp technique to assess insulin sensitivity (glucose disposal rate,
      GDR). We aimed at clarifying the demographic, metabolic, haemorrheological,
      haemodynamic, and by mental stress test the adrenergic characteristics of 21-year
      old men grouped in tertiles according to their insulin (I) sensitivity index
      (GDR/I); insulin resistant group (GDR/I < 5.5 a.u., n = 17), intermediate group
      (5.5 < GDR/I < 9.5 a.u., n = 16) and insulin sensitive group (GDR/I > 9.5 a.u., n
      = 17). Insulin resistance was characterized by higher body mass index (p = 0.002,
      analysis of variance), triglycerides (p = 0.001), total cholesterol/high density
      lipoprotein cholesterol ratio (p = 0.002), haemoglobin (p = 0.013), haematocrit
      (p = 0.017) and resting heart rate (p = 0.041) but not resting blood pressure or
      catecholamines in arterialized blood. However, the mental stress caused by
      announcement of a forthcoming arithmetic stress test increased diastolic blood
      pressure and plasma epinephrine dependent on insulin resistance (p = 0.006 and p
      = 0.012, respectively) with a similar trend also for the maximal increases in
      heart rate and plasma norepinephrine during arithmetic. Thus, in healthy young
      men, insulin resistance is not associated with differences in baseline blood
      pressure but is characterized by higher body weight, disorders in blood lipids
      and haemorrheology and a hyperadrenergic response to mental stress that even
      involves blood pressure. We suggest that the sympathetic nervous system may be
      involved in the pathophysiology of the characteristic insulin resistance or
      metabolic cardiovascular syndrome in young men.

PMID- 9162436
TI  - The crosstalk between insulin and the sympathetic nervous system: possible
      implications in the pathogenesis of essential hypertension.
AB  - Patients with non-insulin dependent diabetes mellitus and obesity show an
      elevated risk for development of arterial hypertension, while many non-obese, non
      diabetic patients with essential hypertension display resistance to insulin
      induced glucose disposal, accompanied by hyperinsulinaemia. This close
      association has lead some investigators to postulate that insulin resistance
      could be implicated in the pathogenesis of essential hypertension. Among the
      various factors considered as potential links between insulin resistance and high
      blood pressure, the sympathetic nervous system can be considered a prime
      candidate. In particular, our recent data in hypertensive patients have
      documented that the muscle sympathetic response evoked by insulin is about
      threefold greater than that observed in normal subjects. Such finding is well in
      agreement with previous observations in hypertensives obtained with experimental
      maneuvers and extends them by showing an abnormal sympathetic response to a
      physiological stimulus like insulin, so important in every day life. Recent data
      both from our and other laboratories have clearly established that an acute
      activation of sympathetic nervous system is able to antagonize insulin-mediated
      glucose uptake in the skeletal muscle, making very real the possibility that a
      primary defect in insulin sensitivity in hypertension may be further aggravated
      by the greater sympathetic response evoked by episodic stimuli, such as
      postprandial hyperinsulinaemia. However, while insulin evokes an increase in
      sympathetic nervous activity, at same time it is able to blunt the
      vasoconstrictive effects caused by the reflex sympathetic activation. Such
      vascular modulating effect of insulin is lost in essential hypertension,
      indicating that the resistance to insulin effect in this disease is not only
      present in skeletal muscle metabolism but it is also evident at the vascular
      level.

PMID- 9162437
TI  - Obesity and the sympathetic nervous system.
AB  - Several epidemiological studies have shown that obesity represents an independent
      risk factor for development of cardiovascular diseases, including hypertension,
      myocardial ischaemia, and cardiac arrhythmias. Although the metabolic and the
      haemodynamic alterations occurring in the obese state have been well defined for
      several years, our knowledge on the sympathetic alterations occurring in this
      condition is more scarce and controversial. This paper reviews the evidence that
      human obesity is characterized by abnormalities in sympathetic cardiovascular
      control, in the light of the results of recent studies performed by employing a
      sensitive technique to assess sympathetic activity in humans, i.e.
      microneurography. Evidence is provided that sympathetic overactivity is a common
      hallmark of the obese state, even when blood pressure levels are within the
      normal range. It will also discuss the potential mechanisms responsible for this
      sympathetic activation, suggesting that overweight-related metabolic alterations,
      such as the insulin resistance state, and abnormalities in sympathetic
      cardiovascular control exerted by arterial baroreceptors may play a pathogenetic
      role. Finally, the effects of body weight reduction on the sympathetic
      overactivity which characterizes the obese state will also be examined.

PMID- 9162438
TI  - Molecular mechanisms of insulin resistance in arterial hypertension.
AB  - The associations between insulin resistance, hyperinsulinaemia, and hypertension
      are well recognized. Hyperinsulinaemia induces hypertension through increased
      renal tubular reabsorption of sodium and water, increased sympathetic nervous
      system activity, proliferation of vascular smooth muscle cells, and alterations
      of transmembrane cation transport. At physiological concentrations, insulin
      decreases urinary sodium excretion, an action mediated by binding to specific
      high-affinity receptors. Insulin resistance is present also in strains of rats
      with genetic hypertension (spontaneously hypertensive and Dahl salt-sensitive
      rats) that can be utilized as models to study the molecular mechanisms of this
      abnormality. In normal rats, the number and mRNA levels of insulin receptors in
      the kidney are inversely related with dietary sodium content, suggesting the
      existence of a feedback mechanism that limits insulin-induced sodium retention
      when extracellular fluid volume is expanded. We have investigated the
      relationships between dietary sodium intake and renal insulin receptors in
      spontaneously hypertensive rats and have found that in this strain the feedback
      mechanism is abolished. In addition, spontaneously hypertensive rats have
      decreased expression of the insulin receptor gene in the liver and decreased
      receptor autophosphorylation and phosphorylation of an endogenous substrate (IRS
      1) in liver and muscle. These observations provide a potential explanation for
      the decreased sensitivity to insulin present in spontaneously hypertensive rats.
      In these rats, the loss of the capability to down-regulate insulin receptor in
      the kidney when extracellular fluid volume is expanded can lead to further sodium
      retention and might play a role in the development and maintenance of
      hypertension.

PMID- 9162439
TI  - Posttranslational effects of protein kinase C and insulin on red cell membrane
      phosphorylation and cation heteroexchange in hypertension.
AB  - In the red blood cell membrane, sodium-proton exchange (NHE-1) exchanges
      intracellular H(+), Li(+), and Na(+) with extracellular Na(+). In hypertensives
      (HT), the maximal velocity of translocation (V max)of Na(+)/H(+) and of
      Na(+)/Li(+) exchange modes are higher, while apparent affinity for external Na(+)
      of Na(+)/Li(+) exchange and Hill's coefficient for H(+) activation of Na(+)/H(+)
      exchange are lower than in normotensive subjects (NT). We have therefore examined
      the effects of protein kinase C (PKC) and insulin on red blood cell membrane
      phosphorylation and on the kinetic properties of cation heteroexchange. In red
      cell from NT, PMA-induced activation of PKC reduced K(m) for H(+) of NHE but it
      did not affect V(max) and K(m) for Na(+). In red cell from HT, PMA-induced a
      greater PKC stimulation and membrane phosphorylation of band 3,4.1,4.9 than in NT
      and it did not significantly reduced K(m) for H(i). On the contrary, in HT PKC
      activation significantly increased Hill's coefficient of NHE. The larger
      activation of PKC in HT could be due to downregulation secondary to higher
      membrane calpain activity. Incubation of red cells with insulin decreases K(m)
      for external Na(+) and increases V(max) of Na(+)/Li(+) exchange. Therefore, we
      have examined the relationships between Na(+)-activation kinetics of Na(+)/Li(+)
      exchange and fasting insulin levels. Na(+)-stimulated Li(+) efflux was studied by
      raising Na(+)up to 300 mM isoosmotically to measure K(m) for Na(+) and V (max).
      Li(+) efflux saturated at 150 mM external Na(+)in NT but not in HT because in HT
      it exhibited a two fold higher Na(+) Km. V(max) was higher in HT than in NT. In
      hyperinsulinemic (fasting insulin > 10 mu U/ml) HT, V(max) and Na(+) Km were
      higher than in normoinsulinemic HT. In NT, hyperinsulinemia was not associated to
      abnormal kinetic properties of Na(+)/Li(+)exchange. Stepwise multiple regression
      analysis confirmed that the main determinants of a high Km were blood pressure
      and insulin. Our results show that posttranslational effects of PKC and insulin
      affect the kinetic properties of NHE-1 in red blood cells and suggest that the
      differences observed between hypertensives and normotensive subjects can be
      accounted for by PKC activation and insulin exposure.

PMID- 9162440
TI  - Salt sensitivity and insulin resistance: Is there a link?
AB  - Salt sensitivity is not only found in patients with essential hypertension but
      also in normotensive individuals. These salt-sensitive normotensives are believed
      to be genetically predisposed to the development of hypertension. In this paper
      we present data from our studies in such normotensive salt-sensitive individuals,
      thereby focusing on the relationship between salt sensitivity and familial
      history of hypertension and on insulin sensitivity. Salt-sensitivity was
      associated with a positive familial history of hypertension, a finding that
      supports the hypothesis that salt sensitivity in normotensive individuals points
      to a genetic predisposition for the development of hypertension. Also, salt
      sensitive subjects displayed a hyperinsulinaemic response to an oral glucose load
      and a decreased insulin-mediated glucose disposal, as assessed by the insulin
      suppression test. The latter finding implies that insulin resistance is present
      in otherwise healthy, hypertension-prone individuals before overt hypertension
      develops. Assuming that there is a pathophysiological relationship between
      insulin resistance and salt sensitivity, our findings suggest that early
      recognition of insulin resistance and the implementation of measures aimed at
      improving insulin sensitivity could contribute to the prevention of
      cardiovascular disease in these individuals.

PMID- 9162441
TI  - Does insulin have a role in hypertension?
AB  - There is a growing body of evidence linking insulin resistance and
      hyperinsulinaemia with hypertension. Vascular delivery of insulin and glucose to
      the striated muscle may be rate-limiting for them to exercise their effects. We
      therefore studied the effects of experimentally induced hypertension
      (renovascular and DOCA-salt) on muscle uptake of [(3)H]-deoxyglucose ([(3)H]
      DOG)(non-metabolized glucose analog). In both models of induced hypertension
      uptake of [(3)H]-DOG was compared with the corresponding normotensive controls.
      Spontaneously hypertensive rats (SHR), however, had a reduced [(3)H]-DOG muscle
      uptake relative to normotensive WKY rats. To clarify a pro-hypertensive role on
      insulin it was administered by means of a sustained release subcutaneous implant
      to normotensive rats for 2 months and we could not detect hypertension in the
      resting state, though a transient hypertensive response to acute saline loading
      was present. On the other hand, young SHR made hyperinsulinaemic by the same
      method had an accelerated development of hypertension relative to control SHR.
      Thus it is not hypertension as such but the genetic susceptibility that is
      associated with insulin effects on blood pressure. In human hypertension we
      evaluated exercise (a maneuver known to improve insulin-sensitivity and reduce
      blood pressure) in non-obese essential hypertensive subjects. Three months of
      exercise training was associated with improved glucose tolerance and insulin
      clearance rate, but had no effect on 24-h ambulatory blood pressure. Thus, in
      essential hypertension insulin does not contribute significantly to the
      maintenance of hypertension. Taken together, our data indicate that hypertension
      does not cause insulin resistance and that exogenous hyperinsulinaemia does not
      produce hypertension in normotensive rats. However, in genetically determined
      hypertension insulin may play a role in its development.

PMID- 9162442
TI  - Ambulatory blood pressure and insulinaemia in different clinical conditions.
AB  - The aim of our study was to examine the relation between insulin and ambulatory
      blood pressure (ABPM) in several clinical conditions. ABPM monitoring was
      performed with Spacelabs device. Fasting plasma insulin (FPI) was measured by
      radioimmunoassay. In young, non-obese normotensive subjects (n = 32) there were
      correlations between FPI and both asleep (r = 0.61, p < 0.001), and awake
      systolic ABPM (r = 0.44, p < 0.01). We have not observed any significant
      correlation between FPI and ABP in borderline hypertensives or in patients with
      established hypertension. In a group of 21 hypertensive type 2 diabetics (age 52
      +/- 8 years) there was no significant correlation between FPI and ABPM. Among 14
      normotensive type 1 diabetics (age 31 +/- 7 years, diabetes duration > 10 years)
      there was a significant negative correlation between the daily dose of insulin
      and 24-h systolic ABPM (r =-0.63, p < 0.02). In 20 patients with renal failure on
      chronic haemodialysis we have found a significant negative correlation between
      FPI and 24-h systolic APBM (r = 0.80, p < 0.001) and 24-h diastolic ABPM (r = 
      0.55, p < 0.05). Similar negative correlations were found in 20 nondialysed
      subjects with moderate chronic renal failure. Taken together, our results suggest
      that insulin could reveal its hypertensive or vasodilatory effect which depends
      on a clinical condition of the studied subjects.

PMID- 9162443
TI  - Diabetes and hypertension: the scope of the problem.

PMID- 9162444
TI  - Hemodynamic and humoral correlates of insulin resistance in non-obese borderline
      hypertensives--a preliminary report.

PMID- 9162445
TI  - Smoking affects blood pressure.

PMID- 9162446
TI  - Smoking and blood pressure.

PMID- 9162447
TI  - How smoking affects blood pressure.
AB  - The addictive effects of smoking are only partly known, but it is likely that
      hemodynamic effects of tobacco smoking may contribute to the habituation. It has
      since long been known that blood pressure and heart rate increase during smoking.
      These effects are specifically associated with nicotine while the other
      components of which more than a thousand have been isolated seem to be of minor
      importance. The rise in blood pressure is due both to an increase in cardiac
      output and total peripheral vascular resistance. The blood pressure rise appears
      immediately and occurs before any increase in circulating catecholamines. In
      hypertensive patients the blood pressure lowering effect of beta-blockers may be
      partly abolished by tobacco smoking whereas alpha-receptor blockers seem to
      maintain the antihypertensive efficacy in smokers. It is a paradox that while
      smoking acutely increases blood pressure, a slightly lower blood pressure level
      has been found among smokers than nonsmokers in larger epidemiological studies.
      Because blood pressure may increase after cessation of smoking, a smoke quitting
      program should not postpone initiation of antihypertensive treatment in patients
      otherwise in need of such treatment.

PMID- 9162448
TI  - Salt sensitivity in hypertensive type-1 diabetes mellitus.
AB  - As sodium retention has been proposed as a causal factor in the development of
      hypertension in diabetic patients, a high incidence of salt sensitivity has been
      suggested. To evaluate the influence of dietary sodium intake on blood pressure,
      casual and 24-h blood pressure was measured in 30 hypertensive type-1 diabetic
      patients aged 24-67 (mean 46) years while they were on habitual diet, after 6
      days of low-sodium diet (50 mmol/day), and after 6 days of high-sodium diet (250
      mmol/day). Nine patients (30%) who increased their 24-h mean blood pressure by
      more than 10% when going from low- to high-sodium intake were classified as salt
      sensitive; the others as salt resistant. The salt sensitive group had a
      significantly lower urinary excretion of dopamine at baseline, and a higher
      diuresis and a more pronounced decrease in 24-h blood pressure during salt
      depletion (all p < 0.01). Low-sodium diet reduced casual and 24-h blood pressure
      by 4% in the total study population compared with 9% in the salt sensitive group
      (p < 0.01). There was no difference in glomerular filtration rate, filtration
      fraction, proteinuria or urinary sodium excretion between the groups.
      CONCLUSIONS: Sodium restriction more effectively reduces blood pressure in the
      salt sensitive minority of hypertensive type-1 diabetic patients irrespective of
      renal function. The incidence of salt sensitivity is not increased in
      hypertensive type-1 diabetic patients compared with essential hypertensive
      patients.

PMID- 9162450
TI  - [Subspecific classification of 11 clinical strains of Klebsiella pneumoniae based
      on their biochemical, antibiotic and plasmid profiles].
AB  - The paper summarizes at a subspecific level 11 clinical strains of K. pneumoniae.
      The objective of the work was to determine in a simple and effective way
      differences between different strains of the mentioned taxon. Biochemical
      characteristics, antibiogram and part of the plasmid spectrum were used for
      assessment of inter-species differences between different strains and at the same
      time their use as simple markers of epidemiological analyses is presented.

PMID- 9162449
TI  - [Occurrence of antibodies to chlamydial group antigens in the population of the
      Czech Republic].
AB  - A set of 4,178 human blood sera was tested including 3,093 samples collected from
      blood donors, 624 randomly collected samples. 124 samples collected from persons
      possibly exposed to Chlamydia infection, and 337 samples from patients of various
      hospitals in the districts of Brno, Olomouc and Rumburk. All the sera were
      examined using the complement fixation microtest and the antigen of Chlamydia
      psittaci for CFR (Bioveta, Ivanovice na Hane, CzR). Moreover, a subset of samples
      collected from selected groups (n = 209) was tested by CFR using the genus
      specific Ornithose-Antigen (Behring, Germany) (n = 209), another subset of 116
      samples by indirect immunofluorescence using the biological Chlamydia trachomatis
      Spot IF (Bio Merieux) (n = 116), and a subset of 224 samples by ELISA for the
      demonstration of IgG, IgM and IgA class of antibodies using the kit rELISA Medac.
      Complement fixing antibodies assayed with the Chlamydia psittaci antigen
      (Bioveta), reached titres of 1.5, 1:10 and 1:20 in 15.5%, 5.29% and 0.48% of the
      randomly collected samples, respectively. The corresponding values for the tests
      carried out with the Ornithose-Antigen were 1:10 in 10.9%, 1:20 in 8.9%, 1:40 in
      2.9% and 1:80 in 1.4%. ELISA yielded 52.7%, 26.85% and 17.59% positive results in
      the globulin classes IgG, IgA and IgM, respectively. Antibody titres from 1:20
      and from 1:10, determined with the Bioveta antigen, were found in 2.36% and 9.47%
      within a representative group of blood donors. The corresponding values for the
      group of the hospitalized patients were 14.54% and 24.93%, respectively, and for
      the group of persons possibly exposed to Chlamydia infection 2.42% and 8.87%
      respectively. The indirect immunofluorescence test yielded positive, negative ad
      doubtful results in 47.41%, 27.59% and 25.0% persons of the latter group. This
      group showed also a higher percentage (37.07%) of positive results in ELISA in
      the class IgA than the randomly selected persons.

PMID- 9162451
TI  - [Parvovirus B19 in the Czech Republic. Seroepidemiologic study].
AB  - Erythema infectiosum which is caused by parvovirus B 19 is notified in the Czech
      Republic similarly as some other viral exanthemas under the diagnosis "Other
      viral infections affecting the skin and mucosae, not listed elsewhere" (B08).
      Analysis of the epidemiological position in the Czech Republic in 1993-1995 was
      based on EPIDAT data, documentation of epidemic of 1993 in the Liberec district
      and serologically confirmed minor epidemics (1994, 1995). An increased number of
      cases (in particular in late winter and early spring) is observed in several
      years' (cca four-year) cycles and only in some districts. Children aged 3-10
      years (88.2%) are affected predominantly. All the year round however sporadic
      cases affecting people of all age groups are notified. Concurrent illness of
      several family members (usually two) was confirmed by laboratory tests only in 9
      of cca 200 investigated cases. The source of infection is usually not identified.
      The increase in the number of cases in a given locality rose rapidly after brief
      time intervals. The longest interval between two cases was 24 days. In families
      all affected members contracted the disease with 24 hours. According to the
      seroprevalence of the IgG parvovirus B 19 in different age groups the majority of
      cases in subadult and adult subjects is not diagnosed and notified.
      Seroprevalence of IgG antibodies of the parvovirus B 19 in subjects with
      arthropathies was 72.4%, in subjects with suspect borreliosis 69.9% an in the
      normal population cca 50%.

PMID- 9162452
TI  - [Detection of mycobacteria using the Bactec radiometry method and standard
      culture methods].
AB  - For parallel detection of mycobacteria by the radiometric method using a Bactec
      460 TB apparatus and by the standard cultivation method 5383 specimens of
      pathological material from patients of in-patient TB departments (90%) and other
      health facilities (10%) were examined. 492 samples were positive. By the
      radiometric method alone 114 samples were positive and by cultivation only 15
      samples. The mean period of detection was 12.9 days for the Bactec method, for
      the cultivation method 32.4 days. For the Bactec system 0.4 ml inoculum was used
      and one cultivation vessel, for the cultivation 0.4-0.6 ml inoculum and two egg
      media per sample. Of 15 samples positive on cultivation only, rarely colonies
      were obtained after 6-9 weeks' incubation.

PMID- 9162453
TI  - [Diagnosis of Lyme borreliosis with western blotting].
AB  - Spirochetes Borrelia burgdorferi sensu lato, selected as antigens for Western
      blot analyses were isolated from cerebrospinal (strain 192 M) and from blood
      (strain Kc90) and identified by means of monoclonal antibodies and the polymerase
      chain reaction (PCR) as B. garinii and B. afzelii. Differences between B. garinii
      and B. afzelii are in the genotype of the surface protein OspA and OspB, internal
      flagellin (Fla II) and the main extracellular protein (MEP). The reaction of
      polyclonal antibodies in 918 serum specimens and 180 specimens of cerebrospinal
      fluid was investigated in IgG and IgM immunoblots in patients with neurological
      symptoms, arthritis and skin manifestations suspect of Lyme borreliosis.
      Confirmation of the immunoenzyme ELISA reaction by means of immunoblots in the
      acute stage of borreliosis, in clinically obscure cases, in herpetic infection,
      mononucleosis and leptospirosis revealed a higher sensitivity and specificity of
      Western blot. Proteins of B. garinii with a molecular weight of 94, 84, 66, 60,
      56, 41, 39, 33, 29, 22, 18 and 14 kDa were detected in the reaction with
      monoclonal antibodies and immunoglobulins of patients suffering from barreliosis.
      The frequency and intensity of the reaction of these antigens differed markedly
      in sera of patients suffering from borreliosis and sera of patients who suffered
      from a different infection. The external surface antigen OspA, OspB, OspC and
      protein with 39 kDA are significant markers of borreliosis. The most frequently
      detected antigens in cross reactions with immunoglobulins against other pathogens
      are proteins P66, P60, P41 which are dominant immunogens of all types of
      borrelias and moreover a humoral response to them develops in the acute stage of
      the disease. In arthritis and neuroborreliosis a different in IgG immunoblots was
      found.

PMID- 9162454
TI  - [Encephalitozoon cuniculi--clinical and epidemiologic significance. Results of a
      preliminary serologic study in humans].
AB  - Recently attention in human medicine has been drawn to encephalitozoonoses.
      Increased liability to develop the infection is found in particular in people
      with an impaired immunobiological condition. Evidence of this are more numerous
      infections in AIDS patients. However, the impact of encephalitozoonoses cannot be
      ruled out in other groups of patients. This calls however for specific aimed
      investigations. The authors examined 98 sera of employees of a slaughterhouse for
      encephalitozoonosis. Five sera (5.1%) were positive. Sera of 92 forestry workers,
      22 dog breeders and 150 blood donors were negative. In future it will be
      necessary to focus attention on seropositive subjects in conjunction with the
      possible transmission of the disease from animals to man.

PMID- 9162455
TI  - [Serologic overview of rotavirus antibodies in children under 2 years of age].
AB  - A serological investigation in 120 children under two years confirmed the
      elevated prevalence of rotavirus antibodies after the age of nine months. In
      children above one year antibodies were detected in 30%. The results are
      consistent with those of similar studies where different laboratory methods were
      used.

PMID- 9162456
TI  - [Preliminary identification of Borrelia burgdorferi isolated from Ixodes ricinus
      ticks in eastern Slovakia].
AB  - The first finding of spirochetes Borrelia burgdorferi sensu lato in eastern
      Slovakia pertains to ticks Ixodes ricinus collected in the Kosice park forest in
      September 1995. The authors tested 7 strains using immunoblotting with 4
      monoclonal antibodies (Mab): H9724--specific to the genus Borrelia, identifying
      41 kDa flagellar protein, H5332--specific to OspA protein of B. burgdorferi, J
      8.3 and I 17.3 specific to OspA and OspB proteins of B. afzelii. All the strains
      belong to the genus Borrelia (reacted with Mab H9724), 6 of 7 strains designated
      Ir103, Ir105, Ir107, Ir108, Ir112 and Ir113 were identified as B. burgdorferi
      sensu lato (reacted with Mab H5332). None of the strains reacted with Mab
      specific for B. afzelii.

PMID- 9162457
TI  - [Toxocara infections in childhood in relation to reactive arthritis].
AB  - Reactive arthritis belongs to a group of rheumatoid diseases known as
      seronegative spondylarthritis or spondarthropathies. Of many reactive arthritis
      evoking agents, the authors focused on larval toxocarosis. The authors describe a
      child with high anti-Toxocara antibody and circulating antigen titres in
      combination with acute Chlamydia infection, which may have caused reactive
      arthritis in this immunologically impaired organism. This is evidence of the
      coincidence of different pathological factors manifested by reactive affection of
      the knee joint.

PMID- 9162458
TI  - [Tuberculosis of the respiratory system--clinical picture].
AB  - Analysis of the clinical development of tuberculosis in 100 patients admitted in
      1995 to the Clinic of Pneumology and Thoracic Surgery of the 3rd Medical Faculty
      Charles University is focused on the pitfalls of correct diagnosis and treatment.
      The development of the disease is influenced by a number of risk factors and
      serious associated diseases. Proper verification of TB is emphasized: in addition
      to laboratory methods also the surgical approach with histological confirmation
      holds its place. Antituberculotic treatment according to recommended regimens
      calls in indicated cases of drug intolerance for pharmacokinetic examination.
      Tuberculosis is a disease which requires a multidisciplinary approach.

PMID- 9162459
TI  - [Detection of DNA specific for Mycobacterium tuberculosis in archeological
      material using the polymerase chain reaction].
AB  - The paleopathological diagnosis of bone tuberculosis in archeological findings
      may be confirmed by the polymerase chain reaction (PCR). If the M. tuberculosis
      specific DNA fragment is amplified, then the presence of this microorganism in
      the sample is demonstrated. The pilot study presented investigated whether our
      molecular biology laboratory can collaborate with anthropologists in
      paleopathological analyses and to verify the use of the commercial diagnostic kit
      Cleanmix (Talent, Italy), for DNA isolation from archeological samples. The
      results were compared with the conclusions of anthropologists. Successful
      amplification of specific DNA fragments was achieved in a specimen from the
      period of the 13th to 15th century. The specimen consists of four thoracic
      vertebrae modified by osseous tuberculosis (gibbus). The PCR result was also
      positive in a five-year-old femur sample of a patient with chronic pulmonary
      tuberculosis. All other specimens of various ages but without macroscopic
      symptoms of osseous tuberculosis, were PCR negative. These results suggest that
      it is possible to detect former infections with pathogenic microorganisms in
      archeological bones find.

PMID- 9162460
TI  - [New methodological approaches to the study and assessment of health status in
      occupational medicine].
AB  - The authors present materials on work conditions and workers' health state, that
      necessitate urgent measures to increase living standards, to meet sanitary and
      hygienic demands, to preserve health through alternative methods (time-related
      defence, early rehabilitation), to set strict economic penalties for employers'
      higher concern for better work conditions. The topics discussed include
      consideration of complex hazards (effects of chemicals coming from various media,
      influence of occupational and household physical factors) in setting an Allowable
      Daily Dose. Regional peculiarities should be taken into account in hygienic
      standardization.

PMID- 9162462
TI  - [The late sequelae of exposure to solvents (the gonadotropic, embryotropic,
      mutagenic and gerontogenic actions)].
AB  - Experiments, clinical and hygienic research revealed multiple long-term effects
      caused by various chemical solvents. Systematic study covered the solvents'
      influence on reproductive function (gonads, fetus, descendants) and helped to set
      safety standards for putting some solvents into production. Individual solvents
      appeared to accelerate natural aging. Important notion is that up to date
      epidemiologic research incompletely covered relationship between changes of
      health state and quantitative parameters (active concentrations/doses) of
      chemical hazards.

PMID- 9162461
TI  - [The toxicological, hygienic and clinical aspects of the action of low levels of
      organic solvents].
AB  - The article presents experimental data showing that Average Shift Concentration
      (ASC) and Maximal Single Concentration (MSC) for some solvents
      (tetrachloromethane, tetrachloroethane, dimethylformamide, benzene) are expedient
      to be justified. Clinical and hygienic materials proved significant health
      parameters (nervous system, peripheral blood) and urine levels of main
      metabolites to depend on chlorbenzene and toluene concentrations influencing the
      workers. Having analyzed the results, the authors recommended following hygienic
      norms in the air of workplace: for chlorbenzene ASC--50 mg/cu m, MSC--100 mg/cu
      m; biologic MAC for urine 4-chlorcatechol--0.05 g/l; for toluene ASC--50 mg/cu m,
      MSC--150 mg/cu m; biologic MAC for urine hippuric acid--1.5 g/l. The article
      shows some features of ASC and MSC practical application.

PMID- 9162463
TI  - [The effect of organic solvents on the child-bearing function of women painters
      (an epidemiological hygiene study].
AB  - Female painters, if compared to the reference group, appeared to have
      significantly higher incidence of pregnancy complications, spontaneous abortions
      and dead births. The painters' children were characterized by higher occurrence
      of respiratory cardiovascular and skin diseases, is the reference group.
      Incidence of congenital abnormalities was the same in both groups, but mothers
      exposed to organic solvents at work had children with congenital abnormalities of
      cardiovascular and central nervous systems, multiple defects and chromosomal
      aberrations, that were absent or less frequent in the reference group.

PMID- 9162464
TI  - [Occupational bronchial asthma due to organic solvents].
AB  - Thorough clinical, allergologic and immunologic examination of 65 patients who
      worked as building painters in contact with organic solvents proved these agents,
      not being allergens, to contribute in formation of occupational bronchial asthma.
      This type of bronchial asthma is characterized by some clinical features and
      pathogenetic mechanisms. A complex of clinical, allergologic and immunologic
      methods was elaborated to diagnose this type of bronchial asthma.

PMID- 9162466
TI  - [The control of the level of nitrogen oxides in the air of mines when using
      diesel-drive machines].
AB  - Laboratory and occupational studies evaluated up-to-date methods determining
      nitrogen oxides in atmosphere of mines. The authors elaborated new methods
      assessing nitrogen oxides in the air and suggested some improvements of the
      present techniques in accordance with specific conditions of mines. A novelty is
      a correction coefficient for assessment of nitrogen oxides through express method
      (indicator tubes).

PMID- 9162465
TI  - [The immunomodulating effect of noise (a review of the literature)].

PMID- 9162467
TI  - [Industrial ecology problems in the activities of the State Epidemiological
      Health Surveillance Center in Shchelkovo District, Moscow Province].
AB  - Thorough work of specialists in occupational hygiene and environment protection
      enables State Sanitary and Epidemiologic Supervision Departments to better work
      conditions substantially and to lower harm to environment and public health.
      State Sanitary and Epidemiologic Supervision Department in Shchelkovo [correction
      of Shyolkovo] accomplished cessation of some industrial processes polluting
      environment, resettlement of inhabitants away from expanded zones of sanitary
      protection, important measures in industrial ecology.

PMID- 9162468
TI  - [The etiology and pathogenesis of chronic gastritis in flight personnel].

PMID- 9162469
TI  - [The clinico-pathogenetic aspects of chronic exposure to organic solvents].
AB  - Retrospective and prospective epidemiologic studies revealed features of
      pathomorphosis and response, defined various pathogenetic mechanisms induced by
      complex, combined exposure to poisons at work. The article determined main
      neurologic and hematologic syndromes considered as early and sensitive diagnostic
      criteria of poisons influence on workers exposed to them. The authors described
      some variants of course and long-term complications of prolonged exposure to
      poisons.

PMID- 9162470
TI  - [The pathogenesis, clinical picture and treatment of poisonings by organic
      solvents, derivatives of chlorinated hydrocarbons (trichloroethylene, carbon
      tetrachloride)].
AB  - Clinical studies and experiments on laboratory animals covered mechanism of
      trichloroethylene toxicity. The chemical and its metabolites cause nonspecific
      toxic effects in membranes and therefore induce energy metabolism disorder that
      is proved to be a trigger of pathologic process in the intoxication. Experimental
      studies failed to disclose and explain mechanism of compromised calcium
      metabolism and its role in cardiac manifestations seen in trichloroethylene
      poisoning.

PMID- 9162471
TI  - Phylogenetic analysis.

PMID- 9162472
TI  - Drosophila development: a receptor for ommatidial recruitment.
AB  - Recent work shows that the differentiation of all the cell types found in the
      compound eye of Drosophila melanogaster is induced by reiterative activation of
      the EGF receptor.

PMID- 9162473
TI  - AIDS: decline and fall of immune surveillance?
AB  - Recent observations cast doubt on the view that cytotoxic T cells play a key role
      in keeping HIV-1 infection in check, and that it is the decline in this mechanism
      of immune surveillance that permits progression to AIDS.

PMID- 9162474
TI  - Synaptic plasticity: a role for nitric oxide in LTP.
AB  - Nitric oxide is back in the spotlight with a new series of studies showing that
      it plays an important role in long-term potentiation, the best-studied type of
      synaptic plasticity in the central nervous system thought likely to play an
      important role in learning and memory.

PMID- 9162475
TI  - Tumor suppressors: a developing role for p53?
AB  - An increasing body of evidence indicates that p53, the product of a tumour
      suppressor gene, has a role in development - could this developmental role have
      provided the primary driving force in the evolution of a protein best known as a
      stress-response integrator?

PMID- 9162476
TI  - Cell migration: don't tread on me.
AB  - During directed cell migration, telling cells to avoid certain areas may be as
      important as attracting them to others. The recently identified wunen gene is
      involved in the repulsive guidance of migrating primordial germ cells in
      Drosophila.

PMID- 9162477
TI  - Structure prediction: folding proteins by pattern recognition.
AB  - Although we are still a long way from being able to predict the details of
      protein structure from the underlying chemistry, slow but steady progress is
      being made at modeling structural features by recognizing the patterns that
      connect sequence to structure.

PMID- 9162478
TI  - Germinal centers: a second childhood for lymphocytes.
AB  - Recent observations show that, in the peripheral lymphoid organs known as
      germinal centers, lymphocytes appear to regain the phenotypic and molecular
      traits of immature cells; this cellular regression may play an important role in
      the affinity maturation of immune responses.

PMID- 9162479
TI  - Nematode development: evolutionary detours of a pivotal cell.
AB  - The anchor cell plays a central role in organizing the reproductive structures of
      the nematode Caenorhabditis elegans. Recent studies show that significant
      alterations in the origin, function and fate of this key regulatory cell have
      occurred during the course of nematode evolution.

PMID- 9162480
TI  - Cell motility: complex dynamics at the leading edge.
AB  - The intracellular pathogen Listeria monocytogenes is a useful model for general
      actin-based cell motility, because it recruits host actin and associated proteins
      for movement. Recent data have shown that these associated proteins include the
      Ena/VASP family of proteins and the actin-related proteins Arp2 and Arp3.

PMID- 9162481
TI  - Neural development: instructions for neural diversity.
AB  - Extracellular signals that can influence the fate of multipotent progenitor cells
      have been described in recent studies of the vertebrate nervous system,
      emphasizing the contribution of instructive mechanisms to the generation of
      cellular diversity.

PMID- 9162482
TI  - Cholesterol homeostasis: clipping out a slippery regulator.
AB  - SREBPs are transcriptional activators central to cholesterol homeostasis. Recent
      work has shown that a two-step cleavage of membrane-bound SREBPs frees them to
      enter the nucleus. An activator of the first, sterol-regulated proteolysis step
      has also been identified.

PMID- 9162483
TI  - Signalling pathways: a common theme in plants and animals?
AB  - The unexpected notion that disease resistance mechanisms may use similar
      regulatory pathways to developmental processes has emerged from recent advances
      in understanding signal transduction pathways in insects, mammals and plants.

PMID- 9162484
TI  - Ribosomes: protein synthesis in slow motion.
AB  - Using image reconstruction methods, electron microscopists can now visualize
      ribosomes at resolutions so high that the changes in the positions of ribosome
      bound tRNAs which occur during protein synthesis can be seen.

PMID- 9162485
TI  - Imaging techniques: picture the world with kaleidoscope dyes.
AB  - Advances in fluorescence light microscopy have facilitated the production of
      images from multiply labeled specimens.

PMID- 9162487
TI  - My word. Money isn't everything.

PMID- 9162488
TI  - Political science.

PMID- 9162489
TI  - The lab home page.

PMID- 9162491
TI  - Medline.

PMID- 9162490
TI  - Cell-free expression of a GFP fusion protein allows quantitation in vitro and in
      vivo.

PMID- 9162492
TI  - Visual psychophysics.

PMID- 9162486
TI  - Limb morphogenesis: connections between patterning and growth.
AB  - Limb development is a complex process involving precise control of both
      patterning and growth. Great strides have been made in understanding limb
      morphogenesis and identifying essential patterning genes in Drosophila.
      Differential expression of these genes divides the future limb into territories,
      which will give rise to different regions of the adult appendage. Recent analyses
      have defined the role of territorial boundaries as organizers of both patterning
      and growth, highlighting the connection between these two processes. The
      organizing activity of territorial boundaries seems to be mediated through the
      activity of two locally produced morphogens: Wingless and Decapentaplegic. We
      propose a model in which these two molecules, distributed in a graded fashion,
      act in synergy to promote growth of the entire appendage. We also suggest that
      existence of growth inhibitors that counteract the action of Wingless and
      Decapentaplegic; by opposing the gradient of these growth factors, the inhibitors
      guide the near-uniform proliferation that shapes the imaginal discs from which
      the adult appendages are formed in Drosophila.

PMID- 9162493
TI  - Embryonic asymmetry: left TGFbeta at the right time?
AB  - Vertebrates have consistent differences between their left and right sides. In
      all species, nodal, a transforming growth factor beta superfamily signalling
      protein, is involved in a late step in the pathways that specify such asymmetry
      in the embryo. Earlier components seem not so well conserved.

PMID- 9162495
TI  - Lymphocyte homing: the scent of a follicle.
AB  - The recent discovery of a receptor needed for lymphocyte migration into lymphoid
      follicles indicates that multiple chemoattractive gradients allow lymphocytes to
      navigate to specialized niches in lymphoid organs.

PMID- 9162494
TI  - Drosophila development. Delimiting patterns by repression.
AB  - Patterning of the Drosophila embryo requires not only the proper activation of
      determinants at specific times, but also their restriction to specific places.
      Recent studies on transcriptional repressors show how they delimit the gene
      expression patterns to ensure normal development.

PMID- 9162496
TI  - Nodulation: finding the lost common denominator.
AB  - The products of the 'common' nodulation genes of Rhizobium catalyze the synthesis
      of signal molecules and were once thought to have similar functions in all
      Rhizobium species; subtle differences in the activities of these gene products
      have now been discovered that influence the host range of Rhizobium species.

PMID- 9162497
TI  - Dosage compensation: X-repress yourself.
AB  - Dosage compensation in Caenorhabditis elegans involves the sex-specific
      recruitment to the X chromosome of a protein complex, the nature of which
      suggests that there are mechanistic links between chromosome segregation and
      global transcriptional regulation.

PMID- 9162498
TI  - Cortical development: layers of complexity.
AB  - Studies of spontaneous mutant mice with neurological phenotypes, particularly the
      cloning and analysis of the genes responsible, are shedding light on the complex
      processes that lead to formation of the deceptively simple layered structure of
      the cerebral cortex.

PMID- 9162499
TI  - Vesicle traffic: get your coat!
AB  - The budding of transport vesicles from the Golgi complex is initiated by
      activation of the small GTPase ARF; the discovery of enzymes that can convert
      soluble ARF-GDP to the active, membrane-associated form ARF-GTP will shed light
      on the mechanism and regulation of the formation of transport vesicles.

PMID- 9162500
TI  - Morphogenesis: FGF branches out.
AB  - Signalling via tissue-specific receptors for fibroblast growth factor is
      important in tracheal branching and mesodermal patterning in Drosophila; both
      processes may involve a common primary response - detachment and directed
      migration of the target cells - that is conserved from worms to mammals.

PMID- 9162501
TI  - T-cell subsets: recruiting the right kind of help.
AB  - The qualitative features of immune responses are influenced by the polarization
      of helper T cells towards two distinct phenotypes, Th1 and Th2. Recent evidence
      suggests that these helper cell subsets may be differentially recruited to the
      sites of different types of inflammatory reaction.

PMID- 9162502
TI  - Transposable elements: how non-LTR retrotransposons do it.
AB  - The source of the enzyme activity responsible for the transposition of
      retrotransposons of the type that lack terminal repeats has at last been
      identified: in L1Hs elements, it is encoded by the second open reading frame and
      is a nuclease related to the apurinic repair endonucleases.

PMID- 9162503
TI  - Perceptual learning: insight in sight.
AB  - The Hebbian synapse and Hebb learning rule are familiar to those working on
      biological and machine learning. But Hebb's insights from over fifty years ago
      carry many other lessons in learning and may contribute to a more parsimonious
      taxonomy of the mechanisms involved.

PMID- 9162504
TI  - DNA-protein interactions: IHF--the master bender.
AB  - The crystal structure of Escherichia coli integration host factor complexed with
      DNA reveals how the sequence-specificity of DNA binding can be determined almost
      entirely by the structural features of the DNA itself and not by direct readout
      of the base sequence. There are lessons to be drawn for other DNA-binding motifs.

PMID- 9162505
TI  - Autoimmunity: when self-tolerance breaks down.
AB  - The spontaneous development of destructive polyarthritis in mice transgenic for
      an autoreactive T-cell receptor supports the notion that a failure of T-cell self
      tolerance can lead to similar diseases in humans, and sheds new light on the role
      of peripheral tolerance in the avoidance of such pathological immune responses.

PMID- 9162507
TI  - [Diagnostic strategy for a solitary thyroid nodule. Example of development of
      recommendations for a practice guideline].
AB  - The solitary thyroid nodule is frequently observed and many strategies are
      proposed for the diagnosis of the etiology and for the choice of treatment.
      Despite many discussions no clear consensus has been so far reached. The french
      groups concerned by this problem set up a Clinical Practice Guide line with the
      methodological help of Agence Nationale pour le Developpement de l'Evaluation
      Medicale. Based upon the critical review of the literature a consensus was
      obtained concerning the natural history of the nodules and the diagnosis value of
      the complementary explorations. The clinical approach alone completed by a TSH
      determination gives the therapeutical choice in about 30% of the patient without
      any other explorations. In the remaining cases 3 methods (isotope scan,
      echography, cytopuncture) can be used alone or in a combined sequence. So far no
      strategy can be privilegiated. It is necessary to set up a systematic comparison
      between the possible strategies and this will be made by the french thyroid
      specialists after this first step of delimitation of a clinical practise guide
      line.

PMID- 9162506
TI  - Cell cycle: routine role for Ras.
AB  - The Ras proteins are key mediators of the early cellular response to mitogens;
      the way in which they influence the later events in the cell cycle is beginning
      to fall into place.

PMID- 9162508
TI  - [Laboratory for exploration of small vessels: its utility in vascular diseases].
AB  - Small vessel investigative laboratories for the in vivo study of the human
      microcirculation are few. Everyone believes that the combination of clinical
      examination. Doppler scanning and radiology ensures thorough investigation of
      peripheral vascular diseases. Capillaroscopy, plethysmography, oximetry,
      thermography, laser-Doppler, volumetry, and measurement of ambulatory venous
      pressure are rarely used for these diseases in routine practice, because they are
      often considered expensive, time consuming, inaccurate and eventually without
      practical consequences for patients. The aim of the present study is to summarize
      the 20-year-experience of such a small vessel laboratory, and to demonstrate its
      usefulness, both in research and in the routine practice of Vascular Medicine.
      Raynaud's phenomenon, critical ischemia, and chronic venous insufficiency will
      serve as examples for this demonstration.

PMID- 9162509
TI  - [Importance of the evaluation of food consumption in the risk of exceeding the
      permissible daily doses for poisons potentially contained in food].
AB  - The Codex Alimentarius in its General Principles committee proposes the
      definitions of risk assessment and risk management linked to ingestion of food
      additives and food contaminants. Moreover, three European directives imply for
      all member states an evaluation of food additives intakes by general population
      and by possible "at risk groups of consumers". This work is conducted in the
      general case of European Scientific Cooperation and is coordinated by United
      Kingdom. This paper describes the French approach, using a step-by-step procedure
      to evaluate food additives consumption. It emphasizes the importance of
      scientific works in this field of research to obtain french datas about french
      consumptions.

PMID- 9162511
TI  - [Introduction: soil pollution, agriculture and public health].

PMID- 9162510
TI  - [Hodgkin's disease trials conducted by the European Organization of Research and
      Treatment of Cancer (EORTC): their impact on the progress of cancerology].
AB  - Hodgkin's disease is a rare event that allowed key progress in the field of
      Oncology. Starting 1964 the EORTC has conducted a series of comprehensive
      controlled trials of outmost importance from the time of the first cures achieved
      with extended field radiotherapy until the observation that dose-response
      relationships could occur both for tumor control and for the incidence of second
      leukemia, cardiac, and pulmonary toxicities. Each of these steps is depicted in
      some detail. The contributions of the EORTC include in particular the first
      demonstration ever of the positive impact of an adjuvant chemotherapy on the
      freedom from progression and overall survival of a cancer (1964-1972), the
      identification of prognostic factors usable to adapt the aggressivity of
      treatment to patient's risks and the role of excess mortality from iatrogenic
      origin. Directions are indicated to insure a continuous progress to the Oncology
      field through additional Hodgkin's disease studies.

PMID- 9162512
TI  - [Degradation of soil quality: health and environmental risks].
AB  - This is a general survey of soil quality degradation and its consequences on
      human health and environment quality. The first part deals with the large
      complexity and reactivity of soil and its specific position as an environmental
      interface. The origin and behaviour of the main pollutant accumulated in soils
      are treated in the second and third parts. A special attention is paid to the
      main pollutants i.e., anions, cations (trace elements), pesticides, persistent
      organic pollutants (POP), bacteria, DNA... As they are closely linked to the soil
      constituents (clays, humus...), their real toxicity or effectiveness is examined.
      In the last part, the risks of soil pollutants for the environment and human
      health are shortly considered. Direct risks for health are few and mainly concern
      the ingestion of polluted soil by children; as regards the ecotoxicological and
      toxicological risks, the Critical pollutant loads have to be defined. The main
      risks are indirect and involve pollution of either the food chain or of the water
      and sediments by vertical or lateral (erosion) transfers.

PMID- 9162513
TI  - [Treatment of sludge from purification stations with the purpose of ameliorating
      soils intended for agriculture: parasitic contamination and model development
      with a view to managing the sanitation risk].
AB  - Helminth eggs (Ascaris, Taenia...) present in urban sludge constitute a sanitary
      risk when used for the enrichment of agricultural soil. These eggs are very
      resistant in the environment and their survival could reach 6 months to one year
      in soils. To control the risks for the public health, we have to determine
      parameters leading to the eggs destruction in soils. Then the aim of the work is
      to study several conditions (humidity, temperature, texture,...) that could
      influence the survival of intestinal nematode eggs in various types of soil.
      Survival experiments were carried out in clayey soil, silty-loam soil and sandy
      soils with humidity levels corresponding to: field capacities, wilting point and
      variation between this 2 limit point (storage temperatures 4 degrees C, 19
      degrees C and 30 degrees C). The result of this study has shown that the
      temperature conditioned for a great part the survival of the eggs in all types of
      soils with survival times superior at two year with a temperature of 4 degrees C.
      Between survivals at 20 degrees C and 30 degrees C, no difference has been
      observed. The humidity is the second parameter that condition the egg survival
      with a good viability preservation at the wilting point. This study also shows
      better survival in the conditions of deep soil with the protection of the egg
      from drying. With these data and with the simulation of continental temperate
      conditions, a contamination rate of 0.35% could be found on the surface soil
      after one year and a more important rate in the deep soil with 10.6%. The last
      step is the validation of this model and calculated values seem to be a good
      evaluation of the results found on fields. All these data must be take into
      account for the establishment of the regulation about the urban sludge reused for
      agricultural purpose.

PMID- 9162514
TI  - [Effects of heavy metals on snail development. Use of snails as bio-indicators of
      heavy metal pollution for the preservation of human health].
AB  - The use of snails as biological indicators is particularly appropriate for
      metals, which they accumulate in their organs. The aim of the present experiment
      was to carry out a rigorous experimentation in the laboratory and in the wild in
      order to develop a methodology for the use of snails at a known stage of growth
      that would give precise information on the toxicity of heavy metals for different
      concentrations and durations of exposure. We have developed a test of toxicity
      based on the effects of a noxious and carcinogenic element, cadmium, on the land
      snail Helix aspersa aspersa (H.a.a) of one month of age. Five concentrations (50
      to 800 micrograms/g), were selected to estimate the concentrations causing 50%
      inhibition of growth (EC 50) at 14 days: 190 micrograms/g and at 28 days: 180
      micrograms/g. A soil matrix contaminated with metals (soil including 800
      micrograms/g Cr, 20 micrograms/g Cd, 800 micrograms/g Pb and 2000 micrograms/g
      Zn) was incorporated into the food at 50 and 75%, it too inhibited the growth of
      juvenile snails compared to incorporation of control soil. An accurate and rapid
      (2 to 4 weeks) method is therefore available for the evaluation of the toxicity
      of pollutants by ingestion. The first trials of this method in the wild consisted
      of placing batches of 2-month-old snails, identical to those used in the first
      lab tests, in locations that were either polluted or not. Differences in growth
      were observed depending on the locations; analysis of the levels of metal in the
      organs of the snails should enable us to check if there is a correlation between
      these levels and the growth rates. The results obtained with cadmium compared to
      those of other authors working with earthworms and soil arthropods show that
      snails give responses to concentrations comparable to those of earthworms and
      much more rapidly and with more sensitivity than those of collembolla for
      example. The ease of handling snails and the perfect control of their breeding
      are essential factors in carrying out reliable bioassays in toxicology and in
      ecotoxicology.

PMID- 9162515
TI  - [Video-assisted coronary artery bypass].
AB  - The benefits of the internal mammary artery (IMA), as a graft, particularly for
      the left anterior descending (LAD) coronary artery disease, have been
      demonstrated. Coronary artery bypass grafting (CABG) without cardiopulmonary
      bypass (CPB) is now an accepted technique of myocardial revascularization.
      Thoracoscopy and a minimal thoracotomy have been applied to cardiac surgery,
      however its use has not been well defined; in our approach, we harvested the left
      IMA thoracoscopically. Following this the left IMA-LAD coronary artery
      anastomosis was fashioned, by means of a left small anterior thoracotomy on the
      beating heart without CPB. A double lumen endotracheal tube was used so the lung
      could be collapsed. Three left lateral chest ports of 1 cm were made, and the
      thoracoscope was placed through the initial port, permitting inspection of the
      thorax. The other ports were used for IMA dissection, using endoscopic
      instruments (electrocautery, grasping, forceps,...), the side branches were
      controlled by either cautery or endoscopic clips. When it was possible, the
      anterior port was extended doing a small left anterior thoracotomy, the
      pericardium was exposed, the IMA was divided and exteriorized through the
      thoracotomy. After coronary artery control, the bypass graft was carried out on
      the beating heart without CPB, in 26 patients. From september 1995 to july 1996,
      we have operated on 30 patients using this technique. We believe that with
      increasing operator experience, this minimally invasive approach will have a
      major impact on the management of the coronary artery disease patients, with a
      faster recovery, shorter hospitalization, and certainly less cost.

PMID- 9162516
TI  - [Eulogy of Jacques Hepp (1905-1995)].

PMID- 9162517
TI  - [The return of diphtheria in Europe. Is the French population protected?].
AB  - Following the generalized vaccination of children, the European countries
      achieved the elimination of diphtheria. However the huge epidemic which rages
      since 1990 in the New Independent States of ex-URSS, culminating in 1994-1995
      (with respectively 47,802 and 50,412 notified cases), has showed that diphtheria
      could be still threatening. A serosurvey was carried out in France on 1,025 adult
      patients attending the emergency wards of three hospitals, located in different
      parts of this country. This study showed the insufficient immunity of adults, for
      lack of a routine programme for revaccination: only half of them have antibodies
      assuring their protection. The antitoxic immunity decreases according to age.
      This decline is more marked in women than in men, most of them being reimmunized
      during the military service. These data confirm the alarming results of similar
      serosurveys performed in others industrialized countries. The present risk of
      importing diphtheria in these countries requires a strengthening of clinical and
      bacteriological surveillance of all cases of infections attributable to C.
      diphtheriae, and could justify a revaccination programme for adult population,
      including a regular booster, at 10 year-interval, of a reduced dose of diphtheria
      toxoid (d), and/or using the combined toxoid Td in the wounded, instead of
      tetanus toxoid alone.

PMID- 9162518
TI  - 1996 IAIMS Symposium. Building infrastructure for integrated health systems.
      Proceedings. Nashville, Tennessee, September 27, 1996. Dedicated to Richard T.
      West.

PMID- 9162519
TI  - Interferon-tau and pregnancy.
AB  - A type I interferon known as IFN-tau is expressed massively by the outer
      epithelium (trophectoderm) of the preimplantation trophoblast of ruminant
      ungulate species, such as cattle and sheep, for a few days during early
      pregnancy. They signal to the mother that she is pregnant and indirectly prevent
      regression of the corpus luteum so that progesterone production is maintained and
      normal ovarian cyclicity avoided. Despite their clear roles as reproductive
      hormones, the IFN-tau have the typical antiviral, antiproliferative, and
      immunomodulatory activities of other type I IFN. They are most closely related to
      the 172 amino acid IFN-omega. Unlike other type I IFN, they are not virally
      inducible and appear to be produced constitutively as the trophectoderm first
      forms during the development of the blastocyst. The discovery of the IFN-tau
      illustrates the diverse activities of interferons and their likely involvement in
      the normal embryonic development of mammals. The diversity of mechanisms
      different groups of mammals use to prolong the functional life span of the corpus
      luteum in early pregnancy is probably the consequence of genetic conflict between
      the genes of the mother and her offspring, which has led to remarkably high rates
      of change in placental structure and trophoblast signaling mechanisms.

PMID- 9162520
TI  - Why do so many cancer patients fail to respond to interferon therapy?
AB  - Since their first use in the clinic some 25 years ago, interferons (IFNs) have
      become accepted therapy in a range of cancer forms. However, although in some
      patients they induce remission, in the great majority they are of no benefit or,
      at best, lead only to minor improvements. This review considers possible reasons
      for these failures.

PMID- 9162521
TI  - Recombinant Interferons beta and gamma have a higher antiviral activity than
      interferon-alpha in coxsackievirus B3-infected carrier state cultures of human
      myocardial fibroblasts.
AB  - We compared the antiviral activities of three recombinant human interferons (IFN
      alph2a, IFN-beta, and IFN-gamma) in cultured human myocardial fibroblasts to
      select a candidate for trial in heart disease induced by cardiotropic
      enterovirus, e.g., coxsackievirus B3 (CVB3). Cells were exposed to CVB3, and
      after 7 days, when a persistent infection had developed, IFN was added. Virus
      yields were measured on alternate days for the next 7 or 16 days, and IFN
      activity was assessed as the percentage reduction in yield. IFN-gamma and IFN
      beta were both highly active and reduced virus yields by 2 log (EC(99)) at
      concentrations of 23.4 IU/ml (SD = 8.6) and 10.1 IU/ml (SD = 3.2), respectively;
      with 250 IU/ml of either IFN, no infectious virus was formed. Unexpectedly, IFN
      alpha2a (EC(99)> 1250 IU/ml) was at least 120 times less active than IFN-beta;
      after use for 8 days or more, the minor effects it produced were no longer
      related to the concentration applied. Despite the pharmacokinetic advantages of
      IFN-alpha2a, our data suggest that IFN-beta should in preference be evaluated in
      the clinic.

PMID- 9162522
TI  - Regulation of interleukin-6 expression in porcine immune cells.
AB  - Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates the immune
      response, acute-phase reaction, and hematopoiesis. As a first step in studying
      the actions of IL-6 in pigs, the regulation of IL-6 expression was examined in
      various swine cells, including a fibroblast cell line, peripheral blood
      mononuclear cells (PBMC), and alveolar macrophages. IL-6 expression in
      transformed swine testicular (TST) fibroblasts was enhanced by TNF and IL-1 beta
      and to a lesser extent by poly(I).(C) and LPS. IL-6 was induced in porcine PBMC
      by either LPS or PHA; however, the combination of LPS plus PHA resulted in
      maximal IL-6 expression. Furthermore, in PBMC cells separated by adherence, LPS
      was a more potent inducer than PHA in adherent cells, whereas PHA was more potent
      in nonadherent cells. Alveolar macrophages collected from different pigs could be
      divided into low and high responders with respect to IL-6 induction by LPS. IL-6
      mRNA induction by LPS could be detected in only 6 of 20 donor animals. Other
      inflammatory cytokines (IL-8, IL-beta, and TNF) were readily induced by LPS in
      alveolar macrophages from both low and high responders. Treatment of low
      responder alveolar macrophages with conditioned medium containing IFN-gamma did
      not significantly alter the capacity of these macrophages to synthesize IL-6 mRNA
      in response to LPS. Comparison of IL-6 production capacity by the cell types in
      this study revealed the following order: PBMC = high-responder alveolar
      macrophages >> TST.cells > low-responder alveolar macrophages. Thus, PBMC appear
      to be quantitatively the most significant source of IL-6 in swine on a per cell
      basis.

PMID- 9162523
TI  - Enhancement in vivo of the antiinflammatory and antitumor activities of type I
      interferon by association with the synthetic immunomodulator murabutide.
AB  - The therapeutic efficacy of type I interferon (IFN) has been reported to vary
      considerably in different indications. The use of the cytokine as adjuvant
      therapy has been suggested to enhance its efficacy and reduce the toxicity
      frequently associated with long-term and high-dose administration. In this study,
      we have assessed the activity of type I IFN in the protection against and
      treatment of acute hepatitis induced in mice by the administration of
      concanavalin-A (ConA). At the same time, we have evaluated the efficacy of the
      synthetic immunomodulator murabutide when administered alone or in combination
      with type I IFN to protect against ConA hepatitis and in the treatment of tumors
      in MethA sarcoma-bearing mice. Our results demonstrate a prophylactic effect as
      well therapeutic effects of type I IFN and of murabutide in the inflammation
      mediated model of liver damage. The use of combination therapy presented enhanced
      efficacy in inhibiting the ConA-induced elevation of plasma transaminases. Both
      compounds were found to suppress IFN-gamma mRNA accumulation in the livers of
      ConA treated mice. This activity is discussed with respect to the mechanism of
      action of the two immunomodulators. In addition, the combination of murabutide
      with type I IFN exhibited synergistic antitumor activity that was clearly seen in
      the significant regression of MethA tumors and resulted in almost 50 percent
      tumor-free mice. The potential clinical application of combination therapies
      using a cytokine and a safe immunomodulator is analyzed in terms of enhancing the
      cytokine efficacy and extending its use to new indications.

PMID- 9162524
TI  - Activation of epidermal growth factor receptor tyrosine phosphorylation by tumor
      necrosis factor correlates with loss of cytotoxic activity.
AB  - TNF induces cytotoxicity in human tumor cells through a receptor-mediated process
      with unknown signaling characteristics. Evidence suggests that overexpression of
      transmembrane growth factor receptors with intrinsic tyrosine kinase activity may
      suppress the antiproliferative or cytotoxic activity of TNF, suggesting
      antagonism between these two signaling pathways in tumor cells. To investigate
      TNF cytotoxic signal transduction, ME-180 cervical carcinoma cell variants were
      isolated that expressed complete cytotoxic sensitivity (ME-180S) or resistance
      (ME-180R) to TNF but identical levels of p55 TNF receptor expression. ME-180R
      cells expressed threefold higher EGFR than the ME-180S cell line and TNF
      treatment stimulated EGFR tyrosine phosphorylation only in resistant cells.
      Activation of tyrosine phosphorylation in ME-180R cells was TNF concentration
      dependent and maximally stimulated (three- to-five-fold) after 10-15 minutes of
      treatment. Other tyrosine phosphoproteins were not affected by TNF incubation
      demonstrating specific TNF-stimulated tyrosine phosphomodulation of EGFR.
      Pretreatment with the tyrosine kinase inhibitor tryphostin before incubation with
      TNF resulted in partial reversal of TNF cytotoxic resistance in ME-180R cells and
      enhanced TNF responsiveness in ME-180S cells, suggesting a "protective" role for
      tyrosine phosphorylation in TNF-induced cytotoxicity. Together these results
      demonstrate that TNF-mediated tyrosine phosphorylation is differentially
      regulated in sensitive and resistant tumor cells and may play a critical role in
      the cytotoxic signaling process through differential expression or regulation of
      tyrosine protein kinases and phosphatases.

PMID- 9162525
TI  - Circulating interleukin-2 receptors are a group of multimeric proteins with
      immunoreactivity for interleukin-2 receptor alpha, beta, and gamma chains.
AB  - Soluble interleukin-2 receptor (sIL-2R) alpha chain serum levels as determined by
      enzyme-linked immunosorbant assay (ELISA) are commonly used to monitor various
      inflammatory and neoplastic disorders associated with lymphocytic proliferation
      and activation. The in vivo structure of this soluble receptor species, however,
      is not characterized. We investigated sera with elevated sIL-2R serum levels of
      patients with histologically proven cutaneous T cell lymphoma (CTCL) and high
      dose IL-2-treated melanoma patients and healthy donors. Purified recombinant IL
      2R alpha and beta chain molecules, produced by transfection of NIH/3T3
      fibroblasts and CHO cells, served as positive controls for purification and
      detection procedures. For selective enrichment of IL-2R molecules from
      supernatants and sera, affinity columns were prepared by coupling recombinant IL
      2 or monoclonal antibodies against the alpha and the beta chain of the IL-2R
      complex to cyanogen bromide-activated Sepharose. Western blotting with affinity
      purified fractions under reducing and nonreducing conditions revealed proteins
      that showed immunoreactivity for IL-2R alpha, beta, and gamma chain using several
      detection antibodies against these molecules. We conclude that the composition of
      sIL-2R in vivo is more complex than that of recombinant sIL-2R and can include
      all three IL-2R chains.

PMID- 9162526
TI  - Killing of Leishmania donovani amastigotes by poly ICLC in hamsters.
AB  - In vitro as well as in vivo studies suggest that cytokine-induced synthesis of
      nitric oxide (NO) from L-arginine is a major effector mechanism against
      intracellular pathogens. In this study, we demonstrate that golden hamsters
      infected with Leishmania donovani amastigotes upon treatment with polyinosinic
      polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly
      ICLC), a potent interferon inducer and immune enhancer, in combination with L
      arginine, develop the capacity to eliminate intracellular pathogens. This
      antileishmanial activity of poly ICLC was suppressed by N w nitro-L-arginine (N w
      NLA), an inhibitor of inducible NO synthase. Furthermore, prolonged treatment of
      infected animals with L-arginine alone for 5 days more after 5 day treatment with
      poly ICLC plus L-arginine increased the antileishmanial activity compared with 5
      day treatment with poly ICLC plus L-arginine, suggesting that inducible NO
      synthase, once activated, produces NO for 5 days more. Our results suggest that
      an L-arginine-dependent, NO-mediated mechanism is probably responsible for the
      antileishmanial action of poly ICLC.

PMID- 9162528
TI  - D-mannose dimer introduced human recombinant interleukin- 1 alpha, NEO IL-1
      alpha, exhibits altered tissue distribution in mice.
AB  - Previous studies have demonstrated that the carbohydrate-introduced recombinant
      human IL-l alpha exhibited impairment in both biologic activities in all the
      experiments in vitro and receptor binding capacity compared with intact IL-l
      alpha. However, the glycosylated IL-l alpha exhibited selective activities in
      vivo. In this study, we compared the tissue distribution of IL-l alpha and IL-l
      alpha coupled with D-Mana (l-6)Man [Man2 alpha) (l-6)IL-l alpha] in mice. Mice
      were injected by intravenous and intraperitoneal routes with 2.0 mu g
      radiolabeled IL-l alpha. At 1 and 2 h after IP injection, the level of Man2
      alpha) (l-6)IL-l alpha decreased twofold compared with that of IL-l alpha in
      kidney. In contrast, at 1 hour after administration, Man2 alpha) (l-6)IL-l alpha
      exhibited higher levels than IL-l alpha in blood, heart, and liver. No
      significant difference was observed in brain at each time point. IV injection
      demonstrated that Man2 alpha)(l-6)IL-l alpha decreased to approximately one-half
      the level of rhIL-l alpha in kidney. In contrast, Man(2 alpha) (l-6)IL-l alpha
      increased twofold over that of IL-l alpha in liver at 1 h after dosing. These
      findings are consistent with the result of IP injection. There was no significant
      difference between IL-l alpha and glycosylated IL-l alpha at 4 h after IV
      administration. These differences in tissue distribution may contribute to the
      selective activities of glycosylated IL-l alpha in vivo. The results also suggest
      that by coupling with mannose dimer, it is possible to develop neocytokines prone
      to liver distribution.

PMID- 9162527
TI  - In vivo and In vitro interferon induction in chickens by S -28828, an
      imidazoquinolinamine immunoenhancer.
AB  - Imiquimod and its analogs belonging to a class of imidazoquinolinamines, activate
      immune system via cytokine induction, and have antitumor and antiviral effects in
      mammals. In this study, we showed that a related analog, designated S-28828,
      induced interferon (IFN) and macrophage activating cytokine(s) (macrophage
      activating factor, MAF) in chickens in vivo, ex vivo, and in vitro. IFN and MAF
      were detectable in the serum of chickens following oral administration. Serum IFN
      levels were the highest at 2 h after treatment. Although there was no detectable
      IFN in sera of chickens at 8, 24, and 48 h after treatment, high levels of
      interferon inducible enzyme, 2'-5' oligoadenylate synthase (2'5'OAS) were present
      at these time points. In vitro and ex vivo studies showed that spleen cells, bone
      marrow (BM) cells, and peripheral blood leukocytes (PBL) were capable of
      producing IFN and MAF, although spleen cells produced the highest levels. Our
      results suggest that S-28828 administered orally may be a useful immunoenhancing
      and antiviral agent for chickens.

PMID- 9162529
TI  - [Study of HLA-II antigens in chronic hepatitis C and B and in acute hepatitis B].
AB  - The aim of this study was to analyze the variability of the HLA-II system in a
      series of patients with chronic hepatitis B, chronic hepatitis C and acute
      hepatitis B to know whether there is any relationship between the polymorphism of
      the HLA system, the different types of hepatitis and the evolution of the
      infection. HLA-II antigens were determined by a PCR technique in serum samples of
      24 controls, 22 cases of chronic hepatitis C, 38 cases of chronic hepatitis B and
      11 with acute hepatitis B. The prevalence of the HLA-DR4 antigen was lower in the
      cases of chronic hepatitis B (10.5%) and C (13.6%) than in the controls (33.3%),
      particularly the DRB1*0401 allele (p = NS). The prevalence of HLA-DR6 was similar
      in chronic hepatitis B (42.1%) and acute hepatitis B (45.5%). Predominance of the
      DRB1*1301 and DRB1*1302 alleles were, however, observed in acute hepatitis B
      (36.4%) versus chronic hepatitis B (13%). These data suggest that immunologic
      factors such as HLA antigens may influence in the susceptibility to infection by
      HBV and HCV. The use of PCR techniques which discriminate between the different
      alleles of the HLA antigens may provide better knowledge of the immune response.

PMID- 9162531
TI  - [Mechanical lithotripsy during retrograde cholangiography in choledocholithiasis
      untreatable by conventional endoscopic sphincterotomy].
AB  - Endoscopic papillotomy followed by the removal of stones with the Dormia basket
      is the treatment of choice in residual choledocolithiasis after cholecystectomy
      and in choledocolithiasis in patients with a high surgical risk. Nonetheless, the
      size of the stones may, occasionally, impede removal by this procedure.
      Mechanical lithotripsy may resolve this clinical situation. The authors present
      the results of this technique in 40 consecutive patients in whom the elimination
      of the stones was not possible by conventional methods and thus mechanical
      lithotripsy was performed. This procedure was found to be effective in 32 out of
      40 patients (80%). In 22 cases (55%) lithotripsy was effective in one session
      performed during the first ERCP, 8 (20%) required two procedures and in 2 (5%)
      three sessions were necessary. In 9 cases the stones were spontaneously
      eliminated with lavage using physiologic serum or diluted contrast, in 6 the
      stones were extracted by lithotripsy, in 16 they were eliminated by a
      conventional Dormia basket and in the remaining case the Fogarty balloon was
      used. Lithotripsy could not be carried out in 8 out of the 40 patients (20%) due
      to inability to pick the stone up in 7 cases and because of the impossibility of
      breaking the stone up with the lithotripsy basket in the remaining case. No
      complications directly related to lithotripsy were observed. In conclusion,
      mechanical lithotripsy in an effective and safe therapeutic alternative in large
      size choledocolithiasis and can be performed during endoscopy.

PMID- 9162530
TI  - [Treatment with endoscopic endoprosthesis in choledocholithiasis].
AB  - The results of the placement of endoscopic endoprosthesis in 51 patients with
      choledocholithiasis from October 1991 to December 1995 are reviewed. In 13 cases
      the endoprosthesis was provisionally placed. Surgical or endoscopic treatment was
      electively completed in all the cases. Thirty-eight patients received the
      endoprosthesis on a permanent basis. During the follow up (mean 15.2 months)
      extraction was completed and the prosthesis removed in three cases, one by
      emigration. Six patients presented recurrent biliary obstruction and underwent
      surgery or replacement of another prosthesis. In the latter cases, another two
      underwent surgery due to repeated obstructions. The remaining patients remained
      asymptomatic until the end of follow up or until death (8 cases) due to unrelated
      causes. Only three mild episodes of cholangitis were observed as complications
      related to prosthesis placement. The authors conclude that endoscopic
      endoprosthesis is an effective provisional treatment to solve acute situations
      and is a permanent alternative for unextracted choledocholithiasis following
      sphincterotomy in patients who cannot undergo other techniques and who have a
      short life expectancy.

PMID- 9162532
TI  - [Cholestasis associated with ticlopidine].
AB  - The case of a 56-years-old male with cholestasis associated with ticlopidine is
      presented. Cholestasis is an infrequent adverse effect of this drug. The patient
      was admitted to hospital because of jaundice, choluria, and itching of one month
      of evolution. The patient had taken ticlopidine twice a day for 3 months up to
      one week prior to admission for peripheral arteriopathy. Biopsy was performed
      showing acinar cholestasis and portal inflammatory infiltrate compatible with
      cholestasis due to hypersensitivity. Ticlopidine was discontinued by the patient
      himself one week prior to admission. The drug was not readministered and the
      evolution of the clinical and biochemical parameters of cholestasis decreased.
      The patient was asymptomatic and laboratory data were normal 4 months later.

PMID- 9162533
TI  - [Pyloric stenosis complicated by Wernicke-Korsakoff syndrome].
AB  - The Wernicke-Korsakoff syndrome (WKS) is a picture of oculomotor alterations,
      ataxia and confusion presented in chronic alcoholics. It has more rarely been
      described in non alcoholic patients with malnutrition. The case of a patient with
      ulcerous peptic disease of long evolution who consulted for a picture compatible
      with WKS following clinical manifestations of repeated vomiting secondary to
      complete pyloric stenosis is presented. The peculiarity of the picture and the
      convenience of prevention in malnourished patients receiving intravenous glucose
      sera is discussed.

PMID- 9162534
TI  - [A case of Sweet's syndrome associated with Crohn's disease].
AB  - The Sweet syndrome or acute febrile neutrophilic dermatosis is a well
      characterized cutaneous disease from a clinical and histological point of view
      and is frequently associated with systemic diseases. Prognosis is favorable with
      good response to corticoid therapy. A well documented case of Sweet syndrome
      associated with an outbreak of Crohn's disease with peculiar good therapeutic
      response is reported.

PMID- 9162535
TI  - [Recurrent rectorrhagia caused by angiodysplasia of the colon localized
      exclusively by scintigraphy with Tc-99m red blood cells].
AB  - A case of angiodysplasia of the colon with clinical manifestation of massive
      rectal bleeding is presented. The activity and the severity of the life
      threatening bleeding episode led to emergency exploratory laparotomy with
      intraoperative colonoscopy which was not diagnostic. Three years later, following
      multiple recurrent bleeding episodes and non diagnostic explorations, the
      localization of the hemorrhage was obtained by abdominal scintigraphy with 99mTc
      red blood cells. Surgical removal of the affected area achieved definitive cure.

PMID- 9162536
TI  - [Endoscopic ultrasonography: current and future perspectives].

PMID- 9162537
TI  - [Hyperaldosteronism, spironolactone and liver cirrhosis].

PMID- 9162538
TI  - [Cyclospora cayetanensis: a new enteropathogenic parasite].

PMID- 9162539
TI  - [Peripheral eosinophilia in ulcerative colitis: apropos of a case].

PMID- 9162540
TI  - [Cholestatic hepatitis associated with ticlopidine].

PMID- 9162541
TI  - [Acute hepatitis caused by diclofenac].

PMID- 9162542
TI  - [Hepatic toxicity caused by aceclofenac].

PMID- 9162543
TI  - [Tuberculous abscess of the pancreas as initial manifestation of AIDS].

PMID- 9162544
TI  - Carbohydrate digestion in sandflies: alpha-glucosidase activity in the midgut of
      Phlebotomus langeroni.
AB  - Midgut alpha-glucosidase (EC 3.2.1.20) activities were measured after ingestion
      of blood and sugar meals by the phlebotomine sandfly Phlebotomus langeroni. alpha
      Glucosidase activity increased significantly within 1 hr after a blood meal and
      was maintained at significantly high activities until 48 hr postfeeding, when it
      fell to basal activity levels. Midgut alpha-glucosidase activity also increased
      within 1 hr of feeding on a sucrose meal, but there was no discernable peak in
      activity during the days postingestion. Differences in the induction of enzyme
      activity after a sugar meal compared to a blood meal might reflect the mode of
      ingestion of the two types of meal. The sugar meal is released intermittently
      into the midgut from the crop, in contrast to the bloodmeal, which is directed
      into the midgut immediately after ingestion and digested in a "batch" process.
      Nearly 90% of the alpha-glucosidase activity was associated with midgut cells of
      sugar fed sandflies compared to only 46% in blood fed insects. Isoelectrofocusing
      revealed the presence of seven alpha-glucosidases with isoelectric points between
      4.3-5.8. No alpha-glucosidase activity was detected in the crop, indicating that
      glucosidases originate from the midgut epithelium rather than the salivary
      glands.

PMID- 9162545
TI  - [Clinical and physiopathological evaluation of general adaptation syndrome in
      patients with complicated closed thoracic trauma].

PMID- 9162546
TI  - [Features of respiration disorders in pre- and postoperative periods in patients
      with the tongue and face form of myasthenia].

PMID- 9162547
TI  - [Surgical treatment of stenosing lesions of the carotid arteries].

PMID- 9162548
TI  - [State of morbidity in goiter and thyroid cancer, their diagnosis and treatment].

PMID- 9162549
TI  - [Mechanisms of immunological changes in infectious endocarditis].

PMID- 9162550
TI  - [Lipid peroxidation in tissues of suppurative wounds in patients with diabetes
      mellitus].

PMID- 9162551
TI  - [Indicators of homeostasis as prognostic criteria of the development of
      postoperative complications in lung cancer in elderly patients].

PMID- 9162552
TI  - [Multifactorial analysis of risk of hemorrhage from esophageal varicose dilated
      veins in patients with decompensated liver cirrhosis].

PMID- 9162553
TI  - [Characteristics of the surgical treatment of gastroduodenal ulcer hemorrhage in
      patients with posthemorrhagic syndrome].

PMID- 9162554
TI  - [Indicators of nonspecific immunity in patients with gastrointestinal hemorrhage
      caused by peptic ulcer and correction of the disorder].

PMID- 9162555
TI  - [Role of endoscopic laser surgery in the surgical treatment of bronchial tumors].

PMID- 9162556
TI  - [Clinical analysis of surgical treatment in complications of recurrent gastric
      and duodenal ulcer].

PMID- 9162557
TI  - [Increase of safety of surgical interventions in aged patients by application of
      geriatric measures].

PMID- 9162558
TI  - [Prognostication of the development of early intestinal obstruction in children
      with abdominal pathology].

PMID- 9162559
TI  - [Use of ultra high frequency irradiation in hermetic closing of the surgical
      wound of the lung].

PMID- 9162560
TI  - [Supplying specialized surgical aid to patients with malignant neoformations of
      the organs of the hepato-pancreatico-biliary region].

PMID- 9162561
TI  - [Organization of a specialized center of surgery of liver, bile duct and
      pancreatic diseases in the regional public health system].

PMID- 9162562
TI  - [Analysis of morbidity, mortality and treatment methods of patients with cancer
      of the oropharynx in the Vinnitsa district].

PMID- 9162563
TI  - [Choice of the method of restoration of intestinal continuity after removal of
      the ileocecal region].

PMID- 9162564
TI  - [Changes in the body of patients with peptic ulcer after acute hemorrhage].

PMID- 9162565
TI  - [Functional rehabilitation of patients during 25-40 years after pulmonectomy].

PMID- 9162566
TI  - [A case report of a rare tumor of the thymic gland].

PMID- 9162567
TI  - [Case report of rarely occurring tumor of the thymic gland].

PMID- 9162568
TI  - [Case report of strangulated post-traumatic diaphragmatic hernia].

PMID- 9162569
TI  - [Use of liposomes and biologically active soluble antibiotics in the prevention
      and treatment of postoperative infectious-suppurative complications].

PMID- 9162570
TI  - [Report No. 1001 of the meeting of the Scientific Society of Surgeons of the City
      of Kiev and the Kiev region, 12/17/95].

PMID- 9162571
TI  - [Use of thoracoscopy in the treatment of post-traumatic coagulated hemothorax].

PMID- 9162572
TI  - Asthma among the famous. Benjamin Disraeli (1804-1881), British statesman and
      author.

PMID- 9162573
TI  - Asthma among the famous. Adb el-Kader (1808-1883), founder of the Algerian state.

PMID- 9162574
TI  - Asthma among the famous. Oliver Wendell Holmes (1809-1894), American physician,
      author, and philosopher.

PMID- 9162575
TI  - Maturity-onset diabetes of the young (MODY), MODY genes and non-insulin-dependent
      diabetes mellitus.
AB  - Maturity-onset diabetes of the young (MODY) is a genetically and clinically
      heterogeneous subtype of non-insulin-dependent diabetes mellitus (NIDDM)
      characterised by early onset, autosomal dominant inheritance and a primary defect
      in insulin secretion. To date, three MODY genes have been identified on
      chromosomes 20q [hepatocyte nuclear factor (HNF-4 alpha)/MODY1], 7p
      (glucokinase/MODY2) and 12q (HNF-1 alpha/MODY3). Mutations in glucokinase/MODY2
      result in mild chronic hyperglycaemia due to reduced pancreatic beta-cell
      responsiveness to glucose as well as decreased net accumulation of hepatic
      glycogen and increased hepatic gluconeogenesis following meals. In contrast,
      MODY1 and MODY3 are characterised by severe insulin secretory defects and major
      hyperglycaemia associated with microvascular complications. The role of the three
      known MODY genes in susceptibility to the more common late-onset from of NIDDM
      remains uncertain. Genetic studies seem to exclude any function as major
      susceptibility genes, although they may play a minor role in a polygenic context
      or a major role in particular populations.

PMID- 9162576
TI  - Quiz case of the month. Right ureteral-peritoneal fistula with haematoperitoneum.

PMID- 9162577
TI  - Spatially dynamic intercellular adhesion junction is coupled to a microtubule
      based motility system: evidence from an in vitro binding assay.
AB  - During spermatogenesis, spermatids change position in the seminiferous epithelium
      along an axis that is perpendicular to the seminiferous tubule wall. During this
      period, spermatids are attached to apical invaginations of Sertoli cells. In
      areas of this attachment, unique junction plaques occur in Sertoli cells. These
      plaques consist of regions of the plasma membrane involved with intercellular
      adhesion, a layer of actin filaments that are hexagonally packed, and an
      underlying cistern of endoplasmic reticulum (ER). It previously has been proposed
      that these junction plaques, and therefore the attached spermatids, are
      translocated, by motor proteins, along microtubule tracts in the Sertoli cell. If
      this is true, microtubules should bind to the junction plaque in a nucleotide
      dependent fashion. To verify this prediction, seminiferous epithelia of the rat
      were separated from tubule walls and then mechanically fragmented. These
      epithelial preparations were incubated, in both the presence and absence of 10 mM
      Mg(+)(+)ATP, with exogenous microtubules stabilized with taxol. Then unbound
      microtubules were separated from microtubules bound to larger epithelial
      components by centrifuging the samples through a step sucrose gradient. The
      fraction enriched for elongate spermatids was collected and processed for
      electron microscopy. The results indicate that the junction plaques remain
      attached to spermatids, the plaques are intact, and the cytoplasmic face of the
      ER binds microtubules in a nucleotide dependent fashion. The results are
      consistent with the presence of motor proteins on the ER component of the
      junction plaques and with the general hypothesis of microtubule-dependent
      spermatid translocation.

PMID- 9162578
TI  - [Indicators of maternal and infant health: implications of the 10th revision of
      the International Classification of Diseases].
AB  - Since the end of the 1940s, when the World Health Organization assumed
      responsibility for the decennial revisions of the Classification of Causes of
      Death, the Classification came to include diseases and definitions of use in
      vital statistics, resulting in the Sixth International Classification of Diseases
      (ICD-6). The most recent revision of this work, the International Statistical
      Classification of Diseases and Related Health Problems (ICD-10), is more
      significantly different than any revision since ICD-6, especially in the area of
      maternal and child health. Among the changes introduced in ICD-10 are the
      inclusion of obstetrical tetanus in the chapter on infectious diseases, which
      will facilitate the recording of this cause of maternal death; the incorporation
      of new definitions, such as late maternal death; and the redefinition of the
      perinatal period, which ICD-10 defines as starting at 22 completed weeks of
      gestation and ending 7 completed days after birth. This article seeks to
      highlight these changes and to discuss their consequences for the presentation
      and interpretation of indicators used in the evaluation of maternal and child
      health.

PMID- 9162579
TI  - [Production of scientific articles about health in six Latin American countries,
      1973-1992].
AB  - The production of articles resulting from biomedical, clinical, and public health
      studies that originated in Argentina, Brazil, Chile, Cuba, Mexico, and Venezuela
      from 1973 through 1992 was analyzed to discover trends in health research in
      Latin America. From the database of the Institute for Scientific Information
      (ISI), 41,238 articles with first authors who resided in those countries were
      extracted. These articles were analyzed by subject area, type of study, country,
      number of authors and institutions that participated in the investigation, and
      citations received by each article. Also analyzed were 95 articles in
      epidemiology selected from a pool of 570 published by authors from the six
      countries in 11 public health journals that enjoy international prestige. The
      results showed that the number of published works increased by 117% between the
      first and last five-year periods within the study period. Clinical research was
      distributed the most evenly among the countries, and public health research was
      the most concentrated (60.7% originated in Brazil). The numbers of biomedical and
      public health research articles showed relatively more growth than those
      reporting on clinical research throughout the period. A relative decrease was
      found in articles by only one author, which suggests a greater frequency of team
      efforts, and an increase was seen in articles with authors tied to two or more
      national or foreign institutions, which indicates greater cooperation between
      institutions and countries. The average number of citations received by each
      article was 3, which was less than half the number received by the articles in
      the ISI database (7.78). Regarding the subset of 95 articles in epidemiology, the
      great majority (96%) dealt with infectious diseases or maternal and child health,
      while in the international literature 78% of such articles were about chronic
      diseases. This group of articles gave evidence of more cooperation with
      international institutions and had a citation index of 4.36 per article. It is
      concluded that, despite the inherent limitations, this type of study reveals some
      general trends in the development of research in the six Latin American countries
      with the greatest scientific production and makes it possible to formulate
      hypotheses on the factors that influence these trends. Taken with the paper
      caution, the results of studies like this one can be of great value in defining
      health science and technology policies.

PMID- 9162580
TI  - [Ecology of Vibrio cholerae serogroup 01 in aquatic environments].
AB  - The endemic and seasonal nature of cholera depends upon the survival of Vibrio
      cholerae 01 in a viable but not necessarily culturable state in ecologic niches
      in aquatic environments during interepidemic periods. To understand the ecology
      of V. cholerae it is necessary to know which aquatic ecosystems can harbor it and
      thus contribute to the endemic presence of cholera in Latin America. This article
      presents a summary of the ecology of V. cholerae 01, organized according to the
      abiotic and biotic factors that are relevant to the microbe's survival in aquatic
      environments. This pathogen finds favorable conditions in waters characterized by
      moderate salinity, high nutrient content, warm temperature, neutral or slightly
      alkaline pH, and the presence of aquatic macrophages, phytoplankton, zooplankton,
      fish, mollusks, and crustaceans. These ecologic conditions are typical of
      estuaries and coastal swamps, and toxigenic V. cholerae 01 is now considered an
      autochthonous member of the microbial flora of these environments. The
      microorganism has also shown the ability to colonize freshwater ecosystems in its
      viable but not necessarily culturable form, if organic or inorganic substrates
      that favor its survival are available.

PMID- 9162582
TI  - [Usefulness of studies on antitubercular drug resistance].

PMID- 9162583
TI  - [WHO report on intradermal application of rabies vaccines].

PMID- 9162585
TI  - [Susceptibility of Biomphalaria tenagophila from the Parana and Uruguay River
      basins to Schistosoma mansoni].
AB  - To study the possibility that schistosomiasis might be able to spread into the
      basins of the Parana and Uruguay rivers, 1,711 snails were experimentally exposed
      to infection with Schistosoma mansoni. These snails were laboratory-bred progeny
      of Biomphalaria tenagophila collected from 15 populations in the geographic area
      under consideration. Three strains of S. mansoni were used: BH2, adapted to B.
      glabrata, and SJ and SJ2 adapted to B. tenagophila. None of the 543 snails
      exposed to the BH2 strain became infected, nor did any of the 668 exposed to SJ.
      However, of the 500 exposed the SJ2, 4 of the 163 snails (2%) from Ayolas, a
      locality in the Parana basin, were susceptible, as were 8 of 45 (18%) from
      Fuente, Salto, in the Uruguay basin. These findings are similar to those of
      studies done in other geographic areas, where some populations of B. tenagophila
      do not become infected with S. mansoni while others are susceptible. The results
      of this study signal the possibility of the expansion of schistosomiasis into a
      broad region of South America in which B. tenagophila is found.

PMID- 9162584
TI  - [Epidemic of Venezuelan equine encephalitis].

PMID- 9162586
TI  - [The Canadian health system and its financing].
AB  - This work stems from a brief visit in 1993 to the Canadian health services as
      part of the PAHO International Health Training Program and the subsequent
      research, discussion, and analysis relating to that experience. By no means is
      this paper an exhaustive account of the system, but rather a close look at one of
      its aspects: financing. The main objective is to identify some of the virtues and
      limitations of a health system that is considered one of the most efficient,
      effective, and equitable in the world. Although the Canadian health system is
      financed by the federal government and the provincial governments, cost
      containment is a constant concern, since factors such as the growing use of
      highly complex technologies, hospital care, and long-term treatment of chronic
      and degenerative illnesses tend to increase costs. The progressive reduction in
      the federal budget has lead to more efficient use of resources and the
      rationalization of installed capacity. At the same time, the relative simplicity
      of the system's operation has permitted administrative costs to be kept low. In
      addition, alternative forms of care, such as local centers for community-based
      care, care at home and in special institutions to promote the maximum level of
      self-sufficiency, and the use of volunteers, have been devised in order to
      partially control cost increases. The people's participation in planning and
      decision-making permit them to guide the development of the health services.
      Nevertheless, given the current situations, it is essential that the system be
      modified to prepare it for the challenges the twenty-first century will bring.

PMID- 9162587
TI  - [Surveillance and active search of suspected cases of hemorrhagic dengue in
      Ribeirao Preto, Sao Paulo].
AB  - A clinical-epidemiological case study was carried out to evaluate a surveillance
      and active search system for suspect cases of dengue hemorrhagic fever/dengue
      shock syndrome (DHF/DSS) during a dengue epidemic in the Ribeirao Preto
      municipality, State of Sao Paulo, Brazil, between November 1990 and March 199.
      This was the first dengue epidemic ever recorded in this region. Although dengue
      is a growing public health problem in Brazil, and DHF/DSS has been reported to be
      evolving in the Americas, health officials have shown a passive attitude towards
      the disease, partly due to lack of experience. Reporting dengue occurrences, both
      of isolated cases and of epidemics, is essential to reduce mortality. The data
      analyzed were collected through the official epidemiological surveillance system
      during the 1990-1991 epidemic. Out of 2,521 confirmed cases of dengue, 34 cases
      of febrile acute illness with hemorrhagic manifestations were identified as
      possible cases of DHF/DSS, as well as two deaths associated to dengue. From these
      36 cases, 12 cases were confirmed by laboratory exams as dengue with hemorrhagic
      manifestations. Examinations of clinical and laboratory data, and results of the
      autopsies suggested that the two deaths were cases of primary DHF/DSS. The
      difficulty of the health system in establishing the clinical suspicion of DHF/DSS
      was confirmed in the study. This resulted in delayed and inadequate clinical
      procedure. The present study also confirmed the need for a permanent active
      epidemiological surveillance system for the early identification of DHF/DSS
      suspect cases thus enabling quick and adequate control actions.

PMID- 9162588
TI  - [Factors associated with the initiation of breast feeding by women in the
      Dominican Republic].
AB  - The determinants of initiating breast-feeding vary among different populations,
      but knowledge of them is of fundamental importance for guiding programs to
      promote breast-feeding. Data from the Demographic and Health Survey of 1991 in
      the Dominican Republic were used to identify factors associated with the
      initiation of breast-feeding in a random sample of women of reproductive age.
      Approximately 93% of 2,714 mothers reported having begun to breast-feed their
      last live-born child who was currently under 5 years of age, and that percentage
      had not changed substantially in the past 5 years. A logistic regression analysis
      was done in which odd ratios (psi) were calculated as measures of association.
      Women who had suffered some type of illness during pregnancy (psi = 2.3), those
      whose child had a low birthweight (psi = 2.9), primiparas (psi = 1.9), and those
      with medium (psi = 1.6) or high (psi = 2.1) income levels showed a significantly
      higher risk of not starting to breast-feed. These women should be considered
      priority groups by breast-feeding promotion programs.

PMID- 9162589
TI  - [Detection of Neisseria meningitidis group B antigens by MB-Dot-Elisa test in
      patients with meningitis].
AB  - Infection with Neisseria meningitidis group B has been difficult to detect,
      partly because this bacterial group's polysaccharide is a weak immunogen. This
      article describes work carried out to test a new procedure (MB-Dot-ELISA)
      employing a high-titered horse antiserum for detection of N. meningitidis group B
      antigens. The study assayed cerebrospinal fluid samples from 585 subjects, 574
      with suspected meningitis cases and 11 with neurologic disorders. The results of
      the assay indicated a sensitivity of 0.991 and a specificity of 0.826. These
      results were superior to those obtained with latex agglutination and in
      substantial agreement with the results of counterimmunoelectrophoresis and
      bacteriologic methods. Overall, the MB-Dot-ELISA was found to be sensitive,
      inexpensive, and suitable for public health laboratory investigations.

PMID- 9162592
TI  - [Abnormally broad confidence intervals in logistic regression: interpretation of
      results of statistical programs].
AB  - This study describes the behavior of eight statistical programs (BMDP, EGRET,
      JMP, SAS, SPSS, STATA, STATISTIX, and SYSTAT) when performing a logistic
      regression with a simulated data set that contains a numerical problem created by
      the presence of a cell value equal to zero. The programs respond in different
      ways to this problem. Most of them give a warning, although many simultaneously
      present incorrect results, among which are confidence intervals that tend toward
      infinity. Such results can mislead the user. Various guidelines are offered for
      detecting these problems in actual analyses, and users are reminded of the
      importance of critical interpretation of the results of statistical programs.

PMID- 9162593
TI  - [Work and high-risk pregnancy due to diabetes: two incompatible circumstances].
AB  - In 1991 the prevalence of diabetes was 7.6% in women in nine Brazilian state
      capitals. This disease now ranks among the leading causes of death in the country
      and is becoming an increasingly alarming public health problem. In spite of
      advances in the treatment of diabetes and improved obstetric care, gestational
      diabetes puts a pregnant woman at high risk of spontaneous abortion,
      ketoacidosis, hypoglycemia, hypertension, and other serious disorders. This study
      used life histories to investigate the relationship between health, sexuality,
      and work in five working women who were diabetic and pregnant and who received
      care at the Prenatal Care Outpatient Clinic of the San Pablo Hospital. All these
      women had non-insulin-dependent diabetes mellitus, were between 26 and 43 years
      old, and earned from US$ 150 to 375 per month for working 8-hours days, with one
      day off each week. Two of the women's male partners were unemployed; all of the
      women performed household chores during their day off. Quotations taken directly
      from conversations with the five participants reveal: the difficulty of caring
      for children and working; the sexual harassment that some of them suffered; the
      conflict and dissatisfaction associated with work; the myth of the natural joy of
      motherhood; the sexual control exercised by males; the interference of working
      conditions and work activities with pregnancy; and the perception that they did
      not have legal protection owing to employers' lack of respect for workers' rights
      and for the maternity protection provisions of the Federal Constitutional of
      Brazil. It is concluded that health policies should pay greater attention to
      improving the quality of life of working women, especially if they suffer from
      diabetes and are pregnant.

PMID- 9162594
TI  - [The fragmentation of national health systems].
AB  - The nationalistic tendencies observed in the world today, rooted in ethnic and
      ancestral cultural values that do not necessarily coincide with the physical
      boundaries of countries, have an enormous influence on societal organization, the
      distribution of wealth, and the processes of decentralization being carried out
      by governments. At the same time, the economic liberalization policies which are
      in fashion accentuate social divisions and favor models of health care that are
      fragmented according to the economic means of the user. This document explores
      the consequences of these trends for equity in the health and medical insurance
      systems of Latin America, as well as the role of the State and the private sector
      in the provision of services.

PMID- 9162595
TI  - [The United Nations confronts the challenges of a changing world: the 49th Annual
      DPI/NGO Conference].
AB  - The United Nations (UN), previously considered a forum exclusively for sovereign
      governments, has changed over time in tune with various political, economic,
      social, and cultural phenomena. One of these is the growing presence of
      nongovernmental organizations (NGOs) in international agencies and activities.
      The 49th Annual Conference of the Department of Public Information and NGOs, held
      at UN headquarters on 10 September 1996, analyzed the extent to which the UN is
      allowing NGOs to participate in its discussions of policy, institutional reform,
      and field operations. The issues discussed at the Conference and the challenges
      that face the UN in a changing world from the subject of this report.

PMID- 9162596
TI  - Brain imaging and psychogeriatric services in geriatric psychiatry. Proceedings
      of the 23rd Symposium of the European Association of Geriatric Psychiatry. Lund,
      Sweden, October 6-7, 1995.

PMID- 9162598
TI  - [Chronic inflammatory bowel diseases. Introduction].

PMID- 9162597
TI  - Studies on the "signal" constituents for the evaluation of animal crude drugs.
      III. Nucleic acid components.
AB  - An analytical method for determining the contents of 7 nucleic acid bases, 6
      ribonucleosides and 5 deoxyribonucleosides in animal crude drugs were
      established. The contents in free nucleic acid components (the ice-cold extracts)
      and in total nucleic acid components (the heated extracts) of 8 crude drugs were
      quite different from one another, indicating that these content patterns could be
      used as a "signal" of each animal crude drug. For example, the contents of
      inosine in Lumbricus, uracil in Cervi Parvum Cornu, and guanine and hypoxanthine
      in Hippocampus were high. The total contents in each crude drug were about twice
      or three times as large as the free contents. The main degradation products by
      the heated extracts were adenine and guanine. These results suggested that the
      contents of nucleic acid components could be one of the "signal" constituents for
      evaluation of animal crude drugs.

PMID- 9162599
TI  - [Epidemiology and pathogenesis of Crohn's disease].
AB  - The onset of Crohn's disease (CD) is more frequent between 15 and 30 years and
      also has a second peak over 60 years. It female sex it is slightly more prevalent
      among female. Incidence rates vary in different geographic areas, ranging from 2
      to 4 new cases/100,000 inhabitants/year. Prevalence data range from 1.2 to
      200,000/100,000. Ethnic differences are beginning to disappear, underlining the
      role of environmental factors in the genesis of the disease. At the moment the
      most reliable hypothesis is that CD has a multifactorial pathogenesis: antigenic
      and environmental factors acting in genetically predisposed patients. According
      to this hypothesis, first degree relatives of CD patients have a relative risk of
      disease ranging from 2 to 4. Many infective agents have been associated with its
      onset and relapse; the most reliable observations are those related to the
      measles virus. There is an activation of the immunosystem which is shown by
      abnormal T-cell activation, by the increase of some cytokines and by the
      expression of adhesion molecules. The role of oral contraceptives and diet as
      risk factors is controversial. Smoking is the only risk factor positively
      associated with the onset of CD and its clinical course; this association is
      specific and dose-related.

PMID- 9162600
TI  - [Repair of stricture in Crohn's disease: treatment of choice?].
AB  - Strictureplasty has become one of the surgical options available for skip-lesions
      and for duodenal, multiple small bowel or anastomotic strictures caused by
      Crohn's disease. Over a sixteen-year period, 44 patients underwent
      strictureplasty for 269 symptomatic strictures associated with Crohn's disease.
      After a median follow-up of 50 months (range 18-89) a second additional operation
      for symptomatic recurrence was performed in 10 patients, two of whom developed
      new symptomatic strictures after 3 and 36 months, requiring a third operation. Of
      all the strictures present at surgery, 174 were treated performing
      strictureplasties (156 were closed transversely using Heineke-Mickulicz, 16 in a
      side-to-side Finney fashion and 2 in the manner of Jabolay) and 88 with
      synchronous resection. Furthermore, 7 other strictures were treated with a side
      to-side ileocolic (5 strictures in 3 patients) or ileoileal (2 strictures in one
      patient) anastomosis. No operative mortality was recorded and there were no
      septic complications due to anastomotic leak. The mean follow-up period was 47.8
      +/- 42.4 months (range 3-132). Symptomatic restrictures of previous
      strictureplasty sites requiring surgery occurred in 8.8% of cases. Furthermore,
      no statistically significant difference (Kaplan-Meier) was observed in the
      reoperation rate among patients affected respectively by skip lesions or multiple
      strictures or among patients treated only by strictureplasty or with an
      associated resection. We concluded that strictureplasty is a valuable adjunct to
      resection in the treatment of Crohn's strictures.

PMID- 9162601
TI  - [Postoperative recurrence in Crohn's disease].
AB  - Intestinal resection in the natural history of Crohn's disease is a forced step.
      Unfortunately surgery is not curative as disease inexorably recurs. The frequency
      of recurrence varies according to the definitions adopted, being high when
      endoscopical criteria are used (70-90% at one year). Among risk factors, the most
      convincing is a smoking habit. The pathogenesis of recurrence is still unknown.
      Particular attention was paid to colo-ileal reflux which occurs after the
      resection of the ileocecal valve. The diagnosis should always be based on
      morphological criteria (endoscopy or radiology). In fact symptoms occur late and
      are often uncharacteristic. A particular problem in the management of patients
      with Crohn's disease is the prevention of post-operative recurrence. Recent
      randomized, controlled trials of which the first has been published by the
      authors of this article, demonstrated that the administration of 5-ASA early
      after resection may prevent, delay or attenuate such recurrences. Cessation of
      smoking also plays a central role in prevention. The final message is that in
      active Crohn's disease surgery should not be excessively delayed. Early resection
      followed by prophylactic treatment seems to improve the quality of life in
      patients with more severe Crohn's disease.

PMID- 9162603
TI  - Whither Primary Care?

PMID- 9162602
TI  - [Prevention of infectious postoperative complications in Crohn's disease].
AB  - Mortality and post-operative complications are elevated in Crohn's disease, for
      many reasons: pre-existing septic complications, malnutrition, impaired cell
      mediated immunity, failure to identify enteric fistulas and/or abdominal abscess
      during surgical operation. From 1984 to 1996 in 383 patients with Crohn's disease
      we performed 426 surgical procedures, observing post-operative complications in
      28 of these (6.5%). However, septic complications in the surgical field were only
      7 (1.6%). A 83-year-old patient died after surgery because of heart failure. The
      risk of post-operative complications was significantly higher in patients with
      elevate Prognostic Nutritional Index (PNI). We treated patients with malnutrition
      pre-operatively using parenteral nutrition (TPN). In 100 patients undergoing TPN
      we observed a significant PNI reduction (from 53.3 +/- 13 to 42.1 +/- 6.9) and a
      significative improvement of transport proteins correlated with nutritional
      status, such as pre-albumin (from 21.2 mg/dl +/- 9.8 to 26.5 mg/dl +/- 7.8) and
      retinol binding protein (from 3.8 mg/dl +/- 1.6 to 4.6 mg/dl +/- 1.7). During
      surgical operations we recorded fistulas caused by disease, observing 336
      fistulas in 258 patients. The treatment of fistulas (by suture or less frequently
      by resection of the intestinal tract involved in the inflammatory process)
      prevented septic post-operative complications: indeed we did not observe enteric
      fistulas in any patient post-operatively. We conclude that the improvement of
      nutritional status and the adequate treatment of enteric fistulas prevents septic
      complications in nearly all patients.

PMID- 9162604
TI  - Treatment of dyslipoproteinaemia in diabetes mellitus.
AB  - Coronary heart disease (CHD) is the most common cause of premature death in
      diabetes. Hypercholesterolaemia occurs in diabetes with about the same frequency
      as in the general population, but it confers a greater risk of CHD in diabetes.
      Hypertriglyceridaemia and low serum high density lipoprotein (HDL) cholesterol
      levels are more common in diabetes, particularly non-insulin-dependent diabetes.
      Nephropathy increases the severity of dyslipoproteinaemia. There remains a
      reluctance to apply the results of cholesterol-lowering trials to diabetes. No
      trial has been specifically in diabetes, but this should not constrain the
      treatment of diabetic patients at clearly high CHD risk. It is suggested that
      fasting lipids should be measured in all diabetic patients aged less than 70
      years with established CHD or whose non-fasting cholesterol is >6.00 mmol I(-1)
      or triglycerides >3.00 mmol I(-1). For those with raised lipids glycaemic control
      should be improved, if possible, and dietary therapy aimed at a decrease in fat
      intake, particularly saturated fat, and weight reduction in the obese. Lipid
      lowering drugs are required in patients with CHD and serum cholesterol >5.5 mmol
      I(-1) with the aim of decreasing non-HDL to <4.00 mmol I(-1). In patients without
      CHD lipid-lowering drugs should be considered when serum cholesterol exceeds 6.5
      mmol I(-1) and the risk of CHD is greater than 20 % over the next 10 years. There
      is no evidence that pursuing this policy beyond the age of 70 years is
      beneficial. Diabetic women with dyslipoproteinaemia should, however, be treated
      in the same way as men. The knowledge that hypertriglyceridaemia and low serum
      HDL cholesterol are present helps in the assessment of CHD risk and the choice of
      medication to decrease non-HDL cholesterol, but there is no evidence that their
      treatment in the absence of raised cholesterol is of benefit.

PMID- 9162605
TI  - Central role of TGF-beta in the pathogenesis of diabetic nephropathy and
      macrovascular complications: a hypothesis.
AB  - Patients with insulin-dependent diabetes mellitus (IDDM) and albuminuria are at
      high risk for severe micro- and macrovascular complications. Diabetic vascular
      complications are characterized by structural alterations of extracellular matrix
      (ECM) components in glomeruli and large vessel walls, namely, accumulation of
      collagen IV, collagen VI and fibronectin and relative decrease of heparan
      sulphate proteoglycan (HSPG). We hypothesize that the defect remodelling of ECM
      contributing to nephropathy and macrovascular disease is induced by
      overproduction of transforming growth factor-beta (TGF-beta). Recent reports
      indicate that hyperglycaemia, increased intraglomerular pressure, and glycated
      proteins potentially induce overproduction of TGF-beta in diabetes. TGF-beta
      stimulates production of ECM components such as collagen IV, fibronectin,
      proteoglycans (decorin and biglycan) without increasing HSPG. TGF-beta
      overproduction leads to glomerulosclerosis and TGF-beta is a causal factor in
      myointimal hyperplasia after balloon injury of carotid artery. It mediates
      angiotensin II modulator effect on smooth muscle cell growth. These findings may
      indicate TGF-beta overproduction to be a common pathogenetic step explaining the
      well-known association between micro- and macrovascular complications in diabetic
      patients. TGF-beta antagonists, such as decorin, betaglycan, and possibly also
      heparin, might be potential candidates for future therapy to prevent diabetic
      vascular disease.

PMID- 9162606
TI  - Diastolic dysfunction in patients with non-insulin-dependent diabetes mellitus of
      short duration.
AB  - To determine whether abnormal left ventricular diastolic function is present at
      an early stage of non-insulin-dependent diabetes mellitus (NIDDM), left
      ventricular diastolic filling was evaluated by pulsed doppler echocardiography in
      16 normotensive patients with NIDDM of short duration (1.8 +/- 1 years, mean +/-
      SD) and no evidence of microangiopathy, and in 16 healthy volunteers comparable
      for age, body mass index, and sex distribution. All patients showed normal
      systolic function. The interventricular septum thickness, left atrial diameter,
      and left ventricular mass index were increased in the diabetic as compared with
      the control group (p < 0.01, p < 0.01, and p < 0.02, respectively). Isovolumic
      relaxation time and atrial peak filling velocity were greater in diabetic
      patients (p < 0.001, and p < 0.01, respectively), whereas early to atrial peak
      filling velocity ratio was significantly reduced (p < 0.05). This study
      demonstrates that an impairment of left ventricular diastolic function occurs
      early in the natural history of NIDDM, and that this abnormality is unlikely to
      be related to clinical evidence of microangiopathic complications.

PMID- 9162607
TI  - Fetal growth and insulin resistance in adult life: relationship between glycogen
      synthase activity in adult skeletal muscle and birthweight.
AB  - Growth retardation during fetal life is associated with insulin insensitivity and
      an increased prevalence of impaired glucose tolerance in adult life. Because
      insulin-mediated stimulation of glycogen synthase may be an important rate
      limiting step for insulin action at the cellular level, we have sought to
      determine whether impaired activation of muscle glycogen synthase is linked with
      early growth retardation. Postprandial glycogen synthase activity was therefore
      measured in muscle biopsies from a group of 27 women with normal glucose
      tolerance aged around 50 who were born in Preston, Lancashire, whose birthweight
      and body size at birth were recorded. Glycogen synthase activity measured at 0.1
      mmol 1(-1) glucose-6-phosphate correlated with insulin sensitivity as measured by
      a short insulin tolerance test (r = 0.42, p < 0.05) and the waist to hip ratio (r
      = -0.48, p < 0.01), but not body mass index, body fat percentage or age. Within
      the group of women with normal glucose tolerance there was no relationship
      between intra-uterine growth as evidenced by birthweight or body size at birth
      and the response to insulin of skeletal muscle glycogen synthase in adult life.
      Thus we found no evidence for a direct link between fetal growth and insulin
      sensitivity in this pathway.

PMID- 9162609
TI  - The onset of NIDDM and its relationship to clinical diagnosis in Egyptian adults.
AB  - The onset of diabetes relative to clinical diagnosis was estimated in Egyptians
      with non-insulin-dependent diabetes mellitus (NIDDM) based on the relationship
      between retinopathy and duration of diabetes. Between July 1992 and October 1993
      the Diabetes in Egypt (DIE) Project performed a cross-sectional, population-based
      survey with clinical and laboratory follow-up to describe the prevalence of
      microvascular, neuropathic, and macrovascular complications among Egyptians > or
      = 20 years of age with diagnosed diabetes, previously undiagnosed diabetes,
      impaired glucose tolerance, and normal glucose tolerance. The sample of persons
      with diabetes diagnosed prior to the survey had medical examinations which
      included a dilated eye examination and retinal photographs. Generalized linear
      models were used to relate the probability of retinopathy to duration of
      diabetes. Among 218 persons with diabetes diagnosed prior to the DIE project, 87
      (40%) had diabetic retinopathy. The onset of retinopathy was estimated to occur
      2.6 years (p = 0.04) prior to clinical diagnosis. The estimated annual incidence
      of retinopathy was 5% and the estimated prevalence at the time of clinical
      diagnosis of diabetes was 12%. On the basis of reports that retinopathy does not
      occur until approximately 5 years after the development of diabetes, the onset of
      NIDDM was estimated to occur 7.6 years prior to its clinical diagnosis. This
      estimate of the onset of NIDDM in Egyptians is comparable to other estimates
      reported for US and Australian populations.

PMID- 9162608
TI  - A higher proinsulin response to glucose loading predicts deteriorating fasting
      plasma glucose and worsening to diabetes in subjects with impaired glucose
      tolerance.
AB  - To evaluate the clinical significance of proinsulin determination, we measured
      glucose, insulin, C-peptide and proinsulin during 75-g oral glucose loading in 59
      patients. In a 2.5-year follow-up study of 37 subjects with impaired glucose
      tolerance (IGT) at the initial test, 11 patients changed from IGT to a normal
      state and 5 patients showed worsening to overt Type 2 diabetes with elevation of
      fasting plasma glucose; 21 patients remained unchanged. Although our data showed
      that both fasting (IGT: p = 0.4523) and 120-min plasma glucose (IGT: p = 0.8168)
      values at the initial test were not significantly correlated with increased
      fasting plasma glucose levels in a 2.5-year follow-up study, subjects with a
      higher 120-min proinsulin response to glucose during the initial OGTT showed a
      significant correlation (IGT: p < 0.0001) with increased fasting plasma glucose
      levels after follow-up period and developed Type 2 diabetes. The present findings
      suggest that the proinsulin response to glucose loading might be a useful
      indicator for predicting worsening to diabetes in subjects with impaired glucose
      tolerance.

PMID- 9162610
TI  - Relationship between insulin sensitivity and insulin receptor substrate-1
      mutations in non-diabetic relatives of NIDDM families.
AB  - Insulin receptor substrate-1 (IRS-1) occupies a key position in the insulin
      signalling pathway. Two mutations of the IRS-1 gene (Gly(972)Arg and Ala(513)Pro)
      have been described, although their roles in the development of insulin
      resistance and non-insulin-dependent diabetes mellitus (NIDDM) remain
      controversial. Insulin resistance has been described in non-diabetic relatives of
      NIDDM families, suggesting that it may be due to an inherited defect of insulin
      action. We therefore examined the relationships between the two mutations and
      insulin sensitivity in 93 non-diabetic first degree relatives from North European
      families with 2 or more living NIDDM subjects. Anthropometric measurements, an
      oral glucose tolerance test, and an insulin tolerance test to assess insulin
      sensitivity (K(ITT)) were performed. Basal insulin sensitivity was assessed by
      homeostasis model assessment (HOMA). Comparisons were made between the following
      relative subgroups: with (n = 9) and without (n = 84) the 972 mutation; with (n =
      5) and without (n = 88) the 513 mutation; and with either one or both mutations
      (n = 13) or without either (n = 80). General linear model analysis was used to
      compare K(ITT) and HOMA between the subgroups with the anthropometric variables
      known to influence insulin sensitivity as covariates. There were no significant
      differences between the subgroups for K(ITT) and HOMA. In conclusion, the 513 and
      972 mutations, alone and in combination, are not associated with decreased
      insulin sensitivity in non-diabetic relatives of NIDDM families.

PMID- 9162611
TI  - A comparative study of responses to acute hypoglycaemia induced by human and
      porcine insulins in patients with Type 1 diabetes.
AB  - The effects of human and porcine insulins on the symptomatic, physiological, and
      counterregulatory hormonal responses to acute hypoglycaemia were compared in 40
      patients with Type 1 diabetes, 20 of whom were newly diagnosed while 20 had been
      treated for between 5 and 20 years. In a double-blind, cross-over trial all
      patients were treated with human or porcine insulin, in random order, for two
      consecutive 3-month periods. At the end of each treatment period they were
      subjected to an acute episode of experimental hypoglycaemia induced by a
      continuous intravenous infusion (2.0 mU kg(-1)min(-1)) of the same insulin
      species. Haemodynamic, sweating, and tremor responses were measured during both
      studies, symptom scores were recorded and the arterialized plasma glucose
      thresholds for autonomic activation and the onset of subjective symptoms were
      identified. In all patients the glycaemic thresholds for the initiation of the
      autonomic physiological responses to hypoglycaemia and the onset of the
      symptomatic response were concurrent and did not differ with insulin species
      (plasma glucose 1.94 vs 1.96 mmol I(-1), human vs porcine studies). The onset,
      temporal pattern, nature, and magnitude of the physiological responses (sweating,
      heart rate, blood pressure, and tremor) during acute experimental hypoglycaemia
      were also identical with each insulin species. The magnitude and temporal pattern
      of the response of counterregulatory hormones (adrenaline, noradrenaline,
      glucagon, ACTH, and GH) to hypoglycaemia as induced by human and porcine insulins
      were indistinguishable, as were the total and individual scores of autonomic and
      neuroglycopenic symptoms. In conclusion, in patients who had newly diagnosed and
      intermediate duration (5-20 years) of diabetes, the symptomatic, physiological,
      and counterregulatory hormonal responses to acute insulin-induced hypoglycaemia
      did not differ between human and porcine insulins, and the plasma glucose
      thresholds at which the symptomatic and autonomic responses were initiated were
      identical with both insulin species. This study does not support the hypothesis
      that treatment with human insulin modifies the symptomatic, physiological, and
      counterregulatory hormonal responses to acute hypoglycaemia.

PMID- 9162612
TI  - Effect of partially depolymerized guar gum on acute metabolic variables in
      patients with non-insulin-dependent diabetes.
AB  - Fourteen patients with non-insulin-dependent diabetes (NIDDM) attended the study
      centre on 4 mornings separated by at least 3 days, to receive in random order 75
      g carbohydrate breakfast meals of control or guar breads with jam and butter.
      Guar gum flours of low, medium, and high molecular weight (MW) were incorporated
      into wheat bread rolls to provide 7.6 g guar per meal. Venous blood samples were
      taken via an indwelling cannula in a forearm vein at fasting and at eight
      postprandial times and then analysed for blood glucose, plasma insulin, C
      peptide, and gastric inhibitory polypeptide (GIP). Guar gum bread significantly
      reduced the postprandial rise in blood glucose, plasma insulin, and, except for
      bread containing low MW guar gum, plasma GIP levels compared to the control.
      Thus, the partial depolymerization of guar gum does not diminish its
      physiological activity. No reductions in postprandial plasma C-peptide levels
      were seen after any of the guar bread meals. This suggests that guar gum
      attenuates the insulin concentration in peripheral venous blood in patients with
      NIDDM by increasing the hepatic extraction of insulin.

PMID- 9162613
TI  - Effect of combination therapy of troglitazone and sulphonylureas in patients with
      Type 2 diabetes who were poorly controlled by sulphonylurea therapy alone.
AB  - The clinical efficacy of troglitazone, a new oral hypoglycaemic agent was
      investigated in Type 2 diabetes in combination with sulphonylureas. Two hundred
      and ninety-one patients with Type 2 diabetes (age 21-81 years) whose previous
      glycaemic control by sulphonylureas was judged stable but unsatisfactory (fasting
      plasma glucose (FPG) > 8.3 mmol I-1) were randomly allocated into the
      troglitazone treatment group (troglitazone group, n = 145) or the placebo
      treatment group (placebo group, n = 146). They were treated by test drugs for 12
      weeks in combination with the same dose of sulphonylureas before the trial. One
      hundred and twenty-two patients who received troglitazone and 126 patients who
      received placebo were evaluated for efficacy. The baseline characteristics did
      not differ significantly between the two groups. In the troglitazone group, FPG
      and HbA(1c) decreased significantly after the treatment (before vs after, FPG:
      10.8 +/- 2.0 mmol I(-1) vs 9.2 +/- 2.5 mmol I(-1), p< 0.001; HbA(1c): 9.2 +/-
      1.4% vs 8.5 +/- 1.5%, p< 0.001). FPG and HbA(1c) did not change after the
      treatment in the placebo group (before vs after, FPG: 10.5 +/- 1.7 mmol I(-1) vs
      10.7 +/- 2.2 mmol I(-1); HbA(1c): 9.0 +/- 1.5% vs 9.2 +/- 1.6 %). Serum total
      cholesterol and HDL-cholesterol did not change in either group, however, serum
      triglyceride significantly decreased in the troglitazone group. No serious
      adverse events occurred in either group. In conclusion, troglitazone 400 mg day(
      1) had a significant hypoglycaemic effect in combination with sulphonylureas
      without any serious adverse events. Troglitazone, developed as an insulin action
      enhancer, can be a useful hypoglycaemic agent in the treatment of patients with
      Type 2 diabetes who are not well controlled by sulphonylureas alone.

PMID- 9162615
TI  - Influence of morbidity and health care structure on hospitalization among adult
      diabetic patients.
AB  - The aim of the study was to investigate the influence of outpatient care, overall
      hospital bed provision and the prevalence of diabetes on the hospital use by
      adult diabetic patients. Population based data were collected in Finland from a 3
      year period. Hospital admissions, inpatient days, and mean length of stay due to
      diabetes were derived from the Hospital Discharge Register. Estimates of diabetes
      prevalence were derived from the Central Drug Register. Primary outpatient site,
      annual number of physician visits, and age at onset among diabetic patients were
      assessed by questionnaire. The unit of analysis was hospital district (n = 21)
      and all analyses refer to the 15-64 years age group. Linear regression models
      were used to explain discharge rates and inpatient days in the district. Large
      variations between hospital districts were observed in diabetes prevalence,
      discharge rates due to diabetes, and mean length of stay among diabetic patients.
      Prevalence of diabetes and overall supply of hospital beds in the district were
      not related to hospital use. Univariate analyses showed that the larger the
      proportion of diabetic patients primarily using a private practitioner, the lower
      the hospital use. In districts where early onset of diabetes was more common, the
      average number of inpatient days was significantly lower than in other districts.
      In stepwise regression analyses, early onset of diabetes was the only variable
      that entered the models. In the full model, 24.6% of the variance in inpatient
      days and 16.1% of the variance in discharge rates were explained. In conclusion,
      factors related to health care structure, provision of hospital beds or morbidity
      explain little of the regional variation in hospital use. The observed variations
      in hospital use probably depend mainly on local treatment policies and
      differences in clinical decision-making.

PMID- 9162614
TI  - The epidemiology of diabetes and its complications in New Zealand.
AB  - New Zealand is a country in the South Pacific with a high proportion of
      Polynesians. While the prevalence of diabetes appears the same in New Zealand
      Europeans as Europeans elsewhere, Maori and Pacific Islands people have a 2 to 4
      fold excess prevalence of diabetes. Although Europeans make up the majority of
      diabetic New Zealanders, the greatest concern lies with the Maori and Pacific
      Islands patients who experience an earlier age at diagnosis, greater obesity,
      higher rates of smoking (in Maori), poorer diabetes knowledge, poorer glucose
      control, and more end stage renal failure and blindness. Efforts are now being
      made to control the current epidemic.

PMID- 9162616
TI  - Health related quality of life in diabetic patients measured by the Nottingham
      Health Profile.
AB  - The aim of the present study was to assess the health related quality of life of
      adult diabetic patients using the Nottingham Health Profile (NHP) as a measure. A
      further aim was to describe different Quality of Life (QOL) outcomes in different
      treatment groups of diabetes. The target population consisted of all registered
      adult (18 years or older) diabetic patients (n = 2519) in the district of Oulu, a
      city of 100 000 inhabitants in Northern Finland. All these persons were invited
      to participate in a screening examination for diabetic retinopathy, and the NHP
      questionnaire was mailed along with this invitation. A total of 1804 patients
      (72%) returned the NHP questionnaire when they came to the fundus photography
      session. The data were analysed by using mean values of NHP dimensions with the
      95% confidence intervals (CI) and the logistic regression analysis to predict the
      risk (OR) for having at least one health problem in a particular dimension. The
      results indicated that patients with tablet treatment had significantly lower QOL
      levels than the 'general population' in all NHP dimensions. The diet treatment
      group patients had lower QOL levels than the 'general population' only in the
      'Sleep' and 'Social isolation' dimensions. The diet group had a significantly
      better QOL level in all six dimensions of QOL of NHP than the tablet treatment or
      combined treatment (patients treated with tablets and insulin) groups. The tablet
      treatment and combined treatment groups did not differ significantly in any of
      the NHP dimensions. The logistic models testing the presence of at least one
      problem in the NHP dimensions showed that the number of other diseases increased
      the risk of having QOL problems in all dimensions and duration of the diabetes
      and the age of the patient had risk increasing effects in four NHP dimensions
      while the gender had only a small effect on the QOL in diabetic patients. The
      study shows that the NHP questionnaire as a general measure of the QOL reveals
      differences in the QOL between the different treatment groups and between
      diabetic patients and general population.

PMID- 9162618
TI  - Adult height and diabetic nephropathy.

PMID- 9162617
TI  - Chromium deficiency might contribute to insulin resistance, type 2 diabetes
      mellitus, dyslipidaemia, and atherosclerosis.

PMID- 9162619
TI  - Introduction of insulin therapy in the UK.

PMID- 9162620
TI  - The Cochrane Collaborative Diabetes Review Group.

PMID- 9162621
TI  - International Diabetes Epidemiology Group (IDEG)--Himeji Symposium. Genetic and
      life style factors in preventing diabetes--need for a new paradigm. Proceedings.
      Himeji, Japan, November 12-14, 1994.

PMID- 9162622
TI  - [Assessment of the hypothalamic-hypophyseal-adrenal axis in patients with chronic
      obstructive lung disease. Comparison of inhalant with systemic glucocorticoid
      therapy].
AB  - OBJECTIVE: The action of inhalation and systemic treatment of chronic obstructive
      pulmonary disease by suppressing the hypothalamo-hypophyseal-adrenal axis was
      compared in patients with chronic obstructive pulmonary disease (COPD). PATIENTS
      AND METHODS: Adrenocorticotropic hormone (ACTH) and cortisol concentrations were
      evaluated after a corticotropin-releasing-hormone (CRH)-test in 50 patients (aged
      43 +/- 14 years) with chronic obstructive pulmonary disease (COPD) receiving
      inhalant glucocorticoid treatment (IGC), 61 patients (aged 54 +/- 11 years) with
      COPD on systemic glucocorticoid treatment (SGC) and 50 healthy volunteers (32 +/-
      4 years). RESULTS: All 50 patients on IGC had normal CRH test results. 30 of 61
      patients with SGC had decreased cortisol response (12 patients had no and 18 a
      reduced rise in cortisol). ACTH concentration was lower in patients on IGC than
      in the control group (basal ACTH 15.6 pg/ml and 24.5 pg/ml, respectively; after
      stimulation 40.3 vs 54.4 pg/ml, respectively). But systemic glucocorticoid
      treatment clearly caused suppression of basal (12.1 pg/ml) and stimulated (27.4
      pg/ml) ACTH levels with correspondingly decreased cortisol levels (basal: 75.1
      and 118.7 ng/ml [IGC], respectively, and after stimulation 128.5 and 225.9
      ng/ml). CONCLUSIONS: Patients with COPD on inhalant glucocorticoid treatment have
      a clearly lower risk of adrenal cortical insufficiency than those on oral
      glucocorticoid treatment. But some suppression of ACTH secretion is demonstrable
      even in the former. Clinical significance of these findings seems unlikely.
      Development of adrenal cortical insufficiency need not be feared in patients
      treated with inhalant glucocorticoids.

PMID- 9162623
TI  - [Hereditary hyperferritinemia-cataract syndrome].
AB  - HISTORY AND FINDINGS: Symptom-free brother and sister of Italian descent (age: 31
      and 28 years), under examination to exclude haemochromatosis, were found to have
      increased serum ferritin levels. Both had cataracts removed, as had their mother.
      Physical examination had been normal in both siblings. INVESTIGATIONS: Serum
      ferritin levels were raised to 926 and 956 ng/ml, respectively, while blood and
      differential counts, blood sugar and serum iron levels, iron binding capacity and
      transaminases were within normal limits. Liver sonography was normal and biopsies
      excluded haemochromatosis in both cases. The serum ferritin levels were elevated
      in all family members who had a cataract. DIAGNOSIS: Family history, greatly
      elevated serum ferritin levels and cataracts established diagnoses of hereditary
      hyperferritinaemia-cataract syndrome. CONCLUSION: The autosomally inherited
      hyperferritinaemia-cataract syndrome is a new condition that should be included
      in the differential diagnosis of hereditary hyperferritinaemia. A single
      measurement of the serum ferritin level and ophthalmological examination are
      sufficient to make the diagnosis; liver biopsy is unnecessary and blood letting
      contraindicated, because it would quickly cause microcytic iron-deficiency
      anaemia.

PMID- 9162624
TI  - [Treatment of osteoid osteoma with CT-guided drilling and ethanol instillation].
AB  - HISTORY AND CLINICAL FINDINGS: For 6 months a 25-year-old man had been suffering
      from intermittent pain in the left upper leg, alleviated by aspirin. Physical
      examination was unremarkable: local pain was not elicited. INVESTIGATIONS:
      Routine radiology and computed tomography confirmed the clinically suspected
      diagnosis of intracortical osteoid osteoma of the femur. Skeletal scintigraphy
      showed distinctive local concentration of the contrast material. DIAGNOSTIC
      PROCEDURE, TREATMENT AND COURSE: The lesion's central area was identified by CT
      and under general anaesthesia drilled into (5 mm diameter drill bit). As the
      lesion's edges remained partially intact, the cavity was sterilized with 1-2 ml
      of 96% ethanol. The patient was mobilized after six hours. He has remained free
      of pain in the subsequent 7 months. CONCLUSIONS: Minimally invasive, CT-guided
      percutaneous treatment of an osteoid osteoma can be achieved by a combined
      radiological and percutaneous orthopaedic procedure as an alternative to open
      surgery.

PMID- 9162625
TI  - [Treatment of vaginal discharge].

PMID- 9162626
TI  - [Risk factors for pacemaker disorders].

PMID- 9162627
TI  - [The molecular mechanism of apoptosis. Report of the 4th European Conference on
      Apoptosis].

PMID- 9162628
TI  - [Again: Clause regarding physician substitutes in formal agreements on patient's
      choice. Verdict of the Bonn Regional Court, 20 June 1996].

PMID- 9162629
TI  - [Prostate-specific antigen in early detection of prostate cancer].

PMID- 9162630
TI  - Quality of life as an outcome measure in cancer clinical trials.
AB  - In the past decade, increasing attention has been given to more systematic and
      quantitative ways of evaluating explicitly the impact of diseases and medical
      interventions on quality of life. A substantial part of this research pertained
      to the field of cancer where cure is not always possible and treatments are
      mostly intrusive. This paper will address two broad issues. The first part
      focuses on the general issues related to the evaluation of quality of life, such
      as its concept, the purpose and design of the study and assessment criteria,
      particularly in the context of a cancer clinical trial. The second part focuses
      specifically on quality-of-life issues in urinary tract cancer.

PMID- 9162631
TI  - [The use of hypnosis in stomatology].
AB  - It follows from the fore going that hypnosis itself can not cure, but it is a
      great possibility to use it as a supplementary method and a curing means in our
      practice. The treatment is applicable for stomatological interventions, and
      somatic diseases of psychic origin which have connections on our field. Thus
      hypnosis can effect out therapeutic-work very favourable.

PMID- 9162632
TI  - [Use of an overdenture in the prosthetic correction in a patient with cleft
      palate].
AB  - A fourty-year old male patient with cleft palate had been operated on four times
      in his childhood in order to close the defect. The shrinked dental arch and the
      pseudoprogenia, remaining after the operation, caused problems in the mastication
      and esthetic defects to the patient. With the help of an overdenture a new dental
      arch was created, in this way the pseudoprogenia could be eliminated, the facial
      harmony and the mastication could be restored.

PMID- 9162633
TI  - [Oral gentic syndromes causing dental anomalies].
AB  - The author briefly described those genetic syndromes that are accompanied by
      tooth or dental arch anomalies. Some of these can be corrected by prosthetic
      means. These anomalies can be indications for prosthetic treatment.

PMID- 9162634
TI  - [Incidence and origin of dental pulp stones].
AB  - The authors found pulp stones in more teeth of a 12-years-old girl. The present
      work discusses the concerning literature and it establishes that these stones are
      traced back to different aetiological factors. Their role in the toothaces
      without caries and presence impeding at root treatment is also emphasized.

PMID- 9162635
TI  - [Developing subcutaneous emphysema after dental care].
AB  - Subcutaneous emphysema is a rare but potentially dangerous complication of dental
      and maxillofacial surgical interventions. The authors present three such cases
      and give an overview on the diagnostic, therapeutic and preventive possibilities
      of the disease.

PMID- 9162636
TI  - Dilemmas in family medicine education.

PMID- 9162637
TI  - Costs of teaching for community teachers of family medicine.

PMID- 9162638
TI  - Managing clinic time while precepting medical students.

PMID- 9162639
TI  - The 5-minute consult.

PMID- 9162640
TI  - Medical record completion: a consistent approach is the key.

PMID- 9162641
TI  - Validity of NBME family medicine exam questioned.

PMID- 9162642
TI  - [Dynamics of parameters of the functional activity of the thyroid gland and
      adrenal cortex during human adaptation to new ecologic conditions].

PMID- 9162643
TI  - [Peroxide-induced damage to high-density lipoproteins and their cholesterol
      acceptor function in patients with ischemic heart disease and in healthy people].

PMID- 9162644
TI  - [Normalizing effect of normobaric hypoxic hypoxia].

PMID- 9162645
TI  - [Dermatoglyphic patterns in Tourette syndrome].

PMID- 9162646
TI  - [Effect of afferent input from the motor apparatus on higher mental functions in
      children suffering from infantile cerebral palsy].

PMID- 9162647
TI  - [Is hypoxia a stimulus for structural and metabolic changes in skeletal
      muscles?].

PMID- 9162648
TI  - [Vasilii Iur'evich Chagovets--founder of the ionic theory of excitation (on the
      centennary of the creation of the diffusion theory of bioelectric phenomena)].

PMID- 9162649
TI  - [Decompression regimens for diving descents to a depth of 60 meters under medium
      altitude conditions].

PMID- 9162650
TI  - [Psychophysiological training of rhythmic regulatory nervous processes in
      patients with bronchial asthma].

PMID- 9162651
TI  - [New facts in the history of the doctrine of reflex control of the cardiovascular
      system].

PMID- 9162652
TI  - [Bioclimatic evaluation of mountainous territories].

PMID- 9162653
TI  - [Functional state of the temperature analyzer of operators in the gas
      condensation industry under conditions of hot climate].

PMID- 9162654
TI  - [Status of the cardiorespiratory system in representatives of various climato
      geographic regions during adaptation to to the hot climate of Central Asia].

PMID- 9162655
TI  - [Adaptation of the circulatory system to medium- and high-altitude hypoxia in
      heterozygous and homozygous adolescent twins].

PMID- 9162656
TI  - [Frequency range of the flicker fusion reaction in the cerebral cortex].

PMID- 9162657
TI  - [Electroencephalographic parameters of the functional state of the brain during
      representation of time intervals].

PMID- 9162658
TI  - [Features of hormonal status in aborigines of Northeast Russia as a function of
      the level of hypoxic resistance].

PMID- 9162659
TI  - [Effect of acclimatization to cold on the hypoxic sensitivity of the respiratory
      center].

PMID- 9162660
TI  - [Simulation of the effect of respiration on the amplitude of the T-wave of the
      electrocardiogram: theoretical and applied aspects].

PMID- 9162661
TI  - [Features of hormonal regulation of carbohydrate and lipid metabolism in people
      trained for conditions of immersion hypothermia].

PMID- 9162662
TI  - [Mechanism of action of temperature and chemical factors on the functioning of
      biological membranes].

PMID- 9162663
TI  - [Evaluation of the effect of global changes to the environment and climate on the
      qualitative potential of a population].

PMID- 9162664
TI  - [Medico-biological aspects of a Mars expedition].

PMID- 9162665
TI  - [Adaptation of the cardiovascular system in adolescents].

PMID- 9162666
TI  - [Medico-physiological aspects of individually differentiated teaching of senior
      pupils].

PMID- 9162667
TI  - [The use of a check list for quality assurance of the treatment of acute
      myocardial infarction in the coronary care unit].
AB  - The implementation of Quality Assurance programs for the treatment of acute
      myocardial infarction in the Cardiac Intensive Care Unit may be specially
      important. In fact several therapeutic options are available in these patients,
      and delay in treatment must be as short as possible. A Quality Assurance program
      has been started in our center with a registry of all patients admitted within 24
      hours of onset of acute myocardial infarction. PATIENTS AND METHODS: The
      following data were recorded: 1) indicators of Organization: pathway to
      admission, pre-hospital and in-hospital delay; 2) Process Indicators: duration of
      hospital stay, initial choice of therapy (conservative, intravenous lysis,
      primary angioplasty), and further diagnostic and interventional procedures; 3)
      Outcome Indicators: mortality and complications during admission, and 6-12 months
      follow-up. RESULTS: Since february 1994 to August 1995, 211 consecutive patients
      were included in the registry; 156 were male, mean age 66 years. Mean pre
      hospital delay was 286 minutes. Admission was decided by a physician in 99 cases
      and by the patient him/herself in 112 cases; pre-hospital delay was 390 min. In
      the former group, and 194 min. In the latter (p < .001). Mean in-hospital delay
      was 61 minutes. Conservative treatment, intravenous lysis, and primary
      angioplasty were chosen by the attending cardiologist in 89 patients (group A),
      69 patients (group B), and 53 patients (group C) respectively. The latter group
      included patients with highest risk on the basis of clinical and
      electrocardiographic characteristics. In-hospital mortality was 17, 7 and 9% In
      the 3 groups, respectively. An echocardiogram and coronary angiography were
      performed before discharge in 81% and 57% of patients, respectively. The mean
      duration of hospital stay was 11 days, irrespective of the initial therapeutic
      choice. CONCLUSIONS: A registry for patients with acute myocardial infarction
      provides information which is essential in the evaluation of therapeutic
      protocols; it may also help in improving the cooperation between the Emergency
      Department, the attending cardiologists, and the family physicians.

PMID- 9162668
TI  - [Short and intermediate term clinical outcome in patients with cardiogenic shock
      treated with aortic counterpulsation].
AB  - BACKGROUND: Despite improvements in coronary care, cardiogenic shock (CS) remains
      the leading cause of death in patients with dramatic cardiac diseases of which
      acute myocardial infarction (AMI) is the most frequent event. Conventional
      therapy for CS with coronary care unit (CCU) monitoring and vasopressor agents to
      support blood pressure has historically been associated with an 80% to 90%
      mortality rate in large series. Intra-aortic balloon pump (IABP) therapy for
      shock results in initial favourable clinical and haemodynamic responses, but
      ultimately, in most patients, death is merely delayed and hospital mortality
      still exceeds 80%. In several recent non-randomised series, coronary
      revascularisation performed early in the course of CS with the use of coronary
      artery by-pass grafting (CABG) or coronary angioplasty (PTCA) resulted in an
      apparent reduction in the hospital mortality rate to less than 50% in selected
      patients with shock. OBJECTIVES: This study reviews our experience of cardiogenic
      shock treatment at a time when standard care included aggressive use of the intra
      aortic balloon pump counterpulsation, cardiac catheterisation, coronary
      angioplasty and/or coronary artery by-pass grafting, ventricular septal defect
      and mitral incompetence repair. METHODS: We retrospectively analysed 20 patients
      (13 M and 7 F, with an average age of 62 years and a half) affected by
      cardiogenic shock consecutively admitted to our CCU between October 1, 1992 and
      April 1, 1995. Fifteen patients (pts) were hospitalised for AMI, shock and pump
      failure (2 of them with pulmonary oedema), all with admittance delay less than 24
      hours. Five patients were hospitalised for AMI with shock and mechanical defects,
      of which 3 pts with AMI and ventricular septal rupture and 2 pts with AMI and
      mitral regurgitation. All patients underwent IABP, coronary angiography (CA) and
      then were treated with PTCA, CABG and cardiac surgery or medical treatment.
      RESULTS: On the whole, 7 pts died (35%): 4 of shock, 1 of haemorrhagic
      complications, 1 of septic shock in the CCU, and 1 of heart failure after CABG in
      cardiosurgery. One more patient died of heart failure two months after discharge
      (late mortality 5%). Out of the 15 patients hospitalised with AMI, shock and pump
      failure, 13 patients with AMI and CS less than 24 hrs were treated as follows: 1
      patient was successfully submitted to emergency CABG and 12 patients to PTCA of
      the infarct related artery (IRA). Eight patients enjoyed a good outcome, but 1
      patient died of haemorrhagic complications and 4 with a persistently occluded IRA
      also died (3 in the CCU and 1 after CABG). Of the 2 remaining pts with AMI, shock
      and pulmonary oedema, 1 patient underwent CABG with success and 1 patient with
      the 3-vessel disease was submitted to PTCA with reperfusion of the IRA, but he
      died from reocclusion three days later. Out of the 5 patients with AMI, shock and
      mechanical defects, 3 patients with AMI and septal ventricular rupture underwent
      cardiac surgery and CABG with early and late success. One of the 2 patients with
      AMI, shock and mitral regurgitation underwent cardiac surgery with valve repair
      and CABG and had a good outcome, the other died from septic complications in the
      CCU. CONCLUSIONS: IABP is an useful device for stabilising patients in
      cardiogenic shock and safely performing angiography as well as PTCA, CABG or
      surgical correction of all mechanical complications with a more stable
      haemodynamic balance. Therefore, IABP is an useful tool to improve successful
      coronary revascularisation after direct PTCA or direct CABG. These data also
      suggest that the combination of successful coronary revascularisation and intra
      aortic balloon pumping can improve survival in pts with cardiogenic shock
      complicating AMI with early pump failure.

PMID- 9162669
TI  - [ST segment depression during recovery after treadmill exercise test in stable
      patients with previous myocardial infarction].
AB  - BACKGROUND: The significance of exercise-induced ST segment depression is well
      known while limited data are available on the clinical/prognostic power of ST
      depression occurring only during recovery. Aim of the study was to clarify the
      clinical/prognostic value of "recovery only" ST depression in stable patients
      late from myocardial infarction (AMI) and to determine whether the addition of
      recovery data to exercise parameters improves the interpretation of exercise
      test. METHODS: From a population of 766 consecutive patients (mean age: 57.2 +/-
      8.6 yrs.; male: 89%) who underwent a Bruce Treadmill test at least 1 year after a
      Q wave AMI and whose exercise data were prospectively entered in the database of
      our Institution, 4 different Groups were identified: 1) 99 patients with a
      negative exercise test; 2) 53 patients with "exercise only" ST depression; 3) 140
      patients with "exercise and recovery" ST depression; 4) 31 patients with
      "recovery only" ST depression. The main clinical and exercise data and a cardiac
      follow-up (average mean length: 1530 +/- 600 day) were evaluated by one-way
      analysis of variance, Bonferroni T-test, chi-square, relative risk (RR) with 95%
      confidence intervals (CI), Kaplan-Meler method and log-rank. RESULTS: Baseline
      clinical parameters were similar in the 4 Groups except for older age in Group 3
      compared to Group 2 (< 0.05) and higher prevalence of anterior AMI in Group 4
      compared to others (= 0.004). Patients with exercise and recovery ST depression
      or with "recovery only" ST depression had significantly less exercise tolerance
      than patients with negative exercise test or "exercise only" ST depression
      [exercise duration (< 0.05, Group 1 vs. 3, vs. 4; Group 2 vs. 3), peak rate
      pressure product (< 0.05), maximal heart rate (< 0.05; Group 1 vs. 2; vs. 3; vs.
      4)]. Exercise-induced ST depression was higher and angina was significantly more
      frequent in patients with exercise and recovery ST depression as well as an high
      Mark's risk score (< 0.001). Only patients with exercise and recovery ST
      depression demonstrated significantly higher risk of overall mortality (RR: 1.35,
      CI: 1.04-1.74), unstable angina (RR: 1.34, CI: 1.09-1.65) or revascularisation
      procedures (RR: 1.51, CI: 1.25-1.83). Relative risk of patients with "recovery
      only" ST depression was similar to that of subjects with "exercise only" ST
      depression. CONCLUSIONS: In stable patients with old Q wave AMI, "recovery only"
      ST depression is rate, but does represent a true sign of ischemia. It could be
      associated with indirect indexes of worse ventricular function. The prognostical
      power of "recovery only" ST depression is mild, although similar to that of
      "exercise only" ST depression. Moreover the presence of ST depression not only
      during exercise but also during the recovery phase identifies patients with more
      severe prognosis. Therefore the inclusion of findings from the recovery phase in
      the analysis of the exercise test could increase the predictive power of the test
      itself.

PMID- 9162670
TI  - [Sudden death from lipomatous hamartoma of the heart].
AB  - The authors report a case of a patient arrived at their observation in
      cardiogenic shock. The ECG showed extreme bradycardia refractory to resuscitation
      manoeuvres. The autopsy showed a lipomatous hamartoma in the interatrial septum.
      The lipomatous hamartoma is a primitive cardiac tumor, very rare, with an usually
      asymptomatic course but with severe prognosis. The authors emphasize that
      clinical presentation can be aspecific and resembling several other diseases, and
      early identification can be achieved only by 2D echo-cardiography or nuclear
      magnetic resonance imaging.

PMID- 9162671
TI  - [Modified technique for dilatation of pulmonary valve stenosis (nearly atresia)
      in a neonate].
AB  - A modified technique for pulmonary valvuloplasty is described in a 1-day-old
      newborn with near pulmonary atresia. A transumbilical venous approach and a
      complete set of devices for coronary angioplasty were utilized; the principal
      technical innovation was the use of a 7 French right coronary artery guiding
      catheter. This allowed a firm support to advance the first balloon catheter (a
      3.5 coronary angioplasty catheter) through the pulmonary valve, maintaining the
      guidewire in a stable position in the descending aorta. The dilation was easily
      completed with progressively larger balloons. The total procedure time was 82'
      (fluroscopy time 20'), significantly shorter than the previous personal
      experience and the data from the literature.

PMID- 9162672
TI  - [Aberrant papillary muscle causes wall motion alterations: diagnostic
      implications].
AB  - We report a case of 77 year old man who never complained cardiac symptoms, with
      progress septal myocardial infarction diagnosed by electrocardiographic signs and
      akinesia of the septum-apical segment, detected by echocardiography. He underwent
      a new echocardiographic examination that pointed out an aberrant papillary muscle
      in the left ventricle which base (19 mm) was situated on the middle of the
      anterior-septum and apex connected with the apical portion of the lateral wall,
      inducing a dissinergic movement of the septum-apical segment as for the adjacent
      wall segments and with a reduced sistolic thickening. An exercise myocardial
      perfusion scintigraphy (Tl 201) detected no reversible or irreversible uptake
      defects, continuous ecg monitoring and an exercise test did not show any ischemic
      event. We discuss the electrogenetic and wall motion implication due to an
      aberrant papillary muscle that can be errorly considered secondary to a progress
      myocardial infarction.

PMID- 9162673
TI  - [Acute myocardial infarction in pregnancy in a patient with pseudoaneurysm of the
      left main coronary artery].
AB  - Myocardial infarction during pregnancy is a rare event and it can be associated
      both with obstructive coronary artery disease and with functional conditions such
      as vasospasm. We report a 28-year-old woman without coronary artery disease risk
      factors, who suffered a Q infarction at 38th week of gestation, complicated by
      ventricular fibrillation. A healthy child was delivered by cesarean section and
      the woman made a full recovery. A coronary pseudoaneurysm was detected
      angiographically, suggesting an initial spontaneous coronary artery dissection
      followed by ectatic evolution. Coronary dissection associated with coronary
      vasospasm should be kept into account as etiopathogenetyc mechanisms of acute
      myocardial infarction.

PMID- 9162675
TI  - Assessment of coronary artery anatomy and function by MRI.

PMID- 9162674
TI  - [Transesophageal echocardiographic evaluation of tricuspid endocarditis from
      implanted pacemaker: description of two cases].
AB  - Two cases of tricuspid valve endocarditis due to staphylococcus epidermidis have
      been examined in patients with permanent transvenous pacemaker. While
      transthoracic echocardiography was unable to detect any tricuspidal
      abnormalities, large vegetations located on the tricuspidal leaflets and the
      electrocatheter were detected by transesophageal echocardiography. Both cases
      required surgical removal of the electrostimulation system and valve toilet.

PMID- 9162676
TI  - [Cardiomyoplasty. Critical review of experimental and clinical results].
AB  - Cardiomyoplasty (CMP) is a surgical therapy for dilated cardiomyopathy. In this
      procedure the "latissimus dorsi" is wrapped around the heart and chronically
      paced synchronously with ventricular systole. CMP has been performed in more than
      500 cases worldwide, 42 cases in Italy, with variable degrees of success. Despite
      symptomatic improvement in the majority of patients surviving the procedure,
      objective hemodynamic effects have not been consistently demonstrated. The
      hemodynamic effect of CMP has been the subject of a great deal of experimental
      and clinical research over the past decade. This article discusses in detail the
      published results of experimental and clinical cardiomyoplasty, with particular
      emphasis on hemodynamic effects and limitations of the procedure.

PMID- 9162677
TI  - [Lipid factors and evolution of the atherosclerotic plaque: review of recent
      trials].
AB  - A beneficial impact of lipid-lowering therapy on the incidence of coronary artery
      disease has been demonstrated in several clinical trials. It has been suggested
      that lipid lowering therapy not only slows the progression of atherosclerotic
      lesions, but also promotes its regression. Furthermore, reduced levels of
      circulating cholesterol (total cholesterol as well as LDL fraction) might
      decrease plaque volume and growth, restore endothelial function and thus reduce
      vasomotor tone. The obtained increased plaque stability reduces the risk of
      disruption and subsequent cardiovascular events. Ongoing ultrasonographic and
      angioscopic studies will provided further insights into the disease itself and
      its management.

PMID- 9162678
TI  - [Microvascular function and regulation of coronary blood flow in ischemic
      cardiomyopathy].

PMID- 9162679
TI  - [New aspects in the evaluation of cardiologic fitness in sport activities. From
      the Bethesda Conference in 1994 to the Italian COCIS in 1996. Cardiologic
      Organizational Committee for Cardiovascular Fitness in Sport].

PMID- 9162680
TI  - [A mitochondrial portrait of Eastern Slavs].
AB  - Data on polymorphism of the control region of mitochondrial DNA (mtDNA) in
      Eastern Slavs were analyzed by the median network method. A bimodal distribution
      of pairwise nucleotide differences between types of the mtDNA control region was
      revealed; distribution was similar to that found in southern European
      populations. The nucleotide diversity of mtDNA types in Eastern Slavs
      corresponded to an evolutionary age of 10-40 thousand years. Characteristics of
      the mitochondrial portrait of Eastern Slavs are discussed in terms of formation
      of the European population in Neolith.

PMID- 9162681
TI  - [Detection of frequent mutations of the CFTR gene in cystic fibrosis patients
      from Central Russia].
AB  - About 100 patients with cystic fibrosis (CF) from the European part of Russia
      were screened for mutations 2143delT, 2184insA, S1196X, 3732delA, and W1282X. The
      patients had one or two mutations (other than delta F508) in CF chromosomes. The
      frequency of these mutations were estimated in CF chromosomes without the delta
      F508 mutation. The frequencies of mutations 2143delT, 2184insA, S1196X, and
      W1282X were 2.9, 7.4, 2.2, and 4.8%, respectively. Linkage was found between
      allele 6 of the variable site (a tetranucleotide repeat in intron 6 of the gene
      for CF) and mutations G542X and 2143delT, as well as between allele 7 and
      mutations R334W, 2184insA, S1196X, and W1282X. Except for delta F508, the most
      common mutations were 2184insA, 2143delT, and W1282X.

PMID- 9162682
TI  - [Effect of genotype on the relationship between parameters of intelligence and
      cognitive style].
AB  - The roles of genetic and environmental factors in regulating parameters of
      intelligence and cognitive style were studied. Monozygotic and dizygotic twins
      were tested three times, at the ages of 6, 7, and 10 years. The Wechsler
      Intelligence Test, Embedded Figures Test, and Matched Figures Fitting Test were
      used. Interrelations between the Intelligence Quotient and cognitive style
      appeared to be Independent of the shared regulatory mechanisms. Genetic
      correlations between IQ and cognitive style indicate that they are influenced in
      part by shared and nonshared genetic factors. It is proposed that qualitative
      changes in psychological features associated with the dynamic features of
      cognitive activity occur at the age of 7 years.

PMID- 9162683
TI  - [Effect of exogamy on morbidity among children during the first three years of
      life].
AB  - The incidence of common diseases among children in the first three years of life
      was studied in relation to the degree of outcrossing in family history, the level
      of education of both parents, and the age of entering nursery school. A total of
      526 children (274 boys and 252 girls) were inspected. The factors under study
      proved to have no effect on morbidity among children under one year of age.
      However, morbidity during the second and third years of life depended on the
      degree of outcrossing in the children's family background, the educational level
      of their mothers, and the age of their entrance into nursery school. Higher
      morbidity at this age was characteristic of children born of parents belonging to
      different ethnic groups, and this situation was independent of social factors.
      The role of genetic coadaptation and epistasis in determining the relationship
      between outcrossing and morbidity is discussed.

PMID- 9162685
TI  - [Recombination in Drosophila melanogaster males exposed at a thermoelectric power
      plant].
AB  - For four years, genetic recombination was studied in Drosophila melanogaster
      males kept at a thermoelectric power station (TPS) in Moscow; a TPS located in
      another city district was taken for comparison in 1994. It was found that, in the
      experimental males, recombination frequency was two- to threefold higher than in
      the control flies. Temporal variations in recombination frequency during four
      years were not statistically significant. The data obtained at the two TPSs also
      did not significantly differ from each other. The considerable increase of the
      recombination frequency in Drosophila kept at the TPS may be considered an
      appropriate response to exposure to effective mutagens that were abundant in the
      TPS discharges.

PMID- 9162684
TI  - [Molecular analysis of a copy of the novel mobile element Burdock and the region
      of its insertion into the cut locus of Drosophila melanogaster].
AB  - Molecular analysis of a copy of the novel mobile element burdock and its
      insertion region into the cut locus of Drosophila was performed. The burdock was
      shown to be a retrotransposon containing a single open reading frame (ORF). It
      does not contain domens coding for protease, RNAse H, reverse transcriptase, and
      integrase, which are required for transposition. However, multiple insertions of
      this copy of the mobile element into a definite region of the cut locus (hot
      site) were observed earlier. The polypeptide encoded by the burdock ORF contains
      two successive regions homologous to the proteins encoded by the ORF1 and ORF2 of
      the gypsy retrotransposon in N and C regions, respectively. The burdock insertion
      into this region of the cut locus interrupts its ORF, since the mobile element is
      transcribed in the opposite direction compared with the transcription in the
      locus. This is presumed to account for the arising of a lethal mutation. The hot
      site of this element integration into the locus corresponds to the recognition
      site of Drosophila topoisomerase II.

PMID- 9162686
TI  - Unique chromosome rearrangements in karyotypes of yellow-necked mice (Apodemus
      flavicollis) from various populations.
AB  - Cytogenetic monitoring of yellow-necked mouse populations in various parts of the
      species range revealed deviations from the standard chromosome set in two
      individuals (Female from the Bryanskaya region and Male from the Samarskaya
      region). In both of them the wholly acrocentric chromosome set was supplemented
      by a large unpaired submetacentric chromosome. The C-banding showed no structural
      homology between these newly formed chromosomes. Obviously, they had been
      produced by different mechanisms, which may include amplification of
      paracentromeric heterochromatin in a large chromosome (Female) and classical
      Robertsonian fusion of two acrocentrics (Male). The low frequency and
      nonhomologous state of these rearrangements suggest their mutational origin.

PMID- 9162687
TI  - [Molecular genetic nature of mutations at the white locus, induced by chemical
      substances in Drosophila melanogaster].
AB  - Molecular genetic mechanisms of the white mutations induced by mitomycin C, N
      ethyl-N-nitrosourea, and ethidium bromide were studied. Genomic DNA of the
      original strain and mutants obtained was tested by Southern blot hybridization.
      The presence of mobile genetic elements was shown to be characteristic of the
      white locus of the original strain. Mutations of the white gene obtained mainly
      resulted from excision of DNA sequences involving mobile genetic elements and
      insertion of unidentified 5-6-kbp DNA fragments.

PMID- 9162688
TI  - [Genomic variation of laboratory strains and natural populations of Drosophila
      melanogaster exposed to X-irradiation].
AB  - The spontaneous and X-ray-induced mutation rates and spectrums were estimated in
      laboratory strains and natural populations of Drosophila melanogaster from the
      Chernobyl meltdown area. Laboratory strains Oregon R and y2w alpha 4 were stable.
      In all natural populations, the spontaneous mutation rate was an order of
      magnitude higher (10(-3)) than in laboratory strains. Irradiation at a total dose
      of 3000 R was shown to induce genetic instability in the stable laboratory strain
      y2w alpha 4 and to increase the mutation rate and spectrum range in the unstable
      natural population P1. A high level of genetic instability was observed both in
      the first and second generations. Genetic analysis by means of classical genetic
      and molecular methods was performed; in crosses, a collection of spontaneous and
      induced mutants was used. The molecular genetic nature of mutations at the white
      and cut loci was analyzed by Southern blot-hybridization. Mutations at the white
      locus were shown to result both from transposition and recombination events; cut
      mutations were caused by deletions.

PMID- 9162689
TI  - [Homology and evolution of gene orders: simulation and reconstruction of the
      evolutionary process].
AB  - A method to reconstruct the evolutionary history of observed gene orders from
      estimates of their similarity has been developed. It was shown that similarity
      measures accounting or not accounting for gene order in linkage groups of the
      compared genomes can be used for this purpose. A number of plausible variants of
      gene-order evolution from the common ancestral form in seven primate species were
      obtained.

PMID- 9162690
TI  - [Genetic differentiation and phylogenetic relationships among Palearctic mice
      (Rodentia, Muridae)].
AB  - Genetic differentiation of 18 Palearctic mouse species (genera Sylvaemus, Mus,
      Apodemus, Micromys, and Rattus) with respect to 31 biochemical loci was estimated
      to define the taxonomic status of these genera. On the basis of genetic data, two
      independent centers of origin of species belonging to the family Muridae were
      identified. The first is the Indo-African center, from which the modern Sylvaemus
      species and Palearctic representatives of Mus originated in the Pleistocene (1.0
      2.0 million years ago). Genera Micromys and Apodemus, which diverged in early
      Pliocene (about 7 million years ago), trace their origin to the same center. From
      the second center, located in Southeast Asia, Rattus species radiated. The
      genetic divergence of taxa issuing from these two centers attains the level
      characteristic of differentiation between families and dates back to the late
      Miocene (over 10 million years ago). Species were compared pairwise to determine
      the percent of fixed gene differences (Pfd) between them. Analysis of Pfd
      distribution confirmed distinct periodicity of speciation in mice and revealed
      two speciation peaks. The first, at the level of genera, occurred in the
      Pliocene, and the second, at the species level, in the Pleistocene.

PMID- 9162691
TI  - [Features of the distribution of BoLA-A antigens and alleles of the BoLA-DRB3
      gene in Black Pied cattle in relation to association with leukemia].
AB  - The character of distribution of BoLA class-I antigens was studied in Black Pied
      cattle populations differing in status in relation to leukemia. Associative
      relationships of distinct antigens with resistance and susceptibility to leukemia
      were revealed. Using the statusmetria method, an integral estimate of
      predisposition to leukemia (Z) was calculated taking into consideration the
      contribution of each antigen in the immunogenetic status of the animal. The
      interval of Z values was determined, which allowed animals to be divided into
      groups according to resistance or susceptibility to leukemia. Alleles of the BoLA
      DRB3 gene were typed in subsamples of animals with leukemia and healthy animals
      by the PCR-RFLP method. Twenty alleles of the gene were detected, and their
      frequencies were determined in both subsamples. Alleles mediating resistance of
      animals to leukemia (BoLA-DRB3.2*11, *23, and *28) were distributed in the group
      of healthy animals with frequencies of 0.079, 0.132, and 0.053, respectively;
      they were completely absent in animals with leukemia. The data on the estimate of
      animal status in relation to leukemia, which were obtained by the method of
      statusmetria taking in consideration the real contribution of the each class-I
      antigen in the detection of the disease risk (value Z), and data of allele typing
      by the PCR-RFLP method were shown to be in good agreement. The possibility of
      using BoLA class-I antigen typing in herds to determine the number of animals
      with leukemia was demonstrated.

PMID- 9162692
TI  - [Restriction polymorphism of the proto-oncogene c-Ha-ras-1 in patients with
      multiple primary malignant neoplasms and non-small-cell lung cancer].
AB  - Restriction fragment length polymorphism in the human c-Ha-ras-1 locus,
      associated with a minisatellite sequence, was examined in 45 multiple primary
      cancer (MPC) patients, 56 patients with squamous cell lung cancer (SCLC), 21
      patients with lung adenocarcinoma (LAC), and 53 individuals having no
      oncopathology. Southern analysis of cellular DNA revealed the presence of 4
      common alleles (with collective allele frequency close to 94% in the control
      group) and a set of rare alleles. Allele a3, (2.1 kb in size under MspI/HpaII
      digestion) was shown to be more frequent in the MPC than in the control group.
      The same tendency was observed in the patients with highly differentiated cell
      lung cancer. An increased frequency of the a4 allele (2.5 kb under MspI/HpaII
      digestion) was observed in the patients with adenocarcinomas as well as in the
      patients with metastases and low levels of tumor tissue differentiation. The
      elevated frequencies of a3 in the MPC group and of a4 in the LAC patients did not
      correlate with increased risk of the cancers mentioned above but was associated
      with type of tumor progression. Previously, it was reported that the mini
      satellite sequence within the c-Ha-ras-1 locus possesses enhancer activity. Our
      data indirectly confirm the hypothesis that the efficiency of minisatellite
      modulator activity is associated with fragment size.

PMID- 9162693
TI  - [Mutagens and antimutagens in food products].
AB  - Probable pathways of food contamination with environmental chemical mutagens and
      factors responsible for the formation of mutagens in food during cooking are
      reviewed, and natural and synthetic food components with mutagenic properties are
      described. The data discussed provide evidence for the expediency of further
      analyzing mutagenicity of various food components and developing chemical
      analytical methods for their detection and identification. Antimutagenic
      compounds present in food are characterized. The adequacy of methods for
      estimating the activity of these compounds and perspectives for their use as
      antimutagenic chemopreventive agents are discussed. Emphasis is placed on the
      necessity of being extremely cautious in employing food antimutagens because of
      the probable inversion of their effects. Several examples are provided to
      demonstrate the possibility of reducing mutagenicity of prepared food by
      modifying food processing technology.

PMID- 9162695
TI  - [Attachment of polytene chromosomes to the nuclear envelope in ovarian
      pseudonurse cells in Drosophila melanogaster].
AB  - Certain aspects of the polytene chromosome attachment to the nuclear envelope
      (NE) of ovarian pseudonurse cells (PNC) in the mutant strains otu11 and fs(2) B
      of Drosophila melanogaster were studied. In contrast to salivary a local
      chromocenter and Rable-orientation of chromosomes were shown to be missing from
      the PNC nuclei. The pericentric regions were scattered in the nuclear space and
      were obliged to attach to the NE by specific loci of heterochromatin. These loci
      were assigned to the regions 20CD and 41, and the proximal regions 81 and 101 of
      the cytological map of secondary polytene chromosomes. Each of the loci, which
      was obliged to attach to the NE, had a specific morphology that was similar in
      the otu11 and fs(2)B strains. PNC were shown to resemble normal ovarian nurse
      cells of D. melanogaster in the position of the polytene chromosomes and their
      attachment to the NE.

PMID- 9162694
TI  - [Genotoxic effect of cadmium chloride in various test-systems].
AB  - Many industrial regions of Bulgaria are contaminated with cadmium. Induction of
      various genetic damages by four concentrations of cadmium chloride was studied in
      various test systems. None of the tested concentrations induced gene mutations in
      Salmonella typhimurium. An increase in frequency of gene mutations, mitochondrial
      mutations, and intragene recombination was detected in Saccharomyces cerevisiae
      treated with the highest cadmium chloride concentration. A clastogenic effect and
      a significant decrease in mitotic index (MI) were induced in radicle meristem
      cells of Pisum sativum L. by the two highest cadmium chloride concentrations.
      Cadmium chloride was also shown to increase the frequency of sex-linked recessive
      lethals (SLRLs) and dominant lethals (DLs) in Drosophila germ cells. The results
      obtained in different test systems allow cadmium chloride to be considered a weak
      mutagen inducing various genetic damages.

PMID- 9162696
TI  - [Chromocenter organization in salivary glands of the malaria mosquito Anopheles
      messeae Fall].
AB  - The chromocenter organization and the relationship with the nuclear envelope were
      studied in Anopheles messeae Fall. malaria mosquito. The interchromosomal
      contacts within the chromocenter were shown to be formed by both alpha- and beta
      heterochromatin. In the pericentric regions of all chromosomes and in highly
      repeated sequences localized mostly in alpha-heterochromatin, the incorporation
      of the moderate He-T repeat of D. melanogaster was also found. Each chromosome
      was shown to have an independent contact to the nuclear envelope via certain beta
      heterochromatin loci. The morphology of the Y chromosome, which is also capable
      of forming ectopic contacts within the chromocenter boundaries, was studied.

PMID- 9162697
TI  - [Genetic control of the stress response of the system of juvenile hormone
      metabolism in Drosophila virilis].
AB  - Metabolism of juvenile hormone (JH) in 11-day-old D. virilis flies from resistant
      and sensitive lines and in hybrids of these lines was analyzed after short-term
      heat stress (4 h, 38 degrees C). The level of JH hydrolysis after stress remained
      constant in the sensitive line, but drastically decreased in the resistant one.
      Between-line differences of the metabolic JH response to stress were shown to be
      controlled monogenically or by a block of closely linked genes. The allele of the
      resistant line was dominant.

PMID- 9162698
TI  - [Selective expression of a mutation of the rad 201 radiosensitivity gene in
      Drosophila embryogenesis].
AB  - Embryonic sensitivity to the lethal effect of gamma-irradiation was compared in a
      radiosensitive mutant strain rad201G1 and a control radioresistant strain of
      Drosophila during the first 9 h of embryonic development. Embryonic
      radiosensitivity was analyzed with regard to the physiological age of embryos at
      the time of exposure to radiation. In the wild-type embryos, age-dependent
      variations of radiosensitivity were shown to be closely associated with
      genetically determined alterations in mitotic cycle structure, synchronism, and
      duration of separate phases. The rad201 gene mutation, which disrupts repair of
      chromosome damage in female germ cells and somatic cells of Drosophila, is
      expressed selectively during the period studied. The mutation had no effect on
      lethality at the stages of cleavage division, which represent alternations of S
      and M phases of the cell cycle. However, it caused an increase in lethality at
      the stage of postblastodermal mitotic divisions, whose onset is associated with a
      transformation of the organization and functions of genetic material and the
      appearance of G2 in the cell cycle. This transformation seems to be required for
      the functioning of the repair system affected by rad201.

PMID- 9162699
TI  - [A prolonged maternal effect of the rad201 radiosensitivity gene in Drosophila].
AB  - To study the maternal effect of the rad201 gene, sensitivity to the lethal effect
      of ionizing radiation was tested during Drosophila embryogenesis. Lethality
      induced by gamma-rays was analyzed in progeny of reciprocally crossed females and
      males, homo- and heterozygous at gene mutation rad201G1 controlling
      radiosensitivity. No effect of the maternal genotype was detected during cleavage
      division. However, the effect was pronounced at the stage of postblastodermal
      mitotic division: progeny of heterozygous females were significantly more
      radioresistant than progeny of homozygous females. When studying the survival of
      pupae developed from larvae exposed to radiation, the maternal effect of the wild
      type allele of the rad201 gene was shown to persist throughout the total larval
      stage. The frequency of morphoses of wings, chaetae, and abdominal tergites was
      also studied in adults that developed from larvae exposed to radiation at the
      late instar. The maternal effect was significant for abdominal morphoses
      resulting from the death of imaginal histoblasts. The frequency of abdominal
      morphoses was four times higher in progeny of females homozygous for the mutation
      than in progeny obtained from reciprocal crosses. Since radiation-induced damage
      of imaginal histoblasts is critical for pupal survival, these cells can be
      assumed to determine the prolonged maternal effect of the rad201 gene at the
      postembryonic stage of the Drosophila life cycle.

PMID- 9162700
TI  - [Ethnogenetics of the Komi-Zyrians according to data on the distribution of gene
      frequencies of erythrocyte and serum systems in the blood].
AB  - Distribution of gene markers of blood groups (ABO, RH, MN, KEL, and FY),
      erythrocyte enzymes (SOD-A and 6-PGD) and serum proteins (Hp, Gc, Tf, and ChE2)
      was studied in 10 ethnographic and geographic groups of Komis. Some of the groups
      studied differ significantly in the allele frequencies--B-ABO (0.163-0.289), Fy
      alpha (0.496-0.693), K (0.018-0.076)--and in haplotype frequencies of RH system-
      CDe (0.237-0.403), cDE (0.219-0.351), and cde (0.225-0.425). Average gene
      frequencies in Komis are considered in regard to ethnogenesis of the nation. It
      is demonstrated that Komis are genetically close to Finno-Ugrian ethnic groups of
      the Ural territory, but are different from Baltic Finns.

PMID- 9162701
TI  - [A new PCR-primer for specific amplification of human DNA fragments selected on
      the basis of computer analysis of the nucleotide sequences of MER1 dispersed
      repeats in man].
AB  - The possibility of using oligonucleotides from MER1 family repeats as PCR primers
      for the amplification of human genome DNA fragments was studied. The recommended
      oligonucleotide primers were chosen by computer analysis of the data base of the
      EMBL (release 37.0) nucleotide sequences. Use of one of the oligonucleotides was
      shown to allow specific human DNA amplification to be carried out.

PMID- 9162702
TI  - [Effect of interbreeding on the variability of anthropometric traits at birth and
      the variability of polymorphic genes].
AB  - Effects of outbreeding on variation of four anthropometric traits--body weight,
      body length, and circumferences of head and chest--and variability of seven
      polymorphic loci coding for blood proteins--HP, GC, PGD, GLO1, ESD, ACP, and PGM1
      -were studied. A total of 514 infants (271 boys and 243 girls) were examined. On
      the basis of pedigree analysis, two groups were formed: infants from monoethnic
      families (N = 363) and those from multiethnic backgrounds (N = 151). The two
      groups did not differ significantly with respect to the mean values and variances
      of the four anthropometric traits, but the coefficients of correlation between
      the traits among outbred newborns were higher than those for newborns from
      monoethnic families. The heterozygosity of the offspring of interethnic marriages
      was insignificantly higher than that of purely Russian infants. However, the
      linkage disequilibrium calculated for all possible pairwise combinations from the
      seven polymorphic loci was substantially higher in the offspring of interethnic
      marriages. The data obtained confirmed an earlier suggestion that outbreeding
      enhanced epistatic gene interaction in human populations.

PMID- 9162703
TI  - [TUB9 polymorphism in the CFTR gene of cystic fibrosis patients, carriers, and
      healthy donors from the Moscow region. SSCP and restriction analyses].
AB  - Data on the screening of 266 non-delta F508 chromosomes (42 cystic fibrosis
      patients, 43 carriers, and 48 healthy donors from the Moscow region) for the
      presence of structural abnormalities within the tenth exon of the CFTR gene
      conducted by means of the single-stranded conformation polymorphism (SSCP)
      technique in nonisotope modification are presented. The method used made it
      possible to detect three SSCP variants, one of which was present in cystic
      fibrosis patients (23.8%) and carriers (9.3%), but not in healthy donors.
      Sequencing of the 5 amplified DNA fragments carrying this SSCP variant revealed
      an A-->G substitution in the 1525-61 position, which indicated the presence of
      TUB9 polymorphism with allele 1 in the homozygous state in all cases tested. The
      three SSCP variants described corresponded to the three allelic variants of TUB9
      polymorphism as judged by MnlI restriction analysis of the amplified tenth exon
      sequence. The modified SSCP technique is also suitable for routine screening for
      the G542X, G55ID, and W1282X point mutations within the CFTR gene. The frequency
      distribution of polymorphic TUB9 marker alleles across the non-delta F508
      chromosomes in the three studied groups were estimated. Homozygotes for the TUB9
      allele 1 were shown to have identical GATT-TUB9-M470V haplotypes.

PMID- 9162704
TI  - [Distribution of alleles of microsatellite loci HUMCYAR04 and D19S253 in
      population samples of two Russian cities].
AB  - In population samples of Moscow and Tomsk, allelic polymorphism of microsatellite
      loci HUMCYAR04 and D19S253 was studied by polymerase chain reaction. Seven
      HUMCYAR04 alleles (181-205 bp) and nine alleles (208-240 bp) of the D19S253 locus
      were identified. In both population samples, the absence of statistically
      significant differences in the distribution of allele frequencies for these loci
      was demonstrated. The distribution of the observed genotype frequencies was shown
      to correspond to the Hardy-Weinberg equilibrium in both populations. Mendelian
      inheritance of these tandem repeats was demonstrated by an analysis of two large
      families. The parameters of polymorphism information content for the loci studied
      were determined; comparative analysis of allele frequencies with corresponding
      data for a number of populations was performed. These short tandem repeats were
      proposed for use in personal identification and paternity tests.

PMID- 9162705
TI  - [Highly polymorphic regions of the genes for apolipoprotein B and angiotensin
      converting enzyme in the Udmurt population].
AB  - The hypervariable regions of the 3'-end of the apolipoprotein B gene (APOB3'
      VNTR) and angiotensin converting enzyme gene (ACE), which had 10-15 alleles each,
      were studied in a sample from the Udmurt population by means of polymerase chain
      reaction (PCR). From the literature data, the genetic position of Udmurts among
      12 groups of Caucasoid, Mongoloid, and Negroid populations was determined. The
      data obtained by the method of principal components indicated that Udmurts held
      an isolated position in the northern branch of the Caucasoid race.

PMID- 9162706
TI  - [Chromosomal localization of M/SAR from DNA of the clone lambda20p1.4 in
      Drosophila melanogaster salivary glands].
AB  - M/SAR of Drosophila melanogaster DNA clone gamma 20p 1.4 was localized on
      chromosomes by in situ hybridization of the gamma 20p 1.4 DNA fragment and its
      deletion mutants with salivary gland chromosomes of third instar larvae of the
      lines Canton S and Oregon R. The M/SAR sequence, capable of specifically binding
      to lamin in vitro, was detected in the pericentric regions 20CD, 40EF, 41AB, the
      proximal part of region 81 of chromosome 3, and region 101 of chromosome 4, which
      attach to the nuclear envelope in cells of D. melanogaster salivary glands, and
      in region 49D, which does not come into contact with the nuclear periphery. This
      is the first M/SAR localized in pericentric chromatin of D. melanogaster.

PMID- 9162707
TI  - [Polymorphism of pericentromere heterochromatin of polytene chromosomes of
      ovarian trophocytes in natural populations of the malaria mosquito Anopheles
      messeae Fall].
AB  - Pericentric heterochromatin polymorphism in chromosome 2 of ovarian trophocytes
      was studied in three natural populations of the malaria mosquito Anopheles
      messeae Fall. It is shown that pericentric heterochromatin blocks occur in four
      different variants whose sizes are at the 1:2:3:4 ratio (single, double, triple,
      and quadruple blocks). Mosquitoes with homo- and heterozygous variants of these
      blocks were identified. By analyzing frequency distribution of different size
      variants, interpopulation differences in this parameter were revealed. Mosquitoes
      with double heterochromatin blocks prevailed in the southern population, whereas
      those with triple blocks were more abundant in the northern population.

PMID- 9162708
TI  - [Role of the rpoS gene in the regulation of expression of plasmid genes
      determining the synthesis of C51 microcin].
AB  - In cells mutant for the rpoS gene coding the sigma s subunit of RNA polymerase,
      synthesis of antibiotic microcin C51, which is produced by Escherichia coli, is
      absent or extremely reduced. In experiments with a cloned promoter of the
      microcin operon, the sigma s subunit was shown to participate in regulation of
      transcription of plasmid genes that determine microcin synthesis.

PMID- 9162710
TI  - [Snowboard sports technique, injury pattern, prevention].
AB  - Although, in Europe, snowboarding is a young sport, it has already established
      itself and, in common with Alpine skiing, is represented in the Olympics. Its
      biomechanical aspects (technique, shoeboard connection), lead not only to a
      typical pattern of movements, but also to a snowboard-specific pattern of
      injuries, which differs from that seen with Alpine skiing. In the case of
      snowboarding, the upper limbs are appreciably more often involved in injuries
      than are the lower extremities. The most common injuries are fractures of or
      close to the wrist. Since many children and adolescents are to be found among
      snowboarding fans, the percentage of epiphyseal injuries is high. Depending on
      the style employed-Alpine or freestyle-the risk of lower limb injuries differ in
      terms of ankles and knee injuries. Through the use of special protective
      equipment, such as gloves provided with extra protection for wrist and fingers,
      (possibly also helmets, knee and elbow protectors for beginners), together with
      improvements in technique in a snowboard school, and the optimisation of the
      materials used by the industry, the risk of injury can be reduced.

PMID- 9162709
TI  - [Sinusitis--the "normal nose" has medical advantages].

PMID- 9162711
TI  - [Conservative treatment of cruciate ligament rupture. Magnetic resonance
      tomography provides prognostic information for conservative healing].
AB  - Ruptures of the cruciate ligaments continue to pose both diagnostic and
      therapeutic problems. On the basis of structural analysis of MR images obtained
      after the accident and the results of conservative treatment, it can be shown
      that function healing of the rupture can result, when, for example, the synovial
      membrane (capsule) is preserved (70%). It proved possible to show and objectify
      this using MRI and measurements.

PMID- 9162712
TI  - [Interventions on the anterior cruciate ligament: consider the innervation!].

PMID- 9162713
TI  - [Severe injuries in winter sports are on the increase. Interview by Dr. rer. nat.
      Anita Schweiger].

PMID- 9162714
TI  - [Alternatives in therapy of arthroses].

PMID- 9162715
TI  - [The diabetic patient in general practice. Single diagnosis of hyperglycemia is
      not adequate].

PMID- 9162716
TI  - [Is eating sweets becoming easier now?].

PMID- 9162717
TI  - [Infections of the urogenital tract. 1: Quality assurance in diagnosis-
      principles and basic diagnosis].

PMID- 9162719
TI  - [Does lowering blood pressure also prevent stroke?. Interview by Dr. med. Monika
      Flasnoecker].

PMID- 9162718
TI  - [Parkinson disease--problems in long-term treatment. Dopamine agonists optimize L
      dopa therapy].
AB  - In a 59-year-old male with a 10 year history of Parkinson's disease, progressive
      movement disorders occurred under medical treatment (end-of-dose akinesia and
      peak-dose dyskinesia). Thereupon his treatment was changed to a combination of L
      dopa/ decarboxylase inhibitor administered during the day in 5 fractions, and
      additionally a slow-release dopa preparation given on retiring for the night. At
      the same time, the patient received the dopamine agonist lisuride. While the
      patient was hospitalized for surgery, his anti-parkinsonism regimen was initially
      stopped and then continued in changed form. In the following weeks he experienced
      a drastic impairment of mobility and, in particular, suffered pronounced
      nocturnal hypokinetic events. A second period of hospitalization became
      necessary, a complex medical therapeutic regimen similar to the previously
      successful combination was established. This resulted in satisfactory mobility,
      and the patient was able to go back to work.

PMID- 9162720
TI  - [General practice 2000--what should be done today?].

PMID- 9162721
TI  - [Does estrogen replacement prevent Alzheimer's disease?].

PMID- 9162722
TI  - [A leap into the cold water of general practice].

PMID- 9162723
TI  - [Drug therapy of benign prostatic hyperplasia concentrates on early stages].

PMID- 9162724
TI  - [Experimental investigations on the resorption of essential materials in rat
      kidneys].

PMID- 9162725
TI  - [Fibrocystic mastopathy and epithelial proliferation in female breasts
      histological sections].

PMID- 9162726
TI  - [Hydronephrosis as a results of kidney puncture. Experimental studies in the
      kidneys of healthy rabbits].

PMID- 9162728
TI  - [Frequency of confluens sinuum in man].

PMID- 9162727
TI  - [Fuchsinophilic (orceinophilic) intercellular interstitium of salivary gland
      mixed tumors].

PMID- 9162729
TI  - [Morphology of lymphatic obstruction dependent coronary changes].

PMID- 9162730
TI  - [Biomorphosis of the kidney boundary interstitium and intrarenal arteries].

PMID- 9162731
TI  - [Calciphylactic arteriopathy].

PMID- 9162732
TI  - [Questions of syntropy between carcinoma and arteriosclerosis in 2800
      histological cases].

PMID- 9162733
TI  - The essentials for managing student home healthcare experiences.
AB  - As hospitals downsize, nursing education programs are moving into the home care
      setting to provide clinical experience to students. This article provides home
      care agencies, nurses, and educational programs with strategies for the
      management of these experiences and discusses the benefits that can be
      experienced by all who participate.

PMID- 9162734
TI  - Eker rat model of a Mendelian dominantly inherited cancer.

PMID- 9162735
TI  - Molecular and cellular basis for cell to cell interaction: its significance in
      cancer. Proceedings of the 24th International Symposium of the Princess Takamatsu
      Cancer Research Fund. Tokyo, Japan.

PMID- 9162736
TI  - Aunt Minnie's corner. Chiari I malformation with associated hydrosyringomyelia.

PMID- 9162738
TI  - Numerical aberrations of chromosome 7 detected in 15 microns paraffin-embedded
      tissue sections of primary cutaneous melanomas by fluorescence in situ
      hybridization and confocal laser scanning microscopy.
AB  - Fluorescence in situ hybridization (FISH) to sections of formalin-fixed paraffin
      embedded archival tissues allows the detection of gene or chromosome copy number
      changes in interphase cell nuclei within the histological context and thus may be
      of particular interest in tumor pathology. In this report, we describe the
      application of FISH to thick (15 microns) paraffin sections of 7 primary
      cutaneous malignant melanomas. A chromosome 7-specific centromeric DNA probe was
      used to detect numerical aberrations of chromosome 7. By optical sectioning using
      confocal laser scanning microscopy (CLSM) only complete, uncut interphase cell
      nuclei were scored. The mean percentage (+/- SEM) of melanoma cell nuclei with
      three hybridization spots was (20.7 +/- 2.8)%; (6.8 +/- 1.0)% of nuclei showed
      one spot and (5.0 +/- 1.2)% four or more spots. The frequency distribution of
      spot numbers among melanoma cell nuclei and normal keratinocyte nuclei was
      significantly different (chi(2) = 176.8, df = 5, p < 0.001). Trisomy 7 was
      detected in all 7 cases analyzed, mostly associated with monosomy 7 or polysomy
      7. The approach used in our study and the data obtained could be useful for
      further studies designed to investigate a possible involvement of chromosome 7 in
      melanocytic tumor progression.

PMID- 9162737
TI  - Inverse correlation between CD34 expression and proline-4-hydroxylase
      immunoreactivity on spindle cells noted in hypertrophic scars and keloids.
AB  - The CD34 positive (CD34+) spindle cells constitute a special population of
      spindle cells which shows a unique distribution in the skin. So far, however, the
      functional role of CD34+ spindle cells and the regulation of CD34 expression on
      dermal spindle cells are totally unknown. We examined immunohistologically the
      pattern of the expression of CD34 and proline-4-hydroxylase, a marker for the
      fibroblasts that participate in active collagen synthesis, on dermal spindle
      cells at various stages of scar and keloidal tissues. Dermal spindle cells in the
      lesions of hypertrophic scar and those at inflammatory expanding borders of
      keloids totally lost CD34 expression, but they strongly expressed proline-4
      hydroxylase. On the other hand, they expressed CD34, together with decreased
      immunoreactivity to anti-proline-4-hydroxylase antibody, in non-inflammatory
      scars or in a non-inflammatory central portion of keloid. In two cases of scars,
      in which inflammation began to subside, double immunofluorescence demonstrated
      that both CD 34 and proline-4-hydroxylase were expressed on the same spindle
      cells. CD34 expression, once disappeared from the lesions of hypertrophic scar or
      keloid, seems to return on CD34-proline-4-hydroxylase+ cells, when the initial
      inflammatory changes begin to regress. There is a reverse correlation between
      CD34 expression on spindle cells and the synthesis of type I collagen in the
      skin.

PMID- 9162739
TI  - Ca(2+)-binding proteins S100A6 and S100B in primary cutaneous melanoma.
AB  - PURPOSE: Commercially available polyclonal antibodies against a mixture of bovine
      brain S100 proteins have become an established marker for immunohistochemical
      characterization of malignant melanoma. However, the commercially available
      antibodies used are undefined and to date, 13 different human S100 proteins are
      known. The purpose of this study was to examine the expression of 4 newly
      available polyclonal antibodies against the human recombinant Ca(2+)-binding S100
      proteins, S100A1, S100A2, S100A4 and S100A6, in cutaneous melanoma and to
      correlate these findings with the standard S100 staining as well as with the
      metastatic potential of the primary. METHODS: 39 formalin-fixed paraffin-embedded
      primary cutaneous melanomas were incubated with polyclonal antibodies against
      recombinant human S100 proteins using the APAAP method. The extent of staining
      was qualitatively assessed and a staining index was calculated. Findings were
      correlated to the metastatic potential and the overall survival in all patients.
      RESULTS: Staining with antibodies against human S100A6 as well as with antibodies
      against conventional bovine S100 proteins was positive in all specimens. No
      correlation was found between the extent of protein expression and patients'
      outcome for standard S100 staining as well as for S100A6. S100A1, S100A2 and
      S100A4 staining could not be used for statistical analysis due to their low
      expression in melanoma. CONCLUSION: Staining was positive using S100A6 antibodies
      in all specimens, the quality being inferior to the commercially available S100
      antibody. Highly specific and well characterized antibodies against the
      individual S100 proteins are now available for future immunohistochemical
      characterization studies in melanomas.

PMID- 9162740
TI  - The molecular pathology of lecithin:cholesterol acyltransferase (LCAT) deficiency
      syndromes.
AB  - Lecithin:cholesterol acyltransferase (LCAT) deficiency syndromes represent a
      group of rare genetic disorders of HDL metabolism that have been the subject of a
      large number of clinical, biochemical, and genetic studies. Of special interest
      are patients with LCAT-related disorders with severe HDL deficiency and the
      apparent absence of premature atherosclerosis. This finding is inconsistent with
      the general concept that low HDL cholesterol levels are an obligate risk factor
      for atherosclerosis. In this review, we describe 36 natural mutations in the LCAT
      gene that result in either familial LCAT deficiency (FLD) or the milder phenotype
      known as fish-eye disease (FED). We propose a new classification of the natural
      mutations of the LCAT gene that are described to date. The defects are divided
      into four classes based on both the clinical and biochemical characterization of
      the patient and data that were obtained from the functional assessment of the
      mutant proteins. We define FLD-associated mutations that underlie a complete or
      nearly complete loss of LCAT activity due to null mutations (Class 1), and
      missense mutations (Class 2), respectively. In addition, we distinguish two
      classes of FED-associated mutations (Classes 3, 4) that underlie a partial
      impairment of LCAT activity but differ in their lipoprotein substrate
      specificity. In addition, we review the evidence of atherosclerosis in subjects
      with LCAT deficiency syndromes. The observation that 6 (all males) of a total of
      19 FED subjects suffered from premature CAD (as defined by < 55 years of age and
      < 60 years of age for women and men, respectively) challenges the earlier
      assumption that the FED phenotype is not associated with increased risk of CAD.
      However, premature CAD remains an unusual clinical complication in FLD subjects.

PMID- 9162741
TI  - Inhibition of apolipoprotein B secretion by IL-6 is mediated by EGF or an EGF
      like molecule in CaCo-2 cells.
AB  - Small intestinal mucosal inflammation observed in celiac disease is associated
      with the local release of growth factors and various cytokines. In a previous
      study, we investigated the effect of various cytokines on triacylglycerol and
      apoB secretion by CaCo-2 cells and observed that TNF-alpha, IL-1 beta, and
      particularly IL-6, decreased apolipoprotein (apo) B and triacylglycerol
      secretion. In this study, we explored possible mechanisms to explain the
      inhibitory effect of IL-6 on apoB secretion. IL-6, 10 ng/mL, added to the
      basolateral medium of CaCo-2 cells grown on semi-permeable filters, decreased
      apoB secretion by 42%. Adding a blocking monoclonal antibody (mAb 528) to the EGF
      receptor completely prevented this effect. IL-6 decreased the amount of EGF
      receptor protein and the binding of iodinated EGF to its receptor by 50% and 30%,
      respectively. Incubation of cells with various ligands to the EGF receptor, such
      as EGF, TGF-alpha, HB-EGF, and amphiregulin, also decreased apoB secretion.
      Inhibition of apoB secretion by EGF was prevented by the mAb 528 or an EGF
      neutralizing antibody. In a dose-dependent manner, the neutralizing antibody to
      EGF prevented the decrease in secretion of apoB, triacylglycerol mass, and cell
      surface binding of labeled EGF caused by IL-6. Similar to the effects of IL-6,
      EGF decreased the secretion of triacylglycerol mass and the synthesis and
      secretion on newly synthesized apoB. The results suggest that, in CaCo-2 cells,
      IL-6 causes the release of EGF or an EGF-like molecule. By binding to cell
      surface EGF receptors, the molecule then causes a decrease in triacylglycerol and
      apoB secretion.

PMID- 9162742
TI  - Investigation of plasma membrane-associated apolipoprotein E in primary
      macrophages.
AB  - Our previous studies identified the lysosome as the compartment for degradation
      of newly synthesized apoE in primary macrophages. Lysosomal degradation of newly
      synthesized apoE is extensive and rapid (> 50% in 60 min). In the present study
      we tested the hypothesis that the macrophage cell surface is part of the
      itinerary of apoE in its path to the lysosomes. We therefore examined the
      existence and size of the apoE pool associated with the macrophage cell surface.
      Such a pool may not only provide a mechanism of targeting apoE for lysosomal
      degradation, by endocytosis, but also have important implications for the
      metabolism of lipoproteins by macrophages. Treatment of macrophages with heparin
      (10 micrograms/ml and 5 mg/ml) and heparinase I (1 U/ml), which releases
      substantial amounts of apoE from HepG2 cells, results in no additional release of
      apoE from macrophages. Treatment of macrophages with xyloside (1 mM) or GRGDTP
      (500 micrograms/ml) does not decrease the extent of cell-associated apoE. Both
      immunogold labeling, followed by electron microscopy, and immunofluorescent
      labeling and light microscopy further confirm the lack of significant amounts of
      cell surface-associated apoE in macrophages. In contrast, immunolabeled apoE is
      readily observed in permeabilized cells. Taken together, these data indicate the
      absence of significant apoE-glycosaminoglycan interaction at the macrophage cell
      surface. The lack of such an interaction is likely due to paucity of heparan
      sulfate proteoglycans on the macrophage cell surface, when compared to
      hepatocytes. Along with our previous observations. (Deng. J., V. Rudick, and L.
      Dory, 1995. J. Lipid Res. 36:2129-2140), these results suggest direct targeting
      of a portion of newly synthesized apoE from trans-Golgi network to lysosomes for
      degradation, without involving the plasma membrane and endocytosis.

PMID- 9162743
TI  - Fasting-induced selective mobilization of brown adipose tissue fatty acids.
AB  - This study was conducted to determine whether there is selective mobilization of
      fatty acids from brown adipose tissue. Rats were fed a fish-oil diet and then
      fasted for 0, 7, or 10 days followed by analysis of the fatty acid content and
      composition of triacylglycerols (TAG) and phospholipid (PL) in interscapular
      brown adipose tissue (IBAT). Fatty acids were selectively lost from IBAT
      triacylglycerols, the mobilization following the same structural rules as those
      previously demonstrated for white adipose tissue. Fractional mobilization
      increased with unsaturation at a given chain length and tended to decrease with
      chain length at a given unsaturation. However, linoleic acid (18:2 n-6) was
      mobilized significantly less than predicted by these structural rules. In IBAT
      phospholipid, fatty acids were also selectively lost but there was no such
      relationship between the fractional mobilization of a fatty acid and its
      structure. The fatty acids of the n-6 series were exceptional in their behavior
      because they displayed below average fractional mobilization. In fact, linoleic
      and arachidonic acids actually increased their mass in IBAT phospholipid during
      the fast. It is concluded that, in IBAT, fatty acids are selectively mobilized
      during a fast, and that fasting-induced remodeling of the fatty acid composition
      leads to the selective retention of linoleate in the case of TAG and all the n-6
      fatty acids in the case of PL.

PMID- 9162744
TI  - Implications of endogenous and exogenous lipoprotein lipase for the selective
      uptake of HDL3-associated cholesteryl esters by mouse peritoneal macrophages.
AB  - To investigate the implications of endogenous LPL on selective uptake of HDL3
      associated cholesteryl esters (HDL3-CEs) by mouse peritoneal macrophages (MPMs),
      we have performed uptake experiments with MPMs obtained from control mice and
      transgenic knockout animals expressing LPL exclusively in muscle but not in
      macrophages. The capacity for HDL3 holoparticle, total HDL3-CE, and selective
      HDL3-CEs was independent of the expression of functional endogenous LPL (161 vs.
      187, 1251 vs. 1300, and 1900 vs. 1113 ng HDL3/mg cell protein; control and LPL
      deficient macrophages, respectively). Both control and LPL-deficient macrophages
      displayed, however, pronounced capacity for total HDL3-CE uptake in excess of
      HDL3 holoparticle uptake exceeding particle uptake by 7-fold. Despite the fact
      that endogenous LPL was without any effect on selective uptake, the addition of
      exogenous LPL led to a significant increase in cellular selective HDL3-CE uptake.
      Upon addition of purified LPL, HDL3 holoparticle (internalization and
      degradation), total HDL3-CE, and selective HDL3-CEs, was increased up to 2-fold.
      HDL3 holoparticle binding to control and LPL-deficient MPMs at 4 degrees C was
      enhanced 2.7- and 2.6-fold, respectively, in the presence of LPL. The present
      results suggest that endogenous LPL is without effect on selective uptake of HDL3
      CEs. In contrast, the addition of exogenous LPL enhanced selective uptake of HDL3
      CEs along with HDL3 holoparticle uptake apparently by the proposed bridging
      function of the enzyme.

PMID- 9162745
TI  - Developmental down-regulation of receptor-mediated endocytosis of an insect
      lipoprotein.
AB  - Fat body cells of insects exhibit a high-affinity lipoprotein binding site at
      their cell surfaces. In the present study, the lipoprotein binding site was
      identified as an endocytotic receptor involved in receptor-mediated uptake of its
      lipoprotein ligand, high density lipophorin. After an initial period of high
      endocytotic uptake of high density lipophorin in the adult stage, this process
      strongly diminished. In the same period, a dramatic increase in cell surface
      associated lipoproteins was observed. When animals were starved, however,
      internalization of lipoproteins was maintained. The pathway followed by the
      internalized lipoproteins appears to be different from the endosomal/lysosomal
      pathway, as the vast majority of apolipoproteins seemed to escape from lysosomal
      hydrolysis. In addition, no substantial intracellular accumulation of
      apolipoproteins was observed, suggesting that internalized lipoproteins were
      resecreted. It is unlikely that internalization is required for transport of the
      two major lipid components of insect lipoproteins, diacylglycerol and
      cholesterol, as inhibition of endocytosis neither affected the exchange of these
      lipids between lipoproteins and fat body cells nor influenced the loading of
      diacylglycerol onto lipoproteins in response to adipokinetic hormone. We
      postulate that the endosomal environment may facilitate transport of components
      which, unlike diacylglycerol and cholesterol, cannot be transported by simple
      aqueous diffusion.

PMID- 9162746
TI  - Long-chain polyunsaturated fatty acids in the sn-2 position of
      phosphatidylcholine decrease the stability of recombinant high density
      lipoprotein apolipoprotein A-I and the activation energy of the
      lecithin:cholesterol acyltransferase reaction.
AB  - The lecithin:cholesterol acyltransferase (LCAT) kinetics and activation energy
      and the stability of apolipoprotein A-I (apoA-I) were investigated using
      recombinant HDL (rHDL) containing phosphatidylcholine (PC), [3H]cholesterol, and
      apo A-I. The PC component of the rHDL contained sn-1 16:0 and sn-2 18:1 (POPC),
      20:4 (PAPC), 20:5 n-3 (PEPC), or 22:6 n-3 (PDPC) or 10% of the respective PC
      species and 90% sn-1 18:1, sn-2 16:0 PC ether (OPPC ether). The appVmax of the
      rHDL containing 100% PC varied 10-fold and was ordered POPC > PEPC > PAPC > PDPC,
      whereas the appKm values varied 19-43 microns PC. The ether-containing rHDL had
      appVmax values 17-40% of their respective 100% PC rHDL, but maintained the same
      rank order. The activation energy of LCAT was lower for rHDL containing long
      chain polyunsaturated fatty acids (PUFA) compared to rHDL containing 100% POPC or
      10% PC/90% OPPC ether. The concentration of guanidine HCl (D1/2) required to
      denature one-half of the apoA-I on rHDL containing long chain PUFA was reduced
      (1.2-16 M) compared to those containing 100% POPC or 10% PC/90% OPPC (2.2-2.4 M)
      and there was a strong correlation (r = 0.71) between LCAT activation energy and
      the stability of apoA-I (i.e., D1/2). We conclude that long chain PUFA in the sn
      2 position of PC decreases the catalytic efficiency of LCAT, the activation
      energy of the LCAT reaction and the stability of apoA-I on the rHDL particles.
      The strong association between rHDL apoA-I stability and LCAT activation energy
      suggests that the temperature-dependent step of the LCAT reaction may be
      sensitive to the strength of the interaction of apoA-I with rHDL PC.

PMID- 9162747
TI  - High polyunsaturated fatty acid, thromboxane A2, and alpha-fetoprotein
      concentrations at the human feto-maternal interface.
AB  - Polyunsaturated fatty acids (PUFA) like arachidonic (C20:4) and docosahexaenoic
      (C22:6) acids are essential for harmonious fetal development. This study
      evaluates, at near term, the distributions of free fatty acids (FFA) and their
      fetal carrier protein, alpha-fetoprotein (AFP) in the maternal (M) and fetal
      circulation (umbilical arteries (A) and vein (V)), focusing on the feto-material
      interface where maternal intervillous blood (I) contacts the fetal trophoblast.
      FFA concentrations in intervillous and maternal blood were similar, while those
      in umbilical arteries and vein were 2- to 4-fold lower (P < 0.001). There were
      more saturated FFA in umbilical vein (41%) and arteries (44%) blood than in
      maternal (30%) and intervillous (32%) blood (P < 0.001). Monounsaturated FFA
      predominated (P < 0.001) in maternal (43%) blood, but not in intervillous (35%),
      umbilical vein (33%) and arteries (31%) blood. Di-triunsaturated FFA were similar
      in intervillous and maternal (25%) blood and lower in umbilical vein and arteries
      (16%) (P < 0.001). PUFA were low in maternal (2.5%) blood and higher in
      intervillous and umbilical vein and arteries (9%, P < 0.001); consequently, C20:4
      (40 microM) and C22:6 (16 microM) were the most abundant in the intervillous
      space. The AFP concentrations and AFP lectin-reactive isoforms were similar in
      intervillous and umbilical vein and arteries blood, but immuno-electrophoresis
      revealed a particular AFP conformation (less immuno-reactive, more anionic) in
      the intervillous space, suggesting that AFP is heavily loaded with PUFA at the
      feto-maternal interface. Prostacyclin derived from C20:4 was similar in all
      compartments but the thromboxane A2 concentration was 10-fold higher in
      intervillous blood than in maternal and umbilical vein and arteries blood. Thus
      the feto-maternal interface has a specific pattern of cell signalling molecules
      that might critically influence parturition.

PMID- 9162749
TI  - Incorporation of [U-14C]palmitate into rat brain: effect of an inhibitor of beta
      oxidation.
AB  - We examined the effect of a clinically therapeutic dose of methyl 2
      tetradecylglycidate (McN-3716, methyl palmoxirate, MEP) (2.5 mg/kg), an inhibitor
      of beta-oxidation of fatty acids, on incorporation of radiolabeled palmitic acid
      ([U-14C]PAM) from plasma into brain lipids of awake rats. Four hour pretreatment
      with 2.5 mg/kg MEP significantly increased the incorporation of [U-14C]PAM into
      brain lipids and substantially decreased aqueous radiolabeled metabolites in
      brain that can constitute unwanted background signal when analyzed by
      quantitative autoradiography. MEP treatment increased the lipid to aqueous
      background radioactivity from 0.8 to 3.0. Net rate of incorporation, k*, was
      significantly increased (60%) by MEP and was attributed to incorporation of [U
      14C]PAM into phospholipid and triglyceride brain compartments. MEP treatment did
      not affect the size of the fatty acyl-CoA pool or the distribution of the various
      molecular acyl-CoA species. These results indicate that MEP, at a dose of 2.5
      mg/kg (per os), can be used to increase incorporation of [1-(11C)]PAM for
      studying brain lipid metabolism in humans by positron emission tomography (PET).

PMID- 9162748
TI  - Effect of cholesterol on apolipoprotein A-I binding to lipid bilayers and
      emulsions.
AB  - The effects of cholesterol (Chol) on the interaction of apolipoprotein A-I (apoA
      I) with phospholipid bilayer vesicles and lipid emulsions were investigated. ApoA
      I bound to phosphatidylcholine (PC) vesicles with higher affinity and lower
      capacity compared to triglyceride-PC emulsions. An increase in surface Chol in
      triglyceride-PC emulsions decreased the binding capacity without changing the
      binding affinity. In contrast, addition of Chol to PC vesicles caused a marked
      increase in capacity and decrease in affinity for apoA-I binding. ApoA-I caused a
      large release of entrapped aqueous dye, calcein, from PC vesicles, whereas this
      apoA-I-induced leakage was relatively small in the vesicles containing Chol. The
      incorporation of phosphatidylethanolamine into the vesicles also exerted effects
      similar to those of Chol on apoA-I binding and calcein leakage. The shifts of
      fluorescence emission maximum of dansyl lysine, probing the surface region of
      membranes, indicated that Chol as well as phosphatidylethanolamine increased the
      headgroup space of the vesicles. The binding maximum of apoA-I was closely
      correlated with the emission maximum of dansyl lysine, not with the fluorescence
      anisotropy of I-[4-(trimethylamino)phenyl]phenylhexatriene, suggesting that the
      binding capacity of apoA-I to the bilayer surface was modulated by the headgroup
      space rather than the acyl chain fluidity. These results show that Chol affects
      the bilayer surface so as to allow more apoA-I to bind to bilayers and may
      suggest the possibility of the interaction of apoA-I with Chol-enriched membrane
      domains.

PMID- 9162750
TI  - Alterations of VLDL composition during alimentary lipemia.
AB  - Apoliprotein (apo) B-100-containing very low density lipoprotein (VLDL) particles
      secreted from the liver accumulate in plasma during alimentary lipemia. To
      determine whether changes of VLDL composition occur in the postprandial state
      that may render these lipoproteins more atherogenic, apoE, C-I, C-II, and C-III,
      and lipids (triglycerides, phospholipids, and cholesterol) were measured in
      Svedberg flotation (Sf) 60-400 (large) and Sf 20-60 (small) VLDL before and after
      an oral fat load. Ten normotriglyceridemic (NTG) and three hypertriglyceridemic
      (HTG) healthy men were given a fat-rich mixed meal (1,000 kCal with 60.2 E% from
      fat). Triglyceride-rich lipoproteins were isolated by density gradient
      ultracentrifugation from plasma samples obtained before (fasting) and at 2-h
      intervals after the meal. VLDL was then separated from chylomicrons and their
      remnants by immunoaffinity chromatography using monoclonal antibodies 4G3 and
      5E11, recognizing apoB-100, but not apoB-48 epitopes. Large and small VLDL
      isolated from the NTG group were enriched with apoE and C-I, and cholesterol, but
      depleted of apoC-II in the postprandial state, whereas the apoC-III,
      triglyceride, and phospholipid contents were essentially unchanged. The
      compositional changes of VLDL in HTG subjects were similar but more pronounced
      compared with NTG subjects. We conclude that postprandial lipemia in healthy men
      induces transient compositional alterations of VLDL that link these lipoprotein
      species to the formation of atherosclerosis.

PMID- 9162751
TI  - Dietary fats modulate the regulatory potential of dietary cholesterol on
      cholesterol 7 alpha-hydroxylase gene expression.
AB  - Cholesterol 7 alpha-hydroxylase (cyp7) is the rate-limiting enzyme in bile acid
      biosynthesis. Previously, dietary cholesterol was shown to induce cyp7 gene
      expression. However, recent studies have produced data that are inconsistent with
      this observation, suggesting the possibility that other factors in the diet are
      also important in the regulation of cyp7 by dietary cholesterol. The effect of
      dietary fats on the ability of dietary cholesterol to regulate cyp7 activity and
      mRNA abundance was assessed. High fat diets composed primarily of polyunsaturated
      (PUFA), monounsaturated (MUFA), or saturated (SFA) fatty acids induced
      hypercholesterolemia regardless of whether cholesterol was present or not.
      However, the effects of each diet on bile composition and hepatic cholesterol
      content were variable. Microsomal fatty acid profiles reflected the fatty acid
      composition of the diets. Addition of cholesterol to the PUFA diet increased cyp7
      mRNA abundance and activity, analogous with the results observed in mice fed a
      chow plus cholesterol diet. On the other hand, addition of cholesterol to diets
      high in MUFA or SFA caused a significant reduction of cyp7 mRNA abundance and
      activity. Addition of cholesterol to all the diets caused the expected changes in
      low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A
      reductase mRNA abundance but was not correlated with the changes in cyp7 mRNA
      abundance. The relationship between cyp7 mRNA abundance and hepatic total
      cholesterol content or hepatic microsomal cholesterol content was evident,
      suggesting that cholesterol status does not necessarily determine cyp7 mRNA
      abundance. The results of this study illustrate that the type of dietary fat is
      important in elaborating the regulatory potential of dietary cholesterol on cyp7
      gene expression and suggest that the regulation of cyp7 gene expression does not
      involve the classical sterol-mediated pathway.

PMID- 9162752
TI  - Amino terminus of apolipoprotein B suffices to produce recognition of
      malondialdehyde-modified low density lipoprotein by the scavenger receptor of
      human monocyte-macrophages.
AB  - Malondialdehyde, a product of lipid peroxidation, produces threshold conversion
      of low density lipoprotein (LDL) to a form recognized by type I and type II
      scavenger receptors of monocyte-macrophages. To investigate whether localized
      domains of human apoB-100 protein provide recognition determinants, we tested the
      ability of several different apoB-bearing particles to interact with the
      scavenger receptor of human monocyte-macrophages. Genetically engineered,
      carboxyl-terminally truncated apoB proteins assembled into lipoprotein form were
      labeled by fluorescent dye. Fluorescence microscopy and quantitative fluorescent
      spectrophotometry showed that purified particles containing as little as 23% of
      the apoB amino-terminus were internalized by the scavenger receptor after, but
      not before, malondialdehyde modification. There was no recognition of the
      particles by the LDL receptor. Similar results were obtained with human plasma
      LDL homozygous for carboxyl-terminally truncated apoB-45.2. Liposome-incorporated
      fusion protein containing apoB residues 547-735 displayed specific uptake by the
      scavenger receptor without modification by malondialdehyde. In contrast, fusion
      proteins containing apoB residues 3,029-3,133 or a short amino terminal segment
      failed to interact. Thus, primary sequence presented by residues 1-1,084 sufficed
      to produce recognition of modified LDL by the scavenger receptor. These receptor
      combining domains were sequestered when secreted in lipoprotein form and were
      expressed upon malondialdehyde modification. When packaged exogenously in
      liposome form, fusion protein containing apoB residues 547-735, containing
      approximately 4% of the primary sequence, mediated scavenger receptor-dependent
      uptake and hydrolysis. Our findings provide an additional function or the amino
      terminal region of apoB and demonstrate that primary sequence presented by the
      first 2% of apoB-100 protein suffices to produce recognition on malondialdehyde
      modified LDL by the scavenger receptor of human monocyte-macrophages.

PMID- 9162753
TI  - Chemical shift imaging at 4.7 tesla of brown adipose tissue.
AB  - In vivo distinction between small deposits of brown adipose tissue (BAT) and
      surrounding tissues may be difficult. In this article, we propose an experiment
      paradigm, based on techniques of chemical shift magnetic resonance imaging (CSI),
      which can improve the methods presently available for the study of BAT. Male rats
      were examined in an imager-spectrometer equipped with a 4.7 T magnet. Proton
      spectra of isolated BAT deposits showed that both fat and water protons
      contributed significantly to the genesis of the magnetic resonance signal. An
      equivocal definition of BAT deposits was obtained by three (respectively, spin
      echo, water-selective, and fat-selective) images. The spin-echo (SE), T1-weighted
      image provided the best anatomical description of the structures. The images
      selective for fat-protons displayed the degree of lipid accumulation in each
      area. The images selective for water-protons provided an internal control of
      adipose tissue localization. The proposed paradigm allows an unequivocal
      definition of BAT deposits and appears particularly useful in studies where
      experimental manipulation (i.e., cold acclimation or drug treatment) produces
      changes in this issue.

PMID- 9162754
TI  - Effect of micellar beta-sitosterol on cholesterol metabolism in CaCo-2 cells.
AB  - CaCo-2 cells were used to address the effect of the plant sterol, beta
      sitosterol, on cholesterol trafficking, cholesterol metabolism, and apoB
      secretion. Compared to cells incubated with micelles (5 mM taurocholate and 250
      microM oleic acid) containing cholesterol, which caused an increase in the influx
      of plasma membrane cholesterol to the endoplasmic reticulum and increased the
      secretion of cholesteryl esters derived from the plasma membrane, beta-sitosterol
      did not alter cholesterol trafficking or cholesteryl ester secretion. Including
      beta-sitosterol in the micelle together with cholesterol attenuated the influx of
      plasma membrane cholesterol and prevented the secretion of cholesteryl esters
      derived from the plasma membrane. Stigmasterol and campesterol had effects
      similar to beta-sitosterol, although campesterol did not promote a modest influx
      of plasma membrane cholesterol. Including beta-sitosterol in the micelle with
      cholesterol decreased the uptake of cholesterol. Compared to cholesterol, 60%
      less beta-sitosterol was taken up by CaCo-2 cells. No observable esterification
      of beta-sitosterol was appreciated and the transport of the plant sterol to the
      basolateral medium was negligible. Cholesterol synthesis and HMG-CoA reductase
      activities were decreased in cells incubated with beta-sitosterol. This was
      associated with a decrease in reductase mass and mRNA levels. Cholesteryl ester
      synthesis and ACAT activities were unaltered by beta-sitosterol. Both
      stigmasterol and campesterol decreased reductase activity, but only campesterol
      increased ACAT activity. beta-sitosterol did not affect the secretion of apoB
      mass. The results suggest that beta-sitosterol does not promote cholesterol
      trafficking from the plasma membrane to the endoplasmic reticulum. beta
      sitosterol interferes with the uptake of micellar cholesterol causing less plasma
      membrane cholesterol to influx and less cholesteryl ester to be secreted. Despite
      its lack of effect on cholesterol trafficking, beta-sitosterol decreases
      cholesterol synthesis at the level of HMG-CoA reductase gene expression.

PMID- 9162755
TI  - Molecular association of normal alkanoic acids with their thallium(I) salts: a
      new homologous series of fatty acid metal soaps.
AB  - A new homologous series of thallium(I) hydrogen dialkanoates, fatty acid thallium
      soaps, from the dipropane up to the ditetradecane is reported for the first time.
      This association with 1:1 stoichiometry is the only one exhibited by the thallium
      derivatives. They have been prepared by solidification of molten mixtures with
      equimolar proportions of acid and corresponding neutral salt, through
      crystallization from an anhydrous ethanolic solution of the mixture has also been
      successful in getting pure compounds with largest chain lengths. Vibrational
      spectroscopies clearly characterize these crystalline compounds as very strong
      hydrogen bonding systems. Assignations of active modes in proton and carbon
      nuclear magnetic resonance spectrometry (NMR) (in ethanol) and infrared (IR) and
      Raman spectra (in solid state) are reported. According to X-ray diffraction (XRD)
      they have monomolecular lamellar structures with the acyl chains arranged up and
      down to the cation/H-bond network in a methyl-to-methyl fashion, and vertically
      oriented to the basal plane. The acyl chains present all-trans conformation and
      alternating configuration (perpendicular orthorhombic subcell), like the beta'
      phases of other kinds of lipids. Lamellar thickness is reported for the six room
      temperature crystalline members. The molecular compounds present polymorphism,
      one crystal/crystal transition at temperatures close to the peritectical melting.
      Phase transition thermodynamics are also given and discussed with respect to
      their acid and salt parents. Their incongruent melting involves nearly 90% of the
      total enthalpic increments of both constituents' melting processes, making these
      compounds potential thermal energy storage materials.

PMID- 9162756
TI  - Ro 48-8.071, a new 2,3-oxidosqualene:lanosterol cyclase inhibitor lowering plasma
      cholesterol in hamsters, squirrel monkeys, and minipigs: comparison to
      simvastatin.
AB  - 2,3-Oxidosqualene:lanosterol cyclase (OSC, E.C. 5.4.99.7) represents a unique
      target for a cholesterol lowering drug. Partial inhibition of OSC should reduce
      synthesis of lanosterol and subsequent sterols, and also stimulate the production
      of epoxysterols that repress HMG-CoA reductase expression, generating a
      synergistic, self-limited negative regulatory loop. Hence, the pharmacological
      properties of Ro 48-8.071, a new OSC inhibitor, were compared to that of an HMG
      CoA reductase inhibitor, simvastatin. Ro 48-8.071 blocked human liver OSC and
      cholesterol synthesis in HepG2 cells in the nanomolar range; in cells it
      triggered the production of monooxidosqualene, dioxidosqualene, and
      epoxycholesterol. It was safe in hamsters, squirrel monkeys and Gottingen
      minipigs at pharmacologically active doses, lowering LDL approximately 60% in
      hamsters, and at least 30% in the two other species, being at least as
      efficacious as safe doses of simvastatin. The latter was hepatotoxic in hamsters
      at doses > 30 mumol/kg/day limiting its window of efficacy. Hepatic
      monooxidosqualene increased dose-dependently after treatment with Ro 48-8.071, up
      to approximately 20 micrograms/g wet liver or less than 1% of hepatic
      cholesterol, and it was inversely correlated with LDL levels. Ro 48-8.071 did not
      reduce coenzyme Q10 levels in liver and heart of hamsters, and importantly did
      not trigger an overexpression of hepatic HMG-CoA reductase, squalene synthase,
      and OSC itself. In strong contrast, simvastatin stimulated these enzymes
      dramatically, and reduced coenzyme Q10 levels in liver and heart. Altogether
      these findings clearly differentiate the OSC inhibitor Ro 48-8.071 from
      simvastatin, and support the view that OSC is a distinct key component in the
      regulation of the cholesterol synthesis pathway.

PMID- 9162757
TI  - Leukocyte low density lipoprotein receptor (LDL-R) does not contribute to LDL
      clearance in vivo: bone marrow transplantation studies in the mouse.
AB  - The targeted disruption of the low density lipoprotein (LDL) receptor gene in
      mice results in accumulation of plasma LDL cholesterol and in predisposition to
      diet-induced aortic atherosclerosis. Although the liver is the central organ for
      receptor mediated clearance of LDL, the in vivo role of other organs and tissues
      in LDL catabolism has not been directly studied. Since bone marrow-derived cells
      such as blood leukocytes and tissue macrophages express LDL receptors and
      contribute a large mass to the body, we designed bone marrow transplantation
      (BMT) experiments to reconstitute LDL receptor null mice [LDL-R(-/-)] with marrow
      obtained from LDL-R wild-type mice [LDL-R(+/+)] and evaluate the effects on
      parameters of plasma lipid metabolism. Although reconstitution of the
      transplanted mice with donor bone marrow cells was complete, no differences in
      plasma lipid levels and lipoprotein distribution were found between groups,
      irrespective of the diet used, and turnover studies using 125I-labeled LDL showed
      that LDL receptor expression by leukocytes and macrophages does not significantly
      contribute to plasma LDL clearance. The complementary experiment of transplanting
      LDL-R(-/-) marrow into C57BL/6 recipients [LDL-R(-/-)-->LDL(+/+)], performed to
      evaluate the role of leukocyte LDL-R in normocholesterolemic condition, also
      produced no effects on plasma lipid parameters. LDL binding studies using
      macrophages isolated from transplanted mice showed a lack of LDL-R expression.
      Thus, despite their large number and wide distribution, bone marrow-derived cells
      do not significantly influence receptor-mediated clearance of plasma LDL.

PMID- 9162759
TI  - Separation and quantification of apolipoprotein B-48 and other apolipoproteins by
      dynamic sieving capillary electrophoresis.
AB  - Apolipoprotein-B-48 is a structural protein exclusively associated with post
      prandial lipoproteins (chylomicrons). Apolipoprotein B-48 would be a useful
      marker to monitor the kinetics of chylomicrons in vivo, however, its quantitation
      is limited because of a low concentration in plasma and lack of specific
      antibodies. Dynamic sieving capillary electrophoresis (DSCE) has recently become
      widely available for the separation of nanomolar quantities of proteins by size
      and electrophoretic mobility. Here we describe the potential of DSCE to
      accurately quantitate apolipoprotein mass in one ml of plasma. Separation of
      human serum apolipoproteins was achieved through an uncoated fused silica glass
      capillary column with quantitation based on area response at 220 nm. The
      retention times of human apolipoprotein B-48, apolipoprotein B-100 and albumin
      were 8.96 min +/- 0.57%, 10.21 min +/- 0.72%, and 6.56 min +/- 0.4%, respectively
      (phase-standardized to internal reference). A significant correlation (r = 0.99)
      was observed between apolipoprotein concentrations and peak area response for
      mass ranges of 30-40 micrograms/ml. DSCE provides an alternative method for
      quantifying apolipoprotein B-48 and therefore, may be useful for studying
      postprandial lipoprotein metabolism.

PMID- 9162758
TI  - An improved method for quantification of cholesterol and cholesteryl esters in
      human monocyte-derived macrophages by high performance liquid chromatography with
      identification of unassigned cholesteryl ester species by means of secondary ion
      mass spectrometry.
AB  - The measurement of cholesteryl esters in human monocyte-derived macrophages using
      previously described high performance liquid chromatography methods is hampered
      by the presence in these cells of large amounts of triglycerides. We present a
      simple reversed phase high performance liquid chromatography protocol for
      quantification of cholesterol and cholesteryl esters in human
      monocyte/macrophages or other triglyceride-rich cells. Our method requires only
      lipid extraction and hydrolysis of triglycerides using a solution of ethanolic
      potassium hydroxide and is of sufficient sensitivity to allow measurement in
      10(5) cells. Use of this protocol led to the isolation of eight previously
      unassigned cholesteryl ester peaks comprising 16% of the total cholesteryl ester
      content of human monocyte-derived macrophages. Using time-of-light secondary ion
      mass spectrometry and synthesized authentic standards, seven of these peaks were
      found to comprise cholesterol esterified with polyunsaturated n-3 (omega 3)
      (cholesteryl eicosapentaenoate, docosatrienoate, docosapentaenoate, and
      docosahexaenoate) and n-6 (omega 6) (cholesteryl docosatetraenoate,
      eicosadienoate, and eicosatrienoate) fatty acids. The remaining peak was shown to
      be the cholesteryl ester of n-7 (omega 7) palmitoleic acid by comparison with a
      commercially available standard. The identification of all the cholesteryl esters
      in cholesterol-loaded human monocyte-derived macrophages will assist future
      studies of lipid metabolism in these cells.

PMID- 9162761
TI  - [Should a doctor be insistence in proposing surgery for cancer?].
AB  - On a basis of a large personal experience in treatment of patients with gastro
      intestinal cancer the author considers the expediency of convincing patients in
      surgical treatment of gastro-intestinal cancer, especially in the new social
      situation in Russia. Positive experience in long-term follow-up (more than 10-20
      years) of patients, operated on because of cancer, is one of pro factors for such
      a convincing. The results of long-term follow-up (exceeding 9 and 25 years) of
      the patients operated on in gastro-intestinal cancer (including primary-multiple
      cancer); the clinical case of a patient, who was operated for several times at
      the period of 13 years-10 malignant tumors were removed from his body; the
      clinical case of a patient, who was operated in case of 3 sinchronous cancers
      (cancers of pancteatic head, rectum and ascending colon) illustrate the benefit
      of the operative intervention.

PMID- 9162760
TI  - Remedial action program: a systematic approach to correcting performance
      problems.

PMID- 9162762
TI  - [Surgical classification of liver local lesions].
AB  - There is a variety of liver focal lesions (LFL) and every clinical case should be
      considered carefully in deciding the problem of indications to surgical
      treatment. The existing classifications, including the TNM classification, are
      limited by the peculiar features of liver anatomy. The authors propose an
      original surgical classification of LFL that combines TNM principles and
      segmental characteristics of volume of lesion. The classification takes into
      account intraorganic and extraorganic location of LFL, and marks it by special
      letter indices. The indication of nosology of LFL in combination with letter and
      a B digital indices provides the universality of classification. The authors
      recommend to use the classification in evaluation of malignant and benign liver
      lesions, as well as alveococcosis and liver trauma.

PMID- 9162763
TI  - [Diagnosis and surgical policy in benign lesions of liver].
AB  - The results of the treatment of 430 patients with benign tumors of the liver
      (BTL), including hemangiomas (41), nonparasitic solitary cysts (49), polycystosis
      (65) and parasitic hepatic lesions (alveococcosis-91, echinococcosis-184). To
      determine the character of a volume structure the accuracy of ultrasound and
      duplex sonography was tested (87.1-91.7%), as well as the accuracy of computer
      tomography (91.4-96.8%), angiography (90.6-96.3%), serological and
      radioimmunoassays. The use of these methods has increased the accuracy of
      diagnosis 2.2 times (in hemangiomas), nonparasitic cysts-to 1.2 times. The
      proposed methods of differential diagnosis and choosing of a proper treatment
      policy in patients with BTL made it possible to formulate indications and
      contraindications for the surgery, work out an optimal treating policy, depending
      on a character, location of BTL. The improvement of the surgical technique has
      decreased the rate of morbidity and mortality (2.5 and 1.5 times respectively).

PMID- 9162764
TI  - [Liver injuries].
AB  - The analyses of literature data on the results of the treatment of patients with
      mechanical injuries of the liver have been done. Analyses of 458 cases of open
      and closed liver traumas made it possible to determine 2 clinical forms of liver
      injuries: hemorrhagic and peritoneal. The separate subforms of traumatic liver
      disease in isolated multiple and combined injuries are determined. A diagnostic
      role of various methods was evaluated. Use of laparoscopy in 17 patients has
      exposed a superficial character of liver injuries and allowed not to perform
      surgery. Use of low-frequency ultrasound and polymeric adhesive sulfacrilat for
      the treatment of liver wounds in 63 patients has decreased the rate of
      postoperative complications to 18%, and the rate of mortality in mechanical liver
      injuries to 11.4% (in patients with mechanical liver injuries operated on with
      the use of ligature-free suture).

PMID- 9162765
TI  - [Diagnosis and surgical treatment of liver echinococcosis].
AB  - The results of surgical treatment of more than 600 patients with liver
      echinococcosis are analysed. The accuracy of ultrasound in diagnosis of the
      character of the damage is 88%; the combination of ultrasound methods with
      serology tests and computer tomography has increased the accuracy to 98-100%. New
      treatment approaches have been proposed depending on a character, location and
      extent of liver damage. The improvement of surgical technique made it possible to
      decrease the frequency of postoperative morbidity to 17.4% and mortality-to 3%.

PMID- 9162766
TI  - [Enteral detoxication in patients with liver cirrhosis and bleeding from the
      esophageal and gastric varices ].
AB  - A new method of enteral detoxication with the use of both well-known medicines
      ("Normase", "Sorbit") and new medicine-"Rafinosa" is described. Clinical
      effectiveness (normalization of neurological status) of these medicines
      correlates with normalization of blood amino acids unbalance, decrease of the
      catabolic processes and accumulation of toxic products of nitrogenous metabolism.
      All the above medicines (Italian made "Normase", "Sorbit" and Russian made
      "Rafinosa") are equally important for clinical practice. Enternal detoxication
      may be effective only in case of preventing relapsing bleeding by all possible
      measures from endoscopic thrombosing and endovascular embolisation of varicose
      veins to direct surgical operation on the esophageal and cardial veins.

PMID- 9162767
TI  - [The system of hemostasis in experimental liver transplantation].
AB  - The status of haemostatic factors in 28 pigs after orthotopic liver
      transplantation was evaluated. The major changes took place in fibrinolytic
      system during the "non-liver" stage: rapid increase of fibrinolytic activity,
      plasmin activity, plasmin activator activity. From the moment of blood supply
      restoration to a transplanted liver the tendency to normalisation of fibrinolysis
      was detected. The deficiency of plasma haemostatic factors and platelets has
      increased during all the follow-up period and should be corrected in time. The
      following principles of corrective therapy are formulated: inhibition of
      fibrinolysis, correction of antithrombin-3 and blood clotting factors. Correction
      of haemostasis should be done in "pre-non-liver" period and later in "non-liver"
      reperfusion periods.

PMID- 9162768
TI  - [Results of use of sandostatin in pancreatoduodenal resections].
AB  - From February 1995 to July 1996 pancreato-duodenal resection has been performed
      in 12 patients in RCS (7 men and 5 women, mean age 53.6 years). The operation was
      indicated in malignant tumors of the pancreatic head, big duodenal papilla,
      distal part of common bile tract (9 patients); benign diseases of pancreas (3
      patients). Sandostatin (0.3 mg/day for 4-7 days) was used in all cases to prevent
      postoperative pancreatitis and pancreato-jejuno-anastomosis incompetence. The
      levels of alphfa-amylase, blood glucose, leucocytes were monitored, as well as
      the duration of pancreato-jejuno-anastomosis drainage use, rate and seriousness
      of postoperative complications and duration of in-patient treatment. The results
      were compared to a control group, consisting of 6 men and 6 women (mean age 53.8
      years) with malignant tumours of big duodenal papilla, head of the pancreas,
      common bile tract. The use of Sandostatin has decreased the level of alphfa
      amylase in the first postoperative day to 292.8 +/- 152.2 u/l vs. 594.9 +/-
      368.79 in a control group (p > 0.05), duration of the drainage use: 6.1 +/- 1.5
      days vs. 12.9 +/- 7.2 days (p < 0.05). The number and rate of severity of
      postoperative complications were significantly less: 58.3% vs. 100%. The
      frequency of pancreato-jejuno-anastomosis incompetence has decreased 3 times; the
      rate of abdominal cavity abscesses has decreased by 30%, the number of bile tract
      complications has decreased too (1 vs. 2). The rates of postoperative mortality
      were 8.3% in both groups. The use of Sandostatin made it possible to decrease the
      frequency and severity of postoperative complications and decrease the duration
      of in-patient treatment.

PMID- 9162769
TI  - [Surgical treatment of patients with chronic critical ischemia of legs, caused by
      atherosclerosis].
AB  - 208 patients with primary chronic critical ischemia of lower extremities (CCILE)
      were operated on from 1988 to 1995. The criteria of CCILE were the following:
      ischemia of an extremity in rest with specific ischemic pain for more than 2
      weeks; existence of ulcernecrotic changes in distal parts of the extremity;
      brachiommalleous index (BMI) less than 0.35; malleous systolic pressure less than
      50 mm Hg. Functional condition of the patients corresponded to class 3A, B and 4.
      The share of patients with CCILE among patients with lower extremities arterial
      lesions was 35%. In 150 (72%) of them there were lesions of aorto-illo-femoral
      tibio-popliteal segment; in 58 (28%)-damage of a femoral-popliteal-tibial
      segment. The number of patients with trophic changes appear in early stage. 154
      reconstructive operations have been performed in patients with multiple arterial
      lesions higher and lower of the Poupart's ligament, and only one primary
      amputation and sympathectomy. In 63 (42%) of the patients the "two-floor"
      reconstruction has been performed. In 142 (92%) of the cases positive results
      have been achieved. In 78.5% cases the grafts were competent a year after the
      surgery and the extremities were saved in 88% of the patients. 60 reconstructive
      operations, 3 primary amputations and 1 sympathectomy have been performed in
      patients with the lesions, located lower than Poupart's ligament. In 58 (96%) of
      the patients positive results were achieved. One year after surgery the grafts
      patency was 63.5%, and extremities were saved in 79% of the patients. The
      immediate and long-term follow-up results of femoral-politeal and femoral-tibial
      grafting did not differ significantly. Long-term follow-up results were better in
      case of less duration of CCILE before surgery. Adequate revascularisation of the
      extremity is an optimal method of treatment of patients with CCILE.

PMID- 9162770
TI  - [Plastic microsurgery of the fingers defects].
AB  - The experience of plastic operations in small segmental defects of the hand with
      the use of "insular" Litteler's flap has been analysed. Long-term results are
      available for 10 patients. The difference of reception has been found in
      transplanted and recipient's finger. The patients feel the zone of the plasty
      like a donor finger. This causes problems with the operated hand movement
      coordination. In 23 cases the original method of microsurgical technique has been
      used to avoid this effect. The nerve was cut near the transplant edge and then
      sutured with the nerve of recipient finger. Functional results of the modified
      operations are more adequate to the demands of plastic region.

PMID- 9162771
TI  - [Restoration of replanted extremity function with use of microsurgical tissue
      autotransplantation].
AB  - The results of 40 tissue autotransplantations for correction of function of the
      replanted upper extremities. The peculiar features of vascularised tissue
      autotransplantation in specific situations of anatomic and morphologic changes in
      replanted upper extremities are presented. It was proved, that vascularised
      tissue autotransplantation is a safe and effective method for restoration of
      function of the extremities, replanted after traumatic amputation, that was
      accompanied with massive tissue damages. Microsurgical autotransplantation
      expands the indications in replantation surgery and makes it possible to perform
      replantation in cases, when function restoration was considered nonprospective.

PMID- 9162772
TI  - [Storage of cadaver kidney by trans-organ oxygen insufflation].
AB  - Transorganic oxygen preservation was used in storage of 87 cadaver kidneys. The
      kidneys were stored for 14 to 56 h (34 +/- 1.95 on the average). After storage,
      all organs were transplanted to 87 patients with chronic renal insufficiency in
      the terminal stage. The patients age ranged from 18 to 55 years. All recipients
      were divided into 3 groups according to the results of the operation. Group 1 (55
      patients)-the function of the organ was restored immediately, blood creatinine
      normalized on the 5th-10th postoperative day; subsidiary hemodialysis was not
      needed. Group 2 (22 patients)-the function of the transplant was restored 14-21
      days after the operation; 2 to 8 sessions of hemodialysis had to be conducted.
      Group 3 (10 patients)-the transplant did not function due to acute irreversible
      canalicular necrosis or irreversible rejection. No correlative dependence between
      restoration of the transplant function and the duration of storage was noted (r =
      0.15). Our experience allows us to assert that transorganic oxygen perfusion can
      ensure long-term safe storage of cadaver kidneys.

PMID- 9162773
TI  - [Role of membrane protectors and antioxidants in the process of perfusion and
      preservation of donor lungs].
AB  - Comparative study of the effect of four perfusion and preservation solutions on
      lung function, conducted in experiments on 69 inbred dogs, revealed the following
      regular features. Euro-Collins and electrolyte solutions cause a marked increase
      of the capillary-hydrostatic pressure, a significant decrease of colloido-osmotic
      pressure of the plasma, and, as a result, reduction of the ient between them.
      This is manifested by edema of the lungs. The use of LPD solution is attended by
      moderate edema of the lungs in moderately increased capillary hydrostatic
      pressure and mildly reduced colloido-osmotic pressure of the plasma. Perfusion
      and preservation of the lungs with the LPD solution, containing membrane
      protectors and antioxidants, for 12 hours is marked by practically unchanged
      indices of capillary-hydrostatic pressure, plasma coloido-osmotic pressure, and
      the gradient between them. Edema of the lungs does not develop in this case.

PMID- 9162774
TI  - [Lymphogranulomatosis of thymus].
AB  - Six cases of lymphogranulomatosis of the thymus are described. There are few
      clinical sings as a rule or none at all. The main diagnostic method is X-ray
      (poly-position roentgenoscopy, computed tomography) which reveals a new growth in
      the thoracic cavity. Preoperative morphological verification of the character of
      the tumor is difficult. Only histological study shows the true character of the
      disease. Surgical intervention makes it possible to establish the diagnosis and
      is a component of the complex of the therapeutic measures (radiotherapy and
      chemotherapy) applied in the management of local forms of lymphogranulomatosis of
      the thymus.

PMID- 9162775
TI  - [Surgical treatment of purulent complications of acute pancreatitis].
AB  - The results of the treatment of 34 patients with purulent lesions of the pancreas
      and parapancreatic fat are presented. The surgical policy is proposed, depending
      on the location of purulent cavities. The policy includes evaluation of the rate
      of the purulent process dissemination, dissection of the necrotic and nonviable
      tissues and adequate drainage of the parapancreatic fat with subsequent
      aspiration (in 48-72 hours) and irrigation of the cavities starting from the 5
      7th day. The blood vessels, located in purulent zone should be ligated. 26 of 34
      patients have been successfully discharged. Postoperative enteric fistulas have
      developed in 3 patients.

PMID- 9162776
TI  - [The device for placing ligature in deep wounds].
AB  - A special device has been designed to provide safe and convenient placing of a
      ligature to the dissector or clamp in a deep wound. The device contains fork
      shaped working part and a handle. The handle has an obtuse-angle curve and is
      connected with the working part by a hinge. It also has a handler-spring for
      fixing a ligature. The device prevents a chance of damaging nearby tissues in
      placing the ligature that makes it possible to hasten surgery.

PMID- 9162777
TI  - [Choice of method for laparoscopic hernioplasty].

PMID- 9162779
TI  - Jeopardy: using a familiar game to teach health.

PMID- 9162778
TI  - [Ethics of a surgeon].

PMID- 9162780
TI  - [Morbidity, mortality and the potential years of life lost attributable to
      tobacco].
AB  - BACKGROUND: The aim of this study was to evaluate the morbidity and mortality
      attributable to smoking. MATERIAL AND METHODS: A transversal study was performed
      in a reference population of residents of the province of Granada (Spain). The
      number of deaths in 1985, the number of patients admitted to public hospitals in
      1987 and a sample of out patients in 1989 were gathered from the National
      Institute of Statistics and hospital registries, and a prospective collection
      from out patient clinics was also carried out. The diseases studied included:
      oropharyngeal, esophageal, pancreatic, laryngeal, lung, bladder and kidney
      carcinomas, ischemic cardiopathy, cerebrovascular stroke, peripheral arteriopathy
      and chronic obstructive lung disease (COPD). Statistical analysis was performed
      by populational etiologic fraction and the chi square test. RESULTS: Four point
      five percent of the total number of annual hospital admissions, 6.3% of the out
      patients, 15.9% of the mortality and 12.0% of the total number of potential years
      of life lost (TPYLL) were estimated to be attributable to smoking in individuals
      over the age of 15 years in the province of Granada. The most frequent causes of
      morbidity attributable to smoking were COPD and ischemic cardiopathy, and with
      regards to mortality, ischemic cardiopathy (28.5%), COPD (21.6%) and lung cancer
      (17.5%). Higher percentages were observed in males than in females and in the
      group from 46 to 65 years of age. CONCLUSIONS: Smoking is not only responsible
      for an important percentage of deaths, but also leads to premature death and a
      reduction in the quality of life which is translated into an excess of health
      care costs. Since the impact of smoking becomes particularly evident from 46 to
      65 years of age, smoking prevention should be centered on the early years of
      life.

PMID- 9162781
TI  - [The prevalence of and factors associated with falls in older persons living in
      the community].
AB  - BACKGROUND: To describe falls in urban community elderly people and to identify
      factors associated with their occurrence. MATERIAL AND METHODS: Data from an age
      and sex stratified sample of the elderly people living in Leganes (n = 1183).
      Potentially associated factors are explored in bivariate analyses and a
      multivariate logistic regression analysis. The variables are entered into the
      equations in the causal order hypothesized. RESULTS: 14% of the elderly persons
      in Leganes reported at least a fall in the previous twelve months, 41% of them
      had consequences, 19% ended in hospitalization. In the bivariate analyses
      significant positive associations were found with being older than 65, female,
      widowhood, having more than six chronic conditions, functional limitations in
      lower extremities, disability, urinary incontinence and sleep problems. In the
      multivariate model independent associations were observed for females, functional
      limitations of the lower extremities, cognitive deficit, visual impairment,
      urinary incontinence and sleep problems. CONCLUSION: The frequency of falls in
      the elderly population in Leganes, Madrid, is approximately half of that reported
      in international studies using similar methodology. However, associations with
      known risk factors are confirmed in our population. The association between falls
      and difficulties in falling asleep found in this study should be confirmed by
      others.

PMID- 9162782
TI  - [Prognostic factors in the evolution of psoriatic arthritis].
AB  - BACKGROUND: The aim of this study is to determine the evolution and prognostic
      factors in the patients with psoriatic arthritis. PATIENTS AND METHODS: We have
      reviewed retrospectively the follow-up of 96 patients with psoriatic arthritis
      seen in our service. We have collected the following data at onset of the
      disease: age and sex, age at onset of cutaneous and articular manifestations,
      clinical form, distal interphalangeal affection, axial involvement, erythrocyte
      sedimentation rate, rheumatoid factor, antinuclear antibody and HLA antigen.
      Likewise, we have collected the present functional class. We have correlated the
      data at onset of the disease with the present functional class. RESULTS: Mean +/-
      SD age of 96 patients (48 male, 48 female) was 51 +/- 14 years. The majority of
      patients (78%) were in ACR functional class I or II. The most frequent clinical
      form was the oligoarticular (46%), except in the female group, in which the most
      frequent was the symmetric polyarticular one (46%). We found statistically
      significant correlation between the present functional class and the clinical
      form at onset and the disease duration. We didn't found a statistically
      correlation between the present functional class and the axial involvement.
      CONCLUSIONS: Patients with psoriatic arthritis and symmetric polyarthritis are
      more frequently female, and have a worse prognosis. The axial involvement does
      not imply a worse prognosis.

PMID- 9162783
TI  - [Analgesics in the postoperative period of abdominal interventions. The Study
      Group on Postoperative Analgesia of the Spanish Society of Clinical
      Pharmacology].
AB  - BACKGROUND: Analgesics can avoid postoperative pain. The aim of this study was to
      evaluate their prescription after abdominal surgery. PATIENTS AND METHODS:
      Prospective study including patients who had undergone abdominal surgery in two
      hospitals in Barcelona, in 1993. Prescription and administration of analgesic
      drugs, and pain severity during the first 48 hours of the postoperative period
      were evaluated. RESULTS: One hundred and sixty-four patients (83 men) were
      included. The most frequently prescribed drugs were metamizol (111; 68%),
      pethidine (83, 51%), and diclofenac (44; 27%). A high percentage of analgesic
      prescriptions on an "as needed" basis was recorded. Administered doses were lower
      than those recommended, and lower than those prescribed. Fifty-three percent of
      patients suffered significant pain during the first day. CONCLUSION: A too low
      proportion of analgesic drugs is prescribed in a predetermined schedule, in
      contrast to "as needed" prescription. Opiate derivatives are underused. All
      analgesic drugs are prescribed at inadequate dosage. This prescription pattern is
      associated with a high prevalence of postoperative pain.

PMID- 9162784
TI  - [No to tobacco, yes to life].

PMID- 9162785
TI  - [Confidentiality and professional secrecy in the clinical history].

PMID- 9162786
TI  - [Clostridium difficile].

PMID- 9162787
TI  - [Should toponyms be translated?].

PMID- 9162788
TI  - [The antigen associated with squamous cell carcinoma in patients with benign
      hepatopathies].

PMID- 9162789
TI  - [The assessment of anxiety in the surgical anteroom].

PMID- 9162790
TI  - [Spontaneous remission of essential thrombocythemia during pregnancy].

PMID- 9162791
TI  - [Bilateral pulmonary thromboembolism secondary to a double malformation of the
      iliac veins].

PMID- 9162792
TI  - [France. Severe punishment for malpractice].

PMID- 9162793
TI  - [Hospitals in Chechnya. Physicians without salaries pay from their own pocket].

PMID- 9162795
TI  - [If euthanasia will be permitted--what happens?].

PMID- 9162794
TI  - [Compensation for negligence in health care--a guiding verdict of the court of
      appeal in 1996].

PMID- 9162796
TI  - [Delayed fee for insurance certificates].

PMID- 9162797
TI  - [Statistical pitfalls].

PMID- 9162798
TI  - [The economical compensation for participation in clinical trials is modest].

PMID- 9162799
TI  - [A health care politician must do a lot of priorities].

PMID- 9162800
TI  - [Generalization about promiscuity in the African culture].

PMID- 9162801
TI  - [Compensation to lobotomized patients: in Sweden too?].

PMID- 9162802
TI  - [Where did nuclear medicine disappear?].

PMID- 9162804
TI  - [Vaccination against varicella? Older children and adults who were not affected
      by the disease should be vaccinated].

PMID- 9162805
TI  - [Unequal distribution of obstetrical analgesia].

PMID- 9162803
TI  - [A party that wants to save health care].

PMID- 9162806
TI  - [Gene therapy in peripheral vascular disease. A future therapeutic method?].

PMID- 9162807
TI  - [Tonsillectomy in adults is performed as day surgery. Risk assessment and
      experiences from Uppsala].

PMID- 9162808
TI  - [Difference between BO and BOOP! Two lung diseases that are often mixed up].

PMID- 9162809
TI  - [Ambulatory surgery for inguinal hernia. Patients' experiences with simplified
      routines].

PMID- 9162810
TI  - [Should more people be vaccinated against varicella? Time to decide!].

PMID- 9162811
TI  - [Blood exposure during labor. A common risk of contamination that may be
      reduced].

PMID- 9162812
TI  - [Regional courses recruit postgraduate students. Growing interest for continuing
      education and research].

PMID- 9162813
TI  - [More than 6300 cases in a database of health risks. Lex Maria events often
      result in organizational changes].

PMID- 9162815
TI  - [The AT-physicians in Motala: we are needed in health care].

PMID- 9162814
TI  - [Research on women is questioned and misinterpreted all the time. The target is
      change--not frustration].

PMID- 9162816
TI  - [Proposal on an abortion registry with social security number. The scientists
      want to create a basis for epidemiological studies].

PMID- 9162817
TI  - [Recommendations are missing: the part of medical abortions varies between
      hospitals].

PMID- 9162818
TI  - [The existence of centers for the victims of torture is at risk].

PMID- 9162819
TI  - [The new care guarantee is considerate towards more people].

PMID- 9162820
TI  - [Ingenious feedback system benefits recovery].

PMID- 9162821
TI  - [A debate instead of silence in connection with medical errors].

PMID- 9162822
TI  - [New types of education].

PMID- 9162823
TI  - [Does medical education counteract its purpose? The capacity of empathy in
      relation to physician-patient relations is neglected].

PMID- 9162824
TI  - [New WHO recommendations. Hypertension control].

PMID- 9162826
TI  - [The choice of anesthesia methods in abdominal surgery is decisive for patients'
      recovery when it comes to eating again. Opinion should be avoided].

PMID- 9162825
TI  - [New discoveries on metabolic preparation prior to surgery: carbohydrate loading
      is better than fasting].

PMID- 9162827
TI  - [Revised guidelines on fasting prior to anesthesia: now is the patient allowed to
      drink. Swedish Society of Anesthesiology].

PMID- 9162828
TI  - [Correction of myopia--eyeglasses, lenses, laser].

PMID- 9162829
TI  - [Myopia is not only hereditary. Environmental factors are significant].

PMID- 9162830
TI  - [Cataract surgery is a savings-box. Important to perform surgery early].

PMID- 9162831
TI  - [Instructions in empathy should be introduced early in the training especially
      for male medical students].

PMID- 9162832
TI  - [Deficient concordance worries forensic psychiatry. Increased cooperation between
      psychiatrists and clinics is needed].

PMID- 9162833
TI  - [New Nordic nutritional recommendations on hard fats. The intake should be
      limited to ten energy per cents].

PMID- 9162834
TI  - [Suicide and SSRI preparations. Antidepressive agents without psychotherapy are
      more hazardous than beneficial].

PMID- 9162835
TI  - [Free radicals and antioxidants].

PMID- 9162836
TI  - [Infections caused by enterohemorrhagic Escherichia coli strains].

PMID- 9162837
TI  - [Coronary heart disease--a free radical associated disease? What is the value of
      antioxidant substances?].

PMID- 9162838
TI  - [Physical activity prevents cardiovascular diseases. Consensus conference of the
      National Institute of Health].

PMID- 9162839
TI  - [Alcohol--protection or risk for the heart?].

PMID- 9162840
TI  - Varicella-related deaths among adults--United States, 1997.
AB  - During January-April 1997, state health departments reported three fatal cases of
      varicella (chickenpox) to CDC. All three cases occurred in young adult women who
      were unvaccinated and susceptible to varicella and who were infected by exposure
      to unvaccinated preschool-aged children with typical cases of varicella. This
      report summarizes these three cases, which indicate that preventable varicella
      related deaths continue to occur in the United States. In addition, the report re
      emphasizes the recommended strategies for preventing varicella.

PMID- 9162841
TI  - Tornado-associated fatalities--Arkansas, 1997.
AB  - On March 1, 1997, approximately nine tornadoes originating from two separate
      thunderstorms swept across Arkansas, from Hempstead County in the southwest to
      Clay County in the northeast (approximately 260 miles). The tornadoes caused 26
      deaths and an estimated $115 million in property damage, reflecting damage to
      residences, nonresidential buildings, bridges, and roads and agriculture and
      timber losses. The strongest tornadoes touched down southwest of Little Rock in
      Clark, Saline, and Pulaski counties; the estimated widths of the tornado paths
      ranged from 1/2 to 1 mile, and wind speeds were > 200 miles per hour (National
      Weather Service [NWS], unpublished data, 1997). This report summarizes
      circumstances of the tornado-associated fatalities from information collected by
      the American Red Cross (ARC); 14 of the 26 fatalities occurred among persons who
      were in mobile homes.

PMID- 9162842
TI  - Sustained transmission of nosocomial Legionnaires disease--Arizona and Ohio.
AB  - In 1996, two hospitals reported sustained transmission of nosocomial Legionnaires
      disease (LD). The hot water distribution systems in each hospital were implicated
      as the sources of infection. This report summarizes investigations in these two
      hospitals by hospital personnel, state and local health officials, and CDC and
      efforts to control transmission.

PMID- 9162843
TI  - Cancer screening offered by worksites--United States, 1992 and 1995.
AB  - Since the early 1970s, many U.S. businesses have implemented worksite health
      promotion programs to help contain employer health-care costs; improve employees'
      health status, productivity, and morale; reduce absenteeism and employee
      turnover; and provide a convenient setting for screening and education. Because
      approximately 130 million persons in the United States work, the worksite is an
      effective location for offering health screening and educational programs
      otherwise unaccessible to at-risk persons. From the late 1980s to the early
      1990s, the prevalence of worksite health promotion activities increased in the
      United States. To characterize more recent national practices in worksite-based
      cancer screening programs, CDC examined data from two national probability
      surveys--the Office of Disease Prevention and Health Promotions's (ODPHP's) 1992
      National Worksite Health Promotion Survey and CDC's 1995 Worksite Benchmark
      Survey. This report summarizes the results of the analysis, which indicate that,
      in contrast to previous findings about worksite health promotion in the 1980s,
      the prevalence of worksites offering cancer screening declined from 1992 to 1995.

PMID- 9162844
TI  - [140 years Nederlands Tijdschrift voor Geneeskunde. 140 volumes: looking back,
      looking in and looking forward].
AB  - The Nederlands Tijdschrift voor Geneeskunde was founded in 1856 when five of the
      nine medical journal in the Netherlands decided to join hands and launch a new
      medical weekly (in Dutch). About 800 manuscripts are now submitted each year,
      most of which are peer reviewed before acceptance. The editorial board consists
      of about twenty medical specialists who have agreed to carry out the bulk of the
      peer review for a period of three years each. After retirement from the editorial
      board, they are a lifelong member of the Association of the Dutch Journal of
      Medicine. After acceptance, articles are thoroughly scientifically and
      linguistically edited to ensure that the general medical readership will
      understand them. About 50% of the accepted papers are published within twenty
      weeks. In the near future the journal pages will have more illustrations and more
      coloured ones, educative panels, and a digest of Dutch research published in
      international journals.

PMID- 9162845
TI  - [Surgery in the last 40 years: looking back in wonder].
AB  - Much has changed in surgery in the last 40 years: From the fifties, new findings
      were introduced, such as antibiotics, anticoagulants, cytostatics, cardiac and
      pulmonary surgery, artificial respiration, osteosynthesis, arteriography,
      synthetic fibres and image intensifying in the clinic. The average hospital stay
      in the surgical ward used to be 21 days, mortality 6-7%. Owing to the long
      hospital stays, nurses, physicians and interns grew familiar with the pre- and
      postoperative courses. In the sixties, reconstructive vascular surgery became
      possible, where earlier limbs had to be amputated. The first pacemakers were
      inserted. There was widespread lung surgery because of tuberculosis, and owing to
      the great poliomyelitis epidemic of 1953, there was ample expertise of artificial
      respiration. Surgical treatment of fractures took off, and the first hip
      prostheses were introduced. The average hospital stay shrunk to about 14 days and
      the mortality to less than 2%. A turning point in surgical management came in
      1961. In that year, the free Saturday was introduced, marking a transition from
      austerity to luxury. The medical successes were overtaken by the patients' needs,
      expectations and claims. Physicians started to work fixed hours, rather than when
      required. The seventies saw the beginning of intensive care and great progress in
      paediatric surgery; organ transplantation came in the eighties. The recent years
      were marked by formalization and protocolling of treatment and information. The
      growing influence of the government and of bureaucracy, and the encroachment upon
      the surgeon's social position and income interfere with his work with the
      patients.

PMID- 9162846
TI  - [Obstetrics and gynecology in the last 40 years].
AB  - In the Netherlands the last 40 years have seen major changes in obstetrics and
      gynaecology: Progressive expansion of evidence-based medicine. A measurable,
      greatly improved quality policy during gynaecologists' training and the
      subsequent period. Increase of diagnostic possibilities during pregnancy (such as
      real-time echography, Doppler measurements, amniocentesis and umbilical-cord
      puncture). Foundation of the Landelijke Verloskunde Registratie (LVR. National
      Obstetrical Registry) in 1982, in which by now 90% of the specialists and 80% of
      the midwives are participating. Implementation of the 'Dutch model' of
      obstetrical care. Decrease of the number of home deliveries and increase of the
      obstetrical interventions. More attention for sex problems. Better results in the
      treatment of gynaecological tumours. Great progress in the field of reproduction
      endocrinology (both pharmaceutical and surgical).

PMID- 9162847
TI  - [Automation of medical literature--and information services].
AB  - It is important for clinical practice to be able to find (or retrieve) relevant
      literature and to keep informed of the state of medical science. The fact that
      the contents of articles in journals are now accessible via computers is the
      result of integration of bibliographic techniques, medical knowledge and computer
      technology. Articles published in some 5000 medical journals can nowadays be
      retrieved electronically via Medline and Embase together (but medical literature
      in Dutch is underrepresented). Computerised insertion of publications into
      Internet dose not make information traceable or accessible, let alone reliable
      and readable. It cannot be predicted if electronic versions of scientific
      periodicals will replace the printed editions completely. However, valuable,
      reliable information will always have its price, even on Internet. It is unlikely
      that electronic information published privately (internet) will replace
      scientific publishers soon, for readers will still want selection and monitoring
      of contents and language. Good layout, professional typography and suitable
      illustrations to enhance reading comfort and cognitive processes, will even
      become more important. The problems arising from the immensity of scientific
      knowledge are not (any longer) of a technological nature-what is needed is a
      cultural about-turn of the information infrastructure in medical-scientific
      associations, organizations and institutions.

PMID- 9162848
TI  - [Editing of articles accepted for publication by the Nederlands Tijdschrift voor
      Geneeskunde].
AB  - The Nederlands Tijdschrift voor Geneeskunde has been publishing medical science
      in Dutch for 140 years. To bridge the gap between the specialist science and the
      general medical reader several sections in the accepted papers have to be
      clarified, simplified and shortened by post acceptance editing. The style and
      language of the authors is treated with respect. Changes are made if the article
      does not comply with internationally accepted rules on scientific reporting, if
      the article can not be understood using currently authoritative general and
      medical books of reference, and if its language does not comply with generally
      accepted Dutch rules for grammar and spelling.

PMID- 9162849
TI  - [Physicians as connoisseurs and teachers in practical clinical education: good
      example engenders good following].
AB  - There is theoretical knowledge (of facts) and there is knowledge that might be
      described as 'synthetizing ability resulting from experience': the clinical eye,
      pattern recognition, intuition, art. Experienced GPs, for instance, in
      formulating hypotheses, make much use of contextual information and patients
      characteristics such as occupation, social connections, housing situation and
      consumption of tobacco and alcohol. Owing to their great experience with
      patients, they know how to handle such contextual information more effectively
      than recently graduated MDs. They are, however, unable to state explicitly how
      they do this. There are always mental steps that stubbornly refuse to submit to
      logical step-by-step reconstruction. How can this practical knowledge be taught?
      The master-apprentice situation serves this purpose well: the student not only
      practises on his or her own, but also sees an experienced doctor at work and can
      exchange ideas with him or her about the how and why of medical activities.
      Uncertainty plays a major part: doubt is not a sign of incompetence, but
      constitutes the essence of clinical action.

PMID- 9162850
TI  - [Medical science in the Dutch language].
AB  - Medical researchers consider a publication in English to be of a higher standard
      than one in a local language such as Dutch. An international publication in
      English is appropriate when the readers addressed belong to an international
      scientific community, but the mere fact that a publication is in English is no
      indication of its importance. Research of a national scope and of national
      consequences should be published in the national native language. In addition the
      use of the mother tongue allows deeper and more balanced thought in comparison to
      the use of a second language. The application of study results in clinical
      practice in the Netherlands is enhanced by their publication in Dutch, as is the
      national recognition of the research group. Finally, articles in Dutch provide
      all of the Dutch clinicians with the opportunity to read original scientific work
      and not via a (popular) translation. This contributes to science-based clinical
      medicine in the Netherlands.

PMID- 9162851
TI  - [The clinical lesson in the Nederlands Tijdschrift voor Geneeskunde in the last
      40 years].
AB  - 'Lessons of the Week' have been published in Nederlands Tijdschrift voor
      Geneeskunde since 1928. They consist of a clinical patient demonstration on paper
      but with the structure and the wording appropriate for a college theater. These
      lessons are read by three quarters of the journal's readership. They are usually
      written by senior clinicians.

PMID- 9162852
TI  - [Original articles in the Nederlands Tijdschrift voor Geneeskunde in the last 40
      years].
AB  - Original articles offer the reader of the Nederlands Tijdschrift voor Geneeskunde
      information about Dutch scientific research. These readers are selective but
      appreciative. The emphasis has shifted in the last 40 years from case histories,
      introduction of new techniques, literature studies and opinions, to qualitatively
      and methodologically adequate numerical studies, with strictly arranged
      presentation. The numbers of patients per study have increased substantially, and
      statistical processing has grown more extensive. Cost-benefit analyses appeared.
      The number of prospective studies remained constant.

PMID- 9162853
TI  - [A quarter of a century of computer-assisted anticoagulant treatment].
AB  - Twenty-five years ago the computer was introduced to assist the dosage
      calculation in the Dutch anticoagulation services. Many of the laboratory
      findings in patients treated by anticoagulants can be quantitated and may be used
      to construct a computer dosage algorithm.

PMID- 9162854
TI  - [Is smoking cigars and pipes harmful?].

PMID- 9162855
TI  - [Age at menopause as risk factor in cardiovascular mortality].

PMID- 9162856
TI  - [From happy to worrisome expectation? Various ethical problems concerning the
      triple test].

PMID- 9162857
TI  - [Prenatal diagnosis for trisomy 21: triple test more efficient than age
      criterion].

PMID- 9162858
TI  - [Role of perinuclear antibodies against cytoplasm of neutrophilic granulocytes (p
      ANCA) in the diagnosis of vasculitis and chronic inflammatory diseases].

PMID- 9162859
TI  - [Diagnosis and therapy of hypertension with renal artery stenosis].

PMID- 9162860
TI  - [Diagnosis and therapy of hypertension with renal artery stenosis].

PMID- 9162861
TI  - [The 'Seven Countries Study': 40 years of research in coronary heart diseases in
      7 countries].
AB  - In the Seven Countries Study, which was started in 1958, the risk factors of
      coronary heart disease are studied in a large number of men. The study still runs
      and the results also provide insight in the relation between life style and
      health in elderly people.

PMID- 9162862
TI  - [Internal medicine in the last 40 years].
AB  - Internal medicine in the last 40 years has known many eminent teachers at
      universities, such as Hijmans van den Bergh, Van Buchem, Borst, Mulder,
      Lindeboom, De Langen, Hulst, Jordan, Formijne, Major, Snapper, Groen and Querido,
      and others outside universities such as Stuyt, Van Hees, Eindhoven, Pannekoek,
      Schalm, Bruins Slot, Heeres, Stolte and Pompen. The main scientific platform on
      which the bequeathors assembled in the first few decades after World War II was
      the Algemene Ziektekundige Vereniging ('General Medical Association'), which met
      in Utrecht. Important medical steps forward in that period were the virtually
      complete eradication of tuberculosis in the Netherlands, the developing of
      vaccines against smallpox and polio, but also against the various types of virus
      hepatitis, and the progress in intensive care, transplantation and molecular
      biology. The Nederlandsche Internisten Vereeniging ('Dutch Association of
      Internists') has had its own scientific journal since 1958. Essentials in modern
      internal medicine are appropriate care and demonstrated usefulness of a treatment
      (evidence-based medicine); standards, values and ethics are core issues, as are
      quality control and cost control. Change is also in progress in the doctor
      patient relationship, as manifested in the Wet Geneeskundige
      Behandelingsovereenkomst ('Medical Treatment Accord Act').

PMID- 9162863
TI  - Omental transposition for Alzheimer 's disease.
AB  - A patient with Alzheimer's disease of long standing was treated with omental
      transposition to his brain. The rational for the procedure was to use the omentum
      to increase cerebral blood flow and to augment cholinergic neurotransmission
      activity. The patient improved for a year following surgery but after that time
      slowly began to decline neurologically and cognitively. However, according to
      Alzheimer's specialists who have followed the patient pre and postoperatively, he
      still maintains, 2.5 years after surgery, a higher level of performance than
      expected. There is theoretical and now a clinical suggestion that the omentum
      might play some role in the treatment of Alzheimer's disease. In view of the
      devastating nature of the disease, it seems reasonable to suggest that a limited
      controlled study be carried out to support or negate the benefit of the
      operation.

PMID- 9162864
TI  - Bilateral common carotid artery occlusion with minimal neurological deficit: long
      term follow up in 3 patients.
AB  - Three patients, two women and one man, aged 56-70 year (mean 59 years) with
      modest neurological deficits and bilateral occlusion of the common carotid
      arteries initially identified by duplex scanning and angiography were followed by
      repeated clinical and transcranial Doppler examination (TCD) over 6.5 years.
      Vasomotor reactivity (VMR) was tested by combined examination of TCD and xenon
      133 cerebral blood flow (CBF) before and after intravenous administration of 1 g
      acetazolamide. At follow-up CBF was measured using single photon emission
      computerised tomography (SPECT). In two patients mean velocities in the middle
      cerebral artery (MCA) were within the normal range at repetitive examinations
      with good VMR ranging 30-111%, whereas CBF was reduced in MCA territories ranging
      29-36 ml 100 g(-1) min(-1), but increasing 44-69% after acetazolamide, indicating
      good VMR. These 2 cases had anterograde flow in the ophthalmic artery and siphon.
      The third patient had very low MCA mean velocities of 21-27 cm sec(-1),
      increasing 26-33% after acetazolamide. This patient had retrograde flow in the
      ophthalmic artery and siphon connected with bilateral prolonged episodes of
      amaurosis fugax and transient ischemic attacks. In all three patients the
      posterior cerebral arteries were major supplying collaterals having high mean
      velocities of about 100 cm sec(-1) and high velocities in the basilar arteries of
      85 cm sec(-1) as well. During follow up no patient had a new stroke, but all
      experienced orthostatic dizziness and chronic fatigue.

PMID- 9162865
TI  - Microsurgical anatomy of the infratentorial trabecular membranes and subarachnoid
      cisterns.
AB  - The understanding of the anatomy of the subarachnoid cisterns and trabecular
      membranes is of paramount importance in the surgical treatment of pathology of
      the posterior fossa. Aneurysms, arteriovenous malformations, and some tumors
      should be approached through the subarachnoid space. The subarachnoid cisterns
      provide natural pathways to approach neurovascular and cranial nerve structures.
      The microsurgical anatomy of the infratentorial subarachnoid cisterns was studied
      in twenty adult brains, using the 'immersion technique'. Air was injected into
      the subarachnoid cisterns and brains were dissected under the operative
      microscope. Six main compartmental trabecular membranes were identified in the
      infratentorial level. They divide the subarachnoid space into six cisterns.
      Cisternal divisions and the disposition of the trabecular membranes were closely
      related to the vascular divisional patterns of the principal arteries. Thorough
      knowledge of the microsurgical anatomy of the subarachnoid space will aid
      neurosurgeons during the surgical approach of many vascular and tumoral lesions
      located in the posterior fossa.

PMID- 9162866
TI  - Rate constant of gadolinium (Gd)-DTPA transfer into chronic subdural hematomas.
AB  - Gadolinium (Gd) DTPA concentrations in subdural fluid and arterial blood were
      measured following intravenous Gd-DTPA injection by ion coupled plasma emission
      spectrometry in 31 chronic subdural hematomas and 12 with subdural effusions.
      Dynamic biological modeling analysis was used to calculate the unidirectional
      transfer rate constant (K) for Gd-DTPA influx into the subdural fluid. The Gd
      concentrations in subdural hematomas and subdural effusions were 36.3 +/- 3.7
      nmol ml(-1) and 80.0 +/- 14.0 nmol ml(-1), respectively. The transfer rate
      constants (K) for subdural hematomas and subdural effusions were 12.4 +/- 1.5
      (x10(-4)) min(-1) and 19.7 +/- 2.2(x10(-4)) min(-1), respectively. The Gd
      concentration and transfer rate constant for subdural effusions were
      significantly (p<0.05) higher than for subdural hematoma. The Gd transfer rate
      constant was significantly correlated with the interval from head injury to
      operation. The present study shows that the immature outer membrane has a high
      transfer rate constant, allowing extravasation of plasma components into the
      subdural space and increasing the volume of the subdural effusion; the rate
      constant decreases with aging of the subdural hematoma.

PMID- 9162867
TI  - A false traumatic giant aneurysm of the supraclinoid carotid artery. A case
      report and review of the literature.
AB  - A patient presented with left hemiparesis and facial palsy developed 20 days
      after a traffic accident. A computerized tomography (CT) scan revealed right
      suprasellar mass lesion. A repeated CT scan revealed a growing mass. Carotid
      angiogram demonstrated a giant aneurysm of the supraclinoid internal carotid
      artery (ICA) with no distal filling. Formation of the aneurysm was thought to be
      due to an overstretching or torsion of the artery or tearing of the ICA by nearby
      prominent bony structure since no basal skull fracture was detected in the plain
      skull film or CT scans. The aneurysm was treated by intracranial trapping of the
      ICA. We present this patient's findings and review previously reported cases in
      the literature.

PMID- 9162868
TI  - Subclavian artery aneurysm associated with absence of the ipsilateral internal
      carotid artery.
AB  - A 48-year-old male presented with a rare subclavian artery aneurysm associated
      with absence of the ipsilateral internal carotid artery. The aneurysm was
      resected and replaced with a Gore Tex artificial graft. Computed tomography,
      angiography and cerebral blood flow findings suggest that defect of the right
      internal carotid artery occurred in the developmental stage. There was no past
      history of trauma, nor histological evidence of inflammatory or sclerotic changes
      in the aneurysmal wall. The two vascular lesions may have been influenced by a
      synchronous causative factor in his developmental stage.

PMID- 9162869
TI  - Symptomatic subacute subdural hematoma associated with cerebral hemispheric
      swelling and ischemia.
AB  - A 55-year-old man with traumatic acute subdural hematoma (SDH) was managed
      nonsurgically because of having isolated mild headache that resolved within a
      week. However, the patient developed an acute onset of amnestic aphasia 12 days
      post-trauma. Although the SDH itself did not increase in volume, remarkable
      swelling of the ipsilateral cerebral hemisphere was observed on CT scanning.
      Craniotomy was required since the main component of the SDH was solid and
      partially organized. Post-operative recovery from his speech disturbance was
      delayed, necessitating speech therapy for more than two months. Additionally,
      decreased cerebral blood flow on the affected side was observed even 3 months
      after injury. Symptomatic subacute SDH exclusively presenting as focal
      neurological deficits, though very rare,is worthwhile to be kept in mind as a
      pitfall in nonsurgical management of acute SDH.

PMID- 9162871
TI  - Microvascular anatomy of striate vessels in dogs: contribution to an experimental
      model of forebrain ischemia.
AB  - Basal perforating vessels such as Heubner's artery are involved in various
      arteriopathic conditions resulting in cognitive and memory deficits. In order to
      evaluate if a model of focal forebrain ischemia can be obtained in dogs, a
      systematic study of the microvascular anatomy of the striate vessels was
      performed using intravascular injections of acrylic paint and/or India ink.
      Medial and lateral striate arteries were identified and found distinct either by
      their superficial anatomy as well as their deep perfusion territories. One medial
      striate artery emerging consistently from the junction of the A1 segment of the
      anterior cerebral artery and the ethmoidal artery resembles the human recurrent
      artery of Heubner. Therefore, the dog may provide a suitable model of forebrain
      ischemia involving solely the perfusion territory of the medial striate arteries.

PMID- 9162870
TI  - Hemodynamic alterations in focal cerebral ischemia: temporal correlation analysis
      for functional imaging.
AB  - We describe a novel approach for analysing the hemodynamic alterations that
      result after focal cerebral ischemia. This approach utilizes a temporal
      correlation analysis of first pass transit data obtained with functional imaging.
      First pass transits of injected contrast agents are measured with dynamic CT
      scanning. Normal transit profiles are obtained from contralateral cortical
      regions to serve as reference profiles. Normalized correlations are then
      calculated to compare transit profiles from each individual pixel within the
      brain to the normal reference profile. The normalized correlation coefficient is
      used as a measure of temporal similarity to quantitatively assess deviations from
      normal hemodynamics. The method is based on the premise that perturbed
      hemodynamics are manifested as changes in the shape of the cerebral transit
      profiles. Correlation maps are produced that display regional alterations in
      cerebral hemodynamics. Results from rabbit (n=4) and rat (n=4) models of focal
      ischemia are presented. In the normal contralateral hemisphere, correlation
      values range from 0.83-0.93 with coefficients of variation of less than 3-4% .
      The ischemic core is comprised of regions without significant bolus transit. The
      peripheral zones that lie between normal brain and the ischemic core are composed
      of intermediate correlation values. By setting statistical thresholds (mean minus
      2SD, p < 0.05), we quantitatively define these intermediate zones as the
      hemodynamic penumbra, i.e. regions where the shape of the first pass transit
      profile has been altered. The resulting correlation maps clearly image gradients
      of altered cerebral hemodynamics. Perfusion indices calculated based on transit
      profile peaks revealed that the penumbral zones possess reduced perfusion on the
      order of about 40 percent of contralateral values. In summary, we believe that
      temporal correlation analysis of first pass transit profiles can be used to image
      the hemodynamic penumbra in focal cerebral ischemia.

PMID- 9162872
TI  - MCA flow asymmetry is a marker for cerebrovascular disease.
AB  - Utilizing the UIC Vascular Laboratory Registry, we retrospectively analysed the
      significance of side to side middle cerebral artery (MCA) flow velocity
      differences. Side to side differences > 15 percent measured by transcranial
      Doppler were considered asymmetric. Asymmetric subjects had 5 times greater
      chance of having significant cervical carotid narrowing on either side on Duplex
      Doppler and a 3.7 times greater chance of having a stroke on brain CT or MRI. MCA
      flow velocity asymmetry is a marker for underlying carotid disease and stroke.

PMID- 9162874
TI  - IB4, a monoclonal antibody against the CD18 leukocyte adhesion protein, reduces
      intracranial pressure following thromboembolic stroke in the rabbit.
AB  - Neutrophil activation and accumulation as a consequence of cerebral ischemia
      reperfusion has been suggested to exacerbate tissue injury. The current study is
      designed to examine the effect of IB4, a monoclonal antibody directed against the
      neutrophil adhesion protein, CD18, in a rabbit model of thromboembolic stroke.
      New Zealand rabbits (3-3.5 kg n=8 each group), were given an autologous clot
      embolus, delivered to the anterior circulation of the brain via the internal
      carotid artery. Immediately following thromboembolism, the mean arterial pressure
      in all animals was reduced to 30 mmHg by controlled exsanguination for a period
      of 45 min. All animals were mechanically ventilated and following parameters were
      monitored hourly: arterial blood gases, intracranial pressure, regional cerebral
      blood flow, hematocrit, and core temperature. Rabbits were given either IB4 (1 mg
      kg(-1)), or vehicle (1 percent albumin, IV) 30 min following the thromboembolic
      event. The mean arterial pressure of all animals was restored to the baseline
      value of 50-60 mmHg for the remainder of the 4-h experiment. Following the
      thromboembolic event, the intracranial pressure rose in both groups, although
      this was significantly less in the IB4-treated group, with the final values being
      195.9 +/- 38.3 vs. 135.5 +/- 26.0 percent of baseline (mean +/- SEM, p < 0.05).
      However, regional cerebral blood flow and infarct size (TTC staining) were
      virtually identical in both groups. It is concluded that blockade of the
      neutrophil adhesion protein, CD18, may contribute to a reduction in the
      intracranial pressure following cerebral ischemia and reperfusion, providing
      further evidence that activated neutrophils may contribute to cerebral edema.

PMID- 9162873
TI  - Deprenyl and pergolide rescue spinal motor neurons from axotomy-induced neuronal
      death in the neonatal rat.
AB  - It has been reported that both the monoamine oxidase inhibitor, deprenyl and the
      dopamine receptor agonist, pergolide have neuroprotective actions. To investigate
      the effect of deprenyl and pergolide on axotomized motor neuron death, we
      examined the survival of spinal motor neurons after sciatic nerve transection in
      the neonatal rats. Newborn rats were anesthetized with hypothermia. Sciatic nerve
      was cut near the obturator tendon in the left thigh. Animals were then treated
      daily with deprenyl (10 mg kg(-1)), pergolide (5 mg kg(-1)), or PBS for 14 days
      with intraperitoneal injections in a blind fashion. After the treatment, the
      number of spinal motor neurons in the L 4-6 was counted. There was approximately
      a 50% loss of spinal motor neurons in PBS-treated group. By contrast, both
      deprenyl and pergolide prevents spinal motor neuron death after axotomy Co
      administration of deprenyl and pergolide is more effective than either agent
      alone but not significant. These findings are consistent with the idea that
      deprenyl and pergolide are survival factors for developing spinal motor neurons.

PMID- 9162875
TI  - Tumor necrosis factor-alpha (TNF-alpha)-induced optic neuropathy in rabbits.
AB  - Both in vitro and in vivo studies have implicated a role for tumor necrosis
      factor-alpha (TNF alpha) in various demyelinating diseases, including HIV-related
      encephalopathy. To investigate whether intravitreal TNF alpha can induce optic
      nerve axonal damage in a rabbit eye model, fifteen rabbit eyes were initially
      injected with TNF alpha (final concentrations: 2U, 20U, and 200U respectively)
      and studied at varying time intervals for up to 24 weeks post-injection, using
      light and electron microscopy. Control optic nerves (no injection or diluent
      injection only) had normal myelinated axons and glia; the myelinated regions,
      neural retina, retinal glia and vasculature of control retinas were normal. In
      TNF alpha-exposed optic nerves, intact, degenerating and demyelinated axons were
      interspersed. Astrogliosis was present, particularly from 8 weeks p.i. and was
      noted up to 24 weeks. Oligodendrocytes were not severely affected in TNF alpha
      exposed optic nerves, and activated macrophages or microglia were not obvious.
      Axonal degeneration was visible among the more superficial myelinated fibers in
      TNF alpha-exposed retinas however the neural retina glia were unaffected. These
      observations suggest that the axonal degeneration induced in TNF alpha-exposed
      rabbit optic nerves over a 24 week period was most likely related to direct
      effects of TNF alpha on optic nerve axons, and not primarily due to anterograde
      degeneration from retinal lesions. In-so-far as neurological pathology in
      general, and optic nerve degeneration in particular, has been described in AIDS,
      and TNF alpha levels may be elevated in this disease, it is of great clinical
      significance that TNF alpha has the capacity to mediate neuronal or axonal
      injury. If so, strategies to block or inhibit TNF alpha can be pursued for
      treatment for the neurological symptoms of AIDS.

PMID- 9162876
TI  - Effects of graded hypothermia on outcome from brain ischemia.
AB  - The effects of mild (34 degrees C) and moderate (31 degrees C) hypothermia on the
      electroencephalogram, cerebral blood flow and outcome from incomplete brain
      ischemia were compared to normothermia (37 degrees C) in the rat. Rats were
      anesthetized with fentanyl (25 mu g kg(-1) h(-1)) and 70 percent nitrous oxide in
      oxygen. Ischemia was produced by right carotid ligation combined with hemorrhagic
      hypotension to 25 mmHg for 30 min. CBF was measured in the right parietal cortex
      by laser Doppler. Neurologic outcome was measured daily for 3 days after ischemia
      and histopathology determined at the end of the study. Before ischemia, neither
      EEG nor CBF were changed by hypothermia compared to normothermic controls. Total
      EEG and beta EEG (12.5-32 Hz) were abolished and CBF decreased by 70 percent
      during ischemia. During a 2.5 h recovery period total EEG and beta EEG activity
      recovered better with moderate hypothermia compared to normothermia. Recovery of
      cerebral blood flow was not significantly different between the treatment groups.
      Neurologic and histopathologic outcome were improved in rats receiving moderate
      hypothermia compared to normothermic controls. These results show that during
      severe incomplete ischemia, hypothermia has a graded effect on outcome which is
      consistent with its effects on brain metabolism.

PMID- 9162877
TI  - Clinical usefulness of 3-D CT endoscopic imaging of cerebral aneurysms.
AB  - Usefulness of endoscopic imaging of cerebral aneurysms is presented. 3-D luminal
      images were obtained using a new processing technique which extracts CT numbers
      in the boundary region between the vessel wall and contrast media filled in the
      vascular lumen. Clinical application of this technique to complicated large
      cerebral aneurysms showed that, with this 3-D CT endoscopic imaging, anatomical
      details of cerebral aneurysms such as the orifice of the aneurysm, intraluminal
      thrombus, and calcification of the wall could be clearly demonstrated. Using a 3
      D imaging method by Helical CT virtual views of various surgical approaches were
      compared preoperatively. With this technique, not only virtual surgical views of
      aneurysms and related vasculature, but also surgical views after virtual
      resection of skull base bone to a desirable extent are freely available. We
      operated on two large, complicated aneurysms and one broad-based aneurysm after
      obtaining 3-D CT endoscopic images of the aneurysms. Such information was found
      to be very useful for determining difficult and complicated cerebral aneurysms
      and broad-based aneurysms for coil embolization or direct open surgery.

PMID- 9162878
TI  - [Carcinoma of the endometrium: a neoplasm on the increase. Its staging and
      treatment: a proposed protocol].
AB  - Endometrial cancer staging is obtained by the analysis of the surgical
      pathological parameters. Therefore, surgery represents the first approach to this
      neoplasia. Surgical-pathological data analysis informs us of the main prognostic
      factors and the spread of the disease. On the basis of these findings, the risk
      of recurrence can be estimated and adjuvant treatments can be planned. A protocol
      for staging and treatment of endometrial carcinoma has been designed by the
      authors. After surgery, adjuvant therapy (chemotherapy or radiotherapy or the two
      modalities combined) is suggested by analysis of the prognostic factors. The aim
      of the protocol is to increase the relapse-free survival and to improve the
      quality of life of endometrial cancer patients.

PMID- 9162879
TI  - [Cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV)
      infection].
AB  - Many studies have shown a strong correlation between CIN and HPV infection.
      Molecular biology has allowed identification of types of HPV which seem to be
      connected, more frequently than others, to dysplastic lesions. Physical state of
      HPV-genome seems to play an important role in the development of cervical cancer.
      In this study the HPV-genome has been searched in tissue specimens obtained from
      34 women affected by CIN II and III. All patients underwent laser conization.
      Immediately before treatment, colposcopically directed biopsies of the cervical
      lesion and of the areas with no colposcopically apparent disease were taken and
      on these samples, HPV-DNA has been searched, isolated and analysed for HPV types
      and physical state. Histologic examination on cones showed 6 cases of CIN II (3
      with HPV), 24 cases of CIN III (14 with HPV), 1 microinvasive carcinoma and 3
      with no residual lesion. Southern blot analysis detected HPV-DNA in 4 cases of
      CIN II (16.7%) and in 20 cases of CIN III (70.6%). In 50% of CIN II and 85% of
      CIN III HPV 16 DNA has been found and in the remaining 50% of CIN II and 15% of
      CIN III HPV 31 DNA has been detected. All CIN II and 14 cases of CIN III showed
      episomal HPV-DNA. Integrated HPV-DNA has been found in 3 cases of CIN III and the
      other 3 cases of CIN III showed both integrated and episomal HPV-genome.
      Integrated form has been noticed only for HPV 16 type. In no case of
      colposcopically normal tissue has HPV-DNA been found. These data seem to confirm
      the strong correlation between HPV 16 type, which often has integrated form, and
      CIN III strengthening the hypothesis of its potential oncogenic action.

PMID- 9162880
TI  - [Bacterial vaginosis and premature membrane rupture: an open study. Preliminary
      data].
AB  - We tried to identify a correlation between bacterial vaginosis and PROM with the
      aim of proposing a future screening for pregnant women at risk for premature
      rupture of membranes. We made two vaginal bacteriological tests on women pregnant
      at 24th and 34th week, and we repeated the same test when it proved positive for
      infection after therapy. We did 375 tests and our study group was composed of 249
      pregnant women, aged between 24 and 35. We also evaluated some variable factors
      as ultrasonographic gestational age redetermination, number pregnancies of oral
      contraceptives or IUD use, presence of risk factors presence (recurrent abortion,
      previous PROM, glucose metabolism alteration, immunosuppression, condylomatosis).
      171 tests proved positive (total positivity percentage: 47.2%). The most common
      micro-organism was Ureaplasma urealyticum (49.1%) that was related to PROM in
      66.7%. This result contracts with affirmations of some England authors who think
      that Ureaplasma hasn't an important role in PROM. This fact, if related to the
      other data we obtained with our study, actually current, shows a strict
      correlation between PROM and bacterial vaginosis, but also a different
      distribution of vaginal infections in our country in comparison with English
      countries.

PMID- 9162881
TI  - [Echography and hysteroscopy. 2 diagnostic technics compared in the
      identification of endometrial lesions in the postmenopause].
AB  - METHODS: In this study we compared ultrasonographic scanning of the endometrium
      and the hysteroscopic view with histology obtained by endometrial biopsy.
      RESULTS: Forty six postmenopausal women were studied, 25 symptomatic and 21
      asymptomatic. In 24 cases endometrial thickness was > 5 mm, it was considered
      abnormal, and in 12 cases was < 5 mm. Hysteroscopy detects the presence of 7
      atrophic endometrium, 19 polyps, 8 myomas, 4 cancer, 5 synechiae. Echography had
      a sensitivity of 90.9%, specificity of 72% and positive predictive value of
      90.9%. Hysteroscopy showed a sensitivity of 96.7%, a specificity of 92.8% and a
      positive predictive value of 96.8%. CONCLUSIONS: In conclusion we may suggest
      that TV scanning allows detection of endometrial pathology with a high
      sensitivity so it may be used as the first diagnostic step in the screening of
      postmenopausal women, but it should be completed by hysteroscopic evaluation when
      endometrial thickness is > 5 mm also in asymptomatic women in order to detect
      cancer in a early stage.

PMID- 9162882
TI  - [The need for urodynamic tests].
AB  - Two hundred forty women were studied, who underwent symptomatological anamnesis,
      clinical examination and urodynamic investigations for female urinary
      incontinence. Our aim was to distinguish among the three main forms of
      incontinence (stress, urge and mixed incontinence). When only symptomatological
      anamnesis is considered, there is an incidence of error in nearly a third of the
      cases and, when further factors like menopause, prolapse and parity are
      considered, the incidence of error does not reduce. A correct diagnosis can be
      determined only by a combined use of clinical assessment and urodynamic
      investigations. (As regards clinical examination, a positive stress test leads to
      a diagnosis of stress incontinence. As regards urodynamic investigations a
      cystometry positive for instability of the detrusor muscle leads to a diagnosis
      of urge incontinence. If both clinical examination and urodynamic investigations
      are positive, the diagnosis is of mixed incontinence.) Our findings suggest that
      routinely it is sufficient to execute only cystometry among urodynamic
      investigations.

PMID- 9162883
TI  - [The duration of the outpatient nonstress test (NST) and the diagnosis of fetal
      reactivity with noncomputerized cardiotocography, A critical review of 1160
      tracings].
AB  - STUDY DESIGN: Our purpose was to verify the times of appearance and the relative
      percentage of fetal reactivity during a nonstress test. The minimum time for each
      control has been fixed at 30 minutes. To identify fetal reactivity we have
      observed the conventional patterns of fetal heart rate. MATERIALS AND METHODS: We
      have examined 1160 cardiotocograms of 483 patients with obstetric low risk
      controlled by ambulatory NST in the morning and by appointment. We have divided
      the tracings according to three different periods of pregnancy (< 37, between 37
      and 40 and over 40 weeks) and each tracing in three periods of 10 minutes. In
      each period we have checked the mean values and standard deviations of
      accelerations, decelerations, uterine contractions and fetal movements. For each
      patient the total numbers of NST and the type of birth (spontaneous or caesarean
      section for fetal distress) has been considered. At statistic analysis we have
      employed "t"-Student test. RESULTS: We have observed a significative difference
      (p < 0.001) between the presence of fetal reactivity after 20 and 30 minutes and
      the number of doubtful cases after 30 minutes for the different periods of
      pregnancy. With minimum time of 30 minutes of NST, an incidence of doubtful cases
      of 4.48% and an incidence of caesarean section for fetal distress for the same
      group of 19.27% has been observed, while for all the cases with reactive NST this
      incidence intrapartum has been of 9.73%. CONCLUSION: Our experience confirms that
      the optimal duration of NST has been of 30 minutes. We think that this time must
      be suggested also from prudence, since the noncomputerized cardiotocography is
      often characterized by false positiveness and low predictability.

PMID- 9162884
TI  - [Lipoprotein(a) and the cardiovascular risk during estrogen-progestin replacement
      therapy in postmenopause].
AB  - A homogeneous group of 37 patients, aged between 52 and 61 years was considered
      in relationship to the metabolic response during hormonal replacement therapy
      (HRT). A free endocrinological-metabolic pathology control group, formed by 40
      patients, who were not treated with any therapy, was also considered. Study-trial
      was comprehensive of a 123 months follow-up, with some periods of study at 0, +6,
      +12 months. Metabolic responses of lipoprotein(a) and apolipoprotein A and B
      during the different follow-up steps were determined. Total and fractioned
      cholesterol and triglycerides were also determined. Significant correlations were
      shown between Lipo(a) and Apo B and also between Lipo(a) and LDL in both groups
      considered Lipoprotein(a) was determined by ELISA methodic and turbidimetric
      methodic. The aim of our study was to verify the importance of the new markers of
      the atheromatous risk. The reduction of lipoproteins middle value observed in the
      HRT group shows a little, but however present, estrogens action to the Lipo(a)
      itself. This fact testifies to the benefit of the use of HRT in post-menopause
      also as reg ards an evaluated cardiovascular risk inhibition.

PMID- 9162885
TI  - [The role of the pineal body in the endocrine control of puberty].
AB  - The pineal gland plays an important role in reproductive endocrinology. The
      epiphysis regulates seasonal variations in reproductive function of seasonally
      breeding animals. In humans, even if they are not seasonal breeders, the role of
      the pineal in reproductive endocrinology seems to be important as well. It
      appears to be of particular importance the endocrine control of the gland on
      pubertal sexual maturation. Even if not all researchers agree, several data
      suggest that elevated melatonin levels-characteristic of prepubertal age-keep the
      hypothalamic-pituitary-gonadal axis in quiescence: thus, an inhibitory effect on
      pubertal development is exerted. Subsequently, the decreasing serum melatonin
      with advancing age would result in activation of the hypothalamic pulsatile
      secretion of GnRH- and therefore of the reproductive axis-with consequent onset
      of pubertal phenomena. The production rate of melatonin does not change with age
      and no growth in pineal size from 1 to 15 years of age has been demonstrated by
      nuclear magnetic resonance (NMR) studies. Therefore the decrease of serum
      melatonin concentrations has been proposed to be due to the increase in body mass
      or, according to another hypothesis, to be also temporally linked to sexual
      maturation. Furthermore, recently, it has been suggested in rats that the pineal
      influences not only the pubertal sexual maturation, but even the gonadal and
      genital development and function of offspring, already during intrauterine life.
      Investigations are needed to evaluate this hypothesis in humans.

PMID- 9162886
TI  - [A rare cause of polyhydramnios: Steinert's syndrome. A clinical case report].
AB  - Steinert's syndrome is a systemic disease with autosome mother-to-child
      transmission, characterized by myotonia and muscular dystrophia. The syndrome's
      clinical characteristics include: respiratory and alimentation diseases, facial
      diplegia, generalized hypotonia, areflexia, atrophy, arthrogryposis, hydramnios,
      retard in psychomotor development, cataract and genital disorders. A case of
      pregnancy occurs in Steinert syndrome's patient with hydramnios as a predominant
      symptom, is presented. At birth, in the congenital neonatal form, there is grave,
      generalized hypotonia which causes a very quick death of the newborn. There are
      not many characters which can be found out by ultrasound: hydramnios, reduction
      of fetal tone and active movements, micrognathia. Consequently it is of the
      utmost importance in those cases an adequate prenatal genetic counseling and a
      correct obstetrical management.

PMID- 9162887
TI  - [Diffuse peritoneal leiomyomatosis. A clinical case report].
AB  - Leiomyomatosis peritonealis disseminata (LPD) is a rare condition characterized
      by numerous leiomyomas throughout the peritoneal cavity which appears grossly
      malignant but histologically benign. LPD occurs during reproductive age,
      especially the third and fourth decades. The etiology of the disorders is so far
      unknown, but presumedly hormonal. One case of LPD is presented and discussed. The
      patient, a 25-year-old nulliparous woman complained of aspecific colic type
      abdominal pain. Pelvic examination revealed a mass of about 4 x 5 cm occupying
      the cul de sac. Exploratory laparatomy revealed the mass and numerous nodules on
      the surface of the right ovary and of the omentum. After surgery no therapy was
      done and follow-up was done only by ultrasound. After 4 years follow-up the
      patient is well and is now pregnant at the XXV week of gestation. The number of
      cases of LPD documented in the literature to date is only about 50 cases, but
      they are likely to be much more, because of many asymptomatic cases. A
      conservative approach is recommended, but in the last years we have always had
      more reports of malignant degeneration (about 10%). So when surgical castration
      is not possible for age and or children desire, more aggressive follow-up should
      be recommended. In fact recidive is so far the most unfavourable prognostic
      factor.

PMID- 9162889
TI  - Advances in nephrology and dialysis. Proceedings of the 27th San Carlo Course.
      Milan, Italy, December 8-11, 1995.

PMID- 9162888
TI  - [Secretory IgA of the cervical mucus in neoplastic and nonneoplastic conditions
      of the uterine cervix].
AB  - In 39 women affected by cervical intraepithelial neoplasia (CIN) concentration of
      the cervical mucus secretory IgA (sIgA) was significantly higher than in 414
      controls matched for age, reproductive status and smoking habit (196 healthy
      women; 109 with "specific" and "aspecific" cervicitis or cervico-vaginitis; 51
      with benign epithelial disorders of the cervix; 40 with adenomatous cervical
      polyp and 18 with early invasive exocervical squamous carcinoma). CIN carried the
      highest proportion of cases with sIgA detectable or beyond the cut-off value and
      sIgA concentration was inversely related to CIN grade. Present data confirm our
      preliminary investigation on the cervical total IgA and explain that any
      increased levels of these IgA are induced by the secretory and not serum fraction
      of this immunoglobulin. We still don't know the exact meaning and value of the
      present results. It is only possible to suppose that they are the expression of a
      vigorous local immune activation adverse to CIN, which is elevated for as long as
      the architecture of cervical glandular epithelia is preserved.

PMID- 9162890
TI  - Selected medical malpractice cases in New Jersey.

PMID- 9162891
TI  - Proceedings of the 1st International Conference on East-West Perspectives on
      Functional Foods. Singapore, September 26-29, 1995.

PMID- 9162892
TI  - [Aortic dissection].
AB  - The aortic dissection is an expanding intramural hematoma in the aortic wall
      separating its layers. That is the most common catastrophic condition of the
      aorta. Its incidence in Hungary about 3.0%/000/year may be appreciated. The
      mortality rate of the untreated cases exceeds the 90 per cent. The dissection
      begins by an intimal tear or by a medial hemorrhage, seldom. The progressing
      hematoma results in a false lumen running parallel with the true aortic lumen. On
      the basis of the location of the primary intimal tear the dissection may be
      proximal or distal. The inherited or acquired medial weakness and the
      hypertension are the main etiologic factors. Some pathological findings refer to
      predisposing role of the atherosclerosis. The ischemia caused by the dissection
      may damage any organ. The clinical picture is characterized by the polymorphism
      and the migration of the clinical signs. The suspicion of the disease may be
      raised on the basis of the anamnesis and the clinical picture. The diagnosis may
      be confirmed by the rutin chest roentgenograms and by the angiography, CT, MRI
      and ultrasonic examinations. The transoesophageal echocardiography is the best
      diagnostic tool. The treatment is medical and/or surgical. Advances in the
      surgical treatment brought turn in the very poor prognosis.

PMID- 9162893
TI  - [Lawn grass (Poaceae) causing hayfever in the South Plain of Hungary. Results of
      aeropalinologic and allergologic studies 1989-95].
AB  - The importance of Grass (Poaceae) pollen as a cause of hay fever in the South
      Plain of Hungary was studied by aeropalinological and allergological methods.
      Since 1989 the pollen counting has been performed with the help of a Lanzoni VPPS
      2000 sampler. On the basis of the pollen counting the second most important
      allergen pollen of this region are the grass pollen. From 1989 to 1995 skin prick
      tests (Soluprick, Epipharm) were performed in 642 patients with seasonal allergic
      rhinitis. 261 of these patients suffer from hay fever in May and June when the
      daily pollen count of grass pollen is the highest. The skin prick tests of these
      261 patients were positive to Poaceae in 84%, and to Secale in 63%. But 57% of
      the patients was allergic to both Poaceae and Secale, so the exact allergen
      research is very important before hyposensitisation. Ragweed (63%) and Mugwort
      (33%) sensitivity was found also in high percent of the grasspollinosis patients
      with symptoms during the late summer season too.

PMID- 9162894
TI  - [Cefaclor therapy followed by serum sickness-like symptoms].
AB  - Cefaclor is an oral cefalosporin for a wide range of gram-positive and gram
      negative infection. A retrospective study of cefaclor toxicoderma cases at the
      Department of Dermatology of Heim Pal Children's Hospital found 11 cases. After
      the administration of the drug, serum sickness like syndromes were observed. The
      characteristic symptoms were: erythema multiforme like urticaria, polyarticular
      swelling and oedema of joints and fever. Laboratory findings were: arised
      activity of the liver enzymes. After the acute symptoms urticaria factitia
      appeared.

PMID- 9162895
TI  - [Leukocyte migration during erythrocyte sedimentation].
AB  - Sedimentation properties of leukocytes was measured with a new, simple and
      reproducible method. The increment of leukocyte concentration was determined in
      the upper 100 mm section of the sedimentation blood column after one hour gravity
      sedimentation of the whole blood. The result (leukocyte antisedimentation rate,
      LAR) was expressed in percentage of the original, presedimentation leukocyte
      concentration. Blood samples taken from 35 healthy adults were investigated and
      12.5% and 17.4% increments were found in total leukocyte count and in granulocyte
      concentration respectively in the upper half of the sedimentation blood column.
      The mean coefficient of variation of LAR measurements was 3.2% LAR was found
      significantly higher in a mixed group of patients than in healthy controls. The
      sedimentation properties of leukocytes were in significant correlation with
      leukocyte adherence (p < 0.01), with whole blood viscosity, hematocrit, and
      erythrocyte sedimentation rate (each p < 0.05) when blood samples of healthy
      individuals and postoperative intensive care patients were analysed in
      combination. In vitro pre-treatment of patients' blood samples with prednisolone
      and lidocaine resulted in a significant diminishment of LAR in a concentration
      dependent manner.

PMID- 9162896
TI  - [Adrenoleukodystrophy].
AB  - 7-year-old boy with adrenoleukodystrophy is presented with the typical clinical
      picture, biochemical findings and review of the literature. The obligate carrier
      status of the mother and the asymptomatic adrenoleukodystrophy of the 5-year-old
      brother are biochemically proved. Therapeutic regime of Lorenzo's oil has been
      introduced to the young brother, and the question of bone marrow transplantation
      is discussed.

PMID- 9162897
TI  - [Medical education at the School of Medicine of the Erzsebet University of Pecs
      in the years 1924-1944, as well as some current problems].

PMID- 9162898
TI  - [Istvan Szam, M.D., would be 70 years old this year].

PMID- 9162899
TI  - Noonan syndrome associated with neuroblastoma: a case report.
AB  - We report a case of a child with Noonan phenotype and incidental radiographic
      findings of mediastinal neuroblastoma. Recent studies have reported an increased
      association of Noonan syndrome with some malignancies, and the case we present
      here is the first reported case to our knowledge of an association of
      neuroblastoma with Noonan syndrome.

PMID- 9162900
TI  - c-Myc/Max heterodimers bind cooperatively to the E-box sequences located in the
      first intron of the rat ornithine decarboxylase (ODC) gene.
AB  - The oncoprotein c-Myc plays an important role in cell proliferation,
      transformation, inhibition of differentiation and apoptosis. These functions most
      likely result from the transcription factor activity of c-Myc. As a heterodimer
      with Max, the c-Myc protein binds to the E-box sequence (CACGTG), which is also
      recognized by USF dimers. In order to test differences in target gene recognition
      of c-Myc/Max, Max and USF dimers, we compared the DNA binding characteristics of
      these proteins in vitro using vaccinia viruses expressing full-length c-Myc and
      Max proteins. As expected, purified c-Myc/max binds specifically to a consensus E
      box. The optimal conditions for DNA binding by either c-Myc/Max, Max or USF
      dimers differ with respect to ionic strength and Mg2+ ion concentration. Most
      interestingly, the c-Myc/Max complex binds with a high affinity to its natural
      target, the rat ODC gene, which contains two adjacent, consensus E-boxes. High
      affinity binding results from teh ability of c-Myc/Max dimers to bind
      cooperatively to these E-boxes. We propose that differential cooperative binding
      by E-box binding transcription factors could contribute to target gene
      specificity.

PMID- 9162901
TI  - Structure of a bis-amidinium derivative of hoechst 33258 complexed to
      dodecanucleotide d(CGCGAATTCGCG)2: the role of hydrogen bonding in minor groove
      drug-DNA recognition.
AB  - The crystal structure is reported of a complex between the dodecanucleotide
      sequence d(CGCGAATTCGCG)2and an analogue of the DNA binding drug Hoechst 33258,
      in which the piperazine ring has been replaced by an amidinium group and the
      phenol ring by a phenylamidinium group. The structure has been refined to an R
      factor of 19.5% at 2.2 A resolution. The drug is held in the minor groove by five
      strong hydrogen bonds, together with bridging water molecules at both ends. There
      are few other contacts with the floor of the groove, indicating a lack of
      isohelicity with the groove and suggesting (i) that the observed high DNA
      affinity of this drug is primarily due to the array of hydrogen bonds and (ii)
      that these more than compensate for its poor isohelicity.

PMID- 9162902
TI  - Rapid selection of aminoacyl-tRNAs based on biotinylation of alpha-NH2 group of
      charged amino acids.
AB  - A rapid selection procedure to separate low amounts of aminoacylated tRNAs from
      large pools of inactive variants is described. The procedure involves a three
      step protocol. After initial aminoacylation of a tRNA pool, N-hydroxysuccinimide
      ester chemistry is applied to biotinylate the alpha-NH2 group of the amino acid
      bound to the 3'-end of a tRNA. The biotin tag is used to capture the derivatized
      tRNAs on streptavidin-conjugated magnetic beads. Variants bound to the solid
      phase can be amplified by RT-PCR and transcription, providing tRNAs for
      subsequent selection rounds.

PMID- 9162903
TI  - 19 ORFs and putative genes on the 81 kb contig of Arabidopsis thaliana chromosome
      III.

PMID- 9162904
TI  - [Quantitative salivary gland scintigraphy--a recommended examination prior to and
      after radioiodine therapy].
AB  - AIM: The aim of this study was to evaluate possible deterioration of salivary
      gland function due to radioiodine therapy with low activities using standardized
      quantitative salivary gland scintigraphy (qSZ). In addition, the prevalence of
      sialopathies was estimated in patients with thyroid dysfunction. METHODS: Prior
      to routine thyroid scintigraphy qSZ was performed after i.v. injection of 36-126
      MBq 99mTc-pertechnetate, and both uptake and excretion fraction were calculated
      as a measure of parenchymal function and saliva excretion, respectively 312
      healthy patients served as reference for a normal data base. 144 patients
      underwent qSZ prior to and 3 months after radioiodine therapy. Results of qSZ in
      another 674 thyroid patients were evaluated for determining the prevalence of
      salivary gland dysfunction. RESULTS: Normal uptake was 0.45 +/- 0.14% and 0.39 +/
      0.12%, and normal excretion fraction amounted to 49.5 +/- 10.6% and 39.1 +/-
      9.2% in parotid and submandibular glands, respectively. Despite salivary gland
      stimulation with ascorbic acid during radioiodine therapy a significant activity
      related functional impairment of 14-90% could be measured after application of
      0.4-24 GBq of 131I. Prevalence of pretreatment sialopathies was 77/674 = 11.4% in
      single glands, and there was a global salivary gland functional impairment in
      52/674 = 7.7%. CONCLUSION: Together with thyroid scintigraphy qSZ is an easy to
      perform examination without additional radiation burden. It can be recommended in
      all patients prior to and after radioiodine therapy both in order to quantify and
      to document possible parenchymal impairment induced even by low activities of
      131I.

PMID- 9162905
TI  - [Radioiodine therapy of small, solitary autonomous adenomas].
AB  - AIM: In most cases of unifocal autonomous adenomas the indication of radioiodine
      therapy has so far been given only if the volume of the adenomas is > 8 ml, or if
      the Tc-Uptake is > 2% in combination with suppressed TSH incretion. We have
      investigated the question how far the indication of radioiodine therapy should be
      extended to other cases. METHODS: Between March 1993 and April 1994 we treated 11
      patients who did not fulfil these criteria but suffered from thyreogenic
      complaints. RESULTS: After the radioiodine therapy, all the 11 patients improved
      evidently. CONCLUSION: We suggest extending the indication of radioiodine therapy
      in order also to treat small unifocal adenomas.

PMID- 9162906
TI  - [Impact of pretreatment variables on the outcome of standardized 131I therapy
      with 150 Gray in Graves' disease].
AB  - AIM: We examined the impact of several pretreatment variables on thyroid size and
      function in 61 patients with Graves' disease one year after a standardized [131]I
      treatment with 150 Gray. METHODS: FT3, FT4, and TSH serum concentrations were
      determined before and 1.5, 3, 6, and 12 months after therapy. Thyroid size was
      measured by ultrasound and scintigraphy before and one year after therapy.
      RESULTS: One year after therapy, 30% of the patients had latent or manifest
      hyperthyroidism, 24% were euthyroid, and 46% had developed latent or manifest
      hypothyroidism. Age and initial thyroid volume were major predictors of post
      therapeutical thyroid function. Thus, persistent hyperthyroidism was observed in
      70% of the patients age 50 years and older with a thyroid size of more than 50
      ml. With few exception, thyroid size markedly decreased after therapy. Initial
      thyroid size and age were also major predictors of posttherapeutical thyroid
      volume. Thyroid size normalized in all patients younger than 50 years of age,
      independent from initial thyroid size. CONCLUSION: Radioiodine treatment with 150
      Gray causes a considerable decrease in thyroid size in most patients with Graves'
      disease. Age and initial thyroid volume are important determinants of thyroid
      function and size after therapy and should be considered in dose calculation.

PMID- 9162907
TI  - [Effect of antithyroid medication on the effective half-life and uptake of 131
      iodine following radioiodine therapy].
AB  - AIM: A radioiodine therapy (RIT) in thyrotoxic patients receiving antithyroid
      drugs (ATD) leads in comparison to nonpretreated patients either to higher
      therapeutic doses or to higher treatment failure rates. Aim of this study was to
      optimize the effect of RIT in patients pretreated with ATD. METHODS: Therefore,
      the influence of ATD was assessed in 109 patients with shortened effective half
      life of 131I. RIT was performed under stationary conditions. Radioiodine activity
      of the thyroid gland was measured twice a day. In 77 patients antithyroid
      medication was stopped three days after RIT. The progress of the first RIT and of
      a second radioiodine application, which still was necessary in 29 patients, was
      compared to 32 patients receiving ATD, continuously. RESULTS: Values of effective
      half-life for 131I rose significantly from 3.2 +/- 0.2 to 5.7 +/- 0.2 days
      (Graves' disease: 3.4 to 5.7 days; toxic goiters' disease: multifocal autonomy
      3.2 to 6.2 days; unifocal autonomy 2.5 auf 5.0 days) 2-3 days after stopping ATD.
      There was an increase of the 131I-uptake of a second after stopping ATD, too. In
      contrast, 131I-uptake of a second RIT decreased significantly in patients
      receiving ATD, continuously. CONCLUSION: Effective half-life and uptake of 131I
      was affected significantly by ATD. The stop taking of ATD after RIT is useful to
      improve an apparent insufficient RIT in thyrotoxic patients receiving ATD.

PMID- 9162908
TI  - [Low-risk thyroid carcinoma--therapy, follow-up and prognosis].
AB  - AIM AND METHODS: A retrospective study was performed to determine the frequency
      of local recurrences and distant metastases as well as potential risk factors in
      patients with low-risk differentiated thyroid carcinoma. In addition, the
      efficiency of our follow-up programme and the diagnostic value of the procedures
      administered was to be evaluated. RESULTS: 41/740 (8%) patients developed 62
      recurrences at a mean 4.7 years after the onset of the disease. In 14 cases the
      tumor marker thyroglobulin was the first diagnostic sign. 13 recurrences were
      diagnosed by chest x-ray and/or CT. In 12 cases recurrences/metastases were
      detected by iodine-131 whole body scan, and 8 cases by ultrasound of the neck. A
      good prognosis was found if patients were under 45 years of age when the tumor
      was first diagnosed, and if the tumor did not exceed 20 mm in diameter. The
      prognosis was not statistically significant influenced by histology, gender and
      surgical methods. The 10-year survival rate for papillary carcinomas was 91% and
      for follicular carcinomas 84%. CONCLUSIONS: We recommend yearly follow-up
      examinations with selective use of other diagnostic methods in order to provide
      best patient care.

PMID- 9162909
TI  - [The first results of the international project "Tuberculosis in the Tomsk
      region"].

PMID- 9162910
TI  - [The epidemiologic situation of tuberculosis in West Siberia in 1991-1995].
AB  - Analyzing the major tuberculosis epidemiological indices in West Siberia in 1991
      1995 has indicated that the epidemic situation in the region tends to
      catastrophically deteriorate. Its general morbidity doubled, amounting to 83.5
      per 100,000 inhabitants. Among children, there was a rise in morbidity rates from
      18.5 per 100,000 in 1993 ot 21.3 in 1995. This index was 33.1% for children aged
      0 to 4 years. Morbidity in adolescents increased by 30.2%. Deaths from
      tuberculosis and its sequelae showed a 1.7-fold increase, accounting for 16.0 per
      100,000 inhabitants. During the first year, the deceased increased in number from
      9.1% in 1991 to 17.3% in 1996.

PMID- 9162911
TI  - [The tuberculosis situation and urgent task to optimize antitubercular care for
      the population in the Ural and Volgo-Viatka regions].
AB  - The tuberculosis epidemiological situation in the Ural and Volgo-Vyatka regions
      is recognized to be extraordinary. There is a reduction in the rate of mortality
      growth in some areas. A dispersion criterion for epidemiological indices is
      proposed to evaluate the control and management of the tuberculosis situation. To
      improve the quality of antituberculosis care, the authors propose urgent measures
      in the near future, which are to be financially supported at most.

PMID- 9162912
TI  - [Current socioepidemiologic and clinico-pathogenetic aspects of pulmonary
      tuberculosis in the Republic of Moldova].
AB  - Among the first detected patients, there was a reduction in the proportion of
      subjects with posttuberculous changes in the lung decreases in the presence of
      the deteriorating epidemiological situation. Risk factors of social diseases are
      of much importance in the development of tuberculosis at present. Infiltrative
      processes with lung tissue destruction and bronchogenic dissemination are
      essential in the clinical pattern of the disease. Exogenous infection and
      superinfection play an important role in the pathogenesis of tuberculosis. For
      most patients with tuberculosis without residual changes in the lung, the optimum
      hospital stay is 6 months and the total duration of a basic treatment regimen is
      1-1.5 year. To reduce the time of treatment in patients with tuberculosis
      developed in the presence of residual changes in the lung is now inadvisable.

PMID- 9162913
TI  - [Aleksandr Grigor'evich Khomenko (To his 70-th birthday)].

PMID- 9162914
TI  - [The epidemiology of tuberculosis and organization of its control in Uzbekistan].
AB  - The epidemic situation associated with tuberculosis has tended recently to
      aggravate in Uzbekistan, in the Aral region, arid and rural areas in particular.
      The pattern of detected tuberculosis has become worse. The reasons for
      epidemiological troubles and deteriorated organized antituberculosis work in the
      republic are clarified in the paper. A governmental programme for tuberculous
      prevention and morbidity reduction with antituberculous measures being financed
      has been prepared, which determines immediate tuberculosis control strategy.
      Stepwise implementation of this programme will prevent the further spread of this
      infection and enhance the efficiency of tuberculosis treatment.

PMID- 9162915
TI  - [Epidemiologic situation of tuberculosis in Armenia under the present condition].
AB  - The epidemiological situation in Armenia is very grave: the tuberculosis cases
      registered in 1994 are 19.6 per 100,000 inhabitants, this is 16.6% higher than
      the figure in 1993. Mortality rates in 1994 are 3.1 per 100,000 persons.
      Morbidity in males is 2.5 times higher than that in females. The greatest
      proportion of the first cases detected is in the age group of 25-34 years.
      Infiltrative tuberculosis with multiple decay and its acute course is prevalent
      in the pattern of tuberculosis morbidity. Activities in prophylactic measures
      drastically has declined due to power crisis and grave socioeconomic conditions
      of the republic. Groups of migrants as potential carriers of undiagnosed
      tuberculosis forms are gaining a great significance among patients with
      tuberculosis.

PMID- 9162916
TI  - [Epidemiologic situation of tuberculosis in the Republic of Kazakhstan].
AB  - The tuberculosis epidemiological situation has greatly deteriorated in the
      Republic of Kazakhstan in recent years. Tuberculosis morbidity has annually
      increased by 11.1% and, but in 1995 it amounted to as much as 100 per 100,000 in
      some areas and mortality was 29.5%. Forty five thousand patients with active
      tuberculosis types are registered at tuberculosis dispensaries, among them 12
      thousand patients isolate Mycobacterium tuberculosis. The main reason is sharply
      deteriorated socioeconomical conditions and lower volumes of antituberculous
      measures.

PMID- 9162917
TI  - [The impact of ecological pressing on tuberculosis and nonspecific lung diseases
      in the Astrakhan' region].
AB  - The correlation analysis was used to examine the epidemiological indices of the
      morbidity of tuberculosis, pneumonia, chronic bronchitis, bronchial asthma, and
      lung cancer in the Astrakhan region in 1987-1994. The indices were compared with
      each other and with varying air, water, and soil levels of toxicants. The
      magnitude of the effects of pollutants on the incidence of respiratory diseases
      ranged from 61% (for tuberculosis) to 93.3% (for pneumonia). The effects of the
      water and soil concentrations of toxicants proved to be less insignificant, by
      varying from 28.7% in tuberculosis to 4.8% in lung cancer. The effects of
      toxicant levels on tuberculosis morbidity are 5 times less than those during
      fibrous-cavernous processes and twice less than in first detected tuberculosis at
      the stage of decay with bacterial isolation. The pollutants containing sulfur
      were found to adversely affect mainly patients with tuberculosis or lung cancer.
      The study makes it necessary to consider patients with the aforesaid diseases as
      the objects of ecological pressing that directly has impact on the course of
      diseases and their outcomes.

PMID- 9162918
TI  - [Tuberculosis control in the Kaliningrad region].
AB  - Since 1992, there has been a rise in tuberculosis mortality and morbidity among
      adults and children in the Kaliningrad region. By 1995, tuberculosis morbidity
      and mortality have increased by 88 and 92%, respectively. Mortality among
      children has shown a 2.2-fold increases. The pattern of clinical pulmonary
      tuberculosis types has become worse.

PMID- 9162919
TI  - [Epidemiology of tuberculosis in the Amur region].
AB  - Since 1991, the tuberculosis epidemiological situation has become worse: its
      morbidity has increased from 36.4 in 1990 to 60.6 in 1994 and mortality has grown
      from 5.3 in 1990 to 11.3 in 1994 and 22.2 in 1995 per 100,000. There has been a
      rise in destructive and fibrous-and-cavernous tuberculoses in the pattern of
      morbidity. The efficiency of treatment has drastically decreased. The basic
      principles in the deterioration of the epidemiological situation are
      socioeconomic conditions, inadequate financing of antituberculous measures.

PMID- 9162920
TI  - [The impact of migratory processes on the epidemiology of tuberculosis in the
      Stavropol' territory].
AB  - Tuberculosis morbidity in the Stavropol territory has recently increased from
      31.5 to 43.0 per 100,000. It is particularly high among migrants: 499.0 per
      100,000 migrants in 1995. There are high incidence rates of tuberculosis and the
      migrants from Chechnya were shown to adversely affect the epidemiology of
      tuberculosis in the Stavropol territory, on the contamination processes in the
      native children in particular.

PMID- 9162921
TI  - [Thanatogenesis of respiratory tuberculosis under the present conditions].
AB  - Autoptic findings of 120 patients with respiratory tuberculosis indicate that
      under the present-day conditions, the prevalent cause of death was a progressive
      tuberculous process as caseous pneumonia (89% of cases), which is much higher
      than our previous findings (42.9% in 1989 versus 66.% in 1994). Caseous pneumonia
      chiefly resulted from fibrous-cavernous tuberculosis, less frequently from an
      independent entity or manifestations of disseminated tuberculosis. Fibrous
      cavernous tuberculosis, the major clinical form in the deceased, was frequently
      associated with specific involvement of intrathoracic lymph nodes (10.8% of
      cases) and also complicated by the hematogenic generalization of the process
      (6.7%) and specific pericarditis (5.0%). Progressive tuberculosis resulted in its
      later detection in a third of cases and irregular treatment in two thirds.

PMID- 9162922
TI  - [Acute miliary tuberculosis].
AB  - The clinical picture of acute miliary tuberculosis is characterized in 120
      patients followed up by the author in 1975-1996. The patients' age varied from 17
      to 62 years. Variants of clinical forms of miliary tuberculosis, specific
      features of the course tuberculous meningoencephalitis in miliary tuberculosis
      are given. In the past 3 years, the clinical picture of the disease has
      aggravated and its extremely severe malignant forms appeared.

PMID- 9162923
TI  - [Current trends in the epidemiology of tuberculosis and ways of reducing a
      reservoir of infection].

PMID- 9162924
TI  - [Treatment and outcomes of disseminated pulmonary tuberculosis].
AB  - The efficiency of treating 163 patients with first detected disseminated
      pulmonary tuberculosis in the past 30 years is analyzed. The efficiency of
      antibacterial therapy has been reducing with each decade owing to the detection
      of advanced diseases with multiple destructive changes, patient incompliance due
      to alcoholism, rare uses of intravenous and inhalation route of administering
      antituberculous drugs.

PMID- 9162925
TI  - [Effectiveness of complex treatment in combination with short-wave therapy and
      protease inhibitors in first detected patients with pulmonary tuberculosis].
AB  - Combined drug therapy ceases bacterial isolation and clinical symptoms of the
      disease and resolves infiltration in most patients after 1-month therapy. Gordox
      has a pronounced inhibitory action on Mycobacterium tuberculosis irrespective of
      their responses to antibiotics. L-transformation of M. tuberculosis was found
      with 5000-10,000 ATpE (U) of gordox.

PMID- 9162926
TI  - [Specific features of the pattern and clinical manifestations of respiratory
      tuberculosis in new cases under the present-day conditions].
AB  - The study of clinical and X-ray manifestations of the disease in 270 patients has
      shown that the incidence of disseminated tuberculosis with its acute onset and
      marked clinical manifestations has greatly increased. It is difficult to make a
      diagnosis of recently more frequent tuberculosis of the intrathoracic lymph nodes
      in adults due to acute clinical manifestations resulting from nonspecific
      inflammation with frequent abscessing at the site of atelectasis in lobar and
      segmental bronchopulmonary lesions, due to late detection of meagre bacterial
      isolation, to frequent involvement sites in 3, 4, and 5 segments. Acute
      generalized disseminated tuberculosis generally follows obscure clinical
      manifestations from extrapulmonary inflammation in 2-4 months. Acute miliary
      tuberculosis has frequently accompanied by bacterial isolation and frequently
      destructions.

PMID- 9162927
TI  - [Course of a specific process in high risk ecological areas].
AB  - In the past 5 years, the epidemiological situation associated with tuberculosis
      has greatly aggravated in the high ecological risk areas (the towns of Engels and
      Volsk) of the Saratov region. Morbidity has increased from 40 to 48 per 100,000
      persons (to 79 in Engles). The proportion of destructive and acutely progressive
      types of pulmonary tuberculosis and the number of those died from tuberculosis
      among the followed up at the tuberculosis dispensary are on the increase.

PMID- 9162928
TI  - [Clinical and X-ray characteristics of tuberculosis in adults and children and
      reasons for its late detection].
AB  - The authors' findings suggest that the clinical pattern of tuberculosis morbidity
      in adults and children has recently become worse. Severe caseous pneumonia with
      its acute onset and malignant course by the type of galloping consumption with
      massive bacterial isolation and deaths in 42.8% of cases was analyzed. The
      complicated course mainly of the primary tuberculosis complex (40.8%) and
      tuberculosis of the intrathoracic lymph nodes was seen in 25% of ill children.
      Tuberculous meningitis was diagnosed in 20% of cases in the morbidity pattern of
      extrapulmonary tuberculosis. The reasons for late detection of disease are the
      poor organization of prophylactic fluorographic examinations of the adult
      population, tuberculin diagnosis, vaccination, revaccination of BCG and
      chemoprophylaxis in children at risk. The authors note unawareness of
      tuberculosis among the adult population, which was found through questionnaires.

PMID- 9162929
TI  - [New aspects in pathogenesis of respiratory sarcoidosis].
AB  - A comprehensive examination was made of 101 patients with sarcoidosis of the
      intrathoracic lymph nodes (ITLN) (n = 33), with that of ITLN and lung (n = 47) or
      sarcoidosis of the lung (n = 21). Special studies were conducted to examine the
      pulmonary scintigraphic and X-ray pneumopolygraphic findings reflecting impaired
      microcirculation and biomechanics of respiration, the levels of medium-weight
      molecules, their fractions, and small-weight molecules in the sera and urine,
      which reflects the severity of endoxemia, as well as the electrophoretic motility
      of red blood cells which are involved in metabolism and the degree of tissue
      hypoxia. The findings have confirmed that there are respiratory, circulatory, and
      tissue hypoxias, and endogenous intoxication just in earliest respiratory
      sarcoidosis, which is of definite importance in the pathogenesis of the disease,
      allowing the use of pathogenetic agents as antihypoxants to be justified.

PMID- 9162930
TI  - [Bactericidal effects of maxaquin on mycobacterium tuberculosis].
AB  - Maxaquine is a fluoroquinolone agent that is effective against Mycobacterium
      tuberculosis (MBT). The drug was tested for effects on MBT growth in the infected
      lung tissue in relation to its concentration and exposure time. The bactericidal
      effect was found to be achieved no earlier than 72 hours of its administration.
      The minimum bactericidal concentration of maxaquine was 2 micrograms/ml.

PMID- 9162931
TI  - [Liver morphology in patients with pulmonary tuberculosis with viral hepatitis B
      and organochlorine pesticides markers].
AB  - The paper presents the results of life liver biopsy in 34 patients with pulmonary
      tuberculosis whose blood samples displayed viral hepatitis B markers (n = 18,
      Group 1) and organochlorine pesticides (n = 16, Group 2). Hepatic biopsy
      specimens were examined, by using histological, histochemical, and electron
      microscopic techniques. The entities of hepatic lesions identified were virtually
      identical in the comparable groups.

PMID- 9162932
TI  - [Action of dissolved ozone on mycobacterium tuberculosis and alveolar macrophages
      in experimental tuberculosis].
AB  - Sixty CBA mice were intravenously inoculated with the Mycobacterium tuberculosis
      (MBT) strains Erdman and 2255 (a polyresistant clinical strain) pretreated with
      dissolved ozone (experimental groups), a single therapeutical dose. of dissolved
      ozone being intravenously injected. By 1 month of inoculation, all control mice
      (MBT-inoculated and ozone-untreated) died and in their organs there were a great
      deal of MBT both outside and inside the macrophages. No pathogen in its typical
      form was not found in experimental mice, but there were many granular and L
      forms, the lung showing a large number of highly vacuolized (foamy) alveolar
      macrophages (AM). All experimental mice survived by month 5 and their organ
      examination showed that the pathogen was detectable only inside the macrophages,
      but they are chiefly unchanged (more elongated and badly stained with aniline
      dyes). Juvenile forms are prevalent among AM. It should be concluded that the
      action of dissolved ozone on AM and MBT is heterodirectional.

PMID- 9162933
TI  - [Antitubercular vaccination of children in the Irkutsk region: the status and
      prospects].

PMID- 9162934
TI  - [A concept of control of antituberculous measures under new socioeconomic
      conditions in Russia].

PMID- 9162935
TI  - [Age and sex related structure of first detected patients with tuberculosis in
      Dagestan].

PMID- 9162936
TI  - [Dynamics in tuberculosis morbidity in the Orenburg region in 1980-1995].

PMID- 9162937
TI  - [Improving antitubercular care for children under the conditions of the tense
      social and epidemiological situation in the country].

PMID- 9162938
TI  - [Prevention of bronchitis in workers of the integrated asbestos mining-enriching
      works].

PMID- 9162939
TI  - [Scientific session of the Ural Research Institute of Tuberculosis, Department of
      Health and Medical Industry of the Russian Federation and the working Meeting of
      Phthisiologists of the Ural and Volgo-Viatka regions].

PMID- 9162941
TI  - For Guldberg and Waage, with love and cratic entropy.

PMID- 9162940
TI  - [Trends in tuberculosis epidemiology in the Ivanovo Region and its stabilizing
      measures].
AB  - In 1993-1995, tuberculosis morbidity increased from 37.8 per 100,000 inhabitants
      to 55.7. The increase was due chiefly due to incidence rates among urban
      dwellers. In the same period, tuberculosis mortality rose from 10.2 to 55.7 per
      100,000. Tuberculosis control strategy has been revised under the conditions of
      the increasing spread of tuberculosis infections and the Central Research
      Institute of the Russian Academy of Medical Sciences jointly with the WHO Global
      Programme Department has developed the programme "Detection of Patients Isolating
      Mycobacterium tuberculosis by the ??Tsil-Nilsen method and Their Short-Term
      Chemotherapy". Analyzing the preliminary data available during 2 quarters
      (Quarter IV, 1995, and Quarter I, 1996) indicated its adequate efficiency.

PMID- 9162942
TI  - Molecular collapse: the rate-limiting step in two-state cytochrome c folding.
AB  - Experiments with cytochrome c (cyt c) show that an initial folding event,
      molecular collapse, is not an energetically downhill continuum as commonly
      presumed but represents a large-scale, time-consuming, cooperative barrier
      crossing process. In the absence of later misfold-reorganization barriers, the
      early collapse barrier limits cyt c folding to a time scale of milliseconds. The
      collapse process itself appears to be limited by an uphill search for some
      coarsely determined transition state structure that can nucleate subsequent
      energetically downhill folding events. An earlier "burst phase" event at strongly
      native conditions appears to be a non-specific response of the unfolded chain to
      reduced denaturant concentration. The molecular collapse process may or may not
      require the co-formation of the amino- and carboxyl-terminal helices, which are
      present in an initial metastable intermediate directly following the rate
      limiting collapse. After the collapse-nucleation event, folding can proceed
      rapidly in an apparent two-state manner, probably by way of a predetermined
      sequence of metastable intermediates that leads to the native protein structure
      (Bai et al., Science 269:192-197, 1995).

PMID- 9162943
TI  - The role of helix formation in the folding of a fully alpha-helical coiled coil.
AB  - To determine when secondary structure forms as two chains coalesce to form an
      alpha-helical dimer, the folding rates of variants of the coiled coil region of
      GCN4 were compared. Residues at non-perturbing positions along the exterior
      length of the helices were substituted one at a time with alanine and glycine to
      vary helix propensity and therefore dimer stability. For all variants, the
      bimolecular folding rate remains largely unchanged; the unfolding rate changes to
      largely account for the change in stability. Thus, contrary to most folding
      models, widespread helix is not yet formed at the rate-limiting step in the
      folding pathway. The high-energy transition state is a collapsed form that
      contains little if any secondary structure, as suggested for the globular protein
      cytochrome c (Sosnick et al., Proteins 24: 413-426, 1996).

PMID- 9162944
TI  - Hydrophilicity of cavities in proteins.
AB  - Water molecules inside cavities in proteins constitute integral parts of the
      structure. We have sought a quantitative measure of the hydrophilicity of the
      cavities by calculating energies and free energies of introducing a water
      molecule into these cavities. A threshold value of the water-protein interaction
      energy at -12 kcal/mol was found to be able to distinguish hydrated from empty
      cavities. It follows that buried waters have entropy comparable to that of liquid
      water or ice. A simple consistent picture of the energetics of the buried waters
      provided by this study enabled us to address the reliability of buried waters
      assigned in experiments.

PMID- 9162945
TI  - Patterns in ionizable side chain interactions in protein structures.
AB  - In a selected set of 44 high-resolution, non-homologous protein structures, the
      intramolecular hydrogen bonds or salt bridges formed by ionizable amino acid side
      chains were identified and analyzed. The analysis was based on the investigation
      of several properties of the involved residues such as their solvent exposure,
      their belonging to a certain secondary structural element, and their position
      relative to the N- and C-termini of their respective structural element. It was
      observed that two-thirds of the interactions made by basic or acidic side chains
      are hydrogen bonds to polar uncharged groups. In particular, the majority (78%)
      of the hydrogen bonds between ionizable side chains and main chain polar groups
      (sch:mch bonds) involved at least one buried atom, and in 42% of the cases both
      interacting atoms were buried. In alpha-helices, the sch:mch bonds observed in
      the proximity of the C- and N-termini show a clear preference for acidic and
      basic side chains, respectively. This appears to be due to the partial charges of
      peptide group atoms at the termini of alpha-helices, which establish
      energetically favorable electrostatic interactions with side chain carrying
      opposite charge, at distances even greater than 4.5 angstrom. The sch:mch
      interactions involving ionizable side chains that belong either to beta-strands
      or to the central part of alpha-helices are based almost exclusively on basic
      residues. This results from the presence of main chain carbonyl oxygen atoms in
      the protein core which have unsatisfied hydrogen bonding capabilities.

PMID- 9162946
TI  - Molecular dynamics simulations of N-terminal peptides from a nucleotide binding
      protein.
AB  - Molecular dynamics (MD) simulations of N-terminal peptides from lactate
      dehydrogenase (LDH) with increasing length and individual secondary structure
      elements were used to study their stability in relation to folding. Ten
      simulations of 1-2 ns of different peptides in water starting from the
      coordinates of the crystal structure were performed. The stability of the
      peptides was compared qualitatively by analyzing the root mean square deviation
      (RMSD) from the crystal structure, radius of gyration, secondary and tertiary
      structure, and solvent accessible surface area. In agreement with earlier MD
      studies, relatively short (< 15 amino acids) peptides containing individual
      secondary structure elements were generally found to be unstable; the hydrophobic
      alpha 1-helix of the nucleotide binding fold displayed a significantly higher
      stability, however. Our simulations further showed that the first beta alpha beta
      supersecondary unit of the characteristic dinucleotide binding fold (Rossmann
      fold) of LDH is somewhat more stable than other units of similar length and that
      the alpha 2-helix, which unfolds by itself, is stabilized by binding to this
      unit. This finding suggests that the first beta alpha beta unit could function as
      an N-terminal folding nucleus, upon which the remainder of the polypeptide chain
      can be assembled. Indeed, simulations with longer units (beta-alpha-beta-alpha
      and beta-alpha-beta-alpha beta-beta) showed that all structural elements of these
      units are rather stable. The outcome of our studies is in line with suggestions
      that folding of the N-terminal portion of LDH in vivo can be a cotranslational
      process that takes place during the ribosomal peptide synthesis.

PMID- 9162947
TI  - Phylogenetic occurrence of coiled coil proteins: implications for tissue
      structure in metazoa via a coiled coil tissue matrix.
AB  - We examined GenBank sequence files with a heptad repeat analysis program to
      assess the phylogenetic occurrence of coiled coil proteins, how heptad repeat
      domains are organized within them, and what structural/functional categories they
      comprise. Of 102,007 proteins analyzed, 5.95% (6,074) contained coiled coil
      domains; 1.26% (1,289) contained "extended" (> 75 amino acid) domains. While the
      frequency of proteins containing coiled coils was surprisingly constant among all
      biota, extended coiled coil proteins were fourfold more frequent in the animal
      kingdom and may reflect early events in the divergence of plants and animals.
      Structure/function categories of extended coils also revealed phylogenetic
      differences. In pathogens and parasites, many extended coiled coil proteins are
      external and bind host proteins. In animals, the majority of extended coiled coil
      proteins were identified as constituents of two protein categories: 1) myosins
      and motors; or 2) components of the nuclear matrix-intermediate filament
      scaffold. This scaffold, produced by sequential extraction of epithelial
      monolayers in situ, contains only 1-2% of the cell mass while accurately
      retaining morphological features of living epithelium and is greatly enriched in
      proteins with extensive, interrupted coiled coil forming domains. The increased
      occurrence of this type of protein in metazoa compared with plants or protists
      leads us to hypothesize a tissue-wide matrix of coiled coil interactions
      underlying metazoan differentiated cell and tissue structure.

PMID- 9162948
TI  - Time-resolved fluorescence study of a calcium-induced conformational change in
      prothrombin fragment 1.
AB  - The wavelength dependent fluorescence decay properties of bovine prothrombin
      fragment 1 have been investigated employing a picosecond time-correlated single
      photon counting technique. All observations are discussed with using the crystal
      structure (Soriano-Garcia et al., Biochemistry 31:2554-2566, 1992). Fluorescence
      lifetimes distribution and conventional multiexponential analysis, as well as
      acrylamide quenching studies lead to the identification of six distinguishable
      tryptophan excited-states. Accessibility to the quencher and the known structure
      are used to associate a fluorescence decay of the tryptophan present in the Gla
      domain (Trp42) with two red shifted components (2.3 and 4.9 ns). The two kringle
      domain tryptophans (Trp90 and Trp126) exhibit four decay times (0.06, 0.24, 0.68,
      and 2.3 ns), which are blue shifted. The calcium-induced fluorescence quenching
      is a result of static quenching: the five decay times remain unchanged, whereas
      the fluorescence intensity of Trp42 is decreased. The static quenching process is
      a consequence of a ground state interaction between the Cys18-Cys23 disulfide
      bridge and Trp42. The monomolecular equilibrium constant for this disulfide-pi
      electron interaction is found as 4.8.

PMID- 9162949
TI  - Ion pair formation of phosphorylated amino acids and lysine and arginine side
      chains: a theoretical study.
AB  - Protein phosphorylation is one of the major signal transduction mechanisms for
      controlling and regulating intracellular processes. Phosphorylation of specific
      hydroxylated amino acid side chains (Ser, Thr, Tyr) by protein kinases can
      activate numerous enzymes; this effect can be reversed by the action of protein
      phosphatases. Here we report ab initio (HF/6-31G and Becke3LYP/6-31G) and
      semiempirical (PM3) molecular orbital calculations pertinent to the ion pair
      formation of the phosphorylated amino acids with the basic side chains of Lys and
      Arg. Methyl-, ethyl-, and phenylphosphate, as well as methylamine and
      methylguanidinium were used as model compounds for the phosphorylated and basic
      amino acids, respectively. Phosphorylated amino acids were calculated as mono-
      and divalent anions. Our results indicate that the PSer/PThr ion pair interaction
      energies are stronger than those with PTyr. Moreover, the interaction energies
      with the amino group of Lys are generally more favorable than with the
      guanidinium group of Arg. The Lys amino groups form stable bifurcated hydrogen
      bonded structures; while the Arg guanidinium group can form a bidentate hydrogen
      bonded structure. Reasonable values for the interaction free energies in aqueous
      solution were obtained for some complexes by the inclusion of a solvent reaction
      field in the computation (PM3-SM3).

PMID- 9162950
TI  - Thurstonian and Brunswikian origins of uncertainty in judgment: a sampling model
      of confidence in sensory discrimination.
AB  - As a preliminary step towards the presentation of a model of confidence in
      sensory discrimination, the authors propose a distinction between 2 different
      origins of uncertainty named after 2 of the great probabilists in the history of
      psychology, L.L. Thurstone and Egon Brunswik. The authors review data that
      suggest that there are empirical as well as conceptual differences between the 2
      modes of uncertainty and thus that separate models of confidence are needed in
      tasks dominated by Thurstonian and Brunswikian uncertainty. The article presents
      a computational model for 1 class of tasks dominated by Thurstonian uncertainty:
      sensory discrimination with pair comparisons. The sensory sampling model predicts
      decisions, confidence assessments, and the complex pattern of response times in
      simple psychophysical discrimination tasks (J.V. Baranski and W.M. Petrusic,
      1994). The model also accounts for the disposition towards underconfidence often
      observed in sensory discrimination with pair comparisons.

PMID- 9162951
TI  - [Impulse conduction and synaptic transmission].

PMID- 9162952
TI  - [Structure, function and regulation of voltage-gated sodium channel].

PMID- 9162953
TI  - [K+ channel].

PMID- 9162954
TI  - [Calcium channels].

PMID- 9162955
TI  - [Inositol 1,4,5-trisphosphate receptor (IP3 receptor)].

PMID- 9162956
TI  - [Ryanodine receptor].

PMID- 9162957
TI  - [Regulation of cation pump activity in nervous system].

PMID- 9162958
TI  - [Aminetransporters].

PMID- 9162959
TI  - [Amino acid neurotransmitter transporters].

PMID- 9162960
TI  - [Molecular mechanisms for neurotransmitter release].

PMID- 9162961
TI  - [Acetylcholine receptor].

PMID- 9162962
TI  - [Molecular diversity and physiological roles of the glutamate receptor channel].

PMID- 9162963
TI  - [Metabotropic glutamate receptors].

PMID- 9162964
TI  - [GABA receptors].

PMID- 9162965
TI  - [ATP receptors].

PMID- 9162966
TI  - [Adrenaline receptor and dopamine receptor].

PMID- 9162967
TI  - [Histamine receptors].

PMID- 9162968
TI  - [Opioid receptors].

PMID- 9162969
TI  - [Peptide receptors].

PMID- 9162970
TI  - [Signal transduction in the cells].

PMID- 9162971
TI  - [Alpha beta gamma-heterotrimeic GTP-binding proteins].

PMID- 9162972
TI  - [Rab3A and neurotransmitter release].

PMID- 9162973
TI  - [Structure and regulation of adenylyl cyclase].

PMID- 9162974
TI  - [Function of soluble guanylate cyclase and nitric oxide].

PMID- 9162975
TI  - [New members of regulating phosphoinositide metabolism].

PMID- 9162977
TI  - [Physiological roles of cyclic nucleotide dependent protein kinases in advanced
      brain functions].

PMID- 9162976
TI  - [Phosphoinositide 3-kinase].

PMID- 9162978
TI  - [Protein kinase C in neuronal signaling].

PMID- 9162979
TI  - [CaM kinase cascade].

PMID- 9162980
TI  - [The MAP kinase cascade].

PMID- 9162981
TI  - [The functions of tyrosine kinases in the neuronal tissues].

PMID- 9162982
TI  - [Roles of protein Ser/Thr phosphatases in regulation of neural cell functions].

PMID- 9162983
TI  - [Protein tyrosine phosphatases in the neural system].

PMID- 9162984
TI  - [Cytoskeletons in the signal transduction].

PMID- 9162985
TI  - [Neurotrophic factor and cytokine].

PMID- 9162986
TI  - [Neurotrophins and their receptors].

PMID- 9162987
TI  - [Neurotrophin and synaptic plasticity].

PMID- 9162988
TI  - [Glial cells-derived neurotrophic factors].

PMID- 9162989
TI  - [Ciliary neurotrophic factor and leukemia inhibitory factor].

PMID- 9162990
TI  - [Cytokine network in the brain].

PMID- 9162991
TI  - [Cytokines as signal transmitters in the nervous system].

PMID- 9162992
TI  - [Review of neural cell adhesion molecules].

PMID- 9162993
TI  - [Role of cadherin adhesion systems in selective synapse formation].

PMID- 9162994
TI  - [Expression and function of neural cell adhesion molecule (NCAM) and its
      polysialic acid moiety in the nervous system].

PMID- 9162995
TI  - [L1 and P0 proteins].

PMID- 9162996
TI  - [SC1].

PMID- 9162997
TI  - [Telencephalin, a dendrite-associated cell adhesion molecule with brain segment
      specific expression].

PMID- 9162998
TI  - [Gicerin].

PMID- 9162999
TI  - [Neural proteoglycans: neuroglycan C (NGC), neurocan, and phosphacan].

PMID- 9163001
TI  - [The action of reelin in the layering of cortical neurons in cerebrum].

PMID- 9163000
TI  - [Netrin and semaphorin].

PMID- 9163002
TI  - [Roles of neuropilin and plexin in the development of nervous system].

PMID- 9163003
TI  - [Gene expression and the regulation in brain (discussion)].

PMID- 9163004
TI  - [Myocardial infarction--symptoms and procedures. Longitudinal observation of a
      population of 280,000 women and men--Project POL-MONICA Krakow. V. Atypical
      symptoms and prognosis in myocardial infarction].
AB  - There is some evidence in Poland, that percent of hospitalized coronary heart
      disease events with no typical pain for myocardial infarction (MI) increased. The
      purpose of the paper was to assess in the observational study whether the lack of
      typical pain in MI effects the risk of death in the acute phase. There were 1815
      events, registered in POL-MONICA Krakow Project, with clinical diagnosis of MI or
      acute coronary heart disease, which were classified as "definite MI" or "possible
      MI" according to the criteria of The WHO MONICA Project, which were included to
      the analysis. Typical pain occurred in 1693 (93%) events and atypical symptoms in
      122 (7%) events. Shock and left ventricular failure (LVF) were observed more
      frequently in patients with atypical symptoms who also were treated more
      frequently with diuretics, inotropic agents, antiarrythmics and more frequently
      received thrombolytic treatment. Patients with atypical symptoms had higher risk
      of death. Relative risk was 3.65 (95% confidence interval: 2.45-5.44). After
      adjustment for age, sex, shock, LVF and diabetes relative risk decreased to 1.67
      (95% confidence interval: 1.10-2.54) and after inclusion of treatment to the
      analysis relative risk decreased to 1.58 (95% confidence interval: 1.04-2.39).
      The results suggest that lack of typical pain in MI can be related to worse
      prognosis and it should lead to more careful consideration of the treatment.

PMID- 9163005
TI  - [Myocardial infarction--symptoms and procedures. Longitudinal observation of a
      population of 280,000 women and men--Project POL-MONICA in Krakow. VI: Enzymatic
      diagnosis and myocardial infarction].
AB  - Different combinations of serum enzymes activity determinations are used in the
      diagnostics of myocardial infarction. The goal of the present paper was: 1) to
      assess the frequency of determinations of asparagine aminotransferase (AspAT) and
      to compare it with the frequency of determinations of creatinine phosphokinase
      (CPK) in patients hospitalized due to ischaemic heart disease in district
      hospitals, and 2) to assess to what extent the parallel determination of both
      enzymes effected to diagnostic classification of events according to The WHO
      MONICA Project. The analysis was done in 7406 hospitalized events registered with
      the clinical diagnosis of ischaemic heart disease (1810 myocardial infarctions,
      402 acute coronary heart disease and 5194 other forms of ischaemic heart
      disease), registered in POL-MONICA Krakow Project in 1988-1993. Serum activity of
      AspAT was determined in over 90% events with either myocardial infarction or
      acute coronary heart disease. Number of determinations of CPK increased since
      1990 and then, fluctuated from 15% to 36%. In 718 hospitalized events with
      clinical diagnosis of ischaemic heart disease, for whom both CPK and AspAT were
      determined, there was 96% observed agreement between diagnostic classification of
      events based on complains, ecg and alternatively: 1) both AspAT and CPK and 2)
      CPK only. Potential agreement beyond chance-kappa was 0.94 (almost perfect
      agreement). The parameters of the agreement were worse when AspAT only was used
      in the second option. The results indicate that efforts to increase the number of
      determinations of CPK in myocardial infarction diagnostics should be undertaken.
      At least for a part of events with myocardial infarction diagnosis confirmed by
      ecg and CPK tests, determination of AspAT is not necessary.

PMID- 9163006
TI  - [Analysis of psychosocial factors in epidemiologic study of cardiologic
      examination--preliminary results of Warsaw POL-MONICA].
AB  - Several epidemiological studies have focused on influence of psychosocial factors
      on intensity of cardiovascular diseases in general population. In 1988 Warsaw POL
      MONICA PROJECT was performed covering the population of 710 men and 723 women,
      aged 35-64. We found that 25.1% men and 25.8% women had type A behaviour pattern
      (TABP). TABP was rare represented in the older age group and in low-educated
      persons. Extreme sleep disturbances were observed significantly (p < 0.001) more
      often in women (10.7%) than in men (4.9%) and the percentage increased with age.
      Extreme sleep disturbances were also found more often among elementary educated
      persons (16%) versus the others (p < 0.001). Low social support level was
      observed twice often in women (29.7%) than in men (14.8%) and the percentage
      increased with age and with lower education level (p < 0.001). Extreme stress
      level was found more often in women (13.3%) than in men (5.6%) (p < 0.001) and in
      the oldest age-group. In both sex-groups mean anger levels decreased with age (p
      < 0.05). Mean anxiety levels didn't differ significantly neither in age-groups
      nor in education categories.

PMID- 9163007
TI  - [Effect of furosemide on transperitoneal transport of guanidine derivatives: in
      vitro studies].
AB  - The transperitoneal transport dynamics (removal) of guanidinoacetic acid (GAA)
      and guanidinosuccinic acid (GSA) has been determined in vitro in the control
      conditions and after application of furosemide (10(-4) mmol/l) on the mesothelial
      side of the membrane. GAA peritoneal transfer values, as a rule, were higher than
      GSA and equaled at mean, in the control series of experiments 0.132 i 0.068 mg x
      10(-4) x cm-2 x s-2, respectively. Furosemide decreased GSA passage in 30 min
      after it addition by about 30%, but GSA transfer diminished later, in 120 min.,
      by about 37%. Therefore, mean GAA transport values before (30-90 min.) and after
      application of furosemide (120-210 min.) were not statistically significant
      differentiated, whereas GSA transport parameters were lowered by about 40%.
      Heterogeneity of the peritoneal GAA and GSA transport dynamics in the control
      series of the experiments, as well as in the series with furosemide, may be
      related to the physico-chemical differences (e.g. molecular mass) of the analysed
      derivates.

PMID- 9163008
TI  - [The effect of administering Omega-3 acids on lipids in serum, functional state
      of erythrocyte membrane and function of the kidneys in patients with primary
      glomerulonephritis].
AB  - There are reports concerning profitable influence of unsaturated acids
      administration on blood pressure, inflammation and proteinuria. The aim of
      presented study was to estimate the effect of Omega-3 on plasma lipids and renal
      function in patients with primary glomerulopathies. The tested group consisted of
      13 patients (7F and 6M) aged from 22 to 60 years, with primary glomerulopathies
      and normal renal function. They received Omega-3 (Fishproduct, iceland) 3 x 2
      caps for three months. Before, after 2 and 3 months of treatment and 3 months
      after its discontinuation following parameters were estimated: total cholesterol,
      HDL and LDL cholesterol (HDL, LDL), triglycerides and an order parameter of
      erythrocyte lipid bilayer (S). Simultaneously N-acetylglutamate (NAG), creatinine
      clearance and 24-hours proteinuria were measured. For calculation t-Student test
      was used. In our study we found statistically significant increase of HDL after 2
      and 3 months and decrease of LDL after 3 months of Omega-3 administration (p <
      0.05). During the 2 and 3 months of treatment statistically significant decrease
      of NAG was noticed but a month after its discontinuation significant increase of
      NAG excretion was observed (p < 0.05). The S parameter in tested group of
      patients was higher than in healthy population but during Omega-3 administration
      the value of an order parameter of erythrocyte bilayer increased significantly (p
      < 0.01). On the base of given results we could conclude that unsaturated acids
      may have profitable influence on plasma lipids, functional status of erythrocyte
      membrane and probably proximal tubule function in patients with primary
      glomerulopathies.

PMID- 9163009
TI  - [Albumin excretion with urine in a population of healthy individuals].
AB  - Increased urine albumin excretion is the significant prognostic factor for
      diabetes, hypertension and coronary artery disease. Divergences of the evaluation
      of albuminuria in different ethnic groups were found. The aim of our study was to
      evaluate albumin excretion in large group of healthy individuals. 301 healthy
      subjects (110 female and 191 male), age 20-60 years (mean 32.9 +/- 9.7), were
      admitted. A questionnaire including data concerning familial history, smoking
      habits was fulfilled. Subsequently nighttime urine sample was collected in all
      examined subjects and albumin to creatinine ratio (A/K) was counted. A/K value
      varied between 0.03-14.1 mg/mmol of creatinine median 1.18. Significantly higher
      albuminuria in female v male group was found (respectively 1.39; 0.14-14.1 and
      1.03; 0.03-11.4 p < 0.05). Reference value for albuminuria was estimated at 3.35
      mg/mmol in whole group, and respectively 4 mg/mmol in female and 2.6 mg/mmol in
      male. There were not differences in A/K ratio in relation to familial history
      however smoking men excreted more albumin v non smoking (respectively 1.27, 0.03
      11.4 and 0.95, 0.14-14.1 mg/mmol p < 0.005). Performed analysis allowed to
      calculate the value for albuminuria in healthy subjects. Analysis also showed
      significant influence of gender and smoking habits and no influence of familial
      history for albumin excretion.

PMID- 9163010
TI  - [Requirement for blood in hemodialyzed patients with chronic renal failure in the
      period before and after introduction to erythropoietin (r-HuEPO) treatment].
AB  - The present paper aimed to assess the influence of EPO-therapy on the requirement
      of blood transfusion in haemodialysed patients with end-stage renal failure. As
      shown in this paper, introduction of r-HuEPO into the therapy of uraemic anaemia
      almost completely eliminated the request for blood transfusion in these patients.
      EPO therapy did not influence significantly to the serum creatinine concentration
      and mean arterial blood pressure in these patients.

PMID- 9163012
TI  - [Neuroendocrine Merkel's tumor].

PMID- 9163011
TI  - [Toxicity and efficacy of chemotherapy dependent on circadian time of cytostatic
      drug administration].
AB  - A prospective, controlled study was carried out in order to evaluate efficacy and
      toxicity of chemotherapy based on cisplatin in dependence on the circadian rhythm
      of drugs administration in patients with testicular and ovarian cancer. The study
      included 80 patients (40 with testicular cancer and 40 with ovarian cancer),
      divided into two groups (A and B). The cytostatics were administered in the
      evening in the group A and in the morning in the group B. The response rates and
      the 3-years survival rates were comparable in both groups. However the patients
      in the group A presented less haematological and renal side effects, while nausea
      and vomiting were milder. Chronotherapy may appear to be a method improving the
      tolerance of chemotherapy based on cisplatin.

PMID- 9163013
TI  - [Appendiceal abscess in the third gestational trimester of pregnancy,
      complications pre and postoperatively].
AB  - Delayed surgical intervention connected with misdiagnosis of preterm labour and
      urinary tract infection caused in gravida 3 in 34th gestational week appendiceal
      abscess, septic shock, stillbirth by cesarean section, necessity of hysterectomy,
      recidivism of multi peritoneal and pleural abscesses. Although the patient was
      rescued the retrospective pro memoria considerations of our procedure are
      regarded.

PMID- 9163014
TI  - [Glycol ethylene poisoning as a cause of chronic renal failure].
AB  - There were shown some observations from two Dialysis Centres concerning acute
      Ethylene Glycol poisoning and four cases of chronic renal failure progress. The
      renal biopsy made at one patient and our clinical observations indicate for
      possibility of chronic renal failure development in some pts. There were
      discussed hypothesis of CRF development at these pts.

PMID- 9163015
TI  - [Medico-legal circumstances of organ transplantation in Poland (history and
      present state)].

PMID- 9163016
TI  - [Jan Ewangelista Purkynie, and the Annals of the the Medical Faculty].
AB  - Jan Ewangelista Purkyne, the founder of the modern physiology and histology,
      professor of the University in Wroclaw (1823-1850), deserve a reward not only to
      the Czech national culture, but also made much to approach our countries. But
      what is less known is the fact concerning his cooperation with Annals of the
      Medical Faculty in Jagiellonian University and his additional office professors
      Jozef Majer and Franciszek Skobel. This first publication on the subject of
      cardiacl conductional fibres, later caller Purkyne's fibres reveals in the second
      volume of Annals of Medical Faculty in Jagiellonian University AD 1839, six years
      before the publication in German. Boguslaw Palicki was one of the fourteen
      doctoral students Wroclaw Physiological School J.E. Purkyne. It is necessary to
      underline not only Purkyne vivid connection with eminent personage in those days
      of European science-with Cracow colleagues and his research organ-but also a high
      scientific and additional standard of Annals, which ended their life with the
      fall of the Cracow Republic AD 1846. Purkyne's studies and discoveries also in
      the present time are of lasting scientific as well as medico-historical values.

PMID- 9163017
TI  - Herpes virus infections. Proceedings of a meeting. Stockholm, Sweden, 11-12 May
      1995.

PMID- 9163018
TI  - Herpes simplex virus and pregnancy.
AB  - Although herpes simplex virus (HSV) infections are common in pregnant women, they
      are rarely serious. The complication, however, is viral transmission to the
      infant and morbidity and mortality in neonatal herpes remains considerable, in
      spite of the availability of antiviral therapy. Early recognition and treatment
      of the infected child is of the utmost importance to inhibit viral replication
      and thus limit the severity of the disease. Moreover, prevention is the ultimate
      challenge. Unfortunately, in many cases this is not achievable since the
      infection in the mother and child often presents without typical herpes symptoms.
      This was illustrated in a follow-up study of neonatal herpes in Sweden. In nearly
      half of the cases of neonatal herpes, neither mother nor child had typical herpes
      symptoms. The herpes simplex virus type 2 (HSV-2) infections were more often
      atypical or asymptomatic in nature in the mother and child than the HSV-1
      infections. Outcome was more serious in HSV-2 infections, and a large proportion
      of children with this type did not have skin lesions. Neonatal herpes transmitted
      from recurrent maternal infection had a long incubation period (mean 14 days) and
      was often localized to the brain. Disease due to primary infection was
      disseminated, with a mean incubation time of 6 days. Preventive strategies are
      discussed. In the majority of cases, clinical recognition of risk factors for
      transmission in the mother--a prerequisite for preventive measurements --is not
      possible.

PMID- 9163019
TI  - Limiting the spread of genital herpes.
AB  - In many western countries, successful control of bacterial sexually transmitted
      diseases (STDs) has contrasted with an increase in the prevalence of viral STDs.
      The continued increase in clinical and subclinical genital herpes infections is
      of particular concern because of the implications for the risk of coincident
      spread of human immunodeficiency virus infection. Advances in knowledge of the
      epidemiology and natural history of genital herpes must be the basis of renewed
      educational efforts targeted at the general public, healthcare professionals, as
      well as infected persons. Diagnostic techniques, such as polymerase chain
      reaction and type-specific serology, now allow increased detection of subclinical
      infection. However, infected persons must be assured of access to effective
      antiviral treatment and comprehensive holistic management if the clinical and
      epidemiological benefits of detection are to outweigh the psychological and
      psychosocial disadvantages of being infected with a stigmatized condition.
      Vaccines could offer the best prospect for both primary prophylaxis and
      immunotherapy of genital herpes, and may have the greatest impact in limiting the
      spread of this infection. Recent progress has been made in the development of
      effective and safe vaccines, and their successful introduction should be a major
      priority over the next decade.

PMID- 9163020
TI  - Psychological and psychosexual implications of herpes simplex virus infections.
AB  - Genital herpes causes considerable psychological and psychosexual morbidity. The
      most common emotional responses are depression, anguish, anger, diminution in
      self-esteem and hostility towards the person believed to be the source of the
      infection. These emotional problems appear to be worse in women than in men. The
      psychological morbidity in patients with first episode genital herpes is
      statistically significantly greater than that occurring in non-herpes patients
      attending sexually transmitted disease clinics. It was previously believed that
      stressful life events could precipitate recurrences. However, recent studies
      suggest that ongoing recurrences cause the emotional stress rather than vice
      versa. There is some evidence that premorbid personality may effect recurrence
      rates, but an equally plausible explanation is that frequent recurrences
      adversely affect personality. Long-term aciclovir suppression significantly
      reduces the psychological morbidity associated with recurrent genital herpes,
      over at least the period of treatment. Cognitive coping strategies and social
      support from a partner appear to assist with adjustment. Improving a patient's
      problem-solving skills, and long-term aciclovir therapy should form an integral
      part of the long-term management of recurrent genital herpes.

PMID- 9163021
TI  - Herpesviruses and AIDS.
AB  - It is well recognized clinically that herpesviruses can cause disease in AIDS
      patients once human immunodeficiency virus (HIV) has precipitated marked
      immunosuppression. However, in addition to this opportunistic relationship, there
      is evidence to suggest that herpesviruses could increase the pathogenicity of HIV
      by acting as cofactors. Experiments in vitro have shown that several
      herpesviruses can activate HIV gene expression or alter the cellular tropism of
      HIV through a variety of mechanisms (antigen presentation, cytokine release,
      pseudotype formation, CD4 cell surface upregulation, Fc receptor formation,
      transactivation). Studies of human autopsy material have shown that some
      herpesviruses (particularly cytomegalovirus, human herpes virus 6 and herpes
      simplex virus) are found frequently in AIDS patients. If such herpesviruses act
      as cofactors in vivo, then their inhibition by aciclovir could explain why a
      survival benefit has been reported from the use of this drug in two double-blind,
      placebo-controlled randomized trials.

PMID- 9163022
TI  - The Swedish telephone herpes helpline.
AB  - To increase the accessibility of qualified and anonymous advice on herpes
      infections in Sweden, a telephone counselling service was initiated in November
      1994. The nucleus of the service is an answering machine that works around the
      clock. A caller can choose one of 3 different messages dealing with labial or
      genital herpes infection or herpes zoster--each message is approximately 3 min
      long. Those wanting written information can register and have material sent to
      them. For 2 h daily, 4 days a week, calls pass directly to the staff of the
      sexually transmitted diseases clinic of the University Hospital in Uppsala,
      Sweden--the caller pays only a single telephone unit charge. The personal calls
      deal with all aspects of herpes infections. During the first 3 months of the
      counselling service more than 4,500 calls were received.

PMID- 9163023
TI  - Neurological complications in herpes zoster.
AB  - This paper discusses the complications associated with herpes zoster, with
      emphasis on its neurological manifestations. These complications, which are
      particularly prevalent in elderly and immunodeficient patients, include focal
      muscle paralysis, contralateral hemiplegia, myelitis, cranial nerve palsies and
      meningoencephalitis. A causative relationship with herpes zoster in many of these
      syndromes is probably more common than previously suspected due to difficulties
      in diagnosis and lack of awareness among clinicians. Zoster sine herpete--
      reactivation of varicella zoster virus without rash--is associated with a
      spectrum of neurological disease and, for obvious reasons, is particularly
      difficult to diagnose. The polymerase chain reaction could be a valuable tool in
      overcoming these diagnostic problems, especially in patients without
      characteristic eruptions, allowing the early initiation of effective antiviral
      therapy.

PMID- 9163024
TI  - Polymerase chain reaction for diagnosis of varicella zoster virus central nervous
      system infections without skin manifestations.
AB  - Varicella zoster virus (VZV) can cause disease in the central nervous system
      (CNS) during both primary infection and reactivation. Rapid and adequate
      diagnosis of VZV have previously been hampered by the shortcomings of standard
      virological methods, such as isolation and serology. Earlier reported cases of
      CNS manifestations of VZV infection have, therefore, mostly been noted in
      connection with, or shortly after, onset of vesicular rash. Several studies have
      recently been described of cases of VZV-induced CNS disease occurring as the only
      sign of viral reactivation, with the diagnosis aided by polymerase chain reaction
      (PCR) amplification and other methods of genome detection. A prospective study
      was performed using PCR on cerebrospinal fluid (CSF) and brain samples received
      for routine diagnosis of possible VZV infection during a 2-year period. Samples
      from 8 (7 from CSF, 1 from brain) of the 260 patients investigated (3.1%) were
      found to be positive for VZV-DNA. All 8 had a presumed reactivated VZV infection
      according to serological and clinical analysis. Their CNS manifestations ranged
      from meningitis to severe encephalitis, and only in 3 of these patients was a
      vesicular rash present. Thus, VZV-DNA detection in the CSF was an unexpected
      finding for the clinician and, in 2 cases, antiviral treatment with aciclovir was
      initiated only because of the PCR evidence of CNS infection. VZV should be
      considered as a possible causative agent of infection in patients with CNS
      disease of suspected viral origin, even in the absence of skin manifestations.
      Rapid diagnosis by PCR amplification of VZV-DNA from CSF might allow for early
      and adequate antiviral treatment.

PMID- 9163025
TI  - Latency and reactivation of varicella zoster virus infections.
AB  - Varicella zoster virus (VZV) is the causative agent of chickenpox (varicella) and
      shingles (zoster). The study of latency and reactivation has been hampered by the
      fact that the virus is strictly human and grows to low titres in tissue culture.
      Molecular biology techniques have opened a new era of VZV research. The site of
      VZV latency was determined to be sensory ganglia by Southern blotting and later
      by PCR technology. It was also demonstrated that the entire virus genome is
      present in the latently infected ganglia and that VZV is latent in multiple
      ganglia along the entire human neuraxis. Since the amount of latent VZV per cell
      is very low, the question of which cell type is involved in VZV latency could not
      be conclusively settled by the use of traditional in situ hybridization studies.
      However, we have now demonstrated the presence of latent VZV DNA in neurons only,
      by using a more sensitive method which employs a combination of in situ PCR and
      in situ hybridization. The transcriptional activity of VZV during latency is
      still not completely clear. Ganglia are small and the total amount of latent VZV
      is low, therefore conventional methods to detect latent VZV have proved limited.
      Nevertheless, the detection of a latent transcript from the SalI C region of the
      virus was demonstrated by Southern hybridization of cDNA synthesized from RNA
      isolated from latently-infected ganglia. Further studies have localized this
      transcript to the open reading frame of VZV gene 21. The study of VZV latency and
      reactivation has, until now, been dependent on the investigation of post mortem
      human tissue. However, simian varicella virus seems to be the simian counterpart
      to human VZV. The 2 viruses exhibit DNA homology as well as similarities in
      clinical, virological, and immunological features. Further studies of VZV
      infections may open new and possibly unpredictable opportunities in varicella
      virus research.

PMID- 9163026
TI  - Antiviral drugs in development for herpes zoster.
AB  - Until recently aciclovir has been the only licensed drug for the treatment of
      herpes zoster. A number of new drugs have emerged over the past few years which
      offered the potential for improved efficacy or ease of administration. With the
      completion of the first efficacy trials for each of these agents it has become
      apparent that, whilst less frequent dosing can he accomplished, it is not easy to
      significantly improve on the efficacy of aciclovir. Increasing age, the presence
      of prodromal pain and more severe pain at presentation have, however, been found
      to predispose to a longer duration of pain. Taking cessation of pain as the
      single most important parameter, at least for the older immunocompetent
      population as a whole, only valaciclovir has, to date, been shown to be superior
      to standard therapy with aciclovir. This review utilises primarily intent-to
      treat data to illustrate the relative efficacy of the different therapies.

PMID- 9163027
TI  - Herpes simplex encephalitis.
AB  - Herpes simplex encephalitis (HSE) is a life-threatening condition with high
      mortality as well as significant morbidity in survivors. In most cases herpes
      simplex virus type 1 (HSV-1) is responsible for the diseases, however, the type 2
      virus (HSV-2) is involved in 4-6% of cases. Primary HSV infection is identified
      in only one-third of patients with HSE. The majority of cases are recorded in
      adults with recurrent HSV infection who are already seropositive for HSV at the
      onset of symptoms, but only 6-10% of these patients have a history of labial
      herpes. Acute focal, necrotizing encephalitis with inflammation and swelling of
      the brain tissue are consistent features of the pathology of HSE. HSV-induced
      cytolysis certainly damages neurones, oligodendrocytes and astrocytes, but the
      role of cellular and humoral immunopathology is important. A complex network of
      cytokines seems to be active in regulating the local immune response and
      inflammation during and after HSE. Brain biopsy, serological analysis of
      intrathecal HSV antibodies and detection of HSV-DNA in the cerebrospinal fluid
      (CSF) are all useful techniques to confirm the aetiology of HSE. Neurodiagnostic
      tests which support a presumptive diagnosis of HSE include: CSF analysis,
      electroencephalography, computer-assisted tomography and magnetic resonance
      imaging. Although aciclovir is the treatment of choice in HSE, mortality and
      morbidity still remain problematic. Long-term follow-up indicates that
      intrathecal cellular and humoral activation persist in HSE.

PMID- 9163028
TI  - Testing the power of belief.

PMID- 9163030
TI  - Testing the power of belief.

PMID- 9163029
TI  - Testing the power of belief.

PMID- 9163031
TI  - NIH plans peer-review overhaul.

PMID- 9163032
TI  - Whitehead, three firms splice a deal.

PMID- 9163033
TI  - Watson urges 'put Hitler behind us'.

PMID- 9163034
TI  - Bone sizes trace the decline of man (and woman)

PMID- 9163035
TI  - Stubborn AIDS reservoirs vulnerable to new treatments.

PMID- 9163036
TI  - Adaptation by hyperpolarization.

PMID- 9163037
TI  - Ozone pollution in the rural United States and the new NAAQS.

PMID- 9163038
TI  - Surface composition of Kuiper belt object 1993SC.
AB  - The 1.42- to 2.40-micrometer spectrum of Kuiper belt object 1993SC was measured
      at the Keck Observatory in October 1996. It shows a strongly red continuum
      reflectance and several prominent infrared absorption features. The strongest
      absorptions in 1993SC's spectrum occur near 1.62, 1.79, 1.95, 2.20, and 2.32
      micrometers in wavelength. Features near the same wavelengths in the spectra of
      Pluto and Neptune's satellite Triton are due to CH4 on their surfaces, suggesting
      the presence of a simple hydrocarbon ice such as CH4, C2H6, C2H4, or C2H2 on
      1993SC. In addition, the red continuum reflectance of 1993SC suggests the
      presence of more complex hydrocarbons.

PMID- 9163039
TI  - [The dynamics of ischemic heart disease and the risk factors among the male
      population of Moscow in the 1985 to 1995 period].
AB  - The trends in prevalence of ischemic heart disease (IHD) and risk factors for
      1985-1995 have been studied on random representative samples of male population
      from Moscow. For the decade studied IHD incidence increased, especially in
      younger males. Changes in IHD risk factors were the following: systolic and
      diastolic pressures were on the increase. HDLP cholesterol and total cholesterol
      in the blood lowered, total triglycerides were unchanged, incidence of smoking
      remained high.

PMID- 9163040
TI  - [The effect of a 5-year program of IHD prevention on the risk profile and
      mortality].
AB  - Multifactorial prophylaxis on the individual basis was conducted for 5 years
      among the population of 2047 males aged 40-59 years with ischemic heart disease
      (IHD) or its risk factors. Compared to the comparison group of 2101 subjects, in
      the study group the investigators achieved a 37% reduction in the mean population
      profile of myocardial infarction risk due to less prevalence of 3 main risk
      factor: arterial hypertension, low physical activity, smoking. Unbalance of the
      groups by age and education made the effect of the prevention measures on
      cardiovascular mortality menostrable only at statistical Cox's model.

PMID- 9163042
TI  - [The pathogenetic problems of atherosclerosis: the regional aspects].

PMID- 9163041
TI  - [The therapeutic and prophylactic use of Olicard-Retard under outpatient
      polyclinical conditions in stenocardia patients].
AB  - Olicard-Retard, isosorbide-5-mononitrate drug, has been tried in a single daily
      dose 40 mg in 60 outpatients with angina pectoris. The drug reduced the frequency
      of anginal attacks and nitroglycerine intake in most of the patients. The
      antianginal properties were combined with anti-ischemic effects as shown by
      echocardiography. Side effects (head ache) were mild. Olicard-Retard proved
      effective in angina of effort both in monotherapy and combined treatment.

PMID- 9163043
TI  - [Total and lipid-bound sialic acids in the blood in primary and secondary
      hyperlipoproteinemias].
AB  - Total and lipid-bound sialic acids (TSA and LBSA) were measured in the blood of
      219 patients with primary or secondary hyperlipoproteinemia (129 patients with
      ischemic heart disease and 66 patients with diabetes mellitus type II) versus 24
      normolipidemic healthy subjects. TSA levels in IHD patients differed
      significantly from those in IHD-free and diabetic patients. LBSA quantities were
      the same in IHD and IHD-free patients, being significantly higher in diabetes
      mellitus than in IHD. These findings give no proves to diagnostic value of TSA
      and LBSA as markers of IHD and coronary atherosclerosis. TSA levels may be used
      in the test for disturbed lipoprotein metabolism.

PMID- 9163044
TI  - [The characteristics of the blood lipid composition in northern Selkups and in
      the immigrant population of northern Siberia and the problems of miscegenation].
AB  - Blood lipid composition was studied in 507 Selkups, native population of Tyumen
      Province (199 males and 308 females), 245 Slavs living in the north for more than
      5 years (97 males and 148 females), 189 first generation metis born in mixed
      marriages (68 males and 121 females). Three age groups were analyzed: 10-19
      (group 1), 20-39 (group 2), 40-59 (group 3). Male metis from groups 1, 2 and 3
      had the highest levels of HDLP cholesterol, the lowest of apoB and atherogenic
      index. Group 2 metis were in the intermediate position between Slavs and Selkups
      by concentrations of total and LDLP cholesterol and triglycerides. Group 3 metis
      males had the lowest levels of triglycerides and intermediate levels of total and
      LDLP cholesterol. Group 1 and 2 metis females had the highest levels of LDLP, the
      lowest of apoB and low atherogenic index. In group 3, levels of total
      cholesterol, LDLP cholesterol, apoB and atherogenic index were as high as in non
      aboriginal Slavonic population.

PMID- 9163045
TI  - [The Lewis antigen system as a marker of IHD risk].
AB  - Prevalence of Lewis antigens and phenotypes has been investigated in 60 healthy
      donors and 74 patients with ischemic heart disease. It was found that phenotype
      Le(a-b-) marks high risk and phenotype Le(a-b+) is a resistance marker for
      development of ischemic heart disease. It would be valid to elucidate
      relationships between Lewis system and pathogenesis of internal diseases.

PMID- 9163046
TI  - [Physical work capacity as an independent risk factor for the development of
      arterial hypertension].
AB  - Whether an independent relationship exists between muscular performance (MP) and
      arterial pressure (AP) was investigated in subjects with normal AP, borderline AP
      and arterial hypertension using different variants of the parameters distribution
      and link (maximal, minimal MP, normal AP, borderline AP, hypertension with sex
      and age ranges 30-39, 40-49, 50-59, 60-69). It was found that: AP significantly
      increases with MP lowering, age is not a key factor in relations between MP and
      AP, MP is an independent factor of the hypertension risk, the risk of
      hypertension declines with growing MP.

PMID- 9163047
TI  - [An analysis of the indices of ambulatory circadian blood pressure monitoring in
      patients with arterial hypertension].
AB  - The authors have found that more accurate prognosis of left ventricular
      myocardial hypertrophy (LVMH) may be made basing on fluctuations and variability
      of arterial pressure throughout the day: significant fluctuations of arterial
      pressure at night and pronounced variability of systolic arterial pressure in the
      day time and at night are indicative of essential hypertension instability and
      may contribute to LVMH progression. Of still greater prognostic significance is
      assessment of 24-h arterial pressure rhythm by the degree of a night fall (DNF)
      in diastolic arterial pressure (DAP). A disturbed 24-h rhythm of arterial
      pressure (a fall in DNF of DAP) is a predictor of LVMH development.

PMID- 9163048
TI  - [The prevention of cerebral circulatory disorders in arterial hypertension].

PMID- 9163049
TI  - [The effect of long-term uncontrolled antihypertensive therapy on the
      echocardiographic signs of left-heart hypertrophy in patients with mild and
      moderate arterial hypertension].
AB  - The data are presented on the absence of a stable positive trend in
      echocardiographic characteristics of the left heart and intracardiac hemodynamics
      after 8 months of controlled antihypertensive therapy, 12-month follow-up and
      uncontrolled outpatient treatment. 12 months after discontinuation of controlled
      antihypertensive therapy arterial pressure was much higher than it was at the end
      of the treatment in patients taking antihypertensive drugs irregularly or not
      taking them at all. Intracardiac hemodynamics returned to the baseline. As shown
      by echo-CG, frequency of left ventricular hypertrophy 12 months after the end of
      antihypertensive treatment rose from 25.8 to 45.2% (p < 0.01), of right
      ventricular hypertrophy from 14.5 to 17.7%.

PMID- 9163050
TI  - [The characteristics of cardiac diastolic function in myocardiodystrophy in
      persons subjected to aromatic hydrocarbon exposure].
AB  - Left and right ventricular diastolic function was investigated at doppler
      echocardiography in patients with myocardiodystrophy exposed to organic aromatic
      solvents (30 female house painters). The control group consisted of healthy
      females and females with autonomic-dyshormonal myocardiodystrophy. The study
      group exhibited diastolic dysfunction characterized by disturbed active
      relaxation assessed by duration of isometric left and right ventricular
      relaxation.

PMID- 9163051
TI  - [The diagnosis of prognostically unfavorable variants of the premature
      ventricular excitation syndrome].

PMID- 9163052
TI  - [Polyclinical therapy--an essential part of the study of internal diseases (on
      the centenary of the Department of Outpatient Care of Internal Diseases)].

PMID- 9163053
TI  - [Experience in treating patients with cardiovascular diseases by means of
      adaptation to periodic barochamber hypoxia].
AB  - Adaptation to periodic hypoxia (decompression 490 mm Hg) in a multiplace medical
      pressure chamber of patients with hypertension, cardial neurocirculatory
      asthenia, coronary heart disease produced a persistent hypotensive effect with
      improvement of central and peripheral hemodynamics, oxygen homeostasis,
      electrolyte balance of blood. In patients with neurocirculatory asthenia
      associated with ventricular and supraventricular extrasystole positive
      hemodynamic changes accompanied a persistent antiarrhythmic effect. In addition
      to the latter, CHD patients experienced improvement in myocardial contractility.
      Clinical effect of baroadaptation to hypoxia manifesting in symptom relief
      permitted the physicians to diminish the intensity of chemotherapy and to abolish
      it in patients with neurocirculatory asthenia.

PMID- 9163054
TI  - [The effect of rehabilitation by stages at a low-altitude health resort on the
      late results of the surgical treatment of ischemic heart disease].

PMID- 9163055
TI  - [The efficacy of the macrolide antibiotic rovamycin in treating acute pneumonia].

PMID- 9163056
TI  - [The characteristics of the blood lipid transport system in the disabled with
      lost lower extremities].
AB  - A comparative analysis of major blood lipoprotein values in 108 males aged 16-65
      years with lower limbs amputations has shown a higher level of triglycerides (TG)
      and a reduced level of high density lipoprotein cholesterol (HDL C) in them than
      in control males with normal limbs. In the subgroup of patients who had undergone
      the amputation as a result of obliterative arterial disease, the TG level was the
      highest while HDL C the lowest; moreover, these values appeared to be the same as
      in the age-matched subgroup of patients with manifestations of atherosclerosis.
      In the subgroup of older men with posttraumatic lower limb amputations (aged 40
      59 years) the TG and HDL C levels did not differ from the corresponding
      parameters in age-matched subgroup of healthy subjects, whereas young amputees
      (17-39 years) had the increased blood TG concentration and reduced level of HDL C
      and apolipoprotein AI. The conclusion is made: disability following limb
      amputation accompanied by restricted mobility, inadequate physical static efforts
      as well as by chronic psychological stress seem especially dangerous for young
      invalids because of associated lipoprotein profile changes which can be regarded
      as highly atherogenic.

PMID- 9163057
TI  - [Halcion (triazolam) in the treatment of insomnia].
AB  - A hypnotic effect of chalcion (triazolam) was studied in 24 outpatients suffering
      from insomnia. It was found high and beneficial in pre-, intra- and post
      insomniac disorders. Side effects were mild. Characteristics of chalcion-induced
      sleep reached to those of physiological sleep. Chalcion was found superior to
      other drugs used against insomnia.

PMID- 9163058
TI  - [The use of trimetazidine in the combined therapy of postinfarct stenocardia].

PMID- 9163059
TI  - [Psychoemotional stress: its prevention and rehabilitation].

PMID- 9163060
TI  - [Calcium antagonists--the first-line preparations in modern cardiology (II)].

PMID- 9163061
TI  - [The postgraduate training of general practice physicians].

PMID- 9163062
TI  - [The work experience of the Department of Outpatient Therapy of the Saratov State
      Medical University].

PMID- 9163063
TI  - [The day hospital in the polyclinic--an efficient form of delivery of medical
      care to the population].

PMID- 9163064
TI  - Thrombin-inhibitor complexes in the blood during and after delivery.
AB  - Activation of coagulation leads to generation of thrombin which in turn is
      inactivated by the formation of thrombin-antithrombin (TAT) complexes, and
      thrombin-heparin cofactor complexes (T-HCII). These complexes were measured in
      plasma by ELISA methods. During normal delivery, the median TAT level in ten
      women increased from 4.1 to 7.8 times the median normal reference level. There
      was great individual variation, and levels 42 and 56 times normal median were
      found in two women shortly after normal delivery. The median T-HCII levels
      increased only moderately from 2.3 to 3.1 times median normal reference. D-dimer
      values were elevated in 28 out of the 30 samples. In blood sampled 1-2 days after
      delivery, the median TAT level was 2.5 times the median normal reference. The
      median T-HCII level was now 5.6 times the median normal reference value. The
      values were stable during the first 4 days post partum, and there was little
      difference between those delivered vaginally or by Caesarean section (C-section).
      D-dimer values were above normal reference in all women, and higher in women
      delivered by C-section. In conclusion, increasing TAT levels during labour and
      delivery indicated generation of thrombin which was mainly inactivated by
      antithrombin. The T-HCII levels increased less during delivery. In the early post
      partum period, the T-HCII levels were relatively more increased than the TAT
      levels. These results suggest that intravascularly generated thrombin is
      preferably inactivated by antithrombin, even in parturient women. In the post
      partum period, formation of T-HCII complexes was more evident, possibly
      reflecting extravascular inactivation of thrombin.

PMID- 9163065
TI  - Sphingosine-containing phospholipid vesicles support human factor VII
      autoactivation in the absence of tissue factor.
AB  - We studied the effects of lipid membrane composition on factor VII autoactivation
      and observed that factor VII was activated in the presence of phospholipid
      vesicles containing sphingosine. The time course for the factor VII activation
      was sigmoidal and the duration of the initial lag phase was decreased by the
      addition of exogenous factor VIIA. Kinetic studies revealed that factor VII
      activation in the presence of sphingosine-containing phospholipids can be defined
      by a second-order reaction mechanism with an apparent second-order rate constant
      of 1.1x10(4) M(-1)s(-1). The sphingosine-mediated factor VII autoactivation rate
      was dependent on the concentration of calcium ions and sphingosine content of the
      vesicles. Neither bovine serum albumin-conjugated sphingosine nor sphingosine
      analogues (ceramide, sphingomyelin) affected the factor VII autoactivation rate.

PMID- 9163066
TI  - Heterozygote for plasmin inhibitor deficiency developing hemorrhagic tendency
      with advancing age.
AB  - A heterozygote for congenital deficiency of plasma plasmin in inhibitor had
      hemorrhagic episodes repeatedly after the age of 79. Before the age of 79, he had
      not exhibited any hemorrhagic tendency and did not have abnormal bleeding even
      after surgical operations. Although heterozygotes for congenital deficiency of
      this inhibitor usually have no or only a mild hemorrhagic tendency, this case
      suggests that they may exhibit severe hemorrhagic tendency when they reach
      advanced ages because of age-related vascular changes producing hemostatic
      imbalance.

PMID- 9163067
TI  - Hemostatic abnormalities in inflammatory bowel disease.
AB  - Patients affected by inflammatory bowel disease (IBD) frequently suffer from
      thromboembolic events. Aims of this study were to investigate hemostatic system
      and the presence of antiphospholipid antibodies (aPL) in IBD patients. Forty-one
      patients affected by Crohn's disease (CD) and 19 by ulcerative colitis (UC) were
      studied, compared to 40 healthy control subjects. Platelet count (PLT), PT, aPTT,
      fibrinogen (Fib), prothrombin fragment F1+2, antithrombin (AT), protein C (PC),
      protein S (PS), factor XIII (FXIII), plasminogen (PLG), plasminogen activator
      inhibitor (PA1), spontaneous platelet aggregation in platelet-rich plasma (PRP
      SPA) and in whole blood (WB-SPA), and antiphospholipid antibodies (aPL) were
      evaluated. PLT, Fib, F1+2 and WB-SPA were significantly increased in IBD patients
      (p at least <0.05) both in active and inactive phases; aPL positivity was more
      frequent (p<0.05) and FXIII was significantly decreased (p<0.05) in comparison to
      control subjects. The thrombophilic state of IBD patients is not related to the
      degree of activity of the disease or to previous thrombotic events; aPL express
      the immunological alterations connected with IBD and are not the main cause of
      thrombotic events.

PMID- 9163068
TI  - Species specificity of anticoagulant activity of activated human protein C:
      involvement of factor V as well as protein S.
AB  - Activated protein C (APC) possesses species specificity in its anticoagulant
      activity. Human APC exerts only weak activity in rat plasma compared with that in
      human plasma. The present study was undertaken to estimate the difference in
      interaction of human and rat factors with human APC and to assess the cause of
      the species specificity. Human or rat protein S (PS), factor V, or factor VIII
      was used to supplement human plasma depleted of each respective factor, and the
      anticoagulant activity of human APC was measured in term of the elongation of
      activated partial thromboplastin time (APTT). The activity of human APC in rat PS
      or factor V-supplemented plasma was weaker than that in the human PS- or factor
      V-supplemented plasma. Furthermore, using purified human and rat factor V, human
      APC showed weaker inactivation of rat factor V than human factor V. Equal
      anticoagulant activity was observed in human or rat factor VIII-supplemented
      plasma. And there was a little difference in the interaction of APC with its
      inhibitors in human or rat plasma during a few minutes of incubation as judged by
      measurement of residual activity by an enzyme capture assay. From these results
      factor V as well as PS seems to play a major role in the species specificity of
      APC.

PMID- 9163069
TI  - Decreased erythrocyte deformability in glycogen storage disease.
AB  - Liver glycogen storage diseases (GSD) are disorders associated with severe
      dyslipidaemia which can induce cell membrane alterations and possibly reduced
      cell deformability. Since decreased erythrocyte deformability is known to disturb
      blood flow in capillaries and may promote ischaemic diseases, this study was
      designed to investigate erythrocyte deformability using a new filtration system,
      the Cell Transit Analyser (CTA), and to examine lipid compounds in the blood of
      23 patients affected with GSD, aged from 1 to 20 years and 18 controls aged from
      1 to 17 years. The patients showed a mixed hyperlipidaemia with predominant
      hypertriglyceridaemia and an increase in erythrocytes mean transit times (TT) due
      to the presence of more rigid erythrocytes subpopulations when compared to
      controls. Thus the erythrocyte rigidity, in addition to the lipid abnormalities
      must be taken into account for long-term evolution of GSD patients. Moreover this
      cellular alteration may contribute to shortened erythrocyte survival.

PMID- 9163070
TI  - D-dimer specific monoclonal antibodies react with fibrinogen aggregates.
AB  - Human fibrinogen exposed to 46.5 degrees C was subjected to gel permeation
      chromatography. The protein eluted in two distinct peaks. The first peak appeared
      in the void volume containing soluble fibrinogen aggregates, while the other peak
      represented monomeric fibrinogen. In contrast to the monomeric peak material, the
      aggregate fraction reacted with a panel of monoclonal antibodies specific for
      fragment D-dimer using an ELISA system. Edman degradation showed that both the
      aggregate and the monomeric fractions were devoid of soluble fibrin, and
      immunoblots of SDS-PAG electrophoretic profiles disclosed no sign of stabilized
      high molecular weight derivatives. We have previously shown that the aggregate
      fraction of similarly treated fibrinogen, in contrast to the monomeric fraction,
      stimulates the t-PA catalyzed conversion of plasminogen to plasmin and
      concomitantly exposes the sequences Aalpha-(148-160) and gamma-(312-324) involved
      in t-PA stimulation. Our present and previous findings suggest that soluble
      fibrinogen aggregates possess a fibrin-like structure, and that fibrin or
      fibrinogen polymer formation is a prerequisite for the enhancing effect on t-PA
      mediated plasminogen to plasmin conversion which is seen even with the polymers
      in the soluble state.

PMID- 9163071
TI  - D-dimers are degraded by human neutrophil elastase.
AB  - To see if D-dimers were degraded by human neutrophil elastase (HNE), cross-linked
      fibrin was obtained by adding thrombin to purified fibrinogen in the presence of
      calcium ions and factor XIII, and the fibrin clot subsequently degraded by
      plasmin. Thereafter, the supernatant containing fibrin degradation products was
      removed and incubated with HNE. D-dimer levels were measured by two rapid
      semiquantitative tests, a latex agglutination test and the Nycocard
      immunofiltration test, and a quantitative ELISA-method. With increasing
      incubation time, D-dimer levels as measured by the latex and Nycocard tests
      rapidly decreased and subsequently became undetectable, while the ELISA D-dimer
      values remained essentially unchanged. By using SDS-electrophoresis and
      immunoblotting, the degradation of plasmic derivatives of cross-linked fibrin by
      fiNE was visualised. We conclude that in a purified system, D-dimers formed
      during plasmin mediated lysis of cross linked fibrin are further degraded by HNE.
      Such HNE degradation reduces the D-dimer concentration as measured by rapid
      semiquantitive tests, and may be partly responsible for discrepant results when
      using different D-dimer assays.

PMID- 9163072
TI  - Comparative intravenous antithrombotic actions of heparin and site directed
      thrombin inhibitors in a jugular vein clamping model.

PMID- 9163073
TI  - Direct PCR of leukocytes treated with microwave irradiation to detect factor V
      Leiden mutation.

PMID- 9163074
TI  - Short-time stability of markers of coagulation and fibrinolysis in frozen plasma.
      [correction].

PMID- 9163075
TI  - [Professional standards].

PMID- 9163076
TI  - [The status and outlook in the prevention and treatment of suppurative
      inflammatory diseases of the maxillofacial area].

PMID- 9163077
TI  - [A new approach to the description of the anatomical characteristics of the
      surfaces of human teeth].
AB  - A new approach to the anatomical structure peculiarities description of the crown
      part of the tooth surface by the system of the parallel sections is suggested. It
      helps to make their graphic picture and analytical description producing a new
      anthropometric system of assessing normal and pathological conditions.

PMID- 9163078
TI  - [The effect of noncoherent infrared radiation on the bone tissue reparation of
      the mandible in an experiment].
AB  - Exposure of rabbits with mandibular bone defects to coherent infrared radiation
      (IR) at a wavelength of 890 nm decreased the intensity of inflammation by
      accelerating the repair. The results of exposure of the injured site to
      noncoherent IR radiation are compatible with those of IR laser exposure.

PMID- 9163079
TI  - [The comparative characteristics of the antibacterial activity of new antiseptics
      and the prospects for their use in dental practice].
AB  - Antibacterial activities of modern antiseptics listerine, myramistine, cidipol,
      octenisept, tantum verde, matecide, and rautine drugs chlorhexidine and dioxidine
      are compared. The prospects of their use in dentistry for the treatment of
      inflammations associated with anaerobes are discussed. Metacide, listerine,
      chlorhexidine, and dioxidine are characterized by the widest spectrum of activity
      towards obligate anaerobic bacteria; moreover, these drugs inhibit bacterial
      growth when used in lower concentrations than other drugs.

PMID- 9163080
TI  - [The combined treatment of lichen ruber planus of the mouth mucosa].
AB  - The treatment of 53 patients with lichen planus of the buccal mucosa included
      common methods of detoxication and immunomodulators in order to normalize the
      immune status and was supplemented with applications of codfish oil enriched with
      polyunsaturated fatty acids. As a result of such treatment, the duration of
      exacerbation was shorter and a stable more than one-year remission was attained,
      associated with normalization of the immunological parameters. In patients with
      the erosive ulcerative form of lichen local applications of codfish oil and
      gargling with Potentilla tormentilla tincture were conducive to a sooner control
      of the process.

PMID- 9163081
TI  - [The effect of endogenous intoxication on liver function in patients with
      phlegmons of the face and neck].
AB  - The function of the liver is assessed in patients with maxillofacial phlegmons
      suffering from endogenic intoxication of different severity. The most marked
      changes of the enzymatic activity of the liver were observed in patients with
      progressive phlegmons and complications thereof (mediastinitis or sepsis)
      involving endotoxicosis of the second or third degree. The authors come to a
      conclusion on the functional hepatic failure in patients with phlegmons of the
      face and neck, which fact should be borne in mind when planning combined therapy
      of this patient population.

PMID- 9163082
TI  - [The treatment of patients with comminuted fractures of the bones of the
      zygomatico-orbital complex].
AB  - The paper presents a new method for fixing bone fragments and the entire
      zygomatic bone in patients with comminuted fractures of the zygomatico-orbital
      complex. Demonstrates the possibility of repair of the zygomatic bone and the
      contours of the zygomatico-orbital area. Discusses the probability of venous
      inclusion in the treatment of patients with posttraumatic deformations of the
      upper and median zones of the face. Stable cosmetic and functional results were
      attained in 12 patients treated by this method.

PMID- 9163083
TI  - [The functional state of the muscles of the maxillofacial area during immediate
      denture placement].
AB  - Electromyographic studies demonstrated that immediate dentures ensure full-value
      repair of the functions of the masticatory, temporal, and suprahyoid muscles. Six
      months after fitting with dentures the coordination of antagonist and synergist
      muscles was impaired in but 18% of patients. The author emphasizes that immediate
      dentures are the most rational and pathogenetically valid orthodontic treatment
      preventing maxillodental deformations.

PMID- 9163084
TI  - [The dental service of Russia and the outlook for its development under the new
      economic management conditions].

PMID- 9163085
TI  - [Periodontal tissue status in shortening of the interalveolar distance].
AB  - A total of 186 patients aged 40 to 65 with short interalveolar distance were
      treated. 65.5% of them developed pathological changes in the marginal periodontal
      tissues (inflammation, periodontal and osseous pouches, resorption of bone tissue
      of the maxillary alveolar process). Patients with involvement of the marginal
      periodontal tissue were treated by therapeutic, surgical, and orthodontic
      methods. Good results were attained in 95.1% of patients.

PMID- 9163086
TI  - [The results of epidemiological studies of dental caries in children of the
      Siberian region].
AB  - Thorough epidemiologic studies are the basis for the development of effective
      methods and means of primary prevention of dental caries in children. With this
      aim in view, we examined 21,035 children living in various rural and urban
      regions of west Siberia. The duration of their stay in the Extreme North was
      taken account of, as well as levels of fluoride, selenium, and other odontotropic
      substances in drinking water and other biogeographical factors over the recent
      one or two decades. The study demonstrated an increasing incidence and intensity
      of caries, particularly so in the rural regions, which is due to insufficient
      primary and secondary prophylactic measures. The highest incidence and intensity
      of the disease were observed in the residents of Tyumen Province. For improving
      the prevention of dental diseases it is necessary that epidemiological factors in
      the studied regions be taken into consideration.

PMID- 9163087
TI  - [A method for assessing the morphological status of the maxillodental system].
AB  - The authors propose a device for measuring plaster models of patients' jaws with
      normal occlusion in order to evaluate the distance from the coordinate point to
      the point between the incisors (i), points of contact of the canines (p) and of
      contact of the first molars of the maxilla and mandible (m). It is possible to
      assess the position of the upper and lower dentition in the skull space in
      relation to the universal parameter--the coordinate point common for both
      dentitions and parameters of the skull.

PMID- 9163088
TI  - [The differential diagnosis of lymphangiomas of the maxillofacial area in
      children based on echographic data].

PMID- 9163089
TI  - [Intellectual property under the conditions of market relationships and insurance
      medicine].

PMID- 9163090
TI  - [Full partnership in dentistry].

PMID- 9163091
TI  - [The problems of the postgraduate training of dentists].

PMID- 9163092
TI  - [The small dental practice enterprise in Germany].

PMID- 9163093
TI  - [The significance of the microflora of the oral cavity in the etiology and
      pathogenesis of lichen ruber planus].

PMID- 9163094
TI  - [The 75th anniversary of the N. A. Semashko Moscow Medical Stomatology
      Institute].

PMID- 9163095
TI  - [The status of research in dentistry].
AB  - Discusses the problems of market relationships in Russian dentistry and insurance
      medicine: various forms of intellectual property, the market of equipment and
      materials for dentistry, such forms as lease contract or working place lease. The
      authors emphasize the contribution of the intellectual potential to the
      development of novel equipment and materials and clinical methods.

PMID- 9163096
TI  - Proceedings of the 2nd International Symposium on Molecular Steroidogenesis.
      Monterey, California, June 7-11, 1996.

PMID- 9163098
TI  - [The effect of spermatozoon morphology on the fertilization rate and on disorders
      in early embryonic development].
AB  - The influence of teratozoospermia on the results of in vitro fertilization was
      analysed. Indices of normal sperm morphology, in cases of failed fertilization in
      vitro, significantly differ from those of successful fertilization. Fertilization
      rate in patients with less than 14.0% of normal sperm morphology was 41.9%. If
      the index of normal sperm morphology exceeded 14.0%, the rate of fertilization
      made up 62.2%. These data enable us to conclude that teratozoospermia may result
      in zygote development disorders and in the increased probability of embryo
      fragmentation.

PMID- 9163097
TI  - [Hydrogen peroxide as a signal molecule].
AB  - This review deals with numerous literature data on the action of small redox
      active H2O2 biomolecule on the cellular activity. Evidence is provided on H2O2
      sources in the cell, intracellular antioxidants and scavengers, and on the
      dependence of cellular response (cell damage or activation) on H2O2
      concentration. Stimulation of cells by nontoxic doses of H2O2 and possible
      activation mechanisms are also discussed. The number of examples is given
      demonstrating H2O2 playing the role of a second messenger for the variety of
      agents that stimulate the cells.

PMID- 9163099
TI  - [The structure of Alu-like DNA nucleotide sequences in cyclostomes and fishes].
AB  - By methods of DOT hybridization and polymerase chain reaction (PCR) structures
      similar to Alu repeats were shown in the genome of fish and lamprey. The fact of
      the presence of such sections in representatives of many orders of fishes, and
      also our experimental data allow to suppose that Alu-like structures, similar to
      3' region of Alu repeats on mammals, have been already formed in these. The
      evolutionary significance of described structures has been supposed.

PMID- 9163100
TI  - [The effect of the increase in the calcium concentration induced by action of the
      ionophore A-23187 on mitosis in cultured ESK cells].
AB  - After addition of 20 mM calcium ionophore A23187 to cultured PK (pig kidney
      embryo) cells, [Ca++] in cytosol increased by more than 10 times. The maximum
      [Ca++] concentration was observed 1-2 min after drug introduction. Later on
      [Ca++] gradually decreased, and after 30 min of incubation with A23187 [Ca++] its
      concentration was 3-5 times higher than in the norm. 1 min after introduction of
      the calcium ionophore, mitotic spindles shortened for 1/3 and the angle of
      divergence of spindle microtubules from the centrosome extended. These changes
      remained for 5 min of treatment. After nocodazole treatment the length of the
      mitotic spindle reduced (2 min), then mitotic spindle and the metaphase plate
      were disrupted. The rate of mitotic spindle shortening after addition of the
      ionophore is about the same as after addition of nocodazole, but after ionophore
      treatment the metaphase plate remained for more than 5 min. Based on the results
      obtained we suggest that the maximum distance between spindle poles at metaphase
      is in the intact cell, and after any perturbation of normal microtubule dynamics
      the spindle may rapidly collapse. The collapsed mitotic spindle becomes more
      stable and its size is determined predominantly by kinetochore fibers. The
      metaphase spindle is completely and rapidly destroyed when the microtubule growth
      is prohibited, but it is preserved when this growth is restricted.

PMID- 9163101
TI  - [The dependence of the osmotic properties of Escherichia coli bacteria on
      temperature].
AB  - The influence of water solutions of NaCl on the osmoresistance and reproduction
      of E. coli B/r and E. coli Bs-1 at different temperatures was studied. The
      increase in cell resistance was studied. The increase in cell resistance to NaCl
      hypertonia was noticed after the temperature rise from 20 to 37 degrees C. In
      this case the concentration of NaCl in the medium, which made this medium
      isotonic, was seen to increase too. On the contrary, when the temperature
      decreased to 0 degrees, the cell resistance to high concentrations of NaCl was
      found suppressed. In this case the concentration of NaCl in the medium, which
      made this medium isotonic, was seen to decrease. The salt tolerance of bacteria
      reproduction was found to depend on the temperature: the tolerance increased with
      the temperature rise, and vice versa. It is concluded that the solution
      temperature was to be considered as one of the major factors governing the
      osmotic bacterial cell homeostasis.

PMID- 9163102
TI  - [An immunohistochemical study of the expression of transcription factor Oct3/4 in
      mouse spermatogenesis].
AB  - The expression of POU-domain transcription factor Oct3/4 in the testis of adult
      mice has been studied using indirect immunofluorescence with highly specific
      antibodies. The protein is shown to be expressed in germ cells of seminiferous
      epithelium in a stage specific manner. The protein synthesis is initiated in mid
      pachytene spermatocytes, increases to reach its peak during meiotic division. The
      Oct3/4 level remains augmented in early spermatids, but gradually declines during
      their further developmental advancement. These findings imply that Oct3/4 may
      have a regulatory function providing for the control of meiosis and/or terminal
      differentiation of spermatogenic cells.

PMID- 9163103
TI  - [The effect of the tumor suppressor p53 and its mutant forms on the
      differentiation and viability of K562 leukemic cells].
AB  - Mutations of the p53 tumor suppressor are often observed in various human
      malignancies including blast crisis of chronic myelogenous leukaemia (CML). The
      pattern of p53 mutation in CML shows some peculiarities as compared with the
      majority of other neoplasias. In particular, the substitutions at codon 273, one
      of the most common p53 alteration in various tumors, are not characteristic of
      CML. To test whether distinction in the pattern of p53 mutation are associated
      with certain peculiarities of biological effects of different mutant proteins in
      myeloid cells, we obtained and analysed a panel of human K562 cell sublines
      expressing various exogenous p53: human Pro156, His175, His194, Trp248 and His
      273, or murine temperature-sensitive (ts) Val135 that has properties of mutant
      protein at 37 degrees C, but shows activities of wild-type (wt) p53 at 32 degrees
      C. We have found that expression of wt-p53 enhanced the dependence of cells on
      growth/survival factors, incubation of sparse (< 10(5) cells per/ml) K562/Val135
      cultures at 32 degrees C caused apoptosis. In media conditioned by cells of
      different origin (K562, colorectal carcinoma LIM 1215, Rat1 fibroblast) the p53
      dependent apoptosis was inhibited. In conditions that do not lead to apoptosis,
      the expression of ts-wt-p53 was accompanied by dramatic increase in the number of
      cells containing glycophorin A (GlycPhA) and "antigen of erythroblasts"--specific
      markers of erythroid differentiation. Unlike the wt-p53, the majority of tumor
      derived mutant p53 (Pro156, His175, His194, Trp248) increased cells survival in
      media with low serum content and decreased the number of cell expressing GlycPhA,
      CD9, CD15 and CD71 differentiation antigens. On the other hand, expression of
      His273-p53 caused a significant augmentation in the number of CD9-positive cells
      and enhanced the dependence on growth/survival factors that are present in serum
      or conditioned media. The data obtained are consistent with the idea that unusual
      pattern of p53 mutations in CML can reflect the peculiarities of the effects of
      some mutant proteins on differentiation and/or viability of leukemic cells.

PMID- 9163105
TI  - [A micromanipulator for the microscope photometer].
AB  - A micromanipulator is described to be designed for micro-operations on cells and
      for various cytological investigations using microelectrodes especially when cell
      scanning with inserted microinstrument is required. The baseplate of positioners
      is a light plate located on the microscope stage immediately. Thus, it is
      possible to do the following operations: to move the object in the field of
      vision of the microscope simultaneously with the inserted instrument; to insert
      several microinstruments into one cell; to make photometry of the cell with the
      inserted instrument by the scanning method. The positioners bear mechanical
      micromanipulator which ensures the moving of the instrument in three coordinates
      (8 mm lengthwise, 3 mm crosswise, and 4 mm in upright position). The
      micromanipulator can be employed with any type of biological microscopes and
      makes it possible to use objectives of high magnification (up to 100x). A little
      weight of the instrument (1 kg) makes it convenient to be used in the expedition.

PMID- 9163104
TI  - [The dual function of the proliferating cell nuclear antigen (PCNA) in the
      response of human cells to UV damages].
AB  - An auxiliary protein of DNA polymerases delta and epsilon, the proliferating cell
      nuclear antigen (PCNA), is necessary for efficient DNA replication in vivo and in
      vitro, and also for the repair synthesis in vitro, but its role in the excision
      repair of genome in vivo is not exactly established. In S-phase of unirradiated
      cells, PCNA is tightly bound to focal centers of DNA replication and is not
      removed by treatment with detergent Triton X-100, but is completely extracted
      from non-S-phase cells by the indicated detergent. It was shown earlier that
      after UV-irradiation PCNA could not be removed by the detergent even from non-S
      phase cells. It was interpreted as the evidence of PCNA integration into the
      repair complex and of the participation of this protein in repair synthesis in
      vivo. In the present work the data were obtained indicating that the role of PCNA
      in cell response to UV-damage was not confined only to its possible involvement
      in repair synthesis. With the help of confocal microscopy it was established that
      in Triton X-100-extracted normal cells PCNA did not colocalize with the well
      known excision repair protein XPB/ERCC3, defective in cells from Xeroderma
      pigmentosum (complementation group B) patients. XPB-protein is induced by UV
      irradiation in normal cells, and this induction is not observed in repair
      deficient cells. However, in such cells UV-light induces a detergent-resistant
      form of PCNA, and this form is obviously not connected with repair. It cannot be
      excluded that a rapid PCNA immobilization immediately after UV-irradiation of
      cells is needed for the facilitation of photochemical damage bypass during the
      subsequent replication of genome.

PMID- 9163106
TI  - [A flow chamber for the intravital cytophotometry (microscopy) of muscle and
      nerve fibers and for the intracellular microelectrode lead take-off of
      biopotentials].
AB  - A chamber is described with permanent solution flux aimed for in vivo
      cytophotometry (microscopy) of the nerve and muscle fibres, and for
      microelectrode registration of biopotential. Little size and construction
      peculiarities of the chamber make it possible to use objectives of middle and
      high magnification and to insert a microinstrument into the fiber.

PMID- 9163107
TI  - [Prescription of morphine].

PMID- 9163108
TI  - [Tobacco smoking. What happened since 1971?].

PMID- 9163109
TI  - [SPECT and PET in neurobiology].

PMID- 9163110
TI  - [Strategies for investigating non-assimilation. A critical status].
AB  - This review reevaluates the rational basis for choice of diagnostic strategies in
      patients with suspected malassimilation. Prospective evaluation of diagnostic
      tests must fulfil several requirements for a correct assessment of their clinical
      value. Very few studies meet such requirements, resulting in unnecessary
      investigations as well as overlooked cases with a negative impact on patients and
      society. This problem includes evaluation of assimilation of macronutrients
      (carbohydrate, fat, protein) as well as micronutrients (e.g. vitamin B12), and it
      is further complicated by the occurrence of conditions with occult (compensated)
      malassimilation. Malassimilation of carbohydrates may be physiological (starch,
      fructose, sugar alcohols etc., in certain ethnic groups lactose) as well as
      pathological. In both instances chronic gastro-intestinal distress may arise in
      sensitive individuals. The diagnosis is based on tolerance tests, combined with
      blood tests or breath tests (hydrogen excretion). The latter is considered the
      most reliable, but the available evidence for choice of tests is not solid.
      Similar reservations apply to conditions of bacterial overgrowth of the small
      intestine, which may lead to diffuse malassimilation. The frequency and clinical
      importance of this condition is in all probability underestimated. Screening for
      coeliac disease may be achieved by several serological tests (reticulin-, gliadin
      , endomysial antibodies), of which IgA-endomysial antibodies seem superior.
      Comparative studies are often flawed in design, however, and permeability tests
      may also eventually find their place in the test battery. There is thus a strong
      need for more evidence-based diagnostic strategies in patients with suspected
      malassimilation.

PMID- 9163112
TI  - [Who dies of morphine and dextropropoxyphene intoxication? Danish experiences
      from the period 1979-1992].
AB  - We studied deaths following intoxication with dextropropoxyphene (D) and opioids
      (M) in Denmark 1979-1992 with special reference to the sex, age group,
      contributory cause of death (secondary diagnosis) and manner of death. Deaths
      following D increased until 1985 for both sexes, where a total of 46 women and 64
      men died. In 1985 the National Board of Health drew public attention to this
      problem which led to a decrease in these deaths among men, while in women a
      paradoxical increase in suicides outnumbered a reduction in deaths from
      intoxication accidents. In 1988 D was assigned to the more restrictive
      prescription rules of opioids, which further reduced the number of deaths. The
      reduction of D deaths was followed by a corresponding increase in deaths due to
      M. However, the demographic characteristics of D and M deaths were not entirely
      identical: The typical D victim had a history of psychiatric disease or
      drug/alcohol abuse and committed suicide; the age was 40-59 for women and 20-39
      for men. The typical M victim also had a history of psychiatric disease and
      substance abuse but suicides were less common and the majority occurred in the
      age group 20-39 in both sexes. Both D and M deaths were rare in persons with a
      somatic secondary diagnosis. We conclude that these poisonings warrant continued
      attention, and that a more restrictive prescription practice of D and M to
      patients at risk is justified.

PMID- 9163111
TI  - [Malignant bone pain].
AB  - Bone pain is one of the most frequent causes of pain in patients with cancer, and
      the levels of metastases and bone pain are not directly correlated. Nociceptors
      in the periosteum are probably stimulated by halisteresis or by inflammatory
      oedema leading to an increase in the intraosseous pressure. Some authors believe
      that the nociceptors in bone are mediated via intraosseous mechanoreceptors in
      the bone-matrix. At a low pain level the initial treatment is acetylsalicylic
      acid, paracetamol or other nonsteroidal antiinflammatory drugs. At increasing
      pain level initial doses of oral opioids are added. In severe bone pain, where
      conventional therapy seems difficult, opioids are administered by invasive
      techniques. In localised bone pain palliative radiation is the first treatment of
      choice. Corticosteroids induce an analgetic effect indirectly by reducing the
      inflammatory oedema, inhibiting the synthesis of prostaglandins and may inhibit
      excitatory nerve fibres. Endocrine treatment, calcitonin and biophosphonates have
      shown a documented pain-relieving effect in patients with disseminated breast and
      prostate cancer. Chemotherapy has shown a pain-relieving effect in patients with
      disseminated breast cancer, surgical intervention is used in stabilizing
      osteolytic bones before or after a fracture ensuring a reasonable relief of pain.

PMID- 9163113
TI  - [Use of on-call service by patients with pain in the county of Aarhus].
AB  - The aim of the study was to describe the numbers and other characteristics of
      patients who contacted the general practitioners (GP) out-of-hours on-call
      service with pain as the most important or major contributing reason for the
      contact. Data were collected from a questionnaire entered in the GPs' computer
      system. About 80% of the GPs participated. Over a 14 day period 10,653 contacts
      were registered, and of these 4718 were analyzed, consisting of 2080 telephone
      consultations, 1316 consultations and 1322 home visits. The results showed that
      30% of the telephone calls, 37% of the consultations and 41% of the home visits
      concerned a patient with pain problems. Of these contacts concerning pain
      patients, the physicians estimated that 33% of the consultations and home visits
      and 55% of the telephone calls were "less necessary" or "unnecessary". It is
      concluded that pain is a major reason for contacting the GPs' on-call service,
      and that physicians deem many of these contacts "less necessary" of
      "unnecessary". Better information to citizens and better education of the
      physicians might enable some of these contacts to be transferred to normal
      working hours.

PMID- 9163114
TI  - [Prescription of strong analgesics in the out-of-hours general practice in the
      county of Aarhus].
AB  - The article describes the ordination of opioid analgesics in the out-of-hours
      general practice service to patients with pain due to an illness lasting for more
      than two days. The physicians working out-of-hours duty and the patient's GP
      answered a questionnaire. The research includes 227 contacts. The results showed
      that the main diagnoses were: migraine/headache (33%), angina pectoris (19%) and
      back-pain (11%). The physicians estimated 33% of the contacts to be "less
      necessary" or "unnecessary". In 78% of the cases the GPs "agreed" or "almost
      agreed" with the deputizing doctors' use of opioids. In most of the cases the
      patients' usual GPs agreed with the treatment prescribed by the deputizing
      doctors. There seems to be a disagreement between the GPs and the Danish National
      Board of Health about the principles concerning the use of opioids.

PMID- 9163115
TI  - [Total parathyroidectomy and autotransplantation of parathyroid tissue.
      Functional assessment of the autograft 5-10 years after surgery with the help of
      local ischemic blockade].
AB  - The aim of the present study was to assess the long-term function of
      autotransplanted parathyroid tissue. From the medical records of a consecutive
      series of 21 patients we found that during the time of follow-up (79 months) one
      patient developed parathyroid graft dependent recurrent hyperparathyroidism (HPT)
      and one patient suffered from hypoparathyroidism. Nine of the patients were
      available for measurements of the plasma concentrations of intact parathyroid
      hormone (iPTH) at rest and during a shortlasting ischaemic blockade of the
      autotransplant. In eight patients, the ischaemic blockade reduced the
      concentration of iPTH with on average 62% as compared to baseline values. In one
      patient, the autotransplant had been resected and as expected, iPTH did not
      change during ischaemic blockade. Our results indicate that total
      parathyroidectomy with autotransplantation provides a rational alternative to the
      surgical treatment of secondary HPT and that the ischaemic blockade manoeuvre
      seems suitable for assessment of the function of parathyroid autotransplants.

PMID- 9163116
TI  - [Penicillin treatment of non-nosocomial pneumonia in Danish medical departments.
      A questionnaire].
AB  - This study describes the most common penicillin-regime for hospitalized patients
      with community-acquired pneumonia in Denmark. One hundred and seventy-one
      consultant physicians received an anonymous questionnaire, 85% were returned and
      75% were evaluated. The most common regime is a treatment duration of six to ten
      days with 3-6 million IU of penicillin daily given in three doses. The most
      common route of administration is intravenously until the patient's body
      temperature drops. Then the same dose is given orally. Variations in strategy
      were revealed and call for further investigations to establish and maintain
      restrictive antibiotic regimes.

PMID- 9163117
TI  - [Medication errors in a pediatric department].
AB  - In a prospective study, iatrogenic medication errors were registered among
      paediatric admissions. The two most common causes of incidents were neglecting to
      give a medication on schedule and administration of an incorrect dose-but extra
      dose errors, errors of omission, wrong rate errors and administration of
      unauthorized drugs also occurred. After implementation of a satellite pharmacy,
      medication error rates were compared, and a reduction of the more serious and
      potentially harmful incidents was shown.

PMID- 9163118
TI  - [Toxic shock-like syndrome caused by streptococci--treated with clindamycin].
AB  - The number of invasive group A streptococcal infections have been increasing in
      the last years. Toxic Shock-like Syndrome due to infections with streptococci
      (TSLS) is a serious condition still associated with a mortality rate of 30%
      despite proper treatment. Early diagnosis is difficult and early treatment is
      important. A typical case of TSLS in a previously healthy 33 year-old woman
      treated with clindamycin is reported. Penicillin is still the drug of choice for
      most Group A streptococcal infections, but in fulminant infections failure has
      been described. Clindamycin is a good choice in complicated infections.

PMID- 9163119
TI  - [Evidence-based health care].

PMID- 9163120
TI  - [Malaria prevention].

PMID- 9163121
TI  - [Characteristics of destructive changes in the middle ear of patients with
      chronic otitis media, purulent complicated by local pachymeningitis].
AB  - The author made a comparison of clinical and morphological examinations of 150
      patients with otitis media purulenta chronica. Being an initial stage of otogenic
      intracranial complications, local pachymeningitis is characterized by more
      pronounced destruction of the temporal bone. In emergence of local
      pachymeningitis signs an urgent operation on the middle ear is needed.

PMID- 9163122
TI  - [Outcomes of heterobrephomastoidoplasty in surgical treatment of chronic otitis
      media purulent in children].
AB  - Otitis media purulenta chronica (OMPC) in children affects frequently the mastoid
      process necessitating plastic repair of the mastoid cavity. Taking this in
      consideration, in the surgery of 66 children with OMPC the authors used implants
      of demineralized lamb bone tissue. The graft retention occurred in 93.9% of
      cases.

PMID- 9163123
TI  - [Some anatomical features of the long process of the incus].
AB  - Investigation of a series of histological sections of 40 auditory bones showed
      the existence of a dense partially developed connective tissue between the long
      process of the incus and the lenticular process. This indicates that the
      lenticular process is a separate bone--the least in the body (weight--0.12-0.20
      mg, diameter--0.5-0.8 mm).

PMID- 9163124
TI  - [Pharyngeal scars stenosis in children].
AB  - The treatment and follow-up data are available for 18 children (12 boys and 6
      girls) with persistent scarry pharyngostenosis. The disease was first diagnosed
      at the age of 1 year 8 months to 12 years. Pharyngostenosis has resulted from
      burn induced by KMnO4 crystals. After treatment (laser destruction in 13 patients
      and bourginage in 4 patients) 15 patients resumed free breathing. 2 patients
      continue the treatment.

PMID- 9163126
TI  - [Treatment of acute sinusitis using sinus catheter IaMIK-3].
AB  - Potentialities of a new design of sinus-catheter YMIK-3 are considered in the
      treatment of 68 patients with acute sinusitis. Essential details of the procedure
      are described. A mechanism of action of controlled pressure on nasal mucosa edema
      is specified. The use of YMIK-3 catheter has the advantage of reduced duration of
      the procedure, low traumaticity for patients, wide adjustment range for the
      patient's size. In the block of the sinus shunt the delayed procedure is
      recommended.

PMID- 9163125
TI  - [Laryngeal and other organs neoplasms multiple primary].
AB  - The authors present follow-up data on 227 patients with laryngeal cancer. All the
      patients have received radical treatment. Long- and short-term responses are
      analyzed with special emphasis on patients with multifocal lesions (12 patients
      with cancer of the larynx and other organs).

PMID- 9163127
TI  - [Potentialities of contrast angiography and endovascular embolization in ent
      bleeding].

PMID- 9163128
TI  - [Nose bleed and current methods of their management].
AB  - The authors analyze statistical data on nasal haemorrhages in 50 patients
      regarding haemorrhage etiology and hospital stay. Treatment results are available
      for patients with recurrent nasal haemorrhages and essential hypertension. The
      patients have undergone submucosal resection of the nasal septum. The technique
      of this operation with reimplantation of the autoligament and autobone is
      detailed. The procedure proved highly effective in management of recurrent nasal
      haemorrhages.

PMID- 9163129
TI  - [Life threatening hemorrhage in emergency otorhinolaryngological care].
AB  - The authors report 6 cases of life threatening hemorrhage which occurred in 1985
      1995. The cases were characterized by massive recurrent bleeding resistant to
      standard conservative methods of stopping. In a posttonsillectomy patient
      bleeding from the tonsillar niche and in two patients nasal bleeding because of
      trauma or tumor were stopped only after ligation of the external carotid artery.
      Arrosive bleeding from the internal jugular vein in a patient after opening of a
      deep tonsillogenic neck flegmon was stopped by ligation of the jugular vein along
      the length of the wound. Bleeding after opening of a paratonsillar abscess was
      stopped after abscess tonsillectomy. Bleeding from tracheostoma was stopped only
      after suturing of the vessel in the wound. All the 6 patients were discharged in
      a satisfactory condition.

PMID- 9163130
TI  - [Ligenten treatment of sinusitis].
AB  - Efficacy of local treatment with ligenten which was introduced after irrigation
      of the nasal sinuses was tried versus control intranasal introduction of 1%
      dioxidin solution. 35 and 25 patients with acute sinusitis or aggravation of
      chronic purulent sinusitis were treated, respectively. Subjective and objective
      responses in the study and control groups assessed with the use of sensor
      analogue and visual-analogue scale demonstrated higher efficacy of ligenten.

PMID- 9163131
TI  - [Foreign bodies of the ear].
AB  - The paper presents practical aspects of diagnosis and management of foreign
      bodies found in the ear. Methodological approaches of medical aid to patients
      with foreign bodies in the ear are described. It is shown that such foreign
      bodies can provoke severe complications. The authors have developed a convenient
      classification which enables valid assessment of the clinical situation and
      facilitates a choice of the adequate therapeutic policy.

PMID- 9163132
TI  - [20-year experience in obliteration of the frontal sinuses with formalinized
      allobrephobone in chronic frontal sinusitis].
AB  - Outcomes of surgical treatment of chronic recurrent frontal sinusis (FS) using
      obliteration of the frontal sinuses with allobrephobone in 228 patients (190
      males and 38 females aged 15-71 years) are presented. 45 of them had undergone
      surgery on the frontal sinuses with reestablishment of the frontonasal shunt.
      Obliteration consists in removal granulations and polyps from the frontal sinus
      through the anterior wall followed by sinus mucosa scraching and the sinus
      separation from the nasal cavity with filling with small pieces of formalized
      allobrephobone. The technique is simple, postoperative period usually uneventful.

PMID- 9163133
TI  - [Method of plastic replacement of extended laryngopharyngeal and cervical
      esophagus defects ].
AB  - Filling of extended pharyngoesophagostomas were made in 13 patients operated for
      advanced laryngeal cancer by means of microsurgical autotransplantation by the
      forearm radial flap. The latter was created in the form of two cutaneous elements
      on common fascial base. After transfer of the autotransplant in the recipient's
      bed, one cutaneous element filled the defect of the laryngopharyngeal and
      esophageal inner coating, the second filled the defect of the outer coating. This
      method is reliable, effective, low traumatic, helps to avoid abdominal surgery.

PMID- 9163134
TI  - [Critical assessment of external surgery of frontal sinuses with shunting].

PMID- 9163136
TI  - [Thrombophlebitis of external jugular vein of tonsillogenic origin].

PMID- 9163135
TI  - [Clinical features of Wegener disease].

PMID- 9163137
TI  - [A case of subfold laryngitis as a complication of diphtheria vaccination].

PMID- 9163138
TI  - [A case of stab-incised wound of neck with involvement of the vascular bundle].

PMID- 9163139
TI  - [Reiter's disease manifestations on oral and pharyngeal mucosa].

PMID- 9163141
TI  - [Atypical thrombosis of venous collectors of posterior cranial fossa as a
      complication of chronic otitis media, purulent].

PMID- 9163140
TI  - [Otogenic abscess of temporal lobe breaking into the lateral ventricle of brain
      with good outcome].

PMID- 9163142
TI  - [Foreign bodies of the ear, pharynx and esophagus].

PMID- 9163143
TI  - [Problems of hearing loss in aviation engineers (professional and ecological
      aspects)].
AB  - Health standards for noise were exceeded 3 times when noise characteristics were
      measured at jobs and in apartments of engineers engaged in maintenance of modern
      aircraft. These specialists were exposed to noise in working hours and at night.
      Audiometry registered hearing problems in 69% of the examinees. 20% of them had
      hearing loss of the second degree. In engineers living closer to airports hearing
      was damaged more seriously, especially at frequencies 1000-8000 Hz. This fact
      demonstrates ecological implication of non-occupational acoustic load. Relevant
      regression levels were derived from correlation of noise doses with tonal
      hearing. Natural and experimental investigations proved efficacy of
      impedancemetry in objective assessment of noise-induced affection of the organ of
      hearing and hearing restoration in subjects occupationally exposed to noise.

PMID- 9163144
TI  - [The surgical treatment of obesity].

PMID- 9163145
TI  - [Surgery at a crossroads. 1926].

PMID- 9163146
TI  - [One-step transpleural or transmediastinal esophagogastroplasty in resection of
      the esophagus for cancer].
AB  - An experience with 139 radical one-step surgeries for esophagus cancer using
      transpleural or transmediastinal plasty with a gastric tube is presented. This
      type of surgery is a method of choice for malignant tumours of the esophagus
      since it provides the best radical operation and good functional results. The
      standardized approach to the anesthesiological maintenance of these surgeries and
      to postoperative intensive therapy is substantiated. The total postoperative
      mortality made up 26.2%; mortality from surgical complications-20.9%; 3-years
      survival was 24.5%; 102 patients (73.3%) were discharged from the clinic with
      good functional results.

PMID- 9163147
TI  - [Patient Helicobacter pylori infectivity after gastric resection].
AB  - The article is devoted to investigation of the Helicobacter pylori (HP) infection
      in 14 patients after resection of the stomach for ulcers of the gastroduodenal
      zone. Different methods were used for the assessment of the state of the gastric
      stump and gastroenteric anastomosis in the postoperative period. In most cases
      different degree of inflammatory alterations of the gastric mucosa were detected.
      In 2 cases (14.3%) peptic ulcers of the anastomosis developed. Changes to the
      gastric stump of 11 patients were associated with the HP infection which involved
      the mucosa of the anastomosed intestine in 8 patients. The data obtained point to
      possible participation of HP pathogenesis of the alterations detected after the
      stomach resection. The question of the expediency of a specific antibacterial
      therapy in the postoperative period and in treatment of certain kinds of
      postgastroresectional syndromes is raised.

PMID- 9163149
TI  - [The diagnosis and treatment of Dieulafoy's syndrome].
AB  - Dieulafoy's lesion is one of numerous causes of acute gastrointestinal bleedings.
      A prospective study of the Dieulafoy lesion were carried out from 1989 till 1995.
      Under study there were 8 patients. Acute Dieulafoy ulcers are most often localize
      in the upper third of the stomach and cause massive bleedings. The authors
      consider urgent laparotomy with gastrotomy, dissection of the ulcer and suturing
      the vessel to be the operation of choice.

PMID- 9163148
TI  - [An individual approach to the surgical treatment and medical rehabilitation of
      duodenal ulcer patients].
AB  - Since 1986 403 patients have been treated according to the following programme:
      successive preparation for surgery, the operative intervention chosen
      individually for each patient, the purposeful medical rehabilitation. Different
      types of vagotomy with draining operations were performed in 85.6% of the cases,
      stomach resection--in 14.4% of the patients. The mortality rate was 0%. The
      indications for various types of vagotomy, stomach resection and different types
      of draining operations were determined. Rehabilitation of 55% of the patients
      after the operative treatment took place at the gastroenterological department,
      the others--at an outpatient department. The indications for rehabilitation, its
      volume and time were established. The best remote results in the follow-up
      periods up to five years were obtained after truncal vagotomy and stomach
      resection. Ulcer recurrences were noted in 3.5% and 5.2% of the cases
      respectively. Recurrences of the disease were noted in 7.8% after combined
      vagotomy and in more than 20% after SPV. Nine patients out of 34 with recurrent
      ulcers were reoperated with good results, the others were successfully treated by
      conservative therapy.

PMID- 9163150
TI  - [The current problems of the surgical procedure in acute hemorrhages from
      gastroduodenal ulcers].
AB  - The article presents results of treatment of bleeding gastroduodenal ulcers in
      1010 patients for 23 years. The active temporizing policy during the first 8
      years resulted in 8.1% lethality while the active methods gave 8.24% lethality in
      six times greater number of patients. In the active policy urgent and emergency
      operations were performed on 43.6% of the patients with postoperative lethality
      12.9%. Lethality among non-operated patients was 4.6%. Using the active surgical
      methods allowed lethality to be substantially decreased in the group of non
      operated patients. The postoperative lethality was stabilized due to a less
      amount of recurrent bleedings and of "operations of despair". Recommendations are
      given to restrict the indications for Billroth-2 gastric resections because of a
      great risk of incompetent stump of the duodenum. Wider using the organ-saving
      operations is recommended, especially in elderly patients and against the
      background of haemorrhagic shock. The growing amount of patients with ulcerous
      gastroduodenal bleedings (which has become 2.4 times greater for the recent 15
      years) makes further investigations in this direction very actual.

PMID- 9163151
TI  - [The late results of the surgical treatment of perforated gastroduodenal ulcers
      in young people].
AB  - The article is devoted to surgical treatment of perforating gastroduodenal
      ulcers. An investigation of remote results of palliative and radical
      interventions for the perforation of the stomach and duodenum in patients of
      young age has shown that recurrent ulcers after suturing the perforation take
      place in 67.2% of the people operated upon against 21% of those subjected to
      bilateral truncal subdiaphragmatic vagotomy with pyloroplasty. A conclusion is
      made that for perforating ulcers it is expedient to perform radical operative
      interventions as a bilateral truncal subdiaphragmatic vagotomy with pyloroplasty.

PMID- 9163152
TI  - [Enzymatic pancreatogenic omental bursitis].
AB  - The most common causes of omental sac collections (OSC) are necrotic pancreatitis
      (90%) and pancreatic trauma (10%). Acute OSC is a form of local peritonitis in
      acute pancreatitis, subacute OSC are caused by internal pancreatic fistulas. The
      clinical and radiological signs, enzymatic activity of the exudate, morphological
      features of peritonitis were investigated. Treatment of acute OSC included
      conservative measures, of subacute OSC-surgical procedures.

PMID- 9163153
TI  - [The diagnosis and treatment of hormonally inactive adrenal formations].
AB  - Under analysis are results of an examination of 56 patients with hormonally non
      active tumors of the adrenals, 48 of them were operated upon. In 20 patients
      (35%) they had clinical manifestations, 16 patients (28%) had an elevated level
      of the 17-HCS and 17-CS excretion in the 24-hours urine. Morphological
      investigations of the tumors in 20 patients have revealed clear cell adenomas of
      the cortical layer of the adrenal, in 19 patients--tumoral cysts, in 3 patients-
      true cysts, in 1 case-myelolipoma, in 1 case--ganglioneuromyelolipoma, in 4 cases
      -hormonally non-active carcinomas of the adrenal cortex. The authors propose to
      designate the new formations described as hormonally non-active tumors of the
      adrenals. In view of the absence of absolute methods for the identification of
      malignancy of the tumors the operative treatment of them is proposed.

PMID- 9163154
TI  - [The surgical treatment of aneurysms of the abdominal aorta].
AB  - Based on an experience with treatment of 107 patients with aneurysms of the
      abdominal aorta subjected to planned or urgent operations the authors discuss the
      problems of the clinical course, diagnosis, indications for operative treatment,
      the technique of operative interventions and their results. In planned operations
      lethality was 4.1%, in ruptures of the aneurysm-64.2%. One year after the
      operations 90% of the patients were practically healthy, 5 years later they were
      70%.

PMID- 9163155
TI  - [Variants in the definitive organization of the lumbar lymph-conducting pathways
      in the applied aspect].
AB  - Topographic-anatomical investigations gave grounds for the description of 4
      stages of the development of the posterior parietal bed of the abdominal cavity.
      On the basis of the embryo-anatomical systematization three morpho-topographic
      types of the lumbo-lymphatic pathways were established: right-sided (20%), left
      sided (20%) and uniform (60%) types, each of them playing a certain part in
      metastasizing. Embryo-anatomical grounds are given for operative accesses to the
      superficial group of the right and left lumbar lymphatic pathways.

PMID- 9163156
TI  - [The connection between the duration of the course of postinjection abscesses and
      the biological characteristics of the causative microorganisms].
AB  - An analysis of results of treatment of 100 patients with postinjectional
      abscesses (PA) has shown their tendency to continuous inflammation in (23.9 +/-
      5.4)% of the cases. Under condition of long duration of PA microorganisms of
      Staphylococcus aureus species have been isolated which possess 2-6 times greater
      capacity for inactivating the natural antiinfectious resistance factors:
      lysozyme, complement, immunoglobulins, bacterial component of the interferon. The
      inclusion of oxytocin preparation into the scheme of treatment which inhibits
      manifestations of antilysozymal activity of staphylococci allowed the frequency
      of prolonged unfavourable periods of PA to be reduced to 10.9%.

PMID- 9163157
TI  - [The surgical treatment of gunshot wounds].
AB  - The authors have made an analysis of results of clinical observations of 953
      patients with gunshot wounds of soft tissues. It was found that primary surgical
      treatment (PST) of the gunshot wounds often proved to be not radical. Later it
      required reoperations in 30% of the wounded. To get more exact indications for a
      repeated surgical treatment it is necessary to make a careful revision of the
      gunshot wound within 3-5 days after getting the wound. The indications for
      reoperations are as follows: the development of secondary necrosis of the tissues
      necessary removal of the foreign body, opening of the pockets and leaks in order
      to provide valuable drainage as well as nonradical PST due to various causes.
      Reoperations performed according to the indications allowed to make the duration
      of treatment at an average 7 days shorter and the development of suppurations two
      times less frequent.

PMID- 9163158
TI  - [The diagnosis and treatment of injuries to the major vessels of the extremities
      and neck in wartime].
AB  - During the time of rendering special angiosurgical aid in the zone of military
      operations near the city of Gagra 28 wounded with gunshot injuries of major
      vessels of the neck and extremities were operated upon, which was 4.5% of all the
      wounded. Different procedures on the vessels were performed immediately after
      diagnosing the injuries within minimum terms after wounds in parallel with
      antishock measures. There was no intra- and postoperative lethality. Thrombosis
      of the restored arteries was noted in 4 out of all the patients operated upon.
      The extremity had to be amputated because of thrombosis of the operated artery in
      2 cases only which made up 7.2% of all the interventions performed.

PMID- 9163159
TI  - [The immediate results of treating gunshot injuries to the liver in penetrating
      abdominal wounds (based on data from a military garrison hospital)].

PMID- 9163160
TI  - [Problems of the surgical approach in splenic injury].
AB  - Under analysis is an experience with treatment of 187 patients with injuries to
      the spleen. Specific features of the clinical course, diagnostics and surgical
      methods are discussed. Splenectomy was necessary in 87% of the patients. Organ
      saving operations were possible in 13% of the patients. Postoperative lethality
      was 3.7%.

PMID- 9163162
TI  - [Complications after endoscopic interventions on the major duodenal papilla].
AB  - An analysis of 83 cases of complications following endoscopic procedures on the
      major duodenal papilla was made: 62 cases after 2110 retrograde
      cholangiopancreatographies (RChPG) and 21 after 620 endoscopic
      papillosphincterotomies (EPST). Among most frequent complications there were
      acute pancreatitis (49 cases), purulent cholangitis (11 cases), suppurations of
      the pancreatic cysts and purulent pancreatitis (8 cases). Bleedings took place
      after EPST in 11 patients. Risk factors of the development of acute pancreatitis
      were established: the presence of scarry stenosis of the papilla, chronic
      pancreatitis with the last exacerbation less than 1 month before the examination,
      more than 3 cannulations and contrasts of the pancreatic duct of the 2nd order or
      its acini, little (less than 10 mm) cuts of the papilla in EPST. Acute obturative
      pancreatitis is not a contraindication for EPST. On the opposite, after the
      procedure a rapid regression of the disease takes place. Asymptomatic
      hyperamylasuria observed in 329 patients (238 patients after RChPG and 91 after
      EPST) is considered to be a manifestation of flaccid pancreatitis, suggests a
      complication of the endoscopic procedure and is considered to be an indication
      for the corresponding treatment. Operations for the complications were performed
      on 21 patients. Four patients died because of complications of RChPG (0.2%) and
      two from complications of EPST (0.5%). Pancreonecrosis and purulent pancreatitis
      were causes of the deaths.

PMID- 9163161
TI  - [The humeral immunity indices of pleural exudate in the diagnosis and prognosis
      of the pleural complications after lung operations and chest trauma].
AB  - Examination of humoral immunity factors in the pleural exudate was carried out in
      49 patients: 15 patients had clotted postoperative hemothorax, 10 patients had
      bronchial fistulas after pulmonectomy, 24 patients were included in a control
      group. In patients with clotted postoperative hemothorax a decreased circulating
      immune complex (CIC) level in the pleural exudate was observed on the 10th-14th
      days followed by the elevation of the CIC level with a simultaneous increase in
      the IgA concentration and a decrease in the IgC and IgM concentration.
      Characteristic of the patients with bronchial fistulas and pleural empyemas was
      the two-fold increase of the IgA, IgM and IgG level in the pleural exudate as
      compared with the normal postoperative course.

PMID- 9163163
TI  - [Ultrasonic fistulography in surgery and urology].

PMID- 9163164
TI  - [The treatment of acute reflex urinary retention after operations in the area of
      the rectal sphincter].
AB  - The efficiency of a new peptide medicine-Prostatilen was studied when using it in
      acute postoperative retention of urine. Under observation there were 87 patients
      of 23-78 years of age after hemorrhoidectomy, plasty of the rectal sphincter or
      dissection of its fissure etc. The patients endured the treatment with
      Prostatilen well. Self-dependent urination was recovered during the nearest 40
      min after injection of 5 mg of the medicine. In the treatment of 23 patients it
      was used prophylactically before the appearance of a micturate urge. In 14 of
      them the postoperative period was smooth, in 9 patients the self-dependent
      urination was recovered following one additional injection. Clinical observations
      confirm that Proctatilen has a regulating effect upon the bladder tone which
      allows it to be recommended as a medicine for prevention of acute reflex
      retention of urine after operations in the area of the rectal sphincter.

PMID- 9163165
TI  - [A giant ulcer of the stomach with perforation into the liver simulating cancer].

PMID- 9163166
TI  - [A perforated stomach ulcer of 30 days' duration].

PMID- 9163167
TI  - [A gastro-omental-iliac venous shunt].

PMID- 9163168
TI  - [Superextensive resection of the intestines in acute intestinal obstruction].

PMID- 9163169
TI  - [Cardiomyoplasty--a surgical method of treatment in heart failure].
AB  - Until recently heart transplantation has been the only method of surgical
      treatment of severe myocardial heart failure. In the recent years operations of
      cardiomyoplasty have been performed more and more often for treatment of patients
      with this disease. The article presents the literature and personal data on the
      operation technique, indications and contraindications for it. First clinical
      results of the operative interventions fulfilled since 1994 are discussed.

PMID- 9163170
TI  - [The replacement of an infected branch of a vascular prosthesis with a portion of
      the superficial femoral artery].

PMID- 9163172
TI  - [The main trends in the hospitalization of patients with a diagnosis of "acute
      abdomen"].

PMID- 9163171
TI  - [Methods for estimating the severity of the status of resuscitated surgical
      patients].
AB  - The skin electric resistance in the representative points was measured by the
      Nakatani technique in 86 surgical patients during resuscitation. Two most
      informative indices were established: the average electric resistance of the skin
      and the renal index. A significant correlation (r = 0.78) was obtained between
      the average electric resistance of the skin and score sum SAPS. Changes of the
      renal index allow the dynamics of the patient's state to be estimated, and along
      with the electric resistance of the skin--the degree of traumatic consequences of
      the operative intervention. The method is simple and not dangerous for the
      patients.

PMID- 9163173
TI  - [Liver injuries].

PMID- 9163174
TI  - [Deep multilayer plastic repair in inguinal hernias].
AB  - The article presents the authors' variant of a surgical technique of
      hernioplasty, the so-called deep multi-layer hernioplasty. This type of
      hernioplasty is thought by the authors to give best results in patients with
      recurrent and so-called difficult inguinal hernias when there are true anatomic
      defects of the musculo-aponeurotic and fascial structures. Long-term results of
      35 operations were followed-up. Neither recurrences nor complications were noted.

PMID- 9163175
TI  - [The initial experience of using Vitaflon vascular prostheses in the sequelae of
      traumatic injuries to the major arteries].

PMID- 9163176
TI  - [Nonparasitic cysts of the spleen].

PMID- 9163177
TI  - [The efficacy of Mandel's jejunostomy in treating the dehiscence of esophago
      digestive anastomoses].

PMID- 9163178
TI  - [The laparoscopic removal of an adrenal tumor].

PMID- 9163179
TI  - [The use of a loop of small intestine for the formation of a bile duct in a 7
      month-old child in right-sided hemihepatectomy].

PMID- 9163180
TI  - [Duplication of the appendix in a child].

PMID- 9163181
TI  - [The scientific and practical medical journal Vestnik khirurgii im. I. I. Grekova
      in the past, present and future].

PMID- 9163182
TI  - [A retroperitoneal hematoma after appendectomy].

PMID- 9163183
TI  - [Hazards and complications in the diagnosis and treatment of acute appendicitis].

PMID- 9163184
TI  - [The prevention and treatment of postoperative thrombosis of the deep veins of
      the lower extremities (I. Prevention)].

PMID- 9163185
TI  - [In order to become a good surgery].

PMID- 9163186
TI  - [The pathophysiological basis of vagotomy in perforated duodenal ulcers].
AB  - Fractional intubation, intragastric pH-metry and other methods were used in
      complex examination of 107 patients who had perforated duodenal ulcers. The
      influence of surgical vagotomy upon the state of tissue blood flow was determined
      by means of polarography with a medicamentous vagotomy test. The medicamentous
      denervation was found to result in decreased blood supply of the acid-producing
      area and increased blood filling of the duodenum mucose. A conclusion is made
      that performing vagotomy is expedient after suturing the ulcer defect in patients
      having no diffuse purulent peritonitis.

PMID- 9163187
TI  - [The surgical treatment of gastroduodenal ulcers complicated by perforation and
      hemorrhage].
AB  - Medical histories of 67 patients with perforation of gastroduodenal ulcers
      combined with gastroduodenal hemorrhage were analyzed. The frequency of this
      complication makes 7.5% of all patients with perforated peptic ulcers. High
      mortality rate is thought to result from wrong diagnosis and inadequate
      operation. Best results were obtained when truncal bilateral subdiaphragmatic
      vagotomy was used in combination with some pyloroplasty techniques. Resection of
      the stomach is known to be dangerous because of frequent complications often
      leading to death. Operations aimed at the arrest of hemorrhage and liquidation of
      peritonitis are indicated to patients in critical state. X-ray examination of the
      abdomen and fibrogastroduodenoscopy allowed the combination of perforation and
      hemorrhage to be diagnosed in due time in all the patients.

PMID- 9163188
TI  - [The factors affecting patient survival after esophageal resection with single
      stage intrathoracic esophagogastroplasty].
AB  - Factors influencing the survival after resection of the esophagus with a one-step
      intrathoracic esophagogastroplasty were studied in 94 patients. In addition to
      the standard set of clinical data, under study were the parameters of central
      hemodynamics and external respiration functions. Risk factors of lethality were
      found. It was shown that the patient's age did not substantially influence the
      postoperative survival. Among the absolute contraindications to the one-step
      operation on the esophagus is the decompensation of cardiorespiratory functions
      and cachexia. The investigation of factors of risk of postoperative complications
      considered in groups allowed to pass to purposeful prophylactics of most probable
      of them.

PMID- 9163189
TI  - [The clinico-morphological characteristics, diagnosis and treatment of early
      stomach cancer].
AB  - Data on 90 patients with gastric carcinoma involving only the mucosa of the
      stomach wall are presented. All the patients were operated upon according to
      oncological principles. No regional metastasizing was observed at this level of
      invasion. Squamous-infiltrative tumors were found to be most typical (46.7%).
      Five-years survival after radical surgical treatment was 90.3%.

PMID- 9163190
TI  - [The choice of the treatment procedure in complicated forms of gallstones].
AB  - The article is devoted to an assessment of results of treatment of patients with
      complicated forms of cholelithiasis. Results of the treatment with active
      surgical measures and use of the endoscopic surgery methods are compared.
      Advantages of using endoscopy in algorithm of diagnostic and medical measures are
      shown. Recommendations are given concerning the terms and consequence of using
      the endoscopic methods of treatment.

PMID- 9163191
TI  - [Antioxidants in the treatment of cholelithiasis patients].
AB  - Results of examination and treatment of 157 patients with cholelithiasis against
      the background of a liver pathology were summed up. The antioxidant system in
      such patients was studied. The degree of a decrease of catalase activity in the
      liver and blood serum as well as the ascorbic acid content were found to depend
      on the liver state of patients with cholelithiasis. Greatest changes were found
      in patients with cirrhosis of the liver and chronic active hepatitis. The method
      of complex treatment of cholelithiasis patients with non-enzymatic antioxidants
      alpha-tocopherol and ascorbic acid is proposed. Activity of organ specific liver
      enzymes urokaninase and histidase was used for the estimation of treatment
      efficiency. Complex administration of ascorbic acid and alpha-tocopherol was
      shown to improve the liver function in patients operated upon for cholelithiasis.

PMID- 9163193
TI  - [The surgical procedure in tumor-induced colonic obstruction in patients at an
      elevated surgical risk].
AB  - A comparative assessment of results of palliative and radical operations in 250
      patients has proved efficiency of radical operations which were followed by less
      lethality rate in patients with high operative risk. A conclusion is made that
      wider indications to radical operations for patients of older age groups even
      those with different risk factors is one of perspective ways to improve results
      of surgical treatment of patients with obturative obstruction caused by colonic
      tumour of any localization.

PMID- 9163192
TI  - [Extracorporeal lithotripsy in combination with endoscopic papillotomy in
      choledocholithiasis].
AB  - Results of treatment of 30 patients of 50 to 90 years of age having
      choledocholithiasis by the method of extracorporeal lithotripsy (EL) combined
      with endoscopic operations on the major duodenal papilla are described. The first
      stage in the treatment was endoscopic papillosphincterotomy. There were 41
      sessions of EL (at an average 1,37 procedure for each patient). In 15 patients
      spontaneous excretion of the fragments from the common bile duct was noted. The
      endoscopic sanitation of the common bile duct with a removal of fragments with
      the Dormia basket was fulfilled in 13 patients after EL. The method of
      choledocholithotomy proved to be ineffective in 2 patients. Sanitation of the
      common bile duct was performed in all the patients before their discharge from
      the hospital. Thus the results obtained allow considering the extracorporeal
      biliary lithotripsy when combined with endoscopic papillosphincterotomy as an
      effective method for treatment of patients with choledocholithiasis which not
      only supplements traditional surgical procedures but also may be used as an
      alternative method of treatment especially for patients with high operative risk.

PMID- 9163194
TI  - [Combined operations in extreme forms of obesity].
AB  - The authors make an analysis of their experiences with combined operations for
      extreme forms of obesity in 93 patients. Indications to such operations were
      considered to be only the diseases which could cause complications of the early
      and late postoperative period. In spite of more pronounced signs of aggression
      the combined operations do not enhance frequency and severity of postoperative
      complications. Recommendations are given for the selection of anesthesia, the
      access and sequence of operation steps. Measures are proposed which allow the
      frequency of postoperative complications to be decreased from 59.8 to 29.8%.

PMID- 9163195
TI  - [Congenital unilateral pulmonary emphysema (Macleod's syndrome)].
AB  - The author analyzes the experience with diagnosis and surgical treatment of 5
      patients with one-side emphysema of the lung (McLeod syndrome). The leading
      symptoms of the disease were respiratory and cardiovascular disorders, their
      degree being dependent on the stage of compensation of the emphysema, the degree
      of displacement of the mediastinum organs, disturbance of bronchial passability,
      compression of the contralateral lung and concomitant diseases. The clinical
      picture and findings obtained by complex X-ray and angiocontrast methods of
      examination are considered to be the leading factors in diagnosing this
      developmental defect. Operations were made on 3 patients without lethal outcomes.

PMID- 9163196
TI  - [The low cardiac output syndrome after valve-conserving operations under
      hypothermia without perfusion].
AB  - Under study were the frequency of occurrence and causes of development of the
      syndrome of low cardiac output after the saving correction of mitral defects
      under conditions of cranio-cerebral (1st group-80 patients), general moderate
      (2nd group-130 patients) and deep hypothermia (open mitral commissurotomy-3rd
      group of 134 patients and reconstructive operations on the mitral valve-4th group
      of 104 patients). Frequency of development of the complication was reliably
      higher in groups with deep hypothermia (1.25% of patients in the 1st group, 9.2%
      in the 2nd group, 27.6% in the 3rd group, 25% in the 4th group). Factors
      influencing the development of the low cardiac output syndrome in patients of the
      2nd group was duration of the disease, in the 3rd group patients-the class
      according to the classification of the New York cardiological association and age
      of the patient, in operated patients of the 4th group it was the value of the
      cardio-pulmonary coefficient. Pharmaco-ice-chip cardioplegia used in patients of
      the 3rd and 4th groups failed to decrease frequency of the development of the low
      cardiac output syndrome in the postoperative period.

PMID- 9163197
TI  - [The efficacy of antithrombotic therapy after total obliteration-reversing
      therapy in atherosclerotic arterial occlusion of the lower extremities].
AB  - The operation of total desobliteration of the arteries (TDA) is a modification of
      semi-open eversive endarterectomy (EAE). Under study was frequency of thromboses
      of the desobliteration area, its correlation with postoperative changes of the
      state of hemorheology and hemocoagulation and the antithrombotic treatment of 150
      patients who were operated upon for total desobliteration of the iliofemoral
      popliteal segment. The patients were divided into 2 groups which had no
      substantial difference. At the postoperative period patients of the 1st group
      (79) were treated with Ticlid ("Sanofi" France) in dosage of 500 mg/day.
      Treatment of 71 patients of the second group included a combination of two
      medicines (A + D): aspirin--1000 mg/day and dipiridamol--150 mg/day. A
      comparative analysis of frequency of the development of cardio-vascular
      complications at the remote period has shown that in the first group of patients
      the frequency of development of acute myocardial infarction and acute disturbance
      of cerebral blood circulation was two times less than in the second group of
      patients. It is to be noted that in case of the developed in time occlusion in
      the operation area, the extremity was saved in the Ticlid group in 62% of cases
      (7 amputations per 18 cases of reocclusion) while in the (A + D) group the
      extremity was saved in 29% (17 amputations per 24 cases of thrombosis). Thus, the
      investigation of long-term results of TDA in combination with postoperative
      antithrombotic therapy of patients with atherosclerotic occlusions of the
      iliofemoral-popliteal segment arteries has shown high effectiveness of Ticlid. As
      compared with traditional methods of treatment with aspirin and dipiridamol
      treatment with Ticlid allowed the cases of restenosis and reocclusions to become
      more than two times less often.

PMID- 9163199
TI  - [The hemodynamic significance of normal vertical blood reflux based on
      dopplerographic data and in patients with primary varicose veins of the lower
      extremities].
AB  - Data of echophlebodopplerography on "ULTRA-PVD" (USA) were used for studying the
      frequency and hemodynamic significance of vertical reflux of blood in the deep
      veins of lower extremities in varicose patients. A group of 50 healthy men and
      women and 80 patients with different stage of varicose disease were studied. A
      comparison of the data obtained allowed determining a reliable static criterion
      of the retrograde wave duration when performing a test with proximal compression.
      It was shown that under normal conditions it should not exceed 1.5 sec. Three
      degrees of the retrograde blood flow were distinguished. Indications for surgical
      correction of the relative valve deficiency of the deep lower extremity veins
      must be established in each concrete case. Since 1993 200 patients with primary
      varicose veins have been examined and operated upon. Good and excellent results
      (96%) testify to the effectiveness of the correction of deep vein hemodynamics
      which can improve surgical treatment of this pathological condition.

PMID- 9163198
TI  - [Experimental and clinical research on the Russian Vitaflon blood vessel
      prosthesis].
AB  - The authors have performed an experimental and clinical assessment of a new
      graft. In 37 mongrel dogs 49 experiments were carried out with the implantation
      of grafts "Vitaflon" into different parts of the arterial and venous bed. It was
      shown that the domestic graft from modified polytetraftoroethylene had high
      biological inertia, good plastic properties, zero surgical porosity, strength and
      reliable "taking" by the recipient's organism. Following the experimental work
      the prosthesis "Vitaflon" (30-50 cm long and 8 mm diameter) was implanted in the
      femoro-popliteal-tibial position to 15 patients suffering from obliterating
      atherosclerosis of the lower extremity arteries. The period of follow-up
      observations was about 12 months. Thrombosis took place in two grafts in the
      early postoperative period. Other shunts were functioning well which was
      confirmed by the clinical picture and dopplerography.

PMID- 9163201
TI  - [The dynamic observation of patients with diffuse toxic goiter in the
      postoperative period by means of echography].
AB  - The authors used vernier calipers for measurement of the thyroid remnant during
      operation with special reference to data of an emergency histological analysis
      which determined the state of toxicosis, lymphoid infiltration, the presence of
      the extrafollicular epithelium. In addition, the patient's age, duration of the
      disease and taking thyreostatics was considered. It determined an individual
      approach to solution of the question of size of the gland to be left. The fate of
      the remnant thyroid was followed-up with the help of echography. In the majority
      of patients with diffuse toxic goiter a 90% increase of the remnant as compared
      with the initial data was noted in a month after operation, six months later it
      was 126%, a year later 186%. Close functional correlation was found between the
      data of histological investigations, age of the patients, duration of the disease
      and taking thyreostatics.

PMID- 9163200
TI  - [The dynamics of the enzyme system indices in the blood serum of patients with
      acute ischemia of the extremities].
AB  - The article presents an analysis of investigations performed for determining
      activity of certain enzymatic systems in the general and regional blood flow in
      55 patients with the syndrome of acute ischemia of the upper and lower
      extremities caused by embolism and arterial thrombosis. The dynamics of
      fermentemia depending on the degree of ischemia and adequacy of restoration of
      the blood circulation in the extremity involved was established. The levels of
      CK, LDH, AST and ALT in the blood serum of patients with regional ischemia was
      shown to be of great prognostic value.

PMID- 9163202
TI  - [Problems in the diagnosis and surgical care of thoracoabdominal wounds].
AB  - The article presents an 11 years experience in work of a specialized department
      of thoracoabdominal trauma with an analysis of treatment of 292 wounded. The main
      causes of the thoracoabdominal wounds (TAW) were knife stabs (96.2% of the
      patients). The diagnosis of injuries to vital organs of the chest and abdomen is
      known to be very difficult. The X-ray analysis is one of major diagnostic methods
      for TAW. Emergency thoracoscopy is of great significance in diagnosis of
      intrathoracic injuries and laparocentesis and laparoscopy are of great value for
      intraperitoneal wounds. The sequence of measures and surgery volume must be
      determined by the wound type and the severity of injuries of the internal organs
      which gives better results of treatment of such patients. Postoperative
      complications were noted in 9.1% of the wounded. Lethality was 5.1%.

PMID- 9163203
TI  - [The surgical procedure in left-sided thoracoabdominal knife wounds].
AB  - An experience with surgical treatment of 136 patients with left-side
      thoracoabdominal knife wounds has shown that all the patients can be divided into
      two groups: transpleural wounds (111 cases or 81.7%) and extrapleural wounds (25
      cases or 18.3%). Symptoms of extrapleural wounds (medial and lateral) are
      described. Injuries to organs of the abdominal cavity were shown to depend on the
      localization of the diaphragm wound. It was found that in patients with wounds to
      the posterior cupula there were only injuries of organs fixed in the
      subdiaphragmatic space.

PMID- 9163204
TI  - [Petr Aleksandrovich Dubovitskii (1815-1868)].

PMID- 9163205
TI  - [The treatment of appendicular peritonitis complicated by septic shock in
      childhood].
AB  - The article presents an analysis of results of treatment of 39 children from 1 to
      14 years of age with diagnosis of appendicular peritonitis complicated by septic
      shock. It was shown that complex pathogenetic treatment with controlled
      laparostomy, necessary compulsory or subsidiary artificial pulmonary ventilation
      before and after operative intervention, associated use of afferent methods
      allowed to decrease the number of lethal outcomes from 54.5 to 11.1%.

PMID- 9163206
TI  - [The advantages of laparoscopic inguinal herniorrhaphy in children].
AB  - An original method has been developed for laparoscopic suturing of the vaginal
      process of the peritoneum in inguinal hernia and Dupuytren's hydrocele in
      children which allows avoidance of surgical interventions on elements of the
      spermatic cord for saving full functions of the testicle. In 218 patients from
      1.5 to 15 years of age 230 laparoscopic operations were performed. No
      complications were noted. Control examinations within a week and one month after
      operation failed to reveal any anomaly on the part of the testicles and elements
      of the spermatic cord. The absence of the operation influence upon the blood
      supply of the testicle was confirmed by results of dopplerography of the
      spermatic cord vessels.

PMID- 9163207
TI  - [The correction of the disseminated intravascular coagulation syndrome in the
      emergency surgery of gastrointestinal tract cancer].
AB  - The authors estimate results of correction of the hemostasis system in surgical
      treatment of 63 patients with complicated carcinoma of the gastro-intestinal
      tract. It was found that purulent peritonitis, profuse hemorrhage and obturative
      obstruction facilitated the development of local and generalized DIC syndrome.
      Methods of correction of the hemostasis system, endogenous intoxication during
      preoperative preparing are described. Expedience of radical operations is
      stressed. Complex postoperative detoxication is recommended as well as measures
      for the restoration of activity of the vascular-thrombocytic hemostasis and
      prevention of thrombus formation.

PMID- 9163208
TI  - [The early diagnosis and treatment of influenza complications in servicemen].

PMID- 9163209
TI  - [The problem of suicides in society and the Armed Forces].

PMID- 9163210
TI  - [Lumbar sympathectomy in the combined treatment of obliterative vascular diseases
      of the lower extremities].

PMID- 9163211
TI  - [The intra-aortic antibacterial therapy of wounded patients with gunshot
      meningoencephalitis].
AB  - The original decision of permanent introduction of antibacterial means to tissues
      of brain at gunshot meningoencephalitis is offered. For antibacterial therapy the
      intra-aortal catheter with diameter of 2,5 mm (through a.femoralis) was
      introduced. After washing the catheter by solution of crystalloid with heparin
      the various combinations of preparations in 5% solution of glucose were
      introduced: cephalosporin--8 g/day; hentamicin and brumacilin--240 mg/day
      accordingly, amicacin--1500 mg/day. Speed of introduction--20-50 mg/h, total
      volume--500 ml. The catheter was in aorta not more than 10 days, maximum--14
      days. A described technique was applied in Burdenko Main Military Clinical
      Hospital on 34 wounded in head. At computer tomography of brain of all wounded
      intracranially the splinters and bullets were revealed, clinically-
      meningoencephalitis. Foreign bodies have been extracted after cupping of clinical
      and laboratory signs of meningoencephalitis. The authors consider, that the
      technique is effective not only at wounds of brain, but also at suppurative
      meningoencephalitis of other etiology.

PMID- 9163212
TI  - [The importance of clinical and instrumental indices in predicting cardiac rhythm
      disorders in hypertension].

PMID- 9163213
TI  - [The efficacy of using ozone preparations in the combined treatment of paranasal
      sinusitis].
AB  - In controllable study efficiency of application of ozone preparations in 39
      patients with acute and chronic purulent maxillary polysinusitis was studied.
      Purulent maxillary sinusitis, which in 44% was combined with frontitis and in 56%
      -with fronto-ethmoiditis was diagnosed in all patients. Besides traditional
      therapy all patients were washed out daily inflamed sinuses with 0.9% solution of
      sodium chloride, saturated of ozone. After washing out the sinuses were aerated
      during 15-20 minutes through paracentesis needles and catheters with ozone-oxygen
      mixture, containing 6 mg/l of ozone. Speed of mixture flow--1 1/min. To the half
      of patient with phenomena of intoxication were introduced I/V 400 ml of
      physiologic salt solution (ozone concentration--0.8 mg/l). Treatment rate is 3-6
      infusions. In patients pyorrhea and allocation of bacteria stopped 2-3 days
      earlier, than in control group, level of molecules of average weight was faster
      reduced to norm in the plasma of blood. Reduction of concentration of molecules
      of average weight corresponded to essential improvement of patient clinical
      condition (P < 0.01). Experience of ozone application testified about its high
      efficiency in paranasal sinusitis treatment.

PMID- 9163215
TI  - [The use of a low-intensity eddy-current magnetic field in treating patients with
      skin lymphomas].

PMID- 9163214
TI  - [A trial of using Geptral in patients with chronic liver diseases].

PMID- 9163216
TI  - [Current problems of military psychophysiology].

PMID- 9163217
TI  - [The outlook for the development of blood donation in the Armed Forces].

PMID- 9163218
TI  - [Mobile medical installations of the surgical type].

PMID- 9163219
TI  - [Zemstvo physicians, graduates of the Military Medical Academy who died
      fulfilling their service obligation].

PMID- 9163220
TI  - [A. L. Miasnikov and military naval medicine].

PMID- 9163221
TI  - [Aleksandr Nikolaevich Senenko (on the 75th anniversary of his birth)].

PMID- 9163222
TI  - [The legal bases for the hospitalization involuntarily of persons suffering from
      mental disorders].

PMID- 9163223
TI  - [The periods of actual bed occupancy per year and the length of stay of surgical
      patients in the hospital].
AB  - Taking into account the lack of science-reasonable data about average number of
      days of bed capacity in year and average number of days of various patient
      treatment in the hospital, the attempt is undertaken to substantiate these
      parameters in reference to DM of RF central military medicine institutions. In
      result of lead research it was established, that average terms of bed capacity in
      central military hospitals during the last 5 years were 310 days. Average patient
      terms of treatment differ essentially depending on age and contingent, that is
      necessary to take into account to define hospital bed requirement norms.

PMID- 9163224
TI  - [Report of the 51st Congress of the German Society of Digestive and Metabolic
      Diseases 18-21 September 1996 in Aachen].

PMID- 9163225
TI  - [Long-term results of endoscopic balloon dilatation of ulcer-induced pyloric
      stenoses--follow-up of 25 patients].
AB  - Long-term results of the "through the scope balloon dilatation" for treatment of
      benign pyloric stenosis are lacking. Therefore we retrospectively analyzed 25
      patients treated by balloon dilatation because of benign pyloric stenosis between
      1986 and 1995. The mean age was 63 years (18-88 years), there were twelve men and
      13 women. The mean follow-up period was 38 months (twelve to 120 months). 92% (23
      patients) underwent successful dilatation. 20% (five patients) presented with
      recurrent obstruction. They were treated again and none of them has had symptoms
      up to now. There were no complications due to dilatation. Through the scope
      balloon dilatation is a successful and cost effective therapy for benign gastric
      outlet obstruction also in long-term follow-up.

PMID- 9163226
TI  - [Primary amyloidosis of the gastrointestinal tract and liver--two case reports].
AB  - In primary amyloidosis the gastrointestinal tract and the liver are commonly
      involved, but clinical features and prognosis are mainly determined by the extent
      of cardiac and renal involvement. We review two cases with primary amyloidosis of
      the gastrointestinal tract and the liver. The predominant symptoms were
      malabsorption and hepatomegaly with cholestasis. The clinical aspects, diagnosis,
      treatment and prognosis of primary amyloidosis of the gastrointestinal tract and
      the liver are discussed in the context of the current literature.

PMID- 9163227
TI  - [Sequelae of cholecystectomy].
AB  - The removal of the gallbladder is followed by a number of compensatory changes,
      which in most cases do not result in clinical symptoms: the loss of the pressure
      reservoir for the bile, the duodenogastric reflux with a subsequent increase in
      gastric pH and helicobacter infections as well as alterations in bile metabolism.
      An increased incidence of colon carcinoma has been suggested to be caused by
      cholecystectomy. However, this might also be due to cholelithiasis. Abdominal
      symptoms widely regarded as postcholecystectomy syndrome are often due to
      functional disorders of the gastrointestinal tract and the unrelated to the loss
      of the gallbladder. Therefore, the expression postcholecystectomy syndrome is
      imprecise and should not be used in the future. Changes affecting the bile ducts
      such as sphincter Oddi dyskinesia, stones and stenoses are rare and treatment by
      endoscopic interventions is generally successful.

PMID- 9163228
TI  - [Endoscopy in patients at risk for bleeding].

PMID- 9163229
TI  - [Has the hemochromatosis gene been identified? A newly discovered MHC class I
      gene is mutated in patients with hereditary hemochromatosis].

PMID- 9163230
TI  - [Maintenance therapy in reflux esophagitis].

PMID- 9163231
TI  - [Endoscopic papillotomy with preservation of the gallbladder versus open surgery
      in risk patients with bile duct calculi].

PMID- 9163232
TI  - [Tissue oxygenation and microcirculation in dermatoliposclerosis with different
      degrees of erythema at the margins of venous ulcers. A contribution to
      hypodermitis symptoms].
AB  - BACKGROUND: In patients with chronic venous insufficiency erythematous areas in
      indurated skin (hypodermitis) and non erythematous areas of lipodermatosclerosis
      were examined. METHODS: In 13 patients with venous ulcers a total of 32
      localizations in more or less erythematous and indurated ulcer edges were
      measured. The amount of erythema was taken as an indicator for the extent of
      hypodermitis. The parameters examined were erythema (a-value), skin temperature
      (t), laser Doppler flow (LDF), transcutaneous (tcpO2) and intracutaneous oxygen
      tension (icpO2). According to the amount of erythema the different localizations
      were separated into two groups: areas with a-values lower than 14,2 were
      classified as lipodermatosclerosis without or with little erythema, are-as with a
      values higher than 14,2 were classified as areas of lipodermatosclerosis with
      extensive erythema. Identical measurements were also performed in healthy looking
      skin below the knee. RESULTS: Skin temperature and LDF were higher in areas with
      much erythema compared to those with little or no erythema. TcpO2, measured with
      an electrode temperature of 44 degrees C, was lower in areas with inflammation;
      tcpO2-values at 37 degrees C and icpO2-values showed no differences in ulcer
      edges with different amounts of inflammation. CONCLUSION: The results show
      differences of microcirculation between areas of lipodermatosclerosis with and
      without hypodermitis. These differences did not influence the actual tissue
      oxygenation in deeper parts in the dermis.

PMID- 9163233
TI  - [Scintigraphy studies of lymph flow in paralyzed upper extremities].
AB  - BACKGROUND: In paralysed limbs quite often edemas are seen, which might pose
      problems during rehabilitation. The origin of these edemas is not fully
      understood. METHODS: 48 patients with hemiplegia and edema of the paralysed arm
      were studied; in 40 patients lymphoscintigraphic studies (static and dynamic
      lymphography) were performed. RESULTS: In 80% of these cases lymphatic flow in
      the paralysed arm was increased compared to the healthy arm. If there was marked
      edema in the paralysed arm, the increase of lymph flow was considerable (p <
      0.01). CONCLUSIONS: Edemas in hemiplegic extremities are not due to lymphedema,
      as in lymphedema the lymph flow usually is very slow. They most likely are caused
      by disorders of filtration and reabsorption, due to a dysfunction of the
      autonomic nervous system.

PMID- 9163234
TI  - [Value of impedance rheography as a screening method in comparison with Doppler
      index in peripheral arterial occlusive disease].
AB  - BACKGROUND: Determination of the ankle-arm-index (AAI) by Doppler ultrasound is
      the method of choice as a screening test for peripheral arterial occlusive
      disease (PAOD). The easily performed Impedance Rheography (IR) may serve as an
      alternative screening method. This study investigates the correlations between
      parameters obtained by IR curve to the AAI. METHODS: 56 patients (62.8 +/- 13
      years, m = 37, f = 19) were included in the study. IR was performed on both
      shanks using ring electrodes below the knee and above the ankle (bipolar leads,
      frequency 90 kHz, test voltage 2.5 Vpp). The AAI was obtained by a 8 Mz
      ultrasound probe. RESULTS: AAI < or = 0.85 showed significant correlations (p <
      0.0001) to parameters of the IR curve: Crest Time (GZ, r = 0.67), Rise of the
      Pulse Wave (PA, r = 0.82), Relative Pulse Volume (RP, r = 0.82) and the
      Rheographic Quotient (RQ, r = 0.86). AAI > 0.85 showed no or only weak
      correlations to RI parameters. Underlying the following limits for rheographic
      parameters (GZ = 159 ms, PA = 3.3, RP = 0.43 vp/s and RQ = 0.4 vp), sensitivity
      and specify was determined: GZ: 68% and 100%, PA: 84% and 88%, RP: 68% and 92%,
      RQ: 77% and 88%. CONCLUSIONS: Impedance rheography correlates significantly with
      the AAI. Therefore this method seems to be well suited as a screening test for
      PAOD.

PMID- 9163235
TI  - [Reaction of the blood vessel wall to microporous endovascular prostheses].
AB  - BACKGROUND: Sealing endovascular prostheses enable transluminal exclusion of
      aneurysms, fistulas and arterial leakage. This study investigated the tissue
      response towards a newly developed microporous stent within the unaffected
      porcine aorta in respect to angiographic and histologic findings. METHODS: The
      device consisted of a self-expandable stent of wire filaments with integrated
      polyurethane. Under fluoroscopic guidance the stents (diameter 6 and 10 mm) were
      deployed into the infrarenal aorta of 3 animals. Follow-up was scheduled for 1
      month. Radiographs and angiographies were performed before, immediately after
      stent deployment and before the explantation procedure. The grafts were examined
      by light microscopy, immunocytochemistry and both scanning and transmission
      electron microscopy. Quantitative analysis was performed in respect to the tissue
      layers and the amount of polyurethane and elastin. RESULTS: Angiographic findings
      revealed stable stent position and patency without luminal narrowing. The trombus
      free luminal stent surface was 67%. The tissue response consisted in total tissue
      ingrowth through micropores forming an even neointimal lining (273 +/- 225
      microns). Restricted to the polyurethane a moderate foreign body reaction of
      giant cells was observed. The luminal surface showed focal endothelialization (19
      +/- 19%). The tunica media was diminished (from 767 +/- 146 microns to 312 +/-
      132 microns, p = 0.0001). The amount of elastin of the tunica media underlying
      the stent did not decrease essentially (from 3.63 +/- 1.25% in normal aorta to
      3.74 +/- 2.54%, p = 0.9221). The amount of polyurethane did not change in
      comparison to pre-implantation (19.4 +/- 0.9% and 18.3 +/- 3.2%, respectively, p
      = 0.6098). CONCLUSIONS: Reliable stent anchorage, incorporation of the stents in
      the underlying artery and a thin neointimal lining with focal endothelialization
      were obtained after the implantation of the covered microporous self-expandable
      stents in the porcine model.

PMID- 9163236
TI  - Diabetes mellitus is not a contra-indication for peripheral vascular intervention
      in patients with leg ischemia.
AB  - BACKGROUND: The effect of diabetes mellitus on the patency of peripheral vascular
      interventions was investigated in patients with arterial insufficiency of the leg
      in a retrospective follow-up study performed between 1993 and 1995. METHODS: In
      65 patients without and 36 with diabetes 124 vascular reconstructions were
      performed because of rest pain and/or ulceration. RESULTS: In diabetic patients
      ulcers were found more frequently and more distal bypasses were performed. No
      significant differences were observed between diabetics and non-diabetics as to
      bypass patency, number of re-interventions and amputations. Smoking and age were
      significant factors influencing bypass patency. CONCLUSION: Diabetes mellitus in
      patients with critical leg ischaemia appears to be no reason to refrain from
      vascular surgery.

PMID- 9163237
TI  - [Standardization of nailfold capillary microscopy in routine diagnosis].
AB  - BACKGROUND: Nailfold capillary microscopy is scientifically established and
      recognized as a diagnostic tool in clinical routine. It is, however, practiced in
      only a few centres. METHODS: But since a more widespread use of the method is to
      be expected for the near future, a consensus-meeting was held, where all German
      speaking clinicians and scientists, involved in capillary microscopy, were
      invited. Here, the technical procedure and the most important morphological
      parameters were evaluated and defined according to practical clinical aspects.
      RESULTS AND CONCLUSION: The main task of the consensus-meeting was to develop a
      standard evaluation sheet, accompanied by an explanation sheet. This standard
      evaluation sheet focuses on semiquantitative registration of morphological
      parameters like density, dilation, avascular fields, perivascular edema,
      microbleeding, torsion, atypical capillaries and giant capillaries. This standard
      evaluation sheet is to be validated by determining the inter-observer-variance.
      Later-on an illustrated practical guideline will be published.

PMID- 9163238
TI  - [Veno-lymphatic angiodysplasia as the cause of recurrent inguinal varicose
      veins].
AB  - Veno-lymphatic angiodysplasia may be the reason for the development of varicose
      leg veins. This form of angiodysplasia is illustrated by two case reports. Until
      now, angiodysplasia as possible cause of recurrent varicose veins after surgical
      treatment has not been included in the classification of the morphological types
      of recurrent varicose veins. The surgical approach exposing the common femoral
      vein in a first step and secondly performing a complete resection of the
      malformation with careful consideration of the adjacent femoral vessels is
      recommended as the treatment of choice.

PMID- 9163239
TI  - [Rectus sheath hematoma--detection of hemorrhage of ruptured aneurysm of the
      epigastric artery in CT].
AB  - A case of rectus sheath hematoma is described. Computed tomography demonstrated a
      still active bleeding from an aneurysm which was situated at the junction of the
      inferior and superior epigastric artery. The recognition of a continuous
      hemorrhage contributed to the decision of an immediate surgical intervention.

PMID- 9163240
TI  - [The spatial relationships and social structure of gerbils in the genus Meriones
      (Gerbillinae, Rodentia)].
AB  - Comparative analysis of spatial relations of 4 gerbil species (M. tamariscinus M.
      meridianus, M. libycus, M. unguiculatus) shows differences in the system of space
      use between species and within a species--between individuals of different sex.
      During reproduction period females are inclined to isolation, small overlap of
      home ranges and high degree of individualisation. Males occupy large home ranges
      overlapping with territories of several reproductive females. The territories
      occupied by the males of midday and tamarisk gerbils do not have clear boundaries
      and the level of their individualization is quite low. The males of Mongolian
      gerbil (M. unguiculatus) occupy well defined territories with high level of
      individualization. Spatial relations of M. libycus males are intermediate. The
      relationships of the males of three investigated species (M. meridianus, M.
      libycus, M. tamariscinus) being characterised by the high degree of asymmetry of
      pair connections, are organised according to the principle of agonistic
      dominance. Relationships between individuals of different family groups of
      Mongolian gerbils are based on the locus-dependent dominance, while within one
      family group-on principle of hierarchical subordination. The meaning of specific
      peculiarities in use of space and dominance relations are discussed in terms of
      reproductive strategies.

PMID- 9163241
TI  - [The clinical characteristics and diagnostic criteria of benign intracranial
      hypertension in children].
AB  - Combined investigation of syndrome of nonmalignant intracranial hypertension
      (NIH) was performed in 87 children at the age of 3-15 years. The following
      diagnostic criteria were determined: nonmalignancy of clinical course; residual,
      mainly nonprogredient character of cerebral pathology; subcompensated
      hydrocephalus or macrocephalus in more than 50% of patients with small
      enlargement of head circumference and of the size of cerebral ventricles
      (according to the data of computed tomography and echoventriculometry); triad of
      clinical manifestations in the form of headache, alterations of vision,
      oculomotor disorders; a positive effect of dehydrative therapy.

PMID- 9163242
TI  - [The formation of reactions of the cerebral cortical-brain stem structures to
      mild craniocerebral trauma in children].
AB  - 1,536 healthy children at the age from 20 days to 15 years were examined by means
      of EEG method after non-severe cerebrocranial trauma (CCT). Investigation of
      reactions of cortico-brain stem structures revealed some regularities in their
      development which depended on age: from visual absence of any EEG changes
      (because of immature cortico-brain stem and deficient links between them)--in
      babies, the signs of alterations of corticosubcortical relationships and
      irritation of mesencephalic-diencephalic structures (in children of the first
      years of life), to irritation of hypothalamic structures and increase of
      ascending activating influence of nonspecific media cerebral structures--in
      children after 7 years old. The above-mentioned alterations resembled quite well
      EEG changes of adult patients' brains in process of decreasing of CCT severity
      and correlated also with dynamics of reverse development of pathological process
      after severe CCT.

PMID- 9163243
TI  - [Psychosomatic motor disorders in the structure of depression in children and
      adolescents].
AB  - 106 patients (40 boys and 66 girls) at the age from 3 to 15 years with depression
      of neurotic level with motor disorders (hyperkinetic, hypokinetic,
      pseudoepileptic) were examined. The motor disorders were estimated as
      pseudoneurological ones. The treatment of such patients must be performed with
      estimation of the typological variations of depression (asthenic type was
      observed in 31 cases, anxious type--in 37, melancholic type--in 6, combined type-
      in 32), of the degree of depressions manifestation, of their etiology as well as
      the pathological "basis" and personal peculiarities of the patients. 81 patients
      were treated by antidepressants (AD) in combination with tranquilizers and
      nootropes. AD weren't applied in 25 cases. Of all the patients in which AD were
      used complete correction of pseudoneurological and depressive disorders was
      observed in 46 cases (56.8%), considerable improvement--in 26 patients, the
      improvement--in 9 cases. Meanwhile improvement was observed only in 15 cases and
      slight improvement in 10 persons in patients who had not received any AD (group
      differences were significant).

PMID- 9163244
TI  - [The color preferences of adolescents with character traits].
AB  - An experimental study has been conducted of validity of Lusher's "Clinical Colour
      Test" concerning the types of accentuations of characters according to
      classification of A. E. Lichko. The new informational indices were suggested,
      namely: "the sum of the main colours" (sigma n) and "the coefficient of the
      correlation of the sums of the main colours" (K(m)). These indices were absent in
      a classical variation of the test. The results of investigation showed the
      validity of Lusher's test for evaluation of the majority of accentuations types
      as well as of deliquency and organic basis of pathocharacterological deviations.
      It was also emphasized that the diagnosis of accentuations types by means of
      Lucher's test was possible only with consideration of correlation of preferences
      of "main colours". The conclusion was made about perspectivity of application of
      Lusher's test for both group and individual diagnosis.

PMID- 9163245
TI  - [The laser therapy of children with Tourette's syndrome].
AB  - The method of pathogenetic treatment of patients with Tourette's syndrome (TS) by
      means of low-intensity infrared laser irradiation was elaborated. Both elevation
      of the level of xantine oxidase, the inducer of lipid peroxidation, and the
      decrease of activity of superoxide dismutase, enzyme of the antioxidative
      defence, were revealed. The correction of antioxidative system was carried out by
      means of method of over venous laser irradiation of blood together with
      administration of decreased doses of neuroleptics (orap and haloperidol). Thus,
      the compensation of patients' clinical state was achieved. The elevated doses of
      neuroleptics were necessary in control group (without laser therapy application).
      The stability of the effect was observed in a year according to clinical and
      biochemical findings.

PMID- 9163246
TI  - [The clinico-electroneuromyographic characteristics of acute inflammatory
      polyneuropathies in children].
AB  - Clinical electroneuromyographic examination (ENME) was carried out in 59 children
      at the age of 1-12 years with acute demyelinating polyneuropathies (PNP). The
      patients were divided into two groups, namely: 24 children with Guillain-Barre
      [correction of Giyenne-Barret] syndrome (the first) and 35 ones with diphtheritic
      PNP (the second group). The main clinical symptoms were investigated in each
      group. As a result of ENME investigation the axonal and demyelinating types of
      PNP's beginning were identified. They were distinguished both by severity of
      course and by rate of restoration. Diphtheritic PNP was characterized by
      demyelinating type of pathology rise with addition of axonal component in severe
      cases. The conduction through the additional nerves was investigated to prognose
      the development of bulbar disorders in PNP.

PMID- 9163247
TI  - [The neuroradiological aspects of infantile spasms].
AB  - The observation of 38 children with early form of children epilepsy that is with
      syndrome of infantile spasms (IS) was performed by means of computed tomography
      of the brain. The structural alterations of the brain were revealed in 89.5% of
      cases. They varied from rough developmental anomalies and pronounced destructive
      phenomena to microdysgenesias and moderate cortical atrophies. These changes were
      systematized according to the time of the beginning of some alteration on the
      definite stage of neuro-ontogenesis. There were embryofetal disturbances (23.6%),
      peri- and postnatal alterations (50%) and combined ones (15.7%). The definite
      correlation was established between neuroradiological damages, clinical pattern
      of IS, differentiated policy of the treatment and the prognosis of neuropsychic
      development of a child.

PMID- 9163248
TI  - [Nerve tissue-specific proteins in the assessment of the permeability of the
      hemato-encephalic barrier in comatose states in children].
AB  - The role of functional state of hematoencephalic barrier (HEB) was estimated in
      terms of development of pathological process in coma. The quantitative
      determination of neurospecific protein (NSP), exactly of alpha 1 and of alpha 2
      cerebral globulins (produced by astrocytes and oligodendroglial cells) was used
      for estimation of HEB state. The clinical examination of 138 children in comatose
      state caused by different factor (meningitis, encephalitis, cerebrocranial
      trauma, infectious toxicosis) was performed. Enzyme immuno-assay of alpha 1 and
      of alpha 2 cerebral globulins allowed to control HEB's functional state
      objectively in "brain-blood" direction: in cases of alteration of HEB's function
      the autoantibodies to NSP may penetrate into cerebral tissue and cause
      nonspecific reaction in form of edema or inflammation. The membrane stabilizing
      effect of Dexamethazone was established.

PMID- 9163249
TI  - [An elevation in the level of autoantibodies to nerve-growth factor in the blood
      serum of schizophrenic children].
AB  - The level of autoantibodies (AAB) to nerve growth factor (NGF) was examined in
      blood of mentally healthy children, children with early children schizophrenia as
      well as with Kanner's and Asperger's syndromes too. The elevated titer of AAB to
      NGF was determined in blood of children with acute, active state of disease;
      meanwhile the same titer wasn't changed in the state of stable remission or
      steady defective state as compared with control group. The correlation was found
      between the level of AAB to NGF and the degree of disease progression. The
      correlations which were revealed between AAB to NGF level and peculiarities of
      the clinical state of patients permitted to use this index as the objective
      marker of both the acuteness and the severity of the patient's state.

PMID- 9163250
TI  - [Epilepsy and dreams in children].
AB  - 24 patients at the age of 10-18 years with different forms of epilepsy and 10
      healthy children and juveniles were examined. The analysis of dreams testified
      both intensification and quantitative peculiarities of dreams in epileptic
      patients. Their specific features were: frightening character, stereotypy,
      brightness and contrastness of colour images as well as psychosensory disorders
      and sensations of different modalities, peculiar and original topic. The dreams
      characteristic for epilepsy arise frequently long before the objective clinical
      manifestation and might serve as one of the important markers of cerebral
      epileptisation.

PMID- 9163251
TI  - [Benign intracranial hypertension in children].

PMID- 9163252
TI  - [The diagnosis and treatment of the attention deficit syndrome in children].

PMID- 9163253
TI  - [Central core disease (its clinical and laboratory diagnosis)].

PMID- 9163254
TI  - [An epileptic syndrome in infantile cerebral palsy].
AB  - The results of examination of 102 patients with infantile cerebral paralysis
      (ICP) with epileptic syndrome (ES) at the age from 3 months to 14 years are
      presented. Epileptic fits predominated in patients with hemiparetic form of ICP
      (40.8%) and spastic diplegia (32.4%). ES manifestations were observed in ICP
      during the first 3 years of life (more than 80% of cases). The peculiarities of
      ES clinical course were revealed. There were determined the main types of
      seizures in patients with ICP which depended on age of their manifestation, as
      well as their further transformation and prognosis. Computer tomographic and EEG
      correlations were established in different forms of ICP. They permitted to
      revealed pathogenetic mechanisms of ES development in patients with ICP and to
      determine therapeutic policy and prognosis of the disease.

PMID- 9163256
TI  - [Validity of a liquid chromatographic (HPLC) method for the determination of
      ticlopidine in human plasma].
AB  - A simple high-performance liquid chromatographic method for determination of
      ticlopidine in human plasma using UV detection was developed. The separation of
      the investigated compound and internal standard was achieved on "BST Rutin" 10,
      C18 BD column with a 0.01 M, (pH 4) potassium dihydrogen phosphate
      bufferacetonitrile-methanol (20:40:40 v/v) mobile phase. The detection was
      performed at 215 nm. The compounds were isolated from plasma by Bond Elut C18
      solid-phase extraction, the mean absolute recovery was 84.9%. The limit of
      quantitation was 10 ng/ml, the limit of detection was 5 ng/ml. The assay has been
      validated with respect to accuracy, precision and system suitability. All
      validated parameters were found to be within the necessary limits. The developed
      analytical method for ticlopidine was found to be suitable for application in
      pharmacokinetic studies and human drug monitoring.

PMID- 9163255
TI  - [Formulation and in vitro examination of furosemide-containing suppositories and
      preliminary experiences of their clinical use].
AB  - Rectal suppositories containing Furosemide (4-Chloro-N-furfuryl-5
      sulfamoylanthranilic acid) and Furosemide Sodium were formulated with various
      suppository bases. The in vitro drug release of Massa Estarinum 299 proved to be
      the best from among the vehicles having various physical-chemical properties. The
      diuretic effect of the two suppositories was compared in a prospective, cross
      over clinical trial including 8 patients. Both preparations have induced and
      increase of urine flow, which was comparable to the diuretic effect of the
      tablet. Thus the possibility of rectal use has been added to the modalities of
      therapeutic Furosemide administration.

PMID- 9163257
TI  - [Pharmacokinetics of rectal absorption of amodiaquine in rabbits].
AB  - Experimental investigations were made in rabbits to examine the rectal absorption
      of antimalarial amodiaquine [AQ]. To calculate the pharmacokinetic parameters AQ
      was administered orally (20 mg/kg) and rectally (20 mg/kg) to the animals and the
      blood concentrations of the drug were controlled during a time interval of 120
      hours with help of spectrofluorometric method. The pharmacokinetic analysis was
      performed by use of two-compartment open model system. Time-concentration curves
      were fitted to the data in experiments by computer program (MEDUSA) and the
      kinetic parameters were given in the Tables 1. and 2. It was established that
      rectally administered AQ resorbed not only from solution but from suppository,
      too. The bioavailability of the rectal preparations relating to the oral dosage
      form was 63.35% and 68.70%, respectively. The most appropriate drug delivery
      system for rectal application had been selected previously.

PMID- 9163259
TI  - [Palliative treatment. A medically and ethically relevant field of activity for
      the anesthetist].

PMID- 9163258
TI  - [Chemical tests with Marrubium species. Official data on Marubii herba in
      Pharmacopoeia Hungarica VII].
AB  - About 40 species of the Marrubium genus (Lamiaceae) are known of which 2 species
      (M. vulgare L. and M. peregrinum L.) and one hybrid (M. x paniculatum Desr.) can
      be found as native plants in Hungary. The above-ground parts of M. vulgare L. are
      official in Hungarian Pharmacopoeia VII. Active substances in Marrubii herba are
      labdane-structured bitter materials. Although the presence of furanic labdane
      diterpenes in the plant is known, the pharmacopoeia gives only microscopic tests,
      qualitative tests (for other parts of the plant and foreign organic matter) for
      the bitter value of Marrubii herba. We have examined the main terpenoid
      substances isolated with column, gel and preparative layer chromatography.
      Structure elucidations were performed by means of UV, mass and NMR spectroscopy.
      We have compared the changes in terpenoid-type compounds (premarrubiin and
      marrubiin) in plants during the vegetation period; in different Marrubium species
      and in the different extractions of horehound by means of thin layer
      chromatography and densitometry. By reason of our results we propose qualitative
      and quantitative chemical tests for the paragraph of Marrubii herba in
      Pharmacopoeia Hungarica VII.

PMID- 9163260
TI  - [Palliative medicine].
AB  - Palliative medicine has its origin in the modern hospice movement. It is based
      upon an integrated-care concept for seriously ill and dying patients. The first
      consideration of this particular form of treatment is not to prolong life, but to
      reach the best possible quality of a patient's remaining lifetime. Therefore,
      palliative medicine consists of: (1) excellent pain treatment and symptom
      control; (2) an integrated approach towards the psychic, social, and spiritual
      needs of the patient, relatives, and attending staff during the periods of
      illness, dying, and, after the patient's death; (3) competence in dealing with
      vital matters of communication and ethics; and (4) acceptance of death as a
      normal process. Palliative medicine clearly rejects euthanasia. Practical
      implementation of the idea of hospice services can be realised anywhere when
      taking care of seriously ill and dying patients, whether at home, in a nursing
      home, or in hospital. Experience shows that quite a few patients cannot be
      treated successfully without additional services, such as home-care services, day
      care centres, in patient hospices, and palliative-care units. Up to now, severely
      ill tumour patients have benefited most from these services. In palliative care
      units an interdisciplinary team of doctors and nursing staff assisted by
      physiotherapists and members of psycho-social professions is taking care of and
      treating patients. Additional support is given by voluntary services and the
      integration of the patient's relatives in the caring process. Palliative medicine
      is the overall term for this special kind of treatment and care. In Great
      Britain, Canada, and Scandinavia considerable progress has been achieved in this
      field, including recognition as an independent clinical discipline and the
      establishment of lectureships in palliative medicine.

PMID- 9163261
TI  - [The preemptive action of ketoprofen. Randomized, double-blind study with
      gynecologic operations].
AB  - STUDY OBJECTIVE: Ketoprofen exerts its clinical effect by inhibition of
      prostaglandin synthesis, but also acts as an NMDA-receptor antagonist by means of
      the kynurenic acid. Based on ketoprofen's supposed central mechanism of
      analgesia, we expected a preemptive effect, which was assessed by the present
      study. METHODS: In a prospective, randomised, double-blind investigation of 48
      patients undergoing gynaecological procedures (laparotomy, pelvioscopy), the
      first group received ketoprofen 2 mg/kg body weight i.v. 20 min before the
      beginning of surgery and placebo i.v. at the end of surgery. In the second group,
      placebo was administered first and ketoprofen at the end of surgery.
      Premedication and anaesthesia were standardised by protocol. The postoperative
      analgesic patient-controlled analgesia consumption by was also standardised
      (piritramide). Efficacy was assessed by visual analogue scale (VAS) and total
      requirement of analgesics within the first 24 postoperative hours. The time to
      the first request for postoperative analgesics was also recorded. Safety was
      assessed by continuous monitoring of vital parameters such as respiratory rate,
      heart rate, blood pressure, and oxygen saturation. The incidence and severity of
      adverse events was documented. RESULTS: There were no significant differences
      between the groups in demographic data or type or duration of surgery. The time
      to the first request for analgesic, VAS pain intensity, and analgesic consumption
      in the first 24 h post-surgery were not significantly different between the
      groups (t-test). CONCLUSION: Ketoprofen is an effective post-operative analgesic
      in combination with an opioid, but has no preemptive effect according to the
      results of this study.

PMID- 9163262
TI  - [Treament of morphine-induced constipation with oral naloxone].
AB  - INTRODUCTION: Almost all patients treated with opioids suffer from constipation.
      Numerous laxatives are used to overcome the problem, but none has yet been found
      to yield favourable results in all patients. Several studies have attempted to
      reverse opioid-induced constipation by the use of oral naloxone. Experiments
      carried out in rats showed that morphine-induced constipation is reduced by oral
      naloxone without impairment of antinociception [4]. However, evaluation of
      clinical studies reveals that there is uncertainty about the dosage regimen (the
      daily dose of naloxone ranged from 0.5% to about 60% that of morphine) and a lack
      of larger numbers of patients studied. METHODS: Fifteen patients suffering from
      opioid-induced constipation participated in the present study. Constipation had
      been present for 5 to 14 days despite the use of laxatives. According to the
      results obtained in the animal experiments [4], it was originally planned to
      administer oral naloxone at a dose ratio of 1:1 with respect to morphine on day 1
      and 2; reducing it on day 3 and 4 to one-half and then to one-fourth of the
      initial dose on day 5 and 6. RESULTS: Twelve patients experienced a strong
      laxative effect with spontaneous bowel evacuation 1 to 4 h after the first intake
      of oral naloxone. Three patients had no laxative effects even after repeated
      doses. Eleven of the 15 patients reported an average loss of 10%-15% of analgesia
      after oral naloxone as measured by visual analogue scales. Increasing the
      morphine dose by about 15% restored the previous level of analgesia without
      reappearance of constipation. Eight of the 12 patients having a laxative effect
      experienced abdominal cramps, and therefore, the total dose of naloxone was
      reduced on day 2 to 2%-15% of that originally planned; this dose still produced a
      laxative effect. Four of the 15 patients had a withdrawal syndrome. A single dose
      of morphine equivalent to their daily morphine intake abolished the symptoms.
      DISCUSSION: The medical history of the 3 patients in whom naloxone failed to
      abolish constipation revealed neurological disturbances. Treatment of these
      patients included the use of neuroleptics, antiemetics, and other drugs. In this
      context, it should be noted that oral naloxone can be expected to abolish only
      opioid-induced constipation. In conclusion, it was found that the treatment of
      opioid-induced constipation by administration of oral naloxone produced positive
      results. A controlled study will show, whether the side effects can be minimized
      by reducing the naloxone dose.

PMID- 9163263
TI  - [Combined 3-in-1 sciatic block. Prilocaine 500 mg vs. 650 mg].
AB  - The objective of the study was to investigate the clinical effectiveness of
      increasing the dosage of prilocaine for a combined 3-in-1/sciatic nerve block
      from 500 to 650 mg (open study with 29 patients compared with 30 patients from a
      former study) and to validate these findings in a second stage (randomised study
      comparing two groups of 30 patients each). Not only was clinical effectiveness
      improved by increasing the dose to 650 mg, but methaemoglobinaemia and toxicity
      were not relevant problems. With the higher dosage, development of the block was
      slightly faster (onset and completion); there were fewer unsatisfactory blocks;
      and clinically relevant plasma levels of methaemoglobin did not occur.

PMID- 9163264
TI  - [The temperature-humidity profile of the PhysioFlex. Studies on a model].
AB  - Closed-system anaesthesia provides the best prerequisites for optimal warming and
      humidification of anaesthetic gases. The PhysioFlex anaesthesia machine
      fascilitates quantitative closed-system anaesthesia. Furthermore, its design may
      improve the climatization of the anaesthetic gases by revolving the system volume
      at 70 l/min, using a small soda-lime canister to allow optimal usage of the heat
      and moisture generated by CO2 absorption and by integrating all system components
      in thermally isolating housing. To determine the capacity of the PhysioFlex to
      climatize anaesthetic gases, we evaluated the heat and humidity profile at four
      characteristic places in the anaesthetic circuit under standardised conditions in
      a model. MATERIALS AND METHODS: In an air-conditioned room at 19-20 degrees C
      ambient temperature, the PhysioFlex was operated with a fresh gas flow of less
      than 500 ml/min, similar to quantitative closed-system anaesthesia in adults.
      With a respiratory rate of 10/min and a tidal volume of 600 ml, a humidifier was
      ventilated, that delivered humidity-saturated gas at 33-34 degrees C; 200 ml/min
      CO2 were added to the system at the humidifier to mimic the heat, moisture, and
      CO2 input of a patient into the anaesthetic circuit. A total of six series were
      performed, each starting with a cold and dry anaesthetic circuit. For 2 h the
      time-courses of temperature and humidity of the anaesthetic gases were measured
      at four distinct places: (1) in the soda-lime canister (M1); (2) at the outlet of
      the anaesthesia machine (M2); (3) at the inlet of the anaesthesia machine (M3);
      and (4) in the inspiratory limb close to the Y-piece (M4). Capacitive humidity
      sensors (VAISALA Type HMM 30 D without a protective cap) and very small
      thermocouples were used to measure relative humidity (rH) and temperature. The
      data were recorded at 5 min intervals. Due to the continuous gas stream in the
      system, the response time of the sensors, which is in the range of a few seconds,
      did not affect the accuracy of the measurement. With the temperature-dependent
      humidity content of 100% rH obtained from equation 1, absolute humidity was
      calculated. RESULTS: The time courses of temperature and humidity at the
      different measuring points are depicted in Figs. 2 and 3, respectively. The
      steepest increase in temperature and humidity was observed at M1. Within 10 min
      100% rH was achieved at all measuring points. Initially, there was a considerable
      temperature gradient between M1 and M2; this became gradually smaller, indicating
      system components with high heat capacities. There was only a small gradient
      between M2 and M4, indicating that there was only a small heat loss compared to
      the heat input. The recommended minimal climatization of the anaesthetic gases of
      20 mg H2O/l [20] was obtained within 10 min at M4. During the whole measuring
      period heat and humidity increased in the system, reaching a maximum at M4 after
      120 min with average values of more than 28 degrees C and 27 mg H2O/l,
      respectively. CONCLUSION: With the PhysioFlex anaesthesia machine employing
      closed-system conditions, minimal climatization of anaesthetic gases was reached
      within 10 min. After a period of 120 min, the anaesthetic gases were nearly
      climatized to the extent recommended for long-term respiratory therapy. To date,
      no comparable temperature and humidity level has been reported with conventional
      anaesthesia machines. The time course of the gradient between M1 and M2 may give
      an opportunity for further optimising the system in reducing heat loss after the
      soda-lime canister, the active heat and moisture source in the circuit. At about
      32 degrees C, the temperature in the soda-lime canister is 10-15 degrees C less
      than in conventional anaesthesia machines. Thus, the use of thermally instable
      volatile anaesthetics in the PhysioFlex under closed-system conditions may be
      less critical than in conventional anaesthesia machines under minimal-flow
      conditions.

PMID- 9163265
TI  - [Generalized gas gangrene infection with rhabdomyloysis following
      cholecystectomy].
AB  - We report a rare case of spontaneously developing generalised gas gangrene with
      massive rhabdomyolysis after a cholecystectomy and drainage of a hepatic abscess.
      On preoperative physical examination the patient appeared severely ill and was
      icteric and oliguric. Laboratory evaluation showed signs of systemic
      inflammation, elevated lactate levels, evidence of disseminated intravascular
      coagulation (DIC), and increased levels of serum creatine kinase (CK) activity.
      Abdominal ultrasound and endoscopic retrograde cholangiography showed a
      gallbladder perforation and a hepatic abscess. Cholecystectomy and drainage of
      the abscess was performed immediately and without technical problems. After
      postoperative admission to the intensive care unit, the patient showed evidence
      of generalised myonecrosis with subcutaneous gas formation and acute renal
      failure. Initially, there were few other signs of systemic toxicity; the patient
      was not hypotensive and the pulmonary gas exchange was normal. Within hours
      diffuse swelling of his right leg developed with cutaneous gangrene and a
      compartment syndrome. After fasciectomy and extensive surgical debridement,
      uncontrollable bleeding due to DIC developed from the fasciectomy site, which
      finally required exarticulation of the leg at the hip joint. At this point,
      multiple organ failure including severe adult respiratory distress syndrome was
      present. Two days after cholecystectomy, the patient died from hypoxic
      cardiocirculatory failure. Clostridium perfringens was repeatedly isolated from
      the wounds. Besides gas gangrene, the differential diagnosis of such infections
      includes localised clostridial cellulitis, nonclostridial anaerobic cellulitis
      caused by mixed aerobes and anaerobes, and type I or type II necrotising
      fasciitis. Patients with systemic necrotising infections should be treated with
      broad-spectrum antimicrobial regimens (penicillin G, 3rd generation
      cephalosporins, clindamycin, and aminoglycosides). An otherwise unexplained
      elevation of serum CK activity in the presence of acute cholecystitis may suggest
      haematologic spread of an aggressive myolytic agent and the beginning of
      myonecrosis. This should prompt immediate surgical exploration after establishing
      broad-spectrum antibiotic coverage. The role of hyperbaric oxygen treatment in
      this situation remains to be established. If hyperbaric oxygen is to be employed,
      it should neither delay surgical exploration nor jeopardize the patient with the
      hazards of an interhospital transport.

PMID- 9163266
TI  - [Prolonged muscle weakness in intensive care patients with special attention to
      the so-called intensive care polyneuromyopathy].
AB  - Generalized muscle weakness in critically ill patients can result in prolonged
      periods of artificial ventilation and longer stays in the intensive care unit.
      Both neuropathic (critical illness polyneuropathy) and myopathic (critical
      illness myopathy) abnormalities seem to play an important role for this prolonged
      weakness. This article reviews its complex differential diagnosis with special
      emphasis on the current understanding of the neuromuscular syndromes. An
      efficient diagnostic plan is necessary for the exclusion of other curable causes
      of prolonged muscle weakness even in the presence of polyneuromyopathic changes.
      Psychological support of the patient and prophylaxis of secondary complications
      of prolonged immobilization are crucial when specific therapy is not possible.

PMID- 9163267
TI  - [New mechanical methods for cardiopulmonary resuscitation (CPR). Literature study
      and analysis of effectiveness].
AB  - In a recent German multicenter study, 25% of the patients who suffered a
      witnessed cardiac arrest outside the hospital were resuscitated successfully and
      were discharged from the hospital. Approximately 100,000 people suffer a fatal
      cardiac arrest in Germany annually, which is about ten times more than deaths
      resulting from motor vehicle accidents. New devices and techniques for
      cardiopulmonary resuscitation (CPR) have been developed in order to enhance the
      efficacy of chest compressions during CPR. The purpose of the present article is
      to review mechanisms of blood flow during CPR, to discuss CPR devices and
      techniques (vest CPR, CPR with interposed abdominal compressions, active
      compression-decompression (ACD) CPR, phased chest and abdominal compression
      decompression CPR, and to further evaluate results from subsequently published
      laboratory and clinical studies. Vest CPR performs chest compressions with a
      pneumatic pump, which is able to compress the entire thorax with great force
      while minimizing injury. This device was developed to achieve an optimal driving
      force of the thoracic-pump mechanism during CPR. After promising results in
      laboratory studies and further technical development, vest CPR increased coronary
      perfusion pressure (CPP) in a clinical study even after 45 min of unsuccessful
      advanced cardiac life support. Currently, this device is being evaluated in an
      international multicenter study in Europe and the United States. A vest for
      employment by the emergency medical service (EMS) is in preparation. Interposed
      abdominal compressions during relaxation of the chest may augment artificial
      blood flow. In some laboratory studies, this mechanism resulted, in part, in
      promising data, and in another did not achieve better survival rates in
      comparison with standard CPR. No benefit of abdominal compressions was shown in
      an investigation in an EMS, whereas in a clinical study patients who were treated
      with interposed abdominal compressions were more likely to survive and be
      discharged from the hospital. However, in a follow-up study of in-hospital
      patients with asystole or pulseless electrical activity, abdominal compressions
      resulted in higher 24-h survival, but not hospital discharge rate, when compared
      with standard CPR. In animal studies ACD CPR produced increased CPP, end-tidal
      carbon dioxide, minute ventilation, and short-term survival. Subsequently
      performed clinical studies confirmed the data from the laboratory investigations;
      however, the hemodynamic advantage of ACD CPR did not result in increased long
      term survival and a better neurological outcome in both in- and out-of-hospital
      cardiac arrest patients. To date, the reason why better hemodynamic variables did
      not result in better outcomes is unknown. A combination of ACD CPR with
      interposed abdominal compressions raised cerebral blood flow by approximately
      60%, but did not augment myocardial blood flow in comparison with standard CPR.
      Recently, a device was developed to administer phased chest and abdominal
      compression-decompression CPR; this technique has been tested in an animal study
      and showed significant hemodynamic advantages and better survival compared with
      standard CPR. Clinical investigations of this device are being performed. In
      summary, since the rediscovery of chest compressions more than 35 years ago, this
      intervention has not changed significantly. Objective data from laboratory and
      clinical studies such as systolic blood pressure, CPP, and the gold standard for
      the efficacy of CPR, long-term survival and neurological outcome, will determine
      if a new device or technique can replace standard-CPR. Despite the new
      developments, it is mandatory to perform standard CPR correctly with a chest
      compression rate of 80-100/min and a depth of 38-50 mm.

PMID- 9163268
TI  - [What is the state of neuroanesthesia?].

PMID- 9163269
TI  - [The "TAS-Analyzer"].

PMID- 9163270
TI  - [Intra- and postoperative catheter epidural analgesia. Combination of epidural
      analgesia and general anesthesia].

PMID- 9163271
TI  - [BSE and heparin and gelatin preparations].

PMID- 9163272
TI  - [Clearing up the epidural blood patch].

PMID- 9163273
TI  - [S-(+)-Ketamine--today and tomorrow].

PMID- 9163274
TI  - [Effects of ketamine on CNS-function].
AB  - The present review summarises the main actions of racemic ketamine and ketamine
      enantiomers on central nervous system receptors. The primary CNS action of
      ketamine appears to be a non-competitive block of N-methyl-D-aspartate receptors.
      Although numerous other receptors (e.g., GABA, nicotinic acetylcholine, opiate,
      voltage-operated channels) have been reported to interact with ketamine, their
      role in inducing dissociative anaesthesia is still under discussion. In humans,
      characteristic electroencephalographic (EEG) changes after administration of
      ketamine are dose-dependent increases in delta, theta, and beta power. In
      equipotent doses S-(+)-ketamine induces similar EEG changes. However, in
      comparison to racemic ketamine and S-(+)-ketamine, R-(-)-ketamine does not
      suppress the EEG to the same extent. Former studies suggested that ketamine is a
      proconvulsive agent; however, recent studies have demonstrated anticonvulsive and
      even neuroprotective properties. In humans, low-dose ketamine has no influence on
      early cortical peaks of somatosensory evoked potentials (SEP). Larger doses
      induce increases in SEP amplitude while latencies are unchanged. Recent data
      indicate that analgesia induced by low-dose ketamine may be quantitated by
      specific pain-related SEP. Significant reductions of pain-induced cortical
      potentials may be correlated with subjective pain ratings. Brain-stem auditory
      evoked potentials (AEP) are not influenced by ketamine. Interestingly, in
      contrast to many other anaesthetics, middle-latency AEP were not altered by
      racemic and S-(+)-ketamine. This observation may indicate insufficient
      suppression of auditory stimulus processing during ketamine anaesthesia. Motor
      evoked responses to transcranial electrical or magnetic stimulation in humans are
      not markedly suppressed by ketamine.

PMID- 9163275
TI  - [Clinical significance of S-(+)-ketamine].
AB  - Among anaesthetic drugs, ketamine occupies a special position. biochemically,
      ketamine is a racemate consisting of equal shares of two optical enantiomers.
      Pharmacological investigations show differences between those enantiomers in both
      qualitative and quantitative properties. Furthermore, clinical superiority of S
      (+)-ketamine has been described in different therapeutic studies with regard to
      anaesthetic potency, the extent of analgesia, effects and side effects during and
      after the operation, and undiserable psychological dysfunction. On a
      neuropharmacological basis, the clinical superiority of S-(+)-ketamine is due to
      its effect on NMDA receptors in central nervous tissue, opioid receptors on both
      central and peripheral levels, and noradrenergic, dopaminergic, and
      serotoninergic mechanisms. The main problems associated with the ketamine
      racemate in clinical use are desirable psychological dysfunction and a prolonged
      period of arousal. There are grounds for the assumption that the use of S-(+)
      ketamine will minimise those problems without reducing anaesthetic potency or
      restricting the advantages of ketamine anaesthesia.

PMID- 9163276
TI  - [Endocrine reactions following S-(+)-ketamine].
AB  - ANAESTHETICS, ENDOCRINE SYSTEM, AND STRESS: The effects of anaesthetics on the
      nervous system are invariably associated with endocrine reactions, which are of
      great importance for the general characterization of anaesthetics or anaesthetic
      regimens. In this context, the endocrine stress response is mainly represented by
      adrenaline (A), noradrenaline (NA), antidiuretic hormone/vasopressin (ADH),
      adrenocorticotropic hormone (ACTH), and cortisol. PHARMACOLOGICAL PROFILE AND
      ANAESTHETIC ACTION OF KETAMINE: The pharmacological profile of ketamine is
      characterized by the term "dissociative anaesthesia." At the present time, the
      anaesthetic action of ketamine cannot be explained by a single mechanism. Its
      overall action might be due to different central and peripheral factors, and
      stereospecific effects are obvious. ENDOCRINE RESPONSES TO RACEMIC KETAMINE AND
      S(+)-KETAMINE: In contrast to stereospecific differences in the anaesthetic
      action of racemic ketamine and S-(+)-ketamine, the endocrine reactions to the S
      (+) isomer and the racemic mixture are very similar. When S(+)-ketamine is used
      as the sole anaesthetic, significant activation of the sympathoadrenergic system
      with increases in plasma levels of A and NA can be observed. This effect is
      mitigated by midazolam. In combination with propofol, sympathoadrenergic
      responsiveness is preserved without overwhelming effects. In contrast to
      monoanaesthesia with S(+)-ketamine, during combination with midazolam and
      propofol significant increases in plasma ADH levels are observed, which might be
      due to suppressed sympathoadrenergic reactivity. In addition, surgical stress
      activates the pituitary-adrenocortical system with increases in ACTH and
      cortisol. Effects of midazolam and propofol on this effect are similar. SYNOPSIS
      AND CLINICAL ASPECTS: S-(+)-ketamine as a monoanaesthetic has significant
      sympathomimetic properties, which are beneficial during induction of patients in
      shock and patients with asthma. The combination of S-(+)-ketamine and midazolam
      has weaker sympathomimetic and general endocrine-stimulating properties, and can
      be used for analgosedation in patients with cardiovascular instability and
      exogenous catecholamine requirements. In combination with propofol, the
      sympathomimetic and general endocrine-stimulating effects of S-(+)-ketamine are
      less pronounced because of contrasting properties of both drugs. This combination
      might be useful in patients with endocrine deficits and for analgosedation, when
      rapid recovery is necessary and negative circulatory effects should be avoided.

PMID- 9163277
TI  - [Recovery and psychomimetic reactions following S-(+)-ketamine].
AB  - Ketamine is a racemic mixture containing equal parts of S-(+)-ketamine and R-(-)
      ketamine. Their potency relation is approximately 4:1. In early human studies S
      (+)-ketamine was presumed to produce the desired anaesthetic effects and R-(-)
      ketamine the undesired psychic emergence reactions. Therefore, ketamine was
      compared in a number of randomised studies in volunteers and patients with
      racemic ketamine. This review addresses the impact of S-(+)-ketamine on recovery
      from anaesthesia, incidence and content of vivid dreams, and other side effects.
      The dose relation applied in the studies was 1:2. With only one exception, the
      recovery phase was clearly shorter after S-(+)-ketamine compared to racemic
      ketamine irrespective of its application as a single bolus, a bolus followed by
      continuous infusion, or an intramuscular injection. However, the incidence of
      psychic emergence reactions was lower after S-(+)-ketamine in only a single
      study. In conclusion, S-(+)-ketamine should be always combined with a hypnotic or
      sedative drug in clinical anaesthesia.

PMID- 9163278
TI  - [S-(+)-Ketamine and circulation].
AB  - The S-(+) isomer of ketamine has about twice the analgesic potency of the
      clinically used racemic mixture. Therefore, the known side effects may be reduced
      when one-half of the usual dose is administered. Several prospective, randomised,
      and double-blinded studies have been performed to assess whether the S-(+) isomer
      of ketamine is superior to the racemic mixture with respect to circulatory side
      effects. Studies in young, healthy volunteers showed that heart rate (HR) and
      arterial blood pressure (ABP) rise significantly after injection of 2 mg/kg
      ketamine racemate and 1 mg/kg S-(+) isomer without any significant difference
      between groups. In the study of Doenicke et al. plasma levels of adrenaline (A)
      were higher in the racemate group, whereas no difference was found in elevated
      plasma levels of noradrenaline (NA). Premedication with midazolam blunted major
      haemodynamic changes. The investigation of Adams et al. confirmed that HR and ABP
      rise significantly after injection of 2 mg/kg ketamine racemate and 1 mg/kg S-(+)
      isomer without any significant difference between groups. In this study, no
      differences were found between groups concerning elevated plasma levels of A and
      NA. A further study in healthy volunteers also showed comparable haemodynamic
      changes following i.m.injection of 1.0 mg/kg ketamine racemate or 0.5 mg/kg S-(+)
      isomer without any significant difference between groups. In a previous clinical
      study including 40 elderly patients undergoing elective orthopaedic surgery,
      total intravenous anaesthesia (TIVA) was performed with S-(+)-ketamine or
      ketamine racemate as an analgesic compound. For induction of TIVA, patients
      received 0.1 mg/kg midazolam and 1 mg/kg S-(+)-ketamine or 2 mg/kg racemic
      ketamine, respectively. Throughout surgery, a continuous infusion of 2 mg/kg per
      hour S-(+)-ketamine or 4 mg/kg racemic ketamine was administered. Three patients
      in the racemate group showed severe arterial hypertension after induction of
      anaesthesia and were withdrawn from the study. In both groups plasma A and NA
      levels as well as HR and ABP increased significantly. In our own randomised,
      double-blinded study, haemodynamic effects of 2 mg/kg S-(+)-ketamine and 4 mg/kg
      ketamine racemate, respectively, were investigated in 14 patients undergoing
      elective aorto-coronary bypass surgery. In both groups HR and ABP significantly
      increased in 3 patients, each although all patients were deeply sedated with
      midazolam. One patient in the S-(+)-ketamine group showed severe arterial
      hypertension and tachycardia after induction of anaesthesia and was withdrawn
      from the study. With respect to haemodynamic changes, the pharmacodynamic effects
      of ketamine racemate and S-(+)-ketamine are comparable. Therefore, it can be
      concluded that neither ketamine nor S-(+)-ketamine should be used in patients who
      suffer, e.g., from arterial hypertension and coronary artery disease.

PMID- 9163279
TI  - [Neuroprotection by ketamine at the cellular level].
AB  - A key question in cellular neuroprotection is how pharmacologic agents may
      protect neurons when applied after injury in clinically relevant concentrations.
      Of special importance is the N-methyl-D-aspartate (NMDA) antagonist ketamine,
      which offers the potential for regulation of intracellular calcium levels and
      pathophysiological NO induction by blocking excessive NMDA-receptor stimulation.
      This may reduce progressive neuronal degeneration and cell death. Initial
      evidence for ketamine's neuroprotective effects came from cell culture studies
      demonstrating increased neuronal and astroglial viability, preserved cellular
      morphology, and reduced cell swelling subsequent to anoxia-hypoxia or glutamate
      injury and ketamine application. Moreover, ketamine was found to protect cellular
      energy status after ischaemic insults and maintained ATP production, glucose
      metabolism, and mitochondrial transmembrane potentials. Subsequent studies have
      revealed ketamine's regulating effects on intracellular ion homeostasis, thus
      stabilising neuronal electrophysiological functions. In addition, ketamine was
      reported to maintain a glutamate-associated induction of intrinsic-neuronal
      protective nerve growth factors, and recent evidence suggests that S(+)-ketamine
      has a greater neuroprotective potential than ketamine racemate. S(+)-ketamine
      demonstrated a unique neuroregenerative potential that was associated with
      greater re-outgrowth of axonal neurites after mechanical injury and increased
      expression of growth-associated proteins after glutamate damage. S(+)-ketamine
      has a two- to four-fold higher affinity for the phencyclidine receptor of the
      NMDA receptor complex than ketamine racemate, and it is conceivable that the
      induction of a differentiated pattern of genes induces cellular growth activities
      via ketamine-mediated NMDA-receptor activation or blockade. However, further
      investigations elucidating ketamine's effects in animals and humans have to be
      performed before final decisions regarding a potential application of ketamine as
      a neuroprotective agent in the clinical setting can be made.

PMID- 9163280
TI  - [Ketamine racemate and S-(+)-ketamine. Cerebrovascular effects and
      neuroprotection following focal ischemia].
AB  - The phencyclidine derivative ketamine is a non-competitive N-methyl-D-aspartate
      (NMDA) receptor antagonist with the thalamo-neocortical projection system as the
      primary site of action. Racemic ketamine consists of the enantiomers S(+)
      ketamine and R(-)-ketamine. Racemic ketamine has never been considered an
      adequate anaesthetic agent in neurosurgical patients since it produces regionally
      specific stimulation of cerebral metabolism (CMRO2) and increases cerebral blood
      flow (CBF) and intracranial pressure (ICP). However, recent experiments suggest
      that both tracemic ketamine and S(+)-ketamine may reduce infarct size in animal
      models of incomplete cerebral ischaemia and brain injury. This experimental
      protective effect appears to be related to decreases in Ca++ influx and
      maintenance of brain tissue magnesium levels due to NMDA and quisqualate receptor
      blockade by ketamine. Studies in dogs have shown that racemic ketamine (2.0
      mg/kg) increases CBF in the presence of the cerebral vasodilator N2O. In
      contrast, studies in rats without background anaesthesia showed increases in CBF
      after racemic ketamine (100 mg/kg i.p.). This suggests that the cerebrovascular
      effects of racemic ketamine are related to the pre-existing cerebrovascular tone
      induced by background anaesthetics. Cerebrovascular CO2 reactivity was maintained
      regardless of the baseline cerebrovascular resistance. There are several
      mechanisms by which racemic ketamine may increase CBF. It induces dose-dependent
      respiratory depression with consequent mild hypercapnia in spontaneously
      ventilating subjects. This produces vasodilation due to the intact
      cerebrovascular CO2 reactivity. Racemic ketamine also induces regional
      neuroexcitation, which leads to stimulation of cerebral glucose consumption in
      the limbic, extrapyramidal, auditory, and sensory-motor systems. This regional
      neuroexcitation with increased CMRO2 produces increases in CBF that can be
      blocked by infusion of barbiturates or benzodiazepines. However, increases in CBF
      with racemic ketamine (1 mg/kg) may also occur during normocapnia and without
      changes in CMRO2. This effect is related to some additional direct cerebral
      vasodilating potency of racemic ketamine based on a mechanism involving blockade
      of Ca++ channels. The effects of racemic ketamine on CBF autoregulation have not
      been investigated systematically. However, studies in rats have shown that CBF
      autoregulation was maintained with low- and high-dose S(+)-ketamine. Infusion of
      racemic ketamine alters intracranial volume and ICP. Studies in spontaneously
      ventilating pigs with and without intracranial hypertension have shown that
      racemic ketamine (0.5-5.0 mg/kg) produces increases in PaCO2 and ICP. In
      contrast, identical experiments with mechanical ventilation and controlled PaCO2
      showed no changes in ICP following racemic ketamine infusion. This implies that
      increases in ICP are related to inadequate ventilation with consecutive
      hypercapnia and increases in intracranial blood volume. However, mechanical
      ventilation may not be sufficient to control ICP following racemic ketamine.
      Experiments in mechanically ventilated dogs indicate that racemic ketamine (2
      mg/kg) increases cerebral blood volume and ICP even in the presence of
      normoventilation, a response that is reversible by hyperventilation or the
      administration of diazepam. Studies in patients have shown that racemic ketamine
      (2.0 mg/kg) reduces CBF in the presence of cerebral vasodilators like halothane
      or N2O. In contrast, studies in unanaesthetised humans showed increases in CBF
      after racemic ketamine (2-3 mg/kg). This observation is consistent with animal
      studies and suggests that the cerebrovascular effects of racemic ketamine are
      related to the pre-existing cerebrovascular tone induced by background
      anaesthetics. Studies in humans with and without intracranial pathology confirm
      the data from animal experiments. (ABSTRACT TRUNCATED)

PMID- 9163281
TI  - [Effect of ketamine on global cerebral ischemia].
AB  - This review focuses on the significance of S-(+)-ketamine as a neuroprotective
      agent. Evidence in the literature supporting or contradicting a neuroprotective
      or even therapeutic role of ketamine in global cerebral ischaemia is critically
      reviewed, and data from an ongoing study in a rat global cerebral ischaemia model
      (15 min ischaemia with S(+)-ketamine administered 15 min after reperfusion) are
      reported. The number of experimental studies available so far limited, however,
      and therefore results cannot be considered conclusive at the present time. Only
      at higher ketamine dosages was protection found reliably, especially in models of
      complete forebrain ischaemia lasting over 10 min. In our own study, only after 90
      mg/kg S(+)-ketamine was there significantly better preservation of cortical
      neurons than without treatment; 30 and 60 mg/kg did not produce this effect.

PMID- 9163282
TI  - [Ketamine and neuroprotection. Clinical outlook].
AB  - As the mechanism of action of ketamine, particularly its non-competitive
      antagonism at the N-methyl-D-aspartate receptor (NMDA), has become better
      understood, the use of the drug as a neuroprotective agent has received
      increasing interest. Although the potential prometabolic effects of ketamine
      might be counterproductive to neuroprotection, the increase in intracranial
      pressure it has repeatedly been reported to produce does not appear to be
      relevant clinically under certain conditions, e.g. in patients with normocapnia
      and a stable blood pressure. Also, the drug has been shown to be anticonvulsant
      in clinically applied doses rather than epileptogenic, as was previously assumed.
      These insights have opened up entirely new perspectives for the use of ketamine
      as a neuroprotective agent. But as both in vitro and in vivo studies are
      inconclusive, the benefits of the drug are still controversial. In addition, the
      potential neurotoxicity attributed to extremely high ketamine doses is poorly
      understood. Consequently, well controlled animal experiments and studies in
      humans would be necessary to establish the role of ketamine and its more potent
      enantiomer S-(+)-ketamine in combination with other neuroprotective measures and
      to shed light on its true neuroprotective potential and its possible
      neuroregenerative effects.

PMID- 9163283
TI  - [Mechanisms of action of ketamine].
AB  - Although ketamine has been in clinical use for 3 decades, the
      neuropharmacological basis of its analgesic, anaesthetic, sympathomimetic, and
      psychotomimetic effects is still a subject of controversial discussion and
      intensive investigational efforts. In recent years, however, new experimental
      approaches to its effects on the cellular and molecular level and the
      availability of pure ketamine enantiomers contributed substantially to the
      understanding of its complex neuropharmacology. This article reviews the current
      knowledge of ketamine effects on ligand-operated and voltage-operated
      transmembrane ion channels, G-protein-coupled receptors, transmitter uptake, and
      the NO-cGMP system in neurons. With regard to its potential clinical relevance
      and supposed relative role among the complex mechanisms involved in pain
      perception, analgesia, anaesthesia, and psychotomimesis, the contributions of
      recent experimental and clinical findings to the identification of major target
      sites of ketamine are summarised. In contrast to the uncertainty surrounding the
      potential role of opioid receptors, there is now considerable evidence that NMDA
      antagonism is a central mechanism that contributes to the amnesic, analgesic,
      anaesthetic, and psychotomimetic as well as the neuroprotective actions of
      ketamine. Moreover, the involvement of non-NMDA glutamate receptors, muscarinic
      and nicotinic cholinergic transmission, interactions with 5-HT receptors, and L
      Type Ca2+ channels may account for some of its anaesthetic and neuroprotective
      properties.

PMID- 9163284
TI  - In-hospital resuscitation: executive summary.

PMID- 9163285
TI  - Transjugular intrahepatic portosystemic shunts compared with endoscopic
      sclerotherapy for the prevention of recurrent variceal hemorrhage. A randomized,
      controlled trial.
AB  - BACKGROUND: Transjugular intrahepatic portosystemic shunts (TIPS) have widened
      the use of portal decompression as therapy for variceal hemorrhage. However, no
      controlled studies have examined the efficacy of TIPS compared with that of other
      treatments. OBJECTIVE: To compare the efficacy and safety of TIPS with those of
      endoscopic sclerotherapy for the prevention of recurrent variceal hemorrhage.
      DESIGN: Randomized, controlled trial. SETTING: Tertiary-care academic medical
      center. PATIENTS: 100 patients with cirrhosis were evaluated a mean of
      approximately 10 days after an episode of acute variceal bleeding; 20 patients
      were excluded because of portal venous thrombosis (n = 6), hepatoma (n = 3),
      florid alcoholic hepatitis (n = 6), and refusal to give consent (n = 5).
      INTERVENTIONS: TIPS (n = 41) or sclerotherapy (n = 39). The latter was performed
      by freehand injections of 5% Na morrhuate at 2- to 3-week intervals. Recurrent
      variceal hemorrhage was managed by sclerotherapy followed by angiographic
      assessment of TIPS and dilatation of the stents (TIPS group) or crossover to TIPS
      (sclerotherapy group). MEASUREMENTS: Rebleeding and survival were the primary end
      points. Complications and rates of rehospitalization were secondary end points.
      RESULTS: During a mean follow-up of approximately 1000 days, recurrent
      gastrointestinal bleeding resulted from variceal hemorrhage (9 patients in the
      TIPS group and 8 in the sclerotherapy group), portal gastropathy (1 patient in
      each group), and gastric lipoma (0 and 1 patients, respectively). A higher
      mortality rate was seen with TIPS (P = 0.03). Death resulted from variceal
      bleeding (5 patients in the TIPS group and 3 in the sclerotherapy group), sepsis
      (3 and 2 patients, respectively), liver failure (2 patients in each group),
      hepatoma (1 and 0 patients, respectively), and hemoperitoneum (1 and 0 patients,
      respectively). Encephalopathy was the most common complication in the TIPS group
      (n = 12), and pain developing after sclerotherapy was the most common in the
      sclerotherapy group (n = 10). The two groups had similar rates of
      rehospitalization. CONCLUSIONS: Endoscopic sclerotherapy and TIPS are equivalent
      with respect to rebleeding developing over the long term. However, sclerotherapy
      may be superior to TIPS with respect to survival.

PMID- 9163286
TI  - Endoscopic sclerotherapy compared with percutaneous transjugular intrahepatic
      portosystemic shunt after initial sclerotherapy in patients with acute variceal
      hemorrhage. A randomized, controlled trial.
AB  - BACKGROUND: Hemorrhage from esophageal varices remains a substantial management
      problem. Endoscopic sclerotherapy was preferred for more than a decade, but
      fluoroscopically placed intrahepatic portosystemic stents have recently been used
      with increasing frequency. OBJECTIVE: To compare sclerotherapy with transjugular
      intrahepatic portosystemic shunt (TIPS) in patients with bleeding from esophageal
      varices. DESIGN: Randomized, controlled clinical trial. SETTING: Three teaching
      hospitals. PATIENTS: 49 adults hospitalized with acute variceal hemorrhage from
      November 1991 to December 1995: 25 assigned to sclerotherapy and 24 assigned to
      TIPS. INTERVENTION: Patients assigned to repeated sclerotherapy had the procedure
      weekly. In those assigned to TIPS, an expandable mesh stent was fluoroscopically
      placed between an intrahepatic portal vein and an adjacent hepatic vein.
      MEASUREMENTS: Pretreatment measures included demographic and laboratory data.
      Postrandomization data included index hospitalization survival, duration of
      follow-up, successful obliteration of varices, rebleeding from varices, number of
      variceal rebleeding events, total days of hospitalization for variceal bleeding,
      blood transfusion requirements after randomization, prevalence of encephalopathy,
      and total health care costs. RESULTS: Mean follow-up (+/-SE) was 567 +/- 104 days
      in the sclerotherapy group and 575 +/- 109 days in the TIPS group. Varices were
      obliterated more reliably by TIPS than by sclerotherapy (P < 0.001). Patients
      having TIPS were significantly less likely to rebleed from esophageal varices
      than patients receiving sclerotherapy (3 of 24 compared with 12 of 25; P =
      0.012). No other follow-up measures differed significantly between groups. A
      trend toward improved survival, which was not statistically significant, was
      noted in the TIPS group (hazard ratio, 0.53 [95% CI, 0.18 to 1.5]). CONCLUSIONS:
      In obliterating varices and reducing rebleeding events from esophageal varies,
      TIPS was more effective than sclerotherapy. However, TIPS did not decrease
      morbidity after randomization or improve health care costs. It seemed to produce
      better survival, but the increase in survival was not statistically significant.

PMID- 9163287
TI  - Prevalence of antineutrophil cytoplasmic antibodies in a large inception cohort
      of patients with connective tissue disease.
AB  - BACKGROUND: Two types of antineutrophil cytoplasmic antibodies (ANCA),
      antiproteinase 3 antibodies (anti-PR3) and antimyeloperoxidase antibodies (anti
      MPO), are useful in the diagnosis of such types of vasculitis as Wegener
      granulomatosis and microscopic polyangiitis. Connective tissue diseases
      frequently appear in the differential diagnosis of this spectrum of vasculitis.
      OBJECTIVE: To determine the prevalence of ANCA in patients with connective tissue
      disease. DESIGN: Blinded, controlled study of a 5-year inception cohort. SETTING:
      Tertiary-care university teaching hospitals. PATIENTS: 70 patients with
      rheumatoid arthritis, 70 patients with systemic lupus erythematosus, 45 patients
      with scleroderma, 36 patients with inflammatory myositis, 44 patients with the
      sjogren syndrome, 33 patients with the antiphospholipid syndrome, and 165
      patients with early undifferentiated connective tissue disease (EUCTD). Serum was
      taken from 200 blood donors and 52 patients who had known vasculitis and positive
      results on tests for anti-PR3 or anti-MPO; these patients served as controls.
      MEASUREMENTS: The presence of anti-PR3 and anti-MPO was determined by combining
      the results of indirect immunofluorescence tests for cytoplasmic (C-ANCA) and
      perinuclear (P-ANCA) patterns with the results of enzymelinked immunosorbent
      assays (ELISAs) directed to measure antigen. RESULTS: Cytoplasmic ANCA was not
      detected in any study or control patient. Perinuclear ANCA was commonly detected
      among patients with lupus (31%) but was uncommon among patients in other groups
      (0% to 5%). In all cases, P-ANCA was associated with the presence of antinuclear
      antibodies. Atypical ANCA immunofluorescence patterns were fairly common in all
      groups (11% to 39%). Antiproteinase 3 was detected by ELISA in study patients (1
      patient with rheumatoid arthritis, 1 with lupus, 1 with polymyositis, and 6 with
      EUCTD). Antimyeloperoxidase was detected by ELISA in 2 study patients (1 with
      rheumatoid arthritis and 1 with lupus). None of the patients with positive ELISA
      results had evidence of renal vasculitis during follow-up. When an ANCA scoring
      system that combines immunofluorescence and ELISA was used, the test specificity
      for vasculitis was 99.5% among patients with connective tissue disease.
      CONCLUSIONS: Patients with connective tissue disease are known to develop
      multiple autoantibodies; positivity for anti-PR3 and anti-MPO ANCA in such
      patients is highly specific for anti-PR3. However, P-ANCA immunofluorescence,
      which may have positive results because of the presence of antinuclear
      antibodies, is not a specific marker of anti-MPO. A rigorous ANCA testing system
      that combines the results of immunofluorescence with those of ELISA is highly
      specific for Wegener granulomatosis and related vasculitides even in patients
      with connective tissue disease.

PMID- 9163288
TI  - Influence of hepatitis G virus infection on the severity of liver disease and
      response to interferon-alpha in patients with chronic hepatitis C.
AB  - BACKGROUND: Dual infection with hepatitis G virus (HGV) and hepatitis C virus
      (HCV) is common. The effect of HGV infection on chronic hepatitis C is not well
      known. OBJECTIVE: To assess the prevalence of HGV infection; the effect of HGV
      infection on the clinical, virologic and histologic features of patients with
      chronic hepatitis C treated with interferon-alpha; and the influence of HGV
      infection on response to interferon-alpha therapy. DESIGN: Retrospective study.
      SETTING: A university hospital in France. PATIENTS: 228 patients with chronic
      hepatitis C treated with interferon-alpha (3 million U or 5 million U
      subcutaneously 3 times a week for 3, 6, or 12 months). MEASUREMENTS: Before
      initiation of treatment, serum HGV RNA and serum HCV RNA were detected with
      branched-DNA assays and HCV genotype was determined with a line probe assay.
      Serum HGV RNA and serum HCV RNA were detected by polymerase chain reaction at the
      end of treatment and 6 months after treatment. RESULTS: Infection with HGV was
      detected in 21% of patients and 32% of intravenous drug users. The median serum
      HGV RNA level was 33 x 10(6) genome equivalents/mL. Infection with HGV was more
      frequently found in men with a history of intravenous drug use and was associated
      with HCV genotype 3a (P = 0.02) independent of the source of infection. Serum HCV
      RNA levels, liver histologic findings, and response to interferon-alpha therapy
      did not differ between patients with and those without HGV infection. The loss of
      serum HGV RNA was not correlated with the biochemical response contrarily to the
      loss of serum HCV RNA. CONCLUSIONS: Infection with HGV occurred frequently in
      this sample of patients with chronic hepatitis C, especially in patients infected
      with HCV genotype 3a. The level of HGV viremia was high relative to the level of
      HCV viremia. Infection with HGV did not influence the severity of liver disease
      or response to interferon-alpha therapy.

PMID- 9163290
TI  - Using systematic reviews in clinical education.
AB  - Traditional educational methods change clinical practice only with considerable
      effort and difficulty. In particular, the teaching of critical appraisal in the
      setting of journal clubs does not increase the amount of medical research read by
      trainees. Experiential learning theory, corroborated by the success of problem
      based learning, encourages us to link learning to the numerous medical questions
      that physicians generate while providing patient care. Systematic reviews can
      link these questions with the results of research that would otherwise be
      difficult to locate, read, and appraise. Systematic reviews are a uniquely
      powerful mechanism for teaching, and they offer teachers a new opportunity to
      model rational and effective use of information. Systematic reviews should be
      made available at clinical sites for use during "teachable moments." Resistance
      to the use of systematic reviews can be reduced by using existing journal clubs
      to teach about the strengths and limitations of these reviews. The point that
      systematic reviews are meant to assist, not replace, clinical decision making
      deserves emphasis in such teaching.

PMID- 9163289
TI  - Complete sustained response of a refractory, post-transplantation, large B-cell
      lymphoma to an anti-CD22 immunotoxin.

PMID- 9163291
TI  - Learning from our patients: one participant's impact on clinical trial research
      and informed consent.
AB  - This Perspective includes an essay on modifying phase I clinical trials, written
      by George Zimmer, who was a professor of English and a commentary on that essay.
      Professor Zimmer was a cancer patient who participated in the phase I clinical
      trial program at the University of Chicago. His ideas are eloquently expressed
      and have had a profound effect on our investigational research for anticancer
      agents. Although at times his suggestions may seem radical, Professor Zimmer
      urges us to reconsider the 50-year-old Nuremberg paradigm that participants in
      human research are ignorant and vulnerable and must be protected. Although we
      must protect patients who have life-threatening diseases from coercive
      inducements and misplaced hopes, we must also listen carefully and thoughtfully
      to our patients. This is particularly true when, as research participants in the
      face of sacrifice and the threat of a life-ending diagnosis, they have made the
      effort to express their concerns. With the effect of the acquired
      immunodeficiency syndrome movement on clinical studies and on drug research and
      development, a precedent has been set that allows patients to reshape their role
      as participants in research trials. On a personal level, the essay by Professor
      Zimmer has had a significant effect on our research methods and, indeed, the
      focus of our research efforts. Thus, it is with a sense of respect and honor that
      we share George Zimmer's thoughts and our comments about the influence he has had
      on our research practices.

PMID- 9163292
TI  - Hospitals and Civil Rights, 1945-1963: the case of Simkins v Moses H. Cone
      Memorial Hospital.
AB  - In the 1960s, the legacy of discrimination against black persons still existed in
      all areas of medicine. This historical analysis investigates the strategies that
      were used by lawyers alongside physicians, dentists, and patients in elevating
      health care for black persons. Primary resources include oral histories,
      government documents, hospital records, archival and personal manuscripts, and
      professional and hospital periodicals. After World War II, leaders in the black
      community were determined to improve health care for black persons by ending
      discrimination in hospital policies and practices. Leaders of professional
      organizations developed a collaborative strategy that involved the court system,
      federal legislation, and research and education of the public and health
      professionals to integrate the hospital system rather than to expand the existing
      separate-but-equal system. Efforts culminated in the case of Simkins v Moses H.
      Cone Memorial Hospital; this case became the landmark decision by the U.S.
      Supreme Court and led to the elimination of segregated health care. Three months
      after the case, President Johnson ratified the Civil Rights Act of 1964, which
      included Title VI, thus extending the policy of equality to all federal programs.
      Laying a foundation for universal access to health care in the United States
      depended on a victory in the courts, in national health legislation, and in
      public opinion. All were achieved through strategic efforts to amass widespread
      support for the elimination of discrimination in medicine.

PMID- 9163293
TI  - Transjugular intrahepatic portosystemic shunts versus sclerotherapy: a discussion
      of discordant results.

PMID- 9163294
TI  - Discrimination in health care.

PMID- 9163295
TI  - Is hypertriglyceridemia a risk factor for atherosclerotic cardiovascular disease?
      A simple question with a complicated answer.

PMID- 9163296
TI  - Splenectomy for relapsing thrombotic thrombocytopenic purpura.

PMID- 9163297
TI  - The Pemberton and Maroni signs.

PMID- 9163298
TI  - The Pemberton and Maroni signs.

PMID- 9163299
TI  - Hypolipidemic drugs in coronary artery disease.

PMID- 9163300
TI  - Hypolipidemic drugs in coronary artery disease.

PMID- 9163301
TI  - High-dose chemotherapy for breast cancer.

PMID- 9163302
TI  - High-dose chemotherapy for breast cancer.

PMID- 9163303
TI  - The botulism hazard.

PMID- 9163304
TI  - Preoperative echocardiography for noncardiac surgery.

PMID- 9163305
TI  - Preoperative echocardiography for noncardiac surgery.

PMID- 9163306
TI  - Aortic valve endocarditis with Whipple disease.

PMID- 9163307
TI  - Grapefruit juice for the pruritus of cholestatic liver disease.

PMID- 9163308
TI  - Helping physicians recognize bedside rationing.

PMID- 9163309
TI  - Helping physicians recognize bedside rationing.

PMID- 9163310
TI  - Health care in America: an intimate glimpse.

PMID- 9163311
TI  - Alienation and imagination: the literature of exclusion.

PMID- 9163312
TI  - A sodium channel model.

PMID- 9163313
TI  - Identification of ligand-binding sites that form external mouth of ion pore in
      calcium and sodium channels.

PMID- 9163315
TI  - Cerebellar long-term depression enabled by nitric oxide, a diffusible
      intercellular messenger.

PMID- 9163314
TI  - Action and binding of calcium channel blockers on the putative calcium channel of
      synaptosomal plasma membrane from the electric organ of Narke japonica.

PMID- 9163316
TI  - Induction of TRE and CRE binding activities in cultured granule cells stimulated
      via glutamate receptors.

PMID- 9163317
TI  - The College of American Pathologists, 1946-1996: membership and its benefits.

PMID- 9163320
TI  - A nonsense mutation in the 3-hydroxy-3-methylglutaryl-CoA lyase gene produces
      exon skipping in two patients of different origin with 3-hydroxy-3-methylglutaryl
      CoA lyase deficiency.
AB  - A novel nonsense mutation associated with the skipping of constitutive exon 2 of
      the 3-hydroxy-3-methylglutaryl-CoA lyase gene was found in two patients, from
      Portugal and Morocco, with 3-hydroxy-3-methylglutaric acidemia. By reverse
      transcriptase PCR and single-strand conformational polymorphism a G-T
      transversion was located, at nucleotide 109, of the 3-hydroxy-3-methylglutaryl
      CoA lyase cDNA, within exon 2. Two mRNAs were produced as a result of this
      nonsense mutation: one of the expected size that contains the premature stop
      codon UAA, and the other with a deletion of 84 bp corresponding to the whole of
      exon 2. This deletion produced the loss of the last seven amino acids of the
      leader peptide and the first 21 amino acids of the mature protein. The nonsense
      mutation was found in a purine-rich GGAAG sequence, which is equal to, or similar
      to, others reported to be exonic splicing enhancers (ESE). We suggest that the
      nonsense mutation may affect a possible ESE on exon 2, which would hinder the
      splice site selection and facilitate an aberrant splice with the skipping of this
      exon. Determination by quantitative PCR shows that the ratio of mRNA with the
      nonsense mutation to the mRNA with the deletion is approx. 3:1.

PMID- 9163318
TI  - Mitogen-activated protein kinase phosphatase 1 inhibits the stimulation of gene
      expression by hypertrophic agonists in cardiac myocytes.
AB  - The effect of constitutive expression of mitogen-activated protein kinase (MAPK)
      phosphatase 1 (MKP-1) on gene expression in response to hypertrophic agonists was
      examined in cultured neonatal rat ventricular myocytes. Luciferase (LUX) reporter
      genes linked to promoters for atrial natriuretic factor, ventricular myosin light
      chain 2, beta-myosin heavy chain, skeletal muscle alpha-actin (SkM alpha-actin)
      and serum response element-regulated c-fos (c-fos-SRE) were transfected into
      cardiomyocytes. Phenylephrine (PE; 10 microM), phorbol 12-myristate 13-acetate (1
      microM) and endothelin 1 (10 nM) stimulated the expression of these various
      reporter genes by 2. 5-20-fold. MKP-1 inhibited these effects by 60-85%. In
      contrast, MKP-1 had no effect on the expression of a constitutively active Rous
      sarcoma virus-LUX reporter gene. A catalytically inactive mutant MKP-1CS
      (cysteine-->serine mutation) and the broad-specificity protein tyrosine
      phosphatase 1B (PTP-1B) had no significant effect on any reporter gene tested.
      MKP-1 had much less effect on the morphological features accompanying agonist
      induced cardiac hypertrophy. PE (10 microM) increased myocyte area by 59% but
      this effect was only decreased by one-third by MKP-1 and was also partly
      decreased (by 25%) by expression of PTP-1B. PE also altered cell shape but this
      was unaffected by MKP-1. There was also no clear effect of MKP-1 on the
      organization of the contractile apparatus into sarcomeric structures in the
      presence of 10 microM PE. We conclude that the transcriptional responses
      accompanying cardiac myocyte hypertrophy are dependent on an MKP-1-sensitive
      step, presumably the activation of one or members of the MAPK family, but that
      cell size, shape and myofibrillar organization are much less sensitive to
      inhibition by MKP-1.

PMID- 9163319
TI  - Rat basophilic leukaemia (RBL) cells overexpressing Rab3a have a reversible block
      in antigen-stimulated exocytosis.
AB  - The rat basophilic leukaemia (RBL) cell line has been widely used as a convenient
      model system to study regulated secretion in mast cells. Activation of these
      cells through the high-affinity receptor for IgE (Fcepsilon-RI) results in
      degranulation and the extracellular release of mediators. There is good evidence
      of a role for GTPases in mast cell degranulation, and a number of studies with
      peptides derived from the Rab3a effector domain have suggested that Rab3a may
      function in this process. However, in neuroendocrine cells, overexpression of
      Rab3a can act as a negative regulator of stimulated exocytosis [Holz, Brondyk,
      Senter, Kuizon and Macara (1994) J. Biol. Chem. 269, 10229-10234; Johanes, Lledo,
      Roa, Vincent, Henry and Darchen (1994) EMBO J. 13, 2029-2037]. In order to study
      the function of Rab3a in RBL degranulation, we have generated clones of RBL cells
      stably expressing Rab3a, and show that in these haematopoietic cells Rab3a can
      also function as a negative regulator of exocytosis. Overexpression of a mutant
      form of Rab3a (Asn-135 to Ile), which is predicted to be predominantly GTP-bound,
      also inhibited degranulation. However, overexpression of a mutant form of Rab3a
      that was truncated at the C-terminus to remove the sites for geranylgeranylation
      failed to inhibit degranulation. The effect of Rab3a is specific to secretion,
      and we observe no effect of Rab3a on receptor-mediated endocytosis. The Rab3a
      induced block in degranulation can be bypassed by stimulation of streptolysin-O
      permeabilized cells with guanosine 5'-[gamma-thio]triphosphate. We conclude from
      these studies that Rab3a is implicated in an early stage of granule targeting,
      whereas fusion of granules with the plasma membrane is regulated by a distinct
      downstream GTP-binding protein or proteins.

PMID- 9163321
TI  - pH-dependent DNA cleavage in permeabilized human fibroblasts.
AB  - In several cell types, apoptosis is associated with intracellular acidification
      and activation of a pH-dependent endonuclease. We have examined the effect of
      acidic pH on the DNA of permeabilized human fibroblasts, and observed cleavage of
      DNA into high-molecular-mass fragments. This pH-dependent DNA breakage was
      modulated by temperature, the presence of histones and diethyl pyrocarbonate.
      Superoxide dismutase and chelators with high affinity for Cu prevented DNA
      fragmentation, whereas catalase, DMSO and Desferal (desferrioxamine mesylate)
      offered no protection. Fragmentation of DNA into high-molecular-mass fragments,
      which is occasionally observed as an early phase of apoptosis, is thought to
      result from the activation of endonuclease(s). Our results suggest that such
      fragmentation also occurs through induction of copper-mediated site-specific DNA
      damage that is enhanced by intracellular acidification.

PMID- 9163322
TI  - Selective inhibition of mitochondrial respiration and glycolysis in human
      leukaemic leucocytes by methylglyoxal.
AB  - The effect of methylglyoxal on the oxygen consumption of mitochondria of both
      normal and leukaemic leucocytes was tested by using different respiratory
      substrates and complex specific artificial electron donors and inhibitors. The
      results indicate that methylglyoxal strongly inhibits mitochondrial respiration
      in leukaemic leucocytes, whereas, at a much higher concentration, methylglyoxal
      fails to inhibit mitochondrial respiration in normal leucocytes. Methylglyoxal
      strongly inhibits ADP-stimulated alpha-oxoglutarate and malate plus NAD+
      dependent respiration, whereas, at a higher concentration, methylglyoxal fails to
      inhibit succinate and alpha-glycerophosphate-dependent respiration. Methylglyoxal
      also fails to inhibit respiration which is initiated by duroquinone and cannot
      inhibit oxygen consumption when the N,N,N', N'-tetramethyl-p-phenylenediamine by
      pass is used. NADH oxidation by sub-mitochondrial particles of leukaemic
      leucocytes is also inhibited by methylglyoxal. Lactaldehyde, a catabolite of
      methylglyoxal, can exert a protective effect on the inhibition of leukaemic
      leucocyte mitochondrial respiration by methylglyoxal. Methylglyoxal also inhibits
      l-lactic acid formation by intact leukaemic leucocytes and critically reduces the
      ATP level of these cells, whereas methylglyoxal has no effect on normal
      leucocytes. We conclude that methylglyoxal inhibits glycolysis and the electron
      flow through mitochondrial complex I of leukaemic leucocytes. This is strikingly
      similar to our previous studies on mitochondrial respiration, glycolysis and ATP
      levels in Ehrlich ascites carcinoma cells [Ray, Dutta, Halder and Ray (1994)
      Biochem. J. 303, 69-72; Halder, Ray and Ray (1993) Int. J. Cancer 54, 443-449],
      which strongly suggests that the inhibition of electron flow through complex I of
      the mitochondrial respiratory chain and inhibition of glycolysis by methylglyoxal
      may be common characteristics of all malignant cells.

PMID- 9163323
TI  - A zinc-dependent DNA-binding activity co-operates with cAMP-responsive-element
      binding protein to activate the human thyroglobulin enhancer.
AB  - Footprinting experiments involving the human thyroglobulin gene enhancer and
      thyroid nuclear extracts revealed a protected region called X2, containing an
      incomplete cAMP-responsive element (CRE). Band-shift experiments identified two
      binding activities recognizing the X2 element: a CRE-binding protein
      (CREB)/activating transcription factor (ATF) relative that binds the half CRE
      motif and a second factor that interacts with a G-rich motif located just
      upstream from the CRE. The first factor appears to be CREB itself, as indicated
      by the supershifting when using an antibody directed against CREB, and the second
      DNA-binding activity involved was shown to be zinc-dependent and exhibited an
      apparent molecular mass of 42-44 kDa in South-Western blotting experiments. This
      factor may represent a novel entity, which we named CAF, for 'CREB Associated
      Factor'. Three copies of X2 sequence conferred a strong cAMP-dependent
      transcriptional activation to a heterologous promoter in transient transfection
      assay in cAMP-stimulated primary thyrocytes and HeLa cells. Transfection
      experiments of constructs containing the X2 element mutated in either the CRE or
      the G-rich site showed that both motifs were required for this transcription
      activating function. Moreover, the combination of several individual X2 elements
      mutated in either the CRE or the G-rich motif did not exhibit full
      transcriptional activity. This suggests that, in the context of the X2 element,
      CREB requires a close interaction with CAF to achieve both basal and cAMP
      dependent transcriptional activation.

PMID- 9163324
TI  - Down-regulation of beta3-adrenergic receptor expression in rat adipose tissue
      during the fasted/fed transition: evidence for a role of insulin.
AB  - The beta3-adrenergic receptor (beta3-AR) exerts a central role in the
      transduction of catecholamine effects in white and brown adipose tissue (WAT and
      BAT). A recent report has documented that insulin strongly down-regulates beta3
      AR expression and catecholamine responsiveness in 3T3-F442A adipocytes [Feve, El
      Hadri, Quignard-Boulange and Pairault (1994) Proc. Natl. Acad. Sci. U.S.A. 91,
      5677-5681]. In the present report we show that the rise in plasma insulin levels
      elicited by the fasted/fed transition is associated with a reduction in beta3-AR
      mRNA levels and beta-adrenergic responsiveness in WAT and BAT. beta3-AR
      transcripts are also decreased in adipose tissue from animals subjected for 6 h
      to euglycaemic hyperinsulinaemic glucose clamps. Moreover, insulin acts directly
      on cultured rat white and brown adipocytes to decrease beta3-AR gene expression
      and adenylate cyclase activity in response to beta3-AR-selective agonists. These
      results suggest that there is a close relationship between food intake, plasma
      insulin levels and beta3-AR expression.

PMID- 9163326
TI  - Activation of cGMP-stimulated phosphodiesterase by nitroprusside limits cAMP
      accumulation in human platelets: effects on platelet aggregation.
AB  - cGMP enhances cAMP accumulation in platelets via cGMP-inhibited phosphodiesterase
      (PDE3) [Maurice and Haslam (1990) Mol. Pharmacol. 37, 671-681]. However, cGMP
      might also limit cAMP accumulation by activating cGMP-stimulated
      phosphodiesterase (PDE2). We therefore evaluated the role of PDE2 in human
      platelets by using erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) to inhibit this
      enzyme selectively. IC50 values for the inhibition of platelet PDE2 by EHNA, with
      10 microM cAMP as substrate in the absence and in the presence of 1 microM cGMP,
      were 15 and 3 microM respectively. Changes in platelet cyclic [3H]nucleotides
      were measured after prelabelling with [3H]adenine and [3H]guanine. Nitroprusside
      (NP) caused concentration-dependent increases in [3H]cGMP and a biphasic increase
      in [3H]cAMP, which was maximal at 10 microM (49+/-6%) and smaller at 100 microM
      (32+/-6%) (means+/-S.E.). In the presence of EHNA (20 microM), which had no
      effects alone, NP caused much larger increases in platelet [3H]cAMP (125+/-14% at
      100 microM). EHNA also enhanced [3H]cGMP accumulation at high NP concentrations.
      In accord with these results, EHNA markedly potentiated the inhibition of
      thrombin-induced platelet aggregation by NP. The roles of cAMP and cGMP in this
      effect were investigated by using 2', 5'-dideoxyadenosine to inhibit adenylate
      cyclase. This compound decreased the accumulation of [3H]cAMP but not that of
      [3H]cGMP, and diminished the inhibition of platelet aggregation by NP with EHNA.
      We conclude that much of the effect of NP with EHNA is mediated by cAMP.
      Lixazinone (1 microM), a selective inhibitor of PDE3, increased platelet [3H]cAMP
      by 177+/-15%. This increase in [3H]cAMP was markedly inhibited by NP; EHNA
      blocked this effect of NP. Parallel studies showed that NP suppressed the
      inhibition of platelet aggregation by lixazinone. EHNA enhanced the large
      increases in [3H]cAMP seen with 20 nM prostacyclin (PGI2), but had no effect with
      1 nM PGI2. NP and 1 nM PGI2 acted synergistically to increase [3H]cAMP, an effect
      attributable to the inhibition of PDE3 by cGMP; EHNA greatly potentiated this
      synergism. In contrast, NP decreased the [3H]cAMP accumulation seen with 20 nM
      PGI2, an effect that was blocked by EHNA. The results show that, provided that
      cGMP is present, PDE2 plays a major role in the hydrolysis of low cAMP
      concentrations and restricts any increases in cAMP concentration and decreases in
      platelet aggregation caused by the inhibition of PDE3. At high cAMP, PDE2 plays
      the major role in cAMP breakdown, whether cGMP is present or not.

PMID- 9163325
TI  - Cloning, sequencing and expression of rat liver 3-phosphoglycerate dehydrogenase.
AB  - Rat liver d-3-phosphoglycerate dehydrogenase was purified to homogeneity and
      digested with trypsin, and the sequences of two peptides were determined. This
      sequence information was used to screen a rat hepatoma cDNA library. Among 11
      positive clones, two covered the whole coding sequence. The deduced amino acid
      sequence (533 residues; Mr 56493) shared closer similarity with Bacillus subtilis
      3-phosphoglycerate dehydrogenase than with the enzymes from Escherichia coli,
      Haemophilus influenzae and Saccharomyces cerevisiae. In all cases the similarity
      was most apparent in the substrate- and NAD+-binding domains, and low or
      insignificant in the C-terminal domain. A corresponding 2.1 kb mRNA was present
      in rat tissues including kidney, brain and testis, whatever the dietary status,
      and also in livers of animals fed a protein-free, carbohydrate-rich diet, but not
      in livers of control rats, suggesting transcriptional regulation. The full-length
      rat 3-phosphoglycerate dehydrogenase was expressed in E. coli and purified. The
      recombinant enzyme and the protein purified from liver displayed hyperbolic
      kinetics with respect to 3-phosphoglycerate, NAD+ and NADH, but substrate
      inhibition by 3-phosphohydroxypyruvate was observed; this inhibition was
      antagonized by salts. Similar properties were observed with a truncated form of 3
      phosphoglycerate dehydrogenase lacking the C-terminal domain, indicating that the
      latter is not implicated in substrate inhibition or in salt effects. By contrast
      with the bacterial enzyme, rat 3-phosphoglycerate dehydrogenase did not catalyse
      the reduction of 2-oxoglutarate, indicating that this enzyme is not involved in
      human D- or L-hydroxyglutaric aciduria.

PMID- 9163327
TI  - ATP synthase subunit c expression: physiological regulation of the P1 and P2
      genes.
AB  - Pre-translational regulation of subunit c has been suggested to control the
      biosynthesis of mitochondrial ATP synthase (ATPase) in brown adipose tissue
      (BAT). Subunit c is encoded by the genes P1 and P2, which encode identical mature
      proteins. We have determined here the levels of P1 and P2 mRNAs in different
      tissues, in response to cold acclimation in rats, during ontogenic development of
      BAT in hamsters, and following thyroid hormone treatment in rat BAT and liver.
      Quantitative ribonuclease protection analysis showed that both the P1 and P2
      mRNAs were present in all rat tissues measured. Their total amount in each tissue
      corresponded well with the ATPase content of that tissue. While the P1/P2 mRNA
      ratio is high in ATPase-rich tissues, the P2 mRNA dominates in tissues with less
      ATPase. Cold acclimation affects P1 but not P2 gene expression in rat BAT. A
      rapid and transient increase in P1 mRNA is followed by sustained depression,
      which is accompanied by a decrease in ATPase content. Similarly, ontogenic
      suppression of ATPase content in hamster BAT was accompanied by suppression of
      the P1 mRNA levels, while P2 expression was virtually unchanged. Furthermore,
      when hypothyroid rats were treated with thyroid hormone, the steady-state level
      of P1 but not of P2 mRNA was significantly increased in liver. BAT was
      unaffected. We conclude that the P1 and P2 genes for subunit c are differentially
      regulated in vivo. While the P2 gene is expressed constitutively, the P1 gene
      responds to different physiological stimuli as a means of modulating the relative
      content of ATP synthase.

PMID- 9163328
TI  - Requirement of gamma-carboxyglutamic acid residues for the biological activity of
      Gas6: contribution of endogenous Gas6 to the proliferation of vascular smooth
      muscle cells.
AB  - Gas6 (encoded by growth-arrest-specific gene 6) is a gamma-carboxyglutamic acid
      (Gla)-containing protein which is released from growth-arrested vascular smooth
      muscle cells (VSMCs) and potentiates VSMC proliferation induced by Ca2+
      mobilizing growth factors, but not that induced by receptor tyrosine kinases. In
      this study we examined the importance of Gla residues for the biological
      activities of Gas6 and tried to assess the importance of endogenous Gas6 in VSMC
      proliferation. We demonstrated that Gla-deficient Gas6 lacked receptor-binding
      and growth-potentiating activities. Therefore the vitamin K-dependent
      modification of Gas6 appeared to be essential for its biological activities. Next
      we used warfarin, an inhibitor of vitamin K-dependent gamma-carboxylation, to
      estimate the contribution of endogenous Gas6 to VSMC proliferation. Warfarin
      markedly inhibited the thrombin-induced proliferation of VSMC without affecting
      the mRNA or protein expression of Gas6. Therefore the inhibition seems to be due
      to prevention of the vitamin K-dependent modification of Gas6. However, warfarin
      did not affect epidermal growth factor-induced proliferation. A neutralizing
      antibody against Gas6 gave a similar result, i.e. it inhibited thrombin-induced
      VSMC proliferation but not that induced by epidermal growth factor. These results
      indicate that endogenously produced Gas6 is very important for VSMC proliferation
      induced by Ca2+-mobilizing growth factors.

PMID- 9163329
TI  - Structure of a truncated human surfactant protein D is less effective in
      agglutinating bacteria than the native structure and fails to inhibit
      haemagglutination by influenza A virus.
AB  - Surfactant protein D (SP-D) is a lung-specific protein that is synthesized and
      secreted by lung epithelial cells and is believed to play an important role in
      lung host defence. This protein belongs to the C-type lectin family, which is
      characterized by an N-terminal cysteine-rich domain, a collagen-like domain, a
      neck domain and a carbohydrate recognition domain (CRD). To elucidate the
      biological actions of this animal lectin against such pathogens as micro
      organisms, the biological activities of a recombinant partial SP-D lacking a
      collagen-like domain were examined. A recombinant human SP-D, consisting of a
      short collagen region (two repeats of Gly-Xaa-Yaa amino acid sequences), the neck
      domain and the CRD, was expressed in Escherichia coli. The recombinant SP-D was
      purified on a nickel column and then on a maltose-agarose column. This protein
      can form a trimeric structure owing to the neck domain and exhibits sugar-binding
      activity and specificity similar to those of native human SP-D. The recombinant
      SP-D caused dose-dependent and calcium-dependent agglutination of E. coli Y1088.
      The agglutination titre (the concentration required to achieve a 50% decrease in
      light transmission by agglutination) of recombinant SP-D was approx. 6-fold that
      of native SP-D. As for conglutination, the recombinant trimeric conglutinin
      required 8-16-fold higher concentrations than the native counterpart. In
      haemagglutination inhibition (HI) of influenza A virus, although native and
      recombinant conglutinin showed similar levels of HI activity, the recombinant SP
      D was unable to inhibit haemagglutination, even at a concentration approx. 120
      fold that of the native SP-D. The lectin precipitation and lectin blot assays
      showed that the truncated SP-D could bind to influenza A virus as well as native
      SP-D did. These results indicate that the agglutination activity of trimeric
      collectins can be largely retained, and furthermore that the oligomeric structure
      with several hands at opposite sites can enhance agglutination activity. The
      difference in HI activity against influenza A virus between native and
      recombinant SP-D suggests that SP-D uses a different mechanism from that of
      conglutinin to inhibit viral haemagglutination.

PMID- 9163331
TI  - Bivalent cations stabilize yeast alcohol dehydrogenase I.
AB  - The thermostability of yeast alcohol dehydrogenase (ADH) I is strongly dependent
      on the presence of NaCl, a salt that is almost neutral on the Hofmeister scale,
      which suggests that solvent-accessible electrostatic repulsion might play a role
      in the inactivation of the enzyme. Moreover, CaCl2 and MgCl2 are able to
      stabilize the enzyme at millimolar concentrations. Ca2+ stabilizes yeast ADH I by
      preventing the dissociation of the reduced form of the enzyme and by preventing
      the unfolding of the oxidized form of the enzyme. An analysis of several
      chimaeric ADHs suggests that Ca2+ is fixed by the Asp-236 and Glu-101 side chains
      in yeast ADH I, but that Ca2+ can be displaced by replacing Met-168 by an Arg
      residue, as suggested by a three-dimensional model of the enzyme structure. These
      results indicate that electrostatic repulsion can cause protein unfolding and/or
      dissociation. It is proposed that yeast ADH I binds Mg2+ in vivo.

PMID- 9163330
TI  - Involvement of disulphide bonds in the renal sodium/phosphate co-transporter NaPi
      2.
AB  - The rat renal brush border membrane sodium/phosphate co-transporter NaPi-2 was
      analysed in Western blots with polyclonal antibodies raised against its N
      terminal and C-terminal segments. Under reducing conditions, proteins of 45-49
      and 70-90 kDa (p45 and p70) were detected with N-terminal antibodies, and
      proteins of 40 and 70-90 kDa (p40 and p70) were detected with C-terminal
      antibodies. p40 and p45 apparently result from a post-translational cleavage of
      NaPi-2 but remain linked through one or more disulphide bonds. Glycosidase
      digestion showed that both polypeptides are glycosylated; the cleavage site could
      thus be located between Asn-298 and Asn-328, which have been shown to constitute
      the only two N-glycosylated residues in NaPi-2. In the absence of reducing
      agents, both N-terminal and C-terminal antibodies detected p70 and a protein of
      180 kDa (p180), suggesting the presence of p70 dimers. Much higher concentrations
      of beta-mercaptoethanol were required to produce a given effect in intact
      membrane vesicles than in solubilized proteins, indicating that the affected
      disulphide bonds are not exposed at the surface of the co-transporter. Phosphate
      transport activity decreased with increasing concentrations of reducing agents
      [beta-mercaptoethanol, dithiothreitol and tris-(2-carboxyethyl)phosphine] and was
      linearly correlated with the amount of p180 detected. The target sizes estimated
      from the radiation-induced loss of intensity of p40, p70 and p180 were all
      approx. 190 kDa, suggesting that NaPi-2 exists as an oligomeric protein in which
      the subunits are sufficiently close to one another to allow substantial energy
      transfer between the monomers. When protein samples were pretreated with beta
      mercaptoethanol [2.5% and 5% (v/v) to optimize the detection of p40 and p70]
      before irradiation, target sizes estimated from the radiation-induced loss of
      intensity of p40 and p70 were 74 and 92 kDa respectively, showing the presence of
      disulphide bridges in the molecular structure of NaPi-2.

PMID- 9163332
TI  - Regulation of N-linked core glycosylation: use of a site-directed mutagenesis
      approach to identify Asn-Xaa-Ser/Thr sequons that are poor oligosaccharide
      acceptors.
AB  - N-linked glycosylation can profoundly affect protein expression and function. N
      linked glycosylation usually occurs at the sequon Asn-Xaa-Ser/Thr, where Xaa is
      any amino acid residue except Pro. However, many Asn-Xaa-Ser/Thr sequons are
      glycosylated inefficiently or not at all for reasons that are poorly understood.
      We have used a site-directed mutagenesis approach to examine how the Xaa and
      hydroxy (Ser/Thr) amino acid residues in sequons influence core-glycosylation
      efficiency. We recently demonstrated that certain Xaa amino acids inhibit core
      glycosylation of the sequon, Asn37-Xaa-Ser, in rabies virus glycoprotein (RGP).
      Here we examine the impact of different Xaa residues on core-glycosylation
      efficiency when the Ser residue in this sequon is replaced with Thr. The core
      glycosylation efficiencies of RGP variants with different Asn37-Xaa-Ser/Thr
      sequons were compared by using a cell-free translation/glycosylation system.
      Using this approach we confirm that four Asn-Xaa-Ser sequons are poor
      oligosaccharide acceptors: Asn-Trp-Ser, Asn-Asp-Ser, Asn-Glu-Ser and Asn-Leu-Ser.
      In contrast, Asn-Xaa-Thr sequons are efficiently glycosylated, even when Xaa=Trp,
      Asp, Glu or Leu. A comparison of the glycosylation status of Asn-Xaa-Ser and Asn
      Xaa-Thr sequons in other glycoproteins confirms that sequons with Xaa=Trp, Asp,
      Glu or Leu are rarely glycosylated when Ser is the hydroxy amino acid residue,
      and that these sequons are unlikely to serve as glycosylation sites when
      introduced into proteins by site-directed mutagenesis.

PMID- 9163333
TI  - Regulation by bivalent cations of phospholipid binding to the C2A domain of
      synaptotagmin III.
AB  - Synaptotagmins are Ca2+-and phospholipid-binding proteins of synaptic vesicles
      that might function as Ca2+ receptors for neurotransmitter release via their
      first C2 (C2A) domain. Here we describe the effect of Mg2+ on phospholipid
      binding to the C2A domains of multiple synaptotagmins (II-VI), and demonstrate
      that only synaptotagmin III can bind negatively charged phospholipids
      [phosphatidylserine (PS) and phosphatidylinositol] in a Mg2+-dependent manner.
      The Mg2+-dependent interaction with PS was found to have an EC50 of approx. 30
      microM Mg2+, which is comparable to that of Sr2+ and Ba2+ (EC50 values of approx.
      10 microM). This binding property of the C2A domain is specific to synaptotagmin
      III, because none of the C2A domains of other proteins, such as rabphilin 3A,
      Doc2alpha, Doc2beta or Gap1(m), showed phospholipid binding activity in the
      presence of 1 mM Mg2+. Our results suggest that synaptotagmin III is involved in
      presynaptic functions different from those of synaptotagmins I and II.

PMID- 9163335
TI  - Identification and distribution of proteins in isolated endosomal fractions of
      rat liver: involvement in endocytosis, recycling and transcytosis.
AB  - 1. The polypeptides of the three endosomal fractions isolated from livers of
      oestradiol-treated rats were analysed by two-dimensional gel electrophoresis.
      Silver-stained gels revealed that although the three endosomal fractions shared a
      generally similar pattern of approx. 120 components, qualitative and quantitative
      differences between the three endocytic fractions could be demonstrated. 2. The
      'early' endosomes [compartment of uncoupling of receptors and ligands (CURL)]
      comprised the most complex fraction and contained most of the polypeptides found
      in the 'late' endosomes [multivesicular bodies (MVBs)] and the receptor recycling
      compartment (RRC). When CURL was analysed by two-dimensional gel electrophoresis
      after partition with Triton X-114, it showed the largest number of integral
      membrane polypeptides. 3. Some of the major receptors (polymeric immunoglobulin
      receptor, transferrin receptor, low-density lipoprotein receptor,
      asialoglycoprotein receptor, beta1-integrin, mannose 6-phosphate receptor,
      epidermal growth factor receptor and AGp110) and internalized ligands (IgA, IgG,
      albumin, haptoglobin, transferrin and alpha2-macroglobulin) were further studied
      by Western blotting. 4. The distribution of the identified receptors and ligands
      among the three endosomal fractions was in agreement with their expected
      functionalities. 5. The polypeptide composition of the bile was also examined and
      compared with ligands and proteins identified in the different endocytic
      fractions. 6. Finally, an electron microscopy study confirms the distinctive
      physical and ultrastructural features of the three isolated endosomal fractions.

PMID- 9163334
TI  - Characterization of the substrate specificity of the major cysteine protease
      (cruzipain) from Trypanosoma cruzi using a portion-mixing combinatorial library
      and fluorogenic peptides.
AB  - The substrate specificity of the major cysteinyl proteinase of the parasitic
      protozoan Trypanosoma cruzi (cruzipain) was investigated, by combinatorial
      replacement of amino acid residues at positions P5-P'5, using a fluorescent
      quenched solid-phase library assay. Positively charged residues appear to be a
      general preference in the P5-P3 and the P'5-P'3 positions, while a hydrophobic
      residue was always required at the P2 position. A broad range of amino acids
      could be accepted at the P'1 position. A clear difference in terms of specificity
      between cruzipain and human cathepsin L was observed for the accommodation of Pro
      at the P2 position. The P1 specificity was investigated by a more detailed enzyme
      kinetic analysis using peptidyl-MCA (where MCA is methylcoumarin amide) and Abz
      peptidyl-EDDnp [where Abz is o-aminobenzoic acid and EDDnp is N-(2,4
      dinitrophenyl)ethylenediamine] as substrates, and the results were compared with
      those obtained using human cathepsin L. Cruzipain showed a clear preference for
      benzyl-Cys or Arg at the P1 position. Human cathepsin L presented similar
      behaviour to that of cruzipain for the hydrolysis of the epsilon-NH2-Cap-Leu-Xaa
      MCA (where Cap is epsilon-aminocaproyl) and Abz-Lys-Leu-Xaa-Phe-Ser-Lys-Gln-EDDnp
      series, whereas the mammalian enzyme was able to tolerate large P1 residues, such
      as phenylalanine, better than cruzipain in the latter series.

PMID- 9163336
TI  - Endoplasmic reticulum Ca2+ is important for the proteolytic processing and
      intracellular transport of proinsulin in the pancreatic beta-cell.
AB  - The role of intracellular Ca2+ in the proteolytic processing and intracellular
      transport of secretory granule proproteins was investigated by pulse-chase
      radiolabelling of isolated rat islets of Langerhans. The conversion of proinsulin
      was inhibited by depletion of medium Ca2+ with EGTA and by blocking the transport
      of Ca2+ into cells with the Ca2+-channel antagonists verapamil, nifedipine and
      NiCl2. Proinsulin conversion was also reduced by the endoplasmic reticulum Ca2+
      ATPase inhibitor thapsigargin, indicating that the process requires transport of
      Ca2+ into the endoplasmic reticulum. This was supported by the finding that
      proinsulin processing was inhibited when Ca2+ was depleted before or during pulse
      labelling, but not after transport of the protein to post-endoplasmic-reticulum
      compartments. Similarly, the inhibition of proinsulin processing was reversed by
      re-introduction of medium Ca2+ around the time of radiolabelling, but not after
      15 min of chase incubation. Ca2+ depletion also decreased proteolytic maturation
      of the prohormone convertases PC1, PC2 and carboxypeptidase H. Secretion
      experiments suggested that the rate and extent of proinsulin transport into
      secretory granules were inhibited marginally by Ca2+ depletion, whereas those of
      the convertases were markedly impeded. Inhibition of proinsulin conversion by
      Ca2+ depletion was thus not simply related to the Ca2+-dependencies of mature PC1
      and PC2, but also to a requirement for endoplasmic reticulum Ca2+ in proteolytic
      maturation of the convertases and in their transfer to secretory granules. The
      results also suggest that the Ca2+ required for prohormone processing in the
      granules enters the secretory pathway via the endoplasmic reticulum.

PMID- 9163337
TI  - Diadenosine polyphosphate-stimulated gluconeogenesis in isolated rat proximal
      tubules.
AB  - Diadenosine polyphosphates released into the extracellular environment influence
      a variety of metabolic and other cellular activities in a wide range of target
      tissues. Here we have studied the impact of these novel nucleotides on
      gluconeogenesis in isolated rat proximal tubules. Gluconeogenesis was stimulated
      following exposure of isolated proximal tubules to a range of adenine-containing
      nucleotides including ADP, ATP, Ap3A, Ap4A, Ap5A and Ap6A. The concentration
      dependence of ATP-, Ap3A- and Ap4A-mediated stimulation of gluconeogenesis was
      similar and was consistent with a role for these agents in the physiological
      control of renal metabolism. Nucleotide-stimulated gluconeogenesis was diminished
      in the presence of agents that interfere with phospholipase C activation or
      intracellular Ca2+ metabolism, indicative of a role for polyphosphoinositide
      mediated Ca2+ mobilization in the mechanism of action of ATP, Ap3A and Ap4A. The
      characteristics of binding of [2-3H]Ap4A to renal plasma-membrane preparations
      suggest that Ap4A mediates its effects on proximal tubule gluconeogenesis via
      interaction with P2y-like purinoceptor(s) also recognized by extracellular ATP.

PMID- 9163338
TI  - Transgenic mice overexpressing ornithine and S-adenosylmethionine decarboxylases
      maintain a physiological polyamine homoeostasis in their tissues.
AB  - Recent work has shown that transgenic mice overexpressing human ornithine
      decarboxylase display no marked changes in the tissue concentrations of
      spermidine or spermine in spite of a dramatic increase in putrescine levels. In
      the tissues of transgenic mice carrying the human spermidine synthase gene and in
      those of hybrid mice overexpressing both ornithine decarboxylase and spermidine
      synthase, spermidine and spermine levels remain within normal limits. To test
      whether the amount of the propylamine group donor, decarboxylated S
      adenosylmethionine, limits the conversion of putrescine into the higher
      polyamines, we have produced transgenic mouse lines harbouring the rat S
      adenosylmethionine decarboxylase gene in their genome. However, neither these
      mice nor the hybrid mice overexpressing both ornithine decarboxylase and S
      adenosylmethionine decarboxylase displayed significant changes in their
      spermidine and spermine tissue levels. To study the mechanism by which cells
      maintain the constancy of the polyamine concentrations, we have determined the
      metabolic flux of polyamines in transgenic primary fibroblasts using pulse
      labelling. The results indicate that the polyamine flow is faster in transgenic
      primary fibroblasts than in non-transgenic fibroblasts and that the intracellular
      homoeostasis of higher polyamines is maintained at least partly by the
      acetylation of spermidine and spermine and their secretion into the medium.

PMID- 9163339
TI  - Rapid Ca2+ influx induced by the action of dibutylhydroquinone and glucagon in
      the perfused rat liver.
AB  - Glucagon induces a slight Ca2+ efflux when administered to the perfused rat
      liver. However, the hormone promotes rapid and significant Ca2+ influx after the
      prior administration of 2, 5-di(t-butyl)-1,4-hydroquinone (BHQ), an agent that
      promotes Ca2+ release from the endoplasmic reticulum (ER). The concentrations of
      glucagon that promote Ca2+ influx are similar to those that promote
      glycogenolysis and gluconeogenesis in isolated hepatocytes. The permeable
      analogue of cAMP, but not that of cGMP, is able to duplicate the Ca2+-mobilizing
      effects of glucagon. The influx of Ca2+ into liver is blocked by Ni2+.
      Administration of sodium azide, an inhibitor of mitochondrial electron transport,
      also blocks the BHQ plus glucagon-induced Ca2+ influx and this is reversed when
      azide administration is terminated. The actions of azide are evident within 60 s
      after administration or withdrawal, and also occur when either oligomycin or
      fructose is co-administered; this provides evidence for an effect of azide
      independent of cellular ATP depletion. Measurement of total calcium in
      mitochondria that were isolated rapidly from perfused livers after the combined
      administration of glucagon and BHQ confirmed that large quantities of
      extracellular Ca2+ had entered these organelles. These experiments provide
      evidence that in the perfused rat liver the artificial emptying of the ER Ca2+
      pool allows glucagon to promote rapid and sustained Ca2+ influx that seems to
      terminate in mitochondria.

PMID- 9163340
TI  - The amino-terminal module of the C4b-binding protein alpha-chain is crucial for
      C4b binding and factor I-cofactor function.
AB  - C4b-binding protein (C4BP) regulates the classical pathway C3-convertase of the
      complement system. Human C4BP is composed of seven identical subunits (alpha
      chains) and one unique one (beta-chain). Both types of chains contain homologous
      repeats called complement control proteins (CCPs); the alpha-chain contains eight
      CCPs and the beta-chain three. Each alpha-chain contains a binding site for C4b
      although the detailed localization of this binding site is not known. We have
      used three different chimeric proteins, originally designed to localize the
      protein S-binding site on C4BP, to demonstrate the importance of the amino
      terminal part of the alpha-chain for the complement-regulatory functions of C4BP.
      These recombinant proteins were composed of C4BP alpha-chains with one, two or
      three of the amino-terminal CCPs replaced by corresponding CCPs from the C4BP
      beta-chain. Furthermore, seven different monoclonal antibodies were raised
      against C4BP and characterized using the recombinant chimeric proteins. Whereas
      all three recombinant chimeras bind protein S with the same affinity as plasma
      purified C4BP, none of them bound to C4b. Three of the antibodies, which were
      found to bind to alpha-chain CCP 1 and CCP 2, completely inhibited the binding of
      plasma-purified C4BP to immobilized C4b. In addition, two of these antibodies
      totally blocked the factor I-cofactor activity of C4BP in a C4b-degradation
      assay. The binding site for one of the monoclonal antibodies was also studied
      using electron microscopy where it was confirmed that this antibody bound to the
      amino-terminal tip of the alpha-chain. These results show that the amino-terminal
      CCP of the C4BP alpha-chain (CCP 1) is crucial for the C4b binding and factor I
      cofactor activity.

PMID- 9163341
TI  - S-Nitrosoglutathione as a substrate for gamma-glutamyl transpeptidase.
AB  - S-Nitrosoglutathione (GSNO) has been used as a nitric oxide (.NO) donor compound
      and has also been postulated to be involved in the transport of .NO in vivo. In
      this study we have examined the possibility that GSNO is a substrate for gamma
      glutamyl transpeptidase (gamma-GT), an enzyme that hydrolyses the gamma-glutamyl
      moiety of glutathione to give glutamate and cysteinylglycine. gamma-GT
      accelerated the decomposition of GSNO, forming S-nitrosocysteinylglycine (CG-SNO)
      by a mechanism inhibitable by the gamma-GT inhibitors acivicin and S
      methylglutathione. The Km of gamma-GT for GSNO was found to be 28 microM. In the
      presence of contaminating transition metal ions, gamma-GT accelerated the release
      of ;NO from GSNO, as CG-SNO is more susceptible to transition metal ion-dependent
      decomposition than GSNO. However, in the presence of the transition metal ion
      chelator diethylenetriaminepentaacetic acid, neither GSNO nor CG-SNO decomposed
      to generate .NO. Neither S-methylglutathione nor acivicin affected the
      vasodilatory response to GSNO in an isolated perfused rat heart. However, rat
      kidney homogenate stimulated the decomposition of GSNO by an acivicin-inhibitable
      mechanism. It is likely therefore that gamma-GT is involved in the decomposition
      of GSNO in the kidney but not in the heart.

PMID- 9163342
TI  - Inhibition of bovine nasal cartilage degradation by selective matrix
      metalloproteinase inhibitors.
AB  - N-terminal analysis of aggrecan fragments lost from bovine nasal cartilage
      cultured in the presence of recombinant human interleukin 1alpha revealed a
      predominant ARGSVIL sequence with an additional ADLEX sequence. Production of the
      ARGSVIL-containing fragments has been attributed to the action of a putative
      proteinase, aggrecanase. The minor sequence (ADLEX) corresponds to a new reported
      cleavage product; comparison of this sequence with the available partial sequence
      of bovine aggrecan indicates that this is the product of a cleavage occurring
      towards the C-terminus of the protein. Matrix metalloproteinase (MMP) inhibitors
      inhibited aggrecan loss from bovine nasal explants incubated in the presence of
      recombinant human interleukin 1alpha. A strong correlation between inhibition of
      aggrecan metabolism and inhibition of stromelysin 1 (MMP 3) (r=0.93) suggests a
      role for stromelysin or a stromelysin-like enzyme in cartilage aggrecan
      metabolism. However, the compounds were approx. 1/1000 as potent in inhibiting
      aggrecan loss from the cartilage explants as they were in inhibiting stromelysin.
      There was little or no correlation between inhibition of aggrecan metabolism and
      inhibition of gelatinase B (MMP 9) or inhibition of collagenase 1 (MMP 1).
      Studies with collagenase inhibitors with a range of potencies showed a
      correlation between inhibition of collagenase activity and inhibition of collagen
      degradation in the cartilage explant assay. This indicates that in interleukin
      1alpha-driven bovine nasal cartilage destruction, stromelysin (or a closely
      related enzyme) is involved in aggrecan metabolism, whereas collagenase is
      principally responsible for collagen degradation.

PMID- 9163343
TI  - Promotion-resistant JB6 mouse epidermal cells exhibit defects in
      phosphatidylethanolamine synthesis and phorbol ester-induced phosphatidylcholine
      hydrolysis.
AB  - The tumour-promotion-sensitive (P+) and -resistant (P-) variants of mouse JB6
      epidermis-derived cells have often been used to study the requirements for the
      tumour-promoting effect of PMA. As part of an effort to identify the defect(s) in
      JB6 P- cells that might prevent the promoting effect of PMA, stimulation of
      phospholipase D (PLD)-mediated hydrolysis of phosphatidylcholine (PtdCho) and
      phosphatidylethanolamine (PtdEtn) by PMA as well as the rate of phospholipid
      synthesis were compared in three P+ variants, two P- variants and a transformed
      variant of the JB6 cell line. PMA (5-100 nM) had significantly less stimulatory
      effect on PtdCho hydrolysis in P- cells than in P+ or transformed JB6 cells. The
      effects of PMA on PtdEtn hydrolysis in the P+ and P- cell lines were similar,
      whereas in transformed cells PMA had slightly less effect. Each JB6 cell line was
      found to contain similar amounts of PtdCho. In contrast, P- cells contained
      significantly less PtdEtn and a correspondingly higher level of ethanolamine
      phosphate compared with P+ and transformed cells. P- cells also secreted
      ethanolamine phosphate into the medium; this process was greatly enhanced by PMA.
      In the two P- variants the synthesis of PtdEtn from [14C]ethanolamine was reduced
      to various extents, whereas the rate of PtdCho synthesis was comparable in each
      JB6 cell line. The synthesis of PtdCho, but not PtdEtn, was greatly stimulated by
      PMA in both the P+ and P- clones. The results indicate that decreased
      synthesis/level of PtdEtn and suboptimal functioning of a PtdCho-specific PLD are
      common characteristics of the P- JB6 cells examined so far. The observed
      alterations in phospholipid metabolism may play a role in the resistance of P-
      cells to the tumour-promoting action of PMA.

PMID- 9163344
TI  - Biosynthesis of a low-molecular-mass rat submandibular gland mucin glycoprotein
      in COS7 cells.
AB  - We have examined the biosynthesis of a low-molecular-mass mucin from rat
      submandibular gland (RSMG) expressed recombinantly in COS7 tissue culture cells,
      focusing primarily on the addition of carbohydrate to the protein core of the
      mucin. We find evidence for N-linked glycosylation, but this modification is not
      required for secretion of the mucin. Similarly, although the recombinant RSMG
      mucin, like its native counterpart, contains large amounts of O-linked
      carbohydrate, chain extension beyond the initial O-linked GalNAc moiety is not
      required for secretion. We have identified partially glycosylated mucin by a
      combination of metabolic pulse-chase and lectin precipitations of the
      biosynthetic intermediates. Our results suggest that the addition of GalNAc to
      threonine and serine in the RSMG mucin does not occur simultaneously, as has been
      described for other O-glycosylated proteins.

PMID- 9163345
TI  - Mass spectrometric analysis of rat ovary and testis cytosolic glutathione S
      transferases (GSTs): identification of a novel class-alpha GST, rGSTA6*, in rat
      testis.
AB  - Cytosolic glutathione S-transferases (GSTs) from rat ovaries and testis were
      purified by a combination of GSH and S-hexylglutathione affinity chromatography.
      The isolated GSTs were subjected to reverse-phase HPLC, electrospray MS and N
      terminal peptide sequencing analysis. The major GST isoenzymes expressed in
      ovaries are subunits A3, A4, M1, M2 and P1. Other isoenzymes detected are
      subunits A1, M3 and M6*. In rat testis, the major GST isoenzymes expressed are
      subunits A3, M1, M2, M3, M5* and M6*. Subunits A1, A4 and P1 are expressed in
      lesser amounts. We could not detect post-translational modifications of any GSTs
      with known cDNA sequence. The molecular masses of subunits M5* and M6*, two class
      Mu GSTs that have not been cloned, were determined to be 25495 and 26538 Da
      respectively. An N-terminally modified protein from rat testis with molecular
      mass 25737 Da was isolated from the S-hexylglutathione column. Results from
      internal peptide sequencing analysis indicate that this is a novel class-Alpha
      GST that has not been previously reported. We designate this protein rGSTA6*.

PMID- 9163346
TI  - Two different negative regulatory elements control the transcription of T-cell
      activation gene 3 in activated mast cells.
AB  - T-cell activation gene 3 (TCA3) encodes a beta-chemokine that is
      transcriptionally regulated in mast cells; the gene has a functional NF-kappaB
      element at positions -194 to -185. The 5'-flanking region of this gene is also
      known to have a negative regulatory region between -2057 and -1342. To
      characterize the negative regulatory elements (NREs), this region was sequenced
      and then digested by HindIII enzyme into two fragments, NRE-1 (-2057 to -1493)
      and NRE-2 (-1492 to -1342). Both NRE-1 and NRE-2 in the 5'-3' orientation
      inhibited chloramphenicol acetyltransferase (CAT)-protein synthesis by a TCA3-CAT
      construct transfected into mast cells that were then activated. Only NRE-1
      inhibited CAT-protein synthesis in the 3'-5' orientation. Further deletion of the
      5' region of NRE-1 partially abolished the inhibitory activity. Both NRE-1 and
      NRE-2 inhibited the activity of a CD20-CAT construct independent of cell
      activation. Electrophoretic mobility shift assays showed DNA-protein complex
      formation with subsequences (CCCCCATTCT) of NRE-1 (NRE-1a) and (CCATGA) of NRE-2
      (NRE-2b). NRE-1a appears to be novel. NRE-2b is identical with a putative
      silencer motif in the alphaIIb integrin gene. Site-directed mutagenesis
      demonstrated that both NRE-1a and NRE-2b are important in the negative regulation
      of TCA3 promoter activity. In vivo ligation-mediated PCR footprinting of the NRE
      2 region revealed protection between -1372 and -1354, which contains NRE-2b. The
      data thus demonstrate identity of a silencer motif, here termed NRE-2b, in both
      the alphaIIb integrin gene and the TCA3, and that this silencer region in mast
      cells is functional both in vivo and in vitro. Further, evidence is presented
      that the promoter for TCA3 contains a novel silencer motif, termed NRE-1a,
      characterized by a CT-rich sequence.

PMID- 9163347
TI  - Stimulation of mucin exocytosis from human epithelial cells by nitric oxide:
      evidence for a cGMP-dependent and a cGMP-independent pathway.
AB  - The aim of this work was to investigate the role of nitric oxide (NO) on the
      macromolecular exocytotic function of human epithelial cells. We tested the
      effects of two NO-generating drugs, i.e. 1-hexanamine 6-(2-hydroxy-1-methyl-2
      nitrosohydrazine)-N-methyl (MAHMA NONOate) and sodium nitroprusside (SNP), on
      mucin exocytosis from the human colonic epithelial HT29-Cl.16E cell line. Our
      results show that MAHMA NONOate and SNP elicited a rapid mucin exocytotic
      response through a cGMP-dependent and a cGMP-independent pathway respectively.
      Indeed, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), a newly available
      specific inhibitor of soluble guanylate cyclase, inhibited both cGMP accumulation
      and subsequent mucin exocytosis evoked by MAHMA NONOate. By contrast, SNP did not
      alter intracellular cGMP levels, and SNP-mediated mucin exocytosis was not
      inhibited by ODQ. As expected from two NO donors acting through distinct
      pathways, the combined action of MAHMA NONOate and SNP led to an additive effect
      on mucin exocytosis. SNP was likely to act through S-nitrosylation of a cellular
      target, because cysteine, a reductive thiol that provides decoy targets for SNP
      through the formation of nitrosocysteine, abolished the early stimulatory effect
      of SNP on mucin exocytosis. Finally, the fact that in the presence of cysteine
      SNP was able to trigger a late, ODQ-inhibitable, mucin exocytotic response
      demonstrates the ability of NO to shift its intracellular signalling pathway
      depending on the changes of the redox state of the milieu.

PMID- 9163349
TI  - Amino acid sequence of the alpha subunit and computer modelling of the alpha and
      beta subunits of echicetin from the venom of Echis carinatus (saw-scaled viper).
AB  - Echicetin, a heterodimeric protein from the venom of Echis carinatus, binds to
      platelet glycoprotein Ib (GPIb) and so inhibits platelet aggregation or
      agglutination induced by various platelet agonists acting via GPIb. The amino
      acid sequence of the beta subunit of echicetin has been reported and found to
      belong to the recently identified snake venom subclass of the C-type lectin
      protein family. Echicetin alpha and beta subunits were purified. N-terminal
      sequence analysis provided direct evidence that the protein purified was
      echicetin. The paper presents the complete amino acid sequence of the alpha
      subunit and computer models of the alpha and beta subunits. The sequence of alpha
      echicetin is highly similar to the alpha and beta chains of various heterodimeric
      and homodimeric C-type lectins. Neither of the fully reduced and alkylated alpha
      or beta subunits of echicetin inhibited the platelet agglutination induced by von
      Willebrand factor-ristocetin or alpha-thrombin. Earlier reports about the
      inhibitory activity of reduced and alkylated echicetin beta subunit might have
      been due to partial reduction of the protein.

PMID- 9163348
TI  - Peroxisome proliferator-induced acyl-CoA thioesterase from rat liver cytosol:
      molecular cloning and functional expression in Chinese hamster ovary cells.
AB  - We have isolated and cloned a cDNA that codes for one of the peroxisome
      proliferator-induced acyl-CoA thioesterases of rat liver. The deduced amino acid
      sequence corresponds to the major induced isoform in cytosol. Analysis and
      comparison of the deduced amino acid sequence with the established consensus
      sequences suggested that this enzyme represents a novel kind of esterase with an
      incomplete lipase serine active site motif. Analyses of mRNA and its expression
      indicated that the enzyme is significantly expressed in liver only after
      peroxisome proliferator treatment, but isoenzymes are constitutively expressed at
      high levels in testis and brain. The reported cDNA sequence is highly homologous
      to the recently cloned brain acyl-CoA thioesterase [Broustas, Larkins, Uhler and
      Hajra (1996) J. Biol. Chem. 271, 10470-10476], but subtle differences throughout
      the sequence, and distinct differences close to the resulting C-termini, suggest
      that they are different enzymes, regulated in different manners. A full-length
      cDNA clone was expressed in Chinese hamster ovary cells and the expressed enzyme
      was characterized. The palmitoyl-CoA hydrolysing activity (Vmax) was induced
      approx. 9-fold to 1 micromol/min per mg of cell protein, which was estimated to
      correspond to a specific activity of 250 micromol/min per mg of cDNA-expressed
      enzyme. Both the specific activity and the acyl-CoA chain length specificity were
      very similar to those of the purified rat liver enzyme.

PMID- 9163350
TI  - Binding of Abeta to alpha- and beta-synucleins: identification of segments in
      alpha-synuclein/NAC precursor that bind Abeta and NAC.
AB  - NAC, a 35-residue peptide derived from the neuronal protein alpha-synuclein/NAC
      precursor, is tightly associated with Abeta fibrils in Alzheimer's disease
      amyloid, and alpha-synuclein has recently been shown to bind Abeta in vitro. We
      have studied the interaction between Abeta and synucleins, aiming at determining
      segments in alpha-synuclein that can account for the binding, as well as
      identifying a possible interaction between Abeta and the beta-type synuclein. We
      report that Abeta binds to native and recombinant alpha-synuclein, and to beta
      synuclein in an SDS-sensitive interaction (IC50 approx. 20 microM), as determined
      by chemical cross-linking and solid-phase binding assays. alpha-Synuclein and
      beta-synuclein were found to stimulate Abeta-aggregation in vitro to the same
      extent. The synucleins also displayed Abeta-inhibitable binding of NAC and they
      were capable of forming dimers. Using proteolytic fragmentation of alpha
      synuclein and cross-linking to 125I-Abeta, we identified two consecutive binding
      domains (residues 1-56 and 57-97) by Edman degradation and mass spectrometric
      analysis, and a synthetic peptide comprising residues 32-57 possessed Abeta
      binding activity. To test further the possible significance in pathology, alpha
      synuclein was biotinylated and shown to bind specifically to amyloid plaques in a
      brain with Alzheimer's disease. It is proposed that the multiple Abeta-binding
      sites in alpha-synuclein are involved in the development of amyloid plaques.

PMID- 9163351
TI  - Arabinanase A from Pseudomonas fluorescens subsp. cellulosa exhibits both an endo
      and an exo- mode of action.
AB  - Pseudomonas fluorescens subsp. cellulosa expressed arabinanase activity when
      grown on media supplemented with arabinan or arabinose. Arabinanase activity was
      not induced by the inclusion of other plant structural polysaccharides, and was
      repressed by the addition of glucose. The majority of the Pseudomonas arabinanase
      activity was extracellular. Screening of a genomic library of P. fluorescens
      subsp. cellulosa DNA constructed in Lambda ZAPII, for recombinants that
      hydrolysed Red-dyed arabinan, identified five arabinan-degrading plaques. Each of
      the phage contained the same Pseudomonas arabinanase gene, designated arbA, which
      was present as a single copy in the Pseudomonas genome. The nucleotide sequence
      of arbA revealed an open reading frame of 1041 bp encoding a protein, designated
      arabinanase A (ArbA), of Mr 39438. The N-terminal sequence of ArbA exhibited
      features typical of a prokaryotic signal peptide. Analysis of the primary
      structure of ArbA indicated that, unlike most Pseudomonas plant cell wall
      hydrolases, it did not contain linker sequences or have a modular structure, but
      consisted of a single catalytic domain. Sequence comparison between the
      Pseudomonas arabinanase and proteins in the SWISS-PROT database showed that ArbA
      exhibits greatest sequence identity with arabinanase A from Aspergillus niger,
      placing the enzyme in glycosyl hydrolase Family 43. The significance of the
      differing substrate specificities of enzymes in Family 43 is discussed. ArbA
      purifed from a recombinant strain of Escherichia coli had an Mr of 34000 and an N
      terminal sequence identical to residues 32-51 of the deduced sequence of ArbA,
      and hydrolysed linear arabinan, carboxymethylarabinan and arabino
      oligosaccharides. The enzyme displayed no activity against other plant structural
      polysaccharides, including branched sugar beet arabinan. ArbA produced almost
      exclusively arabinotriose from linear arabinan and appeared to hydrolyse arabino
      oligosaccharides by successively releasing arabinotriose. ArbA and the
      Aspergillus arabinanase mediated a decrease in the viscosity of linear arabinan
      that was associated with a significant release of reducing sugar. We propose that
      ArbA is an arabinanase that exhibits both an endo- and an exo- mode of action.

PMID- 9163352
TI  - Fip-vvo, a new fungal immunomodulatory protein isolated from Volvariella
      volvacea.
AB  - A new fungal immunomodulatory protein (Fip) has been purified from the edible
      mushroom, Volvariella volvacea, and designated Fip-vvo. Analysis of the purified
      protein by SDS/PAGE followed by Coomassie Blue staining demonstrated that Fip-vvo
      is a single polypeptide with an apparent molecular mass of 15 kDa. Periodic
      acid/Schiff staining showed that this single polypeptide lacks carbohydrates.
      Using an in vitro bioassay measuring blast-formation stimulatory activity, Fip
      vvo was shown to stimulate the maximum proliferation of human peripheral blood
      lymphocytes at a concentration of 5 microg/ml. Fip-vvo was capable of
      agglutinating rat red blood cells. Neither haemagglutination nor mitogenic
      activities were inhibited by mono- or dimeric sugars. In vivo, repeat
      administration of Fip-vvo greatly reduced the production of BSA-induced Arthus
      reaction in mice, whereas little effect was observed on the prevention of
      systemic anaphylaxis reactions. The selectively enhanced transcriptional
      expression of interleukin (IL)-2, IL-4, interferon-gamma, tumour necrosis factor
      alpha, lymphotoxin and IL-2 receptor by Fip-vvo was also demonstrated by reverse
      transcriptase-PCR. This finding suggests that Fip-vvo exerts its immunomodulatory
      effects via cytokine regulation. In addition, the complete amino acid sequence of
      Fip-vvo was obtained by direct protein sequencing. This protein consists of 112
      amino acid residues with a blocked N-terminal end and has a calculated molecular
      mass of 12667 Da not including the N-terminal blocking group. By gel filtration
      analysis, Fip-vvo exhibited a molecular mass of 26 kDa for the native molecules
      in PBS. This result indicates that native Fip-vvo is most likely a non-covalently
      associated homodimeric molecule.

PMID- 9163353
TI  - Divergent effects of extracellular and intracellular alkalosis on Ca2+ entry
      pathways in vascular endothelial cells.
AB  - Modulation by alkalosis of basal leak Ca2+ entry and store-depletion-induced Ca2+
      entry was investigated in the vascular endothelial cell line ECV 304. Ca2+ entry
      was monitored as the increase in the intracellular free Ca2+ concentration
      ([Ca2+]i) induced by elevation of the extracellular Ca2+ concentration. When ECV
      304 cells were challenged with 100 nM thapsigargin in nominally Ca2+-free
      solution, [Ca2+]i increased transiently, and the increase in [Ca2+]i during a
      subsequent cumulative elevation of extracellular Ca2+ (from nominally Ca2+-free
      up to 5 mM) was markedly enhanced compared with non-stimulated cells (i.e. basal
      Ca2+ leak). Prolonged elevation of the extracellular pH (pHo) from 7.4 to 7.9 did
      not affect resting [Ca2+]i or the thapsigargin-induced [Ca2+]i transient evoked
      in nominally Ca2+-free solution, but increased leak Ca2+ entry as well as store
      depletion-activated Ca2+ entry significantly. Basal Ca2+ leak and store-depletion
      activated Ca2+ entry were enhanced either by acute elevation of pHo from 7.4 to
      7.9 or by chronic alkalosis (pHo=7.9). Stimulation of Ca2+ entry by extracellular
      alkalosis was observed both in normal and in high extracellular K+ (110 mM)
      solution, suggesting that the effects of alkalosis are independent of membrane
      potential. The intracellular pH (pHi) increased slightly during both acute and
      chronic extracellular alkalosis (from 7.22+/-0.01 to 7.37+/-0.04 and 7. 45+/-0.05
      respectively). Elevation of pHi to 7.60+/-0.06 at constant pHo by administration
      of 20 mM NH4Cl failed to stimulate, and in fact inhibited, store-depletion
      activated Ca2+ entry. Our results demonstrate that a decrease in the
      extracellular but not the intracellular proton concentration promotes both basal
      and stimulated Ca2+ entry into endothelial cells.

PMID- 9163354
TI  - Antibiotic resistance and neurotoxicity: a molecular link to neurotrophins.

PMID- 9163355
TI  - Ionotropic GABA receptor from lobster olfactory projection neurons.
AB  - This study reports an ionotropic GABA (gamma-aminobutyric acid) receptor in
      projection neurons acutely dissociated from the olfactory lobe of the brain of
      the spiny lobster and analyzed by whole cell and cell-free patch-clamp recording.
      GABA evokes a macroscopic current in the cells that is linear from -100 to + 100
      mV, reverses at the imposed chloride equilibrium potential, has a permeability
      sequence of Cl- > acetate > bicarbonate > phosphate > propionate and SCN- > Br- >
      I- > Cl- > F-, and is reversibly blocked by the Cl channel blocker picrotoxin but
      not tert-butylbicyclophosphorothionate (TBPS). The current is bicuculline
      insensitive and activated by muscimol, isoguvacine, cis-4-aminocrotonic acid
      (CACA), and trans-aminocrotonic acid (TACA), as well as by the GABA(C)-receptor
      antagonists 4,5,6,7-tetrahydroisoxazolo [5,4,-c]pyridin-3-ol (THIP), 3-amino-1
      propanesulfonic acid (3-APS), and imidazole-4-acetic acid (I-4AA), but not the
      GABA(B)-receptor agonists baclofen and 3-aminopropylphosphonic acid (3-APA).
      Agonist potency for the receptor is TACA > muscimol > GABA > I-4AA > isoguvacine
      > 3-APS > CACA > THIP. Unitary chloride currents in cell-free, outside-out
      patches from the cells share enough of these pharmacological properties to
      indicate that the channel underlies the macroscopic current. The receptor
      mediates an inhibitory current in the cells in vivo. The receptor is similar, if
      not identical, to one from neurons cultured from the thoracic ganglia of the
      clawed lobster. The more extensive pharmacological characterization of the
      receptor reported here indicates that this lobster CNS receptor is
      pharmacologically distinct from previously characterized ionotropic GABA
      receptors.

PMID- 9163356
TI  - Suppression of task-related saccades by electrical stimulation in the primate's
      frontal eye field.
AB  - Patients with frontal lobe damage have difficulty suppressing reflexive saccades
      to salient visual stimuli, indicating that frontal lobe neocortex helps to
      suppress saccades as well as to produce them. In the present study, a role for
      the frontal eye field (FEF) in suppressing saccades was demonstrated in macaque
      monkeys by application of intracortical microstimulation during the performance
      of a visually guided saccade task, a memory prosaccade task, and a memory
      antisaccade task. A train of low-intensity (20-50 microA) electrical pulses was
      applied simultaneously with the disappearance of a central fixation target, which
      was always the cue to initiate a saccade. Trials with and without stimulation
      were compared, and significantly longer saccade latencies on stimulation trials
      were considered evidence of suppression. Low-intensity stimulation suppressed
      task-related saccades at 30 of 77 sites tested. In many cases saccades were
      suppressed throughout the microstimulation period (usually 450 ms) and then
      executed shortly after the train ended. Memory-guided saccades were most
      dramatically suppressed and were often rendered hypometric, whereas visually
      guided saccades were less severely suppressed by stimulation. At 18 FEF sites,
      the suppression of saccades was the only observable effect of electrical
      stimulation. Contraversive saccades were usually more strongly suppressed than
      ipsiversive ones, and cells recorded at such purely suppressive sites commonly
      had either foveal receptive fields or postsaccadic responses. At 12 other FEF
      sites at which saccadic eye movements were elicited at low thresholds, task
      related saccades whose vectors differed from that of the electrically elicited
      saccade were suppressed by electrical stimulation. Such suppression at saccade
      sites was observed even with currents below the threshold for eliciting saccades.
      Pure suppression sites tended to be located near or in the fundus, deeper in the
      anterior bank of the arcuate than elicited saccade sites. Stimulation in the
      prefrontal association cortex anterior to FEF did not suppress saccades, nor did
      stimulation in premotor cortex posterior to FEF. These findings indicate that the
      primate FEF can help orchestrate saccadic eye movements by suppressing
      inappropriate saccade vectors as well as by selecting, specifying, and triggering
      appropriate saccades. We hypothesize that saccades could be suppressed both
      through local FEF interactions and through FEF projections to subcortical regions
      involved in maintaining fixation.

PMID- 9163357
TI  - Visuospatial properties of ventral premotor cortex.
AB  - In macaque ventral premotor cortex, we recorded the activity of neurons that
      responded to both visual and tactile stimuli. For these bimodal cells, the visual
      receptive field extended from the tactile receptive field into the adjacent
      space. Their tactile receptive fields were organized topographically, with the
      arms represented medially, the face represented in the middle, and the inside of
      the mouth represented laterally. For many neurons, both the visual and tactile
      responses were directionally selective, although many neurons also responded to
      stationary stimuli. In the awake monkeys, for 70% of bimodal neurons with a
      tactile response on the arm, the visual receptive field moved when the arm was
      moved. In contrast, for 0% the visual receptive field moved when the eye or head
      moved. Thus the visual receptive fields of most "arm + visual" cells were
      anchored to the arm, not to the eye or head. In the anesthetized monkey, the
      effect of arm position was similar. For 95% of bimodal neurons with a tactile
      response on the face, the visual receptive field moved as the head was rotated.
      In contrast, for 15% the visual receptive field moved with the eye and for 0% it
      moved with the arm. Thus the visual receptive fields of most "face + visual"
      cells were anchored to the head, not to the eye or arm. To construct a visual
      receptive field anchored to the arm, it is necessary to integrate the position of
      the arm, head, and eye. For arm + visual cells, the spontaneous activity, the
      magnitude of the visual response, and sometimes both were modulated by the
      position of the arm (37%), the head (75%), and the eye (58%). In contrast, to
      construct a visual receptive field that is anchored to the head, it is necessary
      to use the position of the eye, but not of the head or the arm. For face + visual
      cells, the spontaneous activity and/or response magnitude was modulated by the
      position of the eyes (88%), but not of the head or the arm (0%). Visual receptive
      fields anchored to the arm can encode stimulus location in "arm-centered"
      coordinates, and would be useful for guiding arm movements. Visual receptive
      fields anchored to the head can likewise encode stimuli in "head-centered"
      coordinates, useful for guiding head movements. Sixty-three percent of face +
      visual neurons responded during voluntary movements of the head. We suggest that
      "body-part-centered" coordinates provide a general solution to a problem of
      sensory-motor integration: sensory stimuli are located in a coordinate system
      anchored to a particular body part.

PMID- 9163358
TI  - Role of potassium and calcium in the generation of cellular bursts in the dentate
      gyrus.
AB  - Epileptiform activity, which appears to be endogenous, has been recorded in the
      granule cells of the dentate gyrus before the onset of synchronized seizure
      activity and has been termed cellular bursts. It has been postulated that an
      increase in input to the dentate gyrus causes a local increase in extracellular
      K+ concentration ([K+]o) and a decrease in [Ca2+]o that results in this cellular
      bursting. The first test of this hypothesis is to determine whether the cellular
      bursts appear in ionic conditions that occur in vivo before the onset of
      synchronized epileptic activity. This hypothesis was tested in vitro by varying
      the ionic concentrations in the perfusing solution and recording changes in the
      granule cells of the dentate gyrus. Intra- and extracellular recordings were made
      in the dentate gyri of hippocampal slices prepared from anesthetized adult
      Sprague-Dawley rats. Increasing the extracellular potassium or decreasing the
      extracellular calcium of the perfusing solution caused three forms of spontaneous
      activity to appear: depolarizing potentials, action potentials, and cellular
      bursts. Increasing potassium or decreasing calcium also caused the granule cells
      to depolarize and reduced their input resistance. No synchronized extracellular
      field activity was detected. Simultaneously increasing potassium and decreasing
      calcium caused cellular bursts to appear at concentrations recorded in vivo
      before the onset of synchronized reverberatory seizure activity.

PMID- 9163359
TI  - Activation and detection of facilitation as studied by presynaptic voltage
      control at the inhibitor of the crayfish opener muscle.
AB  - Facilitation at the crayfish neuromuscular inhibitor synapse was investigated
      with the use of a presynaptic voltage control method in which 5-ms presynaptic
      pulses were used to activate and monitor facilitation. A single 5-ms pulse was
      able to activate facilitation with a decay time constant similar to that of the
      F2 component of facilitation activated by action potentials. The quality of the
      control of presynaptic potential during F2 facilitation was evaluated by
      measuring the amplitude of presynaptic pulses and by analyzing the shape of the
      depolarization-release coupling plot during facilitation. Both approaches
      suggested that neither the amplitude of presynaptic depolarizations nor the space
      clamp of the presynaptic axon was changed during F2 facilitation. The activation
      of facilitation was examined by changing the amplitude of conditioning pulses
      systematically and using a test pulse of a constant amplitude to monitor
      facilitation. We found that a significant amount of facilitation could be
      activated by conditioning pulses that were subthreshold to the activation of
      transmitter release. Facilitation plateaued before the inhibitory postsynaptic
      potentials (IPSPs) activated by conditioning pulses reached their maximum. A
      double logarithm plot of facilitation magnitude against the conditioning IPSP
      amplitude yielded a slope of 0.34, which implies that the calcium ion
      cooperativity of activating facilitation is about one third of the secretion
      process. These findings enabled us to activate near maximal facilitation, by a
      burst of subthreshold conditioning pulses, without any conditioning transmitter
      release, and, therefore, to avoid complications associated with previous
      transmitter release. The detection of facilitation was examined by changing test
      pulse amplitude systematically to evaluate the ability of the test pulse to
      detect a constant level of facilitation. The magnitude of normalized facilitation
      decreased with increasing test pulse amplitude. The magnitude of absolute
      facilitation (the amplitude of the facilitated minus the control IPSP) increased
      with increasing test pulse amplitude. A double logarithm plot between facilitated
      and control IPSPs gave rise to a slope of 0.77, which suggests that the calcium
      cooperativity of transmitter release was decreased during facilitation.

PMID- 9163360
TI  - Rapid development of synaptic connections and plasticity between sensory neurons
      and motor neurons of Aplysia in cell culture: implications for learning and
      regulation of synaptic strength.
AB  - We describe here the time course of functional synapse formation and of the
      development of short-term synaptic plasticity at Aplysia sensorimotor synapses in
      cell culture, as well as the effects of blocking protein synthesis or
      postsynaptic receptors on the development of synaptic transmission and
      plasticity. We find that synaptic responses can be elicited in 50% of sensory
      neuron-motor neuron pairs by 1 h after cell contact and that short-term
      homosynaptic depression and synaptic augmentation and restoration by the
      endogenous facilitatory transmitter serotonin are present at the earliest stages
      of synapse formation. Neither block of protein synthesis with anisomycin nor
      block of two types of postsynaptic glutamate receptor has any effect on the
      development of synaptic transmission or synaptic plasticity. The rapidity of
      synapse formation and maturation and their independence of protein synthesis
      suggest that changes in the number of functional synapses could contribute to
      short- and intermediate-term forms of synaptic plasticity and learning.

PMID- 9163361
TI  - Eye-head coordination during head-unrestrained gaze shifts in rhesus monkeys.
AB  - We analyzed gaze shifts made by trained rhesus monkeys with completely
      unrestrained heads during performance of a delayed gaze shift task. Subjects made
      horizontal, vertical, and oblique gaze shifts to visual targets. We found that
      coordinated eye-head movements are characterized by a set of lawful
      relationships, and that the initial position of the eyes in the orbits and the
      direction of the gaze shift are two factors that influence these relationships.
      Head movements did not contribute to the change in gaze position during small
      gaze shifts (<20 degrees) directed along the horizontal meridian, when the eyes
      were initially centered in the orbits. For larger gaze shifts (25-90 degrees),
      the head contribution to the gaze shift increased linearly with increasing gaze
      shift amplitude, and eye movement amplitude saturated at an asymptotic amplitude
      of approximately 35 degrees. When the eyes began deviated in the orbits
      contralateral to the direction of the ensuing gaze shift, the head contributed
      less and the eyes more to amplitude-matched gaze shifts. The relative timing of
      eye and head movements was altered by initial eye position; head latency relative
      to gaze onset increased as the eyes began in more contralateral initial
      positions. The direction of the gaze shift also affected the relative amplitudes
      of eye and head movements; as gaze shifts were made in progressively more
      vertical directions, eye amplitude increased and head contribution declined
      systematically. Eye velocity was a saturating function of gaze amplitude for
      movements without a head contribution (gaze amplitude <20 degrees). As head
      contribution increased with increasing gaze amplitude (20-60 degrees), peak eye
      velocity declined by >200 degrees/s and head velocity increased by 100 degrees/s.
      For constant-amplitude eye movements (approximately 30 degrees), eye velocity
      declined as the velocity of the concurrent head movement increased. On the basis
      of these relationships, it is possible to accurately predict gaze amplitude, the
      amplitudes of the eye and head components of the gaze shift, and gaze, eye, and
      head velocities, durations and latencies if the two-dimensional displacement of
      the target and the initial position of the eyes in the orbits are known. These
      data indicate that signals related to the initial positions of the eyes in the
      orbits and the direction of the gaze shift influence separate eye and head
      movement commands. The hypothesis that this divergence of eye and head commands
      occurs downstream from the superior colliculus is supported by recent electrical
      stimulation and single-unit recording data.

PMID- 9163362
TI  - Enhancement of whole cell synaptic currents by low osmolarity and by low [NaCl]
      in rat hippocampal slices.
AB  - We recorded whole cell currents of patch-clamped neurons in stratum pyramidale of
      CA1 region of rat hippocampal tissue slices. Synaptic currents were evoked by
      orthodromic stimulation while holding potential of the neuron was varied from
      hyperpolarized to depolarized levels. Extracellular osmolarity (pi(o)) was
      lowered by superfusion with artificial cerebrospinal fluid in which NaCl
      concentration ([NaCl]) was reduced. The effect of low extracellular NaCl was
      tested in additional trials in which NaCl was substituted by isosmolar fructose.
      Both lowering of pi(o) and isosmotic lowering of extracellular [NaCl] ([NaCl]o)
      caused reversible increase of excitatory postsynaptic currents. The effect of
      lowering pi(o) was concentration dependent, and it was significantly stronger
      than the effect of equivalent isosmotic lowering of [NaCl]o. Inhibitory
      postsynaptic currents also increased in many but not in all cases. Lowering of
      pi(o) caused a prolongation of the time constant of relaxation of the capacitive
      charging current induced by small hyperpolarizing voltage steps. A virtual input
      capacitance, calculated by dividing this time constant by the input resistance,
      increased during hypotonic exposure. Isosmotic lowering of [NaCl]o had no effect
      on time constant or input capacitance. Depolarizing voltage commands evoked
      spikelike inward currents presumably representing Na+-dependent action potentials
      generated outside the voltage-clamped region of the cell. These current spikes
      became smaller in low pi(o) and in low [NaCl]o. Broader, voltage-dependent,
      presumably Ca2+-mediated inward currents became more prominent during hypotonic
      exposure. We conclude that lowering of [NaCl]o causes enhancement of excitatory
      synaptic transmission. Transmission may be facilitated by the uptake of Ca2+ into
      presynaptic terminals as well as into postsynaptic target neurons, induced by the
      low [NaCl]o. Lowering of pi(o) enhances synaptic transmission more than does a
      corresponding isosmotic lowering of [NaCl]. The excess increase recorded from the
      cell soma in low pi(o) may in part be due to changing electrotonic length caused
      by the swelling of dendrites.

PMID- 9163363
TI  - Neural tuning to sound duration in the inferior colliculus of the big brown bat,
      Eptesicus fuscus.
AB  - Neural tuning to different sound durations may be a useful filter for
      identification of certain sounds, especially those that are biologically
      important. The auditory midbrains of mammals and amphibians contain neurons that
      appear to be tuned to sound duration. In amphibians, neurons are tuned to
      durations of sound that are biologically important. The purpose of this study was
      to characterize responses of neurons in the inferior colliculus (IC) of the big
      brown bat, Eptesicus fuscus, to sounds of different durations. Our aims were to
      determine what percent of neurons are duration tuned and how best durations are
      correlated to durations of echolocation calls, and to examine response properties
      that may be relevant to the mechanism for duration tuning, such as latency and
      temporal firing pattern; we also examined frequency tuning and rate-level
      functions. We recorded from 136 single units in the central nucleus of the IC of
      unanesthetized bats. The stimuli were pure tones, frequency-modulated sweeps, and
      broadband noise. The criterion for duration tuning was an increase in spike count
      of > or = 50% at some durations compared with others. Of the total units sampled,
      36% were tuned to stimulus duration. All of these units were located in the
      caudal half of the IC. Best duration for most units ranged from < 1 to 10 ms, but
      a few had best durations up to > or = 20 ms. This range is similar to the range
      of durations of echolocation calls used by Eptesicus. All duration-tuned neurons
      responded transiently. The minimum latency was always longer than the best
      duration. Duration-tuned units have best durations and best frequencies that
      match the temporal structure and frequency range of the echolocation calls. Thus
      the results raise the hypothesis that neurons in the IC of Eptesicus, and
      probably the auditory midbrain of other vertebrates, are tuned to biologically
      important sound durations. We suggest a model for duration tuning consisting of
      three components: 1) inhibitory input that is correlated with the onset of the
      stimulus and is sustained for the stimulus duration; 2) transient excitation that
      is correlated with the offset of the stimulus; and 3) transient excitation that
      is correlated with the onset of the stimulus but is delayed in time relative to
      the onset of inhibition. For the neuron to fire, the two excitatory events must
      coincide in time; noncoincident excitatory events are not sufficient.

PMID- 9163364
TI  - Fast and slow activation kinetics of voltage-gated sodium channels in molluscan
      neurons.
AB  - Whole cell patch-clamp recordings of Na current (I(Na)) were made under identical
      experimental conditions from isolated neurons from cephalopod (Loligo, Octopus)
      and gastropod (Aplysia, Pleurobranchaea, Doriopsilla) species to compare
      properties of activation gating. Voltage dependence of peak Na conductance (gNa)
      is very similar in all cases, but activation kinetics in the gastropod neurons
      studied are markedly slower. Kinetic differences are very pronounced only over
      the voltage range spanned by the gNa-voltage relation. At positive and negative
      extremes of voltage, activation and deactivation kinetics of I(Na) are
      practically indistinguishable in all species studied. Voltage-dependent rate
      constants underlying activation of the slow type of Na channel found in
      gastropods thus appear to be much more voltage dependent than are the equivalent
      rates in the universally fast type of channel that predominates in cephalopods.
      Voltage dependence of inactivation kinetics shows a similar pattern and is
      representative of activation kinetics for the two types of Na channels. Neurons
      with fast Na channels can thus make much more rapid adjustments in the number of
      open Na channels at physiologically relevant voltages than would be possible with
      only slow Na channels. This capability appears to be an adaptation that is highly
      evolved in cephalopods, which are well known for their high-speed swimming
      behaviors. Similarities in slow and fast Na channel subtypes in molluscan and
      mammalian neurons are discussed.

PMID- 9163365
TI  - Two-tone distortion on the basilar membrane of the chinchilla cochlea.
AB  - Basilar membrane responses to pairs of tones were measured, with the use of a
      laser velocimeter, in the basal turn of the cochlea in anesthetized chinchillas.
      Frequency spectra of basilar membrane responses to primary tones with frequencies
      (f1, f2) close to the characteristic frequency (CF) contain prominent odd-order
      two-tone distortion products (DPs) at frequencies both higher and lower than CF
      (such as 2f1-f2, 3f1-2f3, 2f2-f1 and 3f2-2f1). For equal-level primaries with
      frequencies such that 2f1-f2 equals CF, the magnitude of the 2f1-f2 DP grows with
      primary level at linear or faster rates at low stimulus levels, but it saturates
      or decreases slightly at higher levels. For a fixed level of one of the primary
      tones, the magnitude of the 2f1-f2 DP is a nonmonotonic function of the level of
      the other primary tone. For low intensities of the variable tone, the 2f1-f2 DP
      grows at a rate of approximately 2 dB/dB with f1 level and 1 dB/dB with f2 level.
      DP magnitudes decrease rapidly with increasing primary frequency ratio (f2/f1) at
      low stimulus levels. For more intense stimuli, DP magnitudes remain constant or
      decrease slowly over a wide range of frequency ratios until a critical value is
      reached, at which DP magnitudes fall with slopes as steep as -300 dB/octave. As
      stimulus level grows, DP phases increasingly lag for large f2/f1 ratios, but
      exhibit leads for small f2/f1 ratios. Cochlear exposure to an intense tone that
      produces large sensitivity losses for the primary frequencies (but only small
      losses for tones with frequency equal to 2f1-f2) causes a substantial decrease in
      magnitude of the 2f1-f2 DP. This result demonstrates that the 2f1-f2 DP
      originates at the basilar membrane region with CFs corresponding to the primary
      frequencies and propagates to the location with CF equal to the DP frequency. 2f1
      f2 DPs on the basilar membrane resemble those measured in human psychophysics in
      most respects. However, the magnitude of basilar membrane DPs does not show the
      nonmonotonic dependence on f2/f1 ratio evident in DP otoacoustic emissions.

PMID- 9163366
TI  - Pharmacological evidence for two types of postsynaptic glycinergic receptors on
      the Mauthner cell of 52-h-old zebrafish larvae.
AB  - The presence of homooligomeric and heterooligomeric glycine receptors (GlyRs) on
      the Mauthner (M) cell in the isolated medulla of 52-h-old zebrafish larvae was
      investigated by analysis of the effects of picrotoxin on glycine-gated channels
      and on glycinergic miniature inhibitory postsynaptic currents (mIPSCs). Two
      functionally different GlyRs have been previously described on the M cell. The
      effects of picrotoxin on these two GlyRs were first analyzed by measuring the
      relative change in their total open probability (NP(o)) with picrotoxin
      concentration. Picrotoxin had no significant effect on the glycine channel with a
      single conductance level of 40-46 pS. In contrast, picrotoxin application
      decreased the NP(o) of the GlyR with multiple subconductance levels. On this
      GlyR, picrotoxin decreased in a concentration-dependent manner the occurrence of
      the 80- to 86-pS substate (median inhibiting concentration = 0.89 microM) and had
      no apparent effect on the 40- to 46-pS opening probability. Opening frequency and
      the mean open times of the 80- to 88-pS main conductance state were reduced in
      the presence of 10 microM picrotoxin, but their relative weight remained
      unchanged. These effects of picrotoxin were not voltage dependent. Picrotoxin
      also modified 40- to 46-pS kinetics. At 100 microM, picrotoxin evoked voltage
      independent flickering during channel openings. Short and long mean open times
      were significantly decreased, whereas the relative proportion of long mean open
      times was increased. The medium closed time was decreased, whereas medium burst
      duration was increased. The burst frequency remained unchanged. Spontaneous
      glycinergic mIPSCs were recorded in the presence of 1 microM tetrodotoxin + 25
      microM bicuculline (holding potential = -50 mV). Application of 10 microM
      picrotoxin did not change the frequency of the synaptic activity, whereas it
      decreased the amplitude of large mIPSCs. No effect was observed on the time to
      peak (0.8 ms) or the mean decay time constant (tau(d) = 7.7 ms). Increasing
      picrotoxin concentration to 100 microM resulted in a decrease of mIPSC frequency
      (35.6%), amplitude (39.8%), and tau(d) (from 7.7 to 5 ms). These results suggest
      that these two functionally different GlyRs correspond to alpha1 homooligomeric
      like and alpha1/beta-heterooligomeric-like GlyRs, and that both are synaptically
      activated. Variation in the proportions of GlyR subtypes from one synapse to
      another could partly account for the broad amplitude distribution of mIPSCs
      recorded from the zebrafish M cell.

PMID- 9163367
TI  - Rapid kinetics and inward rectification of miniature EPSCs in layer I neurons of
      rat neocortex.
AB  - With the use of the whole cell patch-clamp technique combined with visualization
      of neurons in brain slices, we studied the properties of miniature excitatory
      postsynaptic currents (mEPSCs) in rat neocortical layer I neurons. At holding
      potentials (-50 to -70 mV) near the resting membrane potential (RMP), mEPSCs had
      amplitudes of 5-100 pA and were mediated mostly by alpha-amino-3-hydroxy-5-methyl
      4-isoxazoleproprionate (AMPA) receptors. Amplitude histograms were skewed toward
      large events. An N-methyl-D-aspartate (NMDA) component was revealed by
      depolarization to -30 mV or by the use of a Mg2+-free bathing solution. At RMP,
      averaged AMPA mEPSCs had a 10-90% rise time of approximately 0.3 ms (uncorrected
      for instrument filtering). The decay of averaged mEPSCs was best fit by double
      exponential functions in most cases. The fast, dominating component had a decay
      time constant of approximately 1.2 ms and comprised approximately 80% of the
      total amplitude. A small slow component had a decay time constant of
      approximately 4 ms. Positive correlations were found between rise and decay times
      of both individual and averaged mEPSCs, indicative of dendritic filtering. Some
      large-amplitude mEPSCs and spontaneous EPSCs (recorded in the absence of
      tetrodotoxin) had slower kinetics, suggesting a role of asynchronous transmitter
      release in shaping EPSCs. The amplitudes of mEPSCs were much smaller at +60 mV
      than at -60 mV, indicating that synaptic AMPA-receptor-mediated currents were
      inwardly rectifying. These results suggest that neocortical layer I neurons
      receive both NMDA- and AMPA-receptor-mediated synaptic inputs. The rapid decay of
      EPSCs appears to be largely determined by AMPA receptor deactivation. The
      observed rectification of synaptic responses suggests that synaptic AMPA
      receptors in layer I neurons may lack GluR-2 subunits and may be Ca2+ permeable.

PMID- 9163368
TI  - Physiology, pharmacology, and topography of cholinergic neocortical oscillations
      in vitro.
AB  - Rat neocortical brain slices generated rhythmic extracellular field
      [microelectroencephalogram (micro-EEG)] oscillations at theta frequencies (3-12
      Hz) when exposed to pharmacological conditions that mimicked endogenous ascending
      cholinergic and GABAergic inputs. Use of the specific receptor agonist and
      antagonist carbachol and bicuculline revealed that simultaneous muscarinic
      receptor activation and gamma-aminobutyric acid-A (GABA(A))-mediated
      disinhibition were necessary to elicit neocortical oscillations. Rhythmic
      activity was independent of GABA(B) receptor activation, but required intact
      glutamatergic transmission, evidenced by blockade or disruption of oscillations
      by 6-cyano-7-nitroquinoxaline-2,3-dione and (+/-)-2-amino-5-phosphonovaleric
      acid, respectively. Multisite mapping studies showed that oscillations were
      localized to areas 29d and 18b (Oc2MM) and parts of areas 18a and 17. Peak
      oscillation amplitudes occurred in layer 2/3, and phase reversals were observed
      in layers 1 and 5. Current source density analysis revealed large-amplitude
      current sinks and sources in layers 2/3 and 5, respectively. An initial shift in
      peak inward current density from layer 1 to layer 2/3 indicated that two
      processes underlie an initial depolarization followed by oscillatory activity.
      Laminar transections localized oscillation-generating circuitry to superficial
      cortical layers and sharp-spike-generating circuitry to deep cortical layers.
      Whole cell recordings identified three distinct cell types based on response
      properties during rhythmic micro-EEG activity: oscillation-ON (theta-ON) and -OFF
      (theta-OFF) neurons, and transiently depolarizing glial cells. Theta-ON neurons
      displayed membrane potential oscillations that increased in amplitude with
      hyperpolarization (from -30 to -90 mV). This, taken together with a glutamate
      antagonist-induced depression of rhythmic micro-EEG activity, indicated that
      cholinergically driven neocortical oscillations require excitatory synaptic
      transmission. We conclude that under the appropriate pharmacological conditions,
      neocortical brain slices were capable of producing localized theta frequency
      oscillations. Experiments examining oscillation physiology, pharmacology, and
      topography demonstrated that neocortical brain slice oscillations share many
      similarities with the in vivo and in vitro theta EEG activity recorded in other
      brain regions.

PMID- 9163369
TI  - Effects on muscle activity from microstimuli applied to somatosensory and motor
      cortex during voluntary movement in the monkey.
AB  - It is well known that electrical stimulation of primary somatosensory cortex (SI)
      evokes movements that resemble those evoked from primary motor cortex. These
      findings have led to the concept that SI may possess motor capabilities
      paralleling those of motor cortex and speculation that SI could function as a
      robust relay mediating motor responses from central and peripheral inputs. The
      purpose of this study was to rigorously examine the motor output capabilities of
      SI areas with the use of the techniques of spike- and stimulus-triggered
      averaging of electromyographic (EMG) activity in awake monkeys. Unit recordings
      were obtained from primary motor cortex and SI areas 3a, 3b, 1, and 2 in three
      rhesus monkeys. Spike-triggered averaging was used to assess the output linkage
      between individual cells and motoneurons of the recorded muscles. Cells in motor
      cortex producing postspike facilitation (PSpF) in spike-triggered averages of
      rectified EMG activity were designated corticomotoneuronal (CM) cells. Motor
      output efficacy was also assessed by applying stimuli through the microelectrode
      and computing stimulus-triggered averages of rectified EMG activity. One hundred
      seventy-one sites in motor cortex and 68 sites in SI were characterized
      functionally and tested for motor output effects on muscle activity. The
      incidence, character, and magnitude of motor output effects from SI areas were in
      sharp contrast to effects from CM cell sites in primary motor cortex. Of 68 SI
      cells tested with spike-triggered averaging, only one area 3a cell produced
      significant PSpF in spike-triggered averages of EMG activity. In comparison, 20
      of 171 (12%) motor cortex cells tested produced significant postspike effects.
      Single-pulse intracortical microstimulation produced effects at all CM cell sites
      in motor cortex but at only 14% of SI sites. The large fraction of SI effects
      that was inhibitory represented yet another marked difference between CM cell
      sites in motor cortex and SI sites (25% vs 93%). The fact that motor output
      effects from SI were frequently absent or very weak and predominantly inhibitory
      emphasizes the differing motor capabilities of SI compared with primary motor
      cortex.

PMID- 9163370
TI  - Local and propagated dendritic action potentials evoked by glutamate
      iontophoresis on rat neocortical pyramidal neurons.
AB  - Iontophoresis of glutamate at sites on the apical dendrite 278-555 microm from
      the somata of rat neocortical pyramidal neurons evoked low-threshold, small, slow
      spikes and/or large, fast spikes in 71% of recorded cells. The amplitude of the
      small, slow spikes recorded at the soma averaged 9.1 mV, and their apparent
      threshold was <10 mV positive to resting potential. Both their amplitude and
      their apparent threshold decreased as the iontophoretic site was moved farther
      from the soma. These spikes were not abolished by somatic hyperpolarization. When
      the somata of cells displaying these small spikes were voltage clamped at
      membrane potentials that prevented somatic or axonic firing, corresponding
      current spikes could be evoked all-or-none by dendritic depolarization,
      indicating that the small, slow spikes arose in the dendrite. Similar responses
      were not observed during somatic depolarization evoked by current pulses or
      glutamate iontophoresis. These small, slow spikes were abolished by blocking
      voltage-gated Ca2+ channels but not by blocking Na+ channels or N-methyl-D
      aspartate receptors. We conclude that these Ca2+ spikes occurred in a spatially
      restricted region of the dendrite and were not actively propagated to the soma.
      In the presence of 10 mM tetraethylammonium chloride, the amplitudes of the
      iontophoretically evoked Ca2+ spikes were large, similar to those of the Ca2+
      spikes evoked by somatic current injection, but their apparent thresholds were
      63% lower. We conclude that dendritic K+ channels normally prevent the active
      propagation of Ca2+ spikes along the dendrite. In 36% of recorded cells dendritic
      glutamate iontophoresis evoked a Na+ spike with an apparent threshold 63% lower
      than those evoked by somatic current injection or somatic glutamate
      iontophoresis. Blockade of these low-threshold Na+ spikes by pharmacological or
      electrophysiological means often revealed underlying small dendritic Ca2+ spikes.
      When cells displaying the low-threshold Na+ spikes were voltage clamped at
      membrane potentials that prevented firing of the soma or axon, corresponding
      tetrodotoxin-sensitive current spikes could be evoked all-or-none by dendritic
      depolarization. We conclude that these low-threshold Na+ spikes were initiated in
      the dendrite, probably by local Ca2+ spikes, and subsequently propagated actively
      to the soma. Most cells displaying dendritic Na+ spikes fired multiple bursts of
      action potentials during tonic dendritic depolarization, whereas somatic
      depolarization of the same cells evoked only regular firing. We discuss the
      implications of dendritic Ca2+ and Na+ spikes for synaptic integration and neural
      input-output relations.

PMID- 9163371
TI  - Quantitative analysis of firing properties of pyramidal neurons from layer 5 of
      rat sensorimotor cortex.
AB  - Quantitative aspects of repetitive firing evoked by injected current steps and
      ramps were studied in layer 5 pyramidal neurons in brain slices of rat
      sensorimotor cortex to answer the following questions. Do the tonic firing
      properties of burst-firing and regular-spiking (nonbursting) neurons differ
      significantly? Does burst firing denote a discrete class of neurons or represent
      a continuum of firing properties? Is firing rate during the burst of action
      potentials related to stimulus amplitude? What aspect of the stimulus might the
      initial firing rate code? How stable are a neuron's firing properties over time?
      All recorded neurons fired tonically to a long-lasting current above a minimum
      value, and the tonic firing properties of most neurons were quite similar
      irrespective of their initial response to a current step. Only a group of high
      resistance neurons had significantly different tonic firing properties. When slow
      current ramps (rising between 0.5 and approximately 20 nA/s) were applied, the
      relation between firing rate and current during the ramp was very similar to the
      relation between tonic firing rate and current obtained from long-lasting current
      steps. Low-resistance cells exhibited three distinct initial responses to a
      current step: fast adaptation, high-threshold bursts, and low-threshold bursts,
      observed in 54, 28, and 10% of recorded cells, respectively. High-resistance
      cells exhibited a distinctive slow adaptation of firing rate. Slowly adapting,
      fast-adapting (FA), and high-threshold burster (HTB) neurons exhibited no
      adaptation near the minimum current that evoked repetitive firing (I(o)). FA and
      HTB cells exhibited two-spike adaptation to a fina tonic firing rate during
      currents up to 1.6 times I(o). Only a higher current (2.1 times I(o)) evoked a
      burst in HTB cells, whereas a burst was evoked at I(o) in the low-threshold
      burster cells. In most cells analyzed, the initial firing rate, whatever its
      nature, increased monotonically with current step amplitude. The response to fast
      current ramps indicated that firing rate during adaptation or bursting may code
      rate of change of current. Repeated measurements during long-duration impalements
      indicated that both transient and tonic firing properties are stable over time.
      We discuss how the different tonic firing properties of large and small pyramidal
      neurons could be more important functionally than the different transient
      responses (burst/nonburst) of the large neurons. We conclude that the large
      neurons would perform a better linear transduction of time-varying synaptic
      current that reaches their somata. We compare the responses evoked by somatically
      injected current with those evoked by dendritic glutamate iontophoresis in
      previous studies.

PMID- 9163372
TI  - Responses of rat spinal dorsal horn neurons to intracutaneous microinjection of
      histamine, capsaicin, and other irritants.
AB  - To investigate the spinal processing of cutaneous pruritic and algesic stimuli,
      single-unit recordings were made from wide-dynamic-range-type lumbar spinal
      dorsal horn neurons in pentobarbital-sodium-anesthetized rats. Neuronal responses
      were recorded to mechanical and noxious thermal stimuli, as well as to
      microinjection (1 microl) of histamine (0.01-10% = 9 x 10(-1)-9 x 10(-4) M),
      capsaicin (0.1% = 3.3 x 10(-3) M), or other algesic chemicals into skin within
      the receptive field via intracutaneously placed needles. Most (84%) of the 89
      neurons responded to intracutaneous (i.c.) microinjection of histamine with a
      brief phasic discharge followed by an afterdischarge of variable (s to min)
      duration. Ten minutes after i.c. microinjection of histamine (but not NaCl),
      there was a significant increase in the mean area of the low-threshold (but not
      high-threshold) portion of unit mechanical receptive fields. However, responses
      to graded pressure stimuli were not significantly affected after histamine.
      Responses did not exhibit significant tachyphylaxis when histamine
      microinjections were repeated at 5- or 10-min intervals. Unit responses
      significantly increased in a dose-related manner to microinjection of histamine
      at concentrations ranging across 4 orders of magnitude. Within 30 s after i.c.
      microinjection of the H1 antagonist cetirizine, unit responses to i.c. histamine
      delivered at the same skin site were significantly attenuated. Unit responses to
      histamine, as well as to noxious thermal stimulation, were significantly reduced
      after systemic administration of morphine (3.5 mg/kg i.p.) in a naloxone
      reversible manner. Application of a mechanical rub, scratch, or a noxious heat
      stimulus during the unit's ongoing response to i.c. histamine produced a brief
      and marked excitation, often followed by a period of reduced ongoing discharge.
      Unit responses to histamine were markedly suppressed by electrical stimulation in
      the midbrain periaqueductal gray. Most (79%) histamine-responsive units tested
      also responded to i.c. microinjection of capsaicin. After the initial
      microinjection of capsaicin, subsequent responses to histamine and capsaicin
      microinjections were significantly reduced. Units also responded to i.c. ethanol
      (capsaicin vehicle) in a dose-related manner, and showed tachyphylaxis to
      repeated i.c. ethanol at 80% but not at 8%. The mean response to 80% ethanol was
      significantly smaller than to 0.1% capsaicin. All units tested also responded to
      topical application of mustard oil (50%) and i.c. serotonin (30 microg). The
      results are discussed in terms of theories that attempt to reconcile
      psychophysical and clinical observations of pain and itch sensation.

PMID- 9163373
TI  - Serotonin modulates voltage-dependent calcium current in Necturus taste cells.
AB  - Necturus taste buds contain two primary cell types: taste receptor cells and
      basal cells. Merkel-like basal cells are a subset of basal cells that form
      chemical synapses with taste receptor cells and with innervating nerve fibers.
      Although Merkel-like basal cells cannot interact directly with taste stimuli,
      recent studies have shown that Merkel-like basal cells contain serotonin (5-HT),
      which may be released onto taste receptor cells in response to taste stimulation.
      With the use of whole cell voltage clamp, we examined whether focal applications
      of 5-HT to isolated taste receptor cells affected voltage-activated calcium
      current (I(Ca)). Two different effects were observed. 5-HT at 100 microM
      increased I(Ca) in 33% of taste receptor cells, whereas it decreased I(Ca) in
      67%. Both responses used a 5-HT receptor subtype with a pharmacological profile
      similar to that of the 5-HT1A receptor, but the potentiation and inhibition of
      I(Ca) by 5-HT were mediated by two different second-messenger cascades. The
      results indicate that functional subtypes of taste receptor cells, earlier
      defined only by their sensitivity to taste stimuli, may also be defined by their
      response to the neurotransmitter 5-HT and suggest that 5-HT released by Merkel
      like basal cells could modulate taste receptor function.

PMID- 9163374
TI  - Effects of the volatile anesthetic enflurane on spontaneous discharge rate and
      GABA(A)-mediated inhibition of Purkinje cells in rat cerebellar slices.
AB  - The effects of the volatile anesthetic enflurane on the spontaneous action
      potential firing and on gamma-aminobutyric acid-A (GABA(A))-mediated synaptic
      inhibition of Purkinje cells were investigated in sagittal cerebellar slices. The
      anesthetic shifted the discharge patterns from continuous spiking toward burst
      firing and decreased the frequency of extracellularly recorded spontaneous action
      potentials in a concentration-dependent manner. Half-maximal reduction was
      observed at a concentration corresponding to 2 MAC (1 MAC induces general
      anesthesia in 50% of patients and rats). When the GABA(A) antagonist bicuculline
      was present, 2 MAC enflurane reduced action potential firing only by 13 +/- 8%
      (mean +/- SE). In further experiments, inhibitory postsynaptic currents (IPSCs)
      were monitored in the whole cell patch-clamp configuration from cells voltage
      clamped close to -80 mV. At 1 MAC, enflurane attenuated the mean amplitude of
      IPSCs by 54 +/- 3% while simultaneously prolonging the time courses of
      monoexponential current decays by 413 +/- 69%. These effects were similar when
      presynaptic action potentials were suppressed by 1 microM tetrodotoxin. At 1-2
      MAC, enflurane increased GABA(A)-mediated inhibition of Purkinje cells by 97 +/-
      20% to 159 +/- 38%. During current-clamp recordings, the anesthetic (2 MAC)
      hyperpolarized the membrane potential by 5.2 +/- 1.1 mV in the absence, but only
      by 1.6 +/- 1.2 mV in the presence, of bicuculline. These results suggest that
      enflurane-induced membrane hyperpolarizations, as well as the reduction of spike
      rates, were partly caused by an increase in synaptic inhibition. Induction of
      burst firing was related to other actions of the anesthetic, probably an
      accelerated activation of an inwardly directed cationic current and a depression
      of spike afterhyperpolarizations.

PMID- 9163375
TI  - NMDA receptors contribute to primary visceral afferent transmission in the
      nucleus of the solitary tract.
AB  - The nucleus of the solitary tract (NTS) is a principal site for coordinating the
      reflex control of autonomic function. The nucleus receives and organizes primary
      visceral (sensory) afferent inputs from the great vessels, heart, lung, and
      gastrointestinal organs. Glutamate, the excitatory neurotransmitter released by
      the primary afferent fibers, activates non-N-methyl-D-aspartate (non-NMDA)
      receptors on second-order neurons in the NTS. Still in question is whether NMDA
      receptors on the second-order neurons are also activated. Accordingly, the
      purpose of this study was to directly determine whether NMDA receptors contribute
      to synaptic transmission of primary visceral afferent input to second-order
      neurons in the NTS. Whole cell patch-clamp recordings were obtained from
      intermediate and caudal NTS neurons in rat coronal medullary slices. Excitatory
      postsynaptic currents (EPSCs) were evoked by stimulation of the solitary tract (1
      25 V, 0.1 ms, 0.2 or 0.5 Hz) at membrane potentials ranging from -90 to +60 mV.
      In 28 of 32 neurons in which current-voltage relationships were obtained for
      solitary-tract-evoked EPSCs, the currents had short onset latencies (3.42 +/-
      1.03 ms, mean +/- SD), indicating that they were the result of monosynaptic
      activation of second-order neurons. Solitary-tract-evoked EPSCs had both a fast
      and a slow component. The amplitude of the slow component was nonlinearly related
      to voltage (being revealed only at membrane potentials positive to -45 mV),
      blocked by the NMDA receptor antagonist DL-2-amino-5-monophosphovaleric acid
      (APV, 50 microM; n = 12; P = 0.0001), and enhanced in nominally Mg2+-free
      perfusate at membrane potentials negative to -45 mV (n = 5; P = 0.016),
      demonstrating that the slow component was mediated by NMDA receptors. The
      amplitude of the fast component was linearly related to voltage and blocked by
      the non-NMDA receptor antagonist 2,3-dihydroxy-6-nitro-7
      sulfamoylbenzo(F)quinoxaline (NBQX, 3 microM; n = 9; P = 0.0014), demonstrating
      that the fast component was mediated by non-NMDA receptors. The slow component of
      the EPSCs was not blocked by NBQX (n = 6; P = 0.134), nor was the fast component
      blocked by APV (n = 12; P = 0.124). These results show that both NMDA and non
      NMDA receptors coexist on the same second-order NTS neurons and mediate primary
      visceral afferent transmission in the NTS. The participation of NMDA receptors
      suggests that second-order neurons in the NTS may have previously unrecognized
      integrative capabilities in the reflex control of autonomic function.

PMID- 9163376
TI  - Intracellular response properties of units in the dorsal cochlear nucleus of
      unanesthetized decerebrate gerbil.
AB  - Intracellular recording experiments on the dorsal cochlear nuclei of
      unanesthetized decerebrate gerbils were conducted. Acceptable recordings were
      those in which resting potentials were -50 mV or less and action potentials (APs)
      were > or = 40 mV. Responses to short-duration tones and noise, and to current
      pulses delivered via recording electrodes, were acquired. Units were classified
      according to the response map scheme (types I-IV). Ninety-two acceptable
      recordings were made. Most units had simple APs (simple-spiking units); nine
      units had both simple and complex APs, which are bursts of spikes embedded on
      slow, transient depolarizations (complex-spiking units). Of 83 simple-spiking
      units, 46 were classified as follows: type I/III (9 units), type II (9 units),
      type III (25 units), type IV (2 units), and type IV-T (1 unit). One complex
      spiking unit was classifiable (a type III unit); six were unclassifiable because
      of weak acoustic responses. Classifying 39 other simple-spiking units and 2
      complex-spiking units was impossible, because they were either injured or lost
      before sufficient data were acquired. Many simple-spiking units showed
      depolarization or hyperpolarization (approximately 5-10 mV) during acoustic
      stimulation; some were hyperpolarized during the stimulus-off period. Type I/III
      units were not hyperpolarized during off-best-frequency (off-BF) stimulation. In
      contrast, many type II units were hyperpolarized by off-BF frequencies,
      suggesting that they received strong inhibitory sideband inputs. When inhibited,
      some type III units were hyperpolarized. Type IV units were hyperpolarized during
      inhibition even at low levels (<60 dB SPL); sustained depolarizations occurred
      only at higher levels, suggesting that they receive strong inhibitory and weak
      excitatory inputs. Several intracellular response properties were statistically
      different from those of extracellularly recorded units. Intracellularly recorded
      type II units had higher thresholds and lower maximum BF-driven and noise-driven
      rates than their extracellularly recorded counterparts. Type I/III units recorded
      intracellularly had lower maximum BF-driven rates. Type III units recorded
      intracellularly had higher maximum noise rates compared with those recorded
      extracellularly. Weaker acoustic responses most likely result from membrane
      disruption, but heightened responses may be related to weakened chloride-channel
      dependent inhibition due to altered driving forces resulting from KCl leakage.
      Firing rates of simple-spiking units increased monotonically with increasing
      levels of depolarizing current pulses. In contrast, many complex-spiking units
      responded nonmonotonically to depolarizing current injection. The monotonic rate
      versus-current curves and the nonmonotonic rate-versus-sound level curves of type
      IV and III units suggest that the acoustic behavior is the result of extrinsic
      inhibitory inputs and not due solely to intrinsic membrane properties.

PMID- 9163377
TI  - Activation of Ca2+-dependent currents in dorsal root ganglion neurons by
      metabotropic glutamate receptors and cyclic ADP-ribose precursors.
AB  - Cultured dorsal root ganglion neurons were voltage clamped at -90 mV to study the
      effects of intracellular application of nicotinamide adenine dinucleotide
      (betaNAD+), intracellular flash photolysis of caged 3',5'-cyclic guanosine
      monophosphate (cGMP), and metabotropic glutamate receptor activation. The
      activation of metabotropic glutamate receptors evoked inward Ca2+-dependent
      currents in most cells. This was mimicked both by intracellular flash photolysis
      of the caged axial isomer of cGMP [P-1-(2-nitrophenyl)ethyl cGMP] and
      intracellular application of betaNAD+. Whole cell Ca2+-activated inward currents
      were used as a physiological index of raised intracellular Ca2+ levels.
      Extracellular application of 10 microM glutamate evoked the activation of Ca2+
      dependent inward currents, thus reflecting a rise in intracellular Ca2+ levels.
      Similar inward currents were also activated after isolation of metabotropic
      glutamate receptor activation by application of 10 microM glutamate in the
      presence of 20 microM 6-cyano-7-nitroquinoxaline-2,3-dione and 20 microM
      dizocilpine maleate (MK 801), or by extracellular application of 10 microM trans
      (1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid. Intracellular photorelease of
      cGMP, from its caged axial isomer, in the presence of betaNAD+ was also able to
      evoke similar Ca2+-dependent inward currents. Intracellular application of
      betaNAD+ alone produced a concentration-dependent effect on inward current
      activity. Responses to both metabotropic glutamate receptor activation and cGMP
      were suppressed by intracellular ryanodine, chelation of intracellular Ca2+ by
      bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid, and depletion of intracellular
      Ca2+ stores, but were insensitive to the removal of extracellular Ca2+. Therefore
      both cGMP, possibly via a mechanism that involves betaNAD+ and/or cyclic ADP
      ribose, and glutamate can mobilize intracellular Ca2+ from ryanodine-sensitive
      stores in sensory neurons.

PMID- 9163378
TI  - Fast-to-slow conversion following chronic low-frequency activation of medial
      gastrocnemius muscle in cats. I. Muscle and motor unit properties.
AB  - This study of cat medial gastrocnemius (MG) muscle and motor unit (MU) properties
      tests the hypothesis that the normal ranges of MU contractile force, endurance,
      and speed are directly associated with the amount of neuromuscular activity
      normally experienced by each MU. We synchronously activated all MUs in the MG
      muscle with the same activity (20 Hz in a 50% duty cycle) and asked whether
      conversion of whole muscle contractile properties is associated with loss of the
      normal heterogeneity in MU properties. Chronically implanted cuff electrodes on
      the nerve to MG muscle were used for 24-h/day stimulation and for monitoring
      progressive changes in contractile force, endurance, and speed by periodic
      recording of maximal isometric twitch and tetanic contractions under halothane
      anesthesia. Chronic low-frequency stimulation slowed muscle contractions and made
      them weaker, and increased muscle endurance. The most rapid and least variable
      response to stimulation was a decline in force output of the muscle and
      constituent MUs. Fatigue resistance increased more slowly, whereas the increase
      in time to peak force varied most widely between animals and occurred with a
      longer time course than either force or endurance. Changes in contractile force,
      endurance, and speed of the whole MG muscle accurately reflected changes in the
      properties of the constituent MUs both in extent and time course. Normally there
      is a 100-fold range in tetanic force and a 10-fold range in fatigue indexes and
      twitch time to peak force. After chronic stimulation, the range in these
      properties was significantly reduced and, even in MU samples from single animals,
      the range was shown to correspond with the slow (type S) MUs of the normal MG. In
      no case was the range reduced to less than the type S range. The same results
      were obtained when the same chronic stimulation pattern of 20 Hz/50% duty cycle
      was imposed on paralyzed muscles after hemisection and unilateral
      deafferentation. The findings that the properties of MUs still varied within the
      normal range of type S MUs and were still heterogeneous despite a decline in the
      variance in any one property indicate that the neuromuscular activity can account
      only in part for the wide range of muscle properties. It is concluded that the
      normal range of properties within MU types reflects an intrinsic regulation of
      properties in the multinucleated muscle fibers.

PMID- 9163379
TI  - Fast-to-slow conversion following chronic low-frequency activation of medial
      gastrocnemius muscle in cats. II. Motoneuron properties.
AB  - Chronic stimulation (for 2-3 mo) of the medial gastrocnemius (MG) muscle nerve by
      indwelling electrodes renders the normally heterogeneous MG muscle mechanically
      and histochemically slow (type SO). We tested the hypothesis that motoneurons of
      MG muscle thus made type SO by chronic stimulation would also convert to slow
      phenotype. Properties of all single muscle units became homogeneously type SO
      (slowly contracting, nonfatiguing, nonsagging contraction during tetanic
      activation). Motoneuron electrical properties were also modified in the direction
      of type S, fatigue-resistant motor units. Two separate populations were
      identified (on the basis of afterhyperpolarization, rheobase, and input
      resistance) that likely correspond to motoneurons that had been fast (type F) or
      type S before stimulation. Type F motoneurons, although modified by chronic
      stimulation, were not converted to the type S phenotype, despite apparent
      complete conversion of their muscle units to the slow oxidative type (type SO).
      Muscle units of the former type F motor units were faster and/or more powerful
      than those of the former type S motor units, indicating some intrinsic regulation
      of motor unit properties. Experiments in which chronic stimulation was applied to
      the MG nerve cross-regenerated into skin yielded changes in motoneuron properties
      similar to those above, suggesting that muscle was not essential for the effects
      observed. Modulation of group Ia excitatory postsynaptic potential (EPSP)
      amplitude during high-frequency trains, which in normal MG motoneurons can be
      either positive or negative, was negative in 48 of 49 chronically stimulated
      motoneurons. Negative modulation is characteristic of EPSPs in motoneurons of
      most fatigue-resistant motor units. The general hypothesis of a periphery-to
      motoneuron retrograde mechanism was supported, although the degree of control
      exerted by the periphery may vary: natural type SO muscle appears especially
      competent to modify motoneuron properties. We speculate that activity-dependent
      regulation of the neurotrophin-(NT) 4/5 in muscle plays an important role in
      controlling muscle and motoneuron properties.

PMID- 9163380
TI  - Auditory cortical onset responses revisited. I. First-spike timing.
AB  - Sound onsets are salient and behaviorally relevant, and most auditory neurons
      discharge spikes locked to such transients. The acoustic parameters of sound
      onsets that shape such onset responses are unknown. In this paper is analyzed the
      timing of spikes of single neurons in the primary auditory cortex of barbiturate
      anesthetized cats to the onsets of tone bursts. By parametric variation of sound
      pressure level, rise time, and rise function (linear or cosine-squared), the time
      courses of peak pressure, rate of change of peak pressure, and acceleration of
      peak pressure during the tones' onsets were systematically varied. For cosine
      squared rise function tones of a given frequency and laterality, any neuron's
      mean first-spike latency was an invariant and inverse function of the maximum
      acceleration of peak pressure occurring at tone onset. For linear rise function
      tones, latency was an invariant and inverse function of the rate of change of
      peak pressure. Thus latency is independent of rise time or sound pressure level
      per se. Latency-acceleration functions, obtained with cosine-squared rise
      function tones under different stimulus conditions (frequency, laterality) from
      any given neuron and across the neuronal pool, were of strikingly similar shape.
      The same was true for latency-rate of change of peak pressure functions obtained
      with linear rise function tones. Latency-acceleration/rate of change of peak
      pressure functions could differ in their extent and in their position within the
      coordinate system. The positional differences reflect neuronal differences in
      minimum latency Lmin and in a sensitivity S to acceleration and rate of change of
      peak pressure (transient sensitivity), a hitherto unrecognized neuronal property
      that is distinctly different from firing threshold. Estimates of Lmin and S,
      which were derived by fitting a simple function to the neuronal latency
      acceleration/rate of change of peak pressure functions, were independent of rise
      function. On average, Lmin decreased with increasing characteristic frequency
      (CF), but varied widely for neurons with the same CF. S varied with CF in a
      fashion similar to the cat's audiogram and, for a given neuron, varied with
      frequency. SD of first-spike latency was roughly proportional to the slope of the
      functions relating latency to acceleration/rate of change of peak pressure. Thus
      SD increased exponentially, rather than linearly, with mean latency, and did so
      at about twice the rate for linear than for cosine-squared rise function tones.
      The proportionality coefficients were quite similar across the neuronal pool and
      similar for both rise functions. Minimum SD increased nonlinearly with increasing
      Lmin. These findings suggest a peripheral origin of S and a peripheral
      establishment of latency-acceleration/rate of change of peak pressure functions.
      Because of the striking similarity in the shapes of such functions across the
      neuronal pool, sound onsets will produce orderly and predictable spatiotemporal
      patterns of first-spike timing, which could be used to instantaneously track
      rapid transients and to represent transient features by partly scale-invariant
      temporal codes.

PMID- 9163381
TI  - Auditory cortical onset responses revisited. II. Response strength.
AB  - Most neurons of the auditory pathway discharge spikes locked to the onset of an
      acoustic stimulus, but it is largely unknown in which way the acoustic parameters
      of sound onsets shape the neuronal responses. In this paper is analyzed the
      number of spikes discharged by single neurons in primary auditory cortex of
      barbiturate-anesthetized cats to the onsets of tones of characteristic frequency.
      The time course of the peak pressure (i.e., the envelope) was altered by
      parametrically varying sound pressure level (SPL), rise time, and rise function
      (linear or cosine-squared). For both rise functions, rise time had manifold, and
      in some cases dramatic, effects on conventional spike count-level functions. In
      general, threshold SPL, dynamic range, and the lowest SPL at which monotonic
      spike count functions saturated increased with prolongation of the rise time. In
      neurons with mostly nonmonotonic spike count-level functions, "best SPL"
      increased and the descending high-SPL arms flattened, so that functions obtained
      with long rise times were often monotonic whereas those obtained with shorter
      rise times were highly nonmonotonic. Consequently, the "tuning" to SPL was less
      sharp for longer rise time tones, and spike count versus rise time functions
      changed from "short-pass" to "long-pass" with an increase in SPL. Systematic
      effects of rise time persisted when spike counts were plotted against the rate of
      change of peak pressure or against the maximum acceleration of peak pressure.
      However, when spike counts were plotted as a function of the instantaneous peak
      pressure at the time of response initiation, the functions obtained with
      different rise times, and even with different rise functions, were in close
      register. This suggests that the stimulus-dependent component of first-spike
      latency can be viewed as an integration window, during which rate of change of
      peak pressure is integrated. The window commences with tone onset and its
      duration is inversely related to the maximum acceleration (or, for linear rise
      functions, the rate of change) of peak pressure and the neuron's transient
      sensitivity. The present findings seriously question, for onset responses, the
      usefulness of the spike count-level function and measures derived from it, such
      as threshold SPL, dynamic range, best SPL, or degree of nonmonotonicity. They
      further cast doubt onto the validity of current concepts of intensity coding at
      cortical levels, because most neurons' onset responses are not indicative of a
      signal's steady-state SPL. However, they suggest a mechanism by which a neuronal
      population will sample a given transient in an orderly, sensitivity-dependent,
      temporal sequence. The sampling rate is automatically adjusted to, and adjusted
      by, the rapidity of the signal's change. And the instantaneous properties of the
      transient could be represented by the ratios and spatial distribution of
      responses across the simultaneously active subpopulation. Such a mechanism could
      provide the basis for the demonstrated capability of discrimination of rapid
      transients.

PMID- 9163382
TI  - Physiology and pharmacology of corticothalamic stimulation-evoked responses in
      rat somatosensory thalamic neurons in vitro.
AB  - Whole cell current- and voltage-clamp recording techniques were employed in a rat
      thalamocortical slice preparation to characterize corticothalamic stimulation
      evoked responses in thalamic neurons. Three types of corticothalamic stimulation
      evoked responses were observed in thalamic neurons. Of thalamic neurons, 57%
      responded to corticothalamic stimulation with purely excitatory synaptic
      responses, whereas 27% had inhibitory synaptic responses and 16% had mixed
      excitatory/inhibitory responses. This suggested corticothalamic activation of
      multiple distinct synaptic circuits, presumably involving both nucleus
      reticularis thalami (NRT) and thalamus, because the rat ventrobasal complex is
      virtually devoid of GABAergic interneurons. Corticothalamic-stimulation-evoked
      excitatory postsynaptic currents (EPSCs) were predominantly slow rising currents
      that showed nonlinear voltage dependence, characteristics of an N-methyl-D
      aspartate (NMDA)-receptor-mediated synaptic current. These slow rising EPSCs were
      blocked by the NMDA antagonist 2-amino-5-phosphonovaleric acid (APV). A minority
      of corticothalamic EPSCs had faster kinetics, and were blocked by 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX). Corticothalamic stimulation of varying
      frequency optimally activated burst responses in thalamic neurons at low
      frequencies (3-6 Hz). The optimal 3- to 6-Hz response was reduced by
      ethosuximide, by APV, and by detaching the neocortex from the thalamocortical
      slice, suggesting that T current, NMDA receptors, and neocortical properties all
      contributed to generation of this 3- to 6-Hz frequency preference. In contrast to
      corticothalamic EPSCs, medial-thalamic-stimulation-evoked responses consisted of
      fast CNQX-sensitive EPSCs that were predominantly voltage insensitive, with no 3-
      to 6-Hz frequency preference. In thalamic neurons in which corticothalamic
      stimulation evoked predominantly inhibitory synaptic responses, this inhibitory
      postsynaptic potential (IPSP) had early and late phases, often followed by a
      rebound burst. The early IPSP reversed at -95 mV and was bicuculline sensitive,
      whereas the late IPSP reversed at -113 mV and was blocked by the gamma
      aminobutyric acid-B (GABA(B)) antagonist 3-N[1-(S)-(3,4
      dichlorophenyl)ethyl]amino-2-(S)-hydroxypropyl-P-benzy lphoshinic acid (CGP
      55845A). In thalamic neurons in which corticothalamic stimulation evoked a mixed
      excitatory postsynaptic potential (EPSP)/IPSP response, repetitive
      corticothalamic stimulation rapidly reduced IPSPs and enhanced EPSPs at higher
      frequencies. This resulted in burst firing being triggered in these mixed
      response neurons at frequencies >6 Hz. Corticothalamic feedback onto thalamic
      relay neurons activated diverse responses due to differing relative activation of
      NRT and "feedforward" inhibitory responses. These multiple in vitro
      corticothalamic responses differ from responses encountered in other in vitro
      thalamic preparations lacking a synaptically connected neocortex, but are similar
      to results evident in thalamic neurons in response to cortical stimulation in
      vivo. In addition, the thalamocortical 3- to 6-Hz frequency preference was
      conserved, suggesting that many factors critical for this emergent property of
      the thalamocortical system are maintained in vitro.

PMID- 9163383
TI  - Spatial and temporal integration of signals in foveal line orientation.
AB  - The discrimination of the orientation of a line improves with line length,
      reaching an optimum when a foveal line is approximately 0.5 degrees long. We
      studied the effect of eliminating sections of the line, of displacing them out of
      alignment, and of delaying them. Orientation discrimination thresholds are only a
      little elevated when a 25-arcmin line is replaced by three equally spaced
      collinear 5-arcmin segments. Two collinear 5-arcmin segments show better
      thresholds than a single one when they are separated by as much as 20 arcmin. But
      thresholds are impaired by bringing line segments out of collinearity by as
      little as 1 arcmin. Asynchrony of up to 50 ms can be tolerated, but when the
      middle segment of a three-line pattern is delayed by approximately 100 ms there
      is active inhibition, thresholds being now higher than when the middle segment is
      absent. It is concluded that for signals to address the orientation
      discrimination mechanism optimally, they have to be contained inside a narrow
      spatial corridor and be presented within a time window of approximatley 50 ms,
      but that some spatial summation can take place over a length of > or = 0.5
      degrees in the fovea. Because short lines made of black and white collinear
      segments do not have good orientation thresholds, whereas longer and interrupted
      lines do, it is concluded that what is involved is potentiating interaction
      between collinearly arranged neurons with identical orientation selectivity
      rather than summation of signals within the receptive fields of single neurons.

PMID- 9163384
TI  - Network properties of the dentate gyrus in epileptic rats with hilar neuron loss
      and granule cell axon reorganization.
AB  - Neuron loss in the hilus of the dentate gyrus and granule cell axon
      reorganization have been proposed as etiologic factors in human temporal lobe
      epilepsy. To explore these possible epileptogenic mechanisms,
      electrophysiological and anatomic methods were used to examine the dentate gyrus
      network in adult rats that had been treated systemically with kainic acid. All
      kainate-treated rats, but no age-matched vehicle-treated controls, were observed
      to have spontaneous recurrent motor seizures beginning weeks to months after
      exposure to kainate. Epileptic kainate-treated rats and control animals were
      anesthetized for field potential recording from the dentate gyrus in vivo.
      Epileptic kainate-treated rats displayed spontaneous positivities ("dentate
      electroencephalographic spikes") with larger amplitude and higher frequency than
      those in control animals. After electrophysiological recording, rats were
      perfused and their hippocampi were processed for Nissl and Timm staining.
      Epileptic kainate-treated rats displayed significant hilar neuron loss and
      granule cell axon reorganization. It has been hypothesized that hilar neuron loss
      reduces lateral inhibition in the dentate gyrus, thereby decreasing seizure
      threshold. To assess lateral inhibition, simultaneous recordings were obtained
      from the dentate gyrus in different hippocampal lamellae, separated by 1 mm. The
      perforant path was stimulated with paired-pulse paradigms, and population spike
      amplitudes were measured. Responses were obtained from one lamella while a
      recording electrode in a distant lamella leaked saline or the gamma-aminobutyric
      acid-A receptor antagonist bicuculline. Epileptic kainate-treated and control
      rats both showed significantly more paired-pulse inhibition when a lateral
      lamella was hyperexcitable. To assess seizure threshold in the dentate gyrus, two
      techniques were used. Measurement of stimulus threshold for evoking maximal
      dentate activation revealed significantly higher thresholds in epileptic kainate
      treated rats compared with controls. In contrast, epileptic kainate-treated rats
      were more likely than controls to discharge spontaneous bursts of population
      spikes and to display stimulus-triggered afterdischarges when a focal region of
      the dentate gyrus was disinhibited with bicuculline. These spontaneous bursts and
      afterdischarges were confined to the disinhibited region and did not spread to
      other septotemporal levels of the dentate gyrus. Epileptic kainate-treated rats
      that displayed spontaneous bursts and/or afterdischarges had significantly larger
      percentages of Timm staining in the granule cell and molecular layers than
      epileptic kainate-treated rats that failed to show spontaneous bursts or
      afterdischarges. In summary, this study reveals functional abnormalities in the
      dentate gyri of epileptic kainate-treated rats; however, lateral inhibition
      persists, suggesting that vulnerable hilar neurons are not necessary for
      generating lateral inhibition in the dentate gyrus.

PMID- 9163385
TI  - Order of application determines the interaction between phorbol esters and GTP
      gamma-S in dorsal raphe neurons: evidence that the effect of 5-HT is modified
      upstream of the G protein Ca channel interaction.
AB  - Phorbol esters activating protein kinase C (PKC) partially uncouple the
      inhibitory effect of serotonin (5-HT) from serotonergic neuron Ca2+ current.
      Presently the site of action of PKC is not known and may be the receptor, G
      protein, or ion channel. We recorded Ca2+ current from acutely isolated neurons
      with the use of the patch-clamp technique to study the site of action of PKC.
      Activation of the G protein with internal guanosine 5'-O-(3-thiotriphosphate)
      (GTP-gamma-S) occluded the response to 5-HT, but unexpectedly this effect was not
      reversed by the addition of the phorbol ester phorbol 12-myristate 13-acetate
      (PMA) despite the voltage-dependent reversal of the effect of GTP-gamma-S by long
      depolarizing steps to +80 mV. PMA was, however, able to partially reverse 5-HT
      induced inhibition of Ca2+ current. The rate of reinhibition of the Ca2+ current
      (related to the concentration of activated G proteins) by GTP-gamma-S after the
      addition of PMA at -50 mV was identical to the rate when only GTP-gamma-S was
      present. By contrast, when cells were exposed first to PMA, and then GTP-gamma-S
      was perfused into the cell, GTP-gamma-S lost about half of its ability to
      activate the G protein. The rate of reinhibition of the Ca2+ current by internal
      GTP-gamma-S was also reduced in cells pretreated with PMA. The original result in
      which PMA did not reverse the action of GTP-gamma-S suggested that the channel
      was not the functional site of action of PMA, nor was the site on the G protein
      that binds to the channel, but it did not rule out the receptor. When the
      receptor was bypassed, after prior PKC activation, it was found that direct
      activation of the G protein by a nonhydrolyzable analogue of GTP was reduced;
      taken as a whole, this indicates that in dorsal raphe, and perhaps other neurons,
      the site of the critical phosphorylation may be on the G protein and possibly at
      the GTP binding site.

PMID- 9163387
TI  - Effects of anions on ATP-activated nonselective cation current in NG108-15 cells.
AB  - Extracellular ATP induces a nonselective cation current and elevates
      intracellular Ca2+ concentration via P2Z receptors in NG108-15 cells. We found
      that the ATP-induced nonselective cation current became larger in methanesulfonic
      acid (MS-) than in Cl- external solution. We therefore examined the effects of
      various external anions on the ATP-induced cation current with the use of the
      whole cell patch-clamp technique. The concentration-response curves for ATP were
      obtained in different anionic external solutions. The maximum current density
      (Imax) and the concentration of agonist that gives 50% of maximum response (EC50)
      value of ATP were obtained by fitting the curves with the use of the Hill
      coefficient of 2. The apparent Imax decreased in the order of aspartic acid (Asp
      ) > MS- > F- > Cl- > Br- > or = I-. The apparent EC50 values for ATP were shifted
      to the right in the sequence of Asp- < F- < MS- < Br- < Cl- < I-. Thus both Imax
      and EC50 values were affected by anions, indicating that anions are mixed-type
      inhibitors of the ATP-induced current. The shift of the EC50 values of ATP
      indicates that anions interfere with ATP binding to the receptor. External Cl-
      was a noncompetitive inhibitor with respect to external Na+, a major cation
      carrying the ATP-induced current. We conclude that extracellular anions inhibit
      the ATP-induced nonselective cation current at least partly by interfering with
      ATP binding to the P2Z receptor, which is associated with the nonselective cation
      channels.

PMID- 9163386
TI  - Development of chewing in children from 12 to 48 months: longitudinal study of
      EMG patterns.
AB  - Developmental changes in the coordinative organization of masticatory muscles
      were examined longitudinally in four children over 49 experimental sessions
      spanning the age range of 12-48 mo. Electromyographic (EMG) records were obtained
      for right and left masseter muscles, right and left temporalis muscles, and the
      anterior belly of the digastric. Two independent analytic processes were
      employed, one that relied on identification of onset and offset of muscle
      activation and a second that used pairwise cross-correlational techniques. The
      results of these two analyses, which were found to be consistent with each other,
      demonstrated that the basic chewing pattern of reciprocally activated
      antagonistic muscle groups is established by 12 mo of age. Nevertheless, chewing
      efficiency appears to be improved through a variety of changes in the chewing
      pattern throughout early development. Coupling of activity among the jaw elevator
      muscles was shown to strengthen with maturation, and the synchrony of onset and
      offset of these muscles also increased. Coactivation of antagonistic muscles
      decreased significantly with development. This decrease in antagonistic
      coactivation and increase in synchrony among jaw elevators, and a parallel
      decrease in EMG burst duration, were taken as evidence of increased chewing
      efficiency. No significant differences in the frequency of chewing were found
      across the ages studied. Additional considerations include the appropriateness of
      this coordinative infrastructure for other developing oromotor skills, such as
      speech production. It is suggested that the relatively fixed coordinative
      framework for chewing exhibited by these children would not be suitable for
      adaptation to speech movements, which have been shown to rely on a much more
      variable and adjustable coordinative organization.

PMID- 9163388
TI  - Blockade of GABAergic inhibition reveals reordered cortical somatotopic maps in
      rats that sustained neonatal forelimb removal.
AB  - A previous study from this laboratory demonstrated that forelimb removal at birth
      results in invasion of the cuneate nucleus (CN) by sciatic nerve axons and the
      development of CN cells including thalamic projection neurons with receptive
      fields that include both the forelimb stump and the hindlimb. However, recordings
      from unit clusters in lamina IV of the primary somatosensory cortex (SI) of these
      animals revealed the presence of only a very few sites in the forelimb stump
      representation where responses to hindlimb stimulation could also be recorded. In
      the present study we tested the possibility that input from the hindlimb was
      suppressed in lamina IV of the cortical stump representation via GABAergic
      inhibitory mechanisms by mapping this cortical region, applying the gamma
      aminobutyric acid-A (GABA(A)) and GABA(B) receptor antagonists bicuculline and
      phaclofen (50 microM each), and then remapping the same sites. In six neonatally
      manipulated rats, 15 of 242 sites (6.2%) in the stump representation responded to
      hindlimb stimulation before GABA receptor blockade and 107 (44.2%) of the same
      sites responded to stimulation of the hindlimb during blockade (P < 0.05). In six
      normal adult rats, 7 of 264 sites (2.7%) in the forelimb representation responded
      to hindlimb stimulation before the application of bicuculline and phaclofen.
      During GABA receptor blockage, 31 of these sites (11.7%) responded to such
      stimulation (P < 0.02 vs. the untreated normal cortex and P < 0.01 vs. the
      neonatally manipulated rats treated with GABA blockers). To specifically test the
      role of GABA(A) versus GABA(B) receptors in the inhibition of hindlimb input to
      the SI stump representation in rats that sustained neonatal forelimb removal,
      either bicuculline or phaclofen alone was applied to SI in nine neonatally
      manipulated animals. In four rats treated with bicuculline, 12 of 184 sites
      (6.5%) in the stump representation responded to hindlimb stimulation before
      treatment and 61 of 184 sites (33.2%) responded to such stimulation during
      application (P < 0.01). In animals (n = 5) treated with phaclofen, 18 of 251
      sites (7.2%) responded to hindlimb stimulation before treatment and 64 of these
      sites (25.5%) responded to such stimulation during application (P < 0.05). There
      was no significant difference between the results obtained with bicuculline
      alone, phaclofen alone, or the two GABA blockers delivered together (P > 0.05).
      These results indicate that hindlimb input to the portion of SI representing the
      forelimb stump is functionally suppressed in rats that have sustained neonatal
      forelimb removal and that GABAergic inhibition, mediated by both GABA(A) and
      GABA(B) receptors, is involved in this process.

PMID- 9163389
TI  - Low-amplitude oscillations in the inferior olive: a model based on electrical
      coupling of neurons with heterogeneous channel densities.
AB  - The mechanism underlying subthreshold oscillations in inferior olivary cells is
      not known. To study this question, we developed a single-compartment, two
      variable, Hodgkin-Huxley-like model for inferior olive neurons. The model
      consists of a leakage current and a low-threshold calcium current, whose kinetics
      were experimentally measured in slices. Depending on the maximal calcium and leak
      conductances, we found that a neuron model's response to current injection could
      be of four qualitatively different types: always stable, spontaneously
      oscillating, oscillating with injection of current, and bistable with injection
      of current. By the use of phase plane techniques, numerical integration, and
      bifurcation analysis, we subdivided the two-parameter space of channel densities
      into four regions corresponding to these behavioral types. We further developed,
      with the use of such techniques, an empirical rule of thumb that characterizes
      whether two cells when coupled electrically can generate sustained, synchronized
      oscillations like those observed in inferior olivary cells in slices, of low
      amplitude (0.1-10 mV) in the frequency range 4-10 Hz. We found that it is not
      necessary for either cell to be a spontaneous oscillator to obtain a sustained
      oscillation. On the other hand, two spontaneous oscillators always form an
      oscillating network when electrically coupled with any arbitrary coupling
      conductance. In the case of an oscillating pair of electrically coupled
      nonidentical cells, the coupling current varies periodically and is nonzero even
      for very large coupling values. The coupling current acts as an equalizing
      current to reconcile the differences between the two cells' ionic currents. It
      transiently depolarizes one cell and/or hyperpolarizes the other cell to obtain
      the regenerative response(s) required for the synchronized oscillation. We
      suggest that the subthreshold oscillations observed in the inferior olive can
      emerge from the electrical coupling between neurons with different channel
      densities, even if the inferior olive nucleus contains no or just a small
      proportion of spontaneously oscillating neurons.

PMID- 9163390
TI  - Abnormal access of axial vibrotactile input to deafferented somatosensory cortex
      in human upper limb amputees.
AB  - We studied two human subjects with total deafferentation of one upper limb
      secondary to traumatic multiple cervical root avulsions. Both subjects developed
      a phantom limb and underwent elective amputation of the paralyzed, deafferentated
      limb. Psychophysical study revealed in each subject an area of skin in the
      pectoral region ipsilateral to the amputation where vibrotactile stimulation (VS)
      elicited referred sensations (RS) in the phantom limb. Positron emission
      tomography was then used to measure regional cerebral blood flow changes during
      VS of the pectoral region ipsilateral to the amputation with RS and during VS of
      a homologous part of the pectoral region adjacent to the intact arm without RS. A
      voxel-based correlation analysis was subsequently used to study functional
      connectivity. VS of the pectoral region adjacent to the intact arm was associated
      with activation of the dorsal part of the contralateral primary somatosensory
      cortex (S1) in a position consistent with the S1 trunk area. In contrast, VS of
      the pectoral region ipsilateral to the amputation with RS was associated with
      activation of the contralateral S1 that extended from the level of the trunk
      representation ventrally over distances of 20 and 12 mm, respectively, in the two
      subjects. The area of S1 activated during VS of the digits in a normal control
      subject was coextensive with the ventral S1 region abnormally activated during VS
      of the ectopic phantom representation in the two amputees, suggesting that the
      deafferented digit or hand/arm area had been activated by sensory input from the
      pectoral region. Correlation analysis showed an abnormal pattern of intrinsic
      connectivity within the deafferented S1 hand/arm area of both amputees. In one
      subject, the deafferented S1 was functionally connected with 3 times as many S1
      voxels as the normally afferented S1. This abnormal functional connectivity
      extended in both the rostrocaudal and ventrodorsal dimensions. The results
      demonstrate that sensory input delivered to the axial body surface may gain
      access to the S1 hand/arm area in some humans who have suffered extensive
      deafferentation of this area. The findings are consistent with the hypothesis
      that deafferentation of an area of S1 may result in activation of previously
      dormant inputs from body surfaces represented in immediately adjacent parts of
      S1. The results also provide evidence that changes in functional connectivity
      between these adjacent areas of the cortex play a role in the somatotopic
      reorganization.

PMID- 9163392
TI  - Ocular dominance in human V1 demonstrated by functional magnetic resonance
      imaging.
AB  - Very high resolution functional magnetic resonance imaging (fMRI) at a 4 Tesla
      (T) magnetic field was used to map ocular dominance regions in the human visual
      cortical layers using the blood oxygen level dependent (BOLD) contrast mechanism.
      The fMRI response from primary visual cortex (V1) exhibited a distribution of
      ocular dominance reminiscent of the single-cell recordings of Hubel and Wiesel.
      Pixels could be grouped into seven categories varying from left-only response to
      binocular-only response to right-only responses. Nonspecific responses were found
      in the MRI-visible draining veins as well as in the parenchyma. Although large
      vessel BOLD signals are easily detectable, regardless of field strength, they
      demonstrate a fMRI response to photic input that could not be used to distinguish
      ocular dominance. The difference in BOLD response between a region activated by
      one eye and that activated by the other is only 2.9% on average. This
      necessitates the use of a difference paradigm to visualize the regions of ocular
      dominance accurately. The data show that BOLD-based fMRI is sensitive to neuronal
      activity in cortical columns when using differential techniques, opening up the
      possibility of mapping specialized populations of neurons in humans that are not
      accessible to electrophysiological or other methods of invasive mapping.

PMID- 9163391
TI  - Excitatory and inhibitory vestibular pathways to the extraocular motor nuclei in
      goldfish.
AB  - Electrophysiological, ultrastructural, and immunohistochemical techniques were
      utilized to describe the excitatory and inhibitory vestibular innervation of
      extraocular motor nuclei in the goldfish. In antidromically activated oculomotor
      motoneurons, electrical stimulation of the intact contralateral vestibular nerve
      produced short-latency, variable amplitude electrotonic excitatory postsynaptic
      potentials (EPSPs) at 0.5-0.7 ms followed by chemical EPSPs at 1.0-1.3 ms.
      Stimulation of the ipsilateral vestibular nerve produced small amplitude membrane
      hyperpolarizations at a latency of 1.3-1.7 ms in which equilibrium potentials
      were slightly more negative than resting potentials. The inhibitory postsynaptic
      potentials (IPSPs) reversed with large amplitudes after the injection of chloride
      ions suggesting a proximal soma-dendritic location of terminals exhibiting high
      efficacy inhibitory synaptic conductances. In antidromically identified abducens
      motoneurons and putative internuclear neurons, electrical stimulation of the
      contralateral vestibular nerve produced large-amplitude, short-latency
      electrotonic EPSPs at 0.5 ms followed by chemical depolarizations at 1.2-1.3 ms.
      Stimulation of the ipsilateral vestibular nerve evoked IPSPs at 1.4 ms that were
      reversed after injection of current and/or chloride ions. gamma-Aminobutyric acid
      (GABA) antibodies labeled inhibitory neurons in vestibular subdivisions with
      axons projecting into the ipsilateral medial longitudinal fasciculus (MLF).
      Putative GABAergic terminals surrounded oculomotor, but not abducens, motoneurons
      retrogradely labeled with horseradish peroxidase. Hence the spatial distribution
      of GABAergic neurons and terminals appears highly similar in the vestibuloocular
      system of goldfish and mammals. Electron microscopy of motoneurons in the
      oculomotor and abducens nucleus showed axosomatic and axodendritic synaptic
      endings containing spheroidal synaptic vesicles establishing chemical, presumed
      excitatory, synaptic contacts with asymmetric pre- and/or postsynaptic membrane
      specializations. The majority of contacts with spheroidal vesicles displayed gap
      junctions in which the chemical and electrotonic synapses were either en face to
      dissimilar or adjacent to one another on the same soma/dendritic profiles.
      Another separate set of axosomatic synaptic endings, presumed to be inhibitory,
      contained pleiomorphic synaptic vesicles with symmetric pre- and/or postsynaptic
      membrane specializations that never included gap junctions. Excitatory and
      inhibitory synaptic contacts appeared equal in number but were more sparsely
      distributed along the soma-dendritic profiles of oculomotor as compared with
      abducens motoneurons. Collectively these data provide evidence for both
      disynaptic vestibular inhibition and excitation in all subdivisions of the
      extraocular motor nuclei suggesting the basic vestibulooculomotor blueprint to be
      conserved among vertebrates. We propose that unique vestibular neurons,
      transmitters, pathways, and synaptic arborizations are homologous structural
      traits that have been essentially preserved throughout vertebrate phylogeny by a
      shared developmental plan.

PMID- 9163393
TI  - Lateral and medial olivocochlear neurons have distinct electrophysiological
      properties in the rat brain slice.
AB  - Electrical properties of cochlear efferent (olivocochlear) neurons were
      investigated with the use of the whole cell patch recording technique in slice
      preparations of the neonatal rat (postnatal days 5-11). Lateral and medial
      olivocochlear (LOC and MOC, respectively) neurons were retrogradely labeled with
      a fluorescent tracer injected into the cochlea. Stained neurons were identified
      under a fluorescence microscope, and they were subjected to whole cell recording.
      LOC and MOC neurons showed different electrophysiological properties. Both showed
      spike trains of tonic pattern in response to injection of depolarizing current
      pulses at the resting membrane potential (-60 to -70 mV). However, when the
      membrane was slightly hyperpolarized (-72 to -76 mV), LOC neurons showed spike
      trains with a long first interspike interval (ISI), whereas MOC neurons showed
      spike trains with a long latency to the first spike. Extracellular application of
      4-aminopyridine (4-AP; 0.5-2 mM) shortened these ISIs and latencies. In voltage
      clamp experiments, two transient outward currents with different (fast and slow)
      decay kinetics were observed in LOC neurons. The fast outward current (I(A-LOC))
      was inactivated by the preceding depolarization, and decayed with a time constant
      (tau) of 86 ms (at 0 mV). The preceding potential, which reduced the current size
      to the half-maximum (V1/2), was -72 mV. The slow current (I(KD)) decayed with a
      tau of 853 ms (at 0 mV). I(A-LOC) was sensitive to 4-AP (2 mM), and was less
      sensitive to tetraethylammonium chloride (TEA; 20 mM). I(KD) was partially
      blocked by TEA (20 mM), but was insensitive to 4-AP (2 mM). The recovery from
      inactivation of I(A-LOC) was time dependent with a time constant (tau(rec)) of 32
      ms at -90 mV. MOC neurons also showed a transient outward current that consisted
      of a single transient component (I(A-MOC)) with a steady outward current. I(A
      MOC) was inactivated by the preceding depolarization. Decay tau of I(A-MOC) was
      33 ms (at 0 mV), and V1/2 was -75 mV. I(A-MOC) was sensitive to 4-AP (0.5-1 mM).
      The time-dependent recovery from inactivation of I(A-MOC) was faster than that of
      I(A-LOC), and tau(rec) was 15 ms at -90 mV. The different kinetics of transient
      outward currents between LOC and MOC neurons seems to be responsible for the
      difference in firing properties of these two neurons.

PMID- 9163394
TI  - Presynaptically silent synapses: spontaneously active terminals without stimulus
      evoked release demonstrated in cortical autapses.
AB  - This study addresses the question of whether synapses that are capable of
      releasing transmitters spontaneously can also release them in an excitation
      dependent manner. For this purpose, whole cell patch recordings were performed
      for a total of 48 excitatory solitary neurons in a microisland culture to observe
      excitatory autaptic currents elicited by spontaneous transmitter release as well
      as by somatic excitation. A somatic Na+-spike, induced in response to a short
      voltage step, evoked excitatory postsynaptic currents (EPSCs) of various
      amplitudes through the autapses; in some cases, no response was noticeable. To
      make sure that the recorded autaptic spontaneous EPSCs (sEPSCs) under a voltage
      clamp resulted from independent release of transmitters and were not associated
      with action potentials, sEPSCS in the presence and absence of tetrodotoxin (TTX)
      were compared in six cells. In the presence of TTX the evoked EPSCs were
      completely eliminated, whereas the sEPSCs were still observed and the amplitude
      distribution histograms were statistically not different from those recorded in
      the absence of TTX. A quantitative analysis of the sEPSCs (presumably miniature
      EPSCs) showed that the amplitude of stimulus-evoked EPSCs did not correlate with
      either the frequency or median amplitudes of the sEPSCs or the age of the
      culture. To identify whether the absence of stimulus-evoked response was caused
      either by conduction failure of excitation along the axons or by impairment of
      the release machinery that links the terminal depolarization to vesicle
      exocytosis, we examined whether high K+ and hypertonic solutions could facilitate
      the spontaneous release of transmitters. Although the hypertonic solution
      increased the spontaneous release in all cells tested (n = 18), the high K+
      solution had a differential effect in increasing spontaneous release, i.e., the
      cells with larger evoked responses were more readily facilitated by the high K+
      solution. Because the high K+ solution induced depolarization of presynaptic
      terminals, the present results indicated that the smaller evoked responses were
      due to the larger number of impaired or "silent" presynaptic terminals that were
      unable to link presynaptic depolarization to transmitter release. In summary, the
      present experiments provided evidence that at least some of the presynaptic
      terminals are silent in response to stimuli, while remaining spontaneously active
      at the same time. Because this phenomenon is due to the lack of sensitivity to
      depolarization at the terminals, these synaptic terminals seem incapable of
      linking terminal depolarization to transmitter release.

PMID- 9163395
TI  - Visualization of calcium influx through channels that shape the burst and tonic
      firing modes of thalamic relay cells.
AB  - Thalamic neurons have two firing modes: "tonic" and "burst." During burst mode,
      both low-threshold (LT) and high-threshold (HT) calcium channels are activated,
      while in tonic mode, only the HT-type of calcium channel is activated. The
      calcium signals associated with each firing mode were investigated in rat
      thalamic slices using whole cell patch clamping and confocal calcium imaging.
      Action potentials were induced by direct current injection into thalamic relay
      cells loaded with a fluorescent calcium indicator. In both tonic and burst firing
      modes, large calcium signals were recorded throughout the soma and proximal
      dendrites. To map the distribution of the channels mediating these calcium
      fluxes, LT and HT currents were independently activated using specific voltage
      clamp protocols. We focused on the proximal region of the cell (up to 50 microm
      from the soma) because it appeared to be well clamped. For a voltage pulse of a
      given size, the largest calcium signals were observed in the proximal dendrites
      with smaller signals occurring in the soma and nucleus. This was true for both LT
      and HT signals. Rapid imaging, using one-dimensional linescans, was used to more
      precisely localize the calcium influx. For both LT and HT channels, calcium
      influx occurred simultaneously throughout all imaged regions including the soma
      and proximal dendrites. The presence of sizable calcium signals in the dendrites,
      soma, and nucleus during both firing modes, and the presence of LT calcium
      channels in the proximal dendrite where sensory afferents synapse, have
      implications for both the electrical functioning of relay cells and the
      transmission of sensory information to cortex.

PMID- 9163396
TI  - Convergent chemical and electrical synaptic inputs from proprioceptive afferents
      onto an identified intersegmental interneuron in the crayfish.
AB  - Synaptic transmission between proprioceptive afferents from a chordotonal organ
      in the tailfan of the crayfish and an identified ascending interneuron,
      interneuron A, in the terminal abdominal ganglion was analyzed. Interneuron A is
      part of a disynaptic pathway from primary afferent neurons to the lateral giant
      interneuron involved in producing the characteristic ballistic escape behavior of
      crayfish. Interneuron A received short and long latency excitatory postsynaptic
      potentials (EPSPs) from chordotonal afferents. Short latency EPSPs occurred with
      little central synaptic delay, were unchanged by hyperpolarizing current
      injection of -2 nA, and remained at a constant amplitude when the nervous system
      was bathed in saline with a low calcium concentration or saline containing the
      nicotinic antagonist curare. These EPSPs are thus thought to be mediated by
      electrical transmission. Longer latency potentials were increased in amplitude by
      hyperpolarizing current injection, reduced in amplitude when the nervous system
      was bathed in low-calcium saline, and also reduced by bath application of saline
      containing curare. These potentials are thus thought to be mediated by chemical
      transmission. The functional significance of the dual modes of transmission at a
      key synapse in the escape circuitry is discussed.

PMID- 9163397
TI  - Inhibitory effects evoked from the anterior hypothalamus are selective for the
      nociceptive responses of dorsal horn neurons with high- and low-threshold inputs.
AB  - The aim of the present study was to examine the selectivity of descending control
      of nociceptive information in the spinal dorsal horn following neuronal
      activation at "pressor" sites in the anterior hypothalamus. Extracellular single
      unit activity was recorded from 11 dorsal horn neurons in the lower lumbar spinal
      cord of anesthetized rats. Neurons selected for investigation were those that
      responded to noxious (pinch and radiant heat >46 degrees C) and nonnoxious (prod,
      stroke, and/or brush) stimulation within their cutaneous receptive fields on the
      ipsilateral hind paw. These are referred to as Class 2 neurons. Micropipettes
      were inserted stereotaxically into the anterior hypothalamus at sites where
      injection of the excitatory amino acid L-homocysteic acid (L-HCA) evoked
      increases in arterial blood pressure. The effects of microinjection of L-HCA at
      "pressor" sites in the anterior hypothalamus were then tested on the responses of
      Class 2 neurons to noxious and nonnoxious stimulation of their excitatory
      receptive fields. The high-threshold (pinch and/or radiant heat) responses of 7/7
      Class 2 neurons tested were inhibited by an average of 66.3 +/- 8.8% (mean +/-
      SE) by neuronal activation at hypothalamic pressor sites. The low-threshold
      (prod) responses of 10/10 Class 2 neurons tested were not inhibited by neuronal
      activation at hypothalamic pressor sites; in 6 of these cells the response to low
      intensity stimulation was increased by between 4 and 20%. Control injections of
      the inhibitory amino acid gamma-aminobutyric acid (GABA) at the same hypothalamic
      pressor sites had no significant effects on arterial blood pressure or neuronal
      activity. With regard to sensory processing in the spinal cord, these data
      suggest that descending inhibitory control that originates from neurons in
      pressor regions of the anterior hypothalamus is highly selective for nociceptive
      inputs to Class 2 neurons.

PMID- 9163398
TI  - Response variability and timing precision of neuronal spike trains in vivo.
AB  - We report that neuronal spike trains can exhibit high, stimulus-dependent
      temporal precision even while the trial-to-trial response variability, measured
      in several traditional ways, remains substantially independent of the stimulus.
      We show that retinal ganglion cells and neurons in the lateral geniculate nucleus
      (LGN) of cats in vivo display both these aspects of firing behavior, which have
      previously been reported to be contradictory. We develop a simple model that
      treats neurons as "leaky" integrate-and-fire devices and show that it, too, can
      exhibit both behaviors. We consider the implications of our findings for the
      problem of neural coding.

PMID- 9163399
TI  - Animal model explains the origins of the cranial dystonia benign essential
      blepharospasm.
AB  - The current study demonstrates that combining two mild alterations to the rat
      trigeminal reflex blink system reproduces the symptoms of benign essential
      blepharospasm, a cranial dystonia characterized by uncontrollable spasms of
      blinking. The first modification, a small striatal dopamine depletion, reduces
      the tonic inhibition of trigeminal reflex blink circuits. The second alteration,
      a slight weakening of the lid-closing orbicularis oculi muscle, begins an
      adaptive increase in the drive on trigeminal sensory-motor blink circuits that
      initiates blepharospasm. By themselves, neither of these modifications causes
      spasms of lid closure, but combined, they induce bilateral forceful blinking and
      spasms of lid closure. A two-factor model based on these rodent experiments may
      explain the development of benign essential blepharospasm in humans. The first
      factor, a subclinical loss of striatal dopamine, creates a permissive environment
      within the trigeminal blink circuits. The second factor, an external ophthalmic
      insult, precipitates benign essential blepharospasm. This two-factor model may
      also be applicable to the genesis of other cranial dystonias.

PMID- 9163400
TI  - Distinct patterns of motor unit behavior during muscle spasms in spinal cord
      injured subjects.
AB  - Surface electromyograms (EMG) and force were recorded during repeated involuntary
      spasms of paralyzed triceps surae muscles of four men with chronic cervical
      spinal cord injury. The firing rates of 78 medial gastrocnemius (MG) motor units
      also were recorded intramuscularly with tungsten microelectrodes. Spasms
      typically involved a relatively rapid rise, then a more gradual fall in triceps
      surae EMG and torque. Motor unit firing rates either increased and then decreased
      with the spasm intensity (54%) or were relatively constant (26%), firing mainly
      at 2-10 Hz. The remaining units (20%) produced trains that included one or
      several doublets. Mean peak spasm firing rates were 18 +/- 9 Hz (mean +/- SD) for
      rate modulated units and 11 +/- 10 Hz for units with little or no rate
      modulation. Some motor units fired at rates comparable with those recorded
      previously during maximum voluntary contractions performed by intact subjects.
      Others fired at rates below the minimum usually seen when normal units are first
      recruited (< 6 Hz). Doublets (interspike interval < 10 ms) often repeated every
      123-333 ms, or were interspersed in trains firing at low steady rates (< 11 Hz).
      This study shows that rate coding for many motor units appears to be similar
      whether descending motor input is intact or whether it has been reduced severely
      by spinal cord injury. In contrast, rate modulation in other units appears to
      depend mainly on voluntary motor commands.

PMID- 9163401
TI  - Bidirectional associative plasticity of unitary CA3-CA1 EPSPs in the rat
      hippocampus in vitro.
AB  - Associative long-term potentiation (LTP) and depression of compound and unitary
      CA3-CA excitatory postsynaptic potentials (EPSPs) were investigated in rat
      hippocampal slice cultures. The induction of LTP with synchronous pairing of
      synaptic activation and postsynaptic depolarization resulted in an increase in
      the amplitude of EPSPs to the same absolute level, regardless of whether the
      input was naive or had been previously depressed by asynchronous pairing of pre-
      and postsynaptic activity. Saturated LTP of compound and unitary EPSPs was
      reversed by asynchronous pairing and could be reinduced by synchronous pairing.
      The likelihood that an action potential in a presynaptic CA3 cell failed to
      trigger an unitary EPSP in a postsynaptic CA1 cell decreased after induction of
      associative potentiation and increased after induction of associative
      depotentiation. These changes in the rate of transmission failures were
      accompanied by large changes in the amplitude of nonfailure EPSPs. We conclude
      that the same CA3-CA1 synapses can alternatively undergo associative potentiation
      and depression, perhaps through opposite changes in a single expression
      mechanism.

PMID- 9163402
TI  - Urine-derived compound evokes membrane responses in mouse vomeronasal receptor
      neurons.
AB  - Sensory neurons of the vomeronasal organ (VNO) are thought to detect species
      specific chemical signals important for reproductive function. The electrical
      properties of VNO neurons have begun to be characterized in a variety of species;
      however, the response of VNO neurons to possible physiological ligands has not
      yet been reported. One physiological effector, dehydro-exo-brevicomin (DHB), is
      found in the urine of intact male mice and affects the estrous cycle of female
      mice. In the present study, dissociated VNO neurons were voltage- or current
      clamped and their response to DHB was determined. Approximately 26% of VNO
      neurons responded to DHB with an outward current at negative holding potentials;
      the current reversed at approximately +4 mV. Application of DHB in current-clamp
      mode produced membrane hyperpolarization and/or a reduction in the firing of
      action potentials. Because membrane conductance was shown to be decreased during
      application of DHB, the results suggest that the outward current associated with
      DHB application is a reflection of a reduction in inward current caused by
      closing an ion channel. This study provides the first evidence that a compound
      found in male urine directly affects VNO neurons.

PMID- 9163403
TI  - Short-circuit to be avoided by bioethics committees.

PMID- 9163404
TI  - Clinton sketches out his 'ethical guideposts' for modern biology.

PMID- 9163405
TI  - Calls for human cloning ban 'stem from ignorance'.

PMID- 9163406
TI  - HUGO warning over broad patents on gene sequences.

PMID- 9163407
TI  - Africa spearheads bid for strict rules on biosafety.

PMID- 9163408
TI  - Access law threat to medical merger.

PMID- 9163409
TI  - Ho joins Montagnier in AIDS centres project.

PMID- 9163410
TI  - Who cares what's new?

PMID- 9163411
TI  - Public perception.

PMID- 9163412
TI  - Nepotism and sexism in peer-review.

PMID- 9163413
TI  - HIV-cell fusion. The viral mousetrap.

PMID- 9163414
TI  - Evolutionary ecology. Making life simpler.

PMID- 9163415
TI  - Plant biology. Fixing a symbiotic circle.

PMID- 9163416
TI  - George Wald (1906-97)

PMID- 9163417
TI  - Tyrannosaurs suffered from gout.

PMID- 9163418
TI  - Furtive mating in female chimpanzees.

PMID- 9163419
TI  - Evidence for stone age cranial surgery.

PMID- 9163420
TI  - Structure of ADP x AIF4(-)-stabilized nitrogenase complex and its implications
      for signal transduction.
AB  - The coupling of ATP hydrolysis to electron transfer by the enzyme nitrogenase
      during biological nitrogen fixation is an important example of a nucleotide
      dependent transduction mechanism. The crystal structure has been determined for
      the complex between the Fe-protein and MoFe-protein components of nitrogenase
      stabilized by ADP x AIF4-, previously used as a nucleoside triphosphate analogue
      in nucleotide-switch proteins. The structure reveals that the dimeric Fe-protein
      has undergone substantial conformational changes. The beta-phosphate and AIF4-
      groups are stabilized through intersubunit contacts that are critical for
      catalysis and the redox centre is repositioned to facilitate electron transfer.
      Interactions in the nitrogenase complex have broad implications for signal and
      energy transduction mechanisms in multiprotein complexes.

PMID- 9163421
TI  - Petrological evidence for shock melting of carbonates in the martian meteorite
      ALH84001.
AB  - The meteorite ALH84001--a shocked igneous rock of probable martian origin
      contains chemically and isotopically heterogeneous carbonate globules, associated
      with which are organic and inorganic structures that have been interpreted as
      possible fossil remains of ancient martian biota. A critical assumption
      underlying this suggestion is that the carbonates formed from low-temperature
      fluids penetrating the cracks and voids of the host rock. Here we report
      petrological studies of ALH84001 which investigate the effects of shock on the
      various mineralogical components of the rock. We find that carbonate, plagioclase
      and silica were melted and partly redistributed by the same shock event
      responsible for the intense local crushing of pyroxene in the meteorite. Texture
      and compositional data show that, during the period of shock decompression,
      monomineralic melts were injected into pyroxene fractures that were subsequently
      cooled and resealed within seconds. Our results therefore suggest that the
      carbonates in ALH84001 could not have formed at low temperatures, but instead
      crystallized from shock-melted material; this conclusion weakens significantly
      the arguments that these carbonates could host the fossilized remnants of
      biogenic activity.

PMID- 9163422
TI  - Residue-based control of helix shape in beta-peptide oligomers.
AB  - Proteins and RNA are unique among known polymers in their ability to adopt
      compact and well-defined folding patterns. These two biopolymers can perform
      complex chemical operations such as catalysis and highly selective recognition,
      and these functions are linked to folding in that the creation of an active site
      requires proper juxtaposition of reactive groups. So the development of new types
      of polymeric backbones with well-defined and predictable folding propensities
      ('foldamers') might lead to molecules with useful functions. The first step in
      foldamer development is to identify synthetic oligomers with specific secondary
      structural preferences. Whereas alpha-amino acids can adopt the well-known alpha
      helical motif of proteins, it was shown recently that beta-peptides constructed
      from carefully chosen beta-amino acids can adopt a different, stable helical
      conformation defined by interwoven 14-membered-ring hydrogen bonds (a 14-helix;
      Fig. 1a). Here we report that beta-amino acids can also be used to design beta
      peptides with a very different secondary structure, a 12-helix (Fig. 1a). This
      demonstrates that by altering the nature of beta-peptide residues, one can exert
      rational control over the secondary structure.

PMID- 9163423
TI  - Trade-off-invariant rules for evolutionarily stable life histories.
AB  - Optimization models have been widely and successfully used in evolutionary
      ecology to predict the attributes of organisms. Most such models maximize
      darwinian fitness in the face of trade-offs and constraints; the numerical
      results usually depend on the exact form of the trade-offs or constraints. But
      not always: for example, earlier work predicted that the optimal range in
      offspring size ought to show a - 1 scaling with small litter size, independent of
      most details of the underlying offspring-survival/ offspring-size trade-off
      relation. Here I report that in non-growing (stationary), age-structured
      populations, three major life-history attributes (age at first breeding, size of
      an offspring in large litters, and reproductive effort) are likely to evolve to
      equilibrium values that satisfy a universal numerical rule; the underlying trade
      off will have a slope of - 1 at the optimum, independent of most other aspects of
      the trade-off. Each of these three attributes can be viewed as an allocation
      problem between just two alternatives; the trade-off is then between having more
      of one alternative and less of the other. The slope of the trade-off is simply
      the slope of the curve of allowed combinations of the two alternatives. The
      theory predicts that natural selection will push to an equilibrium where the
      slope is always - 1. The economic structure is the same as that which underlies
      evolution of the sex ratio where the two alternatives are sons and daughters.

PMID- 9163424
TI  - Molecular basis of symbiosis between Rhizobium and legumes.
AB  - Access to mineral nitrogen often limits plant growth, and so symbiotic
      relationships have evolved between plants and a variety of nitrogen-fixing
      organisms. These associations are responsible for reducing 120 million tonnes of
      atmospheric nitrogen to ammonia each year. In agriculture, independence from
      nitrogenous fertilizers expands crop production and minimizes pollution of water
      tables, lakes and rivers. Here we present the complete nucleotide sequence and
      gene complement of the plasmid from Rhizobium sp. NGR234 that endows the
      bacterium with the ability to associate symbiotically with leguminous plants. In
      conjunction with transcriptional analyses, these data demonstrate the presence of
      new symbiotic loci and signalling mechanisms. The sequence and organization of
      genes involved in replication and conjugal transfer are similar to those of
      Agrobacterium, suggesting a recent lateral transfer of genetic information.

PMID- 9163425
TI  - Task difficulty and the specificity of perceptual learning.
AB  - Practising simple visual tasks leads to a dramatic improvement in performing
      them. This learning is specific to the stimuli used for training. We show here
      that the degree of specificity depends on the difficulty of the training
      conditions. We find that the pattern of specificities maps onto the pattern of
      receptive field selectivities along the visual pathway. With easy conditions,
      learning generalizes across orientation and retinal position, matching the
      spatial generalization of higher visual areas. As task difficulty increases,
      learning becomes more specific with respect to both orientation and position,
      matching the fine spatial retinotopy exhibited by lower areas. Consequently, we
      enjoy the benefits of learning generalization when possible, and of fine grain
      but specific training when necessary. The dynamics of learning show a
      corresponding feature. Improvement begins with easy cases (when the subject is
      allowed long processing times) and only subsequently proceeds to harder cases.
      This learning cascade implies that easy conditions guide the learning of hard
      ones. Taken together, the specificity and dynamics suggest that learning proceeds
      as a countercurrent along the cortical hierarchy. Improvement begins at higher
      generalizing levels, which, in turn, direct harder-condition learning to the
      subdomain of their lower-level inputs. As predicted by this reverse hierarchy
      model, learning can be effective using only difficult trials, but on condition
      that learning onset has previously been enabled. A single prolonged presentation
      suffices to initiate learning. We call this single-encounter enabling effect
      'eureka'.

PMID- 9163426
TI  - Pax6 is required for differentiation of glucagon-producing alpha-cells in mouse
      pancreas.
AB  - The functional unit of the endocrine pancreas is the islet of Langerhans. Islets
      are nested within the exocrine tissue of the pancreas and are composed of alpha-,
      beta-, delta- and gamma-cells. beta-Cells produce insulin and form the core of
      the islet, whereas alpha-, delta- and gamma-cells are arranged at the periphery
      of the islet and secrete glucagon, somatostatin and a pancreatic polypeptide,
      respectively. Little is known about the molecular and genetic factors regulating
      the lineage of the different endocrine cells. Pancreas development is known to be
      abolished in Pdx1-mutant mice and Pax4 mutants lack insulin-producing beta-cells.
      Here we show that the paired-box gene Pax6 is expressed during the early stages
      of pancreatic development and in mature endocrine cells. The pancreas of Pax6
      homozygous mutant mice lack glucagon-producing cells, suggesting that Pax6 is
      essential for the differentiation of alpha-cells. As mice lacking Pax4 and Pax6
      fail to develop any mature endocrine cells, we conclude that both Pax genes are
      required for endocrine fate in the pancreas.

PMID- 9163427
TI  - Expression cloning and characterization of a renal electrogenic Na+/HCO3-
      cotransporter.
AB  - Bicarbonate transporters are the principal regulators of pH in animal cells, and
      play a vital role in acid-base movement in the stomach, pancreas, intestine,
      kidney, reproductive system and central nervous system. The functional family of
      HCO3- transporters includes Cl- -HCO3- exchangers, three Na+/HCO3-
      cotransporters, a K+/HCO3- cotransporter, and a Na+-driven Cl- -HCO3- exchanger.
      Molecular information is sparse on HCO3- transporters, apart from Cl- -HCO3-
      exchangers ('anion exchangers'), whose complementary DNAs were cloned several
      years ago. Attempts to clone other HCO3- transporters, based on binding of
      inhibitors, protein purification or homology with anion exchangers, have so far
      been unsuccessful. Here we monitor the intracellular pH and membrane voltage in
      Xenopus oocytes to follow the expression of the most electrogenic transporter
      known: the renal 1:3 electrogenic Na+/HCO3- cotransporter from the salamander
      Ambystoma tigrinum. We now report the successful cloning and characterization of
      a cDNA encoding a cation-coupled HCO3- transporter. The encoded protein is 1,035
      amino acids long with several potential membrane-spanning domains. We show that
      when it is expressed in Xenopus oocytes, this protein is electrogenic, Na+ and
      HCO3- dependent, and blocked by the anion-transport inhibitor DIDS, and conclude
      that it is the renal electrogenic sodium bicarbonate cotransporter (NBC).

PMID- 9163428
TI  - Overexpression of the HDL receptor SR-BI alters plasma HDL and bile cholesterol
      levels.
AB  - The risk of atherosclerosis, a leading cause of cardiovascular disease and death,
      is inversely related to plasma levels of high-density lipoprotein (HDL)
      cholesterol, although the mechanism of this protective effect is unclear. The
      class B scavenger receptor, SR-BI, is the first HDL receptor to be well defined
      at a molecular level and is a mediator of selective cholesterol uptake in vitro.
      It is expressed most abundantly in steroidogenic tissues, where it is
      coordinately regulated with steroidogenesis by adrenocorticotropic hormone
      (ACTH), human chorionic gonadotropin (hCG) and oestrogen, and in the liver, where
      its expression in rats is suppressed by oestrogen. Here we show that adenovirus
      mediated, hepatic overexpression of SR-BI in mice on both sinusoidal and
      canalicular surfaces of hepatocytes results in the virtual disappearance of
      plasma HDL and a substantial increase in biliary cholesterol. SR-BI may directly
      mediate these effects by increasing hepatic HDL cholesterol uptake or by
      increasing cholesterol secretion into bile, or both. These results indicate that
      SR-BI may be important in hepatic HDL metabolism, in determining plasma HDL
      concentrations, and in controlling cholesterol concentrations in bile, and thus
      may influence the development and progression of atherosclerosis and gallstone
      disease.

PMID- 9163429
TI  - Repression of the CDK activator Cdc25A and cell-cycle arrest by cytokine TGF-beta
      in cells lacking the CDK inhibitor p15.
AB  - The activity of the cyclin-dependent kinases (CDKs) that control cell growth and
      division can be negatively regulated by tyrosine phosphorylation or by the
      binding of various CDK inhibitors. Whereas regulation by tyrosine phosphorylation
      is well documented in CDKs that function during mitosis, little is known about
      its role in the regulation of CDKs that act in the G1 phase of the cell cycle. In
      contrast, much evidence has accumulated on the regulation of G1 CDKs by CDK
      inhibitors. The cytokine TGF-beta inhibits growth by causing cell-cycle arrest as
      a result of increasing the concentration of the Cdk4/6 inhibitor p15(INK4B/MTS2)
      (refs 3, 4). Here we report that TGF-beta can also cause the inhibition of Cdk4
      and Cdk6 by increasing their level of tyrosine phosphorylation. Tyrosine
      phosphorylation and inactivation of Cdk4/6 in a human mammary epithelial cell
      line are shown to result from the ability of TGF-beta to repress expression of
      the CDK tyrosine phosphatase Cdc25A. Repression of Cdc25A and induction of p15
      are independent effects mediating the inhibition of Cdk4/6 by TFG-beta.

PMID- 9163430
TI  - Myc and Ras collaborate in inducing accumulation of active cyclin E/Cdk2 and E2F.
AB  - Considerable evidence points to a role for G1 cyclin-dependent kinase (CDK) in
      allowing the accumulation of E2F transcription factor activity and induction of
      the S phase of the cell cycle. Numerous experiments have also demonstrated a
      critical role for both Myc and Ras activities in allowing cell-cycle progression.
      Here we show that inhibition of Ras activity blocks the normal growth-dependent
      activation of G1 CDK, prevents activation of the target genes of E2F, and results
      in cell-cycle arrest in G1. We also show that Ras is essential for entry into the
      S phase in Rb+/+ fibroblasts but not in Rb-/- fibroblasts, establishing a link
      between Ras and the G1 CDK/Rb/E2F pathway. However, although expression of Ras
      alone will not induce G1 CDK activity or S phase, coexpression of Ras with Myc
      allows the generation of cyclin E-dependent kinase activity and the induction of
      S phase, coincident with the loss of the p27 cyclin-dependent kinase inhibitor
      (CKI). These results suggest that Ras, along with the activation of additional
      pathways, is required for the generation of G1 CDK activity, and that activation
      of cyclin E-dependent kinase in particular depends on the cooperative action of
      Ras and Myc.

PMID- 9163431
TI  - Atomic structure of the ectodomain from HIV-1 gp41.
AB  - Fusion of viral and cellular membranes by the envelope glycoprotein gp120/gp41
      effects entry of HIV-1 into the cell. The precursor, gp160, is cleaved post
      translationally into gp120 and gp41 which remain non-covalently associated.
      Binding to both CD4 and a co-receptor leads to the conformational changes in
      gp120/gp41 needed for membrane fusion. We used X-ray crystallography to determine
      the structure of the protease-resistant part of a gp41 ectodomain solubilized
      with a trimeric GCN4 coiled coil in place of the amino-terminal fusion peptide.
      The core of the molecule is found to be an extended, triple-stranded alpha
      helical coiled coil with the amino terminus at its tip. A carboxy-terminal alpha
      helix packs in the reverse direction against the outside of the coiled coil,
      placing the amino and carboxy termini near each other at one end of the long rod.
      These features, and the existence of a similar reversal of chain direction in the
      fusion pH-induced conformation of influenza virus HA2 and in the transmembrane
      subunit of Moloney murine leukaemia virus (Fig. 1a-d), suggest a common mechanism
      for initiating fusion.

PMID- 9163432
TI  - Direct detection and identification of Pseudomonas aeruginosa in clinical samples
      such as skin biopsy specimens and expectorations by multiplex PCR based on two
      outer membrane lipoprotein genes, oprI and oprL.
AB  - A multiplex PCR test based on the simultaneous amplification of two lipoprotein
      genes, oprI and oprL, was designed and evaluated for its ability to directly
      detect fluorescent pseudomonads (amplification of oprI open reading frame, 249
      bp) and Pseudomonas aeruginosa (amplification of oprL open reading frame, 504 bp)
      in clinical material. A collection of reference strains including 20 different
      species of fluorescent pseudomonads was tested. Positive PCR results for both
      genes were observed only for P. aeruginosa isolates (n = 150), including strains
      of clinical and environmental origin, while only one gene, oprI, was amplified
      from the other fluorescent pseudomonads. All other bacteria tested (n = 15) were
      negative by the amplification test. The lower detection level for P. aeruginosa
      was estimated to be 10(2) cells/ml. Preliminary evaluation on testing skin biopsy
      specimens from patients with burns (n = 14) and sputum samples from cystic
      fibrosis patients (n = 49) and other patients (n = 19) showed 100% sensitivity
      and 74% specificity in comparison with culture. This multiplex PCR assay appears
      promising for the rapid and sensitive detection of P. aeruginosa in clinical
      specimens. Further evaluation of its specificity in longitudinal clinical studies
      is warranted.

PMID- 9163433
TI  - Vector potential of houseflies (Musca domestica) for Helicobacter pylori.
AB  - The mode of transmission of Helicobacter pylori is unknown. Since viable bacteria
      have been shown to be excreted in feces from infected individuals and houseflies
      habitually develop and feed on excrement, we hypothesized that flies ingest and
      harbor H. pylori and, in turn, contaminate the human environment. This study
      examined the possible vector potential of houseflies (Musca domestica) for H.
      pylori. Caged houseflies were exposed to freshly grown H. pylori on agar plates.
      After a 6-h feeding period, the plates were removed and were replaced with
      sterile petri dishes containing a droplet of sterile brucella broth. At regular
      intervals, small numbers of houseflies were removed for microbiological and
      histological analysis, and the petri dishes were replaced with fresh sterile
      plates with fresh drops of brucella broth. The flies' bodies, the flies'
      dissected alimentary tracts, and excreta on the petri dishes were cultured for H.
      pylori, whose identity was confirmed by the urease, catalase, and oxidase
      reactions and Gram staining. In contrast to control flies, viable H. pylori could
      be isolated from external surfaces for up to 12 h and from gut and excreta for as
      long as 30 h after the initial feeding period. After 30 h other gram-negative
      bacteria overgrew the cultures of samples from all locations tested, rendering
      the selective culture of H. pylori colonies impossible. Histological analysis
      revealed Helicobacter-like organisms in the gut lumen and attached to intestinal
      epithelial cells. We conclude that houseflies can harbor viable H. pylori on
      their bodies and in their intestinal tracts. They are also able to disseminate
      viable H. pylori in excreta, and they may therefore present a significant
      reservoir and be a vector in the transmission of H. pylori.

PMID- 9163435
TI  - Variability in susceptibilities of Haemophilus influenzae to clarithromycin and
      azithromycin due to medium pH.
AB  - The National Committee for Clinical Laboratory Standards (NCCLS) methods for
      susceptibility testing of Haemophilus influenzae in Haemophilus test medium allow
      a pH range of 7.2 to 7.4. However, it is known that bacteria may appear to be
      less susceptible to macrolides at lower pHs. Forty-four strains of H. influenzae
      were tested for their susceptibilities to clarithromycin and azithromycin by the
      disk diffusion and broth microdilution methods. The isolates appeared to be less
      susceptible at pH 7.2 than at pH 7.4 by both methods. Clarithromycin was less
      active at pH 7.2 against 43% of the isolates by the disk diffusion method and
      against 52% of the isolates by the broth microdilution method. Similarly,
      azithromycin was less active at pH 7.2 against 41 and 45% of the isolates by the
      disk diffusion and broth microdilution methods, respectively. Forty-two isolates
      were classified as clarithromycin susceptible and all isolates were classified as
      azithromycin susceptible by the disk diffusion method, regardless of the medium
      pH. However, only 21 isolates were clarithromycin susceptible at pH 7.2 and 34
      isolates were susceptible at pH 7.4 by the broth microdilution method, even
      though quality control results indicated valid testing at both pHs. This study
      indicated that the results of tests of the susceptibility of H. influenzae with
      clarithromycin and azithromycin are highly dependent on the pH of the medium.
      Test results and their interpretations varied even when the medium pH was within
      the NCCLS-approved range and, coupled with the current NCCLS breakpoint of 8
      microg/ml in the case of clarithromycin, may explain some of the observed
      discordances between the disk diffusion and broth microdilution methods.

PMID- 9163434
TI  - PCR detection of human papillomavirus: comparison between MY09/MY11 and GP5+/GP6+
      primer systems.
AB  - Human papillomavirus (HPV) is an etiologic agent of cervical cancer and is the
      most common sexually transmitted disease in women. PCR amplification of HPV
      genomes is the most sensitive method for the detection of cervicovaginal HPV. We
      have compared the two most commonly used PCR primer sets, MY09/MY11 (MY-PCR) and
      GP5+/GP6+ (GP+-PCR), for the detection of HPV DNA in cervicovaginal lavage
      samples from 208 women. Oligonucleotide probes for 39 different HPV types were
      used. Both primer sets amplified a wide spectrum of HPV genotypes and detected
      similar overall prevalences of 45% (94 of 208) and 43% (89 of 208), respectively.
      The MY-PCR system detected 27 of 30 (90%) samples with multiple HPV types,
      whereas the GP+-PCR system detected 14 of 30 (47%) samples with multiple HPV
      types. Differences in the detection of HPV types 35, 53, and 61 were noted
      between the two primer systems. Serial dilution of plasmid templates indicated a
      3-log decrease in the amplification of HPV type 35 by MY-PCR and HPV types 53 and
      61 by GP+-PCR. These results indicate that although the MY-PCR and GP+-PCR
      identified nearly equivalent prevalences of HPV in a set of clinical samples,
      differences in the detection of specific types and infections with multiple types
      were found. Differences in the sensitivities and characteristics of the PCR
      systems for the detection of HPV within clinical samples should be considered
      when comparing data between studies and/or in designing new studies or clinical
      trials.

PMID- 9163436
TI  - Molecular epidemiology of antibiotic resistance of Salmonella enteritidis during
      a 7-year period in Greece.
AB  - A significant increase in the frequency of isolation of Salmonella enteritidis
      has been observed during recent years in Greece, parallelled by an increasing
      rate of resistance of this organism to antibiotics. A substantial proportion of
      ampicillin- and doxycycline-resistant isolates exhibited cross-resistance to
      drugs of other classes, such as sulfonamides and streptomycin. Isolates of human
      origin were overall less resistant than those of animal or food-feed origin.
      Indeed, strains associated with animal infections were characterized by the
      highest rates of resistance to several antibiotics. These phenotypic data were
      correlated with genotypic information concerning two distinct populations:
      isolates from all sources that were resistant only to ampicillin, the drug toward
      which resistance rates were highest, and a control group of sensitive isolates.
      Ampicillin resistance was due to a 34-MDa conjugative plasmid. DNA fingerprinting
      by macrorestriction of genomic DNA revealed two types, A and B, common to both
      ampicillin-resistant and -sensitive strains, with 80 to 90% of strains being of
      type A. However, a third type, C, was specific for the sensitive population,
      representing 17% of those strains. Therefore, although the majority of resistant
      isolates were genetically related to sensitive ones, there existed a susceptible
      clone which had not acquired any resistance traits.

PMID- 9163437
TI  - PCR and probe-PCR assays to monitor broodstock Atlantic salmon (Salmo salar L.)
      ovarian fluid and kidney tissue for presence of DNA of the fish pathogen
      Renibacterium salmoninarum.
AB  - A simple, rapid PCR assay for the identification of Renibacterium salmoninarum in
      Atlantic salmon (Salmo salar L.) tissues detected DNA extracted from between 4
      and 40 bacterial cells. PCR was at least as sensitive as culture when it was used
      to identify subclinically infected fish experimentally challenged with R.
      salmoninarum. However, PCR identified much higher numbers of kidney tissue and
      ovarian fluid samples from commercially reared broodstock fish to be positive for
      R. salmoninarum than did culture. This difference may be due to the antibiotic
      chemotherapy of broodstock fish used by the industry in 1994 to control the
      vertical transmission of R. salmoninarum. A much closer relationship between PCR
      and culture results was observed for ovarian fluid samples collected from
      broodstock fish in 1993. Also, PCR scored a much higher percentage of kidney
      tissue samples than ovarian fluid samples from 1994 broodstock fish positive for
      R. salmoninarum, which may reflect the uneven distribution of the pathogen in
      different fish tissues. Inclusion of a nested probe to identify the PCR-positive
      1994 ovarian fluid samples increased the sensitivity of detection to between one
      and four cells and the number of samples that scored positive by almost
      threefold. These data indicate that many infected ovarian fluid samples contained
      very low numbers of R. salmoninarum cells and, because almost all these samples
      were culture negative, that PCR may have detected dead or otherwise unculturable
      bacterial cells.

PMID- 9163438
TI  - Prevalence of Bartonella henselae and Bartonella clarridgeiae in stray cats.
AB  - The aim of the present work was to determine by blood culture the prevalence of
      blood infection with Bartonella species in a well-defined, European, urban stray
      cat population. Therefore, 94 stray cats were trapped from 10 cat colonies. Blood
      samples of these cats were cultured on both blood agar and liquid medium in order
      to raise the likelihood of bacterial detection. Fifty blood samples (53%) gave a
      positive culture result for Bartonella species. Isolate identification was
      performed by sequencing the first 430 bases of the 16S ribosomal DNA. Three types
      of sequences were thus obtained. The first type (17 isolates; 34%) was identical
      to that of B. henselae Houston-1 and the corresponding strains were referred as
      B. henselae type I. The second sequence type (18 isolates; 36%) was identical to
      that initially described as "BA-TF," and the corresponding strains were referred
      to as B. henselae type II. The third sequence type (15 isolates; 30%) was
      identical to that of the Bartonella clarridgeiae type strain (ATCC 51734). Our
      study points out the major role of stray cats as a reservoir of Bartonella spp.
      which can be transmitted to pet cats and, consequently, to humans. The study also
      highlights the high prevalence of B. clarridgeiae (16%) in the blood of stray
      cats.

PMID- 9163439
TI  - Comparative analysis of genetic variability among Candida albicans isolates from
      different geographic locales by three genotypic methods.
AB  - The objective of the present study was to conduct a comparative genotypic
      analysis of Candida albicans isolates from the United States, Europe, and
      Southeast Asia to determine whether differences between isolates might be
      associated with geographic locations. The genotypes of 86 unrelated isolates of
      C. albicans (from the United States and Europe) and 26 isolates from Singapore
      were examined by three DNA typing methods. Computer-assisted methods were used to
      analyze the gel patterns for all isolates. A dendrogram based on the overall
      similarity of the patterns obtained by restriction endonuclease analysis (REA)
      with EcoRI clustered the U.S. and European isolates into two major groups (groups
      A and B). The Singaporean isolates demonstrated unique REA profiles, with nine
      isolates having both or neither of the REA-characteristic 3.7- and 4.2-kb bands
      present in groups A and B. By REA profiles, the Singaporean isolates were related
      to each other with similarity values (S(AB)s) of > 0.80, but only one isolate
      mixed with the U.S. and European isolates at this S(AB) (an arbitrary threshold
      for genetic similarity). Randomly amplified polymorphic DNA (RAPD) analysis
      generated DNA profiles that clustered the C. albicans isolates into approximately
      the same number of distinct typing groups as REA. However, isolates identical to
      each other by REA were generally different from each other by RAPD analysis. In a
      composite dendrogram prepared from the results obtained by RAPD analysis, the
      isolates from the United States and Europe clustered in major groups with S(AB)s
      of > 0.85, while Singaporean isolates connected to these clusters at S(AB)s of >
      or = 0.75. Pulsed-field gel electrophoresis was less discriminatory, discerning
      about one-third as many distinct subtypes as REA or RAPD analysis; the
      Singaporean isolates were distributed randomly with the U.S. and European
      isolates. These results suggest that a high degree of genetic diversity exists
      between C. albicans isolates from Southeast Asia and those from the United States
      and Europe.

PMID- 9163440
TI  - Rapid identification and fingerprinting of Candida krusei by PCR-based
      amplification of the species-specific repetitive polymorphic sequence CKRS-1.
AB  - A PCR method was developed to identify and fingerprint Candida krusei isolates
      simply and rapidly. The primer pair Arno1 and Arno2 was designed to amplify the
      polymorphic species-specific repetitive sequence CKRS-1 (C. krusei repeated
      sequence 1) that we identified in the nontranscribed intergenic regions (IGRs) of
      rRNA genes in C. krusei LMCK31. The specificity, sensitivity, reproducibility,
      and fingerprinting ability of the PCR assay were evaluated. Amplification
      products were obtained from all 131 C. krusei isolates studied. No other yeast
      species of medical importance (n = 26), including species similar to C. krusei,
      species of pathogenic filamentous fungi, or a variety of pathogenic bacteria,
      yielded a PCR product with these primers. This PCR assay allowed for the
      identification of C. krusei in less than 6 h. The PCR assay was sensitive enough
      to detect as little as 10 to 100 fg of C. krusei-purified DNA and proved to be
      reproducible. Since amplification products varied both in number and in molecular
      weight according to the strains, PCR patterns allowed strains to be
      distinguished. To ascertain the epidemiological usefulness of this PCR
      fingerprinting, the patterns of the 131 isolates were compared. A total of 95
      types which corresponded to 95 independent strains were delineated
      (discriminatory power = 1 with n = 95). Comparison of the results of PCR
      fingerprinting and those of fingerprinting with the CkF1,2 probe showed that they
      concurred. In addition, this work yields insights into the mechanisms involved in
      generating polymorphisms in the IGRs of C. krusei. Since this method is simpler
      and faster than established identification and genotyping methods of this
      important pathogenic species, it is a critical improvement for clinical
      microbiology laboratories relevant not only to diagnosis but also to
      epidemiology.

PMID- 9163441
TI  - Equally high prevalences of infection with cagA-positive Helicobacter pylori in
      Chinese patients with peptic ulcer disease and those with chronic gastritis
      associated dyspepsia.
AB  - Approximately 60% of Helicobacter pylori isolates in the Western world possess
      the cytotoxin-associated gene A (cagA). cagA-positive H. pylori is found to be
      associated with peptic ulcer disease (PUD) and gastric adenocarcinoma. To
      investigate the cagA status of H. pylori isolates from Chinese patients with PUD
      and chronic gastritis (CG), H. pylori populations from 83 patients, 48 with PUD
      and 35 with CG, were assessed by two different cagA-specific PCRs, Southern
      blotting, and colony hybridization. The combined results from PCR, Southern
      blotting, and colony hybridization indicate a prevalence of cagA-positive H.
      pylori isolates of 98% (47 of 48) among Chinese PUD patients and 100% (35 of 35)
      among Chinese CG patients. Amplification with primer sets 1 and 2 yielded 52 and
      95% of the 82 cagA-positive Chinese H. pylori, respectively. In contrast, the
      sensitivity of cagA-specific PCR for cagA-positive H. pylori isolates from Dutch
      patients with primer set 1 was 92% (112 of 122) and that with primer set 2 was
      91% (50 of 55). The prevalence of cagA-positive H. pylori populations in Chinese
      patients with PUD and CG is almost universally high. Therefore, cagA cannot be
      used as a marker for the presence of PUD in Chinese patients. Our data further
      suggest that allelic variation in cagA may exist and that distinct H. pylori
      genotypes may circulate in China and Western Europe.

PMID- 9163442
TI  - Detection of Treponema pallidum by a sensitive reverse transcriptase PCR.
AB  - Syphilis is diagnosed by serologic testing or by identification of the causative
      agent, Treponema pallidum. The bacterium has historically been detected in
      clinical specimens by dark-field microscopy, immunostaining with polyclonal or
      monoclonal antibodies, or the rabbit inoculation test (RIT). RIT is considered to
      be very sensitive and specific, although it is available only in research
      settings and is not clinically useful due to the length of time required to
      obtain a result. In recent years, several PCR methods have been developed for the
      detection of T. pallidum, but none of these has shown a clear advantage in
      sensitivity over RIT. We have developed a specific and highly sensitive reverse
      transcriptase PCR (RT-PCR) that targets a 366 bp region of the 16S rRNA of T.
      pallidum. This RT-PCR can detect a single organism by Southern analysis when
      whole organisms are diluted and 10(-2) to 10(-3) T. pallidum organisms when RNA
      equivalents are used to make cDNA. The test was demonstrated to detect 10(-2) T.
      pallidum RNA equivalents in cerebrospinal fluid. Twenty different strains of T.
      pallidum, isolated from cerebrospinal fluids, aqueous humor, blood, and chancres,
      were shown to be detectable by this test. This efficient and sensitive technique
      could be more useful than existing methods for detecting very low numbers of
      organisms in clinical samples.

PMID- 9163443
TI  - Detection and identification of fungal pathogens in blood by using molecular
      probes.
AB  - A PCR assay was developed for the detection and identification of Candida and
      Aspergillus species. The design of the oligonucleotide primer pair as well as the
      species-specific probes used for species identification was derived from a
      comparison of the sequences of the 18S rRNA genes of various fungal pathogens.
      The primers targeted a consensus sequence for a variety of fungal pathogens. The
      assay was tested for sensitivity and specificity with 134 fungal and 85 nonfungal
      isolates. To assess clinical applicability, 601 blood samples from four defined
      groups were tested: group A (n = 35), controls; groups B to D (n = 86), patients
      with febrile neutropenia, without fungal colonization (group B; n = 29) and with
      fungal colonization (group C; n = 36); and patients with documented invasive
      fungal infection (IFI) (group D; n = 21). The assay detected and, by species
      specific hybridization, identified most of the clinically relevant Candida and
      Aspergillus species at 1 CFU/ml of blood. Amplification was 100% sensitive for
      all molds and yeasts tested, with Histoplasma capsulatum being the only non
      Aspergillus species hybridizing with the Aspergillus spp. probe. None of 35 group
      A patients and only 3 of 65 group B and C patients were PCR positive. The
      sensitivity of the assay for specimens from patients with IFI (21 patients in
      group D) was 100% if two specimens were tested. For specificity, 3 of 189
      specimens from patients at risk but with negative cultures were positive by the
      assay, for a specificity of 98%. PCR preceded radiological signs by a median of 4
      days (range, 4 to 7 days) for 12 of 17 patients with hepatosplenic candidiasis or
      pulmonary aspergillosis. For the 10 patients with IFI responding to antifungal
      therapy, PCR assays became persistently negative after 14 days of treatment, in
      contrast to the case for 11 patients, who remained PCR positive while not
      responding to antifungal therapy. Thus, the described PCR assay allows for the
      highly sensitive and specific detection and identification of fungal pathogens in
      vitro and in vivo. Preliminary data from the screening of a selected group of
      patients revealed some value in the early diagnosis and monitoring of antifungal
      therapy.

PMID- 9163444
TI  - Fatty acid characterization of rapidly growing pathogenic aerobic actinomycetes
      as a means of identification.
AB  - The fatty acid compositions of 39 type strains and 529 clinical or reference
      strains of pathogenic aerobic actinomycetes were analyzed after standardized
      culture by using the Microbial Identification System (MIS). Library entries for
      each type strain were created by using the MIS Library Generation Software, and
      the fatty acid profiles of clinical and reference strains were compared to these
      library entries. The bacteria separated into two large groups based upon major
      amounts of branched-chain or of saturated or monounsaturated straight-chain fatty
      acids. Identification of isolates was possible by using only the type strains for
      comparison, but fatty acid heterogeneity occurred within most species.

PMID- 9163445
TI  - Detection of Chlamydia trachomatis in male and female urine specimens by using
      the amplified Chlamydia trachomatis test.
AB  - The amplified Chlamydia trachomatis test (AMP-CT; Gen-Probe), a new diagnostic
      test for the detection of Chlamydia trachomatis, was evaluated with urine
      specimens from 1,000 patients visiting the outpatient department for sexually
      transmitted diseases at the University Hospital Rotterdam, Rotterdam, The
      Netherlands, by comparing the results to those of cell culture. From February
      1996 to July 1996, urine samples for the AMP-CT test and urethral swabs for cell
      culture were collected from 544 men, while cervical swabs from 456 women were
      also taken for cell culture. Positive test results were obtained for 130 (13%) of
      the patients. AMP-CT test and cell culture results were discordant for 70 (7%)
      specimens. Analysis of the samples with discordant results was performed by an in
      house PCR. After resolution of the discordant results, the sensitivity,
      specificity, and positive and negative predictive values of the AMP-CT test were
      84.3, 98.8, 89.6, and 98%, respectively, for samples from females and 100, 99.2,
      93.1, and 100%, respectively, for samples from males, while for cell culture
      these values were 72.5, 99.2, 92.5, and 98%, respectively, for samples from
      females and 57.4, 99.0, 86.1, and 95.4%, respectively, for samples from males. We
      conclude that the AMP-CT test is a fast and reliable test for the detection of C.
      trachomatis in urine specimens from females and, in particular, males.

PMID- 9163446
TI  - A new PCR-based seroneutralization assay in cell culture for diagnosis of
      hepatitis E.
AB  - A new method for the serological diagnosis of hepatitis E virus (HEV) infection
      based on neutralization of the virus in cell culture was developed. The test
      involves a short incubation of the virus in the presence of the serum sample to
      be tested and permissive cells. With viral replication being limited and without
      a cytopathic effect, viral growth in cells is evaluated by reverse transcription
      and PCR. The specificity of the test was established by studying sera from
      healthy individuals and patients with hepatitis living in France, where
      autochthonous hepatitis E is unknown. The kinetics and sensitivity of antibody
      detection were evaluated during the experimental infection of monkeys.
      Neutralizing antibodies were found in 79% of patients during an outbreak of
      hepatitis E and in 43% of patients with sporadic, acute non-A, non-B (without
      anti-hepatitic C virus antibodies) hepatitis. This neutralization assay is
      proposed as a confirmatory test for the available enzyme-linked immunosorbent
      assay (ELISA), which is now recognized as giving many false-positive reactions,
      and to improve identification of new hepatitis viruses since false-negative
      reactions with HEV ELISA are also encountered.

PMID- 9163447
TI  - Characterization of Bacteroides forsythus isolates.
AB  - Fifteen Bacteroides forsythus strains freshly isolated from patients with
      periodontitis were used together with three collection strains and one type
      strain for characterization of growth on various media; determination of
      enzymatic profiles, antibiotic susceptibility profiles, 16S rRNA ribotypes,
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) outer
      membrane protein profiles, and pathogenicity; and gas chromatography analysis by
      using a wound chamber model in rabbits. All strains were stimulated by N
      acetylmuramic acid, while one strain needed a further supplement such as yeast
      extract for optimal growth. All strains showed trypsin-like activity. While 10
      different ribotypes were found, the SDS-PAGE profiles revealed similar patterns
      for all strains. All strains were sensitive to penicillin G (MICs, <0.5
      microg/ml), ampicillin (MICs, <1.0 microg/ml), amoxicillin (MICs, <0.38
      microg/ml), metronidazole (MICs, <0.005 microg/ml), tetracycline (MICs, <0.19
      microg/ml), doxycycline (MICs, 0.05 microg/ml), erythromycin (MICs, <0.4
      microg/ml), and clindamycin (MICs, <0.016 microg/ml), while they were less
      sensitive to ciprofloxacin (MICs, <4 microg/ml). B. forsythus did not cause
      abscess formation by monoinoculation. B. forsythus coinoculated with
      Fusobacterium nucleatum ATCC 10953 caused abscess formation in 75% of rabbits,
      while it caused abscess formation in 100% of rabbits when it was coinoculated
      with Porphyromonas gingivalis FDC 381. In the case of the latter combination,
      four of six rabbits died of sepsis after 6 to 7 days, and P. gingivalis and B.
      forsythus were recovered from the heart blood at a proportion of 10:1. B.
      forsythus strains were highly virulent and invasive in combination with P.
      gingivalis.

PMID- 9163448
TI  - Comparison of BACTEC 9240 Peds Plus medium and isolator 1.5 microbial tube for
      detection of Brucella melitensis from blood cultures.
AB  - The sensitivity and time to detection of Brucella melitensis by the BACTEC 9240
      and the Isolator blood culture systems were compared in a prospective volume
      controlled study. Blood sample aliquots, obtained from children with suspected
      brucellosis, were inoculated into a BACTEC 9240 Peds Plus bottle and into an
      Isolator 1.5 Microbial Tube. Overall, 122 pairs of blood samples for culture were
      obtained, and 28 (23%) were positive by at least one method. The BACTEC 9240
      system detected all 28 positive cultures (sensitivity, 100%), and the Isolator
      system detected 22 positive cultures (sensitivity, 79%) (P = 0.023). Among those
      22 cultures positive by both methods, 21 (95%) and 15 (68%) were found to be
      positive within 3 days by the BACTEC and the Isolator systems, respectively; 8
      (36%) were found to be positive at least 1 day earlier by the BACTEC instrument,
      and the remaining 14 were found to be positive by the two systems on the same day
      (P = 0.045). The BACTEC 9240 blood culture system is more sensitive than the
      Isolator system for the detection of B. melitensis and is superior in terms of
      time to detection of the organism.

PMID- 9163449
TI  - Comparison of two automated DNA amplification systems with a manual one-tube
      nested PCR assay for diagnosis of pulmonary tuberculosis.
AB  - Eighty-four specimens of respiratory secretions culture positive for mycobacteria
      (70 positive for Mycobacterium tuberculosis and 14 positive for nontuberculous
      mycobacteria) and 120 culture-negative specimens were evaluated by three DNA
      amplification techniques: a manual in-house single-tube nested PCR (nPCR) and two
      commercial automated assays (the Cobas Amplicor System [aPCR-h] from Roche
      Diagnostic Systems and the Abbott LCx Probe System [aLCx-p] from Abbott
      Laboratories). The overall diagnostic sensitivities of the nPCR, aPCR-h, and aLCx
      p were 77.1, 84.3, and 77.1%, respectively, and the sensitivities were 57.9,
      57.9, and 36.8%, respectively, for smear-negative specimens. Specimens culture
      positive for nontuberculous mycobacteria were negative by all three assays. Eight
      culture-negative specimens which were positive by one or more assays had
      previously been documented by culture to be positive for M. tuberculosis and were
      taken from patients who were treated with antituberculosis agents. Retesting of
      specimens negative by one assay by the other two assays revealed that each test
      had its unique group of negative specimens. When considering the DNA extraction
      and amplification steps of these assays separately, it was found that extracts
      from aPCR-h and aLCx-p were compatible with nPCR amplication, while the two
      automated assays could only amplify extracts processed with their own reagents.
      Limiting dilution analysis revealed that the order of analytical sensitivity was
      nPCR, followed by aLCx-p and then aPCR-h. Comparison of the work flow of each
      assay revealed that although the aPCR-h demands the least specimen handling, the
      turnaround time of aLCx-p is the most favorable.

PMID- 9163450
TI  - Genetic characterization of multidrug-resistant Mycobacterium bovis strains from
      a hospital outbreak involving human immunodeficiency virus-positive patients.
AB  - Nineteen multidrug-resistant (MDR) Mycobacterium complex strains isolated in a
      nosocomial outbreak were characterized at the molecular level. The strains were
      microbiologically characterized as Mycobacterium bovis. The mpt40 sequence was
      not present in chromosomal DNA from these strains, supporting the fact that they
      were M. bovis. All of the isolates were resistant to isoniazid, rifampin,
      pyrazinamide, ethambutol, streptomycin, para-aminosalicylic acid, clarithromycin,
      cycloserine, ethionamide, ofloxacin, capreomycin, and amikacin. By performing the
      standardized IS6110 fingerprinting by restriction fragment length polymorphism
      (RFLP) analysis, we were able to differentiate two groups (groups A and B)
      containing two (16 isolates) and three (3 isolates) IS6110 copies, respectively.
      These strains were typed by spoligotyping, developed to distinguish M. bovis
      strains and also to distinguish them from M. tuberculosis strains (J. Kamerbeek
      et al., J. Clin. Microbiol. 35:907-914, 1997). All the strains were confirmed to
      be M. bovis. In addition, spoligotyping showed a difference in only 1 of 43
      spacers between RFLP groups A and B. The rpo beta region of several strains
      representative of each identified group was cloned and sequenced, and identical
      mutations (Ser-531 to Leu) responsible for the rifampin resistance phenotype were
      found. To our knowledge, this is the first characterization at the molecular
      level of an MDR M. bovis strain responsible for a nosocomial outbreak.

PMID- 9163451
TI  - Survival of Acinetobacter baumannii on dry surfaces.
AB  - Acinetobacter spp. have frequently been reported to be the causative agents of
      hospital outbreaks. The circumstances of some outbreaks demonstrated the long
      survival of Acinetobacter in a dry, inanimate environment. In laboratory
      experiments, we compared the abilities of five Acinetobacter baumannii strains,
      three Acinetobacter sp. strains from the American Type Culture Collection (ATCC),
      one Escherichia coli ATCC strain, and one Enterococcus faecium ATCC strain to
      survive under dry conditions. Bacterial solutions of the 10 strains were
      inoculated onto four different material samples (ceramic, polyvinyl chloride,
      rubber, and stainless steel) and stored under defined conditions. We investigated
      the bacterial counts of the material samples immediately after inoculation, after
      drying, and after 4 h, 1 day, and 1, 2, 4, 8, and 16 weeks of storage. A
      statistical model was used to distribute the 40 resulting curves among four types
      of survival curves. The type of survival curve was significantly associated with
      the bacterial strain but not with the material. The ability of the A. baumannii
      strains to survive under dry conditions varied greatly and correlated well with
      the source of the strain. Strains isolated from dry sources survived better than
      those isolated from wet sources. An outbreak strain that had caused hospital
      acquired respiratory tract infections survived better than the strains from wet
      sources, but not as well as strains from dry sources. Resistance to dry
      conditions may promote the transmissibility of a strain, but it is not sufficient
      to make a strain an epidemic one. However, in the case of an outbreak, sources of
      Acinetobacter must be expected in the dry environment.

PMID- 9163452
TI  - Comparison of biotyping, ribotyping, and pulsed-field gel electrophoresis for
      investigation of a common-source outbreak of Burkholderia pickettii bacteremia.
AB  - Over a 3-month period, six immunocompromised patients developed one or more
      episodes of Burkholderia pickettii bacteremia and/or catheter infection. Vials of
      a commercially available, "sterile" saline for injection which had been used for
      flushing the patients' indwelling intravenous devices were implicated as the
      common source of the organisms. No further cases were diagnosed once the use of
      this saline was discontinued. Twenty-six isolates, including 9 outbreak-related
      strains from case patients and contaminated saline as well as 17 control strains,
      were tested comparatively by biotyping, ribotyping with EcoRI and HindIII, and
      pulsed-field gel electrophoresis (PFGE) with SpeI. Macrorestriction analysis
      revealed nine PFGE groups and was more discriminating than ribotyping (seven
      ribotypes) and biotyping (two biovars). Among the outbreak-related isolates, one
      B. pickettii type was found by the three typing methods. Furthermore, PFGE was
      useful for subdividing ribotypes and for distinguishing isolates involved in the
      outbreak from all epidemiologically unrelated strains.

PMID- 9163453
TI  - Analysis of incidence of infection with enterotoxigenic Escherichia coli in a
      prospective cohort study of infant diarrhea in Nicaragua.
AB  - Diarrheal episodes with enterotoxigenic Escherichia coli (ETEC) were
      prospectively monitored during the first 2 years of life in a cohort of 235
      infants from Leon, Nicaragua. ETEC was an etiological finding in 38% (310 of 808)
      of diarrheal episodes and in 19% (277 of 1,472) of samples taken as asymptomatic
      controls at defined age intervals (P = <0.0001). The majority of diarrheal
      episodes (80%) occurred before 12 months of age. The major ETEC type was
      characterized by colonization factor CFA I and elaboration of both heat-labile
      enterotoxin and heat-stable enterotoxin (ST). The proportion of E. coli strains
      with CFA I was significantly higher in cases with diarrhea (P = 0.002). The
      second most prevalent type showed putative colonization factor PCFO166 and
      production of ST. The prevalence of PCFO166 was approximately 20%, higher than
      reported before. Children with a first CFA I episode contracted a second ETEC CFA
      I infection 24% of the time, compared with 46% for ETEC strains of any subtype.
      Most of the ETEC episodes were of moderate severity, and only 5% (15 of 310) were
      characterized as severe. In conclusion, our results give valuable information for
      the planning of intervention studies using ETEC vaccines.

PMID- 9163454
TI  - Determination of genotypes of Toxoplasma gondii strains isolated from patients
      with toxoplasmosis.
AB  - To determine the genotypes of Toxoplasma gondii strains associated with human
      toxoplasmosis, we developed a sensitive approach for typing parasites grown from
      clinical samples by short-term in vitro culture. A newly described nested PCR
      assay was capable of amplifying genomic DNA from as few as five parasites in the
      presence of host tissues. Typing was based on DNA polymorphisms at the SAG2
      locus, encoding tachyzoite surface antigen p22. Restriction fragment length
      polymorphisms in PCR-amplified SAG2 products were used to classify strains into
      one of the three major lineages of T. gondii. This approach was successfully used
      to determine the genotypes of 68 of 72 samples that had been previously isolated
      from patients with congenital, cerebral, and disseminated toxoplasmosis. Type II
      strains of T. gondii were found in a majority of the samples, accounting for 55
      (81%) of the 68 toxoplasmosis cases. In contrast, type I and III strains were
      found in only 7 (10%) and 6 (9%) of the 68 cases, respectively. The results of
      this study support the previous finding that type II strains are most often
      associated with human toxoplasmosis. Nested PCR analysis at the SAG2 locus
      provides rapid assignment of T. gondii to a specific genotype that should be
      useful in analyzing a variety of clinical samples.

PMID- 9163455
TI  - Contribution of a typing method based on IS256 probing of SmaI-digested cellular
      DNA to discrimination of European phage type 77 methicillin-resistant
      Staphylococcus aureus strains.
AB  - The incidence of infections with phage type 77 methicillin-resistant
      Staphylococcus aureus (MRSA) strains increased in France in 1987. These strains
      are widespread in numerous European hospitals. The SmaI restriction profiles of
      total DNA extracted from 74 phage type 77 MRSA strains isolated from 1987 to 1994
      in 10 hospitals in eight European cities (in France, Belgium, and Spain) were
      analyzed. Hybridization with a probe containing a 468-bp DNA fragment from within
      the transposase gene of the insertion sequence IS256 was also examined. Forty
      three SmaI profiles were detected. Twenty major genotypes were identified, and
      each genotype contained strains with the same profile or profiles which differed
      by no more than three bands. Strains isolated in different countries and at
      several-year intervals were often grouped within the same genotype. A larger
      number of genotypes could be discriminated by analysis of the patterns of
      hybridization with the IS256 probe. SmaI restriction fragments with the same
      apparent electrophoretic mobility could, in some cases, be distinguished by the
      presence or the absence of nucleotide sequences hybridizing with IS256. The
      strains that grouped within the same genotype after hybridization with IS256 were
      mostly those isolated in the same hospital and at less than 12-month intervals.
      Consequently, the IS256 probe that we used improved restriction profile analysis
      for discrimination between the intrahospital, outbreak-related phage type 77 MRSA
      strains and the endemic strains disseminated in various cities and countries.

PMID- 9163456
TI  - A simple method for determining metronidazole resistance of Helicobacter pylori.
AB  - The reliability of methods for determination of Helicobacter pylori resistance to
      metronidazole has been found to depend upon the incubation time. Because the disk
      diffusion method is more vulnerable than other methods to prolonged incubation,
      this method has not been recommended for H. pylori. However, because media
      designed for rapid growth of H. pylori have been introduced, the time has come to
      look at the clinical usefulness of this inexpensive and simple method again. The
      correlation of readings obtained with the E test (AB Biodisk, Solna, Sweden) and
      Rosco's (Taastrup, Denmark) disk diffusion method for in vitro metronidazole
      resistance determination for H. pylori with a short incubation time (24 to 31 h)
      was studied. Plates which could not be read after 24 to 31 h were reincubated for
      another night. Fifty-seven consecutive clinical strains were tested. Because the
      rate of regrowth of H. pylori depends upon the age of the colonies inoculated,
      the reproducibility of resistance test results for young colonies versus old
      colonies was also studied. Resistance plates could be read after 24 to 31 h of
      incubation for 28 of 29 strains when the inoculum consisted of young colonies (3
      to 4 days old). For these 29 strains, a high correlation (r = -0.937) was found
      between results obtained with the E test and those obtained with the disk
      diffusion test. A poorer correlation was found for old colonies (> or = 5 days
      old) (r = -0.742), which required a prolonged incubation for 8 of 23 strains. In
      conclusion, short incubation was successfully applied with young colonies.
      Results obtained with the simple and inexpensive disk diffusion method correlated
      well with those obtained with the E test.

PMID- 9163457
TI  - Etiological agents of infectious diarrhea: implications for requests for
      microbial culture.
AB  - Gastrointestinal infections remain a frequent disease worldwide. In order to
      increase our knowledge of the epidemiology for our patient population, we
      retrospectively analyzed the results obtained for stool samples received at the
      clinical microbiology laboratory of the University Hospital of Geneva during a 4
      year period. A total of 13,965 specimens from 7,124 patients (1.96 specimens per
      patient) were cultured, yielding 369 (2.6%) Salmonella spp., 408 (2.9%)
      Campylobacter spp., and 79 (0.6%) Shigella spp. The cumulative positivity rate of
      6.1% decreased to 2.7% when patients received antimicrobial agents (P < 0.001).
      The positivity rate for 5,912 specimens obtained from patients hospitalized for <
      or = 3 days was 12.6%, whereas it dropped to 1.4% for patients hospitalized for >
      3 days (P < 0.001). Of 3,837 stool samples originating from pediatric patients,
      8.8% were positive, and 5.1% of 10,128 samples from adults were positive (P <
      0.001). The cytotoxin of Clostridium difficile was detected in 379 of 3,723
      samples analyzed (10.2%), and rotaviruses were detected in 190 of 1,601 samples
      (11.9%). We recommend that the use of cultures for enteric bacterial pathogens be
      restricted to patients hospitalized for < or = 3 days, with the exceptions of
      follow-up samples, specimens from immunocompromised patients, and patients whose
      first sample was culture negative or in the rare event of nosocomial food-borne
      outbreaks. For patients under antimicrobial therapy, testing for cytotoxin of C.
      difficile should primarily be requested; this analysis should also be accepted
      for samples from patients not receiving antimicrobial agents at the time of
      specimen collection. By applying these restrictions, we could have saved at least
      $5,000 annually.

PMID- 9163458
TI  - Interpretation criteria for standardized Western blots for three European species
      of Borrelia burgdorferi sensu lato.
AB  - Western blots (WBs; immunoblots) are a widely used tool for the serodiagnosis of
      Lyme borreliosis, but so far, no defined criteria for performance, analysis, and
      interpretation have been established in Europe. For the current study WBs were
      produced with strains PKa2 (Borrelia burgdorferi sensu stricto), PKo (Borrelia
      afzelii), and PBi (Borrelia garinii). To improve resolution we used gels of 17 cm
      in length. In a first step, 13 immunodominant proteins were identified with
      monoclonal antibodies. Then, the apparent molecular masses of all visually
      distinguishable bands were determined densitometrically. Approximately 40 bands
      of between 14 and 100 kDa were differentiated for each strain. From a study with
      330 serum samples (from 189 patients with Lyme borreliosis and 141 controls), all
      observed bands were documented. To establish criteria for a positive WB result,
      the discriminating ability of a series of band combinations (interpretation
      rules) were evaluated separately for each strain (for immunoglobulin G [IgG] WB,
      > 40 combinations; for IgM WB, > 15 combinations). The following interpretation
      criteria resulting in specificities of greater than 96% were recommended: for IgG
      WB, at least one band of p83/100, p58, p56, OspC, p21, and p17a for PKa2; at
      least two bands of p83/100, p58, p43, p39, p30, OspC, p21, p17, and p14 for PKo;
      and at least one band of p83/100, p39, OspC, p21, and p17b for PBi; for IgM WB,
      at least one band of p39, OspC, and p17a or a strong p41 band for PKa2; at least
      one band of p39, OspC, and p17 or a strong p41 band for PKo; and at least one
      band of p39 and OspC or a strong p41 band for PBi. The overall sensitivity was
      the highest for PKo WB, followed by PBi and PKa2 WB, in decreasing order.
      Standardization of WB assays is necessary for comparison of results from
      different laboratories.

PMID- 9163459
TI  - Usefulness of PCR for diagnosis of Pneumocystis carinii pneumonia in different
      patient groups.
AB  - Pneumocystis carinii pneumonia (PCP) is one of the most predominant opportunistic
      infectious diseases in patients with AIDS. Nested PCR has been described as a
      sensitive and specific tool for detecting P. carinii DNA in clinical specimens.
      Little is known about the correlation of positive PCR results and clinical
      evidence of PCP in patients with different forms of immunosuppression. One
      hundred and thirty-six sputum samples, 26 tracheal-bronchial aspirate samples, 35
      bronchoalveolar lavage samples, and 11 lung biopsy samples from (i) human
      immunodeficiency virus (HIV)-infected patients with AIDS, (ii) immunocompromised
      patients with leukemia or lymphoma, and (iii) immunocompetent control patients
      were investigated by a nested PCR amplifying DNA from the mitochondrial large
      subunit of P. carinii. All patients suffered from acute episodes of respiratory
      disease. The resulting data were correlated with clinical evidence of PCP. A high
      degree of association of positive P. carinii PCR results and clinical evidence of
      PCP in HIV-infected patients with AIDS was found. When calculated for
      bronchoalveolar lavage and lung biopsy samples, the positive and the negative
      predictive values of P. carinii PCR for PCP diagnosis in HIV-infected patients
      with AIDS were 1 and the specificity and the sensitivity were 100%. In contrast,
      in the group of patients with leukemia or lymphoma, the positive predictive value
      of the nested PCR for these materials was found to be as low as 0.09, the
      negative predictive value was 0.73, the specificity was 44.4%, and the
      sensitivity was 25.0%. No P. carinii DNA could be detected in specimens from
      immunocompetent patients. In summary, in contrast to patients with leukemia and
      lymphoma, nested PCR seems to be a sensitive and specific tool for PCP diagnosis
      in HIV-infected patients with AIDS.

PMID- 9163460
TI  - Diagnosis of toxoplasmosis by joint detection of immunoglobulin A and
      immunoglobulin M.
AB  - An indirect immunofluorescence test with total anti-human immunoglobulin
      conjugate (IgG,A,M-IIF) can be used for joint detection of immunoglobulin A (IgA)
      and IgM antibodies, provided serum IgG is previously absorbed with anti-human
      IgG. To determine the validity of the IgG,A,M-IIF assay with absorbed sera, the
      results obtained were compared with those obtained by methods routinely used for
      the detection of acute-phase markers, IgA and IgM IIF and enzyme immunoassay.
      Accordingly, 114 serum samples were selected from patients showing titers of > or
      = 1:1,024 by IgG,A,M-IIF. (i) In 90 of the samples, neither IgA nor IgM was
      detected by any of the methods employed; (ii) the remaining 24 samples showed IgA
      and/or IgM. In all cases, the IgG,A,M-IIF assay with absorbed sera was positive.
      These comparative data support the use of IgG,A,M-IIF, performed with absorbed
      and unabsorbed sera simultaneously, for determining the presence of specific IgG,
      IgA, and IgM by employing a single technique (IIF), one conjugate (anti-IgG,A,M),
      and only one sample (with and without previous absorption), thus providing a
      useful initial tool for the diagnosis of toxoplasmosis.

PMID- 9163461
TI  - Rapid identification of Candida species in blood cultures by a clinically useful
      PCR method.
AB  - Widespread use of fluconazole for the prophylaxis and treatment of candidiasis
      has led to a reduction in the number of cases of candidemia caused by Candida
      albicans but has also resulted in the emergence of candidemias caused by innately
      fluconazole-resistant, non-C. albicans Candida species. Given the fulminant and
      rapidly fatal outcome of acute disseminated candidiasis, rapid identification of
      newly emerging Candida species in blood culture is critical for the
      implementation of appropriately targeted antifungal drug therapy. Therefore, we
      used a PCR-based assay to rapidly identify Candida species from positive blood
      culture bottles. This assay used fungus-specific, universal primers for DNA
      amplification and species-specific probes to identify C. albicans, C. krusei, C.
      parapsilosis, C. tropicalis, or C. glabrata amplicons. It also used a simpler and
      more rapid (1.5-h) sample preparation technique than those described previously
      and used detergent, heat, and mechanical breakage to recover Candida species DNA
      from blood cultures. A simple and rapid (3.5-h) enzyme immunosorbent assay (EIA)
      based format was then used for amplicon detection. One hundred fifty blood
      culture bottles, including 73 positive blood culture bottle sets (aerobic and
      anaerobic) from 31 patients with candidemia, were tested. The combined PCR and
      EIA methods (PCR-EIA) correctly identified all Candida species in 73 blood
      culture bottle sets, including bottles containing bacteria coisolated with yeasts
      and 3 cultures of samples from patients with mixed candidemias originally
      identified as single-species infections by routine phenotypic identification
      methods. Species identification time was reduced from a mean of 3.5 days by
      routine phenotypic methods to 7 h by the PCR-EIA method. No false-positive
      results were obtained for patients with bacteremias (n = 18), artificially
      produced non-Candida fungemias (n = 3), or bottles with no growth (n = 20).
      Analytical sensitivity was 1 cell per 2-microl sample. This method is simpler and
      more rapid than previously described molecular identification methods, can
      identify all five of the most medically important Candida species, and has the
      potential to be automated for use in the clinical microbiology laboratory.

PMID- 9163462
TI  - Rapid detection of oxacillin-resistant Staphylococcus aureus in blood cultures by
      an impedance method.
AB  - The feasibility of using an impedance method for direct detection of oxacillin
      resistant Staphylococcus aureus (ORSA) in blood cultures was evaluated. An
      aliquot (0.1 ml) of the positive blood culture, which showed growth of gram
      positive cocci and demonstrated thermonuclease activity, was inoculated into the
      module well of a Bactometer incubator (bioMerieux Vitek, Hazelwood, Mo.)
      containing 0.6 ml of Mueller-Hinton agar supplemented with oxacillin (2
      microg/ml). The modules were incubated at 37 degrees C, and the change in
      impedance in each well was continuously monitored by the instrument at 6-min
      intervals for 24 h. ORSA strains from blood cultures could multiply in the
      oxacillin-containing medium, and a time point (detection time [DT]) at which an
      accelerating change of impedance occurred in the medium was obtained, with an
      average of 5.5 h. The growth of oxacillin-sensitive S. aureus (OSSA) strains was
      largely inhibited, and no DT was obtained for these strains within an incubation
      period of 24 h. For 96 positive blood cultures (38 ORSA and 58 OSSA) tested, 36
      and 57 were found to be oxacillin resistant and oxacillin sensitive,
      respectively, by the impedance method. The impedance method had a sensitivity and
      specificity of 94.7 and 98.3%, respectively, for the detection of ORSA and had an
      agreement of 96.9% with the disc diffusion method. Comparable results were
      obtained by the testing of 235 clinical stock cultures of S. aureus (149 ORSA and
      86 OSSA). The impedance test is simple for detecting ORSA in blood cultures and
      may allow proper antimicrobial treatment almost 36 h before the results of the
      conventional culture methods are available.

PMID- 9163463
TI  - Prevalence of granulocytic Ehrlichia infection among white-tailed deer in
      Wisconsin.
AB  - Human granulocytic ehrlichiosis (HGE) is caused by an agent that is nearly
      indistinguishable from the veterinary pathogens Ehrlichia equi and Ehrlichia
      phagocytophila. The deer tick, Ixodes scapularis, is a vector of the HGE agent,
      and the white-tailed deer is the primary host for adult Ixodes ticks. We assessed
      the distribution of granulocytic Ehrlichia infection among deer living within
      (Wisconsin) and outside (western and southern Iowa) the geographic range of L.
      scapularis. Whole-blood samples were tested for HGE 16S ribosomal DNA (rDNA) by
      PCR, and E. equi antibody was detected by indirect immunofluorescence assay
      (IFA). Antibody titers of > or = 1:64 were defined as positive, and all positive
      samples were retested with a second lot of substrate antigen. E. equi antibody
      was present in 14 (8%) of 187 Wisconsin deer and 0 of 60 Iowa specimens (rate
      ratio undefined; P = 0.025). An additional 30 serum samples from Wisconsin deer
      were excluded because IFA results were discrepant between substrate lots. The
      reciprocal antibody titers ranged from 64 to 512 (geometric mean, 141) for
      positive samples. PCR results were positive for 27 (15%) of 181 Wisconsin deer.
      The prevalence of infection in northwestern Wisconsin deer was not significantly
      different from that in central Wisconsin deer, as determined by IFA and PCR. In
      two samples that were sequenced, the 16S rDNA was nearly identical to that of the
      granulocytic Ehrlichia species but distinct from that of Anaplasma marginale. The
      DNA sequences of the samples differed from the published sequences for E. equi,
      E. phagocytophila, and the HGE agent by 1 or 2 nucleotides (> or = 99.1%
      homology) at phylogenetically informative sites. Granulocytic Ehrlichia organisms
      in deer are widely distributed within the geographic range of L. scapularis in
      Wisconsin. Deer may serve as useful sentinels for areas where HGE transmission to
      humans may occur.

PMID- 9163464
TI  - Clinical comparison of BACTEC 9240 plus aerobic/F resin bottles and the isolator
      aerobic culture system for detection of bloodstream infections.
AB  - The Plus Aerobic/F resin bottle of the BACTEC 9240 automated blood culture system
      (Becton Dickinson Diagnostic Instrument Systems, Sparks, Md.) was compared with
      aerobic culture of the Isolator system (Wampole Laboratories, Cranbury, N.J.) for
      the detection of bloodstream microorganisms from 6,145 blood cultures collected
      from adult patients with suspected septicemia. The BACTEC resin bottles were
      incubated for 7 days, and the sediment from the Isolator tube was inoculated to
      sheep blood and chocolate agars which were incubated for 72 h and to inhibitory
      mold, brain heart infusion, and Sabouraud agars which were incubated for 21 days.
      A total of 622 microorganisms were recovered from 583 blood cultures. The BACTEC
      resin bottle recovered statistically significantly more pathogens overall than
      the Isolator system (P = 0.0006). When individual pathogens isolated from either
      system for a 7-day study period were assessed, it was determined that the BACTEC
      resin bottle detected statistically significantly more isolates of Staphylococcus
      aureus (P = 0.0113) and coagulase-negative Staphylococcus spp. (P = 0.0029) than
      the Isolator system. The BACTEC resin bottle also detected statistically
      significantly more bloodstream infections (septic episodes) caused by coagulase
      negative Staphylococcus spp. (P = 0.0146). The Isolator system recovered
      statistically significantly more contaminants overall (P < 0.0001), and among
      this group of microorganisms, recovered statistically significantly more Bacillus
      spp. (P < 0.0001), coagulase-negative Staphylococcus spp. (P < 0.0001), and
      viridans group Streptococcus spp. (P = 0.0156). The Isolator system detected
      statistically significantly more isolates of Histoplasma capsulatum (P = 0.004),
      but all of these isolates were detected at > or = 7 days of incubation of fungal
      plates, i.e., after the system to system comparison study period (7 days). In
      blood culture sets which produced growth of the same pathogen in both systems,
      there was a statistically significant difference in median time to detection for
      all pathogens combined favoring the BACTEC resin bottle over the Isolator tube (P
      < 0.05). When assessing individual microorganisms, the median times for detection
      of S. aureus, Enterococcus spp., and Pseudomonas spp. were all statistically
      significantly less for the BACTEC system (P < 0.05). The BACTEC instrument had 79
      (1.3%) false positive signals. The BACTEC system required less processing time
      than the Isolator system and eliminates the hands-on time for detection of
      positive cultures required with the Isolator system.

PMID- 9163465
TI  - Effects of incubation time and buffer concentration on in vitro activities of
      antifungal agents against Candida albicans.
AB  - Nine selected isolates of Candida albicans were tested for their susceptibilities
      to amphotericin B and fluconazole by using three methods to assess the effect of
      incubation time and buffer concentration. By using a microdilution method with
      0.0165 M 3-(N-morpholino)propanesulfonic acid (MOPS) and a 24-h incubation time,
      all of the isolates were found to be susceptible to amphotericin B and
      fluconazole. After 48 h of incubation, all isolates were still susceptible to
      amphotericin B. Seven of the nine isolates were resistant to fluconazole, and for
      the remaining two isolates, MICs increased by fourfold or more but the isolates
      remained susceptible (MIC, < or = 10 microg/ml). The nine isolates, along with
      three control strains, were further tested against amphotericin B and fluconazole
      by a standard broth macrodilution method with both 0.165 and 0.0165 M MOPS. The
      susceptibility results for fluconazole by the broth macrodilution method with the
      lower MOPS concentration correlated with the results of the 24-h broth
      microdilution method for determination of susceptibility or resistance in eight
      of nine tests and with the results of the 48 h broth microdilution method in
      three of nine tests. The results of the broth macrodilution method with the
      standard MOPS concentration did not correlate with any of the results obtained by
      the 24-h broth microdilution but correlated with results of seven of nine tests
      by the 48-h broth microdilution method. All nine test strains appeared to be
      susceptible when they were examined by a flow cytometric method. For clinical
      yeast susceptibility testing in microdilution panels, the 0.0165 M MOPS
      concentration combined with 24 h of incubation appeared to be the method of
      choice. The lower MOPS concentration may also be a useful modification to the
      tentative broth macrodilution method of the National Committee for Clinical
      Laboratory Standards. Use of the higher buffer concentration or longer incubation
      time may lead to false in vitro resistance for agents like fluconazole.

PMID- 9163466
TI  - Detection of Mycobacterium tuberculosis directly from sputum by using a prototype
      automated Q-beta replicase assay.
AB  - We have adapted an assay for the direct detection of Mycobacterium tuberculosis
      using a prototype automated instrument platform in which probes are amplified
      with Q-beta replicase. The assay was based on amplification of specific detector
      probe following four cycles of background reduction (reversible target capture)
      in a closed disposable pack. The assay signal was the time required for
      fluorescence to exceed background levels (response time [RT]). RT was inversely
      related to the number of M. tuberculosis rRNA target molecules in the sample.
      Equivalent signals and noises were observed in assays containing either sputum or
      buffer. All mock samples containing > or = 10 CFU of M. tuberculosis responded in
      the assay (average RT, 13.91 min), while most (83%) samples containing as many as
      10(7) CFU of Mycobacterium avium gave no response during a 25-min amplification
      reaction. The samples containing M. avium which did respond had an average RT of
      17.04 min. Seventy-five percent (167 of 223) of samples containing no target gave
      no responses; the remaining 25% had an average RT of 15.53 min. Eighty-three
      frozen sputum samples were tested to develop a candidate cutoff RT for the assay
      prior to more extensive clinical testing. After resolution of discrepant results
      and with a 14-min RT cutoff, 30 of 38 M. tuberculosis-positive samples were
      positive by the assay; 1 of 45 negative samples responded within 14 min. Assay
      sensitivity, specificity, and positive and negatives predictive values in this
      pilot study were 79, 98, 97, and 85%, respectively.

PMID- 9163467
TI  - Performance of an automated Q-beta replicase amplification assay for
      Mycobacterium tuberculosis in a clinical trial.
AB  - We present data from a clinical trial study in which an automated version
      (Galileo) of a previously described Q-Beta replicase-amplified probe assay (J. S.
      Shah et al., J. Clin. Microbiol. 33:1435-1441, 1995) was used for the direct
      detection of Mycobacterium tuberculosis complex in sputum. The assay was designed
      to target specific regions of 23S rRNA found in M. tuberculosis, Mycobacterium
      bovis, Mycobacterium africanum, and Mycobacterium microti and had a sensitivity
      ranging from approximately <10 to 300 CFU. The assay was tested for cross
      hybridization by using large numbers (e.g., 10(5)to 10(10) CFU/assay) of 133
      other organisms commonly found in respiratory tract samples, including non-M.
      tuberculosis Mycobacterium spp., other bacteria, fungi, and viruses. All of these
      competitors tested negative by the assay. Automated assay results for 780
      respiratory tract samples (sputum or bronchoalveolar lavage specimens) collected
      and tested at three trial sites in the United States) were compared with the
      results of culture and acid-fast microscopy. Aliquots of conventionally digested
      and decontaminated sputum pellets were heated at 100 degrees C and mechanically
      disrupted prior to hybridization and background reduction, amplification, and
      detection in a closed disposable test pack. Pertinent elements of individual
      patient histories relating to tuberculosis exposure, previous active disease,
      antituberculosis therapy status, etc., were considered in the resolution of
      discrepant results for 48 (assay false-positive) samples. Seventy-one of 90
      (78.9%) culture-positive samples were positive when tested in the Galileo assay,
      while 7% of culture-negative samples were assay positive, corresponding to a
      sensitivity of 79% and a specificity of 93%. Following resolution of discrepant
      results by chart review, the sensitivity and specificity for the Q-Beta replicase
      amplification assay with the Galileo analyzer were 84 and 97%, respectively. A
      total of 69.2% of smear-negative (culture positive) samples were detected by the
      assay. Ten test packs at a time were automatically processed by the Galileo
      analyzer without operator intervention following loading of samples. The first
      result was reported in approximately 3 h, and the last result was available in
      6.5 h. To our knowledge, this is the first report of a clinical study with a
      fully automated amplification probe hybridization assay for the detection of
      pathogens directly from a clinical specimen.

PMID- 9163468
TI  - Multiplex PCR assay for immediate identification of the infecting species in
      patients with mycobacterial disease.
AB  - Rapid identification of infecting mycobacterial species enables appropriate
      medical care decisions to be made. Our aim was to demonstrate the clinical
      usefulness of the multiplex PCR assay, a test based on PCR, which permits direct
      identification of 12 mycobacterial species in clinical specimens. A total of 259
      specimens from 177 patients who had clinical symptoms of mycobacterial disease
      but for whom there were difficulties in diagnosis were tested. Specimens were
      analyzed within 48 h of receipt of the sample. Mycobacteria were identified in
      102 specimens; 66 specimens contained nontuberculous mycobacteria, and 36
      specimens contained Mycobacterium tuberculosis complex mycobacteria. The PCR
      assay identified the mycobacterial species in 43 (97.7%) of 44 microscopy- and
      culture-positive specimens and in 15 (93.8%) of 16 culture-positive, microscopy
      negative specimens. It also permitted species identification in infections caused
      by more than one mycobacterial species. For 56 (96.5%) of the 58 specimens from
      patients with infections caused by opportunistic mycobacteria, the organisms were
      identified with the PCR assay. The test was useful also for the identification of
      fastidious mycobacteria, e.g., M. genavense, and those that cannot be cultured,
      e.g., M. leprae. After resolution of discrepant results, the sensitivity of the
      PCR assay was 97.9%, the specificity was 96.9%, the positive predictive value was
      95.0%, and the negative predictive value was 98.7%. For culture these values were
      60.8, 100, 100, and 81.0%, respectively. Thus, the multiplex PCR assay enables
      prompt diagnosis when rapid identification of infecting mycobacteria is
      necessary.

PMID- 9163469
TI  - Relationship between adhesion to intestinal Caco-2 cells and multidrug resistance
      in Klebsiella pneumoniae clinical isolates.
AB  - Klebsiella pneumoniae is an opportunistic gram-negative pathogen involved in
      outbreaks of nosocomial infections in intensive care units. Strains are resistant
      to multiple antibiotics, and 15 to 30% of them are also resistant to the broad
      spectrum cephalosporins by the production of R plasmid-encoded extended-spectrum
      beta-lactamases. Because the gastrointestinal tracts of patients have been shown
      to be the reservoir for nosocomial strains of K. pneumoniae, we looked for a
      correlation between antibiotic resistance and adhesion of K. pneumoniae strains
      to intestinal cells. We investigated adhesion to the human intestinal epithelial
      Caco-2 cell line of 61 clinical K. pneumoniae strains isolated in hospitals in
      Clermont-Ferrand, France. None of the strains tested expressed the previously
      described adhesive factors CF29K and KPF-28. Adhesive properties were found for
      42.6% of the strains tested (26 strains). Just 7.7% (2 strains) of the 26 strains
      producing only the chromosomally encoded SHV-1 beta-lactamase adhered to the Caco
      2 cell line, whereas 68.5% (24 strains) of the 35 strains producing a plasmid
      encoded beta-lactamase were adherent. All the adherent strains, and even the two
      strains producing only the SHV-1 enzyme, harbored at least one self-transmissible
      R plasmid. At variance for CAZ-1/TEM-5 or CAZ-5/SHV-4 beta-lactamase-producing K.
      pneumoniae strains, curing and mating experiments demonstrated that the self
      transmissible R plasmids encoding the TEM-1, CTX-1/TEM-3, CAZ-2/TEM-8, CAZ-6/TEM
      24, or CAZ-7/TEM-16 beta-lactamase were not involved in the adhesion of K.
      pneumoniae strains to intestinal epithelial cells. Nevertheless, there was an
      association of multiple antibiotic resistance, including resistance to extended
      spectrum cephalosporins, and adhesive properties in K. pneumoniae clinical
      isolates.

PMID- 9163470
TI  - Detection and typing of herpes simplex viruses by using recombinant
      immunoglobulin fragments produced in bacteria.
AB  - Thirty-seven bacterial clones producing human recombinant monoclonal antibody Fab
      fragments (rFabs) reactive to herpes simplex virus (HSV) antigens were selected
      from a human combinatorial antibody library constructed in a phage-display vector
      by a panning procedure against an HSV lysate. Thirty-four of the HSV-specific
      rFabs were able to specifically recognize HSV-infected cells in indirect
      immunofluorescence (IF) assays; of these, 25 recognized cells infected by either
      HSV type 1 (HSV-1) or HSV-2, while 9 recognized only HSV-1-infected cells. One
      HSV type-common rFab (rFab H37) and one HSV-1-specific rFab (rFab H85) were
      further evaluated as reagents for viral detection and typing by IF staining in
      134 HSV-positive (72 HSV-1 and 62 HSV-2) viral cultures from clinical specimens.
      The results obtained with these two rFabs were fully consistent with those
      obtained with a commercial preparation of fluorescein-labeled anti-HSV type
      specific murine monoclonal antibodies. The detection sensitivity with the type
      common rFab in indirect IF assays was higher overall than that provided by the
      type-specific murine monoclonal antibodies. Preparations of rFabs suitable for IF
      staining can be easily and inexpensively obtained in a clinical microbiology
      laboratory from Escherichia coli cultures. Similar HSV-specific rFabs, therefore,
      could be advantageous for in vitro diagnostic purposes.

PMID- 9163471
TI  - An indirect immunofluorescence assay using a cell culture-derived antigen for
      detection of antibodies to the agent of human granulocytic ehrlichiosis.
AB  - An indirect immunofluorescence assay for the detection of human antibodies to the
      agent of human granulocytic ehrlichiosis (HGE) was developed and standardized.
      Antigen was prepared from a human promyelocytic leukemia cell line (HL-60)
      infected with a tick-derived isolate of the HGE agent (USG3). Suitable antigen
      presentation and preservation of cellular morphology were obtained when infected
      cells were applied and cultured on the slide, excess medium was removed, and
      cells were fixed with acetone. Use of a buffer containing bovine serum albumin
      and goat serum reduced background fluorescence, and use of an immunoglobulin G
      (gamma-specific) conjugate reduced nonspecific binding. The assay readily
      detected specific antibody from HGE patients and did not detect antibody from
      healthy individuals. No significant reactivity was noted in sera from patients
      with high titers of antibodies to other rickettsial species. We were able to
      identify antibodies reactive to USG3 antigen in samples from areas where HGE is
      endemic that had tested negative to other rickettsial agents. Animal sera
      reactive against Ehrlichia equi or Ehrlichia phagocytophila bound to the HGE
      antigen, indicating that the assay may be useful for veterinary use.
      Comparability between two different laboratories was assessed by using coded
      human sera exchanged between laboratories. Results from the two laboratories were
      similar, indicating that the assay can be easily integrated into use for routine
      testing for HGE. The assay was then compared to an assay using horse neutrophils
      infected with ehrlichiae. The two assays gave comparable results, indicating that
      the cell culture-derived antigen can be used for testing samples that have been
      previously tested with E. equi as an antigen. The new assay offers several
      advantages over other immunofluorescence methods that use animal-derived antigen
      and is suitable for use in testing for human antibodies to the HGE agent.

PMID- 9163472
TI  - Outbreak of amoxicillin-resistant Haemophilus influenzae type b: variable number
      of tandem repeats as novel molecular markers.
AB  - An outbreak caused by amoxicillin-resistant Haemophilus influenzae type b was
      noted among patients suffering from chronic obstructive pulmonary disease. Since
      infections were clustered in time and place, an ongoing outbreak was suspected.
      The spread of the strain and the course of the outbreak could be followed by
      random amplification of polymorphic DNA (RAPD) analysis of the different
      bacterial isolates. In addition, studies were aimed at the determination of
      length polymorphism in regions of repetitive DNA. By PCR-mediated amplification
      of variable number of tandem repeat regions (VNTRs), additional insight into the
      genome composition of the epidemic strain was gained. Our results show that VNTRs
      comprising repeat units that are 3, 5, or 6 nucleotides in length provided stable
      genetic markers that can be used for molecular typing of H. influenzae type b.
      VNTRs built from tetranucleotide units, however, appear to be hypervariable and
      not suited for epidemiological studies. The observed variability in this latter
      class of VNTRs might be reminiscent of the bacterium's capacity to deal with
      unfavorable host factors.

PMID- 9163473
TI  - Random amplification of polymorphic DNA reveals serotype-specific clonal clusters
      among enterotoxigenic Escherichia coli strains isolated from humans.
AB  - The genetic diversity of 47 enterotoxigenic Escherichia coli (ETEC) strains of
      serotypes O6:H16, O27:H7, O29:H21, O128ac:H12, and O153:H45, previously isolated
      from diarrheic patients in Brazil over a period of 15 years, was investigated by
      random amplification of polymorphic DNA (RAPD). Informative band arrays were
      obtained with three 10-mer primers with G+C contents of 50, 60, and 70%. Based on
      the combination of the band profiles generated by the three primers 22 RAPD types
      were detected, and 5 major clonal clusters, each one with at least 80% identical
      bands, were established. The clonal clusters corresponded to strains having the
      same serotype which, in most cases, also had the same virulence factors
      (colonization factors and toxin types) and outer membrane protein and
      lipopolysaccharide sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      profiles. The results suggested a correlation between phenotypic properties and
      genetic relatedness of ETEC isolates of human origin and indicated that a reduced
      number of clonally related strains are found in areas of ETEC endemicity in
      Brazil. Moreover, the RAPD technique revealed intraserotype-specific variations,
      undetectable by the combination of several phenotypic typing methods, among the
      ETEC strains analyzed. These results show that RAPD typing represents a useful
      tool for population genetics as well as for epidemiological studies of ETEC.

PMID- 9163474
TI  - Evaluation of nine immunoassay kits (enzyme immunoassay and direct fluorescence)
      for detection of Giardia lamblia and Cryptosporidium parvum in human fecal
      specimens.
AB  - It is well known that Giardia lamblia and Cryptosporidium parvum can cause severe
      symptoms in humans, particularly those who are immunologically compromised.
      Immunoassay procedures offer both increased sensitivity and specificity compared
      to conventional staining methods. These reagents are also helpful when screening
      large numbers of patients, particularly in an outbreak situation or when
      screening patients with minimal symptoms. The data obtained by using 9 diagnostic
      kits were compared: direct fluorescent-antibody assay (DFA) kits (TechLab
      Giardia/Crypto IF kit, TechLab Crypto IF kit, and Meridian Merifluor
      Cryptosporidium/Giardia) and enzyme immunoassay (EIA) kits (Alexon ProSpecT
      Giardia EZ Microplate Assay, Alexon ProSpecT Cryptosporidium Microplate Assay,
      Cambridge Giardia lamblia Antigen Microwell ELISA, Meridian Premier Giardia
      lamblia, Meridian Premier Cryptosporidium, TechLab Giardia CELISA, Trend Giardia
      lamblia EIA). The test with the Meridian Merifluor Cryptosporidium/Giardia kit
      was used as the reference method. In various combinations, 60 specimens positive
      for Giardia, 60 specimens positive for Cryptosporidium, 40 specimens positive for
      a Giardia-Cryptosporidium mix, and 50 negative fecal specimens were tested.
      Different species (nine protozoa, three coccidia, one microsporidium, five
      nematodes, three cestodes, and one trematode) were included in the negative
      specimens. The sensitivity of EIA for Giardia ranged from 94% (Alexon) to 99%
      (Trend and Cambridge); the specificity was 100% with all EIA kits tested. The
      sensitivity of EIA for Cryptosporidium ranged from 98% (Alexon) to 99% (Meridian
      Premier); specificities were 100%. All DFA results were in agreement, with 100%
      sensitivity and specificity; however, the TechLab reagents resulted in
      fluorescence intensity that was generally one level below that seen with the
      reagents used in the reference method. In addition to sensitivity and
      specificity, factors such as cost, simplicity, ease of interpretation of results
      (color, intensity of fluorescence), equipment, available personnel, and number of
      tests ordered are also important considerations prior to kit selection.

PMID- 9163475
TI  - Evaluation of a rapid enzyme immunoassay for diagnosis of hepatic amoebiasis.
AB  - We compared the capability of rapid enzyme immunoassay (EIA) to detect
      antiamoebic antibodies during hepatic amoebiasis with those of indirect
      hemagglutination and latex agglutination. EIA is simple to perform and rapid (20
      min) and does not require any special equipment (optical reading is sufficient).
      EIA of 143 sera (including 43 from patients with proven hepatic amoebic abscess,
      33 from patients with other hepatic disorders and/or parasitic infections, and 67
      from healthy individuals) yielded a specificity, a sensitivity, and positive and
      negative predictive values of 100, 93, 100, and 97.1, respectively. This test
      could thus be considered another valuable tool for the diagnosis of hepatic
      amoebiasis.

PMID- 9163476
TI  - Use of pulsed-field gel electrophoresis to investigate a pseudo-outbreak of
      Bacillus cereus in a pediatric unit.
AB  - Bacillus cereus is a well-known cause of food poisoning. It also causes rare
      systemic infections, usually in immunocompromised patients. Dissemination of this
      species in hospitals had been reported. Most of these episodes were pseudo
      outbreaks and were usually secondary to equipment or environmental contamination.
      We report here on the use of pulsed-field gel electrophoresis (PFGE) to analyze a
      pseudo-outbreak of B. cereus in a pediatric unit. Different restriction
      endonucleases had been tested, and SmaI was found to give the best result for
      PFGE. Among the 26 clinical isolates of B. cereus and the type strain of the
      species, 15 distinct PFGE patterns were distinguished. PFGE after DNA
      macrorestriction with SmaI could clearly differentiate between the
      epidemiologically related isolates and the unrelated isolates. Because the same
      epidemic strain of B. cereus was isolated from the settle plates which were
      exposed near the outlet of the ventilation system, the source of this pseudo
      outbreak was suspected to be the unit's air filtration system. This is one of the
      first reports of the application of PFGE to the study of B. cereus, and this
      method is useful for epidemiological investigation.

PMID- 9163477
TI  - Detection of Neisseria gonorrhoeae and Chlamydia trachomatis in genitourinary
      specimens from men and women by a coamplification PCR assay.
AB  - A coamplification PCR test for the direct detection of Neisseria gonorrhoeae and
      Chlamydia trachomatis in urethral and endocervical swabs and urine samples from
      men and women was compared to standard culture techniques. Processed specimens
      were amplified in single reaction tubes containing primers for both organisms,
      and PCR products were detected by a colorimetric microwell plate hybridization
      assay specific for each pathogen. Of 344 specimens from men, 45 (13.1%) urine
      specimens were PCR positive for C. trachomatis, 51 (14.8%) urethral swab
      specimens were PCR positive, and 29 urethral swab specimens (8.4%) were culture
      positive. After analysis of discrepancies, the resolved sensitivity and
      specificity of PCR for C. trachomatis were 96.2 and 99.3%, respectively, in
      urethral swab specimens, compared to 88.2 and 98.6% for urine specimens. Of the
      192 specimens from women, 28 (14.6%) urine specimens were PCR positive for C.
      trachomatis, 32 (16.7%) endocervical specimens were PCR positive, and 19 (9.9%)
      endocervical specimens were culture positive. After analysis of discrepancies,
      the resolved sensitivity and specificity of PCR for C. trachomatis for
      endocervical specimens were both 100% compared to 100 and 99.4%, respectively,
      for urine specimens from women. In men, 68 (19.8%) urine specimens were PCR
      positive for N. gonorrhoeae, 73 (21.2%) urethral swabs were PCR positive, and 59
      (17.2%) urethral swabs were culture positive. After analysis of discrepancies,
      the resolved sensitivity and specificity of PCR for N. gonorrhoeae were 97.3 and
      97.0%, respectively, for urethral specimens compared to 94.4 and 98.5% for urine
      specimens. In women, 18 (9.4%) urine specimens were PCR positive for N.
      gonorrhoeae, 23 (12.0%) were endocervical swab PCR positive, and 15 (7.8%)
      endocervical specimens were culture positive. After analysis of discrepancies,
      the resolved sensitivity and specificity of PCR for N. gonorrhoeae were 100 and
      99.4%, respectively, for endocervical specimens compared to 90.0 and 95.9% for
      female urine specimens. These results indicate that a multiplex PCR is highly
      sensitive for detecting both C. trachomatis and N. gonorrhoeae from a single
      urine or genital swab, providing a more cost-effective way of screening multiple
      pathogens.

PMID- 9163478
TI  - Optimal combination of media for primary isolation of Helicobacter pylori from
      gastric biopsy specimens.
AB  - The aim of the present study was to compare eight media, four nonselective and
      four selective media, to determine the best combination of media for the primary
      isolation of Helicobacter pylori. Over a period of 5 months, mucosal antral
      biopsy specimens were obtained from 222 consecutive dyspeptic patients undergoing
      endoscopy. Biopsy samples were plated in parallel on all eight media. Egg yolk
      emulsion agar (EYE), Skirrow's medium, Dent's medium, and modified Thayer-Martin
      medium were used as selective media; modified chocolate agar (MCHOC), Triptycase
      soy agar (TSA), brucella agar, and brain heart infusion agar were used as
      nonselective media. Overall, by using these eight media, H. pylori was recovered
      from biopsy specimens from 114 of 222 patients, yielding an isolation rate of
      51%. Comparison of all possible combinations of the eight media showed that the
      highest rate of isolation of H. pylori was 100% (114 of 114) with EYE-MCHOC,
      followed by 96.5% (110 of 114) when EYE-TSA was used. Conversely, it was found
      that none of the media used alone yielded a 100% rate of recovery (the maximum
      recovery rate was 95%, which was achieved with EYE). These results indicate that
      the association of EYE and MCHOC yielded the maximum recovery of H. pylori from
      gastric biopsy specimens. Therefore, the use of selective and nonselective media
      in parallel offers optimal recovery rates with only a slight increase in costs.

PMID- 9163479
TI  - Oligonucleotide (GTG)5 as an epidemiological tool in the study of nontuberculous
      mycobacteria.
AB  - Analysis of restriction fragment length polymorphisms in the genome of
      Mycobacterium tuberculosis (DNA fingerprinting) has proved to be a useful
      epidemiological tool in the study of tuberculosis within populations or
      communities. However, to date, no similar method has been developed to study the
      epidemiology of nontuberculous mycobacteria (NTM). In this communication, we
      report that a simple oligonucleotide repeat, (GTG)5, can be used to accurately
      genotype all species and strains of NTM tested. We suggest that this technology
      is an easily applied and accurate tool which can be used for the study of the
      epidemiology of NTM.

PMID- 9163480
TI  - Molecular characterization of two Bordetella bronchiseptica strains isolated from
      children with coughs.
AB  - During a surveillance program associated with the Italian clinical trial for the
      evaluation of new acellular pertussis vaccines, two bacterial isolates were
      obtained in cultures of samples from immunocompetent infants who had episodes of
      cough. Both clinical isolates were identified as Bordetella bronchiseptica by
      biochemical criteria, although both strains agglutinated with antisera specific
      for Bordetella parapertussis, suggesting that the strains exhibited some
      characteristics of both B. bronchiseptica and B. parapertussis. Both children
      from whom these strains were isolated exhibited an increase in serum antibody
      titer to pertussis toxin (PT), a protein that is produced by Bordetella pertussis
      but that is not thought to be produced by B. bronchiseptica. We therefore
      examined whether the clinical isolates were capable of producing PT. Neither
      strain produced PT under laboratory conditions, although both strains appeared to
      contain a portion of the ptx region that encodes the structural subunits of PT.
      In order to determine whether the ptx genes may encode functional proteins, we
      inserted an active promoter directly upstream of the ptx region of one of these
      strains. Biologically active PT was produced, suggesting that this strain
      contains the genetic information necessary to encode an active PT molecule.
      Sequence analysis of the ptx promoter region of both strains indicated that,
      while they shared homology with the B. bronchiseptica ATCC 4617 sequence, they
      contained certain sequence motifs that are characteristic of B. parapertussis and
      certain motifs that are characteristic of B. pertussis. Taken together, these
      findings suggest that variant strains of B. bronchiseptica exist and might be
      capable of causing significant illness in humans.

PMID- 9163481
TI  - Human disease in Europe caused by a granulocytic Ehrlichia species.
AB  - Human granulocytic ehrlichiosis (HGE) was recently described in North America. It
      is caused by an Ehrlichia species closely related to Ehrlichia phagocytophila and
      Ehrlichia equi, recognized to infect mostly ruminants and horses, respectively.
      The vector in North America is the tick Ixodes scapularis, which is also the
      vector of the Lyme disease agent, Borrelia burgdorferi. Previous serologic
      studies in patients with a diagnosis of Lyme borreliosis indicate that HGE may
      exist in Europe. We report the first documented case of HGE in Europe. The
      diagnosis was established by seroconversion to E. equi and the HGE agent and by
      PCR with sequence analysis of the gene encoding the HGE agent 16S rRNA.
      Interestingly, the patient presented with a self-limited but moderately severe
      illness. Thus, European physicians need to be aware that HGE exists in Europe and
      that the diagnosis should be considered in febrile patients with tick bites in
      areas where Lyme disease is endemic.

PMID- 9163483
TI  - Emergence and dissemination of a highly vancomycin-resistant vanA strain of
      Enterococcus faecium at a large teaching hospital.
AB  - We prospectively identified patients at the Massachusetts General Hospital from
      whom vancomycin-resistant enterococci (VRE) were isolated from a clinical
      specimen from 1 January 1991 through 31 December 1995. VRE strains were available
      from 139 (82%) of the 169 patients with clinical cases. Of these, 39 (28%) were
      identical or closely related by pulsed-field gel electrophoresis (i.e., VRE type
      A strain), including 38 (43%) of 89 VRE strains in 1995. By multivariate
      analysis, acquisition of the VRE type A strain was associated with receipt of
      clindamycin (odds ratio [OR] = 10.5), 15 or more days of hospitalization before
      the first isolation of VRE (OR = 2.9), and residence on one of the general
      medical floors (OR = 7.8). The VRE type A strain was a vanA strain of
      Enterococcus faecium and was highly resistant to all antimicrobial agents tested
      except chloramphenicol. These findings document the rapid dissemination of a
      highly resistant strain of E. faecium among patients and among other extant VRE
      strains at the Massachusetts General Hospital in 1995.

PMID- 9163482
TI  - Detection of human papillomavirus type 16 early-gene transcription by reverse
      transcription-PCR is associated with abnormal cervical cytology.
AB  - Human papillomavirus type 16 (HPV-16) is associated with abnormal Papanicolou
      smears, indicative of cervical intraepithelial neoplasia. HPV-16 is the most
      common genital HPV and is found in up to 40% of young women with normal cervical
      cytology. In order to investigate whether transcriptionally active HPV-16
      infection is associated with abnormal cervical smears, a reverse transcription
      nested PCR assay with primers from the E5 open reading frame was developed to
      detect all HPV-16 early-region mRNA (E-mRNA) transcripts. It was used to study
      HPV-16-infected women with normal and abnormal cervical cytologies to obtain
      evidence of active infection. Among HPV-16 DNA-positive women, HPV-16 E-mRNA was
      detected in 15 of 37 (40.5%) women with abnormal cervical cytology but in only 4
      of 35 (11.4%) women with normal cytology (P = 0.007). Thus, HPV-16 E-mRNA
      transcription is associated with abnormal cervical smears and may have value as a
      prognostic marker of progressive disease.

PMID- 9163484
TI  - Detection of hydatid antigen in urine by countercurrent immunoelectrophoresis.
AB  - Hydatid antigen was demonstrated for the first time in the urine of patients with
      hydatid disease by countercurrent immunoelectrophoresis (CIEP). The antigen was
      detected in the concentrated urine of 7 of 16 (43.75% positive) patients with
      surgically confirmed hydatid disease, 4 of 10 (40% positive) patients with
      ultrasound-proven hydatid disease (daughter cysts or prominent septation and
      hydatid sands demonstrated by ultrasound), and 8 of 14 (57.14% positive) patients
      with clinically diagnosed (presumptive) hydatid disease. No antigen was detected
      in the concentrated urine from 24 patients with parasitic diseases other than
      hydatid disease. However, antigen was detected in 2 (8% false positive) of 25
      concentrated urine samples collected from healthy control subjects (blood donors
      and students). These result suggest that the detection of hydatid antigen in the
      urine by CIEP is a simple, rapid, and noninvasive method of diagnosis of hydatid
      disease.

PMID- 9163485
TI  - Dot immunoperoxidase assay for detection of parvovirus B19 antigens in serum
      samples.
AB  - We describe a simple and rapid dot immunoperoxidase assay for the direct
      detection of parvovirus B19 capsid antigens in human sera. The assay was
      performed with serum specimens dotted onto nylon membranes. VP1 and VP2 B19
      antigens, which represent 4 and 96% of the capsid, respectively, were detected
      with a pool of monoclonal antibodies directed against the two proteins, and the
      complex was visualized by immunoperoxidase staining. The assay could be performed
      in about 4 h, and positive results were revealed at the end of the reaction as
      dark blue spots on the nylon membrane at the site of positive specimens. A total
      of 541 serum samples from different subjects and with different laboratory
      evaluations with regard to B19 infection were analyzed. The results obtained by
      the dot immunoperoxidase assay were compared with the results obtained for the
      presence of B19 DNA by dot blot hybridization and nested PCR. With optimized
      working conditions, the dot immunoperoxidase assay was able to detect the
      presence of B19 with a sensitivity comparable or slightly higher than that
      achieved by dot blot hybridization but less than that achieved by nested PCR.
      Since the level of sensitivity of the dot immunoperoxidase assay proved to be
      appropriate for the detection of acute B19 infection, and since the cost, time to
      a result, and versatility of the assay are important issues, from our evaluation,
      the dot immunoperoxidase assay described may be particularly suitable for large
      scale screening of samples and a good alternative to DNA detection methods in the
      routine laboratory evaluation of B19 infection.

PMID- 9163486
TI  - Cost-effectiveness of rapid diagnosis of viral respiratory tract infections in
      pediatric patients.
AB  - Rapid diagnosis of respiratory viral infections in children resulted in
      significantly reduced hospital stays, antibiotic use, and laboratory utilization
      compared with those of a matched group of patients from the previous year who
      were diagnosed by virus culture. We demonstrate that rapid diagnosis of
      respiratory infections in children is a cost-effective procedure.

PMID- 9163487
TI  - Investigation of a pseudo-outbreak of Nocardia asteroides infection by pulsed
      field gel electrophoresis and randomly amplified polymorphic DNA PCR.
AB  - Molecular strain typing by pulsed-field gel electrophoresis and by randomly
      amplified polymorphic DNA analysis was used to investigate a cluster of four
      Nocardia asteroides isolates associated with the BACTEC 460 TB system. An
      instrument motor drive misalignment resulted in inadequate needle sterilization
      and cross-contamination of BACTEC vials. This pseudo-outbreak illustrates the
      importance of proper BACTEC 460 needle sterilization and maintenance and confirms
      the usefulness of molecular typing methods for epidemiologic investigations.

PMID- 9163489
TI  - Detection of Pneumocystis carinii in respiratory specimens by PCR-solution
      hybridization enzyme-linked immunoassay.
AB  - By using a recently developed PCR-solution hybridization enzyme-linked assay (PCR
      SHELA), we investigated Pneumocystis carinii in bronchoalveolar lavage fluid
      samples and induced sputa of patients with pneumocystosis. In detecting P.
      carinii, PCR-SHELA proved more sensitive than immunofluorescence staining or a
      single PCR and significantly more diagnostically specific than a nested PCR. Our
      data suggest that PCR-SHELA could be used to detect P. carinii organisms in
      respiratory samples, particularly in patients with uncertain diagnoses.

PMID- 9163488
TI  - Rapid discrimination of Mycobacterium avium strains from AIDS patients by
      randomly amplified polymorphic DNA analysis.
AB  - A randomly amplified polymorphic DNA (RAPD) analysis was performed for the
      molecular typing of Mycobacterium avium strains. This method was applied to
      epidemiologically unrelated M. avium strains isolated from the blood of 10
      different AIDS patients and to strains that were considered epidemiologically
      related, as they had been isolated from the same patient but from different body
      locations (4 patients, 10 strains). Three oligonucleotide primers among the six
      tested were found to generate RAPD profiles with DNA from all M. avium strains
      and to successfully type them. This method for the typing of M. avium strains is
      rapid and easy to perform.

PMID- 9163491
TI  - Demonstration of vertical transmission of Streptococcus suis in swine by genomic
      fingerprinting.
AB  - Isolates of Streptococcus suis serotype 5 collected from three sows and nine of
      their pigs at birth were analyzed by genomic DNA fingerprinting. The cleavage
      patterns of DNA from S. suis isolated from the sows matched the cleavage patterns
      of DNA from S. suis isolated from their respective pigs.

PMID- 9163490
TI  - Rapid detection of Mycoplasma pneumoniae by an assay based on PCR and probe
      hybridization in a nonradioactive microwell plate format.
AB  - A new molecular assay, based on a rapid DNA extraction protocol, PCR, and
      hybridization to a specific probe in a nonradioactive microwell plate format was
      used to detect Mycoplasma pneumoniae in bronchoalveolar fluid specimens. The
      sensitivity of the assay was determined to be 10 to 100 organisms with M.
      pneumoniae reference strains. Specificity testing with different bacteria capable
      of producing pneumonia showed no cross-reactivity. In a prospective study,
      bronchoalveolar lavage fluids obtained from patients with pneumonia were
      investigated with the PCR assay and compared to culture. Twelve positive samples
      were detected with the PCR assay. Seven of them were subsequently confirmed by
      culture. All patients with positive PCR results seroconverted. Application of the
      PCR assay described may lead to safe and early diagnosis of M. pneumoniae in
      patients with pneumonia.

PMID- 9163492
TI  - A single-tube nested PCR for Pneumocystis carinii f. sp. hominis.
AB  - A single-tube nested PCR which amplifies the internal transcribed spacer (ITS)
      regions of the rRNA genes of human Pneumocystis carinii was developed. The outer
      primers for the first PCR, which anneal to the 18S and the 26S rRNA genes of P.
      carinii, were made to have a midpoint temperature (Tm) of 74 degrees C. The inner
      primers for the second PCR have a Tm of 56 to 58 degrees C and are specific for
      human P. carinii; they anneal to an area close to the beginning of ITS1 and the
      junction of ITS2 and the 26S rRNA genes. The reaction mixture contained 2.5 pmol
      of the first-PCR primers and 25 pmol of the second-PCR primers. The first PCR was
      performed at an annealing temperature of 68 degrees C, which did not allow the
      second-PCR primers to function. Since very small amounts (2.5 pmol) of the first
      PCR primers were used, they were exhausted when the first PCR was completed. The
      single-tube nested PCR did not amplify P. carinii isolated from rats, mice, or
      ferrets. All 10 bronchoalveolar lavage (BAL) specimens from patients with P.
      carinii pneumonia were positive, whereas all 10 BAL specimens from patients with
      other diseases or patients infected with several commonly found fungi were
      negative by PCR.

PMID- 9163494
TI  - Evaluation of the COBAS AMPLICOR MTB system.
AB  - A panel of 1,012 respiratory sediments was retrospectively tested by PCR
      amplification to detect Mycobacterium tuberculosis with the COBAS AMPLICOR MTB
      system. The sensitivities and specificities of COBAS and fluorescence microscopy
      compared to culture were 92.6 versus 95.6% and 99.6 versus 95.3%, respectively.
      Inhibition occurred in 48 (4.7%) specimens.

PMID- 9163493
TI  - Detection of human Betaherpesvirinae in saliva and urine from immunocompromised
      and immunocompetent subjects.
AB  - Human cytomegalovirus (HCMV) is a well-known opportunistic agent that reactivates
      in human immunodeficiency virus (HIV)-seropositive subjects. Human herpesvirus 6
      (HHV-6) and HHV-7 were discovered recently and, like HCMV, belong to the
      Betaherpesvirinae subfamily. We looked for the presence of HCMV, HHV-6, and HHV-7
      by PCR with saliva and urine samples from 125 HIV-seropositive patients at
      different stages of HIV infection and with saliva and urine samples from 29 HIV
      seronegative subjects. All three viruses were frequently detected in the saliva
      (overall rates of detection, 61, 43, and 63% for HCMV, HHV-6, and HHV-7,
      respectively) with no correlation with the stage of immune deficiency. In
      contrast, HCMV was detected in urine much more frequently than the two other
      herpesviruses (overall rates of detection, 37, 2, and 6.5% for HCMV, HHV-6, and
      HHV-7, respectively) and was associated with immune deficiency. This suggests
      that these three genetically related viruses differ from each other with regard
      to replication in the urinary tract.

PMID- 9163495
TI  - Serological diagnosis of bovine, caprine, and ovine mastitis caused by Listeria
      monocytogenes by using an enzyme-linked immunosorbent assay.
AB  - An enzyme-linked immunosorbent assay for detecting Listeria monocytogenes
      antibodies in bovine (n = 35), caprine (n = 27), and ovine (n = 30) milk samples
      was evaluated by comparison with bacteriological examination. Microtiter plates
      were coated with proteins obtained from culture supernatant, and antibodies were
      revealed with a monoclonal antibody able to react with the immunoglobulins
      belonging to the three animal species. The arithmetic mean optical density (OD)
      of milk samples infected with L. monocytogenes was above that of uninfected milk
      samples or milk samples infected with pathogens others than L. monocytogenes.
      With an OD threshold of 0.2 for goat and ewe milk samples, the sensitivity and
      specificity of the test were 100 and 88%, respectively. The choice of a different
      OD threshold (0.5) for cows allowed the discrimination of all of the infected
      cows and yielded no false positives, and both sensitivity and specificity were
      100%.

PMID- 9163496
TI  - Use of heteroduplex analysis to classify legionellae on the basis of 5S rRNA gene
      sequences.
AB  - Seventeen different species of Legionella, 12 serogroups of Legionella
      pneumophila, and 2 Legionella-like amoebal pathogens (LLAP1 and Sarcobium
      lyticum) were examined by heteroduplex analysis of PCR products of the 5S rRNA
      gene. Eight different banding patterns were identified, indicating that
      heteroduplex analysis of this gene can be used to classify these bacteria
      according to base substitutions between species. This classification may have
      future applications in clinical and epidemiological studies.

PMID- 9163497
TI  - Use of quantitative competitive PCR to measure Epstein-Barr virus genome load in
      the peripheral blood of pediatric transplant patients with lymphoproliferative
      disorders.
AB  - A quantitative competitive PCR (QC-PCR) assay for Epstein-Barr virus (EBV) has
      been developed to provide accurate measurement of EBV genome load in pediatric
      transplant recipients at risk for developing posttransplant lymphoproliferative
      disorder (PTLD). The assay quantifies between 8 and 5,000 copies of the EBV
      genome in 10(5) lymphocytes after a 30-cycle amplification reaction. For 14
      pediatric patients diagnosed with PTLD, the median EBV genome load was 4,000, and
      13 of the 14 patients had values of >500 copies per 10(5) lymphocytes. Only 3 of
      12 control transplant recipients not diagnosed with PTLD had detectable viral
      genome loads (median value, 40). This median was calculated by using the highest
      value obtained by PCR testing on each of these patients posttransplantation. PCR
      values of >500 copies per 10(5) lymphocytes appear to correlate with a diagnosis
      of PTLD. By a modified protocol, the EBV genome copy number in latently infected
      adults was estimated to be <0.1 copy per 10(5) lymphocytes.

PMID- 9163498
TI  - Endocarditis caused by nonhemolytic group B streptococcus.
AB  - We report a case of bacterial endocarditis caused by nonhemolytic group B
      streptococcus (GBS) in a 67-year-old man with no predisposing risk factors.
      Nonhemolytic GBS strains rarely cause illness and are usually detected in
      perinatal infections. We believe this to be the first reported case of
      endocarditis caused by a nonhemolytic strain of GBS.

PMID- 9163499
TI  - Validity of self-obtained vaginal specimens for diagnosis of trichomoniasis.
AB  - A comparison of self- and clinician-collected vaginal specimens for the diagnosis
      of trichomoniasis was conducted. The sensitivities of culture methods using self-
      and clinician-collected specimens were 84.6 and 88.5%, respectively. There was no
      significant difference between the sensitivities of culture methods using self-
      and clinician-collected vaginal specimens for the diagnosis of trichomoniasis.

PMID- 9163500
TI  - Fecal PCR assay for diagnosis of Helicobacter infection in laboratory rodents.
AB  - A fecal PCR assay for detection of Helicobacter infections in laboratory rodents
      was developed. DNA was isolated from murine fecal pellets, and a region of the
      16S rRNA gene conserved among murine Helicobacter species was amplified. The
      fecal PCR was sensitive and specific. This assay does not require euthanasia of
      rodents, which is especially important for valuable rodents, such as transgenic
      mice.

PMID- 9163501
TI  - A novel method for isolation of Chlamydia pneumoniae by treatment with trypsin or
      EDTA.
AB  - To establish a novel method for the efficient isolation of Chlamydia pneumoniae,
      experiments were performed to determine the effects of EDTA or trypsin treatment
      of C. pneumoniae on its adsorption and inclusion body formation. Treatment of C.
      pneumoniae with 0.1% trypsin or 1 mM EDTA significantly increased inclusion body
      forming activity from 8,000- to 10,000-fold higher than that of the control. C.
      pneumoniae was successfully isolated in cultured cells which were inoculated with
      clinical specimens after treatment with 0.1% trypsin.

PMID- 9163502
TI  - Comparison of radioimmunoassay and enzyme immunoassay kits for detection of
      Legionella pneumophila serogroup 1 antigen in both concentrated and
      nonconcentrated urine samples.
AB  - We evaluated a commercial enzyme immunoassay (EIA) kit for detection of
      Legionella pneumophila serogroup 1 soluble antigen by comparing it to
      radioimmunoassay (RIA), using both concentrated and nonconcentrated urine
      samples. The sensitivity of EIA was 67.4% in nonconcentrated urine samples and
      82.6% in concentrated urine samples. The sensitivity of RIA was 60.9% and 84.8%
      in nonconcentrated and concentrated urine samples, respectively. Our study
      indicates that the sensitivity and specificity of EIA are comparable to those of
      RIA, and that concentrating the antigen by selective ultrafiltration increases
      sensitivity for both EIA and RIA, with no significant decrease in specificity.

PMID- 9163503
TI  - Rapid identification of Actinobacillus actinomycetemcomitans, Haemophilus
      aphrophilus, and Haemophilus paraphrophilus by restriction enzyme analysis of PCR
      amplified 16S rRNA genes.
AB  - Restriction enzyme analysis of PCR-amplified 16S rRNA genes was used to
      distinguish among clinical isolates of Actinobacillus actinomycetemcomitans,
      Haemophilus aphrophilus, and Haemophilus paraphrophilus which were originally
      identified by conventional phenotypic methods. This PCR-based method is a
      reliable and rapid alternative to conventional methods for identification of
      these bacterial species.

PMID- 9163504
TI  - Rapid detection of Vibrio cholerae O139 Bengal from stool specimens by PCR.
AB  - In a previous study using pure bacterial cultures in a PCR assay, a primer pair
      corresponding to a unique chromosomal region of Vibrio cholerae O139 Bengal
      generated an amplicon from only V. cholerae O139 Bengal. PCR with the same primer
      pair was used to screen 180 diarrheal stool specimens. All the 67 V. cholerae
      O139 culture-positive stool specimens were positive by PCR, and the remaining
      specimens, which contained either other recognized enteric pathogens or no
      pathogens, were all negative by PCR.

PMID- 9163505
TI  - Development of a highly specific assay for rapid identification of pathogenic
      strains of Yersinia enterocolitica based on PCR amplification of the Yersinia
      heat-stable enterotoxin gene (yst).
AB  - The chromosomal gene yst, which encodes a heat-stable enterotoxin of Yersinia
      enterocolitica, is a useful diagnostic marker because it occurs only in invasive
      strains of this species. A homologous gene also occurs in some strains of
      Yersinia kristensenii. Sequence analysis of the yst genes from two different
      strains of Y. enterocolitica and from Y. kristensenii revealed a substantial
      number of mismatches at the 3' ends of the yst genes of the so-called American
      and European biotypes of Y. enterocolitica. Moreover, several mismatches and a
      deletion of 5 codons were found in the yst of Y. kristensenii. These findings
      were used to develop a PCR-based assay for yst of Y. enterocolitica which yielded
      a detectable product in as little as 50 min. The assay was 100% specific in terms
      of its ability to identify potentially pathogenic strains of Y. enterocolitica
      regardless of biotype or serotype. The PCR yielded an amplicon that was visible
      on agarose gel electrophoresis from as few as 100 CFU, or 10 CFU when the PCR was
      combined with dot blot hybridization with a digoxigenin-labeled oligonucleotide
      probe that corresponded to an internal sequence of yst. These results establish
      the value of the yst gene as a target for the identification of pathogenic
      bioserotypes of Y. enterocolitica and the usefulness of PCR for this purpose.

PMID- 9163507
TI  - Prevalence of the virulence-associated gene of Rhodococcus equi in isolates from
      infected foals.
AB  - The prevalence of the plasmid-encoded virulence-associated gene (vapA) of
      Rhodococcus equi, as determined by PCR, was found to be 98% in isolates from 154
      foals with pneumonia, confirming the strong association of vapA with virulence.
      The vapA genes from 60 representative isolates were compared by digestion with
      the restriction endonuclease HinfI, and no evidence of sequence variation was
      detected.

PMID- 9163506
TI  - Coli surface antigens associated with enterotoxigenic Escherichia coli strains
      isolated from persons with traveler's diarrhea in Asia.
AB  - Enterotoxigenic Escherichia coli (ETEC) strains were isolated from travelers or
      military personnel who developed diarrhea after visiting Nepal or who were
      deployed to Thailand, Indonesia, or the Philippines. ETEC isolates were examined
      for colonization factor antigen (CFA). CFAs were identified on 59% (40 of 68) of
      the isolates examined. The lack of a detectable CFA on 41% (28 of 68) of the
      isolates is of concern for the development of an effective ETEC vaccine.

PMID- 9163508
TI  - Coinfection with Tropheryma whippelii and a Whipple's disease-associated
      bacterial organism detected in a patient with central nervous system Whipple's
      disease.

PMID- 9163509
TI  - Amplification and restriction endonuclease digestion of a large fragment of genes
      coding for rRNA as a rapid method for discrimination of closely related
      pathogenic bacteria.

PMID- 9163510
TI  - Real time observation of binding of herpes simplex virus type 1 (HSV-1) to Vero
      cells and neutralization of HSV-1 by sulfonated human immunoglobulin.
AB  - A real time biomolecular interaction assay system involving an optical sensor was
      applied to the quantitative analysis of the binding of herpes simplex virus type
      1 (HSV-1) to Vero cells, and the neutralization antibody titer against this virus
      with a commercially available sulfonated human immunoglobulin preparation. The
      virus titers in a viral solution and the neutralizing antibody titer in the human
      immunoglobulin preparation could be successfully estimated in a short time with
      this system without any difficult cytopathic effect analysis of cultured cells.

PMID- 9163511
TI  - Three-dimensional structure of Escherichia coli branched-chain amino acid
      aminotransferase at 2.5 A resolution.
AB  - The X-ray crystallographic structure of the branched-chain amino acid
      aminotransferase from Escherichia coli was determined by means of isomorphous
      replacement using the selenomethionyl enzyme as one of the heavy atom
      derivatives. The enzyme is a homo hexamer with D3 symmetry, and the polypeptide
      chain of the subunit is folded into two domains (small and large domains). The
      coenzyme, pyridoxal 5'-phosphate, resides at the domain interface, its re-face
      facing toward the protein. The active site structure shows that the following
      sites can recognize branched-chain amino acids and glutamate as substrates: (1) a
      hydrophobic core formed by Phe36, Tyr164, Tyr31*, and Val109* for a branched
      chain; (2) Arg97 for an acidic side chain of glutamate; and (3) Tyr95 and two
      main chain NH groups of Thr257 and Ala258 for the alpha-carboxylate of
      substrates. Although the main chain conformation of the active site is homologous
      to that of D-amino acid aminotransferase, many of the active site residues are
      different between them.

PMID- 9163512
TI  - Release of a newly-identified cysteine protease, tetrain, from Tetrahymena into
      culture medium during the cell growth.
AB  - Protease activity in the culture medium of Tetrahymena pyriformis markedly
      increased during the growth of the ciliate. The protease activity in the culture
      medium was purified by sequential column chromatographies. The purified protease
      had an apparent molecular mass of 28 kDa. N-terminal amino acid sequencing
      analysis suggested that the protease is a mature form of cysteine protease.
      Requirements of free sulfhydryl groups for activity and sensitivity to N-tosyl-L
      phenylalanine chloromethyl ketone and Na-p-tosyl-L-lysine chloromethyl ketone
      also indicated that the protease is a member of the papain family of cysteine
      proteases. The protease was designated as tetrain. Immunoblotting analyses showed
      that tetrain was present in higher amount in the culture medium in the stationary
      phase than in the logarithmic phase. Tetrain has high activities at neutral to
      alkaline pH values. This suggests that tetrain has functional roles in the
      culture medium in the stationary phase, because the pH of the culture medium
      became alkaline with the progress of Tetrahymena growth.

PMID- 9163513
TI  - Temperature sensitivity of proteoliposomes reconstituted from a mixture of
      scallop and rabbit sarcoplasmic reticulum Ca2+-ATPases.
AB  - We reconstituted proteoliposomes by mixing scallop and rabbit sarcoplasmic
      reticulum, SR, at different protein weight ratios, and investigated the effects
      of temperature on their Ca2+-transport activity. When proteoliposomes containing
      scallop and rabbit SR at a protein ratio of 1:1 were pre-incubated in the
      presence of Ca2+ at 39 degrees C for 10 min, the Ca2+-transport activity was
      almost completely lost, whereas the activity of proteoliposomes containing rabbit
      SR alone decreased only slightly. Essentially the same results were obtained for
      proteoliposomes reconstituted with Ca2+-ATPases partially purified from scallop
      and rabbit SR. The susceptibility of the reconstituted proteoliposomes to heat
      inactivation increased with an increase in the protein weight ratio of scallop to
      rabbit SR, the maximum being approached at a ratio higher than 1. When the
      scallop SR was thermally treated before reconstitution, the resulting vesicles
      showed as high Ca2+-transport activity as that of control vesicles reconstituted
      from rabbit SR alone. The former vesicles were not inactivated on further
      treatment at high temperature. In contrast, when the scallop SR was heated in
      EGTA before reconstitution of vesicles with rabbit SR, the Ca2+-transport
      activity of the vesicles was strongly inhibited by subsequent treatment at high
      temperature in the presence of Ca2+. These results can be easily explained if we
      assume that Ca2+ transport by the reconstituted vesicles can be catalyzed through
      a dimeric interaction between the scallop and rabbit Ca2+-ATPases in the
      membrane. Pre-incubation of these vesicles at 39 degrees C for 10 min in the
      presence of Ca2+ may destroy the dimeric interaction due to denaturation of the
      scallop Ca2+-ATPase.

PMID- 9163514
TI  - Remarkable functional aspects of myoglobin induced by diazaheme prosthetic group.
AB  - The iron complex of beta,delta-diazamesoporphyrin III, a molecular hybrid of
      porphyrin and phthalocyanine, was incorporated into apomyoglobin to investigate
      novel biological aspects of myoglobin. The reconstituted ferric protein forms an
      internal hemichrome with the iron-bound distal histidine. The reduced ferrous
      protein has extraordinarily high affinities for O2 and CO. The ferrous myoglobin
      is capable of strong binding with pyridine, imidazole, cyanide, and azide, and
      reacts moderately with ammonia. The NO complex exhibited 5-coordinate to 6
      coordinate transition over 150 min. The instability of 5-coordinate NO heme is
      consistent with a high affinity of imidazole to the ferrous heme. The kinetic
      analyses of the ferrous derivatives suggest the importance of the pi orbitals in
      neutral ligands as well as the negative charges in anionic ligands. A high
      affinity of imidazole to ferrous diazaheme accounts for the internal hemochrome
      formation in ferrous myoglobin containing phthalocyanines.

PMID- 9163515
TI  - Identification and characterization of functional residues in a Na+/H+ antiporter
      (NhaA) from Escherichia coli by random mutagenesis.
AB  - Forty-one mutants were isolated by means of random PCR mutagenesis of the
      Escherichia coli Na+/H+ antiporter (nhaA), which could not support the growth of
      a nhaAnhaB mutant (HIT delta AB-) on plates containing 0.15 M LiCl (pH 7.5) or
      0.65 M NaCl (pH 8.0). Most of the mutants were sensitive to both NaCl and LiCl,
      or to LiCl alone. DNA sequencing revealed that twelve of the mutants had single
      amino acid substitutions. All the mutations, except for H225P, were of the
      conserved residues of NhaA homologues and located in the putative transmembrane
      helices. The Na+/H+ and Li+/H+ antiporter activities of the mutant NhaA were
      measured with everted membrane vesicles: eight of the mutants lost both
      antiporter activities completely under all pH conditions examined. Although both
      D133A and L138P retained low Li+/H+ antiporter activity, D133A lost Na+/H+
      antiporter activity, while L138P retained normal Na+/H+ antiporter activity at pH
      7.0 and 8.0. Interestingly, at pH 8.5, L138P no longer showed any Li+/H+
      antiporter activity. H225P retained relatively high antiporter activities,
      although their pH dependence was altered. These observations supported the
      previous indication that His-225 is part of the pH sensor [Gerchman, Y. et al.
      (1993) Proc. Natl. Acad. Sci. USA 90, 1212-1216]. L73R exhibited about 20% each
      of the activities only at pH 8.0, and showed a similar pH dependence to H225P in
      both Na+/H+ and Li+/H+ antiport. Therefore, in addition to His-225, Leu-73,
      and/or its vicinity may also contribute to the pH sensing.

PMID- 9163516
TI  - Structure of the ascidian, Halocynthia roretzi, troponin C gene.
AB  - Two distinct cDNAs encoding troponin C (TnC) isoforms were isolated from the
      ascidian, Halocynthia roretzi. One is expressed in adult body wall smooth muscle
      and heart muscle, and the other in larval striated muscle. The H. rorezti gene is
      composed of 7 exons separated by 6 introns, and Southern blot analysis showed
      that TnC is a single copy gene product. The two isoforms of TnC were derived
      through the alternative splicing of the third exon.

PMID- 9163517
TI  - Analysis of IFN-gamma-induced cell cycle arrest and cell death in hepatocytes.
AB  - The mechanism by which IFN-gamma induces cell cycle arrest and cell death in
      primary cultured hepatocytes was examined. The cell death exhibits apoptotic
      characters such as the appearance of apoptotic bodies and DNA fragmentation. IFN
      gamma induced cell cycle arrest at the initial stage, followed by cell death. A
      protein synthesis inhibitor, cycloheximide, significantly inhibited cell death,
      implying that IFN-gamma induces de novo proteins involved in the death of
      hepatocytes. One of the most important apoptosis-related proteins, p53, was
      induced by IFN-gamma in hepatocytes in a dose- and time-dependent manner.
      Northern blot analysis demonstrated that IFN-gamma enhanced p53 mRNA expression
      as well as p21(WAF1/Cip1/Sdi1) mRNA expression, which is mediated by the
      increased expression of the p53 protein. Interestingly, IFN-gamma also induced
      cell death in p53-deficient hepatocytes. The cell death occurred rather earlier
      in p53-deficient cells than in normal hepatocytes. However, the cell death was
      not accompanied by apoptotic bodies. Therefore, IFN-gamma-induced hepatocyte cell
      death is p53-independent, and p53 may contribute to the apoptotic characters. In
      conclusion, IFN-gamma is supposed to cause cell cycle arrest by inducing p53 and
      p21(WAF1/Cip1/Sdi1), and it was demonstrated that IFN-gamma induces p53
      independent cell death in primary cultured hepatocytes.

PMID- 9163519
TI  - Amino acid sequence and chemical modification of a novel alpha-neurotoxin (Oh-5)
      from king cobra (Ophiophagus hannah) venom.
AB  - A novel alpha-neurotoxin, Oh-5, was isolated from king cobra (Ophiophagus hannah)
      venom and purified by successive SP-Sephadex C-25 column chromatography and
      reversed-phase HPLC. The complete sequence of Oh-5 was determined by Edman
      degradation of peptide fragments generated by endopeptidases, i.e., trypsin,
      Saccharomyces aureus V8 protease and lysyl endopeptidase. This novel toxin
      comprises 72 amino acid residues with 10 cysteines. The sequence shows 89%
      sequence homology with Oh-4, and 60% with Toxins a and b from the same venom. The
      tyrosine, tryptophan, lysine and arginine residues in Oh-5 were modified with
      tetranitromethane (TNM), 2-nitrophenylsulfenyl (NPS) chloride, trinitrobenzene
      sulfonate (TNBS), and p-hydroxyphenylglyoxal (HPG), respectively. Modification of
      Tyr-4 or Trp-27 did not affect the lethal toxicity at all, while the Tyr-4 and 23
      nitrated derivative retained about 50% of the lethality of native toxin.
      Selective trinitrophenylation of Lys-51 or 69 resulted in a decrease in lethality
      by 29%, and 50% lethality was retained after modification of Lys-2, 51, and 69. A
      drastic decrease in lethality to 26% was observed when both Arg-35 and 37 were
      modified. The neurotoxicity was further decreased when Arg-9 was additionally
      modified. These results suggest that the aromatic residues, Tyr-4 and Trp-27, are
      not crucial for the neurotoxicity, whereas the cationic residues are involved in
      multipoint contact between the toxin molecule and the nicotinic acetylcholine
      receptor (nAChR). The residues Tyr-23 and Arg-35 and 37 in the central loop of Oh
      5 seem to contribute greatly to the neurotoxicity.

PMID- 9163518
TI  - Purification and characterization of a new ubiquitin C-terminal hydrolase (UCH-1)
      with isopeptidase activity from chick skeletal muscle.
AB  - We have previously shown that chick muscle extracts contain at least 10 different
      ubiquitin C-terminal hydrolases (UCHs). In the present studies, one of the
      enzymes, called UCH-1 was partially purified by conventional chromatographic
      procedures using (125)I-labeled ubiquitin-alphaNH-MHISPPEPESEEEEEHYC as a
      substrate. The purified enzyme behaved as a 35-kDa protein under both denaturing
      and nondenaturing conditions, suggesting that it consisted of a single
      polypeptide chain. It was maximally active at pHs between 8 and 9, but showed
      little or no activity at pH below 6 and above 11. Like other UCHs, its activity
      was strongly inhibited by sulfhydryl blocking reagents, such as iodoacetamide,
      and by ubiquitin-aldehyde. In addition to Ub-PESTc, UCH-1 hydrolyzed ubiquitin
      alphaNH-protein extensions, including ubiquitin-alphaNH-carboxyl extension
      protein of 80 amino acids, ubiquitin-alphaNH-dihydrofolate reductase, and poly
      His-tagged di-ubiquitin. This enzyme was also capable of generating free
      ubiquitin from mono-ubiquitin-epsilonNH-protein conjugates and from branched poly
      ubiquitin chains that are ligated to proteins through epsilon NH-isopeptide
      bonds. These results suggest that UCH-1 may play an important role in the
      generation of free ubiquitin from ubiquitin-ribosomal protein fusions and linear
      poly-ubiquitin, as well as in recycling of Ub molecules after degradation of poly
      ubiquitinated protein conjugates by the 26S proteasome.

PMID- 9163520
TI  - Effects of random mutagenesis in a putative substrate-binding domain of
      geranylgeranyl diphosphate synthase upon intermediate formation and substrate
      specificity.
AB  - Archaeal geranylgeranyl diphosphate (GGPP) synthase catalyzes the consecutive
      condensation of isopentenyl diphosphate (IPP) with allylic diphosphates to
      produce GGPP with significant amounts of intermediates. To obtain information
      about the amino acids involved in the condensation and the release of
      intermediates, we randomly mutagenized two proximal regions, I and II, of the
      Sulfolobus acidocaldarius GGPP synthase gene and created two degenerate
      libraries, I and II, respectively. Regions I and II correspond to amino acid
      residues 170-173 and 166-168, respectively. The prenyltransferase activities of
      about 200 clones were analyzed using the in vivo red-white system and the
      conventional in vitro assay. Although, in library I, no mutated enzymes that
      failed to catalyze the formation of GGPP were found, as assayed with the red
      white system, almost all the mutated enzymes exhibited weak GGPP synthesis
      activity, and many produced large amounts of intermediates. The formation of
      intermediates increased as the concentration of IPP was decreased or as the
      concentration of the allylic substrate was increased. These phenomena can be
      regarded as a reflection of the increased K(m) for IPP and the decreased affinity
      for products including intermediates. On the other hand, no mutants from library
      II showed such changes. These results suggest that the region from 170 to 173 is
      concerned in the recognition of both IPP and allylic diphosphates, and that the
      change in responsiveness to prenyl diphosphates causes a change in intermediate
      formation.

PMID- 9163521
TI  - Characterization of acetohexamide reductases purified from rabbit liver, kidney,
      and heart: structural requirements for substrates and inhibitors.
AB  - The structural requirements of acetohexamide reductases purified from rabbit
      liver, kidney, and heart for substrates and inhibitors were examined.
      Acetohexamide, an oral antidiabetic drug with a ketone group, and analogs of it
      with various alkyl groups instead of the cyclohexyl group were used as substrates
      for these three enzymes. The results obtained as to substrate specificity
      suggested that the nature of the substrate-binding region of the heart enzyme is
      markedly different from those of the substrate-binding regions of the liver and
      kidney enzymes. Tolbutamide, which has no ketone group within its chemical
      structure, strongly inhibited the heart enzyme, whereas it had little ability to
      inhibit the liver or kidney enzyme. The inhibition of the heart enzyme by
      tolbutamide was competitive with respect to acetohexamide and uncompetitive with
      respect to NADPH. Furthermore, tolbutamide analogs with n-pentyl and n-hexyl
      groups instead of the n-butyl group exhibited very pronounced inhibition of only
      the heart enzyme. Therefore, it is reasonable to postulate that the heart enzyme,
      unlike the liver and kidney ones, has a cleft of a strongly hydrophobic nature
      near its substrate-binding region, and that this hydrophobic cleft plays a
      critical role in the interaction of the heart enzyme with the cyclohexyl group of
      acetohexamide.

PMID- 9163522
TI  - Nucleotide sequence of the promoter region of chicken cytosolic
      phosphoenolpyruvate carboxykinase gene.
AB  - The nucleotide sequence of the promoter region and its flanking regions which
      span - 1855 to +2083 in the chicken cytosolic phosphoenolpyruvate carboxykinase
      gene was determined. The transcription initiation site was located at 119
      nucleotides downstream of the previously reported chicken kidney transcription
      initiation site of this gene. The nucleotide sequences of exons 1, 2, and 3 were
      highly homologous to the corresponding exons of the rat gene. Homology of the
      sequence - 1 to - 500 to that of rat gene was 52% and most of the hormone
      responsive sequences in rat gene, such as the glucocorticoid-responsive region,
      were not conserved in the chicken gene, in accord with the species-specific
      responsiveness to starvation. In contrast, in the region of - 1 to - 300, some
      sequence motifs conserved both in the chicken and rat genes were found at
      essentially the same positions in the promoters. Such sequence motifs included a
      cAMP-responsive element (CRE), a nuclear factor-1 (NF-1/CTF)-binding site, and a
      hepatocyte nuclear factor-1 (HNF-1)-binding site. Transient expression of the
      reporter luciferase gene ligated to the 3' end of this chicken sequence (-1855 to
      +7) was observed in a primary culture of chick hepatocytes when dibutyryl cyclic
      AMP was added to the culture medium.

PMID- 9163523
TI  - Comparison of the gene expression of aspartate beta-D-semialdehyde dehydrogenase
      at elevated hydrostatic pressure in deep-sea bacteria.
AB  - Aspartate beta-D-semialdehyde dehydrogenase genes (asd) were cloned and sequenced
      from a deep-sea-adapted strictly barophilic bacterium, Shewanella sp. strain
      DB6705, and a moderately barophilic bacterium, Shewanella sp. strain DSS12. The
      determined asd sequences of these two strains were very similar, and the identity
      of the deduced amino acids sequences was 96.2%. The 5'-ends of the asd mRNA from
      both strains were localized at corresponding sites by primer extension analysis,
      and two transcriptional starting points, which differed by only 1 base, were
      detected. In strain DB6705, a pressure-regulated transcript was mainly observed,
      whereas in strain DSS12, a pressure-tolerant transcript was observed together
      with the pressure-regulated transcript. Western-blotting analysis showed that the
      ASD protein was expressed under higher pressure conditions in DB6705, and under
      all pressure conditions tested in DSS12, as reflected in the primer extension
      results. Our findings suggest that asd expression controlled by pressure is one
      of the important mechanisms involved in the adaptation of microorganisms to the
      deep-sea environment.

PMID- 9163524
TI  - Inhibition of fructose-6-phosphate,2-kinase by N-bromoacetylethanolamine
      phosphate in vitro and in vivo.
AB  - Fructose-6-phosphate,2-kinase/fructose-2,6-bisphosphatase (Fru-6-P,2-kinase/Fru
      2,6-BPase), a bifunctional enzyme, catalyzes the synthesis and degradation of a
      potent activator, fructose-2,6-bisphosphate (Fru-2,6-P2), of phosphofructokinase,
      and has been postulated to be an important enzyme in the regulation of glycolysis
      in mammalian tissues. The purpose of this study was to determine whether or not N
      bromoacetylethanolamine phosphate (BrAcNHEtOP), a specific active site-directed
      inactivator of Fru-6-P,2-kinase, is useful for studies on the role of Fru-6-P,2
      kinase in the regulation of glycolysis in vivo. BrAcNHEtOP inactivated purified
      recombinant rat testis-type Fru-6-P,2-kinase as well as Fru-6-P,2-kinase in a rat
      liver extract, with half maximum inactivation concentrations of 2 and 15 mM,
      respectively, on 30 min incubation at 30 degrees C. The increases in Fru-6-P,2
      kinase activity and the Fru-2,6-P2 concentration in livers, prepared from fasted
      rats, induced by high glucose (50 mM) perfusion were suppressed in parallel after
      pre-perfusion with 1 to 10 mM BrAcNHEtOP, dose-dependently. Five hours after
      intraperitoneal injection of BrAcNHEtOP (50 to 150 mg/kg) into mice, the Fru-6
      P,2-kinase activity and Fru-2,6-P2 concentration in livers had decreased in
      parallel, dose-dependently. These effects continued for 24 h and were accompanied
      by decreases in the fructose-1,6-bisphosphate, triose phosphates, and lactate
      contents, although the contents of glucose-6-phosphate and fructose-6-phosphate
      did not change. These results suggested that BrAcNHEtOP inactivates Fru-6-P, 2
      kinase, resulting in a decrease in the Fru-2,6-P2 level, which causes
      inactivation of phosphofructokinase and consequently inhibition of glycolysis in
      liver. Furthermore, the suppressed levels of Fru-6-P,2-kinase activity and
      metabolites in mice livers were sustained by daily injection of BrAcNHEtOP for 4
      days, and body weight gain was also suppressed during the administration of
      BrAcNHEtOP. These results suggested that BrAcNHEtOP will be a useful reagent for
      studying the role of Fru-6-P,2-kinase in vivo.

PMID- 9163525
TI  - CCAAT/enhancer-binding protein delta gene expression is mediated by APRF/STAT3.
AB  - The CCAAT/enhancer-binding protein delta (C/EBP delta) transcription factor is
      known to be rarely expressed but sharply induced at an early stage of the acute
      phase response. To investigate the regulation mechanisms for this induction, the
      5'-flanking region of the rat C/EBP delta gene was isolated. Functional analyses
      involving transfection and footprinting indicated that the upstream region up to 
      175 bp is sufficient for the full basal activity in rat fibroblast 3Y1 cells. At
      least three cis-elements including a GC box are involved in this activity. When
      HepG2 cells were treated with interleukin-6 (IL-6), C/EBP delta mRNA was rapidly
      induced. Transfection and gel shift analyses identified the binding site for the
      acute phase response factor/signal transducers and activators of transcription
      (APRF/STAT3). These findings strongly indicate that C/EBP delta gene expression
      is mediated by APRF/STAT3, which is phosphorylated for the activation through the
      IL-6 receptor when cells are treated with IL-6, and trans-activates the other
      acute phase response genes.

PMID- 9163526
TI  - Polycistronic expression and RNA-binding specificity of the C. elegans homologue
      of the spliceosome-associated protein SAP49.
AB  - Splicing of mRNA precursors (pre-mRNAs) occurs in a multimolecular complex,
      termed spliceosome, which is comprised of pre-mRNA, small nuclear
      ribonucleoprotein particles (snRNPs), and other protein factors including
      spliceosome-associated proteins (SAPs). SAP49 is thought to be a subunit of the
      essential splicing factor SF3b and is involved in U2 snRNP function in mammalian
      cells. We have isolated a Caenorhabditis elegans cDNA encoding an RNA-binding
      protein with two RNA recognition motifs (RRMs) which shows extensive similarity
      to the human SAP49. The primary transcript for this C. elegans SAP49 homologue
      (cSAP49) seems to contain at least two additional cistrons and can be processed
      into three different mature mRNAs by trans-splicing. The cSAP49 mRNA, like other
      mRNAs in the same polycistronic unit, is expressed in most of the developmental
      stages, consistent with its putative essential function for mRNA splicing. By
      means of an in vitro RNA selection system, we demonstrate that cSAP49 possesses
      specific RNA-binding activity which resides in its second RRM.

PMID- 9163527
TI  - Measurement of the membrane potential generated by complex I in submitochondrial
      particles.
AB  - To investigate the energy-conserving function of the NADH:ubiquinone reductase
      (complex I), we have selected oxonol VI [bis(3-propyl-5-oxoisoxazol-4
      yl)pentamethine oxonol] as the most sensitive probe for measuring the reactions
      of membrane potential generation in submitochondrial particles. Calibration of
      the oxonol signals with potassium diffusion potentials shows a non-linear
      response after a threshold around -50 mV. Thermodynamic evaluations indicate that
      the upper limit of the oxonol response to the potential generated by complex I is
      around -220 mV, which is close to the maximal protonmotive force in coupled
      submitochondrial particles. NADH addition to particles in which ubiquinol
      oxidation is blocked by inhibitors of other respiratory complexes generates
      oxonol signals corresponding to membrane potentials of -130 to -180 mV. These
      signals are produced by about four turnovers of the complex reducing endogenous
      ubiquinone (i.e. non-steady-state conditions) and are equivalent to a charge
      separation similar to that of the antimycin-sensitive reactions of
      ubiquinol:cytochrome c reductase (complex III). The transient oxonol signals
      under non-steady-state conditions are thus informative of crucial steps in the
      electrogenic reactions catalyzed by complex I. The possible nature of these
      electrogenic reactions is discussed in relation to proposed mechanisms for
      complex I.

PMID- 9163529
TI  - A new method for seed oil body purification and examination of oil body integrity
      following germination.
AB  - Plant seeds store triacylglycerols as energy sources for germination and
      postgerminative growth of seedlings. The triacylglycerols are preserved in small,
      discrete, intracellular organelles called oil bodies. A new method was developed
      to purify seed oil bodies. The method included extraction, flotation by
      centrifugation, detergent washing, ionic elution, treatment with a chaotropic
      agent, and integrity testing by use of hexane. These processes subsequently
      removed non-specifically associated or trapped proteins within the oil bodies.
      Oil bodies purified by this method maintained their integrity and displayed
      electrostatic repulsion and steric hindrance on their surface. Compared with the
      previous procedure, this method allowed higher purification of oil bodies, as
      demonstrated by SDS-PAGE using five species of oilseeds. Oil bodies purified from
      sesame were further analyzed by two-dimensional gel electrophoresis and revealed
      two potential oleosin isoforms. The integrity of oil bodies in germinating sesame
      seedlings was examined by hexane extraction. Our results indicated that
      consumption of triacylglycerols reduced gradually the total amount of oil bodies
      in seedlings, whereas no alteration was observed in the integrity of remaining
      oil bodies. This observation implies that oil bodies in germinating seeds are not
      degraded simultaneously. It is suggested that glyoxisomes, with the assistance of
      mitochondria, fuse and digest oil bodies one at a time, while the remaining oil
      bodies are preserved intact during the whole period of germination.

PMID- 9163528
TI  - Sialic acid-binding motif of Maackia amurensis lectins.
AB  - Maackia amurensis hemagglutinin (MAH) and leukoagglutinin (MAL) are leguminous
      lectins which recognize carbohydrate chains containing sialic acid residues
      linked alpha2,3 to penultimate galactose residues. In the present investigation,
      cDNA clones encoding MAL were isolated from a cDNA library constructed from
      germinated Maackia amurensis seeds and sequenced. From the reading frame of the
      cloned cDNAs, MAL was predicted to be composed of 287 amino acid residues, and
      showed strong similarity to MAH (86.2% identity). In leguminous lectins, most
      amino acid residues involved in sugar-binding were previously shown to be
      conserved. However, in both MAL and MAH lectins, the conserved glycine and
      asparagine were shown to be substituted by lysine and aspartic acid,
      respectively. Substitutions were made at position 105 and/or 135 of MAH to
      examine the roles of amino acid residues postulated to be important in binding to
      sialic acids. Recombinant MAH bound to the sialic acid-containing CB-II
      glycopeptide of human glycophorin A. By contrast, mutant lectins with lysine-105
      substituted with glycine and/or aspartic acid-135 with asparagine did not bind to
      sialic acid residues. This indicates that these characteristic substitutions are
      important in sialic acid binding.

PMID- 9163530
TI  - Biochemical and immunological characterization of deoxyhypusine synthase purified
      from the yeast Saccharomyces carlsbergensis.
AB  - Deoxyhypusine synthase catalyzes the NAD+-dependent formation of deoxyhypusine in
      the eIF-5A precursor protein by transferring the 4-aminobutyl moiety of
      spermidine. This enzyme has recently been shown to be essential for cell
      viability and growth of yeast [Sasaki, K., Abid, M.R., and Miyazaki, M. (1996)
      FEBS Lett. 384, 151 154]. We have purified and characterized the enzyme from the
      yeast Saccharomyces carlsbergensis. The yeast and recombinant enzymes had a
      specific activity of 1.21 to 1.26 pmol per min per pmol of protein, and
      recognized both the eIF-5A precursor proteins almost equally as judged from their
      similar K(m) and V(max) values. Size exclusion chromatography and SDS-PAGE
      indicated that the active form of the enzyme is a homotetramer consisting of 43
      kDa subunits. The enzyme showed a strict specificity for its substrates, NAD+,
      spermidine and eIF-5A precursor protein. Among all the substrates tested, only
      NAD+ showed a protective effect against heat inactivation of the enzyme
      suggesting that NAD+ initiates some conformational change in the enzyme. NADH
      exhibited a strong non-competitive inhibition (product inhibition). Unexpectedly,
      FAD, FMN, and riboflavin showed a moderate competitive inhibition. The
      competitive inhibition by diamines was maximal with compounds resembling
      spermidine in carbon chain length. 1,3-Diaminopropane inhibited the enzyme
      strongly in a competitive manner (product inhibition). On the other hand,
      putrescine did not inhibit the enzyme or act as a substrate. A polyclonal
      antibody raised against the yeast recombinant enzyme specifically inhibited
      deoxyhypusine synthase activity. The cross-reactivity (by Western blotting) of
      this antibody with the crude extracts varied depending on the source, indicating
      species specificity.

PMID- 9163532
TI  - Linear polymerization caused by the defective folding of a non-inhibitory serpin
      ovalbumin.
AB  - Polymerization caused by defective folding of heat-denatured ovalbumin was
      examined. A compactly misfolded ovalbumin that was produced by cooling heat
      denatured protein rapidly tended to aggregate in the presence of salt. Two
      different forms of aggregates were observed as the concentration of salt was
      varied: a linear polymer at a physiological concentration and a massive
      agglomerate at a higher concentration. Salt-induced polymerization depended on
      the species of anion and the order of effectiveness followed the lyotropic series
      of Hofmeister. Defective folding of heat-denatured ovalbumin induced the exposure
      of cysteine residues in sequences located in the interior of the native protein.
      The misfolded ovalbumin, but not the native protein, bound to bovine BiP and
      stimulated its ATPase activity with the K(m) of 64 microM and the V(max) of 0.5
      nmol/min per milligram. Measurement of surface plasmon resonance revealed that
      only the misfolded ovalbumin was recognized with the K(d) of 4.12 X 10(-8) M by
      the Fab fragment of a monoclonal antibody raised against hen ovalbumin, and its
      epitope was determined to be a hydrophobic segment in the beta-strand of central
      sheet A. Transmission electron microscopy showed that the linear polymerization
      was inhibited by the addition of bovine BiP and the Fab fragment. These results
      demonstrated that the compactly misfolded ovalbumin polymerized through
      hydrophobic interaction occurring among the areas exposed as a result of
      defective folding of the heat-denatured protein. Exposure of the region of, or
      adjacent to, the central beta-sheet A was required for axial contact among the
      misfolded molecules, suggesting that this process may be explained by reference
      to the mechanism proposed for loop-sheet polymerization in the Z type variant of
      a serpin alpha1-antitrypsin.

PMID- 9163531
TI  - Structural feature of the major but not cytokine-inducing molecular species of
      lipoteichoic acid.
AB  - Previously, lipoteichoic acid (LTA) of Enterococcus hirae was found to exhibit
      definite cytokine-inducing activity but synthetic specimens which share the
      fundamental structural principles proposed for LTA had no corresponding activity.
      We also showed recently that several minor components totally less than 5% of the
      LTA fraction from E. hirae ATCC 9790 possessed the activity, whereas the major
      component (over 90%) did not [Suda, Y., Tochio, H., Kawano, K., Takada, H.,
      Yoshida, T., Kotani, S., and Kusumoto, S. (1995) FEMS Immun. Med. Microbiol. 12,
      97-112]. In the present study, the structure of the major component of LTA was
      studied in an attempt to elucidate the reason for the lack of the activity in the
      synthetic compounds. The major component of the LTA was first digested by
      hydrofluoric acid hydrolysis to cleave phosphodiester linkages present. The
      hydrolysis products were separated and characterized by means of NMR and MS. The
      linkage positions of the original phosphodiesters were determined from the NMR
      spectra of an alkali-treated product without hydrofluoric acid degradation. The
      compound was proved to consist of 1,3-linked poly(glycerophosphate) and a lipid
      anchor, Glc(alpha1-2)Glc(alpha1-3)acyl(2)Gro, the former being linked to the 6
      position of the distal glucose of the latter. The 2-position of the glycerol
      residues in the glycerophosphate part were substituted by oligoglucose esterified
      partially with alanine. The gross structure elucidated here thus coincides with
      the previous conclusion described by Fischer [Fischer, W. (1990) in Glycolipids,
      Phosphoglycolipids and Sulfoglycolipids (Kates, M., ed.) pp. 123 234, Plenum
      Press, New York]. Thus, the molecular species with this so-called "LTA structure"
      is not responsible for the cytokine-inducing activity.

PMID- 9163533
TI  - Structural and functional characterization of the human brain D-aspartate
      oxidase.
AB  - D-Aspartate oxidase (DDO) cDNAs were isolated from the human brain RNA using the
      RT-PCR method. Two forms (DDO-1 and DDO-2) of DDO mRNA were detected. Structural
      analysis of the DDO cDNAs and genomic DNA showed that DDO-1 and DDO-2 are
      produced by alternative splicing from a single gene. A protein encoded by the DDO
      1 cDNA consists of 341 amino acids, and the amino acid sequence of DDO-2 was
      identical to that of DDO-1 except for the absence of 59 amino acids covering
      residues 95-153 of DDO-1. A homogenous preparation of DDO-1 was obtained using an
      expression system in Escherichia coli. DDO-1 selectively catalyzed the oxidative
      deamination of D-aspartate and its N-methylated derivative, N-methyl D-aspartate;
      the values of K(m) and k(cat) for D-aspartate were 2.7 mM and 52.5 mol D
      aspartate oxidized x s(-1) x mol(-1) and those for N-methyl D-aspartate were 6.8
      mM and 37.7 mol N-methyl D-aspartate oxidized x s(-1) x mol(-1), respectively.

PMID- 9163534
TI  - Studies on the site of phosphorylation of Ca2+/calmodulin-dependent protein
      kinase (CaM-kinase) IV by CaM-kinase kinase.
AB  - The phosphorylation site(s) involved in the activation of CaM-kinase IV by CaM
      kinase kinase alpha was studied using a mutant CaM-kinase IV (K71R) in which
      Lys71 (ATP-binding site) was replaced with Arg, because the autophosphorylation
      of CaM-kinase IV occurring at multiple sites made it difficult to study
      phosphorylation of the enzyme by CaM-kinase kinase. Sequence analysis of the
      phosphopeptide from the trypsin digest of CaM-kinase IV (K71R) phosphorylated by
      CaM-kinase kinase alpha suggested that the phosphorylation of CaM-kinase IV by
      CaM-kinase kinase only occurred at Thr196. The recombinant mutant CaM-kinase IV
      in which Thr196 or Thr200 was replaced with nonphosphorylatable alanine showed
      little activity in the presence and absence of the kinase kinase. The mutant
      enzyme in which Thr196 was replaced with negatively charged aspartic acid showed
      almost 25 times as high activity as the wild-type enzyme in the absence of the
      kinase kinase, and no more activation was observed in its presence. In contrast,
      the enzyme in which Thr200 was replaced with aspartic acid showed little enzyme
      activity. Thus, it may be concluded that the phosphorylation of Thr196 in CaM
      kinase IV by CaM-kinase kinase is necessary for the subsequent
      autophosphorylation and activation of CaM-kinase IV.

PMID- 9163535
TI  - Effects of volatile anesthetics on hippocampal slice metabolism, response to
      anoxia with and without glucose.
AB  - Anesthetics attenuate ischemic damage and so are often not used when preparing
      hippocampal slices for studies of ischemic or anoxic damage. In this study, we
      tested whether halothane, ether or isoflurane, when used briefly during slice
      preparation, have persistent effects on slice ATP metabolism, protein synthesis
      or morphology. We also tested the effects of anoxia with and without glucose on
      these slices. Five minutes of anoxia without glucose (anoxia-aglycemia) caused a
      dramatic depletion of ATP to less than 22% of control levels, a persistent
      inhibition of neuronal protein synthesis to less than 10% of control rates and
      severe morphological damage. Slices prepared using volatile anesthetics showed
      the same degree of damage due to anoxia-aglycemia, when compared with untreated
      tissue. In contrast, 5 min anoxia caused a 40% decrease in ATP levels in
      untreated tissue, but did not damage protein synthesis or morphology. While
      isoflurane-treated tissue responded identically to anoxia as untreated tissue,
      both halothane and ether prevented the anoxic ATP fall. These findings suggest
      that while halothane and ether may have persistent effects on slice responses to
      anoxia, isoflurane is a good candidate anesthetic for slice preparation
      procedures.

PMID- 9163536
TI  - The differential contribution of capsaicin-sensitive afferents to behavioral and
      cardiovascular measures of brief and persistent nociception and to Fos expression
      in the formalin test.
AB  - Intraplantar injection of dilute formalin evokes brief (Phase 1) and persistent
      (Phase 2) increases in primary afferent activity, pain behavior, and
      cardiovascular responses, and induces spinal cord Fos-like immunoreactivity (Fos
      LI). Although previous studies demonstrated that the destruction of small
      diameter primary afferents with neonatal capsaicin treatment decrease formalin
      evoked nociception, these studies only evaluated behavioral responses, and did
      not distinguish between Phase 1 and 2. To address these questions, we
      simultaneously evaluated formalin-evoked pain behavior (flinching of the
      afflicted paw), cardiovascular responses (heart rate and mean arterial pressure),
      and lumbar spinal cord Fos expression in control rats and in rats treated with
      capsaicin (100 mg/kg) one day postpartum. We found that neonatal capsaicin
      treated rats, compared to controls, exhibited similar cardiovascular responses
      and slightly less flinching behavior during Phase 1. During Phase 2, however,
      capsaicin-treated rats exhibited 59% less flinching and 45% smaller heart rate
      responses. Also, in capsaicin-treated rats, we counted 59% fewer Fos-labeled
      neurons in the spinal cord. These results indicate that capsaicin-sensitive
      afferents contribute to formalin-evoked behavioral and cardiovascular responses
      and to spinal cord neuronal responses. The differential effect of neonatal
      capsaicin on nociception during Phase 1 and Phase 2 suggests that sensitization
      mechanisms during Phase 1 do not contribute to the magnitude of nociceptive
      responses during Phase 2.

PMID- 9163537
TI  - Discriminable excitotoxic effects of ibotenic acid, AMPA, NMDA and quinolinic
      acid in the rat laterodorsal tegmental nucleus.
AB  - Excitotoxins are valuable tools in neuroscience research as they can help us to
      discover the extent to which certain neurones are necessary for different types
      of behaviour. They have distinctive neurotoxic effects depending on where they
      are infused, and this study was conducted to delineate the neurotoxic profiles of
      excitotoxins in the laterodorsal tegmental nucleus (LDTg). Two 0.1 microl
      infusions of 0.1 M ibotenate, 0.1 M quinolinate, 0.04-0.1 M NMDA, or 0.05-0.015 M
      AMPA, were made unilaterally into the LDTg under either pentobarbitone or Avertin
      anaesthesia. The injection needle was oriented at an angle of 24 degrees from
      vertical in the mediolateral plane. After 23-27 days, sections through the
      mesopontine tegmentum were processed using standard histological procedures for
      NADPH-diaphorase histochemistry, tyrosine hydroxylase or 5-hydroxytryptamine
      immunohistochemistry, and Cresyl violet. Lesions were assessed in terms of the
      size of the damaged area (identified by reactive gliosis), the extent of
      cholinergic cell loss in the mesopontine tegmentum (by counting NADPH-diaphorase
      positive neurones), and neuronal loss induced in the locus coeruleus and dorsal
      raphe nucleus. Ibotenate induced compact lesions in the LDTg (more than 80%
      cholinergic loss) and did little damage to the locus coeruleus and dorsal raphe
      nucleus. Quinolinate and low doses of AMPA and NMDA made very small lesions with
      less than 35% cholinergic loss, while at higher doses, AMPA and NMDA induced
      large areas of reactive gliosis but killed only a proportion of the cholinergic
      neurones. AMPA appeared to have a particular affinity for noradrenergic neurones
      in the locus coeruleus, with the 0.015 M dose injected into the LDTg typically
      destroying the majority of these neurones. The results are discussed in the
      context of what is known about the mechanisms of excitotoxins and the glutamate
      receptor profile of mesopontine neurones.

PMID- 9163538
TI  - Mossy fibre reorganization in the hippocampus of prion protein null mice.
AB  - Mice lacking prion protein (PrP-null) are resistant to transmissible spongiform
      encephalopathies. However, the normal functions of this highly conserved protein
      remain controversial. This study examines whether PrP-null mice develop normal
      neuronal pathways, specifically the mossy fibre pathway, within the hippocampus.
      Timm stained hippocampal sections from the PrP-null group had more granules than
      the controls in: the granule cell layer, the inner molecular layer of the dentate
      gyrus, and the infrapyramidal region of CA3. This resembles the mossy fibre
      collateral and terminal sprouting seen in certain epilepsies. The abnormal
      connectivity might be predicted to promote epileptiform activity, but
      extracellular electrophysiological recordings from the granule cell layer
      revealed a reduced excitability in the PrP-null group, both with and without
      blockade of GABA(A) receptor-mediated inhibition. We propose that reorganization
      of neuronal circuity is a feature of PrP-null mice.

PMID- 9163539
TI  - Neuroprotection by both NMDA and non-NMDA receptor antagonists in in vitro
      ischemia.
AB  - We have investigated the relative contributions of oxygen and glucose deprivation
      to ischaemic neurodegeneration in organotypic hippocampal slice cultures.
      Cultures prepared from 10-day-old rats were maintained in vitro for 14 days and
      then deprived of either oxygen (hypoxia), glucose (hypoglycaemia), or both oxygen
      and glucose (ischaemia). Hypoxia alone induced degeneration selectively in CA1
      pyramidal cells and this was greatly potentiated if glucose was removed from the
      medium. We have also characterised the effects of both pre- and post-treatment
      using glutamate receptor antagonists and the sodium channel blocker tetrodotoxin
      (TTX). Neuronal death following either hypoxia or ischaemia was prevented by pre
      incubation with CNQX, MK-801 or tetrodotoxin. MK-801 or CNQX also prevented death
      induced by either hypoxia or ischaemia if added immediately post-insult, however,
      post-insult addition of TTX prevented hypoxic but not ischaemic damage.
      Organotypic hippocampal slice cultures are sensitive to both NMDA and non-NMDA
      glutamate receptor blockade and thus represent a useful in vitro system for the
      study of ischaemic neurodegeneration paralleling results reported using in vivo
      models of ischaemia.

PMID- 9163540
TI  - Dynamic responses of presynaptic terminal membrane pools following KCl and
      sucrose stimulation.
AB  - The cholinergic presynaptic terminals of Torpedo electric organ have been
      examined morphometrically following stimulation by KCI and sucrose. The objective
      was to confirm correlations predicted by the vesicle hypothesis between miniature
      end-plate potentials (MEPPs) and morphometric changes in terminal ultrastructure.
      Both secretegogues generated high frequencies of MEPPs and also distinctive
      though differing ultrastructural changes. The synaptic vesicles show classes of
      68 and 90 nm diameters and both store acetylcholine (ACh). KCl stimulation
      depleted the 90 nm class first whereas sucrose reversed the order of depletion.
      Very few instances of actual vesicle fusion were seen. Dose-response correlations
      between vesicle density and secretegogue strength (mM) and duration were higher
      with sucrose. Both secretegogues produced declines in vesicle numbers and
      densities and yielded multimodal distributions of large vesicles with an average
      160 nm mean diameter. No meaningful correlations were detected between numbers of
      MEPPs and vesicles and little evidence was found to indicate that vesicles were
      fusing to terminal plasma membrane in numbers approximating MEPP release. Linear
      regression analysis was used to quantitatively examine relationships between the
      vesicle membrane pool and other pools of the putative exo/endocytotic pathway.
      Correlation coefficients between vesicle and terminal plasma membrane pools were
      non-significant and of positive sign, indicating independent, similar responses.
      Non-significant, negative coefficients were obtained when vacuole and 160 nm
      vesicle membrane values were included. These tests further argue against claims
      that vesicles are actively fusing with the plasma membrane. These conflicting
      findings for both secretegogues preclude meaningful correlations between vesicle
      changes and numbers of MEPPs generated and again emphasize the difficulty of
      validating the vesicle hypothesis by ultrastructural means. On the other hand,
      the study shows that vesicular, vacuolar and terminal membrane pools are
      dynamically changing during transmitter release, presumably interacting with
      cytosolic membrane constituents. A dynamical release process therefore has been
      proposed to account for the two classes of MEPPs, the rapid changes in class
      ratio and the mutable characteristics of the bell-MEPP that presently challenge
      the quantal-vesicular claims of prepackaged, immutable, exocytotically released
      packets of transmitter. This model features a state for each MEPP class with
      class and size determined at moment of release. For example, a single flicker of
      a channel would generate the sub-MEPP (defined subunit of an MEPP) and 7-20
      flickering channels would generate the bell-MEPP.

PMID- 9163541
TI  - Effects of thymosin alpha1 on the development of amoeboid microglial cells in the
      corpus callosum of neonatal BALB/c and athymic mice.
AB  - The present study investigated the effects of intraperitoneal injections of
      thymosin alpha1 on the supraventricular amoeboid microglial cells (SAMC) in the
      newborn athymic and normal BALB/c mice. The microglial cells labelled by the
      lectin GSA I-B4 and the antibody Mac-1 showed a 27% reduction in number in the
      athymic mice receiving thymosin alpha1 injections compared with those receiving
      vehicle injections, and a 37% reduction in BALB/c mice receiving thymosin alpha1
      injections compared with those receiving vehicle injections. Some of the SAMC in
      both BALB/c and athymic mice receiving thymosin alpha1 injections became
      ramified, while the remainder still exhibited their normal amoeboid appearance
      with few filopodial processes. Ultrastructurally, the lectin reaction product was
      confined to the plasma membrane and some cytoplasmic vacuoles of labelled SAMC.
      In both BALB/c and athymic mice, some labelled microglial cells became slender or
      elongated after thymosin alpha1 injections. Also their cytoplasm was reduced and
      contained fewer organelles. Radioimmunoassay of the plasma of thymosin alpha1 and
      vehicle-injected mice showed that there was a significant increase in the
      cortisol level in BALB/c (P < 0.01) and athymic (P < 0.001) mice 5 days after
      thymosin alpha1 injections, compared with that of the control mice. The results
      point to a strong correlation between the reduction of SAMC and the increased
      level of plasma cortisol. Supporting this is the fact that cortisol is known to
      suppress the production of monocytes considered to be the precursors of amoeboid
      microglia.

PMID- 9163542
TI  - Brain incorporation of [1-11C]arachidonate in normocapnic and hypercapnic
      monkeys, measured with positron emission tomography.
AB  - Positron emission tomography (PET) was used to determine brain incorporation
      coefficients k* of [1-11C]arachidonate in isoflurane-anesthetized rhesus monkeys,
      as well as cerebral blood flow (CBF) using [15O]water. Intravenously injected [1
      11C]arachidonate disappeared from plasma with a half-life of 1.1 min, whereas
      brain radioactivity reached a steady-state by 10 min. Mean values of k* were the
      same whether calculated by a single-time point method at 20 min after injection
      began, or by least-squares fitting of an equation for total brain radioactivity
      to data at all time points. k* equalled 1.1-1.2 x 10(-4) ml x s(-1) x g(-1) in
      gray matter and was unaffected by a 2.6-fold increase in CBF caused by
      hypercapnia. These results indicate that brain incorporation of [1
      11C]arachidonate can be quantified in the primate using PET, and that
      incorporation is flow-independent.

PMID- 9163543
TI  - Elevated hypothalamic neuropeptide Y levels in rats with dorsomedial hindbrain
      lesions.
AB  - Lesions centered on the area postrema (AP) and adjacent nucleus of the solitary
      tract (AP/mNTS-lesions) are reported to result in increased consumption of highly
      palatable diets. Recent studies suggest that neuropeptide Y (NPY) may cause a
      preference for carbohydrate-rich diets. Thus, it is possible that NPY may play a
      role in the enhanced intake of highly palatable diets by AP/mNTS-lesioned rats.
      In the studies reported here, we found that lesions centered on the AP result in
      increased levels of NPY-immunoreactivity in the paraventricular nucleus of the
      hypothalamus. Additionally, steady-state NPY mRNA in the basomedial hypothalamus
      including the arcuate nucleus was elevated. Enhanced NPY was not found throughout
      the hypothalamus however, as NPY-immunoreactivity was not elevated in the lateral
      hypothalamus or the tissue bordering the anteroventral third ventricle. These
      data suggest the possibility that elevated hypothalamic NPY, particularly in the
      arcuate and paraventricular nuclei, may contribute to the altered food intake and
      energy balance observed in rats with lesions centered on the AP.

PMID- 9163544
TI  - Retinal neurones containing kainate receptors are influenced by exogenous kainate
      and ischaemia while neurones lacking these receptors are not -- melatonin
      counteracts the effects of ischaemia and kainate.
AB  - The present experiments were carried out on three types of neurone in primary
      rabbit retinal cultures. One cell-type, bipolar neurones, have glutamate APB-type
      metabotropic receptors and can be identified by the presence of thetaPKC
      immunoreactivity. The other two cell-types are primarily amacrine cells and can
      be 'stained' for the localisation of GABA immunoreactivity or for serotonin taken
      up from the medium. Most of the serotonin-accumulating and GABA-containing
      neurones contain glutamate kainate-type receptors. Exposure of the cultures to
      treatment of kainate (50 microM) or experimental ischaemia (8 h followed by 16 h
      reoxygenation) produced essentially similar findings. The serotonin-accumulating
      and GABA cells were affected as they were drastically reduced in numbers while
      the numbers of thetaPKC-containing cells were unaffected. Inclusion of the
      kainate/AMPA antagonist CNQX (100 microM) or melatonin (100 microM) to the medium
      during kainate or ischaemia treatments largely prevented the detrimental
      influences on the serotonin-accumulating and GABA cells. It is concluded that
      during experimental ischaemia excessive glutamate is released to influence cells
      which contain kainate and APB-type receptors. However, only the neurones
      containing the kainate receptors are negatively affected with the generation of
      free radicals. Melatonin or CNQX protects against this effect by scavenging free
      radicals or acting at the receptor level, respectively.

PMID- 9163545
TI  - Synaptic contacts between gonadotropin-releasing hormone-containing fibers and
      neurons in the suprachiasmatic nucleus and perichiasmatic area: an anatomical
      substrate for feedback regulation?
AB  - The suprachiasmatic nucleus (SCN) is critically involved in the generation and
      entrainment of circadian rhythms in mammalian species. Both the occurrence and
      the timing of the luteinizing hormone surge on the afternoon of proestrus in the
      female rodent are critically dependent on the integrity of the SCN. Recently, we
      demonstrated the presence of a monosynaptic pathway from the SCN to the
      gonadotropin releasing hormone (GnRH) neurons in the preoptic area. In addition,
      we found that interaction between the SCN and the GnRH system may be found close
      to the SCN, since we observed apposition of SCN efferents and GnRH fibers at the
      ultrastructural level in that region. The aim of the present study was to
      investigate the presence of synaptic contacts between GnRH fibers and structures
      in the SCN and surrounding perichiasmatic area (periSCN). At the light
      microscopical level, the immunoreactivity for GnRH showed a considerable overlap
      with the immunoreactivity for vasopressin and vasoactive intestinal peptide, two
      neuropeptides synthesized by SCN neurons. At the ultrastructural level, we
      demonstrated synaptic input of GnRH-containing axons on immunocytochemically
      unidentified structures in the SCN/peri-SCN region. The present results clearly
      demonstrate that the SCN and periSCN are postsynaptic targets of GnRH fibers. It
      is hypothesized that the GnRH input in the SCN region represents an anatomical
      substrate for feedback-control between these systems.

PMID- 9163546
TI  - The serotonergic projection from the median raphe nucleus to the suprachiasmatic
      nucleus modulates activity phase onset, but not other circadian rhythm
      parameters.
AB  - The suprachiasmatic nucleus (SCN) is densely innervated by serotonergic fibers
      originating in the median raphe nucleus (MR). Serotonin (5-HT) specific lesions
      of the MR alter entrainment and eliminate 5-HT fibers in the SCN, as well as in
      all other MR-recipient areas. The present study used 5-HT specific lesions of the
      SCN or the MR to determine the role of 5-HT in the SCN as a regulator of
      entrainment. Neurotoxic lesions of the MR significantly reduced 5-HT cell bodies
      in that nucleus and eliminated essentially all 5-HT innervation of the SCN. As
      previously demonstrated, these anatomical changes were associated with an advance
      in activity onset, delay in offset and expansion of the activity phase (alpha).
      Neurotoxin directly applied to the SCN caused an advance in the average activity
      onset, but had no effect on offset or alpha. About half of the SCN lesion animals
      had onsets equivalent to the MR lesion group, whereas onsets of the remaining
      animals were normal. Loss of SCN 5-HT innervation was severe for all SCN lesion
      animals, but significantly greater for those with advanced activity onsets. These
      results suggest that although the 5-HT projection to the SCN is likely to be
      responsible for modulating activity onset, the timing of activity offset appears
      to be regulated by a MR projection to an area outside the SCN. Furthermore,
      surprisingly few 5-HT fibers in the SCN are sufficient to maintain the normal
      phase angle of entrainment.

PMID- 9163547
TI  - Uncoupling of GABA(A) and benzodiazepine receptor binding activity in the
      hippocampal formation of schizophrenic brain.
AB  - A recent postmortem study has reported that there is a widespread upregulation of
      GABA(A) receptor binding activity throughout most subregions of the hippocampal
      formation of schizophrenic brain. The current study has been undertaken to
      determine whether the benzodiazepine (BZ) receptor, which is a component of the
      GABA(A) receptor complex, may also be upregulated in schizophrenics. Using a low
      resolution film autoradiographic technique to localize [3H]flunitrazepam binding,
      the subregional and laminar distribution of specific BZ receptor binding was
      found to parallel that of the GABA(A) site, except in the area dentata where BZ
      binding was approximately 73% higher in the outer molecular layer. When BZ
      receptor binding was compared in the same normal control (n = 15) and
      schizophrenic (n = 8) cases in which the GABA(A) receptor was analyzed, there
      were very few differences noted between the two groups, except for small, though
      significant, increases in the stratum oriens of CA3 (30%), the subiculum (20-30%)
      and the presubiculum (15-20%) of the patient group. These latter increases
      overlapped with the subregions and laminae in schizophrenics showing the most
      marked increases of GABA(A) receptor binding. Using a high-resolution technique
      to evaluate specific BZ receptor binding on different neuronal subtypes, no
      difference was observed on either pyramidal or nonpyramidal neurons of sector CA3
      where GABA(A) receptor activity had been found to be significantly increased on
      the latter neuronal subtype. The potential confounding effects of age, postmortem
      interval and exposure to either benzodiazepine or neuroleptic drugs do not
      account for the lack of marked differences in BZ receptor binding in the
      schizophrenic group. Taken together, the results of this study are consistent
      with the possibility that defective GABAergic integration in schizophrenia may be
      associated with an uncoupling in the regulation of the GABA(A) and BZ receptors.

PMID- 9163548
TI  - Sleep in rats rendered chronically hyperprolactinemic with anterior pituitary
      grafts.
AB  - A hyperprolactinemic rat model [rats bearing anterior pituitary grafts under the
      capsule of the kidney (AP-grafted rats)] was used to study sleep-wake activity
      and cortical brain temperature (T(crt)). Fisher 344 male rats (n = 24) were
      implanted with anterior pituitaries from rat pups; the control rats (n = 12) were
      sham-operated. Sleep-wake activity and T(crt) were recorded for 2 days between
      weeks 3 and 7 after surgery. The hyperprolactinemic state of the rats was
      confirmed by plasma prolactin (PRL) assays on week 7 and by determination of PRL
      mRNA levels in the anterior pituitary of the AP-grafted rats. Neither growth
      hormone plasma concentration nor pituitary mRNA levels were affected by the
      pituitary grafts. Duration of non-rapid eye movement sleep (NREMS) was slightly
      enhanced in the AP-grafted rats. A large increase in rapid eye movement sleep
      (REMS) during the 12-h light period was the major effect of the implantation of
      the extra pituitaries. Both the duration and the frequency of the REMS episodes
      increased and persisted for weeks 4-7 post-implantation. The nocturnal states of
      vigilance, T(crt), and intensity of NREMS (EEG slow wave activity) were not
      altered. The results clearly indicate that the enhancements in REMS persist
      during hyperprolactinemia, and support the hypothesis that PRL possesses REMS
      promoting activity.

PMID- 9163549
TI  - A non-thalamic pathway contributes to a whole body map in the brain of the
      budgerigar.
AB  - Nucleus basalis (Bas) of the budgerigar contains an ordered, but distorted,
      somatotopic representation of the whole body, as does the primary somatosensory
      cortex (SI) of mammals. Unlike SI, however, the beak and body regions of Bas
      receive their sensory input via disynaptic pathways relaying in the pons. That to
      the body parts originates in a previously undescribed nucleus that receives its
      inputs from primary afferents via a novel, ipsilateral somatosensory pathway.

PMID- 9163550
TI  - Cerebral blood flow regulation in neonatal rabbits is altered by chronic cocaine
      administration.
AB  - Maternal cocaine abuse has several deleterious effects in the newborn, including
      perinatal asphyxia, hypoxia, and hypercapnia. We hypothesized that chronic
      cocaine exposure during development may alter cerebral blood flow (CBF)
      regulation. We studied 16 neonatal rabbits that had received cocaine (20 mg/kg,
      i.p. b.i.d.) or saline since birth. Changes in CBF were measured by laser doppler
      flowmetry before (baseline), and during hypercapnia (FiCO2 = 7.5%), hypoxia (FiO2
      = 12%), and asphyxia (apnea for 1 min). During hypercapnia, CBF increased less in
      cocaine than in control animals (28 +/- 3% vs. 69 +/- 10%, P < 0.05). During
      hypoxia, CBF increased similarly in both groups. During reventilation after
      asphyxia, CBF increased more in cocaine than in control animals (391 +/- 52% vs.
      225 +/- 43%, P < 0.05). Chronic cocaine exposure during brain development appears
      to alter CBF regulation to hypercapnia and asphyxia, which may put the drug
      exposed newborn at risk for neurologic injury around birth.

PMID- 9163552
TI  - Demonstration of the corticotectobulbar pathway from the orofacial motor cortex
      to the parvicellular reticular formation in the rat.
AB  - We examined a corticotectobulbar pathway from the orofacial motor cortex (OfM) to
      the parvicellular reticular formation (RFp), where numerous premotor neurons for
      the orofacial motor nuclei were known to be distributed, light and electron
      microscopically by using a combination of anterograde and retrograde tracing
      techniques. After contralateral injections of biotinylated dextranamine (BDA)
      into the OfM and cholera toxin B subunit (CTb) into the RFp, the overlapping
      distribution of ipsilateral axon terminals labeled with BDA and contralateral
      neurons labeled with CTb was found in the lateralmost part of the superior
      colliculus (SC). Furthermore, contralateral injections of BDA into the OfM and
      wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the RFp resulted in
      that ipsilateral axons labeled with BDA made asymmetrical synaptic contacts with
      the dendrites of contralateral SC neurons labeled with WGA-HRP.

PMID- 9163551
TI  - Connexin43 immunoreactivity in the catfish retina.
AB  - We used antibodies directed against rat heart connexin43 (Cx43) to perform
      immunoblot and immunohistochemical (IHC) analyses of the catfish retina. The
      antibodies recognized a retinal protein which co-migrated with mouse brain Cx43.
      IHC staining resulted in punctate labeling of the external limiting membrane and
      the outer nuclear layer. Although infrequent, labeling was also observed in the
      inner nuclear layer. These results suggest that a Cx43 isoform may be present in
      Muller glial cells and neurons of the distal catfish retina.

PMID- 9163553
TI  - Effect of adrenalectomy on cocaine facilitation of lateral hypothalamic self
      stimulation.
AB  - An emerging body of evidence indicates that the adrenal hormone corticosterone
      modulates behavioral effects of abused drugs. Recently, it was reported that the
      self-administration and locomotor stimulatory effect of cocaine are blocked by
      adrenalectomy (ADX). In order to evaluate the effect of ADX on the brain reward
      system in general, and cocaine reward in particular, the effect of ADX on lateral
      hypothalamic self-stimulation (LHSS) and its facilitation by cocaine were
      investigated. Using curve-shift methodology, effects of cocaine (1.0, 3.0 and
      10.0 mg/kg, i.p.) on the rewarding efficacy of brain stimulation were determined
      in ADX rats, with and without corticosterone supplementation, and compared with
      sham-operated controls. Results indicate that ADX does not affect LHSS or the
      facilitatory effect of cocaine. The divergence between these results and the
      results of cocaine self-administration studies is discussed in terms of the
      neuroanatomical and psychological processing of reward.

PMID- 9163554
TI  - Involvement of calmodulin-dependent protein kinases-I and -IV in long-term
      potentiation.
AB  - Multifunctional Ca2+/calmodulin-dependent protein kinases (CaMKs) are thought to
      be involved in the induction of long-term potentiation (LTP). In the present
      study, LTP was induced by theta burst stimulation in the Schaffer collateral area
      of the stratum radiatum in the hippocampal CA1 region of the rat hippocampus. LTP
      induced and control hippocampal slices were studied by Western blot and
      immunohistochemical analyses using CaMK-I, -II and -IV antibodies. Increased
      amounts of all three CaMKs were found in LTP-induced hippocampal slices as
      indicated by Western blot as well as by the density of their immunoreactivity.
      Our data clearly shows that not only CaMK-II but also CaMK-I and -IV contribute
      to synaptic plasticity formed in LTP.

PMID- 9163555
TI  - Intracerebroventricular injection of mammalian and chicken glucagon-like peptide
      1 inhibits food intake of the neonatal chick.
AB  - Glucagon-like peptide-1 (GLP-1), structurally similar to glucagon, is synthesized
      from a larger precursor, preproglucagon, and has been postulated to be a novel
      incretin. Recently, it was reported that central administration of GLP-1
      decreased food intake in rats. The amino acid sequences of GLP-1 are identical in
      all mammals, and chicken GLP-1 exhibits a high homology with mammalian GLP-1. The
      aim of this study was to elucidate whether central injection of mammalian or
      chicken GLP-1 inhibits food intake in the chick, and to compare their effects.
      Intracerebroventricular administration of mammalian and chicken GLP-1 strongly
      inhibited food intake of chicks. However, the suppressive effect of both GLP-1 on
      food intake was similar. These results show that GLP-1 with a variety of amino
      acid sequences may be the most potent inhibitor of food intake in the chicken.

PMID- 9163556
TI  - Asymmetrical regulation of blood pressure in the rat medulla.
AB  - The effects of microinjection of serotonin-1 (5-HT1) antagonist methiothepin and
      5-HT1 agonist buspirone into the nucleus reticularis parvocellularis were
      investigated in the anaesthetized rats. Methiothepin produced an increase in
      arterial blood pressure when injected into the left side, but it did a decrease
      when injected into the right side. On the contrary, buspirone produced a decrease
      in arterial blood pressure when injected into the left side, but it did an
      increase when injected into the right side. These findings provide the clue to
      clarify that there is a reciprocal regulation of arterial blood pressure between
      the left and right sides in the rat medulla.

PMID- 9163557
TI  - alpha2,3-sialyltransferase mRNA and alpha2,3-linked glycoprotein sialylation are
      increased in malignant gliomas.
AB  - CMP-NeuAc: Galbeta1,3(4)GlcNAc alpha2,3-sialyltransferase (alpha2,3-ST) mRNA was
      expressed in human glioma specimens, human fetal astrocytes, and a panel of brain
      tumor cell lines. Maackia amurensis agglutinin staining revealed the presence of
      alpha2,3-linked sialic acids on glioma cell surfaces and extracellular matrices
      whereas normal human adult astrocytes were negative. Increased expression of
      alpha2,3-linked glycoprotein sialylation may play a role in glial tumorigenesis.

PMID- 9163558
TI  - Effects of 5-HT1A receptor ligands in a modified Geller-Seifter conflict model in
      the rat.
AB  - In a modified Geller-Seifter conflict procedure, rats were trained to lever-press
      for food under a multiple variable interval-fixed ratio (VI30: food; FR10: food +
      shock) schedule of reinforcement. The ability to antagonize response suppression
      in the punished period is considered a good predictor for anxiolytic activity.
      Chlordiazepoxide and alprazolam increased punished responding. The 5-HT1A
      receptor agonists flesinoxan (R(+)-N-[2[4-(2,3-dihydro-2-2-hydroxymethyl-1,4
      benzodioxin-5-yl)- 1-piperazinyl]ethyl]-4-fluorobenzoamide; 0.1-10.0 mg/kg) and 8
      OH-DPAT (8-hydroxy-2-(di-n-propyl-amino)tetralin; 0.03-0.5 mg/kg) significantly
      increased punished responding, supporting a role of the 5-HT1A receptor in
      anxiety. 8-OH-DPAT and flesinoxan also reduced unpunished responding. The
      anxiolytic effects of 8-OH-DPAT and flesinoxan could only be antagonized with a
      high dose (1.0 and 3.0 mg/kg respectively) of the 5-HT1A receptor antagonist WAY
      100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)
      cyclohexanecarboxamide trihydrochloride). All doses of WAY-100635 antagonized the
      5-HT1A-induced effects on unpunished responding. The dissimilarity in dose
      response curve of WAY-100635 on punished and unpunished behaviour poses questions
      about the mediation of these effects.

PMID- 9163559
TI  - Partial role of 5-HT2 and 5-HT3 receptors in the activity of antidepressants in
      the mouse forced swimming test.
AB  - The present study was designed to evaluate the roles of 5-HT2 and 5-HT3 receptors
      in the mouse forced swimming test, by using selective agonists and antagonists of
      5-HT(2A/C) and 5-HT3 receptor sites. Agonists/antagonists and antidepressants
      were administered 45 min and 30 min, respectively, prior to testing. Pretreatment
      with (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI) (4 mg/kg, i.p.) or 2-methyl-5-HT
      (4 mg/kg, i.p.) had no effect on the anti-immobility effects of any
      antidepressant tested. Prior administration of ritanserin (4 mg/kg, i.p.) or
      ketanserin (8 mg/kg, i.p.), on the other hand, potentiated the effects of sub
      active doses of imipramine (8 mg/kg, i.p.) and desipramine (16 mg/kg, i.p.) but
      not of maprotiline (8 mg/kg, i.p.), fluoxetine (16 mg/kg, i.p.), citalopram (16
      mg/kg, i.p.) or fluvoxamine (8 mg/kg, i.p.). Pretreatment with ondansetron (1 X
      10(-5) mg/kg, i.p.) enhanced the antidepressant-like effects of sub-active doses
      of the selective serotonin reuptake inhibitors. The results of the present study
      suggested that, in the forced swimming test, the selective serotonin reuptake
      inhibitors act partially through 5-HT3 receptor sites, whereas the tricyclic
      antidepressants exert effects at 5-HT(2A/C) receptor sites. Anti-immobility
      effects of the selective noradrenaline reuptake inhibitor, maprotiline, do not
      seem to be mediated by 5-HT(2A/C) or 5-HT3 receptor function.

PMID- 9163560
TI  - Talipexole or pramipexole combinations with chloro-APB (SKF 82958) in MPTP
      induced hemiparkinsonian monkeys.
AB  - The effects of two predominant dopamine D2-like receptor agonists, talipexole (6
      allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo [4,5-d]-azepine dihydrochloride, B
      HT 920 CL2) and pramipexole (S(-)2-amino-4,5,6,7-tetrahydro-6-propyl
      aminobenzothiazole dihydrochloride, SND 919 CL2Y), were studied alone and in
      combination with the selective dopamine D1-like receptor agonist chloro-APB ((+/
      )6-chloro-7-8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-benz azepine
      hydrobromide, SKF 82958) in five chronic 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) lesioned hemiparkinsonian Macaca nemestrina monkeys.
      Talipexole induced contraversive rotation in a dose-dependent manner up to 32
      microg/kg, i.m. Talipexole was more potent than pramipexole (10 vs. 32 microg/kg,
      i.m.), but pramipexole was more efficacious in producing contraversive rotational
      behavior and significant hand movements in the afflicted limb. Larger doses of
      chloro-APB also produced contraversive rotation. Combinations of each dopamine D2
      like receptor agonist in a median effective dose with chloro-APB (23.4 and 74.8
      microg/kg, i.m.) had synergistic effects, producing either addition or
      potentiation, depending upon the dose used. The effects noted with these
      combinations were less than the effect of a large dose (100 microg/kg) of
      pramipexole. Talipexole, in the largest dose studied (100 microg/kg, i.m.),
      produced sedation which was not seen with the same dose of pramipexole. No
      significant extrapyramidal side effects were noted with either agent.

PMID- 9163561
TI  - The putative 5-HT1A receptor antagonist DU125530 blocks the discriminative
      stimulus of the 5-HT1A receptor agonist flesinoxan in pigeons.
AB  - Twelve homing pigeons were trained to discriminate the 5-HT1A receptor agonist
      flesinoxan (0.25 mg/kg p.o.) from its vehicle in a fixed ratio (FR) 30 two-key
      operant drug discrimination procedure. Tests for generalization and antagonism
      showed that compounds with agonistic action at the 5-HT1A receptor, such as 8-OH
      DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), buspirone and ipsapirone all
      substituted for the flesinoxan cue. Compounds with mixed agonistic action at the
      5-HT(1A/1B) receptor fully (eltoprazine) or partially (RU24969 (5-methoxy-3
      (1,2,3,6-tetrahydropyridin-4-yl-1H-indole)) substituted for flesinoxan. TFMPP (1
      (3-trifluoromethylphenyl)piperazine) and mCPP (1-(3-chlorophenyl)piperazine),
      both acting at the 5-HT(1B/2C) receptor, did not substitute for flesinoxan,
      neither did the selective 5-HT re-uptake inhibitor fluvoxamine. The results of
      the antagonism tests showed that the 5-HT1A receptor antagonists NAN-190 (1-(2
      methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine), WAY 100635 ((N-[2-[4-(2
      methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclo-he xane-carboxamide) and
      the newly developed DU125530 (2-[4-[4-(7-chloro-2,3-dihydro-1,4-benzodioxin-5-yl)
      1-piperazinyl ]butyl]-1,2-benzisothiazol-3(2H)-one-1,1-dioxide) fully (more than
      80%) blocked the flesinoxan cue without having substantial effects when given
      alone. WAY100135 (N-tert-butyl-3-(4-(2-methoxyphenyl)piperazine-1-yl)-2
      phenylpropanamide ), (+/-)-pindolol and (S)-UH-301 ((S)-5-fluoro-8-hydroxy-2
      (dipropylamino)-tetralin) all partially antagonized the flesinoxan cue. However,
      both WAY100135 as well as (+/-)-pindolol also partially substituted for
      flesinoxan in generalization tests. NAN190, (S)-UH-301, WAY100635 and DU125530
      were without any activity in the generalization test at the doses tested. The
      putative 5-HT1A receptor antagonist S15535 (4-benzodioxan-5-yl) 1-(indan-2
      yl)piperazine) was identified as a full agonist in the present procedure. Taken
      together these results suggest that the flesinoxan cue in pigeons is mediated by
      the 5-HT1A receptor and that DU125530 acts as a full antagonist on the 5-HT1A
      receptor.

PMID- 9163562
TI  - In mononeuropathic rats, the enhancement of morphine antinociception by L
      365,260, a selective CCK(B) receptor antagonist, depends on the dose of systemic
      morphine and stimulus characteristics.
AB  - The ability of the selective cholecystokinin(B) (CCK(B)) receptor antagonist L
      365,260 (0.2 mg/kg s.c.) to modulate the antinociceptive action of relatively low
      doses of systemic morphine (0.1, 0.3 and 1.0 mg/kg i.v.) was evaluated using a
      well established rat model of peripheral unilateral mononeuropathy. Behavioural
      tests based on both mechanical (vocalization threshold to paw pressure) and
      thermal (struggle latency after immersion of the paw into a cold (10 degrees C),
      warm (44 degrees C) or hot (46 degrees C) water bath) stimuli were used.
      Experiments were performed 2 weeks after the surgery when the pain-related
      behaviour has fully developed. We demonstrated a differential effect of L-365,260
      depending both on the dose of morphine and the test used. Pretreatment with the
      CCK(B) receptor antagonist (0.2 mg/kg) inverted the ineffectiveness of the lowest
      dose (0.1 mg/kg i.v.) of morphine against the noxious (46 degrees C) thermal
      stimulus, and the effect of the combination was equal to that seen after the dose
      0.3 mg/kg of morphine alone. Likewise, in the mechanical test, the already
      enhanced effect of this dose (0.1 mg/kg) of morphine on the nerve-injured paw was
      further increased (by 4-fold) after L-365,260 pretreatment. These effects were
      abolished by naloxone (0.01 mg/kg i.v.). However, the effects of the higher doses
      (0.3 and 1.0 mg/kg i.v.) of morphine against the mechanical or noxious thermal
      stimuli were not significantly enhanced by pretreatment with the CCK(B) receptor
      antagonist. Further, L-365,260 was found to be completely ineffective in
      modulating the responses to morphine at 10 degrees C and at 44 degrees C.

PMID- 9163563
TI  - Role of adenosine in the ethanol-induced potentiation of the effects of general
      anesthetics in rats.
AB  - Acetate, derived from ethanol metabolism in the liver, is released into the
      circulation and utilized in many tissues including the brain. The subsequent
      metabolism of acetate results in the production of adenosine that has a number of
      effects in the central nervous system. The purpose of the present studies,
      therefore, was to investigate the contribution of metabolically generated
      adenosine to the ethanol-induced potentiation of the inhalational agents
      isoflurane and sevoflurane. Changes in the anesthetic requirement for isoflurane
      and sevoflurane were determined in rats using the tail-clamp procedure. Both
      ethanol and sodium acetate reduced anesthetic requirement for isoflurane and
      sevoflurane in a dose-dependent fashion. The effect of acetate on anesthetic
      requirement was completely blocked by the administration of the adenosine
      receptor blocker, 8-phenyltheophylline. The ethanol-induced reduction in
      anesthetic requirement, however, was only partially blocked by 8
      phenyltheophylline. Direct intracerebroventricular (i.c.v.) administration of the
      water-soluble adenosine receptor blocker, 8-sulfophenyltheophylline, also
      completely blocked the effect of acetate and partially blocked the effect of
      ethanol. This i.c.v. administration demonstrates that the actions of ethanol and
      acetate on anesthetic requirement are a central nervous system effect. The i.c.v.
      administration of the adenosine A1 receptor subtype agonist, R-phenylisopropyl
      adenosine, potentiated the anesthetic effects of isoflurane and suggests that the
      A receptor mediates the observed potentiation of anesthetic effect. This is
      further supported by the concomitant administration of 5-N-ethylcarboxamido
      adenosine, a non-selective adenosine agonist, with the selective A1 antagonist, 8
      cyclopentyltheophylline, showing A1 receptor potentiation of anesthetic
      requirements. The studies show that (1) acetate potentiates the anesthetic
      effects of the inhalational anesthetics, sevoflurane and isoflurane; (2) acetate
      contributes in part to the effect of ethanol on anesthetic potency through
      metabolically generated adenosine; (3) these effects are likely mediated via
      adenosine A1 receptor subtypes.

PMID- 9163564
TI  - Effect of metrifonate on extracellular brain acetylcholine and object recognition
      in aged rats.
AB  - The effects of metrifonate were investigated in 4-6- and 22-24-month-old rats.
      Extracellular acetylcholine levels were measured by transversal microdialysis in
      vivo. Baseline extracellular acetylcholine levels in the cerebral cortex and
      hippocampus were 42% and 60% lower, respectively, in old than in young rats. Old
      rats did not discriminate between familiar and novel objects. In old rats,
      metrifonate (80 mg/kg p.o.) brought about 85% inhibition of cholinesterase
      activity in the cortex and hippocampus, a 4-fold increase in extracellular
      acetylcholine levels in the cortex only, and restored object recognition. In
      young rats, metrifonate caused 75% cholinesterase inhibition in the cerebral
      cortex and hippocampus, a 2-fold increase in cortical and hippocampal
      extracellular acetylcholine levels, and no effect on object recognition. The
      slight cholinesterase inhibition following metrifonate (30 mg/kg) in aged rats
      had no effect on cortical acetylcholine levels and object recognition. In
      conclusion, metrifonate may improve the age-associated cholinergic hypofunction
      and cognitive impairment.

PMID- 9163566
TI  - Lack of effect of calcitonin gene-related peptide and amylin on major markers of
      glucose metabolism in hepatocytes.
AB  - Effects of amylin and calcitonin gene-related peptide on several processes
      involved in carbohydrate metabolism were investigated in rat hepatocytes, non
      parenchymal cells (Kupffer, Ito and endothelial cells) and alveolar macrophages.
      In hepatocytes, cAMP levels were increased 25-fold by glucagon (10 nM), less than
      2-fold by calcitonin gene-related peptide (100 nM) and not at all by amylin (100
      nM). In non-parenchymal cells and cultured alveolar macrophages, calcitonin gene
      related peptide potently, and amylin weakly, stimulated cAMP levels. In
      hepatocytes neither amylin nor calcitonin gene-related peptide affected glycogen
      phosphorylase activity, glucose output, lactate uptake, glycogen synthesis,
      glycogen mass or tyrosine aminotransferase activity. The density of calcitonin
      gene-related peptide specific binding sites in parenchymal cells was 10-fold less
      then seen in non-parenchymal cells. We found no significant evidence of specific
      amylin binding sites. These results are consistent with the notion that amylin
      does not exert a direct effect in hepatocytes. However, we do not rule out that
      amylin may affect hepatic glucose output indirectly through Cori cycling of
      lactate derived from skeletal muscle or from interactions through non-parenchymal
      cells.

PMID- 9163565
TI  - Rectal response of cardiac origin in the cat: involvement of nitric oxide and
      acetylcholine.
AB  - Local application of nicotine over the surface of the left ventricle and also
      occlusion of the left anterior descending coronary artery in the lightly
      anaesthetised, open-chested, artificially ventilated cat resulted a biphasic
      rectal movement--initial relaxation followed by sustained contraction. However,
      distension of the atrial appendage did not evoke any change in rectal motility,
      indicating the non-involvement of atrial volume receptors in initiating this
      rectal response of cardiac origin. The relaxation phase of this response was not
      abolished by pretreatment with atropine or with phentolamine or propranolol but
      was abolished by the nitric oxide inhibitor, N(G)-nitro-L-arginine (LNNA), and
      this blockade of the relaxation phase by LNNA was reversed by L-arginine. The
      contraction phase, however, was abolished by atropine. From these observations it
      is clear that the relaxation phase of the rectal response to coronary occlusion
      or epicardial nicotine is mediated through neither cholinergic nor adrenergic
      pathways but through the release of nitric oxide whereas the contraction phase of
      such a cardio-rectal response is mediated through the release of the
      neurotransmitter, acetylcholine.

PMID- 9163567
TI  - A local lymph node assay to analyse immunosuppressive effects of topically
      applied drugs.
AB  - Topical glucocorticosteroids represent the mainstay of antiinflammatory therapy
      in the treatment of inflammatory skin diseases. Their clinical use, however, is
      limited by local and systemic side-effects. Thus, in dermatopharmacology there is
      a large demand for alternative non-steroidal antiinflammatories. Other than
      transplantation models, most of the frequently used in vivo test systems for
      assessment of drug-induced immunosuppression measure changes in inflammatory skin
      responses by means of skin erythema and edema after challenge of sensitized
      animals. The aim of this study was to develop an alternative mouse model to
      detect and analyse immunosuppressive effects of topically applied drugs. On the
      basis of a modified local lymph node assay, we analysed effects of topical
      hydrocortisone, dexamethasone, mometasone furoate and FK506 (tacrolimus) during
      the induction phase of contact hypersensitivity. On 4 consecutive days, NMRI mice
      were treated on the dorsal surfaces of both ears with increasing concentrations
      of test compound. During the last 3 days, the mice received in addition the
      contact sensitizer, oxazolone (1%). On day 5, draining auricular lymph nodes were
      removed in order to assess lymph node cell counts and perform flow cytometric
      analysis of lymph node cell subpopulations (CD4+/CD25+, Ia+/CD69+, Ia+/B220+).
      All test compounds proved to exert significant immunosuppressive effects after
      topical application, but showed differences in their immunomodulatory potential.
      In conclusion, the local lymph node assay serves as an appropriate model to
      characterize immunosuppressive effects of topically applied drugs by measuring
      immunologically relevant end-points.

PMID- 9163568
TI  - The effect of 5,8,11,14-eicosatetraynoic acid on endothelial cell gene
      expression.
AB  - The endothelium plays a key role in inflammation, hemostasis and organ rejection.
      We report here that a synthetic polyunsaturated fatty acid, 5,8,11,14
      eicosatetraynoic acid (ETYA), selectively inhibits the up-regulation of several
      genes on endothelial cells. ETYA suppresses endothelial cell activation by
      inhibiting the up-regulation of adhesion molecules like E-selectin. A runoff
      assay for E-selectin demonstrated that the suppression is at the level of
      transcription. The fact that ETYA inhibits E-selectin upon stimulation with a
      diverse group of stimuli like lipopolysaccharide, tumor necrosis factor-alpha or
      phorbol 12-myristate 13-acetate, suggests that ETYA does not exert its effect by
      modifying membrane-bound receptors. The messenger RNA for interleukin-8 and
      glyceraldehyde phosphate dehydrogenase are not affected. Pre-treatment of
      endothelial cells with ETYA also prevents the adherence of monocytes to tumor
      necrosis factor-alpha-stimulated cells.

PMID- 9163569
TI  - Dual effects of auranofin on prostaglandin E2 production by rat peritoneal
      macrophages.
AB  - Incubation of rat peritoneal macrophages in medium containing various
      concentrations of auranofin (1, 3 and 10 microM) increased prostaglandin E2
      production at 4 h in a concentration-dependent manner, in accordance with the
      increase in the release of [3H]arachidonic acid from membrane phospholipids.
      However, at 20 h, no stimulation of prostaglandin E2 production by auranofin was
      observed. When the peritoneal macrophages were incubated in the presence of 12-O
      tetradecanoylphorbol 13-acetate (TPA), thapsigargin or A23187, prostaglandin E2
      production at 4 and 20 h was enhanced. The stimulator-induced prostaglandin E2
      production at 20 h was suppressed by 10 microM of auranofin. Western blot
      analysis demonstrated that auranofin inhibited the induction of cyclooxygenase 2
      by TPA, thapsigargin or A23187 at 4 and 20 h. The level of cyclooxygenase 1 did
      not change by treatment with these stimulators in the presence or absence of
      auranofin. These findings suggest that auranofin has dual effects on
      prostaglandin E2 production: without stimulation, auranofin increases
      prostaglandin E2 production at 4 h due to the increased release of arachidonic
      acid which is converted to prostaglandin E2 mainly by cyclooxygenase 1, but
      inhibits the stimulator-induced late-phase prostaglandin E2 production by
      inhibiting the induction of cyclooxygenase 2.

PMID- 9163570
TI  - Effects of a novel, potent benzothiazepine Ca2+ channel antagonist, DTZ323, on
      guinea-pig ventricular myocytes.
AB  - The effects of a 1,5-benzothiazepine derivative, (+)-cis-3-(acetyloxy)-5-[2-[[2
      (3,4-dimethoxyphenyl)ethyl]-methyla mino]ethyl]-2,3-dihydro-2-(4-methyoxyphenyl)
      1,5-benzothiazepine-4 (5H)-one (DTZ323), on membrane currents were investigated
      in guinea-pig ventricular myocytes using the whole-cell patch-clamp technique.
      DTZ323 suppressed the L-type Ca2+ channel currents (I[Ca(L)]) more selectively
      than the T-type Ca2+ channel and the Na+ channel currents. DTZ323 inhibited
      I[Ca(L)] in a use- and a voltage-dependent manner with 24 times higher potency
      than that of diltiazem. Rate of recovery of I[Ca(L)] from the conditioned block
      by DTZ323 was faster compared with diltiazem and verapamil, and was steeply
      dependent on the holding potential at resting membrane potential range in
      ventricular myocytes (-90 to -60 mV). Our results suggest that DTZ323 is a
      selective Ca2+ channel antagonist, the most potent among the 1,5-benzothiazepine
      Ca2+ channel antagonists, and that the voltage- and use-dependent effect of
      DTZ323 on I[Ca(L)] is due to the steep voltage dependence of the rate of
      dissociation from the cardiac L-type Ca2+ channels.

PMID- 9163571
TI  - Potent inhibition by trivalent cations of ATP-gated channels.
AB  - The effects of La3+ and other trivalent cations on ATP-gated channels (P2X
      purinoceptor/channels) were investigated using rat pheochromocytoma PC12 cells
      and Xenopus oocytes expressing these channels. La3+, Gd3+, Ce3+ and Nd3+ (30-300
      microM) inhibited an inward current activated by 30 microM ATP in PC12 cells. The
      concentration-response curve for the ATP-activated current was shifted by La3+ or
      Gd3+ toward a higher concentration range, and the slope of the curve became
      steeper, suggesting the inhibition is non-competitive. La3+ or Gd3+ did not
      affect the current component that was slowly activated upon hyperpolarization,
      and selectively inhibited the remaining 'voltage-independent' component. La3+ and
      Gd3+ also inhibited currents mediated through P2X1 and P2X2 purinoceptors
      expressed in Xenopus oocytes. The results suggest that La3+ and other trivalent
      cations inhibit P2X purinoceptors at low concentrations. The inhibition may at
      least partly be attributed to an allosteric inhibition.

PMID- 9163572
TI  - Losigamone decreases spontaneous synaptic activity in cultured hippocampal
      neurons.
AB  - Losigamone is a new antiepileptic drug with an unknown mechanism of action. Here
      we report on the effects of losigamone on the synaptic activity in a network of
      cultured rat hippocampal neurons. Losigamone dose dependently reduced the
      frequency of spontaneous synaptic events without affecting the mean current
      amplitude. The drug affected equally the isolated inhibitory as well as
      excitatory postsynaptic currents. Miniature postsynaptic currents were not
      altered by losigamone, suggesting that the mechanism of action depends on
      functional Na+ channels. Consistent with these findings, the drug decreased the
      frequency of spontaneous action potentials and suppressed repetitive firing of
      neurons. Thus, losigamone generally depresses synaptic activity in a neuronal
      network without selectively modulating a specific postsynaptic receptor type. We
      conclude that losigamone acts via a presynaptic mechanism reducing neuronal
      excitability.

PMID- 9163573
TI  - Characterization of the binding and activity of a high affinity,
      pseudoirreversible morpholino tachykinin NK1 receptor antagonist.
AB  - 2(S)-((3,5-Bis(trifluoromethyl)benzyl)-oxy)-3(S)-phenyl-4-((3-oxo-1,2,4- triazol
      5-yl)methyl)morpholine (L-742,694) is a selective morpholino tachykinin NK1
      receptor antagonist that inhibits the binding of 125I-substance P to the human
      tachykinin NK1 receptor with a Kd = 37 pM. Increasing concentrations of L-742,694
      added to cells 15 min prior to agonist progressively increase the apparent EC50
      of substance P for inducing the synthesis of inositol phosphate in Chinese
      hamster ovary (CHO) cells expressing human tachykinin NK1 receptor and decrease
      the maximal level of stimulation observed. In contrast, addition of substance P
      and L-742,694 to the cells at the same time results in an increase in the EC50
      for substance P with no decrease in the maximal level of stimulation. The
      compound also decreases the apparent number of binding sites for 125I-substance P
      observed by Scatchard analysis. Analysis of the binding of [3H]L-742,694 to the
      tachykinin NK1 receptor shows that it associates with the receptor with k(a) =
      3.98 x 10(8) M(-1) min(-1), and dissociates with k(d) = 0.026 min(-1) and t1/2 =
      27 min at 22 degrees C. The slow rate of dissociation of L-742,694 from the
      tachykinin NK1 receptor and the observation that altering the order of addition
      of antagonist and substance P attenuates the effect of the antagonist on the
      maximal activation suggest that L-742,694 is a competitive antagonist that can
      behave as a pseudoirreversible antagonist under some experimental conditions. L
      742,694 has reduced affinity for tachykinin NK1 receptors in which alanine has
      been substituted for Gln165, His197 or His265 in transmembrane helices 4, 5 and
      6, respectively. These three residues have previously been shown to be present in
      the binding site of tachykinin NK1 receptor antagonists of several structural
      classes. In addition, L-742,694 inhibits binding of the quinuclidine antagonist
      (2S,3S)-cis-2-(diphenyl methyl)-N-[(2-iodophenyl)-methyl]-1
      azabicyclo[2.2.2]octane 3-amine ([125I]L-703,606) with the same affinity as it
      inhibits binding of 125I-substance P. These data indicate that L-742,694 binds to
      the same site within the transmembrane domain of the receptor as previously
      described competitive antagonists.

PMID- 9163574
TI  - Antagonist activity of [Thr18,gamma-methylleucine19]endothelin-1 in human
      endothelin receptors.
AB  - Receptor binding and antagonist properties of endothelin-1 analogues,
      [Thr18,gamma-methylleucine19]endothelin-1, [Thr18,Leu19]endothelin-1 and
      [Thr18,cyclohexylalanine19]endothelin-1, were investigated using cloned human
      endothelin ET(A) and ET(B) receptors expressed in Chinese hamster ovary cells.
      Among them, [Thr18,gamma-methylleucine19]endothelin-1 had a high affinity for
      endothelin ET(A) and ET(B) receptors with respective Kd values of 300 and 110 pM
      and had no agonist activity on the stimulation of arachidonic acid release in
      endothelin ET(A) and ET(B) receptor-expressing cells. [Thr18,gamma
      methylleucine19]Endothelin-1 had potent antagonist activity in endothelin-1
      induced arachidonic acid release in endothelin ET(A) and ET(B) receptor
      expressing cells with respective pA2 values of 8.2 and 8.5. In an inositol
      phosphates accumulation assay, [Thr18,gamma-methylleucine19]endothelin-1 also
      exhibited potent antagonist activity for endothelin ET(A) and ET(B) receptors
      with respective pA2 values of 8.0 and 8.4. In conclusion, [Thr18,gamma
      methylleucine19]endothelin-1 acts as a potent and nonselective antagonist with no
      agonist activity for cloned human endothelin ET(A) and ET(B) receptors.

PMID- 9163575
TI  - The depletion of substance P by diclofenac in the mouse.
AB  - Diclofenac in hyaluronan is analgesic and angiostatic. The depletion of substance
      P may be a common mechanism. Mice received diclofenac, diclofenac in hyaluronan,
      or saline i.v. for 5 days and snout substance P assessed: saline 2.80 +/- 0.23;
      0.5 mg/kg diclofenac 2.03 +/- 0.20 (P < 0.05); diclofenac in hyaluronan 1.88 +/-
      0.21 (P < 0.02); capsaicin 1.45 +/- 0.26 fmol/mg tissue (P < 0.005). Substance P
      recovered by 5 days (diclofenac in hyaluronan, capsaicin) and 24 h (diclofenac).
      Diclofenac may deplete substance P in analgesia, and hyaluronan prolong the
      depletion.

PMID- 9163576
TI  - Evidence for a dual function of oxytocin in the control of growth hormone
      secretion in rats.
AB  - The aim of the present study was to investigate the role of oxytocin (Oxy) in the
      control of growth hormone (GH) release. Oxy was administered subcutaneously
      (s.c.) or intracerebroventricularly (i.c.v.) to male rats. The animals were
      decapitated and trunk blood was collected at 30 and 120 min after Oxy
      administration. GH levels were analyzed by radioimmunoassay. Oxy (100 microg,
      s.c) increased plasma levels of GH significantly 30 min after administration. Oxy
      (2 ng, i.c.v.) caused a significant rise of GH after 120 min. This effect was
      completely abolished by previous administration of the Oxy antagonist 1-deamino-2
      D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin. When 5 microg of Oxy were given i.c.v. or 1 mg
      s.c., an inhibition of GH secretion was seen after 120 min. This effect was also
      abolished by the Oxy antagonist. Thus Oxy may influence GH in opposite directions
      depending on the doses given.

PMID- 9163577
TI  - Insulin gene expression in immortalized rat hippocampal and pheochromocytoma-12
      cell lines.
AB  - Employing reverse transcription-polymerase chain reaction and clonal cell lines
      derived by retroviral transduction of the temperature sensitive simian virus 40
      large T-antigen into dispersed rat embryonic hippocampal cells, we detected the
      ancestral gene-insulin II mRNA in three progenitor subcloned cell lines. These
      cell lines upon differentiation are known to express markers indicative of
      commitment to either neuronal (H19-7; NF + , GFAP -), glial (H19-5; GFAP +, NF 
      ), or bipotential (H583-5, NF +, GFAP + ) lineages. No duplicated, i.e., insulin
      I gene expression, was observed in any of the three cell lines. Induction of
      differentiation was associated with the persistence of insulin II mRNA and in the
      cells expressing a neuronal phenotype (H19-7; NF +, GFAP -) a relative doubling
      in insulin II mRNA level was present (P < 0.05). Minimal cellular insulin
      immunoreactivity was detected only in a subpopulation of cells with a
      differentiated neuronal phenotype. Radioimmunoassayable insulin peptide in the
      H19-7 cellular conditioned medium revealed a 5-fold increase in the
      differentiated state. In contrast, peripheral sympathetic PC-12 neuronal cells
      both in the undifferentiated and nerve growth factor-driven differentiated
      states, failed to express both insulin I and insulin II genes. We conclude that
      insulin II is expressed by cultured rat hippocampal clonal cell lines, and not by
      the peripheral sympathetic PC-12 neuronal cell line.

PMID- 9163578
TI  - Influence of endothelin ET(A) and ET(B) receptor antagonists on endothelin
      induced contractions of the guinea pig isolated gall bladder.
AB  - The receptors mediating guinea pig gall bladder (GPGB) contractions induced by
      endothelin-1 (ET-1) and related peptides were characterized using various ET
      receptor antagonists. As all ET-receptor agonists used, except sarafotoxin S6c
      (SRTX), failed to induce a clear-cut maximal response at the highest
      concentration tested (i.e. 100 nM), their potencies are expressed in terms of a
      CK50 (i.e. the concentration causing 50% of the response to 80 mM KCl). ET-1
      (CK50 0.8 nM) was equipotent to ET-2 and SRTX (selective ET(B) receptor agonist),
      but more potent than ET-3 (5-fold) or IRL 1620 (selective ET(B) receptor
      agonist). BQ-123 (0.3 microM, peptidic ET(A) receptor antagonist) did not alter
      responses to ET-1, ET-3 or SRTX. BQ-788 (1 microM, peptidic ET(B) receptor
      antagonist) reduced the potency of ET-3 (9-fold at the CK50 level) and SRTX ( >
      20-fold), but not ET-1. SRTX responses were unaffected by RES-701-1 (3 microM,
      peptidic ET(B) receptor antagonist). The combination BQ-123 (0.3 microM) plus BQ
      788 (1 microM) did not modify responses to ET-1, inhibited SRTX responses
      similarly to BQ-788 alone and abolished ET-3 responses. Bosentan (1 microM, non
      peptidic ET(A)/ET(B) receptor antagonist) reduced the potency of ET-1 (15-fold).
      ET-3 (9-fold) and SRTX (4-fold). In rat aorta, the antagonists blocked ET-1
      induced contractions (BQ-123 and bosentan) or SRTX-induced endothelium-dependent
      relaxations (BQ-788, RES-701-1 and bosentan). Thus, the GPGB expresses both ET(A)
      and ET(B) receptors. As BQ-123 only blocked responses to ET-3 in the presence of
      BQ-788, there appears to be cross-talk between both receptor types. Also, the
      binding sites of ET-1 and ET-3 on the ET(A) receptor may not coincide entirely,
      as BQ-123, even in presence of BQ-788, did not affect ET-1-induced contractions.

PMID- 9163579
TI  - Quantification of Locusta diuretic hormone in the central nervous system and
      corpora cardiaca: influence of age and feeding status, and mechanism of release.
AB  - Locusta-DH is known to have a hormonal function in the control of post-feeding
      diuresis in the migratory locust. This study has quantified Locusta-DH in tissues
      from V(th) instar nymphs and adults, and investigated the K+-induced release of
      the peptide from corpora cardiaca. Locusta-DH is present in thoracic and
      abdominal ganglia, but the amounts are small (25-200 fmol) compared with brain
      (approximately 1 pmol) and corpora cardiaca ( > 5 pmol) from 14-day old locusts.
      About 50% of the immunoreactive material in corpora cardiaca coelutes with
      Locusta-DH on reversed-phase HPLC. An earlier eluting fraction is also
      biologically active, suggesting locusts have a second, previously undetected, CRF
      related peptide. The amount of peptide stored in corpora cardiaca varies with age
      and physiological status. Reductions on day 1 of the adult instar and immediately
      after feeding suggest Locusta-DH controls post-eclosion as well as post-feeding
      diureses. Locusta-DH is released by a Ca2+-dependent mechanism from corpora
      cardiaca held in salines containing > or =40 mM K+. This is blocked by verapamil,
      implicating L-type Ca2+ channels. Release is most rapid shortly after transfer to
      a high K+ saline, and more peptide is released from glands allowed to recover in
      normal saline between successive K+ depolarisations.

PMID- 9163581
TI  - Characterization of an insulin-like growth factor (IGF) receptor and the insulin
      like effects of IGF-1 in the bony fish, Lates calcarifer.
AB  - The present work is part of a broad phylogenetic study of the insulin superfamily
      of peptides in lower vertebrates. In the bony fish barramundi (Lates calcarifer),
      the presence of IGF receptors were investigated in the liver by means of
      competitive binding studies. The results suggested the presence of a type 1-like
      but no type 2-like IGF receptor. We also demonstrated insulin-like effects of
      intraperitoneally injected recombinant human (rh)-IGF-1 in barramundi with rh-IGF
      1 and rh-insulin showing similar effects with respect to induction of
      hypoglycemia and stimulation of incorporation of [14C]-glucose into muscle
      glycogen.

PMID- 9163580
TI  - Role of vagal fibers and bombesin/gastrin-releasing peptide-neurons in distention
      induced gastrin release in rats.
AB  - In the rat the exact role of vagal fibers and the interaction between the
      extrinsic and intrinsic neural system in distention-induced gastrin release are
      still a matter of debate. Accordingly, the aim of the present study was to
      examine the contribution of afferent and efferent vagal fibers as well as
      intrinsic neurons on gastrin response to gastric distention. In anesthetized rats
      graded gastric distention by 5, 10 and 15 ml saline for 20 min caused a
      significant volume-dependent increase of plasma gastrin levels by 12+/-6 pg/ml (5
      ml saline, n = 8, P =0.05), 26+/-7 pg/ml (10 ml saline, n = 10, P < 0.05) and
      37+/-7 pg/ml (15 ml saline, n = 8, P < 0.01 ), respectively. To examine the role
      of the extrinsic vagal innervation, gastrin response to distention was studied in
      anesthetized rats after bilateral truncal vagotomy (n = 9) or selective afferent
      vagotomy following pretreatment with capsaicin (n = 6). Stimulation of gastrin
      release by 10 ml distention in sham-operated control rats was reversed to an
      inhibition after truncal vagotomy (26+/-7 vs. -11+/-4 pg/ml; P<0.05) and
      capsaicin-treatment (37+/-18 vs. -34+/-11 pg/ml; P<0.05). A contribution of
      cholinergic mechanisms to this vagovagal-mediated stimulation of distention
      induced gastrin release was excluded, since atropine (100 microg/kg/h; n = 8)
      further augmented distention-stimulated gastrin release. Since bombesin/gastrin
      releasing peptide (GRP)-neurons contribute to vagally stimulated gastrin
      secretion, we have examined gastrin response to distention in the presence of the
      specific bombesin-receptor antagonist D-Phe6-BN(6-13)OMe (400 microg/kg/h: n =
      10). This bombesin-antagonist completely reduced distention-stimulated gastrin
      release in vivo. In contrast, distention of the isolated, extrinsically
      denervated stomach significantly decreased gastrin release by 13+/-5 pg/min (5 ml
      saline, n = 8, P < 0.05), 28+/-8 pg/min (10 ml saline, n = 11, P < 0.05) and 35+/
      10 pg/min (15 ml saline, n = 8, P < 0.01), respectively, without changing the
      activity of bombesin/GRP-neurons. Distention-induced decrease of gastrin release
      was attenuated to 50 percent by atropine (10(-7) M: n = 10) or tetrodotoxin (TTX)
      (10(-6) M; n = 10), respectively. These data demonstrate, that in anesthetized
      rats distention-stimulated gastrin secretion depends on the activation of a
      vagovagal reflex and intrinsic bombesin/GRP-neurons. In contrast distention of
      the isolated rat stomach inhibits gastrin release in part via intrinsic
      cholinergic pathways and other as yet unknown mechanisms.

PMID- 9163582
TI  - Nitric oxide is involved in the inhibitory action of cholecystokinin octapeptide
      (CCK-OP) on proximal colonic motility.
AB  - To determine whether nitric oxide (NO) is a possible mediator in the inhibitory
      action of CCK-octapeptide (CCK-OP) on circular muscle contractions of the rat
      proximal colon, contractile activities of the circular muscle were recorded in
      the proximal colon of unrestrained conscious rats in the fasting state using a
      miniature strain gauge force transducer and an implantable telemetry system.
      Regular and rhythmic phasic contractions were observed during the fasted
      condition, similar to the myoelectric migrating complex seen in intestinal
      contractions of the fasting dog. These phasic contractions were almost completely
      inhibited after intraperitoneal (i.p.) administration of CCK-OP at a dose of 15
      microg/kg body weight. N(omega)-nitro-arginine, methyl ester (L-NAME), at doses
      of 20 and 200 mg/kg i.p. administered prior to i.p. injection of CCK-OP,
      prevented the inhibitory action on the fasting phasic contractions. The degree of
      prevention was dose-dependent. 100 mg/kg body weight i.p. injection of L-arginine
      inhibited the circular muscle contractions. The same dose of D-arginine had no
      action on contractions of the circular muscle of the proximal colon in the fasted
      rat. From these data, we conclude that NO is one possible mediator in the
      inhibitory mechanism of CCK-OP on smooth muscle motor activity of the rat
      proximal colon in vivo.

PMID- 9163583
TI  - Chronic transfusion programmes in sickle cell disease: problem or panacea?

PMID- 9163584
TI  - Automated red cell exchange in sickle cell disease.
AB  - Red cell exchange is important in the care of acutely ill sickle-cell patients,
      and may be life-saving. An automated red cell exchange technique has been
      developed using a Baxter blood cell separator, enabling an isovolaemic exchange
      to be performed within 2.5 h. A total of 20 procedures have been performed in 15
      patients, including one woman in the third trimester of pregnancy, with a mean
      decrease of 72% in the circulating sickle haemoglobin (HbS) level. This method
      enables almost all adult patients with sickle cell anaemia to have their HbS
      reduced to safe levels by only one procedure. The procedure was well tolerated by
      all patients, including those who were acutely ill. This technique provides an
      effective procedure for reducing the percentage of circulating HbS rapidly in
      acutely ill patients with complications of sickle cell anaemia.

PMID- 9163585
TI  - HbC compound heterozygotes [HbC/Hb Riyadh and HbC/Hb N-Baltimore] with opposing
      effects upon HbC crystallization.
AB  - Compound heterozygotes of variant haemoglobins (Hbs) with HbC, with or without
      novel phenotypic changes, have provided insight into the molecular basis of the
      interacting haemoglobins and information concerning the role of specific residues
      in the crystallization of oxy HbC. A high phosphate buffer system has proved
      useful for studying the effects of variant haemoglobins (naturally co-existing
      with HbC in the red cell) on the oxy HbC crystallization process and has led us
      to conclude that beta87 and beta73 are contact sites of the oxy HbC crystal. We
      now present investigations from two HbC compound heterozygotes which exhibit
      opposing effects upon HbC crystallization: HbC/Hb N-Baltimore (beta95 Lys-->Glu)
      and HbC/Hb Riyadh (beta120 Lys-->Asn). The latter inhibits the in vitro
      crystallization of HbC, explaining the lack of erythrocyte abnormalities (with
      the exception of microcytosis) in the doubly heterozygous infant. In contrast, Hb
      N-Baltimore accelerates the crystallization of HbC, contributing to multiple
      abnormalities in red cell morphology, albeit in the absence of morbidity. We
      conclude that (1) beta120 and beta95 are additional contact sites in the crystal,
      and (2) the HbC/Hb Riyadh haemoglobinopathy demonstrates that crystallization may
      not be required for the generation of the observed microcytosis and increased red
      cell density in HbC-containing red cells.

PMID- 9163586
TI  - Beta-thalassaemia in the immigrant and non-immigrant German populations.
AB  - In Germany homozygous beta-thalassaemia mainly occurs in the immigrant population
      from endemic regions. In non-immigrants beta-thalassaemia is rare. Heterozygous
      beta-thalassaemia minor, however, is more common and must be considered in the
      differential diagnosis of hypochromic anaemia. The clinical and molecular data of
      221 homozygous patients and 256 non-immigrant German heterozygous individuals are
      presented. Clinically, 87% (n = 192) of the homozygotes are classified as
      thalassaemia major (TM) and the other 13% as thalassaemia intermedia (TI). There
      is a wide spectrum of 39 thalassaemia mutations which occur with relatively low
      frequencies in individual cases. In 17/29 TI patients 'mild' mutations have been
      found and in 16/29 there are mutations that are associated with increased gamma
      globin gene activity. alpha-Thalassaemia is rare and found only in 3/29. In the
      256 Germans with heterozygous beta-thalassaemia there are 27 different
      thalassaemia mutations. The three most common are Mediterranean, together
      accounting for 61%. Also relatively common (5%) is an otherwise rare frameshift
      mutation of codon 83 (FS83 deltaG). The other mutations occur in < 10
      individuals. Two mutations described here are novel. One of them affects position
      -2 of the intron 1 splice acceptor site (IVSI-129 A-G) and the other is a
      deletion of a single G in codon 15/16 (FS 15/16 deltaG). These data suggest that
      beta-thalassaemia in Germans was introduced from the Mediterranean in about two
      thirds of cases and that the remaining third has probably originated locally.

PMID- 9163587
TI  - Spectrin Cosenza: a novel beta chain variant associated with Sp alphaI/74
      hereditary elliptocytosis.
AB  - A Calabrian family (Southern Italy) with Sp alpha(I/74) hereditary elliptocytosis
      (HE) in the heterozygous state was studied. Sp alpha(I/74) HE is associated with
      asymptomatic elliptocytosis, a defect in spectrin dimer self association and an
      increase of the alpha(I/74) kD fragment from the alpha chain after partial
      tryptic digestion of spectrin. To identify the underlying molecular defect, we
      analysed exons V, W, X, Y, Z of the beta gene and exon 2 of the alpha gene by
      single-strand conformational polymorphism (SSCP) of the amplification products.
      Direct DNA sequencing of the mutant exon showed a C-->G substitution at position
      6284 of the beta gene. The corresponding substitution at the protein level was
      Arg-->Pro in the 2064 position of the beta-spectrin chain.

PMID- 9163588
TI  - A novel form of hereditary sideroblastic anaemia with macrocytosis.
AB  - We describe a pedigree with maternally inherited sideroblastic anaemia in which
      the red cells are dimorphic with a raised MCV. To our knowledge, this form of
      hereditary sideroblastic anaemia (HSA) has not been reported previously. 16
      members of the family were investigated, revealing eight affected members. Two
      further family members were not tested but were presumed affected on the
      histories available. The proband, born in 1967, presented during pregnancy with a
      macrocytic anaemia (Hb 7.0 g/dl, MCV 106 fl) and a dimorphic red cell picture.
      Post partum, a bone marrow biopsy showed hypercellularity, mild dyserythropoiesis
      and ring sideroblasts. Cytogenetics were normal. Other causes of macrocytosis
      were excluded. Six other family members (three female, three male) have similar
      findings. There is no evidence of paternal transmission. An additional female
      relative who presented in 1992 with refractory anaemia with excess blasts in
      transformation and a dimorphic blood film, died from progression to AML. Affected
      members show a raised metal-free red cell protoporphyrin level suggestive of a
      defect at the level of Fe2+ incorporation into protoporphyrin. We propose that
      this form of HSA is due to a mitochondrial mutation. A search for deletions or
      point mutations in the mitochondrial DNA is currently underway.

PMID- 9163589
TI  - PIG-A gene mutations in four Taiwanese patients with paroxysmal nocturnal
      haemoglobinuria following aplastic anaemia.
AB  - Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired haemolytic disorder
      caused by deficient biosynthesis of the glycosyl phosphatidylinositol (GPI)
      anchor in haemopoietic stem cells. PIG-A, an X-linked gene that participates in
      the first step of GPI-anchor synthesis, is responsible for PNH. Various
      abnormalities of the PIG-A gene have been demonstrated in all patients with PNH
      so far examined. In this study we characterized the somatic mutations in PIG-A
      gene in four Taiwanese patients with PNH. We identified five novel mutations in
      the PIG-A gene, three single nucleotide substitution mutations (-342, C-->G,
      codon 335, GGT-->AGT and codon 405, GCT-->GTT) and two frameshift mutations
      (codon 22, GGA-->G-A and codon 356, TGT-->TGTT) in the PIG-A gene. The -342
      mutation was judged to be a polymorphism. Furthermore, three patients had
      previous clinicopathologic evidence which suggested aplastic anaemia (AA), before
      the development of PNH. One of these was found to have thrombocytopenia during
      follow-up. We suggest that the somatic PIG-A gene mutations highlight a subgroup
      of AA having a pathogenetic link with PNH.

PMID- 9163590
TI  - Heart transplantation for end-stage heart failure caused by iron overload.
AB  - Few reports exist concerning heart transplantation in recipients with end-stage
      myocardiopathy-associated heart failure caused by iron overload occurring with
      beta-thalassaemia, Diamond-Blackfan syndrome or haemochromatosis. Seven potential
      transplant candidates (six male, one female, mean age 26 years) with such heart
      failure, following desferrioxamine application subcutaneously over a number of
      years, and intravenously during their hospitalization before transplantation,
      were retrospectively analysed. Five were New York Heart Association (NYHA) class
      IV, three experienced one or more resuscitations immediately before
      transplantation could be performed. Continuous, high-volume, veno-venous
      haemofiltration was necessary in two patients. One of these two candidates
      additionally had to be bridged, first with a right ventricular, then with a
      biventricular assist device. Five of the seven patients survived, two with
      haemochromatosis, one with beta-thalassaemia major and one with Diamond-Blackfan
      syndrome following transplantation. One non-transplanted candidate with beta
      thalassaemia major has been recompensated for 5 years. Survival was 14-74 months.
      Our results demonstrate the feasibility and indication of transplantation in
      patients with such heart failure and the satisfying outcome of immunosuppression
      is described.

PMID- 9163591
TI  - Anaemia of lung cancer is due to impaired erythroid marrow response to
      erythropoietin stimulation as well as relative inadequacy of erythropoietin
      production.
AB  - Many studies have been done in order to elucidate the pathogenesis of the anaemia
      of chronic disorders accompanying cancer, with conflicting results. This is
      probably due to the heterogeneity of the patient population selected for these
      studies (many patients treated by chemotherapy). To avoid this pitfall, in this
      study a very homogenous group of chemotherapy and radiotherapy-naive patients
      with lung cancer were selected. Serum erythropoietin and soluble transferrin
      receptor measurements suggested that the anaemia of non-treated lung cancer is
      mainly due to an impaired erythroid marrow response to erythropoietin
      stimulation. However, a relative inadequacy of erythropoietin production may also
      contribute.

PMID- 9163592
TI  - Effects of all-trans-retinoic acid on superoxide generation in intact neutrophils
      and a cell-free system.
AB  - To determine the pathophysiology of the retinoic acid syndrome which occurs
      during all-trans-retinoic acid (ATRA) treatment of acute promyelocytic leukaemia
      patients, we investigated the direct effects of ATRA on the function of human
      neutrophils. We found that ATRA (10-200 microM) dose-dependently stimulated
      superoxide (O2-) generation in intact neutrophils. The maximal activity of ATRA
      stimulated O2- generation was 3.0 nmol/min/10(6) cells. Adding EGTA to the assay
      mixture did not affect the activity nor was the intracellular free calcium
      concentration changed upon stimulation. The treatment of neutrophils with 0.1
      microM staurosporine, an antagonist of protein kinase C, for 10 min, enhanced the
      activity of ATRA-stimulated O2- generation up to 186% of that for control
      samples. Wortmannin (1 microM), an inhibitor of phosphatidylinositol 3-kinase (PI
      3-kinase), reduced this stimulatory activity by 67%. These results suggest that
      ATRA activates the signalling pathway related to PI 3-kinase rather than that
      utilizing calcium and protein kinase C. ATRA enhanced the O2- generated in a
      sodium-dodecyl-sulphate (SDS) cell-free system, resulting in rates up to 288%
      higher than that seen with SDS alone. This enhancement was not affected by
      pretreatment with staurosporine or wortmannin. ATRA may thus directly activate
      and/or enhance the function of neutrophils.

PMID- 9163593
TI  - Sustained remission of severe resistant autoimmune neutropenia with Campath-1H.
AB  - We report the course of a patient with severe autoimmune neutropenia in whom only
      transient responses occurred with corticosteroids, antilymphocyte globulin and
      granulocyte-colony stimulating factor, and who was resistant to treatment with
      azathioprine, cyclosporin and intravenous immunoglobulin. A 10 d course of
      intravenous Campath-1H monoclonal resulted in a sustained haematological
      response. The long-lasting effect of Campath-1H may be due to its remarkable
      ability to induce a profound and prolonged peripheral blood T lymphopenia.

PMID- 9163594
TI  - Treatment of dyskeratosis congenita with granulocyte colony-stimulating factor
      and erythropoietin.
AB  - Aplastic anaemia is both frequent and difficult to manage in patients with
      dyskeratosis congenita (DC). We recently treated a 23-year-old male for a year
      with granulocyte colony-stimulating factor (G-CSF) and erythropoietin (Ep), with
      an excellent neutrophil response, and a transient effect on haemoglobin levels. G
      CSF alone or combined with other cytokines may provide at least a partial effect
      in pancytopenic patients with DC.

PMID- 9163595
TI  - A phenylalanine-55 to serine amino-acid substitution in the human glycoprotein IX
      leucine-rich repeat is associated with Bernard-Soulier syndrome.
AB  - The platelet membrane glycoprotein (GP) Ib-IX-V complex, the major von Willebrand
      factor receptor on platelets, is absent or dysfunctional in patients with the
      Bernard-Soulier syndrome (BSS). The four single subunits of the GPIb-IX-V complex
      (GPIb alpha, Ib beta, IX and V) are molecular products of different genes.
      Several point mutations and deletions affecting the GPIb alpha gene have been
      identified as the cause of BSS, whilst in four BSS families a GPIX gene defect
      has been reported. Moreover, a single case of BSS has been associated with a
      genetic defect of GPIb beta. We investigated the molecular basis of another case
      of BSS with a deficient expression of GPIX, as detected by immunofluorescence
      studies. After amplification of the entire GPIX coding region, nucleotide
      sequence analysis showed a homozygous single point mutation predicting a
      phenylalanine to serine substitution at position 55 of the mature GPIX within its
      unique leucine-rich repeat. By allele-specific oligonucleotide hybridization we
      confirmed the homozygosity of the patient as well as the carrier state of two out
      of three of his children studied. Although the parents of the patient, who were
      first cousins, were no longer alive and thus not available for study, we
      speculate that the molecular defect observed in the proband was inherited from
      both parents, who probably were heterozygous for this GPIX gene defect. This
      study confirms that BSS may be caused by many different subtle molecular defects
      that often prevent the assembly and expression of a functional GPIb-IX-V complex.

PMID- 9163596
TI  - Platelet activation by a novel solid-phase agonist: effects of VWF immobilized on
      polystyrene beads.
AB  - The interaction between platelets stirred in suspension and VWF immobilized on
      polystyrene beads was studied. Platelets aggregated and released ATP in response
      to stirring with VWF beads. Closer examination of the interaction using
      transmission electron microscopy revealed that the platelets did not simply
      aggregate with one another but initially adhered to the beads and spread.
      Platelets in suspension then bound to the bead-adherent platelets forming layers
      of platelets associated with each bead. The VWF bead-induced platelet activation
      was completely inhibited by addition of monoclonal antibody (mAb) to GPIb or
      GPIIb/IIIa. In addition, the activation response was inhibited in the presence of
      aspirin, indomethacin or the thromboxane receptor antagonist BM13.177,
      demonstrating a dependence on an intact cyclo-oxygenase pathway. Platelet
      function studies were carried out on 30 patients with a history of mild bleeding
      using conventional optical aggregation and VWF bead-induced platelet activation.
      12 patients were abnormal by conventional optical aggregometry, whereas 27
      patients showed depressed ATP release in response to VWF beads. The results
      suggest that easily-bruised patients may have a platelet function defect rather
      than a vascular-based abnormality and that VWF bead-induced platelet activation
      is a more sensitive test for detecting platelet dysfunction.

PMID- 9163597
TI  - The Arg633His substitution responsible for the private platelet antigen Gro(a)
      unravelled by SSCP analysis and direct sequencing.
AB  - We have previously described the private or family platelet antigen, Gro(a),
      which was identified in a case of neonatal alloimmune thrombocytopenia. The
      Gro(a) antigen was found to be located on the GP IIIa (beta3) subunit of the GP
      IIb/IIIa complex, the most prominent fibrinogen receptor of platelets. Initial
      experiments to characterize the Gro(a) antigen at the molecular genetic level
      were unsuccessful. We therefore decided to use a different strategy to unravel
      the molecular basis of this antigen. Platelet GP IIIa mRNA of a Gro(a+) and a
      Gro(a-) donor was amplified with suitable primers in a reverse transcriptase
      polymerase chain reaction (RT-PCR) and subjected to single-strand conformational
      polymorphism (SSCP) analysis. Three regions of the amplified GP IIIa cDNA derived
      from the Gro(a+) donor showed a different SSCP pattern when compared to that of
      the Gro(a-) donor. Direct nucleotide sequence analysis of these three segments
      revealed that two of them contained silent substitutions, A1163C, A1553G and
      G1565A. The first and the latter changes were described previously. In the third
      segment a G1996A mutation was found, predicting an arginine --> histidine
      substitution at position 633 of the mature glycoprotein. PCR-ASRA (allele
      specific restriction enzyme analysis) performed on cDNA as well as on genomic DNA
      with the restriction enzyme MaeIII showed that the His633 form of GPIIIa is
      restricted to the Gro(a+) phenotype. The observed mutation is three amino acids
      upstream of the mutation underlying the HPA-8/Sr system (Arg636Cys), suggesting
      this region of GP IIIa to be susceptible for mutations. Moreover, the presence of
      a silent mutation and two low-frequency forms of the silent polymorphisms
      strongly suggests that the G1996A mutation did not occur in a direct ancestral
      allele.

PMID- 9163598
TI  - Dapsone for chronic autoimmune thrombocytopenic purpura: a report of 66 cases.
AB  - Sixty-six adults with chronic autoimmune thrombocytopenic purpura AITP and
      platelet count <50 x 10(9)/l were treated with dapsone (75-100 mg orally). A
      response was observed in 33 patients. The median duration of treatment required
      to obtain a response was 21 d (range 8-90). The median maximal platelet count on
      treatment was 130 x 10(9)/l (range 71-355). Dapsone was continued in 20/33
      responders for a median of 12.5 months (range 1-48) and the response persisted in
      19. Treatment was intentionally withdrawn in the other 13 responders and
      thrombocytopenia immediately recurred in 12. Reversible side-effects required
      cessation of treatment in seven patients. These results demonstrate that dapsone
      is an effective, inexpensive, and well-tolerated treatment for chronic AITP.

PMID- 9163599
TI  - Interferon increases serum thrombopoietin in patients with chronic hepatitis C.
AB  - We measured serum thrombopoietin (TPO) in chronic hepatitis C treated with
      interferon (IFN). The platelet count before the therapy was 161.9 x 10(9) +/-
      64.1 x 10(9)/l, which decreased to 116.3 x 10(9) +/- 48.4 x 10(9)/l 1 week after
      IFN therapy (P < 0.01). On the other hand, serum TPO increased from 1.96 +/- 0.60
      fmol/ml to 2.68 +/- 0.69 fmol/ml (P < 0.02). Contrary to a recent report that
      serum TPO was not altered in liver cirrhosis, these data indicate that serum TPO
      was increased in chronic hepatitis C in response to thrombocytopenia by IFN
      therapy.

PMID- 9163600
TI  - The role for liver biopsy in haemophiliacs infected with the hepatitis C virus.
AB  - Assessment of chronic hepatitis C virus infection requires a liver biopsy in most
      circumstances. There is a reluctance to perform liver biopsy in haemophiliacs
      because of a perceived risk of haemorrhage, although with adequate factor
      concentrate replacement in patients without factor concentrate inhibitors it
      should be safe. We report a 4-year experience of liver biopsy in patients with
      haemophilia infected with chronic hepatitis C virus. Of 55 patients seropositive
      for anti-HCV, 35 have undergone liver biopsy; the median age of this group was 33
      years (range 13-68). Seven patients had a normal liver. 22 had portal tract
      inflammation, four with lymphoid aggregates. Mild piece-meal necrosis was
      observed in only two and no bile duct injury was found. 11 patients had mild
      mixed micro- and macro-vesicular fat. 19 patients had no evidence of fibrosis
      despite an estimated median duration of disease of 20 years (range 8-43). In the
      remaining 16 patients the maximum degree of fibrosis achieved was stage III.
      Patients with more significant fibrosis could not be identified on the basis of
      ALT or HCV RNA. There were no complications of liver biopsy in this series. Liver
      biopsy following a well-defined protocol in chronic hepatitis C virus
      haemophiliac carriers is safe in the absence of factor concentrate inhibitors. In
      this young group of patients without HIV infection there was no evidence of
      significant liver disease despite a considerable duration of disease. Performing
      liver biopsy allows accurate information to be given to the patient and avoids
      unnecessary therapy. The relative youth of this group may be important in the
      light of the benign histology.

PMID- 9163601
TI  - Re-expression of functional P-selectin molecules on the endothelial cell surface
      by repeated stimulation with thrombin.
AB  - P-selectin (GMP-140, PADGEM, CD62P) is a cell adhesion receptor which is believed
      to play an important role in inflammatory diseases by supporting leucocyte
      rolling. P-selectin is located on the granule membrane of Weibel-Palade bodies in
      resting endothelial cells and is expressed on the cell surface during cellular
      activation with various stimulators such as thrombin. Thereafter, P-selectin is
      internalized and sorted to the Golgi region and Weibel-Palade bodies again.
      However, whether P-selectin is re-expressed upon subsequent cellular stimulation
      has, to date, been unclear. To address this question, we measured the cellular
      content and surface expression of P-selectin, using indirect immunofluorescence
      and confocal laser cytometry. Surface expression of P-selectin reached a maximum
      < 2 min after thrombin stimulation and declined to basal levels after 180 min.
      Rechallenge with thrombin induced rapid surface re-expression of P-selectin,
      which was independent of de novo protein synthesis, since cycloheximide did not
      inhibit re-expression. Moreover, re-expressed P-selectin supported the adherence
      of HL60 promyelocytic cells. These results clearly demonstrated that functional P
      selectin molecule was recycled after repeated stimulation with thrombin, raising
      the possibility that P-selectin is involved in chronic inflammation.

PMID- 9163602
TI  - Expression and modulation of cellular receptors for interferon-gamma, tumour
      necrosis factor, and Fas on human bone marrow CD34+ cells.
AB  - Interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and Fas
      ligand can mediate potent inhibitory signals in haemopoietic cells. Clinical and
      laboratory studies have suggested the involvement of these cytokines in the
      regulation of normal haemopoiesis and in the pathophysiology of bone marrow (BM)
      failure syndromes. As the effects of cytokines may also be regulated at the
      cellular receptor level, we studied the expression and modulation of TNF receptor
      (TNFR), IFN-gammaR and Fas-R on haemopoietic progenitor cells. In freshly
      isolated BM, using flow cytometry, TNFR1 (p55), TNFR2 (p75), IFN-gammaR, and Fas
      R were detected on 5-12% of mononuclear cells. Two-colour staining showed
      comparable receptor expression on a CD34+ population, which includes haemopoietic
      progenitor and stem cells. Using reverse transcriptase-PCR (RT-PCR) transcription
      of mRNA coding for these receptors was demonstrated in fresh, highly purified
      CD34+ cells. These findings indicate that the effects of these factors on
      progenitor cells may be directly mediated. In cultured BM cells, expression of
      TNFR1 was not influenced by IFN-gamma, TNF-alpha or apoptosis-inducing anti-Fas
      monoclonal antibody (mAb). IFN-gamma decreased CD34+ cell TNFR2 expression. CD34+
      cell Fas-R expression was increased by IFN-gamma and TNF-alpha. IFN-gammaR
      expression was enhanced by anti-Fas mAb and to lesser degree with TNF-alpha.
      Similar results were obtained with RT-PCR analysis in cultured CD34+ cells.
      Potentiation of anti-Fas mAb-mediated inhibition of haemopoietic colony formation
      by IFN-gamma and TNF-alpha was observed. Similarly, anti-Fas mAb enhanced the
      inhibitory effects of IFN-gamma. These results suggest that, in addition to
      interacting at the level of intracellular signalling pathways, IFN-gamma, TNF
      alpha or Fas-ligand may potentiate or antagonize their effects through modulation
      of cytokine receptor expression.

PMID- 9163603
TI  - Molecular basis of the D variant phenotypes DNU and DII allows localization of
      critical amino acids required for expression of Rh D epitopes epD3, 4 and 9 to
      the sixth external domain of the Rh D protein.
AB  - The discovery of Rh partial D variant red cells by discrepant reactions with
      different monoclonal anti-D has demonstrated the range of Rh D epitopes that have
      arisen due to alterations in Rh D protein structure. There are two current
      classification systems, one which uses a nine epitope model (epD1-epD9) whereas a
      more recent model proposes 30 different epitopes. We describe here the molecular
      basis of two D variants which lack epD4 and epD9 namely the DNU and D(II)
      phenotypes. These would have both been originally classified as D(II) phenotype
      individuals, but we have revealed subtle differences in the serological profile
      of these erythrocytes. Such a differential reactivity and determination of the
      molecular bases of these phenotypes allows us to predict critical amino acids for
      epD3, epD4 and epD9 expression. The DNU phenotype arises from a single point
      mutation in the RHD gene resulting in a single amino acid change (Gly353Arg).
      Sequence analysis of exon 7 of the RHD gene derived from the D(II) propositus
      indicates that there is a single point mutation in this exon resulting in a
      single amino acid change (Ala354Asp). It is likely that this point mutation gives
      rise to the D(II) phenotype. Both mutations result in the change to Rh D-specific
      residues. Our results indicate that the following amino acids are crucial for
      epD3a (Asp350), epD3b (Asp350 + Gly353), epD4a (Gly353 + Ala354), epD4b (Ala354),
      epD9a (Asp350 + Gly353 + Ala354) and epD9b (Asp350 + Ala354) expression. All of
      these amino acids reside on the predicted sixth external domain of the Rh D
      protein, so it is possible that epD3, 4 and 9 are continuous epitopes.

PMID- 9163604
TI  - Morphological and cytochemical findings in 150 cases of T-lineage acute
      lymphoblastic leukaemia in adults. German Multicentre ALL Study Group (GMALL).
AB  - We evaluated the morphological findings in 150 consecutive cases of T-lineage
      acute lymphocytic leukaemia (T-ALL). Cytochemistry including PAS staining and
      acid phosphatase reaction proved of limited value for the diagnosis of ALL. The
      diagnosis of acute leukaemia was easy to establish in most instances. However, in
      a few cases the leukaemic cells were difficult to recognize as blasts. The nuclei
      of such cells showed condensed chromatin and nucleoli were lacking, and was
      encountered particularly in thymic ALL. Basophilic cytoplasm combined with
      prominent vacuolization suggestive of mature B-ALL (ALL-L3 type), was observed in
      16 cases. Other features, however, such as cell size, polymorphism, chromatin
      structure, sparse cytoplasm or focal positivity for acid phosphatase, excluded a
      diagnosis of ALL-L3 in those cases. Distinction from hybrid leukaemia was
      difficult in 20 cases, because of a low percentage of peroxidase-positive blasts
      or other features which suggested a separate myeloid leukaemia component. In nine
      of these the hybrid nature of the leukaemia was considered as certain on the
      basis of morphology. Seven cases had been diagnosed as biphenotypic with
      coexpression of myeloid and lymphoid markers by immunological techniques. In
      conclusion, our analysis showed some serious pitfalls of the morphology in T-ALL,
      clearly indicating the need for immunological analysis of the leukaemic cells.
      However, morphology remains an essential component of the diagnostic repertoire,
      especially when the marrow is difficult to aspirate and in cases with equivocal
      immunological findings. Furthermore, recognition of a separate myeloid leukaemic
      component in addition to the lymphatic one requires a morphological analysis.

PMID- 9163605
TI  - Further characterization of morphologically defined typical and atypical CLL: a
      clinical, immunophenotypic, cytogenetic and prognostic study on 390 cases.
AB  - We analysed a group of 390 patients, diagnosed with chronic lymphocytic leukaemia
      (CLL). Cases were subclassified as morphologically typical and atypical CLL
      according to the criteria of the FAB proposal. Typical CLL cases were mostly
      diagnosed at a low-risk stage (Binet A/Rai 0), required no immediate treatment
      and expected a long survival; atypical CLL cases mostly presented at a more
      advanced risk stage (Binet B/Rai I-II), usually required immediate treatment and
      their survival was shorter. Moreover, clinical staging was of prognostic
      significance in typical but not in atypical cases. In typical CLL, del(11q) was
      the most common chromosomal abnormality (21%) whereas in atypical CLL trisomy 12
      was found in about 65% of the cases documented with an abnormal karyotype.
      Although chromosomal abnormalities were associated with a poor survival in
      typical CLL, they are of no prognostic significance in atypical CLL. Based on
      these data, we conclude that subtyping CLL by morphology enables the
      identification of two groups of cases, each characterized by a specific clinical
      presentation, different cytogenetic abnormalities and prognostic parameters. We
      speculate that these two groups may represent two related, but different,
      diseases with different prognostic parameters and a different survival.

PMID- 9163606
TI  - Cyclophosphamide therapy for pure red cell aplasia associated with granular
      lymphocyte-proliferative disorders.
AB  - Granular lymphocytes have been characterized as cells with azurophilic granules
      in the cytoplasm. Patients with increased numbers of granular lymphocytes are
      designated as granular lymphocyte-proliferative disorders (GLPDs). A variety of
      haematological abnormalities are associated with T-cell-lineage GLPD. Among
      these, pure red cell aplasia is frequent, and adequate therapy is required. Seven
      patients with pure red cell aplasia, or a related condition complicating T-cell
      lineage GLPD, were entered into this study. Cyclophosphamide was initiated at a
      daily oral dose of 100 mg. After 2 weeks the dose was reduced to 50 mg/d, and
      maintained at that dose. Cyclophosphamide was administered until the lymphocyte
      count was <1 x 10(9)/l and T-cell receptor-beta gene analysis was used to monitor
      the response to treatment. All the patients were successfully treated,
      irrespective of their former treatment. Clinical remission was associated with
      the disappearance of the abnormal granular lymphocyte clone, as detected by
      Southern blot hybridization analysis. Therapeutic responses began after 8 weeks,
      and clinical complete remissions were obtained after 6 months. Oral
      cyclophosphamide monotherapy can successfully treat the pure red cell aplasia
      associated with T-cell-lineage GLPD.

PMID- 9163607
TI  - Absence of IL-6 receptor expression in fresh childhood Burkitt's lymphoma cells
      and induction of IL-6 receptors by Epstein-Barr virus in vitro.
AB  - Interleukin-6 (IL-6) is a cytokine which is necessary for the differentiation of
      activated B cells and growth of early haemopoietic progenitors. It is used for ex
      vivo expansion of myeloid progenitors in the setting of high-dose chemotherapy
      with autologous bone marrow transplantation (BMT). Expression of the IL-6
      receptor (IL-6R) was examined in six fresh Burkitt's lymphoma (BL) cell
      preparations and 12 BL cell lines by reverse transcriptase polymerase chain
      reaction (RT-PCR) and flow cytometry (FCM). Inducibility of IL-6R mRNA expression
      by Epstein-Barr virus (EBV) was studied by comparing two uninfected cell lines
      with the same cell lines infected by EBV The phenotype of the BL cells lines was
      analysed by FCM and by proliferation assays in the presence of anti-IgM
      antibodies. None of the fresh BL cells expressed the IL-6 receptor. The BL cell
      lines expressed varying degrees of IL-6R mRNA and protein. In vitro infection of
      EBV-negative BL cell lines resulted in up-regulation of IL-6R mRNA. There was no
      proliferative response of the BL cell lines to IL-6, including the cells that
      expressed the receptor. Compared to uninfected BL cell lines, EBV-infected cell
      lines and lymphoblastoid cell lines (LCLs) showed a weaker or no response to anti
      IgM antibodies, indicating a more mature phenotype of these cells. We conclude
      that the IL-6 receptor is not expressed in fresh childhood BLs, but only in BL
      cell lines. EBV infection in vitro leads to an up-regulation of IL-6R mRNA but
      not to increased proliferation. This makes growth stimulation of contaminating BL
      cells in the setting of autologous BMT unlikely.

PMID- 9163608
TI  - Role of the CD40 and CD95 (APO-1/Fas) antigens in the apoptosis of human B-cell
      malignancies.
AB  - Ligation of CD40 inhibits apoptosis and stimulates proliferation of normal B
      cells, whereas ligation of CD95 (APO-1/Fas) induces apoptosis of activated
      lymphocytes. Aberrant signalling through the CD40 and CD95 antigens could thus
      participate in the pathogenesis of lymphoid malignancies. The expression and
      function of CD40 and CD95 on neoplastic B cells from patients with acute
      lymphoblastic leukaemia (ALL), chronic lymphocytic leukaemia (CLL) and non
      Hodgkin's lymphoma (NHL) were examined. CD40 was expressed by all 30 B-cell
      tumours, whereas CD95 was detected on neoplastic B cells in only one of 10 cases
      of ALL, two of 10 cases of CLL, and three of 10 cases of NHL. Incubation with an
      agonistic CD95 monoclonal antibody (MoAb) did not augment apoptosis in any of the
      unstimulated B-cell neoplasms. CD40 triggering did not consistently inhibit
      spontaneous apoptosis, but ultimately stimulated the growth of neoplastic B cells
      in most cases. Furthermore, CD40 activation led to up-regulation of the CD95
      antigen in all 30 B-cell neoplasms. Ligation of CD95 on CD40-activated tumour
      cells augmented apoptosis in five of 10 ALL, three of 10 CLL, and nine of 10 NHL
      cases. The degree of apoptosis induced by CD95 triggering was greater for NHL
      cells than for ALL cells or CLL cells. Bcl-2 expression by ALL and NHL cells was
      substantially decreased after in vitro culture, whereas Bcl-2 expression by CLL
      cells was not significantly changed. However, there was no correlation between
      the level of Bcl-2 expression and sensitivity to CD95-mediated apoptosis. Thus,
      factors other than levels of CD95 and Bcl-2 determine susceptibility of malignant
      B cells to apoptosis after CD95 triggering. CD40-activated lymphoma cells appear
      to be very sensitive to CD95-mediated apoptosis, suggesting potential strategies
      for treatment of NHL. Elucidation of the mechanisms underlying resistance of ALL
      and CLL cells to CD95 triggering may facilitate the development of novel
      therapeutic approaches to these diseases as well.

PMID- 9163609
TI  - Expression of Apo-1/Fas (CD95), Bcl-2, Bax and Bcl-x in myeloma cell lines:
      relationship between responsiveness to anti-Fas mab and p53 functional status.
AB  - The down-regulation of apoptosis may be an essential mechanism for tumour cell
      expansion in slowly proliferating tumours such as multiple myeloma. We studied
      eight myeloma cell lines for the presence of Bcl-2, which inhibits apoptosis, of
      Bax, which counteracts Bcl-2, of Bcl-x(L) and Bcl-x(S), which act in an anti- and
      pro-apoptotic fashion, respectively, and of Apo-1/Fas, which induces programmed
      cell death, when activated by the Apo-1/Fas ligand or the relevant monoclonal
      antibody (mab). All cell lines constitutively expressed homogenous amounts of Bcl
      2, but displayed different amounts of Bax and Bcl-x proteins. The Apo-1/Fas
      antigen could be detected in seven out of eight myeloma lines, but expression
      levels varied considerably. The relative expression levels of Apo-1/Fas
      correlated with that of Bax, but not with that of Bcl-2 or Bcl-x subtypes.
      Furthermore, the effectiveness of the Apo-1/Fas mab was associated with the
      relative expression levels of the Apo-1/Fas and with that of the Bax antigen, but
      not with that of the Bcl-2 and Bcl-x antigens. We further showed that wild-type
      p53 function is not required for Apo-1/Fas-induced apoptosis, nor is it necessary
      for the expression of Bax or Apo-1/Fas antigens in myeloma. In conclusion, our
      results suggest a p53-independent co-regulation of Apo-1/Fas and Bax, as well as
      a role for Bax in Apo-1/Fas-induced apoptosis in myeloma.

PMID- 9163610
TI  - Multiple myeloma cells are protected against dexamethasone-induced apoptosis by
      insulin-like growth factors.
AB  - Multiple myeloma cell lines express functional receptors for insulin-like growth
      factors (IGFs) and several cell types that make up the bone marrow
      microenvironment produce these cytokines. This suggests that IGFs may play a role
      in survival and/or expansion of the malignant clone within the marrow in patients
      with multiple myeloma. We tested the effects of these growth factors on myeloma
      cells challenged with dexamethasone. Dye exclusion and MTT assays demonstrated
      that both IGF-I and IGF-II protected the 8226 and dox-40 myeloma cell lines and
      three primary myeloma cultures from dexamethasone-induced cytotoxicity in a dose
      dependent fashion. Morphologic studies of target cells and their nuclei as well
      as DNA electrophoresis confirmed the IGFs afforded protection against
      dexamethasone-induced apoptosis. Insulin also protected but was less impressive
      and required much higher concentrations. IGFs also protected against
      cycloheximide-induced apoptosis but were ineffective against serum starvation,
      topoisomerase II inhibitors, or anti-fas antibodies. IGF-induced protection
      against dexamethasone was not associated with any alteration in quantitative or
      qualitative expression of BCL-2, BAX or BCL-X proteins. These data indicate that
      insulin-like growth factors may play a role in maintenance of the malignant clone
      in patients with myeloma by protecting tumour cells from apoptotic death.

PMID- 9163611
TI  - Elevated levels of basic fibroblast growth factor in megakaryocytes and platelets
      from patients with idiopathic myelofibrosis.
AB  - Idiopathic myelofibrosis, or agnogenic myeloid metaplasia, is a chronic
      myeloproliferative disorder characterized by clonal expansion and marrow
      fibrosis. Although marrow fibrosis appears to be a reactive process, it
      substantially contributes to impaired haemopoiesis. During the last few years the
      implication of megakaryocyte-derived growth factors in its pathogenesis has been
      documented. We previously reported increased expression of TGF-beta in patients
      with idiopathic myelofibrosis. In the present study we show that circulating
      megakaryocytic cells from such patients expressed high levels of basic fibroblast
      growth factor (bFGF). An increased expression of bFGF was also detected in
      patients' platelets. Under culture conditions, bFGF present in megakaryocytic
      cells was not exported into the medium. consistent with the fact that bFGF is
      devoid of a secretion peptide signal. Interestingly, this lack of bFGF secretion
      was observed in all patients but one, who was in an accelerated phase of the
      disease and presented an important percentage of circulating megakaryoblasts.

PMID- 9163612
TI  - Thrombopoietin-responsive essential thrombocythaemia with myelofibrosis.
AB  - Platelet-derived growth factor (PDGF) and other cytokines released from
      megakaryocytes are thought to play a crucial role in the pathogenesis of
      myelofibrosis. We describe a patient with essential thrombocythaemia (ET) who
      developed myelofibrosis with an increased level of serum thrombopoietin (TPO).
      Recombinant human (rh) TPO stimulated the proliferation and spontaneous
      megakaryocyte colony formation of the neoplastic cells in the peripheral blood.
      Moreover, serum concentrations of PDGF, platelet factor 4, and beta
      thromboglobulin were elevated and the production of these growth factors from the
      megakaryocyte progenitors was augmented with the addition of rhTPO in vitro.
      These results indicate that TPO may contribute to the development of
      myelofibrosis in ET.

PMID- 9163613
TI  - Low-dose aspirin in polycythaemia vera: a pilot study. Gruppo Italiano Studio
      Policitemia (GISP).
AB  - In this pilot study, aimed at exploring the feasibility of a large-scale trial of
      low-dose aspirin in polycythaemia vera (PV), 112 PV patients (42 females, 70
      males. aged 17-80 years) were selected for not having a clear indication for, or
      contraindication to, aspirin treatment and randomized to receive oral aspirin (40
      mg/d) or placebo. Follow-up duration was 16 +/- 6 months. Measurements of
      thromboxane A2 production during whole blood clotting demonstrated complete
      inhibition of platelet cyclooxygenase activity in patients receiving aspirin.
      Aspirin administration was not associated with any bleeding complication. Within
      the limitations of the small sample size, this study indicates that a
      biochemically effective regimen of antiplatelet therapy is well tolerated in
      patients with polycythaemia vera and that a large-scale placebo-controlled trial
      is feasible.

PMID- 9163614
TI  - Comparison of fluorescent consensus IgH PCR and allele-specific oligonucleotide
      probing in the detection of minimal residual disease in childhood ALL.
AB  - The sensitivity of detection of residual disease by two IgH PCR strategies,
      fluorescent framework 3 (Ffr3) and allele-specific oligonucleotide probing
      (ASOP), was compared in 57 'remission' BM samples obtained from 19 children with
      B-lineage acute lymphoblastic leukaemia (ALL). Oligonucleotide probing was more
      sensitive than FFr3 PCR in 10/16 cases, achieving a sensitivity of 0.01% or
      greater in 15/16 cases. Comparable sensitivities were obtained in the six
      remaining cases; the FFr3 PCR achieving a sensitivity of 0.1% or greater in 14/16
      cases. 39/57 'remission' BM samples analysed showed no evidence of MRD by either
      technique although 18 were positive by ASOP and 14 positive by FFr3 PCR. The
      level of disease was estimated to be 0.01% or less in the four false negative
      samples.

PMID- 9163615
TI  - Outcome and lineage involvement in t(12;21) childhood acute lymphoblastic
      leukaemia.
AB  - The t(12;21)(p13;q22) translocation has been described recently as the most
      recurrent genetic lesion in paediatric acute lymphoblastic leukaemias (ALLs). It
      has also been associated with B-precursor lineage involvement and good outcome.
      We tested 51 diagnostic paediatric ALLs and found 11 cases with molecular
      evidence of the t(12;21). Interestingly, amongst t(12;21) positive patients, we
      report three cases with hybrid phenotype, and two cases showing an aggressive and
      fatal disease. Our data show that the t(12;21) does not represent an independent
      good-risk indicator. Long follow-ups and additional molecular investigations are
      needed to assess the prognostic and pathogenetic relevance of t(12;21) in
      childhood ALLs.

PMID- 9163616
TI  - Rarity of microsatellite genomic instability in B-cell non-Hodgkin's lymphomas in
      hepatitis C virus-infected patients.
AB  - Several groups have emphasized the likely implication of the hepatitis C virus
      (HCV) in a fraction of B-cell non-Hodgkin's lymphomas. Since only a minority of
      patients with HCV infection and monoclonal mixed cryoglobulinaemia develop overt
      lymphoma, the identification of predisposing factors has relevant clinical
      implications. The replication error phenotype (RER+), as revealed by widespread
      microsatellite instability, is caused by defects in DNA mismatch repair genes,
      and has been frequently disclosed in subsets of B-cell lymphomas with underlying
      infection and chronic inflammation. We therefore investigated the occurrence of
      the RER+ phenotype in a series of eight consecutive B-cell NHLs in patients with
      chronic infection by HCV. A polymerase chain reaction-based assay was used to
      analyse an extended panel of 15 microsatellite loci. Microsatellite instability
      was not observed in six tumour samples in any locus; the two remaining cases
      showed instability at only one locus. Therefore genetic instability by defects in
      DNA mismatch repair genes should not represent the general mechanism predisposing
      to overt lymphoma in HCV-infected patients. Although a clearer definition of HCV
      related B-cell disorders should better address future studies on genetic
      instability in larger series, we recommend additional oncogenetic pathways as the
      target of further research.

PMID- 9163618
TI  - Biological properties of peripheral blood progenitor cells mobilized by
      cyclophosphamide and granulocyte colony-stimulating factor.
AB  - Patients transplanted with mobilized blood progenitor cells (PBPC) recover their
      neutrophil counts more rapidly than patients transplanted with bone marrow even
      when they receive the same dose/kg of granulocyte-macrophage colony-forming cells
      (CFU-GM). Here we have sought a biological explanation for this phenomenon. Most
      CD34-positive PBPC are quiescent (<1% in S phase) when they are collected from
      the bloodstream of patients treated with cyclophosphamide and granulocyte colony
      stimulating factor (G-CSF), but we have shown that they are able to resume
      proliferation rapidly in vitro by measuring the kinetics of CFU-GM production by
      primitive plastic-adherent (Pdelta) cells. Also, Pdelta cells in PBPC harvests,
      unlike normal marrow Pdelta cells, were insensitive to cell-cycle restraint
      imposed by contact with marrow-derived stromal cells. We found that Pdelta cells
      in PBPC collections produce relatively more CFU-GM and relatively fewer BFU-E
      than Pdelta cells in bone marrow, indicating that granulopoiesis might occur at
      the expense of erythropoiesis, but we were unable to find any differences in the
      kinetics of granulocytic maturation between PBPC and bone marrow. Our
      interpretation of these findings is that transplanted PBPC rapidly enter the cell
      cycle and contact with stromal cells in the marrow does not reduce the proportion
      of progenitors participating in neutrophil production. Consequently. neutrophil
      recovery after PBPC infusion is more rapid than neutrophil recovery after marrow
      infusion. Granulopoiesis at the expense of erythropoiesis may also contribute to
      this effect.

PMID- 9163617
TI  - Allogeneic blood or marrow transplantation for chronic lymphocytic leukaemia:
      timing of transplantation and potential effect of fludarabine on acute graft
      versus-host disease.
AB  - The outcome of allogeneic haemopoietic transplants including the rate of immune
      complications for patients with chronic lymphocytic leukaemia (CLL) refractory to
      or relapsing after chemotherapy with fludarabine was analysed. Fifteen patients
      with advanced CLL who received allogeneic transplantation were prospectively
      analysed. All patients had previously received chemotherapy with fludarabine for
      3-15 courses; 12 were refractory. The median number of circulating CD4+ and CD8+
      lymphocytes at the time of transplant was 0.49 x 10(9)/l and 0.23 x 10(9)/l,
      respectively. One patient was transplanted from a one HLA-antigen mismatched
      unrelated donor. Three others received a one or two antigen mismatched graft and
      11 had HLA-identical sibling donors. Patients received cyclosporine or tacrolimus
      in addition to methotrexate or methylprednisolone for prophylaxis of acute graft
      versus-host disease (aGVHD). Fourteen patients engrafted; one patient had graft
      failure, but recovered after therapy with intravenous immunoglobulin. 13 (87%)
      achieved complete remission (CR). Nine (53%) remain alive and in CR with a median
      follow-up of 36 (range 3-60) months. None developed visceral graft-versus-host
      disease. These data compared favourably to published reports in other leukaemia
      patients and for patients with CLL who received a comparable immunosuppressive
      therapy but without prior fludarabine exposure. This data indicates that
      allogeneic haemopoietic transplantation can induce durable remission in patients
      with CLL refractory to fludarabine and that it is reasonable to delay
      transplantation until failure of fludarabine therapy. It also suggests that prior
      exposure to fludarabine may decrease the incidence of severe aGVHD, possibly
      through its immunosuppressive effects. Further studies are warranted to evaluate
      this observation.

PMID- 9163619
TI  - Colony counting is a major source of variation in CFU-GM results between centres.
AB  - The results for colony forming unit granulocyte-macrophage (CFU-GM) assays vary
      substantially between centres. It is possible that colony counting is largely
      responsible for this discrepancy. In order to examine this exclusively from the
      many factors that make up the CFU-GM assay, we performed a colony counting
      exercise involving 11 laboratories. Two-way analysis of variance showed a highly
      significant difference (P = 0.0001) in the counts obtained from the centres. One
      centre was found to score consistently high and two others scored consistently
      low numbers of colonies. This suggests that identification of colonies is a major
      source of variation between centres.

PMID- 9163620
TI  - Collection of peripheral blood stem cells from normal donors 60 years of age or
      older.
AB  - We report 14 normal peripheral blood stem cell (PBSC) donors > or = 60 years of
      age who had cytokine mobilization followed by PBSC apheresis for allogeneic
      transplantation. Mobilization was achieved with filgrastim (6 microg/kg twice
      daily). Their median age was 63.5 years (range 60-77), and 43% had a positive
      medical history, mainly hypertension and/or cardiac problems. Their median pre
      apheresis leucocyte count (x 10(9)/l) was 38.6 (range 29.6-63.4). The median
      apheresis yield (x 10(6) CD34+ cells/litre blood processed, first apheresis) was
      27.9 (range 1.6-54.8). The target cell dose (> or = 4 x 10(6) CD34+ cells/kg
      recipient) was reached with one procedure in eight (57%) donors. Filgrastim
      related adverse events were acceptable and apheresis was well tolerated. When
      compared to younger donors (< 60 years of age), a trend to a lower CD34+
      apheresis yield and a requirement for more than one apheresis to achieve the
      collection target (> or = 4 x 10(6) CD34+ cells/kg) was evident. Although older
      (> or = 60 years) donors seem to mobilize less effectively, these data suggest
      that PBSC collection from them is feasible and has an acceptable short-term
      safety profile.

PMID- 9163621
TI  - Concordant expression of class II and class III CD34 epitopes on haemopoietic
      cells in leukapheresis and cord blood samples with CD45/CD34 dual staining.
AB  - We used flow cytometry with CD45/CD34 dual antibody labelling to investigate the
      relative expression of class II and class III CD34 epitopes on haemopoietic
      progenitor cells (HPC) in 22 leukapheresis and cord blood samples. There was a
      close correlation between class II (QBEnd-10) and class III (clone 581) CD34+
      cells (R2= 0.975, ratio of class III to class II CD34+ count 1.24 +/- 0.04). The
      linear relationship between class II and III CD34 epitopes on HPC suggests that
      the choice of antibody class is not a source of random variation in the quality
      assurance of CD34+ cell enumeration.

PMID- 9163622
TI  - Prevalence of GBV-C/HGV, a novel 'hepatitis' virus, in patients with aplastic
      anaemia.
AB  - GBV-C or hepatitis G virus (GBV-C/HGV) is a novel RNA virus with similarities to
      members of the Flaviviridae family, especially hepatitis C. Viral RNA is detected
      in about 1.5% of American blood donors, with higher prevalence in multiply
      transfused patients and in individuals with hepatitis or liver disease. Some
      cases of aplastic anaemia follow apparent non-A, non-B, non-C viral hepatitis,
      and GBV-C viraemia has been described in three case reports of hepatitis
      associated aplastic anaemia. We tested clinical samples from patients with
      aplastic anaemia with or without recent hepatitis for the presence of GBV-C/HGV.
      Virus was detected in a total of 15/57 (26.3%) of patients with aplastic anaemia
      and 12/52 (23.1%) of multiply transfused control patients. Sequencing of the 188
      base pair NS3 helicase PCR product in the serum of five individuals indicated the
      same high degree of sequence variation as has been seen among other isolates of
      the virus. GBV-C/HGV does not appear to be implicated in the aetiology of
      aplastic anaemia.

PMID- 9163623
TI  - Fibrinogen degradation products in patients with the Quebec platelet disorder.
AB  - The Quebec platelet disorder is a serious bleeding disorder associated with
      proteolysis of alpha-granular proteins, including fibrinogen. We evaluated
      fibrinogen degradation product (FDP) assays as screening tests for this disorder.
      Patients with the Quebec platelet disorder (13/13) had elevated serum FDPs (P <
      0.01) due to secreted degraded platelet fibrinogen, but normal plasma FDPs and D
      dimers. Unrelated controls with bleeding disorders (32/34) had undetectable FDPs,
      and controls with FDPs due to disseminated intravascular coagulation (DIC) and
      other illnesses (11/11) had elevated FDPs in all assays (P < 0.01). Immunoblot
      analyses indicated plasma fibrinogen was normal in the Quebec patients and
      platelet FDPs were found in their platelet lysates, releasates and serum samples.
      Their platelet FDPs were not altered by treatment with fibrinolytic inhibitors
      and were different from the FDPs in DIC and in plasmin-digested fibrinogen. Tests
      for serum FDPs may provide a simple rapid way to screen for the Quebec platelet
      disorder.

PMID- 9163624
TI  - Beta-thalassaemia due to a seventeen basepair deletion.

PMID- 9163625
TI  - Frequency of factor V Leiden (Arg506Gln) in Turkey.

PMID- 9163626
TI  - Post-splenectomy thrombosis and haemolytic anaemias.

PMID- 9163627
TI  - Vaccination against influenza in multiple myeloma.

PMID- 9163628
TI  - Beta-thalassaemia heterozygotes with alpha-globin gene triplication.

PMID- 9163629
TI  - Human herpesvirus 8 in Kaposi's sarcoma of an HIV-negative Japanese woman with
      adult T-cell leukemia.

PMID- 9163630
TI  - Successful treatment of juvenile rheumatoid arthritis associated haemophagocytic
      syndrome by cyclosporin A with transient exacerbation by conventional-dose G-CSF.

PMID- 9163631
TI  - Compliance with nasal CPAP therapy for obstructive sleep apnoea: how much is
      enough?

PMID- 9163632
TI  - Anti-inflammatory effects of macrolide antibiotics.

PMID- 9163633
TI  - Residual effect of nCPAP applied for part of the night in patients with
      obstructive sleep apnoea.
AB  - The aim of the present study was to assess whether nasal continuous positive
      airway pressure (nCPAP) treatment, applied for only a few hours at the beginning
      of the night, has any residual effect on sleep and breathing during the ensuing
      hours of unassisted sleep in patients with obstructive sleep apnoea syndrome
      (OSAS). In 27 patients with newly-diagnosed OSAS, effective nCPAP was applied
      during the first part of the night and then withdrawn. Polysomnographic
      parameters after nCPAP withdrawal were compared with those of the corresponding
      part of the diagnostic polysomnography performed a few days or weeks before and
      with those of the first part of night on nCPAP. After 255+/-63 (mean+/-SD) min of
      sleep with normalization of sleep and breathing parameters under nCPAP, there was
      partial improvement of OSAS severity during the remaining 124+/-56 min of
      nocturnal sleep without treatment; mean oxygen saturation, desaturation index
      (equivalent to the apnoea/hypopnoea index) and movement arousal index all
      improved significantly with respect to the diagnostic night (p=0.001). This
      improvement was not accounted for by a change in sleep architecture. We conclude
      that there is an improvement in severity of obstructive sleep apnoea syndrome
      after only 4 h of nasal continuous positive airway pressure. This carryover
      effect could explain why a number of patients with obstructive sleep apnoea
      syndrome apply nasal continuous positive airway pressure for only part of the
      night or not every night.

PMID- 9163634
TI  - Respiratory muscle function and control of breathing in patients with acromegaly.
AB  - Increase in lung size has been described in acromegalic patients, but data on
      respiratory muscle function and control of breathing are relatively scarce. Lung
      volumes, arterial blood gas tensions, and respiratory muscle strength and
      activation during chemical stimulation were investigated in a group of 10
      patients with acromegaly, and compared with age- and sex-matched normal controls.
      Inspiratory muscle force was evaluated by measuring pleural (Ppl,sn) and
      transdiaphragmatic (Pdi,sn) pressures during maximal sniffs. Dynamic pleural
      pressure swing (Ppl,sw) was expressed both as absolute value and as percentage of
      Ppl,sn. Expiratory muscle force was assessed in terms of maximal expiratory
      pressure (MEP). In 8 of the 10 patients, ventilatory and respiratory muscle
      responses to hyperoxic progressive hypercapnia and to isocapnic progressive
      hypoxia were also evaluated. Large lungs, defined as total lung capacity (TLC)
      greater than predicted (above 95% confidence limits), were found in five
      patients. Inspiratory or expiratory muscle force was below normal limits in all
      but three patients. During unstimulated tidal breathing, respiratory frequency
      (fR) and mean inspiratory flow (tidal volume/inspiratory time (VT/tI)) were
      greater, while inspiratory time (tI) was shorter than in controls. Minute
      ventilation (V'E) and mean inspiratory flow response slopes to hypercapnia were
      normal In contrast, four patients had reduced delta(VT/tI)/arterial oxygen
      saturation (Sa,O2) and three had reduced deltaV'E/Sa,O2. Ppl,sw(%Ppl,sn) response
      slopes to increasing end-tidal carbon dioxide tension (PET,CO2) and decreasing
      Sa,O2 did not differ from the responses of the normal subjects, suggesting normal
      central chemoresponsiveness. At a PET,CO2 of 8 kPa or an Sa,O2 of 80%, patients
      had greater fR and lower tI compared with controls. Pdi,sn and Ppl,sn related
      both to deltaV'E/deltaSa,O2 (r=0.729 and r=0.776, respectively) and
      delta(VT/tI)/deltaSa,O2 (r=0.860 and r=0.90, respectively). Pdi,sn also related
      both to deltaV'E/deltaPET,CO2 (r=0.8) and delta(VT/tI)/deltaPET,CO2 (r=0.76). In
      conclusion, the data suggest the relative independence of pneumomegaly and
      respiratory muscle strength. Peripheral (muscular) factors appear to modulate a
      normal central motor output to give a more rapid pattern of breathing.

PMID- 9163635
TI  - A noninvasive electromyographic study on threshold and intensity of cough in
      humans.
AB  - The assessment of cough threshold and intensity is important in respiratory
      medicine. We have developed a method for objectively and noninvasively assessing
      cough threshold and intensity of expiratory muscle efforts in response to
      inhalation of ultrasonically nebulized distilled water (UNDW). Thirty (83%) out
      of 36 volunteers studied coughed in response to UNDW inhalation. Cough threshold
      was taken as the lowest nebulizer output (mL x min(-1)) that induced cough in two
      challenges performed at a 30 min interval. At threshold level, repeatability of
      peak and slope of the integrated electromyographic (IEMG) activity of abdominal
      muscles was evaluated. Short- and long-term repeatability of cough threshold were
      evaluated in 15 subjects following a 3 h and a 6-9 month interval, respectively.
      Dose-response relationships between nebulizer outputs and IEMG-related variables
      were also investigated, as were the correlations between the latter and
      expiratory flow during voluntary coughing. The median (1st and 3rd quartile)
      cough threshold value was 0.89 (0.40 and 1.54) mL x min(-1). At threshold level,
      peak and slope of IEMG activity were highly reproducible. Cough threshold
      displayed a high degree of short- and long-term repeatability. Peak and slope of
      IEMG activity displayed a clear trend to increase (p<0.01) following inhalation
      of progressively higher UNDW outputs. Maximum flow during voluntary coughs of
      varying intensity correlated with the peak (p<0.05) and, more closely, with the
      slope (p<0.01) of abdominal IEMG activity. The assessment of cough threshold as
      well as the evaluation of the intensity of cough efforts by abdominal integrated
      electromyographic recordings may represent useful and reliable tools for cough
      research in humans.

PMID- 9163636
TI  - Histochemical properties of upper airway muscles: comparison of dilator and
      nondilator muscles.
AB  - The upper airway dilator muscles (UADMs) represent a subgroup of muscles in the
      pharyngeal area which, in addition to their roles in mastication, vocalization,
      etc., also have an important respiratory function. Failure of these muscles to
      maintain upper airway patency during sleep is important in the development of the
      obstructive sleep apnoea syndrome. In the present study, we evaluated the
      histochemical properties of the UADMs and compared them to those of neighbouring
      muscles without respiratory functions, and to the diaphragm, to determine whether
      the UADMs are specifically adapted to their respiratory role. Our results, both
      in dogs and rats, indicate that the dilator and nondilator upper airway muscles
      are similar and differ from the diaphragm. In rats, there were significantly less
      type I fibres (<12% as compared to 42% for the diaphragm) and more type IIb
      fibres (39-67% as compared to 27% for the diaphragm). A similar pattern was seen
      in dogs: type I fibres <38% as compared to 46% for the diaphragm, and type IIb
      fibres, 29-35% as compared to 10% for the diaphragm. These findings suggest that
      the upper airway dilator muscles are not specifically designed for their
      respiratory role. They may fail in the presence of increased loads, often
      encountered in patients with obstructive sleep apnoea, unless appropriate
      adaptive structural changes take place.

PMID- 9163637
TI  - Effect of roxithromycin on airway responsiveness in children with bronchiectasis:
      a double-blind, placebo-controlled study.
AB  - Increased airway responsiveness (AR) is frequently associated with
      bronchiectasis. Roxithromycin is a new semisynthetic macrolide antibiotic that
      also has anti-inflammatory activities. This study was designed to see whether
      roxithromycin could favourably alter the degree of AR in patients with
      bronchiectasis and increased AR. Twenty five children with bronchiectasis, who
      had an increased AR (defined as a provocative concentration of methacholine
      causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20) <25 mg
      x mL(-1) evaluated by the dosimeter method), were randomized, double-blind into
      two parallel groups. Thirteen of the children were treated with roxithromycin (4
      mg x kg(-1) b.i.d.) for 12 weeks and 12 received placebo. FEV1, sputum purulence
      and leucocyte scores were assessed every 3 weeks. To estimate AR, high-dose
      methacholine challenge tests were performed before and after treatment. On the
      dose-response curve to methacholine, PD20 and maximal response (two indices of
      AR) were measured. Changes in FEV1 were not observed during the course of the
      study in both groups. A significant improvement in sputum features was noted
      after 6 weeks of treatment in the roxithromycin group. After 12 weeks of
      roxithromycin therapy, the geometric mean (range of 1 SD) of provocative
      cumulative dose producing a 20% fall in FEV1 (PD20) increased significantly
      (p<0.01) to 169.2 (83.2-344.2) breath units (BU) (1 BU denotes one inhalation of
      1 mg x mL(-1) methacholine) and the mean+/-SD of maximal response decreased
      significantly (p<0.01) to 32.5+/-6.8%, as compared with the initial values (PD20
      87.1 (47.3-160.4) BU; maximal response 40.9+/-7.4%). No significant changes in
      either parameter were observed in the placebo group. Our results indicate that
      roxithromycin may decrease the degree of airway responsiveness in patients with
      bronchiectasis and increased airway responsiveness. Further study is necessary to
      determine the mechanism by which roxithromycin reduces airway responsiveness in
      bronchiectasis and its clinical impact.

PMID- 9163638
TI  - Inhibition of PAF-induced expression of CD11b and shedding of L-selectin on human
      neutrophils and eosinophils by the type IV selective PDE inhibitor, rolipram.
AB  - We quantitatively determined whether the selective phosphodiesterase (PDE)
      inhibitor, rolipram, inhibits changes in the adhesion molecules CD11b and L
      selectin on platelet-activating factor (PAF)-stimulated human neutrophils and
      eosinophils in vitro. Incubations were performed in human whole blood obtained
      from healthy volunteers, to restrict activation by purification procedures and to
      simulate in vivo conditions, in which different cell types may interact, more
      closely. Receptor expression was measured after fixation of cells, using
      monoclonal antibodies and flow cytometry. Concentration-dependent inhibition of
      the PAF-induced CD11b expression and L-selectin shedding for neutrophils and
      eosinophils was observed with rolipram, dibutyryl cyclic adenosine monophosphate
      (cAMP), prostaglandin E2 (PGE2), and isoproterenol. However, these inhibitions
      did not exceed 50%. Preincubation with rolipram (10(-8) M) and subsequent
      incubation with isoproterenol (0.5x10(-8) M) or PGE2 (10(-8) M) induced a
      cumulative, but not synergistic, effect. Using the combination of rolipram with
      isoproterenol or PGE2, inhibition of PAF-induced L-selectin shedding from
      eosinophils was as high as 71+/-28 and 67+/-21%, respectively. Other inhibitions
      were below 50%. In conclusion, rolipram inhibits CD11b expression and L-selectin
      shedding of platelet-activating factor-stimulated neutrophils and eosinophils in
      whole blood in a concentration-dependent fashion. Inhibitions did not exceed 50%,
      even at high concentrations. The inhibition of platelet-activating factor induced
      shedding of L-selectin from eosinophils with a combination of rolipram and
      prostaglandin E2 or isoproterenol, however, was found to be approximately 70%.
      Inhibition of rolling adhesion of eosinophils may, therefore, be a mode of action
      of type IV phosphodiesterase inhibitors.

PMID- 9163639
TI  - The effect of a novel orally active selective PDE4 isoenzyme inhibitor (CDP840)
      on allergen-induced responses in asthmatic subjects.
AB  - Recent studies have suggested that theophylline, a nonspecific phospho-diesterase
      inhibitor, has useful anti-inflammatory actions in asthma. Phosphodiesterase 4
      (PDE4) represents the predominant PDE isoenzyme present in inflammatory cells.
      PDE4 inhibitors might, therefore, have beneficial effects in asthma. Side
      effects, specifically nausea, have limited the use of existing agents. CDP840 is
      an orally active, potent and selective PDE4 inhibitor. We have examined the
      effect of CDP840 on the allergen-induced asthmatic response, its possible modes
      of action, and its tolerability at therapeutic doses. A total of 54 patients were
      recruited to three double-blind, placebo-controlled studies. The first study
      examined the effect of CDP840 (15 mg b.i.d. for 9.5 days) on the allergen-induced
      asthmatic response in patients with known dual response to allergen. A second
      study examined the effect of CDP840 (15 mg b.i.d. for 9.5 days) on airway
      responsiveness to histamine. A third study examined whether single dose CDP840
      (15 and 30 mg) had significant bronchodilatory effects. In all studies, CDP840
      was well-tolerated, with no patients reporting nausea. CDP840 did not lead to
      changes in baseline forced expiratory volume in one second (FEV1) as compared to
      placebo. The late asthmatic response (LAR) to allergen, expressed as area under
      the curve at 3-8 h (AUC3-8h), was inhibited by 30% (p=0.016), an effect which
      persisted to the end of the observation period. The early asthmatic response
      (EAR) was unaffected, and there was no bronchodilatory effect at the doses used.
      Treatment with CDP840 did not affect bronchial hyperresponsiveness to histamine.
      In conclusion, CDP840 significantly attenuated the late asthmatic response to
      allergen challenge in the absence of any bronchodilatory or histamine antagonist
      effect. This suggests that CDP840 may exert its effects via an anti-inflammatory
      mechanism.

PMID- 9163640
TI  - Pre- and postjunctional inhibitory effects of fenspiride on guinea-pig bronchi.
AB  - Fenspiride is a drug with potential benefits in the treatment of obstructive
      airways disease. It has antibronchoconstriction and anti-inflammatory properties.
      The aim of this study was to investigate the effect of this drug on the
      contractions induced in the guinea-pig isolated main bronchus and perfused lung
      by electrical field stimulation (EFS) or exogenously added agents. Bronchi were
      stimulated transmurally in the presence of indomethacin 10(-6) M and propranolol
      10(-6) M, and isometric tension was measured. In the perfused lung model
      calcitonin gene-related peptide (CGRP) release was determined in the perfusate
      fractions as a measure of neuropeptide production. Two successive contractile
      responses were observed: a rapid cholinergic contraction, followed by a long
      lasting contraction due to local release of neuropeptides from C-fibre endings.
      Fenspiride (10(-6) to 10(-4) M) inhibited the nonadrenergic, noncholinergic
      (NANC) component of the contraction of the guinea-pig isolated main bronchus
      induced by EFS. Fenspiride significantly affected contractions induced by
      exogenously added substance P or [Nle10]-NKA(4-10) only at concentrations higher
      than 10(-3) M. In the guinea-pig perfused lung, fenspiride inhibited low pH- but
      not capsaicin-evoked release of CGRP. At higher concentrations (10(-4) M to 3x10(
      4) M) fenspiride exhibited a significant inhibitory effect both on the
      cholinergic component of contractile response induced by EFS in the guinea-pig
      isolated main bronchus and on exogenously added acetylcholine. In conclusion, the
      result of this study suggests that fenspiride, in moderate concentrations,
      reduces the release of neuropeptides, including tachykinins, from sensory nerve
      endings at a prejunctional level. At higher concentrations, postjunctional
      actions on bronchial smooth muscle are also present.

PMID- 9163641
TI  - Is nitric oxide in exhaled air produced at airway or alveolar level?
AB  - The aim of this study was to determine whether the nitric oxide (NO) measured in
      exhaled air is produced at airway or alveolar level. Exhaled NO was measured
      using a chemiluminescence analyser, and carbon dioxide (CO2 concentration using a
      Morgan capnograph in single exhalations in 12 healthy subjects (mean age 32 yrs;
      6 males and 6 females). For each subject, five exhalations were made directly
      into the NO analyser and five were made through a T-piece system, which allowed
      measurement of expiratory flow rate. The peak NO levels measured via the T-piece
      system were 41.2 (SEM 10.8) parts per billion (ppb), significantly lower than
      direct levels 84.8 (14.0) ppb (p<0.001). The levels of NO tended to rise to an
      early peak and plateau, while the CO2 levels continued to rise to peak late in
      the exhalation. The mean times to reach peak NO levels were 32.2 s (direct) and
      23.1 s (T-piece), which were significantly different from that of peak CO2 levels
      50.5 s (direct) and 51.4 s (T-piece) (p<0.001). At peak NO level, the
      simultaneous CO2 level mean 4.9% (SEM 0.14)%, was significantly lower than the
      peak CO2 reached, 5.8 (0.21)% (p<0.001). We conclude that peak nitric oxide
      levels are dependent on measurement conditions. There are significant differences
      between the time to peak of carbon dioxide and nitric oxide. Therefore, most
      nitric oxide, unlike carbon dioxide, is produced in airways and not at alveolar
      level.

PMID- 9163642
TI  - Airway endothelin levels in asthma: influence of endobronchial allergen challenge
      and maintenance corticosteroid therapy.
AB  - Endothelins (ETs) are 21 amino acid peptides which, in addition to their other
      properties, are potent bronchoconstrictors. Whilst there is evidence of the
      involvement of ET in the pathophysiology of chronic asthma, its contribution to
      the acute allergic response is undefined. To examine this, we have undertaken
      segmental bronchoprovocation with allergen and saline at separate sites in six
      atopic asthmatics receiving treatment with bronchodilators only and six atopic
      asthmatics additionally receiving treatment with inhaled corticosteroids. Each
      challenged segment was lavaged 10 min after bronchoprovocation and concentrations
      of immunoreactive ET were measured in bronchoalveolar lavage fluid. In the non
      steroid-treated subjects, there were significantly lower ET levels at the
      allergen-challenged sites compared to the saline-challenged sites (p<0.05). In
      the steroid-treated subjects, on the other hand, there was no significant
      difference between the two sites. Levels of ET at the saline-challenged sites
      were significantly lower in the steroid-treated subjects compared to the non
      steroid-treated subjects (p<0.04). These findings do not support the hypothesis
      that allergen exposure in asthma results in immediate release of endothelin.
      However, release at later time-points and a role for endothelin in late-phase
      bronchoconstriction are not excluded.

PMID- 9163643
TI  - Bronchial and skin reactivity in asthmatic patients with and without atopic
      dermatitis.
AB  - It is unclear whether the presence and severity of atopic dermatitis (AD) is
      predictive for the occurrence and severity of early and late asthmatic responses
      to inhaled allergens. The aim of this study was to compare the bronchial effects
      of allergen inhalation challenge in allergic asthma (AA) and atopic dermatitis.
      We therefore studied these responses in: nine patients with mild-to-moderate AA
      without AD; eight patients with mild-to-moderate AA and mild AD; eight patients
      with severe AD and mild AA; and eight patients with severe AD without AA.
      Allergen challenge was performed by inhaling doubling doses until the dose
      provoking a 20% fall in forced expiratory volume in one second (PC20) was
      reached. The late asthmatic reaction (LAR) was defined as a fall of >20% in peak
      expiratory flow (PEF) between 3 and 8 h after the challenge. All but four of the
      patients with severe AD without AA developed an early asthmatic response (EAR). A
      LAR was seen in all patients with severe AD and mild AA, in four patients with
      mild AD and mild-to-moderate AA, and in three patients with mild-to-moderate AA
      without AD. The LAR was most pronounced in patients with a combination of mild AA
      and severe AD. This could be explained, in part, by a decreased skin sensitivity
      in these patients, which made the Cockcroft formula for prediction of PC20
      allergen less accurate in such patients. We conclude that patients with severe
      atopic dermatitis and mild asthma are at risk for developing pronounced late
      asthmatic responses after allergen exposure. This suggests that eosinophils
      activated in atopic dermatitis also predispose to airway inflammation.

PMID- 9163644
TI  - Atopy, lung function and bronchial responsiveness in symptom-free paediatric
      asthma patients.
AB  - In adolescence, some paediatric asthma patients will become symptom-free and
      require no further treatment. There is little information on the atopic status,
      lung function and bronchial responsiveness of these patients. Symptom-free asthma
      patients (n=118) aged 7.7-19.2 yrs, were evaluated 1 year after termination of
      therapy. Bronchial asthma had previously been diagnosed on the basis of recurrent
      wheezing episodes. Atopic status was assessed by skin-prick testing. Baseline
      lung function was measured by spirometry, flow-volume curve and plethysmography.
      Bronchial responsiveness was assessed nonpharmacologically by cold dry air
      challenge. Eighty one patients had at least one positive skin test result, and
      the remaining 37 were defined as nonatopic. In atopic subjects, the prevalence of
      bronchial hyperresponsiveness was significantly higher than in nonatopic patients
      (41 out of 81 versus 7 out of 37; p=0.001). Atopic subjects showed a
      significantly lower maximal expiratory flow at 25% remaining vital capacity
      (p<0.05) and a higher residual volume (p<0.05) than nonatopic subjects. Nonatopic
      subjects were significantly younger than atopic patients (p<0.01). These symptom-
      and medication-free paediatric and adolescent asthma patients could, thus, be
      divided into two groups: 1) atopic subjects with a tendency towards bronchial
      hyperresponsiveness; and 2) nonatopic subjects with better lung function and
      normal bronchial responsiveness In view of the increased understanding of the
      epidemiology of early childhood wheezing, these findings support the concept of
      different pathogenic mechanisms underlying wheezing episodes in early childhood.

PMID- 9163645
TI  - Changing prevalence of asthma in school children: evidence for diagnostic changes
      in asthma in two surveys 13 yrs apart.
AB  - It is still unclear whether the reported increase in the prevalence of asthma is
      real or due to changes in diagnostic criteria. The objectives of this study were
      to compare the prevalence of diagnosed asthma with the prevalence of respiratory
      symptoms, and to compare the association between asthma and other atopic diseases
      in 1981 and 1994. The study populations comprised randomly selected school
      classes in Oslo in 1981 (n=1,772) and 1994 (n=2,577). The main outcomes in these
      comparable cross-sectional studies of children, 6-16 yrs of age, were parent
      reported prevalence of diagnosed asthma, respiratory symptoms, eczema and hay
      fever. The questionnaire was identical in 1981 and 1994. The response rates were
      94% (1,674 out of 1,772) in 1981 and 85% (2,188 out of 2,577) in 1994. The
      lifetime prevalence of asthma increased from 3.4% in 1981 to 9.3% in 1994; odds
      ratio (OR) 2.9 (95% confidence interval (95% CI) 2.1-4.0) comparing 1994 to 1981.
      The prevalence of occasional wheezing increased from 9.0 to 10.8%; OR 1.2 (95% CI
      1.0-1.5), and attacks of wheezing from 3.7 to 6.8%; OR 1.8 (95% CI 1.3-2.5).
      Survival analyses for 3 year birth cohorts showed that asthma was more readily
      diagnosed in the latest birth cohort (1985-1988). The association between asthma
      and other atopic diseases decreased during the period under study. The increase
      in diagnosed asthma and respiratory symptoms supports a true increase in asthma.
      However, the larger increase in diagnosed asthma than wheezing and a reduced
      association between asthma and other atopic diseases suggest that the increase in
      asthma may be explained, in part, by changes in diagnostic criteria.

PMID- 9163646
TI  - Perception of airway narrowing in a general population sample.
AB  - In epidemiological studies, defining asthma as the presence of airway
      hyperresponsiveness (AHR) plus recent symptoms leaves two groups of subjects
      whose clinical significance is unclear: those with asymptomatic AHR, and those
      with symptoms only. The aim of the study was to determine whether subjects with
      symptoms only differ from the normal and asthmatic groups in the perception of
      airway obstruction. Six hundred and ninety seven adults completed a questionnaire
      of symptoms and underwent bronchial challenge with histamine to induce airway
      obstruction. Recent symptoms included wheeze and morning chest tightness in the
      last 12 months. AHR was defined as a provoking dose of histamine causing > or =
      20% fall in forced expiratory volume in one second (PD20FEV1) <3.9 micromol. At
      the end of the challenge test, subjects who felt wheezy or tight in the chest
      marked a value from 0 to 10 on a modified Borg scale, to describe the severity of
      the sensation. Subjects with asymptomatic AHR did not differ significantly from
      subjects with AHR plus recent symptoms (current asthma) either in the mean fall
      in FEV1 or in the median Borg score. In subjects with symptoms only, the mean
      Borg score was not significantly different from that of the asthmatic subjects,
      although mean fall in FEV1 differed significantly (p<0.0001). In subjects with
      symptoms only, chest tightness correlated significantly with the fall in forced
      vital capacity (FVC) (p= 0.011), but not with the fall in FEV1. Subjects with
      asymptomatic airways hyperresponsiveness were not poor perceivers of airway
      narrowing, but may underreport their symptoms. Subjects with symptoms only may
      have enhanced perception of small changes in lung function, particularly in
      forced vital capacity.

PMID- 9163647
TI  - Breathing pattern during bronchial challenge in humans.
AB  - Increases in minute ventilation (V'E) have been observed during exacerbations of
      asthma and in response to administration of histamine. However, it is not yet
      clear how the breathing pattern is affected, and whether the increase in V'E is
      found in general. In the present study, the effects of inhalation of histamine on
      respiratory frequency (fR), tidal volume (VT), V'E, and on functional residual
      capacity (FRC) were evaluated in 63 humans. Forty four subjects were
      hyperresponsive (BHR+). In each of these subjects, the doses of histamine applied
      for the present study (mean 3.5 mg x mL(-1)) caused a decrease in forced
      expiratory volume in one second (FEV1) that was greater than 20% of the control
      value. The dose of histamine applied in the 19 nonhyperresponsive subjects (BHR-)
      was substantially larger (8.0 mg x mL(-1)) whilst for this dose the decrease in
      FEV1 was less than 20% of control value. After histamine, fR was significantly
      increased in both subgroups of subjects, BHR+ and BHR-. The increase in V'E was
      significant in BHR- but not significant in BHR+. In general, the changes in
      V'E,fR and VT were not uniform; comparable numbers of subjects responded with
      increases (n=33) and decreases (n=30) in V'E. For fR 40 subjects responded with
      an increase and 23 with a decrease, and for VT these numbers were 26 and 37,
      respectively. The increase in FRC after histamine was significantly larger in
      BHR+ subjects than in BHR-. These findings may be interpreted to indicate that
      different mechanisms with opposite effects may be operating simultaneously, e.g.
      excitation of central inspiratory activity by stimulation of rapidly-adapting
      pulmonary stretch receptors, which will promote increases in respiratory
      frequency, tidal volume and minute ventilation, and bronchoconstriction with
      increased airway resistance, which will promote decreases in these parameters. As
      a consequence, depending on the net result of these opposite contributions to,
      e.g. minute ventilation, administration of histamine will cause an increase in
      minute ventilation in one subject and a decrease in another.

PMID- 9163649
TI  - Airway obstruction and rheumatoid arthritis.
AB  - The aim of this study was to assess the percentage of respiratory disorders and
      airway obstruction in patients with rheumatoid arthritis by comparing lung
      function test results between patients with rheumatoid arthritis and control
      subjects with other rheumatological conditions. A prospective case-control study
      of respiratory symptoms and lung function abnormalities was performed in a series
      of 100 patients with rheumatoid arthritis. Eighty eight patients with other
      rheumatological diseases served as controls. Diagnosis of respiratory disorders
      was based on clinical, radiological and spirometric findings. Airway obstruction
      was determined from predicted values. The results were compared using Student's t
      test and Chi-squared tests. An explanatory analysis was carried out by linear
      regression. The number of symptoms, respiratory disorders (including
      bronchiectasis) and lung function abnormalities was higher in patients with
      rheumatoid arthritis than in controls. After exclusion of smokers, the proportion
      of airway obstruction in patients with rheumatoid arthritis was 16% (versus 0% in
      controls), although the patients with rheumatoid arthritis still had more
      symptoms and respiratory disorders. The Chi-squared test did not identify any
      relationship between airway obstruction, duration of rheumatoid arthritis and
      type of treatment and occurrence of Sjogren's syndrome. In the nonsmokers,
      different explanatory models for the patients with and without a history of
      cardiac and respiratory disease emerged from multivariate analysis of indices of
      obstruction. These models included variables characterizing the severity and
      course of the rheumatoid arthritis. Respiratory disorders (including
      bronchiectasis) and airway obstruction are more frequent among patients with
      rheumatoid arthritis than in rheumatological controls. Although the exact
      pathophysiology of the link between bronchial obstruction and rheumatoid
      arthritis is still a matter of debate, explanatory factors for obstruction
      included variables characterizing the rheumatoid arthritis.

PMID- 9163648
TI  - Air pollution and daily admissions for chronic obstructive pulmonary disease in 6
      European cities: results from the APHEA project.
AB  - We investigated the short-term effects of air pollution on hospital admissions
      for chronic obstructive pulmonary disease (COPD) in Europe. As part of a European
      project (Air Pollution and Health, a European Approach (APHEA)), we analysed data
      from the cities of Amsterdam, Barcelona, London, Milan, Paris and Rotterdam,
      using a standardized approach to data eligibility and statistical analysis.
      Relative risks for daily COPD admissions were obtained using Poisson regression,
      controlling for: seasonal and other cycles; influenza epidemics; day of the week;
      temperature; humidity and autocorrelation. Summary effects for each pollutant
      were estimated as the mean of each city's regression coefficients weighted by the
      inverse of the variance, allowing for additional between-cities variance, as
      necessary. For all ages, the relative risks (95% confidence limits (95% CL)) for
      a 50 microg x m(-3) increase in daily mean level of pollutant (lagged 1-3 days)
      were (95% CL): sulphur dioxide 1.02 (0.98, 1.06); black smoke 1.04 (1.01, 1.06);
      total suspended particulates 1.02 (1.00, 1.05), nitrogen dioxide 1.02 (1.00,
      1.05) and ozone (8 h) 1.04 (1.02, 1.07). The results confirm that air pollution
      is associated with daily admissions for chronic obstructive pulmonary disease in
      European cities with widely varying climates. The results for particles and ozone
      are broadly consistent with those from North America, though the coefficients for
      particles are substantially smaller. Overall, the evidence points to a causal
      relationship but the mechanisms of action, exposure response relationships and
      pollutant interactions remain unclear.

PMID- 9163650
TI  - Disabling dyspnoea in patients with advanced disease: lack of effect of nebulized
      morphine.
AB  - The purpose of this placebo-controlled, double-blind, randomized study was to
      assess the effect of nebulized morphine on dyspnoea perceived at rest by patients
      with advanced disease. Seventeen hospital in-patients with disabling dyspnoea
      received isotonic saline or morphine via nebulization for 10 min through a
      mouthpiece, combined with oxygen via nasal prongs. On four consecutive days, they
      were given one of the four following treatments in random order: saline with 2 L
      x min(-1) oxygen; 10 mg morphine with 2 L x min(-1) oxygen; 20 mg morphine with 2
      L x min(-1) oxygen; and 10 mg morphine without oxygen (prongs fixed, no flow).
      Dyspnoea was assessed on a bipolar visual analogue scale (VAS) (-100% much more
      short of breath, +100% much less short of breath), and arterial oxygen saturation
      (Sa,O2) and respiratory frequency (fR) were recorded at the end of nebulization
      and 10 min later. In 14 subjects who completed the study, mean VAS ratings 10 min
      after the end of nebulization ranged +30 to +43%, with no significant difference
      between the four study days (VAS 20 mg morphine minus VAS saline, 95% confidence
      interval (95% CI) -6 to +8%). Sa,O2 significantly increased on the 3 days with
      supplemental oxygen, and remained stable on the zero flow day. Respiratory
      frequency significantly decreased on the 4 days, with a trend to correlation
      between VAS rating and parallel change in respiratory frequency (Spearman's rank
      correlation coefficient (r(s))=0.46; p=0.09). We conclude that the subjects
      benefited from saline or morphine via a placebo effect and/or a nonspecific
      effect, and that nebulized morphine had no specific effect on dyspnoea.

PMID- 9163651
TI  - Effects of inhaled versus intravenous vasodilators in experimental pulmonary
      hypertension.
AB  - Inhaled nitric oxide (NO) causes selective pulmonary vasodilation and improves
      gas exchange in acute lung failure. In experimental pulmonary hypertension, we
      compared the influence of the aerosolized vasodilatory prostaglandins (PG) PGI2
      and PGE1 on vascular tone and gas exchange to that of infused prostanoids (PGI2,
      PGE1) and inhaled NO. An increase of pulmonary artery pressure (Ppa) from 8 to
      approximately 34 mmHg was provoked by continuous infusion of U-46619 (thromboxane
      A2 (TxA2) analogue) in blood-free perfused rabbit lungs. This was accompanied by
      formation of moderate lung oedema and severe ventilation-perfusion (V'/Q')
      mismatch, with predominance of shunt flow (>50%, assessed by the multiple inert
      gas elimination technique). When standardized to reduce the Pps by approximately
      10 mmHg, inhaled NO (200 ppm), aerosolized PGI2 (4 ng x kg(-1) x min(-1)) and
      nebulized PGE1 (8 ng x kg(-1) x min(-1)) all reduced both pre- and postcapillary
      vascular resistance, but did not affect formation of lung oedema. All inhalative
      agents improved the V'/Q' mismatch and reduced shunt flow, the rank order of this
      capacity being NO > PGI2 > PGE1. In contrast, lowering of Ppa by intravascular
      administration of PGI2 and PGE1 did not improve gas exchange. "Supratherapeutic"
      doses of inhaled vasodilators in control lungs (400 ppm NO, 30 ng x kg(-1) x min(
      1) of PGI2 or PGE1) did not provoke vascular leakage or affect the physiological
      V'/Q' matching. We conclude that aerosolization of prostaglandins I2 and E1 is as
      effective as inhalation of nitric oxide in relieving pulmonary hypertension. When
      administered via this route instead of being infused intravascularly, the
      prostanoids are capable of improving ventilation-perfusion matching, suggesting
      selective vasodilation in well-ventilated lung areas.

PMID- 9163652
TI  - Chronic respiratory disease morbidity in construction workers: patterns and
      prognostic significance for permanent disability and overall mortality.
AB  - The aim of this study was to determine chronic respiratory disease morbidity in
      construction workers, and to assess the prognostic value of various morbidity
      measures on permanent disability and on all-cause mortality. Subjects in this
      analysis were male employees in the German construction industry, aged 40-64 yrs,
      who were examined by the occupational health service between August 1986 and
      December 1988. Prevalence of respiratory disorders as characterized by: 1)
      pathological findings on lung auscultation; 2) reduced forced expiratory volume
      in one second (FEV1); and 3) a medical diagnosis of chronic respiratory disease
      (International Classification of Diseases 9th revision (ICD-9) 490496) was
      assessed among occupational groups of construction workers, and compared with
      prevalence among white-collar employees. Active follow-up was conducted between
      October 1992 and July 1994 to ascertain working and life status (completeness: 92
      and 96%, respectively). The prognostic value of the morbidity measures on
      permanent disability and on all-cause mortality was assessed using the Cox
      proportional hazards model. In the entire cohort, crude prevalence was 7.6% for
      pathological findings on lung auscultation, 8.8% for a reduced FEV1 (<70% of
      predicted value), and 6.1% for a recorded diagnosis of chronic respiratory
      disease. There was strong variation of prevalence with age, smoking status and,
      less clearly, occupation. The relative risk for permanent disability varied
      between 1.9 and 3.2, and for mortality between 2.0 and 2.9, respectively, when
      men with the various measures of bronchopulmonary disorders were compared with
      other men. The morbidity measures utilized allow the identification of employees
      at higher risk of disability and death, and this may facilitate targeting of
      specific prevention and rehabilitation measures.

PMID- 9163653
TI  - Chlorine gas induced acute lung injury in isolated rabbit lung.
AB  - This study was designed to investigate the pathogenesis of chlorine gas (Cl2)
      induced acute lung injury and oedema. Isolated blood-perfused rabbit lungs were
      ventilated either with air (n=7) or air plus 500 parts per million (ppm) of Cl2
      (n=7) for 10 min. Capillary pressure, measured by analysing the pressure/time
      transients of pulmonary arterial, venous and double (both arterial and venous)
      occlusions, was unchanged in both groups. In Cl2-exposed lungs, the fluid
      filtration rate increased from -0.228+/-0.25 to 1.823+/-1.23 mL min(-1) x 100 g(
      1) (p<0.001) and the filtration coefficient increased from 0.091+/-0.01 to
      0.259+/-0.07 mL x min(-1) x cmH2O(-1) x 100 g(-1) (p<0.001). No changes were
      observed in the control lungs. The extravascular lung water/blood-free dry weight
      ratio was 8.6+/-1.6 in the Cl2 group and 4.0+/-0.5 in the control group
      (p<0.001), confirming that the increase in lung weight was related to
      accumulation of extravascular fluid. Although the alveolar flooding by oedema is
      explained, in part, by the Cl2-induced epithelial injury, our results suggest
      that Cl2 exposure induces acute lung injury and oedema due to an increased
      microvascular permeability.

PMID- 9163654
TI  - Serum and BAL Clara cell 10 kDa protein (CC10) levels and CC10-positive
      bronchiolar cells are decreased in smokers.
AB  - Cigarette smoking has diverse effects on the structure and function of the lung.
      Smoking appears to reduce the levels of Clara cell 10 kDa protein (CC10) in the
      alveolar lining fluid, but the influence of smoking serum on CC10 levels is still
      debated, and it has not been clear whether smoking reduces the number of CC10
      producing lung cells. The aims of this study were to clarify the influence of
      smoking on CC10 levels in the alveolar lining fluid and bloodstream, and on the
      number of CC10-producing lung cells. CC10 concentrations were measured in sera
      and bronchoalveolar lavage (BAL) fluids, by means of enzyme-linked immunosorbent
      assay using monoclonal and polyclonal antibody, and the immunohistochemical
      expression of CC10 was examined in the lungs of nonsmokers and smokers using the
      monoclonal antibody, TY-5, against CC10/human urinary protein-1. CC10
      concentrations in sera and in BAL fluids from healthy smokers were significantly
      lower than in healthy nonsmokers. Immunohistochemical expression of CC10 was
      found exclusively in nonciliated bronchiolar epithelial cells. As compared to
      that of nonsmokers, the mean percentage of CC10-positive bronchiolar epithelial
      cells was significantly decreased in lung tissue specimens obtained from smokers
      who had normal results in pulmonary function tests. It was concluded that smoking
      reduces the proportion of Clara cell 10 kDa protein-producing bronchiolar
      epithelial cells, resulting in decreased levels of Clara cell 10 kDa protein in
      the lower respiratory tract and in the bloodstream. The protein is a new blood
      biochemical and immunohistochemical marker, reflecting structural changes in
      peripheral airways induced by cigarette smoking.

PMID- 9163655
TI  - A longitudinal analysis of pulmonary function in rats during a 12 month cigarette
      smoke exposure.
AB  - We wanted to examine the longitudinal effects of chronic cigarette smoke
      exposure, and to determine whether the chronic alterations in pulmonary function
      induced by long-term cigarette smoke exposure in an animal model could be
      predicted by initial or early alterations in function. A group of Sprague Dawley
      rats was exposed to the smoke of 7 cigarettes x day(-1) for 5 days x week(-1)
      during a total period of 12 months. Lung volume, flow-volume curves and pressure
      volume curves were recorded at baseline, and after 2, 4, 8 and 12 months of smoke
      exposure. A control group of rats was subjected to the same regimen of testing,
      but was not exposed to smoke. Thirteen rats completed the study in the smoke
      exposed group and seven rats in the control group. We found that chronic exposure
      to cigarette smoke produced early abnormalities in pulmonary function, with the
      forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio
      showing an acceleration of ageing effect, particularly between 4 and 8 months of
      exposure. In this model, although the two groups had significantly different
      airflow after 12 months, the initial values in each group were remarkably
      similar, and we could not identify any pulmonary function test which had
      predictive value. We conclude that longitudinal studies of cigarette smoke
      exposure in this rat model allow better characterization of the nature and time
      course of the effects of smoking on the lung.

PMID- 9163656
TI  - Rapid detection of multidrug-resistant tuberculosis.
AB  - Transmission of multidrug-resistant strains of Mycobacterium tuberculosis (MDR
      TB) presents a serious problem for infection control in hospitals, particularly
      in the context of co-infection with the human immunodeficiency virus (HIV). We
      report on the use of molecular genetic tools to allow rapid assessment of samples
      from patients potentially infected with MDR-TB. Sputum and bronchoalveolar lavage
      samples were obtained from two HIV-positive patients with suspected tuberculosis,
      who had previous contact with a known MDR-TB index case. Polymerase chain
      reaction (PCR) was used directly on clinical samples to amplify genetic loci
      associated with rifampicin resistance (rpoB), and strain-specific polymorphisms
      (the direct repeat (DR) region). Drug resistance was determined using a
      commercially available kit for detection of point mutations in the rpoB gene
      (Inno-Lipa RifTB; Innogenetics, Belgium), and confirmed by nucleotide sequencing.
      Strain variation was determined using the spoligotyping method, based on the
      presence or absence of variable linker sequences within the DR region. In one
      patient, infection with a MDR strain identical to that of a known index case was
      demonstrated. A second patient, although positive for M. tuberculosis, was found
      to be infected with a rifampicin-sensitive strain. Results were obtained within
      48 h, allowing appropriate treatment to be initiated and infection control
      measures to be implemented. PCR-based tests for strain-typing and for
      identification of rifampicin resistance provide important tools for identifying
      patients with MDR-TB and for rapid monitoring of potential nosocomial spread of
      MDR-TB. Prompt confirmation or exclusion of possible transmission allows early
      clinical intervention to prevent future outbreaks of multidrug-resistant M.
      tuberculosis.

PMID- 9163657
TI  - White blood cells, C-reactive protein and erythrocyte sedimentation rate in
      pneumococcal pneumonia in children.
AB  - We evaluated the applicability of C-reactive protein (CRP), erythrocyte
      sedimentation rate (ESR), white blood cell count (WBC), and absolute neutrophil
      count (ANC), in the screening of pneumococcal (PNC) pneumonia in children. In
      1981-1982, 161 children were treated for radiologically verified community
      acquired pneumonia in the hospital during a period of 12 months. The
      Streptococcus pneumoniae aetiology of infection was studied by antigen, antibody
      and immune complex assays in acute and convalescent sera. In acute blood samples,
      CRP was measured by the immunonephelometric method, ESR by the Westergren method,
      WBC using an automatic cell counter, and thereafter the ANC was calculated after
      microscopic examination of peripheral smears. CRP and ESR were significantly
      higher in patients with alveolar (n=53) than in those with interstitial (n=108)
      pneumonia. CRP, ESR and ANC were significantly higher in PNC (n=29) than in viral
      (n=23) pneumonia. The values in mixed PNC and viral infections (n=17) were
      approximately midway between PNC and viral cases. All cases with serologic
      evidence of S. pneumoniae aetiology were combined (n=46) for calculation of
      diagnostic parameters. When a cut-off limit of 60 mg x L(-1) was used, CRP had a
      sensitivity of 26% and a specificity of 83% in the screening of PNC pneumonia. We
      conclude that C-reactive protein and erythrocyte sedimentation rate have a
      limited capacity to differentiate between pneumococcal and nonpneumococcal
      pneumonia. C-reactive protein is recommended as the first-line method of
      screening, and the value of 60 mg x L(-1) as the cut-off limit.

PMID- 9163658
TI  - Penetration of sparfloxacin and ciprofloxacin into alveolar macrophages,
      epithelial lining fluid, and polymorphonuclear leucocytes.
AB  - Sparfloxacin (SPX), a novel fluoroquinolone with a broad spectrum of
      antibacterial activity, has been shown, in vitro, to be more effective against
      common pulmonary pathogens, particularly Streptococcus pneumoniae, Mycoplasma
      pneumoniae and some intracellular organisms, than ciprofloxacin (CPX). The
      objective of this open, comparative, randomized study in two parallel groups was
      to assess the serum concentrations and penetration of SPX and CPX into alveolar
      macrophages (AMs), epithelial lining fluid (ELF), and peripheral
      polymorphonuclear leucocytes (PMNs). Patients received either a single oral dose
      of SPX, 400 mg (16 patients), or CPX, 500 mg (15 patients), at various times
      before a routine diagnostic bronchoscopy was performed. Antibiotic concentrations
      were determined by using a microbiological assay. The median serum elimination
      half-lives were 17.3 h for SPX and 5.3 h for CPX. Peak levels (median+/-68%
      confidence range) of CPX were attained in AMs (7.6+/-1.7 mg x L(-1)) at 5 h after
      admission, and in both ELF (2.13+/-0.91 mg x L(-1)) and PMNs (9.1+/-6.2 mg x L(
      1)) at 2.5 h after administration. SPX achieved comparable peak levels in PMNs
      (median+/-68% range, 9.4+/-1.1 mg x L(-1) at 5 h), but peak concentrations
      attained in AMs and ELF (35.1+/-15.4 and 32.2+/-28.2 mg x L(-1), respectively, at
      24 h) were several times higher than those of CPX. SPX demonstrated substantially
      greater accumulation in all three sites than did CPX (peak site to serum ratios
      of 11.0+/-4.3, 65.5+/-28.4 and 63.0+/-66 versus 4.94+/-0.64, 10.6+/-3.7 and
      10.6+/-3.7 for PMNs, AMs and ELF, respectively). The results indicate, that
      sparfloxacin has a long elimination half-life and that it achieves higher
      concentrations in alveolar macrophages and epithelial lining fluid than
      ciprofloxacin. Site concentrations of sparfloxacin greatly exceeded the minimal
      inhibitory concentrations of common respiratory pathogens.

PMID- 9163659
TI  - Bacterial colonization of distal airways in healthy subjects and chronic lung
      disease: a bronchoscopic study.
AB  - In contrast to the healthy population, distal airway bacterial colonization may
      occur in patients with chronic lung diseases, who often have altered pulmonary
      defences. However, the information dealing with this issue is insufficient and is
      based mainly on nonspecific samples, such as sputum cultures. Using quantitative
      cultures of bronchoscopic protected specimen brush (PSB) and bronchoalveolar
      lavage (BAL) samples, we studied the bacterial colonization of distal airways in
      16 healthy subjects, 33 patients with bronchogenic carcinoma, 18 with chronic
      obstructive pulmonary disease (COPD), 17 with bronchiectasis, and 32 with a long
      term tracheostomy due to laryngeal carcinoma. All patients were without
      exacerbation, and free from antibiotic treatment at least 1 month before the
      study protocol. Thresholds for quantitative cultures to define colonization were
      > or = 10(2) colony-forming units (cfu) x mL(-1) for PSB and > or = 10(3) cfu x
      mL(-1) for BAL. Only one healthy subject was colonized by a potential pathogenic
      microorganism (PPM) (Staphylococcus aureus 4x10(2) cfu x mL(-1) in a PSB
      culture). Colonization was observed in 14 (42%) bronchogenic carcinoma patients
      (19 non-PPMs, and 10 PPMs); in 15 (83%) COPD patients (22 non-PPMs and 7 PPMs);
      in 15 (88%) bronchiectasis patients (20 non-PPMs and 13 PPMs); and in 15 (47%)
      long-term tracheostomy patients (5 non-PPMs and 13 PPMs). The two most frequent
      non-PPMs isolated in all groups studied were Streptococcus viridans and Neisseria
      spp. Haemophilus spp., Streptococcus pneumoniae, Haemophilus influenzae, and
      Moraxella catarrhalis were the most frequent PPMs isolated in bronchogenic
      carcinoma, COPD, bronchiectasis and long-term tracheostomized patients,
      respectively. Pseudomonas aeruginosa colonization was infrequent in all the
      groups. Our results show that distal airway bacterial colonization is a frequent
      feature in stable patients with chronic lung diseases and also in patients with
      long-term tracheostomy. However, the pattern of colonization differs among groups
      studied. The knowledge of different colonization patterns may be important for
      future antibiotic prophylactic strategies and for the empirical antibiotic
      regimens when exacerbations occur in these patients.

PMID- 9163660
TI  - Nasal potential difference in cystic fibrosis patients presenting borderline
      sweat test.
AB  - The diagnosis of cystic fibrosis (CF) can be difficult if the sweat test and
      routine deoxyribonucleic acid (DNA) analysis are inconclusive. Under these
      circumstances, measurement of nasal potential difference (NPD) was proposed as a
      complementary diagnostic tool, as demonstrated in subjects bearing the G551S or
      3849+10KbC-->T mutations. The purpose of the present study was to verify the
      diagnostic value of this technique in CF patients with a borderline sweat test.
      NPD was measured in 18 patients with a borderline sweat test, in whom CF
      diagnosis was based on the presence of one CF gene mutation in each chromosome
      (CF borderline). These patients were compared both to non-CF controls and CF
      patients with an abnormal sweat test (CF controls). Basal NPD values of CF
      borderline patients (mean value -39+/-6 mV, range -29 to -52 mV; n=18) were in
      the pathological range of CF controls (-39+/-8 mV, range -28 to -57 mV; n=37),
      and both were statistically different from values obtained in non-CF controls (
      15+/-4 mV, range -6 to -23 mV; n=24; p<0.0001). Mutation analysis confirmed a
      high frequency of the 3849+10KbC-->T mutation in this group of CF borderline
      patients (positive in 14 out of 18 subjects), whereas other mutations, such as
      AF508, Q552X, N1303K and R1162X, were also found to be associated with this
      atypical CF phenotype. These results confirm the presence of pathological values
      of basal NPD in CF patients with borderline sweat test, and also extend this
      finding to subjects bearing genotypes other than the G551S and 3849+10KbC-->T
      mutations. The present findings, therefore, confirm the usefulness of measurement
      of basal nasal potential difference in all those patients in whom diagnosis of
      cystic fibrosis can be suspected but the sweat test remains inconclusive.

PMID- 9163661
TI  - Parapneumonic effusion and empyema.
AB  - Parapneumonic effusions account for about one third of all pleural effusions.
      Approximately 40% of patients with pneumonia develop a concomitant effusion,
      which is associated with an increased morbidity and mortality. In order to select
      the most appropriate therapy for the individual patient, the effusion should be
      categorized as being in the exudative, fibropurulent, or organizational stage,
      and all necessary information should be compiled to decide whether the effusion
      is likely to take an uncomplicated or a complicated course. There is a
      considerable variation in the aggressiveness and course of parapneumonic
      effusions, and, therefore, the spectrum of the appropriate therapy may vary from
      a conservative approach in uncomplicated effusions to aggressive surgical
      intervention in advanced multiloculated empyemas. This review discusses current
      diagnostic and therapeutic options and offers guidelines for treating the various
      stages of parapneumonic effusions and empyemas.

PMID- 9163662
TI  - Chylothorax and pseudochylothorax.
AB  - Chylothorax is the occurrence of chylus (lymph) in the pleura due to damage to
      the thoracic duct. There is a high content of triglycerides, and chylomicrons can
      be seen. It is usually right-sided, since most of the duct is within the right
      hemithorax. With damage at the level of the aorta, the chyle will appear on the
      left. Traumatic rupture occurs after accidents or surgery. Of nontraumatic
      causes, the most common is a malignant lymphoma. Computed tomography (CT) scan of
      the thorax and upper abdomen should be performed. Lymphography can show where the
      leakage or blockage is situated. With repeated drains, large amounts of fat,
      proteins, and lymphocytes are lost. Treatment is with low-fat diet or parenteral
      nutrition to decrease the amount of chyle, but chemical pleurodesis or ligation
      of the thoracic duct, usually via thoracoscopy, is often necessary.
      Pseudochylothorax (cholesterol pleurisy) occurs with long-standing fluid in a
      fibrotic pleura. The fluid has a high content of cholesterol but no triglycerides
      or chylomicrons. In both conditions, the pleural fluid is thick, opalescent,
      whitish or the colour of cafe-au-lait.

PMID- 9163663
TI  - Comparison of guidelines and self-management plans in asthma.
AB  - Since the rise in asthma mortality and morbidity, many guidelines and self
      management plans have been published. Many of these guidelines and self
      management plans are not, however, based on results of previous studies but on
      the opinion of experts. We compared the five most frequently cited asthma
      guidelines concerning treatment steps and self-management plans with special
      regard to peak expiratory flow (PEF)-guided plans in asthma. We also compared
      results of published studies with asthma-management in the context of the
      guidelines. Classification of asthma severity differed considerably between the
      guidelines. This was also true for PEF-guided patient self-management plans.
      Although there was agreement on the type of drug to be used, guidelines varied
      with respect to when to use the drug, the "best" strategy to increase the dose,
      and the maximum dose. The studies available on self-management do not make it
      possible to determine which part of the programme is most important or cost
      effective. The latter is an important issue.

PMID- 9163664
TI  - Bronchial vascular congestion and angiogenesis.
AB  - The bronchial vasculature is the systemic arterial blood supply to the lung.
      Although small relative to the pulmonary blood flow, the bronchial vasculature
      serves important functions and is modified in a variety of pulmonary and airway
      diseases. Congestion of the bronchial vasculature may narrow the airway lumen in
      inflammatory airway diseases, and formation of new bronchial vessels
      (angiogenesis) is implicated in the pathology of a variety of chronic
      inflammatory, infectious and ischaemic pulmonary diseases. The remarkable ability
      of the bronchial vasculature to remodel has implications for disease
      pathogenesis. The contributions of the bronchial vasculature to the pathogenesis
      of pulmonary disease are reviewed in this article.

PMID- 9163665
TI  - Bronchial Kaposi's sarcoma after single lung transplantation.
AB  - Kaposi's sarcoma (KS) has been reported in 6% of malignancies of solid organ
      transplant recipients. Most of the observations have been in recipients of renal
      allografts but, so far, KS has not been described in lung transplantation. We
      report a case of bronchial KS occurring in a black patient 6 months after single
      lung-transplantation. Skin lesions were absent and, interestingly, KS lesions
      were observed solely in the trachea and the native lung. Following reduction of
      the immunosuppressive regimen a complete remission was obtained 1 year later. Up
      to the present time, this clinical remission is very encouraging, but close
      surveillance remains necessary to detect rejection episodes or the reappearance
      of KS following manipulation of the immunosuppressive therapy.

PMID- 9163666
TI  - Pneumocystis carinii pneumonia in a HIV-seronegative patient with untreated
      rheumatoid arthritis and CD4+ T-lymphocytopenia.
AB  - Pneumocystis carinii pneumonia (PCP) usually occurs in immunocompromised
      patients, and it is a life-threatening infection. We report the case of a human
      immunodeficiency virus (HIV)-seronegative patient with untreated rheumatoid
      arthritis (RA), who developed fatal PCP related to uncommon CD4+ T
      lymphocytopenia. Although extremely rare and of uncertain aetiology, suppression
      of cellular immunity and subsequent opportunistic infections should be suspected
      in such patients.

PMID- 9163667
TI  - Bronchiolitis obliterans organizing pneumonia in three children with acute
      leukaemias treated with cytosine arabinoside and anthracyclines.
AB  - Bronchiolitis obliterans organizing pneumonia (BOOP) is a clinicopathological
      entity with well-defined diagnostic criteria, which can be idiopathic or produced
      by a variety of biological processes. We describe the occurrence of BOOP in three
      children, one with acute lymphoblastic leukaemia and two with acute promyelocytic
      leukaemia. In the three patients, BOOP developed 10-20 days after a course of
      therapy with cytosine arabinoside and anthracyclines. The possible relationships
      between the small conducting airway lesions, lung toxic reaction to the drugs
      and/or nonidentified infectious agents are discussed.

PMID- 9163668
TI  - Chronic thromboembolic pulmonary hypertension and vascular transformation of the
      lymph node sinuses.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease often not
      recognized until it is far advanced. Medical management does not reverse the
      effects of the disease, nor does it prevent its progression. Pulmonary
      thromboendarterectomy is the preferred treatment. We present the case of a
      patient in whom CTEPH was mistaken for an interstitial lung disease with
      mediastinal lymph node enlargement. The mediastinal lymph node enlargement was
      due to vascular transformation of the lymph node sinuses (VTS). This is an
      unusual case of chronic thromboembolic pulmonary hypertension with vascular
      transformation of the lymph node sinuses.

PMID- 9163669
TI  - Clinical prediction rules in obstructive sleep apnoea syndrome.

PMID- 9163670
TI  - Genetic and epigenetic aspects of DNA methylation on genome expression,
      evolution, mutation and carcinogenesis.

PMID- 9163671
TI  - Progression of PDMT is accompanied by lack of Fas and intense expression of Bcl-2
      and PKC-epsilon.
AB  - Recent study has demonstrated the development of pregnancy-dependent mammary
      tumors (PDMTs) in GR/A mice during pregnancy and their regression by apoptotic
      cell death after parturition. In the present study, we examined the molecular
      machinery of PDMTs before and after parturition and in progression. The death
      associated-cell surface molecule Fas was expressed only when apoptosis occurred,
      and no expression could be determined after progression. Interestingly, death
      suppressor Bcl-2 showed down-regulation when apoptosis occurred, and intense
      expression after progression. Examination of the possible involvement of PKC
      isozymes showed that only PKC-epsilon showed drastic changes in expression:
      expression was not detected in normal mammary gland cells and PDMTs, but was
      instead seen only when PDMTs progressed to malignant tumors. On the basis of
      these results, we suggest that PDMT-regression is due to Fas-mediated apoptosis,
      and that lack of Fas, persistent expression of Bcl-2, and new expression of PKC
      epsilon are essential events for tumor progression.

PMID- 9163672
TI  - Alkylation-induced apoptosis of embryonic stem cells in which the gene for DNA
      repair, methyltransferase, had been disrupted by gene targeting.
AB  - An enzyme O6-methylguanine-DNA methyltransferase (MGMT) catalyzes transfer of a
      methyl group from O6-methylguanine and O4-methylthymine of alkylated DNA to its
      own molecule, thereby repairing the pre-mutagenic lesions in a single step
      reaction. Making use of gene targeting, we developed mouse embryonic stem (ES)
      cell lines deficient in the methyltransferase. Quantitative immunoblot analysis
      and enzyme assay revealed that MGMT-/- cells, in which both alleles were
      disrupted, contained no methyltransferase protein while cells with one intact
      allele (MGMT+/-) contained about half the amount of protein carried by the
      parental MGMT+/+ cells. MGMT-/- cells have an extremely high degree of
      sensitivity to simple alkylating agents, N-methyl-N'-nitro-N-nitrosoguanidine
      (MNNG) and N-methyl-N-nitrosourea (MNU), whereas MGMT+/- cells are slightly more
      sensitive to these agents, as compared with findings from normal cells. A high
      frequency of mutation was induced in MGMT-/- cells on exposure to a relatively
      low dose of MNNG. Electrophoretic analyses of the DNAs as well as fluorochrome
      staining of the cells revealed that MGMT-/- cells treated with MNNG undergo
      apoptotic death, which occurs after G2-M arrest in the second cycle of cell
      proliferation.

PMID- 9163673
TI  - The role of UV-B light in skin carcinogenesis through the analysis of p53
      mutations in squamous cell carcinomas of hairless mice.
AB  - Mutation spectra of the p53 gene from human skin carcinomas have been connected
      to solar UV radiation. For comparison we have characterized the mutation spectrum
      of the p53 gene in a very large sample of squamous cell carcinomas from hairless
      mice induced with UV of wavelength 280-320 nm (UV-B), which have substantiated
      the mutagenic effects of UV-B radiation in vivo. Tumors from hairless mice,
      random bred SKH:HR1 as well as inbred SKH:HRA strains, which are analyzed for
      mutations in the conserved domains of the p53 protein present a very specific
      mutation spectrum. The observed mutation frequency after chronic UV-B radiation
      in the p53 gene ranged from 54% (SKH-HRA) to 73% (SKH-HR1) among the 160 tumors
      analyzed. Over 95% of the mutations were found at dipyrimidine sites located in
      the non-transcribed strand, the majority were C-->T transitions and 5% were CC-
      >TT tandem double mutations. Four distinct UV-B mutation hot spots have been
      identified for the first time: two major ones at codons 267 (33%) and 272 (19%)
      and two minor ones at codons 146 (10%) and 173 (4%). The codon 267 hot spot
      consists of a CpG preceded by a pyrimidine, which confirms in vivo an important
      role for this UV-B mutable site in UV-B-induced skin tumors that is not found in
      other types of mouse tumors. Comparison with mutation spectra from human skin
      carcinomas fully validates the merits of the hairless mouse model for studying
      the molecular mechanisms of skin carcinogenesis. For example, the murine hot spot
      at codon 272 does have a full equivalent in human skin carcinomas. In contrast,
      the human equivalent of the murine codon 267 lacks the dipyrimidine site and
      therefore fails to be a pronounced hot spot in human skin carcinomas; however,
      this site is one of the major hot spots in human internal cancers (evidently not
      induced by UV radiation but probably by deamination of the 5 methyl cytosine).

PMID- 9163674
TI  - In vitro activation of the human Harvey-ras proto-oncogene by aflatoxin B1.
AB  - Activation of ras proto-oncogenes occurs frequently in vivo in chemically induced
      rodent tumours, including rat hepatomas induced by aflatoxin B1. This study
      examines the in vitro activation of a human ras gene by this mycotoxin. A plasmid
      containing the human Ha-ras proto-oncogene, together with a neomycin resistance
      gene (pECneo), was incubated in vitro with a microsomal system generating
      aflatoxin B1 8,9-epoxide. Subsequent transfection of the plasmid into mouse NIH
      3T3 fibroblasts, followed by G418 selection and s.c. injection of surviving cells
      into immunodeficient mice demonstrated that the proto-oncogene had acquired
      transforming capacity. Although a single tumour resulted from similar treatment
      of incubated unconjugated plasmid, no tumours were produced by a secondary round
      of transfections using DNA from this tumour. Selective PCR amplification of the
      human Ha-ras gene in extracted tumour DNA followed by sequencing demonstrated the
      presence of G-->T transversions either at the first or middle base of codon 12 in
      tumours resulting from transfection with the aflatoxin-B1-modified pECneo
      plasmid, but this was not detected in the single tumour resulting from
      transfection with the unmodified plasmid. Thus, although a mutation in the Ha-ras
      gene has not been reported for human primary hepatomas occurring in aflatoxin
      exposed populations, metabolically activated aflatoxin B1 is capable of mutating
      this proto-oncogene to its oncogenic form in vitro. No mutations were observed in
      codon 61. It appears that, in contrast to the frequently reported G-->T
      transversions in codon 249 of the p53 gene in primary hepatomas in aflatoxin
      exposed humans, the failure to detect Ha-ras mutations in these tumours is not
      due to an inability of aflatoxin B1 to activate this proto-oncogene. The G-->T
      transversions observed in this study contrast with the most frequent aflatoxin B1
      in vivo induced mutations, G-->A transitions in the rat Ki-ras gene. Possible
      mechanisms for these differences are discussed.

PMID- 9163675
TI  - EGF- and CPA-induced mitogenic stimuli are differentially down-regulated by TGF
      beta1 in cultured rat hepatocytes.
AB  - Down-regulation of the mitogenic activity of the rodent liver carcinogen
      cyproterone acetate (CPA) and of epidermal growth factor (EGF) were compared in
      cultured rat hepatocytes. Both hepatomitogens produce an increase in the
      expression of proliferating cell nuclear antigen (PCNA) and in [3H]thymidine
      incorporation in a dose-dependent manner. In combination, the two mitogens
      induced an additive mitogenic response. Concomitant exposure to the growth
      inhibitory cytokine transforming growth factor beta1 (TGF-beta1) resulted in a
      differential dose-dependent down-regulation of PCNA-expressing cells. The
      corresponding down-regulation of CPA-induced PCNA expression required a 3- to 5
      fold higher TGF-beta1 concentration than for EGF-induced expression. In contrast,
      CPA-exposed hepatocytes become vulnerable to and EGF-exposed cells protected
      against the apoptosis-inducing activity of TGF-beta1 (>0.1 ng/ml). Under culture
      conditions that mimicked a pericentral-equivalent microenvironment (low oxygen
      tension, low glucagon concentration), PCNA expression was 3-fold lower and CPA
      specific resistance was no longer detectable. It is concluded that EGF and CPA
      induce their growth stimuli preferentially in the periportal area of the liver
      but in different hepatocyte sub-populations, which differ in their down
      regulation of premitotic events by TGF-beta1. At low TGF-beta1 concentrations,
      EGF-stimulated cells shift back into a resting cell cycle phase, whereas CPA
      treated hepatocytes are eliminated by apoptosis at higher TGF-beta1
      concentrations.

PMID- 9163676
TI  - Mammalian DNA repair methyltransferases shield O4MeT from nucleotide excision
      repair.
AB  - O6-Methylguanine (O6MeG) and O4-methylthymine (O4MeT) are potentially mutagenic
      DNA lesions that cause G:C-->A:T and A:T-->G:C transition mutations by mispairing
      during DNA replication, and the repair of O6MeG and O4MeT by DNA repair
      methyltransferases (MTases) is therefore expected to prevent methylation-induced
      transitions. The efficiency of O6MeG and O4MeT repair by different MTases can
      vary by several hundred-fold and the aim of this study was to establish the
      biological consequences of such differences in the efficiency of repair. The
      ability of three microbial and two mammalian MTases to prevent methylation
      induced G:C-->A:T and A:T-->G:C transitions is taken as a measure of their
      ability to repair O6MeG and O4MeT in vivo respectively. All five MTases give
      complete protection against G:C-->A:T transitions. However, while the microbial
      MTases give complete protection against A:T-->G:C transitions, the mammalian
      MTases actually sensitize cells to A:T-->G:C transitions. We hypothesize that the
      mammalian MTases bind O4MeT lesions in vivo but that, because they are extremely
      slow at subsequent methyl transfer, binding shields O4MeT from repair by the
      nucleotide excision repair pathway. Results are presented to support this
      hypothesis.

PMID- 9163677
TI  - Mechanism of inhibition of MDA-MB-468 breast cancer cell growth by 2,3,7,8
      tetrachlorodibenzo-p-dioxin.
AB  - Treatment of estrogen receptor (ER)-negative MDA-MB-468 human breast cancer cells
      with 10 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced formation of a
      nuclear aryl hydrocarbon (Ah) receptor complex as determined by ligand-binding
      and gel electrophoretic mobility shift assays. TCDD also induced CYP1A1-dependent
      activity in MDA-MB-468 cells, which represents the first ER-negative Ah receptor
      positive human breast cancer cell line that has been identified. Treatment of
      this cell line with TCDD and related compounds also caused a 50% inhibition of
      cell growth, which resembled the growth inhibitory effects previously reported
      for epidermal growth factor (EGF). However, EGF expression is minimal in this
      cell line and is not induced by TCDD; moreover, EGF and TCDD induced a different
      pattern of oncogene expression and apoptosis in MDA-MB-468 cells. In contrast,
      TCDD caused a rapid and sustained induction of transforming growth factor alpha
      (TGF alpha) gene expression and secreted protein (nearly 2-fold); moreover, the
      growth-inhibitory effects of TCDD could be blocked by antibodies to the EGF
      receptor. In a separate experiment, it was shown that TGF alpha also inhibited
      growth of MDA-MB-468 cells. The results of this study indicate that the mechanism
      of growth inhibition of MDA-MB-468 cells by TCDD is due to induction of TGF
      alpha, which is a potent antimitogen in this cell breast cancer line.

PMID- 9163678
TI  - Time course comparison of cell-cycle protein expression following partial
      hepatectomy and WY14,643-induced hepatic cell proliferation in F344 rats.
AB  - During recent years, there has been an extensive research focus in the area of
      cell-cycle control in eukaryotes and the relationship that exists between cell
      proliferation and cancer. The eukaryotic cell-cycle is governed by signal
      transduction pathways mediated by complexes of cyclin dependent kinases (CDK) and
      their partner cyclin proteins. This study was performed to identify differences
      in cell-cycle control protein expression following physical and chemical stimuli
      of hepatic cell growth. Protein levels of cell cycle mediators, cyclin dependent
      kinases (CDK 1,2,4,5), cyclin proteins (A,B,D1-D3 and E), proliferating cell
      nuclear antigen (PCNA), tumor suppressor proteins (p53 and Rb), and CDK
      inhibitory proteins (p16Ink4, p21Waf1 and p27Kip1) were examined in F344 rats
      following 70% partial hepatectomy or a single dose of WY14,643 over 96- and 48-h
      time courses, respectively. CDK1 (p34cdc2) and PCNA protein concentrations,
      quantified by ELISA, were significantly increased beginning at the 24-h time
      point and maximal at 48 h (6.9- and 3.7-fold for partial hepatectomy and 4.2- and
      3.3-fold for WY14,643, respectively). Differential effects were observed with the
      G1 cell-cycle mediators CDK4, CDK5, and cyclin D3, p21Waf1 and p27Kip1 CDK
      inhibitory protein concentrations rose in accordance with the induction of DNA
      synthesis and histone H1 kinase activity. In addition, there were dramatic
      differences in p53 protein expression patterns following partial hepatectomy
      versus WY14,643 dosing. Because non-genotoxic hepatocarcinogens are known to
      induce cellular proliferation, data generated from this study may aid in
      elucidating the specific hepatocarcinogenic signal transduction pathways
      stimulated by non-genotoxic carcinogens.

PMID- 9163679
TI  - Role of antioxidants and intracellular free radicals in retinamide-induced cell
      death.
AB  - The cancer chemopreventive synthetic retinoid N-(4-hydroxyphenyl)retinamide (HPR)
      possesses antiproliferative and apoptotic activity at pharmacological doses. In
      this study we show that addition of antioxidants to HL-60 cells cultured in the
      presence of 3 microM HPR, markedly suppresses the apoptopic effect of the
      retinoid and significantly prolongs cell survival (48-96 h). We also show, by the
      use of the oxidation-sensitive probe 2',7'-dichlorofluorescin diacetate (DCF-DA)
      and in combination with flow cytometric and spectrofluorimetric analysis, that
      treatment of cells with 3 microM HPR results in an immediate and sustained
      production of intracellular free radicals, most likely hydroperoxides.
      Interestingly, the formation of these HPR-induced free radicals is effectively
      blocked by the water soluble antioxidants L-ascorbic acid and N-acetyl-L
      cysteine. Neither 3-15 microM N-(4-methoxyphenyl) retinamide (MPR), the
      structurally similar but biologically inert analog of HPR, nor 3 microM doses of
      the retinoids all-trans retinoic acid, 9-cis-retinoic acid, TTNPB and SR11237
      induce intracellular free radicals, thus indicating that the specificity of this
      phenomenon is restricted to HPR. Altogether, we provide the first direct evidence
      that HPR stimulates the generation of intracellular free radicals, which appear
      to have a causative role in the induction of apoptosis in vitro. Our findings
      raise the possibility that the therapeutic efficacy of HPR may, at least in part,
      depend on these apoptosis-inducing oxidative phenomena.

PMID- 9163680
TI  - Inhibitory effects of lemon grass (Cymbopogon citratus Stapf) on formation of
      azoxymethane-induced DNA adducts and aberrant crypt foci in the rat colon.
AB  - The 80%-ethanol extract of lemon grass (Cymbopogon citratus Stapf), a medicinal
      plant in Thailand, has been reported to be antimutagenic against various known
      mutagens in the Salmonella mutation assay. To investigate chemoprevention in an
      animal carcinogenesis model, we examined inhibitory effects of the lemon grass
      extract on the formation of azoxymethane (AOM)-induced DNA adducts and aberrant
      crypt foci (ACF) in the rat colon. One week after the start of the treatment with
      lemon grass extract at doses of 0.5 or 5 g/kg body wt by gavage, F344 rats
      received two s.c. injections of 15 mg of AOM per kg body weight at 1 week apart.
      For DNA adduct analysis of the colon and liver, the rats were killed 12 h after
      the second AOM injection. The DNA from the liver and colon were used for O6
      methylguanine and N7-methylguanine analysis. For ACF analysis in the initiation
      stage, AOM-injected rats were continuously treated with lemon grass extract and
      were killed 3 weeks after the second AOM injection. For analysis in the promotion
      stage the treatment with the lemon grass extract (0.5 g/kg) started 2 weeks after
      the second AOM injection and continued for 12 weeks until the animals were
      killed. Lemon grass treatment significantly inhibited DNA adduct formation in
      both the colonic mucosa and the muscular layer but not in the liver. In addition,
      lemon grass extract treatment significantly inhibited ACF formation in both the
      initiation stage and the promotion stage. Especially in the promotion stage,
      lemon grass treatment inhibited the formation of larger ACF (with four or more
      crypts per focus), which was predictive of tumor incidence. Furthermore, lemon
      grass extract inhibited fecal beta-glucuronidase competitively and had
      antioxidant activity. These results suggest that the lemon grass extract inhibits
      the release of activated aglycon, methylazoxymethanol, from a glucuronide
      conjugate in the colon, and decreases the DNA adducts and ACF formation in the
      rat colon.

PMID- 9163681
TI  - Chemoprevention of azoxymethane-induced rat colon carcinogenesis by the naturally
      occurring flavonoids, diosmin and hesperidin.
AB  - The modulating effects of dietary feeding of two flavonoids, diosmin and
      hesperidin, both alone and in combination, during the initiation and post
      initiation phases on colon carcinogenesis initiated with azoxymethane (AOM), were
      investigated in male F344 rats. Animals were initiated with AOM by weekly s.c.
      injections of 15 mg/kg body wt for 3 weeks to induced colon neoplasms. Rats were
      fed the diets containing diosmin (1000 ppm), hesperidin (1000 ppm) or diosmin
      (900 ppm) + hesperidin (100 ppm) for 5 weeks (initiation treatment) or 28 weeks
      (post-initiation treatment). The others contained the groups of rats treated with
      diosmin, hesperidin alone or in combination, and untreated. At the end of the
      study (32 weeks), the incidence and multiplicity of neoplasms (adenoma and
      adenocarcinoma) in the large intestine of rats initiated with AOM together with,
      or followed by, a diet containing diosmin or hesperidin were significantly
      smaller than those of rats given AOM alone (P <0.001). The combination regimen
      during the initiation and post-initiation stages also inhibited the development
      of colonic neoplasms, but the tumor data did not indicate any beneficial effect
      of diosmin and hesperidin administered together as compared with when these
      agents were given individually. In addition, feeding of diosmin and hesperidin,
      both alone and in combination, significantly inhibited the development of
      aberrant crypt foci. As for cell proliferation biomarkers, dietary exposure of
      diosmin and hesperidin significantly decreased the 5'-bromodeoxyuridine-labeling
      index and argyrophilic nuclear organizer region's number in crypt cells, colonic
      mucosal ornithine decarboxylase activity, and polyamine levels in the blood.
      These results indicate that diosmin and hesperidin, both alone and in
      combination, act as a chemopreventive agent against colon carcinogenesis, and
      such effects may be partly due to suppression of cell proliferation in the
      colonic crypts, although precise mechanisms should be clarified.

PMID- 9163682
TI  - Associations between cytochrome P4502E1 genotype, mutagen sensitivity, cigarette
      smoking and susceptibility to lung cancer.
AB  - Cytochrome P4502E1 (CYP2E1) is involved in the metabolic activation of
      carcinogenic N-nitrosoamines. We therefore assessed the genotype frequencies of
      PstI or RsaI CYP2E1 restriction fragment length polymorphisms and another
      susceptibility marker, mutagen sensitivity, in 137 lung cancer cases (92 African
      American and 45 Mexican American) and 206 controls (114 African American and 92
      Mexican American) identified in a molecular epidemiological study of lung cancer.
      The CYP2E1 c1/c1 genotype was found in 86.7% of Mexican American cases, 70.6% of
      Mexican American controls, 89.1% of African American cases and 86.8% of African
      American controls. By multivariate analysis, this genotype was found to be
      associated with a 14.0-fold increased risk of lung cancer in Mexican Americans
      but not in African Americans; a 9.9-fold increased risk of lung cancer in Mexican
      American former smokers, but not in non-smokers or current smokers; a 15-fold
      increased risk of lung cancer in Mexican American males, but not in females.
      Patients with the susceptible genotype appeared to have developed cancer at an
      earlier age and with lower cigarette pack-year of exposure than did patients with
      the c1/c2 or c2/c2 genotypes. Stratified analysis suggested a greater than
      multiplicative interaction between cigarette smoking and CYP2E1 c1/c1 genotype,
      although not statistically significant. The odds ratios (ORs) for the CYP2E1
      c1/c1 genotype, cigarette smoking and both risk factors combined were 1.3, 6.7
      and 16.3, respectively. The association between CYP2E1 c1/c1 genotype and pack
      years of smoking followed the same pattern. The interaction between mutagen
      sensitivity and CYP2E1 c1/c1 genotype was especially strong in former smokers
      (the ORs for the CYP2E1 c1/c1 genotype, mutagen sensitivity and both risk factors
      combined were 3.9, 5.4 and 23.0, respectively). Therefore, the data suggest that
      individuals who lack a c2 allele might be at higher risk for developing lung
      cancer.

PMID- 9163683
TI  - Use of E mu-PIM-1 transgenic mice short-term in vivo carcinogenicity testing:
      lymphoma induction by benzo[a]pyrene, but not by TPA.
AB  - E mu-pim-1 transgenic mice are predisposed to develop lymphomas. Due to their low
      spontaneous tumour incidence and their increased sensitivity towards the
      lymphomagen ethylnitrosourea these mice may present an interesting model for
      short-term carcinogenicity testing. Here, we report on the further exploration of
      this transgenic mouse model with two additional carcinogens known to have, among
      others, the lymphohaematopoietic system as target, i.e. benzo[a]pyrene (B[a]P)
      and 12-O-tetradecanoylphorbol-13-acetate (TPA). B[a]P, given three times a week
      (by gavage) for 13 weeks at 4.3, 13 or 39 mg/kg body weight, resulted in a dose
      related increase in lymphomas up to a 90% incidence in E(mu)-pim-1 mice during
      the observation period of 40 weeks. B[a]P also induced tumours of the forestomach
      within this observation period, though at a lower incidence and apparently
      equally effective in wildtype and transgenic mice. TPA, on the other hand, was
      unable to induce lymphomas (or tumours in any other organ) in either transgenic
      or wildtype animals within the observation period of 44 weeks, when applied
      dermally at the maximum tolerated dose of 3 microg/mouse, twice a week for 35
      weeks. Molecular analysis showed that B[a]P-induced lymphomas in transgenic mice
      were of T-cell origin, 80% of which had elevated levels of c-myc expression. None
      of the lymphomas had increased N-myc expression and mutation analysis of the ras
      gene family revealed a K-ras mutation in only one out of eight tumours
      investigated. Also, none of the lymphomas showed aberrant expression of p53 as
      determined by immunohistochemistry. It is concluded that the E mu-pim-1 mouse
      model will not be very suitable for short-term carcinogenicity testing in
      general: only genotoxic chemicals that have the lymphohaematopoietic system as
      target for carcinogenesis in wild-type mice, appear to be efficiently identified.

PMID- 9163684
TI  - Urinary mutagenicity as a biomarker in workers exposed to benzidine: correlation
      with urinary metabolites and urothelial DNA adducts.
AB  - Urinary mutagenicity has been used in occupational and epidemiological studies
      for over two decades as a cost-effective, general biomarker of exposure to
      genotoxic agents. However, few studies have compared urinary mutagenicity to
      additional biomarkers determined among low- and high-exposed groups. To address
      this issue, we evaluated the relationship between urinary mutagenicity and other
      types of biomarkers in a cross-sectional study involving 15 workers exposed to
      the urinary bladder carcinogen benzidine (BZ, high exposure), 15 workers exposed
      to BZ-dyes (low exposure), and 13 unexposed controls in Ahmedabad, India. Urinary
      organics were extracted by C18/methanol and evaluated for mutagenicity in the
      presence of S9 in the Salmonella strain YG1024, which is a frameshift strain that
      overproduces acetyltransferase. The results were compared to biomarker data
      reported recently from the same urine samples (Rothman et al., Proc. Natl Acad.
      Sci. USA, 93, 5084-5089, 1996) that included a metabolite biomarker (the sum of
      the urinary levels of BZ + N-acetylbenzidine + N,N'-diacetylbenzidine) and a DNA
      adduct biomarker [a presumptive N-(3'-phosphodeoxyguanosin-8-yl)-N'
      acetylbenzidine (C8dG-ABZ) DNA adduct in exfoliated urothelial cells]. The mean
      +/- SE urinary mutagenicity (revertants/micromol of creatinine) of the low
      exposure (BZ-dye) workers was 8.2 +/- 2.4, which was significantly different from
      the mean of the controls (2.8 +/- 0.7, P = 0.04) as was that of the mean of the
      high-exposure (BZ) workers (123.2 +/- 26.1, P < 0.0001). Urinary mutagenicity
      showed strong, positive correlations with urinary metabolites (r = 0.88, P <
      0.0001) and the level of the presumptive C8dG-ABZ urothelial DNA adduct (r =
      0.59, P = 0.0006). A strong association was found between tobacco use (bidi
      smoking) and urinary mutagenicity among the controls (r = 0.68, P = 0.01) but not
      among the exposed workers (r = 0.18, P = 0.11). This study confirms the ability
      of a biomarker such as urinary mutagenicity to detect low-dose exposures,
      identify additional genotoxic exposures among the controls, and correlate
      strongly with urinary metabolites and DNA adducts in the target tissue (urinary
      bladder epithelia) in humans.

PMID- 9163685
TI  - Chemoprevention of spontaneous tumorigenesis in nullizygous p53-deficient mice by
      dehydroepiandrosterone and its analog 16alpha-fluoro-5-androsten-17-one.
AB  - Transgenic mice with both alleles of the p53 tumor suppressor gene product
      'knocked out' by gene targeting are susceptible to early development of tumors,
      chiefly lymphomas and sarcomas. Compared with the control group, administration
      of dehydroepiandrosterone (DHEA) at 0.3% of the diet to male p53-deficient mice
      extended their lifespan by delaying death due to neoplasms (from 105 to 166 days
      on study, P = 0.002), primarily by suppressing lymphoblastic lymphoma (from 45 to
      6% of neoplastic deaths, P = 0.010). Treatment with a synthetic DHEA analog,
      16alpha-fluoro-5-androsten-17-one (compound 8354), at 0.15% of the diet also
      increased lifespan, to 140 days for mice that developed tumors (P = 0.037). The
      effects of these steroids on lifespan and tumor development did not appear to be
      strongly related to inhibition of food consumption and weight gain, in that a
      group pair-fed with control diet to the reduced food consumption of the DHEA
      treated group developed and died of the same types of neoplasms at the same rate
      as the controls fed ad libitum. The chemopreventive effect of these steroids has
      been proposed to be due to suppression of DNA synthesis by inhibition of glucose
      6-phosphate dehydrogenase, the rate-limiting enzyme of the pentose phosphate
      pathway. Although DHEA and its analog are strong non-competitive inhibitors of
      this enzyme in vitro, treatment with DHEA did not deplete cellular nucleotide
      pools in the liver, as would have been predicted. The chemopreventive effect of
      DHEA in this model may be due to steroid-induced thymic atrophy and suppression
      of T cell lymphoma, permitting these mice to survive long enough to develop
      tumors with longer latency.

PMID- 9163686
TI  - Induced hyperproliferation in epithelial cells of mouse prostate by a Western
      style diet.
AB  - In this study the effects of a Western-style diet on epithelial cell
      proliferation in the prostate and bladder of C57BL/6J mice were investigated. The
      Western-style diet contained increased fat and low calcium and vitamin D,
      compared with AIN-76A control diet, at levels simulating human Western diets
      based on nutrient density. After feeding the Western-style and AIN-76A diets for
      5 and 16 weeks, mice were infused with bromodeoxyuridine (BrdU) for 72 h using
      s.c. implanted osmotic pumps. Findings revealed that in bladder epithelium BrdU
      labeling indices were not significantly different (P > 0.05) between mice on the
      control and Western-style diets at both time periods. However, significant
      increases in BrdU labeling indices occurred in epithelial cells of the anterior
      (P = 0.024) and dorsal (P = 0.049) lobes, but not in the ventral lobe (P = 0.21),
      of the mouse prostate after feeding the Western-style diet for 16 weeks, compared
      with mice on the control diet. These findings demonstrate Western-style diet
      induction of epithelial cell hyperproliferation in anterior and dorsal lobes of
      the mouse prostate. The findings further suggest that these nutrients may have a
      role in human prostatic carcinogenesis, since the anterior and dorsal lobes of
      the mouse prostate are homologous with the human prostate in embryological origin
      and histological structure and carcinomas induced in rodent models have similar
      characteristics to those found in human prostatic cancer.

PMID- 9163687
TI  - Chemopreventive efficacies of aspirin and sulindac against lung tumorigenesis in
      A/J mice.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely
      prescribed drugs. In this study, we demonstrated the efficacy of aspirin to
      inhibit lung tumorigenesis in A/J mice. Lung tumors (9.9 tumors/mouse) were
      induced by the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)
      1-butanone (NNK), administered in drinking water between week 0 and week +7.
      Groups of mice were fed sulindac (123 mg/kg diet), acetylsalicylic acid (ASA; 294
      mg/kg), non-buffered Aspirin (294 mg/kg) or buffered Aspirin (294 mg/kg) in AIN
      76A diet from week -2 to the end of the bioassay (week +23). These doses are
      comparable to the maximal doses recommended for humans. ASA and non-buffered
      Aspirin were the most effective inhibitors and reduced lung multiplicities by 60
      and 62%, respectively. Sulindac inhibited lung tumor multiplicity by 52%.
      Inhibition by buffered Aspirin was not statistically significant. We evaluated
      the efficacies of NSAIDs to inhibit NNK activation by h1A2 v2 cells expressing
      human P-450 1A2. Salicylates, at doses of 500 microM and 1 mM, had no effect on
      NNK activation. Sulindac and its sulfide and sulfone metabolites (1 mM) inhibited
      NNK metabolism by 90, 92 and 65%, respectively. We observed a 76% inhibition with
      SKF 525A, a P-450 inhibitor. Taken together, these results indicate that
      salicylates and sulindac could be equally effective as chemopreventive agents,
      but they could differ in their mode of action.

PMID- 9163688
TI  - Effect of caloric restriction on pre-malignant and malignant stages of mammary
      carcinogenesis.
AB  - Caloric restriction has documented beneficial effects on numerous diseases
      including cancer, yet the mechanism(s) that accounts for these wide ranging
      benefits is unknown. Part of the difficulty in defining mechanisms has been the
      long-term nature of experimental protocols in which these beneficial effects have
      been observed and the inherent difficulty of investigating mechanisms in such
      studies. The experiments reported were designed: (1) to determine if caloric
      restriction would inhibit mammary carcinogenesis in a model for this disease
      process that is 35 days in duration; (2) to determine if progression from pre
      malignant to malignant stages of mammary carcinogenesis was affected by caloric
      restriction; and (3) to explore whether the effects of caloric restriction were
      associated with changes in adrenal function. Mammary carcinogenesis was induced
      in female Sprague-Dawley rats by the i.p. administration of 1-methyl-1
      nitrosourea (50 mg/kg body weight) at 21 days of age. Rats were randomized to one
      of four dietary treatment groups: ad libitum fed, or restriction of food intake
      to 90, 80 or 60% of the ad libitum intake. Rats were palpated for detection of
      mammary tumors and all mammary lesions excised at necropsy were histologically
      classified. Twenty-four-hour collections of urine were obtained at weekly
      intervals throughout the 35-day experiment. Urine was assayed for corticosterone
      by direct radioimmunoassay. Caloric restriction resulted in both a dose dependent
      prolongation of latency to palpable carcinomas (P < 0.01) and a reduction in
      final incidence of mammary cancer; the dose response was linear (P < 0.05). The
      percentage of pre-malignant mammary lesions in a group increased with increasing
      degree of caloric restriction, whereas the percentage of carcinomas decreased (P
      < 0.05). The level of cortical steroid increased linearly with increasing caloric
      restriction (P < 0.01) an effect that was not attenuated over time. Poisson
      regression analyses with the number of cancers per rat as the dependent variable,
      level of caloric restriction as the independent variable and urinary cortical
      steroid excretion as a co-variate were performed. These analyses indicated that
      the variation in cancers per rat, irrespective of the treatment group to which an
      animal was assigned, could be accounted for by urinary cortical steroid excretion
      (P<0.05); i.e. urinary cortical steroid excretion was an independent predictor of
      an animal's carcinogenic response. The data reported in this study support the
      use of a short term model to study the mechanism(s) by which caloric restriction
      inhibits mammary carcinogenesis and point to both a stage in the disease process,
      the conversion of pre-malignant to malignant cells, and a target tissue (adrenal
      gland) and chemical species (adrenal cortical steroid) that may be involved in
      mediating the protective effects of energy restriction. These data indicate the
      feasibility of identifying a chemical basis for the protective effect of caloric
      restriction that is independent of energy restriction per se and this, in turn,
      indicates that it may be possible to circumvent the practical problem of
      implementing a program of chronic energy restriction in human populations, yet
      still achieve the wide-ranging health benefits of such a program.

PMID- 9163689
TI  - Carcinogenesis induced by UVA (365-nm) radiation: the dose-time dependence of
      tumor formation in hairless mice.
AB  - Although ultraviolet B (UVB wavelengths 280-315 nm) dominates the carcinogenic
      effect of sunlight, ultraviolet A (UVA 315-400 nm) is estimated to contribute 10
      20% to the carcinogenic dose; a substantial background that is not affected by a
      depletion of the ozone layer. Furthermore, certain high-power modern tanning
      lamps emit mainly long wave UVA (UVA1; 340-400 nm). For a proper risk estimate of
      UVA exposure its carcinogenicity relative to that of UVB exposure needs to be
      determined more accurately. To this end we determined the dose-time relationship
      for skin tumor induction in hairless mice that were irradiated daily with custom
      made Philips 365-nm sources. Irradiation of the group exposed to the highest of
      the four daily doses (430, 240, 140 and 75 kJ/m2) had to be discontinued because
      severe scratching set in after 3 months (no tumors). In the lower dose-groups the
      prevalence curves for skin carcinomas (percentage of tumor-bearing mice versus
      logarithm of time) ran virtually parallel, and were similar to those found with
      daily UVB exposure. However, the relationship between the daily dose (D) and the
      median tumor induction time (t50) appeared to differ: with UVB we found that t50
      D(r) = constant, with r = 0.6, whereas with UVA1 we found r approximately 0.4.
      This would imply that 365-nm carcinogenesis shows less of a dose-dependency than
      UVB carcinogenesis, and that 365-nm radiation becomes more carcinogenic, relative
      to UVB, as the daily doses are lowered. This relative shift at low doses
      complicates extrapolation of UVB to UVA risks in humans. Based on the t50 from
      the lowest dose-group we found that the carcinogenicity at 365 nm (per J/m2) is
      0.9 x 10(-4) times that at 293 nm, the wavelength of maximum carcinogenicity in
      hairless mice. This result for 365-nm carcinogenicity falls well within the
      margins of error of the wavelength dependency that was estimated earlier from
      experiments with broadband UV sources.

PMID- 9163690
TI  - Induction and repair inhibition of oxidative DNA damage by nickel(II) and
      cadmium(II) in mammalian cells.
AB  - Compounds of nickel(II) and cadmium(II) are carcinogenic to humans and to
      experimental animals. One frequently discussed mechanism involved in tumor
      formation is an increase in reactive oxygen species by both metals with the
      subsequent generation of oxidative DNA damage. In the present study we used human
      HeLa cells to investigate the potential of nickel(II) and cadmium(II) to induce
      DNA lesions typical for oxygen free radicals in intact cells and the effect on
      their repair. As indicators of oxidative DNA damage, we determined the
      frequencies of DNA strand breaks and of lesions recognized by the bacterial
      formamidopyrimidine-DNA glycosylase (Fpg protein), including 7,8-dihydro-8
      oxoguanine (8-hydroxyguanine), a pre-mutagenic DNA base modification. Nickel(II)
      caused a slight increase in DNA strand breaks at 250 microM and higher, while the
      frequency of Fpg-sensitive sites was enhanced only at the cytotoxic concentration
      of 750 microM. The repair of oxidative DNA lesions induced by visible light was
      reduced at 50 microM and at 100 microM nickel(II) for Fpg-sensitive sites and DNA
      strand breaks, respectively; the removal of both types of lesions was blocked
      nearly completely at 250 microM nickel(II). In the case of cadmium(II), DNA
      strand breaks occurred at 10 microM and no Fpg-sensitive sites were detected.
      However, the repair of Fpg-sensitive DNA lesions induced by visible light was
      reduced at 0.5 microM cadmium(II) and higher, while the closure of DNA strand
      breaks was not affected. Since oxidative DNA damage is continuously induced
      during aerobic metabolism, an impaired repair of these lesions might well explain
      the carcinogenic action of nickel(II) and cadmium(II).

PMID- 9163691
TI  - p53 protein expression by hepatocarcinogens in the rat liver and its potential
      role in mitoinhibition of normal hepatocytes as a mechanism of hepatic tumour
      promotion.
AB  - The tumour suppressor gene p53 is expressed in response to DNA-damage; its
      protein product blocks cells in the G1-phase of the cell cycle. This gives cells
      additional time to repair their DNA-damage. However, it may trigger apoptosis if
      damage is too high. Loss of p53 function appears to be an important step in
      carcinogenesis because 50% of human tumours have lost functional p53. In order to
      study the role of p53 in experimental hepatocarcinogenesis, we determined the
      expression of p53 in rat liver in response to various hepatocarcinogenic and
      hepatotoxic compounds. Administration of hepatocarcinogenic compounds increased
      p53 protein levels in the liver as detected by immunoprecipitation followed by
      SDS-PAGE and Western blotting with ECL-detection. The hepatocarcinogens included
      N-hydroxy-2-acetylaminofluorene, aflatoxin B1, and diethylnitrosamine. Their
      structural analogues N-hydroxy-4-acetylaminobiphenyl and ethyl methane-sulphonate
      which are not hepatocarcinogenic, did not induce p53. Also, two hepatotoxic
      compounds (carbon tetrachloride, D-galactosamine) did not induce p53. Other
      compounds that induced p53 in the rat liver were 2-aminofluorene (administered by
      drinking water for two weeks) and tris-(2,3-dibromopropyl)phosphate.
      Benzo[a]pyrene did not induce p53. N-Hydroxy-2-acetylaminofluorene, aflatoxin B1,
      and diethylnitrosamine are potent hepatic tumour promoters. At the same time,
      they induce p53 protein expression and inhibit proliferation of normal
      hepatocytes. Because this is not observed with non-hepatocarcinogenic analogues,
      it suggests an involvement of p53 expression in hepatic tumour promotion. A
      possible mechanism is discussed.

PMID- 9163692
TI  - Fpg protein releases a ring-opened N-7 guanine adduct from DNA that has been
      modified by sulfur mustard.
AB  - Transfection of the Escherichia coli fpg gene into Chinese hamster ovary cells
      has been reported to enhance survival after exposure to aziridine (C. Cussac and
      F.Laval, 1996, Nucleic Acids Res., 24, 1742-1746). This result suggests that Fpg
      protein protects cells from toxicity by removing ring-opened N-7 guanine adducts
      from DNA, and raises the possibility that Fpg protein would offer protection from
      other agents that alkylate the N-7 position of guanine. Since the major adduct
      formed by sulfur mustard in DNA is 7-hydroxyethyl-thioethylguanine (HETEG), we
      have investigated the action of Fpg protein on the ring-opened form of this
      adduct (ro-HETEG). A substrate containing ro-HETEG was prepared by alkaline
      treatment of DNA modified by [14C]sulfur mustard. Fpg protein purified from an
      over-producing strain of E. coli released ro-HETEG from this substrate in an
      enzyme- and time-dependent manner, and at a rate that is similar to that at which
      it releases ring-opened 7-methylguanine. Thus, Fpg protein acts efficiently on ro
      HETEG, and may offer some protection against the toxic action of sulfur mustard.

PMID- 9163693
TI  - Urinary excretion of 3-methyladenine after consumption of fish containing high
      levels of dimethylamine.
AB  - The urinary excretion of the DNA alkylation product, 3-methyladenine (3-MeAde),
      was measured in human volunteers who were on controlled diets and consumed fresh
      fish, or frozen-stored fish that contained 50-fold higher levels of dimethylamine
      (DMA), with or without ingested nitrate. DMA potentially could react with
      nitrosating agents in the diet or within the body, and produce the potent
      carcinogen N-nitrosodimethylamine (NDMA), which can then react with DNA to form
      several adducts including 3-MeAde. Our findings show that there was no increase
      in urinary levels of 3-MeAde after consumption of fish preserved by frozen
      storage relative to levels after consumption of fresh fish. Furthermore,
      consumption of 225 mg sodium nitrate (equal to the nitrate content in a large
      glass of beet juice) at 1 h prior to consumption of the frozen-stored fish did
      not increase urinary 3-MeAde levels as would be expected if nitrate enhanced
      endogenous nitrosation of DMA. In contrast, urinary excretion of 3-MeAde from a
      volunteer who was a moderate cigarette smoker (11 cigarettes per day) was
      approximately 3- to 8-fold higher than dietary 3-MeAde intake. These findings
      indicate that consumption of high levels of DMA in fish does not result in
      detectable levels of NDMA formation and genetic damage as measured by the urinary
      biomarker 3-MeAde.

PMID- 9163694
TI  - Relative mutagenicities of gaseous nitrogen oxides in the supF gene of pSP189.
AB  - Gaseous nitric oxide (NO), an environmental pollutant found in cigarette smoke
      and diesel exhaust, has been shown to generate mutations in aerobic in vitro
      assays. The objective of this study was to identify which oxides of nitrogen,
      formed in the gaseous phase from NO, possess mutagenic activity. Samples of the
      plasmid pSP189, in 1 M HEPES buffer, pH 7.4, were exposed to preparations of
      nitrogen dioxide (NO2), dinitrogen trioxide (N2O3) or an air control. The gas
      mixtures were formed in a gas-tight syringe and were then introduced into 1 l
      flasks. The plasmid solution was introduced immediately afterwards.
      Transformation of Escherichia coli strain MBM7070 with the treated plasmids
      allowed analysis of mutation frequencies and the types of mutations induced in
      the target supF gene. The mutation frequency resulting from NO2 exposure was not
      different from that of the control. However, N2O3 produced a substantial number
      of mutations. The mutation frequency and the types of mutations were found to
      depend on the length of time that the gases were allowed to incubate in the
      syringe prior to introduction into the 1 l flasks (mutation frequency was maximal
      at approximately 2 min). The most prevalent mutations were AT-->GC transitions
      (68%), followed by GC-->AT transitions (30%), similar to previous findings when
      pure NO was bubbled through pSP189 solutions. These results suggest that it is
      N2O3, rather than NO2, that is the most likely source of mutagenic potential from
      gaseous nitrogen oxides.

PMID- 9163695
TI  - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine increases the numbers of tumors,
      cystic crypts and aberrant crypt foci in multiple intestinal neoplasia mice.
AB  - The multiple intestinal neoplasia (Min) mice have a mutation in the murine
      adenomatous polyposis coli (Apc) gene rendering them highly susceptible to
      spontaneous intestinal adenoma formation, similar to the familial adenomatous
      polyposis (FAP) syndrome in humans. We studied whether the most abundant
      mutagenic heterocyclic amine isolated from cooked food, 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP), could influence early intestinal neoplasia
      in C57BL/6J-Min/+ and C57BL/6J- +/+ (wild-type) mice of both sexes. PhIP was
      given in 4 weekly i.p. injections of 50 mg/kg. Ten weeks after the start of the
      experiment, PhIP had significantly increased the numbers of small tumors and
      cystic crypts in the proximal section of the small intestine in male Min/+ mice,
      and the numbers of aberrant crypt foci (ACF) in the large intestines of both
      males and females. The effects of PhIP were more pronounced in male than in
      female Min/+ mice. In +/+ mice, no tumors or cystic crypts in the small
      intestine, and no tumors and only a very few ACF in the large intestine, were
      induced by PhIP. These results show that a substance frequently present in the
      human diet is able to enhance the neoplastic process induced by a genetic lesion,
      which is also commonly found both in inherited and sporadic colon carcinomas in
      humans.

PMID- 9163696
TI  - Comparison of DNA adduct formation by aristolochic acids in various in vitro
      activation systems by 32P-post-labelling: evidence for reductive activation by
      peroxidases.
AB  - Aristolochic acid I (AAI) and aristolochic acid II (AAII), the two major
      components of the carcinogenic plant extract aristolochic acid (AA), are known to
      be mutagenic and to form DNA adducts in vivo. According to the structures of the
      major DNA adducts identified in animals and humans, nitroreduction is the crucial
      pathway in the metabolic activation of these naturally occurring nitroarenes to
      their ultimate carcinogenic species. Using the nuclease P1-enhanced version of
      the 32P-post-labelling assay we investigated the formation of DNA adducts by AAI
      and AAII in different in vitro activation systems in order to determine the most
      suitable in vitro system mimicking target tissue activation. Although DNA adducts
      resulting from oxidative activation of AAs have not yet been identified both
      reductive and oxidative in vitro systems were employed. In vitro incubations were
      conducted under standardized conditions (0.3 mM AAs; 4 mM dNp as calf thymus DNA)
      using rat liver microsomes, xanthine oxidase (a mammalian nitroreductase),
      horseradish peroxidase, lactoperoxidase and chemical reduction by zinc. Enzymatic
      incubations were performed under aerobic and anaerobic conditions. A combination
      of two independent chromatographic systems (ion-exchange chromatography and
      reversed-phase HPLC) with reference compounds was used for the identification of
      DNA adducts detected by the 32P-post-labelling assay. The two known major adducts
      of AAI or AAII found in vivo were generated by all in vitro systems except for
      incubations with AAII and horseradish peroxidase where two unknown adducts
      predominated. Irrespective of the in vitro activation system used, the majority
      of adduct spots obtained were identified as the previously characterized four AA
      DNA adducts: dA-AAI, dA-AAII, dG-AAI and dG-AAII. This indicates that both
      reductive and peroxidative activation of AAI or AAII resulted in
      chromatographically indistinguishable DNA adducts. Thus, peroxidase mediated
      activation of AAs led to the formation of the same adducts that had been observed
      in vivo and upon reductive activation in several in vitro systems. Quantitative
      analyses of individual adducts formed in the various in vitro systems revealed
      relative adduct labelling (RAL) values over a 100,000-fold range from 4 in 10(3)
      for activation of AAII to deoxyadenosine adducts by zinc to only 3 in 10(8) for
      activation of AAII by lactoperoxidase. The extent of DNA modification by AAI was
      higher than by AAII in all enzymatic in vitro systems. Only activation by zinc
      resulted in higher total binding to exogenous DNA by AAII than by AAI. Aerobic
      incubations with rat liver microsomes generated AAI- and AAII-DNA adduct profiles
      reproducing profiles in target tissue (forestomach) of rats, thus providing the
      most appropriate activation among the in vitro systems tested.

PMID- 9163697
TI  - 32P-post-labelling analysis of DNA adducts formed by aristolochic acid in tissues
      from patients with Chinese herbs nephropathy.
AB  - Recently, we reported that aristolochic acid (AA) a naturally occurring
      nephrotoxin and carcinogen is implicated in a unique type of renal fibrosis,
      designated Chinese herbs nephropathy (CHN). Indeed, we identified the principal
      aristolochic acid-DNA adduct in the kidney of five such patients. We now extend
      these observations and demonstrate the presence of additional AA-DNA adducts by
      the 32P-post-labelling method not only in the kidneys, but also in a ureter
      obtained after renal transplantation. Using the nuclease P1 version of the assay
      not only the major DNA adduct of aristolochic acid, 7-(deoxyadenosin-N6-yl)
      aristolactam I (dA-AAI), but also the minor adducts, 7-(deoxyguanosin-N2-yl)
      aristolactam I (dG-AAI) and 7-(deoxyadenosin-N6-yl)-aristolactam II (dA-AAII)
      were detected, and identified by cochromatographic analyses with TLC and HPLC.
      Quantitative analyses of six kidneys revealed relative adduct levels from 0.7 to
      5.3/10(7) for dA-AAI, from 0.02 to 0.12/10(7) for dG-AAI and 0.06 to 0.24/ 10(7)
      nucleotides for dA-AAII. The detection of the dA-AAII adduct is consistent with
      the occurrence of aristolochic acid II (AAII) in the herb powder imported under
      the name of Stephania tetrandra and confirms that the patients had indeed
      ingested the natural mixture of AAI and AAII. 32P-post-labelling analyses of
      further biopsy samples of one patient showed the known adduct pattern of AA
      exposure not only in the kidney, but also in the ureter, whereas in skin and
      muscle tissue no adduct spots were detectable. In an attempt to explain the
      higher level of the dA-AAI adduct compared to the dG-AAI adduct level in renal
      tissue even 44 months after the end of regimen, the persistence of these two
      purine adducts was investigated in the kidney of rats given a single oral dose of
      pure AAI. In contrast to the dG-AAI adduct, the dA-AAI adduct exhibited a
      lifelong persistence in the kidney of rats. Our data demonstrate that AA forms
      DNA adducts in human tissue by the same activation mechanism(s) reported from
      animal studies. Thus, the carcinogenic/mutagenic activity of AA observed in
      animals could also be responsible for the urothelial cancers observed in two of
      the CHN patients.

PMID- 9163699
TI  - Loss of tumor-promoting activity of unleaded gasoline in N-nitrosodiethylamine
      initiated ovariectomized B6C3F1 mouse liver.
AB  - Unleaded gasoline (UG) vapor (2056 ppm) increased the incidence of liver tumors
      in a chronic bioassay and exhibited tumor-promoting activity in N
      nitrosodiethylamine (DEN)-initiated female mouse liver. Estrogen inhibited mouse
      liver tumor development and the hepatocarcinogenic and tumor-promoting dose of UG
      produced uterine changes suggestive of estrogen antagonism. To directly test the
      hypothesis that UG-induced tumor-promoting ability is secondary to its
      interaction with the mouse liver tumor inhibitor, estrogen, we compared the tumor
      promoting ability of UG in ovariectomized (Ovex) mice with the hepatic tumor
      promoting ability of UG in intact mice. Ovaries were surgically removed at 4
      weeks of age. Exposure to wholly vaporized UG (2018 ppm) under bioassay and tumor
      promoting conditions began at 8 weeks of age. After 4 months of exposure, UG
      increased relative liver weight and hepatic microsomal cytochrome P450
      pentoxyresourfin-O-dealkylase and ethoxyresorufin-O-deethylase activity to a
      similar extent in intact and Ovex mice. Non-focal hepatocyte proliferation, as
      measured by the incorporation of bromo-deoxyuridine, was not changed by UG
      exposure and was similar in all treatment groups. After 4 months of exposure to
      DEN-initiated mice, UG significantly increased the volume fraction of liver
      occupied by foci (three-fold) as compared to control intact mice. As expected,
      volume of foci was elevated in DEN/Ovex/control mice as compared to
      DEN/intact/control mice. In DEN/Ovex mice UG did not significantly increase the
      focal volume fraction. Thus, the tumor promoting activity of UG, as demonstrated
      by increased volume fraction of liver occupied by hepatic foci in intact mice, is
      greatly attenuated in Ovex mice. The volume fraction data in Ovex mice support
      the hypothesis that the tumor promoting activity of UG is dependent upon the
      interaction of UG with ovarian hormones. These data also indicate that hepatic
      microsomal cytochrome P450 PROD and EROD induction, hepatomegaly and non-focal
      hepatic LI are not specific markers of hepatic tumor promoting activity of UG.

PMID- 9163698
TI  - Microsatellite instability and loss of heterozygosity in chromosomes 9 and 16 in
      human breast epithelial cells transformed by chemical carcinogens.
AB  - Microsatellite instability (MSI) and loss of heterozygosity (LOH) in chromosomes
      9 and 16 have been reported in human breast cancers. In order to determine
      whether changes in these chromosomes play a role in the initiation and
      progression of this disease, we performed microsatellite polymorphism analyses in
      human breast epithelial cells (HBEC) transformed by chemical carcinogens, an in
      vitro system that recapitulates various stages of neoplastic transformation. In
      this experimental system we studied the mortal HBEC MCF-10M, immortal MCF-10F
      cells, derived from MCF-10M cells, and clones derived from MCF-10F cells treated
      with benzo[a]pyrene (B[a]P) (BP1 and BP1E) and 7,12-dimethylbenz[a]anthracene
      (DMBA) (D3 and D3-1). The four clones of transformed cells were injected into
      severe combined immunodeficient (SCID) mice. Only BP1-E cells induced the
      formation of tumors, designated BP1E-Tp cells. These cells originated six
      additional tumors, designated BP1E-Tf no. 1 through Tf no. 6. Microsatellite
      analyses were carried out using five markers for chromosome 9 and 20 for
      chromosome 16. There was no evidence of MSI or LOH in clones BP1 and BP1E when
      compared with the MCF-10M and MCF-10F cells, whereas BP1E-Tp cells and Bp1E-Tf
      no. 1-Tf no. 6 tumors exhibited MSI at loci p23 and p21, and LOH at p21-22 of
      chromosome 9. They also exhibited MSI and LOH at multiple loci of both the short
      and long arms of chromosome 16, i.e. p13.13, p13.3, p12, q12.1, q12.2, q23 and
      q24, to which putative tumor suppressor genes have been localized. Clones D3 and
      D3-1 exhibited no genomic changes in chromosome 9, but did show MSI at locus
      q12.1 of chromosome 16 using marker D16S285. Although the cells treated with DMBA
      expressed early phenotypes of neoplastic transformation, they were not
      tumorigenic, and also manifested fewer changes than the tumorigenic BP1E-Tp cells
      and the tumors BP1E-Tf. The changes in chromosomes 9 and 16 observed in these
      latter ones indicated an association with the expression of tumorigenesis, which
      represents a late event in the progression of the neoplastic transformation of
      HBEC. Of interest was the observation that HBEC transformed by chemical
      carcinogens in vitro express genomic changes similar to those found in
      spontaneous breast carcinomas.

PMID- 9163700
TI  - Metabolic activation of aromatic amines by human pancreas.
AB  - Epidemiologic studies have suggested that aromatic amines (and nitroaromatic
      hydrocarbons) may be carcinogenic for human pancreas. Pancreatic tissues from 29
      organ donors (13 smokers, 16 non-smokers) were examined for their ability to
      metabolize aromatic amines and other carcinogens. Microsomes showed no activity
      for cytochrome P450 (P450) 1A2-dependent N-oxidation of 4-aminobiphenyl (ABP) or
      for the following activities (and associated P450s): aminopyrine N-demethylation
      and ethylmorphine N-demethylation (P450 3A4); ethoxyresorufin O-deethylation
      (P450 1A1) and pentoxyresorufin O-dealkylation (P450 2B6); p-nitrophenol
      hydroxylation and N-nitrosodimethyl-amine N-demethylation (P450 2E1); lauric acid
      omega-hydroxylation (P450 4A1); and 4-(methylnitrosamino)-1-(3-pyridyl-1-butanol)
      (NNAL) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) alpha-oxidation
      (P450 1A2, 2A6, 2D6). Antibodies were used to examine microsomal levels of P450
      1A2, 2A6, 2C8/9/18/19, 2E1, 2D6, and 3A3/4/5/7 and epoxide hydrolase. Immunoblots
      detected only epoxide hydrolase at low levels; P450 levels were <1% of liver.
      Microsomal benzidine/prostaglandin hydroperoxidation activity was low. In
      pancreatic cytosols and microsomes, 4-nitrobiphenyl reductase activities were
      present at levels comparable to human liver. The O-acetyltransferase activity
      (AcCoA-dependent DNA-binding of [3H]N-hydroxy-ABP) of pancreatic cytosols was
      high, about twothirds the levels measured in human colon. Cytosols showed high
      activity for N-acetylation of p-aminobenzoic acid, but not of sulfamethazine,
      indicating that acetyltransferase-1 (NAT1) is predominantly expressed in this
      tissue. Cytosolic sulfotransferase was detected at low levels. Using 32P-post
      labeling enhanced by butanol extraction, putative arylamine-DNA adducts were
      detected in most samples. Moreover, in eight of 29 DNA samples, a major adduct
      was observed that was chromatographically identical to the predominant ABP-DNA
      adduct, N-(deoxyguanosin-8-yl)-ABP. These results are consistent with a
      hypothesis that aromatic amines and nitroaromatic hydrocarbons may be involved in
      the etiology of human pancreatic cancer.

PMID- 9163701
TI  - Bioreductive activation of catechol estrogen-ortho-quinones: aromatization of the
      B ring in 4-hydroxyequilenin markedly alters quinoid formation and reactivity.
AB  - There is a clear association between excessive exposure to estrogens and the
      development of cancer in several tissues including breast and endometrium. The
      risk factors for women developing these cancers are all associated with longer
      estrogen exposure, as may be facilitated by early menses, late menopause and long
      term estrogen replacement therapy. Equilenin (1,3,5(10),6,8-estrapentaen-3-ol-17
      one) or its 17-hydroxylated analogs make up 15% of the most widely prescribed
      estrogen replacement formulation, Premarin, and yet there is very little
      information on the human metabolism of these estrogens. In this study, we
      synthesized the catechol metabolite of equilenin, 4-hydroxyequilenin, and
      examined how aromatization of the B ring affects the formation and reactivity of
      the o-quinone (3,5-cyclohexadien-1,2-dione). 4-Hydroxyequilenin-o-quinone is much
      more redox-active and longer-lived than the endogenous catechol estrone-o
      quinones, which suggests that the mechanism(s) of toxicity of the former could be
      quite different. Interestingly, the rate of reduction of the 4-hydroxyequilenin-o
      quinone is increased at least 13-fold in the presence of NAD(P)H:quinone
      oxidoreductase (DT-diaphorase). Once NADH is consumed however, the catechol auto
      oxidized rapidly to the o-quinone. NADH consumption was accompanied by dicumarol
      sensitive oxygen uptake both with the purified enzyme and with cytosol from human
      melanoma cells with high levels of DT-diaphorase activity. P450 reductase and rat
      liver microsomes also catalyzed NADPH consumption and oxygen uptake. 4
      Hydroxyestrone-o-quinone was also rapidly reduced by NAD(P)H; however, this o
      quinone does not auto-oxidize and once the o-quinone is reduced the reaction
      terminates. Including oxidative enzymes in the incubation completes the redox
      couple and 4-hydroxyestrone-o-quinone behaves like 4-hydroxyequilenin-o-quinone.
      These data suggest that reduction of estrogen-o-quinones may not result in
      detoxification. Instead this could represent a cytotoxic mechanism involving
      consumption of reducing equivalents (NADH/NADPH) as well as formation of
      superoxide and other reactive oxygen species leading to oxidative stress.
      Finally, we have compared the cytotoxicity of 4-hydroxyequilenin with that of the
      estrone catechols in human melanoma cells. 4-Hydroxyequilenin is 5-fold more
      toxic in these cells compared with 4-hydroxyestrone (ED50 = 7.8 versus 38 microM,
      respectively) suggesting that formation of the longer-lived redox-active 4
      hydroxyequilenin-o-quinone was responsible for the cytotoxic differences. These
      results substantiate the conclusion that the involvement of quinoids in catechol
      estrogen toxicity depends on a combination of the rate of formation of the o
      quinone, the lifetime of the o-quinone, and the electrophilic/redox reactivity of
      the quinoids.

PMID- 9163702
TI  - Suppression by phenobarbital of ethionine-induced hepatocellular carcinoma
      formation and hepatic S-adenosylethionine levels.
AB  - An 18-month carcinogenicity study was conducted in male weanling F344 rats
      (28/group) to examine the effects of the simultaneous feeding of selected
      concentrations of ethionine and 0.05% phenobarbital in a normal chow diet. The
      effects of a 1-6-week feeding of phenobarbital and ethionine on the hepatic
      levels of the related metabolites S-adenosylmethionine, S-adenosylhomocysteine
      and S-adenosylethionine were also examined. Ethionine at 0.3% or 0.1% induced
      hepatocellular carcinoma (HCCa) at incidences of 90% (19/21) and 89% (24/27),
      respectively. Adding phenobarbital to the 0.1% ethionine diet reduced the
      incidence of HCCa to 36% (10/28) and reduced the number of liver tumor-associated
      deaths occurring prior to terminal sacrifice from 10/27 to 1/28. No hepatic
      tumors were observed in rats fed 0, 0.003, 0.01, or 0.03% ethionine.
      Phenobarbital alone or combined with 0.03% ethionine produced no hepatic tumors.
      Dietary ethionine at 0.1% reduced the intracellular hepatic level of S
      adenosylmethionine to <50% of that seen in control rats. Phenobarbital alone had
      little effect on either S-adenosylmethionine or S-adenosylhomocysteine levels.
      The combination of phenobarbital and 0.1% ethionine led to increases in the
      hepatic levels of S-adenosylmethionine of 40-60% after 3 and 6 weeks of feeding,
      compared to those seen in rats receiving 0.1% ethionine alone. Ethionine feeding
      resulted in high levels of S-adenosylethionine in the livers. Combining
      phenobarbital with ethionine in the diet led to 30-50% reductions in hepatic S
      adenosylethionine content. The results indicate that phenobarbital inhibits
      hepatocarcinogenesis by ethionine, that ethionine may cause HCCa via methyl group
      insufficiency, and that at levels of < or =0.03% ethionine did not show evidence
      of tumorigenicity.

PMID- 9163703
TI  - Depletion of hepatocyte nuclear estrogen receptor expression is associated with
      promotion of tamoxifen induced GST-P foci to tumours in rat liver.
AB  - The expression of hepatocyte nuclear estrogen receptor (ER) in putative
      preneoplastic foci, adenomas and carcinomas, induced by the rat liver carcinogen
      tamoxifen, has been examined immunohistologically. ER staining of normal rat
      liver shows between 30-50% of hepatocyte nuclei to be positive, depending on
      fixation. Depletion of ER was defined as <10% of cells in foci or tumours
      staining for nuclear ER. A proportion of all but the smallest glutathione-S
      transferase, placental form (GST-P) expressing foci had depleted expression of
      nuclear ER. The percentage of GST-P expressing foci with depletion of nuclear ER
      increased with the size of the foci. The liver adenomas and carcinomas induced by
      tamoxifen showed a high incidence (90%) of depletion of ER. This suggests that
      abnormal expression of the ER is associated with the promotion of putative
      preneoplastic foci to adenomas and carcinomas in tamoxifen exposed rat livers.
      Dysfunction of the ER could contribute to selective continued stimulation of
      initiated cells that would be consistent with a role for modification of the ER
      in target cells and the promotion stage of liver cancer. Liver tumours induced by
      other carcinogens in both sexes of rat were also found to have a high incidence
      of ER depletion, indicating that this could be a general regulatory mechanism for
      rat liver tumour promotion, irrespective of the possible estrogen like action of
      individual carcinogens.

PMID- 9163705
TI  - Infrequent mutations of the transforming growth factor beta-type II receptor gene
      at chromosome 3p22 in human lung cancers with chromosome 3p deletions.
AB  - Mutations in the transforming growth factor beta-type II receptor (TGFbeta RII)
      gene have been detected in several types of human cancers that represent the
      phenotype of genomic instability. The TGFbeta RII gene has been mapped to
      chromosome 3p, on which loss of heterozygosity (LOH) was frequently detected in
      both small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC).
      To investigate whether the TGFbeta RII gene on 3p22 is inactivated in lung
      cancers, we examined 35 sporadic lung cancers (15 SCLC and 20 NSCLC) with LOH on
      3p for mutations of the TGFbeta RII gene. We previously produced eight intron
      based primer pairs for mutational analysis of the entire coding region of the
      TGFbeta RII gene. Using these primers, we screened for mutations of the TGFbeta
      RII gene by polymerase chain reaction-single strand conformational polymorphism
      (PCR-SSCP) analysis. A mutation was detected in a case of SCLC: one base
      insertion in the polyadenine tract of exon 3. This tumor showed the replication
      error (RER) phenotype. There were no mutations in exons 1, 2, 4, 5, 6 and 7.
      These results indicate that the polyadenine tract is a mutational hot spot in the
      TGFbeta RII gene in RER positive tumors, and that TGFbeta RII mutations occur
      rarely in lung cancers with LOH on chromosome 3p.

PMID- 9163704
TI  - A xanthine oxidase inhibitor 1'-acetoxychavicol acetate inhibits azoxymethane
      induced colonic aberrant crypt foci in rats.
AB  - The modifying effect of dietary administration of a xanthine oxidase inhibitor 1'
      acetoxychavicol acetate (ACA) present in an edible plant Languas galanga in
      Thailand on the development of azoxymethane (AOM)-induced colonic aberrant crypt
      foci (ACF) was investigated in rats. Male F344 rats were given s.c. injections of
      AOM (15 mg/kg body wt) once a week for 3 weeks to induce colonic ACF. They were
      fed the diets containing 100 or 200 ppm ACA for 5 weeks, starting 1 week before
      the first dosing of AOM. At the termination of the study (week 5), AOM induced
      118 +/- 28 ACF/colon. Dietary administration of ACA caused significant reduction
      in the frequency of ACF (41% inhibition by 100 ppm ACA feeding and 37% inhibition
      by 200 ppm ACA feeding, P<0.01). Such inhibition might be associated with
      suppression of the proliferation biomarkers' expression such as ornithine
      decarboxylase activity in the colonic mucosa, number of silver-stained nucleolar
      organizer regions' protein in the colonic mucosal cell nuclei and blood polyamine
      content. These results indicate that ACA could inhibit the development of AOM
      induced ACF through its suppression of cell proliferation in the colonic mucosa
      and ACA might be a possible chemopreventive agent against colon tumourigenesis.

PMID- 9163706
TI  - Spectrum of clinical and laboratory characteristics of HIV infection in northern
      India.
AB  - To define the impact of HIV infection in India, the clinical and laboratory
      profile and the correlation of CD4 count to the likely opportunistic infection in
      a cohort of 134 HIV positive patients in Northern India was analysed. Majority of
      the patients, 72% and 67.8% (children and adults respectively) were asymptomatic,
      having been detected during routine screening and maintained that status for a
      median follow-up period of 3 years. Among the symptomatic patients, oropharyngeal
      candidiasis was the most common opportunistic infection followed closely by
      tuberculosis (both pulmonary and extra pulmonary) around 3.6-4.0 years from
      probable HIV infection with a median CD4 of 420-578 per cmm. Infection with
      Cryptococcosis, Cryptosporidiosis and cytomegalovirus occurred only after a
      significant fall in CD4 to < 100/cmm usually around 8-10 years from probable HIV
      infection. Pneumocystis carinii pneumonia was the terminal event among the 12
      deaths at a mean CD4 count of 6/cmm. Non specific constitutional symptoms like
      fever, prolonged diarrhoea and significant weight loss were frequent. In general,
      the clinical profile of Indian patients with HIV bears much resemblance to
      African countries owing perhaps to the similar background of poverty,
      malnutrition and endemic infection.

PMID- 9163707
TI  - Heterophyid eggs in human stool samples in Assam: first report for India.
AB  - Two cases from a Muslim family in upper Assam were found to pass trematode eggs
      morphologically similar to the members of the family Heterophyidae Odhner, 1914.
      The eggs characteristically yellowish brown in colour, ovoid, have a thick shell
      and are operculate. They measured 31.5 +/- 2.0 um SD x 22.4 +/- 1.9 um SD with
      well developed miracidium. This is the first record of human heterophyid
      infection from India.

PMID- 9163708
TI  - Insecticidal activity of some new synthetic compounds against different mosquito
      species.
AB  - Insecticidal activity of an organosilane (HOE 84498, OMS 3055), Organophosphorous
      (MAT 9460, OMS 3052) and a synthetic pyrethroid compound (Trebon, OMS 3002) was
      evaluated against adult and larval stages of eight species of mosquitoes.
      Insecticidal activity of these compounds was limited to larval stages only.
      Highest activity of HOE 84498 was found against both Cx. tritaeniorhynchus and
      Anopheles culicifacies (LC50-0.0065 mg/I), MAT 9460 against Armigeres subalbatus
      (LC50-0.00043 mg/I) and Trebon against Cx. quinuefasciatus (LC50-0.00579 mg/I).
      Adulticidal effect was observed at higher dosages of 25-100 ug/cm2 of MAT 9460
      and HOE 84498 against all the species with LT50 ranging from 22.15-33.76 min. No
      appreciable residual effect was evident for the three compounds on the surfaces
      treated at the rate of 1-100 mg/m2 against any mosquito species.

PMID- 9163709
TI  - Antibiotic sensitivity of isolates of Pseudomonas aeruginosa in Buraidah, Saudi
      Arabia.
AB  - A study was carried out to determine the pattern of in vitro antibiotic
      sensitivity of a cross section of the isolates of Pseudomonas aeruginosa
      recovered from diverse clinical sources during a one year period. One hundred and
      eighty-six isolates were investigated by disc diffusion method employing
      multidiscs. Majority of the isolates were sensitive to amikacin (89.7%),
      tobramycin (75.81%), norfloxacin (68.48%), piperacillin (68.25%), and ceftazidime
      (58.81%). Other antibiotics were effective for a lesser number of isolates. A few
      isolates were simultaneously resistant to several antibiotics, viz. gentamicin,
      carbenicillin, tobramycin, ceftazidime and augmentin. The significance of the
      findings is discussed.

PMID- 9163710
TI  - Distribution of Phlebotomine sandflies (Diptera:Psychodidae) according to the
      physiographic divisions of India.
AB  - In this paper, the distribution of 44 known species of Phlebotomine sandflies
      which include vectors of leishmaniasis in India are arranged according to
      accepted physiographic divisions of India. Distribution maps in respect of known
      disease vectors Phlebotomous argentipes, P. papatasi, P. sergenti, P. salehi and
      potential vectors of leishmaniashis in India, P. hindustanicus and P. major are
      presented. The study brings out the salient features of sandfly distribution in
      India and need for more comprehensive work in the inadequately studied areas of
      the north east hills and the northern mountain ranges.

PMID- 9163711
TI  - Appropriate season for measles immunisation campaign in India.
AB  - Review of literature on the seasonality of measles in India reveals that measles
      occur throughout the year with peaks around March, while October-November are the
      low transmission months. The epidemics of measles however, occur any time during
      the year. Nevertheless, measles vaccination campaigns are carried out in India in
      the Month of March to increase the vaccine coverage levels. Being the low
      transmission season, October and November may be more appropriate for undertaking
      measles campaigns in India.

PMID- 9163712
TI  - Intestinal parasitism: a childhood problem in rural Bengal.
AB  - A study was undertaken to assess the parasitic infection rate in a rural
      community of West Bengal amongst children below four years of age suffering from
      gastrointestinal complaints. A total of 221 faecal samples were examined during
      November 1992 to April 1994. G. lamblia (17.2%) and E. histolytica (8.1%) were
      the predominant protozoas, whereas E. vermicularis (12.2%) and A. lumbricoides
      (8.1%) were found to be common amongst helminthic infection. A significantly
      lower infection rate was observed in children below one year (24.4 per cent) as
      compared to older age groups (66.4 per cent).

PMID- 9163714
TI  - Prevalence of bancroftian filariasis in Burdwan district, West Bengal: II. Vector
      and microfilariae density in colliery and non-colliery areas.
AB  - The paper reports the density of Culex quinquefasciatus, infection and
      infectivity rates, microfilariae(mf)- density and microfilaraemic persons in the
      colliery and non-colliery areas of Burdwan district, West Bengal. The numbers C.
      quinquefasciatus were significantly higher in colliery areas, as compared to non
      colliery areas. The infection rate and infectivity rates of the vector were found
      to be higher in colliery areas. The higher vector density in colliery area is one
      of the major reasons of higher prevalence of filariasis in that area. However,
      other environmental factors like exposure of the host to the coal might influence
      the pathogenesis of filariasis in the colliery area.

PMID- 9163713
TI  - An outbreak of viral hepatitis in Jodhpur city of Rajasthan.
AB  - An outbreak of Viral hepatitis occurred in Jodhpur city of Rajasthan during April
      to June, 1994. The attack rate was 3.04 per cent among 0-14 years age group and
      5.49% among the age group above 15 years, the overall attack rate being 4.5 per
      cent. Males were more affected than females. Epidemiological and serological
      findings suggest that the outbreak was due to enterically transmitted Non A Non B
      virus. The source of infection was drinking water contaminated with sewage.

PMID- 9163715
TI  - Plasma cholesterol, B-carotene and ascorbic acid changes in human malaria.
AB  - Serum cholesterol (Total and free) as well as B-carotene and vitamin C level
      concentrations during and after severe infection by Plasmodium falciparum were
      determined. The decrease in the concentrations of cholesterol and B-carotene
      during and after infection was not statistically significant (P > 0.01), while
      the decrease in vitamin C was statistically significant (P < 0.01) during and
      after infection.

PMID- 9163716
TI  - Malaria control in Jammu city, Jammu and Kashmir State.

PMID- 9163717
TI  - Microbial etiology and assessment of immunological status of children with
      persistent diarrhoea.

PMID- 9163718
TI  - Observations on susceptibility status of Phlebotomus argentipes to DDT in
      district South 24-Parganas, West Bengal.

PMID- 9163719
TI  - Isolation of RNA from blackcurrant (Ribes nigrum L.) fruit.
AB  - Extraction of high-quality RNA from blackcurrant fruit has hitherto proved
      difficult, probably owing to high levels of phenolic and polysaccharide
      components in the berries. The procedure described here is a modification of one
      described for grape berries, and yields RNA suitable for in vitro translations,
      RNA blot analysis, and cDNA library construction.

PMID- 9163720
TI  - Gene transfer by electroporation.
AB  - Electroporation of cells in the presence of DNA is widely used for the
      introduction of transgenes either stably or transiently into bacterial, fungal,
      animal, and plant cells. A review of the literature shows that electroporation
      parameters are often reported in an incomplete or incorrect manner, forcing
      researchers to rely too much on a purely empirical trial and error approach. The
      goal of this article is to provide the reader with an understanding of electrical
      circuits used in electroporation experiments as well as physical and biological
      aspects of the electroporation process itself. Further, a simple paradigm is
      provided which unites all electroporation parameters. This article should be
      particularly useful to those new to the technique.

PMID- 9163722
TI  - Probing protein folding and stability using disulfide bonds.
AB  - Disulfide bonds are required to stabilize the folded conformations of many
      proteins. The rates and equilibria of processes involved in disulfide bond
      formation and breakage can be manipulated experimentally and can be used to
      obtain important information about protein folding and stability. A number of
      experimental procedures for studying these processes, and approaches to
      interpreting the resulting data, are described here.

PMID- 9163723
TI  - Detection of single-copy genes in DNA from transgenic plants by nonradioactive
      Southern blot analysis.
AB  - Improvements to the sensitivity, speed, and reproducibility of digoxigenin (DIG)
      labeled probes and chemiluminescent substrates makes these compounds increasingly
      popular to detect nucleic acids. High sensitivity and low background are
      essential in Southern blot analysis, particularly with plant DNA. This article
      describes a nonradioactive system to detect single-copy genes in transgenic
      plants. Labeling using the polymerase chain reaction (PCR) was employed to
      produce highly sensitive and reusable DIG-labeled probes. The background was
      reduced by immobilizing the DNA onto nylon filters by alkaline transfer and by
      minimized gel handling; the signal-to-noise ratio was improved by modification of
      the detection procedure.

PMID- 9163724
TI  - Detection and identification of Listeria monocytogenes from milk and cheese by a
      single-step PCR.
AB  - Primers of iap gene were used as a target to develop a PCR technique for
      detecting Listeria monocytogenes in milk and cheese. The PCR technique gives good
      results in the detection of Listeria monocytogenes either in artificially or
      naturally contaminated foodstuffs and has a high sensitivity and specificity.
      Application of this rapid diagnostic tool could provide further information about
      the spread of L. monocytogenes in milk and cheese.

PMID- 9163721
TI  - In vivo versus in vitro screening or selection for catalytic activity in enzymes
      and abzymes.
AB  - The recent development of catalytic antibodies and the introduction of new
      techniques to generate huge libraries of random mutants of existing enzymes have
      created the need for powerful tools for finding in large populations of cells
      those producing the catalytically most active proteins. Several approaches have
      been developed and used to reach this goal. The screening techniques aim at
      easily detecting the clones producing active enzymes or abzymes; the selection
      techniques are designed to extract these clones from mixtures. These techniques
      have been applied both in vivo and in vitro. This review describes the advantages
      and limitations of the various methods in terms of ease of use, sensitivity, and
      convenience for handling large libraries. Examples are analyzed and tentative
      rules proposed. These techniques prove to be quite powerful to study the
      relationship between structure and function and to alter the properties of
      enzymes.

PMID- 9163725
TI  - Escherichia coli DnaA protein: the replication initiator.

PMID- 9163726
TI  - Effects of pleiotrophic mutations, degUh and spoOA, on the production of foreign
      proteins using the heterologous secretion system of Bacillus subtilis.
AB  - To elevate the production of foreign target proteins using a heterologous protein
      secretion system of Bacillus subtilis, two different pleiotrophic mutations,
      degUh for increase of transcriptional level of target genes and spoOA for
      reduction of extracellular protease activity of a host strain were introduced,
      respectively. The productivities of three differently originated enzymes, beta
      lactamase, streptokinase and human pancreatic trypsin inhibitor (hPSTI) were
      examined under the each mutation background. By the degUh mutation, the
      activities of all three enzymes secreted in the culture were increased, although
      the increased levels were different from 1.2-fold (streptokinase) to 1.8-fold
      (beta-lactamase). The lower productivity of streptokinase compared to other
      enzymes under the degUh background was caused by the higher susceptibility to
      proteolytic degradation. The increased transcriptional level of the beta
      lactamase gene by degUh mutation resulted in the accumulation of unprocessed
      precursor protein in the cytoplasm and cytoplasmic membrane. In the case of the
      spoOA mutation background, the differences in the levels of the secreted target
      proteins were not significant and observed only after a stationary phase of the
      growth.

PMID- 9163727
TI  - Characterization of viral inhibitory substance released from fused splenocyte.
AB  - The D variant of the encephalomyocarditis (EMC-D) virus is diabetogenic in mice
      by infecting and destroying pancreatic beta cells, but the EMC-B and EMC-DV
      viruses are not diabetogenic. We have presumed that the nondiabetogenicity of EMC
      B and EMC-DV is mainly caused by release of some viral inhibitory factors from
      lymphocytes or phagocytic cells. Mice were infected with EMC-B and their
      splenocytes were fused with myeloma cells. The splenocyte hybridoma 12D8 releases
      the viral inhibitory substance (VIS) which is neither immunoglobulin nor
      interferon. VIS has inhibitory effects against EMC-D in several kinds of cell
      lines, and against EMC-D, EMC-B, coxsackie B4, reovirus and the vesicular
      stomatitis virus in the L cell. VIS has a strong preventive effect (100%) against
      EMC-D induced diabetes in SJL/J mice and DBN/2N mice. In both pre- and post
      treatment studies, VIS remarkably decreased the incidence of both illness and
      death in SJL/J mice infected with the EMC-D virus. VIS, culture supernate itself
      of hybridoma, had viral inhibitory activities equivalent to 10(6)-10(7) IU/ml of
      interferon. VIS was very labile to heat (75% loss of activities at 37 degrees C
      for 18 h), stable only at pH 5-9, and precipitated at 50% (NH4)2SO4 solution. VIS
      activities existed in supernatant and pellet prepared from ultracentrifugation,
      but the properties of their activities could be differentiated quantitatively and
      qualitatively. It is speculated that VIS may be composed of at least two factors
      even though interferon may partially participate in one component of supernatant.
      The prevention and treatment effect of VIS on EMC-D infection in SJL/J mice might
      be due to the inhibition of the virus replication by VIS.

PMID- 9163728
TI  - Isolation and characterization of daunorubicin-resistant AML-2 sublines.
AB  - An attempt was made to isolate resistant sublines of acute myelogenous leukemia
      (OCI/ AML-2) cells by chronic exposure to gradually increasing concentrations of
      daunorubicin in order to determine the mechanism of its resistance to this drug.
      Four daunorubicin-resistant sublines, AML-2/D100, /D250, /D500, and /D1,000 were
      isolated. The values of relative resistance of each daunorubicin-resistant AML
      subline were about 3, 6, 18, and 23-fold, respectively, as compared to the AML-2
      line with an IC50 of 5 nM. The daunorubicin-resistant AML-2 sublines also showed
      cross resistance to various anticancer drugs including another anthracycline
      doxorubicin, a Vinca alkaloid vincristine, and an epipodophyllotoxin etoposide. A
      functional assay using flow cytometry showed decreased accumulation of
      daunorubicin in these sublines as compared to that of AML-2, which was reversed
      by cyclosporin A or cyanide. The development of the ATP-dependent multidrug
      resistant phenotype was due to low to high levels of expression of P-glycoprotein
      (PGP). The major mechanisms of increased PGP appears to be associated with gene
      amplification. In addition, other mechanisms such as increased stability of
      protein or mRNA might be involved depending on the concentration of daunorubicin
      used for selection. However, a multidrug resistance-associated protein (MRP) was
      not involved in these resistant sublines. These daunorubicin-resistant AML-2
      sublines could provide a useful model for the study of multidrug resistance
      mediated by PGP.

PMID- 9163729
TI  - Effect of a novel saponin adjuvant derived from Quillaja saponaria on the immune
      response to recombinant hepatitis B surface antigen.
AB  - Adjuvant activity of saponins extracted from the South American tree Quillaja
      saponaria has been demonstrated with many antigens. Recently, four saponin
      fractions (designated as QS-7, QS-17, QS-18, and QS-21) with adjuvant activity
      were purified by reverse phase chromatography. In particular, efficacy of the
      less toxic QS-21 fraction has been demonstrated with several recombinant viral
      antigens including HIV gp120. Here, we report a novel saponin fraction
      (designated as QS-L1) derived from Quillaja saponaria. Unlike previously
      identified saponins, QS-L1 had a different chemical structure and showed adjuvant
      activity only when administered in the presence of alum-precipitated antigen.
      Interestingly, the QS-L1 greatly increased not only a humoral immune response but
      also cellular immune response to recombinant hepatitis B virus surface antigen
      (HBsAg). Furthermore, QS-L1 showed lower toxicity in vivo and in vitro than the
      previously identified saponin fraction, QS-21. Finally, we examined the chemical
      structure of the QS-L1 using mass spectroscopic analysis, carbohydrate
      composition analysis and NMR spectroscopic analysis. Thus, our results indicated
      that this novel QS-L1 saponin fraction had several desirable properties required
      for an effective adjuvant.

PMID- 9163730
TI  - Prevalent and novel mutations of the tyrosinase gene in Korean patients with
      tyrosinase-deficient oculocutaneous albinism.
AB  - We analyzed the tyrosinase (TYR) gene of 12 Korean patients with various types of
      oculocutaneous albinism (OCA). We identified five different mutations in the TYR
      gene in 4 patients with severe OCA and in 2 patients with mild OCA, but found no
      mutations in the 6 patients with mild OCA phenotypes. Among the 5 mutations, a
      frameshift mutation, P310insC, was detected most frequently (allele frequency =
      0.5), and the other mutations were found less frequently, two of which, L288delT
      and IVS2-7t-->a,-10(-)-11deltt, are novel. This study may provide valuable
      information for the molecular diagnosis of and accurate genetic counseling for
      OCA1 in Koreans and perhaps other Asian groups.

PMID- 9163731
TI  - Identification of putative phosphoinositide-specific phospholipase C genes in
      filamentous fungi.
AB  - Five putative phosphoinositide-specific phospholipases C (PLC) genes were
      identified in three species of filamentous fungi. Using polymerase chain reaction
      with degenerate oligonucleotide primers, gene fragments encoding amino acid
      sequences homologous to PLCs of mammals and other organisms were amplified: one
      sequence from Botryotinia fuckeliana, one from Aspergillus nidulans, and three
      from Neurospora crassa. The molecular cloning and sequencing of a putative PLC
      gene (BCPLC1) from B. fuckeliana showed that it encoded a polypeptide containing
      X and Y domains, the two conserved regions found in all known PLCs. The
      hypothetical gene product of BCPLC1 was of delta type in its primary structural
      organization. The identification of three PLC genes in N. crassa shows that
      multiple PLC isozymes also occur in microbial eukaryotes.

PMID- 9163732
TI  - Chromosomal localization and neural distribution of voltage dependent calcium
      channel beta 3 subunit gene.
AB  - Voltage dependent calcium channel (VDCC) mediates the influx of free calcium ions
      that acts as a signal transducer. The beta 3 subunit of the VDCC regulates the
      activation (opening) and inactivation (closing) kinetics through
      phosphorylation/dephosphorylation. We isolated a genomic clone of the human VDCC
      beta 3 subunit from a human genomic DNA library using VDCC beta 3 cDNA as a
      probe. We localized VDCC beta 3 with this genomic DNA on the chromosome by
      fluorescent in situ hybridization, and the distribution of VDCC beta 3 in the
      nervous system was investigated in rats by in situ hybridization histochemistry
      with rat VDCC beta 3 cDNA. The gene for the VDCC beta 3 was specifically
      localized on human chromosome 12q13. The mRNA for the VDCC beta 3 was
      predominantly expressed in the nervous system. In the brain, a strong expression
      of VDCC beta 3 mRNA was found in the medial habenular nucleus, a high level of
      expression was observed in the olfactory bulb and cerebellum, and a relatively
      high level of VDCC beta 3 mRNA was localized in the cerebral cortex, caudate
      putamen and hippocampal formation. Interestingly, this distribution pattern is
      very similar to that of the rbE-II, mid-low VDCC 1 subunit, and it is suspected
      that VDCC beta 3 and rbE-II may function together as a pair.

PMID- 9163733
TI  - Sequence analysis, tissue expression and chromosomal localization of a mouse
      secreted superoxide dismutase gene.
AB  - Using a reverse transcriptase polymerase chain reaction (RT-PCR), a complement
      DNA encoding secreted superoxide dismutase (s-SOD) of a mouse kidney has been
      isolated and the nucleotide sequence was determined. The deduced amino acid
      sequence of mouse s-SOD cDNA shares 79% identity with the rat seminal SOD
      sequence and 61% identity with the human SOD3 sequence. Northern blot analysis
      showed that mouse s-SOD is intensely expressed in the kidney and lung tissues and
      detectable in other tested tissues, including the brain. The mouse s-SOD gene was
      assigned to chromosome 5 using fluorescence in situ hybridization analysis and
      PCR analysis of mouse/hamster hybrid cells.

PMID- 9163734
TI  - Expression of the fibroblast growth factor-2 gene during chick development.
AB  - In this report, we have carried out mRNA in situ hybridization analysis to study
      the pattern of expression of the fibroblast growth factor-2 (FGF-2) gene during
      chick development. The expression pattern of FGF-2 was compared to that of the
      fibroblast growth factor-1 (FGF-1) gene to further assess a possible role of the
      FGF-2 during chick embryogenesis. The whole embryos of various stages were
      examined with 35S-labeled riboprobes transcribed from the coding regions of chick
      FGF-2 and FGF-1 cDNAs. We show that the distribution pattern of FGF-2 mRNA was
      highly specific. The FGF-2 transcripts were localized to limb mesenchymes,
      pharyngeal regions, and embryonic kidneys in day 3 to day 6 chick embryos.
      However, no FGF-1 mRNA was detected in these structures indicating a unique role
      of FGF-2 in chick development. These results support the hypothesis that FGF-2
      may be a crucial signaling molecule during chick embryogenesis.

PMID- 9163735
TI  - Purification and characterization of an antifungal PR-5 protein from pumpkin
      leaves.
AB  - A 28-kDa antifungal PR-5 protein (PLTP) was purified from pumpkin leaves to
      homogeneity by using ammonium sulfate fractionation, a regenerated chitin column,
      and reversed-phase column chromatographies on butyl-Toyopearl and HPLC C18
      columns. Analysis of 14 N-terminal amino acid sequences of PLTP shows 100%
      sequence identity to those of two PR-5 proteins, NP24 from tomatoes and AP24 from
      tobacco. The identical sequence also exhibited high amino acid sequence homology
      to that of an osmotin-like protein (OLP; 71%) from tobacco cells and thaumatin
      (64%), a sweet-tasting protein of Thaumatococcus danielli Bench. When the PLTP
      was immuno-blotted with antiserum raised against the tobacco OLP, the OLP
      antibody specifically cross-reacted with the PLTP, suggesting that they share
      several common epitopes in their tertiary structure of the proteins. The purified
      PLTP rapidly lyzed hyphal tips of Neurospora crassa at a concentration greater
      than 200 nM and significantly inhibited the fungal growth of Fusarium oxysporum
      in an agar-disc plate at a concentration greater than 2 microM. It also shows a
      synergistic effect with nikkomycin, a chitin synthase inhibitor, for the growth
      inhibition of Candida albicans.

PMID- 9163736
TI  - Rapid analysis for the isolation of novel genes encoding putative effectors to
      the position-specific regulatory element of murine Hoxa-7.
AB  - Hox genes are known to play a critical role in pattern formation during
      vertebrate development by being expressed at the specific time and in the
      specific position along the antero-posterior body axis. In order to understand
      the regulatory mechanism for the position-specific expression of murine Hoxa-7,
      yeast one-hybrid system was applied. DNA fragment conferring a position
      specificity to the Hoxa-7 gene was placed just upstream from the yeast CYC1
      promoter and lacZ gene in a reporter. Selection of LacZ positive clones after
      cotransformation of the reporter and mouse embryonic cDNA library as an effector,
      which was designed to be expressed as fusion proteins to the GAL4 activation
      domain, allowed us to isolate putative factors interacting with the position
      specific regulatory element of murine Hoxa-7. A total of 28 positive clones were
      screened from 5 x 10(5) yeast transformants. About 70% of the clones turned out
      to be novel and most of the candidate clones selected in this study showed a
      temporally restricted expression pattern during embryonic development, suggesting
      that this method could provide an efficient way for isolating novel genes whose
      expressions are temporally regulated during embryogenesis.

PMID- 9163737
TI  - Molecular characterization of a rab-related small GTP binding protein cDNA from
      rice (Oryza sativa L. IR-36).
AB  - To study physiological roles of plant small GTP binding proteins, we isolated a
      cDNA clone (ORrab2) encoding the rab-related small GTP binding protein from rice
      (Oryza sativa L. IR-36) by using human cDNA rab2 as a probe. The deduced amino
      acid sequence of the ORrab2 gene shared all the conserved regions, important for
      GTPase/GTP binding activities, with those of other small GTP binding proteins.
      ORrab2 is a 1028 bp long cDNA, encodes a 23.2 kDa protein which shows 85.2%
      similarity on the amino acid sequence level to the Hrab2 protein, and was used as
      a probe. Through Southern and Northern blot analyses, we found that ORrab2 is a
      single copy gene and actively expressed at the stages of cell division and
      elongation. We investigated GTP binding abilities by a filter assay procedure.
      Deletion of a binding motif, GDTGVGKS, within an ORrab2 protein showed a
      significant decrease of GTP binding affinity, suggesting its important role in
      nucleotide binding.

PMID- 9163738
TI  - Cloning, sequencing, and overexpression of SH2/SH3 adaptor protein Nck from mouse
      thymus.
AB  - Nck, an oncogenic protein containing one SH2 and three SH3 domains, is a common
      target for phosphorylation by a variety of cell surface receptors. The absence of
      a recognizable catalytic domain of Nck suggests that Nck serves as a linker
      molecule to couple cell surface receptors to downstream effector molecules that
      regulate cellular responses induced by receptor activation. In this study, we
      isolated Nck cDNA from mouse thymus by screening a phase expression library using
      monoclonal antibody (mAb) B16-5 which recognizes the SH3 domain of phospholipase
      C-gamma 1. Nck protein was purified from an extract of the Sf9 cell that had been
      infected with recombinant baculovirus containing mouse Nck cDNA. The purified
      protein exhibited an apparent molecular mass of 47 kDa on SDS-polyacrylamide
      gels. Nck antibody was generated in rabbits using purified protein as an antigen.
      The distribution of Nck protein in rat tissues examined by immunoblots showed
      that Nck is expressed widely, and that brain, spleen, and tests contain more Nck
      than other tissues examined.

PMID- 9163739
TI  - Reassembly and reconstitution of separate alpha and beta chains of human
      leukocyte antigen DR4 molecule isolated from Escherichia coli.
AB  - The class II major histocompatibility complex molecules play a major role in
      presentation of exogenous antigenic peptides to the CD4 positive helper T cell.
      These are heterodimeric cell surface glycoproteins consisting of alpha- and beta
      chains. In the present study, we cloned and expressed the alpha- and beta-chain
      of HLA-DR4 lacking the transmembrane and cytoplasmic domain separately in
      Escherichia coli using the pET-5a expression vector system. The expressed alpha-
      and beta-chains were purified in a denaturing condition by an ion exchange
      chromatography on Q-Sepharose and a gel filtration chromatography on Sephacryl S
      200, respectively. The recombinant proteins were refolded and reassembled by
      removing the denaturing agent and concomitant reoxidation of the disulfide bond.
      The refolded heterodimeric rDR4 molecule was resolved by 12.5% SDS-PAGE in a
      nonreducing condition and confirmed by Western blot using polyclonal antibody
      against DR-alpha and the monoclonal antibody (L243) for the conformationally
      correct DR molecule. The rDR4 molecules were reconstituted with a 50-fold molar
      excess biot-HA (307-319), and the bound peptides to the heterodimer complex were
      determined by a microplate assay coated with L243 antibody using Extravidin-HRP
      conjugate.

PMID- 9163740
TI  - Primers determine the sensitivity of PCR-mediated hepatitis B virus DNA detection
      and pretreatment of PCR mixture with 8-methoxypsoralen eliminates false-positive
      results.
AB  - Most methods for the diagnosis of hepatitis B virus (HBV) infection largely
      depend on viral DNA detection by polymerase chain reaction (PCR) or
      radioimmunological assay of viral antigens or antibodies. The quality assurance
      program recently established in Europe reported that PCR-mediated HBV DNA
      detection methods used in many laboratories produced a high rate of false
      positive and false-negative results. Thus, we attempted to improve the conditions
      of current PCR methods for detection of HBV DNA. In the present study, we applied
      a recently developed method of releasing HBV DNA from virion by NaOH treatment of
      patient serum. Using four different primer sets specific to the HBV core region,
      we found that the sensitivity of first-round PCR can be improved by more than two
      orders of magnitude depending on the primers. The second round of PCR using
      nested primers was sensitive enough to detect up to 10(-6) pg of the HBV DNA,
      which is equivalent to approximately 3 copies of the HBV genome. Among the
      approximately 800 HBV-infected patient sera investigated in our laboratory, more
      than 60% of the tested samples gave positive results in the first-round PCR. The
      rate of positive results obtained using our experimental conditions is very high
      in comparison with other reports. The reamplification of the first-round PCR
      reaction mixture with the nested primers produced practically 100% positive
      results. For diagnosis of HBV infection, we routinely used 1 microliter of
      patient serum, which was found to be optimum in our laboratory. Surprisingly,
      from 20% of our positive results, even serum diluted to 1/100 (0.01 microliter)
      produced a stronger signal than 1 microliter. This observation suggests that
      direct PCR amplification of HBV DNA released from serum by NaOH treatment has to
      be compensated by other DNA detection methods for correct quantitation. In order
      to eliminate the false positive signal resulting from the carry-over due to
      massive screening of a large number of samples, PCR reaction mixture containing 8
      methoxypsoralen was exposed to ultraviolet light prior to thermal cycle
      amplification. This exercise did not decrease the sensitivity of the detection
      method, but almost completely removed the false positive results caused by
      contaminated templates. We are in the process of improving PCR-mediated HBV DNA
      detection methods to attain more reliable and easily applicable methods.

PMID- 9163741
TI  - Crystal structure of thermostable alpha-amylase from Bacillus licheniformis
      refined at 1.7 A resolution.
AB  - alpha-Amylases (alpha-1,4-glucan-4-glucanohydrolase, E.C.3.2.1.1) catalyze the
      cleavage of alpha-1, 4-glucosidic linkages of starch components, glycogen, and
      various oligosaccharides. Thermostable alpha-amylases from Bacillus species are
      of great industrial importance in the production of corn syrup or dextrose.
      Thermostable alpha-amylase from Bacillus licheniformis, a monomeric enzyme with
      molecular mass of 55,200 Da (483 amino acid residues), shows a remarkable heat
      stability. This enzyme provides an attractive model for investigating the
      structural basis for thermostability of proteins. The three-dimensional structure
      of thermostable alpha-amylase from Bacillus licheniformis has been determined by
      the multiple isomorphous replacement method of X-ray crystallography. The
      structure has been refined to a crystallographic R-factor of 19.9% for 58,601
      independent reflections with F0 > 2 sigma F0 between 8.0 and 1.7 A resolution,
      with root mean square deviations of 0.013 A from ideal bond lengths and 1.72
      degrees from ideal bond angles. The final model consists of 469 amino acid
      residues and 294 water molecules. Missing from the model are the N- and C-termini
      and the segment between Trp182 and Asn192. Like other alpha-amylases, the
      polypeptide chain folds into three distinct domains. The first domain (domain A),
      consisting of 291 residues (from residue 3 to 103 and 207 to 396), forms a
      (beta/alpha)8-barrel structure. The second domain (domain B), consisting of
      residues 104 to 206, is inserted between the third beta-strand and the third
      alpha-helix of domain A. The third C-terminal domain (domain C), consisting of
      residues 397 to 482, folds into an eight-stranded antiparallel beta-barrel.
      Neither calcium ion nor chloride ion is located near the active site. This study
      reveals the architecture of the thermostable alpha-amylase from Bacillus
      licheniformis. By homology with other alpha-amylases, important active site
      residues can be identified as Asp231, Glu261, and Asp328, which are all located
      at the C-terminal end of the central (beta/alpha)8-barrel. Since many of the
      stabilizing and destabilizing mutations obtained so far fall in domain B or at
      its border, this region of the enzyme appears to be important for
      thermostability. The factors responsible for the remarkable thermostability of
      this enzyme may be increased ionic interactions, reduced surface area, and
      increased packing interactions in the interior.

PMID- 9163742
TI  - DNA methylation patterns and sequence transitions of the CpG island of mouse Hprt
      during early embryogenesis.
AB  - The timing and pattern of methylation of the CpG island in the X-chromosome gene,
      Hprt, was examined using bisulfite methods to assess the occurrence of DNA
      cytosine methylation at the onset of X-chromosome inactivation (XCI). The Hprt
      sequences were extensively methylated in 4.5 dpc blastocysts, and the levels of
      methylation progressively decreased to 7.5 dpc. Adult patterns of methylation
      were established in the embryonic tissues after 7.5 dpc. By contrast, methylation
      continued to decrease in extraembryonic lineages and at 13.5 days was not
      detectable on the paternal Hprt sequences in the yolk sac endoderm. In the
      bisulfite-treated coding strand, numerous G to A transitions and CpTpG
      methylations were observed that were unique to the methylated or nonmethylated
      Hprt sequences, respectively, in early development.

PMID- 9163743
TI  - Cloning and analysis of the DNA polymerase-encoding gene from Thermus caldophilus
      GK24.
AB  - The gene encoding Thermus caldophilus GK24 (Tca) DNA polymerase was cloned into
      Escherichia coli using the structural gene coding for Thermus aquaticus YT-1
      (Taq) DNA polymerase as a hybridization probe. The nucleotide sequence of the
      cloned DNA was determined. The primary structure of the Tca DNA polymerase was
      deduced from the nucleotide sequence. The Tca DNA polymerase comprised 834 amino
      acid residues and its molecular mass was determined to be 93,810. On alignment of
      the whole amino acid sequence, Tca DNA polymerase showed a high sequence homology
      with the E. coli DNA polymerase I-like DNA polymerases, and 86% identity with Taq
      DNA polymerase, 38% with E. coli and Streptococcus pneumoniae (Spn) DNA
      polymerase I. An extremely high sequence identity was observed in the region
      containing the polymerase activity. The codon usage in the Tca DNA polymerase
      gene was in fact similar to the characteristic usages in the genes for proteins
      from bacteria of genus Thermus: the G+C content in the third position of the
      codons was as high as 93%. The Tca DNA polymerase gene was expressed under the
      control of tac promoter on a high copy plasmid, pTCA in E. coli.

PMID- 9163744
TI  - Heparin binding of laminin: contribution of the triple helix in the rod domain to
      the formation of cryptic and active sites in the globular domain.
AB  - Laminin, a multidomain glycoprotein in basement membranes, interacts with heparin
      through the terminal globular domain (G domain) of its long arm. The interaction
      with heparin is thought to be important for modulation of basement membrane
      assembly and adhesion to cells. The G domain contains two different heparin
      binding activities: a strong one in the proximal portion and a moderate one in
      the distal portion of globule. The proximal activity was found to be weak in
      fragment E8 and in the intact laminin long arm, whose three-chain moieties are
      joined together in a triple-helical coiled-coil. Dissociation of the A chain of
      E8 from its B chain moieties by denaturation and chain separation resulted in the
      exposure of heparin binding activity the in the globular domain. Furthermore,
      when a recombinant G domain with a distal alpha-helical domain was intercalated
      into the B chains of E8, the triple alpha-helix was reconstituted and heparin
      binding was considerably reduced. This data provides evidence for the influence
      of non-heparin binding rod domain on the binding activity in the G domain.

PMID- 9163745
TI  - Isolation and characterization of a processed pseudogene for murine cyclin D3.
AB  - By using radiolabeled murine cyclin D3 cDNA as a probe, two cyclin D3 genomic
      clones, MCD3P-117 and MCD3P-327, were isolated from a murine genomic library
      constructed with murine liver DNA. Physical mapping and DNA sequence analysis
      revealed that these clones contain approximately 1.5 kb uninterrupted linear
      sequence similar to murine cyclin D3 cDNA, indicating that the 1.5 kb sequence is
      a processed pseudogene for cyclin D3. When the nucleotide sequence of the cyclin
      D3 pseudogene was compared with that of cyclin D3 cDNA at the nucleotide level,
      the pseudogene contained 229 bp of 5'- and 371 bp of 3'-untranslated regions, and
      a recognizable complete coding region that is 90% identical to murine cyclin D3.
      This sequence is bounded by the repeat sequence (GC/AGCTCTCC), which is common to
      many processed pseudogenes. However, multiple genetic lesions, including
      substitution, deletion and/or insertion events that result in modification of the
      reading frame were found in the pseudogene sequence. The pseudogene appeared to
      accumulate 67 random point mutations in the functional coding region composed of
      879 nucleotide positions. It is thus estimated that the cyclin D3 pseudogene
      arose approximately 11 million years (Myr) ago. These data provide the first
      characterization of murine cyclin D3 pseudogene and insight into its evolutionary
      age.

PMID- 9163746
TI  - Cloning of an E. coli RecA and yeast RAD51 homolog, radA, an allele of the uvsC
      in Aspergillus nidulans and its mutator effects.
AB  - An E. coli RecA and yeast RAD51 homolog from Aspergillus nidulans, radA, has been
      cloned by screening genomic and cDNA libraries with a PCR-amplified probe. This
      probe was generated using primers carrying the conserved sequences of eukaryotic
      RecA homologs. The deduced amino acid sequence revealed two conserved Walker-A
      and -B type nucleotide-binding domains and exhibited 88%, 60%, and 53% identity
      with Mei-3 of Neurospora crassa, rhp51+ of Schizosaccharomyces pombe, and Rad51
      of Saccharomyces cerevisiae, respectively. radA null mutants constructed by
      replacing the whole coding region with a selection marker showed high methyl
      methanesulfonate (MMS) sensitivity. Heterozygous diploids of radA disruptant with
      the uvsC114 mutant failed to complement with respect to MMS-sensitivity,
      indicating that radA is an allele of uvsC. In selecting spontaneous forward
      selenate resistant mutations, mutator effects were observed in radA null mutants
      similarly to those shown in uvsC114 mutant strains.

PMID- 9163747
TI  - Cloning and characterization of the citA gene encoding the mitochondrial citrate
      synthase of Aspergillus nidulans.
AB  - We isolated a citrate synthase gene (citA) from Aspergillus nidulans. By analysis
      of the protein coding region, citA was shown to encode a citrate synthase (CitA)
      of 52.2 kDa consisting of 474 amino acid residues that were interrupted by seven
      introns. Also, the precursor CitA protein was revealed to have an N-terminal
      mitochondrial targeting signal of 35 amino acid residues containing an R-3
      cleavage motif, R(32)-C-Y decreases S(35), which supports the fact that citA
      encodes the mitochondrial form of citrate synthase of A. nidulans. Southern blot
      analysis showed that citA is present as a single copy in the genome.

PMID- 9163748
TI  - Stabilization by glycinebetaine of photosynthetic oxygen evolution by thylakoid
      membranes from Synechococcus PCC7002.
AB  - Active thylakoid membranes were prepared from Synechococcus PCC7002 in a medium
      that contained glycinebetaine. The oxygen-evolving activity of photosystem II of
      these thylakoid membranes was enhanced and stabilized by the presence of
      glycinebetaine. The heat stability of the oxygen-evolving activity of the
      thylakoid membranes was also enhanced by glycinebetaine.

PMID- 9163749
TI  - Molecular cloning and sequence analysis of a putative ras gene of the
      phytopathogenic fungus Botryotinia fuckeliana.
AB  - We solated and determined the complete nucleotide sequence of a ras gene from
      Botryotinia fuckeliana, the causal agent of gray mold disease. Furthermore, in
      two other phytopathogenic fungi, Magnaporthe grisea (rice blast fungus) and
      Colletotrichum lagenarium (an anthracnose fungus), ras gene homologs were
      identified by amplifying gene fragments in polymerase chain reactions. The
      putative ras gene of B. fuckeliana encoded a polypeptide of 212 amino acids, and
      the coding sequence was interrupted by three short introns. The amino-terminal
      one third of the predicted Ras protein was highly homologous, and the next one
      third moderately homologous, to those of mammalian Ras proteins. The carboxy
      terminal one third showed no homology, except in the last several amino acids
      that conformed to the acylation consensus.

PMID- 9163750
TI  - [Proceeding of the 70th annual meeting of the Japanese Orthopedic Association.
      Sapporo, Japan. June 19-22, 1997. Abstracts I].

PMID- 9163751
TI  - [Proceedings of the 70th annual meeting of the Japanese Orthopedic Association.
      Sapporo, Japan. June 19-22, 1997. Abstracts II].

PMID- 9163753
TI  - [Epilepsy from the viewpoint of clinical neurophysiology].

PMID- 9163752
TI  - [Surgical pathology of intractable epilepsy: with a reference to cerebral
      malformation].

PMID- 9163754
TI  - [Epilepsy and Child Neurology].

PMID- 9163755
TI  - [Treatment of epilepsy by neurological surgery].

PMID- 9163757
TI  - [Locations of crossover breakpoints within the CMT 1 A-REP repeat in patients
      with hereditary neuropathy with liability to pressure palsy--detection by
      recombinant chromosome-specific polymerase chain reaction].
AB  - The crossover breakpoints for hereditary neuropathy with liability to pressure
      palsies (HNPP) are located in the CMT 1 A-REP repeat flanking a 1.5 Mb region of
      chromosome 17p11.2-12. Three-unrelated HNPP patients have breakpoints in a 3.2 kb
      novel fragment of recombinant chromosome in the CMT 1 A-REP repeat. The fragment
      is detected by recombinant chromosome-specific polymerase chain reaction (PCR).
      Further analysis of PCR demonstrated a 1.2 kb novel junction fragment in the 3.2
      kb region in all HNPP patients. The precise mapping of the breakpoints indicated
      that 2 patients were localized in a 700 bp interval of the 1.2 kb fragment 1.3kb
      telomeric to a marier transposon-like element (Kiyosawa and Chance, HMG 5: 745
      753, 1996), suggesting that this region is a recombinational "hotspot" within the
      CMT 1 A-REP repeat for HNPP as well as CMT 1 A.

PMID- 9163756
TI  - [Clinical classification of ALS patients based on the total course of ALS-
      proposal of respiratory motor paralysis-preceded type and its significance].
AB  - Since the motor paralysis occurs in all motor systems in ALS, the
      clinicopathological findings and care of the patients living beyond the
      development of respiratory failure must be considered. We have divided the
      efferent motor systems into four groups, i.e., limb, bulbar, respiratory, and
      external ocular. In this study, 37 ALS patients were followed for more than two
      years with respirator, and the onset of motor paralysis in all four systems was
      observed in each patient. First, we classified the patients into three groups
      according to the number of paralyzed motor systems observed within six months
      from the onset of the first motor paralysis, and we discuss the patient's
      prognosis after the first motor paralysis. Twenty-one patients with paralysis of
      the respiratory motor system alone were categorized as respiratory paralysis
      preceded type ALS (R-type ALS), four patients with paralysis of the bulbar motor
      system alone as bulbar paralysis-preceded type ALS (B-type ALS), and 12 patients
      with simultaneous paralysis of two or more motor systems as combined motor system
      paralysis type ALS (C-type ALS). The results showed that the prognosis of R-type
      ALS is slow progression and that of C-type ALS, rapid progression. Next, we
      investigated the time of occurrence of the first motor paralysis of the four
      motor systems in 37 patients, and we discuss the most vulnerable motor functions
      in ALS, i.e., the initial clinical presentations in ALS. The most frequent first
      motor paralysis was of the respiratory motor system, and the initial clinical
      manifestations in ALS were impairment of fine discriminating voluntary
      respiratory and limb motor functions. These findings could be explained by the
      rule of ALS involvements, according to which onto-genetically newer motor
      functions are lost earlier than the older ones. Based on the findings in this
      study, we concluded that ALS initially involves the ontogenetically new motor
      functions in "the first system" proposed by G. Holstege, whose anatomical
      structure is composed of pre-motoneurons and motoneurons in the brain stem and
      spinal cord.

PMID- 9163758
TI  - [An autopsied case doubly infected by mucor mycelia and herpes simplex virus-2 in
      the remission state after bone marrow transplantation for acute myelogenous
      leukemia].
AB  - A 36-year-old woman who had been in complete remission after bone marrow
      transplantation against her leukemia presented with visual disturbance and
      cerebellar signs. She showed unusual involuntary movement as if she rolled a ball
      of string, and died two months after the onset of illness. Necropsy revealed
      hemorrhagic and necrotic lesions in the thalamus, basal ganglia, cerebellar
      dentate nucleus, superior colliculus, midbrain pretectum and red nucleus, and
      mucor mycelia were numerously found. HSV-2 immunoreactivity was found in both
      astroglial and oligodendroglial perikaraya. These hemorrhagic-necrotic lesions
      were partly associated with HSV-2 infection, but it was difficult to discriminate
      those from mucormycotic lesions. The unusual involuntary movement was considered
      to be due to basal ganglia lesions. This case was double infection by mucor
      mycelia and HSV 2, and clinicopathological consideration was described.

PMID- 9163759
TI  - [A case of frontal gait apraxia caused by hypoxic encephalopathy].
AB  - We reported a rare case who had hypoxic-encephalopathy causing frontal apraxia of
      gait. The patient, a 34-year-old female, was admitted in July, 1994, complaining
      of difficulty in walking after anoxic brain damage caused by ventricular
      arrhythmia. She had difficulty in raising her feet, which appeared to be rooted
      to the floor. There was no evidence of motor paralysis, spasticity, rigidity or
      sensory loss, but she did show frontal lobe signs such as foot grasp reflex and
      Gegenhalten. Cranial MRI showed slight atrophy of the frontal lobe. On T2
      weighted image, high-intensity areas were detected at the posterior internal
      capsule and corona radiata. Single photon emission CT (123I-IMP) demonstrated a
      low perfusion area which included the inferomedical part of the frontal lobe.
      After 8 months of hospitalization, her postural instability and unsteady gait
      slowly improved without treatment as frontal signs such as foot grasp reflex
      disappeared. We speculate that her apraxia of gait may result from grasp reflex
      and Gegenhalten.

PMID- 9163760
TI  - [Familial Creutzfeldt-Jakob disease with the heterozygous point mutation at codon
      200 of the prion protein gene (Glu-->Lys)--report of CJD200 brothers of Yamanashi
      Prefecture origin].
AB  - We report two brothers with familial Creutzfeldt Jakob disease (CJD) having a
      heterozygous point mutation at codon 200 of the prion protein gene (Glu-->Lys):
      CJD200. The brothers were born in Kitakoma-gun, Yamanashi Prefecture. Patient 1,
      a 62-year-old man, developed CJD in 1995 and died nine months later. Patient 2,
      his brother, developed CJD200 at the age of 58 in 1982 and died 13 months later.
      They both exhibited rapidly progressive dementia with myoclonus and periodic
      synchronous discharges on electroencephalograms and became bedridden with three
      or four months. DNA analysis of peripheral blood cells of patient I showed a
      point mutation in the prion protein gene at codon 200: GAG-->AAG (Glu-->Lys).
      Five families with CJD200, 11 patients, have been reported in Japan to date, and
      nine of the patients from four families were born in Yamanashi Prefecture and
      vicinity. Our patients were born in the same area. We suspect that there is a
      cluster of CJD200 in Yamanashi Prefecture and vicinity. In Europe and America the
      phenotype of CJD200 has been reported to be heterogeneous, whereas the clinical
      features in Japanese cases are fairly homogeneous. We suspect that these patients
      have a common ancestor with a codon 200 mutation, and that that explains why the
      phenotypes are homogeneous.

PMID- 9163762
TI  - [Pituitary apoplexy].

PMID- 9163761
TI  - [Juvenile cerebral infarction with familial hyperlipoproteinemia (a)--case
      report].
AB  - A 34-year-old male with a history of angina pectoris suddenly developed weakness
      in the right upper and lower limbs, and consulted our hospital. Computed
      tomography (CT) and magnetic resonance imaging (MRI) suggested cerebral
      infarction. Cerebral angiography revealed stenosis at the M1 portion of the left
      middle cerebral artery. Hypertension, diabetes, tobacco or hyperlipidemia were
      not considered as risk factors for cerebral infarction. The lipoprotein (a)
      [Lp(a)] level was high. In the present case, medication with a nicotinic acid
      agent, niceritrol, for hyperlipoproteinemia and low density lipoprotein (LDL)
      apheresis were performed. Concerning family history, the patient's mother and
      younger sister had hyperlipoproteinemia. Recent studies have reported that
      increased Lp(a) levels are an independent risk factor even in cerebral infarction
      and coronary artery disease. Measurement of Lp(a) levels and treatment for
      increased Lp (a) levels may be important.

PMID- 9163763
TI  - [A 29-year-old man with diabetes insipidus and cerebellar ataxia and development
      of spinal cord swelling 15 years after the onset].
AB  - We report a 29-year-old man with diabetes insipidus and cerebellar ataxia who
      developed spinal cord swelling 15 years after the onset. He was well until 14
      years of the age when he noted dizziness. Two years after there was an onset of
      gait disturbance and slurred speech. He also noted polydipsia and polyuria. He
      was evaluated at the neurosurgery service of our hospital when he was 17 years of
      the age. Neurologic examination at that time revealed memory loss, horizontal
      nystagmus, cerebellar ataxic gait, dysmetria and decomposition more on the left.
      Cranial CT scan revealed a mass lesion involving the left subthalamic region and
      the head of the caudate area. Spinal fluid was unremarkable, however, human
      chorionic gonadotropin was increased to 27 mIU/ml. He was treated by radiation
      therapy (3,000 rads for total brain area and 5,460 rads for focal region). His CT
      scan and memory loss improved, however, cerebellar ataxia was unchanged. Three
      years after the radiation, he started to show choreic movement in his neck and
      left upper extremity. He was admitted to our service in August 14, 1995 when he
      was 29 years of the age. On admission, he was alert but disoriented to time;
      calculation was also poor. Higher cerebral functions were intact. The optic fundi
      were normal without papilledema. Visual field appeared intact. Gaze nystagmus was
      observed in all the directions, but more prominent in the horizontal direction.
      Speech was slurred. Otherwise, cranial nerves were unremarkable. Motor wise, he
      showed marked truncal and gait ataxia; he was unable to walk because of ataxia.
      Muscle atrophy and marked weakness was noted in both upper extremities more on
      the left side. Deep tendon reflexes were diminished in the upper extremities but
      active in the lower extremities. He was polyuric; urinary specific gravity was
      low. Spinal fluid contained 6 cells/cmm and 113 mg/ dl of protein; Queckenstedt
      was positive. MRI revealed swelling of the cervical cord; in addition, the entire
      cervical region and the medullar oblongata appeared as high signal intensity
      areas. No mass lesion was noted in the supratentorial structures but the third
      ventricle was markedly enlarged. Surgical biopsy was performed on the cervical
      lesion. The patient was discussed in neurologic CPC, and the chief discussant
      arrived at the conclusion that the patient had germinoma with
      syncytiotrophoblastic giant cells in the diencephalic region which appeared to
      have been cured by radiation therapy; he thought that the cervical lesion was the
      seeding of germinoma. Cerebellar ataxia was ascribed to the remote effect of
      germinoma. Most of the participants thought that the original tumor was germinoma
      and the cervical lesion was its spread. Some participants thought that his ataxia
      was caused by germinoma cells involving the medulla and the inferior cerebellar
      peduncles. Histologic observation of the biopsied tissue from the spinal cord
      revealed the typical two cell patterned germinoma. Most of the tumor cells were
      not stained for an antibody against HCG, but some tumor cells were positively
      stained. Germinoma is very radio-sensitive; this patient showed T2 high signal
      lesion involving the medulla oblongata and cervical cord continuously. Probably,
      tumor cells in the lower brain stem escaped radiation, and gradually spread to
      the spinal cord over many years. At the time of operation, the surface of the
      spinal cord was free from tumor cells. Therefore, tumor cells invaded the spinal
      cord continuously from the medulla oblongata. He was treated with cervical
      radiation, and his neurologic as well as radiologic findings showed marked
      improvement.

PMID- 9163764
TI  - Pathogenesis of endometriosis.
AB  - This article reviews the pathogenesis of endometriosis, which involves retrograde
      dissemination of endometrium and/or development in situ by metaplasia, and there
      is evidence suggesting that genetic and hormonal factors may play a role. There
      is also substantial evidence that immunologic factors, namely peritoneal
      macrophages, T cells, natural killer cells, and soluble products secreted by
      these cells, are involved in the pathogenesis of endometriosis.

PMID- 9163765
TI  - Epidemiology of endometriosis.
AB  - This article summarizes present knowledge about the epidemiology of
      endometriosis. Surprisingly, little is known about the prevalence or risk factors
      of endometriosis, given the medical care and employment costs. Knowledge about
      the epidemiology of endometriosis is hampered by the inability to diagnose this
      disease in the general population. Based on a single cohort study, it is
      estimated that there is a 10% prevalence of endometriosis in the general
      population. Age is the only sociodemographic characteristic for which a
      consistent positive relationship has been observed. In general, the risk of
      endometriosis appears to increase for reproductive health factors that may relate
      to increased exposure to menstruation (i.e., shorter cycle length, longer
      duration of flow, or reduced parity). The risk appears to decrease for personal
      habits that may relate to decreased estrogen levels (i.e., smoking, exercise).

PMID- 9163766
TI  - Pathophysiology. The biologic principles of disease.
AB  - Endometriosis, although associated with a large variety of symptoms, primarily
      produces pain and infertility; however, the strong correlation with these
      disorders, along with basic questions as to why endometriosis develops, when does
      it become a disease status, and why it's associated with symptoms such as pain or
      infertility, are still not well understood. A better understanding of the
      relationship between disease and symptoms of endometriosis must be acquired if
      effective progress in the treatment of pain and infertility related to
      endometriosis is to be made.

PMID- 9163767
TI  - Basic research in endometriosis.
AB  - A more thorough understanding of the mechanisms associated with the cause and
      pathophysiology of endometriosis may help in the development of new diagnostic
      and therapeutic methods for the management of endometriosis. Research has begun
      to enhance our understanding of endometriosis by demonstrating the differences
      and similarites between eutopic and ectopic endometrium, and by characterizing
      the peritoneal environment. Animal models have been developed and validated to
      conduct studies that are ethically impossible in women. Recently, cell culture
      models, using purified populations of cells from endometriotic lesions, have
      provided an appropriate in vitro endometriosis model to study the language by
      which cells communicate; to evaluate the biochemical effects of steroids, growth
      factors, pharmacological agents and immunomodulatory agents on the cells; and to
      study the effects of endometriosis on reproduction.

PMID- 9163768
TI  - Immunology and endometriosis. Fact, artifact, or epiphenomenon?
AB  - Endometriosis is a complex and intriguing disease. If retrograde menstruation
      normally occurs, then why do all women not develop endometriosis? The exact
      prevalence of endometriosis is unknown; however, a 20% to 90% prevalency rate has
      been reported in women with pelvic pain and infertility. This article reviews the
      factors involved.

PMID- 9163769
TI  - Environmental toxins and endometriosis.
AB  - The effect of natural, environmental, or manufactured substances on endocrine
      organs is a current topic of discussion. Recently, some toxicants have been
      suggested to promote endometriosis; therefore, attention has turned to the role
      of environmental factors as a stimulant for endometriosis growth and maintenance.
      This article reviews the influence of various toxicants on endometriosis.

PMID- 9163770
TI  - Diagnosis of endometriosis.
AB  - Diagnosis of endometriosis requires careful interpretation of objective surgical
      and pathologic findings in the context of the patient's clinical presentation.
      Clinical assessment helps to identify patients at high risk of endometriosis and
      selects those who warrant further testing. Determination of the serum level of CA
      125, and to a lesser extent, other proteins, may be helpful in evaluating
      selected population at risk and following the course of the disease. Selective
      use of imaging studies, especially ultrasound and magnetic resonance imaging, may
      also be helpful. Ultimately, the diagnosis of endometriosis is usually confirmed
      or refuted by laparoscopy, preferably performed in conjunction with histologic
      evaluation of excised lesions.

PMID- 9163771
TI  - Classification of endometriosis.
AB  - The evolution of classification schemes for endometriosis has continued since the
      1920s, when initial attempts were made to describe endometriosis. The cause,
      pathophysiology, and natural history of endometriosis remain difficult to
      characterize. As knowledge about endometriosis increases, classification schemes
      will change to incorporate new ideas. Evolution of the current American Fertility
      Society's revised classification of endometriosis is reviewed, as well as
      evaluation of its use with respect to prediction of fertility and management of
      pelvic pain. Possible directions for classification in the future are also
      discussed in this article.

PMID- 9163772
TI  - Modern medical management of endometriosis.
AB  - The modern medical management of endometriosis has changed considerably since the
      first attempts were made to control this disease hormonally over four decades
      ago. Currently, there are multiple choices for the clinician and patient,
      including oral contraceptives, danazol, GnRH agonist analogues, and gestrinone.
      Several advances have been made in the use of GnRH agonists in preventing some of
      the untoward effects of prolonged hypoestrogenism. These add-back regimens
      provide the best therapy available today for prolonged medical control of
      endometriotic symptoms. The antiprogesterones (RU-486) hold promise for the
      future, but are still in the investigational stage of development.

PMID- 9163773
TI  - Surgical treatment of endometriosis.
AB  - Surgical resection of endometriosis, previously possible only by means of
      laparotomy, can now be accomplished through laparoscopic techniques. The
      requirements for surgery, surgical principles, operative techniques, and results
      are summarized in this article, with emphasis on the laparoscopic approach.

PMID- 9163774
TI  - Extrapelvic endometriosis.
AB  - This article reviews extrapelvic endometriosis, emphasizing classic papers as
      well as recent research. Because of the nature of the existing literature,
      specifically case reports and retrospective analyses, this article is primarily
      descriptive in nature. Extrapelvic endometriosis is discussed based on some main
      areas of occurrence, including gastrointestinal, urinary, and thoracic; other
      areas are also reviewed. What is known about the epidemiology, pathogenesis,
      diagnosis, and treatment of extrapelvic endometriosis is highlighted. Areas for
      future direction of research in the field are also identified.

PMID- 9163775
TI  - Blaming the victim. The psychologizing of endometriosis.
AB  - When faced with a disease as baffling and mysterious as endometriosis, there may
      be a tendency to make up answers where there are none. Unfortunately, this has
      caused tremendous difficulties in studying the disease and has caused problems
      for patients. An examination of the way the disease has been psychologized sheds
      light on some of the confusion.

PMID- 9163776
TI  - The structure and future of endometriosis research.
AB  - Endometriosis is one of the most-investigated disorders of gynecology. Theories
      of various aspects of the disease are proposed but rarely are they adequately
      supported. This article examines several crucial areas in endometriosis
      investigation, with an eye toward recent developments. Critical evaluation of the
      quality of the tools is provided, and opinion on future directions is voiced.

PMID- 9163777
TI  - Pancreatic steatorrhea, malabsorption, and nutrition biochemistry: a comparison
      of Japanese, European, and American patients with chronic pancreatitis.
AB  - This article reports on steatorrhea, daily food intake, and fecal substances
      other than fecal fat (e.g., neutral sterols, bile acids, short-chain fatty acids)
      in pancreatic exocrine dysfunction arising from chronic pancreatitis (CP) in
      Japanese. European, and American patients. Changes in upper small intestinal pH
      and lipase secretion, plasma fatty acid profiles, serum fat-soluble vitamin
      levels and symptoms of their deficiency, and nutritional status are discussed in
      detail. Treatment of pancreatic steatorrhea is described. Throughout this study,
      we compared characteristics of maldigestion and malabsorption in these patient
      populations and our study revealed that fecal fat excretion reflected
      quantitative differences in fat consumption, plasma fatty acid profiles reflected
      quantitative and qualitative differences in fish oil consumption, and there were
      no differences in pancreatic exocrine dysfunction among these three groups. Since
      differences in fecal fat excretion and plasma fatty acid profiles appear to
      depend on dietary fats, the pathology and treatment of CP patients should be
      evaluated and the findings used to prescribe treatments.

PMID- 9163778
TI  - Does recurrent acute pancreatitis lead to chronic pancreatitis? Sequential
      morphological and biochemical studies.
AB  - The pathogenesis of chronic pancreatitis (CP) has been debated as to whether it
      is a de novo process or the consequence of acute pancreatitis (AP). We
      investigated whether recurrent AP in rats leads to CP, by sequential
      morphological and biochemical studies. Thirty male Wistar rats were fed a choline
      deficient diet with intraperitoneal ethionine injections twice daily at a dose of
      60 mg/100 g body weight twice weekly, and six rats were killed at 4, 6, and 8
      weeks; the remaining 12 rats, followed without further treatment, were killed at
      12 and 16 weeks. The pancreata from study and control groups were examined by
      histology, immunohistochemistry, and bio- and immunoassays. Histologically,
      moderate to severe intra- and perilobular fibrosis and other CP-like lesions
      appeared maximally at 8 weeks. Immunohistochemically, the earliest extracellular
      matrix change was strong fibronectin staining at 4 weeks, with a progressive
      increase to 8 weeks. Collagens I and III came to show strong, and collagen IV
      moderate, interstitial staining at 6-8 weeks. These morphological changes,
      however, returned to nearly normal at 16 weeks. Prolyl hydroxylase was
      significantly elevated at 4 and 6 weeks and normalized after 8 weeks, with no
      significant change in collagenase. In conclusion, our results suggest that even
      severe CP-like lesions induced by recurrent AP are reversible in the absence of
      persistently elevated prolyl hydroxylase and/or suppressed collagenase. The
      mechanism regulating these changes remains to be studied further.

PMID- 9163779
TI  - Glutathione synthesis in the exocrine pancreas.
AB  - Glutathione is essential for cellular cytoprotection, and in the exocrine
      pancreas, it is required for digestive enzyme synthesis. The purpose of these
      studies was to measure the capacity of the exocrine pancreas to synthesize
      glutathione, determine whether the pancreatic transsulfuration pathway has a role
      in providing cysteine needed for glutathione synthesis, and determine whether the
      glutathione synthetic capacity of the pancreas responds to pathologically
      relevant stresses. The activity of gamma-glutamylcysteine synthetase, the key
      regulatory enzyme for glutathione synthesis, was 3.56 +/- 0.29 mU/mg protein in
      the pancreas of fed rats, compared to 31 +/- 4 in the liver and 116 +/- 5 in the
      kidney. Studies using dispersed rat pancreatic acinar cells showed that the
      exocrine pancreas synthesizes glutathione from precursor amino acids and that the
      transsulfuration pathway is functionally intact in the pancreas and may serve as
      an important source of pancreatic cysteine. In mice, pancreatic gamma
      glutamylcysteine synthetase activity was induced 37% by corn oil, 77% by ethanol,
      and 88% by both treatments. Thus, the glutathione synthetic capacity of the
      pancreas is quantitatively less than that of the kidney or liver, but its key
      regulatory enzyme responds dynamically to pathologically relevant metabolic
      stresses, suggesting that glutathione is a key pancreatic cytoprotectant.

PMID- 9163780
TI  - In vivo assessment of lipid peroxidation in experimental edematous and
      necrotizing rat pancreatitis.
AB  - Lipid peroxidation, which may be involved in the pathogenesis of acute
      pancreatitis, is usually assessed in vitro or indirectly using antioxidants or
      free radical scavengers. We assessed lipid peroxidation in an in vivo model by
      measuring ethane exhalation in two models of acute pancreatitis. Edematous acute
      pancreatitis was induced by a supramaximal intraperitoneal injection of cerulein.
      Necrotizing acute pancreatitis was induced by retrograde infusion of sodium
      taurocholate into the pancreaticobiliary duct. Rats were placed in closed
      chambers and ethane exhalation was measured in aliquots. Ethane exhalation was
      significantly increased (p < 0.002) in cerulein (n = 12)- but not in taurocholate
      (n = 6)-induced pancreatitis compared to controls (n = 12 and 6, respectively).
      Our results suggest that free radicals may play a role in the pathogenesis of
      edematous pancreatitis but do not play an important role in the progression to
      necrotizing pancreatitis.

PMID- 9163782
TI  - Localization of glutamate receptor subunits of the alpha-amino-3-hydroxy-5-methyl
      4-isoxazolepropionate (AMPA) type in the pancreas of newborn guinea pigs.
AB  - Glutamate and related molecules are the major excitatory neurotransmitters in the
      central nervous system, and their receptors have been localized therein. Little
      is, however, known about them in the peripheral nervous system. The present study
      investigated the localization of glutamate receptor subunits of the alpha-amino-3
      hydroxy- 5-methyl-4-isoxazolepropionate (AMPA) type (GluR1, GluR2-3, and GluR4)
      in the pancreas of newborn guinea pigs. With a double-labeling method of
      immunofluorescence and immuno-tetrahydrochloride reaction, GluR1 and GluR4
      immunoreactivities were localized mostly in the insulin-secreting cells in the
      central mass of the islet, and GluR2-3 immunoreactivity in the peripheral rim of
      the islet, which consists mainly of non-insulin-secreting islet cells. With a
      double-labeling method employing immunofluorescence and NADPH-diaphorase (NADPH
      d) histochemistry, GluR2-3 and GluR4 immunoreactivities were localized in most of
      the NADPH-d positive pancreatic ganglion cells. None of the NADPH-d-positive
      ganglion cells showed GluR1 immunoreactivity. In fact, GluR1 immunoreactivity was
      not detected in any of the pancreatic ganglion cells. The results indicate that
      glutamate is likely to exert its effects on the pancreas by activating different
      AMPA receptor subunits located in endocrine cells and intrapancreatic ganglia.

PMID- 9163781
TI  - Oxidative stress changes in L-arginine-induced pancreatitis in rats.
AB  - The important role of oxygen radicals in acute experimental pancreatitis was
      demonstrated by study of the changes in the antioxidant system in the blood,
      liver, kidney, and pancreas of rats after the administration of a large quantity
      of L-arginine (L-Arg). The changes in lipid peroxidation and in reduced and
      oxidized glutathione were followed, as well as the activities of peroxide
      decomposing enzymes (glutathione peroxidase and catalase) and H2O2-producing
      superoxide dismutases. The results demonstrated that "oxidative stress" develops
      and acute pancreatitis appears rapidly after L-Arg treatment. Oxidative stress
      symptoms are expressed 24 h after the final treatment. Slow restitution of the
      studied antioxidant system can be demonstrated as early as after 48 h.

PMID- 9163783
TI  - Nitric oxide enhances endothelin production in pancreas transplantation.
AB  - The role of endothelin and its relationship with nitric oxide (NO) production in
      ischemia-reperfusion associated with pancreas transplantation has been explored.
      For this purpose, pancreatic levels of endothelin were evaluated in an
      experimental model of pancreas transplantation after different periods of cold
      preservation. The effects of NO synthase inhibition were also evaluated. Results
      show posttransplantation increases in lipase and endothelin production. The
      release of lipase and endothelin was only prevented by NG-nitro-L-arginine methyl
      ester after a short ischemic period. Thus, endothelin synthesis could be a
      consequence of stimulation with NO in the ischemia-reperfusion associated with
      pancreas transplantation.

PMID- 9163784
TI  - Morphological and immunocytochemical identification of periacinar fibroblast-like
      cells derived from human pancreatic acini.
AB  - Fibroblast-like cells in the periacinar region may play an important role in
      periacinar fibrosis. In the present study, we isolated and cultured periacinar
      fibroblast-like cells (PFCs) derived from human pancreatic acini and examined the
      characteristics of human PFCs morphologically and immunocytochemically.
      Immunocytochemical study of human PFCs showed that they were positively stained
      with antibodies against type I collagen/procollagen, type III
      collagen/procollagen, fibronectin, prolyl hydroxylase beta sub-unit, type IV
      collagen, laminin, alpha-smooth muscle actin, vimentin, and nonmuscle myosin.
      Electron microscopic study showed that human PFCs contained a number of
      microfilaments, forming dense bodies in the cytoplasm. These results indicated
      that human PFCs possess characteristics of myofibroblasts. Expression of alpha
      smooth muscle actin, a marker of the myofibroblast-like phenotype, was increased
      with time in culture and was enhanced by treatment with transforming growth
      factor (TGF)-beta 1. Collagen synthesis in human PFCs was stimulated by TGF-beta
      1 and the proliferation of human PFCs was stimulated by platelet-derived growth
      factor. These findings suggest that PFCs from human pancreas seem to be involved
      in periacinar fibrosis.

PMID- 9163785
TI  - Pancreatic secretory response to intrajejunal tryptophan: studies in dogs with an
      autotransplanted entire jejunoileum.
AB  - In two sets of dogs with gastric, duodenal, and jejunal fistulas, we studied the
      effect of atropine (14 nmol/ kg/h) on the pancreatic secretory response to
      intrajejunal tryptophan (0.12-10.0 mmol/h; given against a secretin background)
      before (n = 7) and after extrinsic denervation of the jejunoileum (orthotopical
      autotransplantation; n = 6). Plasma levels of cholecystokinin were determined by
      radioimmunoassay. The incremental bicarbonate response to tryptophan was not
      significantly different between the two sets of dogs. Atropine had no effect on
      the incremental bicarbonate response to tryptophan. In both sets of dogs,
      intrajejunal tryptophan caused a dose-dependent increase in pancreatic protein
      output, which was reduced by atropine. The tryptophan-stimulated levels of plasma
      cholecystokinin were not significantly altered by denervation and or atropine. We
      conclude that in dogs (1) intrajejunal tryptophan stimulates pancreatic
      bicarbonate and protein secretion via release of hormones, (2) extrinsic
      denervation of the jejunoileum does not significantly alter the incremental
      bicarbonate and protein responses to intrajejunal tryptophan, (3) the cholinergic
      intrinsic nerves of the jejunoileum and the hormone cholecystokinin are probably
      involved in control of the pancreatic protein response to tryptophan, and (4) the
      release of cholecystokinin by intrajejunal tryptophan does not depend on the
      extrinsic and intrinsic cholinergic nerves of the jejunoileum.

PMID- 9163786
TI  - Retardation of pancreatic regeneration after partial pancreatectomy in a strain
      of rats without CCK-A receptor gene expression.
AB  - This study extends a recent observation that Otsuka Long-Evans Tokushima Fatty
      (OLETF) rats show no expression of the cholecystokinin (CCK)-A receptor gene in
      the pancreas because of a genetic abnormality. We compared the changes in
      pancreatic regeneration in terms of wet weight and protein and DNA contents after
      partial pancreatectomy (30% resection) in OLETF and control (Long-Evans Tokushima
      Otsuka: LETO) rats and examined whether the CCK-B receptor has a role in
      pancreatic regeneration after pancreatectomy. The pancreatic wet weight increased
      significantly with age in both OLETF and LETO rats regardless of surgical
      procedure, but the increase with respect to time was significantly less in OLETF
      than in LETO rats. The protein and DNA concentrations in the pancreas (mg/g wet
      tissue) were comparable for both strains after sham operation. However, they were
      significantly lower than pancreatectomy in OLETF rats compared to those after
      sham operation, whereas they were comparable in LETO rats regardless of surgical
      procedure. The ratio of protein content/DNA content (cell size) was significantly
      lower in OLETF than LETO rats under all conditions. CCK-B receptor gene
      expression was not enhanced after pancreatectomy. In conclusion, the CCK-A
      receptor is not an absolute requirement for pancreatic normal growth but is
      important for pancreatic regeneration.

PMID- 9163787
TI  - A simple method for purification of adult pig pancreatic endocrine cells.
AB  - Adult pig pancreatic endocrine cells were harvested by autodigestion without
      added enzymes. The isolated, crude cells were purified by mono-poly resolving
      medium (MPRM). The purity of the harvested cells was determined by dithizone
      staining and the number of pancreatic endocrine cells was counted. A large number
      of the cells were stained red with dithizone and showed a high viability and a
      good insulin secretory response to glucose stimulation. The average number of
      cells purified by MPRM was 3.40 +/- 1.32 x 10(5) cells/g pancreas and the number
      of dithizone-stained cells was 2.81 +/- 1.09 x 10(5) cells/g pancreas. The
      insulin secretion from the pancreatic endocrine cells was maintained throughout a
      40-day observation period and high glucose stimulation induced an increase in
      insulin secretion from the cultured cells. In the cells purified by MPRM, light
      and electron microscopic studies showed the cells to be typical pancreatic
      endocrine cells. The present purification method using MPRM allowed us quickly to
      obtain a large amount of adult pig pancreatic endocrine cells from the unpurified
      preparations. It is thought to be useful for transplantation and biochemical or
      biological studies of adult pig pancreatic endocrine cells.

PMID- 9163788
TI  - Embryological fusion between the ducts of the ventral and dorsal primordia of the
      pancreas occurs in two manners.
AB  - The junction between the main pancreatic duct and the accessory duct has been
      thought to be the site of fusion between the ducts of the ventral and the dorsal
      primordia of the pancreas. The aim of this study was to investigate the fusion
      point between the ventral and the dorsal pancreatic ducts and to determine
      whether there is any relationship between the configuration of the pancreatic
      ducts and the manner of embryological fusion. Pancreatography was performed at 22
      consecutive autopsies. Immunohistochemical staining of pancreatic polypeptide
      (PP) was performed because PP cells were rich in the ventral pancreas but poor in
      the dorsal pancreas. We identified two types of fusion. In one type, the ventral
      and the dorsal pancreatic ducts fuse at their junction (one-point fusion). In the
      other type, the two ducts fuse not only at the proximal site but at a second,
      more distal site (two-point fusion). Analysis of the pancreatograms showed that
      the distance between the junction and the major papilla in two-point fusion is
      significantly shorter than in one-point fusion (p < 0.01). These results indicate
      a close correlation between the pattern seen on pancreatograms and the manner of
      embryological fusion.

PMID- 9163789
TI  - Complete regression of the ventral pancreatic duct as a cause for recurrent acute
      pancreatitis: demonstration by MR cholangiopancreatography.

PMID- 9163790
TI  - Dialyzing the elderly: benefit or burden?

PMID- 9163791
TI  - Detrimental effects of peritoneal dialysis solutions upon in vivo and in situ
      exposed mesothelium.

PMID- 9163792
TI  - Impact of different dialysis solutions on solute and water transport.

PMID- 9163793
TI  - Advanced glycosylation end products in peritoneal tissue with different
      solutions.

PMID- 9163794
TI  - Plasticizers in renal failure: aspects of metabolism and toxicity.

PMID- 9163795
TI  - Evidence for the presence of chronic inflammation during peritoneal dialysis:
      therapeutic implications.

PMID- 9163796
TI  - Peritoneal dialysis solution biocompatibility: inhibitory mechanisms and recent
      studies with bicarbonate-buffered solutions.

PMID- 9163797
TI  - Polyglucose solutions in CAPD.

PMID- 9163798
TI  - Bicarbonate-buffered CAPD solutions: from clinical trials to clinical practice.

PMID- 9163799
TI  - Further animal and human experience with a 0.6% amino acid/1.4% glycerol
      peritoneal dialysis solution.

PMID- 9163800
TI  - Polyglucose and amino acids: preliminary results.

PMID- 9163801
TI  - Icodextrin plus glucose combinations for use in CAPD.

PMID- 9163802
TI  - Future clinical research with icodextrin-containing solutions.
AB  - Icodextrin-based solutions have been investigated for over ten years and are
      commercially available in some countries in Europe. Although many studies have
      been described using icodextrin, we believe that there are many interesting areas
      remaining for clinical research with icodextrin-based PD solutions. Included in
      these are the careful examination of the kinetics of icodextrin during the 14-16
      hour daytime exchange in CCPD, new studies investigating fluid absorption during
      icodextrin exchanges, and finally, the potential use of icodextrin in an early
      start dialysis regime. We look forward to seeing the results from these very
      interesting studies.

PMID- 9163803
TI  - Oligopeptides as osmotic agents for peritoneal dialysis.

PMID- 9163804
TI  - N-acetylglucosamine: a new osmotic solute in peritoneal dialysis solutions.

PMID- 9163805
TI  - Erythropoietin 1997: a brief update.

PMID- 9163806
TI  - The peritoneal dialysis system: importance of each component.

PMID- 9163807
TI  - Factors affecting peritoneal efficiency in different treatment schedules.

PMID- 9163808
TI  - The impact of residual renal function on the adequacy of peritoneal dialysis.

PMID- 9163809
TI  - The CANUSA study. Canada-USA.

PMID- 9163810
TI  - Long-term outcomes of peritoneal dialysis.

PMID- 9163811
TI  - Applications in kinetic modeling using PD ADEQUEST.

PMID- 9163812
TI  - PACK PD: a urea kinetic modeling computer program for peritoneal dialysis.

PMID- 9163813
TI  - Personal dialysis capacity.

PMID- 9163814
TI  - From origin to ISPD home page: a discourse on the Internet.

PMID- 9163815
TI  - The use of the Internet.

PMID- 9163816
TI  - Silver-coated catheters in peritoneal dialysis.

PMID- 9163817
TI  - The Cruz catheter and its functional characteristics.

PMID- 9163818
TI  - Peritoneal dialysis is a real clinical option.

PMID- 9163819
TI  - Integration of peritoneal dialysis in active uremia treatment.

PMID- 9163820
TI  - The referral pattern of patients with ESRD is a determinant in the choice of
      dialysis modality.

PMID- 9163821
TI  - The crucial role of medical and nursing staff in the care of chronic peritoneal
      dialysis patients.

PMID- 9163822
TI  - Integration of peritoneal dialysis and transplantation programs.

PMID- 9163823
TI  - Flightlessness and phylogeny amongst endemic rails (Aves:Rallidae) of the New
      Zealand region.
AB  - The phylogenetic relationships of a number of flightless and volant rails have
      been investigated using mtDNA sequence data. The third domain of the small
      ribosomal subunit (12S) has been sequenced for 22 taxa, and part of the 5' end of
      the cytochrome-b gene has been sequenced for 12 taxa. Additional sequences were
      obtained from outgroup taxa, two species of jacana, sarus crane, spur-winged
      plover and kagu. Extinct rails were investigated using DNA extracted from
      subfossil bones, and in cases where fresh material could not be obtained from
      other extant taxa, feathers and museum skins were used as sources of DNA.
      Phylogenetic trees produced from these data have topologies that are, in general,
      consistent with data from DNA-DNA hybridization studies and recent
      interpretations based on morphology. Gallinula chloropus moorhen) groups basally
      with Fulica (coots), Amaurornis (= Megacrex) ineptus falls within the
      Gallirallus/Rallus group, and Gallinula (= Porphyrula) martinica is basal to
      Porphyrio (swamphens) and should probably be placed in that genus. Subspecies of
      Porphyrio porphyrio are paraphyletic with respect to Porphyrio mantelli (takahe).
      The Northern Hemisphere Rallus aquaticus is basal to the south-western Pacific
      Rallus (or Gallirallus) group. The flightless Rallus philippensis dieffenbachii
      is close to Rallus modestus and distinct from the volant Rallus philippensis, and
      is evidently a separate species. Porzana (crakes) appears to be more closely
      associated with Porphyrio than Rallus. Deep relationships among the rails remain
      poorly resolved. Rhynochetus jubatus (kagu) is closer to the cranes than the
      rails in this analysis. Genetic distances between flightless rails and their
      volant counterparts varied considerably with observed 12S sequence distances,
      ranging from 0.3% (Porphyrio porphyrio melanotus and P. mantelli mantelli) to
      7.6% (Rallus modestus and Rallus philippensis). This may be taken as an
      indication of the rapidity with which flightlessness can evolve, and of the
      persistence of flightless taxa. Genetic data supported the notion that flightless
      taxa were independently derived, sometimes from similar colonizing ancestors. The
      morphology of flightless rails is apparently frequently dominated by evolutionary
      parallelism although similarity of external appearance is not an indication of
      the extent of genetic divergence. In some cases taxa that are genetically close
      are morphologically distinct from one another (e.g. Rallus (philippensis)
      dieffenbachii and R. modestus), whilst some morphologically similar taxa are
      evidently independently derived (e.g. Porphyio mantelli hochstetteri and P.m.
      mantelli).

PMID- 9163824
TI  - Design strategies of sea urchin teeth: structure, composition and micromechanical
      relations to function.
AB  - The teeth of sea urchins comprise a variety of different structural entities, all
      of which are composed of magnesium-bearing calcite together with a small amount
      of organic material. The teeth are worn down continuously, but in such a way that
      they remain sharp and functional. Here we describe aspects of the structural,
      compositional and micromechanical properties of the teeth of Paracentrotus
      lividus using scanning electron microscopy, infrared spectrometry, atomic
      absorption. X-ray diffraction and microindentation. The S-shaped single
      crystalline calcitic fibres are one of the main structural elements of the tooth.
      They extend from the stone part to the keel. The diameter of the fibres increases
      gradually from less than 1 micron at the stone tip to about 20 microns at the
      keel end, while their MgCO3 contents decrease from about 13 mol% to about 4.5
      mol%. Each fibre is coated by a thin organic sheath and surrounded by
      polycrystalline calcitic discs containing as much as 35 mol% MgCO3. This
      structure constitutes a unique kind of gradient fibre-reinforced ceramic matrix
      composite, whose microhardness and toughness decrease gradually from the stone
      part to the keel. Primary plates are also important structural elements of the
      tooth. Each primary plate has a very unusual sandwich-like structure with a
      calcitic envelope surrounding a thin apparently amorphous CaCO3 layer. This
      central layer, together with the primary plate/disc interface, improves the
      toughness of this zone by stopping and blunting cracks. The self-sharpening
      function of the teeth is believed to result from the combination of the
      geometrical shape of the main structural elements and their spatial arrangement,
      the interfacial strength between structural elements, and the hardness gradient
      extending from the working stone part to the surrounding zones. The sea urchin
      tooth structure possesses an array of interesting functional design features,
      some of which may possibly be applicable to materials science.

PMID- 9163825
TI  - Correlated evolution and independent contrasts.
AB  - The use of the independent contrast method in comparative tests is studied. It is
      assumed that: (i) the traits under investigation are subject to natural
      selection; (ii) closely related species are similar because they share many
      characteristics of their niche, inherited from a common ancestor; and (iii) the
      current adaptive significance of the traits is the focus of investigation. The
      main objection to the use of species values in this case is that third variables
      which are shared by closely related species confound the relationship between the
      focal traits. In this paper, I argue that third variables are largely not
      controlled by the contrast methods, which are designed to estimate correlated
      evolution. To the extent that third variables also show correlated evolution, the
      true relationship among the traits of interest will remain obscured. Although the
      independent contrast method does not resolve the influence of third traits it
      does, in principle, provide a greater resolution than the use of the species mean
      values. However, its validity depends on the applicability of an evolutionary
      model which has a substantial stochastic component. To illustrate the
      consequences of relaxing this assumption I consider an alternative model of an
      adaptive radiation, where species come to fill a fixed niche space. Under this
      model, the expected value for the contrast correlation differs from that for the
      species correlation. The two correlations differ because contrasts reflect the
      historical pattern of diversification among species, whereas the species values
      describe the present-day relationships among the species. If the latter is of
      interest, I suggest that assessing significance based on the species correlations
      can be justified, providing that attention is paid to the role of potentially
      confounding third traits. Often, differences between contrast and species
      correlations may be biologically informative, reflecting changes in correlations
      between traits as an adaptive radiation proceeds; contrasts may be particularly
      useful as a means of investigating past history, rather than current utility of
      traits.

PMID- 9163826
TI  - The diagnosis and management of small (< or = 3 cm) renal neoplasms: a
      commentary.
AB  - Many renal cell carcinomas are discovered incidentally. This phenomenon is
      largely attributable to advances in renal imaging, particularly regarding CT, to
      the widespread use of cross-sectional imaging in the diagnosis of abdominal
      disease, and to growing experience with the detection and diagnosis of renal
      masses. Accompanying the apparent increasing prevalence of renal masses are
      several controversies that specifically concern small (< or = 3 cm) neoplasms,
      those that are of a size associated with relatively slow growth and a low risk of
      metastasis. Are some of these small neoplasms renal adenomas? What is their
      growth pattern, and of what significance is their enlargement? Are all small
      renal carcinomas truly "cancers"? And what are the implications for management of
      such lesions in an asymptomatic individual? These controversies are discussed in
      depth in the hope of stimulating further investigation of this complex problem.

PMID- 9163827
TI  - Helical CT for detection and characterization of renal masses.
AB  - Helical CT permits the radiologist to image the kidney continuously, eliminating
      the chances of scanner misregistration. In addition, the kidneys can now be
      imaged during essentially any phase of contrast material enhancement. Although
      this offers greater flexibility to the imager, a number of potential problems
      with helical CT must be considered, particularly when it is performed during the
      cortical phase of renal enhancement. This article reviews both the advantages and
      potential pitfalls of helical CT when used for both detection and
      characterization of renal masses.

PMID- 9163828
TI  - The role of imaging in staging renal adenocarcinoma.
AB  - Numerous surgical options are available to physicians treating patients with
      renal adenocarcinoma. In the current clinical setting, imaging plays a key role
      in determining which options are selected. Newer imaging techniques such as
      helical CT with CT angiography, MRI, and ultrasound (US) have improved staging
      capabilities in this patient population. However, to approach staging accuracies
      recently reported, attention must be paid to proper imaging parameters. This
      article describes the strengths, limitations, and proper techniques used for
      staging renal adenocarcinoma with CT, MRI, and US.

PMID- 9163829
TI  - Imaging of angiomyolipomas.
AB  - In this article we review renal angiomyolipomas (AMLs) from cases in the world
      literature and 60 cases from our own institution. We also analyze the role and
      the place of the various imaging techniques in the detection and diagnosis of
      AMLs. Discussion is focused on the natural history of this benign neoplasm as an
      isolated form or as a part of the tuberous sclerosis (TS) complex or as part of a
      third less certain group of multiple AML without stigmata of TS. We also consider
      the growth patterns and hemorrhagic risks of AML to help define an approach to
      the current management of this lesion.

PMID- 9163830
TI  - Computed tomography of renal metastases.
AB  - Since the advent of CT, secondary neoplastic lesions of the kidneys have been
      detected with increasing frequency. After reviewing a large series of cases of
      renal metastases, we have been able to classify the CT findings into seven major
      categories that are discussed and illustrated in this article. The differential
      diagnoses between metastatic disease of the kidneys and other lesions such as
      renal infarctions, renal lymphoma, and primary malignancies are also considered.

PMID- 9163831
TI  - Delayed CT in acute renal infection.
AB  - CT scans of the kidneys obtained approximately 3 hours after contrast
      administration often reveal useful information in patients with renal infections.
      In this article, we discuss three main features of these delayed scans. Feature 1
      shows a nephrogram replacing a variable portion of the low density areas present
      in the early enhanced phase. The nephrogram can be streaky, band-like, cone or
      horseshoe-shaped; Feature 2 exhibits a focal staining or a hyperdense rim
      surrounding microabscesses and macroabscesses; Feature 3, very rare, is
      characterized by hyperdense areas located far from the lesions detected on early
      scans. These features make it possible to better define the actual extent of
      infection and the presence of the edema, improving diagnostic confidence.

PMID- 9163832
TI  - MRI and CT in blunt renal trauma: an update.
AB  - In our experience, MRI is as effective as CT in correctly staging renal injury.
      The coronal and sagittal slice orientations of MRI are particularly helpful in
      determining the extent of the renal parenchymal damage. Both methods are accurate
      in finding perirenal hematomas, assessing the viability of renal fragments, and
      detecting preexisting renal abnormalities but are relatively inaccurate in
      visualizing urinary extravasation. Although CT remains the method of choice in
      radiological staging of renal injury, MRI can complement CT in patients with
      severe renal injury, preexisting renal abnormality, equivocal CT findings, or
      when repeated radiological follow-up is required. MRI could replace CT in
      patients with iodine allergy and be used for initial staging if CT is not
      available.

PMID- 9163833
TI  - Renovascular disease: Doppler ultrasound.
AB  - Color Doppler ultrasound (CDUS) seems to be an effective imaging technique for
      the diagnosis of renal vascular diseases. It is already the modality of choice
      for the detection of acute renal vein thrombosis and nonocclusive intrarenal
      vascular disorders including iatrogenic arteriovenous fistula and false aneurysm,
      particularly in patients with impaired renal function that precludes the use of
      iodinated contrast agents. Although proximal Doppler interrogation remains an
      important step in diagnosing renal artery (RA) stenosis, useful hemodynamic
      information can be obtained from the distal arterial bed. When CDUS fails in
      identifying proximal RAs, normal waveform velocity and morphology obtained from
      intrarenal arteries enable one to rule out RA occlusion and most of the severe
      stenoses (> or = 80%). Such information, which is not subject to a significant
      risk of technical failure, seems to be particularly useful in studying patients
      with acute renal failure of suspected vascular origin. Despite the extreme
      variability in reported performance between studies, CDUS has seemed to be a
      valuable tool compared with other noninvasive modalities in the diagnosis of RA
      stenosis. Whereas a CDUS-based strategy is already accepted in numerous
      specialized centers, a thorough evaluation of diagnostic criteria and extensive
      training of operators will allow CDUS to be widely accepted for the screening of
      patients at high risk for renovascular hypertension.

PMID- 9163834
TI  - Duplex Doppler evaluation of acute renal obstruction.
AB  - Patients with possible acute renal obstruction often undergo numerous types of
      radiological examinations. Renal Doppler ultrasound is a quick and noninvasive
      way to assess for physiological and hemodynamic changes that accompany acute
      obstruction. The renal Doppler study may provide unique data not available from
      conventional sonography. Most, but not all, clinical and laboratory studies
      regarding Doppler of acute renal obstruction have reported encouraging results.
      As limitations to the Doppler examination in this clinical setting are
      delineated, a proper role for renal Doppler will continue to emerge.

PMID- 9163835
TI  - Glaucoma associated with uveitis.
AB  - Raised intraocular pressure is a common and frequently serious complication of
      anterior uveitis. The milieu of inflammatory cells, the mediators they release,
      and the corticosteroid therapy used to treat the uveitis can participate in the
      pathogenesis of uveitic glaucoma. These factors alter the normal anatomic
      structure of the anterior chamber and angle, influencing aqueous production and
      outflow. These changes act to disrupt the homeostatic mechanisms of intraocular
      pressure control. Structural changes in the angle can be acute, such as in
      secondary angle closure with pupillary block glaucoma, or chronic, such as
      combined steroid-induced and secondary open angle glaucoma. Management of uveitic
      glaucoma may be difficult because of the numerous mechanisms involved in its
      pathogenesis. Diagnostic and therapeutic decisions are guided by careful
      delineation of the pathophysiology of each individual case. The goal of treatment
      is to minimize permanent structural alteration of aqueous outflow and to prevent
      damage to the optic nerve head. This article reviews the pathogenesis of uveitic
      glaucoma, with specific attention to etiology. Medical and surgical therapies are
      also discussed, with emphasis on the more recent developments in each category.

PMID- 9163836
TI  - Antibiotic selection in the treatment of endophthalmitis: the significance of
      drug combinations and synergy.
AB  - Emerging resistance of organisms to standard antibiotic therapy has forced
      clinicians to continually evaluate the best intraocular antibiotics for the
      treatment of endophthalmitis. Early diagnosis and appropriate treatment with
      intraocular antibiotics are important factors in the successful management of
      endophthalmitis. Although drug combinations are necessary to cover the full range
      of bacteria causing endophthalmitis, antimicrobial synergy is probably less
      important in endophthalmitis treatment because of the high intravitreal
      concentration of individual antibiotics achieved by intravitreal injection. In
      the treatment of bacterial endophthalmitis, the combination of intravitreal
      vancomycin (1 mg/0.1 cc) and ceftazidime (2.25 mg/ 0.1 cc) is a reasonable
      alternative to the combination vancomycin and amikacin (0.4 mg/ 0.1 cc).

PMID- 9163837
TI  - Acute loss of vision during pregnancy due to a suprasellar mass.
AB  - A pregnant woman presented with headaches, bilateral decreased visual acuity, and
      a central scotoma with a superotemporal hemianopic defect in the right eye and a
      superotemporal hemianopic defect in the left eye, and bilateral temporal optic
      disk pallor. Neuroimaging revealed an intrasellar mass with suprasellar
      extension. Biopsy of the lesion revealed lymphocytic hypophysitis (LH). Treatment
      with steroids produced marked improvement in visual function. The clinical
      presentation of lymphocytic hypothysitis may mimic pituitary adenoma and the
      diagnosis should be suspected in any pregnant or postpartum patient with an
      intrasellar or suprasellar mass.

PMID- 9163839
TI  - Recurrent hyphema secondary to anterior chamber lens implant.
AB  - Ultrasound biomicroscopy, a high frequency ultrasound imaging device, allows high
      resolution images of the anterior segment. We report a case of recurrent hyphema
      secondary to anterior chamber lens implant. Corneal edema precluded visualization
      of the angle and lens haptic, and B-scan ultrasound provided no information about
      the lens implant. In contrast, ultrasound biomicroscopy precisely located the
      superior haptic and revealed that it was deeply embedded within the ciliary body.

PMID- 9163838
TI  - Infection of the conjunctiva by Rhinosporidium seeberi.
AB  - Rhinosporidiosis is an unusual fungal disease that rarely affects the eye. It was
      first described as a pathogen in humans at the turn of the century. The etiologic
      agent, Rhinosporidium seeberi, commonly produces granulomatous inflammation of
      the upper respiratory mucosa. Most reported ocular infections have occurred in
      hot, dry climatic regions. We present a case of conjunctival rhinosporidiosis in
      an 11-year-old boy from western New York state, the first such report from the
      temperate zones of North America. The clinical characteristics, histopathologic
      features, and recommended therapeutic measures are discussed.

PMID- 9163840
TI  - Rubens Peale's spectacles: an optical illusion?
AB  - The painting Rubens Peale with a Geranium (1801), by Rembrandt Peale, has earned
      a reputation as a masterpiece of early American portraiture. In recent years the
      painting has also been the source of controversy, because Rubens was depicted
      with two pairs of eyeglasses at a time when most people would not have been
      portrayed with spectacles at all. Scholars of American art history and
      ophthalmology have studied the painting and have promoted various theories for
      this peculiarity. A combined study of the painting, historical documentation, and
      optical effects in the painting, however, sheds new light on the answer to this
      mystery.

PMID- 9163841
TI  - Homocystinuria and Marfan's syndrome.

PMID- 9163842
TI  - Nutritional evaluation of women in urban and rural areas in Korea as studied by
      total food duplicate method.
AB  - Nutrient intake was studied by the total food duplicate method in 141 adult
      working women (at the ages of 21 to 56 years) in four regions (Seoul, Pusan,
      Chunan and Haman) in Korea. Clinical, hematological and anthropometrical
      examinations were conducted in parallel. The nutrient intakes were estimated in
      reference to the weight of each food item and the national standard food
      composition tables for Korean population, and evaluated in comparison with the
      nationally recommended dietary allowances (RDA). The intakes were essentially
      sufficient when evaluated on a group basis. Plant-based foods were major sources
      of both protein (67%) and lipid (72%). Dinner was the most substantial sources of
      all nutrients. Further evaluation on an individual basis taking 80-120% RDA as
      acceptable showed that young people (at the ages of 20-29 years) and those in
      Seoul had highest prevalence of insufficient intake of nutrients, especially
      energy, protein and iron. Consumption of rice, the traditional staple food, was
      the lowest in Seoul and in the youngest groups as compared with others. The
      prevalence of overweight cases was also the lowest in the Seoul participants. The
      two observations when combined apparently suggest the difficulties in public
      nutrition.

PMID- 9163843
TI  - Quantitative and qualitative characteristics of frozen-thawed bovine spermatozoa
      recovered via a conventional and a standardized swim-up technique.
AB  - The objective of this study was to use the bovine as a model to evaluate the
      recovery of frozen-thawed spermatozoa via a conventional and a standardized swim
      up technique. Frozen-thawed semen specimens (3 bulls) were washed and
      reconstituted with 2.9% (w/v) sodium citrate extender containing 20% (v/v)
      chicken egg yolk (SC-EY). Reconstituted sperm specimens were used for selection
      via conventional swim-up and the standardized ZSC method. The swim-up method
      consisted of overlayering the sperm specimen with 0.7 to 1.0 ml of isolation
      media (Ham's F-10), followed by 1 hr of incubation. The ZSC consisted of a
      conical cavity on the bottom of a glass column. The sperm specimen was placed
      into the conical cavity until the surface of the specimen was at the same level
      as the upper boundaries of the conical cavity. The surrounding periconical and
      epiconical areas were filled with 0.7 to 1.0 ml of isolation media followed by 1
      hr of incubation. The isolation media was removed (harvesting) from swim-up (80%
      volume) and ZSC specimens (100% volume) at the end of incubation. Recovered
      specimens were assessed for volume (ml), sperm concentration (x10(6)
      spermatozoa/ml), the percentage and grade of motility (0 to 4), the occurrence of
      osmotic shock and the percentage of spermatozoa reactive to the hypoosmotic
      swelling (HOS) test. Swim-up and ZSC selected specimens were qualitatively
      similar to each other. However, higher numbers of spermatozoa were recovered when
      sperm specimens were processed via the ZSC method (1.6 fold increase) than with
      the conventional swim-up technique. Because the ZSC method enabled the recovery
      of up to 100% of the overlayered media, it also enabled the recovery of most of
      the spermatozoa that migrated from the sperm specimen into the isolation media
      with no possibility of mixing the two, which was the case with the swim-up
      method, and which could also contaminate the recovered specimen with dead and
      immotile spermatozoa. Thus, the ZSC technique enabled the harvesting of the
      medium closest to the underlayered sperm specimen, which contributed to maximize
      the number of sperm recovered. When all assessed parameters were noted and all
      clinical improvements and efficiency of the method were compared to the swim-up
      technique, the sperm manipulation procedure of choice was clearly the ZSC method.

PMID- 9163844
TI  - Incidence of hepatocellular carcinoma after interferon therapy in patients with
      chronic hepatitis C.
AB  - We examined the effect of interferon (IFN) therapy for chronic active hepatitis
      (CAH) C in 207 patients by estimating the incidence of hepatocellular carcinoma
      (HCC) after IFN therapy using the person-years method. Statistical analysis was
      performed using the Mantel-Haenszel chi-square test. No HCC was detected in
      patients with normal serum alanine aminotransferase (ALT) levels after IFN
      therapy (response-effect group), and in patients with both normal serum ALT
      levels and hepatitis C virus (HCV)-RNA clearance after IFN therapy (complete
      responder group). The incidence per 100,000 person-years in the patients with
      elevated serum ALT level after IFN therapy (other-effects group) were 1968 and
      1624, respectively. The incidence in control patients who did not achieve IFN
      therapy was 901. No statistically significant differences were observed between
      the other-effects group, non-responder group, and the control group. Our results
      so far suggest that normalization of the serum ALT levels and/or HCV clearance
      might reduce the incidence of HCC.

PMID- 9163845
TI  - Significance of elevated procollagen-III-peptide and transforming growth factor
      beta levels of bronchoalveolar lavage fluids from idiopathic pulmonary fibrosis
      patients.
AB  - Although both procollagen III aminopeptide (P-III-P) and transforming growth
      factor-beta (TGF-beta) are reported to be present in lung tissue and/or elevated
      in bronchoalveolar lavage fluid (BALF) from idiopathic pulmonary fibrosis (IPF)
      patients, we have little knowledge concerning the clinical significance of
      elevated P-III-P and TGF-beta levels in BALF. Using a radioimmunoassay, we
      measured P-III-P and TGF-beta in BALF from 48 IPF patients (16F and 32M, 59 +/- 2
      years, mean +/- S.E.) who received BAL in our clinic over the past 13 years
      before glucocorticosteroid treatment. Among them, we could detect a significant
      amount of P-III-P (2.2 +/- 1.0 U/ml; range 0.03 to 16.5 U/ml) in BALF in 18 of
      the patients (5F and 13M, 58 +/- 3 years) (group B). but not (0.03 U/ml or less)
      in the other 30 patients (11F and 19M, 59 +/- 2 years) (group A). Lymphocyte (%)
      and basophil (%) in BALF from group B was much larger than that from group A (33%
      vs. 8%, p < 0.01). Group B showed a longer duration of onset to BAL (36 months
      vs. 23 months, p < 0.05). TGF-beta levels were obtained using an ELISA system kit
      from the same BALF samples. TGF-beta was not detected in 10 patients (100 pg/ml
      or less) (3F and 7M, 59 +/- 4 years) (group I), while the remaining 38 patients
      showed a significant amount of TGF-beta (329 +/- 44 pg/ml, range 100 to 1,360
      pg/ml). The latter patients were further divided into two groups; group II 100 to
      300 pg/ml (10F and 14M, 56 +/- 3 years) and group III 350 or more (3F and 11M, 63
      +/- 2 years). Group III showed significantly better values in PaO2, Aa-DO2, %VC
      and %DLco, and smaller percentage of basophils in BALF than did groups I and/or
      II, whereas survival after BAL in group III was significantly shorter than in
      group I (31 vs. 19 months, p < 0.05). There was no significant relationship
      between P-III-P and TGF-beta levels in BALF. These findings suggest that elevated
      P-III-P level is accompanied by an increase in lymphocyte population in BALF from
      IPF patients, resulting in a longer duration of the disease, while elevated TGF
      beta level reflects alveolar inflammation at an earlier stage of the disease
      which induces a progression of the disease, resulting in a shorter survival in
      IPF patients.

PMID- 9163846
TI  - Effect of sex hormones on the tissue localization of nuclear estrogen receptor
      positively stained cells in the seminal vesicle of immature castrated rats.
AB  - We studied the changes in the tissue localization of nuclear estrogen receptor
      (ER) positively stained cells in the seminal vesicle of immature castrated rats
      under various environmental conditions of sex hormones by immunohistochemical
      methods. In castrated rats of 6 weeks of age, the percentage of nuclear ER
      positively stained cells showed remarkable increase in the periglandular stroma
      region, but not in the epithelium and the peripheral stroma region. Estrogen
      administration to castrated rats dramatically increased the percentage of nuclear
      ER positively stained cells in both the epithelium and the peripheral stroma
      region, whereas cessation of estrogen treatment caused a significant percentile
      decrease. These results suggest that the nuclear ER expression in both the
      epithelial cells and the peripheral stromal cells seems to respond to estrogen.
      The concomitant treatment of estradiol-17 beta (E2) with 5 alpha
      dihydrotestosterone (DHT) completely inhibited these E2 mediated ER expression in
      the epithelium and the stroma. This result suggests that ER works only when E2 is
      given in the absence of DHT in the seminal vesicle of immature castrated rats.

PMID- 9163847
TI  - Wavelength dependency of photoparoxysmal responses in photosensitive nonepileptic
      subjects.
AB  - Using specially made optical filters, we analyzed the wavelength dependency of
      photoparoxysmal responses (PPRs) in five photosensitive nonepileptic subjects.
      The wavelength spectrum around 700 nm (680-700 nm) was estimated as the only
      visible spectrum essential for eliciting PPRs in two normal trichromat
      nonepileptic subjects, although the effect of some wavelength spectra (360-400 nm
      and 520-580 nm) was uncertain. The wavelength dependency of PPRs in two
      photosensitive nonepileptic subjects was the same as that found in some patients
      with photosensitive idiopathic generalized epilepsy.

PMID- 9163848
TI  - Abnormal lipid metabolism and renal disorders.
AB  - Abnormal renal diseases including nephrotic syndrome and chronic renal failure
      are associated with hyperlipidemia, significance of abnormal lipid metabolism has
      been thought to be limited in some inherited renal diseases. However, recent
      studies have postulated that glomerulosclerosis is induced by hyperlipidemia and
      is in common with atherosclerosis. This involvement is found in the progressive
      renal disorders, e.g., focal glomerular sclerosis, diabetic nephropathy and
      glycogen storage disease. Interaction between macrophages and mesangial cells may
      play an important role in such conditions. This evidence is supported by
      experimental models with hyperlipidemia. On the other hand, discovery and new
      hereditary metabolic disorders, such as type III hyperlipoproteinemia and
      lipoprotein glomerulopathy, shows that apolipoprotein (apo) E abnormalities are
      responsible for the glomerular lesions. Especially, lipoprotein glomerulopathy
      has specific features different from those of lipid-induced renal diseases. In
      this disease, apo E Sendai which results from new substitution (Arginine 145-
      >Proline) may induce intraglomerular lipoprotein thrombi characteristic of
      lipoprotein glomerulopathy.

PMID- 9163849
TI  - Nutritional evaluation of Chinese working women in the city of Tainan, Taiwan.
AB  - Nutritional survey was conducted in 1994 in Tainan City, southern Taiwan. Total
      food duplicate samples were collected from 52 women volunteers. Clinical
      examinations, anthropometry, hematology and serum biochemistry were also
      conducted. The intakes of nutrients were estimated from the weights of food items
      in reference to the standard food composition tables for Taiwanese. On average,
      the participants took 1,973 kcal energy, 69 g protein, 73 g lipid and 269 g
      carbohydrate per day. Animal-based foods accounted for 49% and 36% of protein and
      lipid sources, respectively, but fish and shellfish contributed only 11% for
      protein and essentially nil for lipid. Lunch was the most substantial meal of the
      day. When classified by age (i.e., 22-29, 30-39 and 40-66 year-old groups), no
      age-related difference was detected among the three groups in all nutrients
      except for crude fiber. Comparison with recommended dietary allowance (RDA) for
      Taiwanese, the insufficiency ratios were more than 50% for minerals (i.e., Fe and
      Ca) and vitamins (except for vitamin C). Excess in the lipid energy ratio (> 30%)
      was observed in 60% of the study population. In agreement with this high lipid
      intake, 17% of the participants had BMI of > 25, and triglyceride levels were
      elevated (> 150 mg/100 ml) in 27%. There were no anemic case despite the low Fe
      intake (14 mg/day).

PMID- 9163851
TI  - Indomethacin enhances the cytotoxicity of VCR and ADR in human pulmonary
      adenocarcinoma cells.
AB  - The ability of anti-inflammatory agents to modulate cellular sensitivity to
      anticancer drugs was investigated for pulmonary carcinoma cells in vitro. We
      examined the drug sensitivity of two pulmonary adenocarcinoma cell lines (76-2,
      77-4) in the presence of two drugs, an anticancer drug and an anti-inflammatory
      agent, for 72 hr by the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay with 96 well plates. Anticancer drugs used for screening test
      were cyclophosphamide (CPM), mitomycin C (MMC), adriamycin (ADR), 5-fluorouracil
      (5FU), vindesine (VDS), cisplatin (CDDP), cytarabine (Ara C), methotrexate (MTX),
      etoposide (VP-16), and vincristine (VCR). Anti-inflammatory agents examined as
      modulators to anticancer drugs were aspirin, mefenamic acid, ibuprofen, sulindac,
      piroxicam, phenacetin, dicrofenac, ketoprofen, tolmetin and indomethacin.
      Screening tests showed indomethacin to be the most effective modulator, resulting
      in more than a 3-fold increase in cytotoxicity of VCR as compared with that
      produced by VCR alone. Study of each of the ten anticancer drugs in combination
      with indomethacin showed VCR to be the most effective anticancer drug in this
      combination. In 76-2 cells, the concentration of VCR producing 50% growth
      inhibition (IC50) for VCR alone and VCR in combination with 2 micrograms/ml
      indomethacin were 1.58 +/- 0.16 and 0.52 +/- 0.1 ng/ml respectively, which
      represents a 3-fold decrease. In 77-4 cells, the IC50 for VCR alone and VCR in
      combination with 2 micrograms/ml indomethacin were 2.86 +/- 0.2 and 0.52 +/- 0.11
      ng/ml respectively, which represents a 3.8-fold decrease. Our studies indicate
      that clinically achievable concentrations of indomethacin may be useful in
      modulating VCR resistance in human pulmonary adenocarcinoma cells, so that
      combined use of VCR and indomethacin may be of potential clinical significance in
      the treatment of lung cancer.

PMID- 9163852
TI  - A case of female adnexal tumor of probable Wolffian origin: histologically, tumor
      cells showed three different patterns.
AB  - We report a 63-year-old woman with a female adnexal tumor of probable Wolffian
      origin, which arose within the leaves of the broad ligament, connected to the
      left ovary and the fallopian tube. She remains alive without evidence of disease
      2 years after left salpingo-oophorectomy without subsequent adjuvant therapy.
      Microscopically, tumor cells were arranged in three different patterns; closely
      packed tubules, solid, and sieve-like. Cells had uniform round or oval nuclei and
      mitoses were rare. Although the majority of these tumors are benign, a few cases
      have shown malignant potential. Therefore, such tumors should receive careful
      follow-up for possible recurrence and/or metastasis.

PMID- 9163850
TI  - Slight but significant improvement of insulin resistance of Wistar fatty rats by
      treatment with a disaccharidase inhibitor, AO-128.
AB  - To know whether the insulin resistance is improved by delaying carbohydrate
      absorption from the small intestine, we studied the effect of a disaccharidase
      inhibitor, AO-128, on insulin resistance of Wistar fatty rats. Rats were kept on
      standard laboratory chow with and without 10 ppm of AO-128 for 4 weeks, and then
      subjected to the glucose clamp. At the end of the 4-week treatment, plasma
      glucose level at 14:00 to 16:00 of AO-128 treated rats was 121 +/- 14 mg/100 ml
      (mean +/- S.D.), significantly lower than 226 +/- 72 mg/100 ml of the rats
      without AO-128. During clamp steady state under 20 mU.kg (-1).min (-1) continuous
      insulin infusion, glucose uptake of AO-128 treated rats was only 7.62 +/- 0.70
      mg.kg (-1). min (-1), not different from 6.64 +/- 0.91 mg.kg (-1).min (-1) of
      rats without AO-128, but much lower than the lean littermates (20.81 +/- 3.11
      mg.kg (-1).min (-1)). However, the percent suppression of hepatic glucose output
      was 55.2 +/- 23.8%, which, though incomplete, was significantly higher than 17.4
      +/- 11.2% of rats without AO-128. The present study suggested that there were at
      least two, components of insulin resistance, a genetically determined and a poor
      glycemic control-related, and that the latter insulin resistance was ameliorated
      by AO-128.

PMID- 9163853
TI  - Microangiopathic hemolytic anemia and thrombocytopenia in a child with atrial
      septal defect and pulmonary hypertension.
AB  - Microangiopathic hemolytic anemia and thrombocytopenia have been reported in
      patients with primary pulmonary hypertension, but not in patients with congenital
      heart disease even if accompanied with pulmonary hypertension. We present a 7
      year-old boy with atrial septal defect and pulmonary hypertension who developed
      microangiopathic hemolysis and thrombocytopenia. Microangiopathic hemolytic
      anemia and thrombocytopenia should be remarked as a complication in patients with
      congenital heart disease.

PMID- 9163854
TI  - Tubal endometriosis diagnosed within one month after menarche: a case report.
AB  - A 13-year-old nulligravida girl, 158.5 cm in height and 76.0 kg in body weight,
      came to our department complaining of continuous right lower abdominal pain. One
      month earlier, an ovarian cyst in the right ovary, about 3 cm in diameter, was
      found when she underwent appendectomy at another hospital, but was left
      untreated. Menarche occurred at the age of 13 years and 1 month, which was after
      the appendectomy and 24 days before the present operation. Right hematosalpinx
      with peripheral obstruction and a para-ovarian serous cyst on the same side were
      diagnosed, and therefore right salpingectomy with para-ovarian cyst resection was
      performed. The bilateral ovaries and uterus were completely normal by inspection.
      The post operative histological examination confirmed hematosalpinx and revealed
      tubal endometriosis.

PMID- 9163855
TI  - Cavocaval liver transplantation without venovenous bypass and without temporary
      portocaval shunting: the ideal technique for adult liver grafting?
AB  - The influence of the implantation technique on the outcome was studied
      prospectively in a series of 116 consecutive adult patients undergoing primary
      liver transplantation during the period January 1991-June 1994. Thirty-eight
      patients (32.8%; group 1) underwent classical orthotopic liver transplantation
      (OLT) with replacement of the recipient's inferior vena cava (R-IVC) and with
      venovenous bypass (VVB). Thirty-nine patients (33.56%) had a piggy-back OLT with
      preservation of the R-IVC (group 2); bypass was used in 17 of them (43.6%)
      because of poor hemodynamic tolerance of R-IVC occlusion. Thirty-nine patients
      (33.6%) had OLT without VVB and with side-to-side cavocaval anastomosis (group
      3). The three techniques were performed irrespective of the anatomical situation
      and of the status of the recipient at the time of transplantation. The following
      parameters were assessed in all patients: implantation time, blood product use,
      morbidity (e.g., hemorrhagic, thoracic, gastrointestinal, neurological, and renal
      complications), and outcome. Thirty-one patients underwent detailed
      intraoperative hemodynamic assessment. The early (< 3 months) post-transplant
      mortality of 10.3% (12/116 patients) was unrelated to the implantation technique.
      Group 3 had a significantly shorter mean implantation time, a reduced need for
      intraoperative blood products, and a lower rate of reoperation due to intra
      abdominal bleeding. After excluding two immediate perioperative deaths and eight
      patients requiring early retransplantation because of primary nonfunction, the
      frequency of immediate extubation was significantly higher in group 3. Detailed
      hemodynamic assessment did not show a difference between 6 group 1 patients and
      17 group 3 patients, indicating that partial lateral clamping of the IVC fulfills
      the function of venous bypass. Similar results were obtained in 6 group 2
      patients who did not have IVC occlusion. Cavocaval OLT has become our preferred
      method of liver implantation. It allows the transplantation to be performed
      without VVB, regardless of the anatomical situation and of the condition of the
      patient at the time of transplantation. Moreover, it avoids all of the potential
      complications and costs of VVB.

PMID- 9163856
TI  - Percutaneous technique for venovenous bypass including a heat exchanger is safe
      and reliable in liver transplantation.
AB  - We have introduced and evaluated several modifications of the conventional
      venovenous bypass (VVBP) in 29 adult patients undergoing liver transplantation
      (OLT). A percutaneous technique for insertion of a jugular venous return cannula
      and a femoral vein cannula was applied. The inferior mesenteric vein (IMV) was
      used for splanchnic decompression, which facilitated dissection of the recipient
      liver and allowed portal anastomosis to be performed without disconnecting the
      portal bypass. A heat exchanger was introduced into the bypass circuit to prevent
      heat loss. The percutaneous technique prevented complications related to
      dissection in the axilla and groin. Hemodynamic characteristics corresponded to
      those found using the traditional technique. Complications related to the VVBP
      were seen in only one patient in whom the femoral catheter was accidentally
      introduced into the femoral artery. We conclude that percutaneous cannulas, use
      of the IMV for splanchnic decompression and the introduction of a heat exchanger
      offer significant benefits and that they are safe and reliable.

PMID- 9163857
TI  - Pancreas-specific protein (PASP), serum amyloid A (SAA), and neopterin (NEOP) in
      the diagnosis of rejection after simultaneous pancreas and kidney
      transplantation.
AB  - A reliable, noninvasive indicator of pancreatic allograft rejection is urgently
      needed. In this study, serum (S), plasma (P), and urine (U) levels of pancreas
      specific protein (P-PASP, U-PASP), neopterin (S-NEOP, U-NEOP), amylase (U-AMYL),
      and amyloid A (SAA) were measured daily in ten type I diabetic patients following
      simultaneous pancreas and kidney transplantation (SPK). Rejection episodes
      occurred in three isolated pancreas, nine isolated kidney, and five simultaneous
      pancreas and kidney transplants. In the case of the eight pancreas rejections,
      SAA was the rejection marker with the highest diagnostic accuracy (94%). Using P
      PASP and U-PASP, an accuracy of 81% and 79%, respectively, was achieved. During
      viral infections, U-NEOP levels increased to a maximum level of 1904 mumol/mol
      creatinine, whereas during bacterial infections, SAA levels increased to a
      maximum value of 43 mg/dl. SAA, measured for the first time in SPK, appears to be
      a valuable rejection parameter. In combination with U-NEOP and U-AMYL, a
      differential diagnosis between rejection, bacterial infection, and viral
      infection was possible. Neither U-PASP nor P-PASP monitoring led to a significant
      improvement in the results.

PMID- 9163858
TI  - Value of mucosal biopsies in the monitoring of acute small bowel rejection.
AB  - The value of mucosal biopsies in evaluating small bowel rejection is
      controversial. In this study, the value of mucosal biopsies was estimated in
      unmodified porcine small bowel rejection. Ten animals received the distal half of
      the small bowel as a heterotopic loop (Thiry-Vella loop). The allografts were
      followed by proximally and distally harvested full-thickness and mucosal biopsies
      every other day, starting from the 3rd day and continuing until the grafts became
      necrotic. The histological parameters in both types of biopsies were
      semiquantitatively scored from 0 to 3 and compared with each other. The
      difference in mean values on the subsequent days was not remarkable, the results
      favoring slightly higher values in full-thickness than in mucosal biopsies. Our
      results suggest that multiple mucosal biopsies are adequate in monitoring
      morphological changes of small bowel grafts during rejection and that the
      proximal and distal ileum are similarly affected by acute rejection.

PMID- 9163859
TI  - Post-transplantation diabetes is better controlled after conversion from
      prednisone to deflazacort: a prospective trial in renal transplants.
AB  - It is well known that long-term use of steroids plays a decisive role in the
      development of glucose intolerance and diabetes mellitus (DM). Deflazacort, an
      oxazoline derivative of prednisolone, has been introduced as a potential
      substitute for conventional steroids in order to ameliorate glucose intolerance.
      We initiated a randomized study of conversion from prednisone to deflazacort in
      kidney transplantation (Tx) recipients presenting with pre-Tx or post-Tx DM to
      ascertain whether or not the switch to deflazacort would ameliorate the diabetic
      state. Forty-two recipients in the conversion group were compared with 40
      patients on prednisone (the control group) in a prospective manner. The dose
      reduction of insulin or oral blood glucose-lowering agents, the adequacy of
      glucose control, and the development of side effects were the criteria for
      evaluating outcome. In the conversion group, patients were switched to a
      deflazacort at a dose ratio of 6 mg deflazacort to 5 mg prednisone. During the
      mean follow-up period of 13.2 months, neither graft dysfunction nor acute
      rejection developed in the conversion group. Improvement in blood glucose control
      in the conversion group was noted. When the conversion group was stratified into
      pre- or post-Tx DM, promising effects were clearly evident in the post-Tx DM
      patients. More than 50% dose reduction of blood glucose-lowering agents was
      possible in 42.3% of post-Tx DM patients. In conclusion, it was readily possible
      to control blood glucose better in post-Tx DM recipients without seriously
      affecting the immunosuppressive activity after conversion to deflazacort.

PMID- 9163860
TI  - Adenovirus-mediated gene transfer using in-situ perfusion of the liver graft.
AB  - To establish an efficient technique for adenovirus-mediated gene transfer in
      liver transplantation, we evaluated the in situ perfusion of liver grafts. The
      grafts were perfused in situ with 1 x 10(10) of E1-deleted, replication-defective
      adenoviral vectors encoding the LacZ gene driven by the human CMV promoter,
      either through the hepatic artery (group 1) or the portal vein (group 2). Group 3
      animals served as negative controls; their liver grafts were perfused with
      lactated Ringer's solution through the portal vein. PCR confirmed the presence of
      viral DNA in every graft perfused with viral vectors. In X-gal staining, positive
      staining was observed almost exclusively at the portal triad in group 1, whereas
      in group 2 minimal staining was observed, predominantly in the parenchymal area.
      Protein production from the transfected gene was confirmed by a functional
      protein assay; the values were 0.16% +/- 0.07% liver protein in group 1, 0.13% +/
      0.02% in group 2, and 0.007% +/- 0.0003% in group 3 on postoperative day 2. In
      conclusion, in situ perfusion of the viral vectors through the hepatic artery
      resulted in an effective expression of the transfected gene, predominantly at the
      portal triad.

PMID- 9163861
TI  - The effect of cyclosporin on endothelin levels after orthotopic liver
      transplantation in rats.
AB  - To assess the effects of cyclosporin (CyA) on endothelin-1 (ET-1) in rat liver
      allograft rejection, we evaluated ET-1 expression in samples obtained from
      BN(RT1n)-to-BN (group 1) rats, DA(RT1a)-to-BN (group 2) rats, and DA-to-BN rats
      treated with 5 mg/kg per day of CyA (group 3). Serum and hepatic ET-1 levels,
      determined by a radioimmunoassay, remained unchanged in group 1. In group 2, the
      ET-1 levels peaked on postoperative day (POD) 5 in the liver at 344 +/- 31.6 pg/g
      wet, and on POD 7 in the serum at 38.7 +/- 13.1 pg/ml. In group 3, hepatic and
      renal ET-1 levels showed a progressive increase until POD 10, while serum ET-1
      levels remained unchanged. In conclusion, acute rejection caused a temporary
      increase in the ET-1 level in both the serum and the liver in the early
      postoperative period what might have been caused by endothelial damage due to
      ongoing, acute rejection. CyA caused a time-dependent increase in the ET-1 level
      in both the liver and the kidney without an increase in the serum ET-1 level. The
      serum ET-1 level might have been affected by the clearance of ET from the liver
      or kidney.

PMID- 9163862
TI  - Conventional and quantitative liver function tests after hepatic transplantation:
      a prospective long-term follow-up.
AB  - In long-term survivors of liver transplantation, hepatic function is obviously of
      vital importance. Therefore, we prospectively performed conventional and
      quantitative liver function tests in patients who had survived a first
      transplantation for at least 4 years. Compared to 6 months after transplantation,
      serum bilirubin concentration and gamma GT activity were significantly lower
      after 3, 4, and 5 years (bilirubin 1.2 +/- 0.2 mg/dl at 6 months vs 1.0 +/- 0.1,
      1.0 +/- 0.2, and 0.8 +/- 0.1 mg/dl respectively; gamma GT 106 +/- 0 33 U/l at 6
      months vs 56 +/- 17, 67 +/- 35, 39 +/- 10 U/l respectively). At these points in
      time, blood levels of cyclosporin A were also significantly lower. Other
      parameters of liver cell function and liver cell integrity (AP, AST, ALT, GLDH,
      total protein, thromboplastin time, partial thromboplastin time) were unchanged
      over time. Serial quantitative liver function tests (indocyanine green half-life,
      galactose elimination capacity, lidocaine half-life, and MEGX formation) also
      remained stable. Thus, we conclude that hepatic function remains stable in long
      term survivors of liver transplantation for at least several years.

PMID- 9163863
TI  - A pharmacokinetic comparison of the corn oil versus microemulsion gelcap
      formulation of cyclosporin used de novo after renal transplantation.
AB  - The initial poor absorption of the corn oil-based, gel capsule oral formulation
      of cyclosporin (CyA) greatly limits its use for inception of immunosuppressive
      therapy. Insufficient drug concentrations during the early post-transplant period
      predispose to renal allograft rejection. The present study served to compare the
      time required to achieve the therapeutic CyA concentrations after de novo
      administration of the corn oil-based gel capsule (CyA-GC; n = 11) versus the
      microemulsion (CyA-ME; n = 11) formulation of CyA. During the 1st month after
      renal transplantation, patients underwent serial pharmacokinetic profiling from
      which we obtained observed and dose-corrected values of several parameters.
      Although patients in neither the CyA-GC nor the CyA-ME group adequately absorbed
      the drug during days 0-2, from day 3 to 4 patients in the CyA-ME group showed
      significantly greater absorption than those in the CyA-GC group (P = 0.041).
      Patients in the CyA-ME group reached the 1st month target average concentration
      (Cav) values (> or = 550 ng/ml) earlier than those in the CyA-GC group and
      required significantly lower daily CyA doses (P = 0.018). We conclude that
      therapeutic CyA levels can be achieved more rapidly and with lower doses of the
      drug after de novo administration of CyA-ME than with CyA-GC.

PMID- 9163864
TI  - Mycophenolate mofetil added to immunosuppression after liver transplantation-
      first results.
AB  - Mycophenolate mofetil (MMF) has been used successfully as an immunosuppressive
      agent after kidney and heart transplantation, but experience with MMF after liver
      transplantation is still limited. Between August 1995 and January 1996, we
      treated 20 patients with MMF after orthotopic liver transplantation in an open,
      prospective study. Five out of eight patients with acute rejection and one
      patient with early chronic rejection showed a complete response after MMF was
      added to the immunosuppression. Three patients with chronic rejection did not
      improve, one died, and two have stable graft function at present. In eight
      patients who suffered from toxicity, a reduction in the dosage of tacrolimus was
      attempted with simultaneous MMF therapy. One patient died due to multiple organ
      failure. Liver function improved completely in one other patient, and partially
      in three patients after adding MMF. In the remaining three patients, a reduced
      dosage of tacrolimus or cyclosporin, together with MMF, reduced toxicity, not
      significantly. In conclusion, MMF appears to be a safe and potentially useful
      adjuvant immunosuppressive agent for rescue and maintenance therapy.

PMID- 9163865
TI  - Liver transplantation for the treatment of fulminant hepatic failure induced by
      the ingestion of ecstasy.
AB  - Methylenedimethoxymethamphetamine (MDMA), more commonly known as ecstasy, is a
      synthetic amphetamine derivative used by teenagers and young adults in the United
      States as well as in Western Europe as a "dance drug". Though a number of
      complications associated with this drug have been reported, there is little
      information pertaining to hepatoxity as a result of MDMA ingestion. This case
      report is about an 18-year-old female patient who regularly used ecstasy on
      weekends over a 2-month period. Within 2 days after accepting a "hit" of the
      substance at a party, she was admitted to the hospital because of lethargy,
      vomiting, abdominal pain, stool discoloration, icterus, and darkened urine. On
      day 7 she developed fulminant hepatic failure with reduced hepatic coagulation
      factors and grade IV encephalopathy. Orthotopic liver transplantation was carried
      out 10 days following the ingestion. The patient made a full recovery within 72 h
      and was released from the hospital 6 weeks later. Histopathological examination
      of the removed liver revealed a nutritive-toxic liver necrosis. This case
      demonstrates that the ingestion of ecstasy, even on an infrequent basis, can lead
      to acute fulminant liver necrosis, and that this life-threatening complication
      can be treated successfully by liver transplantation.

PMID- 9163866
TI  - Papillitis and vasculitis of the arteria spinalis anterior as complications of
      hepatitis C reinfection after liver transplantation.
AB  - It is well known that hepatitis C virus (HCV)-related chronic liver disease may
      be associated with various immunological disorders including mixed
      cryoglobulinemia, which is accompanied by cutaneous vasculitis, arthralgias,
      membrano-proliferative glomerulonephritis, and neuropathy in association with
      cryoprecipitable immune complexes in serum. We describe here the first case of
      central nervous system HCV infection with evidence of the virus in the
      cerebrospinal fluid in association with cryoglobulinemia in a patient who
      developed recurrent episodes of papillitis and vasculitis of the arteria spinalis
      anterior after liver transplantation.

PMID- 9163867
TI  - Is cytomegalovirus a cause of ureteral stricture in renal transplant recipients?
AB  - Cytomegalovirus (CMV) is regarded as a predominant infectious agent in solid
      organ transplants. CMV disease has highly protean clinical manifestations.
      Nevertheless, urinary tract involvement seems to be very rare during CMV
      infection. We report two cases of renal transplant recipients in whom ureteral
      stricture developed in the course of CMV disease. Histologic data were available
      for them and were consistent with CMV infection. We discuss previous case reports
      and propose physiopathologic mechanisms.

PMID- 9163868
TI  - Liver transplantation in patients with Caroli's disease and recurrent
      cholangitis.
AB  - Caroli's disease is an uncommon congenital disorder of the intrahepatic biliary
      tree. It is characterized by multiple and segmental dilatations of the bile
      ducts. The clinical course of Caroli's disease is often complicated by recurrent
      episodes of bacterial cholangitis that seriously impair the patient's quality of
      life. Despite wide spectrum antimicrobial agents, medical treatment of
      cholangitis is frequently unsuccessful in patients with Caroli's disease due to
      the persistence of bacteria in dilatated bile ducts. Other therapies, including
      internal or external biliary drainages and various surgical or endoscopic
      procedures, have been used in the treatment of Caroli's disease, with poor
      results. There are no previous reports in the literature of liver transplantation
      for recurrent cholangitis in patients with Caroli's disease. We present two such
      cases, in which cholangitis is resolved.

PMID- 9163869
TI  - Successful regrafting of a transplanted liver.
AB  - We report on the successful regrafting of a transplanted liver. The donor liver
      was first grafted into a patient suffering from cryptogenic cirrhosis; the
      patient died 1 day after the elective transplantation of cerebral bleeding. The
      well-functioning graft was harvested again and transferred to our institution.
      After another 12 h of cold ischemia, the liver was reperfused in an urgently
      registered patient with recurrence of hepatitis B in his first graft. The
      transplantation was successfully performed and the patient is now doing well,
      more than 5 months after regrafting with the reused liver.

PMID- 9163870
TI  - A novel technique for reconstruction of the proximal alimentary tract after bowel
      transplantation for intestinal pseudo-obstruction.

PMID- 9163871
TI  - No tolerance induction with cryopreserved bone marrow cells after allogeneic
      kidney transplantation and antilymphocyte globulin in rhesus monkeys.

PMID- 9163872
TI  - Angora mouse mutation: altered hair cycle, follicular dystrophy, phenotypic
      maintenance of skin grafts, and changes in keratin expression.
AB  - Angora is an autosomal recessive mouse mutation caused by a deletion of
      approximately 2 kilobases in the fibroblast growth factor 5 (Fgf5) gene.
      Phenotypically, homozygous angora (Fgf5go/Fgf5go) mice have excessively long
      truncal hair and can be differentiated from heterozygous (+/Fgf5go) and wild-type
      (+/+) littermates by 21 days of age. Abnormal hair length is due to a
      prolongation of the anagen phase of the hair cycle of approximately 3 days. In
      addition, widely scattered hair follicles produce structurally defective hair
      shafts that twist within the follicle, presumably causing secondary hyperplasia
      of the outer root sheath and epidermis adjacent to the follicle. These follicular
      abnormalities were accentuated by immunohistochemical detection of mouse specific
      keratin 6, a nonspecific marker of epidermal hyperplasia. These abnormalities
      could be identified from birth throughout life in angora mice genotyped by
      polymerase chain reaction techniques. Moreover, the long truncal hair phenotype
      was maintained in skin grafted onto C.B-17/Sz-scid/scid mice that had normal
      pelage hairs and hair cycles, suggesting that circulating or diffusible humoral
      factors regulating the mouse hair cycle are not involved in this mutation. The
      angora mutation provides another useful mouse model for studying the hair cycle
      and its modulation.

PMID- 9163873
TI  - Immunohistochemical identification of caprine arthritis-encephalitis virus in
      paraffin-embedded specimens from naturally infected goats.
AB  - The expression of caprine arthritis-encephalitis virus capsid protein was studied
      in seropositive naturally infected asymptomatic goals (10< seropositive naturally
      infected encephalitic kids (12) and goats (4), and noninfected control goats (3).
      Rabbit antiserum to recombinant viral capsid and matrix proteins were used in a
      biotin-streptavidin-alkaline phosphatase complex immunohistochemical method on
      sections of formalin- and ethanol-fixed tissue specimens. Macrophages in inflamed
      areas of the lung (8/12), in the brain (5/16), and in the spinal cord (4/16) from
      encephalitic animals harbored viral antigens, as revealed by immunohistochemistry
      and use of a capsid protein-specific antiserum. Altogether 12/16 encephalitic
      animals tested positive for viral antigen. Viral antigens were found in 5/10
      seropositive asymptomatic goals in macrophages located in the lung (3), the udder
      (1), and the medulla of lymph nodes (4). None of the control animals tested
      positive for viral antigen. Ethanol fixation showed highest sensitivity, and the
      lowest antigen concentration that revealed a positive signal discernible from
      background was twofold higher in ethanol-fixed specimens than in formalin-fixed
      specimens. The evaluation was performed on artificial antigen substrates embedded
      with defined concentrations of recombinant viral capsid protein.
      Immunohistochemistry is a valuable supplement to the methods presently available
      for diagnosis in cases suspicious of caprine arthritis-encephalitis.

PMID- 9163874
TI  - Encephalitozoon hellem in budgerigars (Melopsittacus undulatus).
AB  - Microsporidiosis with concurrent megabacteriosis in budgerigar (Melopsittacus
      undulatus) chicks contributed to significant economic floss in a commercial pet
      bird aviary in Mississippi. Three budgerigar chicks, 1-2 weeks old, from the
      aviary were necropsied. Microscopic lesions in the chicks consisted of heavy
      infection of enterocytes with microsporidia (2/3; autolysis precluded critical
      evaluation of the intestine of chick No. 2), multifocal hepatic necrosis and
      inflammation with intralesional microsporidia (1/3), spherical clusters of
      microsporidia in the hepatic sinusoids in the absence of inflammation (1/3), and
      gastric megabacteriosis (3/3). The ultrastructure of the microsporidian spores
      was consistent with an Encephalitozoon species. The polymerase chain reaction and
      Southern blot analysis were used to identify the microsporidian as
      Encephalitozoon hellem, an organism that has only been identified in humans.
      Encephalitozoon hellem causes keratoconjunctivitis and respiratory infections in
      humans with acquired immunodeficiency syndrome. This report presents the first
      confirmed case of microsporidiosis in budgerigars. The finding of E. hellem in
      pet birds may be important in elucidating the epidemiology of human infections
      with this organism.

PMID- 9163875
TI  - Necrotic oophoritis in gilts associated with experimental inoculation of a viral
      gene-deletion mutant pseudorabies vaccine.
AB  - Previous work on the reproductive effects of various herpesviruses has
      demonstrated adverse effects on reproductive function in several host species.
      Although herpesviral vaccines are used in several species to ameliorate the
      clinical effects of infection, pathogenicity for reproductive tissue, associated
      with diminished reproductive efficiency, has been reported to be retained in a
      live-attenuated vaccine strain of the herpesvirus, bovine herpesvirus-1. The
      objective of this study was to determine if a gene-deletion mutant, thymidine
      kinase negative, pseudorabies virus retained acute pathogenicity for the
      reproductive tract of swine following intravenous inoculation during estrus.
      Estrous cycles of nulliparous gilts were synchronized by administration of a
      gonadotropin and daily exposure to a boar. During estrus, six gilts were
      inoculated intravenously with twice the recommended intramuscular dose of a
      commercially available viral gene-deletion mutant pseudorabies vaccine. Six
      control gilts in estrus were sham inoculated intravenously with vaccine diluent
      during estrus. All animals were euthanatized 10 days postinoculation, and the
      ovaries and uterus were collected for histopathology following gross examination.
      All reproductive tracts were grossly normal. Histologically, four of six treated
      gilts had a mild to moderate, multifocal, necrotizing oophoritis, with the
      lesions limited to corpora lutea and the adjacent stroma. Ovaries of control
      gilts exhibited to necrotizing lesions. Both control and pseudorabies vaccine
      inoculated gilts had occasional minimal focal mononuclear infiltrates in the
      ovaries. These data show that live attenuated viral gene-deletion mutant
      pseudorabies vaccine administered to swine during estrus can result in acute
      pathogenicity in ovarian corpora lutea. No endocrinologic data is available in
      these pigs, so the impact on pregnancy maintenance is unknown.

PMID- 9163876
TI  - Differential levels of mRNAs for cytokines, the interleukin-2 receptor and class
      II DR/DQ genes in ovine interstitial pneumonia induced by maedi visna virus
      infection.
AB  - The relative levels of selected cytokine, interleukin-2 receptor, class II DR and
      DQ RNAs, and maedi visna virus (MVV) RNA were measured by reverse-transcriptase
      polymerase chain reaction (RT-PCR) in the lungs of sheep with natural maedi visna
      virus infection (n = 8) and a group of age/sex/breed-matched MVV seronegative
      sheep (n = 4). These animals were divided into two groups, irrespective of
      serostatus, according to the severity of lymphocytic interstitial pneumonia. The
      severity of lung lesions was determined by clinical sign, lung weight, and lesion
      sore in the lungs measured by three pathologic parameters. Sheep with lung
      lesions showed hyperelevated levels of granulocyte-macrophage colony-stimulating
      factor upregulated gamma-interferon, interleukin 2 receptor, and interleukins 1
      beta, 4, and 10 mRNAs. Class II mRNAs were found not to be elevated in the lungs
      of sheep with lung lesions. Tumor necrosis factor alpha and transforming growth
      factor beta 1 mRNA levels were similar in all sheep lungs studied. We discuss the
      major roles played by granulocyte-macrophage colony-stimulating factor and type 2
      cytokines in the pathogenesis of this disease and the possible stimulation of the
      production of these cytokines by viral surface glycoproteins.

PMID- 9163877
TI  - Characterization of the proliferation state in canine mammary tumors by the
      standardized AgNOR method with postfixation and immunohistologic detection of Ki
      67 and PCNA.
AB  - Paraffin-embedded tissue sections of 96 surgically removed mammary tumors from
      female dogs were analyzed for their proliferation state using three different
      methods. The AgNOR method, originally developed by Ploton and coworkers in 1986,
      modified and standardized by the AgNOR committee, is an easy, inexpensive silver
      staining procedure used to determine cell proliferation and prognosis of various
      tumors. Due to the standardized staining protocol of the AgNOR method and a
      postfixation step, results obtained were of excellent quality for image-analysis
      processing. The growth fraction was evaluated by counting of immunohistologically
      positive-stained cells for Ki-67 or proliferating-cell nuclear antigen (PCNA).
      The values determined were, in general, lower with Ki-67 (MIB1) than with PCNA
      (PC10). Nevertheless, the labeling indices of these antigens correlated
      significantly (P < 0.001). Though the differences of the means between the tumor
      groups according to the classification system of the World Health Organization
      were significant for all three investigated methods (P < 0.001), there was a
      considerable overlap between the tumor groups concerning all investigated
      parameters. An exploratory data analysis (multivariate analysis) as performed to
      evaluate the prognostic relevance of the three methods including further
      anamnestic, clinical, gross, and histopathologic variables. Besides the
      histopathologic diagnosis (survival P < 0.001; survival time P < 0.05;
      reappearance of tumor growth P < 0.05), only the PCNA-labeling index (time until
      reappearance of tumor growth P < 0.001) was of prognostic significance.

PMID- 9163878
TI  - The immunophenotypic characterization of bovine lymphomas.
AB  - A prospective analysis of 38 cases of bovine lymphoma was performed. Thirty-five
      of the lymphomas were considered enzootic because of serologic or molecular
      biologic association with the bovine leukemia virus (BLV). The three remaining
      cases were in cattle < 1 year of age and were not associated with BLV and hence
      were considered sporadic lymphomas. Utilizing the national cancer Institute
      Working Formulation for the morphologic classification of human non-Hodgkin's
      lymphoma, 54.3% (19/35) of the enzootic lymphomas were classified as the diffuse
      large cleaved cell type. The cells of the 35 enzootic lymphomas expressed a
      consistent immunophenotype represented by MHCII+, gamma-heavy chain+, and lambda
      light chain+; this constellation of markers indicated a mature B-cell phenotype.
      The three sporadic lymphomas failed to express MHCII antigen despite the presence
      of other B-cell antigens. There was no correlation between morphologic cell type
      and immunophenotype in these bovine lymphomas.

PMID- 9163879
TI  - Helicobacter mustelae-associated gastric adenocarcinoma in ferrets (Mustela
      putorius furo).
AB  - Helicobacter pylori in humans is associated with active, chronic gastritis,
      peptic ulcer disease, and most recently has been linked epidemiologically to
      gastric adenocarcinoma. A related organism, Helicobacter mustelae, naturally
      infects ferrets and also causes a persistent gastritis, a precancerous lesion,
      and focal glandular atrophy of the proximal antrum. In this report, we document
      the clinical presentation and histopathologic confirmation of H. mustelae
      associated gastric adenocarcinoma in two middle-aged male ferrets. The ferret
      appears to be well suited to study the pathogenesis of naturally occurring
      Helicobacter sp.-induced gastric adenocarcinoma.

PMID- 9163880
TI  - Testicular efferent ductule cyst of a dog.
AB  - A 9-year-old male Shetland Sheepdog had a small mass in the left testis. Grossly,
      the round to oval cyst was present at the upper pole of the testicular parenchyma
      near the head of the epididymis. Histologically, the cyst was lined by a single
      layer of nonciliated and ciliated epithelial cells. Immunohistochemically, the
      epithelial cells of the cyst showed expression of the low- and high-molecular
      weight cytokeratins, vimentin, and desmin similar to that of normal efferent
      ductules in the dog. The testicular cystic dysplasia was thought to originate
      from the efferent ductules.

PMID- 9163881
TI  - Apocrine gland tumor of the eyelid in a dog.
AB  - A 13-year-old male Shetland Sheepdog with progressive exophthalmos had a
      neoplastic mass in the ocular adnexa. Histologically, this neoplasm was composed
      of duct-forming epithelial cells with decapitation secretion. Tumor cells invaded
      the globe through the tunica conjunctiva and replaced the vitreous body. The
      cornea, iris, ciliary body, and retina were extensively destroyed. Both the
      epithelial and spindle-shaped myoepithelial cells showed nuclear atypia and
      mitotic activity in the globe. The primary tumor was diagnosed as adenocarcinoma,
      probably originating from apocrine sweat glands of the eyelid, and the
      infiltrating intraocular neoplasm was diagnosed as a malignant mixed tumor.

PMID- 9163882
TI  - Intraerythrocytic inclusions associated with iridoviral infection in a fer de
      lance (Bothrops moojeni) snake.
AB  - Intraerythrocytic inclusions associated with infection by an iridovirus were
      observed in a fer de lance (Bothrops moojeni) snake that was being evaluated for
      the presence of renal carcinoma. The erythrocytes contained two types of
      inclusions, one viral and one crystalline, usually concomitantly. The snake was
      markedly anemic and exhibited a marked regenerative response. Ultrastructural
      analysis identified the virus to be an iridovirus consistent with snake
      erythrocyte virus and the crystalline structures to be of a different nature than
      hemoglobin.

PMID- 9163883
TI  - Primary amebic meningoencephalitis due to Naegleria fowleri in a South American
      tapir.
AB  - Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris are known to
      cause fatal central nervous system (CNS) disease in human beings. N. fowleri
      causes acute, fulminating primary amebic meningoencephalitis (PAM), which
      generally leads to death within 10 days. Acanthamoeba spp. and B. mandrillaris
      cause chronic granulomatous amebic encephalitis, which may last for 8 weeks.
      Acanthamoeba spp. and B. mandrillaris also cause CNS disease in animals. N.
      fowleri, however, has been described only in human beings. This report is the
      first of PAM in an animal, a South American tapir. Dry cough, lethargy, and coma
      developed in the animal, and its condition progressed to death. At necropsy,
      lesions were seen in the cerebrum, cerebellum, and lungs. The CNS had severe,
      suppurative meningoencephalitis with many neutrophils, fibrin, plasma cells, and
      amebas. Amebas were 6.5 microns to 9 microns in diameter and had a nucleus
      containing a large nucleolus. Amebas in the sections reacted with a monoclonal
      antibody specific for N. fowleri in the immunofluorescent assay and appeared
      bright green.

PMID- 9163884
TI  - Malignant cauda equina paraganglioma in a cat.
AB  - An 11-year-old spayed female domestic long-haired cat presented for surgical
      removal of a slowly growing and deeply invasive 2.5 x 3.5-cm mass cranial to the
      base of the tail. Light microscopic examination of surgical biopsy specimens
      revealed an encapsulated mass composed of packets of polygonal cells of various
      sizes separated by a delicate fibrovascular stroma. Gomori's reticulum stain
      revealed a characteristic endocrine or "Zellballen" pattern. Tumor cells
      contained diffuse positive reactivity to synaptophysin and neuron-specific
      enolase, reactions consistent with a neuroendocrine neoplasm. S-100 protein
      positive cells reminiscent of sustentacular (support) cells occurred singly or in
      small clusters within tumor packets. At postmortem examination 3 months later, a
      9- x 5- x 4-cm multinodular raised tan mass involving the caudal pelvis, sacrum,
      and tail-head regions was found. The base of this neoplastic mass originated
      within the cauda equina region and involved approximately five caudal nerve
      roots. Numerous 1-3-mm metastatic nodules were identified disseminated throughout
      the pulmonary parenchyma. The tumor was diagnosed as a malignant paraganglioma of
      the cauda equina region with pulmonary metastasis.

PMID- 9163885
TI  - Intravascular malignant T-cell lymphoma (malignant angioendotheliomatosis) in a
      cat.
AB  - A 7-year-old spayed female Siamese cat was presented with a 7-day history of
      ataxia, circling to the right, and involuntary micturition and defecation.
      Cerebrospinal fluid analysis showed increased protein content and relative
      eosinophilia. At necropsy, there was flattening of the cerebral cortical gyri of
      the right frontal and parietal lobes, and both kidneys had multiple wedge-shaped
      cortical indentations. Histologically, the cerebral cortex contained several
      extensive malacic foci, and the kidneys had multifocal parenchymal degeneration
      and atrophy. There was multifocal partial to complete thrombosis of renal
      interlobar arteries and of the right middle cerebral artery and meningeal
      branches; these thrombi contained large anaplastic round cells, which often
      invaded the arterial wall. Many smaller vessels within the kidneys and brain were
      occluded with clusters of similar cells, without thrombosis or vascular wall
      invasion. The neoplastic round cells had immunohistochemical staining properties
      of T lymphocytes.

PMID- 9163886
TI  - Neuronal vacuolation in raccoons (Procyon lotor).
AB  - Microscopic vacuolar changes in neuronal perikaryon are described in two free
      ranging raccoons (Procyon lotor) from different geographic locations in the
      United States. Both animals were negative for rabies and scrapie-associated
      antigens. Microscopically, lesions were not seen in the neuropil. Neuronal
      vacuolations have previously been documented in brains of normal animals and in
      diseases such as rabies and prion-associated encephalopathies. Although
      experimental transmission of a spongiform mink encephalopathy has been documented
      in raccoons, a naturally occurring spongiform encephalopathy has not been
      described in this species. The presence of neuronal vacuolations in the raccoons
      is novel and requires further investigation to elucidate the mechanism of this
      phenomenon.

PMID- 9163887
TI  - Immunohistochemical detection of VHS virus in paraffin-embedded specimens of
      rainbow trout (Oncorhynchus mykiss): the influence of primary antibody, fixative,
      and antigen unmasking on method sensitivity.
AB  - The influence of the primary antibody, the fixative, and the antigen unmasking
      technique on the method sensitivity of immunohistochemistry as a method for the
      identification of viral hemorrhagic septicemia (VHS) virus in paraffin-embedded
      specimens of naturally infected rainbow trout (Oncorhynchus mykiss) was examined.
      Fish (200-300 g) were collected during an outbreak of VHS. Parallel specimens
      from liver, spleen, kidney, and brain were fixed by immersion in 10% phosphate
      buffered formalin, periodate-lysine-paraformaldehyde (PLP), Bouin's fluid, or
      absolute ethanol. Virus cultivation was also performed on parallel specimens, and
      the virus titer (TCID50/ml) was determined. Purified nucleocapsid protein (N
      protein) of the virus was incorporated in an artificial antigen substrate
      polymerized bovine serum albumin), fixed as described above, and embedded in
      paraffin wax. Microwave unmasking was performed on formalin-, PLP-, and Bouin's
      fluid-fixed specimens. The presence of virus peptides in situ or N-protein in the
      artificial antigen substrates was visualized using an immunohistochemical method
      based on alkaline phosphatase or peroxidase and one polyclonal and five
      monoclonal polypeptide-specific antibodies. VHS virus was identified in situ in
      specimens with high virus titers (10(7-8) TCID50/ml) regardless of the fixative
      and without the need of an unmasking procedure. A pronounced masking effect was
      observed for the cross-linking formalin and PLP fixatives. Regardless of the
      primary antibodies used, there was a significantly higher epidemiologic
      sensitivity (the proportion of virus positive samples that tested positive by
      immunohistochemistry) using ethanol and Bouin's fluid compared with formalin and
      PLP (P < 0.05). At 10(5) TCID50/ml, the average sensitivity reached 0.5, and at >
      or = 10(6) TCID50/ml, sensitivity was 0.9. Unmasking procedures showed a moderate
      effect and did not result in significantly higher epidemiologic sensitivity (P =
      0.17), There was great variation for the different monoclonal antibodies/antigens
      and fixatives. Sensitivity studies on antigen substrates were in accordance with
      results of in situ studies that showed the highest sensitivity for ethanol and
      Bouin's fluid. Virus cultivation was more sensitive than immunohistochemistry.
      This study showed that the fixative and the primary antibody both influence
      method sensitivity and that VHS virus antigens concealed during fixation are
      difficult to reexpose. Immunostaining for VHS virus should be performed with
      monoclonal antibodies specific for the N-protein, and tissue samples should be
      fixed in either ethanol or Bouin's fluid. Immunohistochemistry is specific but is
      less sensitive than virus cultivation. Immunostaining for VHS virus can be a
      valuable supplement to virus cultivation during acute outbreaks of disease.

PMID- 9163888
TI  - Salmon calcitonin and calcium in the treatment of male osteoporosis: the effect
      on bone mineral density.
AB  - OBJECTIVE: To assess the effectiveness of salmon calcitonin in the therapy of
      male osteoporosis. METHODS: Nine male patients aged 20-73 years with vertebral
      osteoporosis were included in this study. Patients were prescribed 100 units of
      salmon calcitonin injected subcutaneously three times per week over a period of
      three months, followed by three months without salmon calcitonin treatment.
      Thereafter the patients received another salmon calcitonin cycle for three months
      as described above. All men received calcium supplementation of 1000 mg/day
      throughout the study period of 12 months. Bone mineral density of the lumbar
      spine and at the hip was measured at the beginning and the end of the treatment
      period using DXA (n = 7) or QCT (n = 2). RESULTS: Baseline evaluation revealed a
      bone mineral density of the lumbar spine of 0.78 +/- 0.09 g/cm2 and 0.62 +/- 0.09
      g/cm2 at the hip. Treatment with salmon calcitonin resulted in a significant
      increase of vertebral bone mineral density to 0.80 +/- 0.09 g/cm2 (p < 0.015).
      Femoral bone mineral density also significantly increased after salmon calcitonin
      therapy to 0.64 +/- 0.11 g/cm2 (p < 0.05). CONCLUSION: These results show that
      calcium and salmon calcitonin increase bone mineral density in male patients with
      osteoporosis. Calcium and calcitonin may be useful in the treatment of male
      osteoporosis; however, further studies are necessary before definite
      recommendations can be made.

PMID- 9163890
TI  - Intracellular pH-measurements in rat duodenal mucosa in vitro using confocal
      laserscan microscopy.
AB  - An improved technique was developed to measure intracellular pH-changes in in
      vitro duodenal mucosa. A confocal laserscan microscope was equipped with a second
      laser to permit dual wavelength excitation measurements employing BCECF (2'7'-bis
      2-carboxyethyl-5-(and-6)carboxyfluorescein), a pH-sensitive fluorescent dye.
      Intact rat duodenal epithelium was mounted in a microperfusion chamber and loaded
      with BCECF via submucosal injection. Viability of the epithelial cells could be
      directly monitored by estimating the nucleus-to-cytoplasm ratio of the
      fluorescence intensity of BCECF. A calibration procedure using isolated duodenal
      cells, allowed estimation of the apparent intracellular pH. Initial apparent
      intracellular pH was 7.32 +/- 0.12, identical to that of isolated duodenocytes.
      Exposure of the duodenal epithelium to 60 mM NH4Cl led to a steady increase in
      apparent intracellular pH of 0.46 units within 2 min. Luminal application of 0.01
      N HCl led to a steady decrease in apparent intracellular pH of 0.53 pH units
      within 1 min and was followed by a slow increase to baseline level after acid
      removal. Thus, confocal laserscan microscopy in combination with BCECF allowed
      noninvasive monitoring of intracellular pH-changes in single cells of an intact
      duodenal epithelium.

PMID- 9163889
TI  - Recurrent hepatitis C virus infection after liver transplantation--long-term
      follow-up with respect to the HCV genotypes/subtypes.
AB  - BACKGROUND/AIMS: Various factors may affect the postoperative course in recurrent
      hepatitis C virus (HCV) infection after liver transplantation (OLT). The aim of
      our study was to evaluate the potential role of HCV genotypes and
      immunosuppressive treatment. METHODS: 17 liver allograft recipients, HCV-RNA
      positive prior to OLT, were followed 26-102 months postoperatively. The diagnosis
      of HCV infection was based on clinical, serological and histological findings and
      detectable HCV-RNA in serum. The genotypes/subtypes were evaluated by a "reverse
      line probe" assay. RESULTS: After OLT hepatitis C viremia was evident in 16 of 17
      allograft recipients (94%). Two patients acquired HCV infection after
      transplantation (incidence 0.84%). Clinically eight of 18 viremic patients
      remained asymptomatic. Ten of 18 had an acute hepatitis (eleven to 27 weeks after
      OLT), of those nine patients developed chronic hepatitis (hepatic activity
      indices: grade 1-3) with progression to fibrosis in two patients. One patient
      subsequently developed cirrhosis. Subtype 1 b was predominant (eleven of 18
      patients). After transplantation subtype 1 b was not associated with a higher
      rate of recurrent hepatitis compared to other genotypes/subtypes (45% in type 1 b
      vs. 71% in type "non-1 b"; n.s.). CONCLUSION: Identical HCV genotypes/subtypes
      before and after OLT indicate a recurrent rather than a postoperatively acquired
      HCV infection of the allograft. Despite viremia most patients had no or mild to
      moderate hepatitis in the long-term follow-up. Different HCV genotypes were not
      associated with specific clinical courses of recurrent HCV infection after OLT.

PMID- 9163891
TI  - Gastrointestinal lymphonodular hyperplasia and lymphoid polyps of the rectum--a
      rare coincidence.
AB  - Lymphoid polyps of the rectum are rare lesions. We report on an 8 1/2-year-old
      boy, who presented with hematochezia and abdominal pain. Flexible endoscopy
      revealed large sessile polyps of the rectum and lymphonodular hyperplasia of the
      duodenum, terminal ileum und descending colon. One rectal polyp was excised in
      toto, microscopically it revealed the typical features of a lymphoid polyp. Based
      on the distinct follicular architecture, the cytomorphology and the
      immunohistochemical findings of the lymphatic infiltrate we were able to
      distinguish this lesion from malignant lymphoma. The coincidence of lymphoid
      polyps and gastrointestinal lymphonodular hyperplasia gives evidence that both
      entities are different variations of the same benign lymphoproliferative process.
      Lymphoid polyps of the rectum should be treated by local excision for diagnostic
      purposes. Immunohistochemical staining of fresh, nonfixed tissue is a useful
      ancillary technique in distinguishing these benign lesions from lymphoma of
      mucosa associated lymphoid tissue (MALT-lymphoma).

PMID- 9163892
TI  - Fractionation and characterization of 4-sulfobutyl ether derivatives of
      cyclomaltoheptaose (beta-cyclodextrin).
AB  - 4-Sulfobutyl ether derivatives of cyclomaltoheptaose (beta-cyclodextrin) (SBE
      beta-CD) are being developed as parenterally safe solubilizing and stabilizing
      agents. SBE-beta-CDs are a mixture of positional and regional isomers containing
      from one to as many as twelve sulfobutyl ether (SBE) groups per cyclodextrin.
      Capillary electrophoretic (CE) analysis of these mixtures resolves these isomers
      based on the molar degree of SBE substitution (ds), and the electropherogram
      shows an almost symmetrical distribution of SBE incorporation centered around the
      band which represents the apparent average degree of substitution for the
      mixture. The objectives of this study were to isolate the different substitution
      bands for their characterization and to evaluate their mass contribution to the
      mixture. Mixtures of SBE-beta-CDs containing from mono- up to deca-SBE
      substitutions were fractionated by preparative anion-exchange chromatography with
      salt concentration gradient elution. The bands for each ds were well resolved as
      characterized by CE analysis with indirect UV detection. The isolated materials
      were desalted and lyophilized to obtain white solids, which were then
      characterized by nuclear magnetic resonance (1H NMR) spectroscopy, capillary
      electrophoresis (CE), and fast-atom-bombardment mass spectrometry (FABMS). The CE
      molar response factor of each ds was then determined, and the actual percent mass
      composition of a SBE-beta-CD mixture was calculated.

PMID- 9163893
TI  - Isolation and characterization by NMR spectroscopy of three monosubstituted 4
      sulfobutyl ether derivatives of cyclomaltoheptaose (beta-cyclodextrin).
AB  - The substitution profile of 4-sulfobutyl ether derivatives of cyclomaltoheptaose
      (beta-cyclodextrin) (SBE-beta-CD) prepared in our laboratories has been
      previously described. However, in those studies, no attempt was made to
      characterize the positional or regional isomers of this material. SBE-beta-CD
      derivatives with degrees of substitution of two or higher represent a large
      number of possible isomers dependent on this positional and regional
      substitution. The monosubstituted SBE derivative, however, cannot have regional
      isomers and, therefore, has only three possible substitution products related to
      the 2-, 3-, and 6-hydroxyl groups of a glucose unit. In this study the isomers
      were fractionated by preparative anion-exchange chromatography with the progress
      of the elution being followed by a capillary electrophoretic (CE) method that
      resolved these isomers. The eluent containing the isomers was processed, and the
      pure materials were characterized by nuclear magnetic resonance spectroscopy (1H
      NMR, DEPT, HETCOR, HOHAHA). Through this analysis the assignment of the
      positional isomers was made.

PMID- 9163894
TI  - Structure of the capsular polysaccharide of Clostridium perfringens Hobbs 5 as
      determined by NMR spectroscopy.
AB  - The complete primary structure of the capsular polysaccharide of Clostridium
      perfringens Hobbs 5, an anaerobic bacterium implicated in food poisoning, was
      determined. The polysaccharide was isolated from C. perfringens Hobbs 5 cells,
      after deproteination, by ethanol precipitation and by ion-exchange
      chromatography. The polysaccharide was comprised of glucose, galactose, mannose,
      N-acetylglucosamine, N-acetylgalactosamine, and glucuronic acid, in equimolar
      ratios. Sequence and linkage assignments of the glycosyl residues were obtained
      by NMR spectroscopy, specifically by the combination of two-dimensional
      homonuclear TOCSY and NOESY experiments and heteronuclear (1H, 13C) multiple
      quantum coherence (HMQC, HMQC-COSY, HMQC-TOCSY and HMBC) experiments. Thus, the
      envelope polysaccharide of C. perfringens Hobbs 5 was found to be a polymer
      composed of a hexasaccharide repeating unit with the following structure:
      [formula: see text] This structure is novel among bacterial cell-surface
      polysaccharides, and it is the first of many serotypically distinct capsular
      polysaccharides of C. perfringens to be described.

PMID- 9163895
TI  - Synthesis of colitose-containing oligosaccharide structures found in
      polysaccharides from Vibrio cholerae O139 synonym Bengal using thioglycoside
      donors.
AB  - The syntheses of the two colitose-containing trisaccharides 8
      methoxycarbonyloctyl (3,6-dideoxy-alpha-L-xylo-hexopyranosyl)-(1-->2)-beta-D
      galactopyranosyl -(1-->3)-2-acetamido-2-deoxy-beta-D-glucopyranoside and 8
      methoxycarbonyloctyl beta-D-galactopyranosyl-(1-->3)-[(3,6- dideoxy-alpha-L-xylo
      hexopyranosyl)-(1-->4)]-2-acetamido-2-deoxy-beta-D- glucopyranoside, and
      tetrasaccharide 8-methoxycarbonyloctyl (3,6-dideoxy-alpha-L-xylo-hexopyranosyl)
      (1-->2)-beta-D-galactopyranosyl - (1-->3)-[(3,6-dideoxy-alpha-L-xylo
      hexopyranosyl)-(1-->4)]-2-acetamido-2 -deoxy- beta-D-glucopyranoside are
      described. The oligosaccharides correspond to structures found in the capsular
      polysaccharide and the lipopolysaccharide of Vibrio cholerae O139 and also to
      lipopolysaccharide structures of E. coli O55 and Salmonella greenside. The
      colitose residues were introduced via dimethyl(methylthio)sulfonium
      trifluoromethanesulfonate promoted glycosylations using colitose thioglycosides
      as glycosyl donors.

PMID- 9163896
TI  - Synthesis of two analogues of the Sda determinant. Replacement of the sialic acid
      residue by a sulfate or a carboxymethyl group.
AB  - Two analogues of the Sda determinant tetrasaccharide have been synthesized in
      order to investigate the physiological role of this carbohydrate moiety. These
      saccharides, having two different anionic substitutes for the sialic acid
      residue, are: beta-D-GalpNAc-(1-->4)-3-O-SO3 H- beta-D-Galp-(1-->4)-beta-D
      GlcpNAc-(1-->O)(CH2)5NH2 and beta-D-GalpNAc-(1-->4)-3-O- COOH-beta-D-Galp-(1-->4)
      beta-D-GlcpNAc-(1-->O)(CH2)5NH2. 5-Azidopentyl (2,6-di-O- benzyl-beta-D
      galactopyranosyl)-(1-->4)-3,6-di-O-benzyl-2-deoxy-2- phthalimido-beta-D
      glucopyranoside served as a general building block. The trisaccharides were
      obtained after prior selective derivatization of HO-3' of the disaccharide
      derivative via a dibutyltin oxide mediated reaction, followed by coupling at HO
      4' with 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-beta-D-galactopyranosyl
      trichloroacetimidate, and processing of the formed trisaccharide derivatives into
      their free forms.

PMID- 9163897
TI  - Synthesis of the Sda determinant and two analogous tetrasaccharides.
AB  - To contribute to the possibility of studying in greater detail the biological
      significance of Sda-containing glycans as occur in Tamm-Horsfall glycoprotein,
      the following three spacer-linked tetrasaccharides have been synthesized: the Sda
      determinant alpha-Neu p5Ac-(2-->3)-[beta- D-GalpNAc-(1-->4)]-beta-D-Galp-(1-->4)
      beta-D-GlcpNAc-(1-->O)(CH2)5NH 2 (1), the Gal-analogue alpha-Neup5Ac-(2-->3)
      [beta-D-Galp-(1-->4)]-beta-D-Galp-(1-->4) -beta-D-GlcpNAc-(1-->O)(CH2)5NH2 (2),
      and the GlcNAc-analogue alpha-Neup5Ac-(2-->3)-[beta-D-GlcpNAc-(1-->4)]- beta-D
      Galp-(1-->4)-beta-D-GlcpNAc-(1-->O)(CH2)5NH2 (3). The general trisaccharide
      acceptor 5-azidopentyl (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy- D
      glycero-alpha-D-galactonon-2-ulopyranosylonate)-(2-->3)-(2 ,6-di-O-benzyl- beta-D
      galactopyranosyl)-(1-->4)-3,6-di-O- benzyl-2-deoxy-2-phthalimido-beta-D
      glucopyranoside was prepared, using methyl (phenyl 5- acetamido-4,7,8,9-tetra-O
      acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto- non- 2-ulopyranosid)- onate as the
      sialyl donor. For the syntheses of 1, 2, and 3 the glycosyl donors 3,4,6-tri-O-
      acetyl-2-deoxy-2-phthalimido-alpha-D-galactopyranosyl bromide, 2,3,4,6-tetra-O
      acetyl-alpha-D- galactopyranosyl bromide, and 3,4,6-tri-O-acetyl-2-deoxy-2
      phthalimido -beta-D-glucopyranosyl trichloroacetimidate, respectively, proved to
      be the most suitable.

PMID- 9163898
TI  - Structural analysis of the capsular antigen of Escherichia coli O8:K41:H11.
AB  - The primary structure of the acidic capsular antigen of Escherichia coli
      O8:K41:H11 was shown by monosaccharide analysis, methylation analysis, and by 1D
      and 2D (1)H amd (13)C NMR spectroscopy to be composed of branched pentasaccharide
      repeating units with the structure (formula: see text)

PMID- 9163899
TI  - The application of various protic acids in the extraction of (1-->3)-beta-D
      glucan from Saccharomyces cerevisiae.
AB  - Glucans are (1-->3)-beta-linked glucose polymers which have immune-stimulating
      capability. The extraction of water-insoluble (1-->3)-beta-D-glucan form
      Saccharomyces cerevisiae employs hydrochloric acid. Hydrochloric acid is
      difficult to employ in the large-scale pharmaceutical extraction of glucans due
      to its corrosive nature and toxicity. To address these concerns, we determined
      whether acetic, formic or phosphoric acid can be substituted for hydrochloric
      acid in the process for the isolation of (1-->3)-beta-D-glucan. The resulting
      microparticulate glucans were employed as the starting material for the
      production of (1-->3)-beta-D-glucan phosphate. 13C NMR analysis of the glucan
      phosphates derived from the acetic, formic or phosphoric acid-extracted
      microparticulate glucan show excellent correspondence to hydrochloric acid
      extracted glucan and laminarin, a (1-->3)-beta-D-glucan standard, indicating that
      the primary structure is not altered by the acid used for extraction. Glucan
      phosphate prepared from hydrochloric acid had a Mw of 7.2 x 10(4) g/mol, rmsz of
      17.7 nm, of 1.50 and (eta) of 49.0 mL/g. Glucan phosphate prepared from acetic
      acid had a primary polymer peak with a Mw of 1.4 x 10(6) g/mol, rmsz of 23.6 nm,
      I of 1.93 and (eta) of 62.4 mL/g. Glucan phosphate prepared from formic acid had
      a main polymer peak with a Mw of 1.2 x 10(6) g/mol, rmsz 27.1 nm, I of 1.56 and
      (eta) of 89.0 mL/g. Glucan phosphate prepared from phosphoric acid had a primary
      polymer peak with a Mw of 6.6 x 10(5) g/mol, rmsz of 32.3 nm, I of 2.70 and (eta)
      of 91.3 mL/g. These data indicate that the molecular mass, size, polydispersity
      and intrinsic viscosity of the glucan phosphate obtained is influenced by the pKa
      of protic acid employed to extract the microparticulate glucan. However, the
      primary structure and side-chain branching are not substantially altered
      regardless of the acid employed.

PMID- 9163900
TI  - Rapid distinction between Leptospira interrogans and Leptospira biflexa by PCR
      amplification of 23S ribosomal DNA.
AB  - Bacterial specific primers were used to amplify 23S rRNA genes from a
      representative strain from each of the 23 serogroups of the pathogenic Leptospira
      interrogans and 8 strains from 6 serogroups of the non-pathogenic Leptospira
      biflexa. Only regions of extreme variability, which had been identified on the
      basis of homology-based search of all the 23S rRNA sequences available in GenBank
      database, were sequenced from the amplified products. PCR primers that had the
      potential to distinguish L. interrogans from L. biflexa species were designed
      from the derived sequences and a sensitive PCR protocol developed. The PCR method
      enabled the differentiation of the 59 strains of the 23 serogroups of L.
      interrogans from the 8 strains of 6 serogroups of L. biflexa. Further
      investigation by 16S rDNA sequencing of two strains of L. interrogans, which gave
      unexpected PCR results, provided evidence that they had been misclassified and
      hence we propose to reassign them to L. biflexa.

PMID- 9163901
TI  - Elemental iron does repress transferrin, haemopexin and haemoglobin receptor
      expression in Haemophilus influenzae.
AB  - The iron repressible nature of Haemophilus influenzae transferrin binding
      proteins suggests a regulatory role for elemental iron in their expression. The
      existence of a Haemophilus ferric uptake repressor (Fur) binding motif identified
      in the promoter region of both tbpA and tbpB further supports this hypothesis.
      However, a recent study using brain heart infusion growth medium suggested that
      transferrin binding protein synthesis in H. influenzae was haem-rather than iron
      regulated. The present study re-investigates this observation and using a
      chemically defined medium, we demonstrate that elemental iron haem or
      protoporphyrin IX can each regulate Haemophilus influenzae transferrin,
      haemopexin and haemoglobin receptor expression.

PMID- 9163902
TI  - Genetic relationship among isolates of Helicobacter pylori: evidence for the
      existence of a Helicobacter pylori species-complex.
AB  - We investigated the population genetics of 23 isolates of H. pylori by allozyme
      electrophoresis using 16 enzyme loci. Isolates were obtained from adult patients
      of whom 48% were of Greek extraction. Eight patients (35%) had an active duodenal
      ulcer. Allelic variation per loci ranged from 2 to 11 alleles. Four major genetic
      clusters were apparent, having > 75% fixed genetic differences. There was no
      distinct clustering (clonal structure) on the basis of the geographical origin of
      the persons from whom isolates were obtained, indicating that this bacterium has
      not recently jumped a species barrier into humans. Isolates associated with ulcer
      disease were not monophyletic, with isolates from ulcer patients being found in
      phylogenetically diverse branches of the dendogram derived from the data. Based
      on the genetic diversity of H. pylori isolates, we propose that isolates should
      be classified as belonging not to a single species but to a 'Helicobacter pylori
      species-complex'.

PMID- 9163903
TI  - Molecular cloning and expression studies of two divergent alpha-tubulin genes in
      Neurospora crassa.
AB  - Three alpha-tubulin isoforms were previously detected in Neurospora crassa. We
      have cloned and analysed two alpha-tubulin cDNAs, Tub alpha A and Tub alpha B
      that encode polypeptides of 453 and 451 amino acids, respectively. The encoded
      amino acids exhibit an unusual divergence of 35%. This is the highest divergence
      ever observed between alpha-tubulins from the same species. The expression of the
      two genes is developmentally regulated. We did not detect any transcription of
      the Tub alpha A gene in dormant macroconidia and during the first 30 min of
      development even though the alpha-tub A protein is already present in the early
      stage of germination. In contrast, the Tub alpha B gene is continuously
      transcribed during the vegetative cycle and the expression profile of the protein
      follows the ones of its mRNA.

PMID- 9163904
TI  - Inhibition of ergosterol biosynthesis is not accompanied by a change in fatty
      acid composition in Saccharomyces cerevisiae treated with the antifungal agent 6
      amino-2-n-pentylthiobenzothiazole.
AB  - The antifungal agent 6-amino-2-n-pentylthiobenzothiazole at a concentration of 40
      microM lowered the specific growth rate of exponentially growing cultures of
      Saccharomyces cerevisiae by 36%. Treatment with 6-amino-2-n
      pentylthiobenzothiazole inhibited the biosynthesis of ergosterol and caused an
      accumulation of the methylated sterol precursors ergosta-5,7-dienol and squalene,
      but had no significant effect on the composition and the rate of biosynthesis of
      fatty acids. The results indicate that neither the inhibition of ergosterol
      biosynthesis, nor the slowing-down of culture growth by this antifungal agent,
      led to a compensatory alteration in the pattern of fatty-acyl chains in membrane
      lipids. This finding contradicts the accepted wisdom for the action of a number
      of antifungal agents.

PMID- 9163906
TI  - Identification of Saccharomyces cerevisiae GLY1 as a threonine aldolase: a key
      enzyme in glycine biosynthesis.
AB  - Determination of enzyme-specific activities revealed that GLY1 encodes a
      threonine aldolase (TA) in Saccharomyces cerevisiae. A knock-out mutant
      auxotrophic for glycine lacked detectable activity. After transformation with
      YEp24GLY1 glycine prototrophy was restored and TA-specific activity was 16-fold
      higher than in the wild type. Growth experiments using glucose as the sole carbon
      source showed that GLY1 is more important for glycine biosynthesis than SHM1 and
      SHM2 encoding alternative serine hydroxymethyltransferases. On ethanol as carbon
      source simultaneous disruption of GLY1, SHM1 and SHM2 did not lead to glycine
      auxotrophy because glycine biosynthesis proceeds via alanine glyoxylate
      aminotransferase.

PMID- 9163905
TI  - Integrative vector for constructing single-copy translational fusions between
      regulatory regions of Bacillus subtilis and the bgaB reporter gene encoding a
      heat-stable beta-galactosidase.
AB  - Here we report on the construction of two integrative plasmids for Bacillus
      subtilis allowing in vitro construction of translational fusions. Both plasmids
      contain two cassettes in tandem: the bgaB gene encoding a heat-stable beta
      galactosidase devoid of its own regulatory sequences and the first two codons
      followed by a neomycin-resistance gene for selection in B. subtilis. Both
      cassettes are flanked by the 3'- and 5'-end of the amyE gene (encoding alpha
      amylase) allowing integration of both cassettes at the amyE locus of the B.
      subtilis chromosome. For propagation in Escherichia coli, the plasmids contain
      the pBR322 origin of DNA replication and the beta-lactamase-encoding gene.
      Whereas one vector needs a promoter, a Shine-Dalgarno sequence and the beginning
      of a gene fused in-frame to bgaB, the other one already carries a constitutive
      promoter. The versatility of the gene fusion vectors was demonstrated by the
      integration of the regulatory regions of the dnaK and the cat-86 genes. In the
      first case, heat-inducible expression was found, and by comparison with an operon
      fusion, it seems that the dnaK operon is regulated at both the transcriptional
      and the posttranscriptional level. In the second case, chloramphenicol-inducible
      regulation of the gene fusion could be demonstrated.

PMID- 9163907
TI  - Identification of a lactoferrin-binding protein in Prevotella nigrescens.
AB  - A 40-kDa lactoferrin-binding protein was identified in a strain of Prevotella
      nigrescens isolated from a patient with periodontitis. The protein was purified
      by affinity column chromatography using a Sepharose-lactoferrin column and
      detergent-solubilized membranes. The N-terminal sequence revealed no apparent
      similarities with any other sequenced bacterial protein. The native conformation
      of the 40-kDa protein was a condition to bind either iron-free or iron-saturated
      lactoferrin. A possible function of this Lf-binding protein could be related with
      an iron acquisition mechanism in P. nigrescens.

PMID- 9163908
TI  - A gene encoding a membrane protein exists upstream of the amoA/amoB genes in
      ammonia oxidizing bacteria: a third member of the amo operon?
AB  - The gene cluster encoding ammonia monooxygenase (AMO) in the chemolithotrophic
      soil bacterium Nitrosospira sp. NpAV was found to contain a third open reading
      frame, termed amoC, upstream of the genes amoA and amoB that encode the subunits
      of AMO. The amoC gene and its flanking regions were isolated and sequenced from a
      4.4 kb EcoRI fragment that contains one of three copies of the ammonia
      monooxygenase gene cluster. The presence of this gene upstream of the other two
      amoA gene copies in Nitrosospira NpAV as well as upstream of amoA genes in the
      genomes of other ammonia oxidizing nitrifiers (strains in the genera
      Nitrosomonas, Nitrosopira, Nitrosolobus and Nitrosovibrio) was confirmed using
      genomic DNA, oligodeoxyribonucleotide primers and the PCR. The amoC gene in
      Nitrosospira sp. NpAV encodes a 270 amino acid polypeptide of approximately 36
      kDa. Topological analysis of the predicted primary structure revealed 6 membrane
      spanning domains. The amoC gene was expressed in recombinant Escherichia coli
      from its indigenous promoter.

PMID- 9163909
TI  - Extracellular DNA from Serpulina hyodysenteriae consists of 6.5 kbp random
      fragments of chromosomal DNA.
AB  - Preparations of chromosomal DNA from a number of Serpulina hyodysenteriae strains
      have shown, using agarose gel electrophoresis, the presence of an additional band
      with a mobility similar to that of a 6.5 kbp linear DNA fragment. Analysis showed
      that this is not a plasmid but rather a form of extracellular DNA like that
      observed for Gram-negative bacteria. However, unlike the extracellular DNA from
      Gram-negative bacteria, which showed a similar band profile to that of the DNA
      from whole cells, that from S. hyodysenteriae consisted primarily of fragments of
      a fixed 6.5 kbp.

PMID- 9163910
TI  - Growth inhibition of Prevotella ruminicola by protamine.
AB  - Growth of Prevotella ruminicola strains B(1)4 (subsp. brevis) and D31d (subsp.
      ruminicola), was inhibited by protamine, a polycationic, low molecular mass
      protein. Results showed that protamine has a bacteriocidal effect when present in
      concentrations exceeding 30 micrograms ml-1. Protamine exerted its toxic effects
      by disrupting the outer membrane, which was demonstrated by: (i) an increased
      sensitivity to hydrophobic antibiotics (novobiocin and monensin) and (ii) release
      of the periplasmic enzyme alkaline phosphatase following short-term exposure to
      protamine. Although the concentrations of protamine inhibitory to P. ruminicola
      are relatively low, the effects of such a compound are probably too broad to
      permit its successful use in terms of manipulating ruminal proteolysis.

PMID- 9163911
TI  - Relationship between antibacterial activity and cell surface binding of
      lactoferrin in species of genus Micrococcus.
AB  - Human lactoferrin was bactericidal in vitro for Micrococcus luteus but not for
      other Micrococcus species (M. radiophilus, M. roseus and M. varians). A
      correlation between the binding of lactoferrin to the bacterial surface and the
      antimicrobial action was observed. Viability assays showed that ferric, but not
      ferrous, salts prevented binding and consequently M. luteus was not killed. The
      unsaturated form of lactoferrin showed a greater affinity than that of the iron
      saturated molecule for lipomannan, a lipoglycan present on the cell wall of M.
      luteus, supporting the role for lipomannan as one of the possible binding sites
      of lactoferrin on M. luteus.

PMID- 9163912
TI  - A putative role for calmodulin in the activation of Neurospora crassa chitin
      synthase.
AB  - The possible role of calmodulin in cell wall formation and chitin synthesis was
      studied in Neurospora crassa by examining the effects of anti-calmodulin agents
      on protoplast regeneration and possible associations between chitin synthase and
      calmodulin related proteins in microsomal isolates. Protoplast regeneration was
      inhibited by trifluoperazine (> 20 microM), an anticalmodulin agent. Chitin
      synthase activity in microsomes was associated with that of calmodulin-dependent
      protein kinase and inhibited by trifluoperazine (100 microM). In vitro activity
      of chitin synthase was enhanced upon inclusion of calmodulin (300 ng) in the
      assay mix, 63% over and above the stimulation brought about by trypsin, an
      activator of the enzyme. Autoradiography studies on microsomal proteins revealed
      calmodulin-dependent phosphorylation of two microsomal calmodulin-binding
      proteins (106 and 89 kDa). The results indicate that calmodulin-mediated
      phosphorylation of specific microsomal proteins may be important in the in vivo
      activation of chitin synthase.

PMID- 9163913
TI  - Interactions between Fusobacterium necrophorum hemolysin, erythrocytes and
      erythrocyte membranes.
AB  - The interactions between the hemolysin of Fusobacterium necrophorum subsp.
      necrophorum, erythrocytes and erythrocyte membranes were studied as an attempt to
      determine the initial characteristics leading to hemolysis. The spectrum of
      erythrocyte sensitivity indicated that horse, dog and mouse erythrocytes were
      highly sensitive whereas those of cattle, sheep, goat and chicken were
      insensitive to the hemolysin. Binding of hemolysin to horse and dog erythrocytes
      or their ghosts was more pronounced than to those of cattle and sheep as detected
      by a decrease of hemolytic activity from hemolysin preparations. The kinetics of
      hemolysis revealed that lysis is preceded by a prelytic phase characterized by
      binding of hemolysin to erythrocytes. Treatment of horse erythrocytes with
      hemolysin at various temperatures prior to incubation at 37 degrees C also
      revealed that this binding prelytic phase is temperature independent. This was
      followed by a temperature dependent lytic stage since erythrocytes pretreated
      with hemolysin and incubated at 4 degrees C showed no hemolysis. An inverse
      relation was found between erythrocyte concentration and hemolytic activity
      suggesting a multiple-hit mechanism of hemolysis.

PMID- 9163914
TI  - Differentiation of human and animal strains of Streptococcus dysgalactiae by
      pulsed-field gel electrophoresis.
AB  - The genetic diversity among 54 human isolates and 33 animal isolates belonging to
      the species Streptococcus dysgalactiae (20 alpha-haemolytic Streptococcus
      dysgalactiae, 23 Streptococcus equisimilis, 43 group G streptococci and one group
      L streptococcus) was evaluated by macrorestriction analysis of chromosomal DNA
      with SmaI and resolution by pulsed-field gel electrophoresis. This technique
      revealed a high degree of intraspecies polymorphism, leading to the
      differentiation of 80 distinct banding patterns, and identified the presence of
      two major clusters, one containing isolates of human origin and the other
      isolates of animal origin. These results suggest than human and animal isolates
      of S.dysgalactiae are genetically distinct, and support the recent proposal of
      the subspecies S. dysgalactiae subsp. equisimilis for human isolates. The
      heterogeneity revealed within isolates from the same host type indicates that
      pulsed-field gel electrophoresis is a powerful epidemiological tool for studying
      S. dysgalactiae infections.

PMID- 9163915
TI  - Localization by immunoelectron microscopy of antigens of Chlamydia psittaci
      suitable for diagnosis or vaccine development.
AB  - Two different antigens of serotype 1 Chlamydia psittaci were localized using
      three immunoelectron microscopy techniques: non-embedding, pre-embedding and post
      embedding. The antigens had previously been described as being of potential use
      in diagnosis (80-90 kDa protein region) and vaccine development (110 kDa
      protein). The results show a direct relationship between the protective capacity
      of the antigens and their surface localization on the elementary bodies, which
      are the infectious form of Chlamydia. The 80-90 kDa protein region is located on
      the surface of reticulate bodies but not of elementary bodies, where it was
      located periplasmically, while the 110 kDa protein occurs on the surface of both
      elementary and reticulate bodies.

PMID- 9163916
TI  - Immobilization and ethanol stress induce the same molecular response at the level
      of the cell wall in growing yeast.
AB  - The effect of immobilization on the cell wall of Saccharomyces cerevisiae cells
      was investigated in comparison with freely suspended batch grown cells. The
      pattern of mannoproteins released from the cell wall after Zymolyase digestion
      showed the presence of new mannoprotein species when cell growth takes place in a
      state of immobilization. The same result was obtained by exposure of freely
      suspended cells to a stressful concentration of ethanol, showing that two
      different adverse culture conditions induce a similar molecular response at the
      cell wall level.

PMID- 9163918
TI  - Primary structure analysis and adhesion studies on the major outer membrane
      protein of Campylobacter jejuni.
AB  - The major outer membrane protein of Campylobacter jejuni (MOMP, 43 kDa), supposed
      to be one of the structures responsible for adhesion to INT 407 cells, was
      isolated from the crude outer membrane preparation by treatment with n-octyl-beta
      D-glucopyranoside followed by preparative SDS-polyacrylamide gel electrophoresis.
      By cleavage of the isolated protein with cyanogen bromide and proteolytic
      enzymes, peptides were generated, separated by reverse phase high pressure liquid
      chromatography, and sequenced by automatic Edman degradation. The protein was
      aligned by identification of overlapping peptides. Treatment of bacteria with
      proteinase K prior to preparation of the outer membrane yielded a truncated MOMP
      with an apparent molecular mass of 25 kDa consisting of the C-terminal part of
      the protein. The isolated MOMP was functionally characterized by significant
      binding activity towards INT 407 cell membranes when isolated by preparative
      native gel electrophoresis, however, no binding activity was detected when the
      protein was isolated in the presence of SDS.

PMID- 9163917
TI  - The hupC gene product is a component of the electron transport system for
      hydrogen oxidation in Pseudomonas hydrogenovora.
AB  - The hydrogenase gene cluster containing nine genes (hupSLCDFGHIJ) was identified
      by sequencing of an 8.8-kb DNA region from Pseudomonas hydrogenovora. To
      investigate the function of the hupC gene product, we isolated a hupC-null mutant
      (HID3) of P. hydrogenovora by introducing an in-frame deletion into the hupC. The
      mutant, HID3, could not grow autotrophically but retained half the level of
      hydrogenase activity of the wild-type strain. Results of the oxygen consumption
      test and Western blot analysis revealed that the hupC gene product is a b-type
      cytochrome but not involved in the hydrogenase maturation process.

PMID- 9163919
TI  - Large chromosomal inversions occur in Pseudomonas aeruginosa clone C strains
      isolated from cystic fibrosis patients.
AB  - An analysis of the chromosomal structure of 21 Pseudomonas aeruginosa clone C
      genotypes of various origins was carried out. The circular chromosomes showed
      various insertions and deletions which did not alter the gene order in 6
      environmental and one ear isolate in comparison with strain PAO and strain C.
      However, the chromosome structure differed by at least one large inversion in 50%
      of the genotypes (7/14) isolated from cystic fibrosis patients. Recombination
      endpoints were scattered throughout the chromosome. All but one inversion
      included the terminus of replication which was displaced by the recombination
      events. The rearrangements shifted the positions of the rrn operons with respect
      to the origin of replication, but the transcription of the rrn operons remained
      in the same direction as replication. The exclusive detection of inversions in
      isolates from cystic fibrosis lungs, which represent an atypical habitat for P.
      aeruginosa, supports the theory that peculiar features of this new ecological
      niche may select, cause or tolerate genomic changes.

PMID- 9163920
TI  - Cloning and sequencing of a species-specific nucleotide fragment of Borrelia
      burgdorferi sensu stricto, which is repeated in several plasmids of the species.
AB  - Among the etiological agents of Lyme disease, Borrelia burgdorferi sensu stricto
      strains carry a 16 kb plasmid, which did not hybridize to plasmids of B. garinii
      and B. afzelii strains. A 1271 bp DNA fragment of the 16 kb plasmid was cloned.
      It hybridized to several plasmids of this species (16, 27 and 55 kb). Sequencing
      of the cloned insert revealed a 327 bp ORF coding for a 14 kDa protein of unknown
      function, which could be expressed in E. coli. This ORF, conserved among B.
      burgdorferi sensu stricto strains, was carried by the same three plasmids.

PMID- 9163921
TI  - Yeast linear plasmids with T2AG3 telomeres: TEL+CEN antagonism and genetic and
      molecular stability.
AB  - A linear plasmid containing ARS1, CEN4, and 48 bp of vertebrate (T2AG3) telomeric
      sequences at each end was used to transform Saccharomyces cerevisiae. Only
      circular plasmids that had lost the centromere and had retained the T2AG3
      sequences were obtained, indicating that the vertebrate T2AG3 sequences and the
      yeast CEN4 could not be simultaneously present in this vector. This hypothesis
      was verified by removing the CEN4 sequence from the construct. In fact, the
      resulting transformants contained two classes of efficiently replicating linear
      plasmids: one of the expected size and one about twice as large. During
      subsequent growth, plasmids of the former, but not latter, class were subjected
      to concatemer formation. This can best be explained by recombination events
      involving the T2AG3 sequences at the ends of the molecule, since very similar
      centric and acentric linear plasmids bearing Tetrahymena telomeric ends
      replicated faithfully.

PMID- 9163922
TI  - Erratum to "The methanol oxidation genes mxaFJGIR (S) ACKLD in Methylobacterium
      extorquens" [FEMS Microbiol. Lett. 146 (1997) 31-38].

PMID- 9163923
TI  - Feature-detecting auditory neurons in the brain of a sound-producing fish.
AB  - The mormyrid fish Pollimyrus adspersus has auditory specializations for sound
      pressure detection and uses acoustic displays in its natural social behavior. In
      this paper it is shown that auditory neurons in the mesencephalon (torus
      semicircularis) are activated selectively by temporal features of complex sounds.
      Single neurons were recorded while presenting sounds to fish underwater. The
      stimuli were acoustic click trains, 400 ms in duration, and were synthesized with
      differing inter-click-intervals (ICIs). The natural sounds of this species are
      composed similarly and the range of ICIs synthesized overlapped with the natural
      range (5-40 ms). One-third of the neurons studied were strongly selective for a
      narrow range of ICIs, increasing spike rate by ten fold or more at the best ICI
      compared to the minimum response observed. The best ICI for interval selective
      neurons remained stable when the sound pressure of the stimulus was changed.
      Neurons that were selective gave phasic responses to tone bursts, and most had
      non-monotonic rate level functions. The origin of interval selectivity is
      discussed and a time-based computational mechanism is proposed.

PMID- 9163924
TI  - Sexual dimorphism and species differences in the neurophysiology and morphology
      of the acoustic communication system of two neotropical hylids.
AB  - We examined auditory tuning and the morphology of the anatomical structures
      underlying acoustic communication in female Hyla microcephala and H. ebraccata
      and compared our findings to data from a previous study (Wilczynski et al. 1993)
      in which we showed species differences in the traits that in males relate to
      differences in the species-typical calls. Female species differences in the best
      excitatory frequency (BEF) of the basilar papilla (BP) were similar to the
      differences seen in males, and females had a significantly lower BEF in H.
      ebraccata, but not H. microcephala. In both species, females had lower BP
      thresholds. Snout-vent length, head width, and tympanic membrane diameters were
      sexually dimorphic in both species and larger in females, whereas laryngeal
      components were sexually dimorphic and larger in males. Middle and inner ear
      volumes were not sexually dimorphic. Despite the significant species differences
      in laryngeal morphology seen in males, female larynges are not significantly
      different. Furthermore, the interaction of species and sex differences resulted
      in significantly different degrees of sex dimorphism in the species, particularly
      for the larynx, which is more sexually dimorphic in H. microcephala, and measures
      of body size, which are more dimorphic in H. ebraccata.

PMID- 9163925
TI  - Toxic effects of antimalarial drugs in Paramecium: role of calcium channels.
AB  - The antimalarial drugs, quinacrine, quinine and mefloquine, as well as the
      structurally-similar compound, W-7, inhibit calcium-dependent backward swimming
      and calcium currents in Paramecium calkinsi. These drugs are also toxic to
      paramecia at high concentrations. Therefore, one site of toxic action of the
      drugs may be the calcium channel. To test this hypothesis, the toxicity of the
      antimalarials and W-7 was compared in paramecia with and without calcium
      channels. Since calcium channels are located on the cilia, calcium channels were
      removed from the paramecia by deciliating the cells. Deciliated cells were found
      to be less susceptible to the lethal effects of the antimalarials and W-7 than
      their ciliated counterparts. Moreover, Pawns, mutants of P. tetraurelia that
      possess cilia but lack functional calcium channels, were also less susceptible to
      the antimalarials than wild-type cells. Thus, calcium channels may be one site of
      toxic action of the antimalarial drugs in paramecia and perhaps in other
      protists.

PMID- 9163926
TI  - Multiple excitatory receptor types on individual olfactory neurons: implications
      for coding of mixtures in the spiny lobster.
AB  - The aim of our paper was to investigate whether single olfactory receptor neurons
      (ORNs) of the spiny lobster Panulirus argus functionally express more than one
      type of receptor, examine the consequences of this on coding of mixtures, and
      compare principles of odorant mixture coding by spiny lobsters with that by the
      channel catfish, which has been studied extensively using the same experimental
      and analytical procedures (Caprio et al. 1989; Kang and Caprio 1991). We examined
      responses of individual taurine-sensitive ORNs to binary mixtures of excitatory
      compounds, either competitive agonists (taurine, beta-alanine, hypotaurine) or
      non-competitive agonists (taurine, L-glutamate, ammonium chloride, adenosine-5'
      monophosphate). Responses to mixtures were compared to two indices: mixture
      discrimination index (MDI) and independent component index (ICI). Binary mixtures
      of competitive agonists had MDI values close to 1.0, as expected for competitors.
      Mixtures of non-competitive agonists had ICI values averaging 0.83, indicating
      the effects of the components are not independent. We conclude that individual
      olfactory cells of spiny lobsters can express more than one type of receptor
      mediating excitation, one of which typically has a much higher density or
      affinity, and that spiny lobster and catfish olfactory cells encode mixtures of
      two excitatory agonists using similar rules.

PMID- 9163927
TI  - Directionality of auditory nerve fiber responses to pure tone stimuli in the
      grassfrog, Rana temporaria. I. Spike rate responses.
AB  - We studied the directionality of spike rate responses of auditory nerve fibers of
      the grassfrog, Rana temporaria, to pure tone stimuli. All auditory fibers showed
      spike rate directionality. The strongest directionality was seen at low
      frequencies (200-400 Hz), where the spike rate could change by up to nearly 200
      spikes s-1, with sound direction. At higher frequencies the directional spike
      rate changes were mostly below 100 spikes s-1. In equivalent dB SPL terms
      (calculated using the fibers' rate-intensity curves) the maximum directionalities
      were up to 15 dB at low frequencies and below 10 dB at higher frequencies. Two
      types of directional patterns were observed. At frequencies below 500 Hz
      relatively strong responses were evoked by stimuli from the ipsilateral (+90
      degrees) and contralateral (-90 degrees) directions while the weakest responses
      were evoked by stimuli from frontal (0 degree or +30 degrees) or posterior (-135
      degrees) directions. At frequencies above 800 Hz the strongest responses were
      evoked by stimuli from the ipsilateral direction while gradually weaker responses
      were seen as the sound direction shifted towards the contralateral side. At
      frequencies between 500 and 800 Hz both directional patterns were seen. The
      directionality was highly intensity dependent. No special adaptations for
      localization of conspecific calls were found.

PMID- 9163928
TI  - Directionality of auditory nerve fiber responses to pure tone stimuli in the
      grassfrog, Rana temporaria. II. Spike timing.
AB  - We studied the directionality of spike timing in the responses of single auditory
      nerve fibers of the grass frog, Rana temporaria, to tone burst stimulation. Both
      the latency of the first spike after stimulus onset and the preferred firing
      phase during the stimulus were studied. In addition, the directionality of the
      phase of eardrum vibrations was measured. The response latency showed systematic
      and statistically significant changes with sound direction at both low and high
      frequencies. The latency changes were correlated with response strength (spike
      rate) changes and were probably the result of directional changes in effective
      stimulus intensity. Systematic changes in the preferred firing phase were seen in
      all fibers that showed phaselocking (i.e., at frequencies below 500-700 Hz). The
      mean phase lead for stimulation from the contralateral side was approximately 140
      degrees at 200 Hz and decreased to approximately 100 degrees at 700 Hz. These
      phaseshifts correspond to differences in spike timing of approximately 2 ms and
      0.4 ms respectively. The phaseshifts were nearly independent of stimulus
      intensity. The phase directionality of eardrum vibrations was smaller than that
      of the nerve fibers. Hence, the strong directional phaseshifts shown by the nerve
      fibers probably reflect the directional characteristics of extratympanic
      pathways.

PMID- 9163929
TI  - Discrimination of sinusoidally frequency-modulated sound signals mimicking
      species-specific communication calls in the FM-bat Phyllostomus discolor.
AB  - In the lesser spear-nosed bat, Phyllostomus discolor, maternal directive calls
      are characterized by an individual type of sinusoidal frequency modulation (=
      SFM) pattern. Beside modulation frequency, modulation depth, carrier frequency,
      and number of modulation cycles per call contribute to the mother's vocal
      signature. Since juvenile P. discolor learn to adapt their isolation calls to the
      corresponding call characteristics of the own mother or even to playback of a
      computer-stored directive call, if hand-reared in the absence of conspecifics,
      the bats' auditory system ought to be able to resolve interindividual differences
      in communication call structure. However, quantitative psychoacoustic data on the
      discrimination of SFM signals in this species are not available. Thus, in the
      present study, lesser spear-nosed bats were trained in a two-alternative forced
      choice procedure to discriminate between two alternatingly presented SFM sound
      signals differing in modulation frequency. Other characteristics of acoustic
      stimuli were identical and designed to mimick the fundamental of species-specific
      calls. By gradually reducing the difference in modulation frequency between both
      stimuli within the behavioural relevant range until the animals' performance
      dropped below the 75%-correct level, a considerable auditory spectro-temporal
      resolution has been revealed. Particularly in comparison to the overall
      interindividual variation of this call parameter (minimal modulation frequency =
      49 Hz, maximum = 100 Hz), the determined average difference limen for modulation
      frequency of 2.42 +/- 0.29 Hz seems substantial and sufficient for labelling
      individuals.

PMID- 9163930
TI  - c-fos expression in the putative avian suprachiasmatic nucleus.
AB  - c-fos induction was investigated as a potential component in the avian photic
      entrainment pathway and as a possible means of locating the central pacemaker in
      birds. In both quail (Coturnix coturnix japonica) and starlings (Sturnus
      vulgaris) exposure to 1 h of light induced Fos-lir in the visual suprachiasmatic
      nucleus but not in the medial suprachiasmatic nucleus. However, the degree of c
      fos induction in the visual suprachiasmatic nucleus was similar at different
      circadian times despite the fact that the light pulses caused differential phase
      shifts in the locomotor rhythm. For golden hamsters the same experiment resulted
      in significantly different levels of Fos-lir in the suprachiasmatic nucleus, as
      well as different phase shifts. Starlings and hamsters were also entrained to T
      cycles that caused a large daily phase shift (T = 21.5 h in starlings, T = 22.67
      hours in hamsters), or no daily phase shift (T = free running period). No
      difference in the induced levels of Fos-lir in the visual suprachiasmatic nucleus
      region was observed between the two groups of starlings, but in hamsters there
      were significantly different levels of Fos-lir in the suprachiasmatic nucleus
      between the two groups.

PMID- 9163931
TI  - Young chickens learn to localize the centre of a spatial environment.
AB  - Young chickens were trained to find food by ground-scratching in the centre of a
      closed uniform arena and were then tested in arenas of similar areas but of
      different shapes. Chickens showed localized searching behaviour in the square
      shaped arena, and maintained this behaviour when placed in a circular or
      triangular (both equilateral and isosceles) arena. With a rectangular-shaped
      arena, obtained by doubling the original square-shaped one, chickens showed more
      dispersed searching along the major axis, but searching tended to be concentrated
      around the centres of the composing squares and around the centre of the
      rectangle itself. When trained in a square- or triangle-shaped arena and then
      tested in an arena of the same shape but a larger area, chickens displayed
      searching behaviour at two different distances from the wall of the arena, one
      corresponding to the correct distance (i.e. centre) in the smaller (training)
      arena, the other to the actual centre of the test arena. On the other hand, in a
      circular arena, chickens searched mainly at a distance midway between the radius
      of the small (training) and of the large (testing) circular arena. These results
      suggest that, during training, chickens encoded information on both the absolute
      and the relative distance of the food from the walls of the arena, the latter
      information being more accurate when the arena displayed identifiable features
      such as corners.

PMID- 9163933
TI  - Emotion, motivation, and text comprehension: the detection of contradictions in
      passages.
AB  - The authors investigated the effects of experimentally induced mood states on the
      identification of contradictions in text passages and ratings of comprehension in
      3 experiments. Mood impaired comprehension in college students across a variety
      of passages, as evidenced by a depressive impairment in contradiction
      identification and an increased number of false identifications among depressed
      participants. Additionally, depressed individuals were less accurate in their
      judgments of passage difficulty. These findings are consistent with the resource
      allocation model of mood effects, which attributes impaired comprehension to the
      activation of intrusive, irrelevant thoughts during reading of the passage. It is
      further argued that these results cannot be explained simply by a deficit in
      motivation of the depressed participants.

PMID- 9163932
TI  - On the nature and scope of featural representations of word meaning.
AB  - Behavioral experiments and a connectionist model were used to explore the use of
      featural representations in the computation of word meaning. The research focused
      on the role of correlations among features, and differences between speeded and
      untimed tasks with respect to the use of featural information. The results
      indicate that featural representations are used in the initial computation of
      word meaning (as in an attractor network), patterns of feature correlations
      differ between artifacts and living things, and the degree to which features are
      intercorrelated plays an important role in the organization of semantic memory.
      The studies also suggest that it may be possible to predict semantic priming
      effects from independently motivated featural theories of semantic relatedness.
      Implications for related behavioral phenomena such as the semantic impairments
      associated with Alzheimer's disease (AD) are discussed.

PMID- 9163934
TI  - Uncertain responses by humans and rhesus monkeys (Macaca mulatta) in a
      psychophysical same-different task.
AB  - The authors asked whether animals, like humans, use an uncertain response
      adaptively to escape indeterminate stimulus relations. Humans and monkeys were
      placed in a same-different task, known to be challenging for animals. Its
      difficulty was increased further by reducing the size of the stimulus
      differences, thereby making many same and different trials difficult to tell
      apart. Monkeys do escape selectively from these threshold trials, even while
      coping with 7 absolute stimulus levels concurrently. Monkeys even adjust their
      response strategies on short time scales according to the local task conditions.
      Signal-detection and optimality analyses confirm the similarity of humans' and
      animals' performances. Whereas associative interpretations account poorly for
      these results, an intuitive uncertainty construct does so easily. The authors
      discuss the cognitive processes that allow uncertainty's adaptive use and
      recommend further comparative studies of metacognition.

PMID- 9163936
TI  - Meal patterns of cats encountering variable food procurement cost.
AB  - The meal patterns of 2 cats in a laboratory habitat with variable foraging costs
      were examined in a foraging paradigm in which subjects could initiate meals at
      any time by completing a predetermined number of bar presses (the procurement
      price) and then could eat any amount. From meal to meal, the procurement price
      either was fixed or varied among a geometric series of five prices. As the fixed
      price or the mean of the variable prices increased, meal frequency decreased and
      meal size increased; daily intake was unaffected. Within variable-price
      schedules, meal size was not related to the just-paid procurement price. These
      results suggest that cats respond to the global rather than to the local cost
      structure of their habitat. They appear to respond to an average of the prices
      encountered, initiating meals of a frequency and size appropriate to that
      average. This was true even when the average price was high, meals were
      infrequent, and thus price encounters were widely separated in time. Therefore,
      the time window over which the consequences of behavior can affect behavior is
      longer than often conceived, at least in economies in which the animal controls
      its intake and the frequency, size, and distribution of its meals.

PMID- 9163935
TI  - A transformation of respondently conditioned stimulus function in accordance with
      arbitrarily applicable relations.
AB  - Adult male subjects saw a sexual film clip paired with a nonsense syllable (C1).
      Similarly, an emotionally neutral film clip was paired with a second nonsense
      syllable (C3). Responses to the nonsense syllables were recorded as skin
      resistance responses. Subjects were also trained in a series of related
      conditional discriminations, using the C1 and C3 stimuli, from which the
      following equivalence relations were predicted; A1-B1-C1, A2-B2-C2, and A3-B3-C3.
      Some subjects were given matching-to-sample (equivalence) tests after the
      conditional discrimination training (Experiment 1), whereas others were not
      (Experiment 2). Subjects were tested for a transformation of eliciting functions
      by presenting the A1 and A3 stimuli, which were related through equivalence to C1
      and C3, respectively. Five of the 6 subjects who showed significantly greater
      conditioned responses to C1 than to C3, also showed significantly greater skin
      resistance responses to A1 than to A3. Two additional subjects demonstrated a
      transformation of an eliciting stimulus function in accordance with five-member
      equivalence relations (Experiment 3), and another 5 subjects demonstrated similar
      effects in accordance with the relations of sameness and opposition (Experiment
      4).

PMID- 9163937
TI  - Memory processes in delayed spatial discriminations: response intentions or
      response mediation?
AB  - Pigeons were trained on a pair-comparison task in which left versus right choices
      were reinforced following different sequences of two center-key stimuli. Choice
      accuracy was higher when retention intervals occurred after the entire sequence
      than when they separated the two stimuli comprising it, and this effect occurred
      independently of whether the initial and terminal stimuli came from the same or
      different dimensions. The initial stimulus from the prior trial was a source of
      proactive interference only in groups for which the retention interval separated
      the two sequence stimuli. By contrast, differential delay-interval behavior was
      observed only in groups for which the retention interval followed presentation of
      the entire sequence. These results indicate that coding processes in delayed
      discriminations are influenced by the location of the retention interval, and
      that response mediation affects retention performances if the reinforced choice
      can be determined prior to the interval.

PMID- 9163938
TI  - Running and responding reinforced by the opportunity to run: effect of reinforcer
      duration.
AB  - The present study investigated the effect of reinforcer duration on running and
      on responding reinforced by the opportunity to run. Eleven male Wistar rats
      responded on levers for the opportunity to run in a running wheel. Opportunities
      to run were programmed to occur on a tandem fixed-ratio 1 variable-interval 30-s
      reinforcement schedule. Reinforcer duration varied across conditions from 30 to
      120 s. As reinforcer duration increased, the rates of running and lever pressing
      declined, and latency to lever press increased. The increase in latency to
      respond was consistent with findings that unconditioned inhibitory aftereffects
      of reinforcement increase with reinforcer magnitude. The decrease in local lever
      pressing rates, however, was inconsistent with the view that response strength
      increases with the duration of the reinforcer. Response rate varied inversely,
      not directly, with reinforcer duration. Furthermore, within-session data
      challenge satiation, fatigue, and response deprivation as determinants of the
      observed changes in running and responding. In sum, the results point to the need
      for further research with nonappetitive forms of reinforcement.

PMID- 9163939
TI  - Determination of discount functions in rats with an adjusting-amount procedure.
AB  - An adjusting-amount procedure was used to measure discounting of reinforcer value
      by delay. Eight rats chose between a varying amount of immediate water and a
      fixed amount of water given after a delay. The amount of immediate water was
      systematically adjusted as a function of the rats' previous choices. This
      procedure was used to determine the indifference point at which each rat chose
      the immediate amount and the delayed amount with equal frequency. The amount of
      immediate water at this indifference point was used to estimate the value of the
      delayed amount of water. In Experiment 1, the effects of daily changes in the
      delay to the fixed reinforcer (100 microliters of water delivered after 0, 2, 4,
      8, or 16 s) were tested. Under these conditions, the rats reached indifference
      points within the first 30 trials of each 60-trial session. In Experiment 2, the
      effects of water deprivation level on discounting of value by delay were
      assessed. Altering water deprivation level affected the speed of responding but
      did not affect delay discounting. In Experiment 3, the effects of varying the
      magnitude of the delayed water (100, 150, and 200 microliters) were tested. There
      was some tendency for the discounting function to be steeper for larger than for
      smaller reinforcers, although this difference did not reach statistical
      significance. In all three experiments, the obtained discount functions were well
      described by a hyperbolic function. These experiments demonstrate that the
      adjusting-amount procedure provides a useful tool for measuring the discounting
      of reinforcer value by delay.

PMID- 9163940
TI  - Attacking arthritis. New treatments seek to rebalance the immune system.

PMID- 9163941
TI  - Overcoming the obstacles to gene therapy.

PMID- 9163942
TI  - Nonviral strategies for gene therapy.

PMID- 9163943
TI  - Gene therapy for cancer.

PMID- 9163944
TI  - Gene therapy for the nervous system.

PMID- 9163945
TI  - What cloning means for gene therapy.

PMID- 9163946
TI  - Microbial linear plasmids.
AB  - While plasmids were originally considered to be generally circular until almost
      two decades ago, linear elements were reported to exist as well. They are now
      known to be common genetic elements in both, pro- and eukaryotes. Two types of
      linear plasmids exist, the so-called hairpin plasmids with covalently closed ends
      and those with proteins bound to their 5' termini. Hairpin plasmids are common in
      human-pathogenic Borrelia spirochetes, in which they are instrumental in escape
      from the immunological response; cryptic hairpin elements are present in
      mitochondria of the plant pathogenic fungus Rhizoctonia solani. Plasmids with 5'
      attached proteins constitute the largest group. In actinomycetous bacteria they
      are conjugative and usually confer advantageous phenotypes, e.g. formation of
      antibiotics, degradation of xenobiotics, heavy-metal resistance and growth on
      hydrogen as the sole energy source. In contrast, the majority of linear plasmids
      from eukaryotes are cryptic, with only a few exceptions. In some yeasts a killer
      phenotype may be associated, the most thoroughly investigated elements being
      those from Kluyveromyces lactis killer strains. In Neurospora spp. and in
      Podospora anserina, senescence and longevity respectively are correlated with
      linear plasmids. This review focuses on the biology of linear plasmids, their
      environmental significance and their use as tools in molecular and applied
      microbiology.

PMID- 9163947
TI  - D-lysine production from L-lysine by successive chemical racemization and
      microbial asymmetric degradation.
AB  - In order to develop a practical process for D-lysine production from L-lysine,
      successive chemical racemization and microbial asymmetric degradation were
      investigated. The racemization of L-lysine proceeded quantitatively at elevated
      temperatures. A sample of 1000 strains of bacteria, fungi, yeast and actinomyces
      were screened for the ability to degrade L-lysine asymmetrically. Microorganisms
      belonging to the Achromobacter, Agrobacterium, Candida, Comamonas,
      Flavobacterium, Proteus, Providencia, Pseudomonas and Yarrowia genera exhibited a
      high L-lysine-degrading activity. Comamonas testosteroni IAM 1048 was determined
      to be the best strain and used as a biocatalyst for eliminating the L isomer. The
      degradation rate of L-lysine with C. testosteroni IAM 1048 was influenced by pH,
      temperature and agitation speed. Under the optimal conditions, the L isomer in a
      100-g/l mixture of racemic lysine was completely degraded within 72 h, with 47 g
      D-lysine/l left in the reaction mixture. Crystalline D-lysine, with a chemical
      purity greater than 99% and optical purity of 99.9% enantiomeric excess, was
      obtained at a yield of 38% from the reaction mixture by simple purification. An
      engineering analysis of L-lysine racemization and microbial degradation was
      carried out to establish the basis of process design for D-lysine production.

PMID- 9163949
TI  - Functional roles of protein domains on rice alpha-amylase activity.
AB  - Characteristics of two rice alpha-amylases Amy1A and Amy3D, and those of two
      chimeric enzymes Amy1A/3D and Amy3D/1A, engineered from the two isozymes, were
      compared in the light of the functional roles of protein domains in alpha
      amylase. The enzymes that have an Amy1A-type N-terminal domain, Amy1A and
      Amy1A/3D, showed high activity against soluble starch, while the enzymes that
      have an Amy3D-type barrel structure, Amy3D and Amy1A/3D, showed high activity in
      oligosaccharide hydrolysis. Rigidity of protein folding also significantly
      affected the enzyme activity in both soluble starch and oligosaccharide
      hydrolysis. Thus, the present work suggests that the structure of the N-terminal
      domain is important for stability and soluble starch hydrolysis, while the barrel
      structure that forms the active site significantly affects enzyme activities in
      oligosaccharide degradation. We have already characterized two rice alpha-amylase
      isozymes, Amy1A and Amy3D, and a chimeric enzyme engineered from these two
      isozymes, Amy1A/3D (Terashima et al. 1995, 1996a,b). In spite of the high
      homology (70%) of their amino acid sequences, Amy1A and Amy3D showed distinct
      differences in their enzymatic characteristics. The chimeric enzyme Amy1A/3D,
      which consists of an Amy1A-type N-terminal domain and an Amy3D-type barrel
      structure, inherited enzymatic characteristics from the both isozymes. In this
      work, one other chimeric enzyme, Amy3D/1A, which is the counterpart of Amy1A/3D,
      has been characterized. The characteristics of these four enzymes are discussed
      in the light of the functional roles of protein domains.

PMID- 9163948
TI  - Immobilisation of whole bacterial cells for anaerobic biotransformations.
AB  - Anaerobically grown cells of Escherichia coli were immobilised within a range of
      entrapment matrices and packed into a column under standard conditions, and the
      ability of the immobilised cells to reduce nitrite (0.5 mM) was measured at a
      range of flow rates using sodium formate (20 mM) as the electron donor for
      nitrite reduction. A flow-rate/activity plot was constructed for each flow
      through reactor and RA1/2 values (residence time corresponding to 50% nitrite
      removal) calculated for each reactor type. Cells immobilised in flat and hollow
      fibre membranes were the most effective (RA1/2 = 0.35 h and 0.47 h respectively),
      with cells entrapped by dialysis membrane (1.53 h), alginate beads (1.93 h),
      Hypol foam (2.31 h) and polyacrylamide gel (50% nitrite not removed at maximum
      residence time tested: 4.9 h) performing progressively less effectively. Cells
      grown as a biofilm on a range of support materials were also tested in comparable
      packed-bed reactors. Cell loss from these supports was extensive and contributed
      to poor performance of the reactors despite high initial biomass loadings (RA1/2
      values using raschig rings, coke and activated-carbon supports: 1.6 h, 2.3 h and
      1.0 h respectively). Biofilms grown on Pharmacia microcarrier supports and used
      in packed and also fluidised beds were more stable and the performance of these
      reactors was superior to that of biofilm reactors using other supports, and
      comparable to that of the membrane reactors (RA1/2 values for Cytoline 2,
      Cytopore 2 and Cytodex 3: 0.76 h, 0.56 h, 0.68 h respectively).

PMID- 9163950
TI  - Expression of a synthetic protein-based polymer (elastomer) gene in Aspergillus
      nidulans.
AB  - A gene for a synthetic protein-based polymer, G-(VPGVG)119-VPGV, coding for the
      EG-120mer (elastomer), was cloned into a fungal expression vector to allow
      constitutive expression of the polymer controlled by the gpdA (glyceraldehyde-3
      phosphate dehydrogenase) promoter sequence of Aspergillus nidulans. Stable
      transformants of A. nidulans showed plasmid integration with varying copy number
      when analyzed by Southern-blot hybridization. Expression of the synthetic gene
      was demonstrated by Northern-blot hybridization. However, the translational
      efficiency for production of the polymer polypeptide was low, presumably because
      of certain codons in the polymer gene (CCG and GUA) that are rarely used by A.
      nidulans. Partial purification by reversible phase transition followed by sodium
      dodecyl sulfate/polyacrylamide gel electrophoresis revealed the presence of
      polymer protein in a transformant that contained multiple copies of the polymer
      gene. This study represents the first attempt to express a synthetic gene (with
      no natural analog) in a fungus.

PMID- 9163951
TI  - Localization and characterization of inclusion bodies in recombinant Escherichia
      coli cells overproducing penicillin G acylase.
AB  - Various concentrations of isopropyl beta-D-thiogalactopyranoside (IPTG) were used
      to induce production of the enzyme penicillin G acylase by recombinant
      Escherichia coli harboring plasmid pQEA11. The plasmid pQEA11 carries a wild-type
      pga gene, which is under the control of the tac promoter and lacIq. At low IPTG
      concentrations (0.025-0.1 mM), enzyme activity increased with increasing IPTG
      concentrations. At higher IPTG concentrations (0.2 and 0.5 mM), enzyme activity
      declined progressively. Examination of induced recombinant E. coli cells by
      transmission electron microscopy showed the presence of only periplasmic
      inclusion bodies at low IPTG concentrations (up to 0.1 mM) and both periplasmic
      and cytoplasmic inclusion bodies at high IPTG concentrations (0.2 mM and 0.5 mM).
      Results from sodium dodecyl sulfate/polyacrylamide gel electrophoresis and
      immunoblots of whole-cell proteins, membrane proteins and inclusion body proteins
      in these cells indicated that cytoplasmic inclusion bodies constituted an
      accumulation of preproenzyme (i.e., precursor polypeptide containing a signal
      peptide) and that periplasmic inclusion bodies constituted an accumulation of
      proenzyme (i.e., precursor polypeptide lacking a signal peptide).

PMID- 9163952
TI  - Cloning and expression of the Bacillus sphaericus 2362 mosquitocidal genes in a
      non-toxic unicellular cyanobacterium, Synechococcus PCC6301.
AB  - Genes encoding the mosquitocidal binary toxin of Bacillus sphaericus 2362 were
      introduced into Synechococcus PCC6301, a cyanobacterium that can tolerate a
      number of potential variations in the mosquito breeding environment, and can
      serve as a food source for mosquito larvae. The toxin genes, preceded by a
      Synechococcus rbcL promoter, were located on a mobilizable Escherichia coli
      Synechococcus shuttle vector, which was introduced into Synechococcus PCC6301 at
      frequencies of 10(-5)-10(-7) exconjugants/recipient, depending on the selective
      conditions used. Recombinant Synechococcus exhibited significant toxicity against
      2-day-old and 6-day-old Culex quinquefasciatus larvae, the concentration required
      to kill 50% of larvae (LC50) being 2.1 x 10(5) and 1.3 x 10(5) cells/ml
      respectively. Mosquitocidal activity decreased tenfold after 20 generations of
      non-selective growth.

PMID- 9163953
TI  - The Propionibacterium freudenreichii hemYHBXRL gene cluster, which encodes
      enzymes and a regulator involved in the biosynthetic pathway from glutamate to
      protoheme.
AB  - A clone that can complement both Escherichia coli hemB and hemL mutations was
      found among plasmids containing the Propionibacterium freudenreichii hemB gene,
      which encodes delta-aminolevulinic acid dehydratase. The regions upstream and
      downstream of the hemB gene were sequenced. Two open-reading frames (ORF1 and 
      2), which were similar to the hemY gene encoding protoporphyrinogen oxidase and
      the hemH gene encoding ferrochelatase from Bacillus subtilis, were found upstream
      of the hemB gene. ORF1 and -2 complemented the E. coli hemG mutation, defective
      in protoporphyrinogen oxidase, and the hemH gene respectively. Since ORF1 had no
      homology to hemG, the gene was designated hemY. The hemYHB genes appeared to be
      within the same transcription unit. Downstream from the hemB gene, three open
      reading frames were found. One of these, transcribed in the same direction as the
      hemB gene, was identical to be the hemL gene, which encodes glutamate-1
      semialdehyde 2,1-aminomutase. The other two open-reading frames, located between
      the hemYHB and hemL genes, were transcribed divergently, and their deduced amino
      acid sequences showed similarities to a membrane-bound transport protein and a
      transcriptional regulatory protein respectively. The two genes may thus be
      involved in hem transport and the regulation of hem gene expression respectively,
      and were tentatively named hemX and hemR. Although hemX and hemL are unlikely to
      be part of the same operon, hemYHBXRL are clustered on the P. freudenreichii
      chromosome.

PMID- 9163954
TI  - Isolation of isoflavones from soy-based fermentations of the erythromycin
      producing bacterium Saccharopolyspora erythraea.
AB  - A search for an abundant and economical source of isoflavones, particularly
      genistein, led to the discovery that the erythromycin-producing organism
      Saccharopolyspora erythraea also produces this promising new cancer-prevention
      agent. Erythromycin fermentation is a large-scale, soybean-based process used
      world-wide for the commercial production of this medically important antibiotic.
      Results from this study indicate that genistin (the glucoside form of genistein),
      which is added to the fermentation in the soybean media, was converted to
      genistein through the action of a beta-glucosidase produced by the organism.
      Genistein was co-extracted with erythromycin from the fermentation broth, then
      separated from erythromycin during the second step of the purification process
      for the production of erythromycin.

PMID- 9163955
TI  - Isolation of freeze-tolerant laboratory strains of Saccharomyces cerevisiae from
      proline-analogue-resistant mutants.
AB  - Since some amino acids, polyols and sugars in cells are thought to be
      osmoprotectants, we expected that several amino acids might also contribute to
      enhancing freeze tolerance in yeast cells. In fact, proline and charged amino
      acids such as glutamate, arginine and lysine showed a marked cryoprotective
      activity nearly equivalent to that of glycerol or trehalose, both known as major
      cryoprotectants for Saccharomyces cerevisiae. To investigate the cryoprotective
      effect of proline on the freezing stress of yeast, we isolated proline-analogue
      resistant mutants derived from a proline-non-utilizing strain of S. cerevisiae.
      When cultured in liquid minimal medium, many mutants showed a prominent increase,
      two- to approximately tenfold, in cell viability compared to the parent after
      freezing in the medium at -20 degrees C for 1 week. Some of the freeze-tolerant
      mutants were found to accumulate a higher amount of proline, as well as of
      glutamate and arginine which are involved in proline metabolism. It was also
      observed that proline-non-utilizer and the freeze-tolerant mutants were able to
      grow against osmotic stress. These results suggest that the increased flux in the
      metabolic pathway of specific amino acids such as proline is effective for
      breeding novel freeze-tolerant yeasts.

PMID- 9163956
TI  - Growth conditions of Aspergillus sp. ATHUM-3482 for polygalacturonase production.
AB  - A wild type of Aspergillus sp. ATHUM-3482 produced extracellular
      polygalacturonase when grown in liquid medium containing citrus pectin as sole
      carbon source. A number of factors affecting enzyme activity were investigated.
      Polygalacturonase activities as high as 4.3 U ml-1 (reducing-group-releasing
      activity) and 17 U ml-1 (viscosity-diminishing activity) were obtained under
      optimum growth conditions. With sugar-beet as sole carbon source the respective
      activities were 6.5 U ml-1 and 40 U ml-1, the highest achieved in this work.
      Under these conditions no pectin lyase or pectinesterase activity was detected.
      The above yields of polygalacturonase activity compare favourably with those
      reported for fungi grown under similar growth conditions.

PMID- 9163957
TI  - Effect of xylitol and trehalose on dry resistance of yeasts.
AB  - The effects of dehydration/rehydration on two strains of Saccharomyces
      cerevisiae: S600, a metabolically engineered xylose-utilising strain, and H158,
      the non-xylose-utilising host strain; and on the naturally xylose-utilising yeast
      Pachysolen tannophilus CBS 4044, were compared after glucose and xylose
      utilisation respectively. The yeast strains differed in their ability to excrete
      and accumulate intracellular xylitol. A high intracellular xylitol content before
      and after dehydration coincided with a higher viability after a dehydration/
      rehydration cycle. The intracellular trehalose content increased during
      dehydration in all three yeast strains, but this did not correspond to enhanced
      cell viability after dehydration/rehydration. The results are discussed in
      relation to the ability of xylitol and trehalose to structure water.

PMID- 9163958
TI  - Screening for fungi intensively mineralizing 2,4,6-trinitrotoluene.
AB  - Within a screening program, 91 fungal strains belonging to 32 genera of different
      ecological and taxonomic groups (wood- and litter-decaying basidiomycetes,
      saprophytic micromycetes) were tested for their ability to metabolize and
      mineralize 2,4,6-trinitrotoluene (TNT). All these strains metabolized TNT rapidly
      by forming monoaminodinitrotoluenes (AmDNT). Micromycetes produced higher amounts
      of AmDNT than did wood- and litter-decaying basidiomycetes. A significant
      mineralization of [14C]TNT was only observed for certain wood- and litter
      decaying basidiomycetes. The most active strains, Clitocybula dusenii TMb12 and
      Stropharia rugosa-annulata DSM11372 mineralized 42% and 36% respectively of the
      initial added [14C]TNT (100 microM corresponding to 4.75 microCi/l) to 14CO2
      within 64 days. Micromycetes (deuteromycetes, ascomycetes, zygomycetes) proved to
      be unable to mineralize [14C]TNT significantly.

PMID- 9163959
TI  - [Eponyms and acronyms].

PMID- 9163960
TI  - [Pseudotumoral abdominal cysto-steato-necrosis: an unusual etiology].
AB  - We report an unusual case of subcutaneous pseudo-neoplastic focal fat necrosis in
      a woman with a Mersilen plate placed outside the abdominal wall muscles. To our
      knowledge, this association has not been previously reported in the radiologic
      literature. The differential diagnosis using ultrasound and computerized
      tomography is discussed.

PMID- 9163961
TI  - [Cystic lymphangioma of the pancreas. Apropos of a case].
AB  - A new case of pancreatic cystic lymphangioma is reported in a young woman. The
      authors discuss its clinic and histologic features and emphasize the
      complementary findings of ultrasonography and CT scan which are similar to the
      other sites of cystic lymphangioma in adults.

PMID- 9163962
TI  - [Appendiceal mucocele. Apropos of 6 cases].
AB  - Appendicular mucocele is a rare lesion presenting a combination of several
      histological lesions. It generally ruptures into the peritoneum and rarely into
      the retroperitoneum. The objective of this study was to examine the various
      radiological appearances of appendicular mucocele and to report three cases of
      mucocele which ruptured into the retroperitoneum. This retrospective series of 6
      cases of histologically confirmed appendicular mucocele was collected by the
      Central Radiology Department of Ibn Rochd University Hospital in Casablanca. The
      mean age of the patients was 61.6 years (33 years-77 years) and the sex ratio was
      4/2. A plain abdominal X-ray and ultrasonography were performed in all patients.
      Five patients were examined by CT scan and two underwent a barium enema. Five out
      of six mucoceles ruptured: into the peritoneal cavity in 2 cases with gelatinous
      ascites and into the retroperitoneum in 3 cases. The plain abdominal X-ray showed
      a mass in the right flank, which was calcified in 2 cases. Ultrasonography and CT
      scan were suggestive of the diagnosis of appendicular mucocele in only two cases.
      The case of non ruptured mucocele consisted of a clearly delimited, thin-walled
      collection. A loculated effusion with scalloping on the liver was observed in the
      two cases of gelatinous ascites. In the three cases of mucocele rupturing into
      the retroperitoneum, ultrasonography and CT scan showed a loculated
      retroperitoneal collection. This collection extended into the right psoas in 2
      out of 3 cases. Gelatinous ascites is the usual complication of appendicular
      mucocele; but in rare cases of mucocele of a retrocaecal appendix, the mucus may
      enter the retroperitoneum.

PMID- 9163963
TI  - [Malignant adrenocortical carcinoma with atypical aspect. Value of
      tomodensitometry and magnetic resonance imaging. Apropos of a case].
AB  - A case of large and non-functioning malignant adrenal tumor is reported. It was
      discovered incidentally during a check-up ordered because of sciatic pain caused
      by an osteolytic lesion of the sacrum. This huge abdominal tumor was suspected to
      be an adrenal tumor one the basis of the CT and MR findings. Histological
      analysis of percutaneous biopsies were unable to define the site and etiology of
      these two masses. Only histo-pathological examination of the surgical specimen
      allowed the diagnosis of adrenal cortical carcinoma.

PMID- 9163964
TI  - [Orbital hydatid cyst. Apropos of a case].
AB  - The authors report a new case of orbital hydatid cyst diagnosed in 3 year old
      children who had presented an insidious exophtalmia explored by CT Scan. The
      authors recall the CT Scan features of the orbital hydatid cyst and the
      contribution of the others imaging methods.

PMID- 9163965
TI  - [Hydatid cyst of soft tissues. Radiological aspects].
AB  - Hydatid disease of the soft tissues is rare, with a frequency between 2.4 and
      5.3% of all sites of hydatid disease. We report a retrospective study of 6 cases
      of hydatid cyst of soft tissues. The mean age of our patients was 36 years
      (range: 25 and 63 years) and the sex-ratio was 5 females to 1 male. The clinical
      symptoms consisted in a mass which had been present for a mean of 12 months.
      Plain X-rays showed a water density mass with no associated bone lesions.
      Ultrasonography and computed tomography defined the features of the hydatid
      cysts, which were situated in muscle in 5 cases and in the subcutaneous tissue in
      1 case. Their dimensions varied between 1.5 and 25 cm. All types of Gharbi's
      classification were observed. Secondary hydatid cysts outside of the soft tissues
      were observed in 2 patients. Medical imaging, essentially ultrasonography, was
      suggestive of the diagnosis. Computed tomography provided more precise
      information concerning the number, site and morphology of the lesions and was
      able to eliminate neoplastic disease.

PMID- 9163966
TI  - [Intramuscular myxoma. Apropos of a case].
AB  - Intramuscular myxoma is a relatively unusual benign tumor of soft tissues.
      Clinical examination is non specific and the definitive diagnosis can only be
      established on histology. The treatment consists of excision of the tumor. The
      prognosis is very good and recurrence is very rare. No cases of metastasis have
      been described.

PMID- 9163967
TI  - [Contribution of ultrasonography in thyroid diseases. Apropos of 100 cases].
AB  - Thyroid disease is a very common disease, essentially affecting women, and raises
      diagnostic and therapeutic problems. The objective of this study was to specify
      the value of ultrasonography in the diagnosis and aetiological orientation of
      these lesions, based on a retrospective study of 100 patients. The results of
      ultrasonography were compared to the histological results. The aetiologies
      detected were dominated by benign lesions, particularly adenomas (56 cases),
      dystrophic goitres (32 cases) and cancers (7 cases). Ultrasonography allowed the
      detection of clinically impalpable nodules with no isotope scan signs in 11% of
      cases. The ultrasonographic appearance of benign nodules was variable. Solitary
      nodules were detected in 63 cases. They were hyperechoic in 15 cases, isoechoic
      in 8 cases, cystic in 9 cases, and mixed in 31 cases. A peripheral clear halo was
      revealed in 25 cases and macrocalcifications were present in 17 cases. Malignant
      lesions were visualized in 7 cases and were solitary in 5 cases. Solitary lesions
      had a hypoechoic echostructure in 1 case, an isoechoic echostructure in 2 cases
      and a mixed echostructure in 2 cases. The margins were poorly demarcated in 3
      cases, and circumscribed without peripheral halo in 2 cases. Cervical
      lymphadenopathy was detected in 2 cases. Graves' disease, diagnosed in 2
      patients, showed a diffuse hypoechoic appearance of the entire thyroid gland.
      Ultrasonography is a sensitive morphological method for the diagnosis of thyroid
      lesions. A detailed and precise analysis of the ultrasound signs of the lesion
      can suggest that benign or malignant nature of the lesion, which can be completed
      by Doppler-ultrasound and especially ultrasound-guided needle biopsies.

PMID- 9163968
TI  - [Cost-effectiveness of and morbidity from digital subtraction angiography. A
      study of 5,817 cases].
AB  - This study was based on 5,817 patients examined by digital subtraction
      angiography (DSA) between 1984 and 1990. 5,209 patients received an intravenous
      injection of contrast agent and 608 received an intra-arterial injection. Digital
      subtraction angiography has become a routine procedure for the diagnosis of
      vascular disease in the various fields studied, as it provides images of
      diagnostic quality in 97% of cases: diagnostic quality of 95% after intravenous
      injection and 99% after intra-arterial injection. The morbidity is 1.65% for the
      intravenous route and 4.8% for the intra-arterial route. The morbidity of
      brachial artery catheterization is 5.5% DSA by intravenous injection is a low
      risk angiographic technique which represents a major economy in terms of the cost
      of the examination and the examination time, a reduction of hospital stay and
      waiting lists; these advantages are very important in the current context of
      public health.

PMID- 9163969
TI  - [Biliary fistula after elective conventional cholecystectomy].
AB  - The use or not of drainage after elective cholecystectomy has been recently
      studied, and we will discuss the real incidence of the subhepatic biliary
      collection and its clinical significance. In this sense, we studied 20 patients
      with a mean age of 45 years (4 male and 16 female), submitted to elective
      cholecystectomy according to selective techniques patterned by our group, where
      we realized ligature of all vessels of the gallbladder bed, and subhepatic
      drainage. These patients receibed 99 mTc-DISIDA at the moment we closed the
      abdomen, and in a period of 24 and 48 hours we studied its presence in the
      subhepatic bed and in the drainage material. All the patients had not post
      operative complications and none biliary drainage or subhepatic collection
      scanned. We concluded that using our preconized techniques, the subhepatic
      drainage is unnecessary after elective cholecystectomy.

PMID- 9163970
TI  - [Bacterial translocation in acute pancreatitis. Experimental study in rats].
AB  - Ninety Wistar rats were studied to confirm if the intestinal tract is a source of
      infection in acute pancreatitis. Bacterial translocation to the mesenteric lymph
      nodes, pancreas, peritoneal cavity, and blood was determined at 6 h, 24 h, 48 h
      and 96 hours after induction of non lethal acute pancreatitis. Bacterial growing
      was present in 60% (6 h), 90% (24 h), 70% (48 h) and 40% (96 h) (p < 0.05) of the
      mesenteric lymph nodes. Live bacteria were recovered from 67% (6 h), 90% (24 h),
      50% (48 h) and 40% (96 h) (p < 0.05) of the pancreas. Gram-positive bacteria
      translocate more frequently than Gram-negative bacteria in the early period (6
      h). Lately (24-96 h), Gram-negative bacteria were much more frequently isolated
      (p < 0.05). The most common organism isolated was Escherichia coli. No overgrowth
      of cecal Gram-negative bacteria was found. It is concluded that bacterial
      translocation in acute pancreatitis is an early phenomena, initially caused by
      Gram-positive bacteria and lately by Gram-negative bacteria, and associated with
      the severity of pancreatic lesions.

PMID- 9163971
TI  - Measurement of body composition changes during hemodialysis by bioimpedance
      analysis.
AB  - Monitoring of fluid exchanges during hemodialysis is essential for the safety and
      efficacy of the procedure. Bioimpedance analysis has been used for the
      measurement of body compartments in many settings, but experience during
      hemodialysis is relatively scare. In a prospective study of 28 cases of chronic
      renal failure treated by long-term hemodialysis on an outpatient basis, body
      composition studies were done immediately before and after the dialysis session.
      Methods included body weight, serum albumin, hematocrit, hemoglobin, sodium and
      osmolality. These variables were compared with impedance (BIA) findings, namely
      lean body mass, body fat, total water, extra and intra-cellular water, third
      space, and exchangeable sodium/potassium ratio. Patients lost weight and improved
      hematocrit, hemoglobin, osmolality and serum sodium during the therapy, and BIA
      measurements were consistent with these changes. Lean body mass and body fat
      markedly changed along the dialysis session (respectively -24.5% and + 7.5%), and
      these results were out of proportion regarding known gains and losses in that
      period. It is concluded that BIA was useful for monitoring water fluxes during
      hemodialysis, but provided unreliable information about body fat and lean body
      mass.

PMID- 9163972
TI  - [Perianal manifestations in Crohn's disease].
AB  - A total of 114 of 195 patients with Crohn's disease had perianal involvement. The
      average age at the beginning of symptomatology was 30.3 years. The interval
      between symptoms and diagnosis was 3.1 years. PAC was associated with colonic
      disease and in these patients, was multiple. PAC preceded intestinal disease in
      11 percent, was coincident in 66 percent and appeared later in 23 percent. Sixty
      one patients (53.5%) were operated on 104 times (1.7 operations per patient).
      None of these patients developed faecal incontinence. Two patients were treated
      with hyperbaric oxygenation. The association of perianal disease and extra
      intestinal manifestation occurred in 76 patients. There was no association in 38
      patients. Forty patients had extra-intestinal manifestation without perianal
      disease. Twenty two patients had panproctocolectomy because of perianal disease.
      Twenty one had a stoma, with or without intestinal resection. The stoma improved
      perianal symptoms, but all remain defunctioned. After mean follow-up of 8.8
      years, 45 patients present some kind of perianal complication. CONCLUSION: the
      surgical treatment of perianal disease well indicated and performed don't result
      in incontinence; PAC combined with colonic or rectal disease is associated with
      higher need of performing a proctocolectomy or a defunctioning stoma. Only 22.8
      percent presented resolution of perianal disease maintaining anal sphincter
      function.

PMID- 9163973
TI  - [Predictive factors of abandoning treatment in tuberculosis patients].
AB  - In spite of the efforts to control the spread of tuberculosis worldwide this
      disease remains one of the biggest problems in public health. Multiresistance has
      a dramatic effect in this scenario. Non compliance with treatment is directly
      related to disease spread and the appearance of multiresistance bacilli. Aiming
      to verify if it is possible to identify patients prone to non compliance from
      data obtained in the first visit we have studied a population enrolled in a
      prospective study. Among 257 consecutive patients evaluated between january 1991
      and january 1994, we compared 87 patients that abandoned treatment before six
      months (group A) with 97 that completed six months of treatment (group C). The
      abandon rate in this group as 33.85% which is larger than 12.9% rate reported by
      the Health Ministry. Comparing A to C, only the prevalence of alcoholism (A 33.3%
      x C 22.5%, p = 0.015) and risk behavior for HIV infection (A 27.6% x C 10.2%, p =
      0.046), as well as the frequency of non pulmonary disease (A 38.0% x C 24.5%, p =
      0.034) were significantly different between both groups. Regarding the moment of
      abandon (0, 1st or 3rd month) there was no difference in the A group. We conclude
      that patients at high risk of abandoning tuberculosis treatment can be identified
      with data obtained at the first visit, allowing to establish a different policy
      such as supervised treatment for this population.

PMID- 9163974
TI  - [Breast tuberculosis: case report and literature review].
AB  - The authors present a case of tuberculosis of the breast as the AIDS--defining
      illness in a male adult patient, with CD4 counts still moderately low (475
      cells/mm3) and without evidence of tuberculosis in any other organ. Literature
      review emphasizes the rarity of the isolated infection of the breast, especially
      in males, with no increase in the number of cases of this infection site even in
      patients with AIDS.

PMID- 9163975
TI  - [Metastasis of kidney carcinoma to thyroid gland seventeen years after resection
      of primary tumor].
AB  - Renal cell carcinoma is an unpredictable tumor that can recur many years after
      the original diagnosis. Metastasis of this tumor to the thyroid is an uncommon
      occurrence that can cause clinical and pathologic problems in diagnosis. The
      authors report case that present clinically as a palpable thyroid nodule 17 years
      after the primary renal cell carcinoma had been resected. This lesion appeared a
      solitary "cold" nodule on iodine 131 scan and was misdiagnosed as primary thyroid
      neoplasm. The diagnosis was facilitated by the use of immunohistochemical study.

PMID- 9163976
TI  - [Ocular toxoplasmosis. Utilization of immunohistochemical reaction for
      diagnosis].
AB  - The diagnosis of ocular toxoplasmosis is based primarily on clinical presentation
      and laboratory tests described else where. Eventually, unusual clinical
      presentation, as well unusual pathologic findings occur, mainly in
      immunosuppressed individuals. The authors report a case of a female patient from
      Parana with a progressive ocular disease, for at least three years, without
      definite diagnosis. After an exhaustive clinical and laboratory investigation, as
      well empiric medical treatment, without success, it was decided to enucleate the
      atrofic organ and to proceed to a histologic examination. It revealed a cronic
      and inspecific inflammatory process without any specific agent. However the
      immunohistochemical technique was able to detect Toxoplasma gondii antigens in
      the ocular tissue. This technique provides an alternative method for the
      diagnosis of unusual forms of toxoplasmosis.

PMID- 9163977
TI  - [Brain death protocol].

PMID- 9163978
TI  - [Proposal of residency integrated with medical masters degree at the UFMG Medical
      School: an evaluation among residents].
AB  - A project which integrates medical RESIDENCY with medical masters degree has been
      discussed and is expected to be set up at UFMG Medical School in the near future.
      Such project is optional for the entering residents and aims those who are
      interested in becoming researchers. This paper's objective is to raise the
      residents' opinion on the project as well as their interests in post graduation
      level. A 240 university hospital residents (HC-UFMG) and a 114 non-university
      hospital (IPSEMG) were studied through questionnaire application. From the total
      population of 354 residents we had a 50% questionnaire devolution, 120 (68%) from
      HC-UFMG and 57 (32%) from IPSEMG. Residents of different clinical and surgical
      areas were included, 55% male and 45% female. Most of them work exclusively in
      residency activities, 69% have interest in specialize after residency, 55% in
      taking medical masters degree, 52% in taking up academic life and 67% in applying
      for the integrated residency-master degree program. Twelve (7%) are not
      particularly interested in join the program because they are not sure whether
      they are able to carry on adequately both residency and research activities at
      the same time. This study shows that residents are highly receptive to the UFMG's
      program and that more detailed information concerning its contents should be
      handed out in order to generate further discussion.

PMID- 9163979
TI  - Cytomegalovirus infection in a day-care center in the municipality of Sao Paulo.
AB  - The prevalence of antibodies against cytomegalovirus (CMV) and the incidence of
      CMV infection were tested in 98 children aged 5 to 36 months who attended the day
      care center of a University hospital in Sao Paulo. At the beginning of the study
      the overall prevalence of anti-CMV IgG antibodies was 44% (43/98). Saliva and/or
      urine samples were obtained from 38 of the 43 children that were seropositive at
      the beginning of the study for isolation of the virus, and 52.6% of these
      children were found to excrete CMV in one of the two materials. Among the 37
      children that were initially seronegative from whom it was possible to obtain a
      new blood sample 6 to 12 months later, 22 (59.5%) presented seroconversion. The
      rate of viral excretion through urine or saliva from the children that
      seroconverted was 50%. These results indicate that CMV infection is frequent and
      occurs early among the children who attend this day-care center. However,
      controlled studies using molecular epidemiology techniques are needed to define
      more precisely the role of day-care centers in CMV dissemination.

PMID- 9163980
TI  - Evidences against a significant role of Mus musculus as natural host for
      Angiostrongylus costaricensis.
AB  - Wild rodents have been described as the most important hosts for Angiostrongylus
      costaricensis in Central America and southern Brazil. Sinantropic rodents
      apparently do not play a significant role as natural hosts. A search for natural
      infection failed to document worms in 14 mice captured in the house of a patient
      with diagnosis of abdominal angiostrongylosis and experimental infection of a
      "wild" Mus musculus strain and groups of albino swiss mice were carried out.
      Mortality was not significantly different and varied from 42% to 80% for Swiss
      mice and from 26% to 80% for "wild" mice. The high mortality of a "wild" M.
      musculus infected with A. costaricensis was very similar to what is observed with
      most laboratory mice strains. These data may be taken as indications that M.
      musculus is not a well adapted host for A. costaricensis, although susceptibility
      was apparently higher with "wild" populations of M. musculus as compared to Swiss
      strain.

PMID- 9163981
TI  - Cross-reactivity of antibodies in human infections by the kinetoplastid protozoa
      Trypanosoma cruzi, Leishmania chagasi and Leishmania (viannia) braziliensis.
AB  - We have detected antibodies, in the sera of Chagas disease, Kala-azar and
      Mucocutaneous leishmaniasis patients, that bind multiple antigens shared between
      the three causative agents. The Chagas disease sera showed 98 to 100% positive
      results by ELISA when the Leishmania braziliensis and Leishmania chagasi antigens
      were used, respectively. The Kala-azar sera showed 100% positive results with
      Trypanosoma cruzi or L. braziliensis antigens by immunofluorescence assays. The
      antibodies in the sera of Mucocutaneous leishmaniasis patients showed 100%
      positive results by ELISA assays with T. cruzi or L. chagasi antigens.
      Furthermore, the direct agglutination of L. chagasi promastigotes showed that 95%
      of Kala-azar and 35% of Mucocutaneous leishmaniasis sera agglutinated the
      parasite in dilutions above 1:512. In contrast, 15% of Chagas sera agglutinated
      the parasite in dilutions 1:16 and below. Western blot analysis showed that the
      Chagas sera that formed at least 24 bands with the T. cruzi also formed 13 bands
      with the L. chagasi and 17 bands with the L. braziliensis. The Kala-azar sera
      that recognized at least 29 bands with the homologous antigen also formed 14
      bands with the T. cruzi and 10 bands with the L. braziliensis antigens. Finally,
      the Mucocutaneous leishmaniasis sera that formed at least 17 bands with the
      homologous antigen also formed 10 bands with the T. cruzi and four bands with the
      L. chagasi antigens. These results indicate the presence of common antigenic
      determinants in several protozoal proteins and, therefore, explain the serologic
      cross-reactions reported here.

PMID- 9163982
TI  - Resistance of streptococcus pneumoniae to antimicrobials in Sao Paulo, Brazil:
      clinical features and serotypes.
AB  - To study resistance to antimicrobials, serotypes and clinical features of S.
      pneumoniae in S. Paulo, Brazil, 50 patients with a positive culture were
      evaluated: 7 were considered carriers and 43 had pneumococcal infections.
      Pneumonia and meningitis were the most common infections. Mortality was 34% and
      underlying diseases were present in 70%. Relative resistance to penicillin
      occurred in 24% and complete resistance was not detected. Resistance to
      tetracycline was 32% and to sulfamethoxazole/trimethoprim 32%; one strain had
      intermediate susceptibility to erythromycin; no resistance was present for
      chloramphenicol, rifampin or vancomycin. Resistance to at least one of the drugs
      tested occurred in 62%. Results by the E-test for penicillin were similar to
      those by the agar dilution method. There were 24 different serotypes and 74% of
      the strains belonged to the 23-valent vaccine including all the penicillin
      resistant strains. In this study S. pneumoniae caused severe infections and
      presented a high resistance rate to commonly used antimicrobials. Routine
      surveillance of resistance and the use of vaccination, as well as the restriction
      of inappropriate use of antimicrobials, are recommended in Sao Paulo, Brazil.

PMID- 9163983
TI  - Progression of Salmonella enteritidis phage type 4 strains in Sao Paulo State,
      Brazil.
AB  - A total of 574 S. Enteritidis strains (383 from human sources and 191 from non
      human sources) isolated between 1975-95, in Sao Paulo State, Brazil, were
      phagetyped. Among the strains isolated during the period of 1975-92, 80.9% of
      them belonged to phage type 8 (PT-8), but in 1993 strains of PT-4 accounted for
      65.2% of all the S. Enteritidis isolates. In the following years, PT-4 strains
      accounted for 99.7% and 98.4% of phagetyped S. Enteritidis strains. The results
      obtained suggested that the current epidemic of S. Enteritidis in Sao Paulo State
      is clearly associated with the progression of PT-4 strains.

PMID- 9163984
TI  - Gastrointestinal translocation as a possible source of candidemia in an AIDS
      patient.
AB  - Apart from cryptococcosis and histoplasmosis, which are mycoses contained by T
      cell-mediated mechanisms of host defense, fungemia is rarely found in AIDS
      patients. The frequency of fungemia due to Candida spp. has been reported to be
      as low as 1%. We report a non-neutropenic AIDS patient who presented a candidemia
      which probably arose from her gastrointestinal tract.

PMID- 9163985
TI  - Four adult hemoglobin types in one mulatto family.
AB  - The studied family showed the presence of four different types of hemoglobin. The
      family member who gave rise to this study (=propositus) presented Hb C and the
      hybrid Hb CG-phila. The propositus has three children, all of which have Hb AC;
      none of the family members showed any clinical symptoms. The investigation of the
      hemoglobin arose from the finding of target red cells in a blood test done during
      the pre-operatory examination for lower limb varicose vein stripping. The hybrid
      Hb CG-phila is due to two gene pairs, each of which with individual expression,
      determining the synthesis and the particular type subunits. The hybrid Hb CG
      phila is formed by the combination velocity of the subunits alpha 2G-phila beta
      2; therefore the proportion of the hybrid Hb CG-phila is lower than Hb G-phila
      and Hb C. The identification and molecular characterization of Hb G-phila showed
      the position alpha 2(68) Asn-->Lys beta 2 and Hb C showed alpha 2 beta 2(6) Glu-
      >Lys.

PMID- 9163986
TI  - Epidemiology of neurocysticercosis in Brazil.
AB  - A revision of literature was done with the objective of tracing an epidemiologic
      profile of neurocysticercosis (NCC) in Brazil. The prevalence was 0.12-9% in
      autopsies. The frequency was 0.03-7.5% in clinical series and 0.68-5.2% in
      seroepidemiological studies. The disease corresponds to 0.08-2.5% of admissions
      to general hospitals. Patient origin was rural in 30-63% of cases. The most
      involved age range (64-100%) was 11 to 60 years, with a predominance (22-67%)
      between 21 and 40 years. The male sex was the most affected (51-80%). In the
      severe forms there was a predominance of urban origin (53-62%) and of the female
      sex (53-75%). The period of hospitalization ranges from 1 to 254 days and 33 to
      50% of patients suffer 1.7 +/- 1.4 admissions. The clinical picture was variable,
      with a predominance of epileptic syndrome (22-92%) and intracranial hypertension
      (19-89%). Psychiatric manifestations were associated in 9-23% of patients.
      Lethality was 0.29% in terms of all diseases in general and 4.8-25.9% in terms of
      neurologic diseases. The asymptomatic form was detected in 6% of patients in
      clinical series and in 48.5% of case from autopsies. The racemose form and
      ventricular localization also was observed as asymptomatic form. Among the
      patients with cutaneous cysticercosis 65% of them showed neurologic
      manifestations.

PMID- 9163987
TI  - Norfloxacin monodose use in patients with cholera in Salta Argentina.
AB  - The use of monodose (800 mg) per os of Norfloxacin was evaluated in 32 patients
      with cholera at Salvador Mazza's Hospital, Salta, Argentina. It was considered
      the celerity in negativization of stool culture (100% of cases: 12 hours post
      administration), it efficiency along time (24/24 controlled patients were
      negative at 10th day) and MIC of isolated strains (100% of strains were
      sensitive: range 0.008 to 0.016 micrograms/ml). It was included oral
      administration of sorbitol 70% in peanut oil in order to study patients at 10th
      day's control. This method could be an alternative one in the study of
      asymptomatic carrier. Norfloxacin monodose shows good performance in early
      negativization of stool culture and it was also effective along the whole
      observation period, suggesting it could prevent carriage.

PMID- 9163988
TI  - Concomitant high prevalence of hepatitis C virus antibodies and hepatitis B virus
      markers in a small village of the Amazon Region, Mato Grosso State, Brazil.

PMID- 9163989
TI  - Occurrence of Biomphalaria tenagophila (D'Orbigny, 1835) in the Municipality of
      Ilhabela, at the seacoast of Sao Paulo, Brazil.

PMID- 9163990
TI  - TRH-TSH test in patients with schistosomiasis chronic forms.

PMID- 9163991
TI  - Paracoccidioides loboi (Fonseca Filho et Area Leao, 1940) Almeida et Lacaz, 1948
      1949. Description of the fungus in Latin.

PMID- 9163993
TI  - A simple and inexpensive method to generate a microaerophilic atmosphere for the
      isolation of Campylobacter sp.
AB  - Faeces of 138 chickens were inoculated on Blaser agar plates. One set of plates
      was incubated in jars with CampyPak envelopes. The others were incubated in "Zip
      lock" plastic bags (7 x 8 in.) and a microaerophilic atmosphere was generated
      exhaling into the "Zip-lock" plastic bag, after holding the breath for 20 sec.
      Then, the bag was pressed to evacuate its atmosphere, inflated again, and pressed
      (4 times), and finally sealed. Campylobacter was isolated from 127 (96.2%) of
      samples incubated in jars with gas generator envelopes and from 129 (98%) of the
      specimens incubated into the bags. The proposed methodology offers good savings
      for cost-conscious laboratories.

PMID- 9163992
TI  - Seropositivity for anti-trypanosoma cruzi antibodies among blood donors of the
      "Hospital Universitario Regional do Norte do Parana", Londrina, Brazil.
AB  - The most frequent form of acquisition of Chagas' disease in endemic areas was the
      transmission through the feces of contaminated triatominae. However, special
      attention should be paid in urban areas to transmission by blood transfusion,
      justifying the compulsory screening of blood donors. Early investigations at
      blood banks in the town of Londrina, Brazil, demonstrated that the seroprevalence
      of anti-Trypanosoma cruzi antibodies among blood donors was approximately 7.0% in
      the fifties. Further studies demonstrated practically the same seroprevalence
      until the eighties. In an attempt to obtain data about the real dimension of the
      seropositivity for anti-Trypanosoma cruzi antibodies in the region, the authors
      carried out a large-scale study on 45,774 serum samples from blood donors of the
      Hemocentro of Hospital Univesitario Regional do Norte do Parana (HURNP),
      Universidade Estadual de Londrina. The immunological tests were done at the
      Division of Clinical Immunology of HURNP from May 1990 to December 1994. The
      serum samples were studied by the indirect hemagglutination assay (IHA, using
      kits commercially obtained from EBRAM) and by indirect immunofluorescence (IFI,
      using kits from LIO SERUM) with anti-human IgG conjugate (LABORCLIN). The results
      demonstrated that 643 serum samples were positive in both assay corresponding to
      a seroprevalence of 1.4%, i.e., a significant decrease in anti-Trypanosoma cruzi
      antibodies in the region in comparison with the previously mentioned rates. Data
      correlating sex and age of seropositive blood donors are presented, as well as
      the possible factors that may have contributed to the results observed.

PMID- 9163994
TI  - Hepatitis G virus/GB virus C in Brazil. Preliminary report.
AB  - Hepatitis G virus/GB virus C is a novel flavivirus recently detected in hepatitis
      non A-E cases. In this study, the presence of this virus in chronic non-B, non-C
      hepatitis patients was evaluated using GBV-C specific PCR and this virus was
      detected in one out of thirteen patients. This patient has presented a severe
      liver failure, has lived for a long time in the Western Amazon basin and no other
      cause for this clinical picture was reported. The impact of the discovery of this
      new agent is still under evaluation throughout the world. The study of the
      prevalence of this virus among chronic hepatitis patients and healthy individuals
      (as blood donors) will furnish subside to evaluate its real pathogenicity.

PMID- 9163995
TI  - [One year after WOSCOP, what is the correct pharmacological treatment of primary
      hypercholesterolemia? Reflexions du Groupe de Pharmacologie Clinique de la
      Societe Francaise de Cardiologie].

PMID- 9163996
TI  - [Dietary fats and athero-thrombosis: approach to the knowledge of a balanced
      lipid diet].

PMID- 9163997
TI  - [Hypolipidemic agents. Groupe de Travail et Groupe de Lecture de la Conference de
      Consensus Hypolipidemiants].

PMID- 9163998
TI  - [Treatment of aplastic anemia with cyclosporine, prednisolone and androgens
      (primary results apropos of 10 cases].
AB  - Aplastic anaemia is a potentially fatal haematopoietic disorder whose aetiology
      is not yet clarified. In our preliminary study we have introduced cyclosporin in
      the aplastic anaemia treatment to evaluate its effect on the disease evolution.
      Ten aplastic anaemia patients, mean age 33.33 +/- 20.01 years, were treated with
      cyclosporine (9 +/- 2.35 mg/kg/d), prednisolone (0.5 mg/kg/d) and androgens (1
      mg/kg/d). The prednisolone was always combined with cyclosporine. The androgens
      were administered concomitantly with the cyclosporine or alternately. Seven
      patients responded to the treatment after a median remission delay of 6 weeks (2
      12 weeks). They became independent of blood requirements at a median of 36 weeks
      (8-108 weeks); the three other patients died during the first trimester without
      showing any improvement. Among the seven responders, two relapsed early and
      transiently. The rate of actuarial survival was 70 per cent. The median duration
      of survival was 10.5 months. The side effects observed included one case of
      malignant lymphoma, six cases of liver toxicity and five cases of kidney
      toxicity. This toxicity was reversible after dose adjustment of the cyclosporine.
      In our study, the introduction of cyclosporin in the aplastic anaemia treatment
      resulted in improved therapeutic response. Androgens should be used to maintain
      the haematologic response. This therapeutic protocol associated with drug
      monitoring seems promising and the side effects should not limit its use because
      of the severity of the underlying disease.

PMID- 9163999
TI  - [Arterial hypertension: current large therapeutic trials].
AB  - In this review, the design and objectives of ongoing clinical trials in essential
      hypertension are discussed along with the main results obtained from previously
      published therapeutic trials. In a meta-analysis of 14 of the major primary
      prevention trials in hypertension, the difference in diastolic blood pressure
      between the intervention groups and the control groups was only 5-6 mmHg. This
      difference was associated with significant reductions in all stroke events (42
      per cent), all coronary heart disease events (14 per cent) and in cardiovascular
      mortality (21 per cent). In elderly hypertensive patients, available studies have
      shown that antihypertensive treatment reduces the incidence of non-fatal
      cardiovascular events without significantly modifying cardiovascular mortality.
      Most of these results were obtained with beta-blockers or diuretics. Despite
      official recommendation as first line monotherapy, none of the three new
      antihypertensive classes has been shown to have beneficial effects on hard
      primary endpoints such as cardiovascular morbidity and mortality. Several ongoing
      large scale randomized controlled trials vs. beta-blockers or diuretics are
      addressing this important issue. Moreover, other effects of antihypertensive
      treatment such as the 'J-curve phenomenon', the rate of change in the carotid
      wall thickness or the exact beneficial effects in elderly patients are being
      investigated in some of these studies.

PMID- 9164000
TI  - [Non-steroidal anti-inflammatory agents and cyclooxygenases].

PMID- 9164001
TI  - [Orphan drugs: problem of public health and economic stakes].
AB  - Orphan drugs (OD) qualify as drugs scientifically viable but not viable from an
      economic point of view either because the number of patients who might benefit is
      too small or because the populations concerned are too poor to afford the drugs.
      Sick people who could be treated by OD and their families have been fighting for
      years to induce authorities in charge of health to set up a programme to
      stimulate research into new treatment for rare diseases. The United States,
      initiated work in order to confer status on OD leading to the Orphan Drug Act in
      1983. It defined the conditions for attribution of the OD status and also made
      attractive proposals to pharmaceutic industries in order to improve their
      development. More recently, in 1993, Japan took similar decisions, while the
      European Union and France are also on the way, as recent meetings of European
      ministers of health show. In contrast, developing countries are still excluded
      from medical research as very few tropical diseases have treatment. Legislation
      for OD, first planned to make up for the high costs of research and development,
      proved its efficiency. But ODs must move to a new status as some are now becoming
      the object of important economic stakes.

PMID- 9164002
TI  - [Methodology of preparing a list of educational objectives: example of
      application to pharmacology. Groupe Objectifs Pedagogiques de L'Association des
      Enseignants de Pharmacologie].
AB  - Using a structured approach to categorize pharmacological knowledge and a
      systemic analysis of prescribing practice, we identified the knowledge needed to
      optimally prescribe and manage treatments with drugs. The approach consisted in
      finding the branched chains of knowledge beginning with each operation required
      to solve each problem which arises in prescribing and managing drugs at the most
      elementary level. This elementary knowledge is then transformed into educational
      objectives. The next step is to share the educational objectives between basic
      medical training, continuing medical education and acquisition of therapeutic
      knowledge. The method could be applied in other medical teaching domains.

PMID- 9164003
TI  - [Example of a phase IV trial involving several physicians and aiming at answering
      a scientific question: EOL].
AB  - The aim of this trial was to test the hypothesis that a reduced number of doses
      improves compliance in current medical practice. Compliance with twice a day
      dosage was compared with compliance with three doses a day. Two bioequivalent
      presentations of nicardipine were used, the regular presentation (t.i.d.) and the
      slow-release (b.i.d.). The trial was controlled, randomized, open, in two
      parallel groups: (1)'t.i.d.' group: one tablet of regular nicardipine, 20 mg,
      three times a day, three months; (2) 'b.i.d.' group: one capsule of slow-release
      nicardipine, twice a day, three months. 2651 general practitioners randomized
      7274 hypertensive patients. The primary criterion was documented in 93.7 per cent
      of the cases at the end of the trial. The remaining 6.3 per cent comprised
      treatment withdrawal (2.8 per cent) and patients lost to follow-up (3.5 per
      cent). The primary criterion study was compliance, assessed by a self
      questionnaire filled in by the patient and a standardised interview by the
      physician. Compliance was slightly better in the b.i.d. group than in the t.i.d.
      group (p < 0.001). Remaining pill count was also used but it was a failure. A
      random sample of investigators made on-site visits. Discordant data were
      infrequent and were limited to dates of visits. Difficulties with on-site visits
      were mostly due to a rather frequent lack of source records.

PMID- 9164004
TI  - [Thrombocytopenic purpura after isolated or combined vaccination against measles,
      mumps and rubella].
AB  - A retrospective epidemiological survey was conducted to evaluate the incidence
      and characteristics of thrombocytopenic purpura (TP) reported in France following
      measles, mumps or rubella vaccination with monovalent or multivalent vaccines.
      Sixty cases of TP were reported i.e an incidence/100,000 doses of 0.23 and 0.17
      for measles or rubella vaccines respectively given alone, to 0.87 for combined
      measles-rubella vaccine and 0.95 for MMR vaccine. The mean age was 21 +/- 12
      months and the delay of diagnosis was 16 +/- 6 days after vaccination.
      Thrombopenia was severe (mean platelet count: 8000 +/- 6000/mm3) and always
      associated with purpura. The immediate outcome was favourable in 89.5 per cent of
      cases. Vaccine-associated TP appears to be similar to acute childhood idiopathic
      thrombocytopenic purpura but the clear temporal relationship between MMR
      vaccination and the occurrence of TP make a causal relationship highly plausible.
      Acute TP seems a rare complication of measles-rubella and MMR vaccination but
      clinicians had to be informed of the possibility of their occurrence. Acute TP
      following vaccination should be reported by physicians to their Regional Drug
      Surveillance Centre.

PMID- 9164005
TI  - [Aseptic meningitis after mumps vaccination].
AB  - The aim of this retrospective study was to evaluate the incidence and the
      characteristics of spontaneously reported aseptic meningitis (AM) in France
      following mumps vaccination with monovalent or multivalent vaccines containing
      the Urabe strain. Fifty-four cases of AM were reported to the regional drug
      surveillance centres or to the manufacturer from the time each vaccine was
      launched up until June 1992. Twenty cases were associated with the time off
      administration of a monovalent mumps vaccine and 34 with a trivalent measles,
      mumps and rubella vaccine (MMR). A mumps virus was isolated in four cases in the
      cerebrospinal fluid and an Urabe-like strain was characterised twice by
      polymerase chain reaction (PCR). A probable mumps origin was assumed in 17 other
      cases where the patients presented with other clinical or biological signs of
      mumps infection. The clinical outcome of AM was always favourable. The global
      incidence of mumps vaccine-associated AM was 0.82/100,000 doses, which is
      significantly lower than the incidence in the unvaccinated population. Even
      considering that the actual incidence of AM is much higher when assessed by
      active surveillance studies, the risk/benefit ratio of mumps vaccine remains in
      favour of vaccination. The incidence of mumps vaccines containing Jeryl Lynn (ROR
      Vax et Imu ORR) associated with AM needs to be evaluated.

PMID- 9164006
TI  - [Prevention of congenital toxoplasmosis with spiramycin; value and limits of
      levels in amniotic fluid].

PMID- 9164007
TI  - [Pseudo-Creutzfeldt-Jakob syndrome with long-term lithium use].

PMID- 9164008
TI  - Drinking habit as a base for blood pressure elevation--difference in
      epidemiological significance by beverage type.
AB  - To investigate whether blood pressure differs by taking preferred alcoholic
      beverage among habitual drinkers, systolic and diastolic blood pressure (SBP,
      DBP) were compared among groups with different beverage types in 563 middle-aged
      Japanese males using data from a cross-sectional health survey conducted from
      February, 1989 through March, 1991 in five areas of Japan. Mean values of SBP and
      DBP, adjusted for residence, age and body mass index (BMI), were significantly
      greater in 'exclusively sake' drinkers (adjusted SBP: 127.2 mmHg, adjusted DBP:
      83.0 mmHg) and in 'exclusively shochu' drinkers (adjusted SBP: 127.5 mmHg,
      adjusted DBP: 84.2 mmHg) than in non-drinkers (adjusted SBP: 120.9 mmHg, adjusted
      DBP: 77.3 mmHg). Adjusted SBP and DBP of 'exclusively beer' drinkers (adjusted
      SBP: 121.9 mmHg, adjusted DBP: 79.1 mmHg) were significantly (for SBP: p = 0.016,
      for DBP: p = 0.008) lower than those of 'exclusively sake' drinkers. Similar
      patterns of blood pressure differences between five beverage types of habitual
      drinkers were found especially in the group with less than 150 g of weekly ethyl
      alcohol consumption. Even after adding ethyl-alcohol consumption as a covariate
      among 479 habitual drinkers, the significant differences in adjusted SBP and DBP
      between 'exclusively beer' drinkers and 'exclusively sake' drinkers (for SBP: p =
      0.032, for DBP: p = 0.044) were noted. These results may suggest that the effects
      of drinking on blood pressure differ by beverage type in middle-aged Japanese
      males.

PMID- 9164009
TI  - Effects of changes in arousal level by continuous light stimulus on contingent
      negative variation (CNV).
AB  - The purpose of the present study was to investigate an inverted-U relationship
      between contingent negative variation (CNV) and arousal level which was
      influenced by extraneous environment. As an extraneous stimulant, stimulation by
      light was adopted, and five levels of luminance conditions, 10 cd/m2, 100 cd/m2,
      320 cd/ m2, 1,000 cd/m2, and 1,800 cd/m2 were provided randomly. Under five
      luminance conditions, seven subjects who had been accustomed a measurement of CNV
      executed simple reaction time tasks to evoke CNV. Outside CNV, spontaneous EEG
      prior to S1 was measured as an indicator for arousal level. As a result, a
      negative correlation existed between the logarithm of luminance and the relative
      power value of alpha waves at Fz. Otherwise, an increase in luminance caused an
      increase in CNV amplitude until the luminance level reached 320 cd/m2, beyond
      which however CNV amplitude was found to decrease. These tendencies were most
      remarkable in the phase of early CNV at Fz. The low amplitude of early CNV seen
      in the high luminance conditions was inferred to have been induced by excessive
      arousal state because of the low relative power value of alpha waves, while the
      low amplitude in the low luminance conditions was inferred to have been induced
      by low arousal state because of the high relative power value of alpha waves.
      However, changes in arousal level by light stimulus caused no effect on reaction
      time. From these findings, it was suggested that a definite "inverted-U"
      relationship existed between the change in arousal level by light stimulation and
      resultant CNV, and that it could be discriminated as to whether reduction in CNV
      is caused by excessive arousal effect of environment by analyzing spontaneous EEG
      preceding S1.

PMID- 9164010
TI  - A dynamic model of the human/clothing/environment-system.
AB  - In this paper a dynamic model of the human/ clothing/environment-system is
      developed. The human body (controlled system) is subdivided into six segments
      consisting of the head, trunk, arms, hands, legs and feet. Each segment is
      further divided into the core, muscle, fat, and skin layer. The afferent signal
      of the controlling system is composed of the weighted temperatures measured by
      thermal receptors at sites distributed in the body. The difference between this
      signal and its threshold activates the thermoregulatory actions: vasomotor
      changes, metabolic heat production and sweat production. The model considers the
      competition between skin and muscle blood flow during exercise in hot
      environments because of limited cardiac capacity, as well as cold induced
      vasodilatation. Additionally a combined model of heat and mass transfer from the
      skin through clothing to the environment is developed and incorporated into the
      thermoregulatory model. The human/clothing model can be used to investigate the
      interaction between the human body, clothing and environment. The model is
      validated by comparing the simulation with experimental results under different
      conditions: heat, cold, exercise, clothing and transient phases. It turns out
      that the simulation is compatible with the experimental results. We conclude that
      the model can be applied in a broad range of environmental conditions.
      Application of the model is easy via a user-friendly interface i.e. a WINDOWS
      shell.

PMID- 9164011
TI  - Relation between smoking and periodontal disease by oral hygiene status in
      Japanese factory workers.
AB  - The relation between smoking and periodontal disease as classified by the
      Community Periodontal Index of Treatment Needs (CPITN) code was investigated in
      1,611 Japanese male factory workers in Osaka, 20-59 years of age. The Simplified
      Debris Index (DI-S) according to the Simplified Oral Hygiene Index was employed
      as an index for the quantity of dental plaque. For the items related to smoking,
      a self-reporting form on smoking, the number of years of smoking, and the number
      of cigarettes smoked was distributed prior to the oral examination. Our results
      indicated the following: in the group with a poor state of oral hygiene, the
      negative effects of smoking were evident, resulting in unhealthy periodontal
      tissue. We believe that this result further confirms the contention that the
      removal of dental plaque is most important as a prophylaxis for periodontal
      diseases, and public education about this negative consequence of smoking will
      further strengthen prophylactic measures.

PMID- 9164012
TI  - Aerobic bacteria isolated from blood cultures of patients and their antibiotic
      susceptibilities in Harare, Zimbabwe.
AB  - OBJECTIVE: To assess the extent of involvement of different types of gram
      positive and gram negative bacteria and incidence of monomicrobial and
      polymicrobial cases in patients with bacteremia but without a record of the
      underlying clinical conditions of the patients. Antibiotic susceptibility
      patterns of isolates were also determined to guide clinicians in the management
      of such bacteremic cases especially where routine sensitivity testing is not
      performed. DESIGN: Case series. SETTING: The study comprised patients attending
      different clinics in Parirenyatwa Hospital, Harare. SUBJECTS: A total of 817
      blood cultures from patients, comprising 469 and 348 males and females
      respectively. There were no records of the underlying clinical conditions of the
      patients. MAIN OUTCOME MEASURES: Prevalence rates of organisms and their
      antibiograms using standard techniques and Kirby-Bauer disc diffusion method.
      RESULTS: Results obtained revealed that only 303(37.1%) of the 817 total samples
      screened were positive for either monomicrobial or polymicrobial bacteremia. Two
      hundred and eighteen (71.9%) and 85 of positive cultures were Gram positive and
      Gram negative bacteria respectively. Coagulase negative staphylococci (CNS)
      strains were the predominant organisms isolated (42.9%). Other organisms isolated
      were Staphylococcus aureus (11.6%), Escherichia coli (6.9%), Salmonella spp.
      (8.3%), Klebsiella spp. (5.3%), whereas Pseudomonas aeruginosa, Haemophilus
      influenzae, Enterobacter and Micrococcus species each accounted for less than 4%.
      Antibiogram patterns showed multiple resistance of S. aureus and CNS to
      Penicillin, Erythromycin and Methicillin. All isolates of S. pyogenes (10), S.
      pneumoniae (18) and Micrococcus spp (10). were susceptible to penicillin.
      Ciprofloxacin, Clindamycin, Fusidic acid and Gentamycin were highly active
      against gram positive organisms except that Gentamycin was inactive against S.
      pneumoniae. Ceforoxime, Erythromycin and Ceftriazone also showed good activities
      against Gram positive organisms. All (10) isolates of P. aeruginosa were
      susceptible to Polymyxin B, Carbenicillin and Ciprofloxacin. Ciprofloxacin,
      Norfloxacin and Gentamycin were highly active against all Gram negative bacteria.
      CONCLUSION: For infections due to both Gram positive and Gram negative bacteria,
      Ciprofloxacin and Gentamycin would be appropriate for therapy whereas Fusidic
      acid and Clindamycin may, in addition, be recommended for Gram positive
      organisms. It is also concluded that a prevalence rate of 37.1% of bacteremic
      cases existed in the sampled population and that monomicrobial cases were more
      predominant.

PMID- 9164013
TI  - Pleural tuberculosis in patients infected with HIV in Addis Ababa.
AB  - OBJECTIVE: To determine the prevalence of HIV-1 infection in patients with
      pleural tuberculosis and compare the clinical and radiological characteristics,
      effects and side effects of drugs, compliance to treatment and outcome by HIV
      status. DESIGN: A hospital based, prospective study. SUBJECTS: 90 adult patients
      with pleural tuberculosis. 120 surgical patients admitted for non-HIV related
      conditions served as controls. SETTING: Black Lion Hospital, a tertiary care
      referral hospital in Addis Ababa, Ethiopia. RESULTS: 22% of the patients with
      pleural tuberculosis versus 6.7% for the controls (p < 0.01) were seropositive
      for HIV-1. Amongst patients with pleural tuberculosis, HIV seropositive patients
      were more likely to be male, and had longer duration of illness prior to coming
      to hospital (p < 0.05). They had more disseminated disease (p < 0.01), bilateral
      pleural effusion (p < 0.05), adverse reaction to anti-tuberculosis drugs (p <
      0.05) and increased mortality (p < 0.05). Hepatitis was the most common side
      effect observed. There was no difference in size of the effusion, clinical
      improvement, radiographic resolution or defaulter rate. CONCLUSION: HIV
      associated pleural tuberculosis commonly occurs with other forms of extra
      pulmonary tuberculosis and responds well to treatment. Hepatitis is a frequent
      side effect and entails poor prognosis. We therefore recommend careful
      documentation of a previous history of liver disease and baseline investigation
      of liver function tests before initiation of treatment. The finding of bilateral
      pleural effusion may indicate the presence of underlying HIV infection.

PMID- 9164014
TI  - Fractures in children in south eastern Nigeria.
AB  - OBJECTIVES: To evaluate the pattern of fractures in children in the south eastern
      region of Nigeria, seeking to highlight the planning and designs of buildings,
      roads and playgrounds to prevent paediatric fractures. DESIGN: Retrospective
      review of paediatric patients with fractures who presented at the only tertiary
      referral centre in the region. SETTING: A university teaching hospital situated
      in the south eastern corner of Nigeria. SUBJECTS: 102 paediatric patients treated
      for fractures between January 1993 and December 1995. MAIN OUTCOME MEASURES:
      Causes of fractures and their anatomical distribution. RESULTS: 71 boys and 31
      girls were treated for fractures. The commonest cause of fractures was road
      traffic accidents accounting for 50% of the patients, followed by falls and
      collapsing mud walls. Most of the fractures seen (58 patients) were of the green
      stick type. The femur was the commonly fractured bone (25 patients) followed by
      the radius (22 patients) and humerus (20 patients). Road traffic accident victims
      presented earlier at the hospital than victims of other causes. Also lower limb
      fracture patients presented earlier than patients with upper limb fractures.
      CONCLUSION: Paediatric fractures are amenable to conventional conservative
      therapy and open reduction became necessary in long neglected cases with
      associated malunion. Since the causes of fractures are largely preventable,
      public enlightenment campaigns, provision of pedestrian pathways, care on the
      part of school authorities and proper structural construction of the traditional
      houses may help reduce the number of cases of fracture in our environment.

PMID- 9164015
TI  - Use of mental health institutions in Zimbabwe and factors affecting length of
      stay of patients.
AB  - OBJECTIVE: To explore the functioning of mental health care institutions and the
      factors contributing to prolonged length of stay of in-patients. DESIGN: The
      study was a descriptive type which employed convenient and stratified simple
      random sampling procedure to select the institutions and the study subjects.
      Patients were categorized according to diagnostic grouping and sample sizes were
      calculated in proportion to ward size and sex. Data was collected through face to
      face interviewing, administration of the questionnaire, completion of a
      checklist, observation of hospital records and patient activities as well as
      studying of patient case notes. SETTING: The study was done at Ngomahuru and
      Ingutsheni in Masvingo and Bulawayo respectively. SUBJECTS: The subjects of the
      study comprised patients and selected health cadres. MAIN OUTCOME MEASURES:
      Length of stay of inpatients by diagnostic grouping and factors contributing to
      prolonged stay of in-patients. RESULTS: The two institutions were functioning as
      both homes and hospitals with more patients needing more social than medical
      care. Factors affecting length of stay included destitution, lack of community
      based rehabilitation therapy facilities, poor follow up after discharge and
      institutionalization of patients. CONCLUSIONS: Mental health care institutions
      are experiencing prolonged stay of patients of years or a life time. This has
      implications on costs and quality of services provided in feeding, clothing and
      caring for them medically. There is need to consider alternative cost effective,
      and efficient options of care.

PMID- 9164016
TI  - Does an antimalarial drug history mean anything?
AB  - OBJECTIVE: To determine the validity of an antimalarial drug history. DESIGN:
      During a chloroquine sensitivity study carried out from 27 February to 13 April,
      1995, an antimalarial drug history was obtained from the patients. A urine test
      was used as a gold standard to screen for antimalarial drugs in these patients.
      SETTING: Two Mutare district primary health care centres. SUBJECTS: Fifty
      clinical malaria cases were screened. MAIN OUTCOME MEASURES: Cases were
      classified in a two by two contingency table based on the reported antimalarial
      drug and the results of the urine test. Positive predictive value and negative
      predictive value were then examined.

PMID- 9164017
TI  - Agent and nature of childhood injury and initial care provided at the community
      level in Ibadan, Nigeria.
AB  - Daily home interviews-examinations were carried out for a period of three months
      to obtain information on the agent (object) involved, nature (diagnosis) and care
      provided to children aged zero to 19 years, following accidental injury, in
      Idikan community, Ibadan. During the study period, 1286 injuries were recorded
      involving all the 436 children in the study community. Rocky outcrops, chairs,
      broken bottles, tables, knives and glasses were the major agents of injuries
      (91.0%). Puncture wounds, lacerations, haematomas, sprains and dislocations
      constituted most of the nature of injury (96.5%). All injuries were minor
      injuries (AIS = 1). Relatives-neighbours were responsible for managing majority
      of the injuries. Only seven (0.6%) injuries were seen by a nurse-physician in a
      health facility. Specific individual-community health education as well as health
      service and environmental modification measures are suggested. This study has
      also shown that community based data on injury provides more precise information
      required for the development of injury prevention and care programmes at the
      primary care level.

PMID- 9164018
TI  - Non-ketotic hyperglycaemia presenting as Epilepsia partialis continua.

PMID- 9164020
TI  - Histologically diagnosed benign neoplasms in black children and adolescents.

PMID- 9164019
TI  - Gender dynamics and the challenges for HIV prevention.
AB  - Information on the transmission of the human immunodeficiency virus (HIV),
      leading to acquired immunodeficiency syndrome (AIDS), has been widely
      disseminated since the early 1980s, and yet curbing new infections remains a
      major public health dilemma. In response to the global challenge of HIV/AIDS,
      most control and prevention interventions have targeted "core groups' with
      messages which include:- 1. Reduction of individual risk through responsible
      sexual behaviour or behaviour change, such as, delayed sexual debut, abstinence,
      monogamy and condom use. 2. Communal (as a society) adoption of a risk reduction
      strategy e.g. reduced rate of sexual partner change and avoiding multiple
      partners. 3. Improved, early and aggressive STD treatment programmes. However,
      data from sub-Saharan Africa and elsewhere shows how the epidemic, in the general
      population, appears to thrive unabatted. Large proportions of women and some men,
      in none of the traditional high risk core groups, are increasingly becoming
      infected with HIV. Most of the women appear to be at risk of infection not so
      much because of their own behaviour, but that of their partners of husbands. In
      this continuum, our response has been fragmented and non-strategic. Few programme
      activities have been developed that address men as a critical core group
      potentially propagating or sustaining the epidemic. The preoccupation with female
      sex workers and other core groups (e.g. truck drivers) could have overshadowed
      the need for programmes and interventions that make men, in general, aware of HIV
      risk and less likely to infect their sexual partners. Challenges posed by HIV
      require innovative strategies that foster behavioural and social change in the
      situation of men at risk and their partners.

PMID- 9164021
TI  - Health transition: the economic issues.

PMID- 9164022
TI  - Bovine spongiform encephalopathy and Sri Lanka.

PMID- 9164023
TI  - Lessons from four studies on the management of snake bite in Sri Lanka.

PMID- 9164024
TI  - Adolescent pregnancies--is the outcome different?
AB  - OBJECTIVE: To compare the obstetric complications and mode of delivery between
      adolescent pregnancies and pregnancies of women over 20 years. DESIGN: A
      prospective study of all pregnant mothers delivered at General Hospital,
      Anuradhapura during a period of two years from January 1993. SUBJECTS: 1600
      pregnant adolescents and 14699 pregnant women over 20 years. RESULTS: The
      percentage of adolescent pregnancies during this period was 9.8%. The incidence
      of pregnancy induced hypertension among adolescent women was 2.3% and 2.2% in
      women over 20 years. The still birth rate was 2.4% in adolescent pregnancies and
      2.2% in women over 20 years. The incidence of breech presentation was 2.2% in
      both groups. There was a statistically significant difference (P < 0.001) in the
      incidence of low birth weight among live births between adolescents (33.6%) and
      women over 20 years (22.7%). Adolescent women had a caesarean section rate of 7%
      and a forceps delivery rate of 2.3% compared to 11.4% and 2.0% in mothers over 20
      years, a statistically significant difference. CONCLUSIONS: Adolescent women were
      not at an increased risk for pregnancy induced hypertension, still birth or
      breech presentation. The incidence of low birth weight and normal vaginal
      delivery were significantly higher among adolescent women.

PMID- 9164025
TI  - Intensive care utilisation following attempted suicide through self-poisoning.
AB  - OBJECTIVE: To evaluate intensive care utilisation following attempted suicide
      through self-poisoning. DESIGN: Retrospective analysis of clinical records.
      SETTING: Intensive Care Unit, Teaching Hospital, Peradeniya. PATIENTS: All
      patients admitted over the period 1991-1995. RESULTS: 292 patients were admitted
      after a suicide attempt by ingestion of a poisonous substance or drug in
      overdose. 52% were mechanically ventilated. The mean stay was 6 days. Daily
      intensive care cost averaged Rs. 8000 for a ventilated patient. Fifty three
      patients died. The 292 patients constituted 10.2% of the total admissions to the
      unit. CONCLUSIONS: Suicide as a medical emergency imposes pressure on the limited
      resources and facilities available in intensive care units. Concrete preventive
      measures are mandatory to prevent loss of life and health care resources.

PMID- 9164026
TI  - Fetal gender determination using ultrasound scanning.

PMID- 9164027
TI  - Practical aspects of aerosol therapy in asthma (2): Metered dose inhalers and
      spacers.

PMID- 9164028
TI  - First reports of subcutaneous sparganosis in Sri Lanka.
AB  - OBJECTIVE: To report and create awareness of sparganosis, a parasitic zoonosis
      caused by a larval stage of Spirometra sp. SETTING: Two patients with non-tender
      subcutaneous lumps. DIAGNOSIS CRITERIA: Morphology of solid cestode larva in
      excision biopsies. CONCLUSIONS: Although these two instances were innocuous,
      infection is potentially dangerous as larvae are long lived and could invade
      vital organs. The most likely source of infection in Sri Lanka is ingestion of
      the infected first intermediate host, Cyclops, in water.

PMID- 9164029
TI  - Familial amyloid polyneuropathy in a Sri Lankan family.
AB  - A woman who presented with features of peripheral sensory, motor and autonomic
      neuropathy and amyloid deposits in the vitreous due to familial amyloid
      polyneuropathy (FAP) is described. Her father had died of a similar illness and
      one of her brothers and her two children had lesions suggestive of early amyloid
      deposits in the vitreous. Reports of familial amyloidosis are rare from Asian
      countries and it has not been reported in Sri Lanka previously.

PMID- 9164030
TI  - Acute colonic pseudo-obstruction associated with varicella zoster infection and
      acyclovir therapy.

PMID- 9164031
TI  - Finding parts of a gravid female Wuchereria bancrofti in a breast aspirate.

PMID- 9164032
TI  - Massive hepatomegaly in multiple myeloma.

PMID- 9164033
TI  - Spontaneous rupture of a liver cell adenoma.

PMID- 9164034
TI  - Sexual abuse of illegally adopted children.

PMID- 9164035
TI  - A case of congenital intrahepatic biliary dilation (Caroli's disease)

PMID- 9164036
TI  - Rheumatic heart disease in Gondar College of Medial Sciences Teaching Hospital:
      socio-demographic and clinical profile.
AB  - One hundred fourteen patients with rheumatic heart disease were seen between
      January 1994 and January 1995 at Gondar College of Medical Sciences Teaching
      Hospital. These patients were prospectively described using a prepared study
      protocol consisting of socio-demographic variables, clinical findings and
      laboratory tests. The mean and median age of the patients were 23 +/- 8 years and
      22 years, respectively, (range = 5-50 years). About 66% of the patients were
      females with female to male ratio of 1.9:1. Eighty five cases (74.6%) were on
      follow up with mean and median duration of 4.32 +/- 4.5 years and 3 years,
      respectively (range = 1-20 years). The rest (25.4%) of the patients were new.
      History findings suggestive of rheumatic fever were obtained in 26% of the
      patients. Six patients (5.3%) had siblings with similar illness. Frequently
      encountered valve lesions were combined mitral regurgitation and stenosis seen in
      29 (25.4%), followed by pure mitral stenosis in 25 (21.9%) and mitral
      regurgitation in 21 (18.4%). The commonest arrhythmia was atrial fibrillation,
      observed in 22.8% of the cases. Recurrence of rheumatic fever occurred in 11
      patients (9.6%) over the study period. Of these, five were regularly taking a
      four weekly Banzanthine penicillin injections. The functional classes of patients
      according to the New York Heart Association's classification were 17%, 25%, 26%
      and 32% for classes I, II, III and IV, respectively. There were 85 episodes of
      decompensations. The commonest precipitating factor was drug discontinuation
      followed by infection and arrhythmia. Most episodes have multiple causes for
      deterioration. Critical evaluation and education of patients during follow up is
      recommended.

PMID- 9164037
TI  - Ocular manifestations of leukaemia in Ethiopians.
AB  - A prospective ophthalmic evaluation of 74 newly diagnosed and 34 old (on follow
      up) leukaemic patients, carried out from March 1990 to December 1995 is
      described. Primary ocular involvement, that is leukaemic retinal infiltrates,
      were detected in 32% of the newly diagnosed. In contrast, none of the old
      leukaemic patients had this lesion. In 69% of the new and 21% of the old cases,
      secondary ocular manifestations of leukaemia were observed. The major secondary
      ocular manifestation of leukaemia in both groups was intra-retinal haemorrhage. A
      variety of miscellaneous ocular findings, such as cataract, pterygium,
      pingeculae, etc. were detected in 36% of all leukemics. These findings indicate
      the importance of a complete ophthalmologic evaluation in the diagnosis, follow
      up and management of leukaemic patients.

PMID- 9164038
TI  - Management of children with ARI and/or diarrhoea in Addis Ababa, Ethiopia.
AB  - This study, conducted between May 9 and May 19, 1994 in twenty health centres in
      Addis Ababa, looks at the quality of care provided for children presenting to
      public sector health centres in Addis Ababa with ARI and/or diarrhoea. As has
      been documented in other countries, both developing and developed, inappropriate
      prescription of medications is common in Addis Ababa. Forty four per cent of
      children received useless or potentially harmful drugs; in 97 of 99 cases of
      "sore throat", antibiotics were prescribed; only 14 of 116 children with the
      diagnosis of "common cold" received no medication. While 88 percent of children
      with diarrhoea received ORS, and 39 per cent of children with pneumonia were
      given appropriate medications, few caretakers knew how to use them properly.
      Caretakers' knowledge of appropriate home care of children with ARI and diarrhoea
      (feeding, use of fluids and indication for return to the clinic) was found to be
      deficient. Causes for poor quality of care are discussed, and recommendations for
      solving some of the problems identified, and for further research, are presented.

PMID- 9164039
TI  - Sexual behaviour, and knowledge and attitude towards HIV/AIDS among out of school
      youth in Bahir Dar Town, northwest Ethiopia.
AB  - Intervention to control the spread of HIV/AIDS in out of school youth is under
      way in Bahir Dar Town. This survey was therefore conducted in April 1994 to
      provide baseline data on sexual behaviour, knowledge and attitude towards
      HIV/AIDS. A total of 1115 out of school young people from eight randomly selected
      kebeles of the town were interviewed. Fifty one (4.6%) respondents said they have
      never heard of AIDS. Mean number of sexual partners for those who practised sex
      was 3.9 +/- 2.5. Knowledge scores were better than attitude and practice scores.
      Age, sex, marital status, educational status and occupation were significantly
      related with knowledge, attitude and practice scores (p < 0.05). The association
      of knowledge scores with attitude and practice scores was not statistically
      significant; p = 0.056 and p = 0.07, respectively. In addition to improving
      knowledge, emphasis should be given to other measures such as making the services
      accessible to the youth. A similar survey is recommended after the intervention
      programme is over.

PMID- 9164040
TI  - Screening of aflatoxins in Shiro and ground red pepper in Addis Ababa.
AB  - Aflatoxin contamination of Shiro and ground red pepper samples collected from
      government owned good stores, retail shops and open markets in. Addis Ababa was
      investigated. From sixty samples each of ground red pepper and Shiro, 8 (13.33%)
      and 5 (8.33%) were positive for aflatoxins, respectively. Only aflatoxin B1 was
      detected in both types of foodstuff. There was no significant difference between
      the proportion of aflatoxin contained in both ground red pepper and Shiro
      samples. Aflatoxin levels in Shiro and ground red pepper positive samples ranged
      from 100 to 500 ppb and 250 to 525 ppb, respectively. The mean levels of
      contamination by aflatoxin in ground red pepper was significantly higher (p <
      0.05) than that of Shiro. Though statistically not significant, the number of
      positive samples were more in samples from open markets when compared to samples
      from government owned food stores and retail shops. Conclusions are drawn that
      ground red pepper and shiro traded in Addis Ababa can be considered as high risk
      commodities for which routine survey of aflatoxins may be necessary.

PMID- 9164041
TI  - Hypertrophic pulmonary osteoarthropathy in pulmonary metastasis--a case report.
AB  - Hypertrophic pulmonary Osteoarthropathy is most commonly encountered in
      association with bronchogenic carcinoma and tumours of the pleura. Its
      association with pulmonary metastasis from extrathoracic neoplasms is rare. We
      report a 33 years old male Ethiopian who presented with Cannon ball lesions,
      clubbing of the digits, periostitis, gynaecomastia, acromegalic features and
      bilateral knee arthritis. Related literature is briefly reviewed.

PMID- 9164042
TI  - Population history of north Africa: evidence from classical genetic markers.
AB  - After an intensive bibliographic search, we compiled all the available data on
      allele frequencies for classical genetic polymorphisms referring to North African
      populations and synthesized the data in an attempt to reconstruct the
      populations' demographic history using two complementary methods: (1) principal
      components analysis and (2) genetic distances represented by neighbor-joining
      trees. In both analyses the main feature of the genetic landscape in northern
      Africa is an east-west pattern of variation pointing to the differentiation
      between the Berber and Arab population groups of the northwest and the
      populations of Libya and Egypt. Moreover, Libya and Egypt show the smallest
      genetic distances with the European populations, including the Iberian Peninsula.
      The most plausible interpretation of these results is that, although demic
      diffusion during the Neolithic could explain the genetic similarity between
      northeast Africa and Europe by a parallel process of gene flow from the Near
      East, a Mesolithic (or older) differentiation of the populations in the
      northwestern regions with later limited gene flow is needed to understand the
      genetic picture. The most isolated groups (Mauritanians, Tuaregs, and south
      Algerian Berbers) were the most differentiated and, although no clear structure
      can be discerned among the different Arab- and Berber-speaking groups, Arab
      speakers as a whole are closer to Egyptians and Libyans. By contrast, the genetic
      contribution of sub-Saharan Africa appears to be small.

PMID- 9164043
TI  - Genetics of the Chuetas (Majorcan Jews): a comparative study.
AB  - A study of the Chueta population has been carried out to establish the genetic
      relationships between the Chuetas and other Jewish and non-Jewish circum
      Mediterranean populations and to identify which markers discriminate better
      between these populations. The analyses used were principal components analysis,
      factorial analysis of correspondences, and stepwise discriminant analysis. The
      results indicate that most of the Jewish communities resemble each other and
      other Middle Eastern populations, because of their common origin, but they also
      have affinities with their host peoples. The results also agree with those of
      most researchers in the importance of G6PD, FY, and MN as geographic markers and
      in the role of HP, GLO1, and Rh as indicators the Middle Eastern origin of the
      Jews but differ with respect to the geographic pattern of ABO. Moreover, the
      Jewish origin of the Chuetas remains evident in their genetic pool, although they
      resemble their neighboring populations more than other Jewish populations.
      Finally, HP, G6PD, ABO and Rh are the most important variables in determining the
      position of the Chuetas with respect to other Jewish and non-Jewish populations.

PMID- 9164044
TI  - New method for comparing levels of microdifferentiation: application to migration
      matrices of two populations from the Basque Country (Spain).
AB  - Population microdifferentiation rates can be obtained by various coefficients.
      Despite differences in the formulations of these coefficients, the obtained
      values lead to convergent empirical interpretations. One of the most widely used
      coefficients is Wright's FST. Insofar as all these statistics depend on the
      number of subpopulations r and their effective size Ne, they are far from easy to
      compare and interpret. Here, we propose a new method for comparing
      microdifferentiation rates: a measurement referred to as -log(p), inferred from
      the relationship between the statistics FST and chi 2. The most interesting
      quality of -log(p) is that it is independent of r and Ne so that its use
      facilitates comparisons between populations with different characteristics. Using
      parent-offspring migration matrices, we estimated the values of -log(p) for two
      populations in the Basque Country: Lanciego and Orozco. The obtained values were
      compared with the -log(p) for other world populations whose microdifferentiation
      rates had already been calculated by other researchers using different data
      sources. Both Basque populations showed low -log(p) values, as did most of the
      considered continental populations, whereas island and nonmodern populations
      showed higher values. This implies microdifferentiation only in island and
      nonmodern populations, although the secular trend of this process in some
      populations, such as the Aland Islanders and the Papago, leads to isolation
      breakdowns.

PMID- 9164046
TI  - Serological analysis of the Abbad Tribe of Jordan.
AB  - The Abbad are one of the largest tribes in Jordan with a complex structure
      dictated by historical and cultural factors. To study the genetic variability
      within the tribe, we examined four samples representing different levels of
      tribal structure for the polymorphisms of five blood groups, five erythrocyte
      enzymes, and seven serum proteins. The obtained allele distributions indicate a
      wide range of genetic variability within the tribe. An allelic heterogeneity test
      revealed significant differences between the examined samples, yet a gene
      diversity analysis revealed no significant substructuring. The observed genetic
      relationships among the four samples appear to agree with the tribal
      organization. Endogamous mating within the tribe and inbreeding within the
      subunits are believed to be the main factors that influenced the observed
      variability. This was confirmed by the results of the R matrix analysis, which
      summarized the genetic relationships in concordance with intertribal admixture,
      when affiliation and historical and maternal links were considered. The study is
      also an example of gene diffusion and of a negative relationship between the FY A
      B- phenotype and endemicity of malaria.

PMID- 9164045
TI  - Spontaneous abortion pattern in an isolated Mediterranean population: La Alta
      Alpujarra Oriental (southeast Spain).
AB  - The effects of several family and embryonic factors on the abortion pattern in a
      rural Mediterranean population (La Alta Alpujarra Oriental, Southeast Spain) were
      analyzed from interview data on 3163 pregnancies from the first half of the
      twentieth century. No significant differences in spontaneous abortion rates were
      detected between endogamous and exogamous couples. The abortion pattern of this
      population is characterized mainly by family and embryonic factors. High rates of
      early abortions were significantly associated with maternal age and pregnancy
      order, and parental consanguinity was linked with a notable decrease of abortion
      frequency during the earlier stages of pregnancy. A tendency toward a higher risk
      for abortion was also confirmed for twinship of the fetus. The interactions
      identified between abortion risk and maternal age, pregnancy order, and
      inbreeding emphasize the important contribution of sociodemographic factors to
      prereproductive mortality in human populations.

PMID- 9164047
TI  - Apolipoprotein B and E genetic polymorphisms in the Cayapa Indians of Ecuador.
AB  - Three DNA polymorphisms (XbaI, EcoRI, and Ins/Del) of the apolipoprotein B (APOB)
      gene and the CfoI polymorphism of the APOE gene were investigated in a sample of
      96 Cayapa Indians from Ecuador. The frequencies of the X+ (0.182), R+ (1.000),
      and Del alleles (0.432) at the three APOB sites were found to be higher than and
      to differ significantly from those reported for East Asians. No comparisons could
      be made between the Cayapa and other native Americans because of the lack of data
      on these sites. We observed in our sample that, like native American populations
      but unlike East Asians, the APOE allele frequencies were characterized by the
      absence of the APOE*2 allele and by a high frequency of the APOE*4 allele
      (0.280). Besides a probable drift effect, the high APOE*4 value was tentatively
      attributed to an effect of selection. Because this allele enhances the absorption
      of cholesterol by the intestine, it could confer an advantage to carriers in an
      unfavorable environment (i.e., diet poor in cholesterol).

PMID- 9164048
TI  - Prevalence, geographic distribution, and genealogical investigation of Machado
      Joseph disease in the Azores (Portugal).
AB  - Machado-Joseph disease (MJD) is an autosomal, dominantly inherited
      neurodegenerative disorder of adult onset. The prevalence of MJD reaches its
      highest values in the islands of the Azores. A research program was undertaken to
      study the origin and spread of the mutant gene in the Azorean populations. Here,
      we present the first results of such a study. The Azorean MJD patients are
      grouped in 34 families and are distributed on 4 of the 9 Azore islands. Values of
      prevalence, carrier rate, and number of individuals at risk are reported. The
      genealogies of the patients were reconstructed to identify the founders. An
      analysis of the geographic distribution of the birthplaces of the patients
      compared with the birthplaces of the founders revealed the existence of areas
      that are clusters for both, thus defining crucial sites for the origin of the
      disease. Preliminary results on the number of links between the affected families
      show that 64.7% of them have at least one link with another MJD family. So far, a
      single source for the introduction of the mutant gene in the Azores has not been
      identified.

PMID- 9164049
TI  - Body mass index and family histories in type II diabetic propositi and
      preliminary observations on the transmission of diabetes in polygamous families.
AB  - We studied family histories of diabetes mellitus in the first-degree relatives of
      356 type II diabetic propositi in whose families monogamy is practiced. Positive
      family histories were noted in 32% of the propositi: parental 20%, sibling 14%,
      and offspring 0.6%. In 11 pedigrees with conjugal diabetic parents, 33% (18/55)
      of their offspring were diabetic. Paternal influence was significantly higher
      than maternal influence (43 of 62 vs. 19 of 62, Z = 2.86, p < 0.01). The presence
      or absence of sibling history did not depend on the body mass index in the
      propositi. We also studied pedigrees of 10 propositi in whose paternal families
      polygamy is practiced. In these families also a trend toward greater paternal
      influence was noted. We conclude that (1) a family history of diabetes is present
      in one-third of diabetic propositi, (2) paternal influence is stronger than
      maternal influence in the transmission of diabetes, (3) sibling history for
      diabetes has no relation to the body mass index of the propositi, (4) prevalence
      of diabetes is higher in the offspring of conjugal diabetic parents, and (5)
      studies in polygamous families are a new approach that may help to quantify the
      genetic load transmitted from a parent when there is heterogeneity in the
      spouses.

PMID- 9164050
TI  - Recent fertility and mortality trends among aboriginal and nonaboriginal
      populations of central Siberia.
AB  - We examine mortality and fertility patterns of aboriginal (primarily Evenki and
      Keto) and Russian (i.e., nonaboriginal) populations from the Baykit District of
      Central Siberia for the period 1982-1994. Mortality rates in the aboriginal
      population of Baykit are substantially greater than those observed in the
      Russians and are comparable to levels recently reported for other indigenous
      Siberian groups. Infant mortality rates average 48 per 1000 live births among
      Baykit aboriginals, three times greater than the Russians of the district (15 per
      1000 births) and more than double the rates for Inuit and Indian populations of
      Canada. Similarly, crude death rates of the Baykit aboriginals are twice as high
      as those observed in either the Baykit Russians or the Canadian aboriginal
      populations (13 vs 6-7 deaths per 1000 individuals). Birth rates of the
      indigenous population of Baykit are higher than those of the Russians (33 vs. 15
      births per 1000 individuals) but are comparable to those of Canadian aboriginal
      groups. Violence and accidents are the leading causes of adult male mortality in
      both ethnic groups, whereas circulatory diseases have emerged as the prime cause
      of death in women. The greater male mortality resulting from violence and
      accidents is a widely observed cross-cultural phenomenon. The emergence of
      circulatory diseases as a major mortality risk for women, however, appears to be
      linked to specific lifestyle changes associated with Soviet reorganization of
      indigenous Siberian societies. Marked declines in mortality and increases in
      fertility were observed in the Baykit aboriginal population during the mid to
      late 1980s with the government's implementation of anti-alcohol policies. The
      decline in mortality, however, was largely erased during the early 1990s, as the
      region became increasingly isolated and marginalized following the collapse of
      the Soviet Union. Demographic trends in the Baykit District suggest that because
      the indigenous groups have become more isolated, many are returning to a more
      traditional subsistence lifestyle.

PMID- 9164051
TI  - G542X as a probable Phoenician cystic fibrosis mutation.
AB  - When analyzed by origin, the frequency of the G542X cystic fibrosis (CF) mutation
      (the second most common CF mutation in Europe after DF508) varies between
      population groups in Europe. We show here that the frequency of G542X varies
      among different towns or regions of origin, being lower in northeastern Europeans
      than in southwestern Europeans. The G542X mutation mapping that we have defined
      by a multiple regression of G542X frequencies covers 28 countries (53 geographic
      points) and is based on data from 50 laboratories. The more elevated values of
      G542X frequency correspond to ancient sites of occupation by occidental
      Phoenicians.

PMID- 9164052
TI  - Analysis of mtDNA.

PMID- 9164053
TI  - The importance of healthy communities of higher education.
AB  - A framework for understanding issues that contribute to vibrant and healthy
      communities of higher education is presented. The focus is on how individual and
      community health relate to institutional missions, purposes, and goals. This
      framework may be applied to 2-year and 4-year colleges and universities whether
      they are public, private, research, teaching, sectarian, religious, residential,
      or computer institutions. The following questions are addressed: Why should
      colleges maintain healthy communities? How do we define health in colleges and
      universities? Why is this important for society? What are the key
      responsibilities in fostering healthy educational communities? Who is responsible
      for assuring that this happens? What added value do personal and community health
      yield for institutions of higher education? Readers are provided with a rationale
      for assessing the role and importance of individual and community health in their
      campus environments; engaging students, faculty, and staff in discussions about
      these issues; and determining whether more thorough, systematic, and intensive
      community health assessments or interventions are needed in their campus
      settings.

PMID- 9164054
TI  - Health problems of college students.
AB  - College health professionals deal with a range of medical problems and risky
      behaviors. Some medical conditions occur more frequently in the college-age
      population, but college health is not unique because of the types of medical
      problems seen. Community providers welcome the opportunity to deliver primary
      care to this relatively healthy population, with less emphasis on screening,
      intervention, mental health, social well-being, and altering unhealthy behaviors.
      Young people have been recognized as experiencing higher rates of morbidity,
      disability, and mortality from various developmental, environmental, and
      behavioral risk factors than the general population. These risk factors are so
      interrelated that successful efforts to change them require a more comprehensive
      approach that extends beyond the health of individuals to the wellness of an
      entire campus community. On the continuum of health and well-being, college
      health must move away from focusing on disease and move toward community
      wellness.

PMID- 9164055
TI  - Health trends among college freshmen.
AB  - Trends in college student health based on an annual survey of college freshmen
      administered for 30 consecutive years (1966-1995) at colleges and universities
      nationwide are described. Trends in the following areas are covered: (1) alcohol
      and drugs, (2) physical health, (3) psychological health, and (4) sexual
      attitudes. Gender and institutional differences in health behaviors and attitudes
      among the 1995 class of college freshmen are also considered. Major trends
      include declines in beer drinking and in physical and emotional self-confidence
      and an increase in stress and cigarette smoking. "Unhealthy" behaviors and
      attitudes are reported most often by freshmen at public 2-year institutions.

PMID- 9164056
TI  - Health risk behaviors among California college students.
AB  - Health risk behaviors among students attending 4-year colleges in California were
      examined. The Youth Risk Behavior Survey for College Students was administered in
      a two-stage (29 universities, 5,652 students) random sample. All campuses and
      3,810 (69%) students participated in the survey. In the 30 days preceding the
      survey, 36.7% of the students had binged at least once while drinking; 25.3% had
      driven after consuming alcohol; 32% had ridden in a car with someone who had been
      drinking; 17.6% had used marijuana; and 6% had carried a knife, gun, or club.
      More than half of the students who were sexually active and not married or living
      with a primary partner had not used a condom the last time they had sexual
      intercourse. Only 5% of regular bicycle riders always wore a helmet. Fewer than
      half (44%) reported aerobic physical activity on 3 or more of the preceding 7
      days. The results of this study indicate a substantial amount of serious, risky
      health behaviors among California college students.

PMID- 9164057
TI  - Binge drinking among college students: a comparison of California with other
      states.
AB  - California college students (1,864 students from 15 colleges) were compared with
      students who participated in the Harvard School of Public Health College Alcohol
      Study, which surveyed 17,592 students in 140 colleges nationwide. California
      college students, in comparison with the remainder of the nation, were less
      frequent drinkers; less frequent binge drinkers; exhibited fewer personal
      problems and risks associated with heavy episodic drinking, including drinking
      and driving; and reported fewer "secondhand" effects of binge drinking, such as
      being physically assaulted or experiencing an unwanted sexual advance. Many of
      these differences appear to be related to the California college students' being
      older, more likely to be married, and less likely to live on campus than those in
      the Harvard study. The findings suggest that, in developing programs tailored to
      local needs, there is significant value in augmenting national surveillance of
      college student health risk behaviors with the development of regional, state,
      and local surveillance systems.

PMID- 9164058
TI  - At the crossroads: options for financing college health services in the 21st
      century.
AB  - At a time when increasing numbers of uninsured and underinsured students are
      attending college, many college health programs face formidable challenges in
      their efforts to sustain services. As financial pressures increase, college
      health programs must revisit their funding options, including (1) maintaining the
      current level and source of funding but requiring additional out-of-pocket fees
      for certain services from students, (2) establishing their own insurance plans,
      (3) qualifying as a preferred provider organization, or (4) some combination of
      the above. Whatever strategies are selected and pursued, college health programs
      must continue to try to provide quality services at a reasonable cost while
      maintaining an emphasis on prevention, health education, and the provision of
      services most needed by the college population, including mental health and
      substance abuse services.

PMID- 9164059
TI  - Principles for assuring the health of college students: a California perspective.
AB  - Given the rapidity of change in both higher education and health care, re
      examining the values and precepts that undergird the profession of college health
      is an ongoing need. Reported in this article are the results of a structured
      process in which a group of college health professionals from California, along
      with others interested in the health of college students, examined several trends
      affecting higher education and health; considered possible scenarios for these
      sectors; created a shared vision for the future of college health; and developed
      strategies useful in attaining that vision. The results of these deliberations
      are presented as a set of principles that, if followed, should increase the
      likelihood that college health centers will be responsive to user needs. Although
      the article is based on a California-based conference, the principles discussed
      are almost certainly valuable for all in college health.

PMID- 9164060
TI  - Secretion of different types of gelatinases from cultured human keratinocytes.
AB  - We investigated gelatinolytic enzymes derived from cultured human keratinocytes.
      Using a zymograph, we detected 92 kDa and 72 kDa gelatinases as major components
      and 83 kDa as a minor component from a conditioned cultured medium (BSL-K110,
      Kyokutoseiyaku Co.) of keratinocytes. After several passages, the 72 kDa band
      disappeared, and the 83 kDa band became dominant in another conditioned culture
      medium (K-GM, Kurashikibouseki Co.); these keratinocytes had a relatively
      differentiated appearance. These results suggest that some mechanism may regulate
      the secretion of selected types of gelatinase from keratinocytes under different
      conditions.

PMID- 9164061
TI  - Evaluation of an avidin-biotin-peroxidase method with a monoclonal antibody to
      type IV collagen in the differential diagnosis of bullous pemphigoid and
      epidermolysis bullosa acquisita.
AB  - There are reports in which an immunohistochemical technique with a monoclonal
      antibody to type IV collagen has been employed for differentiating between
      bullous pemphigoid (BP) and epidermolysis bullosa acquisita (EBA). The aim of
      this study was to determine whether this method could be used routinely. Biopsies
      (paraffin-embedded lesional skin containing a blister) from currently diagnosed
      patients with clinical features suggesting BP or EBA were examined by an avidin
      biotin-peroxidase (ABC) technique. Sera were tested by indirect
      immunofluorescence on salt-split skin (IF) and immunoblotting (IB). In all cases
      which exhibited clear type IV collagen staining, the results of the ABC technique
      agreed with results of both IF and IB. In one confirmed EBA case, it was
      impossible to unequivocally localize type IV collagen, because it stained very
      faintly. Taking into consideration the results of our study, data indicating that
      the level of blistering might not coincide with the localization of
      immunoreactants in EBA cases and the possibility of an enzymatic destruction of
      lamina densa, we conclude that the ABC method is unsuitable for differentiation
      between BP and EBA.

PMID- 9164063
TI  - Natural history of psoriasis: a study from the Indian subcontinent.
AB  - Clinical and epidemiological data from 1220 patients with psoriasis is presented.
      Psoriatics accounted for 2.3% of the total dermatology outpatients. There was a
      distinct male preponderance. Mean age of onset was lower in women at 27.6 years,
      although the severity of the disease was the same in both sexes. Family history
      was positive in just 2% of patients. Plaque type disease was the most common,
      seen in over 93% of the patients. Lesional pruritus was a problem in 65%.
      Remission in summer was experienced by 43%. The scalp was the first site of onset
      in 25.2%. Nail and joint involvement were seen in 55.7% and 4.4%, respectively.
      Complete remission of disease activity was experienced by 35% of the patients
      during some part of the year in the course of their disease.

PMID- 9164062
TI  - Hormonal profiles and prevalence of polycystic ovary syndrome in women with acne.
AB  - One of the important etiologic factors in acne is an increase in sebaceous gland
      activity, which is androgen dependent. Acne is a common manifestation of
      hyperandrogenemia. Therefore, acne may not only cause cosmetic concern but may
      also be a sign of underlying disease. In females, the most common cause of
      hyperandrogenemia is polycystic ovary syndrome (PCOS). The purpose of this study
      was to determine the hormonal profiles of women with acne and the prevalence of
      PCOS in women attending the dermatological clinic with acne problems. The
      diagnostic criteria of PCOS were clinical findings of menstrual disturbances and
      hyperandrogenism (acne, seborrhea, hirsutism), pelvic ultrasound imaging of PCO
      (multiple subcapsular ovarian cysts 2-8 mm. in diameter, with dense echogenic
      stroma), and an elevated luteinizing hormone (LH) to follicle stimulating hormone
      (FSH) ratio. There were 51 women with acne; 20 regularly menstruating volunteers
      without acne served as a control group. PCOS was found in 19 out of 51 patients
      with acne (37.3%) and none of the control group. Twenty acne patients had
      abnormal menstruation (39.2%). Acne cases had higher mean levels of serum total
      testosterone (T), free T, dehydroepiandrosterone sulfate (DHEAS) and prolactin
      (PRL). No statistically significant difference was observed for LH, FSH or sex
      hormone binding globulin (SHBG). Because of this high prevalence of PCOS in women
      with acne, all women presenting with acne should be asked about their menstrual
      pattern and examined for other signs of hyperandrogenemia. Hormonal profile
      determination as well as pelvic ultrasonography for ovarian visualization should
      be performed to confirm the diagnosis of PCOS in female acne patients who have
      menstrual disturbances.

PMID- 9164064
TI  - Panniculitis with eosinophilic infiltration due to gabexate mesilate (FOY):
      possibility of allergic reaction.
AB  - A 59-year-old Japanese man developed septal panniculitis with eosinophilic
      infiltration in both forearms and the dorsum of the left hand after a gabexate
      mesilate intravenous drip infusion for acute pancreatitis through catheters
      implanted in these sites. Gabexate mesilate at a dose of 1000 mg per day had been
      given continuously for 8 days, and antibiotics were added by the same infusion
      route twice a day. All the infusion routes, however, became occluded one after
      the other. Reddish swelling first occurred at the left wrist 6 hours after
      occlusion of the infusion route, and, on both forearms, reddish swelling occurred
      about one week after the occlusion of each route. Patch testing revealed a +2
      reaction to gabexate mesilate (10% pet) at days 3 and 7, and skin testing
      revealed indurated erythema to gabexate mesilate (0.1% aq) at days 2 and 3. The
      specimens biopsied from the positive skin testing reaction sites showed
      perivascular infiltrate and slight septal panniculitis. The inflammatory
      infiltrate consisted predominantly of lymphocytes with small numbers of
      eosinophils. Staining of the specimen biopsied from the right forearm lesion with
      anti-eosinophil cationic protein (ECP) antibodies (EG1 and EG2) showed deposition
      of eosinophil-derived granule proteins at the damaged septal connective tissues
      of the panniculitis. The panniculitis improved with topical steroid treatment.
      This case suggested that the concentration of infused gabexate mesilate may have
      been high enough to damage blood vessels and that gabexate mesilate may have
      leaked into the surrounding connective tissues, inducing allergic reactions and
      resulting in lesions.

PMID- 9164065
TI  - Fixed drug eruption caused by iopamidol, a contrast medium.
AB  - We report a patient who developed a fixed drug eruption caused by the contrast
      medium, Iopamidol. We diagnosed it by her episode pattern and the results of
      patch tests. This substance has not been previously implicated as a cause of
      fixed drug eruption. Immunohistochemical studies showed Fas expression in
      keratinocytes of the lesion, but not in the uninvolved skin. This finding may
      explain the preferential localization of fixed drug eruption.

PMID- 9164066
TI  - Traumatic aneurysm of the temporal artery: a report of five cases.
AB  - Five cases of traumatic aneurysm of the superficial temporal artery are reported.
      Four patients clearly stated that they had sustained traumatic injuries within 3
      months prior to the appearance of the pulsating aneurysms; in the remaining case,
      more than two years had passed before the appearance of the nodule, and it was
      without pulsation. Color Doppler echography was very useful for observing the
      circulation in these aneurysms. Histologically, these cases were pseudoaneurysms
      composed of small vessels with internal elastic lamina and adjacent connective
      tissue proliferation, suggesting a break in the arterial wall.

PMID- 9164067
TI  - A unique case of squamous cell carcinoma showing adenocarcinomatous features with
      focal apocrine differentiation.
AB  - We report an 85-year-old man with squamous cell carcinoma on the right pinna. Two
      years after the excision of the lesion, metastatic foci were found extending from
      the right retromandibular to the mastoid region and into the parapharyngeal
      space. Histopathologically, the primary tumor showed interconnecting nests of
      atypical cells invading into the dermis from multiple epidermal and infundibular
      foci. The tumor had both squamous and glandular differentiation. A peculiar
      finding was the presence of decapitation secretion in the glandular foci. To our
      knowledge, definite apocrine differentiation in squamous cell carcinoma has not
      previously been reported.

PMID- 9164068
TI  - Foot ulcer due to arteriovenous malformation: report of a case.
AB  - A 41-year-old woman had erosive eruptions surrounded by irregularly shaped
      pigmentation on the lateral aspect of her right foot, where she had noted
      gradually increasing warmth and pain for 10 years. The eruptions waxed and waned
      without complete healing, and an ulcer which had formed one year previously did
      not respond to topical treatments. Arteriography performed on the right lower
      extremity disclosed multiple diffuse arteriovenous malformations in the right
      lower leg and foot. The ulcer was treated by bed rest, surgical debridement, and
      topical application of bucladesine sodium ointment. After three months, the ulcer
      healed, leaving a shallow scar and pigmentation.

PMID- 9164069
TI  - A case of apple-shaped pedunculated lipofibroma.
AB  - In 1975, Mehregan et al (1) proposed the term pedunculated lipofibroma for the
      solitary form of NLCS in the view of its distinctive clinicopathologic features.
      Subsequently, Nogita et al reported and reviewed 32 cases of pedunculated
      lipofibroma in 1994. Pedunculated lipofibroma is a relatively rare form of benign
      connective tissue proliferation abnormality characterized by ectopic adipose
      tissue in the dermis. We observed a case of pedunculated lipofibroma with a
      prominent stalk containing feeding vessels, a history of congenital onset, a
      remarkable globular apple-shaped mass and an accompanying small sessile lesion.
      We report this case with a review of the literature.

PMID- 9164070
TI  - Nuchal fibroma.
AB  - Nuchal fibroma was diagnosed in a 54-year-old diabetic woman with a two year
      history of increased skin thickness of her low-posterior neck and interscapular
      region, causing discomfort and limitation of neck and arm motion. Physical and
      laboratory examinations excluded further disorders. The patient was released,
      free from symptoms, after complete excision of the soft tissue tumor.

PMID- 9164071
TI  - A case of dermatopathia pigmentosa reticularis.
AB  - Dermatopathia pigmentosa reticularis (DPR) is a very rare disorder with the
      diagnostic triad of generalized reticulate hyperpigmentation, noncicatricial
      alopecia, and onychodystrophy. Many other dermatologic findings have been
      associated with this triad, including adermatoglyphia, hypohidrosis or
      hyperhidrosis, palmoplantar hyperkeratosis, and nonscarring blisters on the dorsa
      of the hands and feet. The mode of inheritance is unclear but may be autosomally
      dominant. To our knowledge, only 11 cases have been reported in the world, and
      none has previously been described in the Orient. We present a Korean patient
      with the typical features of the DPR triad, along with adermatoglyphia,
      hypohidrosis, and nonscarring blisters on the dorsa of the feet.

PMID- 9164072
TI  - Ulcerative lichen planus: a rare variant of lichen planus.
AB  - A 54-year-old Japanese man with ulcerative lichen planus is reported. He had a
      painful erythema with ulcers on his soles and nail dystrophy. Mucous involvement
      was present on his lip. His hairs were intact. Histopathological findings
      confirmed the diagnosis of lichen planus.

PMID- 9164073
TI  - Bilateral rheumatoid nodule development on the distal region of the soles; poor
      blood circulation and local pressure as possible causes.

PMID- 9164074
TI  - Coexistence of psoriasis vulgaris, ulcerative colitis, and thyroid adenoma.

PMID- 9164075
TI  - Enzymatic repair mechanisms for base modifications induced by oxygen radicals.

PMID- 9164076
TI  - Effect of UVA on RNA synthesis in isolated chicken liver nuclei.
AB  - Little information is available on the effects of UVA (320-400 nm radiation) on
      transcription. We examined the effect of UVA on RNA synthesis in isolated chicken
      liver nuclei. Nuclei in air or nitrogen were irradiated with UVA, and the RNA
      synthesis induced by endogenous RNA polymerase was estimated under conditions in
      which little or no initiation occurs. Incorporation of [3H]UMP into the acid
      insoluble fraction was used as the measure of RNA synthesis in the nuclei. In air
      the amount of synthesized RNA decreased with increasing UVA fluence. In contrast,
      in nitrogen UVA had little effect on RNA synthesis. Sodium azide and histidine,
      which effectively scavenge singlet oxygen (1O2) as well as hydroxyl radicals
      (.OH), protected the nuclei from inhibition of RNA synthesis; whereas, sodium
      formate and dimethyl sulfoxide, both of which much more effectively scavenge .OH
      than 1O2, had no protective effect. These findings provide a strong indication
      that 1O2 is involved in the inhibition of RNA synthesis. In addition, RNA
      polymerase II-dependent synthesis (in the nucleoplasm) was much more sensitive to
      UVA than RNA polymerase I-dependent synthesis (in the nucleolus).

PMID- 9164078
TI  - Spectrum of spontaneous mutations in the cyclic AMP receptor protein gene on
      chromosomal DNA of Escherichia coli.
AB  - We determined 46 spontaneous mutations occurring in the cyclic AMP receptor
      protein gene (crp) on the chromosomal DNA of Escherichia coli by the use of PCR
      cloning. Of 24 base substitutions, 17 were transversions and 7 transitions
      including all types of base substitutions. The frequency of the changes of A:T
      base pairs was similar to that of G:C pairs, suggesting that A:T pair is also a
      target for base substitution. Frameshifts including seven-1 and four +1
      frameshifts occurred at the sites of a run of identical bases. Deletions
      extending 18 and 172 bases occurred at the sites where the deleted sequences were
      flanked by short repeated sequences at the junction. The insertions of IS2
      element or its inverted sequence were detected in two and six mutations,
      respectively. The assay system of the mutation used here is available for the
      determination of the mutational spectrum of base substitutions.

PMID- 9164077
TI  - Reactions between hydroxyl-radical-induced 7,8-dihydro-8-oxo-2'-deoxyguanosine
      precursor and the spin trap alpha-phenyl-N-tert-butylnitrone.
AB  - An N2O-saturated aqueous solution containing 2'-dG and the spin trap agent PBN
      was examined by ESR and HPLC-ECD methods after X irradiation. ESR examination
      showed that the ESR spectrum obtained consisted of signals due to the PBN-OH and
      PBN-H adducts. The signal intensity of PBN-H adducts was larger in the presence
      of 2'-dG than in the absence of 2'dG, while that of PBN-OH adducts was smaller in
      the presence of 2'-dG than in the absence of 2'-dG. When the OH-radical-induced 8
      oxodG was measured by HPLC-ECD, the yield of 8-oxodG was found to be enhanced
      about twofold in the presence of PBN. By contrast, usual OH-radical scavengers
      (DMSO, sodium formate and mannitol) inhibited the formation of 8-oxodG beyond
      expectation. The enhancement of the yield of PBN-H adducts by 2'-dG and the
      enhancement of the 8-oxodG formation by PBN were explained by the electron
      transfer and subsequent proton transfer reactions from OH-radical-induced guanine
      N7 radicals to PBN to form 8-oxodG and PBN-H. The present study led us to
      conclude that PBN reacted with the precursor radical of 8-oxodG to accelerate the
      formation of 8-oxodG, while OH-radical scavengers reacted with it to diminish the
      formation of 8-oxodG.

PMID- 9164079
TI  - Effects of 60Co gamma-rays, ultraviolet light, and mitomycin C on Halobacterium
      salinarium and Thiobacillus intermedius.
AB  - Lethal effects of 60Co gamma-rays, UV light, and mitomycin C on two kinds of
      bacteria, Halobacterium salinarium which grows in highly concentrated salt media
      and Thiobacillus intermedius which requires reduced sulfur compounds, were
      studied and compared with those on Escherichia coli B/r. D37 values for H.
      salinarium, T. intermedius and E. coli B/r were 393, 150, and 92 Gy,
      respectively, by exposure to 60Co gamma-rays. They were 212, 38, and 10 J/m2,
      respectively, by exposure to UV light and 2.36, 0.25, and 0.53 microgram/ml/h,
      respectively, by exposure to mitomycin C. Against these agents, H. salinarium was
      much more resistant than T. intermedius and E. coli B/r.

PMID- 9164080
TI  - Synthetic trehalose dicorynomycolate (S-TDCM): behavioral effects and
      radioprotection.
AB  - This study evaluated synthetic trehalose dicorynomycolate (S-TDCM), an
      immunomodulator, for its survival enhancing capacity and behavioral toxicity in
      B6D2F1 female mice. In survival experiments, mice were administered S-TDCM (25
      400 micrograms/mouse i.p.) 20-24 hr before 5.6 Gy mixed-field fission-neutron
      irradiation (n) and gamma-photon irradiation. The 30-day survival rates for mice
      treated with 100-400 micrograms/mouse S-TDCM were significantly enhanced compared
      to controls. Toxicity of S-TDCM was measured in nonirradiated mice by locomotor
      activity, food intake, water consumption, and alterations in body weight. A dose
      dependent decrease was noted in all behavioral measures in mice treated with S
      TDCM. Doses of 100 and 200 micrograms/mouse S-TDCM significantly reduced motor
      activity beginning 12 hr postinjection with recovery by 24 hr. A dose of 400
      micrograms/mouse significantly decreased activity within the first 4 hr after
      administration and returned to control levels by 32 hr following injection. Food
      and water intake were significantly depressed at doses of 200 and 400
      micrograms/mouse on the day following drug administration, and were recovered in
      24 hr. Body weight was significantly decreased in the 200 micrograms/mouse group
      for 2 days and in the 400 micrograms/mouse group for 4 days following injection.
      A dose of 100 micrograms/mouse effectively enhanced survival after fission
      neutron irradiation with no adverse effect on food consumption, water intake, or
      body weight and a minimal, short-term effect on locomotor activity.

PMID- 9164081
TI  - Multistep nature of X-ray-induced neoplastic transformation in mammalian cells:
      genetic alterations and instability.
AB  - X-ray-induced neoplastic transformation has been studied in Syrian hamster embryo
      cells. Unirradiated cells had a limited life span, whereas the irradiated cells
      escaped senescence, showed altered morphology, and acquired anchorage
      independence and tumorigenicity in a stepwise manner during successive transfers
      after irradiation. Multiple genetic changes may be associated with the expression
      of various transformed phenotypes. In fact, sequential alterations of various
      chromosomes were required for the malignant progression of irradiated cells.
      Oncogene activation was examined by the NIH3T3 transfection assay, no detectable
      changes having been identified so far. The only difference in oncogene expression
      detected was the augmented expression of the c-myc gene which was observed
      consistently. These findings indicate the multistep nature of X-ray-induced
      neoplastic transformation. Although the molecular changes involved in these
      process are still to be elucidated, recent studies have indicated that the
      instability induced by irradiation inherited through the progeny of irradiated
      cells is associated with those changes. This genetic instability provides a new
      way with which to elucidate the multistep process of radiation oncogenesis. The
      predicted mechanism and future studies are discussed.

PMID- 9164082
TI  - [Future trend in research for infectious diseases].

PMID- 9164083
TI  - [Analysis of clinical severity of tsutsugamushi disease according to the serotype
      of pathogenic rickettsia].
AB  - We compared the severity of clinical symptoms and laboratory test results of
      tsutsugamushi disease patients in Oita Prefecture according to the serotype of
      infected R. tsutsugamushi. Of the 45 patients, except one with the Karp-type, who
      were suffering in Oita Prefecture between 1992 and 1994, 20 were the Irie-type
      and 24 were the Hirano-type. There was no apparent difference with regard to
      clinical symptoms between the two groups of patients. Laboratory tests showed
      that CRP increased almost equally in the two groups. The ESR level was slightly
      higher in the Irie-type patients than in the Hirano-type, but did not differ
      significantly between the two groups. Both leukocyte count in the acute stage and
      platelet count decreased in the Hirano-type, as compared with those of normal
      ranges in the Irie-type. GPT values elevated in proportion to the day of illness
      in the acute stage. This trend continued after the initiation of specific
      chemotherapy in the Hirano-type. The median GOT, GPT and LDH values were 71, 65
      and 709 IU/l for the patients in the Hirano-type, as compared with 37, 36.5 and
      546.5 for the patients in the Irie-type, respectively. Above results show that
      the Hirano-type rickettsiae produces a more severe illness than the Irie-type
      ricketsia. Platelet count had a significant correlation with ESR, suggesting the
      pathophysiologic changes leading to disseminated intravascular coagulation, a
      symptom of severe tsutsugamushi disease. There may be common causes in leukopenia
      and thrombopenia, as being suggested by the significant correlation between
      leukocyte count and platelet count.

PMID- 9164084
TI  - [Poliovirus (Sabin strain) multiplication in human intestinal tract after oral
      polio vaccination].
AB  - Fecal specimens from a baby vaccine were collected every day from 1 to 51 days
      after primary vaccination and from 0 to 15 days after secondary vaccination.
      Polioviruses were isolated with GMK-2 cell line from 10% emulsion of the feces
      and titrated the virus contents in the emulsion of the feces. The isolated
      viruses were tested the reproductive capacity at 39.0 degrees C and 39.5 degrees
      C by the plaque method with primary cynomologous monkey kidney cells. Viruses
      were isolated from the feces during 28 days for type 1, 39 days for type 2 and 36
      days for type 3 after primary vaccination, however, only type 1 viruses were
      isolated during 7 days after secondary vaccination. The multiplication of type 3
      viruses in the intestine were increased after diminished the multiplication of
      type 1 and type 2. In plaque formation capacity at 39.0 degrees C and 39.5
      degrees C, the isolates had shown to differ clearly among the types of
      poliovirus. After primary vaccination, type 1 isolates were not produced the
      plaques at 39.0 degrees C and 39.5 degrees C. Although type 2 isolates were not
      formed the plaques until the 14th day at 39.5 degrees C, the plaque formation
      capacity of the these isolates were increased gradually i.e.; on the 20th day
      (10(0.88) PFU/ml), the 26th day (10(2.00) PFU/ml) and the 39th day (10(2.63)
      PFU/ml) at 39.5 degrees C, and all of type 2 isolates tested were showed the
      plaque formation capacity (10(2.88 approximately 10(3.76) PFU/ml) at 39.0 degrees
      C. Type 3 isolates were formed plaques at 39.0 degrees C and 39.5 degrees C from
      the 7th day. After the secondary vaccination, type 1 isolates (7th day) was a
      little changed them. Neutralizing antibody titers were shown that type 1 was 320,
      type 2 was 110 and type 3 was 60 after 1 year of the second administration. These
      titers were closely similar the geometric mean titers of 2 year old babies in
      Japan.

PMID- 9164085
TI  - [Clinical study on penicillin insusceptible/resistant Streptococcus pneumoniae in
      the elderly patients].
AB  - Clinical features of respiratory infection in the elderly with penicillin
      insusceptible (31 cases) and resistant (7 cases) Streptococcus pneumonia
      (PSSP/PRSP) are compared to those with penicillin sensitive S. pneumoniae (PSSP)
      (29 cases). Incidence of bacteremia and pneumonia was higher in the PSSP group.
      PISP/PRSP tend to be isolated from patients with bronchitis underlaid with
      chronic pulmonary disease without statistic significance. Efficacy of the
      penicillins and 1st and 2nd generation cephem was satisfactory except in only one
      case of pneumonia with PISP which needed an alternative choice to the 3rd
      generation cephem. Now a day the degree of resistance is not so high and the
      available antibiotics are sufficient for the treatment of pneumococcal infection
      in the elderly patients. However, the wide use of oral cephems and certain new
      quinolones which do not have enough activity against Streptococcus pneumoniae may
      increase resistance. In which case, continuous surveillance and clinical caution
      against this resistant strain is necessary.

PMID- 9164086
TI  - [Study of septicemia due to Enterobacter cloacae in a neonatal intensive care
      unit].
AB  - A study was made of Enterobacter cloacae septicemia in 15 newborns in the
      neonatal intensive care unit (NICU) of the Asahikawa Kosei Hospital from April,
      1979 to March, 1996. Their gestational age was 29.7 +/- 4.5 (mean +/- SD) weeks
      and their birth weight was 1,270 +/- 562 g. The age at the onset of septicemia
      was 10.3 +/- 7.2 days. Four infants died and the mortality was 26.7%. These
      infants died within 72 hours after onset of septicemia. Thrombocytopenia (<
      50,000/microliter) in the patients who died was significantly more than in the
      patients who improved (p < 0.05). Antibiotic susceptibilities were determined by
      the Kirby-Bauer method. Three E. cloacae strains isolated in 1982 were sensitive
      to ampicillin (ABPC) and cefotaxime (CTX), 4 strains between 1983 and 1984 were
      resistant to ABPC and were sensitive to CTX, 5 strains between 1985 and 1992 were
      resistant to ABPC and CTX, and 3 strains between 1993 and 1995 were resistant to
      ABPC and were sensitive to CTX. These results suggested that the emergence of
      resistant E. cloacae was related to the use of corresponding antibiotics. Our
      observations showed that E. cloacae was one of the potential pathogens seen in
      nosocomial infections which is becoming progressively common in newborns and
      routine bacteriological surveillance is very important in the NICU.

PMID- 9164087
TI  - [Genetic evaluation for rifampicin-susceptibility of Mycobacterium tuberculosis].
AB  - We evaluated the relationship between rifampicin (RFP)-susceptibility and genetic
      alterations in rpoB gene of clinically isolated Mycobacterium tuberculosis
      strains, collected from different geographic locations within Japan. Alterations
      in rpoB gene were detected by PCR-direct sequencing analysis, and the minimum
      inhibitory concentrations (MICs) of RFP were determined by broth microdilution
      method using Middlebrook 7H9 broth. One hundred and sixty six epidemiologically
      unrelated M. tuberculosis strains were examined. A total of 99 genetic
      alterations in the 69 bp core region of rpoB gene were detected in 95 out of 166
      strains. Among them, 96 out of 166 strains showed RFP-resistant phenotypes with
      MICs > or = 2 micrograms/ml. Examination of the correlation between the MICs of
      RFP and amino acid substitutions in 69 bp core region of rpoB gene revealed that
      58 out of 59 strains containing amino acid substitution in codon 531 showed
      highly RFP-resistant phenotypes with MICs > or = 64 micrograms/ml. In contrast, a
      variable level of RFP-susceptibility was observed among strains containing amino
      acid substitutions in either codon 516 or 526. On the other hand, the MICs of
      three strains with a point mutation in either codon 515 or 533 were all < or = 1
      microgram/ml. Our results suggest that rpoB gene sequencing is useful for not
      only the detection of RFP-resistant M. tuberculosis strains, but also the
      prediction of RFP-susceptibility of the strains.

PMID- 9164088
TI  - Effect of macrolide antibiotics on neutrophil function in human peripheral blood.
AB  - Since "small-dose and long-term" administration of erythromycin (EM) was shown to
      be efficacious in the treatment of chronic respiratory disease, the modulation of
      host defense responses by EM has attracted much attention. Although there is
      considerable controversy, it was recently demonstrated that EM activity reduces
      neutrophil function. In this study, we investigated the in vitro effects of the
      macrolides erythromycin (EM), a 14-membered ring, azithromycin (AZM), a 15
      membered ring and rokitamycin (RKM), a 16-membered ring macrolide, on neutrophil
      function. The DCFH-DA method and cytochrome C method were used for assay of
      active oxygen generation and the Boyden-chamber method was used for assay of
      chemotaxis. EM and AZM, both of which have been shown to be clinically effective
      in the treatment of Diffuse panbronchiolitis (DPB), significantly suppressed
      active oxygen generation and chemotaxis of neutrophils at low concentrations
      equivalent to therapeutic doses (0.5 approximately 1.0 microgram/ml, p < 0.05),
      whereas the clinically ineffective RKM did not. The in vitro inhibitory effects
      of EM and AZM on active oxygen generation and chemotaxis of neutrophils
      demonstrated in the present study may be responsible for the therapeutic efficacy
      of these 14-membered and 15-membered ring macrolides in the treatment of DPB
      patients.

PMID- 9164089
TI  - [Efficacy of erythromycin inhalation in chronic respiratory infection caused by
      Pseudomonas aeruginosa].
AB  - The prognosis of chronic respiratory tract infection with Pseudomonas aeruginosad
      considered to be poor. However, low-dose and long-term 14 membered macrolide,
      such as erythromycin or clarithromycin, treatment has been reported as effective
      clinically in chronic lower respiratory tract disease. There was no report to
      investigate the effect of macrolide on chronic biofilm related Pseudomonas
      aeruginosa respiratory tract infection in vivo. In a newly established murine
      model of chronic Pseudomonas aeruginosa respiratory infection mimicking diffuse
      panbronchiolitis (DPB), we investigated the effect of erythromcin inhalation on
      viable bacteria in the lungs. Infection was produced by placement of a plastic
      tube in the bronchus with inoculating. Pseudomonas aeruginosa suspended in saline
      was also inoculated in bronchus after intubation of the tube. Viable bacteria
      were constantly isolated at 10(4) 10(6) cfu-specimen from the lungs for more than
      30 days. Treatment with erythromycin inhalation for four days reduced the number
      of viable bacteria in the lungs with statistically significant. Our result
      indicated that our new model of chronic respiratory tract infection is simple and
      provides a useful tool to study the pathogenic process and treatment of such
      infection. Our results also suggest that the erythromycin inhalation is effective
      on chronic Pseudomons aeruginosa respiratory infection.

PMID- 9164091
TI  - [Frequency of verocytotoxin 2 (VT2) neutralizing activity in human sera].

PMID- 9164090
TI  - [Cytomegalovirus retinitis in a patient with systemic lupus erythematosus].
AB  - We report a rare case of cytomegalovirus (CMV) retinitis in association with
      systemic lupus erythematosus (SLE). A 36-year-old female was admitted to our
      hospital because of nephrotic syndrome and renal insufficiency due to lupus
      nephritis. After steroid and immunosuppressant treatment for lupus nephritis, she
      began to complain of floaters and visual disturbance. She was diagnosed as having
      CMV retinitis based upon the depressed immune status and the clinical appearance
      of fundus. As soon as CMV retinitis was diagnosed, antiviral treatment with
      intravenous ganciclovir was instituted and maintained for 7 months. She was
      treated successfully and almost no progression or relapse of CMV retinitis was
      documented without ganciclovir maintenance treatment during a 2 year follow-up
      period. It is suggested that CMV retinitis can occur in patients with SLE treated
      with steroid and immunosuppressant, indicating the importance of early diagnosis
      and treatment for CMV retinitis.

PMID- 9164092
TI  - Freedom of choice ... at a price.

PMID- 9164093
TI  - Introspection in the house of medicine.

PMID- 9164094
TI  - Physicians give MMA high ratings.

PMID- 9164095
TI  - Alcohol use in Minnesota. Extent and cost.

PMID- 9164096
TI  - MMA calls for fair Medicare reimbursement.

PMID- 9164097
TI  - Seizures and spells: physician awareness of Minnesota driving laws.
AB  - Personal physicians are the primary source of information about state driving
      regulations for individuals with episodic disturbances of neurologic function
      (e.g., epilepsy, syncope, hypoglycemia). However, a May 1994 survey of Twin
      Cities metro-area neurologists and a sample of family practice physicians
      statewide revealed that many Minnesota physicians are unfamiliar with the
      relevant laws, and what knowledge doctors have of these laws is influenced by
      their specialties. Some physicians thought the regulations were more restrictive
      than they actually are, some less. Even physicians familiar with the laws didn't
      know which spells should be reported.

PMID- 9164098
TI  - Is direct contracting the business of insurance?

PMID- 9164099
TI  - Autre temps, autre moeurs.

PMID- 9164100
TI  - Interview with Mark Aita, MD, SJ. Interview by Robin K. Levinson.

PMID- 9164101
TI  - Whither managed care?

PMID- 9164102
TI  - Simplified vaginal hysterectomy: a pioneer approach.

PMID- 9164103
TI  - Can we manage pain?

PMID- 9164104
TI  - A tale of two New Jersey cities.
AB  - Judging from the social and health measures considered in this article, Newark
      and Jersey City face similar challenges as other large cities. For Newark, the
      challenges are more extreme. The high rates of poverty and violence, coupled with
      a low rate of high school graduation and a large number of single parent
      households bode ill for the city. The hospitals in Newark and Jersey City have
      undergone major changes in meeting the needs of their communities. They have
      adjusted their size, shortened their lengths of stay, and provided more intensive
      care services and outpatient services. Of special concern for New Jersey's
      hospitals is the reliance on Medicaid financing. If dramatic changes are made to
      the Medicaid program, Newark hospitals should be on high alert. Legislatures need
      to tread carefully in designing policies that address the needs of New Jersey's
      large cities. The state is undergoing major changes in its health care system.
      The demise of the all-payer rate setting system, the establishment of the Health
      Care Subsidy Fund to finance uncompensated care and subsidize insurance for low
      and middle-income families, modifications to the community rating system for
      private insurance, and changes to the welfare system that affect eligibility for
      Medicaid all require legislators to consider the context in which these programs
      operate.

PMID- 9164105
TI  - Care and caring at the end of life.

PMID- 9164106
TI  - Organ transplantation research initiatives in New Jersey.

PMID- 9164107
TI  - Economic credentialing and exclusive contracts.

PMID- 9164108
TI  - Restrictive covenants in a physician's employment agreement.

PMID- 9164109
TI  - Innovations at Deborah Heart and Lung Center.

PMID- 9164110
TI  - [Evaluation of hepatic encephalopathy and portal hemodynamics by Doppler
      ultrasonography after a transjugular intrahepatic portosystemic shunt].
AB  - TIPS (transjugular intrahepatic portosystemic shunt) is an efficacious treatment
      for esophagogastric varices, ascites and hypertensive gastrointestinal
      vasculopathy associated with portal hypertension. The main complication after the
      procedure is hepatic encephalopathy. We tried to elucidate the correlation
      between hepatic encephalopathy and changes in portal hemodynamics after TIPS,
      based on observation by Doppler ultrasonography. We carried out Doppler
      ultrasonography in 28 cases of TIPS to assess hepatopetal and hepatofugal blood
      flow in the right and left portal branches. Hepatic encephalopathy occurred after
      TIPS in 9 cases out of 28 (32%), and new onset of disease was observed in 6 of 9.
      Doppler ultrasonography revealed hepatofugal blood flow in both right and left
      portal branches in 6 cases, 5 of which showed encephalopathy. Hepatopetal blood
      flow of the right and left portal branches was observed in 17 of 28 cases after
      TIPS. Hepatic encephalopathy occurred in only 2 of 17 cases. The changes in
      portal vein hemodynamics after TIPS were investigated by color Doppler
      ultrasonography, which were considered to be very useful for prediction of
      hepatic encephalopathy and indication of medical treatment to prevent the
      occurrence of this disease.

PMID- 9164112
TI  - [Evaluation by MR imaging of the velocity and volume of pre- and postprandial
      portal blood flow in the presence or absence of liver cirrhosis].
AB  - PURPOSE: We measured pre- and postprandial changes in the portal flow of normal
      volunteers and patients with liver cirrhosis using MR imaging and examined how to
      quantify portal flow to evaluate liver function. MATERIALS AND METHODS: Three
      groups were selected: middle aged normal volunteers (mean age 37.2 yrs., 5
      persons), aged normal volunteers (mean age 61.5 yrs., 6 persons), and patients
      (mean age 67.6 yrs., 7 persons). We used cine-PC and the spin-echo method to
      measure portal flow velocity (PV) and vertical sectional area (PA), respectively.
      We repeated measurements of PV and PA in turn for about 60 minutes after a meal.
      RESULT: There were no significant differences in PV between the three groups
      before the meal. Study after the meal also indicated no significant difference
      between the two normal groups. In the normal group, PV and portal flow volume
      (Pvol.) increased by about 77% and 127%, respectively. In the cirrhotic liver
      group, PV and Pvol. increased by about 14% and 32%, respectively. A significant
      difference was seen between the normal and patient groups after the meal. We,
      therefore considered that the changing rate of Pvol. might be a sensitive
      parameter for evaluating liver function, including reserve.

PMID- 9164111
TI  - [In vivo evaluation of the new antithrombogenic reservoir-catheter coated with
      polymer blend copolymer].
AB  - We evaluated the antithrombogenicity of 4F-catheters coated with the new
      antithrombogenic material fluorine-acryl- styrene-urethane-silicone (FASUS) graft
      block copolymer by dissecting microscopic and scanning electron microscopic
      observations. These catheters were temporarily used for the infusa-A-port, which
      was prepared for the treatment of four patients with bladder cancer. Two heparin
      coated catheters were also evaluated. All FASUS-coated catheters contained
      thrombi consisting of red thrombi and/or fibrin thrombi. Massive red thrombus was
      seen at the site of curvature of the catheters, 1 cm distal to the tip of the
      catheter. However, the portion 20 cm distal to the tip of the catheter had no red
      thrombus, but contained minimal fibrin thrombus or plasma protein. The heparin
      coated catheters showed the same findings as the FASUS catheters. The FASUS
      coated catheters were not superior in antithrombogenicity to the heparin-coated
      catheters. It was concluded that the FASUS-coated catheters used in this study
      seemed to have problems in regard to their preshaped curvature and the material
      used in catheter. These aspects need to be improved.

PMID- 9164113
TI  - [Usefulness of helical DIC-CT in pancreaticobiliary maljunction].
AB  - [PURPOSE]: To determine the usefulness of helical CT during drip infusion
      cholangiography (DIC-CT in patients with pancreaticobiliary maljunction.
      [MATERIALS AND METHODS]: DIC-CT was performed in six patients with
      pancreaticobiliary maljunction. After drip infusion of 100 ml of Iotroxic acid
      meglumine, helical CT was performed. One mm or 1.5 mm interval images were
      reformatted from the raw data. Thereafter, multi-plannar reconstruction (MPR)
      images were obtained from the reformatted images. The reformatted images and the
      MPR images were reviewed. [RESULTS]: In all cases, the form of the union was
      visualized. In two patients, a contrast defect was shown in the common bile duct
      arising from the union of the pancreatic duct. The defects were considered due to
      pancreatic juice reflux into the common bile duct. In the other two patients, the
      contrast medium in the common bile ducts was regurgitated into the pancreatic
      duct. [CONCLUSION]: DIC-CT was very useful in the evaluation of
      pancreaticobiliary maljunction, because of its functional characteristics, high
      resolution and three-dimensional data.

PMID- 9164114
TI  - [Proton MR spectroscopy of hyperplastic hematopoietic marrow in aplastic anemia].
AB  - The purpose of this study was to compare the findings of magnetic resonance (MR)
      spectroscopy of hyperplastic hematopoietic marrow with those of normal bone
      marrow. Twenty-four samples of normal marrow from eight control subjects and 19
      samples of hyperplastic marrow in aplastic anemia were examined with a 1.5T MR
      unit. The former showed low intensity on opposed-phase T1-weighted images, while
      the latter showed high intensity on both fast STIR and opposed-phase T1-weighted
      images. MR spectroscopy quantitatively confirmed that the water: fat ratio was
      increased and the transverse relaxation time of water was changed in hyperplastic
      bone marrow, compared with normal bone marrow. In summary, MR imaging is able to
      detect hematopoietic regions among a wide range of bone marrow of aplastic
      anemia, while MR spectroscopy allowed us to quantitatively analyze the cell
      population of hyperplastic hematopoietic marrow in aplastic anemia.

PMID- 9164115
TI  - [Usefulness of chest CT in diagnosing pneumonia].
AB  - The usefulness of chest CT in diagnosing pneumonia was evaluated by a
      retrospective review of 110 pneumonia cases in which both plain chest radiograph
      and CT were obtained. Detection of abnormal opacities on chest radiograph was
      difficult or impossible in 9 cases (8.2%), requiring CT to detect them. The
      opacities which appeared consolidative, nodular, small nodular or cavitary on
      chest radiograph were shown as opacities of similar character on CT. On the other
      hand, many opacities of patchy, ground-glass or linear/reticular character on
      chest radiograph were shown as opacities of different character on CT. One case
      out of 3 of mycoplasma pneumonia, one case each of influenza viral pneumonia and
      pneumocystis carinii pneumonia and showed rather typical appearance on CT.
      Detection of pleural effusion on chest radiograph was difficult in 17 (58.6%) of
      29 cases in which it was easily detected on CT. In conclusion, CT is useful in
      diagnosing pneumonia in limited cases, as follows: (1) indistinct abnormal
      opacity on chest radiograph despite positive clinical signs of pneumonia, (2)
      patchy, ground-glass or linear/reticular opacities on chest radiograph, (3)
      confirmation of pleural effusion, (4) close observation of sequential changes of
      opacity after starting treatment of pneumonia. In contrast, CT is not generally
      useful in evaluating consolidative opacities on chest radiograph.

PMID- 9164116
TI  - [Comparison of calculated and measured rectal doses in HDR brachytherapy with Ir
      192 source].
AB  - Two orthogonal radiographs are used to reconstruct the three-dimensional
      positions of applicators (sources) and their dosemeter for assessing afterloading
      techniques. It has always been assumed that the applicators are perfectly fixed
      and unchanged during irradiation. In a review comparing measurements by a five
      detector dosemeter and calculated doses in our institution, a relatively poor
      correlation (correlation coefficient = 0.79) was observed. The purpose of this
      study was to investigate the sources of this difference between calculated and
      measured rectal doses in HDR brachytherapy with Ir-192 source. In this study, the
      calculated dose was used as a reference value. The overall percentage difference
      between calculated and measured rectal doses was estimated at 9%. The major
      source of the difference between calculated and measured rectal doses was
      applicators and dosemeter movement during irradiation. This was verified by X-ray
      fluoroscopy during irradiation. It was found that loose fastening of the
      applicators caused a change in the position of the applicators and dosemeter
      during irradiation. By improving the fastening of the applicators and dosemeter,
      the correlation (correlation coefficient = 0.90) between calculated and measured
      doses was improved. The results demonstrate the importance of the fastening of
      the applicators and dosemeter.

PMID- 9164117
TI  - [Application of diffusion-weighted echo planar imaging for diagnosis of small
      acute and subacute brain ischemic lesions].
AB  - The aim of this study was to determine the utility of diffusion-weighted echo
      planar imaging (DW-EPI) for detecting acute and subacute brain ischemic foci less
      than 2 cm in size. Thirty patients underwent DW-EPI on a 1.5 T superconducting
      unit using a SE-EPI sequence with an arbitrary pair of Stejskal-Tanner gradients
      applied along the imaging axes. DW-EPI demonstrated all the mast recent ischemic
      lesions as areas of decreased diffusion, providing greater conspicuity and larger
      size than conventional spin-echo imaging. DW-EPI is a promising method to detect
      within a subsecond early ischemia and reversible ischemic changes that are not
      demonstrate on routine spin-echo images.

PMID- 9164118
TI  - [Effect of glucose-insulin infusion on thallium-201 chloride tumor imaging].
AB  - Thallium-201 chloride (201Tl) kinetics, may be affected by serum insulin levels
      like potassium kinetics. The purpose of the present study was to use glucose and
      insulin to improve 201Tl accumulation in the tumor. The results showed that the
      tumor-to-normal tissue ratio after simultaneous injection of 201Tl, glucose and
      insulin was significantly higher than that after the injection of only 201Tl, and
      that a ring appearance seemed to occur after glucose and insulin injection. This
      preliminary study suggests that 201Tl accumulation in the tumor is enhanced by
      glucose and insulin administration.

PMID- 9164119
TI  - [MR spectroscopy in acute brain infarction: differentiation of infarcted and non
      infarcted areas].
AB  - Two cases of brain infarction were studied using multivoxel proton MR
      spectroscopy (MRS). MRS of both cases clearly demonstrated an increased level of
      lactate and decreased N-acetylaspartate (NAA), resulting in a high lactate/NAA
      ratio (LNR). Case 1 without thrombolysis therapy revealed that the area where LNR
      was less than 1.0 did not develop to infarction. This was also confirmed by MRS
      of case 2, who received an interventional reperfusion 4 hours after onset. In
      acute stags of brain infarction, on LNR greater than 1.0 on H-MRS may predict the
      margin of the infarcted region. Elevation of lactate in the non-infarcted
      cerebral hemisphere has not been reported before, and farther evaluation is
      necessary.

PMID- 9164120
TI  - [A case of retained surgical sponge penetrated into the sigmoid colon].
AB  - A thread of surgical sponge was found by colonoscopy at the sigmoid colon wall in
      the tip of a granuloma. The patient was a 50-year-old woman who complained of
      diarrhea and had a history of Cesarean section and complete hysterectomy. A
      radiopaque thread that used to be part of the surgical sponge was demonstrated
      with plain pelvic X-ray films. Abdominal CT study revealed the gossypibioma
      including a radiopaque thread in front of the sacrum. The patient was admitted
      for endoscopic extraction. Upon endoscopic observation, no thread was found and
      the fistula had also disappeared. The surgical sponge was considered to have been
      spontaneously expelled from the fistula during the intervening 22-day period.

PMID- 9164121
TI  - [Tumor seeding to the neck through percutaneous applicators of interstitial high
      dose-rate brachytherapy for cancer of the tongue: a case report].
AB  - We report the case of a 46-year-old woman with cancer of the tongue. She
      underwent interstitial high-dose-rate brachytherapy of 50 Gy in 10 fractions for
      5 days following telecobalt therapy of 20 Gy in 10 fractions for 2 weeks. Seven
      applicators were percutaneously implanted into the tongue. Radical neck
      dissection was carried out because a tumor rapidly developed on the neck 2.5
      months after the treatment. Pathological examination revealed tumor seeding to
      the soft tissue of the neck where applicators were placed. To the best of our
      knowledge, there have been no reports presenting tumor seeding through
      percutaneous applicators of interstitial brachytherapy for head and neck tumor.

PMID- 9164122
TI  - [The 40th annual meeting of the Japanese Society of Nephrology. Niigata City,
      Japan. May 14-16, 1997. Abstracts].

PMID- 9164123
TI  - Wanted: retired physicians to serve as medical examiners.

PMID- 9164124
TI  - Costs and consequences of ESRD in NC.

PMID- 9164125
TI  - Medical school's role in roundtable discussion.

PMID- 9164126
TI  - The prevalence of cancer in North Carolina.

PMID- 9164127
TI  - Should we test women for inherited susceptibility to breast cancer? what do NC
      primary care physicians think.

PMID- 9164128
TI  - Taking sides. Can we reach middle ground in a managed care system?

PMID- 9164129
TI  - Nutrition and Parkinson's disease.

PMID- 9164130
TI  - Use of bicycle helmets by Greensboro children.

PMID- 9164131
TI  - Living with hypertension. Introduction to dealing with elevated blood pressure.
AB  - Gaining control of hypertension requires a large effort on the part of not only
      the patient and physician, but other health care providers as well. Successful
      hypertension management is defined as lowering blood pressure to less than 140
      millimeters of mercury systolic and less than 90 millimeters of mercury
      diastolic. If blood pressure is lowered gradually, one can expect to feel better.
      In most situations, there is no benefit in rapidly lowering blood pressure. The
      down side of rapid blood pressure lowering is that individuals tend to feel bad,
      at least temporarily, and are likely to discontinue medication. Patience is the
      key. It takes at least four to six weeks to achieve normal blood pressure when a
      new medication is started. Almost all of the blood-pressure medications work
      better when the individual makes lifestyle changes (loses weight, reduces salt
      and alcohol intake, and increases aerobic activity).

PMID- 9164132
TI  - Health care in ancient Rome. Lessons for doctors today.

PMID- 9164133
TI  - United Medical Research Foundation. A brief chapter in the history of North
      Carolina medicine.

PMID- 9164134
TI  - Bronchoscopic evaluation of pediatric airway pathology.

PMID- 9164135
TI  - Ultrapulse CO2 laser resurfacing. Treatment for wrinkled, photodamaged skin.

PMID- 9164136
TI  - [The skin vasomotor dysfunction of the juvenile muscular atrophy of the distal
      upper limb--investigation by the ice water immersion test].
AB  - We investigated the skin vasomotor function of the juvenile muscular atrophy of
      the distal upper limb (JMA) by the ice water immersion test. The skin temperature
      of the bilateral second fingers during ice water immersion were measured in 17
      patients with JMA and 25 normal controls. The insufficient fall of the skin
      temperature during ice water immersion was observed in 5 patients (3 patients in
      atrophic side, 2 patients in non-atrophic side). The insufficient recovery of the
      skin temperature was observed in 6 patients (3 patients in atrophic side, 3
      patients in non-atrophic side). The both of the insufficient fall and recovery of
      the skin temperature was observed in one patient (both sides). The insufficient
      fall of the skin temperature indicates the hypofunction of skin vasomotor
      activity, and the insufficient recovery of the skin temperature indicates the
      hyperfunction of skin vasomotor activity because JMA has no disturbance of the
      peripheral sensory nerve fibers. We conclude that the responsible lesion of these
      abnormalities may be in the descending sympathetic tract in the cervical spinal
      cord.

PMID- 9164137
TI  - [The effects of spinal fusion on respiratory function and quality of life in
      Duchenne muscular dystrophy].
AB  - We studied the functional outcome of spinal fusion for the surgical treatment of
      scoliosis in 8 patients with Duchenne muscular dystrophy (DMD). The mean age of
      DMD patients at the time of the surgery and the mean follow-up duration was 13.8
      (12.3 to 15.4) and 3.9 (1.5 to 6.8) years, respectively. The average spinal angle
      (Cobb angle) was corrected from 58.8 to 28.6 degrees with the mean corrective
      rate of 51.3% by the surgical intervention. The correction rate was higher and
      the corrected Cobb angle remained unchanged during follow-up period in mildly
      scoliotic patients. Forced vital capacity (FVC) increased post-operatively in 3
      patients with moderate scoliosis (Cobb angle: 50 to 80 degrees), indicating that
      the correction of spinal alignment is effective for the treatment of decreased
      thoracic volume in DMD. On the other hand, two cases with low % FVC (16.9% and
      30.4%, respectively) had poor prognosis in respiratory status. Namely, one died
      of pneumonia at 17 months after the surgery and the other required mechanical
      ventilation via nasal mask at 3 years post surgery. Sitting balance improved in
      all patients, which resulted in more functional use of their upper extremities.
      During the follow-up period, all patients except one patient who died of
      pneumonia could maintain sitting balance without support. Moreover these included
      2 patients over 20 year old. No complications related to spinal deformities have
      been found in these patients. Previous study in our hospital showed that 7 of 48
      (14.6%) of DMD patients spent all their lives without apparent scoliosis (Cobb
      angle less than 30 degrees). These suggest that spinal fusion could be
      recommended for patients with Cobb angle more than 30 degrees and with % FVC more
      than 35%. Although the impact of spinal fusion upon the life expectancy remains
      unclear, favorable effect on respiratory function and quality of life can be
      expected for carefully selected patients with DMD.

PMID- 9164138
TI  - [A nationwide survey on paraneoplastic neurological syndromes. Project group on
      paraneoplastic neurological syndromes, Neuroimmunological Disease Research
      Committee, the Ministry of Health and Welfare, Japan].
AB  - A nationwide survey on paraneoplastic neurological syndrome was carried out using
      enquiry sheets for neurologists in hospitals to examine the approximate number of
      patients, clinical features, characteristic anti-neuronal antibodies,
      accompanying malignancy and current therapies of these syndromes. In the present
      survey, 159 case records of this syndrome were accumulated. The major clinical
      variations were as follows: sensory neuropathy (54 cases; 34%), Lambert-Eaton
      myasthenic syndrome (45 cases; 28%) including 5 cases complicated with subacute
      cerebellar degeneration (PCD), PCD (40 cases; 25%) and limbic encephalitis (8
      cases; 5%). Neurological symptoms preceded diagnosis of malignancy in over 83% of
      the total cases of these four major clinical variations in which tumors were
      verified. The detection of anti-neuronal antibodies, which are characteristic of
      some clinical types of this syndrome, is very important for early diagnosis and
      treatment for the neurological symptoms and underlying malignancy.

PMID- 9164139
TI  - [Abnormally distributed regional cerebral blood flow in brain malformations
      detected by single photon emission computed tomography].
AB  - Brain malformations are rare congenital anomalies caused by neuronal migration
      disorders or cerebral tissue destruction during gestation. And epileptic
      disorders and psychomotor retardation are sometimes induced by them. Previous
      understanding of these anomalies was derived from pathologic studies after
      autopsy. The recent advancement of neuroimaging techniques, such as magnetic
      resonance imaging (MRI), has allowed us to achieve a high diagnostic capability
      of these malformations. These abnormalities have been more widely recognized
      morphologically. However, cerebral function in these cases has been rarely
      described. To evaluate the cerebral functional state in these anomalies, 123I-N
      isopropyl-p-iodoamphetamine (123I-IMP) single photon emission computed tomography
      (SPECT) was performed in 3 cases with brain malformations and 22 normal controls.
      Several regions of interest (ROI) in the cortex were determined, and the
      radioactivity at each ROI was counted. The regional cerebral blood flow (rCBF)
      distribution was evaluated semiquantitatively by calculating the cortico
      cerebellar ratios at each ROI. A 23-year-old female with schizencephaly (Case-1)
      and a 21-year-old male (Case-2) with polymicrogyria showed increased rCBF in
      their abnormal cortices. And a 39-year-old male with porencephaly (Case-3)
      demonstrated severely decreased rCBF in his abnormal cortex with gliosis which
      was considered to be a result from a secondarily disturbed neuronal migration
      after tissue destruction during gestation. Furthermore, abnormal rCBF
      distribution was observed in their morphologically normal cortices in addition to
      their abnormal cortices compared to normal controls. Case-2 showed decreased
      cerebral perfusion in the morphologically normal cortex around his abnormal
      cortex with increased rCBF, suggesting surrounding suppression associated with
      epileptic foci. In contrast, the lesions with decreased rCBF in Case-1 were not
      around the abnormal cortices. In the cortices with decreased rCBF, despite
      morphologically normal imaging, of Case-3, the decrement was considered to be
      diaschisis, since these lesions were located in the ipsilateral hemisphere of the
      tissue defect. We concluded that brain malformations show various rCBF
      abnormalities, and these are spread over a larger area than detected by MRI.
      Therefore, SPECT is a valuable examination method for the determination of
      abnormal areas and the assessment of pathologic functional state in patients with
      brain malformations.

PMID- 9164141
TI  - [A case of myasthenia gravis associated with systemic lupus erythematosus and
      pemphigus erythematosus].
AB  - A 34-year-old woman was admitted to our hospital because of ptosis, dysarthria,
      muscle weakness of upper limbs and skin lesions. At the age of 22 years, she was
      diagnosed as having systemic lupus erythematosus (SLE) due to the presence of
      arthritis and high titer of antinuclear antibody. On admission, the high
      antiacetylcholine receptor antibody titer, along with the positive tensilon test
      and electromyography established a diagnosis of myasthenia gravis (MG). The
      demonstration of anti-intercellular antibodies both in cutaneous tissue and blood
      confirmed the diagnosis of pemphigus. MRI showed hypertrophic thymus. After
      thymectomy, the myasthenic symptoms aggravated and SLE and pemphigus
      erythematosus relapsed despite anti-cholinesterase treatment with plasmapheresis.
      She was then placed on corticosteroid therapy with an improvement of her all
      symptoms. This very rare case of MG associated with SLE and pemphigus
      erythematosus suggests that these diseases share common immunological
      abnormalities.

PMID- 9164140
TI  - [Guillain-Barre syndrome with high titers of anti-GM2 and anti-GalNAc-GD1a
      antibody following cytomegalovirus hepatitis].
AB  - A 28-year-old housewife developed motor and sensory neuropathy in both limbs with
      facial nerve paralysis and decreased taste sensation, two weeks after cough and
      sore throat with slight fever. On laboratory examination, mild increase of
      transaminases was found. Enzyme-linked immunosorbent assay showed that the serum
      had markedly high titers of IgG antibodies to GM2 (1:3,200) and Ga1NAc-GD1a
      (1:1,600). Serum IgM-EIA index and CF titer of cytomegalovirus were markedly
      high. In cerebrospinal fluid examination, protein was increased (110 mg/dl).
      Blink reflex indicated involvement of bilateral facial nerves. In limb motor and
      sensory nerves, conduction studies revealed the presence of both axonal
      degeneration and segmental demyelination. The diagnosis of Guillain-Barre
      syndrome (GBS) with facial nerve paralysis, relatively unique to CMV infection,
      was made. In the fourth week following the initial neurologic symptom, weakness
      in facial and limb muscles and sensory disturbances in both limbs were gradually
      improved. In about three months, conduction studies of limb nerves and CSF
      protein were normalized. During the clinical course above, the titers of
      antibodies to GM2 and Ga1NAc-GD1a, IgM-EIA index and the titer of CF of CMV were
      significantly decreased. Anti-GM2 antibody was reported to be found in the sera
      from the patient of GBS associated with CMV infection. However, there is no
      report of GBS patient with CMV infection whose serum showed the presence of both
      anti-GM2 and anti-Ga1NAc-GD1a antibodies. In this patient, antibodies to CMV, GM2
      and Ga1NAc-GD1a epitopes and other unexamined or/and unknown epitopes may be
      related to the neuropathy. The studies of the specific antibody to react with
      facial nerve in the serum from GBS patients with facial nerve paralysis and the
      molecular mimicry between the specific ganglioside and the structure of CMV are
      warranted in future.

PMID- 9164142
TI  - [A case of allergic granulomatous angitis with beneficial effects of plasma
      exchange].
AB  - A 54-year-old man had suffered from bronchial asthma, followed by numbness and
      muscle weakness of the extremities. He was admitted to our department in July,
      1994, because of progression of the symptoms. On admission, neurological
      examination revealed muscle weakness with atrophy and sensory disturbance of
      multiple mononeuritic type. Blood tests revealed eosinophilia and an increase in
      rheumatoid factor, IgE levels and P-ANCA. A sural nerve biopsy showed necrotizing
      vasculitis and inflammation with eosinophil infiltration. The patient was
      diagnosed as having allergic granulomatous angitis,and treated with steroid pulse
      therapy without beneficial effect. Plasma exchange was performed twice, which
      resulted in remarkable improvement in motor and sensory disturbance. The present
      case suggests that plasma exchange has beneficial effects on severe cases with
      allergic granulomatous angitis.

PMID- 9164143
TI  - [Axonal Guillain-Barre syndrome associated with antibodies to Ga1NAc-GD1a and
      unidentified acidic glycolipids].
AB  - A 19-year-old male student with Guillain-Barre syndrome (GBS) was described.
      Neurologic examination revealed severe and moderate degrees of weakness in the
      distal and proximal muscles, respectively, in both upper and lower limbs. He was
      unable to walk even with support. Both superficial and deep sensations were
      normal. Serial electrophysiologic studies indicated that the predominant
      pathologic process of the peripheral nerve was axonal degeneration of motor
      nerves. Enzyme-linked immunosorbent assay showed that serum from the patient had
      markedly high titer of IgG antibody to Ga1NAc-GD1a (1:204,800). Thin-layer
      chromatography with immunostaining revealed that his serum IgG strongly reacted
      with Ga1NAc-GD1a prepared from both bovine brain and cauda equina, and
      additionally with unidentified acidic glycolipids prepared only from bovine cauda
      equina. Serum containing antibody to Ga1 NAc-GD1a and the unidentified acidic
      glycolipids may be responsible for axonal degeneration of motor nerves in this
      patient.

PMID- 9164144
TI  - [A case of severe involvement of the motor neuron system accompanied with
      cerebellar ataxia].
AB  - Here we report a sporadic case of severe involvement of the motor neuron system
      accompanied with cerebellar ataxia. A 55-year-old Japanese woman was admitted to
      our hospital because of unstable gait and clumsiness of hands. Since she had
      prominent ataxia, she was initially diagnosed as late onset cortical cerebellar
      atrophy (LCCA). However, mild muscular weakness and atrophy were pointed out.
      Weakness in extremities progressed slowly and she became unable to walk in two
      years. On the second admission, in addition to cerebellar ataxia, she had
      moderate to severe muscular weakness and atrophy with fasciculation in
      extremities. Although she had no sensory impairment, micturitional disturbance
      nor orthostatic hypotension, she had impaired skin sweating response. MRI imaging
      revealed moderate cerebellar and brain stem atrophy. Neurophysiological
      examination revealed upper and lower motor neuron damage. Beta-D-N
      acetylglucosaminidase activity was normal and SCA1, DRPLA and Machado-Joseph
      disease were excluded by DNA studies. Combination of motor neuron disease and
      cerebellar degeneration has been very rare. Only two cases similar to our case
      were reported before. Our patient had anti GM1-ganglioside antibody in her serum,
      suggesting that motor neuron disease and cerebellar degeneration may occur with
      the same pathophysiological mechanism.

PMID- 9164145
TI  - [A family with dentato-rubro-pallido-luysian atrophy (DRPLA): an
      intergenerational contraction of the CAG repeat].
AB  - We describe the relation of the CAG repeat length to the genetic anticipation in
      a Japanese family with dentato-rubro-pallido-luysian atrophy (DRPLA). The
      proband, a 21-year-old woman, developed epilepsy at age 19. Her mother has
      displayed cerebellar ataxia, choreoathetosis, and dementia since age 40, and the
      grandmother has shown cerebellar ataxia since age 52. So a genetic anticipation
      was observed. The CAG repeat sizes of peripheral blood lymphocytes from the
      proband, mother, and grandmother were found to be 61, 59, and 60, respectively.
      Thus, the mother showed earlier onset but a smaller CAG repeat length as compared
      to the grandmother. This case is thought to be rare and valuable in respect that
      the intergenerational contraction of the CAG repeat was shown in spite of the
      genetic anticipation was observed.

PMID- 9164147
TI  - [Myelopathy due to vitamin B12 deficiency presenting only sensory disturbances in
      upper extremities: a case report].
AB  - We report a 54-year-old man with vitamin B12 deficiency myelopathy limited to the
      upper extremity region. He was well until October, 1995, when he had an onset of
      exertional dyspnea and general fatigue. Then he noted tingling sensation in
      bilateral upper extremities in March, 1996. He had undergone total gastrectomy
      due to gastric ulcer 15 years ago. Neurological examination revealed superficial
      and vibratory sensory loss in the upper extremities distal to elbows, and
      pseudoathetoid movement of the left fingers. Otherwise neurological examination
      was unremarkable. Laboratory examination revealed macrocytic anemia, and low
      serum vitamin B12. However, serum folate was within the normal range. In SEP
      studies, median nerve stimulation evoked peripheral N9 and N13 potentials, but
      not cortical N20 one. Posterior tibial nerve stimulation elicited normal
      responses. MEP, VEP, needle EMG, and nerve conduction studies gave normal
      findings. T2-weighted MRI showed high signal intensity lesions at the C1-Th1
      level in the posterior column, especially in the cuneate fascicles. The gracile
      fascicles were spared. This is a very rare case of myelopathy due to vitamin B12
      deficiency presenting only sensory disturbances in both upper extremities. The
      lesions limited in the cuneate fascicle were confirmed by electrophysiological,
      and neuroradiological examinations.

PMID- 9164146
TI  - [Brain embolism associated with atrial septal aneurysm].
AB  - We studied the clinical significance of atrial septal aneurysm on brain embolism.
      Of two-hundred twenty-eight consecutive ischemic stroke patients, 128 cases were
      performed transesophageal echocardiography to find cardiac lesions that could be
      embolic sources. Three cases were diagnosed as having atrial septal aneurysm with
      right-to-left shunt demonstrated by contrast echocardiography under Valsalva
      maneuver. These cases were all diagnosed as brain embolism from clinical courses
      and findings from brain CT scan, and cerebral angiography. Neurosonologic study,
      24 hours Holter ECG, and transthoracic echocardiography did not reveal any other
      embolic sources. Paradoxical embolic mechanism is supposed to have occurred in
      these cases. Atrial septal aneurysm often coexists with right-to-left shunt and
      is clinically significant as a finding suggesting paradoxical embolism.

PMID- 9164148
TI  - Guidelines on training and credentialling for the the practice of minimal access
      surgery (MAS). Recommendations of the South African Society of Endoscopic
      Surgeons (SASES).

PMID- 9164149
TI  - Liver trauma in 446 patients.
AB  - A total of 446 patients with liver trauma were treated over a 10-year period: 295
      (66%) had penetrating injuries (204 stab wounds, 91 gunshot wounds) and 151 (34%)
      blunt trauma. Seventeen patients died during resuscitation before laparotomy. In
      344 (80%) of the 429 patients who underwent laparotomy, injuries were managed by
      simple methods such as temporary packing, diathermy, sutures or vessel ligation.
      Eighty-five patients (18%) had complex injuries and underwent one or more of the
      following procedures to control bleeding: hepatotomy and intrahepatic vessel
      suture (28), resectional debridement (31), lobar resection (17), perihepatic
      packing and relaparotomy (25), total hepatic isolation (4) or atriocaval shunt
      (1). Overall mortality was 54 (12.1%) and was greatest after blunt injury (27%)
      compared with gunshot (11%) and stab wounds (2%). Mortality was directly
      attributable to the abdominal injury in 39 patients, 22 of whom died from
      uncontrolled haemorrhage. Complications occurred in 151 of 392 survivors (38.5%)
      and correlated with type and severity of the liver injury (31% in stab wounds,
      43% in gunshot wounds, 57% in blunt injuries) and the number of associated
      injuries. As many as 80% of liver injuries can be managed by simple surgical
      techniques. In major liver injuries perihepatic packing may be life-saving,
      allowing control of bleeding before a logical sequential strategy is instituted
      to isolate and repair the injury.

PMID- 9164150
TI  - Pitfalls in the prediction of renal function in the intensive care unit. A
      review.

PMID- 9164151
TI  - Measurements of glomerular filtration in the intensive care unit are only a rough
      guide to renal function.
AB  - An estimate of glomerular filtration rate (GFR) is important in intensive care
      units (ICUs) to individualize drug dosages, and for the early detection of acute
      renal failure (ARF). Creatinine clearance or calculations based on plasma
      creatinine are the most widely used indicators of GFR, but may be very inaccurate
      in critically ill patients. We have assessed the accuracy of predictions of GFR
      by creatinine clearance and plasma creatinine in critically ill patients with
      variable creatinine kinetics. This is a retrospective record review set in a 24
      bed multidisciplinary ICU. Eighteen patient records (9 normal renal function, 9
      with ARF-250 patient days) were evaluated. Creatinine clearance measured daily
      over an 8-hour period, plasma creatinine, creatinine production and 8-hourly
      urine output were recorded for each day of ICU stay. The discrepancy between
      measured creatinine clearance and creatinine clearance predicted by the Cockcraft
      Gault equation was determined. The coefficient of variation (CV) for each of the
      contributing variables and the final inherent error for the estimation of GFR
      were determined. The difference between measured and predicted creatinine
      clearance was large (predicted GFR may be from 60 ml/min above to 70 ml/min below
      measured creatinine clearance). The mean CV for creatinine production was 28% and
      for 8-hourly urine output it was 34%. The estimation of GFR from creatinine
      clearance can be made at +/- 52% of the calculated value, whereas the estimation
      of GFR by Cockcraft-Gault is accurate at +/- 37% of the calculated value.
      Unstable creatinine kinetics from variable urine output and creatinine production
      in critically ill patients make accurate estimation of GFR impossible. While
      prediction methods have fewer inherent sources of error, plasma creatinine may be
      influenced by factors other than renal function. The use of prediction equations
      is as inaccurate as measured clearance in unstable ICU patients.

PMID- 9164152
TI  - Haemodynamic response to tracheal intubation or laryngeal mask insertion in
      hypertensive patients.
AB  - The haemodynamic response to laryngeal mask insertion and tracheal intubation was
      studied in 27 hypertensive patients who underwent elective ophthalmic surgery.
      Both groups received alfentanil 15 micrograms/kg, thiopentone 3-4 mg/kg and
      vecuronium 0.1 mg/kg and were ventilated with oxygen, nitrous oxide and
      isoflurane for 3 minutes prior to laryngeal mask insertion or tracheal
      intubation. Blood pressure and heart rate decreased equally in both groups after
      induction of anaesthesia. Haemodynamic variables increased after tracheal
      intubation but were unchanged after laryngeal mask insertion (P < 0.05 for
      intergroup differences). Heart rate, but not blood pressure, increased above
      baseline levels in the tracheal intubation group. The anaesthetic technique used
      blunted the haemodynamic response to tracheal intubation, but completely blocked
      the response to laryngeal mask insertion.

PMID- 9164153
TI  - Sequential oesophago-bronchoscopy.
AB  - Combined sequential oesophago-bronchoscopy with the same fibre-optic instrument
      is described, and complete safety of this procedure emphasised. It has the great
      advantage of reducing hospitalisation time for the patients, usually avoiding
      general anaesthesia, and considerably reducing costs, without prejudicing the
      patient's safety and interests.

PMID- 9164154
TI  - Use of the local leech Hirudo michaelseni in reconstructive plastic and hand
      surgery.

PMID- 9164156
TI  - The pattern of surgery in four hospitals in east and central Africa--implications
      for general surgical training.

PMID- 9164155
TI  - Perforation of the gastro-intestinal tract by a foreign body.

PMID- 9164157
TI  - Injection of ultrasmall samples and single molecules into tapered capillaries.
AB  - A novel injection scheme is described in which ultrasmall samples in the
      attoliter (10(-18) L) and low femtoliter (10(-15) L) range, or even single
      molecules, are controllably introduced into a tapered capillary so that
      electrophoretic separation can be carried out. To match the dimensions of the
      capillary inlet with that of the sample, capillary tips are tapered to an inside
      diameter ranging from hundreds of nanometers to a few micrometers. To inject an
      ultrasmall sample, optical trapping is used to immobilize and manipulate the
      sample in order to place it inside or next to the capillary inlet. A small
      controlled suction results in the loading of the sample into the capillary.

PMID- 9164158
TI  - On-line micellar electrokinetic chromatography-electrospray ionization mass
      spectrometry using anodically migrating micelles.
AB  - On-line micellar electrokinetic chromatography (MEKC)-electrospray ionization
      mass spectrometry (ESIMS) is demonstrated for the analysis of chlorotriazine
      herbicides and barbiturates. In this study, the micellar velocity is directly
      manipulated by the adjustment of electroosmosis rather than the electrophoretic
      velocity of the micelle. The electroosmotic flow is adjusted against the
      electrophoretic velocity of the micelle by changing the solution pH in MEKC. The
      elimination of MEKC surfactant introduction into ESIMS is achieved with an
      anodically migrating micelle, moving away from the electrospray interface. The
      effects of moving surfactant boundary in the MEKC capillary on separation
      efficiency and resolution of triazine herbicides and barbiturates are
      investigated. The mass detection of herbicides and barbiturates sequentially
      eluted from the MEKC capillary is acquired using the positive and negative
      electrospray modes, respectively.

PMID- 9164159
TI  - Characterization of vinyl-substituted, carbon-carbon double bonds by GC/FT-IR
      analysis.
AB  - Vapor-phase infrared spectra allow the determination of the stereochemistry of
      carbon-carbon double bonds conjugated with a vinyl group. Cis and trans isomers
      of unsubstituted 1,3-alkadienes can be differentiated on the basis of the
      differences observed in the 900-1000 cm-1 region (spectra of cis isomers show two
      bands at 993 and 906 cm-1, while those of trans compounds show three absorptions
      at 998, 949, and 902 cm-1) and the 1590-1650 cm-1 region (the C=C stretch bands
      are observed at 1595 and 1642 cm-1 for cis compounds and at 1604 and 1650 cm-1
      for trans compounds). Compounds bearing CH2=CHC(CH3)=CHCH2- and CH2=CHC(=CH2)-CH2
      structural moieties, referred to as alpha- and beta-type compounds, are
      frequently encountered as natural products. For compounds bearing alpha-type
      groups, the cis/trans configuration of the trisubstituted double bond can be
      determined unambiguously. An absorption at 3095-3091 cm-1, for the =CH2 stretch
      vibration, is common to both of these groups; however, due to the presence of two
      =CH2 groups, the relative intensity of the band is much higher for beta-type
      compounds. For alpha-type compounds, a cis configuration at the C-3 carbon atom
      is characterized by a =CH2 wag absorption at 907-906 cm-1. For beta-type
      compounds and 3E-alpha-type compounds, this band appears at 899-897 cm-1. In
      addition, a wavy "fingerprint" pattern with two minima at 1632 (low intensity)
      and 1595-1594 cm-1 (high intensity) is characteristic for beta-type compounds.
      Our generalizations are based on spectra of cis and trans ocimene, myrcene, and
      dehydration products of many 3-methyl-1-alken-3-ols. Six isomers of farnesene can
      be characterized by GC/FT-IR. Furthermore, gas-phase IR allows the determination
      of the configuration of the trisubstituted double bond at C-3 in alpha-type
      farnesene congeners. For example, the homo- and bishomofarnesene isomers from
      Myrmica ants were shown to include a 3Z bond.

PMID- 9164160
TI  - Identification, quantification, and relative concentrations of carotenoids and
      their metabolites in human milk and serum.
AB  - Thirty-four carotenoids, including 13 geometrical isomers and eight metabolites,
      in breast milk and serum of three lactating mothers have been separated,
      identified, quantified, and compared by high-performance liquid chromatography
      (HPLC)-photodiode array (PDA) detection-mass spectrometry (MS). Among the
      metabolites were two oxidation products of lycopene and four of lutein/
      zeaxanthin. In addition, two metabolites of lutein, formed as a result of
      dehydration of this dihydroxycarotenoid under acidic conditions similar to those
      of the stomach, have also been identified in plasma and breast milk. The
      oxidative metabolites of lycopene with a novel five-membered-ring end group have
      been identified as epimeric 2,6-cyclolycopene-1,5-diols by comparison of their
      HPLC-UV/visible-MS profiles with those of fully characterized (1H- and 13C-NMR
      spectroscopy) synthetic compounds. The HPLC procedures employed also detected
      vitamin A, two forms of vitamin E (gamma- and alpha-tocopherol), and two non
      carotenoid food components, i.e., piperine and caffeine, in serum and breast
      milk.

PMID- 9164161
TI  - Interlaboratory comparison of autoradiographic DNA profiling measurements. 4.
      Protocol effects.
AB  - The observed total interlaboratory uncertainty in restriction fragment length
      polymorphism (RFLP) measurements is sufficiently small to be of little
      significance given current forensic needs. However, as the number of RFLP data
      increase, further reduction in the total uncertainty could help minimize the
      resources required to evaluate potential profile matches. The large number of
      data available enable quantitative estimation of the within-laboratory
      imprecision and among-laboratory bias contributions to the total uncertainty.
      Some small but consistent among-laboratory measurement biases can be attributed
      to specific procedural or materials differences. The bias direction is often
      fragment-specific and thus unpredictable for unknown samples. Actions that would
      minimize currently recognized sources of interlaboratory bias include the
      following: (1) all laboratories should use the same algorithm for data
      interpolation, (2) all laboratories should use the same sizing ladders, (3) each
      laboratory should prepare control DNA and sample DNA in the same manner and with
      the identical reagents, (4) all laboratories should adopt a uniform policy on
      ethidium bromide use, and (5) all laboratories should adopt the same control DNA
      sizing acceptability criteria.

PMID- 9164162
TI  - Fluorescence lifetime measurement via a radionuclide-scintillation light source
      and analog cross correlation.
AB  - beta-Emitting 90Sr is used with a plastic scintillator to produce excitation
      light pulses for fluorescence lifetime analysis. This light source is less
      expensive, more compact, and much more reliable than traditionally employed
      excitation sources such as lasers or pulsed flash lamps. The pulse train from
      this light source varies randomly in amplitude and time. Cross-correlation signal
      analysis is ideal for such a source because, unlike other time domain techniques,
      cross correlation takes complete advantage of its random nature. Here we report
      on the construction of an instrument and the methods employed to make
      fluorescence lifetime measurements via the new source and an analog correlation
      processor. Although the light intensity of the scintillator-based excitation
      source is comparatively low, an adequate signal level can be generated. The
      fluorescence lifetimes of three fluorophores are measured with a 1-mCi
      radionuclide to demonstrate a lifetime range from less than 1.5 to 28 ns. Long
      lifetime measurements require an extra calibration step in order to compensate
      for delay cable energy loss. The light collection efficiency of the current
      instrument was found to be undesirably low; improvements in the instrument optics
      are suggested that will increase the collection efficiency and enhance the
      detection capability.

PMID- 9164163
TI  - High-performance liquid chromatography/electrospray mass spectrometry for the
      analysis of modified bases in DNA: 7-(2-hydroxyethyl)guanine, the major ethylene
      oxide-DNA adduct.
AB  - A method was developed for the analysis of 7-(2-hydroxyethyl)guanine (7HEG), the
      major DNA adduct formed after exposure to ethylene oxide (EO). The method is
      based on DNA neutral thermal hydrolysis, adduct micro-concentration, and final
      characterization and quantification by HPLC coupled to single-ion monitoring
      electrospray mass spectrometry (HPLC/SIR-ESMS). The method was found to be
      selective, sensitive, and easy to handle with no need for enzymatic digestion or
      previous sample derivatization. Detection limit was found to be close to 1 fmol
      of adduct injected (10(-10) M), thus allowing the detection of approximately
      three modified bases on 10(8) intact nucleotides in blood sample analysis.
      Quantification results are shown for 7HEG after calf thymus DNA and blood
      exposure to various doses of EO, in both cases obtaining clear dose-response
      relationships.

PMID- 9164164
TI  - Synthesis and biological activity of nifuroxazide and analogs.
AB  - Nifuroxazide and thirteen analogs were synthesized from substituted benzoic acids
      and minimal inhibitory concentrations were determined using the serial dilution
      tests, in three sequential steps. Nifuroxazide and chloramphenicol were used as
      reference standards. The tests were performed in TSB against the standard
      bacterial strain of Staphylococcus aureus ATCC 25923.

PMID- 9164165
TI  - Synthesis and cardiotonic activity of certain imidazo[2,1-b]-1,3,4-thiadiazole
      derivatives.
AB  - A series of 5-imino-2-methyl-4-(4'-substituted phenacyl)-1,3, 4-thiadiazole
      derivatives 3-5 have been synthesized and further used to prepare a series of 2
      methyl-6-(4'-substituted phenyl)imidazo[2, 1-b]-1,3,4-thiadiazoles 6-8 and 5
      substituted-2-methyl-6-(4'-substituted phenyl) imidazo[2, 1-b]-1,3, 4
      thiadiazoles 9-18. All of newly prepared imidazothiadiazole compounds were
      screened for their cardiotonic activity in isolated guinea pig atria. The
      detailed synthesis, spectroscopic and biological data are reported.

PMID- 9164167
TI  - Synthesis and evaluation of some new substituted benzofuran derivatives as
      potentially active antimicrobial agents.
AB  - 6-(omega-Bromoacetyl)-2,3-diphenyl-5-methoxybenzofuran derivative (2) was
      synthesized and allowed to react with different reagents to get new benzofuran
      derivatives that are substituted with isolated or fused heterocyclic ring
      systems. The antimicrobial activity of the hitherto synthesized products was
      tested and evaluated.

PMID- 9164166
TI  - A new bioactive metabolite from Xanthoria steineri .
AB  - The ether extract of the lichen Xanthoria steneri Lamb yielded two new octanoic
      acid derivatives identified as 3-hydroxy 2,4, 6-trimethyl octanoic acid (xantoric
      acid A) and 3-O-[3'-hydroxy-2',4',6'-trimethyl octanoate]-2,4,6 trimethyl
      octanoic acid (xanthoric acid B). In addition, 3-methyl orsellinic acid methyl
      ester (2, 4-dihydroxy-3,6-dimethyl benzoic acid methyl ester), physcion and 5
      alpha-stigmast-7-en-3 beta-OI were further isolated and identified on the basis
      of spectral data. The biological profile of xanthoric acid B revealed a wide
      range of bioactivity including cytotoxicity, anticonvulsant, antibacterial and
      antimycotic properties.

PMID- 9164168
TI  - Synthesis and biological activity studies of 1,3,4-thiadiazolo[2,3-c]-as
      triazines.
AB  - Several new 1,3,4-thiadiazolo[2,3-c]-as-triazines were synthesized by the
      reaction of 6-substituted-4-amino-3-mercapto-1,3,4-triazon-5 (4H)-ones with
      appropriate aromatic and heterocyclic carboxylic acids in the presence of
      phosphorus oxychloride. The structures of the newly synthesized compounds were
      established on the basis of analytical, IR, NMR and mass spectral data. Some
      selected compounds from this series were subjected to both antimicrobial and
      pharmacological studies.

PMID- 9164169
TI  - HPLC determination of ITF 188 and its metabolite ITF 1078 in urine after
      intranasal administration of new heparin salt ITF 1300 to dogs.
AB  - Heparin salt ITF 1300 in which low molecular weight heparin is salified with a
      new counterion, di-[3-(N,N-dibutylamino)]propyl carbonate (ITF 188), was selected
      for the pharmacological development. A specific, sensitive and reproducible HPLC
      method for the determination of ITF 188 and its alcoholic metabolite ITF 1078 in
      urine was developed. The method was employed for the study of urinary excretion
      of the counterion after intranasal administration of ITF 1300 to dogs. The total
      amount of ITF 188 and ITF 1078 found in urine within 72 hours after the nasal
      instillation of ITF 1300 accounts for about 5% of the administered dose.

PMID- 9164170
TI  - Factors affecting the spread of double-stranded RNA viruses in Aspergillus
      nidulans.
AB  - Viruses are common in asexual Aspergilli but not in sexual Aspergilli. We found
      no viruses in 112 isolates of the sexual Aspergillus nidulans. We have
      investigated factors that could play a role in preventing the spread of
      mycoviruses through populations of A. nidulans. Experiments were performed with
      A. nidulans strains infected with viruses originating from A. niger. Horizontal
      virus transmission was restricted but not prevented by somatic incompatibility.
      Viruses were transmitted vertically via conidiospores but not via ascospores.
      Competition experiments revealed no effect of virus infection on host fitness.
      Outcrossing was found to limit the spread of viruses significantly more than
      selfing. It is concluded that the exclusion of viruses from sexual Aspergilli
      could be due to the formation of new somatic incompatibility groups by sexual
      recombination.

PMID- 9164172
TI  - Evolution of a lesser fitness trait: egg production in the specialist Drosophila
      sechellia.
AB  - In the evolutionary process during which Drosophila sechellia became specialized
      on a toxic fruit (morinda), a spectacular decrease in female reproductive
      capacity took place when compared with the species' generalist relatives D.
      mauritiana and D. simulans. Comparisons of species and interspecific crosses
      showed that two different traits were modified: number of ovarioles and rate of
      egg production. During the conservation of a D. sechellia strain on usual food,
      adaptation to laboratory conditions led to an increase in the rate of oogenesis
      but not in ovariole number. Comparison of F1 and backcross progeny also suggests
      that the two traits are determined by different genes (ovariole number has
      already been shown to be polygenic). When morinda is available as a resource, the
      low rate of egg production in D. sechellia is partly compensated by a stimulating
      effect, while an inhibition occurs in D. simulans. It is assumed that D.
      sechellia progressively adapted itself from rotten, non-toxic morinda to a
      fresher and more toxic resource. During this process the rate of oogenesis
      evolved from an inhibition to a stimulation by morinda. Simultaneously a
      spectacular decrease in ovariole number took place, either as a consequence of
      stochastic events related to the small population size of D. sechellia and a
      metapopulation dynamics, or as an adaptive process favouring dispersal capacities
      of the female.

PMID- 9164171
TI  - Mutational analysis of the rolA gene of Agrobacterium rhizogenes in tobacco:
      function of the rolA pre-mRNA intron and rolA proteins defective in their
      biological activity.
AB  - The rolA gene of Agrobacterium rhizogenes contains in its untranslated leader
      region a spliceosomal intron, which is spliced in Arabidopsis and in Nicotiana
      tabacum. Expression under the control of the 35S promoter from cauliflower mosaic
      virus of a rolA gene derivative defective in splicing still causes alterations of
      growth in transgenic tobacco plants. Splicing of rolA mRNA is required for
      efficient expression of the rolA phenotype in vivo. Moreover, splicing is
      required for efficient in vitro translation of the rolA mRNA. In contrast,
      expression of a 35S-rolA gene derivative with the ATG initiation codon replaced
      by ATA does not cause any phenotypical alteration. Mutations leading to amino
      acid substitutions at positions 37 and 40 of the rolA coding region were isolated
      as null mutants in Arabidopsis plants transgenic for the rolA gene. However, when
      expressed in tobacco under the control of the 35S promoter, they cause a rolA
      phenotype reduced in the expressivity of its traits. The molecular
      characterization of rolA mutants might be useful for understanding the
      biochemical function of the rolA protein.

PMID- 9164173
TI  - Conservation genetics of the koala (Phascolarctos cinereus): low mitochondrial
      DNA variation amongst southern Australian populations.
AB  - Koala (Phascolarctos cinereus) populations in southern Australia have a history
      of bottlenecks-earlier this century the species became extinct in South
      Australia, and almost so in Victoria. Subsequently large numbers of animals from
      island populations (founded from very few animals) have been translocated back to
      mainland sites and to other islands in the region. As part of a larger study of
      the genetic structure of koala populations in southern Australia, we have
      undertaken a survey of mitochondrial DNA restriction fragment length polymorphism
      (mtDNA-RFLP) variability. Genomic DNA from 91 koalas from five populations was
      examined using 23 restriction enzymes, and mtDNA fragments were detected using a
      domestic cat full-length mtDNA clone. Only one of the enzymes, TaqI, revealed
      polymorphism-a relatively low amount of variation compared with other mammals,
      although low mtDNA-RFLP variation has also been reported in Queensland koalas.
      French Island and populations established predominantly from French Island
      immigrant koalas, either directly or via other island populations, were
      indistinguishable by haplotype frequencies. The mtDNA data are thus consistent
      with the interpretation that the koala translocation programme has homogenized
      gene frequencies amongst those populations involved. South Gippsland is not
      recorded as having received translocated koalas directly, and has significantly
      different mtDNA-RFLP haplotype frequencies from all other populations examined.
      The fact that this distinction was not previously observed in nuclear gene
      frequencies may reflect predominantly male-mediated dispersal in koalas.

PMID- 9164174
TI  - Using the variance of pairwise differences to estimate the recombination rate.
AB  - A new estimator is proposed for the parameter C = 4Nc, where N is the population
      size and c is the recombination rate in a finite population model without
      selection. The estimator is an improved version of Hudson's (1987) estimator,
      which takes advantage of some recent theoretical developments. The improvement is
      slight, but the smaller bias and standard error of the new estimator support its
      use. The variance of the average number of pairwise differences is also derived,
      and is important in the formulation of the new estimator.

PMID- 9164175
TI  - Joint regulation of cell size and cell number in the wing blade of Drosophila
      melanogaster.
AB  - We used Drosophila melanogaster to test for compensatory control of cell area and
      cell number in the regulation of total wing area. In two random bred wild-type
      base stocks collected from different geographic locations we found a negative
      association between the area and the number of cells in the wing blade. Three
      replicate lines were selected for increased or decreased wing area, with cell
      area maintained at the same level as in the three controls. After eight
      generations of selection, despite a large and highly significant difference in
      wing area between the large, control and small selection lines, cell area did not
      differ significantly between them. Rather, the difference in wing area between
      selection regimes was attributable to differences in cell number. Over the course
      of selection, the initially significant negative correlation between cell area
      and cell number in the wing increased, providing evidence for compensatory
      regulation of cell area and cell number. As a result of the increasingly negative
      association between the two traits, the variance in wing area declined as
      selection proceeded. It will be important to discover the mechanisms underlying
      the compensatory regulation of cell area and cell number.

PMID- 9164176
TI  - CHOP may have been part of the beginning but certainly not the end: issues in
      risk-related therapy of large-cell lymphoma.

PMID- 9164177
TI  - Bleomycin in germ cell tumor therapy: not all regimens are created equal.

PMID- 9164178
TI  - Intensive sequential chemotherapy with repeated blood stem-cell support for
      untreated poor-prognosis non-Hodgkin's lymphoma.
AB  - PURPOSE: To demonstrate the feasibility and efficacy of six ambulatory high-dose
      sequential chemotherapy courses that include three intensified cycles supported
      by stem-cell infusion in high-risk and high-intermediate-risk untreated non
      Hodgkin's lymphoma (NHL) patients. PATIENTS AND METHODS: A pilot nonrandomized
      study included 20 untreated patients aged less than 60 years with aggressive
      histologically identified NHL and two or three adverse-prognosis criteria
      (International Index). Patients received an ambulatory regimen with high-dose
      chemotherapy supported by granulocyte colony-stimulating factor (G-CSF) and
      repeated peripheral-blood stem-cell (PBSC) infusion. The median age was 39 years
      (range, 20 to 59), with 13 men and seven women. Chemotherapy consisted of one
      cycle every 21 days for a total of six cycles. The first three cycles (A1, A2,
      and A3) consisted of cyclophosphamide (Cy) 3,000 mg/m2, doxorubicin (Doxo) 75
      mg/m2, and vincristine 2 mg (plus corticosteroids). The last three cycles (B4,
      B5, and B6) consisted of the same drug combination plus etoposide 300 mg/m2 and
      cisplatin 100 mg/m2. For an expected duration of 18 weeks, the projected dose
      intensity was 25 mg/m2/wk for Doxo and 1,000 mg/m2/wk for Cy. G-CSF 300
      micrograms was administered from day 6 following each cycle until neutrophil
      reconstitution. Two aphereses were performed at approximately day 13 after each A
      cycle, and PBSCs were injected at day 4 of each B cycle. Radiotherapy on tumor
      masses > or = 5 cm was scheduled after completion of the last cycle. RESULTS: The
      median duration of grade 4 neutropenia was 1 day (range, 0 to 7) for each A cycle
      and 4 days (range, 1 to 10) for each B cycle (P = .02). The median duration of
      grade 4 thrombopenia was 0 days (range, 0 to 8) for each A cycle and 6 days
      (range, 1 to 21) for each B cycle (P < .001). Hospitalization for febrile
      neutropenia was required for 18% and 44% of patients during cycles A and B,
      respectively (P < .01). Only three patients did not complete the protocol: one
      due to emergency surgery after cycle B4, one who died after cycle B5 from
      interstitial pneumonia, and one with delayed hematologic reconstitution after
      cycle B4. Chemotherapy delivery was optimal (median actual relative dose
      intensity, 97%; range, 66 to 100). The median total dose administered over 18
      weeks was 18,000 mg Cy (range, 12,000 to 18,000), 450 mg Doxo (range, 300 to
      450), 900 mg etoposide (range, 300 to 900), and 300 mg cisplatin (range, 100 to
      300). Evaluation of response after six courses showed 13 complete remissions
      ([CRs] 65%), four partial remissions (PRs), two nonresponses (NRs), and one toxic
      death. With a median follow-up period of 25 months (range, 16 to 43), 15 patients
      are alive, with 12 in continuous first CR; five patients relapsed (four of four
      PRs and one of 13 CRs). Two-year survival and failure-free survival (FFS) rates
      are 73% and 56%, respectively. The disease-free survival (DFS) rate for the CRs
      is 86%. CONCLUSION: PBSC support contributes to the feasibility of first-line,
      very-high-dose, ambulatory chemotherapy delivery in poor-risk NHL and is
      associated with a high rate of remission and FFS.

PMID- 9164179
TI  - Randomized trial showing equivalent efficacy of filgrastim 5 micrograms/kg/d and
      10 micrograms/kg/d following high-dose chemotherapy and autologous bone marrow
      transplantation in high-risk lymphomas.
AB  - PURPOSE: To evaluate the effect of two filgrastim dosages after autologous bone
      marrow transplantation (ABMT) in patients with Hodgkin's disease (HD) and non
      Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Eighty-six patients were enrolled
      onto a multicenter, randomized, open-label study. The study compared the efficacy
      and safety of two different doses of filgrastim, 5-microgram/kg/d subcutaneous
      (SC) bolus injection and 10-microgram/kg/d SC continuous infusion, starting on
      day 1 following ABMT. RESULTS: Both patient groups were well matched in terms of
      demography and disease. The results showed no statistical difference in the
      median time to reach an absolute neutrophil count (ANC) of 0.5 x 10(9)/L (11
      days; P = .685) and no difference in the median duration of neutropenia (10 v 11
      days, respectively; P = .567) between either dose of filgrastim. The incidence
      and duration of fever and neutropenic fever were the same in both groups. The
      number and mean duration of clinically and documented infections, duration of
      intravenous (IV) antibiotics, time to discharge from hospital, and tumor response
      also were similar in both groups. CONCLUSION: This study demonstrates that a dose
      of filgrastim 5 micrograms/kg/d administered as a daily SC bolus injection has a
      similar efficacy and safety profile compared with the 10-microgram/kg/d dose
      administered as a SC continuous infusion. The lower dose of filgrastim has
      potential cost-saving implications in terms of both the dose of drug administered
      and the ease of administration. Based on these findings, the recommended dose of
      filgrastim after ABMT should be 5 micrograms/kg/d.

PMID- 9164180
TI  - Stanford-Kaiser Permanente G1 study for clinical stage I to IIA Hodgkin's
      disease: subtotal lymphoid irradiation versus vinblastine, methotrexate, and
      bleomycin chemotherapy and regional irradiation.
AB  - PURPOSE: We have demonstrated that a relatively mild chemotherapy regimen,
      vinblastine, methotrexate, and bleomycin (VBM), and involved-field radiotherapy
      (IFRT) could substitute for extended-field radiotherapy in patients with
      favorable Hodgkin's disease (HD) who have been laparotomy-staged. The purpose of
      this study is to determine if VBM and regional radiotherapy can substitute for
      extended-field radiotherapy in favorable clinical stage (CS) I and II HD.
      PATIENTS AND METHODS: Seventy-eight patients with favorable CS I to II HD were
      randomly assigned to subtotal lymphoid irradiation (STLI) or VBM chemotherapy and
      regional radiotherapy. Randomization was stratified on the basis of age, sex,
      number of Ann Arbor sites, histology, and institution. Patients were evaluated
      for freedom from progressive HD, survival, and toxicity. Results were compared
      with the predecessor trial in pathologically staged patients. RESULTS: With a
      median follow-up period of 4 years, the rate of freedom from progressive HD was
      92% (95% confidence interval [CI], 88% to 96%) for patients treated with STLI and
      87% (95% CI, 81% to 93%) for patients treated with VBM and regional radiotherapy.
      Six of seven patients who relapsed are alive and in remission following
      successful second-line therapy. CONCLUSION: Given the caveat of a small number of
      patients, the results of extended-field radiotherapy and VBM and regional
      radiotherapy are comparable with a median follow-up period of 4 years. VBM serves
      as a paradigm to reduce late effects in favorable early-stage HD. We do not
      advocate its routine use in clinical practice, but instead encourage
      participation in clinical trials with the objective of maintaining efficacy while
      reducing toxicity in CS I and II HD.

PMID- 9164181
TI  - Late relapse in patients with diffuse large-cell lymphoma treated with MACOP-B.
AB  - PURPOSE: To examine the clinical course of patients who experienced a late
      relapse after initial curative chemotherapy for advanced-stage diffuse large-cell
      lymphoma. PATIENTS AND METHODS: Between April 1981 and June 1986, 127 patients
      with de novo advanced-stage diffuse large-cell lymphoma were treated with a 12
      week chemotherapy program (methotrexate, doxorubicin, cyclophosphamide,
      vincristine, prednisone, and bleomycin [MACOP-B]). The overall survival rate at
      10 years is 52%. One hundred six patients (83%) entered a complete remission (CR)
      and 43 of them relapsed. With a median follow-up duration of 146 months, 26
      patients relapsed early and 17 relapsed late, ie, after a continuous CR (cCR) of
      greater than 24 months. All late relapses occurred in patients with B-cell
      lymphoma. RESULTS: After 24 months from diagnosis, the rate of late relapse
      averaged 2.2% per year and reached a projected 22% actuarial risk of late relapse
      after 10 years. The median time to late relapse was 69 months (range, 38 to 141).
      Ten patients relapsed with aggressive histologic subtypes and were treated with
      curative intent using anthracycline-based chemotherapy. Four remain in second CR,
      one is alive with disease, and five died of disease or while on treatment. The 6
      year overall survival rate from the time of relapse (SFR) for these 10 patients
      is 42%. Six patients relapsed with low-grade follicular lymphoma. These patients
      received various treatments intended to control, but not necessarily cure
      disease. One is in second CR, one is alive with disease, and four died of disease
      or while on treatment. The 6-year overall SFR rate for these six patients is 40%.
      bcl-2 translocation and Bcl-2 protein expression at diagnosis did not predict for
      the type of late relapse. One patient did not undergo repeat biopsy at relapse
      and died 9 months later despite aggressive therapy. CONCLUSION: Curative therapy
      should be attempted in patients who relapse late with aggressive-histology
      lymphoma and those who relapse with follicular histology may benefit from
      palliative treatment. The behavior of late-relapse lymphoma is similar to de novo
      lymphoma, with outcome dictated by the histologic subtype at relapse.

PMID- 9164182
TI  - Comparative diagnostic accuracy of magnetic resonance imaging and
      immunoscintigraphy for detection of bone marrow involvement in patients with
      malignant lymphoma.
AB  - PURPOSE: To compare the diagnostic accuracy of magnetic resonance imaging (MRI)
      and immunoscintigraphy (IS) for detection of bone marrow infiltration in
      malignant lymphoma. PATIENTS AND METHODS: In 32 patients with Hodgkin's disease
      (HD) or non-Hodgkin's lymphoma (NHL), MRI of the axial skeleton and whole-body IS
      using technetium-99m (99mTc)-labeled monoclonal antibodies were reviewed and
      compared with iliac crest biopsies. Criterion for marrow infiltration was a
      positive biopsy or concordant positive results of MRI and IS. RESULTS: In 16
      patients (50%), MRI, IS, and iliac crest biopsies were negative for marrow
      infiltration. Iliac crest biopsy showed infiltration in only four patients (13%).
      Infiltration was missed in two of 32 patients with IS and in one patient with
      MRI. In one additional patient, MRI was false-positive because of pelvic
      hematopoietic hyperplasia. A subset of nine patients (28%) with negative biopsies
      had bone marrow involvement according to MRI and IS with identical location and
      pattern of infiltration. In eight of these nine patients, diagnostic imaging
      indicated marrow involvement only in noncrest marrow. Subsequent biopsy confirmed
      infiltration in five patients. The clinical course suggested true-positive
      imaging results in the remaining four patients. Two patients (6%) remained
      equivocal. Overall concordance of MRI and IS for marrow infiltration was 88% (28
      of 32 patients). CONCLUSION: Diagnostic imaging is essential for optimal staging
      in malignant lymphoma, as blind biopsies appear to have low sensitivity for bone
      marrow infiltration because of frequent involvement in noncrest marrow. both
      imaging modalities show a high rate of detection of bone marrow infiltration.

PMID- 9164183
TI  - Endoscopic ultrasound in the evaluation of gastric small lymphocytic mucosa
      associated lymphoid tumors.
AB  - PURPOSE: Low-grade, small lymphocytic lymphomas of the mucosa-associated lymphoid
      tissue (MALT) have recently been shown to be associated with Helicobacter pylori
      infections. Regression of these tumors has been reported with antibiotic therapy.
      Here we evaluate endoscopic ultrasound (EUS) as on objective method to evaluate
      pretreatment disease and posttherapy response. MATERIALS AND METHODS: We
      retrospectively reviewed 20 patients initially diagnosed elsewhere with MALT
      lymphoma. All patients had their initial endoscopic biopsies (EGDs) reviewed at
      Memorial Sloan-Kettering Cancer Center (MSKCC). All patients had EUS performed at
      the time of consultation and on completion of therapy if treated at our center.
      Antral biopsies were stained with a modified Steiner preparation to determine
      infection by H pylori. RESULTS: Gastric low-grade lymphoma was confirmed in 16 of
      20 patients; 11 of 16 had previously received antibiotic therapy for biopsy
      positive H pylori infection. All gastric lymphomas had an abnormal EUS: eight
      with discrete tumor masses and eight with gastric wall infiltration (submucosa, n
      = 4; muscularis propria, n = 3; serosa, n = 1). On completion of lymphoma
      treatment with chemotherapy, radiotherapy, or surgery, 11 of 16 patients
      underwent follow-up EUS. Five patients received care elsewhere and did not return
      for posttreatment EUS. The gastric wall was normal with no evidence of disease on
      EUS-guided biopsy in eight of 11 patients. The remaining three patients had
      abnormal gastric walls. One was biopsy-negative and two had residual lymphoma.
      Four patients were found to have benign lymphoid aggregates in association with H
      pylori on initial EGD and EUS biopsies. All four patients were previously
      untreated with antibiotics. EUS showed prominent mucosa, but no significant
      findings within the gastric wall. CONCLUSION: EUS appears useful to stage
      objectively and evaluate therapeutic outcome in the management of gastric, low
      grade MALT lymphomas. It also helps to distinguish benign lymphoid aggregates
      from lymphoma associated with H pylori infection. EUS findings may have a
      significant impact on assessment and therapeutic recommendations.

PMID- 9164184
TI  - Results of allogeneic bone marrow transplants for leukemia using donors other
      than HLA-identical siblings.
AB  - PURPOSE: To compare outcomes of bone marrow transplants for leukemia from HLA
      identical siblings, haploidentical HLA-mismatched relatives, and HLA-matched and
      mismatched unrelated donors. PATIENTS: A total of 2,055 recipients of allogeneic
      bone marrow transplants for chronic myelogenous leukemia (CML), acute myelogenous
      leukemia (AML), and acute lymphoblastic leukemia (ALL) were entered onto the
      study. Transplants were performed between 1985 and 1991 and reported to the
      International Bone Marrow Transplant Registry (IBMTR). Donors were HLA-identical
      siblings (n = 1,224); haploidentical relatives mismatched for one (n = 238) or
      two (n = 102) HLA-A, -B, or -DR antigens; or unrelated persons who were HLA
      matched (n = 383) or mismatched for one HLA-A, -B, or -DR antigen (n = 108). HLA
      typing was performed using serologic techniques. RESULTS: Transplant-related
      mortality was significantly higher after alternative donor transplants than after
      HLA-identical sibling transplants. Among patients with early leukemia (CML in
      chronic phase or acute leukemia in first remission), 3-year transplant-related
      mortality (+/-SE) was 21% +/- 2% after HLA-identical sibling transplants and
      greater than 50% after all types of alternative donor transplants studied. Among
      patients with early leukemia, relative risks of treatment failure (inverse of
      leukemia-free survival), using HLA-identical sibling transplants as the reference
      group, were 2.43 (P < .0001) with 1-HLA-antigen-mismatched related donors, 3.79
      (P < .0001) with 2-HLA-antigen-mismatched related donors, 2.11 (P < .0001) with
      HLA-matched unrelated donors, and 3.33 (P < .0001) with 1-HLA-antigen-mismatched
      unrelated donors. For patients with more advanced leukemia, differences in
      treatment failure were less striking: 1-HLA-antigen-mismatched relatives, 1.22 (P
      = not significant [NS]); 2-HLA-antigen-mismatched relatives, 1.81 (P < .0001);
      HLA-matched unrelated donors, 1.39 (P = .002); and 1-HLA-antigen-mismatched
      unrelated donors, 1.63 (P = .002). CONCLUSION: Although transplants from
      alternative donors are effective in some patients with leukemia, treatment
      failure is higher than after HLA-identical sibling transplants. Outcome depends
      on leukemia state, donor-recipient relationship, and degree of HLA matching. In
      early leukemia, alternative donor transplants have a more than twofold increased
      risk of treatment failure compared with HLA-identical sibling transplants. This
      difference is less in advanced leukemia.

PMID- 9164185
TI  - Deletions of p15 and/or p16 genes as a poor-prognosis factor in adult T-cell
      leukemia.
AB  - PURPOSE: To determine the frequency of the deletions of p15/p16 genes in adult T
      cell leukemia (ATL) cells and to evaluate their value in the diagnosis of
      clinical subtypes of ATL patients and the prediction of their clinical outcome.
      MATERIALS AND METHODS: Peripheral-blood samples from 114 patients with ATL were
      examined by Southern blot analysis. In five chronic-type patients who showed
      disease progression to acute type, serial samples also were examined. RESULTS:
      Among 114 patients, 28 (24.6%) showed the deletions of p15 and/or p16 genes. The
      results were well correlated with the clinical subtypes. Patients with deleted
      p15 and/or p16 genes had significantly shorter survival times than the patients
      in whom both genes were preserved (P < .0001). A similar decline in survival time
      was observed in the analyses within the same subtypes. In multivariate analysis
      using the Cox proportional hazard model, the deletions of p15 and/or p16 genes
      emerged as an independent prognostic indicator. Moreover, three of the five
      chronic-type patients who progressed to acute type lost the p16 gene alone or
      both the p15 and p16 genes at their exacerbation phase. CONCLUSION: The results
      suggest the following: (1) that the deletions of p15 and/or p16 genes play a key
      role in the progression of ATL; and (2) that these deletions are reliable
      prognostic factors that predict shortened survival times.

PMID- 9164186
TI  - Secondary cytogenetic changes in acute promyelocytic leukemia--prognostic
      importance in patients treated with chemotherapy alone and association with the
      intron 3 breakpoint of the PML gene: a Cancer and Leukemia Group B study.
AB  - PURPOSE: To examine, in newly diagnosed patients with acute promyelocytic
      leukemia (APL), the prognostic significance of secondary cytogenetic changes and
      the relationship between such changes and the two major promyelocytic leukemia
      retinoic acid receptor alpha (PML-RAR alpha) mRNA types. PATIENTS AND METHODS:
      One hundred sixty-one patients with t(15;17)(q22;q11-12) enrolled onto Cancer and
      Leukemia Group B (CALGB) protocol 8461, a prospective study of cytogenetics in
      acute myeloid leukemia (AML), were studied. Eighty of these 161 patients were
      treated solely with chemotherapy and evaluated for response to treatment and
      survival. PML-RAR alpha mRNA type was determined using reverse transcriptase
      polymerase chain reaction (RT-PCR) in 56 patients. RESULTS: The incidence of
      secondary cytogenetic abnormalities was 32%. Among 80 patients treated with
      chemotherapy, the presence of a secondary chromosome abnormality was associated
      with longer complete remission (CR) duration (median, 29.9 v 15.7 months; P =
      .03) and longer event-free survival (EFS) duration (median, 17.0 v 12.2 months; P
      = .03). There was no difference in overall survival (P = .28). In a separate
      group of 56 patients with both cytogenetic and molecular data, 32 had the type L
      PML-RAR alpha transcript (intron 6 PML breakpoint). Of these 32 patients, four
      (12.5%) had chromosome changes in addition to t(15;17), whereas 12 of 20 patients
      (60%) with the type 5 PML-RAR alpha transcript (intron 3 PML breakpoint) had
      secondary cytogenetic changes (P < .001). CONCLUSION: (1) Secondary cytogenetic
      changes do not confer a poor prognosis in APL patients treated with
      anthracycline/cytarabine (Ara-C)-based chemotherapy; and (2) A highly significant
      relationship exists between the PML-RAR alpha 5 isoform (intron 3 PML genomic
      breakpoint) and secondary cytogenetic changes in APL.

PMID- 9164187
TI  - Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC
      833 in relapsed or refractory acute myelogenous leukemia.
AB  - PURPOSE: Expression of the multidrug resistance gene (MDR1) p170 protein is
      frequent in leukemic blasts from patients with relapsed acute myelogenous
      leukemia (AML). A phase I study using the nonimmunosuppressive MDR1 blocker SDZ
      PSC-833 (PSC) in combination with mitoxantrone (MITO) and etoposide (VP) was
      performed. PATIENTS AND METHODS: Starting doses (LVL0) of MITO (3.25 mg/m2/d on
      days 1 and 3 to 6) and VP (210 mg/m2/d on days 1 and 3 to 5) were 40% of the
      maximal-tolerated dose (MTD) from a prior study. A 1.5-mg/kg loading dose of PSC
      was followed by a 120-hour continuous infusion of 10 mg/kg/d on days 2 to 6.
      Blood samples for PSC, MITO, and VP pharmacokinetics (PK) were taken on days 1
      and 3, and samples for MDR1 expression were taken on day 0. RESULTS: Severe
      mucositis developed in all patients at LVL0; therefore, MITO and VP doses were
      reduced to 2.5 and 170 mg/m2 (LVL-1) for the next seven patients, and this dose
      proved to be MTD. All LVL0 and three LVL-1 patients had transient elevations in
      the serum bilirubin level to > or = 4 mg/dL. Serum creatinine level increased to
      greater than 2 mg/dL in one case. There were no other grade 3 or 4 nonhematologic
      toxicities observed. The peripheral blood was cleared of leukemia in three LVL0
      and four LVL-1 patients. The marrow was cleared of leukemic cells in one LVL0 and
      five LVL-1 patients, and a significant reduction in marrow leukemic infiltrate
      was observed in eight of 10. No patient achieved complete remission (CR), and all
      died of progressive disease (n = 8) or infection (n = 2). MDR1 expression was
      detected by fluorescent-activated cell sorter (FACS) analysis in five of seven
      cases. An elevated MDR1 mRNA level was detected by quantitative polymerase chain
      reaction (Q-PCR) in six of eight cases studied. Clearing of leukemia cells from
      the marrow occurred in four of six MDR1-positive and one of three MDR1-negative
      patients. Despite the fact that LVL0 doses had to be reduced due to toxicity,
      coadministration of PSC did not produce a consistent effect on MITO PK; however,
      it did repeatedly lead to increased levels of VP in the serum. CONCLUSION: We
      conclude that PSC-MITO-VP is a tolerable regimen with antileukemic activity.
      Addition of PSC necessitated a 66% reduction in MITO and VP doses from a prior
      study without PSC.

PMID- 9164188
TI  - Second cancer risk in hairy cell leukemia: analysis of 350 patients.
AB  - PURPOSE: The discovery of effective therapy for hairy cell leukemia (HCL) has
      increased the relevance of long-term outcome. We have therefore examined the
      incidence of second cancers. PATIENTS AND METHODS: Data on 350 HCL patients was
      obtained from the M.D. Anderson Cancer Center Cancer Registry's computerized data
      base and from chart review. Standardized incidence ratios (SIRs) and standardized
      mortality ratios (SMRs) (observed/expected [O/E]) were calculated with the
      expected number determined using age, sex, and calendar-year-specific rates from
      the Connecticut Tumor Registry and from national mortality data, respectively.
      RESULTS: The median age of the patients was 50 years and the median follow-up
      duration was 6 years. Twenty-six patients developed a second cancer at least 6
      months after the HCL diagnosis (O/E ratio, 1.34; P = .08). There was no excess of
      malignancy among patients treated with interferon alfa (IFN-alpha; P = .27), 2
      chlorodeoxyadenosine (2CDA; P = .37), or deoxycoformycin (DCF; P = .7). However,
      an excess of myeloma-related neoplasms (O/E, 13.04; P < .001) and lymphomas (O/E,
      8.7; P = .03) was observed. Survival from the advent of systemic therapy for HCL
      was better than before this time (P = .0009). Nevertheless, mortality remained
      excessive (O/E, 6.17; P < .001), mainly because of HCL-related infections and
      secondary malignancy. CONCLUSION: Among 350 patients with HCL, there was an
      increase in the number of second cancers; however, it did not reach statistical
      significance and was not associated with therapy. The incidence of lymphoid
      neoplasms was significantly higher than expected. Survival since the advent of
      effective systemic therapy was excellent, although excess mortality was still
      observed.

PMID- 9164189
TI  - Asymptomatic recurrence detection with surveillance scanning in children with
      medulloblastoma.
AB  - PURPOSE: To assess the utility of surveillance neuroimaging in detecting
      recurrent disease in patients treated for medulloblastoma. PATIENTS AND METHODS:
      Records and scans of 59 consecutive patients treated for medulloblastoma between
      1984 and 1993 in one institution were retrospectively reviewed. RESULTS: Nineteen
      of 59 patients had recurrence of tumor, of which 17 were available for this
      study. Eleven of the 17 recurrent patients were asymptomatic at the time of
      detection. The median time to recurrence was 13 months (range, 3 to 90).
      CONCLUSION: Surveillance scanning detected a majority of recurrences before onset
      of symptoms. Although the outcome of those with recurrent disease remains poor,
      early detection with minimum disease provides the best setting in which to test
      newer therapies. Patients and their parents also were more likely to elect
      pursuing further treatment when relapse was detected asymptomatically.

PMID- 9164190
TI  - High-dose chemotherapy with autologous stem-cell rescue in patients with
      recurrent and high-risk pediatric brain tumors.
AB  - PURPOSE: We treated 49 patients with recurrent or poor-prognosis CNS malignancies
      with high-dose chemotherapy regimens followed by autologous marrow rescue with or
      without peripheral-blood stem-cell augmentation to determine the toxicity of and
      event-free survival after these regimens. PATIENTS AND METHODS: Nineteen patients
      had medulloblastomas, 12 had glial tumors, seven had pineoblastomas, five had
      ependymomas, three had primitive neuroectodermal tumors, two had germ cell
      tumors, and one had fibrosarcoma. Thirty-seven received chemotherapy with
      cyclophosphamide 1.5 g/m2 daily x 4 and melphalan 25 to 60 mg/m2 daily x 3. Nine
      received busulfan 37.5 mg/m2 every 6 hours x 16 and melphalan 180 mg/m2 (n = 7)
      or 140 mg/m2 (n = 2). Three received carboplatin 700 mg/m2/d on days -7, -5, and 
      3 and etoposide 500 mg/m2/d on days -6, -4, and -2. All patients received
      standard supportive care. RESULTS: Eighteen of 49 patients survive event-free 22+
      to 55+ months (median, 33+) after transplantation, including nine of 16 treated
      before recurrence and nine of 33 treated after recurrence. There was one
      transplant-related death from pulmonary aspergillosis. Of five patients
      assessable for disease response, one had a partial remission (2 months), one has
      had stable disease (55+ months), and three showed progression 2, 5, and 8 months
      after transplantation. CONCLUSION: The toxicity of these regimens was tolerable.
      Certain patients with high-risk CNS malignancies may benefit from such a
      treatment approach. Subsequent trials should attempt to determine which patients
      are most likely to benefit from high-dose chemotherapy with autologous stem-cell
      rescue.

PMID- 9164191
TI  - Systemic effect of intrathecal methotrexate during the initial phase of treatment
      of childhood acute lymphoblastic leukemia. The European Organization for Research
      and Treatment of Cancer Children's Leukemia Cooperative Group.
AB  - PURPOSE: The in vivo response to prephase corticosteroid therapy for 1 week has
      been described as a major prognostic factor in childhood acute lymphoblastic
      leukemia (ALL). Patients with less than 1,000 blasts/microL at day 8 are
      considered responders and have a better prognosis. This prephase therapy is
      usually considered as an evaluation of glucocorticoid sensitivity. In fact, it
      also includes one intrathecal (IT) injection of methotrexate (MTX). In this
      study, we try to clarify the influence of this injection of IT MTX on the
      response to the prephase therapy. PATIENTS AND METHODS: This retrospective study
      analyzed the response to prephase therapy in 1,044 children with ALL entered onto
      the European Organization for Research and Treatment of Cancer (EORTC) trial
      58881 of the Children's Leukemia Cooperative Group (CLCG). Analysis was
      restricted to 732 cases with an initial blast count greater than 1,000/microL.
      The following variables were tested to analyze response to prephase therapy: age,
      sex, evaluated risk factor (RF), blast count on day 0, actual dose of
      prednisolone administered, immunophenotype (T v non-T), and day of IT MTX. For
      statistical analysis, the variable day of IT MTX (D) was stratified into three
      groups: group 1 if D less than 2, group 2 if D > or = 2 but < or = 6, and group 3
      if D greater than 6. RESULTS: All variables tested had a significant influence on
      response to the prephase therapy. This was especially true for IT MTX: 90.4%
      responders in group 1, 76.9% in group 2, and 70% in group 3 (P < .001).
      Immunophenotype was also a major predictor of response to the prephase: 88%
      responders in B-lineage ALL versus 56.2% in T-lineage ALL. IT MTX had a
      significant influence in B-lineage ALL (96% responders in group 1, 90% in group
      2, and 79% in group 3; P < .001), whereas the influence could not be detected in
      T-lineage ALL. CONCLUSION: These results clearly demonstrate a therapeutic
      systemic effect of low doses of IT MTX in childhood ALL, and response to prephase
      therapy should not be considered as an in vivo test for cortico-sensitivity only.
      Earlier use of IT MTX leads to a higher percentage of responders.

PMID- 9164192
TI  - Common and variant gene fusions predict distinct clinical phenotypes in
      rhabdomyosarcoma.
AB  - PURPOSE: We evaluated the clinical features of the common PAX3-FKHR and variant
      PAX7-FKHR gene fusions observed in rhabdomyosarcoma. PATIENTS AND METHODS:
      Reverse-transcriptase polymerase chain reaction (RT-PCR) assays were used to
      detect the gene fusions in 34 cases of rhabdomyosarcoma. Clinical data were
      obtained retrospectively and compared with the molecular results. RESULTS: The
      PAX3-FKHR and PAX7-FKHR gene fusions were present in tumors from 18 and 16
      patients, respectively. The group with a PAX7-FKHR fusion was younger (P = .01)
      and presented more often with an extremity lesion (82% v 22%; P = .001). PAX7
      FKHR tumors were more often localized than PAX3-FKHR tumors (P = .03). In
      patients with metastatic disease at diagnosis, the patterns were different: PAX7
      FKHR patients had metastatic disease that involved only bone (n = 2) and distant
      nodes (n = 2), while the PAX3-FKHR group had multiple sites involved, including
      bone (n = 7), marrow (n = 7), lungs (n = 3), distant nodes (n = 2), skin (n = 1),
      and brain (n = 1). No significant difference in relapse rate was observed. A
      trend toward improved overall survival in the PAX7-FKHR group was noted (P =
      .09). Event-free survival for this PAX7-FKHR group was significantly longer (P =
      .04). CONCLUSION: Our results suggest that the common PAX3-FKHR and the variant
      PAX7-FKHR fusions are associated with distinct clinical phenotypes.
      Identification of fusion gene status may be a useful diagnostic tool in
      rhabdomyosarcoma.

PMID- 9164193
TI  - Importance of bleomycin in combination chemotherapy for good-prognosis testicular
      nonseminoma: a randomized study of the European Organization for Research and
      Treatment of Cancer Genitourinary Tract Cancer Cooperative Group.
AB  - PURPOSE: This prospective randomized trial was designed to compare the efficacy
      of etoposide plus cisplatin (EP) versus bleomycin, etoposide, and cisplatin (BEP)
      chemotherapy in patients with good-prognosis metastatic nonseminomatous
      testicular cancer. PATIENTS AND METHODS: Four hundred nineteen patients with good
      prognosis nonseminomatous testicular cancer were randomized to receive four
      cycles of cisplatin 20 mg/m2 on days 1 to 5 plus etoposide 120 mg/m2 on days 1,
      3, and 5 with or without bleomycin 30 mg weekly. RESULTS: Of 395 eligible
      patients, 169 of 195 patients allocated to EP (87%) and 189 of 200 patients
      allocated to BEP (95%) achieved a complete response with chemotherapy alone or
      after postchemotherapy surgery. These results are significantly different (P =
      .0075). After a median follow-up duration of 7.3 years, eight patients (4%) on
      each treatment arm relapsed. In view of the low number of unfavorable treatment
      outcomes (11%), no significant differences were detected in time to progression
      (P = .136) and survival (P = .262). Both the acute and late pulmonary toxicity
      and neurotoxicity were significantly greater in patients who received BEP,
      whereas Raynaud's phenomenon occurred exclusively in patients who received BEP (P
      < .001). Two patients treated with BEP died of bleomycin pulmonary toxicity.
      CONCLUSION: BEP is the most effective combination regimen in the treatment of
      disseminated nonseminomatous germ cell cancer. In this particular BEP regimen
      with etoposide at a dose of 360 mg/m2 per cycle, even in good-prognosis patients,
      bleomycin cannot be deleted without compromising treatment efficacy, but its use
      is associated with more toxicity (particularly pulmonary) and efforts to reduce
      this merit further exploration.

PMID- 9164194
TI  - Randomized trial of bleomycin, etoposide, and cisplatin compared with bleomycin,
      etoposide, and carboplatin in good-prognosis metastatic nonseminomatous germ cell
      cancer: a Multiinstitutional Medical Research Council/European Organization for
      Research and Treatment of Cancer Trial.
AB  - PURPOSE: This prospective randomized multicenter trial was designed to evaluate
      the efficacy of carboplatin plus etoposide and bleomycin (CEB) versus cisplatin
      plus etoposide and bleomycin (BEP) in first-line chemotherapy of patients with
      good-risk nonseminomatous germ cell tumors. PATIENTS AND METHODS: Between
      September 1989 and May 1993, a total of 598 patients with good-risk
      nonseminomatous germ cell tumors were randomized to receive four cycles of either
      BEP or CEB. In each cycle, the etoposide dose was 120 mg/m2 on days 1, 2, and 3,
      and the bleomycin dose was 30 U on day 2. BEP patients received cisplatin at 20
      mg/m2/d on days 1 to 5 or 50 mg/m2 on days 1 and 2. For CEB patients, the
      carboplatin dose was calculated from the glomerular filtration rate to achieve a
      serum concentration x time of 5 mg/mL x minutes. Chemotherapy was recycled at 21
      day intervals to a total of four cycles. RESULTS: Of patients assessable for
      response, 253 of 268 (94.4%) of those allocated to receive BEP achieved a
      complete response, compared with 227 of 260 (87.3%) allocated to receive CEB (P =
      .009). There were 30 treatment failures in the 300 patients allocated to BEP and
      79 in the 298 allocated to CEB (log-rank chi 2 = 26.9; P < .001), which led to
      failure-free rates at 1 year of 91% (95% confidence interval [CI], 88% to 94%)
      and 77% (95% CI, 72% to 82%), respectively. There were 10 deaths in patients
      allocated to BEP and 27 in patients allocated to CEB (log-rank chi 2 = 8.77; P =
      .003), which led to 3-year survival rates of 97% (95% CI, 95% to 99%) and 90%
      (95% CI, 86% to 94%), respectively. CONCLUSION: With these drug doses and
      schedules, combination chemotherapy based on carboplatin was inferior to that
      based on cisplatin. This BEP regimen that contains moderate doses of etoposide
      and bleomycin is effective in the treatment of patients with good-prognosis
      metastatic nonseminoma.

PMID- 9164195
TI  - Phase II trial of docetaxel in patients with advanced or metastatic transitional
      cell carcinoma.
AB  - PURPOSE: A phase II trial of docetaxel was conducted to assess its efficacy and
      toxicity in patients with advanced transitional-cell carcinoma (TCC) who had
      failed to respond to prior cisplatin-based therapy. PATIENTS AND METHODS: Thirty
      assessable patients who had failed to respond to or relapsed after one prior
      cisplatin-containing regimen were treated with docetaxel 100 mg/m2 over 1 hour,
      every 21 days. All patients were premedicated with dexamethasone and
      diphenhydramine to reduce allergic reactions. Reductions of subsequent doses were
      made for severe hematologic toxicity. Prophylactic hematopoietic growth factors
      were not used. RESULTS: Four of 30 patients (13.3%; 95% confidence interval [CI],
      3.8% to 30.7%) demonstrated a partial response (PR), with durations of response
      ranging from 3 to 8 months. The estimated median survival duration for all
      patients is 9 months (95% CI, 6 to 12 months) with a median follow-up time of 14
      months (range, 1 to 27). Hematologic toxicity included anemia, thrombocytopenia,
      neutropenia, and febrile neutropenia. Nonhematologic toxicity included alopecia
      and mucositis. Fluid retention was not observed and cutaneous toxicity was mild
      and infrequent. Dose reductions were necessary for adverse events in 18 patients
      (60%). CONCLUSION: Docetaxel is an active single agent in previously treated
      patients with TCC of the urothelial tract. Therapy was well tolerated in this
      patient population but myelosuppression was frequent. Further study in previously
      untreated patients, both alone and in combination, is warranted.

PMID- 9164196
TI  - Increased intensification and total dose of cyclophosphamide in a doxorubicin
      cyclophosphamide regimen for the treatment of primary breast cancer: findings
      from National Surgical Adjuvant Breast and Bowel Project B-22.
AB  - PURPOSE: The National Surgical Adjuvant Breast and Bowel Project (NSABP)
      initiated a randomized trial (B-22) to determine if intensifying but maintaining
      the total dose of cyclophosphamide (Cytoxan, Bristol-Myers Squibb Oncology,
      Princeton, NJ) in a doxorubicin (Adriamycin, Pharmacia, Kalamazoo, MI)
      cyclophosphamide combination (AC), or if intensifying and increasing the total
      dose of cyclophosphamide improves the outcome of women with primary breast cancer
      and positive axillary nodes. PATIENTS AND METHODS: Patients (N = 2,305) were
      randomized to receive either four courses of standard AC therapy (group 1);
      intensified therapy, in which the same total dose of cyclophosphamide was
      administered in two courses (group 2); or intensified and increased therapy, in
      which the total dose of cyclophosphamide was doubled (group 3). The dose and
      intensity of doxorubicin were similar in all groups. Disease-free survival (DFS)
      and overall survival were determined using life-table estimates. RESULTS: There
      was no significant difference in DFS (P = .30) or overall survival (P = .95)
      among the groups through 5 years. At 5 years, the DFS of women in group 1 was
      similar to that of women in group 2 (62% v 60%, respectively; P = .43) and to
      that of women in group 3 (62% v 64%, respectively; P = .59). The 5-year survival
      of women in group 1 was similar to that of women in group 2 (78% v 77%,
      respectively; P = .86) and to that of women in group 3 (78% v 77%, respectively;
      P = .82). Grade 4 toxicity increased in groups 2 and 3. Failure to note a
      difference in outcome among the groups was unrelated to either differences in
      amount and intensity of cyclophosphamide or to dose delays and intervals between
      courses of therapy. CONCLUSION: Intensifying or intensifying and increasing the
      total dose of cyclophosphamide failed to significantly improve either DFS or
      overall survival in any group. It was concluded that, outside of a clinical
      trial, dose-intensification of cyclophosphamide in an AC combination represents
      inappropriate therapy for women with primary breast cancer.

PMID- 9164197
TI  - High-dose chemotherapy with autologous hematopoietic stem-cell support for breast
      cancer in North America.
AB  - PURPOSE: To identify trends in high-dose therapy with autologous hematopoietic
      stem-cell support (autotransplants) for breast cancer (1989 to 1995). PATIENTS
      AND METHODS: Analysis of patients who received autotransplants and were reported
      to the Autologous Blood and Marrow Transplant Registry. Between January 1, 1989
      and June 30, 1995, 19,291 autotransplants were reviewed; 5,886 were for breast
      cancer. Main outcomes were progression-free survival (PFS) and survival. RESULTS:
      Between 1989 and 1995, autotransplants for breast cancer increased sixfold. After
      1992, breast cancer was the most common indication for autotransplant.
      Significant trends included increasing use for locally advanced rather than
      metastatic disease (P < .00001) and use of blood-derived rather than marrow
      derived stem cells (P < .00001). One-hundred-day mortality decreased from 22% to
      5% (P < .0001). Three-year PFS probabilities were 65% (95% confidence intervals
      [Cls], 59 to 71) for stage 2 disease, and 60% (95% Cl, 53 to 67) for stage 3
      disease. In metastatic breast cancer, 3-year probabilities of PFS were 7% (95%
      Cl, 4 to 10) for women with no response to conventional dose chemotherapy; 13%
      (95% Cl, 9 to 17) for those with partial response; and 32% (95% Cl, 27 to 37) for
      those with complete response. Eleven percent of women with stage 2/3 disease and
      less than 1% of those with stage 4 disease participated in national cooperative
      group randomized trials. CONCLUSION: Autotransplants increasingly are used to
      treat breast cancer. One-hundred-day mortality has decreased substantially. Three
      year survival is better in women with earlier stage disease and in those who
      respond to pretransplant chemotherapy.

PMID- 9164198
TI  - Phase II trial of biweekly paclitaxel and cisplatin in advanced breast carcinoma:
      an Eastern Cooperative Oncology Group study.
AB  - PURPOSE: To determine the efficacy of a biweekly paclitaxel and cisplatin regimen
      in patients with advanced breast carcinoma, which has previously been reported to
      produce an 85% response rate in such patients. PATIENTS AND METHODS: Sixteen
      patients with metastatic breast carcinoma who had relapsed after prior
      doxorubicin-containing adjuvant chemotherapy were treated with paclitaxel (90
      mg/m2) by intravenous (i.v.) infusion over 3 hours followed by cisplatin (60
      mg/m2) given by i.v. infusion over 1 hour on an outpatient basis. Treatment was
      repeated every 2 weeks if the absolute neutrophil count was > or = 750/microL and
      platelet count > or = 75,000/microL. After a maximum of eight cycles of
      paclitaxel/cisplatin, patients received biweekly paclitaxel alone (90 mg/m2 with
      dose escalation). Thirteen patients were assessable for response and all for
      toxicity. Nine of 13 patients assessable for response (69%) had at least three
      sites of metastases and 10 patients (77%) had visceral-dominant disease. RESULTS:
      Partial response occurred in three of 13 assessable patients (23%; 90% confidence
      interval, 7% to 49%). All responders had two or fewer sites of metastases. The
      median time to progression was 4.3 months and the median survival duration was
      11.4 months. Patients received a median of seven cycles of therapy (range, two to
      21). Severe and/or life-threatening toxicity occurred in 50% and 38%,
      respectively, and consisted primarily of granulocytopenia, anemia, and
      neuropathy. The trial was terminated after the first interim analysis as per its
      two-stage design, since it was unlikely that the response rate would exceed 70%.
      CONCLUSION: Biweekly paclitaxel/cisplatin is not likely to produce a response
      rate greater than 70% in patients with metastatic breast cancer who have relapsed
      after prior doxorubicin-containing adjuvant chemotherapy and who have multiple
      sites of metastases and/or visceral-dominant disease.

PMID- 9164199
TI  - Dose escalation of cyclophosphamide in patients with breast cancer: consequences
      for pharmacokinetics and metabolism.
AB  - PURPOSE: The alkylating anticancer agent cyclophosphamide (CP) is a prodrug that
      undergoes a complex metabolism in humans producing both active and inactive
      metabolites. In parallel, unchanged CP is excreted via the kidneys. The aim of
      this study was to investigate the influence of dose escalation on CP
      pharmacokinetics and relative contribution of activating and inactivating
      elimination pathways. PATIENTS AND METHODS: Pharmacokinetics of CP were assessed
      in 12 patients with high-risk primary breast cancer who received an adjuvant
      chemotherapy regimen that included four courses of conventional-dose CP (500
      mg/m2 over 1 hour every 3 weeks) followed by one final course of high-dose CP
      (100 mg/kg over 1 hour). Plasma concentrations of CP were analyzed by high
      performance liquid chromatography (HPLC), 24-hour urinary concentrations of CP,
      and its inactive metabolites (carboxyphosphamide, dechloroethylcyclophosphamide
      [dechlorethylCP], ketocyclophosphamide [ketoCP]) were determined by 31-phosphorus
      nuclear magnetic resonance (31P-NMR)-spectroscopy. RESULTS: There was no
      difference in dose-corrected area under the concentration-time curve (AUC) (216 v
      223 [mumol.h/[mL.g]), elimination half-life (4.8 v 4.8 hours), systemic clearance
      (79 v 77 mL/min) and volume of distribution (0.49 v 0.45 L/kg) of CP between
      conventional- and high-dose therapy, respectively. However, during high-dose
      chemotherapy, we observed a significant increase in the renal clearance of CP (15
      v 23 mL/min; P < .01) and in the formation clearance of carboxyphosphamide (7 v
      12 mL/min; P < .05) and dechloroethylCP (3.2 v 4.2 mL/min; P < .05), whereas
      metabolic clearance to ketoCP remained unchanged (1.3 v 1.2 mL/min).
      Consequently, metabolic clearance to the remaining (reactive) metabolites
      decreased from 52 to 38 mL/min (P < .001). The relative contribution of the
      different elimination pathways to overall clearance of CP demonstrated wide
      interindividual variability. CONCLUSION: Overall pharmacokinetics of CP are
      apparently not affected during eightfold dose escalation. However, there is a
      shift in the relative contribution of different clearances to systemic CP
      clearance in favor of inactivating elimination pathways, thereby indicating
      saturation of bioactivating enzymes during dose escalation. Besides individual
      enzyme capacity, hydration and concomitant medication with dexamethasone
      modulated CP disposition.

PMID- 9164200
TI  - Cyclophosphamide and fluorouracil combined with mitoxantrone versus doxorubicin
      for breast cancer: superiority of doxorubicin.
AB  - PATIENTS AND METHODS: We conducted a randomized, multicenter study of intravenous
      cyclophosphamide 500 mg/m2 plus fluorouracil 500 mg/m2 combined with either
      mitoxantrone (Novantrone, Lederle Cyanamid Canada Ltd, Willowdale, Ontario) 10
      mg/m2 (CNF) or doxorubicin (Adriamycin, Adria Laboratories of Canada Ltd,
      Mississauga, Ontario) 50 mg/m2 (CAF) every 3 weeks in advanced breast cancer.
      RESULTS: The response rate in 249 randomized patients was 36% with CNF (44 of
      121) and 48% with CAF (62 of 128) (P = .054), with complete remissions in 10
      patients (8.3%) on CNF and in 13 (10.2%) on CAF. If only fully assessable
      patients are considered, the response rate was 48% (44 of 91) with CNF and 60%
      (62 of 103) with CAF (P = .098). At time of analysis, all except 10 patients (one
      CNF and nine CAF) had died. The median survival time with CAF was longer than
      with CNF (15.2 v 10.9 months; P = .003), and time to progression was also longer
      with CAF (5.3 v 3.2 months; P < .03). Survival differences remained significant
      (P = .006) if patients who failed to meet all eligibility criteria were excluded.
      Favorable prognostic factors for survival in a Cox regression model included good
      performance status (P < .0001); less than two organ systems involved by tumor (P
      < .0001); no involvement of lung, liver, or brain (P < .003); involvement of bone
      or bone marrow (P < .009), prior surgery for breast cancer (P < .006); being
      premenopausal (P < .03); > or = 3 years from diagnosis until randomization on
      this study (P < .03); and treatment with CAF (P < .03). Alopecia > or = grade 3
      was reported in 55% of patients with CAF and 12% of patients with CNF (P < .001),
      while other > or = grade 3 toxicities did not differ significantly. Priestman
      Baum quality-of-life assessment was comparable on the two study arms. CONCLUSION:
      In patients with advanced breast cancer, CAF was associated with longer survival
      than was CNF, with an increase in alopecia, but not in other toxicities.

PMID- 9164201
TI  - Human pharmacokinetic characterization and in vitro study of the interaction
      between doxorubicin and paclitaxel in patients with breast cancer.
AB  - PURPOSE: We performed a pharmacologic investigation of paclitaxel (PTX) infused
      over 3 hours and bolus doxorubicin (DOX) to assess the role of sequence, interval
      between drugs, and duration of doxorubicin infusion on paclitaxel and
      anthracycline plasma disposition. We also explored possible mechanisms of
      pharmacokinetic interference involving the physiologic role of the multidrug
      resistance phenotype in anthracycline and taxane biliary excretion. PATIENTS AND
      METHODS: Pharmacokinetics was performed in 80 cycles and 36 women with previously
      untreated metastatic breast cancer. PTX, DOX, and their metabolites 6 alpha
      hydroxyl-PTX (6 alpha OH-PTX) and doxorubicinol (DOL) were measured by high
      pressure liquid chromatography (HPLC). Human breast cancer MCF-7 wild-type (WT)
      and resistant (TH) cell lines were cultured in whole human plasma to study
      anthracycline retention after treatment with different combinations of PTX,
      Cremophor EL (CEL) (PEG35 castor oil; BASF, Parsippany, NJ), and DOX. RESULTS:
      Pharmacokinetic interference between PTX and DOX was responsible for nonlinearity
      of DOX plasma disposition and increased concentrations of DOX and DOL. These
      effects were PTX dose-dependent, DOX concentration-dependent, and likely a result
      of interference at the level of liver elimination. In view of the physiologic
      role of P-glycoproteins (P-gp) in xenobiotic biliary excretion, retention of DOX
      was assessed in MCF-7 WT and MCF-7 TH cells. Intracellular was significantly
      higher in MCF-7 WT than MCF-7 TH (P < .05). However, concomitant exposure to DOX,
      PTX, and CEL caused similar DOX retention in both MCF-7 WT and TH cells.
      CONCLUSION: PTX, as clinically formulated in CEL, is responsible for a nonlinear
      disposition of DOX and DOL. Nonlinearity is PTX- and DOX-dependent, and possibly
      caused by competition for biliary excretion of taxanes and anthracyclines
      mediated by P-gp. Nonlinearity indicates that even minor modifications of dose
      and infusion duration of DOX and PTX may lead to unpredictable pharmacodynamic
      consequences. The postulated role of P-gp suggests that CEL is clinically active,
      and advises caution in designing combinations of PTX with other drugs that are
      substrate for P-gp.

PMID- 9164202
TI  - bcl-2, p53, and response to tamoxifen in estrogen receptor-positive metastatic
      breast cancer: a Southwest Oncology Group study.
AB  - PURPOSE: To test the hypothesis that high bcl-2 expression and accumulation of
      p53 protein, both of which should inhibit apoptosis, are associated with a poorer
      tamoxifen response and a more aggressive clinical course in estrogen receptor
      (ER)-positive metastatic breast cancer. METHODS: A total of 205 paraffin-embedded
      tumor blocks were evaluated for nuclear p53 (a marker of p53 inactivation) and
      cytoplasmic bcl-2 by immunohistochemistry (IHC). All patients received tamoxifen
      as initial therapy for metastatic disease. The study began in 1982 and follow-up
      duration of the 24 patients last known alive is 8 years. RESULTS: Response to
      tamoxifen and time to treatment failure (TTF) were not significantly associated
      with p53 status, although patients with higher p53 had a worse survival (P =
      .008; median, 36 v 20 months). Higher bcl-2 expression was associated with higher
      levels of ER (P = .02), better response to tamoxifen (62% v 49%; P = .07), longer
      TTF (median, 9 v 5 months; P = .002), and better survival (median, 40 months v 25
      months; P = .009). In multivariate analyses, including ER, progesterone receptor
      (PgR), and p53, high bcl-2 remained significantly associated with a longer TTF (P
      = .007) and survival (P = .07). p53 status was a significant factor for shorter
      survival (P = .05), but not for TTF (P = .61). CONCLUSION: p53 status, as
      determined by IHC is not significantly associated with response to tamoxifen,
      although tumors with altered p53 protein are inherently more aggressive. Contrary
      to expectation, high bcl-2 identifies a relatively indolent phenotype of ER
      positive metastatic breast cancer, in which patients experience a better clinical
      response to tamoxifen and a longer survival.

PMID- 9164203
TI  - Prognostic importance of thymidylate synthase expression in early breast cancer.
AB  - PURPOSE: To assess the prognostic importance of thymidylate synthase (TS)
      expression in breast tumors of patients with early-stage breast cancer, and to
      determine whether the benefit of chemotherapy (CT) is associated with TS
      expression. PATIENTS AND METHODS: The level of TS expression was evaluated in 210
      node-negative and 278 node-positive patients enrolled onto Trial V of the
      International Breast Cancer Study Group ([IBCSG] formerly the Ludwig Breast
      Cancer Study Group) with a median follow-up time of 8.5 years. TS expression was
      assessed using the immunohistochemical method with the monoclonal antibody TS 106
      on paraffin-embedded tissue specimens. RESULTS: High TS expression was associated
      with a significantly worse prognosis in node-positive but not in node-negative
      breast cancer patients. Twenty-seven percent of node-positive patients with high
      TS expression were disease-free at 10 years, compared with 44% of node-positive
      patients with low TS expression (P = .03). Forty-one percent of patients with
      node-positive high-TS-expressing tumors were alive after 10 years, compared with
      49% of those with low TS expression (P = .06). The association between TS and
      disease-free survival (DFS) and overall survival (OS) was independent of other
      prognostic factors such as tumor size, tumor grade, nodal status, vessel
      invasion, estrogen receptor (ER)/ progestin receptor (PR) status, c-erb B-2, or
      Ki-67 expression. In node-positive patients, six cycles of standard adjuvant
      cyclophosphamide, methotrexate, and fluorouracil ([5-FU] CMF) CT improved DFS and
      OS compared with one cycle of perioperative CMF therapy. The magnitude of this
      benefit was greatest in patients whose tumors had high TS expression (P < .01 for
      DFS; P < .01 for OS). Node-negative patients demonstrated no difference in
      outcome to CT based on TS expression; however, the power to detect differences
      was limited by the small number of events in this group. CONCLUSION: In early
      stage breast cancer, high TS expression is associated with a significantly worse
      prognosis in node-positive patients. Node-positive patients with high TS levels
      demonstrate the most significant improvement in DFS and OS when treated with six
      cycles of conventional adjuvant CMF therapy.

PMID- 9164204
TI  - Differential expression of telomerase activity in human cervical cancer and
      cervical intraepithelial neoplasia lesions.
AB  - PURPOSE: Telomeres are tandem arrays of repeated DNA sequences located at the
      ends of eukaryotic chromosomes, and are synthesized by the enzyme telomerase.
      Loss of telomeric DNA may play an important role in the development of human
      cancers. However, very little is known about the status of telomerase during
      human cervical cancer development. PATIENTS AND METHODS: Telomerase activity was
      measured by telomere repeat amplification protocol (TRAP) assay in 24 cervical
      cancers, one carcinoma in situ (CIS), and 20 cervical intraepithelial neoplasia
      (CIN) lesions. Adjacent nontumor cervical tissue from the same 24 cervical cancer
      patients and normal cervical tissues from 11 control individuals also were
      examined for the presence of telomerase activity. RESULTS: Twenty two of the 24
      (91.7%) cervical cancer specimens and the single CIS tissue were strongly
      positive for telomerase activity. Relatively weak but distinctive telomerase
      activity also was detectable in one of four CIN-I (25%), two of eight CIN-II
      (25%), and two of eight CIN-III (25%), respectively. However, telomerase activity
      was not found in the 24 corresponding nontumor cervical tissues from the same
      cervical cancer patients and the 11 normal cervical tissues from control
      individuals. CONCLUSION: The majority of cervical cancers contain strong
      telomerase activity. Significant proportions of noncancerous CIN tissues also
      contain telomerase activity, although weaker than that in cervical cancer. It
      seems that there is a progressive increase of telomerase activity in association
      with an increased degree of cervical malignancy. These results seem to suggest
      that the expression of telomerase may play a crucial role in cervical cancer
      carcinogenesis.

PMID- 9164205
TI  - Weekly cisplatin given for 2 months versus cisplatin plus cyclophosphamide given
      for 5 months after cytoreductive surgery for advanced ovarian cancer.
AB  - PURPOSE: To compare the efficacy of a treatment with cisplatin plus
      cyclophosphamide given for 5 months and a short treatment with cisplatin alone in
      advanced ovarian cancer, we conducted a multicenter randomized clinical trial.
      PATIENTS AND METHODS: Eligibility criteria were as follows: first diagnosis of
      histologically confirmed invasive epithelial ovarian cancer of International
      Federation of Gynecology and Obstetric (FIGO) stage III-IV, age younger than 75
      years, and Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or
      2. Within 28 days of cytoreductive surgery, eligible women were randomly assigned
      treatment with weekly cisplatin 50 mg/m2 for nine courses or cisplatin 75 mg/m2
      plus cyclophosphamide 750 mg/m2 every 21 days for six courses. RESULTS: A total
      of 607 women were entered onto the study. There was no difference in the response
      to treatment. Pathologic complete response (CR) was documented in 63 of the
      weekly cisplatin cases and 70 of the cisplatin plus cyclophosphamide group (chi
      1(2) = 1.43; P = .23). The median follow-up time was 3 years. There were 151 and
      148 deaths in the weekly cisplatin and cyclophosphamide plus cisplatin arms,
      respectively. Survival curves were similar in the two groups, with a 3-year
      percent survival estimate of 44.1 (SE = 3.4) in the weekly cisplatin and 44.6 (SE
      = 3.4) in the cisplatin plus cyclophosphamide group (log-rank test chi 1(2) =
      0.004; P = .96). CONCLUSION: This study found that 2-month monochemotherapy
      treatment with cisplatin was as effective as 5-month polychemotherapy including
      cisplatin at a similar doses but different dose-intensity plus cyclophosphamide.

PMID- 9164206
TI  - Pharmacokinetic and phase I trial of intraperitoneal carboplatin and cyclosporine
      in refractory ovarian cancer patients.
AB  - PURPOSE: The feasibility and pharmacokinetics of cyclosporine (CsA) delivered
      intraperitoneally (IP) have not been previously explored. We performed a
      pharmacokinetic study of IP CsA followed by a phase I dose-escalation trial of
      the combination of IP CsA and carboplatin in refractory ovarian cancer patients.
      PATIENTS AND METHODS: A pilot study was performed of three patients who received
      1, 10, and 20 mg/kg IP CsA alone. Subsequently, a phase I trial of 35 patients
      was performed between April 1990 and April 1993. Whole-blood and IP fluid CsA
      concentrations were measured at serial time points. The highest dose delivered IP
      was 34.6 mg CsA/kg in combination with carboplatin (250 mg/m2 or 300 mg/m2,
      depending on creatinine clearance), which was not dose-escalated. The area under
      the concentration-time curve (AUC) for CsA and half-life (T1/2) were calculated.
      Objective and serologic responses were noted, and toxicity was graded using the
      National Cancer Institute common toxicity criteria. RESULTS: The feasibility of
      delivering IP CsA alone was established. We observed a 1,000:1 ratio between IP
      fluid and blood concentrations at 20 mg CsA/kg. Pharmacokinetic analysis
      confirmed that at 20 mg CsA/kg, there was an IP fluid-to-blood AUC ratio of 600:1
      in favor of peritoneal exposure. At the highest dose delivered, 34.6 mg CsA/kg,
      the mean IP CsA levels of 1,110 micrograms/ mL were tolerated moderately well and
      the IP fluid-to-blood ratio of 1,000:1 was maintained. Blood and IP CsA
      concentrations were analyzed in the presence and absence of IP carboplatin. At 20
      mg CsA/kg, there was no difference in either mean blood CsA levels (0.9
      microgram/ mL) or mean IP CsA concentrations (1,000 micrograms/mL) obtained in
      the absence or presence of carboplatin. The most common toxicity in the phase I
      study was anemia, seen in 66% of patients. Common toxicities at the maximum CsA
      dose delivered (34.6 mg/kg) were anemia, leukopenia, thrombocytopenia, and
      hypertension. In this trial, three objective responses (two complete and one
      partial) were observed for a duration of 3 to 11 months. Control of platinum
      resistant ascites was an important feature, noted in five of eight patients.
      CONCLUSION: We have established the feasibility of delivering IP CsA up to doses
      of 34.6 mg/kg in conjunction with carboplatin, and the sustaining of IP fluid to
      blood ratios of 1,000:1. The IP administration of CsA resulted in a favorable
      ratio of exposure for the peritoneal cavity compared with systemic exposure,
      indicating a therapeutic advantage of this approach with a significant decrease
      in systemic toxicity. We recommend that 34.6 mg/ kg of IP CsA be tested as a
      phase II dose in combination with carboplatin in refractory ovarian cancer
      patients. This report provides the groundwork for future studies using IP CsA,
      both as a chemomodulator of platinum and of multidrug resistance.

PMID- 9164207
TI  - Phase I and pharmacologic study of the combination paclitaxel and carboplatin as
      first-line chemotherapy in stage III and IV ovarian cancer.
AB  - PURPOSE: To determine the maximum-tolerated dose for the combination paclitaxel
      and carboplatin administered every 4 weeks and to gain more insight into the
      pharmacokinetics and pharmacodynamics of this combination in previously untreated
      ovarian cancer patients. PATIENTS AND METHODS: Thirty-five chemotherapy-naive
      patients with suboptimally debulked stage III (tumor masses > 3 cm) and stage IV
      ovarian cancer were entered onto this phase I trial in which paclitaxel was
      administered as a 3-hour intravenous (IV) infusion at dosages of 125 to 225 mg/m2
      immediately followed by carboplatin over 30 minutes at dosages of 300 to 600
      mg/m2. A total of six courses was planned, followed by a second-look
      laparoscopy/laparotomy. Patients with a response and/or minimal residual disease
      at second-look laparoscopy received three additional courses. Twenty-six patients
      participated in the pharmacokinetic part of the study. RESULTS: The most
      important hematologic toxicity encountered was neutropenia. Neutropenia was more
      pronounced for the higher dose levels (DLs) and was cumulative. Thrombocytopenia
      was mild in the first eight DLs, but increased during the treatment courses.
      Nonhematologic toxicities consisted mainly of vomiting, neuropathy, fatigue,
      rash, pruritus, myalgia, and arthralgia. Dose-limiting toxicities (DLTs) in this
      trial were neutropenic fever, thrombocytopenia that required platelet
      transfusions, and cumulative neuropathy. Of 33 patients assessable for response,
      26 major responders (78%, 20 complete response [CR] and six partial response
      [PR]) were documented. The maximal concentration (Cmax) of paclitaxel and the
      area under the concentration-time curve (AUC) were not different from the
      historical data for paclitaxel as a single agent. Retrospective analysis using a
      modified Calvert formula showed that the measured carboplatin AUCs in plasma
      ultrafiltrate (pUF) were 30% +/- 3.4% less than the calculated carboplatin AUC.
      Neutropenia was more pronounced than could be expected on the basis of the
      historical times above a threshold concentration greater than 0.1 mumol/L (T > or
      = 0.1 mumol/L) or 0.05 mumol/L (T > or = 0.05 mumol/L), and thrombocytopenia was
      less than could be expected from historical sigmoidal Emax models. CONCLUSION:
      The combination of paclitaxel 200 mg/ m2 and carboplatin 550 mg/m2 every 4 weeks
      is a well-tolerated treatment modality. The paclitaxel-carboplatin combination is
      highly active in stage III (bulky) and stage IV ovarian cancer. No indications
      for a pharmacokinetic drug-drug interaction between carboplatin and paclitaxel
      were found.

PMID- 9164208
TI  - Phase I dose escalation of paclitaxel in patients with advanced ovarian cancer
      receiving cisplatin: rapid development of neurotoxicity is dose-limiting.
AB  - PURPOSE: To determine the maximum-tolerable dose (MTD) of paclitaxel in a phase I
      dose-escalation study when combined with cisplatin in patients with advanced
      ovarian cancer receiving filgrastim for prophylaxis of myelosuppression. PATIENTS
      AND METHODS: A total of 23 patients with stage II (bulky residual), III, or IV
      epithelial ovarian cancer were treated (following debulking surgery) with
      paclitaxel as a 3-hour infusion followed by cisplatin (75 mg/m2) administered
      over 4 hours on day 1, repeated every 21 days for six cycles. Filgrastim (5
      micrograms/kg/d) was administered subcutaneously (SC) beginning on day 2 of each
      cycle through neutrophil recovery (absolute neutrophil count [ANC] >
      10,000/microL). Patients were assigned to one of six escalating dose levels of
      paclitaxel: 150 (n = 3), 175 (n = 3), 200 (n = 3), 225 (n = 4), 250 (n = 4), and
      275 mg/m2 (n = 6). RESULTS: At each paclitaxel dose level (150, 175, 200, 225,
      250, and 275 mg/m2), the numbers of patients who completed six cycles without
      dose reduction were three (100%), three (100%), two (66%), two (50%), three
      (75%), and zero (0%), respectively. The numbers of patients who experienced a
      grade III/IV adverse event (hematologic or nonhematologic) were zero (0%), two
      (66%), two (66%), one (25%), four (100%), and five (80%), respectively. Reasons
      for dose reduction included neurotoxicity (225 mg/m2, n = 1; 275 mg/m2, n = 2),
      neutropenia (225 mg/m2, n = 2), diarrhea (275 mg/m2, n = 2), and nephrotoxicity
      (225 mg/m2, n = 1). Reasons for not completing six cycles at full or reduced dose
      included neuropathy (200, 225, and 275 mg/m2, n = 1 each) physician request (275
      mg/m2, n = 1), and death (275 mg/m2, n = 1). Hematopoietic toxicity was minimal.
      Six patients developed grade III/IV neutropenia. No patient developed
      thrombocytopenia below a level of 50,000/microL. CONCLUSION: The MTD of
      paclitaxel was determined to be 225 mg/m2 when administered as a 3-hour infusion
      and combined with cisplatin (75 mg/m2). Nonhematologic dose-limiting toxicities
      were neuropathy and diarrhea. The neuropathy often had a rapid onset, especially
      at the higher dose levels.

PMID- 9164209
TI  - Phase I and pharmacologic study of penclomedine, a novel alkylating agent, in
      patients with solid tumors.
AB  - PURPOSE: To determine the maximum-tolerated dose (MTD), principal toxicities, and
      pharmacologic behavior of penclomedine, a novel alkylating agent. PATIENTS AND
      METHODS: Penclomedine (45 to 550 mg/ m2/d every 3 weeks) was administered as a 1-
      or 3-hour intravenous (IV) infusion for 5 consecutive days to patients with solid
      tumors. RESULTS: On a 1-hour dosing schedule, ataxia, vertigo, nystagmus, and a
      motor aphasia were the principal toxicities of penclomedine. These neurologic
      effects were dose-related, and evolved from complaints of somnolence and
      dizziness, to more pronounced signs and symptoms of cerebellar dysfunction. Up to
      and including doses of 415 mg/m2, these effects were well tolerated and resolved
      within 2 hours posttreatment. In contrast, both patients treated at the 550-mg/m2
      dose level experienced a dose-limiting constellation of perinfusional aphasia and
      vertigo, with either ataxia of over 2 weeks' duration or recurrent dizziness.
      Prolongation of the infusion duration to 3 hours at this dose level resulted in
      less neurotoxicity; however, delayed trilineage hematologic toxicity precluded
      timely administration on this schedule. A statistically significant relationship
      was demonstrated between the development of ataxia and maximum plasma
      concentrations of penclomedine. CONCLUSION: Neurotoxicity was the dose-limiting
      toxicity (DLT) of penclomedine administered as a 1-hour infusion daily for 5 days
      every 3 weeks, and the recommended dose for further evaluations was 415 mg/m2.
      The nature of the principal toxicities and the lack of any detectible antitumor
      activity indicate that phase II evaluations of penclomedine on this
      administration schedule should be focused on specific disease settings, such as
      breast cancer and intracerebral tumors, in which antitumor activity has been
      demonstrated.

PMID- 9164210
TI  - Phase I trial of micronized formulation carboxyamidotriazole in patients with
      refractory solid tumors: pharmacokinetics, clinical outcome, and comparison of
      formulations.
AB  - PURPOSE: Cytostatic agents targeted against angiogenesis and tumor cell invasive
      potential form a new class of investigational drugs. Orally administered
      carboxyamidotriazole (CAI) (NSC609974) is both antiangiogenic and antimetastatic.
      An encapsulated micronized powder formulation has been developed to optimize CAI
      administration. A phase I dose escalation trial with pharmacokinetic analysis has
      been performed. PATIENTS AND METHODS: Twenty-one patients with refractory solid
      tumors and good end organ function and performance status were enrolled onto the
      study. Patients received a test dose followed 1 week later by daily
      administration of CAI in the encapsulated micronized formulation at doses of 100
      to 350 mg/m2. Patients remained on CAI until disease progression or dose-limiting
      toxicity. Plasma samples were taken to characterize the pharmacokinetic
      parameters of this formulation of CAI. RESULTS: All patients were assessable for
      toxicity and 18 were assessable for pharmacokinetics and response analysis. Grade
      1 and 2 gastrointestinal side effects were observed in up to 50% of patients.
      Dose-limiting toxicity was observed in both patients treated at 350 mg/m2/d,
      consisting of reversible grade 2 to 3 cerebellar ataxia (n = 1) and confusion (n
      = 1). One minor response (MR) was observed in a patient with renal cell carcinoma
      and another nine patients had disease stabilization (MR + SD = 47%).
      Pharmacokinetic analysis demonstrated reduced bioavailability (58% reduction)
      compared with the PEG-400 liquid formulation previously reported. CONCLUSION: The
      better toxicity profile of encapsulated micronized CAI with similar frequency of
      disease stabilization and ease of administration compared with the liquid or
      gelatin capsule, suggests that the micronized formulation is a preferable
      formulation for subsequent studies. A dose of 300 mg/m2/d is proposed for phase
      II investigations.

PMID- 9164212
TI  - Cell proliferation-related markers in colorectal liver metastases: correlation
      with patient prognosis.
AB  - PURPOSE: We analyzed the relation between phenotypic (DNA ploidy) and functional
      markers (S-phase cell fraction, p53, and bcl-2 protein expression) and defined
      their relevance on clinical outcome on a retrospective series of radically
      resected liver metastases from colorectal cancer. PATIENTS AND METHODS: Among 104
      patients with resectable liver metastases from colorectal cancer, DNA ploidy was
      determined by flow cytometry, 3H-thymidine labeling index (TLI) by
      autoradiography, and expression of p53 and bcl-2 by immunohistochemistry.
      RESULTS: TLI was a significant indicator for relapse at 4 years from radical
      surgery, DNA ploidy was a suggestive indicator of clinical outcome, and p53 and
      bcl-2 expression provided no clinical information. By multivariate analysis, cell
      proliferation rate and Dukes' stage remained independent prognostic parameters.
      In the most representative subgroup of patients with H1 liver lesions (86 cases),
      TLI was always associated with relapse, and DNA ploidy and p53 expression
      provided discriminant information within slowly proliferating liver lesions.
      CONCLUSION: Tumor-cell proliferation of liver lesions should be used with stage
      of the primary colorectal cancer for a more accurate prognosis in patients
      submitted to curative hepatic resection.

PMID- 9164213
TI  - Prognostic factors in adenocarcinoma of the gastric cardia: pathologic stage
      analysis and multivariate regression analysis.
AB  - PURPOSE: To clarify the pathologic stages of adenocarcinoma of the gastric cardia
      in which the prognosis is worse than in adenocarcinoma of the middle or distal
      part of the stomach, and to determine prognostic factors in these stages by
      multivariate analysis. PATIENTS AND METHODS: We analyzed 2,536 cases of
      surgically resected gastric adenocarcinoma of all pathologic stages. Four hundred
      seventy-two cases of gastric carcinoma, in which cumulative survival of gastric
      cardia was poor, were subjected to Cox regression analysis for prognostic
      factors, and to logistic regression analysis for factors influencing venous or
      lymphatic invasion. RESULTS: The prognosis of adenocarcinoma of the gastric
      cardia was inferior when compared with similarly staged carcinomas of the middle
      or lower part of the stomach when there was invasion of proper muscle layer or
      subserosal layer, with no lymph node metastasis or with only adjacent (group 1)
      lymph nodes metastases (T2N0 or T2N1, according to the Japanese classification).
      In these stages, the prognostic factors were age, histologic type, venous
      invasion, and location of the tumor in the upper part of the stomach. Tumor
      location in the upper stomach was also a predictor for the presence of venous
      invasion. CONCLUSION: The prognosis of adenocarcinoma of the gastric cardia is
      poor in patients with T2 tumors with no or few lymph node metastases. Additional
      treatment after surgery may be necessary to improve the survival of this
      population.

PMID- 9164211
TI  - Superantigen-based immunotherapy: a phase I trial of PNU-214565, a monoclonal
      antibody-staphylococcal enterotoxin A recombinant fusion protein, in advanced
      pancreatic and colorectal cancer.
AB  - PURPOSE: To establish the maximum-tolerated dose (MTD) and define the toxicities
      of a single-dose infusion of PNU-214565, a recombinant Escherichia coli-derived
      fusion protein of Staphylococcal enterotoxin A (SEA) and the Fab-fragment of the
      C242 monoclonal antibody in patients with advanced colorectal and pancreatic
      carcinomas. To investigate the capability of PNU-214565 to induce a superantigen
      (SAg) response resulting in cytokine production and tumor regression. PATIENTS
      AND METHODS: Twenty-one patients (age range, 39 to 76 years; median, 64; 12 men,
      nine women; 18 colorectal, three pancreatic cancers) were treated with a single 3
      hour infusion of PNU-214565, with doses ranging from 0.01 to 1.5 ng/kg. All
      patients had prior chemotherapy and a good performance status Eastern Cooperative
      Oncology Group [ECOG] performance status [PS] = 0 [n = 10]; PS = 1 [n = 11]), 10
      had prior radiation, and 18 had prior surgery. RESULTS: Fever and hypotension
      were the most common toxicities. Fever of any grade occurred in 16 of 21 patients
      (76%): four of 21 (19%) with grade 2 and two of 21 (9.5%) with grade 3.
      Hypotension of any grade occurred in 13 of 21 (62%): four of 21 with grade 2 and
      one of 21 (5%) with grade 3. Interleukin-2 (IL-2) and tumor necrosis factor alpha
      (TNF alpha) induction correlated with toxicity. In the two patients with grade 3
      fever, peak IL-2 and TNF alpha levels were 2.9 IU/mL and 165 pg/mL, and 8.3 IU/mL
      and 245 pg/mL, respectively. Transient, > or = 50% decreases in circulating
      monocytes were observed in 17 of 21 patients as early as 0.5 hours (median time,
      2 hours) from the start of infusion. Decreases (mean 33%) in circulating
      lymphocytes were observed in seven of 21 patients. All three patients with grade
      3 toxicity were treated at the 0.5-ng/kg dose. The significance of baseline anti
      SEA, human antimouse antibody (HAMA), CA242-soluble antigen levels, and T-cell
      receptor variable beta region (TCR V beta) subsets and histocompatibility
      leukocyte antigen-DR (HLA-DR) genotypes was assessed as possible predictors of
      toxicity. All toxicities were transient and easily managed. No grade 3 toxicity
      occurred at the higher dose levels. CONCLUSION: PNU-214565, a SAg-based tumor
      targeted therapy, is safe when given as a single 3-hour infusion at doses up to
      1.5 ng/kg. The MTD for a single dose was not determined. The safety of a repeated
      dose schedule is currently under investigation, beginning with doses determined
      to be safe in this trial.

PMID- 9164214
TI  - Effect of regional and systemic fluorinated pyrimidine chemotherapy on quality of
      life in colorectal liver metastasis patients.
AB  - PURPOSE: Since systemic and regional (HAI) fluorinated pyrimidine chemotherapies
      offer similar survival benefit in treatment of colorectal liver metastases (CLM),
      we sought to identify their impact on quality of life (QoL), which might be a
      useful indicator of treatment preference. METHODS: We compared QoL in 135 CLM
      patients managed by symptom control (n = 49 patients), systemic fluorouracil
      (5FU)/folinic acid (n = 35), or hepatic arterial floxuridine (FUDR) (n = 51).
      Full blood count and liver function tests, World Health Organization (WHO)
      toxicity criteria, and QoL (Rotterdam Symptom Checklist [RSC], the Sickness
      Impact Profile [SIP], and the Hospital Anxiety and Depression scale [HAD]) were
      measured monthly in all patients. RESULTS: The HAD anxiety score was
      significantly increased in symptom control compared with chemotherapy patients 1
      month after randomization. There was a significant increase in RSC physical score
      (repeated measures, P = .05), and in scores for sore mouth (P < .01), dry mouth
      (P < .01), and tingling hands and feet (P < .01) in systemic chemotherapy
      compared with symptom control patients. Significant QoL differences (repeated
      measures and Mann-Whitney U [MWU]) between HAI and symptom control patients were
      not detected. Systemic chemotherapy patients lived for significantly longer (log
      rank test, P < or = .0001) with abnormal HAD anxiety, RSC psychosocial, or RSC
      sore mouth scores compared with HAI patients, but there were no overall survival
      differences. CONCLUSION: Randomization to symptom control only was associated
      with increased anxiety. QoL with systemic chemotherapy was impaired by side
      effects. HAI was associated with similar survival to systemic chemotherapy but
      with better sustained QoL.

PMID- 9164215
TI  - Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic
      radiation therapy for rectal cancer: initial results of intergroup 0114.
AB  - PURPOSE: The combination of radiation therapy with fluorouracil (5-FU)-based
      chemotherapy is generally accepted as appropriate postoperative therapy for
      patients with adenocarcinomas of the rectum that extend through the bowel wall or
      with lymph nodes positive for tumor. We attempted to determine whether the
      efficacy of this postoperative therapy could be improved by the addition of
      leucovorin and/or levamisole. METHODS: A total of 1,696 patients were randomized
      and eligible for treatment with one of four treatment schemes. All patients
      received two cycles of bolus 5-FU-based systemic chemotherapy followed by pelvic
      radiation therapy with chemotherapy and two more cycles of the same systemic
      chemotherapy. Chemotherapy was either 5-FU alone, 5-FU with leucovorin, 5-FU with
      levamisole, or 5-FU with leucovorin and levamisole. RESULTS: With a median follow
      up duration of 48 months, there is no statistically significant advantage to any
      of the treatment regimens compared with bolus 5-FU alone. There is evidence of
      increased gastrointestinal toxicity with the three-drug combination compared with
      bolus 5-FU alone. Statistical analysis suggests it is very unlikely that either
      levamisole-containing combination will be shown to be of value with further
      follow-up evaluation. CONCLUSION: There is no evidence at present for a
      beneficial effect of levamisole in the adjuvant treatment of rectal cancer.
      Definitive evaluation of the effect of the addition of leucovorin to 5-FU and
      pelvic radiation will require further follow-up evaluation.

PMID- 9164217
TI  - Why has induction chemotherapy for advanced head and neck cancer become a United
      States community standard of practice?
AB  - PURPOSE: Induction chemotherapy for advanced head and neck (H&N) cancer has been
      studied in clinical trials for more than two decades without clear demonstration
      of benefit for locoregional tumor control or overall patient survival.
      Nonetheless, its use has become a common community standard of practice in the
      United States (US). This report examines some of the factors that may have
      contributed to this phenomenon. MATERIALS AND METHODS: A mail survey was
      conducted of 300 US community cancer specialists (equally divided among
      otolaryngologists, radiation oncologists, and medical oncologists) to solicit
      their most frequent therapy approach for patients with locoregionally advanced,
      nonmetastatic H&N cancer. The rationale for selection of treatment strategy was
      identified by each respondent. RESULTS: Two hundred eighteen physicians (73%)
      completed and returned the survey, representing 47 US states. The single most
      common treatment approach reported for patients with locoregionally advanced H&N
      cancer was that of sequential chemoradiation (61%), specifically, induction
      chemotherapy with fluorouracil (5-FU)/cisplatin followed by radiation therapy.
      Four percent of respondents indicated that induction chemotherapy was
      administered within the context of a controlled clinical trial, whereas 96%
      indicated that therapy was administered off study. The primary objectives cited
      by respondents for the use of induction chemotherapy included the desire to
      improve locoregional tumor control (67%), to improve overall survival (56%), to
      maintain a spirit of multidisciplinary care (34%), to improve quality of life
      (29%), and to decrease distant metastases (26%). CONCLUSION: Review of the
      published trials between 1970 and 1995 and of the published meta-analyses show no
      clear evidence for an improvement in locoregional tumor control or survival for
      H&N cancer patients treated with 5-FU/cisplatin induction chemotherapy regimens.
      Nonetheless, this induction chemotherapy approach for advanced H&N cancer
      patients has become a dominant community practice in the US. Factors that may
      have contributed to this paradox are reviewed.

PMID- 9164216
TI  - Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in
      the treatment of locally advanced anal cancer: results of a phase III randomized
      trial of the European Organization for Research and Treatment of Cancer
      Radiotherapy and Gastrointestinal Cooperative Groups.
AB  - PURPOSE: To investigate the potential gain of the concomitant use of radiotherapy
      and chemotherapy in improving local control and reducing the need for colostomy,
      a randomized phase III trial was performed in patients with locally advanced anal
      cancer. MATERIALS AND METHODS: From 1987 to 1994, 110 patients were randomized
      between radiotherapy alone and a combination of radiotherapy and chemotherapy.
      The patients had T3-4NO-3 or T1-2N1-3 anal cancer. Radiotherapy consisted of 45
      Gy given in 5 weeks, with a daily dose of 1.8 Gy. After a rest period of 6 weeks,
      a boost of 20 or 15 Gy was given in case of partial or complete response,
      respectively. Surgical resection as part of the primary treatment was performed
      if possible in patients who had not responded 6 weeks after 45 Gy or with
      residual palpable disease after the completion of treatment. Chemotherapy was
      given during radiotherapy: 750 mg/m2 daily fluorouracil as a continuous infusion
      on days 1 to 5 and 29 to 33, and a single dose of mitomycin 15 mg/m2 administered
      on day 1. RESULTS: The addition of chemotherapy to radiotherapy resulted in a
      significant increase in the complete remission rate from 54% for radiotherapy
      alone to 80% for radiotherapy and chemotherapy, and from 85% to 96%,
      respectively, if results are considered after surgical resections. This led to a
      significant improvement of locoregional control and colostomy-free interval (P =
      .02 and P = .002, respectively), both in favor of the combined modality
      treatment. The locoregional control rate improved by 18% at 5 years, while the
      colostomy-free rate at that time increased by 32% by the addition of chemotherapy
      to radiotherapy. No significant difference was found when severe side effects
      were considered, although anal ulcers were more frequently observed in the
      combined-treatment arm. The survival rate remained similar in both treatment
      arms. Skin ulceration, nodal involvement, and sex were the most important
      prognostic factors for both local control and survival. These remained
      significant after multivariate analysis. The improvement seen in local control by
      adding chemotherapy to radiotherapy also remained significant after adjusting for
      prognostic factors in the multivariate analysis. Event-free survival, defined as
      free of locoregional progression, no colostomy, and no severe side effects or
      death, showed significant improvement (P = .03) in favor of the combined
      treatment modality. The 5-year survival rate was 56% for the whole patient group.
      CONCLUSION: The concomitant use of radiotherapy and chemotherapy resulted in a
      significantly improved locoregional control rate and a reduction of the need for
      colostomy in patients with locally advanced anal cancer without a significant
      increase in late side effects.

PMID- 9164218
TI  - Poorly differentiated carcinoma and poorly differentiated adenocarcinoma of
      unknown origin: favorable subsets of patients with unknown-primary carcinoma?
AB  - PURPOSE: The objectives of this study were to assess clinical outcomes and
      prognostic factors in unselected, consecutive patients with poorly differentiated
      carcinoma (PDC) or poorly differentiated adenocarcinoma (PDA). PATIENTS AND
      METHODS: The 1,400 patients analyzed were referred to our unknown-primary tumor
      (UPT) clinic from January 1, 1987 through July 31, 1994. Clinical data from these
      patients were entered into a computerized data base for storage, retrieval, and
      analysis. Survival was measured from the time of diagnosis; survival distribution
      was estimated using the product-limit method. Multivariate survival analyses were
      performed using proportional hazards regression and by recursive partitioning.
      RESULTS: Nine hundred seventy-seven patients were diagnosed with unknown-primary
      carcinoma (UPC) and 337 of these patients had PDC or PDA. No clinical differences
      were identified among patients with PDC, PDA, or UPC patients with other
      carcinoma or adenocarcinoma subtypes. PDC patients enjoyed better survival than
      PDA patients. Poor cellular differentiation was not an important prognostic
      variable. Variables predictive of survival included lymph node metastases, sex,
      number of metastatic sites, histology (PDC v PDA), and age. Although chemotherapy
      did not appear to influence survival for the entire group of PDC or PDA patients,
      a subset of patients with good prognostic features experienced median survival
      durations of up to 40 months. CONCLUSION: The long median survival and
      chemotherapy responsiveness of UPC patients with PDC and PDA could not be
      confirmed. However, subpopulations with prolonged median survival durations could
      be defined, and the value of chemotherapy in this group remains to be determined.
      Identification and exclusion of treatable or slow-growing malignancies may
      account for the poor survival of the PDC and PDA patients reported in this study.

PMID- 9164219
TI  - Survival of differentiated thyroid carcinoma studied in 500 patients.
AB  - PURPOSE: To analyze the factors that influence survival of patients with
      differentiated thyroid carcinoma treated by surgical thyroidectomy, radioactive
      iodine, and early surgical reintervention with compartment-oriented
      lymphadenectomy in the case of locoregional recurrence. METHODS: The survival of
      500 patients with differentiated thyroid carcinoma was analyzed retrospectively
      with regard to mortality and survival rate (Kaplan-Meier). A total of 301
      patients had papillary and 199 follicular thyroid carcinoma. The mean age of the
      380 women and 120 men was 46.8 +/- 16.4 years at presentation. All patients were
      treated by surgical thyroidectomy, high-dose radioactive iodine, and early
      surgical reintervention with compartment-oriented lymphadenectomy in cases of
      locoregional recurrence, without routine adjuvant external radiotherapy of the
      neck. Patients were monitored up to 23 years, with a median follow-up time of 5.6
      years. RESULTS: Twenty-nine of 500 patients died, 19 of thyroid cancer. The
      corrected overall 5-year survival rate (Kaplan-Meier) was 0.92. Among patients
      with tumor stage pT1-3NO-1MO (low risk), none died of thyroid carcinoma (5-year
      survival rate, 0.97); in patients with tumor stage pT4 and/or M1 (high risk), the
      5-year survival rate was 0.83. The cause of death was locoregional recurrence in
      eight and metastatic disease in 11. Using multivariate analysis, risk factors
      that significantly influence survival were local invasion (pT4), metastatic
      disease (M1), and age. CONCLUSION: In differentiated thyroid carcinoma, the use
      of total surgical thyroidectomy followed by high-dose radioiodine therapy and
      early surgical reintervention in case of locoregional recurrence yields high
      survival rates, even without adjuvant external radiotherapy of the neck.

PMID- 9164220
TI  - Prospective study of postoperative magnetic resonance imaging in patients with
      malignant gliomas.
AB  - PURPOSE: We studied the natural history of postoperative enhancement on magnetic
      resonance (MR) scans in patients with malignant glioma to determine the
      following: (1) when a postoperative MR scan most accurately shows residual
      enhancing tumor; and (2) whether repeated doses of the contrast agent
      gadopentetate dimeglumine (Gd-DTPA) were well tolerated. PATIENTS AND METHODS:
      Seventeen patients with malignant glioma underwent tumor resection; four (24%)
      had nonenhancing tumors preoperatively. Serial MR scans were performed on
      postoperative days 1, 3, 5, 7, 14, and 21 and were analyzed qualitatively and
      quantitatively. The evolution of enhancement and subacute hemorrhage were
      described and measured. A uniform schedule of postoperative dexamethasone
      administration was used in all but four patients (24%) (each required higher
      doses to maintain neurologic function). RESULTS: Nontumoral, marginal (i.e.,
      postsurgical) enhancement, potentially mimicking residual tumor, developed in
      eight patients (53%), including tumors that were nonenhancing preoperatively, and
      was maximal from days 5 to 14. Tumor enhancement was optimally visualized on
      postoperative days 3 to 5. Nine of 10 patients (90%) with gross residual
      enhancing tumor showed an increase of enhancing tumor size during the study.
      Methemoglobin was detected at some time in all patients (100%) and was usually
      minor, but in six (35%) it interfered with residual tumor assessment. The 97
      doses of Gd-DTPA, administered in 17 patients, were well tolerated. CONCLUSION:
      When accurate assessment of residual enhancing tumor is needed in patients with
      malignant glioma, an MR scan performed on postoperative days 3 to 5 should
      minimize the confounding effects of postsurgical enhancement and methemoglobin.
      The repeated administration of Gd-DTPA over several weeks is well tolerated.

PMID- 9164221
TI  - Dose-intensity of a four-drug chemotherapy regimen with or without recombinant
      human granulocyte-macrophage colony-stimulating factor in extensive-stage small
      cell lung cancer: a multicenter randomized phase III study.
AB  - PURPOSE AND METHODS: We investigated whether a high-dose chemotherapy regimen of
      cyclophosphamide 1,800 mg/m2, 4'-epidoxorubicin 60 mg/m2, etoposide 330 mg/m2,
      and cisplatin 120 mg/m2 given monthly for four cycles with recombinant human
      granulocyte-macrophage colony-stimulating factor (rhGM-CSF) support (5
      micrograms/kg daily for 10 days) could improve the survival of patients with
      extensive-stage small-cell lung cancer (SCLC) compared with a standard-dose
      regimen (cyclophosphamide 1,200 mg/m2, 4'-epidoxorubicin 40 mg/m2, etoposide 225
      mg/m2, and cisplatin 100 mg/m2) given monthly for six cycles. Planned cumulative
      doses of the drugs were the same in both treatment arms except for cisplatin
      (which was 80% in the higher-dose plus rhGM-CSF group). RESULTS: At the time of
      the preplanned interim analysis, 125 patients, 60 in the standard-dose group and
      65 in the higher-dose plus rhGM-CSF group, had entered the study; 116 were
      eligible, 55 in the standard-dose group and 61 in the higher-dose group. All
      patients were included in the analyses. The cumulative doses of each drug
      actually delivered were significantly higher in the standard-dose group. No
      difference in response rates was observed between the two groups. There were
      significantly greater hematologic toxicities, documented infections, and
      transfusions of RBCs and platelets in the higher-dose plus rhGM-CSF group.
      Patients in this group proved to have a shorter survival duration and a shorter
      time to relapse than patients in the standard-dose group (median overall
      survival: standard-dose, 10.8 months; higher-dose, 8.9 months; log-rank test with
      adjustment for prognostic variables, P = .0005; respective probabilities of
      relapse at 1 year, 77 +/- 0.6 and 96 +/- 2.2; log-rank test, P = .013).
      CONCLUSION: A 50% increase in dose-intensity for this four-drug regimen could not
      be achieved with GM-CSF due to excessive toxicity in patients with extensive
      stage SCLC.

PMID- 9164222
TI  - Topotecan, a new active drug in the second-line treatment of small-cell lung
      cancer: a phase II study in patients with refractory and sensitive disease. The
      European Organization for Research and Treatment of Cancer Early Clinical Studies
      Group and New Drug Development Office, and the Lung Cancer Cooperative Group.
AB  - PURPOSE: To assess activity and toxicity of topotecan in previously treated small
      cell lung cancer (SCLC) patients. PATIENTS AND METHODS: Patients with measurable
      SCLC, progressive after one first-line regimen, were eligible for the study. Two
      groups of patients were selected: (1) patients who failed first-line treatment <
      or = 3 months from chemotherapy discontinuation (refractory group); and (2)
      patients who responded to first-line treatment and progressed greater than 3
      months after chemotherapy discontinuation (sensitive group). Topotecan was
      administered as a 30-minute daily infusion at a dose of 1.5 mg/m2 for 5
      consecutive days, every 3 weeks. RESULTS: One hundred one patients were entered
      onto the study and 403 courses were administered. Ninety-two patients (47
      refractory and 45 sensitive) were eligible and assessable for response. Among
      refractory patients, there were two partial responses (PRs) and one complete
      response (CR), for an overall response rate of 6.4% (95% confidence interval
      [CI], 1.3% to 17.6%), whereas in the sensitive group, there were 11 PRs and six
      CRs, for an overall response rate of 37.8% (95% CI, 23.8% to 53.5%). Overall
      median duration of response was 7.6 months. Median survival was 5.4 months;
      median survival of refractory patients was 4.7 months, whereas that of sensitive
      patients was 6.9 months (P = .002). Median survival of responding patients was
      12.5 months. Toxicity was mainly hematologic. Leukopenia, although short-lived,
      was universal, with grade III and IV neutropenia occurring in 28% and 46.8% of
      cycles, respectively. Nonhematological toxicity was mild. Fatigue/malaise was
      reported in 39.3% of cycles and transient elevation of liver enzymes in 17%.
      CONCLUSION: Topotecan has significant activity in SCLC, particularly in patients
      sensitive to prior chemotherapy, with predictable and manageable toxicity. The
      incorporation of topotecan in combination chemotherapy regimens for future
      treatment of SCLC is warranted.

PMID- 9164223
TI  - Gemcitabine versus the combination of cisplatin and etoposide in patients with
      inoperable non-small-cell lung cancer in a phase II randomized study.
AB  - PURPOSE: A phase II randomized study was conducted to evaluate the efficacy and
      toxicity of gemcitabine (GEM) versus the combination of cisplatin and etoposide
      (EP) in Chinese patients with inoperable (stage III or IV) non-small-cell lung
      cancer (NSCLC). PATIENTS AND METHODS: From March 1995 to February 1996, 53
      patients were enrolled onto the study: 27 onto the GEM arm and 26 onto the EP
      arm. In the GEM arm, gemcitabine 1,250 mg/m2 was given as a 30-minute intravenous
      (i.v.) infusion on days 1, 8, and 15 of each 28-day cycle. In the EP arm,
      cisplatin 80 mg/m2 was given on day 1 and etoposide 80 mg/m2 was given on days 1,
      2, and 3 of each 28-day cycle. RESULTS: Twenty-six patients are assessable for
      treatment response on the GEM arm and 24 on the EP arm. Five patients (19.2%) on
      the GEM arm and five patients (20.8%) on the EP arm achieved a partial response
      (PR). No complete responses were attained on either treatment arm. All patients
      enrolled onto the study were eligible for toxicity assessment. The main
      toxicities were myelosuppression and vomiting, which included World Health
      Organization (WHO) grade 3 or 4 leukopenia (3.7%), thrombocytopenia (7.4%),
      anemia (7.4%), and nausea/vomiting (3.7%) on the GEM arm, and WHO grade 3 or 4
      leukopenia (30.8%), thrombocytopenia (7.7%), anemia (15.4%), and nausea/vomiting
      (34.6%) on the EP arm. The median survival time was 37 weeks on the GEM arm and
      48 weeks on the EP arm. CONCLUSION: Gemcitabine is a well-tolerated
      chemotherapeutic agent for NSCLC. The antitumor activity was promising, with a
      19.2% single-drug response rate, when compared with EP combination chemotherapy,
      which had a response rate of 20.8%. The safety profile is better than that of EP
      treatment.

PMID- 9164225
TI  - Phase I trial of dose-intense liposome-encapsulated doxorubicin in patients with
      advanced sarcoma.
AB  - PURPOSE: To define the maximum-tolerated dose (MTD) of liposome-encapsulated
      doxorubicin (LED) when used every 2 weeks with granulocyte colony-stimulating
      factor (G-CSF) in patients with advanced soft tissue sarcoma. PATIENTS AND
      METHODS: Doxorubicin encapsulated in egg phosphatidylcholine/cholesterol
      liposomes was given to patients with sarcoma in a disease-specific phase I trial.
      The initial dose was 75 mg/m2 with G-CSF 5 micrograms/kg. The MTD was defined as
      the highest dose that could be given every 2 weeks. RESULTS: Twenty-nine patients
      participated in this study. Major toxicities included myelosuppression, nausea
      and vomiting, fatigue, and mucositis. Eight patients were hospitalized for nadir
      fever. No cardiotoxicity was seen. The MTD was LED 105 mg/m2 with G-CSF 5
      micrograms/kg. LED 120 mg/m2 resulted in tolerable, albeit prominent, acute
      toxicity, but did not permit recycling of therapy on day 15. Among 26 patients
      with soft tissue sarcoma, 23 had measurable disease, of whom three achieved a
      partial response (13%; 95% confidence interval, 2% to 34%). CONCLUSION: LED can
      be administered every 2 weeks at a dose of 105 mg/m2 with G-CSF support, which
      provides a dose-intensity of 52.5 mg/m2/wk. To exceed this intensity, the dose of
      LED that would have to be administered every 3 weeks would be greater than 157.5
      mg/m2. A formal phase II trial is needed to estimate better the true response
      rate.

PMID- 9164224
TI  - Active specific immunotherapy of metastatic melanoma with an antiidiotype
      vaccine: a phase I/II trial of I-Mel-2 plus SAF-m.
AB  - PURPOSE: To determine the toxicity and immunologic activity of an antiidiotype
      melanoma vaccine that consists of monoclonal antibody I-Mel-2 (MELIMMUNE-2, IDEC
      Pharmaceuticals, La Jolla, CA) and an immunologic adjuvant SAF-m. PATIENTS AND
      METHODS: Twenty-six patients with metastatic melanoma, 17 of whom had previously
      received chemotherapy, were given 2 mg of I-Mel-2 and either 100 micrograms (n =
      6) or 250 micrograms (n = 20) of SAF-m. Antiidiotype vaccine was given
      intramuscularly (IM) biweekly for 4 weeks, and then bimonthly until disease
      progression. Human antimurine antibodies (HAMA), anti-I-Mel-2 antibodies, and
      specific antibody (Ab)3 against the melanoma epitope mimicked by the vaccine were
      titrated before treatment, biweekly from weeks 4 to 12, and every 4 to 8 weeks
      thereafter. Computed tomographic (CT) scans of the chest, abdomen, and pelvis and
      magnetic resonance imaging (MRI) of the brain were obtained before and bimonthly
      during treatment to evaluate responses. RESULTS: Elevated titers of human
      antimouse antibodies and anti-I-Mel-2 antibodies were associated with clinical
      antitumor effect (P = .02 and P = .05, respectively). Ab3 was absent in most
      patients, but was found in the best clinical responder. Fever,
      myalgias/arthralgias, fatigue, nausea, and headaches were the most common
      toxicities. Grade III myalgias/arthralgias and headaches required dose reduction
      of SAF-m in eight patients at the 250-microgram dose. No treatment-related death
      occurred. Six patients had an antitumor effect: one complete response in liver
      and lung, two minor responses, and three stable disease. The patient with a
      complete response has survived nearly 5 years. CONCLUSION: I-Mel-2 antiidiotype
      vaccine was safe, tolerated best at the 100-microgram dose of SAF-m, and had
      immunologic and clinical activity.

PMID- 9164226
TI  - Clinical and pharmacokinetic study of oral etoposide in patients with AIDS
      related Kaposi's sarcoma with no prior exposure to cytotoxic therapy.
AB  - PURPOSE: In this phase II and pharmacokinetic study, chronic, low-dose, oral
      etoposide was evaluated for its efficacy in patients with AIDS-related Kaposi's
      sarcoma who were not previously exposed to cytotoxic therapy. PATIENTS AND
      METHODS: Of 28 patients accrued for the study, 25 were assessable for toxicity
      and response. Twenty-four patients were male (homosexual or bisexual cases) and
      one patient was female (partner of a bisexual male). All patients were human
      immunodeficiency virus (HIV)-positive, New York University (NYU) disease stage
      IIB to IVB, and most exhibiting skin and lymph node and/or visceral disease.
      Median age was 33 years (range, 21 to 50), and median World Health Organization
      (WHO) performance status was 2 (range, 0 to 3). The patients received a mean
      number of six treatment courses (range, four to 27). Prior therapy included
      local/regional irradiation, immunotherapy (interferon-alpha), local resection,
      and/or cryotherapy. No prior cytotoxic therapy was allowed. Etoposide was
      administered at a schedule of 25 mg/m2 orally, twice a day for 7 days, every 2
      weeks. Plasma concentrations of the drug were measured in six patients by a high
      performance liquid chromatography (HPLC) method, after chloroform extraction
      using teniposide as internal standard. RESULTS: The overall response rate was 32%
      (two complete and six partial responses), and the median progression-free
      survival was 8 weeks (range, 4 to 27). Five patients (20%) had stable disease,
      while 12 cases (48%) did not respond. Patients without a history of opportunistic
      infections seemed to respond better. The regimen was well tolerated. The main
      toxic effects consisted of mild to moderate nausea and vomiting in approximately
      half of the cases, and WHO grodes 3 to 4 leukopenia and thrombocytopenia in eight
      of 25 (36%) and five of 25 (20%) of cases, respectively. However, only two
      patients had to discontinue treatment because of prolonged and severe
      neutropenia. No toxic deaths were documented. The pharmacokinetic analyses
      revealed the achievement of potentially therapeutic and lowly myelosuppressive
      plasma etoposide concentrations (2.1 micrograms/mL; range, 1.3 to 2.6) for a
      significant period of time, ie, for approximately 4.6 hours postdosing.
      CONCLUSION: At the schedule applied, etoposide shows significant objective
      antitumor activity in advanced AIDS-related Kaposi's sarcoma, and induces
      acceptable clinical toxicity. This apparent efficacy of the regimen could be a
      result of the prolonged maintenance of cytotoxic plasma concentrations of
      etoposide during each treatment course, and the absence of toxic peak levels of
      the drug. These results, together with the appreciable bioavailability of oral
      etoposide, make the regimen feasible for outpatient treatment of patients with
      advanced AIDS-related Kaposi's sarcoma. Further studies using the above-mentioned
      approach are warranted.

PMID- 9164227
TI  - Carboxypeptidase-G2, thymidine, and leucovorin rescue in cancer patients with
      methotrexate-induced renal dysfunction.
AB  - PURPOSE: Methotrexate nephrotoxicity can lead to delayed methotrexate elimination
      and the development of life-threatening toxicity, which may not be preventable
      with the standard rescue agent leucovorin. In preclinical studies, we previously
      demonstrated that carboxypetidase-G2 (CPDG2) rapidly hydrolyzes methotrexate to
      nontoxic metabolites. A protocol for the compassionate use of CPDG2 in patients
      who develop nephrotoxicity while receiving high-dose methotrexate was therefore
      developed. The pharmacologic and clinical outcome of CPDG2 rescue administered
      with thymidine and leucovorin in 20 patients is presented here. METHODS: Patients
      with high-dose methotrexate-induced renal dysfunction received one to three doses
      of CPDG2, 50 U/kg body weight intravenously (i.v.), thymidine 8 g/m2/d by
      continuous i.v. infusion, and standard pharmacokinetically guided leucovorin
      rescue. Plasma concentrations of methotrexate and its inactive metabolite 4-deoxy
      4-amino-N10-methylpteroic acid (DAMPA) were measured before and after CPDG2 using
      high-pressure liquid chromatography (HPLC). Tolerance of CPDG2 and thymidine,
      development of methotrexate toxicities, and recovery of renal function were
      monitored. RESULTS: Twenty patients who received high-dose methotrexate for
      osteosarcoma (n = 11), lymphoid cancers (n = 8), and gastric cancer (n = 1)
      developed nephrotoxicity (median serum creatinine, 3.2 mg/dL) and elevated plasma
      methotrexate concentrations (median, 201 mumol/L at hour 46). CPDG2 and thymidine
      rescue was well tolerated and resulted in a rapid 95.6% to 99.6% reduction in the
      plasma methotrexate concentration. Methotrexate-related toxicity was mild to
      moderate. Serum creatinine returned to normal values at a median of 22 days.
      CONCLUSION: CPDG2, thymidine, and leucovorin rescue was highly effective in 20
      patients at high risk for developing life-threatening methotrexate toxicity after
      the onset of methotrexate-induced nephrotoxicity and delayed methotrexate
      excretion.

PMID- 9164229
TI  - Hereditary cancer risk notification and testing: how interested is the general
      population?
AB  - PURPOSE: Great interest in predictive testing for hereditary cancer syndromes has
      been reported. Prior research has focused on testing for specific hereditary
      syndromes and/or among individuals at high risk for positive carrier status.
      Given anticipated expansion of both the range of hereditary syndromes for which
      testing will be available, as well as the clinical settings in which testing will
      occur, assessment of interest in hereditary cancer risk testing and notification
      in the general public is warranted. METHODS: As part of an annual statewide
      telephone survey, adults' (N = 654) interest in hereditary cancer risk testing
      and notification was assessed. RESULTS: Interest in both risk testing (82%) and
      risk notification (87%) was high. Logistic regression analyses indicated that
      disinterest in risk notification was associated with female sex, performance of
      fewer health protective behaviors, and better perceptions of personal health.
      Disinterest in risk testing was associated with these same variables as well as
      older age, less concern over developing cancer, and a more extensive history of
      cancer in first degree relatives. CONCLUSION: In the absence of risk-reducing
      behaviors with demonstrable efficacy, hereditary risk testing programs may have
      difficulty attracting the interest of those at greatest risk for carrier status.
      In contrast, many individuals at low risk for positive carrier status might seek
      testing, perhaps as a means of seeking reassurance regarding their low hereditary
      risk.

PMID- 9164228
TI  - Prevention of acute emesis in cancer patients following high-dose cisplatin with
      the combination of oral dolasetron and dexamethasone.
AB  - PURPOSE: Dolasetron is a 5-HT3 antagonist antiemetic with active oral and
      intravenous formulations. The effects of this class are enhanced when combined
      with dexamethasone. This study tested the ability of the combination of oral
      dolasetron 200 mg and oral dexamethasone 20 mg to prevent acute emesis in cancer
      patients receiving initial cisplatin at doses > or = 70 mg/m2. Additionally,
      patients were randomly assigned to receive a second dosage of the regimen 16
      hours later to improve control of acute symptoms. PATIENTS AND METHODS: A total
      of 75 patients were entered, with 38 randomized to the two-dose regimen. Thirty
      five percent were women and 77% had lung cancer. RESULTS: Overall, the regimen
      prevented acute vomiting in 76% (95% confidence interval, 65% to 85%), including
      74% of 35 patients who received cisplatin at doses > or = 100 mg/m2. There was no
      observed difference in emesis prevention between the one-dose (76%) and two-dose
      (76%) regimens (95% confidence interval for the difference, -20% to 19%). The
      median time to the onset of emesis was 19 hours for the one-dose regimen and 17
      hours for the two-dose regimen in those patients with emesis. Headache occurred
      in 11% who received one dose and 16% who received two doses. CONCLUSION: The
      combination of oral dolasetron 200 mg and dexamethasone 20 mg given only once
      prevented acute emesis in 76% of patients who received cisplatin > or = 70 mg/m2.
      Administration of a second dose of the regimen did not improve the observed
      prevention rate or delay the time to emesis. This one-dose oral regimen has
      comparable or better effectiveness than reported results of intravenous
      combination regimens in preventing cisplatin-induced vomiting and merits further
      study and use.

PMID- 9164230
TI  - Recommended breast cancer surveillance guidelines. American Society of Clinical
      Oncology.
AB  - OBJECTIVE: To determine an effective, evidence-based postoperative surveillance
      strategy for the detection and treatment of recurrent breast cancer. Tests are
      recommended only if they have an impact on the outcomes specified by the American
      Society of Clinical Oncology (ASCO) for clinical practice guidelines. POTENTIAL
      INTERVENTION: All tests described in the literature for postoperative monitoring
      were considered. In addition, the data were critically evaluated to determine the
      optimal frequency of monitoring. OUTCOME: Outcomes of interest include overall
      and disease-free survival, quality of life, toxicity reduction, and secondarily
      cost-effectiveness. EVIDENCE: A search was performed to determine all relevant
      articles published over the past 20 years on the efficacy of surveillance testing
      for breast cancer recurrence. These publications comprised both retrospective and
      prospective studies. VALUES: Levels of evidence and guideline grades were rated
      by a standard process. More weight was given to studies that tested a hypothesis
      that directly related testing to one of the primary outcomes in a randomized
      design. BENEFITS/HARMS/COSTS: The possible consequences of false-positive and
      negative tests were considered in evaluating a preference for one of two tests
      that provided similar information. Cost alone was not a determining factor.
      RECOMMENDATIONS: The attached guidelines summarize the recommendations of the
      ASCO breast cancer expert panel (see Table 1 for a summary of guidelines and
      corresponding levels of evidence and grades of recommendation). Data are
      sufficient to recommend monthly breast self-examination, annual mammography of
      the preserved and contralateral breast, and a careful history and physical
      examination every 3 to 6 months for 3 years, then every 6 to 12 months for 2
      years, then annually. Data are not sufficient to recommend routine bone scans,
      chest radiographs, hematologic blood counts, tumor markers (CEA, CA15-5), liver
      ultrasonograms, or computed axial tomographic scans. VALIDATION: The
      recommendations of the breast cancer expert panel were evaluated by the ASCO
      Health Services Research Committee reviewers and by the ASCO Board of Directors.

PMID- 9164231
TI  - Resource document for curriculum development in cancer genetics education.
      American Society of Clinical Oncology.
AB  - PURPOSE: The rapid growth in the use of genetic testing for heritable cancers and
      other diseases has led to the establishment of many committees to assess the
      status and future implications of such testing. The American Society of Clinical
      Oncology (ASCO) published a statement on genetic testing for cancer
      susceptibility in May 1996. In that statement, ASCO recognized the need for a
      major initiative to develop courses and other educational materials for ASCO
      members and other health care professionals that were pertinent to cancer
      genetics and the role of cancer predisposition testing in clinical oncology.
      These curriculum guidelines represent an effort to promote formal instruction on
      the assessment and management of familial cancer risks in training programs and
      continuing education courses. DESIGN AND RESULTS: An Ad hoc Task Force was
      created from the ASCO membership and other professional organizations. Goals of
      ASCO's cancer genetics education initiative, curriculum guidelines, and plans for
      implementation of the curriculum have been developed. To gain understanding and
      competency in cancer genetics and cancer predisposition testing, the curriculum
      emphasizes formal instruction in: (1) basic concepts and principles of genetics;
      (2) an understanding of the role of genetics in the etiology, diagnosis, and
      management of different malignancies; (3) an understanding of the ethical, legal,
      and social issues that surround predisposition testing; and (4) long-term
      management plans for individuals at high risk for cancer. This document is broad
      in scope and applicable to all types of malignancies. It should be considered as
      the framework around which cancer genetics education is developed. It is expected
      that implementation of training activities over the next few years will allow
      ASCO to fulfill its obligations to the membership. CONCLUSION: This curriculum
      should prove a valuable guide to those who wish further education on cancer
      genetics and the appropriate use of cancer predisposition testing.

PMID- 9164232
TI  - Diagnosis in Oncology. Leukemia cutis.

PMID- 9164233
TI  - Survival benefit in melanoma.

PMID- 9164234
TI  - More is better but ... how is best: are milligrams over hours better than grams
      over minutes? The case of gemcitabine.

PMID- 9164235
TI  - Isolated limb perfusion with high-dose tumor necrosis factor-alpha in combination
      with interferon-gamma and melphalan for nonresectable extremity soft tissue
      sarcomas: a multicenter trial.

PMID- 9164236
TI  - Tumor marker guidelines.

PMID- 9164237
TI  - Sinus histiocytosis with massive lymphadenopathy: complete response to low-dose
      interferon-alpha.

PMID- 9164238
TI  - An overview of recent developments in avian lipoprotein metabolism.

PMID- 9164239
TI  - Evolution of processes and regulators of lipoprotein synthesis: from birds to
      mammals.
AB  - Mammalian lipoproteins are synthesized in the liver and secreted into the blood
      plasma where they are targeted to specific tissues. Through specific cell surface
      receptors, hepatic lipoproteins are taken up and their lipid contents are then
      used for anabolic and energy requirements. Because of the well-established role
      that plasma lipoproteins play as risk factors for the development of
      cardiovascular disease, a great amount of attention has been directed toward
      understanding their metabolism and biosynthesis. The major focus of this report
      is to review the evolution of gene products that are essential in regulating,
      synthesizing, assembling and secreting the lipid and protein components of
      lipoproteins. Using the primordial vitellogenin lipoprotein system as the
      paradigm, I show how metabolic signals derived from the sterol biosynthetic
      pathway provide a coordinate regulation of genes necessary to assemble and
      secrete mammalian apolipoprotein B-containing lipoproteins. In lower species,
      estrogen induces the expression of genes required for both vitellogenin synthesis
      and its tissue targeting (the vitellogenin receptor). This coordinate induction
      provides lipid to the ovaries for egg development. In mammals, a sterol-derived
      metabolic signal regulates the expression of genes required for lipoprotein
      synthesis and for the LDL receptor. The signal is not sex linked, providing an
      adaptive advantage to changes in nutritional status.

PMID- 9164240
TI  - Low density lipoprotein receptor gene family members mediate yolk deposition.
AB  - Yolk represents the last growth stage of a single cell, the oocyte, which
      contains, besides bona fide cytoplasm, endocytosed serum-derived lipoproteins and
      minor components essential for normal embryo development. Transport of bulk
      lipoproteins, micronutrients, and morphogens to oocytes in parallel with
      maintenance of somatic homeostasis is achieved by ligand targeting via cell
      specific expression of receptors and subtle differences in ligand structure.
      Lipoprotein metabolism is the prime example of these regulatory principles, in
      which receptors belonging to the low density lipoprotein receptor gene family
      play key roles. Here, we present the laying hen's features that make it an
      attractive model system to dissect macromolecular transport processes at the
      molecular level. In addition to the characterization of a family of yolk
      precursor receptors, studies on systemic vs. oocyte-directed transport have
      uncovered new aspects of the biological rationale for simultaneous expression of
      closely related genes in a single organism.

PMID- 9164241
TI  - Lipoprotein metabolism and fattening in poultry.
AB  - Because de novo fatty acid synthesis in birds takes place mainly in the liver,
      adipose tissue growth and subsequent fattening depend on the availability of
      plasma triglycerides, which are transported as components of lipoproteins. In
      growing birds, VLDL is the major transporter of triglycerides, and attempts to
      reduce excessive fatness in poultry have involved the control of VLDL metabolism.
      Lean and fat lines of chickens have been selected on the basis of either their
      abdominal fat content or plasma VLDL concentration. In both cases, hepatic
      lipogenesis or LPL activity in adipose tissue did not differ between lean and fat
      lines, and therefore they did not appear to be limiting factors of susceptibility
      to fattening. In contrast, hepatic secretion and plasma concentration of VLDL
      were always higher in fat chickens than in lean chickens. Thus, current methods
      of selection of broilers against excessive fatness are based on this direct
      relationship between plasma VLDL and adiposity. When hepatic lipogenesis exceeds
      the capacity of VLDL secretion, triglycerides accumulate in the liver, causing
      steatosis. Although fatty liver is associated with reduced egg production and
      increased mortality in laying hens, hepatic steatosis in overfed ducks and geese
      is of positive economic value, serving as the basis for "foie-gras" production.
      The balance between synthesis and secretion of VLDL is therefore the key point
      that regulates hepatic and extrahepatic fattening in poultry.

PMID- 9164242
TI  - Analysis of forage fiber and cell walls in ruminant nutrition.
AB  - Analysis of the fiber or cell wall present in forages is of major concern in
      ruminant nutrition because diets often contain large amounts of forage, and the
      fiber fraction affects both feed intake and animal performance. Traditional
      extractive, gravimetric methods such as crude fiber and neutral detergent fiber
      recover variable amounts of the plant cell wall, but they remain popular because
      of their ease of use and the large feed data bases available for these methods.
      More intensive chemical methods utilizing chromatography and spectrometric
      analysis provide greater detail on cell wall composition and structure, but they
      have been used little in ruminant nutrition. Lignin analysis has remained
      problematic because no definitive reference method exists. Recently attention has
      focused on the measurement of lignin composition and cell wall phenolic acids;
      however, these methods have yet to be widely adopted in ruminant nutrition. The
      detergent fiber methods have been semi-automated to increase sample handling
      capacity. Near-infrared spectroscopy is routinely used for prediction of fiber
      concentration in forages and has greatly increased the ease of obtaining fiber
      analysis of forage samples. Widespread adoption in ruminant nutrition of the more
      sophisticated methods of cell wall analysis is unlikely to occur until these
      methods can be demonstrated to improve diet formulation and prediction of animal
      performance.

PMID- 9164243
TI  - Plant limitations to fiber digestion and utilization.
AB  - Energy availability from forages is limited by fiber concentration because fiber
      is slowly and incompletely digested, whereas cell solubles are almost completely
      digested. Thus, the proportion of fiber to cell solubles is a major determinant
      of energy availability in forages. Grasses normally have more fiber than legumes,
      especially in leaves. Grass fiber is more digestible than that of legumes, but
      that of legumes digests at a faster rate. Ruminants digest 40-50% of legume fiber
      and 60-70% of grass fiber. Some fiber cannot be digested no matter how long it
      remains in the rumen. Lignin is thought to interfere with microbial degradation
      of fiber polysaccharides by acting as a physical barrier and by being cross
      linked to polysaccharides by ferulate bridges. In addition to the effects of
      lignin, physical and structural barriers may limit fiber digestibility. Because
      the middle lamella and primary wall of thick-walled cells are so highly
      lignified, many cells can be digested only from the interior of the cell. For
      many cells, access to cell interiors is limited because of large particle sizes.
      Forage digestibility could be improved by reducing the amount of lignified cells
      or by developing improved cultivars so that lignified cells are more digestible.

PMID- 9164244
TI  - Microbial and animal limitations to fiber digestion and utilization.
AB  - The ruminal microbial populations attack, degrade and ferment structural
      carbohydrates in forage cell walls and thereby provide volatile fatty acids and
      protein to the host animal. Microbial colonization of fiber is quite rapid;
      however, the rate and extent to which fiber is degraded is determined to a
      considerable degree by factors such as microbial accessibility to substrate,
      physical and chemical nature of the forage and kinetics of ruminal digestion. The
      physical and chemical nature of forages can present a barrier to their complete
      digestion in the rumen, especially the association of lignin with polysaccharide
      constituents. Adhesin proteins allow bacteria with cell-bound enzymes to come
      into intimate contact with their substrates, ensuring that the degradation
      products are preferentially available. Research on various fibrolytic enzymes and
      cellulose binding domains may allow for the transfer of novel genetic material to
      bacteria for enhancing the hydrolysis of plant cell walls. Fungi may also play an
      important synergistic role in the ruminal digestion of forages by physically
      disrupting the lignified stem tissue. This allows the ruminal microbes greater
      access to the plant stem and the digestible portions of the plant. New
      developments in fiber utilization by ruminants are currently under investigation
      and include genetic manipulation of ruminal bacteria, chemical and biological
      treatments of forages, and manipulation of dietary inputs and feeding management.

PMID- 9164246
TI  - Effects of diet on urinary bladder carcinogenesis and cancer prevention.
AB  - Urine plays a major role in bladder carcinogenesis, acting as a transport
      mechanism for carcinogens, containing several growth factors stimulating cell
      proliferation, and indirectly affecting chemicals by alterations in
      concentrations of normal urinary components such as electrolytes, water and
      proteins. These latter effects are greatly modified by diet composition and
      consumption and also by water consumption. Several examples of these effects are
      presented.

PMID- 9164247
TI  - Importance of sphingolipids and inhibitors of sphingolipid metabolism as
      components of animal diets.
AB  - Sphingolipids are highly bioactive compounds that participate in the regulation
      of cell growth, differentiation, diverse cell functions, and apoptosis. They are
      present in both plant and animal foods in appreciable amounts, but little is
      known about their nutritional significance. Recent studies have shown that
      feeding sphingomyelin to female CF1 mice treated with a colon carcinogen (1,2
      dimethylhydrazine) reduced the number of aberrant colonic crypt foci; longer-term
      feeding also affected the appearance of colonic adenocarcinomas. Therefore,
      dietary sphingolipids should be considered in studies of the relationships
      between diet and cancer. Sphingolipids have also surfaced as important factors in
      understanding the mechanism of action of a recently discovered family of
      mycotoxins, termed fumonisins. Fumonisins are produced by fungi commonly found on
      maize and a few related foods, and their consumption can result in equine
      leukoencephalomalacia, porcine pulmonary edema and a number of other diseases of
      veterinary animals and, perhaps, humans. A cellular target of fumonisins is the
      enzyme ceramide synthase, and disruption of sphingolipid metabolism by fumonisins
      has been established by studies with both cells in culture and animals that have
      consumed these toxic mycotoxins. These findings underscore the ways in which
      sphingolipids and agents that affect sphingolipid utilization should be given
      consideration in selecting animal diets for nutritional and toxicological
      studies.

PMID- 9164248
TI  - Dietary nucleotides: effects on cell proliferation following partial hepatectomy
      in rats fed NIH-31, AIN-76A, or folate/methyl-deficient diets.
AB  - The requirement of a number of tissues for dietary nucleotides could explain some
      of the differences observed in animals fed natural ingredient diets vs. those fed
      purified diets lacking a source of dietary nucleotides. Lack of dietary
      nucleotides is exacerbated in animals fed folate- or methyl-deficient
      semipurified diets, in which both salvage and folate-dependent de novo synthetic
      pathways are diminished. We examined hepatocyte proliferation following partial
      hepatectomy in weanling male Fischer-344 rats fed natural ingredient NIH-31 diet,
      nucleotide-free purified AIN-76A diet or a basal diet similar to AIN-76A but
      deficient in the methyl donors folate, choline and methionine. Additional groups
      were fed AIN-76A or folate/methyl-deficient diets supplemented with 0.25% yeast
      RNA. Compared with NIH-31, AIN-76A increased dUMP/dTTP ratios, reduced the
      mitotic index (MI) and increased the ratio of proliferating cell index (PCI) to
      mitotic cells, an indication that hepatocytes were delayed in S-phase. Addition
      of yeast RNA to AIN-76A reversed (by approximately 50%) the effects of AIN-76A on
      dUMP/dTTP and cell proliferation. A folate/methyl-deficient diet also produced an
      increased dUMP/dTTP ratio and markedly reduced the MI, increasing the PCI/MI,
      which suggested even further delay of cells in S-phase. Addition of yeast RNA to
      the folate/methyl-deficient diet was effective in significantly reversing the
      effects of folate/methyl deficiency.

PMID- 9164249
TI  - Components of the AIN-93 diets as improvements in the AIN-76A diet.
AB  - The AIN-93 rodent diets were formulated to substitute for the previous version
      (AIN-76A) and to improve the performance of animals that consume them. They are
      called AIN-93G, formulated for growth, and AIN-93M, for maintenance. Major
      changes included substituting cornstarch for sucrose and soybean oil for corn oil
      and increasing the amount in order to supply both essential fatty acids (linoleic
      and linolenic). L-Cystine was substituted for DL-methionine to supplement the
      casein component. The mineral mix was reformulated to lower the amounts of
      phosphorus, manganese and chromium, to increase the amount of selenium, and to
      add molybdenum, silicon, fluoride, nickel, boron, lithium and vanadium. The
      amounts of vitamins E, K-1 and B-12 were increased over those in the AIN-76A
      vitamin mix. The AIN-93G diet contains 200 g of casein and 70 g of soybean oil/kg
      diet. The maintenance diet (AIN-93M) contains 140 g of casein and 40 g of soybean
      oil/kg diet. The 1993 diets have a better balance of essential nutrients than the
      1976 diet and are better choices for studies with laboratory rodents.

PMID- 9164250
TI  - New nonpurified diet (NTP-2000) for rodents in the National Toxicology Program's
      toxicology and carcinogenesis studies.
AB  - The NIH-07 open-formula nonpurified diet was the selected diet for rodents in the
      National Toxicology Program's toxicology and carcinogenesis studies from 1980 to
      1994. Protein and mineral concentrations of the NIH-07 diet may have increased
      some diet- and age-associated lesions such as nephropathy. A number of
      experimental nonpurified diets with lower protein and higher fat and fiber
      (approximately 15% protein, 7-8.5% fat, and 9-14% crude fiber) than the NIH-07
      diet were formulated and evaluated in Fischer 344 (F344) rats. Decreasing protein
      content of the diet decreased protein consumption by approximately 30% and
      decreased severity of nephropathy without affecting growth. Increased fat intake
      seemed to have decreased the incidence or severity of leukemia, a lethal neoplasm
      of F344 rats. Increasing fiber content without decreasing the caloric density
      lowered body weight gain and slowed growth of mammary tumors. Higher fat and/or
      fiber intake decreased the incidences of adrenal pheochromocytomas and medullary
      hyperplasia in male rats. Nonpurified diets with lower protein and higher fat and
      fiber concentrations than the NIH-07 diet decreased or delayed diet- and age
      associated lesions and increased survivals in 2-y studies. On the basis of these
      results, a new cereal-based nonpurified diet, designated as NTP-2000, was
      formulated with approximately 14.5% protein, approximately 8.2% fat,
      approximately 9.3% fiber and a calcium:phosphorus molar ratio of approximately
      1.3. The NTP-2000 diet was compared with the NIH-07 diet in a 13-wk study in F344
      rats. The NTP-2000 diet was adequate for growth, did not affect the hematological
      parameters and did not cause substantial changes in blood chemistry, serum enzyme
      or serum electrolyte values. The NTP-2000 diet decreased liver and kidney
      weights, prevented nephrocalcinosis and decreased the severity of diet- and
      possibly age-associated lesions.

PMID- 9164251
TI  - Some considerations for the development of diets for mature rodents used in long
      term investigations.
AB  - Nutritional requirements for mature rodents used in long-term investigations are
      virtually unknown. The limited knowledge of the dietary needs of mature rodents
      is due in part to overreliance on weanling animals fed an experimental diet for
      relatively short periods. Generalizations made from observations of weanling
      rodents are not appropriate for all ages. Dietary recommendations for rodents
      have been established, for the most part, by using the nutritional benchmark of
      maximal growth rate in animals fed ad libitum. Although this method provides
      valuable insight into the understanding of nutritional deficiency, it is less
      effective in determining nutrient requirements for mature animals used for the
      long term. The implication that maximal growth resulting from ad libitum feeding
      may not indicate the best dietary regimen in the long term is consistent with the
      observation that energy-restricted rodents live significantly longer and have
      lower incidence of disease that do their ad libitum-fed counterparts. These and
      other findings discussed in the review suggest that nutrient requirements
      established for young rodents may need re-evaluation to determine their
      applicability to the dietary recommendations for older animals used in long-term
      investigations.

PMID- 9164252
TI  - The effects of diet, overfeeding and moderate dietary restriction on Sprague
      Dawley rat survival, disease and toxicology.
AB  - Overfeeding by ad libitum (AL) food consumption is the most significant,
      uncontrolled variable affecting the outcome of the current rodent bioassay. The
      correlation of food consumption, the resultant adult body weight and the 2-y
      survival in Sprague-Dawley rats is highly significant. Feeding natural ingredient
      diets that varied in protein, fiber and metabolizable energy content did not
      improve low 2-y survival if Sprague-Dawley rats were allowed AL food consumption.
      Moderate dietary restriction (DR) of all diets tested significantly improved
      survival and delayed the onset of spontaneous degenerative disease (i.e.,
      nephropathy and cardiomyopathy) and diet-related tumors. By 2 y, moderate DR
      resulted in an incidence of spontaneous tumors similar to that seen with AL
      consumption; however, the tumors were more likely to be incidental and did not
      result in early mortality. There was a decreased age-adjusted incidence in
      pituitary and mammary gland tumors, but tumor volume and growth time were similar
      in the AL and DR groups, indicating a similar tumor progression with a delay in
      tumor onset. Moderate DR did not significantly alter drug-metabolizing enzyme
      activities or the toxicologic response to five pharmaceuticals tested at maximum
      tolerated doses (MTD). However, moderate DR did require higher doses of compounds
      to be given before classical MTD were produced with four pharmaceutical drug
      candidates. Toxicokinetic studies of two of these compounds demonstrated steady
      state systemic exposures that were equal or higher in moderate DR-fed rats. These
      and other data indicate that moderate DR is the most appropriate method of
      dietary control for rodent bioassays used to assess human safety of candidate
      pharmaceuticals.

PMID- 9164253
TI  - From Olympia to Atlanta: a cultural-historical perspective on diet and athletic
      training.
AB  - Greek and Roman writers described diet and training of Olympic athletes. Lucian
      (A.D. 120-ca. 180) described distance and speed work in runners; Galen (A.D. 131
      201) recommended ball-related exercises to train vision and the body;
      Philostratos (A.D. 170-249) suggested cross training by endurance running, weight
      training, and wrestling with animals. The ancient Greek training system, the
      tetrad (eta tau epsilon tau rho alpha sigma), was a four-day cycle with each day
      devoted to a different activity. Diogenes Laertius (died A.D. 222) wrote that
      Greek athletes trained on dried figs, moist cheese and wheat; then the pattern
      changed and focused on meat. Epictetus (2nd century A.D.) wrote that Olympic
      victors avoided desserts and cold water and took wine sparingly. Philostratos
      deprecated athletic diet in his era, a pattern based on white bread sprinkled
      with poppy seeds, fish and pork. Americans at the XIth Olympiad in Berlin (1936)
      consumed beefsteak with average daily intake of 125 grams of butter or cotton
      oil, three eggs, custard for dessert and 1.5 L of milk. The American pattern at
      Berlin was characterized by ad libitum intake of white bread, dinner rolls, fresh
      vegetables and salads. At Atlanta, more than 5 million meals will be served
      during the Olympic festival. The highly varied menu will include fresh vegetables
      and dips; fruits, cheeses and breads; salads; pasta, rice and fruit salads;
      soups; meat and seafood entrees; hot vegetables; desserts; and beverages.
      American Southern specialties will be served.

PMID- 9164254
TI  - Search for the competitive edge: a history of dietary fads and supplements.
AB  - The premise and promise of ergogenic aid use is rooted in antiquity and is based
      upon superstition and ritualistic behavior of athletes who perceive that past
      performances were predicated upon unique dietary constituents or dietary
      manipulation. Accounts from ancient times recommended that athletes and soldiers
      preparing for battle consume specific animal parts to confer agility, speed or
      strength associated with that animal. Scientific understanding of the chemical
      and physiological nature of muscular work in the early 20th century was followed
      by ergogenic aid use by athletes and rationalized as "scientific" justification.
      Ergogenic aids such as alkaline salts, caffeine, carbohydrate and protein have
      been used by athletes with variable success. As nutritionists and exercise
      physiologists discovered and perfected the scientific understanding of metabolic
      reactions, athletes in turn experimented with the amount, form and timing of
      administration in the search for optimal performance. Anabolic steroids and blood
      doping enhance athletic performance, but health risks, ethics and sportsmanship
      contravene their use. Popularity and use of ergogenic aids often have preceded
      scientific substantiation of claims. Current products such as protein isolates
      and antioxidant nutrients commonly are used by athletes, and many ergogenic aids
      available today differ little from those used long ago.

PMID- 9164255
TI  - Diets of elite athletes: has the discipline of sports nutrition made an impact?
AB  - Although numerous descriptions exist of special diets and particular foods used
      by Greek athletes as early as 580 B.C., survey data on diets of Olympians of the
      modern era are virtually nonexistent. A survey in Helsinki in 1952 reported the
      diets of Olympic athletes to be high energy, high fat, and high protein. The 1952
      Olympians reportedly consumed an average daily energy intake of 18,841 kJ, with
      40% of energy coming from carbohydrate, 20% from protein, and 40% from fat. More
      recent data on elite level athletes reveal wide variation in dietary intake. For
      example, energy intakes of athletes from four countries ranged from 7699 to
      24,845 kJ. Group percentages of energy from carbohydrate, protein, and fat ranged
      from 33 to 57%, 12 to 26%, and 29 to 49%, respectively. Comparing dietary intake
      data of athletes on an absolute basis, however, is primarily a comparison of body
      size. When the protein and carbohydrate intakes of elite athletes are calculated
      as grams per kilogram body weight, the range for protein is 1.0-4.3 g/kg body wt
      for protein and 3.5-6.9 g/kg body wt for carbohydrate. Interestingly, variations
      in carbohydrate intake diminished while protein intake varied by country.
      Although some data on diets of Olympians exist, the most remarkable finding when
      reviewing the literature is the paucity of data. The discipline of sports
      nutrition has arguably had a positive effect on sports performance. However, many
      unanswered questions remain and great strides remain to be made.

PMID- 9164256
TI  - Sports medicine: a century of progress.
AB  - According to the international Olympic Committee, it is the responsibility of the
      sports medicine profession to care for the health and welfare of Olympic
      athletes, treat and prevent injuries, conduct medical examinations, evaluate
      performance capacity, provide nutritional advice, prescribe and supervise
      training programs, and to monitor substance use. Implicit in these functions is
      to assist Olympic athletes in achieving the objectives of the Olympic Motto
      (Citius, Altius, Fortius), which is to become faster, higher, and stronger.
      During the past Olympiads, athletic performance has increased, as indicated by
      times for the men's marathon (-28%) or by the distance covered in the women's
      javelin throw (+80%). However, the fulfillment of these responsibilities was a
      slow and protracted process, as demonstrated by the facts that medical
      examinations were not required until 1920, that 28 years elapsed before an
      official team physician was appointed, and that women had to wait until 1984
      before sanction was given to compete in the marathon race. Doping was not defined
      until 1964, and monitoring of substance abuse did not materialize until after
      1972. Although individuals have prepared for athletic competition since the
      ancient Olympics, the scientific foundations for various training prescriptions
      were not firmly established until the 1960s and 1970s. It was speculated that
      performance records will continue to improve in the next century because more
      scientific sports medicine information would be available and because such
      information would be better disseminated to athletes.

PMID- 9164257
TI  - Gold medal roundtable: athlete presentations, audience questions, and summary
      statements.

PMID- 9164258
TI  - Nutritional factors required for alcoholic liver disease in rats.
AB  - Decades ago it was suggested that nutritional factors are important in the
      development of alcoholic liver disease (ALD). However, several models of
      experimental alcoholism considered that the diets fed to animals were
      nutritionally adequate, complete and balanced. Therefore, a concept prevailed
      that the effects observed were due to alcohol per se and that they occurred
      despite a nutritionally adequate status in the animal. Examination of various
      models revealed that animals were malnourished because they ingested reduced
      levels of macro- and micronutrients. Furthermore, they consumed only small
      amounts of carbohydrate and a high level of unsaturated fat for long periods
      during the development of ALD. Alcoholic rats show many effects of inadequate
      nutritional status, such as a slow growth, depressed levels of liver glycogen and
      pancreatic amylase, enhanced protein degradation and circulating levels of
      branched-chain amino acids, and increased levels of enzymes involved in
      gluconeogenesis and alterations in the activities of enzymes related to the
      metabolism of carbohydrate as compared with controls. Chronic consumption of
      alcohol did not result in fatty liver, high blood alcohol concentration (BAC) or
      other observed effects when intake of energy, carbohydrate and other nutrients
      was increased. Furthermore, pre-existing effects of alcohol consumption, such as
      fatty liver, BAC and delayed gastric emptying, were reversed in rats receiving
      increased energy and carbohydrate intakes while continuing alcohol ingestion.
      Thus, nutritional status of the animal determines the production or prevention of
      ALD or other effects that were considered to be due to alcohol alone.

PMID- 9164259
TI  - Spin trapping studies of alcohol-initiated radicals in rat liver: influence of
      dietary fat.
AB  - We conducted spin trapping experiments to test the effects of acute and chronic
      alcohol consumption in livers from rats that had been fed either high fat (35% of
      energy) or low fat (12% of energy) liquid diets. Rats were anesthetized with
      isoflurane, the spin trapping agent POBN [alpha-(4-pyridyl-1-oxide)-N-t
      butylnitrone] was administered by intravenous injection, and bile samples were
      collected for electron paramagnetic resonance (EPR) analyses. Two different types
      of EPR spectra were observed in bile from the animals in these studies. One set
      of spectral lines was from the 1-hydroxyethyl radical adduct of POBN, which was
      conclusively identified by injecting the rats with [1-13C]ethanol. The EPR
      signals of a second type of radical adduct in bile could be observed both before
      and after acute administration of ethanol. Although the radical(s) responsible
      for this second series of signals could not be conclusively identified, it is
      likely that lipid radicals were formed under these conditions and trapped by
      POBN. For both types of radical adducts, the most intense EPR signals were
      observed in rats that had been fed alcohol in combination with a high fat diet
      for 2 wk before the experiments. These results confirm and extend previous data
      indicating that high levels of dietary fat enhance alcohol-associated free
      radical formation in the liver.

PMID- 9164260
TI  - Role of Kupffer cells, endotoxin and free radicals in hepatotoxicity due to
      prolonged alcohol consumption: studies in female and male rats.
AB  - Alcohol ingestion results in increases in the release of endotoxin from gut
      bacteria or membrane permeability of the gut to endotoxin, or both. Female rats
      are more sensitive to these changes. Elevated levels of endotoxin activate
      Kupffer cells to release substances such as eicosanoids, tumor necrosis factor
      alpha and free radicals. Prostaglandins increase oxygen uptake and most likely
      are responsible for the hypermetabolic state in the liver. The increase in oxygen
      demand leads to hypoxia in the liver, and on reperfusion, alpha-hydroxyethyl free
      radicals are formed that lead to tissue damage in oxygen-poor pericentral regions
      of the liver lobule.

PMID- 9164261
TI  - Lipid peroxidation, CYP2E1 and arachidonic acid metabolism in alcoholic liver
      disease in rats.
AB  - The role of cytochrome P450 metabolism of fatty acids and lipid peroxidation in
      the alterations of the fatty acid composition of the liver and liver pathology
      was investigated. The CYP2E1 inhibitors partially prevented CYP2E1 induction by
      ethanol and completely blocked lipid peroxidation. However, the liver pathology
      induced by ethanol was only partially prevented as was the decrease in
      arachidonic acid in total liver lipid, triglycerides and cholesterol esters. This
      means that liver peroxidation induced by ethanol can not completely account for
      the liver pathology or the decrease in arachidonic acid caused by ethanol. Lauric
      acid omega-1 hydroxidation by the liver microsomes in vitro was increased by
      ethanol and partially blocked by CYP2E1 inhibitors. However, although ethanol
      feeding increased the total hydroxidation and epoxidation of arachidonic acid,
      these were not inhibited by CYP2E1 inhibitors. Thus the ethanol-induced
      arachidonic acid depletion is not likely due to CYP2E1 metabolism of arachidonic
      acid, since the severity of liver pathology correlated negatively with the
      decrease in arachidonic acid in the ethanol-fed rats. The increase in its
      metabolism by microsomes and decrease in synthesis may be an important mechanism
      of ethanol-induced liver injury.

PMID- 9164262
TI  - Dietary modulation of oxidative stress in alcoholic liver disease in rats.
AB  - Numerous studies dealing with prolonged feeding of rats with ethanol liquid
      regimens high in fat and low in carbohydrate showed that the resulting hepatic
      pathologic changes, including increased lipid peroxidation, are due to dietary
      aberrations rather than to ethanol toxicity. The amount and particularly the type
      of dietary fat significantly modulate the hepatic oxidative stress and
      morphofunctional reactivities. Although dietary vitamin E modulated oxidative
      stress or lipid peroxidation, it did not influence the development of hepatic
      pathologic changes in different animal models of chronic alcoholism. The old
      observation that lipotropes modulate the hepatic alterations associated with
      prolonged excessive ingestion of ethanol has been amply confirmed by even those
      who for years did not accept the importance of lipotropes. Our recent studies in
      rats indicated that prolonged feeding of large amounts of ethanol and diets with
      variable amounts of lipotropes, vitamin E and minerals did not significantly
      modulate a large series of hepatic prooxidants, but decreased several
      antioxidants (vitamin E, ubiquinols and glutathione peroxidase). Ethanol regimens
      relatively low in vitamin E increased the hepatic thiobarbituric acid-reactive
      substances and chemiluminescence and reduced some of the antioxidant factors.
      However, the hepatic prooxidant factors were unaffected, and no liver damage was
      detected. These and other findings indicated that the eventual detection of
      oxidative stress in experimental alcoholic liver disease primarily depends on the
      type of diet and that oxidative stress may not play a significant pathogenic role
      in this condition.

PMID- 9164263
TI  - Diet, anthropometry and breast cancer: integration of experimental and
      epidemiologic approaches.
AB  - The interrelation ships of dietary fat and energy, growth rates and
      anthropometry, and breast carcinogenesis have been examined by a diverse array of
      approaches throughout the last 50 y as new investigative tools have been
      developed by laboratory scientists and epidemiologists. A consensus among
      investigators has not emerged, however, and dietary recommendations for breast
      cancer prevention have not been clearly formulated or effectively communicated to
      the public. Indeed, the gap between those investigators utilizing laboratory
      based approaches and those using epidemiologic models has expanded in recent
      years. Cancer epidemiologists have become increasingly skeptical that results
      derived form laboratory animal models of breast carcinogenesis and in vitro
      systems are directly applicable to human breast cancer risk. Concurrently,
      laboratory scientists have questioned the ability of epidemiological tools to
      accurately measure dietary intake and relevant biomarkers and to account for a
      diverse array of potentially confounding environmental and genetic factors
      characteristic of human populations under study. These polarized views are
      reinforced by a failure of investigators using diverse approaches to interact,
      integrate their skills and resources, develop novel hypotheses, and propose
      solutions using both laboratory and epidemiologic techniques. Therefore, the
      objectives of this symposium are to summarize experimental and epidemiologic
      knowledge, foster communication and collaboration, and attempt to identify
      appropriate studies to bridge the gaps in our knowledge concerning dietary lipid
      and energy, anthropometrics, and breast cancer risk.

PMID- 9164264
TI  - Fat, energy and breast cancer.
AB  - Rates of breast cancer vary approximately fivefold among countries and are
      strongly correlated with national per capita availability of dietary fat.
      However, this relation may be substantially confounded by many other factors
      associated with affluent lifestyles, such as reduced parity and physical
      activity. In large prospective epidemiologic studies, little evidence has been
      seen to support any major positive association between dietary fat and risk of
      breast cancer over the range of 15-45% or more of energy from fat. The
      observation that women in counties in China consuming approximately 25% of energy
      from fat have much lower rates of breast cancer than U.S. women with similar fat
      intakes provides additional evidence that factors other than dietary fat account
      for the large international differences. Some epidemiologic evidence suggests
      that monounsaturated fat and olive oil in particular may reduce risk of breast
      cancer when substituted for other types of fat. In contrast to findings for
      dietary total fat, most types of epidemiologic studies provide indirect support
      for a protective effect of energy restriction and reduced growth rates against
      breast cancer, which is consistently observed in animal studies of mammary
      carcinogenesis.

PMID- 9164265
TI  - Anthropometry and breast cancer.
AB  - Relatively consistent findings about the relationships between body size and
      shape and breast cancer risk have been emerging in recent years. Adult height is
      predictive of breast cancer risk, even in populations with no evidence of energy
      or nutrient deficiency. A complex relationship with adiposity has been observed.
      The dominant pattern is increasing risk with increasing adiposity except in
      younger, premenopausal women from countries with high breast cancer rates, in
      whom an inverse association is noted. When adult weight is evaluated as a dynamic
      measurement rather than a constant one, excess weight in the years preceding
      breast cancer diagnosis seems especially critical, consistent with the
      substantial evidence that adiposity at the time of breast cancer diagnosis is
      associated with an increased probability of recurrence and a decreased survival
      time. Adult weight gain has consistently predicted increased risk of breast
      cancer in older, postmenopausal women, even in some studies in which adult
      adiposity was only weakly associated with risk. In several studies, women with
      increased abdominal fat deposition, or central adiposity, also had an elevated
      risk of postmenopausal, though not necessarily premenopausal, breast cancer,
      independent of their adult adiposity. These patterns suggest that lifestyles
      leading to a positive energy balance are involved in the etiology of this disease
      and that energy intake and physical activity may be especially influential. The
      hormonal and metabolic mechanisms that account for these relationships between
      body size and shape and breast cancer risk are not adequately understood and
      merit further study.

PMID- 9164266
TI  - Genetic factors in the pathogenesis of breast cancer: their role and relative
      importance.
AB  - Aggregation of breast cancer in families is an established risk factor associated
      with increased incidence of the disease, which is a leading cause of morbidity
      and mortality among women in this country. Three genes have now been identified
      that confer increased susceptibility in families with a clear hereditary (i.e.,
      Mendelian) pattern of expression: BRCA1, BRCA2 and p53. However, a significant
      number of women have an identified family history of breast cancer without clear
      Mendelian patterns of disease. Such patterns are consistent with the effect of
      more common genes with lower associated risk. Some evidence is available to
      implicate three additional genes that fit this category: AT, ESR and HRAS1. An
      area of active interest is genetically mediated variation in the metabolism of
      estrogens, a process controlled by several genes, each with more modest effects.
      The interaction of genes and environmental factors in breast cancer pathogenesis
      is of considerable public health importance.

PMID- 9164267
TI  - Diet and breast cancer: studies in laboratory animals.
AB  - Increasing dietary fat content increases mammary gland tumorigenesis in
      laboratory rodents. The effect can be attributed only in part to increasing
      energy intake, which itself increases tumorigenesis. Restriction of dietary or
      energy intake, sufficient to reduce body weight, reduces mammary gland
      tumorigenesis. Consideration of these effects has led to discussion of the
      possible need for changes in the feeding of laboratory rodents in carcinogenesis
      bioassays and other chronic studies. Studies of endocrine or other growth factors
      for the mammary gland have not identified specific effects of dietary fat or
      energy. In addition, tumorigenesis in other organs responds similarly to
      increased fat or decreased energy intake, indicating that the mechanisms are not,
      or not entirely, specific for the mammary gland. Extrapolations of results
      between species must always be made with caution, but the marked effects of
      dietary fat and energy in rodent tumorigenesis models must be considered in
      designing diet advice for humans.

PMID- 9164268
TI  - Perspectives on integrating experimental and epidemiologic research on diet,
      anthropometry and breast cancer.
AB  - Three perspectives on the integration of experimental and epidemiologic research
      on diet, anthropometry and breast cancer are presented. 1) Although body weight
      and height have been linked to breast cancer risk by epidemiologic research,
      their roles have not been directly explored with animal models. However, basic,
      clinical and epidemiologic research on obesity and associated metabolic
      alterations may be pertinent. Individual differences in the timing and magnitude
      of weight gain and loss during adult life need to be considered in epidemiologic
      studies of adiposity and breast cancer, along with individual differences in the
      pattern of body fat deposition, the hormonal and metabolic changes that accompany
      the adiposity, and family history of obesity-related chronic diseases. Animal
      models with genetic predispositions to obesity, diabetes and breast cancer merit
      further exploration, as well as models that can evaluate exposures occurring
      after puberty. 2) The synergy between experimental and epidemiologic studies on
      fat and energy intake and breast carcinogenesis has been productive because each
      discipline has had to incorporate recent findings of the other. Dietary studies
      utilizing animals with different genetic profiles are promising, but require
      identification of the critical genes in human carcinogenesis. 3) Controlled
      dietary intervention studies with human participants using intermediate endpoints
      can bridge the gap between animal and epidemiologic studies, but generally
      accepted intermediate endpoints for breast cancer need to be developed. Such
      studies would permit better control of diet than large clinical trials and the
      opportunity to explore mechanisms.

PMID- 9164269
TI  - Progress in understanding the genetics of obesity.
AB  - Progress in understanding the genetics of obesity has moved rapidly in the past
      few years. The genes for all of the single gene defects that produce obesity in
      experimental animals have now been cloned. The new insights from these models are
      one spur for the examination of possible links to human obesity. In thinking
      about the biology of obesity produced by single gene defects, it must be kept in
      mind that adrenalectomy can prevent the phenotypic expression in all of the
      single gene models of obesity. Thus, nongenetic components can play a major role
      in regulating even single gene models of obesity. Transgenic mice have also
      expanded our understanding of obesity. Transgenic models that both increase and
      decrease body fat have been published. Of particular interest from the
      perspective of the physiological control of obesity is the destruction of the
      uncoupling protein in brown adipose tissue, which is followed by hyperphagia and
      obesity, suggesting that the sympathetic nervous system is involved in both
      modulation of food intake and energy storage. Gene mapping using quantitative
      trait loci and studies of candidate genes have been applied to experimental
      models of animals with differing susceptibilities to dietary fat and have been
      applied to the human genome in more detail.

PMID- 9164270
TI  - Genetic influences on the response of body fat and fat distribution to positive
      and negative energy balances in human identical twins.
AB  - This article summarizes a series of intervention studies conducted with pairs of
      young adult male identical twins and designed to determine whether there is any
      evidence for genotype x overfeeding or genotype x negative energy balance
      interaction effects in the changes in body weight, body composition, fat
      distribution, computerized tomography-assessed abdominal visceral fat, resting
      metabolic rate and thermic response to a standardized meal of mixed composition
      brought about by chronic exposure to appropriate experimental treatments. These
      studies demonstrated that individual differences in response to chronic
      alterations in energy balance are common. The comparison of the heterogeneity in
      response between the pairs of twins in contrast to the variance within pairs
      revealed that members of the same twin pair are significantly more alike than
      individuals who are not genetically related by descent. The intrapair resemblance
      in response was particularly strong for the changes in body mass, body
      composition, subcutaneous fat distribution and abdominal visceral fat. In
      contrast, the results of two long-term intervention studies showed that
      variations in resting metabolic rate following exposure to chronic overfeeding or
      negative energy balance induced by exercise were accounted for primarily by the
      changes in body mass. Finally, the thermic response to food was not modified by
      any of the experimental treatments. On the basis of these observations, we
      conclude that there are individuals at risk of gaining weight and body fat or who
      are resistant to weight loss. These differences in susceptibility to chronic
      overfeeding or in sensitivity to negative energy balance seem to be largely
      explained by genetic factors whose exact nature remains to be determined.

PMID- 9164271
TI  - Nutrition and newly emerging viral diseases: an overview.
AB  - Infectious diseases are on the increase worldwide. When discussing interactions
      of nutrition and infection, nutritionists have traditionally considered only the
      effects of diet on the host. Recent data, however, indicate that, at least for an
      RNA virus, host nutriture can influence the genetic make-up of the pathogen and
      thereby alter its virulence. This symposium was organized to alert the nutrition
      community to this discovery and its possible implications for the investigation
      of nutrition-infection interrelationships. Topics covered in the symposium
      include the following: the public health threat of emerging viral diseases; the
      rapid evolution of viral RNA genomes; oxidants and antioxidants in viral diseases
      disease mechanisms and metabolic regulation; and increased virulence of
      coxsackievirus B3 due to vitamin E or selenium deficiency. If the findings with
      coxsackievirus are more broadly applicable to other RNA viruses, the results
      could be of great public health significance because RNA viruses constitute the
      majority of all plant, animal and human viruses.

PMID- 9164272
TI  - The public health threat of emerging viral disease.
AB  - "Emerging diseases" are those that either have newly appeared in the population
      or are rapidly increasing their incidence or expanding their geographic range.
      Emerging viruses usually have identifiable sources, often existing viruses of
      animals or humans that have been given opportunities to infect new host
      populations ("viral traffic"). Environmental and social changes, frequently the
      result of human activities, can accelerate viral traffic, with consequent
      increases in disease emergence. Host factors, including nutrition, have often
      received less attention in the past but are of considerable importance. These
      factors, combined with the ongoing evolution of viral and microbial variants,
      make it likely that emerging infections will continue to appear and probably
      increase, emphasizing the need for effective surveillance.

PMID- 9164273
TI  - Rapid evolution of viral RNA genomes.
AB  - Mutation rates during RNA virus replication are several orders of magnitude
      larger than those operating during replication of cellular DNA. This results in
      the continuous generation of mutant genomes and in their rating in competition
      with other variants present and arising in the population. The dynamic mutant
      distributions that constitute RNA virus populations are termed quasispecies. This
      concept has facilitated links between population genetics and virology and has a
      number of important implications for viral pathogenesis and the control of viral
      disease. One of them is that the mutant spectra in RNA viruses constitute large
      reservoirs of genetic and phenotypic variants with potentially altered biological
      properties. Individual mutants kept in a low proportion under a set of
      environmental conditions may become dominant following an environmental change.
      Relevant to this review are possible links between the alteration of quasispecies
      distributions and nutritional deficiencies and oxidative stress in cells. In
      addition to being a possible mechanism of viral pathogenesis, oxidative stress,
      and other environmental modifications resulting from nutritional imbalances, may
      promote population disequilibrium in replicating viruses. In particular, the
      increased mutagenesis mediated by oxidative DNA damage could also affect
      replicating RNA and integrated provirus, extending the mutant repertoire of
      viruses. Also, the impairment of humoral and cellular immune functions may delay
      or prevent viral clearance, leading to an expanded representation of viral
      mutants in the infected organism. Thus, nutritional deficiencies are a potential
      source of viral mutants with altered biological properties.

PMID- 9164274
TI  - Oxidants and antioxidants in viral diseases: disease mechanisms and metabolic
      regulation.
AB  - Reactive oxygen and nitrogen metabolites play a complex role in many diseases and
      in metabolic regulation. Because viruses replicate in living cells, such
      metabolites influence the growth of viruses in addition to serving as a host
      defense mechanism. Low levels of reactive oxygen species (ROS) play a role in
      mitogenic activation, and the early phase of lytic and nonlytic virus infection
      indeed resembles that of mitogenic cell activation. In addition to these subtle
      cell-activating effects shared by many viruses, influenza and paramyxoviruses
      activate a respiratory burst in phagocytic cells. These viruses are toxic when
      injected in animals. Cells lavaged from the lungs of mice infected with influenza
      virus are primed for enhanced superoxide generation. Moreover, xanthine oxidase
      is enhanced and the buffering capacity of small molecular antioxidants is
      decreased in the lungs, suggesting that infection leads to oxidative stress. The
      wide array of cytokines produced in the lungs during influenza could contribute
      to the systemic effects of influenza. Oxidative stress has also been shown in
      human immunodeficiency virus (HIV) infection in humans. Via activation of NF
      kappa B, ROS may activate viral replication, but oxidants are believed to
      contribute also to the loss of CD4 T cells by apoptosis. Antioxidants, together
      with agents interfering with the harmful effects of cytokines and lipid
      mediators, may have a role in the treatment of viral diseases. Such agents could
      not only alleviate disease symptoms but also decrease the long-term effects of
      chronic oxidative stress, which have been linked to the development of cancer in
      some viral infections.

PMID- 9164275
TI  - Increased virulence of coxsackievirus B3 in mice due to vitamin E or selenium
      deficiency.
AB  - Nutrition has long been known to affect the ability of the host to respond to
      infectious disease. Widespread famines are often accompanied by increased
      morbidity and mortality due to infectious diseases. The currently accepted view
      of the relationship between nutrition of the host and its susceptibility to
      infectious disease is one of a direct relationship with host immune status. That
      is, if the nutritional status of the host is poor-due to either single or
      multiple nutrient deficiencies-then the functioning of the host immune system is
      compromised. This impairment of the immune response will lead to an increased
      susceptibility to infectious disease. Clearly, the immune response has been shown
      to be weakened by inadequate nutrition in many model systems and in human
      studies. However, what about the effect of host nutrition on the pathogen itself?
      Our laboratory has shown, using a mouse model of coxsackievirus-induced
      myocarditis, that a host deficiency in either selenium or vitamin E leads to a
      change in viral phenotype, such that an avirulent strain of the virus becomes
      virulent and a virulent strain becomes more virulent. The change in phenotype was
      shown to be due to point mutations in the viral genome. Once the mutations occur,
      the phenotype change is stable and can now be expressed even in mice of normal
      nutriture. Our results suggest that nutrition can affect not only the host, but
      the pathogen as well, and demonstrate a new model of relating host nutritional
      effects to viral pathogenesis.

PMID- 9164276
TI  - Should infant formulas be supplemented with bioactive components and
      conditionally essential nutrients present in human milk?

PMID- 9164277
TI  - Is milk-borne insulin-like growth factor-I essential for neonatal development?
AB  - Insulin-like growth factor-I (IGF-I), a polypeptide growth factor found in milk,
      is hypothesized to play a functional role in the growth and development of
      neonates, particularly the gastrointestinal tract. Considerable evidence, based
      on direct tracer studies with 125I-labeled IGF-I and measurements of circulating
      IGF-I concentrations in neonatal animals fed a range of IGF-I doses, indicates
      that the intestinal absorption of IGF-I and the possible effect on metabolism and
      somatic growth are negligible. However, studies in neonatal animals indicate that
      oral administration of pharmacological doses of IGF-I increases small intestinal
      mucosal growth, whereas oral IGF-I provided within the physiological range may
      enhance the development of intestinal lactase. Therefore, clinical trials
      exploring the therapeutic use of oral IGF-I as an intervention for preterm
      neonates and those with compromised intestinal function seem warranted. However,
      milk-borne IGF-I may not be essential for normal healthy infants, perhaps because
      endogenous IGF-I provides a sufficient stimulus for maintenance of
      gastrointestinal structure and function. Future studies should explore the
      significance of endogenous IGF-I and whether milk-borne IGF-I may be important
      under pathological conditions in which the endogenous IGF-I production may be
      compromised.

PMID- 9164278
TI  - Do the binding properties of oligosaccharides in milk protect human infants from
      gastrointestinal bacteria?
AB  - The oligosaccharide fraction of human milk, the third most abundant solid
      constituent, consists of hundreds of structures, many of them fucosylated.
      Oligosaccharides may bear structural homology to cell surface glycoconjugates
      used as receptors by pathogens, thus protecting nursing infants. The ability of
      human milk to protect against heat-stable enterotoxin of Escherichia coli in
      suckling mice has been attributed to neutral fucosylated oligosaccharides of
      milk. The same phenomenon has been found in human T84 cells, allowing the
      mechanism of inhibition by the oligosaccharide to be studied in vitro. The
      oligosaccharide binds to the extracellular domain of guanylyl cyclase, thereby
      inhibiting the binding of stable toxin. The protective oligosaccharide is a large
      structure present in too low a concentration to be routinely measured directly;
      however, its concentration in milk may be inferred by measuring smaller, more
      plentiful, structurally homologous oligosaccharides. The adhesion by invasive
      pathogenic strains of Campylobacter to their enterocyte target is also inhibited
      by human milk fucosyloligosaccharides. Because Campylobacter binds H-2 type
      oligosaccharide structures, the concentration of protective oligosaccharide may
      also be inferred from the total oligosaccharide profile. The relationship between
      oligosaccharide profile heterogeneity in human milk and the incidence of specific
      gastrointestinal bacterial disease in infants consuming these milks could
      indicate the significance of these oligosaccharides to infant health. The
      efficacy of synthetic analogs of active oligosaccharides will confirm their
      clinical relevance and define minimum structural features essential for activity.

PMID- 9164279
TI  - Do milk-borne cytokines and hormones influence neonatal immune cell function?
AB  - Cytokines, growth factors and various hormones collectively control the
      proliferation, survival, differentiation and function of immune cells. A wide
      array of these compounds is present in maternal milk and ingested by neonates
      during a period of rapid maturation of gut-associated and peripheral lymphoid
      tissues. The functional consequences of most milk immunomodulatory constituents
      in neonates are unknown. However, there is evidence that milk prolactin acts as a
      developmental regulator of the neonatal immune system, supporting the premise
      that milk constituents with immunomodulatory activity may serve as neonatal
      immunodevelopment agents.

PMID- 9164280
TI  - Sarcopenia: origins and clinical relevance.
AB  - This presentation reflects on the origins of the term sarcopenia. The Greek roots
      of the word are sarx for flesh and penia for loss. The term actually describes
      important changes in body composition and related functions. Clearly defining
      sarcopenia will allow investigators to appropriately classify patients and
      examine underlying pathogenic mechanisms and will allow funding agencies to
      appropriately target research funds to a taxonomically distinct syndrome.

PMID- 9164281
TI  - Significance of sarcopenia in the elderly.
AB  - At the present time, there is only limited understanding of the public health
      significance of sarcopenia. The well-recognized functional consequences of
      sarcopenia include gait and balance problems and increased risk for fall.
      Ultimately, these impairments can lead to the loss of physical functional
      independence. However, sarcopenia may also contribute to an increased risk for
      chronic diseases such as diabetes and osteoporosis. Future studies of the
      pathophysiologic significance of sarcopenia need to consider the contribution(s)
      of muscle properties (e.g., muscle fiber composition, muscle blood flow, fatigue
      characteristics, innervation) to alterations in physical performance, metabolism
      and physiology, and skeletal health. More comprehensive studies on the sequelae
      of sarcopenia are critical to an accurate assessment of the public health burden
      that sarcopenia poses to the elderly population.

PMID- 9164282
TI  - Sarcopenia: assessment of muscle mass.
AB  - Despite general information that skeletal muscle mass is the largest organ in the
      body and despite increased awareness of the importance of skeletal muscle in
      biological function, methods and techniques for its routine assessment in humans
      are generally lacking. One important reason for the paucity of assessment tools
      is the relative lack of direct data on anatomical skeletal muscle mass in humans.

PMID- 9164283
TI  - Functional and metabolic consequences of sarcopenia.
AB  - The capacity of older men and women to adapt to regularly performed exercise has
      been demonstrated by many laboratories. Aerobic exercise results in improvements
      in functional capacity and reduced risk of developing type II diabetes in the
      elderly. High intensity resistance training (above 60% of the 1 repetition
      maximum) causes large increases in strength in the elderly, and resistance
      training significant increases muscle size. Resistance training also
      significantly increases energy requirements and insulin action of the elderly. We
      recently demonstrated that resistance training has a positive effect on multiple
      risk factors for osteoporotic fractures in previously sedentary post-menopausal
      women. Because the sedentary lifestyle of individuals in a long-term care
      facility may exacerbate losses of muscle function, we applied this same training
      program to frail, institutionalized elderly men and women. In a population of 100
      nursing home residents, a randomly assigned high intensity strength training
      program resulted in significant gains in strength and functional status. In
      addition, spontaneous activity, measured by activity monitors, increased
      significantly in those participating in the exercise program; there was no change
      in the sedentary control group. Before the strength training intervention, the
      relationship of whole-body potassium and leg strength was relatively weak (r2 =
      0.29, P < 0.001), indicating that in very old persons muscle mass is an important
      but not the only determiner of functional status. Thus exercise may minimize or
      reverse the syndrome of physical frailty prevalent among very old individuals.
      Because of their low functional status and high incidence of chronic disease,
      there is no segment of the population that can benefit more from exercise
      training than the elderly.

PMID- 9164284
TI  - Muscle mass and strength: relation to function in population studies.
AB  - The use of the term sarcopenia to describe the age-related loss in skeletal
      muscle and its functional consequences is relatively recent. However, interest in
      the relationship of muscle mass to strength and function predates the concept of
      sarcopenia as researchers have attempted to understand differences in mass and
      strength between men and women, young and old. Most of these studies are cross
      sectional comparisons in which muscle mass and strength tend to be linearly
      related, so that those with more muscle tend to be stronger. This article focuses
      instead on some potential problems with the sarcopenia-function association in
      old age and presents what little data exist from longitudinal population studies
      addressing the effect of sarcopenia over time.

PMID- 9164285
TI  - Transcription factor polyomavirus enhancer activator protein 3 (PEA3) is induced
      in adult rats following muscle injury.
AB  - Following muscle damage, activation of adult myoblasts (also called satellite
      cells) is an important aspect of muscle regeneration. Upon activation, satellite
      cells proliferate, migrate to the site of injury, and become competent to fuse
      and differentiate, thereby regenerating damaged fibers. We show here that the
      transcription factor polyomavirus enhancer activator protein 3 (PEA3) is
      expressed in adult myoblasts in vitro when they are proliferative and during the
      early stages of differentiation. In young adult rat muscle in vivo, PEA3 is
      detectable in satellite cells only following muscle damage, suggesting that PEA3
      is involved in regulating activated satellite cell gene expression. In contrast,
      PEA3 is expressed in undamaged muscle from aged rats and demonstrates a more
      dramatic increase following muscle injury. Thus, during muscle aging, satellite
      cells may become chronically activated but are still able to respond to signals
      resulting from muscle damage.

PMID- 9164286
TI  - Evidence for nervous system degeneration with advancing age.
AB  - Human skeletal muscle undergoes major structural and functional changes with
      advancing age. A progressive degeneration of the nervous system is now considered
      a major factor underlying these alterations. This review will briefly describe
      the changes that occur in the human motor unit with increasing age and focus
      specifically on the changes that relate to a degeneration of the nervous system.

PMID- 9164287
TI  - Inflammatory and hormonal mediators of cachexia.
AB  - Body composition is a reflection of the metabolic state of the organism. However,
      because the time course of change in body composition is slower than that of
      metabolic processes, measurement of body composition offers a unique way of
      assessing the organism's physiologic status. The hormonal and immune mediators
      that control metabolism, and thus body composition, can be divided into three
      categories: day-to-day regulators (insulin and glucagon), life cycle-related
      hormones (estrogens and androgens, growth hormone, prolactin, thyroid hormones,
      catecholamines, corticosteroids) and immunologic mediators (the cytokines
      interleukin-1, tumor necrosis factor, and interleukin-6). Although the cytokines
      can clearly drive metabolism and thus body composition in various illnesses, it
      is not yet clear whether they also play a homeostatic role in the age-related
      changes in body composition that we now call sarcopenia.

PMID- 9164288
TI  - Experiments that changed nutritional thinking. Proceedings of a minisymposium.
      Atlanta, Georgia, April 1995 and Washington, DC, April 1996.

PMID- 9164289
TI  - The liver forms, stores and secretes glucose (Claude Bernard, 1860).

PMID- 9164290
TI  - Protein cannot be the sole source of muscular energy (Fick, Wislicenus and
      Frankland, 1866).

PMID- 9164291
TI  - Inorganic iron can be used to build hemoglobin (Stockman, 1893).

PMID- 9164292
TI  - A micronutrient deficiency in chickens (Grijns, 1896-1901).

PMID- 9164293
TI  - Dietary protein standards can be halved (Chittenden, 1904).

PMID- 9164294
TI  - Liebig's concept of nutritional adequacy challenged (Hart et al., 1911).

PMID- 9164295
TI  - Young rats need unknown growth factors (McCollum, 1913-1917).

PMID- 9164296
TI  - Some amino acids are indispensable for growth (Osborne and Mendel, 1914-1916).

PMID- 9164297
TI  - Pellagra is not infectious! (Goldberger, 1916).

PMID- 9164298
TI  - Copper as a supplement to iron for hemoglobin building in the rat (Hart et al.,
      1928).

PMID- 9164299
TI  - The conversion of carotene to vitamin A (Thomas Moore, 1930).

PMID- 9164300
TI  - The co-enzyme function of thiamin (Peters et al., 1929-1937).

PMID- 9164301
TI  - To live longer, eat less! (McCay, 1934-1939).

PMID- 9164302
TI  - The dynamic state of body constituents (Schoenheimer, 1939).

PMID- 9164303
TI  - Tryptophan's role as a vitamin precursor (Krehl et al., 1945).

PMID- 9164304
TI  - The concept of trace element antagonism: the Cu-Mo-S triangle (Dick, 1952-1954).

PMID- 9164305
TI  - Reduced radiation damage from ingestion of cabbage family plants.

PMID- 9164306
TI  - Toxicity of sucrose and fructose for neonatal pigs (Becker et al. 1954).

PMID- 9164307
TI  - Discovery of the vitamin D endocrine system.

PMID- 9164308
TI  - Glutathione peroxidase: a role for selenium (Rotruck 1972).

PMID- 9164309
TI  - Quite right, Mrs Crick.

PMID- 9164310
TI  - Hidden dangers of incompletely suppressive antiretroviral therapy.

PMID- 9164311
TI  - In search of a superaspirin for the heart.

PMID- 9164312
TI  - A useful collagenous colitis registry.

PMID- 9164313
TI  - Sponsorship, authorship, and a tale of two media.

PMID- 9164314
TI  - Randomised trial of addition of lamivudine or lamivudine plus loviride to
      zidovudine-containing regimens for patients with HIV-1 infection: the CAESAR
      trial.
AB  - BACKGROUND: Previous studies have shown that combination therapy with lamivudine
      plus zidovudine causes pronounced and sustained increases in CD4 counts and
      reductions in viral load in individuals infected with HIV-1. We assessed the
      clinical benefit of the addition of lamivudine to zidovudine-based regimens in
      patients infected with HIV-1 who had CD4 counts of 25-250/microL. METHODS:
      Eligible patients receiving zidovudine monotherapy or zidovudine plus zalcitabine
      or didanosine combination therapy were assigned 52 weeks of treatment with the
      addition of placebo, lamivudine (150 mg twice a day), or lamivudine (150 mg twice
      a day) plus loviride (100 mg three times a day). Patients were unaware of type of
      treatment allocated. The primary endpoint was progression to a new protocol
      defined AIDS event or death. FINDINGS: The study was terminated following the
      second interim analysis because of a highly significant reduction in progression
      to AIDS or death in the patients treated with lamivudine rather than placebo. In
      the final analysis of 1840 patients, progression had occurred in 95 (20%) of 471
      placebo-treated patients, 86 (9%) of 907 lamivudine-treated patients, and 42 (9%)
      of 462 patients who received lamivudine plus loviride (p < 0.0001, relative
      hazard 0.42 [95% CI 0.32-0.57]). A significant survival benefit was also seen (p
      = 0.0007, relative hazard 0.40 [0.23-0.69]). Significantly fewer patients in the
      lamivudine group than in the placebo group required hospital admission,
      unscheduled visits, or prescribed medications for HIV-related events. There were
      no differences in the frequency or severity of clinical or laboratory toxicities
      between the treatment groups. INTERPRETATION: The addition of lamivudine to
      zidovudine-containing treatment regimens significantly slowed the progression of
      HIV disease and improved survival. However, it is unlikely that this combination
      alone would be sufficient to achieve long-term complete suppression of viral
      replication in all patients.

PMID- 9164315
TI  - Randomised placebo-controlled trial of effect of eptifibatide on complications of
      percutaneous coronary intervention: IMPACT-II. Integrilin to Minimise Platelet
      Aggregation and Coronary Thrombosis-II.
AB  - BACKGROUND: Platelet-mediated thrombosis has been implicated in the development
      of ischaemic complications of percutaneous coronary intervention. We investigated
      whether inhibition of the platelet glycoprotein IIb/IIIa integrin with
      eptifibatide (Integrilin) could prevent such complications. METHODS: We undertook
      a double-blind, placebo-controlled trial at 82 centres in the USA, enrolling 4010
      patients undergoing elective, urgent, or emergency coronary intervention.
      Patients were assigned one of three treatments: placebo (n = 1328), a bolus of
      135 micrograms/kg eptifibatide followed by an infusion of 0.5 microgram kg-1 min
      1 for 20-24 h (n = 1349), or 135 micrograms/kg eptifibatide bolus with a 0.75
      microgram kg-1 min-1 infusion (n = 1333). The coronary procedure was started
      within 10-60 min of the start of study treatment. The primary endpoint was the 30
      day composite occurrence of death, myocardial infarction, unplanned surgical or
      repeat percutaneous revascularisation, or coronary stent implantation for abrupt
      closure (by intention to treat). The primary safety endpoint was major bleeding.
      FINDINGS: By 30 days, the composite endpoint had occurred in 151 (11.4%) patients
      in the placebo group compared with 124 (9.2%) in the 135/0.5 eptifibatide group
      (p = 0.063) and 132 (9.9%) in the eptifibatide 135/0.75 group (p = 0.22). By
      treatment-received analysis, the 135/0.5 regimen produced a significant reduction
      in the composite endpoint (11.6 vs 9.1%, p = 0.035), but the 135/0.75 regimen
      produced a less substantial reduction (11.6 vs 10.0%, p = 0.18). Eptifibatide
      treatment did not increase rates of major bleeding or transfusion.
      INTERPRETATION: In the 135/0.5 group, treatment with eptifibatide during coronary
      intervention reduced rates of early abrupt closure and ischaemic events at 30
      days. Non-significant differences were seen with the 135/0.75 regimen. The doses
      studied thus appear to be at the low end of the efficacy-response curve. Further
      investigation to refine eptifibatide dosing during coronary intervention is
      warranted.

PMID- 9164316
TI  - Randomised placebo-controlled trial of abciximab before and during coronary
      intervention in refractory unstable angina: the CAPTURE Study.
AB  - BACKGROUND: Platelet aggregation is a dominant feature in the pathophysiology of
      unstable angina. Percutaneous transluminal coronary angioplasty (PTCA) in
      patients with this disorder carries an increased risk of thrombotic
      complications. Abciximab (c7E3) blocks the platelet glycoprotein IIb/IIIa
      receptor, thus preventing platelet adhesion and aggregation. The CAPTURE study
      was a randomised placebo-controlled multicentre trial to assess whether abciximab
      can improve outcome in patients with refractory unstable angina who are
      undergoing PTCA. METHODS: The study recruited patients with refractory unstable
      angina, defined as recurrent myocardial ischaemia under medical treatment
      including heparin and nitrates. Predefined stopping rules were met at a planned
      interim analysis of data for 1050 patients, and recruitment was stopped. Data for
      1265 patients (of 1400 scheduled) are presented here. After angiography, patients
      received a randomly assigned infusion of abciximab or placebo for 18-24 h before
      PTCA, continuing until 1 h afterwards. The primary endpoint was the occurrence
      within 30 days after PTCA of death (any cause), myocardial infarction, or urgent
      intervention for recurrent ischaemia. Analyses were by intention to treat.
      FINDINGS: By 30 days, the primary endpoint had occurred in 71 (11.3%) of 630
      patients who received abciximab compared with 101 (15.9%) of 635 placebo
      recipients (p = 0.012). The rate of myocardial infarction was lower in the
      abciximab than in the placebo group before PTCA (four [0.6%] vs 13 [2.1%], p =
      0.029) and during PTCA (16 [2.6%] vs 34 [5.5%], p = 0.009). Major bleeding was
      infrequent, but occurred more often with abciximab than with placebo (24 [3.8%]
      vs 12 [1.9%], p = 0.043). At 6-month follow-up, death, myocardial infarction, or
      repeat intervention had occurred in 193 patients in each group. INTERPRETATION:
      In patients with refractory unstable angina, treatment with abciximab
      substantially reduces the rate of thrombotic complications, in particular
      myocardial infarction, before, during, and after PTCA. There was no evidence that
      this regimen influenced the rate of myocardial infarction after the first few
      days, or the need for subsequent reintervention.

PMID- 9164317
TI  - Global mortality, disability, and the contribution of risk factors: Global Burden
      of Disease Study.
AB  - BACKGROUND: Prevention and control of disease and injury require information
      about the leading medical causes of illness and exposures or risk factors. The
      assessment of the public-health importance of these has been hampered by the lack
      of common methods to investigate the overall, worldwide burden. The Global Burden
      of Disease Study (GBD) provides a standardised approach to epidemiological
      assessment and uses a standard unit, the disability-adjusted life year (DALY), to
      aid comparisons. METHODS: DALYs for each age-sex group in each GBD region for 107
      disorders were calculated, based on the estimates of mortality by cause,
      incidence, average age of onset, duration, and disability severity. Estimates of
      the burden and prevalence of exposure in different regions of disorders
      attributable to malnutrition, poor water supply, sanitation and personal and
      domestic hygiene, unsafe sex, tobacco use, alcohol, occupation, hypertension,
      physical inactivity, use of illicit drugs, and air pollution were developed.
      FINDINGS: Developed regions account for 11.6% of the worldwide burden from all
      causes of death and disability, and account for 90.2% of health expenditure
      worldwide. Communicable, maternal, perinatal, and nutritional disorders explain
      43.9%; non-communicable causes 40.9%; injuries 15.1%; malignant neoplasms 5.1%;
      neuropsychiatric conditions 10.5%; and cardiovascular conditions 9.7% of DALYs
      worldwide. The ten leading specific causes of global DALYs are, in descending
      order, lower respiratory infections, diarrhoeal diseases, perinatal disorders,
      unipolar major depression, ischaemic heart disease, cerebrovascular disease,
      tuberculosis, measles, road-traffic accidents, and congenital anomalies. 15.9% of
      DALYs worldwide are attributable to childhood malnutrition and 6.8% to poor
      water, and sanitation and personal and domestic hygiene. INTERPRETATION: The
      three leading contributors to the burden of disease are communicable and
      perinatal disorders affecting children. The substantial burdens of
      neuropsychiatric disorders and injuries are under-recognised. The epidemiological
      transition in terms of DALYs has progressed substantially in China, Latin America
      and the Caribbean, other Asia and islands, and the middle eastern crescent. If
      the burdens of disability and death are taken into account, our list differs
      substantially from other lists of the leading causes of death. DALYs provide a
      common metric to aid meaningful comparison of the burden of risk factors,
      diseases, and injuries.

PMID- 9164319
TI  - Playing in a scrapyard and acute renal failure.

PMID- 9164318
TI  - Cytomegalovirus retinitis after initiation of highly active antiretroviral
      therapy.
AB  - BACKGROUND: In previous natural history studies and clinical trials, AIDS-related
      cytomegalovirus (CMV) retinitis has occurred primarily in patients with absolute
      CD4 counts of 50 cells/microL or less (0.05 x 10(9)/L) at the time of diagnosis.
      METHODS: We report five patients identified from our clinical practices who were
      diagnosed with CMV retinitis while their CD4 counts were above 195 cells/microL.
      We also analysed, based on CD4 counts, 76 AIDS patients with newly diagnosed CMV
      retinitis whose CD4 lymphocyte enumerations were done in laboratories that
      maintained certification in a common external quality control programme.
      FINDINGS: 5-24 weeks before retinitis was diagnosed, all five patients had had
      absolute CD4 lymphocyte counts of less than 85 cells/microL, and 4-7 weeks before
      diagnosis, all five patients had started taking highly active antiretroviral
      treatment (HAART) regimens. Only one (4%) of 27 patients enrolled in the trial
      between July, 1995, and February, 1996, had an absolute CD4 count of more than 50
      cells/microL, and none of 27 had an absolute CD4 count of more than 100/microL on
      entry to the trial. However, from March, 1996 (when indinavir and ritonavir were
      approved by the FDA for marketing in the USA), to August, 1996, 14 (29%) of 49
      patients had CD4 counts of more than 50/microL and seven (14%) of 49 had a CD4
      count of more than 100 cells/microL on entry. INTERPRETATION: These findings
      suggest that the early immunological effects of HAART may not provide sufficient
      protection to prevent CMV retinitis in patients who have very low CD4 counts when
      therapy is started. Clinicians should note that CMV retinitis may now occur in
      patients who have CD4 counts of more than 100 cells/microL.

PMID- 9164320
TI  - Copper content in Areca catechu (betel nut) products and oral submucous fibrosis.

PMID- 9164321
TI  - Effect of low-molecular-weight heparin on serum potassium.

PMID- 9164323
TI  - Re-emergence of human monkeypox in Zaire in 1996. Monkeypox Epidemiologic Working
      Group.

PMID- 9164322
TI  - Enteroaggregative Escherichia coli in infant feeding bottles.

PMID- 9164324
TI  - Glutathione S-transferase theta 1 (GSTT1) gene defect in myelodysplasia and acute
      myeloid leukaemia.

PMID- 9164325
TI  - Glutathione S-transferase gene deletions in myelodysplasia.

PMID- 9164326
TI  - Apolipoprotein E genotype and cognition in the very old.

PMID- 9164327
TI  - Spread of HIV-1 to children in Cambodia.

PMID- 9164328
TI  - Pistachio-green stools and anaemia in infancy: early signs of cystic fibrosis?

PMID- 9164329
TI  - Getting the vaccine strategy right in HIV-1 disease.

PMID- 9164330
TI  - Makers of blood products settle US HIV suits.

PMID- 9164331
TI  - Aortic dissection.

PMID- 9164332
TI  - Occupational asthma.
AB  - Occupational asthma is a common disorder that may be caused by several hundred
      agents and has a variety of pathogenetic mechanisms. Level of exposure is an
      important risk factor, and reduction of exposure is the only certain method of
      prevention. Atopy and smoking are further risk factors for IgE-mediated asthma
      but have not been found to increase risk in forms of the disorder that have other
      mechanisms. The key to diagnosis is a low threshold of suspicion; several
      investigative procedures can be used to confirm the diagnosis. Many patients
      suffer from continued asthma despite cessation of exposure; early diagnosis and
      early removal from exposure are the most important factors for improving the long
      term outcome.

PMID- 9164334
TI  - Crap-trapping.

PMID- 9164333
TI  - Medicine, Durer, and the praying hands.

PMID- 9164335
TI  - Losartan versus captopril in elderly patients with heart failure.

PMID- 9164336
TI  - Losartan versus captopril in elderly patients with heart failure.

PMID- 9164337
TI  - Losartan versus captopril in elderly patients with heart failure.

PMID- 9164338
TI  - Losartan versus captopril in elderly patients with heart failure.

PMID- 9164339
TI  - Haemochromatosis Cys282Tyr mutation in pyridoxine-responsive sideroblastic
      anaemia.

PMID- 9164340
TI  - Antibiotic treatment in acute bacterial sinusitis.

PMID- 9164341
TI  - Antibiotic treatment in acute bacterial sinusitis.

PMID- 9164342
TI  - Occlusive paromomycin for cutaneous leishmaniasis.

PMID- 9164343
TI  - Familial intracranial aneurysms.

PMID- 9164344
TI  - Familial intracranial aneurysms.

PMID- 9164345
TI  - Drug interactions with zileuton.

PMID- 9164346
TI  - Lessons from antineoplaston.

PMID- 9164347
TI  - Lessons from antineoplaston.

PMID- 9164348
TI  - Lessons from antineoplaston.

PMID- 9164349
TI  - Lessons from antineoplaston.

PMID- 9164350
TI  - Health service changes in New Zealand.

PMID- 9164351
TI  - Legal aspects of dementia.

PMID- 9164352
TI  - Programmed bone-marrow donor for a leukaemic sibling, 10 years on.

PMID- 9164353
TI  - Transferring evidence from research into practice: 4. Overcoming barriers to
      application.

PMID- 9164354
TI  - Hepatocyte-specific contrast media for CT. An experimental investigation.
AB  - CT is an important technique in liver imaging. To improve the detection of focal
      liver lesions the use of non-specific, water-soluble contrast media (CM) is
      mandatory. However, even with use of these CM the sensitivity in tumour detection
      is low. In the development of liver-specific CM, the majority of the agents have
      been targeted to the reticuloendothelial system (RES). The clinical use of RES
      specific contrast agents has been hampered by frequent adverse reactions, and a
      new concept whereby the CM is taken up by the hepatocytes has been developed as
      an alternative. Such a CM is taken up by normal liver parenchyma but not by
      tumour cells, enhancing the difference between normal and pathological tissue,
      and therefore improving the diagnostic sensitivity. In the present investigation,
      FP 736-03 and FP 736-04, two hepatocyte-specific lipid emulsions, have been
      studied using animal models. In normal liver parenchyma dose-dependent
      enhancement was found, whereas in tumour tissue of experimental liver metastases
      and hepatocellular carcinoma, no enhancement was noted. The virtually unchanged
      attenuation in tumour tissue meant that the liver-to-lesion contrast increased
      steadily during the observation period. In an attempt to establish the
      relationship between enhancement and tumour detection, the accumulated doses of
      FP 736-04 were used. Increasing accuracy in the diagnosis of liver metastases was
      found up to an enhancement level of 30 HU. A further increase yielded similar
      detection rates, but a higher proportion of false-positive results. Comparison
      with iohexol was rendered difficult by the occurrence of image artefacts when
      this CM was used. However, FP 736-03 proved superior to both native and iohexol
      enhanced CT for detection of hepatic metastases. The efficacy of FP 736-04 was
      also studied in diseased hepatic parenchyma. In cases of fatty liver
      infiltration, enhancement by FP 736-04 was significantly reduced as compared with
      normal controls. The degree of enhancement observed in cirrhotic livers did not
      differ significantly from that in the controls. These preclinical investigations
      have shown that the hepatocyte-specific lipid emulsions FP 736-03 and FP 736-04
      improve the diagnostic accuracy of focal liver lesions as compared to native and
      water-soluble CM-enhanced CT. FP 736-04 is taken up by diseased liver parenchyma.
      However, the detection of malignancy in steatotic and cirrhotic livers has not
      yet been studied with use of this CM.

PMID- 9164355
TI  - New guidelines for diagnosis and management of asthma.

PMID- 9164356
TI  - Adverse effects of medications for rhinitis.
AB  - LEARNING OBJECTIVES: Reading this article will reinforce the reader's awareness
      of the adverse effects of medications used for the treatment of rhinitis. DATA
      SOURCES: Articles on therapy of rhinitis and reports of associated side effects
      were reviewed. A MEDLINE database using subject keywords was searched from 1992
      through 1997. STUDY SELECTION: Pertinent articles were chosen. A distinction was
      made in the text between controlled studies and case reports. RESULTS:
      Antihistamines, decongestants, anticholinergic agents, and corticosteroids, alone
      or in combination are used in the treatment of rhinitis. Reported side effects
      include sedation, psychosis, impaired learning and memory, and cardiac
      arrhythmias. CONCLUSION: Rhinitis and its complications are important medical
      conditions. Adverse reactions are often difficult to diagnose and assess. Side
      effects may arise from the use of individual drugs or from drug combinations.
      There is insufficient cause to abandon these medications, but physicians must be
      mindful of the inherent risks of the drugs that they prescribe and of others that
      their patients may be taking without the physicians' knowledge or approval.

PMID- 9164357
TI  - A wheezy infant unresponsive to bronchodilators.
AB  - When infants with recurrent wheezing have a clinical course inconsistent with
      asthma, an extensive list of alternative diagnoses needs to be considered.
      Anatomic malformations, such as congenital heart disease, laryngotracheomalacia,
      and diaphragmatic hernia, should be considered for immediate medical
      stabilization and early surgical correction. Life-threatening infections such as
      bacterial epiglottitis, retropharyngeal cellulitis, and viral myocarditis require
      prompt intervention. A careful history and physical examination reveal important
      diagnostic clues that, in this case, prompted a directed evaluation to rule out
      common masqueraders of asthma such as foreign body aspiration, cystic fibrosis,
      gastroesophageal reflux, viral pneumonitis, or pulmonary tuberculosis. On
      occasion, such a search is unrevealing and a diagnostic challenge remains. In
      those situations, judicious use of modern technology to scrutinize anatomic (high
      resolution computed tomography) and functional (infant pulmonary function tests)
      pathology, and justifiable invasive procedures such as bronchoscopy and lung
      biopsy, uncover the true diagnosis, allowing for optimal management.

PMID- 9164358
TI  - Salmeterol versus theophylline in the treatment of asthma.
AB  - BACKGROUND: Although theophylline is recommended by current guidelines for the
      management of asthma in patients with persistent symptoms, theophylline has a
      narrow therapeutic index, requiring individual dose titration and regular
      monitoring of serum theophylline concentrations to avoid adverse effects.
      OBJECTIVE: To compare the inhaled long-acting bronchodilator, salmeterol, with
      the oral bronchodilator, theophylline, in the maintenance treatment of asthma.
      METHODS: In two multicenter, randomized, double-blind, double-dummy, placebo
      controlled, parallel-group studies, patients received salmeterol aerosol 42
      micrograms, extended-release theophylline capsules, or placebo twice daily for 12
      weeks. RESULTS: Of 638 adult and adolescent patients with moderate asthma who
      entered the prebaseline theophylline titration period, 154 were withdrawn prior
      to randomization (71 due to theophylline-related adverse effects); 484 patients
      comprised the intent-to-treat population. The mean serum theophylline
      concentration measured approximately seven hours postdose during the titration
      period in the theophylline group was 12.7 mg/L (70 mumol/L). The same dose during
      the treatment period resulted in a mean serum theophylline concentration between
      7.6 to 7.9 mg/L (42-44 mumol/L) when measured approximately 12 hours postdose.
      Salmeterol was significantly more effective than theophylline or placebo in
      improving mean morning PEF over the entire 12 weeks (P < or = .02). Mean predose
      FEV1 improved significantly with salmeterol compared with placebo (P < .001);
      there was no difference between theophylline and placebo. Salmeterol was also
      significantly more effective than theophylline or placebo (P < .02) in improving
      asthma symptoms, reducing nighttime awakenings, and reducing the daily use of
      albuterol. After 12 weeks of treatment, patients in the salmeterol group
      expressed significantly greater overall satisfaction with their asthma medication
      than did patients who received theophylline (P < .01). Patients in the
      theophylline group experienced more gastrointestinal adverse events than did
      patients in the salmeterol group (P < .05). CONCLUSION: Salmeterol, 42 mg twice
      daily, was better tolerated and significantly more effective than extended
      release theophylline twice daily in the maintenance treatment of asthma.

PMID- 9164359
TI  - Inhibition of peripheral blood mononuclear cell proliferation by cardiac
      glycosides.
AB  - INTRODUCTION: Prior studies have shown that ouabain, a cardiac glycoside that
      inhibits the sodium, potassium adenosine triphosphatase (Na+,K+ ATPase) enzyme,
      downregulates phytohemagglutinin (PHA)-induced peripheral blood mononuclear cell
      (PBMNC) proliferation. OBJECTIVE: This study examined and compared the effects of
      both ouabain and digoxin, a cardiac glycoside used therapeutically in humans, on
      PBMNC proliferation. METHODS: Peripheral blood mononuclear cells were isolated
      from healthy human subjects, incubated for 72 hours with and without PHA (2%) in
      the presence and absence of ouabain (10(-12) M to 10(-4) M) or digoxin (10(-9) M
      to 10(-6) M), and pulsed with 3H thymidine. RESULTS: For PHA-stimulated PBMNCs in
      the ouabain-treated group (n = 10 subjects), the mean (+/-STD) % uptake (% 3H
      thymidine uptake in absence of ouabain) was 80.5 +/- 6.0 at 10(-12) M ouabain,
      73.1 +/- 8.4 at 10(-10) M, 47.89 +/- 13.1 at 10(-8) M, 6.9 +/- 3.2 at 10(-6) M,
      and 3.4 +/- 1.6 at 10(-4) M. For PHA-stimulated cells in the digoxin-treated
      group (n = 9 subjects), the mean (+/-STD) % uptake (% 3H thymidine uptake in
      absence of digoxin) was 89.8 +/- 9.8 at 10(-9) M digoxin, 92.6 +/- 8.2 at 10(-8)
      M, 54.3 +/- 19.8 at 10(-7) M, and 1.0 +/- 2.4 at 10(-6) M. Repeated measures
      ANOVA demonstrated a significant effect of concentration of both glycosides on
      PBMNC proliferation (P < .01). The inhibitory effect was reversible, but was
      largely abbrogated if ouabain was added after 48 hours of incubation with PHA.
      Further, the inhibitory effect extended to PBMNCs stimulated with recall antigen
      (tetanus) and to fractionated PBMNCs (CD4+, CD8+ and CD19+) stimulated with
      mitogens. Additionally, dose-response inhibitory effects of glycosides on PBMNC
      Na+,K+ ATPase enzyme activity and interleukin-2 (IL-2) secretion by PHA
      stimulated PBMNC were also noted. Neither glycoside had an effect on spontaneous
      PBMNC proliferation (no PHA) or trypan blue exclusion. CONCLUSIONS: These studies
      demonstrate that both cardiac glycosides inhibited PHA-induced PBMNC
      proliferation, possibly via Na+,K+ ATPase inhibition, but not via cell toxicity.
      The concentration range over which inhibition was observed was similar for both
      glycosides. The results raise the possibility that therapeutic or toxic doses of
      digoxin could have an effect on cell-mediated immunity in vivo.

PMID- 9164360
TI  - Risk assessment in determining systemic reactivity to honeybee stings in
      beekeepers.
AB  - BACKGROUND: The use of laboratory tests as a reliable method for risk assessment
      in determining the systemic reactivity of beekeepers to honeybee stings has
      proven unsatisfactory. OBJECTIVE: This study was conducted to evaluate the
      usefulness of a structured questionnaire as a supplement to bee venom-specific
      IgE data in the prediction of systemic sting reactions of 78 beekeepers to
      honeybee stings. METHODS: Participants in previous studies completed a
      questionnaire concerning potential risk factors of systemic sting reactions.
      Serum bee venom IgE was measured by CAP-RAST. Skin prick tests were performed
      with standardized bee venom extracts prior to the beekeeping season. Venom
      challenges were performed using unintentional field stings. A new questionnaire
      concerning sting reactions during the recent beekeeping season was sent to the
      beekeepers after it had ended. A multiple logistic regression analysis was done
      to evaluate the influence of potential risk factors upon systemic bee sting
      reactions. RESULTS: Four variables were significant. The pre-season presence of
      serum bee venom-specific IgE at concentrations exceeding 1.0 kU/L increased the
      risk of systemic reactions 12-fold. The risk was 10-fold if nasal or respiratory
      symptoms had occurred while working at hives. When the years spent in beekeeping
      were fewer than eight the risk of systemic sting reaction was 9-fold, any
      previous systemic reaction increased the risk 8-fold. CONCLUSION: The use of more
      detailed patient histories in combination with laboratory tests may markedly
      improve the reliability of risk assessment.

PMID- 9164362
TI  - Ipratropium nasal spray in children with perennial rhinitis.
AB  - OBJECTIVE: To compare the efficacy and safety of ipratropium nasal spray and
      placebo administered twice each day for 4 weeks in pediatric patients with
      perennial rhinitis who had rhinorrhea as a major complaint. METHODS: This was a
      multicenter, double-blind, parallel group study. Patients aged 6 to 18 years with
      symptoms of perennial nonallergic (PNAR) or perennial allergic rhinitis (PAR)
      were randomized to receive ipratropium (42 micrograms per nostril) or placebo
      nasal spray, double-blind, twice each day for 4 weeks. Efficacy was evaluated by
      nasal symptoms, especially anterior rhinorrhea, and quality of life. Previous
      caregivers for rhinitis and medications used in the past were also evaluated.
      RESULTS: A total of 202 patients were empanelled, 162 with PAR, 40 with PNAR; of
      these 151 with mild-severe rhinorrhea were evaluated for efficacy. Treatment with
      ipratropium reduced symptoms of rhinorrhea primarily in patients with PNAR. In
      patients with PAR this response was less pronounced, and was seen as a modest
      decrease in the severity of rhinorrhea noted in the first 2 weeks of treatment.
      Quality of life assessments confirmed that rhinorrhea was bothersome to these
      pediatric patients, and suggested that treatment with ipratropium nasal spray was
      associated with an improvement, especially in the patients with PNAR. There were
      few adverse events; these were similar in the two treatment groups. CONCLUSIONS:
      Ipratropium nasal spray 0.03% administered at a dose of 42 micrograms/nostril bid
      is a safe and effective new therapy for control of anterior rhinorrhea in
      pediatric patients with PNAR. Twice daily administration is adequate for patients
      with PNAR, but patients with PAR might benefit from more frequent administration
      (e.g., tid).

PMID- 9164361
TI  - Fluticasone propionate aqueous nasal spray treatment for perennial allergic
      rhinitis in children.
AB  - BACKGROUND: Topical corticosteroid is now accepted as safe and most effective in
      controlling all symptoms of both allergic and nonallergic rhinitis. Fluticasone
      propionate aqueous nasal spray is a new once daily topical corticosteroid
      preparation. OBJECTIVE: To evaluate the efficacy and safety of fluticasone
      propionate in children 5 to 11 years of age with perennial allergic rhinitis.
      METHOD: A double-blind, placebo-controlled, parallel group of 127 recruited
      patients of whom 106 were evaluated. Treatment with once daily fluticasone
      propionate 100 micrograms or placebo for 4 weeks followed by a 2-week followup
      period. Fifty-three patients of each group were treated with fluticasone
      propionate or placebo by randomized assignment. RESULTS: There was no statistical
      significance of the sex, mean age, weight, and height of the two groups. Patients
      treated with fluticasone propionate showed a significant decrease in total
      symptom scores rated by physicians at 2 weeks and 4 weeks, respectively (P < .01,
      P < .05). The rhinitis symptom scores in treatment group rated by patients (nasal
      blockage, sneezing, rhinorrhea) were significantly decreased at 2 weeks (P < .05,
      P < .01). Nasal symptoms as assessed by doctors (turbinate swelling, color of
      nasal mucosa, secretion, and postnasal drip) also decreased at 2 and 4 weeks, but
      were not statistically significant, except for the secretion at 2 weeks and
      postnasal drip at 4 weeks (P < .05). There was no evidence of effects on adrenal
      function by morning plasma cortisol concentration between the two groups.
      CONCLUSION: Fluticasone propionate was safe and effective in children aged 5 to
      11 years with perennial allergic rhinitis.

PMID- 9164363
TI  - Urinary N-methylhistamine in asthmatic children receiving azelastine
      hydrochloride.
AB  - BACKGROUND: Histamine has a particular role in the pathogenesis of bronchial
      asthma, and many antiallergic drugs have been developed with antihistaminic
      action in mind. Recently, a sensitive and specific assay for measuring histamine
      and its metabolites has been developed. There are, however, no reports of the
      effect of antiallergic drugs on histamine levels in asthmatic patients.
      OBJECTIVES: To determine the relationship between clinical symptoms and histamine
      levels in asthmatic patients receiving an antiallergic agent. METHODS: A
      prospective study was designed in asthmatic children treated with azelastine
      hydrochloride. The evaluation of clinical symptoms was based on scores of the
      severity of exacerbations, activities of daily living, quality of sleep, and
      required therapy. Urinary excretion of N-methylhistamine, a major metabolite of
      histamine, was measured by double antibody radioimmunoassay. RESULTS: In the
      patients treated with azelastine, the improvement in clinical symptoms of
      bronchial asthma correlated significantly with a decrease in urinary N
      methylhistamine excretion (r2 = 0.434, P < .001), while no such relationship was
      noted in patients receiving no antiallergic agent. Urinary N-methylhistamine
      excretion showed no diurnal change or influence of meals. CONCLUSIONS: Decreased
      urinary N-methylhistamine excretion may be a direct reflection of the
      antihistaminic action of azelastine in vivo. Measurement of urinary N
      methylhistamine excretion can be used to evaluate the efficacy of agents with
      antihistaminic action in the treatment of bronchial asthma.

PMID- 9164364
TI  - Glucocorticosteroids inhibit leukotriene production.
AB  - BACKGROUND: The mode of action of corticosteroids, important drugs in the
      treatment of inflammatory disease, is not yet fully understood. Corticosteroids
      are known to inhibit phospholipase A2 in unprimed eosinophils and basophils,
      preventing leukotriene synthesis, but their effect on cells that are already
      primed is unknown. OBJECTIVE: As inflammatory cells from atopic subjects are
      often primed in vivo, we studied the effects of two potent corticosteroids on
      basophil sulfidoleukotriene production in peripheral blood mixed leukocytes
      (PBML) from in-season and out-of-season atopic individuals. METHODS: Cells were
      incubated for 24 hours with mometasone furoate or beclomethasone dipropionate,
      primed with IL-3, stimulated with calcium ionophore, buffer, allergen or anti
      IgE, and leukotriene production was quantified. RESULTS: Peripheral blood
      mononuclear leukocytes from five of ten donors (in season) produced elevated
      sulfidoleukotrienes without a stimulus; cells from seven donors responded to anti
      IgE by increased sulfidoleukotrienes. Neither steroid consistently affected
      sulfidoleukotriene production in anti-IgE-stimulated cells which were releasing
      sulfidoleukotrienes in the absence of a stimulant. In comparison,
      sulfidoleukotriene production was significantly reduced by 0.01 to 10 nM
      beclomethasone dipropionate or mometasone furoate when the cells were primed with
      IL-3 after exposure to the drug and stimulated with calcium ionophore or
      allergen, but no dose-relationship was apparent. Leukotriene production by PBML
      in response to anti-IgE was potently inhibited by all concentrations of
      mometasone furoate (0.01 nM to 1 microM) with an inhibitory concentration50 of
      less than 0.01 nM. Beclomethasone dipropionate inhibited sulfidoleukotriene
      production in this group (inhibitory concentration50 6 nM) in a dose-dependent
      manner. CONCLUSIONS: Sulfidoleukotriene production and, conceivably, priming may
      be more effectively inhibited by mometasone furoate than beclomethasone
      dipropionate.

PMID- 9164366
TI  - Transfer of atopy following bone marrow transplantation.
AB  - BACKGROUND: Bone marrow transplantation is an optimal treatment of acute leukemia
      and aplastic anemia. Allergic manifestations in recipients long after bone marrow
      transplantation have been reported. A case involving transfer of atopy manifested
      as food allergy-induced-atopic dermatitis is reported. METHODS: The donor and the
      patient were investigated by prick tests and RAST to the same food allergens.
      Single blind, oral challenge to egg documented food allergy in the recipient.
      RESULTS: A 5-year-old boy without history of atopy developed severe atopic
      dermatitis after bone marrow transplantation from his HLA-identical sister for
      acute lymphoblastic leukemia. The patient's course had been marked previously by
      acute graft versus host disease and cytomegalovirus infection. Immunoallergic
      evaluation showed an exquisite sensitization to egg, peanut, and soybean. Total
      IgE was 6400 KIU/L. Concomitantly, the donor showed the same sensitizations.
      Absolute avoidance resulted in the regression of atopic dermatitis. Subsequently,
      new sensitization to wheat flour, Dermatophagoides pteronyssinus, birch, and
      plantain pollens was detected. The donor developed asthma. CONCLUSIONS: This case
      gives evidence of the transfer of sensitization from donor to recipient. The
      passive transfer of memory cells within the bone marrow inoculum is a possible
      mechanism. The current concept of allergy supports down regulation of Th1 cells
      to the benefit of Th2 cells. Additional deregulation induced by acute graft
      versus host disease, cytomegalovirus infection, and immunosuppression is
      possible.

PMID- 9164365
TI  - Continuous avoidance measures with or without acaricide in dust mite-allergic
      asthmatic children.
AB  - BACKGROUND: Improvement in the quality of life in the Western world and increased
      time spent indoors by children have enhanced the spread of house dust mites and
      increased the exposure time for sensitive children. Also, exposure to house dust
      mites in infancy and subsequent development of childhood asthma have been
      clinically linked. Recently, new acaricides have been developed. OBJECTIVE: To
      test the efficacy of the new acaricide (esdepallethin and piperonyl butoxide-
      "Acardust") combined with environmental control compared with continuous house
      dust mite avoidance measures. METHOD: Forty-six house dust mite-allergic,
      asthmatic children were evaluated for 6 months in a prospective, randomized,
      double-blind, and placebo-controlled study. Patients were randomly allocated to
      active and placebo acaricide treatment combined with avoidance measures, whereas
      only continuous avoidance measures were taken in the third group. Symptom score,
      medication usage, and peak flow measurements were recorded daily. The amount of
      house dust mite allergen in the dust vacuumed from the bedrooms was also
      measured. RESULTS: Morning and evening peak expiratory flow rates and forced
      expiratory volume in one second remained unchanged throughout the study period.
      In all groups, the symptom scores improved significantly, whereas the amount of
      house dust mite allergen decreased significantly at the end of the trial.
      CONCLUSIONS: Continuous house dust mite avoidance measures have a significant
      positive effect on the symptomology of children with mild or moderate asthma.
      "Acardust" combined with continuous house dust mite avoidance measures is not
      more effective than continuous house dust mite avoidance measures alone in the
      treatment of house dust mite-allergic, asthmatic children.

PMID- 9164367
TI  - Unbalanced production of interleukin-5 and interleukin-2 in children with atopic
      dermatitis.
AB  - BACKGROUND: Cytokines, such as interleukin (IL)-5, produced by T helper type 2
      Th2) cells appear to play an important role in the inflammatory processes
      associated with atopic dermatitis. The roles of cytokines produced by Th1 cells
      remain controversial. OBJECTIVE: We examined IL-5 and IL-2 mRNA abundance in and
      protein production by peripheral blood mononuclear cells (PBMCs) from patients
      with atopic dermatitis and compared those from controls. METHODS: Peripheral
      blood mononuclear cells were isolated from six children with atopic dermatitis
      and six control children, and stimulated with both phytohemaggulutinin (PHA) and
      phorbol 12-myristate 13-acetate (PMA). The abundance of IL-5 and IL-2 mRNA in
      PBMCs was measured by reverse transcription-polymerase chain reaction analysis.
      The production of IL-5 and IL-2 by PBMCs was also determined by enzyme-linked
      immunosorbent assay. RESULTS: After incubation with PHA and PMA, PBMCs from
      atopic children showed significantly higher IL-5 mRNA abundance (P < .05) and IL
      5 production (P < .01), as well as a lower amount of IL-2 mRNA (P = .056) and IL
      2 production (P < .05) than those from healthy controls. The time course of
      changes in IL-5 mRNA abundance induced by PHA and PMA in PBMCs from atopic
      children differed markedly from that observed with healthy controls, whereas the
      time course of changes in IL-2 mRNA abundance were similar between the two
      groups. CONCLUSIONS: The increased IL-5 and decreased IL-2 production observed
      with PBMCs from children with atopic dermatitis may underlie the activation of
      eosinophils and high serum immunoglobulin E concentrations also apparent in such
      individuals. An imbalance in the number and activity of Th1 and Th2 cells is
      likely to be responsible for the abnormal pattern of cytokine production in
      atopic dermatitis.

PMID- 9164369
TI  - Choosing a skin test device.

PMID- 9164370
TI  - Who knows how to use a metered dose inhaler?

PMID- 9164371
TI  - Subclinical thyroid dysfunction.
AB  - Subclinical thyroid dysfunction may be defined as an abnormal serum thyrotropin
      concentration in an asymptomatic patient with a normal serum free thyroxine
      concentration. This article addresses the prevalence, natural history, and
      potential pathophysiological consequences of subclinical hypothyroidism and
      subclinical thyrotoxicosis. Subclinical hypothyroidism, which occurs in more than
      10% of women older than 60 years, may be accompanied by an unfavorable serum
      lipid profile and may lower the threshold for the development of major depressive
      disorder. Subclinical thyrotoxicosis, which is most commonly due to thyrotropin
      suppressive levothyroxine sodium therapy, may be associated with reduced bone
      mineral density in postmenopausal women and confers a 3-fold relative risk for
      the development of atrial fibrillation. While there are no outcome data to
      support therapeutic intervention in subclinical thyroid dysfunction, some
      screening and management recommendations are offered.

PMID- 9164372
TI  - Hemodynamic changes after cardioversion of chronic atrial fibrillation.
AB  - After cardioversion of chronic atrial fibrillation to sinus rhythm, there is a
      gradual increase of 56% in cardiac output over 4 weeks. The increase is caused by
      the gradual return and increasing strength of left atrial mechanical activity as
      the atrial myopathy of chronic atrial fibrillation subsides. Cardiac output
      decreases after cardioversion of atrial fibrillation in more than a third of
      patients, and the decrease may last a week. Acute pulmonary edema is uncommon;
      50% of cases occur within 3 hours of cardioversion, with a mortality of 18%. The
      reduced cardiac performance after cardioversion most likely results from the
      combination of heart disease and cardiac depressant effects of anesthetic drugs
      used. Pulmonary and/or coronary artery emboli and the resumption of right atrial
      mechanical activity before left atrial mechanical activity may be additional
      factors in the pathogenesis of pulmonary edema after cardioversion. Anticoagulant
      therapy should be continued for a month or longer after cardioversion in those
      patients who maintain sinus rhythm to prevent thromboembolism.

PMID- 9164373
TI  - The use of D-dimer testing and impedance plethysmographic examination in patients
      with clinical indications of deep vein thrombosis.
AB  - OBJECTIVE: To prospectively test the hypothesis that a diagnosis of deep vein
      thrombosis can be excluded in outpatients who present with clinical indications
      of deep vein thrombosis and whose results of D-dimer testing and impedance
      plethysmographic examination on the day of presentation are normal. DESIGN:
      Prospective cohort study. SETTING: Four university-affiliated hospitals. METHODS:
      Three hundred ninety-eight consecutive patients with clinical indications of deep
      vein thrombosis were included in the final analysis. All patients underwent an
      assessment of pretest probability, bedside D-dimer testing, and impedance
      plethysmographic examination. In most patients, if the results of D-dimer testing
      and impedance plethysmographic examination were negative for deep vein
      thrombosis, anticoagulants were withheld and patients were followed up for 3
      months. If the results of one or both tests were abnormal, an examination using
      venous compression ultrasonography or phlebography was performed. RESULTS: In the
      majority of patients (69%), the results of D-dimer testing and impedance
      plethysmographic examination were normal. This combination had a negative
      predictive value of 98.5% (95% confidence interval, 96.3-99.6) for deep vein
      thrombosis. CONCLUSION: The results of the D-dimer assay and impedance
      plethysmographic examination on the day of presentation can be used to treat the
      majority of outpatients who present with clinical indications of deep vein
      thrombosis without further testing.

PMID- 9164374
TI  - An evaluation of a chest pain diagnostic protocol to exclude acute cardiac
      ischemia in the emergency department.
AB  - BACKGROUND: Although accelerated diagnostic protocols are being increasingly used
      in emergency departments to diagnose acute cardiac ischemia, there have been no
      prospective evaluations of a chest pain diagnostic protocol with serial
      determinations of creatine kinase MB isoenzyme and mandatory exercise
      electrocardiography (ExECG). METHODS: Prospective cross-sectional study in which
      chest pain protocol results were compared with final (reference) diagnoses of
      acute cardiac ischemia (including acute myocardial infarction and unstable
      angina). Patients in need of hospital admission but at low probability (by a
      validated algorithm) for acute myocardial infarction were examined for
      exclusions: known coronary artery disease, cardiac complications, severe
      comorbidities, or inability to perform exercise testing. A 12-hour diagnostic
      protocol included serial measurements of creatine kinase MB, ECG, and clinical
      assessments followed by ExECG for those with negative initial serial testing.
      Reference diagnoses were established during hospitalization and diagnostic
      accuracy was assessed. RESULTS: The study group of 317 patients was 54% male and
      65% black, and had a mean age of 46.6 years; 9.5% had a final diagnosis of acute
      cardiac ischemia. For this diagnosis, the protocol had a sensitivity of 90.0%
      (95% confidence interval, 72.3%-97.4%); specificity, 50.5% (95% confidence
      interval, 44.6%-56.4%); positive predictive value, 16.0%; and negative predictive
      value, 98.0%. Creatine kinase MB, serial ECGs, and ExECG each made a contribution
      to improved sensitivity and accuracy, whereas clinical reassessments were less
      discriminating, as indicated by protocol's receiver operating characteristic
      curve. CONCLUSIONS: A chest pain diagnostic protocol achieved high sensitivity
      and improved specificity over the standard emergency department workup. There
      were no adverse advents associated with early ExECG.

PMID- 9164375
TI  - Victimization among substance-abusing women. Worse health outcomes.
AB  - BACKGROUND: Although women with a history of victimization are known to have
      increased somatic symptoms, health care utilization, and substance abuse, the
      health effects of victimization on substance-abusing women are uncertain.
      OBJECTIVE: To examine whether a history of victimization among substance-abusing
      women is associated with more medical problems or emergency department visits.
      METHODS: Interview data were collected from 2322 women seeking publicly funded
      addiction treatment from September 1992 to January 1996. We compared women with a
      lifetime history of physical or sexual abuse with those without such a history by
      bivariate and multivariable analyses. Variables included episodic medical
      disease, chronic medical disease, recent emergency department visits, substance
      abuse characteristics, and demographic data. RESULTS: The prevalence of
      victimization was 42%. In bivariate analyses, the following variables had
      significant association with victimization histories: episodic medical disease,
      recent emergency department visit, chronic medical disease, primary care
      physician's awareness of substance abuse history, ethnicity, and lower income.
      Alcohol and crack cocaine users had higher prevalence of victimization compared
      with heroin or noncrack cocaine users (P = .001). In the logistic regression, the
      following variables remained independently and significantly associated with
      victimization: episodic medical disease (odds ratio [OR], 2.15; 95% confidence
      interval [CI], 1.70-2.73), physician awareness of substance abuse (OR, 1.78; 95%
      CI, 1.42-2.23), emergency department visit (OR, 1.57; 95% CI, 1.22-2.03), chronic
      medical disease (OR, 1.51; 95% CI, 1.19-1.92), and lower income. CONCLUSION:
      Victimization in urban, poor, substance-abusing women is associated with more
      medical disease and health care utilization. Interventions that focus on the
      interconnected problems these women face may more effectively affect this
      challenging population.

PMID- 9164376
TI  - Heart failure treatment with angiotensin-converting enzyme inhibitors in
      hospitalized Medicare patients in 10 large states. The Large State Peer Review
      Organization Consortium.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors have been proved to
      reduce mortality, rates of hospitalization, and disease progression in patients
      with heart failure. Investigators have suggested that ACE inhibitors are
      underused in heart failure. METHODS: We examined the use of ACE inhibitors and
      the documentation of cardiac ejection fractions (EFs) in Medicare patients
      admitted to acute care hospitals with a principal diagnosis of heart failure. A
      random sample of at least 600 medical records in each of 10 populous states was
      retrospectively abstracted by peer review organizations. A total of 6749 records
      were reviewed of patients aged 65 years and older who were discharged in 1993 and
      1994. The review tool was adapted from the Heart Failure Guidelines disseminated
      by the Agency for Health Care Policy and Research. An ideal candidate cohort was
      created of patients most likely to benefit from ACE inhibitors on the basis of
      their EF values (< 40%), renal function, absence of hyperkalemia, and absence of
      other contraindications. RESULTS: Fifty-five percent (95% confidence interval,
      54%-56%) of patients received ACE inhibitors at discharge. In the ideal candidate
      group, 73% (95% confidence interval, 71%-75%) of patients received ACE inhibitors
      at discharge. The oldest group was least likely to have ACE inhibitors prescribed
      at discharge. The EF was documented in 59% (95% confidence interval, 58%-60%) of
      records. CONCLUSIONS: Medicare chart review suggests under-use of ACE inhibitors
      in up to one quarter of patients who have no clear contraindications. A
      substantial number of patients without documented EF are also likely to benefit
      from the use of ACE inhibitors.

PMID- 9164378
TI  - The cost-effectiveness of preventing tuberculosis in physicians using tuberculin
      skin testing or a hypothetical vaccine.
AB  - BACKGROUND: Tuberculin skin testing using the purified protein derivative is
      recommended as part of a tuberculosis control program for health care workers.
      However, compliance with skin testing programs has been poor and their cost
      effectiveness is unknown. METHODS: A Markov-based decision analysis was performed
      to determine the cost-effectiveness of tuberculin skin testing over the entire
      lifetimes of physicians who are now in medical school. Assumptions were
      deliberately chosen to present a conservative estimate of cost-effectiveness.
      Indirect costs were not included. RESULTS: Annual testing cost $29,000 per life
      year saved and $39,000 per case of pulmonary tuberculosis prevented. In contrast,
      particulate respirators have been shown to cost millions of dollars per case
      prevented. Skin testing every 6 months was cost-effective in a subpopulation at
      high risk of infection (> or = 1.8-fold). During their entire lifetimes,
      physicians now in medical school can expect to avert 137 cases of pulmonary
      tuberculosis, prevent 7 tuberculosis deaths, and save 182 life-years because of
      skin testing programs. Improved compliance with annual skin testing and
      prophylactic isoniazid could more than triple this benefit. If available, a
      moderately effective vaccine would be even more cost-effective than tuberculin
      skin testing programs. CONCLUSIONS: Tuberculin skin testing is cost-effective and
      should be an integral part of any tuberculosis control program. Vaccination may
      one day be a feasible and cost-effective alternative to skin testing programs.

PMID- 9164377
TI  - Treating depressed primary care patients improves their physical, mental, and
      social functioning.
AB  - BACKGROUND: This study describes the functioning of primary care patients with
      major depressive disorder, the relationship of medical comorbidity to functional
      status, and the effects of depression-specific treatment on functional status
      after 8 months. METHODS: Patients were randomized to a protocol intervention
      (nortriptyline hydrochloride or interpersonal psychotherapy) or to usual care
      with the patient's physician in a clinical trial of primary care treatments of
      depression. Their functional status was evaluated using the Medical Outcomes
      Study 36-Item Short Form Health Survey (SF-36) and the Global Assessment Scale.
      Medical comorbidity was assessed with the Duke Severity of Illness Checklist. The
      Hamilton Rating Scale for Depression and Beck Depression Inventory were used to
      measure depressive severity. Assessments were conducted at baseline and at 1, 2,
      4, and 8 months after randomization. RESULTS: At baseline, patients reported
      substantial impairments in the functional domains as assessed by the SF-36 and
      Global Assessment Scale. Severity of general medical illness and depression were
      not correlated. Greater medical comorbidity was associated with diminished
      physical, but not psychological, functioning. Mean scores on SF-36 scales and the
      Global Assessment Scale improved significantly during the 8 months of follow-up.
      Patients assigned to protocol treatments showed greater improvement, compared
      with those assigned to usual care, on the SF-36 mental summary scale and most
      individual scales but not on the SF-36 physical summary scale. However, patients
      who completed protocol treatment also experienced significant improvement on the
      physical summary scale. Medical comorbidity was only a weak predictor of outcome.
      CONCLUSIONS: Primary care patients with major depressive disorder report
      substantial impairments in physical, psychological, and social functioning on
      initial assessment. Severity of baseline medical comorbidity did not correlate
      with severity of depression and only weakly correlated with functional status at
      8 months. Functional impairments improve with time, but standardized depression
      specific treatment is associated with greater improvement in more domains of
      functioning than is a physician's usual care.

PMID- 9164379
TI  - Effect of a vancomycin restriction policy on ordering practices during an
      outbreak of vancomycin-resistant Enterococcus faecium.
AB  - BACKGROUND: With the development of nosocomial pathogens that are resistant to
      multiple antimicrobial agents, reasonable restriction of antibiotic use has
      become a priority. METHODS: During an outbreak of vancomycin-resistant
      enterococcal infections, an audit of vancomycin hydrochloride use was conducted
      during October 3 through 21, 1994, and January 24 through February 2, 1995.
      During these periods, all orders for vancomycin were reviewed by clinical
      pharmacists. Use was classified as either appropriate or inappropriate based on
      recommendations by the Hospital Infection Control Practice Advisory Committee
      (HICPAC) of the Centers for Disease Control and Prevention, Atlanta, Ga. A policy
      restricting the use of vancomycin was adopted in November 1994. RESULTS: During
      the first audit in October 1994, 61% of vancomycin orders were considered
      inappropriate according to HICPAC criteria. At the time of this audit, the first
      cases of an outbreak of nosocomial vancomycin-resistant Enterococcus faecium had
      been detected. The follow-up audit showed that 30% of vancomycin orders were
      inappropriate by HICPAC criteria (P < .001). Overall use of vancomycin decreased
      by 50% and remained at this lower level for the following year. CONCLUSION: The
      institution of a vancomycin restriction policy was associated with a reduction of
      both inappropriate drug orders and total use.

PMID- 9164380
TI  - Screening and Barrett's esophagus.

PMID- 9164381
TI  - Homeopathy--the emperor's medicine.

PMID- 9164382
TI  - Atypical lymphocytes in acute malaria.

PMID- 9164383
TI  - Physicians' role in care of loved ones.

PMID- 9164384
TI  - The great divide.

PMID- 9164385
TI  - Cutting tobacco taxes, endangering youth.

PMID- 9164386
TI  - CMPA fees.

PMID- 9164387
TI  - CMPA fees.

PMID- 9164388
TI  - Sleep statement for adults only.

PMID- 9164389
TI  - Radical mastectomy now outdated.

PMID- 9164390
TI  - Introducing students to community health.

PMID- 9164391
TI  - Keeping cash flowing.

PMID- 9164392
TI  - Back to the grind and back on your feet.

PMID- 9164393
TI  - Publish or perish.

PMID- 9164394
TI  - Action long overdue on drug labelling.

PMID- 9164395
TI  - Entering medical school means pursuing all options.

PMID- 9164396
TI  - Alcohol, tobacco and cannabis use among Nova Scotia adolescents: implications for
      prevention and harm reduction.
AB  - OBJECTIVE: To characterize adolescent drug use in terms of a risk continuum and
      to explore the rationale for harm reduction as a potential approach for school
      based drug prevention. DESIGN: Self-reported surveys, in 1991 and 1996, of
      adolescent students concerning their use of drugs, especially alcohol, tobacco
      and cannabis, and the harmful consequences of such use. SETTING: Nova Scotia.
      PARTICIPANTS: A total of 3452 (in 1991) and 3790 (in 1996) junior and high school
      students in randomly selected classes in the public school system. OUTCOME
      MEASURES: Prevalence of drug use and patterns of multiple drug use and of alcohol
      and drug-related problems; independent risk factors for multiple drug use. The
      risk continuum for the response to alcohol problems was used as a policy
      framework. RESULTS: The prevalence of cigarette smoking and the use of
      hallucinogens and stimulants was markedly higher in 1996 than in 1991. Over one
      fifth (21.9%) of the students reported multiple drug use of alcohol and tobacco
      and cannabis in the 12 months before the 1996 survey. The 3 main subgroups-
      nonusers, users of alcohol only and users of multiple drugs--had distinct
      patterns of use, numbers of problems and risk factors. In all, 27.1% of the
      students had experienced at least 1 alcohol-related problem and 6% had
      experienced at least 1 drug-related problem in the 12 months before the 1996
      survey. CONCLUSION: There is a need for integrated school- and community-based
      drug prevention programs, with goals, strategies and outcome measures capturing
      the full spectrum of patterns of use and levels of risk among subgroups of the
      adolescent student population.

PMID- 9164397
TI  - Reducing the harm of adolescent substance use.

PMID- 9164398
TI  - The Krever inquiry: time to drop the appeals.

PMID- 9164399
TI  - Bioethics for clinicians: 11. Euthanasia and assisted suicide.
AB  - Euthanasia and assisted suicide involve taking deliberate action to end or assist
      in ending the life of another person on compassionate grounds. There is
      considerable disagreement about the acceptability of these acts and about whether
      they are ethically distinct from decisions to forgo life-sustaining treatment.
      Euthanasia and assisted suicide are punishable offences under Canadian criminal
      law, despite increasing public pressure for a more permissive policy. Some
      Canadian physicians would be willing to practise euthanasia and assisted suicide
      if these acts were legal. In practice, physicians must differentiate between
      respecting competent decisions to forgo treatment, providing appropriate
      palliative care, and acceeding to a request for euthanasia or assisted suicide.
      Physicians who believe that euthanasia and assisted suicide should be legally
      accepted in Canada should pursue their convictions only through legal and
      democratic means.

PMID- 9164400
TI  - A guide to interpreting discordant systematic reviews.
AB  - Systematic reviews are becoming prominent tools to guide health care decisions.
      As the number of published systematic reviews increases, it is common to find
      more than 1 systematic review addressing the same or a very similar therapeutic
      question. Despite the promise for systematic reviews to resolve conflicting
      results of primary studies, conflicts among reviews are now emerging. Such
      conflicts produce difficulties for decision-makers (including clinicians, policy
      makers, researchers and patients) who rely on these reviews to help them make
      choices among alternative interventions when experts and the results of trials
      disagree. The authors provide an adjunct decision tool--a decision algorithm--to
      help decision-makers select from among discordant reviews.

PMID- 9164401
TI  - Faculty development in Canadian medical schools: a 10-year update.
AB  - OBJECTIVE: To compare the current status of faculty development practices in
      Canadian medical schools with the status of such practices in 1986. DESIGN: Mail
      survey. SETTING: All 16 Canadian medical schools. PARTICIPANTS: Faculty
      development coordinators at the medical schools. OUTCOME MEASURES: Existence of
      faculty development committees, funding for faculty development activities, types
      of activities and recognition of faculty participation in such activities.
      RESULTS: Completed responses were received from all schools. They indicated a
      significant, positive evolution in faculty development since the previous survey,
      conducted in 1986. Most schools have established a faculty development committee
      and provide funds for such activities as workshops, sabbatical leaves and
      conference attendance. Although traditional development practices are prevalent,
      there is now widespread emphasis on computer technology, information retrieval,
      management skills and research. Experienced faculty and other experts are more
      widely used for consultation on teaching. Very little has been done to evaluate
      the impact of faculty development. CONCLUSION: Faculty development in Canadian
      medical schools has undergone a major, positive transition during the last 10
      years.

PMID- 9164402
TI  - Calling the boys home.

PMID- 9164404
TI  - Promises, promises.
AB  - As the federal election nears, Charlotte Gray looks at the role health care will
      play during the brief campaign. Reading through the campaign literature, she
      found that all parties are making similar statements. However, there are striking
      differences in the way they intend to preserve the health care system.

PMID- 9164403
TI  - Hepatitis C.

PMID- 9164405
TI  - Health care as an election issue: Alberta's experience.

PMID- 9164406
TI  - In Hong Kong, smokers are butting out in record numbers.
AB  - Thanks to a partial ban on tobacco advertising and a concerted effort by
      antismoking advocates and hospitals, more than 100,000 people have quit smoking
      in Hong Kong in the last 3 years, giving the British territory one of the world's
      lowest smoking rates. This article examines initiatives behind the successful
      trend and identifies how Hong Kong is addressing the challenge of reducing
      smoking rates among youth, women and poor people.

PMID- 9164407
TI  - Multiculturalism and AIDS: different communities mean different educational
      messages required.
AB  - Having a multitude of different ethnic communities forces Canada's AIDS educators
      to use many different methods to deliver their messages. These range from an AIDS
      bingo game that has been used to educate natives in northern Manitoba to attempts
      to take AIDS education to the streets of Toronto. With AIDS education, reports
      Olga Lechky, one message definitely does not fit all.

PMID- 9164408
TI  - Innovations making CME more clinically relevant, attractive.
AB  - Educators are rising to the challenge of making continuing medical education
      relevant, valuable and enjoyable for physicians. Lectures are being replaced by
      small-group, interactive sessions that try to ensure physicians come away with
      clinically relevant information that will affect daily practice. Community-based
      programs also allow physicians to fit learning into their busy lifestyles.

PMID- 9164409
TI  - The health risks of new-wave vegetarianism.
AB  - Many young people call themselves vegetarians because they don't eat meat, but
      the eating style they are adopting is fraught with health risks. In this article,
      which won CMAJ's 1996 Army Chouinard Memorial Essay Contest for Canadian
      journalism students, Laura Brydges Szabo looks at the "new vegetarianism" and the
      recommendations health care professionals are making to young people intent on
      following this incomplete diet. The contest encourages journalism students to
      write on health care topics.

PMID- 9164410
TI  - Evidence-based medicine designed to save physicians time, energy, FPS told.
AB  - Although not all physicians welcome the current move toward evidence-based
      medicine, Dr. Warren McIsaac, a member of the Institute for Clinical Evaluative
      Sciences in Ontario, says it is designed to save them time and energy. He made
      the comments during a meeting of family physicians in Ontario.

PMID- 9164411
TI  - Confusion surrounding repetitive strain injury highlighted at conference.
AB  - Uncertainty about disorders that account for many of the claims related to job
      injury at work became clear during a recent meeting, when speakers referred to
      the same disorders by several different names, including repetitive strain
      injury. Speakers discussed different types of injuries and reasons why they
      appear to be coming more common.

PMID- 9164412
TI  - Steroid therapy and H2-receptor antagonists: pharmacoeconomic implications.

PMID- 9164413
TI  - Genotyping of N-acetylation polymorphism and correlation with procainamide
      metabolism.
AB  - We studied the genotypes of polymorphic N-acetyltransferase (NAT2) in 145
      Japanese subjects by the polymerase chain reaction-restriction fragment length
      polymorphism method. The rapid-type NAT2*4 was expressed at a higher frequency
      (68.6%) than the slow-type genes with specific point mutations (NAT2*6A, 19.3%;
      NAT2*7B, 9.7%; NAT2*5B, 2.4%). The frequency of NAT2* genotypes consisted of 44%
      of a homozygote of NAT2*4, 49% of a heterozygote of NAT2*4 and mutant genes, and
      7% of a combination of mutant genes. The metabolic activity for procainamide to N
      acetylprocainamide was measured in 11 healthy subjects whose genotype had been
      determined. Although the acetylation activity substantially varied
      interindividually, the variability was considerably reduced after classification
      according to the genotype. The N-acetylprocainamide/procainamide ratio in urinary
      excretion was 0.60 +/- 0.17 (mean +/- SD) for those with NAT2*4/*4, 0.37 +/- 0.06
      for NAT2*4/*6A, 0.40 +/- 0.03 for NAT2*4/*7B, and 0.17 for NAT2*6A/*7B. The
      results indicated that the NAT2* genotype correlates with acetylation of
      procainamide.

PMID- 9164414
TI  - Population pharmacokinetics of atovaquone in patients with acute malaria caused
      by Plasmodium falciparum.
AB  - The population pharmacokinetics of atovaquone were examined in 458 black,
      Oriental, and Malay patients with acute Plasmodium falciparum malaria receiving
      atovaquone alone or concomitantly with other drugs. Oral clearance (CL/F) showed
      a 0.674 power relationship with weight and is similar in Oriental and Malay
      subjects but 58.5% lower in black subjects. On the basis of mean body weight, the
      population estimate of CL/F is 3.28, 8.49, and 9.13 L/hr in black, Oriental, and
      Malay subjects, respectively. The relationship between apparent volume of
      distribution (V area/F) and weight was linear and similar in all three races at
      7.98 L/kg. The population estimate of V area/F is 345, 383, and 428 L in black,
      Oriental, and Malay subjects, respectively. The bioavailability of the high and
      low doses of atovaquone was similar. Neither CL/F nor V area/F were significantly
      affected by age, gender, and the coadministration with chloroguanide (proguanil),
      pyrimethamine, and tetracycline. Half-life (t1/2) showed a 0.326 power
      relationship with weight; thus, the population estimate of t1/2 in black,
      Oriental, and Malay subjects is 72.9, 31.3, and 32.5 hours, respectively. The
      final magnitudes of interpatient variability in CL/F and V area/F were 68% and
      49%, respectively.

PMID- 9164415
TI  - Steady-state pharmacokinetics of delavirdine in HIV-positive patients: effect on
      erythromycin breath test.
AB  - OBJECTIVE: The steady-state kinetics of delavirdine and desisopropyldelavirdine
      were evaluated in human immunodeficiency virus-positive patients after escalating
      oral doses and after repeated oral administrations at the same dose level. STUDY
      DESIGN: Patients (n = 8 males) were given escalating oral doses of delavirdine
      mesylate, in a sequential fashion, over 14 days for phases 1 (200 mg every 8
      hours), 2 (300 mg every 8 hours), and 3 (400 mg every 8 hours). Control patients
      (n = 4 males) were given 300 mg oral doses of drug every 8 hours for all three
      phases. Hepatic CYP3A activity was evaluated with the erythromycin breath test
      (ERMBT). RESULTS: In the escalating-dose group, delavirdine displayed nonlinear
      kinetics as indicated by the decreasing oral clearance, maximum steady-state
      plasma concentration/minimum steady-state plasma concentration ratio, and log
      linear terminal rate constant, as well as by increasing half-life at higher
      doses; the ratio of desisopropyl-delavirdine formation clearance to elimination
      clearance was also reduced. In the control group, the kinetics of delavirdine and
      desisopropyl-delavirdine were unchanged. Plasma protein binding was linear for
      delavirdine in the escalating-dose and control groups; on average, the fraction
      unbound was about 2.3% and 2.0%, respectively. Hepatic CYP3A activity was
      markedly reduced after short- and long-term exposure to all doses of delavirdine
      mesylate. Delavirdine could maximally inhibit 70% to 75% of predose ERMBT values,
      with an IC50 of about 0.9 mumol/L. CONCLUSION: Delavirdine is a potent and
      reversible inhibitor of hepatic CYP3A; it is also a substrate for this CYP450
      isoform. It is likely that delavirdine will exhibit drug-drug interactions when
      coadministered with other CYP3A substrates.

PMID- 9164416
TI  - Pharmacokinetic study of the interaction between rifampin and delavirdine
      mesylate.
AB  - OBJECTIVE: To study the effect of rifampin (INN, rifampicin), a potent inducer of
      cytochrome P450, on the steady-state pharmacokinetics of delavirdine. METHODS:
      Twelve patients who were positive for human immunodeficiency virus, with CD4
      counts ranging from 110 to 483/mm3, were randomized to two groups and studied in
      parallel. Both the control group (n = 5) and the rifampin group (n = 7) received
      400 mg delavirdine mesylate every 8 hours for 30 days; subjects in the rifampin
      group took a 600 mg once-daily dose of rifampin on days 16 through 30. Harvested
      plasma from serial blood samples collected after dosing on days 15, 16, and 30
      was assayed for delavirdine and its N-desalkyl metabolite concentrations with a
      reversed-phase HPLC method. Blood samples obtained on days 16 and 30 were also
      assayed for rifampin by HPLC. RESULTS: Delavirdine mesylate alone and in
      combination with rifampin was well tolerated. On day 30, statistically
      significant differences between groups were observed for all delavirdine
      pharmacokinetic parameters (p < 0.049). In the rifampin group, delavirdine oral
      clearance increased by about 27-fold (p = 0.022), resulting in virtually
      negligible (< 0.09 mumol/L) steady-state through drug concentrations in all
      patients after 2 weeks of concurrent dosing of delavirdine mesylate and rifampin.
      The ratio of metabolite formation to elimination clearance for
      desalkyldelavirdine was significantly higher (3.9 +/- 1.2 versus 0.23 +/- 0.10)
      and delavirdine elimination half-life was significantly shorter (1.7 +/- 1.4
      versus 4.3 +/- 1.3 hours) when delavirdine mesylate was taken with rifampin.
      Rifampin pharmacokinetic parameters on days 16 and 30 were similar to those
      previously reported for normal volunteers. CONCLUSIONS: The findings of this
      study indicate that rifampin induces the metabolism of delavirdine. Therefore
      therapy with rifampin is contraindicated in patients receiving delavirdine
      mesylate.

PMID- 9164417
TI  - Metabolism of rifabutin in human enterocyte and liver microsomes: kinetic
      parameters, identification of enzyme systems, and drug interactions with
      macrolides and antifungal agents.
AB  - Biotransformation of rifabutin, an antibiotic used for treatment of tuberculosis
      in patients infected with the human immunodeficiency virus (HIV), and its
      interactions with some macrolide and antifungal agents were studied in human
      intestinal and liver microsomes. Both liver and enterocyte microsomes metabolized
      rifabutin to 25-O-deacetylrifabutin, 27-O-demethylrifabutin, and 20-, 31-, and 32
      hydroxyrifabutin. The same products (except 25-O-deacetylrifabutin) were formed
      by microsomes from lymphoblastoid cells that contained expressed CYP3A4. The
      apparent Michaelis-Menten constant (Km); approximately 10 to 12 mumol/L) and
      maximal velocity (Vmax; approximately 100 pmol/min/mg of protein) values for CYP
      mediated metabolism were similar in liver and enterocyte microsomes.
      Deacetylation of rifabutin (Km approximately 16 to 20 mumol/L and Vmax
      approximately 50 to 100 pmol/min/mg of protein) was catalyzed by microsomal
      cholinesterase. Clarithromycin, ketoconazole, and fluconazole inhibited CYP
      mediated metabolism of rifabutin in enterocyte microsomes equally or more
      potently than in liver microsomes but had no effect on cholinesterase activity.
      Azithromycin did not inhibit in vitro metabolism of rifabutin. This study
      provides evidence that CYP3A4 and cholinesterase are major enzymes that
      biotransform rifabutin in humans and that intestinal CYP3A4 contributes
      significantly to rifabutin presystemic first-pass metabolism and drug
      interactions with macrolide and antifungal agents.

PMID- 9164418
TI  - The effect of sorivudine on dihydropyrimidine dehydrogenase activity in patients
      with acute herpes zoster.
AB  - OBJECTIVE: Bromovinyl-uracil (BVU) is the principal metabolite of sorivudine, a
      potent anti-zoster nucleoside. BVU binds to, and irreversibly inhibits, the
      enzyme dihydropyrimidine dehydrogenase (DPD). The objective of this study was to
      assess the time course of recovery of DPD activity after oral administration of
      sorivudine in patients with herpes zoster and to correlate restoration of DPD
      activity and levels of uracil with the elimination of sorivudine and its
      metabolite BVU from the circulation. METHODS: Sorivudine was given orally as 40
      mg once-daily doses for 10 consecutive days to a total of 19 patients with herpes
      zoster. Serum sorivudine, BVU, and circulating uracil and DPD activity in
      peripheral blood mononuclear cells (PBMCs) were determined before, during, and
      after administration of sorivudine. RESULTS: BVU was eliminated from the
      circulation within 7 days after the last sorivudine dose. DPD activity in PBMCs,
      which was completely suppressed in 18 of the 19 subjects and markedly suppressed
      in the remaining subject during administration of sorivudine, recovered to
      baseline levels within 19 days after the last dose of sorivudine in all subjects
      and within 14 days in all but one of the subjects. The restoration of DPD
      activity was temporally associated with elimination of BVU from the circulation.
      The elevated uracil concentrations produced by inhibition of DPD activity fell
      rapidly after cessation of sorivudine administration and also were temporally
      associated with elimination of BVU from the circulation. The time course of
      recovery of DPD activity in three patients with renal impairment was similar to
      that of the other subjects. CONCLUSIONS: This study indicates that sorivudine
      therapy is associated with a profound depression of DPD activity. Recovery of DPD
      activity occurred within 4 weeks of the completion of sorivudine therapy, which
      indicates that fluorinated pyrimidines may be safely administered 4 weeks after
      completion of sorivudine therapy.

PMID- 9164419
TI  - Metabolic disposition of lansoprazole in relation to the S-mephenytoin 4'
      hydroxylation phenotype status.
AB  - OBJECTIVE: To assess the possible involvement of CYP2C19 in the metabolism of
      lansoprazole in vivo. METHODS: Sixteen male Korean subjects, who had been
      phenotyped as extensive metabolizers and poor metabolizers of S-mephenytoin 4'
      hydroxylation polymorphism (n = 8 each) with racemic mephenytoin with use of the
      8-hour urine analysis of 4'-hydroxymephenytoin, took an oral dose of 30 mg
      lansoprazole, and blood samples were collected up to 48 hours after dosing.
      Lansoprazole and its metabolites were measured by high-performance liquid
      chromatography with ultraviolet detection. RESULTS: The mean lansoprazole area
      under the concentration-time curve (AUC), elimination half-life (t1/2), and
      apparent oral clearance (CLoral) were significantly (p < 0.001) greater, longer,
      and lower, respectively, in the poor metabolizer than in the extensive
      metabolizer group. The mean values for the AUC of hydroxylansoprazole and AUC
      ratio of hydroxylansoprazole to lansoprazole were significantly (p < 0.01 to p <
      0.001) less in the poor metabolizer than in the extensive metabolizer group,
      whereas those for the AUC of lansoprazole sulfone and ratio of lansoprazole
      sulfone to lansoprazole were greater (p < 0.001) in the former than in the latter
      group. In addition, the log10 4'-hydroxymephenytoin excreted in urine correlated
      significantly (p < 0.01) with the CLoral of lansoprazole. CONCLUSIONS: These
      results suggest that the hydroxylation of lansoprazole cosegregates with the
      genetically determined S-mephenytoin 4'-hydroxylation (CYP2C19) polymorphism in
      the Korean subjects.

PMID- 9164420
TI  - Effects of antiglaucoma drugs on ocular hemodynamics in healthy volunteers.
AB  - BACKGROUND AND PURPOSE: There is evidence that ocular blood flow plays a critical
      role in the clinical course of glaucoma. Hence a reduction in ocular blood flow
      due to topical antiglaucoma treatment should be avoided. The purpose of this
      study was to characterize the effect of antiglaucoma drugs on ocular
      hemodynamics. METHODS: In a double-blind, placebo-controlled, randomized
      crossover study, we investigated the effects of single topical doses of five beta
      blocking agents (befunolol, betaxolol, levobunolol, metipranolol, and timolol),
      two adrenergic agents (clonidine and dipivefrin [INN, dipivefrine]), and a
      parasympathomimetic agent (pilocarpine) on ocular and systemic hemodynamics in
      healthy subjects (n = 10). Fundus pulsation amplitudes in the macula and the
      optic disc were measured to characterize pulsatile choroidal and optic disc blood
      flow, respectively. Moreover, central retinal and ophthalmic artery blood flow
      velocities were measured by Doppler ultrasound. RESULTS: Befunolol, metipranolol,
      timolol, clonidine, and dipivefrin reduced fundus pulsations in the macula and
      the optic disc (-9% to -14% versus baseline). In contrast, betaxolol,
      levobunolol, and pilocarpine had no effect on fundus pulsations. Antiglaucoma
      drugs had no effect on either blood flow velocities in the central retinal or the
      ophthalmic artery or systemic hemodynamics. CONCLUSIONS: Our results indicate
      that befunolol, metipranolol, timolol, clonidine, and dipivefrin reduce choroidal
      and optic disc blood flow. This could be caused by drug diffusion to the choroid,
      which may cause vasoconstriction. Ocular blood flow reduction was not observed
      with betaxolol, levobunolol, or pilocarpine. The lack of effect of all drugs
      under study on central retinal blood flow velocity might partially be the result
      of autoregulative mechanisms. Because optic nerve head blood flow likely plays a
      critical role in the clinical course of glaucoma, the use of antiglaucoma drugs,
      which reduce blood flow, should be reconsidered.

PMID- 9164421
TI  - Myocardial efficiency during calcium sensitization with levosimendan: a
      noninvasive study with positron emission tomography and echocardiography in
      healthy volunteers.
AB  - Dynamic positron emission tomography (PET) with [11C]acetate allows noninvasive
      assessment of myocardial oxygen consumption. In combination with
      echocardiography, PET enables determination of cardiac efficiency (defined as
      useful cardiac work per unit of oxygen consumption). We used this approach to
      compare the effects of levosimendan, a Ca(2+)-dependent calcium sensitizer, with
      dobutamine and sodium nitroprusside in healthy male volunteers. The effects of
      levosimendan on k(mono), an index of oxygen consumption, and cardiac efficiency
      were neutral, whereas the hemodynamic profile was consistent with balanced
      inotropism and vasodilatation. Dobutamine enhanced cardiac efficiency at the
      expense of increased oxygen requirement, but the effects of nitroprusside on
      k(mono) and cardiac efficiency were neutral. This study shows the feasibility of
      PET in phase 1 pharmacodynamic studies and suggests potential energetical
      advantages of calcium sensitization with levosimendan.

PMID- 9164422
TI  - Nitric oxide and shock.
AB  - Shock can be defined as the failure of the circulatory system to provide
      necessary cellular nutrients, including oxygen, and to remove metabolic wastes.
      Although it is now recognized that more than 100 different forms of shock exist,
      this recognition is more a reflection of the widespread use of the term to
      describe a variety of disease states. For the purpose of this monograph, we
      concentrate on various forms of cardiovascular shock, in particular, shock that
      may be linked to inappropriate vasodilation from overproduction of the endogenous
      vasodilator, nitric oxide. Some forms of shock have been extensively studied, and
      convincing evidence exists for the role of nitric oxide. Other disease states
      have been less well characterized in terms of their association with excess
      nitric oxide production. Available evidence of a role for nitric oxide is
      discussed in the hope of stimulating the interest of investigators to explore
      these areas more thoroughly.

PMID- 9164423
TI  - Combining serotonin reuptake inhibitors and bupropion in partial responders to
      antidepressant monotherapy.
AB  - BACKGROUND: Many patients with affective illness show partial or otherwise
      unsatisfactory responses to standard treatments, encouraging trials of
      combinations of pharmacologically dissimilar antidepressants. METHOD: Records of
      consecutive outpatients with affective disorders only partially responsive to
      treatment with a serotonin reuptake inhibitor (SRI) or bupropion, alone, were
      reviewed for changes in specific symptoms and risks of adverse events when an SRI
      and bupropion were combined. RESULTS: Greater symptomatic improvement was found
      in 19 (70%) of 27 subjects during a mean +/- SD of 11 +/- 14 months of combined
      daily use of bupropion (243 +/- 99 mg) with an SRI (31 +/- 16 mg fluoxetine
      equivalents) than with either agent alone. Adverse effect risks were similar to
      those associated with each monotherapy, with a > 10% incidence of sexual
      dysfunction (N = 11, 41%), insomnia (N = 6, 22%), anergy (N = 4, 15%), and tremor
      (N = 3, 11%) during combined therapy; there were no seizures. CONCLUSION: With
      conservative dosing and close monitoring, combinations of SRIs with bupropion in
      this uncontrolled clinical series appeared to be safe and often more effective
      than monotherapy.

PMID- 9164424
TI  - A double-blind comparison of fluvoxamine and paroxetine in the treatment of
      depressed outpatients.
AB  - BACKGROUND: Fluvoxamine and paroxetine, both serotonin selective reuptake
      inhibitors (SSRIs), were compared at two centers in a 7-week double-blind study
      in outpatients with major depression, diagnosed by DSM-III-R criteria. METHOD:
      Sixty patients were randomly assigned to receive dosage titrated upward to
      between 50-150 mg/day of fluvoxamine (N = 30) or 20-50 mg/day of paroxetine (N =
      30). The mean +/- SD daily dose administered at the last assessment was 102 +/-
      44 mg/day for fluvoxamine and 36 +/- 13 mg/day for paroxetine. Sixteen (53%)
      fluvoxamine-treated patients and 10 (33%) paroxetine-treated patients were
      titrated to the maximum permissible dosage of either drug. Sample size was
      calculated to provide at least 85% power at 5% level of significance to detect at
      least a 1.00-point difference in mean severity of adverse events, assuming a
      standard deviation of 1.0. RESULTS: Fluvoxamine and paroxetine were similarly
      effective in ameliorating depression as demonstrated by mean total scores of 10.9
      +/- 7.3 (p < .00) and 11.5 +/- 7.4 (p < .00), respectively, in the Hamilton
      Rating Scale for Depression (HAM-D). Adverse events were mostly mild to moderate
      in severity. The most common events were headache (N = 17, 57%), nausea (N = 14,
      47%), sweating (N = 10, 33%), somnolence (N = 9, 30%), diarrhea (N = 9, 30%), dry
      mouth (N = 8, 27%), dizziness (N = 8, 27%), and, among males, impotence (N = 3,
      21%) and ejaculatory abnormality (N = 3, 21%) in the paroxetine group, and
      headache (N = 12, 40%), somnolence (N = 12, 40%), nausea (N = 11, 37%), dry mouth
      (N = 11, 37%), insomnia (N = 9, 30%), asthenia (N = 7, 23%), and dyspepsia (N =
      7, 23%) in the fluvoxamine group. The only statistically significant difference
      between treatment groups was for sweating (33% paroxetine vs. 10% fluvoxamine, p
      = .028). CONCLUSION: Observed differences in some side effects, although not
      statistically significant, indicate that when a patient has difficulty tolerating
      one SSRI, the clinician may choose to change to a different agent within the same
      class.

PMID- 9164425
TI  - Quality of life and panic-related work disability in subjects with infrequent
      panic and panic disorder.
AB  - BACKGROUND: Panic disorder is associated with poor quality-of-life (QOL).
      However, little is known regarding the impact of panic disorder or infrequent
      panic on work-related disability. The purpose of this study was (1) to document
      QOL and panic-related work disability in subjects with panic disorder or
      infrequent panic, (2) to identify independent predictors of QOL and disability,
      and (3) to compare outcomes in subjects with panic disorder versus infrequent
      panic. METHOD: This cross-sectional community survey included 97 subjects with
      panic and matched controls. Subjects were screened for panic disorder or
      infrequent panic using the Structured Clinical Interview for DSM-III-R. The QOL
      questionnaire addressed life satisfaction as well as panic-related work
      disability. A structured interview assessed possible predictors of impaired QOL
      including comorbidity, illness attitudes and behaviors, coping style, family
      measures, and symptom perceptions. RESULTS: QOL was significantly (p < or = .001)
      poorer in subjects with panic than in controls. Comorbid depression, social
      support, worry, and severity of chest pain predicted QOL. Although subjects with
      infrequent panic reported a lower QOL than controls, subjects with panic disorder
      had more panic-related disability and poorer QOL than those with infrequent
      panic. Predictors of work disability included panic frequency, illness attitudes,
      family dissatisfaction, and gender. CONCLUSION: Although both infrequent panic
      and panic disorder impact QOL and disability, panic disorder has a greater
      effect. Using predictors, patient education, provision of support, and focused
      therapy could potentially improve QOL and disability.

PMID- 9164426
TI  - Fluvoxamine in the treatment of compulsive buying.
AB  - BACKGROUND: The authors report the results of an open trial of fluvoxamine in the
      treatment of compulsive buying. METHOD: Ten nondepressed subjects were recruited
      through word-of-mouth and rnet restrictive inclusion/exclusion criteria. Subjects
      were assessed with the Yale-Brown Obsessive-Compulsive Scale modified for
      compulsive buying, the Clinical Global Impression scale, and other measures.
      After a single-blind 1-week placebo run-in, subjects received fluvoxamine up to
      300 mg daily for 9 weeks. RESULTS: Nine of 10 subjects improved and were less
      preoccupied with shopping, spent less time shopping, and reported spending less
      money. CONCLUSION: We conclude that compulsive buyers can be recruited for
      research and their symptoms measured and monitored and, finally, that fluvoxamine
      may be effective in its treatment.

PMID- 9164427
TI  - Clinical effects of buspirone in social phobia: a double-blind placebo-controlled
      study.
AB  - BACKGROUND: The results of open pilot studies suggest that the serotonin-1A (5
      HT1A) receptor agonist buspirone might be effective in social phobia. METHOD: In
      the present study, the efficacy of buspirone was investigated in patients with
      social phobia using a 12-week double-blind placebo-controlled design. Thirty
      social phobic patients (DSM-IV) were treated with either buspirone 30 mg daily or
      placebo. Efficacy of treatment was measured using the Social Phobia Scale
      (subscores anxiety and avoidance) and the Hamilton Rating Scale for Anxiety.
      RESULTS: Taking a reduction of 50% or more on the Social Phobia Scale as a
      criterion for clinically relevant improvement, only 1 patient on buspirone and 1
      on placebo were classified as responder to treatment. A subjective and clinically
      relevant improvement was reported by 4 patients (27%) on buspirone and 2 patients
      (13%) on placebo. There were no statistically significant differences between
      buspirone and placebo on any of the outcome measures. Generally speaking,
      buspirone was well tolerated. CONCLUSION: The results of the study do not support
      the results of open studies, in which a reduction of social anxiety and social
      avoidance was reported in patients with social phobia treated with buspirone.

PMID- 9164428
TI  - Study of compulsive buying in depressed patients.
AB  - BACKGROUND: Compulsive buying is defined by the presence of repetitive impulsive
      and excessive buying leading to personal and familial distress. Patients with
      this disorder also suffer from mood disorder in 50% to 100% of the cases studied,
      and antidepressants help to decrease the frequency and the severity of
      uncontrolled buying. To define the correlation between compulsive buying and
      depression, we assessed this behavior among 119 inpatients answering to DSM-III-R
      criteria for major depressive episode. Additionally, we evaluated for comorbidity
      in the patients suffering from compulsive buying and in those free from this
      disorder. Impulsivity and sensation seeking were also compared in the two groups.
      METHOD: Diagnosis of compulsive buying was made using standardized criteria and a
      specific rating scale. Diagnosis of depression and assessment of comorbidity were
      investigated using the Mini International Neuropsychiatric Interview and a
      modified version of the Minnesota Impulsive Disorders Interview. All patients
      answered the Zuckerman Sensation-Seeking Scale and the Barrat Impulsivity Rating
      Scale. RESULTS: The prevalence of the disorder was 31.9%; 38 of the 119 depressed
      patients were diagnosed as compulsive buyers. Patients from the compulsive buying
      group were younger in age, more often women than men, and more frequently
      unmarried. They presented more often than others with recurrent depression
      (relative risk = 1.4), disorders associated with deficits in impulse control such
      as kleptomania (relative risk = 8.5) or bulimia (relative risk = 2.8),
      benzodiazepine abuse or dependence disorder (relative risk = 4.7), and two or
      more dependence disorders (relative risk = 1.99). Subscores for experience
      seeking using the Zuckerman Sensation-Seeking Scale were significantly higher (p
      = .04) and scores of impulsivity were much higher (p < .0001) than corresponding
      scores in the group without compulsive buying behavior. CONCLUSION: Compulsive
      buying is frequent among depressed patients. In most cases, the behavior is
      associated with other impulse control disorders or dependence disorders and a
      high level of impulsivity.

PMID- 9164429
TI  - Bupropion for SSRI-induced fatigue.

PMID- 9164430
TI  - Novel use of tramadol hydrochloride in the treatment of Tourette's syndrome.

PMID- 9164431
TI  - Safety of amobarbital.

PMID- 9164432
TI  - Transient, paroxysmal, shock-like paresthesias associated with paroxetine
      initiation.

PMID- 9164433
TI  - Benztropine in the treatment of venlafaxine-induced sweating.

PMID- 9164435
TI  - Pharmacologic properties of venlafaxine.

PMID- 9164434
TI  - Stereotypic movement disorder.

PMID- 9164436
TI  - Impact of a smoking ban on a locked psychiatric unit.

PMID- 9164437
TI  - Advances in radiation oncology.

PMID- 9164438
TI  - Combined modality therapy of solid tumours.

PMID- 9164439
TI  - Chemotherapy.

PMID- 9164440
TI  - Gene therapy of cancer.

PMID- 9164441
TI  - Antiangiogenesis for cancer therapy.

PMID- 9164442
TI  - Cancer genes and molecular oncology in the clinic.

PMID- 9164443
TI  - Clinical promise of tumour immunology.

PMID- 9164444
TI  - Global burden of cancer.

PMID- 9164445
TI  - Cancer prevention.

PMID- 9164446
TI  - Troglitazone for non-insulin-dependent diabetes mellitus.

PMID- 9164447
TI  - Topiramate for epilepsy.

PMID- 9164448
TI  - Through a magnet, clearly.

PMID- 9164450
TI  - Fit to be tied.

PMID- 9164449
TI  - Common fold, common function, common origin?

PMID- 9164451
TI  - Peptide nucleic acids and prebiotic chemistry.

PMID- 9164452
TI  - Plugging into actin's architectonic socket.

PMID- 9164453
TI  - Deposition of macromolecular coordinates resulting from crystallographic and NMR
      studies.

PMID- 9164455
TI  - NMR structure of the 35-residue villin headpiece subdomain.
AB  - The NMR structure of an autonomously folding subdomain from villin headpiece is
      reported. It forms a novel three helix structure with the actin-binding residues
      arrayed on the C-terminal helix.

PMID- 9164454
TI  - Crystal structure of a calponin homology domain.
AB  - The three-dimensional structure of the calponin homology domain present in many
      actin binding cytoskeletal and signal-transducing proteins has been determined at
      2.0 A resolution.

PMID- 9164456
TI  - Picture story. Death grip.

PMID- 9164457
TI  - Crystal structure of phytase from Aspergillus ficuum at 2.5 A resolution.
AB  - Phytase is a high molecular weight acid phosphatase. The structure has an
      alpha/beta-domain similar to that of rat acid phosphatase and an alpha-domain
      with a new fold.

PMID- 9164458
TI  - Solution structure of the carbohydrate-binding B-subunit homopentamer of
      verotoxin VT-1 from E. coli.

PMID- 9164459
TI  - A minor groove binding track in reverse transcriptase.

PMID- 9164460
TI  - Solution structure of the N-terminal domain of the delta subunit of the E. coli
      ATPsynthase.
AB  - NMR studies of the delta subunit of the Escherichia coli F1F0-ATPsynthase reveal
      that it consists of an N-terminal six alpha-helix bundle and a less well ordered
      C terminus. Both domains are part of one of two separate connections between F1
      and F0.

PMID- 9164461
TI  - A comparison between molecular dynamics and X-ray results for dissociated CO in
      myoglobin.
AB  - The distribution of carbon monoxide after photodissociation in the myoglobin haem
      pocket has been investigated using molecular dynamics simulations at 300 K. The
      results show that both intermediates (one close to the haem iron and one further
      away) observed in recent low temperature X-ray studies of photodissociated CO
      have a high probability of occurrence, even at ambient temperatures. The fact
      that the O of CO is oriented toward the haem iron in the closer intermediate
      provides an explanation for the slow rate of CO geminate rebinding. A refinement
      against X-ray data generated from the molecular dynamics simulations indicates
      that the CO has a broader distribution in the haem pocket than is apparent from
      the experimental electron density. This effect is likely to be general for
      systems containing highly mobile groups.

PMID- 9164462
TI  - Ultrafast rotation and trapping of carbon monoxide dissociated from myoglobin.
AB  - The nature of ligand motion within proteins has been investigated by measuring
      femtosecond time-resolved infrared (IR) spectra of CO photodissociated from the
      haem of myoglobin. Upon dissociation, the CO rotates approximately 90 degrees and
      becomes trapped within a ligand docking site located near the binding site. Two
      trajectories, distinguished spectroscopically and kinetically with time constants
      of 0.20 +/- 0.05 ps and 0.52 +/- 0.10 ps, lead to CO located within the docking
      site with opposite orientations. The protein reorganizes about the "docked' CO
      with a time constant of 1.6 +/- 0.3 ps and quickly establishes an energetic
      barrier that inhibits the reverse rebinding process.

PMID- 9164463
TI  - Crystal structure of the two RNA binding domains of human hnRNP A1 at 1.75 A
      resolution.
AB  - Heterogeneous ribonucleoprotein A1 (hnRNP A1) is an abundant eukaryotic nuclear
      RNA binding protein. A1 is involved in the packaging of pre-mRNA into hnRNP
      particles, transport of poly A+ mRNA from the nucleus to the cytoplasm and may
      modulate splice site selection. The crystal structure of A1(RBD1,2) reveals two
      independently-folded RNA binding domains (RBDs) connected by a flexible linker.
      Both RBDs are structurally homologous to the U1A(RBD1), and have their RNA
      binding platforms oriented in an anti-parallel fashion. The anti-parallel
      arrangement of the A1 RNA binding platforms suggests mechanisms for RNA
      condensation and ways of bringing together distant RNA sequences for RNA
      metabolism such as splicing or transport.

PMID- 9164464
TI  - The repeating segments of the F-actin cross-linking gelation factor (ABP-120)
      have an immunoglobulin-like fold.
AB  - The 120,000 M(r) gelation factor and alpha-actinin are among the most abundant F
      actin cross-linking proteins in Dictyostelium discoideum. Both molecules are rod
      shaped homodimers. Each monomer chain is comprised of an actin-binding domain and
      a rod domain. The rod domain of the gelation factor consists of six 100-residue
      repetitive segments with high internal homology. We have now determined the three
      dimensional structure of segment 4 of the rod domain of the gelation factor from
      D. discoideum using NMR spectroscopy. The segment consists of seven beta-sheets
      arranged in an immunoglobulin-like (Ig) fold. This is completely different from
      the alpha-actinin rod domain which consists of four spectrin-like alpha-helical
      segments. The gelation factor is the first example of an Ig-fold found in an
      actin-binding protein. Two highly homologous actin-binding proteins from human
      with similar sequences to the gelation factor, filamin and a 280,000 M(r) actin
      binding protein (ABP-280), share conserved residues that form the core of the
      gelation factor repetitive segment structure. Thus, the segment 4 structure
      should be common to this subfamily of the spectrin superfamily. The structure of
      segment 4 together with previously published electron microscopy data, provide an
      explanation for the dimerization of the whole gelation factor molecule.

PMID- 9164466
TI  - Structure of a bifunctional membrane-RNA binding protein, influenza virus matrix
      protein M1.
AB  - Matrix protein (M1) of influenza virus is a bifunctional protein that mediates
      the encapsidation of RNA-nucleoprotein cores into the membrane envelope. It is
      therefore required that M1 binds both membrane and RNA simultaneously. The X-ray
      crystal structure of the N-terminal portion of type A influenza virus M1-amino
      acid residues 2-158-has been determined at 2.08 A resolution at pH 4.0. The
      protein forms a dimer. A highly positively charged region on the dimer surface is
      suitably positioned to bind RNA while the hydrophobic surface opposite the RNA
      binding region may be involved in interactions with the membrane. The membrane
      binding hydrophobic surface could be buried or exposed after a conformational
      change.

PMID- 9164465
TI  - Crystal structures of HINT demonstrate that histidine triad proteins are GalT
      related nucleotide-binding proteins.
AB  - Histidine triad nucleotide-binding protein (HINT), a dimeric purine nucleotide
      binding protein from rabbit heart, is a member of the HIT (histidine triad)
      superfamily which includes HINT homologues and FHIT (HIT protein encoded at the
      chromosome 3 fragile site) homologues. Crystal structures of HINT-nucleotide
      complexes demonstrate that the most conserved residues in the superfamily mediate
      nucleotide binding and that the HIT motif forms part of the phosphate binding
      loop. Galactose-1-phosphate uridylyltransferase, whose deficiency causes
      galactosemia, contains tandem HINT domains with the same fold and mode of
      nucleotide binding as HINT despite having no overall sequence similarity.
      Features of FHIT, a diadenosine polyphosphate hydrolase and candidate tumour
      suppressor, are predicted from HINT-nucleotide structures.

PMID- 9164468
TI  - Mechanisms of methicillin resistance in staphylococci.
AB  - The continuously high prevalence of methicillin-resistant staphylococci (MRS)
      throughout the world is a constant threat to public health, owing to the
      multiresistant characteristics of these bacteria. Methicillin resistance is
      phenotypically associated with the presence of the penicillin-binding protein 2a
      (PBP2a) not present in susceptible staphylococci. This protein has a low binding
      affinity for beta-lactam antibiotics. It is a transpeptidase which may take over
      cell wall synthesis during antibiotic treatment when normally occurring PBPs are
      inactivated by ligating beta-lactams. PBP2a is encoded by the mecA gene, which is
      located in mec, a foreign DNA region. Expression of PBP2a is regulated by
      proteins encoded by the plasmid-borne blaR1-bla1 inducer-repressor system and the
      corresponding genomic mecRl-mecl system. The blaRl-blal products are important
      both for the regulation of beta-lactamase and for mecA expression. Methicillin
      resistance is influenced by a number of additional factors, e.g. the products of
      the chromosomal fem genes which are important in the synthesis of normal
      peptidoglycan precursor molecules. Inactivation of fem-genes results in
      structurally deficient precursors which are not accepted as cell wall building
      blocks by the ligating PBP2a transpeptidase during antibiotic treatment. This may
      result in reduced resistance to beta-lactam antibiotics. Inactivation of genes
      affecting autolysis has shown that autolytic enzymes are also of importance in
      the expression of methicillin resistance. Methicillin resistance has evolved
      among earth microorganisms for protection against exogenous or endogenous
      antibiotics. Presumably the mec region was originally transferred from coagulase
      negative staphylococci (CNS) to Staphylococcus aureus (SA). A single or a few
      events of this kind with little subsequent interspecies transfer had been
      anticipated. However, recent data suggest a continuous horizontal acquisition by
      S. aureus of mec, being unidirectional from CNS to SA. Methicillin resistance may
      also be associated with mechanisms independent of mecA, resulting in borderline
      methicillin resistance. These mechanisms include beta-lactamase hyperproduction,
      production of methicillinases, acquisition of structurally modified normal PBPs,
      or the appearance of small colony variants of SA. Most MRS are multiresistant,
      and the mec region may harbour several resistance determinants, resulting in a
      clustering of resistance genes within this region.

PMID- 9164467
TI  - TNF blockade in rheumatoid arthritis: implications for therapy and pathogenesis.
AB  - The role of the immune response in rheumatoid arthritis (RA) is a subject of
      debate, although it is widely believed to be a T-cell-driven disease. Progress is
      being hindered by lack of convincing evidence of a defined specific antigen
      initiating or perpetuating the response. Clinical trials using monoclonal
      antibodies directed against T-cell surface molecules such as CD4. CD5, and CD7
      have thus far not provided evidence of efficacy. The negative data may reflect
      inadequate dosing or could suggest that indiscriminate depletion of T cells is
      insufficient by itself as a therapeutic strategy. Blocking proinflammatory
      cytokines (e.g. TNF alpha, IL-1) or augmenting anti-inflammatory cytokines (e.g.
      IL-10) offers an alternative approach to therapy. Clinical trials using
      monoclonal anti-TNF alpha have been particularly successful in controlling
      inflammation and markedly reducing acute phase proteins and cellular ingress.
      However, because disease invariably relapses, repeated therapy is necessary.
      Preliminary experience suggests that this is possible. Anti-TNF therapy for RA
      has defined a molecular target and new approach for treating immuno-inflammatory
      disorders.

PMID- 9164469
TI  - Distribution of serotypes, IS901 and a 40 kDa protein in Mycobacterium avium
      complex strains isolated from man and animals in Denmark.
AB  - The aim of the present study was to characterize all strains of the Mycobacterium
      avium complex isolated in Denmark in 1993. A total of 141 M. avium complex
      strains (86 from man, 38 from animals, and 17 from peat) were analysed by
      serotyping, ELISA specific for a 40 kDa protein, and IS901-specific PCR. Serotype
      analysis showed that the most frequent serotypes among human strains were
      serotype 4 (27%) and serotype 6 (19%), which differs from an earlier survey where
      serotype 1 was most prevalent. The most frequent serotypes in animals were
      serotype 2 (53%) and serotype 6 (13%), whereas the most prevalent serotypes among
      strains isolated from peat were serotype 4 (29%) and serotype 9 (18%). There was
      a concurrent appearance of IS901 and p40 in all strains. Only M. avium complex
      strains isolated from animals, and belonging to serotype 1 or serotype 2,
      contained the IS901/p40 markers. The different distribution of serotypes of M.
      avium complex strains in animals and man, and the presence of IS901/p40
      exclusively in animal strains, suggests that transmission of M. avium from
      animals to man is not of significance in Denmark.

PMID- 9164470
TI  - A xenograft line of human teratocarcinoma established by serial transplantation
      in severe combined immunodeficient (SCID) mice.
AB  - We established a xenograft line of human teratocarcinoma (TC-1) and characterized
      the pluripotency of differentiation of the neoplastic cells. A teratocarcinoma
      specimen obtained from a primary mediastinal lesion (22-year-old male patient)
      was inoculated subcutaneously into severe combined immunodeficient (SCID) mice.
      The carcinoma formed tumors in the mice. We established a xenograft line by
      serial passage of the tumor in vivo. The primary tumor was composed of papillary
      and pseudoglandular nests of highly atypical epithelial cells with foci of
      glomeruloid structures. The metastatic cells showed apparent production of mucin
      and differentiation to striated muscle. The xenograft line TC-1 retained the
      basic histopathological features seen in the primary and metastatic cells. The
      xenograft line showed focal differentiation to cartilage through serial passages.
      Immunohistochemical studies with anti-alpha-fetoprotein (AFP) demonstrated
      positive immunoreactivity on the TC-1 cells. Serum AFP levels were also elevated
      in the TC-1-bearing SCID mice. The human teratocarcinoma xenograft line TC-1 will
      be useful for studying the differentiation mechanism in human totipotent stem
      cells.

PMID- 9164471
TI  - Direct cytotoxic response of human lymphocytes to porcine PHA-lymphoblasts and
      lymphocytes.
AB  - Transplantation of cells and organs from pigs to human beings offers potential
      treatment for medical conditions such as diabetes, kidney and heart failure, and
      Parkinson's disease. When the antibody-mediated hyperacute rejection barrier is
      overcome, a xenograft may not be treated as an allograft by the human immune
      system. Without prior culture with porcine cells, human lymphocytes are cytotoxic
      to some porcine cells. Our aim was to functionally characterize this direct
      cytotoxic response to porcine PHA-lymphoblasts and lymphocytes. Peripheral blood
      mononuclear cells from seven of eight human beings were cytotoxic to porcine PHA
      lymphoblasts in bulk chromium-release assays, but not to the porcine lymphocytes
      from which the PHA-lymphoblasts were derived. The NK cell-sensitive cell line
      K562 only partly blocked the response to the PHA-lymphoblasts. IL-2-expanded
      clones of human lymphocytes were able to discriminate between PHA-lymphoblasts
      from two pigs and unable to lyse K562. When using IL-2 to make the anti-porcine
      cells proliferate under limiting dilution conditions, the proliferation and/or
      function of these cells did not conform to single-hit kinetics. All the
      observations from experiments with cells in bulk cultures and as short-term
      clones suggest that the direct cytotoxic response of human lymphocytes to porcine
      cells is heterogeneous and composed of a small population of in vivo-activated T
      cells as well as NK cells.

PMID- 9164472
TI  - Aedes albopictus (Diptera:Culicidae) is incompetent as a vector of hepatitis C
      virus.
AB  - In laboratory experiments, Aedes albopictus females were fed hepatitis C virus
      (HCV)-infected human blood with a unit-feeding apparatus. Pools of engorged
      females were tested at various time intervals after their blood meal for the
      presence of HCV RNA using two methods in parallel: reverse transcription-nested
      polymerase chain reaction (PCR) and PCR with the Amplicor HCV system. Comparable
      results were obtained with both methods. Mosquitoes were found to be positive
      only immediately and 24 h after feeding. Moreover, female progeny produced
      negative results. Our results indicate that the Ae.albopictus strain used is
      incompetent as a vector of HCV.

PMID- 9164473
TI  - Restriction pattern variability of respiratory syncytial virus during three
      consecutive epidemics in Denmark.
AB  - A PCR-based assay was used to distinguish between respiratory syncytial virus
      (RSV) group A and B in order to analyze their prevalence in Denmark in three
      consecutive epidemics during the winters of 1992/93, 1993/94 and 1994/95. A total
      of 96 RSV strains isolated from hospitalized children were examined, showing
      alternation of group prevalence. Furthermore, the genetic variability of the RSV
      isolates was illustrated by restriction enzyme analysis of PCR products
      originating from a part of the F and G proteins that has been reported to be
      highly variable. We found that, in general, different genome types predominated
      each year, some types being present in consecutive epidemics, indicating a
      contribution of strains circulating unattended between outbreak seasons, while
      others seemed to disappear or became undetectable, being replaced by emerging
      types. Some of the genome types found seemed related to strains isolated up to
      more than two decades ago in other parts of the world. This indicates that the
      temporal fluctuation in predominance of genome types presumably caused by
      selective pressure exerted by host immunity is due to the favoring of strains
      from a pool of globally circulating, genetically relatively stable genome types,
      rather than a molecular evolution in strains induced or directed by
      immunoselective pressure.

PMID- 9164474
TI  - The determination of neutrophil membrane fluidity in patients with hepatitis B: a
      fluorescence polarization study.
AB  - Although numerous studies on abnormality of neutrophil function in patients with
      viral hepatitis have previously been reported, little is known about mechanisms
      of neutrophil dysfunction. To investigate mechanisms of neutrophil dysfunction in
      these patients, neutrophil membrane fluidity was measured by fluorescence
      polarization technique in 76 hepatitis patients. The results showed that membrane
      fluidity of neutrophils from patients with chronic active hepatitis (CAH) or
      subfulminant hepatic failure (SFHF) was much lower than that in normal controls
      (p < 0.01), but such a difference could not be found in patients with acute
      hepatitis (p > 0.05). Furthermore, recombinant interleukin-2 could significantly
      increase membrane fluidity, while lipopolysaccharide decreased membrane fluidity
      of neutrophils (p < 0.01, p < 0.001). The present study indicates that there is
      abnormal membrane fluidity of neutrophils in patients with CAH and SFHF.
      Neutrophil dysfunction in hepatitis patients may be partly due to altered
      membrane fluidity.

PMID- 9164475
TI  - Adenocarcinoma of the cervix and adenocarcinoma of the endometrium: distinction
      with PCR-mediated detection of HPV DNA.
AB  - The differential diagnosis between primary endocervical adenocarcinoma and
      adenocarcinoma originating in the endometrium may in some cases be difficult. The
      two cancer types have a different genesis, with human papillomavirus (HPV) as an
      important causal factor in the development of primary cervical carcinoma. In this
      study, the paraffin-embedded cervical tissues from 23 patients with stage II
      endometrial carcinoma and from 50 patients with primary cervical adenocarcinoma
      were examined for HPV DNA of types 16, 18, and 33. HPV DNA was demonstrated in
      70% of the primary endocervical adenocarcinomas and in none of the endometrial
      carcinomas. It is concluded that HPV detection may be useful in the differential
      diagnosis of some cases of cervical and endometrial adenocarcinoma.

PMID- 9164476
TI  - Identification of porcine Pneumocystis carinii as a genetically distinct organism
      by DNA amplification.
AB  - DNA was amplified from lung samples from three piglets infected with Pneumocystis
      carinii, using oligonucleotide primers designed to the P. carinii mitochondrial
      large subunit ribosomal RNA gene. The nucleotide sequence of the amplification
      product was determined and indicated lack of sequence variation among these pig
      derived P. carinii samples at this locus. The data showed that porcine P. carinii
      was genetically distinct from P. carinii isolated from other mammalian host
      species.

PMID- 9164477
TI  - Intratumoral heterogeneity in prostate cancer demonstrated by volume-weighted
      mean nuclear volume.
AB  - This study was conducted to investigate the degree of heterogeneity of the volume
      weighted mean nuclear volume (MNV) calculated from radical prostatectomy
      specimens, and to evaluate how closely the MNV calculated from transrectal biopsy
      specimens reflected the overall malignancy. MNV was evaluated using 77 sections
      of histological specimens from 9 patients who underwent radical prostatectomy at
      Shizuoka City Hospital between January 1990 and December 1995. The MNV values
      calculated from radical prostatectomy specimens were compared with those
      calculated from preoperative transrectal biopsy specimens. MNV was judged to be
      homogeneous in six cases and heterogeneous in three cases. Of the heterogeneous
      cases, MNV calculated from the transrectal biopsy specimens was judged to be
      underestimated in 2 of 3 cases. This study shows that intratumoral heterogeneity
      of prostate cancer may affect clinical estimates of the grade of malignancy based
      on the MNV, and indicates the need for a sufficient number of specimens in order
      to evaluate the MNV by transrectal biopsy.

PMID- 9164478
TI  - A case control study of chorioamniotic infection and histological
      chorioamnionitis in stillbirth.
AB  - In order to elucidate the role and aetiology of chorioamnionitis in stillbirth a
      case referent study was carried out in 58 pregnant women with late foetal death
      (cases) and in 58 pregnant women at term with live foetus (referents) matched for
      age and parity in Maputo Mozambique. Samples from women, stillborns and
      liveborns, were collected for microbiological and histological assessment.
      Histological chorioamnionitis was diagnosed in 96% of the cases and in 67% of the
      referents (OR = 13.5; 95% CI: 2.9-123.9). Escherichia coli was the species most
      frequently isolated in stillborns; in 14/16 (88%) cases it was isolated from
      intracardiac fluid. E. coli was associated with chorioamnionitis in 28% of the
      stillborns as compared to 5% of the referents (OR = 6.9; 95% CI: 1.4-65.4). No
      group B streptococci were recovered from any placenta or newborn. Vasculitis was
      present in 12 (21%) cases and in 3 (5%) referents (OR = 4.8; 95%, CI: 1.2-27.7).
      Histological chorioamnionitis was thus associated with stillbirth. E. coli was
      common in stillborns. The presence of vasculitis in one fifth of the stillborns
      indicated that the foetus was alive at the onset of infection.

PMID- 9164479
TI  - DNA glycosylases.

PMID- 9164480
TI  - XPC interacts with both HHR23B and HHR23A in vivo.
AB  - XP group C protein (XPC) and a human homologue of RAD23, HHR23B, have previously
      been shown to copurify in a tightly associated complex. Here, we show that XPC
      interacts in vivo, by means of the yeast two-hybrid system, with both HHR23B and
      a second homologue of RAD23, HHR23A. Domain mapping studies have revealed that
      both RAD23 homologues interact with XPC at the same highly conserved region in
      the C-terminal half of the protein. XPC mutants deleted within this domain and
      that are highly deficient in binding both RAD23 homologues are also highly
      defective in complementing XPC cells in vivo. Domain mapping studies have also
      identified a region in the N-terminal half of HHR23B that contains the XPC
      interactive site. This domain is highly conserved among HHR23B, HHR23A, and
      RAD23.

PMID- 9164481
TI  - The identification and purification of a novel mammalian DNA ligase.
AB  - Using a combination of biochemical fractionation and adenylation assays, we have
      purified a novel 44 kDa protein from human cells which rejoins DNA double-strand
      breaks. Its rejoining properties and its ability to form an adenylation product
      with ATP, which can be rapidly dissociated by the presence of DNA breaks, show
      that this protein is a DNA ligase. As four mammalian DNA ligases have been
      previously identified we have named this DNA ligase V. Silver staining of the
      most purified fraction on denaturing polyacrylamide gels reveals a protein
      doublet of 46/44 kDa of which only the lower band becomes adenylated. Assay of
      this protein, along with two defined DNA ligases, against DNA templates
      containing either double and single-strand breaks shows that unlike other DNA
      ligases, DNA ligase V does not join nicked templates with high efficiency.
      However, this DNA ligase can join double-strand breaks with a similar efficiency
      to DNA ligase 1. This result indicates that there may be different types of DNA
      ligases in mammalian cells which may have specific cellular functions.

PMID- 9164482
TI  - Abnormal DNA repair activities in lymphocytes of workers exposed to 1,3
      butadiene.
AB  - Exposure to high concentrations of butadiene has been shown to cause cancer among
      exposed workers. We have conducted a biomarker study to elucidate whether current
      butadiene exposure conditions are hazardous to workers. Twenty-four workers
      exposed consistently to butadiene were matched with 19 co-workers who had much
      less contact with butadiene and who served as our controls. In the standard
      cytogenetic assay, there was no difference in chromosome aberration frequencies
      between the exposed and control groups. In the challenge assay, the exposed group
      shows a consistent, but non-significant, increase in chromosome aberrations
      indicating some abnormality in DNA repair response. The observed dicentric
      frequency in the challenge assay (indicative of abnormal repair of damaged
      chromosomes) is significantly correlated with a butadiene metabolite, 1,2
      dihydroxy-4-(N-acetylcysteinyl)butane, in urine (r = 0.52; p = 0.04).
      Furthermore, cigarette smokers had consistently abnormal repair response compared
      with non-smokers for both the control and exposed groups. A small subset of the
      studied workers were evaluated for toxicant-induced DNA repair deficiency using
      an independent cat-host cell reactivation (CAT-HCR) assay. When cigarette smokers
      and non-smokers were combined in our analysis, we observed that the exposed group
      (n = 9) had a significant reduction of DNA repair activities (p = 0.009) compared
      with the control group (n = 6). Cigarette smoking contributed significantly to
      the effect as exposed smokers (n = 4) had a significant reduction in DNA repair
      activities (p = 0.04) compared with exposed non-smokers. The results from the two
      independently conducted assays support each other and confirm the previously
      reported abnormal DNA repair response in another group of butadiene workers. In
      conclusion, our data indicates that exposure to environmental toxicants, such as
      butadiene, can cause DNA repair defects. Therefore, the current butadiene
      exposure conditions are still hazardous to workers. However, our data indicates
      that butadiene is not a potent genotoxic agent. Furthermore, the butadiene
      induced effect is significantly enhanced by the cigarette smoking habit.

PMID- 9164483
TI  - An Escherichia coli topB mutant increases deletion and frameshift mutations in
      the supF target gene.
AB  - We have improved a system to examine forward mutations that occurred in the supF
      gene of Escherichia coli placed on a multicopy plasmid. Using this system, we
      determined the mutational specificity for a topB deletion mutator in which
      topoisomerase III is hampered. The frequency of supF- mutations in topB strain
      was 4.9 x 10(-7), that is essentially the same as that in wild-type strain, 3.1 x
      10(-7). Half the number of the supF- mutations were large deletions, where a
      specific deletion among a 10-base pair direct repeat dominated, but other types
      of deletions were also found. Most of the deletions were associated with the
      presence of directly repeated sequences capable of accounting for their
      endpoints. Frameshift mutations in topB strain also significantly increased
      compared with those of wild-type (17 vs. 2%). Base substitutions comprised 27% of
      the events, specificity of which in topB strain was the same as that in wild-type
      strain. The present data suggest that topB is a novel class of mutator that
      strongly induces repeated sequence dependent deletion mutagenesis and high
      frequencies of frameshift mutagenesis.

PMID- 9164484
TI  - Photoreversal of UV-potentiated glutamine tRNA suppressor mutations in excision
      proficient Escherichia coli.
AB  - UV-irradiated excision proficient Escherichia coli were exposed to light for
      photoenzymatic reversal (PR) of cyclobutane pyrimidine dimers (CPD) and assayed
      for reversion mutation (glutamine tRNA suppressor mutations) on semi-enriched
      medium or on the same medium containing acriflavine to inhibit excision repair.
      The initial mutation frequency without PR was relatively greater when assayed
      with acriflavine, and this difference increased as larger UV fluences were used.
      The PR kinetics were first order and about the same or slightly faster when cells
      were assayed with acriflavine (after 15, 30 or 45 J/m2, respectively). The
      results indicated mutation targeting by CPD in excision proficient cells. These
      results and conclusion contrast sharply with the original study of this type done
      several years ago. PR kinetics were considerably slower with assays containing
      acriflavine, sustaining the idea that PR causes repair of non-dimer targeting
      lesions by enhancing excision repair. To explain this contrast we devised a
      fluence-decrement rate for estimating the effectiveness of PR and measured PR
      dependent excision repair (PER) as the difference in the fluence-decrement rate
      with excision proficient and deficient cells. PER was more evident when cells
      were prepared as in the original study but was still an insufficient factor. More
      importantly, the original study included a component of indirect
      photoreactivation or photoprotection (using unfiltered PR light) which
      accentuated the role of excision repair. Taking these factors into account, the
      original data also are consistent with the model that glutamine tRNA suppressor
      mutations produced by UV-mutagenesis in excision proficient E. coli result from
      targeting by CPD just as in excision defective cells. Thus, with regards to a
      common UV mutation assay, there does not appear to be two types of targeting
      lesion depending on excision proficiency.

PMID- 9164485
TI  - Detection of MNNG-induced DNA lesions in mammalian cells; validation of comet
      assay against DNA unwinding technique, alkaline elution of DNA and chromosomal
      aberrations.
AB  - Human cells (VH10 or Hep G2) and hamster cells V79 were exposed to different
      concentrations of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and the level of
      DNA lesions was evaluated by the DNA unwinding technique, alkaline elution of DNA
      and the comet assay. All three methods were able to detect the effects of MNNG
      but with a clear difference in sensitivity. At low concentrations of MNNG the
      most sensitive method appeared to be the comet assay. After the short-term
      treatment the comet assay was able to detect the lesions induced by MNNG at
      approx. 0.1 microgram/ml, alkaline elution of DNA at 1 microgram/ml and DNA
      unwinding at 1-2 micrograms/ml. MNNG treated VH10 cells, human lymphocytes and
      V79 cells were also tested cytogenetically, confirming that MNNG induced
      chromosomal aberrations at concentrations > 1 microgram/ml in VH10 cells (short
      term treatment): > 0.2 microgram/ml in V79 cells (long-term treatment) and > 8
      micrograms/ml in human lymphocytes (long-term treatment). In some experiments we
      tried to increase the level of MNNG-induced DNA breaks with help of DNA repair
      inhibitors cytosine arabinoside (Ara C) and hydroxyurea (HU) which were applied
      either after or during MNNG treatment. Our results showed that the level of MNNG
      induced lesions was increased by simultaneous treatment of cells with MNNG and
      Ara C and HU. 2 x 10(-5) M Ara C and 2 x 10(-3) MHU were as effective as 10-times
      higher concentrations of inhibitors. Ara C and HU increased the level of MNNG
      induced DNA breaks mainly in combination with lower concentrations of MNNG (< 2
      micrograms/ml). Rejoining of DNA breaks was observed in human cells VH10 and Hep
      G2 as well as in Chinese hamster cells V79 damaged by both lower and higher MNNG
      concentrations. All methods showed that MNNG-induced DNA breaks had been
      gradually rejoined.

PMID- 9164486
TI  - [27th Annual meeting of the Austrian Society of Internal Medicine. September
      1996. Abstracts].

PMID- 9164487
TI  - American Society of Hypertension XIIth scientific meeting. May 27-31, 1997.
      Abstracts.

PMID- 9164488
TI  - The 10th International Conference on Antiviral Research. Atlanta, Georgia, USA,
      April 6-11, 1997. Abstracts.

PMID- 9164489
TI  - [4th Three-Country-Symposium of Biologic Psychiatry. Wurzburg, 10-12 October
      1996. Abstracts].

PMID- 9164490
TI  - 5th French-speaking Congress on Coelo-Surgery. Deauville, France, 10-11 April
      1997. Abstracts.

PMID- 9164491
TI  - [Annual meeting of the Berlin-Brandenburg Ophthalmology Association. 7-8 December
      1996, Berlin. Abstracts].

PMID- 9164492
TI  - [3rd Workshop of the German Association for Skull Base Surgery. Orbital surgery.
      Kiel, 8-9 November 1996. Abstracts].

PMID- 9164493
TI  - [German Society for Psychiatry, Psychotherapy and Neurology Congress 1996.
      Dusseldorf, 17-21 September. Abstracts].

PMID- 9164494
TI  - The 18th International Conference on Yeast Genetics and Molecular Biology.
      Stellenbosch, South Africa, March 31-April 5, 1997. Abstracts.

PMID- 9164495
TI  - [Disorders of myocardial perfusion--new aspects of diagnosis and therapy. 20th
      Fall meeting of the German Society for Cardiology and Cardiovascular Research.
      Giessen, 19-21 September 1996. Abstracts].

PMID- 9164496
TI  - Hepatolithiasis: epidemiology and classification.
AB  - Hepatolithiasis or intrahepatic stone is more common among East Asian countries
      than in Western world. The relative incidence (i.e. hepatolithiasis cases against
      all cases with gallstone disease) in the Western countries is approximately 1%
      whereas in Taiwan, South Korea, the People's Republic of China it has been
      reported to be 20%, 18% and 38-45% respectively. There are two types of
      hepatolithiasis and in East Asian countries one usually finds pigmented stone.
      The disease appears to be more common among people with low socio-economic
      status. No single worldwide accepted classification of hepatolithiasis exists at
      present.

PMID- 9164497
TI  - Morphology of intrahepatic duct in surgical treatment of hepatolithiasis.
AB  - BACKGROUND/AIMS: Surgery is the usual treatment for hepatolithiasis. However, the
      method of choice is based on intrahepatic duct morphology. MATERIAL AND METHODS:
      Six hundred sixty-two patients with hepatolithiasis were operated on in the
      period between 1980-1994. Hepatolithiasis was clinically classified into primary
      (75.8%) and secondary (24.2%) types. RESULTS: Patients treated between 1990-1994
      (35.9%), liver resection was performed in 71 patients (69 of left and 2 of the
      right liver). However, liver resection was chosen only in 6.7% (11/163) during
      the 1970s. Candidacy for liver resection increased recently due to the increase
      in primary type. According to the morphology of intrahepatic ducts, the location
      of stricture was classified into: Central type (n = 59, 30%), Segmental type (n =
      101, 51%), and Subsegmental type (n = 21, 10.6%), and unclassified (n = 17,
      8.4%). Liver resection was recommended for patients of segmental or subsegmental
      type. Choledocho-lithotomy with T-tube drainage was indicated in two third of the
      patients with hepatolithiasis. However, the incidence of post-operative retained
      stones was very high, and post-operative choledochoscopic lithotripsy was used to
      treat these post-operative problems easily. The mortality of this disease was 1%
      (2/198) in the 1990s compared with that of 4.1% (19/464) in 1980s and 10.1%
      (15/148) in 1970s. CONCLUSION: We strongly recommend that liver resection for
      patients with adequate indications will have good results. In addition, one
      should pay attention to the abnormal pattern of intrahepatic ducts that are
      commonly found in patients with hepatolithiasis during liver resection. Liver
      resection is an ideal surgical method for the eradication of diseased lesions and
      to prevent malignant changes from bile duct with stones. Concise information
      concerning the anatomic structure was found to be important in determining post
      operative results in the management of hepatolithiasis.

PMID- 9164498
TI  - Surgical treatment of hilar strictures in hepatolithiasis.
AB  - BACKGROUND/AIMS: The management of biliary strictures in hepatolithiasis,
      particularly at the hilus of the liver including the right and left hepatic bile
      ducts and their confluence, presents a challenge for surgeons because of their
      difficult access for surgical procedures and the life-threatening consequences,
      such as unrelenting cholangitis, recurrent biliary calculi, liver abscess and
      septicemia they can cause. This study analyzed the response of a group of
      patients with hilar strictures undergoing different surgical operations to assess
      methods dealing with this condition. PATIENTS AND METHODS: A total of 545
      patients with hepatolithiasis were admitted to our hospital. Among them, 256
      patients were found to have an association of high bile duct strictures. These
      were classified into three types based on the sites of the stricture, and
      operated on with different combined surgical procedures in accordance with the
      type of the strictures. After the operation, further assessment was made during a
      follow-up period of between 12 months to 6 years. RESULTS: Postoperative
      morbidity and mortality were 15.7% (40/256) and 1.2% (3/256), respectively.
      Before discharge from the hospital, all patients underwent imaging investigation,
      and the retained stone rate was 20.3% (53/256). Of the 70% of patients (179/256)
      who were available for further assessment, 85% had good treatment results, were
      asymptomatic and required no medical treatment. A few patients got a poor result
      when symptoms of cholangitis occurred several times a year and required
      hospitalization. CONCLUSIONS: Successful treatment of hilar strictures in
      hepatolithiasis depends on the correct localization of the strictures, and
      complete exposure of the biliary tract proximal to strictures as well as the
      appropriate selection of the surgical procedures.

PMID- 9164499
TI  - Current problems with intrahepatic bile duct stones in Japan--congenital biliary
      malformations as a cause.
AB  - BACKGROUND/AIMS: In patients with primary intrahepatic bile duct stones,
      strictures of the biliary duct are often present, but the relationship between
      these strictures and the formation of the stones remains controversial.
      Intrahepatic bile duct carcinoma in association with intrahepatic bile duct
      stones has recently been reported. The present study attempted to ascertain
      whether bile stasis induced by congenital biliary strictures is the basis for the
      formation of stones and occurrence of carcinoma. MATERIALS AND METHODS: We
      analyzed the location of strictures in 58 patients with strictures in the upper
      portion of the biliary tract including 38 patients with intrahepatic bile duct
      stones and 9 with intrahepatic bile duct carcinoma. The cell cycle of epithelial
      cells from the intrahepatic bile duct were analyzed with using proliferating cell
      nuclear antigen, which is a immunohistochemical staining method. RESULTS: Fifty
      six of 58 patients had congenital cystic dilatation of the common bile duct (two
      infant type and 54 adult type). Thirty eight patients had intrahepatic bile duct
      stones proximal to the strictures at the hepatic hilum. The location of the
      strictures were classified into four types. Nine patients had intrahepatic bile
      duct carcinoma and eight of the 9 carcinomas coexisted with intrahepatic bile
      duct stones. In the nine patients with intrahepatic bile duct carcinoma, the
      expression of proliferating cellular nuclear antigen (PCNA) in the carcinoma and
      the normal bile duct epithelium adjacent to the carcinoma was higher than that of
      patients with hepatocellular carcinoma without anomaly of the biliary duct.
      CONCLUSION: Considering the location of the strictures and clinical features, the
      strictures may have been formed congenitally. Furthermore, adult type cysts of
      the common bile duct with strictures in the upper portion of the biliary tract
      are thought to be the basis for the formation of primary intrahepatic bile duct
      stones. The most appropriate treatment for intrahepatic bile duct stones is thus
      suggested to be removal of the affected hepatic segment including the region of
      strictures, combined eventually with hepaticoenterostomy.

PMID- 9164500
TI  - Treatment of intrahepatic biliary stricture associated with hepatolithiasis.
AB  - Biliary stricture is a difficult complication in the management of
      hepatolithiasis. Resection of the hepatic segment containing biliary stricture(s)
      is ideal. Dilatation and stenting therapy with PTCSL in selective cases is a good
      adjuvant, sometimes alternative, therapy. We recommend a combination of
      multimodal treatment with a systemic approach to improve results. For recurrent
      or residual cases, PTCSL becomes the mainstay of treatment.

PMID- 9164501
TI  - Malignancy associated with hepatolithiasis.
AB  - BACKGROUND/AIMS: Malignancy is known to be associated with hepatolithiasis. The
      present report summarizes the results of our management of patients with
      cholangiocarcinoma associated with hepatolithiasis. MATERIALS AND METHODS: Twenty
      patients with cholangiocarcinoma and associated hepatolithiasis were analyzed
      retrospectively. There were 12 males and 8 females, with a mean age of 59.3
      years. The clinical records of these patients were reviewed to determine
      demographic characteristics, clinical features, laboratory findings, diagnostic
      tests, operative management and results of therapy. RESULTS: One patient was
      moribund on presentation and was treated conservatively. Fourteen patients
      underwent hepatic resection. Three of them had palliative resection. Hepatic
      resection was less likely to be performed in patients having right lobe disease
      (50%) as compared to patients having left lobe disease (90%) (p = NS). The
      overall operative morbidity and mortality rates after hepatic resection were 36%
      and 7%, respectively. Non-resective operations were performed in five patients.
      The overall operative morbidity and mortality rates after non-resective
      operations were 20% and 0%, respectively. After curative hepatic resection (11
      patients), the 1- and 2-year survival rates were 81% and 51%, respectively.
      CONCLUSIONS: A suspicion of malignancy is necessary in managing patients with
      hepatolithiasis. Hepatic resection is the treatment of choice for
      cholangiocarcinoma when it is resectable.

PMID- 9164502
TI  - Modern imaging in the evaluation of hepatolithiasis.
AB  - Hepatolithiasis is a primary disease of the biliary ducts, presenting with
      recurrent pyogenic cholangitis, complicated by parenchymal infection, obstructive
      cholangiopathy and subsequent parenchymal destruction. Cholangiocarcinoma is a
      rarer complication. Modern imaging aims at accurate delineation of biliary ducts
      and liver parenchyma. It directs planning of surgical or interventional
      treatment, and serves to guide these procedures. The characteristic features
      comprise varying combinations of ductal dilatation, intrahepatic/extrahepatic
      ductal stones, segmental ductal strictures and lobar/segmental atrophy; and in
      acute exacerbation parenchymal or ductal contrast enhancement, abscess and
      biliary obstruction. Ultrasonography is the preferred primary examination.
      Further imaging depends on the ultrasonography findings, the patient's
      symptomatology, the clinical problems and the intended mode of treatment.
      Contrast cholangiography is warranted preceding biliary intervention. Computed
      tomography evaluates ductal stones, extent of disease, acute parenchymal
      complications and prior to hepatic resection. Magnetic resonance imaging is less
      accessible, but obtains cross-sectional findings similar to computed tomography.
      It comprehensively evaluates the liver and portal venous system, for prognostic
      indication and contemplation of liver resection. For diagnostic purposes,
      magnetic resonance cholangiography promises to replace the more invasive contrast
      cholangiography. Therapeutic approaches tailored to the results of strategically
      applied imaging helps to improve the outcome of patients with hepatolithiasis.

PMID- 9164504
TI  - Pancreaticoduodenectomy for gallbladder cancer with peripancreatic nodal
      metastases.
AB  - The prognosis of patients with advanced gallbladder carcinoma remains dismal. In
      the English language literature, we found only one 5-year survivor with
      peripancreatic lymph node metastases. We herein report a patient with marked
      peripancreatic nodal metastases, who has exhibited the longest survival (6 years)
      without recurrence after a pancreaticoduodenectomy combined with extended
      cholecystectomy. This outcome suggests that pancreaticoduodenectomy may be
      effective for clearance of peripancreatic nodal metastases from gallbladder
      cancer.

PMID- 9164503
TI  - Biliary complications during and after laparoscopic cholecystectomy.
AB  - BACKGROUND/AIMS: Bile duct injury and bile leak are the most serious
      complications of laparoscopic cholecystectomy. The purpose of this study to
      present our experience in the management of biliary complications during and
      after laparoscopic cholecystectomy. MATERIAL AND METHODS: There were eight
      biliary complications (0.72%) in 1115 consecutive laparoscopic cholecystectomies
      during the period from January 1991 to December 1995. RESULTS: The biliary
      complications included: bile duct injuries in 3 patients, bile leak in 4 patients
      and malapplication of the endoclips on the common bile duct in patient. Three
      biliary complications were corrected by immediate conversion to laparotomy with
      good outcomes. Two patients with immediate postoperative bile leakage required
      laparotomy for religation of the cystic duct and one patient with delayed bile
      leakage was successfully corrected with conservative treatment. One common
      hepatic duct and right hepatic duct developed necrosis due to electrocoagulation
      and required a laparotomy with T-tube stent and had repeated attacks of
      cholangitis during the 21 month follow-up period. Another patient with common
      hepatic duct stricture due to endoclip injury needed re-laparotomy with T-tube
      stent and remained stationary over the 9 month follow-up period. CONCLUSION: Bile
      leak and bile duct injuries after laparoscopic cholecystectomy present a
      difficult surgical problem, surgical or endoscopic interventions are needed to
      correct the biliary problem after the diagnosis was established by the
      radiological image study.

PMID- 9164505
TI  - Reconstruction of the inferior vena cava using a hepatic venous patch obtained
      from resected liver.
AB  - A 59-year-old woman with a 3 cm liver metastasis from rectal cancer underwent an
      extended right hepatic lobectomy with partial resection of the wall of the
      inferior vena cava. The metastasis was located behind the roots of the right and
      middle hepatic veins and involved the inferior vena cava. For reconstruction of
      the inferior vena cava, the intrahepatic middle hepatic vein, 2.5 cm in length,
      which was distant from the metastatic lesion, was removed from the resected
      liver. Then divided longitudinally to prepare a venous patch of 2.5 by 2.0 cm in
      size and applied to the defect. This technique facilitates reconstruction of the
      inferior vena cava without sacrificing other veins.

PMID- 9164506
TI  - Modified Hill operation vs. Nissen fundoplication in the surgical treatment of
      gastro-esophageal reflux disease.
AB  - BACKGROUND/AIMS: The authors compared the results of the Nissen fundoplication
      technique with the results of the Hill procedure, by using a 10-year history of
      patients with gastro-esophageal reflux disease. MATERIALS AND METHODS: Seventy
      two consecutive patients entered the study, 32 of whom underwent a 360 degrees
      fundoplication according to Nissen and 40 with a modified Hill operation. In the
      Nissen Group, intraoperative manometry (IOM) was carried out in all patients; in
      the Hill Group, the patients were randomized in two sub-groups (A and B), before
      operation; in 20 of them (group A), the procedure was randomly associated to IOM.
      RESULTS: The overall complications were low in both groups (15.6% in the Nissen
      Group and 5% in the Hill Group, p = 0.1), and there was no mortality rate. The
      clinical results were excellent or good in 28 patients (87.6%) of the Nissen
      Group and in 36 patients (90%) of the Hill Group (p = 0.5); in particular, an
      excellent outcome was observed in 16 patients (80%) with IOM (sub-group A), while
      12 patients (60%) without it (sub-group B) showed similar results. The manometric
      studies carried out six months after surgical treatment showed a decrease of the
      lower esophageal sphincter pressures in all patients if compared to the pressure
      recorded intra-operatively. In comparison to the pre-operative values, both the
      lower esophageal sphincter length and its intra-abdominal portion were markedly
      increased in the Nissen Group and in the sub-group A of the Hill patients.
      CONCLUSIONS: These results support the conclusions that modified posterior
      gastropexy and 360 degrees fundoplication are effective, well tolerated, and can
      be properly used in the treatment of Gastro-esophageal reflux disease (GERD),
      since both techniques showed good clinical results. A favorable clinical outcome
      depends mostly on adequate lower esophageal sphincter length (LESL) and LESIA
      extension, which could be more efficiently achieved by the use of intraoperative
      manometry (IOM).

PMID- 9164507
TI  - Appleby operation for carcinoma of the body and tail of the pancreas.
AB  - Long-term survival of carcinomas in the body and tail of the pancreas after
      surgery is still rare. One of the major reasons for unresectability is cancerous
      invasion to major vessels, such as the common hepatic and splenic arteries.
      Resection of the involved arteries can increase resectability and thus might
      increase post-operative survival. The aim of this study was to clarify the
      importance of the Appleby operation for carcinoma of the body and tail of the
      pancreas. A Case Report was carried out with a 54 year-old man, had suffered back
      pain and loss of body weight for six months. Imaging procedures such as US, CT or
      angiography showed a carcinoma in the body of the pancreas, about 3 cm in size,
      and both the common hepatic and splenic arteries were invaded by the tumor. The
      Appleby operation was used for this patient, since firstly there was no invasion
      to the head of the pancreas, secondly neither the proper hepatic artery nor the
      SMA was involved, thirdly the root of the CA was free of carcinoma, and finally
      because clear pulsation of the proper hepatic artery could be felt one or two
      minutes after occlusion of the CHA, which indicated that resection of the CHA
      would not lead to hepatic ischemia. The postoperative course was uneventful. His
      appetite recovered well and his body weight increased to the level before the
      disease. The patient was relieved from back pain and has returned to work 18
      months after the operation, although he had a local recurrence eight months after
      the operation. In addition, eleven cases with carcinoma of the body and tail of
      the pancreas were used for a literature review. The average survival time after
      the Appleby operation is 6.6 months, and four patients are still alive. One
      patient has survived 13 years after the operation. It was concluded that although
      the prognosis after Appleby procedure is still not satisfactory that this
      operation can at least offer patients a better quality of life.

PMID- 9164508
TI  - The regrowth of rectal adenocarcinoma after pre-operative radiotherapy with a
      report of two cases.
AB  - To evaluate the factors that contribute towards the regrowth of rectal carcinoma
      after pre-operative radiotherapy. Of 120 patients, we pre-operatively treated
      with intraluminal brachytherapy or external beam radiotherapy since 1986, two
      showed regrowth of rectal carcinoma. For them, the case reports and findings for
      the resected specimen obtained using immunohistochemical staining for the P53
      tumor suppressor gene (P53) and proliferating cell nuclear antigen (PCNA) were
      retrospectively evaluated. The regrowth of rectal carcinoma was observed 40 days
      after intraluminal brachytherapy in one patient, and 33 days after external
      radiotherapy in the other. Both P53 and PCNA staining was seen in the recurrent
      tumors or during the examination of the resected specimen. These results suggest
      that polypoid tumors with regrowth have a malignant potential. The interval
      between radiotherapy and operation reported in the literature varies widely. The
      potential for regrowth should be considered in the preoperative radiotherapy for
      rectal cancer.

PMID- 9164509
TI  - Giant pedunculated liposarcomas of the esophagus: literature review and case
      report.
AB  - Although liposarcoma is the second most common soft-tissue sarcoma in adults, its
      incidence within the gastrointestinal tract is distinctly low. Esophageal
      involvement is exceedingly rare and only four cases have been described so far. A
      fifth case is presented here along with a thorough review of the literature of
      polypoid lipomatous tumors of the esophagus. Diagnostic and therapeutical
      strategies of these tumors are discussed in detail.

PMID- 9164510
TI  - Retractile mesenteritis: to treat or not to treat.
AB  - Retractile mesenteritis is a rare entity characterized by an inflammatory process
      of the mesenteric adipose tissue. The disease usually presents with abdominal
      pain or a palpable abdominal mass. In the majority of cases, the disease is self
      limiting and the prognosis is favorable. In this paper we describe a patient who
      presented with a 7 x 8 cm mass in the left upper abdomen, nausea and pain in the
      lower back. Symptomatic treatment was given with good result. The literature on
      different therapeutic intervention is briefly discussed.

PMID- 9164511
TI  - The effect of granulocyte colony-stimulating factor (G-CSF) on bacterial
      translocation in the splenectomized rat.
AB  - BACKGROUND/AIMS: We created a study group in order to investigate the effects of
      splenectomy and filgrastim. Filgrastim is an immunomodulator granulocyte colony
      stimulating factor (G-CSF), that affects bacterial translocation. MATERIALS AND
      METHODS: We created 3 study groups with 30 male Sprague-Dawley rats; the first
      group included sham splenectomy, the second group was splenectomy, and the third
      group was splenectomy+ filgrastim group. RESULTS: The mean bacterial colony count
      of the cecum were 2.5 x 10(9) in group 1, 1.2 x 10(10) in group 2 and 3.5 x 10(9)
      in group 3. The differences between these groups were accepted as statistically
      significant. The mean counts of the terminal ileum were 1.1 x 10(9) in group 1,
      5.5 x 10(10) in group 2 and 2.5 x 10(10) in group 3. The p values of group 1-2
      were 0.036 (statistically significant) and 0.123 in groups 2-3) were not
      statistically significant. The mean counts of the liver were 0.2 x 10(4), 1 x
      10(10) and 3.4 x 10(5), respectively. In comparison of the groups the p values of
      the first and last 2 groups were found to be 0.047 (statistically significant).
      The mean counts of the mesenteric lymph node were 0.7 x 10(3), 1 x 10(10) and 0.9
      x 10(6) respectively. The p values were 0.343 for the first and the last 2 groups
      both. As they were above 0.05, they were not statistically significant. The
      degrees of liver Kupffer cell hyperplasia were (+) 40%, (+2) 50% and (+3) 10%
      (group 1), (+) 10%, (+2) 40% and (+3) 50% (group 2), (+2) 60% and (+3) 40% (group
      3) (p = 0.0039). The rates of the absence of pathology in mesenteric lymph nodes
      were 70% (group 1), 90% (group 2) and 100% (group 3) (p = 0.049). These findings
      were statistically significant. CONCLUSIONS: We found that splenectomy has
      activated the whole predisposing factors of bacterial translocation and created
      the latter itself. In addition, we showed that filgrastim, a recently widespread
      used G-CSF, decreases bacterial translocation significantly.

PMID- 9164512
TI  - A comparison of the prevalence of autoantibodies in individuals with chronic
      hepatitis C and those with autoimmune hepatitis: the role of interferon in the
      development of autoimmune diseases.
AB  - BACKGROUND AND OBJECTIVES: Viral hepatitis due to hepatitis C virus results in
      chronic liver disease in more than 70% of individuals infected with the virus.
      Hepatitis C virus is also thought to be the cause of autoimmune chronic
      hepatitis, type II. The only treatment for chronic hepatitis C is interferon
      (IFN). IFN is both an antiviral agent and an up regulator of the cellular immune
      system. The latter effect is non-specific. Thus, IFN diffusely activates the
      cellular immune system and can initiate new autoimmune diseases in patients
      treated with it. To determine the prevalence of autoantibodies in patients with
      chronic hepatitis C and in patients with autoimmune hepatitis and to determine
      the incidence of new onset autoimmune disease in IFN-treated subjects with
      chronic hepatitis C, the records of 323 unselected patients with chronic
      hepatitis were reviewed. MATERIAL AND METHODS: A total of 203 patients with a
      mean age of 45.7 +/- 0.8, ranging 18-81 with either HCV disease or autoimmune
      hepatitis, were identified and studied. One hundred sixty-two patients with
      chronic hepatitis C defined by elevations of serum alanine aminotransferase (ALT)
      for at least 6 months, the presence of detectable anti-HCV (HCV; second
      generation enzyme immunoassay [EIA2], a positive recombinant immunoblot assay
      [RIBA], the presence of HCV-RNA by PCR in serum and an abnormal biopsy consistent
      with chronic hepatitis C) were identified. Each was also negative for HbsAg,
      HbeAg and anti-Delta. Forty-one patients with a putative autoimmune chronic
      hepatitis (AIH) diagnosed on the basis of serologic positivity for classical
      autoantibodies (ANA and anti-smooth muscle antibodies), tissue typing (B8, Dr3
      positive), characteristic liver biopsy findings and the absence of anti-HCV and
      HCV-RNA in serum were identified. The records of both of these groups of patients
      were reviewed for the following antibodies: anti-nuclear antibodies (ANA),
      antimitochondrial antibodies (AMA), anti-liver-kidney microsomal antibody (LKM),
      anti-smooth muscle antibodies (SMA), anti-microsomal antibodies (MSA). RESULTS:
      The rate of ANA positivity was 63% in both groups; the rate of SMA positivity was
      65% in patients with HCV infection (group I) and 63% in patients with AIH (group
      II). AMA was positive in 4% of the subjects in group I and 50% of the subjects in
      group II; anti-LKM antibodies were absent in all 91 HCV cases and were present in
      4% of the cases in group II; MSA positivity was present in 17% of group I and 10%
      of group II. Eighty-one of the one hundred sixty-two patients (50%) with chronic
      hepatitis C received IFN treatment at a dose of 5 MU SQ daily for 6 months.
      Thirty-two of these eighty-one patients (42 females and 39 males with a mean age
      of 45.0 +/- 1.3, ranging from 18 to 81 yr.) had at least two autoantibodies
      detectable prior to the IFN therapy (subgroup 1) and 49 had one or no
      identifiable autoantibodies (subgroup 2) present prior to IFN therapy. No
      significant differences in the interferon response rate defined by HCV-RNA
      negativity and normalization of serum ALT levels at the end of therapy was noted
      between those with autoantibodies and those without autoantibodies. Fifteen of
      the interferon-treated patients developed a clinical manifestation of a new onset
      autoimmune disease during the course of their interferon treatment. Six of the
      fifteen patients belonged to subgroup 1 (n = 32) and the remaining 9 patients to
      subgroup 2 (n = 49) (p > 0.05). None were managed by discontinuing the
      interferon. Most required some form of specific treatment.(ABSTRACT TRUNCATED)

PMID- 9164513
TI  - Effects of propylthiouracil on intestinal transit time and symptoms in
      hyperthyroid patients.
AB  - BACKGROUND/AIMS: Gastrointestinal disturbances such as diarrhea and malabsorption
      with steatorrhea may show up in hyperthyroid patients. The aim of our study was
      to evaluate oro-caecal transit time (OCTT) and gastrointestinal symptoms in
      hyperthyroid patients before and after propylthiouracil administration. MATERIALS
      AND METHODS: Twenty hyperthyroid patients (15 Females and 5 Males, mean age 47
      years) were studied. Eight of them had diarrhea and 10 steatorrhea. The control
      group was composed of 20 healthy volunteers (13 F and 7 M, mean age 49 yrs). OCTT
      and fecal fat excretion were measured before and after propylthiouracil
      administration (300 mg/day for 10 day and then 200 mg/day for 30 days). RESULTS:
      Before the treatment in hyperthyroid patients had began the mean OCTT was
      significantly lower than in the control group (64 min. versus 107 min; p <
      0.0001). After treatment mean OCTT became similar to the controls (p = ns);
      diarrhea disappeared in all affected patients and mean fecal fat excretion was
      reduced from 7.9 gr/24h to 3.4 gr/24h, with a statistically significantly
      difference (p < 0.0001). CONCLUSIONS: The treatment with propylthiouracil induces
      the normalization of thyroid hormone status and consequently of OCTT with the
      disappearance of gastrointestinal symptoms, such as diarrhea and steatorrhea,
      with a better efficacy if compared to other drugs utilized in the treatment of
      hyperthyroidism.

PMID- 9164514
TI  - Prognostic value of the TNM-classification for small bowel cancer.
AB  - BACKGROUND/AIMS: To examine the relationship between the pathological stage and
      survival for adenocarcinoma of the small bowel. MATERIALS AND METHODS: The
      medical records of 99 patients with small bowel cancer, diagnosed between January
      1984 and December 1993, were reviewed retrospectively. Lymphomas and carcinomas
      of the ampulla of Vater were excluded from this study. All operated patients with
      adenocarcinomas were staged by the TNM-classification using pathological and
      surgical reports. RESULTS: Sixty-four adenocarcinomas, 24 carcinoid tumours and
      11 sarcomas were analysed. The cancer-specific 5-year survival rate for patients
      with adenocarcinoma, carcinoid tumours and sarcomas was 22%, 39% and 55%,
      respectively. Twenty-eight patients with adenocarcinoma underwent radical tumor
      resection: segmental resection in 20, pancreaticoduodenectomy in 7 and ileocoecal
      resection in one patient. In the remaining 34 patients "curative" resection was
      not feasible and none of them survived for more than 3 years. The 5-year survival
      rate of the curatively resected patients was 46%. Actuarial 3-year survival rate
      for stage I was 38%, 70% for stage II and 0% for stage III. CONCLUSION: Our
      results demonstrate that survival is poor for patients with lymph node
      metastasis, despite apparently curative surgery.

PMID- 9164515
TI  - Differential activation of total and EGF receptor (EGF-R) tyrosine kinase (tyr-k)
      in the rectal mucosa in patients with adenomatous polyps, ulcerative colitis and
      colon cancer.
AB  - BACKGROUND/AIMS: Tyrosine kinase and a number of growth factors, especially EGF
      and TGF-alpha are known to stimulate proliferation in much of the
      gastrointestinal tract, including colon. In humans increased colonic mucosal
      proliferative activity has been observed in numerous premalignant lesions
      including adenomatous polyps and ulcerative colitis. The aim of the present study
      was to determine the differences of proliferative patterns in patients with
      adenomatous polyps, ulcerative colitis and colonic adenocarcinoma as reflected by
      rectal mucosa tyrosine kinase, EGF receptor tyrosine kinase and PCNA and to
      evaluate the role of tyr-k in colonic mucosal cell proliferation during
      carcinogenic process. MATERIALS AND METHODS: The study population comprised 40
      patients, aged 17-74 years (mean 57), in which 10 patients had adenomatous
      polyps, 10-ulcerative colitis in remission phase, 10- colon adenocarcinoma and 10
      healthy controls. After informed consent 6-8 rectal mucosal biopsy specimen were
      obtained at 10 cm from the anal verge at the beginning of the colonoscopy
      examination and at least 10 cm away from any macroscopic mucosal changes.
      RESULTS: Mean PCNA labeling indices in patients with colon adenocarcinoma,
      adenomatous polyps, ulcerative colitis ulcerosa and healthy controls were
      respectively: 27.6% +/- 5.75; 12.18% +/- 6.76; 10.9% +/- 5.34 and 1.5% +/- 0.97.
      PCNA labeling index in rectal mucosa of patients with adenomatous polyps,
      ulcerative colitis and colon cancer was significantly higher (p < 0.01) than in
      the control group. An upward expansion of the proliferative compartment was also
      observed in patients with premalignant and malignant colon conditions as regards
      to the control group. Total tyrosine kinase activity in the rectal mucosa of
      patients with polyps was elevated by 219%, with ulcerative colitis by 224% and
      with colorectal carcinoma by 600% as regards to the control group. EGF receptor
      tyrosine kinase was increased in colonic mucosa by 35.2% in patients with
      adenomatous polyps, by 40.6% in patients with ulcerative colitis and by 123% in
      patients with colon cancer. CONCLUSIONS: Increased values of this enzyme in the
      above mentioned group of patients may suggest that tyrosine phosphorylation
      represents an early sign of colonic mucosa susceptibility for cancer development.
      We conclude, that overall an EGF receptor-associated tyrosine kinase plays an
      important role in the development of hyperproliferative state of the colonic
      mucosa and colon carcinogenesis.

PMID- 9164516
TI  - Cancer of the colon and rectum in the first three decades of life.
AB  - BACKGROUND/AIMS: Recently an increasing number of young colorectal carcinoma
      patients attending the University Hospital, Kuala Lumpur were noted. This report
      represents our experience with patients suffering from colorectal cancer aged 30
      years or younger. MATERIALS AND METHODS: All cases of primary carcinoma of the
      colon and rectum admitted to the University Hospital during 1990 to 1994 were
      respectively reviewed. Inclusion criteria was that the patient had been 30 years
      or younger. Data collected included age, gender, race, site of tumour, presenting
      symptomatology, duration of symptoms, histology, extension of tumour and nodal
      involvement predisposing factors, treatment and follow-up. RESULTS: 21 patients
      were included, 5 patients (24%) were 30 years old at diagnosis, 12 (57%) patients
      were aged 20-29 years and 4 patients (19%) were less than 20 years old. Thirteen
      of the 21 patients were female, and 8 (38%) were male, 6 of the 21 patients (29%)
      were Malaysian, while 1 was Indian (4%). The remainder were Chinese, 14 patients
      (67%). Six patients (29%) had their primary tumour located in the rectosigmoid, 4
      (19%) in the left colon, 1 (4%) in the splenic flexure, 2 in the transverse colon
      (9%), 1 in the hepatic flexure (4%) and 5 in the caecum 24(%). One patient had a
      tumour too diffuse to detect a primary site at the time of operation. One patient
      with a family history of polyps had his entire colon removed at age 14. He had 3
      separate foci of tumour. The 5-year survival rate was 25%. DISCUSSION: Most
      patients with extensive disease and mucinous histology. Lesions are commonly seen
      beyond the transverse colon (57%). Presentation included most commonly abdominal
      pain, haematochezia or haemoccult positive stools. CONCLUSION: The symptoms above
      should alert surgeons to colorectal carcinoma as a differential diagnosis.

PMID- 9164518
TI  - Metastatic potential of colorectal adenoma containing carcinoma determined by pre
      operative assessment of morphology.
AB  - BACKGROUND/AIMS: Colectomy with lymphadenectomy is sometimes considered to be the
      appropriate management for patients with colorectal carcinoma in adenoma invading
      beyond the muscularis mucosa. Our study was done to determine whether gross
      features of the tumor would provide information to predict the metastatic
      potential. MATERIAL AND METHODS: Thirty one carcinomas in adenomas from 29
      patients were surgically resected. Macroscopic findings with regard to size and
      morphologic type were compared with the presence or absence of lymph node
      metastasis and vessel invasion. RESULTS: The rate of lymph node metastasis in all
      cases was 20.0% (6/30). Lymphatic and venous invasion was also identified in 7
      (22.6%) and 5 (16.1%) cases, respectively. There was no evidence of nodal
      involvement in pedunculated lesions, but the incidence of nodal involvement was
      18.8% and 60.0% in sessile and protruded tumors, respectively. There was a
      significant correlation between morphologic type and the incidence of lymph node
      metastasis. The mean size of node positive tumors was 5.9 cm with a range of 3.8
      9.0 cm, that is significantly larger than the value of 3.8 cm in cases of node
      negative tumors. All the node positive tumors exceeded 3.5 cm. With adjustment
      made for the morphology, the estimated risk of nodal involvement of tumors with a
      sessile shape and larger than 3.5 cm was 33.3%. Therefore, both large sessile and
      protruded types mean a high risk for lymph node metastasis. CONCLUSIONS:
      Macroscopic features, size and gross type are critical factors in determining the
      metastatic potential of carcinoma in colorectal adenoma. We recommend segmental
      colectomy with lymphadenectomy for such patients.

PMID- 9164517
TI  - Treatment of active and postactive ileal and colonic Crohn's disease with oral pH
      modified-release budesonide. German Budesonide Study Group.
AB  - BACKGROUND/AIMS: Budesonide is a glucocorticoid with a high topical anti
      inflammatory but low systemic activity due to its rapid hepatic inactivation. The
      aim of this open, multicenter study was to investigate efficacy and safety of
      oral pH-modified-release budesonide in patients with active Crohn's disease of
      the ileum and colon and in maintaining budesonide-induced remission in postactive
      Crohn's disease. MATERIALS AND METHODS: 81 patients (intention-to-treat) received
      3 x 3 mg budesonide/day for 6 weeks, followed by 3 x 2 mg budesonide for another
      6 weeks in case of response to initial treatment. Clinical and laboratory
      parameters were assessed at study entry as well as after 2, 4, 6 and 12 weeks of
      treatment. RESULTS: On an intention-to-treat basis remission was induced in 54.3%
      of 81 patients with active Crohn's disease, 71.4% of 35 patients stayed in
      remission after the acute-phase treatment until the end of the trial. Typical
      steroid-related side effects were observed during the acute-phase treatment in
      only 18% of the patients. Duration, severity and extent of disease at study entry
      played no significant role in the outcome of the trial, but there was a tendency
      towards better results during the acute-phase treatment in patients with moderate
      disease activity and affection of the terminal ileum and proximal colon.
      CONCLUSIONS: Budesonide could be an alternative to conventional steroid treatment
      in patients with active Crohn's disease.

PMID- 9164519
TI  - Mechanically stapled esophagojejunostomy. Results of a prospective series of 176
      cases.
AB  - BACKGROUND/AIMS: To evaluate the reliability of stapled esophagojejunostomy.
      MATERIAL AND METHODS: We studied a non-selected prospective series of 176
      consecutive total gastrectomies (169 cancers, 7 benign pathologies). RESULTS:
      Hand-sewn esophagojejunostomy was performed 5 times after failure of the stapled
      esophagojejunostomy. There were fourteen hospital deaths (8%), and 63 patients
      (36%) presented complications. There were 5 anastomotic leaks (2.8%) but non were
      responsible for deaths. In these 5 cases, there had been an incident during
      construction of the esophagojejunostomy. Such an incident was the only
      significant risk factor for an anastomotic leak: 17% after an incident and 0% in
      the absence of an incident (p < 0.001). We observed no cases of anastomotic
      stricture. CONCLUSION: Stapled esophagojejunostomy is a reliable technique when
      technical precautions are taken. It is easier to reproduce than hand-sewn
      esophagojejunostomy and has demonstrated low specific morbidity and no direct
      mortality.

PMID- 9164520
TI  - Repeated injection sclerotherapy is preferable to combined therapy with variceal
      ligation to avoid recurrence of esophageal varices:--a prospective randomized
      trial.
AB  - BACKGROUND/AIMS: The aim of this prospective randomized study is to investigate
      the safety, efficacy, complications and recurrence of varices after repeated
      endoscopic injection sclerotherapy (EIS), and combined therapy of endoscopic
      variceal ligation (EVL) and repeated EIS, for the treatment of esophageal
      varices. MATERIAL AND METHODS: Sixty-one consecutively treated cirrhotic patients
      were examined. Thirty patients were placed randomly in the EIS group and the
      other 31 in the EVL+EIS group. For the EIS group, EIS was repeated at weekly
      intervals using 5% ethanol- amine oleate (EO) until all the varices had been
      eradicated. In the EVL+EIS group, EVL was done at the initial session, then EIS
      was repeated at weekly intervals from one week after EVL. RESULTS: There was no
      significant difference between the EIS and EVL+EIS groups with regard to the rate
      of eradication (80.0% vs 74.2%), the total number of treatment (4.1 +/- 0.8
      sessions of EIS vs EVL and 3.0 +/- 0.5 sessions of EIS) and hospitalization time
      (4.9 +/- 1.6 vs 4.4 +/- 1.0 weeks). The total volume of EO used for the EVL+EIS
      group was significantly less than that for the EIS group (26.3 +/- 8.3 vs 47.1 +/
      11.6 ml, p < 0.01) and the incidence of minor complications at the initial
      treatment in the EVL+EIS group was significantly (p < 0.01) lower than that in
      the EIS group. Follow-up endoscopy showed that the rate of attaining
      circumferential ulceration and the following fibrotic scarring in the EVL+EIS
      group was significantly lower than that in the EIS group (21.7% vs 91.7%, p <
      0.01) and that the incidence of variceal recurrence was significantly higher in
      the EVL+EIS group than in the EIS group (39.1% vs 8.3%, p < 0.05) over a median
      follow-up of 12.3 months. CONCLUSION: The combined therapy of EVL and repeated
      EIS seems favorable from the viewpoint of fewer complications, but repeated EIS
      is preferable to combined therapy to avoid recurrence of the esophageal varices.

PMID- 9164521
TI  - Does a long pre-operative hospital stay before hepatectomy improve liver
      dysfunction in HCC patients with chronic liver disease?
AB  - BACKGROUND/AIMS: We retrospectively evaluated whether or not hepatic dysfunction
      improved in patients with chronic liver disease who had been waiting to undergo a
      hepatectomy after admission. MATERIALS AND METHODS: Fifty-two hepatocellular
      carcinoma patients had been admitted for more than 2 weeks prior to undergoing a
      hepatectomy. They had a liver function test twice, at admission and just before
      surgery, during the hospitalization period. Twenty-six of them were
      histologically diagnosed as having chronic hepatitis while the remainder had
      liver cirrhosis. In the liver function test, the serum levels of albumin, total
      bilirubin, glutamic pyrubic transaminase (alanine transaminase), total
      cholesterol and the Child grade were examined. RESULTS: First, including the pre
      operative treatment cases for small tumors under angiography, the total bilirubin
      and transaminase levels improved in the chronic hepatitis patients with a
      statistically significant difference, but no difference was observed in the Child
      grade. In the examined cirrhotic patients, no significant difference was shown in
      the tests. Second, after excluding the pre-operative treatment cases, we
      performed the same investigation as that for chronic liver disease cases and only
      the transaminase level significantly improved. CONCLUSIONS: A long pre-operative
      hospital stay might only by justified in patients with a high level of
      transaminase corresponding to chronic active hepatitis.

PMID- 9164522
TI  - Circulating intercellular adhesion molecule-1 in patients with hepatocellular
      carcinoma before and after hepatic resection.
AB  - BACKGROUND/AIMS: We recently demonstrated that an activated inflammation in a non
      tumorous portion was a significant risk factor for recurrence in patients with
      small hepatocellular carcinoma. The purpose of this study is to provide further
      proof for this mechanism by explaining the relation ship between the post
      operative hepatitis state and intrahepatic recurrence. PATIENTS AND METHODS: We
      used an enzyme-linked immunosorbent assay to detect cICAM-1 in the serum of 18
      patients with hepatocellular carcinoma before and after hepatic resection.
      RESULTS: A complete surgical resection of the tumor masses did not result in a
      significant reduction of cICAM-1 levels. The levels of aminotransferase after
      hepatic resection in patients with an increased level of cICAM-1 in the post
      operative period (n = 7) were much higher than in patients with a decreased level
      of cICAM-1 (n = 11) (p < 0.05). The 1-, 2- and 3- year disease free survival
      rates in the former group were 42.9%, 14.3% and 0%, respectively, and those in
      the later group were 72.7%, 54.5% and 54.5%, respectively (p < 0.05).
      CONCLUSIONS: The enhancement of inflammation in the remnant liver tissue is
      related to intrahepatic recurrence after hepatic resection through adhesion
      molecules, such as cICAM-1.

PMID- 9164523
TI  - Parameters predicting response to alpha-interferon treatment in chronic hepatitis
      C.
AB  - BACKGROUND/AIMS: Sustained response to alpha-interferon treatment for chronic
      hepatitis C is seen in only 25% of cases. Therefore, it is desirable to define
      pretreatment factors predicting responders. MATERIALS AND METHODS: Forty-nine
      patients with chronic hepatitis C were treated with a standard alpha-interferon
      regimen (3 x 3 MU s.c./week). Demographic, biochemical and immunological
      parameters, and HCV genotypes were obtained prior to initiation of treatment and
      evaluated for their value in predicting response to alpha-interferon therapy.
      RESULTS: Response, as defined by normalization of ALT, was 71% during interferon
      therapy and sustained response after discontinuation of interferon 24.5%.
      Patients infected with HCV-genotype 1b had significantly more often "community
      acquired" disease. Their outcome was worse with a response rate of 44% during
      therapy and a sustained response of 12.5%, as compared to 87% and 27%
      respectively in patients infected with genotypes other than 1b. On multivariate
      analysis, absence of cirrhosis, HCV-genotype other than 1b, higher ALT levels and
      higher numbers of CD8 positive liver infiltrates were found to be predictors of
      response during alpha-interferon therapy. CONCLUSION: Response to alpha
      interferon therapy seems to be influenced both by viral virulence factors and by
      the intensity of the host immune response to HCV.

PMID- 9164524
TI  - Modified Sugiura's procedure may improve liver function in portal hypertension.
AB  - BACKGROUND/AIMS: Sugiura procedure is an alternative in the treatment of the
      bleeding gastroesophageal varices. The postoperative alterations of CT and
      biochemical features versus pre-operative levels in patients operated on for
      haemorrhagic portal hypertension were studied. MATERIAL AND METHODS: Eight
      patients with liver cirrhosis and portal hypertension who underwent emergency or
      elective modified Sugiura's operation, were included in this study. The hepatic
      function and the CT scan ratio of transverse caudate lobe width to transverse
      right lobe width, pre-operatively and during the early and late postoperative
      period were studied. RESULTS: The hepatic function was aggravated during the
      immediate postoperative period but was remarkably improved, versus pre-operative
      status, after the first 15-30 postoperative days. The caudate to right lobe ratio
      from 0.66-1.7 pre-operatively, decreased to < 0.65 in all cases after the first
      postoperative month or year. One patient died on the 64th postoperative day from
      progressive hepatic failure, while all tests of the first postoperative month
      follow-up were improved. Another patient presented a light rebleeding 4 years
      after operation, while the hepatic tests were average. CONCLUSIONS: The modified
      Sugiura's procedure is an effective procedure in the disappearence of the
      oesophageal varices, followed by low mortality and low recurrent bleeding, but it
      mainly leads to an improvement of the hepatic function, probably due to improved
      hepatic portal blood flow.

PMID- 9164525
TI  - Radical surgery for liver hydatid disease: a study of 89 consecutive patients.
AB  - BACKGROUND/AIMS: This study was designed to evaluate the effectiveness of radical
      surgery for liver hydatid disease. MATERIALS AND METHODS: Hospital charts of 104
      consecutive patients with liver hydatidosis observed in our unit during the
      period 1982-1994 were reviewed. A total of 121 cysts in 89 patients were treated
      surgically: with cystopericystectomy in 66 and liver resection in 23. RESULTS:
      The overall incidence of postoperative complications was 19%: 19.7% and 17.1%
      after cystoperi-cystectomy and liver resection respectively (p = 0.32). Overall
      postoperative mortality was 1%. Among the 72 patients available for follow-up,
      only one (1%) had a local recurrence of the disease. CONCLUSIONS: Results suggest
      the safety and efficacy of radical procedures in the surgical management of liver
      hydatid disease. Total cystopericystectomy is the treatment of choice but liver
      resection is justified in selected cases.

PMID- 9164526
TI  - Effects of biliary obstruction on hepatic deoxyribonucleic acid and protein
      synthesis after partial hepatectomy.
AB  - BACKGROUND/AIMS: Major hepatectomy for biliary malignancy associated with biliary
      obstruction is often complicated due to hepatic failure. To determine the effects
      of biliary obstruction on liver regeneration, hepatic deoxyribonucleic acid and
      protein synthesis after partial hepatectomy was studied in rats with pre
      operative biliary obstruction. MATERIALS AND METHODS: After 5 or 14 days of
      biliary obstruction, experimental rats underwent concurrent biliary decompression
      and 70% partial hepatectomy. Control rats underwent partial hepatectomy alone.
      Hepatic deoxyribonucleic acid synthesis was determined 24 hours after partial
      hepatectomy. Hepatocellular protein synthesis and secretory protein synthesis
      were determined at baseline and 48 hours after partial hepatectomy. RESULTS:
      Deoxyribonucleic acid synthesis was significantly depressed in rats with biliary
      obstruction compared with controls (p < 0.05). Baseline hepatocellular protein
      synthesis and secretory protein synthesis, especially secretory protein
      synthesis, increased in proportion to the duration of biliary obstruction (p <
      0.01). After partial hepatectomy, control rats showed marked increases in
      hepatocellular protein synthesis and secretory protein synthesis (p < 0.01).
      Increased baseline hepatocellular protein synthesis and secretory protein
      synthesis were preserved in the regenerating liver of rats with biliary
      obstruction. CONCLUSIONS: The results suggest that biliary obstruction gives
      priority to secretory protein synthesis over DNA synthesis which may inhibit
      liver regeneration.

PMID- 9164527
TI  - Early detection of recurrent hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Early detection and treatment of recurrent hepatocellular
      carcinoma (HCC) are keys to patient survival after hepatic resection. In attempts
      at early detection, we make use of the alpha-fetoprotein (AFP) test every month
      and abdominal ultrasound (US) and computed tomography (CT) are carried out every
      three months after hepatectomy. The objective of the present study was to
      evaluate the most appropriate interval for follow-up re-examinations after
      resection for HCC. PATIENTS AND METHODS: Eighty-five patients with recurrent HCC
      were divided into two groups according to the state of the tumor when recurrence
      was detected: Group I (n = 70); tumor size < or = 2.0 cm, and group II (n = 15);
      tumor size > or = 2.1 cm. Clinicopathological comparisons were made between the
      two groups. RESULTS: AFP positivity in group I was significantly lower than group
      II at the time of recurrence. Rates of extrahepatic intra-abdominal recurrences,
      i.e. recurrence at the surgical stump and in the abdominal cavity and lymph nodes
      around the liver, were more frequent in group II than in group I (47% vs 4%; p <
      0.001). The average tumor size was larger in 10 patients with extrahepatic intra
      abdominal recurrence than in 75 patients with intrahepatic recurrence (3.4 +/-
      2.0 vs 1.6 +/- 0.6 cm; p < 0.0001). There was a statistically significant
      difference regarding the histological grade of initial HCC between the two
      patterns of recurrence. CONCLUSIONS: Measurements of AFP were seen to have
      limited value for detecting recurrence, at an early stage. Close postoperative
      follow-up, including bedside US in the outpatient clinic, should be carried out
      when the initial HCC is histologically less differentiated HCC.

PMID- 9164529
TI  - Biloma and biliary fistula associated with hepatorrhaphy for liver injury.
AB  - BACKGROUND/AIMS: To review our experience in managing post-hepatorrhaphy
      complications in liver trauma. MATERIALS AND METHODS: During the period of 1986
      1994, 6250 trauma patients were admitted to the Accident & Emergency Unit of the
      University Hospital Kuala Lumpur. The medical records were reviewed. There were
      175 patients with liver trauma requiring hepatorrhaphy. The major post-operative
      complications (biloma and biliary fistula) were noted. We reviewed and discussed
      the various management of these biliary complications. RESULTS: Eleven patients
      developed either a biloma, biliary fistula or both. Patients age ranged from 15
      to 40 years with a mean ISS of 23. Seven patients suffered penetrating injury and
      4 were victims of blunt trauma. The right lobe was injured in 10 patients, with 1
      patient sustaining left lobe injury. All liver injuries were either grade 3 (7
      patients) or grade 4 (4 patients). No patient sustained extrahepatic biliary
      tract injury. Biloma and fistulas were diagnosed 14-30 days post-injury (mean 24
      days) by CT or HIDA scans. All were managed by CT-guided percutaneous drainage.
      One patient also required percutaneous transhepatic cholangiography with biliary
      stent placement due to bile-stained ascites. Fistulas persisted from 5-120 days
      (mean 44 days). No patient required further operative intervention all fistula
      closed spontaneously without complication. CONCLUSION: Uncomplicated biliary
      fistula post-hepatectomy for liver trauma can be treated with percutaneous
      drainage.

PMID- 9164528
TI  - Right hepatic lobectomy in elderly patients with hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: The outcome of hepatectomy in elderly patients with
      hepatocellular carcinoma have been reported, however neither the morphological
      nor functional hepatic regeneration in elderly patients have been fully
      investigated. MATERIALS AND METHODS: Fifty-six patients with hepatocellular
      carcinoma, who underwent a right hepatic lobectomy over an 8-year period, were
      classified into three groups according to their age; group 1 (n = 7), more than
      70 years of age; group 2 (n = 40), patients from 50 to 69 years of age and group
      3 (n = 9), under 50 years of age. There were no significant differences regarding
      backgrounds or intra-operative parameters among the three groups. The
      perioperative hepatic function, postoperative complications and the regeneration
      rate of the remnant left lobe at 1 month after operation were compared. RESULTS:
      No differences were found in the regeneration rate, however, the levels of the
      hepaplastin test and lecithin:cholesterol acyltransferase at 7 days after
      hepatectomy in group 1 (31.3%, 8.8 U) were significantly lower than those in
      groups 2 and 3 (37.4%, 18.4 U; 47.9%, 29.4 U, respectively). The incidence of
      hospital death due to hepatic failure in group 1 (42.9%) was also significantly
      higher than that of group 2 (5.0%) or group 3 (0%). CONCLUSION: The decline of
      postoperative protein synthesis regardless of the voluminal regeneration is a
      characteristic of the elderly. This phenomenon might thus be an important
      promoter of postoperative hepatic failure which remains unpredictable using any
      type of examination. Therefore, at this time, a major hepatectomy is not
      recommended as a viable treatment alternative in the elderly.

PMID- 9164530
TI  - Transcatheter arterial chemoembolization in cytoreduction of inoperable
      hepatocarcinomas.
AB  - Transcatheter arterial chemoembolization (TAE) is often considered a mean of
      palliation for inoperable liver carcinomas. A few centers use a sequential
      treatment (TAE followed by surgery). However the role of TAE in bringing to
      surgery patients with hepatocarcinomas (HCC) considered inoperable at first
      diagnosis is debated. We report on the case of a 57 y.o. male diagnosed as having
      HCC, inoperable because of bilateral location and size. The patient was treated
      with repeated TAEs and the results were monitored with CT scans. After three
      TAEs, the main tumor mass volume was reduced 2.2 fold and the patient could
      undergo surgery; the postoperative period was uneventful, with no clinical signs
      of liver failure. Our experience leads us to suggest that TAE, further to being
      an option for palliation, can be a valuable tool to lead to surgery otherwise
      inoperable HCC patients.

PMID- 9164532
TI  - Intrahepatic hematoma with secondary Salmonella infection via biliary fistula.
AB  - Usually liver hematoma after blunt trauma is treated conservatively as long as
      clinically possible, in order to avoid infection via drainage. We report a
      patient who developed a huge liver abscess after a minor blunt trauma caused by a
      piece of wood that hit his hepatic region during work with a circular saw.
      Neither conservative treatment nor percutaneous drainage was successful and
      intraoperatively a biliary fistula was identified as the route of infection by
      salmonella. Cholecystectomy (here meaning removal of the salmonella reservoir)
      and consequent drainage of the gall flow via T-drain were the crucial therapeutic
      steps and the fistula finally closed after three months. Therapeutic
      possibilities in the management of blunt liver trauma, and biliary and septic
      complications are discussed.

PMID- 9164531
TI  - Interferon treatment of porphyria cutanea tarda associated with chronic hepatitis
      type C.
AB  - We evaluated the efficacy of interferon in the treatment of a 61 year-old male
      patient with porphyria cutanea tarda associated with hepatitis C virus infection.
      After initiation of intravenous administration of interferon-beta, urinary
      excretion of uroporphyrin and coproporphyrin, serum transaminase, gamma-glutamyl
      transpeptidase levels and ferritin were gradually increased. However, after
      completion of interferon-beta administration for 6 weeks, urinary excretion of
      uroporphyrin and coproporphyrin, serum enzymes and ferritin were significantly
      decreased correspondent with diminished hepatitis C virus RNA titer. These
      results suggest that interferon may be beneficial for the treatment of porphyria
      cutanea tarda due to hepatitis C virus infection.

PMID- 9164533
TI  - Predictors of the early development of advanced metachronous colon adenomas.
AB  - BACKGROUND/AIMS: In order to reduce the number of colonoscopies performed for the
      surveillance of patients after polypectomy, suitable predictors of adenomas
      recurrence are needed. The aim of this study was to find predictors of the early
      development of metachronous adenomas and specifically of advanced ones. MATERIALS
      AND METHODS: Forty-four patients underwent total colonoscopy 24-26 months after
      initial endoscopic polypectomy. All polyps were endoscopically removed and an
      adenoma was considered as advanced if the diameter was > 1 cm and/or villous
      component and/or severe dysplasia were present. RESULTS: Metachronous adenomas
      were detected in 16 (36.4% patients. Five (11.4%) of them had advanced
      metachronous adenomas. Early recurrence of adenomas was significantly correlated
      with the total number of indices adenomas (p = 0.027). On the contrary, the
      presence of metachronous adenomas was not related to any of the patients'
      characteristics nor to the site and the histology of the indices adenomas. The
      development of advanced metachronous adenomas during the same period was
      significantly correlated with patients' age, as it was observed only in patients
      aged > or = 60 years (5/21 or 23.8%) and in none of the patients aged < 60 years
      (Odds ratio: 15.7, p = 0.02). Logistic regression analysis revealed that
      patient's age was the only significant predictor of the early development of
      advanced metachronous adenomas (beta = 0.40, p = 0.02) and that the number of the
      indices adenomas was the only significant predictor for the recurrence of all
      adenomas (beta = 1.59, p = 0.02). CONCLUSIONS: 1. Only patients aged > or = 60
      years seem to develop advanced metachronous adenomas two years after polypectomy
      and 2. The likelihood for developing metachronous adenomas during the same period
      is related to the number of indices adenomas.

PMID- 9164535
TI  - Overexpression of p53 is associated with growth pattern and prognosis in advanced
      gastric cancer.
AB  - BACKGROUND/AIMS: The growth pattern of advanced gastric carcinoma, based on
      volumetric analysis, is closely associated with the biological characteristics of
      tumors, including DNA ploidy, and is an important prognostic factor. Abnormality
      of the p53 tumor suppressor gene plays an important role in alteration of cells
      and possibly leads to cancer development. MATERIALS AND METHODS: Expression of
      tumor suppressor gene p53 was investigated immunohistochemically in the primary
      lesion of 196 patients with advanced gastric cancers, and the relationship of p53
      immunopositivity with the growth pattern and prognosis was analyzed. RESULTS:
      Positive p53 staining was found in 94 (48%) of the 196 primary carcinomas. Vessel
      invasions were more frequent and lymph node metastasis was more extensive in p53
      positive tumors (p < 0.05), whereas p53 immunopositivity was not associated with
      depth of cancer invasion nor with the stage of cancer. In the column and mountain
      type tumors, characterized by vertical or penetrative growth, positive p53
      staining was found in 53.8% and 52.9%, respectively. In the funnel type tumor,
      characterized by superficially spreading growth, positive p53 staining was found
      in significantly lower incidence (28.9%, p < 0.05). The 5-year survival rates
      were 44.2% and 25.4% for patients with p53 negative and positive gastric
      carcinomas, respectively (p < 0.01). Multivariate analysis showed that p53
      overexpression was an independent prognostic factor of patients with advanced
      gastric cancer. CONCLUSIONS: These findings suggest that p53 gene alteration is
      associated with less favorable prognosis of advanced gastric cancer, possibly by
      providing tumors with a potential of vertical growth into the gastric wall.

PMID- 9164534
TI  - Significance of routine annual esophagram for early detection of carcinoma of the
      esophagus.
AB  - BACKGROUND/AIMS: In order to achieve increased survival rates for patients with
      carcinoma of the esophagus, early detection of the disease is vital. Serial
      esophagrams were evaluated to clarify which interval would be effective for early
      detection of carcinoma of the esophagus during routine examination. MATERIALS AND
      METHODS: One hundred eighty-nine patients with carcinoma of the esophagus were
      grouped into three, according to the experience and the time of the previous
      roentgenograms before the definite diagnosis. RESULTS: Five patients were in
      Group 1, in which roentgenographic examination had been done within 12 months
      prior to the diagnosis. Retrospective observation revealed a slight but certain
      abnormal shadow at the same location as the esophageal tumor seen on the second
      films. In Group 2, seven had received an esophagram between 12 and 24 months
      before the diagnosis. In contrast to Group 1, neither abnormality nor findings
      indicating esophageal tumors were detected on the former x-ray films, in all
      seven cases. Group 2 was characterized by relatively small tumors and low stage
      of the disease. Mean tumor length was 4.1 +/- 2.9 cm, and three of seven were
      classified as Stage I and two as Stage IIA. On the other hand, most of the 177
      patients in Group 3, with no previous examination of the esophagus within 24
      months before the diagnosis, had far advanced disease. Mean tumor length was 6.3
      +/- 2.6 cm. Only nine (5.1%) were classified as Stage I, whereas 115 (65.0%) were
      classified as Stage III or IV. CONCLUSION: In light of these data, for
      populations in which esophageal cancer frequently occurs, esophageal examination
      every 12 months will no doubt contribute towards the early detection of lesions.

PMID- 9164536
TI  - Clinicopathological characteristics of stage 1 gastric cancer: comparison of
      macroscopic and microscopic findings.
AB  - BACKGROUND/AIMS: Laparoscopic surgery or endoscopic mucosal resection for early
      stages of gastric cancer have been introduced recently in many regions. In such
      cases, a precise diagnosis is needed prior to treatment, since understaging of
      gastric cancer may lead to treatment failure and impairment of curability and
      prognosis. The clinicopathological features of understaged cases in macroscopic
      Stage 1 gastric cancer have not been clarified yet. MATERIAL AND METHODS: We
      examined 435 patients with intra-operative findings of macroscopic Stage 1
      gastric cancer and compared clinicopathological features of 354 patients (Group
      A) with both macroscopic and histological stage 1 cancer and 81 patients (Group
      B) with macroscopic Stage 1 but histologically proven to be more advanced cancer.
      RESULTS: Among 435 patients with macroscopic Stage 1, there were 81 (18.6%) with
      histologically more advanced stages (44 of stage 2, 34 of stage 3, and 3 of stage
      4). There were no statistical differences in age, sex, operative procedure, and
      extend of lymph node dissection between the groups. Carcinomas in the 81 Group B
      patients tended to have larger tumors (> 4 cm), located in the middle third and
      along the lesser curvature of the stomach, appeared to be Borrmann V type
      (unclassified type) and were histologically more often associated with
      undifferentiated type, INF-gamma, lymphovascular invasion, lymph node metastasis,
      and invasion into a layer deeper than submucosa, all of which resulted in
      significantly poorer prognosis. CONCLUSIONS: Pre-operative and intra-operative
      assessment of the stage for gastric cancer was not always accurate enough and
      about one fifth cases with macroscopic Stage 1 gastric cancer were understaged.
      Thus, we recommend gastrectomy plus radical lymphadenectomy (at least D2) for the
      treatment of choice, from the points of view of curability and prognosis when
      gastric carcinoma is associated with the above mentioned characteristics.

PMID- 9164537
TI  - Pancreatic pseudocyst: the controversial value of total parenteral nutrition.
AB  - BACKGROUND/AIMS: Total parenteral nutrition (TPN) for the non-operative treatment
      of acute pancreatic pseudocyst has been of hypothetical benefit. MATERIALS AND
      METHODS: We reviewed pseudocyst hospital admissions in 40 patients treated with
      TPN who had serial imaging studies. The mean cyst size was 7.4 cm on
      presentation, decreasing to 5.6 cm after non-operative treatment with TPN (mean
      32.5 days). RESULTS: After a non-operative period, 68 percent of pseudocysts
      regressed, completely in 14 percent, partially in 54 percent. Except for a
      patient with cyst-related obstructive jaundice, there were no complicated
      pseudocysts. Only 12 (28%) patients underwent cyst drainage. Fifteen patients
      (35%) sustained catheter-related complication, which included sepsis (26%),
      pneumothorax (9%), hydropneumothorax (2%), and septic right atrial thrombosis
      (2%), in the course of hospitalisation. CONCLUSION: The majority of TPN-related
      patients had a clinical and radiographic regression of their pseudocysts.
      However, the increased risk of catheter-related complications in this group
      suggests that this therapy should be limited to patients who are unable to
      sustain enteral nutrition.

PMID- 9164538
TI  - Duodenum-sparing resection of the pancreatic head combined with
      pancreatogastroanastomosis in the treatment of chronic pancreatitis--surgical
      technique.
AB  - Chronic pancreatitis is defined as progressively developing disease which reduces
      exocrine parenchyma and decreasing exocrine capacity of the pancreas. The disease
      is commonly manifested by recurrent attacks of severe and often incapacitating
      upper abdominal and back pain. The goal of surgical therapy is pain relief and
      unblocking of the stenosis of the common bile duct and duodenum. Our method of
      solving this problem is a duodenum sparing resection of the pancreatic head
      followed by simple reconstruction of the gastrointestinal tract using
      pancreatogastroanastomosis. All unnecessary anastomoses are thus reduced and the
      risk of anastomotic leak is minimized. The substantial advantage of this
      operation is the removal of the pancreatic head where the source of symptoms
      related to chronic pancreatitis is localized.

PMID- 9164539
TI  - Simultaneous hepatic resection with pancreato-duodenectomy for metastatic
      pancreatic head carcinoma: does it improve survival?
AB  - BACKGROUND/AIMS: To determine whether aggressive surgery, consisting of a
      simultaneous pancreatic and partial hepatic resection, for patients with an
      invasive metastatic ductal adenocarcinoma of the pancreatic head improves the
      postoperative outcome. MATERIALS AND METHODS: A total of 109 patients with
      adenocarcinoma of the pancreatic head were divided into two groups. Group 1
      consisted of 33 patients with liver metastasis and Group 2 consisted of 76
      patients without liver metastasis. Group 1 was further subdivided into 11
      patients(Group 1-A) to aggressive surgery, consisting of pancreatoduodenectomy
      and partial liver resection, and 22 patients to palliative bypass surgery(group 1
      B). Group 2 was subdivided into 37 patients to pancreatoduodenectomy(group 2-A),
      and 39 patients to bypass surgery(group 2-B). RESULTS: No significant statistical
      differences were seen in the outcomes between Group 1-A (median survival period:
      6 months) and Group 1-B (median survival period: 4 months). Further, all Group 1
      A patients died from multiple recurrent liver metastasis within a year. In
      addition, the outcomes of Group 1-A were significantly poorer than that of 2-A
      patients(median survival period: 24 months). CONCLUSION: Patients who underwent
      an aggressive simultaneous resection of primary and metastatic hepatic lesion did
      not exhibit any improvement. However, it is anticipated that these findings will
      provide insights into developing an effective adjuvant therapy to impede or
      destroy macroscopic/occult liver metastasis.

PMID- 9164540
TI  - Hepatic osteodystrophy: a review.
AB  - The physiopathology, diagnosis and treatment of hepatic osteodystrophy are
      discussed in this review. Hepatic osteodystrophy (HO) is a generic definition for
      the metabolic bone disease that may occur in individuals with chronic liver
      disease. Two distinct bone metabolic processes, osteoporosis (OP) and
      osteomalacia (OM) are combined together in various proportions in HO syndromes.
      The relative importance of these two diseases in a given case is quite variable.
      HO is a common complication among individuals with long time lasting hepatic
      disease, particularly those with cholestasis. Since advanced HO is difficult to
      treat and adversely affects both the quality of life and the long-term prognosis
      of patients with chronic liver disease, special care is required in order to
      prevent the development of clinical bone disease in individuals with advanced
      hepatic disease.

PMID- 9164541
TI  - Gastric banding in the treatment of morbid obesity.
AB  - BACKGROUND/AIMS: Obesity appears to be an epidemic problem now. Thirty percent of
      men and 40% of women in the fifth decade are obese (> 20% over ideal weight).
      Extreme obesity in itself decreases life expectancy and is associated with the
      early development of cardiopulmonary disorders, hypertension, diabetes and many
      other disorders. The non-operative treatment of extreme obesity rarely leads to
      permanent weight reduction. Various operative procedures such as vertical banded
      gastroplasties, malabsorptive operations or gastric bandings have been suggested
      for the production of permanent weight loss. A relatively high incidence of
      morbidity following "laparotomy" procedures for obesity treatment prompted us to
      start laboratory studies in 1991 on laparoscopic gastric banding. MATERIAL AND
      METHODS: In June 1993 we performed the world's first "laparoscopic" gastric
      banding in a human and since then, we have operated on more than 60 patients
      using this method. RESULTS: The 5-year mean post-operative weight loss of -37.4
      kilograms, with significant blood pressure decreases at 1-year follow-up and with
      no significant changes noted in the levels of RBC, electrolytes and transaminase.
      CONCLUSION: The "laparoscopic" approach in gastric banding enabled us to shorten
      hospital stay and decrease post-operative complications significantly.

PMID- 9164542
TI  - Technical devices in jejunal pouch reconstruction following total gastrectomy,
      including postoperative results.
AB  - BACKGROUND/AIMS: Either straight Roux-en-Y anastomosis or jejunal interposition
      used to be adopted following total gastrectomy. However, dissatisfaction with
      regard to postoperative quality of life has prompted the development of new
      techniques. The purpose of this study is to describe and assess the authors'
      technical devices in jejunal pouch (J-pouch) reconstruction following total
      gastrectomy and the results of these operations. PATIENTS AND METHODS: A
      prospective study of 17 patients with malignant gastric disease (nine with J
      pouch interposition, eight with J-pouch Roux-en-Y reconstruction) was performed.
      To facilitate the side-to-side anastomosis of the jejunal loop, the authors used
      an autosuture instrument. The anastomosis was then checked for hemostasis using a
      vaginoscope. RESULTS: An Endo GIA with a 60-mm long white cartridge (closed
      height of staples, 1.0 mm) is the instrument of choice to create the J-pouch.
      This autosuture instrument fires triple staggered staple lines, which minimizes
      bleeding from the anastomosed site and reduces operative time. No anastomotic
      leaks were associated with the autosuture instrument. The vaginoscope facilitates
      a direct observation of the staple lines internally and if necessary, enables
      secure hemostasis with sutures. Bowel motility was satisfactory for both surgical
      procedures, as measured by the percentage of radiopaque markers which were
      expelled from the pouch. There were no serious complications, and all patients
      have currently survived, a maximum of 5 years and 6 months after surgery, except
      for one patient who died from recurrent disease. CONCLUSION: The authors'
      procedures for J-pouch reconstruction are advantageous due to a favorable
      postoperative quality of life, with low complication rates.

PMID- 9164543
TI  - Helicobacter pylori after surgery for duodenal ulcer.
AB  - BACKGROUND/AIMS: The role of Helicobacter pylori as a cause of peptic ulcer is
      still subject to controversy. The Kock's postulates have not been yet fulfilled;
      the bacteria can be found in normal persons, and it persists in the stomach after
      the ulcer is healed. MATERIAL AND METHODS: The authors analyzed 41 persons
      formerly submitted to surgery (after 8 years and 4 months, as a mean), 31 to
      highly selective vagotomy, and 10 to truncal or selective vagotomy plus
      gastroduodenal drainage. All of them were asymptomatic, or had symptoms not
      related to ulcer relapse. RESULTS: At endoscopy the ulcers were healed in all 41
      individuals, and there was evidence of gastritis in three. The histopathological
      exam showed gastritis in all biopsy specimens. The search of H. pylori by urease
      method and by Giemsa staining was positive in 40. CONCLUSION: It was concluded
      that the gastric acid secretion reduced by vagotomy was the main factor to
      healing the ulcer, not subordinated to H. pylori.

PMID- 9164544
TI  - Relationship of p53 and c-erbB-2 expression to histopathological features,
      Helicobacter pylori infection and prognosis in gastric cancer.
AB  - BACKGROUND/AIMS: Conflicting results concerning the relationships between
      abnormal expression of p53 and c-erbB-2 and biologic behavior of gastric cancer
      are noted. Therefore, overexpression of p53 and c-erbB-2 in relation to the
      following aspects of gastric cancer: tumor histopathology, Helicobacter pylori
      infection, and prognosis are explored. MATERIALS AND METHODS: Expression of p53
      and c-erbB-2 by immunohistochemistry was correlated with histopathology, H.
      pylori infection and prognosis of gastric cancer in 112 patients. RESULTS:
      Positive p53 staining was found in 61 (54.5%) of 112 tumors examined. There was
      no association of p53 expression with sex, age, lymph node metastasis, H. pylori
      infection or prognosis. A significantly higher frequency of p53-positive staining
      was observed in advanced (60.7%), intestinal (69.8%) and cardia (76.5%) than in
      early (30.4%, p < 0.01), diffuse (34.7%, p < 0.01) and noncardia (50.5%, p <
      0.05) carcinoma, respectively. Expression of c-erbB-2 was found in 34 cases
      (30.3%), and was not related to sex, age, H. pylori infection and tumor location.
      Tumors with positive c-erbB-2 staining appeared to behave more aggressively in
      view of higher rates of nodal metastasis (38.0% vs 17.1%, p < 0.05), advanced
      stage (37.1% vs 4.3%, p < 0.01) and poor mean survival (p < 0.01). Patients with
      intestinal type tumors also had a significantly higher rate of c-erbB-2
      expression than those with diffuse tumors (39.7% vs 18.4%, p < 0.01).
      CONCLUSIONS: Our results indicate that immunohistochemical expressions of p53 and
      c-erbB-2 are significantly associated with some histopathological phenotypes.
      Genetic alterations of c-erbB-2 or p53 may not be affected by H. pylori
      infection. C-erbB-2 expression may be used as a marker for identifying more
      aggressive gastric cancer for designing further therapy.

PMID- 9164545
TI  - Multiple leiomyosarcoma of the stomach.
AB  - Leiomyosarcoma is the second most common non epithelial malignant tumor of the
      stomach. It is almost always a single lesion. Multiple leiomyosarcomas of the
      stomach are extremely rare. To our knowledge only three cases have been reported
      so far. We present a 40 year old female with epigastric pain, nausea, diarrhea,
      weight loss and melena in whom we diagnosed multiple lesions of the stomach. At
      operation, we found a total of 11 submucosal or subserosal lesions ranging in
      size from 0.5 to 6 cm in diameter localized throughout the stomach. Histological
      examination showed leiomyosarcoma in every lesion. Almost all the lymph nodes
      along curvatures had metastases. Other lymph nodes, peritoneum, liver and other
      organs were disease free. A total gastrectomy and Roux-en-Y esophagojejunostomy
      was performed. She had an uneventful recovery and has remained symptom-free so
      far (nine months).

PMID- 9164546
TI  - Role of medial preoptic area beta adrenoceptors in the regulation of sleep
      wakefulness.
AB  - The role of the medial preoptic area (mPOA) beta adrenergic receptors in the
      regulation of sleep-wakefulness (S-W) was investigated in this study. S-W was
      assessed on the basis of polygraphic recording of EEG, EMG and EOG in free moving
      rats. Intracerebral microinjection of beta agonist, isoproterenol, into the mPOA
      produced arousal. The study was also conducted on another set of rats in which
      noradrenergic (NE) innervation to the mPOA was destroyed by injecting 6
      hydroxydopamine into the ventral noradrenergic bundle, in the brain stem. Local
      application of isoproterenol, into the mPOA, in these animals, did not produce
      any significant change in S-W. Thus, the increase in awake period obtained on
      isoproterenol administration was the result of its action on the presynaptic NE
      terminals. Possible involvement of other responses in the isoproterenol induced
      increase in wakefulness, is discussed.

PMID- 9164547
TI  - The selective cannabinoid antagonist SR 141716A blocks cannabinoid-induced
      antinociception in rats.
AB  - The purported CB1 cannabinoid antagonist SR 141716A has proven to be a useful
      tool in the investigation of cannabinoid pharmacology. This antagonist was
      employed in the present study to investigate the antinociceptive and cataleptic
      effects of cannabinoids after either systemic or intracerebroventricular (ICV)
      administration. The antinociceptive potency of systemically administered delta 9
      tetrahydrocannabinol (delta 9-THC) was decreased 18-fold by SR 141716A, from an
      ED50 value of 0.3-5.1 mg/kg. Similarly, it completely blocked the antinociceptive
      effects of delta 9-THC and CP 55,940, a potent bicyclic cannabinoid, after ICV
      administration. In addition, it prevented cannabinoid-induced catalepsy when
      given by either route of administration. In contrast, SR 141716A failed to
      antagonize the antinociceptive effects of morphine, indicating its selectivity
      for cannabinoid receptors. These findings indicate that the antinociceptive and
      cataleptic effects of delta 9-THC and CP 55,940 are mediated through CB1
      cannabinoid receptors.

PMID- 9164548
TI  - Locomotor activity and dopamine synthesis following 1 and 15 days of withdrawal
      from repeated apomorphine treatments.
AB  - In two experiments, the effects of repeated apomorphine treatments on locomotor
      activity and terminal field dopamine synthesis was assessed after either a 1- or
      15-day withdrawal period. In the first experiment, rats (n = 11/group) were
      treated with apomorphine (1.0 mg/kg, s.e.) or vehicle and tested for locomotor
      activity daily for 10 days. Fifteen days after the last repeated treatment, all
      rats received 1.0 mg/kg apomorphine and were tested for locomotor activity.
      Locomotor sensitization developed over the 10 day period and was still evident
      after the 15-day withdrawal period. In the second experiment rats (n = 11/group)
      were treated with apomorphine (1.0 mg/kg, s.c.) or vehicle and tested for
      locomotor activity daily for 10 days. Dopamine synthesis was assessed following 1
      or 15 days of withdrawal by measuring dihydroxyphenylalanine (DOPA) accumulation
      (after DOPA decarboxylase inhibition with NSD-1015) in striatum and nucleus
      accumbens-olfactory tuberele. As in the first experiment, rats treated with
      repeated apomorphine showed locomotor sensitization over the 10 days, relative to
      controls. Dopamine synthesis was reliably enhanced in the striatum, but not
      nucleus accumbens-olfactory tuberele, following both 1- and 15-day withdrawal
      periods. These results indicate that enhanced basal dopamine synthesis following
      repeated apomorphine treatments, similar to locomotor sensitization, is a
      persistent phenomenon.

PMID- 9164549
TI  - Increased S(-)-apomorphine-induced vacuous chewing and attenuated effect of
      chronic haloperidol treatment in streptozotocin-induced diabetic rat.
AB  - The incidence of S(-)-apomorphine-induced vacuous chewing movements (VCMs) as a
      model for tardive dyskinesia was investigated in streptozotocin (STZ)-induced
      diabetic rats. A single dose of STZ (65 mg/kg, intravenously) caused a diabetic
      state (hyperglycemia, 480-490 vs. 116-118 mg/dl in naive rats). S(-)-apomorphine
      (250 micrograms/kg, subcutaneously)-induced VCMs were significantly intensified
      in diabetic rats which had received STZ 9 weeks previously. The enhancement of
      VCMs was also observed in nondiabetic rats which received subsequent treatment
      with depot haloperidol (4 mg/kg, intramuscularly, once a week, every week for 4
      weeks) followed by a 2-week washout period. The ability of haloperidol to enhance
      VCMs was attenuated in diabetic rats. The implications of these results in
      relation to altered neurotransmissions in STZ-induced diabetes are discussed.

PMID- 9164551
TI  - Associative and nonassociative tolerance: the effects of dose and interdose
      interval.
AB  - Two experiments examined the effects of dose and interdose interval (IDI) on
      associative and nonassociative tolerance to morphine analgesia in rats.
      Associative contingencies were manipulated by administering low (5 mg/kg) or high
      (20 mg/kg) doses of morphine explicitly paired or unpaired with a distinctive
      context. Nonassociative processes were manipulated by administering morphine at a
      short (6-h) or long (96-h) IDI. Tolerance was assessed as shifts in morphine dose
      response curves on the tail-flick test. Animals in the long IDI conditions showed
      considerable context-specific tolerance. Tolerance in the short IDI conditions
      was not influenced by contextual contingencies at the immediate test (Experiment
      1) and showed no retention over a 30-day interval (Experiment 2), suggesting this
      tolerance was nonassociative. The impact of massed exposure to morphine and
      context on the disruption of learning at the short IDI is discussed.

PMID- 9164550
TI  - Dissociation of hypnotic-anesthetic actions of alpha 2 agonists from cyclic AMP
      in the rat.
AB  - alpha 2 adrenergic agonists are used clinically for their anesthetic, analgesic,
      and sympatholytic actions in surgical patients. All alpha 2 adrenergic receptors,
      when activated by alpha 2-adrenergic agonists, are able to inhibit adenylate
      cyclase. We have examined the alpha 2-adrenoceptor-mediated anesthetic actions of
      dexmedetomidine, a highly selective alpha 2-adrenergic agonist, after
      pretreatment of the animals with rolipram, a cyclic AMP (cAMP)-specific
      phosphodiesterase inhibitor, cAMP accumulation and monoamine turnover were
      measured in the locus coeruleus (LC) and hippocampus (HC) following
      administration of rolipram [275 mg/kg, intraperitoneally (IP)] and
      dexmedetomidine (100-500 mg/kg, IP). The hypnotic response to dexmedetomidine was
      also measured in these animals. In other experiments, rats were stereotactically
      cannulated in the LC with an indwelling catheter, and after the second day, the
      tail-flick analgesic response to dexmedetomidine (3.5 mg/0.2 ml LC), following
      rolipram (275 mg/kg, IP) pretreatment, was assessed. In the presence of elevated
      cAMP levels, the hypnotic, analgesic, and sympatholytic effects of
      dexmedetomidine persisted. These data suggest that adenylate cyclase activity
      does not mediate the cellular responses to alpha 2-adrenergic agonists but
      instead may act in concert with other alpha 2-adrenoceptor-coupled effector
      mechanisms to transduce the anesthetic actions of these agents.

PMID- 9164552
TI  - The effects of central and peripheral angiotensin on hypertension and nociception
      in rats.
AB  - Spontaneously hypertensive rats (SHRs) rats have been reported to have decreased
      sensitivity to pain, but as yet a mechanism has not been identified. This study
      investigated the effects of subcutaneous and intracerebroventricular (ICV)
      infusions of angiotensin II on blood pressure, locomotor activity, and tailflick
      and hot plate latencies in the Wistar-Kyoto (WKY) and outbred Wistar rat.
      Peripheral but not central administration of angiotensin II (567
      micrograms/kg/day) increased hot plate latencies in WKY and Wistar rats to a
      level equivalent to that observed in the SHR. Peripheral administration of
      norepinephrine (50 and 100 mg/kg/day) to WKYs increased blood pressure but had no
      effect on hotplate latency. ICV administration of losartan (1 & 3 mg/kg/day) to
      SHRs had no effect on blood pressure or nociception. The results indicate that
      angiotensin II has a role in the altered pain perception observed in the SHR and
      that its site of action is peripheral.

PMID- 9164553
TI  - Tolerance and sensitization to the behavioral effects of cocaine in rats:
      relationship to benzodiazepine receptors.
AB  - Tolerance and sensitization to the behavioral effects of cocaine were
      investigated in rats responding under a fixed-consecutive-number eight schedule
      of food reinforcement. The development of tolerance or sensitization was induced
      by delivering the drug either immediately before or after each behavioral session
      during chronic administration. Chronic cocaine administered before each session
      resulted in tolerance, as indicated by the shift to the right in the cocaine dose
      response curve. This tolerance was more likely to develop in the presence of an
      external discriminative stimulus. On the other hand, when cocaine was delivered
      after each session, the injections did not disrupt responding and sensitization
      or increased sensitivity rather than tolerance developed. This sensitization was
      more likely to occur when the external discriminative stimulus was not present.
      These data suggest that either tolerance or sensitization to the behavioral
      effects of cocaine can occur following the same number of chronic injections,
      with the effect dependent on the context under which the drug is delivered.
      Significant differences in benzodiazepine receptor binding measured
      autoradiographically using [3H]flumazenil were observed between rats that
      received cocaine before or after each session, suggesting that the development of
      tolerance and sensitization may be mediated through changes in benzodiazepine
      receptors in discrete brain regions.

PMID- 9164554
TI  - Effects of mu- and delta-opioid-receptor antagonists on the stimulus properties
      of cholecystokinin.
AB  - Melton and Riley recently reported that the relatively selective mu-opioid
      antagonist naloxone potentiated the stimulus properties of the gut peptide
      cholecystokinin (CCK). To assess whether such opioid potentiation is limited to
      activity at the mu-receptor subtype, in the present experiment the effects of the
      highly selective delta-antagonist naltrindole on CCK's stimulus properties were
      examined. Because in the initial report of naloxone's potentiation of CCK a
      relatively high, nonphysiologic dose of CCK (i.e., 13 micrograms/kg) was used as
      the training drug, in the current analysis subjects were trained to discriminate
      5.6 micrograms/kg CCK from its vehicle and the assessments and comparisons of the
      effects of naloxone and naltrindole were based on this dose. Specifically, rats
      were administered 5.6 micrograms/kg CCK before saccharin-LiCl pairings and the
      CCK vehicle before saccharin alone. With such training, they rapidly acquired the
      drug discrimination, avoiding saccharin consumption when it was preceded by CCK
      and consuming the same saccharin solution when it was preceded by its vehicle. In
      subsequent generalization tests, doses of CCK that were ineffective in
      suppressing saccharin consumption (i.e., did not substitute for the training dose
      of CCK) did result in the suppression of saccharin consumption when combined with
      doses of the mu antagonist naloxone that alone had no effect on saccharin intake.
      On the other hand, the highly selective delta-opioid-receptor antagonist
      naltrindole was ineffective in potentiating the effects of CCK. Specifically,
      when naltrindole was combined with ineffective doses of CCK, subjects drank at
      control levels. The ability of naloxone to potentiate CCK's stimulus effects is
      consistent with a range of other demonstrations of the role of the mu-opioid
      receptor subtype in CCK-opioid interactions, although the specific basis for the
      interaction remains unknown. Given recent findings on the effects of delta
      agonists and antagonists on CCK-induced activity, the failure of naltrindole to
      potentiate CCK's stimulus effects may be due to the absence of delta activity
      within this preparation, rather than the absence of delta mediation of CCK-opioid
      interactions in general.

PMID- 9164555
TI  - Chronic treatment with dexmedetomidine desensitizes alpha 2-adrenergic signal
      transduction.
AB  - Tolerance to the hypnotic response was induced in rats by chronically infusing
      dexmedetomidine, a novel alpha 2-adrenergic agonist. The alpha 2-adrenoceptor
      affinity for dexmedtomidine and para-iodoclonidine was significantly reduced in
      tolerant rats, while Bmax was uncharged. The ability of pertussis toxin (PTX) to
      ribosylate guanine nucleotide regulatory proteins (G proteins) ex vivo was
      reduced in tolerant rats; the quantity of PTX-sensitive G proteins was unchanged.
      Forskolin-stimulated adenylyl cyclase was less sensitive to inhibition by
      dexmedetomidine in the tolerant rats; however, acute intraperitoneal injection of
      dexmedetomidine still reduced cyclic adenosine monophosphate levels in tolerant
      rats. Both the decrease in ribosylation and the lower alpha 2-adrenoceptor
      binding affinity may reflect a decrease in the ability of the G protein to couple
      to the alpha 2-adrenoceptors in the locus coeruleus of tolerant rats. In this
      state, the alpha 2 adrenoceptors are less capable of transducing the effector
      response (inhibition of adenylyl cyclase).

PMID- 9164556
TI  - The interaction of dopamine, cocaine, and cocaethylene with ethanol on central
      nervous system depression in mice.
AB  - The interactions between dopamine, cocaine, cocaethylene, and ethanol were
      studied in Swiss-Webster mice. The loss of the righting reflex (LORR) was used as
      a measure of CNS depression. Animals were injected intraperitoneally (IP) with
      ethanol (4.0 g/kg). which caused a LORR. Immediately upon regaining of the
      righting reflex, mice were injected intracerebroventricularly (ICV) with saline,
      dopamine (0.1, 0.5, or 1.0 mumol/kg), cocaine (1, 15, or 25 mumol/kg), or
      cocaethylene (1, 15, or 25 mumol/kg). In the presence of systemic ethanol, all
      three compounds produced CNS depression in a dose-dependent manner. The dopamine
      D2-receptor antagonist sulpiride and the D1-receptor antagonist fluphenazine were
      given acutely ICV with dopamine in the presence of systemic ethanol to examine
      whether these antagonists could block the return to the LORR produced by
      dopamine. Sulpiride, however, actually enhanced the interaction between ethanol
      and dopamine in a dose-dependent manner as measured by the LORR; fluphenazine
      neither blocked nor enhanced the effect of dopamine in the presence of systemic
      ethanol. In addition, these antagonists had no effect on cocaine- and
      cocaethylene-induced CNS depression in the presence of systemic ethanol. The
      results of this study showed that the neurotransmitter dopamine and both cocaine
      and cocaethylene can promote further CNS depression in the presence of systemic
      ethanol, and that dopamine was significantly more potent than cocaine and
      cocaethylene as measured by the return to the LORR.

PMID- 9164557
TI  - Effects of d-amphetamine on temporal distributions of schedule-induced
      polydipsia.
AB  - Food-deprived rats were divided into four groups according to the equal interval
      and time durations of a multiple fixed-interval, fixed-time schedule (15, 30, 60,
      and 120 s). Fixed-time components were signaled by a tone and lever withdrawal. d
      Amphetamine (0.25-4.0 mg/kg) produced similar dose-dependent reductions in the
      drinking and licking induced by fixed-interval and fixed-time schedules. These
      dose-dependent decrements were a function of the interfood interval length. More
      licks occurred early in the interfood intervals with doses of d-amphetamine. Dose
      dependent shifts to the left were observed in the distribution of licking, and
      there were dose-dependent decreases in the quarter-life, which were a function of
      fixed-interval and fixed-time lengths. The maximum lick rate within interfood
      intervals occurred at about the same absolute time in schedules up to 60 s;
      therefore, the effects of d-amphetamine were not mediated by its effects on
      temporal discrimination.

PMID- 9164558
TI  - Persistent increases in basal cerebral metabolic activity induced by morphine
      sensitization.
AB  - To characterize the underlying neuroanatomic substrate of morphine (MS)
      sensitization, changes in the local cerebral metabolic rate for glucose (LCMRglu)
      were examined in 95 brain regions of male F-344 rats using the 2-deoxy-D-[1
      14C]glucose method. The results of these experiments demonstrate that MS-induced
      sensitization is manifested by increases in basal metabolic activity that last
      for at least 6 days. Although changes in basal metabolic rate were found to be
      more extensive in the presence of conditioned cues, the increases in LCMRglu in
      nonconditioned sensitized rats indicate a basic underlying pharmacologic effect
      of MS sensitization on basal brain activity. Regions in which MS sensitization
      had a lasting pharmacologic effect include the shell of the nucleus accumbens,
      the prelimbic area of the prefrontal cortex, and the dorsolateral prefrontal
      cortex. Interestingly, the core of the nucleus accumbens and regions of the
      caudate were found to have an increased LCMRglu only in the presence of
      conditioned cues, indicating conditioned brain activity without observable
      changes in behavior. The previous administration of an MS-sensitizing treatment
      was also found to alter the cerebral metabolic response to a subsequent acute MS
      challenge (0.5 mg/kg, subcutaneously), most notably in forebrain systems. The
      more widespread activation of brain structures in the basal state in the presence
      of conditioned cues suggests that these MS-sensitized rats may model an altered
      brain state related to craving in the abstinent opiate addict.

PMID- 9164559
TI  - Effect of lipid solubility on the development of chronic cross-tolerance between
      ethanol and different alcohols and barbiturates.
AB  - Tolerance to ethanol and cross-tolerance to other alcohols (n-propanol, n
      butanol, t-butanol, isobutanol, t-amyl alcohol, n-amyl alcohol, and benzyl
      alcohol) and barbiturates (pentobarbital, secobarbital, amobarbital, thiopental,
      barbital and phenobarbital) that differ in lipid:water partition coefficient was
      examined in rats after chronic pretreatment with ethanol. Tolerance and cross
      tolerance were studied with three different measures (hypothermia, tilt-plane,
      and rotarod). Tolerance to ethanol resulted in significant cross-tolerance to
      alcohols with low lipid solubility (n-propanol and t-butanol), whereas no cross
      tolerance was seen with alcohols of high lipid solubility (isobutanol, n-amyl
      alcohol, t-amyl alcohol and benzyl alcohol). Cross-tolerance to n-butanol (which
      has intermediate lipid solubility) appeared to be metabolic rather than
      functional. Tolerance to ethanol also resulted in significant cross-tolerance to
      barbital and phenobarbital, but not to pentobarbital, secobarbital, amobarbital
      or thiopental. These studies suggest that lipid solubility is an important factor
      in relation to specificity of cross-tolerance to alcohols and barbiturates.

PMID- 9164560
TI  - The effects of pentobarbital on spatial learning, motor coordination, and
      exploration.
AB  - Mice injected with either 8, 16 or 32 mg/kg of pentobarbital were as efficient as
      control subjects in learning and recalling the location of a submerged platform
      in a water maze. The highest dose of pentobarbital decreased fall latencies in
      the coat-hanger test of motor coordination. Exploratory activity was not affected
      by these doses of pentobarbital. The absence of a deficit in spatial learning and
      in exploratory activity occurred even at a dose sufficient to cause a deficit in
      motor coordination. These results stand in contrast to previous findings
      indicating spatial deficits in rats injected with benzodiazepines.

PMID- 9164561
TI  - Cocaine--stimulus generalization to MDA optical isomers: a reevaluation.
AB  - It has already been demonstrated that the psychoactive agent 1-(3,4
      methylenedioxyphenyl)-2-aminopropane (MDA) produces effects that are both
      hallucinogen-like and amphetamine or stimulant-like in animals. Hallucinogenic
      activity is associated primarily with the R(-)-isomer of MDA whereas stimulant
      activity is primarily associated with the S(+)-isomer. Because a previous report
      indicates that S(+)MDA fails to substitute for cocaine in rats trained to
      discriminate cocaine from vehicle, and because these findings are inconsistent
      with the purported stimulant nature of S(+)MDA, we reinvestigated the effect of
      both MDA isomers in rats. In this investigation, S(+)MDA doses of 1.25 and 1.5
      mg/kg were found to produce > 80% cocaine-appropriate responding in rats trained
      to discriminate 8 mg/kg of cocaine from saline. However, consistent with a
      previous report, R(-)MDA resulted only in partial generalization. These new
      results support the hypothesis that the optical isomers of MDA produce
      distinguishable stimulus effects in rats and that S(+)MDA is the more stimulant
      isomer of MDA.

PMID- 9164562
TI  - Behavioural effects in mice of subchronic chlordiazepoxide, maprotiline, and
      fluvoxamine. I. Social interactions.
AB  - The present study compares the effects of subchronic administration (daily. 21
      days) of chlordiazepoxide (CD), maprotiline and fluvoxamine on the behavior of
      male mice during dyadic social interactions. Maprotiline like chlordiazepoxide,
      stimulated aggression at 4 mg/kg and 2 mg/kg respectively (intermediate dose
      levels), whereas effects of fluvoxamine (3-8 mg/kg) were mainly sedative. Non
      social activity was reduced by CD at 4 and 8 mg/kg and by maprotiline at 0.5
      mg/kg. At the highest dose tested (10 mg/kg), maprotiline increased immobility,
      resembling the effects of fluvoxamine, while at 2 mg/kg, it reduced social
      investigation. Thus, despite some commonalities, there were several differences
      in behavioral profile of the compounds tested. Data are discussed in relation to
      the efficacy of each of these compounds in treating anxiety and depressive
      disorders.

PMID- 9164563
TI  - Behavioural effects in mice of subchronic chlordiazepoxide, maprotiline and
      fluvoxamine. II. The elevated plus-maze.
AB  - In view of apparent commonalities in the aetiology, symptomatology, and
      pharmacotherapy of anxiety and depressive disorders, the present study compares
      the effects of the benzodiazepine, chlordiazepoxide (1.0-8.0 mg/kg), the
      selective noradrenaline (NA) reuptake inhibitor, maprotiline (0.5-10.0 mg/kg),
      and the serotonin (5-HT)-selective reuptake inhibitor, fluvoxamine (2.0-8.0
      mg/kg), on the behaviour of mice in the elevated plus-maze test of anxiety. To
      more accurately reflect the clinical situation, subjects were treated daily for
      21 days prior to testing, and comprehensive behavioural profiles were obtained
      through the application of an ethological scoring technique. Results show that
      subchronic treatment with chlordiazepoxide produced clear anxiolytic-like effects
      at the highest dose tested, coupled with an inhibition of risk assessment over
      the entire dose range. With the exception of risk assessment measures, anxiolytic
      like effects were also seen with a low dose (0.5 mg/kg) of maprotiline: these
      effects were lost at higher doses. In contrast to these data, fluvoxamine
      produced minimal behavioural change under present test conditions. Findings are
      discussed in relation to the relative efficacy of selective monoamine. reuptake
      inhibitors in the treatment of anxiety disorders, and the nature of anxiety
      evoked in mice by exposure to the elevated plus-maze.

PMID- 9164564
TI  - Central alpha-adrenergic agonists and need-induced 3% NaCl and water intake.
AB  - In the present study, noradrenaline (NOR, alpha-non-specific adrenergic agonist),
      clonidine (CLO, alpha 2), phenylephrine (PHE, alpha 1) or isoproterenol (ISO,
      beta-agonist) was injected in the medial septal area (MSA) of water-deprived,
      sodium-deplete or food-deprived rats. NOR (80, 160 nmol) inhibited the intake of
      3% NaCl, water deprivation-induced and meal-associated water intake. Food
      deprivation-induced food intake and 10% sucrose intake were not altered by NOR.
      CLO (10, 20, 30, 40 nmol) inhibited (80-100% inhibition compared to control
      during 60 min) the intake of 3% NaCl, water deprivation-induced and meal
      associated water intake. CLO had a weaker inhibition on food and 10% sucrose
      intake (30-50% less than the control during 60 and 15 min, respectively). PHE
      (160 nmol) inhibited 3% NaCl intake and 10% sucrose intake (30% less than the
      control for 15-30 min). ISO (160 nmol) did not alter water or 3% NaCl intake. NOR
      induced an increase, CLO and ISO induced a decrease, and PHE no alteration in
      mean arterial pressure. NOR did not alter water or 3% NaCl intake when injected
      unilaterally into the caudate nucleus. The results suggest that NOR injected in
      the MSA acts on alpha 2-adrenergic receptors inducing a specific inhibition of 3%
      NaCl and water intake.

PMID- 9164565
TI  - Concurrent positive and negative goalbox events produce runway behaviors
      comparable to those of cocaine-reinforced rats.
AB  - Rats traversing a straight-alley for reinforcing stimuli typically exhibit faster
      running times as training proceeds. In previous work from this laboratory,
      animals running for a reinforcement consisting of intravenous infusions of
      cocaine, unexpectedly demonstrated a progressive increased time to enter the
      goalbox over trials. Closer observation revealed that the animals were exhibiting
      a unique retreat behavior (i.e., stopping their forward advance toward the
      goalbox and returning toward the startbox). It was hypothesized that the retreat
      behavior reflected an inherent conflict that originated from concurrent positive
      and negative associations with the goalbox. Such associations were attributed to
      cocaine's dual and well documented reinforcing and anxiogenic effects. To test
      this idea, the present study compared the runway behavior of animals that
      concurrently received food and mild foot shock in the goalbox to the behavior of
      the other animals running for cocaine. Results demonstrated that food + shock
      reinforced animals took longer to enter the goalbox and made more retreats than a
      control group that received only food in the goalbox. Both these effects were
      reversed by pretreatment with the anticonflict, anxiolytic drug, diazepam. The
      behavior pattern of animals that received the combination of food and footshock
      was found to strongly resemble that of IV cocaine-reinforced rats, a result
      consistent with the notion that chronic cocaine administration has both positive
      and negative consequences.

PMID- 9164566
TI  - Initial characterization of PMMA as a discriminative stimulus.
AB  - The phenylisopropylamine PMMA or N-methyl-1-(4-methoxyphenyl)-2-aminopropane, a
      structural hybrid of paramethoxyamphetamine (PMA) and methamphetamine, has been
      previously shown to unexpectedly lack amphetamine-like or hallucinogen-like
      stimulus properties in animals. For example, in tests of stimulus generalization,
      neither a (+)amphetamine stimulus nor a DOM stimulus generalized to PMMA. It has
      also been shown, however, that stimulus generalization does occur in animals
      trained to discriminate the designer drug MDMA ("Ecstasy" or N-methyl-1-(3,4
      methylenedioxyphenyl)-2-aminopropane) from vehicle. In order to further
      characterize this unique agent, we trained a group of six Sprague-Dawley rats to
      discriminate 1.25 mg/kg of PMMA (ED50 = 0.44 mg/kg) from saline vehicle. The PMMA
      stimulus failed to generalize to the phenylisopropylamine stimulant
      (+)amphetamine, or to the phenylisopropylamine hallucinogen DOM. Stimulus
      generalization occurred to (+/-)MDMA (ED50 = 1.32 mg/kg) and S(+)MDMA (ED50 =
      0.48 mg/kg). Partial generalization occurred with R(+)MDMA, PMA, 3.4-DMA, and
      fenfluramine. The PMMA stimulus also generalized to the alpha-ethyl homolog of
      PMMA (EH/PMMA, ED50 = 1.29 mg/kg). Taken together, the results of these studies
      suggest that PMMA is an MDMA-like agent that lacks the amphetamine-like stimulant
      character of MDMA. These findings support our previous suggestion that PMMA be
      considered the structural parent of the MDMA-like family of designer drugs.

PMID- 9164567
TI  - Nicotine-containing versus de-nicotinized cigarettes: effects on craving and
      withdrawal.
AB  - Nicotine exposure levels and subjective effects from smoking a de-nicotinized
      cigarette (Next) were examined under controlled conditions. Ten tobacco smokers
      smoked 20 puffs from their own brand (1.1 mg nicotine delivery, commercial
      cigarettes), a 0.7 mg nicotine "light" cigarette, or the Next de-nicotinized
      cigarette (< 0.1 mg nicotine) during independent experimental test sessions. The
      Next cigarette did not deliver and appreciable nicotine, did not elevate heart
      rate during smoking, and was rated as less satisfying than the smokers' own
      brand. Subjective ratings of cigarette carving and tobacco withdrawal symptoms
      increased during a 90 min post-smoking abstinence period. However, there were no
      measurable differences on these subjective ratings across the three cigarette
      test brands. It is concluded that nicotine can be removed from cigarettes without
      affecting the onset time course or intensity of cigarette cravings and other
      tobacco withdrawal symptoms in an acute abstinence model. Further studies to
      determine the subjective and physiological effects of nicotine-free cigarettes
      would contribute to a greater understanding of tobacco withdrawal and the
      processes involved in smoking maintenance.

PMID- 9164568
TI  - Behavioral effects of N-cyanomethylmethamphetamine, a product derived from
      smoking methamphetamine with tobacco, in mice and rats.
AB  - The stimulant effects of N-cyanomethylmethamphetamine (CMMA), a product derived
      from smoking methamphetamine (MA) mixed in tobacco, were studied by observing
      stereotyped behavior and measuring spontaneous motor activity in mice and rats
      over 180 min CMMA. 1.3 and 10 mg/kg IP, elicited strong stimulant-like effects
      which were almost equivalent to those produced by MA. Drug monitoring for 180 min
      in mouse and rat plasma revealed that the principal substances responsible for
      the stimulant effect of CMMA were MA and amphetamine (AP) which were metabolized
      from CMMA by the animal. There was a species difference in metabolism of CMMA
      between mice and rats. The major metabolites were MA and AP in mouse plasma,
      followed by N-formylmethamphetamine (FMA), whereas the major metabolite was FMA
      in rat plasma, followed by MA and AP. The differences in the stimulant effects of
      CMMA between mice and rats were discussed in relation to its metabolic fate in
      mice and rats.

PMID- 9164569
TI  - MDMA and d-amphetamine produce comparable effects in pigeons performing under a
      multiple fixed-ratio interresponse-time-greater-than-t schedule of food delivery.
AB  - The purpose of this study was to gain further information about the behavioral
      effects of (+/-) 3.4-methylenedioxymethamphetamine (MDMA) on schedule-controlled
      responding. MDMA (0.32, 0.56, 1.0, 3.2, 5.6, and 10 mg/kg) and d-amphetamine
      (0.32, 0.56, 1.0, 3.2, 5.6, and 10 mg/kg) were administered to pigeons performing
      under a multiple fixed-ratio 30 (FR 30) interresponse-time-greater-than-15-s (IRT
      > 15-s) schedule of food delivery. In general, both drugs had no significant
      effect on response rates under the IRT > 15-s component at doses that decreased
      rates under the FR component. Results of the present experiment indicate that
      under some conditions MDMA and d-amphetamine produce similar, and rate-dependent,
      effects.

PMID- 9164570
TI  - Exacerbation of ethanol withdrawal seizures in mice with a history of multiple
      withdrawal experience.
AB  - Repeated ethanol withdrawal experience has been shown to result in an
      exacerbation of future withdrawal episodes. This sensitization of the withdrawal
      response has been hypothesized to represent a "kindling" phenomenon. We
      previously demonstrated that mice exposed to ethanol vapor for a total of 48 h
      exhibited more severe withdrawal seizures if the exposure was divided into three
      16 h intoxication/8 h abstinence cycles than if the 48 h of exposure occurred in
      a single bout. The present study was designed to further characterize this model
      of ethanol withdrawal "kindling" and determine whether such a "kindled" response
      may be evident when withdrawal testing is conducted after an additional bout of
      intoxication that is the same for all groups. Adult C3H mice were chronically
      exposed to ethanol vapor in inhalation chambers for 40 h prior to withdrawal
      testing. Prior to this 40 h intoxication period, one group (Multiple Withdrawal;
      MW) received three cycles of 16 h ethanol vapor separated by 8 h abstinence; a
      second group (Single Withdrawal; SW) did not receive any ethanol exposure prior
      to the 40 h test cycle; a third group (Continuous Exposure; CE) received the same
      total ethanol exposure as the MW group (48 hr), but without interruption: and a
      control group (C) did not receive any ethanol treatment throughout the
      experiment. Blood ethanol levels following the 40 h bout of ethanol intoxication
      were 100-140 mg/dl for all ethanol-exposed groups. The severity of handling
      induced convulsions during withdrawal was significantly greater in the MW group
      compared to CE and SW groups. These results suggest that differences in the
      severity of ethanol withdrawal seizures due to differences in prior withdrawal
      experience can be demonstrated even when later ethanol exposure patterns are
      equated. As such, the results provide further support for the "kindling"
      hypothesis of ethanol withdrawal.

PMID- 9164571
TI  - Effects of alpha 1-adrenoceptor and Ca2+ channel inhibition on norepinephrine
      induced thermoregulatory behavior in the cold.
AB  - This experiment examined whether paradoxical temperature-dependent effects of
      norepinephrine (NE) can be blocked by the alpha 1-adrenoceptor antagonist WB 4101
      (WB) and the Ca(2+)-channel blocker nifedipine. An operant lever-pressing task
      was used to measure the demand for heat in a cold environment. As noted
      previously, NE alone (250 micrograms/kg) produced a substantial and significant
      increase in the demand for heat, and yet post-test colonic temperature (Tc) fell.
      When tested alone, WB and nifedipine also increased the demand for heat, but this
      was sufficient to maintain Tc. When combined with NE, WB and nifedipine reduced
      the demand for heat and the fall in Tc such that there were no differences
      between the effects of the blockers given alone or with NE. These results
      indicate that paradoxical thermoregulatory effects of NE in the cold can be
      antagonized effectively by either an alpha 1-adrenoceptor antagonist or a Ca(2+)
      channel blocker.

PMID- 9164572
TI  - Desflurane, enflurane, isoflurane and ether produce ethanol-like discriminative
      stimulus effects in mice.
AB  - In the present studies, drug discrimination procedures were used to compare the
      discriminative stimulus effects of ethanol (ETOH) and several volatile
      anesthetics. Male albino mice were trained to discriminate between IP injections
      of ETOH (1.25 g/kg) and saline in a two-lever operant task in which responding
      was under the control of a fixed-ratio 20 (FR20) schedule of food presentation.
      Stimulus generalization was examined after 20-min inhalation exposures to
      desflurane (4,000-32,000 ppm), enflurane (3,000-12,000 ppm), isoflurane (1,000
      8,000 ppm) and ether (4,000-32,000 ppm). Concentration-related increases in ETOH
      lever responding were observed for all four volatile anesthetics. For enflurane
      and ether, maximal levels of > 85% ETOH-lever responding were obtained at one or
      more concentrations. For desflurane and isoflurane, the maximal mean percentages
      of ETOH-lever responding were somewhat lower, but 6 out of 7 mice showed full
      substitution with desflurane and 5 out of 7 for isoflurane. The shared
      discriminative properties of these compounds with ETOH suggest that these
      anesthetics may share some of ETOH's pharmacological properties. These results
      are similar to previous research results showing ETOH-like discriminative
      stimulus effects in mice with other anesthetics and abused volatile inhalants
      (i.e. halothane, toluene and 1.1,1-trichloroethane) and may reflect the CNS
      depressant drug-like effects of inhaled anesthetics and abused solvents.

PMID- 9164573
TI  - Cross-generalization of an EtOH "hangover" cue to endogenously and exogenously
      induced stimuli.
AB  - Twenty male Sprague-Dawley rats were trained in a two-choice food-reinforced drug
      discrimination task (10 min sessions) using the state-dependent interoceptive
      stimulus attributes of ethanol's (EtOH) delayed or rebound effects (EDE) versus
      "normal" basal homeostasis. Cross-generalization tests were conducted with 0.18
      mg/kg naloxone injected after three days of three injections per day of either
      SAL or 10 mg/kg morphine. Naloxone failed to generalize to the EDE-state after
      chronic saline; however, the precipitated morphine withdrawal state produced
      complete generalization to the EDE training cue. Daily tests were conducted after
      8 h photoperiod phase-shifts. An 8 h phase-advance, equivalent to a west-to-east
      intercontinental night-time flight in humans, produced a biphasic, graded,
      increase in EDE-appropriate responding, which peaked on the second day after the
      phase-advance and recovered by the fourth day. The 8 h phase-delays failed to
      engender significant EDE-appropriate responding. These data provide evidence for
      the subjective similarity between EtOH hangover, opiate withdrawal states, and
      the physiological disruption induced by circadian phase-advances.

PMID- 9164574
TI  - The effect of acute, chronic and chronic intermittent stress on the central
      noradrenergic system.
AB  - The objective of this investigation was to examine the immediate and long term
      effects of acute, chronic and chronic intermittent stress on the central
      noradrenergic system of rats. Male Sprague-Dawley rats were subjected to one hour
      of physical immobilization stress either as a single exposure, or as 14 exposures
      applied either on consecutive days, or randomly over 60 days. Animals were
      sacrificed immediately, 6 h and 24 h following the last stressor. Levels of
      norepinephrine (NE) and 3-methoxy-4-hydroxyphenylethylene-glycol sulfate (MHPG
      sulfate) were measured in the hypothalamus, hippocampus, cerebral cortex and
      locus coeruleus region and beta-adrenergic receptor (BAR) density was determined
      in the cortex. Immediately after acute stress, a significant reduction in
      hypothalamic NE levels and marked increases in MHPG-sulfate levels in all four
      brain regions were observed. In contrast immediately after the last stressor of a
      chronic or chronic intermittent stress regimen, no change in NE concentration was
      observed while levels of MHPG-sulfate in the four brain regions showed a smaller
      increase than that observed after an acute stressor. Acute stress induced changes
      normalized within 6 h while chronic and chronic intermittently stressed animals
      had altered NE or MHPG-sulfate levels in certain brain regions for up to 6-24 h.
      Cortical BAR binding parameters remained unchanged after all stress paradigms.

PMID- 9164575
TI  - Tamoxifen prevents sulpiride-induced weight gain in female rats.
AB  - To evaluate its potential utility in counteracting neuroleptic-induced obesity,
      the effects of long-term administration of tamoxifen (TAM) on body weight (BW)
      and food intake (FI) of gonadally intact and sulpiride-treated (SUL) female rats
      were assessed. In addition, estradiol and prolactin serum levels were measured in
      rats treated with SUL. SUL plus TAM and SUL plus bromocriptine (BR). TAM, at
      doses of 10, 50 and 100 micrograms, significantly decreased BW gain: FI was
      significantly reduced at the doses of 50 and 100 micrograms. In addition, doses
      of TAM ranging from 5-100 micrograms completely prevented SUL-induced BW gain and
      hyperphagia. BR also prevented SUL effects on BW and FI. In contrast to BR,
      concomitant administration of TAM did not prevent SUL-induced hyperprolactinemia.
      Estradiol levels were not modified by SUL alone or SUL plus BR, but they were
      significantly increased in the animals treated with TAM plus SUL. Neuroleptic
      induced obesity in female rats might be related to an alteration in gonadal
      steroid balance secondary to hyperprolactinemia. While BR might counteract
      neuroleptic-induced weight gain by preventing hyperprolactinemia, TAM might
      directly interact with estrogen receptors, or indirectly increase estradiol
      levels. The use of TAM in preventing neuroleptic-induced obesity in humans
      warrants further investigation.

PMID- 9164576
TI  - d-fenfluramine anorexia: dissociation of ingestion rate, meal duration, and meal
      size effects.
AB  - In the present study, we ask whether the suppressive effect of d-fenfluramine (d
      FEN) on short-term intake can be better explained in terms of a primary action on
      particular behavioral parameters (e.g., ingestion rate or meal duration), as
      proposed by several investigators, or in terms of a primary effect on an intake
      "target" that can be achieved via diverse behavioral strategies. We applied two
      specialized intake testing paradigms that constrain the behavioral structure of
      the rat's meal in different ways, and determined whether or not the meal-size
      result varied in turn. (1) In the intraoral intake test, the rate of ingestion
      was clamped by the rate (1.0 ml/min) at which the test stimulus (12.5% glucose)
      was intraorally delivered. A d-FEN (3 mg/kg) suppression of intraoral intake was
      obtained demonstrating that ingestion rate adjustment is not necessary for the
      anorexic effect. In addition, for both d-FEN and vehicle conditions, comparable
      amounts were consumed when the intraoral intake test was either continuous or
      interrupted for 10 min beginning 6 min after test onset. For d-FEN, the increase
      in meal duration (mean = 11.98 min) required to compensate for the imposed
      interruption indicates that the drug does not specify an absolute limit for meal
      duration. (2) In the drop size-controlled spout-licking test, the volume of 12.5%
      glucose delivered for each lick was fixed at either 8 or 4 microliters. There was
      an overall reduction in intake with d-FEN (0.75 mg/kg), but as under vehicle
      injection conditions, the number of licks emitted approximately doubled when lick
      volume was halved. As a result, meal size was unaffected by the drop size
      manipulation. The drop size manipulation affected several other behavioral
      parameters under respective d-FEN and vehicle injection conditions, including:
      average rate of ingestion (ml/min), initial ingestion rate, and ingestion
      duration (meal duration minus pause time). The two experiments together
      demonstrate that the anorexic effect of d-FEN does not depend on adjustment of
      any particular behavioral parameter. The results suggest, rather, that given
      doses of d-FEN establish a particular degree of intake suppression that the rat
      defends via diverse behavioral strategies.

PMID- 9164577
TI  - Functional characterization of the novel neuronal nicotinic acetylcholine
      receptor ligand GTS-21 in vitro and in vivo.
AB  - (2.4)-Dimethoxybenzylidene anabaseine dihydrochloride (GTS-21), a compound that
      interacts with rat neuronal nicotinic acetylcholine receptors (nAChRs), was
      evaluated using human recombinant nAChRs in vitro and various pharmacokinetic and
      behavioral models in rodents, dogs and monkeys. GTS-21 bound to human alpha 4
      beta 2 nAChR (K1-20 nM) 100-fold more potently than to human alpha 7 nAChR, and
      was 18- and 2-fold less potent than (-)-nicotine at human alpha 4 beta 2 and
      alpha 7 nAChR, respectively. Functionally. GTS-21 stimulated [5H]dopamine release
      from rat striatal slices with an EC50 of 10 +/- 2 microM (250-fold less potent
      and 70% as efficacious as (-)-nicotine), an effect blocked by the nAChR
      antagonist dihydro-beta-erythroidine. However, GTS-21 did not stimulate human
      alpha 4 beta 2 nor human ganglionic nAChRs significantly. In vivo, GTS-21 had no
      adverse effect on dog blood pressure (< or = 2.5 micromol/kg i.v. bolus
      infusion), in marked contrast with (-)-nicotine, GTS-21 (-62 micromol/kg.s.e.)
      also did not cross-discriminate significantly with (-)-nicotine in rats and did
      not reduce temperature or locomotion in mice. Neither was it active in the
      elevated plus maze anxiety model (0.19-6.2 micromol/kg.IP) in normal mice.
      However, GTS-21 did improve learning performance of monkeys in the delayed
      matching-to-sample task (32-130 nmol/kg.i.m.).

PMID- 9164578
TI  - Tremulous characteristics of the vacuous jaw movements induced by pilocarpine and
      ventrolateral striatal dopamine depletions.
AB  - Vacuous jaw movements induced by the muscarinic agonist pilocarpine and striatal
      dopamine depletions were examined using a slow motion videotape system. With this
      procedure, rats were videotaped in a Plexiglas tube so that the profile of the
      head region could be seen. Vacuous jaw movements were analyzed by examining the
      tape at 1/6 normal speed. An observer recorded each jaw movement using a
      computer, and the computer program re-calculated the temporal characteristics of
      jaw movement responses back to normal speed. The interresponse time was recorded
      for each jaw movement, and each jaw movement interresponse time was assigned to a
      50 ms wide time bin. Thus, the distribution of interresponse times could be used
      to analyze the temporal characteristics of jaw movement responses. In the first
      experiment, rats were administered saline vehicle, 1.0 mg/kg and 2.0 mg/kg
      pilocarpine. The rats were videotaped 10-15 min after injection, and the data
      were analyzed as described above. Pilocarpine induced very high levels of vacuous
      jaw movements, and the vast majority of all movements occurred in "bursts" with
      interresponse times of 1.0 s or less. Analysis of the interresponse time
      distributions showed that most of the jaw movements were within the 150-350 ms
      range. The modal jaw movement interresponse time was in the 150-200 ms range,
      which corresponds to a local frequency of 5-6.66 Hz. In the second experiment,
      the neurotoxic agent 6-hydroxydopamine was injected directly into the
      ventrolateral striatum in order to produce a local dopamine depletion. The
      dopamine-depleted rats were observed for jaw movements 7 days after surgery. The
      overall level of jaw movement activity resulting from dopamine-depletion was much
      lower than that produced by pilocarpine. There was a significant inverse
      correlation between ventrolateral striatal dopamine levels and total number of
      vacuous jaw movements. Videotape analysis indicated that the temporal
      characteristics of jaw movements induced by dopamine depletions were similar to
      those shown with pilocarpine. These experiments indicate that vacuous jaw
      movements induced by pilocarpine and striatal dopamine depletion occur in a
      frequency range similar to that shown in parkinsonian tremor.

PMID- 9164579
TI  - Facilitation of passive avoidance response by newly synthesized cationized
      arginine vasopressin fragment 4-9 in rats.
AB  - The effects of a newly synthesized cationized arginine vasopressin fragment 4-9
      analogue (C-AVP-(4-9)) on learning and memory in rats were studied by the passive
      avoidance test. C-AVP-(4-9) and its parent peptide, arginine vasopressin fragment
      4-9 (AVP-(4-9)), a well known potent neuropeptide, were subcutaneously injected
      1.5 hr prior to the retention test. The most effective doses of C-AVP-(4-9) and
      AVP-(4-9) were 8.6 x 10(-2) and 1.3 nmol/kg, respectively. To evaluate the
      distribution of C-AVP-(4-9) in the control nervous system (CNS), apparent tissue
      plasma concentration rations (Kp.app) of intravenously administered
      radioiodinated C-AVP-(4-9) (125I-C-AVP-(4-9)) in the CNS in mice were determined.
      At the apparent steady state of plasma concentration of 125I-C-AVP-(4-9), the
      Kp.app values of the 125I-C-AVP-(4-9) in the cerebrum, cerebellum and spinal cord
      were over 12 times higher than that of the vascular space marker which slightly
      penetrates the BBB. Moreover, the rat cerebral homogenate converted C-AVP-(4-9)
      into its parent peptide AVP-(4-9). These results suggest that the potent effects
      of C-AVP-(4-9) on learning and memory may be due to AVP-(4-9) generated as a
      result of distribution and metabolism of peripherally administered C-AVP-(4-9) in
      the CNS.

PMID- 9164580
TI  - Noradrenergic DSP-4 lesions aggravate impairment of working memory produced by
      hippocampal muscarinic blockade in rats.
AB  - To clarify the interactions between hippocampal cholinergic and adrenergic
      systems in working memory function of rats, the effects of hippocampal muscarinic
      receptor blockade combined with noradrenaline depletion on this behavior were
      examined with a three-panel runway task. Intrahippocampal administration of the
      muscarinic receptor antagonist scopolamine at a dose of 3.2 micrograms/side
      significantly increased the number of errors (attempts to pass through two
      incorrect panels of the three panel-gates at four choice points) in the working
      memory task, whereas the 0.32 microgram/side dose of scopolamine did not affect
      working memory errors. Administration of the noradrenergic neurotoxin N-(2
      chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) at 50 mg/kg IP caused a marked
      reduction in hippocampal noradrenaline concentration, but it had no effect on
      working memory errors. Intrahippocampal administration of 0.32 microgram/side
      scopolamine, the behaviorally ineffective dose in intact rats, significantly
      increased the number of working memory errors in the noradrenaline-depleted
      animals. These results suggest that hippocampal muscarinic/noradrenergic
      interactions are involved in neural processes mediating working memory function
      of rats.

PMID- 9164581
TI  - Intrahippocampal administration of lead (Pb) impairs performance of rats in the
      Morris water maze.
AB  - We examined spatial learning in the Morris water maze after daily acute bilateral
      micro-injection of 13.9 ng sodium acetate (NaAc) or 37.9 ng lead acetate (PbAc)
      in 1 microliter volumes into the dorsal hippocampus of normal adult rats. After
      six days of injections and water maze training, rats injected with NaAc were able
      to find a hidden platform in 8.3 s, and those injected with PbAc were
      significantly slower (15.2 s; p < 0.02). In a second experiment, rats were
      trained to find a hidden platform before injections began and then tested in
      order to determine if intrahippocampal injections of Pb affected the recall of a
      previously learned task. The escape latency on the first day after injections
      began was increased slightly when compared to the last day of training before
      injections, however the NaAc and PbAc groups were not significantly different
      over three days of injections. Both treatment groups performed as well as they
      did before injections began by the second day of injections. These results
      suggest that the direct injection of Pb into the hippocampus impairs the
      acquisition but not the recall of the spatial learning task in the Morris water
      maze.

PMID- 9164582
TI  - Age-dependent effects of developmental lead exposure on performance in the Morris
      water maze.
AB  - The neurobehavioral toxicity of developmental exposure to lead (Pb) was
      investigated by conducting tests of spatial learning in the Morris water maze.
      Female Long-Evans rats were exposed to 0 or 250 ppm Pb acetate in the diet
      beginning 10 days prior to breeding and continued throughout gestation and
      lactation. Pups were weaned onto the same diets as the dams at postnatal day 20
      (PN20). Increased levels of Pb were detected in the hippocampus of the 250 ppm Pb
      acetate group relative to controls. The highest concentration of Pb measured in
      the hippocampus was at PN21 with decreasing levels at older ages. In the Morris
      Water Maze, a statistically significant (p < 0.03; female rats) or near
      significant (p < 0.07; male rats) increase in the time required to find the
      hidden platform (escape latency) was observed when Pb-treated rats were tested in
      a reference memory paradigm. This effect was only observed when rats were tested
      at PN21 and not at older ages. No significant effects of developmental Pb
      exposure were measured when rats were tested in a working memory paradigm of the
      Morris water maze at any age. These initial studies indicate an impairment of
      performance in the swim task in PN21 rats exposed to Pb during development. The
      age-dependent effect of Pb in this learning paradigm is consistent with previous
      studies in experimental animals and with the observation that children are more
      susceptible to Pb-induced cognitive deficits than adults. The Morris water maze
      may be useful for studying the effects of Pb on learning and memory, and their
      neurochemical basis.

PMID- 9164583
TI  - Effects of the alpha 1a-adrenoceptor antagonist RS-17053 on phenylpropanolamine
      induced anorexia in rats.
AB  - Activation of alpha 1-Adrenergic receptors via systemic administration of drugs
      such as phenylpropanolamine (PPA) and cirazoline results in the suppression of
      feeding in rats. Whether PPA acts via activation of the three currently
      identified alpha 1-Adrenoceptor subtypes is unknown. The intent of the present
      study was thus to examine the effects of systemic administration of the novel
      alpha 1a-Adrenoceptor antagonist RS-17053 on PPA-induced anorexia. Adult male
      rats (n = 6 to 8 per group) were pretreated (IP) with either 0, 0.1, 0.5, 2.5, or
      10.0 mg/kg RS-17053 or with 2.0 mg/kg of the prototypical alpha 1-Adrenoceptor
      antagonist prazosin. Five minutes later, each rat was treated (IP) with either 0,
      5, 10 or 15 mg/kg PPA. Food and water intakes were recorded for a 30 min period
      starting 10 min after the the treatment injection. Rats pretreated with vehicle
      and then treated with PPA exhibited a dose-dependent suppression of feeding with
      a maximal effect evident at the 15 mg/kg dose of PPA. Pretreatment with 2.0 mg/kg
      prazosin reversed the anorexic activity of PPA. Pretreatment with RS-17053 (0.1
      2.5 mg/kg) did not alter either baseline feeding or the anorexic action of PPA.
      These results suggest that PPA does not act via the alpha 1a-Adrenergic receptor
      subtype to suppress food intake.

PMID- 9164584
TI  - Majonoside-R2, a major constituent of Vietnamese ginseng, attenuates opioid
      induced antinociception.
AB  - The effects of majonoside-R2 on antinociceptive responses caused by the mu-opioid
      receptor agonist morphine and the selective kappa-opioid receptor agonist U-50,
      488H were examined by the tail-pinch test in mice. Intraperitoneal (IP) or
      intracerebroventricular (ICV) injection of majonoside-R2 (3.1-6.2 mg/kg, IP or 5
      10 micrograms/mouse, ICV) and diazepam (0.1-0.5 mg/kg, IP or 0.5-1.0
      microgram/mouse, ICV), as well as an opioid receptor antagonist naloxone (2
      mg/kg, IP or 5 micrograms/mouse, ICV), dose-dependently attenuated the
      antinociception caused by subcutaneously administered morphine and U-50,488H.
      Moreover, when co-administered ICV or intrathecally (IT) with morphine (4
      micrograms/mouse) or U-50,488H (60 micrograms/mouse), majonoside-R2 (5-20
      micrograms/mouse) also exhibited antagonism against the antinociceptive action of
      these opioid receptor agonists in the tail-pinch test. The inhibitory effects of
      majonoside-R2 (10 micrograms/mouse, ICV) and diazepam (1 microgram/mouse, ICV)
      were reversed by flumazenil (2.5 micrograms/mouse, ICV), a selective
      benzodiazepine receptor antagonist, and picrotoxin (0.25 microgram/mouse, ICV), a
      GABA-gated chloride channel blocker. These results suggest that majonoside-R2
      attenuates the opioid-induced antinociception by acting at the spinal and
      supraspinal levels, and that the GABAA receptor complex at the supraspinal level
      is involved in the effect of ICV administered majonoside-R2.

PMID- 9164585
TI  - Involvement of delta 1 and delta 2 opioid receptor subtypes in the development of
      physical dependence on morphine in mice.
AB  - The effects of the highly selective delta opioid receptor antagonists naltrindole
      (NTI) for delta 1 and delta 2 naltriben (NTB) and naltrindole 5'-isothiocyanate
      (5'-NTII) for delta 2 and 7-benzylidenenaltrexone (BNTX) for delta 1 on the
      development of physical dependence on morphine were investigated in mice. Neither
      NTI (3 mg/kg, sc), NTB (0.5 mg/kg, sc), 5'-NTII (0.5 mg/kg, sc) nor BNTX (0.5
      mg/kg, sc) suppressed the antinociception induced by morphine (10 mg/kg, sc).
      Pretreatment with NTI (3 mg/kg, sc), NTB (0.5, 1.0 mg/kg, sc) or 5'-NTII (0.5,
      1.0 mg/kg, sc) during chronic treatment with morphine for 5 days significantly
      suppressed naloxone-induced body-weight loss in morphine-dependent mice. The
      incidence of jumping and body shakes in morphine-dependent mice that were
      pretreated with NTI. NTB or 5'-NTII were significantly lower than with morphine
      alone. Pretreatment with BNTX (0.5, 1.0 mg/kg, sc) during chronic treatment with
      morphine also significantly suppressed naloxone-induced body-weight loss in
      morphine-dependent mice, but this suppression was weaker than that by the
      antagonists. In contrast to mice that had been pretreated with NTI, NTB or 5'
      NTII, the incidence of several withdrawal signs, such a jumping and body shakes,
      was not significantly affected in morphine-dependent mice that were pretreated
      with BNTX. These findings suggest that both delta 2 and delta 1 opioid receptors
      may play important roles in modulating the development of physical dependence on
      morphine.

PMID- 9164586
TI  - The 5-HT1A receptor antagonist p-MPPI blocks responses mediated by postsynaptic
      and presynaptic 5-HT1A receptors.
AB  - The present experiments examined the ability of the novel 5-HT1A receptor
      antagonist to block responses mediated by postsynaptic and presynaptic 5-HT1A
      receptors in vivo. Pretreatment with p-MPPI reduced or blocked the effect of the
      5-HT1A receptor agonist 8-OH-DPAT on two responses mediated by postsynaptic 5
      HT1A receptors, reduction of body temperature and the 5-HT behavioral syndrome.
      Administration of p-MPPI alone did not alter body temperature or produce symptoms
      of the 5-HT syndrome. Pretreatment with p-MPPI also blocked the ability of 8-OH
      DPAT to reduce extracellular 5-HT in the striatum, a response mediated by
      presynaptic 5-HT1A receptors in the dorsal raphe nucleus, but did not alter
      striatal 5-HT when administered alone. These results indicate that p-MPPI is an
      effective 5-HT1A receptor antagonist in vivo with no intrinsic activity. p-MPPI
      may prove to be a useful pharmacological tool for studying 5-HT1A receptors and
      their involvement in anxiety and affective disorders.

PMID- 9164587
TI  - Ethanol and cocaine intake by rats selectively bred for oral opioid acceptance.
AB  - Lines which accept or reject the potent opioid etonitazene, and a randomly bred
      control line, were assessed for the specificity of selective breeding. Drug-naive
      subjects from generation 8 were offered a continuous choice between water and 10%
      ethanol for 20 days. There was no difference between the accepting and rejecting
      lines in preference for one fluid, or in amount of ethanol consumed. The same
      rats were then given a choice between water and increasing concentrations (0.08
      0.64 mg/ml) of cocaine, 7 days at each concentration. There were no differences
      among the lines in preference for the drug, but the rejecting line drank more of
      the cocaine solution than the accepting line. Finally, these rats were subjected
      to the regimen used in choosing rats for selective breeding, 4 days of a water
      etonitazene choice. In their preference for etonitazene the order of the lines
      was as expected: accepting > control > rejecting. In addition, the accepting line
      drank more of the etonitazene solution than the other two lines. These data
      suggest that selection has been rather specific and not for a generalized
      tendency to become intoxicated.

PMID- 9164588
TI  - Inbred mouse strains differ in sensitivity to "popping" behavior elicited by MK
      801.
AB  - We examined possible genetic contributions to MK-801-elicited "popping" behavior
      in mice. MK-801-elicited "popping" behavior may represent a preclinical screening
      paradigm for identifying novel antipsychotic medications. Specifically, we
      studied the sensitivity of four inbred strains of mice (BALB/c, C57BL/6, AKR, and
      DBA/2) to MK-801-elicited "popping" behavior and compared their response to the
      outbred NIH Swiss strain in which the behavior was first characterized. The
      BALB/c strain was most sensitive to the elicitation of MK-801 induced popping
      behavior, whereas the other inbred strains were less sensitive than the outbred
      strain. The identification of strain differences in MK-801-elicited "popping"
      behavior suggests an important role for genetic factors in the elicitation of MK
      801 "popping" behavior in mice.

PMID- 9164589
TI  - Suppressive effect of mitragynine on the 5-methoxy-N,N-dimethyltryptamine-induced
      head-twitch response in mice.
AB  - We investigated the effects of mitragynine, a major alkaloid isolated from the
      leaves of Mitragyna speciosa Korth (Rubiaceae), on the 5-HT2A receptor-mediated
      head-twitch response in mice. Intraperitoneal injection of mitragynine (5-30
      mg/kg), as well as intraperitoneal injection of 5-HT2A receptor antagonist
      ritanserin, inhibited the 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT: 16 mg/kg,
      IP)-induced head-twitch response in a dose-dependent manner. In contrast,
      mitragynine affected neither head-weaving caused by 5-MeO-DMT, nor drug-free
      spontaneous motor activity. Pretreatment of mice with reserpine (5 mg/kg, IP), p
      chlorophenylalanine (p-CPA, 300 mg/kg x 3 times, IP), or 6-hydroxydopamine (6
      OHDA, 50 micrograms/mouse, ICV) plus nomifensine (5 mg/kg, IP) did not change the
      suppressant effect of mitragynine on the head-twitch response caused by 5-MeO
      DMT. On the other hand, the alpha 2-adrenoceptor antagonists yohimbine (0.5
      mg/kg, IP), and idazoxan (0.2 mg/kg, IP), significantly attenuated the
      suppressant effect of mitragynine. Lesion of central noradrenergic systems by 6
      OHDA plus nomifensine did not alter the effect of idazoxan (0.2 mg/kg) on
      mitragynine-induced suppression of the head-twitch response. These results
      indicate that stimulation of postsynaptic alpha 2-adrenoceptor, blockade of 5
      HT2A receptors, or both, are involved in suppression of 5-HT2A receptor-mediated
      head-twitch response by mitragynine.

PMID- 9164590
TI  - Effects of 5-HT3, D1 and D2 receptor antagonists on ethanol- and cocaine-induced
      locomotion.
AB  - The effects of acute treatment with 5-HT3 receptor antagonists, ondansetron and
      ICS 205-930, on the stimulation of activity induced by ethanol-and cocaine were
      examined. Ethanol (1.8 or 2 g/kg i.p.) or cocaine (15 mg/kg i.p.) produced a
      significant increase in locomotor activity (LMA) in DBA/2N mice. Pretreatment
      with ondansetron or ICS 205-930, in doses ranging from 0.001 to 0.1 mg/kg (s.c),
      did not modify ethanol or cocaine induced stimulation of activity. In contrast,
      pretreatment with a 10 micrograms/kg dose of either SCH 23390 or spiperone, a D1
      and D2 dopamine (DA) receptor antagonist respectively, completely antagonized the
      stimulation of LMA induced by ethanol. Similar dose of SCH23390, but not
      spiperone, blocked the stimulation of activity induced by cocaine. These results
      indicate that D1 but not D 2 DA receptors play a significant role in cocaine
      induced hyperactivity whereas both D1 and D2 are involved the locomotor
      activating effects of ethanol.

PMID- 9164591
TI  - Effects of d-amphetamine in grouped versus isolated humans.
AB  - This study was designed to determine whether the subjective, behavioral or
      physiological effects of a stimulant drug in humans depend on whether subjects
      are tested under isolated or social conditions. Forty-two subjects were randomly
      assigned to either the Social (SOC) or Isolated (ISO) condition. SOC subjects
      participated in 4 h laboratory sessions in groups of 3 or 4, whereas ISO subjects
      participated in the sessions alone. All subjects participated in three sessions,
      during which they received capsules containing d-amphetamine (10 or 20 mg) or
      placebo, in mixed order under double blind conditions. Subjective, physiological
      and behavioral measures were obtained at regular intervals, d-amphetamine
      produced dose-related, prototypic stimulant effects on many measures, including
      self-reported mood states, behavioral indices and physiological measures. Most of
      these effects were unaffected by the setting in which subjects were tested (SOC
      vs ISO). However, body temperature was overall higher in the SOC group, and there
      was a trend for d-amphetamine to produce greater hyperthermic effects in the SOC
      group. In addition, 10 mg d-amphetamine increased heart rate in the SOC group but
      not in the ISO group. The results suggest that, like in laboratory animals, some
      of the effects of stimulants in humans are greater under aggregated conditions.
      However, unlike in the animal studies, this observed enhancement of the drug's
      effects under aggregated conditions was limited to physiological measures and did
      not apply to other subjective or behavioral measures.

PMID- 9164592
TI  - Induction of sensitization to hyperactivity caused by morphine in mice: effects
      of post-drug environments.
AB  - Mice given five repeated administrations of morphine (10 mg/kg sc) at 3 day
      intervals in a round tilting-type activity cage (20 cm in diameter) or round
      spaces 15-30 cm in diameter with fixed floor showed almost the same level of
      ambulatory sensitization to morphine. Whereas, mice given morphine in the same
      schedule in spaces 4 and 12 cm, but not 6 and 9 cm, in diameter demonstrated a
      partial increase in the sensitivity to morphine. Furthermore, mice given morphine
      five times in a transparent cage (20W x 25L x 15H cm) with woodchip bedding, that
      was the same as the home cage, showed a weak and strong ambulatory sensitization
      when they were placed in group of ten and singly, respectively, for 3 h after
      each morphine administration. Repeated administrations of saline to mice in the
      space 4 cm in diameter resulted in increased sensitivity to morphine. However,
      the pretreatment with saline in the other environments (activity cage, spaces 6
      30 cm in diameter with fixed floor, and home cage-like cage in which mice were
      placed singly or in group of ten) did not change the sensitivity to morphine.
      These results suggest that repeated experience of pharmacological effect of
      morphine and the resultant ambulation is one of the most important factors for
      induction of strong ambulatory sensitization to morphine in mice. It is estimated
      that a space 15 cm in diameter, which corresponds to 2-2.5 times as long as the
      body length without tail is a minimum requirement for induction of strong
      ambulatory sensitization to morphine. In contrast, even though mice are placed in
      a sufficient space for ambulation, an interference of ambulation by the other
      mice acts to inhibit the induction of ambulatory sensitization. It is also
      suggested that a strong stress caused by restraint is responsible for significant
      increase in sensitivity to morphine.

PMID- 9164594
TI  - Captopril alters schedule induced polydipsia, urination, and defecation in rats.
AB  - Schedule induced polydipsia, urination and defecation were examined in rats that
      received training on a fixed interval 2 min schedule of food reinforcement. In
      Phase I of the experiment, animals received peripheral injections of captopril
      (an angiotensin conversion enzyme blocker, 0.5 or 50 mg/kg), or equivalent
      volumes of 0.9% saline. The results showed that low doses of captopril (0.5
      mg/kg) significantly increased both operant responding and the adjunctive
      behaviors. High peripheral doses of captopril significantly reduced responding
      and schedule induced behavior. In Phase II of the experiment, animals received
      either low peripheral doses of captopril (sc 0.5 mg/kg), or low doses that were
      coupled with central injections (i.e., 0.12 mg icv + 0.5 mg/kg sc). As observed
      in Phase I, low peripheral doses of captopril enhanced behavior, but the
      enhancement effect was eliminated with low (0.12 mg) central administration. The
      overall results are consistent with past research examining captopril effects on
      non-operant, meal-induced drinking. Yet since captopril affected operant
      responding and adjunctive behaviors similarly, the findings suggest that
      angiotensin plays a common role in the motivational processes that precede and
      follow the arrival of food.

PMID- 9164593
TI  - Nitric oxide synthase inhibition impairs spatial navigation learning and induces
      conditioned taste aversion.
AB  - The free radical gas nitric oxide (NO) is formed from the amino acid precursor L
      arginine in brain regions which are associated with learning and the formation of
      memory. We have previously reported that administration of the nitric oxide
      synthase (NOS) inhibitor N omega-nitro-L-arginine methyl ester (L-Name) impairs
      delayed recall in non-human primates but that, at higher doses, impairment is
      associated with aversive gastrointestinal side effects. The purpose of the
      present study was to examine the effects of L-Name on learning in a rat spatial
      navigation task and to assess the ability of L-Name to induce a conditioned taste
      aversion (CTA) to a novel sucrose solution in a two-bottle choice paradigm. In
      the Morris water maze. L-Name (5, 20, and 50 mg/kg) markedly impaired cued
      spatial learning required to locate a hidden platform on three consecutive days
      of testing, but did not affect general activity levels. These data also
      demonstrated the ability of L-Name to induce a potent CTA, though only with the
      20 and 50 mg/kg doses. Both the impairment of learning and CTA were blocked by
      administration of a mole equivalent dose of L-arginine, indicating that
      attenuated NO activity was associated with both behavioral effects. These data
      demonstrate that inhibition of NO activity by L-Name induces significant and
      selective impairment of cognitive performance at low pharmacologic doses (< 20
      mg/kg). However, with higher doses of NOS inhibitors, impairment may be a
      secondary effect of drug-induced malaise, possibly related to peristaltic
      dysregulation of gastrointestinal musculature. Therefore, conclusions as to the
      mediation of learning and memory processes by CNS NO may be difficult to
      interpret without the use of selective, centrally-acting compounds.

PMID- 9164595
TI  - Effects of dopamine antagonists on changes in spontaneous EEG and locomotor
      activity in ketamine-treated rats.
AB  - We investigated the effects of dopamine antagonists on spontaneous cortical and
      hippocampal electroencephalographic (EEG) changes, and on hyperlocomotion in
      ketamine-treated rats. Ketamine (20-60 mg/kg IP) synchronized cortical EEG and
      desynchronized hippocampal EEG in a dose-dependent manner indicating that the
      drug induced a dissociation between the cortical and hippocampal EEG. These EEG
      changes were accompanied by an increase in spontaneous locomotor activity, which
      involved lack of focused direction, stereotypy, irritability and other
      abnormalities. Dopamine antagonists, such as haloperidol (0.3-1 mg/kg IP), and
      nemonapride (0.3-1 mg/kg IP), reversed the dissociation between the cortical and
      hippocampal EEG in ketamine (60 mg/kg IP)-treated rats. Ketamine-induced
      hyperlocomotion was also decreased by administration of haloperidol (0.3 and 1
      mg/kg IP) or nemonapride (0.1-1 mg/kg IP). Thus, it was found that dopamine
      antagonists reversed the EEG alterations and behavioural changes in ketamine
      treated rats.

PMID- 9164596
TI  - Behavioral and electroencephalographic studies of beagles with an Eck's fistula:
      suitability as a model of hepatic encephalopathy.
AB  - Behavioral manifestations, electroencephalograms (EEGs) and visually evoked
      potentials (VEPs) were studied in beagles with Eck's fistula (portacaval shunt
      [PCS]), an established model of hyperammonemia, to determine whether they
      developed CNS disorders characteristic of hepatic encephalopathy. After PCS,
      behavioral changes occurred in the form of listlessness, sluggishness (altered
      gait, snapping and transient catatonia-like symptoms) and apparent blindness,
      which appeared in that order and progressed to coma and death in some animals.
      The EEGs from the frontal cortex showed a gradual decrease in voltage and
      frequency. Development of snapping and catatonia-like symptoms coincided with the
      occurrence of high voltage fast waves in the EEGs from the occipital cortex. In
      comatose Eck's fistula dogs. flattening of the EEGs was recorded from the frontal
      cortex and a lowered voltage was noted in the EEGs from the occipital cortex.
      After PCS, the latencies and amplitudes of the components of VEP were increased.
      The snapping and catatonia-like symptoms were markedly ameliorated by
      carbamazepine and the coma by flumazenil and thyrotropin-releasing hormone. These
      findings indicate that Eck's fistula dogs provide a useful model of hepatic
      encephalopathy.

PMID- 9164597
TI  - Prior exposure to palatable solutions enhances the effects of naltrexone on food
      intake in rats.
AB  - Previous research has suggested that chronic intake of palatable foods and fluids
      enhances the activity of the endogenous opioid system. To examine this
      suggestion, the effect of naltrexone on food intake was examined in male Long
      Evans rats with or without prior exposure to palatable solutions. In Experiment
      1, rats were fed laboratory chow alone or laboratory chow and a 32% sucrose
      solution, and in Experiment 2, were fed chow alone, chow and a 32% Polycose
      solution, or chow and a 0.15% saccharin solution for three weeks. The sucrose,
      Polycose, and saccharin solutions were removed 18 h prior to drug administration.
      Rats then received injections of naltrexone hydrochloride (0.0, 0.3 or 3.0 mg/kg.
      sc) and chow intakes were measured during the subsequent 1, 2, 4, 6 and 24 h.
      Naltrexone injections had minimal effects on intakes of animals which previously
      had consumed only chow. In contrast, naltrexone led to significant dose-related
      decreases in chow intakes in rats which had previously consumed the sucrose,
      Polycose, or saccharin solutions. These results provide confirmation for the
      suggestion that chronic intake of palatable solutions alters the activity of the
      endogenous opioid system.

PMID- 9164598
TI  - Deficits in water escape performance and alterations in hippocampal cholinergic
      mechanisms associated with neonatal monosodium glutamate treatment in mice.
AB  - Mice treated neonatally with monosodium glutamate (MSG) were found to have
      learning and memory deficits in performing a non-spatial water escape task.
      Scopolamine impaired the water-escape performance of the control mice but not
      that of the MSG-treated mice. It was suggested that the water-escape performance
      deficit in the MSG-treated mice was a result of impaired central cholinergic
      mechanisms. As such, scopolamine was unable to further incapacitate an already
      impaired cholinergic system. This is strongly supported by the decreased affinity
      of the sodium-dependent high-affinity choline uptake observed in the hippocampus.
      D-Cycloserine, a partial agonist at the glycine site of the NMDA receptor, did
      not affect the water-escape performance of the MSG-treated and control mice; nor
      did it alter the effects of scopolamine. This lack of effect of D-Cycloserine may
      imply that the NMDA receptors are not involved in non-spatial learning, in
      contrast to their reported involvement in spatial learning.

PMID- 9164599
TI  - Influenza virus infection of mice induces anorexia: comparison with endotoxin and
      interleukin-1 and the effects of indomethacin.
AB  - The effects of infection of mice with influenza virus on ingestive behavior were
      assessed by both 22-h intake of food pellets, and intake of sweetened milk in a
      30-minute access period. Infection with a lethal dose of virus resulted in losses
      in body weight as well as a reduction in food pellet intake. By contrast,
      infection with a sublethal dose of virus decreased body weight and food pellet
      intake to a lesser extent, but did not alter milk intake. Acute intraperitoneal
      injection of endotoxin (LPS, 0.3-5 micrograms), interleukin-1 alpha (IL-1 alpha,
      50-100 ng) or IL-1 beta (100 ng) reduced milk intake, suggesting that the
      reduction of ingestive behavior may be associated with immune activation in
      general, and IL-1 in particular Pretreatment of the mice with the cyclooxygenase
      inhibitor, indomethacin (10 mg/kg SC) substantially attenuated, but did not
      completely reverse, the reduction in milk intake by LPS and IL-1. However,
      chronic treatment with indomethacin failed to alter the body weight or the intake
      of sweetened milk in influenza-infected mice, although there was some attenuation
      of the reduction in food intake. These results suggest that although IL-1 may
      play a role in the anorexia caused by influenza virus infection, it is not the
      only factor involved.

PMID- 9164600
TI  - Cumulative vs. acute dose-response procedures produce differential BAC and
      behavioral functions for ethanol.
AB  - The discriminative stimulus attributes of ethanol (ETOH) were characterized in
      rats trained to discriminate between 1.25 g/kg ETOH and saline. The ETOH
      generalization functions were assessed using both acute and cumulative dosing
      procedures. The cumulative procedures differed in the individual incremented
      doses used to generate the functions. Acute dosing procedures produced
      discriminative functions that were significantly different from cumulative dose
      response curves (DRCs). Similar cumulative DRC's were generated within each
      cumulative dosing procedure, whereas significant differences were produced
      between the two dosing incremented procedures. When blood alcohol concentrations
      (BACs) were quantified, a cumulative testing procedure produced significantly
      lower BACs than acute testing procedures at every dose above the initial or
      starting dose. Interestingly, response rate functions did not differ within or
      between cumulative and acute procedures. These data may suggest that differential
      ETOH dosing procedures may differentially influence the behavioral choice and BAC
      functions in rats, and cautions against the use of cumulative procedures to
      assess shifts in DRCs during chronic treatments without a concomitant assessment
      of BACs.

PMID- 9164601
TI  - Fine epitope specificity of antibodies to region II of the Plasmodium vivax
      circumsporozoite protein correlates with ability to bind recombinant protein and
      sporozoites.
AB  - Recent work has suggested that important B- and T-cell epitopes on the
      circumsporozoite protein (CSP) of Plasmodium vivax lie external to the major
      repeat regions of the protein. We have studied two naturally exposed human
      populations (Caucasian and Papua New Guineans) and determined the antibody
      response to yeast-derived recombinant CSPs, overlapping synthetic peptides
      spanning amino acids 76 348 of the Belem P. vivax CSP and overlapping peptides
      representing the variant repeats of the VK247 strain of P. vivax. We have
      demonstrated that the P. vivax CSP-specific antibody response is directed towards
      areas within the repeat region as well as areas external to this; but the
      dominant epitopes recognized by the two populations studied, were distinct. One
      epitope, lying external to the repeats and recognized by both populations,
      partially overlaps an area of the protein referred to as region II-plus. Sera
      from malaria-exposed Papua New Guineans and Thais contained antibodies to this
      epitope (V22, single letter amino acid sequence TCGVGVRVRRRVNAANKKPE) which were
      capable of recognizing sporozoites, as determined by quantitative inhibition IFA.
      Seventeen percent of PNG sera had antibodies to this peptide compared with 33%
      who had antibodies to the central repeats of the protein. Immunization of mice
      with recombinant CSP did not induce antibodies to V22. However, immunization with
      overlapping peptide epitopes representing this region (V21 or V22) induced
      specific antibodies but only two sera recognized both V21 and V22 and, by
      inference, the overlapping peptide sequence (TCGVGVRVRR). Antibodies in these two
      sera could bind recombinant CSP in ELISA; however, in contrast, nine sera which
      recognized either V21 or V22 alone did not bind CSP. Only one of two sera
      containing antibodies recognizing CSP stained P. vivax sporozoites. This serum
      also recognized an epitope dependent upon two amino acids aminoterminal to V22.
      These data suggest that the fine specificity of antibodies is a critical
      determinant for binding to both recCSP and sporozoites.

PMID- 9164602
TI  - The daily feeding rate of tsetse (Diptera: Glossinidae) on cattle at Galana
      Ranch, Kenya and comparison with trypanosomiasis incidence.
AB  - At Galana Ranch, south-eastern Kenya, for 2 days each month from January to May
      1993. Glossina pallidipes and G. longipennis were sampled around a heifer for 30
      min every hour from 06:00 to 19:00. There was a seasonal decline in tsetse
      abundance; estimates of the total number attracted to the heifer in 1 day ranged
      from 556 G. pallidipes in January to 0 in May and 122 G. longipennis in February
      to 27 in May. The number of tsetse estimated to have fed on the heifer in 1 day
      during peak months was 260 G. pallidipes and 15 G. longipennis. Trypanosome
      infection rates of tsetse, obtained from trapped flies, suggest that the heifer
      received 1.1 T. congolense and 2.2 T. vivax-infected bites per day in January but
      only 0.007 T. congolense and 0.047 T. vivax-infected bites per day in May. These
      predictions are compared with the observed incidence of trypanosomiasis in a
      nearby herd of cattle. There was a linear relationship between the estimated
      daily rate of infected flies feeding on the heifer and the incidence of
      trypanosomiasis the following month. The slope of this relationship suggests that
      the transmission efficiencies of T. congolense and T. vivax from tsetse to cattle
      are 0.84 and 2.36%, respectively, considerably lower than has been reported
      elsewhere. Possible reasons for this are discussed and it is suggested that
      previous estimates may be too high.

PMID- 9164603
TI  - Toxoplasma gondii: the growth characteristics of three virulent strains.
AB  - We have studied the phenotype of three mouse virulent strains of Toxoplasma
      gondii (RH, Martin and ENT), monitoring cellular factors which may relate to
      virulence. There was variation between these three strains in three separate
      criteria: invasion, growth and tachyzoite-bradyzoite interconversion. The ENT
      strain exhibited consistently higher invasion rates, a shorter doubling time and
      a lower frequency of bradyzoite production than Martin or RH strains. In addition
      to variation in growth rate, there were also differences in the morphology of the
      parasites, with the ENT strain exhibiting highly synchronous division giving rise
      to characteristic rosettes. The Martin strain produced bradyzoites at a higher
      frequency and, in culture, parasites were often seen in tight clusters, which
      were reminiscent of early tissue cysts. These phenotypic variations amongst mouse
      virulent strains of the parasite may imply underlying genetic differences within
      the group.

PMID- 9164604
TI  - The importance of cattle as a food source for Glossina morsitans morsitans Katete
      district, Eastern Province, Zambia.
AB  - The feeding habits of Glossina morsitans morsitans in the Eastern Province of
      Zambia were studied. A total of 687 meals were identified. Results show that
      75.1% of the meals were taken on cattle. These results are discussed in relation
      to the published data on feeding patterns of Glossina morsitans morsitans and the
      control of tsetse or tsetse-transmitted trypanosomosis in the study area.

PMID- 9164605
TI  - Engineering and expression of a full length cDNA encoding Schistosoma japonicum
      paramyosin. Purification of the recombinant protein and its recognition by
      infected patient sera.
AB  - A cDNA encoding the complete open reading frame of the Schistosoma japonicum
      paramyosin has been constructed and cloned. The 2600 bp cDNA was engineered by
      PCR using a N-terminally truncated paramyosin clone (pmy25) as template and a 57
      mer primer that introduced the eight missing amino acids and matched the 5'
      sequence of pmy25 in conjunction with a pmy specific reverse primer. After
      cloning and expression, the recombinant protein was purified by affinity
      chromatography under non-denaturing conditions and was shown to have a molecular
      mass of 99 kDa which is equivalent to the expected size of the full length
      recombinant fusion protein, comprising the 97 kDa paramyosin plus an additional 2
      kDa for the N-terminal fusion peptide incorporating the six histidine residues
      required for purification. In Western blot assays it reacted specifically with
      anti-paramyosin antibodies in sera from vaccinated animals and patients with
      Asian schistosomiasis. The engineering of the full-length cDNA encoding
      Schistosoma japonicum paramyosin, its bacterial expression and purification will
      facilitate future studies aimed at determining its efficacy as an anti
      schistosomiasis vaccine.

PMID- 9164606
TI  - Occupational therapy in home health: rapid changes need proactive planning.

PMID- 9164607
TI  - Evaluation of daily living tasks: the home care advantage.
AB  - Occupational therapists working in home care have an advantage over those working
      in other settings because they can observe the influence of the naturalistic
      context on task performance. However, to use this advantage, therapists working
      in home care must use an evaluation approach that enables them to capture the
      client-task-context transaction. In this article, we discuss the ability of four
      "evaluation approaches"--norm-referenced, criterion-referenced, dynamic, informal
      -to provide information about the client-task-context transaction that therapists
      need in order to plan effective intervention. The potential of each approach for
      identifying clients' performance problems, suggesting etiologies, determining
      rehabilitation potential, and guiding intervention is analyzed, and the
      appropriateness of each approach for application in the home is appraised. This
      analysis highlights the utility of combining the criterion-referenced and dynamic
      assessment approaches for use in home care. A sequential process for integrating
      these two approaches is provided, and the proposed outcomes to be obtained from
      this process are identified.

PMID- 9164608
TI  - A description of fieldwork in the home care setting.
AB  - There are few opportunities for fieldwork education in the home health setting
      and no available references or resources for establishing a home health fieldwork
      program. Home health practice involves issues that must be considered when
      establishing a fieldwork program. These issues include the focus or content of
      the fieldwork experience, supervision requirements and logistics, and how time is
      used and structured. This article describes a program that offers Level II
      fieldwork in home care. During the program refinements over the past 6 years,
      issues about content, supervision, and time use were addressed and resolved.
      Fieldwork in the home health setting prepares occupational therapy students for
      community practice and can increase their awareness of the issues clients face
      upon returning home after acute medical intervention. Fieldwork in home care also
      offers a partial solution to the shortage of fieldwork sites in which to train
      occupational therapy students.

PMID- 9164609
TI  - Moral tensions and obligations of occupational therapy practitioners providing
      home care.
AB  - Home care has been valued as a relevant context for the provision of occupational
      therapy since the inception of the field. The setting provides rich opportunities
      to restore meaningfulness in living for clients whose lives have been disrupted
      by illness or untoward events. Additionally the home care setting allows
      practitioners to exercise professional commitments and to meet ethical
      obligations congruent with the field of occupational therapy. Nevertheless, the
      home care arena is not exempt from the pressures that pervade the health care
      industry. To thrive in the provision of home care, occupational therapy
      practitioners must prepare themselves to deal with the philosophic, economic, and
      moral challenges inherent in the setting. This article explores the moral
      obligations of occupational therapy practitioners who provide home care. More
      specifically, it addresses obligations to self, to patients, to caregivers, to
      society, to the profession, to fellow health care providers, and to agencies and
      payers. Ethical principles associated with each are highlighted, and issues are
      raised. Home care practitioners who are attuned to the moral commitments imbedded
      in occupational therapy philosophy will most likely incorporate these tenets into
      their clinical decisions.

PMID- 9164610
TI  - Documenting progress in home care.
AB  - The home is an ideal environment for the practice of occupational therapy.
      However, the tumultuous health care environment of the late 1990s requires
      practitioners to take special care not only in delivering effective services, but
      also in documenting the delivery of skilled care. Documentation is the bridge
      between the delivery of occupational therapy services in the home and the
      approval for reimbursement of services by third-party payers. This article
      presents principles for writing reimbursable progress notes for home care that
      are based on Medicare documents related to occupational therapy. Application of
      these principles can improve efficiency and excellence in practitioners'
      documentation skills.

PMID- 9164611
TI  - OTR-COTA collaboration in home health: roles and supervisory issues.
AB  - This article describes the registered occupational therapist (OTR)-certified
      occupational therapy assistant (COTA) team within the home health setting. It
      reviews regulations and guidelines for supervision, team interactions, and
      collaboration with other health care professionals and paraprofessionals. With
      the complexities of providing treatment in a client's home, the team members must
      combine their resources to successfully achieve desired outcomes. The article
      addresses various areas in which quality OTR-COTA collaboration enhances therapy
      effectiveness in reaching established treatment goals in a realistic and creative
      manner.

PMID- 9164612
TI  - Performance context and its role in treatment planning.

PMID- 9164613
TI  - Outcome measurement in home health.
AB  - Home health occupational therapists, as well as their colleagues in other
      settings, cannot afford to ignore the need for clear, objective, and reliable
      outcome measurements. Such measurement will provide patients and payers with
      information on the value and quality of specific occupational therapy services
      and their overall value to various patient populations.

PMID- 9164614
TI  - How can competency in home health be addressed?

PMID- 9164615
TI  - What can be done about home health fieldwork?
AB  - The literature indicates that health care is moving away from institutional care
      and specialization to the community and home where providers need generalist
      competencies. As educators strive to prepare students for this environment,
      fieldwork experiences in the community and home are opportunities for students to
      develop generalist competencies. Because of the current scarcity of fieldwork
      sites, in general, scheduling placements is difficult. As educators seek new
      sites, home health settings and therapists who provide home health care as a
      component of their service need to be considered. Home health occupational
      therapy requires a practitioner to adopt a holistic perspective in order to
      assist clients to function optimally in their home environment. Because a large
      number of students work in addition to taking classes, they can be encouraged to
      find jobs as home health aides or chore providers as part-time employment before
      and during their didactic education. This work experience can help them to
      acculturate to the home setting. By encouraging students' participation in home
      health experiences, educators are helping to facilitate generalist competencies.

PMID- 9164616
TI  - Finding meaning in life.

PMID- 9164617
TI  - Combined endoscopic transnasal and transantral orbital decompression.

PMID- 9164618
TI  - Immunological potential of the tympanic membrane. Observation under normal and
      inflammatory conditions.
AB  - PURPOSE: The immunological potential of the murine tympanic membrane was studied
      under normal and inflammatory conditions. MATERIALS AND METHODS: Experimental
      otitis media was induced by injecting keyhole limpet hemocyanin into the tympanic
      cavity of systemically sensitized mice. The animals were killed from 1 day to 2
      weeks after the injection, and the distribution of the immunocompetent cells in
      the tympanic membrane was compared with those in normal animals, by
      immunohistochemical and toluidine blue staining. RESULTS: Tympanic membranes
      under normal conditions showed few immunocompetent cells, except mast cells and
      la-positive dendritic cells (presumably Langerhans' cells) in the pars flaccida
      and in the annular and manubrial regions of the pars tensa. After the induction
      of otitis media, lymphocytes migrated into these regions, although the other
      regions of the pars tensa showed few of these cells. la-positive cells migrated
      into both pars tensa and pars flaccida. Mast cells did not show obvious changes
      between the normal and inflammatory conditions. CONCLUSION: The pars flaccida and
      the annular and manubrial regions of the pars tensa are considered to be the
      immunologically potential sites, responsible for the immune responses. The
      remaining greater part of the tympanic membrane can recognize antigens by the
      migrated Langerhans' cells.

PMID- 9164619
TI  - Mitochondrial gene mutation is a significant predisposing factor in
      aminoglycoside ototoxicity.
AB  - PURPOSE: Aminoglycoside-induced deafness caused by mutations in the mitochondrial
      12S ribosomal RNA gene has been described in a number of Asian patients. The
      purpose of the current study is to analyze ethnically diverse patients in the
      United States with hearing loss after aminoglycoside exposure for presence or
      absence of these mitochondrial DNA mutations, and establish the frequency and
      clinical presentation associated with them. PATIENTS AND METHODS: Clinical
      histories, medical records, and blood samples were obtained from 41 unrelated
      American individuals with hearing loss after aminoglycoside exposure. DNA was
      extracted from the blood of these individuals, amplified by the polymerase chain
      reaction, and analyzed for mitochondrial ribosomal RNA gene mutations by allele
      specific oligonucleotide hybridization, restriction fragment length polymorphism
      analysis, and sequencing. RESULTS: The nucleotide 1555 A-->G mutation was
      identified in 7 of 41 individuals (17%). None of the other known mutations was
      found. The ethnic origin of the individuals with predisposing mutations included
      Caucasians, Hispanics, and Asians. Four of the 7 patients with the 1555 A-->G
      mutation had a family history of aminoglycoside-induced ototoxicity. Particularly
      unexpected was the late onset of hearing loss in 3 of these patients, years after
      the aminoglycoside exposure. The 12S ribosomal RNA gene was sequenced in these
      patients, and a second sequence change that could be responsible for the milder
      phenotype was detected in 1 of the 3 patients. CONCLUSION: These findings imply
      that a significant proportion of patients with aminoglycoside-induced ototoxicity
      harbor mutations in the 12S rRNA gene, which can be detected by DNA screening.
      Also, the majority of these hearing losses could have been easily prevented by
      the simple taking of a clinical history. In these individuals, a genetic
      susceptibility to the ototoxic effects of aminoglycosides can be diagnosed, and
      deafness can be prevented in maternal relatives by avoidance of these
      antibiotics.

PMID- 9164620
TI  - Prediction of uvulopalatopharyngoplasty response using cephalometric radiographs.
AB  - PURPOSE: To evaluate the relationship between facial cephalometric measures and
      response to uvulopalatopharyngoplasty (UPPP). PATIENTS AND METHODS: Retrospective
      analysis of skeletal cephalometric measures obtained from a consecutive sample of
      43 patients with obstructive sleep apnea syndrome (OSAS) who underwent body mass
      index (BMI) measures, UPPP, upright lateral cephalometric radiographs, and
      preoperative and postoperative polysomnography. Significant clinical effect by
      uvulopalatopharyngoplasty was arbitrarily defined as having a 50% reduction in
      the respiratory disturbance index (RDI). The cephalometric measurements used were
      based solely on skeletal landmarks. RESULTS: No skeletal measurement predicted
      response to UPPP for the entire study population. When the patients were
      classified on the basis of retrognathia, 33 were identified without retrognathia.
      In that group, posterior airway length was the greatest predictor of response to
      UPPP (P < or = .05; odds ratio, 83.2). The distance between hyoid and mandible
      and the maxillary-mandibular relationship were also predictive of response (P <
      or = .05). CONCLUSION: The skeletal anatomy supporting the airway directly
      impacts the response to UPPP. Prediction of response requires stratification by
      skeletal subtype.

PMID- 9164621
TI  - The frequency of cricopharyngeal dysfunction on videofluoroscopic swallowing
      studies in patients with dysphagia.
AB  - PURPOSE: Dysphagia associated with cricopharyngeal dysfunction (CPD) is of
      particular interest to the otolaryngologist because it may respond to
      cricopharyngeal myotomy. There is a wide variation in the reported incidence of
      cricopharyngeal dysfunction in patients with dysphagia. This can be attributed to
      the different populations being studied, the lack of uniform criteria for
      diagnosis, and to different techniques used to evaluate patients. We have
      reviewed videofluoroscopic swallowing studies (VSS) conducted on 443 consecutive
      patients with complaints of dysphagia to identify the incidence of
      cricopharyngeal dysfunction. PATIENTS AND METHODS: The patient population
      consists of 443 veterans with complaints of dysphagia who were evaluated by
      videofluoroscopic swallowing studies at the Department of Veterans Affairs
      Medical Center, East Orange, NJ, between November 1988 and March 1993. RESULTS:
      Cricopharyngeal dysfunction was diagnosed radiologically as the appearance of a
      shelf in the posterior column of barium at the level of the cricoid cartilage. It
      was identified in 10 of 177 (5.7%) patients with neurological disorders, in 7 of
      142 (4.9%) patients with head and neck or esophageal tumors, and in 11 of 124
      (8.9%) patients with other medical problems. CONCLUSION: These results do not
      support the notion that cricopharyngeal dysfunction is an important factor in a
      significant proportion of patients with dysphagia. It is recognized that
      videofluoroscopy may not always detect cricopharyngeal dysfunction and that
      better criteria for identifying this entity are needed.

PMID- 9164622
TI  - Prognostic significance of computed tomography in tumors of the oral cavity and
      oropharynx treated with neoadjuvant chemotherapy.
AB  - BACKGROUND: Despite its high response rate, the use of neoadjuvant chemotherapy
      remains controversial. Pretherapeutic identification of subgroups of patients who
      are likely to respond to chemotherapy is of the utmost importance. PURPOSE: In
      this study, we have attempted to determine the relationship between specific
      radiological parameters and the response to neoadjuvant chemotherapy. In
      addition, we have determined if these parameters could yield prognostic
      information on recurrence and/or survival. PATIENTS AND METHODS: Fifty-four
      patients with a squamous cell carcinoma of the oral cavity or base of tongue who
      had had a contrast-enhanced CT scan and neoadjuvant chemotherapy were included in
      this analysis. All clinical, radiological, surgical, histological, and
      radiotherapeutical parameters as well as the follow-up data were analyzed by a
      chi-square test. The method of Kaplan-Meyer was used to determine disease-free
      intervals and crude survival. The log-rank method was used for testing
      differences in local failures and survival. RESULTS: Twenty-eight patients were
      classified as having isodense nodes and 20 patients as having hypodense nodes.
      Nodal density was not related to tumor size or primary site. N stage was not
      correlated with the density of the nodes. Patients with hypodense nodes had a
      significantly lower disease-free interval and survival than patients with
      isodense nodes. The relation between overall response to chemotherapy and the
      hypodensity of the nodes didn't reach a significant level. CONCLUSION: No
      relation was found between overall response to chemotherapy and N-stage or tumor
      density. Disease-free interval and crude survival was strongly related to
      response to chemotherapy.

PMID- 9164623
TI  - Accessory nerve damages and impaired shoulder movements after neck dissections.
AB  - PURPOSE: After neck dissection, where the accessory nerve is often excised
      patients usually complain of impaired shoulder movements. The accessory nerve
      forms a plexus with branches of the cervical nerves C2, C3, and C4. In the
      present study, the accessory nerve was examined during neck dissections to
      clarify the incidence of motor fibers in joining branches, and the function of
      the motor fibers was evaluated postoperatively in relation to shoulder movements.
      MATERIALS AND METHODS: Presence of cervical contributions to the accessory nerve
      were examined in 20 neck sides in 15 patients. Postoperative function of the
      shoulder movements was evaluated by manual muscle testing (MMT) and
      electromyography (EMG). RESULTS: Motor fibers in cervical contributions were
      noted on four sides (20%) by stimulation of joining branches. When the accessory
      nerve was excised, scapular elevation was rarely impaired even if there were no
      motor fibers in the cervical contributions. Excision of the accessory nerve
      caused poor scapular adduction and impaired scapular depression and adduction in
      most cases even if motor fibers in the cervical contributions existed.
      CONCLUSION: Postoperative impairment of scapular movements was not attributed to
      the presence or absence of motor fibers in joining branches. Results obtained
      with electromyography did not represent the practical function of the muscle.

PMID- 9164624
TI  - Diagnostic problems of tuberculous cervical adenitis (scrofula).
AB  - PURPOSE: This study was designed to review the diagnostic procedure for
      tuberculous cervical adenitis and propose a simple protocol for the work-up of
      patients with suspected tuberculous cervical adenitis. Moreover, it served to
      increase physician awareness of tuberculosis as possible cause of cervical mass.
      PATIENTS AND METHODS: We performed a retrospective study of 57 patients with
      tuberculous cervical adenitis who were treated at North West Armed Forces
      Hospital, Tabuk, Saudi Arabia between March 1989 and April 1993. The results of
      diagnostic procedures, chest x-ray, tuberculin test, fine-needle aspiration,
      microbiology culture, and histopathology were reviewed. RESULTS: Forteen percent
      showed changes in chest x-ray, 92% had positive tuberculin test, and 50% of the
      culture material grew Mycobacterium tuberculosis. All specimens for
      histopathology were suggestive of tuberculosis. CONCLUSION: A thorough history
      and physical examination, tuberculin test, and fine-needle aspiration will help
      arrive at an early diagnosis of tuberculous cervical adenitis and allow early
      commencement of treatment before final diagnosis can be made by incisional biopsy
      and culture. Tuberculosis should be included in the differential diagnosis of
      neck mass.

PMID- 9164625
TI  - Osteogenic sarcoma of the maxilla: preoperative magnetic resonance imaging and
      computed tomography analyses.

PMID- 9164626
TI  - Rapid magnetic resonance imaging for assessment of velopharyngeal muscle movement
      on phonation.

PMID- 9164627
TI  - Sutton's disease.

PMID- 9164628
TI  - Metastasis of squamous cell carcinoma of the conjunctiva: case report and review
      of the literature.

PMID- 9164629
TI  - Osteogenic sarcoma of the temporal bone.

PMID- 9164630
TI  - Epiglottitis diagnosed within hours of birth.

PMID- 9164631
TI  - Laryngotracheal stenosis in a case of Pena-Shokier syndrome.

PMID- 9164632
TI  - Spontaneous or interferon-gamma-induced T-cell infiltration, HLA-DR and ICAM-1
      expression in genitoanal warts are associated with TH1 or mixed TH1/TH2 cytokine
      mRNA expression profiles.
AB  - The purpose of the study was to investigate the cytokine gene expression patterns
      and immunohistochemical characteristics of genitoanal warts in order to obtain a
      clue as to the immunological mechanisms possibly relevant for wart regression or
      persistence. We analysed surgically removed warts from 11 patients, 2 of whom
      were immunosuppressed. Lesions of five of the nine otherwise healthy individuals
      were additionally treated with intralesional interferon-gamma (IFN gamma) prior
      to surgery. Invasion of CD4+ T cells into the papillomas and HLA-DR and ICAM-1
      expression on keratinocytes were found in two otherwise healthy patients and were
      intensified by intralesional IFN gamma in four of five patients. The mRNA
      expression patterns in seven of eight non-recurrent warts were compatible with a
      predominant TH1 or mixed TH1/TH2 cytokine profile. In contrast, in recalcitrant
      warts of three patients (one healthy, two immunocompromised) histological signs
      of immunore-activity and TH1-like cytokine mRNA expression were not detected. In
      recurrent warts of a renal transplant patient, IL-4 and IL-5 mRNA expression was
      repeatedly found suggesting a predominant TH2 response. In conclusion,
      immunoreactivity to genitoanal warts such as T-cell infiltration, HLA-DR and ICAM
      1 expression was associated with a predominant TH1 or mixed TH1/ TH2 cytokine
      mRNA expression profile.

PMID- 9164634
TI  - Mast cells and atopic dermatitis. Stereological quantification of mast cells in
      atopic dermatitis and normal human skin.
AB  - Stereological quantification of mast cell numbers was applied to sections of
      punch biopsies from lesional and nonlesional skin of atopic dermatitis patients
      and skin of healthy volunteers. We also investigated whether the method of
      staining and/or the fixative influenced the results of the determination of the
      mast cell profile numbers. The punch biopsies were taken from the same four
      locations in both atopic dermatitis patients and normal individuals. The
      locations were the scalp, neck and flexure of the elbow (lesional skin), and
      nates (nonlesional skin). Clinical scoring was carried out at the site of each
      biopsy. After fixation and plastic embedding, the biopsies were cut into 2
      microns serial sections. Ten sections, 30 microns apart, from each biopsy were
      examined and stained alternately with either toluidine blue or Giemsa stain and
      mast cell profile numbers were determined. The study yielded the following
      results: (1) in atopic dermatitis lesional skin an increased number of mast cell
      profiles was found as compared with nonlesional skin, (2) comparing atopic
      dermatitis skin with normal skin, a significantly increased number of mast cell
      profiles per millimetre squared was found in specimens from the neck, (3)
      staining with toluidine blue yielded a lower number of mast cell profiles than
      Giemsa staining, (4) the use of Carnoy's fixative resulted in a lower mast cell
      profile count than the use of formaldehyde, and (5) there was no statistically
      significant correlation between the clinical score and the number of mast cell
      profiles per millimetre squared. Using stereological techniques, this study
      indicated that mast cells might participate in the inflammatory process in skin
      leading to atopic dermatitis.

PMID- 9164633
TI  - sICAM-1, sE-selectin and sVCAM-1 are constitutively present in human skin lymph
      and increased in allergic contact dermatitis.
AB  - The expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell
      adhesion molecule-1 (VCAM-1) and E-selectin is important for the regulation of
      the leucocyte traffic into and in inflammatory dermatoses. ICAM-1, VCAM-1 and E
      selectin were initially identified as cell-surface proteins, but recent evidence
      suggests that they also exist in a soluble form. The collection of human afferent
      lymph exclusively deriving from a selected skin area allows insight into local
      pathomechanisms as well as signal transmission in skin disorders. In the present
      study we measured the concentrations of the soluble adhesion molecules (sAM)
      sICAM-1, sVCAM-1 and sE-selectin in human skin lymph derived from normal
      untreated skin, irritant contact dermatitis (CD) and the induction and
      elicitation phases of allergic CD. The strong elicitation reactions of allergic
      CD produced an increase in sAM output to about three times the baseline values
      but in the weaker irritant CD we observed no increase at all. In the induction
      phase of allergic CD the concentrations during the first 9 days of the experiment
      remained unchanged, as in the lymph derived from normal untreated skin, but were
      slightly increased thereafter. To our knowledge, no in vivo data exist on the
      local involvement of sAM in irritant and allergic CD in humans. Our results
      provide evidence of increased concentrations of sAM mainly in strong allergic CD.

PMID- 9164635
TI  - Functional studies of skin mast cells in lichen planus.
AB  - In order to identify possible functional differences between mast cells obtained
      from the skin of lichen planus (LP) patients and healthy donors, biopsies from
      lesional skin of 11 lichen planus patients and from normal skin of 7 healthy
      donors were sampled. Mast cells were obtained from the skin using an enzymatic
      dispersion technique. The cells were challenged in vitro with substance P (SP),
      tumor necrosis factor alpha (TNF-alpha) and anti-IgE. Their reactivity was
      estimated on the basis of histamine release. LP skin mast cells and healthy skin
      mast cells showed similar sensitivity to stimulation with TNF-alpha at a
      concentration of 10(-7) M (15.2% histamine release, as a proportion of total
      cellular content vs 15.9%) and to stimulation with anti-IgE at a dilution of
      1:100) (38.8% vs 37.0%). Spontaneous histamine release was also very similar in
      both the populations of mast cells (10.2% vs 12.7%, respectively). However, LP
      skin mast cells showed significantly higher (P < 0.01) sensitivity towards
      stimulation with SP at a concentration of 10(-4) M than healthy skin mast cells
      (15.9% histamine release vs 7.0%). This finding could suggest that neurogenic
      inflammatory mechanisms contribute to the pathogenesis of LP.

PMID- 9164636
TI  - Enkephalin-like immunoreactivity in human skin is found selectively in a fraction
      of CD68-positive dermal cells: increase in enkephalin-positive cells in lesional
      psoriasis.
AB  - Opioid peptides are synthesized in neurons, endocrine cells,
      monocytes/macrophages and B and T lymphocytes. They interact with opioid
      receptors located on immune cells and nociceptive nerve terminals. Because opioid
      peptides might be of importance in inflammatory skin diseases, for example
      psoriasis, sections of skin from psoriatic patients were immunohistochemically
      stained with antisera against methionine and leucine enkephalin, CD68 (KP1, PG
      M1), calprotectin (M747), M130 (Ber-MAC3), CD1a and CD3. Enkephalin-like activity
      was detected selectively in dermal CD68-positive macrophages/monocytes. The
      activity showed no association with the activation markers M747 and Ber-MAC3.
      There was a statistically significant increase in enkephalin-positive cells in
      involved psoriatic skin compared with uninvolved and normal skin. These results
      were confirmed by radioimmunoassay which showed elevated levels in extracts from
      involved psoriatic skin compared with uninvolved skin (81%) and normal skin
      (204%). Furthermore, preproenkephalin mRNA of an expected size was detected in
      involved psoriatic skin. If the increased levels of enkephalins present in
      monocytes/macrophages in psoriatic skin lesions reach the threshold for
      biological activity, they may play a role in the regulation of the inflammatory
      processes seen in this skin disease.

PMID- 9164637
TI  - Interdependence between degree of porphyrin excess and disease severity in
      congenital erythropoietic porphyria (Gunther's disease).
AB  - Various clinical and biochemical observations point to a relationship between
      degree of disease expression and metabolic disturbance in autosomal recessive
      congenital erythropoietic porphyria (Gunther's disease). Although the clinical
      manifestations have been well described since Gunther's fundamental observations,
      an interdependence between disease severity and porphyrin excess has yet to be
      elucidated. We investigated porphyrin metabolism in nine Indian patients
      suffering from the characteristic clinical symptoms: skin photosensitivity, red
      colored urine as a sign of extremely elevated porphyrinuria and mild to severe
      hemolytic anemia. Porphyrins in urine, feces and blood were analysed by HPTLC and
      HPLC in conjunction with spectrophotometry and spectrofluorometry.
      Uroporphyrinogen III synthase activities in red blood cells were determined using
      a coupled-enzyme assay. Biochemical studies revealed varying degrees of
      porphyrinuria with total urinary porphyrins between 23 and 102 mumol/24 h (normal
      < 0.2 mumol/24 h) and uroporphyrin predominance. Urinary and fecal coproporphyrin
      isomer I were markedly elevated to 87-97% and 81-93% (normal < 31%, < 75%),
      respectively. Overproduction of porphyrins led to a considerable porphyrinemia
      with mainly copro- and protoporphyrin. A hitherto undescribed fecal porphyrin
      pattern with increased protoporphyrin levels was found in three patients. This
      atypical finding was probably related to severe hemolysis since protoporphyrin
      can be excreted only via the liver with bile in the feces. High porphyrin levels
      in urine, feces and blood were associated with worse cutaneous symptoms.
      Activities of uroporphyrinogen III synthase in red blood cell lysates were
      decreased to between 9% and 30% of controls. Patients showed increased
      porphobilinogen deaminase activities, up to 190% of control. Deficiency of
      uroporphyrinogen III synthase activity was reflected by inversion of the
      relationship between and isomer III leading to dominance of isomer I. Elevation
      of porphobilinogen deaminase activities is related to hemolysis and,
      additionally, to regulatory compensation for the enzyme deficiency. Variations in
      both the severity of photosensitivity and the enhancement of porphyrin production
      and excretion indicate the molecular heterogeneity of this disease. These
      findings suggest a close relationship between the metabolic disturbance reflected
      by porphyrin excess and the severity of disease expression.

PMID- 9164638
TI  - Interleukin 1 beta and the stimulation of Langerhans cell migration: comparisons
      with tumour necrosis factor alpha.
AB  - Epidermal Langerhans cells (LC) and the cells into which they mature are believed
      to play a pivotal role in cutaneous immune function. The induction phase of
      contact sensitization is associated with the migration of LC from the skin and
      their accumulation as dendritic cells (DC) in lymph nodes draining the site of
      exposure. We have demonstrated previously that tumour necrosis factor alpha (TNF
      alpha), an epidermal cytokine produced by keratinocytes, provides one signal for
      LC migration. We describe here experiments designed to evaluate the influence of
      interleukin 1 beta (IL-1 beta), a product exclusively of LC in murine epidermis,
      on LC migration, LC morphology and DC accumulation, and to compare the effects of
      this cytokine with those of TNF-alpha. Both cytokines induced a significant
      reduction in the frequency of epidermal LC and the arrival of DC in draining
      lymph nodes. Changes in both parameters were induced more rapidly following
      intradermal administration of TNF-alpha than were observed after treatment with
      IL-1 beta. However, the reduction in LC frequency was more persistent with IL-1
      beta. Both cytokines caused the activation of LC, characterized by the
      acquisition of a more dendritic morphology and the increased expression of Ia
      molecules. These results demonstrate that IL-1 beta and TNF-alpha can each
      stimulate the migration of epidermal LC, but that the changes induced by these
      cytokines are not identical.

PMID- 9164639
TI  - Binding and in vitro modulation of human epidermal Langerhans cell functions by
      substance P.
AB  - Substance P (SP) is distributed in both the central and peripheral nervous
      system. It has various effects on immunocompetent cells, such as macrophages and
      lymphocytes. The aim of our study was to search for the presence of SP receptors
      (SP-R) on human cutaneous Langerhans cells (LC), and to determine the effects of
      SP on LC immunological functions in a model of mixed epidermal cell-lymphocyte
      reaction (MELR). Radioligand binding studies showed that LC-enriched epidermal
      cell suspensions reversibly bound SP, and that the specific binding increased
      with the percentage of LC. Functional assays showed that SP had no effect when
      added at concentrations from 10(-6) M to 10(-12) M to the MELR. The addition of
      SP at concentrations of 10(-4) M and 10(-5) M was able to inhibit the allogeneic
      T-cell response (98.3 +/- 1.8% and 92.8 +/- 8.9% inhibition, respectively)
      without modifying the cell viability. This inhibition was through an effect of SP
      on both T-cell and LC function. We conclude that SP has receptors on LC and may
      inhibit antigen presentation.

PMID- 9164640
TI  - A simple immunofluorescence technique for simultaneous visualization of mast
      cells and nerve fibers reveals selectivity and hair cycle--dependent changes in
      mast cell--nerve fiber contacts in murine skin.
AB  - Close contacts between mast cells (MC) and nerve fibers have previously been
      demonstrated in normal and inflamed skin by light and electron microscopy. A key
      step for any study in MC-nerve interactions in situ is to simultaneously
      visualize both communication partners, preferably with the option of double
      labelling the nerve fibers. For this purpose, we developed the following triple
      staining technique. After paraformaldehyde-picric acid perfusion fixation,
      cryostat sections of back skin from C57BL/6 mice were incubated with a primary
      rat monoclonal antibody to substance P (SP), followed by incubation with a
      secondary goat-anti-rat TRITC-conjugated IgG. A rabbit antiserum to CGRP was then
      applied, followed by a secondary goat-anti-rabbit FITC-conjugated IgG. MCs were
      visualized by incubation with AMCA-labelled avidin, or (for a more convenient
      quantification of close MC-nerve fiber contacts) with a mixture of TRITC- and
      FITC-labelled avidins. Using this simple, novel covisualization method, we were
      able to show that MC-nerve associations in mouse skin are, contrary to previous
      suggestions, highly selective for nerve fiber types, and that these interactions
      are regulated in a hair cycle-dependent manner: in telogen and early anagen skin,
      MCs preferentially contacted CGRP-immunoreactive (IR) or SP/CGRP-IR double
      labelled nerve fibers. Compared with telogen values, there was a significant
      increase in the number of close contacts between MCs and tyrosine hydroxylase-IR
      fibers during late anagen, and between MCs and peptide histidine-methionine-IR
      and choline acetyl transferase-IR fibers during catagen.

PMID- 9164641
TI  - Missense mutation in exon 2 of alpha-galactosidase A in a patient with Fabry
      disease.

PMID- 9164642
TI  - Blistering skin diseases: models for studies on epidermal-dermal adhesion.
AB  - Blistering skin diseases represent a genetically and biologically heterogeneous
      group of pathologic conditions with attenuated epithelial adhesion in the skin or
      in mucosal surfaces. Investigations on genetic blistering disorders with
      ultrastructural analysis, determination of candidate genes, and isolation and
      characterization of the target proteins have had a major impact on our
      understanding of normal epithelial-mesenchymal interactions and epithelial cell
      adhesion in general. A higf1p4gree of molecular heterogeneity underlies the
      different pathological phenotypes, and certain genotype-phenotype correlations
      are starting to emerge. Accumulating data on the molecular basis of different
      blistering diseases have already disclosed ample new information on the
      physiological functions of many of the molecular components of the dermal
      epidermal junction, and we expect a rapid expansion of knowledge on the field
      when genotype-phenotype correlations of more patients are discerned.

PMID- 9164643
TI  - Regulation of extracellular matrix synthesis by mechanical stress.
AB  - The extracellular matrix (ECM) provides mechanical support to tissues and is a
      substrate for cell adhesion and differentiation. Cells bind to ECM via specific
      cell surface receptors such as integrins. When engaging with ECM ligands, these
      receptors can activate signal transduction pathways within the cells and may act
      as mechanochemical transducers. Thus, interaction of cells with ECM can modulate
      gene expression although the exact mechanisms are not known. Among the genes that
      are, in part, controlled by cell-ECM interactions are those for certain ECM
      components themselves. Bone cells, for example, remodel their matrix and reorient
      bone trabeculae in response to mechanical strain. Recently, we found that
      fibroblasts attached to a strained collagen matrix produce more of the ECM
      glycoproteins tenascin and collagen XII than cells in a relaxed matrix. In vivo,
      these two proteins are specifically expressed in places where mechanical strain
      is high. We also showed that the chick tenascin gene promoter contains a novel
      cis-acting, "strain-responsive" element that causes enhanced transcription in
      cells attached to a strained collagen matrix. Similar enhancer elements might be
      present in the promoters of other genes induced by mechanical stress. It can be
      speculated that connective tissue cells sense force vectors in their ECM
      environment and react to altered mechanical needs by regulating the transcription
      of specific ECM genes; this process is a prerequisite for matrix remodeling.

PMID- 9164644
TI  - Novel self-association fibronectin sites.
AB  - In this study, we report a strong interaction between two contiguous proteolytic
      fragments of fibronectin, each having a mass of about 16 kDa. This interaction
      was stable in 4 M NaCl and 4 M urea and dissociation of the two fragments
      required buffers containing 0.5% sodium dodecyl sulphate. After purification,
      these peptides maintained their ability to interact when mixed. One fragment was
      made up of type III repeat 4 and part of 5, the other by repeat 6 and part of 5.
      Such strong interaction between two fibronectin regions may play a role in
      fibronectin conformation as well as during fibronectin fibril formation.

PMID- 9164645
TI  - The roles of adhesion molecules and proteinases in lymphocyte transendothelial
      migration.
AB  - T cell extravasation into perivascular tissue during inflammation involves
      transmigration through the endothelial cell (EC) layer and basement membrane. We
      have demonstrated that matrix metalloxproteinase-2 (MMP-2) is induced in T cells
      upon adhesion to endothelial cells and that the induction of MMP-2 is mediated by
      binding of T cell VLA-4 to VCAM-1. Cloned murine Th1 cells antigenic to myelin
      basic protein, either expressing VLA-4 on their cell surface and causing
      experimental autoimmune encephalomyelitis (EAE) or not expressing VLA-4 and not
      causing EAE, were used. VLA-4 positive (+) T cells that adhered to VCAM-1
      positive (+) endothelial cells exhibited an induction in MMP-2 mRNA, protein, and
      activity, whereas MMP-2 was not induced in the T cells that adhered to the VCAM-1
      negative (-) endothelial cells or VLA-4 negative (-) T cells that adhered to VCAM
      1+ endothelial cells. Incubating T cells with rVCAM-1-coated dishes showed that
      VLA-4+ T cells adhered to the molecule and that adhesion to rVCAM-1 was
      sufficient to induce MMP-2. VLA-4+ T cells that had transmigrated through a VCAM
      1+ endothelial cell monolayer exhibited MMP-2 activity. TIMP-2 was shown to
      reduce T cell transmigration in vitro. Transmigrated T cells exhibited
      downregulation of VLA-4 and LFA-1 integrin surface expression and decreased
      binding to rVCAM-1 and rICAM-1 and increased binding to collagens I and IV,
      fibronectin, and laminin. Brain sections of mice demonstrated that as T cells
      migrated farther into the tissue, VLA-4 expression was lost, although CD4
      expression remained unchanged. These results demonstrate that binding to VCAM-1
      on endothelial cells induces MMP-2 in T cells, which, in turn, may facilitate T
      cell migration into perivascular tissue. The significance of these findings in
      the modulation of the inflammatory response is discussed.

PMID- 9164646
TI  - Collagenase: a key enzyme in collagen turnover.
AB  - The primary agents responsible for cartilage and bone destruction in joint
      diseases are active proteinases that degrade collagen and proteoglycan. All four
      main classes of proteolytic enzymes are involved in either the normal turnover of
      connective tissue or its pathological destruction. These proteinases are made by
      different cells found within the joints. Both extracellular and intracellular
      pathways exist and individual enzymes can be inhibited by specific proteinaceous
      inhibitors that block their activity. Recent research has implicated the matrix
      metalloproteinases (MMPs) in many of the processes involved in joint diseases.
      The metalloproteinases are capable of degrading all components of the
      extracellular matrix. This family of proteinases contains a group of at least
      three collagenases that are capable of degrading native fibrillar collagen.
      Collagen degradation within joint disease is recognized as the irreversible step
      in the destruction of cartilage that leads to a failure in joint function. The
      collagenases are the enzymes necessary to initiate collagen turnover in normal
      connective tissue turnover and in disease.

PMID- 9164647
TI  - Regulation of matrilysin in the rat uterus.
AB  - Matrilysin was first discovered in the involuting rat uterus; it has also been
      known as uterine metalloproteinase, putative metalloproteinase (Pump-1), and
      matrix metalloproteinase 7 (MMP-7). It is the smallest member (28 kDa) of a
      family of 15 MMPs that together are able to degrade most of the macromolecules of
      the extracellular matrix. This family is briefly reviewed; all members are zinc
      metalloproteinases that occur in zymogen form with the active site zinc blocked
      by cysteine. Matrilysin can degrade a wide range of gelatins, proteoglycans, and
      glycoproteins of the matrix and can activate several other MMPs including
      collagenase. With respect to the uterus, matrilysin is localized to epithelial
      cells and varies in amount with the estrus cycle and is found in high levels
      during postpartum involution. There is evidence for a role in the last stage of
      cervical ripening and immediately postpartum. Induction of premature delivery by
      onapristone and prostaglandin E2 advances these changes in matrilysin. Regulation
      of the enzyme levels in the uterus are considered from four viewpoints: control
      of protein synthesis (particularly in response to hormones), activation of the
      proenzyme to functional protease, retention of enzyme by binding to matrix
      components such as heparan sulfate, and inhibition by natural inhibitors such as
      tissue inhibitor of metalloproteinases (TIMPs) and alpha 2-macroglobulin.

PMID- 9164648
TI  - Ligand binding and affinity modulation of integrins.
AB  - Integrins are cell adhesion receptors that mediate cell-cell and cell
      extracellular matrix interactions. The extracellular domains of these receptors
      possess binding sites for a diverse range of protein ligands. Ligand binding is
      divalent cation dependent and involves well-defined motifs in the ligand.
      Integrins can dynamically regulate their affinity for ligands (inside-out
      signaling). This ability to rapidly modulate their affinity state is key to their
      involvement in such processes as cell migration and platelet aggregation. This
      review will focus on two aspects of integrin function: first, on the molecular
      basis of ligand-integrin interactions and, second, on the underlying mechanisms
      controlling the affinity state of integrins for their ligands.

PMID- 9164649
TI  - Tumor progression and angiogenesis: cathepsin B & Co.
AB  - Experimental and clinical evidence reveals that the growth of solid tumors is
      dependent on angiogenesis. Proteolytic enzymes such as plasminogen activators and
      matrix metalloproteinases have been implicated in this neovascularization. The
      role of lysosomal proteases in this process has yet to be explored. Increased
      expression of the lysosomal cysteine protease cathepsin B has been observed in
      many etiologically different tumors, including human brain, prostate, breast, and
      gastrointestinal cancers. Immunohistochemical and in situ histochemical studies
      have demonstrated expression of cathepsin B in neovessels induced during
      malignant progression of human glioblastoma and prostate carcinomas. In these two
      tumor types, neovessels stain strongly for cathepsin B compared with the normal
      microvasculature. As an initial point to elucidate whether cathepsin B is an
      important component of the angiogenic response in tumours, we analyzed expression
      of cathepsin B in endothelial cells during neovessel formation. We present
      evidence for strong immunostaining of cathepsin B in rat brain microvascular
      endothelial cells as they form capillary tubes in vitro. This finding is
      discussed within the general framework of the role of proteolytic enzymes in
      tumor invasion and angiogenesis.

PMID- 9164650
TI  - The integrin alpha 6 beta 4 and the biology of carcinoma.
AB  - The integrin family of adhesion receptors plays a major role in epithelial
      organization and function. Moreover, the altered expression and function of
      specific integrins most likely contributes significantly to carcinoma
      progression. The integrin alpha 6 beta 4, the focus of this review, is a receptor
      for several members of the laminin family and is preferentially expressed at the
      basal surface of most epithelia, where it contributes to basement membrane
      interactions. Mounting evidence suggests that the alpha 6 beta 4 integrin plays a
      key role in carcinoma cell biology. Several histopathological studies have
      established a correlation between alpha 6 beta 4 integrin expression and tumor
      progression. The importance of alpha 6 beta 4 expression in tumors in underscored
      by the findings that invading fronts of several carcinomas are enriched in the
      expression of alpha 6 beta 4 integrin ligands, such as laminin-1 and laminin-5.
      The participation of the alpha 6 beta 4 integrin in invasion is supported further
      by in vitro functional studies using carcinoma cells that have been transfected
      with the beta 4 cDNA. The mechanisms by which alpha 6 beta 4 contributes to tumor
      progression are probably related to its mechanical and signaling properties and
      are currently under intense study.

PMID- 9164651
TI  - Molecular regulation of cellular invasion--role of gelatinase A and TIMP-2.
AB  - Extracellular matrix (ECM) turnover is an event that is tightly regulated. Much
      of the coordinate (physiological) or discoordinate (pathological) degradation of
      the ECM is catalyzed by a class of proteases known as the matrix
      metalloproteinases (MMPs) or matrixins. Matrixins are a family of homologous Zn
      atom dependent endopeptidases that are usually secreted from cells as inactive
      zymogens. Net degradative activity in the extracellular environment is regulated
      by specific activators and inhibitors. One member of the matrixin family,
      gelatinase A, is regulated differently from other MMPs, suggesting that it may
      play a unique role in cell-matrix interactions, including cell invasion. The
      conversion from the 72 kDa progelatinase A to the active 62 kDa species may be a
      key event in the acquisition of invasive potential. This discussion reviews some
      recent findings on the cellular mechanisms involved in progelatinase A activation
      and, in particular, the role of tissue inhibitor of matrix metalloproteinases-2
      (TIMP-2) and transmembrane containing metalloproteinases (MT-MMP) in this
      process.

PMID- 9164654
TI  - Different human tenascin-C variants in the extracellular matrix of cultured human
      fibroblasts.
AB  - Using an immunoadsorbent prepared with a monoclonal antibody specific for the
      high molecular mass isoform of human tenascin-C, we purified tenascin-C molecules
      containing at least one large subunit from the extracellular matrix of cultured
      normal human fibroblasts. Sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis and immunoblotting analyses have shown that both high and low
      molecular mass subunits are present in these tenascin-C preparations. Because the
      monoclonal antibody used is able to bind only the high molecular mass isoform,
      the present data show that part of the tenascin-C present in the fibroblast
      extracellular matrix is made up of heterohexameric molecules.

PMID- 9164653
TI  - A review of tissue inhibitor of metalloproteinases-3 (TIMP-3) and experimental
      analysis of its effect on primary tumor growth.
AB  - The family of tissue inhibitors of metalloproteinases (TIMPs) presently numbers
      four distinct gene products that are specific inhibitors of the matrix
      metalloproteinases (MMPs). The local balance between MMPs and TIMPs is believed
      to play a major role in extracellular matrix (ECM) remodeling during development
      and in diseases such as cancer and arthritis. Unlike the other TIMPs, which are
      soluble. TIMP-3 is unique in being a component of ECM. Mutations in the human
      TIMP-3 gene cause a dominantly inherited, adult-onset blindness (Sorsby's fundus
      dystrophy or SFD). In this article, we summarize what is currently known about
      TIMP-3, discuss possible mechanisms leading up to SFD, and investigate the effect
      of TIMP-3 on tumor growth. Breast carcinoma and malignant melanoma cell lines
      were transfected with TIMP-3 expression plasmids and injected subcutaneously into
      nude mice. Growth curves of the resulting tumors over a period of 6 to 8 weeks
      demonstrated that increased expression of TIMP-3 resulted in a statistically
      significant suppression of tumor growth. Deposition of TIMP-3 in the surrounding
      ECM by tumor cells may inhibit tumor growth by preventing local expansion of
      tumor, retarding the release of growth factors sequestered in ECM, or inhibiting
      angiogenesis. TIMP-3 over-expression had no effect on the growth of the two tumor
      cell lines in vitro. Because recombinant TIMP-3 inhibits endothelial cell
      migration and tube formation in response to angiogenic factors, we believe that
      the effect of TIMP-3 on tumor growth seen in this study may be a consequence of
      its angiostatic action.

PMID- 9164655
TI  - Variants of integrin beta 4 subunit in human endometrial adenocarcinoma cells:
      mediators of ECM-induced differentiation?
AB  - The influence of extracellular matrix (ECM) on expression and function of
      integrins in carcinogenesis and differentiation is not well understood, but the
      importance of altered adhesion features for tumor development and progression is
      obvious. Integrins as versatile molecules are mainly responsible for mediating
      cell-matrix interactions and transmembrane signal transduction. They are capable
      of transducing outside-in signals from ECM components or conversely to organize
      the matrix by inside-out signaling. In the study presented here, we report that
      the reconstituted basement membrane, Matrigel, which induces morphological and
      functional differentiation of the endometrial adenocarcinoma cell line HEC 1B(L),
      also regulates the expression of various forms of the integrin beta 4 subunit.
      Furthermore, we were able to identify full-length isoforms with and without an
      altered cytoplasmic domain as well as truncated forms. Our findings suggest a
      regulatory role of integrin beta 4 isoforms and fragments in the process of in
      vitro differentiation of HEC 1B(L).

PMID- 9164656
TI  - Laminin mediates basement membrane induced differentiation of HEC 1B endometrial
      adenocarcinoma cells.
AB  - In vitro studies on endometrial carcinogenesis have been hampered by limited
      differentiation of the cells in culture. Using the endometrial carcinoma cell
      lines HEC 1B and its subclone HEC 1B(L), we established and characterized cell
      culture conditions that preserve a more differentiated state of the tumor cells.
      Randomly seeded HEC 1B(L) cells, if grown in a serum-free defined medium on top
      of a reconstituted basement membrane (Matrigel), within a few hours assembled
      themselves to web-like structures. In a thick layer of Matrigel, they showed an
      even more pronounced morphological differentiation. Functionally, two additional
      secretory proteins, about 31 and 77 kDa in size, became apparent as a response to
      matrigel. To further investigate the regulatory role of the extracellular matrix
      in the process of in vitro differentiation of endometrial adenocarcinoma cells,
      we addressed two specific problems. First, we investigated if the capacity of in
      vitro differentiation is a specific feature of HEC 1B(L) cells or if it is common
      to all endometrial adenocarcinoma cells. Second, we tried to identify the
      Matrigel component(s) responsible for in vitro differentiation. The assembly of
      HEC 1B and HEC 1B(L) cells into spatially organized web-like structures and the
      expression of the 77 kDa protein were thereby used as an assay. All endometrial
      adenocarcinoma cell lines tested to a variable degree formed web-like structures
      on Matrigel. Although the pattern of de novo synthesized secretory proteins
      changed as a response to Matrigel, only HEC 1A, HEC 1B, HEC 1B(L), and Ishikawa
      cells responded to culture on Matrigel by an increased expression of the 77 kDa
      protein. Functionally, polyclonal anti-laminin antibodies, but not anti-collagen
      type IV antibodies, disrupted formation of web-like structures by HEC 1B cells.
      The laminin-specific peptides YIGSR and SIKVAV but none of the RGD-peptides RGDS,
      GRGDSP, or GRADSP affected the three-dimensional assembly of these cells in
      vitro. Both anti-laminin antibodies and laminin-specific peptides suppressed
      Matrigel-induced formation of the 77-kDa secretory protein by HEC 1B cells. These
      findings suggest the involvement of laminin in the in vitro differentiation of
      the HEC 1B endometrial adenocarcinoma cell line. In a mechanistic view, laminin
      appears to play a crucial role in the regulation of this in vitro differentiation
      process.

PMID- 9164652
TI  - The importance of the microenvironment in breast cancer progression:
      recapitulation of mammary tumorigenesis using a unique human mammary epithelial
      cell model and a three-dimensional culture assay.
AB  - The extracellular matrix (ECM) is a dominant regulator of tissue development and
      homeostasis. "Designer microenvironments" in culture and in vivo model systems
      have shown that the ECM regulates growth, differentiation, and apoptosis in
      murine and human mammary epithelial cells (MEC) through a hierarchy of
      transcriptional events involving the intricate interplay between soluble and
      physical signaling pathways. Furthermore, these studies have shown that these
      pathways direct and in turn are influenced by the tissue structure. Tissue
      structure is directed by the cooperative interactions of the cell-cell and cell
      ECM pathways and can be modified by stromal factors. Not surprisingly then, loss
      of tissue structure and alterations in ECM components are associated with the
      appearance and dissemination of breast tumors, and malignancy is associated with
      perturbations in cell adhesion, changes in adhesion molecules, and a stromal
      reaction. Several lines of evidence now support the contention that the
      pathogenesis of breast cancer is determined (at least in part) by the dynamic
      interplay between the ductal epithelial cells, the microenvironment, and the
      tissue structure (acini). Thus, to understand the mechanisms involved in
      carcinogenesis, the role of the microenvironment (ECM as well as the stromal
      cells) with respect to tissue structure should be considered and studied. Towards
      this goal, we have established a unique human MEC model of tumorigenesis, which
      in concert with a three-dimensional assay, recapitulates many of the genetic and
      morphological changes observed in breast in cancer in vivo. We are currently
      using this system to understand the role of the microenvironment and tissue
      structure in breast cancer progression.

PMID- 9164657
TI  - Heparan sulfate proteoglycans function in the binding and degradation of
      vitronectin by fibroblast monolayers.
AB  - Vitronectin, a 75-kDa plasma protein is also found in the extracellular matrix,
      where it is believed to promote cell adhesion and migration. In addition to its
      role in adhesion, matrix vitronectin is also believed to function as an opsonin
      promoting the clearance of thrombin-serpin complexes from the matrix. Vitronectin
      is cleared from the matrix by receptor-mediated endocytosis followed by lysosomal
      degradation, suggesting that cells can regulate the levels of vitronectin present
      in the matrix. However, the mechanism by which plasma vitronectin associates with
      the extracellular matrix remains unclear. Studies were conducted to define the
      binding site(s) for vitronectin in fibroblast cell layers. Sodium chlorate, a
      competitive inhibitor of proteoglycan sulfation, produced a dose-dependent
      decrease in both binding and degradation of vitronectin. This inhibition was
      reversible in that removal of chlorate returned both binding and degradation of
      vitronectin to near control levels within 24 h. The binding of vitronectin to
      cell layers was not dependent on cells because vitronectin bound directly to
      isolated matrix. Isolated matrices prepared from cell layers treated with sodium
      chlorate also exhibited a dose-dependent decrease in vitronectin binding,
      consistent with the binding site for vitronectin in the matrix being sulfated
      proteoglycans. Binding and degradation of vitronectin were also sensitive to the
      addition of exogenous heparin, suggesting that the heparin binding domain of
      vitronectin was mediating binding to the matrix. Incubating fibroblast monolayers
      with heparinase III resulted in a 40% decrease in binding and degradation of
      vitronectin. Taken together, the above findings suggest that vitronectin's
      binding to the matrix and its subsequent degradation are dependent on heparan
      sulfate proteoglycans.

PMID- 9164658
TI  - Localization of urokinase to focal adhesions by human fibrosarcoma cells
      synthesizing recombinant vitronectin.
AB  - Cell surface plasminogen activators have been proposed to participate in cell
      migration and invasion by activating both intracellular signaling pathways and
      extracellular proteolysis. Urokinase-type plasminogen activator (uPA) is secreted
      from many cell types and localizes to focal contact areas when cells are seeded
      onto the plasma protein vitronectin. Induction of vitronectin synthesis during
      migration of neural crest cells and growth of certain tumors suggests that the de
      novo synthesis and deposition of vitronectin into the tissue matrix may remodel
      the matrix to provide an environment suitable for cell migration and (or) tumor
      invasion. To investigate the effects of vitronectin secretion and matrix
      deposition on the localization and activity of cell-associated uPA, HT-1080
      fibrosarcoma cells were transfected with the Rc/CMV expression vector containing
      a vitronectin cDNA insert and stable cell lines expressing vitronectin were
      selected. Vitronectin-secreting cells were allowed to attach and spread on
      collagen- and fibronectin-coated substrates. Within 6 h, vitronectin was detected
      on the substrate; vitronectin synthesis was accompanied by the clustering of both
      the alpha v beta 5 vitronectin receptor and uPA into vinculin-containing focal
      adhesions. Although mock transfected cells formed small focal adhesions on both
      collagen and fibronectin, no co-localization of uPA or alpha v beta 5 to focal
      adhesions was evident in these cells. Vitronectin-secreting cells also exhibited
      decreased levels of plasminogen activation and increased levels of cell adhesion
      as compared with the mock transfected cells. These data demonstrate that the
      synthesis of vitronectin and its matrix association by transfected HT-1080
      fibrosarcoma cells results in localization of uPA to alpha v beta 5 containing
      focal adhesions, decreased cell surface uPA activity, and an increase in cell
      adhesion.

PMID- 9164659
TI  - An in vitro system for the study of matrix metalloproteases during
      decidualization in the mouse.
AB  - Decidualization results in the remodeling of the extracellular matrix with the
      loss of collagen type I and the appearance of basement membrane matrix
      components. We have developed an in vitro assay system to study matrix
      metalloproteases during mouse decidualization. Uterine stroma, or decidua
      isolated from day 7.5 pregnant mice, were grown on a three-dimensional collagen
      type I matrix (Vitrogen). Gelatin zymography of conditioned media from these
      cultures showed constitutive secretion of processed forms of gelatinase A at 65,
      62, and 59 kDa with 62 kDa predominating. Similar patterns of gelatinase A
      expression were obtained from tissue lysates of decidualizing uteri from days 5.5
      to 7.5 of development. Cells cultured on Vitrogen, but not on plastic or matrix
      coated dishes, were able to process the proenzyme to the 59 kDa form as observed
      in vivo. Only stroma cells cultured on a coating of collagen type I displayed the
      same increase in the 59 kDa zymogen. Decidua cells grown on Vitrogen attached and
      then migrated into aggregates that eventually penetrated the gel and spread as
      differentiated decidua on the underlying plastic. These preliminary results
      suggested that the in vitro assay system can be used to study the role of
      metalloproteases in matrix remodeling during decidualization.

PMID- 9164660
TI  - Mercury from maternal "silver" tooth fillings in sheep and human breast milk. A
      source of neonatal exposure.
AB  - Neonatal uptake of mercury (Hg) from milk was examined in a pregnant sheep model,
      where radioactive mercury (Hg203)/silver tooth fillings (amalgam) were newly
      placed. A crossover experimental design was used in which lactating ewes nursed
      foster lambs. In a parallel study, the relationship between dental history and
      breast milk concentration of Hg was also examined in 33 lactating women. Results
      from the animal studies showed that, during pregnancy, a primary fetal site of
      amalgam Hg concentration is the liver, and, after delivery, the neonatal lamb
      kidney receives additional amalgam Hg from mother's milk. In lactating women with
      aged amalgam fillings, increased Hg excretion in breast milk and urine correlated
      with the number of fillings or Hg vapor concentration levels in mouth air. It was
      concluded that Hg originating from maternal amalgam tooth fillings transfers
      across the placenta to the fetus, across the mammary gland into milk ingested by
      the newborn, and ultimately into neonatal body tissues. Comparisons are made to
      the U. S. minimal risk level recently established for adult Hg exposure. These
      findings suggest that placement and removal of "silver" tooth fillings in
      pregnant and lactating humans will subject the fetus and neonate to unnecessary
      risk of Hg exposure.

PMID- 9164661
TI  - Supplementation of calves with stabilized orthosilicic acid. Effect on the Si,
      Ca, Mg, and P concentrations in serum and the collagen concentration in skin and
      cartilage.
AB  - The bioavailability of silicon in stabilized orthosilicic acid was investigated
      in a double blind, placebo controlled supplementation study of calves maintained
      on a normal diet. The total dietary Si intake was increased by 4.9% in the form
      of stabilized orthosilicic acid. After 23 wk of Si supplementation, the serum Si
      concentration increased (p = 0.0001, n = 29) by 70% compared to control animals
      in spite of the low Si dose administered and the Si adequate diet. The
      individually administered Si dose was significantly associated with the serum Si
      concentration (r = 0.44, p = 0.016, n = 29). The collagen concentration in dermis
      was significantly higher (p = 0.019, n = 4) in the Si group and a positive
      correlation (r = 0.72, p = 0.018, n = 9) was found between the Si concentration
      in serum and the collagen concentration in cartilage. The calcium (Ca) and
      phosphorus (P) concentrations in serum were marginally higher for animals
      supplemented with Si compared to control animals. In serum, a significant linear
      relationship was found between the Si and the Ca concentration (r = 0.31, p =
      0.019, n = 59), whereas the magnesium concentration correlated marginally with
      the Si concentration (r = 0.25, p = 0.068, n = 59). In summary, increasing the
      total dietary Si intake by 4.9% in the form of stabilized orthosilicic acid
      resulted in a 70% higher Si concentration in serum indicating a high
      bioavailability of Si in this supplement. The positive correlation between the
      serum Si concentration and the collagen concentration in cartilage and the serum
      Ca concentration, respectively, suggest the involvement of Si both in the
      formation of extracellular matrix components and in Ca metabolism.

PMID- 9164662
TI  - Serum boron concentration from inhabitants of an urban area in Japan. Reference
      value and interval for the health screening of boron exposure.
AB  - Boron (B) levels were determined in the serum of 980 healthy inhabitants living
      in an urban area of Japan by means of inductively coupled plasma emission
      spectrometry (ICPES). The results showed a log-normal distribution of serum B for
      both sexes, although there are age-related differences. In male subjects, serum B
      increases rapidly up to 49 yr of age, reaching a plateau between ages 50 and 69
      yr old, followed by a gradual increase up to 70 yr or older. Female subjects
      exhibit a gradual increase up to the age of 70 yr old. The reference value for
      male and female subjects was 79.8 micrograms/L and 67.9 micrograms/L, and the
      reference interval was 33.3-191.2 micrograms/L and 29.5-154.9 micrograms/L,
      respectively. The obtained reference value and interval of the nonexposed group
      may be useful for health screening for B exposure, either for people living in
      regions with high levels of B in the environment, or for workers who are exposed
      to this element.

PMID- 9164663
TI  - Protective effect of magnesium supplementation on experimental 3-methyl
      cholanthrene-induced fibrosarcoma and changes in tissue magnesium distribution
      during carcinogenesis in rats.
AB  - In this study, we wanted to examine the effect of magnesium (Mg2+)
      supplementation on the experimental 3-methyl cholanthrene (3-MC)-induced
      fibrosarcoma and alterations in (Mg2+) distribution in several tissues of the
      rats, during carcinogenesis. It was determined that serum and tissue (Mg2+)
      levels of the rats in (Mg2+)-supplemented diet group were higher than those of
      the rats in the (Mg2+)-nonsupplemented and control groups. The mean time of
      fibrosarcoma development for (Mg2+)-supplemented group was longer than (Mg2+)
      nonsupplemented group (p < 0.05). Symptoms of hypermagnesemia were not observed
      in any of the rats. These results suggests that dietary (Mg2+) supplementation
      may have a partial anti-carcinogenic effect on experimental 3-MC-induced
      fibrosarcoma by prolongation of the latent period of carcinogenesis.

PMID- 9164664
TI  - Trace elements, age, and sex in amyotrophic lateral sclerosis disease.
AB  - The statistical tests analysis of variance, analysis of covariance, correlation
      coefficient, Kolmogorov-Smirnov test, t-test, and Tukey test were applied to
      copper, magnesium, manganese, and zinc content in serum (S) and in cerebrospinal
      fluid (CSF) of controls and of a sporadic form of Amyotrophic Lateral Sclerosis
      (ALS) disease. This is carried out in order to evaluate statistically the
      possible relationships among the trace elements when ALS patients and controls
      are considered as independent groups, within sex groups and within age decades of
      both patients and control classes. A statistically significant difference between
      older controls (age > 40) and ALS patients (age > 40) for copper in CSF, copper
      in S, manganese in S, and zinc in CSF was found. Statistically significant
      correlation coefficients within the different classes formed for this study were
      observed. Within this pool, a correlation of patient group can differ
      statistically from the corresponding one of controls and vice versa. Thus, this
      correlation could be characteristic of the group from which is extracted, e.g.,
      the correlation between copper in S and zinc in S, which is characteristic of ALS
      patients when considered as an independent group as well as members of the male
      patient class.

PMID- 9164665
TI  - Studies on the effects of selenium on rumen microbial fermentation in vitro.
AB  - The effects of selenium (Se) on ruminant microbial fermentation were investigated
      in vitro using rumen microflora collected from a rumen-fistulated dairy cow.
      First, the effects of L-selenomethionine (SeMet; at 0.2 or 2 ppm Se) in the
      presence or absence of wheat bran (WB, 500 mg per incubation flask) were
      evaluated. Second, the effects of several forms of Se (elemental Se: 50 ppm Se;
      sodium selenite: 2 ppm Se; SeMet: 2 ppm Se) were compared. Results showed that
      the amounts of short-chain fatty acids (SCFAs) tended to be increased by SeMet
      treatment, whereas SeMet in the presence of WB transiently suppressed
      fermentation. The addition of SeMet tended to increase the production of acetate
      while reducing the production of butyrate with the without WB supplementation.
      Among the different Se compounds tested, the amounts of SCFAs were greater with
      SeMet treatment, which yielded a higher proportion of acetate compared to other
      treatments. Selenite did not influence the total SCFAs concentrations; however,
      it increased the relative proportion of butyrate at the expense of acetate.
      Elemental Se did not significantly affect fermentation. Higher bacterial Se
      concentrations were observed for selenite than for SeMet. It was concluded that
      Se supplementation can influence rumen microbial fermentation and that Se
      compounds differ in this regard.

PMID- 9164666
TI  - Effects of selenium on colonic fermentation in the rat.
AB  - Studies were conducted to determine the effects of dietary selenium (Se) on the
      hindgut microbial activity in rats. Selenium was fed as L-selenomethionine
      (SeMet) at either 0 or 2 ppm Se in the presence or absence of wheat bran (WB,
      10%), a known substrate for the enteric microflora. Wheat bran feeding caused the
      greatest fermentation, measured by the production of short-chain fatty acids
      (SCFAs) along the entire intestinal tract and feces; however, its effects were
      suppressed by SeMet in the proximal large bowel, cecum, and colon. Selenium
      significantly enhanced fermentation in the colon and rectum, but not in the cecum
      or feces. Selenium was found in association with the bacterial cell fractions of
      gut contents and feces: 40-46% of the total Se was associated with colonic
      microbes and 58% in fecal microbes. Increased acetate and reduced butyrate
      production were driven by the addition of Se regardless of whether WB was fed.

PMID- 9164667
TI  - Determination of bromine and iodine in normal tissues from Beijing healthy
      adults.
AB  - The contents of bromine and iodine in samples of heart, liver, spleen, lung,
      muscle, and hair from healthy adults living in Beijing, China, were determined
      using epithermal neutron activation analysis. The results indicate that the
      contents of bromine in lung and iodine in liver are higher than those in other
      tissues, except human hair. The bromine contents in Beijing human tissues are
      significantly lower than those in other countries. The contents of iodine are
      slightly lower than those in other countries, but the difference is not
      significant. Three biological standard reference materials were simultaneously
      determined with the samples, and our results agree well with the certified
      values.

PMID- 9164668
TI  - Copper-specific damage in human erythrocytes exposed to oxidative stress.
AB  - Ascorbate and complexes of Cu(II) and Fe(III) are capable of generating
      significant levels of oxygen free radicals. Exposure of erythrocytes to such
      oxidative stress leads to increased levels of methemoglobin and extensive changes
      in cell morphology. Cu(II) per mole is much more effective than Fe(III). However,
      isolated hemoglobin is oxidized more rapidly and completely by Fe(III)- than by
      Cu(II)-complexes. Both Fe(III) and Cu(II) are capable of inhibiting a number of
      the key enzymes of erythrocyte metabolism. The mechanism for the enhanced
      activity of Cu(II) has not been previously established. Using intact erythrocytes
      and hemolysates we demonstrate that Cu(II)-, but not Fe(III)-complexes in the
      presence of ascorbate block NADH-methemoglobin reductase. Complexes of Cu(II)
      alone are not inhibitory. The relative inability of Fe(III)-complexes and
      ascorbate to cause methemoglobin accumulation is not owing to Fe(III) association
      with the membrane, or its failure to enter the erythrocytes. The toxicity of
      Cu(II) and ascorbate appears to be a result of site-specific oxidative damage of
      erythrocyte NADH-methemoglobin reductase and the enzyme's subsequent inability to
      reduce the oxidized hemoglobin.

PMID- 9164669
TI  - The serotonergic and noradrenergic systems of the hippocampus: their interactions
      and the effects of antidepressant treatments.
AB  - Previous reviews have well illustrated how antidepressant treatments can
      differentially alter several neurotransmitter systems in various brain areas.
      This review focuses on the effects of distinct classes of antidepressant
      treatments on the serotonergic and the noradrenergic systems of the hippocampus,
      which is one of the brain limbic areas thought to be relevant in depression: it
      illustrates the complexity of action of these treatments in a single brain area.
      First, the basic elements (receptors, second messengers, ion channels, ...) of
      the serotonergic and noradrenergic systems of the hippocampus are revisited and
      compared. Second, the extensive interactions occurring between the serotonergic
      and the noradrenergic systems of the brain are described. Finally, issues
      concerning the short- and long-term effects of antidepressant treatments on these
      systems are broadly discussed. Although there are some contradictions, the bulk
      of data suggests that antidepressant treatments work in the hippocampus by
      increasing and decreasing, respectively, serotonergic and noradrenergic
      neurotransmission. This hypothesis is discussed in the context of the purported
      function of the hippocampus in the formation of memory traces and emotion-related
      behaviors.

PMID- 9164670
TI  - The pressor reflex evoked by static contraction: neurochemistry at the site of
      the first synapse.
AB  - Stimulation of somatic sensory neurons activates the sympathetic nervous system,
      in turn enhancing cardiovascular function. This has been repeatedly demonstrated
      when afferent fibers arising from skeletal muscle serve as the sensory neurons.
      Over the past several years, studies have been performed examining the central
      nervous system (CNS) mechanisms that cause the reflex increases in arterial blood
      pressure and heart rate when skeletal muscle contracts. These studies have
      provided insights into how the CNS alters cardiovascular function, and have
      helped to enhance our understanding of central sensory transduction processes.
      Using a variety of techniques, several sites have been identified within the
      brain and spinal cord that are responsible for producing the reflex pressor
      response to static contraction. However, the purpose of this manuscript is to
      review the recent developments concerning only one CNS site: the dorsal horn of
      the spinal cord. This region serves as the first synapse for afferent fibers from
      skeletal muscle. The release of neurotransmitters, and possibly neuromodulators,
      into this region initiates the CNS component of this reflex. In addition, the
      magnitude of the reflex cardiovascular changes can be modulated at this site. The
      studies described in this review suggest that the dorsal horn of the spinal cord
      serves as an important site of integration for sensory signals that influence the
      cardiovascular system.

PMID- 9164671
TI  - Central nervous system complications of diabetes mellitus--a perspective from the
      blood-brain barrier.
AB  - A host of diabetes-related changes in the central nervous system (CNS) has been
      recognized. The underlying causes of these changes are multiple. An important
      contributor to the changes in the CNS is the blood-brain barrier (BBB). Diabetes
      is associated with changes in both the barrier and transport functions of the
      cerebral microvessels. Structural changes in cerebral microvessels may account
      for some of the observed changes. Additional mechanisms include alterations in
      hemodynamic variables such as arteriovenous shunting, changes in biophysical
      properties and biochemical compositions of the endothelial cells including
      changes in lipid fluidity and composition, and alterations of neurotransmitter
      activity in the cerebral microvessels, notably altered beta adrenergic
      neurotransmission. These observations indicate that the CNS is not immune against
      the microangiopathic complications commonly found in various tissues of diabetic
      animals.

PMID- 9164672
TI  - Zinc and Alzheimer's disease: is there a direct link?
AB  - Zinc is an essential trace element in human biology, but is neurotoxic at high
      concentrations. Several studies show that zinc promotes aggregations of beta
      amyloid protein, the main component of the senile plaques typically found in
      Alzheimer's disease brains. In other neurological disorders where neurons appear
      to be dying by apoptosis (gene-directed cell death), chelatable zinc accumulates
      in the perikarya of neurons before, or during degeneration. As there is evidence
      for apoptotic death of neurons in Alzheimer's disease, an involvement of zinc in
      this process needs to be investigated. Zinc interacts with enzymes and proteins,
      including transcription factors, which are critical for cell survival and could
      be linked to apoptotic processes. While controversial, some studies indicate that
      total tissue zinc is markedly reduced in several brain regions of Alzheimer's
      patients. At face value, it seems that a paradox exists between reports of a
      decrease in zinc in the Alzheimer's brain and the putative link to aberrant high
      zinc levels promoting plaque formation. An hypothesis to explain this
      inconsistency is presented. Neuropathological changes mediated by endogenous or
      exogenous stressors may be relevant factors affecting abnormal zinc metabolism.
      This paper reviews current investigations that suggest a role of zinc in the
      etiology of Alzheimer's disease.

PMID- 9164673
TI  - Sensory regulation of immediate-early gene expression in mammalian visual cortex:
      implications for functional mapping and neural plasticity.
AB  - The expression of immediate-early genes that code for transcription factors has
      been extensively studied in the brain with regard to imaging functional activity.
      The components of the AP-1 transcription factor--in particular, c-Fos--and Zif268
      have been widely used for this purpose. However, the precise details by which
      they are induced after synaptic stimulation remain unknown. Furthermore, the
      roles of these two proteins in neurons remains speculative and include such
      varied functions as short-term maintenance of cellular homeostasis to long-term
      changes that guide cortical plasticity. Current efforts at elucidating the
      physiological roles of AP-1 and Zif268 rely on assessing their expression in
      response to different conditions of sensory and pharmacological stimulation. In
      this review, we have examined the expression patterns of these transcription
      factors in the mammalian visual cortex under different conditions, with
      particular emphasis on the constitutive levels and how they change after visual
      deprivation and stimulation. A synthesis of this information offers further
      insight into their likely functions and the extent to which transcription factors
      may represent patterns of neural activity as a possible prelude to plastic
      events.

PMID- 9164674
TI  - Defining a role for c-Myc in breast tumorigenesis.
AB  - The proto-oncogene c-myc is commonly amplified and overexpressed in human breast
      tumors, and the tumorigenic potential of c-myc overexpression in mammary tissue
      has been confirmed by both in vitro and in vivo models of breast cancer. However,
      the mechanisms by which Myc promotes tumorigenesis are not well understood.
      Recent evidence indicates that Myc can promote cell proliferation as well as cell
      death via apoptosis. These studies provide new insight and impetus in defining a
      role for c-Myc in breast tumorigenesis and may point toward novel targets for
      breast cancer therapy.

PMID- 9164675
TI  - William L. McGuire Memorial Lecture. Antiestrogens: mechanisms of action and
      resistance in breast cancer.
AB  - Antiestrogens have proven to be highly effective in the treatment of hormone
      responsive breast cancer. However, resistance to antiestrogen therapy often
      develops. In addition, although tamoxifen-like antiestrogens are largely
      inhibitory and function as estrogen antagonists in breast cancer cells, they also
      have some estrogen-like activity in other cells of the body. Thus, recent efforts
      are being directed toward the development of even more tissue-selective
      antiestrogens, i.e. compounds that are antiestrogenic on breast and uterus while
      maintaining the beneficial estrogen-like actions on bone and the cardiovascular
      system. Efforts are also being directed toward understanding ligand structure
      estrogen receptor (ER) activity relationships and characterizing the molecular
      changes that underlie alterations in parallel signal transduction pathways that
      impact on the ER. Recent findings show that antiestrogens, which are known to
      exert most of their effects through the ER of breast cancer cells, contact a
      different set of amino acids in the hormone binding domain of the ER than those
      contacted by estrogen, and evoke a different receptor conformation that results
      in reduced or no transcriptional activity on most genes. Resistance to
      antiestrogen therapy may develop due to changes at the level of the ER itself,
      and at pre- and post-receptor points in the estrogen receptor-response pathway.
      Resistance could arise in at least four ways: (1) ER loss or mutation; (2) Post
      receptor alterations including changes in cAMP and phosphorylation pathways, or
      changes in coregulator and transcription factor interactions that affect the
      transcriptional activity of the ER; (3) Changes in growth factor
      production/sensitivity or paracrine cell-cell interactions; or (4)
      Pharmacological changes in the antiestrogen itself, including altered uptake and
      retention or metabolism of the antiestrogen. Model cell systems have been
      developed to study changes that accompany and define the antiestrogen resistant
      versus sensitive breast cancer phenotype. This information should lead to the
      development of antiestrogens with optimized tissue selectivity and agents to
      which resistance may develop more slowly. In addition, antiestrogens which work
      through somewhat different mechanisms of interaction with the ER should prove
      useful in treatment of some breast cancers that become resistant to a different
      category of antiestrogens.

PMID- 9164676
TI  - Histopathology grading in small breast cancers < or = 10 mm--results from an area
      with mammography screening.
AB  - Histopathological malignancy grading using the Bloom-Richardson classification of
      ductal cancers was performed for 248 invasive ductal breast cancers < or = 10 mm
      operated 1978-1985. There were significantly more grade 1 lesions in the
      prevalence screening round. Grade 3 was correlated with aneuploidy, higher S
      phase (SPF), and more receptor negative tumours. There were also significantly
      more positive lymph nodes in grade 3 lesions, 18% compared to 5% and 12%
      respectively for grades 1 and 2 (p < 0.05). In life table analysis for survival,
      when the high risk group of grade 3 lesions was compared to the grade 1 and 2
      lesions combined, five-year disease-free survival was 84.6% vs. 99.1% (p <
      0.001). With good training and care from the pathologist, malignancy grading
      seems useful for prognostication of eventual recurrence and death. In tumours 10
      mm or smaller only grade 3 lesions need to be included in follow-up systems and
      should probably have adjuvant treatment. Malignancy grading is especially good in
      small ductal breast cancers where grading can always be performed while other
      prognostic determinations are hampered by shortage of material. Lymph node
      positivity is also low in this group.

PMID- 9164677
TI  - Mechanism of action of a tyrphostin, 3,4-dihydroxy-alpha-cyanothiocinnamamide, in
      breast cancer cell growth inhibition involves the suppression of cyclin B1 and
      the functional activity of cyclin B1/p34cdc2 complex.
AB  - Tyrphostins are a group of compounds specifically targeted for the inhibition of
      tyrosine phosphorylation in signal transduction pathways. We studied the effects
      of a tyrphostin, 3,4-dihydroxy-alpha-cyanothiocinnamamide (tyrphostin-47), on
      hormone-responsive MCF-7 and hormone-unresponsive MCF-7-5C cell growth by DNA
      analysis for a period of 10 days. The growth of both cell lines was inhibited by
      this drug at 50 and 100 microM concentrations. Flow cytometric analysis showed
      that tyrphostin treatment caused a significant delay in the progression of MCF-7
      cells through G1 and S phases of the cell cycle. The level of cyclin B1, a
      component of the mitosis promoting factor (MPF), was reduced by 90% in the
      presence of 100 microM tyrphostin. The other component of MPF, p34cdc2 kinase,
      was not affected; however, its functional activity was dramatically reduced, as
      determined by histone H1 phosphorylation assay. In contrast, G1 cyclins (D1 and
      E) and tyrosine kinase activity were not markedly affected by tyrphostin-47, as
      determined by Western immunoblot detection with specific antibodies. Our results
      suggest that a possible mechanism of tyrphostin action in breast cancer cells
      might involve the suppression of cyclin B1 and inhibition of the functional
      activity of cyclin B1/p34cdc2 complex. Our data indicate that the cell cycle
      machinery might be a target for developing novel drugs for breast cancer.

PMID- 9164678
TI  - Androgens influence estrogen-induced responses in human breast carcinoma cells
      through cytochrome P450 aromatase.
AB  - The aromatase cytochrome P450 complex is responsible for the in vivo conversion
      of androgens to estrogens. Although breast cancer epithelial cells have been
      reported to have appreciable aromatase activity, its biologic significance
      remains uncertain. To address this, the effect of androgens on the expression of
      the estrogen-regulated gene pS2 in hormone-dependent human breast carcinoma cells
      in vitro was examined. Steroid-deprived MCF-7 cells were exposed to varying
      concentrations (1 nM, 10 nM, and 100 nM of androstenedione or testosterone for
      2,4, and 6 days. Baseline aromatase activity was 4.9 (+/-3.1) fmol
      3H2O/hour/microgram DNA [34.3 (+/-21.3) fmol/hr/10(6) cells] and was not
      influenced by the androgens. As an indication of estrogen biosynthesis, northern
      analysis was performed to quantitate pS2 mRNA expression. Although no significant
      pS2 induction was observed at 2 days, both 4 and 6 day exposure to 100 nM
      testosterone resulted in a 3-fold increase in pS2 mRNA expression. 5 alpha
      dihydrotestosterone (5 alpha-DHT) failed to elicit a similar pS2 response. This
      testosterone-induced response was inhibited with the aromatase inhibitor 7 alpha
      (4'-amino) phenylthio-1,4-androstadiene-3,17-dione (7 alpha-APTADD) and with 10
      microM tamoxifen. MCF-7 breast cancer cells possess endogenous aromatase activity
      at high enough levels to convert androgens to estrogens and elicit an estrogen
      induced response. The expression of aromatase may offer a potential advantage to
      hormone-responsive cells, providing an additional autocrine growth pathway which
      may be exploited.

PMID- 9164680
TI  - Trends in the incidence rate and risk factors for breast cancer in Japan.
AB  - The incidence rate of breast cancer in Japan rose more than two-fold from 1959-60
      to 1983-87. To assess to what extent this increase can be explained by changes in
      the prevalence of four major risk factors of breast cancer (i.e. age at menarche,
      age at first birth, age at menopause, and parity), we estimated the probability
      of developing breast cancer based on the joint distribution and relative risks of
      these four risk factors. The age-specific incidence rate during 1959-60 reported
      by the Miyagi Prefectural Cancer Registry was used to estimate the baseline
      hazard rate for women without the four risk factors in the same age group.
      Assuming that the baseline hazard rate is constant during all periods, we
      calculated the expected incidence rates during the periods of 1959-60, 1962-64,
      1968-71, 1973-77, 1978-81, and 1983-87 for each age group. Large discrepancies
      were noted between the observed and expected incidence rates during 1983-87 in
      all age groups. The change in the joint distribution of the four risk factors
      accounted for less than 40% of the increase observed from 1959-60 to 1983-87,
      suggesting the effects of other powerful risk factors.

PMID- 9164679
TI  - Cytological evaluation of biological prognostic markers from primary breast
      carcinomas.
AB  - This study was undertaken to evaluate our ability to detect multiple molecular
      markers of prognosis and response to treatment in fine needle aspirates (FNA)
      from patients with primary breast carcinomas. 147 patients with operable primary
      breast carcinomas who had been recruited to a randomized trial of primary medical
      therapy (PMT) versus adjuvant chemoendocrine therapy were analysed. FNAs were
      taken prior to therapy and from this multiple slides were produced using cytospin
      cytocentrifugation and stored at -80 degrees C for subsequent immunocytochemical
      analysis (ICA). ICA was performed for oestrogen receptor (ER), progesterone
      receptor (PgR), p53, Ki67, and Bcl-2. Part of the aspirate was snap frozen and
      used for flow cytometric analysis of ploidy and S-phase fraction (SPF). In a
      subgroup of 50 patients who had surgery prior to systemic therapy, as well as
      FNAs, sections were also taken from paraffin-embedded blocks and stained by ICA
      for ER, PgR and p53 for validation. In these patients ER was additionally
      measured by enzyme immunoassay (EIA) from frozen tissue taken at surgery. ER,
      PgR, p53, Bcl-2, and Ki67 were successfully detected by ICA while ploidy and SPF
      were successfully measured by flow cytometry from FNA material. The percentage
      positive values obtained were reasonable and as follows: 74% for ER, 70% for PgR,
      36% for p53, 80% for Bcl-2,68% of tumours were aneuploid and 32% diploid.
      Significant relationships between these measurements were observed in accordance
      with expectations. The concordance for ER, PgR, and p53 from FNA when compared to
      ICA of matching histological sections was 91.5%, 75.5%, and 75% respectively. For
      ER the concordance between measurement by ICA of cytological and histological
      samples and by EIA of frozen tissue was 82.5% and 84% respectively. These results
      indicate that multiple molecular markers can be adequately tested on cytological
      preparations from primary breast tumours. These markers can be used to determine
      prognosis and predict response to PMT.

PMID- 9164681
TI  - Urinary steroids at time of surgery in postmenopausal women with breast cancer.
AB  - Urinary steroid metabolites were measured by capillary gas chromatography in 22
      postmenopausal women with operable breast cancer on day before the tumour
      excision and in 20 hospitalised control who were before an operation from other
      cause than cancer. Serum dehydroepiandrosterone-sulphat (DHEAS) and testosterone
      (T) level were measured by radioimmunassay in the same groups and same time.
      There was no significant difference in the level of urinary androgen metabolites.
      Pregnanediol level was significantly lower (P < 0.05) in cancer patients. In the
      5 patients with positive axillary nodes the tetrahydrocortisol and alpha
      cortolone levels were significantly (P < 0.05) higher than in node negative ones.
      There was no significant differences in the serum DHEAS and T levels. These
      results indicate that metabolic changes are existing in postmenopausal patients
      which may be a cause or a consequence of the disease.

PMID- 9164682
TI  - Stereotactic radiosurgery.

PMID- 9164683
TI  - Temporal lobe epilepsy surgery in childhood: rationale for greater use.
AB  - Anterior temporal resection may effectively relieve therapy-resistant seizures in
      children and give social, psychological and economic benefits. Epidemiological
      and prognostic data demonstrate that this is an under-utilised procedure:
      although an estimated 677 Ontario children per year would be candidates for
      anterior temporal resection, only 18 were performed in a 12 month period.

PMID- 9164684
TI  - Radiosurgery for arteriovenous malformations: the University of Toronto
      experience.
AB  - BACKGROUND: From July 1989 to February 1996, 130 patients underwent stereotactic
      radiosurgery. We report the results of the first 50 patients eligible for a
      minimum of three years of follow-up. METHODS: Twenty women and 30 men, (mean age:
      37.5 years) were treated by dynamic rotation on a 6 MV linear accelerator. Prior
      treatment was embolization in seventeen, surgery in three and embolization and
      surgery in six. All had DSA and enhanced CT scanning, while some had MRI. Forty
      seven treatments used a single isodose. Restricting eloquent normal tissue to 15
      Gy, margin doses (at 50-90% isodose) were 12 Gy (one patient); 15 Gy (sixteen
      patients); 20 Gy (31 patients); 25 Gy (two patients). Maximum diameters were: <
      1.5 cm (12 patients); < 2.0 cm (nine patients); < 2.5 cm (twelve patients); < 3.0
      cm (thirteen patients; 3.0 cm (four patients). RESULTS: Forty-five patients were
      evaluable at three years, with thirty-nine having angiography. Twenty-five had
      angiographically confirmed obliterations; two had parenchymal AVMs obliterated
      but with residual dural components; four had MRI evidence of obliteration
      (refused angiography). One patient acutely had a seizure; one patient (with
      hemorrhages, resection, and embolizations preceding two applications of
      radiosurgery, separated by 3.5 years) had worsening of memory. CONCLUSIONS: Our
      uncorrected (five patients unevaluable at three years) and corrected
      angiographically confirmed obliteration rates are 54% and 60% respectively. Our
      follow-up (98% accounting of cohort; 78% angiographic rate) and explicit
      derivation of denominators help delineate the efficacy of radiosurgery at these
      doses.

PMID- 9164685
TI  - Prediction of obliteration of arteriovenous malformations after radiosurgery: the
      obliteration prediction index.
AB  - OBJECTIVE: To describe the response to single dose photon stereotactic
      radiosurgery of arteriovenous malformations (AVMs) so that the probability of
      success or failure of treatment may be predicted for the individual patient.
      METHOD: The obliteration prediction index (OPI) was calculated for AVMs by
      dividing the marginal dose of radiation in Gray (Gy) by the lesion diameter in
      centimetres in cohorts of 42 patients treated with the modified linear
      accelerator at Toronto-Sunnybrook Regional Cancer Centre and 394 patients treated
      with the gamma unit at the Royal Hallamshire Hospital, Sheffield, United Kingdom.
      Patients were grouped into ranges by OPI and the proportion of success and
      failure was calculated for each group. An exponential function [P = 1-A.e(
      B.OPI)] was fitted to the data by the least squares method. RESULTS: Despite
      systematic differences in radiation treatment, that is, marginal doses of 15 and
      20 Gy in Toronto and most Sheffield patients with a marginal dose of 25 Gy, the
      resultant data points exhibited similar behaviour. CONCLUSION: The function [P =
      1-A.e(-B.OPI)] partly describes the biological effect of radiation and is
      independent of the radiation device used. Radiosurgery centres can use this model
      to facilitate predictions of successful treatment for individual patients.

PMID- 9164686
TI  - Radiosurgery and accelerated radiotherapy for patients with glioblastoma.
AB  - OBJECTIVE: To assess the feasibility, toxicity, and local control of stereotactic
      radiosurgery followed by accelerated external beam radiotherapy (AEBR) for
      patients with glioblastoma multiforme. MATERIALS AND METHODS: Six males and eight
      females, with a median age of 67.5 years (range 45-78 years), entered the study.
      Karnofsky performance status was 90 for five, 80 for six, and 60 for three
      patients. Following surgery, the patients were left with a residual mass 4 cm.
      Radiosurgery was delivered with a single dose of 20 Gy to the 90% isodose surface
      corresponding to the contrast-enhancing edge of the tumour. A total AEBR dose of
      60 Gy in 30 fractions was delivered using a concomitant boost technique over four
      weeks. RESULTS: Median survival time was 40 weeks (range 17-80 weeks). Actuarial
      survivals at 12 and 18 months were 43% and 14%, respectively. The median time to
      progression was 25 weeks (range 2-77 weeks). One patient developed a seizure on
      the day of stereotactic radiosurgery. Two patients experienced somnolence at 47
      and 67 days post-radiotherapy. Eight patients remained steroid-dependent.
      Radiological evidence of leukoencephalopathy was observed in one patient, and
      brain necrosis in two additional patients at 30 and 63 weeks. One of these two
      patients with brain necrosis developed complete loss of vision in one eye, and
      decreased vision in the contralateral eye at 63 weeks. CONCLUSION: Stereotactic
      radiosurgery followed by AEBR was feasible but was associated with late
      complications. The use of such radiosurgical boost for patients with glioblastoma
      multiforme should be reserved for those patients entering controlled clinical
      trials.

PMID- 9164687
TI  - Somatosensory evoked potential identification of sensorimotor cortex in removal
      of intracranial neoplasms.
AB  - OBJECTIVE: To assess the ease and reliability of routine use of somatosensory
      evoked potentials (SSEPs) for identification of sensorimotor cortex in brain
      tumour removal and to document its influence on the performance and outcome of
      surgery. METHODS: SSEPs in response to contralateral median nerve stimulation
      were recorded from the cortical surface by means of a four lead electrode strip.
      Polarity reversal of short latency SSEP waves was used to identify the position
      of the central sulcus in 46 consecutive craniotomies for removal of metastases,
      gliomas, or meningiomas located in, near, or overlying sensorimotor cortex.
      RESULTS: SSEPs were successfully recorded in 43/46 cases (94%) with demonstration
      of polarity reversal in 42/43 (98%). SSEP localization led to modification of
      14/42 (33%) procedures, most frequently because of either displacement or
      involvement of sensorimotor cortex by tumour. Six patients (14%) developed new
      neurological deficits but none of these was attributable to incorrect
      identification of sensorimotor cortex. CONCLUSIONS: SSEP polarity reversal is a
      simple, reliable, accurate, and inexpensive method of localizing sensorimotor
      cortex under general anaesthesia. Correct identification is possible when
      sensorimotor cortex is displaced or when surface anatomy is obscured by tumour.
      Routine use of this technique should be considered in all procedures for lesions
      located near the central sulcus.

PMID- 9164688
TI  - Neuropathological changes in chronic adult hydrocephalus: cortical biopsies and
      autopsy findings.
AB  - BACKGROUND: The cortical changes resulting from chronic hydrocephalus in adults
      are not well defined. METHODS: Retrospective analysis of twenty-one patients (age
      64-88 years) with a clinical diagnosis of "normal pressure hydrocephalus" who
      underwent cortical biopsy at the time of intracranial pressure monitoring or
      shunt insertion, and eight patients who were biopsied but not shunted. Eleven
      brains (age 26-92 years), seven from patients who could be considered to have
      "normal pressure hydrocephalus", were also examined following autopsy. Age- and
      sex-matched control brains with small ventricles and no history of dementia were
      compared to the hydrocephalic brains. Senile plaques and neurofibrillary tangles
      were assessed semiquantitatively and a non-parametric statistical analysis was
      employed. RESULTS: Five biopsies exhibited both senile plaques and rare
      neurofibrillary tangles, while two had only neurofibrillary tangles.
      Neurofibrillary tangles were more prevalent in hydrocephalic brains than in
      controls. There was no difference in the prevalence of senile plaques between the
      two groups. Grumose bodies in the substantia nigra were identified in five
      autopsy brains, a prevalence higher than in control brains. CONCLUSIONS: These
      pathological features are not specific for hydrocephalus; however, they suggest
      that long-standing ventriculomegaly is associated with degenerative brain changes
      in sites beyond the periventricular white matter. The presence of senile plaques
      in cortical biopsies from hydrocephalic patients does not appear to be a
      contraindication to shunting; however a prospective study in patients undergoing
      intracranial pressure monitoring would better address the issue.

PMID- 9164689
TI  - "Familial Parkinson's disease"--a case-control study of families.
AB  - BACKGROUND: Parkinson's disease (PD) patients frequently report a family history
      of PD and this may provide etiological clues to PD. It has also been suggested
      that a report of a negative family history is reliable. We studied the prevalence
      of PD in relatives of PD patients to assess the reliability of family history and
      to evaluate possible explanations of "familial PD" (fPD). METHODS: 81 of 650
      (12.5%) PD probands (all PD patients seen at clinic in 4 years) reported a
      positive family history of PD. Each fPD proband was matched with non-familial PD
      (nfPD) proband by gender and year of birth. Screening and follow-up
      questionnaires were mailed to relatives to obtain information concerning pedigree
      and presence of neurodegenerative disease. Available family members (regardless
      of disease status) were examined. RESULTS: On examination, 8 persons, said to be
      "normal" by probands, relatives and themselves, had definite or possible PD (5
      fPD, 3 nfPD). The prevalence rate of PD among first and second degree living
      relatives of probands varied significantly between fPD and nfPD groups
      (6269/100,000 versus 1190/100,000; p < 0.001). The weighted prevalence (taking
      into account the proportions of fPD and nfPD within the clinic) was 1822/100,000,
      a value more than 5 times higher than reported prevalence rates of PD in the
      general population (p < 0.001). The prevalence rate was greater in first degree
      relatives than second degree. CONCLUSIONS: "Familial parkinsonism" cannot be
      explained merely by size of or advanced age within families. Significant numbers
      of previously unrecognized PD patients may be identified despite a "negative"
      family history. That is, the patient's report of an absence of familial
      parkinsonism is frequently inaccurate. The prevalence rate in relatives of PD
      patients appears to be higher than the general population-regardless of the
      family history reported by a PD patient. We believe our study suggests that
      genetic influences or early life environmental exposures are likely to be of
      etiological importance in PD.

PMID- 9164690
TI  - Pallidotomy increases cortical inhibition in Parkinson's disease.
AB  - BACKGROUND: Pallidotomy helps parkinsonian symptoms. We tested the hypothesis
      that this might be due to changes in inhibition in the motor cortex. METHODS: We
      examined 15 patients with parkinsonism before and after posteroventral
      pallidotomy. Magnetic stimuli were delivered over the motor cortex, while
      subjects maintained a 30% maximum voluntary contraction of the contralateral
      first dorsal interosseus (FDI). RESULTS: Weak stimuli inhibited voluntary muscle
      activity, while slightly stronger stimuli caused short latency facilitation from
      activation of the corticospinal neurons. After pallidotomy magnetic stimulation,
      at the threshold for the short latency facilitation, resulted in more inhibition
      than before. CONCLUSION: Pallidotomy increases cortical inhibition. This may be
      associated with improved control of movements.

PMID- 9164691
TI  - Varicella zoster antibodies after herpes zoster, varicella and multiple
      sclerosis.
AB  - BACKGROUND: We previously showed that Manitoba Hutterites seek physician care for
      varicella zoster virus infection significantly less than non-Hutterites. The
      current study was undertaken to measure varicella zoster virus seroprevalence for
      Hutterite and non-Hutterite controls. METHODS: Blood was obtained from 315
      Hutterites and 259 similar age and sex controls at the time of blood donations to
      The Canadian Red Cross Society. The controls were from the same or a contiguous
      postal code area and were collected at the same time as the Hutterite samples.
      The immune status of the specimens was determined by the ELISA method (enzyme
      linked immunosorbent assay). RESULTS: Twenty-eight per cent of 315 Hutterites had
      no immunity and an additional 25% had only marginal immunity. Among the 259
      controls, 10% had no immunity and an additional 10% had only marginal immunity (p
      < .0001). CONCLUSIONS: Manitoba Hutterites have significantly decreased
      seroprevalence to varicella zoster virus infection. This study of serum varicella
      zoster virus antibodies verifies a previous population based study that
      demonstrated the relative rarity of varicella and herpes zoster among a
      particular population group.

PMID- 9164692
TI  - A randomized, controlled trial of linopirdine in the treatment of Alzheimer's
      disease.
AB  - OBJECTIVES: We tested the efficacy and safety of linopirdine, a novel
      phenylindolinone, in the treatment of Alzheimer's disease. METHODS: A
      multicentre, randomized, double-blind, parallel group, placebo-controlled trial
      of linopirdine (30 mg three times per day or placebo). Patients (n = 382, 55%
      male, 98% Caucasian, age range 51-95 years) with mild or moderate Alzheimer's
      disease, of whom 375 received at least one treatment dose were analysed. There
      were no important differences between the groups at baseline. RESULTS: No
      difference was seen in Clinical Global Impression scores between patients
      receiving placebo and those receiving linopirdine (n = 189). Small differences in
      the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores
      were seen throughout the study favouring linopirdine; at 6 months the ADAS-Cog
      scores were 20.2 (linopirdine) and 22.1 (placebo) p = 0.01. CONCLUSIONS: This
      trial did not detect clinically meaningful differences in patients receiving
      linopirdine for 6 months, despite evidence of a small degree of improved
      cognitive function. Further studies may benefit from more sensitive tests of
      treatment effects in Alzheimer's disease.

PMID- 9164693
TI  - A rare form of adult onset leukodystrophy: orthochromatic leukodystrophy with
      pigmented glia.
AB  - BACKGROUND: Orthochromatic leukodystrophy with pigmented glia and scavenger cells
      is a rare leukodystrophy of unknown etiology. This report describes a 42-year-old
      man with a history of depression, dementia and parkinsonism having the
      pathological features of orthochromatic leukodystrophy with pigmented glia.
      METHODS: We reviewed the clinical history and pathology of autopsy and brain
      biopsy material. RESULTS: Imaging revealed bilateral cerebral white matter
      hypodensities. At autopsy, the brain demonstrated a leukodystrophy affecting
      predominantly the cerebral hemispheres and characterized by demyelination, and
      cytoplasmic pigment deposits in oligodendroglia and astrocytes. The pigment had
      the staining properties of ceroid-lipofuschin and on ultrastructural examination
      was composed of membrane-bound lipid and electron-dense inclusions which had a
      fingerprint-like pattern. Similar pigment inclusions were not observed on
      ultrastructural examination of renal, splenic or hepatic tissue obtained at
      autopsy. The brain biopsy contained cerebral cortex with sparse subcortical white
      matter in which a few oligodendroglia and fewer astrocytes at the grey/white
      junctions showed cytoplasmic pigmentary inclusions identical to those described
      above. However, due to the paucity of white matter in the specimen a definite
      diagnosis of orthochromatic leukodystrophy with pigmented glia was not made.
      CONCLUSIONS: The diagnosis of orthochromatic leukodystrophy with pigmented glia
      and scavenger cells can only be made antemortem if the brain biopsy contains
      adequate white matter and although a rare condition, it should be considered in
      the differential diagnosis of an adult onset leukodystrophy.

PMID- 9164694
TI  - Tissue plasminogen activator in a vertebral artery dissection.
AB  - BACKGROUND: Spontaneous dissection of the vertebral artery is uncommon. METHOD:
      Case study. RESULTS: We report a 49-year-old woman who presented with the rapidly
      progressing basilar artery syndrome who was given an intravenous dose of tissue
      plasminogen activator seven hours after the onset of first symptoms. Thirty
      minutes after the injection, a dramatic recovery of the patient's consciousness
      and neurological signs was noted. CONCLUSION: To our knowledge, this is the first
      reported case of intravenous tissue plasminogen activator use in acute vertebral
      artery dissection.

PMID- 9164695
TI  - Lhermitte-Duclos disease: literature review and novel treatment strategy.
AB  - BACKGROUND: Lhermitte-Duclos disease (LDD) is a rare pathologic entity involving
      the cerebellum. The fundamental nature of the entity and its pathogenesis remain
      unknown, and considerable debate has centered on whether it represents a
      neoplastic, malformative or hamartomatous lesion. The cell or cells of origin
      remain incompletely defined. Previous reports of cases in the English literature
      have dealt predominantly with the clinical and pathological aspects yet few
      address issues of treatment. METHODS: A case of Lhermitte-Duclos disease (LDD) in
      a 54-year-old female leading to local compressive symptoms and obstructive
      hydrocephalus is presented. A craniectomy, in addition to a C1 laminectomy
      followed by a decompressive duroplasty (using autologous fascia lata graft) was
      performed. RESULTS: The patient clinically improved and follow-up MRI 11 months
      post-operatively revealed improvement in hydrocephalus. CONCLUSION: The
      histological and immunohistochemical features of the lesion are described,
      emphasizing the role of an abnormal dysplastic granule cell layer. The evidence
      in favor of each of the major theories of pathogenesis, malformative and
      neoplastic is discussed. Based on these facts a form of surgical intervention
      involving decompressive duroplasty is proposed.

PMID- 9164696
TI  - Current management of aneurysmal subarachnoid hemorrhage guidelines from the
      Canadian Neurosurgical Society.
AB  - Published medical evidence pertaining to the management of aneurysmal
      subarachnoid hemorrhage (SAH) was critically reviewed in order to prepare
      practice guidelines for this condition. SAH should be considered as a possible
      cause of all sudden and/or unusual headaches, and every attempt should be made to
      recognize mild SAHs, as they are still frequently misdiagnosed. The first test
      for SAH is computed tomography (CT), followed by lumbar puncture when the CT is
      negative for intracranial bleeding (the case in only several per cent of patients
      within 24 hours of aneurysm bleeding). Urgent cerebral angiography is necessary
      to detect the underlying cerebral aneurysm. The advantage of rapid diagnosis of
      SAH followed by early aneurysm repair is minimizing the risk of catastrophic
      aneurysm rebleeding. Early surgery for aneurysm repair is often possible and is
      recommended, unless the aneurysm location or size renders it technically
      difficult to expose in clot-laden subarachnoid cisterns beneath an acutely
      swollen brain. Aneurysm ablation is optimally accomplished with open microsurgery
      and clipping of the aneurysm neck, although other options include proximal parent
      artery occlusion, "trapping" of the aneurysmal segment of the artery, and
      embolization of thrombogenic materials (e.g., platinum "microcoils") directly
      into the aneurysm dome using endovascular techniques. Neurological outcome
      following SAH is also optimized through the prevention of secondary SAH
      complications, and further management specific for ruptured cerebral aneurysms
      can include anticonvulsants, neuroprotectants, and various agents and techniques
      to prevent or reverse delayed-onset cerebral vasospasm. All patients with
      aneurysmal SAH should be treated with the calcium antagonist nimodipine, and in
      certain circumstances patients should receive anticonvulsants. Induced arterial
      hypertension, hypervolemia and in some instances percutaneous balloon angioplasty
      are recommended to reverse vasospasm causing symptomatic cerebral ischemia prior
      to cerebral infarction.

PMID- 9164697
TI  - CYP2D6-related oxidation polymorphism in a Canadian Inuit population.
AB  - The xenobiotic oxidation polymorphism associated with cytochrome P450 2D6
      (CYP2D6) was investigated in 152 genetically related and unrelated healthy Inuit
      subjects living in the High Arctic of eastern Canada. Phenotyping was based on
      HPLC determination of the CYP2D6-related dextromethorphan metabolic ratio in
      overnight urine samples after oral administration of 30 mg dextromethorphan
      hydrobromide. The log metabolic ratio was bimodally distributed, with three
      subjects classified as poor metabolizers (PMs). In subjects unrelated in the
      first degree, the incidence of the PM phenotype was 3 of 90 or 3.3%. PCR-based
      analyses of DNA for variants of the CYP2D6 gene demonstrated that the PMs of
      dextromethorphan had the defective allele CYP2D6*4. The estimated frequency of
      the CYP2D6*4 allele was 0.067-0.083, which is lower than the frequency in
      Caucasians but higher than the frequency in Oriental populations. The CYP2D6*3
      and the CYP2D6*6 alleles were not detected in the Inuit population. The CYP2D6*10
      allele was present in only four unrelated subjects, classified as extensive
      metabolizers (EMs), resulting in an estimated allele frequency of 0.022, which is
      much lower than in Oriental populations. This study demonstrated the existence of
      the CYP2D6 polymorphism in Canadian Inuit, while the frequencies of allelic
      variants of CYP2D6 point to the uniqueness of this population. Several important
      therapeutic drugs that are being prescribed in Arctic communities will have
      altered pharmacokinetics in PMs of CYP2D6.

PMID- 9164698
TI  - Differential effects of pharmacologically generated reactive oxygen species upon
      functional activity of epididymal mouse spermatozoa.
AB  - Several studies indicate that reactive oxygen species (ROS) are involved in
      defective sperm function pathophysiology. In this study we attempted to determine
      differentially the effects of xanthine (0.12 mM) plus xanthine oxidase (0.035
      U/mL) (X+XO, a ROS promoter system), ROS scavengers (Tiron (TIR, 15 mM); catalase
      (CAT, 10 micrograms/mL); dimethylsulfoxide (DMSO, 140 mM)), and X+XO plus
      scavengers on several epididymal mouse spermatozoa functional parameters,
      incubated in NTPC medium, for 29 min. In the presence of X+XO, progressive
      gametes significantly diminished. TIR or CAT attenuated this effect, but DMSO did
      not. Inversely, X+XO increased the bending-forms population; only TIR reversed
      this phenomenon. The ROS promoter system diminished the viable cell population;
      all scavengers assayed maintained sperm viability at levels similar to control
      ones. When exposed to hypoosmotic shock after 29 min incubation with X+XO, the
      percentage of swollen cells decreased; TIR, CAT, or DMSO did not prevent this
      effect. Our experiments demonstrate that it is possible to differentiate the
      deleterious ROS effects upon sperm functional activity. O-2. and H2O2
      preferentially seem to modify sperm motility, O-2. exhibiting the greatest
      ability for generating bending-form gametes, OH-being the most lethal ROS. In
      addition, sperm membrane clearly appears as the most damaged structure.

PMID- 9164699
TI  - Increased alanine uptake and lipid synthesis from alanine in isolated hepatocytes
      of Wistar-Kyoto fatty rats: an inhibitory effect of biguanides.
AB  - To examine the pathophysiological characteristics of non-insulin-dependent
      diabetes mellitus, alanine metabolism in isolated hepatocytes of male Wistar
      Kyoto (WKY) fatty rats (genetically obese and hyperglycemic) and their lean
      littermates was investigated. The effects of glucagon and the biguanides,
      metformin and buformin, on alanine metabolism were also studied by measuring
      alanine uptake and lipid synthesis from alanine. WKY fatty rats showed higher
      plasma insulin and lipid concentrations than lean rats at 5 as well as at 12
      weeks of age. Alanine uptake into hepatocytes was increased in fatty rats only at
      12 weeks of age compared with lean rats. Lipid synthesis from alanine in
      hepatocytes was increased in fatty rats at 5 and 12 weeks of age compared with
      lean rats. Glucagon increased alanine uptake into hepatocytes but did not affect
      lipid synthesis from alanine in both fatty and lean rats. Low concentrations (0.1
      mM) of biguanides decreased lipid synthesis from alanine only in fatty rats
      without inhibiting alanine uptake into hepatocytes. These observations suggest
      that lipid synthesis from alanine in hepatocytes of WKY fatty rats is accelerated
      prior to the onset of diabetes mellitus, which might be associated with the
      development of diabetes, and that an inhibitory effect on increased lipid
      synthesis is one of the pharmacodynamic actions of biguanides.

PMID- 9164700
TI  - Urinary excretion of benzo[a]pyrene metabolites following intravenous, oral, and
      cutaneous benzo[a]pyrene administration.
AB  - The effect of the administration route, dose, and sampling time on the total
      urinary excretion of four major benzo[a]pyrene (BaP) metabolites, 3-hydroxyBaP (3
      OHBaP), 9-hydroxyBaP 9-hydroxyBaP (9-OHBaP), trans-4,5-dihydrodiolBaP (4,5
      diolBaP), and trans-9,10-dihydrodiolBaP (9,10-diolBaP), was studied in male
      Sprague-Dawley rats exposed to a single intravenous, oral, and cutaneous dose of
      2, 6, 20, and 60 mumol BaP/kg. Urine samples were collected at 24-h intervals
      following treatment. Over the 0-72 h period and for a given dose, amounts of BaP
      metabolites were 3-OHBaP > 4,5-diolBaP > > 9-OHBaP following intravenous and oral
      dosing, and 3-OHBaP > > 9-OHBaP > or = 4,5-diolBaP after cutaneous treatment.
      9,10-diolBaP was barely detected. On the other hand, amounts of 3-OHBaP and 4,5
      diolBaP excreted in urine over the 0-72 h period and for a given dose appeared in
      the following order: intravenous approximately oral > or = cutaneous. Amounts of
      9-OHBaP excreted varied as follows: oral > or = cutaneous > intravenous. For all
      routes of administration, excretion of 4,5-diolBaP was almost complete over the 0
      24 h period in contrast with 3-OHBaP and 9-OHBaP. Peak excretion of 3-OHBaP and 9
      OHBaP was reached in the 0-24 h period following intravenous and oral treatment
      and in the 24-48 h period following cutaneous application. Overall, for a given
      administration route and dose, there were variations in the time profiles between
      metabolites. In general, there was nonetheless a good correlation between the BaP
      dose and urinary excretion of 3-OHBaP, 9-OHBaP, and 4,5-diolBaP. Furthermore,
      total urinary excretion of a specific metabolite, its time profile, and the
      relative proportion of the metabolites studied depended on the administration
      route. Data also suggest that a measure of the concentration ratio of the
      different metabolites could reflect the time and main route of exposure.

PMID- 9164701
TI  - Transport of albumin into the intestinal lumen of the rat.
AB  - The intestine is considered a major site for the breakdown and clearance of serum
      proteins. The mechanism of transport of macromolecules from the serosa into the
      lumen is unclear. The present study was designed to characterize the serosal to
      mucosal movement of albumin. Transport of bovine serum albumin (BSA) was assessed
      in short-circuited Ussing chambers, using stripped rat jejunum devoid of Peyer's
      patches. To define the kinetics of serosal to mucosal albumin transport the
      serosal surface was exposed to BSA at varying concentrations (0.5-5 mg.mL-1).
      Fluids from the mucosal compartment were sampled over time and assayed for
      immunologically intact BSA by ELISA. All subsequent experiments utilized a
      concentration of cold BSA (2 mg.mL-1) that produced maximal levels of intact BSA
      transport. To assess total BSA transport (intact BSA plus degraded BSA), 10
      microCi (1 Ci = 37 GBq) 125I-labelled BSA was added to the serosal surface in
      addition to 2 mg.mL-1 cold BSA. To further characterize BSA transport tissues
      were treated with sodium fluoride (NaF) (metabolic inhibitor) or colchicine (an
      inhibitor of microtubule polymerization) or with the nerve blocker tetrodotoxin
      (TTX). All experiments using inhibitors were performed in paired tissues obtained
      from the same animal. Transport of intact BSA into the intestinal lumen was a
      saturable process, with a Vmax of 251 +/- 13 ng.cm-2.h-1 and a Km of 0.72 +/- 0.1
      mg.mL-1, and represented 7% of the total BSA flux into the intestinal lumen. In
      the presence of NaF (2 x 10(-3) M), transport of both intact and total BSA was
      significantly inhibited (intact: control 374 +/- 80 vs. NaF 46 +/- 11, 88%
      inhibition; total: control 3288 +/- 296 vs. NaF 2550 +/- 235 ng.cm-2.h-1, 22%
      inhibition; p < 0.05). In addition, colchicine significantly inhibited intact BSA
      transport (control 339 +/- 15 vs. colchicine 206 +/- 13 ng.cm-2.h-1, 39%
      inhibition; p < 0.05). TTX had no effect on intact BSA flux. The findings suggest
      that transport of intact BSA from the serosa into the intestinal lumen is a
      saturable, energy-dependent process, which involves microtubules but is not under
      neural regulation.

PMID- 9164702
TI  - Effect of melittin on the apical membrane Na+ and Cl- conductances of frog cornea
      epithelium.
AB  - The transepithelial conductance increased with 10(-6) M melittin on the tear side
      of the frog cornea. This effect was attributed to the opening of an apical
      membrane Na+ conductance. However, the potency of the venom at this concentration
      (apical membrane fractional resistance (fRo) decreased to near zero) masked this
      and other effects. With 3 x 10(-7) M on the tear side, the effects were finite
      (fRo > 0) and reversible. With fRo > 0, the effects of melittin could be readily
      studied on the transport parameters of Na+, Cl-, and K+. Epithelial cells of
      intact bullfrog corneas were impaled with microelectrodes using an in vitro
      preparation. Under short-circuit current (Isc) conditions, 20 min after melittin
      Isc increased by 3.1 from 8.2 microA/cm2., fRo decreased by 18 from 51%; the
      intracellular potential, Vo, depolarized by 19.4 from -56.5 mV; and the
      transepithelial conductance, gv increased by 0.57 from 0.29 mS/cm2. Tenfold
      decreases in tear Na+ or Cl- concentrations changed the transport parameters
      consistent with the formation of a Na+ conductance and an increase in the apical
      membrane Cl- conductance by the venom. These conclusions were further supported
      by the minimal effect of melittin in Cl(-)-fre and, particularly, in Na(+)-free
      solutions. Changes in K+ concentration had no effect on transport parameters.
      These findings indicate that the effect of melittin at this low concentration is
      upon a Na+ channel protein and not due to nonspecific conductances.

PMID- 9164703
TI  - Citrulline malate limits increase in muscle fatigue induced by bacterial
      endotoxins.
AB  - Citrulline malate is known to improve performance in weakened muscles. The
      present experiment was designed to test the hypothesis that citrulline malate can
      limit the effect of endotoxins on muscle fatigability. Endotoxemia was induced in
      rats by injection of lipopolysaccharides from Klebsiella pneumoniae. Resistance
      to fatigue was quantified by measuring tension production during repetitive
      electrical stimulation of the isolated epitrochlearis muscle. Oral treatment by
      citrulline malate was found to increase resistance to fatigue in infected rats,
      whereas twitch tension was not modified. This demonstrates the efficacy of
      citrulline malate for limiting an increase in muscle fatigue elicited with
      bacterial endotoxins.

PMID- 9164704
TI  - Trans fatty acids, lipoproteins, and coronary risk.
AB  - Most dietary fatty acids contain at least one double bond, which is usually in
      the cis configuration. However, biohydrogenation in the rumen of cows and sheep,
      or catalytic hydrogenation of vegetable oils in the food industries, will convert
      some of the cis double bonds to the trans configuration. Trans fatty acid intake
      in western Europe and North America probably ranges from 5 to 15 g/day. Major
      dietary sources are frying fats used in industrial food preparation, margarines,
      and other spreads. In the past, margarines contained up to 50% trans fatty acids;
      however, these are now being phased out. Trans fatty acids raise serum low
      density lipoprotein (LDL) cholesterol and lower high density lipoprotein (HDL)
      cholesterol in humans when substituted for cis unsaturated fatty acids in the
      diet. These effects may be mediated by the cholesteryl ester transfer protein.
      Trans fatty acids also increase lipoprotein (a) levels relative to other fatty
      acids. The effects of trans fatty acids on the risk profile for coronary heart
      disease are thus unfavorable, and labels of food products should state the trans
      fatty acid content.

PMID- 9164705
TI  - Dietary phytosterols as cholesterol-lowering agents in humans.
AB  - Phytosterols (plant sterols), abundant in fat-soluble fractions of plants, are
      consumed at levels of 200-400 mg/day in Western diets. Chemically resembling
      cholesterol, phytosterols inhibit the absorption of cholesterol. Phytosterol
      consumption in human subjects under a wide range of study conditions has been
      shown to reduce plasma total and low density lipoprotein (LDL) cholesterol
      levels; however, the response varies widely. Greater cholesterol-lowering
      efficacy occurs with consumption of the saturated phytosterol sitostanol versus
      sitosterol or campesterol. Most studies report no effect of phytosterol
      administration in high density lipoprotein (HDL) cholesterol or triglyceride
      levels, although certain evidence exists for an HDL cholesterol raising effect of
      sitostanol. Phytosterol absorption is limited, although serum phytosterol levels
      have proven to be important indicators of both cholesterol absorption and
      synthesis. Serum phytosterols correlate with HDL cholesterol level. In addition,
      higher phytosterol/cholesterol ratios appear in HDL versus LDL particles,
      suggesting the existence of an intrinsic phytosterol action, in addition to the
      extrinsic effect on cholesterol absorption. In conclusion, addition to diet of
      the phytosterol sitostanol represents an effective means of improving circulating
      lipid profiles to reduce risk of coronary heart disease.

PMID- 9164706
TI  - Dietary antioxidants and cardioprotection--fact or fallacy?
AB  - The emerging dogma that low density lipoprotein (LDL) oxidation is a contributing
      cause and not simply a consequence of atherosclerosis is based on three lines of
      experimental evidence: (i) lipid peroxidation products and oxidized LDLs are
      present in atherosclerotic lesions; (ii) oxidized LDL has an array of potentially
      proatherogenic properties in vitro, including uptake by macrophages via a number
      of distinct "scavenger" receptors; and (iii) treatment of hypercholesterolemic
      animals with potent antioxidant drugs can retard the development of
      atherosclerosis. Additional support for the role of lipoprotein oxidation in
      atherogenesis was provided by cross-cultural dietary comparisons, which suggested
      an inverse correlation between antioxidant vitamin intake and coronary mortality.
      As well, several large case-control studies indicated that antioxidant vitamin
      intake, particularly vitamin E, was associated with reduced coronary risk.
      However, these studies do not indicate whether this association is causal, or if
      vitamin supplementation is merely a marker for some other protective factor. To
      test this properly, randomized controlled intervention studies are required. In
      several animal models, a number of different antioxidant drugs have been shown to
      retard atherosclerosis, but results with vitamin supplementation are unclear.
      Results of intervention trials in humans show no benefit to long-term beta
      carotene supplementation, and the only published study of vitamin E found a
      reduction of nonfatal myocardial infarction but no reduction (actually an
      increase) in fatal myocardial infarction and total mortality. Several other large
      antioxidant intervention trials are underway. Until the results of these studies
      are available, there appears to be insufficient evidence on which to base
      recommendations regarding antioxidant supplements for the prevention of
      atherosclerosis.

PMID- 9164707
TI  - Omega-3 fatty acids in the prevention-management of cardiovascular disease.
AB  - Epidemiologic studies show that populations who eat fish versus those who do not
      have a reduced death rate from cardiovascular disease. Experimental studies have
      shown that omega-3 fatty acids affect the function of cells involved in
      atherothrombosis in numerous ways, including the modification of eicosanoid
      products in the cyclooxygenase and lipoxygenase pathways, the reduced synthesis
      of cytokines and platelet-derived growth factor, and alterations of leukocyte and
      endothelial cell properties. Intervention studies in patients with restenosis,
      myocardial infarction, and cardiac arrhythmias with omega-3 fatty acid
      supplementation have been addressed in several clinical studies. The ingestion of
      omega-3 fatty acids following one episode of myocardial infarction appears to
      decrease the rate of cardiac death. These effects of omega-3 fatty acids appear
      to be due to their antiarrhythmic properties. In fact, fish oil has been shown to
      reduce ventricular arrhythmias and to be more beneficial than currently used
      pharmacologic agents. The dose, duration, and mechanisms involved in the
      prevention and management of cardiovascular disease following omega-3 fatty acid
      ingestion or supplementation need to be investigated by double blind controlled
      clinical trials.

PMID- 9164708
TI  - Clinical approach to diagnosis of syncope. An Overview.
AB  - Effective management of the syncope patient is critically dependent on excluding
      conditions in which altered consciousness is not due to syncope (e.g., seizure
      and sleep disorders) then establishing the basis for syncopal symptoms. The
      initial diagnostic step in syncope patients is differentiation of those
      individuals with normal cardiovascular status from those with structural heart
      disease. In the former, tilt-table testing and related studies of autonomic
      nervous system function are usually the most productive direction in which to
      proceed. In patients with structural heart disease, a functional assessment of
      the suspected structural disturbance (i.e., hemodynamic, angiographic, imaging as
      appropriate) and evaluation for susceptibility to symptomatic arrhythmias by
      monitoring or conventional electrophysiologic testing is appropriate. Autonomic
      function testing should follow if the diagnosis remains unclear. In only a few
      instances should specialized neurologic studies be undertaken as an initial step.
      The ultimate objective is always to obtain a sufficiently strong correlation
      between syncopal symptoms and detected abnormalities to feel confident in the
      diagnosis, permit an accurate assessment of prognosis, and develop an appropriate
      treatment plan.

PMID- 9164709
TI  - Syncope. A neurologist's viewpoint.
AB  - Syncope is caused by a global reversible reduction of blood flow to the brain.
      Three hemodynamic abnormalities can cause syncope: (1) a fall in systemic blood
      pressure because of ineffective control of peripheral vascular resistance, (2) an
      acute decrease in cardiac output, and (3) an acute increase in cerebrovascular
      resistance. Complicating the differential diagnosis of syncope are other causes
      of loss of consciousness, such as seizures, metabolic disorders, and psychiatric
      disorders, which may simulate syncope.

PMID- 9164710
TI  - Value and limitations of noninvasive assessment of syncope.
AB  - The noninvasive assessment of patients who present with syncope is based on a
      thorough, complete history and physical examination. The history requires close
      attention to precipitating events and the description of the spell. Often,
      patients are poor historians with regard to symptoms leading up to and following
      the episode of syncope. Therefore, it is important to interview individuals who
      observed the spell to improve the accuracy of the history and sort out whether or
      not the spell was due to cardiogenic syncope, vasodepressor syncope, or a
      neurologic disorder. Carotid sinus massage is a useful procedure that can be
      performed during the routine physical examination, identifying patients who are
      at increased risk for carotid sinus syncope because of hypersensitivity of the
      carotid sinus. The clinician must be careful to attribute the clinical syncope to
      carotid sinus hypersensitivity only when the spell induced at the time of carotid
      massage reproduces the clinical spell. Routine laboratory tests are commonly
      performed, although the blood tests rarely yield information to confirm the cause
      of syncope. The routine ECG is often helpful identifying abnormalities of rhythm,
      conduction, or morphology that give a clue as to the cause for the patient's
      syncope. The most helpful aspect of ECG recording is to obtain a recording during
      an episode of syncope when exact correlation can be made between the ECG findings
      and the patient's symptoms. Recording the ECG during the spell can be achieved
      using 24-hour ambulatory monitoring, an event recorder, or a memory loop
      recorder. Twenty-four-hour ambulatory monitoring is useful in patients who have
      frequent spells that would be expected to be recorded during 1 or 2 days of
      monitoring. These individuals need to have a non-life-threatening spell and
      therefore be safe to evaluate as an outpatient. The event recorder and loop
      memory recorder have proved extremely helpful in evaluating spells that occur too
      infrequently to be recorded by 24-hour or 48-hour ambulatory monitoring. The
      nature of these recording devices does require that the patient or a companion be
      able to activate the monitor at the time of symptoms. If a patient experiences
      syncope but is unable to activate the device, the important information as to
      what the rhythm was doing at the time of symptoms is lost. The implantable loop
      recorder should prove to be uniquely advantageous by allowing extended ECG
      recording with the device activated by the patient or companion recording 20
      minutes before and 4 minutes after device activation. Signal-averaged
      electrocardiography is most helpful in assessing patients with ischemic heart
      disease with a substrate capable of supporting a reentrant ventricular
      arrhythmia. This test should be used in combination with other historical or
      laboratory predictors of arrhythmic events such as history of myocardial
      infarction or abnormal ventricular function assessed by echocardiography. In this
      setting, the signal-averaged ECG helps to identify patients at increased risk for
      ventricular tachycardia as the cause of syncope who thus may benefit from
      electrophysiologic testing.

PMID- 9164711
TI  - Value and limitations of electrophysical testing for syncope.
AB  - Syncope is by definition a transient event, and its cause has usually resolved by
      the time the patient is examined. Electrophysiologic testing provides a method
      for assessing a patient's risk for future arrhythmias based on the known
      sensitivity and specificity of the analyses of sinus node function,
      atrioventricular conduction, and responses to programmed atrial and ventricular
      stimulation. Interpretation of these data must always be made in the context of
      the patient's total clinical situation.

PMID- 9164712
TI  - Pathophysiologic basis for vasodepressor syncope.
AB  - The current knowledge regarding the pathophysiologic basis of the vasodepressor
      response was reviewed. The balance of evidence indicates that the mechanoreceptor
      hypothesis seems unlikely to be the sole afferent alteration that leads to the
      vasodepressor response. Alternative afferent mechanisms should include
      neurohumoral mediated sympathoinhibition triggered by opioid mechanisms as well
      as impaired endothelial and NO responses to orthostatic stress in susceptible
      individuals. It is possible that impaired cardiovagal and sympathetic outflow
      control of arterial baroreceptors is enhanced by the aforementioned mechanisms.
      The role of central sympathoinhibition and vagal excitation triggered directly
      from pathways within the temporal lobe or triggered by alterations in regional
      cerebral blood flow should be considered as potential alternative mechanisms.
      Efferent autonomic outflow during vasodepressor syncope include sympathetic
      neural outflow withdrawal in addition to activation of parasympathetic outflow to
      the heart and abdominal viscera. Further human research is needed to understand
      the underlying mechanisms that result in the described neural and vascular
      responses.

PMID- 9164713
TI  - Vasodepressor syncope. Diagnosis and management.
AB  - Vasodepressor syncope is a common medical problem that can be diagnosed through
      an accurate history and upright tilt testing. In most cases, patients experience
      a striking decrease in syncopal episodes following a tilt test, and long-term
      therapy is not necessary. In the rare patient who experiences no prodrome and
      continues to experience injury-causing syncope, empiric therapy with drugs or
      dual-chamber pacing has to be considered despite the lack of controlled trials
      establishing the efficacy of such therapies.

PMID- 9164714
TI  - Dysautonomic and reflex syncope syndromes.
AB  - Both dysautonomic and reflex syncope are common problems that, although related
      to neurocardiogenic syncope, are somewhat distinct entities. Proper diagnosis and
      management require an adequate knowledge of these disorders. Further
      investigations will continue to advance knowledge of these various disorders of
      orthostatic control.

PMID- 9164715
TI  - Psychiatric illness and syncope.
AB  - Studies have reported a high prevalence of psychiatric illness in patients with
      syncope, particularly among those with syncope of unknown etiology. Although
      mortality rates for patients with syncope and psychiatric disorders tend to be
      lower than for patients with cardiac cause for syncope, treatment of these
      psychiatric illnesses appears to result in lower rates of recurrence of the
      symptoms. The authors recommend an assessment for psychiatric illness in those
      patients in whom the initial evaluation does not suggest an organic cause for
      syncope. Further studies are needed to elucidate the pathophysiologic mechanisms
      for syncope and the effects of treatment of psychiatric illness on recurrence of
      syncope.

PMID- 9164716
TI  - Syncope in the pediatric patient.
AB  - Syncope in the pediatric patient is a common and usually benign event that
      frequently causes concern and anxiety. This article describes three general
      categories of syncope in children and adolescents: cardiac, noncardiac, and
      neurocardiogenic. The discussion includes specific pediatric issues and
      dissimilarities when compared to adult patients with syncope. In addition, a
      focused approach to the diagnostic evaluation of syncope in childhood is
      described.

PMID- 9164717
TI  - Syncope in the elderly.
AB  - Age-related physiologic changes and disease-related abnormalities predispose
      older adults to syncope. It is important to know the physiologic changes that
      occur with normal aging to understand better their interaction with disease
      processes and to facilitate better evaluation and treatment of syncope when it
      occurs. Attention to situational stresses, such as posture changes, meals, or
      medications, is also likely to increase the diagnostic yield and improve
      therapeutic strategies that can reduce morbidity and potential mortality of
      recurrent episodes. Therapy should be directed toward minimizing multiple factors
      that contribute to syncope, avoiding iatrogenic medication effects, and treating
      specific contributory diseases.

PMID- 9164718
TI  - Recurrent syncope. Experience with an implantable loop recorder.
AB  - The cause of recurrent syncope is often difficult to determine when initial
      laboratory investigations are negative. Advances in implantable monitoring
      technology permit long-term monitoring of the electrocardiogram in patients with
      recurrent undiagnosed syncope. A pilot device implanted in the left pectoral
      region established the cardiac rhythm during syncope in all 20 of 24 patients who
      developed syncope during follow-up. The cause was arrhythmic in 10 and
      nonarrhythmic in 10. Therapy resulted in resolution of symptoms in 17 of 20
      patients. The implantable loop recorder is a promising diagnostic tool for
      investigation of syncope.

PMID- 9164719
TI  - Driving issues related to arrhythmic syncope.
AB  - The safety of driving in patients with cardiac arrhythmias is a common concern.
      Although the risk of driving in these patients cannot be reduced to zero,
      available data and expert consensus suggest that most patients with arrhythmias
      can return to driving with a relatively low risk of harm to themselves and
      others, that is, a risk within the limits deemed acceptable by society. Specific
      recommendations for allowing patients with various cardiac rhythm abnormalities
      to drive are reviewed in detail.

PMID- 9164766
TI  - Health care utilization and cost among children with asthma who were enrolled in
      a health maintenance organization.
AB  - OBJECTIVE: To measure the impact of asthma on the use and cost of health care by
      children in a managed care organization. DESIGN: Population-based historical
      cohort study. SETTING: A medium-sized staff model health maintenance organization
      in western Washington state. SUBJECTS: All 71 818 children, between age 1 to 17
      years, who were enrolled and used services during 1992. OUTCOME MEASURES:
      Children were identified with one or more asthma diagnoses during 1992 using
      automated encounter data. Nonurgent outpatient visits, pharmacy fills, urgent
      care visits, and hospital days, as well as associated costs were measured. All
      services were categorized as asthma care or nonasthma care. Multivariate
      regression analysis was used to compute marginal cost for asthma (difference in
      total cost between children with asthma and other children using services,
      adjusted for covariates). RESULTS: Treated prevalence of asthma was 4.9%.
      Children with asthma incurred 88% more costs ($1060.32 vs $563. 81/yr), filled
      2.77 times as many prescriptions (11.59 vs 4.19/yr), made 65% more nonurgent
      outpatient visits (5.75 vs 3.48/yr), and had twice as many inpatient days (.23 vs
      .11/yr) compared with the general population of children using services. Asthma
      care represented 37% of all health care received by children with asthma, while
      the remaining 63% were for nonasthma services. Almost two-thirds of asthma
      related costs were attributable to nonurgent outpatient care and prescriptions;
      only one third was attributable to urgent care and hospitalizations. Controlling
      for age, sex, and comorbidities, the marginal cost of asthma was $615.17/yr (95%
      confidence interval $502.73, $727.61), which includes asthma as well as nonasthma
      services. This marginal cost represents 58% of all health care costs for children
      with asthma. CONCLUSIONS: Children with asthma use significantly more health
      services (and incur significantly more costs) than other children using services,
      attributable largely to asthma care. The majority of all health care costs for
      children with asthma were for nonasthma services. Urgent care visits and
      hospitalizations are less important components of asthma costs in this managed
      care organization than has been found in other national studies.

PMID- 9164767
TI  - Vaccine Safety Datalink project: a new tool for improving vaccine safety
      monitoring in the United States. The Vaccine Safety Datalink Team.
AB  - OBJECTIVE: To fill the large "gaps and limitations" in current scientific
      knowledge of rare vaccine adverse events identified in recent reviews of the
      Institute of Medicine. METHODS: Computerized information on immunization, medical
      outcomes, and potential confounders on more than 500 000 children 0 to 6 years of
      age is linked annually at several health maintenance organizations to create a
      large cohort for multiple epidemiologic studies of vaccine safety. RESULTS:
      Analysis of 3 years of follow-up data shows that 549 488 doses of diphtheria
      tetanus-pertussis (DTP) and 310 618 doses of measles-mumps-rubella (MMR) vaccines
      have been administered to children in the study cohort. Analyses for associations
      between vaccines and 34 medical outcomes are underway. Screening of automated
      data shows that seizures are associated with receipt of DTP on the same day
      (relative risk [RR], 2.1; 95% confidence interval [CI], 1.1 to 4.0) and 8 to 14
      days after receipt of MMR (RR, 3.0; 95% CI, 2.1 to 4.2). The diversity of
      vaccination exposures in this large cohort permits us to show that an apparent
      association of seizures 8 to 14 days after Haemophilus influenzae type b vaccine
      (RR, 1.6; 95% CI, 1.2 to 2.1) was attributable to confounding by simultaneous MMR
      vaccination; the association disappears with appropriate adjustment (RR, 1.0; 95%
      CI, 0.7 to 1.4). CONCLUSION: Preliminary design, data collection, and analytic
      capability of the Vaccine Safety Datalink project has been validated by
      replication of previous known associations between seizures and DTP and MMR
      vaccines. The diversity in vaccine administration schedules permits potential
      disentangling of effects of simultaneous and combined vaccinations. The project
      provides a model of public health-managed care collaborations in addition to an
      excellent infrastructure for safety and other studies of vaccines.

PMID- 9164768
TI  - Socioeconomic variation in discretionary and mandatory hospitalization of
      infants: an ecologic analysis.
AB  - OBJECTIVES: To examine geographic variation in rates of infant hospitalization
      for diagnoses classified by type of hospitalization decision in Monroe County
      (Rochester), New York. METHODS: Study design was cross-sectional and ecologic.
      International Classification of Diseases (ICD) codes were used to categorize all
      7883 hospitalizations for infants (age, <24 months) beyond the newborn period
      between 1985 and 1991. Postal zip codes defined socioeconomic areas as inner
      city, other urban, and suburban for the population at risk. In 1990, inner-city
      infants included 62% black and 65% Medicaid-covered infants, whereas suburban
      infants included 3% black and 6% covered by Medicaid. Hospitalization rates were
      compared among the three socioeconomic areas. RESULTS: Overall hospitalization
      rate was 50.3 per 1000 child years. Admissions classified as discretionary
      accounted for 59% of these, followed by those classified as mandatory, 18%;
      sometime (congenital heart disease, cleft palate), 15%; discretionary surgery
      (inguinal hernia, tonsillectomy/adenoidectomy), 6%; and unlikely to need
      admission, 2%. A stepwise, socioeconomic gradient in hospitalization was found,
      with rates of 38.1, 51.3, and 82.9 per 1000 child-years, respectively, for
      suburban, other urban, and inner-city areas. Rates for discretionary, unlikely,
      and mandatory admissions followed this gradient. Using the odds for
      hospitalization of suburban infants as the base odds, the odds ratio for
      discretionary hospitalization for inner-city infants was 2.88 (95% confidence
      interval [CI], 2.69 to 3. 08) and that for mandatory hospitalization was 2.20
      (95% CI, 1.94 to 2.49). In multiple regression analysis, low education level of
      mothers explained 81% of the variance in discretionary hospitalization rate.
      Although the per capita rate of hospital care of inner-city infants was more than
      twofold greater than that for suburban infants, potential for reducing this
      difference is suggested by the fact that discretionary admissions accounted for
      78. 9% of this difference, whereas mandatory admissions accounted for 17. 7% of
      the difference. CONCLUSION: The hospitalization rate for inner-city infants is
      much greater than that for suburban infants. A substantial portion of the
      difference, namely that attributable to mandatory admissions, reflected higher
      rates of serious illness. Differences attributable to discretionary admissions
      may reflect higher rates of serious illness to some extent, but also appear to
      reflect less effective health services to a substantial degree.

PMID- 9164769
TI  - Maternal and perinatal risk factors for later delinquency.
AB  - BACKGROUND: The early identification of risk factors for juvenile offending is
      one important step in preventing youth violence and offending. This cohort study
      examined whether perinatal circumstances predicted offending during adolescence.
      METHODS: Washington State birth certificates from 1974 to 1975 were linked to
      juvenile justice data to identify all individuals adjudicated between 10 and 17
      years of age. Thirteen thousand five hundred seventy-three offenders were
      compared with a sample of 38 387 nonoffenders matched on gender and birth order.
      RESULTS: Both male and female children of mothers who were teenagers at the
      child's birth or at her first birth, or who were born to unmarried mothers, had
      significantly increased risk for any juvenile offending, and for being
      adjudicated for five or more crimes (chronic offending). Males born to unmarried
      mothers under 18 years old had an 11-fold increased risk of chronic offending
      compared with males born to married mothers >/=20 years old. Low birth weight and
      preterm gestational age carried no increased risk for juvenile offending.
      CONCLUSIONS: Birth to teenage or unmarried mothers are strongly associated with
      later risk of juvenile delinquency. Although there are multiple, interrelated
      risk factors for juvenile delinquency, prevention of births to teenage and/or
      unmarried mothers may help to prevent subsequent juvenile delinquency.

PMID- 9164770
TI  - The associations of suicide attempts in adolescents.
AB  - OBJECTIVE: Suicide completion has increased in the United States among 15- to 24
      year-olds from 4.5 per 100 000 (1950) to 13.2 per 100 000 (1990). Suicide
      attempts have been found to be associated with depression, substance use, overall
      number of life stressors, gender, and impulsive behaviors. We hypothesized that
      suicide attempt is associated with many other health risk behaviors. DESIGN: To
      evaluate this hypothesis, we analyzed the data from the 1993 Massachusetts Youth
      Risk Behavior Survey from a representative sample of students in grades 9 through
      12 in public and private high schools. We examined the relationships between ever
      attempting suicide and engaging in other health risk or problem behaviors (eg,
      sexual activity, substance use, violence, and seat belt nonuse). RESULTS: The
      3054 students were distributed among the 9th to 12th grades; 50.7% were female,
      77.7% white, 6.7% black, 5.9% Hispanic, 4. 6% Asian, .8% Native American, and
      4.4% other; and the mean age was 16 +/- 1.2 years. Based on logistic regression
      analysis, ever attempting suicide was associated with physical fights in the past
      12 months (odds ratio [OR] = 1.3[95% confidence interval (CI), 1. 22-1.44]),
      regular cigarette use in the past 30 days (2.0[1.41-2. 97]), female gender
      (3.2[2.21-4.71]), lack of seat belt use (1.3[1. 21-1.34]), gun carrying in the
      past 30 days (1.4[1.12-1.70]), substance use before last sexual activity
      (1.4[1.09-1.84]), Native American or other (2.4[1.21-4.71]), and lifetime use of
      other drugs (1.2[1.04-1.40]). The full model correctly assigned 92% of the youth.
      There were small differences in models for males, females, and sexually active
      youth. Same gender sexual experiences for sexually active youth did not
      significantly improve the model (partial r = .0, OR = .87 [95% CI, .33-2.30]) and
      fewer (88%) of the youth were correctly assigned by the model. CONCLUSIONS: Ever
      attempting suicide is associated with other problem behaviors. This research
      proposes an empirical model of the relationship between suicide attempts and
      other health risk behaviors. Identifying which adolescents are at risk for
      suicide attempts from the presence of accompanying risk behaviors will help
      clinicians to evaluate suicide risk when other problem behaviors are identified,
      thus enabling the design of possible prevention strategies.

PMID- 9164771
TI  - Clinicopathological correlations in postasphyxial organ damage: a donor organ
      perspective.
AB  - OBJECTIVES: 1) To assess pathology in the heart, kidneys, lungs, liver, and
      intestine in babies dying of postasphyxial hypoxic ischemic encephalopathy (HIE),
      and their suitability for organ transplantation. 2) To analyze the correlation
      between in vivo clinical markers of collateral organ damage and autopsy findings.
      STUDY DESIGN: Retrospective cohort study of 58 infants who died of postasphyxial
      HIE and had autopsies during 1985 to 1994. Collateral organ damage was evaluated
      clinically and pathologically, and the results compared. RESULTS: Severe
      pathological changes were observed in 6% to 62% of the five organs studied; 59%
      of the four major organs had either minor or no pathology. The sensitivity of the
      clinical predictors ranged from 69% to 100%, and specificity from 50% to 97%.
      CONCLUSIONS: The organs of newborns dying of severe HIE may be suitable for use
      as donor organs; predictions of their suitability were most accurate for liver,
      kidney, and lungs, and least accurate for the heart.

PMID- 9164772
TI  - Ten-year clinical, developmental, and intellectual follow-up of children with
      congenital cytomegalovirus infection without neurologic symptoms at one year of
      age.
AB  - OBJECTIVE: This study was undertaken to ascertain whether children with
      congenital cytomegalovirus (CMV) infection at birth, but without neurologic
      symptoms at 1 year of age, differed in somatic, neurologic, developmental, or
      intellectual status from matched control children at long-term follow-up.
      MATERIAL AND METHODS: Congenital CMV infection, as demonstrated by isolation of
      the virus within the first week of life, was diagnosed in 44 (0.5%) of 9806
      infants. From this basic CMV-infected population, children who developed
      neurologic disturbances including sensorineural deafness before 1 year of age
      were excluded (n = 7), as were those unwilling to participate (n = 2).
      Congenitally infected infants (n = 35) and matched control infants (n = 53) were
      followed up clinically and neurologically. At 21 months, development was assessed
      with the Griffiths' Developmental Scale and at 7 years of age neurologic status
      was assessed with the Stott test and intellectual development with the Wechsler
      Intelligence Scale for Children. RESULTS: As reported previously, 18% (8/44) of
      the CMV-infected infants manifested symptoms at birth, as compared to 8% (4/53)
      in the control group. In the congenital CMV group 7% (2/30) children tested had
      abnormal Stott test results, as compared to 2% (1/43) in the control group.
      Thirty-two CMV-infected and 51 control group children were assessed with the
      Griffiths' scale at 21 months of age. The two groups did not differ
      significantly, either in mean scores (6.3 +/- 2.3 vs 6.1 +/- 1.9) or in the
      proportion of children with scores below normal (19% [6/32] vs 16% [8/51]).
      Twenty-five CMV-infected and 41 control group children were assessed with the
      Wechsler Intelligence Scale for Children at 7 years of age (median 86 months;
      range, 82 to 90 and 82 to 91, respectively). The two groups did not differ
      significantly, either in mean scores (5.8 +/- 2.0 vs 6.4 +/- 1.6) or in the
      proportion of children with scores below normal (12% [3/25] vs 5% [2/41]).
      CONCLUSION: Children with congenital CMV infection are unlikely to be at an
      increased risk of subsequent neurodevelopmental or intellectual impairment if
      they show normal development at 12 months of age.

PMID- 9164773
TI  - The utility of body mass index as a measure of body fatness in children and
      adolescents: differences by race and gender.
AB  - OBJECTIVE: To evaluate whether body mass index (BMI) is a representative
      equivalent measure of body fatness independent of age, race, gender, sexual
      maturation, and distribution of fat in children and adolescents. STUDY DESIGN:
      Cross-sectional study of 192 healthy subjects (100 boys and 92 girls, 103 white
      and 89 black) age 7 to 17 years. Methods. Height and weight were measured in the
      standard fashion, and BMI (kg/m) was calculated from these values. Fat mass and
      percent body fat were determined using dual-energy x-ray absorptiometry. Sexual
      maturation was evaluated by physical assessment. Distribution of fat was
      determined by the waist:hip ratio. RESULTS: There were no significant differences
      by gender and ethnic group for any of the demographic or anthropometric
      variables, except waist:hip ratio, which was higher in white compared with black
      boys. BMI was significantly and positively correlated with age, stage of
      maturation, and all of the anthropometric variables in each race-sex group. The
      correlation of maturation stage with BMI was stronger than the correlation
      between age and BMI. A multiple regression analysis showed that BMI, gender,
      race, sexual maturation, and distribution of fat were all significant independent
      correlates of the percent body fat (multiple R = .77). The percent body fat-BMI
      relationship was dependent on the stage of sexual maturation, gender (for an
      equivalent BMI, girls have greater amounts of body fat than boys), race (for
      equivalent BMI, whites have higher body fat than blacks), and waist:hip ratio
      (for equivalent BMI, those with central obesity have greater body fatness than
      those with peripheral obesity). CONCLUSION: BMI is not an equivalent measure of
      the percent body fat for each race-sex group. When BMI is used as a measure of
      body fatness in a research or clinical setting, particularly when comparisons are
      made across race and gender, it may be important to consider the maturation
      stage, race, gender, and distribution of body fat in the interpretation of the
      results.

PMID- 9164774
TI  - Impact of zinc supplementation on morbidity from diarrhea and respiratory
      infections among rural Guatemalan children.
AB  - OBJECTIVE: A community-based, randomized, double-blind intervention trial was
      conducted to measure the impact of zinc supplementation on young Guatemalan
      children's morbidity from diarrhea and respiratory infections. METHODS: Children
      aged 6 to 9 months were randomly assigned to receive 4 mL of a beverage
      containing 10 mg of zinc (as zinc sulfate) daily (7 d/wk) for 7 months (n = 45)
      or a placebo (n = 44). Morbidity data were collected daily. Diagnoses of
      diarrhea, fever, and anorexia were based on mothers' definitions. Respiratory
      infections were defined as the presence of at least two of the following
      symptoms: runny nose, cough, wheezing, difficulty breathing, or fever. RESULTS:
      High rates of diarrhea and respiratory infections were reported. Children from
      the placebo group had a 20% episodic prevalence of diarrhea, with 8 episodes/100
      d, and a 7% episodic prevalence of respiratory infections, with 3 episodes/100 d.
      The median incidence of diarrhea among children who received zinc supplementation
      was reduced by 22% (Wilcoxon rank test), with larger reductions among boys and
      among children with weight-for-length at baseline lower than the median of the
      sample (39% reductions in both subgroups). Zinc supplementation also produced a
      67% reduction in the percentage of children who had one or more episodes of
      persistent diarrhea (chi2 test). No significant effects were found on the
      episodic prevalence of diarrhea, the number of days per episode, or the episodic
      prevalence or incidence of respiratory infections. CONCLUSIONS: The large impact
      of zinc supplementation on diarrhea incidence suggests that young, rural
      Guatemalan children may be zinc deficient and that zinc supplementation may be an
      effective intervention to improve their health and growth.

PMID- 9164775
TI  - Effect of diuretics on urinary oxalate, calcium, and sodium excretion in very low
      birth weight infants.
AB  - OBJECTIVE: To study the effect of diuretic drugs on urinary oxalate excretion in
      premature infants, and to examine the relationship between urinary calcium and
      sodium excretion in premature infants. METHODOLOGY: We measured urinary oxalate,
      calcium, and sodium excretion in 32 premature infants at approximately 34 weeks
      gestational age. Seven infants were receiving furosemide, 5 infants were
      receiving thiazide, 8 infants were receiving furosemide plus thiazide, and 12
      infants who were not receiving diuretics served as controls. RESULTS: Urinary
      oxalate to creatinine ratios in infants receiving furosemide (0.48 +/- .26),
      thiazide (0.54 +/- .20), furosemide plus thiazide (0.44 +/- .19), and control
      infants (0.51 +/- .43) were similar by analysis of variance (ANOVA). Data
      expressed as oxalate concentration gave similar results. Urinary calcium to
      creatinine ratios in infants receiving furosemide (0.81 +/- .30), thiazide (0.54
      +/- .25), furosemide plus thiazide (0.75 +/- .49), and control infants (0.37 +/-
      .25) were similar by ANOVA. The urinary calcium concentration in infants
      receiving furosemide plus thiazide (0.085 +/- 0.042 mg/mL) was different from
      control infants (0.044 +/- .023) by ANOVA and Student-Newman-Keuls test. Urinary
      calcium to creatinine ratio was correlated with sodium to creatinine ratio (r =
      .751). CONCLUSION: Urinary oxalate excretion in premature infants is not affected
      by diuretic drugs. Urinary sodium and calcium excretion are closely linked in
      sodium supplemented premature infants receiving diuretics. The calciuric effect
      of furosemide is not decreased by the addition of thiazide in premature infants
      receiving sodium supplements.

PMID- 9164776
TI  - Newborn screening for cystic fibrosis in Wisconsin: comparison of biochemical and
      molecular methods.
AB  - OBJECTIVES: To evaluate neonatal screening for cystic fibrosis (CF), including
      study of the screening procedures and characteristics of false-positive infants,
      over the past 10 years in Wisconsin. An important objective evolving from the
      original design has been to compare use of a single-tier immunoreactive
      trypsinogen (IRT) screening method with that of a two-tier method using IRT and
      analyses of samples for the most common cystic fibrosis transmembrane regulator
      (CFTR) (DeltaF508) mutation. We also examined the benefit of including up to 10
      additional CFTR mutations in the screening protocol. METHODS: From 1985 to 1994,
      using either the IRT or IRT/DNA protocol, 220 862 and 104 308 neonates,
      respectively, were screened for CF. For the IRT protocol, neonates with an IRT
      >/=180 ng/mL were considered positive, and the standard sweat chloride test was
      administered to determine CF status. For the IRT/DNA protocol, samples from the
      original dried-blood specimen on the Guthrie card of neonates with an IRT >/=110
      ng/mL were tested for the presence of the DeltaF508 CFTR allele, and if the DNA
      test revealed one or two DeltaF508 alleles, a sweat test was obtained. RESULTS:
      Both screening procedures had very high specificity. The sensitivity tended to be
      higher with the IRT/DNA protocol, but the differences were not statistically
      significant. The positive predictive value of the IRT/DNA screening protocol was
      15.2% compared with 6.4% if the same samples had been screened by the IRT method.
      Assessment of the false-positive IRT/DNA population revealed that the two-tier
      method eliminates the disproportionate number of infants with low Apgar scores
      and also the high prevalence of African-Americans identified previously in our
      study of newborns with high IRT levels. We found that 55% of DNA-positive CF
      infants were homozygous for DeltaF508 and 40% had one DeltaF508 allele. Adding
      analyses for 10 more CFTR mutations has only a small effect on the sensitivity
      but is likely to add significantly to the cost of screening. CONCLUSIONS:
      Advantages of the IRT/DNA protocol over IRT analysis include improved positive
      predictive value, reduction of false-positive infants, and more rapid diagnosis
      with elimination of recall specimens.

PMID- 9164777
TI  - Milk-induced hypoalgesia in human newborns.
AB  - OBJECTIVE: To determine whether milk and its components reduce crying in newborns
      during and after blood collection for phenylketonuria evaluation. METHODOLOGY:
      Seventy-two normal newborns ingested 2 mL of milk (Similac), Ross Special
      Formula, fat, protein, lactose, sucrose, or water for the 2 minutes preceding
      blood collection via heel lance. Crying duration during and for the 3 minutes
      after the procedure was determined by scorers who were blind to the ingestive
      substance. RESULTS: Sucrose and Similac each reduced crying during the blood
      collection procedure. Sucrose, fat, protein, and Ross Special Formula were
      effective during the 3-minute recovery period. Neither water nor lactose were
      effective during or after blood collection. CONCLUSION: Milk and some of its
      components are antinociceptive in human newborns. Based on previous studies,
      reduced crying during and after painful stimulation may be mediated through
      endogenous opioids. These findings are of potential clinical significance:
      natural protective mechanisms, normally engaged during suckling, may safely and
      noninvasively be activated to reduce newborn crying to painful stimulation.

PMID- 9164778
TI  - An economic analysis of developmental detection methods.
AB  - OBJECTIVE: To assess the costs and benefits of various approaches to early
      detection of developmental disabilities. DESIGN: Cost-benefit analyses based on
      data from previously published studies of developmental screening tests. SETTING:
      General pediatric practices and day care centers. PATIENTS AND OTHER
      PARTICIPANTS: A total of 247 parents and their 0- to 6-year-old children-103 from
      day care centers and 144 from pediatric practices. MAIN OUTCOME MEASURES:
      Licensed psychological examiners administered a screening test of parents'
      concerns about children's development and one or two direct screening tests: the
      Denver-II and/or the Battelle Developmental Inventory Screening Test. For the day
      care sample, examiners also administered to each child measures of intelligence,
      adaptive behavior, and language. In the pediatric sample, children were
      administered additional assessments. At the same time, diagnostic measures were
      administered to a randomly selected subsample to make determinations about
      developmental status. Each screening method was evaluated for its short-term
      costs (administration, interpretation, diagnosis, and treatment) and long-term
      benefits (impact of early intervention on adult functioning as inferred from
      longitudinal studies by other researchers). RESULTS: When the long-term costs and
      benefits were considered, none of the approaches emerged as markedly superior to
      another. When viewing the short-term costs, the various screening approaches
      differed markedly. The use of parents' concerns was by far the least costly for
      physicians to administer and interpret. CONCLUSION: Physicians can incur
      tremendous expenses when attempting to detect children with developmental
      problems. Although the benefits of early detection and intervention are
      substantial, physicians are not well-compensated for providing a critical service
      to society. Health policymakers and third-party payers must reconsider their
      minimal investment in early detection by health care providers. Nevertheless, our
      findings have encouraging implications for practice, because the use of parents'
      concerns as a screening technique offers substantial savings over and above other
      methods.

PMID- 9164779
TI  - Intrapartum hypoxic-ischemic cerebral injury and subsequent cerebral palsy:
      medicolegal issues.

PMID- 9164780
TI  - Prevention of early-onset neonatal group B streptococcal disease.

PMID- 9164781
TI  - The outcomes of very low birth weight infants: are we asking the right questions?

PMID- 9164782
TI  - The status of pediatric practice guidelines.

PMID- 9164783
TI  - Children in diverse family constellations. Committee on Psychosocial Aspects of
      Child and Family Health of the American Academy of Pediatrics.

PMID- 9164784
TI  - Toward simple but safe management of osteomyelitis.

PMID- 9164785
TI  - The Food and Drug Administration's rule on tobacco: blending science and Law.

PMID- 9164786
TI  - Socioeconomic status, health, and health systems.

PMID- 9164787
TI  - The ouchless place: no pain, children's gain.

PMID- 9164788
TI  - Recurrent myoglobinuria as a presenting manifestation of very long chain acyl
      coenzyme A dehydrogenase deficiency.

PMID- 9164789
TI  - Colonic sunflower seed bezoar.

PMID- 9164790
TI  - Clinical varicella following varicella vaccination: don't be fooled.

PMID- 9164791
TI  - Cavitary legionellosis in two immunocompetent infants.

PMID- 9164792
TI  - Medication for children with attention disorders.

PMID- 9164794
TI  - The apnea/SIDS debate.

PMID- 9164793
TI  - Vocal cord dysfunction mimicking exercise-induced bronchospasm in adolescents.

PMID- 9164795
TI  - Intubation rates in extremely low birth weight infants.

PMID- 9164797
TI  - Solar protection of children at the beach.
AB  - BACKGROUND: Excessive sun exposure during childhood has been associated with
      subsequent development of skin cancers. Children have been advised to avoid sun
      exposure, use protective clothing, and apply sunscreen lotions, but how
      completely these recommendations are followed has not been studied. OBJECTIVE: To
      determine the extent of sun protection among children visiting lake beaches, the
      methods used, and the characteristics associated with more protection. DESIGN:
      Direct observations of children were linked with concurrent care giver/parent
      interviews. SUBJECTS/SETTING: A total of 871 children 2 to 9 years of age and
      their parents/care givers at freshwater beaches in 10 small New Hampshire towns
      during July and August 1995. OUTCOME MEASURES: Protection of the head, torso, and
      legs according to method used (hats, shirts, pants, sunscreen, or shade).
      RESULTS: Fifty-four percent of children were protected by at least one method for
      all three body surface regions, although 17% had no protection for any region.
      Sunscreen was used either alone or in combination with clothing for at least one
      region in 79%. Hats were used by 3%, shirts by 22%, and pants to the knee by 49%.
      Only 12% of observed children were in the shade. The region that was protected
      most often was the legs for boys (due to swim suit styles) followed by the torso
      for both sexes. The region most often unprotected was the legs for girls followed
      closely by the face for both boys and girls. Girls were significantly more likely
      to have no protection (31.2% female vs 7% male, chi2 83.3) due to better leg
      protection from swim trunks to the knees popular with boys. Full protection of
      all three regions was more common for children younger than 5 (odds ratio [OR] =
      1.8, 95% confidence interval, [CI] 1.3-2.5), for children perceived to usually or
      always burn (OR = 2.0, 95% CI 1.4-2.7), for children whose parents had more than
      a high school education (OR = 1.8, 95% CI 1.3-2.5), and if the parents indicated
      receiving sun protection information from a school or clinician during the
      previous year (OR = 1.7, 95% CI 1.2-2.3). Approximately 51.6% of parents recalled
      receiving childhood solar protection advice in the past year from either their
      physician, a nurse, or a school/day care setting. CONCLUSIONS: Sunscreen provided
      the most common form of solar protection. Hats and shade were used rarely, and
      shirts were also underused. Although the sun protection of these children
      visiting the beach was substantial, nearly half were still not fully protected.
      Clinician advice within the past year was associated with better protection.
      Clinicians could increase their influence by providing more specific counseling
      about how to achieve full protection. Use of multiple methods of protection
      rather than just sunscreen and full protection rather than protection for just
      one or two body regions should be emphasized. It is helpful to remind families to
      protect the regions most frequently omitted from protection: girls' legs and
      boys' and girls' faces. Advice can be enhanced with patient education materials
      such as included in the "Slip" (on a shirt), "Slop" (on sunscreen), and "Slap"
      (on a hat) program developed in Australia and available through the American
      Cancer Society.

PMID- 9164798
TI  - Resource utilization among neonatologists in a university children's hospital.
AB  - OBJECTIVE: We studied factors affecting length of hospital stay and resulting
      hospital charges among patients managed by two separate groups of neonatologists
      in the same academic health science center. DESIGN: Retrospective analysis of
      clinical and financial data base information. METHODS: Neonatal intensive care
      was provided in the same acute care nursery in a large university children's
      hospital by: (1) neonatologists in a full-time academic division (group A) and
      (2) a group associated with a private managed care organization (group B).
      Clinical and financial parameters of all neonates admitted in fiscal year 1994
      were compared for the two provider groups. Stepwise regression analysis was used
      to evaluate factors influencing hospital charges and length of hospital stay
      (LOS) and to adjust for differences in clinical variables between the two groups.
      RESULTS: Group A physicians provided care for 340 infants, while 137 were treated
      by those of group B. Group A included older patients, more outborns, more level
      III patients, more sepsis, more intermittent positive pressure ventilation, and
      more patent ductus arteriosus. The incidence of transient tachypnea of the
      newborn was higher among group B patients. Hospital charges were primarily
      determined by LOS, which was similar for the two groups. When the data were
      corrected for differences in risk and patient acuity, however, a significant
      relationship between physician group and LOS was demonstrated, with LOS being an
      average of 7.8 days shorter for group A. A net reduction of $3 114 969 in
      hospital charges might have been realized had group A physicians provided care
      for all study patients. CONCLUSIONS: Hospital charges were determined by LOS. In
      this setting, academic neonatologists produced shorter LOS and comparable
      clinical outcomes, despite caring for a population at greater risk. The reduction
      in LOS could have resulted in more than $3.1 million in annualized savings had
      the academic group provided care for all of the study patients.

PMID- 9164799
TI  - Prevalence of retinal hemorrhages in pediatric patients after in-hospital
      cardiopulmonary resuscitation: a prospective study.
AB  - OBJECTIVE: Child abuse occurs in 1% of children in the United States every year;
      10% of the traumatic injuries suffered by children under 5 years old are
      nonaccidental, and 5% to 20% of these nonaccidental injuries are lethal. Rapid
      characterization of the injury as nonaccidental is of considerable benefit to
      child protection workers and police investigators seeking to safeguard the child
      care environment and apprehend and prosecute those who have committed the crime
      of child abuse. Physically abused children present with a variety of well
      described injuries that are usually easily identifiable. In some cases, however,
      particularly those involving children with the shaken baby syndrome, obvious
      signs of physical injury may not exist. Although external signs of such an injury
      are infrequent, the rapid acceleration-deceleration forces involved often cause
      subdural hematomas and retinal hemorrhages, hallmarks of the syndrome.
      Frequently, retinal hemorrhages may be the only presenting sign that child abuse
      has occurred. Complicating the interpretation of the finding of retinal
      hemorrhages is the belief by some physicians that retinal hemorrhages may be the
      result of chest compressions given during resuscitative efforts. The objective of
      this study is to determine the prevalence of retinal hemorrhages after inpatient
      cardiopulmonary resuscitation (CPR) in pediatric patients hospitalized for
      nontraumatic illnesses in an intensive care unit. DESIGN: Prospective clinical
      study. SETTING: Pediatric intensive care unit. PATIENTS: Forty-three pediatric
      patients receiving at least 1 minute of chest compressions as inpatients and
      surviving long enough for a retinal examination. Patients were excluded if they
      were admitted with evidence of trauma, documented retinal hemorrhages before the
      arrest, suspicion of child abuse, or diagnosis of near-drowning or seizures. All
      of the precipitating events leading to cardiopulmonary arrest occurred in our
      intensive care unit, eliminating the possibility of physical abuse as an
      etiology. INTERVENTIONS: None. MEASUREMENTS: Examination of the retina was
      performed by one of two pediatric ophthalmologists within 96 hours of CPR. The
      chart was reviewed for pertinent demographic information; the platelet count,
      prothrombin time, and partial thromboplastin time proximate to the CPR were
      recorded if they had been determined. RESULTS: A total of 43 pediatric patients
      hospitalized with nontraumatic illnesses survived 45 episodes of inpatient CPR.
      The mean age was 23 months (range, 1 month to 15.8 years), and 84% of the
      patients were under 2 years old. The majority of the patients (44%) were admitted
      to the intensive care unit after surgery for congenital heart disease, and
      another 21% were admitted for respiratory failure. The mean duration of chest
      compressions was 16.4 minutes +/- 17 minutes with 58% lasting between 1 and 10
      minutes. Five patients had chest compressions lasting >40 minutes, and two
      patients had open chest cardiac massage. All patients survived their
      resuscitative efforts. Ninety-three percent of patients had an elevated
      prothrombin time and/or partial thromboplastin time while 49% were
      thrombocytopenic. Sixty-two percent of the patients had low platelet counts and
      an elevated prothrombin time and/or partial thromboplastin time. Small punctate
      retinal hemorrhages were found in only one patient. CONCLUSIONS: Retinal
      hemorrhages are rarely found after chest compressions in pediatric patients with
      nontraumatic illnesses, and those retinal hemorrhages that are found appear to be
      different from the hemorrhages found in the shaken baby syndrome. Despite the
      small number of patients in this prospective study, we believe that these data
      support the idea that chest compressions do not result in retinal hemorrhages in
      children with a normal coagulation profile and platelet count. A larger number of
      patients should be evaluated in a prospective multi-institutional study to
      achieve statistical significance

PMID- 9164800
TI  - Universal newborn hearing screenings: a three-year experience.
AB  - OBJECTIVE: To perform hearing screenings on all newborns before hospital
      discharge, using auditory brainstem evoked responses with analysis of time, cost,
      and failure rates to evaluate and determine the screening practicality. METHOD:
      Over a 3-year period from January 1, 1993 to December 31, 1995, auditory
      brainstem evoked response screenings were performed on 15 749 infants born at
      Saint Barnabas Medical Center, Livingston, New Jersey, before their hospital
      discharge by certified/licensed audiologists. The auditory brainstem evoked
      response screenings were conducted using the Nicolet Compass Evoked Potential
      System. RESULTS: A 3-year experience of testing 15 749 infants proved to be a
      cost-effective program with costs less than $30.00/baby. To date, 46 babies have
      been identified with bilateral sensorineural hearing loss and 6 babies with
      unilateral sensorineural hearing loss. CONCLUSIONS: The universal newborn hearing
      screening program at Saint Barnabas Medical Center has proved to be effective,
      beneficial, and necessary for an institution with more than 5000 births,
      annually. Early identification of hearing loss has resulted in infants receiving
      early intervention, and the screening program has provided education and follow
      up services to both parents and physicians.

PMID- 9164801
TI  - A longitudinal analysis of infant morbidity and the extent of breastfeeding in
      the United States.
AB  - BACKGROUND: Studies on the health benefits of breastfeeding in developed
      countries have shown conflicting results. These studies often fail to account for
      confounding, reverse causality, and dose-response effects. We addressed these
      issues in analyzing longitudinal data to determine if breastfeeding protects US
      infants from developing diarrhea and ear infections. METHODS: Mothers
      participating in a mail panel provided information on their infants at ages 2, 3,
      4, 5, 6, and 7 months. Infants were classified as exclusively breastfed; high,
      middle, or low mixed breast- and formula-fed; or exclusively formula-fed.
      Diarrhea and ear infection diagnoses were based on mothers' reports. Infant age
      and gender; other liquid and solid intake; maternal education, occupation, and
      smoking; household size; family income; and day care use were adjusted for in the
      full models. RESULTS: The risk of developing either diarrhea or ear infection
      increased as the amount of breast milk an infant received decreased. In the full
      models, the risk for diarrhea remained significant only in infants who received
      no breast milk compared with those who received only breast milk (odds ratio =
      1.8); the risk for ear infection remained significant in the low mixed feeding
      group (odds ratio = 1.6) and among infants receiving no breast milk compared with
      those who received only breast milk (odds ratio = 1.7). CONCLUSIONS:
      Breastfeeding protects US infants against the development of diarrhea and ear
      infection. Breastfeeding does not have to be exclusive to confer this benefit. In
      fact, protection is afforded in a dose-response manner. The more breast milk an
      infant receives in the first 6 months of life, the less likely that he or she

PMID- 9164802
TI  - Parents' and physicians' views on antibiotics.
AB  - OBJECTIVE: To describe parents' opinions and concerns about antibiotics and to
      contrast these opinions with those of pediatricians. DESIGN: Parents were
      surveyed using an interviewer-administered questionnaire and pediatricians were
      mailed a self-administered questionnaire. RESULTS: Parents from two private
      practices (N = 300) were largely white (84%) and had completed college (81%). The
      parents from a community health center (N = 100) were mostly black (80%) and had
      not completed college (91%). Twenty-nine percent of parents were worried that
      their children were receiving too many antibiotics. Eighty-five percent believed
      there were problems with receiving too many antibiotics, with 55% mentioning
      resistance or immunity as concerns. Eighteen percent of parents had given their
      child an antibiotic at home before consulting a physician. Parents believed that
      antibiotics were always or sometimes required for ear infections (93%), throat
      infections (83%), colds (32%), cough (58%), and fever (58%). Fourteen percent of
      parents believed that their child had required an antibiotic when the doctor did
      not prescribe one, with clinic parents significantly more likely to report this
      issue (22%) than private practice parents (12%). Nine percent believed that their
      doctor had prescribed an antibiotic unnecessarily (private practice = 12%,
      community health center = 3%). Parents from the private practices were also more
      likely to report requesting a specific antibiotic (34%) in comparison with 19% of
      clinic parents. Sixty-one percent of the physician surveys were returned after
      two mailings and a follow-up phone call. The pediatricians had been in practice
      for a median of 12 years, seeing a median of 110 patients per week. Fifty-eight
      percent of pediatricians reported that some, many, or most of the parents in
      their practices were worried that their children were receiving too many
      antibiotics. Seventy-one percent indicated that four or more times during the
      previous month, a parent had requested an antibiotic when the physician believed
      it was unnecessary, and 35% said that at least occasionally they went along with
      these requests. Sixty-one percent reported that parents requested a different
      antibiotic from the one they were going to prescribe at least four times in the
      previous month, and 30% of pediatricians said that they agreed to parents'
      requests often or most of the time. CONCLUSIONS: Both the parent and the
      physician surveys suggest that parents are concerned about the overuse of
      antibiotics, but often request them when their physicians believe they are
      unnecessary. Parents often administer antibiotics without physician knowledge,
      and many parents have misconceptions about which illnesses warrant antibiotic
      therapy. Understanding parents' concerns and beliefs about antibiotics and the
      range of physician practice styles with respect to antibiotics may direct the
      development of intervention strategies to reduce the inappropriate use of oral
      antibiotics.

PMID- 9164803
TI  - Japanese experience with micropremies weighing less than 600 grams born between
      1984 to 1993.
AB  - The viability limit defined by the Japanese Eugenic Protection Act was amended
      from 24 to 22 completed weeks of gestation in 1991. To testify if the amendment
      is appropriate, we conducted a survey on the mortality and morbidity rates of
      infants less than 600 g born in Japan between 1984 to 1993. Questionnaires were
      mailed to 205 hospitals with neonatal intensive care units (NICUs) and 165 (80%)
      responded. Of 1655 infants <600 g birth weight and admitted to the NICUs included
      in this survey, 457 (28%) survived to hospital discharge. The survival rates of
      infants born <24 weeks and >==24 weeks of gestation were 17% (128/748) and 36%
      (329/903), respectively; and of infants <500 g and 500 to 599 g at birth were 16%
      (82/510) and 32% (375/1145), respectively. None of the infants <==20 weeks of
      gestational age and <==350 g at birth survived, but 4% (2/49), 12% (27/218), 21%
      (99/474), and 34% (131/381) born at 21, 22, 23, and 24 weeks of gestation
      survived, respectively. The majority (68%) died within 1 week after birth and
      only 10% died after the neonatal period. The main causes of death were: acute
      respiratory failure (33%), intraventricular hemorrhage (20%), infection (16%),
      and heart failure (10%). Of 457 survivors, 65% were free from handicaps. The
      incidence of mental retardation (DQ < 70), visual disturbance, and CP were 15%,
      14%, and 11%, respectively. Admission of micropremies to NICU increased markedly
      after the amendment of the Eugenic Protection Act, despite a marked decline in
      birth rate. The survival rate increased from 22% to 33% after generalized use of
      surfactant in 1988, but the handicap rate (35%) among survivors remained
      unchanged. The new viability limit of 22 complete weeks of gestation was
      feasible, since survival of less than 22 weeks was exceptional while survival of
      22 to 23 weeks was 18%.

PMID- 9164804
TI  - Vaginal gonococcal cultures in sexual abuse evaluations: evaluation of selective
      criteria for preteenaged girls.
AB  - OBJECTIVE: Accurate selective criteria could limit the number of vaginal cultures
      for Neisseria gonorrhoeae performed on preteenaged girls as part of their sexual
      abuse evaluations. This study was performed to determine whether the published
      selective criteria by the American Academy of Pediatrics (AAP) Committee on Child
      Abuse and Neglect and by Siegel et al would have accurately detected all cases of
      vaginal gonococcal infections in our large study population. METHODS: We
      prospectively studied girls, ages 1 to 12 years, who were referred to our Child
      Sexual Abuse Team (CSAT) at Wake Medical Center in Raleigh, NC, between July 1,
      1976 to July 1, 1996, for sexual abuse evaluations which were performed using a
      protocol that included collecting historical information, a sexual abuse
      interview, and a detailed genital examination which included a vaginal culture
      for N gonorrhoeae. RESULTS: Our study population consisted of 2898 girls of whom
      2731 (94%) had vaginal cultures successfully performed for N gonorrhoeae. There
      were 84 girls with vaginal gonococcal infections, 80 of whom had a vaginal
      discharge. The four girls without a vaginal discharge included two with a history
      of having vaginal intercourse with an alleged perpetrator with gonorrhea, one
      with N gonorrhoeae isolated from a urine culture, and one whose preteenaged
      sister had gonorrhea. All of the 84 girls would have been identified using the
      selective culturing criteria of the AAP Committee on Child Abuse and Neglect:
      culturing when epidemiologically indicated (interpreted as the girl having
      another sexually transmitted disease [STD], a child sibling, child household
      member, a close child associate or a perpetrator with a known STD) or when the
      history and/or physical findings suggest the possibility of oral, genital, or
      rectal contact, or Siegel et al's more selective criteria: only culturing
      prepubertal girls for N gonorrhoeae if there is a vaginal discharge at the time
      of presentation or if there is a high risk for STD acquisition, defined as having
      a STD diagnosed, a sibling with a STD, contact with a perpetrator known to have a
      STD, contact with multiple perpetrators, or Tanner stage III or above.
      CONCLUSION: Both the selective criteria of the AAP Committee on Child Abuse and
      Neglect and the more selective criteria of Siegel et al as we interpreted them
      were accurate when applied to identifying girls with vaginal gonococcal
      infections in our study population.

PMID- 9164805
TI  - A randomized controlled trial of group versus individual well child care for high
      risk children: maternal-child interaction and developmental outcomes.
AB  - OBJECTIVE: To determine if group well child care (GWCC) for high-risk children
      affects maternal-child interaction and development as compared to these outcomes
      in children receiving traditional individual well child care (IWCC). STUDY
      DESIGN: Randomized controlled trial. PARTICIPANTS: Infants less than 4 months old
      at the initiation of the study who came from high-risk families. Families were
      classified as high risk, and eligible for study participation, if the mother had
      one or more of the following characteristics: poverty, single marital status,
      less than a high school education, age less than 20 years at delivery, previous
      substance abuse, or a history of abuse as a child. SETTING: Two urban, university
      pediatric clinics in Seattle, Washington. INTERVENTIONS: Study children were
      randomized to receive GWCC or IWCC prior to the first study visit at the age of 4
      months. Study health supervision visits were scheduled at 4, 5, 6, 8, 10, 12, and
      15 months of age. For children randomized to receive GWCC, study visits consisted
      of an age-matched group discussion of child rearing issues, either preceding or
      following a brief physical examination. After the 15-month visit, development of
      study patients was assessed by the use of Bayley Scales of Infant Development
      (Bayley). Maternal-child interaction and the home environment were evaluated by
      the use of the Nursing Child Assessment Teaching Scale (NCATS) and the Home
      Observation for Measurement of the Environment (HOME), respectively. RESULTS: At
      least one outcome measure was obtained on 114 children; 86 patients completed all
      three outcome measures. Bayley psychomotor mean scores were 103.6 +/- 11.5 for
      GWCC patients versus 100.0 +/- 12.4 for those receiving IWCC (P = .14); mean
      scores for the mental section were 99.3 +/- 14.8 and 100.4 +/- 14.3, respectively
      (P = .71). The prevalence of high-risk maternal-child interactions was 10% in
      both the GWCC and IWCC groups. A high-risk home environment was found in 16% of
      IWCC patients versus 4% of those randomized to GWCC (odds ratio comparing IWCC to
      GWCC 4.6, 95% confidence interval 0.78, 26.0, after controlling for confounding
      variables). Provider time was similar among groups (mean number of
      minutes/patient/study visit: 19.8 +/- 5.6 and 20.4 +/- 6.7 for GWCC and IWCC,
      respectively, P = .66). CONCLUSION: GWCC is a viable alternative to IWCC for high
      risk children. Developmental outcomes and maternal-child interaction are at least
      as good for children who received GWCC as compared to traditional IWCC, without
      any increase in provider time required.

PMID- 9164806
TI  - A standard protocol for blood pressure measurement in the newborn.
AB  - OBJECTIVES: Improvements in neonatal care have resulted in increasing survival of
      extremely premature infants whose hospital course often runs into weeks or
      months. Some interventions during the acute care of these neonates, such as
      umbilical catheterization and use of steroids, not infrequently result in
      elevation of blood pressure (BP). It is, therefore, essential that these infants
      be monitored accurately for possible hypertension during their convalescence.
      Unfortunately, normative data on BP in this population are scant and comparison
      of data from various studies is hampered by methodologic differences in design.
      Studies in adults address the necessity for a restful state, adopting a
      comfortable position, and attempts to reduce the startle response to initial cuff
      inflation. Studies in the newborn using the oscillometric technique have not
      addressed these concerns. A standard BP measurement protocol was studied to
      determine the effect of ensuring a restful state, startle response to cuff
      inflation, and infant position on BP in clinically stable low birth weight
      infants after the first week of life. STUDY DESIGN: The Dianamap oscillometer was
      used to measure BP in infants with a birth weight <2500 g between 7 and 42 days
      postnatal age. Each infant was studied only once when they were clinically
      stable. BP was measured in two positions, prone and supine, in random order.
      Infants were studied at least 11/2 hours after their last feeding or medical
      intervention. An appropriate sized cuff was applied to the right upper arm and
      the infant was positioned according to randomization. The infant was then left
      undisturbed for at least 15 minutes or until the infant was sleeping or in a
      quiet awake state. Three successive BP recordings were taken at 2-minute
      intervals. The infant's position was then reversed and another 15 minutes of
      quiet time was allowed. Thereafter, a second set of three successive BP
      recordings were obtained. The most recent routine nursing BP measurement was also
      recorded. Data were analyzed using analysis of variance and are presented as
      means and standard errors of the mean. RESULTS: Sixty-four infants were studied.
      Birth weights ranged from 901 to 2423 g and gestational ages from 26 to 37 weeks.
      Overall, mean BP was significantly lower in the prone than supine positions (45.7
      +/- 0.7 vs 47.8 +/- 0.8 mm Hg, P < .002). In either position, the first
      measurement was significantly higher than the third (average difference was 3 mm
      Hg, P < .003). In general, the relationships among position and order of
      measurement were similar for systolic and diastolic BP. Mean BPs obtained by
      routine nurse measurements were significantly higher than those in either
      position using our standard protocol (54.4 vs 47.0 or 49.1 mm Hg, P < .003).
      Moreover, the routine nurse measurements varied more widely than did those
      obtained using the standard protocol. The standard deviation for the routine mean
      BP measurements by nurses was 11.4 compared with 6.8 and 8.2 for the first
      measurements in the prone and supine positions, respectively, with the standard
      protocol. The mean BP measurements made in the supine position (the highest
      measurements obtained) using the standard protocol were also significantly lower
      than published values: 57 of 64 measurements were less than the average mean BP
      for age described by Tan (J Pediatr. 1988; 112:266-270). CONCLUSION: The
      statistically significant difference between the prone and supine position and
      among successive measurements in each position are not clinically relevant. The
      clinically significant differences between measurements obtained with this
      standard protocol and routine nursing measurements or published data are the
      result of ensuring a restful state after cuff application. We believe that
      measurements thus obtained are more representative of true resting BPs in these
      infants. (ABSTRACT TRUNCATED)

PMID- 9164807
TI  - Lipoprotein (a): its role in childhood thromboembolism.
AB  - PURPOSE: Elevated lipoprotein (a) [LP (a)] concentrations are independent risk
      factors of coronary heart disease or stroke in young adults. To clarify its role
      in childhood thromboembolism, Lp (a) was measured in 72 children with
      thromboembolism. METHODS: In addition to Lp (a), defects of the protein C
      anticoagulant system, antithrombin, and antiphospholipid antibodies were
      investigated in children with arterial (n = 36) or venous (n = 36) thrombosis.
      RESULTS: Enhanced Lp (a) >50 mg/dL was diagnosed in 8 out of 36 children with
      arterial and 5 out of 36 patients with venous thrombosis. Of the 72 children, 25
      showed the factor V Leiden mutation, 10 showed protein C deficiency, 2 showed
      antithrombin deficiency, and 4 showed primary antiphospholipid syndrome. Three
      children with increased Lp (a) were heterozygous for the factor V Leiden
      mutation, and 1 girl showed additional protein C deficiency. CONCLUSIONS: Data of
      this study indicate that increased concentrations of Lp (a) play an important
      role in childhood thrombosis.

PMID- 9164808
TI  - Randomized trial of varying mineral intake on total body bone mineral accretion
      during the first year of life.
AB  - OBJECTIVE: The effect of varying mineral intakes on total body bone mass
      accretion during the first year of life in healthy full-term infants is unknown.
      The purpose of this study was to determine whether total body bone mass accretion
      during the first year of life was influenced by the calcium and phosphorus intake
      of an infant and whether early differences in bone accretion persist through 1
      year of age. DESIGN: This prospective, randomized trial was conducted in two
      phases. In phase I, 67 infants were randomized within the first 2 weeks of life
      into either a low (439 mg of calcium per liter and 240 mg of phosphorus per
      liter) or moderate (510 mg of calcium per liter and 390 mg of phosphorus per
      liter) mineral-containing formula feeding group. An additional group of 34 human
      milk-fed (low mineral) infants also was enrolled. Phase II involved an additional
      randomization of all infants at 6 months of age into moderate-mineral formula
      (see above), high-mineral formula (1350 mg of calcium per liter and 900 mg of
      phosphorus per liter), or cow milk (1230 mg of calcium per liter and 960 mg of
      phosphorus per liter) feeding group. Anthropometric measurements, nutrient
      intake, and total body bone mineral content (BMC) by dual-energy x-ray
      absorptiometry were measured at 1, 3, 6, 9, and 12 months. RESULTS: During the
      first 6 months, the moderate-mineral group had a greater increase in weight (3.42
      +/- 0.62 kg) compared with the human milk group (2.93 +/- 0.56 kg); the low
      mineral group (3.19 +/- 0.62 kg) was intermediate. Bone mass accretion differed
      in a similar direction, with the moderate-mineral feeding group having a greater
      increase than the human milk group and the low-mineral group being intermediate
      of the two. Including weight, length, and bone area as covariates, both the low
      mineral formula- and human milk-fed groups had similar BMC, which was lower than
      that of the moderate-mineral group at 3 and 6 months of age. Adjusted mean BMC
      values for the moderate-mineral formula-fed group compared with the low-mineral
      formula- and human milk-fed groups were 127.8 +/- 1.5 (SEM) g vs 119. 2 +/- 1.5
      and 122.1 +/- 1.4 g, respectively, at 3 months of age and 168.7 +/- 2.5 g vs
      157.6 +/- 2.5 and 158.7 +/- 2.4 g, respectively, at 6 months of age. The BMC at 6
      months of age among the formula-fed infants was correlated with both average
      dietary phosphorus intake (r = .592) and average daily calcium intake (r = .620)
      during the first 6 months. The relationships between BMC and these minerals
      remained significant even after controlling for caloric intake. It was not
      possible to determine the independent effects of dietary calcium and phosphorus
      on BMC because of the strong correlation of these minerals with each other.
      Despite significant differences in both calcium and phosphorus intakes during the
      second 6 months of life, there were no differences in growth parameters or bone
      mass accretion. Means for BMC, adjusted for body weight, length, and bone area,
      were not significantly different among feeding groups at either 9 or 12 months of
      age. Adjusted means were 199 +/- 2 (SEM) and 237 +/- 3 g at 9 and 12 months of
      age for infants receiving moderate-mineral formula; 198 +/- 2 and 236 +/- 3 g at
      9 and 12 months of age for infants receiving the high-mineral formulas and 202 +/
      5 and 233 +/- 5 g at 9 and 12 months of age for infants receiving cow milk. The
      gain in bone mass during the second 6 months differed by the first 6-month
      feeding group; mean changes in BMC between 6 and 12 months, adjusted for changes
      in weight, length, and bone area, were greater in human milk-fed infants than in
      either the low- or moderate-mineral-containing formula groups: 81 +/- 16 g in
      human milk-fed infants and 73 +/- 15 and 71 +/- 15 g in the low- and moderate
      mineral formula groups, respectively. Infants fed whole cow milk during the
      second 6 months were excluded from this analysis because of the small number of
      infants completing the study. By 12 months of age t

PMID- 9164809
TI  - Comparison of conventional anterior surgery and laparoscopic surgery for inguinal
      hernia repair.
AB  - BACKGROUND: Inguinal hernias can be repaired by laparoscopic techniques, which
      have had better results than open surgery in several small studies. METHODS: We
      performed a randomized, multicenter trial in which 487 patients with inguinal
      hernias were treated by extraperitoneal laparoscopic repair and 507 patients were
      treated by conventional anterior repair. We recorded information about
      postoperative recovery and complications and examined the patients for
      recurrences one and six weeks, six months, and one and two years after surgery.
      RESULTS: Six patients in the open-surgery group but none in the laparoscopic
      surgery group had wound abscesses (P=0.03), and the patients in the laparoscopic
      surgery group had a more rapid recovery (median time to the resumption of normal
      daily activity, 6 vs. 10 days; time to the return to work, 14 vs. 21 days; and
      time to the resumption of athletic activities, 24 vs. 36 days; P<0.001 for all
      comparisons). With a median follow-up of 607 days, 31 patients (6 percent) in the
      open-surgery group had recurrences, as compared with 17 patients (3 percent) in
      the laparoscopic-surgery group (P=0.05). All but three of the recurrences in the
      latter group were within one year after surgery and were caused by surgeon
      related errors. In the open-surgery group, 15 patients had recurrences during the
      first year, and 16 during the second year. Follow-up was complete for 97 percent
      of the patients. CONCLUSIONS: Patients with inguinal hernias who undergo
      laparoscopic repair recover more rapidly and have fewer recurrences than those
      who undergo open surgical repair.

PMID- 9164810
TI  - An outbreak in 1996 of cyclosporiasis associated with imported raspberries. The
      Cyclospora Working Group.
AB  - BACKGROUND: Cyclospora cayetanensis is a parasite that causes gastroenteritis.
      Until last year most of the documented cases of cyclosporiasis in North America
      were in overseas travelers. In 1996, a large outbreak of cyclosporiasis occurred
      in North America. We investigated this outbreak. METHODS: Health departments
      solicited information from clinicians and laboratories on cases of
      cyclosporiasis, which were then reported to the Centers for Disease Control and
      Prevention and to Health Canada. We conducted retrospective cohort studies for
      the cases associated with events (e.g., luncheons) and attempted to identify the
      sources of the implicated food. RESULTS: A total of 1465 cases of cyclosporiasis
      were reported by 20 states, the District of Columbia, and 2 provinces. Of these
      cases, 978 (66.8 percent) were laboratory confirmed and 725 (49.5 percent) were
      associated with 55 events that were held from May 3 through June 14. Raspberries
      were definitely served at 50 events and may have been served at 4 events. For 27
      of the 41 events for which adequate data were available (65.8 percent), the
      associations between the consumption of berries (raspberries with or without
      other berries) and cyclosporiasis were statistically significant (P<0.05). For
      all 29 events for which there were good data, the raspberries definitely came
      from Guatemala (21 events, 72.4 percent) or may have come from Guatemala (8
      events, 27.6 percent). As few as five Guatemalan farms could have accounted for
      the 25 events for which the raspberries could be traced to a single exporter per
      event. The mode of contamination of the raspberries remains unclear. CONCLUSIONS:
      This large outbreak of cyclosporiasis in North America in 1996 was associated
      with the consumption of Guatemalan raspberries. The outbreak illustrates the need
      to consider that a local cluster of foodborne illness may be part of a widespread
      outbreak and to pursue investigations to the source of the implicated vehicle.

PMID- 9164811
TI  - Aluminum neurotoxicity in preterm infants receiving intravenous-feeding
      solutions.
AB  - BACKGROUND: Aluminum, a contaminant of commercial intravenous-feeding solutions,
      is potentially neurotoxic. We investigated the effect of perinatal exposure to
      intravenous aluminum on the neurologic development of infants born prematurely.
      METHODS: We randomly assigned 227 premature infants with gestational ages of less
      than 34 weeks and birth weights of less than 1850 g who required intravenous
      feeding before they could begin enteral feeding to receive either standard or
      specially constituted, aluminum-depleted intravenous-feeding solutions. The
      neurologic development of the 182 surviving infants who could be tested was
      assessed by using the Bayley Scales of Infant Development at 18 months of age.
      RESULTS: The 90 infants who received the standard feeding solutions had a mean
      (+/-SD) Bayley Mental Development Index of 95+/-22, as compared with 98+/-20 for
      the 92 infants who received the aluminum-depleted solutions (P=0.39). In a
      planned subgroup analysis of infants in whom the duration of intravenous feeding
      exceeded the median and who did not have neuromotor impairment, the mean values
      for the Bayley Mental Development Index for the 39 infants who received the
      standard solutions and the 41 infants who received the aluminum-depleted
      solutions were 92+/-20 and 102+/-17, respectively (P=0.02). The former were
      significantly more likely (39 percent, vs. 17 percent of the latter group;
      P=0.03) to have a Mental Development Index of less than 85, increasing their risk
      of subsequent educational problems. For all 157 infants without neuromotor
      impairment, increasing aluminum exposure was associated with a reduction in the
      Mental Development Index (P=0.03), with an adjusted loss of one point per day of
      intravenous feeding for infants receiving the standard solutions. CONCLUSIONS: In
      preterm infants, prolonged intravenous feeding with solutions containing aluminum
      is associated with impaired neurologic development.

PMID- 9164812
TI  - Molecular basis of the long-QT syndrome associated with deafness.

PMID- 9164813
TI  - Images in clinical medicine. Congenital long-QT syndrome.

PMID- 9164814
TI  - Cancer undefeated.
AB  - BACKGROUND: Despite decades of basic and clinical research and trials of
      promising new therapies, cancer remains a major cause of morbidity and mortality.
      We assessed overall progress against cancer in the United States from 1970
      through 1994 by analyzing changes in age-adjusted mortality rates. METHODS: We
      obtained from the National Center for Health Statistics data on all deaths from
      cancer and from cancer at specific sites, as well as on deaths due to cancer
      according to age, race, and sex, for the years 1970 through 1994. We computed age
      specific mortality rates and adjusted them to the age distribution of the U.S.
      population in 1990. RESULTS: Age-adjusted mortality due to cancer in 1994 (200.9
      per 100,000 population) was 6.0 percent higher than the rate in 1970 (189.6 per
      100,000). After decades of steady increases, the age-adjusted mortality due to
      all malignant neoplasms plateaued, then decreased by 1.0 percent from 1991 to
      1994. The decline in mortality due to cancer was greatest among black males and
      among persons under 55 years of age. Mortality among white males 55 or older has
      also declined recently. These trends reflect a combination of changes in death
      rates from specific types of cancer, with important declines due to reduced
      cigarette smoking and improved screening and a mixture of increases and decreases
      in the incidence of types of cancer not closely related to tobacco use.
      CONCLUSIONS: The war against cancer is far from over. Observed changes in
      mortality due to cancer primarily reflect changing incidence or early detection.
      The effect of new treatments for cancer on mortality has been largely
      disappointing. The most promising approach to the control of cancer is a national
      commitment to prevention, with a concomitant rebalancing of the focus and funding
      of research.

PMID- 9164815
TI  - Ion channels--basic science and clinical disease.

PMID- 9164816
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 17-1997. A 67-year-old woman with vomiting, bloody diarrhea, and
      azotemia.

PMID- 9164817
TI  - Old and new ways to repair inguinal hernias.

PMID- 9164818
TI  - Cyclosporiasis and raspberries--lessons for the future.

PMID- 9164819
TI  - Ion channels--molecular divining rods hit their clinical mark.

PMID- 9164820
TI  - The National Health Service Corps and inner-city hospitals.

PMID- 9164821
TI  - Effect of vitamin D receptor genotypes on calcium absorption, duodenal vitamin D
      receptor concentration, and serum 1,25 dihydroxyvitamin D levels in normal women.
AB  - It is well established that bone mineral density is under strong genetic control.
      Recently it was reported that the Bsm I restriction fragment length polymorphism
      of the vitamin D receptor (VDR) gene could account for up to 75% of the genetic
      variance in bone mineral density. However, the physiological basis for such an
      effect has not been established. The VDR gene codes for the vitamin D receptor
      protein which regulates intestinal calcium absorption. In order to assess the
      biochemical basis we studied the effect of common allelic variation of the VDR
      gene on intestinal VDR protein concentration, calcium absorption, and serum 1,25
      dihydroxyvitamin D (1,25(OH)2D). Ninety-two Caucasian women were genotyped for
      Bsm I and Taq I polymorphism at the VDR gene locus. From these we compared 49
      young women aged 25-35 years and 43 elderly women aged 65-83 years, who had all
      three measurements performed. There were no significant differences in intestinal
      VDR protein concentration, serum 1, 25(OH)2D, or radioactive calcium absorption
      among VDR genotype groups. Therefore, the small intestine does not seem to be a
      target for VDR gene polymorphism.

PMID- 9164822
TI  - Effect of tobacco consumption on bone mineral density in healthy young males.
AB  - Smoking is related to a decreased bone mass and increased risk of osteoporotic
      fractures. Nevertheless, the effect of smoking in males is poorly understood. The
      purpose of this study was to assess the repercussion of smoking on bone mass in
      otherwise healthy male smokers and its relationship with markers of mineral
      metabolism and hormone profile. We measured bone mineral density (BMD) in 57
      healthy males (26 nonsmokers, 31 smokers; aged 20-45 years) by dual X-ray
      absorptiometry (DXA, Hologic QDR1000) in the lumbar spine and proximal femur. In
      a subset we measured biochemical markers of bone metabolism and hormonal profile.
      We found significant differences in BMD between heavy smokers (more than 20
      cigarettes/day) and nonsmokers in all skeletal sites. Serum levels of
      dehydroepiandrosterone sulfate (S-DHEAS) were lower in smokers and correlated
      with femoral BMD measurements. No significant differences in bone turnover
      markers were found. Our findings show that smoking by healthy young males is
      associated with decreased bone mass.

PMID- 9164823
TI  - Alteration in the extent of collagen I hydroxylation, isolated from femoral heads
      of women with a femoral neck fracture caused by osteoporosis.
AB  - The aim of this study was to investigate the extent of lysyl and prolyl
      hydroxylation of collagen I in osteoporosis and compare it with collagen I from
      "bone healthy" individuals. Collagen I was isolated from femoral heads of
      osteoporotic women, from women suffering from osteoarthrosis of the hip, and from
      healthy women 60-85 years of age. The femoral heads were dissected into compact
      and trabecular bone of the neck region and from trabecular bone of the head
      region, and collagen I was extracted by limited pepsin digestion. The amino acid
      analysis of individual alpha-chains showed a remarkably higher degree of
      hydroxylation of lysine residues both in the alpha1(I)- and in the alpha2(I)
      chains in osteoporotic bone compared with osteoarthrotic and "normal" bone,
      whereas the prolyl hydroxylation was nearly unchanged. The lysyl
      overhydroxylation was observed in the compact as well as in the trabecular bone
      of osteoporotic femoral heads. These biochemical alterations may play a crucial
      role in the pathogenesis of osteoporosis.

PMID- 9164824
TI  - Overnight suppression of parathyroid hormone and bone resorption markers by
      active absorbable algae calcium. A double-blind crossover study.
AB  - In order to study the effect of Ca supplementation on the nocturnal rise of PTH
      and bone resorption, a double-blind, placebo-controlled study was carried out on
      9 healthy male volunteers. Regimen A consisted of an oral dose of 150 mg Ca as
      AAACa after each meal and 450 mg at bedtime; B consisted of 300 mg after each
      meal and C was placebo. Plasma ionized Ca was significantly higher in A than in B
      at 6 a.m. the next morning and urinary Ca/Cr after 5 days was higher in A than in
      B and C. Plasma intact PTH fell by 19 +/- 4 pg/ml in A, 8 +/- 7 in B, and 1 +/- 7
      after 1 day, and significantly decreased by 29 +/- 8 in A, increased by 11 +/- 11
      in B, and 5 +/- 7 in C after 5 days (A and B, and A and C, p = 0.0242 and 0.0433,
      respectively), with increases of % tubular reabsorption of phosphorus. Urinary
      excretion of cross-linked collagen degradation product (Crosslaps) was 40 +/- 10%
      of the baseline in A, 97 +/- 22 in B, and 173 +/- 30 in C (A and C, P = 0.0061)
      after 5 days. Systolic blood pressure at 6 a.m. fell by 17 +/- 4 mmHg A, 24 +/- 3
      in B, and 4 +/- 2 in C. Highly biologically available AAACa effectively
      suppressed nocturnal rise of PTH and bone resorption markers in 5 days.

PMID- 9164825
TI  - Regulation of c-fos and c-jun expression by calcitonin in human breast cancer
      cells.
AB  - Breast cancer cells (BCC) have calcitonin (CT) receptors, yet the action of the
      hormone on these cells is largely unknown. We found that CT produced a strong and
      transient time- and dose-dependent increase in c-fos mRNA in BCC lines. This
      event was prevented by a protein kinase A (PKA) inhibitor, H89. CT alone did not
      influence the expression of c-jun and of the tissue inhibitors of
      metalloproteases (timp) -1 and -2 mRNAs; however, it reduced the induction of
      these mRNAs by the protein kinase C (PKC) activator phorbol 12-myristate 13
      acetate (PMA), without apparent changes in the half-life of the mRNA (measured
      for c-jun). Along the same line, CT reduced the c-jun induction and T-47D growth
      stimulation by epidermal growth factor (EGF) and insulin. These effects were
      mimicked by forskolin and/or prevented by H89, suggesting that PKA activation was
      involved. These results indicate that CT modulates in BCC the mRNA levels of two
      important growth-related early response genes (c-fos and c-jun) and of two other
      genes (timp-1 and -2) involved in the control of metastatic events.

PMID- 9164826
TI  - Estrogen, progesterone and testosterone receptors in human fetal cartilaginous
      tissue: immunohistochemical studies.
AB  - Computerized image analysis was used to study the distribution in cartilage of
      receptors to estrogen, progesterone, and testosterone during human fetal
      development. We have examined three histologically distinct cell groups
      (hypertrophic, proliferating, and reserve zones) in long bones, vertebrae, and
      trachea from 19 fetuses. Comparisons were made across gender and gestational age.
      Contrasting with controls, we examined the density of receptors, the size of the
      nuclear area in which the receptors were detected, the number of hormone receptor
      bearing cells, and the total receptor quantity per sample. We found that
      estrogen, progesterone, and testosterone receptors were detected in the nuclei of
      all cell types, in both female and male embryonic cartilaginous tissue. Gender
      differences were small and inconsistent. Changes associated with gestational age
      depicted a pattern of hormone receptor manifestation, shifting from the immature
      cell types to more differentiated cells. This was evident from the receptor
      densities and from the cellular area in which receptors were sighted. These
      dynamics are accompanied by a general increase in receptor content per sample,
      brought about by the concomitant increase in receptor containing area size and
      cell number. The increase in receptor levels seems to reflect the maturation and
      growth of the fetal skeleton.

PMID- 9164827
TI  - Zinc enhancement of 17beta-estradiol's anabolic effect in osteoblastic MC3T3-E1
      cells.
AB  - The anabolic effect of 17beta-estradiol in osteoblastic MC3T3-E1 cells was
      investigated. The cells were cultured for 3 days in the medium containing either
      vehicle or 17beta-estradiol (10(-11)-10(-9) M). 17beta-Estradiol significantly
      increased alkaline phosphatase activity and protein concentration in the cells.
      The steroid (10(-9) M) also significantly elevated the cell numbers and the
      cellular DNA content. The anabolic effect by 17beta-estradiol was blocked by the
      presence of dipicolinate (10(-3) M), a chelator of zinc ion, suggesting a role of
      cellular zinc in osteoblastic cell function. The presence of zinc sulfate (10(-5)
      M) or beta-alanyl-L-histidinato zinc (AHZ) (10(-5) M) significantly enhanced the
      17beta-estradiol (10(-10) or 10(-9) M)-induced increase of alkaline phosphatase
      activity and protein concentration in the cells; the effect of AHZ was greater
      than that of zinc sulfate. The enhancement by zinc compounds was not based on the
      augmentation of osteoblastic cell numbers. The co-addition of cycloheximide (10(
      6) M), an inhibitor of protein synthesis, completely blocked the zinc compound
      (10(-5) M)-induced enhancement of 17beta-estradiol's (10(-9) M) effect to
      increase alkaline phosphatase activity and protein concentration in the cells.
      Moreover, the anabolic effect of 17beta-estradiol together with or without zinc
      compounds was abolished by the presence of staurosporine (10(-8) M), an inhibitor
      of protein kinase C, or of okadaic acid (10(-7) M), an inhibitor of protein
      phosphatase. The present study demonstrates that the anabolic effect of 17beta
      estradiol is enhanced by zinc-chelating dipeptide in osteoblastic MC3T3-E1 cells,
      and that the enhancing effect may involve protein synthesis and protein kinase
      activity.

PMID- 9164828
TI  - Influence of electromagnetic fields on bone mass and growth in developing rats: a
      morphometric, densitometric, and histomorphometric study.
AB  - The effect of electromagnetic fields on bone is debated. In an experimental study
      of this effect, we compared two lots of growing female rates (both lots n = 15,
      age 3 weeks, average weight 23.2 +/- 3.3 g), one of which was exposed to a 3-mT,
      100-Hz, Helmholtz-type electromagnetic field for 24 hours a day for 30 days, and
      the other of which served as the control. Bone development and bone mass were
      evaluated by morphometry, densitometry, and histomorphometry. The rats were
      killed at 30 days and weighed. The right femurs were dissected, measured, and
      weighed; bone densitometry was used to determine femoral bone mineral content
      (BMC) and density (BMD), and histomorphometry of the nondecalcified bone was used
      to determine trabecular bone volume (Cn-BV-TV%), number (Tb-N mm) and thickness
      (Tb-Th microm), intertrabecular space (Tb-Sp microm) and growth cartilage
      thickness (Gc-Th microm). In the rats exposed to the electromagnetic field, BMC
      and BMD (P = 0.019 and P = 0.002, respectively) and Cn-BV-TV, Tb-N, Tb-Th (P =
      0.005, P = 0.036, and P = 0.027, respectively) all were decreased, whereas Tb-Sp
      was increased (P = 0.002). There were no significant differences in initial and
      final body weight, or in final femur weight, femur length, and GC-Th. These
      findings indicate that electromagnetic fields of the type used here reduced bone
      formation and increased bone resorption without affecting bone development in
      rats.

PMID- 9164829
TI  - The effects of magnesium on hydroxyapatite formation in vitro from CaHPO4 and
      Ca4(PO4)2O at 37.4 degrees C.
AB  - The effects of magnesium ion on the formation of calcium-deficient hydroxyapatite
      [Ca9HPO4(PO4)5OH, CDHAp] from CaHPO4 and Ca4(PO4)2O dissolution were investigated
      using two magnesium sources: Mg3(PO4)2 (chemical system 1) or MgCl2 . H2O
      (chemical system 2) solutions. Because chloroapatite does not form from aqueous
      solutions, the use of two magnesium sources facilitated the determination of
      magnesium's role during synthetic hydroxyapatite formation in vitro and possible
      related effects during biomineralization. Isothermal calorimetry determined the
      progress of reactions. Two peaks are observed as heat is evolved during the
      formation of CDHAp in water at 37.4 degrees C. The nucleation and growth of CDHAp
      are the corresponding mechanisms. Although the time for complete reaction and
      total heat-of-reaction DeltaHr remain constant, the height of the first peak is
      reduced as the concentration of magnesium ion approaches 4 mM in either chemical
      system. Magnesium does not substitute into CDHAp even though there are calcium
      vacancies available. Subsequent increases cause the remaining heat peak to
      broaden and the time required for complete reaction to approach 24 hours as the
      initial MgCl2 concentration reaches 100 mM. Supersaturation limits chemical
      system 1 to Mg3(PO4)2 concentrations below 10 mM. A MgCl2 concentration of 3.16 M
      precludes CDHAp from forming for over 3 months; rather newberyite, MgHPO4 . 3H2O,
      precipitates. The morphology and surface area of the CDHAp formed in 100 mM MgCl2
      solution are comparable to those of CDHAp formed in water. The surface areas are
      approximately 80 m2/g. Magnesium concentrations below 4 mM only inhibit
      nucleation whereas those above 4 mM inhibit growth as well. Magnesium phosphate
      complexes are more inhibitory than magnesium chloride complexes. Increasing the
      liquid-to-solids ratio or agitation significantly increases the induction period
      before reaction initiates. Increasing the liquid-to-solids ratio increases the
      time span for growth whereas increasing agitation decreases the time span for
      growth. The large inhibitory effect of agitation suggests quiescent systems are
      more suitable for determining the kinetics of HAp formation. A magnesium
      inorganic chemical activity (alphaMg = gammaMg[Mg2+]) many times greater than
      that in biological fluids is required before inhibition of hydroxyapatite
      formation is realized.

PMID- 9164830
TI  - Ultrastructural immunolocalization of cartilage oligomeric matrix protein (COMP)
      in porcine growth cartilage.
AB  - Cartilage oligomeric matrix protein (COMP) is a macromolecule of yet unknown
      function with restricted distribution among tissues. In the present study, the
      ultrastructural localization of COMP in porcine immature joint cartilage and
      growth plate cartilage was semiquantitatively delineated. Tissues were fixed in a
      mixture of low concentration glutar- and paraformaldehyde, embedded at low
      temperature, and subjected to immunocytochemistry using polyclonal antibodies
      raised against bovine COMP. Protein A-coated colloidal gold was used for
      detection. The most intense immunolabeling for COMP was noted in the
      proliferative zones of the growth cartilages. Here the concentration of
      immunomarker was higher in the territorial compartment than in the pericellular
      and interterritorial areas. A low concentration of COMP was observed in the
      resting and hypertrophic zones. The immunolabeling for COMP did not differ
      between the three matrix compartments of these zones. Supported by previous data
      obtained by in situ hybridization, the concentration of immunolabeling in the
      proliferative zone indicates a high rate of COMP synthesis in proliferative
      chondrocytes. Hence, COMP may be considered as a marker for normal
      differentiation into proliferative chondrocytes.

PMID- 9164831
TI  - Increased turnover of small proteoglycans synthesized by human osteoblasts during
      cultivation with ascorbate and beta-glycerophosphate.
AB  - The small proteoglycan decorin had been localized previously at the d-band in the
      gap zone of collagen fibrils in nonmineralizing tissues. In bone matrix this zone
      is proteoglycan free and is at least in some species the place where
      mineralization along collagen fibrils starts. To study the metabolism of the
      small proteoglycans decorin and biglycan under mineralizing conditions,
      osteoblasts from human nasal bone were cultured for several weeks in the presence
      or absence of beta-glycerophosphate and ascorbate. An immediate consequence of
      the treatment was a reduced expression of decorin, as judged by immune
      precipitation, whereas the biosynthesis of biglycan was not affected. Pulse-chase
      experiments were performed with osteoblasts embedded in floating type I collagen
      gels. In the presence of beta-glycerophosphate and ascorbate, a more rapid
      turnover of both proteoglycans was noted; the one of biglycan reached statistical
      significance. Indirect evidence for an enhanced rate of proteoglycan endocytosis
      was obtained. This effect was not seen in cultured skin fibroblasts. Thus,
      osteoblasts respond rapidly to mineralizing conditions with alterations of small
      proteoglycan biosynthesis and turnover.

PMID- 9164832
TI  - Cartilage calcification and limb bud growth in the developing tich mouse embryo.
AB  - The tich mutation leads to the abnormal development of bones in mice such that a
      'V-shaped' tongue of noncalcified cartilage appears in the central portion of the
      proximal tibial growth plate. In this study, alcian green staining of cartilage
      glycosaminoglycans was used to demonstrate the pattern of limb development in
      embryos of stage-matched tich and normal, co-isogenic, A.TL mice from the
      earliest stages in skeletogenesis. The growth plates of normal A.TL siblings were
      symmetrical across the limb rudiment whereas the growth plate in tich siblings
      show the beginnings of a V-shaped tongue of cartilage reaching towards the
      diaphysis. This showed first at E16.5. It was apparent that the crown rump
      distance, tibia, ulna, and the length of calcified cartilage in tich were
      significantly shorter than A.TL. These results confirmed that calcification was
      not the primary defect in tich but point to a temporal dysfunction in growth
      factor expression (possibly bone morphogenetic proteins) that stems from early
      limb bud formation and translates through later stages in development.

PMID- 9164833
TI  - Complementary medical treatment for Colles' fracture: a comparative, randomized,
      longitudinal study.
AB  - In 45 women with Colles' fracture, two types of complementary medical treatment
      (calcitonin with calcium [SCT+Ca] and calcium alone [Ca]) were compared with
      placebo. Consecutive patients were assigned randomly to one of the three study
      groups at the time of inclusion in the study: 15 women (68.6 +/- 5.7 years) were
      given 100 IU/day I.M. of SCT plus 1200 mg of elemental Ca for 10 successive days
      each month; 15 women (71.7 +/- 6.1 years) were given only 1200 mg of elemental Ca
      for 10 days each month; and 15 women (66.9 +/- 7. 9 years) were treated with
      placebo. Biochemical and radiogrammetric studies were made at baseline and after
      1 year of treatment. In the SCT+Ca group tartrate-resistant acid phosphatase
      decreased (Wilcoxon test, P = 0.014) and the metacarpal index and the cortical
      and total area (CA/TA) ratio increased (both P = 0.001). In the group treated
      with Ca alone, no changes were observed. In the placebo group, the metacarpal
      index and CA/TA decreased (P = 0.015 and P = 0.007, respectively). Ca alone, at
      the dosage used here, inhibited bone loss after Colles' fracture. The addition of
      SCT to Ca administration not only impeded bone loss but significantly increased
      cortical bone mass.

PMID- 9164835
TI  - Deletion of 24 amino acids from the C-terminus of phosphatidylinositol transfer
      protein causes loss of phospholipase C-mediated inositol lipid signalling.
AB  - Phosphatidylinositol transfer protein alpha (PITPalpha) is a 32 kDa protein of
      270 amino acids that is essential for phospholipase C-mediated
      phosphatidylinositol bisphosphate hydrolysis. In addition, it binds and transfers
      phosphatidylinositol and phosphatidylcholine between membrane compartments in
      vitro. Here we have used limited proteolysis of PITPalpha by subtilisin to
      identify the structural requirements for function. Digestion by subtilisin
      results in the generation of a number of slightly smaller peptide fragments, the
      major fragment being identified as a 29 kDa protein. The fragments were resolved
      by size-exclusion chromatography and were found to be totally inactive in both in
      vivo PLC reconstitution assays and in vitro phosphatidylinositol transfer assays.
      N-terminal sequencing and MS of the major 29 kDa fragment shows that cleavage
      occurs at the C-terminus of PITP at Met246, leading to a deletion of 24 amino
      acid residues. We conclude that the C-terminus plays an important role in
      mediating PLC signalling in vivo and lipid transfer in vitro, supporting the
      notion that lipid transfer may be a facet of PITP function in vivo.

PMID- 9164836
TI  - Glutathione transferases catalyse the detoxication of oxidized metabolites (o
      quinones) of catecholamines and may serve as an antioxidant system preventing
      degenerative cellular processes.
AB  - o-Quinones are physiological oxidation products of catecholamines that contribute
      to redox cycling, toxicity and apoptosis, i.e. the neurodegenerative processes
      underlying Parkinson's disease and schizophrenia. The present study shows that
      the cyclized o-quinones aminochrome, dopachrome, adrenochrome and
      noradrenochrome, derived from dopamine, dopa, adrenaline and noradrenaline
      respectively, are efficiently conjugated with glutathione in the presence of
      human glutathione transferase (GST) M2-2. The oxidation product of adrenaline,
      adrenochrome, is less active as a substrate for GST M2-2, and more efficiently
      conjugated by GST M1-1. Evidence for expression of GST M2-2 in substantia nigra
      of human brain was obtained by identification of the corresponding PCR product in
      a cDNA library. Glutathione conjugation of these quinones is a detoxication
      reaction that prevents redox cycling, thus indicating that GSTs have a
      cytoprotective role involving elimination of reactive chemical species
      originating from the oxidative metabolism of catecholamines. In particular, GST
      M2-2 has the capacity to provide protection relevant to the prevention of
      neurodegenerative diseases.

PMID- 9164837
TI  - Evidence against an early signalling role for ceramide in Fas-mediated apoptosis.
AB  - We have investigated whether the increases in ceramide levels that occur during
      apoptosis in SKW 6.4 cells induced by anti-Fas antibody depend on the activation
      of caspases. Using cells prelabelled to equilibrium with [14C]acetate, it was
      shown that the amount of ceramide approximately doubled after 24 h incubation
      with anti-Fas, but the time course of ceramide changes was slower than that of
      anti-Fas-induced cell death. Complete inhibition of the effects of anti-Fas on
      cell death and on ceramide production was observed when the caspase inhibitor N
      benzyloxycarbonyl-Val-Ala-Asp-(O-methyl)fluoromethane (zVAD.fmk) was added
      together with anti-Fas, but N-benzyloxycarbonyl-Phe-Ala-fluoromethane (a
      structurally similar cathepsin B inhibitor) had no effect. Treatment of cells
      with the Ca2+-ionophore A23187 also doubled ceramide levels, but in this case the
      effect was complete within 2 h, was not blocked by zVAD.fmk and was not
      associated with increases in nuclear fragmentation. These results suggest that
      ceramide is not an upstream messenger in Fas-mediated apoptosis and may instead
      be produced as a consequence of processes downstream of the activation of
      caspases and increases in cytosolic calcium concentration.

PMID- 9164838
TI  - alpha-Glucosidase and N-acetylglucosamine-6-sulphatase are the major mannose-6
      phosphate glycoproteins in human urine.
AB  - Most newly synthesized lysosomal enzymes contain a transient carbohydrate
      modification, mannose 6-phosphate (Man-6-P), which signals their vesicular
      transport from the Golgi to the lysosome via Man-6-P receptors (MPRs). We have
      examined Man-6-P glycoproteins in human urine by using a purified soluble
      fragment of the soluble cation-independent MPR (sCI-MPR) as a preparative and
      analytical affinity reagent. In a survey of urine samples from seven healthy
      subjects, the pattern of Man-6-P glycoproteins detected with iodinated sCI-MPR as
      a probe in a blotting assay was essentially identical in each, regardless of sex
      or age. Two bands of approx. 100 and 110 kDa were particularly prominent. Man-6-P
      glycoproteins in human urine were purified by affinity chromatography on
      immobilized sCI-MPR. Seven distinct bands revealed by SDS/PAGE and Coomassie Blue
      staining were subjected to N-terminal sequence analysis. The prominent 100 and
      110 kDa Man-6-P glycoproteins were identified as N-acetylglucosamine-6-sulphatase
      and alpha-glucosidase respectively. This identification was confirmed by
      molecular mass determinations on the two major bands after deglycosylation.
      Sequence analysis revealed arylsulphatase A and several previously unidentified
      proteins as minor species. Man-6-P glycoproteins were also purified on an
      analytical scale to determine the proportion of a number of lysosomal enzyme
      activities represented by the mannose-6-phosphorylated forms. The lysosomal
      enzymes in urine containing the highest proportion of mannose-6-phosphorylated
      form were beta-mannosidase (82%), hexosaminidase (27%) and alpha-glucosidase
      (24%). The profiles of Man-6-P glycoproteins detected by blotting in urine and
      plasma were not similar, suggesting that the urinary species are not derived from
      the bloodstream.

PMID- 9164834
TI  - Biochemistry and pathology of radical-mediated protein oxidation.
AB  - Radical-mediated damage to proteins may be initiated by electron leakage, metal
      ion-dependent reactions and autoxidation of lipids and sugars. The consequent
      protein oxidation is O2-dependent, and involves several propagating radicals,
      notably alkoxyl radicals. Its products include several categories of reactive
      species, and a range of stable products whose chemistry is currently being
      elucidated. Among the reactive products, protein hydroperoxides can generate
      further radical fluxes on reaction with transition-metal ions; protein-bound
      reductants (notably dopa) can reduce transition-metal ions and thereby facilitate
      their reaction with hydroperoxides; and aldehydes may participate in Schiff-base
      formation and other reactions. Cells can detoxify some of the reactive species,
      e.g. by reducing protein hydroperoxides to unreactive hydroxides. Oxidized
      proteins are often functionally inactive and their unfolding is associated with
      enhanced susceptibility to proteinases. Thus cells can generally remove oxidized
      proteins by proteolysis. However, certain oxidized proteins are poorly handled by
      cells, and together with possible alterations in the rate of production of
      oxidized proteins, this may contribute to the observed accumulation and damaging
      actions of oxidized proteins during aging and in pathologies such as diabetes,
      atherosclerosis and neurodegenerative diseases. Protein oxidation may also
      sometimes play controlling roles in cellular remodelling and cell growth.
      Proteins are also key targets in defensive cytolysis and in inflammatory self
      damage. The possibility of selective protection against protein oxidation
      (antioxidation) is raised.

PMID- 9164839
TI  - Structural characterization of the products of hydroxyl-radical damage to leucine
      and their detection on proteins.
AB  - We have previously reported the formation of valine hydroperoxides and aldehydes
      from hydroxyl-radical attack on free valine and protein molecules. We have also
      demonstrated that the major degradation products of valine hydroperoxides by
      several biochemical and cellular systems are the corresponding hydroxides, and
      therefore proposed that hydroxyvalines may serve as useful in vivo markers for
      studying protein oxidation. Here we have undertaken the structural elucidation of
      the oxidation products of leucine, another amino acid which is very susceptible
      to peroxidation. Hydroxyl-radical (HO.) attack on l-leucine in the presence of
      oxygen, followed by NaBH4 reduction, gave rise to five major oxidation products
      which have been isolated and identified. On the basis of chemical and
      spectroscopic evidence, the five products have been identified as (2S)-gamma
      hydroxyleucine, (2S,4S)-delta-hydroxyleucine, (2S,4R)-delta-hydroxyleucine,
      (2S,4R)-4-methylproline (trans-4-methyl-l-proline) and (2S,4S)-4-methylproline
      (cis-4-methyl-l-proline). The three hydroxyleucines have been confirmed to be the
      reduction products of the corresponding hydroperoxyleucines, while the two
      proline analogues are from reduction of their corresponding cyclic Schiff bases.
      By HPLC analysis using post-column o-phthaldialdehyde derivatization, we have
      detected hydroxyleucines in the hydrolysates of tripeptides and proteins which
      had been gamma-radiolysed and treated with NaBH4. Furthermore, we demonstrate the
      occurrence of the hydroxyleucines on proteins in physiological and pathological
      samples. Hydroxyleucines, like hydroxyvalines, may provide useful in vivo markers
      for studying protein oxidation. In the present study we also investigated the
      competition between leucine, valine and phenylalanine for HO., and proposed a
      possible radical-transfer process in such free-radical reactions.

PMID- 9164841
TI  - Involvement of the N-terminal region of the human mineralocorticoid receptor
      hormone-binding domain in agonist and antagonist binding as revealed by a new
      monoclonal antibody.
AB  - To gain a better understanding of the mechanism of binding to the human
      mineralocorticoid receptor (hMR), we developed a new monoclonal antibody (mAb)
      raised against the hormone-binding domain (HBD). For this purpose, mice were
      immunized with a fusion protein including the sequence Thr729-Lys984 of hMR.
      After ELISA screening, mAb 18C7 was selected for its specificity towards the HBD.
      This antibody recognized both the denatured and native MR forms, as well as the
      hetero-oligomeric MR form and the transformed MR state. By using several HBD
      subfragments, the mAb 18C7 epitope was located in the N-terminal region of the
      HBD from Thr729 to Leu765. We then studied the effect of the antibody on
      aldosterone and progesterone binding to the hMR. When 18C7 was incubated with
      liganded MR, it was able to partly displace (20%) the hormone from its binding
      site. When 18C7 was incubated with MR before aldosterone or progesterone, the
      antibody inhibited 75-80% of the binding. The effect of 18C7 on the binding was
      similar with both hormones. A sucrose gradient analysis indicated the
      simultaneous presence of two kinds of receptor complexes: the steroid-MR complex
      and the antibody-MR complex. After its associated proteins, especially the heat
      shock protein hsp90, had been cross-linked with the hMR by dimethylpimelimidate,
      18C7 was still able to react with the receptor. Our results indicated that the
      epitope recognized by 18C7 was directly implicated in hormone binding. The lack
      of steroid binding of HBD mutants with the Thr729-Leu765 sequence deleted
      [Jalaguier, Mesnier, Leger and Auzou (1996) J. Steroid Biochem. Mol. Biol. 57, 43
      50] supports this hypothesis. Because of the similar behaviours of aldosterone
      and progesterone, we conclude that the N-terminal Thr729-Leu765 region of the HBD
      is similarly involved in the binding of both hormones.

PMID- 9164840
TI  - Differential regulation of natriuretic peptide receptors on ciliary body
      epithelial cells.
AB  - Atrionatriuretic peptide (ANP) lowers intraocular pressure in the eyes of humans
      and rabbits. We examined the effects of natriuretic peptides on cGMP formation
      and 125I-labelled-ANP binding to cultured cells derived from ciliary body
      epithelium, the site of aqueous humour formation in the eye. ANP, brain
      natriuretic peptide (BNP) and C-natriuretic peptide (CNP) at 1 microM stimulated
      cGMP formation 8.2(+/-1.2)-fold, 4.8(+/-0.6)-fold and 87.3(+/-12.1)-fold
      respectively. 125I-ANP bound to intact cells at a single site, with a
      dissociation constant KD=0.30+/-0.01 nM. BNP was as effective as ANP in
      displacing 125I-ANP, whereas CNP displaced label with a slightly higher IC50.
      125I-ANP binding was displaced >95% by c-ANP, a specific ligand for natriuretic
      peptide C receptors (NPR-C). Cross-linking of 125I-ANP to cells labelled
      predominantly a protein of Mr 62000. These data suggest that 125I-ANP binding was
      primarily to NPR-C, whereas cGMP stimulation occurred primarily via natriuretic
      peptide B receptors (NPR-B). Vasopressin and histamine, both activators of the
      inositol phosphate/diacylglycerol phosphate pathway in non-pigmented ciliary
      epithelial cells, inhibited CNP stimulation of guanylate cyclase (NPR-B) and 125I
      ANP binding (NPR-C) by 30-38%. Inhibition was mimicked by PMA, dioctanoylglycerol
      and phorbol didecanoate, whereas 4alpha phorbol didecanoate had no effect.
      Staurosporine and bisindolylmaleimide both blocked inhibition of 125I-ANP binding
      and cGMP formation by PMA. These results suggest that protein kinase C (PKC) down
      regulates both NPR-B and NPR-C. PKC down-regulation of NPR-B varied inversely
      with CNP concentration. Inhibition by 1 microM PMA was 30.6(+/-4.0)% with 500 nM
      CNP, but 83.4(+/-8.8)% with 10 nM CNP, indicating that increasing CNP could
      partially overcome inhibition by PMA. Since extracellular CNP levels were not
      affected by PKC activation, the effect of PKC on NPR-B is best explained as a
      reduction in NPR-B affinity for CNP. NPR-C measured as 125I-ANP binding was
      likewise reduced 36.4(+/-5.1)% by exposure to PMA. In contrast with NPR-B
      inhibition, however, inhibition of NPR-C was due largely to a reduction in the
      number of receptor binding sites per cell rather than a reduction in receptor
      affinity for ligand. The data therefore suggest that both NPR-B and NPR-C are
      down-regulated by PKC, but that the mechanisms of down-regulation of the two
      receptors are different.

PMID- 9164842
TI  - Gene expression of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in a
      poorly ketogenic mammal: effect of starvation during the neonatal period of the
      piglet.
AB  - The low ketogenic capacity of pigs correlates with a low activity of
      mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase. To identify the
      molecular mechanism controlling such activity, we isolated the pig cDNA encoding
      this enzyme and analysed changes in mRNA levels and mitochondrial specific
      activity induced during development and starvation. Pig mitochondrial synthase
      showed a tissue-specific expression pattern. As with rat and human, the gene is
      expressed in liver and large intestine; however, the pig differs in that mRNA was
      not detected in testis, kidney or small intestine. During development, pig
      mitochondrial HMG-CoA synthase gene expression showed interesting differences
      from that in the rat: (1) there was a 2-3 week lag in the postnatal induction;
      (2) the mRNA levels remained relatively abundant through the suckling-weaning
      transition and at maturity, in contrast with the fall observed in rats at similar
      stages of development; and (3) the gene expression was highly induced by fasting
      during the suckling, whereas no such change in mitochondrial HMG-CoA synthase
      mRNA levels has been observed in rat. The enzyme activity of mitochondrial HMG
      CoA synthase increased 27-fold during starvation in piglets, but remained one
      order of magnitude lower than rats. These results indicate that post
      transcriptional mechanism(s) and/or intrinsic differences in the encoded enzyme
      are responsible for the low activity of pig HMG-CoA synthase observed throughout
      development or after fasting.

PMID- 9164843
TI  - Bcl-2 does not require Raf kinase activity for its death-protective function.
AB  - It has been widely accepted that the oncogene product bcl-2 protects mammalian
      cells from programmed cell death (apoptosis). The molecules and signalling
      pathways upon which bcl-2 acts are, however, still ill-defined. Recently, bcl-2
      was shown to interact with c-raf-1 in vitro. Furthermore, an active form of c-raf
      1 delayed apoptosis induced by trophic factor deprivation and enhanced the death
      suppressive function of bcl-2 when co-expressed. This has led to the hypothesis
      that bcl-2 communicates cell-death protection via a raf-dependent signal
      transduction pathway. Here we show, by various immunological and biochemical
      methods, that bcl-2 does not stably associate with c-raf-1 in cellular extracts
      prepared from fibroblasts before or after treatment with agents that induce
      apoptosis. Unexpectedly, bcl-2 function is entirely maintained, if not improved,
      when raf-dependent signalling is experimentally abrogated. In fact, bcl-2 allows
      the stable overexpression of a kinase-defective dominant-negative raf mutant that
      usually interferes with cell viability and/or proliferation. Our results indicate
      that bcl-2 does not require c-raf-1 kinase activity and an associated mitogen
      activated protein kinase signalling pathway for its survival function. This
      property may be exploited to dissect cellular events that are dependent or
      independent of c-raf-1 kinase activity.

PMID- 9164844
TI  - Characterization of Rab3A, Rab3B and Rab3C: different biochemical properties and
      intracellular localization in bovine chromaffin cells.
AB  - In this study we examined the biochemical properties and subcellular localization
      of Rab3A, Rab3B and Rab3C in bovine adrenal chromaffin cells. The Kd for
      guanosine 5'-[gamma-thio]triphosphate (GTP[S]) of the three Rab3 proteins was 15,
      2700 and 204 nM for Rab3A, Rab3B and Rab3C respectively. The intrinsic GTPase
      activity of the three Rab3 proteins seemed similar and was increased approx. 3
      fold by bovine chromaffin cell lysate. Truncation of the C-terminal 31 amino acid
      residues decreased the binding affinity for GTP[S] of the three Rab3 proteins.
      When the C-terminus of Rab3C was replaced with that of Rab3A, the binding
      affinity of Rab3C for GTP[S] was decreased, but the replacement did not affect
      the affinity of Rab3B for GTP[S]. Immunostaining experiments showed that Rab3A,
      Rab3B and Rab3C are localized separately within chromaffin cells. Anti-Rab3A and
      anti-Rab3C antibodies stained vesicle-like structures, whereas anti-Rab3B
      antibody distinctly stained the plasma membrane. In summary, bovine chromaffin
      cells express the three Rab3 proteins but the subcellular localization and
      biochemical properties of the three Rab3 proteins are distinct.

PMID- 9164845
TI  - Transcriptional and post-transcriptional mechanisms can regulate cell-specific
      expression of the human Pi-class glutathione S-transferase gene.
AB  - Previous studies from this laboratory have identified transcriptional mechanisms
      that are utilized to increase expression of the human glutathione S-transferase
      gene GSTP1 in a multidrug-resistant derivative (VCREMS) of the human mammary
      carcinoma cell line MCF7 [Moffat, McLaren and Wolf (1994) J. Biol. Chem. 269,
      16397-16402]. The data presented here provide strong evidence that post
      transcriptional mechanisms can also play an important role in determining cell
      specific expression of the GSTP1 gene. GSTP1 mRNA levels were shown to be
      elevated 3.1-fold in the human bladder carcinoma cell line EJ compared with
      VCREMS cells. Despite this observation, transient transfection assays revealed a
      decreased rate of GSTP1 promoter activity in EJ cells. Indeed, GSTP1
      transcriptional repressor activity, mediated by a region located between
      nucleotides -105 and -86 (as we have previously described in MCF7 cells), was
      observed in EJ cells. However, in contrast with our results in MCF7 cells, the EJ
      repressor activity did not displace the essential nuclear complex bound to the C1
      promoter element (-73 to -54) in vitro. In addition, competition experiments
      indicated that an AP-1-like protein is an integral component of the C1-bound
      complex in EJ cells. Interestingly, experiments utilizing actinomycin D to
      inhibit transcription demonstrated significantly greater stability of GSTP1 mRNA
      in EJ cells than in VCREMS cells. These findings suggest that cell-specific
      differences in the rates of GSTP1 mRNA decay provide the predominant mechanism
      responsible for elevated expression of the GSTP1 gene in EJ cells.

PMID- 9164846
TI  - Cloning and characterization of two glutathione S-transferases from a DDT
      resistant strain of Anopheles gambiae.
AB  - Two cDNA species, aggst1-5 and aggst1-6, comprising the entire coding region of
      two distinct glutathione S-transferases (GSTs) have been isolated from a 1,1,1
      trichloro-2,2-bis-(p-chlorophenyl)ethane (DDT) resistant strain (ZANDS) of
      Anopheles gambiae. The nucleotide sequences of these cDNA species share 80.2%
      identity and their derived amino acid sequences are 82.3% similar. They have been
      classified as insect class I GSTs on the basis of their high sequence similarity
      to class I GSTs from Drosophila melanogaster and Musca domestica and they are
      localized to a region of an An. gambiae chromosome known to contain further class
      I GSTs. The genes aggst1-5 and aggst1-6 were expressed at high levels in
      Escherichia coli and the recombinant GSTs were purified by affinity
      chromatography and characterized. Both agGST1-5 and agGST1-6 showed high activity
      with the substrates 1-chloro-2,4-dinitrobenzene and 1, 2-dichloro-4-nitrobenzene
      but negligible activity with the mammalian theta class substrates, 1,2-epoxy-3-(4
      nitrophenoxy)propane and p-nitrophenyl bromide. Despite their high level of
      sequence identity, agGST1-5 and agGST1-6 displayed different kinetic properties.
      Both enzymes were able to metabolize DDT and were localized to a subset of GSTs
      that, from earlier biochemical studies, are known to be involved in insecticide
      resistance in An. gambiae. This subset of enzymes is one of three in which the
      DDT metabolism levels are elevated in resistant insects.

PMID- 9164847
TI  - Regulatory elements in the first intron of the rat fatty acid synthase gene.
AB  - Sequence elements have been identified within the 1.2 kb-long first intron of the
      fatty acid synthase (FAS) gene that mediate both positive and negative effects on
      transcription. The negative regulatory element, when positioned downstream of
      either the FAS or simian virus 40 promoter, down-regulates the expression of a
      coupled reporter gene in an orientation-dependent manner. Sequences mediating
      this effect have been mapped, by deletion mutagenesis, to two regions
      approximately within nucleotides +405 to +768 and +924 to +1083. Both regions
      contain sequence elements that are strongly protected from DNase I digestion by
      nuclear extracts prepared from liver, but not by those prepared from spleen. The
      results of run-on assays performed with nuclei derived from tissues that express
      FAS at either high or low levels indicate that the different rates of
      transcription of the endogenous FAS gene result from differences in the extent of
      initiation, so it is unlikely that the negative effect is caused by
      transcriptional pausing in the first intron. The positive element maps to nt +292
      to +297 and corresponds to an authentic binding site for upstream stimulatory
      factor (USF). This USF-binding element can up-regulate transcription from a
      heterologous promoter in a position- and orientation-independent manner. However,
      in the context of the entire FAS first intron, the effect of the USF-binding site
      is masked unless the effect of the negative elements is ablated by mutagenesis.
      These results suggest that the dominant negative element of the first intron may
      play a role in determining the tissue-specific expression of the FAS gene.

PMID- 9164848
TI  - Metabolic evidence for PtdIns(4,5)P2-directed phospholipase C in permeabilized
      plant protoplasts.
AB  - Comparison of the sequences of the genes encoding phospholipase C (PLC) which
      have been cloned to date in plants with their mammalian counterparts suggests
      that plant PLC is similar to PLCdelta of mammalian cells. The physiological role
      and mechanism of activation of PLCdelta is unclear. It has recently been shown
      that Ins(1,4,5)P3 may not solely be the product of PtdIns(4,5)P2-directed PLC
      activity. Enzyme activities capable of producing Ins(1,4,5)P3 from endogenous
      inositol phosphates are present in Dictyostelium and also in rat liver.
      Significantly it has not been directly determined whether Ins(1,4,5)P3 present in
      higher plants is the product of a PtdIns(4, 5)P2-directed PLC activity. Therefore
      we have developed an experimental strategy for the identification of d
      Ins(1,4,5)P3 in higher plants. By the use of a short-term non-equilibrium
      labelling strategy in permeabilized plant protoplasts, coupled to the use of a
      'metabolic trap' to prevent degradation of [32P]Ins(1,4,5)P3, we were able to
      determine the distribution of 32P in individual phosphate esters of Ins(1,4,5)P3.
      The [32]Ins(1,4,5)P3 identified showed the same distribution of label in
      individual phosphate esters as that of [32P]PtdIns(4,5)P2 isolated from the same
      tissue. We thus provide in vivo evidence for the action of a PtdIns(4,5)P2
      directed PLC activity in plant cells which is responsible for the production of
      Ins(1,4,5)P3 observed here. This observation does not, however, exclude the
      possibility that in other cells or under different conditions Ins(1,4,5)P3 can be
      generated by alternative routes.

PMID- 9164849
TI  - Transcriptional activation of human 12-lipoxygenase gene promoter is mediated
      through Sp1 consensus sites in A431 cells.
AB  - The functional 5' flanking region of the human 12-lipoxygenase in epidermoid
      carcinoma A431 cells was characterized. By a primer extension method, the
      transcription initiation sites were mapped at -47 adenosine, -48 guanosine and 
      55 guanosine upstream of the ATG translation start codon. Transient transfection
      with a series of 5' and 3' deletion constructs showed that the 5' flanking region
      spanning from -224 to -100 bp was important for the basal expression of 12
      lipoxygenase gene. Gel mobility shift assays with antibodies of transcription
      factors showed that both Sp1 and Sp3 required highly GC-rich Sp1 sites within
      this region for binding. Disruption of two Sp1 recognition motifs residing at 
      158 to -150 bp and -123 to -114 bp by site-directed mutagenesis markedly reduced
      the basal 12-lipoxygenase promoter activity and abolished the retarded bands in a
      gel-shift assay, indicating that these two Sp1-binding sites were essential for
      gene expression. The same two Sp1-binding sites in this promoter region were also
      responsible for epidermal growth factor (EGF)-induced expression of 12
      lipoxygenase gene. Moreover, EGF also induced the transcriptional activation of
      luciferase driven by SV40 early promoter, which contained rich Sp1-binding sites.
      Taken together, the results suggest that two specific Sp1 consensus sites are
      involved in the mediation of the basal promoter activity as well as EGF induction
      of the 12-lipoxygenase gene and that Sp1 and Sp3 transcription factors might have
      a role in their regulation.

PMID- 9164850
TI  - Identification of integrin-stimulated sites of serine phosphorylation in FRNK,
      the separately expressed C-terminal domain of focal adhesion kinase: a potential
      role for protein kinase A.
AB  - Focal adhesion kinase (pp125(FAK)) is a protein tyrosine kinase that is localized
      to focal adhesions in many cell types and which undergoes tyrosine
      phosphorylation after integrin binding to extracellular matrix. In some cells the
      C-terminal non-catalytic domain of pp125(FAK) is expressed as a separate protein
      referred to as FRNK (FAK-related, non-kinase). We have previously shown that
      overexpression of FRNK inhibits tyrosine phosphorylation of pp125(FAK) and its
      substrates as well as inhibiting cell spreading on fibronectin. In this report we
      identify Ser148 and Ser151 as residues in FRNK that are phosphorylated after
      tyrosine phosphorylation of pp125(FAK) and in response to integrin binding to
      fibronectin. Tyrosine phosphorylation of pp125(FAK) appears to be an early event
      after integrin occupancy, and serine phosphorylation of FRNK occurs significantly
      later. Treatment of fibroblasts with a series of protein kinase A inhibitors
      delayed serine phosphorylation of FRNK as well as cell spreading on fibronectin
      and tyrosine phosphorylation of pp125(FAK). However, these PKA inhibitors are
      unlikely to delay cell spreading simply by preventing serine phosphorylation of
      FRNK, as overexpression of FRNK containing mutations of Ser148 and Ser151 either
      singly or jointly to either alanine or glutamate residues did not significantly
      alter the ability of FRNK to act as an inhibitor of pp125(FAK).

PMID- 9164851
TI  - Identification of membrane dipeptidase as a major glycosyl-phosphatidylinositol
      anchored protein of the pancreatic zymogen granule membrane, and evidence for its
      release by phospholipase A.
AB  - Membrane dipeptidase (EC 3.4.13.19) enzyme activity that is inhibited by
      cilastatin has been detected in pancreatic zymogen granule membranes of human,
      porcine and rat origin. Immunoelectrophoretic blot analysis of human and porcine
      pancreatic zymogen granule membranes with polyclonal antisera raised against the
      corresponding kidney membrane dipeptidase revealed that the enzyme is a
      disulphide-linked homodimer of subunit mass 61 kDa in the human and 45 kDa in the
      pig. Although membrane dipeptidase was, along with glycoprotein-2, one of the
      only two major components of carbonate high pH-washed membranes, no enzyme
      activity or immunoreactivity was detected in the zymogen granule contents.
      Digestion with bacterial phosphatidylinositol-specific phospholipase C (PI-PLC),
      and subsequent recognition by antibodies specific for the cross-reacting
      determinant, revealed that membrane dipeptidase in human and porcine pancreatic
      zymogen granule membranes is glycosyl-phosphatidylinositol-anchored. Membrane
      dipeptidase was released from the pancreatic zymogen granule membranes by an
      endogenous hydrolase, and the released form migrated as a disulphide-linked dimer
      on SDS/PAGE under non-reducing conditions. Under reducing conditions it migrated
      with the same apparent molecular mass as the membrane-bound form, and was still a
      substrate for bacterial PI-PLC. Treatment of kidney microvillar membranes with
      phospholipase A2 resulted in the release of membrane dipeptidase in a form that
      demonstrated electrophoretic and cilastatin-Sepharose binding properties
      identical to those of the endogenously released form of the enzyme from zymogen
      granule membranes. These results indicate that the glycosyl-phosphatidylinositol
      anchor on the pancreatic membrane dipeptidase is cleaved by an endogenous
      hydrolase, probably a phospholipase A, and that this cleavage may promote the
      release of the protein from the membrane.

PMID- 9164852
TI  - Growth hormone and phorbol esters require specific protein kinase C isoforms to
      activate mitogen-activated protein kinases in 3T3-F442A cells.
AB  - Previous studies have shown that the activation of p44 and p42 mitogen-activated
      protein (MAP) kinases (ERK1 and ERK2) by growth hormone (GH) and phorbol esters,
      but not by epidermal growth factor, in 3T3-F442A preadipocytes is dependent on
      protein kinase C (PKC). In the present study two approaches have been taken to
      determine the PKC isoform dependence of MAP kinase activation in these cells. By
      immunoblotting with specific antibodies, the cells were found to express PKC
      alpha, -gamma,-delta, -epsilon and -zeta. Treatment of cells with 500 nM PMA for
      3 h led to the complete depletion of PKC-delta and the partial depletion of PKC
      alpha but did not significantly affect the expression of the other PKC isoforms.
      In parallel, such treatment severely attenuated the ability of GH to activate MAP
      kinase. The degree of this attenuation was not increased by more prolonged PMA
      pretreatment, indicating that PKC-delta and perhaps PKC-alpha are important for
      MAP kinase activation by GH. These experiments further revealed that additional
      PKC isoforms were required for the full activation of MAP kinases by acute
      treatment with PMA. A second approach involved the use of anti-sense
      oligodeoxynucleotides (ODNs) to deplete the individual PKC isoforms selectively.
      Each of the ODNs used effectively depleted the relevant isoform to undetectable
      levels and did not affect the expression of the other PKC isoforms. Pretreatment
      of cells with PKC-delta anti-sense ODN, but not with anti-sense ODN to the other
      phorbol ester-sensitive isoforms, severely attenuated the activation of MAP
      kinases by GH. PKC-delta anti-sense ODN also blocked (by approx. 50%) the
      activation of MAP kinases by PMA. Furthermore a combination of PKC-delta and 
      epsilon anti-sense ODNs completely blocked the effect of PMA on MAP kinases.
      Collectively, these results indicate that the novel PKC-delta and -epsilon
      isoforms can couple to the MAP kinase pathway in 3T3-F442A cells but that the
      activation of MAP kinases by GH specifically involves PKC-delta.

PMID- 9164854
TI  - Chromosomal organization and expression analysis of two distinct genes encoding
      glutamine/glutamic acid-rich proteins.
AB  - GRP-Ca and GRP-Cb are two genes that encode glutamine/glutamic acid-rich proteins
      of the rat. These genes are very similar in structure and sequence, differing
      only within an approx. 90 bp segment of exon 3. We have used distinct
      oligonucleotide probes to unambiguously distinguish GRP-Ca and GRP-Cb gene
      expression. The two genes are expressed to relatively equivalent levels only in
      the submandibular gland. Chronic daily exposure to the beta-adrenergic agonist,
      isoprenaline, resulted in a statistically significant decrease in GRP-Ca
      expression, with no effect on GRP-Cb, in contrast with previous reports.
      Furthermore it was determined by PCR analysis of both submandibular-gland cDNA
      and genomic DNA that the GRP-Cb gene shows interanimal variability in the number
      of 69 bp tandem repeats found within exon 3; GRP-Cb genes were shown to contain
      four, five or six repeats. GRP-Ca shows no such variability, containing only five
      tandem repeats in all animals examined. The two genes were localized to within
      450 kb of one another at q43-q44 of rat chromosome 4 using somatic cell hybrid
      analysis, pulsed-field gel analysis and fluorescent in situ hybridization.

PMID- 9164853
TI  - Protein kinase C isoenzymes in airway smooth muscle.
AB  - The protein kinase C (PKC) isoenzymes expressed by bovine tracheal smooth muscle
      (BTSM) were identified at the protein and mRNA levels. Western immunoblot
      analyses reliably identified PKCalpha, PKCbetaI and PKCbetaII. In some
      experiments immunoreactive bands corresponding to PKCdelta, PKCepsilon and
      PKCTheta were also labelled, whereas the gamma, eta and zeta isoforms of PKC were
      never detected. Reverse transcriptase PCR of RNA extracted from BTSM using
      oligonucleotide primer pairs designed to recognize unique sequences in the PKC
      genes for which protein was absent or not reproducibly identified by
      immunoblotting, amplified cDNA fragments that corresponded to the predicted sizes
      of PKCdelta, PKCepsilon and PKCzeta, which was confirmed by Southern blotting.
      Anion-exchange chromatography of the soluble fraction of BTSM following
      homogenization in Ca2+-free buffer resolved two major peaks of activity. Using
      epsilon-peptide as the substrate, the first peak of activity was dependent upon
      Ca2+ and 4beta-PDBu (PDBu=phorbol 12, 13-dibutyrate), and represented a mixture
      of PKCs alpha, betaI and betaII. In contrast, the second peak of activity, which
      eluted at much higher ionic strength, also appeared to comprise a combination of
      conventional PKCs that were arbitrarily denoted PKCalpha', PKCbetaI' and
      PKCbetaII'. However, these novel enzymes were cofactor-independent and did not
      bind [3H]PDBu, but were equally sensitive to the PKC inhibitor GF 109203X
      compared with bona fide conventional PKCs, and migrated on SDS/polyacrylamide
      gels as 81 kDa polypeptides. Taken together, these data suggest that PKCs alpha',
      betaI' and betaII' represent modified, but not proteolysed, forms of their
      respective native enzymes that retain antibody immunoreactivity and sensitivity
      to PKC inhibitors, but have lost their sensitivity to Ca2+ and PDBu when epsilon
      peptide is used as the substrate.

PMID- 9164855
TI  - von Willebrand factor binds to native collagen VI primarily via its A1 domain.
AB  - Collagen VI is abundant in the arterial subendothelium. To investigate its
      mechanism of interaction with von Willebrand factor (vWF), collagen VI was
      isolated from human placenta and from the extracellular matrix of the human lung
      fibroblast cell line MRC-5. Purified vWF bound to non-digested collagen VI with
      moderately high affinity (EC50 approximately 5 nM) and could be inhibited by the
      Hirudo medicinalis collagen inhibitor calin. The anti-(human vWF A1 domain)
      monoclonal antibody (AJvW-2), as well as aurin tricarboxylic acid (ATA), at
      concentrations that saturate the vWF A1 domain, also inhibited this binding. In
      contrast, the monoclonal anti-(human vWF A3 domain) antibody (82D6A3) inhibited
      vWF binding to collagens I, III and IV, but had no effect on vWF binding to
      collagen VI. Likewise, vWF binding to collagen VI was not inhibited by the
      recombinant vWF domain D4. Polyclonal anti-(collagen VI) antibodies, specifically
      neutralizing the binding of vWF to collagen VI, confirmed that in the intact
      endothelial cell extracellular matrix, collagen VI was accessible for interaction
      with vWF. This binding was only marginally affected by 82D6A3 but was dose
      dependently inhibited by AJvW-2, ATA and the A1 domain analogue VCL (recombinant
      A1 domain of vWF), with IC50 values comparable to those found for the inhibition
      of vWF binding to isolated collagen VI. The weak interaction of isolated human
      platelets with collagen VI was mediated via the platelet collagen receptor
      (GPIa/IIa) and was competitively inhibited by vWF but not by VCL, suggesting that
      vWF and GPIa/IIa bind to neighbouring but distinct sites on collagen VI. We
      conclude that vWF binds to collagen VI primarily via its A1 domain, which
      distinguishes it from the vWF A3 domain-mediated binding to fibrillar collagens.

PMID- 9164856
TI  - Rat hepatic glutaminase: identification of the full coding sequence and
      characterization of a functional promoter.
AB  - Glutamine catabolism in mammalian liver is catalysed by a unique isoenzyme of
      phosphate-activated glutaminase. The full coding and 5' untranslated sequence for
      rat hepatic glutaminase was isolated by screening lambda ZAP cDNA libraries and a
      Charon 4a rat genomic library. The sequence produces a mRNA 2225 nt in length,
      encoding a polypeptide of 535 amino acid residues with a calculated molecular
      mass of 59.2 kDa. The deduced amino acid sequence of rat liver glutaminase shows
      86% similarity to that of rat kidney glutaminase and 65% similarity to a putative
      glutaminase from Caenorhabditis elegans. A genomic clone to rat liver glutaminase
      was isolated that contains 3.5 kb of the gene and 7.5 kb of the 5' flanking
      region. The 1 kb immediately upstream of the hepatic glutaminase gene (from -1022
      to +48) showed functional promoter activity in HepG2 hepatoma cells. This
      promoter region did not respond to treatment with cAMP, but was highly responsive
      (10-fold stimulation) to the synthetic glucocorticoid dexamethasone. Subsequent
      5' deletion analysis indicated that the promoter region between -103 and +48 was
      sufficient for basal promoter activity. This region does not contain an
      identifiable TATA element, indicating that transcription of the glutaminase gene
      is driven by a TATA-less promoter. The region responsive to glucocorticoids was
      mapped to -252 to -103 relative to the transcription start site.

PMID- 9164857
TI  - Expression of the calcium-independent cytokine-inducible (iNOS) isoform of nitric
      oxide synthase in rat placenta.
AB  - The presence of the calcium-independent cytokine-inducible nitric oxide synthase
      (iNOS) has been investigated in rat placenta from day 19 of gestation till
      delivery. iNOS has been detected at the mRNA, enzyme activity and protein levels
      in complete placenta. Immunocytochemical detection of iNOS was heterogeneously
      distributed in control placenta. Intraperitoneal injection of pregnant rats at 21
      days of gestation with lipopolysaccharide (LPS) increased the iNOS
      immunoreactivity in the decidua basalis of the placenta, and, when the mRNA
      levels and enzyme activity were measured in total tissue, a moderate increase
      (approx. 160%) was observed. A constitutive nuclear factor kappaB activity was
      observed in placenta from both control and LPS-treated animals. These results
      indicate constitutive expression of iNOS in rat placenta.

PMID- 9164858
TI  - Developmental regulation of mRNA species for types II, IX and XI collagens during
      mouse embryogenesis.
AB  - Several techniques were used to study the co-ordination of mRNA levels for five
      constituent chains of cartilage collagen fibrils during mouse development. Short
      cDNA clones were first constructed for mouse and human alpha3(IX) and for mouse
      proalpha1(XI) collagen mRNA species. Northern analysis of developing mouse
      embryos revealed that the mRNA species for alpha1, alpha2 and alpha3 chains of
      type IX collagen peaked earlier than those for proalpha1(II) and proalpha1(XI)
      collagen chains. Quantification of these mRNA species by slot-blot hybridization
      confirmed this developmental regulation: the mRNA ratios for type II/type IX/type
      XI collagens changed from 5.7:1:0.6 (at embryonic day 12.5) to 10.6:1:0.9 (in
      newborn mice). However, the genes coding for the three chains of type IX collagen
      seemed to be under more co-ordinated regulation during mouse development. In
      addition to high mRNA levels in cartilages and the eye, low levels of type IX
      collagen transcripts were identified in brain and skin of newborn mouse using
      RNase protection and reverse transcriptase-PCR assays. Finally, hybridization in
      situ revealed identical tissue distributions of the three type IX collagen mRNA
      species during early chondrogenesis but somewhat more widespread expression of
      the alpha1(IX) and alpha3(IX) mRNA species during endochondral ossification at
      day 16.5 of embryonic development. These results suggest a relatively tight co
      ordination of the alpha1(IX), alpha2(IX), and alpha3(IX) collagen mRNA species in
      chondrocytes, but a lack of co-ordination in several non-cartilaginous tissues.

PMID- 9164859
TI  - Functional studies in 3T3L1 cells support a role for SNARE proteins in insulin
      stimulation of GLUT4 translocation.
AB  - Insulin stimulation of glucose transport in the major insulin-responsive tissues
      results predominantly from the translocation to the cell surface of a particular
      glucose transporter isoform, GLUT4, residing normally under basal conditions in
      intracellular vesicular structures. Recent studies have identified the presence
      of vesicle-associated membrane protein (VAMP) 2, a protein involved in vesicular
      trafficking in secretory cell types, in the vesicles of insulin-sensitive cells
      that contain GLUT4. The plasma membranes of insulin-responsive cells have also
      been shown to contain syntaxin 4 and the 25 kDa synaptosome-associated protein
      (SNAP-25), two proteins that form a complex with VAMP 2. The potential functional
      involvement of VAMP 2, SNAP-25 and syntaxin 4 in the trafficking of GLUT4 was
      assessed in the present study by determining the effect on GLUT4 translocation of
      microinjection of toxins that specifically cleave VAMPs or SNAP-25, or
      microinjection of specific peptides from VAMP 2 and syntaxin 4. Microinjection of
      tetanus toxin light chain or botulinum D toxin light chain resulted in an 80 and
      61% inhibition respectively of insulin stimulation of GLUT4 translocation in
      3T3L1 cells assessed using the plasma-membrane lawn assay. Botulinum A toxin
      light chain, which cleaves SNAP-25, was without effect. Microinjection of an N
      terminal VAMP 2 peptide (residues 1-26) inhibited insulin stimulation of GLUT4
      translocation by 54%. A syntaxin 4 peptide (residues 106-122) inhibited insulin
      stimulation of GLUT4 translocation by 40% whereas a syntaxin 1c peptide (residues
      226-260) was without effect. These data taken together strongly suggest a role
      for VAMP 2 in GLUT4 trafficking and also for syntaxin 4. They further indicate
      that the isoforms of SNAP-25 isolated to date that are sensitive to cleavage by
      botulinum A toxin light chain do not appear to be involved in GLUT4
      translocation.

PMID- 9164860
TI  - Two distinct uptake mechanisms for ascorbate and dehydroascorbate in human
      lymphoblasts and their interaction with glucose.
AB  - In diabetes, a major cause of mortality is from cardiovascular causes, and low
      levels of antioxidants such as vitamin C have been associated with such
      complications. Leucocyte ascorbic acid status can reflect total body stores but
      the mechanisms that mediate the uptake of ascorbic acid (AA) or dehydroascorbic
      acid (DHA) in human lymphoid cells are undefined. We have investigated the uptake
      of AA and DHA with mass assays in human lymphoblasts by using HPLC, with
      precautions to prevent the oxidation of AA and to take into account the
      instability of DHA in buffers. Human lymphoblasts exhibit distinct uptake
      mechanisms for both AA and DHA, with Vmax values of 1.35+/-0.14 and 29.0+/-5.8
      nmol/h per 10(6) cells and Km values of 23.5+/-6 and 104+/-84 microM
      respectively. The AA uptake was Na+-dependent and inhibitable with ouabain,
      whereas DHA uptake was independent of Na+ and ouabain-insensitive. Both uptake
      mechanisms were inhibited by phloretin or cytochalasin B. AA uptake was decreased
      significantly (by 13+/-2%) only at extracellular glucose concentrations of 20 mM
      (P<0.05). In contrast, glucose competitively inhibited DHA uptake with a Ki of
      2.2 mM so that DHA uptake was decreased by glucose even in the physiological
      range. Phorbol esters stimulated AA but not DHA uptake; this was abolished in the
      presence of extracellular reductant, indicating that AA was converted to DHA
      before uptake occurred. Prolonged increased glucose levels (20 mM) led to a
      decrease in the Vmax of DHA uptake. At concentrations of plasma AA or DHA, the AA
      uptake mechanism might be nearly half-saturated but the DHA mechanism has
      enormous spare capacity. This allows for cellular uptake and regeneration of AA
      from DHA derived from oxidative stress. In diabetes, high glucose levels might
      impair DHA uptake acutely by competitive inhibition or by down-regulation of
      uptake with chronic glucose exposure, leading to an impaired ability to store and
      recycle oxidized AA.

PMID- 9164861
TI  - Prolactin stimulates the JAK2 and focal adhesion kinase pathways in human breast
      carcinoma T47-D cells.
AB  - Treatment of T47-D human breast carcinoma cells with recombinant prolactin
      (rhPRL) induced a concentration- and time-dependent increase in the
      phosphotyrosine content of JAK2. rhPRL also stimulated JAK2 tyrosine
      phosphorylation more weakly in three other breast carcinoma lines, MCF-7, ZR-75-1
      and MDA-MB-231. Furthermore it stimulated tyrosine phosphorylation of two
      isoforms of the transcriptional activator STAT5, STAT5a and STAT5b. Surprisingly,
      rhPRL treatment of T47-D cells also stimulated tyrosine phosphorylation of focal
      adhesion kinase (FAK), as determined by immunoprecipitation with anti
      phosphotyrosine antibody followed by immunoblotting with a specific FAK antibody.
      The effect of rhPRL was rapid and concentration-dependent, being maximal at 5
      ng/ml. At rhPRL concentrations above 25 ng/ml, FAK tyrosine phosphorylation
      declined but remained above control levels at 100 ng/ml. rhPRL also stimulated
      paxillin tyrosine phosphorylation in T47-D cells with similar concentration- and
      time-dependence. In a second human breast carcinoma cell line, MCF-7, rhPRL
      produced very similar effects on FAK and paxillin tyrosine phosphorylation. These
      findings identify a new protein tyrosine kinase pathway in the action of the
      lactogenic hormone rhPRL and represent the first report that a hormone acting
      through a member of the haemopoietin receptor superfamily can regulate the
      FAK/paxillin pathway.

PMID- 9164862
TI  - NF-kappaB-dependent expression of nitric oxide synthase is required for membrane
      fusion of chick embryonic myoblasts.
AB  - The activity of nitric oxide synthase (NOS) has recently been shown to increase
      transiently but dramatically in chick embryonic myoblasts that are competent for
      fusion and that NO acts as a messenger for the cell fusion. Here we show that the
      rise in NOS activity is tightly correlated with an increase in NOS protein level,
      and its synthesis is under transcriptional control. In addition, a partial cDNA
      sequence of NOS obtained by reverse transcription PCR on total RNA from chick
      myoblasts was found to be identical with that of the inducible type of NOS (iNOS)
      from chick macrophage. Thus chick myoblast NOS must belong to the family of iNOS.
      Consistently, pyrrolidine dithiocarbamate, a potent inhibitor of nuclear factor
      kappaB (NF-kappaB), prevented the expression of myoblast NOS. Furthermore the
      antioxidant also strongly inhibited cell fusion, and its inhibitory effect was
      reversed by treatment with sodium nitroprusside, an NO-generating agent. In
      addition, nuclear extracts obtained from myoblasts that were competent for
      fusion, but not those from proliferating cells or from fully differentiated
      myotubes, were capable of binding to the consensus NF-kappaB site in the promoter
      region of the gene encoding iNOS. These results suggest that NF-kappaB-dependent
      expression of NOS is an important step in membrane fusion of chick embryonic
      myoblasts.

PMID- 9164863
TI  - Glutathione S-transferases from the white-rot fungus, Phanerochaete
      chrysosporium.
AB  - A glutathione S-transferase (GST) was purified to homogeneity from the white-rot
      fungus, Phanerochaete chrysosporium, by affinity chromatography on glutathione
      agarose followed by Mono-Q ion-exchange FPLC. This protein immunoblotted with
      antisera to rat Theta class GST 5-5 and also showed N-terminal sequence
      similarity to the Theta class, including the presence of a conserved serine
      residue that has been specifically implicated in catalysis in this class [Wilce,
      Board, Feil and Parker (1995) EMBO J. 14, 2133-2143] and other residues conserved
      in plant sequences. Catalytic activity was found to be highly labile in the
      purified protein, although preliminary evidence for activity (approx. 120 m
      units/mg) with 1,2-epoxy-3-(p-nitrophenoxy)propane was obtained in some
      preparations. The enzyme seems to be a dimer with a subunit molecular mass of 25
      kDa by SDS/PAGE. The native molecular masses estimated by non-denaturing
      electrophoresis and by Superose-12 gel filtration were 58 and 45 kDa
      respectively. A second protein purified in this study also gave low level of
      activity with 1,2-epoxy-3-(p-nitrophenoxy)propane and had a subunit molecular
      mass of 28 kDa (native size 62-63 kDa), but did not immunoblot with any GST class
      and seemed to be N-terminally blocked.

PMID- 9164865
TI  - Mapping of contact sites in the caldesmon-calmodulin complex.
AB  - The interaction of intact calmodulin and its four tryptic peptides with deletion
      mutants of caldesmon was analysed by native gel electrophoresis, fluorescence
      spectroscopy and zero-length cross-linking. Deletion mutants H2 (containing
      calmodulin-binding sites A and B) and H9 (containing sites B and B') interacted
      with intact calmodulin to form complexes whose stoichiometries varied from 2:1 to
      1:1. The N-terminal peptides of calmodulin (TR1C, residues 1-77, and TR2E,
      residues 1-90) bound H2 with higher affinity than H9. At the same time H2 was
      less effective than H9 in binding to the C-terminal peptides of calmodulin TR2C
      (residues 78-148) and TR3E (residues 107-148). The N-terminal peptides of
      calmodulin (TR1C and TR2E) could be cross-linked to intact caldesmon and its
      deletion mutants H2 and H9. The similarity in the primary structures of sites A
      and B' of caldesmon and our measurements of the affinities of H2 and H9 to
      calmodulin and its peptides strongly indicate an orientation of the protein
      complex where sites A and B' interact with the N-terminal domain of calmodulin,
      whereas site B interacts with the C-terminal domain of calmodulin. The spatial
      organization of contact sites in the caldesmon-calmodulin complex agrees with the
      earlier proposed two-dimensional model of interaction of the two proteins [Huber,
      El-Mezgueldi, Grabarek, Slatter, Levine and Marston (1996) Biochem. J. 316, 413
      420].

PMID- 9164864
TI  - TFIIF, a basal eukaryotic transcription factor, is a substrate for poly(ADP
      ribosyl)ation.
AB  - We have examined the susceptibility of some of the basal eukaryotic transcription
      factors as covalent targets for poly(ADP-ribosyl)ation. Human recombinant TATA
      binding protein, transcription factor (TF)IIB and TFIIF (made up of the 30 and 74
      kDa RNA polymerase II-associated proteins RAP30 and RAP74) were incubated with
      calf thymus poly(ADP-ribose) polymerase and [32P]NAD+ at 37 degrees C. On lithium
      dodecyl sulphate/PAGE and autoradiography, two bands of radioactivity, coincident
      with RAP30 and RAP74, were observed. No radioactivity co-migrated with TATA
      binding protein or TFIIB. The phenomenon was dependent on the presence of nicked
      DNA, which is essential for poly(ADP-ribose) polymerase activity. Covalent
      modification of TFIIF increased with time of incubation, with increasing TFIIF
      concentration and with increasing NAD+ concentration. High-resolution PAGE
      confirmed that the radioactive species associated with RAP30 and RAP74 were ADP
      ribose polymers. From these observations, we conclude that both TFIIF subunits
      are highly specific substrates for covalent poly(ADP-ribosyl)ation.

PMID- 9164866
TI  - Identification of the cleavage sites in the alpha6A integrin subunit: structural
      requirements for cleavage and functional analysis of the uncleaved alpha6Abeta1
      integrin.
AB  - The alpha6A and alpha6B integrin subunits are proteolytically cleaved during
      biosynthesis into a heavy chain (120 kDa) that is disulphide-linked to one of two
      light chains (31 or 30 kDa). Analysis of the structure of the alpha6A subunit on
      the carcinoma cell line T24 and human platelets demonstrated that the two light
      chains of alpha6 are not differentially glycosylated products of one polypeptide.
      Rather they possess different polypeptide backbones, which presumably result from
      proteolytic cleavage at distinct sites in the alpha6 precursor. Mutations were
      introduced in the codons for the R876KKR879, E883K884, R890K891 and R898K899
      sequences, the potential proteolytic cleavage sites, and wild-type and mutant
      alpha6A cDNAs were transfected into K562 cells. The mutant alpha6A integrin
      subunits were expressed in association with endogenous beta1 at levels comparable
      to that of wild-type alpha6Abeta1. A single alpha6 polypeptide chain (150 kDa)
      was precipitated from transfectants expressing alpha6A with mutations or
      deletions in the RKKR sequence. Mutations in the EK sequence yielded alpha6A
      subunits that were cleaved once into a heavy and a light chain, whereas alpha6A
      subunits with mutations in one of the two RK sequences were, like wild-type
      alpha6A, cleaved into one heavy and two light chains. Thus a change in the RKKR
      sequence prevents the cleavage of alpha6. The EK site is the secondary cleavage
      site, which is used only when the primary site (RKKR) is intact. Microsequencing
      of the N-termini of the two alpha6A light chains from platelets demonstrated that
      cleavage occurs after Arg879 and Lys884. Because alpha6(RKKG), alpha6(GKKR) and
      alpha6(RGGR) subunits were not cleaved it seems that both the arginine residues
      and the lysine residues are essential for cleavage of RKKR. alpha6A mutants with
      the RKKR sequence shifted to the EK site, in such a way that the position of the
      arginine residue after which cleavage occurs corresponds exactly to Lys884, were
      partly cleaved, whereas alpha6A mutants with the RKKR sequence shifted to other
      positions in the alpha6A subunit, including one in which it was shifted two
      residues farther than the EK cleavage site, were not cleaved. In addition,
      alpha6A mutants with an alpha5-like cleavage site, i.e. arginine, lysine and
      histidine residues at positions -1, -2 and -6, were not cleaved. Thus both an
      intact RKKR sequence and its proper position are essential. After activation by
      the anti-beta1 stimulatory monoclonal antibody TS2/16, both cleaved and uncleaved
      alpha6Abeta1 integrins bound to laminin-1. The phorbol ester PMA, which activates
      cleaved wild-type and mutant alpha6Abeta1, did not activate uncleaved
      alpha6Abeta1. Thus uncleaved alpha6Abeta1 is capable of ligand binding, but not
      of inside-out signalling. Our results suggest that cleavage of alpha6 is required
      to generate a proper conformation that enables the affinity modulation of the
      alpha6Abeta1 receptor by PMA.

PMID- 9164867
TI  - Biochemical characteristics of a rice (Oryza sativa L., IR36) G-protein alpha
      subunit expressed in Escherichia coli.
AB  - A cDNA encoding the alpha-subunit of the heterotrimeric G-protein in rice (RGA1)
      was overexpressed in Escherichia coli and then isolated by Ni2+-nitrilotriacetic
      acid affinity chromatography. The molecular mass of RGA1 bearing a His tag was
      approx. 49 kDa. Immunoblot analysis using anti-RGA1 revealed that the RGA1
      protein is most abundant in seedling leaves and least abundant in mature roots.
      It exists at particularly high levels in the immature embryo after pellicle
      extrusion. In addition, the RGA1 antiserum exhibited a difference in binding
      affinity for Galpha proteins from monocots (maize and rice) and dicots
      (Arabidopsis, pea, soya bean and tomato); whereas it cross-reacted with Galpha
      proteins of monocots, it did not with those of dicot plants. When bound to
      guanosine 5'-(gamma-thio)triphosphate (GTP[S]), the RGA1 protein was partially
      protected from tryptic proteolysis. In the presence of GTP[S], trypsin cleaved
      the RGA1 protein into four fragments 24, 14, 11 and 5 kDa in size. When RGA1 was
      bound to GDP, only the 5 kDa polypeptide was seen on SDS/PAGE after trypsin
      digestion. Photoaffinity labelling with [alpha-32P]GTP and a GTP[S]-binding assay
      revealed that RGA1 incorporated 32P and showed specific binding to a guanine
      nucleotide. Guanidine binding of RGA1 was affected by the concentration of MgCl2
      (maximum at 2 mM). The rate of guanine nucleotide binding of RGA1
      (kon,GTP[S]=0.0141+/-0.0014 min-1) and, at steady state, the kcat value for GTP
      hydrolysis (0.0075+/-0.0001 min-1) were very low even at 2 mM MgCl2. The binding
      affinity for the nucleotides examined was in the order GTP-S- >/= GTP > GDP > CTP
      > ATP >/= dTTP.

PMID- 9164868
TI  - Thrombin activation of human platelets dissociates a complex containing gelsolin
      and actin from phosphatidylinositide-specific phospholipase Cgamma1.
AB  - We have examined the association of two cytoskeleton proteins, gelsolin and
      actin, with phosphatidylinositide-specific phospholipase Cgamma1 (PLCgamma1) in
      resting and thrombin-stimulated human platelets. In unstimulated platelets,
      gelsolin, actin and PLCgamma1 were immunoprecipitated as a complex by a
      polyclonal antibody to PLCgamma1. The association of gelsolin and actin was
      specific for PLCgamma1 because immunoprecipitates of PLCs beta2, beta3, gamma2
      and delta1, which are also expressed in human platelets, did not contain
      detectable gelsolin or actin. Activation with thrombin resulted in platelet
      aggregation and the dissociation of gelsolin and actin from PLCgamma1. Inhibition
      of thrombin-induced platelet aggregation blocked the dissociation of gelsolin and
      actin from PLCgamma1. After stimulation with thrombin, PLCgamma1 activity in
      immunoprecipitates was increased 2-3-fold. This elevation in PLCgamma1 activity
      in response to thrombin activation was not observed when platelet aggregation was
      blocked. Although PLCgamma1 is tyrosine phosphorylated in response to many
      agonists, we could not detect, by Western analysis with anti-phosphotyrosine
      antibodies, tyrosine phosphorylation of PLCgamma1 immunoprecipitated from
      thrombin-stimulated platelets. These results demonstrate that PLCgamma1 is
      associated with gelsolin and actin in resting platelets, and that thrombin
      induced platelet aggregation results in the dissociation of PLCgamma1 from
      gelsolin and actin, and the stimulation of PLCgamma1 activity.

PMID- 9164869
TI  - Tissue-specific regulation of medium-chain acyl-CoA dehydrogenase gene by thyroid
      hormones in the developing rat.
AB  - During development, gene expression of medium-chain acyl-CoA dehydrogenase
      (MCAD), a nuclear-encoded mitochondrial enzyme that catalyses the first step of
      medium-chain fatty acid beta-oxidation, is highly regulated in tissues in
      accordance with fatty acid utilization, but the factors involved in this
      regulation are largely unknown. To investigate a possible role of thyroid
      hormones, rat pups were made hypothyroid by the administration of
      propylthiouracyl to the mother from day 12 of gestation, and their kidneys, heart
      and liver were removed on postnatal day 16 to determine MCAD mRNA abundance,
      protein level and enzyme activity. Similar experiments were run in 3,3',5-tri
      iodothyronine (T3)-replaced hypothyroid (1 microg of T3/100 g body weight from
      postnatal day 5 to 15) and euthyroid pups. Hypothyroidism led to an increase in
      MCAD mRNA abundance in kidney and a decrease in abundance in heart, but had no
      effect in liver. The protein levels and enzyme activity were lowered in
      hypothyroid heart and kidney, suggesting that hypothyroidism affects post
      transcriptional steps of gene expression in the kidney. All the effects of
      hypothyroidism were completely reversed in both heart and kidney by T3
      replacement. Injection of a single T3 dose into 16-day-old euthyroid rats also
      led to tissue-specific changes in mRNA abundance. Nuclear run-on assays performed
      from hypothyroid and hypothyroid plus T3 rats showed that T3 stimulates MCAD gene
      transcription in heart and represses it in the kidney. These results indicate
      that the postnatal rise in circulating T3 is essential to the developmental
      regulation of the MCAD gene in vivo.

PMID- 9164870
TI  - Molecular cloning of a major human gall bladder mucin: complete C-terminal
      sequence and genomic organization of MUC5B.
AB  - Gall bladder mucin has been shown to play a central role in the pathogenesis of
      cholesterol gallstone disease. While cloning and sequencing studies have provided
      a wealth of information on the structure of other gastrointestinal and
      respiratory mucins, nothing is known about the primary structure of human gall
      bladder mucin. In this study, we show that the tracheobronchial mucin MUC5B is a
      major mucin gene product expressed in the gall bladder. Antibodies directed
      against deglycosylated human gall bladder mucin were used to screen a gall
      bladder cDNA expression library, and most of the isolated clones contained
      repetitive sequences nearly identical with those in the tandem repeat region of
      MUC5B. An additional clone (hGBM2-3) contained an open reading frame coding for a
      389 residue cysteine-rich sequence. The arrangement of cysteine residues in this
      sequence was very similar to that in the C-terminal regions of MUC2, MUC5AC and
      human von Willebrand factor. This cysteine-rich sequence was connected to a
      series of degenerate MUC5B tandem repeats in a 7.5 kb HincII genomic DNA
      fragment. This fragment, with ten exons and nine introns, contained MUC5B repeats
      in exon 1 and a 469 residue cysteine-rich sequence in exons 2-10 that provided a
      152 nucleotide overlap with cDNA clone hGBM2-3. Interestingly, the exon-intron
      junctions in the MUC5B genomic fragment occurred at positions equivalent to those
      in the D4 domain of human von Willebrand factor, suggesting that these proteins
      evolved from a common evolutionary ancestor through addition or deletion of exons
      encoding functional domains.

PMID- 9164871
TI  - Nitric oxide inhibits the synthesis of type-II collagen without altering Col2A1
      mRNA abundance: prolyl hydroxylase as a possible target.
AB  - The addition of human recombinant interleukin-1beta (IL-1beta) to cultures of
      lapine articular chondrocytes provoked the synthesis of large amounts of NO and
      reduced the production of type-II collagen. NG-Monomethyl-l-arginine (L-NMA), an
      inhibitor of NO synthase, strongly suppressed the production of NO and partially
      relieved the inhibition of collagen synthesis in response to IL-1beta. The NO
      donor S-nitrosoacetylpenicillamine (SNAP), on the other hand, inhibited collagen
      production. IL-1 lowered the abundance of Col2A1 mRNA in an NO-independent
      manner. Collectively, these data indicate that IL-1 suppresses collagen synthesis
      at two levels: a pretranslational level which is NO-independent, and a
      translational or post-translational level which is NO-mediated. These effects are
      presumably specific as L-NMA and SNAP had no effect on total protein synthesis or
      on the distribution of newly synthesized proteins between the cellular and
      extracellular compartments. Prolyl hydroxylase is an important enzyme in the post
      translational processing of collagen, and its regulation and cofactor
      requirements suggest possible sensitivity to NO. Extracts of cells treated with
      IL-1 or SNAP had lower prolyl hydroxylase activity, and L-NMA was partially able
      to reverse the effects of IL-1. These data suggest that prolyl hydroxylase might
      indeed be a target for NO. Because underhydroxylated collagen monomers fail to
      anneal into stable triple helices, they are degraded intracellularly. Inhibition
      of prolyl hydroxylase by NO might thus account for the suppressive effect of this
      radical on collagen synthesis.

PMID- 9164872
TI  - Differential modulation of cell adhesion by interaction between adhesive and
      counter-adhesive proteins: characterization of the binding of vitronectin to
      osteonectin (BM40, SPARC).
AB  - Heparin-binding forms of vitronectin, a multifunctional adhesive glycoprotein,
      are associated with the extracellular matrix (ECM) at different locations in the
      body and serve to promote cell adhesion and the regulation of pericellular
      proteolysis at sites of angiogenesis. In the present study we characterized the
      interactions of vitronectin with the counter-adhesive protein osteonectin (also
      termed SPARC or BM40). Osteonectin and vitronectin were both found associated
      with the ECM of cultured endothelial cells and were localized in vessel wall
      sections of kidney tissue. In vitro, the heparin-binding multimeric isoform of
      vitronectin bound to immobilized osteonectin in a saturable manner with half
      maximal binding at 30-40 nM. Preincubation of plasma vitronectin with plasminogen
      activator inhibitor 1 (PAI-1), which provoked multimer formation, induced the
      binding of vitronectin to osteonectin. Binding was optimal at physiological ionic
      strength, and binary complexes were stabilized by tissue transglutaminase
      mediated cross-linking. In a concentration-dependent fashion, PAI-1, CaCl2,
      heparin and heparan sulphate, but not other glycosaminoglycans, interfered with
      the binding of vitronectin to osteonectin. Using vitronectin-derived synthetic
      peptides as well as mutant forms of recombinant osteonectin, we found that the
      heparin-binding region of vitronectin interacted with the C-terminal region of
      osteonectin that contains a high-affinity Ca2+-binding site with counter-adhesive
      properties. Adhesion of cultured endothelial cells was partly abrogated by
      osteonectin and was correspondingly reversed by vitronectin in a concentration
      dependent manner. These results indicate that specific interactions between
      vitronectin and osteonectin modulate cell adhesion and might thereby regulate
      endothelial cell function during angiogenesis.

PMID- 9164873
TI  - Recombinant human O6-alkylguanine-DNA alkyltransferase (AGT), Cys145-alkylated
      AGT and Cys145 --> Met145 mutant AGT: comparison by isoelectric focusing, CD and
      time-resolved fluorescence spectroscopy.
AB  - Isoelectric focusing, CD, steady-state and time-resolved fluorescence
      spectroscopy were used to compare the native recombinant human DNA-repair protein
      O6-alkylguanine-DNA alkyltransferase (AGT) with AGT derivatives methylated or
      benzylated on Cys145 or modified by site-directed mutagenesis at the active
      centre (Met145 mutant). The AGT protein is approximately spherical with highly
      constrained Trp residues, but is not stabilized by disulphide bridges. In
      contrast with native AGT, alkylated AGT precipitated at 25 degrees C but remained
      monomeric at 4 degrees C. As revealed by isoelectric focusing, pI changed from
      8.2 (AGT) to 8. 4 (Cys145-methylated AGT) and 8.6 (Cys145-benzylated AGT). The
      alpha-helical content of the Met145 mutant was decreased by approx. 5% and Trp
      residues were partially liberated. Although non-covalent binding of O6
      benzylguanine did not alter the secondary structure of AGT, its alpha-helical
      content was increased by approx. 2% on methylation and by approx. 4% on
      benzylation, altogether indicating a small conformational change in AGT on
      undergoing alkylation. No signal sequences have been found in AGT that mark it
      for polyubiquitination. Therefore the signal for AGT degradation remains to be
      discovered.

PMID- 9164875
TI  - Effect of temperature on the secondary structure of beta-lactoglobulin at pH 6.7,
      as determined by CD and IR spectroscopy: a test of the molten globule hypothesis.
AB  - Previous CD measurements of changes in the conformation of beta-lactoglobulin at
      neutral pH as a function of temperature indicated the formation of a molten
      globule state above approx. 70 degrees C. New CD measurements are reported at
      temperatures up to 80 degrees C with an instrument on the Daresbury synchrotron
      radiation source which gives spectra of good signal-to-noise ratio down to 170
      nm. IR spectra were recorded up to 94.8 degrees C with a ZnSe circle cell and a
      single simplified model of the substructure of the amide I' band was used to give
      the fractional contents of beta-sheet structure unambiguously and independently
      of the CD spectroscopy. The results of both techniques, however, were in
      agreement in showing a progressive loss of beta-sheet structure with increasing
      temperature, beginning below the denaturation temperature. Nevertheless, the CD
      spectroscopy showed a fairly abrupt loss of virtually all the helical
      conformation at approx. 65 degrees C. Comparison of the present results with
      other studies on the molten globule formed at acid pH in the lipocalin family
      suggests that above 65 degrees C a partly unfolded state is formed, possibly by
      destabilization of the intermolecular beta-strand I and the loss of the main
      helix, but it is not a classical molten globule transition.

PMID- 9164874
TI  - Molecular cloning and expression of the Candida albicans TOP2 gene allows study
      of fungal DNA topoisomerase II inhibitors in yeast.
AB  - Candida albicans topoisomerase II, encoded by the TOP2 gene, mediates chromosome
      segregation by a double-strand DNA break mechanism and is a potential target for
      anti-fungal therapy. In this paper, we report the characterization of the C.
      albicans TOP2 gene and its use to develop a yeast system that allows the
      identification and study of anti-fungal topoisomerase II inhibitors in vivo. The
      gene, specifying a 1461-residue polypeptide with only 40% identity with human
      topoisomerase IIalpha and beta isoforms, was isolated from C. albicans on a 6.3
      kb EcoRI fragment that mapped to chromosome 4. It was used to construct a plasmid
      in which TOP2 expresses a recombinant enzyme (residues 57-1461 of C. albicans
      topoisomerase II fused to the first five residues of Saccharomyces cerevisiae
      topoisomerase II) under the control of a galactose-inducible promoter. The
      plasmid rescued the lethal phenotype of a temperature-sensitive S. cerevisiae DNA
      topoisomerase II mutant allowing growth at 35 degrees C. Yeast cells, bearing
      ISE2 permeability and rad52 double-strand-break-repair mutations the growth of
      which at 35 degrees C was dependent on C. albicans topoisomerase II, were killed
      by the known topoisomerase II inhibitors amsacrine and doxorubicin. Parallel
      experiments in yeast expressing human topoisomerase IIalpha allowed the relative
      sensitivities of the fungal and host topoisomerases to be examined in the same
      genetic background. To compare the killing in vivo with drug inhibition in vitro,
      the recombinant C. albicans topoisomerase II protein was expressed and purified
      to near-homogeneity from S. cerevisiae yielding a 160 kDa polypeptide that
      displayed the expected ATP-dependent DNA-relaxation and DNA-decatenation
      activities. The enzyme, whether examined in vitro or complementing in S.
      cerevisiae, was comparably sensitive to amsacrine and doxorubicin. Our results
      suggest that potential topoisomerase II-targeting anti-fungal inhibitors can be
      identified and studied in S. cerevisiae.

PMID- 9164876
TI  - Chemoattractants induce tyrosine phosphorylation of ERK2 in Dictyostelium
      discoideum by diverse signalling pathways.
AB  - Two homologues of mitogen-activated protein kinases have been identified in
      Dictyostelium discoideum (ERK1 and EKR2). We here demonstrate transient tyrosine
      phosphorylation of ERK2 in response to the chemoattractants cAMP and folic acid
      that correlates with activity. To investigate the signalling pathways, we studied
      the response in strains with altered cAMP-dependent protein kinase (PKA) status.
      The degree of cAMP-induced ERK2 tyrosine phosphorylation was increased in cells
      overexpressing PKA activity but no such increase was observed in the response to
      folic acid. Our observations suggest that cAMP-induced ERK2 tyrosine
      phosphorylation is positively modulated by a PKA-regulated step which is not
      involved in the response to folic acid, suggesting the presence of diverse
      signalling pathways leading to ERK2 activation.

PMID- 9164877
TI  - Effect of continuous quality improvement analysis on the delivery of primary
      percutaneous transluminal coronary angioplasty for acute myocardial infarction.
AB  - A successful primary percutaneous transluminal coronary angioplasty (PTCA)
      program requires a learning process whereby the efficiency of the cardiac
      catheterization laboratory to deliver prompt intervention can be refined. The
      purpose of this study was to (1) quantify this learning process in terms of
      shortening the time to reperfusion, (2) examine the changes in strategy that
      allowed for this, and (3) determine if expedited reperfusion by primary PTCA
      improved patient outcomes. A database of all primary PTCA procedures was
      established in February 1, 1994. Continuous quality assurance analysis was
      performed, and program modifications introduced as needed. Patients were
      separated into early (group A = February 1, 1994 through January 31, 1995) and
      late (group B1 = February 1, 1995 through June 31, 1995, and group B2 = July 1,
      1995 through December 31, 1995) cohorts. Time intervals to certain treatment
      landmarks were compared among groups. In-hospital outcomes were tabulated. Fifty
      two consecutive patients were included (group A = 19, group B1 = 17, group B2 =
      16). Time intervals shortened significantly (group A vs group B1 vs group B2)
      with the time from hospital presentation to first balloon inflation decreasing
      progressively (from 205 to 119 to 97 minutes; p <0.001). Most of this decrease
      was obtained by shortening the time from hospital presentation to xylocaine
      administration (158 to 85 to 72 minutes; p <0.005), although the time from
      xylocaine to first balloon inflation also decreased (from 47 to 33 to 24 minutes;
      p <0.005). Parallel decreases for in-hospital mortality (26% vs 0%; p = 0.004),
      adverse events (47% vs 18%; p = 0.05), and length of hospital stay (13.3 +/- 13.7
      vs 8.4 +/- 4.4 days; p = NS) were demonstrated for groups A versus B1 and B2. A
      learning effect following initiation of a primary PTCA program is demonstrated in
      which reperfusion was more rapidly achieved as the result of procedural changes
      directed by quality improvement analysis with a concurrent improvement in in
      hospital outcomes.

PMID- 9164878
TI  - Prognostic value of Doppler transmitral flow velocity patterns in acute
      myocardial infarction.
AB  - Doppler transmitral flow patterns are partially dependent on age. We investigated
      the correlations between the age-adjusted transmitral flow patterns, hemodynamic
      indexes, and the coronary and clinical outcome in 206 patients with acute
      myocardial infarction (AMI) and 102 normal control subjects. The peak flow
      velocity at atrial contraction was significantly lower in 50 of the 206 patients
      (24%) (low-A group) than in the 102 normal controls. Pulmonary capillary wedge
      pressure was significantly higher in the low-A group than in the remaining 156
      patients with AMI (20 +/- 7 vs 11 +/- 5 mm Hg, p <0.001), and the cardiac index
      and left ventricular ejection fraction were significantly lower (2.2 +/- 0.6 vs
      2.9 +/- 0.7 L/min/m2, p <0.001; 38 +/- 15% vs 52 +/- 13%, p <0.001). The
      incidence of cardiogenic shock was significantly higher in the low-A group than
      in the other patients with AMI (42% vs 19%, p <0.001). Regression analysis
      demonstrated a significant association between decreased atrial filling velocity
      and increased in-hospital mortality as well as the incidence of heart failure in
      AMI (p <0.001). The 5-year mortality rate was also significantly higher in the
      low-A group (p <0.001). The age-adjusted transmitral flow pattern in AMI can
      identify patients with left ventricular dysfunction, which can lead to a poor
      prognosis.

PMID- 9164880
TI  - Cardiac autonomic function and sensitivity to pain in postmenopausal women with
      angina and normal coronary arteries.
AB  - An increased sensitivity to painful stimuli and an abnormal cardiac autonomic
      function have previously been reported in patients with angina and
      angiographically normal coronary arteries, a syndrome that mainly affects
      postmenopausal women. In this study we compared both general sensitivity to pain,
      by evaluating time to forearm ischemic pain (FIP) provoked by sphygmomanometer
      cuff inflation, and cardiac autonomic function, by measuring heart rate
      variability (HRV), and QT and QT(c) intervals on 24-hour Holter recordings, in 25
      postmenopausal women with angina and normal coronary arteries and in 22 healthy
      postmenopausal women. Compared with controls, patients had a reproducible
      strikingly lower time to FIP (149 +/- 121 vs 295 +/- 158 seconds, p <0.001),
      whereas there were no differences between the 2 groups in HRV variables and mean
      24-hour QT and QT(c) intervals. HRV indexes, and QT and QT(c) intervals also
      showed similar circadian patterns. Thus, our data show that postmenopausal women
      with angina and normal coronary arteries have an enhanced sensitivity to systemic
      painful stimuli, but no detectable impairment in cardiac autonomic function
      compared with a well-matched control group of postmenopausal healthy women.

PMID- 9164879
TI  - Correlates of unrecognized acute myocardial infarction detected via perfusion
      imaging.
AB  - Research using the electrocardiogram (ECG) indicates that about 1/3 of acute
      myocardial infarctions (AMIs) are unrecognized. To date, no studies of
      unrecognized AMIs have employed perfusion imaging, although it is more sensitive
      than the ECG and provides more information about infarct characteristics, such as
      size and location. In this study, 82 of 258 consecutive patients (31.8%)
      undergoing exercise testing with technetium-99m sestamibi perfusion imaging had
      fixed, nonartifactual perfusion defects, suggesting AMI. These patients were
      interviewed regarding their recognition of AMI; 27 patients (32.9%) had
      unrecognized AMI. Unrecognized AMI was significantly associated with (1) smaller
      infarcts, (2) infarcts not in the apical or septal regions, (3) diabetes
      mellitus, (4) lack of angina, (5) a negative family history for cardiac disease,
      and (6) being African-American. Many of these variables were significantly
      intercorrelated, and in multivariate analysis, unrecognized AMI remained
      significantly predicted by a smaller infarct and lack of angina. This study
      suggests that the incidence of unrecognized AMI detected via perfusion imaging on
      a clinic population is similar to that detected via electrocardiographic studies
      on community samples. This study also replicates prior findings of the medical
      history and demographic correlates of unrecognized AMI, and indicates that
      infarct size and location are also associated with unrecognized AMI.

PMID- 9164881
TI  - Mortality benefit of implantable cardioverter-defibrillator therapy in patients
      with persistent malignant ventricular arrhythmias despite amiodarone treatment.
AB  - Implantable cardioverter defibrillators (ICDs) are very effective in preventing
      sudden cardiac death. However, debate continues as to whether ICD implantation is
      superior to amiodarone in prolonging survival in patients with life-threatening
      ventricular arrhythmias. Of 442 consecutive patients treated with amiodarone, we
      identified 48 patients with symptomatic ventricular arrhythmias who met all of
      the following inclusion criteria: (1) had inducible sustained ventricular
      tachycardia at baseline electrophysiologic study, (2) had an oral amiodarone load
      of at least 10 g over 10 to 14 days, (3) remained inducible with a
      hemodynamically unstable ventricular arrhythmia at follow-up electrophysiologic
      study, and (4) were advised to continue amiodarone therapy and undergo ICD
      implantation. Patients who agreed to undergo ICD implantation (n = 28) had a
      lower ejection fraction (29 +/- 9% vs 40 +/- 12% p <0.005) and were younger (61.0
      +/- 10 vs 69 +/- 7 years, p <0.01) than patients who refused device implantation
      (n = 20). Using a Cox proportional-hazards model, defibrillator therapy was the
      strongest independent predictor of improved survival in patients with an ejection
      fraction < or =40% (RR = 0.42; 95% confidence interval 0.22 to 0.79). Thus,
      patients with depressed ejection fraction and continued inducibility of sustained
      ventricular tachycardia despite oral amiodarone loading have a poor prognosis. In
      such patients, ICDs are associated with a 58% reduction in total cardiac
      mortality.

PMID- 9164882
TI  - Influence of patient characteristics in the selection of patients for
      defibrillator implantation (the AVID Registry). Antiarrhythmics Versus
      Implantable Defibrillators.
AB  - The Antiarrhythmics Versus Implantable Defibrillators (AVID) trial is a
      prospective, randomized study of treatment for life-threatening ventricular
      arrhythmias. Patients who are eligible for the main trial but who are not
      enrolled for any reason are followed in a registry. The objective of the present
      study was to determine whether there are identifiable patient characteristics
      among these registry patients that may influence whether a patient is treated
      with an implantable defibrillator. The 914 patients in the registry were divided
      into 2 groups according to whether the primary treatment was an implantable
      defibrillator. The mean age of defibrillator patients was 60 years, compared with
      65 years in the nondefibrillator group (p <0.001). Only 11.2% of defibrillator
      recipients were minorities, whereas the percentage of minorities in the
      nondefibrillator group was 18.7% (p <0.003). A history of recurrent ventricular
      fibrillation was more likely in the group treated with defibrillators (8.9% vs
      4.4%, p <0.01), whereas a history of atrial fibrillation or diabetes mellitus
      were both significantly more likely in the nondefibrillator group. Among
      defibrillator patients, a higher proportion had ventricular fibrillation as the
      index arrhythmia; patients with ventricular tachycardia were significantly more
      likely to be treated without devices. In this prospective but nonrandomized
      cohort of patients treated for life-threatening ventricular arrhythmias, older
      age, minority status, and comorbidity reduced the chances that a patient would be
      treated with a defibrillator.

PMID- 9164883
TI  - QT interval dispersion in healthy subjects and survivors of sudden cardiac death:
      circadian variation in a twenty-four-hour assessment.
AB  - Twenty-four-hour acquisition of QT dispersion (QTd) from the Holter and the
      circadian variation of QTd were evaluated in 20 survivors of sudden cardiac death
      (SCD), in 20 healthy subjects, and in 14 control patients without a history of
      cardiac arrest who were age, sex, diagnosis and therapy matched to 14 SCD
      patients. Computer-assisted QT measurements were performed on 24-hour Holter
      recordings; each recording was divided into 288 5-minute segments and templates
      representing the average QRST were generated. QTd was calculated as the
      difference between QT intervals in leads V1 and V5 for each template on Holter.
      The 24-hour mean QTd was significantly greater in SCD patients (40 +/- 28 ms)
      than in healthy subjects (20 +/- 10 ms) and control patients (15 +/- 5 ms) (p
      <0.05). There was a circadian variation in QTd with greater values at night (0 to
      6 A.M.) than at daytime (10 A.M. to 4 P.M.) in healthy subjects (25 +/- 13 vs 15
      +/- 8 ms, p <0.001) and control patients (18 +/- 10 vs 12 +/- 4 ms p <0.05),
      whereas in SCD patients there was no significant difference between night and day
      values (45 +/- 31 vs 37 +/- 28 ms, p = NS). It is concluded that QTd measured by
      Holter was greater in SCD patients than in healthy subjects and matched control
      patients during the entire day. QTd has a clear circadian variation in normal
      subjects, whereas this variation is blunted in SCD patients. QTd measured on
      Holter differentiates survivors of cardiac arrest and may be a useful tool for
      risk stratification.

PMID- 9164884
TI  - Circannual variation of malignant ventricular tachyarrhythmias in patients with
      implantable cardioverter-defibrillators and either coronary artery disease or
      idiopathic dilated cardiomyopathy.
AB  - We studied the possible relation between the frequency of ventricular
      tachyarrhythmic events and thermal stress in patients with an implantable
      cardioverter-defibrillator (ICD) living in a locally limited area under
      homogeneous climatic conditions. The frequency of tachyarrhythmic events was
      correlated with the thermal stress level according to the "Klima Michel Model," a
      complete thermophysiologic model that calculates "felt-temperature" values on the
      basis of the outdoor temperature and further meteorologic data. During a mean
      follow-up time of 40 +/- 17 months (range 4 to 72), 761 ventricular
      tachyarrhythmic events occurred in 50 of 138 consecutive ICD recipients. Analysis
      of the monthly felt-temperature levels and the mean circannual variation of the
      registered ventricular arrhythmias suggested that very cold and very hot
      conditions may be associated with an increased frequency of ventricular
      tachyarrhythmias. This finding was confirmed by calculation of the sum of
      tachyarrhythmias on all 2,039 days of the follow-up period divided into 5-degree
      step felt-temperature classes. Thus, thermal stress may be 1 factor triggering
      the occurrence of ventricular tachyarrhythmias in patients with cardiac disease
      and suppressed cardiac function. Part of the increase in cardiac mortality under
      above-average hot and cold atmospheric conditions may be attributed to
      ventricular arrhythmic events.

PMID- 9164885
TI  - Atrial fibrillation follow-up investigation of rhythm management -- the AFFIRM
      study design. The Planning and Steering Committees of the AFFIRM study for the
      NHLBI AFFIRM investigators.
AB  - The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM)
      Study is a randomized evaluation of treatment of atrial fibrillation by 1 of 2
      strategies: ventricular rate control and anticoagulation versus rhythm control
      and anticoagulation. The primary end point is total mortality, analyzed by
      intention-to-treat. Secondary end points are composite end points (total
      mortality, disabling intracranial bleed [subdural and/or subarachnoid
      hemorrhage], stroke [embolus, thrombosis, hemorrhage], disabling anoxic
      encephalopathy, cardiac arrest, major noncentral nervous system bleed), cost of
      therapy, and quality of life. AFFIRM will randomize therapy and follow 5,300
      patients for an average of 3.5 years (minimum 2 years) at 200 sites in the United
      States and Canada.

PMID- 9164887
TI  - Joseph Stephen Alpert, MD: a conversation with the editor. Interview by William
      Clifford Roberts.

PMID- 9164886
TI  - Usefulness of signal-averaged electrocardiography in evaluation of idiopathic
      dilated cardiomyopathy in families.
AB  - Family studies have confirmed that familial dilated cardiomyopathy is common and
      that a large proportion of relatives have mild left ventricular enlargement and
      therefore potentially early disease. Previous studies have shown that patients
      with idiopathic dilated cardiomyopathy have abnormalities of the signal-averaged
      electrocardiogram (ECG). We assessed the usefulness of analysis of the signal
      averaged ECG in the evaluation of familial dilated cardiomyopathy. Signal
      averaged electrocardiographic recordings were obtained from 58 patients with
      idiopathic dilated cardiomyopathy, from 161 of their relatives (35 of whom had
      left ventricular enlargement), and from 59 healthy subjects. Signal-averaged ECGs
      were analyzed using both time domain and spectral turbulence analysis techniques.
      The time domain and spectral turbulence analysis variables were markedly abnormal
      in patients with idiopathic dilated cardiomyopathy compared with relatives
      considered normal and healthy controls (p <0.05). Late potentials were more
      common in patients with idiopathic dilated cardiomyopathy (17%) and in relatives
      with left ventricular enlargement (20%) than in normal relatives (5%) or healthy
      controls (5%) (p = 0.003). Spectral turbulence analysis was abnormal in 24% of
      patients with idiopathic dilated cardiomyopathy, 14% of relatives with left
      ventricular enlargement, 6% of normal relatives, and 5% of healthy controls (p =
      0.0006). The sensitivity, specificity, and positive predictive accuracy for
      identification of relatives with left ventricular enlargement were 20%, 95%, and
      54% for time domain analysis and 14%, 94%, and 42% for spectral turbulence
      analysis. Similar positive predictive accuracy was achievable with spectral
      turbulence analysis and with time domain analysis. In conclusion, the signal
      averaged ECG is frequently abnormal in patients with idiopathic dilated
      cardiomyopathy and relatives with left ventricular enlargement.

PMID- 9164888
TI  - Literature and Medicine: the human experience.
AB  - The study of literature and medicine has developed into an independent discipline
      over the last 20 years. Literature and medicine are both humanistic arts,
      involving issues of morality, emotion, and philosophy.

PMID- 9164889
TI  - The pacemaker syndrome -- a matter of definition.
AB  - Pacemaker syndrome is an iatrogenic disease that is often underdiagnosed. We
      propose that pacemaker syndrome represents the clinical consequences of
      suboptimal atrioventricular (AV) synchrony or AV dyssynchrony, regardless of the
      pacing mode. Clinicians implanting and programming pacemakers should attempt to
      optimize AV synchrony to prevent the occurrence of pacemaker syndrome.

PMID- 9164890
TI  - Early deterioration after excimer laser-assisted coronary angioplasty.
AB  - Coronary lumen changes after excimer laser coronary angioplasty, after adjunct
      percutaneous transluminal coronary angioplasty, and at 24 hours after
      intervention were assessed using quantitative coronary angiography. Lesions
      treated with this combined technique showed significant early deterioration
      within 24 hours.

PMID- 9164891
TI  - Incidence and impact on outcome of streptokinase allergy in the GUSTO-I trial.
      Global Utilization of Streptokinase and t-PA in Occluded Coronary Arteries.
AB  - We evaluated allergic reactions in 20,201 patients randomized to the
      streptokinase arms of The Global Utilization of Streptokinase and t-PA (Tissue
      Plasminogen Activator) in Occluded Coronary Arteries (GUSTO-I) trial, and tested
      the hypothesis that patients with streptokinase allergy would exhibit higher
      mortality. After adjusting for baseline variables and time of death, we found
      comparable coronary patency, left ventricular function, mortality, and bleeding
      complications between patients with versus those without streptokinase allergy.

PMID- 9164892
TI  - Left ventricular size determined by electron beam computed tomography predicts
      significant coronary artery disease and events.
AB  - A novel method in the measurement of left ventricular (LV) area using noncontrast
      electron beam computed tomography (EBCT) was introduced and studied as a
      diagnostic and prognostic marker for coronary artery disease. Larger LV area
      measured by noncontrast EBCT was significantly associated with angiographic
      coronary disease and was a better predictor of coronary disease events than log
      calcium score.

PMID- 9164893
TI  - Radial versus femoral approach for diagnostic coronary angiography in stable
      angina pectoris.
AB  - We compared coronary angiography of the radial artery using 6Fr catheters in 116
      patients with that of the femoral artery in 100 case controls. We showed that
      transradial coronary angiography offers a useful alternative to the femoral route
      and can be performed without resorting to 5Fr catheters.

PMID- 9164894
TI  - Myocardial injury after electrical therapy for cardiac arrhythmias assessed by
      troponin-T release.
AB  - Episodes of ventricular fibrillation with subsequent intracardiac, and to a
      lesser extent, external defibrillation give rise to a statistically significant
      increase in S-troponin T, S-CK-MB(mass) and S-myoglobin indicative of a minor
      myocardial injury or dysfunction. In contrast, no such signs were observed after
      external direct-current conversion of atrial fibrillation using high energies, or
      after pace-terminated ventricular tachycardia.

PMID- 9164896
TI  - Efficacy of atorvastatin in primary hypercholesterolemia. Japan Cholesterol
      Lowering Atorvastatin Study (J-CLAS) Group.
AB  - A placebo-controlled, double-blind study on the efficacy of atorvastatin was
      conducted in several multicenters. Atorvastatin reduced total cholesterol, low
      density lipoprotein cholesterol, and apolipoprotein B substantially in a dose
      dependent manner without any serious adverse events.

PMID- 9164895
TI  - Absence of human herpesvirus 8 genomes in coronary atherosclerosis in
      immunocompetent patients.
AB  - Human herpevirus 8 (HHV8) has been localized to the endothelial and spindle cells
      of KS, suggesting a role for HHV8 in atherosclerosis. None of the 38 coronary
      atherectomy specimens contained HHV8 with both sensitive nested PCR assays,
      making it unlikely that persistent viral infection with HHV8 plays a role in
      coronary atherogenesis in the general population of the United States.

PMID- 9164897
TI  - Effect of sustained-release Verapamil on the morning systemic arterial pressure
      surge during daily activity in patients with systemic hypertension.
AB  - In a placebo-controlled study of 13 subjects with systemic hypertension,
      sustained-release verapamil reduced the morning surge in systolic pressure by
      10.2 mm Hg (p = 0.04), diastolic pressure by 11.1 mm Hg (p = 0.008), and heart
      rate by 3.3 beats/min (p = 0.17). Blunting of the morning hemodynamic surge may
      be a mechanism by which verapamil could reduce the risk of plaque disruption and
      acute coronary events in the morning.

PMID- 9164898
TI  - Disparity between diastolic mitral flow characteristics and left ventricular mass
      in essential hypertension.
AB  - Because left ventricular (LV) hypertrophy and aging have been associated with
      abnormal LV relaxation, this study evaluated the impact of LV mass on the filling
      patterns derived by Doppler in a large population aged > or =50 years. Results
      suggest that in essential hypertension the intrinsic myocardial composition is
      more important than cardiac hypertrophy in determining LV diastolic properties.
      This apparent discrepancy between LV mass and diastolic filling patterns
      highlights the difficulty in establishing the diagnosis of diastolic dysfunction
      in elderly hypertensives.

PMID- 9164899
TI  - Comparison of adaptations to a 12-month exercise program and late outcome in
      patients with healed myocardial infarction and ejection fraction <45% and >50%.
AB  - To characterize the differences in adaptations to endurance exercise training and
      prognosis between patients with depressed and normal left ventricular (LV)
      function, 20 patients with coronary artery disease were studied and followed for
      7 years. Patients with normal LV function had enhancement of LV systolic
      function, but the group with LV dysfunction did not exhibit cardiac adaptations
      and had more cardiac events than those with normal LV function.

PMID- 9164900
TI  - Isometric handgrip exercise increases endothelin-1 plasma levels in patients with
      chronic congestive heart failure.
AB  - This study demonstrated an immediate and short-lasting endothelin-1 release in
      the circulation of patients with severe chronic congestive heart failure during
      isometric handgrip exercise, but not in normal subjects. Our data suggest that
      endothelin-1 levels may increase transiently during daily physical activity, thus
      contributing to progressive deterioration of left ventricular function.

PMID- 9164902
TI  - Skeletal muscle atrophy and peak oxygen consumption in heart failure.
AB  - We measured skeletal muscle mass and peak oxygen consumption (VO2) in 13
      cachectic heart failure patients, 14 noncachectic patients, and in 52 healthy
      controls to examine skeletal muscle atrophy and its relation to low peak VO2 in
      heart failure patients. Our results show that skeletal muscle atrophy is
      associated with prior weight loss and is related to low peak VO2 in heart failure
      patients.

PMID- 9164901
TI  - Exercise-related ventilatory abnormalities and survival in congestive heart
      failure.
AB  - This retrospective study of 104 New York Heart Association class 1 to 4 heart
      failure patients undergoing exercise stress testing with gas exchange analysis
      demonstrated that the ventilatory equivalent for carbon dioxide at anaerobic
      threshold is useful in determining prognosis in patients with severe congestive
      heart failure, particularly when used in combination with peak exercise oxygen
      consumption. A ventilatory equivalent for carbon dioxide >50 and peak oxygen
      consumption < or =15.0 ml/kg/min defines a very high-risk patient group who
      should be prioritized for transplantation.

PMID- 9164903
TI  - Mitral and tricuspid valve aneurysms evaluated by transesophageal
      echocardiography.
AB  - This report describes the clinical and transesophageal echocardiographic findings
      in 2 patients with mitral and 2 with tricuspid valve aneurysms and reviews the 19
      published echo-diagnosed cases. One of our patients with a mitral valve aneurysm
      and 12 of those in the published reports had associated aortic valve
      endocarditis.

PMID- 9164904
TI  - Transgastric Doppler echocardiographic assessment of the severity of aortic
      stenosis using multiplane transesophageal echocardiography.
AB  - We investigated whether multiplane transesophageal Doppler echocardiography using
      transgastral views allows determination of pressure gadients and valve areas in
      patients with aortic stenosis. This technique was feasible in 35 of 39 patients
      (90%), with highly significant correlations with results obtained from
      transthoracic Doppler echocardiography and cardiac catheterization, thus offering
      an alternative approach for quantification of aortic stenosis.

PMID- 9164905
TI  - Long-term prognosis in patients with alcoholic cardiomyopathy and severe heart
      failure after total abstinence.
AB  - We prospectively evaluated the long-term prognosis of 14 patients with alcoholic
      cardiomyopathy and severe end-stage congestive heart failure after total
      abstinence. Improvement was very significant after 6 months of follow-up in most
      patients, and continued thereafter.

PMID- 9164906
TI  - Transcatheter closure of patent ductus arteriosus using coils.
AB  - Ninety-seven of 100 patients had a successful attempt at coil closure of the
      patent ductus arteriosus. For all 46 patients in whom a single coil and in 47
      patients in whom multiple coils were placed, there was immediate complete closure
      that persisted at a median follow-up period of 1.9 years.

PMID- 9164907
TI  - Cost-effectiveness of transaxillary muscle-sparing same-day operative closure of
      patent ductus arteriosus.
AB  - Transaxillary muscle-sparing patent ductus arteriosus closure performed as same
      day surgery is described in 10 patients. This approach provides a superb cosmetic
      result while obviating the need for thoracostomy tube placement.

PMID- 9164908
TI  - Coil occlusion versus conventional surgical closure of patent ductus arteriosus.
AB  - This retrospective cohort study evaluated the clinical outcome and cost
      effectiveness of 2 treatment strategies for children with an isolated restrictive
      patent ductus arteriosus. Results indicate a superior cost-effectiveness of
      transcatheter coil occlusion compared with conventional surgery for these
      patients.

PMID- 9164909
TI  - Aortic valve prolapse and aortic regurgitation associated with subpulmonic
      ventricular septal defect.
AB  - The natural development of aortic valve deformity was studied in 315 patients
      with subpulmonic ventricular septal defect. The patients with early development
      of aortic regurgitation had a pulmonary-to-systemic flow ratio of > 1.5, normal
      right ventricular pressure, and severe aortic regurgitation.

PMID- 9164910
TI  - Validity of electrocardiographic estimates of left ventricular hypertrophy and
      mass in African Americans (The Charleston Heart Study).
AB  - The Cornell voltage criteria and the Novacode computer model for estimating left
      ventricular mass were compared to echocardiographic left ventricular mass in
      African Americans from the Charleston Heart Study. The diagnostic accuracy of
      these electrocardiographic models compared with the echocardiogram is similar to
      the previous study in whites.

PMID- 9164911
TI  - Value of cardiac ultrafast computed tomography for detecting right atrial thrombi
      in chronic atrial fibrillation.
AB  - We evaluated the accuracy of cardiac ultrafast computed tomography in diagnosing
      atrial thrombi in 70 patients with chronic atrial fibrillation, and identified
      the predictors of atrial thrombi from among clinical, echocardiographic, and
      ultrafast computed tomographic features. Ultrafast computed tomography identified
      11 atrial thrombi in 9 patients: 4 patients had thrombi in the left atrium, 3 in
      the right, and 2 in both. Transthoracic echocardiography detected only 4 left
      atrial thrombi, and enlargement of the left or right atrium was associated with
      atrial thrombi (p <0.05).

PMID- 9164912
TI  - Prevalence of normal resting left ventricular function with normal rest
      electrocardiograms.
AB  - This study examined the prevalence of normal resting left ventricular function in
      2,275 patients referred for technetium-99m sestamibi stress imaging. The
      strongest predictor of normal left ventricular function was a normal
      electrocardiogram at rest.

PMID- 9164913
TI  - Comparison of pravastatin with crystalline nicotinic acid monotherapy in
      treatment of combined hyperlipidemia.
AB  - Pravastatin treatment of combined hyperlipidemia lowers low-density lipoprotein
      effectively; nicotinic acid lowers remnant cholesterol and raises high-density
      lipoprotein. A combination of these 2 drugs may be indicated for optimal
      treatment of lipoprotein abnormalities in combined hyperlipidemia.

PMID- 9164914
TI  - Neurohormonal response to head-up tilt and its role in vasovagal syncope.
AB  - In a controlled study, 26 patients with a history of recurrent syncope were found
      to have increased arginine vasopressin, corticotrophin, and atrial natriuretic
      factor levels after 5 minutes of 60 degrees head-up tilt, long before they became
      hypotensive. The exaggerated neurohormonal response in these patients may
      indicate a greater sensitivity to central hypovolemia which may predispose to
      vasovagal syncope, mediated by the vasodilatory effects of atrial natriuretic
      factor or the sensitization of mechanoreceptors by arginine vasopressin.

PMID- 9164915
TI  - What is a stent and where can you get one.
AB  - The development of the word stent as we use it today refers to a material to hold
      tissues in position or to make tissues patent. Dr. Charles Thomas Stent, a 19th
      century London dentist, created a compound for dental impressions that was used
      to hold skin grafts in place by later plastic surgeons, presaging its present
      usage.

PMID- 9164916
TI  - Anomalous origin of the left main coronary artery from the pulmonary trunk
      masquerading as peripartum cardiomyopathy.
AB  - We present a 16-year-old girl who developed congestive heart failure during and
      after delivery of her first child, and who was diagnosed as having peripartum
      cardiomyopathy. Cardiac catheterization with coronary arteriography confirmed the
      correct diagnosis of anomalous origin of the left main coronary artery from the
      pulmonary trunk.

PMID- 9164917
TI  - A newly recognized pathway for the negative regulation of mast cell-dependent
      hypersensitivity and inflammation mediated by an endogenous cell surface receptor
      of the gp49 family.
AB  - Mast cells are constitutively present at the portals between self and nonself,
      and contain a large and diverse complement of proinflammatory mediators. These
      characteristics suggest that the activation of mast cells must be carefully
      regulated in vivo. Regulation of pathologic and physiologic mast cell activation
      has been traditionally associated simply with the presence or absence of an
      activating signal. We examine here evidence supporting a new paradigm: mast cell
      homeostasis may result from inhibition of activation mediated by receptors on the
      surface of mast cells, typified by a member of the gp49 family.

PMID- 9164918
TI  - Regulation of the RAG-1 promoter by the NF-Y transcription factor.
AB  - We have cloned the RAG-1 promoter region and have determined that almost all
      detectable promoter activity resides within a 208-bp fragment. Sequence analysis
      of this promoter region has identified potential recognition motifs for a number
      of lymphocyte-restricted and ubiquitous transcription factors. Subsequent assays
      have revealed that the NF-Y transcription factor interacts with a CCAAT site
      within the RAG-1 promoter and appears to play an important role in the positive
      transcriptional regulation of this gene.

PMID- 9164919
TI  - Abnormal T lymphocyte development induced by targeted overexpression of IkappaB
      alpha.
AB  - A role in thymic maturation for factors of the NF-kappaB family has long been
      suspected, but not yet proven. Transgenic mice with a lymphocyte-specific defect
      in NF-kappaB activation were produced by targeted expression of human IkappaB
      alpha. The thymic cellularity of these mice was significantly decreased. The
      proportion of mature, TCRhigh thymocytes of the alphabeta lineage was reduced,
      and the remaining TCRhigh population contained an unusually high proportion of
      double-positive cells. This defect in maturation resulted in a transgene dose
      dependent reduction in peripheral T lymphocytes, with the CD8 lineage being more
      severely affected. These data provide direct evidence for the involvement of NF
      kappaB/Rel family proteins in late stages of T lymphocyte development, coincident
      with positive and negative selection.

PMID- 9164920
TI  - Inhibition of graft-versus-host disease. Use of a T cell-controlled suicide gene.
AB  - Graft-vs-host disease (GVHD) after allogeneic bone marrow transplantation is
      associated with significant morbidity and mortality. T cell depletion of the
      marrow graft, which is currently used to prevent GVHD, has been shown to result
      in increased graft failure and leukemia relapse. To explore the feasibility of
      controlling GVHD, transgenic mice with the herpes simplex virus thymidine kinase
      suicide gene linked to the IL-2 promoter were used as a source of T cells to
      induce GVHD, which would be modulated with ganciclovir. Injection of herpes
      simplex virus thymidine kinase transgenic B10.A(5R) spleen cells into lethally
      irradiated DBA/2 mice resulted in severe acute GVHD. Treatment of the recipient
      mice with ganciclovir significantly inhibited GVHD-mediated weight loss and
      mortality and reduced the severity of inflammation in the target organs of GVHD.

PMID- 9164921
TI  - Human killer cell activatory receptors for MHC class I molecules are included in
      a multimeric complex expressed by natural killer cells.
AB  - Engagement of killer cell inhibitory receptors (KIRs) with their MHC class I
      ligands inhibits T and NK lymphocyte activation. In humans, killer cell
      activatory receptors (KARs) are highly homologous to KIRs, interact with an
      identical set of MHC class I molecules, and are encoded by individual genes
      belonging to the Ig-like superfamily. In contrast to KIRs, engagement of KARs
      leads to T and NK cell activation. We identified a set of disulfide-linked dimers
      selectively associated with KARs. KAR-associated polypeptides (KARAPs) are
      phosphorylated on tyrosine and serine residues. Reconstitution of KAR cell
      surface expression in the absence of KARAPs correlates with the failure of KAR to
      transduce any detectable activation signals. These results indicate that KARs are
      included in a multimeric complex with phosphorylated KARAPs and define a novel
      set of polypeptides that are likely to be involved in the control of lymphocyte
      activation upon MHC class I recognition.

PMID- 9164922
TI  - Microbial products induce autoimmune disease by an IL-12-dependent pathway.
AB  - The development and exacerbation of autoimmune diseases are associated with
      antecedent infectious illness. Microbial products such as LPS, bacterial DNA, or
      oligonucleotides containing an unmethylated cytosine-guanine dinucleotide have
      cytokine modulating properties. These products converted quiescent myelin basic
      protein-specific T cells into effector cells capable of transferring experimental
      allergic encephalomyelitis. The disease-promoting properties of the microbial
      products were solely dependent on their capacity to induce the production of IL
      12.

PMID- 9164923
TI  - CTLA4Ig prevents lymphoproliferation and fatal multiorgan tissue destruction in
      CTLA-4-deficient mice.
AB  - Mice lacking CTLA-4 develop a fatal spontaneous lymphoproliferative disease with
      massive lymphocytic infiltrates and tissue destruction in many organs. CTLA-4
      deficient (-/-) splenocytes and lymph node cells proliferate without added
      stimuli in vitro. We report here that CTLA4Ig treatment of CTLA-4 -/- mice
      prevents lymphoproliferation and fatal multiorgan tissue damage in vivo and
      proliferation of CTLA-4 -/- splenocytes and lymph node cells in vitro. Therefore,
      stimulation via CD28-B7 interactions appears necessary for CTLA-4 -/- T cell
      proliferation and the production of lymphoproliferative disease in vivo. When
      CTLA4Ig treatment is terminated, CTLA-4 -/- T cells become activated and
      lymphoproliferative disease develops. The lack of long term protective effects of
      CTLA4Ig treatment suggests that CTLA-4 is needed for the induction and or
      maintenance of tolerance.

PMID- 9164924
TI  - Effects of extracellular ATP and adenosine on different thymocyte subsets:
      possible role of ATP-gated channels and G protein-coupled purinergic receptor.
AB  - To explore the possible role of purinergic receptors in thymocyte development and
      in pathogenesis of adenosine deaminase SCID, we studied effects of extracellular
      adenosine triphosphate (ATP(ext)) and adenosine on TCR- and steroid hormone
      triggered processes in mouse thymocytes. Reverse transcriptase-PCR analysis
      confirms the mRNA expression of several types of purinergic receptors, while the
      functioning of ATP receptors in thymocytes is reflected by ATP(ext)-induced
      intracellular calcium increases and by thymocyte subset-specific sensitivity to
      the effects of ATP(ext) and adenosine. Only ATP(ext), but not the ATP
      catabolites, adenosine, dexamethasone, or TCR cross-linking, was efficient in
      triggering rapid protein synthesis independent lysis of CD4+8- thymocytes and
      peripheral CD4+ T cells. In contrast, extracellular adenosine specifically
      induced the apoptosis of CD4+8+ thymocytes. ATP(ext) also induced a slower
      process of DNA fragmentation and protein synthesis-dependent apoptosis in all
      thymocyte subsets. ATP(ext) had an additive effect with TCR cross-linking in the
      induction of thymocyte death, but, unexpectedly, the effects of ATP(ext) at high
      concentration were antagonistic to steroid-induced apoptosis. Described here, the
      properties of ATP(ext) and adenosine are consistent with their involvement in the
      regulation of T cell development due to differential expression and signaling
      through purinergic receptors in different thymocyte subsets. The possible role of
      purinergic receptor signaling in T cell differentiation and adenosine deaminase
      SCID is discussed.

PMID- 9164925
TI  - Correlation of tolerogenicity of a viral antigen with its immunogenicity.
AB  - Induction of B cell tolerance or activation was analyzed with vesicular
      stomatitis virus (VSV) glycoprotein (G) expressed as a neo-self Ag. A membrane
      form of VSV-G expressed in all tissues, including the bone marrow, induced
      unresponsiveness at both the Th and B cell level, whereas a soluble form of VSV-G
      expressed peripherally in liver and kidney did not tolerize B cells and only
      reversibly anergized Th cells. Interestingly, a similar correlation was found for
      activation of mature lymphocytes. When mature normal spleen cells were
      transferred into the two transgenic mouse lines, the membrane form of VSV-G was
      strongly immunogenic for both Th and B cells, and high VSV-G-specific IgG Ab
      titers were induced in these transgenic mice. In contrast, spleen cells
      transferred into mice expressing the soluble form of VSV-G were not activated,
      and no VSV-G specific Abs were induced. These results indicate that highly
      immunogenic Ags are strongly tolerogenic for both immature B and T cells.

PMID- 9164926
TI  - NK1.1+ CD4+ T cells lose NK1.1 expression upon in vitro activation.
AB  - NK1.1+ CD4+ T cells produce IL-4 promptly in vivo upon injection of anti-CD3 and
      may play a role in initiating Th2 cell-mediated immunity. To characterize their
      in vitro activation properties, NK1.1+ CD4+ T cells were obtained in high purity
      from spleens of normal C57BL/6 mice, where they represent 2 to 5% of CD4+ T
      cells, or from MHC-class II I-Ab gene knockout mice, where they constitute 42% of
      CD4+ T cells. Activation of NK1.1+ CD4+ T cells from either source with plate
      bound anti-CD3 resulted in loss of expression of NK1.1 as determined both by flow
      cytometric analysis and by reverse transcriptase-PCR analysis. A portion of these
      cells also lost CD4 expression. Both the CD4+ and CD4- activated cells retained
      the over-representation of V beta8 and V alpha14 chains and expressed the
      intermediate levels of the TCR-CD3 complex that is characteristic of resting
      NK1.1+ CD4+ T cells. The anti-NK1.1 mAb used for cell sorting was not the cause
      of NK1.1 or CD4 disappearance, since the sorted cells remain both NK1.1+ and CD4+
      when cultured in the absence of anti-CD3 or in the presence of anti-CD3 and
      cyclosporin A. Furthermore, NK1.1+ CD4+ T cells that were not treated with anti
      NK1.1 Ab also lost NK1.1 expression after activation. Populations of activated
      CD4+ and CD4- cells (derived from NK1.1+ CD4+ T cells) produced both IL-4 and IFN
      gamma upon restimulation with plate-bound anti-CD3.

PMID- 9164927
TI  - Blockade of the voltage-gated potassium channel Kv1.3 inhibits immune responses
      in vivo.
AB  - The voltage activated K+ channel (Kv1.3) has recently been identified as the
      molecule that sets the resting membrane potential of peripheral human T lymphoid
      cells. In vitro studies indicate that blockage of Kv1.3 inhibits T cell
      activation, suggesting that Kv1.3 may be a target for immunosuppression. However,
      despite the in vitro evidence, there has been no in vivo demonstration that
      blockade of Kv1.3 will attenuate an immune response. The difficulty is due to
      species differences, as the channel does not set the membrane potential in rodent
      peripheral T cells. In this study, we show that the channel is present on
      peripheral T cells of miniswine. Using the peptidyl Kv1.3 inhibitor, margatoxin,
      we demonstrate that Kv1.3 also regulates the resting membrane potential, and that
      blockade of Kv1.3 inhibits, in vivo, both a delayed-type hypersensitivity
      reaction and an Ab response to an allogeneic challenge. In addition, prolonged
      Kv1.3 blockade causes reduced thymic cellularity and inhibits the thymic
      development of T cell subsets. These results provide in vivo evidence that Kv1.3
      is a novel target for immunomodulation.

PMID- 9164928
TI  - Dissociation of apoptosis and activation of IL-1beta-converting enzyme/Ced-3
      proteases by ALG-2 and the truncated Alzheimer's gene ALG-3.
AB  - Recent attention has been focused on the members of the IL-1beta-converting
      enzyme (ICE)/Ced-3 family of cysteine protease as the key components of
      programmed cell death. However, the molecular events that lead to protease
      activation and link it to the final apoptotic processes remain poorly
      characterized. We have shown recently that ALG-2 is a Ca2+-binding protein
      required for apoptosis. ALG-2 depletion protects the mouse T cell hybridoma 3DO
      from programmed cell death induced by several stimuli, such as synthetic
      glucocorticoids, TCR, and Fas triggering. In this work, we show that in the ALG-2
      depleted clones the ICE/Ced-3 proteases are normally activated upon TCR, Fas, and
      dexamethasone stimulation, as determined by cleavage of the endogenous substrate
      poly(ADP-ribose) polymerase and of a fluorogenic substrate. ALG-3, a truncated
      form of the familial Alzheimer's disease gene PS2, confers resistance to TCR- and
      Fas-induced apoptosis. Of interest, it also reduces protease activity and
      inhibits poly(ADP-ribose) polymerase cleavage upon Fas triggering. Our results
      suggest that, during apoptosis, ALG-2 functions downstream of, and that ALG-3
      interferes with the sequential activation of members of the ICE family proteases.

PMID- 9164929
TI  - Apoptosis during B lymphopoiesis in mouse bone marrow.
AB  - To evaluate the magnitude of cell death and the critical stages at which it
      occurs during B lymphopoiesis in mouse bone marrow (BM), we have examined the
      kinetics of apoptosis at defined stages of B cell differentiation. FACS-sorted
      B220+ BM cells exhibited a low incidence of morphologically apoptotic cells by
      electron microscopy. In freshly prepared BM suspensions, the incidence of
      hypodiploid cells detected by multiparameter flow cytometry was greater among
      large dividing B220+ surface IgM- (sIgM-) precursor B cells and sIgM(low)
      immature B lymphocytes than among terminal deoxynucleotidyl transferase+ (TdT+)
      pro-B cells, small nondividing B220+ sIgM- precursors, and surface IgD+ mature B
      lymphocytes. During short-term culture, apoptotic cells, identified by both DNA
      content and in situ DNA strand break labeling, increased linearly with time
      without macrophage ingestion, providing an assay for the rate of entry into
      apoptosis. B220+ B lineage cells accumulated in apoptosis more rapidly than cells
      of other lineages. The apoptotic rate was greater among B220+ sIgM- precursor
      cells than sIgM+ B cells, and was highest among B220+ mu- pro-B cells. Coculture
      with stromal cells reduced the apoptotic rate of B220+ sIgM- precursors to a
      greater extent than that of sIgM+ B lymphocytes. The results lead to estimates of
      the actual number of B lineage cells undergoing apoptosis per unit time in
      successive differentiation compartments. The findings indicate that, although
      influenced by local microenvironmental factors, apoptotic cell death occurs most
      markedly at two developmental stages associated with Ig heavy chain gene
      rearrangement and Ag receptor expression, respectively.

PMID- 9164930
TI  - Rapid nuclear translocation and increased activity of cyclin-dependent kinase 6
      after T cell activation.
AB  - To elucidate the roles of cyclin-dependent kinase 6 (cdk6) in T cells, we
      examined its intracellular localization, kinase activity, and associated proteins
      in the Jurkat T lymphoblastoid cell line. Jurkat cells had a high level of cdk6,
      which was associated with cyclin D3, but not cyclin D2, the member of the cyclin
      D family. When stimulated by a combination of PHA and anti-CD28 mAb, cdk6
      activity was up-regulated, as measured by an in vitro kinase assay using
      recombinant, truncated retinoblastoma tumor suppressor gene protein (Rb protein)
      as substrate. Activation was most prominent when cells were stimulated with the
      combination of PHA and anti-CD28, although significant increases were detected
      after stimulation with PHA alone. The combination also resulted in maximal
      activation of c-Jun kinase and IL-2 production. Costimulation resulted in a rapid
      translocation of cdk6 to the nucleus, as demonstrated by both confocal
      immunofluorescence microscopy and biochemical fractionation techniques. Cdk6
      activation and nuclear translocation were also observed after stimulation of
      Jurkat cells using the anti-CD28 Ab in combination with a mAb to CD3 (OKT3).
      Furthermore, nuclear translocation was observed in normal human T lymphocytes
      isolated from peripheral blood and stimulated in vitro with PHA. Two potential
      endogenous cdk6 substrates (with apparent molecular masses of 75-80 and 55-60
      kDa), which were immunoprecipitated with cdk6 and phosphorylated in the in vitro
      kinase assay, were also identified. These data demonstrate the rapid activation
      and intracellular translocation of cdk6, implicating this kinase in early signal
      transduction events in T cells.

PMID- 9164931
TI  - Somatic mutation leads to efficient affinity maturation when centrocytes recycle
      back to centroblasts.
AB  - Although most mutations are deleterious, an interplay between somatic mutation
      and selection within germinal centers (GC) results in rapid generation of high
      affinity memory B cells. How high affinity B cells with large numbers of
      mutations are generated and preserved within GC containing at their peak only a
      few thousand cells has been puzzling. We have developed a model of somatic
      mutation and B cell expansion within a GC that resolves this puzzle. We show that
      the frequent recycling of Ag-selected centrocytes back into centroblasts can lead
      to efficient affinity maturation. Memory cells are generated in large numbers
      even when most of the selected centrocytes recycle back into centroblasts. Our
      model suggests that a germinal center reaction in which the output of cells is
      low up to the point of GC dissociation, followed by the release of centrocytes
      into the periphery, is advantageous for generating high affinity memory.

PMID- 9164932
TI  - Diurnal rhythmicity of human cytokine production: a dynamic disequilibrium in T
      helper cell type 1/T helper cell type 2 balance?
AB  - Diurnal rhythmicity is a characteristic of neuroendocrine pathways but is less
      understood in relation to immune function. We asked whether cellular (type 1) or
      humoral (type 2) immune responses or type 1/type 2 balance exhibit diurnal
      rhythmicity in healthy humans, and, if so, whether this is related to plasma
      levels of cortisol or melatonin, two hormones with immunomodulatory actions. LPS-
      or tetanus-stimulated human whole blood IFN-gamma and IL-10 production, and the
      IFN-gamma/IL10 ratio exhibited significant diurnal rhythmicity. The IFN-gamma/IL
      10 ratio peaked during the early morning and correlated negatively with plasma
      cortisol and positively with plasma melatonin. IFN-gamma and, to a lesser extent,
      IL-10 production was sensitive to inhibition by exogenous cortisone; the IFN
      gamma/IL-10 ratio decreased by >70% after the administration of oral cortisone
      acetate (25 mg). Our findings support the concept that plasma cortisol and
      possibly melatonin regulate diurnal variation in the IFN-gamma/IL-10 ratio. As
      IFN-gamma and IL-10 have opposing effects on cellular immunity, changes in their
      balance would be anticipated to impose diurnal rhythmicity on cellular immunity.
      This implies that the nature of an immune response, e.g., to vaccination, may be
      modified by the time of day of Ag presentation and could be therapeutically
      manipulated by the administration of cortisol or melatonin.

PMID- 9164934
TI  - Indirect suppression of IL-7-responsive B cell precursors by vasoactive
      intestinal peptide.
AB  - Bone marrow is supplied with nerves and neuropeptides that influence a variety of
      cellular responses. This study represents an initial evaluation of vasoactive
      intestinal peptide (VIP) as a possible regulator of B lineage lymphocyte
      formation. As little as 10(-10) M concentrations of VIP inhibited the IL-7-driven
      clonal proliferation of pre-B cells in semisolid agar cultures. The response was
      blocked by a VIP antagonist and augmented by the ectoenzyme inhibitor,
      phosphoramidon. Suspensions of highly enriched B lineage precursors were
      unaffected by VIP unless they were cocultured with macrophage-like cells and
      conditioned medium from VIP-treated macrophages contained inhibitory activity.
      Neutralizing Abs were used to determine that IFN-alpha is at least one substance
      that is elicited by exposure of macrophages to VIP. These findings suggest that a
      neuropeptide can potentially modulate lymphopoiesis through a regulatory circuit
      that involves macrophages and IFN-alpha. They also raise the possibility that VIP
      can participate in antiviral defense.

PMID- 9164933
TI  - Thrombopoietin directly and potently stimulates multilineage growth and
      progenitor cell expansion from primitive (CD34+ CD38-) human bone marrow
      progenitor cells: distinct and key interactions with the ligands for c-kit and
      flt3, and inhibitory effects of TGF-beta and TNF-alpha.
AB  - Thrombopoietin (Tpo) is a primary regulator of megakaryocyte and platelet
      production. However, studies in c-mpl-deficient mice suggest that Tpo might also
      play an important role in early hemopoiesis. Here, the direct ability of Tpo to
      stimulate stroma-independent growth, multilineage differentiation, and progenitor
      cell expansion from single primitive CD34+ CD38- human bone marrow cells was
      investigated. Tpo alone stimulated limited clonal growth, but synergized with c
      kit ligand (KL), flt3 ligand (FL), or IL-3 to potently enhance clonogenic growth.
      Whereas KL and FL in combination stimulated the clonal growth of only 3% of CD34+
      CD38- cells, 40% of CD34+ CD38- cells were recruited by KL+FL+Tpo, demonstrating
      that Tpo promotes the growth of a high fraction of CD34+ CD38- progenitor cells.
      Additional cytokines (IL-3, IL-6, and erythropoietin (Epo)) did not significantly
      enhance clonal growth above that observed in response to KL+FL+Tpo. In contrast,
      Tpo enhanced clonogenic growth in response to KL+FL+IL-3+IL-6+Epo by as much as
      80%, implicating a key role for this cytokine in early hemopoiesis. Importantly,
      we also demonstrate that the majority of Tpo-recruited CD34+ CD38- progenitor
      cells have a multilineage differentiation potential, and that Tpo promotes
      prolonged expansion of multipotent progenitors. Specifically, whereas progenitor
      cells were reduced in cultures containing only KL+FL, addition of Tpo resulted in
      40-fold expansion of multipotent progenitors following a 14-day incubation.
      Finally, we identified inhibitors of Tpo-induced progenitor cell growth, in that
      TGF-beta as well as TNF-alpha almost completely abrogated the growth of CD34+
      CD38- progenitor cells in response to Tpo alone as well as KL+FL+Tpo.

PMID- 9164935
TI  - TNF receptor p55 controls early acute graft-versus-host disease.
AB  - Allogeneic bone marrow transplantation is frequently associated with graft-vs
      host disease (GVHD). To understand the effector mechanisms of GVHD, we
      investigated the role of the TNF receptor p55 (TNFRp55), which is known to be
      important in inflammation and cytotoxicity. After the transplantation of
      allogeneic bone marrow and spleen cells to lethally irradiated mice, all wild
      type recipients developed early lethal GVHD within 1 wk, whereas TNFRp55
      deficient recipients had much reduced GVHD and survived for at least 3 wk. No
      defect in alloantigen presentation was found, since T cell proliferation and
      cytotoxicity were similar to allogeneic wild-type and TNFRp55-deficient
      stimulator and target cells. Also, TNF alpha release did not differ significantly
      between the two types of recipients. Therefore, early acute GVHD in wild-type
      mice was primarily due to TNFRp55-mediated tissue damage. Interestingly, lethal
      GVHD was not entirely dependent upon the TNFRp55. In experimental conditions
      using sublethal irradiation and high donor spleen cell numbers, TNFRp55-deficient
      recipient mice developed lethal GVHD with similar kinetics and frequency as the
      control mice. These data suggest that the effector mechanisms leading to organ
      damage in murine acute GVHD can be dissected in a cytokine pathway through the
      TNFRp55, as demonstrated here, and in a cellular pathway through direct
      interaction of cytotoxic lymphocytes with target tissues involving perforin and
      Fas/Fas ligand, as reported previously.

PMID- 9164936
TI  - L-selectin is involved in lymphocyte migration to sites of inflammation in the
      skin: delayed rejection of allografts in L-selectin-deficient mice.
AB  - Adhesion of leukocytes to vascular endothelium is crucial for leukocyte migration
      into tissues. The contributions of L-selectin, P-selectin, and ICAM-1 to
      interactions between lymphocytes and endothelium was examined using allogeneic
      skin graft rejection as a model of cutaneous inflammation. L-selectin-deficient
      (L-selectin(-/-)) mice rejected both primary and secondary allogeneic (BALB/c)
      skin grafts significantly more slowly than L-selectin(+/+) littermates.
      Furthermore, skin graft rejection remained significantly delayed in L-selectin(-/
      ) mice, despite placement of grafts 7 days after i.p. immunization with
      allogeneic cells, when CTL responses in L-selectin(-/-) mice and L-selectin(+/+)
      littermates were confirmed to be equivalent. Indeed, specific CTL responses to
      BALB/c splenocytes were normal or elevated in L-selectin(-/-) mice following
      either skin grafts or immunization. However, the number of T lymphocytes within
      allogeneic grafts was lower in L-selectin(-/-) mice as compared with L
      selectin(+/+) littermates. Therefore, delayed rejection of skin grafts by L
      selectin(-/-) mice reflects impaired migration of effector cells into the graft
      rather than delayed or impaired generation of a CTL response. In contrast to L
      selectin(-/-) mice, P-selectin-deficient and ICAM-1-deficient mice rejected
      allogeneic skin grafts normally. These findings delineate an important role for L
      selectin in lymphocyte recruitment to cutaneous sites of inflammation.

PMID- 9164937
TI  - A selective inhibitor of dipeptidyl peptidase I impairs generation of CD8+ T cell
      cytotoxic effector function.
AB  - CTL express high levels of dipeptidyl peptidase I (DPPI), a granule thiol
      protease able to convert the zymogen precursors of granzymes A and B into active
      proteases. In the present studies, the effects of specific inhibition of DPPI on
      generation of CTL effector functions were examined. When T cell DPPI activity was
      inhibited by >95% throughout 5-day MLC, a significant reduction in the generation
      of CD8+ T cell BLT esterase activity (<30% of control) and cytolytic activity
      (<10% of control) was observed. DPPI inhibition during the second to fourth days
      of 5-day MLC also was associated with reduced proliferation of CD8+ T cells, but
      had no effect on CD4+ T cell proliferation or IL-2 production by either
      population. CTL generated in the continuous presence of DPPI inhibition also
      exhibited impaired lysis of anuclear erythrocyte targets and diminished killing
      of nucleated targets by perforin-independent pathways. In contrast, inhibition of
      DPPI during only the last 24 h of 5-day MLC was associated only with reduced
      generation of BLT esterase activity and reduced lysis of nucleated targets by
      perforin-dependent pathways. Repeated or delayed inhibition of DPPI in MLC
      containing granzyme B-deficient responder cells also impaired generation of
      cytotoxic activity. These results indicate that DPPI or other DPPI-like protease
      activities not only are required for the activation of granzymes, but also play a
      role in the expansion and differentiation of full CD8+ T cell cytolytic activity.

PMID- 9164938
TI  - Multifocal defects in immune responses in RelB-deficient mice.
AB  - Mice with a targeted disruption of the Rel/nuclear factor-kappaB family member
      RelB develop a complex inflammatory phenotype, myeloid hyperplasia, and
      splenomegaly due to extramedullary hemopoiesis. In this work, we report that RelB
      deficient mice, in addition to the pathologic changes, were highly susceptible to
      infection by the facultative intracellular bacterium Listeria monocytogenes. RelB
      binds transcriptionally active kappaB motifs in the TNF-alpha promoter in normal
      cells, and in vitro studies with macrophages isolated from RelB-deficient animals
      revealed impaired production of TNF-alpha in response to LPS and IFN-gamma. RelB
      deficient mice also were unable to mount a protective immune response against
      lymphocytic choriomeningitis virus. These results indicate a defective T cell
      macrophage interaction and cytotoxic T cell response, respectively, in mice
      lacking RelB. Analysis of resting and specific Ab production demonstrated that
      while RelB is not required for the secretion of Ig isotypes that result from
      heavy chain class switching, it is necessary for normal production of Ag-specific
      IgG in response to T cell-dependent and -independent stimuli. Thus, RelB is not
      only essential for a normal hemopoietic system in the unchallenged animal, but
      also involved in various specific and nonspecific immune responses.

PMID- 9164939
TI  - Structurally similar TCRs differ in their efficiency of positive selection.
AB  - Studies of TCR transgenic mice have demonstrated that in these systems positive
      selection is not an efficient process. The capacity of the thymus to produce
      mature T cells is limited, even when all immature thymocytes express appropriate
      Ag receptors. Analysis of TCR transgenic mice expressing reduced levels of MHC
      molecules have shown that MHC surface density can be a limiting factor during
      development. Whether peptide availability in the thymus also limits the
      efficiency of positive selection remains controversial. Here, we examine the
      efficiency of positive selection in three similar lines of TCR transgenic mice,
      all of which express V alpha11/beta3+ TCRs specific for cytochrome c peptides
      bound to I-Ek. We demonstrate that thymocytes expressing these similar TCRs
      mature with very different efficiencies in H-2k mice. Furthermore, efficient
      positive selection of thymocytes expressing these three TCRs varies in its
      dependence on MHC density. These data suggest that similar TCRs can differ in
      their degree of specificity for peptide/MHC complexes during positive selection;
      some TCRs may require specific complexes for selection while other TCRs are more
      promiscuous in their thymic interactions. Alternatively, these three TCRs may
      differ in their affinities for positively selecting ligands.

PMID- 9164940
TI  - Gene transfer directly demonstrates a role for TCR V alpha elements in
      superantigen recognition.
AB  - Recent structure-function studies of ours and others indicating that regions of
      the TCR other than V beta are involved in the TCR-superantigen (SAg)-MHC class II
      trimolecular interaction were correlative; thus, while the conclusions were
      persuasive, they were not unequivocal. The transfection experiments described in
      this report show that 1) responsiveness to staphylococcal enterotoxin B in V
      beta6 T cells was transferred by a V alpha4- but not by V alpha8- and V alpha10
      containing alpha-chain cDNA constructs, 2) responsiveness was not transferred by
      a chimeric alpha-chain construct containing the N and J regions from a responsive
      T hybrid clone and the V alpha10 V alpha region from a nonresponsive clone, and
      3) responsiveness was transferred by a chimeric alpha-chain construct in which
      most of the V alpha region (from the N terminus to the C-terminal end of the
      complementarity-determining region 2) was derived from the V alpha4 alpha-chain
      of a responsive T hybrid and the rest (framework 3, N, and J) from the V alpha8
      alpha-chain of a nonresponsive T hybrid. Thus, these data provide the first
      direct evidence for a specific SAg response facilitating activity in a defined V
      alpha segment and map this activity N-terminal of framework region 3.
      Furthermore, the diversity in the alpha- and beta-chain junctional regions of a
      panel of staphylococcal enterotoxin B-responsive V beta6 T hybrid clones excludes
      a stringent corequirement for a particular junctional region for the V alpha4
      segment to mediate its facilitating activity. Finally, a model postulating a
      universal role for V alpha elements in TCR recognition of SAg is presented.

PMID- 9164941
TI  - Conserved and variable residues within the Bw4 motif of HLA-B make separable
      contributions to recognition by the NKB1 killer cell-inhibitory receptor.
AB  - Allotypes from four divergent HLA-B families (B8, B15, B16, and B27) were
      compared for their inhibition of cytolysis by NK cells expressing the NKB1
      receptor. Allotypes differing solely at the Bw4/Bw6 region were examined as were
      a more divergent subset of B15 allotypes. The capacity to interact with NKB1
      correlated precisely with possession of a Bw4 sequence motif at residues 77-83,
      whereas no correlation was made with the peptide-binding specificities of two Bw4
      and four Bw6 allotypes of the B15 family. HLA-B allotypes having four different
      Bw4 motifs were examined and all interact with NKB1. In contrast, HLA-A
      allotypes, which have a Bw4 motif identical with one of those present in HLA-B,
      do not. Mutation at leucine 82 and arginine 83, the residues common to Bw4
      motifs, shows they contribute to NKB1 interaction but are not essential. Three
      types of polymorphism are implicated in formation of the ligand recognized by
      NKB1: ones shared by Bw4 motifs; ones distinguishing Bw4 motifs; and ones outside
      the Bw4/Bw6 region that distinguish HLA-B from HLA-A.

PMID- 9164942
TI  - Natural inactivation of a common HLA allele (A*2402) has occurred on at least
      three separate occasions.
AB  - HLA-A*2402 is common and widely distributed in human populations. Several
      individuals were identified who type genotypically for A*2402, but are
      serologically null for the HLA-A24 Ag. Sequencing and transfection of genomic DNA
      fragments containing null and wild-type A*2402 alleles, and the related A*2301
      allele, revealed three different null alleles (A*2409N, A*2411N, and
      A*2402(low)), each of which differs from A*2402 by a single nucleotide change
      within the 6.7-kb sequence. The A*2301 and A*2402 sequences differ by no
      substitutions additional to those previously determined for the 1.1-kb cDNA. In
      exon 4, A*2409N has an in-frame stop codon, while A*2411N has a nucleotide
      insertion that alters the reading frame, causing premature termination.
      A*2402(low) has a nucleotide substitution near the splice acceptor site for
      intron 2 that impairs the production of correctly spliced mRNA. For A*2409N and
      A*2411N, mRNA is undetectable by Northern analysis, whereas A*2402(low) produces
      a low level of mRNA and a concomitant amount of normal A*2402 protein at the cell
      surface. The protein expressed from the A*2402(low) allele is sufficient to
      stimulate an alloreactive T cell response. On a background of unexpected sequence
      homogeneity, the single nucleotide changes in the A*2409N, A*2411, and
      A*2402(low) alleles have dramatic effects upon gene expression and are of likely
      importance for HLA matching in clinical transplantation. Segregation of at least
      three independently inactivated A*2402 alleles in human populations raises the
      possibility that loss of A*2402 may be the result of natural selection.

PMID- 9164943
TI  - Allelic variation in the mouse Tap-1 and Tap-2 transporter genes.
AB  - The TAP1 and TAP2 proteins form a heterodimer that transports short peptides from
      the cytosol into the endoplasmic reticulum lumen. Extensive allelic polymorphism
      of the rat TAP transporter has been shown to affect the repertoire of peptides
      presented by MHC class I molecules. Structural polymorphism in the human TAP
      genes is much more limited and has not been observed to have functional
      consequences. We have examined the polymorphism in mouse TAP1 and TAP2 in inbred
      mice. While the number of polymorphic positions in these molecules is more
      similar to that in human than to that in the rat, all strains examined have a
      structurally unique TAP transporter, suggesting the possibility of functional
      polymorphism. Furthermore, allelic variations in the mouse transporter are
      predominantly located in or adjacent to membrane-spanning domains, although no
      significant bias in the ratio of nonsynonymous to synonymous substitutions is
      observed. We also report that mouse TAP1 begins 172 amino acids upstream of the
      previously published start site and report the genomic organization of mouse Tap
      1 and Tap-2.

PMID- 9164944
TI  - Cloning and characterization of the human granulocyte chemotactic protein-2 gene.
AB  - We recently described a novel murine CXC chemokine, designated lipopolysaccharide
      induced CXC chemokine (LIX). In an ongoing search for new human chemokines
      related to LIX, we cloned the gene for human granulocyte chemotactic protein-2
      (GCP-2) as well as previously described CXC chemokine genes, including epithelial
      cell-derived neutrophil-activating peptide-78 (ENA-78). Both coding and noncoding
      portions of the GCP-2 gene have very high nucleotide similarity to ENA-78, except
      for the occurrence of a long interspersed DNA-1 sequence 5' of the GCP-2 gene.
      The GCP-2 gene encodes a propeptide of 114 amino acid residues. The predicted 77
      residue mature peptide is identical with the GCP-2 protein previously isolated
      from MG-63 osteosarcoma cells, except for two additional residues at the carboxyl
      terminus. We confirmed expression of the gene by Northern analysis and by cloning
      a portion of the cDNA from reverse transcribed MG-63 cell RNA. Despite 85%
      identity of the first 270 nucleotides 5' of the transcription start sites, GCP-2
      and ENA-78 show cell-specific differences in regulation. GCP-2 is induced in MG
      63, but not A549 cells by TNF-alpha, IL-1beta, and LPS, while ENA-78 is expressed
      in both cell types. Analysis of nucleotide sequence relationships does not
      support the proposal, by others, that LIX is murine GCP-2. LIX is no more closely
      related to human GCP-2 than to human ENA-78 and is more distant from both human
      genes than is porcine alveolar macrophage chemotactic factor-II.

PMID- 9164945
TI  - IL-6 induction of protein-DNA complexes via a novel regulatory region of the
      inducible nitric oxide synthase gene promoter: role of octamer binding proteins.
AB  - Macrophage inducible nitric oxide synthase (iNOS) catalyzes the synthesis of NO.
      IL-6-stimulated macrophage differentiation of murine myeloid M1 cells is
      accompanied by iNOS gene induction and steady-state mRNA expression. Two regions
      within the iNOS promoter mediate transcriptional responsiveness to LPS and IFN
      gamma. Region I contains several essential transcription factor binding motifs
      and promotes responsiveness to LPS, whereas region II potentiates the LPS
      response by IFN-gamma. Because region I possesses basal promoter activity and
      directly mediates iNOS gene activation, we attempted to identify the trans-acting
      factors involved in IL-6-stimulated induction of the murine iNOS gene through
      this region. Using an electrophoretic mobility shift assay and methylation
      interference, we show that IL-6 induced reciprocal changes in the binding
      activity of POU family members to the candidate nonconsensus octamer sequence of
      region I that correlated, temporally, with iNOS steady-state mRNA expression.
      Although DNA-protein binding activity of IL-6-stimulated whole-cell extracts also
      interacted with a radiolabeled canonical octamer motif, such DNA-protein
      complexes were not eliminated in competition assays using consensus nuclear
      factor kappaB or IL-6 oligonucleotides. Specifically, our studies show that
      octamer binding protein-1-related protein binding activity decreased, while
      binding of octamer binding protein-2-related proteins increased during
      differentiation. Mutation of the octamer motif disrupted both binding of the IL-6
      induced protein-DNA interactions and transcriptional activation through region I,
      revealing that this motif is absolutely essential for IL-6 induction of iNOS.
      Thus, differential activation of octamer binding transcriptional modulators from
      the POU family may be a novel mechanism of IL-6-mediated iNOS gene regulation.

PMID- 9164946
TI  - The mouse anaphylatoxin C3a receptor: molecular cloning, genomic organization,
      and functional expression.
AB  - The anaphylatoxin C3a receptor (C3aR) is unique among the family of G protein
      coupled receptors in possessing an unusually large predicted second extracellular
      loop. To isolate the mouse C3aR, a probe derived from this extracellular loop was
      used to screen a mouse brain cDNA library. A 3.3-kb cDNA encoding an open reading
      frame of 477 amino acids was identified. The predicted amino acid contained four
      predicted N-linked glycosylation sites and was 65% identical to the 482 amino
      acids comprising the coding region of the human C3aR. Northern blot analysis
      revealed that this gene was expressed in a variety of mouse tissue and was
      especially abundant in heart and lung tissues. The mouse C3aR cDNA was used as a
      probe to isolate a mouse C3aR genomic clone. The nucleotide sequence of the mouse
      C3aR genomic clone was identical to the cDNA throughout the coding region,
      indicating that the receptor is encoded on a single exon. The C3aR cDNA was
      subcloned into a mammalian expression vector and transiently expressed in HEK-293
      cells. Binding of radiolabeled C3a to the transfected cells was competed in a
      dose-dependent manner by increasing concentrations of unlabeled C3a, with a 50%
      inhibiting concentration of 10 nM. Similar to the human C3aR, RBL-2H3 rat
      basophilic cells stably expressing this receptor responded in a dose-dependent
      manner to C3a, a synthetic C3a peptide agonist, but not C4a or C5a, with a
      vigorous calcium mobilization.

PMID- 9164947
TI  - Perforin, Fas/Fas ligand, and TNF-alpha pathways as specific and bystander
      killing mechanisms of hepatitis C virus-specific human CTL.
AB  - In chronic hepatitis C, Fas expression is up-regulated in the hepatocytes,
      especially near liver-infiltrating lymphocytes, and Fas ligand is expressed on
      the lymphocytes. The presence of hepatitis C virus (HCV)-specific CTLs has been
      demonstrated both in peripheral blood and among liver-infiltrating lymphocytes of
      patients with chronic hepatitis C. We studied the killing mechanisms of HCV
      specific human CTLs using target cells that were sensitive or resistant to
      agonistic anti-Fas Abs and TNF-alpha. We show that HCV-specific CTL clones kill
      non-Ag-bearing bystander cells as well as Ag-bearing cells, although the
      bystander killing is less efficient than the specific target cell killing, and
      the efficacy of the bystander killing of anti-Fas- and soluble TNF-alpha
      sensitive cells is greater than that of resistant cells. We also show that the
      killing of Ag-presenting, sensitive cells is mediated by Fas ligand and TNF-alpha
      as well as perforin, although the latter plays a major role in the killing at a
      low E:T ratio, and that the killing of sensitive bystander cells is primarily
      mediated by Fas ligand and TNF-alpha on CTLs expressed upon specific Ag
      stimulation, which may be relevant to the bystander lysis by HCV-specific CTLs of
      uninfected hepatocytes, in which Fas expression is up-regulated. Activated CTLs
      also kill bystander cells by the perforin-based mechanism, although it requires a
      high E:T ratio. The effective bystander killing requires a close intercellular
      contact between CTLs and target cells, although TNF-alpha released from the CTLs
      mediates lysis of the bystander cells without a close cell-cell contact.

PMID- 9164949
TI  - Impaired macrophage listericidal and cytokine activities are responsible for the
      rapid death of Listeria monocytogenes-infected IFN-gamma receptor-deficient mice.
AB  - IFN-gamma receptor-deficient (IFN-gammaR -/-) mice were used to study the innate
      immune responses during infection with Listeria monocytogenes. Mutant mice were
      unable to limit bacterial growth and died of sepsis even with an infection dose
      of 70 Listeria. At day 2, they showed an exacerbated listeriosis and mice
      succumbed to infection before the onset of an effective specific immunity,
      demonstrating a defective innate immunity. Recruitment and extravasation of
      phagocytic cells to infected organs was present and dominated by neutrophils.
      However, during the early course of infection, mutant mice responded by an
      elevated inflammatory type 1 cytokine response, as determined by IL-12, IFN
      gamma, TNF-alpha, and IL-1alpha-specific RNA expression. Induction of inducible
      nitric oxide synthase was present and also increased in mutant mice.
      Interestingly, IFN-gammaR -/- neutrophils expressed substantial TNF-alpha- and IL
      1alpha-specific RNA, suggesting a substantial contribution in the overall
      inflammatory cytokine response. In contrast, IFN-gammaR -/- macrophages showed
      reduced MHC class II surface expression levels and impaired TNF-alpha and IL
      1alpha but normal IL-6 production after restimulation with heat-killed L.
      monocytogenes. Moreover, IFN-gammaR -/- macrophages showed defective listericidal
      activities. In contrast to normal macrophages, Listeria escaped rapidly from the
      phagosome in IFN-gammaR -/- macrophages to the cytoplasm, where they productively
      survived. In conclusion, these data suggest that IFN-gammaR signaling activates
      yet unknown functions in macrophages, preventing Listeria-induced escape from the
      phagosome and consequent killing of the invader. Together with the impaired
      cytokine responses, these macrophage defects seem to be responsible for the
      dramatic susceptibility during innate immunity, whereas predominant neutrophil
      responses mediate limited protective role in mutant mice.

PMID- 9164948
TI  - Sequential development of structural and functional alterations in T cells from
      tumor-bearing mice.
AB  - The TCR alpha beta or -gamma delta chains bind the peptide ligand, whereas the
      associated CD3 delta epsilon gamma and TCR zeta subunits couple the TCR to
      intracellular signal transduction components. Recently, several groups have
      described marked alterations in signal transduction elements in T cells from
      cancer patients or in mice bearing tumor for a few weeks (>26 days). The sequence
      in which these alterations develop is unknown. The aim of this study was to
      explore the kinetics of the development of alterations in signal transduction
      molecules (TCR zeta chain, NF kappaB family proteins, and tyrosine kinase
      p56(lck)) in mice bearing MC38 colon adenocarcinoma. The results demonstrate that
      alterations in NF kappaB family proteins, specifically the failure of p65
      translocation to the nucleus, occur earlier and more frequently than the decrease
      in zeta-chain. These defects are paralleled by an impaired ability to produce Th1
      cytokines (IL-2 and IFN-gamma). These initial changes are followed by the
      eventual loss of TCR zeta chain and p56(lck) and a marked decrease in cytotoxic
      function. An increased rate of lysosomal degradation is one of the mechanisms
      responsible for the loss of zeta-chain.

PMID- 9164950
TI  - Listeria monocytogenes infection of cultured endothelial cells stimulates
      neutrophil adhesion and adhesion molecule expression.
AB  - Microbial infection of the endothelium with the resultant up-regulation of
      adhesion molecule expression and stimulated leukocyte adhesion to endothelial
      cells can promote an inflammatory response. Previous work demonstrated that
      Listeria monocytogenes can replicate within cultured endothelial cells; thus, we
      tested whether L. monocytogenes infection of HUVEC stimulated an inflammatory
      phenotype on these cells. Infection with 10(4) CFU of bacteria increased
      neutrophil adhesion to HUVEC 40-fold and up-regulated E-selectin, intercellular
      adhesion molecule-1, and vascular cell adhesion molecule-1 expression.
      Approximately 80% of neutrophil adhesion to infected HUVEC was blocked by anti-E
      selectin mAb, 35% was blocked by anti-CD18 mAb, and anti-vascular cell adhesion
      molecule-1 mAb was without effect. Microscopy of infected HUVEC monolayers showed
      that neutrophils bound to infected and uninfected cells and that infected and
      uninfected HUVEC expressed E-selectin. Interestingly, uninfected HUVEC that bound
      neutrophils or expressed E-selectin typically were adjacent to infected cells.
      However, infected monolayers did not produce soluble factors that stimulated E
      selectin expression on uninfected cells. Nuclear translocation of the p65 subunit
      of the transcription factor NF-kappaB accompanied the HUVEC response, and
      hemolysin secretion appeared critical for stimulating HUVEC. These studies show
      that L. monocytogenes infection stimulates up-regulation of adhesion molecule
      expression on endothelial cells, resulting in neutrophil adhesion to them. This
      response includes induction of an inflammatory phenotype on uninfected cells and
      may be triggered by listeriolysin O-mediated activation of host response
      mechanisms. Additionally, cell-to-cell spread of L. monocytogenes throughout the
      monolayer, without stimulating secondarily infected endothelial cells for
      neutrophil adhesion, is a possible means of immune avoidance.

PMID- 9164951
TI  - Role of T lymphocyte subsets in immunity to spotted fever group Rickettsiae.
AB  - To evaluate the roles of CD4 and CD8 T lymphocytes in immunity to disseminated
      endothelial infection with Rickettsia conorii (Malish 7 strain), these T cell
      subsets were depleted or adoptively transferred into subsequently infected
      C3H/HeN mice. CD4 T lymphocyte-depleted and sham-depleted mice underwent a
      similar course of illness with a sublethal rickettsial dose, cleared the
      infection by day 10, and recovered on days 10 to 11. In contrast, mice depleted
      of CD8 lymphocytes or CD4 and CD8 lymphocytes died or remained persistently
      infected through day 15 with the ordinarily sublethal dose. Endothelium was the
      major site of rickettsial persistence, including sites in the vital organs,
      brain, and lungs of CD8 lymphocyte-depleted mice. In nondepleted animals, CD8 T
      lymphocytes were observed in apposition to endothelial cells on day 10 at the
      time of rickettsial clearance. Adoptive transfer of immune CD4 or CD8 T
      lymphocytes protected mice against a lethal dose of R. conorii in the
      disseminated endothelial target model. Nonimmune CD4 or CD8 lymphocytes and
      immune lymphocytes that had passed through columns that depleted both CD4 and CD8
      lymphocytes failed to protect mice against R. conorii. These studies represent
      the first analysis of the role of T lymphocyte subsets in immunity to spotted
      fever group rickettsiae and the first demonstration that clearance of spotted
      fever group rickettsiae from endothelial cells requires immune CD8 T lymphocytes.

PMID- 9164952
TI  - Oral immunization with simian immunodeficiency virus p55gag and cholera toxin
      elicits both mucosal IgA and systemic IgG immune responses in nonhuman primates.
AB  - Rhesus macaques were orally immunized with a mucosal vaccine consisting of two
      different concentrations (1 mg vs 250 microg) of recombinant SIV p55gag (p55)
      with or without cholera toxin (CT, 50 microg) as a mucosal adjuvant. The plasma
      from macaques receiving the higher dose of p55 (1 mg) and CT had higher p55
      specific IgG and IgA Ab titers compared with macaques that received the lower
      dose of p55 (250 microg) and CT. Further, high levels of p55-specific IgG and IgA
      Abs were present in external secretions from both groups. The level of p55
      induced T cell responses was elevated in PBMCs isolated from the high dose group
      compared with the low dose group. When culture supernatants from these p55
      stimulated PBMCs were examined for Th1 (IFN-gamma) and Th2 (IL-4 and IL-10)
      cytokines, both IFN-gamma and IL-10 were present, but IL-4 was absent. CD4+ T
      cells isolated from these p55-stimulated PBMCs contained IFN-gamma spot-forming
      cells (SFCs) but not IL-4 SFCs. These results were further confirmed by cytokine
      specific reverse transcriptase PCR analysis, where p55-specific CD4+ T cells
      expressed mRNA for IFN-gamma, IL-6, and IL-10, but not IL-4. These findings
      suggest that oral immunization of nonhuman primates induced both IFN-gamma
      secreting Th1 and select Th2 cytokine (e.g., IL-6 and IL-10)-producing CD4+ Th
      cells, which accounted for the generation of p55-specific systemic and mucosal Ab
      responses.

PMID- 9164953
TI  - Protection of mice against Trypanosoma cruzi by immunization with paraflagellar
      rod proteins requires T cell, but not B cell, function.
AB  - Previous studies have shown that immunization of mice with the paraflagellar rod
      proteins (PAR) of Trypanosoma cruzi induces an immune response capable of
      protecting mice against an otherwise lethal challenge with this parasite. Herein,
      we define immunologic responses that do or do not play a critical role in PAR
      mediated protection. Firstly, PAR-immunized Ab-deficient (muMT) strain mice
      survived an otherwise lethal T. cruzi challenge, indicating that a B cell
      response is not required for PAR-induced immunity. However, beta2m -/- mice,
      which are severely deficient in MHC class I and TCR alphabeta+ CD8+ CD4- T cells,
      did not survive challenge infection following PAR immunization, indicating that
      MHC class I/CD8+ T cell function is necessary for protection induced by PAR
      immunization. Surprisingly, PAR-immunized mice depleted of CD4+ T cells survived
      a T. cruzi challenge for >84 days postinfection while maintaining a parasitemia
      that is generally thought to be lethal (i.e., >10(6) trypomastigotes/ml), thus
      associating CD4+ T cell function with the process of parasite clearance.
      Consistent with this association, CD4+ T cells from PAR-immunized mice released
      INF-gamma and stimulated T. cruzi-infected macrophages to release nitric oxide.
      The importance of IFN-gamma in PAR-induced protective immunity is further
      indicated by the observation that PAR-immunized INF-gamma knockout mice developed
      an extremely high parasitemia and did not survive a challenge infection. Thus,
      while Ab-mediated immune mechanisms are not required for protection induced by
      PAR immunization, T cell responses are necessary for both elimination of
      bloodstream parasites and survival.

PMID- 9164954
TI  - Involvement of NK1+ CD4- CD8- alphabeta T cells and endogenous IL-4 in non-MHC
      restricted rejection of embryonal carcinoma in genetically resistant mice.
AB  - Non-MHC-restricted rejection mechanisms against the murine MHC-negative F9
      embryonal carcinoma cells were analyzed. Strains of C57BL/6 (B6) background were
      resistant to the tumors irrespective of H-2 haplotypes, while others, including
      BALB/c background, were susceptible. This resistance was suggested to be mediated
      primarily by the host thymus-dependent alphabeta T cells, since both athymic B6
      nude and normal B6 mice depleted with alphabeta T cells showed susceptible
      phenotype. The difference of the nature of alphabeta T cells infiltrating in H-2
      identical B6- and BALB.B-derived tumors was then comparatively analyzed. It was
      revealed that unique T cells with NK1+ CD4- CD8- (double negative (DN)) alphabeta
      TCR+ phenotype were accumulated significantly in B6, but few in BALB.B mice. The
      population freshly isolated from the F9 tumor tissues preferentially expressed
      potent IL-4 mRNA, and was suggested to be mostly responsible for the endogenous
      IL-4 production. Indeed, the injection of either anti-NK1.1 or anti-IL-4
      neutralizing Ab into the normal B6 rendered them significantly susceptible to the
      tumor cells. These results strongly suggested that NK1+ DN alphabeta T cells were
      responsible primarily for the rejection mechanisms against F9 tumors.
      Histologically, F9 tumors in B6 mice were characterized by abundant macrophage
      infiltration and massive tumor necrosis, neither of which was observed in those
      in BALB.B nor B6 mice preinjected with anti-IL-4 Ab, indicating that both
      histologic features in the resistant strain were dependent on the endogenous IL
      4. Present results provide one of the first instances in which a recently
      emerging minor T cell subpopulation, thymus-dependent NK1+ DN alphabeta T cells,
      plays an essential role in anti-tumor responses in vivo.

PMID- 9164955
TI  - Neutrophil production of IL-12 and IL-10 in candidiasis and efficacy of IL-12
      therapy in neutropenic mice.
AB  - Neutrophil defects predispose to severe fungal infections, yet the
      immunomodulatory role of these cells is poorly defined. The contribution of
      neutrophils to the early cytokine balance governing Th1 and Th2 cell development
      was examined in mice with candidiasis. Neutrophils secreted IL-12 and IL-10,
      correlating with the respective development of self-limiting (Th1-associated) and
      progressive (Th2-associated) disease. Exogenous IL-12 was effective in protecting
      neutropenic hosts susceptible to infection. These results suggest that 1)
      neutrophils, via their ability to release cytokines, play an active role in
      determining the qualitative development of the T cell response, and 2) their
      early role in anticandidal immunity can be replaced by exogenous IL-12.

PMID- 9164956
TI  - Protective effect of neoglycoprotein-conjugated muramyl dipeptide against
      Leishmania donovani infection: the role of cytokines.
AB  - Active targeting of muramyl dipeptide (MDP) to macrophages was studied by
      conjugation with the neoglycoprotein, mannosyl human serum albumin (mannose-HSA)
      using visceral leishmaniasis as the model macrophage disease. Conjugation did not
      decrease the affinity of the neoglycoprotein for macrophage mannose receptor.
      Mannose-HSA-MDP was 50 times more efficient than free MDP in inhibiting the
      growth of Leishmania donovani inside peritoneal macrophages. Moreover, in a 60
      day murine model of visceral leishmaniasis, 95% of the spleen parasite burden was
      reduced by mannose-HSA-MDP at a dose of 0.5 mg/kg/day given for 4 days. Free MDP
      at a similar dose had very little effect. In vitro exposure of MDP caused
      enhanced generation of O2- by macrophages, whereas generation of nitric oxide
      (NO) was not induced. The elevated antileishmanial activity of MDP-treated
      macrophages in culture was abrogated by O2- scavengers. In contrast, considerably
      enhanced amounts of NO and O2- were generated from macrophages of mannose-HSA-MDP
      treated animals, and their splenocytes secreted soluble factors providing all the
      signals required for the induction of NO biosynthesis. The increase in NO
      production was paralleled by a concomitant increase in antileishmanial activity,
      which was reversed by NO synthesis inhibitors. Splenocyte supernatants treated
      with anti-IFN-gamma or anti-TNF-alpha Abs suppressed inducible NO generation by
      macrophages. Moreover, i.v. administration of anti-IFN-gamma and anti-TNF-alpha
      along with mannose-HSA-MDP greatly reduced protection against L. donovani
      infection. Neoglycoprotein-conjugated MDP, therefore, activated mouse macrophages
      in vivo to kill L. donovani, and this may depend on the physiologic generation of
      NO induced by IFN-gamma and TNF-alpha.

PMID- 9164957
TI  - Cytolytically active memory CTL present in lymphocytic choriomeningitis virus
      immune mice after clearance of virus infection.
AB  - Generally, it has been assumed that memory T cells are dormant and inactive cells
      in the absence of their specific Ag. Recent work has challenged this assumption
      by showing that a portion of the CD8+ memory T cell pool is in cycle. In this
      study, we demonstrate that a significant number of blast-size memory CD8+ T cells
      in mice, long after lymphocytic choriomeningitis virus (LCMV) infection, mediate
      cytolysis against highly sensitive targets without any in vivo or in vitro
      restimulation and expansion with Ag. Peptide-coated RMA-S targets were
      sufficiently sensitive to detect low but significant cytolytic activity in bulk
      51Cr release assays in nonstimulated LCMV-specific splenic memory CTL
      populations. Most of the directly cytotoxic activity was against the GP33
      epitope, and this persisted throughout the lifetime of the mouse following
      infection. The cytotoxic activity was not inhibited by cyclosporin A, indicating
      that these cells were already in an active state and not dependent on further
      stimulation in vitro. It was formally shown that the cytotoxic activity was
      mediated by the CD8+ CTL by sorting for the blast-size CD8+ population and by
      blocking target cell lysis with anti-CD8 Ab. Thus, at any time after the original
      infection some portion of the memory CD8+ T cell pool is cycling, and it remains
      cytolytically active long after resolution of the original infection. These CTL
      may provide a rapidly acting defense mechanism against reinfection.

PMID- 9164958
TI  - Role of CD4+ T cells in pathogenesis associated with Leishmania amazonensis
      infection.
AB  - Most inbred strains of mice are susceptible to Leishmania amazonensis infection.
      We have examined the mechanism(s) underlying this generalized susceptibility
      using mice deficient in T cell development or in the expression of either MHC
      class I or class II. In contrast to wild-type C57BL/6 (B6) mice that uniformly
      developed large ulcerating lesions, mice lacking functional CD4+ T cells (due to
      targeted disruption of genes for either MHC class II trans-activator or I-A beta)
      showed no signs of lesion development for up to 12 to 14 wk postinfection and
      contained significantly lower numbers of parasites in lesions. Similarly, both B6
      nude and RAG2 -/- mice failed to develop lesions. However, RAG2 -/- mice
      reconstituted with naive wild-type CD4+ T cells and beta2m -/- mice did develop
      lesions. Lesions of MHC class II -/- mice contained minimal numbers of CD8+ T
      cells, a marked reduction of monocytes/macrophages, and evident extracellular
      parasites. The inability to mount an inflammatory response in MHC class II -/-
      mice correlated with the failure to produce lymphokines that lead to the
      recruitment of monocytes/granulocytes. These results demonstrate that CD4+ T
      cells are the primary lymphocyte subset that mediates cellular infiltration,
      lesion pathology, and therefore, susceptibility to L. amazonensis infection. The
      disease-promoting CD4+ T cells in L. amazonensis-infected mice have the
      characteristics of Th1 cells. The striking differences in the course of infection
      between MHC class II -/- mice infected with L. amazonensis and Leishmania major
      suggest that these parasites may have adapted different strategies regarding the
      CD4-dependent immune response.

PMID- 9164959
TI  - Role of a sialyl Lewis(x)-like epitope selectively expressed on vascular
      endothelial cells in local skin inflammation of the rat.
AB  - The role of the inducible L-selectin ligand was studied in complement-dependent
      acute dermatitis in rats. Although mAbs against typical sialyl Lewis(x) (CSLEX-1
      and SNH-3) did not react with skin venules, a sialyl Lewis(x)-like epitope
      defined by mAb 2H5 (2H5-Ag) was de novo expressed on the endothelial cells of
      skin venules in the area of inflammation. Expression of 2H5-Ag increased
      concomitantly with the progression of inflammation. 2H5-Ag was identified at the
      75-, 150-, and 180-kDa bands when inflammatory skin tissue was analyzed by
      Western blotting. In contrast, P- and E-selectins were not detectable. The role
      of 2H5-Ag in this model was studied in in vitro and in vivo methods. First, 2H5
      was i.v. injected 15 min before induction of dermatitis. 2H5 bound to skin
      venules and significantly reduced the neutrophil infiltration and plasma protein
      leakage. In contrast, CSLEX-1, mAb ARP2-4 (P-selectin blocker), or mAb ARE-5 (E
      selectin blocker) had no effects. Second, adhesion of isolated rat neutrophils to
      the inflammatory skin section was inhibited significantly when the sections, but
      not neutrophils, were preincubated with 2H5. Third, fluorescein-labeled normal
      rat neutrophils were injected into a rat 10 h after induction of dermatitis. The
      number of labeled neutrophils infiltrated into the inflammatory site was reduced
      significantly when they were preincubated with HRL-3 (blocking mAb against rat L
      selectin), but not with 2H5 or HRL-4 (nonblocking mAb against rat L-selectin).
      These data show that de novo expressed 2H5-Ag/L-selectin adhesion pathway
      contributes to the development of acute complement-dependent inflammation in the
      skin.

PMID- 9164961
TI  - Adenosine inhibits neutrophil degranulation in activated human whole blood:
      involvement of adenosine A2 and A3 receptors.
AB  - Adenosine, acting via A2 receptors, is a potent inhibitor of neutrophil oxidative
      burst, but its effects and mechanisms of action on neutrophil degranulation have
      been less well characterized. We, therefore, investigated the effects of
      adenosine and its receptor-specific analogues on neutrophil degranulation in
      stimulated human whole blood. Adenosine dose-dependently inhibited the LPS- and
      TNF-alpha-induced release of the azurophilic granule proteins
      bactericidal/permeability-increasing protein, elastase, and defensins to
      approximately the same extent, with a maximum inhibition of 70 to 80% and an IC50
      ranging from 14 to 24 microM. The inhibitory effects of adenosine were partially
      blocked by the A2 receptor antagonist 3,7-dimethyl-1-propargylxanthine, the A1/A2
      antagonist 8(p-sulfophenyl)theophyline, and the A1/A3 antagonist xanthine amine
      congener, but not by the A1 antagonist 1,3-dipropyl-8-cyclopentylxanthine. The
      highly selective A3 agonist N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide and
      the nonselective agonist 2-chloroadenosine reduced degranulation more potently
      than the A1 agonist N6-cyclopentyladenosine. The inhibitory effects of N6-(3
      iodobenzyl)-adenosine-5'-N-methyluronamide and 2-chloroadenosine were strongly
      reversed by xanthine amine congener, but were not affected by 8(p
      sulfophenyl)theophyline. In addition, the adenosine kinase inhibitor GP515
      attenuated degranulation via an adenosine-mediated mechanism. These data indicate
      that adenosine acts via A2 as well as A3 receptors to inhibit neutrophil
      degranulation and add to the anti-inflammatory potential of adenosine and
      adenosine-regulating agents in neutrophil-mediated tissue injury.

PMID- 9164960
TI  - Ultraviolet light suppresses IFN-gamma-induced IL-7 gene expression in murine
      keratinocytes by interfering with IFN regulatory factors.
AB  - UV light is a potent stimulus for keratinocytes to release several cytokines.
      Recently, UV light was shown to inhibit keratinocyte release of IL-7, a growth
      factor for dendritic epidermal T cells. Since to date IL-7 is the only
      keratinocyte-derived cytokine down-regulated by UV light, we addressed the
      molecular mechanisms involved. IFN-gamma treatment of the murine keratinocyte
      cell line Pam 212 resulted in an up-regulation of IL-7 mRNA, while IL-7
      transcripts were suppressed in cells exposed to UV before IFN-gamma. Because IFN
      gamma induces IL-7 via activation of an IFN-stimulated response element (ISRE)
      located in the 5' upstream region of the IL-7 gene, bandshift assays were
      performed using the ISRE sequence from the IL-7 gene. Nuclear extracts from
      untreated cells revealed two bands, a slower migrating band identified by
      supershift analysis as IFN regulatory factor-2 (IRF-2), a transcriptional
      repressor, and a more rapidly migrating band identified as IRF-1, a
      transcriptional activator. IFN-gamma significantly induced IRF-1 binding, whereas
      UV treatment plus IFN-gamma decreased IRF-1 binding, suggesting that UV light
      suppresses IFN-gamma-induced expression of IL-7 by interfering with IRF-1.
      Chloramphenicol transferase assay confirmed functional relevance, showing that
      the minimal promoter sequence for the ISRE explicitly responded to IFN-gamma,
      which was suppressed by UV irradiation. Northern blot analysis using an IRF-1
      cDNA probe revealed that UV light reduced IFN-gamma-induced IRF-1 mRNA. This
      study demonstrates that UV light can inhibit cytokine activities by interference
      with transcriptional activators. This newly described ability of UV light may
      contribute to its immunosuppressive properties.

PMID- 9164962
TI  - Inhibition of CD45 during neutrophil activation.
AB  - Tyrosine phosphorylation represents a balance between the activity of tyrosine
      kinases and phosphatases. We have demonstrated recently that reactive oxygen
      intermediates (ROI) produced by the nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase enhance tyrosine phosphorylation in neutrophils. As tyrosine
      phosphatase activity can be regulated by oxidants, we sought to determine whether
      endogenously generated ROI inhibited the activity of the leukocyte tyrosine
      phosphatase CD45. Addition of guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) to
      electropermeabilized neutrophils, conditions known to activate the oxidase,
      inhibited CD45, as determined by immunoprecipitation and an in vitro phosphatase
      assay. That this inhibition was a consequence of activation of the oxidase was
      supported by three observations: 1) GTPgammaS-induced inhibition of CD45 was
      NADPH dependent; 2) pretreatment of cells with diphenylene iodonium, an oxidase
      inhibitor, partially prevented the inhibition; and 3) inhibition of CD45 was
      diminished markedly in neutrophils from chronic granulomatous disease (CGD)
      patients. The inhibition could be partially prevented by treatment of the cells
      with the antioxidants N-acetylcysteine or DTT, but direct antioxidant treatment
      of CD45 immunoprecipitates could not restore activity. Exposure to PMA, a direct
      activator of protein kinase C that also induces an oxidative burst, inhibited
      CD45 in both normal and CGD neutrophils. However, the magnitude of inhibition was
      less and the kinetics delayed in CGD cells when compared with normal cells. We
      conclude that ROI produced by the NADPH oxidase can contribute to inhibition of
      tyrosine phosphatases such as CD45 by oxidant-mediated effects, but that
      alternate regulatory mechanisms also exist.

PMID- 9164963
TI  - N-acetylcysteine and alpha-tocopherol reverse the inflammatory response in
      activated rat Kupffer cells.
AB  - Activation of the resident macrophage populations of the reticuloendothelial
      system is a key component of the complex pathophysiology of sepsis. Macrophage
      activation leads to production and secretion of inflammatory mediators such as
      cytokines, vasoactive substances, free radicals, and chemokines, which have been
      associated with high morbidity and mortality in the septic patient. The goal of
      the present study was to determine whether antioxidants could suppress Kupffer
      cell activation at points beyond the initiation of activation. Kupffer cells were
      studied since they are central to the clearance of bacteria and endotoxins, and
      have been associated with hepatocellular dysfunction in sepsis. Cells were
      activated with 10 ng/ml LPS for various times whereupon N-acetylcysteine (30 mM)
      and alpha-tocopherol (50 microM) were added. Steady state levels of cytokine
      mRNA, activation of nuclear factor-kappaB, and TNF-alpha secretion were
      determined when expression was maximal in control cells. The results of this
      study show that antioxidants can be used to suppress Kupffer cell activation at
      points beyond the initiation of activation. Furthermore, we show that N
      acetylcysteine-mediated inhibition of activation requires secondary protein
      synthesis, but does not modulate IkappaB-alpha mRNA expression. The inhibitory
      effect of these drugs occurs at the very earliest steps of the LPS signal
      transduction cascade as it is currently understood. The results of the present
      study suggest that the inflammatory response to sepsis may be controlled through
      appropriate antioxidant therapy.

PMID- 9164964
TI  - Tyrosine kinase-dependent regulation of L-selectin expression through the Leu-13
      signal transduction molecule: evidence for a protein kinase C-independent
      mechanism of L-selectin shedding.
AB  - The L-selectin adhesion molecule mediates lymphocyte extravasation in peripheral
      lymph nodes, and has also been implicated in directing leukocyte recruitment to
      inflammatory tissues and metastasis of lymphoid malignancies. In this study, we
      demonstrate a novel level of regulation of L-selectin expression that involves
      the 16-kDa Leu-13 signal transduction molecule. Leu-13 is a member of a
      multimeric cell surface complex in lymphocytes that includes TAPA-1 (target of
      antiproliferative Ab-1, CD81) as well as lineage-specific proteins. In the
      present study, mAb-induced ligation of Leu-13 was shown to rapidly down-regulate
      L-selectin surface density on normal and malignant human lymphocytes, and to
      markedly inhibit L-selectin-mediated adhesion of lymphocytes to soluble
      carbohydrate ligands (i.e., PPME, phosphomonoester core polysaccharide) and to
      lymph node high endothelial venules. Through the use of genistein and
      staurosporine, potent inhibitors of tyrosine kinases (TK) and protein kinase C
      (PKC), respectively, Leu-13-induced L-selectin down-modulation was demonstrated
      to involve a TK-dependent, PKC-independent pathway, and was attributed to
      increased L-selectin shedding from surface membranes. Notably, direct L-selectin
      ligation, modeling cross-linking interactions with endothelial cell ligands,
      similarly down-regulates L-selectin surface expression through a TK-dependent,
      PKC-independent mechanism. In sharp contrast, PMA and anti-CD3 mAb down-regulate
      L-selectin via a staurosporine-sensitive, genistein-resistant pathway that is
      closely linked to lymphocyte proliferation. Taken together, these results
      demonstrate a novel role for Leu-13- and L-selectin-induced TK activity in
      control of L-selectin expression, thus providing insight into the complex
      molecular mechanisms that potentially regulate L-selectin-dependent lymphocyte
      homing in vivo.

PMID- 9164965
TI  - Thrombin induces endothelial type II activation in vitro: IL-1 and TNF-alpha
      independent IL-8 secretion and E-selectin expression.
AB  - In addition to its role in coagulation, thrombin is involved in the inflammatory
      process by inducing vessel neutrophilic infiltration. Thrombin induces
      endothelial P-selectin expression and platelet activating factor release, which
      participate to induce early neutrophil adhesion and activation. We employed HUVEC
      and now show that thrombin induces the production of the chemokine IL-8 in a time
      and dose-dependent fashion. Similarly, thrombin induced E-selectin expression on
      HUVEC. Both IL-8 secretion and E-selectin expression were preceded by an increase
      in steady state levels of the respective mRNAs. Thrombin action on HUVEC was
      inhibited by the specific thrombin inhibitor, hirudin. In addition, these effects
      of thrombin on HUVEC were mimicked by the 14-amino acid thrombin receptor agonist
      peptide, which triggers the native thrombin receptor in a similar fashion to
      thrombin itself. Although IL-1 and TNF-alpha also induce IL-8 and E-selectin, the
      thrombin effects in these experiments were not mediated by those cytokines, since
      neither IL-1 receptor antagonist nor anti-TNF-alpha Ab inhibited the effects of
      thrombin. Furthermore, IL-1alpha, IL-1beta, and TNF-alpha were not detected in
      the supernatants of thrombin-activated HUVEC. Although intracellular IL-1alpha
      was found in thrombin-activated HUVEC, antisense IL-1alpha had no inhibitory
      effect on IL-8 secretion. These results demonstrate that in addition to short
      term endothelial activation, thrombin also functions as a long acting
      proinflammatory agent by inducing endothelial synthesis of the mediators required
      for neutrophils activation and extravazation during inflammation.

PMID- 9164966
TI  - Human alveolar macrophages synthesize endothelins by thrombin.
AB  - Alveolar macrophages (AM) play pivotal roles in the defense mechanism and the
      regulation of inflammatory processes in the airways. Macrophages express
      receptors for thrombin on their surfaces, and thrombin induces the chemotaxis and
      the proliferation of macrophages. Thrombin acts on vascular endothelial cells to
      synthesize endothelin (ET)-1. AM have been known to express prepro ET-1 mRNA.
      Thus, we hypothesized that thrombin stimulates AM so as to synthesize ET.
      Surgically resected human lungs were irrigated by saline to remove intravascular
      blood, then saline was instilled into the bronchus, and the fluids were
      recovered. AM were separated by Percoll density centrifugation (density, 1.060
      g/ml). AM were resuspended in culture medium without FCS in the presence or
      absence of thrombin. ET was synthesized by thrombin in a concentration-dependent
      manner, and the amounts of ET synthesized by thrombin (10 U/ml) were equivalent
      to those by LPS (10 microg/ml). Dexamethasone (10(-6)-10(-10) M), IL-4 (100
      U/ml), and TGF-beta (10 ng/ml) significantly suppressed the ET synthesis by
      thrombin (p < 0.05). In contrast, 1,25-dihydroxyvitamin D3 (10(-8)-10(-10) M)
      enhanced the ET synthesis up to approximately 300%. The analysis using high
      pressure liquid chromatography revealed that AM-derived ET consists of ET-1, ET
      2, and ET-3. Major constituents were ET-2 and ET-1, and the ratio of ET-2/ET-1
      was 1.7 +/- 0.4 (mean +/- SE). These results indicate that thrombin is a potent
      agonist for AM to synthesize ET.

PMID- 9164968
TI  - A novel mechanism of alternative pathway complement activation accounts for the
      deposition of C3 fragments on CR2-expressing homologous cells.
AB  - Complement receptor type 2 (CD21, CR2), the receptor for the C3 fragment C3dg,
      activates complement via the alternative pathway and also serves as a
      preferential acceptor site for C3 fragments. The molecular basis for this
      phenomenon, which has recently been demonstrated for B lymphocytes in vivo, is
      currently not understood. Here we present a model for this CR2-dependent
      complement activation. The inactive C3 (iC3), which forms spontaneously in serum
      in low amounts by reaction of native C3 with H2O, binds noncovalently to the N
      terminal part of CR2. Subsequent association of properdin and factor B, and
      cleavage of factor B by factor D lead to formation of a C3 convertase associated
      with CR2, thus focussing covalent C3 deposition to CR2 itself. This model is
      supported by the following experimental findings. 1) By FACS analysis and
      radioreceptor assays we showed that iC3, properdin, and factor B bound to CR2 on
      Raji B cells, MT2 T cells, and peripheral blood B cells. 2) Both binding of these
      proteins and complement activation by CR2-expressing cells were reduced in
      parallel by Abs against CR2. 3) 125I-labeled C3b was covalently deposited on CR2,
      when hemolytically active 125I-labeled C3 was added to Raji cells preincubated
      with iC3, factor B, properdin, and factor D, thus proving functionality of CR2
      bound C3 convertase. This model of C3 convertase activity formed on CR2 domains
      inaccessible for decay-accelerating factor offers an explanation for the
      deposition of C3 found on CR2-expressing cells.

PMID- 9164967
TI  - Regulation of IgE-dependent IL-4 generation by human basophils treated with
      glucocorticoids.
AB  - Glucocorticoids are widely used in the therapeutic intervention of allergic
      diseases, affecting the function of a variety of proinflammatory cell types that
      participate in these disorders. These drugs have been shown to inhibit the
      release of histamine by human basophils, but not by mast cells, in a reaction
      requiring 8 to 24 h. To address whether the generation of IL-4 by basophils is
      similarly affected, we investigated the actions of glucocorticoids on the in
      vitro release of this cytokine induced by anti-IgE Ab or by the human recombinant
      histamine-releasing factor. The ability of basophils to generate IL-4 was
      immediately affected, with secretion of this protein being inhibited >50% with <1
      h preexposure to steroid. However, the release of histamine in these cultures was
      inhibited only after 24-h preincubation, suggesting that the mechanisms
      controlling the release of this mediator differ significantly from those
      regulating cytokine secretion. A rank order of potency of the steroids tested for
      inhibition of IL-4 protein was as follows: triamcinolone > dexamethasone >
      betamethasone > hydrocortisone. The sex steroids, testosterone and estrogen,
      showed no effect on basophil secretion. Experiments using reverse transcription
      PCR indicate that glucocorticoids inhibit IL-4 generation in basophils on the
      level of transcription. These studies suggest that the success of glucocorticoids
      in the treatment of allergic conditions is due in part to their ability to
      inhibit both mediator release and cytokine secretion by basophils.

PMID- 9164969
TI  - Eosinophil adhesion regulates RANTES production in nasal epithelial cells.
AB  - Among the many known chemotactic factors for eosinophils, the proinflammatory
      chemokine RANTES is particularly important, because it is potently and
      selectively chemotactic for eosinophils. Throughout the process of the migration
      of eosinophils from the blood vessels into the nasal cavity, eosinophil functions
      are assumed to be regulated by surface adhesion molecules. Conversely, the
      messages conferred by the eosinophils to the endothelial and epithelial cells are
      also of great interest. In the present study, we showed that eosinophil adhesion
      to human nasal epithelial cells (HNECs) inhibits RANTES production in HNECs.
      Eosinophils were isolated from peripheral blood obtained from patients with
      allergic rhinitis. Human mucosal microvascular endothelial cells and HNECs were
      isolated from human nasal mucosa specimens. After stimulation of the HNECs in the
      presence of eosinophils, the secretion of RANTES, induced by a combination of TNF
      alpha and IFN-gamma, appeared to have decreased. The amount of the decrease was a
      function of the number of involved eosinophils. On the other hand, the presence
      of eosinophils did not affect RANTES production by the endothelial cells. After
      pretreatment of the eosinophils with anti-CD18 mAb or coculture with HNECs in
      Transwell culture inserts, these cells did not inhibit the TNF-alpha- and IFN
      gamma-induced RANTES production. These results were virtually identical with
      those observed on RANTES mRNA expression. The adhesion of eosinophils to HNECs
      plays a key role in the inhibition of RANTES production. Our data indicate that a
      certain established system causes the signal transfer from eosinophils to HNECs
      to inhibit RANTES production, thus decreasing the eosinophil infiltration.

PMID- 9164970
TI  - A TCR V alpha CDR3-specific motif associated with Lewis rat autoimmune
      encephalomyelitis and basic protein-specific T cell clones.
AB  - To investigate TCR V alpha gene expression in the Lewis rat model of experimental
      autoimmune encephalomyelitis, we obtained V alpha chain sequences from two V
      beta8.2+-encephalitogenic, BP72-89-specific T cell clones. Two different V alpha
      genes, a V alpha2 gene and a V alpha23 gene, are utilized, but both were found to
      contain an asparagine repeat (Asn3+) sequence present in the V alpha CDR3 region.
      This Asn3+ motif is also present in the previously reported sequence of a BP68-88
      specific hybridoma, 510, which utilizes a different V alpha2 gene family member.
      In further experiments, spinal cord T cells were isolated at the onset of basic
      protein (BP)-induced disease and sorted for the OX-40 activation marker, which we
      have previously used to enrich for specifically activated T cells. Analysis of V
      alpha expression in the OX-40+ population revealed the biased use of three V
      alpha genes, V alpha1, V alpha2, and V alpha23. The Asn3+ motif was present in
      the V alpha CDR3 region of V alpha1, V alpha2, and V alpha23 cDNA derived from OX
      40+ spinal cord T cells but found to be generally absent in the OX-40- spinal
      cord population. Since these Asn3+ motif-bearing V alpha chain sequences are
      nearly identical to those utilized by the BP-specific encephalitogenic clones
      described, it is likely that these V alpha sequences are derived from disease
      associated T cells in the spinal cord. Thus, we demonstrate that the Asn3+ V
      alpha CDR3 motif is strongly associated with experimental autoimmune
      encephalomyelitis in the Lewis rat and propose that it plays a role in TCR
      recognition of a specific BP peptide/MHC complex.

PMID- 9164971
TI  - IFN-gamma is essential for the development of autoimmune glomerulonephritis in
      MRL/Ipr mice.
AB  - MRL/lpr mice develop lymphoproliferation and accelerated autoimmune
      glomerulonephritis from which they ultimately die. To investigate the role of IFN
      gamma in the manifestation of the disease, we generated MRL/lpr mice lacking the
      IFN-gamma receptor (MRL/lpr gammaR -/-). The absence of IFN-gamma signaling had
      no effect on generalized lymphoproliferation, expansion of CD4- CD8- double
      negative T cells, or hypergammaglobulinemia. By contrast, glomerulonephritis as
      detected by proteinuria and histology was absent in MRL/lpr gammaR -/- mice.
      While serum IgG1 anti-dsDNA Abs were increased in all three strains of MRL/lpr
      mice (gammaR +/+, +/-, -/-), those of the IgG2a and IgG3 isotypes were low in
      MRL/lpr gammaR -/- mice. Immune complexes and C3 deposition were dramatically
      reduced in the glomerular capillaries of MRL/lpr gammaR -/- mice compared with
      MRL/lpr gammaR +/+ and +/- mice. Therefore, IFN-gamma plays a key regulatory role
      in the development of nephritis in MRL/lpr mice. Low levels of IFN-gamma
      dependent IgG2a and IgG3 autoantibodies in MRL/lpr gammaR -/- mice might protect
      them from the pathogenic features of IgG3 cryoglobulins and complement-activating
      IgG2a and IgG3.

PMID- 9164972
TI  - Concomitant killing in vitro of both gp120-coated CD4+ peripheral T lymphocytes
      and natural killer cells in the antibody-dependent cellular cytotoxicity (ADCC)
      system.
AB  - NK cells play an important immunoregulatory role in first line defense mechanisms
      against infection. As disease progresses, HIV-1 infected patients show loss of NK
      cytotoxic function, down-modulation and/or loss of expression of both CD16 and
      CD56 surface Ags on NK cells and a gradual loss of both CD4+ T cells and NK cell
      numbers. A potential mechanism by which these manifestations may occur in vivo
      was investigated. We hypothesized that NK-mediated Ab-dependent cellular
      cytotoxicity (ADCC), using gp120-coated CD4+ peripheral T lymphocytes as targets
      and anti-HIV serum, will result in the concomitant killing of the CD4+ T
      lymphocyte targets and the NK lymphocytes. This hypothesis was examined in an in
      vitro model system. The findings demonstrate that gp120-coated peripheral T
      lymphocytes can serve as targets and are killed in ADCC. Further, the NK cells
      that recover from the ADCC reaction show a loss of cytotoxic function, acquire
      the CD16(dim/-) CD56(dim/-) phenotype and a significant fraction is killed by
      activation-induced cell death or apoptosis. These findings are reminiscent of the
      properties of circulating NK cells in HIV-infected patients. The implication of
      these findings in the pathogenesis of AIDS is discussed.

PMID- 9164973
TI  - High susceptibility to collagen-induced arthritis in mice lacking IFN-gamma
      receptors.
AB  - Collagen-induced arthritis (CIA), an animal model for rheumatoid arthritis, is
      induced in DBA/1 (H-2q) mice following immunization with type II collagen (CII)
      in CFA. Since we have previously shown that IFN-gamma exerts a biphasic effect
      during the evolution of CIA in DBA/1 mice, we analyzed the development of this
      disease in mice with a disruption of the IFN-gamma receptor gene (IFN
      gammaR(0/0)). Mutant mice were interbred with the DBA/1 strain to yield IFN
      gammaR(0/0) mice expressing the H-2q haplotype. In three consecutive experiments,
      IFN-gammaR(0/0) male mice were found to exhibit severe clinical and histologic
      arthritis with an average incidence of 88.5 vs 94.1% for the wild DBA/1 strain.
      Notably, onset of clinical symptoms occurred significantly earlier than in DBA/1
      mice. Although of a lower magnitude than in males, CIA also developed early in
      IFN-gammaR(0/0) female mice and with higher clinical severity than in control
      DBA/1 females. Immunization of knockout mice with CII resulted in the generation
      of CII-specific T cells belonging to the Th1 phenotype that recognize the same
      immunodominant peptides as do DBA/1 mice. CIA in IFN-gammaR(0/0) mice was
      associated with a down-regulation of the CII-specific IgG response, and this
      impairment was essentially due to a strong reduction of Abs of the IgG2a isotype.
      Taken together, our findings provide evidence that IFN-gammaR deficiency in DBA/1
      mice leads to the occurrence of severe CIA with an accelerated onset compared
      with that in wild-type mice, indicating that the proinflammatory action of IFN
      gamma has been bypassed in the IFN-gammaR(0/0) mice.

PMID- 9164975
TI  - Macrophage migration inhibitory factor is involved in the pathogenesis of
      collagen type II-induced arthritis in mice.
AB  - To determine the importance of macrophage migration inhibitory factor (MIF) in
      the development of arthritis we used an experimental model for rheumatoid
      arthritis, collagen type II (CII)-induced arthritis in mice. Treatment with
      neutralizing anti-MIF Abs before immunization of (B10.Q x DBA/1)F1 with CII led
      to delayed onset and lowered frequency of arthritis. This was associated with
      lower levels of IgG2a to CII in MIF-depleted mice. The proliferative response to
      CII was stronger in the anti-MIF-treated mice, whereas no significant effects
      were seen on Ag-induced IFN-gamma production in response to CII or on the total
      serum Ab levels in response to CII. These results provide the first experimental
      evidence of a role for MIF in the pathogenesis of autoimmune disease.

PMID- 9164974
TI  - Accelerated collagen-induced arthritis in IFN-gamma receptor-deficient mice.
AB  - Collagen-induced arthritis (CIA) is a model for rheumatoid arthritis. Here, we
      describe experiments showing that IFN-gamma receptor knockout (IFN-gammaR alpha
      KO) mice of the DBA/1 strain develop CIA more readily than their wild-type
      counterparts. Symptoms of disease started 10 days earlier and the cumulative
      incidence of arthritis was significantly higher in the mutant mice than in wild
      type mice. Similarly, accelerated onset of the disease was also found in wild
      type DBA/1 mice treated with neutralizing mAbs against IFN-gamma. Histologic
      examination of the joints revealed a massive infiltration of the synovium with
      mononuclear cells and neutrophils, hyperplasia, and severe pannus formation in
      IFN-gammaR alpha KO mice when such inflammatory lesions were not yet detectable
      in wild-type mice. Serum levels of anti-collagen type II Abs, including total IgG
      and IgM, as well as IgG1, IgG2a, and IgG2b isotypes were found to be lower in the
      mutant mice. IL-2 and IL-4 remained undetectable in sera of both groups of mice,
      but did appear in the circulation after anti-CD3 Ab challenge. Significantly
      higher IL-2 and lower IL-4 serum levels were found in anti-CD3-challenged IFN
      gammaR alpha KO mice than in wild-type counterparts, both at an early and at a
      later stage of the disease. These observations indicate that endogenous IFN-gamma
      counteracts development of collagen-induced arthritis and suggest that IFN-gamma
      does so by up-regulating IL-4 production and/or down-regulating IL-2 production.
      The data are in line with the concept of a pathogenic role of Th1-type cellular
      immunity in CIA in spite of a decreased Ab response to collagen type II.

PMID- 9164976
TI  - Enhancement of gp130-mediated tyrosine phosphorylation of STAT3 and its DNA
      binding activity in dexamethasone-treated AIDS-associated Kaposi's sarcoma cells:
      selective synergy between dexamethasone and gp130-related growth factors in
      Kaposi's sarcoma cell proliferation.
AB  - The soluble IL-6R (slL-6R alpha)/IL-6 complex and oncostatin M (OM), which exert
      biologic activities through the signal-transducing protein gp130, are potent
      growth factors for AIDS-associated Kaposi's sarcoma (KS) cells. Clinical
      observations indicate that glucocorticoid therapy is a possible risk factor in
      KS; however, little is known of specific interactions in KS cells between
      glucocorticoid and gp130-related growth factors. We obtained evidence that
      dexamethasone (Dex), in a synergistic manner, enhances gp130-mediated growth of
      KS cells. Anti-gp130 Abs or the glucocorticoid antagonist RU-486 abolished this
      synergistic effect. In addition, Dex had additive but not synergistic effects on
      stimulation of KS cell growth with IL-1beta or TNF-alpha, the signals of which
      are not mediated through gp130. Immunoblot analysis revealed sIL-6R alpha/IL-6-
      or OM-induced tyrosine phosphorylation of a similar set of proteins in KS cells,
      and which was augmented significantly in Dex-treated KS cells. Stimulation of KS
      cells with sIL-6R alpha/IL-6 or OM induced rapid tyrosine phosphorylation of the
      transcription factor STAT3, and Dex significantly enhanced the accumulation of
      tyrosine-phosphorylated STAT3. Electrophoretic mobility shift assays showed sIL
      6R alpha/IL-6- or OM-induced DNA-binding activity of STAT3 in KS cells, and Dex
      further increased this activity. Thus, Dex appears to participate in the gp130
      STAT3 signaling and transcriptional events by enhancing STAT3 activation, thereby
      leading to selective synergistic stimulation of KS cell growth with Dex and the
      gp130-related growth factors.

PMID- 9164977
TI  - Up-regulation of cytokine mRNA, adhesion molecule proteins, and MHC class II
      proteins in salivary glands of TGF-beta1 knockout mice: MHC class II is a factor
      in the pathogenesis of TGF-beta1 knockout mice.
AB  - Mice homozygous for a disrupted TGF-beta1 allele develop multiple
      lymphoproliferative disorders similar to those seen in the pseudolymphoma of
      Sjogren's syndrome. At 2 wk of age, these TGF-beta1 mutant mice begin to develop
      wasting syndrome and die at around 4 to 5 wk of age. We studied salivary glands
      from symptomatic mutant mice >14 days of age. Reverse transcriptase-PCR analysis
      showed up-regulation of proinflammatory cytokine genes such as IL-1alpha, IL
      1beta, IL-2, IL-4, IL-6, IL-10, and IFN-gamma in these mutant mice. Enhanced
      expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell
      adhesion molecule (VCAM-1), and MHC class II as well as CD4-positive T lymphocyte
      infiltration was detected by immunostaining. To elucidate the role of MHC class
      II, salivary glands from TGF-beta1/MHC class II double knockout mice were used to
      investigate the expression of adhesion molecules and MHC class II. In spite of
      the existence of basal intercellular adhesion molecule-1 expression on vessels,
      there was neither MHC class II expression, enhanced vascular cell adhesion
      molecule-1 expression, nor lymphocytic infiltration in the salivary glands. These
      results suggest that MHC class II plays a significant role in the pathogenesis of
      TGF-beta1 mutant mice. Although the mechanism that initiates multiple
      inflammatory diseases in these mice remains unclear, the context reported here
      would provide insight into the immunopathology of Sjogren's syndrome.

PMID- 9164978
TI  - Expression of IFN-inducible protein-10 in chronic hepatitis.
AB  - Chemokines such as IFN-inducible protein-10 (IP-10) and JE/monocyte chemotactic
      protein-1 (MCP-1) are induced in the murine liver in a tissue-specific manner. We
      examined whether IP-10 and MCP-1 are pathologically involved in chronic
      hepatitis. Whereas the serum levels of IP-10 and MCP-1 in patients with chronic
      persistent hepatitis C were elevated compared with those in normal volunteers,
      both chemokine levels were further significantly higher in patients with the
      active form (chronic active hepatitis (CAH)). The elevated IP-10 level was not a
      general phenomenon of inflammation, because it was not seen in patients with
      rheumatoid arthritis, whereas MCP-1 levels were elevated to the same extent in
      both patient groups. Better responsiveness to IFN therapy in CAH was related to
      lesser grades of necroinflammatory activity and was predicted by the lower IP-10
      and higher MCP-1 levels. IP-10 levels in patients cured by IFN therapy decreased
      to the levels in normal volunteers, while the MCP-1 levels only slightly
      decreased. Serum levels of both chemokines in patients who were not cured
      remained unchanged after IFN therapy. In situ hybridization analysis of CAH
      revealed that IP-10 mRNA was expressed mainly in hepatocytes around intralobular
      focal and periportal piecemeal necrosis, while some MCP-1 mRNA was expressed in
      some sinusoidal cells. These results suggested that IP-10 plays a specific role
      in the intralobular accumulation of mononuclear cells and/or the death of
      hepatocytes in chronic hepatitis.

PMID- 9164979
TI  - Intrinsic resistance to T cell infection with HIV type 1 induced by CD28
      costimulation.
AB  - When HIV-infected leukocytes are activated by the CD28 costimulatory receptor,
      HIV-1 is rapidly cleared from cultures, suggesting that costimulation can render
      T cells resistant to HIV-1 infection. In this study we tested the hypothesis that
      enhanced secretion of cytokines or chemokines could account for CD28-induced
      antiviral effects. In an acute infection system, resistance to infection with
      macrophage-tropic strains of HIV-1 was shown to be comprised of both soluble and
      cell-associated components. Induction of HIV-1 resistance was specific for CD28
      costimulation, in that a variety of other accessory receptors, such as CD2, CD4,
      CD5, and MHC class I, failed to confer the antiviral resistance. The soluble
      component was secreted by both CD4 and CD8 T cells, was not unique to CD28
      costimulation, and could be neutralized by removal of C-C chemokines (RANTES
      (regulated upon activation, normal T cell expressed and secreted) and macrophage
      inflammatory protein-1alpha and -1beta) from the culture supernatants of
      costimulated CD4 T cells. In contrast, CD28 stimulation of CD4 cells resulted in
      the specific induction of a pronounced intrinsic resistance to HIV-1 infection by
      macrophage tropic isolates of HIV-1.

PMID- 9164980
TI  - A pronounced thymic B cell deficiency in the spontaneously diabetic BB rat.
AB  - In an attempt to elucidate the origin of the T cell lymphopenia and/or the beta
      cell-specific autoimmunity observed in diabetes-prone Bio-Breeding (DP-BB) rats,
      a thymic cDNA library was subjected to differential screening with thymic cDNA
      probes of DP-BB rats and nonlymphopenic nondiabetic controls. This approach
      resulted in the identification of a prominent lack of thymic B cells in DP-BB
      rats. This deficiency is distinct from a less pronounced peripheral B cell
      deficiency of different timing. The thymic B cell defect is linked to the
      lymphopenia trait on chromosome 4 and thereby with susceptibility to diabetes in
      crosses involving the DP-BB rat. In conclusion, our data suggest that the
      contribution of thymic B cells to the (negative) selection of thymocytes is
      inadequate in DP-BB rats, thus providing a plausible explanation for at least
      some of the spontaneous autoimmune phenomena in this animal model.

PMID- 9164981
TI  - Reduced production of IL-12 and IL-12-dependent IFN-gamma release in patients
      with allergic asthma.
AB  - In atopic patients, allergen-specific T cells have acquired the Th2 phenotype,
      which is considered to be responsible for the class switch to IgE Ab formation.
      Because IL-12 is a key cytokine for the induction of Th1 responses, a reduced
      capacity to produce this cytokine could lead to aberrant Th2 development.
      Therefore, we examined the production of IL-12 in whole blood cultures from
      patients with allergic asthma (n = 15) in comparison with nonatopic control
      subjects (n = 15) to different stimuli. After stimulation with Staphylococcus
      aureus Cowan I strain (SAC) we observed a 2.6-fold reduction of IL-12 p70
      production in the patient group (p < 0.005). This was not due to a general
      failure of monocytes from these patients to produce cytokines, because the
      production of IL-6 was normal. SAC also induced the production of IFN-gamma,
      which was blocked by neutralization of IL-12. In line with the reduced levels of
      IL-12 secretion, the patient group showed a 3-fold reduction of IL-12-dependent
      IFN-gamma production (p < 0.005). The amounts of IL-12 and IFN-gamma were
      positively correlated in both the patient (R = 0.51 at 0.05% SAC and R = 0.64 at
      0.01% SAC) and the control groups (R = 0.64 at 0.05% SAC and R = 0.70 at 0.01%
      SAC). The IFN-gamma:IL-12 ratio was not different between patients and control
      subjects, indicating a normal response to IL-12. Diminished production of IL-12
      and IFN-gamma could not be explained by an increased production of IL-10, because
      in SAC-stimulated cultures IL-10 was hardly induced in both groups. Furthermore,
      after stimulation with Escherichia coli, the production of IL-10 was similar in
      patients and control subjects.

PMID- 9164982
TI  - Control of multiple autoantibodies linked with a lupus nephritis susceptibility
      locus in New Zealand black mice.
AB  - An NZB locus on distal chromosome 1 has been linked to murine lupus nephritis in
      backcross analyses of New Zealand mice. This locus, designated Nba2 for New
      Zealand Black autoimmunity 2, was found to colocalize in both (NZB x SM/J)F1 x
      NZW and (B6.H2z x NZB)F1 x NZB backcrosses, and was most likely situated between
      92 and 97 cM from the centromere. This region of mouse chromosome 1 encodes
      several candidate genes, including the low affinity Fc gamma receptor genes. Both
      backcrosses were examined by interval mapping for quantitative trait loci linked
      with autoantibody and total Ig production. Nba2 was linked with elevated serum
      levels of multiple autoantibodies, including a variety of antinuclear Abs (anti
      dsDNA, anti-chromatin and anti-histone) and autoantibodies to gp70, in both
      backcrosses. Nba2 was also linked (or showed a trend for linkage) with
      hypergammaglobulinemia and IgG1, IgG2a, and/or IgG3 levels in each backcross. In
      the (B6.H2z x NZB)F1 x NZB backcross, MHC was an additional genetic contribution
      that interacted with Nba2 in the production of autoantibodies and the development
      of nephritis. Together, these data provide new insight into the nature of one
      important genetic contribution to murine lupus and suggest that Nba2 may act as
      an immune response gene that influences Ag-driven B cell responses to self and
      possibly to exogenous Ags.

PMID- 9164983
TI  - Dietary fibers modulate indices of intestinal immune function in rats.
AB  - To explore the immunological roles of dietary fiber, male 4-wk-old Sprague-Dawley
      rats were fed for 2 wk cellulose (water-insoluble), konjak mannan (water
      soluble), pectin (water-soluble) or chitosan (acid-soluble) at 5 g/100 g diet.
      Serum IgE concentrations in rats fed konjak mannan, pectin and chitosan were
      significantly lower than in those fed cellulose (mean +/- SEM: 5.0 +/- 1.1, 3.6
      +/- 1.3, 3.0 +/- 1.2 and 9.6 +/- 1.9 microg/L, respectively). Rats fed pectin had
      significantly higher serum IgA and IgG concentrations (358 +/- 38 and 424 +/- 36
      mg/L for IgA and IgG, respectively) than those fed cellulose (240 +/- 31 and 337
      +/- 25 mg/L) or chitosan (176 +/- 22 and 379 +/- 23 mg/L), while the IgM
      concentration did not differ among the groups. Concentrations of IgA, IgG and IgM
      in mesenteric lymph node (MLN) lymphocytes generally were greater, while IgE
      concentration was lower, in rats fed pectin and chitosan than in those fed
      cellulose. The proportion of CD4+ T-cells in MLN lymphocytes was also dietary
      fiber-dependent, and the CD4+/CD8+ ratio was significantly higher in the pectin
      fed group than in all other groups. Under certain experimental conditions, MLN
      lymphocytes from rats fed pectin had markedly greater interferon-gamma
      concentration than cells from other groups, while the effect on tumor necrosis
      factor-alpha concentration was less marked. Thus, dietary fiber may have an
      immunoregulatory effect on the intestinal immune system of rats.

PMID- 9164984
TI  - Isoprenoids suppress the growth of murine B16 melanomas in vitro and in vivo.
AB  - Sundry mevalonate-derived constituents (isoprenoids) of fruits, vegetables and
      cereal grains suppress the growth of tumors. This study estimated the
      concentrations of structurally diverse isoprenoids required to inhibit the
      increase in a population of murine B16(F10) melanoma cells during a 48-h
      incubation by 50% (IC50 value). The IC50 values for d-limonene and perillyl
      alcohol, the monoterpenes in Phase I trials, were 450 and 250 micromol/L,
      respectively; related cyclic monoterpenes (perillaldehyde, carvacrol and thymol),
      an acyclic monoterpene (geraniol) and the end ring analog of beta-carotene (beta
      ionone) had IC50 values in the range of 120-150 micromol/L. The IC50 value
      estimated for farnesol, the side-chain analog of the tocotrienols (50 micromol/L)
      fell midway between that of alpha-tocotrienol (110 micromol/L) and those
      estimated for gamma- (20 micromol/L) and delta- (10 micromol/L) tocotrienol. A
      novel tocotrienol lacking methyl groups on the tocol ring proved to be extremely
      potent (IC50, 0.9 micromol/L). In the first of two diet studies, experimental
      diets were fed to weanling C57BL female mice for 10 d prior to and 28 d following
      the implantation of the aggressively growing and highly metastatic B16(F10)
      melanoma. The isomolar (116 micromol/kg diet) and the Vitamin E-equivalent (928
      micromol/kg diet) substitution of d-gamma-tocotrienol for dl-alpha-tocopherol in
      the AIN-76A diet produced 36 and 50% retardations, respectively, in tumor growth
      (P < 0.05). In the second study, melanomas were established before mice were fed
      experimental diets formulated with 2 mmol/kg d-gamma-tocotrienol, beta-ionone
      individually and in combination. Each treatment increased (P < 0.03) the duration
      of host survival. Our finding that the effects of individual isoprenoids were
      additive suggests the possibility that one component of the anticarcinogenic
      action of plant-based diets is the tumor growth-suppressive action of the diverse
      isoprenoid constituents of fruits, vegetables and cereal grains.

PMID- 9164985
TI  - Overexpression of cellular glutathione peroxidase does not affect expression of
      plasma glutathione peroxidase or phospholipid hydroperoxide glutathione
      peroxidase in mice offered diets adequate or deficient in selenium.
AB  - Selenium-dependent cellular glutathione peroxidase (GPX1) overexpressing
      [GPX1(+)] mice were derived by microinjecting a 5.3-kb cloned entire mouse GPX1
      genomic DNA into fertilized eggs. The objective of this study was to determine
      the effect of GPX1 overexpression and dietary selenium on the expression of
      selenoperoxidases and the status of lipid peroxidation of these transgenic
      animals. An experiment with a 2 x 2 factorial arrangement of treatments with 15
      GPX1(+) and 15 control mice (2 mo old) was conducted for 8 wk. Ten mice of each
      group (half males and females) were fed a Se-deficient, Torula yeast basal diet
      (0.02 mg Se/kg, no supplemental vitamin E) and five mice (three males and two
      females) were fed the basal diet supplemented with 0.51 mg Se/kg as Na2SeO3. The
      GPX1(+) mice had greater GPX1 activities (one- to sixfold, P < 0.0001) than the
      control mice at both levels of dietary selenium in all tissues except for liver,
      in which such difference (100%, P < 0.05) was observed only in Se-deficient mice.
      The GPX1 mRNA level in kidney and in lung of the Se-deficient GPX1(+) mice was
      81% and 7.5-fold greater (P < 0.003) than the respective control level.
      Overexpression of GPX1 did not alter phospholipid hydroperoxide glutathione
      peroxidase (GPX4) activities and mRNA levels or glutathione S-transferase (GST)
      activities in most of the tissues, plasma glutathione peroxidase (GPX3) activity
      or plasma Se concentrations. No differences in lipid peroxidation in kidney, lung
      or intestine were observed between the Se-deficient GPX1(+) and control mice. In
      conclusion, the overexpression of the GPX1 gene in these mice was tissue specific
      and did not affect the expression of GPX3, GPX4 or GST and plasma Se levels;
      dietary Se appeared to affect the GPX1 overexpression at its mRNA level.

PMID- 9164986
TI  - Dietary oxidized linoleic acid modifies lipid composition of rat liver microsomes
      and increases their fluidity.
AB  - The effect of dietary oxidized oil on the lipid composition, fluidity and
      function of rat liver microsomes was studied. Male growing rats were fed diets
      containing 10 g/100 g of a fresh (control) or oxidized (experimental) linoleic
      acid-rich preparation for 4 wk. High levels of fluorescent compounds and of
      thiobarbituric acid reactive substances indicated the occurrence of substantial
      lipid peroxidation in the microsomes of the experimental rats. The fluidity of
      the liver microsomes derived from rats fed the experimental diet was
      significantly higher than that of the membranes of the controls. This was due to
      profound differences in lipid composition of the liver microsomes, namely, a
      lower cholesterol to phospholipid molar ratio and a greater arachidonic acid
      content in the phospholipids of the rats fed the experimental diet. The fluidity
      differences were accompanied by greater activity of the microsomal enzymes,
      aldehyde dehydrogenase and NADPH cytochrome C reductase. The study demonstrated
      that ingestion of oxidized lipids caused profound alterations in membrane
      composition, fluidity and function. These alterations are likely to be associated
      with an enhanced cholesterol turnover, as indicated by the greater cholesterol
      excretion observed for the experimental rats.

PMID- 9164987
TI  - Lactase phlorizin hydrolase synthesis is decreased in protein-malnourished pigs.
AB  - We have examined the effect of protein malnutrition on brush border (BB) lactase
      phlorizin hydrolase (LPH) synthesis in young pigs. Two groups of four 3-wk-old
      pigs were fed diets containing either 19 g soy protein, 63 g carbohydrate and 5 g
      fat per 100 g diet (a protein-sufficient diet) or 3 g soy protein, 85 g
      carbohydrate and 5 g fat per 100 g diet (a protein-deficient diet). After 8 wk of
      consuming the diets, pigs were infused intravenously with 2H3-leucine for 8 h,
      then killed. The jejunum was collected for measurement of lactase activity, LPH
      mRNA abundance and the rate of LPH post-translational synthesis. Lactase
      activities did not differ between groups (mean 8.1 +/- 1.2 micromol x min(-1) x g
      mucosa(-1)). LPH mRNA abundance relative to elongation factor-1alpha mRNA (the
      constitutive/reference mRNA) was significantly (P < 0.05) higher in well
      nourished pigs (0.36 +/- 0.03%) than in protein-malnourished pigs (0.21 +/-
      0.02%). The rate constants of BB LPH post-translational synthesis were also
      significantly higher in the well-nourished (103 +/- 9% x d(-1)) than in the
      protein-malnourished pigs (66 +/- 8% x d(-1)). Further, the absolute synthesis
      rate of BB LPH, a measure of the amount of enzyme synthesized per gram of tissue,
      was significantly higher in well-nourished than in protein-malnourished pigs (in
      arbitrary units, 892 +/- 90 vs. 450 +/- 34, respectively). Thus, protein
      malnutrition affects both LPH mRNA abundance and post-translational processing in
      young pigs.

PMID- 9164988
TI  - Competitive reverse transcriptase-polymerase chain reaction shows that dietary
      zinc supplementation in humans increases monocyte metallothionein mRNA levels.
AB  - Zinc status is difficult to evaluate in humans. Metallothionein gene expression
      is transcriptionally regulated by dietary zinc and thus could serve as an
      assessment parameter based on zinc-dependent function. We used semiquantitative
      reverse transcriptase-polymerase chain reaction (RT-PCR) to establish that MT
      mRNA is increased in a human monocytic cell line by addition of zinc to the
      medium. To examine this response in human subjects, a dietary supplement of 50 mg
      zinc gluconate/d was given for 15 d. Monocytes were purified from venous blood
      using NycoPrep 1.068. Monocyte purity was determined by flow cytometry using
      fluorescent anti-human monocyte CD14 antibodies. Total monocyte RNA was extracted
      and converted to cDNA by reverse transcription. Competitive RT-PCR was used to
      analyze differences between cDNA levels that are proportional to MT mRNA levels
      in monocytes from zinc-supplemented and control subjects. RT-PCR oligonucleotide
      primers were designed to amplify both a 201 bp segment of the human MT cDNA and a
      180 bp competitor cDNA template. The 180 bp competitor cDNA template was used for
      MT cDNA quantitation. The RT-PCR data show that there was a significant increase
      in monocyte MT mRNA in subjects within 6 d of zinc supplementation, which
      remained elevated at d 15 of supplementation. In contrast, plasma zinc was
      greater at d 6 of zinc supplementation, but by d 15 of supplementation, while
      still elevated, was close to control levels. These data suggest that monocyte MT
      mRNA levels respond to zinc supplementation and that the response could serve as
      a more useful assessment variable than plasma zinc for the measurement of zinc
      status in humans.

PMID- 9164989
TI  - Questionnaire-based measures are valid for the identification of rural households
      with hunger and food insecurity.
AB  - This study assessed the validity of questionnaire-based measures for the
      identification of rural households with hunger and food insecurity. Data used
      were from a 1993 survey of 193 households with women and children living at home
      in a rural county. Two interviews provided data on demographics, factors
      contributing to food insecurity, coping strategies, fruit and vegetable
      consumption, disordered eating behaviors, height, weight, dietary recall and
      household food-stores inventory. This information was used to develop a
      definitive criterion measure for hunger and food insecurity to compare with
      hunger and food insecurity items from Radimer/Cornell, the Community Childhood
      Hunger Identification Project (CCHIP) and the Third National Health and Nutrition
      Examination Survey (NHANES III). The Radimer/Cornell and CCHIP questionnaire
      based measures had good specificity (i.e., percentage of truly food secure
      correctly classified; 63-71%) and excellent sensitivity (i.e., percentage of
      truly food insecure correctly classified; 84-89%) when compared with the
      criterion measure. Estimates of the prevalence of household food insecurity from
      the criterion, Radimer/Cornell and CCHIP measures were almost identical. The
      overall agreement of the Radimer/Cornell and CCHIP measures was very good. These
      measures can be validly used to screen for hunger and food insecurity among rural
      households similar to those studied and to target subpopulations for food
      programs. The NHANES III item alone had excellent specificity but poor
      sensitivity, and underestimated prevalence.

PMID- 9164990
TI  - A diet rich in fat and poor in dietary fiber increases the in vitro formation of
      reactive oxygen species in human feces.
AB  - Production of reactive oxygen species in the lumen of the colon, a process that
      is influenced by nutritional factors, may be important in the etiology of
      colorectal cancer. Because research on humans in support of this hypothesis is
      lacking, the objective of this study was to measure the effect of different
      dietary compositions on the in vitro oxygen radical production in human feces.
      Over a period of 12 d, seven healthy subjects received a diet rich in fat (50%)
      and meat and poor in dietary fiber. After a period of 1 wk, they received a
      vegetarian diet poor in fat (20%) and rich in dietary fiber. At the end of each
      study period, feces were collected and analyzed for in vitro oxygen radical
      production with dimethylsulfoxide as the free radical scavenger. The mean
      hydroxyl radical production was 13 times greater in feces of subjects when they
      consumed the diet rich in fat and poor in dietary fiber [52.7 +/- 29.5
      micromol/(g feces x h)] than when they consumed the diet poor in fat and rich in
      dietary fiber [3.9 +/- 3.9 micromol/(g feces x h); P < 0.05]. This difference was
      associated with a 42% higher fecal iron concentration when they consumed the
      first diet (7.0 +/- 19.2 micromol/g feces) than when they consumed the second
      (4.9 +/- 1.9 micromol/g feces; P < 0.05). The results of this study confirm that
      diets high in fat and meat and low in fiber markedly increase the potential for
      hydroxyl radical formation in the feces, which in turn may contribute to an
      enhanced risk of colorectal cancer.

PMID- 9164991
TI  - Biotin status assessed longitudinally in pregnant women.
AB  - This study assessed biotin nutritional status longitudinally during pregnancy as
      judged by urinary excretion of biotin and biotin metabolites and by serum
      concentration of biotin. 3-Hydroxyisovaleric acid excretion was also assessed
      because increased excretion of that acid reflects decreased tissue activity of
      the biotin-dependent enzyme, methylcrotonyl-CoA carboxylase. Thirteen women
      provided untimed urine samples during both early and late pregnancy. Twelve
      nonpregnant women served as controls. Biotin and metabolites were determined by a
      combined HPLC/avidin-binding assay. 3-Hydroxyisovaleric acid was determined by
      gas chromatography/mass spectrophotometry. Significance of changes from early to
      late pregnancy was tested by paired t test; to compare nonpregnant controls with
      early and late pregnancy, ANOVA was used. During early pregnancy, biotin
      excretion was not significantly different than controls; however, 3
      hydroxyisovaleric acid excretion was significantly increased relative to controls
      (P < 0.0001) and was greater than the upper limit of normal in 9 of 13 women.
      From early to late pregnancy, biotin excretion decreased in 10 of 13 women (P <
      0.01); by late pregnancy, biotin excretion was less than normal in six women.
      During late pregnancy, 3-hydroxyisovaleric acid remained significantly increased
      relative to controls (P < 0.0001). Serum concentrations of biotin were
      significantly greater than those of controls during early pregnancy (P < 0.0001)
      and decreased in each woman from early to late pregnancy (P < 0.0001). These data
      provide evidence that biotin status decreases during pregnancy.

PMID- 9164992
TI  - Acarbose enhances human colonic butyrate production.
AB  - Earlier studies suggest that butyrate has colonic differentiating and nutritional
      effects and that acarbose increases butyrate production. To determine the effects
      of acarbose on colonic fermentation, subjects were given 50-200 mg acarbose or
      placebo (cornstarch), three times per day, with meals in a double-blind crossover
      study. Fecal concentrations of starch and starch-fermenting bacteria were
      measured and fecal fermentation products determined after incubation of fecal
      suspensions with and without added substrate for 6 and 24 h. Substrate additions
      were cornstarch, cornstarch plus acarbose and potato starch. Dietary starch
      consumption was similar during acarbose and placebo treatment periods, but fecal
      starch concentrations were found to be significantly greater with acarbose
      treatment. Ratios of starch-fermenting to total anaerobic bacteria were also
      significantly greater with acarbose treatment. Butyrate in feces, measured either
      as concentration or as percentage of total short-chain fatty acids, was
      significantly greater with acarbose treatment than with placebo treatment.
      Butyrate ranged from 22.3 to 27.5 mol/100 mol for the 50-200 mg, three times per
      day doses of acarbose compared with 18.3-19.3 mol/100 mol for the comparable
      placebo periods. The propionate in fecal total short-chain fatty acids was
      significantly less with acarbose treatment (10.7-12.1 mol/100 mol) than with
      placebo treatment (13.7-14.2 mol/100 mol). Butyrate production was significantly
      greater in fermentations in samples collected during acarbose treatment, whereas
      production of acetate and propionate was significantly less. Fermentation
      decreased when acarbose was added directly to cornstarch fermentations. Acarbose
      effectively augmented colonic butyrate production by several mechanisms; it
      reduced starch absorption, expanded concentrations of starch-fermenting and
      butyrate-producing bacteria and inhibited starch use by acetate- and propionate
      producing bacteria.

PMID- 9164993
TI  - Small changes of dietary (n-6) and (n-3)/fatty acid content ration alter
      phosphatidylethanolamine and phosphatidylcholine fatty acid composition during
      development of neuronal and glial cells in rats.
AB  - It has been suggested that the fat composition of infant formula should provide
      arachidonic acid [20:4(n-6)] and docosahexaenoic acid [22:6(n-3)] or increased
      alpha-linolenic acid [18:3(n-3)] to optimize the (n-3) and (n-6) fatty acid
      content of brain during infant development. This experiment examined the effects
      of feeding increased levels of 18:3(n-3), 20:4(n-6) and 22:6(n-3) on brain
      development in neonatal rats. Diets varying in (n-6) and (n-3) fatty acid content
      with or without 20:4(n-6) or 22:6(n-3), at levels proposed for infant formula,
      were fed to nursing dams from parturition and subsequently to weaned pups until 6
      wk of age. Neuronal and glial cells were isolated from the frontal region,
      cerebellum and hippocampus of the brain. Fatty acid analyses of ethanolamine- and
      choline-phosphoglycerides indicated that small changes in the dietary (n-6)/(n-3)
      ratio significantly altered neuronal and glial membrane fatty acid composition.
      Brain regions and cell types varied in amount and rate of 20:4(n-6) and 22:6(n-3)
      accretion. Fatty acid composition of individual phosphoglycerides was distinct
      and exhibited changes with age. Inclusion of both 20:4(n-6) and 22:6(n-3) in the
      diet resulted in alteration of brain fatty acid composition reflecting the fatty
      acid composition of the diet. If analogous developmental changes occur in human
      brain, then these results imply that addition of 20:4(n-6) and 22:6(n-3) or a
      reduced 18:2(n-6):18:3(n-3) ratio in infant formula may result in fatty acid
      profiles of neuronal and glial cells in formula-fed infants similar to those
      observed in breast-fed infants.

PMID- 9164994
TI  - Glucocorticoids play an important role in mediating the enhanced metabolism of
      arginine and glutamine in enterocytes of postweaning pigs.
AB  - Weaning is associated with increased intestinal metabolism of glutamine and
      arginine as well as elevated plasma concentrations of cortisol (the major
      circulating glucocorticoid) in pigs. The objective of this study was to determine
      if cortisol plays an important role in mediating the enhanced amino acid
      metabolism in enterocytes of weaned pigs by administering RU486 (a glucocorticoid
      receptor antagonist). Eighteen 21-d-old pigs were randomly assigned to three
      groups of six. Two of these groups received intramuscular injections of 0 or 10
      mg RU486 per kg body weight 5 min before and 24 and 72 h after weaning to a corn
      soybean meal-based diet. The third group was allowed to suckle freely from sows.
      When the pigs were 29 d old, jugular venous blood was obtained and pigs were
      killed for preparation of jejunal enterocytes. The activities of arginase,
      argininosuccinate synthase (ASS), argininosuccinate lyase (ASL) and pyrroline-5
      carboxylate (P5C) synthase were measured. For metabolic studies, cells were
      incubated for 0 or 30 min at 37 degrees C in 2 mL of Krebs-bicarbonate buffer (pH
      7.4) containing 0 or 2 mmol/L L-[U-14C]arginine or 2 mmol/L L-[U-14C]glutamine.
      In comparison with suckling pigs, weaning resulted in increases in the following:
      1) the activities of arginase, ASS, ASL and P5C synthase, 2) the metabolism of
      arginine to CO2, proline and ornithine, and 3) the conversion of glutamine to
      ornithine, citrulline and CO2. The effects of the administration of RU486 were as
      follows: 1) attenuation of the increase in arginase activity and the production
      of ornithine from arginine, 2) abolition of the induction of ASL and P5C
      synthase, and 3) prevention of the increase in glutamine metabolism and the
      production of proline and CO2 from arginine in enterocytes of weaned pigs. These
      data suggest that glucocorticoids play an essential role in mediating the
      enhanced intestinal degradation of arginine and glutamine during weaning.

PMID- 9164995
TI  - Dietary protein and amino acid levels alter threonine dehydrogenase activity in
      hepatic mitochondria of Gallus domesticus.
AB  - Experiments were conducted to determine if hepatic threonine dehydrogenase (TDH)
      activity is influenced by dietary protein or specific amino acid concentrations.
      In an initial experiment, young chicks were deprived of feed for 60 h or had
      access for 72 h to a 22% protein basal diet, a protein-free diet or a 51% high
      protein diet. TDH activity was determined as aminoacetone and glycine
      accumulation during incubation of liver mitochondria. TDH activity was
      significantly (P < 0.01) lower in chicks fed the protein-free diet and
      significantly greater in chicks fed the high protein diet compared with chicks
      fed the basal diet. Food deprivation had no effect on TDH activity. A second
      experiment was conducted using the 22 and 51% protein diets, the 22% protein diet
      plus 1.14 g/100 g diet threonine (equivalent to the free plus protein-bound
      threonine content of the high protein diet), and the 51% protein diet containing
      0.15 g/100 g diet less threonine. TDH was increased in chicks fed either high
      protein diet (P < 0.05). There were no significant differences in TDH activity,
      however, between chicks fed the basal diet and the threonine-supplemented diet or
      between chicks fed the two high protein diets. In two other experiments, the
      activity of TDH was investigated in chicks fed for 9 d dietary supplements of
      either serine or glycine (5.5 or 4 g/100 g basal diet, respectively). The
      supplements were added to the basal diet or the basal diet imbalanced by the
      addition of 6% branched-chain amino acids. Neither the serine nor the glycine
      supplement significantly altered TDH activity or the increased activity
      associated with a branched-chain amino acid-induced threonine imbalance. The
      results suggest that hepatic TDH activity is influenced by protein level or other
      amino acids more than by threonine itself.

PMID- 9164996
TI  - A chick bioassay approach for determining the bioavailable choline concentration
      in normal and overheated soybean meal, canola meal and peanut meal.
AB  - Our objectives were to use a soy protein isolate (SPI) diet containing 2-amino-2
      methyl-1-propanol, an inhibitor of choline biosynthesis, to determine the
      bioavailable choline content of normal and overheated soybean meal (SBM), canola
      meal (CM) and peanut meal (PM). In the first four experiments, it was determined
      that weight gain of chicks fed the basal diet would respond linearly (P < 0.05)
      to graded levels of crystalline choline and would not respond to betaine, and
      that when fortified with adequate choline, no weight gain or feed intake response
      would occur upon addition of 100 g/kg SBM, CM or PM to the basal diet.
      Furthermore, addition of crystalline amino acids simulating the amino acid
      composition of 100 g/kg SBM did not alter the utilization of crystalline choline.
      In Experiment 5, feeding graded doses of choline, SBM, CM or PM resulted in
      linear (P < 0.05) increases in weight gain. Multiple linear regression analysis
      indicated bioavailable choline concentrations of 1708, 1545 and 1203 mg/kg for
      SBM, CM and PM, respectively. In Experiment 6, no differences (P > 0.05) in
      bioavailable choline concentrations occurred between normal and overheated SBM,
      CM or PM, and the bioavailable choline concentration of normal SBM, CM and PM was
      2002, 1464 and 1320 mg/kg, respectively. Average bioavailable choline levels were
      83, 24 and 76% of analytically determined choline levels in SBM, CM and PM,
      respectively. Canola meal, although three times as rich in total choline as SBM,
      has less bioavailable choline than SBM. A substantial portion of choline in SBM,
      CM and PM is unavailable, and overheating does not appear to decrease the
      bioavailability of choline in these products.

PMID- 9164997
TI  - Desaturation of stearate is insufficient to increase the concentrations of oleate
      in cultured rat hepatocytes.
AB  - Desaturation of stearate and palmitate and its effect on cellular accumulation of
      oleate were determined in primary culture of rat hepatocytes. The rate of oleate
      synthesis as measured by the formation of monounsaturated fatty acids from
      stearate was significantly higher than that from palmitate. The rate of [1
      (14)C]stearate incorporation into oleate [1208 +/- 195 pmol/(mg protein x 4 h)]
      was 80% higher than that of [1-(14)C]palmitate [(672 +/- 82 pmol/(mg protein x 4
      h)]. Despite the different rates of desaturation, the cellular oleate
      concentrations did not differ in the cells treated with stearate and palmitate
      (i.e., 42.5 +/- 4.5 vs. 40.8 +/- 5.2 nmol/mg protein). On the other hand, oleate
      concentration in the cells incubated with exogenous oleate was 198.1 +/- 9.5
      nmol/mg protein. There was a dose-dependent increase in cellular stearate
      concentration by increasing stearate concentrations from 0.5 mmol/L to 4.0 mmol/L
      in culture medium. A linear increase in cellular stearate concentration was also
      achieved by increasing the duration of incubation with 1.0 mmol/L stearate from 2
      to 24 h. Despite the marked increases in stearate concentrations under these
      conditions, oleate concentrations remained unchanged in the cells. These results
      do not support the contention that the hypocholesterolemic effect of stearate may
      be mediated by its conversion to oleate, although stearate is a more favorable
      substrate for desaturation than palmitate.

PMID- 9164998
TI  - The protein digestibility-corrected amino acid score method overestimates quality
      of proteins containing antinutritional factors and of poorly digestible proteins
      supplemented with limiting amino acids in rats.
AB  - The validity of the protein digestibility-corrected amino acid score (PDCAAS)
      method in predicting the quality of fourteen protein products was compared with
      the commonly used protein quality methods, protein efficiency ratio (RER) and net
      protein ratio (NPR). A rat growth and balance study was conducted to determine
      protein digestibility and quality of the animal and vegetable protein products by
      the PER and NPR methods. Amino acid compositions of the products were also
      determined, and PDCAAS were calculated using a rat and a human pattern of amino
      acid requirements. Compared to the biological methods, the scoring method
      overestimated protein quality of mustard flour [PDCAAS of 84-92% vs. relative PER
      (RPER) or relative NPR (RNPR) of 0], raw black beans (PDCAAS of 45-72% vs. RPER
      or RNPR of 0), alkaline-treated lactalbumin and soybean protein isolate (PDCAAS
      of 44-67% vs. RPER or RNPR of 0) and heated skim milk (PDCAAS of 29-31% vs. RPER
      and RNPR of 0-5%). The scoring method also overestimated the protein quality of
      zein (true protein digestibility of 63%) supplemented with Lys, Met, Thr and Trp
      (PDCAAS of 63-71% vs. RPER and RNPR of 3-44%). These data demonstrate that the
      PDCAAS method is inappropriate for predicting protein quality of those protein
      sources which may contain naturally occurring growth-depressing factors or
      antinutritional factors formed during alkaline and/or heat processing.

PMID- 9164999
TI  - Analgesic response to stress is reduced in perinatally undernourished rats.
AB  - Stress-induced analgesia was evaluated in adult rats submitted early in life to a
      protein deprivation schedule. Rats were undernourished with a hypoproteic diet
      containing 80 g casein/kg diet from d 14 of gestation until 50 days of age. Rats
      were thereafter fed a balanced nonpurified diet until 140 days of age, when they
      were exposed to two stressors: forced swimming and acute restraint, after which
      the analgesic response was evaluated. In addition, the analgesic response induced
      by different morphine doses was determined in another group of rats. Basal
      latency was not different in deprived and control rats. Undernourished rats
      presented a significantly lower analgesic response in both stress situations.
      However, when the analgesic response induced by different morphine doses (1, 2, 4
      and 8 mg/kg, s.c.) was assessed, a significantly higher response occurred in
      undernourished rats compared to control rats. This lower stress-induced analgesia
      in undernourished rats may account for the behavioral alterations attributed to
      early undernutrition.

PMID- 9165000
TI  - Vitamin A deficiency exacerbates methotrexate-induced jejunal injury in rats.
AB  - Two studies were conducted to investigate whether vitamin A-deficient rats were
      more susceptible to intestinal injury caused by methotrexate (MTX), since vitamin
      A deficiency alone causes only mild changes to jejunal structure and function.
      Weanling male rats were fed a vitamin A-deficient diet (-VA) for 40-42 d and
      compared to rats either pair-fed (PF) or with free access (+VA) to the same diet.
      Drinking water of PF and +VA rats was supplemented with 37.5 microg (Study 1) or
      75 microg (Study 2) vitamin A (Rovimix A 500W)/d. Rats in each group received MTX
      (-VAMTX, PFMTX, +VAMTX) or vehicle. MTX administration reduced intestinal mucosal
      wet weight, protein and DNA concentrations, and sucrase and maltase activities in
      -VA and PF rats (P < 0.02). In Study 1, -VAMTX rats developed a severe jejunal
      enteropathy and had a higher incidence of diarrhea (P < 0.005), greater weight
      loss (P < 0.005), more disruption of villus architecture (P < 0.0001) and lower
      disaccharidase activity (P < 0.007) than PFMTX rats. Similar results were
      observed in Study 2. Liver retinol concentration (but no other variable) was
      greater in rats receiving 75 microg vitamin A/d (P < 0.001) than in those
      receiving 37.5 microg/d. The interaction of vitamin A deficiency and small
      intestinal injury may explain the efficacy of vitamin A supplementation in
      preventing childhood diarrheal disease mortality in developing countries, and
      highlights the need for ensuring adequate vitamin A status in people worldwide
      with diseases and/or treatments which may injure the gastrointestinal tract.

PMID- 9165001
TI  - Small changes in essential amino acid concentrations alter diet selection in
      amino acid-deficient rats.
AB  - The rat's sensitivity to changes in the dietary limiting amino acid concentration
      (LAA) was examined on the basis of dietary selection. Rats were adapted to
      purified low protein basal (Basal) diets in which threonine (Thr) was the LAA
      (0.188-0.212% wt/wt of diet). In Experiment 1, rats made a clear selection for
      their adaptation diet over a diet containing 0.012% less threonine after 2-3 d of
      choice. Rats made no clear dietary selection when given a choice between their
      adaptation diet and a diet containing 0.012% more threonine. Experiment 2 was
      conducted to examine the rat's sensitivity to small decreases in the LAA
      concentration. Rats adapted to a 0.200% Thr-Basal diet clearly responded to
      decreases as small as 0.009% in the concentration of threonine and selected
      against the more deficient diet when given a choice between it and the 0.200% Thr
      Basal adaptation diet. Because plasma and brain amino acid concentrations are
      important for detection of other amino acid deficiencies, these variables were
      measured to determine whether they were affected by such small changes in dietary
      amino acid concentration. In Experiments 3 and 4, rats were adapted to the 0.200%
      Thr-Basal diet and then fed 0.188, 0.200 or 0.212% Thr-Basal diets for 6 h, or
      0.188 and 0.212% Thr-Basal for 54 h. Amino acid concentrations in plasma,
      prepiriform cortex and anterior cingulate cortex were not significantly different
      among treatments. Norepinephrine concentration in the prepiriform cortex was not
      affected by dietary treatment. We conclude that small decreases in LAA
      concentration can cause selection against the more deficient diet, but that
      detection of such deficiencies does not require significant changes in plasma and
      brain amino acid concentrations.

PMID- 9165002
TI  - Food supplementation during lactation shortens anestrus and elevates
      gonadotropins in rats.
AB  - Breastfeeding delays the resumption of ovulation in women, a phenomenon
      particularly important in less developed areas. Although human and animal studies
      indicate that undernutrition extends the period of lactational anestrus, the
      effect of improving nutritional status during lactation on this time of
      infecundability, however, is less clear. To assess the effects of food
      supplementation on duration of lactational anestrus, Sprague-Dawley rats were
      assigned to one of three dietary groups: 1) control (C), given unrestricted
      access to diet AIN-76A; 2) food-restricted (FR), fed 50% of the control intake;
      and 3) food-supplemented (FS), food-restricted until d 0 of lactation and
      thereafter given unrestricted access to diet AIN-76A. Time to first detectable
      proestrus was monitored starting on d 10 of lactation. Nursing behaviors and
      gonadotropin and prolactin concentrations were measured in both intact and
      ovariectomized dams on d 10, 15 and 20 of lactation; we report these data only on
      the ovariectomized group, which represents the more appropriate animal model of
      human reproductive physiology during lactation. Proestrus returned significantly
      (P < 0.0001) sooner in both FS (18.1 +/- 2.4 d) and C (18.0 +/- 2.9 d) than in FR
      (28.8 +/- 2.8 d) intact dams. FS rats had higher luteinizing hormone and follicle
      stimulating hormone concentrations than FR rats (P < 0.0001 for each). Prolactin
      concentrations were lower on d 20 than on d 10 of lactation for all groups (P <
      0.02), but we found no effect of dietary treatment. FS rats spent more time away
      from their pups (P < 0.05) and experienced less suckling (P < 0.05) than FR rats
      on d 15 of lactation. These results indicate that food supplementation of
      previously underfed rats hastens the return of ovulation and is accompanied by
      alterations in nursing behaviors.

PMID- 9165003
TI  - The path less traveled by.

PMID- 9165004
TI  - Growth factor-induced transcription via the serum response element is inhibited
      by cyclic adenosine 3',5'-monophosphate in MCF-7 breast cancer cells.
AB  - The effect of increased intracellular cAMP on MCF-7 breast cancer cell growth was
      examined by treating cells with either forskolin, an activator of adenylate
      cyclase, or 8-[4-chlorophenylthio]-cAMP (8-CPT-cAMP), a cAMP analog. Compared to
      cells maintained in control medium, treatment with either 1 or 10 microM
      forskolin decreased cell growth by 17% and 68%, respectively, whereas treatment
      with 250 microM 8-CPT-cAMP decreased cell growth by 29%. To determine whether
      this effect of cAMP on cell growth was mediated by inhibition of the activity of
      extracellular signal-regulated kinases 1 and 2 (ERK1 and -2), two mitogen
      activated protein kinases, the effect of cAMP on growth factor-induced ERK
      activity in MCF-7 cells was examined. Treatment with either insulin-like growth
      factor I (IGF-I) or epidermal growth factor (EGF) for 10 min stimulated a 4- to 8
      fold increase in ERK1 and -2 activity. This effect of IGF-I and EGF was not
      inhibited by increased intracellular cAMP generated by pretreatment of the cells
      with 10 microM forskolin. Similarly, 10 microM forskolin had no effect on IGF-I-
      or EGF-induced ERK activity in cells treated with growth factor for 30 min. To
      determine whether cAMP inhibits other growth factor-mediated effects, its effect
      on the activity of the serum response element (SRE), a DNA promoter element whose
      activity is regulated by a variety of growth-promoting events, was examined. For
      these assays, MCF-7 cells were transiently transfected with pTK81-SRE-Luc, a
      luciferase fusion gene that contains the SRE cloned 5' to a minimal thymidine
      kinase promoter and the luciferase gene. Treatment with either IGF-I or EGF
      increased pTK81-SRE-Luc activity in a dose-dependent fashion. Pretreatment of
      cells with 10 microM forskolin decreased IGF-I- and EGF-stimulated luciferase
      activity by approximately 75%. An intermediate effect was observed using 1 microM
      forskolin. When intracellular cAMP levels were increased using 8-CPT-cAMP,
      similar results were obtained. SRE activity is dependent upon the activation by
      phosphorylation of a ternary complex factor; included among the ternary complex
      factors is Elk-1. When MCF-7 cells were cotransfected with a vector that
      expresses a Gal4/Elk-1 fusion protein and UAS-TK-Luc, a plasmid that contains two
      Gal4 DNA recognition sites cloned 5' to a thymidine kinase promoter and the
      luciferase gene, treatment with forskolin partially inhibited the activation of
      Elk-1 by IGF-I and EGF. These data demonstrate that in MCF-7 breast cancer cells,
      cAMP has no effect on IGF-I- or EGF-induced ERK activity, but it inhibits growth
      factor-induced transcription. Taken together with the effects of cAMP on IGF-I-
      and EGF-induced Elk-1 activation, these data suggest that the effect of cAMP on
      SRE activity occurs distal to ERK activation, possibly via inhibition of an ERK
      independent pathway. Finally, these data indicate that the effect of increased
      intracellular cAMP on breast cancer growth may be mediated through inhibition of
      specific growth factor-induced effects, including gene transcription.

PMID- 9165005
TI  - Regulation by thyroid-stimulating hormone of sodium/iodide symporter gene
      expression and protein levels in FRTL-5 cells.
AB  - To investigate the mechanism of I- transport stimulation by TSH, we studied the
      effects of TSH on Na+/I- symporter (NIS) messenger RNA (mRNA) and protein levels
      in FRTL-5 cells and correlated these with I- transport activity. When 1 mU/ml TSH
      was added to quiescent FRTL-5 cells, a 12-h latency was observed before the onset
      of increased I- transport activity, which reached a maximum [approximately 27
      times basal (5H medium) levels] at 72 h. In contrast, Northern blot analysis,
      using rat NIS complementary DNA as a probe, revealed that addition of TSH to
      these cells significantly increased NIS mRNA at 3-6 h, reaching a maximum after
      24 h (approximately 5.9 times basal levels). Forskolin and (Bu)2cAMP mimicked
      this stimulatory effect on both the I- transport activity and mRNA levels. D
      ribofranosylbenzimidazole, a transcription inhibitor, almost completely blocked
      TSH-induced stimulation of I- transport and NIS mRNA levels. Western blot
      analysis demonstrated that TSH increased NIS protein levels at 36 h, reaching a
      maximum at 72 h, in parallel with the kinetics of TSH-induced I- transport
      activity. However, it also showed that the amount of NIS protein already present
      in FRTL-5 cell membranes before the addition of TSH was about one third of the
      maximum level induced by TSH. These results indicate that stimulation of I-
      transport activity by TSH in thyrocytes is partly due to a rapid increase in NIS
      gene expression, followed by a relatively slow NIS protein synthesis. However,
      the existence of an abundant amount of protein in quiescent FRTL-5 cells with
      very low I- transport activity also suggests that this activity is controlled by
      another TSH-regulated factor(s).

PMID- 9165006
TI  - Mouse vitamin D-24-hydroxylase: molecular cloning, tissue distribution, and
      transcriptional regulation by 1alpha,25-dihydroxyvitamin D3.
AB  - Vitamin D-24-hydroxylase (24-OHase) is a cytochrome P-450 enzyme that catalyzes
      the conversion of 25-hydroxyvitamin D3 (25OHD3) and 1alpha,25-dihydroxyvitamin D3
      [1,25-(OH)2D3] to 24,25-dihydroxyvitamin D3 and 1,24,25-trihydroxyvitamin D3,
      respectively. A full-length complementary DNA for mouse 24-OHase has now been
      characterized. The complementary DNA consists of 3309 bp and encodes a protein of
      514 amino acids that shows 82% and 95% sequence identity with the human and rat
      enzymes, respectively. Northern blot analysis of tissues from mice injected with
      1,25-(OH)2D3 (24 pmol/g) revealed that the 3.4-kb 24-OHase messenger RNA (mRNA)
      is most abundant in kidney and intestine, with smaller amounts present in skin,
      thymus, and bone. RT-PCR and Southern blot analysis detected 24-OHase mRNA in
      several other tissues including lung, testis, spleen, pancreas, and heart.
      Intraperitoneal injection of 1,25-(OH)2D3 induced dose- and time-dependent
      increases in both 24-OHase mRNA abundance and enzyme activity in mouse kidney.
      Similarly, 1,25-(OH)2D3-induced increases in both 24-OHase mRNA and activity were
      apparent in the duodenum. Although 1,25-(OH)2D3 increased the amount of 24-OHase
      mRNA in skin, enzyme activity was not detected in this tissue. Pretreatment of
      mice with cycloheximide (400 microg/g), an inhibitor of protein synthesis,
      potentiated the increase in 24-OHase mRNA abundance, but blocked the increase in
      24-OHase activity, induced by 1,25-(OH)2D3 in kidney and duodenum, suggesting
      that 24-OHase gene expression may be regulated not only by the vitamin D receptor
      but also by a short-lived repressor protein.

PMID- 9165007
TI  - 1,25-dihydroxyvitamin D3 stimulates the assembly of adherens junctions in
      keratinocytes: involvement of protein kinase C.
AB  - Signaling via intercellular junctions plays an important role in the regulation
      of growth and differentiation of epithelial cells. Loss of cell-cell contacts has
      been implicated in carcinogenesis, tumor progression, and metastasis. Here, we
      investigated whether 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] was able to
      stimulate the assembly of adherens junctions and/or desmosomes in cultured human
      keratinocytes. After 4-day incubation, 1,25-(OH)2D3 caused assembly of adherens
      junctions, but not desmosomes. The adherens junctions were identified upon known
      ultrastructural criteria and evidence of the translocation of specific junctional
      proteins (E-cadherin, P-cadherin, alpha-catenin, and vinculin) to the cell-cell
      borders. The presence of alpha-catenin and vinculin at cell-cell borders
      indicated that the adherens junctions were functional. This was further supported
      by showing that anti E-cadherin antibody inhibited the 1,25-(OH)2D3-induced
      keratinocyte stratification. A relation between protein kinase C and adherens
      junction regulation was noticed. 1,25-(OH)2D3-dependent formation of junctions
      was blocked by the inhibitors of protein kinase C, bisindolylmaleimide and 1-(5
      isoquinolinylsulfonyl)-2-methyl-piperazine (H-7), and treatment of keratinocytes
      with 1,25-(OH)2D3 caused a rapid activation of protein kinase C and its
      translocation to the membranes. Formation of intercellular contacts may be an
      important mechanism of 1,25-(OH)2D3 action in hyperproliferative and neoplastic
      diseases.

PMID- 9165008
TI  - Luteinizing hormone secretion and corticotropin-releasing factor gene expression
      in the paraventricular nucleus of rhesus monkeys following cortisol synthesis
      inhibition.
AB  - Corticotropin-releasing Factor (CRF) is an important inhibitory neuromodulator of
      GnRH/LH secretion, and mediates in part the inhibitory effects of stress on the
      hypothalamic-pituitary-gonadal axis. The purpose of the present study was to
      further investigate CRF's role in regulating LH secretion in primates. This was
      accomplished by examining LH secretion in ovariectomized rhesus monkeys (n = 7)
      following cortisol synthesis inhibition with metyrapone. Infusion of metyrapone
      (5 mg/kg per h) for 4 h decreased cortisol levels to less than 20% of controls
      while increasing ACTH approximately 10-fold. LH concentrations were not affected
      by this acute activation of the hypothalamic-corticotroph axis. In a second
      experiment, metyrapone was infused for 10 h before collecting serial blood
      samples every 15 min for 6 h. Although this protocol produced a sustained
      increase in ACTH, no apparent effect on pulsatile LH secretion compared with
      saline controls was observed. Mean LH (+/- SEM) levels calculated for consecutive
      2-h increments were 87.6 +/- 9.2 (0-2 h) 82.1 +/- 5.5 (2-4 h), and 80.7 +/- 4.8
      (4-6 h) ng/ml in saline pretreated animals compared with 83.6 +/- 4.9, 79.8 +/-
      5.8, and 72.5 +/- 6.2 ng/ml, respectively, in metyrapone pretreated monkeys. The
      same regimen of metyrapone infusion increased CRF messenger RNA levels in the
      paraventricular nucleus by approximately 33% (P < 0.0002). In a final experiment
      designed to examine the potential synergy between CRF and cortisol, the LH
      response to insulin-induced hypoglycemia was contrasted in saline and metyrapone
      pretreated monkeys. LH concentrations were reduced to approximately 40% of basal
      levels following insulin in both metyrapone and saline pretreated monkeys.
      Therefore, even though inhibition of cortisol synthesis leads to an increase in
      CRF messenger RNA in the paraventricular nucleus and a robust increase in ACTH
      secretion in rhesus monkeys, presumably due in part to increased neuroendocrine
      CRF secretion, LH secretion was not inhibited during either the acute or more
      chronic phase of corticotroph activation. Absence of LH inhibition was not due to
      low cortisol concentrations resulting from metyrapone because metyrapone did not
      prevent hypoglycemia-induced suppression of LH secretion. We conclude that
      increased neuroendocrine CRF secretion following metyrapone does not inhibit LH
      secretion under these conditions. Several explanations for this result are
      discussed.

PMID- 9165009
TI  - Gonadotropin-releasing hormone and pituitary adenylate cyclase-activating
      polypeptide affect levels of cyclic adenosine 3',5'-monophosphate-dependent
      protein kinase A (PKA) subunits in the clonal gonadotrope alphaT3-1 cells:
      evidence for cross-talk between PKA and protein kinase C pathways.
AB  - We have shown previously that protein kinase A (PKA) subunit levels are regulated
      by activation of PKA or protein kinase C (PKC) in anterior pituitary cells. GnRH
      also influenced PKA subunit levels, suggesting that hormonal regulation occurs in
      gonadotrophs, and therefore, we have reexamined this question using the clonal
      gonadotrope-derived cell line (alphaT3-1 cells). Western blot analysis, using
      specific immunoaffinity purified immunoglobulins, revealed expression of
      catalytic (Cat) and regulatory type I (RI) and type II (RII) subunits of PKA in
      these cells. Activation of adenylyl cyclase (AC) with forskolin, or of PKC with
      tetradecanoyl phorbol acetate (TPA), caused a rapid (detectable at 0.5-1 h) and
      concentration-dependent loss of all PKA subunits. Forskolin (10-100 microM)
      reduced Cat and RI by 60% and RII by 30%, whereas TPA (0.1-1 microM) reduced Cat
      and RII by 50% and RI by 40%. Simultaneous activation of PKA and PKC caused the
      expected dose-dependent reductions in Cat, and the effects of forskolin or TPA
      were nearly additive. RI and RII were reduced similarly by 10 nM TPA, whereas 100
      nM TPA tended to prevent the reduction of RI or RII caused by forskolin. GnRH,
      which activates phosphoinositidase C and not AC in these cells, caused a clear
      loss of Cat or RII at all concentrations tested and of RI at 0.1 nM. Pituitary
      adenylate cyclase-activating polypeptide 38, which acts via PVR-1 receptors to
      stimulate both phosphoinositidase C and AC in these cells, also caused a clear
      dose-dependent decrease in Cat, RI, and RII, although higher concentrations were
      needed for the latter effects. Together, the data demonstrate that catalytic and
      regulatory subunits of PKA are subject to both hormonal and receptor-independent
      regulation in alphaT3-1 cells, reinforcing the possibility that such effects
      occur in nonimmortalized gonadotropes. Whereas the effects of PKA activators very
      likely involve proteolytic degradation of the dissociated PKA holoenzyme, the
      effects of TPA and GnRH occur in the absence of cAMP elevation by unknown
      mechanisms. Whatever the mechanisms involved, the data reveal a mechanism for
      cross-talk between phosphoinositidase C and AC-mediated hormonal signals, in
      which PKC activation seems to play a pivotal role.

PMID- 9165010
TI  - Contrasted impact of maternal rat food restriction on the fetal endocrine
      pancreas.
AB  - The effects of food restriction of the mother (65% restriction of ad libitum food
      intake) on fetal and maternal insulin secretion and islet function were studied
      at 21 days gestation in three different rat populations: 1) undernourished from 0
      7 days gestation, 2) undernourished from 7-14 days gestation, and 3)
      undernourished from 14-21 days gestation. The body weights of mothers were
      decreased in groups 2 and 3 vs. those in control fed pregnant animals, and no
      changes in basal parameters were found in any group. A glucose tolerance test in
      mothers from group 3 showed a mild intolerance to glucose and a decreased islet
      insulin content, although islet stimulation in vitro with glucose alone or plus
      arginine showed a normal insulin secretory response. Body weight was decreased in
      fetuses from the three groups (P < 0.01), and pancreas weight was reduced only in
      group 3. Insulinemia was increased in groups 2 and 3, and pancreatic insulin
      content increased only in group 3. However, fetuses from mothers of group 3
      showed increased islet insulin content, increased response of insulin in vitro to
      glucose or glucose plus arginine, and hypertrophy of beta-cell mass. These
      results indicate, first, that the development of the fetal pancreas depends on a
      balanced maternal glucose homeostasis and, second, that adaptive maternal changes
      to undernutrition seem to induce alterations on the fetal endocrine pancreas,
      especially when food restriction is applied during the last week of gestation.

PMID- 9165011
TI  - Antilipolytic actions of vanadate and insulin in rat adipocytes mediated by
      distinctly different mechanisms.
AB  - Vanadate, which mimics the biological effects of insulin, also inhibits lipolysis
      in rat adipocytes. Here we demonstrate that the antilipolytic effect of vanadate
      differs from that of insulin at least by the five following criteria: 1) vanadate
      inhibits lipolysis mediated by high (supraphysiological) concentrations of
      catecholamines; 2) vanadate antagonizes (Bu)2cAMP-mediated lipolysis; 3) vanadate
      antagonizes isobutylmethylxanthine-dependent lipolysis, 4) vanadate inhibits
      lipolysis mediated by okadaic acid; and 5) wortmannin, which blocks the
      antilipolytic effect of insulin, fails to block vanadate-mediated antilipolysis.
      Vanadate does activate phosphoinositol 3-kinase, and wortmannin blocks this
      activation. Our working hypothesis assumes that all of the insulin-like effects
      of vanadate, including antilipolysis, are initiated by the inhibition of protein
      phosphotyrosine phosphatases (PTPases). Among documented PTPase inhibitors we
      found that VOSO4 (oxidation state +4), several organic vanadyl compounds (+4),
      zinc (Zn2+), tungstate (W), and molybdate (Mo) also had antilipolytic activity.
      The order of potency was vanadyl acetylacetonate > or = VOSO4 > or = NaVO3 > or =
      vanadyl-dipicolinate > Zn2+ >> W > Mo, and it correlated better with the
      inhibition of adipose membranal-PTPases in cell-free experiments. We have
      concluded that the antilipolytic effect of vanadate is 1) mechanistically
      distinct from that of insulin, 2) independent of phosphoinositol 3-kinase
      activation, and 3) independent of the lipolytic cascade. We also strongly suggest
      that the antilipolytic effect of vanadate emanates from inhibiting adipose
      membranal, rather than cytosolic PTPases, and present preliminary data showing
      distinct differences in catalysis between these two PTPase categories. Overall,
      the study indicates that antilipolysis can be manifested via alternative, insulin
      independent, signal-transducing pathways.

PMID- 9165012
TI  - Heparin-binding, highly basic regions within the thyroglobulin type-1 repeat of
      insulin-like growth factor (IGF)-binding proteins (IGFBPs) -3, -5, and -6 inhibit
      IGFBP-4 degradation.
AB  - MC3T3-E1 murine osteoblasts produce insulin-like growth factor (IGF)-binding
      protein-4 (IGFBP-4)-degrading proteinase activity, which is inhibited by IGFBP-3
      and a highly basic, C-terminal domain of IGFBP-3. Of all the other five IGFBPs,
      IGFBP-5 and -6 share the highest degree of homology with this domain of IGFBP-3;
      therefore, we investigated whether these two IGFBPs inhibit IGFBP-4 degradation.
      Both IGFBP-5 and IGFBP-6 inhibit the degradation of 125I-IGFBP-4 by MC3T3-E1
      conditioned media, and their inhibitory effects are variably reversed by IGFs.
      Synthetic peptides containing highly basic, C-terminal regions of IGFBP-5 and
      IGFBP-6 inhibit 125I-IGFBP-4 degradation, as does an homologous IGFBP-3 peptide,
      yet each peptide displays a different IC50, with the IGFBP-5 peptide being the
      most potent and the IGFBP-6 peptide being the least potent. In contrast, a
      homologous, yet neutral, IGFBP-4 peptide does not inhibit 125I-IGFBP-4
      proteolysis, confirming the role of basic residues in the inhibitory process. The
      IGFBP-3, -5, and -6 peptides, each of which contains the heparin-binding
      consensus sequence XBBBXXBX, bind heparin, yet the IGFBP-3 and -5 peptides bind
      heparin with the highest affinities, whereas the IGFBP-6 peptide binds heparin
      with approximately 10-fold less affinity. Consistent with these regions being
      involved in proteinase inhibition, heparin completely reverses their inhibitory
      effects on 125I-IGFBP-4 proteolysis. Together, these data demonstrate that IGFBP
      3, -5, and -6 can function as IGF-reversible inhibitors of IGFBP-4 proteolysis,
      likely through homologous, highly basic, heparin-binding domains contained within
      the conserved thyroglobulin type-1 motif present in the C-termini of these
      IGFBPs.

PMID- 9165013
TI  - The antiprogestins RU486 and ZK98299 affect follicle-stimulating hormone
      secretion differentially on estrus, but not on proestrus.
AB  - Previous in vivo studies from our laboratory indicated that administration of the
      antiprogestin RU486 on proestrus suppresses both the preovulatory gonadotropin
      surges and the secondary FSH surge, suggesting a role for the progesterone
      receptor (PR) in the generation of these surges. The present study was designed
      to test the effects of another antiprogestin, ZK98299, which has been reported to
      block the PR through a mechanism different from that of RU486, on gonadotropin
      secretion in vivo. RU486 and ZK98299 (2 and 6 mg/kg) were administered s.c. at
      1230 h on proestrus; uterine intraluminal fluid content, serum gonadotropins, and
      gonadotropin subunit messenger RNAs (mRNAs) were determined at 1830 h on
      proestrus and at 0900 h on estrus. At 1830 h on proestrus, both RU486 and ZK98299
      at both doses caused equal suppression of the preovulatory FSH surge and FSHbeta
      mRNA. Both antiprogestins also equally attenuated the preovulatory LH surge at
      this time, with the higher doses causing greater suppression. In contrast, at
      0900 h on estrus, the antiprogestins affected serum FSH differentially; only
      RU486 suppressed the secondary FSH surge despite the fact that both drugs
      prevented the release of uterine intraluminal fluid, confirming blockade of
      progesterone action at the level of the uterus. Neither drug had a significant
      effect on FSHbeta mRNA at 0900 h on estrus. ZK98299 at the higher dose caused a
      small, but significant, increase in serum LH. In a subsequent experiment, we
      compared the effects of RU486 and ZK98299 (6 mg/kg, s.c.), administered at 1230 h
      on proestrus, on serum FSH raised above the natural secondary FSH surge on the
      morning of estrus by passive immunization with an antiserum to inhibin-alpha
      (anti-I) at 1700 h on proestrus. Consistent with the results of the first
      experiment, both antiprogestins blocked the release of uterine intraluminal
      fluid, but only RU486 lowered serum FSH in both the normal sheep serum-treated
      controls and anti-I-treated rats; in contrast, ZK98299 actually increased serum
      FSH in the normal sheep serum-treated control animals. ZK98299 also increased
      FSHbeta mRNA in the control group; RU486, on the other hand, reduced FSHbeta mRNA
      only in the anti-I group. The results demonstrate unequivocally that whereas the
      effects of the two antiprogestins on serum FSH and FSHbeta mRNA are similar on
      proestrus, they are divergent on estrus. The data suggest that the functional
      state of the PR/transcriptional activation complex in the gonadotrope on the
      morning of estrus is different from that on the evening of proestrus.

PMID- 9165014
TI  - Transcriptional up-regulation of the human androgen receptor by androgen in bone
      cells.
AB  - Androgen regulation of androgen receptor (AR) expression has been observed in a
      variety of tissues, generally as inhibition, and is thought to attenuate cellular
      responses to androgen. AR is expressed in osteoblasts, the bone-forming cell,
      suggesting direct actions of androgens on bone. Here we characterized the effect
      of androgen exposure on AR gene expression in human osteoblastic SaOS-2 and U-2
      OS cells. Treatment of osteoblastic cells with the nonaromatizable androgen
      5alpha-dihydrotestosterone increased AR steady state messenger RNA levels in a
      time- and dose-dependent fashion. Reporter assays with 2.3 kilobases of the
      proximal 5'-flanking region of the human AR promoter linked to the
      chloramphenicol acetyltransferase gene in transfected cultures showed that up
      regulation of AR promoter activity by androgen was time and dose dependent.
      Treatment with other steroid hormones, including progesterone, 17beta-estradiol,
      and dexamethasone, was without effect. The antiandrogen hydroxyflutamide
      completely antagonized androgen up-regulation. Thus, in contrast to many other
      androgen target tissues, androgen exposure increases steady state AR messenger
      RNA levels in osteoblasts. This regulation occurs at least partially at the level
      of transcription, is mediated by the 5'-promoter region of the AR gene, and is
      dependent on functional AR. These results suggest that physiological
      concentrations of androgens have significant effects on AR expression in skeletal
      tissue.

PMID- 9165015
TI  - Aromatase inhibition impairs skeletal modeling and decreases bone mineral density
      in growing male rats.
AB  - Aromatization of androgens into estrogens may explain some of the skeletal action
      of androgens. We examined the effect of the aromatase inhibitor Vorozole (VOR) on
      skeletal growth and mineral accumulation in growing 6-week-old male Wistar rats.
      Rats were either Sham-operated (Sham) or Orchidectomized (Orch) and treated with
      or without the aromatase inhibitor VOR. One Sham-operated group was killed at
      Baseline (Base); the four other groups (Sham, Sham + VOR, Orch, Orch + VOR) were
      killed 18 weeks after surgery. As expected, all groups gained body weight, but
      body weight gain was significantly (-25%) lower in Orch, Orch + VOR, and Sham +
      VOR. Both bone formation, as assessed by serum osteocalcin, and bone resorption,
      as assessed by urinary (deoxy)pyridinoline, decreased significantly in all groups
      compared with Base. Orchidectomy resulted in a relative increase of biochemical
      markers of bone formation and resorption compared with Sham. Treatment with VOR,
      however, resulted only in a very moderate increase of (deoxy)pyridinoline
      compared with Sham. As expected, femoral length increased compared with Base, but
      orchidectomy reduced the relative growth of the femur whereas VOR did not
      influence femoral length. Ex vivo, densitometric and geometric properties of the
      femora were evaluated by peripheral computerized quantitative tomography (pQCT)
      and dual-energy x-ray absorptiometry (DXA). The lumbar vertebrae were measured by
      DXA. At the end of the experimental period, volumetric trabecular bone mineral
      density (vTBMD) measured at the distal end of the femur was significantly lower
      not only in both Orch groups but also in Sham + VOR. The decrease of cancellous
      bone density in Sham + VOR was lower than in the orchidectomized animals. A
      relative decrease of femoral inner and outer diameters compared with Sham and
      Base was observed in both Orch groups and in Sham + VOR, suggesting that both
      orchidectomy and VOR-treatment inhibited periosteal bone formation and endosteal
      bone resorption. Only orchidectomy, however, resulted in a decrease of cortical
      thickness. Bone area, mineral content, and density of both femora and lumbar
      vertebrae, measured by DXA, were decreased to a similar extent by VOR and Orch
      (bone mineral content of the femur was 467 +/- 18 mg in Orch and 461 +/- 10 mg in
      Sham +/- VOR vs. 521 +/- 11 mg in Sham; P < 0.001). In conclusion, treatment with
      the aromatase inhibitor VOR impairs body weight gain and skeletal modeling and
      decreases bone mineral density. Aromatase inhibition had similar final effects on
      bone mass and size as castration, but with less marked effects on bone turnover.

PMID- 9165016
TI  - Modulation of steroidogenesis by chloride ions in MA-10 mouse tumor Leydig cells:
      roles of calcium, protein synthesis, and the steroidogenic acute regulatory
      protein.
AB  - It has previously been shown that omission of extracellular chloride ions during
      culture of rat Leydig cells markedly enhances LH-stimulated steroidogenesis. In
      the present study, the mechanisms of the effect of chloride omission on (Bu)2cAMP
      stimulated steroidogenesis in MA-10 mouse Leydig tumor cells have been
      investigated. It was found that chloride omission enhanced progesterone
      production 2- and 4-fold in the absence and presence, respectively, of
      submaximally stimulating levels of (Bu)2cAMP (0.1 mM) during incubation for 2 h.
      This enhancement of stimulation increased continuously with time, because after 6
      h, (Bu)2cAMP-stimulated progesterone production was 15-fold higher in the absence
      of chloride. These effects were not found in the presence of maximum stimulating
      levels of (Bu)2cAMP (1 mM). Omission of calcium from the incubation medium
      decreased (Bu)2cAMP-stimulated progesterone production by over 70% in the
      presence and absence of chloride. Progesterone production was still enhanced by
      the omission of chloride in the absence of calcium, but the effects were less
      marked than those in the presence of calcium. Addition of the protein synthesis
      inhibitor, cycloheximide, completely inhibited (Bu)2cAMP-stimulated, but not
      basal, steroidogenesis in the absence and presence of chloride ions during 2- and
      6-h incubation. Total protein synthesis (measured by the incorporation of
      [3H]methionine) was 4-fold higher in cells incubated in chloride-free medium
      compared with that in cells incubated in chloride-replete medium in the presence
      of 0.1 mM (Bu)2cAMP. No effects were found on basal levels. Several proteins
      specific to the steroidogenic machinery were quantified in mitochondria isolated
      from cells incubated with and without chloride by Western blot analysis after
      separation by PAGE. Omission of chloride increased (4-fold) the level of the
      steroidogenic acute regulatory (StAR) protein in the cells incubated with
      (Bu)2cAMP (0.1 mM). There was no increase in either the levels or activities of
      cytochrome P450 cholesterol side-chain cleavage enzyme (cytP450scc) or 3beta
      hydroxysteroid dehydrogenase. No effects were found on the basal level of any of
      the proteins measured. These results are consistent with a cAMP-dependent
      regulatory role of chloride ion efflux in the control of steroidogenesis, which
      requires protein synthesis. It is proposed that this occurs by increases in StAR
      protein synthesis via a general increase in cAMP-dependent protein synthesis
      and/or by enhancement of the steroidogenic effects of StAR.

PMID- 9165017
TI  - Protein tyrosine phosphorylation influences adhesive junction assembly and
      follicular organization of cultured thyroid epithelial cells.
AB  - The follicular histoarchitecture of the thyroid forms the anatomical basis for
      thyroid physiology and is commonly disturbed in diseases of the thyroid. We have
      used cultured porcine thyroid cells to study thyroid epithelial morphogenesis and
      its regulation. When cultured in the presence of TSH, freshly isolated thyroid
      cells reorganize to form follicles within three-dimensional cell aggregates.
      However, when established follicles are washed into TSH-free medium, thyroid
      cells spread and migrate to convert follicles into confluent epithelioid
      monolayers, activating morphogenetic mechanisms, such as cell locomotility, that
      may be relevant to thyroid inflammation and tumor invasiveness. The phenomenon of
      follicle to monolayer conversion, therefore, provides an opportunity to identify
      morphogenetic mechanisms that 1) must be tonically inhibited to maintain
      follicular organization and 2) may contribute to pathogenetic disturbances of
      follicular architecture when functioning aberrantly. In this study we found that
      follicle to monolayer conversion is associated with an increase in cellular
      phosphotyrosine. This was particularly evident at nascent focal adhesions (cell
      substrate adhesive junctions) and later at cell-cell junctions. Focal adhesion
      assembly was accompanied by reorganization of the actin cytoskeleton, with the
      appearance of prominent stress fibers. Genistein, a potent inhibitor of protein
      tyrosine kinases, inhibited the accumulation of phosphotyrosine, focal adhesion
      assembly, and follicle to monolayer conversion. We conclude that tyrosine
      phosphorylation exerts an important influence on thyroid epithelial organization
      in culture, at least partly mediated through regulation of focal adhesion
      assembly.

PMID- 9165018
TI  - Binding and internalization of thyroglobulin: selectivity, pH dependence, and
      lack of tissue specificity.
AB  - Thyroglobulin (Tg), the precursor of thyroid hormones, follows a unique
      secretion, storage, and recapture pathway. The first steps of recapture were
      studied by investigating the binding of 125I-labeled Tg on the apical surface of
      inside-out follicles and its internalization. The selectivity of the process was
      assessed by using molecules other than Tg and/or nonthyroid cells. Tg binding to
      the apical surface of thyroid inside-out follicles is selective relative to the
      binding of other molecules. It increases sharply over pH 8.0 and occurs through
      specific sites of moderately high affinity (Kd = approximately 200 nM; 2 x 10(4)
      sites/cells). At pH < 8.0 it occurs through numerous sites of very low affinity
      considered nonspecific. Endocytosis, although weak under our conditions,
      increases at pH 8.0 concomitantly with binding. Over pH 8.2, however, some
      inhibition occurs. Surprisingly, Tg binding and endocytosis are not tissue
      specific, as they showed the same properties on thyroid inside-out follicles and
      Madin-Darby canine kidney or Chinese hamster ovary cells. Thus, a selective
      uptake of Tg mediates its recapture by thyroid cells. This selectivity is an
      intrinsic Tg property, not dependent on the thyrocyte apical surface, as it was
      observed with Madin-Darby canine kidney and Chinese hamster ovary cells. Given
      the pH effect observed, we suggest that Tg binding is a regulated phenomenon and
      that, through luminal pH control, it can vary from a basal level at neutral pH to
      a stimulated level over pH 8.0.

PMID- 9165020
TI  - Differential gene expression of cytochrome P450 11beta-hydroxylase in rat adrenal
      cortex after in vivo activation.
AB  - In situ hybridization histochemistry was used to monitor the expression of 3beta
      hydroxysteroid dehydrogenase, delta4-isomerase (3betaHSD) and cytochrome P450
      11beta-hydroxylase (P45011beta) messenger RNA (mRNA) in adult rat adrenals after
      stimulation in vivo. In Exp 1, adrenals were collected from rats injected with
      saline or ACTH for 1, 2, 3, or 4 days. Adrenal sections from saline-treated rats
      showed uniform expression of 3betaHSD mRNA that extended from the adrenal capsule
      to the medullary border. In contrast, P45011beta mRNA showed high levels in the
      outer fasciculata and low levels in the inner fasciculata/reticularis. In
      response to ACTH, the integrated density of 3betaHSD hybridization did not
      increase until 4 days. The integrated density of P45011beta hybridization
      increased in ACTH-treated rats between 1-4 days due to increased hybridization in
      the inner fasciculata/reticularis. In Exp 2, rats were treated with ACTH or
      saline, and adrenals were harvested at 4, 8, or 24 h. The hybridization density
      of 3betaHSD did not change after ACTH or saline injection. Increased expression
      of P45011beta mRNA was observed at 4 and 8 h, but not 24 h post-ACTH. In Exp 3,
      to determine the response to acute stress, adrenals were collected from rats 24 h
      after surgical laparotomy. The integrated density of 3betaHSD labeling did not
      change, whereas both hybridization area and mean density of P45011beta increased.
      Increased expression of P45011beta mRNA was observed in the inner fasciculata
      similar to that observed after ACTH injection. In addition, adrenal cells were
      more responsive to ACTH in vitro after surgical stress. These results suggest
      that the rat adrenal cortex can respond to acute stress by up-regulation of the
      expression of steroidogenic enzyme genes and that this occurs in part by
      increasing the number of cells actively expressing P45011beta mRNA. The adrenal
      response after stress most likely results at least in part from stimulation by
      ACTH. These findings suggest that changes in adrenal steroidogenesis in response
      to ACTH may result from recruitment of steroidogenic cells to synthesize and
      secrete corticosteroids.

PMID- 9165021
TI  - Cloning and characterization of the vitamin D receptor from Xenopus laevis.
AB  - The Vitamin D receptor (VDR), a member of the nuclear receptor superfamily,
      mediates the effects of 1,25-dihydroxyvitamin D3 on mineral ion homeostasis.
      Although the mammalian and avian VDRs have been extensively studied, little is
      known about the VDR in lower vertebrate species. To address this, we have
      isolated the Xenopus laevis VDR (xVDR) complementary DNA. Overall, the xVDR
      shares 79%, 73%, 73%, and 75% identity at the amino acid level with the chicken,
      mouse, rat, and human VDRs, respectively. The amino acid residues and subdomains
      important for DNA binding, hormone binding, dimerization, and transactivation are
      mostly conserved among all VDR species. The xVDR polypeptide can heterodimerize
      with the mouse retinoid X receptor alpha, bind to the rat osteocalcin vitamin D
      response element (VDRE), and induce vitamin D-dependent transactivation in
      transfected mammalian cells. Northern analysis reveals two xVDR messenger RNA
      species of 2.2 kb and 1.8 kb in stage 60 Xenopus tissues. In the adult, xVDR
      expression is detected in many tissues including kidney, intestine, skin, and
      bone. During Xenopus development, xVDR messenger RNA first appears at
      developmental stage 13 (pre-neurulation), increasing to maximum at stages 57-61
      (metamorphosis). Our data demonstrate that, in Xenopus, VDR expression is
      developmentally regulated and that the vitamin D endocrine system is highly
      conserved during evolution.

PMID- 9165019
TI  - Endothelins stimulate deoxyribonucleic acid synthesis and cell proliferation in
      rat adrenal zona glomerulosa, acting through an endothelin A receptor coupled
      with protein kinase C- and tyrosine kinase-dependent signaling pathways.
AB  - The effects of endothelins (ET) on the proliferative activity of the rat adrenal
      cortex have been investigated in vivo, using an in situ perfusion technique of
      the intact left gland. The chemicals were dissolved in the perfusion medium, and
      the perfusion continued for 120 min. ET-1 concentration dependently increased the
      mitotic index and [3H]thymidine incorporation into DNA in the zona glomerulosa
      (ZG; 6- and 3-fold increases, respectively, at a 10(-8) M concentration), but not
      in the inner adrenocortical layers, where the basal proliferative activity was
      negligible. The effect of 10(-8) M ET-1 was blocked by the ETA receptor
      antagonist BQ-123, whereas the ETB receptor antagonist BQ-788 was ineffective. ET
      2 and ET-3 (10(-8) M) enhanced DNA synthesis in the ZG, but their effects were
      less intense than that of 10(-8) M ET-1 and were directly related to their
      binding potency for the ETA receptor subtype (ET-1 > ET-2 >> ET-3). The selective
      ETB receptor agonists BQ-3020, IRL-1620, and sarafotoxin-6B were ineffective. The
      ZG proliferogenic action of 10(-8) M ET-1 was reversed by both the protein kinase
      C inhibitor Ro31-8220 and the tyrosine kinase inhibitor tyrphostin-23; a complete
      blockade was obtained at a 10(-6)-M concentration of each inhibitor. In contrast,
      neither the protein kinase A inhibitor H-89 (10(-5) M) nor the cyclooxygenase and
      lipoxygenase inhibitors indomethacin and phenidone (10(-5) M) affected ET-1
      action. Collectively, our findings indicate that ETs stimulate the proliferation
      of rat adrenal ZG cells, acting through ETA receptors coupled with protein kinase
      C- and tyrosine kinase-dependent signaling pathways. The results of the present
      study are in keeping with the view that in mammals, ZG is the proliferative layer
      involved in the maintenance of growth of the entire adrenal cortex and with the
      previous autoradiographic demonstration that ZG is the only adrenocortical layer
      provided with ETA receptors.

PMID- 9165022
TI  - Effects of gestation on enzymes controlling aldosterone synthesis in the rat
      adrenal.
AB  - In the present study, the effects of gestation on various enzymes implicated in
      corticosteroid synthesis were evaluated in adrenal zona glomerulosa and zona
      fasciculata-reticularis of the Sprague-Dawley rat. The activity and expression of
      cholesterol side-chain cleavage cytochrome P450, 11beta-hydroxylase cytochrome
      P450, and aldosterone synthase cytochrome P450 (P450aldo) were analyzed. Plasma
      aldosterone levels were increased significantly at 22 days gestation (n = 10) and
      fell below the nonpregnant levels at 18-36 h postpartum (n = 11). The activity
      and expression of 11beta-hydroxylase cytochrome P450 and cholesterol side-chain
      cleavage cytochrome P450 were not modified by gestation. P450aldo activity
      increased at 14 days gestation (n = 4) and returned to the prepregnancy level at
      2 weeks postpartum (n = 5). As shown by Northern blot analysis (n = 3), P450aldo
      messenger RNA increased significantly at 22 days gestation and decreased 18-36 h
      postpartum. We clearly demonstrated that elevated plasma aldosterone levels
      during pregnancy are associated with augmented activity and messenger RNA levels
      of P450aldo in the zona glomerulosa.

PMID- 9165023
TI  - Correlation of the activation of Ca2+/calmodulin-dependent protein kinase II with
      the initiation of insulin secretion from perifused pancreatic islets.
AB  - An experimental procedure has been designed to permit the simultaneous assessment
      of the activation status of the multifunctional Ca2+/calmodulin-dependent protein
      kinase II (CaM kinase II) with insulin secretion in perifused islets. By this
      procedure, the activation of CaM kinase II by glucose correlated closely with the
      initial and sustained phases of insulin secretion within a 30-min test period. By
      contrast, islets (160-200/tube) in static incubations neither supported second
      phase insulin secretion nor CaM kinase II activation beyond 10-15 min. This was
      not the result of the accumulation of insulin, because the introduction of
      insulin (40-160 ng/ml) into the perifusion medium failed to mimic the suppression
      of glucose-induced insulin secretion or CaM kinase II activation. A similar
      addition of SRIF (0.01-1 microM) or epinephrine (1 microM) profoundly suppressed
      insulin secretion although failing to significantly influence CaM kinase II
      activation. Finally, on withdrawal of glucose from perifused islets, insulin
      secretion rapidly returned to basal rates, but CaM kinase II deactivation was
      significantly delayed. The correlation of kinase activation with the initiation
      of insulin secretion suggests that CaM kinase II may be important in the
      regulation of glucose-induced insulin secretion. The observed dissociation of
      these parameters in the presence of inhibitory hormones or after the withdrawal
      of a glucose stimulus, however, suggests that the kinase is not directly involved
      in the final steps of insulin exocytosis.

PMID- 9165024
TI  - Coincidental changes in behavior and plasma cortisol in unrestrained pigs after
      intracerebroventricular injection of tumor necrosis factor-alpha.
AB  - The coincidental behavioral and physiological responses to inflammatory stimuli
      administered either peripherally or centrally were evaluated. In the first study,
      twenty castrated male pigs were injected ip with 0, 0.5, 5, or 50 microg/kg BW
      lipopolysaccharide (LPS). Body temperature was monitored telemetrically, and
      serial blood samples were collected via an indwelling jugular catheter for
      determination of plasma cortisol and tumor necrosis factor-alpha (TNF-alpha)
      concentrations. Sickness behaviors were measured during 10-min tests at 0, 2, 4,
      8, 12, and 24 h post injection. The 5 and 50 microg/kg doses of LPS increased
      plasma concentrations of cortisol and TNF-alpha, while inducing anorexia,
      hypersomnia, and fever. In contrast, although 0.5 microg/kg LPS induced acute
      anorexia, hypersomnia, and fever, it did not increase plasma TNF-alpha; and the
      cortisol response was small and transient, suggesting the behavioral system in
      pigs is more responsive to LPS than the hypothalamic-pituitary-adrenal (HPA)
      axis. Because LPS-induced behavior and activation of the HPA axis involve
      proinflammatory cytokines in the brain, in a second study, unrestrained pigs with
      jugular catheters were injected intracerebroventricularly (I.C.V.) with
      recombinant porcine TNF-alpha. Vehicle or TNF-alpha (0, 5, or 50 ng/kg) was
      injected I.C.V., and plasma cortisol and behavior were determined as before. Pigs
      injected I.C.V. with 50 ng/kg TNF-alpha showed anorexia, hypersomnia, and an
      abrupt increase in plasma cortisol concentration. Whereas 5 ng/kg TNF-alpha
      I.C.V. also induced marked sickness behavior, it failed to stimulate the HPA
      axis, as indicated by plasma cortisol levels. That there was a distinct
      difference in the magnitude of behavioral and endocrine responses to LPS and TNF
      alpha suggests that different systems that are responsive to inflammatory stimuli
      exhibit different sensitivities.

PMID- 9165026
TI  - Two protochordate genes encode pituitary adenylate cyclase-activating polypeptide
      and related family members.
AB  - To address the origin of the glucagon superfamily, we isolated and sequenced the
      complementary DNA and partial gene that encode pituitary adenylate cyclase
      activating polypeptide (PACAP) from a protochordate (tunicate), a sister group of
      the amphioxus and vertebrates, but one that evolved before the amphioxus. This is
      the first report of any superfamily member sequenced from an invertebrate.
      Transcription of the tunicate pacap1 gene results in a messenger RNA that is 507
      bp. The gene contains 3 exons that encode a signal peptide, GRF-like peptide(1
      27), and PACAP(1-27). The tunicate GRF-like peptide has 59% identity with human
      GRF, whereas the deduced amino acids of tunicate PACAP(1-27) have 96% identity
      with the ovine, human, and salmon PACAP(1-27) forms. Another complementary DNA
      clone pacap2 was isolated and shown to contain 4 exons that encode a signal
      peptide, a cryptic peptide, and two peptides that are clearly members of the
      glucagon superfamily. One of the peptides has 89% sequence identity to the
      tunicate PACAP encoded in pacap1. A comparison of the two structurally related
      PACAP clones, each encoding two peptides on separate exons, shows high inter- and
      intraexon nucleotide sequence identity. Sequence analysis suggests that an exon
      duplication followed by a gene duplication was responsible for the origin of the
      two genes. It is argued that the PACAP gene is derived from the protochordate
      ancestral genes that led to the vertebrate forms of GRF and PACAP.

PMID- 9165025
TI  - Transcriptional induction of cyclooxygenase-2 in osteoblasts is involved in
      interleukin-6-induced osteoclast formation.
AB  - Interleukin-6 (IL-6) induces osteoclast-like cell (osteoclast) formation in a
      dose-dependent fashion in cocultures of mouse bone marrow cells and osteoblastic
      cells when soluble IL-6 receptor (sIL-6R) is present. Simultaneous treatment with
      submaximal doses of IL-1alpha and IL-6 with sIL-6R caused marked induction of
      osteoclast formation and PGE2 synthesis. These effects were suppressed by adding
      neutralizing antibodies against IL-1alpha or IL-6R and were totally abolished by
      adding nonsteroidal antiinflammatory drugs, such as indomethacin and a selective
      cyclooxygenase-2 (COX-2) inhibitor (NS398). In mouse osteoblastic cells, both IL
      1alpha and IL-6 with sIL-6R markedly induced messenger RNA expression of COX-2,
      but not COX-1, as determined by Northern blot analysis, and luciferase activity
      in cells stably transfected with a COX-2 promoter-luciferase fusion construct. IL
      6 and sIL-6R, when added separately, did not stimulate COX-2 messenger RNA
      expression. Simultaneous addition of IL-1alpha and IL-6 with sIL-6R to osteoblast
      cultures cooperatively induced transcription of COX-2, which was associated with
      a marked increase in COX activity measured by the conversion of arachidonic acid
      into PGE2. The increased PGE2 synthesis by osteoblasts may play an important role
      in osteoclastogenesis induced by submaximal doses of IL-1 and IL-6.

PMID- 9165027
TI  - Association of N-ethylmaleimide sensitive fusion (NSF) protein and soluble NSF
      attachment proteins-alpha and -gamma with glucose transporter-4-containing
      vesicles in primary rat adipocytes.
AB  - To investigate the role of N-ethylmaleimide sensitive fusion protein (NSF) and
      soluble NSF attachment proteins (SNAP)-containing fusion complexes in glucose
      transporter-4 (GLUT4) membrane trafficking, the subcellular distributions of NSF,
      alpha-SNAP, and gamma-SNAP in primary rat adipocytes were determined. A large
      fraction of the NSF and SNAPs were associated with intracellular membranes,
      distributed between the low-density microsomes (LDM) and high-density microsomes.
      Very little of the NSF and SNAPs were associated with the plasma membrane
      fraction. This distribution did not change after insulin stimulation.
      Approximately 75% of the NSF and SNAPs in the LDM fraction were
      coimmunoprecipitated with 85% of the GLUT4 and 60% of the vesicle associated
      membrane proteins (VAMPs; synaptobrevins) VAMP-2 and cellubrevin in anti-GLUT4
      immunoadsorptions. In contrast to NSF and the SNAPs, the beta-coatomer protein
      (beta-COP) found in the LDM fraction was excluded from GLUT4 vesicles. When LDM
      fractions were solubilized with Thesit (octaethylene glycol dodecyl ether) or
      Triton X-100, approximately 40% of the alpha-SNAP was colocalized with NSF on
      glycerol gradients in large (approximately 20S), ATP-sensitive complexes. VAMP-2
      and cellubrevin are concentrated in the LDM fractions and in GLUT4 vesicles; both
      were excluded from these complexes. These data suggest that the steady state
      association of NSF and the SNAPs with GLUT4 vesicles and cell membranes is
      independent of the formation of fusion complexes.

PMID- 9165029
TI  - Gi3 mediates somatostatin-induced activation of an inwardly rectifying K+ current
      in human growth hormone-secreting adenoma cells.
AB  - SRIF activates an inwardly rectifying K+ current in human GH-secreting adenoma
      cells. Activation of this K+ current induces hyperpolarization of the membrane
      and abolishment of action potential firing. This mechanism is an essential
      mechanism for SRIF-induced decrease in intracellular Ca2+ concentration and
      inhibition of GH secretion. The activation of the inwardly rectifying K+ current
      is mediated by a pertussis toxin-sensitive G protein. In this article, the
      expression of the pertussis toxin-sensitive G protein alpha-subunits in the human
      GH-secreting adenoma cells were analyzed by RT-PCR, and the G protein transducing
      the SRIF-induced activation of this inwardly rectifying K+ current was
      investigated. RT-PCR of the messenger RNA from two human GH-secreting adenomas
      revealed that all G alpha(i1), G alpha(i2), G alpha(i3), and G alpha(o) were
      expressed in these adenomas. Primary cultured cells from these two adenoma cells
      were investigated under the voltage clamp of the whole-cell mode. Specific
      antibodies against the carboxyl terminus of G protein alpha-subunits were
      microinjected into the cells. Microinjection of antibody against the carboxyl
      terminal sequence of G alpha(i3) attenuated the SRIF-induced activation of the
      inwardly rectifying K+ current, whereas antibody against the common carboxyl
      terminal sequence of G alpha(i1) and G alpha(i2) did not. These data indicate
      that the G protein transducing the SRIF-induced activation of the inwardly
      rectifying K+ current is Gi3.

PMID- 9165028
TI  - The effect of modulating the glycogen-associated regulatory subunit of protein
      phosphatase-1 on insulin action in rat skeletal muscle cells.
AB  - Recent studies from this laboratory have shown that insulin rapidly stimulates a
      membranous protein phosphatase-1 (PP-1) in cultured rat skeletal muscle cells and
      isolated rat adipocytes. Stimulation of PP-1 is accompanied by the
      phosphorylation of a 160-kDa regulatory subunit of PP-1 (PP-1G). To further
      evaluate the exact role of this subunit in insulin action, L6 rat skeletal muscle
      cells were stably transfected with a vector containing the gene for PP-1G in the
      sense and antisense orientations. Transfection with the vector containing the PP
      1G gene in the sense orientation yielded three stable clones with a 4- to 6-fold
      increase in PP-1G protein expression compared to those of wild-type L6 cells and
      neo control cells harboring an empty expression vector. Compared to the neo
      control, overexpression of PP-1G resulted in a 3-fold increase in insulin
      stimulated PP-1 catalytic activity bound to PP-1G immunoprecipitates. These cell
      lines were examined for insulin's effect on glucose uptake, glycogen synthase
      activity, and glycogen synthesis. Insulin treatment resulted in an approximately
      2-fold increase in 2-deoxyglucose uptake in recombinant cells compared to control
      cells (P < 0.05). This increase in 2-deoxyglucose transport was accompanied by an
      approximately 2-fold increase in insulin-stimulated glycogen synthase fractional
      activity (P < 0.05) and a 2- to 4-fold increase in insulin-stimulated glycogen
      synthesis compared to control cells. In conjunction with these observations, we
      found that an 85% depletion of endogenous PP-1G, using antisense constructs,
      resulted in a complete lack of PP-1 activation and an inhibition of basal and
      insulin-stimulated glucose transport. We conclude that the PP-1G holoenzyme is
      the major phosphatase regulated by insulin in vivo and plays an important role in
      insulin-stimulated glycogen synthesis by regulating the catalytic activity of
      bound PP-1.

PMID- 9165030
TI  - Characterization of the atrial natriuretic peptide system in the oviduct.
AB  - The atrial natriuretic peptide (ANP) gene is expressed in several extraatrial
      tissues in which ANP may be involved in the regulation of autocrine or paracrine
      functions. In the ovary, the synthesis of ANP, its binding sites, and a
      physiological role were found. The ANP system in the oviduct, however, is yet to
      be defined. The purpose of the present study was to determine whether the ANP
      system is present in the oviduct and then to define its function. The serial
      dilution curves of oviductal extracts in rat and rabbit were parallel to the
      standard curve of ANP. Molecular profiles using reverse phase HPLC indicated that
      the prohormone and processed circulating peptide were the main forms present. The
      immunoreactive ANP content of the oviduct was 27.07 +/- 4.41 pg/mg tissue wet wt
      (1.19 +/- 0.19 ng/oviduct; n = 10; at metestrus) in rats and 1.21 +/- 0.12 pg/mg
      tissue wet wt (0.15 +/- 0.01 ng/oviduct; n 12) in rabbits. In adult 4-day cycling
      rats, the immunoreactive ANP contents in oviducts had a cyclic change
      characterized by the lowest level at proestrus (14.59 +/- 3.24 pg/mg; n = 12). A
      distinct and strong ANP immunoreactivity was found in the mucosal layer of rat
      oviduct, and ANP messenger RNA was also detected in the oviduct by reverse
      transcriptase-PCR. Specific high affinity binding sites for iodinated rat ANP
      ([125I]rANP) were observed in the mucosal layer of the oviduct in rats and
      rabbits. Specific [125I]rANP bindings localized in the mucosal layer of rabbit
      oviduct showed an apparent dissociation constant (Kd) of 18.69 +/- 5.55 nM and a
      maximal binding capacity of 14.85 +/- 6.19 fmol/mm2. These specific [125I]rANP
      bindings were not reversed by des-[Gln18,Ser19,Gly20,Leu21,Gly22]ANP-(4- 23) as a
      selective ligand of clearance receptor. Synthetic ANP inhibited both the
      frequency and amplitude of basal motility of rabbit oviduct in a dose-dependent
      manner. These results suggest that the oviduct has its own ANP system, and the
      system is involved in the regulation of oviductal motility.

PMID- 9165031
TI  - Preantral ovarian follicles in serum-free culture: suppression of apoptosis after
      activation of the cyclic guanosine 3',5'-monophosphate pathway and stimulation of
      growth and differentiation by follicle-stimulating hormone.
AB  - Progression of preantral follicle development is essential to further follicle
      maturation and ovulation, but there are few models for studying the regulation of
      preantral follicle survival and growth. We have evaluated preantral follicle
      survival in vivo and in vitro, and have developed a serum-free rat follicle
      culture system that can be used to characterize the regulation of preantral
      follicle growth and differentiation. Analysis of ovarian cell DNA fragmentation
      during the first wave of follicle growth in the infantile rat indicated
      negligible apoptosis up to day 16 of age. However, a major increase in apoptosis
      was found by day 18, a time point associated with the appearance of large antral
      follicles. In situ analysis confirmed that apoptotic DNA fragments were limited
      to antral follicles. Culture of individual preantral follicles mechanically
      dissected from ovaries of 12- or 14-day-old rats in serum-free conditions led to
      major increases in follicle cell apoptosis, similar to that seen in cultures of
      antral and preovulatory follicles. In contrast to antral and preovulatory
      follicles, treatment of preantral follicles with gonadotropins or cAMP analogs
      did not prevent apoptosis. However, treatment with 8-bromo-cGMP or 10% serum
      suppressed apoptosis by 75% in cultured preantral follicles. In situ analysis
      identified granulosa cells as the cell type susceptible to apoptosis regulation.
      Taking advantage of the ability of the cGMP analog to suppress apoptosis, we
      evaluated the potential of FSH as a growth factor. In the absence of serum, FSH
      treatment for 48 h did not affect follicle size compared to controls; however,
      treatment with the cGMP analog together with FSH increased follicle diameter
      (13%; P < 0.01) and viable cells (2.4-fold; P < 0.01) compared to control values.
      Immunoblot analysis further indicated that the inhibin-alpha content of the
      cultured follicles was increased by treatment with the combination of FSH and 8
      bromo-cGMP, demonstrating the induction of follicle cell differentiation during
      culture. Therefore, we demonstrated that activation of the cGMP pathway promotes
      the survival of cultured preantral follicles and that in the presence of alpha
      cGMP analog, FSH is a growth and differentiation factor for preantral follicles.
      The present serum-free follicle culture model system will be useful in further
      evaluation of the regulation of growth and differentiation of preantral
      follicles.

PMID- 9165033
TI  - Identification of a kinetically distinct activity of 11beta-hydroxysteroid
      dehydrogenase in rat Leydig cells.
AB  - Leydig cells are susceptible to direct glucocorticoid-mediated inhibition of
      testosterone biosynthesis but can counteract the inhibition through 11beta
      hydroxysteroid dehydrogenase (11beta-HSD), which oxidatively inactivates
      glucocorticoids. Of the two isoforms of 11beta-HSD that have been identified,
      type I is an NADP(H)-dependent oxidoreductase that is relatively insensitive to
      inhibition by end product and carbenoxolone (CBX). The type I form has been shown
      to be predominantly reductive in liver parenchymal cells and other tissues. In
      contrast, type II, which is postulated to confer specificity in mineralocorticoid
      receptor (MR)-mediated responses, acts as an NAD-dependent oxidase that is
      potently inhibited by both end product and CBX. The identity of the 11beta-HSD
      isoform in Leydig cells is uncertain, because the protein in this cell is
      recognized by an anti-type I 11beta-HSD antibody, but the activity is primarily
      oxidative, more closely resembling type II. The goal of the present study was to
      determine whether the kinetic properties of 11beta-HSD in Leydig cells are
      consistent with type I, type II, or neither. Leydig cells were purified from male
      Sprague-Dawley rats (250 g), and 11beta-HSD was evaluated in Leydig cells by
      measuring rates of oxidation and reduction, cofactor preference, and inhibition
      by end product and CBX. Leydig cells were assayed for type I and II 11beta-HSD
      and MR messenger RNAs (mRNAs), and for type I 11beta-HSD protein. Leydig cell
      11beta-HSD had bidirectional catalytic activity that was NADP(H)-dependent. This
      is consistent with the hypothesis that type I 11beta-HSD is present in rat Leydig
      cells. However, unlike the type I 11beta-HSD in liver parenchymal cells, the
      Leydig cell 11beta-HSD was predominantly oxidative. Moreover, analysis of
      kinetics revealed two components, the first being low a Michaelis-Menten constant
      (Km) NADP-dependent oxidative activity with a Km of 41.5 +/- 9.3 nM and maximum
      velocity (Vmax) of 7.1 +/- 1.2 pmol x min x 10(6) cells. The second component
      consisted of high Km activities that were consistent with type I:NADP-dependent
      oxidative activity with Km of 5.87 +/- 0.46 microM and Vmax of 419 +/- 17 pmol x
      min x 10(6) cells, and NADPH-dependent reductive activity with Km of 0.892 +/-
      0.051 microM and Vmax of 117 +/- 6 pmol x min x 10(6) cells. The results for end
      product and CBX inhibition were also inconsistent with a single kinetic activity
      in Leydig cells. Type I 11beta-HSD mRNA and protein were both present in Leydig
      cells, whereas type II mRNA was undetectable. We conclude that the low Km NADP
      dependent oxidative activity of 11beta-HSD in Leydig cells does not confirm to
      the established characteristics of type I and may reside in a new form of this
      protein. We also demonstrated the presence of the mRNA for MR in Leydig cells,
      and the low Km component could allow for specificity in MR-mediated responses.

PMID- 9165032
TI  - Bovine activin receptor type IIB messenger ribonucleic acid displays alternative
      splicing involving a sequence homologous to Src-homology 3 domain binding sites.
AB  - Activins are implicated in a variety of biological effects, particularly in
      reproductive processes such as embryonic development and folliculogenesis.
      Breakthroughs in the elucidation of the activin signal transduction mechanism
      were achieved with the characterization of the activin receptors, and the recent
      identification of cytoplasmic factors apparently involved in the signaling
      process. The present studies were undertaken to further analyze the activin
      signaling pathway. The complementary DNA coding for the bovine activin receptor
      type IIB (bActRIIB) was amplified by RT-PCR from corpus luteum and pituitary RNA,
      and cloned to characterize its role in activin signal transduction. Two
      complementary DNA isoforms (bActRIIB2 and bActRIIB5) were detected, coding for
      512 amino acids and 498 amino acids, respectively. The shortest isoform lacked a
      sequence encoding a 14-amino acid stretch very rich in proline residues, located
      between the transmembrane region and the intracellular kinase domain. Intron
      sequencing and ribonuclease protection assay demonstrated that alternative
      splicing is responsible for the generation of these bActRIIB isoforms. This
      alternative splicing event is unique in that it has not been observed in other
      species, including the mouse, in which extensive alternative splicing of the
      ActRIIB messenger RNA is described. Comparison of this alternative sequence with
      other known proline-rich sequences showed that it has characteristics of a Src
      homology 3 domain (SH3) binding site. Coprecipitation experiments have identified
      two proteins of 69 kDa and 71 kDa from an uterine endometrial cell line,
      specifically interacting with the short bActRIIB alternative proline-rich
      sequence. These results suggest that bActRIIB could have a protein-protein
      interaction, through its putative SH3 binding site, with at least two
      intracellular SH3-containing proteins.

PMID- 9165034
TI  - Modulation of epinephrine-stimulated gluconeogenesis by insulin in hepatocytes
      isolated from genetically obese (fa/fa) Zucker rats.
AB  - Genetically obese (fa/fa) Zucker rats present an impaired response of hepatic
      glucose production to the inhibition by insulin. In this work, we have
      investigated the modulation by this hormone of epinephrine-stimulated
      gluconeogenesis, in hepatocytes isolated from obese (fa/fa) rats and their lean
      (Fa/-) littermates. Epinephrine (1 microM) caused a maximal stimulation of
      [14C]lactate conversion to [14C]glucose in hepatocytes isolated from either obese
      or lean animals. The stimulation of gluconeogenesis by epinephrine was
      accompanied by a significant reduction of fructose 2,6-bisphosphate levels, an
      inactivation of both pyruvate kinase and 6-phosphofructo 2-kinase, and by a 2
      fold increase in the cellular concentrations of cAMP. The presence of insulin in
      the incubation medium antagonized, in a concentration-dependent manner, the
      effects of epinephrine. In hepatocytes isolated from lean rats, the reversion
      caused by insulin was complete, the concentration required for half-maximal
      insulin action ranging from 0.22 to 0.56 nM. In contrast, in obese rat
      hepatocytes, insulin only partially blocked epinephrine-mediated effects, and the
      sensitivity to insulin was 2- to 4-fold lower, as indicated by the corresponding
      half-maximal insulin action values. Furthermore, insulin (10 nM) almost
      completely blocked the increase in cAMP levels induced by epinephrine in lean rat
      hepatocytes, whereas it only provoked a small and nonsignificant reduction of
      epinephrine-stimulated levels of the cyclic nucleotide in hepatocytes obtained
      from obese rats.

PMID- 9165035
TI  - Parathyroid hormone increases bone formation and improves mineral balance in
      vitamin D-deficient female rats.
AB  - The present study was designed to investigate whether enhanced bone formation due
      to intermittent PTH administration is dependent on vitamin D metabolites. Forty
      eight female Sprague-Dawley rats were randomized into four groups: 1) vitamin D
      sufficient, saline-injected (+D Sal); 2) vitamin D-sufficient, human (h) PTH-(1
      38)-treated (+D PTH); 3) vitamin D-deficient, saline-injected (-D Sal); and 4)
      vitamin D-deficient, hPTH-(1-38)-treated (-D PTH) animals. The -D diet contained
      2% calcium (Ca), 1.25% phosphorus (P), and 20% lactose to maintain normocalcemia
      and normophosphatemia despite vitamin D deficiency. The +D diet contained 0.8%
      Ca, 0.5% P, 20% lactose, and 1000 IU/kg vitamin D. After 45 days of either diet,
      the rats were injected with 50 microg/kg BW PTH or saline, s.c., daily for 2
      weeks. Serum Ca, Mg, P, albumin, and creatinine were similar in all groups. PTH
      administration decreased endogenous PTH concentrations in the -D PTH compared
      with those in the - D Sal group. Serum alkaline phosphatase activity, bone mass
      measurements, dual energy x-ray absortiometric analysis of mineral density, and
      mechanical testing values in vertebrae and femora of the -D Sal animals did not
      significantly differ from those in +D Sal animals. Moreover, in both diet groups,
      PTH improved bone biochemical activity (as assessed by serum alkaline
      phosphatase), bone mass, mineral density, and biomechanical properties. These
      results indicate that mineral supply, more than vitamin D itself, may be
      important for normal bone mineralization and to enable PTH to enhance bone
      formation. A balance study performed during the last 3 days of the experiment
      revealed that PTH increased apparent intestinal magnesium absorption in the +D
      group only. Ca and P retention, however, were augmented in both diet groups after
      PTH treatment. In conclusion, in normocalcemic and normophosphatemic -D rats, PTH
      treatment reduced the increased endogenous hormone concentration and improved Ca
      and P retention. Furthermore, PTH may have a vitamin D-dependent influence on
      intestinal magnesium absorption. Finally, short term PTH treatment is anabolic in
      bone of vitamin D-deficient rats when adequate mineral amounts are provided in
      the diet.

PMID- 9165036
TI  - Glucocorticoids regulate pituitary growth hormone-releasing hormone receptor
      messenger ribonucleic acid expression.
AB  - Glucocorticoids regulate GH synthesis and secretion by influencing both
      hypothalamic and pituitary function. With respect to GH-releasing hormone (GHRH),
      an important GH secretagogue, glucocorticoids are reported not only to suppress
      hypothalamic GHRH expression but also to augment pituitary responsiveness to
      GHRH. To investigate further this latter observation, we have determined the
      effects of this steroid on expression of the GHRH receptor (GHRH-R) gene in the
      rat pituitary in vivo and in pituitary cells in vitro. Adult male rats were
      adrenalectomized or sham operated and treated with s.c. implants of cholesterol
      or corticosterone. Adrenalectomized animals showed substantially reduced
      pituitary GHRH-R mRNA levels, when compared with untreated sham-operated animals.
      Conversely, administration of corticosterone increased pituitary GHRH-R mRNA
      levels in intact, as well as adrenalectomized rats. We also analyzed the effects
      of the synthetic glucocorticoid, dexamethasone, on GHRH-R mRNA expression in
      cultured rat anterior pituitary cells. GHRH-R mRNA was significantly increased by
      dexamethasone, with a maximal response observed in the presence of 100 nM
      hormone. This dose of dexamethasone substantially elevated GHRH-R mRNA after 6 h,
      12 h, and 24 h of treatment. Dexamethasone did not increase GHRH-R mRNA in the
      presence of the transcriptional inhibitor actinomycin D, indicating that the
      predominant effect of the hormone is to increase transcription of the GHRH-R
      gene. These data demonstrate that GHRH-R mRNA levels are directly stimulated by
      glucocorticoids, both in the presence and absence of hypothalamic influences,
      providing a probable explanation for the ability of this steroid to alter
      pituitary responsiveness to GHRH.

PMID- 9165037
TI  - Extracellular matrix regulates ovarian hormone-dependent proliferation of mouse
      mammary epithelial cells.
AB  - Mammary stromal cells can modulate steroid hormone responsiveness both in vivo
      and in vitro. One of the mechanisms by which stromal cells can influence
      epithelial cell behavior is by modifying the composition of the extracellular
      matrix (ECM). In this report, we have investigated the effects of five ECM
      molecules on control of epithelial cell proliferation by estrogen (E2) and
      progestin (R5020) under serum-free culture conditions. To assess the contribution
      of mammary gland differentiation in determining epithelial cell interactions with
      ECM, the behavior of mammary epithelial cells derived from nulliparous and
      pregnant mice was compared. We report the novel finding that the proliferative
      responses of mammary epithelial cells to progestin is influenced by specific ECM
      molecules. However, the primary determinant of hormonal responsiveness is the
      developmental state of the gland from which the epithelial cells were derived.
      Nulliparous-derived epithelial cells, proliferated in response to R5020 only on
      fibronectin (FN) and collagen IV (Col IV). The more highly differentiated,
      pregnancy-derived epithelial cells were not responsive to E2 or R5020 on any ECM.
      To determine if steroid hormone receptors were targets of ECM-mediated effects,
      ER and PR levels were analyzed. In both nulliparous and pregnancy-derived
      cultures, PR binding levels were maintained at similar levels on all ECMs.
      However, ER levels were not maintained in nulliparous-derived cultures, and this
      may have contributed to the lack of a significant response to E2. Alternatively
      or in addition, E2-induced responses may require additional signals or growth
      factors that are provided by stromal cells in vivo or by serum supplementation in
      vitro. These results demonstrate the ECM molecules, fibronectin and collagen IV,
      can modulate responsiveness of mammary epithelial cells to R5020 in vitro, and
      may be the mediators of stromal influences on hormone responsiveness in vivo.
      However, the specific effects of ECM and hormones are also determined by the
      developmental state of the mammary gland from which the cells are derived. Thus,
      mammary gland differentiation, ovarian hormones, and ECM composition may act in
      concert to determine the outcome of hormone treatment on cell proliferation.

PMID- 9165038
TI  - Insulin stimulates the phosphorylation of the 66- and 52-kilodalton Shc isoforms
      by distinct pathways.
AB  - In contrast to the 52-kDa Shc isoform, insulin stimulation caused a quantitative,
      time-dependent decrease in the SDS-PAGE mobility of 66-kDa Shc in both Chinese
      hamster ovary/IR cells and 3T3L1 adipocytes. Alkaline phosphatase treatment and
      direct phosphoamino acid analysis demonstrated that insulin stimulated an
      increase in serine phosphorylation of the 66-kDa isoform but not 52-kDa Shc,
      although the latter displayed a marked increase in tyrosine phosphorylation. To
      identify the responsible kinase pathway, we compared the effects on 66-kDa Shc
      serine phosphorylation by insulin, anisomycin, and osmotic shock, agents that
      specifically activate the ERK, JNK, or both pathways, respectively. Insulin and
      osmotic shock both stimulated a decrease in 66-kDa Shc mobility, whereas
      anisomycin had no effect. Furthermore, expression of a dominant-interfering Ras
      mutant (N17Ras) prevented the insulin-stimulated, but not the osmotic shock
      induced serine phosphorylation of 66-kDa Shc. Consistent with a MEK-dependent
      pathway mediating 66-kDa Shc serine phosphorylation, the specific MEK inhibitor
      (PD98059) and expression of a dominant-interfering MEK mutant partially inhibited
      both the insulin and osmotic shock-induced reduction in 66-kDa Shc mobility. In
      contrast, expression of the MAP kinase phosphatase (MKP-1) completely prevented
      ERK activation but did not inhibit the serine phosphorylation of 66-kDa Shc.
      These data demonstrate that insulin stimulates the serine phosphorylation of the
      66-kDa Shc isoform through a MEK-dependent mechanism.

PMID- 9165039
TI  - Cloning and functional expression of the luteinizing hormone receptor
      complementary deoxyribonucleic acid from the marmoset monkey testis: absence of
      sequences encoding exon 10 in other species.
AB  - Based on sequence homologies among the human, porcine, rat, and mouse genes for
      the LH receptor (LHR), overlapping partial fragments of LHR complementary DNAs
      (cDNAs) were multiplied from marmoset monkey testicular RNA using reverse
      transcription-PCR. Ligations of the individual cDNA fragments generated a full
      length monkey LHR cDNA (2031 bp) containing the complete amino acid-coding
      sequence (676 amino acids). Northern hybridization analysis of monkey testicular
      RNA, using a complementary RNA probe corresponding to the full-length cDNA,
      demonstrated major transcripts of 5.5 and 1.4 kilobases and minor ones of 4.0,
      2.7, and 1.9 kilobases. Sequence analysis of the monkey LHR cDNA revealed a
      striking feature, i.e. the absence of an 81-bp nucleotide sequence corresponding
      to exon 10, present in the LHR cDNAs of all other species studied to date. The
      monkey LHR cDNA displayed 83-94% overall sequence homology with the other
      mammalian LHR cDNAs. Reverse transcription-PCR with human exon 10-specific
      primers demonstrated the total absence of this sequence from the monkey LHR
      messenger RNA. Southern hybridization of monkey genomic DNA using a human exon 10
      probe demonstrated its presence in the monkey gene and that it is totally spliced
      out from the primary transcript. COS cells transfected with the monkey LHR cDNA
      showed similar high affinity (Kd = 0.25 nmol/liter) of [125I]iodo-hCG binding as
      those transfected with human LHR cDNA (Kd = 0.20 nmol/liter). The cells
      expressing the recombinant monkey and human LHR displayed similar responses of
      extracellular cAMP and inositol trisphosphate to hCG. In conclusion, marmoset
      monkey LHR seems to lack the sequence corresponding to exon 10 of the LHR gene in
      other mammalian species. The truncation does not alter LHR function, as the
      monkey receptor protein bound hCG and evoked cAMP and inositol trisphosphate
      responses comparable to those of the human LHR containing the exon 10-encoded
      structure. As the sequence homologous to exon 10 is missing in the other two
      glycoprotein receptors, i.e. those of FSH and TSH, this extra exon is apparently
      inserted into the LHR messenger RNA of some species during evolution from
      intronic sequences by a change in alternative splicing.

PMID- 9165040
TI  - Decidual/trophoblast prolactin-related protein: characterization of gene
      structure and cell-specific expression.
AB  - Decidual/trophoblast PRL-related protein (d/tPRP) is a member of the PRL gene
      family and is dually expressed in uterine and placental tissues in a highly
      coordinated pattern during pregnancy. In the present study, we describe the
      isolation and characterization of the d/tPRP gene. A lambda DASH II Wistar-Kyoto
      rat genomic library was screened with a labeled d/tPRP complementary DNA,
      resulting in the isolation of two phage clones, RGLd-41 [17.7 kilobases (kb)] and
      RGLd-42 (15.8 kb). RGLd-41 alone was found to contain the full-length d/tPRP gene
      and was used for subsequent analyses. The d/tPRP gene possesses a six-exon, five
      intron organization. Relative to other highly conserved members of the PRL gene
      family, d/tPRP contains a single small additional exon (exon 3) situated between
      exons 2 and 3 of the prototypical PRL gene. The region corresponding to exon 3 of
      d/tPRP encodes for a unique amino acid region found in a subset of PRL family
      members. A reverse transcription-PCR (RT-PCR) tissue survey for d/tPRP messenger
      RNA revealed that d/tPRP expression was restricted to decidual and trophoblast
      tissues. A single transcription start site 65 bp upstream of the initiation codon
      was identified in decidual tissue, whereas multiple transcription start sites
      ranging from 61-66 bp upstream of the initiation codon were detected in placental
      tissue. Various tissue culture systems (primary cultures and cell lines) were
      evaluated for d/tPRP expression and activation of a 3.96-kb d/tPRP promoter
      luciferase reporter construct. Decidual, spongiotrophoblast, and trophoblast
      giant cell populations expressed d/tPRP and were capable of activating the d/tPRP
      promoter-reporter construct, whereas other cell types were ineffective. Limited
      d/tPRP promoter activation was noted in uterine stromal cell lines. In summary,
      d/tPRP possesses a unique six-exon, five-intron gene structure and exhibits cell
      specific expression that is regulated at least in part by a 3.96-kb 5'-flanking
      region.

PMID- 9165041
TI  - Activation of the hexosamine pathway by glucosamine in vivo induces insulin
      resistance in multiple insulin sensitive tissues.
AB  - We determined the effect of infusion of glucosamine (GlcN), which bypasses the
      rate limiting reaction in the hexosamine pathway, on insulin-stimulated rates of
      glucose uptake and glycogen synthesis in vivo in rat tissues varying with respect
      to their glutamine:fructose-6-phosphate amidotransferase (GFA) activity. Three
      groups of conscious fasted rats received 6-h infusions of either saline (BAS),
      insulin (18 mU/kg x min) and saline (INS), or insulin and GlcN (30 micromol/ kg x
      min, GLCN). [3-(3)H]glucose was infused to trace whole body glucose kinetics and
      glycogen synthesis, and rates of tissue glucose uptake were determined using a
      bolus injection of [1-(14)C]2-deoxyglucose at 315 min. GlcN decreased insulin
      stimulated glucose uptake (315-360 min) by 49% (P < 0.001) at the level of the
      whole body, and by 31-53% (P < 0.05 or less) in the heart, epididymal fat,
      submandibular gland and in soleus, abdominis and gastrocnemius muscles. GlcN
      completely abolished glycogen synthesis in the liver. GlcN decreased insulin
      stimulated glucose uptake similarly in the submandibular gland (1.3 +/- 0.2 vs.
      2.0 +/- 0.3 nmol/mg protein x min, GLCN vs. INS, P < 0.05) and gastrocnemius
      muscle (1.4 +/- 0.3 vs. 3.1 +/- 0.5 nmol/mg protein x min), although the activity
      of the hexosamine pathway, as judged from basal GFA activity, was 10-fold higher
      in the submandibular gland (286 +/- 35 pmol/mg protein x min) than in
      gastrocnemius muscle (27 +/- 3 pmol/mg protein x min, P < 0.001). These data
      raise the possibility that overactivity of the hexosamine pathway may contribute
      to glucose toxicity not only in skeletal muscle but also in other insulin
      sensitive tissues. They also imply that the magnitude of insulin resistance
      induced between tissues is determined by factors other than GFA.

PMID- 9165042
TI  - Expression of adrenomedullin (ADM) and its binding sites in the rat uterus:
      increased number of binding sites and ADM messenger ribonucleic acid in 20-day
      pregnant rats compared with nonpregnant rats.
AB  - RIA of nonpregnant rat uterus extracts showed 0.68 +/- 0.08 pmol/g adrenomedullin
      (ADM) and 3.23 +/- 0.08 pmol/g calcitonin gene-related peptide (CGRP). In the
      pregnant (20 days gestation) uterus, the ADM content was 0.90 +/- 0.17 pmol/g,
      and CGRP could not be detected. ADM messenger RNA was detected at high levels in
      the uterus, with a 1.8-fold increase in expression in pregnancy.
      Pharmacologically distinct binding sites for ADM (Bmax = 21 +/- 2 fmol/mg
      protein, dissociation constant = 80 +/- 6 pM), and CGRP (Bmax = 101 +/- 18
      fmol/mg protein, dissociation constant = 140 +/- 20 pM) were identified in
      nonpregnant uterus. Competition for 125I[Tyr0]alphaCGRP binding was shown by both
      ADM and CGRP (8-37), whereas CGRP and CGRP (8-37) did not compete for 125I-ADM
      binding sites. The density of the ADM-binding sites was 10 times greater in
      pregnant uterus (Bmax = 211 +/- 39 fmol/mg protein, P < 0.01) than nonpregnant
      uterus. CGRP receptor messenger RNA was identified in both nonpregnant and
      pregnant uteri. In isolated nonpregnant rat uteri, CGRP and ADM attenuated the
      contractile response to galanin by 77 +/- 10% and 57 +/- 10%, respectively. The
      responses to both CGRP and ADM were abolished by CGRP (8-37). These results
      demonstrate, for the first time, the presence of ADM and specific binding sites
      for both ADM and CGRP in the rat uterus.

PMID- 9165043
TI  - Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive
      intestinal peptide (VIP) stimulate interleukin-6 production through the third
      subtype of PACAP/VIP receptor in rat bone marrow-derived stromal cells.
AB  - Regulation of Interleukin-6 (IL-6) production in bone marrow (BM)-derived stromal
      cells by neuropeptides, pituitary adenylate cyclase activating polypeptide
      (PACAP) and vasoactive intestinal peptide (VIP), was examined. Both forms of
      PACAP, PACAP-27 and PACAP-38, as well as VIP significantly increased IL-6
      production by rat BM-derived stromal cells at physiological concentrations
      ranging from 10(-10)-10(-8) M. The three related peptides (PACAP-27, -38, and
      VIP) stimulated the production of both cAMP and inositol 1,4,5-trisphosphate
      (IP3) in rat BM-derived stromal cells with similar 50% effective concentrations.
      The stimulatory potency of the three related peptides for the production of IL-6,
      cAMP, and IP3 was almost consistent, suggesting that the dual signaling
      transduction pathways may be involved in PACAP/VIP-induced IL-6 production in rat
      BM-derived stromal cells. The messenger RNA (mRNA) for the third subtype of PACAP
      receptor (PVR3) was found to be abundantly expressed in both BM-derived stromal
      cells and the BM tissue, whereas little of the mRNA for type 1 (PVR1) nor type 2
      (PVR2) was detected. Furthermore, the mRNAs for PACAP and VIP were detected in
      the BM tissue, suggesting that both PACAP/VIP and PVR3 are synthesized in vivo in
      the BM. The results shown in this paper suggest that PACAP/VIP and their receptor
      play an important role in the IL-6 production and perhaps in the hematopoiesis in
      the BM.

PMID- 9165044
TI  - Cyclic adenosine 3',5'-monophosphate regulates GLUT4 and GLUT1 glucose
      transporter expression and stimulates transcriptional activity of the GLUT1
      promoter in muscle cells.
AB  - We have previously reported that innervation-dependent basal contractile activity
      regulates in an inverse manner the expression of GLUT1 and GLUT4 glucose
      transporters in skeletal muscle. Based on the facts that muscle innervation
      decreases and muscle denervation increases cAMP levels, we investigated whether
      cAMP might mediate the effects of innervation/denervation on glucose transporter
      expression. Treatment of L6E9 myotubes with 8-bromo-cAMP, forskolin, or
      monobutyryl-8-bromo-cAMP led to a marked decrease in GLUT4 protein levels; 8
      bromo-cAMP also diminished GLUT4 messenger RNA (mRNA), suggesting
      pretranslational repression. In contrast, L6E9 myoblasts and myotubes responded
      to 8-bromo-cAMP or forskolin by increasing the cell content of GLUT1 protein.
      Induction of GLUT1 protein was a consequence of the activation of different
      mechanisms in myoblast and myotube cells; whereas 8-bromo-cAMP treatment caused a
      substantial increase in GLUT1 mRNA in myoblasts, no change in GLUT1 mRNA was
      detected in myotubes. The increase in GLUT1 mRNA in L6E9 myoblasts induced by 8
      bromo-cAMP was the result of transcriptional activation, as concluded from
      transfection analysis of 2.1 kilobases of the rat GLUT1 gene promoter fused to
      the bacterial chloramphenicol acetyltransferase gene. Furthermore, the
      stimulatory effect of 8-bromo-cAMP on the transcriptional activity of the GLUT1
      promoter required a 33-bp sequence lying 5' upstream of the transcription start
      site. In all, cAMP inversely regulates GLUT4 and GLUT1 glucose transporter
      expression in muscle cells. Furthermore, our results suggest that down-regulation
      of GLUT4 expression and up-regulation of GLUT1 expression in muscle associated
      with denervation are partly attributable to cAMP.

PMID- 9165045
TI  - Angiotensin-responsive adrenal glomerulosa cell proteins: characterization by
      protease mapping, species comparison, and specific angiotensin receptor
      antagonists.
AB  - Angiotensin II (AngII)-stimulated aldosterone synthesis is mediated by the AngII
      type 1 (AT1) receptor and requires ongoing protein synthesis. Hormonally
      stimulated turnover of a family of 28- to 30-kDa proteins (p30, or steroidogenic
      acute regulatory proteins) has been linked to enhanced steroid synthesis in
      several tissues. Our previous work showed that AngII, dibutyryl cAMP, potassium,
      and atrial natriuretic peptide affected labeling of a group of eight proteins
      (four of 28 kDa and four of 30 kDa) in bovine adrenal glomerulosa cells. This
      report extends our findings in three ways: 1) The eight [35S]-methionine-labeled
      p30 proteins in bovine cells were compared with each other by chymotryptic
      peptide mapping. Similarity in maps indicated that the eight proteins share a
      common primary structure. 2) Dibutyryl cAMP treatment of rat adrenal glomerulosa
      cells affected the levels of four 28-kDa proteins and one 35-kDa protein, whereas
      AngII affected two of the 28-kDa proteins. There were no responsive 30-kDa
      proteins in rats comparable with those seen in bovine cells. These results
      indicate a species difference in the affected proteins. 3) The AT1 receptor
      antagonist, losartan, inhibited the effects of AngII on aldosterone synthesis and
      turnover of the p30 proteins in bovine adrenal glomerulosa cells. PD123319, an
      antagonist specific for the AngII type 2 receptor, did not block AngII-stimulated
      aldosterone synthesis and had much less effect on p30 protein labeling than did
      losartan. These results add to the growing body of evidence that this family of
      p30 or steroidogenic acute regulatory proteins plays a role in the acute
      regulation of steroidogenesis by a wide variety of stimulatory hormones in
      several tissues and species. In addition, losartan's inhibition of AngII's
      effects on the p30 proteins is consistent with a key role for these proteins in
      processes linking occupation of the AT1 receptor to stimulation of aldosterone
      synthesis.

PMID- 9165046
TI  - Determinants of specificity of transactivation by the mineralocorticoid or
      glucocorticoid receptor.
AB  - Glucocorticoids and mineralocorticoids have distinct in vivo roles despite close
      structural homology and similarities in vitro. Known mechanisms of specificity
      focus on factors extrinsic to the receptor; interactions that directly regulate
      the receptor to confer specificity are less well understood, particularly for the
      mineralocorticoid receptor (MR). To examine relative MR vs. glucocorticoid
      receptor (GR) function in a more physiological context, we compared
      transactivation by GR and MR in the standard experimental fibroblast CV-1 cell
      line, the renal epithelial LLC-PK1 line, and neuronal medullary raphe RN33B
      cells. Maximal transactivational activity mediated by MR, relative to that
      mediated by GR, is enhanced in both of these cell lines and is primarily
      conferred by an N-terminal-mediated enhancement of the MR response. In addition,
      the ligand concentration required for maximal transcriptional activity of the GR
      varies significantly between cell lines. This is independent of binding affinity
      or 11beta-hydroxysteroid dehydrogenase-mediated inactivation and may contribute
      to in vivo tissue-specific differences in responses to the GR. Although ligand
      binding affinity is clearly conferred by the LBD, receptor-specific variations
      between cell lines in transcriptional sensitivity to ligand appear, rather, to be
      associated with the N-terminus. These studies demonstrate that the specificity of
      the MR vs. the GR response may be mediated via unique cellular factors, as well
      as suggesting a novel means of expanding the cellular response to cortisol.

PMID- 9165047
TI  - Regulation of follistatin production by rat granulosa cells in vitro.
AB  - The aims of this study were to apply enzyme-linked immunosorbent assays (ELISA)
      for human follistatins (FS) to measure total immunoreactive (ir-) rat FS and free
      rat FS, and investigate the regulation of production of total ir-FS and free FS
      by rat granulosa cells (GC) in vitro. Production of ir-inhibin was monitored as
      an index of GC function. The ELISAs for total ir-FS, based on an
      immunoradiometric assay developed recently for human FS, and free FS, based on
      capture of FS by a monoclonal antibody and detection by activin A binding, had
      sensitivities of 0.4 and 0.8 ng recombinant human (rh-) FS 288/ml, respectively,
      and did not cross-react with inhibin A, rLH, or FSH. rh-Activin did not cross
      react in the total ir-FS ELISA, but interfered with the measurement of free FS.
      Dilutions of GC-conditioned medium were parallel to the standard curve of rh-FS
      288 for each assay. The values obtained in the free FS assay were 10- to 20-fold
      higher than those in the total ir-FS ELISA, suggesting that rat FS may be
      recognized by the antibodies differently than the human standard. Both total ir
      FS and free FS production by undifferentiated GC from diethylstilbestrol (DES)
      treated, immature rats increased with cell number and time in culture and were
      stimulated dose dependently by FSH, rh-activin A (except free FS, which was not
      measured because of interference), forskolin, and phorbol 12-myristrate. The
      effects of FSH and activin on FS production by undifferentiated GC were additive.
      There were significant effects of degree of differentiation of GC on basal FS
      production and responsiveness to FSH, LH, and rh-activin A. Both total ir-FS and
      free basal FS production increased up to 4-fold with the degree of
      differentiation of GC, produced by treating rats in vivo with DES
      (undifferentiated), DES plus FSH (partially differentiated), or DES plus FSH plus
      hCG (fully differentiated). The addition of FSH in vitro increased FS production
      by undifferentiated and partially differentiated GC, but not by fully
      differentiated GC. The only detectable effect of LH on FS production was on
      partially differentiated GC. Activin A stimulated total ir-FS production by
      undifferentiated and partially differentiated GC, but inhibited total ir-FS
      production by fully differentiated GC. Ir-inhibin production in these experiments
      was similar to that of FS with the following exceptions; phorbol 12-myristrate
      inhibited ir-inhibin production by undifferentiated GC, basal ir-inhibin
      decreased in fully differentiated GC, FSH stimulated ir-inhibin only in
      undifferentiated GC, and rh-activin A stimulated ir-inhibin at all stages. It is
      concluded that 1) FS protein production by cultured undifferentiated rat GC is up
      regulated by FSH and activin, possibly via both protein kinase A and C pathways;
      2) increasing GC differentiation is associated with a significant increase in
      basal FS production by rat GC and a change in the hormonal regulation of FS
      production; and 3) FS and ir-inhibin production by cultured rat GC can be
      differentially regulated. The results are consistent with the hypothesis that
      activin tone decreases within follicles as they develop due to increased
      production of the activin-binding protein FS.

PMID- 9165048
TI  - Mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways are
      not sufficient for insulin-like growth factor I-induced mitogenesis and
      tumorigenesis.
AB  - Insulin-like growth factor-I (IGF-I) and insulin are known to activate a
      signaling cascade involving ras --> kappa raf-1 --> mitogen-activated protein
      (MAP) kinase kinase (MEK) --> p42/p44 MAP kinase (Erk-1 and -2). Recent reports
      suggest that activation of this ras/MAP kinase pathway is involved in mitogenesis
      and c-fos transcription but is not required for insulin action on metabolic
      processes such as glycogen synthesis, lipogenesis, and GLUT-4-mediated glucose
      transport. Previously we and others have demonstrated that substitution of both
      tyrosines at positions 1250 and 1251 in the carboxy-terminal region of the human
      IGF-I receptor has relatively small effects on receptor and endogenous substrate
      phosphorylation but completely abrogated the ability of these cells to form
      tumors in nude mice or proliferate in response to IGF-I in culture. Replacement
      of the tyrosine at position 1316 also did not affect the kinase activity of the
      receptor with respect to autophosphorylation or phosphorylation of endogenous
      substrates but did reduce the ability of the receptor to mediate mitogenic or
      tumorigenic signals. To further characterize the role of these tyrosines in IGF-I
      receptor function, we have used three distinct approaches to examine the ras/MAP
      kinase pathway in IGF-I-induced mitogenesis and tumorigenesis in NIH-3T3 cells
      overexpressing wild-type and mutated IGF-I receptors: 1) tyrosine phosphorylation
      of the MAP kinases Erk-1 and -2; 2), mobility shifts indicative of MAP kinase
      phosphorylation; and 3) in vitro MAP kinase activation. We have also examined IGF
      I-induced phosphatidylinositol (PI) 3-kinase activation in the same cell lines.
      By each method we show that the IGF-I-induced MAP kinase
      phosphorylation/activation and PI 3-kinase activation, are not different between
      cells overexpressing wild-type IGF-I receptors and cells carrying IGF-I receptors
      having tyrosine motifs replaced at positions 1250 and 1251. We conclude that
      mitogenic and tumorigenic signals involving tyrosine residues in the C-terminal
      domain of the IGF-I-receptor include pathways other than the MAP kinase and PI 3
      kinase pathways.

PMID- 9165049
TI  - Regulation of iodothyronine deiodinase activity as studied in thyroidectomized
      rats infused with thyroxine or triiodothyronine.
AB  - To provide new insights into the in vivo regulation of iodothyronine deiodinases
      in the different tissues of the rat, we have evaluated the effects on these
      enzymatic activities of T4 or T3 infusions into thyroidectomized rats.
      Thyroidectomized rats were infused with placebo, T4, or T3. Placebo-infused
      intact rats served as euthyroid controls. Plasma and samples of cerebral cortex,
      brown adipose tissue, pituitary, liver, and lung were obtained after 12-13 days
      of infusion. Plasma TSH, plasma and tissue T4 and T3, and iodothyronine
      deiodinase activities were determined. Type II 5'-deiodinase (DII) was increased
      in cortex, brown adipose tissue, and pituitary from animals infused with placebo.
      DII activity returned to normal only with T4 infusion, remaining elevated in the
      animals infused with T3 alone despite normal tissue T3 concentrations. Cortex
      type III 5-deiodinase was only increased when hyperthyroidism was induced by
      infusion of T3. Liver type I 5'-deiodinase (DI) paralleled the changes in plasma
      and tissue T3 regardless of whether T4 or T3 was infused. On the contrary, the
      increase in lung DI, proportional to the increases in plasma and tissue T3, was
      higher when T4 was infused. As a rule, the tissues with DII presented a tighter
      homeostasis in their T3 concentrations than the tissues with DI. In conclusion,
      the regulation of iodothyronine deiodinases depends on the hormone infused into
      the thyroidectomized animals and on the tissue in which the deiodinase is
      studied, demonstrating the existence of tissue-specific regulation of its thyroid
      hormone concentrations.

PMID- 9165050
TI  - Leptin prevents fasting-induced suppression of prothyrotropin-releasing hormone
      messenger ribonucleic acid in neurons of the hypothalamic paraventricular
      nucleus.
AB  - Prolonged fasting is associated with a number of changes in the thyroid axis
      manifested by low serum T3 and T4 levels and, paradoxically, low or normal TSH.
      This response is, at least partly, caused by suppression of proTRH gene
      expression in neurons of the hypothalamic paraventricular nucleus (PVN) and
      reduced hypothalamic TRH release. Because the fall in thyroid hormone levels can
      be blunted in mice by the systemic administration of leptin, we raised the
      possibility that leptin may have an important role in the neuroendocrine
      regulation of the thyroid axis, through effects on hypophysiotropic neurons
      producing proTRH. Adult male, Sprague-Dawley rats were either fed normally,
      fasted for 3 days, or fasted and administered leptin at a dose of 0.5 microg/gm
      BW i.p. every 6 h. Fasted animals showed significant reduction in plasma total
      and free T4 and T3 levels compared with controls, that were restored toward
      normal by the administration of leptin. Percent free T4, but not percent free T3,
      increased during fasting, further suggesting a reduction in plasma transthyretin
      levels that did not return to fed levels after leptin administration. By
      semiquantitative analysis of in situ hybridization autoradiograms, proTRH
      messenger RNA in medial parvocellular PVN neurons was markedly suppressed in the
      fasting animals but was restored to normal by leptin administration [fed vs. fast
      vs. fast/leptin (density units x 10(8)): 8.5 +/- 0.4, 3.2 +/- 0.2, 8.1 +/- 0.8].
      In contrast, proTRH messenger RNA in adjacent neurons in the lateral hypothalamus
      that do not have a hypophysiotropic function remained unchanged by any of the
      experimental manipulations. These findings indicate that leptin has a selective,
      central action to modulate the hypothalamic-pituitary-thyroid axis by regulating
      proTRH gene expression in the PVN but does not have peripheral effects on thyroid
      binding proteins. We propose that the fall in circulating leptin levels during
      fasting resets the set point for feedback inhibition by thyroid hormones on the
      biosynthesis of hypophysiotropic proTRH, thereby allowing adaptation to
      starvation.

PMID- 9165052
TI  - Effects of photoperiod on estrogen receptor, tyrosine hydroxylase, neuropeptide
      Y, and beta-endorphin immunoreactivity in the ewe hypothalamus.
AB  - The neural components underlying the influence of photoperiod upon reproductive
      functioning are poorly understood. In this study, we have used
      immunocytochemistry to examine whether changes in photoperiod may influence
      specific neuronal cell populations implicated in mediating gonadal steroid
      feedback actions on GnRH neurons. Short day (SD) exposed ewes in the midluteal
      stage of the estrous cycle and long day (LD) anestrous ewes were perfused in
      pairs and hypothalamic brain sections immunostained for tyrosine hydroxylase
      (TH), neuropeptide Y (NPY), beta-endorphin (betaE), and the estrogen receptor
      (ER). The number of ER-immunoreactive cells detected within the preoptic area,
      but not the hypothalamus, was approximately 20% higher (P < 0.05) in LD ewes
      compared with SD animals. The numbers of TH-immunoreactive neurons comprising the
      A12, A14, and A15 cell groups were not different between LD and SD ewes, and the
      percentage of A12 (approximately 15%) and A14 (approximately 25%) neurons
      expressing ERs was similarly unaffected by photoperiod. The number of betaE
      neurons detected in the arcuate nucleus was 50% lower (P < 0.05) in SD vs. LD
      ewes, whereas NPY-immunoreactive cell numbers in the median eminence were 300%
      higher (P < 0.05). Approximately 3% of NPY neurons in the median eminence, and
      10% in the arcuate nucleus, expressed ER immunoreactivity in a photoperiod
      independent manner. These studies indicate that changes in photoperiod may
      regulate ER expression within the preoptic area and suggest that hypothalamic NPY
      and betaE neurons are involved in the seasonal regulation of reproductive
      activity in the ewe.

PMID- 9165051
TI  - Insulinoma cells contain an isoform of Ca2+/calmodulin-dependent protein kinase
      II delta associated with insulin secretion vesicles.
AB  - The Ca2+/calmodulin dependent protein kinase II (CaM kinase II) is thought to
      play an important part in glucose-stimulated insulin secretion. To determine
      which of the known subtypes (alpha, beta, gamma, delta) occur in insulin
      secreting cells, we amplified all types of CaM kinase II by RT-PCR and found the
      beta3-, gamma-, delta2- and delta6-subtypes in RINm5F insulinoma cells. None of
      the other 8 delta-subtypes was present. Antibodies generated against the
      bacterially expressed association domain of the delta2-subtype recognized the
      recombinant gamma and delta-subtypes. In INS-1 and RINm5F cells, as well as
      freshly isolated rat islets, only a 55-kDa protein corresponding in size to the
      delta2-subtype expressed in NIH3T3 fibroblasts was detected. The delta2-subtype
      therefore appears to represent the predominant subtype of CaM kinase II present
      in insulin secreting cells. The enzyme was primarily associated with cytoskeletal
      structures, and very little was present in the soluble compartment or detergent
      soluble fraction in INS-1- or RINm5F-cells. An analysis of its subcellular
      distribution was performed by sucrose and Nycodenz density gradient fractionation
      of INS-1 cells and detection of CaM kinase II delta by immune blots. The enzyme
      codistributed with insulin used as a marker for secretory granules but not with
      the lighter synaptic-like microvesicles detected with an antibody against
      synaptophysin, plasma membranes (syntaxin 1), lysosomes (arylsulfatase), or
      mitochondria (cytochrome c oxidase). CaM kinase II delta2 thus is identified as
      the subtype associated with insulin secretory granules and is likely to be
      involved in insulin secretion.

PMID- 9165053
TI  - In vivo regulation of chromogranin A messenger ribonucleic acid in the
      parathyroid by 1,25-dihydroxyvitamin D: studies in normal rats and in chronic
      renal insufficiency.
AB  - Chromogranin-A (CgA) and PTH are the two major secretory products of the
      parathyroid gland. In vitro, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] increases
      CgA, but decreases PTH messenger RNA (mRNA) levels. We investigated the
      physiological significance of the induced changes in CgA expression by examining
      the effects of 1,25-(OH)2D3 on parathyroid CgA mRNA levels in vivo. Normal rats
      were injected with 1,25-(OH)2D3 at 48 and 24 h before blood sampling and
      isolation of both parathyroid glands. Parathyroid total RNA was extracted and CgA
      and PTH mRNA quantified by Northern blot analysis. CgA mRNA levels increased 1.6
      , 3.2- and 5.6-fold, whereas PTH mRNA levels decreased by 37, 63 and 97%,
      respectively, with 1,25-(OH)2D3 doses of 10, 50, and 250 pmol/100 g BW.
      Parathyroid gland CgA expression also was examined in rats with mild chronic
      renal insufficiency, induced by a 5/6 nephrectomy 5 weeks earlier. Chronic renal
      insufficiency rats, fed normal chow, had elevated serum urea, creatinine, and PTH
      levels and reduced 1,25-(OH)2D3 but normal serum levels of calcium and phosphate.
      PTH mRNA levels were elevated 4-fold and CgA mRNA levels were 50% lower in the
      uremic animals. This indicates that the regulation of CgA expression in
      normocalcemic rats occurs at physiological 1,25-(OH)2D3 concentrations. In
      summary, increases and decreases in serum 1,25-(OH)2D3 levels are associated with
      corresponding increases and decreases in CgA mRNA levels in the parathyroid
      glands of rats. Therefore, this study is the first to demonstrate the
      physiological relevance of the earlier in vitro observations.

PMID- 9165054
TI  - Interaction between adrenaline and epidermal growth factor in the control of
      liver glycogenolysis in mouse.
AB  - Epidermal growth factor (EGF) stimulates glycogenolysis in mouse liver, but the
      effect requires concentrations that are only achieved in plasma upon adrenergic
      stimulation of EGF release from submandibular salivary glands. Thus, we studied
      the interaction between adrenaline and EGF in liver glycogen metabolism, both in
      whole animals and in isolated hepatocytes. Adrenaline administered to
      anesthetized mice stimulated both the endocrine secretion of EGF from
      submandibular salivary glands and the degradation of glycogen in the liver. In
      sialoadenalectomized mice, adrenaline administration did not increase plasma EGF
      concentration. In these animals, the glycogenolytic response to adrenaline was
      enhanced. The sensitivity of hepatocytes to adrenaline was similar in cells from
      sialoadenalectomized and sham-operated mice. EGF, added to isolated hepatocytes,
      reduced the glycogenolytic effect of adrenaline (the maximal effect but not the
      ED50). Adrenaline stimulated glycogen degradation through both an alpha1
      adrenergic mediated Ca2+ increase and a beta-adrenergic-mediated cAMP increase.
      EGF did not interfere with the rise of cytosolic Ca2+ but decreased the cAMP
      signal. EGF did not decrease the glycogenolytic effect of phenylephrine or VP
      (which increased cytosolic Ca2+ but not cAMP), but EGF decreased both the
      glycogenolytic effect and the cAMP signal generated by glucagon or forskolin. EGF
      did not interfere with the glycogenolytic effect of CPT-cAMP or bt2-cAMP. The
      effect of EGF on cAMP was blocked by 3-isobutyl-1-methylxanthine. These results
      demonstrate that the effect of EGF on the glycogenolytic action of adrenaline
      involves interference with the generation of the cAMP signal. We suggest that EGF
      induces such an effect through the activation of a phosphodiesterase.

PMID- 9165055
TI  - Cytokines induce deoxyribonucleic acid strand breaks and apoptosis in human
      pancreatic islet cells.
AB  - We have previously observed that a 6-day exposure of human pancreatic islets to a
      combination of cytokines (interleukin-1beta 50 U/ml + tumour necrosis factor
      alpha 1000 U/ml + interferon-gamma 1000 U/ml) severely impairs beta-cell
      functions. In the present study, we examined whether this condition affects DNA
      integrity and viability of human islet cells. Cells were studied after 3, 6, and
      9 days of cytokine treatment by both single cell gel electrophoresis (the "comet
      assay," a sensitive method for detection of DNA strand breaks) and by a
      cytotoxicity assay using the DNA binding dyes Hoechst 33342 and propidium iodide
      as indices for the number of viable, necrotic, and apoptotic cells. Cytokine
      treatment for 6 and 9 days resulted in a 50% increase in comet length (P < 0.01
      vs. controls), indicating DNA strand breaks, as well as in a significant increase
      in the number of apoptotic cells (P < 0.02 vs. controls), but not in the number
      of necrotic cells. The arginine analogs N(G)-nitro-L-arginine and N(G)-monomethyl
      L-arginine prevented nitric oxide formation by the cytokines but did not
      interfere with cytokine-induced DNA strand breaks and apoptosis. The present data
      suggest that prolonged (6-9 days) exposure of human pancreatic islets to a
      mixture of cytokines induces DNA strand breaks and cell death by apoptosis. These
      deleterious effects of cytokines appear to be independent of nitric oxide
      generation.

PMID- 9165056
TI  - Adrenomedullin as an autocrine/paracrine apoptosis survival factor for rat
      endothelial cells.
AB  - Adrenomedullin is a potent vasorelaxant/hypotensive peptide recently isolated
      from human pheochromocytoma. We demonstrate here a novel role of this peptide as
      an apoptosis survival factor for rat endothelial cells. When rendered quiescent
      by serum deprivation, a fraction of endothelial cell cultures showed
      morphological and biochemical features characteristic of apoptosis.
      Adrenomedullin significantly suppressed apoptosis without inducing cell
      proliferation. Rat endothelial cells that contained high affinity binding sites
      for adrenomedullin expressed adrenomedullin gene and released the peptide into
      culture media. Addition of preimmune rabbit serum prevented apoptosis, whereas
      rabbit antiadrenomedullin antiserum partially, but significantly, abrogated the
      protective effect of the preimmune serum, suggesting its autocrine/paracrine
      role. Although adrenomedullin induced intracellular cAMP formation, other cAMP
      elevating agonists, such as prostaglandin I2 and forskolin, did not affect
      apoptosis. Furthermore, adenosine 3',5'-cyclicmonophosphothioate Rp-isomer, a
      cAMP antagonist, did not block the cell survival effect of adrenomedullin.
      Adrenomedullin neither increased intracellular Ca2+ concentrations nor inositol
      1,4,5-trisphosphate levels in rat endothelial cells. These results demonstrate
      that adrenomedullin suppresses serum deprivation-induced apoptosis of rat
      endothelial cells via cAMP-independent mechanism.

PMID- 9165057
TI  - Two proximal activating protein-1-binding sites are sufficient to stimulate
      transcription of the ovine follicle-stimulating hormone-beta gene.
AB  - FSH is an important regulator of mammalian gametogenesis and the female
      reproductive cycle. Although little is known about the transcriptional regulation
      of the beta-subunit (the rate-limiting subunit of FSH synthesis), sequence
      analysis of the ovine FSHbeta promoter has revealed a number of potential
      activating protein-1 (AP-1; Jun/Fos)-binding sites. To determine whether the gene
      encoding the beta-subunit of ovine FSH (oFSHbeta) is responsive to AP-1
      transcriptional complexes, chimeric constructs containing deleted portions of the
      oFSHbeta promoter fused to a luciferase reporter were transiently transfected
      along with c-Jun and c-Fos expression constructs into JAR cells. Analysis of
      these deletion constructs revealed that the proximal promoter of oFSHbeta is
      highly stimulated by c-Jun and c-Fos proteins (typically 20-fold with a reporter
      construct containing oFSHbeta sequences from -215 to +759 bp). This stimulation
      was lost when a similar construct containing sequences from -84 to +759 bp was
      tested. Transcriptional start site analysis using reverse transcription-PCR
      verified that the transcriptional initiation of the -215-bp deletion construct,
      with or without cotransfected c-Jun/c-Fos, was the same as that observed in vivo.
      Computer analysis of oFSHbeta sequences from -215 to +1 bp identified four
      putative AP-1-like elements, located at -155, -120, -83, and -10 bp. Gel
      retardation experiments using oligonucleotides corresponding to the four putative
      AP-1-like sites revealed that only -120 and -83 sites in oFSHbeta bound AP-1
      proteins in vitro. Site-directed mutagenesis of the -120 and -83 sites showed
      that each element was required for stimulation by c-Jun and c-Fos proteins as
      well as 12-O-tetradecanoyl phorbol-13-acetate in transient transfection assays.
      Finally, immunocytochemical dual labeling was used to show that more than 75% of
      all FSHbeta-containing cells in ovine pituitary sections from cycling ewes
      contained nuclear c-Jun, JunB, JunD, and Fos proteins. These data, taken
      together, show that oFSHbeta transcription can be stimulated by c-Jun and c-Fos
      proteins via two functionally linked AP-1-like sites in the oFSHbeta proximal
      promoter and that these sites are likely to be important regulators of FSH
      production in vivo.

PMID- 9165058
TI  - Immunohistochemical localization of somatostatin receptor SST2A in the rat
      pancreas.
AB  - Somatostatin (SRIF) acts on specific membrane receptors to inhibit exocrine and
      endocrine pancreatic functions. Five SRIF receptor genes have been cloned,
      producing six receptor proteins (sst-s). We used a recently developed antibody to
      localize the sst2A splice variant in the rat pancreas. Western blots identified
      the sst2A receptor as an 90 kDa glycosylated protein in pancreatic tissue. In
      tyramide-amplified immunostainings all acinar cells, and the glucagon and
      pancreatic polypeptide immunoreactive cells (A and PP, respectively) were
      intensely labeled for sst2A, while no signal was detected in SRIF producing (D)
      cells. A very few insulin immunoreactive (B) cells were also labeled for sst2A,
      but the signal in these cells was lower than in exocrine, A or PP cells.
      Absorption of the sst2A antibody with the receptor peptide abolished specific
      staining in both immunoblots and tissue sections (negative control). These
      studies are the first to localize any SRIF receptor subtype in the rat pancreas.
      The specific localization of sst2A receptor in acinar, A and PP cells if
      confirmed in humans, would suggest that subtype specific analogs will be useful
      for the therapeutic regulation of exocrine and/or endocrine pancreatic secretion.

PMID- 9165059
TI  - Adrenomedullin gene expression in the rat heart is stimulated by acute pressure
      overload: blunted effect in experimental hypertension.
AB  - The levels of adrenomedullin (ADM), a newly discovered vasodilating and
      natriuretic peptide, are elevated in plasma and ventricular myocardium in human
      congestive heart failure suggesting that cardiac synthesis may contribute to the
      plasma concentrations of ADM. To examine the time course of induction and
      mechanisms regulating cardiac ADM gene expression, we determined the effect of
      acute and short-term cardiac overload on ventricular ADM mRNA and immunoreactive
      ADM (ir-ADM) levels in conscious rats. Acute pressure overload was produced by
      infusion of arginine8-vasopressin (AVP, 0.05 microg/kg/min, i.v.) for 2 h into 12
      week-old hypertensive TGR(mREN-2)27 rats and normotensive Sprague-Dawley (SD)
      rats. Hypertension and marked left ventricular hypertrophy were associated with
      2.2-times higher ir-ADM levels in the left ventricular epicardial layer (178 +/-
      36 vs. 81 +/- 23 fmol/g, P<0.05) and 2.6-times higher ir-ADM levels in the left
      ventricular endocardial layer (213 +/- 23 vs. 83 +/- 22 fmol/g, P<0.01). The
      infusion of AVP for 2 h in normotensive rats produced rapid increases in the
      levels of left ventricular ADM mRNA (epicardial layer: 1.6-fold, P<0.05) and ir
      ADM (endocardial layer: from 83 +/- 22 to 140 +/- 12 fmol/g, P<0.05), whereas
      ventricular ADM mRNA and ir-ADM levels did not change significantly in
      hypertensive rats. Short-term cardiac overload, induced by administration of
      angiotensin II (33.3 microg/kg/h, s.c., osmotic minipumps) for two weeks in
      normotensive SD rats resulted in left ventricular hypertrophy (3.05 +/- 0.17 vs.
      2.75 +/- 0.3 mg/g, P<0.05) and a 1.5-fold increase (P<0.05) in ventricular ADM
      mRNA levels. In conclusion, the present results show that pressure overload
      acutely stimulated ventricular ADM gene expression in conscious normotensive rats
      suggesting a potential beneficial role for endogenous ADM production in the heart
      against cardiac overload. Since pressure overload-induced increase in ADM
      synthesis was attenuated in hypertensive rats, alterations in the ADM system may
      contribute to the pathogenesis of hypertension in the TGR(mREN-2)27 rat.

PMID- 9165060
TI  - Localization of the domains involved in ligand binding and activation of the
      glucose-dependent insulinotropic polypeptide receptor.
AB  - The receptors for the two structurally related insulinotropic hormones Glucose
      dependent Insulinotropic Polypeptide (GIP) and Glucagon-Like Peptide-1 (GLP-1)
      share approximately 40% sequence identity and demonstrate complete specificity
      for their endogenous ligands, while utilizing similar second messenger pathways.
      In the current study chimeric GIP-GLP-1 receptors were prepared, and the effect
      of domain-exchange on ligand binding and adenylyl cyclase activation examined. A
      chimera (CH-2) consisting of the first 132 amino acids of the external N-terminal
      (NT) domain bound 125I-GIP with high affinity (27.77 +/- 11.85 nM). However, for
      receptor coupling to cAMP production it was necessary to extend the NT into the
      first transmembrane (TM-1) region (CH-3: IC50 = 9.04 +/- 1.07 nM; EC50 = 17.1 +/-
      3.5 nM). A chimera which included part of TM-3 (CH-4) demonstrated binding and
      signalling (IC50 = 8.33 +/- 0.14 nM; EC50 = 467.5 +/- 173.6 pM) similar to the
      wild type receptor (IC50 = 1.33 +/- 0.19 nM; EC50 = 497.9 +/- 211.7 pM).
      Surprisingly constructs CH-2 and CH-3, while devoid of detectable 125I-GLP-1
      binding, were capable of eliciting GLP-1-specific cAMP production (EC50s CH-2 =
      81.4 +/- 19.6 nM; CH-3 = 5.99 +/- 0.68 nM) suggesting that receptor activation is
      not completely dependent on high affinity receptor binding. These data clearly
      demonstrate that the NT domain of the GIP receptor acts as the ligand-specific
      binding domain and that the first transmembrane domain is important for receptor
      activation.

PMID- 9165062
TI  - The proteasome: a macromolecular assembly designed to confine proteolysis to a
      nanocompartment.
AB  - Significant progress has been made over the past few years in elucidating the
      structural principles and the enzymatic mechanism of the 20S proteasome. As a
      result, the proteasome has become the prototype of a new family of enzymes, the
      Ntn hydrolases, as well as a paradigm for macromolecular assemblies that confine
      their proteolytic activity to an inner nanocompartment. Since access to this
      nanocompartment is restricted to unfolded substrate polypeptides, the 20S
      proteasome must be functionally linked to a substrate recognition and unfolding
      machinery. In eukaryotes this is provided by the 19S 'cap' complex, which
      associates with the 20S core to form the 26S proteasome, a protease capable of
      degrading ubiquitinated proteins in an ATP-dependent manner.

PMID- 9165063
TI  - New insights into the mechanisms and importance of the proteasome in
      intracellular protein degradation.
AB  - Recent studies of the 20S proteasome from Thermoplasma acidophilum have uncovered
      some fundamental new properties of its catalytic mechanism. Unlike conventional
      proteases, 20S and 26S proteasomes degrade protein substrates in a highly
      processive fashion. They cleave a protein substrate to small peptides before
      attacking another substrate molecule. This processive behavior is an inherent
      feature of the 20S particle not requiring cofactors or ATP hydrolysis. Recently,
      we have described a proteasome-like particle, HslVU, in Escherichia coli. HslVU
      is a two-component ATP-dependent protease composed of the proteasome-related
      peptidase HslV (beta-subunit) and the ATPase HslU. In active HslVU complex,
      cleavage of small peptides and proteins requires the presence of ATP. EM analysis
      revealed that HslV and HslU are both ring-shaped particles and that the active
      HslVU complex is a cylindrical four-ring structure, composed of HslV, a two-ring
      dodecamer, sandwiched between HslU rings. Elucidation of its mode of action may
      help us understand the role of ATP in function of the 26S proteasome. Several
      proteasome-specific inhibitors have been recently identified which block the
      function of proteasome in vivo. These agents have proven very useful to clarify
      the intracellular function of the proteasome. In mammalian cells, both the rapid
      degradation of short-lived regulatory proteins and of abnormal polypeptides and
      the slower degradation of long-lived proteins are blocked by these agents. Thus,
      in mammalian cells, the proteasome is the site for the degradation of most cell
      proteins. In contrast, in budding yeast, proteasome inhibitors block the
      degradation of short-lived proteins but not the breakdown of long-lived proteins,
      which can be blocked by inhibitors of vacuolar proteases. The inhibition of
      proteasome function in yeast and mammalian cells, presumably by causing an
      accumulation of unfolded proteins, triggers the expression of heat shock proteins
      and concomitantly increases cell resistance to high temperature and various toxic
      insults.

PMID- 9165064
TI  - Structural and functional aspects of papain-like cysteine proteinases and their
      protein inhibitors.
AB  - Cysteine proteinases are widely distributed among living organisms. According to
      the most recent classifications (Rawlings and Barrett, 1993, 1994), they can be
      subdivided on the basis of sequence homology into 14 or even 20 different
      families, the most important being the papain and the calpain families. The
      papain-like cysteine proteinases are the most abundant among the cysteine
      proteinases. The family consists of papain and related plant proteinases such as
      chymopapain, caricain, bromelain, actinidin, ficin, and aleurain, and the
      lysosomal cathepsins B, H, L, S, C and K. Most of these enzymes are relatively
      small proteins with Mr values in the range 20000-35000 (reviewed in Brocklehurst
      et al., 1987; Polgar, 1989; Rawlings and Barrett, 1994; Berti and Storer, 1995),
      with the exception of cathepsin C, which is an oligomeric enzyme with Mr
      approximately 200000 (Metrione et al., 1970; Dolenc et al., 1995). A number of
      cysteine proteinases are located within lysosomes. Four of them, cathepsins B, C,
      H and L, are ubiquitous in lysosomes of animals, whereas cathepsin S has a more
      restricted localisation (Barrett and Kirschke, 1981; Kirschke and Wiederanders,
      1994). The enzymes, except cathepsin C, are endopeptidases (reviewed in Kirschke
      et al., 1995), although cathepsin B was found also to be a dipeptidyl
      carboxypeptidase (Aronson and Barrett, 1978) and cathepsin H also an
      aminopeptidase (Koga et al., 1992). Cathepsin C is a dipeptidyl aminopeptidase,
      but at higher pH it exhibits also dipeptidyl transferase activity (reviewed in
      Kirschke et al., 1995). Among the lysosomal cysteine proteinases, cathepsin L was
      found to be the most active in degradation of protein substrates, such as
      collagen, elastin and azocasein (Barrett and Kirschke, 1981; Maciewicz et al.,
      1987; Mason et al., 1989), arid cathepsin B the most abundant (Kirschke and
      Barrett, 1981). All the enzymes are optimally active at slightly acidic pH,
      although their pH optima for degradation of synthetic substrates vary from 5.5
      for cathepsin L to 6.8 for cathepsin H (reviewed in Kirschke et al., 1995).
      Several other lysosomal cysteine proteinases, such as cathepsins N, T and K, are
      known, although their properties are less well characterised (reviewed in
      Kirschke et al., 1995). In particular cathepsin K has attracted recent interest
      (Bromme et al., 1996; Shi et al., 1995; Bossard et al., 1996; Drake et al., 1996)
      and was found to be expressed specifically in osteoclasts (Drake et al., 1996)
      with properties similar to cathepsin L (Bossard et al., 1996).

PMID- 9165066
TI  - Pancreatic procarboxypeptidases: oligomeric structures and activation processes
      revisited.
AB  - The activation peptides of procarboxypeptidases of the A1 type act in a post
      activation mechanism of control, limiting the expression of activity immediately
      after the limited proteolysis has occurred. This effect is due to structural
      complementarity between the enzymatic moiety and the released fragments, and is
      further enhanced by the occurrence of procarboxypeptidase A1 in oligomeric
      complexes of different type depending on the species studied. In those complexes,
      the activation segment has an important role in the stabilisation of the
      quaternary structure. The relationship between oligomeric structure and
      activation is reviewed here for two of the most extensively studied systems.

PMID- 9165065
TI  - Activation mechanisms of matrix metalloproteinases.
AB  - Matrix metalloproteinases (MMPs), also called matrixins, function in the turnover
      of extracellular matrix components. These enzymes are considered to play
      important roles in embryo development, morphogenesis and tissue remodeling, and
      in diseases such as arthritis, periodontitis, glomerulonephritis,
      atherosclerosis, tissue ulceration, and in cancer cell invasion and metastasis.
      All MMPs are synthesized as preproenzymes and most of them are secreted from the
      cells as proenzymes. Thus, the activation of these proenzymes is one of the
      critical steps that leads to extracellular matrix breakdown. This review
      describes recent progress made to elucidate the activation mechanisms of pro
      matrixins which include extracellular stepwise activation common to most proMMPs,
      cell surface activation of progelatinase A and procollagenase 3, and
      intracellular activation of prostromelysin 3 and pro-membrane-type-1 MMP.

PMID- 9165067
TI  - One century of protein crystallography: the phycobiliproteins.
AB  - The physical principles that underlay the rapid and efficient energy transfer
      from the light absorbing phycobilisomes to the reaction centre are conceivable
      from the knowledge of the exact three-dimensional structure of the
      phycobiliproteins and chromophores that are involved. The structure of the
      components and their assembly in the phycobilisomes could be determined by the
      structure analysis of X-ray data derived from phycobiliprotein crystals. Reports
      about these very aesthetic and brilliantly colored crystals have been published
      for more than a hundred years but it was only in the last decade that the
      structures of the different members of the phycobiliprotein family were solved
      for the first time at atomic resolution--all of them in Martinsried at the Max
      Planck-Institut fur Biochemie. Despite the appearance of common structural
      principles the most important finding was that very subtle modifications in the
      structure and environment of the chromophores are sufficient to establish a
      highly specific light harvesting system in which the phycobiliproteins function
      with great cooperativity and efficiency.

PMID- 9165068
TI  - Annexins: from structure to function.
AB  - Annexins are a family of calcium-dependent phospholipid-binding proteins. They
      are abundant in the eukaryotic kingdom. Though structurally well investigated in
      the last twenty years the in vivo function of the annexins is still unclear. The
      determination of the crystal structure of human annexin V was the first milestone
      in the structural investigation of this protein family. Succeedingly, a variety
      of three-dimensional structures of annexin crystals as well as of membrane bound
      annexins were solved. They should provide tools to understand the in vivo
      function of the annexin family. Based on the structural knowledge mutagenesis
      studies and biophysical investigations were started to elucidate possible
      functions of annexins like membrane binding and ion channel activity.

PMID- 9165069
TI  - The pathway from GTP to tetrahydrobiopterin: three-dimensional structures of GTP
      cyclohydrolase I and 6-pyruvoyl tetrahydropterin synthase.
AB  - The complex organic chemistry involved in the transformation of GTP to
      tetrahydrobiopterin is catalysed by only three enzymes: GTP cyclohydrolase I, 6
      pyruvoyltetrahydropterin synthase and sepiapterin reductase. The committing
      reaction step from GTP to dihydroneopterin triphosphate is catalysed by GTP
      cyclohydrolase I and requires no cofactor. 6-Pyruvoyl tetrahydropterin synthase,
      a Zn-dependent metalloprotein, transforms dihydroneopterin triphosphate into 6
      pyruvoyltetrahydropterin in the presence of Mg(II). Sepiapterin reductase is a
      NADPH-dependent short-chain dehydrogenase which reduces 6
      pyruvoyltetrahydropterin to BH4. Here we review the structural and mechanistic
      information on the biosynthetic pathway from GTP to BH4 on the basis of the
      recently determined crystal structures of CYH and PTPS.

PMID- 9165070
TI  - Structure and reaction mechanism of L-arginine:glycine amidinotransferase.
AB  - L-Arginine:glycine amidinotransferase (AT) catalyzes the committed step in
      creatine biosynthesis by formation of guanidinoacetic acid, the direct precursor
      of creatine. The X-ray structure of the human enzyme shows a novel fold with
      fivefold pseudosymmetry of beta beta alphabeta-modules. These modules enclose the
      active site compartment of the basket-like structure. The active site of AT lies
      at the bottom of a very narrow channel and contains a catalytic triad with the
      residues Cys-His-Asp. The transamidination reaction follows a ping-pong mechanism
      and is accompanied by large conformational changes. During catalysis the amidino
      group is covalently attached to the active site cysteine to give an amidino
      cysteine intermediate.

PMID- 9165071
TI  - Plant glutathione S-transferases and herbicide detoxification.
AB  - Glutathione S-transferases (GSTs) are a family of multifunctional enzymes
      involved in the metabolism of xenobiotics and reactive endogenous compounds. The
      interest in plant GSTs may be attributed to their agronomic value, since it has
      been demonstrated that glutathione conjugation for a variety of herbicides is the
      major resistance and selectivity factor in plants. The structure of the
      Arabidopsis thaliana isoenzyme, the first plant GST whose structure has been
      solved, may serve as a model system for the understanding of herbicide
      selectivity in crops.

PMID- 9165072
TI  - Feedback inhibition of dihydrodipicolinate synthase enzymes by L-lysine.
AB  - Dihydrodipicolinate synthase (DHDPS) is the first enzyme unique to the lysine
      biosynthetic pathway and is feedback regulated by L-lysine in plants and some
      bacteria. The allosteric binding site has been localized by X-ray crystallography
      and is in agreement with reported mutations of plant DHDPS enzymes, which confer
      insensitivity to feedback inhibition. Three possible elements of the mechanism of
      lysine inhibition are discussed.

PMID- 9165073
TI  - Chalcogen-analogs of amino acids. Their use in X-ray crystallographic and folding
      studies of peptides and proteins.
AB  - Using methionine-auxotrophic Escherichia coli strains quantitative biosynthetic
      replacement of the methionine residues by seleno- and telluromethionine but not
      by methoxinine was achieved in various model proteins, clearly indicating a
      limited tolerance in the editing range of methionyl-tRNA synthetase. For
      expression of the protein variants the acetyl derivatives of the chalcogen
      analogs of methionine, obtained by a new and highly efficient synthetic
      procedure, proved to be the ideal source in the growth media as they were found
      to be significantly more stable than the underivatized methionine analogs. The
      conformational properties in solution, the folding and unfolding parameters as
      well as X-ray crystallographic data confirmed the highly isomorphous character of
      the atomic mutants and thus the usefulness of this concept in X-ray analysis of
      proteins. Quantitative replacement of cysteine residues by selenocysteine has
      recently been achieved using cysteine-auxotrophic E. coli strains, but a
      selective replacement of cysteine residues by employing the natural translational
      machinery of selenocysteine is also conceivable. We have therefore performed a
      detailed study on synthetic selenocysteine-peptides in order to determine the
      redox potential of this cysteine analog, and thus the ability of related peptide
      and protein analogs to undergo the correct oxidative folding. Since the redox
      potential of selenocysteine was found to be significantly more reducing than that
      of the parent amino acid, selective formation of a diselenide bridge in presence
      of additional cysteine residues is highly favored as well documented in the case
      of the synthetic bis-selenocysteine-endothelin I analog. These results confirm
      that even cysteine residues may represent an interesting target for the design
      and expression of isomorphous heteroatomic analogs of proteins.

PMID- 9165074
TI  - The suitability of Ta6Br12(2+) for phasing in protein crystallography.
AB  - The title compound Ta6Br12(2+) is of interest for the analysis of biological
      structures as a heavy metal derivative with great potential for the structure
      determination of large protein systems. In macromolecular crystallography the
      phases of the measured structure factor amplitudes have to be determined by
      compounds that produce measurable changes of the diffraction intensities.
      Ta6Br12(2+) uniquely meets the demands of a heavy metal derivative and is an
      important tool for phase determination, especially considering the structure
      determination of large protein systems.

PMID- 9165075
TI  - Titration and mapping of the active site of cysteine proteinases from
      Porphyromonas gingivalis (gingipains) using peptidyl chloromethanes.
AB  - Porphyromonas gingivalis is one of the major pathogens associated with
      periodontal disease and releases powerful cysteine proteinases known as the
      gingipains, which are key virulence factors for this organism. The three forms of
      gingipains, gingipain R1, gingipain R2 (gingipain Rs) and gingipain K, which
      cleave specifically after arginine (R) or lysine (K) residues, were characterized
      in terms of the kinetics of their interaction with a wide range of synthetic
      peptidyl chloromethane inhibitors and a peptidyl (acyloxy)methane. Chloromethane
      inhibitors were found to inhibit all the enzymes to varying degree dependent on
      the peptidyl components of the inhibitor. Thus, inhibitors containing a basic
      residue at P1 rapidly inactivated the gingipains and some specificity could be
      seen at the P2 site. The (acyloxy)methane inhibitor, Cbz-Phe-Lys-CH2OCO-2,4,6-Me3
      Ph, was very specific in its rapid inhibition of gingipain K over the gingipains
      R. This inhibitor, together with the peptidyl chloromethanes, D-Phe-Pro-Arg-CH2Cl
      and D-Phe-Phe-Arg-CH2Cl, which reacted most rapidly with the Arg-specific
      proteinases, could be used to active site titrate purified forms of the enzymes
      and enzymes found in crude fractions such as intact P. gingivalis cells, vesicles
      or membrane fractions. From these titrations it was evident that gingipains R
      were always in an excess of about 3-fold over gingipain K and that the gingipains
      as a whole made up 85% of the proteolytic activity associated with the bacterium.
      The elucidation of the kinetics of inhibition by the range of compounds and the
      development of the titration method for gingipains will considerably aid in
      future studies on the proteases elaborated by P. gingivalis.

PMID- 9165076
TI  - Inhibition of the interaction of urokinase-type plasminogen activator (uPA) with
      its receptor (uPAR) by synthetic peptides.
AB  - Focusing of the serine protease urokinase-type plasminogen activator (uPA) to the
      cell surface via interaction with its specific receptor (uPAR, CD87) is an
      important step for tumor cell invasion and metastasis. The ability of a synthetic
      peptide derived from the uPAR-binding region of uPA (comprising amino acids 16-32
      of uPA; uPA(16-32)) to inhibit binding of fluorescently labeled uPA to uPAR on
      human promyeloid U937 cells was assessed by quantitative flow cytofluorometric
      analysis (FACS) and compared to the inhibitory capacities of other synthetic
      peptides known to interfere with uPA/uPAR-interaction. An about 3000-fold molar
      excess of uPA(16-32) resulted in 50% inhibition of pro-uPA binding to cell
      surface-associated uPAR. Using a solid-phase uPA-ligand binding assay employing
      recombinant soluble uPAR coated to microtiter plates, the minimal binding region
      of wild-type uPA was determined. The linear peptide uPA(19-31) and its more
      stable disulfide-bridged cyclic form (cyclo(19,31)uPA(19-31)) displayed uPAR
      binding activity whereas other peptides such as uPA(18-30), uPA(20-32) or uPA(20
      30) did not react with uPAR. Cyclic peptide derivatives of cyclo(19,31)uPA(19-31)
      in which certain amino acids were deleted and/or replaced by other amino acids as
      well as uPAR-derived wild-type peptides did also not inhibit uPA/uPAR
      interaction. Therefore, the present investigations identified cyclo(19,31)uPA(19
      31) as a potential lead structure for the development of uPA-peptide analogues to
      block uPA/uPAR-interaction.

PMID- 9165077
TI  - Structural investigation of proteasome inhibition.
AB  - The novel proteolytic mechanism of the 20S proteasome from T. acidophilum has
      been investigated by X-ray crystallography using small-molecule inhibitors and
      substrate analogues. The 20S proteasome degrades unfolded substrates into small
      peptides of a defined length. Calpain inhibitor II, chymostatin and lactacystin
      all bind in the previously identified active site pocket near Thr1 of all
      fourteen beta-subunits. The chromogenic substrate analogue Suc-LLVY-AMC binds in
      the same pocket of the proteolytically inactive T1A mutant of the beta-subunit,
      but with a significantly altered geometry. The heavy-atom cluster Ta6Br12(2+)
      used in X-ray structure determination occupies seven sites in the inner
      compartment of the proteasome and exhibits inhibition of the chymotrypsin-like
      activity. Other effectors of proteasome activity showed no significant difference
      in electron density.

PMID- 9165078
TI  - Screening for molecules interacting with proteasomes in Thermoplasma acidophilum.
AB  - Thermoplasma acidophilum cell extracts were fractionated by gel filtration.
      Proteasomes were eluted as two major peaks. The first one (molecular mass(r)
      about 2 MDa) contained proteasomes associated with DNA/protein complexes.
      Proteasomes eluted in the other peak were partially resolved into three subpeaks
      and based on their preferential hydrolysis of casein, Z-GGL-MCA, and suc-LLVY
      MCA, were designated C, L and Y, respectively. Further purification of
      proteasomes from peak Y resulted in a homogenous enzyme preparation, whereas
      proteasomes purified from peak C contained a homomultimeric protein composed of
      20 kDa subunits. Thus, association of proteasomes with this protein seems to be
      responsible for the observed increase in molecular mass and for inhibition of
      caseinolytic activity by Ca2+-ions.

PMID- 9165079
TI  - Molecular basis of proteolytic activation of Sendai virus infection and the
      defensive compounds for infection.
AB  - It has been proposed that the pathogenicity of Sendai virus is primarily
      determined by a host cellular protease(s) that activates viral infectivity by
      proteolytic cleavage of envelope fusion glycoproteins. We isolated a trypsin-like
      serine protease, tryptase Clara, localized in and secreted from Clara cells of
      the bronchial epithelium of rats. The enzyme specifically cleaved the precursor
      of fusion glycoprotein F0 of Sendai virus at residue Arg116 in the consensus
      cleavage motif, Gln(Glu)-X-Arg, resulting in the presentation of the membrane
      fusion domain in the amino-terminus of the F1 subunit. Administration of an
      antibody against tryptase Clara in the airway significantly inhibited the
      activation of progeny virus and multiple cycles of viral replication, thus
      reducing the mortality rate. These findings indicate that tryptase Clara in the
      airway is a primary determinant of Sendai virus infection and that proteolytic
      activation occurs extracellularly. We identified two cellular inhibitory
      compounds against tryptase Clara in bronchial lavage. One was a mucus protease
      inhibitor, a major serine protease inhibitor of granulocyte elastase in the
      lining fluids of the human respiratory tract, and the other was a pulmonary
      surfactant which may adsorb the enzyme, resulting in its inactivation. These
      compounds inhibited virus activation by tryptase Clara in vitro and in vivo, but
      did not themselves affect the hemagglutination and the infectivity of the virus.
      The functional domain of the mucus protease inhibitor against the enzyme, which
      is organized in two homologous N- and C-terminal domains, is located in the C
      terminal. Administration of these compounds in the airway may be useful for
      preventing infection with Sendai virus.

PMID- 9165080
TI  - Binding of 92 kDa and 72 kDa progelatinases to insoluble elastin modulates their
      proteolytic activation.
AB  - 92 kDa and 72 kDa gelatinases, two neutral proteinases exhibiting elastinolytic
      activity and secreted as zymogens by aortic smooth muscle cells, were shown to
      bind to insoluble elastin. The active form of each enzyme interacted with
      substrate more avidly than latent form. Once bound to insoluble elastin, 92 kDa
      progelatinase was totally unaffected by any potential activators tested (tissue
      kallikrein, neutrophil elastase, plasmin, and stromelysin-1), except
      aminophenylmercuric acetate (APMA). Binding of 72 kDa progelatinase to insoluble
      elastin induced a fast autoactivation of the proenzyme followed by its
      inactivation. This process can be partly inhibited by tissue inhibitor of matrix
      metalloproteinases-2 (TIMP-2), EDTA and a synthetic inhibitor of matrix
      metalloproteinases (BB-94). Such an autoactivation process was also partially
      observed following adsorption of 72 kDa gelatinase to elastin-derived peptides
      but not to gelatin. Therefore, elastin can act as a template to direct its own
      proteolysis by 72 kDa gelatinase; such a mechanism could be relevant to the focal
      elastolysis in the arterial wall during arteriosclerosis.

PMID- 9165082
TI  - Horseshoe crab coagulogen is an invertebrate protein with a nerve growth factor
      like domain.
AB  - The rapid clotting of the horseshoe crab hemolymph is essential for both its host
      defense and hemostasis. It is mediated by the clotting cascade system which
      consists of four serine proteinase zymogens and the clottable protein coagulogen.
      Coagulogen, the target protein of the cascade, is converted to an insoluble gel
      upon activation of the cascade, giving rise to clot formation. Thus this cascade
      is reminiscent of the mammalian blood coagulation leading to fibrin clot. The
      structural analysis of coagulogen revealed a polypeptide fold and disulfide
      bridge pattern in the C-terminal half of the molecule very similar to nerve
      growth factor (NGF). This finding assigns coagulogen as the first structurally
      characterized invertebrate protein which belongs to the cystine knot superfamily.
      The putative structural similarity of coagulogen and the Drosophila morphogen
      Spaetzle as well as the homology of its processing proteinases suggests a common
      origin of the two functionally different cascades. This would exemplify a
      divergent evolution of two proteinase cascades having totally different functions
      from common ancestors in a long history of evolution.

PMID- 9165081
TI  - Purification and primary structure determination of a Bowman-Birk trypsin
      inhibitor from Torresea cearensis seeds.
AB  - A Bowman-Birk-type trypsin inhibitor (TcTI) was purified from seeds of Torresea
      cearensis, a Brazilian native tree of the Papilionoideae sub-family of
      Leguminosae. Three forms of the inhibitor were separated by anion exchange
      chromatography. The major form with 63 amino acids was entirely sequenced; it
      shows a high structural similarity to the Bowman-Birk inhibitors from other
      Leguminosae. The putative reactive sites of the inhibitor are a lysine residue at
      position 15 and a histidine at position 42 as identified by alignment to related
      inhibitors, direct chemical modification and specific enzymatic degradation.
      Immunoprecipitation with antibodies raised in rats is reduced significantly if
      TcTI is complexed with chymotrypsin and, to a lesser degree, if complexed with
      trypsin. TcTI forms a ternary complex with trypsin and chymotrypsin. The binary
      complexes with trypsin or chymotrypsin were isolated by gel filtration.
      Dissociation constants of the complexes with trypsin, plasmin, chymotrypsin, and
      factor XIIa are 1, 36, 50, 1450 nM, respectively; human plasma kallikrein, human
      factor Xa, porcine pancreatic kallikrein and bovine thrombin are not inhibited.
      TcTI prolongs blood clotting time of the contact phase activation pathway by
      inhibition of FXIIa.

PMID- 9165083
TI  - cDNA cloning, tissue distribution, and subcellular localization of horseshoe crab
      big defensin.
AB  - A full-length cDNA for horseshoe crab big defensin with a strong antimicrobial
      activity was obtained from a hemocyte cDNA library. The open reading frame of the
      cDNA coded for an NH2-terminal signal sequence followed by a propeptide and the
      mature big defensin. The propeptide is linked to the mature protein through an 
      Arg-X-Lys/Arg-Arg- motif, the processing site for Kex2-like proteases. Northern
      blot analysis revealed that big defensin is expressed in all the tissues tested,
      suggesting that big defensin plays an important role not only in hemocytes but
      also in other tissues for host defense. The subcellular localization, determined
      by immunocytochemistry at ultrastructural level, confirmed the previous findings
      obtained by biochemical analysis that big defensin locates in both small and
      large granules in hemocytes. Big defensin is the first example to demonstrate the
      existence of broad tissue distribution in horseshoe crab.

PMID- 9165084
TI  - Isolation, cloning, sequence analysis and X-ray structure of dimethyl
      sulfoxide/trimethylamine N-oxide reductase from Rhodobacter capsulatus.
AB  - The periplasmic enzyme dimethyl sulfoxide/trimethylamine N-oxide reductase
      (DMSOR/TMAOR) from the photosynthetic purple bacterium Rhodobacter capsulatus
      functions as the terminal electron acceptor in its respiratory chain. The enzyme
      catalyzes the reduction of highly oxidized substrates like dimethyl sulfoxide
      (DMSO) or trimethylamine N-oxide (TMAO). At a molybdenum redox centre, two single
      electrons are transferred from cytochrome c556 to the substrate, e.g. DMSO,
      generating dimethyl sulfide (DMS) and water. The operon encoding this enzyme was
      isolated, cloned and sequenced, and its chromosomal location determined. It was
      shown by analytical and crystallographic data that DMSOR and TMAOR are identical
      enzymes. Degenerate primers were derived from short peptide sequences and a 700
      bp fragment was amplified by nested PCR, subsequently cloned and radioactively
      labeled to screen a prepared lambda DASH library. Positive lambda clones were
      subcloned into pBluescript and subsequently transformed into Escherichia coli to
      sequence the DMSOR/TMAOR operon. By an optimized protein purification high yields
      (5 mg protein/l culture) with a specific activity of 30 U/mg were obtained. The
      molecular mass was experimentally determined by electrospray mass spectroscopy
      (MS) to be 85034 Da and from the deduced amino acid sequence of the apoenzyme to
      be 85033 Da. The enzyme was crystallized in space group P4(1)2(1)2 with unit cell
      dimensions of a = b = 80.7 A and c = 229.2 A diffracting beyond 1.8 A. The three
      dimensional structure was solved by a combination of multiple isomorphous
      replacement (MIR) and molecular replacement techniques. The atomic model was
      refined to an R-factor of 0.169 for 57394 independent reflections. The spherical
      protein consists of four domains with a funnel-like cavity that leads to the
      freely accessible metal-ion redox center. The sole bis(molybdopterin guanine
      dinucleotide)molybdenum cofactor (1541 Da) of the single chain protein has the
      molybdenum ion bound to the cis-dithiolene group of only one molybdopterin
      guanine dinucleotide (MGD) molecule. In addition, two oxo ligands and the oxygen
      of a serine side chain are bound to the molybdenum ion.

PMID- 9165085
TI  - Organization of the DMSO respiratory operon of Rhodobacter capsulatus and its
      consequences for homologous expression of DMSOR/TMAOR.
AB  - In this report we describe the organization of the respiratory operon from the
      non-sulfur photosynthetic bacterium Rhodobacter capsulatus and its consequences
      for homologous expression of recombinant dimethylsulfoxide/trimethylamine N-oxide
      reductase (DMSOR/TMAOR). This enzyme is of special interest since molybdopterin
      dinucleotide is its only cofactor. Overexpression of the dmsA gene and production
      of active enzyme is not possible in E. coli because this bacterium is unable to
      supply the required complex molybdopterin cofactor. To investigate the catalytic
      mechanism and binding of the cofactor by structure-based site-directed
      mutagenesis, and to ensure sufficient production and incorporation of the complex
      cofactor, we designed a system for homologous expression in R. capsulatus.

PMID- 9165086
TI  - Implications for the catalytic mechanism of the vanadium-containing enzyme
      chloroperoxidase from the fungus Curvularia inaequalis by X-ray structures of the
      native and peroxide form.
AB  - Implications for the catalytic mechanism of the vanadium-containing
      chloroperoxidase from the fungus Curvularia inaequalis have been obtained from
      the crystal structures of the native and peroxide forms of the enzyme. The X-ray
      structures have been solved by difference Fourier techniques using the atomic
      model of the azide chloroperoxidase complex. The 2.03 A crystal structure (R =
      19.7%) of the native enzyme reveals the geometry of the intact catalytic vanadium
      center. The vanadium is coordinated by four non-protein oxygen atoms and one
      nitrogen (NE2) atom from histidine 496 in a trigonal bipyramidal fashion. Three
      oxygens are in the equatorial plane and the fourth oxygen and the nitrogen are at
      the apexes of the bipyramid. In the 2.24 A crystal structure (R = 17.7%) of the
      peroxide derivate the peroxide is bound to the vanadium in an eta2-fashion after
      the release of the apical oxygen ligand. The vanadium is coordinated also by 4
      non-protein oxygen atoms and one nitrogen (NE2) from histidine 496. The
      coordination geometry around the vanadium is that of a distorted tetragonal
      pyramid with the two peroxide oxygens, one oxygen and the nitrogen in the basal
      plane and one oxygen in the apical position. A mechanism for the catalytic cycle
      has been proposed based on these X-ray structures and kinetic data.

PMID- 9165087
TI  - Dimer interface of glutathione S-transferase from Arabidopsis thaliana: influence
      of the G-site architecture on the dimer interface and implications for
      classification.
AB  - The three-dimensional structure of glutathione S-transferase from Arabidopsis
      thaliana has been solved at 2.2 A resolution (Reinemer et al., 1996). The enzyme
      forms a dimer of two identical subunits. The structure shows a new G-site
      architecture and a novel and unique dimer interface. Each monomer of the protein
      forms a separate G-site. Therefore, the requirements on the dimer interface are
      reduced. As a consequence, the interactions between the monomers are weaker and
      residues at the dimer interface are more variable. Thus, the dimer interface
      looses its relevance for a classification of plant glutathione S-transferases and
      the formation of heterodimers becomes even more difficult to predict.

PMID- 9165088
TI  - Mode of action of cystathionine beta-lyase.
AB  - Cystathionine beta-lyase (CBL) is a member of the gamma-family of pyridoxal-5'
      phosphate (PLP)-dependent enzymes (Alexander et al., 1994) that cleave
      C(beta,gamma)-S bonds of a broad variety of substrates. Recently, we reported the
      X-ray crystal structures of CBL and the CBL-trifluoroalanine inactivation complex
      at 1.83 A and 2.3 A resolution, respectively. The structures explicitly reveal
      the cofactor and substrate binding pockets. Spectral analysis of substrate
      turnover indicates a change of hydrophobicity in the microenvironment of the
      aldimine bond. In combination with further spectroscopic data, crystallographic
      evidence permits the formulation of a likely reaction mechanism.

PMID- 9165089
TI  - Crystallographic analysis of phosphoglycerate kinase from the hyperthermophilic
      bacterium Thermotoga maritima.
AB  - Phosphoglycerate kinase from the hyperthermophilic bacterium Thermotoga maritima
      has been co-crystallized with its substrate 3-phosphoglycerate and the ATP
      analogue AMP-PNP using the vapour diffusion method. Crystals were obtained from a
      solution containing polyethylene glycol (MW 3000/8000) as precipitating agent. A
      complete diffraction data set from orthorhombic crystals was collected up to 2.0
      A resolution. The TmPGK crystallizes in the space group P2(1)2(1)2 (cell
      dimensions: a = 62.0 A, b = 76.9 A, c = 87.5 A) with one molecule in the
      asymmetric unit. The structure was solved by Patterson search methods using
      Bacillus stearothermophilus PGK as a search model and was refined to a
      crystallographic R factor of 22.0%. Compared to the enzyme from B.
      stearothermophilus, horse, pig and yeast, the Thermotoga enzyme exhibits a
      drastically reduced interdomain angle, similar to the one reported for PGK from
      Trypanosoma brucei. Here we present crystallographic data of the first high
      resolution structure of a PGK in largely closed conformation, complexed with the
      two products of the catalyzed reaction, and, at the same time, the first PGK
      structure from a hyperthermophilic organism.

PMID- 9165090
TI  - Structural features correlated with the extreme thermostability of 1[4Fe-4S]
      ferredoxin from the hyperthermophilic bacterium Thermotoga maritima.
AB  - Understanding the molecular mechanisms behind extreme temperature stability is of
      relevance for the protein folding problem and for designing proteins for
      industrial and medical applications. A powerful approach for understanding the
      structural basis of thermostability is the comparison of high resolution
      structures of homologous proteins from mesophiles and thermophiles. The 1.75 A
      crystal structure of Thermotoga maritima 1[4Fe-4S] ferredoxin was compared with
      those of mesophilic ferredoxins. Detailed analysis of structural differences
      reveals that thermostability is achieved without large changes of the overall
      polypeptide chain folding. The most striking differences include the formation of
      additional hydrogen bonding networks involving both side-chain and main-chain
      atoms. These networks are mainly connecting turns and strongly fix the N-terminus
      to the central core of the protein, increasing the overall rigidity of Thermotoga
      maritima ferredoxin. Other possibly stabilizing factors are the shortening of a
      solvent exposed surface loop, the increased content of alanines in the second
      alpha-helix, and the replacement of three residues close to the iron-sulfur
      cluster, which are in energetically unfavourable conformations in other
      ferredoxins, by glycines.

PMID- 9165091
TI  - Interaction of Salmonella phage P22 with its O-antigen receptor studied by X-ray
      crystallography.
AB  - The O-antigenic repeating units of the Salmonella cell surface
      lipopolysaccharides (serotypes A, B and D1) serve as receptors for phage P22.
      This initial binding step is mediated by the tailspike protein (TSP), which is
      present in six copies on the base plate of the phage. In addition to the binding
      activity, TSP also displays a low endoglycolytic activity, cleaving the
      alpha(1,3)-O-glycosidic bond between rhamnose and galactose of the O-antigenic
      repeats. The crystal structure of TSP in complex with receptor fragments allowed
      to identify the receptor binding site for the octasaccharide product of the
      enzymatic action of TSP on delipidated LPS and the active site consisting of
      Asp392, Asp395 and Glu359. The structure comprises a large right-handed parallel
      beta-helix of 13 turns. These fold independently in the trimer, whereas the N
      terminus forms a cap-like structure and the C-terminal parts of the three
      polypeptide strands merge to a single common domain. In addition, TSP has served
      as model system for the folding of large, multisubunit proteins. Its folding
      pathway is influenced by a large number of point mutations, classified as lethal,
      temperature sensitive or general suppressor mutations, which influence the
      partitioning between aggregation and the productive folding pathway.

PMID- 9165092
TI  - Substitution of lysine for arginine at position 199 of a hypoxanthine
      phosphoribosyltransferase interferes with binding of the primary substrate to the
      active site.
AB  - Lysine was substituted for a conserved arginine at position 199 of the
      schistosomal hypoxanthine phosphoribosyltransferase (HPRT). This resulted in a >
      or = 35-fold increase in the K(M) for binding phosphoribosyl-pyrophosphate
      (PRPP). The possible functional role of R199 in tertiary structure, as well as in
      the binding of PRPP, is interpreted in the context of the reported three
      dimensional structure for the human HPRT.

PMID- 9165093
TI  - Primary structure of the propeptide and factor VIII-binding domain of bovine von
      Willebrand factor.
AB  - A 2811 base-pair cDNA, encoding the amino-terminal part of the bovine pre-pro-von
      Willebrand factor, was characterized and sequenced. The deduced amino acid
      sequence shares significant homology with the human von Willebrand antigen II and
      the amino-terminal part of the factor VIII-binding domain of von Willebrand
      factor. In contrast to human, there is no RGD motif in the bovine von Willebrand
      antigen II. High levels of Cys, characteristic of D domains, are also found in
      bovine and the Cys position is markedly conserved between the two species.

PMID- 9165095
TI  - Three-dimensional structure of maize alpha-zein proteins studied by small-angle X
      ray scattering.
AB  - alpha-zeins of maize (Zea mays) that are storage proteins contain nine or ten
      tandem repeats comprising of about 20 amino acids. Small-angle X-ray scattering
      (SAXS) of alpha-zeins was measured in 70% (v/v) aqueous ethanol containing beta
      mercaptoethanol or without reagent in a protein concentration range of 2.0 to
      40.0 mg/ml. The overall radius of gyration of whole particles, Rg, and the
      corresponding radius of gyration of the cross-section, Rc, of reduced alpha-zeins
      are 4.00 +/- 0.03 nm and 1.39 +/- 0.05 nm, respectively, in the 70% (v/v) aqueous
      ethanol containing 2% (v/v) beta-mercaptoethanol. Analyses using the Rg and Rc
      values indicate that reduced alpha-zeins exist as asymmetric particles with the
      length of about 13 nm in the solution. A structural model is developed under
      assumption that each of tandem repeats units forms single alpha-helix and they
      are joined by glutamine-rich 'turns' or loops, as employed by Argos et al.,
      [Argos, O., Pedersen, K., Marks, M.D. and Larkins, B.A. (1982) J. Biol. Chem.
      257, 9984-9990] and Garratt et al. [Garratt, R., Oliva, G., Caracelli, I., Leite,
      A. and Arruda, P. (1993) Proteins Struc. Func. Genet. 15, 88-99], and that the
      longest dimension of 13 nm comes from linear stacking of the anti-parallel
      helices of tandem repeat in the direction perpendicular to the helical axis. The
      resultant model is presented by an elongated prism-like shape with an approximate
      axial ratio of 6:1.

PMID- 9165094
TI  - Cloning of the rat and human mitochondrial branched chain aminotransferases
      (BCATm).
AB  - The rat and human mitochondrial branched chain aminotransferase (BCAT(m)) cDNAs
      have been isolated and shown to encode mature proteins of 41.2 and 41.3 kDa with
      presequences of 27 amino acids. When rat BCAT(m) is overexpressed in COS-1 cells,
      the protein exhibits BCAT activity and correct processing of the mitochondrial
      targeting sequence. Southern blot analysis of genomic DNA from a panel of rodent
      human somatic cell hybrids revealed that the human BCAT(m) gene resides on
      chromosome 19 and the human cytosolic enzyme (BCAT(c)) gene on chromosome 12.
      Finally, the nomenclature BCAT1 for the cytosolic gene and BCAT2 for the
      mitochondrial BCAT gene is proposed.

PMID- 9165096
TI  - Biochemical and molecular characterization of a manganese peroxidase isoenzyme
      from Pleurotus ostreatus.
AB  - In this study we purified and investigated the catalytic properties of a
      manganese peroxidase isoenzyme produced by the fungus Pleurotus ostreatus in
      liquid medium with peptone as nitrogen source. The isoenzyme was purified to
      homogeneity by chromatography on Bio-Rad Q-cartridge, Sephacryl S-200 and Mono-Q
      with activity yield of 59% and a purification factor of 36. The P. ostreatus MnP
      obtained had the same pI (3.75) and N-terminal sequence as MnP-1 of Pleurotus
      eryngii produced in the same medium (both exhibiting Mn-independent activities on
      phenolic and non-phenolic substrates). However, the N-terminal sequence of this
      P. ostreatus isoenzyme differed from a previous published sequence of MnP from
      this fungus. The results obtained show the importance of media composition in the
      production of different isoenzymes within the same fungal species. We have also
      demonstrated by Southern blots that the different isoenzymes are probably encoded
      by different genes, and that the MnP genes in both Pleurotus species are similar
      but different to those of Phanerochaete chrysosporium.

PMID- 9165097
TI  - Kinetic evaluation of beta-neoendorphin hydrolysis by the somatic and testicular
      isozymes of human angiotensin-converting enzyme.
AB  - Angiotensin-converting enzyme (ACE) has both somatic and testicular isozymes, the
      former possessing two catalytically active domains, amino-terminal and carboxyl
      terminal, while the latter has only the carboxyl-terminal one. We compared
      hydrolysis processes of the nonapeptide beta-neoendorphin by the two isozymes of
      human ACE. Both isozymes hydrolyzed the peptide to Tyr1-Gly2-Gly3 by the
      sequential removal of carboxyl-terminal dipeptides in three consecutive steps.
      The rate constant values for the second step, conversion of beta-neoendorphin1-7
      to Leu-enkephalin, by the somatic isozyme in the presence of 10 or 200 mM NaCl
      were 4-fold higher than those for the first step, conversion of beta
      neoendorphin1-9 to beta-neoendorphin1-7. The k(cat) values of the somatic isozyme
      for beta-neoendorphin1-7 were 2-fold higher than those for beta-neoendorphin1-9,
      indicating that beta-neoendorphin1-7 is more rapidly hydrolyzed than beta
      neoendorphin1-9. The rate constant value for the second step at 10 mM NaCl was 5
      fold higher than that for the testicular isozyme. Similar extent of difference
      was also observed in k(cat) values for beta-neoendorphin1-7 between the two
      isozymes. These results suggest that the amino-terminal domain of the somatic
      isozyme mainly contributes to the conversion of beta-neoendorphin1-7 to Leu
      enkephalin at a low NaCl concentration. Optimal chloride concentrations for the
      individual steps of beta-neoendorphin1-9 hydrolysis differed between the two
      isozymes.

PMID- 9165098
TI  - Cloning and sequencing of a cDNA for firefly luciferase from Photuris
      pennsylvanica.
AB  - The first cDNA from the Photurinae subfamily of the Lampyridae encoding a firefly
      luciferase from lantern mRNA of Photuris pennsylvanica has been cloned,
      sequenced, the amino-acid sequence predicted and the sequence reported to
      GenBank. The cDNA was about 1.8 kb in length with the largest open reading frame
      coding for a 545-residue protein. The 5' noncoding region is 61 bp long and the
      3' noncoding region is 135 bp in length. There is a 24-nucleotide poly(A) tail.
      When the amino-acid residues are aligned, P. pennsylvanica contains 154 (about
      28% of the total residues) that are conserved in all 16 of the deduced luciferase
      sequences that are presently available. In this P. pennsylvanica luciferase, the
      amino acids at 276 of the positions are the same at corresponding positions of at
      least one of the other enzymes. There are two amino-acid differences between this
      luciferase and the unpublished sequence obtained by Dr. Keith Wood for a putative
      larval Photuris firefly luciferase cloned from a Maryland firefly. Signature
      amino-acid sequences and domains found in the deduced sequence are for adenylate
      kinase, the putative AMP-binding domain, luciferin 4-monooxygenase, 4-coumarate
      CoA ligase, long-chain fatty acid CoA ligase, 2-acylglycerophosphoethanolamine
      acyltransferase, the microbody-directing sequence, peptide-synthesizing
      complexes, and acyladenylate-synthesizing enzymes.

PMID- 9165099
TI  - Difference in interaction of fibronectin with type I collagen and type IV
      collagen.
AB  - In our studies on fibronectin, difference in binding to type I collagen and type
      IV collagen was observed and analysed. Four different fragments, which consist of
      I6-II1-II2-I7-I8-I9, I6-II1-II2-I7, I6-II1-II2, and I8-I9 within the collagen
      binding domain, have been isolated from proteolytic digests of fibronectin. The N
      terminal fragments of the collagen binding domain showed the binding affinity to
      both of type I and type IV collagens. On the other hand, the C-terminal portion
      of the domain, I8-I9, only bound to type I collagen. The newly developed
      monoclonal antibody FN 40, which recognizes type I9 homology repeat of the
      collagen binding domain, inhibited the binding of fibronectin to type I collagen
      in a dose-dependent manner. Three overlapping fragments, I6-II1-II2-I7, I6-II1
      II2-I7-I8, and I7-I8-I9, which have been expressed in Escherichia coli, showed
      the similar binding affinity to type IV collagen, whereas the fragment containing
      type I9 repeat (I7-I8-I9) showed the significantly stronger binding activity to
      type I collagen. In addition, the expressed fragment lacking I9 competitively
      inhibited the binding of fibronectin to type IV collagen. In contrast, the
      interference of this fragment to type I collagen binding activity of fibronectin
      was not significant. These data indicate that the collagen binding domain
      contains at least 2 sites for interaction with each type of collagen and that
      type I9 repeat is important for type I collagen binding, whereas I7 is for type
      IV collagen binding. Chemical modification studies revealed that the three
      dimensional structure of fibronectin is more important for type I collagen
      binding.

PMID- 9165100
TI  - Cloning, expression, purification, and characterization of the major core protein
      (p26) from equine infectious anemia virus.
AB  - The gene coding for the major core protein (p26) of the lentivirus equine
      infectious anemia virus (EIAV) was cloned from EIAV infected serum, expressed in
      E. coli, and the resultant protein purified to electrophoretic homogeneity. The
      protein was expressed in a soluble form and was purified by conventional protein
      separation methods. When analyzed by SDS-PAGE, under both reducing and non
      reducing conditions, the purified protein migrated as a 26 kDa monomer.
      Recombinant p26 (rp26), therefore, does not contain any intermolecular disulfide
      bond. Gel filtration chromatography also indicated that the protein occurs as a
      monomer in solution. Labeling of free sulphydryl groups with [1-14C]iodoacetamide
      suggests that none of the three cysteine residues of rp26 is involved in
      intramolecular disulfide bonds. The circular dichroism spectrum of rp26 was
      consistent with the following assignment of secondary structure elements: 51% a
      helix, 15% beta-turn, and 34% aperiodic. Fluorescencespectroscopy revealed that
      the three tryptophan residues in rp26 occupy two different environments. These
      data support the conclusion that the recombinant protein is folded into an
      ordered and probably native conformation. Immunoblotting and enzyme immunoassay
      with EIAV infected sera demonstrated that recombinant p26 protein may be useful
      for diagnostic purposes.

PMID- 9165101
TI  - Calcium-dependent and -independent binding of the pentraxin serum amyloid P
      component to glycosaminoglycans and amyloid proteins: enhanced binding at
      slightly acid pH.
AB  - Serum amyloid P component (SAP), a member of the pentraxin family of proteins,
      binds calcium-dependently to several ligands including glycosaminoglycans
      (GAG's). We have investigated the influence of pH on the Ca2(+)-dependent binding
      of SAP to solid phase GAG's and amyloid fibril proteins (AA and beta2M) by ELISA.
      An increase in the dose-dependent binding of SAP to heparan sulfate, AA-protein
      and beta2M was observed as the pH decreased from 8.0 to 5.0. Furthermore, a
      lower, but significant Ca2(+)-independent binding of SAP to heparan sulfate,
      dermatan sulfate, AA protein and the amyloid precursor protein beta2M was
      observed. This binding was also enhanced at slightly acid pH, most pronounced at
      pH 5.0. The results of this study indicate that SAP can exhibit both Ca2(+)
      dependent and -independent binding to ligands involved in amyloid fibril
      formation and that the binding is enhanced under conditions of slightly lowered
      pH.

PMID- 9165102
TI  - Kinetic studies on the oxidation of phenols by the horseradish peroxidase
      compound II.
AB  - Oxidation of substituted phenols by horseradish peroxidase compound II were
      studied using stopped-flow technique. Dissociation constants (K(D)) of HRP-II
      phenol complexes were deduced from the kinetic data. Magnitudes of K(D) fall in a
      relatively narrow range of 3-11 mM. These are comparable to 3-10 mM reported for
      the binding of substituted phenols to native HRP, suggesting that the mode of
      binding of phenols to native HRP and HRP compound II may be similar. pH
      dependence of the apparent second order rate constants (k(app)) of the reactions
      of all the phenols were determined. The k(app) values of reactions other than the
      reaction of tyrosine, were observed to increase in the acidic region but
      decreased in the alkaline region. The increase was attributed to the
      deprotonation of distal carboxylic acid residue on enzyme with pK(a) values of
      4.2-5.2. For tyrosine, however, the apparent second-order rate constant was
      observed to further increase non linearly on increasing the pH in the alkaline
      region. Results were interpreted quantitatively on the basis that protonated form
      of the enzyme reacted with the protonated form of the phenol with different
      individual rate constants.

PMID- 9165103
TI  - A nuclear paramagnetic relaxation study of the interaction of the
      cyclopentanedione substrate with chloroperoxidase.
AB  - Association of the physiological substrate cyclopentanedione (CPDO) with
      chloroperoxidase (CPO) was confirmed from both line-width and longitudinal
      relaxation time measurements of the proton NMR signals of CPDO. A dissociation
      constant of 33 mM for the enzyme-substrate complex was calculated from proton NMR
      relaxation experiments. Chloride ion does not affect the stability of the
      complex, but iodide ion greatly decreased the stability of the CPO-CPDO complex.
      Binding of cyanide ion to the heme iron center of CPO also decreased the
      stability of the CPO-CPDO complex. This result indicates the critical influence
      of perturbation in the heme active site on the affinity of CPO toward its
      substrate. Titration of CPO with CPDO revealed that CPDO does not bind directly
      to the heme iron of CPO. A distance of 7.1 A between the heme center of CPO and
      the protons of bound CPDO is deduced from the Solomon-Bloembergen relationship.
      This distance is 1 to 3 A shorter than those reported for the complexes formed
      between CPO and organic sulfide and unreactive phenol substrates, but the
      distance approximates that for reactive phenol substrates.

PMID- 9165104
TI  - One-electron photo-oxidation of reduced Desulfovibrio vulgaris flavodoxin on
      laser excitation at 355 nm.
AB  - Electron ejection from the reduced flavin in flavodoxin from Desulfovibrio
      vulgaris was obtained on exposure of the protein to the third harmonic radiation
      (354.7 nm) generated from a pulsed Nd/YAG laser. The results indicate that the
      reaction is due to stepwise two-photon excitation of the reduced flavin via the
      excited singlet state. The absorption spectrum of the neutral flavosemiquinone
      radical formed in this process was obtained. This spectrum remains stable over
      the time of study (0.2 ms) in the pH range studied, except for a slight evolution
      during the first microseconds, attributed to conformational readjustments of the
      active site. This two-photon excitation method provides a convenient means of
      generating the flavosemiquinone for ultrafast kinetic studies.

PMID- 9165105
TI  - Hatching enzyme from the sea-squirt Ciona intestinalis: purification and
      properties.
AB  - We have purified a 34 kDa hatching enzyme from the water in which the embryos of
      the sea-squirt Ciona intestinalis hatch. This enzyme was obtained in homogeneous
      form as judged from SDS-PAGE and HPLC gel filtration. The enzyme possesses
      proteolytic activity and is able to digest the chorion of the egg of C.
      intestinalis. It is a metalloproteinase and contains one atom of Zn per molecule.
      The optimum pH is 8.5. The enzyme shows hydrolytic activity towards the -CO-NH-
      bonds, which are hydrolyzed by the members of the serine proteinase family. It
      has a trypsin-like activity in that it cuts the bond of Arg and Lys at P1
      position of the scissile bond -P1-P1', but it differs from trypsin insofar as it
      hydrolyzes the peptide bond on either side of Arg and Lys. The purified enzyme is
      inhibited by the common metal-chelators and by the classical trypsin proteinase
      inhibitors. The apparent K(m) values at 37 degrees C and pH 8.5 toward tosyl-Gly
      Pro-Arg-NHNap, tosyl-Gly-Pro-Lys-NHNap and Bz-Arg-Gly-Arg-NHNap were 0.125, 0.5
      and 2.5 mM, respectively. The results obtained in this study suggest that the
      hatching enzyme from C. intestinalis exhibits both trypsin-like activity and
      metalloproteinase activity.

PMID- 9165106
TI  - Escape mutants of HIV-1 proteinase: enzymic efficiency and susceptibility to
      inhibition.
AB  - Genes encoding a number of mutants of HIV-1 proteinase were sub-cloned and
      expressed in E. coli. The proteinases containing mutations of single residues
      (e.g., G48V, V82F, I84V and L90M) were purified and their catalytic efficiencies
      relative to that of wild-type proteinase were examined using a polyprotein
      (recombinant HIV-1 gag) substrate and several series of synthetic peptides based
      on the -Hydrophobic * Hydrophobic-, -Aromatic * Pro- and pseudo-symmetrical types
      of cleavage junction. The L90M proteinase showed only small changes, whereas the
      activity of the other mutant enzymes was compromised more severely, particularly
      towards substrates of the -Aromatic * Pro- and pseudo-symmetrical types. The
      susceptibility of the mutants and the wild-type proteinase to inhibition by
      eleven different compounds was compared. The L90M proteinase again showed only
      marginal changes in its susceptibility to all except one of the inhibitors
      examined. The K(i) values determined for one inhibitor (Ro31-8959) showed that
      its potency towards the V82F, L90M, I84V and G48V mutant proteinases respectively
      was 2-, 3-, 17- and 27-fold less than against the wild-type proteinase. Several
      of the other inhibitors examined form a systematic series with Ro31-8959. The
      inhibition constants derived with these and a number of other inhibitors,
      including ABT-538 and L-735,524, are used in conjunction with the data on enzymic
      efficiency to assess whether each mutation in the proteinase confers an advantage
      for viral replication in the presence of any given inhibitor.

PMID- 9165107
TI  - Influence of actin binding on the conformation of the central segment of the
      heavy chain of skeletal myosin subfragment 1.
AB  - Chymotryptic subfragment 1 (S1) of fast skeletal muscle myosin was digested with
      trypsin in a low ionic strength buffer in the presence of actin. Under these
      conditions, leading to S1-induced polymerization of actin (Cooke, R. and Morales,
      M.F. (1971) J. Mol. Biol. 60, 249-261), the S1 heavy chain was cleaved between
      Lys-561 and Ser-562, generating the C-terminal fragment with apparent mass of 31
      kDa. In the absence of actin, this peptide bond was inaccessible to trypsin. The
      yield of the 31 kDa fragment decreased with the increase in the ionic strength of
      the medium. The cleavage was also partially inhibited by magnesium or calcium
      chloride at millimolar concentrations. The data suggest that in low salt
      conditions and at low concentrations of divalent cations, actin induces a
      conformational change in the C-terminal portion of the 50 kDa central segment of
      the S1 heavy chain.

PMID- 9165108
TI  - Structural and biochemical studies of alcohol dehydrogenase isozymes from
      Kluyveromyces lactis.
AB  - The cytosolic and mitochondrial alcohol dehydrogenases from Kluyveromyces lactis
      (KlADHs) were purified and characterised. Both the N-terminally blocked cytosolic
      isozymes, KlADH I and KlADH II, were strictly NAD-dependent and exhibited
      catalytic properties similar to those previously reported for other yeast ADHs.
      Conversely, the mitochondrial isozymes, KlADH III and KlADH IV, displayed Ala and
      Asn, respectively, as N-termini and were able to oxidise at an increased rate
      primary alcohols with aliphatic chains longer than ethanol, such as propanol,
      butanol, pentanol and hexanol. Interestingly, the mitochondrial KlADHs, at
      variance with cytosolic isozymes and the majority of ADHs from other sources,
      were capable of accepting as a cofactor, and in some case almost equally well,
      either NAD or NADP. Since Asp-223 of horse liver ADH, thought to be responsible
      for the selection of NAD as coenzyme, is strictly conserved in all the KlADH
      isozymes, this amino-acid residue should not be considered critical for the
      coenzyme discrimination with respect to the other residues lining the coenzyme
      binding pocket of the mitochondrial isozymes. The relatively low specificity of
      the mitochondrial KlADHs both toward the alcohols and the cofactor could be
      explained on the basis of an enhanced flexibility of the corresponding catalytic
      pockets. An involvement of the mitochondrial KlADH isozymes in the physiological
      reoxidation of the cytosolic NADPH was also hypothesized. Moreover, both
      cytosolic and KlADH IV isozymes have an additional cysteine, not involved in zinc
      binding, that could be responsible for the increased activity in the presence of
      2-mercaptoethanol.

PMID- 9165109
TI  - Acute inflammation, acute phase serum amyloid A and cholesterol metabolism in the
      mouse.
AB  - Acute inflammation results in a profound change in the apolipoprotein composition
      of high density lipoprotein (HDL). Several isoforms of the serum amyloid A (SAA)
      family, SAA1 and SAA2, become major components of HDL. This structural
      relationship has suggested that acute phase SAA plays some as yet unidentified
      role in HDL function, possibly related to cholesterol transport, during the
      course of acute inflammation. Using subcutaneous AgNO3 to induce a sterile
      abscess changes in plasma cholesterol and SAA were monitored over the subsequent
      144 h. Total plasma cholesterol began to increase within 12 h of the induction of
      inflammation and reached a peak in 24 h. Thereafter its plasma levels fell
      returning to normal values by 96-120 h. The bulk of the increase in plasma
      cholesterol was found in the free cholesterol fraction of HDL. This pattern of
      cholesterol increase corresponds to the established temporal changes for acute
      phase SAA (AP-SAA). AP-SAA levels increased within 8 h of the induction of
      inflammation and reached a peak at 24 h. They began to decrease by 48 h with
      small quantites still present 120 h later. In concert, but inversely, with the
      changes in AP-SAA the apoA-I, apoA-II, and apo-E, content of HDL decreased during
      the AP-SAA increases and increased as AP-SAA levels fell. The plasma appearance
      of cholesterol from the periphery, and central parts of the inflammatory site was
      assessed by the use of radiolabelled cholesterol. The peripherally placed
      cholesterol rapidly reached a peak plasma concentration within 24 h of injection.
      Cholesterol placed in the central part of the sterile abscess, a site relatively
      inaccessible to the vasculature required 48 h to reach its peak and was 5-times
      lower than that placed peripherally. The influence of AP-SAA on neutral
      cholesterol ester hydrolase (nCEH) activity in mouse liver homogenates, mouse
      peritoneal macrophage homogenates, and a purified porcine pancreatic enzyme with
      nCEH activity was also assessed. Following optimization with regard to pH, bile
      salt concentration, protein concentration and incubation time, mouse peritoneal
      macrophages had a significantly higher nCEH specific activity than that found in
      liver (7-8 fold). Purified AP-SAA, assessed over a concentration range of 0-10
      microg/ml, enhanced nCEH activity at concentrations above 2 microg/ml. The nCEH
      activity, regardless of its source, increased by 3-7 fold in the presence of AP
      SAA. Equivalent concentrations of apolipoprotein A-I (apo A-I) and bovine serum
      albumin (BSA) failed to alter the activity of nCEH. The effect of AP-SAA on a
      purified form of nCEH suggests that AP-SAA may have a direct effect on the
      activity of this enzyme. The temporal correlation of circulating AP-SAA and
      plasma cholesterol and the significant stimulation of nCEH by AP-SAA (but not
      apoA-I or BSA) provides further evidence that AP-SAA plays a role in cholesterol
      metabolism during the course of acute inflammation.

PMID- 9165110
TI  - Cooperativity: a unified view.
AB  - Cooperativity, the departure from hyperbolic behaviour of the fractional
      saturation of a receptor at equilibrium (Y) for different values of ligand
      concentration (L), is an essential property of many physiological mechanisms and
      a first clue to the existence of conformational transitions and allosteric
      interactions. Here we investigate the properties of a simple and sensitive
      procedure to test and quantify cooperative behaviour. The measure of
      cooperativity involved is kappa = dK(L)/dL where K(L) = (1- Y) L/Y= [free
      sites]L/[occupied sites] is called the 'global dissociation quotient' Cooperative
      behaviour appears when kappa is not equal to 0, i.e., K(L) is a function of L. We
      have shown, for several equilibrium models of cooperative behaviour (e.g., Monod
      Wyman-Changeux and Koshland-Nemethy-Filmer), that K(L) can be expressed as the
      weighted average of the microscopic dissociation constants (K(i)) where the
      weights are the corresponding fractions of occupied sites (X(i)), K(L)=
      sigmaK(i)X(i). As a consequence, the change in the global dissociation quotient
      with ligand concentration for a dimer is kappa = (K1 - K2)dX1/dL. This result
      shows that the quantitative importance of a cooperative behaviour in a dimer
      depends on two factors: (i) the difference of the microscopic dissociation
      constants of the sites and (ii) the change in the fraction of occupied sites with
      ligand concentration. We analyze the generality of this unified view concluding
      that it would be fulfilled by every equilibrium model where there is a one-to-one
      relationship between free and occupied sites.

PMID- 9165111
TI  - Reactivation strategies by unfolding/refolding of chymotrypsin derivatives after
      inactivation by organic solvents.
AB  - Immobilized enzyme derivatives, in organic media at neutral pH and moderate
      temperatures, should be mainly and perhaps uniquely inactivated by promotion of
      conformational changes on their 3D structure. Subsequent irreversible
      inactivation mechanisms (intermolecular aggregations, chemical modifications,
      thiol-disulfide exchanges) are thus impossible. However, simple reincubation in
      aqueous medium of enzymes previously inactivated by solvents usually yields
      significant but slow and incomplete reactivations. Disruption of incorrect
      protein structures by denaturing agents (urea, guanidine) is proposed as a new
      strategy to get rapid, complete and technologically feasible reactivations. By
      using multipoint immobilized chymotrypsin derivatives, we have evaluated the
      possibility of unfolding and further refolding of native (non-inactivated)
      derivatives by different denaturing conditions. After unfolding in 8 M guanidine,
      derivatives were quickly and completely refolded up to 100% of catalytic activity
      in 10 minutes. Besides, successive cycles of unfolding and refolding could be
      exactly reproduced. Finally we checked the possibility to reactivate chymotrypsin
      derivatives inactivated by dioxane. Simple reincubations in aqueous media yielded
      a poor reactivation even after 24 hours. However, unfolding in 8 M guanidine
      enabled complete reactivation in less than 2 hours. From this point of view, by
      working under 'chemically inert conditions' (moderate pH and temperatures), fully
      dispersed covalently immobilized enzyme derivatives seem to behave as almost
      everlasting catalysts despite the very deleterious effect of organic media.

PMID- 9165112
TI  - The allocation of epiblast cells to the embryonic heart and other mesodermal
      lineages: the role of ingression and tissue movement during gastrulation.
AB  - The cardiogenic potency of cells in the epiblast of the early primitive-streak
      stage (early PS) embryo was tested by heterotopic transplantation. The results of
      this study show that cells in the anterior and posterior epiblast of the early PS
      stage embryos have similar cardiogenic potency, and that they differentiated to
      heart cells after they were transplanted directly to the heart field of the late
      PS embryo. That the epiblast cells can acquire a cardiac fate without any prior
      act of ingression through the primitive streak or movement within the mesoderm
      suggests that neither morphogenetic event is critical for the specification of
      the cardiogenic fate. The mesodermal cells that have recently ingressed through
      the primitive streak can express a broad cell fate that is characteristic of the
      pre-ingressed cells in the host when they were returned to the epiblast. However,
      mesoderm cells that have ingressed through the primitive streak did not
      contribute to the lateral plate mesoderm after transplantation back to the
      epiblast, implying that some restriction of lineage potency may have occurred
      during ingression. Early PS stage epiblast cells that were transplanted to the
      epiblast of the mid PS host embryos colonised the embryonic mesoderm but not the
      extraembryonic mesoderm. This departure from the normal cell fate indicates that
      the allocation of epiblast cells to the mesodermal lineages is dependent on the
      timing of their recruitment to the primitive streak and the morphogenetic options
      that are available to the ingressing cells at that instance.

PMID- 9165113
TI  - Retinoid signaling is required for the establishment of a ZPA and for the
      expression of Hoxb-8, a mediator of ZPA formation.
AB  - We show that retinoid receptor antagonists applied to the presumptive wing region
      block the formation of a zone of polarizing activity (ZPA). This suggests a
      direct relationship between retinoid signaling and the establishment of the ZPA.
      We provide evidence that the Hox gene, Hoxb-8, is a direct target of retinoid
      signaling since exogenously applied RA rapidly induces this gene in the absence
      of protein synthesis and, moreover, retinoid receptor antagonists down-regulate
      Hoxb-8 expression. In addition, we find that, in the lateral plate mesoderm, the
      domains of Hoxb-8 expression and of polarizing activity are coextensive. Taken
      together, these findings support the hypothesis that retinoids are required for
      the establishment of a ZPA, and that retinoids act, at least in part, through
      Hoxb-8, a gene associated with ZPA formation (Charite et al., 1994).

PMID- 9165115
TI  - A new rhodopsin in R8 photoreceptors of Drosophila: evidence for coordinate
      expression with Rh3 in R7 cells.
AB  - The photoreceptor cells of the Drosophila compound eye are precisely organized in
      elementary units called ommatidia. The outer (R1-R6) and inner (R7, R8)
      photoreceptors represent two physiologically distinct systems with two different
      projection targets in the brain (for review see Hardie, 1985). All cells of the
      primary system, R1-R6, express the same rhodopsin and are functionally identical.
      In contrast, the R7 and R8 photoreceptors are different from each other. They
      occupy anatomically precise positions, with R7 on top of R8. In fact, there are
      several classes of R7/R8 pairs, which differ morphologically and functionally and
      are characterized by the expression of one of two R7-specific opsins, rh3 or rh4.
      Here, we describe the identification of a new opsin gene, rhodopsin 5, expressed
      in one subclass of R8 cells. Interestingly, this subclass represents R8 cells
      that are directly underneath the R7 photoreceptors expressing rh3, but are never
      under those expressing rh4. These results confirm the existence of two
      subpopulations of R7 and R8 cells, which coordinate the expression of their
      respective rh genes. Thus, developmental signaling pathways between R7 and R8
      lead to the exclusive expression of a single rhodopsin gene per cell and to the
      coordinate expression of another one in the neighboring cell. Consistent with
      this, rh5 expression in R8 disappears when R7 cells are absent (in sevenless
      mutant). We propose a model for the concerted evolution of opsin genes and the
      elaboration of the architecture of the retina.

PMID- 9165114
TI  - Defects of urogenital development in mice lacking Emx2.
AB  - The homeobox gene Emx2 is a mouse homologue of a Drosophila head gap gene empty
      spiracles (ems) and is essential for the development of dorsal telencephalon
      (Yoshida, M., Suda, Y., Matsuo, I., Miyamoto, N., Takeda, N., Kuratani, S. and
      Aizawa, S. (1997) Development 124, 101-111). At the same time, Emx2 is expressed
      in the epithelial components of the developing urogenital system and, in Emx2
      mutant mice, the kidneys, ureters, gonads and genital tracts were completely
      missing. Pax-2 and c-ret expressions in the Wolffian duct and WT-1 and GDNF
      expressions in the metanephric blastema were initially normal in the mutant. The
      ureteric bud grew and invaded the metanephric mesenchyme where Pax-2 expression
      was normally induced. Subsequently, however, Pax-2, c-ret and Lim1 expressions in
      the ureteric bud and GDNF expression in the mesenchyme were greatly reduced. Wnt
      4 expression was never found in the mesenchyme. The tip of the ureteric bud never
      dilated and branching of the bud did not occur. Neither pretubular cell
      aggregates nor epithelialization were found in the mesenchyme. Instead the
      ureteric bud soon degenerated and apoptotic figures were prominent in mesenchymal
      cells. In explant culture, the mutant ureteric bud did not induce the epithelial
      transformation of the wild-type mesenchyme, and branching of the mutant ureteric
      bud was not induced by wild-type mesenchyme. In contrast, defects were not
      apparent in the mutant mesenchyme by co-culture with wild-type ureteric bud or
      spinal cord. These results suggest that, in metanephrogenesis, Emx2 is essential
      for the ureteric bud functions subsequent to Pax-2 induction in the metanephric
      mesenchyme. Degeneration of the Wolffian duct and mesonephric tubules was also
      abnormally accelerated without the formation of the Mullerian duct.

PMID- 9165116
TI  - Requirement for engrailed and invected genes reveals novel regulatory
      interactions between engrailed/invected, patched, gooseberry and wingless during
      Drosophila neurogenesis.
AB  - During neurogenesis, the transmembrane protein Patched (Ptc) promotes a wingless
      (wg)-mediated specification of a neuronal precursor cell, NB4-2, by repressing
      gooseberry (gsb). In this study, novel interactions of these genes with engrailed
      (en) and invected (inv) during neurogenesis have been uncovered. While in row 4
      cells Ptc represses gsb and wg, in row 5 cells en/inv relieve Ptc repression of
      gsb by a non-autonomous mechanism that does not involve hedgehog (hh). This
      differential regulation of gsb leads to the specification of NB5-3 and NB4-2
      identities to two distinct neuroblasts. The uncoupling of the ptc-gsb regulatory
      circuit also enables gsb to promote Wg expression in row 5 cells. Our results
      suggest that the en/inv-->ptc-->gsb-->wg pathway uncovered here and the hh-->wg
      are distinct pathways that function to maintain wild-type level of Wg. Our
      results also indicate that Hh is not the only ligand for Ptc and similarly Ptc is
      not the only receptor for Hh.

PMID- 9165117
TI  - A vegetally localized T-box transcription factor in Xenopus eggs specifies
      mesoderm and endoderm and is essential for embryonic mesoderm formation.
AB  - Pattern formation in early embryogenesis is guided by maternal, localized
      determinants and by inductive interactions between cells. In Xenopus eggs,
      localized molecules have been identified and some, such as Vg1 and Xwnt-11, can
      specify cell fates by functioning as inducers or patterning agents. We have used
      differential screening to identify new Xenopus genes that regulate mesodermal
      patterning, and we have isolated a new member of the T-box family of
      transcription factors. This gene, named Brat, is expressed maternally and its
      transcripts are localized to the vegetal hemisphere of the egg. During early
      embryonic cleavage, Brat mRNA becomes partitioned primarily within vegetal cells
      that are fated to form the endoderm. Zygotic expression of Brat begins at the
      onset of gastrulation within the presumptive mesoderm of the marginal zone.
      Consistent with its zygotic expression pattern, Brat induces, in a dose-dependent
      manner, a full spectrum of mesodermal genes that mark tissues across the dorsal
      ventral axis, from the blood through the Spemann organizer. Brat also induces
      endoderm, consistent with its vegetal localization, making Brat a good candidate
      for a maternal determinant of the endoderm. We tested whether endogenous Brat is
      required for mesoderm formation by expressing a dominant-negative,
      transcriptional repressor form of Brat in embryos. This treatment inhibited
      mesoderm formation and severely disrupted normal development, thereby
      establishing that Brat plays a critical role in embryonic mesoderm formation and
      body patterning.

PMID- 9165118
TI  - The Groucho-like transcription factor UNC-37 functions with the neural
      specificity gene unc-4 to govern motor neuron identity in C. elegans.
AB  - Groucho and Tup1 are members of a conserved family of WD repeat proteins that
      interact with specific transcription factors to repress target genes. Here we
      show that mutations in WD domains of the Groucho-like protein, UNC-37, affect a
      motor neuron trait that also depends on UNC-4, a homeodomain protein that
      controls neuronal specificity in Caenorhabditis elegans. In unc-4 mutants, VA
      motor neurons assume the pattern of synaptic input normally reserved for their
      lineal sister cells, the VB motor neurons; the loss of normal input to the VAs
      produces a distinctive backward movement defect. Substitution of a conserved
      residue (H to Y) in the fifth WD repeat in unc-37(e262) phenocopies the Unc-4
      movement defect. Conversely, an amino acid change (E to K) in the sixth WD repeat
      of UNC-37 is a strong suppressor of unc-37(e262) and of specific unc-4 missense
      mutations. We have previously shown that UNC-4 expression in the VA motor neurons
      specifies the wild-type pattern of presynaptic input. Here we demonstrate that
      UNC-37 is also expressed in the VAs and that unc-37 activity in these neurons is
      sufficient to restore normal movement to unc-37(e262) animals. We propose that
      UNC-37 and UNC-4 function together to prevent expression of genes that define the
      VB pattern of synaptic inputs and thereby generate connections specific to the VA
      motor neurons. In addition, we show that the WD repeat domains of UNC-37 and of
      the human homolog, TLE1, are functionally interchangeable in VA motor neurons
      which suggests that this highly conserved protein domain may also specify motor
      neuron identity and synaptic choice in more complex nervous systems.

PMID- 9165119
TI  - The single MyoD family gene of Ciona intestinalis encodes two differentially
      expressed proteins: implications for the evolution of chordate muscle gene
      regulation.
AB  - A MyoD family gene was identified in the ascidian Ciona intestinalis and
      designated CiMDF (Ciona intestinalis Muscle Determination Factor). Expression of
      CiMDF was restricted to the muscle cells of the developing embryo and the body
      wall muscle of adults. Northern blots showed that two differentially regulated
      CiMDF transcripts were expressed during development. A 1.8 kb transcript (CiMDFa)
      appeared first and was gradually replaced by a 2.7 kb transcript (CiMDFb). These
      transcripts encoded essentially identical MyoD family proteins with the exception
      of a 68 amino acid C-terminal sequence present in CiMDFb that was absent from
      CiMDFa. Although both CiMDFa and CiMDFb contained the cysteine-rich/basic-helix
      loop helix domain (Cys-rich/bHLH) present in all MyoD family proteins, only
      CiMDFb contained the region near the C terminus (Domain III) characteristic of
      this gene family. Genomic Southern blots showed that C. intestinalis has only one
      MyoD family gene, suggesting that CiMDFa and CiMDFb result from differential
      processing of primary transcripts. The existence of two MyoD family proteins that
      are differentially expressed during ascidian embryogenesis has novel parallels to
      vertebrate muscle development and may reflect conserved myogenic regulatory
      mechanisms among chordates.

PMID- 9165120
TI  - Sequence and embryonic expression of the amphioxus engrailed gene (AmphiEn): the
      metameric pattern of transcription resembles that of its segment-polarity homolog
      in Drosophila.
AB  - Vertebrate segmentation has been proposed as an evolutionary inheritance either
      from some metameric protostome or from a more closely related deuterostome. To
      address this question, we studied the developmental expression of AmphiEn, the
      engrailed gene of amphioxus, the closest living invertebrate relative of the
      vertebrates. In neurula embryos of amphioxus, AmphiEn is expressed along the
      anteroposterior axis as metameric stripes, each located in the posterior part of
      a nascent or newly formed segment. This pattern resembles the expression stripes
      of the segment-polarity gene engrailed, which has a key role in establishing and
      maintaining the metameres in embryos of Drosophila and other metameric
      protostomes. Later, amphioxus embryos express AmphiEn in non-metameric patterns -
      transiently in the embryonic ectoderm and dorsal nerve cord. Nerve cord
      expression occurs in a few cells approximately midway along the rostrocaudal axis
      and also in a conspicuous group of anterior cells in the cerebral vesicle at a
      level previously identified as corresponding to the vertebrate diencephalon.
      Compared to vertebrate engrailed expression at the midbrain/hindbrain boundary,
      AmphiEn expression in the cerebral vesicle is relatively late. Thus, it is
      uncertain whether the cerebral vesicle expression marks the rostral end of the
      amphioxus hindbrain; if it does, then amphioxus may have little or no homolog of
      the vertebrate midbrain. The segmental expression of AmphiEn in forming somites
      suggests that the functions of engrailed homologs in establishing and maintaining
      a metameric body plan may have arisen only once during animal evolution. If so,
      the protostomes and deuterostomes probably shared a common segmented ancestor.

PMID- 9165121
TI  - Activating and repressing signals in head development: the role of Xotx1 and
      Xotx2.
AB  - Xotx1 and Xotx2 are two Xenopus homologues of the Drosophila orthodenticle gene
      that are specifically expressed in presumptive head regions that do not undergo
      convergent extension movements during gastrulation. We studied the function of
      Xotx1 and compared it with that of Xotx2. Ectopic expression of each of the two
      genes has similar effects in impairing trunk and tail development. Experimental
      evidence suggests that posterior deficiencies observed in microinjected embryos
      are due to negative interference with convergent extension movements.
      Transplantations of putative tail-forming regions showed that, while Xotx1
      overexpression inhibits tail organizer activity, Xotx2 overexpression is able to
      turn a tail organizer into a head organizer. Finally, Xotx1 and Xotx2 are
      activated by factors involved in head formation and repressed by a posteriorizing
      signal like retinoic acid. Taken together, these data suggest that Xotx genes are
      involved in head-organizing activity. They also suggest that the head organizer
      may act not only stimulating the formation of anterior regions, but also
      repressing the formation of posterior structures.

PMID- 9165122
TI  - 5-HT2B receptor-mediated serotonin morphogenetic functions in mouse cranial
      neural crest and myocardiac cells.
AB  - During embryogenesis, serotonin has been reported to be involved in craniofacial
      and cardiovascular morphogenesis. The detailed molecular mechanisms underlying
      these functions, however remain unknown. From mouse and human species, we have
      recently reported the cloning of 5-HT2B receptors which share signal transduction
      pathways with other 5-HT2 receptor subtypes (5-HT2A and 5-HT2C). In addition to
      phospholipase C stimulation, it appears that these three subtypes of receptor
      transduce a common serotonin-induced mitogenic activity, which could be important
      for cell differentiation and proliferation. We have first investigated the
      expression of 5-HT2 receptor mRNAs in the mouse embryo. Interestingly, a peak of
      5-HT2B receptor mRNA expression was detected 8-9 days postcoitum, whereas there
      was only low level 5-HT2A and no 5-HT2C receptor mRNA expression at this stage.
      Expression of this receptor was confirmed by binding assays using a 5-HT2
      specific ligand which revealed a peak of binding to membrane preparations from 9
      days postcoitum embryos. In addition, whole mount in situ hybridisation and
      immunohistochemistry on similar stage embryos detected 5-HT2B expression in
      neural crest cells, heart myocardium and somites. The requirement for functional
      5-HT2B receptors between 8 and 9 days postcoitum is supported by culture of
      embryos exposed to 5-HT2-specific ligands; 5-HT2B high-affinity antagonist such
      as ritanserin, induced morphological defects in the cephalic region, heart and
      neural tube. These antagonistic treatments interfere with cranial neural crest
      cell migration, induce their apoptosis, and are responsible for abnormal
      sarcomeric organisation of the subepicardial layer and for the absence of the
      trabecular cell layer in the ventricular myocardium. This report indicates for
      the first time that 5-HT2B receptors are actively mediating the action of
      serotonin on embryonic morphogenesis, probably by preventing the differentiation
      of cranial neural crest cells and myocardial precursor cells.

PMID- 9165123
TI  - Coordination of larval and prepupal gene expression by the DHR3 orphan receptor
      during Drosophila metamorphosis.
AB  - The DHR3 orphan receptor gene is induced directly by the steroid hormone ecdysone
      at the onset of Drosophila metamorphosis. DHR3 expression peaks in early
      prepupae, as the early puff genes are repressed and betaFTZ-F1 is induced. Here
      we provide evidence that DHR3 directly contributes to both of these regulatory
      responses. DHR3 protein is bound to many ecdysone-induced puffs in the polytene
      chromosomes, including the early puffs that encode the BR-C and E74 regulatory
      genes, as well as the E75, E78 and betaFTZ-F1 orphan receptor loci. Three DHR3
      binding sites were identified downstream from the start site of betaFTZ-F1
      transcription, further indicating that this gene is a direct target of DHR3
      regulation. Ectopic expression of DHR3 revealed that the polytene chromosome
      binding pattern is of functional significance. DHR3 is sufficient to repress BR
      C, E74A, E75A and E78B transcription as well as induce betaFTZ-F1. DHR3 thus
      appears to function as a switch that defines the larval-prepupal transition by
      arresting the early regulatory response to ecdysone at puparium formation and
      facilitating the induction of the betaFTZ-F1 competence factor in mid-prepupae.
      This study also provides evidence for direct cross-regulation among orphan
      members of the nuclear receptor superfamily and further implicates these genes as
      critical transducers of the hormonal signal during the onset of Drosophila
      metamorphosis.

PMID- 9165124
TI  - A nanos homolog in leech.
AB  - From the glossiphoniid leech Helobdella robusta, we have cloned and determined
      the complete coding sequence of Hro-nos, a gene homologous to the nanos gene from
      Drosophila melanogaster. Developmental northern blots show that Hro-nos, like
      nanos, is a maternal transcript that decays rapidly during early development. A
      polyclonal antiserum raised against the HRO-NOS protein was used in developmental
      western blots and for immunostaining leech embryos of different developmental
      stages. The HRO-NOS protein is first detectable in 2-cell embryos (4-6 hours of
      development) and exhibits a transient expression peaking during fourth cleavage
      (9-12 cells; 8-14 hours of development). The HRO-NOS protein exhibits a graded
      distribution along the primary embryonic axis and is partitioned unequally
      between the sister cells DNOPQ and DM, progeny of macromere D' at fourth
      cleavage: DNOPQ is the segmental ectoderm precursor cell and exhibits levels of
      HRO-NOS protein that are at least two-fold higher than in cell DM, the segmental
      mesoderm precursor cell. The observed expression pattern suggests that Hro-nos
      plays a role in the decision between ectodermal and mesodermal cell fates in
      leech.

PMID- 9165125
TI  - Ethylene provides positional information on cortical cell division but is not
      involved in Nod factor-induced root hair tip growth in Rhizobium-legume
      interaction.
AB  - Nod factors secreted by Rhizobium leguminosarum bv. viciae induce root hair
      deformation, involving a reinitiation of tip growth, and the formation of nodule
      primordia in Vicia sativa (vetch). Ethylene is a potent inhibitor of cortical
      cell division, an effect that can be counteracted by applying silver ions (Ag+)
      or aminoethoxy-vinylglycine (AVG). In contrast to the inhibitory effect on
      cortical cell division, ethylene promotes the formation of root hairs (which
      involves tip growth) in the root epidermis of Arabidopsis. We investigate the
      possible paradox concerning the action of ethylene, putatively promoting Nod
      factor induced tip growth whilst, at the same time, inhibiting cortical cell
      division. We show, by using the ethylene inhibitors AVG and Ag+, that ethylene
      has no role in the reinitiation of root hair tip growth induced by Nod factors
      (root hair deformation) in vetch. However, root hair formation is controlled, at
      least in part, by ethylene. Furthermore, we show that ACC oxidase, which
      catalizes the last step in ethylene biosynthesis, is expressed in the cell layers
      opposite the phloem in that part of the root where nodule primordia are induced
      upon inoculation with Rhizobium. Therefore, we test whether endogenously produced
      ethylene provides positional information controlling the site where nodule
      primordia are formed by determining the position of nodules formed on pea roots
      grown in the presence of AVG or Ag+.

PMID- 9165126
TI  - Structural and genetic analysis of epidermal cell differentiation in Arabidopsis
      primary roots.
AB  - In a screen designed to identify genes in the specification of epidermal cell
      fate in Arabidopsis primary roots we have isolated 8 new mutants that fall into 6
      complementation groups corresponding to the 'root hairless' genes RHL1, RHL2 and
      RHL3 and the 'ectopic root hair' genes ERH1, ERH2 and ERH3. The erh2 mutant is
      allelic to pom1, a conditional root expansion mutant, and reveals a possible link
      between epidermal root hair initiation and radial cell expansion. Apart from erh1
      the mutants also show defects in shoot development, indicating a complex role for
      the affected genes. Mutant phenotypes in the patterning and shape of leaf
      trichomes in rhl1, rhl2, rhl3 and erh3 were particularly obvious. The root
      hairless mutants are only partly responsive to increased ethylene concentrations,
      while the ectopic root hair mutants are fully responsive to reduced
      concentrations of ethylene, a permissive regulator of root hair initiation. This
      result and the analysis of double mutants suggest a complex pathway leading to
      root hair initiation that requires the RHL and ERH genes for correct
      differentiation.

PMID- 9165128
TI  - In situ dissection of the Fab-7 region of the bithorax complex into a chromatin
      domain boundary and a Polycomb-response element.
AB  - Parasegmental (PS)-specific expression of the homeotic genes of the bithorax
      complex (BX-C) appears to depend upon the subdivision of the complex into a
      series of functionally independent cis-regulatory domains. Fab-7 is a regulatory
      element that lies between iab-6 and iab-7 (the PS11- and PS12-specific cis
      regulatory domains, respectively). Deletion of Fab-7 causes ectopic expression of
      iab-7 in PS11 (where normally only iab-6 is active). Two models have been
      proposed to account for the dominant Fab-7 phenotype. The first considers that
      Fab-7 functions as a boundary element that insulates iab-6 and iab-7. The second
      model envisages that Fab-7 contains a silencer element that keeps iab-7 repressed
      in parasegments anterior to PS12. Using a P-element inserted in the middle of the
      Fab-7 region (the bit transposon), we have generated an extensive collection of
      new Fab-7 mutations that allow us to subdivide Fab-7 into a boundary element and
      a Polycomb-respond element (PRE). The boundary lies within 1 kb of DNA on the
      proximal side of the bit transposon (towards iab-6). Deletions removing this
      element alone cause a complex gain- and loss-of-function phenotype in PS11; in
      some groups of cells, both iab-6 and iab-7 are active, while in others both iab-6
      and iab-7 are inactive. Thus, deletion of the boundary allows activating as well
      as repressing activities to travel between iab-6 and iab-7. We also provide
      evidences that the boundary region contains an enhancer blocker element. The
      Polycomb-response element lies within 0.5 kb of DNA immediately distal to the
      boundary (towards iab-7). Deletions removing the PRE alone do not typically cause
      any visible phenotype as homozygotes. Interestingly, weak ectopic activation of
      iab-7 is observed in hemizygous PRE deletions, suggesting that the mechanisms
      that keep iab-7 repressed in the absence of this element may depend upon
      chromosome pairing. These results help to reconcile the previously contradictory
      models on Fab-7 function and to shed light on how a chromatin domain boundary and
      a nearby PRE concur in the setting up of the appropriate PS-specific expression
      of the Abd-B gene of the BX-C.

PMID- 9165127
TI  - The nuclear receptor SF-1 mediates sexually dimorphic expression of Mullerian
      Inhibiting Substance, in vivo.
AB  - Mullerian Inhibiting Substance (MIS) functions to promote regression of the
      Mullerian duct during male development. Maintaining the sexually dimorphic
      pattern of MIS expression is essential for proper mammalian reproductive tract
      development. Here, we show that the intricate spatial and temporal pattern of MIS
      expression is directed by a remarkably small proximal promoter of only 180 base
      pairs in length. Expression of the MIS-human growth hormone transgene (MIS/GH) is
      restricted to Sertoli cells in embryonic testis and to granulosa cells of
      postnatal ovary, consistent with the known MIS expression pattern. The proximal
      MIS promoter is therefore sufficient to direct the initiation and the maintenance
      of MIS gene expression in both sexes. Moreover, in vivo MIS promoter activity
      requires an intact binding site for the orphan nuclear receptor SF-1. Taken
      together, these data strongly suggest that SF-1 directly activates MIS in
      embryonic and postnatal gonads. Consistent with the proposed role of SF-1 in
      mammalian sex-determination, our study provides physiological evidence that a SF
      1 binding site is essential for gene activation of an embryonic testis-specific
      marker.

PMID- 9165130
TI  - Genes necessary for C. elegans cell and growth cone migrations.
AB  - The migrations of cells and growth cones contribute to form and pattern during
      metazoan development. To study the mechanisms that regulate cell motility, we
      have screened for C. elegans mutants defective in the posteriorly directed
      migrations of the canal-associated neurons (CANs). Here we describe 14 genes
      necessary for CAN cell migration. Our characterization of the mutants has led to
      three conclusions. First, the mutations define three gene classes: genes
      necessary for cell fate specification, genes necessary for multiple cell
      migrations and a single gene necessary for final positioning of migrating cells.
      Second, cell interactions between the CAN and HSN, a neuron that migrates
      anteriorly to a position adjacent to the CAN, control the final destination of
      the HSN cell body. Third, C. elegans larval development requires the CANs. In the
      absence of CAN function, larvae arrest development, with excess fluid
      accumulating in their pseudocoeloms. This phenotype may reflect a role of the
      CANs in osmoregulation.

PMID- 9165129
TI  - Slug, a zinc finger gene previously implicated in the early patterning of the
      mesoderm and the neural crest, is also involved in chick limb development.
AB  - The great advances made over the last few years in the identification of
      signalling molecules that pattern the limb bud along the three axes make the limb
      an excellent model system with which to study developmental mechanisms in
      vertebrates. The understanding of the signalling networks and their mutual
      interactions during limb development requires the characterisation of the
      corresponding downstream genes. In this study we report the expression pattern of
      Slug, a zinc-finger-containing gene of the snail family, during the development
      of the limb, and its regulation by distinct axial signalling systems. Slug
      expression is highly dynamic, and at different stages of limb development can be
      correlated with the zone of polarizing activity, the progress zone and the
      interdigital areas. We show that the maintenance of its expression is dependent
      on signals from the apical ectodermal ridge and independent of Sonic Hedgehog. We
      also report that, in the interdigit, apoptotic cells lie outside of the domains
      of Slug expression. The correlation of Slug expression with areas of
      undifferentiated mesenchyme at stages of tissue differentiation is consistent
      with its role in early development, in maintaining the mesenchymal phenotype and
      repressing differentiation processes. We suggest that Slug is involved in the
      epithelial-mesenchymal interactions that lead to the maintenance of the progress
      zone.

PMID- 9165131
TI  - Cortical granules of the sea urchin translocate early in oocyte maturation.
AB  - Cortical granules are secretory vesicles poised at the cortex of an egg that,
      upon stimulation by sperm contact at fertilization, secrete their contents. These
      contents modify the extracellular environment and block additional sperm from
      reaching the egg. The role of cortical granules in blocking polyspermy is
      conserved throughout much of phylogeny. In the sea urchin, cortical granules
      accumulate throughout the cytoplasm during oogenesis, but in mature eggs the
      cortical granules are attached to the plasma membrane, having translocated to the
      cortex at some earlier time. To study the process of cortical granule
      translocation to the cell surface we have devised a procedure for maturation of
      sea urchin oocytes in vitro. Using this procedure, we examined the rate of oocyte
      maturation by observing the movement and breakdown of the germinal vesicle, the
      formation of polar bodies and the formation of the egg pronucleus. We find that
      oocyte maturation takes approximately 9 hours in the species used here
      (Lytechinus variegatus), from the earliest indication of maturation (germinal
      vesicle movement) to formation of a distinct pronucleus. We then observed the
      translocation of cortical granules in these cells by immunolocalization using a
      monoclonal antibody to hyalin, a protein packaged specifically in cortical
      granules. We found that the translocation of cortical granules in in vitro
      matured oocytes begins with the movement of the germinal vesicle to the oocyte
      cell surface, and is 50% complete 1 hour after germinal vesicle breakdown. In the
      in vitro-matured egg, 99% of the cortical granules are at the cortex,
      indistinguishable from translocation in oocytes that mature in vivo. We have also
      found that eggs that mature in vitro are functionally identical to eggs that
      mature in vivo by four criteria. (1) The matured cells undergo a selective
      turnover of mRNA encoding cortical granule contents. (2) The newly formed
      pronucleus begins transcription of histone messages. (3) Cortical granules that
      translocate in vitro are capable of exocytosis upon activation by the calcium
      ionophore, A23187. (4) The mature egg is fertilizable and undergoes normal
      cleavage and development. In vitro oocyte maturation enables us to examine the
      mechanism of cortical granule translocation and other processes that had
      previously only been observed in static sections of fixed ovaries.

PMID- 9165132
TI  - Hyperfractionation: where do we stand?
AB  - Hyperfractionation is generally expected to allow an escalation of total dose,
      thereby increasing tumour control rate, without increasing the risk of late
      complications. The purpose of this review is to assess the empirical evidence for
      this therapeutic gain from hyperfractionated radiotherapy. Although extensive
      clinical data have been accumulated until now, especially on treatment of head
      and neck cancer, the line of evidence is not consistent. The present analysis
      indicates that the dose per fraction generally used in standard radiotherapy is
      already a good choice.

PMID- 9165133
TI  - Neoadjuvant chemotherapy with cisplatin and 5-fluorouracil in advanced squamous
      cell carcinoma of the head and neck: a randomized phase III study.
AB  - BACKGROUND AND PURPOSE: In 1986 a prospective, randomized, multi-centre trial for
      evaluation of neoadjuvant chemotherapy with cisplatin and 5-fluorouracil in the
      treatment of advanced squamous cell carcinoma of the head and neck was initiated.
      As survival in this group of patients is poor the purpose was to find a possible
      survival benefit of the chemotherapy in addition to radiotherapy compared to
      radiotherapy only. METHODS: Four-hundred sixty-one patients from Denmark, Norway
      and Sweden with tumors in oral cavity, oropharynx, hypopharynx and larynx were
      randomized to receive either standard treatment (radiotherapy or radiotherapy
      followed by surgery) or neoadjuvant chemotherapy followed by standard treatment.
      Chemotherapy included three courses of cisplatin 100 mg/m2 i.v. infusion on day 1
      followed by 5-fluorouracil 1000 mg/m2 per day continuous i.v. infusion for 120
      hours. Radiotherapy 64-70 Gy in 2 Gy per fraction, 5 times/week, was given to
      patients in both treatment arms. RESULTS: Response rate was 71% for patients
      randomized to chemotherapy-radiotherapy and 66% for patients randomized to
      standard treatment (not statistically significant). Residual tumors were excised
      if possible. After surgery 62% of the patients randomized to chemotherapy
      radiotherapy and 60% of the patients in the standard treatment group were
      clinically tumor free. CONCLUSIONS: No statistically significant benefit in
      survival was observed for patients treated with neoadjuvant chemotherapy followed
      by radiotherapy. Nor was there any impact of chemotherapy on the number of
      patients achieving loco-regional tumor control after primary treatment.

PMID- 9165134
TI  - Radiation therapy alone or with concurrent low-dose daily either cisplatin or
      carboplatin in locally advanced unresectable squamous cell carcinoma of the head
      and neck: a prospective randomized trial.
AB  - Between January 1988 and December 1991, 159 patients with Stage III/IV (M0)
      squamous cell carcinoma of the head and neck were randomized to receive standard
      fraction RT (70 Gy) (group I) or the same RT plus either 6 mg/m2 of cisplatin
      (CDPP) (group II) or 25 mg/ m2 of carboplatin (CBDCA) both given daily during RT
      (group III). Patients in groups II and III had significantly higher overall
      response rates then those in group I (P = 0.011 and P = 0.0025, respectively)
      with no difference between groups II and III (P = 0.60). They also had
      significantly longer median survival time (MST) and higher 5-year survival rates
      than those in group I (MST, 32 months (32%) and 30 months (29%) versus 16 months
      (15%), respectively; P = 0.011 and P = 0.019, respectively), with no difference
      between the two RT/CHT groups. Median time to local recurrence (MTLR) and 5-year
      local recurrence-free survival (LRFS) were significantly higher for both RT/CHT
      when compared to RT alone (MTLR, not attained yet and 30 months versus 10 months,
      respectively; 5-year LRFS, 51% and 48% versus 27%, respectively; P = 0.018 and P
      = 0.040, respectively) with no difference between the two RT/CHT groups. There
      was no difference between the three treatment groups regarding regional lymph
      node and distant metastasis control. Apart from acute high grade (> or =3)
      hematological toxicity that was significantly more frequent in the two RT/CHT
      groups and no different between the two RT/CHT groups, other acute high grade
      toxicity was similar between the three treatment groups. Late high grade toxicity
      was infrequent and similar between the three treatment groups.

PMID- 9165135
TI  - A randomised trial of accelerated versus conventional radiotherapy in head and
      neck cancer.
AB  - BACKGROUND AND PURPOSE: To study the effect of accelerated radiation treatment in
      locally advanced head and neck cancer, a prospective randomised trial was
      conducted comparing two fractionation schemes which differed only in the overall
      treatment time; fraction size and total dose were the same in both arms.
      MATERIALS AND METHODS: Eighty-two patients with stage 3 or 4 squamous cell cancer
      of the oral cavity, oropharynx, hypopharynx or larynx considered suitable for
      radical radiotherapy as primary treatment were stratified by site and stage and
      randomised to receive 66 Gy in 33 2 Gy daily fractions in 45-48 days (o.d.) or 66
      Gy in 33 2 Gy twice daily fractions in 22-25 days (b.i.d.). RESULTS: An initial
      improved clinical response in tumour control in the b.i.d. arm was not sustained
      and the 3 year recurrence free survival and overall survival rates were similar
      and not significantly different. The actuarial recurrence free survival was 49.1%
      in the b.i.d. arm and 44.3% in the o.d. arm. The disease free 3 year survival was
      59.4% and 56.8%, respectively. The acute and late normal tissue effects were
      scored using the RTOG scale. As expected the acute effects were much greater in
      the b.i.d. arm. The combined grade 3 and 4 late effects were similar but the
      proportion of grade 4 reactions was significantly higher in the b.i.d. arm. The
      increase in grade 4 toxicity caused the trial to be discontinued after 82 of the
      planned 226 patients had been randomised. CONCLUSIONS: The severity of the normal
      tissue effects and a failure to demonstrate sustained local control does not
      support this fractionation scheme in patients with such extensive head and neck
      cancer.

PMID- 9165136
TI  - Importance of overall treatment time for the outcome of radiotherapy of advanced
      head and neck carcinoma: dependency on tumor differentiation.
AB  - PURPOSE: Accelerated repopulation of tumor cells during radiotherapy has been
      suggested as an important cause of treatment failure in squamous cell carcinoma
      of the head and neck. Due to tumor heterogeneity, not all tumors may benefit from
      accelerated radiotherapy at the expense of a lower total dose. This analysis
      evaluates the impact of histological differentiation on loco-regional control in
      relation to treatment duration. PATIENTS AND METHODS: A total of 501 patients
      with advanced supraglottic and pharyngeal squamous cell carcinoma with known
      histopathological grading were treated with planned split-course (191 patients)
      or continuous radiotherapy (310 patients) in two consecutive randomized
      controlled trials. Irradiation was given 2 Gy per fraction, 5 fractions per week
      to a dose of 66-68 Gy in 9.5 or 6.5 weeks, respectively. RESULTS: Overall, split
      course and continuous treatment resulted in a 5-year loco-regional control of 30%
      and 41% (P = 0.007), respectively. However, the detrimental effects of split
      course were only found in moderately and well-differentiated tumors, where the 5
      year tumor controls were 38% and 21% after continuous and split-course treatment,
      respectively (P = 0.001). In contrast, in poorly differentiated tumors loco
      regional control was obtained in 44% of the cases for continuous and 40% for
      split-course treatment (P = 0.63). CONCLUSIONS: It is suggested that the ability
      to accelerate repopulation may be lost by dedifferentiation, and that
      prolongation of the overall treatment time only lead to reduced loco-regional
      control in well to moderately differentiated tumors.

PMID- 9165137
TI  - Carcinoma of the nasopharynx treated by radiotherapy alone: determinants of
      distant metastasis and survival.
AB  - PURPOSE: This retrospective study was conducted to identify the prognostic
      factors for distant metastasis and survival in a population of 378 patients with
      nasopharyngeal carcinomas treated by radiation therapy alone. MATERIALS AND
      METHODS: All patients were treated at the University of Texas M.D. Anderson
      Cancer Center between 1954 and 1992, following a consistent dose and volume
      prescription policy. There were 286 males and 92 females. The median age was 52
      years (range: 16-86 years). The majority of the patients were white Caucasians
      (282 patients,75%). Tumors were classified as squamous cell carcinomas (193;
      51%), lymphoepitheliomas (154; 41%), or unclassified carcinomas (31, 8%). Three
      fourths of the patients presented with AJCC Stage IV disease (T4, N0-3, 118
      patients; T1-3, N2-3 164 patients). The treatment techniques included opposed
      lateral fields with or without an anteroposterior or an anterior oblique pairs
      for dose supplementation to the primary site. Average total doses per T-stage
      ranged between 60.2 and 72.0 Gy. Median follow-up time was 10 years (range 0.3 to
      28.6 years). RESULTS: A total of 103 patients (27%) developed distant metastases
      at a median time of 8 months (range: 1-90 months). Actuarial rates for distant
      metastasis were 30%, 32%, 32% at 5, 10, and 20 years, respectively. Actuarial
      rates for disease specific survival at the same time points were 53%, 45%, and
      39% with 184 patients (49%) dying of their nasopharyngeal cancer. Advanced T
      stage, N-stage, and non-lymphoepithelioma histology were independent adverse
      prognostic factors for disease specific survival. Advanced N-stage and low neck
      disease were independent adverse prognostic factors for distant metastasis with a
      very high rate of distant metastases for those patients who presented with both
      adverse factors (relative risk 7.86). On average, patients with distant
      metastasis lived 5 months after they were diagnosed with metastatic disease
      (range: 0-172 months), although four patients (4%) survived more than 5 years
      after diagnosis. CONCLUSIONS: This study demonstrates good long term survival
      rates after definitive radiotherapy for patients with nasopharyngeal carcinomas.
      Patients with advanced and lower neck disease have the highest risk of developing
      distant failures. Such patients can be considered the reference risk group to
      test the value of adjunctive chemotherapy.

PMID- 9165138
TI  - Effect of arytenoid sparing during radiation therapy of early stage glottic
      carcinoma.
AB  - PURPOSE: To retrospectively evaluate the effect of arytenoid shielding on local
      control and complications in the treatment of early stage glottic carcinomas.
      MATERIALS AND METHODS: The analysis concerns 71 patients treated with megavoltage
      photons for stages Tis, T1 and T2 glottic carcinomas. In 31 patients the entire
      larynx was treated at 2 Gy/day to full dose (group 1, mean field area 41.5 cm2)
      and in 40 patients a posterior block was placed after a median dose of 54 Gy to
      protect the arytenoid cartilage (group 2, mean field area 38 cm2). The decision
      to shield 10-15 mm of the posterior aspect of the treatment volume was based on
      the presence or absence of involvement of the posterior third of the vocal cords.
      Median total dose was 70 Gy in both groups. RESULTS: RTOG grade 2 and 3 acute
      laryngeal complications were observed in 77% and 62.5% of patients in groups 1
      and 2, respectively (P = 0.25). The rate of grade 2-3 late laryngeal
      complications (mostly arytenoid edema) was similar in the two groups (13.6% vs
      20%, P = 0.83). Actuarial local control at 5 years was also similar in the two
      groups (T1: 85% vs 96.6%, P = 0.13 and T2: 82% vs 87.5%, P = 0.86). CONCLUSION:
      No objective differences could be shown in terms of acute or late laryngeal
      complications or in terms of local control related to the use of arytenoid
      shielding. As severe complications are rare and local control is very
      satisfactory using standard techniques, it is difficult to attribute any
      advantage to the use of arytenoid blocking.

PMID- 9165139
TI  - Administration of nicotinamide during a five- to seven-week course of
      radiotherapy: pharmacokinetics, tolerance, and compliance.
AB  - BACKGROUND AND PURPOSE: Nicotinamide was administered daily as a liquid
      formulation to head and neck cancer patients receiving a 5- to 7-week course of
      radiotherapy. The pharmacokinetics, compliance, and tolerance of this drug
      formulation were studied. MATERIALS AND METHODS: Blood samples were drawn and
      nicotinamide levels determined in 40 head and neck cancer patients. On the first
      treatment day serial samples were obtained followed by daily samples at the time
      of irradiation during the first and last full weeks of the treatment. Side
      effects of nicotinamide were monitored. RESULTS: In all patients peak
      concentrations greater than 700 nmol/ml could be obtained 0.25-3 h (mean 0.83 +/-
      0.73 h) after drug intake. During the first week of treatment plasma levels at
      the time of irradiation were adequate in 82% of the samples. This decreased to
      59% in the last week of treatment which can be partly attributed to reduced
      compliance. The most important side-effect of nicotinamide was nausea with or
      without vomiting occurring in 65% of the patients. Severe side-effects were
      associated with high plasma concentrations over subsequent days. Tolerance
      improved after a 25% reduction of dose in six of seven patients but plasma levels
      at the time of irradiation fell below 700 nmol/ml in four out of six of these
      patients. CONCLUSIONS: Peak plasma concentrations above the 700 nmol/ml level
      were obtained in all patients but these concentrations could not be reproduced
      during the entire course of the treatment in a significant portion of the
      subjects. Side-effects of nicotinamide are associated with plasma concentrations
      and tolerance can be improved by a moderate reduction of dose.

PMID- 9165140
TI  - Effect of megestrol acetate and prepulsid on nutritional improvement in patients
      with head and neck cancers undergoing radiotherapy.
AB  - BACKGROUND AND PURPOSE: Anorexia is a common problem in cancer patients who
      receive radiotherapy. In this current study, we attempt to determine the effect
      of megestrol acetate and prepulsid on appetite and nutritional improvement in
      patients with head and neck cancers undergoing radiotherapy. MATERIALS AND
      METHODS: One hundred twenty-nine consecutive patients with head and neck cancers
      treated between July 1993 and June 1994 were prospectively randomized to receive
      either megestrol acetate, 40 mg qid (megace group), prepulsid, 5 mg tid
      (cisapride group), or a placebo treatment (control group) during radiotherapy.
      Before radiotherapy, body weight (kg), appetite score, performance status,
      biochemical parameters and hematological parameters were evaluated, and the above
      noted clinical and biochemical parameters were assessed and recorded every other
      week. All patients received 6- 10 MV X-rays or Co-60 gamma-ray to head and neck
      region for a full course of radiotherapy, 61.2-75.6 Gy/7-9 weeks. RESULTS: Forty
      eight patients were enrolled in the megace group, 41 patients in the cisapride
      group, and 40 patients in the control group. At the 2nd, 4th, 6th and 8th week,
      as the radiation dose escalated, the megace group had significantly less body
      weight loss than did the cisapride and control groups (P = 0.045, 0.024, 0.006,
      0.003, respectively). The appetite scores of the megace group were significantly
      higher than those of the cisapride and control groups (P = 0.0001). However,
      there were no statistically significant differences in the change of albumin
      level among these three groups at the 2nd, 4th, 6th and 8th week (P > 0.05,
      respectively). CONCLUSIONS: Megestrol acetate can significantly decrease the
      degree of body weight loss, and can prevent the deterioration of appetite in
      patients with head and neck cancers receiving radiotherapy. However, prepulsid
      lacks the above-mentioned clinical benefits.

PMID- 9165141
TI  - Treatment portals for elective radiotherapy of the neck: an inventory in The
      Netherlands.
AB  - PURPOSE: To assess the variation in and the three-dimensional dosimetric
      consequences of treatment portals for elective neck irradiation. MATERIALS AND
      METHODS: Radiation oncologists (n = 16) from all major Head and Neck Co-operative
      Groups in The Netherlands (n = 11) were asked to delineate treatment portals on a
      lateral and an anterior simulation film in case of elective neck irradiation for
      a T3N0 tumour of the supraglottic larynx and a T2N0 tumour of the mobile tongue.
      In addition, they had to define their target, i.e. which parts of the neck nodal
      regions they would choose to irradiate electively for these particular tumour
      sites. Subsequently, treatment portals were compared and evaluated using CT-data
      and a 3-dimensional (3D) treatment planning system. RESULTS: Significant
      variations were found in the shapes and sizes of the applied treatment techniques
      and portals. Also, among radiation oncologists who elected to irradiate the same
      lymph node regions, a significant variation in the delineated treatment portals
      was observed. As a consequence, substantial variations in treated volumes and in
      calculated normal tissue complication probabilities (NTCPs) for the parotid- and
      submandibular glands were observed. CONCLUSION: For the tumour sites studied
      there appears to be a lack of standardisation in the areas of the neck to be
      irradiated electively. The observed differences may have consequences for the
      ultimate failure rate and particularly with regard to the side effects, e.g. the
      degree of xerostomia. It is argued that in the near future a more precise three
      dimensional definition on CT of the lymph node regions in the neck might allow
      for a better standardisation of the treatment portals and, in addition, for the
      development and application of conformal radiotherapy techniques for optimal
      sparing of the critical normal tissues (e.g. parotid- and submandibular glands)
      with maximum tumour control probability.

PMID- 9165142
TI  - Fractionated stereotactic radiotherapy for choroidal melanoma.
AB  - Stereotactic radiotherapy used for the treatment of choroidal melanoma made use
      of a 6-MeV linac with built-in multileaf collimators and a simple plastic head
      mold. The latter provided excellent head and ocular immobilization. The system
      resulted in highly localized dose distributions with a maximum 2-mm targeting
      error during fractionated treatments. Based on these techniques, sixteen patients
      with choroidal melanoma have so far been treated. Majority of patients received a
      total dose of 48 Gy in 8 fractions. Fourteen patients who presented with small-
      to moderate-sized tumors have remained free of relapse or major complications
      during the follow-up period of 3-42 months. Two patients who presented with an
      extensive tumor eventually required enucleation after irradiation. Technical
      precision required for stereotactic radiotherapy and reproducibility for
      fractionation appear adequate. Encouraging preliminary results justify further
      studies to evaluate its efficacy as an alternative to other conventional
      therapeutic approaches.

PMID- 9165144
TI  - The European core curriculum for radiotherapy technologists.
AB  - BACKGROUND: The Radiotherapy Technologist is the third member of the team
      responsible for the accurate delivery of radiotherapy to the cancer patient.
      Educational standards have been established for both radiotherapists and medical
      physicists and our group recognised the need to also standardise the education of
      radiotherapy technologists. MATERIALS AND METHODS: The project commenced in 1990
      and was completed by 1994 when an agreed core curriculum was presented at a
      consensus conference. All aspects of curriculum development and education
      delivery were reviewed during this four year period. RESULTS: Core topics were
      identified. educational entry standards described and a duration of three years,
      consistent with European Union mobility regulations, agreed. CONCLUSIONS: The
      core curriculum describes the standard necessary to be achieved for entry into
      the profession to ensure the optimum treatment is offered to all patients
      throughout the European Union. Regular review of the core curriculum should be
      carried out to ensure the defined standards are maintained.

PMID- 9165143
TI  - Impact of the interfraction interval on clonogenic cell survival in split-dose
      irradiation of R1H rhabdomyosarcoma of the rat in vitro.
AB  - PURPOSE: In a previous study, the response of the R1H rhabdomyosarcoma of the rat
      to conventional irradiation (1.83-2.75 Gy fractions once-daily) and
      hyperfractionated radiotherapy (0.92-1.38 Gy fractions with different time
      intervals between the two daily fractions) was investigated [Kleineidam, M.,
      Pieconka, A., Beck-Bornholdt, H.-P. Radiotherapy of the rhabdomyosarcoma R1H of
      the rat: influence of the time interval between two daily fractions during
      hyperfractionated radiotherapy. Radiother. Oncol. 30: 128-132, 1994]. Compared to
      once-daily irradiation, interfraction intervals of 2 h led to reduced tumour
      response, due to recovery from sublethal damage, and intervals of 5-6 h resulted
      in increased tumour response, possibly due to cell cycle effects. The purpose of
      the present study was to complement these tumour data by measuring clonogenic
      cell survival of R1H cells in vitro after split-dose irradiation. METHODS AND
      MATERIALS: Experiments were performed with 2 x 2.5 Gy and 2 x 3.5 Gy either at 21
      degrees C (preventing cell cycle progression) or at 37 degrees C (allowing for
      cell cycle effects). RESULTS: For 3.5 Gy fractions, a cell survival curve
      equivalent to the in vivo results was obtained with the lowest surviving fraction
      observed at time intervals of 6-7 h, but only when cells were incubated at 37
      degrees C during the interval. This phenomenon was absent in the 21 degrees C
      experiments. CONCLUSIONS: Our data provide further evidence to support the
      hypothesis that cell cycle effects are responsible for such observations. We
      conclude that the length of the interfraction interval has a considerable
      potential effect on tumour response to altered fractionation regimens.

PMID- 9165145
TI  - Patient information about radiation therapy: a survey in Europe.
AB  - BACKGROUND AND PURPOSE: We performed a survey to evaluate the present status and
      means of information given to patients treated by radiotherapy. A short
      questionnaire was sent, with the help of ESTRO, to 746 European heads of
      department with a request to send specific documents used for informing the
      patient. Within 2 months (March and April 1996) we received 290 answers (39%) and
      97 centres sent documents. MATERIALS AND METHODS: Analysis of the questionnaire
      and the documents was performed quantitatively with usual statistical methods and
      qualitatively with a socio-anthropological method of content analysis. RESULTS:
      Analysis of the questionnaire shows the major role of the radiation oncologist in
      giving information and writing documents. The 298 different samples sent from 97
      centres represent a wide panel with a booklet of general information (59
      booklets/57 centres), practical advice and specific explanations (177
      documents/49 centres) and informed consent (36 documents/28 centres). The
      anthropological study was centred on the way information was given, evaluation of
      the patient's understanding and analysis of documents sent. CONCLUSION: This
      preliminary survey needs to be completed by a study, including the patient's
      point of view and needs, about the information given.

PMID- 9165146
TI  - Tolerance to nicotinamide and carbogen with radiation therapy for glioblastoma.

PMID- 9165147
TI  - Low-dose radiotherapy for stage I seminoma: early results.

PMID- 9165148
TI  - Relation of contractile reserve during low-dose dobutamine echocardiography and
      angiographic extent and severity of coronary artery disease in the presence of
      left ventricular dysfunction.
AB  - Contractile reserve, during low-dose dobutamine echocardiography, is frequently
      used for the assessment of myocardial viability in patients with coronary artery
      disease (CAD) and left ventricular (LV) dysfunction. Whether contractile reserve
      is affected by the severity of the underlying CAD is presently unknown.
      Accordingly, we studied 58 patients with stable CAD and LV dysfunction who
      underwent coronary angiography and low-dose dobutamine echocardiography. In each
      vascular region the worst stenosis was identified and quantitated as percent
      diameter stenosis. Segmental wall motion during echocardiography was scored
      visually and rest and dobutamine wall motion score indexes were calculated.
      Contractile reserve was defined as > or = 1 grade improvement in wall motion
      score of > or = 2 contiguous segments along with > or = 20% reduction in global
      wall motion score index with dobutamine. There was no difference between patients
      with (n = 26) and without (n = 32) contractile reserve in percent coronary
      stenosis (89 +/- 17% vs 87 +/- 17%, p = 0.6), number of coronary arteries with >
      50% diameter stenosis (2.0 +/- 0.8 vs 2.2 +/- 0.7, p = 0.4), number of occluded
      coronary arteries (1.2 +/- 0.9 vs 1.1 +/- 0.9, p = 0.6), or the prevalence of
      collaterals demonstrated angiographically (61% vs 56%, p = 0.5). Our data
      demonstrates that in patients with CAD and LV dysfunction, the prevalence of
      contractile reserve during low-dose dobutamine echocardiography is independent of
      the angiographic extent and severity of CAD.

PMID- 9165149
TI  - Results of coronary stenting for unstable versus stable angina pectoris.
AB  - Coronary artery stenting has been shown to improve the short- and long-term
      results of coronary angioplasty in mainly stable patients with 1-vessel disease,
      but it is uncertain whether its use in an unstable clinical setting may be safe
      and useful. To evaluate the stenting efficacy in patients with unstable angina,
      we retrospectively examined our experience with the Palmaz-Schatz balloon
      expandable stent in 231 consecutive patients. Patients were divided into 2 groups
      on the basis of symptoms at the time of stent implantation: group U (132
      patients) had unstable angina, and group S (99 patients) had stable angina. After
      stent insertion, patients were treated with anticoagulant or combined
      antiplatelet therapy. Baseline characteristics of the 2 groups were comparable
      with the exception of age (higher in the unstable group) and angiographic
      characteristics of the target lesions (more unfavorable in unstable patients). In
      both groups, coronary stenting presented a high procedural success rate. Major in
      hospital complications occurred in 9 unstable (6.8%) and in 2 stable (2%)
      patients (p = NS) and were mainly related to subacute stent thrombosis. In both
      groups, subacute stent thrombosis mostly occurred in patients treated with
      anticoagulant therapy (7 of 9 unstable patients, 2 of 2 stable patients). At 6
      month follow-up, unstable and stable patients had a similar incidence of death
      (0%), Q-wave myocardial infarction (0%), and need of coronary artery bypass graft
      (3.2% vs 4%, p = NS), but coronary angioplasty repetition (4.8% vs 14%, p =
      0.027) and target vessel revascularization (6.3% vs 17%, p = 0.019) rates were
      lower in the unstable group. In conclusion, stent insertion increases the short-
      and midterm coronary angioplasty effectiveness in unstable angina, making it
      possible to achieve outcomes quite comparable to stable angina. Compared with
      conventional anticoagulant regimen, combined antiplatelet therapy after placement
      of coronary stents seems to reduce the incidence of subacute thrombosis also in
      this clinical setting.

PMID- 9165150
TI  - Usefulness of hemodynamic changes during adenosine infusion in predicting the
      diagnostic accuracy of adenosine technetium-99m sestamibi single-photon emission
      computed tomography (SPECT).
AB  - Whether adenosine myocardial perfusion single-photon emission computed tomography
      (SPECT) remains accurate for detecting coronary artery disease (CAD) in the
      absence of peripheral hemodynamic changes is unknown. To assess the hemodynamic
      correlates of perfusion defects, we studied 222 consecutive patients (age 71 +/-
      11 years) without prior myocardial infarction or revascularization who underwent
      adenosine technetium (Tc)-99m sestamibi myocardial perfusion SPECT and cardiac
      catheterization within 6 months of adenosine study. The SPECT protocol used
      separate acquisition of rest thallium-201 and adenosine Tc-99m sestamibi, which
      was semiquantitatively analyzed in 20 segments with a visual 5-point scoring
      system (0 = normal, 4 = absent uptake). The overall sensitivity, specificity, and
      predictive accuracy of adenosine Tc-99m sestamibi SPECT for detecting significant
      CAD were 93% (159 of 171), 73% (37 of 51), and 88% (196 of 222), respectively.
      The study population was grouped into 6 categories as a function of peripheral
      hemodynamic changes: (1) increase in heart rate by < or = 10 beats/min (n = 135);
      (2) increase in heart rate by > 10 beats/min (n = 87); (3) decrease in systolic
      blood pressure by < or = 10 mm Hg (n = 108); (4) decrease in systolic blood
      pressure by > 10 mm Hg (n = 114); (5) increase in heart rate by < or = 10
      beats/min and decrease in systolic blood pressure by < or = 10 mm Hg (n = 72);
      and (6) increase in heart rate by > 10 beats/min or decrease in systolic blood
      pressure by > 10 mm Hg (n = 150). The sensitivity, specificity, and predictive
      accuracy of adenosine sestamibi SPECT were similar in all 6 categories. The
      prevalence of left main or multivessel CAD and extent of scan abnormality were
      also similar among all groups. Thus, the diagnostic accuracy of adenosine Tc-99m
      sestamibi SPECT is high in patients with or without peripheral hemodynamic
      evidence of adenosine effect.

PMID- 9165151
TI  - Usefulness of ST-segment depression in non-infarct-related electrocardiographic
      leads in predicting prognosis after thrombolytic therapy for acute myocardial
      infarction.
AB  - This study investigated both the in-hospital and long-term prognostic
      significance of ST-segment depression in non-infarct-related leads in patients
      who received thrombolytic therapy after acute myocardial infarction (AMI). We
      evaluated 221 consecutive patients who were admitted with their first AMI and
      underwent thrombolysis. Patients were followed for an average of 31 months and
      were classified into 3 groups: group 1 included 51 patients with persistent ST
      segment depression, group 2 had 97 patients with transient ST-segment depression,
      and group 3 consisted of 73 patients without ST-segment depression (absent).
      Group 1 had significantly worse long-term survival during follow up by Kaplan
      Meier analysis (55%) versus group 2 (81%) and group 3 (94%) (p = 0.0004) and
      higher event rates. This prognostic significance seemed to be maintained in both
      the anterior and inferior wall AMI groups. Multivariate analysis, using the Cox
      model, showed that Killip class, in-hospital left ventricular ejection fraction,
      and the persistence of ST-segment depression on the predischarge
      electrocardiogram (group 1) were independent predictors of survival. ST-segment
      depression in non-infarct-related leads on the predischarge electrocardiogram is
      an independent risk factor for worse long-term survival after anterior as well as
      inferior AMI treated with thrombolytic therapy.

PMID- 9165152
TI  - Comparison of myocardial contrast echocardiography and coronary angiography for
      assessing the acute protective effects of collateral recruitment during occlusion
      of the left anterior descending coronary artery at the time of elective
      angioplasty.
AB  - To assess the immediate change in collateral flow distribution within the
      occluded myocardium and the acute protective effects on myocardial ischemia after
      coronary occlusion, myocardial contrast echocardiography (MCE) was performed in
      15 patients with normal left ventricular function undergoing elective coronary
      angioplasty of the left anterior descending artery, and the results were compared
      with those obtained from coronary angiography (CA). The sonicated or nonsonicated
      contrast material was injected into the right coronary artery before and during
      coronary occlusion and collaterals were graded on a 4-point scale (none = 0 to
      good = 3). Development of subjective anginal symptoms, ST-segment shift and wall
      motion abnormality during coronary occlusion were graded on a 4-point scale (none
      = 0 to severe = 3). Both MCE and CA detected a significant development in
      collateral flow during coronary occlusion. There was no significant correlation
      between MCE and CA collateral grades before or during coronary occlusion. The
      collateral flow assessed with MCE was inversely but significantly correlated with
      development of subjective anginal symptoms (r(s) = -0.70, p <0.01), ST-segment
      shift (r(s) = -0.78, p < 0.005) or wall motion abnormality (r(s) = -0.91, p <
      0.001) during coronary occlusion. In contrast, the angiographic collateral flow
      was not correlated with development of anginal symptoms (r(s) = -0.46, p = 0.10),
      ST-segment shift (r(s) = -0.41, p = 0.14), or wall motion abnormality (r(s) = 
      0.26, p = 0.35). The present study suggested that the acute protective effects of
      coronary collaterals during coronary occlusion were closely associated with
      myocardial perfusion rather than the angiographic epicardial collateral vessel
      filling, and thus MCE was useful in assessing the acute protective effects of
      coronary collaterals during coronary occlusion.

PMID- 9165153
TI  - Comparison of balloon angioplasty versus debulking devices versus stenting in
      right coronary ostial lesions.
AB  - Angioplasty of aorto-ostial stenosis is associated with lower procedural success
      and a higher complication rate. The aim of the present study was to compare the
      acute and long-term results of balloon and new device angioplasty in 110
      consecutive patients with right coronary ostial lesions. Patients were divided
      into 3 groups according to the angioplasty device used: group I (balloon only, n
      = 26), group II (debulking devices including excimer laser, directional and
      rotational atherectomy, n = 26), group III (stent, n = 58). Procedural success
      was highest in group III (96%) followed by group I (88%), and group II (77%). In
      hospital complications were similar among the groups (p = NS). Patients in group
      III achieved the highest acute gain (2.61 mm) followed by groups II (1.92 mm),
      and I (1.39 mm, p <0.05). During follow up, target lesion revascularization
      and/or bypass surgery was required in 24% of patients in group III compared with
      47% and 40% in groups I and II, respectively (p <0.05). Cardiac-event free
      survival was highest in the stent group (74%, p <0.005) and was similar between
      the balloon (39%) and debulking device groups (45%). Thus, among the currently
      available technologies, stenting of right coronary ostial lesions appears to
      provide excellent angiographic and long-term results.

PMID- 9165154
TI  - Effect of coronary angioplasty on precordial QT dispersion.
AB  - Dispersion of the QT interval is a measure of inhomogeneity of ventricular
      repolarization. Because ischemia is associated with regional abnormalities of
      conduction and repolarization, we hypothesized that the surface
      electrocardiographic interval dispersion would increase in patients with
      symptomatic coronary artery disease in the absence of myocardial infarction and
      that successful revascularization would reduce QT interval dispersion. Thirty
      seven consecutive patients with ischemia due to 1-vessel coronary artery disease
      without prior myocardial infarction who underwent percutaneous transluminal
      coronary angioplasty (PTCA) were evaluated. Standard 12-lead electrocardiograms
      were performed 24 hours before, 24 hours after, and late (>2 months) after PTCA.
      Precordial QT interval dispersions were determined from differences in the
      maximum and minimum corrected QT intervals. Mean QT interval dispersion before
      PTCA was 60 +/- 9 ms, immediately after PTCA 23 +/- 14 ms (p <0.001), and late
      after PTCA 29 +/- 18 ms (p <0.001 vs before PTCA). The shortest precordial QT
      interval increased immediately after PTCA (367 +/- 40 vs 391 +/- 39 ms; p <0.02)
      and then remained stable late after PTCA (376 +/- 36 ms, p = NS vs immediately
      after PTCA). Symptomatic recurrent ischemia in 8 patients with documented
      restenosis increased QT interval dispersion (56 +/- 15 ms [p <0.01] vs 25 +/- 14
      ms immediately after PTCA), which decreased again after successful repeat PTCA
      (22 +/- 13 ms [p <0.01] vs before the second PTCA). QT interval dispersion
      decreases after successful coronary artery revascularization and increases with
      restenosis. Therefore, QT interval dispersion may be a marker of recurrent
      ischemia due to restenosis after PTCA.

PMID- 9165155
TI  - Angioscopy variables predictive of early angiographic outcome after excimer laser
      assisted coronary angioplasty.
AB  - This study attempted to determine whether anatomic findings at angioscopy were
      associated with adverse early angiographic outcomes following excimer laser
      assisted coronary angioplasty. Predictive factors of either coronary abrupt
      vessel closure or early (< or =24 hours) restenosis after percutaneous coronary
      angioplasty, including clinical and angiographic variables, have been widely
      evaluated. The role of angioscopic findings may contribute to identification of
      patients at risk for early poor outcome. Thirty-seven patients with severe
      lesions, including 23 total occlusions which underwent successful percutaneous
      transluminal coronary angioplasty (PTCA) with laser irradiation and adjunctive
      balloon dilatation (n = 35), or stand alone laser (n = 2), had concomitant
      angioscopic imaging of the target vessel. All patients had a 24-hour angiographic
      follow up. Early unfavorable outcome (n = 15) was defined as abrupt vessel
      closure or restenosis (> or = 50% stenosis) at 24 hours. By multivariate logistic
      regression analysis, immediate post-PTCA residual percent stenosis was associated
      with a poor outcome (restenosis: 33 +/- 22% vs no restenosis: 21 +/- 14%, p =
      0.05). Angioscopic red thrombus aspect was the most significant correlate for
      early closure or restenosis (7 of 15 patients with unfavorable outcome vs 2 of 22
      patients with favorable outcome, odds ratio, 22.9; p < 0.01) and was associated
      with a significantly higher early minimal lumen diameter loss (1 +/- 0.8 mm in
      the presence of a red thrombus vs 0.3 +/- 0.5 mm without thrombus, p < 0.005).
      Red thrombus appearance is associated with an unfavorable early angiographic
      outcome in patients who undergo laser-assisted coronary angioplasty.

PMID- 9165156
TI  - Usefulness of hypertriglyceridemia in predicting myocardial infarction late after
      coronary artery bypass operation.
AB  - We prospectively followed 446 consecutive patients who had coronary bypass
      operations 15 years earlier. Serum levels of cholesterol and triglycerides were
      measured before and 5 years after bypass, and we established the relation between
      these lipid levels and the incidence of myocardial infarction (MI) and cardiac
      mortality during 15 years of follow-up. Follow-up was complete in 99.8% of the
      patients and averaged 15.4 years for the survivors. Multivariate Cox proportional
      hazards analysis revealed that patients with preoperative hypertriglyceridemia (>
      or = 2.0 mmol/L [176 mg/dl]) had a 2.1 times increased risk for MI during follow
      up (p = 0.04). Hypertriglyceridemic patients 5 years after surgery had a 2.2
      times increased risk for MI during the subsequent follow-up period, although this
      difference was not statistically significant (p = 0.09). The only significant
      risk factor for MI 5 years after surgery was smoking. Hypercholesterolemia (> or
      = 6.5 mmol/L [254 mg/dl]) both before and 5 years after surgery was not a risk
      factor for MI during follow-up. Cardiac mortality was not significantly related
      to either hypercholesterolemia or hypertriglyceridemia. Independent predictors
      for cardiac mortality were poor left ventricular function, diabetes mellitus,
      incomplete revascularization, and the use of sequential bypass grafts. These data
      provide evidence that hypertriglyceridemia, both before and 5 years after
      surgery, have predictive value for the incidence of MI during long-term follow-up
      after venous coronary bypass surgery.

PMID- 9165157
TI  - Transesophageal echocardiographic predictors for maintenance of sinus rhythm
      after electrical cardioversion of atrial fibrillation.
AB  - The aim of this study was to assess the value of transesophageal echocardiography
      (TEE) in patients with atrial fibrillation in predicting restoration and
      maintenance of sinus rhythm after electrical cardioversion. TEE was performed in
      62 patients with atrial fibrillation before their first elective cardioversion.
      Clinical variables evaluated were: age, gender, duration, and etiology of atrial
      fibrillation. TEE variables included: left atrial (LA) length, width, and size,
      LA annulus size, as well as presence of LA spontaneous contrast, thrombus and
      mitral regurgitation, LA appendage size and flow, and left ventricular function.
      Based on initial outcome of cardioversion, patients were grouped into patients
      who remained in atrial fibrillation and in whom sinus rhythm was restored. The
      latter group of patients was followed for 1 year, and grouped into patients who
      reverted to atrial fibrillation and in whom sinus rhythm was maintained.
      Successful cardioversion was achieved in 50 of 62 patients (81%). None of the
      clinical or TEE variables were related to initial outcome. At 1-year follow-up,
      29 of 50 patients (58%) who underwent successful cardioversion continued to have
      sinus rhythm. The following variables were related to maintenance of sinus
      rhythm: duration of atrial fibrillation (6.7 +/- 7.3 vs 2.0 +/- 2.4 months; p <
      0.005); LA length (6.2 +/- 0.7 vs. 5.5 +/- 1.0 cm; p < 0.008); width (5.1 +/- 0.5
      vs. 4.5 +/- 0.7 cm; p < 0.002); size (26.4 +/- 5.0 vs 19.8 +/- 6.5 cm2; p <
      0.0005); annulus size (4.0 +/- 0.2 vs 3.7 +/- 0.3 cm; p < 0.0005); presence of LA
      spontaneous contrast (13 [62%] vs 4 [14%]; p < 0.002), and LA appendage flow (19
      +/- 8 vs 36 +/- 15 cm/s; p < 0.0005). In multivariate logistic regression
      analysis, LA annulus size, but especially LA appendage flow, were significantly
      associated with maintenance of sinus rhythm. Thus, in TEE-guided electrical
      cardioversion of atrial fibrillation, variables often used to assess
      thromboembolic risk may also be used to predict 1-year outcome of cardioversion.

PMID- 9165158
TI  - Feasibility and sensing thresholds of temporary single-lead VDD pacing in
      intensive care.
AB  - Long-term pacemaker treatment of patients with a high-degree atrioventricular
      (AV) block routinely uses AV synchronous pacing because of its hemodynamic
      advantages compared with VVI pacing. In cases of temporary pacing, however, the
      limitations inherent in attempting to reliably position a temporary atrial lead
      generally influences the use of VVI pacing. We therefore tested the use of
      temporary single-lead VDD pacing, making AV pacing possible with only 1 lead, in
      22 patients requiring temporary pacing due to a high-degree AV block. AV
      synchronous stimulation was achieved in all patients using a quadripolar lead
      with an atrial dipole with the atrial rings spaced 30 mm apart. During follow-up
      (14.1 +/- 12.5 hours) intermittent undersensing was detected in 4 of the 22
      patients. We initially evaluated the atrial sensing threshold by decreasing the
      pacemaker device sensitivity stepwise in all patients (1.54 +/- 1.08 mV; n = 22).
      In 15 patients an intra-atrial electrocardiogram was recorded. During the
      breathing cycle, the maximum P-wave amplitude was significantly different from
      the minimum P-wave amplitude (2.19 +/- 1.00 mV vs 1.25 +/- 0.65 mV, p < 0.005).
      The atrial signal detected by the single lead was further analyzed in 10 of 15
      patients using various filters. A mean signal loss of 45% was observed,
      increasing the lower bandpass frequency from 0.1 to 40 Hz (1.73 +/- 0.71 mV vs
      0.92 +/- 0.51 mV, p < 0.02). Lowering the upper filter range from 1,000 Hz down
      to 100 Hz did not significantly influence the atrial signal (1.73 +/- 0.71 mV vs
      1.61 +/- 0.75 mV, NS). Single-lead VDD pacing, even on a temporary basis, is a
      reliable means of achieving AV synchronous pacing. Due to the floating atrial
      dipole, the system is characterized by a high degree of variability in the atrial
      signal with intermittent lower values. A significant signal loss must be expected
      when a lower bandpass frequency of 40 Hz is used.

PMID- 9165159
TI  - Relation of daily activity levels in patients with chronic heart failure to long
      term prognosis.
AB  - Symptom-limited, laboratory-based exercise tests are often used to define
      prognosis in patients with chronic heart failure, but they do not relate to
      measures of normal daily activity. Invasive measures of central hemodynamics
      similarly relate poorly to outcome. Pedometer scores of weekly walking are
      markedly reduced in patients with heart failure, but whether this less artificial
      measure of exercise capacity is important in predicting prognosis is not known.
      Eighty-four patients with chronic heart failure were followed for a mean of 710
      days during which 44 died and 3 underwent cardiac transplantation. Symptom
      limited treadmill exercise capacity using 2 different protocols did not predict
      survival, whereas reduced weekly pedometer scores were strong predictors of death
      (p < 0.001). Other variables that predicted death included resting cardiac
      output, arterial blood pressure, diuretic requirements, New York Heart
      Association class, increased bilirubin, and hyponatremia (all p < 0.01). Reduced
      levels of daily activity are strong predictors of death in chronic heart failure
      and appear more powerful than laboratory-based exercise tests. This type of
      assessment is valuable in identifying patients at high risk and provides an
      objective measure of incapacity during normal daily life. The exercise capacity
      of patients unable to exercise in the laboratory could also be assessed using
      this technique. This may prove invaluable in clinical and mortality trials.

PMID- 9165161
TI  - Familial incidence of late ventricular potentials and electrocardiographic
      abnormalities in arrhythmogenic right ventricular dysplasia.
AB  - Familial forms of arrhythmogenic right ventricular dysplasia (ARVD) have been
      described. Signal-averaged electrocardiograms (SAECGs) and standard
      electrocardiograms have been used to detect ARVD. The purpose of this prospective
      study, for a given family member, was to evaluate the risk of having ARVD or only
      belonging to an affected family. To address these issues, we assessed the
      incidence of late ventricular potentials and electrocardiographic (ECG)
      abnormalities in the families of our patients with ARVD. SAECGs and
      electrocardiograms were recorded in 101 eligible family members and compared with
      those recorded in ARVD patients with sustained ventricular tachycardia (13
      patients in 12 families), and in 37 control subjects with a normal
      electrocardiogram. The incidence of late ventricular potentials was significantly
      higher in family members than in control subjects (16% vs 3%, p <0.05). The
      incidence of ECG abnormalities was 34% in family members. When the incidence of
      late ventricular potentials and/or ECG abnormalities were added up, results were
      38% abnormal findings in family members. Late ventricular potentials and/or ECG
      abnormalities were found in members of all 7 families; these abnormalities were
      initially thought to be sporadic forms, and thereafter were classified as
      familial forms. Thus, SAECGs and standard ECG recordings in ARVD family members
      showed 38% abnormal findings, and that all cases of ARVD could be classified as
      familial forms. The incidence of familial forms of ARVD was greater than was
      previously believed, which is highly suggestive of a genetic transmission of the
      disease in our geographic area.

PMID- 9165160
TI  - Predictors of long-term event-free survival after percutaneous balloon mitral
      valvuloplasty.
AB  - Previous studies have shown that long-term event-free survival after percutaneous
      balloon mitral valvuloplasty (PBMV) could be predicted by several baseline
      characteristics. However, the extent of the predictive variables has not been
      defined accurately yet. In this study, 40 baseline demographic, clinical,
      echocardiographic, and hemodynamic variables of 128 consecutive patients with
      mitral stenosis who underwent PBMV in a single institution, were analyzed in
      order to predict long-term event-free survival, defined as absence of death,
      mitral valve replacement, or repeat PBMV. Univariate survival analysis showed
      that age (p = 0.03), history of commissurotomy or mitral valvuloplasty (p =
      0.05), calcium grade (p = 0.008), echo score (p = 0.0001), preprocedure cardiac
      output (p = 0.03), preprocedure valve area (p = 0.0007), postprocedure mean left
      atrial pressure (p = 0.0001), postprocedure valve area (p = 0.0001),
      postprocedure valve gradient (p = 0.013), and postprocedural mitral regurgitation
      (p = 0.01) were statistically significant predictors of event-free survival.
      Additionally, the absolute and/or relative procedural change of the following
      variables were found to be statistically significant predictors of event-free
      survival: left atrial pressure (p = 0.01), valve area (p = 0.0001), and valve
      gradient (p = 0.02). Multivariate Cox proportional hazard analysis indicated that
      when only variables available before the procedure were considered, echo score (p
      = 0.002) and preprocedure valve area (p = 0.0002) were found to be independent
      predictors of event-free survival. When both pre- and postprocedure variables
      were considered, echo score (p = 0.002) and postprocedure valve area (p = 0.0001)
      were found to be independent predictors of event-free survival. In conclusion,
      mitral valve morphology reflected by echo score, and baseline and postprocedure
      mitral valve area were found to be the strongest independent predictors of event
      free survival after PBMV.

PMID- 9165162
TI  - Dobutamine pharmacokinetics during dobutamine stress echocardiography.
AB  - Many patients fail to achieve target heart rate during dobutamine stress
      echocardiography (DSE). We evaluated the pharmacokinetics of dobutamine during
      DSE to determine whether patients with an impaired chronotropic response have
      higher rates of dobutamine clearance and consequently relatively lower plasma
      dobutamine levels. Plasma dobutamine levels, heart rate, and left ventricular
      (LV) ejection fraction (EF) were measured in 13 male patients referred for DSE at
      baseline and at the end of stepped 3-minute dobutamine infusions of 5, 10, 20,
      and 30 microg/kg/min. Dobutamine levels increased with doses: 27 +/- 10, 111 +/-
      17, 275 +/- 17, and 403 +/- 28 ng/ml (mean +/- SEM). There was no relation
      observed between the plasma dobutamine level achieved at the 30-microg infusion
      dose and the increase in heart rate from baseline (r = 0.066; p = 0.83). Baseline
      LVEF and a measure of chronotropic beta responsivity were identified as
      independent predictors of dobutamine clearance, together accounting for 73% of
      the variance in dobutamine clearance. In conclusion, (1) there is a dose
      dependent increase in plasma dobutamine levels during DSE, (2) dobutamine
      clearance is positively related to baseline LVEF and is partially mediated by a
      beta-receptor mechanism, and (3) an impaired chronotropic response during DSE is
      not due to failure to achieve a sufficiently high dobutamine level. We conclude
      that in patients who lack an adequate heart rate response during the early stages
      of DSE (e.g., up to 20 microg/kg/min infusion), administration of atropine rather
      than progressively higher amounts of dobutamine may provide a more effective
      strategy to achieve target heart rate.

PMID- 9165163
TI  - The clinical therapeutic implications of the Scandinavian Simvastatin Survival
      Study.
AB  - This analysis of the Scandinavian Simvastatin Survival Study (4S) describes how
      the design, implementation, and results answer most questions or concerns of
      practicing physicians regarding practicality and advantages of blood cholesterol
      lowering drug intervention in patients who already have coronary artery disease.
      The results demonstrated that a drug with the safety and efficacy profile of
      simvastatin, utilized as it would be in a physician's office, can improve
      mortality and morbidity in patients with existing coronary disease without
      important side effects, and reduce hospitalizations for patients with coronary
      heart disease.

PMID- 9165164
TI  - Changes in immediate outcome of percutaneous transluminal coronary angioplasty in
      multivessel coronary artery disease in 1990 to 1991 versus 1994 to 1995.
AB  - Coronary angioplasty has undergone major technical changes since the period of
      inclusion in the randomized trials, comparing it with surgery, particularly with
      the increased use of coronary stents. This study shows improved in-hospital
      outcome in terms of primary success and complication rates in patients treated
      with coronary angioplasty for multivessel disease from 1994 to 1995, compared
      with the 1990 to 1991 period.

PMID- 9165165
TI  - Usefulness of directional coronary atherectomy in patients with acute anterior
      myocardial infarction.
AB  - To assess the usefulness of directional coronary atherectomy (DCA) in acute
      myocardial infarction (AMI), 139 consecutive patients with anterior wall AMI
      undergoing successful catheter intervention were studied. The reocclusion rate
      was significantly lower in the last 70 patients who underwent DCA as aggressively
      as possible compared with the first 69 patients treated with coronary balloon
      angioplasty (12.1% vs 3.0%, p <0.05).

PMID- 9165166
TI  - Angioscopic characteristics of coronary narrowing in patients with recurrent
      myocardial ischemia after myocardial infarction.
AB  - Coronary angioscopy was used to elucidate the underlying substrate of the culprit
      lesion in 20 patients with postinfarction ischemia and in 19 patients with other
      types of unstable angina. Plaque characteristics were similar in both groups, but
      red thrombi and occlusive thrombi were more frequently seen in patients with
      postinfarction ischemia.

PMID- 9165167
TI  - Effects of components of meals (carbohydrate, fat, protein) in causing
      postprandial exertional angina pectoris.
AB  - We have shown that unlike fat, protein, xylose, or water, the carbohydrate
      component of the meal accelerates myocardial ischemia, reduces exercise capacity,
      and is associated with a more rapid increase in the determinants of myocardial
      oxygen consumption than exercise in the fasting state. Our results suggest a role
      for a larger increase in sympathetic nervous activity and/or release of
      vasoactive gastrointestinal peptides after carbohydrate, but not fat or protein,
      meals in postprandial angina.

PMID- 9165168
TI  - Effects of zatebradine (ULFS 49 CL), a sinus node inhibitor, on heart rate and
      exercise duration in chronic stable angina pectoris. Zatebradine Investigators.
AB  - Zatebridine selectively reduces resting and exercise heart rate without any other
      myocardial effects. In this study, despite significant reductions in resting and
      exercise heart rate, there were no clinically significant effects on myocardial
      ischemia, suggesting that the anti-ischemic effect of heart rate reduction should
      be reevaluated.

PMID- 9165169
TI  - Liver transplantation after coronary artery bypass grafting.
AB  - Twelve patients are described who had liver transplantation after coronary artery
      bypass grafting (CABG). The liver disease in most of the patients was a
      consequence of hepatitis C resulting from blood transfusions at the time of CABG.

PMID- 9165170
TI  - Effect of preexisting epicardial patch electrodes on defibrillation thresholds of
      unipolar defibrillators.
AB  - The question is addressed whether patients with thoracotomy defibrillators and
      failing epicardial electrodes can be effectively treated with the implantation of
      prepectoral unipolar ("active can") defibrillators. Results indicate that
      abandoned epicardial patches in the pathway of unipolar defibrillation currents
      do not affect defibrillation thresholds and active can efficacy.

PMID- 9165171
TI  - Incidence and implications of abrasion of implantable cardioverter-defibrillator
      leads.
AB  - Severe abrasion of implantable cardioverter-defibrillator leads is frequently
      found during abdominal generator replacement and occasionally results in lead
      system failure. Careful inspection of leads at the time of generator replacement
      will identify such abrasions, and, in some cases, lead repair or replacement may
      be indicated.

PMID- 9165172
TI  - QT dispersion is a marker for life-threatening ventricular arrhythmias after
      atrioventricular nodal ablation using radiofrequency energy.
AB  - QT dispersion has been cited as a measure of nonuniform myocardial repolarization
      and a predictor of sudden cardiac death. We describe 38 patients who underwent
      atrioventricular nodal ablation, 3 of whom had an increase in measured QT
      dispersion and experienced potentially fatal, pulseless, polymorphic ventricular
      tachycardia after the procedure.

PMID- 9165173
TI  - Reproducibility of the ST-segment depression/heart rate analysis of the exercise
      electrocardiographic test in asymptomatic middle-aged population.
AB  - The reproducibility of the ST-segment depression against heart rate (ST/HR)
      hysteresis, ST/HR index, and end-exercise ST depression between the repeated
      exercise electrocardiographic tests were determined in 61 asymptomatic middle
      aged subjects. The findings support the clinical utility of the ST/HR hysteresis,
      but it is noteworthy that the results also suggest that the magnitude of change
      in the exercise electrocardiographic variables, which has to be observed to make
      the clinician confident that a real diagnostic change has occurred, is
      surprisingly large.

PMID- 9165174
TI  - P-wave morphology during right atrial pacing before and after atrial flutter
      ablation--a new marker for success.
AB  - Fourteen patients with typical atrial flutter underwent pacing from the low
      lateral right atrium and the proximal coronary sinus in normal sinus rhythm
      before and after catheter ablation. During low lateral right atrial pacing, a
      positive change in P-wave morphology in the inferior leads was noted in every
      patient (n = 12) in whom bidirectional block was achieved; no recurrence was
      noted in any of these patients.

PMID- 9165175
TI  - Clinical usefulness of slow pathway ablation in patients with both paroxysmal
      atrioventricular nodal reentrant tachycardia and atrial fibrillation.
AB  - Some patients with atrioventricular (AV) node reentrant tachycardia (AVN RT) also
      presented with atrial fibrillation (AF). In this study we demonstrate that slow
      pathway ablation is able to suppress both AVN RT and AF in subjects without
      structural heart abnormalities, whereas in patients with structural heart
      abnormalities after ablation AF frequently recurs.

PMID- 9165176
TI  - Effects of aerobic training on exaggerated blood pressure response to exercise in
      African-Americans with severe systemic hypertension treated with indapamide +/-
      verapamil +/- enalapril.
AB  - Hypertensive patients are likely to have an exaggerated blood pressure (BP)
      response during physical exertion. When moderate aerobic exercise was added to
      medical antihypertensive therapy in patients with severe hypertension, excessive
      elevations in BP during physical exertion were attenuated even with a modest
      reduction in BP at rest.

PMID- 9165177
TI  - Elevated soluble CD14 receptors and altered cytokines in chronic heart failure.
AB  - We hypothesized that in patients with chronic heart failure mesenteric venous
      congestion leads to increased bowel permeability, bacterial translocation, and
      thereby endotoxin release; the increased endotoxin challenge then causes immune
      activation with increased soluble CD14 levels and tumor necrosis factor (TNF)
      alpha production. Patients with high soluble CD14 levels (indicative of endotoxin
      cell interaction) have markedly increased plasma levels of TNF-alpha, soluble TNF
      receptors 1 and 2, and intracellular adhesion molecule-1, supporting this
      hypothesis.

PMID- 9165178
TI  - Transcatheter occlusion of native persistent ductus arteriosus using conventional
      Gianturco coils.
AB  - Two hundred eleven patients with small- to moderate-sized native patent ductus
      arteriosus underwent closure using Gianturco coils, employing the transvenous
      multiple catheter approach. Short-term results showed a high rate of complete
      occlusion and a potential long-term complication of mild left pulmonary artery
      stenosis in a small number of patients.

PMID- 9165179
TI  - Association between plasma homocysteine and extracranial carotid arterial disease
      in older persons.
AB  - The data demonstrate that high plasma homocysteine levels and low plasma folate
      and vitamin B12 levels are associated with a higher prevalence of 40% to 100%
      extracranial carotid arterial disease (ECAD) in older men and women. Elevated
      plasma homocysteine levels were observed in 45% of the older men with 40% to 100%
      ECAD versus 20% of the older men with 0% to 39% ECAD, and in 40% of the older
      women with 40% to 100% ECAD versus 18% of the older women with 0% to 39% ECAD.

PMID- 9165180
TI  - Prevalence and prognostic significance of right-sided cardiac mobile thrombi in
      acute massive pulmonary embolism.
AB  - The prevalence of right-sided cardiac mobile thrombi, "in transit" from the
      systemic venous system, was 18% in a series of 130 patients with massive
      pulmonary embolism referred to early echocardiography and receiving thrombolytic
      drugs (56%) or intravenous heparin (40%). The mortality rate was lower than
      previously reported and seemed to be related more to clinical and hemodynamic
      impairment than to presence of thromboembolus.

PMID- 9165181
TI  - Effect of atenolol on birth weight.
AB  - To investigate the possible harmful effects of early antihypertensive drug
      therapy with atenolol versus other therapies on pregnancy outcome, we reviewed
      the records of 398 women referred to our antenatal hypertension clinic between
      1980 and 1995. Babies born to women taking atenolol were significantly lighter
      than babies born to women taking other beta blockers, other antihypertensive
      drugs, or no therapy, suggesting that atenolol might be detrimental in early
      pregnancy.

PMID- 9165182
TI  - Cardiac troponin T concentration after coronary balloon angioplasty.

PMID- 9165183
TI  - The importance of acute phase proteins in acute coronary syndromes.

PMID- 9165184
TI  - Decrease in and polarization of dental caries occurrence among child and youth
      populations, 1976-1993.
AB  - With data on children's dental state from 1976 to 1993, we evaluated how the size
      of the high-caries group has changed concurrently with simultaneously decreasing
      mean numbers of teeth with past or current caries. Information related to all
      dental check-ups done for 5- and 15-year-olds in Helsinki, some 4,000 subjects of
      each age by year, consisted of numbers of teeth with caries experience (dmft or
      DMFT) and of all decayed teeth (dt + DT). Polarization of dental caries was
      described as the proportion of high-caries groups in each year, both in terms of
      caries experience and current untreated caries, diagnosed at subjects' annual
      clinical dental check-ups. For 5-year-olds, the high-caries group by caries
      experience included patients with their dmft > or = 3. For 15-year-olds the
      limits were set at DMFT > or = 6 and DMFT > or = 15. The high-caries group in
      terms of untreated caries was similar for both age groups: dt + DT > or = 3.
      Furthermore, polarization of caries was calculated as the share of numbers of
      both dmf or DMF teeth and dt + DT in each high-caries group of the total number
      of such teeth in the entire age cohort. During the 17 years, mean dmft for 5-year
      olds decreased from 4.6 to 0.8 and mean dt + DT from 0.9 to 0.6. In 1993, 78% had
      their dmft = 0, whereas only 8% of the patients accounted for 76% of all decayed
      teeth. For 15-year-olds the decrease was even greater: their DMFT fell from 12.1
      to 3.0 and their dt + DT from 3.1 to 0.8. However, only 26% had their DMFT = 0 in
      1993, with 55% of all dt + DT occurring in 10% of the patients. The present
      results confirmed a strong polarization in caries for both age cohorts, showing
      the need for renewed strategies in preventive caries treatment.

PMID- 9165185
TI  - Rise and fall of caries prevalence in German towns with different F
      concentrations in drinking water.
AB  - The rise and fall of caries prevalence (DMFT) and its relation to changing F
      concentration of drinking water and other health-related factors is analysed
      based on dental findings of more than 286,000 subjects of either sex (6-15 years
      old) from the two industrial towns Chemnitz and Plauen. Water fluoridation (1.0
      +/- 0.1 ppm F) was implemented in Chemnitz (formerly Karl-Marx-Stadt) in 1959. It
      was in operation until autumn 1990 with an interruption lasting 22 months around
      the year 1971. In the F-poor town of comparison, Plauen, 55% of the citizens were
      supplied with F-enriched drinking water (0.9 ppm F) during the years 1972-1984.
      Another 20% received F-containing mixed water (0.4-0.7 ppm F). During the first
      three decades of the study the level of caries prevalence was strictly correlated
      with the availability of an optimal caries preventive F concentration in the
      drinking water. Water fluoridation was followed by a decrease of caries, and
      interruptions in fluoridation were followed by increasing caries levels. A
      different caries trend was observed in the years from 1987 to 1995. There was a
      significant caries decrease down to the lowest DMFT (2.0) since 1959 in spite of
      the fact that only F-poor water was available over years in both towns. This
      improvement of oral health is explained by changes in caries-preventive and
      environmental conditions.

PMID- 9165186
TI  - Randomized clinical trial of the effect of prenatal fluoride supplements in
      preventing dental caries.
AB  - This randomized, double-blind study tested the caries-preventive efficacy of
      prenatal fluoride supplementation in 798 children followed until age 5.
      Initially, 1,400 women in the first trimester of pregnancy residing in
      communities served by fluoride-deficient drinking water were randomly assigned to
      one of two groups. During the last 6 months of pregnancy the treatment group
      received 1 mg fluoride daily in the form of a tablet and the control group
      received a placebo. Both treatment and control subjects were encouraged to use
      postnatal dietary fluoride supplements. Caries was measured in children at age 3
      and 5 while fluorosis was assessed at age 5. Caries activity was very low in both
      study groups: 92% of children remained caries-free in the treatment group and 91%
      remained caries-free in the placebo group. Fluorosis was observed in 26 subjects,
      all classified as very mild. Overall, there were no statistically significant
      differences in the study groups with respect to caries and fluorosis in deciduous
      teeth. The study had sufficient power to detect an absolute risk reduction of
      5.1% while only a 1.5% reduction was observed. These findings do not support the
      hypothesis that prenatal fluoride has a strong caries-preventive effect.

PMID- 9165188
TI  - Fractal structure of caries.
AB  - Between 1991 and 1993, the data of 479 clinical records were compiled about
      caries in the permanent teeth of subjects of both sexes, whose dental
      examinations were carried out in a private dental clinic in the city of Salamanca
      and who were distributed by age into groups of 16-65, 26-55 and 36-45 years.
      Using the method known as system of expansion-contraction, we showed that caries
      has a non-linear dynamic, whose evolution in time is difficult to predict and
      which has a fractal geometry. This study shows the fractal geometry of caries and
      to achieve this uses a little-known method which will be of great use in future
      research.

PMID- 9165187
TI  - Oral health of 3-year-old children and their parents after 29 months of child
      focused antiatherosclerotic dietary intervention in a prospective randomized
      trial.
AB  - A long-term prospective, randomized dietary intervention to prevent exposure of
      children to the known atherosclerosis risk factors (the STRIP baby project) was
      started when the age of the children was 7 months. The aim of this substudy was
      to analyze the oral effects of the dietary intervention in the children and their
      parents when the children had reached the age of 3 years. Every fifth family of
      the main study was invited to this substudy (n = 179). Those studied (n = 148)
      represented well the intervention and the control groups and both genders in
      terms of intake of saturated fatty acids, the dietary polyunsaturated fatty acid
      to saturated fatty acid (PUFA/SAFA) ration and serum cholesterol and HDL
      cholesterol concentrations. Though no difference was found in sucrose consumption
      between the intervention and the control groups, the intervention children
      received relatively (in E%) more energy from carbohydrates than the control
      children (p < 0.005), used absolutely (in g) and relatively (in E%) less fat (p <
      0.05) and had a higher PUFA/SAFA ratio in their diet (p < 0.001). Of the 3-year
      old children 93% were caries free, and dental decay was a prevalent in the
      intervention as in the control children. Control children brushed their teeth
      unassisted more often than the intervention children (p < 0.05). The intervention
      fathers also received more energy (in E%) from carbohydrates (p < 0.01), the
      intervention mothers used less fat (p < 0.05) and had a higher PUFA/SAFA ratio in
      the diet (p < 0.05) than the control fathers and mothers, respectively. Dental
      and periodontal health of the intervention and control parents (n = 250, 84%
      attending, mean +/- SD age: 34.2 +/- 54.5 years also showed no differences even
      though the control parents had more commonly last visited a dentist over 3 years
      before this examination (p < 0.05). We conclude that a 29-month period of a low
      saturated-fat, low-cholesterol but high-carbohydrate diet as advocated in the
      STRIP baby trial does not seem to have harmful effects on the oral health of the
      children or their parents. Minor untoward differences had occurred in the dental
      health behavior of the control children and their parents.

PMID- 9165189
TI  - Effect of different chlorhexidine varnish regimens on mutans streptococci levels
      in interdental plaque and saliva.
AB  - The aim of the present study was to evaluate and compare the effects of an
      intensive and a monthly mode of antibacterial varnish application on the levels
      of mutans streptococci (MS) in interdental plaque and whole saliva. Eighty-eight
      healthy schoolchildren (11-13 years) with high scores of salivary MS were
      selected by a screening procedure and randomised into two groups, MS were
      enumerated at all mesial interdental sites of the first permanent molars with the
      aid of a modified chair-side technique, disclosing a total of 161 sites with
      moderate or high colonisation levels. The subjects were treated with a 1%
      chlorhexidine-thymol-containing varnish (Cervitec) either in an intensive mode
      (IM) with 3 applications within a 2-week period or in a monthly mode (MM) during
      a 3-month period. The varnish was applied with a miniball burnisher after the
      teeth had been cleaned interdentally with dental floss and dried with air. Follow
      up samples of saliva and plaque from the interdental areas were collected after
      1, 3 and 6 months. Both groups exhibited a statistically significant (p > 0.05)
      reduction of interdental MS after 1 month when compared with baseline. An
      eliminated MS growth appeared more frequently following the IM compared with the
      MM. After 3 months, a significant reduction compared with baseline was still
      found in the IM group but not in the MM group. No reduction was found in either
      group after 6 months. MS levels in saliva were mainly unaffected at the follow-up
      samplings, with the exception of a slight reduction in the IM group after 1
      month. In conclusion, the results suggest that an intensive mode of chlorhexidine
      thymol varnish application is more effective against interdental MS than the
      monthly mode of application. Bacterial growth should be monitored in a site
      specific way, since interdental reductions were not adequately reflected in whole
      saliva samples.

PMID- 9165190
TI  - A method for the quantitative site-specific study of the biochemistry within
      dental plaque biofilms formed in vivo.
AB  - The study of plaque biofilms in the oral cavity is difficult as plaque removal
      inevitably disrupts biofilm integrity precluding kinetic studies involving the
      penetration of components and metabolism of substrates in situ. A method is
      described here in which plaque is formed in vivo under normal (or experimental)
      conditions using a collection device which can be removed from the mouth after a
      specified time without physical disturbance to the plaque biofilm, permitting
      site-specific analysis or exposure of the undisturbed plaque to experimental
      conditions in vitro. Microbiological analysis revealed plaque flora which was
      similar to that reported from many natural sources. Analytical data can be
      related to plaque volume rather than weight. Using this device, plaque fluoride
      concentrations have been shown to vary with plaque depth and in vitro short-term
      exposure to radiolabelled components may be carried out, permitting important
      conclusions to be drawn regarding the site-specific composition and dynamics of
      dental plaque.

PMID- 9165192
TI  - Effect of a two-solution fluoride mouth rinse on deposition of loosely bound
      fluoride on sound root tissue and remineralization of root lesions in vitro.
AB  - A constant-composition fluoride (F) titration method was used to measure the
      amount of leachable F deposited on root surfaces in vitro by a 1-min rinse with a
      12 mmol/l sodium fluoride (228 micrograms/g F) solution or a two-solution rinse
      that contained 2 mmol/l sodium fluorosilicate (228 micrograms/g total F ) and 10
      mmol/l calcium chloride. The mean +/- standard deviations (n = 3) F uptake from
      the two rinse treatments were 0.70 +/- 0.24 micrograms/cm2 and 3.25 +/- 0.74
      micrograms/cm2, respectively. In a separate experiment, the effects of sodium
      fluoride and the two-solution rinses on remineralization of root lesions were
      evaluated in an in vitro pH cycling model. The results showed that the average
      decrease in mineral loss (delta Z) in the two-solution rinse group (60%) was
      significantly greater than that obtained in the NaF rinse (41%) or the control
      (9%) group.

PMID- 9165191
TI  - Penetration of varnishes into demineralized root dentine in vitro.
AB  - In this paper the penetration of three different varnishes employed in caries
      prevention (Duraphat, Fluor Protector and Cervitec) into demineralized dentine is
      quantified using confocal laser scanning microscopy. The results show that the
      varnish penetration into lesions about 85 microns in depth if for Cervitec about
      35 microns and considerably less for Duraphat and Fluor Protector. The
      penetration is into the dentinal tubules and is influenced by dentinal tubule
      direction. The drying procedure--pretreatment of the dentine--influences the
      penetration, though sizeably only for Cervitec applications. This paper shows
      that varnish penetration into the tissue and presumably 'sealing' tubules
      completely or partly is valuable with respect to root caries prevention and
      hypersensitivity.

PMID- 9165193
TI  - The effect of fluoridated milk on human dental enamel in an in vitro
      demineralization model.
AB  - Fifty-seven sound human permanent premolars were demineralized for 14 days and
      then exposed to six different treatments: group 1, 1 mg/1 fluoride in milk for 7
      days; group 2, 1 mg/l fluoride in milk for 14 days; group 3, 10 mg/l fluoride in
      milk for 7 days; group 4, 10 mg/l fluoride in milk for 14 days; group 5, control
      non-fluoridated milk for 14 days, and group 6, control tap water for 14 days.
      Enamel etch samples were taken and analysed for fluoride and for phosphorus. An
      increase in the enamel surface fluoride content was observed in groups 1-3. A
      statistically significant elevation (p < 0.01) of fluoride content and a
      significant decrease (p > 0.001) of acid solubility were found only in group 4.

PMID- 9165194
TI  - Influence of polymers for use in saliva substitutes on de- and remineralization
      of enamel in vitro.
AB  - A number of polymers which have previously been tested for their applicability as
      thickening agents in saliva substitutes were studied in vitro for their caries
      protective properties. These were: polyacrylic acid, carboxymethylcellulose,
      xanthan gum, guar gum, hydroxyethylcellulose and porcine gastric mucin. The
      polymers were tested for their effects on: (1) growth of hydroxyapatite crystals
      in a supersaturated calcium phosphate solution, (2) dissolution of hydroxyapatite
      crystals in 50 mM acetic acid, pH 5.2 and (3) demineralization and
      remineralization of bovine enamel in a pH-cycling model. Growth of hydroxyapatite
      crystals was strongly inhibited by polyacrylic acid and carboxymethylcellulose at
      very low concentrations (0.005% w/v). Other polymers displayed lower inhibition
      of hydroxyapatite crystal growth. Hydroxyapatite dissolution was inhibited by all
      polymers except by hydroxymethylcellulose and xanthan gum. This occurred both in
      the presence of the polymers as well as after a 30-min preincubation. In the pH
      cycling experiment, bovine enamel specimens with preformed lesions were
      alternately exposed to a demineralization buffer and a remineralization buffer
      containing the polymers hydroxyethylcellulose, carboxymethylcellulose, xanthan
      gum, polyacrylic acid, or porcine gastric mucin. A remineralization buffer
      containing 1 ppm NaF was used as a positive control. Under the experimental
      conditions, the control experiment without additives resulted in a net mineral
      loss (30.6 mumol Ca/cm2 after 14 days of pH cycling). In the presence of 1 ppm
      NaF, a small mineral gain was observed (8.6 mumol/cm2). All polymers largely
      inhibited further demineralization (1.2-12.3 mumol/cm2) except polyacrylic acid
      which, inhibited of its high calcium-binding capacity, caused demineralization,
      especially in the remineralization buffer (17.1 mumol/cm2). In conclusion,
      polymers tested in this study, except the polyacrylic acid, reduced the
      demineralization of enamel in vitro. The precise mechanism of the protective
      effect is not clear but it is speculated that formation of an absorbed polymer
      layer on the hydroxyapatite or enamel surface may provide protection against
      acidic attacks.

PMID- 9165195
TI  - Reproducibility and accuracy of three methods for assessment of demineralization
      depth of the occlusal surface: an in vitro examination.
AB  - This laboratory study of 100 occlusal surfaces investigated the reproducibility
      and accuracy of a visual ranked caries scoring system, an electronic caries
      scoring system (ECM) using a continuous conductance scale, and a radiographic
      ranked caries scoring system. Histological examination of the teeth served as a
      gold standard to validate the ability of each system to assess lesion depth and
      predict softened, demineralized dentine. After training, 3 examiners carried out
      each scoring system on two separate occasions. Kappa values for visual, ECM and
      radiographic ranked scoring systems showed good inter- and intra-examiner
      reproducibility levels and acceptable limits of agreement for ECM readings. When
      scoring systems were tabulated against histological scores there was a high
      correlation between the visual and ECM methods and lesion depth in both enamel
      and dentine, but radiographic examination could not detect enamel caries. When
      compared to the histological scoring, the Spearman correlation coefficients for
      the visual scoring ranged between 0.87 and 0.93, for the ECM between 0.80 and
      0.85 and for the radiographic scoring system between 0.76 and 0.78. No tooth
      scored as visually sound had histological evidence of dentine caries. Soft
      dentine corresponded to demineralization involving the middle third of the
      dentine or more which was related to visual cavity formation or an ECM reading
      above 9 (score 3 or 4). The radiograph was an excellent predictor of soft
      dentine. In conclusion, the new visual system appears promising, but takes time
      to learn. The reproducibility and accuracy for the ECM is acceptable while
      radiographs miss early occlusal lesions.

PMID- 9165196
TI  - Wavelength-dependent fibre-optic transillumination of small approximal caries
      lesions: the use of a dye, and a comparison to bitewing radiography.
AB  - The mere detection of caries lesions is insufficient for optimal treatment
      decision-making. Hence, the aim of this study was to investigate whether
      quantitative information about approximal lesion depth can be obtained from a
      technique based on the wavelength dependency of light propagation and additional
      use of a dye. Another aim was to compare the diagnostic performance of the
      optical technique and bitewing radiography. Measurements were performed on 33
      extracted premolar teeth. Twelve proximal surfaces had white-spot, and 17 had
      discoloured small lesions. Four surfaces were sound. The teeth were
      transilluminated with a single glass fibre at the approximal surface before and
      after dye application. The occlusal surface was imaged with a CCD camera. Light
      in the blue and red part of the electromagnetic spectrum was selected using
      Schott glass filters. Average decadic optical thickness differences, delta bl-rd
      tau eff, were estimated and plotted as a function of normalised lesion depth,
      dhist, established from histological validation by two observers. The Spearman
      rank correlation was rs (delta bl-rd tau eff, dhist) = 0.87 (95% confidence
      interval, CI: 0.74-0.94). A marked increase in average decadic optical thickness
      in the blue part of the electromagnetic spectrum, delta dye tau eff, was observed
      for those lesion that, upon direct visual inspection of the approximal surface,
      clearly showed dye uptake. Bitewing radiographic depth ratings of two observers
      were plotted as a function of dhist. The correlations were rs (dRA,1, dhist) =
      0.62 (95% CI: 0.34-0.80), rs (dRA,2, dhist) = 0.75 (95% CI: 0.54-0.87), and
      between the observers rs (dRA,1, dRA,2) = 0.44 (95% CI: 0.10-0.69). The p values
      of rs (delta bl-rd tau eff, dhist) -rs (dRA1,1, dhist) and rs (delta bl-rd tau
      eff, dhist) -rs (dRA,2, dhist) were p1 = 0.01 and p2 = 0.08, respectively. It was
      concluded that quantitative information about lesion depth can be obtained
      optically. The dye penetrates into only a limited number of caries lesions, in
      which cases dye uptake is detectable in transillumination geometry. Under
      laboratory circumstances the optical technique performs as well as bitewing
      radiography in the diagnosis of small approximal caries lesions.

PMID- 9165197
TI  - Effects of frequency of exposure to iron-sucrose on the incidence of dental
      caries in desalivated rats.
AB  - World Health Organization (WHO) estimates that 2.5 billion people have anemia
      caused by iron deficiency that could be prevented by fortification of food;
      sugar, for example, has been used successfully as a vehicle for dietary iron
      fortification. The inclusion of 88 ppm of iron (as FeSO4) co-crystallized with
      sugar has been shown to reduce the incidence of caries by more than 30% when rats
      are fed 17 meals daily at hourly intervals. The purpose of the present study was
      to determine the influence of varying the number of daily exposures to iron on
      caries in desalivated rats. Four litters of 12 Sprague-Dawley rats were
      desalivated when aged 25 days and caged in a programmed feeder. All animals
      received their essential nutrition by gavage and 17 meals of sucrose daily. In
      Group A, 6 meals contained 88 ppm Fe; in Group B, 3 meals continued iron: Group C
      had 2 meals, and in Group D, no iron was added. The investigation continued for 3
      weeks. Smooth-surface and sulcal (in parentheses) caries scores were: Group A
      60.8 (39.4); Group B 72.4 (41.3); Group C 73.1 (41.3), and Group D 92.9 (49.2).
      Caries scores in all the iron groups were statistically lower than in the control
      group. Severity scores followed a similar pattern. Thus, as few as 2 daily
      exposures to iron-sucrose had a significant effect on caries development;
      therefore the use of iron as a cariostatic agent is worthy of further
      exploration. The concept that two major public health problems could be
      alleviated by the addition of iron to sucrose is indeed attractive.

PMID- 9165199
TI  - Compound allergy. An overview.
AB  - This review defines the term "compound allergy" in the context of new findings,
      and discusses evidence that allergenic reaction products have been identified.
      Material was gathered by searching Index Medicus and the Science Citation Index,
      and reviewing several standard texts. Issues regarding the validity of patch test
      results are addressed and we introduce the term "pseudocompound allergy" to cover
      cases of false-negative patch tests. We present new theories regarding the
      mechanisms by which new allergens are formed and a means of classification.

PMID- 9165198
TI  - Influence of iron alone or with fluoride on caries development in desalivated and
      intact rats.
AB  - Sugar is used as a vehicle for iron fortification in communities where anemia is
      prevalent. The purpose of the present study was to investigate the relationship
      between caries experience and iron concentration in sugar fed to rats subjected
      to a severe cariogenic challenge. Desalivated and intact animals were assigned to
      4 different diet subgroups, 3 receiving iron sucrose (350, 175 and 88 ppm Fe) and
      a control group. The influence of iron sugar combined with 10 ppm F in drinking
      water was explored in an additional study. Iron reduces the incidence of smooth
      surface carries in desalivated rats at concentrations as low as 88 ppm Fe. In
      addition, a combination of iron and fluoride reduced the incidence of dental
      caries in our rats.

PMID- 9165200
TI  - Topical D-vitamins: multiparametric comparison of the irritant potential of
      calcipotriol, tacalcitol and calcitriol in a hairless guinea pig model.
AB  - The irritant potential of calcipotriol, 1 alpha,24-dihydroxyvitamin D3
      (tacalcitol) and 1 alpha,25-dihydroxy-vitamin D3 (calcitriol) was compared in a
      hairless guinea pig model, Randomized, occlusive patch testing for 2 days was
      used. Each group of 8 animals was tested simultaneously with the 3 substances and
      a placebo vehicle. 3 dose levels i.e. 500 micrograms/ml, 50 micrograms/ml and 5
      micrograms/ml were used. Test sites were evaluated at day 2 (2 h after removal of
      the patches) and again at day 3. Evaluation was blinded and based on a multiple
      parameter assessment of skin irritancy, comparing clinical scoring, skin
      perfusion using high resolution laser Doppler image scanning, skin colour (a*,
      Minolta ChromaMeter) and skin thickening (20 MHz ultrasound) indicating oedema.
      Skin biopsies were taken for histological preparation and assessment of epidermal
      hyperplasia. No difference was observed between the irritant potential for
      calcipotriol, tacalcitol and calcitriol based on clinical scoring as well as
      objective non-invasive measuring techniques. All 3 substances showed a dose
      dependent and equal increase in clinical irritation score, cutaneous blood flow,
      skin colour and epidermal hyperplasia. The cutaneous inflammatory reaction was
      dominated by vasodilation and increased cutaneous perfusion. Oedema formation was
      only seen at the highest dosages tested. Skin barrier damage was not induced as
      TEWL remained unaffected. The hairless guinea pig appears a valid model to test
      irritancy of topical D-vitamins since the same profile of irritancy was
      previously established in humans for 2 of the compounds tested, calcitriol and
      calcipotriol.

PMID- 9165201
TI  - Occupational allergic contact dermatitis from 2,3-epoxypropyl trimethyl ammonium
      chloride (EPTMAC) and Kathon LX in a starch modification factory.
AB  - 2,3-epoxypropyl trimethyl ammonium chloride (EPTMAC) is used in the production of
      cationic starch (CS) for the paper industry. It has been shown to be a sensitizer
      in guinea pigs, but cases of human sensitization are few. 4 workers were
      previously sensitized to the substance in a Finnish plant. This report describes
      3 process men from another plant examined because of recurring dermatitis. 18
      workers were involved in production, and had free access to all work sites. 3
      process men, whose work involved drying the CS, had dermatitis, although they had
      only occasional contact with the cationizing chemical. 2 were already verified to
      be allergic to EPTMAC and had had variable dermatitis for 8-12 years. One had had
      dermatitis on his face for 1 year. Patch testing with a dilution series (1%,
      0.5%, 0.2%, 0.1% pet.) confirmed their allergy to the cationizing chemical
      containing EPTMAC, but tests with CS were negative. In addition, 2 had contact
      allergy to Cl+ Me-isothiazolinone from contact with Kathon LX used as a slimicide
      in the process. In long-standing (years) recurrent dermatitis, re-examination of
      patients with verified exposure history and skin test is necessary. In line with
      our previous study, sampling the process materials, maintenance work and
      contamination of work sites and gloves caused sensitization. The results also
      confirm that EPTMAC is a strong human contact sensitizer. 0.2%-0.5% pure EPTMAC
      in pet. seems to be the optimal patch test concentration.

PMID- 9165202
TI  - Extraction of mercaptobenzothiazole compounds from rubber products.
AB  - At evaluation of contact dermatitis caused by solid material, patch testing is
      usually performed with the material as such and with extracts of it. In this
      study, optimization of the extraction technique monitored by quantitative HPLC
      analysis of the extracted haptens is described for mercaptobenzothiazole
      derivatives. Several solvents with different properties are included. Acetone has
      traditionally been a solvent widely used for the extraction of organic haptens
      from solid products. However, acetone and other ketones are not inert solvents.
      The rubber accelerators 2-(4-morpholinyl mercapto) benzothiazole (MMBT) and N
      cyclohexyl-2-benzothiazyl sulfenamide (CBS) react with acetone, yielding 2 new
      compounds, which were isolated and characterised by NMR and MS. For the
      extraction of solid rubber products, methyl tert-butyl ether (MTBE) was found to
      be a more suitable solvent which is unreactive to most common haptens.

PMID- 9165203
TI  - Contact allergy to oxidized d-limonene among dermatitis patients.
AB  - d-Limonene, obtained as a by-product from the citrus juice industry, was
      introduced on the market as a more environmentally friendly defatting and
      cleaning agent than the traditionally used organic solvents. Autoxidation of d
      limonene readily occurs to give a variety of oxygenated monocyclic terpenes that
      are strong contact allergens. The aim of the present study was to investigate the
      prevalence of contact allergy to air exposed d-limonene among dermatitis
      patients. A fraction consisting of d-limonene hydroperoxides was also tested.
      Screening with oxidized d-limonene will detect cases of allergic contact
      dermatitis. Additional cases were detected when testing with the fraction of
      limonene hydroperoxides. The proportion of positive patch test reactions to
      oxidized d-limonene was comparable to that seen for several of the allergens
      within the standard series. An increased use of d-limonene containing allergenic
      oxidation products in industry where high concentrations are used, as well as in
      domestic exposure, might result in contact sensitization and dermatitis. Patients
      reacting to d-limonene often reacted to fragrance mix, balsam of Peru and
      colophony in the standard series.

PMID- 9165204
TI  - Results of patch testing with a special series of rubber allergens.
AB  - The purpose of this study was to examine the results of patch testing with the
      rubber components on a standard screening tray and compare them with the results
      of testing with a special series of 27 rubber components (rubber tray). 1670
      patients were patch tested with the screening tray and 317 of these were also
      tested with the rubber tray. 16% of those tested with the rubber tray had a
      positive response to at least 1 of the rubber allergens on the screening tray and
      22% had a positive response to at least 1 of the allergens on the rubber tray.
      The most common positive response to the rubber tray allergens was to
      tetramethylthiuram monosulfide. There were no responses to 3 of the components on
      the rubber tray and there was only 1 positive response to a further 4 components.
      The diagnostic test characteristics of the rubber components on the screening
      tray were examined using the rubber tray as the gold standard. The sensitivity of
      the screening tray was 94%, specificity 51%, positive predictive value 87% and
      negative predictive value 71%. Of the 317 tested, 11% were found to have a
      positive to a substance on the rubber tray that was not evident from the results
      of the screening tray.

PMID- 9165206
TI  - Skin disorders in ship's engineers exposed to oils and solvents.
AB  - Ship's engineers are exposed to mineral oil and solvents in their work. This
      study was intended to investigate if the ship's engineers had an increased
      prevalence of skin disorders and whether any such increased risk could be linked
      to exposure to mineral oils and solvents. A self-administered questionnaire was
      sent to 700 male seamen from 3 Norwegian ferry countries. Of the 492 respondents,
      169 were currently working as ship's engineers and 295 had never worked as ship's
      engineers. The outcomes eczema, acne, dry skin, and dermatitis and hand
      dermatitis were defined from the questionnaire. Prevalences of these skin
      disorders were compared between the groups. Logistic regression was used to
      elucidate explanatory variables further. When comparing current ship's engineers
      with those who had never worked as ship's engineers, the crude prevalence ratios
      were 1.7 (95% CI 1.1-2.7) for dry skin, 1.7 (95% CI 1.1-2.5) for any dermatitis,
      1.3 (95% CI 0.66-2.67) for acne and 1.2 (CI 0.61-2.27) for eczema. The risk of
      these symptoms increased for the engineers in the regression analysis, after
      controlling for age, self-reported use of Stoddard solvent, and the use of fuel
      oil as hand cleansing agent. The increased prevalence of skin disorders found
      among ship's engineers in this investigation may be explained by direct contact
      with mineral oils and solvents.

PMID- 9165205
TI  - Epidemiological significance of bufexamac as a frequent and relevant contact
      sensitizer.
AB  - Bufexamac-containing ointments and creams are widely used by many patients with
      eczematous disorders as an alternative to topical corticosteroids. Recent studies
      provide evidence of a notable prevalence of contact sensitization in patch test
      populations. The aim of this study was to assess the frequency of use of this
      topically-applied drug by eczema patients in general, and to evaluate its
      potential to cause allergic contact reactions. 500 routinely patch tested
      patients (f:m = 377:123) were tested with bufexamac 5% and Parfenac ointment (the
      only commercial product available in Austria) in addition to the standard and
      other series of the German Contact Dermatitis Group. The packaging of the
      commercial product was shown to the entire study population, to decide whether or
      not they had ever used this product. In addition, their general practitioner was
      contacted to verify the anamnestic data. A total of 30 patients agreed that they
      had definitely used bufexamac, 5 others having probably applied it. The
      indication for and the duration of treatment were noted. Positive and relevant
      patch test reactions to bufexamac, as well as the bufexamac-containing ointment,
      were seen in 20 out of these 35 patients (57%), and sensitization occurred even
      after short-term application. Our study demonstrates that bufexamac has to be
      assumed to be a topical drug with a very high sensitization rate in an unselected
      patch test population (4% of 500 patients), and should therefore be added to the
      standard series.

PMID- 9165207
TI  - Allergic contact dermatitis from pyoctanin.
AB  - Although pyoctanin is widely used in medicine, there are hardly any reports of
      contact allergy to it. Most reports of side-effects refer to irritant reactions
      after topical application. We describe 2 patients who developed pyoctanin contact
      dermatitis after long-term application on damaged skin. Positive patch test
      results down to concentrations of 0.0025% and 0.05% aqueous pyoctanin solution,
      respectively, were found.

PMID- 9165208
TI  - Fixed drug eruption due to acyclovir.

PMID- 9165209
TI  - Patch testing versus history in poison ivy/oak dermatitis.

PMID- 9165210
TI  - Occupational depigmentation from dinoterbe.

PMID- 9165211
TI  - Occupational contact dermatitis from ethylenediamine in a wire-drawing lubricant.

PMID- 9165212
TI  - Latex contact urticaria presenting as facial swelling in a motor mechanic.

PMID- 9165213
TI  - Contact dermatitis due to levobunolol in eyedrops.

PMID- 9165214
TI  - Contact dermatitis due to octyldodecanol in clotrimazole cream.

PMID- 9165215
TI  - The pancreatic beta-cell as a fuel sensor: an electrophysiologist's viewpoint.
AB  - The pancreatic beta cell serves as the fuel sensor of the entire body and
      controls, via secretion of the hypoglycaemic hormone insulin, the blood glucose
      concentrations within narrow limits by regulation of glucose uptake and release.
      During the last 30 years, a combination of biochemical and ultrastructural
      approaches has resulted in dramatic progress in the understanding of the
      processes by which glucose and other nutrients modulate the release of insulin.
      The beta cells have also been investigated using electrophysiological techniques
      and were thus found to be electrically excitable and to undergo complex changes
      in their membrane potential when exposed to glucose and other stimulators of
      secretion. The application of the patch-clamp technique to the pancreatic islet
      preparations has revolutionized the understanding of how bioelectrical processes
      participate in the fuel-sensing of the beta cell. An important achievement was
      the identification of an ATP-sensitive K(+)-channel as the resting and glucose
      sensitive membrane conductance of the beta cell. This channel also constitutes
      the target of the hypoglycaemic sulphonylureas: a group of compounds which have
      been used successfully in the treatment of insulin-dependent diabetes mellitus
      for several decades.

PMID- 9165216
TI  - Alteration of Na,K-ATPase isoenzymes in diabetic cardiomyopathy: effect of
      dietary supplementation with fish oil (n-3 fatty acids) in rats.
AB  - Diabetic cardiomyopathy has been associated with a decrease in Na,K-ATPase
      activity and expression, as well as alterations in membrane lipid composition.
      The aim of this study was twofold: 1) to document in rats the effect of
      streptozotocin-induced diabetes on myocardial Na,K-ATPase and fatty acids, and 2)
      to evaluate the potential effect of a dietary supplementation with fish oil (n-3
      fatty acids) on the streptozotocin-induced changes. Assays were performed in
      purified cardiac plasma membranes to determine Na,K-ATPase activity, expression
      of the different alpha- and beta-subunits of Na,K-ATPase, and the fatty acid
      content of total phospholipids. Relative abundance of the mRNAs encoding the
      alpha 1, alpha 2 and beta 1 isoforms was studied by Northern blot analysis.
      Results demonstrated that diabetes significantly decreased activities of alpha 1
      and alpha 2 isoforms and mRNA levels of alpha 2 and beta 1 isoforms, and, at the
      protein level, increased alpha 1-isoforms and decreased both alpha 2- and beta 1
      isoforms. Changes in fatty acid content of the membrane were consistent with
      inhibition of desaturase. Fish-oil supplementation produced an increase in
      membrane incorporation of eicosapentaenoic acid. It also increased the level of
      beta 1-isoforms and restored the activity of the alpha 2-isoenzyme without
      significant changes in the level of alpha 1- and alpha 2-isoforms. Northern blot
      analysis showed no effect of fish oil supplementation. Experimental diabetes and
      prevention by the fish oil rich (n-3 fatty acids) diet induced specific effects
      on the activity and expression of alpha and beta Na,K-ATPase subunit isoforms.
      These studies suggest that fish oil therapy may be effective in preventing some
      of the adverse consequences of diabetes.

PMID- 9165217
TI  - Association of diabetic neuropathy with Na/K ATPase gene polymorphism.
AB  - Diabetes mellitus induces a decrease in Na/K ATPase activity in man and animals,
      and this decrease plays a role in the development of diabetic neuropathy. Na/K
      ATPase is encoded by various genes, of which the ATP1 A1 gene is expressed
      predominantly in peripheral nerves and in erythrocytes. To investigate whether a
      polymorphism in the Na/K ATPase genes could explain the predisposition of some
      patients with insulin-dependent diabetes mellitus (IDDM) to develop
      polyneuropathy, a restriction fragment length polymorphism (RFLP) of the ATP1 A1
      gene was studied together with erythrocyte Na/K ATPase activity in 81 Caucasian
      patients with more than 10 years' duration of IDDM. Associations with diabetic
      neuropathy, retinopathy and nephropathy were sought. Digestion of the first
      intron of the ATP1 A1 gene by the Bgl II restriction enzyme revealed a dimorphic
      allelism. Frequency of the restricted allele was 0.18 in this selected series
      (however, it was 0.10 in representative samples of IDDM patients and of normal
      subjects in our area). Mean erythrocyte Na/K ATPase activity was lower in
      diabetic patients than in 42 control subjects (292 +/- 10, vs 402 +/- 13 nmol
      Pi.mg protein-1.h-1, p < 0.0001) and was not related to HbA1c value or to
      diabetes duration. It was lower in the group of the 28 patients bearing the
      restricted allele (241 +/- 10 vs 319 +/- 11 nmol Pi.mg protein-1.h-1, p <
      0.0001). Neuropathy was absent in 50 patients, mild in 15 and severe in 16. When
      classified accordingly the three groups of patients did not differ with respect
      to sex, age and duration of diabetes. The respective frequency of the restricted
      allele among the groups was 10, 73 and 81%, (p < 0.0001) and mean erythrocyte
      Na/K ATPase activity was respectively: 322 +/- 10.7 nmol Pi.mg protein-1.h-1, 268
      +/- 15 and 229 +/- 17, (p < 0.001). A borderline association between renal status
      or retinal status and repartition of polymorphism and a borderline correlation
      between renal status and Na/K ATPase activity were found, but significance
      disappeared after checking for the presence or absence of neuropathy. IDDM
      patients bearing the ATP1 A1 variant detected by Bgl II RFLP are much more
      frequently affected by neuropathy (relative risk 6.5, with 95% CI 3.3-13).
      Identification of this risk factor may help to prevent this complication. It is
      suggested that the restricted allele is in linkage disequilibrium with a genomic
      mutation allowing diabetes to induce a greater impairment of Na/K ATPase activity
      which could in turn favour the development of neuropathy.

PMID- 9165218
TI  - Effect of exogenous hyperinsulinaemia on atherogenesis in cholesterol-fed
      rabbits.
AB  - To examine the hypothesis that hyperinsulinaemia promotes atherosclerosis,
      cholesterol-fed rabbits were injected subcutaneously with 6 i.u. of human insulin
      (n = 16) or placebo (n = 20) daily for 24 weeks; injection of insulin resulted in
      hyperinsulinaemia for up to 16 h after injection. Compared to placebo rabbits,
      insulin-treated rabbits had higher levels of insulin antibodies in plasma,
      similar levels of intermediate density, low density and high density lipoprotein
      cholesterol and similar activities of hepatic and lipoprotein lipase in post
      heparin plasma, but lower levels of plasma C-peptide, blood glucose, postprandial
      plasma triglycerides, plasma cholesterol and very low density lipoprotein
      cholesterol. On univariate analysis, with and without adjustment for differences
      in plasma cholesterol levels between the two groups, there were no significant
      differences in extent or severity of atherosclerosis between insulin and placebo
      rabbits. Furthermore, after combining the results from all the rabbits to examine
      plasma insulin levels and the other variables mentioned above as predictors of
      atherosclerosis severity, plasma insulin level was not a predictor, on univariate
      or multiple linear regression analysis; the first ranked independent predictors
      were postprandial intermediate density lipoprotein cholesterol in the arch, and
      postprandial plasma triglyceride in both the thoracic and abdominal aorta. These
      results suggest that exogenous hyperinsulinaemia does not promote atherogenesis
      in cholesterol-fed rabbits, but that postprandial levels of intermediate density
      lipoprotein cholesterol or plasma triglycerides may be involved in atherogenesis.

PMID- 9165219
TI  - High glucose level inhibits capacitative Ca2+ influx in cultured rat mesangial
      cells by a protein kinase C-dependent mechanism.
AB  - In cultured mesangial cells (MC), capacitative Ca2+ influx via store-operated
      channels (SOC) is potentiated by agents that release Ca2+ from intracellular
      stores, and inhibited by protein kinase C (PKC). Cells grown under high glucose
      conditions, as a model of the diabetic microenvironment, display reduced Ca2+
      signalling in response to vasoconstrictors, probably due to downregulation by
      elevated PKC activity. Since SOC might be relevant to this phenomenon, we
      assessed Ca2+ influx by microfluorometry of fura-2-loaded rat MC cultured for 5
      days in normal (5.5 mmol/l, NG) or high glucose (30 mmol/l, HG). The addition of
      1-10 mmol/l Ca2+ to NG cells equilibrated in Ca(2+)-free media induced an
      immediate Ca2+ influx with a free cytosolic Ca2+ ([Ca2+]i) plateau of 155 +/- 50
      and 318 +/- 114 nmol/l, respectively. Basal influx was reduced to 88 +/- 8 and
      145 +/- 17 nmol/l [Ca2+]i (1-10 mmol/l Ca2+, p < 0.01) by 30 mmol/l D-glucose.
      This effect of HG was confirmed by Mn2+ quenching of fura-2, indicating reduced
      entry of divalent cations via the capacitative pathway. Equimolar L-glucose had
      no effect on Ca2+ influx, consistent with a non-osmotic mechanism. Arginine
      vasopressin (10 mumol/l) elicited weaker release of stored Ca2+ and subsequent
      influx in HG cells (191 +/- 33 vs 153 +/- 24 nmol/l, 400 +/- 76 vs 260 +/- 33
      nmol/l, 1-10 mmol/l Ca2+, NG/HG, p < 0.05). To examine the involvement of PKC in
      the effect of HG on capacitative Ca2+ influx, the enzyme was activated or
      downregulated by treatment with 0.1 mumol/l phorbol myristate acetate (PMA) for 3
      min or 24 h, respectively. PMA acutely inhibited Ca2+ influx in NG cells, while
      PKC downregulation restored it in HG cells. Similarly, the PKC inhibitors
      staurosporin or H-7 normalized SOC activity in HG cells. In summary, impairment
      of Ca2+ influx via SOC by HG is one mechanism of the reduced MC [Ca2+]i
      responsiveness to vasoconstrictors. This event is mediated by PKC and may
      contribute to the glomerular haemodynamic changes in the initial stages of
      diabetes mellitus.

PMID- 9165220
TI  - Identification of four trp1 gene variants murine pancreatic beta-cells.
AB  - Insulin secretion is stimulated by glucose, hormones and neurotransmitters. Both
      activation of a non-selective cation current and activation of a Ca2+ current in
      response to depletion of intracellular Ca2+ stores have been suggested to play a
      role in this stimulation. The properties of these currents resemble those
      reported for the Drosophila genes trp and trpl. Using the reverse transcription
      polymerase chain reaction and Northern blot analysis we found that of the six
      mammalian trp-related genes (trp1-6), only trp1 was expressed at high levels in
      the mouse insulinoma cell line MIN6. We cloned the murine homologue of human trp1
      from MIN6 cells and identified four variants (alpha, beta, gamma and delta),
      generated by alternative splicing near the N-terminus of the protein. In vitro
      translation showed that only the alpha and beta splice variants are efficiently
      expressed. The beta variant is the dominant form in MIN6 cells (and probably in
      mouse pancreatic islets), whereas the alpha variant is the major type in the
      mouse brain. The beta variant showed 99% identity to the human homologue at the
      amino acid level.

PMID- 9165221
TI  - Increased mitogen-activated protein kinase expression and activity in white
      adipose tissue of ventromedial hypothalamus-lesioned rats.
AB  - Ventromedial hypothalamus lesions in rats induce hyperphagia and
      hyperinsulinaemia associated with a rapid growth of white adipose tissue
      resulting in massive obesity. It has been shown previously that at an early stage
      after the lesion, during the dynamic phase of obesity, the white adipose tissue
      is hyper-responsive to insulin. In the present work, we show that the effects of
      insulin on the autophosphorylation of the insulin receptor and on its tyrosine
      kinase activity towards endogenous substrates are similar in intact adipocytes of
      control and ventromedial hypothalamus lesioned rats. One week after the lesion,
      the expression of phosphatidylinisitol 3-kinase and RAF-1 kinase, evaluated by
      Western-blotting, was similar in control and ventromedial hypothalamus lesioned
      rats. In contrast, an important increase in the expression of extracellular
      signal regulated kinase 1 protein was observed in white adipose tissue of
      ventromedial hypothalamus lesioned compared to control animals. No difference in
      the expression of extracellular signal regulated kinase 1 mRNA was observed in
      adipose tissue of control and ventromedial hypothalamus lesioned rats, suggesting
      that a posttranscriptional mechanism is involved in the over-expression of
      extracellular signal regulated kinase 1. The kinase activity of extracellular
      signal regulated kinase 1 and 2 is also markedly increased in adipocytes of
      ventromedial hypothalamus lesioned compared to control rats, both in the basal
      state and after insulin stimulation. Six weeks after the ventromedial
      hypothalamus lesion, this increase in mitogen-activated protein kinase expression
      and activity was still observed in adipocytes of ventromedial hypothalamus
      lesioned rats. These results suggest that an early and sustained increase in the
      expression and activity of mitogen-activated protein kinase may participate in
      the development of white adipose tissue in ventromedial hypothalamus lesioned
      rats.

PMID- 9165222
TI  - Abnormal myocardial kinetics of 123I-heptadecanoic acid in subjects with impaired
      glucose tolerance.
AB  - Increased triglyceride accumulation has been observed in the diabetic heart, but
      it is not known whether the abnormalities in myocardial fatty acid metabolism
      differ between insulin-dependent (IDDM) and non-insulin-dependent (NIDDM)
      diabetic patients or whether they are present even prior to overt diabetes.
      Therefore, we studied myocardial fatty acid kinetics with single-photon emission
      tomography using 123I-heptadecanoic acid (HDA) in four groups of men: impaired
      glucose tolerance (IGT) (n = 13, age 53 +/- 2 years, mean +/- SEM), IDDM (n = 8,
      age 43 +/- 3 years), NIDDM (n = 10, age 51 +/- 2 years) and control subjects (n =
      8, age 45 +/- 4 years). Echocardiography and myocardial perfusion scintigraphy
      (IGT and NIDDM groups) were performed to study cardiac function and flow. In the
      IGT subjects, myocardial HDA beta-oxidation index was reduced by 53% (4.6 +/- 0.4
      vs 9.7 +/- 1.0 mumol .min-1.100 g-1, p < 0.01) and HDA uptake by 34% (3.7 +/- 0.2
      vs 5.6 +/- 0.3% of injected dose 100g, p < 0.01) compared with the control
      subjects. The fractional HDA amount used for beta-oxidation was lower in the IGT
      compared with the control subjects (43 +/- 4 vs 61 +/- 4%, p < 0.05). NIDDM
      patients also tended to have a lowered HDA beta-oxidation index, whereas IDDM
      patients had similar myocardial HDA kinetics compared to the control subjects.
      Myocardial perfusion imaging during the dipyridamole-handgrip stress was normal
      both in the IGT and NIDDM groups, indicating that abnormal myocardial perfusion
      could not explain abnormal fatty acid kinetics. In conclusion, even before
      clinical diabetes, IGT subjects show abnormalities in myocardial fatty acid
      uptake and kinetics. These abnormalities may be related to disturbed plasma and
      cellular lipid metabolism.

PMID- 9165223
TI  - Incidence of childhood diabetes mellitus in Yorkshire, northern England, is
      associated with nitrate in drinking water: an ecological analysis.
AB  - The relationship between the incidence of childhood-onset insulin-dependent
      diabetes mellitus and levels of nitrate in drinking water in the former Yorkshire
      Regional Health Authority was investigated by means of an ecological analysis. A
      population-based register contributed 1797 0-16-year-olds diagnosed with diabetes
      between 1978 and 1994. Nitrate data were based on 9330 samples of drinking water
      tested between 1990 and 1995 in 148 water supply zones, for which 1991 census
      small area statistics were taken on population density, ethnicity and socio
      economic status. Diabetes incidence was positively associated with raised mean
      nitrate levels with a standardised incidence ratio of 115 in zones with greater
      than 14.85 mg.1-1 (chi2 = 26.81, 1 df, p < 0.001). Significant negative trends
      were found between standardised incidence ratios and proportion of non-whites in
      the population (chi2 = 33.57, 1 df, p < 0.001), childhood population density
      (chi2 = 30.81, 1 df, p < 0.001) and the Townsend deprivation score (chi2 = 33.89,
      1 df, p < 0.001). Poisson regression modelling, adjusting for the other factors,
      showed a significant increase in relative incidence rate ratio from a baseline of
      1 at nitrate levels below 3.22 mg.1-1 to 1.27 (95% confidence interval 1.09,
      1.48) for mean nitrate levels above 14.85 mg.1-1. An association between higher
      nitrate levels in domestic drinking water and incidence of childhood diabetes has
      been demonstrated. This was not explained by the ethnic composition of the
      population, population density or socioeconomic status. Nitrate in drinking water
      may be a precursor of chemicals which are toxic to the pancreas.

PMID- 9165224
TI  - Insulin mediators in man: effects of glucose ingestion and insulin resistance.
AB  - Insulin mediators (inositol phosphoglycans) have been shown to mimic insulin
      action in vitro and in intact mammals, but it is not known which mediator is
      involved in insulin action under physiological conditions, nor is it known
      whether insulin resistance alters the mediator profile under such conditions. We
      therefore investigated the effects of glucose ingestion on changes in the
      bioactivity of serum inositol phosphoglycan-like substances (IPG) in healthy men
      and insulin resistant (obese, non-insulin-dependent diabetic) men. Two classes of
      mediators were partially purified from serum before and after glucose ingestion.
      The first was eluted from an anion exchange resin with HCl pH 2.0, and
      bioactivity was determined by activation of pyruvate dehydrogenase in vitro. The
      second was eluted with HCl pH 1.3, and bioactivity was determined by inhibition
      of cyclic AMP-dependent protein kinase. In healthy men, the bioactivity of the pH
      1.3 IPG was not altered by glucose ingestion, whereas bioactivity of the pH 2.0
      IPG increased to approximately 120% of the pre-glucose ingestion value at 60-240
      min post-glucose ingestion (p < 0.05 vs pre-glucose). There was no change in
      either IPG after glucose ingestion in the insulin-resistant group. These data
      suggest that the pH 2.0 IPG plays an important role in mediating insulin's effect
      on peripheral glucose utilization in man under physiological conditions. The data
      further show, for the first time, a defective change in the bioactivity of an
      insulin mediator isolated from insulin-resistant humans after hyperinsulinaemia,
      suggesting that inadequate generation/release of IPGs is associated with insulin
      resistance.

PMID- 9165226
TI  - Activated platelets in subjects at increased risk of IDDM. DENIS Study Group.
      Deutsche Nikotinamid Interventionsstudie.
AB  - Activated platelets respond to activated leukocytes and endothelial cells via
      adhesion molecules linking inflammation and thrombosis. Platelets of recent-onset
      insulin-dependent diabetic (IDDM) patients have been shown to be activated
      independent of metabolic control. This study evaluates the levels of circulating
      activated platelets exposing adhesion molecules in healthy subjects at increased
      risk of IDDM (surface markers were: P-selectin (CD62), thrombospondin, lysosomal
      GP53 (CD63). From the DENIS and the ENDIT screening programmes 19 identified
      islet cell antibody positive (titre > or = 20 Juvenile Diabetes Foundation units)
      first degree relatives of IDDM patients (male/female 9/10; age 22 +/- 15 years;
      body mass index (BMI): 20.0 +/- 4.3 kg/m2) with clearly normal metabolism (HbA1:
      6.1 +/- 0.8%; fasting blood glucose: 4.95 +/- 0.67 mmol/l) were available for
      this investigation. Platelet CD62 as well as thrombospondin and CD63 expression
      were determined by flow cytometry. We matched 50 normal volunteers for age (29 +/
      6 years), anthropometric measures (male/female 26/24; BMI: 22.3 +/- 2.8 kg/m2)
      and metabolic parameters (HbA1: 5.8% +/- 0.3; fasting blood glucose: 4.41 +/-
      0.53 mmol/1) served as control subjects. The mean number of CD62+ platelets was
      increased 3.2-times in prediabetic patients: 1.94 x 2.91 (+/- 1) vs 0.60 x 1.83
      (+/- 1%), p < 0.0001. Thrombospondin+ and CD63+ platelet levels were
      concomitantly increased (1.45 x 2.38( +/- 1)/5.97 x 2.89 (+/- 1)% vs 0.52 x 2.01
      (+/-1)/1.64 x 2.26 (+/-1)%, p < 0.0001 for both comparisons). Thus, intravasal
      platelet activation is already present in potentially prediabetic subjects
      representing an antecedent, potentially pathogenic feature of IDDM.

PMID- 9165225
TI  - Altered immune response to insulin in newly diagnosed compared to insulin-treated
      diabetic patients and healthy control subjects.
AB  - Insulin-dependent diabetes mellitus (IDDM) is the result of a T-cell mediated
      autoimmune beta-cell destruction, which is accompanied by autoantibodies. We
      analysed the cellular and humoral immune response to insulin and insulin peptides
      in patients with recent-onset IDDM, IDDM patients treated with insulin, non
      diabetic first degree relatives and unrelated control subjects. There were no
      differences in T-cell reactivity to whole insulin or insulin peptides in general
      between age-matched groups of IDDM patients, relatives or healthy control
      subjects. In contrast to investigations in NOD mice, no immunodominant or disease
      specific insulin peptide could be identified. Surprisingly, a positive
      correlation of T-cell responses to insulin with age was noticed (p < 0.005). This
      resulted in an inverse relation of insulin autoantibodies (IAA) and insulin
      reactive T-cells (p < 0.001) together with the well-described negative
      correlation of IAA with age. Interestingly, insulin-treated patients differed
      from age-matched recent-onset IDDM patients: first, simultaneous immune
      recognition of insulin with T-cells and IAA was only seen in patients treated for
      6 months with insulin; second, insulin-treated patients rarely responded to whole
      insulin; third, they displayed less determinant spreading, and finally,
      recognition of multiple insulin peptides was not accompanied by crossreactivity
      to whole insulin. These distinct observations in insulin-treated IDDM patients,
      together with the inverse correlation between humoral and cellular responses to
      insulin, may result from activation or modulation of different T-cell subsets,
      and may be of relevance to insulin therapy trials, in which selective activation
      of non-destructive T-cell subsets may be a key to successful intervention.

PMID- 9165227
TI  - High density lipoprotein apolipoprotein AI kinetics in NIDDM: a stable isotope
      study.
AB  - High density lipoprotein (HDL) kinetics were studied by infusing [5,5,5-2H3]
      leucine in five subjects with normal glucose tolerance and eight patients with
      non-insulin-dependent diabetes mellitus (NIDDM) with poor metabolic control
      (HbA1c = 8.16 +/- 1.93%) (mean +/- SD). HDL were modelled as a single compartment
      since no kinetic differences were observed between HDL2 and HDL3 subclasses.
      Plasma apolipoprotein AI (apo AI) concentration was significantly lower in NIDDM
      patients (96.1 +/- 12.1 vs 124.4 +/- 13.1 mg.dl-1, p < 0.01). HDL composition was
      altered in NIDDM, as an increase in HDL-triglyceride and a decrease in HDL
      cholesterol, negatively correlated (r = 0.780, p < 0.01). The mean fractional
      catabolic rate (FCR) of apo AI-HDL was significantly higher (0.39 +/- 0.16 vs
      0.21 +/- 0.06 d-1, p < 0.05) while the apo AI-HDL absolute production rate was
      not significantly greater (13.6 +/- 5.1 vs 12.0 +/- 4.2 mg.kg-1.d-1) in diabetic
      patients compared to normal subjects. There were significant correlations between
      apo AI-HDL FCR and plasma apo AI concentration (r = -0.580, p < 0.05), plasma
      triglycerides (r = 0.839, p < 0.0001) or HDL-triglyceride levels (r = 0.597, p <
      0.05). No correlation was observed between apo AI-HDL FCR and HbA1c or HDL
      cholesterol level. These data support the view that the decrease in plasma apo AI
      level in patients with NIDDM is due to an increase of apo AI-HDL FCR, which may
      itself be related to changes in HDL composition.

PMID- 9165228
TI  - E-selectin plasma concentration is influenced by glycaemic control in NIDDM
      patients: possible role of oxidative stress.
AB  - Although elevated levels of soluble E-selectin and intercellular cell adhesion
      molecules-1 (ICAM-1) have been reported in non-insulin-dependent diabetes
      mellitus (NIDDM), it is not clear by what mechanism this elevation occurs and
      whether or not it is related to glycaemic control. In this study we analyse: 1)
      the relation of glycaemic control with the concentrations of E-selectin, vascular
      cell adhesion molecules-1 (VCAM-1) and ICAM-1 in NIDDM patients: 2) whether
      metabolic control can affect the oxidative stress (as measured by plasma
      hydroperoxide concentration and susceptibility of LDL to in vitro oxidation) and
      hence the adhesion molecule plasma concentrations. Thirty-four (19 males and 15
      females) poorly controlled NIDDM patients were studied. All parameters were
      evaluated at the beginning of the study and after 90 days of dietary and
      pharmacological treatment. The treatment decreased HbA1c (p < 0.001), E-selectin
      (p < 0.001), plasma hydroperoxides (p < 0.003) and the susceptibility of LDL to
      in vitro oxidation (lag phase) (p < 0.0001). Before treatment HbA1c, lag phase
      and lipid hydroperoxides correlated with E-selectin plasma concentration (r =
      0.51, -0.57 and 0.54, respectively, p < 0.01). There was also a correlation
      between HbA1c and lag phase (p < 0.01) and between HbA1c and lipid hydroperoxides
      (p < 0.01). In addition, the variations of HbA1c, lag phase and lipid
      hydroperoxide values correlated with those for E-selectin concentration after 90
      days' treatment (r = 0.54, -0.64 and 0.61, respectively, p < 0.01). In multiple
      linear correlation analysis, however, the partial correlation coefficients of
      HbA1c (basal and variations) with E-selectin concentration (basal and variations)
      fell to non-significant values (r = 0.12 and 0.25, respectively) when LDL lag
      phase and plasma hydroperoxides were kept constant. The results indicate that the
      improvement of metabolic control in NIDDM patients is associated with a decrease
      of E-selectin plasma levels; they also suggest that glycaemic control per se is
      not directly implicated in determining E-selectin plasma concentration; glycaemic
      control could affect E-selectin concentration through its effect on oxidative
      stress.

PMID- 9165229
TI  - Regional variation in adipose tissue insulin action and GLUT4 glucose transporter
      expression in severely obese premenopausal women.
AB  - Insulin action and GLUT4 expression were examined in adipose tissue of severely
      obese premenopausal women undergoing gastrointestinal surgery. Fat samples were
      taken from three different anatomical regions: the subcutaneous abdominal site,
      the round ligament (deep abdominal properitoneal fat), and the greater omentum
      (deep abdominal intraperitoneal fat). The stimulatory effect of insulin on
      glucose transport and the ability of the hormone to inhibit lipolysis were
      determined in adipocytes isolated from these three adipose depots. Insulin
      stimulated glucose transport 2-3 times over basal rates in all adipocytes.
      However, round ligament adipose cells showed a significantly greater
      responsiveness to insulin when compared to subcutaneous and omental adipocytes.
      Round ligament fat cells also displayed the greatest sensitivity and maximal
      antilipolytic response to insulin. We also investigated whether regional
      differences in fat cell insulin-stimulated glucose transport were linked to a
      differential expression of the GLUT4 glucose transporter. GLUT4 protein content
      in total membranes was 5 and 2.2 times greater in round ligament adipose tissue
      than in subcutaneous and omental fat depots, respectively. Moreover, GLUT4 mRNA
      levels were 2.1 and 3 times higher in round ligament than in subcutaneous or
      omental adipose tissues, respectively. Adipose tissue GLUT4 protein content was
      strongly and negatively associated (r = -0.79 to -0.89, p < 0.01) with the waist
      to-hip ratio but not with total adiposity. In conclusion, these results
      demonstrate the existence of site differences in adipose tissue insulin action in
      morbidly obese women. The greater insulin effect on glucose transport in round
      ligament adipocytes was associated with a higher expression of GLUT4 when
      compared to subcutaneous abdominal and omental fat cells. Moreover, despite the
      regional variation in GLUT4 expression, an increased proportion of abdominal fat
      was found to be associated with lower levels of GLUT4 in all adipose regions
      investigated.

PMID- 9165230
TI  - Reversibility of insulin resistance in obese diabetic patients: role of plasma
      lipids.
AB  - The aim of the present study was to measure whole body glucose uptake (M) and
      oxidation rate by euglycaemic hyperinsulinaemic clamp and indirect calorimetry in
      7 morbidly obese subjects (BMI > 40 kg/m2) at three time points: before bilio
      pancreatic diversion (BPD) surgery (Ob); 3 months after surgery POI; and after
      reaching stable body weight, at least 2 years after surgery POII. A group of 7
      control subjects (C), matched groupwise for sex, age and BMI with POII patients,
      was also studied. The M value at POI was significantly higher than at Ob (49.12
      +/- 8.57 vs 18.14 +/- 8.57 mumol.kg-1.min-1). No statistical difference was
      observed between the POII and C groups. Similarly, glucose oxidation rate was
      significantly increased at POI with respect to Ob (24.2 +/- 7.23 vs 9.42 +/- 3.91
      mumol.kg-1.min-1) and was not significantly different between POII and C. Basal
      levels of non-esterified fatty acids (NEFA) decreased significantly both from Ob
      to POI and from POI to POII (1517.1 +/- 223.9 vs 1039.6 +/- 283.4 vs 616.0 +/-
      77.6 mumol.1(-1). The same applied to basal plasma triglycerides (2.07 +/- 0.77
      vs 1.36 +/- 0.49 vs 0.80 +/- 0.19 g.1(-1). Weight decreased mainly in the late
      postoperative period (POI to POII 124.28 +/- 11.22 to 69.71 +/- 11.78, 83% of
      total decrement), rather than in the early postoperative period (Ob to POI 135.25
      +/- 14.99 to 124.28 +/- 11.22 kg, 17% of total decrement). We also report the
      clinical case of a young woman of normal weight, who underwent BPD for
      chylomicronaemia (secondary to familial lipoprotein lipase deficiency), whose M
      value, plasma insulin and blood glucose levels were normalized upon normalization
      of serum NEFA and triglyceride levels as determined by the therapeutic lipid
      malabsorption. In conclusion, in obese diabetic patients lipid malabsorption
      induced by BPD causes a definite enhancement of insulin sensitivity and glucose
      tolerance. This improvement in metabolism is noticeable before the surgery has
      major effects on body weight. These observations suggest that lowered plasma
      lipids, rather than weight loss per se, are the cause of the reversibility of
      insulin resistance.

PMID- 9165231
TI  - Leptin stimulates glucose transport and glycogen synthesis in C2C12 myotubes:
      evidence for a P13-kinase mediated effect.
AB  - It was recently shown that leptin impairs insulin signalling, i.e. insulin
      receptor autophosphorylation and insulin-receptor substrate (IRS)-1
      phosphorylation in rat-1 fibroblasts, NIH3T3 cells and HepG2 cells. To evaluate
      whether leptin might impair the effects of insulin in muscle tissue we studied
      the interaction of insulin and leptin in a muscle cell system, i.e. C2C12
      myotubes. Preincubation of C2C12 cells with leptin (1-500 ng/ml) did not
      significantly affect insulin stimulated glucose transport and glycogen synthesis
      (1.8 to 2 fold stimulation); however, leptin by itself (1 ng/ml) was able to
      mimic approximately 80-90% of the insulin effect on glucose transport and
      glycogen synthesis. Both glucose transport as well as glycogen synthesis were
      inhibited by the phosphatidylinositol-3 (PI3)-kinase inhibitor wortmannin and the
      protein kinase C inhibitor H7 while no effect was observed with the S6-kinase
      inhibitor rapamycin. We determined whether the effect of leptin occurs through
      activation of IRS-1 and PI3-kinase. Leptin did not stimulate PI3-kinase activity
      in IRS-1 immunoprecipitates; however, PI3-kinase activation could be demonstrated
      in p85 alpha immunoprecipitates (3.04 +/- 1.5 fold of basal). In summary the data
      provide the first evidence for a positive crosstalk between the signalling chain
      of the insulin receptor and the leptin receptor. Leptin mimics in C2C12 myotubes
      insulin effects on glucose transport and glycogen synthesis most likely through
      activation of PI3-kinase. This effect of leptin occurs independently of IRS-1
      activation in C2C12 cells.

PMID- 9165232
TI  - High glucose enhances the gene expression of interleukin-8 in human endothelial
      cells, but not in smooth muscle cells: possible role of interleukin-8 in diabetic
      macroangiopathy.
AB  - We examined the effect of high glucose concentrations on the production of
      interleukin(IL)-8, which seems to be important for the development of
      atherosclerosis, in cultured human aortic endothelial cells (AoEC) and smooth
      muscle cells (AoSMC). After incubating these cells with various concentrations of
      glucose for 2 days or 7 days, the IL-8 concentration in cell lysates was measured
      by enzyme-linked immunosorbent assay and the IL-8 mRNA expression was examined by
      Northern analysis. After 2 days' culture, 42.5 mmol/l glucose enhanced IL-8 mRNA
      expression in AoEC, but not in AoSMC, compared to 4 mmol/l glucose. After 7 days'
      culture, the IL-8 concentration in AoEC lysate and the expression of IL-8 mRNA
      were significantly increased by 20.5 mmol/l glucose, or 42.5 mmol/l glucose
      compared to 4 mmol/l glucose. On the other hand, the IL-8 concentration in AoSMC
      lysate was not affected by any glucose concentration and the expression of IL-8
      mRNA in AoSMC was diminished by high glucose. These results suggest that the
      chemotactic gradient by IL-8 is established between arterial intima and media in
      response to high glucose levels in diabetic patients, and that it may be one of
      the key factors for SMC migration to the intima leading to diabetic
      macroangiopathy.

PMID- 9165233
TI  - From plant to patient: an ethnomedical approach to the identification of new
      drugs for the treatment of NIDDM.

PMID- 9165250
TI  - Duhamel operation 40 years after: a multicentric study.
AB  - The authors present the results of an international retrospective study
      evaluating the present situation in using Duhamel's technique or its
      modifications in the treatment of Hirschsprung's disease on the basis a series of
      2430 patients. After evaluation of all important criteria and discussion with
      data from the literature it is concluded that the techniques is simple, fast,
      less shocking, logical, reliable, respecting the rectal anatomy and physiology,
      ingenious in its principle, without serious complications. The rectum is
      preserved in place with all its vascular drainage and innervation. This technique
      can be performed by every sufficiently experienced surgeon.

PMID- 9165251
TI  - Results of a modified Duhamel Operation for Hirschsprung's disease using the GIA
      stapler.
AB  - Thirty-six patients with Hirschsprung's disease underwent surgery using modified
      Duhamel operation with the GIA (gastrointestinal autosuture) stapler over a 12
      year period at our institution. We now present our experience from the
      perspective of postoperative complications and anorectal function. Postoperative
      complications included minimal anal bleeding due to the GIA stapler in 2
      patients, and mild enterocolitis in 6 patients. Severe complications such as
      anastomotic leakage or stricture were not observed in our series. Overall,
      postoperative anorectal function was good in patients without Down's syndrome or
      cerebral palsy. Follow-up of our patients showed that a good quality of life was
      achieved during childhood. We conclude, therefore, that the modified Duhamel
      operation, with the use of the GIA stapler, is a safe and easy procedure for
      correction of Hirschsprung's disease.

PMID- 9165252
TI  - Is fetal thoracic compression really the underlying mechanism of lung hypoplasia
      in oligohydramnios? An experimental study in a rabbit model.
AB  - Compression of the fetal thorax by the uterine wall is one of the theories
      proposed to explain the mechanism of lung hypoplasia in association with
      oligohydramnios. However, the reduction in the intrathoracic space and the
      evidence of compression on the fetal thorax have not been demonstrated in detail.
      Therefore an experimental study was planned to determine the effects of
      oligohydramnios on available intrathoracic space and lung volume in the rabbit
      fetus. Amniotic fluid was shunted into the peritoneal cavity between 23 and 31
      days of gestation. Intrathoracic space and lung volumes (TV and LV), and lung and
      body weight (LW and BW) values were measured in our study and control fetuses at
      term. Lung weight/body weight, lung volume/thorax volume, thorax volume/body
      weight ratios were calculated and the values of the fetuses with shunting and
      controls were compared. The difference between TV/BW ratios was not significant.
      LW/BW and LV/TV ratios were significantly reduced in experimental fetuses
      compared to the controls. Chronic drainage of amniotic fluid into the peritoneal
      cavity resulted in reduced LW/BW and LV/TV ratio, but did not effect TV/BW ratio.
      The low LV/TV ratio in the fetuses with shunting despite similar TV/BW ratio
      suggested that the diaphragm had been elevated. This is also an explanation for
      the observation of reduced chest circumference and chest circumference/abdominal
      circumference ratio in prolonged premature rupture of the membranes in vivo. The
      developing fetal lungs would undergo not only transthoracic but also trans
      abdomino-diaphragmatic compression. However, it is unlikely in the tubular shaped
      rabbit uterus. In oligohydramnios amniotic fluid dynamics or physical
      characteristics with its contents should be disturbed. A previous experimental
      study with herniation of the amniotic sac causing lung hypoplasia through reduced
      intraamniotic pressure without oligohydramnios also questioned the role of fetal
      compression. Although fetal lung development was significantly impaired, the
      thoracic cage was not affected by amniono-peritoneal shunting. Therefore, we
      suggest that lung hypoplasia resulted from another mechanism rather than thoracic
      compression.

PMID- 9165253
TI  - A series of 17 cases of congenital cystic adenomatoid malformation of the lung:
      management and outcome.
AB  - During a 5-year-period, 17 cases of congenital adenomatoid malformation of the
      lung were observed in the Department of Pediatric Surgery of Bologna University
      S. Orsola-Malpighi Hospital; 16 cases were diagnosed in utero by ultra-sound. 13
      patients had prenatal diagnosis between 21 and 23 weeks of gestation; 2 cases
      were diagnosed at 25 weeks and another one at 26 weeks. The other case came from
      another hospital, and the diagnosis was accidentally detected postnatally. In 3
      cases the parents decided to terminate the pregnancy 3 cases had spontaneous
      improvement during the last weeks of gestation, and were perfectly normal at
      birth. One case was lost to follow-up; all remaining patients underwent
      resection. Among these patients only one was a nonsurvivor, while 9 have
      completely recovered. However, one patient developed persistent pulmonary
      hypertension, which could successfully be treated with drugs, another underwent
      laser treatment for laryngeal stenosis due to intubation. A special
      epidemiological information: 13 out 17 cases (76.5%) were female.

PMID- 9165254
TI  - Inhaled nitric oxide increases survival rates in newborn rats with congenital
      diaphragmatic hernia.
AB  - The high mortality of newborn infants with congenital diaphragmatic hernia (CDH)
      can be partly attributed to pulmonary hypertension causing extrapulmonary right
      to-left shunting with subsequent severe hypoxemia. Inhaled nitric oxide (NO) may
      reduce elevated pulmonary artery pressure and has been successfully improve
      arterial oxygenation in some newborns with CDH. However, it is not clear whether
      inhaled NO will actually improve survival of newborns with CDH. We therefore
      investigated the effect of inhaled NO on the survival rate of newborn rats with
      CDH following intrauterine exposure to nitrofen. A total of 151 newborn rats (9
      litters) were exposed to nitrofen on day 11 of pregnancy, After spontaneous
      delivery, 63 newborn rats (4 litters) were allowed to spontaneously breathe air
      containing NO (80 parts per million), while 88 newborn rats (5 litters) were
      given air without NO. Survival was checked 15 min after birth and then hourly
      until the animals were sacrificed at 24 h of age to verify the absence or
      presence of CDH. The 2 groups of newborn rats breathing air with or without NO
      did not differ significantly with respect to the presence or size of CDH. Twenty
      four of 63 (38%) newborn rats breathing air with NO survived for 24 h, compared
      to 12 of 88 (14%) rats breathing air alone (p < 0.01). Of newborn rats that were
      actually found to have CDH (n = 113), 8 of 42 (19%) animals breathing air with NO
      survived for 24 h, compared to 2 of 71 (2.8%) animals breathing air alone (p <
      0.01). In animals with CDH confirmed by autopsy, the median survival time was
      significantly longer with NO (p < 0.001) ( 2 h, interquartile range 2h-15h), than
      those breathing or without NO (median/interquartile range 15 min). We conclude
      that in the nitrofen rat CDH model, significantly improved survival rates occur
      with inhaled NO as a sole intervention. The combined impact of inhaled NO and
      mechanical ventilation remains to be determined.

PMID- 9165255
TI  - Prognostic factors of the postoperative vomiting in case of hypertrophic pyloric
      stenosis.
AB  - From January 1986 to February 1994, 198 children were operated on for
      hypertrophic pyloric stenosis (HPS). Postoperative follow-up have been carried
      out in 194 cases. The children were divided into two groups: group A (n = 134;
      69.1%): without any postoperative diet troubles (n = 52) or simple regurgitations
      (n = 82), and group B (n = 60; 30.9%) presenting more significant vomiting
      requiring medical treatment (n = 52) or a prolongation of parental nutrition (n =
      8). A retrospective study of the different factors which can possibly explain
      this postoperative vomiting was carried out. The criteria having an influence
      are: the age (44.5 days in group A; 35.7 days in group B; (p < 0.001) the weight
      at the time of the operation (3921) g in group A; 3647 in group B; p = 0.01) the
      thickness of the pylorus at the pre-operative ultrasound scan (5.2 mm in group A;
      47 in group B; p < 0.015). The other studied criteria (prematurity, birth weight,
      delay in diagnosis, weight loss, hydroelectrolytic abnormalities, surgical
      approach way-subcostal or umbilical-, surgical difficulties and operation
      duration) are not statistically significant. The young age (and therefore the low
      weight) at the time of the pyloromyotomy can easily explain the post-operative
      vomiting through the physiological immaturity of the lower sphincter of the
      esophagus. It is more paradoxical to note that these difficulties are all the
      more frequent because the pyloric tumor is less thick at the ultrasound scan. But
      this criterion is also directly related to the child's age (average thickness of
      4.5 mm before the age of one month and 5.8 mm after the age of two months; p <
      0.0001). These data suggest the importance of systematic medical treatment to
      prevent postoperative vomiting in high-risk children, in order to decrease
      hospital stay (4.14 days in group A; 5.20 days in group B; p < 0.0001).

PMID- 9165256
TI  - Three-dimensional endosonography of the pelvic floor: an additional diagnostic
      tool in surgery for continence problems in children.
AB  - Three-dimensional endorectal sonography with a specially developed system is able
      to produce an image of the entire pelvic floor including the sphincter muscles
      and the rectal wall even in small children. This special system is based on
      conventional endorectal ultrasound and allows recording of a controlled
      withdrawal of the axially rotating transducer, creating an image sequence
      resembling that of a spiral CT-scan; this sequence is digitized off-line and
      evaluated in a three-dimensional form by a workstation computer. This evaluation
      has several advantages compared with conventional examination, for example, the
      complete recording of organs with the possibility of volumetry, construction of
      arbitrary sections, volume-rendering procedures and the interactive segmentation
      of organ borders and their three-dimensional visualization. Based on images from
      this 3D endorectal sonography, the normal anatomy of the pelvic floor that is
      visible using ultrasound is described, followed by some pathological findings
      concerning continence surgery. Finally we discuss the advantages and restrictions
      compared to other examination procedures and the possibilities of technical
      development.

PMID- 9165257
TI  - Isolate abdominal bronchogenic cyst: a case report.
AB  - Isolated abdominal bronchogenic cysts are rare abnormalities. They are usually
      asymptomatic unless secondarily infected or large enough to cause compression of
      other vital structures. The authors report on a 20-month-old girl who had an
      abdominal bronchogenic cyst and presented with a history of recurrent urinary
      tract infections. The evaluation and treatment of this patient is presented as
      well as a review of the ten previously reported cases. A literature review showed
      only four cases in the pediatric age group. Excision is recommended to establish
      diagnosis and alleviate any symptoms. Abdominal bronchogenic cysts should be
      considered in the differential diagnosis of retroperitoneal masses.

PMID- 9165258
TI  - Acute gastric volvulus and congenital posterolateral diaphragmatic hernia.
AB  - Acute gastric volvulus in infancy is a rare disorder and a surgical emergency.
      Prompt clinical suspicion and radiological assessment are essential for this life
      threatening condition. We report a 3-month-old female case, admitted for an
      initial suspicion of an intestinal obstruction. She presented unproductive
      retching, respiratory distress, epigastric distension and lethargy. It was not
      possible to introduce a naso-gastric tube. A radiological contrast study showed
      an occluded cardio-esophageal junction without passage of barium, two gastric
      fluid levels and a horizontally positioned stomach occupying the inferior portion
      of the left hemithorax, suggesting a left diaphragmatic hernia. Laparotomy
      revealed an acute mesenterico-axial gastric volvulus with a left posterolateral
      diaphragmatic hernia. The stomach volvulus was untwisted, the diaphragmatic
      defect was repaired after reduction of the herniated contents and no gastropexy
      was done. At 3 and 6-months follow-up examination the infant was asymptomatic and
      thriving.

PMID- 9165259
TI  - Pancreatitis due to cystic duodenal duplication in a 12-year-old child.
AB  - Duodenal duplications are rare congenital anomalies which can present with
      pancreatitis. A precise preoperative diagnosis is rarely possible. We present a
      12-year-old girl with relapsing pancreatitis in whom the diagnostic survey was
      initially inconclusive. Two years later abdominal ultrasound revealed a cyst near
      the head of pancreas. At laparotomy a cysto-duodenostomy was performed. The
      histology of the cyst wall was diagnostic.

PMID- 9165260
TI  - Retroperitoneal lymphangiomyoma in an infant.
AB  - Lymphangiomyomatosis (LAM) is a benign tumor-like lesion of lymphatic vessels
      with unknown etiology. 80 cases of LAM are presently described. So far, it
      appears that only women in their reproductive years seem to be affected. Here, we
      describe the first LAM in an 11-months-old infant with a presumably local form of
      LAM. This leads us to consider the possibility that this tumor-like lesion may
      originate from a hamartomateous malformation. The diagnosis is based on pre
      operative sonography and CT, as well as on histological and immunohistochemical
      examination of the tumor.

PMID- 9165261
TI  - Nephrogenic adenoma in children. Case report and review of literature.
AB  - Nephrogenic adenoma in children is an extremely rare kind of tumor (22 cases have
      been described to date). We report and discuss here the case of a 7-year-old
      girl, taking into account the findings described in medical literature. In
      contrast to nephrogenic adenomas in adults, who present with this tumor in the
      entire ureteral tract, it has been observed exclusively in the bladder in
      children so far. The most frequent predisposing factors for the development of
      this tumor are extensive surgical injury such as ureter reimplantation or long
      term stimuli on the urothelium caused by a foreign body. Diagnosis primarily
      includes sonography of the urinary tract and cystoscopy. Transurethral resection
      is regarded as the treatment of choice. Owing to the frequency of persistence,
      control cystoscopies after primary therapy are necessary.

PMID- 9165262
TI  - Torsion of spermatocele and aplasia of the vas deferens. A case report.
AB  - Torsion of a spermatocele combined with aplasia of the vas deferens is described.
      The purpose of this case report is that this rare condition should not be omitted
      from the differential diagnosis of the acute scrotum in childhood. The authors
      also support that the term "spermatocele" could be used in the non semen
      producing age of childhood, based upon the non age-dependent pathologic criteria.

PMID- 9165263
TI  - Fetus in fetu and cystic rectal duplication in a newborn.
AB  - A case of sacrococcygeal teratoma is presented with characteristics of fetus in
      fetu in association with rectal duplication and bilateral cryptorchidism.

PMID- 9165264
TI  - Congenital lumbar hernia associated with the lumbocostovertebral syndrome: two
      cases.
AB  - Congenital hernias in the lumbar region are very uncommon. Two cases with
      congenital lumbar hernia associated with the lumbocostovertebral syndrome are
      presented. The first case of a 14-month-old girl presented with the type of a
      superior lumbar triangle hernia. The second case was a 2-year-old girl presenting
      with diffuse lumbar hernia. The anatomy, embryology and treatment of this
      congenital abnormality are discussed.

PMID- 9165265
TI  - Gm and Km allotypes and typhoid fever.
AB  - Gm and Km allotypes of immunoglobulins were determined in children with typhoid
      fever (Cases), in children without infectious diseases (Con-1), and in children
      with fever but no Salmonella in their blood or bone marrow (Con-2). Children were
      sampled from the urban population of Santiago; and they belonged to the low and
      low-middle socioeconomic strata. Cases had a higher frequency of [f;(-);b1,b3 or
      3;(-);5,13] G1m, G2m, G3m haplotype than Con-1 and Con-2. Con-1 and Con-2 did not
      differ in their Gm haplotype or Km allele frequencies, but they differed in
      phenotype distribution. Con-1 deviated from Hardy-Weinberg equilibrium for Km due
      to a lack of Km 1-1 homozygotes. The relationship among these results, the ethnic
      origin of Chileans, and the differential susceptibility to typhoid fever are
      discussed.

PMID- 9165266
TI  - GM allotypes and IgG subclass concentrations in blacks.
AB  - IgG subclass concentrations were measured in 352 black Americans. Sera were also
      typed for nine GM allotypes. Serum concentrations of IgG1, IgG3, and IgG4 varied,
      to different degrees, according to GM phenotypes. The concentration of IgG1 was
      lower in subjects with GM 1,3,17 5,6,13 compared to those who lacked this
      phenotype. Elevated levels of IgG3 and IgG4 were associated with GM 1,17 5,6,13
      and GM 1,3,17 23 5,13, respectively. Subjects with GM 1,17 5,13,21 had lower
      levels of IgG3 than individuals with other phenotypes. IgG2 levels were not
      associated with any of the GM phenotypes. To our knowledge, this represents the
      first report of an association between GM allotypes and IgG subclasses in blacks.

PMID- 9165267
TI  - Analysis of the VH3 repertoire among genetically disparate individuals.
AB  - It has been shown that a conserved but highly biased subset of the germline VH
      complement is utilized in the peripheral VH repertoire of Caucasians. To
      distinguish between VH-autonomous effects and background genetic effects, we have
      now assessed the incidence of rearrangement of eight VH3 gene segments in
      preimmune CD19+IgD+B cells from genetically disparate subjects of diverse ethnic
      backgrounds. Results indicate that the set of gene segments utilized for
      rearrangements by these subjects is similar, and predominantly reflects the bias
      previously observed in Caucasians. The preimmune repertoire of each subject is
      dominated by two or three gene segments, with a predominant expression of V3-23
      in all the subjects. Variation in the use of individual gene segments, including
      V3-23, was observed among the subjects. These results indicate that the processes
      that favor the preferential use of particular genes is largely independent of
      genes outside the VH locus. The minor variation in utilization of VH segments,
      however, is probably influenced by the genetic background of the individual.

PMID- 9165268
TI  - Serological and molecular identification of an HLA-B8 variant, HLA-B8Jon
      (B*0802).
AB  - The serological and molecular characteristics of the first HLA-B8 variant
      (B8Jon), located on a haplotype bearing HLA-A1, -B8Jon, -Cw*07, DRB1*0301,
      DQA1*05, DQB1*0201, BfS, C4AQ0, C4B1 and the microsatellite alleles D6S265-3, 258
      11, 105-8, 299-1 and 202-2 are identified and described. This new HLA-B antigen
      was distinguished from the usual B8 by its lack of reactivity with Bw6 and most
      Bw4 antisera, together with its failure to react with most antisera cross
      reactive with HLA-B8. B8Jon gives a 'weaker' response than HLA-B8 in titration
      studies with B8 antisera. It cannot be differentiated from the usual B8 by one
      dimensional iso-electric focusing. Time course studies, absorption analyses and
      serological tests on 17 Bw4 antibodies suggest that B8Jon possesses an unusually
      'weak' Bw4 epitope. Studies on the Bw4 sequence motif by PCR, using sequence
      specific primers, indicate that B8Jon has a Bw4 sequence in common with other HLA
      B alleles, including B*4402-B*4405, rather than the Bw6 motif found on the
      familiar HLA-B8 molecule.

PMID- 9165269
TI  - Homologues of murine Vh11 gene are conserved during evolution.
AB  - Since the murine Vh11 gene family shows 75% homology with group III VH gene
      families and is preferentially expressed in B-1 lymphocytes, we have analyzed if
      corresponding Vh11 genes existed across phylogenetically distant mammalian
      lineages. In a Southern blot, homologues of the murine Vh11 gene were detected in
      the genomic DNA from rats, pigs, sheep, cattle, horses, dogs and man. These
      observations suggest conservation of corresponding sequences of the Vh11 gene
      family during evolution, similar to group III VH genes, either because of strong
      selection pressures essential for species fitness and survival or molecular drive
      leading to these consequences.

PMID- 9165270
TI  - Temperature-dependent surface expression of the beta-2-integrin analogue of
      Candida albicans and its role in adhesion to the human endothelium.
AB  - Candida albicans has become one of the most important pathogens in intensive care
      units. Adherence of C. albicans to the vascular endothelium is believed to
      represent a critical step in the pathogenesis of disseminated candidiasis and may
      involve molecules analogous to human beta 2-integrins such as the complement
      receptor 3 (CR3) analogue of C. albicans (C.a.-CR3). Its expression was detected
      by a sensitive rosetting assay when Candida was present in its hyphal form but
      not in its yeast form, the latter being generally considered to be less
      pathogenic. However, the presence of hyphae alone was not sufficient: C.a.-CR3
      expression was found to be temperature-dependent for 4 (out of 10) clinical
      isolates. Two rosetted better after growth at 30 degrees C, the other 2 after
      growth at 37 degrees C. This temperature dependence was most pronounced for 1
      laboratory strain: C.a.-CR3 expression was best at 30 degrees C and markedly
      decreased with increasing temperatures. At 37 degrees C no rosettes were detected
      at all. Modifications of the culture conditions (e.g. agitation, pH) exerted a
      marked influence on the morphology of this strain but always allowed rosette
      formation once hyphae were formed at 30 degrees C. However, none of these
      modifications was able to induce rosettes at 37 degrees C. Adhesion of C.
      albicans isolates to an endothelial cell line was also temperature-dependent but
      not strongly correlated with C.a.-CR3 expression. Most strains exhibited a better
      adherence when grown at 30 degrees C. This finding may be of importance for
      exogenous infections, with Candida spp. invading the body from the outside, where
      the temperature is usually lower than the physiological body temperature.

PMID- 9165271
TI  - Detection of heterozygous C8 beta deficiency by PCR in a healthy Italian
      population.
AB  - In Italy a rather high number of homozygotes with late complement component
      defects has been found among patients with meningococcal disease. It seems that
      clinical manifestations of meningococcal disease are less severe in patients with
      complement deficiency than in normal individuals. This situation could even be
      more evident in the heterozygous carriers for whom a selective advantage is
      discussed. In this study we have screened a cohort of 527 Italian blood donors
      from western Sicily for the presence of C8B mutated allele. Heterozygotes for C8
      beta deficiency were identified using a specific PCR assay to detect a C-->T
      transition in exon 9 of the C8B gene. This mutation represents the most frequent
      genetic mechanism for C8 beta deficiency in Caucasians. A rapid PCR screening
      test was performed on DNA extracted from pooled blood samples of up to 8
      individuals. A single male individual with heterozygous C8 beta deficiency was
      detected. In the family studies it was shown that his two brothers and the mother
      were heterozygous carriers too. Functional activity of the classical and
      alternative complement pathways were normal. No neisserial infections or
      inflammatory diseases were found in the family history. It was shown that the
      allele-specific PCR is a sensitive and rapid method to examine large numbers of
      DNA samples. It permitted to assess the real prevalence of the C8B mutated null
      allele in the general population free of ascertainment bias.

PMID- 9165272
TI  - Autoantibodies to T-cell receptor beta chains in human heart transplantation:
      epitope and spectrotype analyses and kinetics of response.
AB  - Autoantibodies against T-cell receptors have been found in two alloimmunization
      situations in humans: renal transplantation and pregnancy. We carried out
      longitudinal studies of human heart transplant recipients monitoring their
      autoantibody production to a recombinant single chain T-cell receptor V alpha/V
      beta construct, a set of nested, overlapping peptides duplicating the complete
      covalent structure of an individual T-cell receptor beta chain and a set of
      peptides duplicating the first complementarity determining segments of 24
      distinct human V beta gene products in order to define the time course, epitope
      specificity and recognition heterogeneity of the response. Autoantibodies against
      intact and peptide-defined V beta and C beta determinants were generated
      following human heart allotransplantation. The responses generally show an
      increase following transplantation that subsequently decreases with time, a
      result which is consistent with a single immunization. However, some patients
      showed elevated responses as long as 12 months following the transplant.
      Autoantibody anti-CDR1 spectrotype analyses detected individual differences among
      patients, but 5 of 8 patients characterized in detail showed elevated IgG binding
      to CDR1 peptide epitopes of V beta 6.1, 21.1 and 22.1 gene products.
      Autoantibodies to CDR1 epitopes of V beta 7.1 and 8.1 were high pretransplant and
      remained high, although the relative increases with respect to the pretransplant
      values were not as impressive as those for the above CDR1 epitopes and others
      usually present in low quantity, e.g. anti-V beta 2.1, 3.1 and 24.1. Although
      there was great disparity between the MHC haplotypes of donors and recipients,
      and individual differences among patients, the degree of restriction in the
      autoantibody response was surprising and suggests a common step in recognition
      and regulation of the response to allografts.

PMID- 9165273
TI  - Human thymic epithelial cells present superantigens to T-cell lines and
      thymocytes.
AB  - It is generally accepted that thymic epithelial cells (TEC) act as accessory
      cells in positive selection of pre-T cells. However, our knowledge of the antigen
      presentation and accessory cell function to human TEC is limited. Here we present
      results obtained by the use of serum-free cultured human TEC, showing that IFN
      gamma-treated TEC are able to support T-cell-mediated responses to the bacterial
      superantigens (Sag) SEA and SEB, even at very low Sag concentrations. T-cell
      responses to TEC-presented Sags were dependent on the presence of the adhesion
      molecules ICAM-1, ICAM-2, LFA-1, and LFA-3, but not on CD4 and CD8 molecules.
      There is a low but significant expression of B7 molecules on human TEC, and
      treatment of TEC with anti-B7.1 and anti-B7.2 antibodies before Sag pulsing leads
      to decreased Sag responses, indicating a significant importance of B7 molecules
      on TEC. Both CD4+ T-cell lines and CD4+ as well as CD8+ subpopulations of
      thymocytes showed significant responses, whereas nonseparated thymocytes, CD4+8+,
      and CD4-CD8- thymocytes did not respond or showed very low responses. In
      conclusion, the present results demonstrate that cultured human TEC are able to
      present Sag to thymocytes.

PMID- 9165275
TI  - Identification of a polymorphism in the transmembrane domain of the protooncogene
      c-kit in healthy subjects.
AB  - c-Kit is the receptor for stem cell factor (SCF) and is found on hematopoietic
      stem cells, mast cells, melanocytes, and germ cells. Aggregation of c-Kit by SCF
      regulates cell proliferation, differentiation, and survival. In the process of
      examining c-Kit, a polymorphism in the transmembrane domain of the protooncogene
      c-Kit was identified. This polymorphism consisted of an A-to-C transversion at
      nucleotide (nt) 1642, and was deduced to substitute leucine for methionine at
      codon 541. The frequency of the allele with 'C' at nt 1642 was 0.09 in 64
      unrelated subjects. Analysis of a two-generation family with the polymorphism
      suggested that this polymorphism did not result in disease. This is the first
      report of a polymorphism in the transmembrane domain of c-Kit, and may be of
      value in understanding and following the function of c-Kit in normal subjects and
      in those with other abnormalities of c-Kit.

PMID- 9165274
TI  - Molecular genetic analysis of HLA-DRB, -DQA, and -DQB polymorphisms in Hungarians
      and distribution of the DRB1*03 allele in adults and newborns.
AB  - We describe here the genetic variability of HLA-DRB1, -DQA, and -DQB in 140
      healthy individuals from Hungary, including 95 randomly selected adults and 45
      newborns. Allele and haplotype frequencies as well as linkage disequilibria were
      calculated. It was found that HLA-DRB1*11, -DQA1*0501, and -DQB1*0301 predominate
      in Hungarians. This information may be helpful in the future for HLA and disease
      association studies. Simultaneously, we observed that the frequency of the
      DRB1*03 allele differs between adults and newborns. Since it is well known that
      bearers of HLA-DR3 (and/or B8) antigens may display significant changes in immune
      parameters, the lower frequency in adults indicates that children with the DR3
      antigen are predisposed to immune diseases in adulthood.

PMID- 9165276
TI  - Using PBL as a creative teaching tool.

PMID- 9165277
TI  - Nursing homes can be a resource for teaching dermatology.

PMID- 9165278
TI  - Dilemmas in family practice education. How to handle inpatients.

PMID- 9165279
TI  - Advice for community physicians about to become teachers of residents.

PMID- 9165280
TI  - Caring for the health of populations: will family practice residents be prepared
      to meet the challenge?

PMID- 9165281
TI  - Pap smear adequacy: the role of clinician experience.
AB  - BACKGROUND AND OBJECTIVES: The Papanicolaou (Pap) smear is a widely accepted tool
      for the detection and prevention of cervical cancer. Under the Bethesda Scoring
      System, the key internal control for adequacy of the smear is the presence of
      endocervical cells. Over the past several decades, much effort has been
      undertaken to maximize the adequacy of this acquisition. The present study
      determined if Pap smear sample adequacy is related to clinician experience.
      METHODS: This study includes a retrospective analysis of 1,356 Pap smears
      acquired between January 1992 and January 1995. The procedures were performed by
      family practice residents and faculty physicians. Cervical smears were obtained
      with a combination of a cytobrush and an Ayre spatula and were placed on two
      slides. Adequacy was subsequently determined by a cytotechnologist. Chi-square
      analysis was used to determine if the adequacy rates for faculty and for PGY-1,
      PGY-2, and PGY-3 residents were significantly different. RESULTS: The adequacy
      rates for PGY-1, PGY-2, PGY-3 residents and faculty physicians were 80%, 89%,
      89%, and 93%, respectively. The adequacy rates for the first-year residents were
      significantly different from that of all other studied groups. CONCLUSIONS: This
      study demonstrates the relationship between clinician experience and the ability
      to perform an adequate Pap smear. Considering the cost and potential medical risk
      of an inadequate Pap smear, family practice residency programs should increase
      the degree of PGY-1 education and experience in performing Pap smears.

PMID- 9165282
TI  - Family physician perception of economic incentives for the provision of office
      procedures.
AB  - BACKGROUND AND OBJECTIVES: The influence of capitation versus fee-for-service
      reimbursement for services provided by primary care physicians is an important
      topic as capitation becomes increasingly prevalent. This study ascertained
      whether family physicians perceive an economic incentive to perform flexible
      sigmoidoscopy, colposcopy, and vasectomy under capitated versus fee-for-service
      payment structures. METHODS: In May 1995, questionnaires were mailed to 592
      randomly selected physician "diplomates" of the American Board of Family Practice
      in California, Florida, Texas, Virginia, and Minnesota. Nonrespondents received
      an additional mailing in July 1995. RESULTS: The return rate was 62%. Of 336
      responses: 1) 177 (52%) provide flexible sigmoidoscopy; 68 (20%) think capitation
      and 173 (51%) think fee for service provide sufficient reimbursement to make this
      procedure profitable. 2) 69 (20%) provide colposcopy; 50 (16%) think capitation
      and 99 (30%) think fee for service provide sufficient reimbursement to make this
      procedure profitable. 3) 91 (27%) provide flexible sigmoidoscopy; 36 (11%) think
      capitation and 84 (25%) think fee for service provide sufficient reimbursement to
      make this procedure profitable. CONCLUSIONS: A significant number of family
      physicians provide these three procedures in their offices. Most physicians view
      fee-for-service payment as providing an economic incentive to provide these
      procedures. Capitation was less frequently perceived as providing sufficient
      reimbursement to make the provision of these procedures profitable.

PMID- 9165283
TI  - Practice patterns among primary care physicians in benign prostatic hyperplasia
      and prostate cancer.
AB  - BACKGROUND AND OBJECTIVES: Although patients with prostate disorders are
      frequently referred to urologists for diagnosis and management, primary care
      physicians (PCPs) are beginning to take a more active role. However, there is
      concern that PCPs are not optimally educated in the diagnosis and management of
      these disorders. This survey determined PCP practice patterns in evaluating and
      treating benign prostatic hyperplasia (BPH) and screening for prostate cancer.
      METHODS: A 10-question survey was completed by 344 physicians attending various
      scientific meetings in 1995. RESULTS: Most PCPs (89%) indicated that up to 30% of
      their patients have symptomatic BPH, and a significant proportion of these are
      treated initially by the PCP. Although 61% of PCPs are aware of the American
      Urological Association (AUA) symptom score and its recommended role in clinical
      practice guidelines, only 38% currently use it. Indications for using the AUA
      score include men with BPH symptoms (80%), men > 50 years (55%), and men with an
      abnormal digital rectal examination (DRE) (42%). The most popular BPH therapies
      are long-acting alpha blockers and watchful waiting. DRE is performed routinely
      by 84% of PCPs in men > 50 years, and annual serum prostate-specific antigen is
      routinely requested by 69% of PCPs. CONCLUSIONS: Although PCPs play an increasing
      role in the diagnosis and management of prostate disorders, they are not taking
      full advantage of published clinical practice guidelines.

PMID- 9165284
TI  - Let's party tonight: drinking patterns and breath alcohol values at high school
      parties.
AB  - BACKGROUND AND OBJECTIVES: This study sought to determine whether the number of
      alcohol-containing beverages consumed by adolescents attending a "typical" high
      school weekend party was planned or spontaneous. A second objective was to
      understand the role of the designated driver and whether he or she honored a
      pledge of sobriety. METHODS: A printed, anonymous survey with signed informed
      consent was distributed to 52 high school students from three different suburban
      high schools during three weekend high school parties. In addition, subjects
      underwent breath alcohol testing using the Intoximeter breath alcohol instrument.
      Salivary alcohol measurements were also obtained using Alco-Screen. Levels were
      measured in volunteers on entry and exit from the party. RESULTS: Fifty-two
      students volunteered to participate in the survey. Eleven participants
      volunteered to be designated drivers, nine of whom did not drink alcohol at this
      party. By the end of each party, the 26 boys had consumed a mean of 10 drinks,
      and the 16 girls had consumed 4.1 drinks, almost exactly what they had predicted
      at the time of arrival. By departure time, 22 (54%) of the drinkers had a breath
      alcohol value of .10 g/dL or greater, while only three (7%), had alcohol values
      of .02 g/dL or less. Blackouts were common and had been experienced by 73% of all
      the students surveyed. Twenty-seven percent of those surveyed had been involved
      in some form of physical violence while drinking. Eleven percent of the female
      participants reported being sexually assaulted while they or their attacker were
      drunk. Most of the 42 drinkers believed that it was acceptable for designated
      drivers to drink at least two beers. Two intoxicated designated drivers were
      driven home by sober friends. CONCLUSIONS: High school students in this study
      knew before attending a party the quantity of beer they would consume. Survey
      participants believed that it is acceptable practice for designated drivers to
      drink alcohol at parties; 13% of those who intended to drive after these parties
      were intoxicated.

PMID- 9165285
TI  - Implementation of CAGE alcohol screening in a primary care practice.
AB  - BACKGROUND AND OBJECTIVES: Alcoholism is a common problem in primary care.
      Although the four-question CAGE screening tool was developed for use by primary
      care physicians, studies show that the questionnaire is still not widely used in
      clinical practice. This study tested the effectiveness of an intervention to
      increase physicians' use of the CAGE questions. METHODS: We reviewed medical
      records charts completed by 15 family practice residents for documented
      alcoholism screening, both before and after an educational intervention. The
      intervention included modification of examination forms to include the CAGE
      questions, as well as written feedback from faculty members regarding residents'
      documentation of alcohol screening. RESULTS: We reviewed a total of 170 pre- and
      227 post-intervention charts. Following educational intervention, documentation
      of quantity/frequency of alcohol beverage consumption increased from 26.5% to
      93%. The use of CAGE screening increased from 5.9% to 76.7%. For post
      intervention charts that documented using the four CAGE questions, 12.6% showed
      one or more positive responses. Of these charts, 27% documented physician
      intervention such as a warning or referral for treatment of alcohol-related
      problems. CONCLUSIONS: Our educational intervention was a successful way to
      improve physicians' use of CAGE questions to screen for alcoholism.

PMID- 9165286
TI  - Scheduled hand washing in an elementary school population.
AB  - BACKGROUND AND OBJECTIVES: Hand washing prevents communicable illness. We
      evaluated the effect of a mandatory, scheduled hand-washing program in elementary
      school children on absenteeism due to acute communicable illness. METHODS: The
      study was conducted at Trombley Elementary School in Grosse Pointe Park, Mich.
      The intervention group, approximately half of the school children (n = 143,
      including all grades 1-5), washed their hands a minimum of four scheduled times a
      day. The control group (n = 162) continued hand-washing practices as usual.
      RESULTS: Of the 37 school days examined, children in the hand-washing group were
      absent fewer days than the control group due to all acute communicable illness
      (relative risk = .75). There were less days of absence due to gastrointestinal
      symptoms (relative risk = .43). The difference in absence due to respiratory
      symptoms was not statistically significant. CONCLUSIONS: A scheduled hand-washing
      program will reduce acute communicable (gastrointestinal) illnesses in elementary
      school-age children.

PMID- 9165287
TI  - Assaults against general practitioners in Ireland.
AB  - BACKGROUND AND OBJECTIVES: Violence directed at general practitioners (GPs) is on
      the increase in urban areas of Ireland. However, little information has been
      available on the incidence, effects, or precipitants of this violence. This study
      documents the frequency of the problem in Ireland's capital city, Dublin.
      METHODS: A survey was sent to all 634 GPs in the Eastern Health Board region of
      Ireland. The survey asked each GP to report an incident of violence or aggression
      using standardized definitions and reporting forms. The survey also requested
      that participants provide information on their practice and its staff and
      setting. RESULTS: We collected information from 622 of 634 doctors (98%). The
      overall incidence of violence or aggression in the sample was 21%. Of the 131
      incidents reported, only 7% resulted in injury to the doctor; the remainder all
      involved verbal abuse and/or threats. The most frequent assailant characteristics
      identified were alcohol or opiate abuse. CONCLUSIONS: Violence and aggression
      against GPs are common. Several interventions are discussed.

PMID- 9165288
TI  - Sustained normotension in hypertensive patients withdrawn from medication for 1
      year.
AB  - BACKGROUND AND OBJECTIVES: Prior research indicates that up to 5% of hypertensive
      subjects can be successfully withdrawn from antihypertensive medications. This
      study determined if, in a family practice setting, greater than 5% of patients
      with mild essential hypertension could be withdrawn from their antihypertensive
      medication for more than 1 year and remain normotensive. METHODS: We enrolled 116
      randomly chosen volunteer patients. Of these, 96% were white, and 58% were
      female. The mean age was 57, and the mean history of hypertension was 10.1 years.
      RESULTS: A total of 81 subjects completed the study; 46.9% of those 81 remained
      normotensive for 1 year after stopping medication. Females tended to do better
      than males at withdrawing from antihypertensives (58% versus 33%). CONCLUSIONS:
      The proportion of patients who successfully withdrew from antihypertensive
      medication for 1 year and remained normotensive was significantly greater than
      expected. Further studies are needed to identify factors that predict which
      patients will remain normotensive without medication.

PMID- 9165289
TI  - The cost of outpatient training of residents in a community health center.
AB  - BACKGROUND: The system of paying for graduate medical education is undergoing
      reform. As financing changes, understanding the costs of training family practice
      residents in the outpatient setting will be critical. METHODS: A financial model
      was used to analyze retrospective data from an existing residency and community
      health center linkage in Utah. Data from 1994 were used to estimate fixed and
      variable costs and income associated with the training program. The net cost of
      training residents was determined, as well as the cost of replacing their
      services with staff physicians. RESULTS: This outpatient program generated an
      average of $1,933 per resident in annual revenues above expenses. If staff
      physicians replaced residents in providing the same services, the health center
      would have generated an additional $5,033 per resident in income. If precepting
      faculty were paid rather than volunteer, the program would cost $7,912 per
      resident per year. Under baseline assumptions, an educational supplement of $9.52
      per patient would be required for the residents to break even relative to staff
      physicians. CONCLUSIONS: Graduate medical education reform will need to include
      provisions for reimbursing host facilities for the increased cost of outpatient
      care provided by residents.

PMID- 9165290
TI  - Medical school culture and generalist education: perceptions of a medical school
      faculty.
AB  - BACKGROUND AND OBJECTIVES: As part of an initiative to promote the education of
      generalist physicians at the University of North Carolina, a series of meetings
      were held over a 12-month period between generalist senior faculty and faculty
      from a range of departments in the School of Medicine and other health
      professions schools. Through open discussion about generalist initiatives, we
      hoped to understand their issues, attitudes, and opinions regarding generalists
      and generalist education. The major themes arising from these dialogues were 1)
      uncertainty about the definition of the generalist physician, 2) beliefs about
      the poor clinical reputations of generalists, 3) lack of a scientific basis for
      generalist practice, and 4) beliefs that few new resources are needed to
      undertake and expand generalist education. We comment on the validity and
      possible reasons for these perceptions and suggest strategies that can enhance
      generalist culture in the medical school.

PMID- 9165291
TI  - Chronic inhibition of the high-affinity dopamine uptake system increases
      oxidative damage to proteins in the aged rat substantia nigra.
AB  - The effect of chronic treatment of aged rats with nomifensine has been studied in
      the rat nigrostriatal dopaminergic system. The rat substantia nigra suffers an
      oxidative damage during aging that results in both an increase in carbonyl groups
      of its total proteins and the oxidative inactivation of tyrosine hydroxylase (TH)
      enzyme, which are partially reversed by chronic treatment with deprenyl.
      Different mechanisms may account for this effect, including inhibition of the
      high-affinity dopamine uptake system. We treated aged rats chronically with
      nomifensine for 2 months and found some significant effects. Nomifensine
      treatment significantly increased TH enzyme amount in substantia nigra (39.2%),
      which was accompanied by a significant increase in TH enzyme activity (47.8%).
      However, these effects were not observed in the terminal field (striatum). As a
      further step we quantified the oxidative level of proteins by measuring the
      number of carbonyl groups coupled either to total proteins or specifically to TH
      enzyme. The proteins of aged rat substantia nigra showed a significant increase
      of carbonyl groups following nomifensine treatment. The number of carbonyl groups
      coupled to nigral TH enzyme also increased in the nomifensine-treated animals.
      However, this increase was lower than that found in the total homogenate
      proteins. All these results show that the oxidative damage produced during aging
      in tyrosine hydroxylase enzyme and total proteins is not reduced by nomifensine
      treatment. On the contrary, the nomifensine treatment increased the oxidative
      damage to proteins. These results suggest the capability of deprenyl to induce TH
      enzyme could be due to inhibition of the high-affinity dopamine uptake system,
      but its ability to protect against oxidative damage is not produced by this
      mechanism.

PMID- 9165292
TI  - Hydroxyl radical is the major causative factor in stress-induced gastric
      ulceration.
AB  - The role of the metal-catalyzed production of hydroxyl radicals (OH.) on gastric
      ulceration caused by restraint-cold stress in rat was studied. Stress causes a
      50% increase in the thiobarbituric acid reactive species (TBARS) as a measure of
      the lipid peroxidation, nearly 70% increase in protein oxidation as measured by
      its carbonyl content and about 40% decrease in the glutathione content of the
      fundic stomach, suggesting oxidative damage by stress. Stress also causes a time
      dependent increase in the mitochondrial superoxide dismutase activity and a
      decrease in the peroxidase activity, both of which correlate well with the
      increase in the severity of ulceration as measured by the ulcer index. Specific
      OH. scavengers such as benzoate or dimethylsulfoxide (DMSO) and the free radical
      trap such as alpha-phenyl N-tert-butyl nitrone (PBN) significantly inhibit
      gastric ulceration suggesting the role of OH. in this oxidative damage.
      Desferrioxamine (DFO), a nontoxic transition metal ion chelator, protects the
      mucosa against stress-ulceration dose dependently. Increased level of TBARS and
      the inactivation of gastric peroxidase are also prevented by DFO or by
      antioxidants such as glutathione or vitamin E, suggesting the critical role of
      metal ion and OH. in the oxidative damage. A metal-catalyzed OH. generating
      system constituted by Cu2+, H2O2 and ascorbate (reducing equivalent of O2-)
      causes inactivation of the purified gastric peroxidase in vitro, which can be
      effectively prevented by DFO. The stress-induced activation of the superoxide
      dismutase is completely blocked by pretreatment with alpha-amanitin indicating an
      increased synthesis of the enzyme by increased transcription of its m-RNA.
      Quantitative measurement indicates that stress causes a fivefold increase in the
      generation of OH., which correlates well with the increase in ulcer index with
      the progress of stress. The results indicate that the stress-induced gastric
      ulceration is a consequence of the oxidative damage of the gastric mucosa. This
      is caused by the OH. generated through the metal-catalyzed Haber-Weiss reaction
      between O2- and H2O2, the latter being formed by the stimulation of the
      superoxide dismutase and inactivation of the gastric peroxidase.

PMID- 9165293
TI  - Potentiation of ischemia-reperfusion liver injury by hyperthyroidism in the rat.
AB  - Parameters related to hepatic oxidative stress, cell injury, and liver histology
      were determined in control rats and in animals treated with 3,3',5
      triiodothyronine (T3), after in vitro perfusion under normoxic or ischemia
      reperfusion conditions. Thyroid calorigenesis was found concomitantly with higher
      rates of hepatic O2 consumption and thiobarbituric acid reactive substances
      (TBARS) formation, glutathione (GSH) depletion, enhanced TBARS/GSH ratio as
      indicator of oxidative stress, and higher sinusoidal lactate dehydrogenase (LDH)
      efflux compared to control values, assessed under normoxic conditions. Perfused
      livers from control animals subjected to ischemia-reperfusion exhibited
      significant increases in the TBARS/GSH ratio and in the sinusoidal LDH efflux
      over values obtained under normoxic conditions, concomitantly with the appearance
      of small foci of necrotic cells in centrilobular and midzonal areas of the liver
      lobule. These parameters were further modified in the liver of hyperthyroid rats
      subjected to ischemia-reperfusion, with elevations in the TBARS/GSH ratio and in
      the sinusoidal LDH efflux largely exceeding the sum of effects elicited by
      hyperthyroidism or ischemia-reflow alone. In this situation, liver injury was
      more pronounced than in control rats, being characterized by multifocal areas of
      necrotic cells, irregularly distributed in the hepatic lobule, with lymphoid and
      macrophagic reaction. It is concluded that the concurrence of the hepatic
      mechanisms related to the oxidative stress underlying thyroid calorigenesis and
      ischemia-reoxygenation exacerbates liver injury, which seems to be mediated by
      potentiation of the prooxidant state of the organ.

PMID- 9165295
TI  - Increased uptake of LDL by oxidized macrophages is the result of an initial
      enhanced LDL receptor activity and of a further progressive oxidation of LDL.
AB  - Iron ions were recently shown to induce cellular lipid peroxidation in
      macrophages, and these oxidized cells can convert native low-density lipoprotein
      (LDL) to oxidized LDL (Ox-LDL). The present study demonstrates that deoxycholic
      acid (DCA) and angiotensin II (ANG-II) can also induce oxidative modification of
      macrophages via metal ions independent mechanisms. Furthermore, incubation of LDL
      (200 micrograms of protein/ml) for 24 h at 37 degrees C with DCA, ANG-II, as well
      as FeSO4-induced oxidized macrophages, resulted in oxidative modification of the
      lipoprotein as evidenced by increased TBARS formation in LDL (by 50, 105, and
      258%, respectively), decreased TNBS reactivity (by 45, 56, and 42%,
      respectively), and increased cellular uptake (by 60, 166, and 230%,
      respectively). A positive correlation (n = .88) was found between the extent of
      the cellular lipid peroxidation and the increment in the cellular uptake of the
      LDL. The oxidative modification of LDL by oxidized macrophages was found to be a
      progressive process. Incubation of LDL with oxidized macrophages for increasing
      periods of time up to 24 h resulted in progressive increment in: (1) the
      electrophoretic mobility of the LDL; (2) the TBARS formation in LDL; (3) the
      cellular uptake of LDL by the oxidized macrophages via the Ox-LDL receptor. Upon
      fractionation on a heparin-sepharose column of LDL that was incubated for
      different periods of time with oxidized macrophages, a gradual increment in the
      unbound LDL fraction was obtained, up to 72% after 24 h of incubation. During the
      first hour of LDL incubation with the oxidized macrophages a twofold increase in
      the cellular uptake of LDL by these cells was detected, although no significant
      oxidation of the lipoprotein occurred during this short time period. This effect
      could be attributed to an increased number of LDL receptors on the cell surface
      of the oxidized macrophages. In conclusion, increased uptake of LDL by oxidized
      macrophages results from two routes: (1) enhanced uptake via the LDL receptor due
      to increased LDL receptor activity; (2) lipoprotein uptake via the Ox-LDL
      receptors due to cellular modification of LDL. Both of these processes lead to
      macrophage cholesterol accumulation and foam cell formation, and thus contribute
      to accelerated atherosclerosis under oxidative stress.

PMID- 9165294
TI  - Effect of oxidative stress by iron on 4-hydroxynonenal formation and
      proliferative activity in hepatomas of different degrees of differentiation.
AB  - It has been shown previously that oxidative stress by ferrous iron in vitro leads
      to an inhibition of proliferation of murine ascites tumour cells in vivo. This
      effect is associated with increased lipid peroxidation in terms of formation of
      the highly reactive aldehyde 4-hydroxynonenal (HNE), which has been shown to
      inhibit the proliferation of numerous tumours and to induce differentiation. It
      was the purpose of this article to study the occurrence and metabolism of HNE and
      its inducibility by oxidative stress in hepatomas of different degrees of
      differentiation to find further evidence for a possible role of HNE in
      proliferation and/or differentiation, because it is known that in hepatoma cells
      with a very low degree of differentiation basal lipid peroxidation is hardly
      detectable, while in normal hepatocytes the basal level of thiobarbituric acid
      reactive substances (TBArS) is rather high. MH1C1 hepatoma cells and Yoshida AH
      130 hepatoma cells were chosen as highly differentiated and poorly differentiated
      tumour cells, respectively, and rat hepatocytes served as a control for normal
      liver phenotype. Ferrous histidinate (Fe/His) did not have a cytotoxic effect on
      Yoshida and MH1C1 cells, as measured by the LDH release test. In cell culture
      studies Fe/His revealed a dose dependent inhibition of the proliferation of
      Yoshida cells. The incorporation of 3H-thymidine into DNA of these cells was also
      inhibited by Fe/His in a dose-dependent manner, while the precursor uptake into
      the cytoplasm was unaffected. The basal levels of HNE were in the order:
      hepatocytes > MH1C1 cells > Yoshida cells. Both hepatocytes and Yoshida cells
      responded to the presence of Fe/His with increased formation of TBArS. Compared
      with hepatocytes the response of the Yoshida cells was greatly reduced. The
      response of cells to Fe/His with respect to HNE formation was decreased in the
      order: hepatocytes > MH1C1 cells > Yoshida cells, but in this case the
      differences were not very pronounced. The metabolic capacity of the cells to
      consume HNE was also decreased in the order: hepatocytes > MH1C1 cells > Yoshida
      cells. In this case the differences were very pronounced. These findings support
      the view that Yoshida cells with a low degree of differentiation and a low basal
      level of HNE are released from an inhibitory effect of HNE operative in
      hepatocytes and that HNE is causally involved in the iron induced inhibition of
      proliferation of poorly differentiated hepatoma cells.

PMID- 9165296
TI  - Oxidant generation with K(+)-induced depolarization in the isolated perfused
      lung.
AB  - This study evaluated whether cell membrane depolarization can induce oxidant
      generation in the isolated perfused rat lung as has been demonstrated with bovine
      pulmonary artery endothelial cells. Depolarization was produced by perfusing the
      lungs with high [K+] or with glyburide and was evaluated with bis-oxonol lung
      surface fluorometry. Lung surface bis-oxonol fluorescence increased above
      baseline (at 5.9 mM K+) by 18.5% with 24 mM K+, 35% with 48 mM K+, and 67% with
      96 mM K+, indicating graded membrane depolarization, and by 75% during perfusion
      with 10 microM glyburide. Oxidant generation was evaluated with hydroethidine
      lung surface fluorometry, and with assay of tissue thiobarbituric acid reactive
      substance (TBARS), conjugated dienes, and perfusate H2O2. Depolarization by high
      K+ or glyburide led to significant increases in generation of tissue oxidants and
      lipid peroxidation. Bodipy-FL-glyburide microfluorography showed localization of
      glyburide binding primarily to vascular endothelial cells vascular and airway
      smooth muscle cells, alveolar type II cells, and to nonciliated cells of the
      airway epithelium. These results indicate that cellular depolarization is
      associated with oxidant generation by the lung and suggests a role for K(+)
      channels in these events.

PMID- 9165297
TI  - Lipid peroxidation in photodynamically stressed mammalian cells: use of
      cholesterol hydroperoxides as mechanistic reporters.
AB  - Photodynamic action of merocyanine 540, an antileukemic sensitizing dye, on
      murine L1210 cells results in the formation of lipid hydroperoxides and loss of
      cell viability. High-performance liquid chromatography with mercury cathode
      electrochemical detection was used for determining lipid oxidation products,
      including the following cholesterol-derived hydroperoxides: 5 alpha-OOH, 6 alpha
      OOH, 6 beta-OOH, and unresolved 7 alpha, 7 beta-OOH. Among these species, 5 alpha
      , 6 alpha-, and 6 beta-OOH (singlet oxygen adducts) were predominant in the early
      stages of photooxidation, whereas 7 alpha- and 7 beta-OOH (products of free
      radical reactions) became so after prolonged irradiation or during dark
      incubation after exposure to a light dose. These mechanistic changes were studied
      in a unique way by monitoring shifts in the peroxide ratio, i.e., 7-OOH/5 alpha
      OOH, or 7-OOH/6-OOH. When cells (10(7)/ml) were exposed to a visible light
      fluence of 0.6 J/cm2 in the presence of 10 microM merocyanine 540, 7-OOH/5 alpha
      OOH increased by approximately 100% after 2 h of dark incubation at 37 degrees C.
      The increase was much larger (approximately 250%) when cells were photooxidized
      after treatment with 1 microM ferric-8-hydroxyquinoline, a lipophilic iron donor,
      whereas no increase was observed when cells were pretreated with 100 microM
      desferrioxamine, an avid iron chelator/redox inhibitor. Correspondingly,
      postirradiation formation of thiobarbituric acid-reactive material was markedly
      enhanced by ferric-8-hydroxyquinoline and suppressed by desferrioxamine, as was
      the extent of cell killing. When added to cells after a light dose, chain
      breaking antioxidants such as butylated hydroxytoluene and alpha-tocopherol
      strongly protected against cell killing and slowed the increase in 7-OOH/5 alpha
      OOH ratio. It is apparent from these results that (1) the 7-OOH/5 alpha-OOH or 7
      OOH/6-OOH ratio can be used as a highly sensitive index of singlet oxygen vs.
      free radical dominance in photodynamically stressed cells; and (2) that
      postirradiation chain peroxidation plays an important role in photodynamically
      initiated cell killing.

PMID- 9165298
TI  - Age-related changes in the peroxyl radical scavenging capacity of human plasma.
AB  - Aging and the diseases that typically follow with increasing age, notably
      atherosclerosis and cancer, are often proposed to be involved in increased
      oxidative stress. Animal studies, on the other hand, show no clear-cut pattern of
      age-related changes in enzymatic antioxidant defences. In this study we have
      demonstrated that total peroxyl radical scavenging antioxidant capacity (TRAP) in
      human plasma changes with age. We also found that among the antioxidants in human
      plasma there exists a major fraction of so far unidentified antioxidant(s). A
      chemiluminescent TRAP assay was used to determine the presence of peroxyl radical
      scavenging antioxidants in human plasma. The material consisted of 87 healthy
      volunteers, aged 20-96 years, who used no regular medication, vitamins, or trace
      elements. In females, total antioxidant capacity increased significantly during
      the life span. The increase in TRAP was mainly due to unidentified antioxidants.
      In males, TRAP increased until age 51-74, and then significantly decreased. The
      decrease observed among males was also due to the sharp decline in the
      concentration of unidentified antioxidants.

PMID- 9165299
TI  - Retarding effect of dietary restriction on the accumulation of 8-hydroxy-2'
      deoxyguanosine in organs of Fischer 344 rats during aging.
AB  - An age-related accumulation in rats of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a
      marker of oxidative DNA damage, and the effect of dietary restriction on the
      accumulation of 8-OHdG were examined. The 8-OHdG concentrations of nuclear DNA in
      organs of ad libitum fed rats were similar in young and middle age, but increased
      significantly in kidney at 24 months of age, in heart and liver at 27 months of
      age, and in brain at 30 months of age. The 8-OHdG concentration in dietary
      restricted rats showed no changes in any organ up to 30 months of age and then
      was increased at 33 months of age. Dietary restriction retarded the onset of the
      age-related increase in 8-OHdG concentration, although it did not reduce the
      concentration in young and middle age. These results suggest that the effect of
      dietary restriction on the extension of life-span in rats might be related to a
      reduction in oxidative damage.

PMID- 9165300
TI  - Oxidative modifications of apoB-100 by exposure of low density lipoproteins to
      HOCL in vitro.
AB  - Although the products of oxidation of the lipid components of LDL have been
      studied extensively, much less is known about the specific products of oxidative
      modification of the apoprotein. We reacted native LDL and LDL that had been
      treated with HOCl with 2,4-dinitrophenylhydrazine (DNPH), delipidated and
      trypsinized the protein, and analyzed the products by HPLC. Although tryptic
      digests of native LDL and LDL oxidized by limited quantities of HOCl showed
      similar patterns by HPLC with detection at 220 nm, oxidized LDL showed several
      discrete peaks at 365 nm, which is characteristic of hydrazones formed with
      aldehydes and ketones, commonly termed protein carbonyls. Native LDl showed no
      peaks in the chromatograms at 365 nm. Peptides absorbing at 365 nm were isolated
      by HPLC and characterized. In most cases, the probable sites of modification on
      the peptides could be implied by failure of an anticipated amino acid to appear
      in the expected sequence. Of the 14 peptides isolated and characterized to date,
      eight peptides contained Cys residues. In other peptides, Lys, Trp, and Met were
      identified as amino acid residues apparently modified by HOCl treatment of LDL.
      Thirteen of the peptides identified are from trypsin-releasable peptides located
      on the surface of unoxidized native LDL. Our studies suggest a selective process
      of modification of apoB-100 by HOCl and the approaches used in the present
      studies should be useful for the characterization of the mechanisms of oxidation
      of this and other proteins.

PMID- 9165301
TI  - Appearance of 1-2 Mbp giant DNA fragments as an early common response leading to
      cell death induced by various substances that cause oxidative stress.
AB  - The effects of oxidative stress on double strand DNA breakage were examined in T
      24 human bladder tumor cells using various active oxygen producing agents such as
      hydrogen peroxide (H2O2), bleomycin (BLM), neocarzinostatin (NCS), and x-ray
      irradiation. Analysis of the DNA by pulsed-field gel electrophoresis (PFGE)
      revealed that discrete giant DNA fragments of 1-2 Mbp and 200-800 kbp had
      accumulated in the nuclei of the treated cells. The 1-2 Mbp giant DNA fragments
      were first observed 2 h after the T-24 cells were exposed to the active oxygen
      producing agents, or irradiated with x-ray. The appearance and the amounts of 1-2
      Mbp and 200-800 kbp giant DNA fragments seemed to depend on the concentration and
      the type of reagents used or the dose of x-ray. Following the accumulation of
      giant DNA fragments, another type of DNA fragmentation was detected and DNA
      fragments smaller than 100 kbp accumulated in the nuclei of the cells irradiated
      with x-ray or treated with NCS. In addition, DNA ladder formation, which is
      characteristic of apoptosis, was observed. The giant DNA fragments appeared to
      arise as a consequence of double-stranded DNA breakage, which occurred earlier
      than cell lysis, as assessed by 51Cr release. These findings indicate that the
      formation of giant DNA fragments is a specific characteristic of cells responding
      to oxidative stress, and it may be an initial event that leads to cell death.

PMID- 9165302
TI  - Role of glutathione metabolism and apoptosis in the regression of liver
      hemopoiesis.
AB  - Although apoptosis has been believed to play important roles in ontogenic
      development of animals, the molecular mechanism that triggers the regression of
      liver hemopoiesis during perinatal period is not known. Apoptosis is induced by
      many factors, such as decrease in growth factors and increased oxygen stress.
      Because hepatic gamma-glutamyltransferase (GGT) changes markedly during the
      perinatal period of a rodent, metabolism of glutathione (GSH), a naturally
      occurring major antioxidant, might change significantly in and around liver
      cells. To know the possible involvement of apoptosis and GSH metabolism in the
      regression of hemopoiesis, hepatocytes and hemopoietic cells were isolated from
      fetal rat liver. Biochemical analysis revealed that, during the perinatal period,
      hepatic GGT levels transiently increased predominantly with hepatocytes,
      suggesting a marked change in thiol status in and around these cells. Cell
      culture analysis revealed that hemopoietic cells but not hepatocytes exhibited a
      marked apoptosis in a thiol-free medium, as judged from DNA fragmentation. The
      apoptosis of hemopoietic cells was inhibited by various thiols, such as L
      cysteine, N-acetyl-L-cysteine (NAC), and GSH. These observations suggested that a
      marked change in GSH status in and around liver cells might play critical roles
      in triggering apoptosis of hemopoietic cells, thereby enhancing the regression of
      liver hemopoiesis.

PMID- 9165303
TI  - Binding of iron to neuromelanin of human substantia nigra and synthetic melanin:
      an electron paramagnetic resonance spectroscopy study.
AB  - The binding of iron by melanin is a potentially important phenomenon as detailed
      knowledge of this binding is essential for understanding the role of melanin and
      iron in the pathogenesis of oxidative damage in the substantia nigra. Electron
      paramagnetic resonance spectroscopy is one of the most useful approaches in the
      investigation of melanins and their interaction with iron. This study was
      undertaken to obtain systematic data on the effects of ferric iron on the
      electron paramagnetic resonance spectra of neuromelanin and synthetic models of
      neuromelanin. Data from the latter can potentially be used to infer as to the
      state of neuromelanin in the human substantia nigra. The results of this study
      indicate that the spectra at g = 4.3, attributable to Fe3+, provides a useful
      parameter for determining the amount of paramagnetic iron bound to melanin. These
      data together with the magnitude of the free radical signal from melanin provides
      an indication of the amount of iron bound to neuromelanin in intact human
      substantia nigra. After binding to melanin, the iron can change its location
      and/or state, which is indicated by the change in the microwave power saturation
      that occurs gradually after the binding of the iron. At least part of this
      process could occur at low temperatures (i.e., during storage at -15 degrees C).

PMID- 9165304
TI  - Overexpression of plasma membrane annexin II in NO2-exposed pulmonary artery
      endothelial cells.
AB  - Because exposure to nitrogen dioxide (NO2) alters plasma membrane structure and
      function in pulmonary artery endothelial cells (PAEC), we examined whether NO2
      exposure is associated with upregulation of plasma membrane-specific proteins in
      PAEC. Exposure to 5 ppm NO2 for 24 h had no significant effect on total protein
      synthesis. However, two-dimensional gel electrophoresis of isolated plasma
      membranes from [35S]-methionine pulse-labeled PAEC exposed to NO2 for 24 h
      demonstrated 3- to 9-fold increases in the synthesis of several proteins with
      molecular masses of 36, 39, and 40 kDa compared with controls. N-terminal amino
      acid sequencing and immunodetection analysis identified the 36kDa plasma membrane
      protein as annexin II (lipocortin II). Northern blotting analysis demonstrated
      that the mRNA expression for annexin II in NO2-exposed cells was also increased.
      These results suggest that exposure to NO2 results in induction of plasma
      membrane annexin II, an important multifunctional calcium- and phospholipid
      binding protein in PAEC.

PMID- 9165305
TI  - Antioxidant enzymes in malignant prostate cell lines and in primary cultured
      prostatic cells.
AB  - The antioxidant enzymes catalase, glutathione reductase (GR), glutathione S
      transferase (GST), glutathione peroxidase (GPx), and superoxide dismutase (SOD)
      were determined in the androgen-response LNCaP and androgen-nonresponsive PC-3
      and DU 145 cells as well as in prostatic epithelial cell cultures of benign and
      malignant human prostatic tissue. There were no differences between the enzyme
      activities of the human primary cell cultures from cancerous tissue and their
      normal counterparts. The enzyme activities of the three permanent cell lines were
      either higher (SOD, catalase, GR) or lower (GST, GPx) than in the primary cell
      cultures. In LNCaP cells catalase and GR were significantly higher, GST, in
      contrast, was significantly lower than in PC-3 and DU 145 cells. GST in PC-3 and
      DU 145 cells, and SOD in all the three cell lines showed no significant
      differences. Catalase, GPx and GR values were significantly different in the
      three permanent cell lines. The different enzymatic equipment of the prostate
      cancer cell lines provides the basis for experimental testing of new concepts of
      cancer treatment with the help of systematic modulations of the antioxidant
      defence systems in prostate cancer.

PMID- 9165306
TI  - Oxidative stress hypothesis in Alzheimer's disease.
AB  - The major hurdle in understanding Alzheimer's disease (AD) is a lack of knowledge
      about the etiology and pathogenesis of selective neuron death. In recent years,
      considerable data have accrued indicating that the brain in AD is under increased
      oxidative stress and this may have a role in the pathogenesis of neuron
      degeneration and death in this disorder. The direct evidence supporting increased
      oxidative stress in AD is: (1) increased brain Fe, Al, and Hg in AD, capable of
      stimulating free radical generation; (2) increased lipid peroxidation and
      decreased polyunsaturated fatty acids in the AD brain, and increased 4
      hydroxynonenal, an aldehyde product of lipid peroxidation in AD ventricular
      fluid; (3) increased protein and DNA oxidation in the AD brain; (4) diminished
      energy metabolism and decreased cytochrome c oxidase in the brain in AD; (5)
      advanced glycation end products (AGE), malondialdehyde, carbonyls, peroxynitrite,
      heme oxygenase-1 and SOD-1 in neurofibrillary tangles and AGE, heme oxygenase-1,
      SOD-1 in senile plaques; and (6) studies showing that amyloid beta peptide is
      capable of generating free radicals. Supporting indirect evidence comes from a
      variety of in vitro studies showing that free radicals are capable of mediating
      neuron degeneration and death. Overall, these studies indicate that free radicals
      are possibly involved in the pathogenesis of neuron death in AD. Because tissue
      injury itself can induce reactive oxygen species (ROS) generation, it is not
      known whether this is a primary or secondary event. Even if free radical
      generation is secondary to other initiating causes, they are deleterious and part
      of a cascade of events that can lead to neuron death, suggesting that therapeutic
      efforts aimed at removal of ROS or prevention of their formation may be
      beneficial in AD.

PMID- 9165308
TI  - Palladium or platinum exacerbates hydroxyl radical mediated DNA damage.
AB  - Strand breakage of supercoiled pBR322 DNA by a Fenton system is increased in the
      presence of palladium or platinum (Pt) ions. Neither Pd nor Pt ions can
      substitute for iron in the Fenton system. We have obtained several lines of
      evidence that Pd and Pt ions in the presence of a Fenton system can augment the
      production of OH., as monitored by a spectrophotometric method quantifying
      hydroxylated salicylate or by a fluorometric method quantifying catechol
      production. Furthermore, the promoting effect of both metal ions on OH.
      production was substantiated by the identification of multiple hydroxylated
      products of salicylate [2,3-dihydroxybenzoate (A), 2,5-dihydroxybenzoate (B), and
      catechol (C)] using HPLC. The concentrations of A, B, and C produced in the
      control were 4.5, 8.0, and 2.0 microM, respectively; whereas, their respective
      concentrations increased to 23.6, 42.0 and 10.0 microM with the addition of Pd
      ions. The observed phenomenon was further confirmed by the identification of HO
      DMPO spin adducts using ESR spectroscopy. Taken together, our data suggest that
      the mechanism of Pd or Pt ion-mediated exacerbation of DNA damage by a Fenton
      system is due to the promotion of OH. production by these metal ions.

PMID- 9165307
TI  - Singlet oxygen involvement in ultraviolet (254 nm) radiation-induced formation of
      8-hydroxy-deoxyguanosine in DNA.
AB  - In the present article, we report that ultraviolet (UV 254 nm) radiation
      substantially induced the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in
      purified DNA. The formation of 8-OHdG, a hallmarker of oxidative DNA damage,
      increased linearly up to 25 kJ/m2 and was dependent on the presence of oxygen in
      the solution. Deoxygenation by nitrogen significantly reduced the yield of 8-OHdG
      by UV radiation, whereas oxygenation with 100% oxygen substantially enhanced the
      yield. The hydroxyl radical (HO.) scavenger dimethysulfoxide (DMSO) dramatically
      quenched the formation of 8-OHdG by the ionizing radiation and Fenton reaction,
      but enhanced the formation of UV-induced 8-OHdG. Further studies showed that DMSO
      and mannitol, two predominant HO. scavengers, enhanced the levels of UV-induced 8
      OHdG in a dose-dependent fashion, suggesting that UV-induced 8-OHdG is
      independent of the generation of HO.. The use of deuterium oxide (D2O), which
      prolongs the half life of singlet oxygen (1O2), substantially enhanced the yield
      of 8-OHdG by UV radiation, but not that by Fenton reaction. In contrast, sodium
      azide, a more and less specific 1O2 quencher, substantially reduced the levels of
      8-OHdG by both UV radiation and Fenton reaction, indicating that sodium azide
      lacks the quenching specificity of 1O2 and HO.. It is proposed that UV induced 8
      OHdG proceeds through a singlet oxygen involvement mechanism, rather than the
      generation of hydroxyl radicals.

PMID- 9165309
TI  - Effect of reactive oxygen species on the elastin mRNA expression in cultured
      human dermal fibroblasts.
AB  - The effects of ultraviolet A (UVA) and reactive oxygen species (ROS), generated
      by a xanthine and xanthine oxidase (XOD) system, on the mRNA expression of
      elastin, were investigated using cultured human dermal fibroblasts. Total RNA was
      isolated and subjected to Northern blot analysis using synthesized 530 base cDNA
      probe for elastin with primers derived from exon 10 and 1 of human elastin. UVA
      irradiation did not affect elastin mRNA expression. In contrast, ROS resulted in
      a dose-related increase in the level of elastin mRNA up to 1.8-fold in cultured
      human dermal fibroblasts. Catalase, used as scavenger, essentially prevented the
      ROS induced alterations in elastin mRNA levels. These results suggest that ROS
      produced in the dermis may contribute to elastin deposition observed in
      photoaging skin.

PMID- 9165310
TI  - Instantaneous analysis of aldehydes in biological fluids using a spray interface
      coupled to a mass spectrometer.
AB  - A new interface coupled to a mass spectrometer was developed for the direct
      analysis of volatile organic compounds from small volumes of aqueous samples,
      including blood or tissue homogenates (St-Germain et al. 1995, Anal. Chem.
      67:4536-4541). The greatest advantages of our system are minimal sample
      treatment, an instantaneous response time coupled with detection limits in the
      range of < 1 ppb for most compounds. For the analysis of low-molecular weight
      aldehydes, such as formaldehyde, acetaldehyde, propanal, and hexanal, lower
      detection limits were obtained when samples were converted to methoxime
      derivatives prior to injection. The detection limit for hexanal in water or Krebs
      Ringer solution was 0.01 microM (10 pmol injected). The reproducibility of
      replicate injections was 4.4%. The usefulness of our system was illustrated by
      measuring aldehyde accumulation in peroxidized solutions of polyunsaturated fatty
      acids and rat tissue homogenates. Data confirmed that peroxidation of omega-3
      fatty acids produces propanal, whereas omega-6 fatty acids form hexanal.
      Peroxidation of heart and brain homogenates formed predominantly propanal.
      However, the recovery of hexanal after sample treatment with methoxylamine
      depended on the derivatization time and temperature, suggesting that this
      aldehyde may form Schiff base linkages. These results show that spray extraction
      coupled to mass spectrometry provides a quick (< 1 min), clean and reproducible
      way to detect aldehydes produced from lipid peroxidation in aqueous samples.

PMID- 9165311
TI  - Stimulation of hepatocyte glycerolipid synthesis by iron/ADP is due to ADP rather
      than oxidative stress.
AB  - ADP-complexed Fe3+ has been used in various in vitro systems and in intact cells
      to induce lipid peroxidation. During studies on the effects of oxidative stress
      on lipid metabolism we observed a significant increase in de novo glycerolipid
      synthesis in Fe3+/ADP-treated rat hepatocytes as evidenced by increased [U
      14C]glycerol incorporation. Here we show that this increase, largely due to
      enhanced triacylglycerol synthesis, is caused by ADP rather than Fe3+/ADP-induced
      oxidative stress. Hence, metabolic alterations due to treatment of intact cells
      by Fe3+/ADP must be interpreted with caution.

PMID- 9165312
TI  - Neopterin derivatives to activate NF-kappa B.

PMID- 9165313
TI  - Complications and their impact after pneumatic dilation for achalasia:
      prospective long-term follow-up study.
AB  - BACKGROUND: With the exception of esophageal perforations, complications of
      pneumatic dilation are incompletely defined. This study analyzes the incidence of
      all complications of this procedure and their impact on the patients' clinical
      course. METHODS: Sixty-seven consecutive patients with achalasia underwent
      pneumatic dilation with a Browne-McHardy dilator. Patients were observed for 24
      hours after treatment and evaluated 4 weeks later as well as at 2-year intervals
      for a mean follow-up period of 4.9 +/- 3.8 years. In patients with and without
      complications, the length of remission was evaluated by Kaplan-Meter life table
      analysis. RESULTS: Twelve patients (18%) developed morphologic complications
      consisting in one perforation, two intramural hematomas, and nine diverticula at
      the gastric cardia. Ten patients (15%) complained of prolonged postdilation chest
      pain. The 5-year remission rate in the latter patients was 51% compared to 42%
      for patients without complications and 11% for patients developing traumatic
      diverticula. Surgery was ultimately performed in one third of all patients, a
      rate that remained unaffected by the type of complication. CONCLUSIONS:
      Complications of pneumatic dilation are underestimated and underreported. More
      than 30% of all patients develop either prolonged pain or morphologic lesions.
      Although prolonged pain does not indicate an unfavorable prognosis, the
      appearance of diverticula may be associated with a shorter clinical remission.

PMID- 9165314
TI  - An objective end point for dilation improves outcome of peptic esophageal
      strictures: a prospective randomized trial.
AB  - BACKGROUND: The usual end point for defining success of dilation is subjective
      (relief of dysphagia). In most patents thus managed strictures recur. We asked
      whether an objective end point would improve outcome. METHODS: After dilation to
      15 mm, patients were randomized into subjective and objective groups. In
      subjective group patients, end point for dilation was alleviation of dysphagia;
      in objective group patients, passing the 12 mm barium pill test. Objective group
      patients who failed underwent redilation until they passed the pill or failed
      three times. During Part 1 of the study, patients received ranitidine, during
      Part 2 they received omeprazole. RESULTS: In part 1, dysphagia was alleviated in
      7 of 8 subjective group patients. Only 2 of 10 objective group patients passed
      the pill test and no additional patients passed after 3 sessions, although most
      had no dysphagia. In Part 2, 19 subjective groups and 15 objective group patients
      were studied. End point was not achieved in 3 objective group patients. Over long
      term follow-up, objective group patients had less recurrent dysphagia (p = 0.02)
      and required fewer redilation sessions (p < 0.05). Overall, the pill test
      correlated with the presence or absence of dysphagia (P < 0.001). Predictive
      value of passing the pill 1 week after dilation for the absence of dysphagia was
      100%, but of failing the pill test and the presence of dysphagia was only 18%.
      CONCLUSIONS: Achieving an objective end point reduces stricture recurrence and
      the need for subsequent dilation. Initial subjective improvement does not predict
      long-term success.

PMID- 9165315
TI  - Esophageal self-expandable metallic stents--indications, practice, techniques,
      and complications: results of a national survey.
AB  - BACKGROUND: The gastroenterology community's experience with esophageal self
      expandable metallic stents (SEMS) is unknown. METHODS: In order to assess
      indications, perioperative management, and self-reported complications associated
      with SEMS placement, a survey was mailed to ASGE members. RESULTS: Of 3414
      surveys mailed, 212 (6.2%) were completed and returned. One hundred twenty-eight
      physicians had experience with a total of 434 SEMS. Most physicians practiced in
      the private sector (72%), and 75% had placed 3 or fewer SEMS. Perceived ease of
      placement was the most common reason for choosing a SEMS (55%). Fluoroscopic and
      endoscopic guidance was used by 83% of respondents, and 81% allowed liquid diet
      after correct position and patency had been confirmed; 56% of respondents
      discharged their patients within 24 hours of SEMS placement. The rates of failure
      for full expansion (7.1%), stent misplacement (4.8%), and failure to deploy (3%)
      were higher than previously reported. Acute patient complications and delayed
      bleeding occurred less frequently than in reported series but mortality rates
      were similar. CONCLUSIONS: Ease of placement is the main reason for choosing a
      SEMS. Differences in complication rates, compared to previous studies on SEMS,
      may be related to operator experience and protocol requirements. When compared to
      plastic stents, complications were less frequent.

PMID- 9165316
TI  - The role of ERCP in biliary atresia.
AB  - BACKGROUND: It is not easy to discriminate between infantile hepatitis and
      biliary atresia in spite of several diagnostic tests including laboratory
      analyses, ultrasound, and hepatobiliary scans. ERCP is the most useful procedure
      for visualization of the extrahepatic biliary system, but ERCP is still an
      uncommon procedure in children. METHODS: ERCP examination was performed in 52
      infants with biliary atresia (10 with infantile hepatitis, 5 with congenital
      biliary dilatation, 3 with paucity of intrahepatic bile duct, 2 with duodenal
      atresia, and 1 with postoperative jaundice of hepatoblastoma) aged from 8 days to
      300 days (mean, 71 days). RESULTS: ERCP was successful in 47 with biliary
      atresia, in 9 with infantile hepatitis, and 10 with another disease. Liver biopsy
      was performed in 1 infant with hepatitis in whom the cannulation failed; in 9
      with hepatitis in whom the cannulation was successful, exploratory laparotomy
      could be avoided. The ERCP findings in 46 patients with biliary atresia
      (excluding 1 in whom evaluation could not be performed because of poor x-ray
      quality) were classified into four patterns. CONCLUSIONS: A success rate of ERCP
      examinations in infants was 88%, so ERCP is recommended to make a correct
      decision regarding the need for surgery in cholestatic disorders.

PMID- 9165317
TI  - Endoscopic findings in hypertrophic pyloric stenosis: appearance in classic and
      evolving disease.
AB  - BACKGROUND: Hypertrophic pyloric stenosis (HPS) is the most common abdominal
      surgical disorder in infants. Although the majority of cases are diagnosed by
      ultrasound, equivocal cases may require endoscopy. This study was performed to
      assess the various endoscopic appearances of HPS in infants. METHODS: A
      prospective study comparing the endoscopic appearance of the antrum and pylorus
      of 18 children with HPS to 21 children in a normal control group. RESULTS: Antral
      or pyloric mucosal hypertrophy was visualized endoscopically in all 18 study
      patients. The degree of mucosal thickening varied depending on the age of
      presentation and duration of symptoms. Antral fold hypertrophy was first noted at
      10 days of age, and in the oldest patient (4 months of age) a pyloric mass was
      noted. By comparison, 21 control infants had no evidence of antral or pyloric
      narrowing or mucosal thickening. CONCLUSIONS: Upper endoscopy can be a valuable
      adjunctive diagnostic tool in select cases of HPS when imaging tests are
      inconclusive or when infants present with clinical symptoms outside the typical
      age-time frame for HPS. Because HPS may evolve over time, it is important that
      the endoscopist recognize the different appearances of HPS.

PMID- 9165318
TI  - Use of conscious sedation for lower and upper gastrointestinal endoscopic
      examinations in children, adolescents, and young adults: a twelve-year review.
AB  - BACKGROUND: Over the past decade, many pediatric endoscopists have replaced
      general anesthesia with conscious sedation. Sedation is commonly used to minimize
      discomfort. METHODS: To evaluate the safety and efficacy of conscious sedation we
      reviewed 2711 reports of lower and upper gastrointestinal endoscopic examinations
      performed in 2026 patients between July 1981 and December 1992. RESULTS:
      Intravenous sedation was accomplished using meperidine and diazepam (914
      examinations, 35%) or meperidine and midazolam (1427 examinations, 55%). Single
      agents were used for 83 examinations (3%), and 96 examinations (3.5%) were
      performed with the patient under general anesthesia. In the lower endoscopy group
      sedated intravenously (n = 713), the cecum was reached in 82% of examinations.
      The procedure could not be completed in 17 cases in which patients were
      uncooperative despite sedation. In the upper endoscopy group sedated
      intravenously (N = 1653), all but 91 endoscopies were completed to the descending
      duodenum. Esophagoscopy had been planned in 76% of these procedures. Minor
      complications occurred in 7 patients (0.3%). This included two episodes of
      significant oxygen desaturation that responded to oxygen administration and
      narcotic reversal. A major complication occurred in 1 patient (0.04%) who had a
      gastric perforation during esophageal dilation over a defective guide wire. There
      were no deaths, episodes of cardiorespiratory arrest, or pulmonary aspirations in
      our series. The combined major and minor complication rate was 0.3%. CONCLUSIONS:
      Intravenous conscious sedation is safe and effective in children undergoing
      endoscopic examination of the gastrointestinal tract. Selected patients will
      require general anesthesia.

PMID- 9165319
TI  - Relation between endoscopic ultrasound findings and outcome of patients with
      tumors of the esophagus or esophagogastric junction.
AB  - BACKGROUND: Endoscopic ultrasound (EUS) is considered to be the best staging
      technique for cancer of the esophagus or the esophagogastric junction. This study
      evaluates the relation between preoperative EUS staging results of these tumors
      and survival. It also examines how EUS staging predicts resectability. METHODS:
      Survival data of 86 patients who underwent EUS for staging of tumors of the
      esophagus or esophagogastric junction were analyzed. Most patients (78 of 86)
      were treated surgically (73 resections, 5 bypasses). Eight patients did not
      undergo surgery. RESULTS: Survival of patients was significantly related to EUS T
      staging (log rank test: p = 0.05), EUS N staging (p = 0.02), detection of celiac
      lymph node metastasis (p = 0.0027), and the presence of stenosis (p = 0.02).
      Also, the endosonographic AJCC classification was significantly related to
      survival (p = 0.0012). Total accuracy for T staging amounted to 59%. Accuracy for
      recognition of transmural growth was 82%. There was a good association between
      endosonographic findings (EUS stage II, absence of lymph nodes) and the
      possibility of complete resection. Incomplete resection was less well predicted.
      CONCLUSION: Survival of patients with tumors of the esophagus or esophagogastric
      junction is strongly related to EUS TNM staging results. Tumor resectability is
      related to endosonographic findings. However, more advanced EUS findings do not
      necessarily predict unresectability.

PMID- 9165320
TI  - The clinical utility of endoscopic ultrasound-guided fine-needle aspiration in
      the diagnosis and staging of pancreatic carcinoma.
AB  - BACKGROUND: Endoscopic ultrasound (EUS) guided fine-needle aspiration (FNA) of
      pancreatic lesions is being increasingly used. Our aim was to determine the
      safety, accuracy, and clinical utility of EUS-guided FNA in both the diagnosis
      and staging of pancreatic cancer. METHODS: Forty-four patients (24 men/20 women)
      had EUS-guided FNA of pancreatic lesions (39 head/neck, 5 body, 3 tail) and/or
      associated lymph nodes. The mean age was 61 (range, 28 to 88 years). The
      indication for EUS-guided FNA was a pancreatic lesion seen initially on CT (39%),
      ERCP (43%), or EUS (18%). Follow-up data were collected on all patients for mean
      of 14.5 months (range 1 to 33 months). RESULTS: CT detected only 15 of 61 (25%)
      focal lesions seen by EUS, Adequate specimens were obtained by EUS-guided FNA in
      44 of 47 (94%) pancreatic lesions and 14 of 14 (100%) associated lymph nodes
      (overall adequacy was 95%). Of the 46 lesions in which specimens were adequate
      and a final diagnosis was available (32 malignant, 14 benign), EUS-guided FNA had
      a sensitivity of 92%, specificity of 100%, and diagnostic accuracy of 95% for
      pancreatic lesions and 83%, 100%, and 88% for lymph nodes, respectively. Six
      percent of pancreatic cases had inadequate specimens and, if included, lowered
      the sensitivity to 83%, specificity to 80%, and diagnostic accuracy to 88% for
      pancreatic lesions. In 3 patients with enlarged celiac nodes on EUS, EUS-guided
      FNA was able to make a tissue diagnosis of metastasis, which changed the
      preoperative staging and precluded surgery. EUS in combination with EUS-guided
      FNA precluded surgery in 12 of 44 (27%) and may have precluded surgery in an
      additional 6 of 44 (14%). EUS-guided FNA avoided the need for further diagnostic
      tests, thus expediting therapy in a total of 25 (57%) patients and influenced
      clinical decisions in 30 of 44 (68%) patients. The estimated cost savings based
      on surgeries avoided was approximately $3300 per patient. There was only one
      complication (2%), a post-FNA fever. CONCLUSION: EUS-guided FNA of the pancreas
      appears to be a safe and effective method that increases both the diagnostic and
      staging capability of EUS in pancreatic cancer. The clinical impact of EUS-guided
      FNA includes avoiding surgery and additional imaging studies with a substantial
      cost savings.

PMID- 9165321
TI  - Evaluation of the pattern of liver tests and yield of cholangiography in
      symptomatic choledocholithiasis: a prospective study.
AB  - BACKGROUND: The role of ERCP in the management of choledocholithiasis in an era
      of minimally invasive therapy continues to be defined. METHODS: We evaluated
      prospectively the pattern of liver test abnormalities and yield of
      cholangiography after presentation with illnesses suggesting choledocholithiasis.
      Ninety-four consecutive patients, all with liver test abnormalities (total
      bilirubin, alkaline phosphatase, AST, and ALT) at presentation, had serial
      determinations to within 24 hours of cholangiography and were divided into four
      groups based on their patterns of rise or fall of liver test results as well as
      presenting clinical syndrome. Group I: normalized liver tests; Group II: falling
      liver tests, and alkaline phosphatase falling greater than 50% of the difference
      between presentation value and upper limit of normal; Group III: alkaline
      phosphatase falling less than 50%; and Group IV: any liver test with increasing
      levels. Clinical syndromes included cholangitis, pancreatitis, combined
      cholangitis and pancreatitis, and biliary pain with abnormal liver tests.
      RESULTS: Yields of choledocholithiasis were 13% (Group I), 50% (Group II), 67%
      (Group III), and 94% (Group IV). Yield by syndromes were 36% (biliary
      pancreatitis), 72% (biliary pain and abnormal liver tests), 87% (cholangitis),
      and 100% (cholangitis and pancreatitis). CONCLUSION: The degree of decline in
      liver test levels is inversely related to the yield of cholangiography in
      symptomatic choledocholithiasis; the yield of ERCP in these patients (with
      normalized liver tests) is low and they do not require ERCP. Pre-ERCP estimates
      of the likelihood of choledocholithiasis can be made on the basis of the pattern
      of liver tests, and biliary pancreatitis patients with normalized liver tests do
      not require ERCP.

PMID- 9165322
TI  - Biliary manometry, bacterial characteristics, bile composition, and histologic
      changes fifteen to seventeen years after endoscopic sphincterotomy.
AB  - AIM: To evaluate the function of the biliary sphincter 15 to 17 years after
      endoscopic sphincterotomy and to investigate if loss of sphincter function is
      associated with bacterial colonization, changes in bile composition, or
      inflammation of the biliary system. METHODS: Eight patients who had undergone
      endoscopic sphincterotomy for bile duct stones 15 to 17 years previously
      underwent ERCP with biliary manometry, bile sampling, and biopsy. Manometry was
      performed using a perfused triple-lumen manometry catheter and a station pull
      through technique. Bile samples were cultured and analyzed for biliary lipids,
      bile salts, bacterial beta-glucuronidase, and phospholipase A2. Biopsy specimens
      were taken from the proximal common heptic duct for histologic examination.
      RESULTS: Manometry demonstrated absent basal sphincter pressure and no
      choledochoduodenal pressure gradient in all patients. Phasic contractions were
      observed in two patients. Cholangiography showed stones in one patient. Positive
      cultures were obtained in three patients, including the patient with stones. All
      bile samples showed a high content of biliary lipids and cholesterol. Some
      samples contained considerable amounts of hydrophobic bile salts. Five samples
      contained very high levels of phospholipase A2 activity. Significant bacterial
      beta-glucuronidase activity was found in one patient, the patient with stones.
      Biopsy specimens of the proximal common hepatic duct in three patients showed
      chronic inflammation with fibrosis and reactive epithelial changes. CONCLUSIONS:
      After endoscopic sphincterotomy for bile duct stones, the function of the biliary
      sphincter is permanently lost. This is associated with bacterial colonization,
      presence of cytotoxic components in the bile, and chronic inflammation of the
      biliary system.

PMID- 9165323
TI  - Drinking before endoscopy: milk or water?
AB  - BACKGROUND: The traditional fluid fast prior to endoscopy is unnecessary. We have
      previously shown that drinking water prior to endoscopy does not affect either
      the quality of mucosal views or residual gastric fluid volumes when compared to
      patients undergoing endoscopy after a standard fast. The present study was
      designed to establish whether milk, which may delay gastric emptying, could also
      be drunk prior to endoscopy without adverse effect. METHODS: Forty-eight patients
      (mean age 48 years, range 20 to 79) undergoing routine upper gastrointestinal
      endoscopy after overnight fast were randomized to drink 200 ml of either still
      mineral water or full fat milk. Endoscopy was performed 90 minutes later, when
      all residual gastric fluid was aspirated via the endoscope. Volume and pH of
      gastric aspirate were measured and the quality of the mucosal view at endoscopy
      recorded as poor, adequate, or excellent. RESULTS: No difference was shown
      between water (n = 27) and milk (n = 21) drinkers in residual gastric volume
      (mean +/- SEM, water vs milk) (16.0 ml +/- 1.5 vs 18.9 ml +/- 2.9) or pH (2.23 +/
      0.14 vs 2.48 +/- 0.14). Of those patients with poor, adequate, or excellent
      views, 4 of 4, 11 of 12, and 6 of 32 patients, respectively, were milk drinkers
      (chi-squared test for trend = 21.7, df = 1, p < 0.001), indicating significantly
      worse mucosal views in the group drinking milk. CONCLUSION: Drinking water up to
      90 minutes prior to endoscopy is safe, but milk should be discouraged because of
      suboptimal mucosal views.

PMID- 9165324
TI  - A new jumbo-channel therapeutic gastroscope for acute upper gastrointestinal
      bleeding.

PMID- 9165325
TI  - Analysis of the depressed area of small flat depressed-type colorectal tumors as
      a marker of malignant potential.

PMID- 9165326
TI  - Laparoscopic microwave coagulation therapy for solitary hepatocellular carcinoma
      performed under laparoscopic ultrasonography.

PMID- 9165327
TI  - Esophageal varices obliterated by photodynamic therapy for coexisting early
      esophageal carcinoma.

PMID- 9165329
TI  - Intrarectal fibrin glue: a novel method of hemostasis for bleeding from rectal
      tumor.

PMID- 9165328
TI  - Endoscopic polypectomy under laparotomy throughout the alimentary tract for a
      patient with blue rubber bleb nevus syndrome.

PMID- 9165330
TI  - Resolution of anorectal incontinence in herpes proctitis confirmed by anorectal
      manometry.

PMID- 9165331
TI  - Melanosis jejuni.

PMID- 9165332
TI  - An impacted metallic clip at the ampulla causing ascending cholangitis.

PMID- 9165333
TI  - Pneumatic dilation for achalasia: are all complications revealed?

PMID- 9165334
TI  - Esophageal self-expandable metallic stents.

PMID- 9165335
TI  - Pneumatic perforation of the ileum.

PMID- 9165336
TI  - Diagnostic laparoscopy: is it "safe" in the hands of our surgical colleagues?

PMID- 9165337
TI  - Wire-guided esophageal intubation with a multiband ligator attached to the end of
      the gastroscope.

PMID- 9165338
TI  - Division of the sphincter of Oddi for treatment of dysfunction associated with
      recurrent pancreatitis.

PMID- 9165339
TI  - Prospective comparison of nasal versus oral insertion of a thin video endoscope
      in healthy volunteers.

PMID- 9165340
TI  - Gabexate for the prevention of pancreatic damage related to endoscopic retrograde
      cholangiopancreatography.

PMID- 9165341
TI  - Molecular and clinical implications of loop diuretic ototoxicity.
AB  - Recent advances in molecular biology have been applied to inner ear research.
      Loop diuretic ototoxicity has been suggested, but not proven, to share a common
      mechanism with diuretic effects on renal tubules. The discovery of the molecular
      nature of the Na-K-2Cl cotransporter in the cochlea provided a better
      understanding of loop diuretic ototoxicity. In this review, we describe clinical
      reports of loop diuretic ototoxicity and other information obtained by
      physiological, biochemical and morphological investigations related to the
      mechanism sensitive to loop diuretics. Based on recent evidence for the molecular
      nature of the Na-K-2Cl cotransporter expressed in the mammalian cochlea, the
      underlying mechanisms of ototoxicity induced by loop diuretics are described.

PMID- 9165342
TI  - Anatomy of the normal human cochlear aqueduct with functional implications.
AB  - There is great variation in published descriptions of the shape, size, and
      patency of the human cochlear aqueduct. The first part of this paper describes
      the anatomy of the normal human cochlear aqueduct as determined from a study of
      101 temporal bones. Nineteen bones aged 0-1 years and approximately 10 bones per
      decade of life until age 100 years were examined. The aqueduct was found to have
      a funnel shaped aperture at the cranial end with a dural sheath extending into it
      for a varying distance. The rest of the aqueduct was filled with a meshwork of
      loose connective tissue, often with a central lumen within it. Four types of
      patencies were noted: central lumen patent throughout length of aqueduct (34%),
      lumen filled with loose connective tissue (59%), lumen occluded by bone (4%), and
      obliteration of the aqueduct (3%). The mean value (+/- SD) of the narrowest
      portion was 138 (+/- 58) microns which occurred 200-300 microns from the cochlear
      end of the aqueduct. There was no correlation between age and narrowest diameter,
      or between age and category of patency. In the second part of this paper, we
      propose quantitative models of aqueduct function, based on measurements of ductal
      dimensions and known acoustical properties of the inner ear. Our model analyses
      suggest that in normal ears, the aqueduct (1) cannot support fluid flows large
      enough to explain stapedectomy gushers, (2) does filter out cardiac- and
      respiration-induced pulses in CSF and prevents them from affecting cochlear
      function, and (3) has little effect on normal ossicular transmission of sound for
      frequencies above 20 Hz. In pathological ears, such as those with ossicular
      disruption or after a type IV tympanoplasty, a patent aqueduct might affect
      hearing for frequencies below 150 Hz.

PMID- 9165343
TI  - Postnatal expression of the alpha-thyroid hormone receptor in the rat cochlea.
AB  - Thyroid hormone receptors belong to the superfamily of nuclear receptors which
      are expressed in many tissues. Reduced levels of thyroid hormones in acquired or
      congenital hypothyroidism can lead to hearing loss which may be irreversible. In
      this study we investigated immunohistochemically the postnatal distribution of
      the triiodothyronine alpha receptor in the rat cochlea. Cell regions of high
      sensitivity towards thyroid hormones should have a high density of thyroid
      hormone receptors. Strong immunoreactivity for the alpha-thyroid hormone receptor
      was observed in spiral ganglion cells as well as inner and outer hair cells of
      the cochlea. Staining could be detected during all stages investigated from the
      first postnatal day up to day 30 and exhibited mainly a nuclear pattern. These
      observations suggest that spiral ganglion cells and hair cells are target regions
      of thyroid hormones in the adult and developing cochlea. Thyroid hormones could
      thus play an important role in the maturation of the inner ear.

PMID- 9165344
TI  - Longitudinal endolymph flow associated with acute volume increase in the guinea
      pig cochlea.
AB  - Endolymph volume disturbances were induced by microinjections of artificial
      endolymph into the second turn of the guinea pig cochlea at rates less than 60
      nl/min. Induced longitudinal movements and area changes of endolymph were
      quantified in the basal turn using an ionic flow marker technique.
      Tetramethylammonium (TMA) was used as a flow marker by iontophoresing it into
      endolymph in micromolar amounts. TMA movements in the apical and basal directions
      were monitored by ion-selective electrodes. Changes in endolymph flow and cross
      sectional area of scala media were derived using a mathematical model to
      interpret the recorded tracer time courses. The model was validated by performing
      comparable volume injections and flow measurements in fine-diameter plastic
      tubes. The rate of flow of endolymph measured prior to injection was close to
      zero, in agreement with prior studies. Based on the injection of different
      volumes into endolymph over a 15 min period, we found that injection of up to 80
      nl of artificial endolymph into the second turn would not induce flow in the
      basal turn. However, above this amount, flow towards the base increased at a rate
      which correlated with the injected volume, with endolymph moving basally by a
      distance of 0.0067 mm/nl of artificial endolymph injected. Flow rates measured in
      the third turn, on the apical side of the injection were far lower and showed
      characteristics consistent with there being no outlet at the apex. These results
      suggest that small volume disturbances are corrected locally in the cochlea, but
      larger disturbances produce a longitudinal flow of endolymph out of the cochlea
      which represents a significant mechanism contributing to homeostasis. It can be
      concluded that structures outside the cochlea, such as the endolymphatic sac, do
      play a role in the correction of endolymph volume disturbances. Although the
      maintenance of endolymph composition is dominated by local ion transport
      mechanisms, the capacity of these local mechanisms to maintain normal endolymph
      volume appears to be limited.

PMID- 9165345
TI  - Reverse middle-ear transfer function in the guinea pig measured with cubic
      difference tones.
AB  - Otoacoustic emissions are increasingly useful for determining cochlear function
      noninvasively. It is widely agreed that these acoustic signals reflect
      micromechanical processes in the cochlea. However, their quantitative
      interpretation requires knowledge of the ways in which vibrations travelling back
      to the ear canal from the cochlea are shaped by the middle ear. An intracochlear
      source is needed to derive the reverse middle-ear transfer function (rMETF) by
      comparing pressure in the external ear canal to the corresponding pressure in
      scala vestibuli. In the present study, the rMETF was obtained in vivo in the
      guinea pig using as intracochlear sound source the cubic difference tones (CDTs)
      generated by a pair of external pure tones. With a closed ear canal and open
      bulla, the rMETF was found to be flat (-35 dB) over a broad frequency range (1.5
      8 kHz). The differences between forward and reverse METF could be explained by
      different loads acting on the middle ear network, which depends on the direction
      of signal transmission. With knowledge of the rMETF, it becomes possible to
      quantify CDTs within the cochlea by measuring them noninvasively in the ear
      canal.

PMID- 9165346
TI  - Dopamine regulates the glutamatergic inner hair cell activity in guinea pigs.
AB  - Recent immunocytochemical and biochemical studies support a possible
      neurotransmitter function of dopamine (DA) in the efferent olivocochlear
      innervation of the guinea pig cochlea. However, the physiological role of DA in
      cochlear neurotransmission remains unknown. In the present study
      microiontophoretic techniques were used for testing the action of DA as well as
      D1- and D2-agonists and -antagonists on spontaneous and N-methyl-D-aspartic acid
      (NMDA)-, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-, kainic
      acid- or glutamate-induced firing of afferent fibres in the dendritic region of
      inner hair cells. Subsynaptic spike activities of anaesthetised guinea pigs were
      recorded after exposing the third or fourth turn of the cochlea for electrode
      penetration. Application of DA alone had very little effect on the spontaneous
      afferent firing rate. In contrast, firing induced by NMDA or AMPA could be
      depressed by additional administration of DA in a dose-dependent manner. A
      similar reduction of the induced spike activity was seen after co-administration
      of D1- or D2-agonists. The action of DA on glutamate agonist-induced firing could
      be blocked by D1- as well as D2-antagonists. These results show that DA can
      depress the activated firing rate of the afferent fibres and that this action is
      mediated by both D1- and D2-receptor subtypes.

PMID- 9165347
TI  - Hair bundles of sea anemones as a model system for vertebrate hair bundles.
AB  - Sea anemones are marine invertebrates that use hair bundles to detect swimming
      movements of prey. Prey are captured by nematocysts (stinging capsules) that
      discharge into the prey. To further characterize anemone hair bundles and to
      compare hair bundles in anemones with hair bundles in vertebrates, we
      investigated fine structure and cytochemistry of anemone hair bundles. In
      addition, using a biological assay based on counting nematocysts discharged into
      vibrating test probes, we examined sensitivity of vibration detection to
      aminoglycoside antibiotics, Ca(2+)-free seawater, and amiloride. Like vertebrate
      hair bundles, anemone hair bundles are composed of stereocilia, possess lateral
      linkages between stereocilia whose preservation for transmission electron
      microscopy is enhanced by ruthenium red, and possess tip links morphologically
      similar to vertebrate tip links. Furthermore, vibration-dependent discharge of
      nematocysts is reversibly inhibited by 10(-4) M streptomycin and abolished by
      brief exposure to Ca(2+)-free seawater. However, unlike vertebrate hair bundles,
      anemone hair bundles appear to be insensitive to amiloride since vibration
      dependent discharge of nematocysts is unaffected by up to mM amiloride. Thus,
      anemone hair bundles may serve as a useful model system for vertebrate hair
      bundles with the interesting feature of being insensitive to amiloride.

PMID- 9165348
TI  - Effects of selective inner hair cell loss on auditory nerve fiber threshold,
      tuning and spontaneous and driven discharge rate.
AB  - Current theories assume that the outer hair cells (OHC) are responsible for the
      sharp tuning and exquisite sensitivity of the ear whereas inner hair cells (IHC)
      are mainly responsible for transmitting acoustic information to the central
      nervous system. To further evaluate this model, we used a single (38 mg/kg) or
      double dose (38 mg/kg, 2 times) of carboplatin to produce a moderate (20-28%) or
      severe (60-95%) IHC loss while sparing a large proportion of the OHCs. The
      surviving OHCs were functionally intact as indicated by normal cochlear
      microphonic (CM) potentials and distortion product otoacoustic emissions (DPOAE).
      Single-unit responses were recorded from auditory nerve fibers to determine the
      effects of the moderate or severe IHC loss on the output of the surviving IHCs.
      Most neurons that responded to sound in the single-dose group had normal or near
      normal thresholds and normal tuning. Relatively few neurons in the double-dose
      group responded to sound because of the severe IHC loss. The neurons that did
      respond to sound had narrow tuning curves. Some neurons in the double-dose group
      also had thresholds that were within the normal range, but most had thresholds
      that were elevated a mild-to-moderate degree. These results indicate that intact
      IHCs can retain relatively normal sensitivity and tuning despite massive IHC loss
      in surrounding regions of the cochlea. However, the spontaneous and driven
      discharge rates of neurons in the carboplatin-treated animals were significantly
      lower than normal. These changes could conceivably be due to sublethal damage to
      surviving IHCs or to postsynaptic dysfunction in the auditory nerve.

PMID- 9165349
TI  - Contralateral suppression and stimulus rate effects on evoked otoacoustic
      emissions.
AB  - Transiently evoked otoacoustic emissions (EOAE) were recorded in normal-hearing
      humans using pseudorandom pulse trains. This allowed the effect of increasing
      stimulus rate to be studied on EOAE amplitudes, input-output (I/O) functions and
      suppression by contralateral stimulation. EOAEs are very probably due to
      micromechanical properties of cochlear outer hair cells, and contralateral
      suppression is considered to result from olivo-cochlear efferent activation.
      EOAEs at various stimulus rates showed excellent reproducibility. Total EOAE
      amplitude diminished as interstimulus interval (ISI) decreased from 20 to 3 ms,
      but not for ISIs under 3 ms. The amplitude reduction was significant only on EOAE
      spectrum bands below 3.4 kHz. I/O functions, which kept a linear pattern, were
      steeper, and contralateral suppression was lower, with the highest stimulus rate
      (1111 c/s) relative to other rates. The EOAE decline with increasing stimulus
      rate might be due to incomplete recovery after adaptation of outer hair cells.
      The lower contralateral suppression at high stimulus rates suggests that crossed
      olivo-cochlear bundle action is lessened when outer hair cells are responding to
      a high-rate stimulus. An explanation may be that contralateral stimulation and a
      high-rate ipsilateral stimulus act via the same mechanisms, i.e., that high-rate
      stimulation activates an ipsilateral efferent loop.

PMID- 9165351
TI  - Compartmentalized vesicular traffic around the hair cell cuticular plate.
AB  - Through thin-section and freeze-fracture electron microscopy, we identify
      structural correlates of an intense vesicular traffic in a narrow band of
      cytoplasm around the cuticular plate of the bullfrog vestibular hair cells.
      Myriads of coated and uncoated vesicles associated with longitudinally oriented
      microtubules populate the narrow cytoplasmic region between the cuticular plate
      and the actin network of the apical junctional belt. If microtubules in the
      sensory hair cells, like those in axons, are pathways for organelle transport,
      then the characteristic distribution of microtubules around the cuticular plate
      represents transport pathways across the apical region of the hair cells. This
      compartmentalized membrane traffic system appears to support an intense vesicular
      release and uptake along a band of apical plasma membrane near the cell border.
      Functions of this transport system may include membrane recycling as well as
      exocytotic and endocytotic exchange between the hair cell cytoplasm and the
      endolymphatic compartment.

PMID- 9165350
TI  - In vivo binding and hearing loss after intracochlear infusion of KHRI-3 antibody.
AB  - The IgG1 mouse monoclonal antibody (MAb) KHRI-3, binds to an antigen of 65-68 kDa
      expressed on inner ear supporting cells in guinea pigs. We previously showed
      [Nair et al. (1995) Monoclonal antibody induced hearing loss. Hear. Res. 83, 101
      113] that mice carrying the KHRI-3 hybridoma develop high frequency hearing loss
      and loss of hair cells in the basal turn suggesting that this MAb causes immune
      mediated sensorineural hearing loss. To evaluate the specificity of this effect,
      sterile KHRI-3 and control IgG1 preparations were infused directly into the
      guinea pig cochlea using Alzet mini-osmotic pumps. Assessments included: (1)
      hearing, measured by click auditory brain stem responses (ABRs); (2) in vivo
      antibody binding; and (3) the structural integrity of the organ of Corti. Nine
      animals were infused with KHRI-3 preparations and 5 controls were infused with
      control IgG1. Four guinea pigs given KHRI-3 developed 25-55 dB hearing loss.
      Control animals showed no difference from baseline. In vivo binding of KHRI-3 was
      detected in the organ of Corti in 6 of the 9 animals, including all 4 that had
      hearing loss. No staining was observed with control antibody. Confocal microscopy
      revealed that the in vivo KHRI-3 antibody binding pattern was identical to that
      obtained by incubating fixed tissue in vitro with KHRI-3. Histologic examination
      revealed an increased frequency of hair cell loss in KHRI-3 treated ears when
      compared to either the contralateral ears of the same guinea pigs or the IgG1
      treated ears of control animals. The lesions in the infused ears of guinea pigs
      were scattered throughout the cochlea from base to apex. These experiments
      demonstrate the following points: (1) Antibodies can be chronically infused
      directly into the cochlea of living animals. (2) The KHRI-3 antibody binds to
      live supporting cells within the organ of Corti. (3) Infusion of an inner ear
      specific antibody affects auditory function. (4) The infusion of irrelevant
      antibody had no effect on the structure or function of the ear. This system
      provides an animal model for further studies of antibody-induced sensorineural
      hearing loss.

PMID- 9165352
TI  - Age-related changes in GFAP-immunoreactive astrocytes in the rat ventral cochlear
      nucleus.
AB  - The age-related changes in the ventral cochlear nucleus (VCN) as revealed by
      glial fibrillary acid protein (GFAP) immunoreactivity were analyzed in the
      following age groups: 3-, 6-, 12-, 18-, and 24-month-old Sprague-Dawley rats. A
      cartographic and a quantitative analysis showed a significant increase in the
      number of GFAP positive astrocytes during the first year of life and a
      significant decrease in older rats. We also observed an age-induced modification
      in the spatial distribution of GFAP positive astrocyte. In the anterior part of
      the VCN of the 3- and 6-month-old rats, we observed a significant decrease in the
      rostro-caudal as well in the dorso-ventral axes. In the posterior part of the
      VCN, a significant decrease in the dorso-ventral axis could be also observed, but
      no significant difference in the spatial distribution was obtained in the rostro
      caudal axis. In older rats, the distribution appeared homogeneous throughout the
      nucleus. Additionally, aging was associated with a significant increase in GFAP
      positive astrocyte sizes, except for immunolabelled astrocytes in the granule
      cell layer. The different levels of GFAP expression occurring in the VCN during
      normal aging could reflect a progressive decline of cellular activity in the VCN,
      without severe cell degeneration or synaptic loss.

PMID- 9165353
TI  - Fine structure of extracellular matrix and basal laminae in two types of abnormal
      collagen production: L-proline analog-treated otocyst cultures and
      disproportionate micromelia (Dmm/Dmm) mutants.
AB  - L-Azetidine-2-carboxylic acid (LACA), a naturally occurring vegetable imino acid,
      can be incorporated into mammalian proteins in place of proline, thereby
      eliciting an inhibitory effect on collagen secretion. Exposure of explants of the
      embryonic mouse inner ear to LACA reduces the number of collagen fibrils in the
      otic capsule, gives rise to a dose-dependent derangement of the basal lamina, and
      ultimately results in dysmorphogenesis and retarded differentiation of the inner
      ear. Disproportionate micromelia (Dmm) is an incomplete dominant form of dwarfism
      characterized by a reduced quantity of type II collagen in the cartilaginous
      extracellular matrix (ECM). Abnormal morphogenesis in homozygotic Dmm mice
      resembles the abnormal morphogenesis observed in LACA-exposed otic explants,
      resulting in malformed inner ears with a bulky cartilaginous capsule and a lack
      or reduction of defined perilymphatic spaces (Van De Water and Galinovic
      Schwartz, 1987). In this study, we examined by ultrastructural analysis LACA
      exposed otic explants and inner ears of Dmm/Dmm mouse embryos for abnormalities
      in the collagenous constituents of the basal laminae and capsular ECM. We
      demonstrate, in comparison to normal embryonic mouse inner ears, a reduction in
      collagen fibrils and irregular cytodifferentiation of chondrocytes in the ECM of
      LACA-exposed and Dmm/Dmm inner ears as well as in the basal laminae of LACA
      exposed specimens. In addition, we provide evidence of dysmorphogenesis of the
      otic capsule and perilymphatic spaces in LACA-exposed explants. Moreover, while
      previous studies demonstrated the anomalous development of sensory structures in
      otocyst explants following LACA exposure, in this study we provide evidence of
      the normal morphogenesis of otic epithelial-derived sensory structures in
      homozygotic Dmm/Dmm mouse embryos.

PMID- 9165354
TI  - Differences between guinea pig and rat in the dorsal cochlear nucleus: expression
      of calcium-binding proteins by cartwheel and Purkinje-like cells.
AB  - This study describes differences between guinea pig and rat in the
      immunoreactivities for calbindin (CB-IR) and parvalbumin (PV-IR) in cartwheel
      (CWC) and Purkinje-like (PLC) cells of the dorsal cochlear nucleus (DCN). CWCs
      are the most important inhibitory interneurons of the DCN. Their soma and
      dendrites stain intensely for CB-IR in guinea pigs but only weakly and
      incompletely in rats. In both species, the CWCs do not show PV-IR. PLCs, a rare
      type of DCN cells often interpreted as displaced cerebellar Purkinje cells
      misrouted during migration, are known from rat and mouse and are here described
      for guinea pig DCN. PLCs are intensely and completely stained for CB-IR and PV-IR
      in guinea pigs. In rats, they stain with similar completeness only for CB-IR, PV
      IR being weak and restricted to the cell's soma. Similar staining differences
      between the two species are seen with the cerebellar Purkinje cells, i.e., PLCs
      resemble the cerebellar Purkinje cells more than do the CWCs. Based on the
      present material (and preliminary findings in a primate (marmoset), we speculate
      that the PLCs have their place in the circuitry of the DCN receiving input via
      parallel fibers, like the CWCs, and possibly projecting their axon onto the
      cerebellum.

PMID- 9165355
TI  - The influence of the cochlear efferent system on chronic acoustic trauma.
AB  - The role of the olivocochlear bundle (OCB) in modulating noise-induced permanent
      injury to the auditory periphery was studied by completely sectioning the OCB
      fibers in chinchillas and exposing the animals while awake to a broad-band noise
      at 105 dB SPL for 6 h. Outer hair cell (OHC) function was assessed by measuring
      2f1-f2 distortion product otoacoustic emissions (DPOAE) at frequencies from 1.2
      to 9.6 kHz and cochlear microphonics (CM) at frequencies from 1 to 8 kHz. As a
      result of de-efferentation, the CM was decreased but the DPOAEs were unchanged in
      de-efferented ears as compared with efferented control and sham-operated ears.
      Following noise exposure, the ears that were de-efferented showed significantly
      more depression of DPOAE input/output functions and greater decrement of CM
      amplitude. The differences between de-efferented and efferent-innervated ears
      were evident across all the frequencies. The cochlear lesions of the OHCs
      reflected by traditional cytocochleograms, however, were minimal in both
      efferented and de-efferented ears. The results indicate that cochlear de
      efferentation decreases the CM in chinchilla and increases the ear's
      susceptibility to noise-induced permanent hearing damage. More importantly, de
      efferentation increases susceptibility at low frequencies as well as high
      frequencies.

PMID- 9165356
TI  - Prevention of venous thromboembolism. International Consensus Statement
      (guidelines according to scientific evidence).

PMID- 9165357
TI  - A prospective follow-up study of acute deep venous thrombosis using colour duplex
      ultrasound, phlebography and venous occlusion plethysmography.
AB  - OBJECTIVE: To study the extent of deep venous thrombosis (DVT) and thrombus
      regression over time and to compare the results obtained with different
      diagnostic techniques. EXPERIMENTAL DESIGN: A prospective follow-up study with
      repeated examinations during a 6-month period. SETTING: Patients studied at
      clinical vascular laboratories. PATIENTS: Forty patients hospitalised for acute
      DVT. Thirty-six of these completed the follow-up period. MEASURES: The diagnosis
      of DVT was confirmed with phlebographic and/or ultrasonographic techniques. The
      patient were then re-examined with colour duplex ultrasound and venous occlusion
      plethysmography after one week, 3 months and 6 months and with phlebography after
      1 week and 6 months. The extent of DVT and number of occluded segments were
      determined with phlebographic and ultrasonographic techniques. Venous occlusion
      plethysmography was used to evaluate the functional degree of outflow
      obstruction. RESULTS: Colour duplex scanning at 3 months' and 6 months' follow-up
      showed that 55% and 74% of initially occlusive thrombi, respectively, were
      recanalized, with thrombus resolution occurring faster and more completely in
      those initially limited to popliteal and/or calf level. Discrepancies between
      phlebography and duplex scanning were found in 6% (26/441) of venous segments
      investigated by both methods, primarily concerning flow in the veins below the
      knee. CONCLUSIONS: In comparison with phlebography, colour duplex scanning is an
      accurate method for evaluation and follow-up of patients with DVT. The non
      invasive nature of colour duplex scanning makes this method extremely suitable
      for repeated studies and thus a potentially very valuable tool for both clinical
      and research studies of circulatory changes involved in acute and chronic DVT.

PMID- 9165358
TI  - Natural history of proximal deep vein thrombosis assessed by duplex ultrasound.
AB  - BACKGROUND: The late sequelae of an acute deep vein thrombosis (DVT) are
      difficult to predict. There are many retrospective studies which suggest that the
      post-phlebitic syndrome is associated with the development of valvular
      incompetence but these have lead to little understanding of the changes involved
      in the venous system following an acute thrombotic event. Duplex ultrasound
      imaging is an useful method to study changes in the venous system because it can
      locate a thrombus, assess the changes which occur over time and monitor the
      development of recanalization and reflux of blood flow. METHODS: In this study,
      50 patients were followed by serial duplex ultrasound examination to determine if
      a more accurate prediction of patients at risk could be found. Rapid thrombolysis
      and extent of the thrombosis are both factors which influence the return of the
      vein to normal function. RESULTS: Complete thrombolysis within a short period of
      time occurred in 24% of patients resulting in preserved valvular function. After
      one year there were 34% with early post-phlebitic symptoms. All of these patients
      had veins which recanalized slowly and developed valvular incompetence with
      reflux. Veins remained occluded in 14% of patients and of these 8% had competent
      collateral channels. This appeared to be a better outcome because none of these
      patients had developed symptoms after one year. Recurrent DVT's occurred in 8%
      within the year. Of these, 4% presented with symptoms and 4% were without
      symptoms but thrombus was found by ultrasound examination. CONCLUSIONS: Serial
      duplex examination leads to better understanding of the natural history of an
      acute DVT. This may have clinical implications and lead to better management of
      acute DVT thereby reducing the long term risks of the post phlebitic limb.

PMID- 9165360
TI  - Inflammatory response to aorto-bifemoral graft surgery.
AB  - OBJECTIVE: To evaluate the systemic release of major cytokines and complemental
      activation during elective aorto-bifemoral bypass surgery and the influence on
      the postoperative course. DESIGN: Prospective randomised study. SETTING:
      University hospital, Sweden. PATIENTS: Fourteen consecutive patients with aorto
      iliac occlusive disease were randomised to receive either a bifurcated e PTFE
      graft with stretch properties or a collagen coated Dacron graft. MAIN OUTCOME
      MEASURES: Immunologic parameters were assessed and included the cytokines TNF
      alpha (tumor necrosis factor), IL-6, IL-8, S-IL-2R and complemental factor C5a.
      Furthermore, acute plasma proteins, including C-reactive protein, and the
      different white blood cell fractions were determined. Sampling was performed
      frequently during surgery and postoperatively up to one month. RESULTS: An
      increase of serum-TNF alpha levels was observed early after declamping. This
      response preceded an increase of IL-6 levels and of C-reactive protein. No
      release of IL-8 was identified. A significant correlation between TNF alpha, IL-6
      and C-reactive protein was observed (p < 0.001). A positive correlation was also
      observed for the degree of surgical trauma (blood loss). No significant
      differences between the two graft materials were encountered. The complemental
      system was also involved in the acute reactions and a marked increase of C5a
      levels was noted. A decrease of S-IL-2R levels as well as lymphocyte
      concentrations was also observed postoperatively and was interpreted as a
      downregulation of the immune-system in the immediate postoperative course.
      CONCLUSIONS: The results demonstrate an early and generalized inflammatory
      response during and after aortic surgery with involvement of different cytokines
      as well as the complemental system. TNF alpha appears to play a central role in
      the release of other cytokines, but IL-6 seemed to correlate best with later
      development of nonvascular complications. Few differences were found between the
      different grafts and the response seems to be influenced by other factors such as
      the surgical procedure and ischaemia/reperfusion injury.

PMID- 9165359
TI  - The ultrasonic evaluation of the carotid intima-media thickness and its relation
      to risk factors of atherosclerosis in normal and diabetic population.
AB  - High-resolution ultrasound provides an excellent tool for the non-invasive
      assessment of the severity of atherosclerosis. It allows the measurement of the
      common carotid artery (CCA) intima media thickness (IMT) which has been found to
      be a feasible and reliable method for the evaluation of the progression and
      regression of the disease. The aim of this study was to evaluate the influence of
      risk factors of atherosclerosis on the mean CCA IMT in both normal and non
      insulin dependent diabetic (NIDDM) individuals and to determine the effect of
      diabetes as a major atherosclerotic risk factor on the CCA IMT. Four hundred and
      eighty-four subjects were studied, 244 normal individuals and 240 non insulin
      dependent diabetic patients. The right and left CCA IMT were measured using high
      resolution ultrasonography. Both in the normal and diabetic individuals, the mean
      CCA IMT was found to increase linearly with age (p < 0.01), was directly related
      to total serum cholesterol and triglyceride and inversely related to HDL
      cholesterol (p < 0.01). Multiple linear regression analysis showed the most
      important risk factor influencing the CCA IMT and hence early athrosclerosis to
      be the presence of diabetes, followed by serum HDL-cholesterol (inverse
      relation), total cholesterol, age and serum triglyceride. This study has shown
      that high resolution ultrasonography can be used to evaluate the effect to risk
      factors on early atherosclerosis and could be used to monitor future clinical
      trails aiming to modify the progression of atherosclerosis in the population.

PMID- 9165361
TI  - Incidence of deep vein thrombosis following vascular surgery.
AB  - OBJECTIVE: The incidence of deep vein thrombosis (DVT) has been well documented
      in general and orthopaedic surgery but there have been few reports of the
      incidence of DVT following vascular surgery. Our aim was to perform a prospective
      study of the incidence of DVT in patients managed on the Vascular Unit at our
      institution. EXPERIMENTAL DESIGN: One hundred and forty two consecutive patients
      presenting for repair of abdominal aortic aneurysm, reconstruction of lower
      extremity arterial occlusive disease or amputation were studied. Venous duplex
      ultrasound examination was performed preoperatively and between day seven to 10
      postoperatively. All patients received standard DVT prophylaxis of 5,000 units of
      unfractionated heparin subcutaneously three times daily and intraoperative
      sequential compression devices. RESULTS: Fourteen patients (9.8%) were found to
      have postoperative DVT with one patient (0.7%) having a documented pulmonary
      embolism. The incidence of DVT following reconstructive surgery was 9.1% and
      14.3% following amputation. CONCLUSIONS: In patients having vascular
      reconstructive surgery and, in particular, amputation, there is still a moderate
      risk of DVT despite the application of standard prophylactic measures. There may
      be a role for newer modalities of prophylaxis such as low molecular weight
      heparin especially in the higher risk amputation group.

PMID- 9165362
TI  - Cholesterol embolisation. A lethal complication of instrumentation of an
      aneurysmal aorta: a case report.
AB  - A case of cholesterol embolisation (CE) following instrumentation of an
      aneurysmal aorta is presented. The patient developed myalgias, livedo reticularis
      in the buttocks, suprapubic area and legs, that progressed to patchy gangrene and
      renal failure. Maximum conservative management including heparin, iloprost and
      haemodialysis was ineffective, in keeping with previous reports that there is no
      known therapy for CE. The aetiology, presentation, treatment and prognosis of
      this condition is discussed. With the ever increasing use of endovascular
      treatment of abdominal aortic aneurysms, this complication may be more frequently
      encountered.

PMID- 9165363
TI  - Paradoxical embolism and aortic occlusion: a case report.
AB  - This is the case report of a 45-year-old woman who sustained a left popliteal
      artery embolism. Ten days after popliteal embolectomy, she developed sudden
      occlusion of the distal aorta. She required a bifemoral embolectomy.
      Transesophageal echocardiogram demonstrated an atrial septal aneurysm and a
      septal defect with a right to left shunt. A venogram showed deep venous
      thrombosis in the right leg as the potential source of the embolism. Paradoxical
      embolization should be considered when ever an unexplained arterial occlusion
      occurs, especially in younger patients.

PMID- 9165364
TI  - Application of physiologically active substances isolated from natural resources
      to pharmacological studies.
AB  - Numerous neurotoxins that alter Na(+)-channel function have been shown to be
      useful tools for characterizing Na+ channels. Polypeptide blockers of voltage
      dependent K+ channels (dendrotoxins, etc.) and Ca(2+)-activated K+ channels
      (apamine, etc.) have been studied extensively by numerous investigators. Peptide
      toxins, calciseptine and omega-conotoxins have been attracting much attention as
      inhibitors of L-type and N-type Ca2+ channels, respectively, while omega
      conotoxins-MVIIC and omega-agatoxin IVA have been used as new types of Ca(2+)
      channel blockers. Ryanodine and bromoeudistomin D analogues have been extensively
      used to elucidate Ca(2+)-release-channel functions and to purify its target
      protein. Polypeptide toxins (myotoxin alpha, etc.) and macrolides (FK 506, etc.)
      are useful Ca2+ releasers with a novel mechanism, while natural products such as
      thapsigargin and gingerol have been used as modulators of Ca(2+)-pumping ATPase.
      Some modulators of the function of myosin (purealin, etc.) and actin (goniodomin
      A, etc.) have been demonstrated to be important chemical probes for understanding
      the physiological roles of the contractile proteins in structural changes and
      their interaction in muscle contraction. A large number of protein kinase
      inhibitors (staurosporine, etc.) and phosphatase inhibitors (okadaic acid, etc.)
      are widely used as first-choice reagents for studying protein phosphorylation.
      These natural products have become essential tools for studying the regulatory
      mechanism of cellular ion movements, muscle contraction and protein
      phosphorylation.

PMID- 9165365
TI  - Studies on the novel antiallergic agent HSR-609: its penetration into the central
      nervous system in mice and guinea pigs and its selectivity for the histamine H1
      receptor.
AB  - We studied the pharmacological characteristics of HSR-609 (3-[4-(8-fluoro-5,11
      dihydrobenz[b]oxepino[4,3-b]pyridin-11- ylidene)- piperidino]propionic acid
      dihydrate), a novel amphoteric antiallergic agent, on the central nervous system
      (CNS). Its selectivity for the histamine H1-receptor and its ability to penetrate
      into the CNS were compared with those of typical antiallergic agents and the
      nonamphoteric basic compound PY-608 (8-fluoro-5,11-dihydro-11-(1-methyl-4
      piperidylidene)benz[b]oxe pino- [4,3-b]pyridine), which has a chemical structure
      similar to that of HSR-609. In the in vitro study, HSR-609 had a high affinity
      for H1-receptors in the guinea pig cerebral cortex in comparison to affinities
      for muscarinic and serotonin 5-HT2-receptors in the rat cerebral cortex, while
      the selectivity of PY-608 for the H1-receptor was low. The inhibitory effects of
      these antiallergic agents on histamine-induced increase of vascular permeability
      in mice (ED50) were compared with the displacement of [3H]mepyramine binding to
      H1-receptors in mouse brain ex vivo (ID50). The ID50/ED50 ratio of HSR-609 was
      much larger than those of cyproheptadine, ketotifen and PY-608 and larger than
      those of terfenadine and cetirizine. HSR-609 was found to display selective
      displacement of the [3H]mepyramine binding to H1-receptors for lung vs cerebral
      cortex as found with terfenadine in guinea pigs ex vivo. These findings suggest
      that HSR-609 has high selectivity for the H1-receptor and poor ability to
      penetrate into the CNS in mice and guinea pigs due to its amphoteric chemical
      structure.

PMID- 9165366
TI  - New ulcerative colitis model induced by sulfhydryl blockers in rats and the
      effects of antiinflammatory drugs on the colitis.
AB  - We tried to produce a new ulcerative colitis model in rats by topical
      administration of sulfhydryl blockers. After male SD rats were fasted for 24 hr,
      100 microliters of 3% N-ethylmaleimide (NEM) or iodoacetamide (IA) was introduced
      into the colon via a Nelaton's catheter. Both NEM and IA caused severe diarrhea
      with rectal bleeding and decreased body weight for about 7 days. At autopsy,
      adhesions and dilatation of the colon and severe mucosal lesions were observed.
      Both the weight and myeloperoxidase activity of the colon increased markedly.
      Maximum changes were observed within 1-3 days followed by gradual recovery, but
      even on day 21, some abnormalities were still observed. The ulceration and
      inflammation of the colon were confirmed by histological studies.
      Antiinflammatory drugs such as indomethacin inhibited the inflammation of the
      colon by NEM, but aggravated the ulceration. These results revealed that
      sulfhydryl blockers instilled into the colon caused ulcerative colitis in the
      rat. This model may be useful in studies on the pathogenesis of ulcerative
      colitis and the evaluation of drugs for therapy. Furthermore, it was suggested
      that antiinflammatory drugs may delay the healing of colonic ulcers.

PMID- 9165367
TI  - Muscarinic acetylcholine receptors on rat thymocytes: their possible involvement
      in DNA fragmentation.
AB  - Several studies have shown that the nervous (and hormonal) system controls immune
      functions. In the present study, we examined the presence of muscarinic
      acetylcholine receptors and the effect of carbachol on DNA fragmentation in adult
      rat thymocytes. Rat thymocytes possessed high affinity binding sites for the
      muscarinic antagonist [3H]3-quinuclidinyl benzilate (QNB). The average number of
      binding sites per cells was 3000, and the equilibrium dissociation constant of
      [3H]QNB on intact cell was approximately 80 nM. The binding was inhibited by an
      M1- and M3-selective antagonist, 4-diphenylacetoxy-N-methylpiperidine methiodine
      (4-DAMP). Hydrocortisone (100 mg/kg, s.c.) treatment of rats for 2 days prior to
      sacrifice increased the average number of [3H]QNB binding sites on thymocytes by
      82 +/- 33%. The gel electrophoresis of DNA extracted from carbachol-treated
      thymocytes revealed a ladder pattern typical of intranucleosomal fragmentation.
      The addition of oxotremorine-M also induced DNA fragmentation and the effects of
      muscarinic agonists were inhibited by the addition of atropine or 4-DAMP. The
      results suggest the existence of muscarinic receptors and the possible
      involvement in apoptosis in thymocytes.

PMID- 9165368
TI  - Cerebroprotective effects of a novel pyrazoline derivative, MS-153, on focal
      ischemia in rats.
AB  - MS-153 ((R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline) is a novel pyrazoline
      compound that has potent cerebroprotective effects in the rat focal cerebral
      ischemia model. Middle cerebral artery (MCA) occlusion in rats allows detailed
      assessment of both functional and morphological sequelae of brain infarct. Using
      this model, we evaluated the cerebroprotective effects of MS-153. Treatment with
      MS-153 (12.5 mg/kg, i.v. bolus followed by 6.25 mg/kg/hr or 25.0 mg/kg, i.v.
      bolus followed by 12.5 mg/kg/hr infusion for 7 days) significantly reduced
      infarct volumes and improved neurological deficits in MCA occluded rats 7 days
      after occlusion. Delayed treatment significantly reduced infarct volume 24 hr
      after MCA occlusion when MS-153 (25.0 mg/kg, i.v. bolus followed by 12.5 mg/kg/hr
      infusion for 21 hr) administration was started 3 hr after occlusion. Brain edema
      was also significantly improved when MS-153 (25.0 mg/kg, i.v. bolus followed by
      12.5 mg/kg/hr infusion for 18 hr) administration was started 6 hr after
      occlusion.

PMID- 9165369
TI  - Relationship between desensitization and downregulation of beta-adrenoceptors in
      cardiac tissues after prolonged in vivo infusion of T-0509, a beta 1-adrenoceptor
      agonist.
AB  - To examine the contribution of beta-adrenoceptor (beta AR) downregulation to
      desensitization of beta ARs by chronic administration of a beta AR agonist, we
      compared the adenylyl cyclase (AC) activities in two kinds of cardiac ventricular
      membranes with decreased available beta ARs: one was derived from rats infused
      with a selective beta 1 AR agonist, T-0509 [(-)-(R)-1-(3,4-dihydroxyphenyl)- 2
      [(3,4-dimethoxyphenethyl)-amino]ethanol hydrochloride], in vivo (40
      micrograms/kg/hr, s.c. for 6 days); and the other was obtained from treatment of
      control membranes with an irreversible beta AR antagonist, bromoacetyl alprenolol
      methane (BAAM). T-0509 infusion decreased the densities of beta 1 ARs and beta 2
      ARs by 26% and 32%, respectively, and reduced the maximal isoproterenol
      stimulated AC activity by 53%. The amount of Gs alpha and Gi alpha proteins in
      the membranes was not significantly changed by T-0509 infusion. To make
      preparations that mimic the T-0509-induced downregulation, we treated the control
      membranes with 100 nM BAAM in vitro. The BAAM treatment decreased the Bmax value
      of [125I]iodocyanopindolol for beta 1 ARs and beta 2 ARs by 29% and 36%,
      respectively, whereas it reduced the maximal effect of isoproterenol on AC
      activity only by 37%. These results suggest that downregulation of beta ARs
      cannot fully account for the desensitization by chronic treatment of T-0509 and
      that other mechanism(s) can play a significant role in the loss of
      responsiveness.

PMID- 9165370
TI  - Enhancement of interleukin-1 alpha mediated autocrine growth of cultured human
      keratinocytes by sho-saiko-to.
AB  - We investigated the effects of Sho-saiko-to, the most commonly used herbal
      medicine in Japan, on the production of interleukin (IL)-1 alpha by cultured
      human epidermal keratinocytes. IL-1 alpha production was significantly promoted
      by treatment with 100 or 500 micrograms/ml Sho-saiko-to for 24 or 48 hr.
      Expression of IL-1 alpha receptors was the most markedly upregulated after
      treatment with 500 micrograms/ml Sho-saiko-to for 24 hr and with 100 or 500
      micrograms/ml for 48 hr; these cells showed the characteristics of multilayered
      differentiated keratinocytes. The presence of an anti-IL-1 alpha antibody during
      the treatment with 500 micrograms/ml of Sho-saiko-to for 24 or 48 hr or with 100
      micrograms/ml for 48 hr significantly down-regulated the synthesis by the
      keratinocytes and induced damages in them. Keratinocytes treated with Sho-saiko
      to might produce IL-1 alpha and express IL-1 alpha receptors. IL-1 alpha may
      regulate the proliferation and differentiation of keratinocytes after Sho-saiko
      to treatment. These findings suggest that Sho-saiko-to enhances the autocrine
      growth mediated by IL-1 alpha.

PMID- 9165371
TI  - Dual effects of lisinopril on puromycin aminonucleoside nephrosis in unilaterally
      nephrectomized rats.
AB  - The therapeutic effects of angiotensin converting enzyme inhibitor, lisinopril,
      on puromycin aminonucleoside (PAN)-induced nephrosis were investigated using
      unilaterally nephrectomized rats. Lisinopril showed potent dual effects on PAN
      nephrosis. Lisinopril treatment (50 mg/l in drinking water) from day 5 or day 9
      reduced urinary protein excretion and suppressed the development of glomerular
      sclerosis at 8 weeks after PAN injection (150 mg/kg, i.p.), indicating a
      therapeutic effect on the nephrosis. Recovery of decreased anionic charge sites
      on the glomerular basement membrane was involved, at least in part, in the
      therapeutic action of lisinopril against proteinuria. On the other hand, oliguria
      and progressive azotemia derived from continuous deterioration of the renal
      function was induced if the treatment of lisinopril was started on the same day
      as PAN injection. The renal dysfunction induced by simultaneous administration of
      lisinopril with PAN could be abolished by combination dosing with sarcosine, an
      angiotensin II (AII)-receptor agonist. These results indicate that lisinopril
      treatment attenuates proteinuria by ameliorating the anionic charge barrier on
      the glomerular basement membrane and that it also protects against the
      development of chronic renal disease with segmental glomerular sclerosis,
      although AII depletion during the acute nephrotic stage exacerbates the renal
      damage in PAN nephrosis of unilaterally nephrectomized rats.

PMID- 9165373
TI  - Effect of Japanese angelica root extract on pentobarbital-induced sleep in group
      housed and socially isolated mice: evidence for the central action.
AB  - We investigated the effect of the aqueous extract of Japanese angelica root (JAR)
      on pentobarbital (PB) sleep in group-housed and socially isolated mice. The JAR
      extract (1.25-2.5 g/kg, p.o.) dose-dependently reversed the decrease in PB sleep
      caused by isolation stress without affecting PB sleep in group-housed mice. The
      JAR extract (2.5 g/kg, p.o.) also antagonized the decrease in PB sleep caused by
      the alpha 2-adrenoceptor antagonists yohimbine and idazoxan (1 mg/kg, i.p.) and
      the alpha 1-adrenoceptor agonist methoxamine (200 nmol, i.c.v.) in group-housed
      mice. These results suggest that the JAR extract reverses changes in the arousal
      level caused by isolation stress and the activation of central noradrenergic
      systems.

PMID- 9165372
TI  - Phorbol 12-myristate 13-acetate (PMA)-induced oxyradical production in rheumatoid
      synovial cells.
AB  - We successfully detected the oxyradical production in human synovial A
      (macrophage-like) and B (fibroblast-like) cells by phorbol 12-myristate 13
      acetate (PMA) using the luminol-chemiluminescence method. The PMA (0.1
      microgram/ml)-induced photon generation was abolished by an O2- scavenger,
      superoxide dismutase, and an H2O2 scavenger, catalase, suggesting that the
      stimulus produced oxyradicals in synovial cells. Both of these responses were
      abolished by a protein kinase C (PKC) inhibitor, calphostine C, but unaffected by
      an intracellular Ca2+ chelator, BAPTA-AM, and Ca2+ removal from the extracellular
      medium. These findings suggest that synovial A and B cells produce oxyradicals
      through PKC-mediated and [Ca2+]i-independent mechanisms, probably through the
      activation of NADPH oxidase.

PMID- 9165374
TI  - High affinity binding of azasetron hydrochloride to 5-hydroxytryptamine3
      receptors in the small intestine of rats.
AB  - The binding affinity of azasetron hydrochloride (azasetron) for the 5
      hydroxytryptamine3 (5-HT3) receptor in a tissue preparation of rat small
      intestine was investigated by using [3H]granisetron as a radioligand. Scatchard
      analysis of specific [3H]granisetron binding revealed a single population of
      saturable binding sites in the tissue preparation. At this site, azasetron was
      concentration-dependently competitive with [3H]granisetron, and it inhibited the
      specific [3H]granisetron binding with a Ki value of 0.33 nM. Azasetron has a high
      affinity for 5-HT3 receptor in the gastrointestinal organ, the very site of its
      antiemetic action against chemotherapy-induced emesis.

PMID- 9165375
TI  - Effects of ovariectomy and estrogen replacement on aorta angiotensin-converting
      enzyme activity in rats.
AB  - We investigated the possibility that physiological doses of estrogen protect
      against atherosclerotic change produced by changes in vascular angiotensin
      converting enzyme (ACE) activity. Rats were ovariectomized, and after 14 days,
      treated with estradiol-17 beta (0.2 microgram/rat) for 14 weeks. Aorta ACE
      activity significantly increased in the ovariectomized rats, and decreased
      following estradiol-17 beta administration to a level not different from
      proestrous control rats. These results suggest that the lack of estrogenic action
      increases atherosclerotic change associated with changes in aorta ACE activity
      and that estrogen replacement therapy reduces the risk of atherosclerotic change
      associated with the decrease of aorta ACE activity.

PMID- 9165376
TI  - Cardioprotective effect of K-7259, a novel dilazep derivative, against ischemia
      reperfusion damage in isolated, working rat hearts.
AB  - Global ischemia (15 min) followed by reperfusion (10, 20 or 30 min) was performed
      in isolated, working rat hearts. Ischemia depressed mechanical function, which
      was not restored by reperfusion of 20 min. Preischemic administration of K-7259
      (N,N'-bis[4-(3,4,5-trimethoxyphenyl)butyl]homopiperazine dihydrochloride) (1, 5
      or 10 microM) decreased the function before ischemia, but it attenuated the
      ischemia-induced dysfunction during reperfusion (20 min). Postischemic
      administration of K-7259 (10 microM) or dilazep (20 microM) also attenuated the
      ischemia-induced dysfunction during reperfusion (30 min). Ischemia-reperfusion
      (10 min) increased the tissue malondialdehyde level, and postischemic
      administration of K-7259 (10 microM) or dilazep (20 microM) attenuated the
      malondialdehyde accumulation. K-7259 has a cardioprotective effect when given
      either before or after ischemia.

PMID- 9165377
TI  - Ether extract of fetal calf serum protects cultured rat cortical neurons against
      glutamate cytotoxicity.
AB  - The effects of an ether extract of fetal calf serum (EE-FCS) on glutamate-induced
      cytotoxicity were examined using primary cultures of rat cortical neurons. The
      simultaneous addition of EE-FCS and glutamate reduced glutamate cytotoxicity in a
      concentration-dependent manner. EE-FCS also reduced the cytotoxicity induced by S
      nitrosocysteine, a nitric oxide (NO) donor. The findings indicate that EE-FCS
      contains lipid-soluble, non-peptide substances with neuroprotective actions
      against NO-mediated glutamate neurotoxicity.

PMID- 9165378
TI  - Differential G protein measures in mononuclear leukocytes of patients with
      bipolar mood disorder are state dependent.
AB  - Quantitative and functional measurements of G proteins were undertaken in
      mononuclear leukocytes of bipolar disordered patients comparing bipolar depressed
      with manic patients groups in order to verify whether any alterations observed in
      G protein functional or immunoreactive measures in bipolar mood disorder are
      state- or trait-dependent characteristics. Compared with the control group of 30
      subjects, isoproterenol- and carbamylcholine-enhanced Gpp(NH)p binding capacities
      were highly significantly increased in the group of 20 manic patients, while
      highly significantly reduced in the group of 11 bipolar depressed patients. While
      manic patients showed highly significant elevations in mononuclear leukocytes
      levels of G alpha s and G alpha i, evaluated through immunoblot analysis using
      specific polyclonal antibodies against the subunit proteins, mononuclear
      leukocytes of bipolar depressed patients show significant reductions in G alpha s
      and G alpha i immunoreactive levels. G beta subunit levels were found to be
      similar in all three groups. The changes in G protein measures observed in
      mononuclear leukocytes of mood disordered patients thus represent state
      characteristics of the disorder.

PMID- 9165379
TI  - Amisulpride versus imipramine and placebo in dysthymia and major depression.
      Amisulpride Study Group.
AB  - Amisulpride, a selective antagonist of D2 and D3 dopamine receptors, acts
      preferentially on presynaptic receptors increasing dopaminergic transmission at
      low doses. In a multicentre, 6 months, placebo-controlled trial, amisulpride (50
      mg/daily) was compared to imipramine (100 mg/daily) in the treatment of patients
      with DSM-III-R criteria for primary dysthymia, dysthymia with major depression or
      major depression in partial remission. A total of 219 patients were included.
      Both analyses (intention-to-treat and "per protocol' analysis) detected
      significant differences between groups (active treatment vs. placebo) on all main
      rating scales (CGI, MADRS, ERD, and SANS). The number of patients reporting at
      least one adverse event was higher in the imipramine group than in the two other,
      mainly due to anticholinergic effects. Endocrine symptoms were more frequent in
      female patients treated with amisulpride. These results confirm the interest of a
      drug acting on dopaminergic transmission such as amisulpride in the treatment of
      depressed patients.

PMID- 9165380
TI  - The functioning and well-being of patients with unrecognized anxiety disorders
      and major depressive disorder.
AB  - This study examines the degree to which untreated anxiety disorders and major
      depressive disorder, occurring either singly or in combination, reduce
      functioning and well-being among primary care patients. Adult patients were
      screened using the SCL-52 to identify those with clinically significant anxiety
      symptoms. They also completed the Rand Short-Form (SF-36) to measure self
      reported patient functioning and well-being. Patients with untreated disorders
      were identified using the Q-DIS-III-R to diagnose six DIS-anxiety disorders
      (generalized anxiety disorder, post-traumatic stress disorder (PTSD), simple
      phobia, social phobia, panic/agoraphobia, obsessive/compulsive disorder) and
      major depression. Of 319 patients identified, 137 (43%) had a single disorder and
      182 (57%) had multiple disorders. Regression models estimated the relative
      effects of these disorders on health status (SF-36) by comparing patients with
      the disorders to patients screened as being not-anxious. Estimates of these
      effects were consistent with available national norms. The estimated effect of
      each single disorder on all subscales for physical, social and emotional
      functioning was negative, often as much as a 20-30 point reduction on this 100
      point scale. Major depression had the greatest negative impact, followed by PTSD
      and panic/ agoraphobia. For patients with multiple disorders, the presence of
      major depression was associated with the greatest reduction in functioning
      status. The impact of untreated anxiety disorders and major depressive disorder
      on functioning was comparable to, or greater than, the effects of medical
      conditions such as low back pain, arthritis, diabetes and heart disease.

PMID- 9165381
TI  - Accurate heartbeat perception in panic disorder: fact and artefact.
AB  - The hypothesis was investigated that more accurate perception of heartbeats by
      patients with panic disorder is an artefact of arousal. Twenty-three patients
      with panic disorder, 16 patients with a mood disorder and 21 normal controls were
      tested. There were more panic patients who accurately perceived their heart rates
      (N = 7) than depressed patients (N = 0) or normals (N = 2). The nine accurate
      perceivers had higher scores on questionnaires measuring the cognitions
      associated with panic. For non-accurate perceivers, perceived heart rates were
      unrelated to actual heart rates, unrelated to cognitive factors, but
      significantly related to arousal. It is concluded that the accurate perception of
      heartbeats by patients with panic disorder is both fact and artefact: some
      patients are accurate perceivers, but the majority are not.

PMID- 9165382
TI  - A prospective test of criteria for response, remission, relapse, recovery, and
      recurrence in depressed patients treated with cognitive behavior therapy.
AB  - The definitions that are commonly employed to describe the outcome of the
      depressive disorders are often used in inconsistent ways and remain largely
      untested. The lack of a standard and valid set of outcome definitions hinders the
      study of the naturalistic course and treatment of depressive disorders. In the
      present study, we operationalized definitions for response, remission, relapse,
      recovery, and recurrence and examined their validity in a sample of depressed
      patients treated with cognitive behavior therapy. Validity was evaluated by the
      ability of the definitions to predict subsequent outcome in acute treatment and
      during a 3 year follow-up period. All five definitions demonstrated moderate to
      excellent validity. Moreover, we were able to empirically distinguish response
      from remission, and relapse from recurrence, despite the frequent confusion of
      these terms in the literature. Several of the findings suggest that continued
      refinement of the outcome definitions may enhance validity even further.

PMID- 9165383
TI  - Hypothalamic-pituitary-thyroid-axis function in treatment resistant depression.
AB  - Recently, there were some reports that the prevalence of various grades of
      hypothyroidism may be increased in patients with treatment resistant depression
      (TRD). The aim of the present study was to examine serum basal thyroid
      stimulating hormone (TSH) and thyroxine (T4) levels in 36 major depressed
      subjects, of whom 27 had TRD and 15 were normal volunteers. There were no
      significant differences in serum basal TSH or T4 levels between major depressed
      subjects and normal controls, or between patients with TRD versus normal controls
      or subjects without TRD. There was a trend towards lower serum basal T4
      concentrations in patients with TRD than in other depressed patients and normal
      controls. One patient with TRD had basal serum TSH levels in the hyperthyroid
      range. Two subjects, one with TRD and one normal control, had serum TSH values in
      the subclinical hypothyroid zone, but their serum T4 values were in the euthyroid
      range. There were no significant relationships between basal TSH or T4 and
      severity of illness, staging of depression based on prior treatment non-response,
      length of the depressive episode, duration of illness, or number of previous
      depressive episodes. In conclusion, the results of this study do not provide
      evidence that (subclinical) hypothyroidism occurs more than coincidentally in
      depressed patients with TRD.

PMID- 9165384
TI  - Lithium versus carbamazepine in the maintenance treatment of bipolar disorders--a
      randomised study.
AB  - In a randomised multicentre study, the prophylactic efficacy of lithium and
      carbamazepine was compared in 144 patients with bipolar disorder (74 vs. 70
      patients; observation period: 2.5 years; lithium serum level: 0.63 +/- 0.12
      mmol/l, carbamazepine dose: 621 +/- 186 mg/day). Hospitalisations, recurrences,
      need of psychotropic comedication and adverse effects prompting discontinuation
      were defined as treatment failures. Survival analyses regarding hospitalisations
      and recurrences showed no statistically significant differences between both
      drugs. Results were distinctly in favour of lithium, considering recurrences
      combined with comedication (P = 0.041) and/or adverse effects (P = 0.007).
      Whereas adverse effects prompting discontinuation were more frequent under
      carbamazepine (9 vs. 4, ns), lithium patients reported more often slight/moderate
      side effects (61% vs. 21% after 2.5 years; P = 0.0006). In completers,
      recurrences occurred in 28% (lithium) vs. 47% (carbamazepine) of the patients (P
      = 0.06). Lithium seems to be superior to carbamazepine in maintenance treatment
      of bipolar disorder, in particular when applying broader outcome criteria
      including psychotropic comedication and severe side effects.

PMID- 9165385
TI  - Prevalence of bipolar II disorder in outpatient depression: a 203-case study in
      private practice.
AB  - Of 203 consecutive major depressed outpatients in a private setting, 45% had
      bipolar II disorder, 51% had unipolar depression, and 4% had bipolar I disorder.
      The observed prevalence of bipolar II disorder was higher then previously
      reported in clinical samples (10-40%). Bipolar II disorder had age at baseline
      and onset lower than unipolar depression, and more atypical features. Other
      variables (baseline depression severity, number of depressive episodes,
      psychosis, chronicity, comorbidity) were similar, suggesting that the depressive
      phase of bipolar II disorder differs only in one, but important, dimension
      (atypical features) from unipolar depression in a private setting.

PMID- 9165386
TI  - ESB Research Award 1996. Biophysical stimuli on cells during tissue
      differentiation at implant interfaces.
AB  - If musculoskeletal tissues are indeed efficient for their mechanical function, it
      is most reasonable to assume that this is achieved because the mechanical
      environment in the tissue influences cell differentiation and expression.
      Although mechanical stimuli can influence the transport of bioactive factors,
      cell deformation and cytoskeletal strain, the question of whether or not they
      have the potential to regulate tissue differentiation sequences (for example,
      during fracture healing or embryogenesis) has not been answered. To assess the
      feasibility of biophysical stimuli as mediators of tissue differentiation, we
      analysed interfacial tissue formation adjacent to a micromotion device implanted
      into the condyles of dogs. A biphasic finite element model was used and the
      mechanical environment in the tissue was characterised in terms of (i) forces
      opposing implant motion, (ii) relative velocity between constituents, (iii) fluid
      pressure, (iv) deformation of the tissue and (v) strain in the tissue. It was
      predicted that, as tissue differentiation progressed, subtle but systematic
      mechanical changes occur on cells in the interfacial tissue. Specifically, as the
      forces opposing motion increase, the implant changes from being controlled by the
      maximum-allowable displacement (motion-control) to being controlled by the
      maximum-available load (force-control). This causes a decrease in the velocity of
      the fluid phase relative to the solid phase and a drop in interstitial fluid
      pressure accompanied by a reduction in peri-prosthetic tissue strains. The
      variation of biophysical stimuli within the tissue can be plotted as 'mechano
      regulatory pathway', which identifies the transition from motion-control to force
      control as a branching event in the tissue differentiation sequence.

PMID- 9165387
TI  - The mechanical properties of simulated collagen fibrils.
AB  - Previous theoretical studies of the mechanical properties of tissues such as
      skin, bone and tendon, have used approaches based on composite materials and have
      tended to neglect the contribution of individual microscopic components. In this
      paper, we examine the relationship between the fine structure of a collagen
      fibril and its relative tensile strength. Collagen is a fibrous protein which
      provides associated tissues with the majority of their tensile strength. It is
      present in the form of elongated structures termed fibrils which are created by
      the self-assembly of rod-like collagen molecules in an entropy-driven process
      termed fibrillogenesis. Mutations that alter the primary structure of the
      collagen molecule, interfere with this assembly process and can lead to the
      potentially fatal brittle bone disease, osteogenesis imperfecta. Here we
      investigate the mechanical properties of a range of computer-generated
      aggregates. The aggregates, created by the diffusion limited aggregation of rods,
      were subjected to a simple tensile test based on local rules of damage
      accumulation. In the test, core samples are "extracted' from the aggregates, and
      the network of particles involved in the transmission of stress resolved.
      Increasing stress applied to the core leads to the removal of individual rods
      from this network; the tensile strength is determined from the force necessary to
      form a discontinuous network. Using this approach, we have shown that collagen
      fibril morphology is critical in determining its tensile strength. We suggest a
      possible mechanism to account for the increasing severity of osteogenesis
      imperfecta associated with the distance of mutation from the N-terminal of the
      collagen molecule.

PMID- 9165388
TI  - A uniform strain criterion for trabecular bone adaptation: do continuum-level
      strain gradients drive adaptation?
AB  - In this paper, it is postulated that the apparent density of trabecular bone
      adapts so that continuum-level strains within the bone are uniform and, as a
      consequence, spatial strain gradients within the bone/marrow continuum are
      minimized. The feasibility of a uniform strain criterion was tested using
      computational finite-element analysis of the proximal femur. We demonstrated that
      (1) this criterion produced a realistic apparent density distribution in the
      proximal femur, (2) the solutions for apparent density were convergent and
      unique, (3) predicted apparent densities compared well to experimental
      measurements, and (4) strain gradients within the bone/marrow continuum were
      reduced substantially. Thus, a possible goal of trabecular bone adaptation may be
      the reduction of strain gradients within the bone/marrow continuum. Osteocytes
      within the bone tissue and bone cells on the surface of a trabeculum are
      mechanosensitive and play a role in bone adaptation. In addition, the bone marrow
      is rich in osteoprogenitor cells near the bone surface that are mechanosensitive.
      Strain gradients within bone/marrow continuum cause pressure gradients in the
      marrow, causing extracellular fluid flow which could stimulate osteoprogenitor
      cells and contribute to bone adaptation.

PMID- 9165389
TI  - Convective mass transfer at the carotid bifurcation.
AB  - The convective conditions in regions of hemodynamic separation may produce uneven
      local mass transfer at the arterial wall which may lead to an atherogenic
      response. This study estimates the potential variation in local mass transfer of
      oxygen at the human carotid bifurcation under steady flow conditions. The three
      dimensional separated flow at the bifurcation was studied using a computational
      analysis of the basic conservation equations of mass, momentum, and species. Mass
      transfer between the blood and the wall was estimated throughout the sinus region
      for a condition where the concentration at the wall was constant. Flow separation
      at the carotid bifurcation created a complex concentration field. The mass
      transfer was five times lower along the outer wall of the carotid sinus than the
      artery wall immediately upstream or downstream of the sinus. The region of low
      mass transfer was similar to the region of low shear stress but not identical.
      This distribution of low mass transfer correlated strongly with intimal
      thickening as measured previously from human specimens. Quantitative differences
      in mass transfer at the arterial wall should not be discarded as an important
      mechanism by which hemodynamics influences atherogenesis at this site of clinical
      disease.

PMID- 9165390
TI  - Tensile property of atheromatous plaque and an analysis of stress in
      atherosclerotic wall.
AB  - To know the contributions of blood pressure induced stress to the progression of
      atherosclerosis and the rupture of atheroma, cross-sectional distributions of
      stresses in atherosclerotic walls were calculated by finite element method, using
      stress-strain data of aortic walls and atherosclerotic plaques obtained from
      hypercholesterolemic rabbits. In the aortic wall attached by a local plaque,
      circumferential tensile stress was maximal in the wall near plaque edge, and the
      stress value was very high compared to the tensile strength of wall media. This
      local stress concentration may be a contributing factor to the progression of
      atherosclerotic disease. In the aortic wall uniformly lined with atheroma,
      circumferential stress was high in the innermost layer of atheroma, and its
      magnitude was comparable to the tensile strength of plaque. Stress gradient at
      the interface between atheroma and wall was also high. These results indicate a
      possibility of rupture of atheroma near the intraluminal surface of atheroma or
      at the junction of atheroma with wall intima.

PMID- 9165391
TI  - Intralimb dynamics simplify reactive control strategies during locomotion.
AB  - The utilization of passive dynamics to control the swing trajectory is one
      mechanism which serves to minimize energy costs during locomotion, in addition to
      reducing the complexity of the neural control. In a reactive situation (e.g. trip
      or slip during walking), the energy cost may not be a major determinant of the
      locomotor activity as there is a need for quick corrective action under the
      threat of a fall. Therefore, we addressed the following question: does the
      nervous system utilize passive dynamics during the reactive control of
      locomotion? An unexpected mechanical perturbation was applied to the foot during
      early and late swing during walking. Video data were input into an inverse
      dynamics routine to obtain the joint moment and mechanical power profiles and to
      partition the joint moments into active and passive components. The nervous
      system still utilized the passive dynamics of the effector system; active control
      of a single joint, the knee joint, passively facilitated the flexor action at the
      proximal hip and distal ankle joint following the early swing perturbation. The
      minimization of the mechanical energy cost was not a major determinant for this
      task since the total mechanical work during the perturbed steps was greater than
      during normal steps. A neuromuscular constraint was observed following the late
      swing perturbation; the active control of the hip and knee joints were increased
      but the magnitude of the hip extensor/knee flexor moment was invariant and equal
      to 1.6. The intralimb dynamics identified during these responses may serve to
      simplify the complexity of the active control of the nervous system.

PMID- 9165392
TI  - Compressive behavior of articular cartilage is not completely explained by
      proteoglycan osmotic pressure.
AB  - It has been hypothesized that applied mechanical or osmotic loads which decrease
      cartilage volume by 5% or more are sufficient to relieve all collagen tensile
      forces, and that further changes in the applied load are completely supported by
      changes in proteoglycan osmotic pressure. In this view, cartilage should behave
      mechanically like a concentrated solution of proteoglycans. We tested this
      hypothesis by measuring the equilibrium axial and radial stresses in bovine
      articular cartilage during uniaxial confined compression. If the hypothesis is
      correct, the observed changes in the radial and axial stresses in confined
      compression should be equal for compression greater than 5%. However, the
      observed change in axial stress was always substantially greater than the change
      in radial stress over the range of strains (5-26%) and saline concentrations
      (0.05-0.15 M) tested. This indicates that the mechanical behavior of cartilage in
      confined compression cannot solely be explained by changes in proteoglycan
      osmotic pressure even for strains as large as 26%. A linear isotropic model was
      found to describe the observed equilibrium behavior adequately. In addition, the
      inferred shear modulus was found to be independent of saline concentration and
      similar to measurements by others of the flow-independent shear modulus. Our
      results have implications regarding the relative contribution of the
      proteoglycans and collagen to the mechanical properties of the tissue in
      compression, and suggest that tensile forces in the collagen network may play an
      important role in determining tissue behavior in confined compression even for
      relatively large volume changes.

PMID- 9165393
TI  - Muscle coordination of maximum-speed pedaling.
AB  - A simulation based on a forward dynamical musculoskeletal model was computed from
      an optimal control algorithm to understand uni- and bi-articular muscle
      coordination of maximum-speed startup pedaling. The muscle excitations, pedal
      reaction forces, and crank and pedal kinematics of the simulation agreed with
      measurements from subjects. Over the crank cycle, uniarticular hip and knee
      extensor muscles provide 55% of the propulsive energy, even though 27% of the
      amount they produce in the downstroke is absorbed in the upstroke. Only 44% of
      the energy produced by these muscles during downstroke is delivered to the crank
      directly. The other 56% is delivered to the limb segments, and then transferred
      to the crank by the ankle plantarflexors. The plantarflexors, especially soleus,
      also prevent knee hyperextension, by slowing the knee extension being produced
      during downstroke by the other muscles, including hamstrings. Hamstrings and
      rectus femoris make smooth pedaling possible by propelling the crank through the
      stroke transitions. Other simulations showed that pedaling can be performed well
      by partitioning all the muscles in a leg into two pairs of phase-controlled
      alternating functional groups, with each group also alternating with its
      contralateral counterpart. In this scheme, the uniarticular hip/knee extensor
      muscles (one group) are excited during downstroke, and the uniarticular hip/knee
      flexor muscles (the alternating group) during upstroke. The ankle dorsiflexor and
      rectus femoris muscles (one group of the other pair) are excited near the
      transition from upstroke to downstroke, and the ankle plantarflexors and
      hamstrings muscles (the alternating group) during the downstroke to upstroke
      transition. We conclude that these alternating functional muscle groups might
      represent a centrally generated primitive for not only pedaling but also other
      locomotor tasks as well.

PMID- 9165394
TI  - Adaptive bone remodeling incorporating simultaneous density and anisotropy
      considerations.
AB  - Over 100 years ago, Wolff hypothesized that cancellous bone altered both its
      apparent density and trabecular orientation in response to mechanical loads. A
      mathematical counterpart of this principle is derived by adding a remodeling rule
      for the rate-of-change of the full anisotropic stiffness tensor (all 21
      independent terms) to the density rate-of-change rule adapted from an existing
      isotropic theory. As a result, anisotropy and density patterns develop such that
      the local stiffness tensor is optimal for the given series of applied loadings.
      The method does not rely on additional morphological measures of trabecular
      orientation. Furthermore, assumptions of material symmetry are not required, and
      any observed regions of orthotropy, transverse isotropy, or isotropy are a result
      entirely of the functional adaptation of the bone and not the consequence of a
      modeling assumption. This approach has been implemented with the finite element
      method and applied to a two-dimensional model of the proximal femur with
      encouraging results.

PMID- 9165395
TI  - The effect of insoles in therapeutic footwear--a finite element approach.
AB  - Current practice in the prevention of recurrence of neuropathic foot ulcers is to
      prescribe accommodative in-shoe orthoses or insoles which reduce plantar pressure
      levels at locations of bony prominences, particularly under the metatarsal heads.
      To date, design of these orthoses has largely been a trial and error process.
      There is little quantitative information available regarding the effects of
      thickness and the influence of soft tissue characteristics on the cushioning
      effect of such interventions. The current paper investigated alterations in
      pressure under the second metatarsal head as a function of insole thickness and
      tissue thickness. Both experimental and quasi-static plane strain finite element
      approaches were employed. The orthoses chosen reduced plantar pressure by a
      maximum of approximately 30% and were more effective (on a percentage basis) in
      the setting of reduced sub-metatarsal tissue thickness. Peak normal stresses
      predicted by the FE models were, on average, within 5.9% of experimentally
      measured values for the normal tissue case and 8.1% for the reduced tissue case.
      The techniques presented represent a promising approach to understanding plantar
      cushioning and the principles involved in the design of therapeutic footwear for
      insensate feet.

PMID- 9165396
TI  - Relationship between bone-prosthesis bonding and load transfer in total hip
      reconstruction.
AB  - The effect of bone-prosthesis bonding on proximal load transfer is investigated
      using a coupled experimental and finite element analysis on a synthetic femur.
      Three-dimensional finite element models for an intact femur and a femur implanted
      with a cementless prosthesis were constructed from the experimental models used,
      and the proximal femoral strains recorded for two loading conditions
      approximating a one-legged stance. The approach was used to investigate a press
      fitted and a fully bonded bone-prosthesis structure to identify the stem-bone
      behaviour for both interface conditions and their implications for proximal bone
      load transfer. Regression slopes close to unity indicated that the finite element
      predictions were an accurate estimate of the experimental measurements.
      Physiological surface strains were recorded only when the abductor force was
      included in the loading. Meanwhile, experimental measurements and numerical
      predictions showed that a different load transfer pattern is to be expected for
      normally press-fitted and glued press-fitted stems. The finite element model for
      the treated femur, modelling both interface conditions correlated very well with
      the experimental model. These finite element models subsequently modified and
      used to analyse the effect of different interface conditions predicted a
      significant increase in the load transfer to the proximal calcar bone when only
      proximal bonding is achieved. This study suggests that information obtained for
      the assessment and prediction of total hip arthroplasty longevity by numerical
      and experimental techniques used together and in parallel is of greater value
      than either technique used alone. The employment of a femur analogue as featured
      in this study is also shown to be a suitable alternative to cadaveric specimens
      in such an analysis.

PMID- 9165397
TI  - Forces and moments generated at the dental incisors during forceful biting in
      humans.
AB  - A miniature load sensor capable of measuring all forces and all moments
      simultaneously at a single location in space was used to assess the magnitude and
      direction of loads that affect the dental incisors during forceful, static
      biting. While prior approaches have not measured all necessary six degrees of
      freedom during biting, the complete set of loads is needed to serve as realistic
      boundary conditions for analytical or computational models of mandibular
      mechanics. Four subjects were asked to perform controlled and repetitive edge-to
      edge incisal biting activities. Customized devices were used to rigidly hold the
      load sensor in place at pre-specified tooth separations of less than 1 mm. The
      results yielded force resultants with a magnitude range of 24.5 to 28.4 N. This
      range was intentionally limited in magnitude to avoid damage to the internal
      strain gauge assembly of the sensor. In all cases, the highest force component
      was oriented upwards. An additional simultaneous moment resultant (range: 8.9
      17.0 N cm) with a main moment component oriented backwards and downwards towards
      the oral cavity was also detected. These data suggest that in order for the
      biting loads to be composed of six DOF, the remaining forces acting on the
      mandibular force system (i.e. muscular and/or articular) may indeed be non
      coplanar and non-concurrent. Although useful for static biting activities, the
      bulk of the sensor would probably preclude meaningful measurements during dynamic
      events such as chewing or swallowing.

PMID- 9165398
TI  - A comparison of different methods in predicting static pressure distribution in
      articulating joints.
AB  - Pressure distribution along the contact surface of an articulating joint model
      was analyzed using different numerical and analytical methods: a discrete rigid
      element method [rigid-body-spring-model (RBSM)], the finite element method (FEM),
      a simplified elasticity solution (SES) and the modified Hertzian (MH) theory. The
      FEM and MH methods modeled joints interposed with elastic layers, while the RBSM
      and SES methods assumed a simplified joint with a rigid convex indenter on an
      elastic concave surface. Results for an axisymmetric joint model indicate that
      all of these methods predict similar pressure distributions on joint surfaces. In
      non-axisymmetric deformation mode, the RBSM method and FEM calculation showed
      good agreement in contact pressure prediction. Compared to the other three
      methods, the RBSM is relatively simple and effective in predicting joint contact
      pressure under symmetric and non-symmetric loading. The computational efficiency
      of the RBSM method is particularly attractive for pre-operative planning of
      reconstructive surgical procedures in orthopaedics in which geometric changes
      dictate the eventual outcome of the surgery.

PMID- 9165399
TI  - The role of backside polishing, cup angle, and polyethylene thickness on the
      contact stresses in metal-backed acetabular components.
AB  - Mechanical interactions between the polyethylene liner and the metal-backing play
      an important role in the load transfer and debris-generation mechanisms of an
      acetabular component. Insert thickness, cup orientation, and insert-shell
      interface conditions affect the resulting contact stresses at the articulating
      and backside surfaces of the polyethylene component. The objective of this study
      was to determine the variation in contact stresses on a hemispherical acetabular
      component as a function of the friction coefficient of the line-shell interface,
      the thickness of the insert, and the load application angle. Three-dimensional
      finite element models of a metal-backed acetabular component with liner
      thicknesses of 3-12 mm were developed. The insert-shell interface was modeled as
      either matte or highly polished, and the load angle of the joint reaction force
      was changed from 36 to 63 degrees with respect to the dome. We found that the
      contact stresses at the articulating and backside surfaces of the insert were
      relatively insensitive to changes in the coefficient of friction at the insert
      shell interface (resulting in approximately 1-10% variation in contact stress),
      when compared to the effect of changing the insert's thickness (approximately 80%
      variation in contact stress) or changing the direction of the joint reaction
      force (approximately 20% variation in contact stress). The results of this study
      suggest that polishing the metal at the insert-shell interface does not
      substantially change the contact stresses at either surface of the component. Of
      the design variables available for selective modification by either the surgeon
      or the engineer, insert thickness and shell orientation play a greater role in
      determining the magnitude of the resulting contact stresses.

PMID- 9165400
TI  - The Cybermouse: a simple method of describing the trajectory of the human
      mandible in three dimensions.
AB  - A simple method of recording the three-dimensional movements of the mandible
      together with up to 10 channels of other physiological data is described. The
      system is based on a commercially available device, the Cybermouse (IPC,
      Freemont, CA, U.S.A.), consisting of a lightweight ultrasonic emitter which can
      be attached to the chin by means of an elasticated band, and a base unit which
      contains three ultrasonic detectors. A microprocessor in the base unit calculates
      the position of the emitter by analysing the differences in the times of arrival
      of signals from the emitter. Physiological data is acquired using the PICO-ADC11
      (Pico Technology, Cambridge, U.K.) a 10-channel analogue-to-digital converter. As
      an example, an application where temporomandibular joint sounds and mandibular
      movement data were collected simultaneously is described. The Cybermouse is of
      sufficient accuracy for use in most situations, and its ease of use and
      relatively low cost outweights its few disadvantages when compared to more
      complex systems.

PMID- 9165401
TI  - Parameters for modeling the upper extremity.
AB  - The purpose of this paper was to provide parameters for the development of a
      musculoskeletal model of the upper extremity. Five upper extremity specimens were
      obtained from four fresh cadavers. Anthropometric measures were obtained for each
      cadaver. Segment inertial parameters were estimated for each specimen from
      anthropometric measures of the cadaver from which the specimen was obtained. The
      three-dimensional kinematics of the humerus, ulna, and radius in different
      movements of the glenohumeral, humeroulnar and ulnoradial joints were measured
      for each specimen using of the 3Space tracking system (Isotrack, Polhemus). The
      instantaneous rotation center of the glenohumeral joint and the instantaneous
      rotation axes of elbow flexion and forearm pronation were determined for each
      specimen from the kinematic data. The specimens were dissected and the muscle
      origins and insertions and bony structures needed in upper extremity modeling
      were digitized using the 3Space system. The shapes of muscle origins and
      insertions were estimated. Muscle length, volume and pennation angle were
      measured for the estimation of physiological cross-sectional areas of each
      muscle. The results, which are given for one specimen, showed that the rotation
      center of the glenohumeral joint was very close to the geometric center of the
      joint with a mean distance of 4 mm. The mean angle between the flexion-extension
      and pro-supination axes of the elbow joint was 94 degrees. The minimum distance
      between these two axes was about 4 mm.

PMID- 9165403
TI  - Secondary epileptogenesis.

PMID- 9165402
TI  - Inertial properties of Dutch Warmblood horses.
AB  - The complete set of three-dimensional inertial properties (mass, density, centre
      of mass, inertial tensor) was determined in 26 segments of six Dutch Warmblood
      horses. The measurements were performed with frozen segments similar to the
      procedure described by Lephart (1984, J. Biomechanics 17, 537-543). Based on
      these data linear regression models were developed for the estimation of inertial
      properties in living horses. The reproducibility of the dissection procedure was
      found to range between 2 and 9%. Both mean values and regression models are
      presented for all parameters. The mean standard error of estimation was 8% for
      the segment mass, 3% of the segment reference length for the position of the
      centre of mass, and 17% for the moments of inertia.

PMID- 9165404
TI  - Hypothetical mechanisms for the cellular and neurophysiologic basis of secondary
      epileptogenesis: proposed role of synaptic reorganization.
AB  - This review article evaluates the hypothetical cellular mechanisms responsible
      for chronic lesion-induced epilepsy. Emphasis is given to particular clinical
      characteristics of secondary epileptogenesis: (a) a temporal latency, (b) the
      involvement of distant but related sites, and (c) irreversibility. Although loss
      of GABAergic inhibitory interneurons or increased excitatory input to these
      interneurons may contribute to epileptogenesis, several studies have provided
      evidence that inhibition is not depressed in epileptogenic regions and may
      actually be enhanced. Axonal sprouting, synaptic reorganization, and formation of
      new recurrent excitatory circuits have been proposed to account for the increased
      seizure susceptibility of temporal lobe epilepsy. Recent data support the
      hypothesis that local inhibitory circuits mask the multisynaptic excitatory
      interactions that are associated with mossy fiber sprouting in the dentate gyrus
      and that physiological mechanisms that reduce inhibition or increase excitability
      unmask the new recurrent excitatory circuits responsible for seizures. A
      hypothesis based on axonal sprouting and synaptic reorganization can account for
      the essential clinical characteristics of secondary epileptogenesis and may have
      widespread applicability to the general phenomenon of lesion-induced epilepsy.

PMID- 9165405
TI  - Do seizures beget seizures? An assessment of the clinical evidence in humans.
AB  - For more than a century, epilepsy was characterized as a chronic disease, with
      little chance of remission or cure. It was also considered a progressive disease
      in which seizures led to more seizures. Experimental work in animals provided
      additional support for the notion that seizures could beget seizures. However,
      the earliest clinical observations in humans were based on highly selected,
      largely refractory patients. Furthermore, the experimental work in animals bore
      little relation to naturally occurring seizures and epilepsy in humans. Evidence
      from multiple sources regarding the nature and natural history of seizures and
      epilepsy in humans has repeatedly demonstrated that in most cases of occurrence
      of seizures itself does not influence the long-term outcome of epilepsy.
      Consequently, interventions to prevent seizures early in the course of a seizures
      disorder do not alter the natural history of seizure disorders with respect to
      whether remission will occur in the long term. That outcome is largely
      predetermined by other factors, many of which are not currently amenable to
      intervention. In some rare syndromes, deterioration is progressive. In these
      instances, it is the underlying syndrome, not the seizures, that is primarily
      responsible for the deterioration. In addition, extremely prolonged seizures
      (which are rare) may also directly cause damage. These are exceptions rather
      than, as previously believed, the rule. The available human data strongly suggest
      that seizures do not beget seizures and that epilepsy in humans is usually not a
      progressive disorder.

PMID- 9165406
TI  - Secondary epileptogenesis in humans.
AB  - Secondary epileptogenesis as it applies to humans remains a controversial topic
      despite 40 years of investigation. Part of the controversy stems from
      disagreement about the definition of secondary epileptogenesis, and part of the
      controversy stems from the imperfect fit of animal models to the human epileptic
      syndromes. It may be that models of secondary epileptogenesis can be useful to
      describe specific epileptic syndromes such as bitemporal epilepsy and secondary
      bilateral synchrony, but other models may be required for remitting syndromes
      such as the Landau-Kleffner syndrome. The concept of secondary epileptogenesis
      may also provide a useful construct for evaluating patients with partial
      epileptic syndromes, especially those under consideration for epilepsy surgery,
      and for the evaluation of preventive strategies in epilepsy.

PMID- 9165407
TI  - In memoriam Frank Morrell: a man ahead of his time. June 4, 1926-October 22,
      1996.

PMID- 9165408
TI  - Computer-aided determination of the silent period.
AB  - Silence of electromyographic (EMG) activity after an evoked muscle twitch has
      been studied extensively. However, different criteria have been used to determine
      the level at which the silence of muscle activity ends, and the purpose of this
      work was to develop an objective method able to determine the silent period even
      when data were acquired using different EMG instruments. The silent period evoked
      by transcranial magnetic stimulation was determined bilaterally from abductor
      pollicis brevis (APB) muscles in 11 subjects, from trapezius muscles in 9
      subjects, and from sternocleidomastoid muscles in 11 subjects. All subjects were
      healthy controls and gave their informed consent to participate in the study.
      Muscle activity was recorded via surface electrodes. Recordings from 10 stimuli
      were rectified, averaged, and plotted logarithmically by dividing the mean of the
      prestimulus EMG activity into the whole trace. Plotted in this way, the one-level
      represents the mean rectified EMG amplitude of the prestimulus activity. The end
      of the silent period was measured automatically as the moment at which Student's
      t test was no longer significantly different, when testing the window of mean
      prestimulus EMG activity with respect to a 4-ms window centered around the
      assumed end of the silent period (resolution 0.1 ms). The mean silent periods
      were 183.7 +/- 49.8 ms for APB, 194.2 +/- 28.8 ms for trapezius, and 194.8 +/-
      73.6 ms for sternocleidomastoid muscles, measured from the M-response latency
      (mean latency: APB 19.7 +/- 1.9 ms, trapezius 7.8 +/- 0.6 ms, and
      sternocleidomastoid 6.7 +/- 0.8 ms). Computer-aided measurement proved to be a
      fast and objective tool able to standardize determination of the silent period.

PMID- 9165409
TI  - The effects of tobacco smoking on the short, middle, and long latency responses
      of the blink reflex in humans.
AB  - The three responses (R1, R2, and R3) of the electrically elicited blink reflex
      (BR) obtained in four normal human subjects were investigated before and after
      smoking both a filtered and an unfiltered cigarette. The changes observed in the
      BR were stronger and statistically more significant for the unfiltered than for
      the filtered cigarette, (p < 0.0001) and were more dramatic in R3 than R1 or R2.
      The action of nicotine on central pathways located at the interneuronal network
      of the brainstem, basal ganglia, and C fiber structures involved with this reflex
      seems to be the most likely mechanism for these findings.

PMID- 9165410
TI  - Clinical accompaniments of the burst-suppression EEG pattern.
AB  - A burst-suppression pattern on the EEG following anoxic insult is usually
      associated with a poor prognosis. Myoclonic jerks may accompany the
      electrographic burst. On rare occasions oral, ocular, or appendicular movements
      can be associated with bursts of EEG activity recorded following cerebral anoxic
      insult. At times these movements may cause confusion about the patient's state of
      consciousness or the purposefulness of the movements; they may mimic volitional
      movements in response to external stimuli. To better describe the variety of
      movements that may accompany bursts of EEG activity in comatose patients, we
      review 12 cases where movements occurred in association with the electrographic
      bursts.

PMID- 9165411
TI  - The way to a man's heart is through his stomach.

PMID- 9165412
TI  - Gastric intramucosal pH changes after volume replacement with hydroxyethyl starch
      or crystalloid in patients undergoing elective abdominal aortic aneurysm repair.
AB  - PURPOSE: Gastric intramucosal pH (pHi), a surrogate marker of tissue oxygenation,
      falls following abdominal aorta aneurysm (AAA) repair. We tested the hypothesis
      that volume replacement with a hydroxyethyl starch solution would result in
      better preserved splanchnic oxygenation than would volume replacement with
      crystalloid solutions. MATERIALS AND METHODS: This was a prospective, randomized,
      nonblinded study set in a university-affiliated community hospital. Thirty
      patients undergoing elective AAA repair were studied. Patients were randomly
      selected to receive intraoperative and postoperative fluid replacement with
      either hetastarch or crystalloid. According to the study protocol, patients could
      not receive in excess of 3,000 mL of hetastarch. Tissue oxygenation was assessed
      indirectly by measuring pHi using a nasogastric tonometer. Hemodynamic,
      oxygenation, and pHi data were collected preoperatively, preclamp, before
      unclamping, at the end of the procedure and postoperatively for 24 hours.
      Coagulation parameters were determined preoperatively and postoperatively for 24
      hours. RESULTS: Fifteen patients were randomized to each group. There were 18
      male and 12 female patients, whose mean age was 66 +/- 9 years. The
      intraoperative fluid balance was significantly greater in the crystalloid
      compared with the hetastarch group (4,194 +/- 1,500 mL v 2,949 +/- 1,123 mL; P =
      .05, 95% confidence interval [C] 23 to 2,519 mL). There were no significant
      differences in the amount of intraoperative blood loss or postoperative
      transfusion requirements between the two groups. The difference between the
      preoperative pHi and nadir was 0.07 +/- 0.03 in the hetastarch group compared
      with 0.13 +/- 0.04 in the crystalloid group (P = .001, Cl 0.03 to 0.09). By
      multivariate analysis the only variable that influenced the fall in pHi was the
      type of resuscitation fluid (F ratio of 7.63; P = .01). There were no significant
      differences in hemodynamic- and oxygenation-derived variables or coagulation
      parameters between the two groups of patients. The length of mechanical
      ventilation, intensive care unit, and hospital stay was comparable between the
      two groups of patients. CONCLUSION: In patients undergoing major surgery, volume
      resuscitation with hydroxyethyl starch solutions may improve microvascular blood
      flow and tissue oxygenation.

PMID- 9165413
TI  - Positive pressure inspiration differentially affects right and left ventricular
      outputs in postoperative cardiac surgery patients.
AB  - PURPOSE: The purpose of this study was to determine the dynamic changes in right
      ventricular (RV) and left ventricular (LV) output during positive airway pressure
      inspiratory hold maneuvers so as to characterize the interaction of processes in
      creating steady-state cardiac output during positive pressure ventilation.
      MATERIALS AND METHODS: We examined the disparity of RV and LV outputs at 5
      seconds (early) and 20 seconds (late) into a 24-second inspiratory hold maneuver
      in 14 subjects in the intensive care unit immediately following coronary artery
      bypass surgery. RV output was measured by the thermodilution technique, whereas
      LV output was measured by the arterial pulse contour method. RV and LV volumes
      were also measured by thermal and radionuclide ejection fraction techniques,
      respectively. RESULTS: As P(aw) was progressively increased from 0 to 20 cm H2O
      in sequential inspiratory hold maneuvers, both RV and LV outputs changed
      differently both at 5 seconds and 20 seconds into the inspiratory hold maneuvers.
      When expressed as change in cardiac output (L/min) for every cm H2O P(aw)
      increase relative to end-expiratory values, RV output increased at 5 seconds
      (0.05 +/- 0.15 L/min) then decreased at 20 seconds (-0.08 +/- 0.21, P < .05). LV
      output decreased slightly at 5 seconds (-0.14 +/- 0.22) and did not change from
      this minimal depressed level at 20 seconds (P < .05). Changes in RV and LV output
      were paralleled by changes in RV and LV end-diastolic volumes, respectively.
      CONCLUSION: Positive pressure inspiration induces time-dependent changes in
      central hemodynamics, which are dissimilar between RV and LV function. Initially,
      inspiration increases RV output but decreases LV output, such that intrathoracic
      blood volume increases. However, sustained inspiratory pressures induce
      proportionally similar decreases in both RV and LV outputs. Thus, the hemodynamic
      effects of positive pressure ventilation will depend on the degree of lung
      inflation, the inspiratory time, and when measurements are made within the
      ventilatory cycle. These data also suggest that positive pressure ventilation
      with up to 20 cm H2) P(aw) does not significantly impair ventricular performance
      in humans.

PMID- 9165414
TI  - Increased plasma concentrations of brain natriuretic peptide in patients with
      acute lung injury.
AB  - PURPOSE: This study was performed to elucidate the pathophysiological role of
      brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in acute
      lung injury. MATERIALS AND METHODS: We sequentially measured plasma
      concentrations of immunoreactive BNP and ANP in 10 patients (mean age, 63 years
      (with acute lung injury and compared those with hemodynamic parameters and
      pulmonary functions. RESULTS: Plasma concentrations of immunoreactive BNP and ANP
      were markedly elevated at entry into the study. Plasma BNP concentrations during
      the early course (3 days) showed significant (P < .01) positive correlations with
      systemic vascular resistance index (r = .708) and pulmonary vascular resistance
      index (r = .573), but a negative correlation with cardiac index (r = .608).
      Plasma ANP concentrations showed a significant (P < .05) positive correlation
      with pulmonary capillary wedge pressure (r = .398). Plasma BNP in 4 patients who
      died and 1 patient with acute renal failure remained elevated during the entire
      hospital length of stay (12 days). CONCLUSION: These findings suggest that
      circulating BNP plays an important role in acute lung injury along with ANP as a
      compensatory mechanism for cardiac dysfunction accompanied by increased systemic
      vascular resistance index and pulmonary vascular resistance index. Circulating
      BNP may be a sensitive humoral marker for the degree of ventricular dysfunction
      associated with acute lung injury.

PMID- 9165415
TI  - Changes in the lung after prolonged positive pressure ventilation in normal
      baboons.
AB  - PURPOSE: The effects of prolonged positive pressure ventilation on lung
      ultrastructure are not well defined in primates. This study was designed to
      measure cardiopulmonary and morphological responses to 4 days of positive
      pressure ventilation in normal baboons. MATERIALS AND METHODS: Six adult male
      baboons were mechanically ventilated on air for 96 hours with 2.5 cm positive end
      expiratory ventilation and a tidal volume of 12 to 15 mL/kg. Physiological
      measurements were obtained every 12 hours and serial measurements of ventilation
      perfusion (VA/Q) were performed using the multiple inert gas elimination
      technique. Quantitative morphotometry, lung dry-to-wet ratio, and surfactant
      analysis were performed at the end of the experiment. RESULTS: Cardiovascular
      variables, except for a small increase in mean pulmonary artery pressure at 84
      and 96 hours, were not significantly affected by positive pressure ventilation.
      Arterial Po2 decreased, and shunt fraction increased from 0.7% of cardiac output
      to 5.4% (P < .01). Dispersion of perfusion increased threefold (P < .01), and
      dispersion of ventilation doubled (P < .01) indicating increased VA/Q mismatch
      mismatch. Respiratory system compliance decreased by 30% (P < .01). There was no
      lung edema or change in surfactant composition. Lung morphometry showed increases
      in polymorphonuclear cells and type II cell volume. Vacuolated endothelial cells
      and bare basement membrane were observed consistently. CONCLUSION: Four days of
      positive pressure ventilation decreases lung compliance and worsens gas exchange
      by increasing shunt and VA/Q mismatch in healthy baboons. These effects are
      accompanied by only minor ultrastructural changes and mild inflammatory responses
      in the lung.

PMID- 9165416
TI  - Endotoxin-induced ileal Vo2-Do2 alterations do not correlate with the severity of
      ileal injury.
AB  - PURPOSE: Altered Vo2-Do2 relationships are most often noted to occur in the
      setting of sepsis or endotoxin (LPS)-induced systemic organ microvascular injury
      and are generally thought to be causally linked to that injury. However, we have
      recently shown that ileal microvascular injury is not associated with altered
      ileal Vo2-Do2, relationships. Thus, we hypothesized that the severity of LPS
      induced systemic organ microvascular injury would not correlate with the
      development of systemic organ Vo2-Do2 alterations. MATERIALS AND METHODS: To test
      this hypothesis, we used the in situ autoperfused feline ileal preparation to
      simultaneously examine microvascular permeability, reflected as the ileal lymph
      to plasma protein concentration ratio (CL/CP), and ileal Vo2-Do2 relationships 2
      hours after intravenous LPS (0.75-2.0 mg/kg; n = 9) and in matching controls (n =
      5). RESULTS: As expected, all LPS-treated animals were found to have extensive
      ileal histological damage and marked increases in the CL/CP compared with
      controls (0.308 +/- 0.019 v 0.097 +/- 0.009; P < .001). In addition, although the
      critical Do2 (Do2c) was elevated in the LPS-treated animals relative to controls
      (34.2 +/- 5.0 v 16.7 +/- 1.4 mL/min/kg; P < .03), there was no correlation
      between the Do2c and the CL/CP in the LPS-treated animals. Finally, ileal wet to
      dry weight ratios after LPS did not differ from controls. CONCLUSION: Taken
      together, these data suggest that factors other than organ injury, as assessed by
      morphological and permeability alterations, are important in the pathogenesis of
      altered systemic organ Vo2-Do2 relationships after LPS.

PMID- 9165417
TI  - Systemic and regional effects of experimental gradual splanchnic ischemia.
AB  - PURPOSE: We evaluated the effects of gradual intestinal ischemia on systemic and
      regional haemodynamics and oxygen transport. MATERIALS AND METHODS: Superior
      mesenteric artery (SMA) blood flow was decreased by 40%, 70%, and 100% for 60
      minute periods and thereafter released in 12 pigs. Hemodynamic changes were
      monitored continuously, and the intestinal perfusion was evaluated by changes in
      portal vein-arterial lactate gradient, intramucosal pH, tonometric Pco2,
      tonometric-portal vein Pco2 gradient, and regional oxygen extraction. RESULTS:
      Local signs of intestinal hypoperfusion developed during the SMA occlusion.
      Intramucosal pH and portal vein pH decreased from 7.18 +/- 0.04 to 6.81 +/- 0.04
      (P < .01) and from 7.36 +/- 0.01 to 7.25 +/- 0.03 (P < .05), respectively.
      Intramucosal Pco2 and tonometric-portal vein Pco2 gradient increased from 12.4 +/
      1.3 to 21.2 +/- 1.8 kPa (P < .01) and from 6.0 +/ 1.3 to 14.0 +/- 1.9 kPa (P <
      .05), respectively. Portal vein-arterial lactate gradient and splanchnic oxygen
      extraction increased from 0.02 +/- 0.07 to 2.32 +/- 0.47 mmol/L (P < .01) and
      from 0.44 +/- 0.03 to 0.60 +/- 0.03 (P < .05), respectively. Systemic changes
      observed during the SMA occlusion were reduction of cardiac index (161 +/- 12 to
      114 +/- 8 mL/min/kg, P < .01) and pulmonary capillary wedge pressure (4 +/- 1 to
      3 +/- 1 mm Hg) and increase in heart rate (124 +/- 5 to 173 +/- 11 beats/ min, P
      < .01) and mean arterial pressure (79 +/- 3 to 104 +/- 5 mm Hg, P > .01).
      Systemic oxygen extraction increased (P > .05), arterial pH increased (P < .05),
      and arterial lactate decreased (P < .01) during the SMA occlusion. Splanchnic
      ischemia defined as an increase in portal vein-arterial lactate gradient above
      mean +2 SD of the baseline occurred at 93 +/- 15 minutes corresponding 70% SMA
      occlusion. CONCLUSION: We conclude that signs of tissue hypoperfusion started to
      develop at 70% SMA occlusion and that regional tissue hypoperfusion in the
      splanchnic region may develop without any systemic signs of oxygen supply/demand
      mismatch.

PMID- 9165418
TI  - Teleradiology for remote diagnosis: a prospective multi-year evaluation.
AB  - Teleradiology has been used for nearly 3 years at our institution to provide
      urgent radiologic interpretations for two outpatient clinics and an affiliated
      hospital. The purpose of this study was to evaluate the clinical reliability of
      the existing system. Teleradiology images were interpreted using 1600 x 1200
      pixel display stations. The original films from the same cases were subsequently
      interpreted, usually by another radiologist. The initial and final
      interpretations were compared. Discrepancies were rated and adjudicated by
      another senior radiologist. These data were compared to peer review interobserver
      discrepancy rates. Among the 2688 teleradiology examinations evaluated, there
      were major discrepancies in 31 (1.5%). In three instances teleradiology rather
      than film interpretation was considered correct. Abnormalities missed on
      teleradiology were apparent in all but two at adjudication. Among the 628 peer
      review cases, there were 6 (0.96%) major discrepancies. Major teleradiology
      discrepancy rates are statistically similar to film-based peer review discrepancy
      rates. Teleradiology is suitable for providing radiologic services to remote
      medical facilities.

PMID- 9165419
TI  - The impact of a picture archiving and communication system on nuclear medicine
      examination interpretation.
AB  - Radiographic correlation is essential for many of the examinations performed in
      nuclear medicine. The purpose of this study was to evaluate the impact of a
      picture archiving and communications system (PACS) on the function and efficiency
      of a nuclear medicine department at a tertiary care institution. We evaluated 250
      consecutive noncardiac nuclear medicine imaging examinations and asked the
      interpreting physician the following questions: (1) Was PACS used in the
      interpretation of the study? (2) Did the use of PACS expedite examination
      completion or aid in study interpretation? And (3) Did the use of PACS permit a
      definitive diagnosis to be made? PACS was accessed for correlative radiographic
      images in 155 of the 250 (62%) nuclear medicine examinations. Images available on
      PACS for review aided in study interpretation in 74% (115 of 155) of cases. The
      use of PACS was thought to expedite examination completion in 55% (86 of 155) of
      cases. The system was accessed but not operational in only 1% of cases (2 of
      155). PACS provides reliable, rapid access to multimodality correlative
      radiographic images that aid in the interpretation of nuclear medicine
      examinations. Such systems also increase the efficiency of a nuclear medicine
      service by allowing timely and conclusive interpretations to be made.

PMID- 9165420
TI  - A computerized analysis system in chest radiography: evaluation of interstitial
      lung abnormalities.
AB  - We evaluated the usefulness of a computerized analysis system in the detection of
      interstitial lung abnormalities in digitized chest radiography. This system uses
      the processes of four-directional Laplacian-Gaussian filtering, linear opacity
      judgment, and linear opacity subtraction. For qualitative analysis, we employed a
      combined radiographic index, which was calculated from two normalized
      radiographic indices obtained by linear opacity judgment and subtraction of
      linear opacities. We selected 50 regions of interest (ROIs) in patients with mild
      interstitial lung abnormalities, 50 ROIs in patients with severe interstitial
      lung abnormalities, and 50 ROIs in individuals with normal lung parenchyma. High
      resolution computed radiography (HRCT) findings were used as the standard of
      reference for this study. These ROIs were processed by our computerized analysis
      system, and radiographic indices were obtained from each ROI. The area under the
      receiver operating characteristic curve (Az) was used as the measure of
      performance. The combined radiographic index provided better results in the mild
      interstitial lung abnormality group (Az = 0.94 +/- 0.02), but it also yielded
      good results in the severe interstitial lung abnormality group (Az = 0.98 +/-
      0.01). These results indicate that this system of combining radiographic indices
      has improved the detection performance over that with our previous system.

PMID- 9165421
TI  - An evaluation of ten digital image review workstations.
AB  - A suite of performance tests are defined and performed on a total of 10 primary
      diagnostic image review workstations. System architectures, user interface, image
      manipulation tools, and data retrieval rates are discussed and analyzed.
      Performance timings are normalized to MB/sec to remove image file size
      dependencies from the data analysis. Although it is likely that some performance
      and capacity data may be dated as this article goes to press, it is hoped that
      the test definitions, methodology, and baseline data will aid those contemplating
      equipment purchases to make a more informed choice.

PMID- 9165422
TI  - Does intensity windowing improve the detection of simulated calcifications in
      dense mammograms?
AB  - This study attempts to determine whether intensity windowing (IW) improves
      detection of simulated calcifications in dense mammograms. Clusters of five
      simulated calcifications were embedded in dense mammograms digitized at 50
      microns pixels, 12 bits deep. Film images with no windowing applied were compared
      with film images with nine different window widths and levels applied. A
      simulated cluster was embedded in a realistic background of dense breast tissue,
      with the position of the cluster varied. The key variables involved in each trial
      included the position of the cluster, contrast level of the cluster, and the IW
      settings applied to the image. Combining the ten IW conditions, four contrast
      levels and four quadrant positions gave 160 combinations. The trials were
      constructed by pairing 160 combinations of key variables with 160 backgrounds.
      The entire experiment consisted of 800 trials. Twenty student observers were
      asked to detect the quadrant of the image in which the mass was located. There
      was a statistically significant improvement in detection performance for clusters
      of calcifications when the window width was set at 1024 with a level of 3328, and
      when the window width was set at 1024 with a level of 3456. The selected IW
      settings should be tested in the clinic with digital mammograms to determine
      whether calcification detection performance can be improved.

PMID- 9165423
TI  - An improved computer method to prepare 3D magnetic resonance images of thoracic
      structures.
AB  - The mediastinal and cardiovascular anatomy is complex. We have developed a three
      dimensional (3D) reconstruction system for the major mediastinal structures using
      magnetic resonance imaging data on a NeXT workstation. The program uses a
      combination of automatic and manual procedures to determine the contours of the
      cardiac structures. The geometric centers of the contours are connected by a 3D
      space curve, and the central axis of each cardiac structures is determined. The
      contours are projected on the perpendicular plane to the central axis and
      semiautomatically processed until the contours of one pixel are obtained. Then
      the surface rendering with transparency is performed. Compositing combines two
      images so that both appear in the composite, superimposed on each other.
      Demonstration of the various mediastinal lines and cardiovascular diseases by the
      composits of the partly transparent 3D images has promoted a better understanding
      of the complex mediastinal and cardiovascular anatomy and diseases.

PMID- 9165424
TI  - Urinary epidermal growth factor (EGF) levels and epidermal growth factor receptor
      (EGF-R) expression in human cerebral tumors. Clinical considerations.
AB  - The levels of Epidermal Growth Factor (EGF) in urine samples collected from 58
      patients (22 low grade gliomas, 13 anaplastic gliomas, 15 glioblastomas and 8
      meningiomas) with cerebral tumors admitted at our Institute during 1994 were
      determined. EGF levels were measured by a specific RIA method. A preoperative and
      one or two postoperative determinations were performed. Further samples were
      collected before and at three weeks after postoperative radiotherapy and/or
      chemotherapy. EGF-Receptor (EGF-R) was determined by an immunohistochemical
      method on specimens of the same tumor. Preoperative levels showed a positive
      correlation with the degree of tumor anaplasia. A decrease of the postoperative
      levels of EGF was observed in all patients who underwent surgery and the entity
      of the decrease seemed to be well correlated with the extent of the tumoral
      resection. A strict correlation between EGF levels fluctuations and clinical and
      neuroradiological features was documented in patients submitted to radiotherapy
      and/or chemotherapy. The preliminary results on EGF-R expression suggest the
      existence of a correlation between EGF levels and the receptor expression. In 4
      cases of glioblastoma low preoperative levels were associated to an high receptor
      expression in 2 cases while in the remainder the receptor was not detectable. An
      high receptor expression is pathognomonic of meningiomatous tissue, even if is
      not correlated to the biological behaviour and histological features of the
      neoplasia. These preliminary data suggest the reliability of EGF levels/EGF-R
      determination in the diagnosis and follow-up of patients with cerebral tumors
      particularly for those of glial origin. Our data confirmed the role of the EGF
      system in the development and growth of human gliomas and meningiomas.

PMID- 9165425
TI  - Results of early surgery in poor-grade aneurysm patients.
AB  - METHODS: During a 4-year-period (1991-1994) a total of 85 poor-grade [Hunt and
      Hess (H&H) IV and V] patients were treated for aneurysmal subarachnoid
      hemorrhage. Patients who were admitted in poor grades but improved after initial
      treatment were excluded from this study. RESULTS: Overall mortality was 46% (N =
      39). In particular, 29% (18 out of 63) of surgically treated patients had died as
      opposed to 95% (21 out of 22) of conservatively treated patients. Early surgery
      provided favourable (Glasgow-Outcome-Scores (GOS) 4-5) results in 52% of H&H
      grade IV patients but only in 22% of grade V patients. In particular,
      approximately one fourth of grade IV patients had a good outcome and 30% were
      only moderately disabled. Intracranial pressure (ICP) below 20 mmHg proved to be
      a favourable prognostic sign. CONCLUSIONS: It is concluded that, in consideration
      of the management mortality encountered with delayed surgery, H&H grade IV
      patients benefit from early surgical treatment while the prognosis of grade V
      patients still remains unfavourable.

PMID- 9165426
TI  - Surgical treatment of the distal anterior cerebral artery aneurysms.
AB  - A series of eleven patients with aneurysms of distal anterior cerebral artery,
      microsurgically operated and submitted to accurate neuropsychological testing, is
      reviewed. Of these, ten patients had an aneurysm at the bifurcation of distal ACA
      into pericallosal and callosomarginal branches and only one patient had an
      aneurysm at the beginning of the fronto-polar artery. All our patients were
      operated by an interhemispheric approach, that was associated in 3 cases to a
      pterional approach in order to clip a second aneurysm in other location. The
      postoperative grade was satisfactory in any of the eleven patients. The aneurysms
      of distal ACA may be surgically obliterated through a variety of approaches but
      the exposure via the interhemispheric fissure is used by many neurosurgeons. In
      our experience the interhemispheric approach allows the exposure of feeding
      artery and the control of proximal vessel without morbidity. Some authors have
      modified the interhemispheric approach to improve, in their opinion, surgical
      exposure, introducing partial resection of anterior portion of corpus callosum,
      used, by them, especially for the aneurysms just beneath the genu of corpus
      callosum. Although resection of the anterior 2.5 cm of the corpus callosum can be
      performed without causing any neurological deficit, as reported by the same
      authors, the use of this technique might not be necessary. The present paper
      deals with current surgical techniques and their modification for the treatment
      of distal anterior cerebral artery (ACA) aneurysms.

PMID- 9165427
TI  - Electrophysiological (EEG-SSEP) monitoring during middle cerebral aneurysm
      surgery.
AB  - SSEPs were monitored during 38 procedures for aneurysms of the middle cerebral
      artery. In 13 selected patients intraoperative barbiturate protection with sodium
      thiopental was performed during temporary M1 occlusion. Combined EEG monitoring,
      showing burst suppression typical pattern of electrical cortical activity, allows
      a minimal dosage (3-6.5 mg/kg) of thiopental to achieve brain protection. Any
      patient with TYPE I SSEP changes had a new postoperative neurological deficit.
      Five patients during temporary middle cerebral artery clipping showed TYPE II
      SSEP changes and only one, not achieving burst suppression EEG pattern, had
      transient postoperative neurological deficit. In two other patients, a
      progressive worsening of TYPE II SSEP was observed; this was due to excessive
      brain retraction without brain protection and had a prolonged postoperative
      neurological deficit. Four patients showed TYPE IV SSEP changes during temporary
      M1 occlusion, one of whom was a 52-year-old woman, who, in spite of brain
      protection with thiopental, had serious postoperative neurological sequelae. In
      this patient N20 amplitude and central conduction time did not have full recovery
      to the preocclusive values. This study suggests that combined
      electrophysiological monitoring may reduce complications due to excessive
      retraction of cerebral tissue, make temporary clipping safer and improve the
      results of middle cerebral artery aneurysm surgery.

PMID- 9165428
TI  - Early postoperative seizures and endovenous phenytoin. Preliminary clinical data.
AB  - Early seizures represent a major complication in the post operative course of
      patients operated on for supratentorial tumors or AVMs. The real effectiveness of
      the AEDs prophylaxis to reduce the occurrence of post operative seizures is
      controversial. We proposed a prophylactic treatment with endovenous PHT
      consisting of two infusions of PHT (mean dosage of 18 mg/kg; mean time of 1 hr)
      perioperatively and during the first postoperative day. The interruption of the
      previous oral anticonvulsant treatment is not required. The endovenous route
      should permit a rapid reach of the therapeutical range. Sixty-six patients were
      treated. Fifty-one patients received two infusions and 15 patients only one
      infusion. The serum concentration of PHT performed at 24 hrs of operation was in
      most of patients (more than 80%) in the lower part of the therapeutical range
      while at 24 hrs of the second infusion was in the higher part or over the range.
      The overall prevalence of seizures was 10.6%. In the first group the incidence
      was 7.8%, in the second one was 20%. All the seizures appeared within 48 hrs of
      the operation. All the patients in the first group had single seizures, 2
      patients of the second one experienced two seizures. No status epilepticus was
      observed. Alteration of consciousness and mild hypotension were the most common
      side effects. They never required major measurements and were mild, transient and
      completely reversible. We are starting with a randomized study based on a larger
      sample of patients which will allow a more reliable statistical analysis.

PMID- 9165430
TI  - Occult dysraphism in adulthood. A series of 24 cases.
AB  - The results of a retrospective study of 24 adult patients with occult dysraphism
      are described. There were 15 males and 9 females, with an average age of 31.1
      years. Specific circumstances precipitated symptomatic onset in 67% of patients.
      Pain, often referred to the anorectal region, was the most common presenting
      symptom. Bladder and bowel dysfunction were also common findings. The most common
      tethering lesions were intradural lipoma and a short thickened filum terminale.
      Myelography revealed the diagnosis of tethered conus in most cases, but the
      addition of CT and MRI images provided valuable structural details. The surgical
      outcome was gratifying in relation to pain and sensory-motor deficits but
      disappointing in the resolution of sphincter disorders. Our conclusion is that
      symptoms and/or signs of TCS with onset in adult life are not invariably
      irreversible.

PMID- 9165429
TI  - Alteration of complex IV and acetylcholine-related enzymes in experimental spinal
      cord injury.
AB  - Acute, severe injury of the rabbit spinal cord, induced by the weight-drop
      method, causes alterations of the enzyme activities related to cholinergic and
      energy metabolism. Morphological examinations at the trauma site show
      degenerative processes in neurons 0.5 hr posttrauma and a marked decrease in the
      number of living cells 24 hrs later. Both biochemical and cytochemical findings
      show that the tissue metabolic and morphologic derangement, caused by severe
      spinal cord injury, is mostly confined to the gray matter at an early stage (0.5
      hr), whereas 24 hrs later the white matter is also involved. The decrease in
      choline acetyl-transferase and acetylcholinesterase activities in the gray matter
      parallels the impairment of complex IV (cytochrome c oxidase) of the respiratory
      chain and the presence of morphological alteration in neurons. The dramatic drop
      in the enzyme activities, observed 24 hrs after the induction of the severe
      trauma is clearly associated with the loss of cells.

PMID- 9165431
TI  - Peritumoral subarachnoid hemorrhage in microsurgical transitional interface type
      meningioma: may the interface play a role?
AB  - The evidence of an intracranial hemorrhage from a meningioma, in comparison with
      bleeding from different intracranial tumours, is very infrequent. The
      pathophysiological mechanisms that can explain the possibility of bleeding from
      meningiomas have not been yet completely clarified. We report a case of a left
      parasagittal meningotheliomatous meningioma, situated in the premotor cortex,
      presenting with a peritumoral hemorrhage, at the interface between the meningioma
      and the brain parenchyma, and strictly confined within the subarachnoid space. A
      detailed immunohystochemical study of the tumour was performed. The
      neuroradiological and neurosurgical analysis of the tumour-to-brain interface,
      served to understand the pathophysiology of this uncommon behaviour. Other
      possible pathomechanisms explaining bleeding from meningiomas, in the light of
      the more recent literature are discussed.

PMID- 9165432
TI  - Desmoplastic non-infantile ganglioglioma.
AB  - A case of temporal desmoplatic ganglioglioma surgically removed in a 17-year-old
      patient is reported. Immunohistochemistry showed glial and neuronal
      differentiation of tumour cells. The frequent occurrence of a desmoplastic
      component in gangliogliomas is stressed. The present case and other reports from
      the literature confirm that such desmoplastic neoplasms can not be regarded as
      exclusively infantile tumours, as recently proposed by the WHO-classification of
      Brain Tumours.

PMID- 9165433
TI  - Metastatic oligodendroglioma. Case report.
AB  - We report a case of remote metastasis of oligodendroglioma. Similar cases are
      reported in the literature for malignant cerebral tumors. Our case seems rather
      different because of low grade histology. Potential malignancy was evidenced only
      by further investigations with labeling indexes.

PMID- 9165434
TI  - Fractures in children.

PMID- 9165435
TI  - Epidemiology of children's fractures.
AB  - Fractures constitute 10% to 25% of all pediatric injuries and are more common in
      boys than in girls, and after age 13 or 14 years are twice as common. The results
      from an epidemiologic study in Malmo indicate that a child's risk of sustaining a
      fracture is 42% in boys and 27% in girls from birth to age 16 years. Fractures of
      the distal end of the radius are the most common injury, followed by fractures of
      the phalanges of the hand. From 1950 to 1979 there was a twofold increase in the
      risk of fracture, due to an increase in light-energy trauma, mainly sporting
      activities. Since the end of the 1970s there has been no further increase in the
      fracture risk. The data also indicate that preventive measures have been
      effective in decreasing severe accidents.

PMID- 9165436
TI  - Periosteum: its relation to pediatric fractures.
AB  - The periosteum is an important factor for bone healing in children and plays a
      vital role for bone remodeling throughout life. Its intimate relation with the
      growth plate might influence overgrowth in children and correction of angular
      deformities. However, more research is warranted to illuminate its exact
      function.

PMID- 9165437
TI  - The triplane fracture: four years of follow-up of 21 cases and review of the
      literature.
AB  - The triplane fracture of the distal tibia consists of several anatomic types,
      including two to four principal fracture fragments. According to previous
      calculations, 7% of all ankle fractures in girls and 15% in boys birth to 18
      years old who have open growth plates are triplane fractures. In this update of a
      previous study and literature review of 209 cases (108 boys and 101 girls), the
      mean ages in boys and girls were 14.8 and 12.8 years, respectively (P < 0.00005).
      The triplane fracture did not occur in children younger than 10 and not in those
      older than 16.7 years. Thirty-five percent of the cases were treated without
      reduction, 30% with closed reduction, and 35% with open reduction. The choice of
      treatment depended on many variations in the materials reviewed. Excellent
      results were reported in 79% of 184 cases with follow-up. Neither age, sex,
      stage, nor treatment had a consistent influence on the frequency of less-than
      excellent results. There was a weak tendency to deteriorating results with time
      to follow-up (r = 0.19, P = 0.016). Inadequate reduction seemed to be an
      important factor in the few cases with fair or poor results (4.7%), even if this
      presumption could not be verified statistically.

PMID- 9165439
TI  - Supracondylar fractures: what's new?
AB  - In the past 5 to 7 years many advances have been made in the treatment of type
      III supracondylar fractures of the humerus. Gartland's three-type classification
      has continued to be used as a valuable tool to determine the aggressiveness of
      treatment. Use of cast immobilization for type III injuries has been shown to
      produce inferior results. Percutaneous pin fixation for reduced fractures has
      been established as the ideal treatment for most type III displaced fractures.
      Mediolateral or three lateral pin constructs provide the most rigid fixation. It
      is now apparent that the anterior interosseous nerve is probably the most
      commonly injured nerve. Recent technology in evaluating the vascular system has
      shown that the incidence of injuries to the brachial artery is probably higher
      than originally suspected. However, the management of these arterial injuries in
      patients who appear to have adequate profusion of the forearm musculature for
      normal function is still controversial, with recommendations varying from simple
      observation to aggressive primary arterial repair. Cubitus varus has been found
      to be due primarily to angulation in the coronal plane. Fortunately the incidence
      of complications after corrective osteotomies with this deformity has decreased
      from 50% to less than 15%. Although ipsilateral fractures are usually the result
      of greater forces of trauma, the incidence of associated neurovascular compromise
      does not appear to be any greater. Better recognition of flexion-type injuries
      has shown that the incidence is greater than originally suspected. A large
      percentage of these completely displaced flexion injuries may require open
      surgical intervention to obtain adequate reduction.

PMID- 9165438
TI  - Modern trends for external fixation of fractures in children: a critical review.
AB  - There is considerable controversy about the use of external fixation to manage
      children's fractures. The indications for external fixation are examined in the
      light of the available evidence in the literature. A general overview of surgical
      considerations, including the type of fixator, pin placement, and duration of
      treatment, is given with an assessment of possible complications. External
      fixation offers a safe and effective management option and may perhaps be the
      subject of randomized controlled trials in the future.

PMID- 9165440
TI  - Modern trends in internal fixation of femoral shaft fractures in children. A
      critical review.
AB  - Elastic intramedullary (IM) devices, which avoid the physeal region like Nancy
      and Ender nails do, can be used in children younger than even 4 years without
      compromising the trochanter physis or risking an avascular necrosis.
      Intramedullary fixation of femoral shaft fractures leads to satisfactory results
      of alignment and union. Prerequisites for intramedullary closed nailing are a
      traction table, especially for older children and adolescents, and an image
      intensifer. Interlocking IM, Ender, and Nancy nails all have the equal advantage
      of early weight bearing and reduced hospitalization time compared with traction
      and cast management. Kuntscher or interlocking nails should only be used in
      adolescents close to the end of growth to avoid growth arrest of the
      trochanterocervical physis. Kuntscher nails and interlocking IM nails are both
      associated with the small but troublesome risk of avascular necrosis. Ender and
      Nancy nails, with retrograde or antegrade pinning, have a low complication rate
      and a short learning curve for surgeons. Overgrowth in late controls after IM
      rodding of shaft fractures is about the same as the other types of treatment with
      an average overgrowth of 7 mm. Short hospital stay for children with IM nails
      reduces cost of treatment to about one half compared with in-hospital traction
      and cast management.

PMID- 9165441
TI  - Bone remodeling in malunited fractures in children. Is it reliable?
AB  - Fracture malunion is not a rare phenomenon in children due to the frequent use of
      closed reduction treatments. In this article, the processes of bone remodeling in
      cases of angular and rotational deformities, overriding of bone fragments, and
      overgrowth are addressed. Critical analyses of the mechanisms to correct these
      deformities, function of the physis and periosteum, and other related factors are
      given. The acceptable deformities for complete remodeling to be successful vary
      at different ages and locations.

PMID- 9165442
TI  - Psychosocial development and premorbid skeletal growth in Legg-Calve-Perthes
      disease: a study of nineteen patients.
AB  - We studied psychosocial development and skeletal growth in 19 newly diagnosed
      patients with Legg-Calve-Perthes disease (LCPD). Eleven patients had problems in
      visuospatial skills and five of 12 school-aged children had learning
      difficulties. The growth velocity of the patients was evaluated from 4 years
      before until 2 years after the diagnosis was made. Eight patients had a catch-up
      growth with +1.2 (0.9-1.7) delta SDS score (SDS: mean and ranges) before the
      diagnosis. Four patients with short stature and retarded bone age slightly
      diminished their growth velocity. Overnight serum growth hormone (GH)
      concentration and insulin-like growth factor I (IGF-I) levels were examined in
      the first nine consecutive patients. One patient had a high and another had a low
      mean GH concentration level, whereas all patients had IGF-I levels within normal
      limits. These results suggest that different kinds of growth disturbances may be
      associated with LCPD.

PMID- 9165443
TI  - Early innominate osteotomy as a treatment for avascular necrosis complicating
      developmental hip dysplasia.
AB  - The clinical and radiographic outcomes of 25 patients with avascular necrosis
      (AVN) of the femoral head complicating developmental hip dysplasia (DDH) were
      analyzed. Seven patients (group A) had an innominate osteotomy 1-3 years after
      the ischemic insult. Eight patients (group B) had a pelvic osteotomy between 5
      and 10 years after the insult, and 10 patients (group C) did not have a pelvic
      osteotomy. The minimum follow-up period was 10 years from the time of the
      ischemic insult. The hips in group A patients (early osteotomy) showed
      significantly better radiographic outcomes as assessed by a modified Severin
      grading. These patients also had less pain, fewer gait disturbances, and required
      fewer additional procedures for limb length discrepancy or greater trochanteric
      overgrowth.

PMID- 9165444
TI  - Natural history of distal spinal agenesis.
AB  - We studied the natural course in patients with distal spinal agenesis (DSA).
      Specifically, we compared children with different types of DSA (Renshaw sacral
      agenesis types I-IV) and determined their maximum ambulatory abilities,
      identified patients at risk for decubiti, determined the average number of
      operations per patient, described associated congenital anomalies, and sought a
      correlation between different types of DSA and the risk of back pain and
      development of scoliosis. Through a retrospective analysis, we concluded that
      there are definite correlations between the specific type DSA and the natural
      course with regard to all these entities.

PMID- 9165445
TI  - Long-term results after adolescent Blount's disease.
AB  - A long-term follow-up study was made of 23 patients with an average age of 47
      years (range 38-68 years) who had adolescent Blount's disease. Four patients had
      bilateral disease (27 affected knees). Nine knees had no treatment during
      childhood, 11 were treated by physiodesis, and seven were treated by osteotomy of
      the proximal tibia. At follow-up, most of the patients had no pain or mild pain
      from their knee. Nine knees showed arthrosis. We conclude that most children with
      adolescent Blount's disease will have a straight leg at middle age without
      arthrosis and that this result can be obtained in one of four patients without
      treatment.

PMID- 9165446
TI  - Effect of the environment on fetal skin wound healing.
AB  - Skin wound healing has been shown to be a different process in the fetus than in
      the adult animal. Some of these differences have been attributed to the unique
      fetal environment (i.e., amniotic fluid). The aim of the present study is to
      compare fetal skin healing in intraamniotic and extraamniotic wounds. A fetal
      rabbit model has been used in which three types of skin wounds were induced on 23
      day-old fetuses in contact with either amniotic fluid or maternal peritoneal
      fluid. The wounds consisted of a sutured skin incision, a nonsutured incision,
      and an electrocautery burn. Seven days later all wounds were examined
      mechanically (scar resistance), biochemically (collagen and noncollagen protein
      concentration), and histologically. Biochemical and growth factor studies of both
      environments, the amniotic and the peritoneal fluids, were also conducted. The
      results showed excellent healing by first intention and absence of healing by
      second intention in both environments, greater scar resistance in the
      intraperitoneally positioned fetal wounds, and a higher concentration of insulin
      like growth factor-1 (IGF-1) in the peritoneal fluid than in the amniotic fluid.
      It can be concluded that fetal skin wounds in contact with peritoneal fluid show
      the same healing pattern as in the natural fetal environment (amniotic fluid).
      The higher concentration of IGF-1 in the peritoneal fluid suggests that this
      growth factor, through its relationship with the growth hormone, plays a role in
      increasing the scar resistance of fetal skin wounds in contact with maternal
      peritoneal fluid.

PMID- 9165447
TI  - Immunohistochemical distribution of surfactant apoprotein-A in congenital
      diaphragmatic hernia.
AB  - The high mortality for congenital diaphragmatic hernia (CDH) has been attributed
      to a combination of pulmonary hypoplasia and persistent pulmonary hypertension.
      Recent experimental studies suggest that surfactant deficiency may also
      contribute to CDH pathophysiology. In this report, the authors
      immunohistochemically and morphometrically examined whether or not the
      hypoplastic lungs of CDH are associated with the immaturity of the surfactant
      system, especially alveolar type II cell function. Nine autopsy cases with CDH
      were immunohistochemically examined for the expression of surfactant apoprotein,
      using anti-IgG against human surfactant apoprotein A (SP-A), and the findings
      were compared with those in a gestational and postnatal age-matched control
      group. The lung/body weight ratio in the CDH was less than that in the controls
      (0.010 +/- 0.005 versus 0.021 +/- 0.013, P < .01). The radial alveolar count
      (RAC) of the CDH cases were also significantly less than that of the control
      cases (2.10 +/- 0.52 versus 3.48 +/- 0.39, P < .01). In the CDH cases, the RAC of
      the lung on the affected side were also significantly less than that of the lung
      on the unaffected side (1.71 +/- 0.34 versus 2.50 +/- 0.26, P < .01). In the
      immunohistochemical distribution of SP-A, compared with the control cases, the
      number of SP-A-positive cells on the alveolar septa of the CDH cases decreased in
      number, and this immunohistochemical reaction was weak even in positive type II
      cells. In addition, the immunoreaction observed in the alveolar type II cells of
      the unaffected side lungs in the four CDH cases was stronger than that of the
      unaffected side lungs. These results suggest that in the lungs of the CDH cases,
      especially on the affected side, there is a possible delay in both the structural
      growth and functional maturation or development of SP-A synthesis by alveolar
      type II cells, and this retardation of the functional maturation in alveolar type
      II cells is also considered to play a role in postnatal respiratory insufficiency
      in CDH patients.

PMID- 9165449
TI  - Fiberoptic localization of the upper pouch in esophageal atresia.
AB  - This report describes a technique that the authors developed as a simple, quick
      means of identifying the proximal pouch in neonates with esophageal atresia by
      fiberoptic instrumentation.

PMID- 9165448
TI  - Functional innervation of the aganglionic segment in Hirschsprung's disease--a
      comparison of the short- and long-segment type.
AB  - The authors examined the neuro-effector transmission in the aganglionic segment
      from 13 patients with Hirschsprung's disease, 10 patients had short-segment type
      and three patients had long-segment type. Circular muscle strips were prepared
      and the responses to transmural electrical field stimulation were examined using
      the isometric tension recording technique. In the ganglionic preparations from
      the short- and long-segment cases, the stimulation evoked a biphasic response
      consisting of a relaxation and an atropine-sensitive contraction. The relaxation
      was partly inhibited by N-omega-nitro-L-arginine (NNLA, a nitric oxide [NO]
      synthase inhibitor), and the effect of NNLA was abolished completely in the
      presence of L-arginine, which suggested the presence of NO-mediated inhibitory
      innervation. In the aganglionic preparations from the short-segment-type cases,
      stimulation evoked only an atropine-sensitive contraction, while in the
      aganglionic preparations from the long-segment-type cases, a weak inhibitory
      response persisted after the contractile response was abolished by atropine. This
      NO-mediated inhibitory response was frequently detected as the examined region
      approached the ganglionic segment. These results suggest that the aganglionic
      segment in the long-segment-type cases might therefore receive NO-mediated
      inhibitory input from the proximal ganglionic segment.

PMID- 9165450
TI  - A mediastinal window approach to aortopexy.
AB  - Between 1989 and 1994 six infants underwent aortopexy for symptomatic
      tracheomalacia via an anterior mediastinal window. This approach avoids a
      thoracotomy by using a small transverse incision over the second and third
      intercostal spaces followed by subchondral excision of these costal cartilages to
      expose the mediastinum. All patients had stridor and significant respiratory
      difficulty preoperatively; all experienced significant improvement in symptoms
      after aortopexy. There were no significant complications attributable to the
      procedure. The authors recommend this approach for aortopexy.

PMID- 9165451
TI  - Active collagen synthesis by pulmonary arteries in pulmonary hypertension
      complicated by congenital diaphragmatic hernia.
AB  - The high mortality rate for patients with congenital diaphragmatic hernia (CDH)
      has been attributed to pulmonary hypoplasia and persistent pulmonary hypertension
      (PPH). The factors that cause vasoconstriction and vascular remodeling in PPH are
      not fully understood. Immunohistochemistry was performed on lung tissue obtained
      from postmortem CDH patients with pulmonary hypoplasia and PPH (n = 21) using the
      following antibodies: alpha smooth muscle-actin (ASMA), transforming growth
      factor-beta (TGF-beta), isoform specific (TGF-beta 1, -beta 2, -beta 3), and M
      57. Normal lung tissues from age-matched sudden infant death syndrome patients
      (SIDS, n = 8) were obtained as controls. TGF-beta 3 immunoreactivity was observed
      in the adventitia but not in the media of pulmonary muscular arteries in patients
      with CDH. TGF-beta 1, -beta 2 immunoreactivity was either absent or faintly
      expressed in pulmonary arteries in CDH patients. No TGF-beta staining was
      observed in the pulmonary vasculature of SIDS patients. Newly synthesized
      procollagen (M-57) was easily detected in the media and adventitia in a large
      number of pulmonary arteries in all patients with CDH and in the neointima in two
      patients with long standing PPH. No M-57 staining was seen in the media of
      pulmonary arteries of the lungs of SIDS patients. These observations suggest a
      potential role of TGF-beta 3 but not TGF beta 1 or TGF beta 2 in pulmonary
      vascular remodeling and that smooth muscle cells in muscular pulmonary arteries
      are actively synthesizing collagen in patients with CDH complicated by PPH.

PMID- 9165452
TI  - Initial experience with FK506 (tacrolimus) in pediatric renal transplant
      recipients.
AB  - PURPOSE: The efficacy and safety of the new immunosuppressant agent, FK506
      (tacrolimus), was assessed in pediatric renal transplant recipients over a mean
      12-month follow-up period. METHODS: Twenty pediatric renal transplant recipients
      received oral FK506 therapy (0.3 mg/kg/d) in combination with azathioprine (1 to
      2 mg/kg/d) and low-dose prednisone as primary therapy (n = 11) or were converted
      from cyclosporine-based therapy (n = 9) for complications including cyclosporine
      toxicity (n = 2), acute refractory rejection (n = 4), and chronic rejection (n =
      3). Patients were then followed-up prospectively to evaluate effectiveness of
      therapy and complications. RESULTS: In the primary treatment group, 45% of
      patients had one or more rejection episodes. Two required OKT3 therapy (18%) for
      persistent rejection, with one (9%) graft loss at 3 months. All other episodes
      were treated effectively with FK506 dose adjustment and steroid pulses. Patient
      and graft survival was 100% and 91%, respectively, at 12 months mean follow-up.
      In the FK506 conversion group, two teenage girls with intractable acne and
      hirsutism were converted with complete resolution and no change in renal
      function. Four patients were converted for acute rejection: two who did not
      respond to steroid pulse and two who did not respond to both steroids and OKT3.
      All four grafts were salvaged (mean follow-up, 12 months; mean Creatinine [Cr],
      1.1). Three patients were converted for biopsy-proven chronic rejection at 3, 10,
      and 12 years after transplant (mean Cr, 2.4) with two of three of patients stable
      with functioning grafts at 1 year after conversion. Complications of FK506
      therapy included temporary insulin-dependent diabetes mellitus (10%),
      neurological complications (25%), renal toxicity (15%), and hypertension (85%).
      There were no cases of gastrointestinal toxicity, hepatic dysfunction,
      lymphoproliferative disorders, or life threatening viral infection. All symptoms
      of toxicity responded to dose adjustment. No patient required conversion from
      FK506 to other agents. CONCLUSION: This early experience indicates that FK506 in
      combination with low-dose steroids and azathioprine appears to provide safe and
      effective immunosuppression in the pediatric age group as a primary agent and may
      salvage grafts in patients with refractory steroid and OKT3 resistant rejection.
      Graft and patient survival is comparable to that seen with conventional
      cyclosporine-based immunosuppression.

PMID- 9165453
TI  - Evaluation of an extracorporeal membrane oxygenation system using a nonporous
      membrane oxygenator and a new method for heparin coating.
AB  - A new heparin binding method was applied to a miniature extracorporeal membrane
      oxygenation (ECMO) system with a nonporous membrane oxygenator (the priming
      volume, 45 mL; the membrane surface area, 0.4 m2; maximal flow rate, 2 L/min)
      that is resistant to plasma leakage. The authors evaluated the stability of the
      immobilized heparin in vitro and the feasibility of this system in animals.
      Samples of hollow fibers and tubing were rinsed at 40 degrees C for 4 days in
      normal saline, Ringer's lactate, and 1 mol/L NaCl solution. Heparin activities on
      hollow fibers after rinsing were 99 +/- 2.3% (mean +/- SD), 96 +/- 3.9%, and 93
      +/- 2.0% of the control in each solution, while those of the tubing were 87 +/-
      4.1%, 86 +/- 3.1%, and 76 +/- 8.6%, respectively. Veno-arterial ECMO using this
      heparin-coated system was performed on five beagles (8 to 12 kg) for 10 hours.
      Neither major thrombus formation nor plasma leakage was detected during the
      procedure in spite of a low flow rate (300 mL/min) and a reduced activated
      clotting time (mean, 128 seconds). Platelets decreased to 52% of the control (P <
      .01) at 1 hour, but no progressive decrease was seen thereafter. Antithrombin-III
      decreased (P < .01) and thrombin/antithrombin III complex increased (P < .05 at 4
      hours and P < .01 at 6, 8, and 10 hours) during bypass, but the changes of
      fibrinogen and fibrinopeptide A were not significant. Fibrinogen/fibrin
      degeneration products, fibrinopeptide B beta 15-42, and plasma-free hemoglobin
      levels did not rise significantly. O2 transfer of the oxygenators at a flow rate
      of 300 mL/min were 12.3 +/- 0.4 mL/min at 30 minutes, 14.3 +/- 1.2 mL/min at 5
      hours, and 14.7 +/- 1.7 mL/min at 10 hours (no statistical difference).
      Histological examination of the brains and the kidneys showed no evidence of
      thromboembolic sequela in any of the animals. These results suggest that this new
      system is a promising device for long-term ECMO in which the amount of systemic
      heparinization can be reduced with the minimal possibility of plasma leakage.

PMID- 9165455
TI  - Retaining extracorporeal membrane oxygenation cannulae after extracorporeal
      support in the neonate: is it safe?
AB  - The retention of extracorporeal membrane oxygenation (ECMO) cannulae of ECMO is
      discontinued was originally developed to avoid reexploration of the neck in
      patients who may require a second course of ECMO. Because of the incidence, at
      the authors' institution, of thrombi noted on the ends of retained cannulae and
      their potential to cause significant morbidity, a critical review of this
      procedure was initiated. A telephone survey of 72 Extracorporeal Life Support
      Organization (ELSO) centers was conducted, and ELSO registry forms were requested
      for patients who had their cannulae retained. Twenty-four of these centers had
      performed the procedure of retaining ECMO cannulae. There were 324 neonatal and
      pediatric patients who had their cannulae retained, with 41 patients (12%)
      requiring a second course of ECMO and 17 of 41 (41%) surviving the second course.
      Twelve of the 24 ELSO centers that retain cannulae have reported complications.
      Analyses of the patients who had their cannulae retained showed that the three
      best predictors for requiring a second course of ECMO were the diagnosis of
      congenital diaphragmatic hernia (CDH) a high oxygenation index just before the
      initiation of ECMO, and a lengthy first ECMO course. The only difference between
      the survivors and nonsurvivors of the second course of ECMO was the length of the
      first ECMO course (P < .05). Five of the 25 patients who required two courses of
      ECMO had serious complications from their retained cannulae and all were
      nonsurvivors. The authors conclude that patients with retained ECMO cannulae are
      at high risk for developing thrombi, which can lead to severe embolic events.
      Therefore, the procedure of retaining cannulae should only be used in patients at
      high risk for requiring a second course of ECMO and not for the convenience of
      surgical availability to remove the cannulae.

PMID- 9165454
TI  - Soft tissue sarcoma of the hand in children: clinical outcome and management.
AB  - Soft tissue sarcomas (STS) of the hand are rare in children and adolescents. From
      1965 through 1995, 18 children with STS of the hand were treated at our
      institution. Rhabdomyosarcoma (RMS) was diagnosed in 11 patients; alveolar
      histological results predominated (7 of 11 cases). Seven patients presented with
      metastatic disease and died 4 to 23 months (median, 9 months) from diagnosis;
      their surgical treatment comprised above-elbow amputation (n = 1), local excision
      (n = 1), and biopsy (n = 5). For the four patients who presented with localized
      RMS, surgery consisted of wide local excision (n = 1), local excision (n = 2), or
      ray amputation (n = 1). With an average follow-up of 5.5 years (range, 4 months
      to 18 years), 3 of the 11 patients diagnosed with RMS still survive (27%). The
      remaining seven patients presented with nonrhabdomyosarcomatous soft tissue
      sarcoma (NRSTS); the most common histological variants were epithelioid and
      malignant fibrous histiocytoma (two cases each). Surgical treatment for these
      patients comprised ray amputation (n = 3), wide local excision (n = 3),
      excisional biopsy (n = 1), and regional lymph node dissection (n = 3). One
      patient received adjuvant multiagent chemotherapy; three patients received
      supplemental radiotherapy. Six of the seven (85%) patients are alive with no
      evidence of disease at an average follow-up of 4.7 years (range, 6 months to 12
      years).

PMID- 9165456
TI  - Modified Boerema technique for the closure of congenital abdominal wall defects
      to prevent incisional herniation and infection.
AB  - Tension and infection often cause wound dehiscence or incisional herniation after
      the fascial closure of congenital abdominal wall defects in neonates. To overcome
      these problems, a modification of the Boerema technique (a method for repairing
      large incisional hernia in adults) was applied to repair abdominal wall defects
      in 14 neonates. The efficacy of this technique is discussed in this report.

PMID- 9165458
TI  - Anterior sagittal transanorectal approach to the urogenital sinus in
      adrenogenital syndrome: preliminary report.
AB  - In the female adrenogenital syndrome, the treatment of the urogenital sinus with
      high implanted vagina still presents a surgical challenge. The conventional
      technique (perineal vaginal pull-through) has been plagued by a high incidence of
      vaginal stenosis. A posterior sagittal transanorectal approach was proposed as an
      alternative to obtain an excellent exposure and thus an adequate mobilization of
      the vagina. But bivalving a normal rectum and anus has the potential for
      compromising bowel control and represents a bold maneuver, and the rectum and
      sphincteric mechanism must be meticulously reconstructed. In the original
      procedure a protective colostomy must be performed before the operation. To
      reduce these disadvantages, the authors made the following modifications:
      sagittal incision of only the anterior rectal wall (Anterior Sagittal
      Transanorectal Approach--ASTRA) and protective colostomy at the same time as the
      operation. In this way, maintaining the same excellent exposure and reducing the
      number of operations from three to two, we operated on 10 girls with
      adrenogenital syndrome: 4 with high, 3 with intermediate urogenital sinus, and 3
      who had previously undergone vaginal pull-through but experienced a vaginal
      retraction with severe stenosis. At the time of surgery four patients were under
      1 year (mean, 9.25 months) and six were from 2 to 11 years of age (mean, 6.5
      years). After closing the colostomy, all patients were continent in stools and
      urine, and the vagina looked normal. The authors suggest using this modified
      approach as an alternative to the conventional operation and for those patients
      in whom other techniques have failed.

PMID- 9165457
TI  - Progress in pediatric liver transplantation--the Birmingham experience.
AB  - This report describes the evolution of the Birmingham, UK experience with
      pediatric liver transplantation from 1983 to present. Two hundred liver grafts
      were placed in 168 children less than 17 years of age. The current survival rate
      exceeds 80%.

PMID- 9165459
TI  - Tissue compatibility and biodegradation of new absorbable stents for tracheal
      stabilization: an experimental study.
AB  - Newly designed absorbable stents for temporary tracheal stabilization were
      implanted into the trachea of 35 Wistar rats. The stents consisted of Vicryl
      filaments in a homogeneous PDS melt. Compatibility and biodegradation were
      investigated over a study period of up to 24 weeks. After the animals were
      killed, the trachea was examined with an optic and scanning electron microscope.
      During the first 2 weeks erosive mucosal defects appeared in the trachea, as well
      as distinct polyps of granulation tissue, focal metaplasia of the epithelium, and
      inflammatory infiltrates of the lamina propria. During the period leading to the
      sixth week, the granulations flattened and mild fibrotic alterations evolved.
      After the eighth week no stent residues could be detected, whereas only slight
      signs of chronic fibrotic inflammation persisted. No evidence for aspiration of
      foreign bodies or progressive inflammatory changes of the mediastinum was found.

PMID- 9165461
TI  - Hirschsprung's disease in Oman.
AB  - The incidence of Hirschsprung's disease (HD) was studied retrospectively in Oman
      using hospital-based data. In Oman there is a single pediatric surgery unit where
      a register has been kept from 1989 to 1994, and because all cases are referred to
      this unit, a national survey could be carried out. There were 85 children with HD
      born between 1989 and 1994, and during the period there were 261,000 livebirths
      among Omani nationals. The population frequency in Oman is 1 in 3,070
      (0.3/1,000). Eighty percent of cases presented in the first 6 months. The
      incidence in different regions and within different tribes of Oman was also
      studied. The highest frequency (1 in 1,800) is in the North Sharqiya region.
      There was not a significant seasonal influence in spite of the very high
      temperatures seen in the desert summer. The ratio of male to female cases was
      2.9:1 overall, but less for longer-segment involvement. The consanguinity rate
      (first and second cousins) was 75%, which is higher than the level of
      consanguinity in the Omani population. Down's syndrome was observed in nine cases
      (11%), and a variety of other malformations were seen, including piebaldism,
      deafness, and HD in two sibships.

PMID- 9165460
TI  - Retinoic acid-induced regulation of neuropeptide Y receptor expression and
      function in the neuroepithelioma line SK-N-MC.
AB  - Neuropeptide Y (NPY) acts through specific receptors to inhibit adenyl cyclase
      and may have a role in neuroblastomas and neuroepitheliomas (NE) as a regulator
      of cell growth and differentiation. The authors have examined the status of NPY
      receptors in the NE cell line SK-N-MC and the effect of retinoic acid (RA), a
      known differentiating agent, on their expression and function. METHODS:
      Competitive NPY binding studies were performed on normal and RA-treated cells,
      followed by Scatchard analysis. NPY receptor function in the absence of or
      following RA treatment was determined by the ability of various concentrations of
      NPY to attenuate the forskolin-stimulated accumulation of intracellular cAMP. The
      mitogenic effect of NPY was evaluated by growing normal or RA-treated cell in the
      presence of various concentrations of NPY. RESULTS: Scatchard analysis showed a
      Kd of 2.3 nmol/L and a Bmax of 91,000 receptors per cell for untreated cells. RA
      treatment decreased receptor expression to 11,700 per cell without a significant
      change in receptor affinity (3.6 nmol/L). The effect of forskolin was inhibited
      by NPY in a dose-dependent fashion in both untreated and treated cells indicating
      functional receptors in both NPY stimulates the growth of normal SK-N-MC cells.
      NPY stimulated growth was significantly attenuated after RA treatment, possibly
      as a result of decreased NPY receptor expression. CONCLUSIONS: Treatment of SK-N
      MC cells with RA, a known differentiating agent, leads to decreased expression of
      functional NPY receptors and a concomitant decrease in the mitogenic effect of
      NPY. This supports the role for NPY in the pathogenesis of NE.

PMID- 9165462
TI  - Experience with a variation of the transverse incision in chest wall deformity
      correction.
AB  - This report describes a variation of the transverse chest wall incision to
      elevate all soft tissue layers of the chest wall in one layer during repair of
      chest wall deformity in children. This is a report of an experience in 285 cases.

PMID- 9165463
TI  - A case of anterior sacral meningocele totally excised using the posterior
      sagittal approach.
AB  - Anterior sacral meningocele is a rare congenital anomaly. The authors present a
      case of anterior sacral meningocele successfully excised using the posterior
      sagittal approach. The diagnosis and treatment of this unusual anomaly are
      discussed.

PMID- 9165464
TI  - Use of Doppler ultrasonography in the evaluation of liver blood flow during silo
      reduction of a giant omphalocele.
AB  - Despite the utility of prosthetic silo reduction techniques, surgical treatment
      of giant omphaloceles containing herniated liver may result in acute compromise
      of hepatic vascular flow. The authors report a case of an infant with a giant
      omphalocele containing liver, in whom hepatic vascular compromise was suspected
      during the course of prosthetic visceral reduction. Doppler ultrasonography
      performed on the herniated liver through the prosthetic silo demonstrated
      triphasic vascular flow in the liver as well as normal hepatic venous flow and
      vena caval flow, and permitted continued gradual visceral reduction and a safe,
      delayed primary abdominal wall closure on the seventh day of life. Doppler
      ultrasonography performed through the silo may be an important diagnostic adjunct
      during the visceral reduction phase of staged abdominal wall closure in infants
      with giant omphaloceles.

PMID- 9165465
TI  - Spontaneous rupture of choledochal cyst: an unusual cause of acute abdomen in
      children.
AB  - Rupture is one of the rare complications of choledochal cysts. The cause of
      rupture is unknown in many cases and is considered to be spontaneous. Two
      patients admitted to the hospital with acute abdominal picture were initially
      thought to have postoperative abscess and appendicitis. However, the presence of
      bilelike fluid suggested a bile tract pathology, and evaluation showed rupture
      choledochal cysts. Although spontaneous rupture of a choledochal cyst is a rare
      complication, and can sometimes be the initial manifestation of a choledochal
      cyst, it should be considered in the presence of bilelike fluid and
      differentiated from spontaneous perforation of the bile tract. In spontaneous
      rupture of choledochal cyst, cystectomy, cholecystectomy, and Roux-Y
      hepaticoportoenterostomy is the treatment of choice.

PMID- 9165466
TI  - Successful bronchotracheal reconstruction in esophageal bronchus: two case
      reports.
AB  - Esophageal bronchus is the most common congenital bronchopulmonary foregut
      malformation. Current surgical treatment is resection of anomalous pulmonary
      tissue, which is often hypoplastic and destroyed by infection. The authors report
      two cases of bronchotracheal reconstruction. The diagnosis was early, before 15
      days of age. The anomalous pulmonary tissue had a pulmonary arterial supply and
      venous drainage as assessed by angiography and a good functional capacity on
      selective ventilation. Bronchotracheal anastomosis was successful in both cases:
      a right main bronchus at 25 days of age and a left main bronchus at 13 days of
      age. One child underwent reoperation 1 year later for bronchomalacia of the
      reimplanted bronchus. Both children are well with normal growth 3 and 7 years
      after surgery. Chest roentgenograms showed normal and symmetrical lung aeration.
      Tracheal reimplantation may be preferred to pulmonary resection when the
      anomalous pulmonary tissue is not destroyed. The pulmonary functional capacity is
      increased and the complications of pneumonectomy avoided.

PMID- 9165467
TI  - Anesthetic management for laparoscopic cholecystectomy in children with decreased
      myocardial function: two case reports.
AB  - This report describes the anesthetic management of two children with myocardial
      dysfunction undergoing laparoscopic cholecystectomy.

PMID- 9165468
TI  - Torsion of autotransplanted splenic tissue in Gaucher disease.
AB  - A 12-year-old girl who underwent a splenectomy followed by heterotopic splenic
      autotransplantation for treatment of hypersplenism secondary to Gaucher disease
      at the age of 3 years presented with acute lower abdominal pain. Radiological
      investigations were highly suggestive of torsion of the autotransplanted splenic
      tissue, which was confirmed during subsequent laparotomy. This is the first known
      report of torsion of autotransplanted splenic tissue.

PMID- 9165470
TI  - Juvenile granulosa cell tumor of the testis: report of two cases in newborns.
AB  - Two juvenile granulosa cell tumors in the testes of two newborns are described.
      The lesion, though rare, should be considered whenever a cystic testicular mass
      is encountered in newborns or young infants. Orchidectomy is the only treatment
      required because local recurrence or metastases have never been observed.
      Karyotyping of the patient is essential when the external genitalia are abnormal.

PMID- 9165469
TI  - Neonatal Meckel's diverticular inflammation with perforation.
AB  - Meckel's diverticulum occurs in approximately 2% of the general population and is
      usually asymptomatic. Four percent of cases will present as an acute abdomen
      caused by intestinal obstruction, gastrointestinal bleeding, and inflammation. A
      neonatal presentation of Meckel's diverticulum mimicking necrotizing
      enterocolitis is described.

PMID- 9165471
TI  - Complete separation of the testis and epididymis.
AB  - This report describes an unusual case of separation of the epididymis and testis
      in a 3-year-old boy.

PMID- 9165472
TI  - Testicular enlargement in patients with 11-hydroxylase deficiency.
AB  - Testicular nodules or tumors have been well described in patients with congenital
      adrenal hyperplasia (CAH) and usually associated with 21-hydroxylase deficiency.
      The authors report on a 11-hydroxylase--deficient patient presenting bilateral
      testicular enlargement and review the literature. Testicular biopsy was not very
      helpful to make differential diagnosis between adrenal rest hyperplasia and
      Leydig cell tumor. The size of testes regressed after steroid replacement
      therapy, and this observation was suggestive for adrenal rest hyperplasia. These
      findings suggest that bilateral testicular enlargement in patients with CAH may
      occur after excessive adrenocorticotrophic hormone stimulation of cells
      differentiated from unknown origin. Orchiectomy is not required but bilateral
      testicular biopsy must be performed.

PMID- 9165473
TI  - Pediatric sacrococcygeal chordomas: a rare tumor to be differentiated from
      sacrococcygeal teratoma.
AB  - Sacrococcygeal chordoma is a rare pediatric neoplasm that may be confused with
      the more common, and indolent, teratoma. The present report describes the
      diagnosis, treatment and early postoperative convalescence of a case of chordoma
      in an adolescent child. This case is contrasted to the sacrococcygeal teratoma, a
      familial pediatric neoplasm, and the literature is reviewed with respect to
      presentation and treatment.

PMID- 9165475
TI  - Intrascrotal epidermoid cyst with extension to the rectum wall: a case report.
AB  - An 8-year-old boy presented with an asymptomatic intrascrotal epidermoid cyst
      with extension to deeper planes. Ultrasound examination showed no involvement of
      the testes or spermatic cord. Complete excision of the lesion was performed
      transcrotally. The histological examination of the lesion showed aspects with the
      same characteristics of epidermoid cysts found in the external genitalia.

PMID- 9165474
TI  - Juvenile granulosa cell tumor of the ovary in infants: a clinicopathologic study
      of three cases and review of the literature.
AB  - The clinical and pathological features of three cases of juvenile granulosa cell
      tumors occurring in infants were studied. Precocious pseudopuberty developed in
      two patients and acute abdominal symptoms related to the rupture of the tumor
      developed in one. Surgery was the only treatment in each case and no adjuvant
      therapy was delivered. No patient experienced relapse. Histological examination
      showed a predominantly diffuse pattern with prominent luteinization. Call-Exner
      bodies were absent. Two tumors had multilocular thin walled cysts containing
      large amounts of estradiol, the third one contained rudimentary microfollicles.
      The prognosis of juvenile granulosa cell tumors in infancy appears more favorable
      than those occurring in older patients. No case of tumor recurrence has been
      reported in infancy so far. Surgery appears to be the state-of-the-art treatment
      of these tumors and additional therapy (chemotherapy or radiotherapy) must be
      discussed with caution, even in advanced stages.

PMID- 9165476
TI  - Heparin-associated thrombocytopenia and thrombosis as the cause of a fatal
      thrombus on extracorporeal membrane oxygenation.
AB  - A rare state of acquired hypercoagulability known as heparin-associated or
      heparin-induced thrombocytopenia and thrombosis (HATT, HITT) exists. It appears
      to be caused by an antibody reaction with heparin-platelet factor 4 complexes. A
      mild and severe form exist, but both varieties occur after exposure to heparin.
      The authors describe a fatal neonatal case of hypercoagulability on
      extracorporeal membrane oxygenation, and their evaluation that determined the
      etiology as type II HATT. They discuss the pathophysiology of HATT as well as
      possible alternative anticoagulation approaches.

PMID- 9165477
TI  - Concurrent left congenital diaphragmatic hernia and esophageal atresia: case
      report and review of the literature.
AB  - Coexisting congenital diaphragmatic hernia and esophageal atresia is an extremely
      rare phenomenon. Details of one infant with such a combination is presented, and
      the literature on the subject is reviewed.

PMID- 9165478
TI  - Continuous communicating esophageal and gastric duplication.
AB  - Duplications of the esophagus or stomach alone are infrequent, and complete
      foregut duplication has only rarely been described. Most combined esophagogastric
      duplications present within the first year of life, and if communication with the
      normal alimentary tract does occur, it does so only either above or below the
      diaphragm. This report illustrates a case of continuous duplication of the
      esophagus and stomach with communication to the normal alimentary tract at both
      proximal and distal ends. Operative management and a review of the literature and
      embryology are described.

PMID- 9165479
TI  - Pulmonary agenesis with intrathoracic upper limb.
AB  - A 10-week-old boy was referred because of respiratory distress, absence of right
      upper limb, and a mass in the right upper chest and shoulder region.
      Investigations showed agenesis of the right lung; the right hemithorax was filled
      by a mass that was mainly cystic but also contained a deformed right upper limb.
      When surgery was performed at the age of 13 weeks, the mass was delivered out of
      the chest and removed together with the deformed limb. The upper 5 cm of the
      shaft of the humerus could be preserved, and the chest wall could be repaired
      satisfactorily. Recovery was uneventful. The embryology of the malformation is
      briefly discussed.

PMID- 9165480
TI  - Urologic abnormalities in Menkes' kinky hair disease: report of three cases.
AB  - Menkes' kinky hair disease is a rare congenital disorder of copper metabolism
      with X-linked recessive inheritance. It is well known that it is frequently
      associated with urologic abnormalities. The authors experienced three such cases,
      but each of them was different. Multiple bladder diverticula, right vesico
      ureteral reflux, and right hydronephrosis were noted on the first baby boy. In
      the second case, hematomas in the left kidney, pelvis, ureter and the adipose
      capsule, which were thought to be the abnormality of vessels, were noted in the
      neonatal period. In the third body, multiple bladder diverticular were noted at
      the age of 1 year. One year, 10 months later, a spontaneous rupture at the huge
      diverticulum occurred.

PMID- 9165481
TI  - Hourglass thoracic lipoma of infancy: case report and review of the literature.
AB  - The authors present a case of lipoma in infancy. A 12-year-old boy was referred
      for an asymptomatic fast-growing thoracic tumor of 1-month evolution. A simple
      chest x-ray showed an intra- and extrathoracic mass of extrapleural localization.
      Ultrasound scan and computed tomography studies were performed, and the diagnosis
      of an hourglass lipoma was confirmed by a fine-needle aspiration biopsy. Surgical
      excision of the tumor was performed and the pathological study reassessed the
      initial diagnosis of lipoma. The thoracic lipoma is a benign disease and has a
      good evolution after surgery.

PMID- 9165482
TI  - Separation of thoraco-omphalopagus conjoined twins with complex hepato-biliary
      anatomy.
AB  - This report describes separation of thoraco-omphalopagus conjoined twins and
      management of the hepatobiliary complications that ensued. The livers were fused
      and, although both infants had gallbladders, the extrahepatic biliary trees were
      fused. After separation, obstructive jaundice developed in one twin and she
      required a biliary diversion. The other twin had an external biliary fistula that
      only closed after resection of a segment of liver with no connection to the
      ipsilateral biliary tree. Closure of the abdominal wall defects with
      biodegradable patches proved very satisfactory and eliminated the problems with
      persistent wound sinuses related to nonabsorbable mesh.

PMID- 9165483
TI  - Ultrastructural localization of butyrylcholinesterase in senile plaques in the
      brains of aged and Alzheimer disease patients.
AB  - Histochemical localization of butyrylcholinesterase has been carried out in
      primitive, perivascular, and classic plaques in the brains of both nondemented
      and Alzheimer disease (AD) patients. Butyrylcholinesterase histochemistry has
      been compared to amyloid beta-protein (A beta P) immunocytochemistry in adjacent
      sections. In small primitive plaques, most of the butyrylcholinesterase reaction
      product appears ultrastructurally located over plasma membranes of healthy
      looking cell processes. In more extensive primitive plaques,
      butyrylcholinesterase reaction product also decorates amyloid filaments, which
      become identifiable as delicate wisps. In classic plaques, large aggregates of
      butyrylcholinesterase reaction product colocalize with bundles of amyloid
      filaments, as well as with the compact amyloid core. Thus, deposition of
      butyrylcholinesterase in senile plaques follows a close parellelism with the
      progressive aggregation of amyloid beta-protein, supporting the possibility that
      cholinesterases may play some role in the maturation of these structures.

PMID- 9165484
TI  - 2,4-dichlorophenoxyacetic acid through lactation induces astrogliosis in rat
      brain.
AB  - Comparison of astroglial immunoreactivity in mesencephalon, cerebellum, and
      hippocampus of 25-d-old rat pups exposed to 2,4-dichlorophenoxyacetic acid (2,4
      D) through the mother's milk was made using a quantitative immunohistochemical
      analysis. A glial reaction was detected at the level of serotonergic nuclei and
      extreme astrogliosis in the hippocampus and cerebellum. A quantitative analysis
      of reactive astrocytes was performed by using GFAP and S-100 protein as specific
      markers. The study showed a significant increase in their number, size, number of
      processes, and density of immunostaining in 2,4-D-exposed animals. Exposure to
      2,4-dichlorophenoxyacetic acid on the first days of life modifies the astroglial
      cytoarchitecture in parallel to previously described neuronal changes.

PMID- 9165485
TI  - The effects of oxidative stress on in vivo brain GSH turnover in young and mature
      mice.
AB  - Glutathione (GSH) synthetase activities and GSH turnover rates were examined
      during severe oxidative stress in the mouse brain as induced by t
      butylhydroperoxide (t-BuOOH). Brain GSH synthetase activities in 8-mo-old mice in
      the cortex, striatum, thalamus, hippocampus, midbrain, and cerebellum were found
      to increase following t-BuOOH treatment. The effect of GSH synthesis on brain GSH
      turnover rates for 2- and 8-mo-old mice were determined after
      intracerebroventricular (icv) injection of [35S]cysteine. Rate constants for GSH
      turnover were determined by least-squares iterative minimization from the
      specific activity data from 20 min to 108 h after [35S]cysteine administration.
      GSH and glutathione disulfide (GSSG) specific activities were determined after
      separation by high-pressure liquid chromatography (HPLC). The half-life of GSH in
      the 2-mo-old mouse was 59.5 h and in the 8-mo-old mouse was 79.1 h. In summary,
      defense mechanisms against oxidative stress in the brain differ with age. Young
      mice can increase the cellular availability of GSH, whereas mature mice can
      increase GSH synthetase activity during oxidative stress. These differences make
      mature mice more susceptible to brain oxidative damage.

PMID- 9165486
TI  - Membrane depolarization in LA-N-1 cells. The effect of maitotoxin is Ca(2+)- and
      Na(+)-dependent.
AB  - We investigated the influence of ion compositions on the membrane potential in LA
      N-1 human neuroblastoma cells using bisoxonol as a potential-sensitive
      fluorescent dye. The ability of K+, ouabain, veratridine, and maitotoxin to
      induce membrane depolarization was evaluated. Increasing concentrations of K+
      ions from 10 to 50 mM caused a dose-dependent increase of bisoxonol fluorescence,
      which was completely independent on Na+ and Ca2+. Ouabain (5 mM), an inhibitor of
      the Na+, K(+)-ATPase, failed to induce membrane depolarization. Veratridine (40
      and 100 microM), a Na+ channel activator, only in the presence of 10 micrograms
      of Leiurus scorpion venom reduced the membrane potential. Maitotoxin (MTX) from 3
      to 10 ng/mL depolarized LA-N-1 cells in a dose-dependent manner, and produced a
      rapid and sustained increase of intracellular free calcium monitored by means of
      fluorescent probe fura-2. The MTX-induced depolarization and the increase in
      cytosolic free calcium concentration were dependent on extracellular Ca2+ ions.
      On the other hand, Na+ ions also seem to be, although only partially, implicated
      in the MTX effects, since both the blockade of tetrodotoxin (TTX)-sensitive
      voltage-operated Na+ channels and the removal of Na+ ions were able to reduce the
      depolarization. In conclusion, our data indicate that the depolarizing action of
      MTX on LA-N-1 cells is Ca(2+)- and Na(+)-dependent, although the latter only
      partially, and that this effect is dependent on Ca2+ influx into the cells likely
      through a voltage-insensitive calcium-entry system.

PMID- 9165487
TI  - Morphochemical changes in brain structures in the course of chronic haloperidol
      treatment and the correction of these changes with tuftsin.
AB  - The systemic injection of haloperidol (4 wk, 0.5 mg/kg/d) caused the increase of
      protein concentration and content, and the activity level of aminopeptidase in
      the cytoplasm of the neurons of associated type (layer III). The nucleus of these
      cells decreased both in sizes and in the content of proteins. In the neurons of
      efferent-projectory type (layer V), the decrease of studied peculiarities as
      compared with control level was observed. Tuftsin (300 micrograms/kg/d) injection
      after chronic haloperidol treatment causes the restoring action on changed
      parameters in sensomotor cortex. In caudate nucleus, tuftsin influence caused
      further reduction of neuron's cytoplasmic area and significant reduction in
      protein content. The received results testify to the morphobiochemical
      heterogenity of investigated brain structures, which is displayed both in the
      case of haloperidol treatment and in the case of its correction by neuropeptide
      tuftsin. Chronic haloperidol administration to animals can develop a model of
      certain symptoms and syndromes of parkinsonism. Its most pronounced manifestation
      is an imbalance in the neuromediator systems, especially the dopaminergic one
      (Mettler and Crandall, 1959; Colls, 1984; Funk et al., 1986). The research was
      performed in conjunction with the physiologists, whose experiments have shown
      that after chronic haloperidol administration, changes in animal behavior are
      developed that are typical for bradikinesia, and the motor regimen of integration
      is disturbed (Popova and Kachalova, 1991; Dovedova and Povova, 1993). Regulatory
      drugs, especially the tetrapeptide tuftsin, seem to correct such disturbances.

PMID- 9165488
TI  - Acrylamide and carbon disulfide treatments increase the rate of rat brain tubulin
      polymerization.
AB  - Acrylamide and carbon disulfide produce central-peripheral distal axonopathy in
      experimental animals and humans. The main feature of this disease is the focal
      swellings containing neurofilaments in distal axons, followed by nerve
      degeneration beyond these swellings. We studied the possible role of tubulin
      assembly kinetics in this disease. The rats were either administered acrylamide
      (50 mg/kg, ip, saline) or exposed to carbon disulfide (700 ppm, 9 h) via
      inhalation for 12 and 15 d, respectively. Tubulin, purified from both acrylamide
      (10.37 +/- 0.3 vs 11.3 +/- 0.15) and carbon disulfide-treated (9.72 +/- 0.5 vs
      11.18 +/- 0.25) rat brains showed increase in Vmax (OD/min x 10(3)) of its
      polymerization. However, only acrylamide treatment showed a decrease in time to
      Vmax, when brain supernatant was used for tubulin polymerization. In vitro
      addition of acrylamide (0.1-1 mM) to bovine brain tubulin also showed a decrease
      in time to Vmax (16-21%) of its polymerization. Carbon disulfide treatment of
      rats, on the other hand, showed a decrease in MAP-2 and an increase in a 120-kDa
      peptide concentration. The latter showed immunoreactivity with anti-MAP-2. The
      increase in the rate of tubulin polymerization by acrylamide and carbon disulfide
      treatment may alter the rate of transport of axonal constituents, including
      neurofilament, and contribute toward their accumulation in the focal swellings
      observed in this neuropathy.

PMID- 9165489
TI  - Retinoic acid synthesis in normal and Alzheimer diseased brain and human neural
      cells.
AB  - Retinoids play fundamental roles in CNS development, but their distribution,
      metabolism, and function within the mature human CNS are unknown. In these
      studies, extracts of autopsy tissues recovered from histopathologically confirmed
      control and Alzheimer diseased brains were tested for their ability to synthesize
      retinoic acid. Retinaldehyde dehydrogenase (RLDH), the enzyme that forms retinoic
      acid from retinaldehyde, was present in hippocampus, frontal cortex, and parietal
      cortex. The RLDH activity of hippocampus and parietal cortex from Alzheimer
      diseased brains was 1.5- to 2-fold higher (p < 0.05) compared to the controls. In
      contrast, the RLDH activity of frontal cortex was the same for both Alzheimer
      diseased and control groups. A cultured human glioblastoma (U251) and
      neuroblastoma (LA-N-5) cell line synthesized retinoic acid from retinaldehyde or
      retinol, suggesting that a variety of neural cell types possess this activity. LA
      N-5 cells grown in vitamin A-depleted medium had higher (p < 0.05) RLDH activity
      (0.35 +/- 0.04 nmol/mg/h) than LA-N-5 cells grown in vitamin A-replete media
      (0.15 +/- 0.02 nmol/mg/h). This difference was lost when retinol was added back
      to the medium, confirming that a reduction in vitamin A supply can induce RLDH
      activity in neural cells. However, this feedback mechanism does not appear to
      explain the higher RLDH activity of Alzheimer diseased hippocampus and parietal
      cortex, because the overall vitamin A status as indicated by serum retinol and
      carotenoid levels and by hippocampal retinoid content was similar for the
      Alzheimer diseased and control groups. These studies establish the presence of
      retinoids and RLDH activity in human brain tissues, and indicate that retinoic
      acid synthesis is modulated in some regions of Alzheimer diseased brain.

PMID- 9165490
TI  - The effect of postmortem delay on the distribution of microtubule-associated
      proteins tau, MAP2, and MAP5 in the rat.
AB  - Breakdown or disruption of the cytoskeleton has been implicated in the
      neurodegenerative processes of a variety of diseases, including Alzheimer disease
      (AD) and stroke. Studies of such diseases in the human involve the use of
      postmortem brain tissue. Postmortem delay may vary considerably from a few hours
      to a few days, and within this period, a degree of cytoskeletal breakdown may
      occur. It is therefore crucial to examine alterations occurring in the
      cytoskeleton as a result of postmortem delay and subtract these from those caused
      by the disease. In this study, the distribution of tau, MAP2, and MAP5
      immunohistochemistry was examined following postmortem intervals of 0-72 h in the
      rat cerebral cortex, corpus callosum, caudate nucleus, and hippocampus. Each
      microtubule-associated protein (MAP) underwent unique changes that were dependent
      both on postmortem interval and the brain region examined. Following long
      postmortem delays, some of the changes in these proteins were similar to those
      seen in rodent models of cerebral ischemia. These results demonstrate that MAPs
      are not stable during postmortem delay in the rat. Therefore, caution must be
      exercised when interpreting changes in MAPs in human postmortem tissue,
      especially in cases where ischemic injury may be involved. Examination of control
      tissue carefully matched for postmortem delay is therefore essential to allow
      meaningful interpretation of cytoskeletal abnormalities in human
      neurodegenerative disease.

PMID- 9165491
TI  - Spinal cord myelin is vulnerable to decompression.
AB  - Spinal cord white matter is the major site of tissue damage resulting from
      decompression sickness (DCS or "the bends"). Damage is thought to result from
      bubble nucleation within the tissue. Why DCS occurs predominantly in the spinal
      cord and not in the brain is not known; neither is the exact pathological
      mechanism by which the spinal cord is damaged, nor how multiple sclerosis (MS)
      like symptoms may ensue. To investigate the molecular basis of white matter
      damage, we subjected myelinated mouse tissues to varying durations of
      decompression, and then after recompression to one atmosphere, examined them for
      changes in myelin structure and composition. X-ray diffraction showed that the
      myelin period in spinal cord decreased by 4%, whereas those of optic and sciatic
      nerves were stable. The change in period was accompanied by a change in membrane
      bilayer profile--i.e., relative to control, the width of the bilayer decreased by
      approximately 6 A, whereas the interbilayer spaces each increased by
      approximately 3 A. The changes in electron density levels suggested a
      redistribution of matter from the interbilayer spaces into the lipid headgroup
      layers. By contrast with these structural changes, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and high-performance thin layer
      chromatography (HPTLC) revealed no noticeable change in myelin composition--i.e.,
      there was no release of myelin-specific proteins or lipids. Our findings indicate
      that spinal cord myelin has an inherent structural vulnerability that may
      facilitate the targeting of this tissue during pressure changes.

PMID- 9165492
TI  - Changes in brain putrescine concentration associated with nonconvulsant
      behavioral patterns induced by systemic N-methyl-D-aspartate injection.
AB  - The relationship between the behavioral effects and motor activity induced by N
      methyl-D-aspartate (NMDA) (150 mg/kg, ip) and brain polyamine concentration was
      studied in male Wistar rats. Motor activity was evaluated by an automated
      subtraction analysis system to measure the duration and vigor of any kind of
      movement. The behavioral modifications exhibited by the nonconvulsant NMDA
      treated rats were evaluated according to the composition and sequence of
      behavioral components as: hypoactivity (pattern A), partially stereotyped
      activity (pattern B), and generalized stereotyped activity (pattern C). The
      concentration of polyamines in the frontal cortex and hippocampus was measured 8
      and 24 h after drug injection. A relationship was found between the concentration
      of putrescine in both regions and the motor activity. In addition, the
      concentrations of putrescine also correlated with the vigor of the movements
      performed. Moreover, the putrescine concentration in the frontal cortex and
      hippocampus paralleled the behavioral patterns. The histological examination of
      the frontocortical and hippocampal areas did not reveal any evidence of damage.
      In conclusion, partially or generalized stereotyped activity elicited by systemic
      NMDA administration induces an increase in putrescine in the brain not linked to
      histological damage.

PMID- 9165493
TI  - Linking the family of D2 receptors to neuronal circuits in human brain: insights
      into schizophrenia.
AB  - The dopamine (DA) hypothesis of schizophrenia, which was based largely on
      evidence that pharmacological manipulations of DA systems influence the symptoms
      of schizophrenia, is undergoing a transformation due to our knowledge of the
      anatomy and pharmacology of additional subtypes of dopamine receptors. New
      research links the multiplicity of D2-like receptors to divergent neuroanatomic
      sites of suspected pathology in schizophrenia. We hypothesize that this research
      suggests that D2 receptors in the basal ganglia are the likely site of
      extrapyramidal symptoms and not antipsychotic effects. Rather, D3 receptors of
      the mesolimbic system are a likely site of antipsychotic effects, and D2 and D4
      receptors in the medial temporal lobe and limbic cortical areas are the sites of
      additional antipsychotic effects. This work also suggests that divergent DA
      receptor circuits are likely associated with the pathophysiology of this
      disorder.

PMID- 9165494
TI  - Development of the prefrontal cortex during adolescence: insights into vulnerable
      neural circuits in schizophrenia.
AB  - Multiple lines of evidence suggest that the prefrontal cortex is a site of
      dysfunction in schizophrenia. In addition, one of the characteristics of this
      disorder is the tendency for clinical symptoms to appear first during late
      adolescence or early adulthood. Recent studies in nonhuman primates have shown
      that the connectivity of the prefrontal cortex is substantially refined during
      adolescence, suggesting that these developmental changes may be critical for the
      appearance of the clinical features of schizophrenia. This article reviews data
      demonstrating that these late developmental changes are selective for particular
      neural elements in the prefrontal cortex and that they are synaptically linked.
      It is suggested that these neural elements comprise a functional circuit that is
      likely to be especially vulnerable in schizophrenia, a hypothesis that can be
      directly tested in postmortem studies.

PMID- 9165495
TI  - Gender difference in cocaine-induced HPA axis activation.
AB  - The study investigates the influence of gender on the activation of the
      hypothalamo-pituitary-adrenal (HPA) axis by cocaine and other monamine uptake
      inhibitors. Drug-induced secretion of adrenocorticotrophic hormone (ACTH) was
      used to pursue this question. Cocaine produced a dose-related rise in serum ACTH
      levels in both male and female rats, but the rise was significantly greater in
      females than in males. Females also showed enhanced HPA axis activation following
      administration of the dopamine uptake inhibitor GBR 12909, the serotonin uptake
      inhibitor fluoxetine, and the norepinephrine uptake inhibitor desipramine. No
      gender difference in HPA axis activation was observed in a dose-response study of
      cocaine-induced HPA activation in 10 day old rats. Ovariectomy of females
      decreased the ACTH response to cocaine, but castration did not affect the
      response of males. To evaluate the role of the pituitary in this gender
      difference, ACTH levels were determined after corticotropin-releasing factor
      (CRF) administration. Females showed greater ACTH responses to CRF than males.
      These studies demonstrate that female rats show exaggerated HPA responses to
      monoamine uptake inhibitors and that enhanced pituitary responsivity to CRF
      contributes to this gender difference.

PMID- 9165496
TI  - Basal and stimulated C-fos mRNA expression in the rat brain: effect of chronic
      dietary lithium.
AB  - The mechanisms underlying the therapeutic efficacy of lithium in affective
      disorders are poorly understood; however, previous studies have established an
      influence of lithium on receptor-coupled and postreceptor signal transduction
      mechanisms, including the transcription factor c-fos. We investigated the effect
      of chronic lithium on basal, stress-, muscarinic-, and haloperidol-induced c-fos
      mRNA expression in various rat brain regions. Chronic lithium produced
      significant reductions in basal c-fos expression in the frontal cortex and
      hippocampus, confirming our previous report. Stress-induced c-fos was
      significantly attenuated in the frontal cortex, hippocampus, and pituitary, was
      increased in the occipital cortex, and unchanged in the hypothalamus by chronic
      lithium. Pilocarpine-induced c-fos was significantly reduced in the frontal
      cortex and hippocampus by chronic lithium, but was enhanced in the occipital
      cortex and hypothalamus. Haloperidol-induced c-fos was augmented in the striatum
      and pituitary, but reduced in the frontal cortex by chronic lithium treatment. In
      regions in which haloperidol did not induce fos expression in control animals,
      fos levels after haloperidol were reduced after chronic lithium. One week after
      discontinuation of the lithium treatment, basal c-fos levels remained
      significantly lower in the frontal cortex and hippocampus, whereas the effects of
      stress, pilocarpine, or haloperidol on fos were normalized in most regions,
      except in the hippocampus, where the attenuated fos response to injection stress
      persisted. We suggest that repression of basal fos expression and inhibition and
      activation of inducible fos may be factors to be considered in the longer-term
      effects of lithium, leading to changes in expression of genes that regulate fos
      and are regulated by Fos, and ultimately to alterations in the functional
      activity of neural systems involved in the pathophysiology of affective disorder.

PMID- 9165497
TI  - An analysis of the effects of acute and chronic fluoxetine on extracellular
      norepinephrine in the rat hippocampus during stress.
AB  - The locus coeruleus (LC) noradrenergic system is activated by a range of arousing
      and stressful stimuli. The serotonergic inputs to this structure have been shown
      to attenuate LC activation under some conditions. The present study examined the
      effect of fluoxetine, a selective serotonin reuptake inhibitor (SSRI) known to be
      a clinically effective antidepressant, on basal and stress-induced norepinephrine
      (NE) release. Basal and stress-induced NE efflux in the rat hippocampus were
      assessed using in vivo microdialysis techniques. The effect of a 30 minute
      tailpinch stressor on extracellular concentration of NE was compared in rats
      treated with fluoxetine either once prior to tailpinch or twice daily for 14 days
      and, respectively, in unhandled controls and vehicle-treated control animals. A
      single fluoxetine injection prior to tailpinch did not significantly alter the
      tailpinch-induced increase of extracellular NE as compared to naive controls.
      However, there was an enhanced NE response to tailpinch in chronic fluoxetine
      versus chronic vehicle-treated control rats. Thus, acute blockade of 5-HT uptake
      by fluoxetine does not affect NE release in response to tailpinch stress. Chronic
      fluoxetine administration, however, results in a potentiated evoked response of
      the LC-NE system. One action of chronic fluoxetine, which may relate to
      therapeutic efficacy, is an increase in responsivity of LC neurons.

PMID- 9165498
TI  - Delta 9-tetrahydrocannabinol increases prefrontal cortical catecholaminergic
      utilization and impairs spatial working memory in the rat: blockade of
      dopaminergic effects with HA966.
AB  - The present study examined delta 9-tetrahydrocannabinol (THC)-induced alterations
      in monoamine transmission in the rat forebrain as well as the effects of the
      enantiomers of 3-amino-1-hydroxypyrrolid-2-one (HA966) on the monoamine response
      to THC. Activation of dopamine (DA) and norepinephrine (NE) but not serotonin (5
      HT) turnover in the prefrontal cortex (PFC) was observed after THC (5 mg/kg i.p.)
      administration. Both enantiomers of HA966 completely prevented the effects of THC
      on PFC DA turnover and partially blocked the THC-induced rise in NE metabolism.
      The cognitive consequences of THC exposure were also examined. THC significantly
      impaired spatial working, but not reference, memory in rats, and this effect was
      ameliorated by HA966. Thus, HA966 prevents the THC-induced increases in PFC DA
      turnover and impairments of prefrontal cortical working memory function.
      Furthermore, these data suggest that cognitive impairments displayed by marijuana
      self-administering humans may be related to PFC DA hyperactivity and that HA966
      may prevent this effect.

PMID- 9165499
TI  - Clozapine reverses the spatial working memory deficits induced by FG7142 in
      monkeys.
AB  - The atypical neuroleptic, clozapine, has been shown to have encouraging, but
      mixed, effects on prefrontal cortical (PFC) cognitive deficits in schizophrenia,
      a stress-exacerbated disorder involving dopamine (DA) dysregulation. The current
      study examined the effects of acute clozapine pretreatment on the spatial working
      memory deficits induced by the pharmacological stressor, FG7142, in monkeys.
      Previous research has shown that FG7142 impairs spatial working memory in rats
      and monkeys through excessive DA receptor stimulation in the PFC (Murphy et al.
      1996). Lower clozapine doses (1-3 mg/kg p.o.) reversed the FG7142-induced spatial
      working memory deficits, whereas doses in the clinical range (e.g., 6 mg/kg,
      p.o.) did not improve cognitive function in most animals. Clozapine alone
      produced a dose-related impairment in delayed response performance. These results
      from nonhuman primates suggest that the clozapine doses commonly used to treat
      schizophrenia may not be optimal for treating the PFC cognitive deficits
      associated with this illness.

PMID- 9165500
TI  - Hormonal therapy of breast cancer: state of the art.
AB  - Hormonal therapy has an established role in the treatment of women with
      metastatic breast cancer and also is now a major component of adjuvant systemic
      therapy for those with early-stage disease. Moreover, recent data suggest that
      hormonal agents may have a potential use in the prevention of breast cancer in
      high-risk groups. This article will provide a general overview of the current
      roles of hormonal therapy and describe future directions that show particular
      promise.

PMID- 9165501
TI  - Reliability of estrogen receptors in predicting response to antiestrogens.
AB  - In postmenopausal women, about 65% to 80% of breast cancers contain estrogen
      receptors (ERs) and 50% to 65%, progesterone receptors (PRs). Receptor-positive
      breast cancer is somewhat less common in premenopausal patients. Recently, the
      biochemical dextran-coated charcoal (DCC) assay for ERs has been replaced in many
      laboratories by immunohistochemical and immunocytochemical methods, which are not
      disturbed by endogenous estrogen or antiestrogen treatment. Receptors now can
      also be assayed from fine-needle biopsy and paraffin-embedded tissue specimens.
      The ER has been shown to be a prognostic factor for overall and disease-free
      survival in newly diagnosed and relapsed breast cancer. The value of the ER in
      predicting response to both surgical and medical endocrine treatment of breast
      cancer has been demonstrated. Ample evidence supports the predictive value of the
      ER in the treatment of breast cancer with the antiestrogen tamoxifen (Nolvadex).
      The first studies of a new antiestrogen, toremifene (Fareston), support the value
      of the ER in predicting breast cancer treatment results.

PMID- 9165502
TI  - Phase I and II studies of toremifene.
AB  - Toremifene (Fareston) is a triphenylethylene derivative structurally similar to
      tamoxifen (Nolvadex) that was selected for development based on its in vitro
      activity against breast cancer and its lesser uterotrophic effect than tamoxifen
      in rat models. In phase I and II studies conducted in several countries,
      toremifene was well tolerated over a wide range of doses (10 to 680 mg/d). The
      major side effects were hot flashes, nausea, and vomiting. Toremifene's excretion
      half-life is 5 days. It produces a modest decline in serum levels of luteinizing
      hormone, follicle-stimulating hormone, and antithrombin III, as well as an
      increase in sex hormone-binding globulin levels. In studies in which toremifene
      was used as first-line therapy in patients with estrogen receptor (ER)-positive
      or ER-unknown tumors, response rates to doses of 40 to 60 mg/day ranged from 30%
      to 54%. In two larger studies of patients who had proved refractory to tamoxifen
      therapy, toremifene produced an objective response rate of 4% to 5%. When
      patients with stable disease were added to those with objective responses, 27% to
      28% of patients were considered to derive clinical benefit from toremifene. The
      dose range chosen for further study was 40 to 60 mg/d.

PMID- 9165503
TI  - Phase III trials of toremifene vs tamoxifen.
AB  - Three pivotal phase III trials conducted in North America and Europe served as
      the basis for the application for approval of toremifene (Fareston) by the FDA.
      These trials demonstrated that 60 mg/d of toremifene is safe and effective in the
      treatment of advanced breast cancer in postmenopausal women. The studies also
      indicated that, on the basis of antitumor efficacy, as well as safety, toremifene
      is at least equivalent to tamoxifen and may have some long-term advantages.

PMID- 9165504
TI  - High-dose toremifene vs tamoxifen in postmenopausal advanced breast cancer.
AB  - To compare the efficacy and safety of high doses (200 or 240 mg/d) of toremifene
      (Fareston) to standard doses (20 or 40 mg/d) of tamoxifen (Nolvadex) in
      postmenopausal women with estrogen receptor (ER)-positive or ER-unknown advanced
      breast cancer, we pooled data from two randomized, three-arm clinical trials. Of
      the 733 patients included in the overview, 369 were randomized to high-dose
      toremifene and 364, to tamoxifen. At median follow-up of 19 months, disease had
      progressed in over 70% of the patients. Response rates were 25.2% in the high
      dose toremifene arm and 19.8% in the tamoxifen arm (P = .087). The two treatments
      appeared to be statistically equivalent with respect to risk for disease
      progression and survival. Reversible SGOT elevation was observed in 26 tamoxifen
      treated patients vs 64 high-dose toremifene recipients (P < .001) and nausea in
      33 vs 50 patients (P = .085). Reversible corneal keratopathy was diagnosed in two
      patients on tamoxifen and eight on high-dose toremifene (P = .061). Treatment had
      to be discontinued in 17.3% of patients in the high-dose toremifene arm and 20.1%
      in the tamoxifen arm. Discontinuation due to toxicity was rare, and toxicity did
      not differ significantly between the treatments. Toremifene, in doses up to 240
      mg/d, is an effective, safe treatment for postmenopausal women with ER
      positive/unknown advanced breast cancer.

PMID- 9165505
TI  - Open phase II study of high-dose toremifene as first-line therapy for advanced
      breast cancer.
AB  - In an open phase II study conducted in Finland and Latvia, 73 postmenopausal
      women were treated with 240 mg of toremifene (Fareston) as first-line therapy for
      advanced breast cancer. Among the 56 patients evaluable for responses, 59%
      achieved objective responses [complete response (CR) plus partial response (PR)],
      29% showed no change (NC), and 12% had progressive disease (PD). When all treated
      patients were included, the objective response rate was 47%. Several very long
      durations of responses up to 86 months and survival durations up to 95 months
      were observed. In assessable patients, the best objective response rates were
      seen in those with soft-tissue (74%) and visceral (60%) disease. In 54% of
      patients with very large inoperable primary cancers, a PR was achieved. Half of
      patients reported side effects, about 60% of which were mild; 30%, moderate; and
      5%, severe. Based on response rate and safety, high-dose toremifene is useful as
      first-line therapy for advanced breast cancer.

PMID- 9165506
TI  - Safety assessment of tamoxifen and toremifene.
AB  - Nonclinical and clinical safety studies on the two antiestrogens, tamoxifen
      (Nolvadex) and toremifene (Fareston), are reviewed. Tamoxifen is genotoxic,
      carcinogenic in experimental animals, and carcinogenic in humans. Toremifene has
      yielded some positive findings for genotoxicity, but was not an initiating
      carcinogen in experimental animals. Thus, toremifene has a superior nonclinical
      safety profile, although information on its long-term effects in humans is needed
      to ascertain whether its use results in improved safety.

PMID- 9165507
TI  - Evolving role of toremifene in the adjuvant setting.
AB  - The Finnish Breast Cancer Group (FBCG) started the first multicenter trial of
      toremifene (Fareston) in the adjuvant setting in 1992. The primary aim of the
      trial is to compare the efficacy and side effects of toremifene and tamoxifen
      (Nolvadex) as adjuvant therapies for postmenopausal node-positive breast cancer
      patients. About 830 patients have been enrolled in the trial to date. An interim
      analysis of the first 500 patients, performed after a mean follow-up of 18
      months, showed no significant difference between toremifene and tamoxifen with
      regard to efficacy or side effects. The study includes additional protocols aimed
      at examining some side effects, including ocular problems and the formation of
      DNA adducts in the endometrium and leukocytes, as well as possible additional
      benefits, such as effects on lipid levels and bone density. Toremifene also is
      being studied in two other trials in Europe. These studies, which are being
      coordinated by the International Breast Cancer Study Group (IBCSG), have enrolled
      approximately 600 patients to date.

PMID- 9165508
TI  - Neurophysiological assessment of brain function and maturation: I. A measure of
      brain adaptation in high risk infants.
AB  - Neurophysiologic assessments using EEG/polysomnographic studies permit the
      clinician to recognize expected patterns of brain maturation in the healthy
      neonate. By comparison, one can detect encephalopathic behaviors of newborns who
      are medically at risk. Severe physiologic expressions of encephalopathy are
      associated with neuropathologic lesions on postmortem examinations, brain lesions
      documented on neuroimaging studies, and major neurodevelopmental sequelae of
      survivors. However, such patterns are observed for only a minority of high risk
      neonates; less severe encephalopathies occur more frequently in neonates without
      evidence of brain lesions on imaging studies who either recover from medical
      illness or who manifest no findings of neurological dysfunction. These subtle and
      persistent brain disorders are obviously more difficult to detect and grade. This
      is specifically relevant for preterm infants in whom various degrees of
      encephalopathy may exist, but whose physiologic behaviors must be distinguished
      form expected behavioral and neurophysiologic patterns of prematurity. Neonates
      may express brain dysfunction as altered rates of brain maturation, as compared
      with expected patterns for a given conceptional age. Neurophysiologic expressions
      of brain dysmaturity, either from prenatal and/or postnatal stresses, may
      actually occur in a substantially larger segment of the high risk neonatal
      population than has been anticipated. EEG-sleep studies can serve as a
      noninvasive neurophysiologic probe of brain organization and maturation to extend
      clinical observations to assess the severity and persistence of brain dysfunction
      in a neonate who may be at risk for later neurodevelopmental compromise.

PMID- 9165509
TI  - Prospective, open-label, add-on study of lamotrigine in 56 children with
      intractable generalized epilepsy.
AB  - The role of lamotrigine (LTG) in childhood epilepsy is emerging. We evaluated the
      efficacy and adverse effects of LTG in an open, prospective study of 56 children
      with generalized epilepsies. Six (11%) children became seizure-free, and 24 (43%)
      had greater than 50% reduction in seizure frequency. LTG was effective against a
      broad range of generalized seizure types. Three of 15 patients with Lennox
      Gastaut syndrome achieved complete seizure control and eight demonstrated 50 to
      99% improvement in seizure control. Increase in seizures (7) and rash (5) were
      the most common side effects. After valproate was discontinued, LTG therapy was
      resumed, with no recurrence of rash in any patient. This study suggests that LTG
      may be a useful drug in the treatment of generalized epilepsies in children.

PMID- 9165510
TI  - Evoked potential abnormalities in postoperative patients with biliary atresia.
AB  - The somatosensory evoked potentials from the lower extremities were measured
      postoperatively in 15 patients with biliary atresia to investigate whether they
      were free of neurologic dysfunction. Because long-standing cholestasis causes
      progressive neuropathy due to malabsorption of vitamin E, the serum vitamin E, D,
      and A levels were also examined to evaluate the fat-soluble vitamin status. The
      cerebral evoked potentials to posterior tibial nerve stimulation were recorded in
      all 15 patients as well as in 45 controls, but spinal evoked potentials examined
      at the level of the cauda equina could not be recorded in five patients more than
      8 years of age with long-standing icterus. The remaining 10 patients exhibited
      spinal evoked potentials as observed in the controls, but the mean neural
      conduction velocity at the cauda equina was significantly lower than that of the
      45 controls (42.0 +/- 5.1 m/s vs 52.3 +/- 6.8 m/s, P = .0002). The serum vitamin
      E, D, and A levels were within the normal range in 13, 9, and 1 of 15 patients,
      respectively. These results suggest that the patients with long-term follow-up
      are still at risk of developing neural disturbances even with normal serum
      vitamin E status.

PMID- 9165511
TI  - Focal features in West syndrome indicating candidacy for surgery.
AB  - A subgroup of patients with West syndrome (WS) also have focal features, and some
      of these patients respond to surgical intervention. To determine the incidence of
      focal features in patients with WS and to establish the correlation of these
      features with outcome, all patients with WS treated in the Epilepsy Unit of the
      Children's Hospital (Boston, MA) during the years 1989 to 1992 were
      retrospectively evaluated. Focal features included partial seizures, hemiparesis,
      focal radiologic findings, asymmetric spasms, and lateralized hypsarrhythmia. The
      different focal features were later correlated with the natural history of the
      disease. Sixty-seven patients were included in the study. Sixty-six percent had
      asymmetric manifestations. Asymmetric spasms, hemihypsarrhythmia, and partial
      seizures combined with infantile spasms had significant association with
      asymmetric brain pathology. Focal features did not correlate with age of onset
      and outcome, but were associated with etiology. Eight of the nine patients who
      underwent epilepsy surgery had at least two focal features or more. Two of the
      operated children had focal features in the absence of magnetic resonance imaging
      abnormalities, thus indicating the necessity for positron emission tomography,
      the results of which justified surgery.

PMID- 9165513
TI  - Infantile spasms: seasonal onset differences and zeitgebers.
AB  - The health records of 76 infants with infantile spasms (IS) were reviewed
      retrospectively. The distribution of seizure onset was examined with respect to
      calendar month, annual changes in day length (photoperiod), and global solar
      radiation (GSR). IS onset was more frequent during the months with low GSR and
      short photoperiods. The greatest frequency of IS onset was in December and
      January (22 cases, 29%); the lowest was in April and May (8 cases, 10.5%). IS
      onset frequency (f) was more than twice as great in the months with a short
      photoperiod (10Light-14Dark) and a low GSR (f = 11) as compared with months with
      a long photoperiod (16Light-8Dark) and a high GSR (f = 5). IS onset frequency was
      2.2-fold greater in months with a short photoperiod and a low GSR. This finding
      suggests that environmental photoperiodic factors (zeitgebers) may play a role in
      the onset of IS.

PMID- 9165512
TI  - Cerebellar mutism in children: report of six cases and potential mechanisms.
AB  - Cerebellar mutism is a rare finding associated with resection of posterior fossa
      tumors or cerebellar hemorrhages. We reviewed the medical records of six
      children, aged 6 to 12 years, who developed cerebellar mutism after resection of
      a posterior fossa mass or as a result of posterior fossa trauma. From 1989 to
      1994, 210 children underwent posterior fossa resection at our institution, and
      four developed mutism (an incidence of 1.6%). All four patients had primitive
      neuroectodermal tumors. The fifth patient experienced trauma, and another patient
      had an arteriovenous malformation (AVM). In four children, hydrocephalus
      developed as a result of their tumor or AVM. Four developed cerebellar mutism 24
      to 48 hours after surgery or trauma, and one developed cerebellar mutism 5 days
      after surgery, coincident with hydrocephalus. In one, mutism occurred after a
      second resection was performed for a recurrence of his posterior fossa tumor.
      Cerebellar mutism lasted 10 days in one patient and 2 to 8 weeks in the other
      four. Dysarthria was apparent in four patients during the recovery phase. We
      suggest trauma to the dentate nucleus and/or its outflow tract, the superior
      cerebellar peduncle, as a cause of reversible mutism. Because posterior fossa
      tumors are common in children, mutism should be recognized as an important side
      effect of surgery.

PMID- 9165514
TI  - Outcome of neonates with electrographically identified seizures, or at risk of
      seizures.
AB  - A prospective study was conducted to investigate survival at 1 month and survival
      and developmental outcome at 1 year in a cohort of 53 neonates either suspected
      of or at risk of having seizures. For all patients, presence of seizures,
      diagnoses, and structural abnormalities were identified. If seizures were
      present, seizure variables were quantified. Correlations between neonatal
      parameters and subsequent outcome were investigated. Forty-three patients
      survived the first month of life. Background EEG was the only significant
      predictor of survival at 1 month. Three patients died after 1 month, and 2 of the
      three had extremely depressed interictal EEGs. Development outcome at 1 year was
      determined for all available surviving patients. Abnormal findings from brain
      imaging studies and number of independent electrographic seizure foci were
      correlated with some aspects of outcome at 1 year. No other correlations were
      identified between neonatal parameters and outcome.

PMID- 9165515
TI  - Abnormal myelination in peroxisomal isolated dihydroxyacetonephosphate
      acyltransferase deficiency.
AB  - The cranial magnetic resonance imaging findings in three siblings with
      nonrhizomelic chondrodysplasia punctata due to isolated dihydroxyacetonephosphate
      acyltransferase (DHAP-AT) deficiency are reported. Areas of high signal intensity
      in a patchy distribution on the T2-weighted images were detected in the centrum
      semiovale in the eldest patient (a 6-year-old girl). The white matter of the
      second child (a 5-year-old boy) was spared, whereas the youngest sibling (a 2
      year-old boy) manifested very severe white matter abnormalities. DHAP-AT
      catalyzes the first step in the synthesis of plasmalogens, which are major
      constituents of myelin. Defective plasmalogen synthesis may have contributed to
      abnormal myelin formation in 2 patients. Because the clinical presentation of the
      child without detectable defect in myelination was similar to that of his
      siblings, the neurologic signs observed in isolated DHAP-AT deficiency cannot be
      attributed solely to the disturbances in the myelin formation.

PMID- 9165516
TI  - Moebius syndrome and central respiratory dysfunction.
AB  - Two infants, 18 months and 4 months of age, who were born with bilateral VI and
      VII nerve palsy (Moebius syndrome) experienced central respiratory failure
      requiring persistent ventilation. The computed tomography scan showed small
      brainstem tegmental calcifications. These findings suggest intrauterine brainstem
      necrosis including the respiratory center and poor prognosis for independent
      respiration.

PMID- 9165517
TI  - Encephalomyelitis subsequent to mycoplasma infection with elevated serum anti-Gal
      C antibody.
AB  - We report a 7-year-old girl with acute disseminated encephalomyelitis subsequent
      to a mycoplasma infection. She manifested a prolonged state of akinetic mutism,
      during which EEG revealed well-synchronized spindles. Four months later, she
      regained consciousness, with no mental deficit, but complete flaccid quadriplegia
      persisted and magnetic resonance imaging disclosed extensive destruction of the
      spinal cord. Antibody against galactocerebroside was detected in her serum during
      the acute phase. The anti-Gal C antibody is suggested to be involved in the
      pathogenesis of immune-mediated demyelinating diseases in the central nervous
      system subsequent to mycoplasma infections.

PMID- 9165518
TI  - Unexpected recovery in a newborn with severe hypomyelinating neuropathy.
AB  - We report the case of a severely hypotonic and weak term newborn who required
      ventilatory support from the time of birth. Serial neurophysiologic studies were
      consistent with severe demyelinating polyneuropathy. The infant's condition
      deteriorated over several weeks despite treatment with corticosteroids and
      intravenous immunoglobulin (IVIG) for presumed inflammatory demyelinating
      polyneuropathy. Histopathologic findings in a sural nerve biopsy, however, were
      similar to those previously reported in congenital hypomyelinating neuropathies.
      After 12 weeks of hospitalization and after discontinuation of corticosteroids,
      the patient began to recover and required no further ventilatory support.
      Remarkable improvement has continued for 18 months. This patient raises questions
      about the underlying mechanisms of hypomyelinating neuropathies in early infancy.

PMID- 9165519
TI  - Bilateral tonic-clonic epileptic seizures in non-benign familial neonatal
      convulsions.
AB  - We report an electroclinical pattern considered characteristic of benign familial
      neonatal convulsions (BFNC) in two neonates without BFNC. Both neonates were
      products of uncomplicated pregnancies, labor, and deliveries. The cause of the
      seizures was not established. There was no family history of seizures or
      epilepsy. Seizures started on the second and third days after birth. Ten seizures
      were captured by continuous video-EEG telemetry. The electroclinical events began
      with generalized tonic posturing coinciding with the appearance of diffuse
      attenuation of the EEG activity. After several seconds, bilateral clonic
      movements accompanied by bilateral repetitive sharp waves or spikes occurred in
      the EEG. One patient had normal development; the other became autistic. We
      conclude that the electroclinical pattern occurring in BFNC can occur in other
      types of neonatal seizures.

PMID- 9165520
TI  - First U.S. case of adenylosuccinate lyase deficiency with severe hypotonia.
AB  - Adenylosuccinate lyase (ASL) deficiency is a defect in purine de novo synthesis
      pathway. The disease has variable clinical presentation involving psychomotor
      retardation, seizures, hypotonia, and autism. The presence of succinyladenosine
      and succinylaminoimidazole carboxamide riboside (SAICA riboside) in body fluids
      characterizes the biochemical phenotype. All cases of ASL deficiency described to
      date have been diagnosed in Europe. Using a high-resolution thin-layer
      chromatography (TLC) technique combining screening for ASL deficiency and
      disorders of saccharide metabolism, we found the first case of this disease in
      the US. The patient presented with delayed motor development and profound
      hypotonia. The family history and routine laboratory tests were negative.
      Screening for metabolic disorders detected the presence of succinyladenosine and
      SAICA riboside in urine. The activity of ASL in the patient's skin fibroblasts
      was 43% of controls (patient, mean = 1.20 nmol/min/mg of protein, s = 0.21, n =
      3; controls, mean = 2.78 nmol/min/mig of protein, s = 0.61, n = 7). In a 15-month
      old girl with profound hypotonia, we established the diagnosis of ASL deficiency
      by demonstrating succinyladenosine and SAICA riboside in urine and decreased
      residual activity of ASL in skin fibroblasts.

PMID- 9165521
TI  - Noonan syndrome and moyamoya.
AB  - We report a patient with Noonan syndrome and asymptomatic cardiac disease
      (supravalvular aortic stenosis and pulmonary valvular stenosis) who had frequent
      transient ischemic attacks. Bilateral moyamoya was evident; in addition, he
      manifested activated protein C resistance and was heterozygous for the factor V
      Leiden mutation. Anticoagulation abolished his episodes and, despite extensive
      cerebrovascular disease, he has no permanent neurologic deficits. The association
      between Noonan syndrome and moyamoya has not previously been described.
      Disruption of vascular development in prenatal life may have resulted in both
      cardiac and cerebrovascular disease in this child.

PMID- 9165522
TI  - Postural stability by computerized posturography in minor head trauma.

PMID- 9165523
TI  - Are graduate programs training pharmaceutical scientists to function effectively
      in the new, highly integrated and globalized pharmaceutical industry?

PMID- 9165525
TI  - Polar molecular surface properties predict the intestinal absorption of drugs in
      humans.
AB  - PURPOSE: A theoretical method has been devised for prediction of drug absorption
      after oral administration to humans. METHODS: Twenty structurally diverse model
      drugs, ranging from 0.3 to 100% absorbed, were investigated. The compounds also
      displayed diversity in physicochemical properties such as lipophilicity, hydrogen
      bonding potential and molecular size. The dynamic molecular surface properties of
      the compounds were calculated, taking into account their three-dimensional shape
      and flexibility. RESULTS: An excellent sigmoidal relationship was established
      between the absorbed fraction after oral administration to humans (FA) and the
      dynamic polar molecular surface area (PSAd) (r2 = 0.94). The relationship was
      stronger than those obtained for more established predictors of drug absorption.
      Drugs that are completely absorbed (FA > 90%) had a PSAd < or = 60 A2 while drugs
      that are < 10% absorbed had a PSAd > or = 140 A2. CONCLUSIONS: The results
      indicate that PSAd can be used to differentiate poorly absorbed drugs at an early
      stage of the drug discovery process.

PMID- 9165524
TI  - Cyclodextrins: their future in drug formulation and delivery.
AB  - Since their discovery, cyclodextrins and their ability to form inclusion
      complexes have fascinated chemists, formulators and recently, entrepreneurs. This
      mini-review has as its objective, a critical assessment of the current status of
      cyclodextrins in the formulation and delivery of pharmaceuticals and commentary
      on their potential future uses. The emphasis will be on answers to common
      questions often asked of pharmaceutical scientists working in this area. Why use
      cyclodextrins for drug solubilization and stabilization when alternative
      techniques are available? Why the greater interest in modified cyclodextrins and
      not the parent cyclodextrins? If a drug forms a strong cyclodextrin inclusion
      complex, how is the drug released in vivo? Dose the injection of a
      cyclodextrin/drug complex alter the pharmacokinetics of the drug? Are there drug
      products on the market which contain cyclodextrins? What is the regulatory status
      of cyclodextrins? Although definitive answers to all these questions are not
      possible at this time, many of these questions are answerable, and educated and
      informed responses are possible for the rest.

PMID- 9165527
TI  - Thermophysical properties of trehalose and its concentrated aqueous solutions.
AB  - PURPOSE: To address the lack of fundamental thermophysical data for trehalose and
      its aqueous systems by measuring equilibrium and non-equilibrium properties of
      such systems. METHODS/RESULTS: Differential scanning calorimetry (DSC) and
      dynamic mechanical analysis were used to measure glass transition temperatures of
      trehalose and its solutions. X-ray diffractometry was used to verify the
      structure of amorphous trehalose. Controlled-stress rheometry was used to measure
      viscosity of several aqueous trehalose systems at ambient and sub-ambient
      temperatures. Over this temperature range, the density of these solutions was
      also measured with a vibrating tube densimeter. The equilibrium phase diagram of
      aqueous trehalose was determined by measuring the solubility and freezing point
      depression. CONCLUSIONS: Our solubility measurements, which have allowed long
      times for attainment of chemical equilibrium, are substantially different from
      those reported earlier that used different techniques. Our measurements of the
      glass transition temperature of trehalose are higher than reported values. A
      simple model for the glass transition is presented to describe our experimental
      observations.

PMID- 9165526
TI  - Intestinal absorption screening of mixtures from combinatorial libraries in the
      Caco-2 model.
AB  - PURPOSE: Understanding how chemical structures influence transport across the
      intestinal mucosa will greatly enhance the discovery of orally available drugs.
      In an attempt to accelerate defining such relationships between structure and
      transport, six arbitrary mixtures of N-substituted glycine (NSG) peptoids
      containing 24 physicochemically diverse compounds were evaluated in the Caco-2
      model of intestinal absorption. METHODS: Samples were analyzed by HPLC and the
      areas of the peaks representing the components of each mixture were summed to
      measure "aggregate" apparent permeability coefficients (Papp), a score of the
      influence of the common structural element within each mixture towards
      absorption. Mass spectrometry was used to identify the chemical structure of Caco
      2 permeable compounds. RESULTS: Three linear trimeric mixtures were examined and,
      for each mixture, none of the components was detected in receiver chambers. It
      was concluded that the components of these mixtures each had a Papp value less
      than 0.8 x 10(-6) cm/sec, a permeability less than mannitol. Three dimeric
      mixtures were examined and they exhibited aggregate P(app) values of 9.2 x 10(
      6), 14 x 10(-6) and 6.9 x 10(-6) cm/sec. These transport rates reflected the
      transport of most of the components of each mixture. Furthermore, the components
      of the dimeric mixtures which were transported at a rate greater than mannitol
      were apparently transported by passive mechanisms. CONCLUSIONS: This study
      demonstrated that mixtures can be used to study structure-transport relationships
      in the Caco-2 model. The information obtained from this type of study will be
      integrated into the design of future chemical libraries. Other potential uses of
      chemical mixtures with the Caco-2 model are also discussed.

PMID- 9165528
TI  - Effect of glass transition temperature on the stability of lyophilized
      formulations containing a chimeric therapeutic monoclonal antibody.
AB  - PURPOSE: The purpose of this study is to highlight the importance of knowing the
      glass transition temperature, Tg, of a lyophilized amorphous solid composed
      primarily of a sugar and a protein in the interpretation of accelerated stability
      data. METHODS: Glass transition temperatures were measured using DSC and
      dielectric relaxation spectroscopy. Aggregation of protein in the solid state was
      monitored using size-exclusion chromatography. RESULTS: Sucrose formulation (Tg
      approximately 59 degrees C) when stored at 60 degrees C was found to undergo
      significant aggregation, while the trehalose formulation (Tg approximately 80
      degrees C) was stable at 60 degrees C. The instability observed with sucrose
      formulation at 60 degrees C can be attributed to its Tg (approximately 59 degrees
      C) being close to the testing temperature. Increase in the protein/sugar ratio
      was found to increase the Tgs of the formulations containing sucrose or
      trehalose, but to different degrees. CONCLUSIONS: Since the formulations exist in
      glassy state during their shelf-life, accelerated stability data generated in the
      glassy state (40 degrees C) is perhaps a better predictor of the relative
      stability of formulations than the data generated at a higher temperature (60
      degrees C) where one formulation is in the glassy state while the other is near
      or above its Tg.

PMID- 9165529
TI  - The relationship between protein aggregation and molecular mobility below the
      glass transition temperature of lyophilized formulations containing a monoclonal
      antibody.
AB  - PURPOSE: To find out if the physical instability of a lyophilized dosage form is
      related to molecular mobility below the glass transition temperature. Further, to
      explore if the stability data generated at temperatures below the glass
      transition temperature can be used to predict the stability of a lyophilized
      solid under recommended storage conditions. METHODS: The temperature dependence
      of relaxation time constant, tau, was obtained for sucrose and trehalose
      formulations of the monoclonal antibody (5 mg protein/vial) from enthalpy
      relaxation studies using differential scanning calorimetry. The non
      exponentiality parameter, beta, in the relaxation behavior was also obtained
      using dielectric relaxation spectroscopy. RESULTS: For both sucrose and trehalose
      formulations, the variation in tau with temperature could be fitted Vogel-Tammann
      Fulcher (VTF) equation. The two formulations exhibited difference sensitivities
      to temperature. Sucrose formulation was more fragile and exhibited a stronger non
      Arrhenius behavior compared to trehalose formulation below glass transition. Both
      formulations exhibited < 2% aggregation at t/tau values < 10, where t is the time
      of storage. CONCLUSIONS: Since the relaxation times for sucrose and trehalose
      formulations at 5 degrees C are on the order of 10(8) and 10(6) hrs, it is likely
      that both formulations would undergo very little (< 2%) aggregation in a
      practical time scale under refrigerated conditions.

PMID- 9165530
TI  - Differential molar heat capacities to test ideal solubility estimations.
AB  - PURPOSE: Calculation of the ideal solubility of a crystalline solute in a liquid
      solvent requires knowledge of the difference in the molar heat capacity at
      constant pressure of the solid and the supercooled liquid forms of the solute,
      delta Cp. Since this parameter is not usually known, two assumptions have been
      used to simplify the expression. The first is that delta Cp can be considered
      equal to zero; the alternate assumption is that the molar entropy of fusion,
      delta Sf, is an estimate of delta Cp. Reports claiming the superiority of one
      assumption over the other, on the basis of calculations done using experimentally
      determined parameters, have appeared in the literature. The validity of the
      assumptions in predicting the ideal solubility of five structurally unrelated
      compounds of pharmaceutical interest, with melting points in the range 420 to 470
      K, was evaluated in this study. METHODS: Solid and liquid heat capacities of each
      compound near its melting point were determined using differential scanning
      calorimetry. Linear equations describing the heat capacities were extrapolated to
      the melting point to generate the differential molar heat capacity. RESULTS:
      Linear data were obtained for both crystal and liquid heat capacities of sample
      and test compounds. For each sample, ideal solubility at 298 K was calculated and
      compared to the two estimates generated using literature equations based on the
      differential molar heat capacity assumptions. CONCLUSIONS: For the compounds
      studied, delta Cp was not negligible and was closer to delta Sf than to zero.
      However, neither of the two assumptions was valid for accurately estimating the
      ideal solubility as given by the full equation.

PMID- 9165531
TI  - Solvent effects on the solubility and physical stability of human insulin-like
      growth factor I.
AB  - PURPOSE: The solubility and physical stability of human Insulin-like Growth
      Factor I (hIGF-I) were studied in aqueous solutions with different excipients.
      METHODS: The solubility of hIGF-I was determined by UV-absorption and
      quantification of light blocking particles. The physical stability of hIGF-I was
      studied with differential scanning calorimetry (DSC) and circular dichroism (CD)
      spectroscopy. RESULTS: Human IGF-I precipitated at low temperature in the
      presence of 140 mM benzyl alcohol and 145 mM sodium chloride. CD data showed that
      the tertiary structure of hIGF-I during these conditions was perturbed compared
      to that in 5 mM phosphate buffer. In the presence of benzyl alcohol 290 mM
      mannitol stabilized hIGF-I. Sodium chloride or mannitol by themselves had no
      effect on either the solubility or the tertiary structure. Benzyl alcohol was
      attracted to hIGF-I, whereas sodium chloride was preferentially excluded. The
      attraction of benzyl alcohol was reinforced by sodium chloride leading to salting
      out of hIGF-I. The CD-data indicated interactions of benzyl alcohol with
      phenylalanine in hIGF-I. Thermal denaturation of hIGF-I occurred in all solutions
      with sodium chloride, whereas mannitol or benzyl alcohol had no effect on the
      thermal stability. The thermal stability of hIGF-I was thus decreased in 145 mM
      sodium chloride although it was excluded from hIGF-I. CONCLUSIONS: The self
      association and thermal aggregation of hIGF-I is driven by hydrophobic
      interactions. Benzyl alcohol is attracted to hIGF-I and induces changes in the
      tertiary structure causing hydrophobic attraction of the protein at low
      temperatures.

PMID- 9165532
TI  - Enhanced oral uptake of tomato lectin-conjugated nanoparticles in the rat.
AB  - PURPOSE: To investigate the usefulness of a surface-conjugated, bioadhesive
      molecule, tomato lectin, to augment intestinal uptake of orally administered
      inert nanoparticles. METHODS: Fluorescent 500 nm polystyrene nanoparticles with
      tomato lectin covalently surface coupled using a carbodiimide reaction were
      administered to female Wistar rats by oral gavage daily for 5 days. RESULTS:
      Analysis of tissue extracted polymer by gel permeation chromatography revealed a
      23% systemic uptake of tomato lectin conjugated nanoparticles compared to < 0.5%
      of TL nanoparticles blocked with N-acetylchitotetraose thus representing an
      increase of almost 50 fold across the intestine. Intestinal uptake of tomato
      lectin-conjugated nanoparticles via the villous tissue was 15 times higher than
      uptake by the gut-associated lymphoid tissue. CONCLUSIONS: The application of
      tomato lectin as a bioadhesive agent in vivo has been demonstrated to enhance
      subsequent intestinal transcytosis of colloidal particulates to which it is
      bound.

PMID- 9165533
TI  - N-acyl-(alpha, gamma diaminobutyric acid)n hydrazide as an efficient gene
      transfer vector in mammalian cells in culture.
AB  - PURPOSE: This study investigates the structure/activity relationship of a series
      of N-acyl-peptides (lipopeptides) for the transfection of mammalian cells.
      METHODS: Lipopeptides comprising 1 to 3 basic amino-acids and a single fatty acid
      chain were synthesized. Transfecting complexes between lipopeptide, plasmid DNA
      and dioleoyl phosphatidylethanolamine were prepared and applied on cells in
      culture. Transfection efficiency was evaluated by measuring beta-galactosidase
      activity 48 h post-transfection. Lipopeptide-DNA binding was also investigated by
      physical means and molecular modelling. RESULTS: Besides the length of the fatty
      acid chain, the nature of the basic amino-acid and the C-terminal group were
      crucial parameters for high transfection efficiency. The N-acyl-(diaminobutyric
      acid)n derivatives were the most potent transfecting agents among those tested
      and induced a beta-galactosidase activity 2 to 20 times higher than the N-acyl
      lysine, -ornithine or -diaminopropionic acid derivatives. Furthermore, a
      hydrazide C-terminal modification greatly enhanced transfection efficiency for
      all compounds tested. The reason why alpha, gamma-diaminobutyric acid hydrazide
      based lipopeptides were the most potent in transfection is not fully understood
      but could be related to their high DNA binding. CONCLUSIONS: Poly- or oligo
      diaminobutyric acid containing or not a hydrazide C-terminus could advantageously
      be used in peptide-based gene delivery systems.

PMID- 9165535
TI  - Confocal laser scanning microscopic visualization of the transport of dextrans
      after nasal administration to rats: effects of absorption enhancers.
AB  - PURPOSE: To visualize the transport pathway(s) of high molecular weight model
      compounds across rat nasal epithelium in vivo using confocal laser scanning
      microscopy. Furthermore, the influence of nasal absorption enhancers (randomly
      methylated beta-cyclodextrin and sodium taurodihydrofusidate) on this transport
      was studied. METHODS: Fluorescein isothiocyanate (FITC)-labelled dextrans with a
      molecular weight of 3,000 or 10,000 Da were administered intranasally to rats.
      Fifteen minutes after administration the tissue was fixed with Bouin. The nasal
      septum was surgically removed and stained with Evans Blue protein stain or
      DiIC18(5) lipid stain prior to visualization with the confocal laser scanning
      microscope. RESULTS: Transport of FITC-dextran 3,000 across nasal epithelium
      occurred via the paracellular pathway. Endocytosis of FITC-dextran 3,000 was also
      shown. In the presence of randomly methylated beta-cyclodextrin 2% (w/v) similar
      transport pathways for FITC-dextran 3,000 were observed. With sodium
      taurodihydrofusidate 1% (w/v) the transport route was also paracellular with
      endocytosis, but cells were swollen and mucus was extruded into the nasal cavity.
      For FITC-dextran 10,000 hardly any transport was observed without enhancer, or
      after co-administration with randomly methylated beta-cyclodextrin 2% (w/v). Co
      administration with sodium taurodihydrofusidate 1% (w/v) resulted in paracellular
      transport of FITC-dextran 10,000, but morphological changes, i.e. swelling of
      cells and mucus extrusion, were observed. CONCLUSIONS: Confocal laser scanning
      microscopy is a suitable approach to visualize the transport pathways of high
      molecular weight hydrophilic compounds across nasal epithelium, and to study the
      effects of absorption enhancers on drug transport and cell morphology.

PMID- 9165534
TI  - Inhibition of growth of Dictyostelium discoideum amoebae by bisphosphonate drugs
      is dependent on cellular uptake.
AB  - PURPOSE: The aim of the study was to determine whether bisphosphonates are
      internalised by Dictyostelium amoebae and whether cellular uptake is required for
      their growth-inhibitory effects. Bisphosphonates inhibit growth of amoebae of the
      slime mould Dictyostelium discoideum, by mechanisms that appear to be similar to
      those that cause inhibition of osteoclastic bone resorption. METHODS: Cell-free
      extracts prepared from amoebae that had been incubated with bisphosphonates were
      analysed by 31P-n.m.r, spectroscopy or ion-exchange f.p.l.c., to identify the
      presence of bisphosphonates or bisphosphonate metabolites respectively. The
      growth-inhibitory effect of bisphosphonates towards Dictyostelium amoebae was
      also examined under conditions in which pinocytosis was inhibited. RESULTS: All
      of the bisphosphonates studied were internalised by Dictyostelium amoebae,
      probably by fluid-phase pinocytosis, and could be detected in cell-free extracts.
      Amoebae that were prevented from internalising bisphosphonates by pinocytosis
      were markedly resistant to the growth-inhibitory effects of these compounds. In
      addition, bisphosphonates encapsulated within liposomes were more potent growth
      inhibitors of Dictyostelium owing to enhanced intracellular delivery of
      bisphosphonates. CONCLUSIONS: All bisphosphonates inhibit Dictyostelium growth by
      intracellular mechanisms following internalisation of bisphosphonates by fluid
      phase pinocytosis. It is therefore likely that bisphosphonates also affect
      osteoclasts by interacting with intracellular, rather than extracellular,
      processes.

PMID- 9165536
TI  - Macromolecules as novel transdermal transport enhancers for skin electroporation.
AB  - PURPOSE: Macromolecules were investigated as chemical enhancers of transdermal
      transport by skin electroporation. Although unable to enhance passive or
      iontophoretic transport, macromolecules are proposed to enhance electroporation
      assisted delivery by stabilizing the increased permeability caused by high
      voltage pulses. METHODS: To test this hypothesis, we examined the timescale of
      transport, the influence of electrical protocol and the influence of
      macromolecule size, structure, and charge on enhancement of transdermal mannitol
      transport in vitro by heparin, dextran-sulfate, neutral dextran, and poly-lysine.
      RESULTS: Skin electroporation increased transdermal mannitol delivery by
      approximately two orders of magnitude. The addition of macromolecules further
      increased transport up to five-fold, in support of the proposed hypothesis.
      Macromolecules present during pulsing enhanced mannitol transport after pulsing
      for hours, apparently by a macromolecule-skin interaction. No enhancement was
      observed during passive diffusion or low-voltage iontophoresis, suggesting that
      macromolecules interact specifically with transport pathways created at high
      voltage. Although all macromolecules studied enhanced transport, those with
      greater charge and size were more effective. CONCLUSIONS: This study demonstrates
      that macromolecules can be used as transdermal transport enhancers uniquely
      suited to skin electroporation.

PMID- 9165537
TI  - Restricted intestinal absorption of some beta-lactam antibiotics by an energy
      dependent efflux system in rat intestine.
AB  - PURPOSE: The purpose of this study was to examine factors limiting the intestinal
      absorption of orally inactive beta-lactam antibiotics. METHODS: Permeation
      behaviors of various beta-lactam antibiotics across rat intestinal segments were
      evaluated in vitro using diffusion cells. RESULTS: Poorly absorbed beta-lactam
      antibiotics, like cephaloridine and cefoperazone, commonly exhibit greater
      serosal-to-mucosal permeation than mucosal-to-serosal permeation, while
      cephalexin permeation was greater in the mucosal-to-serosal direction. In the
      absence of D-glucose, secretory-oriented permeation of cephaloridine and
      cefoperazone disappeared. Addition of sodium azide into an experimental buffer
      including D-glucose significantly and selectively enhanced mucosal-to-serosal
      permeation of cephaloridine and cefoperazone. Although benzylpenicillin,
      ampicillin, and amoxicillin all showed secretory-oriented permeation, the
      tendency to permeation was greatest with benzylpenicillin and least with
      amoxicillin. Probenecid stimulated mucosal-to-serosal permeation of
      cephaloridine, but verapamil and p-aminohippuric acid had no significant effect
      on it. CONCLUSIONS: It has been suggested that mechanisms which induce secretory
      oriented permeation of orally inactive beta-lactam antibiotics are factors
      limiting intestinal absorption of such antibiotics. This energy-demanding efflux
      system was distinct from P-glycoprotein-mediated transport. A free alpha-amino
      group in the molecule is an important factor for reducing an affinity with the
      efflux system.

PMID- 9165538
TI  - Blood-to-brain transfer of various oxicams: effects of plasma binding on their
      brain delivery.
AB  - PURPOSE: The objective of this work was to assess the influence of binding to
      plasma proteins and to serum on the brain extraction of four antiinflammatory
      oxicams. METHODS: The brain extraction of isoxicam, tenoxicam, meloxicam and
      piroxicam was investigated in rats using the carotid injection technique. Blood
      protein binding parameters were determined by equilibrium dialysis using human
      serum, human serum albumin (HSA) and alpha-l-acid glycoprotein (AAG) solutions at
      various concentrations. RESULTS: All oxicams had low values of brain extraction,
      between 19% and 39% when dissolved in serum, i.e. under physiological conditions.
      Brain efflux rate constants calculated from the wash-out curves were the same in
      the absence or presence of serum. Brain efflux was inversely related to the
      polarity of the oxicams, such that the higher their H-bonding capacity, the lower
      their brain efflux. The free dialyzable drug fraction was inversely related to
      protein concentration. However, rat brain extraction was always higher than
      expected from in vitro measurements of the dialyzable fraction. CONCLUSIONS:
      Except for piroxicam whose brain extraction was partially decreased in the
      presence of proteins, the serum unbound and initially bound fractions of oxicams
      both seem available for transfer into the brain. Modest affinities for AAG rule
      out any related effect. More surprising is the apparent lack of effect on brain
      transfer of the high-affinity binding to HSA and serum. The enhanced brain uptake
      of meloxicam in the presence of AAG could be a result of interactions between
      this globular protein and the endothelial wall.

PMID- 9165539
TI  - Preparation of biodegradable, surface engineered PLGA nanospheres with enhanced
      lymphatic drainage and lymph node uptake.
AB  - PURPOSE: Nanospheres can be utilised for the targeting of drugs and diagnostic
      agents to the regional lymph nodes. The surface modification of model
      polystyrene, (PS), and poly(lactide-co-glycolide),(PLGA), nanospheres by
      poly(lactide)-poly(ethylene glycol), (PLA:PEG), copolymers has been assessed by
      in vitro characterisation and in vivo biodistribution studies following
      subcutaneous administration of the nanospheres to the rat. METHODS: Three PLA:PEG
      copolymers were investigated, with PEG chain lengths of 750, 2000 and 5000 Da.
      The PLA:PEG copolymers were either coated onto the surface of PS and PLGA
      nanospheres or used as a co-precipitate in the formation of PLGA-PLA:PEG
      nanospheres. Coating of the nanospheres was confirmed by an increase in their
      particle size and a corresponding decrease in the surface potential. The kinetics
      of injection site drainage and lymph node retention was determined over a 24 hour
      time course for naked, coated and co-precipitated nanosphere systems. RESULTS:
      Dependent on the surface characteristics, the distribution of the nanospheres can
      be significantly modified and the lymph node localisation dramatically enhanced
      by coating their surfaces with PLA:PEG copolymers or by producing co-precipitate
      nanospheres of PLGA and PLA:PEG. CONCLUSIONS: A fully biodegradable nanosphere
      system has been developed with excellent lymph node targeting characteristics.

PMID- 9165540
TI  - cDNA cloning of the mouse bilirubin/phenol family of UDP-glucuronosyltransferase
      (mUGTbr2-like).

PMID- 9165541
TI  - Jejunal permeability: a comparison between the ussing chamber technique and the
      single-pass perfusion in humans.

PMID- 9165542
TI  - Effect of a chemical delivery system for dexamethasone (Dex-CDS) on peritumoral
      edema in an experimental brain tumor model.

PMID- 9165543
TI  - Isolation and characterization of major phase I and II metabolites of ibuprofen.

PMID- 9165544
TI  - The enhancer effect of several phenyl alcohols on percutaneous penetration of 5
      fluorouracil.

PMID- 9165545
TI  - 4-Aminopyridine improves pulmonary function in quadriplegic humans with
      longstanding spinal cord injury.
AB  - STUDY OBJECTIVE: To test the hypothesis that 4-aminopyridine (4-AP) might cause
      clinically evident improvement in pulmonary function in humans with chronic
      spinal cord injury (chronic SCI). DESIGN: Balanced, open-label study with
      subjects consecutively enrolled. SETTING: Spinal Cord Injury Service, university
      affiliated tertiary level care Department of Veterans Affairs Medical Center.
      PATIENTS: Seventeen healthy men and women suffering from traumatic SCI (11
      quadriplegic, 6 paraplegic patients) for more than 1 year. INTERVENTIONS: Each
      subject was given a single dose of 4-AP 10 mg orally in an immediate-release
      formulation. MEASUREMENTS AND MAIN RESULTS: Significant increases in mean values
      of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC),
      maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) that
      persisted for at least 12 hours were demonstrated in quadriplegic patients
      beginning 6 hours after 4-AP administration. Tests of pulmonary function that
      demonstrated statistically significant increases at any time were also
      numerically, if not statistically, increased at 24 hours compared with
      pretreatment values obtained in 4-AP-naive subjects. CONCLUSIONS: The
      administration of a single dose of an immediate-release formulation of 4-AP to
      humans with longstanding, traumatic quadriplegia is associated with sustained,
      clinically meaningful, and statistically significant improvements in pulmonary
      function. We suggest that the administration of 4-AP may have a salutary effect
      in patients suffering from SCI and appears to be associated with potentially
      clinically significant reductions in the pathophysiologic pulmonary sequelae of
      SCI.

PMID- 9165546
TI  - Pharmacokinetics and safety of concentration-controlled oral zidovudine therapy.
AB  - STUDY OBJECTIVE: To evaluate the pharmacokinetics, safety, and feasibility of
      concentration-controlled oral zidovudine therapy. DESIGN: Randomized, crossover,
      open-label study. SETTING: University-affiliated general clinical research
      center. PATIENTS: Eight individuals infected with the human immunodeficiency
      virus with CD4+ lymphocyte counts of 100 cells/microliter or greater.
      INTERVENTION: During the 24-week study, patients received oral zidovudine
      regimens that consisted of a standard fixed dose of 500 mg/day and a
      concentration-controlled regimen designed to maintain a steady-state plasma
      concentration (Css) of 0.187 +/- 0.04 mg/L (0.7 +/- 0.14 microM). MEASUREMENTS
      AND MAIN RESULTS: The mean Css during standard therapy was 0.170 +/- 0.024 mg/L
      versus 0.205 +/- 0.021 mg/L with the concentration-controlled regimen (p =
      0.025). Respective mean changes in hemoglobin were -0.02 g/dl (range -0.9-0.9
      g/dl) and -0.30 g/dl (range -1.5-0.4 g/dl, p = 0.67). The absolute neutrophil
      count decreased 0.90 x 10(9)/L during standard therapy and increased 0.40 x
      10(9)/L during concentration-controlled therapy (p = 0.07). The regimens did not
      differ in toxicity. CONCLUSION: Concentration-controlled oral antiretroviral
      therapy with zidovudine is feasible and safe, and provides pharmacologic data to
      determine the regimen's virologic and immunologic benefits.

PMID- 9165547
TI  - Pharmacometric analysis of the effect of furosemide on suramin pharmacokinetics.
AB  - STUDY OBJECTIVE: To characterize the effects of furosemide on the
      pharmacokinetics of suramin, a renally eliminated investigational antineoplastic
      agent. DESIGN: Retrospective population pharmacokinetic analysis. SETTING:
      Government biomedical research facility. PATIENTS: Twenty-six men with hormone
      refractory prostate cancer and one with adrenocortical carcinoma. INTERVENTIONS:
      Patients received suramin by continuous or intermittent infusion with and without
      concomitant furosemide. MEASUREMENTS AND MAIN RESULTS: Optimum suramin regimens
      were achieved by adaptive feedback control, and pharmacokinetic data were
      collected both in the presence and absence of furosemide. Suramin concentrations
      were determined by high-performance liquid chromatography (coefficient of
      variation < 8%). Suramin concentrations were fit to a three-compartment linear
      model with six coefficients and two rate inputs, which allowed furosemide to
      affect suramin pharmacokinetics. Individual and population parameter estimates
      were determined using the iterative two-stage approach. Concomitant furosemide
      was associated with a median decrease in total body clearance of suramin by 36%
      (range 0-63%, p < 0.0001). No other parameter was significantly altered, and
      there was no trend for change in any pharmacokinetic value with time. Suramin
      plasma concentrations were simulated with and without prolonged furosemide
      therapy in 26 patients for 12 weeks. The average suramin concentration increased
      by greater than 33% in 12 patients; 2 patients had a greater than 67% increase in
      this extreme case model. CONCLUSION: Coadministration of furosemide with suramin
      can cause an increase in suramin concentrations; however, due to suramin's long
      half-life, its rate of accumulation is very slow. Nonetheless, in individuals
      receiving suramin by nonadaptive control, appropriate precautions should be taken
      when prolonged furosemide therapy is begun.

PMID- 9165548
TI  - Effects of spontaneous gastric hypoacidity on the pharmacokinetics of zidovudine
      and didanosine.
AB  - STUDY OBJECTIVE: To determine the effect of spontaneous gastric hypoacidity on
      the pharmacokinetics of zidovudine and didanosine in subjects infected with the
      human immunodeficiency virus (HIV). DESIGN: Controlled, open-label, single-dose,
      pharmacokinetic study. SUBJECTS: Thirty-two asymptomatic HIV-infected subjects.
      INTERVENTIONS: Gastric pH studies were conducted in all 32 subjects, and 20 of
      these subjects (8 women, 12 men) were enrolled into the pharmacokinetic study.
      They were stratified into two groups according to fasting gastric pH: those
      without and with gastric hypoacidity (minimum gastric pH < 3 and > or = 3,
      respectively). Gastric pH was measured using the Heidelberg pH monitoring system
      in all subjects before and during pharmacokinetic analysis of zidovudine 100 mg
      or didanosine 200 mg (given as two 100-mg tablets dissolved in 6 oz water).
      Plasma samples were collected over 8 hours after dosing. MEASUREMENTS AND MAIN
      RESULTS: Six (20%) of 30 subjects had a minimum gastric pH of 3 or above on at
      least two occasions, and the remaining 2 had variable gastric pH. Although
      gastric pH was unchanged during the administration of zidovudine, it increased to
      greater than 9 in 11 of 12 subjects with didanosine, regardless of baseline
      value. For both drugs, there were no statistically significant differences in
      peak plasma concentration (Cmax), time to reach peak plasma concentration (Tmax),
      elimination rate constant (ke), and area under the plasma concentration-time
      curve from time zero to infinity (AUC0-infinity) between subjects with and
      without gastric hypoacidity despite sufficient statistical power to detect a 56%
      difference in clearance for either drug (alpha 0.05, beta 0.1). CONCLUSION:
      Gastric hypoacidity occurs in approximately 20% of HIV-infected patients and does
      not appear to influence zidovudine or didanosine pharmacokinetics.

PMID- 9165549
TI  - Evaluation of an open-loop, computer-based infusion system designed to achieve a
      series of constant, targeted plasma procainamide concentrations in patients
      undergoing electrophysiologic testing.
AB  - STUDY OBJECTIVE: To evaluate the performance of a computer-based procainamide
      infusion system in patients undergoing electrophysiologic testing. DESIGN:
      Prospective case series. SETTING: Electrophysiology laboratory in a university
      hospital. PATIENTS: Thirty-four patients with inducible sustained ventricular
      tachycardia. INTERVENTIONS: Intravenous infusion of procainamide to achieve and
      maintain targeted plasma concentrations. MEASUREMENTS AND MAIN RESULTS: System
      performance was assessed by comparing targeted and observed plasma
      concentrations. The population median absolute performance error (size of typical
      miss) was 12.6% (95% CI 11.2-14.1%). The population median performance error
      (system bias) was not significantly different from zero. A small but
      statistically significant improvement in performance over time was observed
      (population absolute performance error divergence -0.125%/min). Population wobble
      (overall system stability) was 7.6% (95% CI 6.8-8.3%). Population-based estimates
      of central compartment volume and volume of distribution at steady state were
      significantly higher and lower, respectively, than estimates used by the infusion
      system. CONCLUSION: The computer-based infusion system is capable of achieving
      and maintaining a series of targeted procainamide concentrations in patients
      undergoing electrophysiologic testing.

PMID- 9165550
TI  - Time-dependent disposition of tacrolimus and its effect on endothelin-1 in liver
      allograft recipients.
AB  - STUDY OBJECTIVE: To characterize a time-dependent disposition of oral tacrolimus
      and its relationship with plasma endothelin-1 concentrations. DESIGN: Randomized,
      crossover study. SETTING: Clinical research center of a university-affiliated
      hospital. PATIENTS: Twelve stable liver transplant recipients. INTERVENTIONS: In
      the steady state, 23 blood samples were taken from each patient before and after
      tacrolimus administration over 24 hours. MEASUREMENTS AND MAIN RESULTS: Whole
      blood samples for tacrolimus and plasma endothelin-1 were analyzed by enzyme
      immunoassay. The relationship of their concentrations and their pharmacokinetic
      parameters between morning and evening doses were compared. The area under the
      curve (AUC) of tacrolimus in the morning dose was significantly larger than that
      in the evening dose (219 +/- 54 ng.hr/ml and 188 +/- 57 ng.hr/ml, respectively, p
      = 0.004). The mean time to peak concentration (Tmax) was significantly shorter
      for the morning dose than for the evening dose (1.6 +/- 0.7 hrs and 3.5 +/- 2.9
      hrs, respectively, p = 0.01). The mean peak concentration (Cmax) was
      significantly higher in the morning dose than in the evening dose (32.2 +/- 9.1
      ng/ml and 21.6 +/- 8.3 ng/ml, respectively, p = 0.008). However, the mean through
      concentration (Cmin) was not significantly different between doses. Endothelin-1
      concentrations followed the same pattern as tacrolimus, with AUC and Cmax for the
      morning significantly higher than those for the evening dose of tacrolimus (AUC
      13.8 +/- 3.7 pg.hr/ml, morning, and 11.0 +/- 3.5 pg.hr/ml, evening, p = 0.005;
      Cmax 2.4 +/- 1.1 pg/ml morning, and 1.5 +/- 0.6 pg/ml evening, p = 0.02).
      Tacrolimus levels did not correlate with endothelin-1 levels (r2 = 0.06, p =
      0.001). CONCLUSIONS: Tacrolimus disposition in liver transplant patients is
      determined by time of administration. Plasma endothelin-1 concentrations follow
      the same pattern as blood tacrolimus concentrations.

PMID- 9165551
TI  - The use of microdialysis in pharmacokinetics and pharmacodynamics.
AB  - Microdialysis is a new in vivo sampling technology applied to the study of
      pharmacokinetics and drug metabolism in the blood and soft tissues of living
      systems. A small-diameter probe containing a dialysis membrane is implanted into
      tissue and perfused with a suitable fluid. Low-molecular-weight substances
      passively diffuse through the semipermeable membrane along a concentration
      gradient, resulting in the collection of purified dialysate samples. The
      advantage of this approach over blood sampling and dissection of tissues is the
      ability to sample blood and extracellular fluid with minimal tissue damage or
      alteration of fluid balance. Sampling several tissues simultaneously and
      continuously in animal models allows data to be obtained that more directly
      reflect interactions of drugs at their sites of activity and detoxification.
      Techniques such as this will have a tremendous impact on preclinical and clinical
      pharmacologic research.

PMID- 9165552
TI  - Disturbances of taste and smell induced by drugs.
AB  - We reviewed the current literature (1980-1990, 1991-1996) concerning drugs
      associated with anosmia, hyposmia, dysgeusia, parageusia, and ageusia, and the
      impact of these adverse effects. Case reports of patients with sudden and delayed
      onset of one of these disorders with evidence for implication of a drug were
      included. Disturbances of taste and smell among the elderly and chronically ill,
      including those with thermal injury, decreases interest in eating and secondarily
      impairs healing of wounds. Mechanisms involved with these sensory disturbances
      include deposition of silver sulfate in nerves after use of topical agents
      containing silver, altered influx of calcium and other ions, chelation or
      depletion of tissue-bound zinc, disturbed bradykinin catabolism and second
      messenger synthesis, catabolism, and altered prostaglandin systems. Other
      mechanisms, particularly prolonged chemosensory disorders after early drug
      discontinuation, remain unknown.

PMID- 9165553
TI  - Clinical issues associated with urine testing of substances of abuse.
AB  - Several factors may affect the validity and outcome of urine testing for abused
      drugs such as amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine,
      ethanol, opiates, and phencyclidine. Urine is used for large-scale testing
      because acquisition of the sample is noninvasive and because most abused drugs
      can be detected in urine for a reasonable duration after ingestion. Urine testing
      for drugs of abuse is a two-step process. In the first step, screening assays are
      used to identify presumably positive specimens. Common screening tests are
      radioimmunoassays, enzyme immunoassays, fluorescence polarization immunoassay,
      and thin layer chromatography. Since they may be subject to cross-reactivity,
      once a possible positive sample has been identified by a preliminary test, a
      second more specific methodology, gas chromatography with mass spectrometry, is
      done to confirm the results. Knowledge of the pharmacology and pharmacokinetics
      of abused drugs affects selection and interpretation of test results.

PMID- 9165554
TI  - Venlafaxine and nefazodone, two pharmacologically distinct antidepressants.
AB  - Venlafaxine, a phenylethylamine, and nefazodone, a phenylpiperazine compound, are
      the newest antidepressants to receive approval of the Food and Drug
      Administration and to be marketed in the United States. Both strongly inhibit
      serotonin (5-HT) reuptake; venlafaxine also inhibits norepinephrine reuptake, and
      nefazodone also exhibits 5-HT2-receptor antagonism. Venlafaxine inhibits the
      cytochrome P-450 2D6 isozyme to a lesser extent than the selective serotonin
      reuptake inhibitors (SSRIs) and is 27% protein bound. Structurally, the drugs are
      unrelated to SSRIs and have some clinically important differences in side effect
      profiles. Nausea, headache, somnolence, and dry mouth are the most frequently
      reported side effects with both. Sustained hypertension was reported by a limited
      number of venlafaxine-treated patients.

PMID- 9165555
TI  - Conduction disturbances associated with administration of butyrophenone
      antipsychotics in the critically ill: a review of the literature.
AB  - Droperidol and haloperidol have demonstrated efficacy and safety in the treatment
      of acute delirium in critically ill patients. We conducted MEDLINE and manual
      searches of literature published from 1966-1996 to identify articles describing
      conduction disturbances associated with the drugs. The objectives were to
      describe the proposed mechanisms of acquired long QTc interval syndrome and
      torsades de pointes, and to recommend how critically ill patients receiving these
      agents should be monitored. We found 11 published reports of conduction
      disturbances associated with intravenous administration of droperidol or
      haloperidol. The majority of cases occurred in critically ill patients prescribed
      more than 50 mg/24 hours of either agent. Of the 18 patients described, 13 (72%)
      had a history of cardiovascular disease. Based on the small number of available
      case reports, it seems reasonable to suggest that the incidence of adverse
      cardiovascular effects due to droperidol and haloperidol is small. The mechanism
      of butyrophenone-induced QTc interval prolongation is not known, but is presumed
      to involve abnormal ventricular repolarization and the development of early after
      depolarizations. Before initiating therapy with droperidol or haloperidol in
      critically ill patients, a baseline QTc interval and serum magnesium and
      potassium concentrations should be measured. If the baseline QTc interval is 440
      msec or longer, and they are receiving other drugs that may prolong the QTc
      interval or they have electrolyte disturbances, a butyrophenone antipsychotic
      should be prescribed with caution. All critically ill patients receiving
      droperidol or haloperidol should undergo electrocardiogram monitoring and QTc
      interval measurement; special attention should be given to those receiving doses
      greater than 50 mg/24 hours, as these patients appear to be at greatest risk for
      development of conduction disturbances. Based on the currently available
      literature, in any critically ill patient receiving droperidol or haloperidol
      therapy whose QTc interval lengthens by 25% or more over baseline, therapy should
      be discontinued or the dosage reduced.

PMID- 9165556
TI  - The fluconazole era: management of hematogenously disseminated candidiasis in the
      nonneutropenic patient.
AB  - Hematogenously disseminated candidiasis arising from nosocomial fungal infection
      is a life-threatening complication in critically ill, nonneutropenic patients.
      The overall nosocomial fungal infection rate in United States hospitals doubled
      from 1980-1990. Until recently, amphotericin B was the only agent available for
      the treatment of life-threatening candidal infections, but its use is plagued by
      toxicities including nephrotoxicity and infusion-related reactions such as rigors
      and hypotension. The availability of fluconazole, which is regarded as much less
      toxic than amphotericin B, prompted a surge in research to determine if it is as
      efficacious in the management of candidemia and hematogenously disseminated
      candidiasis. Complicating the interpretation of studies is the broad range of
      infection severity, from candidemia that may be transient and self-limiting to
      life-threatening hematogenously disseminated candidiasis. Clinical trials
      comparing fluconazole and amphotericin B demonstrate the efficacy of fluconazole
      for catheter-associated candidemia in critically ill patients when the likely
      pathogen is Candida albicans. Amphotericin B should remain the first-line agent
      for the management of candidemia and hematogenously disseminated candidiasis in
      all other patients.

PMID- 9165557
TI  - Aminoglycoside adaptive resistance.
AB  - Aminoglycoside adaptive resistance is defined as reduced antimicrobial killing in
      originally susceptible bacterial populations after initial incubation with
      aminoglycoside. It is observed in vitro and in vivo, most commonly with
      Pseudomonas aeruginosa. It appears to correlate with a marked reduction in
      intracellular aminoglycoside accumulation, although its specific mechanism and
      the cellular structures responsible remain unknown in P. aeruginosa. Recent work
      suggests that adaptive resistance develops coincident with cytoplasmic membranes
      protein changes and regulated expression of genes in the anaerobic respiratory
      pathway of the organism. It is clinically most relevant in immunocompromised
      patients and in those with serious infections, especially infections due to gram
      negative rods. Treatment of these patients by targeting high peak
      concentration:minimum inhibitory concentration ratios with once-daily dosing may
      result in the best outcome. A major unresolved issue concerns the effect of
      combination therapy on the development of aminoglycoside adaptive resistance.

PMID- 9165558
TI  - Octreotide and potassium homeostasis.
AB  - Somatostatin infusion causes hyperkalemia in healthy subjects and in some animal
      models. The purpose of this investigation was to determine what effect octreotide
      has on potassium homeostasis during serious illness and if there is a dose
      response relationship. Sixty-six male Sprague-Dawley rats (185-225 g) were
      randomized to receive parenteral nutrition (PN) only, PN plus continuous infusion
      of Escherichia coli lipopolysaccharide (LPS), or PN plus LPS plus octreotide 10,
      100, or 1000 micrograms/kg/day for 48 hours. Before randomization all animals
      received isocaloric, isonitrogenous, isokalemic PN. A 24-hour urine was collected
      and a blood sample was taken at the end of the study immediately before
      euthanization. Data were analyzed by ANOVA and Duncan's multiple range test.
      Nonhemolyzed serum samples from 50 rats were available for study. Serum potassium
      concentrations were in the normal range for rats and did not differ significantly
      among the groups: 5.97 +/- 0.86, 5.96 +/- 1.58, 5.78 +/- 1.48, 5.79 +/- 1.67,
      5.35 +/- 0.78 mEq/L, respectively. No differences among groups were found for
      fractional excretion of potassium or serum creatinine concentration. Octreotide
      administration in escalating dosages does not cause hyperkalemia in endotoxemic
      rats given intravenous potassium at a constant rate by PN.

PMID- 9165559
TI  - Anticonvulsants and congenital malformations.
AB  - Earlier studies indicated that the prevalence of congenital anomalies is greater
      in infants of epileptic mothers treated with anticonvulsants than in infants of
      mothers without epilepsy. We carried out a study of women in the General Practice
      Research Database who delivered liveborn infants between January 1988 and March
      1993 and who were exposed to an anticonvulsant drug during the first trimester of
      pregnancy, and women with epilepsy not treated with anticonvulsants during
      pregnancy. We matched two nonexposed women without epilepsy to each exposed woman
      for age at delivery, date of baby's birth, and general practice. Two hundred
      ninety-seven women treated for epilepsy had 10 liveborn infants with major
      anomalies (3.4%) compared with 6 of the 594 nonexposed women (1.0%, RR = 3.3, 95%
      CI 1.2-9.2). We conclude that the infants of women with epilepsy who are treated
      with an anticonvulsant during the first trimester of pregnancy have an increased
      risk of major congenital anomalies.

PMID- 9165560
TI  - Salary survey of ambulatory care clinical pharmacists.
AB  - To determine salary and selected fringe benefits of members of the Ambulatory
      Care Practice and Research Network of the American College of Clinical Pharmacy,
      we developed a self-administered questionnaire that surveyed demographic
      information, schooling and training, academic appointments, yearly salary (as of
      February 1, 1995), source of salary, outside income, annual raise, vacation time,
      financial support for continuing education, and board certification. Ninety-nine
      surveys were returned (return rate 46%). Respondents were mostly women (58%),
      their average age was 34 years (range 25-51 yrs), and they had a median of 5
      years in the work force. Most respondents (67%) had residency training, whereas
      only 21% had fellowship experience. Board certification was reported by 46%. The
      median salary was $53,500 (average $55,861, range $35-90 k), with progression for
      academic rank. The last salary increase averaged 3.7%. Most (93%) respondents
      received an average of $1509 for travel. The survey represents a young work
      force. The salaries vary but show progression for accomplishment.

PMID- 9165561
TI  - Early switch from intravenous to oral antibiotics in hospitalized patients with
      infections: a 6-month prospective study.
AB  - We assessed what percentage of hospitalized patients treated with intravenous
      antibiotics would be candidates for early switch to oral therapy, and evaluated
      the clinical outcomes of patients after the switch. All hospitalized patients in
      whom an intravenous antibiotic was prescribed for treatment of an infection were
      prospectively screened to identify candidates for switch in therapy. Of the 655
      patients treated with intravenous antibiotics, 300 (46%) were candidates for a
      switch, and the change was implemented in 262 (40%). Of the 171 evaluable
      patients, the switch was associated with clinical cure in 167 (98%) and failure
      in 4 (2%). In hospitalized patients with infections, the duration of intravenous
      antibiotic therapy can be minimized with early switch to oral therapy. This
      practice is associated with good patient outcome.

PMID- 9165562
TI  - Effect of pharmaceutical care on optimum colestipol treatment in elderly
      hypercholesterolemic veterans.
AB  - We conducted a prospective trial to determine whether a formal, integrated
      pharmaceutical care plan can enhance patient acceptance and compliance with
      colestipol therapy and improve outcomes. Forty patients with hypercholesterolemia
      were equally divided and assigned to either a usual care or pharmaceutical care
      group. In the pharmaceutical care group compared with the usual care group, after
      52 weeks, colestipol therapy resulted in a greater reduction in total cholesterol
      (12.5% vs 7.3%), low-density lipoprotein cholesterol (LDL-C; 16% vs 9.4%), and
      LDL-C:high-density lipoprotein cholesterol (HDL-C) ratio (24.4% vs 12.2%, p <
      0.05). The percentage of patients who achieved their LDL-C goal at week 52 was
      much greater in the pharmaceutical care group (29.4%) than in the usual care
      group (5.0%, p < 0.05). Co-management by a physician and a pharmacist of
      hypercholesterolemic veterans treated with colestipol can enhance patient
      acceptance of the drug, LDL-C reduction, and achievement of therapeutic goals.

PMID- 9165563
TI  - Is the volume of distribution of digoxin reduced in patients with renal
      dysfunction? Determining digoxin pharmacokinetics by fluorescence polarization
      immunoassay.
AB  - STUDY OBJECTIVE: To determine digoxin pharmacokinetics in subjects with different
      degrees of renal function using fluorescence polarization immunoassay (FPIA),
      which is associated with less interference from digoxin-like immunoreactive
      substances (DLIS) than radioimmunoassay. SETTING: University hospital clinical
      research center. PARTICIPANTS: Eighteen subjects (mean age 44 yrs) with different
      degrees of renal function: group 1, creatinine clearance (Clcr) below 10
      ml/minute; group 2, Clcr 10-50 ml/minute; and group 3, Clcr greater than 50
      ml/minute (6 patients in each group). INTERVENTION: Over 5-7 days, 15 serum
      samples were collected after a single intravenous dose of digoxin 7 or 10
      micrograms/kg actual body weight (WT) for serum concentration measurements by
      FPIA. Two-compartment pharmacokinetic parameters (zero-time intercept of the
      concentration-time curve of the initial distribution phase [A], zero-time
      intercept of the concentration-time curve of the terminal elimination phase [B],
      initial distribution phase constant [alpha], terminal elimination rate constant
      [beta], volume of distribution in the central compartment [Vc] and at steady
      state [Vss], total body clearance [Cl], mean residence time [MRT], area under the
      concentration-time curve [AUC]) were determined using a nonlinear least squares
      regression program. MEASUREMENTS AND MAIN RESULTS: No significant differences
      were found among groups for A, B, alpha, beta, beta-half-life Vc/WT, MRT, AUC,
      and Cl/WT. Significant differences were observed in Vss/WT (4.8 +/- 1.0, 6.6 +/-
      0.5, 6.4 +/- 0.7 L/kg) between group 1 versus group 2 and group 1 versus group 3
      (p < 0.01). Measured Clcr was correlated with Cl (r2 = 0.40, p < 0.01), Cl/WT (r2
      = 0.29, p < 0.05), Vss (r2 = 0.35, p = 0.01), and Vss/WT (r2 = 0.24, p < 0.05).
      CONCLUSION: This study confirmed that Vss is smaller in patients with chronic
      renal failure (Clcr < 10 ml/min) than those without chronic renal failure.
      Therefore, previous recommendations that lower digoxin loading doses should be
      administered in patients with renal failure are applicable to digoxin serum
      concentration monitoring using FPIA.

PMID- 9165564
TI  - Pharmacokinetics of mycophenolate mofetil and intravenous ganciclovir alone and
      in combination in renal transplant recipients.
AB  - STUDY OBJECTIVES: To evaluate the pharmacokinetics of mycophenolic acid and its
      glucuronide metabolite alone and in the presence of ganciclovir, and to determine
      the pharmacokinetics of ganciclovir alone and in combination with mycophenolate
      mofetil. DESIGN: Randomized, open-label, three-way crossover study. PATIENTS:
      Twelve kidney transplant recipients. INTERVENTIONS: Mycophenolate mofetil 1500 mg
      orally and ganciclovir 5 mg/kg intravenously were each given alone and in
      combination with at least a 1-week washout period between treatment arms.
      MEASUREMENTS AND MAIN RESULTS: Blood samples were obtained to measure
      mycophenolic acid and ganciclovir by high-performance liquid chromatography. Mean
      (+/-SD) oral plasma clearance for mycophenolic acid alone and with ganciclovir
      was 3.11 +/- 0.72 and 3.19 +/- 0.72 ml/min/kg (p = 0.64). The overall disposition
      of the major metabolite, MPA-glucuronide, was unchanged, with approximately 70%
      of the administered dose eliminated as the glucuronide conjugate for both arms of
      the study. Mean genciclovir serum clearance was 1.80 +/- 0.58 ml/min/kg for
      ganciclovir and 1.70 +/- 0.55 ml/min/kg for ganciclovir plus mycophenolate
      mofetil (p = 0.11; 10 patients). Renal clearance of ganciclovir was decreased
      when the drugs were administered in combination, 1.43 +/- 0.54 (ganciclovir) and
      1.26 +/- 0.44 (both drugs) ml/min/kg (p = 0.02; 10 patients). CONCLUSION: The
      single-dose pharmacokinetics of mycophenolic acid and its glucuronide metabolite
      were unchanged by the addition of ganciclovir. Total serum clearance of
      ganciclovir was unchanged by the addition of mycophenolate mofetil, however,
      renal clearance was slightly decreased.

PMID- 9165566
TI  - Recurrent Clostridium difficile diarrhea associated with mitoxantrone and
      etoposide: a case report and review.
AB  - Clostridium difficile colitis most commonly occurs in association with antibiotic
      administration and infrequently with antineoplastic agents. Our patient
      experienced recurrent C. difficile diarrhea associated with mitoxantrone and
      etoposide. He received antibiotics during the 6 months, but each episode of
      diarrhea was preceded by at least a 6-week antibiotic-free period. In addition,
      antineoplastic therapy preceded each episode by 8 or 9 days. Clinicians should be
      aware that antineoplastic drugs may precipitate overgrowth of C. difficile in the
      bowel.

PMID- 9165565
TI  - Risperidone: effects of formulations on oral bioavailability.
AB  - The bioavailability of risperidone was evaluated in an open-label, randomized,
      two-way, crossover study comparing a 1-mg tablet with a 1-mg/ml oral solution.
      Both formulations were administered as a single 1-mg dose with a 10-day washout
      period between treatments. Of 26 healthy men who entered the study, 23 completed
      both treatment periods. Plasma concentrations of risperidone and the active
      moiety (risperidone plus its active metabolite, 9-hydroxyrisperidone) were
      determined by radioimmunoassays. For key pharmacokinetic values (Cmax, AUC), the
      90% CIs on the relative bioequivalence of risperidone, 9-hydroxyrisperidone, and
      the active moiety were contained within the equivalence range of 80-120% (80-125%
      for log-transformed data). The results demonstrate that the 1-mg/ml oral solution
      and the 1-mg tablet are bioequivalent.

PMID- 9165568
TI  - Neuroleptic malignant syndrome with risperidone.
AB  - Neuroleptic malignant syndrome is thought to be a result of dopamine D2 receptor
      blockade in the striatum of the basal ganglia. Risperidone, a benzisoxazole
      derivative antipsychotic, has high serotonin 5-HT2 receptor blockade and dose
      related D2 receptor blockade. The high ratio is believed to impart the low
      frequency of extrapyramidal symptoms with risperidone at low dosages. With this
      low frequency of extrapyramidal symptoms, it was thought the frequency of
      neuroleptic malignant syndrome might also be lowered. A 73-year-old woman
      developed neuroleptic malignant syndrome after monotherapy with risperidone. The
      syndrome reversed after discontinuing risperidone and starting treatment with
      dantrolene and bromocriptine. It appears that the protection from extrapyramidal
      side effects observed with risperidone does not ensure protection from
      neuroleptic malignant syndrome.

PMID- 9165567
TI  - Female sexual stimulation during antidepressant treatment.
AB  - Three women with several diagnoses, including depression and psychosis,
      personality disorder, attention deficit hyperactivity disorder, alcohol abuse,
      and physical disease, were treated with selective serotonin reuptake inhibitors
      (fluoxetine, paroxetine, fluvoxamine). One patient was prescribed paroxetine in
      addition to methylphenidate. While receiving these agents, two women experienced
      undesirable sexual arousal and the third had increased sexual desire, arousal,
      and hypersexuality.

PMID- 9165569
TI  - Prolonged quinidine half-life with associated toxicity in a patient with hepatic
      failure.
AB  - A markedly prolonged quinidine elimination half-life due to hepatic failure and
      resultant quinidine toxicity occurred in a 57-year-old man with a history of
      atrial fibrillation. A prolonged QT interval, development of torsades de pointes,
      and a serum quinidine concentration of 3.1 micrograms/ml contributed to a
      decision favoring permanent pacemaker implantation. The apparent quinidine half
      life ranged from 66-99 hours and was associated with QT prolongation and
      persistent U waves. On discontinuing quinidine, all signs associated with
      toxicity resolved as serum quinidine concentrations decreased, which resulted in
      reversal of the decision to implant a permanent pacemaker. This case reports an
      extremely long quinidine elimination half-life and reillustrates the importance
      of drug pharmacokinetics in patient care.

PMID- 9165570
TI  - QT prolongation and development of torsades de pointes with the concomitant
      administration of oral erythromycin base and quinidine.
AB  - Torsades de pointes is a polymorphic ventricular tachycardia characterized by
      marked QT prolongation on the electrocardiogram. It can be induced by both
      antiarrhythmic and nonantiarrhythmic drugs, such as quinidine and erythromycin.
      No extensive literature documents an interaction between quinidine and
      erythromycin when the agents are administered orally. A 95-year-old man received
      oral quinidine and erythromycin for the treatment of atrial fibrillation and
      community-acquired pneumonia. He developed torsades de pointes and subsequently
      cardiac arrest. Since erythromycin and quinidine are known to cause arrhythmias
      individually, caution and close monitoring are necessary when the drugs are
      administered concomitantly.

PMID- 9165572
TI  - Survival after high-dose intraperitoneal infusion of glycine solution in the
      mouse.
AB  - We used an animal model to study whether glycine prompts death after absorption
      of irrigating fluid by the extravascular route. Mice were divided into groups of
      10 and given an intraperitoneal infusion of 200, 225, 250, 275 or 300 ml/kg of
      glycine 1.1%, 1.5% or 2.2%. With all infused volumes, the chance of survival was
      better after infusion of glycine 1.1% and glycine 1.5% than after glycine 2.2%.
      The overall death rates were 10%, 16% and 46%, respectively. Logistic regression
      analysis showed that the outcome was significantly and independently affected by
      both the glycine concentration and the infused volume. We conclude that the
      glycine concentration of an irrigating fluid deposited in the peritoneal cavity
      is important to the chance of survival. The poorest chance is obtained with
      glycine 2.2%.

PMID- 9165571
TI  - Multisite mucous membrane bleeding due to a possible interaction between warfarin
      and 5-fluorouracil.
AB  - A 59-year-old man being treated for colon cancer experienced epistaxis,
      hematemesis, hematuria, and hematochezia. Laboratory evaluation revealed a
      greatly prolonged prothrombin time. It is possible that the bleeding was due to
      an interaction between 5-fluorouracil and warfarin. The former may inhibit the
      synthesis of cytochrome P-4502C9, leading to impaired metabolism of the latter.

PMID- 9165573
TI  - Surgical enucleation for renal cell carcinoma (RCC). Prognostic significance of
      tumour stage, grade and DNA ploidy.
AB  - This study reviews a total of 26 renal cell carcinoma (RCC) who underwent
      enucleation of the tumour with functionally and anatomically normal controlateral
      kidney and no evidence of systemic renal disease. At follow-up, after a mean of
      62 months the disease specific survival rate for this series was 88.5%. Survival
      rates according to the pathologic stage, grading, tumour diameter and ploidy are
      reported. Local recurrences were documented in 4 of the 26 RCC. All 4 RCC were
      more than 5 cm in diameter and recurred in the remaining parenchyma. After local
      recurrence, three tumours with aneuploid DNA content underwent radical
      nephrectomy, whereas 1 with diploid DNA content was submitted to a new
      enucleation of the recurrence. To date the diploid case is still alive 3 years
      after the original resection of the primary tumour whereas the other 3 patients
      died for metastatic disease. In our experience the ideal candidate for renal
      sparing surgery in the presence of a normal opposite kidney is an asymptomatic
      patient that incidentally is brought to our attention with a small size (less
      than 5 cm in diameter), low stage (T1-T2) tumour, well surrounded by a
      pseudocapsule. DNA content is a valuable prognostic factor in patients submitted
      to conservative surgery. Diploid tumours have been seen to have a better
      prognosis and in case of local recurrence they may be reconsidered for a new
      enucleation of the recurrence.

PMID- 9165574
TI  - Benign retroperitoneal neural sheath tumors in patients without von
      Recklinghausen's disease.
AB  - Benign retroperitoneal neural sheath tumors in patients without von
      Recklinghausen's disease are quite rare and usually presented as isolated case
      reports. There are two types of benign neural sheath neoplasms: schwannoma and
      neurofibroma. Confusion exists in the nomenclature of these tumors due to the
      disagreement upon their cell of origin. In a collective report from two
      institutions, three cases with benign retroperitoneal neural sheath tumors are
      presented, and the histological features, diagnostic and therapeutic options are
      discussed.

PMID- 9165575
TI  - In situ extracorporeal shock wave lithotripsy for acute renal colic due to
      obstructing ureteral stones.
AB  - The purpose of the present study was to evaluate in situ extracorporeal shock
      wave lithotripsy (ESWL) for the treatment of obstructing ureteral stones causing
      acute renal colic. In situ ESWL with an EDAP LT-02 piezo-electric lithotriptor
      was used in a prospective study to treat 67 patients with obstructing ureteral
      stones causing acute renal colic. Patients were treated without anesthesia on an
      out-patient basis or during a one-day hospital stay. The overall one month stone
      free rate was 94% (94% for proximal stones and 95% for distal stones). The
      overall success rate after a single ESWL session was 81%. Treatment was well
      tolerated in 90% (60/67) of patients. There was one case of non-obstructive
      pyelonephritis and one of ureteral edema. These rates compare well with published
      reports for delayed treatment in patients without renal colic. Immediate ESWL for
      cases of acute renal colic due to obstructing ureteral stones is an effective
      treatment strategy that warrants wider consideration.

PMID- 9165576
TI  - Effects of percutaneous nephrolithotomy and extracorporeal shock wave lithotripsy
      on renal function and prostaglandin excretion.
AB  - The aim of the study was to investigate the effects of percutaneous
      nephrolithotomy (PCN) and extracorporeal shock wave lithotripsy (ESWL) on renal
      function and urinary prostaglandin excretion. Twenty/ESWL patients and 20 PCN
      patients were studied pre-, 24 h and two weeks after treatment. Twenty-four hours
      after treatment PCN resulted in a fall in serum potassium, sodium and calcium.
      There was a small rise in urinary prostaglandin excretion. All results had
      returned to normal by two weeks. ESWL caused a rise in serum creatinine with a
      fall in calculated glomerular filtration rate (GFR). This was coupled with a fall
      in urinary excretion of sodium, potassium, and calcium. There was a rise in
      urinary prostaglandin excretion. Serum calcium and LDH levels also rose. All
      results had returned to normal by two weeks except urinary calcium excretion, and
      serum albumin had now fallen. ESWL had more effect on renal function in the acute
      phase of treatment than PCN.

PMID- 9165577
TI  - Primary signet ring cell carcinoma of the bladder: a report on 10 cases.
AB  - Primary signet ring cell cancer of the urinary bladder is a rare tumour with some
      70 cases reported to date. We report on ten additional cases with long-term
      follow-up. All 713 primary bladder tumours in western Sweden diagnosed during a 2
      year period were prospectively registered and followed and all the
      histopathological material reviewed. A clinical and histopathological review of
      816 bladder tumours from the files of the Oncology Clinic treated between 1962
      and 1989 was performed. An incidence of primary signet ring cell carcinoma of
      0.6% was found. Three out of five patients who were worked up as a result of an
      occasional episode of macroscopic haematuria were tumour-free 2, 5 and 14 years,
      respectively, after radical transurethral resection. Seven patients died of the
      disease after 5-26 (median 19) months. Our study and a review of the literature
      indicate that the majority of patients with primary signet ring cell carcinomas
      are diagnosed at an advanced stage and survival is poor. However, some patients
      with small tumours at diagnosis were tumour-free after transurethral resection.
      Radiotherapy was ineffective in most cases. Systemic chemotherapy is of no
      benefit.

PMID- 9165578
TI  - Morbidity after preoperative radiotherapy and cystectomy in patients with bladder
      cancer.
AB  - The therapy-related morbidity was evaluated in 121 patients with muscle-invasive
      or recurrent superficial bladder cancer treated with radiotherapy and cystectomy.
      In 103 patients cystectomy succeeded 39-52 Gray (Gy) preoperative irradiation and
      in 18 patients cystectomy was done as a salvage procedure after previous full
      dose radiotherapy. The overall frequency of complications was high; 71% of the
      patients treated with preoperative and 78% treated with full-dose radiotherapy
      had clinically relevant complications related to radiotherapy or surgery or both.
      The rate of intestinal complications was 39% for preoperative and 67% for full
      dose radiotherapy. The overall mortality rate in intestinal complications was
      3.3%. This study shows that the combination of radiotherapy and radical surgery
      in patients with bladder cancer is associated with a high rate of intestinal
      complications. The complications are significantly related to the irradiation
      dose and are long lasting and even life threatening.

PMID- 9165579
TI  - A questionnaire study of sexological problems following urinary diversion in the
      female patient.
AB  - A questionnaire study was conducted to evaluate the sexological problems after
      urinary diversion, using the continent Kock reservoir or the ileal conduit
      diversion. Thirty-seven female patients completed the questionnaire: 17 patients
      had a continent and 20 an ileal conduit diversion, with a median follow-up of 0.8
      year (range 0.5-4.4) and 4.6 years (range 2.8-12.0), respectively. Data from only
      33 patients were eligible for analysis, but no significant between-group
      differences were found. Coital frequency remained unchanged or increased among
      44% of patients with a continent reservoir and among 18% of ileal conduit
      patients (p = 0.11). Among those reporting other than unchanged/increased
      activity almost one-third gave physical problems or decreased desire as the
      reason, and 30% felt less sexually attractive, with cystectomized patients
      reporting a higher percentage than others. A higher frequency of dyspareunia
      among patients with a continent reservoir was an unexpected finding (p = 0.06),
      and merits further investigation in a larger sample. Here it may be due to the
      shorter follow-up of these patients. Thirty per cent of all patients would have
      like more sexological counselling.

PMID- 9165580
TI  - Transitional cell carcinoma express vitamin D receptors.
AB  - Recently, vitamin D analogues have shown antineoplastic effect in several
      diseases. Vitamin D analogues exert its effect by interacting with the vitamin D
      receptor (VDR). Studies of VDR in transitional cell carcinoma (TCC) have not been
      reported. The purpose of the present study was therefore to examine whether human
      bladder tumor cells express VDR. Tumor biopsies were obtained from 26 patients
      with TCC. Expression of VDR was examined by immunohistochemical experiments. All
      tumors expressed VDR. Biopsies from advanced disease contained more VDR positive
      cells than low stage disease (p < 0.05). Similarly, also tumor grade appeared to
      be related to the number of cells expressing the receptor. Normal urothlium also
      expressed VDR but only with low intensity. Our study shows that TCC cells possess
      the VDR receptor which may make them capable to respond to stimulation with
      vitamin D, but functional studies of vitamin D's effect on TCC cells in vitro are
      necessary before the efficacy of treatment with vitamin D analogues in TCC can be
      evaluated in patients.

PMID- 9165581
TI  - Treatment of high-grade, high-stage prostate cancer with estramustine phosphate
      or diethylstilbestrol. A double-blind study. The SPCG-1 Study Group. Scandinavian
      Prostate Cancer Group.
AB  - Between 1984 and 1989, 197 patients with T1-4, NX, M1, G2-3 or G3 prostate cancer
      were randomized to treatment with 560 mg estramustine phosphate (EMP, Estracyt,
      Emcyt) or 3 mg diethylstilbestrol (DES) per day in a double blind study with
      stratification on presence or absence of cancer pain at start. A total of 194
      patients were evaluated for efficacy of therapy. Time to progression (p = 0.054),
      to treatment failure (p = 0.036), cancer-specific survival (p = 0.068) as well as
      overall survival (p = 0.021) were longer in the DES group. There were more
      patients with prognostic parameters indicating bad prognosis in the EMP group.
      This trial was designed to study whether EMP had better effect than DES as the
      primary treatment of high-grade, disseminated prostate cancer. The results did
      not confirm this hypothesis. On the contrary, treatment with DES had relatively
      good effect on this very aggressive form of prostate cancer.

PMID- 9165582
TI  - Effect of transurethral microwave thermotherapy on serum concentrations of total
      and free prostate-specific antigen.
AB  - This study includes 15 men between 48 and 81 years of age with treatment
      requiring symptomatic benign prostatic hyperplasia (BPH). No patient with a
      urinary infection or prostate cancer was included. The serum concentrations of
      prostate-specific antigen (PSA), total as well as "free", i.e. noncomplex bound,
      were repeatedly determined before and up to 3 months after transurethral
      microwave thermotherapy (TUMT) of the prostate. After TUMT we found significant
      rises of the ratios of the serum total PSA concentration/prostate volume (up to
      55-fold, mean 13.1) and of the serum free PSA concentration/ prostate volume (up
      to 26-fold, mean 10.2). The highest values for the serum total PSA
      concentration/prostate volume ratio were found on the first day after TUMT.
      Maximal serum free PSA concentration/prostate volume ratio occurred 3-6 h after
      treatment. The serum concentration/prostate volume ratios for total and free PSA
      returned to normal within 3 months. The results indicate that PSA determinations
      might be used as effect indicators of TUMT.

PMID- 9165583
TI  - Varicocele testis evaluated by CT-scanning.
AB  - To evaluate and depict CT-scanning of the spermatic cord in seven men with
      varicocele testis, during quiet breathing and during Valsalva's manoeuvre. With
      the patients supine, two transverse scans were made during quiet breathing and
      two with the intra-abdominal pressure increased by a Valsalva manoeuvre. The
      transsectional area of the spermatic cord varied between 80 and 100 mm2 on the
      normal sides and between 100 and 200 mm2 on the affected sides. Raised intra
      abdominal pressure dilated the veins of the pampiniform plexus, increasing the
      trans-sectional area by 40-80% on the normal sides and by 100 to 200% on the
      affected sides. A spermatic cord area as measured at the root of the scrotum of
      more than 100 mm2 without raised intra-abdominal pressure, and more than 200 mm2
      with, signals a varicocele. CT-scanning with raised intra-abdominal pressure can
      be used as a safe and non-invasive method to detect a varicocele testis and to
      show its proximal extension into the inguinal canal. We would also recommend this
      investigation in patients with unexplained groin pain.

PMID- 9165584
TI  - Better response to s.c. erythropoietin in CAPD than HD patients.
AB  - The clinical efficacy of s.c. erythropoietin (EPO) injected subcutaneously once
      weekly was compared in patients (median age of 63 years) on peritoneal dialysis
      (PD, n = 19) and in haemodialysis (HD, n = 13). The blood haemoglobin prior to
      start of EPO was not significantly different between the groups. The mean (+/-
      SD) dose of EPO given to achieve a blood haemoglobin level of 100 g/l was not
      significantly different between the PD and the HD-responders (85 +/- 45 units/kg
      body weight and week, versus 112 +/- 33, respectively). Significantly more
      patients using PD than in HD achieved a haemoglobin level > or = 95 g/l (p =
      0.02). The HD group had significantly higher ferritin values. Serum iron and
      intact PTH were not different between the groups. In conclusion, s.c. EPO
      injections once, or occasionally twice, weekly increased blood haemoglobin levels
      in a greater proportion of patients on PD than in those on HD.

PMID- 9165585
TI  - Incidentally detected renal angiomyolipoma with tumour thrombus into the inferior
      vena cava.
AB  - A right-renal angiomyolipoma with tumour thrombus into the inferior vena cava was
      incidentally detected. This is the ninth published case of its type and the
      second incidental case. Presence of a thrombus does not imply invasive disease,
      but the tumour then is often bigger than 6 cm and radical surgery is mandatory.

PMID- 9165586
TI  - Successful conservative management of emphysematous pyelonephritis, bilateral or
      in a solitary kidney.
AB  - Emphysematous pyelonephritis, bilateral or in a solitary kidney, is a life
      threatening condition that requires prompt diagnosis and early intervention.
      Reported mortality is high, despite desperate surgical measures often ending in
      loss of renal unit, but medical management, possibly combined with percutaneous
      drainage, is sometimes successful. We report two cases of emphysematous
      pyelonephritis, one bilateral and one in a solitary kidney, with successful
      conservative management. Predisposing factors were insulin-dependent diabetes
      mellitus and micronodular cirrhosis secondary to chronic alcoholism. Prompt
      sonographic diagnosis determined the success of conservative management.
      Escherichia coli was identified as causal factor. In the bilateral case the
      clinical picture improved within 48 h after control of diabetes and broad
      spectrum antibiotic treatment. For the affected solitary kidney, percutaneous
      drainage and ureteric catheterization were required.

PMID- 9165588
TI  - The first case of periureteric hibernoma. Case report.
AB  - Hibernoma is a rare type of soft tissue neoplasm originating from brown fat
      tissue. The present case is the first periureteric hibernoma concentrically
      surrounding the ureter with a concomitant renal pelvis stone.

PMID- 9165587
TI  - Multiple but different urothelial tumours in one side of a urinary tract.
AB  - We present a combination of transitional cell carcinoma and a well differentiated
      squamous cell carcinoma in the right side of the urinary tract of a bilharzial
      patient. The right renal pelvis and the right ureter demonstrated transitional
      cell carcinoma, while the right lateral wall of the bladder showed squamous cell
      carcinoma.

PMID- 9165589
TI  - Iatrogenic external iliac artery disruption during open pelvic lymph node
      dissection: successful repair with hypogastric artery transposition.
AB  - We report the first case of a wide, iatrogenic, proximal disruption of the right
      external iliac artery, occurring during staging open lymph node dissection for
      prostate cancer, which was repaired by hypogastric artery transposition. The
      hypogastric artery was mobilized and rotated anteriorly, and sutured to the
      distal segment of the external iliac artery. This is a feasible, innovative and
      safe technique which permits, by a single anastomosis, the secure reconstruction
      of a vascular axis to the leg when other procedures are not accessible.

PMID- 9165590
TI  - Cisapride enhances detrusor contractility and improves micturition in a woman
      with lazy bladder.
AB  - A 32-year-old woman with lazy bladder was treated with cisapride (10 mg q.i.d.)
      for three weeks, obtaining a progressive improvement of the symptomatology and
      urodynamic parameters, and the return to pretreatment conditions after drug
      withdrawal. This case agrees with the evidence that cisapride potentiates the
      release of acetylcholine from postganglionic cholinergic nerves in the human
      isolated detrusor by activating 5-HT4 receptors, i.e. through the same mechanism
      responsible for its gastrointestinal prokinetic action. It is concluded that
      selective 5-HT4 agonists could be potentially useful to improve bladder emptying
      in micturition disorders associated with detrusor hypocontractility.

PMID- 9165591
TI  - Reiter syndrome following intracavitary BCG administration.
AB  - BCG vaccine was given intravesically to a patient with bladder tumour. After the
      fifth dose she developed bilateral conjunctivitis, painful swelling in her wrist,
      dysuria and arthritis in her left knee and right metacarpophalangial joints. The
      diagnosis was Reiter syndrome and is the second case in the literature.

PMID- 9165592
TI  - Chronic prostatic pain. A new treatment option with finasteride?
AB  - Chronic nonbacterial prostatitis and prostatodynia are difficult entities to
      treat. We have treated four patients successfully with finasteride Proscar, MSD.

PMID- 9165593
TI  - A case of growing teratoma syndrome.
AB  - Residual masses are a common finding after chemotherapy for metastases from
      nonseminomatous germ cell tumours of the testes. The prognosis of these patients
      with resected teratoma following successful cisplatin-based combination
      chemotherapy generally has been assumed to be good. Herein we reported an unusual
      teratoma case named "growing teratoma syndrome' by Logothetis et al. This patient
      was treated with multiple operations.

PMID- 9165594
TI  - Severe thrombosis after chemotherapy for metastatic choriocarcinoma of the testis
      maintaining complete remission for a long period.
AB  - We report the favourable outcome of a patient who suffered from severe arterial
      and venous thrombosis during chemotherapy for testicular pure choriocarcinoma. An
      increased paraneoplastic stimulus of HCG secondary to the marker surge phenomenon
      is suggested as responsible for transient hypercoagulability and subsequent
      thromboembolism.

PMID- 9165595
TI  - Squamous cell carcinoma of the prostate.
AB  - A primary squamous cell carcinoma occurring in the prostate is described. Local
      irradition, systemic anticancer chemotherapy using bleomycin and intraarterial
      administration of cis-platinum were done. Twenty-one months after the initial
      diagnosis there is no sign of tumor progression.

PMID- 9165596
TI  - Physiological background of enuresis type I. A preliminary report.
AB  - The physiological background of enuresis Type I, which is due to a mild arousal
      dysfunction, has been investigated in two studies, one in rats and one in
      children with Type I enuresis. The results of these investigations suggest that
      in this type of enuresis, the fundamental arousal function following bladder
      distension, due to an arousal centre like the locus coeruleus and its network, is
      normal. In contrast, the process of multiplying the transient connection from
      light sleep to complete awakening, which probably relies upon functions of the
      thalamus and the further upper centrums, was thought to be abnormal.

PMID- 9165597
TI  - Clinical enuresis phenotypes in familial nocturnal enuresis.
AB  - The objective of the current study was to identify the associations between
      phenotype and genotype in children with nocturnal enuresis. Of the total of 167
      wetting children, aged 5-10 years, without neurological or structural forms of
      incontinence, 110 were nocturnal enuretics. The examinations included a full
      psychiatric and psychological assessment, a paediatric and neurological
      examination, a family history with pedigree, ultrasonography, uroflowmetery,
      urinanalysis and bacteriology. Children with secondary nocturnal enuresis (n =
      28) had a significantly higher rate of behavioural disorders, life events and
      continuous psychosocial stress than those with primary nocturnal enuresis (n =
      82). Of the latter group, children with primary monosymptomatic nocturnal
      enuresis (n = 50) had an especially low rate of behavioural problems, when in
      comparison to primary non-monosymptomatic nocturnal enuretics (n = 32). Formal
      genetics point to a high genetic predisposition to nocturnal enuresis in all
      subgroups. Linkage studies to markers on chromosomes 8, 12 and 13 demonstrate
      both clinical, as well as genetic heterogeneity in nocturnal enuresis.

PMID- 9165598
TI  - Nocturnal enuresis in Hong Kong: different Chinese phenotypes.
AB  - Extensive studies of the epidemiology of nocturnal enuresis (NE) in Western
      countries indicate that the prevalence of this condition is relatively high (7
      10% of children aged 7 years are enuretic). In the current study, questionnaires
      to assess the epidemiology of NE in Hong Kong were completed by 3521 school
      children, aged 4-12 years, the majority of whom (99.8%) were ethnic Chinese.
      Analysis of these questionnaires revealed a lower prevalence of monosymptomatic
      NE in this population of children (3.5%) compared with the results of studies
      conducted in Western countries. Furthermore, NE was found to be associated with
      arousal difficulties, nightmares, a positive family history of enuresis, poor
      school performance and poor relationships with classmates. A second study
      conducted to evaluate the response to desmopressin treatment of 25 children with
      severe monosymptomatic NE showed that 84% had a good response (> 50% reduction in
      the number of wet nights). Taken together, the results of these studies suggest
      that children with NE in Hong Kong may represent a more homogeneous population
      than in other countries, and that there is a strong genetic component in the
      aetiology of NE in this country. These children appear to be particularly
      responsive to treatment with desmopressin.

PMID- 9165599
TI  - The enuretic episode--a complete micturition from a bladder with normal capacity?
      A critical reappraisal of the definition.
AB  - Fifty-five normal children, aged between 7 and 12 years, were hospitalised for
      four consecutive nights. On three of these nights, the subjects received 25 ml/kg
      body weight of fluid prior to bedtime. Such fluid-loading provoked 28 enuresis
      like episodes in 17 children, most of which occurred during the first few hours
      of sleep. The incidence of these enuretic events decreased with increasing age,
      more boys than girls were affected, there was a statistically significant
      correlation between total enuresis volume and nocturia volume, and the
      micturition was frequently incomplete, leaving large volumes of residual urine in
      the bladder. It was concluded that if nocturnal urine production exceeds bladder
      capacity, enuresis may be provoked, even in children who do not normally wet the
      bed. Furthermore, the definition of nocturnal enuresis as a complete emptying of
      the bladder during sleep may need revision.

PMID- 9165601
TI  - The effect of the full bladder on vasopressin secretion in healthy young adults.
AB  - Interactions between the central nervous system, bladder and kidneys have been
      investigated for many years in animal studies and have shown that bladder
      distension, in animals, leads to decreased urine production. The objectives of
      the current study were to determine the effect of a full bladder on urinary
      output, vasopressin secretion and urine osmolality in humans. The study involved
      healthy volunteers. They were studied for a period of 48 hours. This period
      included two 24-hour studies, one involving regular and frequent voidings (to
      produce a minimal bladder filling) and the other voiding postponement (to produce
      maximal bladder distension). In contrast to enuresis studies a circadian rhythm
      of vasopressin secretion was observed in the males involved in this study,
      whereas no significant rhythm of vasopressin secretion could be detected in the
      female subjects. However, this study was unable to confirm that, in humans, a
      full bladder causes a decrease in urine production, an increase in vasopressin
      secretion or an increase in urine osmolality.

PMID- 9165600
TI  - Long-term home studies of water balance in patients with nocturnal enuresis.
AB  - A 2-week, home-based study was conducted on 75 children with nocturnal enuresis
      to monitor the frequency of enuretic episodes and the volume of nocturnal urine
      production. The objectives of the study were to correlate nocturnal urine
      production to the occurrence of nocturnal enuresis and response to desmopressin
      (Minirin, DDAVP) treatment. Furthermore, patient compliance was evaluated.
      Enuresis episodes and nocturnal urine production was recorded every night during
      two base-line weeks without treatment and during 2 weeks with 20-40 micrograms
      desmopressin at bedtime. During both periods fluid intake and micturition volumes
      were recorded for 2 days. Desmopressin response was defined as > 50% reduction in
      wet nights during treatment. It was found that patient compliance was acceptable
      in most patients. Regarding urine output it was found that base-line nocturnal
      urine production was significantly higher during nights when enuresis occurred
      than during "dry" nights and significantly higher in desmopressin responders
      compared with desmopressin non-responders. During treatment with desmopressin,
      nocturnal urine production in desmopressin responders decreased to levels similar
      to those of non-responders. The results confirm inpatient circadian studies of
      urine output and emphasise the importance of nocturnal polyuria in patients with
      monosymptomatic enuresis. The response to desmopressin was found to correlate
      with the occurrence of nocturnal polyuria. Home studies were considered to be a
      useful tool in the characterisation of patients with nocturnal enuresis.

PMID- 9165602
TI  - Do aquaporins have a role in nocturnal enuresis?
AB  - Aquaporins are proteins that mediate transmembrane water transport in a variety
      of tissues including the kidney. Vasopressin plays an important role in
      regulation of water metabolism, and under normal conditions the kidney collecting
      duct is extremely sensitive to vasopressin. Vasopressin stimulates the synthesis
      of aquaporin 2 (AQP2) in kidney collecting duct principal cells. Studies in
      Brattle Boro rats which are vasopressin deficient, revealed low levels of AQP2 in
      association with extreme polyuria. After vasopressin treatment for 5 days AQP2
      levels increased threefold. Using rat models with nephrogenic diabetes insipidus
      (NDI) we have demonstrated that AQP2 expression is down regulated in association
      with polyuria, suggesting that reduced levels of AQP2 may be a general factor in
      acquired forms of NDI from a variety of reasons. The polyuria and urinary
      concentrating defects associated with an abnormal nightly-increase in AVP in
      patients with nocturnal enuresis may partly be due to a lack of vasopressin
      mediated AQP2 expression since treatment with desmopressin in these patients have
      normalised their nocturnal urine production.

PMID- 9165603
TI  - Are repeated desmopressin treatment attempts successful?
AB  - The efficacy of repeated treatment attempts using desmopressin (Minirin, DDAVP),
      either alone, alternately or in combination with an alarm device, were evaluated
      in 96 patients with primary nocturnal enuresis who were slow, delayed or non
      responders to therapy. At follow-up, 52% of the patients were cured and off
      therapy, an additional 26% had achieved dryness when using desmopressin regularly
      or on special occasions, and 22% were still wetting. It can be concluded that
      desmopressin therapy can be successfully commenced at the age of 5 years.
      Repeated treatment attempts can lead to achievement of dryness at an earlier
      stage. However, they probably do not influence the final outcome.

PMID- 9165604
TI  - Genetic factors as predictors for desmopressin treatment success.
AB  - The significance of a positive family history in predicting responsiveness to
      desmopressin (DDAVP) treatment was evaluated in 71 children with nocturnal
      enuresis. A good response to treatment was recorded in 91% of those children with
      a positive family history compared with only 7% of those with a negative family
      history. A review of the published literature further supports the predictive
      value of a positive family history and also confirms the importance of a broad
      definition for family history-including persistent nocturia. The importance of
      defining the family history is also discussed in terms of response to some other
      therapies for nocturnal enuresis.

PMID- 9165605
TI  - Spot urine osmolality, age and bladder capacity as predictors of response to
      desmopressin in nocturnal enuresis.
AB  - The objective of the current study was to find a cost-effective way of
      correlating spot urine osmolalities, bladder capacity and age in patients with
      monosymptomatic nocturnal enuresis with response to treatment with desmopressin
      (Minirin, DDAVP). A total of 35 children fulfilled the entry criteria and were
      included in the study. Constipation was eliminated in these children by
      appropriate enema treatment and diet adjustment prior to enrollment. Urine
      samples were collected at home at times that would best reflect fluctuations in
      plasma vasopressin levels (08:00, 16:00 and 22:00) over three consecutive 24-hour
      periods. Maximal functional bladder capacity was determined from the largest
      voided volume. A 2-week dose-titration treatment period with intranasal
      desmopressin was then conducted. With doses of desmopressin being increased by 10
      micrograms every 3 days. Response to desmopressin treatment was then assessed and
      factors that were observed to be markers of a favourable response were noted. Of
      the 35 children, 27 demonstrated a complete response to desmopressin treatment,
      at doses of 10-30 micrograms. Spot urine osmolalities were not predictive of the
      response to desmopressin (P > 0.1). In contrast, there was a significant
      correlation between a high maximum functional bladder capacity and response to
      desmopressin (P = 0.006). Age was also predictive of a good response to
      desmopressin treatment (P = 0.008).

PMID- 9165606
TI  - Differential diagnoses for nocturnal enuresis.
AB  - The symptom of nocturnal enuresis can be a feature of many conditions, including
      renal, neurological and organic disease states. It is important to differentiate
      primary nocturnal enuresis from secondary enuresis and from daytime incontinence
      with a nocturnal component. It is recommended that the routine investigation of
      enuretic children should comprise four components: structured interview, physical
      examination, urinalysis and ultrasound investigation. Additional intensified
      diagnostic and invasive procedures should be reserved for patients with suspected
      neurological disorders or urological dysfunction.

PMID- 9165607
TI  - Desmopressin tablet treatment: factors influencing gastrointestinal absorption.
AB  - The effect of food ingestion on the gastrointestinal absorption and antidiuretic
      action of oral desmopressin (Minirin, DDAVP) was assessed in 16 healthy
      volunteers, aged 20-35 years. The gastrointestinal absorption of desmopressin was
      reduced and delayed if administered with or 90 minutes after a meal, but this did
      not influence the antidiuretic action of the drug, at least for the first 3 hours
      following desmopressin administration.

PMID- 9165608
TI  - Bioavailability and pharmacokinetics of desmopressin in elderly men.
AB  - The bioavailability and pharmacokinetics of desmopressin (Minirin, DDAVP) have
      been studied in elderly males, aged between 55 and 75 years. In a four-way
      randomised study, subjects received a dose of desmopressin either intravenously
      (2 micrograms) or orally (200 micrograms) and either at 11 am or 10 pm. Daytime
      and night-time urine samples were collected both with and without desmopressin
      treatment. Intravenous doses of desmopressin were observed to have a longer
      duration of action than when the dose was given orally. These differences in
      efficacy may be attributable to differences in the bioavailability of
      desmopressin after intravenous or oral treatment.

PMID- 9165609
TI  - Prognostic factors for alarm treatment.
AB  - A review of the literature concerning the use of enuresis alarms highlighted the
      lack of standardised definitions used to define enuresis and the insufficient
      understanding of the working mechanisms of alarms. Although first reported in
      1904, enuresis alarms were not in routine use until the 1930's. Sensors in the
      bed or underwear, in conjunction with audible warning devices are the most common
      types of alarms. The alarm success rate of approximately 75% is independent of
      the type of alarm and there is a low relapse rate. In predicting alarm response,
      studies utilizing multivariate analysis techniques are superior to univariate
      techniques, but no one or combination of predictor variables is currently known
      to predict outcome accurately enough to alter standard clinical decision making.
      It is imperative that definitions are standardized and that study protocols are
      applied uniformly to well-defined populations that have a better potential
      response to enuresis alarms-the best intervention currently available.

PMID- 9165610
TI  - Alarm treatment: influence on functional bladder capacity.
AB  - Home recordings were used to study the effect of alarm treatment, over a period
      of 6 weeks, in children with monosymptomatic nocturnal enuresis. Vasopressin
      day/night ratios were shown to be a good indicator of alarm treatment success.
      Serial measurement of plasma vasopressin levels is, however, unsuitable for use
      in the clinic, as extensive analyses would have to be performed to obtain the
      necessary results. Use of an alarm increased nocturnal bladder capacity, but had
      no effect on daytime bladder capacity, sleep patterns, vasopressin secretion,
      nocturnal urine output or pelvic floor activity. In addition, the results of the
      study suggest that an alarm treatment period of 2 months would lead to more
      successful results than the 6 weeks used in the study.

PMID- 9165611
TI  - Combination therapy for nocturnal enuresis with desmopressin and an alarm device.
AB  - The efficacy of alarm monotherapy (35 children) was compared with the efficacy of
      alarm treatment in combination with 40 micrograms desmopressin (Minirin, DDAVP)
      nasal spray (36 children). At the end of the treatment period, children receiving
      combination therapy had more dry nights per week (mean: 6.1) than children using
      an alarm alone (mean: 4.8). In addition, more children achieved an initial
      success (4 weeks of dryness) following combination treatment (27 children [75%])
      compared with alarm monotherapy (16 children [46%], P < 0.005). This improvement
      with alarm plus desmopressin was particularly pronounced in children with severe
      wetting (> or = 6 nights per week), family problems or behavioural problems. It
      may, therefore, be appropriate to manage children in these categories with an
      enuresis alarm supplemented with desmopressin to improve treatment outcome.

PMID- 9165612
TI  - Nocturnal enuresis: economic impacts and self-esteem preliminary research
      results.
AB  - Bedwetting is a common complaint, affecting approximately 10% of 7-year old
      children in the developed world and causing an economic drain on society. Not
      only is the cost of nocturnal enuresis borne by the families, but also by
      national health services and state health insurance. Although previous studies
      have examined the direct costs of nocturnal enuresis, the current paper also
      investigates the indirect costs to some selected families, such as the extra
      housework that is involved. The total cost of having an enuretic child was
      estimated on a case study basis in five countries with results being reported
      here for three countries (Sweden, UK and Germany). The study considered costs
      over a period of 3 months, with questionnaires on self-perceived self-esteem
      being included for the child. The critical factors influencing overall costs were
      the number of wet nights per week, necessitating washing and drying, and the
      costs of the treatment itself. Overall, the study found that total costs of not
      treating enuresis in heavy bedwetters can be higher than with any of the
      treatment alternatives, which must be seen as an additional burden to families
      with a child suffering from lower self-esteem.

PMID- 9165613
TI  - The concept of outcome.
AB  - The Enuresis Resource and Information Centre in the UK has recently launched a
      second edition of Guidelines on Minimum Standards of Practice in the Treatment of
      Enuresis. The purpose of the Guidelines is to provide a blueprint for service
      delivery in the UK, leading to enuresis services that offer effective, accessible
      and dependable treatment. In particular, these Guidelines propose minimum and
      target standards that enuresis services should aim to achieve, relating to
      referral, assessment and treatment, as well as catchment area appointments,
      research and referral. In addition, the Guidelines may be used to provide a
      framework within which enuresis services can be audited and evaluated. Successive
      cycles of observation, appraisal and action should encourage a continual
      improvement process in each clinic, resulting in a progressive development of the
      service offered.

PMID- 9165614
TI  - What is an acceptable treatment outcome?
AB  - Nocturnal enuresis is a multifactorial condition and, as such, is accessible to a
      variety of treatment modalities. In order to evaluate and compare the efficacies
      of different treatments in patients with specific pathophysiologies, studies
      should describe fully the patient population under investigation. In addition,
      many of the studies conducted to date have applied different outcome measures,
      making comparisons difficult. Therefore, it is necessary to define standard
      outcome measures that should be used universally. These may relate to the effect
      of the treatment on the number of wet nights per week, the effect on the family
      economy of a reduction in the number of episodes of enuresis and the effect on
      the child's self esteem and/or quality of life.

PMID- 9165616
TI  - Cells and cell junctions in the muscle coat of the bladder.

PMID- 9165615
TI  - Self-esteem before and after treatment in children with nocturnal enuresis and
      urinary incontinence.
AB  - A case control study was designed to study self-esteem in children with nocturnal
      enuresis and daytime incontinence. The patients and the controls were recruited
      from the normal population in the town of Umea, Sweden. Medical and psychological
      examinations were performed before the start of treatment. Follow up
      investigations were carried out at 3 and 6 months after starting treatment. Self
      esteem was measured using a Swedish self-answering questionnaire that was known
      to have good psychometric properties. Statistically significant impairment of
      self-esteem was observed between patients and control children before starting
      treatment (P < 0.001). After 6 months treatment, the patients had the same levels
      of self-esteem as the control group. Self-esteem was significantly better in
      patients that were totally dry at 6 months follow up compared with the patients
      with persisting urinary problems (P < 0.01). Children from lower socioeconomic
      groups were found to have lower self-esteem than children from higher
      socioeconomic groups; boys were also found to have lower self-esteem than girls.

PMID- 9165617
TI  - Initiation of contraction in detrusor smooth muscle.

PMID- 9165618
TI  - The physiological mechanisms involved in bladder emptying.

PMID- 9165619
TI  - Change in length of the detrusor muscle cells.

PMID- 9165620
TI  - The collagens and their urologic significance.

PMID- 9165621
TI  - The concept of bladder work: work and power in bladder emptying.

PMID- 9165623
TI  - Alterations in the physiological properties of urinary bladder smooth muscle
      caused by bladder emptying against an obstruction.

PMID- 9165622
TI  - Etiology of bladder dysfunction secondary to partial outlet obstruction. Calcium
      disregulation in bladder power generation and the ability to perform work.
AB  - Similar to all smooth muscle, contraction of urinary bladder smooth muscle
      depends upon a rise in intracellular free calcium, which results from both
      calcium influx from extracellular spaces and calcium release from intracellular
      stores (calcium-induced calcium release [CICR]). Recent studies from our
      laboratory demonstrate that one of the major dysfunctions induced by partial
      outlet obstruction is a marked reduction in the participation of CICR (from IP3
      sensitive and IP3-insensitive sites on the sarcoplasmic reticulum [SR]) during
      stimulation by both field stimulation (neurotransmitter release) and by direct
      muscarinic stimulation (bethanechol). Experimentally, rabbit urinary bladder
      function can be evaluated using an isolated whole bladder model. The current
      study utilizes the isolated whole bladder model to compare the effects of partial
      outlet obstruction on the responses to field stimulation and bethanechol with the
      responses of normal bladders following inhibition of CICR with the combination of
      thapsigargin+ryanodine. The parameters measured include the magnitude of pressure
      generation, rate of pressure generation, time to maximal pressure generation,
      percent volume emptied, rate of emptying, power generation, and work performed
      (both total work and work per ml emptied). Partial outlet obstruction resulted in
      virtually identical alterations in the responses of the bladder to stimulation
      (field stimulation and bethanechol) to that of inhibition of CICR by
      thapsigargin+ryanodine. Thus, these studies provide strong support for our
      hypothesis that the contractile dysfunctions secondary to partial outlet
      obstruction are directly related to a marked inhibition of the CICR component of
      the response to both field stimulation and bethanechol.

PMID- 9165624
TI  - Changed metabolism of detrusor muscle cells from obstructed rat urinary bladder.

PMID- 9165625
TI  - Contractile protein changes in urinary bladder smooth muscle during obstruction
      induced hypertrophy.

PMID- 9165626
TI  - Emptying against outflow obstruction--pharmacological aspects.
AB  - Outflow obstruction induces changes in muscarinic and adrenergic receptor
      functions, and in non-adrenergic, non-cholinergic (NANC) mechanisms relevant for
      detrusor contraction and relaxation. The complexity of the muscarinic regulation
      of detrusor function makes the relative importance of the different muscarinic
      receptor subtypes difficult to assess, both in the normal and obstructed
      detrusor. This means that the optimal profile of subtype selectivity of
      antimuscarinic drugs meant for treatment of detrusor overactivity still remains
      to be established. In most animal species, detrusor contraction is mediated by
      both muscarinic and NANC mechanisms. The most likely transmitter responsible for
      the NANC-component of contraction is ATP. NANC-components are probably of minor
      importance in the normal human detrusor. However, if the importance of the ATP
      dependent component of contraction increases in the obstructed detrusor, this may
      have therapeutic implications. In normal human detrusor, alpha-adrenoceptors seem
      to have no significant role in the contractile activation. However, the
      effectiveness of alpha-adrenoceptor antagonists on storage symptoms, and,
      occasionally, on urodynamically proven detrusor instability, in patients with
      outflow obstruction, suggests an involvement of alpha-adrenoceptors. The
      functional importance of beta-adrenoceptors for the obstructed detrusor function
      remains to be settled. In outflow obstruction, changes in the excitability of the
      detrusor smooth muscle may occur that predisposes for detrusor overactivity.
      Drugs acting at K+ channels can decrease detrusor excitability, and may, if
      cardiovascular side effects can be avoided, represent a novel, promising way of
      treating detrusor overactivity.

PMID- 9165627
TI  - At issue: speech fluency and schizophrenic negative signs.
AB  - The spontaneous speech of negative-syndrome schizophrenia patients is
      underproductive and contains many hesitations and pauses. Acoustic analysis of
      the patient's speech during interview reveals that the duration of pauses,
      independent of other linguistic or paralinguistic measures, correlates strongly
      with the clinician's impressions of the patient's flat affect and alogia. Pausing
      is less related to associality and other aspects of the negative syndrome. The
      hesitations appear to reflect a word-finding difficulty that, together with
      neuropsychological evidence of compromised performance on word fluency tasks,
      suggests a specific speech generation difficulty. The significant relationship
      between pausing and both flat affect and alogia suggests that the two negative
      signs share phenomenal and psychometric properties. The examination of speech
      generation mechanisms may provide an informative avenue for study of
      schizophrenic psychopathology. Acoustic analysis reveals processes that are not
      apparent to the clinician and may provide a useful basis for clinical assessments
      and research.

PMID- 9165628
TI  - Substance abuse and schizophrenia: editors' introduction.
AB  - Most individuals with schizophrenia have problems with abuse of substances
      ranging from licit substances, such as nicotine, to illicit ones, such as
      cocaine. This comorbidity may reflect self-medication, as well as a biological
      susceptibility to both disorders. Twin studies have suggested that this
      biological susceptibility may involve genetic factors. Other biological risk
      factors may involve the medications used to treat schizophrenia, which may
      produce symptoms that provoke abuse of drugs to relieve negative symptoms or may
      even enhance the euphoric response to abused drugs. The articles in this issue
      address several research areas related to substance abuse and schizophrenia,
      including the differential diagnosis of schizophrenia and organic disorders
      induced by substance abuse and the impact of substance abuse on the course of
      early schizophrenia. The management of substance-abusing schizophrenia patients
      requires a careful balance of pharmacotherapy and psychotherapies, and atypical
      antipsychotic agents may be particularly helpful. Psychotherapy needs to focus
      both on the management of affect and on the adequate monitoring of drug
      abstinence.

PMID- 9165629
TI  - Differential diagnosis of substance-induced psychosis and schizophrenia in
      patients with substance use disorders.
AB  - We derived a statistical model that discriminates between substance-induced
      psychosis (i.e., DSM-III-R organic delusional disorder or organic hallucinosis;
      ODD-OH) and DSM-III-R schizophrenia in patients who have both DSM-III-R
      psychoactive substance use disorders (PSUD) and prominent delusions or
      hallucinations. A sample of 211 PSUD inpatients was divided by year of admission
      into data sets A and B, each of which was divided between those with concurrent
      schizophrenia and those with concurrent ODD-OH. A six-predictor discriminant
      function correctly classified 76.2 percent of all set A patients, including 83.1
      percent with schizophrenia. Formal thought disorder and bizarre delusions
      significantly predict a diagnosis of schizophrenia, with odds ratios (OR) of
      3.55:1 and 6.09:1, respectively. Suicidal ideation (OR = 0.32:1), intravenous
      cocaine abuse (0.18:1), and a history of drug detoxification (0.26:1) or
      methadone maintenance (0.18:1) demonstrate inverse relationships with a
      schizophrenia diagnosis. The model was validated in set B, correctly predicting
      the diagnostic status of 70.4 percent of patients (72.5% with schizophrenia). The
      pattern of presenting symptoms and clinical history differs in patients with
      psychosis due to PSUD and in those whose psychosis is due to schizophrenia. The
      model presented here contributes to the differential diagnosis of schizophrenia
      and ODD-OH among patients with PSUD.

PMID- 9165630
TI  - Substance use disorder and the early course of illness in schizophrenia and
      affective psychosis.
AB  - The relationship between a history of substance use disorder and the early course
      of psychotic illness was examined in 96 subjects with schizophrenia and 106
      subjects with affective psychosis followed in the Suffolk County Mental Health
      Project, a longitudinal study of first-admission psychosis. Subjects received a
      structured diagnostic interview and clinical ratings at baseline assessment and
      again 6 months later. The 6-month assessment included information about treatment
      received during the interval. A lifetime history of substance use disorder was
      associated with worse clinical functioning at 6 months for schizophrenia
      subjects, but not for those with affective psychosis. There were no significant
      associations of substance use disorder with type of treatment during the interval
      or with self-reported compliance with medication. Schizophrenia subjects were
      more likely than subjects with affective psychosis to report cannabis use during
      the interval and to meet criteria for cannabis use disorder.

PMID- 9165631
TI  - Enhanced neurobehavioral effects of cocaine with chronic neuroleptic exposure in
      rats.
AB  - Individuals with schizophrenia are often treated with medications that block
      dopamine (DA) neurotransmission. Chronic administration of many DA antagonists
      alters dopaminergic function, causing a supersensitivity to DA agonists. Because
      the DA agonist properties of cocaine seem to be involved in its behavioral
      effects, chronic DA antagonist treatments may enhance these effects of cocaine.
      This article presents evidence to support this hypothesis, as well as its
      implications for treating schizophrenia patients who abuse cocaine and
      suggestions for future research.

PMID- 9165632
TI  - Pharmacotherapy of schizophrenia patients with comorbid substance abuse.
AB  - Substance abuse worsens the course of schizophrenia and significantly impairs the
      relationship between the patient and the health care team. Recent advances in
      laboratory studies of substance abuse and the pharmacology of schizophrenia open
      up new possibilities for pharmacotherapy of substance abuse in schizophrenia
      patients. D1 dopaminergic receptor agonists may directly block the drive for
      stimulant use. D2 dopaminergic receptor antagonists may indirectly block the
      drive for stimulant and nicotine use, while opioid antagonists appear to reduce
      the drive to use alcohol. New generations of neuroleptics with serotonin (5-HT2)
      receptor antagonism and/or 5-HT1A agonist activity may reduce substance abuse in
      schizophrenia patients who self-medicate negative symptoms or neuroleptic side
      effects. Pharmacotherapy efficacy may be enhanced by adding contingency
      management, social skills training, and other manualized programs. Tables are
      provided of potentially useful medications. Preliminary results are presented of
      cocaine-abusing schizophrenia patient treated with desipramine and traditional
      neuroleptics.

PMID- 9165633
TI  - Motivation to quit using substances among individuals with schizophrenia:
      implications for a motivation-based treatment model.
AB  - Although the motivation to quit using substances is an important prognostic and
      treatment-matching factor in substance abuse treatment, there is limited
      information on motivation to quit among individuals with schizophrenia. This
      study used the five-stages-of-change model to evaluate the motivational levels of
      497 individuals with schizophrenia or schizoaffective disorder in an outpatient
      mental health clinic. Rates of substance abuse, motivation levels to quit each
      specific substance, and correlates to motivational levels were evaluated. At
      least one substance use disorder was diagnosed in 224 of the subjects (45%);
      however, there was significant variability among the caseloads of the outpatient
      division teams. The patients in the triage/acute services and community outreach
      teams had substance abuse rates of about 70 percent. Most subjects had low
      motivation to quit substances, and the rates varied according to substance (range
      of 41% for opiates to 60% for cocaine). Treatment-matching strategies are
      suggested in the motivation-based treatment model.

PMID- 9165634
TI  - Illness severity and treatment services for dually diagnosed severely mentally
      ill outpatients.
AB  - This study of a frequently endorsed, but untested, model of outpatient treatment
      for persons with coexisting severe mental illness and substance use disorders
      assessed how the amount of treatment services delivered was related to an
      individual's global severity of illness, whether different modes of treatment
      were related to different aspects of illness, how noncompliance with treatment
      was related to the severity of illness and amount of services delivered, and how
      the diagnosis of schizophrenia/schizoaffective influenced these issues.
      Participants with high total severity of illness (TSI) received about twice the
      number of appointments (20.7 vs. 12.3) per month as those with low TSI scores.
      Higher TSI was also related to a DSM-IV diagnosis of
      schizophrenia/schizoaffective, being in a lower "phase" of treatment,
      representative payee benefit management, homelessness, and more hospitalizations.
      Participants with higher psychiatric symptom severity received significantly more
      case management and medication services, but not group therapy or day treatment.
      Severity of substance use condition was significantly related only to case
      management. This model of treatment was found to be successful in delivering
      higher levels of treatment services to those needing them.

PMID- 9165635
TI  - Schizophrenia and nicotine use: report of a pilot smoking cessation program and
      review of neurobiological and clinical issues.
AB  - Nicotine use is a major public health problem that increases medical morbidity
      and mortality. Nicotine's action and the pathobiology of schizophrenic disorders
      have common neurobiological substrates. Tobacco smoking alters medication blood
      levels and effectiveness, modifies psychiatric symptoms, and is a clue for other
      substance abuse. This article presents an evaluation of a smoking cessation
      program for 24 smokers with schizophrenia. Fifty percent completed the program,
      40 percent decreased use by 50 percent, and 13 percent remained abstinent (carbon
      monoxide verified) for 6 months. Nicotine replacement, motivational enhancement
      therapy, and relapse prevention behavioral therapy were important components of
      treatment. Pharmacotherapy strategies of a higher-dose nicotine patch, combining
      nicotine gum and a patch, and augmentation medication to nicotine replacement
      should be evaluated in future studies in this population.

PMID- 9165636
TI  - Anomalous cerebral asymmetry and language processing in schizophrenia.
AB  - Reversal or reduction of normal structural cerebral asymmetries may be related to
      the pathogenesis of schizophrenia, but this relationship remains controversial.
      We review the literature and describe a further study designed to detect whether
      anomalous asymmetries are present early in the illness (at the first episode),
      whether they predict deficits in language processing, and whether they may be
      related to a genetic predisposition for schizophrenia. Asymmetries of brain
      widths and segments of the sylvian fissure were assessed in a magnetic resonance
      imaging study of 87 patients with a first episode of schizophrenia and 52 normal
      controls. These asymmetries were correlated with specific measures of language
      processing, memory, and hand skill. An independent group of 14 pairs of siblings
      with schizophrenia were also evaluated for evidence of heritability to cerebral
      asymmetries. Width asymmetries were reduced in patients compared with controls in
      the posterior (p = 0.02) and occipital (p = 0.05) regions. Brain horizontal
      length, on the other hand, was significantly more asymmetrical in patients (left
      > right; p = 0.04). For sylvian fissure measurements, asymmetries in controls
      (left > right) were greatest for the horizontal component; this asymmetry tended
      to detect differences in patients by comparison with controls (p < 0.06). In a
      range of tests of language and memory, few significant correlations between
      performance and cerebral asymmetries were detected either in patients or
      controls, although patients consistently scored poorer than controls in the
      majority of tests. In 14 pairs of psychotic siblings, within-pair correlations
      for the horizontal sylvian fissure asymmetry were significantly greater than
      between-pair correlations. These findings are consistent with the early presence
      (possibly genetic) of anomalous cerebral asymmetry. However, the functional
      correlates of reduced asymmetry remain obscure.

PMID- 9165637
TI  - Longitudinal courses of thought disorder in schizophrenia and schizoaffective
      disorder.
AB  - This research examined the longitudinal courses of thought disorder in
      schizophrenia, schizoaffective disorder, and other psychotic and nonpsychotic
      disorders. One-hundred-eighty young psychiatric inpatients were prospectively
      diagnosed at an early stage of illness and followed up and evaluated for thought
      disorder at 2, 4.5, and 7.5 years post-index hospitalization. Patterns of thought
      disorder were examined in relation to diagnosis, index thought disorder,
      demographic characteristics, prognostic factors, clinical states of psychosis,
      outcome at followup, and treatment. Courses of frequent and persistent thought
      disorder were most frequently found in schizophrenia. The prevalence and course
      of thought disorder over time in schizoaffective disorder laid between those in
      schizophrenia and those in other psychotic disorders. Demographic factors were
      not predictive of the course of thought disorder. Diagnosis, the presence of
      thought disorder at index, pre-index work and academic competence, and pre-index
      social functioning were associated with courses of thought disorder (when courses
      were classified as remitted/infrequent and frequent/persistent). The longitudinal
      relationships between thought disorder and psychosis suggested that, in
      schizophrenia, thought disorder is not simply a function of psychosis. Thought
      disorder appeared more closely tied to the presence of psychosis over time in
      schizoaffective disorder. Increased inquiry into the factors associated with
      different courses of thought disorder across psychiatric disturbances appears
      merited.

PMID- 9165638
TI  - Course and outcome for schizophrenia versus other psychotic patients: a
      longitudinal study.
AB  - We studied 276 patients longitudinally, beginning at the acute phase and
      continuing at three successive followups over 7.5 years, comparing 74
      schizophrenia patients with 74 other psychotic patients and 128 nonpsychotic
      patients on early course and outcome. Schizophrenia patients showed significantly
      poorer functioning than patients with other psychotic disorders at each of the
      three followups (p < 0.05). More schizophrenia patients than other psychotic
      patients showed consistent psychopathology and a course in which there was not
      complete remission at any of the three followups (p < 0.05). Most schizophrenia
      patients did not show severe decrements in social activity level. Poor outcome
      schizophrenia patients showed significantly slower recovery at each followup than
      did other psychotic patients with initial poor outcomes (p < 0.01). The results
      indicate that, during the early course, schizophrenia patients still show
      relatively poor outcomes, although a small number of schizophrenia patients enter
      into complete remission. Over time, many schizophrenia patients fluctuate between
      severe disability and moderate disability rather than always showing severe
      disability. Schizophrenia patients tend to recover more slowly then other
      psychotic patients. Differences between schizophrenia patients and other
      psychotic patients in clinical course over time may be larger than differences at
      any single followup.

PMID- 9165639
TI  - Cross-ethnic symptom differences in schizophrenia: the influence of culture and
      minority status.
AB  - The two objectives of this tri-ethnic study were (1) to test competing hypotheses
      from the minority status and ethnic culture perspectives in examining cross
      ethnic symptom differences in schizophrenia and (2) to test cultural mediators of
      the symptom differences. Analyses were done on samples of minority (African
      American and Latino) and nonminority (white) groups. Hypothesized cross-ethnic
      symptom differences were tested, and indicators of sociocentricity were examined
      as cultural mediators of symptom differences. The sample consisted of 184
      individuals (51.6% white, 32.6% African-American, 15.8% Latino, 75% male)
      diagnosed with schizophrenia in an outpatient, urban setting. Symptom variables
      were obtained from the Brief Psychiatric Rating Scale and the Quality of Life
      Scale. Two sociocentric indicators (empathy and social competence) were used to
      differentiate minority from nonminority groups. Multiple regression was used to
      test the mediational influence of the sociocentric indicators on the symptom
      differences. After controlling for social class, significant differences were
      found in eight symptom variables. These showed the nonminority group to be
      consistently more symptomatic than the ethnic minority groups, findings which
      supported the ethnic culture hypothesis. Sociocentric indicators were found to be
      significant mediators of the cross-ethnic symptom differences. This study
      supported the ethnic culture hypothesis, which predicted lower symptoms for the
      ethnic minority groups, and showed that sociocentric variables strongly mediated
      the more benign symptom profile for the ethnic minority groups. The study
      indicates that culture should be more fully integrated into current
      biopsychosocial models of schizophrenia.

PMID- 9165640
TI  - Clinical benefits of paid work activity in schizophrenia: 1-year followup.
AB  - In a previous article in the Schizophrenia Bulletin (Vol. 22, No. 1, 1996), we
      presented findings of a study on the clinical and rehabilitative effects of work
      activity on 150 subjects diagnosed with schizophrenia or schizoaffective
      disorder. Subjects were randomly assigned to either a Pay ($3.40/hr) or No-Pay
      group and given 6-month work placements in a Department of Veterans Affairs
      medical center. At the 5-month followup, Pay subjects had worked more hours and
      earned more money (from any employment) than No-Pay subjects. Pay subjects also
      had significantly greater improvement in symptoms and lower rehospitalization
      rates. Clinical improvement was closely linked to amount of participation. We
      concluded that pay increased participation. The current study examined clinical
      and rehabilitative outcomes at 1-year followup, 6 months after the conclusion of
      the work program. Results indicated that the Pay subjects had a significant
      decrease in work activity once they had completed the work program. However, 75
      percent of those who had fully participated in the program continued working
      during the subsequent 6 months, either as volunteers or for pay. Clinical
      outcomes for subjects in the Pay condition were attenuated at 1-year followup but
      still significantly better than for subjects in the No-Pay condition. More than
      40 percent of participants continued to be "much improved" on total symptoms, and
      more than 50 percent were "much improved" on positive symptoms. Discussion
      focuses on the importance and limitations of work for pay as a clinical
      intervention and concludes that continuous work services are necessary and
      beneficial for many people with schizophrenia.

PMID- 9165642
TI  - What do relatives of people with schizophrenia find helpful about family
      intervention?
AB  - While research indicates that family intervention is of benefit to schizophrenia
      patients and their relatives, it remains unclear why it is beneficial.
      Methodologies developed in psychotherapy process research may be of use in
      answering this question. The present study examines the applicability of one such
      methodology to a clinically based family intervention program. Relatives' (n =
      20) reports of what they found helpful and unhelpful about the program were
      examined and the perceived therapeutic impacts of the program are reported. The
      implications of these results for future research are discussed.

PMID- 9165641
TI  - Coping with negative symptoms of schizophrenia: patient and family perspectives.
AB  - An exploratory study was conducted of the strategies that schizophrenia patients
      and their relatives employ to cope with negative symptoms. Coping strategies and
      their perceived efficacy were elicited in semistructured interviews conducted
      separately with patients and relatives. Coping responses were coded according to
      the following dimensions: behavioral-cognitive, social-nonsocial, and problem
      focused-emotion focused. Overall, the number of coping strategies was related to
      perceived coping efficacy for both patients and relatives, regardless of the type
      of strategy. Perceived coping efficacy tended to be highest for apathy;
      intermediate for alogia, anhedonia, and inattention; and lowest for blunting.
      Relatives with more knowledge about schizophrenia used more coping strategies and
      reported higher levels of coping efficacy. Patient rejection by relatives and
      distress (either patient or relative) tended to not be related to coping
      strategies. The findings suggest that patients and relatives use a wide variety
      of strategies to cope with negative symptoms of schizophrenia. Future clinical
      work and research need to evaluate whether families may benefit from
      psychoeducational approaches to teaching them how to better manage negative
      symptoms.

PMID- 9165643
TI  - First person account: living with mental illness.

PMID- 9165644
TI  - How end-stage renal disease (ESRD)-Medicare developed.
AB  - Uremia is a chemical, toxic, potentially fatal condition. In a variable pattern,
      uremia ultimately kills almost every cell in the body. Uremia is produced by
      hundreds of diseases, both kidney and systemic (e.g., diabetes). These kinds of
      uremic conditions range from the acute and catastrophic to the slowly and
      moderately progressive. Humans and medicine have struggled at least since
      Hippocrates to understand, prevent and treat uremia and thereby prolong the
      useful lives of the young and the aging. Accelerated by the spectacle of
      premature uremic deaths from crush syndrome, shock, and forms of nephritis during
      major wars and disasters, medicine fused clinical and basic science with
      industrial technology and came up with two effective treatments. Dialysis in
      several modes and kidney transplantation became feasible but proved complex and
      expensive. How people, struggling to survive, were able to use a representative
      form of government to treat all kidney patients, forms a human story: A "people"
      story. Since it culminated within a single medical generation, it is possible to
      tell the story as a participant and eye-witness. This is how the medical, social
      and national organization of substitution therapy for uremia evolved. Since it is
      legislatively called end-stage renal disease, we titled the entitlement, "How
      ESRD-Medicare Developed."

PMID- 9165645
TI  - The legislative and regulatory process in the end-stage renal disease (ESRD)
      program, 1973 through 1997.
AB  - Although hemodialysis began in the early 1960s, it did not begin to really grow
      until 1973, when the Federal government started to pay for end-stage renal
      disease (ESRD) treatment under Medicare. Since then, the Health Care Financing
      Administration (HCFA) has made a series of mistakes while maintaining this very
      successful program. This article traces the steps HCFA took, and the responses by
      the providers that produced the situation we have today. This program pays the
      lowest amount for hemodialysis of any industrialized nation, and most likely as a
      result has the highest mortality rate (23%) of any of the same countries. The
      problem as outlined is that HCFA attempted to ration by price while ignoring
      quality. This has been compounded by the providers finding more and more ways to
      reduce cost to continue to make a profit while not improving quality. The result
      is a program that could have been much better, and a patient population that has
      suffered.

PMID- 9165646
TI  - An improved understanding of the causes of end-stage renal disease.
AB  - An understanding of the causes of end-stage renal disease (ESRD) is approached
      through a discussion of currently attributed causes, potentially unattributed
      causes, and the reasons for growth in new ESRD cases. The attributed causes of
      ESRD have varied over time and by region. In the United States, diabetes has long
      been the most common attributed cause of ESRD, accounting for 36% of incident
      cases in 1992. In contrast, diabetic ESRD is far less common in other countries.
      Hypertension and glomerulonephritis are the next most commonly attributed causes
      of ESRD, but these diagnoses are not necessarily based on consistent or uniform
      criteria. Mistaken classification of the cause of ESRD is possible in many cases.
      Emerging evidence suggests that other processes, including renovascular disease
      and analgesic ingestion, can cause or contribute to ESRD more often than they are
      recorded. The incidence of ESRD has been increasing at a rate of up to 9% per
      year. The likely reasons for ESRD growth include decreased competing risk from
      other diseases, increased referral and acceptance of patients with advanced renal
      failure, and increased renal disease.

PMID- 9165647
TI  - Options for renal replacement therapy: special considerations.
AB  - The number of patients coming to end-stage renal disease (ESRD) continues to
      increase annually, challenging the existing system of renal replacement therapy.
      Moreover, these patients, on average, are older at the onset of ESRD and are
      living longer after the initiation of renal replacement therapy. The choice of
      modality of renal replacement therapy (hemodialysis, peritoneal dialysis, or
      transplantation) that is best suited for a particular patient is thus
      increasingly important. Important factors to consider include not only mortality
      and morbidity, but also quality of life, patient age and social circumstances,
      and the etiology of ESRD. Three ESRD patient populations in particular, diabetic
      patients, the elderly and the patients with HIV infection or acquired
      immunodeficiency syndrome (AIDS), present renal care providers with complex
      issues as to renal replacement therapy and outcomes. Motivated patients with
      available resources, no matter what their cause of ESRD, should be considered as
      excellent candidates for home hemodialysis. This modality of renal replacement
      therapy is associated with improved survival and quality of life when compared
      with other modes of dialysis.

PMID- 9165648
TI  - Renal transplantation: a quarter century of achievement.
AB  - Renal transplantation has become the treatment of choice for most types of end
      stage renal failure. Immunosuppressive drug therapy has improved enormously over
      the past 25 years, and the advent of potent new drugs in addition to cyclosporine
      make multiple drug therapy for immunosuppression the direction of the immediate
      future. Monoclonal antibodies have so far had a limited role in
      immunosuppression, but are likely to prove of value in protocols aimed at
      inducing specific unresponsiveness to a renal allograft. This remains the goal of
      transplantation biology, because the long-term complications of all current
      nonspecific immunosuppressive protocols are formidable. In addition, the shortage
      of cadaver kidneys for transplantation has led to an increasing use of living
      related and unrelated donors, and stimulated a major research activity in
      xenotransplantation in an attempt to bring it to the clinic in the not too
      distant future.

PMID- 9165649
TI  - The hemodialysis membranes: a historical perspective, current state and future
      prospect.
AB  - Transport and biocompatibility characteristics are two important considerations
      when choosing hemodialysis membranes. Dialyzer performance depends on clearances
      of small solutes, middle molecules, and oncotically active proteins. Although
      complement and neutrophil activation have become the gold standards for
      biocompatibility testing of dialysis membranes, alterations of other cellular and
      noncellular blood elements as a result of blood-membrane interactions are also
      important. Because of concerns about middle molecule transport and
      biocompatibility, the original cellophane membrane has been gradually replaced by
      modified cellulosic membranes and synthetic membranes for clinical use. Recent
      studies suggest that the choice of dialysis membrane influences the clinical
      outcome of patients in several areas, including intradialytic acute anaphylactoid
      reactions, beta 2-microglobulin associated amyloidosis, recovery from acute renal
      failure, and mortality of chronic hemodialysis patients. However, the relative
      contributions of middle molecule transport, biocompatibility, and other factors
      in determining these differences in outcome are unclear. Future development of
      hemodialysis membranes should focus on improving biocompatibility and enhancing
      clearances of small solutes and middle molecules, while minimizing the loss of
      larger plasma proteins.

PMID- 9165650
TI  - Dialysis equipment and dialysate, past, present and the future.
AB  - From the beginning of the first described hemodialysis in 1889, history has shown
      an exponential evolvement of systems that have resulted in greater safety,
      efficiency, and broader utilization. It took 60 years, 1947, for the technology
      to be used in a clinical setting in North America, treating acute renal failure.
      Commercial interests became involved in the mid 1950s, resulting in the "twin
      coil" dialyzer, costing five times the current cost of similar membranes. The
      entry of commercial entities created a rapidly escalating technology in dialysis
      delivery systems to be used in the chronic recurring dialytic procedure: blood
      pumps, pressure monitors, needles, dialysate delivery, ultrafiltrate control,
      membrane design and configuration, dialysate composition. All of these have, for
      the most part, required trained staff and increasingly comfortable facilities to
      accommodate the rather static thrice-weekly hemodialysis procedure. The future
      will likely see more home dialysis, more frequent dialysis, better on-line
      monitoring, with attention to those factors which have allowed the greatest cause
      of morbidity, cardiovascular disease, to be controlled.

PMID- 9165651
TI  - End-stage renal disease: a proving ground for quality improvement in health care.
AB  - This article chronicles the health care quality improvement efforts that relate
      to patients with end stage renal disease (ESRD). The emphasis is on quality
      improvement as a management system as opposed to the quality improvements that
      resulted from strictly technical dialysis-related issues. The government has
      exercised considerable oversight on the ESRD program because of its growth and
      cost. History has shown that quality assurance (QA) has had little effect on
      improving quality or decreasing cost. The philosophy, methods, and tools of
      continuous quality improvement (CQI) have been shown to work in health care. CQI
      is a management system that offers hope for higher quality affordable health
      care. Computer technology is at last sophisticated enough to permit the
      collection of large amounts of clinical data at the point of care. This will
      permit CQI methods and tools to be applied generally at reasonable costs.
      Physicians in general and nephrologists in particular are beginning to understand
      the managed care environment. They are beginning to understand the paradigm shift
      that is required to effect the changes necessary for physicians to assume their
      leadership role in health care. This article reviews the quality efforts of the
      past and present. It discusses the strengths and weaknesses of efforts to improve
      quality and lastly presents a vision for the future.

PMID- 9165652
TI  - Peritoneal dialysis: an evolving understanding.
AB  - Since continuous ambulatory peritoneal dialysis (PD) was introduced in 1978 by
      Popovich and Moncrief, the use of peritoneal dialysis as effective renal
      replacement therapy has expanded on an international level. Improvements in
      technology and technique have lessened the incidence of infectious complications,
      although strategies continue to evolve to improve technical success. As technical
      challenges have been met, increasing attention has been turned to PD dose.
      Retrospective studies have strongly suggested that patient outcome is related to
      the amount of toxin removal. Recently, prospective data confirm that morbidity
      and mortality are strongly associated with dialysis adequacy. The important
      contribution of residual renal function to total toxin clearance is now
      recognized and implies a need to adjust dialysis dose to maintain adequate
      clearance as residual renal function declines. Reasonable, yet arbitrary, targets
      for dialysis clearances can now be asserted as Kt/V of 2.0 per week and weekly
      creatinine clearance of 60 L/wk. These current guidelines indicate a need to
      individualize dialysis dose to achieve target clearances and improved outcome.
      Current data also indicate that malnutrition is highly prevalent in the PD
      population and is associated with poor clinical outcomes, including decreased
      survival. Deterioration in nutritional status begins before the initiation of
      dialysis, and it seems that worse nutritional status at the start of dialysis is
      a strong predicator of poor outcome. These findings suggest that earlier
      initiation of dialysis, before a significant decline in nutritional status
      occurs, is warranted to maintain good nutrition and optimize outcome.

PMID- 9165653
TI  - A brief history of vascular access for hemodialysis: an unfinished story.
AB  - Progress in the development of permanent vascular access for hemodialysis has
      been much slower than progress in other areas of end-stage renal disease (ESRD)
      patient care. This article provides a brief historical overview of the major
      means used for vascular access since the start of chronic hemodialysis. These
      access modalities include external shunts, arteriovenous fistulae, prosthetic
      arteriovenous grafts, needle-less access devices, and tunneled central venous
      catheters. Despite the evolution of access methodology, vascular access
      complications remain a major impediment to the full rehabilitation of the chronic
      hemodialysis patient.

PMID- 9165654
TI  - Meaningful rehabilitation of the end-stage renal disease patient.
AB  - In this highly technological age, health care providers are called to attend to
      the patient as a whole person, with dreams and goals and a desire for purpose and
      meaning in life. In this article, we propose a broadened definition of
      rehabilitation and a rehabilitation program designed to effect an improvement in
      the quality of life of each renal patient by aiming to restore meaningful
      existence in each of their lives. An individualized plan for rehabilitation can
      be constructed and implemented with far-reaching success when the focus is on the
      life goals of the patient, whether physical, social, psychological, or
      intellectual. These programs not only enhance the quality of life of the patient
      with end-stage renal disease, but are cost-effective, both at the societal level
      and at the level of the dialysis clinic.

PMID- 9165655
TI  - Metabolic aspects of polycystic ovary syndrome.
AB  - The metabolic aberrations in patients with polycystic ovary syndrome (PCOS)
      demand a shift in clinical care from symptom driven to the prevention of chronic
      disease. The onset of carbohydrate intolerance or diabetes may be accelerated.
      The lipoprotein lipid profiles are compatible with the effects of insulin
      resistance. Disturbed cholesterol and triglyceride metabolism may eventuate in
      premature cardiovascular disease.

PMID- 9165656
TI  - Role of hyperinsulinemia in the pathogenesis of the polycystic ovary syndrome,
      and its clinical implications.
AB  - The polycystic ovary syndrome (PCOS) is a prevalent disorder affecting
      approximately 6% of women of reproductive age, and is characterized by
      anovulation and hyperandrogenism. It has also become apparent that a frequent
      feature of women with PCOS is insulin resistance accompanied by compensatory
      hyperinsulinemia, and increasing evidence suggests that hyperinsulinemia plays an
      important role in the pathogenesis of PCOS. This article will review (1) evidence
      indicating that insulin contributes to the hyperandrogenism of PCOS by
      stimulating ovarian androgen production and decreasing serum sex hormone-binding
      globulin (SHBG) concentrations; (2) possible direct effects of hyperinsulinemia
      on folliculogenesis; (3) the relationship between insulin and adrenal androgens
      in women; and (4) therapeutic and clinical implications of these findings.

PMID- 9165657
TI  - Insulin-like growth factor binding proteins: do they play a role in polycystic
      ovary syndrome?
AB  - Insulin-like growth factor (IGF) binding proteins are produced by ovarian
      follicular cells and can oppose the effects of the IGFs and gonadotropins on
      these cells. Since polycystic ovarian syndrome (PCOS) is characterized by
      disordered follicular development, with the accumulation of antral follicles
      within the ovary which fail to respond appropriately to endogenous FSH, it has
      been hypothesized that one or more IGFBPs, which can act as FSH antagonists in
      vitro, could play a role in inhibiting follicular development in this syndrome.
      Follicular fluid IGFBP levels, however, do not differ between PCOS follicles and
      the androgenic, presumably atretic follicles of cycling women without PCOS. Serum
      IGFBP-1 levels are lower in PCOS, likely because of hyperinsulinemia, and serum
      free IGF-1 levels are raised. This alternation may drive the excess thecal
      androgen production characteristic of PCOS follicles. Alterations in IGFBPs may
      sustain the anovulatory steady state in PCOS but are unlikely to initiate
      development of the syndrome.

PMID- 9165658
TI  - Adrenal involvement in polycystic ovary syndrome.
AB  - The etiology of hyperandrogenic chronic anovulation is heterogeneous and
      relatively unknown in the majority of cases. Affected individuals in this latter
      segment are considered to have polycystic ovary syndrome (PCOS) of which 50 to
      60% exhibit androgen excess of adrenal origin. An understanding of normal adrenal
      function provides insight into the factors that contribute to adrenal androgen
      excess in PCOS. Since pituitary ACTH secretion promotes developmental growth and
      overall steroidogenic efficiency within the adrenal cortex, it is probable that
      these actions of ACTH along with the adrenal's unique centripetal circulation
      play a major role in the induction of adrenarche. This latter phenomenon is
      characterized by alterations in adrenocortical morphology and steroidogenic
      enzyme activities culminating in increases in adrenal androgens to normal
      circulating adult levels. Thus, it is not surprising that adrenal dynamic testing
      has revealed increased 17,20 lyase activity or adrenal androgen hyper
      responsiveness to ACTH as the two abnormalities leading to adrenal androgen
      excess in PCOS. Whereas 17,20 lyase hyperactivity diagnosed by defined criteria
      in response to pharmacological ACTH may be an intrinsic genetic defect, increases
      in 17,20 lyase activity and adrenal androgen hyper-responsiveness to ACTH in
      response to physiological ACTH may be promoted by the functional elevation of
      estrogen of ovarian origin in PCOS. The latest in vitro data suggest the estrogen
      may elicit its effect on the adrenal cortex through a receptor mediated
      mechanism. Therefore, the currently available data indicate that adrenal androgen
      excess in PCOS is also heterogeneous in etiology.

PMID- 9165659
TI  - Pathophysiology of ovarian steroid secretion in polycystic ovary syndrome.
AB  - The ovary in polycystic ovary syndrome (PCOS) produces markedly increased amounts
      of steroids in response to gonadotropin stimulation. Because FSH secretion is
      under tight long-loop negative-feedback control and LH is not, hyperandrogenism
      is the primary clinical manifestation of excess steroid production in PCOS.
      However, estrogen production by multiple, small follicles may inhibit FSH
      secretion sufficiently to prevent selection of a single, dominant follicle.
      Ovarian stimulation testing has suggested that ovarian hyperandrogenism is a
      result of dysregulation of the androgen producing enzyme P450c17. ACTH
      stimulation testing is consistent with dysregulation of adrenal P450c17 in about
      two-thirds of hyperandrogenic women. In most cases dysregulation appears to be
      due to an intrinsic abnormality of P450c17, or to an abnormality of
      autocrine/paracrine factors which regulate P450c17. Both LH and insulin
      hypersecretion are most often a result of the steroid secretory abnormalities.
      Once present they may amplify the underlying cause of dysregulation of P450c17.

PMID- 9165660
TI  - Can polycystic ovary syndrome exist without concomitant hypothalamic dysfunction?
AB  - Polycystic ovary syndrome describes a conformational ovarian state that may be
      the final common manifestation of several pathogenic pathways. Because the
      ovarian thecal and stromal hyperplasia characteristic of polycystic ovarian (PCO)
      morphology depends upon relative LH excess while follicular arrest requires a
      relative deficiency of FSH, it is likely that the PCO morphology cannot be
      expressed or maintained without both prior and concomitant exposure to the
      characteristic alterations in hypothalamic-pituitary secretion. Although
      increased LH and decreased FSH secretion are hypothesized to be integral to the
      expression of this morphological state and, in this limited sense, causal, this
      dependence does not necessarily mean that hypothalamic alterations are the
      primary etiology of this syndrome. However, recognition of the relationship
      between gonadotropin secretory alterations and the development of the PCO state
      does have treatment implications.

PMID- 9165661
TI  - Role of growth hormone in polycystic ovarian syndrome.
AB  - Given recent in-vitro and in-vivo evidence that insulin and growth hormone may
      have gonadotropin-augmenting effects, the putative endocrine role of serum growth
      hormone levels in women with polycystic ovarian syndrome (PCOS) has been
      investigated in several studies since 1990. Obesity is a disease entity in its
      own right and, therefore, a confounding influence on investigations of PCOS. PCOS
      in the absence of obesity may be viewed as the "authentic syndrome". The use of
      IGF-1 as a marker of growth hormone secretion is not fully adequate as there is
      little to no correlation between this peptide and growth hormone in women with
      PCOS. The development of hyposomatotropinism in obese PCOS women appears to be an
      obesity-dependent event. The confirmed observation in both obese and lean women
      with and without PCOS of serum IGF-1 and IGFBP-3 levels requires further
      delineation. Preliminary evidence suggest that GH may play a role in the lean
      woman with PCOS and that the presence of obesity dampens its effect. Future
      investigations of the role of growth hormone in PCOS are dependent on first
      elucidating the role of GH in adult women and in the disease state of obesity.

PMID- 9165662
TI  - Surgical approaches to ovulation induction.
AB  - This article provides a review of published data on surgical methods of ovulation
      induction for polycystic ovary syndrome (PCOS). Areas that were discussed include
      the historical background of these procedures, their outcome as reported in the
      literature and potential adverse effects.

PMID- 9165663
TI  - Lecturing on polycystic ovary syndrome (PCOS)

PMID- 9165664
TI  - Chest trauma and its impact on the release of vasoactive mediators.
AB  - Every year, major chest injury is involved in 56% of deaths in trauma victims.
      Blunt chest trauma apparently plays a crucial role in trauma-induced death of
      multiply injured patients. Therefore, the aim of this study was to evaluate the
      impact of different types of injuries, including lung tissue damage, on the
      release of various prostanoids. In a prospective study, the release of
      arachidonic acid (AA) metabolites was estimated in patients suffering blunt chest
      trauma alone, i.e., single thoracic injury, and in multiple injured patients
      including blunt chest trauma. The results were compared with those of patients
      suffering from single long bone fractures of the leg without additional injury.
      The plasma concentrations of the AA metabolites, prostacyclin, thromboxane,
      prostaglandin F2 alpha, and prostaglandin M were determined immediately after
      admission and in hourly and daily intervals thereafter. Despite clearly different
      injury scores, elevated levels of circulating AA metabolites were found in the
      plasma in all patients. This study reveals that any trauma increases
      significantly the release of prostanoids into the peripheral blood without regard
      to the impact of tissue damage. This phenomenon is, however, most pronounced
      following lung injury. On the basis of these results we suggest that there is a
      specific impact of those mediators in blunt chest trauma. The prostanoids
      apparently are suitable to describe and even to monitor the extent of thoracic
      trauma, thus giving additional information in some respect to the individual
      outcome.

PMID- 9165665
TI  - Hyper- and hypocardiodynamic states are associated with externalization and
      internalization, respectively, of alpha-adrenergic receptors in rat heart during
      sepsis.
AB  - Alterations in the distribution of alpha-adrenergic receptors (alpha ARs) in two
      subcellular organelles, the sarcolemmal membrane and the light vesicle, of rat
      heart during the progression of sepsis were studied. Sepsis was induced by cecal
      ligation and puncture (CLP). alpha ARs were assayed by using [3H]prazosin binding
      and photoaffinity labeling with [125I]arylazidoprazosin in combination with
      polyacrylamide gel electrophoresis. Septic rat hearts exhibit two distinct
      phases: an initial hypercardiodynamic (9 h after CLP; early sepsis) followed by a
      hypocardiodynamic (18 h after CLP; late sepsis) phase. [3H]prazosin binding
      studies show that during early sepsis, the Bmax (maximal binding capacity) was
      increased by 21.4% in sarcolemma but was decreased by 22.5% in light vesicles,
      while during late sepsis, the Bmax was decreased by 25.4% in sarcolemma but was
      increased by 60.8% in light vesicles. The photoaffinity labeling studies revealed
      three binding peptides with M(r) of 77, 68, and 39 kDa. The total binding for the
      three label peptides during early sepsis was increased by 25.5% in sarcolemma but
      was decreased by 40% in light vesicles, while during late sepsis, the total
      binding was decreased by 32.1% in sarcolemma but was increased by 35.8% in light
      vesicles. These data indicate that alpha ARs in the rat heart were externalized
      from light vesicles to sarcolemma during early hypercardiodynamic phase while
      they were internalized from surface membranes to intracellular compartment during
      late hypocardiodynamic phase of sepsis. Because alpha ARs play an important role
      in regulating myocardial contractility, an initial externalization followed by
      internalization of alpha ARs may contribute to the development of the initial
      hypercardiodynamic and the subsequent hypocardiodynamic states during sepsis.

PMID- 9165666
TI  - Differential effects of acute hypoxia and endotoxin on the secretion and
      expression of bone marrow interleukin-1 and interleukin-6.
AB  - Hemorrhagic shock induces tissue hypoxia and has been demonstrated to alter the
      myelopoietic response to bacterial lipopolysaccharide (LPS). Interleukin-1 and
      interleukin-6 are important mediators of immunologic events after hemorrhagic
      shock. Bone marrow stroma release inflammatory cytokines, which may play a role
      in the regulation of myelopoiesis after injury. The aim of this study was to
      correlate cytokine gene expression with protein release and myelopoiesis by total
      bone marrow cells. The role of bone marrow stroma after exposure to hypoxia and
      lipopolysaccharide was also examined. BALB/c mice were designated as normoxia or
      hypoxia and total bone marrow cells were harvested. Hypoxia mice were exposed to
      2 h of 5% O2/95% N2, and then returned to room air. Additional groups of mice
      were given LPS intraperitoneally. Bone marrow stroma, from BALB/c mice, was
      similarly designated. Myelopoiesis was assessed by growth of granulocyte
      macrophage progenitor cells (CFU-GM). Interleukin-1 and interleukin-6 protein
      activity was assessed by bioassay. RNA was extracted from both total bone marrow
      cells and bone marrow stroma. By day 5, LPS alone resulted in a 93% increase in
      CFU-GM versus normoxia. Hypoxia and LPS exposure significantly decreased CFU-GM
      on days 1, 3, and 5. LPS alone induced an increase in interleukin-6. At 2, 6, and
      24 h, hypoxia blunted interleukin-6 release in response to LPS. Hypoxia alone
      could not induce interleukin-6. However, hypoxia did induce interleukin-1 mRNA
      without the release of bioactive protein. In the remainder of groups, interleukin
      1 protein levels and mRNA levels were correlated. Bone marrow stroma interleukin
      1 and interleukin-6 protein activity was consistently correlated with that of
      total bone marrow. These data demonstrate that bone marrow cytokine production is
      differentially regulated by hypoxia. Hypoxia impairs interleukin-6 protein and
      mRNA in response to LPS, which may play a role in the suppression of myelopoiesis
      after shock. Also, bone marrow stroma plays an integral role in regulating
      myelopoiesis.

PMID- 9165667
TI  - Induction of muscle glutamine synthetase gene expression during endotoxemia is
      adrenal gland dependent.
AB  - Skeletal muscle plays a crucial role in maintaining nitrogen homeostasis during
      health and critical illness by exporting glutamine, the most abundant amino acid
      in the blood. We hypothesized that induction of glutamine synthetase (GS)
      expression, the principal enzyme of de novo glutamine biosynthesis, in skeletal
      muscle after endotoxin administration was adrenal gland dependent. We studied the
      expression of GS in normal and adrenalectomized rats after intraperitoneal
      administration of Escherichia coli lipopolysaccharide (LPS). Treatment of normal
      rats with LPS resulted in a marked increase in GS mRNA that was dose and time
      dependent, and preceded the increase in GS protein and specific activity. The
      increase in muscle GS mRNA observed in normal rats in response to LPS was
      abrogated in adrenalectomized rats at 3 h after high dose LPS treatment and
      markedly attenuated at 5.5 h after low dose LPS treatment. These and other
      studies implicate glucocorticoid hormones as a key, but not exclusive, regulator
      of skeletal muscle GS expression after a catabolic insult.

PMID- 9165668
TI  - Studies on polymorphonuclear leukocyte bactericidal function: II. The role of
      oxidative stress.
AB  - We have previously detailed the effects of exogenous cytokines (IL-1 beta, TNF
      alpha, and IL-8) on polymorphonuclear leukocyte (PMN) bactericidal function
      during normoxia. In these studies, we have investigated the effects of hypoxia +/
      reoxygenation independently and with IL-1 beta, TNF-alpha, and IL-8 on PMN
      bactericidal activity. Hypoxia in and of itself did not significantly alter PMN
      bactericidal activity against Escherichia coli or Staphylcoccus aureus; however,
      after 2 h of reoxygenation (H/R), PMN bactericidal activity against E. coli was
      significantly reduced compared with levels seen after 2 h of hypoxia. Similar to
      what was observed during normoxia, TNF-alpha, IL-1 beta, and IL-8 increased PMN
      bactericidal activity during hypoxia compared with buffer control PMN for S.
      aureus but not E. coli after 4 h of hypoxia. Following H/R, neither TNF-alpha, IL
      1 beta, nor IL-8 reversed the decline in bactericidal activity induced by
      reoxygenation alone. Monoclonal antibodies that blocked the functional epitope of
      particular cytokine receptors demonstrated that during both hypoxia and H/R IL-1
      beta R type I, IL-8R type A, and TNF-alpha R p60 were the predominant receptors
      responsible for mediating the bactericidal effect of the cytokines. During
      hypoxia and H/R, the addition of exogenous cytokines did prevent the fall in
      bactericidal activity seen as PMN: target ratios decreased. The decline in
      bactericidal activity following H/R was mediated in part by reduced phagocytosis
      of serum-opsonized bacteria following H/R. These results demonstrated that
      oxidative stress in the form of hypoxia +/- reoxygenation independently modulate
      the effect of exogenously added cytokines on PMN bactericidal capability.

PMID- 9165669
TI  - Differential effects of hyperoxia on the inducible and constitutive isoforms of
      nitric oxide synthase in the lung.
AB  - Hyperoxia is commonly used in the treatment of newborn respiratory distress.
      Although essential and life saving, oxygen therapy can result in the development
      of lung injury. Oxygen toxicity is associated with the production of reactive
      oxidant species. Nitric oxide (NO) is an oxidant formed by the catalysis of L
      arginine when acted upon by the enzyme nitric oxide synthase (NOS). We studied
      the differential effects of prolonged normobaric hyperoxia (FIO2 = .95, for 3, 4,
      and 5 days) on the two major NOS enzymes, constitutive endothelial cell NOS
      (ecNOS) and inducible NOS (iNOS). Hyperoxia led to a significant lung injury, as
      measured by pulmonary compliance studies. Hyperoxia did not increase serum NO
      production, measured as the concentration of nitrite and nitrate. However,
      hyperoxia did result in a small but significant increase in NO production in the
      bronchoalveolar lavage fluid, as measured by the products of nitrite and nitrate
      concentration. This increase in NO was not associated with an induction of whole
      lung iNOS, as measured by the conversion of L-[3H]arginine to L-[3H]citrulline or
      by Northern blot analysis. Hyperoxia significantly decreased ecNOS activity as
      measured by the conversion of L-[3H]arginine to L-[3H]citrulline. In addition,
      administration of the NOS inhibitor NG-nitro-L-arginine methyl ester worsened the
      injury, as measured by lung compliance and survival. Further studies need to be
      performed to determine whether this decrease in ecNOS activity during hyperoxia
      plays a role in the pathogenesis of hyperoxia-related lung injury.

PMID- 9165670
TI  - Role of nitric oxide in a nonseptic shock model induced by zymosan in the rat.
AB  - Nitric oxide (NO) is a short-lived mediator, the synthesis of which is induced by
      various cytokines during inflammatory processes. Recently, it has been proposed
      that zymosan, a nonbacterial agent, causes inflammation by inducing the
      production of various cytokines and proinflammatory mediators. In the present
      study we investigated the role of NO in a nonseptic shock model induced by
      zymosan administration in the rat. Administration of zymosan (500 mg/kg,
      intraperitoneally) in the rat induced acute peritonitis, as assessed by a marked
      increase in the leukocytes count in the exudate, as well as by an increase in the
      exudate nitrate/nitrite concentration. Zymosan-treated rats developed a severe
      hypotension and showed signs of systemic illness, significant loss of body
      weight, and a high mortality rate (53% of animals died within 72 h). Elevated
      plasma levels of nitrite and nitrate were also observed in zymosan-treated rats
      compared with control rats (67 +/- 4 microM and 23 +/- 2 microM, respectively; p
      < .01). In ex vivo experiments, vascular reactivity was studied in thoracic aorta
      rings of zymosan-treated rats. The contractile responses to norepinephrine (100
      nM) and endothelin-1 (5 nM) were significantly reduced. An impairment of the
      endothelial-dependent relaxation in response to acetylcholine was also observed.
      Pretreatment of zymosan-shocked rats with NG-nitro-L-arginine methyl ester (L
      NAME) or NG-monomethyl-L-arginine (L-NMA), (10 mg/kg, subcutaneously, 15 min
      before zymosan) decreased mortality, prevented the development of peritonitis,
      improved ex vivo vascular reactivity, and significantly reduced hypotension. Our
      data suggest that overproduction of NO plays a role in the zymosan-induced
      peritonitis and cardiovascular derangements in the rats.

PMID- 9165671
TI  - The influence of heat shock protein 70 induction on hemodynamic variables in a
      porcine model of recurrent endotoxemia.
AB  - The manipulation of stress gene expression by heavy metals provides protection
      against the lethal effects of endotoxemia in murine models of septic shock. These
      findings suggest that the increased resistance to endotoxin in vivo after stress
      protein induction could be explained by an attenuation of hemodynamic alterations
      and an altered pattern of inflammatory mediator release. Therefore, we measured
      main hemodynamic variables such as systemic and pulmonary artery pressure,
      cardiac output, heart rate, central venous pressure, and pulmonary artery wedge
      pressure, as well as the time-course of thromboxane-B2, 6-keto-PGF1 alpha, and
      interleukin 6 formation with and without induction of the stress response in an
      established porcine model of recurrent endotoxemia (Circ Shock 35:237-244, 1991).
      Induction of the stress response was carried out by a pretreatment with Zn2+ (25
      mg/kg zinc-bis-(DL-hydrogenaspartate) = 5 mg/kg Zn2+). Pretreatment with Zn2+
      prior to lipopolysaccharide (LPS) infusion induced an increased heat shock
      protein 70 (HSP70) expression in the lungs, liver, and kidneys and significantly
      increased plasma levels of interleukin 6, 6-keto-PGF1 alpha, and thromboxane-B2,
      compared with untreated controls. After LPS infusion, however, pretreated animals
      showed significantly decreased peak plasma levels of all mediators compared with
      the untreated group. Hemodynamic data presented significantly decreased peak
      pulmonary artery pressure and pulmonary vascular resistance index values,
      significantly increased systemic artery pressure and systemic vascular resistance
      index values, and significantly altered hypodynamic/hyperdynamic cardiac output
      levels in the pretreated group. In conclusion, the data show that the induction
      of HSP70 by Zn2+ attenuates the liberation of inflammatory mediators, as well as
      the course of hemodynamic variables due to LPS.

PMID- 9165672
TI  - Cardiopulmonary dysfunction during porcine endotoxin shock is effectively
      counteracted by the endothelin receptor antagonist bosentan.
AB  - In a porcine endotoxin shock model, the mixed nonpeptide endothelin receptor
      antagonist bosentan was administered 2 h after onset of endotoxemia (n = 8).
      Cardiopulmonary vascular changes, oxygen-related variables, and plasma levels of
      endothelin-1-like immunoreactivity were compared with a control group that
      received only endotoxin (n = 8). Bosentan abolished the progressive increase in
      mean pulmonary artery pressure and pulmonary vascular resistance seen in
      controls. Possible mechanisms include blockade of vasoconstrictive endothelin
      receptors, and a lesser degree of edema and inflammation indicated by less
      alveolar protein and a lower inflammatory cell count observed in bronchoalveolar
      lavage. Further, bosentan restored cardiac index to the pre-endotoxin level by an
      increase in stroke volume index, improved systemic oxygen delivery, and acid base
      balance. Because mean arterial blood pressure was unaffected, bosentan reduced
      systemic vascular resistance. Endotoxemia resulted in an increase in tumor
      necrosis factor-alpha and endothelin-1-like immunoreactivity plasma levels, the
      latter being further increased by bosentan. In conclusion, in porcine
      endotoxemia, treatment with the endothelin receptor antagonist bosentan,
      administered during fulminate shock, abolished pulmonary hypertension and
      restored cardiac index. These findings suggest that bosentan could be an
      effective treatment for reversing a deteriorated cardiopulmonary state during
      septic shock.

PMID- 9165673
TI  - Amrinone and theophylline differentially regulate cytokine and nitric oxide
      production in endotoxemic mice.
AB  - Intracellular cyclic nucleotide levels play an important role in the regulation
      of several immunological processes. Since elevation of intracellular cyclic
      adenosine monophosphate and/or cyclic guanosine monophosphate concentration by
      inhibition of phosphodiesterase (PDE) is known to modulate the inflammatory
      response, we compared the effect of amrinone, an inhibitor of the PDE III
      isoenzyme, and of theophylline, a nonspecific PDE inhibitor, on the plasma tumor
      necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-10 (IL-10),
      and nitric oxide response in mice to intraperitoneal injection of bacterial
      lipopolysaccharide (LPS). Intraperitoneal treatment of animals with amrinone (100
      mg/kg) 30 min before LPS administration decreased both plasma IL-6 and IL-10
      concentrations in the first phase of the response, but enhanced plasma levels of
      these cytokines in the second part. In contrast, pretreatment of the animals with
      theophylline (100 mg/kg) enhanced LPS-induced plasma IL-6 and IL-10 levels during
      the whole response. However, pretreatment with both PDE inhibitors resulted in a
      marked inhibition of LPS-evoked plasma concentrations of TNF-alpha and
      nitrite/nitrate (breakdown products of nitric oxide) throughout the response.
      This study demonstrates for the first time that amrinone and theophylline possess
      differential, but primarily anti-inflammatory, properties during LPS-induced
      systemic inflammation in the mouse.

PMID- 9165674
TI  - Possible relationship between histamine and nitric oxide release in the
      postischemic flow response following mesenteric ischemia of different durations.
AB  - During the postischemic flow response (PFR), vasodilator mediators such as nitric
      oxide (NO) and histamine are liberated, influencing the blood flow rate at the
      onset of reperfusion. The possible roles of these two mediators, and the
      relationship between their release, were examined during segmental intestinal
      ischemia of different durations and subsequent reperfusion in two series of
      anesthetized dogs. In series I (untreated ischemia), 15, 30, 60, and 120 min
      ischemia and 2 h reperfusion were studied. In series II, the same experimental
      protocol was repeated after pretreatment with the NO synthase inhibitor N-nitro-L
      arginine (NNA, 10 mumol/kg, i.e., 2.19 mg/kg). Intramucosal pH (pHi), segmental
      blood flow and effluent histamine levels were measured, and segmental vascular
      resistance (SVR) and PFR volumes were calculated. The ischemic periods caused a
      considerable fall in pHi. Reperfusion resulted in an early return to normal pHi
      levels following a 15 or 30 min ischemia, but this process took longer after
      longer occlusions. In the later phase of reperfusion, SVR was elevated. The PFR
      volume increased in proportion to the duration of occlusion, except after the 120
      min ischemia. At the onset of reperfusion, peak histamine levels rose in parallel
      with the duration of ischemia. During reperfusion, a prolonged decrease in pHi,
      an increase in SVR, and a reduction in PFR volume, with no significant histamine
      level elevation, were observed in the NNA-treated groups. This study indicates
      that both NO and histamine take part in the PFR in the canine small intestine.
      Inhibition of NO synthesis prevents the postischemic release of histamine.

PMID- 9165675
TI  - Cytosolic Ca2+ concentration and contraction-relaxation properties of ventricular
      myocytes from Escherichia coli endotoxemic guinea pigs: effect of fluid
      resuscitation.
AB  - Hearts isolated from a guinea pig model of Escherichia coli endotoxemia exhibit
      decreased systolic contractile function and reduced diastolic compliance of the
      left ventricle within 4 h after injection of endotoxin. Fluid resuscitation
      prevented the endotoxin-induced decrease in diastolic compliance without
      affecting systolic contractile depression. Because intrinsic myocardial
      dysfunction after endotoxemia may result from alterations in intracellular Ca2+
      handling, we tested the hypothesis that in vivo fluid resuscitation improved
      diastolic function by altering Ca2+ handling of the myocardium. We tested this
      hypothesis by measuring cell shortening and intracellular Ca2+ of ventricular
      myocytes isolated from endotoxemic guinea pigs. E. coli endotoxin (LPS, 1 mg/kg)
      injected guinea pigs were divided into resuscitated and nonresuscitated groups.
      Fluid resuscitated animals received a Ringer's infusion (8 mL.kg-1.h-1)
      intravenously (i.v.) beginning immediately after endotoxin injection. Four hours
      later, ventricular myocytes were isolated enzymatically and loaded with fura
      2/AM. When myocytes were field stimulated at .8 Hz, peak systolic Ca2+ transients
      of LPS-resuscitated (619 +/- 75 nM) and LPS-nonresuscitated (599 +/- 60 nM)
      myocytes were not significantly different from each other, but both were
      significantly less than values from control myocytes (1187 +/- 118 nM, p < .05).
      The percentage of cell shortening of LPS-resuscitated (6.2 +/- .9%) and LPS
      nonresuscitated (6.2 +/- .3%) myocytes were also less than control (11.8 +/- .5%,
      p < .05). In contrast to improved diastolic compliance of fluid-resuscitated
      hearts, diastolic [Ca2+]i of myocytes (at .8 Hz) from LPS-resuscitated animals
      (138 +/- 47 nM) was not statistically different from LPS-nonresuscitated animals
      (129 +/- 19 nM). Diastolic values of both LPS groups were consistently lower than
      control value (251 +/- 38 nM, p < .05). These data suggest that improved
      diastolic compliance of LPS hearts following fluid resuscitation is not
      associated with improved myocyte contractility or myoplasmic Ca2+ handling.

PMID- 9165676
TI  - Postmortem perinatal examination: the role of magnetic resonance imaging.

PMID- 9165677
TI  - Cardiotocography versus Doppler.

PMID- 9165678
TI  - Cardiotocogram compared to Doppler investigation of the fetal circulation in the
      premature growth-retarded fetus: longitudinal observations.
AB  - It was our objective to compare computerized fetal heart rate analysis with blood
      flow velocity waveform analysis of the arterial and venous fetal circulation in
      intrauterine growth retardation. We report five illustrative cases with
      longitudinal observations of fetal Doppler findings and fetal heart rate between
      23 and 32 weeks of gestation. Blood flow waveforms were recorded from the
      umbilical artery, middle cerebral artery, descending aorta, ductus venosus and
      inferior vena cava. Fetal heart rate was analyzed by a computer system according
      to the Dawes-Redman criteria. The time sequence of deterioration is described
      individually for each fetus. An abrupt increase in pulsatility of ductus venosus
      waveforms with loss of forward flow velocity during atrial contraction preceded
      abnormally low short-term variation of fetal heart rate. With advanced
      gestational age and concomitant maternal disease, we observed severe alterations
      of flow velocity waveforms within 12 h of normal Doppler measurements, which is
      in contrast to findings in the second trimester, in which severely abnormal
      venous waveforms were observed over a period of several weeks before intrauterine
      death occurred. In a fetus with terminally low short-term variation, normal
      venous waveforms indicated fetal well-being despite an abnormal cardiotocogram
      (CTG). We challenge the current concept that the CTG is the best available
      parameter to determine the optimal time for elective delivery of premature growth
      retarded fetuses. Deterioration in ductus venosus blood flow seems to precede an
      abnormal CTG and thus heralds the need for delivery.

PMID- 9165679
TI  - Demonstration of fetal coronary blood flow by Doppler ultrasound in relation to
      arterial and venous flow velocity waveforms and perinatal outcome--the 'heart
      sparing effect'.
AB  - This longitudinal observational study evaluates the stage at which coronary flow
      can be visualized by color-coded and pulsed wave Doppler sonography in fetuses
      with normal cardiac anatomy. Fetal biometry, echocardiography and Doppler
      examination of the umbilical and middle cerebral arteries, ductus venosus,
      inferior vena cava and umbilical vein were performed in 109 cases. Fetuses were
      divided into five groups based on the Doppler examination of the umbilical
      artery, birth weight and the ability to visualize coronary blood flow. Coronary
      blood flow was identified in six of 55 fetuses with normal growth who had normal
      Doppler studies and perinatal outcome. In these, visualization of coronary blood
      flow was possible after 31 weeks' gestation at a median gestational age of 37
      weeks. Coronary blood flow was also visualized in ten of 54 fetuses with severe
      intrauterine growth retardation and highly pathological flow velocity waveforms
      in all vessels soon after a significant increase of venous indices in the
      inferior vena cava and ductus venosus. In these cases, coronary blood flow was
      identified at a significantly earlier gestational age (median 27 weeks). These
      fetuses had a poor perinatal outcome (average birth weight less than 3rd centile,
      mortality rate 50%, significantly lower umbilical artery blood pH and Apgar
      scores after 1 and 5 min). Intrauterine fetal death occurred in five fetuses
      after a median of 3.5 days following visualization of coronary blood flow. Median
      coronary peak blood flow velocities in the right coronary artery were higher in
      intrauterine growth-retarded than appropriate-for-gestational-age fetuses.

PMID- 9165680
TI  - Three-vessel view of the fetal upper mediastinum: an easy means of detecting
      abnormalities of the ventricular outflow tracts and great arteries during
      obstetric screening.
AB  - The three-vessel view is a transverse view of the fetal upper mediastinum is as
      simple to obtain as the four-chamber view. It demonstrates the main pulmonary
      artery, ascending aorta and superior vena cava in cross- or oblique sections. The
      purposes of this study were to describe the normal anatomy of the three-vessel
      view and to analyze what anatomical changes would occur in this view when there
      are lesions of the ventricular outflow tracts and/or great arteries. Sonograms of
      29 fetuses with lesions involving the ventricular outflow tracts and/or great
      arteries were reviewed. Three-vessel views were evaluated in terms of vessel
      size, number, arrangement and alignment. Twenty-eight of 29 fetuses showed an
      abnormal three-vessel view that included abnormal vessel size (n = 12), abnormal
      alignment (n = 8), abnormal arrangement (n = 7) and abnormal vessel number (n =
      3). The vessel size was abnormal in obstructive lesions of the right (n = 4) or
      the left (n = 8) side of the heart. An abnormal alignment was seen in tetralogy
      of Fallot (n = 6) and double-outlet right ventricle (n = 2) that showed anterior
      displacement of the aorta. An abnormal arrangement was seen in complete (n = 4)
      and corrected (n = 1) transposition, double-outlet right ventricle (n = 1) and
      pulmonary atresia with ventricular septal defect (n = 1). Only two vessels were
      seen in truncus arteriosus (n = 1). Four vessels were seen in persistent left
      superior vena cava (n = 2). A fetus with pulmonary atresia and intact ventricular
      septum showed a normal three-vessel view. In conclusion, most of the lesions
      involving the ventricular outflow tracts and/or great arteries showed an abnormal
      three-vessel view.

PMID- 9165681
TI  - Premature contractions: possible influence of sonographic measurement of cervical
      length on clinical management.
AB  - In a retrospective case control study with historical controls, the influence of
      the introduction of vaginal sonographic cervical length measurement on the
      utilization of hospital services and pregnancy outcome of gravid women at risk of
      preterm delivery was examined. Prior to the introduction of vaginal
      ultrasonography to measure cervical length, we registered 76 hospitalizations
      totalling 1827 hospitalization days due to premature cervical ripening and/or
      premature labor in 1991 and 1992. In 1994 and 1995, after vaginal ultrasonography
      was introduced and intravenous tocolysis was limited to cases with cervical
      shortening to less than 3 cm, there were 64 admissions resulting in just 869
      hospitalization days. Long-term hospitalizations (over 10 days) were reduced from
      55 to 25 cases (p < 0.0001) and the median length of hospital stay decreased from
      18 to 8 days (p < 0.0001). The number of preterm births (< or = 37 weeks)
      remained stable: 12 cases in 1991-1992 and 13 cases in 1994-1995. In conclusion,
      vaginal sonographic measurement of cervical length provides an objective
      criterion for cervical shortening with premature labor. The method could
      therefore be a suitable means of reducing unnecessary therapeutic interventions
      in gravid women with premature contractions and/or cervical dilatation. A
      prospective randomized trial to confirm these findings is suggested.

PMID- 9165682
TI  - Measurement of the pregnant cervix by transvaginal sonography: an interobserver
      study and new standards to improve the interobserver variability.
AB  - Transvaginal sonography has become an important tool for assessing the gravid
      cervix uteri, especially in patients at risk for cervical incompetence and
      preterm delivery. The purpose of our prospective study was to evaluate
      interobserver variability in measurements of the cervical length and, as a second
      step, improve the reproducibility and interobserver discrepancy by the
      introduction of quality control standards when producing and measuring the image
      of the cervix. Before the introduction of these standards we obtained 46
      measurements and observed a mean cervical length (internal to external os) of
      33.7 mm (range 26-52 mm) and an interobserver average discrepancy of 3.04 mm
      (range 0-6 mm). Later, measurements were obtained only when the following
      conditions were assured and visualized on the screen: (1) the internal os is
      either flat or is an isosceles triangle; (2) the whole length of the cervical
      canal can be observed; (3) a symmetric image of the external os can be obtained;
      and (4) the distance from the surface of the posterior lip to the cervical canal
      is equal to the distance from the anterior lip to the cervical canal. After the
      implementation of these quality control standards, 70 measurements were performed
      obtaining a mean length of 35.3 mm (range 27-51) and an average interobserver
      discrepancy of 1.24 mm (range 0-4). Thus the measurement error was significantly
      lower following introduction of quality control standards. Furthermore, the
      coefficient of variation dropped from 7.1% to 3.3% after the introduction of the
      guidelines. We believe that these guidelines could be helpful by making the
      measurements of the cervical length more accurate, reducing the interobserver
      variability, improving the reproducibility and promoting the role of transvaginal
      sonography in monitoring the incompetent cervix.

PMID- 9165683
TI  - Prenatal diagnosis of ventriculo-coronary communications in a second-trimester
      fetus using transvaginal and transabdominal color Doppler sonography.
AB  - We report on the prenatal diagnosis of ventriculo-coronary communication
      associated with pulmonary atresia and an intact interventricular septum. The
      diagnosis was made by transvaginal color Doppler sonography at 17 weeks'
      gestation and confirmed by transabdominal sonography at 19 weeks. Color Doppler
      demonstrated the communication between the distal hypoplastic right ventricle and
      the right coronary artery, with the course of this vessel situated along the
      outer heart wall. Spectral Doppler assessment showed bidirectional arterial flow
      in this vessel. Extracardiac skeletal anomalies (cleft hands and feet) were also
      detected and classified as an ectrodactyly-ectodermal dysplasia clefting (EEC)
      syndrome. This led the parents to opt for termination of pregnancy. All findings
      were confirmed on autopsy. Using stereomicroscopy the malformations of the
      coronary system and main connections to the lumen of the right ventricle were
      additionally demonstrated. To our knowledge this is the first report on the
      identification of coronary artery malformations in a midtrimester fetus using
      transvaginal color Doppler. The early appearance enabled us to investigate the
      pathophysiological sequence of the combined defect. Further investigation might
      elucidate whether ventriculo-coronary communications arise secondary to pulmonary
      atresia and intact inter-ventricular septum, due to increased ventricular
      pressure, or are the primary defect leading to intrauterine pulmonary atresia or,
      indeed, whether both defects appear simultaneously.

PMID- 9165684
TI  - Round ligament varices in pregnancy mimicking inguinal hernia: an ultrasound
      diagnosis.
AB  - A case of uncomplicated round ligament varices mimicking an irreducible inguinal
      hernia in the third trimester of pregnancy is presented. The clinical and
      ultrasound features, pathophysiology and the role of conservative management are
      discussed. Non-surgical treatment led to spontaneous regression after delivery.

PMID- 9165685
TI  - Giant glioependymal cyst resembling holoprosencephaly on prenatal ultrasound:
      case report and review of the literature.
AB  - We report the earliest in utero presentation of a 'giant' glioependymal cyst
      detected on routine prenatal ultrasound at 22 weeks estimated gestational age.
      The clinicopathologic features of these rare lesions are reviewed as well as
      previous reports of glioependymal cysts detected in utero. The effects of large
      intracranial cysts on neurodevelopment are discussed as well as the differential
      diagnosis of infantile intracranial cysts and therapeutic alternatives.

PMID- 9165686
TI  - Cessation of fetal supraventricular tachycardia after compression of the
      umbilical cord.

PMID- 9165687
TI  - Presentation of the Ian Donald Gold Medal to Juriy Wladimiroff.

PMID- 9165688
TI  - Presentation of the Ian Donald Medal for Technical Development to Tom Brown.

PMID- 9165689
TI  - Interaction of proton pump inhibitors with cytochromes P450: consequences for
      drug interactions.
AB  - Omeprazole, lansoprazole and pantoprazole are metabolized by several human
      cytochromes P450, most prominently by CYP2C19 and CYP3A4. Only pantoprazole is
      also metabolized by a sulfotransferase. Differences in the quantitative
      contribution of these enzymes and in the relative affinities of the substrates
      explain some of the observed interactions with carbamazepin, diazepam, phenytoin
      and theophylline and of the impact of the CYP2C19 (mephenytoin) genetic
      polymorphism. Of these drugs, pantoprazole has the lowest potential for
      interactions, both in vitro and in human volunteer studies.

PMID- 9165690
TI  - Duodenal ulcer and gastroesophageal reflux disease today: long-term therapy--a
      sideways glance.
AB  - Acid-peptic disease is widely considered conquered or controlled, future advances
      being refinements of existing treatments rather than radical new developments.
      Yet controversies remain and developments have yet to be made. DUODENAL ULCER:
      Daily maintenance treatment with the anti-secretory drugs, histamine H2 receptor
      antagonists and proton pump blockers, controls duodenal ulcer effectively,
      markedly reducing relapse rate at one year after treatment from about 75 percent
      to 15 to 20 percent (and to about 10 percent on proton pump blockers). In
      contrast, Helicobacter pylori eradication with a one to two week course of
      treatment yields prolonged remission or cure. The consequent reduction in drug
      costs in individual patients, however, has been exceeded by increasing community
      use on the more expensive proton pump blockers for the treatment of
      gastroesophageal reflux disease. The marked decline in elective surgery since the
      introduction of histamine H2 receptor antagonists is commonly attributed to the
      power of these drugs. The fall, however, had started much earlier, indicating
      that the decline is due to changing natural history. In contrast, complication
      rates remain unaltered. An increasing proportion of newly diagnosed duodenal
      ulcer patients are elderly, and more of them now present for the first time with
      complications (in this center, about 40 percent), which consequently cannot be
      forestalled. Thus, duodenal ulcer disease is likely to remain a problem and in
      many will be a serious illness. GASTROESOPHAGEAL REFLUX DISEASE: The proton pump
      blockers have revolutionized the treatment of gastroesophageal reflux disease. In
      clinical trials they have proven markedly superior to the histamine H2 receptor
      antagonists in healing (at eight weeks, 80 to 90 percent vs. 50 to 60 percent),
      symptom relief, prevention of relapse on maintenance therapy and cost
      effectiveness. However, several issues remain. The prevalence of gastroesophageal
      reflux disease seems to be rising and is now probably the commonest acid-peptic
      disease encountered in the West. Most clinical trials comparing proton pump
      blockers vs. histamine H2 receptor antagonists have been done in patients with
      erosive esophagitis, whereas the majority (50 to 60 percent) of patients with
      gastroesophageal reflux disease have milder, generally non-erosive, disease. The
      therapeutic gain of proton pump blockers diminishes in mild disease so may not be
      worth the higher drug costs. This is an important area for investigation. The
      majority of patients with erosive esophagitis relapse when treatment is stopped
      (about 75 percent at one year). Relapse is markedly reduced (to 20 to 25 percent)
      by daily maintenance treatment with proton pump blockers. Mild disease relapses
      less often, so longterm therapy by intermittent treatment may prove acceptable
      and more cost-effective than maintenance treatment. This strategy remains
      unexplored in trials. The ideal profile of an anti-secretory drug for
      intermittent treatment would combine rapid onset of action (similar to histamine
      H2 receptor antagonists) with powerful effect (as with proton pump blockers). The
      new class of drug, the reversible proton pump blocker (e.g., BY841) approaches
      this requirement.

PMID- 9165692
TI  - Current status of acid pump antagonists (reversible PPIs).
AB  - The introduction of H2-receptor antagonists in the mid-1970s provided, for the
      first time, acceptable medical therapy for acid-related diseases. Their short
      duration of action and single receptor targeting, however, limited satisfactory
      treatment of patients. Today the control of gastric acid secretion can be
      effectively achieved by direct inhibition of the H+, K(+)-ATPase. Inhibition of
      the proton pump suppresses acid secretion independent of the route of
      stimulation. Two classes of drugs are able to inhibit the proton pump. First, the
      substituted benzimidazoles (proton pump inhibitors [PPIs]), which, due to their
      pKa of about 4, accumulate in the acidic secretory canaliculus of the stimulated
      parietal cell. Following conversion to a cationic sulfenamide, they react with
      cysteines on the extracytoplasmatic face of the H+, K(+)-ATPase subunit. Second,
      acid pump antagonists (APAs) acting by K(+)-competitive and reversible binding to
      the gastric proton pump, which is the final step for activation of acid secretion
      in the parietal cell. One possible class of APAs are imidazopyridines. BY841 was
      selected from this class and is chemically a (8-(2-methoxycarbonylamino-6-methyl
      phenylmethylamino )-2,3-dimethyl-imidazo [1,2-a]-pyridine). In pharmacological
      experiments such as pH-metry in the conscious, pentagastrin-stimulated fistula
      dog, BY841 proved to be superior to both ranitidine and omeprazole by rapidly
      elevating intragastric pH up to a value of 6. The duration of this pH elevation
      in the dog was dose-dependent. As was predicted by the above-mentioned dog model,
      available clinical phase I data confirm dose-dependent pharmacodynamics of BY841
      in man. Using both acid output and continuous 24-hr pH measurements, a pronounced
      antisecretory effect of BY841 has been found. Actually, a single 50 mg oral dose
      of BY841 immediately elevated intragastric pH to about 6. Higher doses caused a
      dose-dependent increase in duration of the pH-elevation, without any further
      increase in maximum pH values. Twice daily administration was more effective than
      once a day administration of the same daily dose. With both regimens, the
      duration of the pH-elevating effect of BY841 further increased upon repeated
      daily administration. This demonstrates lack of tolerance development, the latter
      being a well-known disadvantage of H2-receptor antagonists. In comparison with
      the standard dose of omeprazole, BY841 administered at a dose of 50 mg or 100 mg
      twice daily is markedly more effective on Day one of treatment, and both doses
      are at least as potent as omeprazole following repeated daily administration.

PMID- 9165691
TI  - Optimizing the intragastric pH as a supportive therapy in upper GI bleeding.
AB  - Acid inhibitory therapy has long been considered of no benefit for upper GI
      bleeding. The reason was that achlorhydria in the stomach could not be achieved
      with any single or combination of acid inhibitory drugs. The introduction of
      proton pump inhibitors has, for the first time, allowed the physician to
      temporarily achieve achlorhydria by large doses of intravenously applied proton
      pump inhibitors. The first placebo-controlled clinical trials have shown that,
      indeed, an intragastric pH of near 7 can significantly improve the clinical
      outcome of upper GI bleeding. Pharmacokinetic studies with proton pump inhibitors
      have shown that a bolus of 80 mg pantoprazole or omeprazole followed by immediate
      continuous infusion of eight mg per hour will result in an intragastric pH of 7
      within 20 minutes. This intragastric pH optimizes the different steps of
      hemostasis in the stomach.

PMID- 9165694
TI  - Helicobacter pylori: controversial and unsolved issues.

PMID- 9165693
TI  - CCKB/gastrin receptor antagonists: recent advances and potential uses in gastric
      secretory disorders.
AB  - Cholecystokinin (CCK) and the structurally related peptide, gastrin, have
      numerous effects on tissues in the central nervous system and gastrointestinal
      tract. Recent studies show these effect are mediated by a CCKA and CCKB receptor.
      Knowledge of the physiological role and role of CCKB receptors in pathologic
      processes has been particularly limited by the availability of selective, potent
      receptor antagonists. Recently, new members of five different classes of non
      peptide CCKB receptor antagonists are reported and are reviewed briefly. these
      include compounds isolated from Streptomyces (tetronothiodin, virginiamycin
      analogues), ureido-acetamide analogues (RP 69758, RP 72540, RP 73870), newer
      benzodiazepine analogues (L-368,935, L-740,093, YM022), pyrazolidimine analogues
      (LY 262,691) and glutamic acid analogues (CR2194). Many of these compounds have
      greater than 1000-fold selectivity for the CCKB over the CCKA receptor and some
      have greater than 10,000-fold selectivity. The pharmacology and effects of CCKB
      receptor antagonists on gastric acid secretion is briefly reviewed. Furthermore,
      the possible clinical usefulness of CCKB receptor antagonists in treating
      disorders of gastric acid secretion, in inhibiting the trophic effects of gastrin
      and in other clinical conditions is briefly discussed.

PMID- 9165695
TI  - Therapy and prevention of gastric ulcer.
AB  - After establishing the benign nature of a gastric ulcer, the treatment is
      primarily medical. This medical therapy is aimed to alleviate symptoms, to heal
      the ulcer and to prevent relapses. Based on the history of non-steroidal anti
      inflammatory drugs (NSAIDs) and the Helicobacter pylori-status, gastric ulcer
      patients can be divided into four categories (1) H. pylori positive plus NSAID
      use, (2) H. pylori positive without NSAID use, (3) NSAID use with negative H.
      pylori-status, (4) Negative H. pylori-status and no NSAID use. Patients taking
      NSAIDs should stop this therapy if possible. Patients with gastric H. pylori
      infection should be treated by a regimen of a proton pump inhibitor with at least
      two appropriate antibiotics. This treatment will result in early alleviation of
      symptoms, rapid healing of the ulcer and prophylaxis of ulcer relapse. In
      patients with gastric ulcer who cannot stop NSAIDs, maintenance therapy with
      prostaglandins or potent antisecretory drugs should be considered. The few
      patients with gastric ulcer who do not take NSAIDs and do not have gastric H.
      pylori infection should be treated by antisecretory drugs, and they should be
      carefully followed endoscopically to exclude malignant (carcinoma, lymphoma) or
      non-peptic (Crohn's disease) disease. All patients with gastric ulcer should be
      re-endoscoped to verify complete ulcer healing. Surgery may be considered in
      gastric ulcer patients with complications, in those with severe dysplasia of the
      gastric mucosa, and in those who are not able or willing to take the medication.

PMID- 9165696
TI  - Management of refractory and complicated reflux esophagitis.
AB  - Simple intermittent heartburn with minor or no esophagitis can be treated with
      simple measures including lifestyle changes and antacids as needed, or H2
      receptor antagonists (H2RA), and has a good outcome. Problematic reflux includes
      resistance to therapy, stricture, Barrett's esophagus and aspiration. Severe
      reflux esophagitis, often resistant to H2RA therapy, requires more potent
      treatment with potent acid suppression using proton pump inhibitors, often
      indefinitely. When complicated by stricture, dilatations with potent acid
      suppression are needed. Barrett's esophagus is subject to esophagitis, which is
      no more difficult to treat than other cases of esophagitis. Reflux in Barrett's
      esophagus should be treated on its own merits without regard to the presence of
      Barrett's epithelium. Dysplasia leading to adenocarcinoma is a different problem,
      apparently not influenced by reduced exposure to acid. Indications for antireflux
      surgery are quite limited and should be carefully analyzed as a cost/risk/benefit
      problem.

PMID- 9165697
TI  - Laparoscopic fundoplication: the alternative to long-term medical therapy for
      severe gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease is common. Fundoplication is very effective for
      those patients who fail medical therapy, particularly those with an incompetent
      lower esophageal sphincter. Open surgery is reported to achieve cure rates in
      excess of 90 percent. Laparoscopic fundoplication has been performed since 1991.
      The early experience with this procedure is reviewed. RESULTS: 1992 cases were
      reported in the literature. The mortality rate was 0.1 percent. Operative
      complications occurred as follows: 0.9 percent esophagogastric perforation rate;
      0.6 percent bleeding rate (requiring transfusion); and 0.6 percent pneumothorax
      rate. No splenectomies were reported. 4.8 percent of patients required conversion
      to the open procedure. As experience with the procedure is gained this conversion
      rate decreases. Recurrent reflux postoperatively is 3.4 percent, but follow-up is
      short (range: 0 to 36 months; mean: two years). Dysphagia requiring dilatation
      occurs in 3.5 percent of patients. Gas bloat occurs in 0 to 24 percent of
      patients. These results compare favorably with the published results of medical
      therapy and the open fundoplication. CONCLUSIONS: The early experience with
      laparoscopic fundoplication appears promising and provides an attractive
      alternative to long-term medical therapy and to open surgery in appropriate
      patients. Long-term follow-up is awaited.

PMID- 9165698
TI  - Is gastrinoma a medical disease?
AB  - Zollinger-Ellison syndrome (ZES) is a rare disease. Its management concerns
      symptoms related to the gastric acid overproduction that characterizes the
      syndrome and to the gastrin-producing tumor(s) usually located in the duodenal
      wall and/or the endocrine pancreas. Acid hypersecretion is now controlled by the
      use of powerful antisecretory agents. Management of the malignant process(es) has
      become the primary goal of modern strategy: it aims first at curing the disease
      and second at prolonging patient survival by prevention of hepatic metastasis. In
      patients with the sporadic form of the disease and without liver metastases, it
      is currently possible to localize and to surgically remove the endocrine
      tumor(s). This progress has been made feasible by refinements in modern medical
      imaging. At present, however, disease cure, even in the most favorable
      conditions, is not be greater than 30 to 50 percent at five years. In patients
      with ZES integrated in the context of multiple endocrine neoplasia type I,
      disease cure rate is extremely low, although occasional patient survival can be
      as good or even better than in the sporadic group. Disseminated malignancy (liver
      and/or extra-abdominal lymph nodes or bone localization) remains the principal
      determinant of early death. Surgical treatment is usually precluded in such
      cases. Liver transplantation has not been successful in these patients.

PMID- 9165699
TI  - Acid, protons and Helicobacter pylori.
AB  - The anti-ulcer drugs that act as covalent inhibitors of the gastric acid pump are
      targeted to the gastric H+/K+ ATPase by virtue of accumulation in acid and
      conversion to the active sulfenamide. This results in extremely effective
      inhibition of acid secretion. Appropriate dosage is able to optimize acid control
      therapy for reflux and peptic ulcer disease as compared to H2 receptor
      antagonists. However, clinical data on recurrence show that Helicobacter pylori
      eradication should accompany treatment of the lesion. These drugs have been found
      to synergize with many antibiotics for eradication. The survival of aerobes
      depends on their ability to maintain a driving force for protons across their
      inner membrane, the sum of a pH and potential difference gradient, the
      protonmotive force (pmf). The transmembrane flux of protons across the F1F0
      ATPase, driven by the pmf, is coupled to the synthesis of ATP. The internal pH of
      H. pylori was measured using the fluorescent dye probe, BCECF, and the membrane
      potential defined by the uptake of the carbocyanine dye, DiSC3 [5] at different
      pHs to mimic the gastric environment. The protonmotive force at pH 7.0 was
      composed of a delta pH of 1.4 (-84mV) and a delta potential difference of -131mV,
      to give a pmf of -215 mV. The effect of variations in external pH on survival of
      the bacteria in the absence of urea correlated with the effect of external pH on
      the ability of the bacteria to maintain a pmf. The effect of the addition of 5 mM
      urea on the pmf was measured at different medium pH values. Urea restored the pmf
      at pH 3.0 or 3.5, but abolished the pmf at pH 7.0 or higher, due the production
      of the alkalinizing cation, NH3. Hence H. pylori is an acid-tolerant neutrophile
      due to urease activity, but urease activity also limits its survival to an acidic
      environment. These data help explain the occupation of the stomach by the
      organism and its distribution between fundus and antrum. This distribution and
      its alteration by proton pump inhibitors also explains the synergism of proton
      pump inhibition and antibiotics such as amoxicillin and clarithromycin in H.
      pylori eradication.

PMID- 9165700
TI  - Polygalacturonase isolated from the culture of the psychrophilic fungus
      Sclerotinia borealis.
AB  - A polygalacturonase was isolated from the culture medium of Sclerotinia borealis,
      a psychrophilic fungus that grows on lawn and wheat seedling under the snow in
      winter and induces the snow mold disease. Pectic acid was a better substrate of
      this enzyme than pectin when the activity was determined by measuring the
      reducing sugar produced. However, when the activity was measured by viscosity
      change, the viscosity of pectin decreased more rapidly than that of pectic acid.
      The results of viscosity change apparently indicate that the polygalacturonase
      catalyzes pectin hydrolysis as an endo-type enzyme. Highly methyl-esterified
      pectin was a poor substrate, as determined by measurements of reducing sugar
      production and viscosity change. It is suggested from the results that the
      methoxy group of pectin affects the polygalacturonase reaction. A reaction
      mechanism was proposed for the polygalacturonase reaction. Molecular mass of this
      enzyme was 40 kDa and its isoelectric point was pH 7.5. Optimum pH of the enzyme
      reaction was 4.5 and its optimum temperature was 40-50 degrees C. Thirty percent
      of the maximum activity was observed at 5 degrees C, but it was only slightly
      active above 60 degrees C. The activity was preserved for more than 2 years at 5
      degrees C and pH 4.5, but it was lost when kept at room temperature overnight or
      heated at 50 degrees C for 30 min. The amino acid sequence of the N-terminal
      region of the psychrophilic polygalacturonase of Sclerotinia borealis is compared
      with those of polygalacturonases of mesophilic fungi. The function of this enzyme
      against the target plants is discussed with reference to the reaction of
      polygalacturonases of mesophilic fungi.

PMID- 9165701
TI  - Identification of gene loci controlling pectate lyase production and soft-rot
      pathogenicity in Pseudomonas marginalis.
AB  - Pseudomonas marginalis is an important postharvest pathogen capable of causing
      soft rot in a wide variety of harvested fruits and vegetables. Following
      transposon mutagenesis, we isolated two groups of P. marginalis CY091 mutants
      deficient in production of pectate lyase (Pel) and soft-rot pathogenicity in
      plants. The first group, designated Pel-, was caused by the insertion of Tn5 into
      a pel structural gene, and the second group, designated LemA-, was caused by the
      insertion of Tn5 into a regulatory locus corresponding to the lemA gene
      previously identified in other Gram-negative bacteria. The LemA- mutants also
      exhibited alteration in colony morphology and showed deficiency in production of
      protease (Prt). A cosmid clone pCIC carrying the P. marginalis lemA gene was
      isolated and characterized. pCIC was capable of restoring Pel production and soft
      rot pathogenicity in LemA- mutants of P. marginalis and Pseudomonas viridiflava,
      indicating that the function of lemA gene in these two pseudomonads was similar
      and interchangeable. Using MudI-mediated mutagenesis, we isolated a third group
      of P. marginalis mutants deficient in production of Pel, Prt, and soft-rot
      pathogenicity. Mutants in this group (designated GacA-1) contained an insertion
      of MudI in a locus corresponding to the gacA gene of P. viridiflava. Like LemA-
      mutants, GacA- mutants also exhibited alteration in colony morphology and showed
      deficiency in production of Pel and Prt. However, GacA- mutants produced much
      lower levels of levan and fluorescent pyoverdine siderophore than the wild type
      and LemA- mutants. These results provide the first genetic evidence that P.
      marginalis produces a single alkaline Pel for maceration of plant tissue and
      demonstrate that production of Pel, Prt, levan, and pyoverdin by this bacterium
      is mediated by the two-component lemA/gacA gene system.

PMID- 9165702
TI  - A simple method for enumerating bacteriophages in soil.
AB  - A plaque technique that uses antibiotic-resistant bacteria growing on antibiotic
      containing agar for the assay lawn resulted in significantly better recovery of
      bacteriophages P1 of Escherichia coli and F116 of Pseudomonas aeruginosa from
      nonsterile soil than standard membrane filtration or centrifugation techniques.
      Adsorption of the phages on soil particles appeared to be involved in their
      recovery and survival in soil.

PMID- 9165704
TI  - Induction of desiccation tolerance by osmotic treatment in Saccharomyces uvarum
      var. carlsbergensis.
AB  - Saccharomyces uvarum var. carlsbergensis is heat sensitive and when dried by
      usual procedures exhibits very poor survival. Our results demonstrate that these
      cells are capable of accumulating trehalose when submitted to an osmotic
      treatment using 20% solutions of either sorbitol or dextrin endowing them with
      the capacity of surviving posterior dehydration.

PMID- 9165703
TI  - An endoglucanase from the anaerobic fungus Orpinomyces joyonii: characterization
      of the gene and its product.
AB  - An endoglucanase gene (celA) was isolated from a genomic library of the ruminal
      fungus Orpinomyces joyonii. DNA sequence analysis of celA revealed an intronless
      gene encoding a typical signal sequence, an N-terminal catalytic domain, two
      repeated regions linked by a short Ser/Thr-rich linker and a domain of unknown
      function. The deduced amino acid sequence of the catalytic domain showed homology
      with the family 5 cellulases. While the catalytic domain of CelA was not
      homologous to the catalytic domain of the endoglucanase gene (EG3) from the
      ruminal bacterium Fibrobacter succinogenes, the repeated regions of CelA were
      very similar to the noncatalytic domain of EG3. This suggests that evolutionary
      shuffling of endoglucanase domains might occur among bacteria and fungi within
      the anaerobic ecosystem of the rumen. The celA gene was expressed in Escherichia
      coli, and the periplasmic endoglucanase was used for the characterization studies
      of the enzyme. CelA exhibited both endoglucanase and xylanase activities. Its pH
      optimum was 4 and the temperature optimum was 40 degrees C. Deletion analysis
      showed that the repeated sequences and C-terminal domain of CelA were not
      required for enzyme activity.

PMID- 9165705
TI  - Environmental mycobacteria in bottled table waters in Greece.
AB  - A hundred and fifty samples of bottled table water sold by Greek factories were
      examined for the presence of environmental mycobacteria. Environmental
      mycobacteria were found in 23 (15.6%) of the 150 tested samples. Bacterial
      numbers of 1-100, 101-300, 301-1000, and > 10(3) CFU/L were found in 8, 2, 1, and
      4% of the samples, respectively. The identification of the environmental
      mycobacteria was performed by both polymerase chain reaction-restriction enzyme
      analysis (PCR-REA) and biochemical methods. The environmental mycobacteria found
      were 14 Mycobacterium chelonae, 3 Mycobacterium phlei, 4 Mycobacterium gordonae,
      and 2 Mycobacterium flavescens. The relatively high number of environmental
      mycobacteria in bottled table water leads us to believe that the search of these
      opportunistic microorganisms in bottled water could be a useful index of their
      hygienic quality when this water is to be consumed by immunologically compromised
      patients. No statistically significant correlation was found between the presence
      of mycobacteria and the bacteriological faecal indicators (P < 0.005).

PMID- 9165706
TI  - Direct and indirect stimulus-frequency effects in recognition.
AB  - Subsequent recognition of stimuli perceived in a given situation was studied in
      relation to stimulus familiarity as determined by frequency in observers' prior
      experience. To distinguish direct and indirect frequency effects, on the basis of
      selective memory retrieval and selective attention during learning, respectively,
      rigorous controls were imposed on stimulus rehearsability and learning
      conditions. As predicted by a global memory model, both hits and false alarms on
      recognition tests increased as a function of prior frequency in a concordant
      pattern that indicates a direct effect, in contrast with the usual indirect
      effect of varying normative word frequency. Understanding the role of
      experiential stimulus frequency in recognition may further the interpretation of
      research in such paradigms as eyewitness testimony.

PMID- 9165707
TI  - Heuristics and biases in the "eyeballing" of data: the effects of context on
      intuitive correlation assessment.
AB  - For a wide variety of real-world decisions, people must examine numerical tables
      and intuitively assess the correlations that exist among meaningful variables.
      The normative properties of correlation coefficients suggest that such decisions
      should be unaffected by perceptual factors (e.g., changes in row and column
      locations), semantic factors (e.g., the referents of the numbers), or certain
      transformations of the variables (e.g., adding a constant or multiplying by a
      constant). Four experiments demonstrated that judgments based on perceived
      correlations violate these normative properties. A general model of intuitive
      covariation assessment was proposed to explain the observed biases. Estimation of
      this model at the aggregate and individual levels suggested that no single
      heuristic is consistent with all of the results. Instead, the existence of
      several qualitatively different types of heuristics was supported. The
      distribution of individual-level decision rules across types of heuristics was
      systematically related to contextual factors.

PMID- 9165708
TI  - The metrics of spatial situation models.
AB  - The authors investigated the metrics of spatial distance represented in situation
      models of narratives. In 3 experiments, a spatial gradient of accessibility in
      situation models was observed: The accessibility of objects contained in the
      situation model decreased with increasing spatial distance between the object and
      the reader's focus of attention. The first 2 experiments demonstrated that this
      effect of spatial distance was purely categorical rather than Euclidean:
      Accessibility depended on the number of rooms located between the object and the
      focus of attention, not on the size of the rooms. Experiment 3 revealed, however,
      that participants were able to use information about Euclidean distance in a
      secondary task when necessary. The implications of these results for theories of
      narrative comprehension and hierarchical versus nonhierarchical theories of
      spatial memory are discussed.

PMID- 9165709
TI  - The role of component function in visual recognition of Chinese characters.
AB  - M. Taft and X. Zhu (1997) reported that character decision latencies to real
      Chinese characters containing components that entered into many combinations were
      faster than decision latencies to characters with components that entered into
      only a small number of combinations. However, this effect was restricted to
      components that appeared on the right side of Chinese characters. In written
      Chinese, phonetic components tend to appear on the right, and semantic components
      tend to appear on the left. Therefore, in Taft and Zhu's study, there was the
      possibility of a confound between position (left vs. right) and function
      (semantic vs. phonetic). Results of the present experiment show combinability
      effects for components with semantic and with phonetic functions. Counter to the
      claim by Taft and Zhu that component frequency effects are constrained by
      position, when component function was considered, character decision latencies
      varied with component frequency but not reliably with position.

PMID- 9165710
TI  - X-ray microanalysis of uterine secretion in the mouse.
AB  - In an attempt to characterize ion transport mechanisms in the uterine epithelium
      the effect of diuretics on the elemental composition of the uterine secretion was
      investigated by X-ray microanalysis. Mice were treated with a variety of
      diuretics and Sephadex beads were incubated in situ in the uterus where they
      absorbed the uterine secretion. In animals treated with furosemide, bumetanide,
      or amiloride, the concentration of Na, K, and Cl in the uterine secretion was
      significantly decreased. After treatment with acetazolamide, only the K
      concentration was significantly decreased. Treatment with diuretics also
      decreased the concentration of P and S in the uterine secretion, indicating that
      less mucus was absorbed to the Sephadex beads. Transmission electron microscopy
      confirmed that treatment with amiloride and furosemide decreased the amount of
      mucus covering the epithelium. A possible explanation is that because of lack of
      water, the uterine mucus cannot leave the lumen of the uterine glands and reach
      the surface of the epithelium where the beads are. The data strongly suggest that
      Na+, K+, and Cl- transport in the uterine epithelium is dependent on a
      basolaterally situated Na(+)-(K+)-Cl(-)-cotransport mechanism. Disturbance of
      normal ion and water transport apparently affects the composition and consistency
      of the mucus, which may help explain abnormalities in cervical mucus in patients
      with cystic fibrosis.

PMID- 9165711
TI  - Effects of nicotine on the uterine epithelium studied by X-ray microanalysis.
AB  - The composition of the uterine fluid is of importance for the development of the
      embryo. The ionic composition of the uterine fluid is determined by transport
      processes in the uterine epithelium. The aim of the present study was to
      investigate whether nicotine can affect the ion transport processes and
      ultrastructure of the uterine epithelium in mouse and rat. The effects of
      nicotine on the uterine epithelium were compared with those on kidney and liver.
      Nicotine was administered to mice as an intraperitoneal injection of a 1
      microgram/l nicotine solution twice daily for 8 days, or in the drinking water
      (108 microM nicotine) for 15 days, whereas rats received nicotine in their
      drinking water for 10 days (54 or 108 microM nicotine). In addition, primary
      cultures of endometrial cells were exposed to nicotine in vitro. Changes in
      morphology were examined by transmission electron microscopy and changes in
      elemental content by X-ray microanalysis. Nicotine caused a significant decrease
      in the concentrations of Na, K, and Cl in the uterine fluid and in the
      endometrial cells in situ. Similar changes in elemental concentrations were
      observed in endometrial cells in vitro. Ultrastructural changes in endometrial
      cells included swollen and damaged mitochondria. In liver and kidney much smaller
      effects of nicotine on the elemental composition of the cells were observed.
      However, marked ultrastructural effects were seen in the kidney: a reduction in
      mitochondrial size and an increase in lysosomal volume. It is concluded that
      nicotine directly interferes with fluid transport across the uterine epithelium.

PMID- 9165713
TI  - Ultrastructural identification of Sertoli cells in the semen of subfertile men.
      About four cases.
AB  - In this work Sertoli cells were identified in the semen of subfertile men using
      transmission electron microscopy. This observation is rare and has only been
      reported before once. These results would favour of seminiferous epithelium
      alterations and could be correlated with the presence of immature seminal line
      elements or non sperm cells in prospective studies.

PMID- 9165712
TI  - Ultrastructural evidence for divergent and alternating differentiations in
      spindle cell sarcoma xenografts.
AB  - Seven spindle cell sarcomas, 5 poorly differentiated ones and 2 moderately well
      differentiated ones, were established on nude mice and long term passaging was
      done. Sarcoma strains were analysed electron microscopically in an attempt to get
      further insight in spindle cell sarcoma differentiation pathways.
      Ultrastructurally, the tumours were classified as malignant peripheral nerve
      sheath tumour (3/7), leiomyosarcoma (2/7), rhabdomyosarcoma (1/7), and spindle
      cell sarcoma not otherwise classifiable (1/7). Undifferentiated tumour cells
      including fibroblastoid ones predominated in most xenografts, whereas cells
      harbouring cytoplasmic specificities tended to be few in number. Nevertheless,
      divergent differentiations exhibiting unusual double or triple patterns could be
      documented ultrastructurally in 12/30 xenografts with juxtaposed myomatous as
      well as nerve sheath-like cells and, in addition, histiocytoid (MFH-like)
      elements in 3 of the xenografts. Moreover, sarcoma strains alternated fine
      structural constellations in the course of passaging, whereby different
      phenotypes, myomatous, nerve sheath-like, unspecific, or mixed ones, succeeded
      one another. These findings pursue recent immunohistochemical data on
      multidirectional sarcoma differentiation by means of electron microscopy. They,
      furthermore, fit well into the concept of multipotential stem cells as
      progenitors in mesenchymal differentiation and suggest microenvironment to play a
      modifying role in the expression of cell differentiation.

PMID- 9165714
TI  - The three-dimensional architecture of the myosalpinx in the cow as revealed by
      scanning electron microscopy.
AB  - The three-dimensional architecture of the myosalpinx in the cow has been
      investigated by means of scanning electron microscopy after removal of
      interstitial connective tissue with NaOH digestion. In the extramural portion of
      the tubo-uterine junction, in the isthmus and ampulla, the myosalpinx is made up
      of oblique bundles of variable orientation and length, which are loosely
      distributed in the tubo-uterine junction and densely packed in both isthmus and
      ampulla. These bundles intersect and merge into the surrounding musculature. Our
      observations demonstrate how myosalpinx consists mainly of bundles of muscular
      fibers independent one of another, which show a multiple spatial arrangement and
      form a complex network. Such a muscular architecture is likely more suitable for
      stirring rather than pushing the embryos and gametes through the tube.

PMID- 9165715
TI  - Ultrastructural evidence for association of vascular dendritic cells with T
      lymphocytes and with B-cells in human atherosclerosis.
AB  - It has been previously demonstrated that dendritic cells are involved in human
      atherogenesis and immunohistochemical analysis indicated that S100+/CD1a+
      vascular dendritic cells co-localize with lymphocytes in atherosclerotic lesions.
      Despite the high frequency of co-localization of vascular dendritic cells and
      lymphocytes in cell-rich areas, different type intimal cells were often
      intermingled and very closely apposed, which precluded determining whether
      vascular dendritic cells and lymphocytes specifically contacted each other or
      were simply densely packed together. Therefore, we undertook the present
      electronmicroscopical examination to see if vascular dendritic cells form direct
      contacts with lymphocytes in human atherosclerotic lesions. Serial sectioning of
      lymphocyte-rich areas of the human atherosclerotic aortas showed that vascular
      dendritic cells exhibiting a well developed tubulovesicular apparatus were
      located amongst T-lymphocytes and that through their processes, vascular
      dendritic cells formed multiple contacts with T-lymphocytes. In these contacts,
      vascular dendritic cell processes exhibited hypertrophied cisterns of the
      tubulovesicular system, which suggests the activation of vascular dendritic
      cells. From our observations we speculate that vascular dendritic cells may be
      responsible for the survival and activation of T-lymphocytes since a large number
      of T-lymphocytes which did not form contacts with vascular dendritic cells were
      found to have undergone destruction in atherosclerotic lesions. B-cells (plasma
      cells) were rarely seen in atherosclerotic lesions but vascular dendritic cells
      were found to form direct contacts with them. That vascular dendritic cells
      contact with both the T- and B-cells suggests that these vascular dendritic cells
      differ from other dendritic cells, subtypes of which are associated with T-cells
      (Langerhans cells, interdigitating cells) or with B-cells (follicular dendritic
      cells).

PMID- 9165716
TI  - Apoptotic cells in peripheral blood from patients with low serum cobalamin.
AB  - Apoptotic leukocytes were found by using ultrastructural and light microscopic
      techniques to examine peripheral blood in ten of twelve patients with low serum
      cobalamin (vitamin B12) and rarely in normal controls. A total of 88 apoptotic
      cells (.14% of total leukocytes) were identified in all the patients. One patient
      also had apoptotic cells found on a routine blood smear. There was no correlation
      between the finding of these cells and nuclear hypersegmentation, serum cobalamin
      levels, serum intrinsic factor antibody, serum methylmalonic acid and
      homocysteine or the Schilling test. Two patients, however, with the most severe
      vitamin deficiency did not have increased numbers of apoptotic cells suggesting
      that these patients had lost the ability to initiate the cell death program.

PMID- 9165717
TI  - Concomitant endosome-phagosome fusion and lysis of endosomal membranes account
      for Pseudomonas aeruginosa survival in human endothelial cells.
AB  - P. aeruginosa is selectively internalized by human endothelial cells but is not
      efficiently killed in the intracellular (IC) compartment. To investigate whether
      IC survival is associated with failure in bacteria-containing endosome-lysosome
      (E-L) fusion, endothelial cells were exposed to albumin-colloidal gold complex
      and to bacterial suspension and submitted to transmission electron microscopy
      (TEM). Gold granules were detected in P. aeruginosa-containing vacuoles,
      indicating that E-L fusion had occurred. Bacteria were also seen apparently free
      in the cell cytoplasm, suggesting disruption of endosome membranes. To ascertain
      whether phospholipase C (PLC) could account for vacuolar lysis, PLC producing
      PAO1 and PAK strains were compared with a PLC deficient mutant (PLCN) in their IC
      survival. All three strains were equally uptaken by the endothelial cells, as
      determined by the gentamicin exclusion assay. After 3 h of infection, the IC
      concentration of PAK and PAO1 increased significantly while the concentration of
      the mutant decreased to 56.8 +/- 18.2% of the viable counts at 1 h of infection.
      After 5 h, the IC concentration of P. aeruginosa corresponded to 83.1 +/- 34.6%,
      109 +/- 22.6% and 26.2 +/- 14.7% of the viable counts detected at 1 h, for PAK,
      PAO1 and the mutant, respectively. By TEM, while most PAO1-containing vacuoles
      presented partially lysed membranes, in cells infected with the PLCN mutant
      bacteria were most often observed in vacuoles with intact membranes. These
      observations suggest that the IC survival of P. aeruginosa results from a
      competition between the microbicidal activity of endothelial cells following E-L
      fusion and the capacity of bacteria to escape from endosomes.

PMID- 9165718
TI  - Ultrastructural localization of blood group antigens in human exocrine pancreas
      by immunogold labelling.
AB  - The cytochemical distribution of ABH and Lewis antigens was investigated in human
      pancreas by means of a post-embedding immunogold staining method which permitted
      antigens associated with secretory materials to be distinguished from those bound
      to cell surfaces. H and Le-b antigens were found in secretory granules of acinar
      and interlobular duct cells. In the form of surface-associated antigens, H and Le
      b were found in acini and interlobular ducts, Le-a in intralobular ducts. In
      ductal cells, the same antigens detected in cell surfaces were also found in
      small cytoplasmic vesicles. It is suggested that by the emptying of these
      vesicles blood group antigens may be released both into the lumen and into the
      interstitial spaces.

PMID- 9165719
TI  - Propranolol-like action of amiodarone. An electronmicroscopic study in rats under
      cold stress.
AB  - The cold stress leads to increased levels of catecholamines, of their precursors
      and metabolites, with increased oxygen consumption by the myocardium. Atrial
      cardiomyocytes of amiodarone-treated rats, previously stressed by cold, showed a
      marked decrease of the morphological alterations observed in the animals
      submitted to cold stress without amiodarone protection. Such results indicate, at
      the subcellular level, that amiodarone could improve cardiac function by a
      propranolol-like action when there is heart failure, a condition in which there
      is a high level of catecholamine.

PMID- 9165720
TI  - Contribution of capillary endothelium to cor pulmonale development in
      experimental lung emphysema.
AB  - The aim of this study was the ultrastructural analysis of the changes in the
      endothelium of myocardial capillaries and the processes observed in their
      vicinity in consecutive stages of experimental lung emphysema. Emphysematous
      changes in the lungs of Wistar rats were induced with a single intraperitoneal
      infusion of proteolytic enzyme solution, papain, in a dose of 20 mg/kg b.w./0.5
      ml PBS. Ultrastructural analysis of the changes within the right ventricle and
      the subendocardial part of the left ventricle of the heart was made by a
      transmission electron microscope after 1, 3 and 6 months following papain
      administration. Special attention was paid to the analysis of changes found in
      the vicinity of newly formed myocardial capillaries. Animals killed after 1 and 3
      months following papain infusion showed blurred borderline between the
      endothelium of the newly formed myocardial capillaries and perivascular
      connective matrix. The new vessels had poorly developed basement membrane.
      Fibrillary structures and/or collagen fibrils were found instead. The latter
      frequently demonstrated features of disorders in the structure and spatial
      distribution. Neither fibroblasts nor their processes were observed in the
      vicinity of the new collagen fibrils. Pericytes were occasionally present. In the
      later period (6 months from intratracheal papain infusion) well formed collagen
      fibres dominated in the vicinity of myocardial capillaries. The results of the
      ultrastructural analysis suggest the possibility of active contribution of
      endothelial cells to the processes of perivascular fibrosis within the myocardium
      in the course of experimental lung emphysema.

PMID- 9165721
TI  - Ultrastructural and morphometric aspects of ageing in the retinal capillaries of
      rats.
AB  - Age-related morphological, ultrastructural and morphometric changes in the
      capillaries of the superficial and deep plexuses of the rat retina were studied
      in animals aged from 3 to 15 months. Our results suggest that age-related
      morphological alterations start occurring in the retina of rats at about 12
      months of age. Increased glycogen deposits, pinocytotic vesicles, residual bodies
      and cell debris were observed in both the endothelial and pericytic cells of 12-
      and 15-month-old animals. In addition, heterogeneous osmiophilic accumulations,
      electron-transparent spaces were observed in the basement membrane as well as
      projections of the basement membrane towards the neighboring cells. Morphometric
      examination of the two vascular plexuses studied did not show differences in the
      area of the endothelial or pericytic cells, basement membrane or vascular lumen
      between rats of different ages.

PMID- 9165722
TI  - Room noise criteria--the S12.2-1995 standard raises serious technical and
      economic considerations.
AB  - The key issue with the S12.2-1995 standard is not the differences in the
      assessment of sound quality, particularly at the low frequencies, but rather the
      use of octave-band data to describe low-frequency equipment misbehavior.
      Unfortunately, the "NCB vs RC" controversy leads research efforts and technical
      discussions in the wrong directions, disregarding serious economic and technical
      considerations. This conflict can be resolved by: (1) avoiding the use of octave
      band data to rate noise with abnormal (spectral and/or temporal) characteristics,
      (2) addressing the widespread need for the room noise criteria as a practical
      design tool for general use in architectural spaces, and (3) developing adequate
      descriptor/procedures to qualify, quantify, and determine the impact of "rumble"
      on human response. A further goal should be to develop integrated criteria that
      would apply to both HVAC and computer noise sources.

PMID- 9165723
TI  - Some hot topics in animal bioacoustics.
AB  - This paper is derived from a "Hot Topics in Animal Bioacoustics" presentation at
      the 130th meeting of the Acoustical Society of America in St. Louis, Missouri.
      Six bioacoustics studies on a wide variety of species are discussed. Two of the
      studies are concerned with insects, the parasitoid fly, and cotton bollworms. The
      remaining bioacoustics studies are on aquatic animals including the West Indian
      manatee, elephant seals, and dolphins.

PMID- 9165724
TI  - Radiation force on a spherical object in the field of a focused cylindrical
      transducer.
AB  - An exact solution of the radiation force on a spherical object, when positioned
      on the acoustic axis of a cylindrical transducer, is provided. The solution is
      valid for any type of sphere of any size. The radiation force function allows the
      calibration of high-frequency focused ultrasound fields from radiation force
      measurements and expands the utility of the elastic sphere radiometer developed
      by Dunn et al. [Acustica 38, 58-61 (1977)]. Numeral results reveal an oscillatory
      behavior of the radiation force function for small spheres near the transducer
      surface and this behavior may present an opportunity for particle sorting based
      on the mechanical properties of the particle and other types of manipulation.

PMID- 9165725
TI  - Annoyance caused by sounds of wheeled and tracked vehicles.
AB  - In a laboratory experiment, the relationship between the annoyance caused by
      sounds of tracked and wheeled vehicles was investigated. Sounds of various
      vehicles, ranging from a main battle tank (MBT) to a passenger car, were recorded
      at several distances. Subjects were presented with these sounds and were asked to
      judge the annoyance if they were exposed to them at home on a regular basis.
      Overall, sounds emanated from military tracked vehicles were judged to be less
      annoying than civil passenger cars, provided that the indoor A-weighted sound
      exposure levels (ASELs) were the same. It should be noted that receiver distance
      and operating conditions were not specifically matched for military and civil
      vehicles but were chosen to represent typical ranges of values found in practice.
      For steady-speed conditions, the sounds were judged to be equally annoying if the
      (indoor) ASELs of the tracked armored personnel carrier (APC) and the MBT
      exceeded that of a passenger car by 5 and 10 dB, respectively. In specific
      driving conditions such as alternate accelerations and decelerations, however,
      these differences were smaller. For ASELs below 55 dB, passenger cars were found
      to be more annoying than heavier wheeled vehicles, such as a bus or a truck with
      a trailer. The data indicate that the difference between the high-frequency part
      and the low-frequency part of the spectrum might play a role in the annoyance.
      With respect to noise-zoning procedures it is highly interesting that the outdoor
      ASEL could predict the annoyance, as rated indoors, better than could any indoor
      noise measure. The 5- and 10-dB bonuses to the indoor level of the APC and the
      MBT, respectively, were reduced to 1 and 3 dB if the dose was measured outdoors.

PMID- 9165726
TI  - Spectral cues for sound localization in cats: a model for discharge rate
      representations in the auditory nerve.
AB  - Neural representations of pinna-based spectral cues for sound localization were
      modeled by simulating auditory nerve discharge rates to noise bursts that had
      been shaped by filtering properties of the cat's head-related transfer functions
      (HRTFs) at 179 locations in the frontal field. The auditory nerve model
      transformed spectral differences between HRTFs into simulated neural rate
      differences. Linear equations for this transformation were developed from actual
      auditory nerve responses to a limited subset of HRTF-filtered noise bursts [Rice
      et al., J. Acoust. Soc. Am. 97, 1764-1776 (1995)]. Signal detection methods were
      used to investigate simulated neural responses to pairwise changes between HRTFs.
      The quality of neural representation for these changes, in terms of d' values,
      declined when the reference HRTF was moved from a central location (0 degree AZ,
      0 degree EL) to a large positive azimuth in the horizontal plane (75 degrees AZ,
      0 degree EL) or a high elevation in the median plane (0 degree AZ, 75 degrees
      EL). Most simulated responses exhibited large d' values for comparisons of
      contralateral versus ipsilateral azimuths, or eccentric versus frontal
      elevations. This rate information resulted from directionally dependent changes
      in the overall gain of HRTFs. In addition, fibers with best frequency (BF: the
      frequency of greatest sensitivity for individual fibers) between 5 and 18 kHz
      showed large d' values for HRTF contrasts in the immediate frontal field because
      of the effects of spectral notches (i.e., sharp drops in gain over a narrow
      frequency range). Spectral notches also played a prominent role in simulations
      that required identification of HRTF location in the absence of a fixed reference
      stimulus. These modeling results correspond well with previously described
      patterns in the cat's localization behaviors.

PMID- 9165727
TI  - Neural contributions to the perstimulus compound action potential: implications
      for measuring the growth of the auditory nerve spike count as a function of
      stimulus intensity.
AB  - The perstimulus compound action potential (PCAP), unlike the more familiar
      compound action potential (CAP), can be recorded in response to asynchronous as
      well as synchronous auditory nerve activity. When all neurons contribute equally
      to the PCAP, the area under the PCAP (the PCAP area) is proportional to the
      number of action potentials fired by auditory nerve neurons (the auditory nerve
      spike count). The auditory nerve spike count is one proposed code for stimulus
      intensity, and our goal is to use the PCAP to test this hypothesis. In this
      study, two independent tests were developed to measure the contributions of
      neurons to the PCAP as a function of their characteristic frequency (CF). The
      test results were verified using a model of the auditory periphery designed to
      calculate the auditory nerve spike count as a function of pure tone intensity and
      frequency. In nearly all experiments, neurons having CFs that span contiguous
      three or four octave bands contribute equally to the PCAP. For pure tones that
      stimulate only those neurons contributing equally to the PCAP, the PCAP area
      grows over intensity ranges frequently exceeding 80 dB, and in one case equaling
      108 dB. These results demonstrate that the auditory nerve spike count, at least
      for pure tones, is capable of encoding changes in stimulus intensity over the
      entire dynamic range of the auditory system.

PMID- 9165728
TI  - Is loudness simply proportional to the auditory nerve spike count?
AB  - It is often asserted that the physiological correlate of loudness is the simple
      sum of the spike activity produced by all neurons in the auditory nerve (the
      auditory nerve spike count). We will refer to this hypothesis as the spike count
      hypothesis. The spike count hypothesis has been tested in the past using models
      of the auditory periphery and in almost all cases, the hypothesis has been
      supported. Our new technique for recording a compound potential from the
      chinchilla auditory nerve, the perstimulus compound action potential (PCAP),
      makes possible the measurement of the growth of the auditory nerve spike count,
      thus providing data that can be used to test the spike count hypothesis
      empirically. It was observed that the growth of the auditory nerve spike count in
      response to a 1-kHz pure tone (in dB/dB) is 33% shallower than the growth of
      loudness for a 1-kHz tone, and this discrepancy increases to 66% for an 8-kHz
      tone. In addition, "equal-count" contours were constructed in a manner analogous
      to equal-loudness contours. It was found that as reference intensity increases,
      equal-count contours become sharply curved upward at high frequencies whereas
      equal-loudness contours become increasingly flat. These differences are unlikely
      to be the result of the cross-species comparison, since the discrepancies are
      mostly attributable to the skewed pattern of spread of excitation along the
      basilar membrane, a property shared by humans and chinchillas. Therefore, we
      conclude that the simple sum of the spike activity in the auditory nerve cannot
      be the physiological correlate of loudness.

PMID- 9165729
TI  - Efferent projections of a physiologically characterized region of the inferior
      colliculus of the young adult CBA mouse.
AB  - The present investigation is part of an ongoing series of studies aimed at
      discerning the neural bases of presbycusis. Presbycusis is a sensory perceptual
      disorder involving loss of high-pitch hearing and reduced ability to process
      biologically relevant acoustic signals in noisy environments. The purpose of the
      present experiment was to delineate the efferent projections of a functionally
      characterized region of the dorsomedial inferior colliculus (IC, auditory
      midbrain) in young, adult CBA mice. The CBA strain's progressive loss of hearing
      over its lifespan approximates many aspects of the mild-to-moderate hearing loss
      experienced by a significant number of humans suffering from presbycusis. Focal,
      iontophoretic injections of HRP were made in the 18-24 kHz region of dorsomedial
      IC of the CBA strain following physiological mapping experiments. Serial sections
      were reacted with a chromagen, counterstained and examined for anterogradely
      labeled fibers and boutons. Efferent projections were observed ipsilaterally in:
      medial and ventral divisions of the medial geniculate body (MGB); middle layers
      of the superior colliculus; central gray; and external nucleus (E), dorsal cortex
      (DC) and central nucleus of IC. Contralaterally, labeled fibers and boutons were
      seen in the IC at a location homologous to the injection site, as well as in E
      and DC. A small projection was noted in contralateral MGB. These findings in
      young, adult mice with normal hearing can now serve as a baseline for similar
      experiments being conducted in mice and animals of other species of older ages
      and with varying degrees of hearing loss.

PMID- 9165730
TI  - Sound-pressure measurements in the cochlear vestibule of human-cadaver ears.
AB  - The middle-ear pressure gain for the 50-Hz to 12-kHz range was determined from
      the ratio of sound pressures measured in the vestibule and the ear canal of four
      human-cadaver ears. The magnitude of the middle-ear pressure gain is 20 dB for
      frequencies between 500 Hz and 2 kHz. Above 4 kHz, the gain changes as a function
      of frequency at a rate of approximately -8 dB/octave and below 400 Hz at 4
      dB/octave. The standard error of the mean magnitude across the four ears is
      typically less than 3 dB. The phase angle of the pressure gain also changes with
      frequency. Interruption of the ossicular chain decreases the vestibule pressure
      by at least 20 dB. It is shown that air bubbles in the inner ear can diminish the
      vestibule pressure; procedures are used to remove bubbles. From these pressure
      measurements and previous measurements of stapes motion, the frequency dependence
      of behavioral thresholds for tones was tested to discover whether it corresponds
      to the constancy of a physiological variable at the cochlear input. Among
      pressure, power, or stapes-motion measures, the vestibule pressure is most nearly
      constant with frequency at the behavioral "minimum audible pressure."

PMID- 9165731
TI  - Click-evoked otoacoustic emissions and the influence of high-frequency hearing
      losses in humans.
AB  - Click-evoked otoacoustic emissions (cEOAEs) are thought to reflect the presence
      of highly tuned mechanisms involved in sound processing inside the cochlea. When
      the sensitivity and tuning of the inner ear are impaired in some frequency range,
      the spectral components of cEOAEs in the same frequency range are expected to be
      altered if the previous premise is correct. Although clinical experience does not
      contradict such an interpretation, fundamental aspects of cEOAE generation and
      propagation in the cochlea are not clear enough to preclude possible additional
      influences of remote cochlear places on cEOAE. In order to analyze this
      possibility, ultra-high-frequency hearing thresholds between 8 and 16 kHz were
      assessed in 43 human subjects that had clinically normal hearing thresholds in
      the frequency range of cEOAEs. The magnitude of their cEOAEs was found to be
      correlated to their average ultra-high-frequency hearing threshold, especially
      when ears presenting spontaneous otoacoustic emissions were not taken into
      account (p = 0.002, r2 = 0.29). Age and ultra-high-frequency hearing thresholds
      were correlated (p < 0.01, r2 = 0.40); thus it is not possible to exclude that
      aging was the primary cause of the observed trend. The contribution of ultra-high
      frequency hearing status to cEOAE magnitude, perhaps in relation to age, seems to
      explain a significant part of the variance of "normative" emission data and may
      be of interest for early detection of high-frequency hearing impairments.

PMID- 9165732
TI  - Relations between notched-noise suppressed TEOAE and the psychoacoustical
      critical bandwidth.
AB  - Narrow-band transitory evoked otoacoustic emissions (TEOAE) were recorded for
      nine normal hearing subjects in the presence of a broadband tone complex
      suppressor. Introducing a spectral notch at the frequency of the narrow-band
      stimulus causes the suppression effect to decrease, the more so the wider the
      notch. This decrease in suppression permits an estimate of the size of one
      critical band. One advantage of this approach is that no active participation of
      the subjects is required. The estimated critical bandwidth is then compared with
      independent estimates based on a simultaneous masking experiment, using the same
      stimuli. The two measures of the critical bandwidth coincide well for those six
      subjects with spontaneous otoacoustic emissions. However, the bandwidth estimate
      based on the OAE measurements is too large for the other three subjects without
      spontaneous emissions. Simulations of the suppression effect with a driven van
      der Pol oscillator with moderate undamping produce critical bandwidth estimates
      consistent with those observed in the psychoacoustical experiments. This allows
      an estimate of the "effective" amount of undamping on the basilar membrane that
      is required to produce the critical bandwidth observable in psychoacoustic
      experiments.

PMID- 9165733
TI  - A psychoacoustic model for the noise masking of plosive bursts.
AB  - A model for predicting the masked thresholds of the voiceless plosive bursts
      /k,t,p/ in background noise is proposed. Because plosive bursts are brief, are
      generated by a noise source, and have different spectral characteristics, the
      modeling approach accounts for duration, center frequency, and signal bandwidth.
      Noise-in-noise masking experiments are conducted using a broadband masker and
      bandpass noise signals of varying bandwidth (100-5483 Hz), duration (10-300 ms),
      and center frequency (0.4-4 kHz). Data from these experiments are used to
      parametrize an auditory filter model in which the effective bandwidth and the
      signal-to-noise ratio at threshold for each filter are duration dependent. The
      duration-dependent filter model is then used to predict the thresholds of
      synthetic and naturally spoken plosive bursts in background noise. Finally,
      results from pilot notched-noise experiments are presented which support duration
      dependent frequency selectivity.

PMID- 9165734
TI  - Spectral weights in level discrimination by preschool children: synthetic
      listening conditions.
AB  - On most auditory discrimination and detection tasks young children perform more
      poorly than adults. The current experiment applies a technique which potentially
      can reveal the extent to which the adult-child performance difference results
      from suboptimal attentional strategies or simply greater internal noise in the
      children. In this experiment preschool children and adults were asked to
      discriminate between complex tones comprised of three random-amplitude sinusoidal
      components. A trial-by-trial correlational analysis [R. A. Lutfi, J. Acoust. Soc.
      Am. 97, 1333-1334 (1995)] provided an estimate of the weight listeners placed on
      the level information from individual spectral components in making the
      discrimination. The patterns of weights were interpreted as measures of
      "attentional strategy." Both children and adults produced reliable patterns of
      weights. This is an especially important result since measuring a single
      weighting pattern requires large numbers of trials and hence multiple sessions
      with the children. While individual weighting patterns were reliable, weighting
      patterns differed both within and across groups. Moreover, neither the children
      nor the adults produced weighting patterns that would maximize percent correct in
      the task. A substantial proportion of the responses from both children and adults
      could be predicted from their weighting patterns even when performance was near
      chance. However, differences in overall performance between children and adults
      could not be accounted for by differences in their weighting functions.

PMID- 9165735
TI  - Spectral weights in level discrimination by preschool children: analytic
      listening conditions.
AB  - In this series of experiments, adult and child listeners were required to attend
      to a target tone in the presence of two distracters and to indicate in which of
      two intervals the target tone had the higher level. The attentional weight
      listeners placed on each component was estimated by computing the correlation
      between the level change of each component across intervals and the listener's
      response. In the first experiment, weights were obtained as a function of the
      mean level of the distracters (250 and 4000 Hz) for a 1000-Hz target. No
      consistent differences between the weighting functions of children and adults
      were observed. In a second experiment, weights were obtained as a function of the
      harmonic relationship between the distracters (250 and 4000 Hz, or 270 and 4320
      Hz) and the 1000-Hz target. No difference was observed between the weighting
      functions computed with harmonic and inharmonic complexes. In the final
      experiment, each component of the complex (250, 1000, and 4000 Hz) was identified
      as the target in separate blocks of trials. In general, adults were able to
      weight the target component appropriately regardless of its frequency, while
      children tended to weight all components equally. The results suggest that
      preschool listeners may exhibit poorer attentional selectivity than adults.

PMID- 9165736
TI  - Formant transition duration and speech recognition in normal and hearing-impaired
      listeners.
AB  - Listeners with sensorineural hearing loss often have difficulty discriminating
      stop consonants even when the speech signals are presented at high levels. One
      possible explanation for this deficit is that hearing-impaired listeners cannot
      use the information contained in the rapid formant transitions as well as normal
      hearing listeners. If this is the case, then perhaps slowing the rate of
      frequency change in formant transitions might assist their ability to perceive
      these speech sounds. In the present study, sets of consonant plus vowel (CV)
      syllables were synthesized corresponding to /ba, da, ga/ with formant transitions
      for each set ranging from 5 to 160 ms in duration. The listener's task was to
      identify the consonant in a three-alternative, closed-set response task. The
      results for normal-hearing listeners showed nearly perfect performance for
      transitions of 20 ms and longer, whereas the shortest transitions yielded poorer
      performance. A group of eight hearing-impaired listeners pure-tone averages
      (PTAs) ranging from 30 to 62 dB HL) was also tested. The hearing-impaired
      listeners tended to show poorer performance than the normals for transitions of
      all durations; however, the performance of a few hearing-impaired subjects was
      equal to that of normals for the shortest-duration transitions. A strong inverse
      relation was observed between degree of hearing loss and improvement in score as
      a function of transition duration. These results suggest that increasing the
      duration of formant transitions for listeners with more severe hearing losses may
      not provide a helpful solution to their speech recognition difficulties.

PMID- 9165737
TI  - An investigation of stop place of articulation as a function of syllable
      position: a locus equation perspective.
AB  - Locus equations were employed to phonetically describe stop place categories as a
      function of syllable-initial, -medial, and -final position. Ten speakers, five
      male and five female, produced a total of 2700 CVC and 4500 VCV utterances that
      were acoustically analyzed to obtain F2 onset, F2 vowel, and F2 offset
      frequencies for locus equation regression analyses. In general, degree of
      coarticulation, as indexed by locus equation slope, was reduced for post-vocalic
      (VC) stops relative to pre-vocalic stops (pooled data from initial and medial
      positions), but significant differences were observed as a function of stop
      consonant. All stops showed significantly reduced R2 values and increased
      standard errors of estimate for VC relative to CV productions. Separability of
      stop place categories in a higher-order slope X y-intercept acoustic space also
      diminished for VC vs CV stop productions. The degradation of classic locus
      equation form (high correlation and linearity) for VC relative to CV productions
      was attributed to greater articulatory precision in the production of pre-vocalic
      compared to post-vocalic stops. This greater articulatory precision was
      interpreted as reflecting a greater need to normalize vowel context-induced
      variability of the F2 transition for syllable onset relative to final stops. The
      decline in acoustic lawfulness of syllable-final stops is discussed in terms of
      coarticulatory interactions and expected perceptual correlates.

PMID- 9165738
TI  - Intraspeech spread of masking in normal-hearing and hearing-impaired listeners.
AB  - Hearing-impaired and normal-hearing listeners labeled synthetic consonant-vowel
      stimuli (/ba/, /da/, /ga/, /be/, /de/, /ge/) presented at moderate and high
      signal levels. First formant (F1) regions were synthesized at normal and at
      attenuated levels to test whether F1 attenuation might reduce upward spread of
      masking, making information contained in higher formant regions more available.
      Performance was tested in quiet and in broadband noise sufficient to mask initial
      release bursts. Although complete removal of F1 consistently reduced performance,
      F1 attenuation of up to 18 dB led to increased labeling accuracy, particularly in
      the /a/ vowel context. Benefit associated with F1 attenuation was more
      consistently seen for hearing-impaired than for normal-hearing listeners and, in
      particular, for listeners with steep increases in audiometric thresholds between
      the first and second formant regions of the test stimuli. The availability of
      initial bursts as a source of place cues during testing in quiet did not reduce
      the benefit associated with F1 attenuation.

PMID- 9165739
TI  - A targeting-and-extracting technique to enhance hearing in the presence of
      competing speech.
AB  - A targeting-and-extracting procedure of speech enhancement for hearing aids in
      the presence of background noise, especially competing speech, is proposed. The
      procedure is composed of two steps: targeting by a fixed (or deterministic)
      beamforming array, followed by a post-targeting extracting step. Emphasis is
      placed on the extracting step, which performs noise cancellation based on the
      acoustic difference between the desired speech and interfering speech. Either
      comb filtering or attenuation is applied to the signal in accordance with the
      current voiced/unvoiced/silence state of the desired signal. The comb filter
      design is based on the fundamental pitch frequency of the desired speech.
      Algorithms for deciding the voiced/unvoiced/silence state and determining the
      fundamental frequency are developed. The performance of the system is evaluated
      through computer simulation. The simulation results indicate significant noise
      cancellation and intelligibility improvement.

PMID- 9165740
TI  - Inertial cavitation and associated acoustic emission produced during
      electrohydraulic shock wave lithotripsy.
AB  - The inertial cavitation and associated acoustic emission generated during
      electrohydraulic shock wave lithotripsy were studied using high-speed photography
      and acoustic pressure measurements. The dynamics of cavitation bubble clusters,
      induced in vitro by an experimental laboratory lithotripter, were recorded using
      a high-speed rotating drum camera at 20,000 frames/s. The acoustic emission,
      generated by the rapid initial expansion and subsequent violent collapse of the
      cavitation bubbles, was measured simultaneously using a 1-MHz focused hydrophone,
      The expansion duration of the cavitation bubble cluster was found to correlate
      closely with the time delay between the first two groups of pressure spikes in
      the acoustic emission signal. This correlation provides an essential physical
      basis to assess the inertial cavitation produced by a clinical Dornier HM-3 shock
      wave lithotripter, both in water and in renal parenchyma of a swine model. In the
      clinical output voltage range (16-24 kV), the expansion duration of the primary
      cavitation bubble cluster generated by the HM-3 lithotripter in water increases
      from 158 to 254 microseconds, whereas the corresponding values in renal
      parenchyma are much smaller and remain almost unchanged (from 71 to 72
      microseconds). In contrast, subsequent oscillation of the bubble following its
      primary collapse is significantly prolonged (from 158-235 microseconds in water
      to 1364-1373 microseconds in renal parenchyma). These distinctive differences
      between lithotripsy-induced inertial cavitation in vitro and that in vivo are
      presumably due to the constraining effect of renal tissue on bubble expansion.

PMID- 9165741
TI  - The acoustic features of vowel-like grunt calls in chacma baboons (Papio
      cyncephalus ursinus): implications for production processes and functions.
AB  - The acoustic features of 216 baboon grunts were investigated through analysis of
      field-recorded calls produced by identified females in known contexts. Analyses
      addressed two distinct questions: whether the acoustic features of these tonal
      sounds could be characterized using a source-filter approach and whether the
      acoustic features of grunts varied by individual caller and social context.
      Converging evidence indicated that grunts were produced through a combination of
      periodic laryngeal vibration and a stable vocal tract filter. Their acoustic
      properties closely resembled those of prototypical human vowel sounds. In
      general, variation in the acoustic features of the grunts was more strongly
      related to caller identity than to the social contexts of calling. However, two
      acoustic parameters, second formant frequency and overall spectral tilt, did vary
      consistently depending on whether the caller was interacting with an infant or
      participating in a group move. Nonetheless, in accordance with the general view
      that identity cueing is a compelling function in animal communication, it can be
      concluded that much of the observed variability in grunt acoustics is likely to
      be related to this aspect of signaling. Further, cues related to vocal tract
      filtering appear particularly likely to play an important role in identifying
      individual calling animals.

PMID- 9165742
TI  - A backpropagation network model of the monaural localization information
      available in the bat echolocation system.
AB  - The information echolocating bats receive is a combination of the properties of
      the sound they emit and the sound they receive at the eardrum. Convolving the
      emission and the external ear transfer functions produces the full spectral
      information contained in the echolocation combination. Spatially dependent
      changes in the magnitude spectra of the emission, external ear transfer
      functions, and the echolocation combination of Eptesicus fuscus could provide
      localization information to the bat. Principal component analysis was used to
      reduce the dimensionality of these complex spectral data sets. The first eight
      principal component weights were normalized, rotated, and used as the input to a
      backpropagation network model which examined the relative directionality of the
      emission, ear, and the echolocation combination. The model was able to localize
      more accurately when provided with the directional information of the
      echolocation combination compared to either the emission or ear information
      alone.

PMID- 9165743
TI  - Acoustic effects of the ATOC signal (75 Hz, 195 dB) on dolphins and whales.
AB  - The Acoustic Thermometry of Ocean Climate (ATOC) program of Scripps Institution
      of Oceanography and the Applied Physics Laboratory, University of Washington,
      will broadcast a low-frequency 75-Hz phase modulated acoustic signal over ocean
      basins in order to study ocean temperatures on a global scale and examine the
      effects of global warming. One of the major concerns is the possible effect of
      the ATOC signal on marine life, especially on dolphins and whales. In order to
      address this issue, the hearing sensitivity of a false killer whale (Pseudorca
      crassidens) and a Risso's dolphin (Grampus griseus) to the ATOC sound was
      measured behaviorally. A staircase procedure with the signal levels being changed
      in 1-dB steps was used to measure the animals' threshold to the actual ATOC coded
      signal. The results indicate that small odontocetes such as the Pseudorca and
      Grampus swimming directly above the ATOC source will not hear the signal unless
      they dive to a depth of approximately 400 m. A sound propagation analysis
      suggests that the sound-pressure level at ranges greater than 0.5 km will be less
      than 130 dB for depths down to about 500 m. Several species of baleen whales
      produce sounds much greater than 170-180 dB. With the ATOC source on the axis of
      the deep sound channel (greater than 800 m), the ATOC signal will probably have
      minimal physical and physiological effects on cetaceans.

PMID- 9165744
TI  - The relationship between localization and the Franssen effect.
AB  - The relationship between localization and the Franssen effect was studied for
      noise and tones in a sound-deadened and in a live room. The noise was wideband
      and the tones were 250, 500, 1000, 1500, 2500, and 4000 Hz. Listeners were asked
      to determine the location of the stimuli in a localization task and to
      discriminate the difference between a pair of stimuli used to generate the
      Franssen illusion and a steady-state tone in a Franssen-effect discrimination
      task. Poor performance in the Franssen-effect discrimination task is consistent
      with the stimulus conditions leading to a strong Franssen illusion. Poor
      performance in both the Franssen effect and localization tasks was obtained for
      midfrequency tones (near 1500 Hz) and in the live room. Thus, the Franssen
      illusion is strongest for a live room and for midfrequency tones consistent with
      the difficulty listeners have in localizing sounds under these conditions. These
      results are consistent with those of Hartmann and Rakerd [J. Acoust. Soc. Am. 86,
      1366-1373 (1989)] and support their suggestion of a correlation between the
      Franssen effect and localization in rooms.

PMID- 9165745
TI  - Eyes off transcription! The wonderful world of post-transcriptional regulation.

PMID- 9165746
TI  - Regulation of photomorphogenesis by expression of mammalian biliverdin reductase
      in transgenic Arabidopsis plants.
AB  - The photoregulatory activity of the phytochrome photoreceptor requires the
      synthesis and covalent attachment of the linear tetrapyrrole prosthetic group
      phytochromobilin. Because the mammalian enzyme biliverdin IX alpha reductase
      (BVR) is able to functionally inactivate phytochromobilin in vitro, this
      investigation was undertaken to determine whether BVR expression in transgenic
      plants would prevent the synthesis of functionally active phytochrome in vivo.
      Here, we show that plastid-targeted, constitutive expression of BVR in
      Arabidopsis yields plants that display aberrant photomorphogenesis throughout
      their life cycle. Photobiological and biochemical analyses of three transgenic
      BVR lines exhibiting a 25-fold range of BVR expression established that the BVR
      dependent phenotypes are light dependent, pleiotropic, and consonant with the
      loss of multiple phytochrome activities. Chlorophyll accumulation in BVR
      expressing transgenic plants was particularly sensitive to increased light
      fluence rates, which is consistent with an important role for phytochrome in
      light tolerance. Under blue light, transgenic BVR plants displayed elongated
      hypocotyls but retained phototropic behavior and the ability to fully deetiolate.
      Directed BVR expression may prove to be useful for probing the cellular and
      developmental basis of phytochrome-mediated responses and for selective control
      of individual aspects of light-mediated plant growth and development.

PMID- 9165747
TI  - Collapsed xylem phenotype of Arabidopsis identifies mutants deficient in
      cellulose deposition in the secondary cell wall.
AB  - Recessive mutations at three loci cause the collapse of mature xylem cells in
      inflorescence stems of Arabidopsis. These irregular xylem (irx) mutations were
      identified by screening plants from a mutagenized population by microscopic
      examination of stem sections. The xylem cell defect was associated with an up to
      eightfold reduction in the total amount of cellulose in mature inflorescence
      stems. The amounts of cell wall-associated phenolics and polysaccharides were
      unaffected by the mutations. Examination of the cell walls by using electron
      microscopy demonstrated that the decreases in cellulose content of irx lines
      resulted in an alteration of the spatial organization of cell wall material. This
      suggests that a normal pattern of cellulose deposition may be required for
      assembly of lignin or polysaccharides. The reduced cellulose content of the stems
      also resulted in a decrease in stiffness of the stem material. This is consistent
      with the irregular xylem phenotype and suggests that the walls of irx plants are
      not resistant to compressive forces. Because lignin was implicated previously as
      a major factor in resistance to compressive forces, these results suggest either
      that cellulose has a direct role in providing resistance to compressive forces or
      that it is required for the development of normal lignin structure. The irx
      plants had a slight reduction in growth rate and stature but were otherwise
      normal in appearance. The mutations should be useful in facilitating the
      identification of factors that control the synthesis and deposition of cellulose
      and other cell wall components.

PMID- 9165748
TI  - Downregulation of ovule-specific MADS box genes from petunia results in
      maternally controlled defects in seed development.
AB  - A maternally determined seed defect has been obtained by downregulation of the
      petunia MADS box genes Floral Binding Protein 7 (FBP7) and FBP11. These genes
      have been previously shown to play central roles in the determination of ovule
      identity. Aberrant development of the seed coat and consequent degeneration of
      the endosperm have been observed in transgenic plants in which these two genes
      are downregulated by cosuppression. Analysis of the expression pattern of FBP7
      and FBP11 and genetic analysis confirmed the maternal inheritance of the
      phenotype. The FBP7 promoter was cloned and fused to reporter genes. One of these
      reporter genes was the BARNASE gene for targeted cell ablation. Our results
      indicate that FBP7 promoter activity is restricted to the seed coat of developing
      seeds and that it is completely silent in the gametophytically derived tissues.
      The mutants used in this study provided a unique opportunity to investigate one
      of the poorly understood aspects of seed development: the interaction of embryo,
      endosperm, and maternal tissues.

PMID- 9165749
TI  - ALBINO3, an Arabidopsis nuclear gene essential for chloroplast differentiation,
      encodes a chloroplast protein that shows homology to proteins present in
      bacterial membranes and yeast mitochondria.
AB  - The albino3 (alb3) mutant of Arabidopsis forms white or light yellow cotyledons
      and leaves and when germinated on soil does not survive beyond the seedling
      stage. The chloroplasts of the mutant are abnormal, as determined by electron
      microscopy, and contain reduced levels of chlorophyll. However, the chloroplasts
      of alb3 mutants are sufficiently differentiated to enable the expression of two
      nuclear genes whose transcription requires the presence of chloroplasts. The ALB3
      gene was isolated by transposon tagging with the Activator/Dissociation
      transposable element system. ALB3 is a novel plant gene whose product shows
      homology to a bacterial membrane protein previously identified in five bacterial
      species and to a yeast protein, OXA1, and its human homolog. OXA1 is required in
      the mitochondria for proper assembly of the cytochrome oxidase complex. ALB3 does
      not have a function identical to OXA1 because mitochondrial cytochrome oxidase
      activity is not affected in the mutant, and immunogold labeling as well as
      chloroplast import experiments performed in vitro demonstrated that the ALB3
      protein is present in chloroplast membranes. ALB3 might have a function related
      to that of OXA1 and be involved in the assembly of a chloroplast enzyme complex.

PMID- 9165750
TI  - RED1 is necessary for phytochrome B-mediated red light-specific signal
      transduction in Arabidopsis.
AB  - Seedlings of a transgenic Arabidopsis line (ABO) that overexpresses phytochrome B
      (phyB) display enhanced deetiolation specifically in red light. To identify
      genetic loci necessary for phytochrome signal transduction in red light, we
      chemically mutagenized ABO seeds and screened M2 seedlings for revertants of the
      enhanced deetiolation response. One recessive, red light-specific extragenic
      revertant, designated red1, was isolated. The mutant phenotype was expressed in
      the original ABO background as well as in the nontransgenic Nossen (No-0)
      progenitor background. red1 is also deficient in several other aspects of red
      light-induced responses known to be mediated by phyB, such as inhibition of
      petiole elongation and the shade avoidance response. red1 was mapped to the
      bottom of chromosome 4 at a position distinct from all known photoreceptor loci.
      Together with complementation analysis, the data show that red1 is a novel
      photomorphogenic mutant. The evidence suggests that red1 represents a putative
      phytochrome signal transduction mutant potentially specific to the phyB pathway.

PMID- 9165751
TI  - Reduced naphthylphthalamic acid binding in the tir3 mutant of Arabidopsis is
      associated with a reduction in polar auxin transport and diverse morphological
      defects.
AB  - Polar auxin transport plays a key role in the regulation of plant growth and
      development. To identify genes involved in this process, we have developed a
      genetic procedure to screen for mutants of Arabidopsis that are altered in their
      response to auxin transport inhibitors. We recovered a total of 16 independent
      mutants that defined seven genes, called TRANSPORT INHIBITOR RESPONSE (TIR)
      genes. Recessive mutations in one of these genes, TIR3, result in altered
      responses to transport inhibitors, a reduction in polar auxin transport, and a
      variety of morphological defects that can be ascribed to changes in indole-3
      acetic acid distribution. Most dramatically, tir3 seedlings are strongly
      deficient in lateral root production, a process that is known to depend on polar
      auxin transport from the shoot into the root. In addition, tir3 plants display a
      reduction in apical dominance as well as decreased elongation of siliques,
      pedicels, roots, and the inflorescence. Biochemical studies indicate that tir3
      plants have a reduced number of N-1-naphthylphthalamic (NPA) binding sites,
      suggesting that the TIR3 gene is required for expression, localization, or
      stabilization of the NPA binding protein (NBP). Alternatively, the TIR3 gene may
      encode the NBP. Because the tir3 mutants have a substantial defect in NPA
      binding, their phenotype provides genetic evidence for a role for the NBP in
      plant growth and development.

PMID- 9165752
TI  - The Arabidopsis ABSCISIC ACID-INSENSITIVE2 (ABI2) and ABI1 genes encode
      homologous protein phosphatases 2C involved in abscisic acid signal transduction.
AB  - Abscisic acid (ABA) mediates seed maturation and adaptive responses to
      environmental stress. In Arabidopsis, the ABA-INSENSITIVE1 (ABI1) protein
      phosphatase 2C is required for proper ABA responsiveness both in seeds and in
      vegetative tissues. To determine whether the lack of recessive alleles at the
      corresponding locus could be explained by the existence of redundant genes, we
      initiated a search for ABI1 homologs. One such homolog turned out to be the ABI2
      locus, whose abi2-1 mutation was previously known to decrease ABA sensitivity.
      Whereas abi1-1 is (semi)dominant, abi2-1 has been described as recessive and
      maternally controlled at the germination stage. Unexpectedly, the sequence of the
      abi2-1 mutation showed that it converts Gly-168 to Asp, which is precisely the
      same amino acid substitution found in abi1-1 and at the coincidental position
      within the ABI1 phosphatase domain (Gly-180 to Asp). In vitro assays and
      functional complementation studies in yeast confirmed that the ABI2 protein is an
      active protein phosphatase 2C and that the abi2-1 mutation reduced phosphatase
      activity as well as affinity to Mg2+. Although a number of differences between
      the two mutants in adaptive responses to stress have been reported, quantitative
      comparisons of other major phenotypes showed that the effects of both abi1-1 and
      abi2-1 on these processes are nearly indistinguishable. Thus, the homologous ABI1
      and ABI2 phosphatases appear to assume partially redundant functions in ABA
      signaling, which may provide a mechanism to maintain informational homeostasis.

PMID- 9165753
TI  - A nuclear-encoded function essential for translation of the chloroplast psaB mRNA
      in chlamydomonas.
AB  - We report the analysis of a photosystem I-deficient mutant of Chlamydomonas
      reinhardtii, F15, that contains a mutation at the TAB1 (for translation of psaB
      mRNA) nuclear locus. Pulse labeling of chloroplast proteins revealed that the
      synthesis of the two photosystem I reaction center polypeptides PSAA and PSAB was
      undetectable in this mutant. The mRNA levels of these proteins were only
      moderately reduced, suggesting that the primary defect occurs at a step during or
      after translation. We constructed chimeric genes consisting of the psaA and psaB
      5' untranslated region (5' UTR) fused to the aminoglycoside adenyltransferase
      (aadA) coding sequence, which confers spectinomycin resistance. Insertion of
      these genes into the chloroplast genome through biolistic transformation and
      analysis of their expression in the TAB1 mutant nuclear background revealed that
      the psaB (but not the psaA) 5' UTR is the target of the wild-type TAB1 function.
      This suggests that TAB1 is required for the initiation of psaB mRNA translation.
      The dependence of PSAA synthesis or accumulation on PSAB synthesis is strongly
      suggested by the identification of a suppressor mutation within the psaB 5' UTR.
      The suppressor specifically restores the synthesis of both proteins in the
      presence of the tab1-F15 mutation. The location of the suppressor mutation within
      a putative base-paired region near the psaB initiation codon suggests a role for
      TAB1 in the activation of translation of the psaB mRNA.

PMID- 9165754
TI  - The conserved B3 domain of VIVIPAROUS1 has a cooperative DNA binding activity.
AB  - The biochemical activities that underlie the genetically defined activator and
      repressor functions of the VIVIPAROUS1 (VP1) protein have resisted in vitro
      analysis. Here, we show that a glutathione S-transferase (GST) fusion protein,
      including only the highly conserved B3 domain of VP1, has a highly cooperative,
      sequence-specific DNA binding activity. GST fusion proteins that include larger
      regions of the VP1 protein have very low activity, indicating that removal of the
      flanking protein sequences is necessary to elicit DNA binding in vitro. DNA
      competition and DNase I footprinting analyses show that B3 binds specifically to
      the Sph element involved in VP1 activation of the C1 gene, whereas binding to the
      G-box-type VP1-responsive element is of low affinity and is nonspecific.
      Footprint analysis of the C1 promoter revealed that sequences flanking the core
      TCCATGCAT motif of Sph also contribute to the recognition of the Sph element in
      its native context. The salient features of the in vitro GST-B3 DNA interaction
      are in good agreement with the protein and DNA sequence requirements defined by
      the functional analyses of VP1 and VP1-responsive elements in maize cells.

PMID- 9165756
TI  - Genetic engineering of a recombinant fusion possessing anti-tumor F(ab')2 and
      tumor necrosis factor.
AB  - The construction, synthesis and expression of a genetically engineered
      bifunctional antibody/cytokine fusion protein is described. In order to target
      alpha-tumor necrosis factor (TNF) to tumor cells, recombinant antibody techniques
      were used to construct an RM4/TNF fusion protein containing the chimeric anti
      tumor F(ab')2 (RM4) as well as the TNF moiety. The recombinant cDNA of human TNF
      was linked to the 3' end of the chimeric heavy-chain gene fragment (M4)
      containing the VH, the CH1 and the hinge region to form the fused heavy-chain
      gene fragment M4-TNF. Transfection of the M4-TNF gene fragment into a VKCK cell
      line producing the chimeric light-chain of the same antibody allowed the
      transfectant secreting the bifunctional fusion protein RM4/TNF. The RM4/TNF was
      purified by affinity chromatography. Our data showed that RM4/TNF retained the
      TAG72 antigen-binding reactivity as well as TNF activity as measured by ELISA,
      Western blotting, flow cytometry analysis, immunohistochemistry and cytotoxicity
      assays using the human colon cancer cell line LS174T. Therefore, the bifunctional
      fusion protein RM4/TNF may prove useful in targeting the biological effects of
      TNF to tumor cells, and in this way stimulate the immune destruction of tumor
      cells.

PMID- 9165757
TI  - Comparison of the properties of trypsin immobilized on 2 Celite derivatives.
AB  - Trypsin was immobilized on 2 Celite derivatives and the kinetic properties of
      trypsin immobilized on these derivatives were determined and compared. Celite was
      derivatized with organosilane to give aminopropyl-Celite (APC) and a portion of
      this derivative was then succinylated to give succinamidopropyl-Celite (SAPC).
      Trypsin was covalently immobilized on APC using glutaraldehyde to activate amino
      groups and on SAPC using water-soluble carbodiimide to activate surface carboxyl
      groups. Enzyme loadings were 13.9 and 17.8 mg ml-1 of beads on APC and SAPC,
      respectively. Using p-tosyl-L-arginine methyl ester as substrate, the catalyst
      specific activity, KMapp and kcat/KMapp were 17.8 U ml-1 of beads, 3.60 and 21.0
      mM-1 min-1, respectively, for trypsin-APC as compared with 24.5 U ml-1 of beads,
      3.77 and 20.3 mM-1 min-1, respectively, for trypsin-SAPC. With beta-lactoglobulin
      as substrate, KMapp and kcat/KMapp were 0.36 and 1.62 mM-1 min-1 for trypsin-APC
      and 0.54 and 1.39 mM-1 min-1 for trypsin-SAPC, respectively. The pH range for
      optimal activity was much larger for both immobilized forms as compared with the
      soluble enzyme. The optimal temperature ranges were 40-50 degrees C for trypsin
      APC and 50-60 degrees C for trypsin-SAPC. The two methods of immobilization on
      Celite gave biocataysts with similar kinetic properties but immobilization on
      SAPC yielded slightly higher loadings and higher specific activities.

PMID- 9165755
TI  - Salicylic acid activates a 48-kD MAP kinase in tobacco.
AB  - The involvement of phosphorylation/dephosphorylation in the salicylic acid (SA)
      signal transduction pathway leading to pathogenesis-related gene induction has
      previously been demonstrated using kinase and phosphatase inhibitors. Here, we
      show that in tobacco suspension cells, SA induced a rapid and transient
      activation of a 48-kD kinase that uses myelin basic protein as a substrate. This
      kinase is called the p48 SIP kinase (for SA-Induced Protein kinase). Biologically
      active analogs of SA, which induce pathogenesis-related genes and enhanced
      resistance, also activated this kinase, whereas inactive analogs did not.
      Phosphorylation of a tyrosine residue(s) in the SIP kinase was associated with
      its activation. The SIP kinase was purified to homogeneity from SA-treated
      tobacco suspension culture cells. The purified SIP kinase is strongly
      phosphorylated on a tyrosine residue(s), and treatment with either protein
      tyrosine or serine/threonine phosphatases abolished its activity. Using primers
      corresponding to the sequences of internal tryptic peptides, we cloned the SIP
      kinase gene. Analysis of the SIP kinase sequence indicates that it belongs to the
      MAP kinase family and that it is distinct from the other plant MAP kinases
      previously implicated in stress responses, suggesting that different members of
      the MAP kinase family are activated by different stresses.

PMID- 9165758
TI  - Fatty hydroxamic acid biosynthesis in aqueous medium in the presence of the
      lipase-acyltransferase from Candida parapsilosis.
AB  - The lipase-acyltransferase from Candida parapsilosis has been shown to catalyze
      fatty hydroxamic acid biosynthesis in a biphasic lipid/aqueous medium. The
      substrates of the reaction were an acyl donor (fatty acid or fatty acid methyl
      ester) and hydroxylamine. The transfer of acyl groups from a donor ester to
      hydroxylamine (aminolysis) was catalyzed preferentially to the reaction of free
      fatty acids. The highest synthesis activity was obtained in the presence of 1 M
      hydroxylamine at 45 degrees C and pH 6. This work confirmed the originality of
      the enzyme from Candida parapsilosis, which acts more like an acyltransferase
      than an hydrolase. This feature makes it an enzyme of choice for the direct
      bioconversion of oils in aqueous medium.

PMID- 9165759
TI  - Production of Aspergillus niger pectolytic enzymes by solid state bioprocessing
      of apple pomace.
AB  - The aim of this work was to develop a low cost process for apple pomace
      utilisation. Accordingly this production of pectynolitic enzymes based on solid
      state bioprocessing of this actual waste, was developed. Production of pectolytic
      enzymes of Aspergillus niger, pectinesterase and polygalacturonase as well as the
      activity of pectolytic enzymatic complex by solid state bioprocessing were
      studied. The results of preliminary substrate optimization, on open trays in
      laboratory scale experiments, were transferred to 15 1 horizontal solid state
      stirred tank reactor (HSS STR). In situ sterilization of solid substrate with
      periodical mixing was used. Secondary raw material, apple pomace the waste from
      food and agriculture industry combined with soya flour, wheat bran and simple
      mineral salts was utilised. Various substrate moistures were studied. Process
      parameters such as inoculation, influence of mixing, aeration, temperature and
      moisture content on pectolytic enzymes production were studied. Maximal amounts
      of 15 g kg-1 of solid medium of polygalacturonase, 200 mg kg-1 pectinesterase at
      activity up to 900 AJDA U ml-1 of enzyme mixture was obtained on average.

PMID- 9165760
TI  - Continuous cultivation start-up control--an experimental investigation.
AB  - A control strategy to avoid development of synchronous growth in carbohydrate
      limited Saccharomyces cerevisiae cultivations is proposed and experimentally
      investigated. The basic idea is to control the metabolic flux through the
      pathways by manipulating the substrate feed rate to keep the ethanol
      concentration at a low level. An adaptive and a fixed parameter controller were
      investigated experimentally. Both controllers were initialized at the target
      conditions for the continuous cultivation, where the uncontrolled process is
      known to be marginally stable. The latter fact renders it unfeasible to attempt
      open loop operation at the critical dilution rate. The adaptive controller turned
      out to be superior to the fixed parameter controller. The superiority of the
      adaptive controller is ascribed to its ability to identify the process under
      varying cell activity. The obtained experimental results demonstrate that the
      desired operating point is reproducibly obtainable. However, after prolonged
      operation under different types of disturbances the yeast seemed to adapt towards
      an increased respiratory activity for the same low level of ethanol in the
      medium.

PMID- 9165761
TI  - Purification and characterization of an invertase from Candida utilis: comparison
      with natural and recombinant yeast invertases.
AB  - A periplasmic invertase from the yeast Candida utilis was purified to homogeneity
      from cells fully derepressed for invertase synthesis. The enzyme was purified by
      successive Sephacryl S-300, and affinity chromatography and shown to be a dimeric
      glycoprotein composed of two identical monomer subunits with an apparent
      molecular mass of 150 kDa. After EndoH treatment, the deglycosylated protein
      showed an apparent molecular weight of 60 kDa. The apparent K(m) values for
      sucrose and raffinose were 11 and 150 mM, respectively, similar to those reported
      in Saccharomyces cerevisiae. The range of optimum temperature was 60-75 degrees
      C. The optimum pH was 5.5 and the enzyme was stable over pH range 3-6.

PMID- 9165763
TI  - [57th National Congress of the Italian Society of Cardiology. Rome, 10-13
      December 1996. Abstracts].

PMID- 9165762
TI  - Cloning and sequencing of an alpha-glucosidase gene from Aspergillus niger and
      its expression in A. nidulans.
AB  - We have cloned an extracellular alpha-glucosidase gene from Aspergillus niger
      with oligonucleotide probes synthesized on the basis of the determined peptide
      sequences. The nucleotide sequence revealed an open reading frame of 985 amino
      acids split with three introns, and the deduced amino acid sequence was nearly
      identical to that of the alpha-glucosidase previously determined. The cloned gene
      was introduced into Aspergillus nidulans, and its expression in the transformants
      was shown to be regulated by the carbon sources in the medium, suggesting that a
      common regulatory expression system is shared by these two species as is the case
      of other starch-degrading enzymes of Aspergillus species.

PMID- 9165764
TI  - 1997 Receptor and ion channel nomenclature supplement.

PMID- 9165766
TI  - Quality of life, hope, and uncertainty of cardiac patients and their spouses
      before coronary artery bypass surgery.
AB  - The relationships among quality of life, uncertainty, and hope for 21 patients
      and their spouses before bypass surgery were examined in this study. The
      instruments used included: Ferrans' and Powers' Quality of Life Index, Mishel's
      Uncertainty in Illness Scale, and the Herth Hope Index. Greater uncertainty was
      associated with lower quality of life and hope scores for patients and spouses.
      Spouses were more uncertain about the patients' cardiac disease and had higher
      quality of life scores than the patients. Female patients had more uncertainty
      about their disease. Patients with poor left ventricle function had lower quality
      of life. Implications for practice include the need to incorporate the spouse
      into the plan of care. Also, the presence of uncertainty in the waiting period
      for surgery for both patients and their spouses, and its negative association
      with quality of life, reinforces the importance of pre-admission intervention
      with this population.

PMID- 9165767
TI  - The role of the nurse with families of patients in ICU: the nurses' perspective.
AB  - Although nurses are often charged with the responsibility of helping families
      cope with the stress that results when a loved one is hospitalized in a critical
      care unit, there is little research investigating how critical care nurses
      perceive their role with families. The objectives of this study were to (a)
      describe critical care nurses' role expectations and perceived role performance
      with respect to patients' families, and (b) describe the relationship between
      nurses' role expectations and their perceived role performance. Forty-seven
      nurses were surveyed in this descriptive, correlational study. There was a
      moderately strong correlation (r = .60, p < .0001) between role expectations and
      role performance. However, family-focused interventions requiring less time and
      less intense communication skills were performed more often than those requiring
      more time and greater skill in communication. Thus, certain family needs may be
      met inconsistently due to varied perceptions among nurses regarding their
      responsibility to families. The findings are discussed in relation to concepts
      from role theory.

PMID- 9165769
TI  - Certification--we've come a long way, baby!

PMID- 9165768
TI  - What kind of evidence does qualitative research offer cardiovascular nurses?
AB  - In this article I have tried to present a brief overview of qualitative research
      and to suggest some of the ways in which it may be of use to practitioners.
      Traditionally, we have not included qualitative studies in our discussion of
      research utilization. I think this is an unfortunate omission. Qualitative
      studies have a great deal to offer the practitioner and there are ways in which
      she or he can make use of them without doing so prematurely and without bringing
      harm to the client or patient. The required ingredients are twofold. First, from
      the research side we need scientifically sound studies. Second, from the practice
      side we need curious and informed consumers-consumers who are willing to take new
      information into their practice repertoires and let it inform those repertoires.
      Simple ingredients ... hard to get the cake to rise sometimes, though.

PMID- 9165770
TI  - So--what's the fuss about outcomes and outcome evaluation?

PMID- 9165771
TI  - The 1996 Schering Lecture. An inquiry into the experience of oncology patients
      who leave biomedicine to use alternate therapies.
AB  - Minimal attention has been given to the experiences of oncology patients who
      abandon biomedicine to use alternate therapies. This presentation explores the
      abandonment experience. It also examines this group's emotions, perceived stress,
      and coping strategies through stress theory. Congruent with past research these
      patients tend to be younger, attain higher education, and are interested in
      changing their health regimens. Analysis suggests that anger precipitates the
      abandonment and remains a residual force for these patients. While their
      expressed initial fear of cancer changes to hope with the use of an alternate
      therapy, the hope for cure seems to be carried to the extremes of illusion and
      denial of possible death. The study, conducted with a network sample, included
      individual interviews and a focus group. The value of this ethnography lies in
      the revelation that a) some similar experiences appear for patients who remain in
      biomedicine and patients who abandon biomedicine, and b) insights are provided
      for health professionals wishing to avoid situations of abandonment and wishing
      to facilitate estranged patients' return to biomedicine.

PMID- 9165772
TI  - Towards an inclusive cervical cancer screening strategy: approaches for reaching
      socioeconomically disadvantaged women.
AB  - Barriers to prevention and early detection of cancer among the socioeconomically
      disadvantaged are important areas for public health focus. A community coalition
      was established in North York, Ontario, to identify a suitable primary prevention
      initiative, cervical screening among young women of lower economic status. Two
      pilot communities were selected for the project. Community members, key
      informants and service providers participated in a series of individual and focus
      group meetings to identify barriers that impede cervical screening. The benefits
      and challenges of such a project will be importance to practitioners eager to
      work collaboratively on primary prevention initiatives. This article will be of
      interest to nurses wanting to foster a community coalition approach to program
      design, planning, implementation and evaluation. It will also assist nurses with
      utilizing needs-based assessment in their work. Although the findings relate to a
      population of women in a large urban centre, the results will be useful for
      nurses and other health professionals planning to engage in work related to
      cervical screening.

PMID- 9165773
TI  - Current trends in ventilation of the pediatric patient.
AB  - This article presents an overview of the varied modes of ventilation and
      supportive adjuncts for the pediatric patient. Ventilatory management has changed
      over the past few decades with the advent of high-frequency ventilation, pressure
      control-inverse ratio, pressure-regulated volume control, volume support,
      noninvasive bi-level pressure ventilation such as BiPAP, and the emergence of
      adjuncts to improve oxygenation such as surfactant, extracorporeal membrane
      oxygenation, nitric oxide, and total and partial liquid ventilation. Ventilatory
      management of pediatric patients mandates an armamentarium including guided
      imagery and the use of speech enhancers. A multidisciplinary team approach is
      essential.

PMID- 9165774
TI  - Outcomes manager: brain death criteria in the pediatric patient.

PMID- 9165777
TI  - Recognition and management of shock in the pediatric patient.
AB  - Shock continues to be a challenge for health care professionals because shock is
      not a single pathologic process but a complex series of interrelated events.
      After respiratory failure, shock is the second most common cause of death in
      children. The etiology of shock can be classified into three major categories:
      hypovolemic, cardiogenic, and distributive shock (septic shock). Despite the
      etiology of the shock state, if left untreated, the overwhelming response of the
      body to the inadequate perfusion is death. The key to successful management and
      treatment of shock is early recognition and rapid intervention.

PMID- 9165775
TI  - Management of the critically ill pediatric patient with acute renal failure.
AB  - Acute renal failure in the critically ill child can be a devastating and
      sometimes fatal event. Pediatric critical care nurses assume significant
      responsibility for early recognition, prevention, and treatment of children who
      develop acute renal failure. Knowledge of renal anatomy and physiology,
      developmental risk factors, nursing and medical management strategies, and renal
      replacement therapies is necessary for the delivery of competent care. This
      article explores the precipitating causes and complications of acute renal
      failure, prevention strategies, diagnosis and management, continuous renal
      replacement therapies, and the nurse's role in each. Furthermore, consideration
      is given to future treatments for acute renal failure.

PMID- 9165776
TI  - Pediatric traumatic brain injury.
AB  - Pediatric traumatic brain injury is a challenge to critical care practitioners.
      The prevention of secondary injury is key to improving morbidity and mortality
      outcomes. Interventions are targeted at maintaining adequate cerebral blood flow
      and minimizing oxygen consumption by the brain. The anticipation and prevention
      of systemic complications are also of vital importance. The impact that nursing
      judgment has on outcomes is notable. Pediatric traumatic brain injury is
      described, current treatments and issues are discussed, and an overview of
      outcomes related to morbidity are presented.

PMID- 9165778
TI  - Wound and skin care for the PICU.
AB  - Pediatric intensive care nurses are frequently challenged by caring for
      critically ill patients with wounds or the potential for skin breakdown. This
      article summarizes wound care guidelines, discusses nutritional support, and
      provides a tool for assessing the pediatric patient at risk for skin breakdown.

PMID- 9165779
TI  - Transport considerations for the critically ill child.
AB  - Transport of the critically ill child to and between hospitals has become a
      specialty field. Proper preparation and planning is critical on the part of the
      transferring party, the receiving facility, and the transport crew. Optimal
      patient outcome occurs when all parties involved understand each other and work
      together. Indications for transport, determination of transport mode, crew
      configuration of the transport team, necessary equipment, and physical
      examination including clinical interventions are key components of a successful
      transport. The following is a brief overview of these specific considerations
      involved when transporting the critically ill child.

PMID- 9165780
TI  - Thoracic trauma: a case review.

PMID- 9165781
TI  - Patient-focused care: what is it?
AB  - Patient-focused care is a philosophy incorporating a set of basic principles with
      which hospitals and other health care institutions organize and facilitate
      administration and delivery of the caring continuum. The pattern advocates
      fundamental change in basic operations and structuring of care delivery and
      projects considerable cost savings based on that change in utilization and
      organization of resources, staff, capital equipment, and the physical plant.
      Increased customer and professional staff satisfaction and creation of a learning
      organization that is ready to move with the fast-paced change inherent in today's
      health care delivery system are examples of projected benefits from
      implementation of this model.

PMID- 9165782
TI  - Multidisciplinary collaboration: conceptual development as a foundation for
      patient-focused care.
AB  - A participatory action research design using a combination of qualitative methods
      was used to induce a conceptual definition of multidisciplinary collaboration and
      to develop a measure of the concept among health care workers. Conclusions from
      the study include strategies to foster multidisciplinary collaboration among
      health care workers when health care delivery systems are being reengineered.

PMID- 9165783
TI  - Patient-focused care: anatomy of a failure.
AB  - The article describes the experience of implementing patient-focused care from a
      physician's perspective. Pitfalls that guarantee failure are presented, many of
      which are avoidable with early participation by all parties involved:
      administrators, nursing staff, physicians, and patients. Contamination of the
      process with downsizing needs, lack of support for staff in dealing with
      necessary change, loss of administrative commitment, and withholding of
      appropriated funds are among the key errors to be avoided.

PMID- 9165784
TI  - Issues in patient-focused care for the respiratory care practitioner.
AB  - Patient-focused care is the redesign of patient care so that personnel and
      resources are organized around the patient instead of departments. The reasons
      are many but usually involve cost reductions and improvement in the customer's
      perception of quality. Goals for this process include grouping patients by
      diagnosis, decentralizing services, and cross-training staff. The respiratory
      care practitioner is well prepared to fit into the patient-focused care model.
      Recent surveys show the impact of hospital restructuring on respiratory care to
      be rather positive.

PMID- 9165785
TI  - Program evaluation of a unit reengineered for patient-focused care.
AB  - A quasi-experimental research design was used to determine how successful a work
      redesign project based on the philosophy of patient-focused care was in meeting
      the established goals of increased multidisciplinary collaboration, improved
      satisfaction for health care clients and providers, decreased cost of care, and
      decreased length of stay. Results indicate that multidisciplinary collaboration
      decreased for all health care providers, especially the health care employee
      group that underwent a major role revision. Patient and health care provider
      satisfaction increased. The cost of care was budget neutral as a result of the
      shift of employee costs from centralized departments to units. Length of stay
      decreased.

PMID- 9165787
TI  - Caring in patient-focused care: the relationship of patients' perceptions of
      holistic nurse caring to their levels of anxiety.
AB  - Holistic nurse caring, also called patient-focused care, is a helping
      relationship between nurse and patient with the potential to enhance health and
      healing. Few studies, however, have examined the relationship of the process of
      nurse caring to patient outcomes. Hospitalized patients face many stressors that
      cause anxiety. It is known that abnormally high levels of anxiety can interfere
      with patients' recovery. The article reports a study of patients' perceptions of
      holistic nurse caring and the relationship of perceptions of caring to levels of
      anxiety. Patients perceived caring to be evident, and there was a significant
      relationship between these perceptions and patients' levels of anxiety.

PMID- 9165786
TI  - Patient-focused care in parish nursing.
AB  - Parish nurses are documenting their outcomes and, with them, instances of cases
      in which parish nurse interventions have potentially resulted in substantial cost
      savings to the federal government through averted Medicare expenses. Theoretical
      cost saving estimates implied in the first 600 visits exceeded $400,000. Half
      these estimates were related to scenarios where caregivers were sustained to
      facilitate ongoing home care. The other half were related to disregard of signs
      and symptoms warranting prompt attention. In either case, advocacy, referral,
      assistance finding, active listening, and supportive education efforts served to
      overcome major stumbling blocks to access for those elders and their caregivers
      who felt physically and emotionally isolated or overwhelmed by their situation.
      Facilitating access meant earlier, simpler, more cost-effective treatment of
      conditions that might otherwise have escalated to require complex care. In the
      1800 stories of record, half the concerns addressed by parish nurses were related
      to spiritual-psychosocial concerns (e.g., unresolved feelings, transitions,
      interpersonal tensions, caregiver stresses, and isolation). The other half were
      related to physical concerns (e.g., symptom disregard, illness self-care
      deficits, and struggles pertaining to functional safety or independence). Most
      significant, the former often contributed to the latter.

PMID- 9165788
TI  - Changing care patterns and registered nurse job satisfaction.
AB  - Job satisfaction for registered nurses continues to be a source of conflict and
      dissension within the health care delivery system. The acute shortage of
      registered nurses in previous decades has abated, but turnover has not.
      Reengineering, restructuring, and other new care delivery organizational patterns
      are being implemented as cost savings are sought. A cross-sectional descriptive
      survey of a nursing organization was conducted on the eve of implementation of a
      change in the care pattern at a large, acute care institution. Although results
      indicated a low level of job satisfaction overall, the nurses indicated that
      there was respect and value for nursing within the institution.

PMID- 9165789
TI  - Creating mosaics: the interrelationships of knowledge and context.
AB  - This qualitative interpretivist study analyzed the interrelationships between the
      knowledge gained through continuing nursing education programs and the context of
      nurses' clinical practice. The content of nursing continuing education programs
      offered 9-12 months previously was reviewed. Forty semi-structured, tape-recorded
      interviews were conducted with nurses from hospitals, nursing homes and home care
      agencies to determine their use of this new knowledge. Findings indicate that
      nurses used information from continuing education programs to construct a
      knowledge base and that this process was affected by the structural, human
      resources, political and symbolic frames of the context in which nurses practice.

PMID- 9165790
TI  - Surveying public health nurses' continuing education needs: collaboration of
      practice and academia.
AB  - In the last twenty years, entry level requirements for public health nursing have
      shifted to less and less educational preparation. Many agencies hire registered
      nurses with associate degree or diploma preparation who have no experience. The
      shift in entry level requirements has challenged public health nursing
      administrators and educators to examine continuing education needs to meet
      knowledge deficits among public health nurses. The study reported here presents
      findings from a national survey of 56 state and territorial health departments.
      The results clarify the continuing education needs and issues related to the
      educational gaps of public health nurses of the 1990s.

PMID- 9165791
TI  - An educational program to prepare acute care nurses for a transition to home
      health care nursing.
AB  - This article describes a continuing education program that prepares nurses with
      experience in acute care nursing for the transition to home health care nursing.
      The program is a 12-credit hour, two semester college program consisting of 8
      hours of theory and 4 hours of clinical practicum. A coalition of hospitals, home
      health agencies and an educational institution designed the program to maintain
      the economic welfare of nurses in an era of hospital layoffs, promote
      professional development and enhance the transition of nurses to home health
      nursing.

PMID- 9165792
TI  - Teaching psychosocial care to long-term care nursing assistants.
AB  - This article describes a training program that teaches nursing assistants to
      provide psychosocial care and manage problem behaviors, not just provide basic
      physical care, for elderly nursing home residents. Addressed are the variety of
      techniques that can be used to approach nursing assistant students as adult
      learners in any healthcare setting-long term, acute or home care.

PMID- 9165793
TI  - Attitudes and participation of registered nurses in continuing professional
      education in New South Wales, Australia.
AB  - This empirical study explored the attitudes and participation of registered
      nurses (RNs) in New South Wales (NSW), Australia in continuing professional
      education (CPE). A random sample of 500 RNs from across NSW was surveyed. Three
      hundred and forty seven (69%) responses were received. Findings showed a positive
      attitude toward CPE and a willingness to meet the necessary costs. However, the
      majority of RNs surveyed opposed the introduction of mandatory CPE, a finding
      that shows CPE may be an unnecessary measure in Australia. The findings suggest
      an already high participation rate in CPE as well as strategies alternative to
      mandatory CPE that would further enhance CPE participation.

PMID- 9165795
TI  - Sexuality in aging: implications for nursing facility staff.
AB  - Sexuality is an area that is frequently overlooked by staff who work with the
      elderly in nursing facilities. The nursing literature supports a need for
      education of nursing facility staff about sexual issues and concerns of facility
      residents. This article describes the effect of an educational intervention on
      one sample of facility staff and recommends strategies for the education and
      practice of staff members employed in nursing facilities.

PMID- 9165794
TI  - Clinical ladders: do they reflect levels of competence?
AB  - Staff nurses positioned within two discrete clinical ladder levels were surveyed
      for their responses to two components of clinical competence: job performance and
      problem-solving tactics. Although findings suggest that clinical ladders do not
      seem to provide clear delineation of competence levels, several interventions
      with staff nurses may increase clinical ladder viability: 1) opportunity to
      practice and utilize mixed and integrative problem-solving styles, 2) challenging
      work experiences, and 3) opportunity to mentor and be mentored.

PMID- 9165796
TI  - Patient stories: a way to enhance continuing education.
AB  - Using breast health and illness, this article reviews relevant research
      literature and compares it for congruency with patient stories. Inconsistencies
      and issues found are related to desired outcomes and decision-making. Patients
      may view cancer treatment as an unbroken continuum from pre-diagnosis to
      completion of treatment. While moving through the continuum, they interact with
      nursing professionals in several roles and locations. Strategic suggestions
      acknowledge the need to incorporate health professionals, patients and families
      in the continuing education activity. Nurses working in continuing education have
      the opportunity to improve care along the treatment continuum and reduce the
      distance between research and practice. Implications for nursing practice and
      continuing education are identified. Suggestions for enhancing continuing
      education related to this continuum are made.

PMID- 9165797
TI  - Influence of professional vs. personal role on pain assessment and use of
      opioids.
AB  - Previous surveys have revealed that patient characteristics such as behavior may
      influence nurses decisions about pain assessment and analgesic use. This survey
      suggested that the role assumed by the nurse, professional versus personal, also
      influences these decisions. The findings further suggested that continuing
      education aimed at improving pain management needs to include not only knowledge
      about pain assessment and safety in the use of opioid analgesics, but also
      teaching methods that increase empathy.

PMID- 9165798
TI  - Application of Nursing Interventions Classification (NIC) in a cardiovascular
      critical care unit.
AB  - The nursing profession is moving toward developing a standardized language.
      Benefits of such a language are outlined. Nursing Interventions Classification
      (NIC) (Iowa Intervention Project, 1992), a standardized language for nursing
      interventions, has been recently developed by the Iowa Intervention Project. This
      article describes how NIC was incorporated into a nursing care plan in a tertiary
      acute care facility. Teaching strategies, which include aspects of adult learning
      theory and motivational theory, are discussed. Utilization of creativity and
      variability in the planning and implementation of a unit based inservice program
      were the most beneficial strategies used.

PMID- 9165799
TI  - Computer generated slides--cheap!
AB  - Thirty-five millimeter slides can enhance the quality of presentations. They can
      present complex ideas and transmit information more clearly. They can engage the
      learner and add a touch of professionalism. However, the cost of professionally
      generated slides may be prohibitive for individuals working for smaller
      institutions with limited budgets. This article describes a method that can be
      used to produce high quality color slides with a fast turnaround time at a
      reasonable cost. Equipment needed is a computer with a graphics program and a
      suitably equipped camera.

PMID- 9165800
TI  - Mundanatories no more.
AB  - Mandated educational programs are often a source of dread for instructor and
      participant alike. The nurse educator, the Clinical Nurse Specialist for
      Intravenous (i.v.) Therapy and Nutritional Support, and the Clinical Program
      Manager for i.v. Therapy devised a self-paced program to validate the competence
      of Licensed Practical Nurses (LPNs) in caring for patients receiving i.v.
      therapy. The program consisted of learning stations which utilized a variety of
      formats to satisfy the objectives of the program. The LPN could see, hear about,
      read about, and ask questions related to i.v. therapy. Participants could take as
      much or as little time as was needed to review the stations. Documentation of
      competence was the completed quiz which became part of the LPN's personnel file.
      As an added incentive, the returned quiz was also used as an entry form to win
      door prizes. Compliance for the program was about 71%. Areas for improvement were
      identified. Feedback concerning the program from participants and planning team
      alike was very positive.

PMID- 9165801
TI  - A phenomenological interpretation of holistic nursing.
AB  - Phenomenology contributes to holistic nursing by interpreting the first-person
      encounter with the lived world. Holistic nursing care integrates
      biopsychosociological knowledge with the practical care that is the legacy of
      generations of practicing nurses. A practice, when interpreted
      phenomenologically, is a historically developed way of fostering human well
      being. Nursing is the practice of caring. Because nursing care concerns helping
      persons to live better in their world, it includes the moral, esthetic, and
      interpersonal aspects of care. These spiritual aspects are integrally enmeshed in
      holistic nursing. The spiritual in holistic nursing also designates the value
      dimension of meaning that gives life its worth and patients and nurses the
      courage to be. Interpreted phenomenologically, holistic nursing integrally
      relates scientific meaning with the meanings of nursing practice, the lived world
      of patients, and the meaning that gives patients and nurses the courage to seek
      well-being in a world altered by illness and debilitation.

PMID- 9165802
TI  - Guided Imagery. A psychoneuroimmunological intervention in holistic nursing
      practice.
AB  - Guided imagery is an independent nursing intervention that uses
      psychoneuroimmunology (PNI) principles to assist an individual in the management
      of distressing symptoms. The purpose of this article is to discuss the use of
      guided imagery in holistic nursing practice. The concepts of PNI are described
      and the basic steps of guided imagery are presented. PNI research and nursing
      research on guided imagery as an intervention are reviewed. The principles of
      guided imagery and PNI are applied to holistic nursing practice. Suggestions for
      future research methodologies, including psychological, neuroendocrine, and
      immunological measurements to evaluate the effectiveness of guided imagery, are
      offered. Rationale for using human immunodeficiency virus infection as a disease
      model to study the effectiveness of guided imagery is provided.

PMID- 9165803
TI  - Self-esteem and self-efficacy as predictors of success in smoking cessation.
AB  - The purpose of this study was to compare psychological, biophysical, and
      socioeconomic variables as predictors of success in smoking cessation adherence
      among adults who have participated in a smoking cessation program. The purposive
      sample (N = 75) was selected from participants of 10 smoking cessation programs
      in Texas who were measured for self-esteem and self-efficacy at the beginning of
      their program using the Rosenberg Self-Esteem Scale and Stanton's revised Self
      Efficacy for Smoking Cessation Questionnaire. Subjects self-reported their
      smoking/nonsmoking status and use/nonuse of the nicotine patch at the end of
      their program via postcards and at 3 months later through a phone interview with
      the researcher. Using discriminant analysis, the psychological variables
      correctly classified 75% of the subjects at the 3-month follow-up as smoking or
      nonsmoking (based on their preprogram scores of self-esteem and self-efficacy).
      With this sample, the biophysical and socioeconomic variables were insignificant
      in their ability to predict smoking cessation adherence.

PMID- 9165805
TI  - The state of research on the effects of therapeutic touch.
AB  - Therapeutic Touch is investigated using an integrative review of the literature.
      Using Ganong's (1987) methodology, the article explores the research question,
      What is the state of development of research regarding Therapeutic Touch? by
      analyzing primary research reports from 23 articles in 14 referred journals. The
      findings of the review indicate positive regard for the use of Therapeutic Touch.
      All research points to the need for further study in this area. Research methods
      used are satisfactory, but more rigorous methodologies would promote a more
      scientific contribution to the body of literature on Therapeutic Touch.

PMID- 9165804
TI  - Holistic health stress management program. Nursing student and client health
      outcomes.
AB  - This descriptive study examines the application of stress management techniques
      by nursing students to their clients (i.e., patients, family members, friends)
      within a model holistic stress management nursing course. Out of 90 students, 88
      completed a Client Teaching Relaxation Questionnaire during the course. Responses
      indicated a decrease in clients' perceived levels of discomfort following a
      stress reduction intervention (paired t = 18.7, df = 84, p < .0001). The students
      further reported that stress management skills were applicable to clients with a
      wide range of diagnoses in hospitals, homes, and other community settings.
      Imagery (52%) was documented as the predominant strategy taught to clients. Study
      results suggest that with teaching time allowed for self-mastery during the
      course, students can successfully apply these simple to complex stress management
      skills to many different clients, enhancing the caring aspect for both client and
      student. The course presented in this study provided students with essential
      foundational skills necessary to deal with client stress.

PMID- 9165806
TI  - The effectiveness of therapeutic touch for decreasing pain in elders with
      degenerative arthritis.
AB  - The purpose of this study was to determine if Therapeutic Touch (TT) decreased
      pain in elders with degenerative arthritis, compared with routine treatment and
      progressive muscle relaxation (PMR). Eighty-two noninstitutionalized subjects,
      age 55 or older, were randomly assigned to TT or PMR treatments. Subjects served
      as their own controls for 4 weeks and then received six treatments at 1-week
      intervals. Visual analogue scales (VAS) for pain intensity and distress were
      used. Significant differences from baseline to postsixth treatment were found
      within groups. TT decreased pain (t(46) = 7.60, p = < .001) and distress (t(44) =
      7.08, p = < .001). PMR decreased pain (t(36) = 6.58, p = .005) and distress
      (t(36) = 6.90, p = < .001). Differences in effectiveness existed between the TT
      and PMR groups; the pain and distress scores were lower in the PMR group. The
      differences approached significance for pain, F(2, 76) = 2.8, p = .06, and were
      significant for distress, F(2, 75) = 5.6, p = .005.

PMID- 9165807
TI  - Ingredients of an old and healthy life. A centenarian perspective.
AB  - This phenomenological study elicited centenarians' meanings of longevity and
      their perceptions of any common biological or psychosocial factors that they
      attributed to health and functioning. Twelve centenarians, ages 100 to 109, were
      interviewed. Common themes in their lived experiences included the meaning of
      long life, views of health, relationships with others, affirmation of worth,
      reasons for longevity, and God. Centenarians are long-term "survivors" with
      important lessons to share about high functioning, productive lives.

PMID- 9165808
TI  - Death of a newborn: healing the pain through Carper's patterns of knowing in
      nursing.
AB  - This article will explain how a nurse's holistic integration of empirical,
      esthetic, ethical and personal knowledge, as described by Carper's (1978)
      patterns of knowing in nursing", guided her teaching and nursing practice and
      helped a couple heal the pain of their newborn's death.

PMID- 9165809
TI  - The relationships of self-care agency and self-care actions to caregiver strain
      as perceived by female family caregivers of elderly parents.
AB  - The relationships of self-care agency and self-care actions to perceived
      caregiver strain among female family caregivers of elderly parents were examined
      in this descriptive correlational study. The length of time in the caregiver
      role, the quantity of multiple roles, and types of caregiving tasks performed by
      the caregiver were examined with the self-care variables to note their
      association with caregiver strain. This study was based on Orem's (1991)
      conceptual model. A convenience sample of 131 primary caregivers completed. The
      Burden Interview, Denyes Self Care Agency Instrument and Denyes Self Care
      Practice Instrument by mail survey. Significant findings show an inverse
      relationship between self-care agency and caregiver strain; self-care actions
      mediated relationships between household tasks, emotional support, and caregiver
      strain; the moderating effects of multiple roles on self-care actions increased
      caregiver strain, and the moderator effects of personal care tasks on self-care
      actions decreased caregiver strain. These findings suggest the need for nurses to
      educate caregivers to use effective self-care actions and to assess for factors
      that may influence caregivers and affect caregiving outcomes.

PMID- 9165810
TI  - An assessment of two upstate New York rural counties to determine unmet health
      needs of the Medicaid population.
AB  - Despite an influx of new providers in the primary care arena, there remains a
      documented need in rural areas for additional services. Using Health People 2000
      as an organizing framework, data from two upstate rural counties were analyzed to
      develop county profiles focusing on demographics, economics, morbidity,
      mortality, unemployment, and available health-related services. A survey based on
      these data was designed to examine reports of perceived health status and
      utilization of health care services. Results indicate a lack of providers and
      transportation, inaccessible office hours, unavailability of child/elder care,
      and excessive waiting time at the office or clinic as the greatest barriers
      perceived by rural Medicaid patients to receiving health care.

PMID- 9165811
TI  - Enhancing nurse mobility in Europe: a case for language skills.
AB  - The recognition of professional qualifications in all European Union (EU) member
      states for nurses is covered by both sectoral and general systems directives, yet
      in reality, few nurses take up their rights as European citizens to live and work
      in another EU country. One of the main reasons for this is a lack of linguistic
      skills. This article argues that the nursing profession should be taking a more
      active role in enabling nurses to move freely around Europe by encouraging
      language acquisition. It is argued that there are political, social, economic,
      professional and individual reasons why this should be so. The author gives a
      brief account of a pilot project which is currently under way to help improve
      (albeit in a small way) this situation. The project, which has been granted
      financial support of 100,000 ECU from the European Commission's new training
      programme, Leonardo da Vinci, will create a multimedia language pack in four
      languages aimed specifically at nurses.

PMID- 9165812
TI  - Learning the practice of nursing: views about preceptorship.
AB  - The provision of clinically based education for nursing students is an essential
      part of their learning needs. In this article, the opportunity to enhance
      clinically based learning by means of preceptors is discussed and investigated. A
      case study was conducted of one college of nursing after the introduction of the
      Preregistration Diploma of Higher Education in Nursing (Project 2000) course. The
      study involved preceptors (62), nursing students (15), ward managers (4), senior
      nurse managers (2) and nurse teachers (8). The investigation involved
      quantitative and qualitative approaches, data being gathered through
      questionnaires and interviews. The results indicate that preceptors included
      functions such as being a role model and supervision of learners' skills but not
      assessment as part of their role. These views were supported by students,
      teachers and managers. Knowledge of the clinical area and experience were
      reported to be preceptors' greatest assets for the role but lack of time to work
      with students was cited as the greatest barrier. Extra resources required were
      reported to be protected time for the student and preceptor to work together and
      further in-service education. The implications of these results for clinically
      based learning opportunities in the future are discussed.

PMID- 9165814
TI  - What's it all about, empathy?
AB  - This paper investigates the concept of empathy, a core element of all helping
      relationships. A discussion of its prevalence in the nursing literature is
      traced, before a discussion ensues as to whether it is a naturally acquired
      ability which develops with maturity, or whether it is a skill that can be taught
      and learnt. It is concluded that empathy remains a poorly defined,
      multidimensional concept which still remains not fully identified.

PMID- 9165813
TI  - Emergency, cardiac arrest! Can we teach the skills?
AB  - The European Resuscitation Council (ERC) has produced basic life support (BLS)
      and advanced life support (ALS) guidelines (1992) in an attempt to standardize
      the training and delivery of cardiopulmonary resuscitation (CPR). In response to
      this, the Avon and Gloucestershire College of Health, Glenside Centre (now
      University of the West of England), conducted a small survey, testing students'
      knowledge and skills in delivering CPR. Students were able to improve knowledge
      levels, but did not uniformly improve practical skills. Following this, the
      college formed a resuscitation team whose members coordinate CPR training in the
      curriculum, using uniform teaching packs which follow the ERC Guidelines (ERC
      1992a), and resuscitation equipment purchased by the college as the result of the
      research findings. In addition to maintaining uniform content, sessions are
      compulsory and students' CPR skills are tested, with a 70% competency level set
      as a pass. Student results and attendance are stored on a college database, along
      with tutor information regarding updating of CPR skills. To achieve these
      developments, the college has had to consider time allocation within the
      curriculum, training of tutors, funding of resources and funding of a compulsory
      training programme, which supports a ratio of one tutor to six students.
      Evaluations of the changes are favourable, as students' CPR skills and knowledge
      show obvious improvement and the students' general confidence and enthusiasm are
      enhanced.

PMID- 9165815
TI  - The 'F' factor: feminism forsaken?
AB  - This article discusses the link between feminist theory and midwifery practice.
      By incorporating concepts of feminist theory within this article, it is
      appropriate therefore that it should be written in the first person. I hope to
      illustrate why feminist theory is especially relevant to midwifery education and
      practice, and shall briefly highlight some of the feminist ideologies which may
      best fit the midwifery model. I also discuss a system of nursing education based
      upon feminist principles and values, devised by Hedin & Donovan in 1989, and its
      potential for adaptation to midwifery education.

PMID- 9165816
TI  - Nurse teachers and research.
AB  - This paper explores issues relating to the role of the nurse teacher in teaching
      and supporting research activity. Drawing on results from a survey of nurse
      teachers in four colleges of nursing in England (n = 126), nurse teachers'
      attitudes to research are explored and the implications in developing research in
      nurse education considered. This exploration builds on a previous review of nurse
      teachers' roles in research in one college of nursing (Clifford 1993) and focuses
      on the implications of the findings in the context of the move of nurse education
      into higher education.

PMID- 9165817
TI  - Nursing students' approaches to studying.
AB  - The Approaches to Study Inventory (ASI), developed by Entwistle & Ramsden (1983),
      was administered to all nursing students at an Australian university (response
      rate = 67%). The purpose was to find out whether ASI constructs also apply to
      nursing students and to see whether nursing students change in their study
      approaches in the course of their nursing education. The ASI was construct
      validated through factor analysis. While it was possible to reconstruct a
      majority of the subscales based on individual items, only the meaning and
      reproducing study orientations were supported. These two orientations also
      demonstrated satisfactory levels of internal consistency for group comparisons.
      The authors conclude that the ASI is a useful and robust instrument for use in
      nursing education with respect to the two main study orientations. Ideally,
      nursing education should successively pave the way for an increase in meaning
      orientation scores (deep learning) and a reduction in reproducing orientation
      scores (surface learning). However, in this study there was no change in study
      orientations from first to third year. The association between meaning
      orientation scores and academic performance was weak.

PMID- 9165818
TI  - Educational sources of stress in midwifery students.
AB  - This article presents the findings of a study that investigated educational
      sources of stress among student midwives working in England. The study set out to
      address the question, what are the clinical and educational experiences that can
      give rise to stress? Students were invited to complete a 45-item questionnaire
      which asked them to identify the extent to which a particular statement, in their
      experience, led to feelings of stress. There were four categories of response:
      'not at all', 'a little', 'much' and 'very much'. Responses from 199 students
      (127 preregistration and 72 preregistration (shortened)) were obtained. Factor
      analysis was used to determine the structure of the data set, and two factors
      emerged. Factor 1, accounting for 29.6% of variance, was labelled 'organizational
      and learning experience' sources of stress, while factor 2, accounting for 6.6%
      of variance, was labelled 'home and family' sources of stress. Further analysis
      on those items that were reported as having proportionately large numbers of
      students responding 'very much' was performed. Results from three items,
      'insufficient time to carry out assignments', "dealing with study vs.
      home/personal demands', and while on placements being exposed to "life and death
      situations', were found to be significantly different between preregistration and
      preregistration (shortened) students. These findings suggest that a wide variety
      of events cause students stress. While clinical sources of stress may be expected
      to exist, it must also be recognized that relationships with tutorial staff and
      aspects of the learning environment within colleges can also lead to stress.

PMID- 9165819
TI  - The problem of self-assessment in nurse education.
AB  - Nurse education is expected to fulfil two functions: the facilitation of
      individual personal development and professional selection. The need to produce
      competent nurses compromises the facilitation of personal development. This is
      reflected in the minor role assigned to self-assessment in preregistration nurse
      education. The problematic nature of self-assessment in nurse education is
      illustrated through a discussion of three issues: self-assessment and power, self
      assessment and stereotyping and self-assessment and context.

PMID- 9165820
TI  - Ideological influences on curriculum development in nurse education.
AB  - The development of curricula in nurse education cannot be viewed in isolation
      from the socio-political context within which it exists. Changes in the
      prevailing political ideology have impacted on the social life of individuals,
      and the reflection of this can be traced in the curricula of nursing courses over
      time. To ensure that courses meet the needs of both students and society, it is
      important for teachers to recognize the influence of the context within which
      such development takes place, and to understand the ideological underpinning of
      that which is being both taught and learnt. It is only with adequate
      understanding that challenges can be presented and change promoted when
      necessary.

PMID- 9165821
TI  - Developing the nurse teacher's role: the use of multiple focus groups to ensure
      grassroots involvement.
AB  - Strategies for teacher development must ultimately recognize that the only
      constant is likely to be change, and acknowledge the importance of social
      interaction as a component of organizational development. The process of
      development must therefore begin with the implementation of structures which
      enable an ongoing exploration of the role of the nurse teacher whilst at the same
      time creating an empowering, collectivist culture. This article describes a
      project undertaken by a number of nurse teachers to achieve this through the use
      of focus groups allied to the principles of action research. In total 10 groups
      were facilitated, involving 52 teachers. The data collected enabled the
      identification of dominant themes around which to cluster teacher activity and
      focus role development.

PMID- 9165822
TI  - Two studies of the new nursing education in Sweden: I. The place of gerontology
      and geriatrics. 2. Student characteristics and expectations.
AB  - In the autumn of 1993, a new system of nursing education started in Sweden. A
      questionnaire was sent to the presidents of all the colleges of nursing, health
      and the caring sciences, and questions were asked about the part played by
      gerontology and geriatrics in the new curricula. The responses showed a
      considerable variety in the amounts of theoretical and clinical education given
      at the colleges. During the first or second week of their education, the students
      admitted to three colleges in the Malaren area answered a questionnaire
      containing questions about their educational backgrounds, their working
      experiences in the health care system, why they chose nursing education, their
      ideas of the tasks that a registered nurse primarily carries out, and their
      preferences for work after graduation. The result shows a correlation between
      working experience and the reasons for studies. The students stated a preference
      for working in emergency care rather than in geriatric care after graduation from
      college.

PMID- 9165823
TI  - Can degree level practice be assessed?
AB  - An analogy can be made between assessment and research. Both assessment and
      research involve methods of inquiry into a situation, and the philosophical
      reasoning underpinning that inquiry could be the same. The basic beliefs of the
      assessor or researcher determine the methods of inquiry undertaken, and
      postmodern constructivism offers an alternative to the present traditional
      approaches to community nurse practice assessment. The author believes that
      emphasis should be placed on the assumption that knowledge is gained through the
      formation of personal and social constructions. These are derived from personal
      experience and social interaction and are therefore nebulous, exhibiting many
      'truths'. The assessor's own constructions of reality will influence the
      interpretation of situations, just as the students' will influence the
      interpretation of community nurse practice. The human complexity of community
      nurse practice assessment demands that this qualitative approach should be
      undertaken. The traditional quantitative, scientific inquiry, free from
      subjectivity, is not suitable for furthering the understanding of complex,
      changing, human behaviour. Nevertheless, validity and reliability, which are the
      hallmarks of quantitative research, traditionally have been the supposed
      indicators of accountability in community nurse assessment. The author argues
      that the link between accountability and traditional methods of community nurse
      assessment is tenuous, and the author proposes alternative methods of community
      nurse practice education and assessment using triangulation as a way of studying
      human behaviour from more than one standpoint. As Guba & Lincoln (1981) suggest,
      emphasis will be placed on credibility, acknowledging the importance of
      sensitivity, conceptual ability, creativity and insight.

PMID- 9165824
TI  - From apprenticeship to academia: an adult branch programme.
AB  - This paper describes aspects of the introduction an adult branch programme of a
      Diploma of Higher Education in Nursing course in a Scottish college of nursing
      and midwifery. It is argued that the Diploma of Higher Education in Nursing
      course represents a move from a so-called apprenticeship approach, that is the
      Scottish 1982 Modular Scheme of General Training, to a so-called academic
      approach under the auspices of the Project 2000 proposals which have been
      described as the most major development in the preparation of nurses in the UK
      for many years (UKCC 1986). This paper will discuss the challenges and
      difficulties encountered when designing the theoretical aspects of the course
      with respect to the nursing component. The implications of some of the major
      changes within the scheme of preparation for the clinical areas where the
      students gain experience will also be discussed. It will be suggested that
      practice supervision, a development of apprenticeship, is the way ahead.

PMID- 9165825
TI  - "What do nurses really do?".

PMID- 9165826
TI  - Reducing epidural catheter infections. Proven techniques to keep your patient
      safe.

PMID- 9165827
TI  - Nursing organizations on the Net.

PMID- 9165828
TI  - Using dry heat to promote healing.

PMID- 9165829
TI  - Taking care of PICCs.

PMID- 9165830
TI  - . . . About glove powder.

PMID- 9165831
TI  - Actionstat.

PMID- 9165832
TI  - Organ transplants. Tackling the tough ethical questions.

PMID- 9165833
TI  - Atrial flutter.

PMID- 9165834
TI  - Only a father.

PMID- 9165835
TI  - Comforting touch. Using topical skin preparations.

PMID- 9165836
TI  - Caring for patients with osteoporosis.

PMID- 9165837
TI  - Bringing acute abdomen into focus.
AB  - When you care for a patient with acute abdominal pain, you can't waste time-his
      life could depend on fast assessment and treatment. Follow this systematic
      approach to zero in on the diagnosis and intervene appropriately.

PMID- 9165838
TI  - Turning points that change careers.
AB  - Without warning, you care for a patient or deal with an event and the way you
      nurse ... maybe even the way you live ... is changed for good. These turning
      points are touchstones in a nursing career. Here are a few of these powerful
      stories. What are yours?

PMID- 9165839
TI  - Hospital bed side rails. Preventing entrapment.

PMID- 9165840
TI  - Preserving Dan's dignity.

PMID- 9165841
TI  - Delegating to unlicensed assistive personnel.

PMID- 9165842
TI  - Reaching out to Ali.

PMID- 9165844
TI  - Some interesting issues for nurses about that grey area of gifts.

PMID- 9165843
TI  - Presentation skills. Learning unit 070.
AB  - This unit forms the first part of the 1997 Clinical Practice and Management
      Awards (see back page). Anyone who has attended a conference, listened to a talk
      or heard evidence being presented will know just how important good presentation
      is. If speakers cannot hold the audience's attention, the message they are trying
      to convey will fail to be heard, however important it is. Good presentation
      skills can be developed by everybody using some simple techniques and plenty of
      practice.

PMID- 9165845
TI  - Something for everyone?

PMID- 9165846
TI  - Power failure.

PMID- 9165847
TI  - The key to drug security.

PMID- 9165848
TI  - The real enemy.

PMID- 9165849
TI  - Late blooming.

PMID- 9165850
TI  - A very peculiar practice nurse.

PMID- 9165851
TI  - Elect within.

PMID- 9165852
TI  - Citizens of Sunderland.

PMID- 9165853
TI  - Course for change.

PMID- 9165854
TI  - Midwives at the centre of care.

PMID- 9165855
TI  - Public health centre stage.

PMID- 9165856
TI  - Mental health network: putting theory into practice.

PMID- 9165857
TI  - The value of home support for cancer patients: a study.
AB  - The Community Oncology Project (COPE) was initiated to investigate home support
      from a trained oncology nurse at various stages of treatment. Patients who
      received home support during treatment responded better than those having visits
      after treatment had finished. The author discusses the patients' continuing need
      for home support and the issues of dependency that this raises.

PMID- 9165858
TI  - Nurses' perceptions of reflective practice.
AB  - Reflective practice has become an accepted part of nursing development. The
      authors of this article asked clinicians and managers in their trust how they
      thought reflective practice may be enhanced. The study has enabled the trust to
      develop reflective practice in a number of ways which may benefit clinicians,
      managers and patients.

PMID- 9165859
TI  - The arguments for and against circumcision.

PMID- 9165860
TI  - Enteral nutrition for children.

PMID- 9165861
TI  - Help the Aged's test case.

PMID- 9165862
TI  - Crossover skills save lives.

PMID- 9165863
TI  - Legal threat to home care.

PMID- 9165864
TI  - The fight against TB.

PMID- 9165865
TI  - Hierarchy harms health.

PMID- 9165866
TI  - One service.

PMID- 9165867
TI  - It could be you.

PMID- 9165868
TI  - Leaning on the boundaries. Interview by Daniel Allen.

PMID- 9165869
TI  - Health or profit?

PMID- 9165870
TI  - Evidence-based nursing: an introduction.
AB  - The Art & Science section of Nursing Standard this week is devoted to encouraging
      nurses to use evidence in their practice. As well as publishing some of the
      papers from the recent Evidence-Based Nursing conference in London, this report
      is based on the editorial which appeared in the pilot issue of Evidence-Based
      Nursing, a new journal jointly published by the BMJ Publishing Group and the RCN
      Publishing Company. It highlights the importance of using evidence in practice
      and explores the role of the new journal, which will be launched in November
      1997, in helping nurses to achieve this aim.

PMID- 9165871
TI  - Using evidence to demonstrate the value of nursing.
AB  - This article explores the position of nursing in relation to the evidence-based
      medicine (EBM) and clinical effectiveness (CE) initiatives. It argues that both
      activities are based on at least three implicit assumptions. By exploring these
      assumptions nurses can become more involved in evidence-based practice and
      clinical effectiveness activities.

PMID- 9165872
TI  - The nursing process--a method of collecting evidence?
AB  - This paper questions whether or not the nursing process can be a valid method of
      collecting evidence on which to base nursing care. The author asserts that it
      can, but only if the service user is involved in the entire process.

PMID- 9165873
TI  - Implementing research.

PMID- 9165874
TI  - Implications for nursing of the NHS R&D funding policy.
AB  - In this article, the author reviews the recommendations for NHS research and
      development funding being implemented as a result of the Culyer report (1994).
      The implications for nursing research are discussed and nurses are urged to make
      the most of the opportunities now being created.

PMID- 9165875
TI  - Childhood immunisation.

PMID- 9165876
TI  - Equal opportunity legislation.

PMID- 9165877
TI  - Hughes on health. Interview by Norah Casey.

PMID- 9165878
TI  - How long must nurses wait?

PMID- 9165879
TI  - Saving the NHS money.

PMID- 9165880
TI  - Genetic watch.

PMID- 9165881
TI  - The genetics revolution.

PMID- 9165882
TI  - Inheriting an ethical dilemma.

PMID- 9165883
TI  - Rewarding excellence.

PMID- 9165884
TI  - Solution for adhesions.

PMID- 9165885
TI  - Nurse-led services.
AB  - Continuing our series of reports based on work submitted to the King's Fund
      database, the following article describes the implementation of nurse-led
      services in a variety of clinical settings. The initiatives show the need for
      multidisciplinary and patient involvement in the various stages of development.

PMID- 9165886
TI  - How nurses perceive barriers to research implementation.
AB  - This article follows up a previous article on community nurses' perceived
      barriers to implementing research (Walsh 1997). Here the author examines the
      perceived barriers to research use among a sample of 63 hospital and 78 community
      nurses. The major barriers identified relate to the clinical setting and
      understanding research reports. The results have significant implications for
      managers of the service and educators who seek to promote research-based
      practice.

PMID- 9165887
TI  - Managing stress at work: an alternative approach.

PMID- 9165888
TI  - Teaching practical skills: a guide for preceptors.
AB  - Concern has been expressed that recently qualified nurses may be deficient in
      clinical skills. In this article the authors explore psychomotor skills learning
      and suggest strategies to support preceptors who have responsibility for
      developing such skills in students. The advice should prove helpful to clinical
      staff who are involved in teaching clinical skills to nursing students.

PMID- 9165890
TI  - Nowt so thick as nurses.

PMID- 9165889
TI  - Adult immunisation.

PMID- 9165891
TI  - Working with survivors.

PMID- 9165893
TI  - Satisfied in law.

PMID- 9165892
TI  - Value all NHS staff.

PMID- 9165894
TI  - Rope tricks.

PMID- 9165896
TI  - The conservative NHS vision. Interview by Norah Casey.

PMID- 9165895
TI  - Body talk.

PMID- 9165897
TI  - Evidence-based care through clinical practice.
AB  - This article describes how a working group examined ways to overcome difficulties
      with applying research findings to clinical practice. The group developed a ward
      based distance learning package to assist in developing staff skills and
      ultimately enhance patient health care. The package has implications for all
      registered nurses in all nursing contexts.

PMID- 9165898
TI  - A health clinic for people with learning disabilities.
AB  - The needs of people with a learning disability are not always met due to
      inequalities in healthcare provision. This study set out to explore the
      effectiveness of a 'pop in' clinic for these clients. It was found that the
      clinic was used by about one third of the population under study and a wide range
      of health problems were dealt with as a result. The author concludes that such a
      clinic is an effective method of reducing inequality and that specialist health
      visitors are in an ideal position to provide this type of service.

PMID- 9165899
TI  - How informal carers cope with terminal cancer.
AB  - This article reports selected findings from a qualitative study of informal
      carers. The study focused on people caring for relatives with terminal cancer and
      the findings reported here reflect how they cope with their relative's pain and
      medication. The author recommends that nurses involve carers in the decision
      making process to alleviate the stress carers experience and utilise their
      specialist knowledge of the patient.

PMID- 9165900
TI  - Cognitive bladder training in the community.
AB  - Following a study trip sponsored through a Cow & Gate scholarship award, the
      author of this article introduced a cognitive bladder training programme for
      children with daytime wetting problems. This article looks at how the programme
      was introduced and describes the components of the programme including
      educational tools, motivation and bio-feedback. As a result of the programme
      district-wide, multidisciplinary management guidelines have been introduced.

PMID- 9165901
TI  - The limitations of well men clinics for health education.
AB  - In seeking to change health-related behaviour, such as smoking and poor diet,
      well mer clinics may be asking too much of their clients. This article explores
      the conflict between male socialisation and health education against a background
      of male mortality and morbidity. To achieve health gain for men, the author
      suggests a shift in emphasis is required from individual behavioural factors to
      wider socio-structural change.

PMID- 9165902
TI  - Clinical aspects of schizophrenia.

PMID- 9165903
TI  - Choice is the word of the moment.

PMID- 9165905
TI  - A proud record.

PMID- 9165904
TI  - Elder abuse.

PMID- 9165906
TI  - Tinkering is not enough.

PMID- 9165907
TI  - No cause for effect.

PMID- 9165908
TI  - Speaking out.

PMID- 9165909
TI  - The double-glazed ceiling.

PMID- 9165910
TI  - Moved to tears.

PMID- 9165911
TI  - Big ears go to work.

PMID- 9165912
TI  - Help is at hand.

PMID- 9165913
TI  - Consulting room.

PMID- 9165914
TI  - Holistic health. Journey to the centre. Interview by Jane Salvage.

PMID- 9165915
TI  - Holistic health. Free the spirit.

PMID- 9165916
TI  - Ways and means.

PMID- 9165917
TI  - Client and counsellor. Interview by Eileen Fursland.

PMID- 9165918
TI  - Counting the cost of a car.

PMID- 9165919
TI  - Organising for the future.

PMID- 9165920
TI  - No butts.

PMID- 9165921
TI  - Learning to understand a patient's silence.
AB  - Nurses often feel uncomfortable with silence in their interactions with patients.
      This article explores a variety of meanings of silence and the different
      interpretations of silence within different cultures. Some therapeutic uses and
      responses to silence are then explored.

PMID- 9165922
TI  - Patients' views of nurse prescribing.
AB  - In 1994 the law was changed to allow nurses to prescribe from a limited
      formulary. The Department of Health commissioned research to evaluate nurse
      prescribing in eight pilot sites in England. This article presents part of this
      research. In particular, it examines how patients perceived the role of nurses
      and health visitors as prescribers. The study involved interviewing patients seen
      by community nurses before and after the introduction of nurse prescribing. The
      advantages patients identified coincided with the anticipated benefits, while the
      disadvantages that had been anticipated before the study were not confirmed.
      Patients were positive about nurses as prescribers and in some instances
      preferred nurses to doctors.

PMID- 9165923
TI  - Over-use of neuroleptics in nursing homes.
AB  - This article looks at the over-use of major tranquillisers in nursing homes. The
      problem of side-effects is discussed and solutions offered.

PMID- 9165924
TI  - An audit of catheter specimen testing practices in the ICU.
AB  - This article shows how the use of clinical audit in an intensive care unit
      resulted in a change of practice and cost savings. The rationale, method and
      results are described and then discussed.

PMID- 9165926
TI  - Community violence: its impact on the development of children and implications
      for nursing practice.
AB  - An alarming increase in the prevalence of violent crime in the United States has
      lead to the birth of a new subset of victims, children who witness acts of
      violence. Results of multiple studies suggest that chronic exposure to violence
      has a profound negative impact on children's cognitive, social, psychologic, and
      moral development. As primary care providers, pediatric nurses and nurse
      practitioners are well-positioned to assess these children for early signs of
      exposure to violence, offer guidance and counseling, and make referrals for
      proper treatment.

PMID- 9165925
TI  - On on-line decency and indecency.

PMID- 9165927
TI  - Nursing care of children of battered women.
AB  - Our understanding of children of battered women and their responses to violence
      is developing. Children's responses vary. Although some children manifest signs
      of distress, anxiety, and worry, others are able to overcome the deleterious
      effects of family violence with the help of inner resources and the support of
      caring people. Knowledge of these factors offer suggestions for nursing practice
      with battered women and their children. Nurses who care for battered women and
      their children must seek them out, listen, offer information, encouragement, and
      understanding.

PMID- 9165928
TI  - Community violence, children and youth: considerations for programs, policy, and
      nursing roles.
AB  - Nurses working with children and adolescents who witness or directly experience
      violence in the communities in which they live need to understand and recognize
      symptoms of mental-emotional distress that can result from these experiences. The
      nature of community violence is multifaceted. Therefore, sharing of knowledge and
      skills and collaboration between health care professionals from different
      disciplines can further theoretical understandings, enhance the effectiveness of
      prevention and intervention strategies, and inform development of, and advocacy
      for policies at local, state, and national levels to prevent, reduce, and
      intervene in community violence. These activities will offer challenges and
      opportunities to shape nurses' roles and nursing practice in future health care
      environments.

PMID- 9165930
TI  - Water fluoridation: time to reexamine the issue.
AB  - Water fluoridation was instituted as a public health measure more than 50 years
      ago to help limit dental caries. However, with the advent of fluoridated
      dentifrices, fluoridated infant formulas, and commercially prepared beverages
      with fluoridated water, the incidence of dental fluorosis is increasing. Health
      care professionals need to understand the history of water fluoridation, examine
      the benefits and complications of fluoride, and, if need be, take an informed
      political stance on an issue that is affecting large numbers among our pediatric
      population.

PMID- 9165929
TI  - Cystic fibrosis newborn screening: impact of early screening results on parenting
      stress.
AB  - Newborn screening for cystic fibrosis (CF) is currently available through dried
      blood analysis for immunoreactive trypsinogen (IRT). The possible parenting
      stress associated with false-positive results or the early diagnosis of an
      asymptomatic infant has yet to be systematically addressed. This exploratory
      study examined levels of parenting stress among mothers of these infants. Results
      indicated significantly less total parenting stress but greater defensiveness in
      responding among families of false-positive screened children relative to their
      healthy comparison families. Parents of children diagnosed with CF through
      newborn screening did not show significantly higher stress scores than their
      healthy or "traditionally-diagnosed" CF comparison families. They did however
      have high frequencies of "at-risk scores" warranting referral based on clinical
      cut-off levels for Total Parenting Stress scores (45%) and Child Demandingness
      subscale score (50%). As the possibility for expanding CF neonatal screening to
      other states is considered, the need for further exploration of psychosocial
      sequelae affecting parenting will be increasingly important.

PMID- 9165931
TI  - A pilot study on transplant eligibility criteria: valuing the stories in numbers.
AB  - The medical and nursing literature often seem divided between numerical,
      qualitative studies, and quantitative, narrative-based case histories. Rarely are
      the numbers generated by the first informed by the experiences and insights
      offered by the second type of study. This paper reports on a pilot study carried
      out at the Hospital for Sick Children, Toronto, on a methodology combining
      qualitative and quantitative data. Using the Analytic Hierarchy Process (AHP), a
      type of multicriterion decision making, focus groups were used to analyze survey
      based organ transplant eligibility criteria. Through this process, a portrait of
      the limits of that data was generated by staff members. Organ transplant
      eligibility was chosen because of its importance, and very public discussions
      arising from high profile cases in Canada and the United States.

PMID- 9165932
TI  - Commentary on Koch and Rowell article: changes in liver transplantation policy.

PMID- 9165934
TI  - Managed care fear not.
AB  - The evolution of managed care really began during World War II when a
      shipbuilding company, Kaiser, developed a health care plan for employees. The
      health care plan provided a continuum of care from prevention to acute care with
      its own providers at a low cost to employees. This was ingenious because other
      employers were paying insurance premiums without having any control over costs.

PMID- 9165933
TI  - Responses of preterm infants to unimodal and multimodal sensory intervention.
AB  - PURPOSE: To examine the immediate responses of preterm infants to two forms of
      unimodal [auditory only (A) and tactile only (T)] and two forms of multimodal
      sensory stimulation [auditory, tactile and visual (ATV); auditory, tactile,
      visual and vestibular (ATVV)]. METHOD: A convenience sample of 54 clinically
      stable preterm infants (33-34 postconceptional weeks) was randomly assigned to 1
      of 5 experimental groups [Control (C); (A); (T); (ATV); and (ATVV)]. Stimulation
      was applied for 15 minutes once daily for 4 consecutive days. RESULTS: Outcome
      measures included pulse (PR) and respiratory rate (RR), oxygen saturation,
      behavioral state (BS), and body temperature. Repeated measures ANOVA identified
      significant differences among the groups during intervention for PR (p < .001),
      RR (p = .01), and BS (p < .02). Infants receiving any intervention with a tactile
      component showed increasing arousal (change in BS), and increased PR and RR
      during stimulation. Group T infants had higher proportions of PR > 180 while
      Group ATVV had higher proportions of PR < 140 (p = .0001). Group ATVV showed
      increased alertness following stimulation (24%) in contrast to having the least
      alertness during stimulation (11%). CONCLUSIONS: Tactile stimulation alone may be
      too arousing for these infants while the addition of vestibular stimulation may
      modulate arousal and facilitate optimal arousal prior to feeding.

PMID- 9165935
TI  - Family-centered care and the anticipated death of a newborn.
AB  - Providing support for a family whose infant is expected to die requires planning
      and coordinated intervention by members of the health care team. From diagnosis
      until the death of the infant, the family's choices and needs must be integrated
      into an acceptable plan of care. The role of the health care team in this process
      includes four principal phases: planning for the baby's birth, preparing the
      siblings, caring for the baby, and supporting the family both at the time of the
      death and afterward. Specific strategies used by physicians, nurses, and child
      life specialists can encourage the family's full participation in the birth and
      death of the infant. A description of one family's experiences highlights
      implications for family-centered practice.

PMID- 9165936
TI  - Glue: the essence of leadership.

PMID- 9165938
TI  - Pediatric management problems. Febrile seizures.

PMID- 9165937
TI  - Promoting the overall development of infants and young children receiving home
      health services.
AB  - Because of medical conditions and/or as a result of prolonged hospitalization,
      many children receiving home health services demonstrate developmental delays.
      Home health personnel can play an important role in promoting a young child's
      developmental progress by being informed of the early intervention services
      available in the community, facilitating referral to needed developmental
      services, and incorporating developmentally appropriate strategies into their
      every day care.

PMID- 9165939
TI  - Postnatal pharmacologic prevention of intraventricular hemorrhage: meta-analysis
      of phenobarbital and indomethacin.

PMID- 9165940
TI  - Tuberculosis skin testing at the end of a century.
AB  - Tuberculosis remains a threat to children, particularly those in high-risk
      groups. This article reviews new screening protocols for tuberculosis, and
      appropriate methods for managing positive test results. An overview of new
      research related to tuberculin testing is presented.

PMID- 9165941
TI  - Vascular assessment in compression therapy.
AB  - Successful management of patients with leg ulcers depends on an understanding of
      the disease process. Accurate assessment is vital in identifying factors which
      will delay healing and increase the likelihood of ulcer recurrence. With such
      knowledge nurses can decide when compression therapy is appropriate.

PMID- 9165942
TI  - Compression bandaging for venous leg ulcers.
AB  - Effective compression heals leg ulcers and prevents their recurrence. Incorrect
      bandaging and poor technique are often features of leg ulcer management. A number
      of bandage systems are currently in use. Multi-layer systems appear to be more
      effective than single-layer systems.

PMID- 9165943
TI  - Compression hosiery.
AB  - Compression hosiery is used in the prevention of ulceration in vulnerable
      individuals. Compliance is achieved by good assessment, measurement, fitting and
      education.

PMID- 9165944
TI  - Change.

PMID- 9165945
TI  - AASCIN: the fire inside.

PMID- 9165946
TI  - Case study: high acuity to long-term.
AB  - High acuity nursing involves caring for clients who have potentially life
      threatening conditions. This care is described as required, due to a disruption
      in one or more principal organ systems. How high acuity care is differentiated
      from acute or long term care may be dependent on the client's initial overall
      condition and/or predicted outcome. The client discussed has sustained a spinal
      cord injury at the C5 level. This presentation will demonstrate how clients may
      continually pass through high acuity care circumstances, acute care, to
      ultimately a long term care situation. Description of this client in a case study
      format may result in a learning experience for practitioners concerned with the
      physiological and the psychosocial aspects of their clients who require high
      acuity, acute and/or long term care. Car or motorcycle accidents account for at
      least half of all spinal cord injuries. Most are injuries involving cervical
      segments number 5 and 6. Cord damage can ascend or descend as much as three
      levels above or below the injury, due to edema or cord compression post trauma
      (Woll, 1986). Accidents with severe damage to the spinal cord at the C5 level can
      result in quadriplegia. Injuries of this magnitude can be either complete or
      incomplete. Complete injuries cause a "... loss of all conscious motor and/or
      sensory function below the level of injury" while incomplete injury spares some
      function, motor and/or sensory (Zejdlik, 1992, p.66). The purpose of this article
      is to present a client case study as a model for practitioners who practice in
      high acuity, acute, and long term situations. Two nursing theories (self-care
      deficit and adaptation) will be used as a framework for the case study. An
      assessment of the client's physical findings, including history, physical
      examination, and psychosocial status will be described. Nursing diagnoses and
      nursing interventions for two specific clinical problems will be presented.
      Recommendations for future research, nursing care and/or referrals will be
      outlined.

PMID- 9165947
TI  - SCI recidivism and nursing home placement: an interdisciplinary approach.
AB  - Satisfactory placement of spinal cord injury (SCI) patients in community nursing
      homes presents a challenge for interdisciplinary team members and caregivers.
      Problems of recidivism exist. There is limited information about the presenting
      signs/symptoms of these patients in nursing homes or the economic impact of their
      frequent reentries into hospitals. To identify factors related to recidivism,
      nurses at the James A. Haley Veterans Hospital analyzed the demographic and
      clinical characteristics of readmissions from nursing homes to SCI units for two
      years. Analysis of risk factors aided in the identification of situations that
      predisposed patients to recidivism and served as a basis for program development.
      A Community Nursing Home Enrichment Program (CNHEP) was designed utilizing the
      interdisciplinary team. The CNHEP consisted of pre- and post-placement
      interventions designed to 1) prepare the veteran for a change in life style, 2)
      decrease frequency of rehospitalization and 3) improve placement outcomes.

PMID- 9165948
TI  - Paradigm for SCI nurse competency on adult-geriatric SCI rehabilitation unit.
AB  - This article is based upon an SCI Model Project, funded by the American
      Association of Spinal Cord Injury Nurses (AASCIN). The purpose of this project
      was to develop a model to validate theoretical and practical knowledge of
      Registered Nurses and Licensed Practical Nurses/Licensed Vocational Nurses in an
      SCI rehabilitation setting. The investigators were direct care providers in a 68
      bed SCI rehabilitation service at the James A. Haley Veterans Hospital in Tampa,
      Florida. The theoretical framework was based upon three aspects: Competency
      Validation, Theoretical Knowledge, and Practical Knowledge. Competency Validation
      was directed towards incorporating the elements of assessment, maintenance,
      demonstration, and improvement of competencies on an ongoing basis. Theoretical
      knowledge encompassed the cognitive and psychomotor aspects of SCI nursing, and
      Practical Knowledge highlighted the application of principles of caregiving. Two
      instruments were developed to harmonize theoretical and practical dimensions for
      competency validation: SCI Knowledge/Skill Appraisal (SKA) and Expertise in SCI
      Nursing Practice (ESNP). The purpose of this project was to design a model for
      validating theoretical and practical knowledge of Registered Nurses (RN's) and
      Licensed Practical Nurses/Licensed Vocational Nurses (LPN/LVN's) in an SCI
      rehabilitation setting. The investigators were direct care Licensed Practical
      Nurses/Licensed Vocational Nurses (LPN/LVN's) in an SCI rehabilitation setting.
      The investigators were direct care providers in a 68 bed spinal cord injury (SCI)
      rehabilitation service at the James A. Haley Veterans Hospital in Tampa, Florida.

PMID- 9165949
TI  - Nursing's headlong trajectory into the year 2000.

PMID- 9165950
TI  - Development and implementation of nursing consultation groups on a spinal cord
      injury unit.
AB  - Stress, time constraints, patient satisfaction, need for support, and cost
      containment became the impetus for a nursing consultation group on a spinal cord
      injury (SCI) unit. This unit is located in part of a center for rehabilitation in
      a large, tertiary care medical center. Staff on this unit care for a maximum of
      20 spinal cord injured individuals and their families. This article describes how
      the clinical nurse specialist (CNS) identified the need for such a group as well
      as the benefits, membership, structure, and types of nursing issues addressed.
      Pitfalls and how to avoid them are identified for those interested in developing
      similar consultation groups.

PMID- 9165951
TI  - Neuroprotection after spinal cord injury: state of the science.
AB  - Advances in the basic and clinical sciences are improving our ability to alter
      the course of injury that occurs after acute spinal cord trauma.
      Methylprednisolone, naloxone, GM-1 ganglioside, tirilazad mesylate and other
      agents have been or are currently being subjected to rigorous testing to
      determine their ability to protect compromised but viable cellular elements and
      improve the functional outcome of survivors. The authors summarize mechanisms of
      secondary (spinal cord) injury, discuss derivative pharmacotherapy, review
      clinical trial findings and raise issues related to future research. Special
      attention is directed to the Maryland studies of GM-1 ganglioside and the
      National Acute Spinal Cord Injury trials. Preliminary work regarding the roles of
      excitatory amino acids, endogenous opioid peptides, calcium channel blockers and
      nerve growth factors in secondary injury are also outlined.

PMID- 9165952
TI  - A biomechanical analysis of methods used for transferring totally dependent
      patients.
AB  - Lifting and transferring patients have been identified as frequent precipitating
      factors or causes of low back problems among nurses. This study systematically
      evaluated six different transfer methods (three manual and three mechanical)
      completed by two female nurses working as a team to transfer two totally
      dependent patients (heavy, 95 kg and light, 56 kg). The patient transfers were
      completed on a rehabilitation unit of a large university hospital. Each transfer
      was videotaped and the short (150 cm) and tall (178 cm) nurse each performed the
      lead and assist roles using all six methods for both patients for a total of 24
      transfers. A biomechanical software program referred to as the "3-Dimensional
      Static Strength Prediction Program (3DSSPPTM)" was used to model each patient
      transfer, and to compute the peak compressive force on the L5/S1 disc, as well as
      estimate the percent of the population with sufficient strength capability to
      transfer patients. The results of biomechanical analysis revealed that the low
      back compression forces exceeded the back compression design limit recommended by
      the National Institute for Occupational Safety and Health (NIOSH) (3400N). For
      the manual transfer methods peak compressive forces greater than 10,000 N were
      predicted, which far exceeded the NIOSH upper limit of 6400 N. When mechanical
      lift devices were used, the back compression forces were below the back
      compression design limits. This study reinforces the need to utilize a mechanical
      lift device when transferring totally dependent patients with only two nurses.

PMID- 9165953
TI  - Avoiding pitfalls in focus group research.

PMID- 9165954
TI  - On the dangers of monitoring. Or, primum non nocere revisited.

PMID- 9165955
TI  - Patient-controlled analgesia--who benefits?

PMID- 9165956
TI  - Critical incident reporting in the intensive care unit.
AB  - Critical incident reporting was introduced into the intensive care unit (ICU) as
      part of the development of a quality assurance programme within our department.
      Over a 3-year period 281 critical incidents were reported. Factors relating to
      causation, detection and prevention of critical incidents were sought. Detection
      of a critical incident in over 50% of cases resulted from direct observation of
      the patient while monitoring systems accounted for a further 27%. No
      physiological changes were observed in 54% of critical incidents. The most common
      incidents reported concerned airway management and invasive lines, tubes and
      drains. Human error was a factor in 55% of incidents while violations of standard
      practice contributed to 28%. Critical incident reporting was effective in
      revealing latent errors in our "system' and clarifying the role of human error in
      the generation of incidents. It has proven to be a useful technique to highlight
      problems previously undetected in our quality assurance programme. Improvements
      in quality of care following implementation of preventative strategies await
      further assessment.

PMID- 9165957
TI  - Single-breath inhalation induction of sevoflurane anaesthesia with and without
      nitrous oxide: a feasibility study in adults and comparison with an intravenous
      bolus of propofol.
AB  - The induction characteristics of sevoflurane in nitrous oxide and oxygen were
      compared with sevoflurane in oxygen alone and a propofol infusion. A vital
      capacity technique was used for the gaseous induction groups using a Mapleson A
      system and a 4-litre reservoir bag. Four end-points of anaesthesia were recorded:
      time to cessation of finger tapping, time to loss of eyelash reflex, time to jaw
      relaxation and time to regular settled breathing after laryngeal mask airway
      insertion. We also recorded sequential blood pressure and pulse rate, the
      incidence of adverse airway events and the acceptability of the induction
      technique. Propofol had a faster time to cessation of finger tapping (p < 0.05)
      and jaw relaxation (p < 0.01). These differences disappeared with the final
      induction stage and sevoflurane in nitrous oxide and oxygen had the faster time
      to regular settled breathing, though this did not reach statistical significance.
      Cardiovascular stability was good and comparable in all groups. There were few
      adverse airway events in any group and none caused oxygen saturation to fall
      below 96%. There was more excitation in the gaseous induction groups, though this
      did not interfere with induction. Patient satisfaction with induction was high.

PMID- 9165959
TI  - Is Hartmann's the solution?
AB  - As Hartmann's solution is commonly used by anaesthetists, we surveyed a group of
      Part III FRCA candidates to establish their knowledge of its constituents and the
      purpose and metabolism of the lactate in solution. Of the 82 candidates surveyed
      only three (4%) accurately recorded the electrolytes and their concentrations in
      Hartmann's solution. Lactate was stated to be a source of bicarbonate by 52 (63%)
      and a source of glucose by 17 (21%). The descriptions of lactate metabolism were
      largely imprecise, none was complete and 24 (29%) of candidates offered no
      explanation. The constituents of Hartmann's solution and their concentrations are
      designed to match those of plasma, reducing ion and fluid shifts postinfusion.
      The lactate in Hartmann's solution is metabolised by both oxidation and
      gluconeogenesis, predominantly in the liver, and bicarbonate is generated by both
      processes over 1-2 h.

PMID- 9165958
TI  - A comparison of midazolam with trimeprazine as an oral premedicant for children.
AB  - The effect of oral premedication was investigated in a double-blind, randomised
      trial in 85 children undergoing tonsillectomy and/or adenoidectomy. Orally
      administered midazolam 0.5 mg.kg-1 given 30 min pre-operatively was compared with
      trimeprazine 2 mg.kg-1 given 90 min pre-operatively and a placebo preparation.
      Compliance, sedation and ease of induction were assessed as were the duration and
      quality of recovery. Following premedication with midazolam none of the patients
      was anxious, crying or distressed on leaving the ward, compared with 2/28 in the
      trimeprazine group and 5/28 in the placebo group (p = 0.0007). More patients were
      calm and quiet on arrival in the anaesthetic room following midazolam than
      following trimeprazine, with both premedicant agents comparing favourably with
      placebo. There was no significant difference between the three groups in the time
      to recovery or the sedation score on discharge to the ward. Midazolam is a safe
      and effective oral premedicant for children.

PMID- 9165960
TI  - Dose-response relationship and effective time to satisfactory intubation
      conditions after rocuronium in children.
AB  - We assessed the neuromuscular blocking effects of, and intubation conditions
      following, rocuronium in 81 children aged 2-12 years. The study was conducted in
      three parts. Parts 1 and 2 were undertaken during anaesthesia with thiopentone,
      alfentanil and nitrous oxide. Neuromuscular blockade was evaluated by recording
      the force of contraction of the adductor pollicis in response to train-of-four
      stimulation at 2 Hz repeated every 10s. In Part 1 the potency of rocuronium was
      determined in 15 children using a single dose-response technique; in Part 2 onset
      and recovery times were determined in six children following rocuronium 0.6 mg.kg
      1. In Part 3 of the study, intubation conditions were assessed in five groups of
      12 children whose tracheas were intubated 30, 40, 50, 60 and 70s after rocuronium
      0.6 mg.kg-1 during anaesthesia with thiopentone. The times to satisfactory
      intubation conditions in 50% and 90% of children were determined by probit
      analysis. The effective doses of rocuronium to produce 50% and 95% twitch
      depression were 151 micrograms.kg-1 (95% confidence intervals: 129-173
      micrograms.kg-1) and 331 micrograms.kg-1 (95% confidence intervals: 249-543
      micrograms.kg-1), respectively. The mean times (SD) to 90% and 100% depression of
      control twitch following rocuronium 0.6 mg.kg-1 were 42 (11.8) s and 60.3 (19.3)
      s, respectively. The times to 5%, 25%, 75% and 90% recovery were 20.5 (3.1) min,
      26.1 (4.1) min, 35.1 (5.4) min, and 39.5 (6.4) min, respectively. Intubation
      conditions were satisfactory in 4/12 children at 30 s, 6/12 at 40 s, 8/12 at 50
      s, 11/12 at 60 s and 12/12 at 70 s. The times to satisfactory intubation
      conditions in 50% and 90% of children after rocuronium 0.6 mg.kg-1 were 38 s (95%
      confidence intervals: 30-44 s) and 61 s (95% confidence intervals: 55-70 s),
      respectively.

PMID- 9165961
TI  - Reduced cerebral vasomotor reactivity as an indicator of postoperative confusion.
AB  - Surgical intervention in elderly patients carries a high risk. A frequent problem
      with surgery in these patients is the occurrence of a temporary confusional
      state, which increases both the risk of postoperative complications and the need
      for intensive care. We hypothesised that, in part, temporary confusional state
      results from cerebral hypoxia occurring in response to blood pressure
      fluctuations during surgery. To assess whether disruption of autoregulation of
      cerebral blood vessels plays a role in temporary confusional state, we studied 31
      patients over 55 years of age, using the Doppler-carbon dioxide test. We
      determined whether vasomotor reactivity could be used diagnostically to identify
      those patients most likely to experience temporary confusional state. Blood flow
      velocity in the middle cerebral artery was detected using Doppler ultrasound, and
      hypercapnia was induced by breathing carbon dioxide until an end-tidal
      concentration of 8.0% by volume was reached. Vasomotor reactivity was calculated
      on the basis of the changes in blood flow velocity in response to the increase in
      carbon dioxide. Temporary confusional state was assessed using the Syndrome Short
      Test (Syndrom-Kurztest). We found that resting blood flow velocity was inversely
      related to age (p < 0.05). In addition, there was a significant inverse
      correlation between vasomotor reactivity and temporary confusional state (p <
      0.05). These data indicate that vasomotor reactivity, as measured by the Doppler
      carbon dioxide test, is a reliable tool to identify patients at risk for
      postoperative psychological disturbances.

PMID- 9165962
TI  - Public perceptions of postoperative pain and its relief.
AB  - In order to evaluate the general public's knowledge of postoperative pain and its
      management, a simple questionnaire was devised and sent out to five general
      practices in Scotland and Yorkshire. Questionnaires were completed voluntarily by
      529 people attending their general practitioner for reasons not related to
      surgery. Five hundred and fifteen completed questionnaires were analysed. Two
      hundred and thirty-nine (46.4%) responders had undergone previous major surgery
      whereas 267 (51.8%) had not. Attitudes to pain varied greatly and confirm the
      findings of other surveys that amongst the general public there is little or no
      understanding of the nature of postoperative pain or of the methods available to
      treat it. Despite the published literature, the public have a high degree of
      confidence in the ability of doctors and nurses to treat such pain. Widespread
      public and professional education is required before further improvements can be
      made to such a universal and basic clinical problem.

PMID- 9165963
TI  - A survey of postoperative nausea and vomiting.
AB  - A prospective interview-based survey on the incidence of postoperative nausea and
      vomiting in 1107 in-patients aged 4-86 years was conducted during a 3-month
      period. Nausea, emetic episodes and the need for anti-emetic medication were
      recorded for 24 h postoperatively. In the recovery room, the incidence of nausea
      and vomiting was 18% and 5%, respectively. Over the whole 24-h period, these
      figures were 52% and 25%, respectively; severe nausea was experienced by 8%. The
      highest incidence of emetic sequelae was observed in gynaecological patients; 52%
      of the 822 patients who received general anaesthesia and 38% of the 285 patients
      who received regional anaesthesia reported nausea. The most important predictive
      factors associated with an increased risk for nausea and vomiting were female
      gender, a previous history of postoperative sickness, a longer duration of
      surgery, nonsmoking and a history of motion sickness. Based on these five items,
      a simple score predicting the risk of nausea and vomiting was constructed with a
      moderately good discriminating power.

PMID- 9165964
TI  - Comparison of the Nellcor N-200 and N-3000 pulse oximeters during simulated
      postoperative activities.
AB  - Twenty-six healthy volunteers were monitored simultaneously with the Nellcor N
      200 and N-3000 pulse oximeters during nonhypoxaemic simulated postoperative
      activity. The overall number of registered events (hypoxaemic episodes or loss of
      signal) was fewer with the N-3000 than with the N-200 (8 vs. 32, p < 0.00005).
      Episodes of "desaturation' of > or = 5% from baseline were significantly fewer
      with the N-3000 than with the N-200 (5 vs. 19, p = 0.0001), and lowest values
      below 90% occurred nine times on the N-200, but were not seen with the N-3000 (p
      < 0.00005). Furthermore, episodes owing to loss of signal were significantly
      rarer with the N-3000 than with the N-200 (3 vs. 13, p = 0.001). The Nellcor N
      3000 oximeter may offer an advantage over the N-200 model when monitoring
      patients in the postoperative period.

PMID- 9165965
TI  - An evaluation of the SCOTI device.
AB  - The Sonomatic Confirmation of Tracheal Intubation (SCOTI, Penlon, UK) device was
      evaluated in the laboratory with cut and uncut tracheal tubes and in 50 adult
      patients who underwent tracheal and oesophageal intubation with uncut tracheal
      tubes. We could not configure the SCOTI reliably with cut tracheal tubes. In the
      clinical study using uncut tubes the SCOTI identified all oesophageal
      intubations, but was only able to identify 84% (95% CI: 73.8-94.2%) of tracheal
      intubations. We recommend caution in using this device and further independent
      evaluation to determine its reliability.

PMID- 9165966
TI  - Evaluation of thoracic epidural catheter position and migration using radio
      opaque catheters.
AB  - Migration of thoracic epidural radio-opaque catheters was evaluated in 25
      patients scheduled for thoracic surgery in the supine position (n = 5) or in the
      lateral position with lateral extension of the thoracic spine (n = 20). Chest
      radiography was performed daily for 3 days after operation. Eighty-nine per cent
      of catheter tips were visualised in the epidural space. The catheter tip position
      was unchanged in all patients operated upon in the supine position. In the group
      operated upon in the lateral position, the catheter tip retracted from day 1 to
      day 2 by an average of 0.69 cm (SD 1.08; p < 0.05); from day 2 to day 3 the
      average retraction was 0.35 cm (SD 0.67; p < 0.05).

PMID- 9165967
TI  - Patients' memories of events during general anaesthesia.
AB  - Awareness remains a serious complication of general anaesthesia with potential
      adverse psychological sequelae. Even during seemingly adequate general
      anaesthesia, implicit memory may be retained along with the ability to
      subconsciously process auditory stimuli. As a result behaviour may be modified
      and postoperative progress influenced. We shall discuss the structure of memory
      and the effects of increasing doses of general anaesthesia on cognitive
      processes. In addition methods of assessing the depth of anaesthesia will be
      reviewed.

PMID- 9165968
TI  - Anaesthetic disasters: handling the aftermath.

PMID- 9165969
TI  - Pain relief with oral cannabinoids in familial Mediterranean fever.
AB  - Cannabinoids have analgesic and, possibly, anti-inflammatory properties but their
      clinical use has been restricted by legislation. This is the first United Kingdom
      report of the controlled use of a standardised pharmaceutical preparation of
      cannabinoids in capsular form. The therapy was assessed in a patient with
      familial Mediterranean fever, who presented with chronic relapsing pain and
      inflammation of gastrointestinal origin. After determining a suitable analgesic
      dosage, a double-blind placebo-controlled cross-over trial was conducted using 50
      mg tetrahydrocannabinol daily in five doses in the active weeks and measuring
      effects on parameters of inflammation and pain. Although no anti-inflammatory
      effects of tetrahydrocannabinol were detected during the trial, a highly
      significant reduction (p < 0.001) in additional analgesic requirements was
      achieved. Future study designs can now incorporate prescribable forms of
      cannabinoids but the choice of previous cannabis users only as patients has
      clinical limitations. Cannabis naive patients would tolerate controlled
      investigations but may generate medicolegal problems.

PMID- 9165970
TI  - Haemodynamic effects of intravenous nimodipine following aneurysmal subarachnoid
      haemorrhage: implications for monitoring.
AB  - Nimodipine is widely used in patients with aneurysmal subarachnoid haemorrhage
      for the prevention and treatment of delayed ischaemic neurological deficits.
      Intravenous nimodipine has significant vasodilatory properties and may compromise
      the achievement of haemodynamic targets in patients who receive hypertensive
      hypervolaemic haemodilution therapy. We have studied 22 patients who received
      postoperative therapy with intravenous nimodipine and show that in a substantial
      minority (29%) hypotension was not reversed by simple volume loading or low doses
      of inotropes. Formal haemodynamic assessment in these patients showed widely
      varying haemodynamic variables, with differences in the need for inotropic and
      vasopressor therapy. We conclude that optimal haemodynamic management in this
      subgroup of patients will require the use of pulmonary artery catheterisation.

PMID- 9165971
TI  - Uterine rupture and epidural analgesia during trial of labour.
AB  - A case of complete uterine rupture during a trial of labour in which epidural
      analgesia was used is described. The pain of uterine rupture was not masked by
      the addition of fentanyl 25 micrograms to bupivacaine 0.25% 6 ml but was relieved
      by bupivacaine 0.375% 6 ml.

PMID- 9165972
TI  - Oxygenation of patients undergoing ophthalmic surgery under local anaesthesia.
AB  - The oxygenation of 30 patients undergoing elective ophthalmic surgery without
      sedation whilst breathing air was studied and was compared with two methods of
      oxygen supplementation. Arterial oxygen saturation, inspired and expired oxygen
      and carbon dioxide were analysed. The delivery of oxygen at 21.min-1 via nasal
      cannulae was shown to be superior to a method which directed oxygen from under
      the surgical drapes.

PMID- 9165974
TI  - Academic anaesthetists.

PMID- 9165973
TI  - Efficacy of ondansetron and metoclopramide for preventing postoperative emesis
      following strabismus surgery in children.
AB  - A double-blind, randomised, placebo-controlled trial was conducted to compare the
      efficacy of metoclopramide with the 5-HT3 antagonist, ondansetron, for the
      prevention of postoperative emesis in children undergoing elective strabismus
      surgery. None of the children received any premedication and a similar
      anaesthetic technique was used for all. Ondansetron 0.15 mg.kg-1, metoclopramide
      0.25 mg.kg-1 or saline placebo were administered following intravenous catheter
      placement. Episodes of emesis were recorded for the first 24 h for the intervals
      of 0-2, 2-6 and 6-24 h. The incidence of emesis in the first 24 h was observed to
      be 71.7% in the placebo group, 34.4% in the ondansetron group (p < 0.001) and
      61.4% in the metoclopramide group (p = NS). The severity of vomiting was less in
      the ondansetron group as compared with metoclopramide (p < 0.01) and placebo (p <
      0.001). Recovery room scores were comparable in all the groups. No serious side
      effects were observed in the ondansetron group. We conclude that prophylactic
      ondansetron is effective and superior to metoclopramide in the prevention of
      postoperative emesis in children following elective strabismus surgery.

PMID- 9165975
TI  - Uptake of desflurane.

PMID- 9165976
TI  - Academic anaesthetists.

PMID- 9165977
TI  - Mortality predicted by APACHE II. The effect of changes in physiological values
      on predicted hospital mortality.

PMID- 9165978
TI  - Apnoea testing in children.

PMID- 9165980
TI  - My anaesthetic machine's on fire.

PMID- 9165979
TI  - Monitoring failure and awareness hazard during prolonged surgery.

PMID- 9165981
TI  - Syringes and latex allergy.

PMID- 9165982
TI  - Identifying the caudal space--if it doesn't itch don't scratch.

PMID- 9165983
TI  - Breathing system terminology.

PMID- 9165984
TI  - Damage to a laryngeal mask during tonsillectomy.

PMID- 9165985
TI  - Anaesthesia for simple exodontia in the dental chair.

PMID- 9165986
TI  - Tunnelling of catheters.

PMID- 9165987
TI  - Sensory loss of the distal phalanx caused by pulse oximeter probe.

PMID- 9165988
TI  - The oldest patient?

PMID- 9165989
TI  - Back seat driving.

PMID- 9165990
TI  - A persistent problem with glass ampoules.

PMID- 9165991
TI  - PAF, a potent proinflammatory mediator, looking for its role in the pathogenesis
      of joint damage.

PMID- 9165993
TI  - Digital necrosis with Ogilvie's syndrome.

PMID- 9165992
TI  - Efficacy of non-steroidal anti-inflammatory drugs for low back pain: a systematic
      review of randomised clinical trials.
AB  - PURPOSE: To assess the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs)
      for low back pain. DATA SOURCES: Computer aided search of published randomised
      clinical trials and assessment of the methods of the studies. STUDY SELECTION: 26
      randomised clinical trials evaluating NSAIDs for low back pain were identified.
      DATA EXTRACTION: Score for quality (maximum = 100 points) of the methods based on
      four categories: study population; interventions; effect measurement; data
      presentation and analysis. Determination of success rate per study group and
      evaluation of different contrasts. Statistical pooling of placebo controlled
      trials in similar patient groups and using similar outcome measures. RESULTS: The
      methods scores of the trials ranged from 27 to 83 points. NSAIDs were compared
      with placebo treatment in 10 studies. The pooled odds ratio in four trials
      comparing NSAIDs with placebo after one week was 0.53 (95% confidence intervals
      0.32 to 0.89) using the fixed effect model, indicating a significant effect in
      favour of NSAIDs compared with placebo. In nine studies NSAIDs were compared with
      other (drug) therapies. Of these, only two studies reported better results of
      NSAIDs compared with paracetamol with and without dextropropoxyphene. In the
      other trials NSAIDs were not better than the reference treatment. In 11 studies
      different NSAIDs were compared, of which seven studies reported no differences in
      effect. CONCLUSIONS: There are flaws in the design of most studies. The pooled
      odds ratio must be interpreted with caution because the trials at issue,
      including the high quality trials, did not use identical outcome measures. The
      results of the 26 randomised trials that have been carried out to date, suggest
      that NSAIDs might be effective for short-term symptomatic relief in patients with
      uncomplicated low back pain, but are less effective or ineffective in patients
      with low back pain with sciatica and patients with sciatica with nerve root
      symptoms.

PMID- 9165994
TI  - Assessment of anti-endothelial cell antibodies in systemic sclerosis and
      Sjogren's syndrome.
AB  - OBJECTIVES: Anti-endothelial cell antibodies (AECA) have been detected in 19 to
      30% of patients with systemic sclerosis (SSc). The objective of this study was
      first to assess the role of a secondary Sjogren's syndrome (SS) in the occurrence
      of AECA in SSc. Secondly, we researched AECA in patients with primary SS, and
      investigated whether AECA were associated with vascular manifestations (Raynaud's
      phenomenon and vasculitis). METHODS: IgG-AECA were tested by an ELISA method in
      serum samples from 50 patients with SSc (16 of them had also a secondary SS), 50
      patients with primary SS, and 50 healthy controls. RESULTS: AECA levels were
      significantly higher in patients with SSc or primary SS than in healthy controls
      (p < 0.01 and p < 0.01, respectively). In patients with SSc, AECA values were
      significantly higher in patients with secondary SS (p < 10(-5)). In patients with
      primary SS, AECA levels were significantly higher in patients with Raynaud's
      phenomenon (p < 0.01), but not in patients with vasculitis. CONCLUSION: In
      patients with SSc, AECA are associated with a secondary SS. In patients with
      primary SS, AECA are associated with Raynaud's phenomenon, but not with
      vasculitis.

PMID- 9165995
TI  - Effect of resumption of second line drugs in patients with rheumatoid arthritis
      that flared up after treatment discontinuation.
AB  - OBJECTIVE: To assess the effect of resumption of second line drugs in patients
      with rheumatoid arthritis (RA) that flared after treatment discontinuation.
      METHODS: RA patients were studied whose RA flared up after discontinuation of
      second line treatment while being in remission and who received a second course
      of the drug. Disease activity parameters were prospectively assessed at the time
      of treatment discontinuation, during the period when the disease flared up, and
      three months thereafter. Furthermore the medical charts were reviewed at 12
      months after treatment resumption. RESULTS: There were 51 patients included in
      the study: 25 patients treated with antimalarial drugs, 10 with parenteral gold,
      four with d-penicillamine, eight with sulphasalazine, two with azathioprine, and
      two with methotrexate. Disease activity parameters showed significant improvement
      within three months of treatment resumption, but remained significantly worse
      when compared with that measured before treatment discontinuation. Within three
      months 47% of the patients fulfilled 20% response criteria. Disease activity 12
      months after treatment resumption was considered to be absent in 35%, mild in
      43%, and moderate or active in 22% of the patients. In four (8%) patients the
      resumed treatment was stopped because of lack of efficacy. Side effects were
      recorded in four patients, which did not result in treatment discontinuation.
      CONCLUSIONS: Resumption of second line drugs in RA patients whose disease flared
      up after discontinuation of treatment is effective and safe in most patients.
      Half of the patients responded within three months after resumption of the second
      line drug.

PMID- 9165996
TI  - Absence of peripheral blood T cell responses to "shared epitope' containing
      peptides in recent onset rheumatoid arthritis.
AB  - OBJECTIVES: To determine if peptides containing the 'shared epitope' sequence,
      QKRAA, from either endogenous, HLA-DR beta 1 (0401), or exogenous, Escherichia
      coli dnaJ, sources activate T cells in recent onset rheumatoid arthritis (RA).
      METHODS: Peripheral blood mononuclear cell (PBMC) proliferative and whole blood
      cytokine responses to shared epitope containing peptides from DR beta 1 (0401)
      and E coli dnaJ, to control peptides from DR beta 1 (0402) and hsp40 and to the
      recall antigen, tetanus toxoid, were tested in 20 untreated, recent onset RA
      subjects, 20 HLA, age, and sex matched healthy controls and 18 other subjects
      with inflammatory arthritis. PBMC proliferative responses to a second E coli dnaJ
      peptide (with the shared epitope at the N-terminus) and two peptides from type II
      collagen with high affinity for DR4(0401) were tested in a further 16 recent
      onset RA and 17 control subjects. RESULTS: PBMC proliferation and whole blood
      interferon gamma or interleukin 10 production in response to the shared epitope
      containing and control peptides were not different between the disease and
      control groups. On the other hand, compared with controls, RA subjects had
      significantly higher proliferation to a collagen II (aa 1307-1319) peptide, but
      significantly lower proliferation and interferon gamma production to tetanus
      toxoid. CONCLUSION: Recent onset RA subjects had no demonstrable increase in
      peripheral blood T cell reactivity to shared epitope containing peptides.
      However, a proportion had increased T cell reactivity to a peptide of similar
      length from a candidate RA autoantigen, collagen type II. Their impaired
      responses to tetanus are in keeping with evidence for general T cell
      hyporesponsiveness in RA.

PMID- 9165997
TI  - Mechanical and material properties of the subchondral bone plate from the femoral
      head of patients with osteoarthritis or osteoporosis.
AB  - OBJECTIVE: To determine the material properties of the subchondral bone plate in
      patients with osteoarthritis or osteoporosis. METHODS: Femoral heads were
      obtained after surgical removal from age and sex matched groups of patients with
      either osteoporosis (OP), after a fractured neck of femur, or osteoarthritis (OA)
      and compared with a normal group. The mechanical stiffness, density, and
      composition of the subchondral bone plate from sites selected to represent areas
      of heavy, intermittent, and light loading were measured. RESULTS: Overall, OP
      bone was the least stiff and dense, followed by OA bone; normal bone was stiffer
      and more dense (p < 0.05). Though OP bone contained less mineral, the organic and
      water contents were increased in proportion suggesting no change in the relative
      amount of organic matrix. OA bone was also hypomineralised (p < 0.05) but had
      different organic and water fractions suggesting a defect in the matrix. Site
      variation of most properties was small, though across all the groups the superior
      region was significantly stiffer than the inferior. CONCLUSION: This study shows
      that subchondral bone plate is less stiff than normal in both OP and OA and so
      cannot, by itself, explain the preserving of the overlying cartilage in OP while
      aiding its destruction in OA. However, the subchondral bone plate is only one
      part of the bony structure of the femoral head and changes in the cancellous bone
      need to be considered. The generalised changes in bone composition found in
      patients with OA support the hypothesis that the disease could involve the bone
      in the primary pathogenesis.

PMID- 9165998
TI  - Immobilisation causes longlasting matrix changes both in the immobilised and
      contralateral joint cartilage.
AB  - OBJECTIVE: The capacity of articular cartilage matrix to recover during 50 weeks
      of remobilisation after an atrophy caused by 11 weeks of immobilisation of the
      knee (stifle) joint in 90 degrees flexion starting at the age of 29 weeks, was
      studied in young beagle dogs. METHODS: Proteoglycan concentration (uronic acid)
      and synthesis ([35S]sulphate incorporation) were determined in six and three knee
      joint surface locations, respectively. Proteoglycans extracted from the
      cartilages were characterised by chemical determinations, gel filtration, and
      western blotting for chondroitin sulphate epitope 3B3. RESULTS: The proteoglycan
      concentrations that were reduced in all sample sites immediately after the
      immobilisation, remained 14-28% lower than controls after 50 weeks of
      remobilisation in the patella, the summit of medial femoral condyle, and the
      superior femoropatellar surface. In the contralateral joint, there was a 49%
      increase of proteoglycans in the inferior femoropatellar surface after
      remobilisation, while a 34% decrease was simultaneously noticed on the summit of
      the medial femoral condyle. Total proteoglycan synthesis was not significantly
      changed after immobilisation or 50 weeks' remobilisation in the treated or
      contralateral joint, compared with age matched controls. The chondroitin 6- to 4-
      sulphate ratio was reduced by immobilisation both in the radioactively labelled
      and the total tissue proteoglycans. In the remobilised joint, this ratio was
      restored in femur, while in tibia it remained at a level lower than controls.
      Neither immobilisation nor remobilisation induced epitopes recognised by the
      monoclonal antibody 3B3 on native (undigested) proteoglycans. CONCLUSION: These
      results show that the depletion of proteoglycans observed after 11 weeks of
      immobilisation was not completely restored in certain surface sites after 50
      weeks of remobilisation. The significant changes that developed in the
      contralateral joint during the remobilisation period give further support to the
      idea that a permanent alteration of matrix metabolism results even from a
      temporary modification of loading pattern in immature joints.

PMID- 9165999
TI  - Unusual but memorable. Pancreatic arthropthy.

PMID- 9166001
TI  - The relation between tender points and fibromyalgia symptom variables: evidence
      that fibromyalgia is not a discrete disorder in the clinic.
AB  - OBJECTIVE: To investigate the relation between measures of pain threshold and
      symptoms of distress to determine if fibromyalgia is a discrete construct/
      disorder in the clinic. METHODS: 627 patients seen at an outpatient rheumatology
      centre from 1993 to 1996 underwent tender point and dolorimetry examinations. All
      completed the assessment scales for fatigue, sleep disturbance, anxiety,
      depression, global severity, pain, functional disability, and a composite measure
      of distress constructed from scores of sleep disturbance, fatigue, anxiety,
      depression, and global severity-the rheumatology distress index (RDI). RESULTS:
      In regression analyses, the RDI was linearly related to the count of tender
      points (r2 = 0.30). Lesser associations were found between the RDI and
      dolorimetry measurements (r2 = 0.08). The RDI was more strongly correlated with
      the two measures of pain threshold than any of the individual fibromyalgia
      symptom variables. In partial correlation analyses, all of the information
      relating to symptom variables was contained in the tender point count, and
      dolorimetry was not independently related to symptoms. CONCLUSION: Tender points
      are linearly related to fibromyalgia variables and distress, and there is no
      discrete enhancement or perturbation of fibromyalgia or distress variables
      associated with very high levels of tender points. Although fibromyalgia is a
      recognisable clinical entity, there seems to be no rationale for treating
      fibromyalgia as a discrete disorder, and it would seem appropriate to consider
      the entire range of tenderness and distress in clinic patients as well as in
      research studies. The tender point count functions as a 'sedimentation rate' for
      distress, and is a better measure than the dolorimetry score.

PMID- 9166000
TI  - Characterisation of fibroblast-like cells in pannus lesions of patients with
      rheumatoid arthritis sharing properties of fibroblasts and chondrocytes.
AB  - OBJECTIVE: To better understand the characteristics of synoviocytes located in
      the rheumatoid arthritis (RA) pannus. METHODS: One cell line, termed PSC, was
      cloned from RA pannus lesions. Phenotypic analysis was done by contrast
      microscopy, indirect immunostaining, and safranin O staining. Transcription of
      several protooncogenes and matrix degrading enzymes was evaluated. The expression
      of mRNA for collagen II was detected by in situ hybridisation. The ability of
      anchorage independent growth was assessed by soft agarose culture. RESULTS: PSCs
      showed a high transcription of protooncogenes c-fos, c-myc and c-jun. They also
      expressed mRNA for matrix degrading enzymes, such as collagenase, cathepsin B,
      and cathepsin L. Anchorage independent growth assay demonstrated that PSCs formed
      colonies in soft agar culture. Phenotypic analysis showed that this fibroblast
      like PSC was stained intensely with anti-vimentin and anti-fibroblast antibody.
      In situ reverse transcriptase assay showed that the cell line expressed type II
      collagen mRNA. CONCLUSION: Alternative fibroblast-like cells were identified in
      the pannus lesion of RA sharing properties of fibroblasts and chondrocytes. These
      findings suggest that this fibroblast-like cell derived from pannus lesions may
      contribute to the destruction of the cartilage in RA.

PMID- 9166002
TI  - Anti-Ro/SS-A and anti-La/SS-B antibodies associated with cardiac involvement in
      childhood systemic lupus erythematosus.
AB  - OBJECTIVES: To determine the frequency and type of cardiac manifestations in
      children with systemic lupus erythematosus (SLE) and investigate whether cardiac
      involvement of SLE in children was associated with any autoantibody pattern.
      METHODS: Retrospective analysis of the medical records of all children with SLE
      (31 patients) seen between January 1984 and January 1994 by the paediatric
      rheumatology service at Children's Hospital in New Orleans. All patients
      satisfied the American College of Rheumatology criteria for the diagnosis of SLE.
      Paediatric SLE patients with cardiac manifestations based on echocardiogram were
      identified. Autoantibody tests at diagnosis were identified retrospectively by
      chart review, and the correlation between autoantibodies and cardiac involvement
      was analysed using the two tailed Fisher's exact test. RESULTS: Thirteen (42%) of
      31 SLE patients had cardiac manifestations of SLE. Seven (22%) had pericarditis
      without myocarditis, five (16%) had pericarditis and myocarditis, and one (3%)
      had myocarditis without pericarditis. Two patients (6%) with pericarditis had
      cardiac tamponade. Cardiac manifestations of SLE usually occurred at the time of
      diagnosis or within six months. Anti-Ro/SS-A antibodies were present in serum
      samples of nine of 11 (82%) patients with cardiac involvement and in five of 15
      (33%) without cardiac involvement (p = 0.02). Anti-La/SS-B antibodies were
      present in serum samples of six of 10 (60%) patients with cardiac involvement and
      two of 15 (13%) without cardiac involvement (p = 0.03). Anti-Sm and anti-RNP
      antibodies showed no correlation with the presence of cardiac disease.
      CONCLUSIONS: Cardiac involvement in our paediatric SLE population was frequently
      found and correlated significantly with the presence of anti-Ro/SS-A and anti
      La/SS-B antibodies.

PMID- 9166003
TI  - Sister chromatid exchange analysis in the lymphocytes of patients with ankylosing
      spondylitis.
AB  - OBJECTIVE: This study investigated whether any genomic change occurs in DNA level
      in ankylosing spondylitis (AS) by measuring sister chromatid exchange (SCE)
      frequency. METHODS: SCE frequency was detected on metaphase chromosomes obtained
      from peripheral blood lymphocyte cultures in 15 patients diagnosed as having AS.
      SCE values were also obtained from 15 healthy subjects as a control group. SCE
      frequencies were detected from metaphases obtained from standard blood cultures
      by using bromodeoxyuridine and staining by Giemsa. RESULTS: SCE frequencies of AS
      were statistically higher than those of the control group (p < 0.005).
      CONCLUSION: These results suggest that genetic factors may play a more important
      part than realised in the aetiology of AS.

PMID- 9166005
TI  - Insufficiency fracture of the sacrum revealing a pregnancy associated
      osteoporosis. First case report.

PMID- 9166004
TI  - Does lymphoma 'cure' rheumatoid arthritis?

PMID- 9166006
TI  - No endotoxin detected in plasma of patients with ankylosing spondylitis.

PMID- 9166007
TI  - Treatment with etidronate for men with idiopathic osteoporosis.

PMID- 9166008
TI  - Finger drop in a patient with rheumatoid arthritis.

PMID- 9166009
TI  - A traumatic deterioration in general surgeons access to emergency theatre.
AB  - An audit has been carried out of general surgical emergency theatre usage before
      and after the allocation of some of the emergency theatre time for trauma lists.
      The median delay between decision to operate and operation starting rose from 1
      hour 15 minutes to 2 hours 30 minutes. There was a fall in the number of
      operations carried out during the day (p < 0.001) and a corresponding increase in
      the number of procedures performed after midnight (p < 0.005). Emergency theatre
      usage provides advantages to patient and surgeon alike. However, by its nature it
      will not be fully occupied all of the time. There is always likely to be a
      temptation to use some of the "free time' for non-emergency cases. This results
      in the advantages of the emergency theatre being lost.

PMID- 9166010
TI  - Attitudes of patients to elective surgical admissions over Christmas and Easter.
AB  - It is often accepted by hospital staff that patients would prefer to be at home
      for the Christmas and Easter holiday periods. This is one of the reasons that
      elective surgery is reduced at these times. However there is very little evidence
      to prove whether this is true. To investigate this question 310 patients
      attending surgical or urological outpatients were given a self completion
      questionnaire asking them whether they would accept admission over these holidays
      if offered it. Overall 77 per cent of males and 76 per cent of females would
      accept admission over the Christmas period for elective surgery. This rises to 87
      per cent and 88 per cent over the Easter period. Older patients, widows or
      widowers, retired patients and patients with subjectively severe symptoms and
      conditions were groups that independently accepted such admissions more readily
      than others. Contrary to the perceived opinion in hospital staff, in this sample
      of surgical and urological patients most patients appear willing to accept
      admission for elective surgery over the Christmas or Easter holiday periods.

PMID- 9166011
TI  - SHOT surveillance programme.

PMID- 9166012
TI  - The retired surgeon: a potential teaching resource.

PMID- 9166013
TI  - Surgery in the Tropics--a waste of time?
AB  - Surgeons have a valuable contribution to make to the health care in a developing
      country, be it for a flying visit or for longer input. This article written from
      personal experience also suggests that the particular conditions which one has to
      work under lead to many new skills being learnt rapidly-surgical, management, and
      personal. I believe that such experience can only benefit the individual and such
      experience should therefore be encouraged during the formative years of a surgeon
      in training.

PMID- 9166014
TI  - Joseph Lister: pioneer of safe surgery.

PMID- 9166015
TI  - The origin of the word 'stent'.

PMID- 9166016
TI  - Jehovah's Witnesses.

PMID- 9166017
TI  - Paediatric HIV infection.

PMID- 9166018
TI  - Legislation and drug trials.

PMID- 9166019
TI  - Relationship between cardiopulmonary response to exercise and adiposity in
      survivors of childhood malignancy.
AB  - Many long term sequelae result from previous treatment for malignancy in
      childhood. However, little information exists on cardiopulmonary response and
      energy expenditure during exercise and their possible associations with excess
      body fat. Measurements of body composition and exercise capacity both at low
      intensity and maximal aerobic capacity were made on 56 long term survivors of
      childhood malignancy (35 survivors of acute lymphoblastic leukaemia (ALL) and 21
      survivors of other malignancies) and 32 siblings acting as controls. Female
      survivors of ALL had significantly greater mean (SD) body fat than survivors of
      other malignancies and siblings (32.5 (6.4)% v 24.3 (4.4)% and 26.3 (8.5)%
      respectively, p < 0.005). Energy expenditure at low intensity exercise was
      reduced in survivors of ALL, and negatively correlated with body fat after
      controlling for weight (partial r range -0.21 to -0.47, p < 0.05). Stroke volume,
      measured indirectly, was reduced and heart rate raised in ALL survivors at sub
      maximal exercise levels. Peak oxygen consumption was significantly reduced in
      girls and boys treated for ALL compared with siblings (30.5 v 41.3 ml/kg/min for
      girls, p < 0.05 and 39.9 v 47.6 ml/kg/min for boys, p < 0.05 respectively).
      Reduced exercise capacity may account in part for the excess adiposity observed
      in long term survivors of ALL.

PMID- 9166021
TI  - Predictors of hypoxaemia in hospital admissions with acute lower respiratory
      tract infection in a developing country.
AB  - Since oxygen has to be given to most children in developing countries on the
      basis of clinical signs without performing blood gas analyses, possible clinical
      predictors of hypoxaemia were studied. Sixty nine children between the ages of 2
      months and 5 years admitted to hospital with acute lower respiratory tract
      infection and an oxygen saturation (Sao2) < 90% were compared with 67 children
      matched for age and diagnosis from the same referral hospital with an Sao2 of 90%
      or above (control group 1), and 44 unreferred children admitted to a secondary
      care hospital with acute lower respiratory infection (control group 2). Using
      multiple logistic regression analysis, sleepiness, arousal, quality of cry,
      cyanosis, head nodding, decreased air entry, nasal flaring, and upper arm
      circumference were found to be independent predictors of hypoxaemia on comparison
      of the cases with control group 1. Using a simple model of cyanosis or head
      nodding or not crying, the sensitivity to predict hypoxaemia was 59%, and the
      specificity 94% and 93% compared to control groups 1 and 2, respectively; 80% of
      the children with an Sao2 < 80% were identified by the combination of these
      signs. Over half of the children with hypoxaemia could be identified with a
      combination of three signs: extreme respiratory distress, cyanosis, and severely
      compromised general status. Further prospective validation of this model with
      other datasets is warranted. No other signs improved the sensitivity without
      compromising specificity. If a higher sensitivity is required, pulse oximetry has
      to be used.

PMID- 9166020
TI  - Relation between insulin-like growth factor-I, body mass index, and clinical
      status in cystic fibrosis.
AB  - OBJECTIVES: Despite improved nutrition and intensive treatment, subjects with
      cystic fibrosis have difficulty in maintaining anabolism during intercurrent
      infections, which can result in reduced body mass index and impaired skeletal
      growth. Insulin-like growth factor-I (IGF-I) and its binding protein IGFBP3 are
      sensitive to changes in nutritional status. The aim of this study was to
      determine the relation between circulating concentrations of these peptides, body
      mass index, and clinical status in cystic fibrosis. METHODS: Serum concentrations
      of IGF-I and IGFBP3 were measured in 197 subjects (108 males, 89 females; mean
      age 9.69 years, range 0.41-17.9 years) and these data were analysed with respect
      to body mass index, pubertal stage, and clinical status as assessed by Shwachman
      score and forced expiratory volume in one second (FEV1). RESULTS: The mean height
      SD score of the children studied was -0.2 (SD 1.14) and the body mass index SD
      score -0.26 (1.4). The body mass index SD score declined with increasing age (r =
      -0.18) and paralleled changes in IGF-I concentrations, which also declined. The
      IGF-I SD score (calculated from control data) correlated with age (r = -0.53).
      The abnormalities were most obvious during late puberty, when IGF-I and IGFBP3
      concentrations were significantly reduced compared with those in control subjects
      matched for pubertal stage. The IGF-I SD score correlated with height SD score (r
      = 0.14) and the decline in IGF-I concentrations with the fall in body mass index
      SD score (r = 0.42). IGF-I SD scores also correlated with the Shwachman score (r
      = 0.33) and FEV1 (r = 0.17). CONCLUSIONS: The close relation between declining
      IGF-I and IGFBP3 concentrations and body mass index in patients with cystic
      fibrosis may simply reflect poor nutritional status and insulin hyposecretion.
      Nevertheless, IGF-I deficiency could also contribute towards the catabolism
      observed in these patients, and IGF-I SD scores correlated with other measures of
      clinical status such as the Shwachman score and FEV1.

PMID- 9166022
TI  - Respiratory status and allergy nine to 10 years after acute bronchiolitis.
AB  - In order to evaluate further the relationship between acute bronchiolitis in
      infancy and subsequent respiratory problems, children prospectively followed up
      from the time of their admission to hospital were reviewed along with a group of
      matched controls recruited at the previous five and a half year assessment. Sixty
      one index children and 47 controls took part. The groups were well matched for
      age, height, parental smoking, and social class. Although the prevalence of
      respiratory symptoms had fallen when related to the previous review, there
      remained an excess of coughing (48 and 17% in index and control children
      respectively; odds ratio 4.02) and wheezing (34 and 13% in index and control
      children respectively; odds ratio 3.59). Bronchodilator therapy was used by 33%
      of index children compared with 3% of controls. Lung function tests revealed no
      significant differences in the measurements of lung growth-for example, forced
      vital capacity, functional residual capacity, and total lung capacity-but the
      index children had significant reductions in measurements of airways obstruction
      for example, forced expiratory volume in one second, maximum expiratory flow at
      75, 50 and 25% of vital capacity, and airways resistance. Family history and
      personal skin tests showed no excess of atopy in the index group. This study
      supports the claim that the excess respiratory symptoms after acute bronchiolitis
      are not due to familial or personal susceptibility to atopy.

PMID- 9166023
TI  - Behaviour and physiological responses during prone and supine sleep in early
      infancy.
AB  - AIMS: To study the effect of prone and supine sleep on infant behaviour,
      peripheral skin temperature, and cardiorespiratory parameters to aid
      understanding of why prone sleeping is associated with an increased risk of
      sudden infant death syndrome. METHODS: Of 33 enrolled infants, 32 were studied at
      2.5 and 28 at 5 months of age. A computer aided multichannel system was used for
      polysomnographic recordings. Behaviour was charted separately. RESULTS: Prone REM
      (active) sleep was associated with lower frequencies of short arousals, body
      movements and sighs, and a shorter duration of apnoeas than supine REM sleep at
      both ages. At 2.5 months there were less frequent episodes of periodic breathing
      during prone sleep in non-REM (quiet) and REM sleep. Heart rate and peripheral
      skin temperature were higher in the prone position during both sleep states at
      both ages. CONCLUSIONS: The observation of decreased variation in behaviour and
      respiratory pattern, increased heart rate, and increased peripheral skin
      temperature during prone compared with supine sleep may indicate that young
      infants are less able to maintain adequate respiratory and metabolic homoeostasis
      during prone sleep.

PMID- 9166024
TI  - Inflammatory bowel disease and predisposition to osteopenia.
AB  - The prevalence of osteopenia in children with inflammatory bowel disease (IBD) is
      unknown. The effect of nutritional state, disease activity, and steroid therapy
      on bone mineral content (BMC) of whole body, lumbar spine, and left femoral neck
      measured by dual energy x ray absorptiometry in 32 children with IBD was assessed
      by comparison with 58 healthy local school children. Using the control data, a
      predicted BMC was calculated taking into account bone area, age, height, weight,
      and pubertal stage. The measured BMC in children with IBD was expressed as a
      percentage of this predicted value (% BMC). Mean (SD) % BMC was significantly
      reduced for the whole body and left femoral neck in the children with IBD (97.0
      (4.5)% and 93.1 (12.0)% respectively, p < 0.05). Of the children with IBD, 41%
      had a % BMC less than 1 SD below the mean for the whole body and 47% at the
      femoral neck. Reduction in % BMC was associated with steroid usage but not with
      the magnitude of steroid dose, disease activity, or biochemical markers of bone
      metabolism. In conclusion, osteopenia is relatively common in childhood IBD and
      may be partly related to the previous use of steroids.

PMID- 9166026
TI  - Respiratory morbidity from lymphocytic interstitial pneumonitis (LIP) in
      vertically acquired HIV infection.
AB  - The aim of the study was to define the respiratory morbidity caused by
      lymphocytic interstitial pneumonitis (LIP) in children with vertically acquired
      HIV infection. A retrospective case note review was performed on 95 children
      attending three London hospitals. Clinical and radiological evidence of LIP,
      acute lower respiratory tract infections, and chronic lung disease was obtained
      using a structured protocol. A diagnosis of LIP had been made in 33%, and an
      acute admission due to acute lower respiratory tract infection had occurred in
      42% of all children (despite 99% taking regular cotrimoxazole prophylaxis).
      Admission rates because of acute lower respiratory tract infection were
      significantly higher in the LIP group (0.38 admissions/child year) than in the
      non-LIP group (0.17 admissions/child year) (p = 0.0002). Encapsulated bacteria
      (Streptococcus pneumoniae, Haemophilus influenzae) were most frequently isolated.
      Improved methods of prevention of acute lower respiratory tract infection may
      help to reduce the severe respiratory morbidity seen in children with LIP and HIV
      infection.

PMID- 9166025
TI  - Malignancies in UK children with HIV infection acquired from mother to child
      transmission.
AB  - By April 1995, 302 cases of vertically acquired HIV infection had been reported
      through the British Paediatric Association Surveillance Unit. Over 50% of these
      children had developed an AIDS indicator disease, including nine malignancies
      (seven cases of non-Hodgkin's lymphoma (NHL) and two of Kaposi's sarcoma). There
      were two other malignancies that were not AIDS indicator diseases. In children
      less than 5 years of age the incidence of NHL was approximately 2500 times
      greater than expected in the UK child population. Three children presented with
      NHL as their AIDS indicator disease and four developed NHL at a median of 14
      (range 10-19) months after the initial diagnosis of AIDS. Six of the seven
      children died at a median of 6.5 (range 2-14) months after the diagnosis of NHL.
      The seventh child responded to treatment and is alive nearly four years later.
      Histology was available in five cases, of which four were of B cell and one of T
      cell origin. Epstein-Barr virus was detected in all three patients with NHL where
      it was sought; all had B cell lymphomas. Although comparatively rare,
      malignancies occur in children infected with HIV and may be the presenting
      illness. Paediatricians now need to consider HIV infection as a predisposing
      cause of childhood cancer, especially NHL.

PMID- 9166027
TI  - Field trial of graded care profile (GCP) scale: a new measure of care.
AB  - AIM: The graded care profile (GCP) scale was developed as a practical tool in
      response to the Children Act 1989 to provide a measure of care in four areas:
      physical, safety, love, and esteem, on a bipolar continuum. This field trial was
      to assess its user friendliness and inter-rater agreement. METHODS: 43 nursery
      children and 11 registered for neglect were each scored on this scale
      independently by two different raters (health visitor and nursery teacher or
      social worker). Their inter-rater agreement was assessed by weighted kappa and
      user friendliness by time taken for and completeness of scoring. RESULTS: An
      almost perfect level of agreement was achieved in physical care (kappa = 0.899;
      confidence interval (CI) = 0.850 to 0.948), safety (kappa = 0.894; CI = 0.854 to
      0.933), esteem (kappa = 0.877; CI = 0.808 to 0.946), and a substantial level in
      love (kappa = 0.785; CI = 0.720 to 0.849). Mean time taken for scoring was 20
      minutes (range 10 to 30); of 54 paired scales, area of safety was not scored only
      in three by one of the raters. CONCLUSIONS: This scale appeared user friendly and
      provided grading of care with high inter-rater agreement. Its use in practice
      could provide an opportunity for useful comparison with other means of assessment
      of care, studying outcomes of different care profiles, targeting intervention,
      and monitoring change.

PMID- 9166028
TI  - Season of birth as predictor of atopic manifestations.
AB  - The relation between month of birth, sensitisation, and manifestations of atopy
      was assessed in 209 children who were followed from birth to 12-15 years.
      Children born during the tree pollen season were less likely to develop allergic
      rhinoconjunctivitis, IgE antibodies to pollen, or a positive screening test for
      IgE antibodies (odds ratio 0.28, 0.41, 0.35, respectively) than children born
      during the rest of the year. The prevalence of IgE antibodies to food and animal
      dander at 9 months and to atopic disease was higher in children born in the
      autumn and winter, that is, September to February, compared to the spring and
      summer (egg 20% v 6%; milk 10% v 2%). Thus sensitisation to pollen and allergic
      rhinoconjunctivitis is least common in children born in the spring, while birth
      in September to February is associated with an increased incidence of
      sensitisation to food and of atopic disease.

PMID- 9166029
TI  - Non-infective colitis in infancy: evidence in favour of minor immunodeficiency in
      its pathogenesis.
AB  - Forty two infants below the age of 2 years presenting with chronic non-infective
      diarrhoea and shown to have histologically proved colitis were investigated over
      a five year period. Allergic colitis was the most common cause of colitis,
      accounting for 62% of the cases. Other colitides diagnosed included: non-specific
      colitis, autoimmune enterocolitis, and ulcerative colitis accounting for 10%
      each; severe combined immunodeficiency 7%, and Crohn's disease 3%. A positive
      family history and a personal history of atopy were obtained in 48% and 29% of
      the cases respectively. Serum immunoglobulin A, IgG2, and IgG4 were very low in
      over 50% of the entire cohort of infants with colitis; 66% of those with severe
      combined immunodeficiency, autoimmune enterocolitis, and ulcerative colitis (n =
      11) had low CD3 and CD4 T lymphocytes with an accompanying increase in CD8 in two
      thirds of those with severe combined immunodeficiency. T lymphocytes were normal
      in those with allergic colitis. Thus infants with proved non-infective colitis as
      a group show a high prevalence of IgA, IgG2, and IgG4 deficiency. It is likely
      that this minor deficiency of mucosa associated immunoglobulin production has a
      role in the pathogenesis of the colitic process.

PMID- 9166030
TI  - 13Carbon mixed triglyceride breath test and pancreatic enzyme supplementation in
      cystic fibrosis.
AB  - Children with cystic fibrosis have variable degrees of exocrine pancreatic
      insufficiency which, if untreated, is the main cause of fat malabsorption. The
      impact of pancreatic enzyme supplementation on fat digestion was measured in 41
      children with cystic fibrosis, 11 healthy controls, and five children with
      mucosal diseases by a non-invasive test of intraluminal lipolysis using 13carbon
      (13C) labelled mixed triglyceride (1,3-distearyl, 2[13C] octanoyl glycerol). The
      children with cystic fibrosis without pancreatic supplements had a median (range)
      13C cumulative percentage dose recovered over six hours (cPDR) of 3.1% (0-31.7),
      the controls 31.0% (21.8-41.1), and the subjects with mucosal disease 27.8% (19.7
      32.5). In 23 subjects with cystic fibrosis the usual dose of pancreatic enzyme
      supplements increased the cPDR to a median of 23.9% (0-45.6), and twice the usual
      dose of enteric coated microspheres increased the cPDR to 31.1% (11.1-47.8).
      There was no significant difference between the median cPDR of normal controls
      and children with mucosal disease, but there was a highly significant difference
      between these groups and children with untreated cystic fibrosis. Thirteen
      children with cystic fibrosis had no 13C recovery in their breath without enzymes
      and 10 showed marked increases with regular enzymes. In eight children doubling
      the dose of enzymes caused no or minimal improvement. The mixed triglyceride
      breath test offers a simple, non-invasive way of assessing the need for
      pancreatic enzyme supplementation in children with cystic fibrosis and could be
      used to optimise treatment.

PMID- 9166031
TI  - One week treatment for Helicobacter pylori infection.
AB  - Helicobacter pylori is associated with primary antral gastritis, duodenal
      ulceration, and gastric cancer. Current regimens for treating infection in
      children using bismuth and antibiotics for two to six weeks are cumbersome. The
      aim of this study was to evaluate a one week course of treatment. All children
      undergoing endoscopy were assessed for the presence of H pylori by culture,
      histology, rapid urease test, and 13C urea breath test. Infected children
      received a one week course of colloidal bismuth subcitrate 480 mg/1.73 m2/day
      (maximum 120 mg four times a day), combined with metronidazole 20 mg/kg/day
      (maximum 200 mg three times a day), and clarithromycin 15 mg/kg/day (maximum 250
      mg twice a day). To optimise compliance, drugs were dispensed in a 'Redidose' box
      containing a compartment for each day, and subcompartments marked 'breakfast',
      'lunch', 'dinner', and 'bedtime'. Compliance and side effects were assessed
      immediately after treatment. A urea breath test was performed at least one month
      after treatment. Twenty two children infected with H pylori were entered into the
      study; 20 of these took all doses; two children suffered significant side effects
      (diarrhoea and vomiting). H pylori was eradicated in 21 of the 22 children
      (95.45%; 95% confidence interval 77% to 100%). This study shows that H pylori
      infection in children can be cleared by a one week course of treatment.

PMID- 9166032
TI  - Use of sucrose as a treatment for infant colic.
AB  - AIMS: To examine if sucrose has an analgesic effect on infant colic. METHODS:
      Nineteen infants with typical infant colic were given 2 ml of 12% sucrose or
      distilled water when crying, in a double blind double crossover study. The effect
      was measured by parents' score. RESULTS: Twelve improved specifically on sucrose
      and one on placebo (p < 0.01). Five showed a non-specific improvement.
      CONCLUSIONS: Sucrose has a significant ameliorating effect on infant colic.

PMID- 9166033
TI  - Maternal comprehension of two growth monitoring charts in Sri Lanka.
AB  - OBJECTIVE: To investigate the maternal comprehension of two different growth
      charts and to identify the group of mothers with poor comprehension. DESIGN: An
      experimental prospective study. SETTING: A child welfare clinic at the De Soysa
      Hospital for Women, Colombo, Sri Lanka. SUBJECTS: 932 mothers were studied
      regarding their interpretation of the type of growth chart their infants had been
      allocated. A total of 413 mothers interpreted the 'road-to-health' chart and 519
      mothers interpreted the revised chart. A validated scoring system was used to
      assess comprehension. The two groups of mothers were comparable. RESULTS: 62.4%
      (324) mothers who interpreted the revised chart had good comprehension. Only
      20.6% (85) mothers had similar comprehension with the road-to-health chart.
      Education up to or beyond grade 8 in school significantly improved comprehension.
      CONCLUSION: The design of the growth chart has a powerful effect on maternal
      comprehension of growth patterns. Length of schooling rather than literacy alone
      is a marker of a comprehending mother. The policy implications of these findings
      are that governments and agencies may need to redesign parent held growth charts
      to achieve better comprehension by mothers.

PMID- 9166034
TI  - Basal ganglia infarction associated with HHV-6 infection.
AB  - A 6 year old boy presented with meningoencephalitis and was found to have
      serological evidence of acute human herpes virus-6 (HHV-6) infection. He did not
      develop symptomatic seizures or the rash of exanthum subitum (roseola). His
      course was marked by severe spastic quadriparesis associated with radiological
      evidence of basal ganglia infarction. HHV-6 infection should be considered in any
      child with acute meningoencephalitis.

PMID- 9166035
TI  - Profile of non-compliance in lymphoblastic leukaemia.
AB  - A nationwide study of intracellular drug metabolite concentrations in children
      prescribed 6-mercaptopurine for the treatment of lymphoblastic leukaemia was
      carried out to assess interpatient variability at a standardised dose. Nine
      children (2% of the total) had completely undetectable metabolites, indicative of
      non-compliance. Five were adolescents, but otherwise they had no obvious
      distinguishing characteristics. Not taking any 6-mercaptopurine at all is
      uncommon, but the problem cannot be predicted. The total number of children who
      do not comply cannot be determined from this study, but the nine children
      described represent only a fraction of these.

PMID- 9166036
TI  - Faulty sausage production causing methaemoglobinaemia.
AB  - A family outbreak of methaemoglobinaemia following ingestion of sausages made
      using 'saltpetre' is reported. Saltpetre is a generic term for several potassium
      and sodium based compounds. On this occasion imprecise ordering led to the use of
      sodium nitrite rather than the usual potassium nitrate, with extremely serious
      consequences.

PMID- 9166038
TI  - Surgical treatment of urinary incontinence.

PMID- 9166037
TI  - Comparing two methods of follow up in a multicentre randomised trial.
AB  - AIMS: To evaluate a parental questionnaire as a means of providing outcome
      measures for a multicentre randomised controlled trial of treatment for post
      haemorrhagic ventricular dilatation. METHODS: The parents of 88 survivors were
      sent a questionnaire before a paediatric assessment at the age of 30 months. The
      parents' responses to individual questions taken mainly from the Griffiths'
      mental development scales and their perception of the child's ability to see and
      hear were compared with the paediatric findings. A model, based on the parents'
      responses to particular questions, allowed the categorisation of the children as
      normal, impaired, moderately or severely disabled; this was compared with similar
      categorisation based on the full paediatric assessment. RESULTS: Agreement on
      items concerning gross motor function ranged between 81 and 99%, concerning
      dressing between 77 and 80%, concerning feeding between 91 and 99%, and
      concerning language between 85 and 93%. Similar proportions of children were
      identified as disabled by the parents (60%) and by the paediatrician (66%). Of 29
      children who had developmental quotients less than 70, parents identified 28 as
      disabled, 18 of them as severely disabled. They were not so good at identifying
      children with impairments without functional loss. CONCLUSIONS: Further work is
      required but there is sufficient encouragement from the results to pursue this
      methodology further for use in comparing groups in randomised trials.

PMID- 9166039
TI  - Surveillance measures of the hips of children with bilateral cerebral palsy.

PMID- 9166040
TI  - A diagnosis obscured: pyloric stenosis with situs inversus.

PMID- 9166041
TI  - Paediatric organ donors.

PMID- 9166042
TI  - Ribavirin and bronchiolitis: variation in use in the UK.

PMID- 9166043
TI  - Gene polymorphisms and the use of the bonferroni correction factor: when and when
      not to apply?

PMID- 9166044
TI  - Reproducibility of screen-film performance tests--developing standards.

PMID- 9166045
TI  - Does carotid duplex imaging render angiography redundant before carotid
      endarterectomy?
AB  - Carotid duplex imaging is now recognized as the best non-invasive screening test
      for carotid artery stenosis. The evidence for its use as the sole diagnostic
      imaging modality prior to carotid endarterectomy is examined. Providing it is
      carried out by experienced trained operators using validated duplex criteria,
      carotid duplex imaging is safe, highly sensitive and specific, and superior to
      angiography at plaque characterization and evaluation of flow disturbance.
      Cerebral CT or MRI should be performed if symptoms are atypical or if there is an
      evolved stroke. Angiography is required when duplex imaging is suboptimal or
      equivocal, in the presence of atypical symptoms or uncommon vascular
      abnormalities. In the majority of patients requiring endarterectomy for
      symptomatic high grade ICA stenosis, angiography seldom adds relevant
      information, and clinical assessment and carotid duplex imaging alone can be
      safely used in preoperative assessment.

PMID- 9166046
TI  - The ultrasound appearances of galactocoeles.
AB  - Galactocoeles are an uncommon cause of breast masses, usually occurring in
      lactating women. The purpose of this study was to review the ultrasound (US)
      features of galactocoeles presenting to the Nottingham Breast Unit. Eight women
      with galactocoeles were scanned during 1994 and 1995. All the scans were
      abnormal, 50% of lesions were cystic or multicystic, 37% mixed cystic/solid and
      13% appeared solid. A fat-fluid level was seen in only one case. Two of the
      cystic/solid lesions had ill defined solid components, raising the possibility of
      an intracystic carcinoma. All cases were confirmed by the aspiration of milk and
      clinical resolution following aspiration.

PMID- 9166047
TI  - Application of computer texture analysis to the Singh Index.
AB  - The Singh Index, which describes trabecular patterns in the proximal femur, has
      been used as a predictor for hip fractures and as an indicator of osteopenia.
      Evidence suggests that its contribution to the assessment of hip fracture risk is
      in its description of the structural properties of the femur. However,
      subjectivity in its determination may limit its practical value. In this study,
      we have used computer texture analysis to characterize the textural changes in
      trabecular bone which occur in osteoporosis. Texture analysis of the proximal
      femur was used to rank radiographs of 25 cadaver femora by Singh grading. These
      rankings were compared with those performed by two experienced radiologists. The
      computer method performed better than the least consistent individual
      radiologist, but not as well as the two radiologists in combination. The method
      required no radiologist's time after the system had been 'trained' from a set of
      example radiographs. The method has potential for use in large studies in which
      speed and consistency of measurement are important.

PMID- 9166048
TI  - Hepatic artery thrombosis and infarction: evolution of the ultrasound appearances
      in liver transplant recipients.
AB  - Hepatic infarction is a serious complication of liver transplantation, causing
      significant morbidity and mortality and often requiring retransplantation. Real
      time ultrasonography with Doppler examination is often the first imaging modality
      employed to investigate post-operative complications. We report on the
      sonographic appearances of three patients in whom hepatic infarction followed
      transplantation but who did not require retransplantation, allowing us to study
      the evolution of sonographic features. Geographic areas of decreased echogenicity
      with preservation of the portal tracts are an early sign of hepatic ischaemia and
      may either resolve completely or progress to true infarction with the development
      of transient small hyperechoic lesions. Calcification may also occur quite
      rapidly. Biliary strictures, bilomas and abscess formation are later
      complications.

PMID- 9166049
TI  - The role of metallic stents in malignant duodenal obstruction.
AB  - Malignant duodenal obstruction is a common complication of carcinoma of the head
      of the pancreas. We report successful palliative treatment of malignant duodenal
      strictures by the peroral placement of metallic endoprostheses in two patients in
      whom palliative surgery was not possible.

PMID- 9166050
TI  - An audit of knee radiographs performed for general practitioners.
AB  - The Royal College of Radiologists (RCR) has published guidelines concerning
      indications for imaging investigations. These include plain radiography of the
      knee, the indications for which are locking or signs of restricted movement. This
      audit consisted of 1153 knee radiographs in a 9 month period, results of a
      questionnaire sent to general practitioners (GPs), analysis of radiological
      reports and returned questionnaires (55% of cases), and subsequent comments from
      the GPs on receiving these results. Only 50% of cases fall within RCR guidelines,
      90% of radiographs were normal or showed degenerative change. In 42% of cases,
      knee radiographs were requested to confirm previously expected degenerative
      change, and in 30% patient pressure was a significant factor. Most knee
      radiographs (87%) result in no significant change in management apart from
      continuation of symptomatic measures. Application of current guidelines, however,
      would miss some important diagnoses manifest clinically by persistent pain or
      effusion, for example loose body or Brodie's abscess. In cases of locking, where
      a radiograph may miss significant soft tissue abnormality, there was concern that
      reassurance was often gained by a normal examination. This audit shows that many
      knee radiographs are unnecessary. The guidelines appear appropriate with the
      proviso that persistent pain and effusion should be included as indications for
      investigation. Many GPs report medico-legal considerations as important reasons
      for unnecessary referrals, although the application of guidelines should be
      protection against this. The referral rate for knee radiographs before and after
      the communication of these results has not altered.

PMID- 9166051
TI  - Optimization and deconvolution of lithium fluoride TLD-100 in diagnostic
      radiology.
AB  - Lithium fluoride (LiF) TLD-100 is one of the most commonly used thermoluminescent
      (TL) materials for the measurement of entrance surface dose (ESD) in diagnostic
      radiology. However, the minimum detectable dose (MDD) achieved, as derived from
      measurements of the random uncertainty present in the background signal, is
      usually quoted as being 50-100 microGy. A more appropriate definition of MDD for
      use in the clinical setting is the dose at which measurements exhibit a specified
      level of random uncertainty. This definition will give rise to a higher value for
      the MDD. An MDD of 50-100 microGy precludes accurate measurement of ESD in high
      tube potential (kVp) chest or neonatal radiography. Techniques described in the
      specialist literature for the reduction of the MDD of LiF were assessed both in
      the laboratory, and during a patient dose survey of high kVp chest radiography.
      Optimization of the pre-irradiation annealing and post-irradiation TL read
      heating cycles in terms of sensitivity and precision resulted in an MDD of 5/80
      microGy (derived from background signal variation and 20% random uncertainty at
      95% confidence limits, respectively). Deconvolution of the glowcurve was found to
      result in an MDD of approximately 10 microGy. Clinical measurements were
      contrasted with calculated values derived from ionization chamber measurements of
      tube output. The results support the hypothesis that glowcurve deconvolution
      permits the measurement of ESDs from low dose examinations using basic TL
      dosimetry equipment available to virtually all medical physics departments.

PMID- 9166052
TI  - Estimation of fetal and effective dose for CT examinations.
AB  - Doses from CT examinations are difficult to estimate. However, they are requested
      more frequently due to the increase in CT examinations. In particular, fetal dose
      estimations are frequently required for patients who have discovered, subsequent
      to the examination, that they were pregnant when the examination was conducted. A
      computer model has been developed to facilitate such dose calculations. This
      model combines empirical beam data with anatomical information. The model has
      been verified using thermoluminescent dosemeter (TLD) readings of internal and
      surface dose from both phantoms and patients, including intrauterine doses for
      patients undergoing afterloading gynaecological intracavitary treatment. Although
      only limited experimental data were available, the results indicate that the
      model accurately predicts uterine doses within acceptable errors. This approach
      has been validated for fetal dose estimation. The model was also used in a
      comparison with the nationally available CT dose data from the National
      Radiological Protection Board (NRPB). The two models were found to be in
      agreement for fetal dose estimations.

PMID- 9166053
TI  - A protocol for the measurement of downtime of medical equipment.
AB  - The downtime of medical equipment has become an issue of increasing concern
      within the National Health Service over recent years. No protocol exists to
      formalize measurement and recording of downtime. A survey of 129 purchasers and
      providers of radiotherapy maintenance services at 68 establishments in the UK was
      undertaken, with replies received from 66. Information was gathered on 16 factors
      affecting the measurement of downtime of radiotherapy equipment. The results of
      the survey are presented and analysed. The conclusions drawn demonstrate the
      practicality of introducing a protocol for the measurement of downtime and
      availability. A draft protocol has been developed from the results of the survey.

PMID- 9166054
TI  - In vivo measurement method of ovarian dose during barium enema examinations.
AB  - Barium enema is currently the most commonly performed fluoroscopic procedure. In
      general, it is not possible to measure directly gonadal dose in women during this
      procedure. A measurement method to allow an estimate of radiation dose to the
      ovaries is described. The method uses thermoluminescent dosimeters attached to
      the tip of the rectal tube to measure radiation dose during procedures. A series
      of measurements was made at a university hospital equipped with an image
      intensified, camera-based X-ray system and at a private clinic with a mirror
      optics X-ray system. Measurements were made on both single contrast and double
      contrast barium enema examinations. On the image-intensified, camera-based X-ray
      system, the average results of dose measurements for single and double contrast
      barium enema were 3.11 mGy and 6.50 mGy and the results for the mirror optics
      system were 1.57 mGy and 3.64 mGy, respectively.

PMID- 9166055
TI  - Radiation exposure during standard and complex interventional procedures.
AB  - Radiation doses given during standard and complex interventional procedures were
      compared. Screening times, dose-area products, and radiologists' forehead and
      finger doses were recorded during 28 standard percutaneous drainages and 10
      complex drainages (eight combined procedures and two failed procedures). The
      median screening times (8.75 min) and finger doses (84 microGy) during standard
      drainages were less than those during complex drainages (20.5 min, p = 0.0005 and
      163 microGy, p = 0.0003). Dose-area products and forehead doses were also lower,
      but not significantly. Previously published series on radiation measurements lack
      data on complex procedures. This may bias the results, since combined and failed
      interventions, which are common, are associated with higher radiation exposure
      than are standard procedures.

PMID- 9166056
TI  - A survey of current in vivo radiotherapy dosimetry practice.
AB  - A questionnaire was sent out to 57 radiotherapy physics departments in the United
      Kingdom to determine the type of dosemeters used for in vivo measurements inside
      and outside X-ray treatment fields, and whether any correction is made for energy
      dependence when the dose to critical organs outside the main beam is estimated.
      44 responses were received. 11 centres used a semi-conductor for central axis
      dosimetry compared with only two centres which used thermoluminescent dosimetry
      (TLD). 37 centres carried out dosimetry measurements outside the main beam; 25
      centres used TLD and 12 centres used a semi-conductor detector. Of the 16 centres
      measuring the dose at both sites. 11 used a semi-conductor for the central axis
      measurement, but only four of those 11 changed to TLD for critical organ
      dosimetry despite the latter's lower variation in energy response. None of the
      centres stated that they made a correction for the variation in detector energy
      response when making measurements outside the main beam, indicating a need for a
      more detailed evaluation of the energy response of these detectors and the energy
      spectra outside the main beam.

PMID- 9166057
TI  - Involvement of the inferior vena cava by adrenal phaeochromocytoma--MRI findings.
AB  - Involvement of the inferior vena cava (IVC) by adrenal phaeochromocytoma is rare.
      Only angiographic and sonographic features have been described previously. We
      present a case with magnetic resonance demonstration of the IVC invasion.

PMID- 9166058
TI  - Radiotherapy for hypoglycaemia associated with large leiomyosarcomas.
AB  - A patient with recurrent severe hypoglycaemia attacks due to a large,
      irresectable retroperitoneal leiomyosarcoma was treated with radiotherapy (60
      Gy). The blood glucose level gradually and steadily improved as the cumulative
      radiation dose was increased. Weaning of hyperalimentation was started when the
      cumulative dose reached 21.6 Gy. The patient became completely free from
      hypoglycaemic attacks despite no significant diminishment of local tumour size
      and untreated multiple lung metastases. The patient was discharged and the
      attacks did not recur until expiration as a result of tumour bleeding. This case
      report supports the clinical usefulness of radiation therapy in treating
      hypoglycaemia induced by non-islet cell tumour.

PMID- 9166059
TI  - Retained nephrostomy thread providing a nidus for atypical renal calcification.
AB  - Percutaneous nephrostomy (PCN) is a commonly performed procedure. The indications
      have expanded from merely providing emergency decompression of obstruction to
      being the initial step of many interventional procedures including percutaneous
      nephrolithotomy, ureteral stenting dilation and biopsy. Nephrostomy tube design
      has evolved from a simple trocar to the current self-retaining loop catheters.
      These catheters contain a suture which, when secured, locks the loop of the
      catheter in order to prevent accidental removal of the catheter. We present a
      case where incomplete removal of the locking suture providing the nidus for
      calcification within the renal pelvis.

PMID- 9166060
TI  - Ectopic pancreas complicated by pancreatitis and pseudocyst formation mimicking
      jejunal diverticulitis.
AB  - Clinical symptoms are rarely produced by ectopic pancreas arising in the jejunum.
      We report a case of a patient with left lower quadrant abdominal pain due to
      jejunal ectopic pancreas complicated by acute pancreatitis and pseudocyst
      formation.

PMID- 9166061
TI  - Primary multilocular cystic undifferentiated (embryonal) sarcoma of the liver in
      childhood resembling hydatid cyst of the liver.
AB  - Undifferentiated (embryonal) sarcoma (UES) is a very rare primary malignant
      tumour of the liver; typically presenting in later childhood. This tumour usually
      appears on CT and ultrasound as a predominantly solid mass with or without cystic
      areas. We report a case of primary UES which had a multilocular cystic appearance
      resembling a hydatid cyst on imaging.

PMID- 9166062
TI  - Haemoptysis: a rare cause.

PMID- 9166063
TI  - Rupture and growth of adrenal myelolipoma in two patients.

PMID- 9166064
TI  - Recommissioning of treatment planning software.

PMID- 9166065
TI  - Radiation protection in interventional radiology.

PMID- 9166066
TI  - Does magnetic resonance imaging make a difference for patients with
      musculoskeletal sarcoma?
AB  - MR imaging has had an unparalleled impact on the treatment of patients with
      musculoskeletal sarcoma. Basically, the high accuracy of local staging has made
      the introduction of reconstructive and limb salvage procedures instead of
      amputation of disarticulation available to the majority of patients with
      musculoskeletal sarcoma. Pre-operative work-up with MRI is not only more
      accurate, but also much faster and cheaper than the conventional work-up. Staging
      is the single most important reason for performing MR imaging in patients with
      musculoskeletal tumours. The impact of MR specificity is less dramatic but the
      benefit to the patient is an increased safety margin. When diagnostic errors with
      devastating consequences are made nowadays, it is usually because the proper
      protocol has not been followed. A patient with a potentially malignant, or
      equivocal, musculoskeletal mass deserves to have a combined radiographic-MRI
      examination prior to invasive procedures. MRI does not currently have a major
      impact on chemotherapy decisions and colour Doppler ultrasound has a higher
      accuracy than MRI. However, selected cases, i.e. intraosseous tumours, dynamic Gd
      enhanced MRI, can replace colour Doppler ultrasound.

PMID- 9166068
TI  - The antenatal diagnosis of fetal abnormalities: a 10 year audit of influencing
      factors.
AB  - During the 10 years 1984-1993, a total of 438 fetuses and children with a
      congenital abnormality, identified antenatally or in the first year of life, were
      registered from the North Tees Health District with the Northern Region
      Congenital Abnormality Survey (NorCAS). This represented an abnormality rate of
      2% of all births. In total, 252 structural abnormalities (57.5%) were detected by
      antenatal ultrasound examination. In spite of a targeted education programme,
      identification of cardiac lesions remained poor. The detection of structural
      abnormality by antenatal scan rose from 52% in 1984 to 85% in 1993, due mainly to
      improvements in image quality and resolution of ultrasound equipment. Also
      important was audit, based both on review of images and feedback from a
      comprehensive central register (NorCAS).

PMID- 9166067
TI  - The value of ventilation-perfusion imaging in pregnancy.
AB  - Pulmonary embolism (PE) is a major cause of maternal death during pregnancy. The
      aims of this retrospective study were to review 5 years experience of ventilation
      perfusion (V/Q) imaging in pregnancy, to evaluate the effect of the V/Q scan
      report on the referring clinician's use of anticoagulants and to monitor the
      course and outcome of pregnancy. 82 patients (aged 17-44 years, gestation 6-40
      weeks) underwent V/Q imaging for suspected PE, over a 5 year period. Modified
      PIOPED criteria were used to assess the probability of PE. 31 patients were shown
      to have normal scans (38%); 19 (23%) had low probability (LP) scans; 14 (17%) had
      intermediate probability (IP) scans and 18 (22%) had high probability (HP) scans
      for PE. Referring clinicians saw the reports and took action within 12 h.
      Anticoagulation was continued or started in 31 patients (all HP, 12 IP and 1 LP).
      Anticoagulation was considered unnecessary in 52 patients (all normal, 19 LP and
      2 IP). None of the patients with normal or LP scans had documented PE during the
      follow-up period (median 25 months, range 3-60 months). No complications of
      anticoagulation were observed and no adverse outcome of pregnancy were reported.
      V/Q imaging is a valuable technique in the management of pregnant women suspected
      of having PE.

PMID- 9166069
TI  - The natural history of the multicystic dysplastic kidney in children.
AB  - The objective of this study was to examine the natural history of the multicystic
      dysplastic kidney and the use of sonography for follow-up studies. A
      retrospective study was performed on 66 children with a radiological diagnosis of
      multicystic kidney. The change in size demonstrated on sonograms was examined.
      Adequate follow-up was available on 55 children over a period of 32 months (range
      2-69 months). 40/55 of the kidneys underwent a reduction in size, including 22
      which were no longer detectable by ultrasound. 10/55 kidneys showed an increase
      in size and 5/55 showed no change. Reduction in size occurred at a mean age of 84
      weeks (range 20-120 weeks). In conclusion, most multicystic kidneys undergo
      partial or complete involution over the first 2 years of life. The mean size of
      the multicystic kidney at diagnosis is a poor predictor of eventual outcome.

PMID- 9166070
TI  - Bolus dynamics: theoretical and experimental aspects.
AB  - This paper analyses the arterial enhancement produced by short intravenous
      boluses of iodinated contrast medium, with particular attention to the
      differences between various types of contrast media. A theoretical discussion is
      presented, followed by a small experimental study. The characteristics of the
      arterial time-attenuation curve are a function of the rate of contrast medium
      transit to the extracellular fluid (ECF), osmolality driven transit of water from
      the ECF into the plasma, direct effects on the heart and pulmonary circulation,
      the distribution of transit times in the cardiopulmonary circulation and
      recirculation. Theory predicts that while differences in peak arterial
      attenuation/peak height (PH) will be small, alterations in the areas under the
      time-attenuation curve (AUC) will reflect early-phase rate constants in the
      absence of major inotropic effects. The AUC should be higher for non-ionic than
      ionic media reflecting these lower rate constants. An experimental study on three
      healthy dogs confirmed these theoretical observations, with a slightly higher PH
      (6.5% higher) using a non-ionic medium but a substantially higher AUC (22%
      higher). (Differences significant at the 5% level, two-tailed paired t-test.) Our
      theoretical predictions and experimental findings suggest non-ionic media produce
      superior vascular enhancement, particularly shortly after injection. Possible
      clinical implications, particularly in dynamic enhanced computed tomography, are
      discussed.

PMID- 9166071
TI  - Comparing the sensitivities and specificities of two diagnostic procedures
      performed on the same group of patients.
AB  - Studies of diagnostic accuracy are the most commonly performed diagnostic tests.
      These are carried out by using Decision Matrix tables in which sensitivities,
      specificities, predictive values and other ratios are calculated and compared.
      Various recoverable pitfalls and limitations of this method have been reported.
      This study reports additional further limitations of using this method as a
      statistical analytical tool. Decision protocol and formulae are presented to show
      how the sensitivities and specificities of tests are compared in order to make a
      decision. The study also shows how special tables can be constructed for the four
      results of comparative diagnostic tests (true positive, true negative, false
      positive and false negative), and cautions against the use of some 2 x 2
      contingency tables. The procedures of how to use these special tables and
      formulae for comparing sensitivity and specificity and deriving confidence
      intervals for their difference are presented. It is also shown how it is possible
      to make a single inference from diagnostic test performance which will permit the
      determination of which test is better.

PMID- 9166073
TI  - A survey of routine head CT protocols in Australia.
AB  - The choice of scanning protocol in CT will affect the dose delivered to the
      patient. A nationwide survey of CT operators was carried out in Australia in 1994
      to determine the variation in routine head CT protocols. Only 29% of respondents
      used the supraorbitomeatal (SOM) baseline and thus avoided scanning the eyes. At
      74% of sites, the routine protocol included scans both before and after injection
      of contrast. However, the post-contrast protocol differed from that used in the
      pre-contrast series in a number of cases. Where 5 mm thick slices were used, the
      mAs was 16% higher than for 10 mm thick slices. Increased awareness of the
      influence of baseline, slice thickness/spacing and accompanying exposure factors
      on patient dose may lead to greater standardization of head CT scanning
      protocols.

PMID- 9166072
TI  - Survey of CT techniques and absorbed dose in various Dutch hospitals.
AB  - The purpose of this study was to make an inventory of the radiation dose from CT
      in the Netherlands and to relate the dose to the way the examination was
      performed. Details were obtained from approximately 3000 CT examinations carried
      out in 18 hospitals (22 CT scanners). Effective dose was calculated for each
      examination using CTDI-to-effective dose conversion factors. For most scanners,
      the conversion factors were available from the literature, for some they had to
      be derived with a computer model using a Monte Carlo algorithm. The data on
      effective dose, examination parameters and patient population are presented on a
      per hospital basis. Mean effective doses from brain CT were 0.8-5 mSv, from
      lumbar spine CT 2-12 mSv, from chest CT 6-18 mSv and from abdominal CT 6-24 mSv.
      The general indications for the various CT examinations were as follows: for the
      brain ischaemia and malignancy, for the lumbar spine disc herniation and for the
      chest and abdomen a known malignancy. This explains the relatively advanced age
      of the patients. In many hospitals intravenous contrast is used less than is
      recommended in current literature.

PMID- 9166074
TI  - Elevated trace element concentrations in malignant breast tissues.
AB  - In vitro neutron activation analysis (NAA) was performed on malignant and
      adjacent normal tissue from 46 human female breast tumours. The objective was to
      investigate the chemical environment of the tissues within which
      microcalcifications develop and to develop a method for discrimination between
      malignant and normal breast tissue. The elements Al, Br, Ca, Cl, Co, Cs, Fe, K,
      Mn, Na, Rb and Zn were significantly higher in the cancer tissues (all p < 0.001;
      except for Co, p < 0.003, Wilcoxon signed-ranks test). In addition, a significant
      correlation (0.80, Spearman rank correlation) was found for Rb and Zn in tumour
      tissues. Present results are supported by the findings of others. The relevance
      of elevated concentrations of these elements in cancer breast tissue remains a
      matter of conjecture. Evidence suggests that there is a connection both with
      increased cellular activity and blood supply and the formation of
      microcalcifications in malignant breast tissues. This study suggests an
      association between the elemental composition of breast tissues and the formation
      of breast particles. That is, elevations of elemental concentration and clustered
      calcifications in breast are possibly related.

PMID- 9166075
TI  - The use of carbon fibre material in radiographic cassettes: estimation of the
      dose and contrast advantages.
AB  - A Monte Carlo simulation has been used to estimate the dose and contrast
      advantages of replacing radiographic cassette fronts fabricated from aluminium
      with cassette fronts fabricated from low atomic number material (carbon fibre).
      The simulation used a realistic imaging geometry and calculations were made both
      with and without an anti-scatter grid. Account was taken of the scatter generated
      in the cassette front and the effect of beam hardening on primary contrast. Dose
      and contrast were evaluated for a range of cassette front thicknesses and tube
      potentials (60-150 kV) as well as for four examinations representative of
      situations with varying amounts of scatter. The results with an anti-scatter grid
      show a clear dose and contrast advantage in all cases when an aluminium cassette
      front is replaced with a low attenuation cassette front. The contrast advantage
      is dependent upon the examination and is generally greater for imaging bony
      structures than for imaging soft tissue. If a 1.74 mm aluminium cassette front is
      compared with a 1.1 mm carbon fibre cassette front, then the dose advantages are
      16%, 9%, 8% and 6% and the contrast advantages are 10%, 7%, 4% and 5% for the AP
      paediatric pelvis examination at 60 kV, the anteroposterior (AP) lumbar spine
      examination at 80 kV, the lateral lumbar spine examination at 100 kV and the
      posteroanterior (PA) chest examination at 150 kV, respectively. The results
      without an anti-scatter grid show an increased dose advantage when a low
      attenuation cassette front is used, but the contrast advantage is small and in
      some situations negative.

PMID- 9166076
TI  - Modification of the response of a quiescent cell population within a murine solid
      tumour to boron neutron capture irradiation: studies with nicotinamide and
      hyperthermia.
AB  - C3H/He mice bearing SCC VII tumours received 5-bromo-2'-deoxyuridine (BrdU)
      continuously for 5 days via implanted mini-osmotic pumps, to label all
      proliferating (P) cells. 20 min after intraperitoneal injection of sodium
      borocaptate-10B (BSH), or 3 h after oral administration of dl-p
      boronophenylalanine-10B (BPA), the tumours were irradiated with thermal neutrons.
      To modify the uptake dose of 10B, nicotinamide (NA) was intraperitoneally
      injected 60 min before the administration of 10B-compounds and/or the tumours
      were heated to 41.5 degrees C for 20 min immediately before irradiation. After
      irradiation, the tumours were excised, minced and trypsinized. The tumour cell
      suspensions were then incubated with cytochalasin-B (a cytokinesis-blocker). The
      micronucleus (MN) frequency in cells not BrdU-labelled (quiescent (Q) cells) was
      determined using immunofluorescence staining for BrdU. With or without the
      administration of 10B-compounds, the sensitivity of Q cells was lower than that
      of total (P + Q) tumour cells. With thermal neutron irradiation in the presence
      of either BPA or BSH, the MN frequency in each cell population was increased. A
      greater increase in the MN frequency of total tumour cells was observed after
      thermal neutron irradiation in the presence of BPA than in the presence of BSH.
      The distribution of 10B from BPA into tumour cells was thought to be more
      dependent on the uptake ability of the tumour cells than that from BSH.
      Sufficient quantity of 10B from these two 10B-compounds to cause a highly lethal
      event inside the cancer cell with thermal neutron irradiation could not be
      delivered to Q cells. When NA and/or heat treatment were combined with 10B
      compound administration, NA increased MN frequency in the BSH treated total
      cells, and heat treatment elevated MN frequency in Q cells. From the viewpoint of
      cell kill effect, the combined treatment with nicotinamide and heat treatment was
      more useful than treatment with either nicotinamide or heat treatment alone, not
      only in the total tumour cells but also in the Q cells.

PMID- 9166077
TI  - An audit of radiotherapy patient doses measured with in vivo semiconductor
      detectors.
AB  - Uncertainties exist both in the basic data from which a radiotherapy plan is
      produced and in the process whereby such a plan is translated into the patient
      set-up during treatment. Individual parts of the radiotherapy process are subject
      to checks, but the overall accuracy of treatment delivery is not routinely
      evaluated. In vivo dosimetry by means of a semiconductor detector system can be
      used to measure the cumulative error in the radiotherapy treatment dose
      delivered. A direct patient dosimetry system was commissioned and introduced in
      January 1993 for the routine evaluation of the doses patients receive. Since its
      introduction a total of 1000 patients have been monitored for a range of
      radiotherapy applications, comprising 300 breast treatments (6 MV X-rays), 150
      head and neck treatments (6 MV X-rays) and 550 pelvis. abdomen and thorax
      treatments (10 MV X-rays). The results of this audit show that less than 5% of
      all patients monitored gave a systematic error more than +/- 5% for a single
      field, or more than +/- 2.5% for the "estimated overall error" in the isocentre
      dose. The causes of these errors were identified and appropriate action taken
      where necessary. It is suggested that this method could be used routinely in
      radiotherapy treatment to assess the overall performance of the treatment
      process.

PMID- 9166078
TI  - Film viewing conditions in mammography.
AB  - A requirement for a minimum viewing box brightness of 3000 cd m-2 for reading
      mammograms has been widely advocated. Some recent work has challenged that
      opinion by reporting no significant variation in visibility of low contrast and
      fine detail objects over a wide range of brightness levels. This paper provides
      further experimental evidence to support the latter conclusion, at least over the
      range 1340-4190 cd m-2, and suggests that the currently recommended minimum
      viewing box brightness levels need to be revised. The importance of reducing room
      lighting levels is fully confirmed.

PMID- 9166079
TI  - Intracavitary radiotherapy boosting for nasopharynx cancer.
AB  - Intracavitary radiotherapy is conceptually an attractive method of boosting dose
      to nasopharynx cancer whilst sparing sensitive normal tissues. A high dose rate
      (HDR) microselectron can be used to deliver a brachytherapy boost conveniently,
      safely, comfortably and effectively. Following external radiotherapy a single
      outpatient treatment has been given to patients using the remote afterloading
      system of sources placed in modified paediatric endotracheal tubes. This has been
      associated with good primary control and no evidence of serious morbidity in
      eight patients. The main limitation of this method is restriction of its
      utilization to small volume primary disease.

PMID- 9166080
TI  - Imaging appearances of ileouterine fistula complicating recurrent adenocarcinoma
      of the rectum.
AB  - Enterouterine fistulae are rare and nowadays are most commonly due to pelvic
      tumours. We review the literature and present the case of a woman who presented
      with an ileouterine fistula following surgery and radiotherapy for recurrent
      rectal adenocarcinoma. The presence of tumour within the fistula track may also
      have been a significant aetiological factor. Magnetic resonance imaging (MRI) is
      an excellent method to demonstrate the site and size of the track and has not, to
      date, been used to identify such a fistula.

PMID- 9166081
TI  - Three-dimensional CT demonstration of intrahepatic portosystemic venous shunt
      draining into the inferior vena cava.
AB  - An unusual form of intrahepatic portosystemic venous shunt draining into the
      inferior vena cava was demonstrated using three-dimensional images reconstructed
      from spiral CT during arterial portography, colour Doppler ultrasonography with
      flow velocity measurement, and digital subtraction portovenography. The
      utilization of modern radiological techniques in evaluating intrahepatic
      portosystemic venous shunts is discussed.

PMID- 9166082
TI  - Diuretic renography findings in enterovesical fistula.
AB  - A 73-year-old male presented with a 2 week history of gross haematuria and faecal
      material in the urine. Bone scan for cancer work-up showed 99T(cm)-MDP
      radioactivity accumulation in the transverse and descending colon. A 99T(cm)-DTPA
      diuretic renogram was arranged to study renal function and to determine the
      location of the enterovesical fistula. Diuretic renography demonstrated
      extraurinary tract radioactivity in the sigmoid colon in the early images,
      extending to the descending and transverse colon in the subsequent dynamic
      images. A sigmoid colon adenocarcinoma with bladder wall invasion and fistula
      formation was confirmed at surgical operation. The impressive dynamic diuretic
      renography study in this patient was helpful in determining the location of the
      fistula and in planning surgical management.

PMID- 9166084
TI  - Smoke signals.

PMID- 9166083
TI  - Radiation-induced malignant mesenchymoma of the chest wall following treatment
      for breast cancer.
AB  - 21 years after radiotherapy for breast cancer, a 63-year-old woman developed a
      malignant mesenchymoma of the chest wall. The total irradiation dose was 132 Gy.
      The first clinical symptom of this second malignancy was a slight irregular
      calcification around the implanted silicon protheses observed in a conventional
      chest X-ray. Radiation-induced sarcoma is a very rare complication of
      radiotherapy. In cases of chest wall calcification after radiation therapy
      further investigation should be carried out, because some patients with radiation
      induced sarcoma could be saved, if an early diagnosis is reached.

PMID- 9166085
TI  - Miliary tuberculosis following intravesical BCG treatment.

PMID- 9166086
TI  - Skeletal haemangiomatosis presenting with spinal cord compression--postoperative
      management of progressive disease.

PMID- 9166087
TI  - Uberschwinger artefact in computed radiographs.

PMID- 9166088
TI  - A call for change in anticancer drug evaluation.
AB  - In the evaluation of anticancer agents, the present emphasis on the use of
      measurements determining the drug's capacity for cytoxicity and tumour shrinking
      prevents oncologists from defining efficacy measures which may be more relevant
      to clinical reality. In addition, oncologists are not yet making adequate or
      appropriate use of the advanced technologies available, and the use of
      standardised response criteria does not ensure that results are clinically
      meaningful. There is a strong need for flexibility in the choice of the endpoint
      to be measured according to the type of cancer. It is important that faster,
      smaller-scale trial designs must be developed so that promising, new anticancer
      agents are made available as quickly as possible.

PMID- 9166089
TI  - Anticancer drug evaluation: continuing progress from existing methodology.
AB  - Current methods of anticancer drug evaluation are responsible for past successes,
      such as the development of cisplatin and other well-established agents. Phase II
      trials based on meticulously measured response rates provide an excellent tool
      for the identification of promising compounds whose exact place in the clinic may
      be further clarified in subsequent, larger studies. On the same basis, the many
      inactive compounds may be screened out after testing them in only a handful of
      patients. After a period of lull, this established methodology is once more
      yielding important breakthroughs.

PMID- 9166090
TI  - The need for endpoints in anticancer drug trials that will simplify the clinical
      decision-making process.
AB  - The endpoints relating to antitumour effect which are commonly used are limited
      in that they give no information about the effect of the treatment on the person
      with cancer. This is particularly important in those many situations where cure
      is not a viable option. The use of quality of life as an endpoint may help to
      overcome this problem, but limitations remain. New endpoints, which simplify the
      clinical decision-making process in terms of the potential impact of treatment on
      the individual patient, are now needed. A variety of factors must be considered
      when evaluating the efficacy of an anticancer agent, including such issues as
      whether the drug is easy to use. Despite the complications this will present, in
      terms of the planning and implementing of clinical trials, the long-term benefits
      to patients and healthcare professionals would fully justify the investment of
      time and multidisciplinary expertise involved.

PMID- 9166091
TI  - A plea for improved use of the tools available for the evaluation of anticancer
      drugs.
AB  - Superb methods of anticancer drug evaluation exist, but they are still being used
      inadequately. In comparative trials, it is essential that the statistical design
      and analysis eliminate the possibility of allocation (group membership) bias,
      assessment (measurement) bias and chance before it is possible to conclude that a
      real difference exists between the two treatments under test. Oncologists should
      examine these aspects critically before accepting that a trial shows a genuine
      treatment effect.

PMID- 9166092
TI  - Non-small cell lung cancer: an overview of current management.
AB  - Non-small cell lung cancer (NSCLC) will remain a worldwide health problem for the
      foreseeable future. Unfortunately, local treatment of this disease is
      disappointing as most patients develop uncontrollable locally advanced or distant
      metastatic disease. The recent meta-analysis using updated patient data has
      suggested a potential role for adjuvant cisplatin-based chemotherapy (CT) in
      early stage disease, and has shown a significant, albeit modest, improvement in
      survival when combined with radiotherapy in locally advanced disease and as a
      single modality in metastatic disease. Although quality and cost of extra life
      with this more aggressive treatment need to be defined in prospective studies, CT
      should be considered standard treatment for patients with locally advanced and
      metastatic NSCLC able to receive cisplatin-based CT. Its role in stage I and II
      disease is under current investigation. Ongoing clinical studies with more active
      agents, novel combined modality treatment strategies and laboratory discoveries
      continue to emerge which may lead to valuable new treatment options to extend
      this survival advantage.

PMID- 9166093
TI  - Improving quality of life in patients with non-small cell lung cancer: research
      experience with gemcitabine.
AB  - Alongside objective response rate, quality of life of patients is important in
      the treatment of cancer, particularly in the palliative setting. Quality of life
      is difficult to define precisely and is correspondingly difficult to assess.
      However, a number of methods have been devised and self-report questionnaires are
      now widely used. Patients with metastatic non-small cell lung cancer (NSCLC) have
      a poor prognosis with few patients surviving longer than 8 or 9 months. Curative
      treatment is often not possible and few patients receive active treatment.
      Although some patients will accept toxic treatments in return for increased
      survival, it is generally hoped that any treatment, curative or palliative, will
      not adversely affect patients' quality of life. In three studies in which
      gemcitabine was used as a single agent in metastatic NSCLC, objective response
      rates of 20% were obtained. Gemcitabine was well tolerated. Symptoms improved in
      the studies where disease-related symptoms were assessed. The degree of
      improvement compared well with historical data on the relief offered by standard
      radiotherapy and combination chemotherapy. These findings have led to the
      initiation of a randomised trial to compare the relief offered by gemcitabine
      plus best supportive care with best supportive care, using quality of life
      assessments as a primary endpoint.

PMID- 9166094
TI  - Combination therapy with gemcitabine in non-small cell lung cancer.
AB  - The nucleoside analogue, gemcitabine, has shown activity as a single agent in the
      treatment of metastatic non-small cell lung cancer (NSCLC), producing consistent
      response rates of 20% and above. Because of its unique mechanism of action and
      its non-overlapping toxicity with other active agents, gemcitabine is an
      attractive candidate for trials in combination with other cytotoxic agents. In
      preclinical models, the cisplatin-gemcitabine combination suggested synergy
      between the two drugs. In phase I-II studies, response rates are as high as 54%
      when gemcitabine is combined with cisplatin, both in stage III and IV NSCLC. The
      combination of gemcitabine and ifosfamide is also being explored with an overall
      response rate of 32%. The gemcitabine-containing regimens showed a favourable
      safety-efficacy profile and compared well with standard regimens used in NSCLC.
      These preliminary results must be validated by large randomised trials comparing
      gemcitabine-containing regimens with NSCLC reference chemotherapy regimens.

PMID- 9166095
TI  - Assessing clinical benefit in the treatment of pancreas cancer: gemcitabine
      compared to 5-fluorouracil.
AB  - An early study with gemcitabine in pancreas cancer indicated greater relief of
      disease-related symptoms than expected from the objective tumour response rate. A
      novel design was created to assess changes in symptomatology prospectively in two
      studies. The design focuses on typical features seen in patients with advanced
      pancreas cancer (pain, impaired function, weight loss) and the endpoint is
      'clinical benefit response'. Traditional endpoints of objective tumour response
      and survival were also included. In a randomised study, the clinical benefit
      response rate for gemcitabine was 24% compared with 5% for 5-fluorouracil (5-FU)
      (P = 0.0022). The median survival was 5.65 months for gemcitabine compared with
      4.41 months for 5-FU (P = 0.0025). The corresponding objective response rates
      were 5.4% and 0%. Disease stabilised in 39% and 19% of gemcitabine and 5-FU
      patients, respectively. In a second study of 5-FU-refractory patients, 27.0% of
      patients were clinical benefit responders. The median survival in this second
      study was 3.8 months; the objective response rate was 11%, and 30% of patients
      had stable disease. These trials show that gemcitabine improves disease-related
      symptoms and survival in patients with pancreas cancer.

PMID- 9166096
TI  - Metastatic bladder cancer: advances in treatment.
AB  - At present, a combination of cisplatin, methotrexate, vinblastine and doxorubicin
      is the most widely used chemotherapy for metastatic bladder cancer. However, long
      term follow-up shows that this combination may have little effect on survival. In
      addition, this regimen is toxic. New agents are needed which combine efficacy
      with good safety profiles. Agents which have been investigated include gallium
      nitrate, interferon-alpha and paclitaxel both as single agents and in combination
      with established cytotoxic drugs. A number of studies have been conducted in
      bladder cancer with the novel nucleoside analogue, gemcitabine. Response rates of
      up to 33% have been recorded in two phase II studies. Gemcitabine was well
      tolerated in both studies with few of the side-effects normally associated with
      cytotoxic drugs. A third study is ongoing.

PMID- 9166097
TI  - Advanced breast cancer: investigational role of gemcitabine.
AB  - There have been many recent advances in the treatment of advanced breast cancer
      including the introduction of novel drugs and the development of high-dose
      chemotherapy with peripheral blood stem cell transplantation (PBSCT). These
      innovations may offer significant hope for improvement in the treatment of breast
      cancer in the near future. Gemcitabine is a nucleoside analogue with significant
      antitumour activity in many human solid tumours. Conflicting results have been
      observed from studies evaluating gemcitabine in advanced breast cancer. Efficacy
      data for single-agent gemcitabine range from 25 to 46% depending on starting dose
      and whether patients have previously received chemotherapy for metastatic disease
      (as well as adjuvant use). Gemcitabine is extremely well tolerated, even in
      heavily pre-treated patients, and is easy to administer on an outpatient basis to
      both chemo-naive and previously treated patients. The most common toxicity is
      mild myelosuppression. Gemcitabine causes minimal nausea and vomiting, and
      significant hair loss is extremely uncommon. Combination chemotherapy studies
      with anthracyclines are underway and significant activity has been observed in
      combination with both doxorubicin and epirubicin. In view of its modest toxicity
      profile, and its novel mechanism of action, gemcitabine warrants further
      evaluation in breast cancer patients, both as a single agent and in combination
      chemotherapy schedules.

PMID- 9166098
TI  - Gemcitabine in ovarian cancer: an overview of safety and efficacy.
AB  - The outlook for patients with advanced ovarian cancer is still poor. Less than
      30% survive for 5 years. The current standard chemotherapy is cisplatin-based
      combination treatment which gives response rates up to 70%. However, for patients
      who are resistant to cisplatin, new drugs are required. Response rates are
      generally low. Even with paclitaxel, remissions have been documented only in 16
      30% of patients and with considerable toxicity. A number of studies using
      gemcitabine as a single agent in cisplatin-resistant patients have been completed
      or initiated and response rates of around 20% have been recorded. As gemcitabine
      is well tolerated, studies using gemcitabine combined with paclitaxel and
      cisplatin in ovarian cancer are ongoing or planned.

PMID- 9166099
TI  - Interleukin-2 fusion protein: an investigational therapy for interleukin-2
      receptor expressing malignancies.
AB  - DAB389IL-2 is an interleukin-2 receptor (IL-2R) specific fusion protein with a
      molecular weight of 58 kD containing the enzymatic and translocation domains of
      diphtheria toxin (DT) and human IL-2. This fusion protein is able to direct the
      cytocidal action of the DT enzymatic region only to cells which bear the IL-2R.
      The human IL-2R exists in three forms: low, intermediate and high affinity. The
      high-affinity form is believed to be the biologically relevant form on mature,
      activated T-lymphocytes, B-lymphocytes and monocytes. DAB389IL-2 is able to bind
      selectively to the high-affinity IL-2R in a concentration-dependent manner, and
      once bound is internalised via receptor-mediated endocytosis. Upon acidification
      of the formed vesicle, the enzymatic portion of the fusion protein is believed to
      pass into the cytosol where it ultimately inhibits protein synthesis by
      inactivation of elongation factor-2, resulting in cell death. The constitutive
      expression of the IL-2R on certain leukaemic and lymphomatous cells of T and B
      cell origin has been reported to occur in patients with chronic lymphocytic
      leukaemia, cutaneous T cell lymphoma (CTCL), Hodgkin's disease and non-Hodgkin's
      lymphomas (NHLs). A multicentre DAB389IL-2 dose-escalation study of patients with
      IL-2R expressing lymphomas has been conducted. A 10-fold range of doses were
      evaluated on a five-daily dose schedule. Patients received up to six courses,
      with an additional two courses permitted for patients with partial responses that
      appeared to be still improving after six courses. Most adverse experiences were
      transient and mild. Preliminary assessment of response indicated five complete
      responses (CR, duration ongoing at 20, 11, 7, 5 and 4 months) and seven partial
      responses (PR, duration 3-20 months) in the 35 patients with CTCL. One CR
      (duration > 20 months) in a patient with NHL (Lennett's lymphoma) and two PR
      (duration 9 and 2 months) in 17 patients with B-cell NHL have been observed.
      Based on the mode of action of DAB389IL-2, its safety profile, and the patient
      responses associated with the phase I/II clinical trials, a phase III programme
      in CTCL patients has been initiated and plans for additional trials in NHL
      patients are targeted for 1996.

PMID- 9166101
TI  - Histopathological changes in Yucatan minipig skin following challenge with
      sulphur mustard. A sequential study of the first 24 hours following challenge.
AB  - Sulphur mustard (HD) or "mustard gas' is a potent vesicant chemical warfare agent
      whose biological effects in man have been well documented. The histopathological
      features of the developing cutaneous HD lesion in female Yucatan minipigs up to
      24 hours post exposure are reported. Following challenge with HD vapour at a
      concentration of 12.0 mumol/cm2 a sequence of ultrastructural changes to
      keratinocytes occurred which were initially seen in the stratum basale.
      Condensation of nuclear heterochromatin and loss of euchromatin was accompanied
      by cytoplasmic swelling and culminated in focal epidermal necrosis which was
      evident at 24 h after the challenge. The melanocyte appeared to be the cell type
      most sensitive to HD challenge with a loss of cytoplasmic electron density in
      areas of the cytoplasm immediately surrounding the melanosomes, chromatin
      condensation, nuclear membrane blebbing with mitochondrial and generalized
      cytoplasmic swelling. Isolated complete cell necrosis and disruption were noted
      as early as 2 h following the challenge with generalized necrosis being seen from
      12 h onwards. From 12 h onwards, areas of basement membrane degeneration were
      also observed. These appeared similar in ultrastructure to that observed in other
      animal model systems but did not progress to the large blisters so typical of the
      human lesion. Damage to the upper dermis took the form of an inflammatory
      response typified by vascular endothelial swelling and vacuolation, dermal oedema
      and inflammatory cell (mainly neutrophil) infiltration. There was some evidence
      of transitory epidermal damage outside the prescribed wound area. This finding
      may be of clinical importance when surgical treatments are being considered.

PMID- 9166100
TI  - Snake coiled fibres in rat soleus muscle in chloroquine induced myopathy share
      immunohistochemical characteristics with amyloid depositions in Alzheimer's
      disease brain tissue.
AB  - Pathological and immunopathological studies were carried out on snake coiled
      fibres (SCF) which occurred in affected soleus muscle in chloroquine treated
      rats. The SCF began to appear in denervated soleus muscle by 8 days after
      chloroquine injection. By day 14, typical SCF were observed with an unusual
      swirling pattern of the myofibrils, presenting a bizarre appearance. By day 21 or
      later, the SCF became less remarkable, and were fragmented and broken apart to
      form large vacuoles. Immunopathological studies demonstrated that the amyloid
      beta (A beta) and N and C-terminal regions of amyloid precursor protein (APP),
      and the amyloid associated proteins tested, apolipoprotein E (apoE), SP-40,40,
      alpha 1-antichymotrypsin (alpha 1-ACT), and ubiquitin, which are known to be
      components of amyloid depositions found in Alzheimer's disease (AD) affected
      brains, were present in the SCF. ApoE, SP-40,40, alpha 1-ACT, and ubiquitin are
      induced following certain cell challenges (e.g. heat shock, various drugs and
      injury). The significance of APP, A beta, and amyloid associated proteins are
      discussed in respect to snake coiled fibre formations in chloroquine rat myopathy
      and in the amyloidogenesis of AD.

PMID- 9166102
TI  - Endogenously elicited antibodies to platelet derived growth factor-BB and
      platelet cytosolic protein inhibit aortic lesion development in the cholesterol
      fed rabbit.
AB  - Several studies have indicated that growth factors, such as platelet derived
      growth factor (PDGF), may be important in atherogenesis. These factors are
      released from platelets, or expressed by cells of the arterial wall. In order to
      study their role in atherogenesis more directly, rabbits were immunized with PDGF
      BB, platelet cytosolic protein, or human serum albumin (HSA), until high titres
      of antibody were attained. Atherosclerotic lesions were subsequently induced by
      feeding the animals with a 2% cholesterol enriched diet. At the end of
      approximately 3 months, the extent of aortic lesion development was assessed by
      image analysis of en face preparations of aortae stained with Oil Red-O, and
      histological segments of aortae taken at the level of the first intercostal
      artery branch point. The endogenous antibodies were characterized with respect to
      their cross-reactivity, and ability to neutralize PDGF and platelet cytosol
      induced cell proliferation and migration in vitro. The endogenous, anti-PDGF-BB
      antibody was isoform specific, and neutralized the mitogenic and chemotactic
      properties of PDGF-BB and rabbit platelet cytosolic protein in vitro. The anti
      platelet cytosol antibody partially inhibited the chemotactic and mitogenic
      properties of rabbit platelet cytosolic protein. Compared to non-immune rabbits
      (n = 5), animals immunized with HSA (n = 4) had a significantly larger area of
      aortic lesion involvement (P < 0.01), whereas aortic lesions in rabbits immunized
      with PDGF-BB (n = 5), or platelet cytosolic protein (n = 7) were significantly
      smaller than either non-immune animals, or animals immunized with HSA (P < 0.05).
      The same pattern was observed for other measures of aortic lesion involvement
      including aortic intima:media ratio at the level of the first intercostal artery.
      These data suggest that PDGF-BB, and possibly other platelet-associated growth
      factors, are involved in cholesterol-induced atherosclerosis.

PMID- 9166103
TI  - Interleukin-10- and corticosteroid-induced reduction in type I procollagen in a
      human ex vivo scar culture.
AB  - Fibroblasts act as the effector cells of the fibrotic response via production of
      collagen. In an attempt to understand the regulation of fibroblasts from areas of
      active human tissue fibrosis, we have developed an ex vivo model in which
      biopsies of scars from patients 6 weeks post thoracotomy were cultured. This
      model has been used to investigate whether interleukin-10 (IL-10) and
      triamcinolone acetonide modulate the expression of type I procollagen mRNA and
      protein. In situ hybridization and a quantitative competitive RT-PCR were used to
      measure type I procollagen mRNA. Type I procollagen protein was evaluated by
      immunochemistry. Viability of biopsies in culture using 3H-uridine incorporation
      into RNA was observed to be > 80% for at least 96 hours. Following addition of
      either IL-10 or triamcinolone acetonide there was a modest but significant
      decrease (P < 0.05) in type I procollagen mRNA expression. Similarly, each agent
      added individually to biopsies reduced the proportion of cells staining
      positively for type I procollagen when compared to biopsies treated with medium
      alone (P < 0.05). These results extend in vitro data that IL-10 and
      corticosteroids down-regulate collagen synthesis in skin fibroblast cell lines
      and suggest that this ex vivo model may offer a closer approximation to the post
      operative scarring process when testing new therapeutic agents for reducing an
      over-exuberent fibrotic response.

PMID- 9166104
TI  - Resistance of TNF/LT alpha double deficient mice to bleomycin-induced fibrosis.
AB  - In order to evaluate the role and mode of action of TNF in bleomycin-induced lung
      fibrosis, mice deficient for TNF and LT alpha (delta TNF/LT alpha) were examined
      at 2 months of age and after 3 weekly i.v. injections of bleomycin. The body
      weight of the delta TNF/LT alpha mice was 88 +/- 11% of that of the wild type
      littermates. Lung collagen, evaluated by its hydroxyproline content, was also
      lower (81 +/- 9%) in mutant than in wild type littermates. Bleomycin induced a
      diffuse alveolitis with focal areas of alveolar remodelling in wild type but not
      in delta TNF/LT alpha, mice. Lymphoid infiltration was also prominent in wild
      type, but absent from delta TNF/LT alpha, mice. Bleomycin injections increased
      collagen deposition, as evaluated by the lung hydroxyproline content, more
      markedly in wild type, than in delta TNF/LT alpha, mice. Cell trapping in the
      alveolar capillaries was evaluated by semi-quantitative electron microscopy.
      Bleomycin markedly increased platelet trapping in the alveolar capillaries of
      wild type, but not of delta TNF/LT alpha, mice. This study indicates that the
      expression of TNF/LT alpha genes increases the deposition of collagen in both
      untreated and inflamed lung and that these genes may act, at least in part, by
      promoting platelet trapping.

PMID- 9166105
TI  - Reversal of phenobarbital-induced hyperplasia and hypertrophy in the livers of
      lpr mice.
AB  - Fas is a cell surface receptor that mediates apoptosis, and Fas mRNA has been
      demonstrated in hepatocytes. MRL/MP-lpr/lpr mice carry the mutated
      lymphoproliferation-associated gene, lpr, that codes for truncated Fas protein,
      resulting in reduced apoptotic potential in some circumstances. Phenobarbital
      treatment of experimental animals induces cytochrome P450 enzymes, and thus acts
      as a growth stimulus to the liver with both hyperplasia and hypertrophy;
      cessation results in reversion of liver to normal size with apoptosis playing a
      role. This study has determined the respective contributions of atrophy and
      apoptosis to this involution in Fas-defective and normal-FAs bearing animals.
      Between the first day and the fifth day after phenobarbital cessation, the
      weights of both Fas-defective (lpr/lpr) livers and control (lpr/+) livers
      reduced. Hepatocyte hypertrophy gradually reverted in both categories of mouse
      and this was the greater contribution to reduction in liver size. In lpr/lpr
      animals, there was a consistent level of apoptosis which remained relatively
      constant, while numbers of apoptotic cells in control livers increased over the
      period. This investigation has shown that in liver, a mechanism to execute
      apoptosis is operative even in Fas-defective mice, but it is not sensitive to
      signals activated by the removal of the growth stimulus. This is in contrast to
      mice which can mount a Fas-mediated response; thus a separate apoptotic pathway
      is indicated.

PMID- 9166106
TI  - Gonadotropin receptor mutations.

PMID- 9166107
TI  - Differential regulation of hypothalamic pituitary corticotropin releasing hormone
      receptors during development of adjuvant-induced arthritis in the rat.
AB  - The expression of corticotropin releasing hormone (CRH) in the hypothalamic
      paraventricular nucleus (PVN) and CRH receptor mRNA in the PVN and anterior
      pituitary was studied during development of adjuvant-induced arthritis in Piebald
      Viral-Glaxo rats, using in situ hybridization techniques. As previously shown
      with i.p. hypertonic saline injection, basal and immobilization stress-stimulated
      CRH mRNA levels in the PVN were significantly lower than in controls 14 days
      after adjuvant injection. However, 7 days after injection, preceding the onset of
      inflammation, the increase of CRH mRNA following immobilization was significantly
      higher than in control rats. In contrast to other chronic stress paradigms,
      inflammation stress failed to induce type-1 CRH receptor (CRH-R1) mRNA in the
      PVN, either at 7 days, or at 14 days after adjuvant injection, when inflammation
      is present. The ability of acute immobilization to induce CRH-R1 mRNA in the PVN
      was not affected 14 days after adjuvant injection but parallel to the CRH peptide
      mRNA response it was markedly potentiated at 7 days. Pro-opiomelanocorpin (POMC)
      mRNA levels in the anterior pituitary increased significantly 14 days after
      adjuvant injection, and they were unaffected by 1 h immobilization. While CRH
      binding in the pituitary decreased significantly 14 days after adjuvant
      injection, CRH-R1 mRNA was unchanged. This study shows biphasic hypothalamic
      responses to acute stress during development of adjuvant-induced arthritis, with
      enhanced CRH peptide and CRH-R1 mRNAs responses at 7 days, preceding the onset of
      inflammation, and blunted CRH mRNA responses at 14 days at the height of the
      inflammatory response. The lack of CRH receptor expression in the PVN in this
      model of chronic inflammation stress associated to low hypothalamic CRH peptide
      levels supports the view that positive feedback regulation by CRH is necessary to
      maintain enhanced CRH expression during chronic stress.

PMID- 9166108
TI  - Magnetic resonance imaging as a monitor of kidney enlargement and regression in
      experimental diabetes in rats.
AB  - The aim of the present study was to use magnetic resonance imaging as a non
      invasive measure of renal enlargement and regression in experimental diabetes in
      rats. Rats were randomized into three groups: (1) non-diabetic control animals,
      (2) diabetic animals, untreated for 30 days after streptozotocin treatment and
      (3) diabetic animals treated with insulin from day 21 to day 30 after
      streptozotocin administration. Magnetic resonance images were obtained from
      anaesthetized rats and kidney, cortex, medulla and pelvis volumes were calculated
      throughout the experiment until day 30. In untreated diabetic animals, a marked
      increase in kidney volume was seen 4 days after the induction of diabetes (P <
      0.05) and after 30 days this increase amounted to 73%, with similar increases in
      the cortex (63%) and medulla (69%). No change was seen in the pelvis volume.
      Insulin administration on day 21 to untreated diabetic rats abruptly reduced
      kidney volume by 21%, cortex volume by 27% and medulla volume by 18%, and after 4
      days all three parameters were similar to those seen in non-diabetic controls. In
      conclusion, the present study has demonstrated the applicability of magnetic
      resonance imaging as a non-invasive measure of renal enlargement and regression
      in experimental diabetes in rats. In untreated hyperglycaemic diabetic rats, with
      manifest diabetic renal enlargement, acute regression in renal volume was
      observed concomitant with insulin-induced normoglycaemia.

PMID- 9166109
TI  - Induction of 24-hydroxylase cytochrome P450 mRNA by 1,25-dihydroxyvitamin D and
      phorbol esters in normal rat kidney (NRK-52E) cells.
AB  - The biologically active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D),
      acts on intestinal, renal, and bone cells to regulate skeletal and mineral
      metabolism. 1,25(OH)2D also induces 24-hydroxylase activity in these target
      cells. The 24-hydroxylase hydroxylates 1,25(OH)2D to 1,24,25-trihydroxyvitamin D
      and 25(OH)D to 24,25-dihydroxyvitamin D. The production of 1,24,25
      trihydroxyvitamin D is thought to be the first step in the inactivation of
      1,25(OH)2D by its target tissues. Previous studies have characterized the
      induction of the 24-hydroxylase by 1,25(OH)2D in clonal cell lines from intestine
      and bone. The purpose of these studies was to characterize the induction of the
      24-hydroxylase by 1,25(OH)2D in the kidney, using the clonal rat renal cell line
      NRK-52E. 1,25(OH)2D (10(-7)M) increased the mRNA levels for the cytochrome P450
      component of the 24-hydroxylase (P450cc24) by sevenfold after 36 h in NRK-52E
      cells. 1,25(OH)2D increased P450cc24 mRNA levels in a dose-dependent manner with
      an EC50 of 10(-8) M. In parallel experiments, 1,25(OH)2D significantly increased
      24-hydroxylase enzyme activity after 48-72 h. The increase in P450cc24 mRNA
      induced by 1,25(OH)2D required ongoing transcription and translation and was
      inhibited by H-7, a protein kinase C inhibitor. Tetradecanoyl phorbol acetate
      markedly increased the magnitude of the tissue responsiveness to 1,25(OH)2D by a
      protein kinase C-dependent pathway. These studies demonstrate that 1,25(OH)2D
      increases P450cc24 mRNA levels in NRK-52E cells by a mechanism requiring new
      protein synthesis and involving protein kinase C. This is in contrast to the
      action of 1,25(OH)2D in intestinal cells, which does not require new protein
      synthesis, and in osteoblastic cells, which does not involve protein kinase C.

PMID- 9166110
TI  - Rapidly reversible binding of rabbit prolactin to the rabbit prolactin receptor
      accounts for the differences between homologous and heterologous binding.
AB  - The binding of radioiodinated rabbit (rb) prolactin (PRL) to rabbit mammary
      membranes is low and its affinity constant, 0.02 nM-1, calculated from
      heterologous inhibition assays, is about 300 times lower than that of ovine (o)
      PRL. Although the differences between homologous and heterologous binding are
      well documented in different species, the reasons for such differences are still
      unknown. Here we show that the low affinity of rbPRL for the native receptor does
      not affect its in vitro bioactivity compared with that of oPRL. We also show that
      rbPRL displays high specific binding to the baculovirus-expressed recombinant
      receptor and further establish that its lower affinity for binding to the
      homologous receptor is due to its faster and more complete dissociation compared
      with that of oPRL. Hormone binding affinity for full-length and carboxy-terminal
      truncated rbPRL receptor mutants expressed in mammalian or in baculovirus
      infected cells was not affected by partial truncation of the cytoplasmic domain
      of the receptor, whereas the affinity for oPRL increased and that for rbPRL
      decreased upon truncation of both the cytoplasmic and membrane domains. The
      affinity of rbPRL for the native receptor is two orders of magnitude lower than
      that for the recombinant receptor. Affinity cross-linking and binding experiments
      showed that this difference in affinities is not related to selective cleavage of
      the native microsomal receptor during the binding reaction; however, this
      difference may be related to cell context-dependent differences in the
      oligomerization state of the receptor. Thus, obviously, the cloned receptor is
      alone sufficient for binding to rbPRL without requiring any receptor-associated
      protein. The lower affinity for rbPRL binding to its homologous receptor in
      comparison with higher affinity binding of oPRL to the same receptor is
      attributable to differences in their dissociation kinetics and in the
      conformational requirements of the receptor-hormone interaction site for binding
      to the two hormones.

PMID- 9166111
TI  - Development, validation and application of a two-site enzyme-linked immunosorbent
      assay for activin-AB.
AB  - Monoclonal antibodies, specific for the beta A and beta B subunits of activin,
      were used to develop a new two-site ELISA for activin-AB. The assay had a
      detection limit of 0.19 ng/ml. High concentrations of activin-AB were found in
      bovine, ovine and porcine follicular fluids (FF), with less in human FF (1310,
      1730, 688 and 7 ng/ml respectively). Recovery of spiked activin-AB standard from
      human, bovine and ovine FFs and from homogenized human placental extracts
      averaged 91%, 115%, 115% and 94% respectively. Within-plate coefficients of
      variation for different concentration of activin-AB were between 1.3% and 2.67%.
      The between-plate coefficient of variation was 5.5%. Cross-reactivity experiments
      showed the high specificity of the assay for activin-AB, with inhibin-A, inhibin
      B, follistatin, activin-A and activin-B all cross-reacting < 0.2%. Incubation
      with high concentrations of follistatin (500 ng/ml) prior to assay did not affect
      the recovery of activin-AB. Samples of bovine, porcine, ovine and human FF gave
      dose responses parallel to that of the standard, as did bovine granulosa cell
      conditioned media. In human and porcine FF, levels of activin-A and activin-AB
      were similar whereas, in bovine and ovine FF, activin-A levels were approximately
      threefold higher than activin-A, nearly all of the endogenous activin-AB in
      bovine FF was detected in the eluate from gel permeation chromatography with an
      M(r) of > 700000 indicating its association with higher molecular weight binding
      protein(s). By contrast, after denaturation, immunoreactive activin-AB was
      detected with an M(r) of approximately 25000 consistent with the complete
      dissociation from binding proteins. Activin-A was detected in relatively high
      concentrations in human FF (approximately 5 ng/ml), homogenized placental
      extracts (4.35-95.5 ng/g), sera from pregnant women (> 4 ng/ml) and amniotic
      fluid (3-13 ng/ml), and in much lower concentrations in postmenopausal serum (500
      pg/ ml), normal cycle serum (100-200 pg/ml), serum from gonadotrophin-treated
      women (200 pg/ml), and normal adult male serum (225 pg/ml). Activin-A was also
      found in the culture media from explants of human amnion, chorion, maternal
      decidua and placenta. In marked contrast, activin-AB was undetectable (< 0.19
      ng/ml) in all of these samples with the exception of human FF (approximately 7
      ng/ml). In conclusion, we have developed a sensitive and specific ELISA to
      measure total (bound+free) activin-AB. Preliminary results show a more restricted
      distribution of this isoform compared with activin-A. The presence of high levels
      of both activin-A and activin-AB in FF suggests a function for both isoforms in
      the developing ovarian follicle.

PMID- 9166112
TI  - Insulin-like growth factor-I (IGF-I) production by bovine granulosa cells in
      vitro and peripheral IGF-I measurement in cattle serum: an evaluation of IGF
      binding protein extraction protocols.
AB  - Insulin-like growth factor-binding protein (IGFBP) extraction protocols were
      tested for their efficacy in removing IGFBPs from bovine plasma and bovine
      granulosa cell culture medium compared with standard acid exclusion
      chromatography. Traditional extraction methods, acidification, Sep-Pak,
      ethanol:acetone:acetic acid (EAA) and EAA-cryoprecipitation (EAA-C), failed to
      remove all the IGFBPs from both granulosa cell culture medium and plasma.
      However, EAA and EAA-C treatment of plasma samples did give values similar to
      those obtained by acid exclusion HPLC, when corrected for extraction efficiency.
      There was an inverse relationship between insulin-like growth factor-I (IGF-I)
      concentration in plasma samples, as measured using HPLC chromatography, and IGF-I
      concentration after EAA extraction. Furthermore, the interference caused by
      residual IGFBPs differed between samples taken from animals given various
      treatment that altered peripheral IGF-I concentrations. As for plasma samples,
      EAA was the most effective extraction method for culture media, but residual
      IGFBPs caused an overestimation of IGF-I concentrations. In culture media, but
      not plasma, it was possible to block the interference of IGFBPs in the IGF-I
      assay, in both extracted and non-extracted culture samples, by the addition of
      excess IGF-II. Using this assay procedure, no IGF-I production by bovine
      granulosa cells was detected. This was confirmed by HPLC acid chromatography. It
      is concluded that HPLC extraction is needed for the accurate measurement of
      peripheral IGF-I concentrations. For granulosa cell culture media it is possible
      to measure IGF-I concentration in non-extracted samples if the IGFBPs are blocked
      by adding IGF-II. Using either this assay, or after HPLC acid chromatography, no
      IGF-I was detected in culture media, suggesting that IGF-I is not produced by non
      luteinised bovine granulosa cells.

PMID- 9166113
TI  - Jurkat cell proliferative activity is increased by luteinizing hormone-releasing
      hormone.
AB  - Jurkat cells were used to study the immunomodulatory role of luteinizing hormone
      releasing hormone (LHRH) in immune cells. The Jurkat cell, a human mature
      leukemic cell line, phenotypically resembles resting human T lymphocytes and has
      been widely used to study T cell physiology. The data from this study demonstrate
      that the Jurkat cell concentration of immunoreactive LHRH was 210 +/- 36 pg/10(6)
      cells and that of proLHRH was 188 +/- 27 pg/10(6) cells (means +/- S.E.M.). The
      authenticity of this LHRH immunoreactivity is documented in two ways. First, both
      Jurkat LHRH and proLHRH immunoreactivity demonstrate dilutional parallelism with
      hypothalamic LHRH and proLHRH. Second, Jurkat lysates show LHRH bioactivity by
      releasing luteinizing hormone from rat anterior pituitary cells in culture. The
      presence of substantial amounts of LHRH in medium in which Jurkat cells were
      cultured for 72 h indicated that LHRH can be released from the cells. Using
      specific primers to exons 2 and 4 of the LHRH gene, we have found that Jurkat
      cells (like human T cells) express LHRH mRNA. The LHRH agonist, des-Gly10,D-Trp6
      LHRH ethylamide, significantly increases the proliferative activity of Jurkat
      cells, as assessed by tritiated thymidine incorporation, from 15980 +/- 1491
      c.p.m. in control to 28934 +/- 3395, 30457 +/- 3861 (P = 0.05 vs control) or
      35299 +/- 5586 c.p.m. (P < 0.01 vs control) with 10(-11), 10(-9) or 10(-7) M
      agonist respectively. LHRH antagonist, [D-pGlu1,D-Phe2,D-Trp3,6]-LHRH, at a
      concentration of 10(-8) M decreases Jurkat cell proliferative activity form 17145
      +/- 526 c.p.m. in control medium to 10653 +/- 1323 c.p.m. (P = 0.05). Co
      incubation with the LHRH antagonist completely inhibits the proliferative
      stimulation induced by the LHRH agonist. Furthermore, applying monoclonal LHRH
      antibody to Jurkat cells inhibits the cell proliferative activity assessed by
      tritiated thymidine incorporation from 19900 +/- 2675 c.p.m. in control to 15680
      +/- 2254, 15792 +/- 1854 and 9700 +/- 908 c.p.m. in media with 1:40, 1:20 and
      1:10 dilution of purified antibody respectively (P < 0.01, 1:10 dilution compared
      with control). In addition, the cAMP level in LHRH-stimulated Jurkat cells is
      decreased to 74, 27 and 57% of control levels after 15, 30 and 45 min
      respectively of exposure to 10(-7) M LHRH agonist. In summary, Jurkat cells
      produce, process and release immunoreactive and bioactive LHRH, as do normal
      human T cells. Endogenous and exogenous LHRH increase Jurkat cell proliferative
      activity, and cAMP may be involved in LHRH-induced Jurkat cell proliferation. The
      Jurkat cell may be a useful model with which to study the role of LHRH in human T
      cell function.

PMID- 9166114
TI  - Associations between insulin-like growth factor-I (IGF-I), IGF-binding protein-1,
      insulin and other metabolic measures after controlling for genetic influences:
      results from middle-aged and elderly monozygotic twins.
AB  - It has previously been shown that the serum levels of insulin-like growth factor
      I (IGF-I), IGF-binding protein-1 (IGFBP-1), and insulin are influenced by genetic
      effects to various degrees. From a clinical and preventive point of view,
      however, it is important to identify potentially modifiable non-genetic factors
      influencing the levels of these measures. Because monozygotic twin pairs share
      the same genetic background, differences in phenotypic levels within monozygotic
      twin paris are believed to be due to non-genetic influences. Accordingly, the
      associations between intrapair differences in one phenotype and intrapair
      differences in another phenotype are also due to non-genetic influences. The
      present sample of 97 pairs of monozygotic twins from the population-based Swedish
      Adoption/Twin Study of Aging (SATSA) provided the opportunity to assess non
      genetic influences on the levels of IGF-I, IGFBP-1, and insulin. Several
      metabolic measures were found to account for the variation of IGF-I, IGFBP-1, and
      insulin after controlling for the genetic influences. IGFBP-1 and glucose were
      significant predictors for the levels of IGF-I. IGFBP-1 and glucose together
      explained about one quarter of the non-genetic variation of IGF-I. However, when
      IGFBP-1 was dropped from the regression model, insulin was the only independent
      predictor of IGF-I, and explained about 19% of the non-genetic variation for IGF
      I. For IGFBP-1, insulin and IGF-I, were the significant non-genetic predictors.
      Insulin and IGF-I explained about 28 and 8% respectively of the non-genetic
      variation for IGFBP-1, while for insulin, IGF-I, triglycerides, body height,
      glucose, and body mass index (BMI) explained approximately 20, 12, 6, 5 and 5%
      respectively of the non-genetic variation.

PMID- 9166115
TI  - Possible role of corticosterone in the down-regulation of the hypothalamo
      hypophysial-thyroid axis in streptozotocin-induced diabetes mellitus in rats.
AB  - We investigated the effects of diabetes mellitus on the hypothalamo-hypophysial
      thyroid axis in male (R x U) F1 and R-Amsterdam rats, which were found to respond
      to streptozotocin (STZ)-induced diabetes mellitus with no or marked increases,
      respectively, in plasma corticosterone. Males received STZ (65 mg/kg i.v.) or
      vehicle, and were killed 1, 2 or 3 weeks later. At all times studied, STZ-induced
      diabetes mellitus resulted in reduced plasma TSH, thyroxine (T4) and 3,5,3'-tri
      iodothyronine (T3). Since the dialyzable T4 fraction increased after STZ,
      probably as a result of decreased T4-binding prealbumin, plasma free T4 was not
      altered during diabetes. In contrast, both free T3 and its dialyzable fraction
      decreased during diabetes, which was associated with an increase in T4-binding
      globulin. Hepatic activity of type I deiodinase decreased and T4 UDP
      glucuronyltransferase increased after STZ treatment. Thus, the lowered plasma T3
      during diabetes may be due to decreased hepatic T4 to T3 conversion. Median
      eminence content of TRH increased after STZ, suggesting that hypothalamic TRH
      release is reduced during diabetes and that this is not caused by impaired
      synthesis or axonal transport of TRH to the median eminence. Hypothalamic proTRH
      mRNA did not change in diabetic (R x U) F1 rats during the period of observation,
      but was lower in R-Amsterdam rats 3 weeks after STZ. Similarly, pituitary TSH and
      TSH beta mRNA had decreased in R-Amsterdam rats by 1 week after STZ treatment,
      but did not change in (R x U) F1 rats. The difference between the responses in
      diabetic R-Amsterdam and (R x U) F1 rats may be explained on the basis of plasma
      corticosterone levels which increased in R-Amsterdam rats only. Hypothalamic TRH
      content was not affected by diabetes mellitus, but the hypothalami of diabetic
      rats released less TRH in vitro than those of control rats. Moreover, insulin had
      a positive effect on TRH release in vitro. In conclusion, the reduced
      hypothalamic TRH release during diabetes is probably not caused by decreases in
      TRH synthesis or transport to the median eminence, but seems to be due to
      impaired TRH release from the median eminence which may be related to the lack of
      insulin. Inhibition of proTRH and TSH beta gene expression in diabetic R
      Amsterdam rats is not a primary event but appears to be secondary to enhanced
      adrenal activity in these animals during diabetes.

PMID- 9166116
TI  - Localization of angiotensin II receptor subtypes AT1 and AT2 in the pancreas of
      rodents.
AB  - Previous studies have demonstrated the existence of several key components of the
      renin-angiotensin system in the pancreas. In the present study, the localization
      of angiotensin II receptor subtypes, type I (AT1) and type II (AT2), in the mouse
      and the rat pancreas was studied by immunocytochemistry using specific
      antipeptide antibodies against the second extracellular loops of AT1 and AT2
      receptors in conjunction with confocal laser scanning microscopy. In the mouse,
      immunoreactivity for AT1 and AT2 was observed predominantly in the endothelia of
      the blood vessels and the epithelia of the pancreatic ductal system. Similar
      distribution of immunoreactivity for AT1 and AT2 was also observed. However, the
      intensity of immunoreactivity for AT1 and AT2 was stronger in the rat than that
      found in the mouse pancreas. Much weaker immunostaining for both AT1 and AT2, as
      compared with that found in ductal regions, was also found in the acini of the
      rodent pancreas. Together with the previous findings, the present results suggest
      that AT1 and/or AT2 receptors may play a role in regulating pancreatic functions
      in the rodent.

PMID- 9166117
TI  - Testosterone-induced susceptibility to Plasmodium chabaudi malaria: persistence
      after withdrawal of testosterone.
AB  - Testosterone induces susceptibility to Plasmodium chabaudi malaria by imposing
      restrictions on those mechanisms which mediate resistance controlled by genes of
      the H-2 complex and the non-H-2 background in mice. This study investigated
      whether these restrictions are abolished after withdrawal of testosterone. Female
      mice of the inbred strain C57BL/10 were treated with 0.9 mg testosterone twice a
      week for 3 weeks and testosterone was then withdrawn for 12 weeks. The treatment
      raised plasma testosterone levels from 0.18 ng/ml to 3.79 ng/ml. After the
      testosterone treatment, these levels progressively dropped and reached 0.21 ng/ml
      by week 12 after testosterone withdrawal. Surprisingly, however, the testosterone
      induced susceptibility still persisted. When mice were challenged on week 12
      after testosterone withdrawal, P. chabaudi infections were still fatal in
      testosterone-treated mice, in contrast to self-healing infections in resistant,
      i.e. untreated, control mice. In addition, testosterone caused a persistent
      decrease in the levels of total IgG antibodies, especially IgG1 and IgG2b
      isotypes. In contrast, testosterone-induced changes in spleen cells, such as the
      reduction in number by 50%, the relative increase in CD8+ cells and the decrease
      in Ig+ cells, as well as the acquisition of the susceptible phenotype, were
      completely reversed on week 10 after testosterone withdrawal at the latest.
      Testosterone did not affect the production of the TH1-signalling cytokine
      interferon-gamma and the TH2-signalling cytokines interleukin (IL)-4 and IL-10 in
      response to P. chabaudi malaria. Together, our data indicated that the gene
      controlled host resistance to P. chabaudi malaria is subject to superior hormonal
      imprinting: when once induced by testosterone, mechanisms which suppress
      resistance thus causing susceptibility persist independently of testosterone.

PMID- 9166118
TI  - Microinjection of rat GH but not human IGF-I into a defined area of the
      hypothalamus inhibits endogenous GH secretion in rats.
AB  - It has been surmised that GH exerts feedback action on the hypothalamus and
      thereby regulates its own secretion. Our previous studies suggested that GH acts
      on somatostatin neurons in the hypothalamic periventricular nucleus (PeV) and
      neuropeptide Y (NPY) neurons in the hypothalamic arcuate nucleus (ARC). However,
      there remains uncertainty whether GH acts directly or indirectly through the
      generation of IGFs on the hypothalamus to regulate its own secretion. To examine
      this, rat GH (rGH) or human IGF-I was injected directly into a defined area of
      the hypothalamus, and the blood GH profile was observed in conscious male rats.
      In the rats given 0.5 microgram rGH into the ARC or PeV bilaterally, GH secretion
      was inhibited, and the inhibition lasted for 12 h. During the period of
      inhibition, the duration and amplitude of GH pulses were significantly decreased
      and the episodic secretion of GH appeared irregularly compared with the vehicle
      injected control rats. In control rats given the vehicle or those given rGH into
      the lateral hypothalamus, the blood GH profile did not change and pulsatile GH
      secretion was produced every 3 h. When 0.1 microgram IGF-I was injected into the
      ARC or PeV bilaterally, the blood GH secretory pattern was not affected. Together
      with the results of our previous studies showing that c-fos gene expression was
      induced by systemic administration of GH and that GH receptor mRNA was contained
      in somatostatin neurons in the PeV and NPY neurons in the ARC, the data of the
      present study indicate that GH, but not IGF-I, acts on the cells in the ARC and
      the PeV or in their vicinity to inhibit its own secretion, presumably by
      activating the somatostatin and NPY neurons.

PMID- 9166119
TI  - Evidence for isoforms of 11 beta-hydroxysteroid dehydrogenase in the liver and
      kidney of the guinea pig.
AB  - In the human and in rodents like the rat and mouse, the liver enzyme 11 beta
      hydroxysteroid dehydrogenase type I (11 beta-HSD-I) is a functional
      oxidoreductase preferring NADP+/NADPH as cosubstrate, while the renal isoenzyme
      (11 beta-HSD-II) prefers NAD+ as cosubstrate, and seems to be a pure oxidase and
      protects the tubular, mineralocorticoid (MC) receptor from occupancy by cortisol
      and corticosterone. We studied the enzyme kinetics of 11 beta-HSDs in kidney and
      liver microsomes of the guinea pig, a species whose zoological classification is
      still a matter of debate. With a fixed concentration of 10(-6) mol/l cortisol,
      liver and kidney microsomes preferred NAD+ to NADP+ (10(-3) mol/l) for the
      conversion to cortisone. Kidney microsomes converted cortisol to cortisone with
      K(m) values of 0.64 mumol/l and 9.8 mumol/l with NAD+ and NADP+ as cosubstrates
      respectively. The reduction of cortisone to cortisol was slow with kidney
      microsomes, but could be markedly enhanced by adding an NADH/NADPH regenerating
      system: with NADPH as preferred cosubstrate, the approximate K(m) was 7.2
      mumol/l. This indicated the existence of both isoenzymes in the guinea pig
      kidney. Liver microsomes oxidized cortisol to cortisone with similar K(m) and
      Vmax values for NAD+ to NADP+ as cosubstrates (K(m) of 4.3 mumol/l and 5.0
      mumol/l respectively). The NAD+ preference for the oxidation of 10(-6) mol/l
      cortisol described above may be due to a second, NAD(+)-preferring 11 beta-HSD
      with a K(m) of 1.4 mumol/l. In contrast to the kidney, liver microsomes actively
      converted cortisone to cortisol with a preference for NADPH (K(m): 1.2 mumol/l;
      Vmax: 467 nmol/min per mg protein). Thus, the main liver enzyme is similar to the
      oxidoreductase of other species (11 beta-HSD-I) and is also present in the
      kidney, while the main kidney enzyme is clearly NAD(+)-preferring. This kidney
      enzyme (analogous to 11 beta-HSD-II of other species) seems to be suitable for
      the protection of the MC receptor from the high free plasma cortisol levels of
      the guinea pig.

PMID- 9166120
TI  - Trehalose inhibits the release of adipokinetic hormones from the corpus cardiacum
      in the African migratory locust, Locusta migratoria, at the level of the
      adipokinetic cells.
AB  - The effect of trehalose at various concentrations on the release of adipokinetic
      hormones (AKHs) from the adipokinetic cells in the glandular part of the corpus
      cardiacum of Locusta migratoria was studied in vitro. Pools of five corpora
      cardiaca or pools of five glandular parts of corpora cardiaca were incubated in a
      medium containing different concentrations of trehalose in the absence or
      presence of AKH-release-inducing agents. It was demonstrated that trehalose
      inhibits spontaneous release of AKH I in a dose-dependent manner. At a
      concentration of 80 mM, which is the concentration found in the hemolymph at
      rest, trehalose significantly decreased the release of AKH I induced by 100
      microM locustatachykinin 1, 10 microM 3-isobutyl-1-methylxanthine (IBMX) or high
      potassium concentrations. The specificity of the effect of trehalose was studied
      by incubating pools of corpora cardiaca with the non-hydrolyzable disaccharide
      sucrose or with glucose, the degradation product of trehalose, both in the
      presence and absence of 10 microM IBMX. Sucrose had no effect at all on the
      release of AKH I, whereas glucose strongly inhibited its release. The results
      point to the inhibitory effect of trehalose on the release of AKH I being
      exerted, at least partly, at the level of the adipokinetic cells, possibly after
      its conversion into glucose. The data presented in this study support the
      hypothesis that in vivo the relatively high concentration of trehalose (80 mM) at
      rest strongly inhibits the release of AKHs. At the onset of flight, the demand
      for energy substrates exceeds the amount of trehalose that can be mobilized from
      the fat body and consequently the trehalose concentration in the hemolymph
      decreases. This relieves the inhibitory effect of trehalose on the release of
      AKHs, which in turn mobilize lipids from the fat body.

PMID- 9166121
TI  - Differential effect of carbamazepine and valproate monotherapy on plasma levels
      of oestrone sulphate and dehydroepiandrosterone sulphate in male epileptic
      patients.
AB  - Steroid sulphates such as oestrone sulphate (OE1S) and dehydroepiandrosterone
      sulphate (DHEAS) have been suggested to be of biological importance in different
      disease states such as breast cancer and atherosclerosis. Previous studies have
      shown that drugs such as aminoglutethimide and rifampicin that induce P450
      dependent mixed-function oxygenases selectively suppress plasma OE1S levels. The
      aim of this study was to evaluate the influence of treatment with carbamazepine,
      an antiepileptic drug known to stimulate mixed-function oxygenases, on plasma
      levels of OE1S and DHEAS. We measured plasma OE1S and DHEAS together with other
      plasma oestrogens and androgens in male epileptic patients before and during
      carbamazepine monotherapy. Patients treated with valproate monotherapy acted as a
      control group. Treatment with carbamazepine decreased plasma OE1S levels from a
      mean value of 810.8 to 411.6 pmol/l (mean suppression to 50.7% of pretreatment
      levels, P < 0.001). Similarly, the ratio of OE1S to OE1 fell to 59.9% of
      pretreatment levels (P < 0.001)). DHEAS decreased from a mean level of 4.9
      mumol/l before treatment to 3.0 mumol/l during carbamazepine therapy (mean
      reduction to 62.7% of pretreatment levels (P < 0.001), while the ratio of DHEAS
      to DHEA fell to 63.0% of pretreatment values (P < 0.01). No significant change in
      plasma levels of the other oestrogens or androgens measured was observed.
      Treatment with valproate caused a slight decrease in FSH levels (P < 0.05), but
      no change in any of the other hormones measured was observed. Studies are
      warranted to evaluate the possible effects of long-term treatment with
      carbamazepine on the risk of developing endocrine-sensitive tumours and
      cardiovascular disease and also the possible effects of alterations in plasma
      DHEAS on epileptic activity.

PMID- 9166122
TI  - Normal pancreastatin-like and increased post-glucose insulin levels in young
      offspring of insulin-resistant non-obese essential hypertensive patients.
AB  - Pancreastatin is a regulatory peptide known to inhibit insulin secretion and
      insulin action with a glycogenolytic effect in the liver. This peptide is present
      in and secreted by many endocrine and chromaffin cells. Abnormalities of glucose,
      insulin and lipoprotein metabolism are common in patients with hypertension, as
      well as their first-degree relatives. We have recently studied a group of non
      obese hypertensive subjects in which pancreastatin-like levels were increased
      compared with controls, and correlated with norepinephrine levels. We
      hypothesized that pancreastatin alongside the sympathoadrenal system might have a
      part in the insulin resistance of these patients, and this metabolic syndrome
      could play a role in the pathogenesis and complications of hypertension. In this
      article, we studied the normotensive offspring of these nonobese hypertensive
      patients and looked for metabolic abnormalities as well as plasma pancreastatin,
      glucagon and catecholamine levels. The subjects were separated into two groups:
      (1) offspring from non-insulin-resistant patients and (2) offspring from insulin
      resistant patients. We found that after an intravenous glucose load, offspring
      from insulin-resistant patients were already hyperinsulinemic, although glucose
      clearance was normal, suggesting an early alteration in insulin sensitivity,
      whereas pancreastatin and catecholamine levels were normal compared with matched
      controls. However, offspring from non-insulin-resistant patients had no
      differences with controls. These results suggest that pancreastatin and
      catecholamines may not play an important role in triggering insulin resistance,
      although they may be important once the syndrome is established.

PMID- 9166123
TI  - Concentration of free growth hormone-binding protein in the serum of mice is not
      regulated by growth hormone.
AB  - Ames dwarf mice that do not express growth hormone (GH) or prolactin (PRL) genes
      were used to study the effects of GH deficiency on the presence and the
      characteristics of GH-binding protein (GHBP) in serum. Chromatographic techniques
      were used to allow characterization of biological rather than immunological
      activity of GHBP. Two GH-binding fractions were found in dwarf mice serum, one
      with low affinity and high capacity (GHBPI) and one with high affinity, low
      capacity and lower molecular mass (GHBPII). Serum concentration of the high
      affinity GHBP was 0.73 +/- 0.03 nM with a Kd of 6.3 +/- 1.7 nM. Since Ames dwarf
      mice have no GH in the circulation, all the GHBP is free. Interestingly, the
      concentration of GHBP in dwarf mice was similar to the levels of free GHBP
      measured in normal mice from the same line. Moreover, this value (0.7 nM) closely
      resembles the concentration of free GHBP in the serum of transgenic mice
      overexpressing GH, in which peripheral GH levels are grossly elevated. These
      observations can be interpreted as evidence that the levels of free GHBP in mouse
      serum are independent of GH concentration, and that GH influences only the levels
      of bound GHBP in peripheral circulation.

PMID- 9166124
TI  - Administration of IGF-I affects the GH axis and adolescent growth in normal
      monkeys.
AB  - The present study examined the effects of IGF-I on serum concentrations of IGF
      binding protein-3 (IGFBP-3) and GH and assessed how treatment with estradiol and
      IGF-I would stimulate adolescent growth in monkeys with normal pituitary
      function. In study I, ovariectomized, juvenile female rhesus monkeys (21 months
      of age; n = 6) received a bolus injection of IGF-I (1 mg/kg s.c.) and serum
      samples were collected periodically through 48 h. The consequential elevation in
      serum IGF-I resulted in a parallel increase in serum IGFBP-3 at 1 and 3 h after
      treatment with values returning to baseline by 7 h. In contrast, the elevation in
      serum IGF-I resulted in a significant decline in serum GH within 3 h of
      treatment. These data confirm that an elevation in IGF-I increases IGFBP-3 while
      simultaneously acting in a negative feedback capacity to inhibit GH. In study II,
      ovariectomized, juvenile female rhesus monkeys served either as controls (Con, n
      = 6) or received a constant s.c. infusion of IGF-I (300 micrograms/day; Igf, n =
      6) from 13 through 32 months of age. At approximately 26 months, females entered
      an estradiol-treatment protocol in which they received alternating blocks of 3
      weeks of estradiol followed by 3 weeks of no estradiol. As found in study I, the
      elevation in serum IGF-I resulted in a significant increase in serum IGFBP-3
      throughout the study in Igf compared with Con females. Estradiol administration
      significantly increased serum IGF-I and IGFBP-3 levels in both groups. Although
      the nano-molar ratio of IGF-I to IGFBP-3 was consistently higher in Igf females,
      the magnitude of the change in IGF-I:IGFBP-3 following estradiol treatment was
      similar between groups. Finally, the age-dependent increase in serum GH was
      dampened in Igf compared with Con females and the increase in response to
      estradiol was less in Igf females. Although total growth in crown-rump length was
      similar in both groups, Igf females grew more prior to estradiol replacement
      while Con females grew more once estradiol treatment was initiated. In addition,
      skeletal maturity was advanced more quickly in Igf females once estradiol
      treatment had been initiated. These data suggest that, in female monkeys with
      normal pituitary function, IGF-I administration inhibits endogenous GH secretion
      but is capable of stimulating crown-rump growth. Although IGF-I increased serum
      levels of IGFBP-3, the increase was not proportional to the increase in serum IGF
      I achieved by the treatment. These data would suggest that IGF-I may regulate the
      release of this binding protein but that GH may be required to maintain equi
      molar proportions of IGF-I to IGFBP-3. In addition, the observation that serum
      concentrations of IGF-I were increased further in IGF-I-treated females by the
      administration of estradiol without a change in serum GH, suggests that estradiol
      has a direct effect on IGF-I synthesis and release independent of GH.

PMID- 9166125
TI  - Occupational exposure limits for chemicals in the European Union.

PMID- 9166126
TI  - Congenital malformations and maternal occupation: a registry based case-control
      study.
AB  - OBJECTIVES: To investigate the relations between congenital malformations and
      maternal occupation during pregnancy with a registry based case-control study.
      METHODS: Analysis was performed on data derived from the Florence Eurocat
      registry surveillance programme. The study included cases with isolated
      conditions, including chromosomal anomalies (n = 1351), cases with multiple
      anomalies registered during the 1980-91 period (n = 440), and babies with no
      congenital malformations recognised at birth who were born from 1982 to 1989 and
      selected as controls (n = 3223). 11 categories were defined, 10 including cases
      with isolated malformations and one for cases with multiple congenital anomalies.
      Four categories of maternal occupation were selected for the study. Odds ratio
      (OR) values were adjusted for maternal origin, maternal and paternal education,
      number of previous live births, illness during pregnancy, and maternal age when
      the group of chromosomal anomalies was analysed. RESULTS: A notable and
      significant association between oral clefts and mothers involved in leather and
      shoe manufacturing was found (adjusted OR 3.9; 99% confidence interval (99% CI)
      1.5 to 9.8) and the risk consistently increased when considering cases with
      isolated cleft palate separately (OR 5.4; 95% CI 1.8 to 13.4). Moreover, a
      significant risk was identified for the association between multiple anomalies
      and textile dye workers (adjusted OR 1.9; 99% CI 1.0 to 3.8). CONCLUSIONS: This
      study indicates a notable, significant relation between maternal occupation as a
      pelt or leather worker and orofacial clefts in offspring. This finding is in
      agreement with the suggested inheritance models. The dilution effect due to
      studying large and heterogeneous groups of workers and occupations limits the
      value of the study; but it provides a good example of the use of a large database
      to search for teratogenic risk with the aid of malformation registries.

PMID- 9166127
TI  - Are aluminium potroom workers at increased risk of neurological disorders?
AB  - OBJECTIVE: To determine whether long term potroom workers in an aluminium smelter
      are at increased risk of neurological disorders. METHODS: Cross sectional study
      of 63 current and former aluminium potroom workers first employed before 1970 and
      with at least 10 years of service. A group of 37 cast house and carbon plant
      workers with similar durations of employment and starting dates in the same
      smelter were used as controls. The prevalence of neurological symptoms was
      ascertained by questionnaire. Objective tests of tremor in both upper and lower
      limbs, postural stability, reaction time, and vocabulary were conducted. All
      subjects were examined by a neurologist. RESULTS: No significant differences in
      age, race, or education were found between the two groups. Although the potroom
      group had higher prevalences for all but one of the neurological symptoms, only
      three odds ratios (ORs) were significantly increased; for incoordination (OR
      10.6), difficulty buttoning (OR 6.2), and depression (OR 6.2). Tests of arm or
      hand and leg tremor in both the visible and non-visible frequencies did not show
      any significant differences between the two groups. Testing of postural stability
      showed no definitive pattern of neurologically meaningful differences between the
      groups. There were no significant differences between the two groups in reaction
      time, vocabulary score, or clinical neurological assessment. CONCLUSIONS: The
      objective measures of neurological function provided little support for the
      finding of increased neurological symptom prevalences in the potroom workers,
      although increased symptoms may be an indicator of early, subtle neurological
      changes. The results provide no firm basis for concluding that neurological
      effects among long term potroom workers are related to the working environment,
      in particular aluminium exposure, in potrooms. These findings should be treated
      with caution due to the low participation of former workers and the possibility
      of information bias in the potroom group.

PMID- 9166128
TI  - Experimental exposure of male volunteers to N-methyl-2-pyrrolidone (NMP): acute
      effects and pharmacokinetics of NMP in plasma and urine.
AB  - OBJECTIVES: To study the acute effects of exposure to the increasingly used
      solvent, N-methyl-2-pyrrolidone (NMP) in male volunteers. Further, to determine
      the NMP concentration in plasma and urine during and after the exposure. METHODS:
      Six male volunteers were exposed for eight hours on four different days to 0, 10,
      25, and 50 mg/m3 NMP. Plasma was collected and urine was sampled during and after
      the exposure. Changes in nasal volume were measured by acoustic rhinometry and in
      airway resistance by spirometry. RESULTS: The eight-hour experimental exposure to
      10, 25, and 50 mg/m3 did not induce discomfort to eyes or upper airways. Acute
      changes in nasal volume were not found, and no changes in the spirometric data
      could be registered. The elimination curves suggested a non-linear pattern and at
      the end of exposure showed mean (range) half lifes of NMP in plasma of about 4.0
      (2.9-5.8) hours and in urine 4.5 (3.5-6.6) hours. The unmetabolised NMP found in
      urine samples collected during exposure and at the subsequent 44 hours
      corresponded to about 2% of the calculated absorbed dose. At the end of the
      exposure there was a close correlation between exposures and the plasma
      concentration and urinary excretion of NMP. CONCLUSIONS: NMP was absorbed through
      the respiratory tract and readily eliminated from the body, mainly by
      biotransformation to other compounds. Exposure to 10, 25, or 50 mg/m3 NMP did not
      cause nose, eye, or airway irritation. Thus, NMP is a mild irritant.

PMID- 9166130
TI  - Correlation between 99Tcm-HMPAO-SPECT brain image and a history of decompression
      illness or extent of diving experience in commercial divers.
AB  - OBJECTIVES: To explore the use of 99technetiumm-hexamethyl propylene amine oxime
      single photon computed tomography (HMPAO-SPECT) of the brain as a means of
      detecting nervous tissue damage in divers and to determine if there is any
      correlation between brain image and a diver's history of diving or decompression
      illness (DCI). METHODS: 28 commercial divers with a history of DCI, 26 divers
      with no history of DCI, and 19 non-diving controls were examined with brain HMPAO
      SPECT. Results were classified by observer assessment as normal (I) or as a
      pattern variants (II-V). The brain images of a subgroup of these divers (n = 44)
      and the controls (n = 17) were further analysed with a first order texture
      analysis technique based on a grey level histogram. RESULTS: 15 of 54 commercial
      divers (28%) were visually assessed as having HMPAO-SPECT images outside normal
      limits compared with 15.8% in appropriately identified non-diver control
      subjects. 18% of divers with a history of DCI were classified as having a pattern
      different from the normal image compared with 38% with no history of DCI. No
      association was established between the presence of a pattern variant from the
      normal image and history of DCI, diving, or other previous possible neurological
      insult. On texture analysis of the brain images, divers had a significantly lower
      mean grey level (MGL) than non-divers. Divers with a history of DCI (n = 22) had
      a significantly lower MGL when compared with divers with no history of DCI (n =
      22). Divers with > 14 years professional diving or > 100 decompression days a
      year had a significantly lower MGL value. CONCLUSIONS: Observer assessment of
      HMPAO-SPECT brain images can lead to disparity in results. Texture analysis of
      the brain images supplies both an objective and consistent method of measurement.
      A significant correlation was found between a low measure of MGL and a history of
      DCI. There was also an indication that diving itself had an effect on texture
      measurement, implying that it had caused subclinical nervous tissue damage.

PMID- 9166129
TI  - delta-Aminolevulinic acid dehydratase genotype modifies four hour urinary lead
      excretion after oral administration of dimercaptosuccinic acid.
AB  - OBJECTIVES: Previous research suggests that binding of lead by delta
      aminolevulinic acid dehydratase (ALAD) may vary by ALAD genotype. This hypothesis
      was tested by examining whether ALAD genotype modifies urinary lead excretion
      (DMSA chelatable lead) after oral administration of dimercaptosuccinic acid
      (DMSA). METHODS: 57 South Korean lead battery manufacturing workers were given 5
      mg/kg oral DMSA and urine was collected for four hours. Male workers were
      randomly selected from two ALAD genotype strata (ALAD1-1, ALAD1-2) from among all
      current workers in the two plants (n = 290). Subjects with ALAD1-1 (n = 38) were
      frequency matched with subjects with ALAD1-2 (n = 19) on duration of employment
      in the lead industry. Blood lead, zinc protoporphyrin, and plasma aminolevulinic
      acid concentrations, as well as ALAD genotype, duration of exposure, current
      tobacco use, and weight were examined as predictors or effect modifiers of levels
      of DMSA chelatable lead. RESULTS: Blood lead concentrations ranged from 11 to 53
      micrograms/dl, with a mean (SD) of 25.4 (10.2) micrograms/dl. After 5 mg/kg DMSA
      orally, the workers excreted a mean (SD) 85.4 (45.0) micrograms lead during a
      four hour urine collection (range 16.5-184.1 micrograms). After controlling for
      blood lead concentrations, duration of exposure, current tobacco use, and body
      weight, subjects with ALAD1-2 excreted, on average, 24 micrograms less lead
      during the four hour urine collection than did subjects with ALAD1-1 (P = 0.05).
      ALAD genotype seemed to modify the relation between plasma delta-aminolevulinic
      acid (ALA) and DMSA chelatable lead. Workers with ALAD1-2 excreted more lead,
      after being given DMSA, with increasing plasma ALA than did workers with ALAD1-1
      (P value for interaction = 0.01). CONCLUSIONS: DMSA chelatable lead may partly
      reflect the stores of bioavailable lead, and the current data indicate that
      subjects with ALAD1-2 have lower stores than those with ALAD1-1. These data
      provide further evidence that the ALAD genotype modifies the toxicokinetics of
      lead-for example, by differential binding of current lead stores or by
      differences in long-term retention and deposition of lead.

PMID- 9166132
TI  - Cancer mortality among magazine printing workers.
AB  - OBJECTIVE: After an inquiry from the employees of an offset printing plant, a
      historical cohort study was conducted to investigate cancer mortality among these
      workers. METHODS: The cohort comprised 262 men, who contributed 2771 person-years
      of observation. 16 deaths were identified during the follow up period (1980-91).
      Expected numbers of deaths were derived from age specific regional rates.
      Standardised mortality ratios (SMR) and 95% confidence intervals (95% CIs) were
      calculated. RESULTS: An increased cancer mortality was found after 10 years of
      employment (SMR 213, 95% CI 98 to 405, based on nine deaths), mainly due to a
      high mortality from lung cancer (SMR 381, 95% CI 104 to 975, four deaths), and
      from oesophageal cancer (SMR 1049, 95% CI 216 to 3065, three deaths). For workers
      with at least 20 years since the start of employment, the SMR was 262 (95% CI 105
      to 540) for all cancer sites, 447 (95% CI 92 to 1306) for lung cancer, and 1094
      (95% CI 132 to 3952) for oesophageal cancer. The increased cancer mortality was
      concentrated among pressmen. CONCLUSION: Although based on small numbers, the
      findings suggest an increased risk of cancer among these workers, which should be
      further investigated.

PMID- 9166131
TI  - A meta-analysis of the relation between cumulative exposure to asbestos and
      relative risk of lung cancer.
AB  - OBJECTIVES: To obtain summary measures of the relation between cumulative
      exposure to asbestos and relative risk of lung cancer from published studies of
      exposed cohorts, and to explore the sources of heterogeneity in the dose-response
      coefficient with data available in these publications. METHODS: 15 cohorts in
      which the dose-response relation between cumulative exposure to asbestos and
      relative risk of lung cancer has been reported were identified. Linear dose
      response models were applied, with intercepts either specific to the cohort or
      constrained by a random effects model; and with slopes specific to the cohort,
      constrained to be identical between cohorts (fixed effect), or constrained by a
      random effects model. Maximum likelihood techniques were used for the fitting
      procedures and to investigate sources of heterogeneity in the cohort specific
      dose-response relations. RESULTS: Estimates of the study specific dose-response
      coefficient (kappa 1.i) ranged from zero to 42 x 10(-3) ml/fibre-year (ml/f-y).
      Under the fixed effect model, a maximum likelihood estimate of the summary
      measure of the coefficient (k1) equal to 0.42 x 10(-3) (95% confidence interval
      (95% CI) 0.22 to 0.69 x 10(-3)) ml/f-y was obtained. Under the random effects
      model, implemented because there was substantial heterogeneity in the estimates
      of kappa 1.i and the zero dose intercepts (Ai), a maximum likelihood estimate of
      k1 equal to 2.6 x 10(-3) (95% CI 0.65 to 7.4 x 10(-3)) ml/f-y, and a maximum
      likelihood estimate of A equal to 1.36 (95% CI 1.05 to 1.76) were found. Industry
      category, dose measurements, tobacco habits, and standardisation procedures were
      identified as sources of heterogeneity. CONCLUSIONS: The appropriate summary
      measure of the relation between cumulative exposure to asbestos and relative risk
      of lung cancer depends on the context in which the measure will be applied and
      the prior beliefs of those applying the measure. In most situations, the summary
      measure of effect obtained under the random effects model is recommended. Under
      this model, potency, k1, is fourfold lower than that calculated by the United
      States Occupational Safety and Health Administration.

PMID- 9166133
TI  - Influence of body mass index and work activity on the prevalence of median
      mononeuropathy at the wrist.
AB  - OBJECTIVE: To determine which proposed risk factor, work activity (industrial v
      clerical), body mass index (BMI), or other demographic factors had the most
      influence on the prevalence of median mononeuropathy at the wrist, and if there
      was an interaction between the risk factors. METHODS: This was a cross sectional
      study of active workers at five different worksites; four were industrial sites
      and one was clerical. 527 workers were recruited--164 clerical and 363
      industrial. The presence of a median mononeuropathy in either hand was measured
      by electrodiagnostic techniques comparing median and ulnar sensory latencies.
      RESULTS: 30% of workers had an abnormality of the median sensory nerve at the
      wrist (34% of the industrial v 21% of the clerical workers). The adjusted risk
      for industrial workers was twice that of clerical workers. Obese workers (BMI >
      29) were four times more likely to present with a median mononeuropathy than
      workers who were normal or slender (BMI < 25). There was no significant
      interaction between BMI and worksite in relation to median mononeuropathy.
      Increasing age was also related to an increased risk of median mononeuropathy.
      CONCLUSIONS: Obesity, industrial work, and age are independent risk factors that
      influence the prevalence of median mononeuropathies among active workers.

PMID- 9166134
TI  - Physician based surveillance system for occupational respiratory diseases: the
      experience of PROPULSE, Quebec, Canada.
AB  - OBJECTIVE: To evaluate the feasibility of implementing a physician based
      surveillance system of occupational respiratory diseases (PROPULSE) in Quebec
      with regard to physician participation rate, characteristics of reported cases,
      and comparison with official statistics from the Workers' Compensation Board
      (WCB). METHODS: All chest physicians and allergists in Quebec were asked to
      report suspected new cases of occupational respiratory diseases, on a monthly
      basis, between October 1992 and September 1993. For each case, personal
      information was collected and the physician's opinion on whether the condition
      was related to work was categorised as highly likely, likely, and unlikely.
      RESULTS: Of the 161 physicians initially approached, 68% participated. Physicians
      rated 48% of suspected cases as highly likely, 29% as likely, and 20% as
      unlikely. The most often reported diagnosis was asthma (63%), followed by
      diseases related to asbestos (16%). Silicosis was less frequent (5%) but it was
      reported for six workers under 40 of whom five were involved in sandblasting
      activities. The high proportion of cases of asthma probably reflects the
      increasing importance of this disease but may also reflect the different patterns
      of reporting among physicians with different expertise. The distribution of cases
      by diagnostic category is quite different between the PROPULSE system and that of
      the WCB (annual mean number of compensated cases during a four year period).
      Asthma and allergic alveolitis are more frequent in PROPULSE, reactive airways
      dysfunction syndrome are about the same in both systems, and other diseases are
      more frequent among compensated cases. The most frequent sensitising agents
      reported for asthma were the same in both systems (isocyanates, flour, and wood
      dust). 15% of the PROPULSE cases were not covered by the WCB, and therefore would
      not be found in the board's official statistics. CONCLUSIONS: A physician based
      reporting procedure can be implemented as part of a surveillance system to
      supplement data from other sources and thus provide a better understanding of the
      occurrence of occupational respiratory diseases.

PMID- 9166135
TI  - Episode of toxic gas exposure in sewer workers.
AB  - OBJECTIVES: Sewer workers are used to unpleasant smells, but may be required to
      investigate unusual ones. Twenty six men were involved in investigation of
      episodes of such a smell after neighbourhood complaints over several weeks.
      METHODS: Workers exposed to the smell were investigated by clinical follow up,
      lung function tests, and measurement of pituitary function. RESULTS: 14 of the 26
      developed subacute symptoms including sore throat, cough, chest tightness,
      breathlessness, thirst, sweating, irritability, and loss of libido. Severity of
      symptoms seemed to be dose related. Minor symptoms resolved over several weeks
      but those more seriously affected have shown deteriorating respiratory symptoms
      and lung function and remain unable to work a year after the incident. In one,
      evidence of mild cranial diabetes insipidus was found. Analysis of gas from the
      sewer showed the presence of a mixture of thiols and sulphides, known to be
      highly odorous and not normally found in sewers. The source remains unknown.
      CONCLUSIONS: Several of these men seem to have developed delayed airways disease
      and disturbances of hypothalamic function. Such an outcome has not to our
      knowledge been described before. Despite the presence of the smell, standard
      safety gas detection equipment used to ensure the sewer was safe to enter failed
      to indicate the presence of a hazard. Protection against such incidents can only
      be provided by the use of positive pressure breathing apparatus.

PMID- 9166136
TI  - Effects of acute exposure to ultrahigh radiofrequency radiation on three antenna
      engineers.
AB  - Three men were accidentally exposed to high levels of ultrahigh frequency
      radiofrequency radiation (785 MHz mean frequency) while working on a television
      mast. They experienced an immediate sensation of intense heating of the parts of
      the body in the electromagnetic field followed by a variety of symptoms and signs
      which included pain, headache, numbness, and parasthesiae, malaise, diarrhoea,
      and skin erythema. The most notable problem was that of acute then chronic
      headache involving the part of the head which was most exposed.

PMID- 9166137
TI  - Is vinclozolin a reproductive hazard to men?

PMID- 9166138
TI  - Modifiers of non-specific symptoms in occupational and environmental syndromes.

PMID- 9166139
TI  - Physician-assisted suicide: a very personal issue.

PMID- 9166140
TI  - Induction of labor vs. antenatal monitoring in post-term pregnancy.

PMID- 9166141
TI  - Alpha blockers, diuretics and beta blockers for hypertension.

PMID- 9166142
TI  - Interferon alfa-2b therapy for chronic hepatitis.

PMID- 9166143
TI  - Euthanasia and assisted suicide: a family practice perspective.

PMID- 9166144
TI  - Microcytic anemia.
AB  - Because anemia is a condition rather than a disease, an underlying cause must be
      determined when anemia is identified. Microcytic anemia is a common category of
      anemia. Iron deficiency anemia is the most common type of microcytic anemia and
      is also the most common anemia. The clinical presentation of anemia varies
      according to its severity. Anemias resulting from chronic disease and thalassemia
      are also relatively common types of microcytic anemia and should be
      differentiated from iron deficiency to avoid repeated unnecessary trials of iron
      therapy. Low serum ferritin is the best single laboratory parameter for the
      diagnosis of iron deficiency. Serum iron, total iron binding capacity and
      hemoglobin electrophoresis, if necessary, can help differentiate the type of
      microcytic anemia in patients with normal or elevated levels of serum ferritin.
      If the evaluation identifies iron deficiency as the type of anemia, the
      underlying cause must be investigated.

PMID- 9166145
TI  - Commotio cordis: clinical implications of blunt cardiac trauma.
AB  - Blunt cardiac trauma can result not only in major structural impairments but also
      in subtle derangements without an apparent organic defect. Cardiac dysrhythmias,
      including ventricular fibrillation and sudden cardiac arrest, can occur in both
      cardiac contusion and cardiac concussion (commotio cordis) and may be fatal. The
      true incidence of these nonstructural cardiac injuries is unknown. Continuous
      electrocardiographic monitoring, assessment of cardiac troponin I and
      transesophageal echocardiograms are important aids in the evaluation of cardiac
      contusion and concussion.

PMID- 9166146
TI  - Common overuse running injuries: diagnosis and management.
AB  - Running injuries are primarily caused by overuse due to training errors (i.e.,
      running too far, too fast, too soon). A stress fracture should always be
      considered in a runner with pain, because long-term morbidity may occur if this
      injury is not recognized. The history and physical examination are usually
      sufficient to diagnose an overuse injury. Runners should be instructed to
      increase their mileage gradually in increments of 10 percent or less each week,
      to wear proper running shoes and to perform stretching and strengthening
      exercises for the lower extremities on a regular basis. In addition, they should
      not attempt to "run through pain." Treatment of overuse running injuries includes
      relative rest, nonsteroidal anti-inflammatory drugs, cross-training and
      stretching exercises, with a return to running as tolerated. Correction of
      biomechanical problems with the use of orthotics may be an adjunctive treatment
      measure.

PMID- 9166147
TI  - Adjuvant therapy for colon and rectal cancer.
AB  - Newly diagnosed colon or rectal cancer should be staged using the TNM (tumor,
      node and distant metastasis) nomenclature to determine prognostic factors. Based
      on this staging, it is possible to select patients in need of adjuvant therapy
      following surgery. In patients with stage III colon cancer, adjuvant chemotherapy
      with fluorouracil and levamisole has been shown to produce a 40 percent reduction
      in the recurrence rate at a median follow-up of 6.5 years as well as a 33 percent
      reduction in mortality. Adjuvant chemotherapy should be considered in all
      patients with stage III colon cancer and in selected patients with high-risk
      stage II colon cancer. A 34 percent improvement in disease-free interval and a 29
      percent improvement in survival have been reported for patients receiving
      fluorouracil, methyl-CCNU and radiotherapy. Adjuvant chemotherapy and
      radiotherapy are indicated in patients with stages II and III rectal cancers.

PMID- 9166148
TI  - Famciclovir: a new systemic antiviral agent for herpesvirus infections.
AB  - Acyclovir was the first antiviral drug approved for the treatment of herpes
      zoster. Several new antiviral agents have since been introduced, one of which is
      famciclovir. The pharmacokinetics of famciclovir allow a more convenient dosing
      schedule than the schedule used with acyclovir. Famciclovir is metabolized in the
      liver, but the P450 cytochrome system is not involved. Both acyclovir and
      famciclovir accelerate cutaneous healing, but studies suggest that famciclovir
      may reduce the severity of postherpetic neuralgia when compared with placebo.
      Famciclovir is currently approved only for use in immunocompetent patients, but
      clinical trials involving immunocompromised patients are in progress.

PMID- 9166149
TI  - AAP develops guidelines for hepatitis A vaccine and immune globulin in children.
      American Academy of Pediatrics.

PMID- 9166150
TI  - NCI and NIH consensus panel issue recommendations on mammography for women ages
      40 to 49.

PMID- 9166151
TI  - Intrapartum fetal asphyxia: definition, diagnosis, and classification.
AB  - Evidence of a significant metabolic acidosis, an umbilical artery base deficit >
      12 mmol/L, confirms that an asphyxial exposure has occurred. This is observed at
      delivery in approximately 2% of all pregnancies. Classification of the severity
      of the asphyxial exposure is difficult because the duration and nature of the
      exposure and the characteristics of the fetal cardiovascular response to the
      asphyxia in the affected fetus is usually not known. A classification is proposed
      in which the exposure to asphyxia is confirmed by a blood gas and acid-base
      assessment with evidence of a significant metabolic acidosis and the severity is
      defined by newborn encephalopathy and other organ system complications.
      Outstanding issues that may enhance this classification are identified.

PMID- 9166152
TI  - Obstetric determinants of neonatal survival: influence of willingness to perform
      cesarean delivery on survival of extremely low-birth-weight infants. National
      Institute of Child Health and Human Development Network of Maternal-Fetal
      Medicine Units.
AB  - OBJECTIVE: Our purpose was to evaluate the relationship between the approach to
      obstetric management and survival of extremely low-birth-weight infants. STUDY
      DESIGN: In this prospective observational study we evaluated 713 singleton births
      of infants weighing < or = 1000 gm during 1 year at the 11 tertiary perinatal
      care centers of the National Institutes of Child Health and Human Development
      network of maternal-fetal medicine units. Major anomalies, extramural delivery,
      antepartum stillbirth, induced abortion, and gestational age < 21 weeks were
      excluded. The obstetrician's opinion of viability and willingness to perform
      cesarean delivery in the event of fetal distress were ascertained from the
      medical record or interview when documentation was unclear. Grade 3 and 4
      intraventricular hemorrhage, grade 3 and 4 retinopathy of prematurity,
      necrotizing enterocolitis requiring surgery, oxygen dependence at discharge or
      120 days, and seizures were considered serious morbidity. Survival without
      serious morbidity was considered intact survival. Logistic regression was used to
      evaluate the influence of the approach to obstetric management, adjusted for
      birth weight, growth, gender, presentation, and ethnicity. RESULTS: Willingness
      to perform cesarean delivery was associated with increased likelihood of both
      survival (adjusted odds ratio 3.7, 95% confidence interval 2.3 to 6.0) and intact
      survival (adjusted odds ratio 1.8, 95% confidence interval 1.0 to 3.3).
      Willingness to intervene for fetal indications appeared to virtually eliminate
      intrapartum stillbirth and to reduce neonatal mortality. Below 800 gm or 26
      weeks, however, willingness to perform cesarean delivery was linked to an
      increased chance of survival with serious morbidity. Although obstetricians were
      willing to intervene for fetal indications in most cases by 24 weeks, willingness
      to perform cesarean delivery was associated with twice the risk for serious
      morbidity at that gestational age. CONCLUSIONS: The approach to obstetric
      management significantly influences the outcome of extremely low-birth-weight
      infants. Above 800 gm or 26 weeks the obstetrician should usually be willing to
      perform cesarean delivery for fetal indications. Between 22 and 25 weeks
      willingness to intervene results in greater likelihood of both intact survival
      and survival with serious morbidity. In these cases patients and physicians
      should be aware of the impact of the approach to obstetric management and
      consider the likelihood of serious morbidity and mortality when formulating plans
      for delivery.

PMID- 9166153
TI  - Fatal meconium aspiration in spite of appropriate perinatal airway management:
      pulmonary and placental evidence of prenatal disease.
AB  - OBJECTIVE: Our purpose was to summarize eight cases of fatal meconium aspiration
      syndrome where pathologic review showed evidence of chronic prenatal disease and
      to compare these findings with those of a group of control infants and fetuses
      who died of other causes. STUDY DESIGN: A 15-year retrospective chart review
      identified the infants who died of meconium aspiration within 48 hours of life
      and who also had autopsies performed. Neonatal pulmonary and available placental
      pathologic findings are described from these study infants and are compared with
      published norms and with autopsy results from a group of control infants and
      fetuses. RESULTS: Seven of the eight study infants underwent suctioning of the
      trachea immediately after birth. In all eight cases the neonatal lungs
      demonstrated histologic evidence of significant hypoxic changes of a chronic
      nature with onset before birth. The available placentas showed variable but
      significant abnormalities that support a case for subacute or chronic in utero
      compromise. CONCLUSIONS: As in other reports, there is evidence that meconium
      aspiration may be a prenatal rather than a postnatal disease. However, this is
      the first study that presents evidence on the basis of both pulmonary and
      placental pathologic findings and reinforces the importance of placental
      examinations in complicated pregnancies.

PMID- 9166154
TI  - First-trimester growth restriction and fetal aneuploidy: the effect of type of
      aneuploidy and gestational age.
AB  - OBJECTIVE: Our purpose was to determine the effect of type of aneuploidy and
      gestational age on first-trimester fetal growth. STUDY DESIGN: Crown-rump length
      measurement was obtained in pregnancies undergoing chorionic villus sampling in
      three large prenatal diagnosis centers. One hundred forty-four aneuploid fetuses,
      from 9 to 13 weeks' gestation, were compared with 440 matched control fetuses for
      evidence of crown-rump length shortening. Shortening was defined by the
      observed/expected crown-rump length. Expected values of crown-rump length based
      on last menstrual period were obtained from regression equations generated from a
      separate normal group. Threshold values for aneuploidy screening were determined
      on the basis of receiver-operator characteristic curves. RESULTS: There was
      significant crown-rump length shortening in trisomy 18 compared with normal
      fetuses, with observed/expected values < or = 0.80 (odds ratio 13.78, 95%
      confidence interval 5.64 to 33.88, p < 0.000001); for trisomy 13 the
      observed/expected crown-rump length was < or = 0.90 (odds ratio 3.64, 95%
      confidence interval 1.08 to 12.96, p < 0.03). There was no significant shortening
      of crown-rump length in Down syndrome, with observed/expected values < or = 0.92
      (odds ratio 0.86, 95% confidence interval 0.50 to 1.47, p = 0.6). With shortened
      crown-rump length (observed/expected value < 0.86) the risk of any aneuploidy is
      increased (odds ratio 2.52, 95% confidence interval 1.6 to 3.96, p < 0.0001).
      When the first-trimester crown-rump length was shortened by > or = 14 mm, the
      aneuploidy risk was high (odds ratio 9.04, 95% confidence interval 3.26 to 28.67,
      p < 0.00001). CONCLUSION: In the first trimester fetuses with trisomy 18 and 13
      appear to be growth restricted, in contrast to fetuses with trisomy 21. In at
      risk pregnancies crown-length that is shorter than expected significantly
      increase the odds that aneuploidy is present.

PMID- 9166155
TI  - In vitro cytokine and prostaglandin production by amnion cells in the presence of
      bacteria.
AB  - OBJECTIVE: Our goal was to evaluate the effect of group B streptococci on
      cytokine and prostaglandin production by amnion cells in vitro. STUDY DESIGN:
      Amnion cells from placentas obtained immediately after primary cesarean section
      were incubated for 48 hours with heat-inactivated group B streptococci at
      increasing concentrations. Samples for quantification of interleukin-1 beta,
      interleukin-6, interleukin-8, tumor necrosis factor-alpha, and prostaglandin E2
      were collected at 6, 12, 24, and 48 hours. RESULTS: Basal cytokine production was
      not demonstrable for any of the cytokines investigated. Incubation of amnion
      cells with bacterial antigen led to a significant increase in interleukin-6 and
      interleukin-8 production, whereas secretion of interleukin-1 beta and tumor
      necrosis factor-alpha was not enhanced. In contrast to cytokines, basal
      prostaglandin E2 production was measurable but failed to increase after addition
      of antigen. CONCLUSION: Amnion cells can be stimulated to secrete interleukin-6
      and interleukin-8 in response to streptococcal antigen. However, this rise in
      cytokines does not induce an increase in prostaglandin E2. This may be explained
      by the lack of interleukin-1 and tumor necrosis factor-alpha production, two
      cytokines that have been shown to activate prostaglandin E2 secretion by amnion
      cells.

PMID- 9166156
TI  - Superior mesenteric artery Doppler velocimetry and ultrasonographic assessment of
      fetal bowel in gastroschisis: a prospective longitudinal study.
AB  - OBJECTIVE: Our purpose was to determine whether Doppler velocimetry of the
      superior mesenteric artery and its mesenteric branches and ultrasonographic
      assessment of bowel can predict postnatal outcome in fetuses with gastroschisis.
      STUDY DESIGN: The normal reference range for the superior mesenteric artery
      pulsatility index was determined by studying 161 normal fetuses. Over a 24-month
      period superior mesenteric artery pulsatility index, superior mesenteric artery
      mesenteric branches systolic/diastolic ratio, bowel diameter, and bowel wall
      thickness were prospectively and longitudinally obtained from 17 fetuses with
      gastroschisis. Poor neonatal outcome was defined by bowel resection or staged
      repair of the defect or a hospital stay > 50 days. RESULTS: Doppler velocimetry
      of the superior mesenteric artery and its mesenteric branches proved minimally
      useful in prognosticating neonatal outcome. No difference was found in the
      superior mesenteric artery pulsatility index between the good and poor neonatal
      outcome groups (p = 0.99). Longitudinal data analysis on all fetuses with
      gastroschisis showed an increase in bowel diameter with advancing gestation (p <
      0.0001). A greater rate of increase in bowel diameter with advancing gestation
      was noted in the poor-neonatal-outcome group compared with the good-neonatal
      outcome group (p < 0.01). Mean bowel diameter obtained before delivery was
      significantly greater in the poor-neonatal-outcome group (p = 0.03). Bowel
      diameter obtained at 28 to 32 weeks was the best predictor of poor neonatal
      outcome. A cutoff value of bowel diameter > 10 mm at 28 to 32 weeks had a
      sensitivity of 83%, a specificity of 88%, a positive predictive value of 83%, and
      a negative predictive value of 88% for poor neonatal outcome. CONCLUSIONS:
      Doppler velocimetry of the superior mesenteric artery and its branches is not
      predictive of poor neonatal outcome in fetuses with gastroschisis. A bowel
      diameter > 10 mm between 28 and 32 weeks appears to be the best predictor of poor
      neonatal outcome. This newly defined variable warrants further investigation
      given its significant predictive power.

PMID- 9166157
TI  - Vaginal douching and the risk of ectopic pregnancy among black women.
AB  - OBJECTIVE: Our goal was to determine whether vaginal douching was associated with
      ectopic pregnancy among black women and whether specific douching behaviors were
      associated with differences in risk. STUDY DESIGN: We analyzed data from a case
      control study of ectopic pregnancy conducted between October 1988 and August 1990
      at a major public hospital in Atlanta, Georgia. Case subjects were 197 black
      women with surgically confirmed ectopic pregnancies; the control group included
      882 black women who were delivered of live or stillborn infants and 237 black
      women who were seeking to terminate a pregnancy. RESULTS: The adjusted odds ratio
      for ectopic pregnancy associated with ever having douched was 3.8 (95% confidence
      interval 1.6 to 8.9). The risk increased with increasing number of years of
      douching at least once per month. No douching behavior was found to be without
      risk; even women who douched for routine cleanliness were at increased risk of
      ectopic pregnancy. CONCLUSIONS: Vaginal douching is a modifiable behavior that
      may greatly increase a woman's risk of ectopic pregnancy.

PMID- 9166158
TI  - Breast health and associated premenstrual symptoms in women with severe cyclic
      mastopathy.
AB  - OBJECTIVES: A case-control study was undertaken to examine the association of
      cyclic mastopathy with premenstrual syndrome and prior breast health. STUDY
      DESIGN: A total of 34 women with severe cyclic mastopathy (cases) and 29 women
      with no significant breast symptoms (controls) prospectively recorded breast pain
      and swelling and symptoms of premenstrual syndrome during one menstrual cycle.
      They also provided information on past breast health. The two study groups were
      compared by use of standard statistical methods. RESULTS: Women with cyclic
      mastopathy reported more frequent consultations with physicians for specific
      breast lumpiness (p = 0.02) or generalized lumpiness (p = 0.004) and for all
      breast problems (p = 0.0001) and more frequent mammograms (p = 0.04), surgical
      breast biopsies (p = 0.06), and breast needle aspirations (p = 0.05).
      Premenstrual symptoms were more severe in women with cyclic mastopathy; this was
      most pronounced for physical symptoms (water retention and breast symptoms, p <
      0.001) but also present for negative affect, behavior change, and impaired
      concentration (p < 0.05). CONCLUSIONS: Women with cyclic mastopathy have a
      spectrum of breast concerns and they undergo more frequent breast investigations
      than do women without the disorder. Most symptoms of premenstrual syndrome are
      also more severe in women with cyclic mastopathy.

PMID- 9166159
TI  - Potential for an external vaginal antiitch cream containing benzocaine to cause
      methemoglobinemia in healthy women.
AB  - OBJECTIVES: Our purpose was to assess the potential for an external vaginal
      antiitch cream (20% benzocaine, 3% resorcinol) to significantly increase levels
      of methemoglobin above normal in healthy women. STUDY DESIGN: Fifty-five women
      reporting external vaginal itch were recruited for the study. Each patient was
      used as her own control with methemoglobin levels being measured before and after
      use of the cream. Women were instructed to apply a 1-inch strip of cream by
      fingertip to the external genital area three or four times a day for 7
      consecutive days. RESULTS: There were no significant differences in methemoglobin
      levels before and after use or in levels from a subgroup of women aged > 50 years
      compared with levels in a younger population. CONCLUSIONS: This preparation
      appears to be safe when used as directed; however, the results cannot be
      extrapolated to the very young. Nevertheless, lavish or frequent application over
      wide areas of excoriation might lead to toxic concentrations and
      methemoglobinemia. Therefore patients with serious vaginal disease should be
      advised against self-treatment beyond the 7-day limit imposed by the Food and
      Drug Administration for over-the-counter external analgesic medications.

PMID- 9166160
TI  - Conservative conization for microinvasive carcinoma of the cervix.
AB  - OBJECTIVE: Our purpose was to examine conservative conization as treatment for
      microinvasive carcinoma of the cervix with depth of invasion < 3 mm. STUDY
      DESIGN: Twelve patients with microinvasive carcinoma of the cervix underwent
      cervical conization under colposcopic guidance followed by careful observation.
      RESULTS: The 12 patients were alive without evidence of disease after a mean
      follow-up of 6.7 years. Four pregnancies with term deliveries were identified.
      CONCLUSION: Microinvasive carcinoma with a depth of invasion < 3 mm without
      confluent invasion or lymph vascular involvement can be treated successfully with
      conservative conization and provided a good pregnancy outcome.

PMID- 9166161
TI  - Povidone-iodine gel vaginal antisepsis for abdominal hysterectomy.
AB  - OBJECTIVE: Our goal was to assess the safety and effectiveness of vaginal
      povidone-iodine gel in reducing febrile morbidity after abdominal hysterectomy.
      STUDY DESIGN: This cohort study included 158 women treated with gel immediately
      before hysterectomy, after the usual surgical preparation, and 317 historic
      control subjects with the usual surgical preparation only, at two teaching
      hospitals. Febrile morbidity was assessed by a blinded review of temperature
      records and was analyzed by Fisher's exact test and multiple logistic regression.
      RESULTS: Febrile morbidity occurred in 17% of gel-treated patients and 26% of
      controls (adjusted odds ratio 0.52, 95% confidence interval 0.31 to 0.89). In
      patients receiving prophylactic antibiotics the adjusted odds ratio for febrile
      morbidity in gel-treated patients was 0.47 (95% confidence interval 0.27 to
      0.83). Prolonged fever occurred in 17% of controls and 10% of gel-treated
      patients (adjusted odds ratio 0.52, 95% confidence interval 0.28 to 0.97).
      CONCLUSION: Preoperative vaginal povidone-iodine gel is a safe and promising
      technique for reducing febrile morbidity after hysterectomy.

PMID- 9166162
TI  - Bone mineral changes in young women with hypothalamic amenorrhea treated with
      oral contraceptives, medroxyprogesterone, or placebo over 12 months.
AB  - OBJECTIVES: The objectives of this study were to assess (1) whether treatment
      with oral contraceptives, in comparison with medroxyprogesterone and placebo,
      improved bone mineral in women with hypothalamic amenorrhea and (2) whether
      treatment with medroxyprogesterone, in comparison with placebo, improved bone
      mineral in women with hypothalamic oligomenorrhea. STUDY DESIGN: The study was a
      randomized, controlled clinical trial. Twenty-four white women, aged 14 to 28
      years, with hypothalamic amenorrhea or oligomenorrhea were prospectively enrolled
      for a 12-month intervention period. Amenorrheic subjects were randomized to
      receive oral contraceptives, medroxyprogesterone, or placebo. Oligomenorrheic
      subjects were randomized to receive medroxyprogesterone or placebo. Bone mineral
      was measured by dual-energy x-ray absorptiometry at baseline and at 6 and 12
      months. RESULTS: In amenorrheic subjects spine and total body bone mineral
      measurements at 12 months were greater in the oral contraceptive group than in
      the medroxyprogesterone and placebo groups when baseline bone mineral
      measurements, body weight, and age were controlled for (p < or = 0.05). There
      were no differences in hip bone mineral calcium and bone mineral density
      measurements at 12 months among the three groups. In oligomenorrheic subjects
      there was no detectable improvement in bone mineral associated with
      medroxyprogesterone use. CONCLUSIONS: This study supports the hypothesis that
      oral contraceptive use in women with hypothalamic amenorrhea will improve lumbar
      spine and total body bone mineral.

PMID- 9166163
TI  - Immunohistochemistry of vascular changes in leuprolide acetate-treated
      leiomyomas.
AB  - We report two cases of leuprolide acetate-treated leiomyomas with striking
      vascular changes and histologic features of vasculitis and atherosclerosis. These
      changes may cause ischemic damage if they occur in other organs. We describe the
      histologic findings and discuss their clinical implications.

PMID- 9166164
TI  - A prospective, double-blind, randomized, controlled clinical trial of ampicillin
      sulbactam for preterm premature rupture of membranes in women receiving antenatal
      corticosteroid therapy.
AB  - OBJECTIVE: Our purpose was to test the efficacy of antibiotic prophylaxis in
      women with preterm premature rupture of the membranes who receive antenatal
      corticosteroids. STUDY DESIGN: A total of 112 women received one of three
      regimens in a double-blind randomized controlled trial: (1) ampicillin-sulbactam
      for 72 hours followed by amoxicillin-clavulanate, (2) ampicillin for 72 hours
      followed by amoxicillin, or (3) placebo. RESULTS: A total of 48.6% of neonates in
      the placebo group either died or had sepsis or respiratory distress syndrome
      versus 29.3% in the pooled antibiotic group (p < 0.05) and 26.3% in the
      ampicillin-sulbactam/amoxicillin-clavulanate subgroup (p < 0.05). All three
      neonatal deaths occurred in the placebo group (p = 0.03 versus pooled
      antibiotics). Mean birth weight was significantly greater in the pooled
      antibiotic group (1773 gm, p = 0.04) and in the ampicillin-sulbactam/amoxicillin
      clavulanate subgroup (1870 gm, p = 0.02) than in the placebo group (1543 gm).
      Antibiotic prophylaxis reduced the need for prolonged ventilation (p = 0.05).
      CONCLUSIONS: Antibiotic prophylaxis in combination with corticosteroids in
      preterm premature rupture of membranes significantly lowered the total frequency
      of neonatal mortality, sepsis, and respiratory distress syndrome and
      significantly increased birth weight compared with corticosteroids alone.

PMID- 9166165
TI  - Exposure of an infant to cervical human papillomavirus infection of the mother is
      common.
AB  - OBJECTIVE: The purpose of this study was to determine the potential of exposure
      of an infant to cervical human papillomavirus infection of the mother. STUDY
      DESIGN: Cervical scrapes of the mothers and nasopharyngeal aspirate fluids of
      their infants were analyzed at the time of delivery. The study included 106
      infants born by vaginal delivery or by cesarean section and their 105 mothers.
      Positive results were confirmed and typed by direct deoxyribonucleic acid
      sequencing or single-strand conformation polymorphism of the polymerase chain
      reaction product. RESULTS: Both the mother's and her infant's samples were
      positive for the same type of human papillomavirus in 29 mother-infant pairs.
      Interestingly, five infants born by cesarean section were found to be human
      papillomavirus deoxyribonucleic acid positive for the same human papillomavirus
      type as their mother. The overall concordance between human papillomavirus types
      in the mother and her newborn was 69% (29/42). Regardless of match in types found
      in the mother's and her infant's sample, human papillomavirus deoxyribonucleic
      acid positivity was found in 39 of all the 106 infants (37%). CONCLUSIONS: Our
      results indicate that the infant of the human papillomavirus-infected mother is
      exposed to infection even when the cervical infection of the mother is
      subclinical. The possibility of transplacental exposure has to be considered as
      well.

PMID- 9166166
TI  - Maternal serum screening for Down syndrome in the United States: a 1995 survey.
AB  - OBJECTIVE: Our goal was to determine the status of prenatal Down syndrome
      screening in the United States in 1995. STUDY DESIGN: Information was sought via
      questionnaire from laboratories participating in external proficiency testing.
      RESULTS: Services were provided to 2,498,000 women annually by 265 screening
      laboratories. All but 10 laboratories offered both open neural tube defect and
      Down syndrome screening. Twenty-one percent of Down syndrome interpretations were
      based on alpha-fetoprotein measurements alone; 79% also included other serum
      analytes. Sixty-six laboratories (26%) offered interpretations at 14 weeks'
      gestation or earlier. CONCLUSIONS: Some laboratories extend serum screening too
      early in gestation for optimal neural tube defect interpretation. When 1995 was
      compared with 1992, more women were being screened, a higher proportion were
      receiving a Down syndrome interpretation, and more interpretations were based on
      multiple analytes. Laboratories should be encouraged to use some combination of
      multiple markers when screening for Down syndrome.

PMID- 9166167
TI  - Comparison of intraocular pressure between normotensive and preeclamptic women in
      the peripartum period.
AB  - OBJECTIVE: Our purpose was to determine whether intraocular pressure differs
      between preeclamptic and normotensive women in the peripartum period. STUDY
      DESIGN: Eighteen preeclamptic (defined as blood pressure > 140/90 mm Hg and > or
      = 1+ proteinuria) and 18 normotensive women were studied. Intraocular pressure
      was determined with a handheld tonometer. Each intraocular pressure determination
      was obtained by repeatedly touching the cornea until signal averaging produced a
      single measurement with a variance < 5%. Right and left intraocular pressure,
      heart rate, and blood pressure were obtained intrapartum and 24 hours post partum
      with the patient in the seated, supine, and left lateral positions. Data are
      reported as mean +/- SD or median (range) as appropriate. Significance was set at
      p < 0.05. RESULTS: No differences existed in race, age, weight, gravidity,
      parity, cervical dilatation, and heart rate between the preeclamptic and
      normotensive groups. Gestational age was lower (39 [34 to 42] vs 41 [34 to 42]
      weeks, p = 0.003), and intrapartum mean arterial pressure (100.2 +/- 9.8 vs 81.0
      +/- 8.3 mm Hg, p < 0.001) and degree of proteinuria (3 [1 to 4] vs 0, p < 0.001)
      were higher in the preeclamptic group. There was no effect of position or
      delivery on intraocular pressure in either group. Intraocular pressure was higher
      in the preeclamptic group in the intrapartum (18.8 +/- 3.0 vs 15.3 +/- 2.7 mm Hg,
      p < 0.001) and postpartum periods (20.2 +/- 4.5 vs 15.7 +/- 3.6 mm Hg, p =
      0.002). CONCLUSION: Compared with normotensive women, preeclamptic women have
      increased intraocular pressure in the peripartum period.

PMID- 9166168
TI  - Down syndrome and neural tube defect screening: the value of using gestational
      age by ultrasonography.
AB  - OBJECTIVE: Our goal was to determine whether gestational age should be based on
      ultrasonographic evaluation or last menstrual period data in the interpretation
      of second-trimester maternal serum screening for Down syndrome and open neural
      tube defects. STUDY DESIGN: Initial and revised screen-positive rates and
      detection rates were reviewed for women undergoing triple-marker testing
      (maternal serum alpha-fetoprotein, human chorionic gonadotropin, and unconjugated
      estriol). The study population consisted of > 24,000 women at 15.0 to 21.9 weeks'
      gestation with approximately 60% of test interpretations based on
      ultrasonographic evaluation of gestational age. Gestational age and screening
      results were compared for 24 Down syndrome pregnancies in which both
      ultrasonography and last menstrual period dating were available. RESULTS: Both
      initial and revised screen-positive rates for Down syndrome were significantly
      lower when ultrasonographic data were used compared with last menstrual period
      dating. The detection rate for Down syndrome appeared to be higher with
      ultrasonographic dating (approximately 76% vs 60% for last menstrual period
      dating). Down syndrome fetuses had a significantly shorter gestational age when
      evaluated by ultrasonography (relative to last menstrual period dating), but a
      similar trend was also seen in control pregnancies. Initial and revised screen
      positive rates for open neural tube defects were higher for women who had
      received an ultrasonographic examination compared with the rates for those women
      referred with only last menstrual period data. The detection rates for open
      neural tube defects were similar for both methods of pregnancy dating.
      CONCLUSION: By use of ultrasonographic measurement of gestational age, the number
      of amniocenteses performed to detect Down syndrome can be substantially reduced
      while detection rates are maintained or improved.

PMID- 9166169
TI  - Low-molecular-weight heparin for obstetric thromboprophylaxis: experience of
      sixty-nine pregnancies in sixty-one women at high risk.
AB  - OBJECTIVE: Our purpose was to investigate the use of low-molecular-weight heparin
      (enoxaparin, Clexane) for thromboprophylaxis in pregnancy. STUDY DESIGN: A
      prospective consecutive cohort of 61 pregnant women at high risk of
      thromboembolism receiving antenatal thromboprophylaxis with enoxaparin (usually
      40 mg, subcutaneously daily) in a total of 69 pregnancies was identified from the
      obstetric medicine clinic at Queen Charlotte's Hospital. Bone density
      measurements of the hip and lumbar spine were taken in 26 women after 28
      pregnancies within 16 months post partum. Nonparametric statistics were used for
      comparisons. RESULTS: There were no episodes of antenatal thromboembolism. One
      woman (1.6%) (receiving 20 mg of enoxaparin) had a pulmonary embolus post partum.
      Heparin levels (anti-Xa assay) were greater with the 40 mg dose (median 0.09
      U/ml) than with the 20 mg dose (median 0.03 U/ml) (p = 0.0006) but were not
      affected by gestational age (r = -0.1, p = 0.14). Enoxaparin had no effect on
      platelet count or on in vitro coagulation tests. Nine (32%) women had bone
      density in the spine or hip > 1 SD below the mean for age- and sex-matched
      controls. CONCLUSION: This, the largest study to date of low-molecular-weight
      heparin use in pregnancy, confirms previous reports that it is a safe and
      effective alternative to unfractionated heparin for obstetric thromboprophylaxis
      in high-risk women. Effects on bone demineralization require further
      investigation.

PMID- 9166170
TI  - The effect of chronic nitric oxide synthesis inhibition on blood pressure and
      angiotensin II responsiveness in the pregnant rat.
AB  - OBJECTIVES: Our purpose was to determine whether blockade of inducible or
      endothelial nitric oxide synthesis prevents maternal vasodilation and blunting of
      angiotensin II responsiveness in the pregnant rat. STUDY DESIGN: Pregnant and
      nonpregnant rats were given (1) drinking water alone (untreated), (2) drinking
      water containing the inducible nitric oxide synthase inhibitor aminoguanidine
      (0.5 gm/L), or (3) drinking water containing the nonselective nitric oxide
      synthase inhibitor N omega-nitro-L-arginine methyl ester (0.5 gm/L) from
      postmating days 5 to 21. On days 7, 14, and 20, 24-hour urinary nitrate-nitrite
      excretion, urine protein concentration, hematocrit, mean arterial blood pressure,
      and pressor responses to angiotensin II (12.5 to 200 ng/kg) were measured. On day
      21 litter size, fetal weight, and fetal mortality were determined. RESULTS:
      Urinary nitrate-nitrite excretion was increased, and hematocrit and blood
      pressure were decreased by day 20 of pregnancy. Angiotensin II pressor responses
      were decreased on days 14 and 20 of pregnancy. Aminoguanidine slightly decreased
      nitrate-nitrite excretion in pregnant, but not nonpregnant rats, and abolished
      the late pregnancy increase. Aminoguanidine did not affect hematocrit, blood
      pressure, or angiotensin II responsiveness in either pregnant or nonpregnant
      rats. N omega-nitro-L-arginine methyl ester greatly reduced nitrate-nitrite
      excretion and induced hypertension in both nonpregnant and pregnant rats, but on
      day 20 blood pressure of the pregnant rats was significantly lower than that of
      the nonpregnant rats. N omega-nitro-L-arginine methyl ester increased angiotensin
      II responsiveness on days 14 and 20 only in the pregnant rats. N omega-nitro-L
      arginine methyl ester, but not aminoguanidine, increased fetal mortality and
      decreased fetal weight. CONCLUSIONS: Inducible nitric oxide synthesis accounts
      for increased nitrate-nitrite excretion during pregnancy. Endothelium-derived
      nitric oxide may attenuate angiotensin II responsiveness but does not cause
      vasodilation and the fall in blood pressure during the last week of gestation.

PMID- 9166171
TI  - Expression of beta-adrenergic receptor kinase subtypes in the pregnant rat
      myometrium.
AB  - OBJECTIVE: This study tested the hypothesis that the increase in uterine
      tachyphylaxis to beta-adrenergic stimulation during pregnancy is associated with
      increased expression of the beta-adrenergic receptor-inactivating protein
      kinases. STUDY DESIGN: Messenger ribonucleic acid was isolated from snap-frozen
      myometrium collected from nonpregnant and pregnant rats ranging from 10 to 22
      days of gestation. Autoradiographic analysis of beta-adrenergic receptor
      inactivating protein kinase messenger ribonucleic acid expression was performed
      after hybridization with specific complementary deoxyribonucleic acid probes for
      types 1 and 2 beta-adrenergic receptor-inactivating protein kinases. Probe
      specific hybridization was normalized for ribosomal ribonucleic acid detected
      with methylene blue. Protein expression was detected by Western analysis with use
      of specific polyclonal antibodies. RESULTS: Myometrial beta-adrenergic receptor
      inactivating protein kinase type 2 messenger ribonucleic acid and protein levels
      increased during the course of pregnancy and in postpartum day 1. In contrast,
      type 1 levels remained unchanged during the same period. Estrogen treatment
      resulted in a modest 20% decrease in messenger ribonucleic acid levels of both
      subtypes. This effect was reversed with progesterone treatment. CONCLUSION: These
      results suggest that the myometrium undergoes a functional remodeling late in
      pregnancy to a state promoting myometrial contractions. The increased myometrial
      expression of type 2 beta-adrenergic receptor-inactivating kinase may explain the
      decreased effectiveness of beta 2-adrenergic receptor-mediated contraction
      inhibition at the end of pregnancy and labor.

PMID- 9166172
TI  - Prenatal analysis of rhesus CcDEe blood groups by heteroduplex generator.
AB  - OBJECTIVE: Our purpose was to determine the efficacy of the heteroduplex
      generator in the prenatal analysis of rhesus CcDEe blood groups. STUDY DESIGN: A
      cross-sectional study was performed evaluating fetal samples from 85 women
      undergoing prenatal diagnosis and comparing the results with standard immunologic
      serotyping on cord blood delivery. RESULTS: Of the 85 samples, 64 were tested,
      for all CcDEe alleles: one case was discrepant. Twenty-one cases were tested
      solely for the D antigen. Two novel genotypes were detected in the population by
      heteroduplex generator and confirmed by deoxyribonucleic acid sequencing. Five
      cases were indeterminate because of an indistinct banding pattern. CONCLUSIONS:
      Heteroduplex analysis can identify rhesus blood group alleles and is inexpensive,
      rapid, and does not use radioactive isotopes.

PMID- 9166173
TI  - Transdermal nicotine replacement in pregnancy: maternal pharmacokinetics and
      fetal effects.
AB  - OBJECTIVE: Our purpose was to measure any short-term effects that the transdermal
      nicotine replacement system may have in pregnancy and to verify salivary nicotine
      and cotinine levels during patch placement. STUDY DESIGN: After customary smoking
      cessation efforts had failed, six prenatal patients between 28 and 37 weeks'
      gestation who smoked between one and two packs per day were enrolled in this
      prospective study. The patients were admitted to the General Clinical Research
      Center for a period of 21 hours. During hospitalization we performed maternal and
      fetal assessments including vital signs, biophysical profile and electronic fetal
      monitoring, amniotic fluid index, and umbilical artery Doppler examinations.
      Salivary samples for cotinine and nicotine levels were collected at standard
      intervals. RESULTS: There were no measurable differences in fetal or maternal
      well-being. During patch use salivary nicotine levels increased as expected, to a
      mean value of 19.0 +/- 13.5 micrograms/L at 480 minutes. Salivary cotinine
      concentrations remained low (approximately 50 micrograms/L) and varied little
      during the 480-minute period that the patch was worn. Overall, patients were
      satisfied with the transdermal patches. CONCLUSION: There were no adverse
      maternal or fetal effects from the transdermal nicotine replacement system over
      the 6-hour period. Salivary nicotine concentrations were consistent with those
      seen in nonpregnant adults. Surprisingly, salivary cotinine concentrations were
      much lower than those seen in smoking nonpregnant adults.

PMID- 9166174
TI  - Effect of zidovudine on blood composition of the pregnant and fetal baboon.
AB  - OBJECTIVE: Our purpose was to assess the effect of intravenous zidovudine on
      placental function and fetal well-being. STUDY DESIGN: Eighteen chronically
      instrumented third-trimester pregnant baboons and their fetuses were studied
      after 4- to 48-hour infusions of zidovudine to 14 mothers (0.8 to 2.0 mg/kg/hr)
      and 6 fetuses (0.2 to 0.22 mg/kg/hr of maternal weight). Fetal and maternal pH
      and blood gases, hematocrit, blood cell counts, clinical chemistries,
      electrolytes, and hormones were measured before and after the infusions. RESULTS:
      In both mother and fetus no significant differences were found between values in
      the control periods and those after infusions of zidovudine in any of the index
      values measured. CONCLUSION: Administration of zidovudine from 4 to 48 hours in
      the baboon was associated with no significant change in any biochemical index
      values in the mother or fetus. Thus comparable exposure of the human fetus to
      zidovudine during labor is not expected to affect these index values of placental
      function and fetal well-being.

PMID- 9166175
TI  - Do low-risk pregnant women with antiphospholipid antibodies need to be treated?
      Organizing Group of the Antiphospholipid Antibody Treatment Trial.
AB  - We identified 19 women who had persistently positive test results for
      antiphospholipid antibodies who were considered to be at low risk because they
      had none of the associated signs or symptoms of the antiphospholipid antibody
      syndrome. They had had no (10/19, 53%) or just one prior spontaneous abortion and
      did not have a history of thrombosis or thrombocytopenia. Many (8/19, 42%) had
      had a prior uncomplicated pregnancy ending in a live birth. These women were
      randomly assigned to receive low-dose aspirin (81 mg daily) or usual care. There
      were few obstetric complications recorded in either treatment group. One woman in
      the aspirin group had a fetal death, and one in the usual care group had a low
      birth-weight infant. The frequency of complications was so low that > 600 such
      women would need to be entered into a randomized trial to evaluate whether low
      dose aspirin would be beneficial treatment during a pregnancy. We concluded that
      treatment of pregnant women with antiphospholipid antibodies who are otherwise at
      low risk cannot be justified on the basis of the available evidence.

PMID- 9166176
TI  - New technologies permit safe abortion at less than six weeks' gestation and
      provide timely detection of ectopic gestation.
AB  - OBJECTIVE: The previously held dictum that elective abortion before 6 weeks'
      gestation carried greater risks than a later procedure was challenged by this
      protocol. STUDY DESIGN: This study evaluated a protocol for abortion before the
      customary 6 weeks' gestation. Patients willing to return to the clinic within 72
      hours were given the option of elective abortion even when no gestational sac
      could be visualized with transvaginal ultrasonography. When no chorionic membrane
      with villi was seen in the curettings, postoperative serum levels of beta-human
      chorionic gonadotropin confirmed complete evacuation or diagnosed ectopic
      pregnancy. RESULTS: In 1530 abortion procedures at < 6 weeks' gestation by
      ultrasonographic criteria no serious complications occurred. In addition, 9
      (0.67%) unsuspected ectopic pregnancies were diagnosed. CONCLUSIONS: Abortion
      before 6 weeks' gestation is safe, given close surveillance. Early termination
      combined with vaginal ultrasonography and follow-up with beta-human chorionic
      gonadotropin measurements allows diagnosis of early, unsuspected ectopic
      pregnancy. Ectopic pregnancy was found to be uncommon in women requesting early
      abortion.

PMID- 9166177
TI  - Polymerase chain reaction determination of RhC, Rhc, and RhE blood types: an
      evaluation of accuracy and clinical utility.
AB  - OBJECTIVE: Polymerase chain reaction amplification of a portion of the RhC/c/E/e
      gene could lead to a rapid, accurate determination of fetal RhC/c/E status. The
      purpose of this study was to evaluate the accuracy of this technique by testing
      for the first time a large number of deoxyribonucleic acid samples derived from
      individuals whose RhC/c/E status was established by standard serologic methods.
      We also evaluated the potential clinical utility of polymerase chain reaction to
      ascertain fetal antigen status. STUDY DESIGN: Samples were obtained from Centre
      d'Etude du Polymorphisme Humain families used for studies of genetic variation (n
      = 655). Deoxyribonucleic acid was extracted by standard techniques. With few
      modifications, published primers and reaction conditions were used. Samples were
      digested with restriction enzymes yielding characteristic electrophoresis
      patterns for RhC/c/E. Clinical utility was assessed by review of all patients
      evaluated for erythrocyte sensitization. RESULTS: RhC-positive (n = 479), RhC
      negative (n = 176), Rhc-positive (n = 524), Rhc-negative (n = 131), RhE-positive
      (n = 131) and RhE-negative (n = 524) samples were evaluated. The sensitivity of
      RhC/ c and E typing by polymerase chain reaction was 98.3%, 98.1%, and 96.9%,
      respectively. The specificity of polymerase chain reaction for identifying the
      RhC/c/E antigens was 91.5%, 94.7%, and 99.2%, respectively. CONCLUSIONS: Although
      it would appear that use of polymerase chain reaction to establish RhC/c/E type
      could aid in evaluation of RhC/c/E sensitization, we are concerned about the
      instances of antigen-positive individuals characterized as antigen negative.
      Further study is necessary to determine if this reflects a polymorphism,
      mutation, a data coding error, or a combination. The Centre d'Etude du
      Polymorphisme Humain database is known to contain such errors at a rate that may
      surpass the error rate of our testing. A second molecular technique could be used
      to achieve better accuracy in the ascertainment of Rh C/c/E type. On the basis of
      a review of our patient population, molecular deoxyribonucleic acid techniques
      now available could aid the management of erythrocyte sensitization in pregnancy
      in > 96% of cases.

PMID- 9166178
TI  - Three student manuals for obstetric and gynecologic outpatient care.
AB  - We have written three pocket manuals to facilitate the interaction between
      obstetric and gynecology patients and medical students, junior residents, and
      advanced practice nurses in an ambulatory care setting. The purposes of the
      manuals include the organization of the content of outpatient care into a
      consistent framework for interaction with the patient at each outpatient visit
      and the provision of a practical memory jogger to facilitate effective clinician
      patient communication. Each visit contains specific and suggested content under
      the same five categories: questions to be asked of the patient, focused aspects
      of the physical examination, laboratory tests to order, topics for purposeful
      discussion, and sentences to close the visit. These learning tools were designed
      to be integrated by local faculty into the department's formal curriculum. They
      are intended to support training in ambulatory care. They now need to be
      evaluated prospectively at individual sites.

PMID- 9166179
TI  - Nitric oxide and endothelin: paradoxes and puzzles.

PMID- 9166180
TI  - Bone loss and depot medroxyprogesterone.

PMID- 9166181
TI  - The values cannot work.

PMID- 9166182
TI  - "Head and shoulder" maneuver.

PMID- 9166183
TI  - Statistics usage in the American Journal of Obstetrics and Gynecology.

PMID- 9166184
TI  - "Abruption" and assumption.

PMID- 9166185
TI  - Complete versus partial HELLP (hemolysis, elevated liver enzymes, and low
      platelets) syndrome.

PMID- 9166186
TI  - Papillomavirus integration: prognostic marker in cervical cancer?

PMID- 9166187
TI  - Antenatal indomethacin exposure and neonatal intraventricular hemorrhage: a side
      effect or an association?

PMID- 9166188
TI  - Laparoscopic excision of endometriosis: the treatment of choice?

PMID- 9166190
TI  - Assisted conception following poor ovarian response to gonadotrophin stimulation.

PMID- 9166189
TI  - Do different brands of oral contraceptives differ in their effects on
      cardiovascular disease?

PMID- 9166191
TI  - Domestic violence and pregnancy.

PMID- 9166193
TI  - Elevated levels of serum nitrate, a stable end product of nitric oxide, in women
      with pre-eclampsia.
AB  - OBJECTIVES: Nitric oxide released from vascular endothelial cells is a potent
      vasodilator and inhibits platelet adhesion. It has been suggested that decreased
      nitric oxide production from dysfunctional endothelial cells is implicated in the
      pathophysiology of pre-eclampsia. In this study evidence was sought for abnormal
      production of nitric oxide in pre-eclamptic women. PARTICIPANTS: Blood was
      collected from 20 women presenting with pre-eclampsia, from 20 matched healthy
      pregnant controls and from 12 nonpregnant women of childbearing age. METHODS:
      Serum nitrate, the stable end metabolite of nitric oxide, was measured by
      vanadium III chloride reduction and chemiluminescence. RESULTS: Sera from women
      with pre-eclampsia had significantly higher nitrate concentrations (mean 47.4
      mumol/L [SD 13.6]) compared with healthy pregnant (mean 31.2 mumol/L [SD 9.14])
      and nonpregnant (mean 32.1 mumol/L [SD 10.0]) controls. CONCLUSIONS: These
      results do not support the hypothesis that decreased endothelial cell nitric
      oxide production may be important in the pathophysiology of pre-eclampsia. On the
      contrary, serum nitrate levels are increased which may reflect either increased
      production of nitric oxide from an unidentified source or decreased elimination
      through the kidneys.

PMID- 9166192
TI  - The effect of nifedipine and methyldopa on maternal cerebral circulation.
AB  - OBJECTIVE: To study how the treatment of severe gestational hypertension affects
      maternal middle cerebral artery velocimetry. DESIGN: Prospective, clinical,
      descriptive study. SETTING: John Radcliffe Maternity Hospital, Oxford, England.
      PARTICIPANTS: Pregnant and puerperal women who required acute or chronic
      antihypertensive treatment with nifedipine (n = 46) or methyldopa (n = 26),
      respectively. METHODS: Transcranial Doppler ultrasound examinations of maternal
      middle cerebral arteries were performed before and 45 min after nifedipine; and
      before and 48 hours after the onset of methyldopa therapy. Blood pressure and
      heart rate were also recorded. MAIN OUTCOME MEASURES: Clinical and transcranial
      Doppler changes induced by the antihypertensive medication. RESULTS: Blood
      pressure and middle cerebral artery velocities decreased significantly following
      both short- and long-acting antihypertensive therapy. Nifedipine-induced changes
      were more pronounced and uniform than those found after methyldopa (16.7% and
      6.4% decrease in middle cerebral artery mean velocity, respectively). The middle
      cerebral artery mean velocity decrease was independent of changes in the blood
      pressure or heart rate. CONCLUSIONS: Maternal cerebral haemodynamics are
      influenced by antihypertensive treatment. The reduction of middle cerebral artery
      flow velocities following administration of nifedipine and methyldopa may suggest
      that cerebral vasodilatation is occurring, which is consistent with the concept
      that cerebral vasospasm is present in women with pre-eclampsia. The cerebral
      vasodilatation could result from a direct effect of the medication on the
      arteries in question.

PMID- 9166194
TI  - External cephalic version at term: a survey of consultant obstetric practice in
      the United Kingdom and Republic of Ireland.
AB  - OBJECTIVE: To undertake a survey of external cephalic version (ECV) in the United
      Kingdom and Republic of Ireland. DESIGN: In June 1995 every consultant
      obstetrician and gynaecologist in the United Kingdom and Republic of Ireland was
      sent a postal questionnaire which asked whether ECV was routinely performed for
      breech presentation after 37 weeks of gestation, assuming no contraindications.
      If consultants did not perform ECV, a supplementary question inquired whether
      they referred patients to a colleague who would perform ECV. The questionnaires
      were colour coded for country and dispatched from the Postgraduate Education
      Department of the Royal College of Obstetricians and Gynaecologists (RCOG).
      RESULTS: Overall, 78% of questionnaires were returned. The percentage of
      consultants routinely practising ECV in each country was as follows: Northern
      Ireland 82%; Scotland 64%; Republic of Ireland 64%; England 43%; and Wales 41%.
      When these figures were compared with the latest RCOG Annual Statistical Returns
      for breech delivery and caesarean section for breech delivery, there was an
      inverse correlation between the percentage of obstetricians performing ECV in any
      one country and the incidence of breech delivery (P < 0.001). There was a similar
      inverse correlation for the percentage of obstetricians performing ECV and the
      caesarean section rate for breech delivery (P < 0.001). CONCLUSION: Although
      postal survey results are not necessarily an accurate reflection of what happens
      in clinical practice, these data are supported by evidence from the Cochrane
      Database of Systematic Reviews indicating that ECV after 37 weeks reduces the
      incidence of both breech delivery and caesarean section for breech delivery.

PMID- 9166195
TI  - Early amniotomy increases the frequency of fetal heart rate abnormalities.
      Amniotomy Study Group.
AB  - OBJECTIVE: To determine whether early amniotomy, when practised as an isolated
      intervention, increases the hourly rate of fetal heart rate record abnormalities.
      DESIGN: This is a secondary analysis of the results of a multicentre randomised
      trial of early versus late amniotomy in labour. SETTING: Secondary and tertiary
      level teaching hospitals. INTERVENTION: Early amniotomy versus an attempt to
      conserve the amniotic membranes. MAIN OUTCOME MEASURES: The hourly rates of
      early, mild variable, severe variable and late decelerations; caesarean section
      rates. RESULTS: Severe variable decelerations, when classified as categorical
      events (> or = 1/h to 2/h, > or = 2/h to < 4/h, > or = 4/h), were more frequent
      in the amniotomy group (chi2 for trend = 5.7, P = 0.017). The mean hourly rates
      of severe variable and late fetal heart rate decelerations were increased in the
      amniotomy group (severe variable: amniotomy group 1.4/h, control 0.7/h, P =
      0.021; late: amniotomy group 3.3/h, control 2.3/h, P = 0.011). Although the
      overall rate of caesarean was similar in the two groups (OR 1.2; 95% CI 0.8-1.8),
      there was an increase in caesarean section for fetal distress (OR 2.3; 95% CI 1.1
      4.5) associated with amniotomy. CONCLUSION: Our data suggest that early amniotomy
      increases the hourly rate of severe variable fetal heart rate decelerations
      without evidence of an adverse effect on neonatal outcome. In settings where the
      diagnosis of fetal compromise is based primarily on electronic monitoring,
      caesarean section for fetal distress may be increased by early amniotomy.

PMID- 9166196
TI  - Blood pressure and fetal heart rate changes with patient-controlled combined
      spinal epidural analgesia while ambulating in labour.
AB  - OBJECTIVE: To determine the effect of patient-controlled combined spinal epidural
      analgesia (PCEA) on maternal pulse and blood pressure, and fetal heart rate in
      primigravid women, when adapting different positions in labour. DESIGN: A
      prospective study. SETTING: Queen Charlotte's and Chelsea hospital, London.
      PARTICIPANTS: Fifty-five primigravid women in labour at > or = 37 weeks of
      gestation; 40 women had supervised standing top-ups given by an anaesthetist. A
      further 15 women had PCEA top-ups given in each of standing, sitting and lying
      positions. MAIN OUTCOME MEASURES: Maternal pulse rate, blood pressure and fetal
      heart rate changes following epidural top-ups. RESULTS: In the first 40 women
      there was no clinically significant fall in their blood pressure (< 5 mmHg). The
      subsequent 15 women who had PCEA top-ups had no fall in blood pressure in the
      standing and sitting positions, though the average blood pressure fell
      significantly when a top-up was given in the lying position. Maternal heart rate
      increased significantly at 12 min post top-up when the women were in the standing
      position (P = 0.0018). In the 15 women who had PCEA top-ups, the CTG showed
      improvement in decelerations when women were in the standing position but
      deterioration when in the lying position (P < 0.01). CONCLUSION: Patient
      controlled epidural analgesia top-ups with maternal mobility may be beneficial to
      the fetus possibly by reducing the hypotension normally associated with top-ups
      in the lying position.

PMID- 9166197
TI  - Automated blood pressure measurement as a predictor of proteinuric pre-eclampsia.
AB  - OBJECTIVES: To investigate the relation between antenatal clinic, obstetric day
      unit and 24-hour ambulatory blood pressure measurements and 24-hour proteinuria
      levels in hypertensive pregnancies. DESIGN: An observational study. PARTICIPANTS:
      Forty-eight women presenting with new hypertension after 20 weeks of gestation.
      RESULTS: The closest relation was found between ambulatory blood pressure
      measurements and 24-hour proteinuria levels. No significant relation was found
      between the conventional diastolic blood pressure threshold of 90 mmHg and 24
      hour proteinuria levels. CONCLUSIONS: Ambulatory blood pressure measurement gives
      better information about disease status in pre-eclampsia as assessed by
      proteinuria than does conventional sphygmomanometry.

PMID- 9166198
TI  - Third degree obstetric perineal tears: risk factors and the preventive role of
      mediolateral episiotomy.
AB  - OBJECTIVE: To determine risk factors for third degree obstetric perineal tears
      and to give recommendations for prevention. DESIGN: Retrospective case control
      study. SETTING: A teaching hospital in The Netherlands. PARTICIPANTS AND METHODS:
      One hundred and twenty cases of vaginal delivery complicated by third degree
      perineal tear and 702 uncomplicated vaginal deliveries were compared, with
      respect to possible risk factors. RESULTS: In a multivariate model high
      birthweight, forceps delivery, induced labour, epidural anaesthesia and parity
      were risk factors for anal sphincter tear. In addition, mediolateral episiotomy
      was associated with fewer sphincter injuries. Separate analysis of nulli- and
      multiparous women demonstrated that high birthweight and epidural anaesthesia
      (increased risk) and mediolateral episiotomy (decreased risk) were factors
      associated with anal sphincter tear only in nulliparous women. CONCLUSIONS: We
      found several risk factors for anal sphincter tear. Nulliparous women are at
      higher risk than multiparous women. Mediolateral episiotomy may be sphincter
      saving especially in nulliparous women and therefore prevent them from chronic
      faecal incontinence.

PMID- 9166199
TI  - Randomised trial comparing the upright and supine positions for the second stage
      of labour.
AB  - OBJECTIVE: To assess the maternal and neonatal effects of upright compared with
      recumbent positions during delivery, in terms of defined outcome variables.
      DESIGN: A randomised controlled trial. SETTING: St Monica's Nursing Home, a
      midwife based maternity unit in Cape Town, South Africa. PARTICIPANTS: Five
      hundred and seventeen women of low obstetrical risk assigned to deliver at the
      nursing home. RESULTS: The trial showed that women who adopted the upright
      posture for delivery experienced less pain. perineal trauma and fewer
      episiotomies than those who delivered in the supine position. CONCLUSION: The
      data suggest that in women of low obstetrical risk, choice of posture during
      delivery may be encouraged.

PMID- 9166200
TI  - Influence of hypertensive disorders and cigarette smoking on placental abruption
      and uterine bleeding during pregnancy.
AB  - OBJECTIVE: To assess the influence of hypertensive disorders in pregnancy on the
      subsequent risk of placental abruption and uterine bleeding of unknown aetiology,
      and to examine the combined effects of hypertensive disorders and cigarette
      smoking during pregnancy on the risk of uteroplacental bleeding disorders.
      DESIGN: Retrospective cohort study. SETTING: Data for this study were derived
      from the Nova Scotia Atlee Perinatal database, Canada, comprising of women who
      were delivered in the province between 1980 and 1993. POPULATION: 120,666
      pregnancies resulting in singleton births, of which 13,360 pregnancies were
      complicated by pre-eclampsia and/or chronic hypertension. MAIN OUTCOME MEASURES:
      Risks and relative risks of placental abruption and uterine bleeding of unknown
      aetiology in pregnancies complicated by chronic hypertension, mild and severe pre
      eclampsia, and chronic hypertension with superimposed pre-eclampsia, each
      compared with normotensive patients. Adjusted relative risks were obtained
      through the fit of multivariable logistic regression models based on the method
      of generalised estimating equations. RESULTS: Chronically hypertensive women had
      no increased risk of abruption (RR 1.4; 95% CI 0.5-3.6), while women whose
      pregnancies were complicated by severe pre-eclampsia (RR 3.8; 95% CI 2.1-6.9),
      and chronic hypertension with superimposed pre-eclampsia (RR 2.8; 95% CI 1.2-6.3)
      showed strong associations with placental abruption. However, none of the
      hypertensive disorders were associated with uterine bleeding of unknown
      aetiology. The association between placental abruption and hypertensive disorders
      varied by parity. Parous women with chronic hypertension and superimposed pre
      eclampsia were at greater risk of placental abruption (aRR 3.8; 95% CI 1.9-7.8)
      than nulliparous women with chronic hypertension and superimposed pre-eclampsia
      (aRR 1.6; 95% CI 0.5-4.9). The joint effects of smoking and hypertension had a
      greater effect on the risk of placental abruption than would have been expected
      based on their individual effects. CONCLUSIONS: The pattern of association
      between placental abruption and hypertension varied in relation to the specific
      type of hypertensive disorder. However, uterine bleeding of unknown aetiology was
      not associated with hypertension. Findings from this study suggest that placental
      abruption and uterine bleeding of unknown origin are aetiologically distinct
      obstetric complications with respect to hypertensive disorders during pregnancy.

PMID- 9166201
TI  - Epidemiology of genital prolapse: observations from the Oxford Family Planning
      Association Study.
AB  - OBJECTIVE: To explore the epidemiology of uterovaginal and post-hysterectomy
      prolapse. DESIGN: Cohort study. SETTING: Seventeen large family planning clinics
      in England and Scotland. POPULATION: 17,032 women who attended family planning
      clinics between 1968 and 1974, aged between 25 and 39 years at study entry.
      METHODS: Annual follow up by interview, postal or telephone questionnaire until
      July 1994. Further details on all hospital admissions were obtained from the
      hospital discharge summaries. All women were flagged at time of recruitment in
      the NHS central registers. MAIN OUTCOME MEASURE: In-patient admission with
      diagnosis of prolapse (ICD codes 8th Revision 623.0-623-9). RESULTS: The
      incidence of hospital admission with prolapse is 2.04 per 1000 person-years of
      risk. Age, parity, calendar period and weight were significantly associated with
      risk of an inpatient admission with prolapse after adjustment for principal
      confounding factors. Significant trends were observed with regard to smoking
      status and obesity (Quetelet Index) at entry to the study and risk of prolapse.
      Social class, oral contraceptive use and height were not significantly associated
      with risk of prolapse. The incidence of prolapse which required surgical
      correction following hysterectomy was 3.6 per 1000 person-years of risk. The
      cumulative risk rises from 1% three years after a hysterectomy to 5% 15 years
      after hysterectomy. The risk of prolapse following hysterectomy is 5.5 times
      higher (95% CI 3.1-9.7) in women whose initial hysterectomy was for genital
      prolapse as opposed to other reasons. CONCLUSION: Among the potential risk
      factors that were investigated, parity shows much the strongest relation to
      prolapse.

PMID- 9166202
TI  - The case for stopping cervical screening at age 50.
AB  - OBJECTIVE: To determine the pattern of abnormal cervical cytology in women aged
      50 to 60 years and to determine whether the development of cervical neoplasia in
      this age group is confined to women who have been inadequately screened. DESIGN:
      Retrospective case analysis study. POPULATION: An 11-year birth cohort of women
      in Grampian Region born between 2/10/33 and 1/10/44, and those who had
      significant cytological abnormalities in the 5 year period 1/10/89 to 30/9/94.
      MAIN OUTCOME MEASURES: Cytological and histological outcome for women with
      significant cytological abnormalities between 50 to 60 years of age and the
      interval between three consecutive smears taken up to 50 years of age for those
      women. RESULTS: Of 23,440 women aged 50 to 60 years ever screened in Grampian
      Region, 229 (1%) had significant cytological abnormalities. Seventy had CIN 3 and
      15 had invasive disease of the cervix. Among approximately 9000 women with
      adequate smear histories prior to age 50, one case of CIN 3 and one case of
      invasion were detected. The prevalence of invasive disease in the whole cohort
      during this five year period was 59/100,000. Among the previously well screened
      women the prevalence was 11/100,000. CONCLUSION: The incidence of preinvasive
      disease of the cervix is low over the age of 50 and is seen almost exclusively in
      inadequately screened women. There would appear to be little benefit in
      continuing cervical screening over the age of 50 in women who have had regular
      negative smears. The release of this low risk group from the cervical screening
      programme could alleviate anxiety and could enable reallocation of resources to
      target better high risk women who default from regular screening and to reduce
      screening intervals where necessary to three years.

PMID- 9166203
TI  - Randomised trial of immediate versus deferred treatment strategies for the
      management of minor cervical cytological abnormalities.
AB  - OBJECTIVE: To compare immediate and deferred treatment in women with cervical
      smears showing borderline nuclear abnormalities or mild dyskaryosis. DESIGN:
      Prospective randomised trial. SETTING: Colposcopy clinics at Birmingham and
      Midland Hospital for Women and the City Hospital NHS Trust, Dudley Road,
      Birmingham. PARTICIPANTS: Four hundred and thirty-five women with minor
      cytological abnormality younger than 35 years of age, of whom 353 were randomised
      to immediate treatment or deferred treatment. MAIN OUTCOME MEASURES: Comparison
      of histologies in the subsequent two years in the immediate and deferred
      treatment groups. RESULTS: Thirty-six women (21%) defaulted from follow up. The
      percentage of high grade abnormalities (CIN II and III) in the deferred treatment
      arm at two years is similar to that in the immediate treated arm at first
      colposcopy (25% vs 24%). Cytology failed to pick up two cases of CIN III and
      there was one case of early invasive carcinoma at the six month follow up. If
      treatment is deferred, the proportion with CIN I is almost halved (25% vs 13%);
      the proportion with koilocytic atypia is slightly reduced (51% vs 42%) and the
      proportion with no abnormality is substantially increased (0.6% vs 20%).
      CONCLUSION: Immediate referral and a select-and-treat management strategy of all
      women with any degree of dyskaryosis is recommended based on the case of invasive
      cervical cancer, high default rate and the failure of cytology to pick up two
      cases of CIN III.

PMID- 9166204
TI  - Complications of laparoscopy: a prospective multicentre observational study.
AB  - OBJECTIVE: To determine the incidence and describe the complications of
      laparoscopic procedures in The Netherlands. DESIGN: A nationwide prospective
      multicentre observational study. METHODS: Data on complications were registered
      from 1 January to 31 December 1994 by 72 hospitals. Any unexpected or unplanned
      event requiring intra-operative or post-operative intervention was defined as a
      complication. Complications were classified in two groups: approach and technique
      related complications. Complication rates were compared with these already
      published. RESULTS: Of 25,764 laparoscopic procedures, 145 complications occurred
      (rate 5.7 per 1000 [/1000]); two deaths occurred. In 84 women laparotomy was
      necessary (rate 3.3/1000). In 83 cases (57%; 95% CI for approach = 49-65%) the
      complication was caused by the surgical approach; in 62 cases (43%) the technique
      was at fault. Haemorrhage of the epigastric vein and intestinal injury, often
      requiring laparotomy (90% of cases) were the most frequently observed
      complications. The complication rate was 2.7/1000 for diagnostic laparoscopic
      procedures, 4.5/1000 for sterilisation and 17.9/1000 (chi 2 = 127; dF = 2; P <
      0.001) for operative laparoscopy. The highest incidence was registered for
      complications occurring during laparoscopic (assisted) hysterectomy. Stepwise
      logistic regression analysis showed that previous laparotomy and surgical
      experience were associated with complications requiring laparotomy. CONCLUSIONS:
      Most complications occurred during operative laparoscopic procedures (rate
      17.9/1000). Residents in training are required to learn diagnostic laparoscopy
      and sterilisation and this training programme results in a fall in the risk of
      the complications. However, operative laparoscopic procedures are still
      hazardous, especially laparoscopic hysterectomy. Women with a previous laparotomy
      are particularly at risk.

PMID- 9166205
TI  - A pragmatic randomised comparison of transcervical resection of the endometrium
      with endometrial laser ablation for the treatment of menorrhagia.
AB  - OBJECTIVE: To compare endometrial laser ablation (ELA) with transcervical
      resection of the endometrium (TCRE) in the treatment of menorrhagia. DESIGN:
      Randomised controlled trial. SETTING: Gynaecology department of a large teaching
      hospital. PARTICIPANTS: Women with menorrhagia due to dysfunctional uterine
      bleeding (n = 372) were randomly allocated to ELA (n = 188) or TCRE (n = 184).
      MAIN OUTCOME MEASURES: Operative complications, post-operative recovery, relief
      of menstrual and other symptoms, need for further surgical treatment,
      satisfaction with treatment after 6 and 12 months, and differential resource use.
      RESULTS: TCRE was significantly quicker, with lower rates of fluid overload.
      Perioperative morbidity was low and similar in both groups. Outcome at 12 months
      was also similar: 72 women (45%) had either amenorrhoea or brown discharge in the
      ELA group compared with 71 (49%) in the TCRE group; 79 (49%) versus 68 (46%) had
      lighter periods. Thirty (16%) versus 36 (20%) had received further surgical
      treatment: 9 (5%) compared with 25 (14%) had had a hysterectomy and 21 (11%)
      versus 11 (6%) had received repeat ablation. Anxiety and depression,
      dysmenorrhoea and pre-menstrual symptoms were improved by both procedures and
      bladder symptoms were affected by neither. At 12 months 148 (90%) women in the
      ELA group and 140 (91%) women in the TCRE group were satisfied with their
      treatment. The estimated additional cost of ELA was Pound 145 per procedure.
      CONCLUSIONS: At one year there was no clear difference in clinical outcome
      between ELA and TCRE. Both procedures were associated with low morbidity. ELA was
      the more costly procedure. Despite the need for further surgery for about one in
      six women, satisfaction rates were high following both ELA and TCRE.

PMID- 9166206
TI  - Radiofrequency induced endometrial ablation: an update.
AB  - OBJECTIVE: To test the safety and efficiency of radiofrequency endometrial
      ablation as a nonhysteroscopic treatment of dysfunctional uterine bleeding.
      DESIGN: A multicentre trial. SETTING: Nineteen clinics in six countries. METHODS:
      From February 1990 to December 1994, 1280 women were treated with radiofrequency
      endometrial ablation. Inclusion criteria were: menorrhagia, age 30-55 years, a
      completed family, a wish to retain the uterus, no hypergonadotropic state
      indicating an approaching menopause, a normal sized uterus, normal cervical
      cytology, normal adnexa, no prolapse, no intrauterine abnormalities, and no
      history of a bleeding disorder. Treatment was performed according to a standard
      operating protocol. RESULTS: Either amenorrhoea or a satisfactory improvement of
      menstruation was obtained in 78.5% of 944 women followed for six months or more.
      The design of the equipment has been thoroughly revised and improved during the
      last four years. The complications encountered were mostly related to the
      handling of radiofrequency and sometimes due to failures in following the safety
      protocol. CONCLUSIONS: Although the technology is complicated, the treatment is
      simple, fast and effective. The complications have often been unpredictable.
      Despite the improvements made during this period, safety must be further enhanced
      to develop the original concept into an established technique.

PMID- 9166207
TI  - The levonorgestrel intrauterine system in the management of menorrhagia.
AB  - OBJECTIVE: To assess the effect of a levonorgestrel releasing intrauterine system
      in the management of menorrhagia. DESIGN: A prospective study. SETTING: A
      district general hospital in South Wales. METHODS: Fifty women with a failed
      trial of medical therapy and awaiting hysterectomy or transcervical resection of
      the endometrium (TCRE) were treated with a levonorgestrel intrauterine system.
      The menstrual loss was estimated using a modified pictorial chart together with a
      full blood count and ferritin measurement preinsertion and at three and six to
      nine months postinsertion. RESULTS: The menstrual loss was reduced to acceptable
      levels in 37 women at three months and a further four by six to nine months. In
      all, 41 patients were taken off the waiting list for surgery, four of whom became
      amenorrhoeic. There was no significant change in full blood count nor ferritin
      measurement despite unscheduled bleeding for six to eight weeks postinsertion.
      Fifty-six percent of patients noticed considerable improvement or cure of their
      premenstrual syndrome symptoms; 80% noted a reduction in dysmenorrhoea.
      CONCLUSION: The levonorgestrel releasing intrauterine system is an effective
      nonsurgical treatment for the management of menorrhagia and dysmenorrhoea that
      has additional benefit as a contraceptive and in relieving premenstrual syndrome.

PMID- 9166208
TI  - Female victims of rape and their genital injuries.
AB  - OBJECTIVE: A minority (some report < 10%) of women report sexual assault. Of
      those that negotiate the police process, only a minority will come to a court
      hearing. It is thought that the courts still rely upon medical evidence, in
      particular evidence of genital injury to 'prove' the rape. This study aimed to
      ascertain the incidence of genital injury in victims of alleged rape. DESIGN:
      Retrospective review of case records of women who reported they had had been
      raped, provided by women doctors on the Northumbrian Police Doctors scheme.
      SAMPLE: Case records from Newcastle, North and South Tyneside, Sunderland and
      Northumbria. METHODS: Analysis of records in the standardised booklet used by
      police surgeons to examine women reporting rape. MAIN OUTCOME MEASURES: Presence
      of genital injury, presence of other physical injuries. RESULTS: A minority of
      women had genital injuries (22/83); the majority had some form of physical injury
      (68/83), although most of these were minor. CONCLUSION: The study shows that only
      a minority of women examined by specifically trained police doctors show evidence
      of genital injury. The absence of genital injury does not exclude rape.

PMID- 9166209
TI  - Vaginal endoscopic oophorectomy with vaginal hysterectomy: a simple minimal
      access surgery technique.
AB  - The main advantage of laparoscopic assisted vaginal hysterectomy (LAVH) is ease
      of access to the ovaries; despite this, LAVH is infrequently performed due to the
      inherent difficulty of the technique. Lower morbidity, shorter length of surgery,
      reduced hospital stay and more rapid recovery are the main advantages of vaginal
      hysterectomy, but one of its limitations is the accessibility of the ovaries.
      Three methods of vaginal endoscopic oophorectomy following vaginal hysterectomy
      are described in this paper. Endoscopic vaginal oophorectomy was successfully
      performed during 82 cases of vaginal hysterectomy and the results show that the
      technique is simple, safe and easy to learn, and an alternative to laparotomy and
      LAVH in the absence of pelvic adhesions.

PMID- 9166210
TI  - Ploidy profile of morphologically normal squamous epithelium adjacent to high
      grade cervical intraepithelial neoplasia.
AB  - We have investigated the ploidy profile of morphologically normal mucosa adjacent
      to high grade CIN (n = 16) and also from normal cervix (n = 18). DNA ploidy was
      assessed using flow cytometry and image analysis. All cases were diploid by both
      modalities. Our results show that morphologically normal squamous mucosa has a
      stable ploidy profile even when it lies adjacent to high grade CIN. This finding
      supports the view that high grade CIN is a neoplastic expansion of transformed
      cells rather than the result of a field change effect.

PMID- 9166211
TI  - Selective termination by intrahepatic vein alcohol injection of a monochorionic
      twin pregnancy discordant for fetal abnormality.

PMID- 9166212
TI  - Successful methotrexate treatment of a viable pregnancy within a thin uterine
      scar.

PMID- 9166213
TI  - Familial puerperal alactogenesis: possibility of a genetically transmitted
      isolated prolactin deficiency.

PMID- 9166214
TI  - A prospective study to evaluate oophorectomy at the time of vaginal hysterectomy.

PMID- 9166215
TI  - Magnesium sulphate: the time for reckoning.

PMID- 9166216
TI  - Lack of analgesic effect of systemically administered morphine or pethidine on
      labour pain.

PMID- 9166217
TI  - A prospective cohort study of oxytocin plus ergometrine compared with oxytocin
      alone for prevention of postpartum haemorrhage.

PMID- 9166218
TI  - Oral versus vaginal misoprostol for cervical priming.

PMID- 9166219
TI  - Electrospray mass spectrometry for measurement of glycohemoglobin.

PMID- 9166220
TI  - Telomeres and telomerase: biological and clinical importance.
AB  - We review the present knowledge of telomeres and telomerase with special
      attention to their role in cell proliferation, cellular senescence, and human
      aging. We summarize the functional aspects of telomerase in cancer, as well as
      its role as a useful diagnostic and prognostic tumor marker, and discuss possible
      approaches to telomerase inhibition as a target for cancer therapy.

PMID- 9166221
TI  - Development of enzyme immunoassay for endogenous ouabain-like compound in human
      plasma.
AB  - Widespread evidence supports the existence of an endogenous digitalis-like
      compound in mammals. We report here the development of a novel enzyme immunoassay
      for ouabain that, in conjunction with a detailed HPLC study, identifies a ouabain
      like compound (OLC) in extracted human plasma. The assay is sensitive-minimum
      detection limit for OLC 37 pmol/L (11 pmol/L in plasma)-and has a working range
      (between-assay CV < 10%) of 180-10000 pmol/L (54-3000 pmol/L in plasma). Mean
      recoveries of ouabain added to plasma ranged from 90% to 100%, and plasma
      extracts diluted in parallel to the standard curve. Plasma OLC concentrations in
      10 healthy volunteers averaged 92 pmol/L (range 55-168), assuming 100% cross
      reactivity of OLC in the ouabain assay. HPLC analysis with two distinct
      chromatographic conditions demonstrated that endogenous human plasma OLC co
      eluted with authentic ouabain. The enzyme immunoassay is rapid and easy to
      perform and will support further investigation of the nature of this
      controversial endogenous steroid.

PMID- 9166222
TI  - Exhaled human breath measurement method for assessing exposure to halogenated
      volatile organic compounds.
AB  - The organic constituents of exhaled human breath are representative of blood
      borne concentrations through gas exchange in the blood/breath interface in the
      lungs. The presence of specific compounds can be an indicator of recent exposure
      or represent a biological response of the subject. For volatile organic compounds
      (VOCs), sampling and analysis of breath is preferred to direct measurement from
      blood samples because breath collection is noninvasive, potentially infectious
      waste is avoided, and the measurement of gas-phase analytes is much simpler in a
      gas matrix rather than in a complex biological tissue such as blood. To exploit
      these advantages, we have developed the "single breath canister" (SBC) technique,
      a simple direct collection method for individual alveolar breath samples, and
      adapted conventional gas chromatography-mass spectrometry analytical methods for
      trace-concentration VOC analysis. The focus of this paper is to describe briefly
      the techniques for making VOC measurements in breath, to present some specific
      applications for which these methods are relevant, and to demonstrate how to
      estimate exposure to example VOCs on the basis of breath elimination. We present
      data from three different exposure scenarios: (a) vinyl chloride and cis-1,2
      dichloroethene from showering with contaminated water from a private well, (b)
      chloroform and bromodichloromethane from high-intensity swimming in chlorinated
      pool water, and (c) trichloroethene from a controlled exposure chamber
      experiment. In all cases, for all subjects, the experiment is the same:
      preexposure breath measurement, exposure to halogenated VOC, and a postexposure
      time-dependent series of breath measurements. Data are presented only to
      demonstrate the use of the method and how to interpret the analytical results.

PMID- 9166223
TI  - Detection of anabolic steroid administration: ratio of urinary testosterone to
      epitestosterone vs the ratio of urinary testosterone to luteinizing hormone.
AB  - Our goal in this study was to determine whether the urinary ratio of testosterone
      to luteinizing hormone (T/LH) as an indicator of exogenous anabolic steroid (AS)
      use is superior to the urinary ratio of testosterone to epitestosterone (T/E).
      After 2 weekly placebo injections, 19 subjects were given testosterone cypionate
      (TC) injections of 250 or 500 mg/week for 14 weeks followed by 14 weekly placebo
      injections. Patients were considered to have ceased taking TC if they tested
      negative 9 weeks after their last injection. For detection of illicit or
      supraphysiological TC (AS) use, the urinary T/E ratio of > or = 6 yielded a false
      negative rate of 46% and a false-positive rate of 4%. However, a urinary T/LH
      ratio of > or = 30 produced a false-negative rate of only 24% and a false
      positive rate of 13%. We conclude that the urinary T/LH ratio of > or = 30 is a
      more sensitive marker of AS use than the urinary T/E ratio of > or = 6 and
      remains sensitive for twice as long as urinary T/E.

PMID- 9166224
TI  - Sweat testing for heroin and metabolites in a heroin maintenance program.
AB  - Recent advances in sensitive analytical techniques have enabled the analysis of
      drugs in unconventional biological materials such as sweat. In a study conducted
      during a heroin maintenance program, 14 subjects had sweat patches applied, then
      received intravenously two or three doses of heroin hydrochloride ranging from 80
      to 1000 mg/day. The sweat patch was applied 10 min before the first dosage and
      removed approximately 24 h later, minutes before the next dosage. Absorbent pads
      were stored at -20 degrees C in plastic tubes until analysis. The target drugs
      were extracted in 5 mL of acetonitrile in the presence of 100 ng each of heroin
      d9, 6-acetylmorphine-d3, and morphine-d3. After agitation for 30 min, the
      acetonitrile solution was divided into two portions: 2 mL for heroin testing and
      the remainder for testing for the other compounds. After evaporation, the residue
      of the first portion was reconstituted in 35 microL of acetonitrile; the second
      was derivatized by silylation with 40 microL of N,O
      bis(trimethylsilyl)trifluoroacetamide containing 10 mL/L trimethylchlorosilane.
      Drugs were analyzed by GC-MS in electron impact mode. Concentrations (nanograms
      per patch) ranged from 2.1 to 96.3 for heroin, 0 to 24.6 for 6-acetylmorphine,
      and 0 to 11.2 morphine. Except in one case, heroin was the major drug present in
      sweat, followed by 6-acetylmorphine and morphine. We observed no correlation
      between the doses of heroin administered and the concentrations of heroin
      measured in sweat.

PMID- 9166225
TI  - Microdialysis-HPLC for plasma levodopa and metabolites monitoring in parkinsonian
      patients.
AB  - We used in vitro microdialysis-HPLC to determine L-3,4-dihydroxyphenylalanine (L
      DOPA) and its metabolites in plasma of patients with advanced Parkinson disease.
      Blood samples and clinical evaluations were obtained 0, 30, 60, 90, 120, and 150
      min after oral administration of carbidopa/L-DOPA (25/100 mg, 12.5/125 mg, and
      50/200 mg). In vitro recoveries for L-DOPA and metabolites ranged from 22% to
      36%. Linear correlation was found between metabolite concentrations in the
      dialysate and in the surrounding medium. There was a significant positive
      correlation between L-DOPA dose and plasma concentration of L-DOPA and
      homovanillic acid (P < 0.04). Clinical response was maximum 60 min after L-DOPA
      administration. Threshold L-DOPA plasma concentration averaged 7.74 +/- 3.3
      mumol/L. Motor effect is longer with the highest L-DOPA peak concentration (P <
      0.01). Microdialysis-HPLC is readily applicable, reproducible, and allows
      monitoring of plasma L-DOPA and metabolites in parkinsonian patients.

PMID- 9166226
TI  - Diagnosis of Duchenne/Becker muscular dystrophy and quantitative identification
      of carrier status by use of entangled solution capillary electrophoresis.
AB  - Use of capillary electrophoresis, a new and useful analytical tool, offers a
      variety of advantages for nucleic acid analyses, including rapid analysis,
      automation, high resolution, qualitative and quantitative results, and low
      consumption of both sample and reagents. We report the first example of the use
      of entangled solution capillary electrophoresis (ESCE) and laser-induced
      fluorescence detection (LIF) for separation-based diagnostics in the quantitative
      analysis of multiplex PCR products for determination of carrier status of
      Duchenne/ Becker muscular dystrophy (DMD/BMD). This approach greatly improved the
      speed, resolution, and sensitivity of information needed for the diagnosis of
      DMD/BMD compared with that from conventional diagnostic methods, and is of
      general utility for diagnosis of genetic diseases.

PMID- 9166227
TI  - Quantitative polymerase chain reaction-based homogeneous assay with fluorogenic
      probes to measure c-erbB-2 oncogene amplification.
AB  - We describe a PCR-based assay for determining c-erbB-2 oncogene amplification in
      breast cancer in which we use the TaqMan system. Two fluorogenic probes anneal to
      the target between primers for c-erbB-2 and beta-globin genes and contain both a
      reporter dye (6-carboxy-fluorescein) and a quencher dye (6-carboxy-tetramethyl
      rhodamine). During the extension phase of the PCR cycle, the 5'-->3' exonuclease
      activity of Taq polymerase cleaves the hybridized fluorogenic probe, resulting in
      an increase of fluorescence emission of the reporter dye that is quantitative for
      the amount of PCR product and, under appropriate conditions, for the amount of
      template. Assay performance showed adequate precision and a lower detection limit
      and good correlation with the results obtained in the same samples by a
      competitive PCR assay (n = 25, r = 0.94, P < 0.01). This homogeneous assay is
      time-saving, avoids usually cumbersome postamplification procedures (that can be
      additional sources of inaccuracy and contamination), and seems suitable for
      determination of c-erbB-2 oncogene amplification in tumor specimens.

PMID- 9166228
TI  - Analysis of a polyadenine tract of the transforming growth factor-beta type II
      receptor gene in colorectal cancers by non-gel-sieving capillary electrophoresis.
AB  - We developed a method to analyze a polyadenine tract, the (A)10 repeat, within
      the cysteine-rich domain of the transforming growth factor-beta (TGF-beta) type
      II receptor gene using a non-gel-sieving capillary electrophoresis technique and
      applied it to the DNA diagnosis of colorectal cancers. This method consists of
      single-strand DNA amplification of the (A)10 repeat by an asymmetric PCR
      technique and capillary electrophoresis. A higher concentration of dATP in the
      PCR reaction mixture led to more specific amplification of the (A)10 repeat.
      Under the optimal electrophoretic conditions, one nucleotide difference could be
      determined in 8 to 32 nucleotides. One or two base deletions of the (A)10 repeat
      in colorectal cancers could be detected under these conditions within 30 min, and
      the results coincided with those obtained on DNA sequencing analyses. According
      to a sensitivity study, we could detect the deleted sequence if it was present in
      12.5% or more of the wild-type allele. The reproducibility of this technique was
      satisfactory because the intraassay imprecision (CV) (n = 10) was 1.4%. These
      results indicate that capillary electrophoretic analysis of small repeated
      sequences results in easier handling and more feasible automation, compared with
      conventional gel electrophoretic analysis.

PMID- 9166229
TI  - Construction of cDNA bank from biopsy specimens for multiple gene analysis of
      cancer.
AB  - We constructed a "cDNA bank" of human colorectal cancer and surrounding normal
      tissues with our unique mRNA assay system. Total nucleic acids extracted from
      patients' tissues were applied to 96-well plates, where poly(dT) sequences of
      oligonucleotides were immobilized. After hybridization, the cDNA was reverse
      transcribed on the plate with the captured mRNA as a template, followed by
      synthesis of double-stranded (ds) cDNA. The resulting sense cDNA was removed from
      the plate, then used in PCR for analysis of various genes. The sense strand of
      the cDNA was repeatedly synthesized by using the immobilized antisense cDNA as a
      template even from plates used once and stored at 4 degrees C for as long as 6
      months. Furthermore, the results of PCR could be easily compared among different
      specimens if the same amount of total mRNA were applied to the plate for the ds
      cDNA synthesis. This demonstrated that the cDNA bank constructed from clinical
      materials provides almost unlimited supplies of cDNA for multiple gene analysis
      of cancer.

PMID- 9166230
TI  - Potential of electrospray mass spectrometry for quantifying glycohemoglobin.
AB  - An electrospray ionization-mass spectrometric procedure has been developed for
      determining glycohemoglobin. Whole-blood samples from 78 diabetic and 50
      nondiabetic subjects (glycation range 3-15%, as determined by electrospray mass
      spectrometry) were diluted 500-fold in an acidic denaturing solvent and
      introduced directly into a mass spectrometer. The resulting mass spectra were
      then processed to estimate the percentage of glycohemoglobin present in the
      sample. Total analysis time, including plotting the spectra and computing the
      percentage of glycation, was approximately 3 min. The imprecision (CV) of the
      method was < 5.1% for inter- and intrabatch analyses for total glycohemoglobin in
      the range 3.6-14%. Comparison of the mass spectrometric results with those from
      established affinity chromatographic procedures showed good overall agreement.
      The relative glycation of the alpha- and beta-chains was determined directly and
      was shown to be constant (0.64:1) over the glycation range measured. Only single
      glucose attachment to both the alpha- and beta-chains was observed.

PMID- 9166231
TI  - Measurement of antibodies against glutamic acid decarboxylase 65 (GADA): two new
      125I assays compared with [35S]GAD 65-ligand binding assay.
AB  - Recently, 65-kDa glutamic acid decarboxylase (GAD 65) antibodies (GADA) have been
      introduced as autoimmune markers in blood to confirm the diagnosis of insulin
      dependent diabetes mellitus (IDDM). In this study, to evaluate two new assays
      that use 125I-labeled GAD 65, we assayed samples from 100 children with recent
      onset of diabetes and 100 control children, the results were compared with those
      of a [35S]GADA assay and with results for islet cell antibodies (ICA), the
      conventional autoimmune marker. Receiver operating characteristic (ROC) curve
      analysis showed one of the new assays (from RSR) to be more sensitive (P = 0.01)
      than the comparison ([35S]GADA) assay, whereas the second new assay (from Elias)
      was less sensitive (P < 0.001). The GADA frequency at 97.5% specificity was
      greatest in the comparison assay: 63 of 100 vs 41 of 100 (P < 0.01) and 53 of 100
      (P = 0.16) in the RSR and Elias assays, respectively. Almost all GADA-positive
      patients had ICA, but one-third of the ICA-positive patients was GADA-negative.
      Accordingly, adding GADA analysis results to ICA testing increased the frequency
      of detection of autoimmune markers only slightly (from 81% to 85%). In
      conclusion, at 97.5% specificity the [35S]GADA assay seemed to be more efficient
      than the 125I assays, although the difference was significant only for the Elias
      125I assay. Antigen-specific antibodies other than GADA may explain the
      difference in GADA and ICA frequencies.

PMID- 9166232
TI  - Convenient chromatographic prepurification step before measurement of urinary
      cortisol by radioimmunoassay.
AB  - We applied various prepurification protocols (extraction with different solvents,
      liquid/solid separation on bonded silica media, Celite, and Sephadex LH20
      chromatography) with a range of commercially available RIA kits to measure
      cortisol in urine samples. We then compared the results with the concentrations
      measured by a HPLC method validated with reference to isotope dilution gas
      chromatography-mass spectrometry. We conclude that chromatography on a
      commercial, prepacked diol minicolumn (Waters Sep-Pak Vac RC) in combination with
      dichloromethane extraction is a convenient and very effective purification step
      before RIA of urinary cortisol in patients not receiving corticoid medication. We
      tested numerous steroids for interference and found that free polar cortisol
      derivatives (hydroxylated or hydrogenated) could only partially account for the
      overestimations routinely encountered when free urinary cortisol concentrations
      are measured by direct RIA.

PMID- 9166233
TI  - Accurate and precise isotope dilution mass spectrometry method for determining
      glucose in whole blood.
AB  - An accurate and precise method to determine glucose concentration in whole blood
      is presented. The method, based on isotope dilution gas chromatography-mass
      spectrometry (ID GC-MS), was developed to be used as a Reference Method for
      determining glucose concentration in capillary or venous whole blood. Blood
      samples and standards are pipetted manually with "microcap" micropipettes, which
      makes it possible to collect samples even at the patient's bedside. Glucose is
      quantified as its aldononitrile pentaacetate. [13C6]Glucose is used as an
      internal standard. Assay of Seronorm and Pathonorm L and H controls by ID GC-MS
      gave within-run CVs of 0.66%, 0.96%, and 0.92%, respectively. For whole blood
      with glucose concentrations in the low, normal, and high ranges, the within-run
      CVs were 1.27%, 0.91%, and 0.78%, respectively. The between-run CV for glucose
      calculated from 36 separate single analyses of Seronorm was 1.44%. In an accuracy
      assessment test of the HemoCue blood glucose analyzer, 140 capillary blood
      samples were measured in parallel after split-sampling. For all samples the
      HemoCue analyzer results had a mean bias of +2.0% compared with the ID GC-MS
      results.

PMID- 9166234
TI  - Automation of human sperm cell analysis by flow cytometry.
AB  - Semen sample analysis is routinely performed by microscopical evaluation and
      manual techniques by laboratory operators; the analysis is affected by a wide
      imprecision related to variability among observers, influencing its clinical
      validity. Our aim was to automate sperm analysis with the use of flow cytometry
      for evaluation of cell counts and typing and with the use of a new membrane
      permeant nucleic acid stain for evaluation of sperm viability. Statistical
      analysis of the comparison between manual and automated methods for sperm counts
      was performed by the Bland and Altman method; the mean difference was 0.243 x
      10(6) sperms/ mL. The precision of the flow cytometric analysis was evaluated
      with whole sperm; the between-run CV was 7.5% and the within-run CV was 2.5%.
      Data observed suggest that flow cytometric sperm analysis, with high precision
      and accuracy and low costs, can be proposed for routine use in clinical
      laboratories.

PMID- 9166235
TI  - Calculation of LDL-cholesterol by using apolipoprotein B for classification of
      nonchylomicronemic dyslipemia.
AB  - In this paper we propose a calculation of LDL-cholesterol (LDL-C) not affected by
      hypertriglyceridemia by using lipid quantities directly measured in total serum.
      We also propose an algorithm for the classification of nonchylomicronemic
      dyslipemias. Plasma apolipoproteins (apo) A-I, B, total cholesterol (TC),
      triglycerides (TG), and cholesterol of lipoproteins were measured in a group of
      38 normolipemic and 120 dyslipemic patients (42 phenotype IIa, 38 IIb, and 40 IV)
      classified according to TG and LDL-C values. Discriminant analysis was applied to
      obtain the best classification with the lowest number of quantities directly
      measured from total serum (TC, TG, and apo B), and multiple regression analysis
      was performed to find an equation to calculate LDL-C from these quantities. Apo B
      seems to be a useful discriminator between normolipemic and phenotype IIa
      patients, by using a cutoff value of 1.35 g/L obtained by ROC curve analysis. The
      proposed algorithm, based on lipid quantities measured by easily automated
      methods, is shown to be a good alternative for the classification of
      nonhyperchylomicronemic dyslipemia. LDL-C calculated from TC, TG, and apo B
      proved a better estimate of true LDL-C than the estimate obtained with
      Friedewald's formula.

PMID- 9166236
TI  - Three generations of high-density lipoprotein cholesterol assays compared with
      ultracentrifugation/dextran sulfate-Mg2+ method.
AB  - We report on the analytical performance of three generations of HDL-cholesterol
      assays: phosphotungstic acid/Mg2+, Spinpro, and a homogeneous method, N-geneous.
      The run-to-run imprecision (CV) of all assays was < or = 4.9%, and all results
      correlated highly with those of a modified reference procedure (r > or = 0.96).
      At triglycerides concentrations < 4000 mg/L, these field methods showed an
      acceptable systematic error (y = 1.12x - 47, 1.05x - 23, and 0.96x + 8 for the
      phosphotungstate, Spinpro, and N-geneous assays, respectively), and the total
      error of the field methods met the current National Cholesterol Education Program
      (NCEP) performance goal of < or = 22%. Regression analyses of results for samples
      with triglycerides > 4000 mg/L produced the following results for the above
      respective assays: y = 1.08x - 4.2, 1.02x + 3.6, and 0.85x + 108. In this
      hypertriglyceridemic group, only the N-geneous assay (at an HDL-cholesterol
      content of 240 mg/L) had a total error (35%) that exceeded the NCEP limit.
      Bilirubin and ascorbate produced a negative interference with the
      phosphotungstate and Spinpro assays but had little effect on the N-geneous assay.

PMID- 9166237
TI  - Modified and improved anti-acetylcholine receptor (AchR) antibody assay:
      comparison of analytical and clinical performance with conventional anti-AChR
      antibody assay.
AB  - We developed a modified anti-acetylcholine receptor (AChR) antibody (Ab) assay
      based on a radioreceptor assay and a calibration curve. We compared the
      analytical and clinical performances of this modified assay with those of the
      conventional anti-AChR Ab radioreceptor assay. Serum specimens were from patients
      with myasthenia gravis (MG) (n = 156) and from control subjects (n = 106). The
      modified assay demonstrated lower within-assay (4.0-6.6%) and between-assay (5.3
      7.8%) CVs, greater linearity, lower cost, and shorter assay time than the
      conventional method. ROC curve analysis indicated almost identical specificity
      and sensitivity (> 0.92) for these two anti-AChR Ab assays. The modified and
      conventional assays were also equivalent for blocking anti-AChR Ab assay.
      Moreover, the modified anti-AChR Ab assay, differently from the conventional
      assay, allowed us to reveal anti-AChR Ab concentration differences among
      different clinical grades of MG.

PMID- 9166238
TI  - Evaluation of a rapid, new method for detecting serum IgG antibodies to
      Helicobacter pylori.
AB  - There is an increased need for rapid, inexpensive tests to diagnose Helicobacter
      pylori infection. Our objective was to determine the performance characteristics
      of an immunochromatographic test (ICT) for detection of anti-H. pylori IgG
      antibodies. A commercially available ICT kit (FlexSure HP) was tested with a well
      characterized cohort of banked sera as well as with fresh serum from randomly
      selected symptomatic patients. The ICT was evaluated with 107 stored sera and 96
      prospective patients. The test correctly identified 65 of 68 H. pylori-infected
      and 37 of 39 noninfected stored sera and 54 of 57 infected and 30 of 39
      noninfected patients. Sensitivity, specificity, and positive and negative
      predictive values were 96%, 95%, 97%, and 93% in stored serum and 95%, 77%, 86%,
      and 91% in fresh serum, respectively. We concluded that the ICT, reported at 4
      min, is highly sensitive for detecting anti-H. pylori IgG antibodies in human
      serum. With a high negative predictive value, the test may be used to exclude H.
      pylori infection in symptomatic patients.

PMID- 9166239
TI  - Gastric tubes, meals, acid, and analysis: rise and decline.
AB  - The stomach tube was first used to administer food and medication or to remove
      poisonous substances. Later, it served to aspirate the stomachs of patients with
      gastric retention. Chemical analysis of stomach contents after a meal was first
      suggested in 1871 and quickly became an important laboratory procedure as various
      test-meal stimuli and more flexible tubes were developed. Quantitative
      estimations of free and total acidity were made by titration with 0.01 mol/L
      sodium hydroxide and specific indicators. Pentagastrin has supplanted
      secretagogues such as histamine and betazole; meal stimulation, tubeless tests,
      and other tests of gastric secretion are no longer used clinically. Tests of
      gastric acid secretion have been used in the diagnosis of upper gastrointestinal
      lesions and to help select the type of surgical procedure for gastric and
      duodenal ulcers, but the tests have decreased in importance because of their
      limited diagnostic sensitivity and specificity. Today, fiberoptic endoscopy is
      replacing gastric analysis as well as radiologic examination.

PMID- 9166240
TI  - Five PSA methods compared by assaying samples with defined PSA ratios.

PMID- 9166241
TI  - Changes in plasma metallothionein-1, interleukin-6, and C-reactive protein in
      patients after elective surgery.

PMID- 9166242
TI  - Immunoreactive prostate-specific antigen in pleural effusions.

PMID- 9166243
TI  - Rapid method for detection of anti-recombinant human erythropoietin antibodies as
      a new form of erythropoietin resistance.

PMID- 9166244
TI  - Isoflavone content of breast milk and soy formulas: benefits and risks.

PMID- 9166245
TI  - Isoflavone content of breast milk and soy formulas: benefits and risks.

PMID- 9166246
TI  - Isoflavone content of breast milk and soy formulas: benefits and risks.

PMID- 9166247
TI  - Measurement of individual vs total antioxidants.

PMID- 9166248
TI  - Prostate-specific antigen in cerebrospinal fluid.

PMID- 9166249
TI  - Reduced serum antioxidant capacity in healthy centenarians.

PMID- 9166250
TI  - The smallest concentration.

PMID- 9166251
TI  - Polymorphonuclear elastase and interleukin-6 in amniotic fluid in preterm labor.

PMID- 9166252
TI  - Point-of-care testing and length of stay.

PMID- 9166254
TI  - Quality for tomorrow: by design or by checking?

PMID- 9166253
TI  - Prevention of analytical false-positive increases of cardiac troponin I on the
      Stratus II analyzer.

PMID- 9166255
TI  - Designing in quality through design control: a manufacturer's perspective.
AB  - Quality by design is a comprehensive program that begins with understanding user
      needs and continues through (but does not end with) monitoring customer
      acceptance. Management tools and processes such as ISO 9000 standards and the
      Food and Drug Administration Quality System Regulations exist to guide medical
      device manufacturers in quality practices. The goal is to deliver products
      acceptable for their intended use. Quality control begins with defining
      attributes ranging from color to accuracy and precision. Failure mode and effects
      analysis and risk analysis consider both probability and severity of potential
      malfunctions and their effects on patients or operators. Tools used to implement
      design and production practices include Program Evaluation and Review Technique
      (PERT) charts and industry-conceived concepts, such as Six Sigma techniques.
      Their use varies with manufacturer, depending on product and customer needs and
      the manufacturer's specific quality practices. Verification confirms that input
      goals are met. Then, validation assures that intended clinical needs are
      continually satisfied by establishing adequate production specifications.
      Conformance is monitored to verify that stable, consistent processes are in
      place, and precise user instructions enable the device to satisfy its intended
      use. Finally, complaint tracking can help assess whether needs have been met.
      Modifications in service, hardware, or instructions (including quality control)
      might be required. Therefore, both manufacturers and users work in partnership
      for continual improvement. The manufacturer's knowledge of design, production,
      and service needs of its devices enable it to recommend appropriate quality
      control protocols for clinical testing.

PMID- 9166256
TI  - Defining the best quality-control systems by design and inspection.
AB  - Not all of the many approaches to quality control are equally effective.
      Nonconformities in laboratory testing are caused basically by excessive process
      variation and mistakes. Statistical quality control can effectively control
      process variation, but it cannot detect or prevent most mistakes. Because
      mistakes or blunders are frequently the dominant source of nonconformities, we
      conclude that statistical quality control by itself is not effective. I explore
      the 100% inspection methods essential for controlling mistakes. Unlike the
      inspection techniques that Deming described as ineffective, the new "source"
      inspection methods can detect mistakes and enable corrections before
      nonconformities are generated, achieving the highest degree of quality at a
      fraction of the cost of traditional methods. Key relationships between task
      complexity and nonconformity rates are also described, along with cultural
      changes that are essential for implementing the best quality-control practices.

PMID- 9166257
TI  - Panel discussion: how to monitor and minimize variation and mistakes.

PMID- 9166258
TI  - Thoughts on quality-control systems: a laboratorian's perspective.
AB  - State-of-the-art prospective quality-control systems entail the use of medically
      relevant, analyte-specific quality control limits. With analyte-specific limits
      broader than those generally used in the clinical laboratory, there will be fewer
      false rejections, fewer unnecessary reanalyses, and shorter delays in run
      reporting. If the analyte-specific limits are narrower than those used in the
      laboratory, more errors will be detected, but the user is at risk of identifying
      errors over which s/he and the manufacturer have little control. The use of
      various patient data quality-control algorithms is described. Conservatism is
      stressed in adopting manufacturers' guidelines for surrogate, nondestructive
      quality-control testing. A simple, optimized approach is suggested for the
      systematic retrospective review of proficiency data. Finally, an approach is
      presented for converting from older, previously accepted quality control
      procedures to more efficient analyte-specific quality control.

PMID- 9166259
TI  - Quality systems for unit-use testing devices.
AB  - Unit-use testing or single-test-system analysis has existed for many years.
      Quality-control and quality-assurance procedures have generally used conventional
      methods and lyophilized or aqueous control materials. Because these materials
      were readily available and generally accepted, they became part of the quality
      assurance program for many early unit-use test systems such as the DuPont aca.
      Over the years, these control products became standard and are now required as
      part of good laboratory practice. Technically speaking, however, conventional
      quality-control methods and materials cannot completely control the test system
      when used in a unit-use or single-test-system device. When conventional control
      material is run on a unit-use single-test system, only that testing unit is
      checked. One cannot test every unit with control material because by definition
      these are single-test systems: Once the control has been run, the patient's
      sample cannot be run. Conventional quality-assurance and quality-control methods
      do not, of themselves, assure quality. A one-size-fits-all, or "two levels per
      day of use" as outlined in the CLIA '88 regulations, is not appropriate. The
      divergence between HCFA-approved practices and those of the deemed agencies,
      coupled with the financial aspects of this quality-control method, led to the
      formation of the Subcommittee on Unit Use Testing of the National Committee on
      Clinical Laboratory Standards to develop guidelines for manufacturers, users, and
      regulators to use in developing new quality systems.

PMID- 9166260
TI  - How many mistakes, how to find them.
AB  - The topic of quality control often evokes prolific discussion among those whose
      business is its administration. Reliable methods for identifying mistakes must be
      developed in both the manufacture and use of test devices. Unit test devices are
      uncomplicated to run and provide quick results in a world where speed and
      simplicity are paramount, yet their very nature as individual assay units
      introduces questions about the relevance of conventional quality control
      procedures. Hybritech's ICON QSR CKMB assay is a unit test device that requires
      daily monitoring according to CLIA'88 regulations. The challenge is to ensure
      that quality-control testing is value-added, assuring clinicians valid patient
      sample results although controls are run in a separate "assay." We find that
      conventional quality-control procedures are indeed valid; however, the
      fundamental difference of unit test devices must be recognized and accounted for
      by understanding the capability of the assay in each laboratory.

PMID- 9166261
TI  - Quality: the next six months.
AB  - The eclectic mix of participants in the forum had a surprisingly singular focus
      when it came to the topic of quality in clinical laboratories. All sensed that
      the time is right for a transition from laws, rules, and inspections to a true
      quality-based system. Such a system can achieve the goals, implicit and explicit,
      that are the rationale for the multiplicity of regulations affecting today's
      laboratories. A true quality-based system has great potential benefits to
      laboratories, regulators, and manufacturers, and ultimately to our true
      customers, the patients. The benefits include lower costs, superior products, and
      better test results; in short, better patient care. This transition will be
      possible only through formation of a "Quality Alliance," composed of those
      skilled in the "theory" of quality-laboratory personnel, manufacturers, and
      regulators, acting as one to implement the quality system. The Quality Alliance
      requires a team of individuals with different skills, aligned as one, for the
      purpose of achieving a common goal. On the basis of views expressed in this
      Forum, our collective future will be defined by the evolving Quality Alliance, an
      alliance focused on true quality systems in clinical laboratories.

PMID- 9166262
TI  - Decision-making laboratory computer systems as essential tools for achievement of
      total quality.
AB  - Areas other than the analytical process should be the focus of concern about
      quality issues in the laboratory because nearly 95% of errors occur at the
      nonanalytical front and back ends of the testing process. Until now, computer
      systems have been designed to handle the more predictable aspects of laboratory
      testing, necessitating that the infrequent and unpredictable data events be
      handled by manual systems. The manual systems are termed "workarounds" and
      indeed, because they occur sporadically, they are frequently not handled
      predictably. Here, I describe and give examples of an expert laboratory computer
      system that can be designed to handle both predictable and unpredictable data
      events without the use of manual workarounds. This expert system works in concert
      with a dynamic database allowing such data events to be detected in real time and
      handled predictably, thus providing a tool to address quality assurance issues
      throughout the testing process. The system performs up to 31 separate actions or
      tasks based on data events that in the past were handled by human workarounds.

PMID- 9166263
TI  - Prospects for prevention of graft stenosis and angioplasty restenosis.

PMID- 9166264
TI  - Ruptured popliteal artery aneurysm. An insidious complication.
AB  - OBJECTIVES: To evaluate the incidence and clinical presentation of ruptured
      popliteal aneurysms. METHODS: The records of 89 consecutive patients, all males,
      seen between 1958 and 1995 with 124 arteriosclerotic popliteal aneurysms were
      reviewed retrospectively. Most aneurysms were symptomatic (69/124; 55.6%). In six
      cases (6/124; 4.8%) a rupture was present. RESULTS: There was a wide range in
      primary diagnosis varying from deep venous thrombosis to peroneal nerve palsy. In
      all cases primary reconstructive surgery was performed. No primary or secondary
      amputations were necessary. Surgical outcome was good in four cases. In the
      remaining cases one patient suffered from a permanent peroneal nerve palsy and
      one from non-disabling claudication. Review of the literature showed a rupture
      incidence of 2.5% (range 0-16%) and amputation rates as high as 100%. CONCLUSION:
      An acute rupture of a popliteal aneurysm is rare. Although the clinical
      presentation can be non-specific, this possibility must be especially taken into
      account when dealing with older male patients presenting with signs and symptoms
      of generalised atherosclerosis and non-specific pain in the popliteal region.

PMID- 9166265
TI  - Residual arteriovenous fistulae after "closed" in situ bypass grafting: an
      overrated problem.
AB  - OBJECTIVES: To prospectively evaluate the incidence and consequences of residual
      arteriovenous (AV)-fistulae after "closed" in situ bypass grafting. METHODS: In
      34 patients, 35 "closed" in situ bypasses were performed. Postoperative
      assessment of residual AV-fistulae and bypass patency was performed with duplex
      scanning. RESULTS: Postoperative mortality was 3%. During 35 "closed" in situ
      bypass procedures 216 side branches were coil embolised. Postoperatively 39 AV
      fistulae were detected (15% of the total number of 216 + 39 = 255 side branches).
      Of these, 13 (5%) closed spontaneously. Fifteen (6%) remained unchanged and 11
      (4%) were treated. In three patients four asymptomatic residual AV-fistulae were
      treated. In four patients seven symptomatic AV-fistulae were treated for:
      decreased distal bypass flow in one; persistent leg oedema in one; pain and
      redness of the skin in two. One-year primary patency was 80% (SE 8.4%). Residual
      AV-fistulae were detected in none of six bypass occlusions during follow-up.
      CONCLUSION: Residual AV-fistulae detected following "closed" in situ bypass
      grafting only need treatment if they are symptomatic, which is uncommon.

PMID- 9166266
TI  - Wall shear stress and early atherosclerotic lesions in the abdominal aorta in
      young adults.
AB  - OBJECTIVES: To study the correlation between wall shear stress and early
      atherosclerotic lesions in the abdominal aorta. DESIGN: Blinded histomorphometric
      studies. Comparison with in vitro data. MATERIALS: Abdominal aortic haemodynamics
      were simulated in a realistic pulsatile flow model. Abdominal aortas from 10
      young adults with no signs of atherosclerotic disease were obtained during
      autopsy. METHODS: Quantitative wall shear stresses were measured at rest and
      exercise in one suprarenal and two infrarenal positions using laser Doppler
      anemometry. Intimal thickening indices were measured blindly at the corresponding
      locations using histomorphometric methods, and compared to wall shear stress
      variables using linear regression analysis. RESULTS: Intimal thickness index
      increased significantly with age. Intimal thickness index was significantly lower
      in the suprarenal than the infrarenal aorta, and higher at the distal posterior
      vessel wall compared to the anterior wall. Intimal thickness index correlated
      significantly with mean, minimum and oscillating wall shear stresses measured at
      rest. CONCLUSION: Intimal thickness in the undiseased abdominal aorta correlated
      significantly with mean, minimum and oscillating wall shear stresses at rest
      measured in a pulsatile flow model. No correlations were found with maximum shear
      stress parameters. Exercise changed the local wall shear stresses away from the
      characteristics associated with intimal thickness index.

PMID- 9166267
TI  - Surgical treatment for chronic critical leg ischaemia: a 5 year follow-up of
      socioeconomic outcome.
AB  - OBJECTIVES: To evaluate the costs of amputation and arterial reconstruction for
      chronic critical leg ischaemia (CLI). DESIGN: A 5 year follow-up study of
      patients with primary intervention for CLI. SETTING: One regional and two
      district hospitals serving a defined population. MATERIAL: One hundred and
      seventeen consecutive patients undergoing reconstructive arterial surgery or
      amputation for CLI. CHIEF OUTCOME MEASURES: Additional procedures, treatment
      resources and costs related to the treatment of CLI. MAIN RESULTS: Reconstruction
      patients needed frequent reinterventions due to graft problems, additional CLI
      symptoms and revisions of ischaemic tissue. The mean costs for a reconstruction
      were 240,000 FIM/patient and 70,000 FIM/survival year including costs for later
      amputations. Patients with a reconstruction without later amputation had costs of
      175,000/ patient and 47,000/survival year. A reconstruction with a later
      amputation had the highest costs, 402,000/patient and 148,000/survival year.
      Contralateral leg ischaemia caused a new intervention in 25% of all patients. For
      non-institutionalised patients an amputation resulted in institutional treatment
      in over 20% of the remaining surviving days with a cost of 313,000 FIM/patient
      and 150,000 FIM/survival year. CLI in institutionalised patients with a primary
      amputation had a short stay in hospital, needed little additional resources and
      caused only low additional costs. CONCLUSIONS: Costs for a reconstruction in
      potentially mobile, independently living patients with CLI is similar to those of
      an amputation. It often demands repeated interventions to achieve good results.
      On a cost/survival year basis, amputations carry higher costs. For
      institutionalised, immobile patients with CLI an amputation is often the only
      possible and cheapest treatment.

PMID- 9166268
TI  - Comparison of cost affecting parameters and costs of the "closed" and "open" in
      situ bypass technique.
AB  - OBJECTIVES: The "closed" in situ bypass results in a reduction of wound
      complications compared to the "open" technique. This advantage is partly
      diminished by extra costs for the "closed" procedure and a larger percentage of
      residual arteriovenous (AV)-fistulae. This aim of this study was to analyse costs
      related to "closed" and "open" procedures. METHODS: The cost affecting
      parameters: (1) duration of operation; (2) length of hospital stay; and (3)
      number of treated residual AV-fistulae, were analysed in a randomised group of 73
      patients (35 "closed" and 38 "open") in two centres. In addition, costs of the
      operation, nursing care and treatment of AV-fistulae were analysed. RESULTS: The
      "closed" and "open" group showed a median duration of operation of 210 min (range
      105-570) and 154 min (range 90-355) (p < 0.05), length of hospital stay of 16
      days (range 5-51) and 25 days (range 12-65) (p < 0.01), and a percentage of
      patients treated for residual AV-fistulae of 40% and 5%, respectively (p < 0.01).
      The median "closed" operation was US$798 more expensive than the "open". Median
      postoperative care was US$2664 less for the "closed" group. Mean estimated costs
      for treatment of AV-fistulae was US$9 in the "open" and US$167 in the "closed"
      group. CONCLUSION: The "closed" in situ vein bypass technique is cost-effective
      in comparison with the "open" technique.

PMID- 9166269
TI  - Discriminative microcirculatory screening of patients with refractory limb
      ischaemia for dorsal column stimulation.
AB  - OBJECTIVES: (1) To determine the proportion of patients with critical limb
      ischaemia refractory to invasive treatment that can be successfully treated by
      dorsal column stimulation (DCS), and (2) to identify potential responders to DCS
      by a simple test that is sufficiently predictive to limit the need for a
      prolonged trial stimulation period. PATIENTS AND METHODS: Twenty patients with
      chronic limb-threatening ischaemia were assessed by a battery of macro- and
      microcirculatory tests and a DCS trial of 1 week. Favourable response during the
      trial determined selection for long-term stimulation. RESULTS: During a mean
      observation period of 14 months, limb salvage rate (LSR) was 63% overall and 83%
      among patients selected after a favourable trial. Of the tests performed
      preoperatively, digital subtraction angiography, Doppler assessment,
      oscillometry, capillaroscopy, foot temperature, and transcutaneous partial
      pressure of oxygen (tcpO2) in the supine or sitting position did not adequately
      predict DCS response. The supine-sitting tcpO2 gradient (delta tcpO2) was a good
      predictor of DCS outcome, with an 88% LSR when delta tcpO2 > 15 Torr, dropping to
      12% when delta tcpO2 < or = 15 Torr. CONCLUSIONS: DCS is a rewarding therapeutic
      option in selected patients with critical limb ischaemia. delta tcpO2 appears to
      reliably predict response to DCS and may obviate trial stimulation in most cases.

PMID- 9166270
TI  - Concurrent comparison of endoluminal repair vs. no treatment for small abdominal
      aortic aneurysms.
AB  - Endoluminal repair of abdominal aortic aneurysms (AAA) requires the aneurysm to
      have a proximal neck of at least 1.5 cm between the renal arteries and the
      aneurysm. Therefore, there may be advantages in performing endoluminal repair in
      the early stages of aneurysm development. However, the results of endoluminal
      repair performed in patients with small aneurysms with favourable morphology are
      not known. The aim of this study was to determine whether a randomised trial of
      endoluminal repair vs. no treatment for small aneurysms would be justified by
      using a concurrent comparison of endoluminal repair vs. no treatment for AAA 5 cm
      or less in diameter in patients presenting to the same centre during a 4-year
      period. METHODS: Data on 117 patients presenting with AAA 5 cm or less in
      diameter were entered into a registry. The decision to perform endoluminal repair
      vs. no treatment was based on the patient's preference following surgical
      consultation and investigation by computed tomography. This study reports the
      mortality, morbidity and survival of patients presenting between June 1992 and
      August 1996. During this time 43 patients had endoluminal repair and 67 patients
      had no treatment for small AAA. Seven patients were unfit for any intervention.
      Despite patient selection for different management in each group, close analysis
      revealed that the groups were similar with regard to co-morbidities and risk
      factors, as well as age, sex, and size of aneurysm. Follow-up was by progress CT
      scanning and ranged from 1 to 51 months (mean 18 months (NT) and 22 months (ER)).
      RESULTS: Endoluminal repair failed in six of 43 patients (14%) and resulted in 11
      (25%) local vascular complications. There were two perioperative deaths and one
      late death in this group. Twenty-one of 67 AAA (31%) patients in the no treatment
      group enlarged beyond 5 cm in diameter during the study period. There was one
      death from aneurysm rupture and one death from myocardial infarction in this
      group. CONCLUSIONS: The patients in the endoluminal repair group have gained an
      asset in having their aneurysms repaired at a cost of early morbidity following
      operation. These results suggest that a randomised trial of endoluminal repair
      vs. no treatment will become justified in the subset of patients with small AAA 5
      cm or less, if the incidence of complications can be reduced by further
      improvements in endoluminal technology.

PMID- 9166271
TI  - The concept of knee salvage: why does a failed femorocrural/pedal arterial bypass
      not affect the amputation level?
AB  - OBJECTIVES: There is continued controversy over whether a failed distal bypass
      influences the level of amputation. This issue is important as the number of
      arterial bypass grafts undertaken for critical ischaemia is increasing, followed
      by an increasing number of failed grafts. SETTING: Teaching hospital. STUDY
      DESIGN AND MATERIALS: A prospective analysis of 109 consecutive
      femorocrural/pedal bypass grafts performed between June 1991 and January 1995 on
      patients presenting with severe critical lower limb ischaemia (CLI) to a single
      vascular unit. A further 43 amputations for non-reconstructible distal disease
      were also analysed. CHIEF OUTCOME MEASURES: Mortality, amputation,
      rehabilitation, survival and knee salvage rates. The Kaplan-Meier method was used
      for comparison of factors associated with knee preservation. RESULTS: Primary
      amputees had a higher in-hospital mortality (18% vs. 10%) but similar 3 year
      survival rates (30%) compared with secondary amputees (36.6%). Patients with
      successful grafts showed a trend towards better survival (61.9% at 3 years)
      compared to amputees (38.6% at 42 months, p = 0.061). Below- to above-knee
      amputation ratio was similar in the two groups (0.85 in secondary vs. 0.95 in
      primary amputees). Factors significantly associated with knee salvage at 3 years
      were shown to be: the condition of the inflow (81.9% for good vs. 43.1% for
      impaired, p = 0.000) the state of the profunda femoris artery (good 93%, impaired
      71%, occluded 37% p = 0.0001) and the graft material (vein 81.8% vs. PTFE 59.8%,
      p = 0.033). The presence of tissue loss (p = 0.0523) and secondary procedures (p
      = 0.0879) showed a trend to become significant. Multivariate and Cox regression
      analysis showed that the most important factors were the inflow (p = 0.001), the
      state of the profunda (p = 0.001), the graft material (p = 0.034) and previous
      revascularisation attempts (p = 0.019). CONCLUSIONS: The factors which determine
      knee loss are a compromised inflow state, the presence of an inadequate profunda
      femoris, previous revascularisation attempts and the use of synthetic graft
      material. Most of these factors (with the exception of infection related to
      revascularisation) are present before reconstructive arterial surgery is
      performed and this study shows that failure of a distal graft does not affect the
      final amputation level.

PMID- 9166272
TI  - Effect of walking distance on the change in ankle-brachial pressure index in
      patients with intermittent claudication.
AB  - OBJECTIVES: The ankle-brachial pressure index (ABPI) responses to different
      exercise intensities on a treadmill were evaluated to clarify the relationship
      between intermittent claudication and the haemodynamics in the leg. PATIENTS AND
      METHODS: Thirty patients with intermittent claudication (32 symptomatic legs) due
      to peripheral arterial occlusive disease were exercised on a treadmill to
      determine their pain-free walking distance, maximum walking distance (MWD) and
      recovery time. Each subject was exercised at 25% and 50% of the MWD to determine
      the effect of work intensity on the drop in ABPI, and the recovery time. RESULTS:
      In the claudicating legs, 25% of the MWD resulted in almost the same reduction in
      ABPI as 50% of the MWD, and the MWD. In contrast, the ABPI in the asymptomatic
      legs (13) was significantly decreased in proportion to the walking distance. The
      recovery time increased linearly in both the groups, as the walking distance
      increased. CONCLUSION: The recovery time of the ABPI correlated well with the
      intensity of workload, while the drop in ABPI did not.

PMID- 9166273
TI  - Local versus general anaesthesia in carotid endarterectomy: a systematic review
      of the evidence.
AB  - OBJECTIVE: To determine whether carotid endarterectomy under local anaesthesia is
      safer and as effective as under general anaesthesia. DESIGN: Systematic review of
      the randomised and non-randomised studies. MATERIALS: Studies were identified
      from the Cochrane Stroke Group's database plus additional handsearching and
      electronic searching. METHODS: Two authors independently selected studies for
      inclusion and extracted details of trial quality and data on death, any stroke,
      myocardial infarction and other operative complications. Meta-analysis was
      performed using the Peto method. RESULTS: There were 17 non-randomised studies
      (about 5970 patients) and only three randomised studies (143 patients). The non
      randomised studies suggested that the use of local anaesthesia may be associated
      with clinically important reductions (approximately 50%) in the odds of stroke,
      stroke or death, myocardial infarction and pulmonary complications during the
      perioperative period, and with reductions in hospital stay. There were far too
      little data from the randomised trials to confirm or refute these findings: only
      one death and seven strokes were reported. CONCLUSIONS: Non-randomised studies
      suggest potentially important benefits from performing carotid endarterectomy
      under local anaesthesia. However, these studies were seriously flawed and can
      only be hypothesis generating. The results must be confirmed in large well
      designed randomised trials before any recommendations on the use of local
      anaesthetic can be made.

PMID- 9166274
TI  - Long-term prognosis for patients with chronic leg ulcers: a prospective cohort
      study.
AB  - OBJECTIVES: To assess the long-term prognosis of leg ulcers. DESIGN: A 5 year
      prospective cohort study. MATERIALS: A random sample of 382 patients with open
      leg ulcers (foot ulcers included) treated in the community. METHODS: Interim
      analyses were made at 15 months (arterial ulcers) and at 20 months (varicose
      ulcers). Long-term healing was assessed at 54 months by a postal questionnaire.
      Five year survival was assessed by official population registries. RESULTS: At 54
      months 212 patients (55%) were still alive, of whom 124 (58%) had healed their
      ulcers, 80 (38%) had open ulcers and eight (4%) were amputated. The healing was
      worst for patients with venous ulcers, only 44% had healed their original ulcers
      without recurrence. The 5 year survival was 52%, significantly lower than for age
      and sex-matched controls (68%) (p = 0.0002). Patients with venous ulcers had a
      survival not significantly different from controls and patients with arterial or
      other aetiologies had a doubled risk of death. Diabetic patients had a lower
      survival than non-diabetics (p < 0.05) and controls (p < 0.0001), but the healing
      prognosis was not significantly different. CONCLUSION: Only patients with non
      venous ulcers have a higher mortality than expected. The long-term healing
      prognosis for leg ulcer patients is poor and worst for patients with venous
      ulcers.

PMID- 9166275
TI  - Spontaneous rupture of the renal artery in a patient with Ehlers-Danlos syndrome
      type IV.

PMID- 9166277
TI  - Successful use of recombinant tissue plasminogen activator in the treatment of
      aortic thrombosis in a premature neonate.

PMID- 9166276
TI  - Successful non-surgical management of traumatic pseudoaneurysm of the axillary
      artery by duplex guided compression obliteration.

PMID- 9166278
TI  - Aortic dissection due to Clostridium septicum infection.

PMID- 9166279
TI  - Insulin-like growth factors prevent apoptosis in cortical neurons isolated from
      stroke-prone spontaneously hypertensive rats.
AB  - Cerebral ischemia induces a massive efflux of glutamate causing delayed neuronal
      death in stroke-prone spontaneously hypertensive rats (SHRSP) but not in Wistar
      Kyoto rats (WKY). It is obvious that L-N-nitroarginine (L-NNA; NO synthase (NOS)
      inhibitor), benzamide (poly(ADP-ribose) synthetase inhibitor), and growth factors
      are involved in reducing neuronal cell death due to toxic conditions, especially
      phosphatidylinositol 3 (PI3)-kinase activity; however, no studies have clarified
      whether genetic vulnerability to neurotoxic states is present in cortical neurons
      isolated from SHRSP. For this purpose, we prepared cortical neurons from WKY and
      SHRSP (15 weeks of gestation) to test the genetic vulnerability involved in the
      pathogenesis of stroke as well as apoptosis of cortical neurons isolated from
      SHRSP. We also examined the mechanisms necessary to reduce apoptosis under
      neurotoxic states using ultrastructural and biochemical techniques. Cortical
      neurons from SHRSP were in fact found to be more vulnerable than neurons from WKY
      and resulted in apoptosis when treated with nitric oxide (NO)- and N-methyl-D
      aspartate (NMDA)-mediated neurotoxic agents. Growth factors, especially insulin
      like growth factor (IGF), rescued neurons from NO- and NMDA-mediated
      neurotoxicity, particularly those from SHRSP. Conversely, benzamide and L-NNA
      reduced NMDA-mediated neurotoxicity but not NO-mediated toxicity. The ability to
      protect neurons from neurotoxicity was as follows: IGF-->nerve growth factor
      epidermal growth factor-->L-NNA-->benzamide. In addition, it was demonstrated
      that wortmannin, a PI3-kinase inhibitor, lessened the protective effects of these
      growth factors against NO-mediated toxicity. The data thus indicate that genetic
      factors related to neuronal vulnerability to apoptosis are involved in the
      pathogenesis of stroke lesions in SHRSP. PI3-kinase activity, which is stimulated
      by growth factors, is closely related to protective effects against NO- and NMDA
      mediated toxicity in cortical neurons, especially those isolated from SHRSP.
      Moreover, the genetic vulnerability observed in SHRSP neurons is possibly linked
      to the inadequate activation of signaling pathways in the downstream of protein
      tyrosine kinases.

PMID- 9166280
TI  - Insulin-like growth factor-1 attenuates apoptosis in hippocampal neurons caused
      by cerebral ischemia and reperfusion in stroke-prone spontaneously hypertensive
      rats.
AB  - Cerebral ischemia followed by reperfusion induced apoptosis in stroke-prone
      spontaneously hypertensive rats (SHRSP) but not in Wistar Kyoto rats (WKY). Our
      in vitro studies revealed that IGF-1 prevented apoptosis caused by nitric oxide-
      and N-methyl-D-aspartate-mediated toxic agents in cortical neurons isolated from
      SHRSP. In addition, it was reported that IGF-1 given 1 hour before ischemia
      significantly attenuated the incidence of myocyte apoptosis after myocardial
      ischemia and reperfusion. IGF-1 (20 micrograms/rat) was administered ip 1 hour
      before the clipping of both common carotid arteries in WKY and SHRSP. Rats
      underwent cerebral ischemia for 20 minutes and reperfusion for 6 days before they
      were killed. We cut the brain coronally, removed sections from the hippocampal
      CA1 region, and examined the neurons in these samples using an electron
      microscope. We tried to clarify whether pretreatment using IGF-1 decreases the
      number of apoptotic neurons in SHRSP with cerebral ischemia followed by
      reperfusion. SHRSP with normal cerebral circulation had 30.4 +/- 8.0 apoptotic
      neurons per 1000 neurons. Cerebral ischemia followed by reperfusion significantly
      (p < 0.01) increased the number of apoptotic neurons (235.2 +/- 25.2/1000
      neurons) in SHRSP. In contrast, pretreatment with IGF-1 reduced the number of
      apoptotic neurons in SHRSP (82.8 +/- 11.2/1000 neurons; p < 0.01) under otherwise
      identical conditions. We concluded that the genetic vulnerability to apoptosis in
      SHRSP neurons was involved in the pathogenesis of stroke lesions and that this
      vulnerability was attenuated by the IGF-1 pretreatment.

PMID- 9166281
TI  - Interleukin-10 is a mesangial cell growth factor in vitro and in vivo.
AB  - Macrophages are involved in the pathogenesis of mesangioproliferative
      glomerulonephritis. As macrophages are known to produce interleukin-10 (IL-10),
      we investigated the effect of recombinant murine IL-10 (rIL-10) on mesangial cell
      growth. In vitro studies were performed using the rat 1097 mesangial cell line.
      These cells exhibited a dose-dependent proliferative response to rIL-10 (23% to
      70% increases at 80 ng/mL; p < 0.01), as assessed by both 3H-thymidine uptake and
      cell count. This effect was inhibited by preincubation of rIL-10 with a
      neutralizing anti-IL-10 antibody. When added to cultures of growth-arrested 1097
      cells, IL-10 induced dose-dependent proliferation that paralleled the effects of
      platelet-derived growth factor. Incubation with a neutralizing anti-IL-10 Ab for
      48 hours reduced 3H-thymidine uptake (median, 27% decreases; range, 2% to 56%
      decreases) versus a control Ab; p < 0.05). Rat mesangial cells were also shown to
      express IL-10 mRNA and protein, as determined by Northern blotting and
      immunostaining, thereby suggesting a role for IL-10 in autocrine mesangial cell
      growth. To examine the effects of IL-10 in vivo, inbred male Sprague-Dawley rats
      were given subcutaneous rIL-10 (0.5 mg/kg) for 3 (n = 6), 7 (n = 3), or 14 days
      (n = 4), or vehicle control, then killed. IL-10 administration induced a
      transient reduction in creatinine clearance of 35% at Day 3 (p < 0.01). Following
      IL-10 administration, an increase in glomerular cellularity was seen, which was
      maximal at Day 3 (82.7 +/- 5.9 nuclei/glomerular cross section versus control
      64.6 +/- 4.6, 28% increases; p < 0.001) and maintained at Day 14 (23% increases;
      p < 0.01). Immuno-histochemical staining for proliferating cell nuclear antigen
      demonstrated an increased number of proliferating cells per glomerular cross
      section at day 3 (48% increases versus controls; p < 0.05). Staining for alpha
      smooth-muscle actin showed significant labeling only in the glomeruli of IL-10
      treated animals; double-labeling with an anti-proliferating cell nuclear antigen
      Ab demonstrated that some of these mesangial cells were proliferating.
      Collectively, these results suggest that IL-10 is a growth factor for rat
      mesangial cells both in vitro and in vivo.

PMID- 9166282
TI  - Analysis of the inflammatory cytokine network among TNF alpha, IL-1 beta, IL-1
      receptor antagonist, and IL-8 in LPS-induced rabbit arthritis.
AB  - We investigated the cytokine network in rabbit lipopolysaccharide (LPS)-induced
      arthritis, using inhibitors against homologous TNF alpha, IL-1 beta, and IL-8.
      Rabbits were intraarticularly injected with LPS (10 ng) and cytokine inhibitors
      (10 micrograms each), and the concentrations of each cytokine in the synovial
      fluids were measured. Maximum levels of TNF alpha and IL-8 were detected at 2
      hours after LPS-injection, whereas IL-1 beta and IL-1 receptor antagonist (IL
      1Ra) were detected at 6 and 9 hours, respectively. By immunohistochemistry,
      synovial lining cells were positive for TNF alpha and IL-8, and infiltrating
      leukocytes were positive for IL-1 beta and IL-1 Ra. The effects of cytokine
      inhibitors on the release of each cytokine were then investigated. The maximum
      levels of TNF alpha and IL-8 were not affected by blocking the activities of
      other cytokines. In contrast, the peak concentration of IL-1 beta was reduced by
      anti-TNF alpha monoclonal Ab (mAb), IL-1 Ra or anti-IL-8 IgG. Peak concentrations
      of IL-1Ra were reduced by anti-TNF alpha mAb or anti-IL-8 IgG. Anti-TNF alpha
      mAb, IL-1Ra, and anti-IL-8 IgG reduced the recruitment of leukocytes into the
      joint cavity, and the effect of anti-IL-8 IgG was less than that of anti-TNF
      alpha mAb plus IL-1Ra. The initial phase of the leukocyte influx was not
      inhibited. These results provide new evidence that IL-8 as well as TNF alpha are
      the most proximal cytokines and induce subsequent production of IL-1 beta and IL
      1Ra. The data also raise the possibility that factor(s) other than IL-8 may be
      involved in the leukocyte influx in LPS-induced arthritis.

PMID- 9166283
TI  - Cytotoxicity and apoptosis in human renal allografts: identification,
      distribution, and quantitation of cells with a cytotoxic granule protein GMP-17
      (TIA-1) and cells with fragmented nuclear DNA.
AB  - In the present study, we analyzed human renal allografts using
      immunohistochemical techniques to determine the site, identity, and frequency of
      (a) cytotoxic and apoptotic cells, as identified by staining for GMP-17 (TIA-1),
      a component of cytotoxic granules; and (b) DNA fragmentation in situ, as detected
      by the TUNEL method. In acute cellular rejection (n = 15), GMP-17+ mononuclear
      cells accounted for 29% +/- 12% of the infiltrating cells in the interstitium
      (341 +/- 164/mm2) and were significantly more concentrated in tubulitis lesions,
      where they amounted to 65% +/- 14% of the mononuclear cells (96 +/- 61/mm2) (p <
      0.01 versus interstitium). GMP-17+ mononuclear cells were also found in sites of
      endothelialitis. An estimated 80% of the GMP-17+ lymphocytes expressed CD8, and
      10% to 20% expressed either CD4 or the macrophage marker CD14. The latter finding
      led us to analyze normal peripheral blood monocytes by flow cytometry, all of
      which were found to contain GMP-17. NK cells and neutrophils, which are known to
      express GMP-17, were detected only rarely in allografts. Specimens with
      cyclosporine A toxicity (n = 7) or acute tubular necrosis (n = 13) showed fewer
      GMP-17+ cells in the interstitium (22 +/- 46/mm2 and 62 +/- 50/mm2, respectively)
      and tubules (2 +/- 6/mm2 and 10 +/- 10/mm2, respectively) (all p < 0.01 versus
      rejection). These differences were due largely to less intense mononuclear cell
      infiltration. In cyclosporine A toxicity, however, the percentages of GMP-17+
      mononuclear cells within tubules and the interstitium were significantly lower
      than in rejection (p = 0.02), whereas in acute tubular necrosis significantly
      lower percentages were found in the tubules (p = 0.04) but not in the
      interstitium. Native kidneys with end-stage diabetic nephropathy (n = 5) had very
      low proportions of GMP-17+ cells in interstitial infiltrates (7% +/- 6%) and in
      tubules (11% +/- 15%), although the infiltrates were focally intense (517 +/-
      355/mm2). TUNEL+ cells were found in acute cellular rejection, predominantly in
      areas with intense mononuclear infiltrates and also within lesions of tubulitis
      and endothelialitis. Although some TUNEL+ cells were intrinsic renal cells, most
      appeared to be infiltrating mononuclear cells, and we were able to detect CD3 in
      some. In areas of intense cellular infiltration, the percentages of TUNEL+ cells
      (range, 0.5% to 4.2%) were comparable to those seen in the rat thymus, indicating
      a high level of apoptosis. Overall, in the allograft samples, the numbers of GMP
      17+ cells and TUNEL+ cells were significantly correlated (r = 0.79; p < 0.01).
      These data provide new evidence that T cell (and possibly macrophage)-mediated
      cytotoxicity plays an important role in acute renal allograft rejection,
      particularly in the case of tubular injury, and furthermore suggest that
      apoptosis may be a mechanism not only for graft cell destruction, but also for
      elimination of activated T cells in the infiltrate.

PMID- 9166284
TI  - Implication of collagen type I-induced membrane-type 1-matrix metalloproteinase
      expression and matrix metalloproteinase-2 activation in the metastatic
      progression of breast carcinoma.
AB  - We have previously demonstrated that fibroblasts and invasive human breast
      carcinoma (HBC) cells specifically activate matrix metalloproteinase-2 (MMP-2)
      when cultured on 3-dimensional gels of type I collagen but not a range of other
      substrates. We show here the constitutive expression of membrane-type 1 (MT1)-MMP
      in both fibroblasts, and invasive HBC cell lines, that have fibroblastic
      attributes presumably acquired through an epithelial-to-mesenchymal transition
      (EMT). Treatment with collagen type I increased the steady-state MT1-MMP mRNA
      levels in these cells but did not induce either MT1-MMP expression or MMP-2
      activation in noninvasive breast carcinoma cell lines, which retain epithelial
      features. Basal MT3-MMP mRNA expression had a pattern similar to that of MT1-MMP
      but was not up-regulated by collagen. MT4-MMP mRNA was seen in both invasive and
      noninvasive HBC cell lines and was also not collagen-regulated, and MT2-MMP mRNA
      was not detected in any of the HBC cell lines tested. These data support a role
      for MT1-MMP in the collagen-induced MMP-2-activation seen in these cells. In situ
      hybridization analysis of archival breast cancer specimens revealed a close
      parallel in expression of both collagen type I and MT1-MMP mRNA in peritumoral
      fibroblasts, which was correlated with aggressiveness of the lesion. Relatively
      high levels of expression of both mRNA species were seen in fibroblasts close to
      invasive tumor nests and, although only focally, in certain areas close to
      preinvasive tumors. These foci may represent hot spots for local degradation and
      invasive progression. Collectively, these results implicate MT1-MMP in collagen
      stimulated MMP-2 activation and suggest that this mechanism may be employed in
      vivo by both tumor-associated fibroblasts and EMT-derived carcinoma cells to
      facilitate increased invasion and/or metastasis.

PMID- 9166285
TI  - Interphase cytogenetic analysis of mucinous ovarian neoplasms.
AB  - Extending our previous efforts to characterize ovarian neoplasms by interphase
      cytogenetics, we analyzed a series of 32 mucinous tumors by nonisotopic in situ
      hybridization with seven different centromere-specific probes as well as by flow
      and image DNA cytometry; we then compared the data with results of p53 and Ki67
      immunohistochemistry and MYC DNA-PCR analysis and of the clinical follow-ups. Of
      the tumors studied, 11 of 14 (78.6%) mucinous carcinomas, 7 of 7 (100%) mucinous
      tumors of low malignant potential (LMP), and 7 of 11 (63.6%) mucinous
      cystadenomas demonstrated chromosomal aberrations. The mean number of chromosomal
      aberrations (+/- SD) was slightly higher in DNA cytometrically nondiploid cases
      than in diploid cases (2.0 +/- 1.6 versus 1.6 +/- 1.2, not significant) but did
      not differ significantly among the study groups (carcinomas: 1.7 +/- 1.4; tumors
      of LMP; 1.9 +/- 0.7; adenomas: 1.4 +/- 1.4). Aberrations affected chromosomes 1
      (14 of 27 cases) and 6 (12 of 31) most frequently, followed by chromosomes 17 (7
      of 28), 7 (6 of 29), and X (6 of 28). Signal gain for centromere 1, which was the
      most prevalent finding (13 of 27), was observed in 3 of 10 mucinous cystadenomas,
      2 of 4 mucinous tumors of LMP, and 8 of 13 mucinous carcinomas. All six
      moderately and poorly differentiated carcinomas demonstrated this aberration.
      Signal gain of centromere 6 (3 of 13) and centromere 7 (4 of 13) were found only
      in carcinomas (p < 0.05 and p < 0.025, respectively). The interphase cytogenetic
      results correlated neither with proliferative activity, immunohistochemical p53
      accumulation, MYC DNA amplification, nor postoperative outcome. Compared with
      serous ovarian neoplasms (Lab Invest 1996, 75:473-485), mucinous tumors
      demonstrated signal gain for chromosome 1 (p < 0.0001) and signal loss for
      chromosomes 6 (p < 0.001) and X (p < 0.01) significantly more often. Loss of
      centromere 17 was more characteristic for serous than for mucinous carcinomas (p
      < 0.05). Our observations show that chromosomal aberrations in mucinous ovarian
      neoplasms are apparently not random. These results support the notion that the
      molecular genetic changes in mucinous neoplasms differ from those in serous
      tumors.

PMID- 9166286
TI  - Influence of glucose on murine metanephric development and proteoglycans:
      morphologic and biochemical studies.
AB  - The offspring of severe juvenile diabetics suffer from a multitude of congenital
      anomalies, including genito-urinary defects. Whether these defects are related to
      hyperglycemic states remains to be determined. In this study, the effect of
      glucose on metanephric development and extracellular matrix proteoglycans (PG),
      the regulators of morphogenesis, was investigated. Metanephric explants,
      harvested at Day 13 of gestation, were exposed to 30 mM of D-glucose for 1 to 7
      days in an organ culture system. Light microscopy revealed a significant
      reduction in the size of explants and the nephron population in metanephroi
      exposed to glucose. A marked dysmorphogenesis of the ureteric bud branches was
      also observed. They were swollen and had blunted tips. The latter are the site of
      nascent nephron formation. Electron microscopy revealed malformation of the S
      shaped body nephrons, which had poorly formed clefts and lacked cells in their
      distal convolutions. The precapillary stage glomeruli showed effacement of the
      foot processes, attenuation of the glomerular basement membrane, decreased
      surface microvilli, and an increased number of intercellular junctions.
      Immunofluorescence microscopy indicated a decreased reactivity of antibody
      directed against basement membrane heparan sulfate-PG. By light microscopy
      autoradiography, a generalized decrease in [35S] sulfate incorporation was
      observed, especially at the tips of the ureteric bud branches. Electron
      microscopy-autoradiography revealed a significant decrease in the silver grain
      density (concentration of radiation) in the matrix compartment of the nephrons,
      i.e., cleft of the S-shaped body and glomerular basement membrane of the
      precapillary-stage glomeruli. Biochemical studies revealed a decrease in the
      incorporated radioactivity associated with the fraction of PG. The newly
      synthesized PG had a reduction in their molecular weight and charge-density
      characteristics but had an increased proportion of chondroitin sulfate. These
      data suggest that D-glucose induces marked dysmorphogenesis of the embryonic
      kidney during in vitro metanephric development and that these alterations may be
      related to perturbations in the de novo synthesis of PG, one of the essential
      morphogenetic regulators of the extracellular matrix.

PMID- 9166287
TI  - Multiple forms of messenger ribonucleic acid encoding glycodelin in male genital
      tract.
AB  - Glycodelin-A is a human endometrium-derived glycoprotein with contraceptive and
      immunosuppressive activities. Recently, we found that seminal plasma contains
      immunoreactive glycodelin (GdS) that is differentially glycosylated and has no
      contraceptive activity. We now report localization and variant forms of GdS in
      the male genital tract. Northern blot and reverse transcription-PCR analyses
      showed that GdS mRNA is expressed in the seminal vesicles and ampulla of the vas
      deferens. Immunohistochemical staining localized GdS to the epithelial cells and
      lumen of glands in the seminal vesicles and ampullary part of the vas deferens.
      The same tissues and cells contained glycodelin mRNA as localized by in situ
      hybridization. Whereas the major reverse transcription-PCR products were
      identical to the glycodelin-A cDNA from decidual expression library, there were
      also several splicing variants of GdS mRNA. Seminal plasma also contained smaller
      immunoreactive forms of the GdS protein. Some of them were posttranslational
      cleavage products of GdS, because incubation of 125I-labeled GdS in seminal
      plasma resulted in smaller molecular weight cleavage products. Based on these
      results, we concluded that multiple forms of glycodelin mRNA are expressed in the
      male genital tract, including those lacking the coding sequences for the
      glycosylation sites, and that seminal plasma has proteolytic activity that
      cleaves GdS.

PMID- 9166288
TI  - Coxsackievirus-induced myocarditis is dependent on distinct immunopathogenic
      responses in different strains of mice.
AB  - Myocarditis is defined as an inflammation of the heart muscle and often follows
      enterovirus infections. Frequently, patients surviving the acute inflammatory
      stage undergo complete recovery, but myocarditis can result in dilated
      cardiomyopathy. A murine model of myocarditis has been developed that uses
      cardiotropic variants of coxsackievirus Group B. Type 3 (CVB3), and either BALB/c
      (H-2d), MRL+/+ (H-2k), or DBA/2 (H-2d) male mice. Infection of all three mouse
      strains results in equivalent levels of myocardial inflammation 7 days later. IgG
      antibodies are detected by immunofluorescent staining in DBA/2 but not BALB/c or
      MRL+/+ myocardium and correlate with the detection of anti-heart antibodies in
      the sera of DBA/2 mice by immunofluorescence. CD4+ cell depletion of DBA/2 and
      MRL+/+ mice prevents myocarditis, but both CD4+ and CD8+ T cells cause cardiac
      inflammation in BALB/c mice, although CD8+ cells are substantially more
      pathogenic than CD4+ cells in this strain. No or few CD8+ T cells infiltrate the
      myocardium of either DBA/2- or MRL+/(+)-infected animals, although this is the
      predominant T-cell population in BALB/c mice. Apoptosis was measured by terminal
      deoxynucleotidyl transferase-staining of myocardial sections. No apoptosis was
      observed in inflamed DBA/2 hearts. Apoptosis was restricted to inflammatory cell
      infiltrates of infected MRL+/+ hearts, but apoptosis was wide-spread in both the
      inflammatory cell infiltrates and in myocytes outside inflammatory lesions in
      BALB/c mice. Atria natriuretic factor (ANF) mRNA expression was only elevated in
      the left ventricles of BALB/c mice. CD8+ T-cell depletion abrogated the
      appearance of apoptotic myocytes and ANF mRNA expression. The fact that
      ventricular ANF production often occurs during cardiac failure suggests that
      myocardial stress is substantially greater in BALB/c mice than in other strains
      despite equivalent amounts of cardiac inflammation.

PMID- 9166289
TI  - Cell-surface levels of human carcinoembryonic antigen are inversely correlated
      with colonocyte differentiation in colon carcinogenesis.
AB  - Human carcinoembryonic antigen (CEA) is overexpressed in a wide variety of
      epithelial malignancies including colon cancer. CEA can function in vitro as a
      homotypic intercellular adhesion molecule and can block the terminal
      differentiation of rodent myoblasts, thus raising the possibility that
      deregulated expression of CEA might directly contribute to malignant progression.
      To address this question, the expression pattern and cell-surface levels of CEA
      were studied during malignant transformation of the colonic epithelium in
      sporadic and familial adenomatous polyposis-related neoplasms. The level of
      immunohistochemically detected CEA was higher in 30% to 62% of microadenomas and
      small adenomas from familial adenomatous polyposis patients compared with
      adjacent normal mucosa, and this proportion was positively correlated with lesion
      size and degree of dysplasia. Cytofluorometric analysis of highly purified single
      epithelial cell suspensions from freshly excised carcinomas versus adjacent
      normal tissue demonstrated up to a 20-fold increase of mean cell-surface CEA in a
      group of colon carcinomas representative of the overall majority of such tumors-
      from Dukes' stages A to D and ranging mainly from well to moderately
      differentiated, the degree of overproduction was inversely correlated with tumor
      differentiation and directly correlated with stage. A marked tendency toward
      nonpolarized versus apical cell-surface expression with progression was also
      noted. Nonspecific cross-reacting antigen (NCA), a CEA family member, is also a
      homotypic adhesion molecule and blocks terminal myogenic differentiation, whereas
      biliary glycoprotein is a CEA family adhesion molecule that does not. Cell
      surface NCA showed even greater overexpression (up to 70-told) in
      dedifferentiated tumors, whereas total-cell biliary glycoprotein showed
      approximately 2-fold lower levels than was normal in more differentiated tumors
      and approximately 2-fold higher levels than in further progressed tumors. These
      results therefore support the suggestion that CEA and NCA can directly contribute
      to colon carcinogenesis by inhibiting colonocyte differentiation.

PMID- 9166290
TI  - Collagenase-3 (MMP-13) is expressed during human fetal ossification and re
      expressed in postnatal bone remodeling and in rheumatoid arthritis.
AB  - To explore possible physiologic functions for the metalloproteinase collagenase
      3, we have examined its temporal and spatial expression during human fetal
      development. Except for mesenchymal cells in the umbilical cord at 4 weeks of
      gestation, signal for collagenase-3 mRNA was confined to mineralizing skeletal
      tissue and detected in hypertrophic chondrocytes and osteoblastic cells involved
      in ossification beginning at 10 weeks and continuing through gestation. These
      cells were also immunoreactive with collagenase-3 antiserum, indicating their
      ability to produce collagenase-3 protein. In osteoblastic cells, the expression
      of membrane-type 1 metalloproteinase and 72-kd gelatinase mRNA, which have the
      capacity to activate collagenase-3 in vitro, colocalized with that of collagenase
      3. In postnatal tissues, collagenase-3 was re-expressed in processes involving
      skeletal remodeling, such as bone cysts and ectopic bone and cartilage formation.
      Multinucleated osteoclasts were consistently negative for collagenase-3.
      Furthermore, in patients with seropositive rheumatoid arthritis, expression of
      collagenase-3 was prominent in articular cartilage, and collagenase-3 protein was
      detected by immunoblotting in synovial fluids. Consistent with its substrate
      specificities, a plausible function for collagenase-3 in these processes is to
      preferentially degrade type II collagen, thus serving a role during primary
      ossification, in skeletal remodeling, and in destructive joint disease.

PMID- 9166291
TI  - Differential regulation of matrix metalloproteinases associated with aging and
      hypertension in the rat heart.
AB  - We compared two models of cardiac fibrosis in which collagen synthesis is
      controlled at different levels. Regulation is pretranslational in aldosterone
      salt-induced hypertension in young rats and posttranslational in 24-month-old
      rats. However, little is known about the role of matrix metalloproteinases (MMP)
      in fibrosis development. Ventricular MMP activities were studied by zymography,
      and MMP-2 and MMP-1 mRNA levels were determined using slot-blot and ribonuclease
      protection assay, respectively. After 1 month of aldosterone-salt treatment,
      proMMP-2, MMP-2, and proMMP-1 collagenolytic activities and their gene expression
      were unchanged compared with sham-operated rats. After 2 months, total MMP-2
      activity was increased by 40% with parallel stimulation of its gene expression.
      These changes were localized by in situ zymography within the media of coronary
      vessels. These results suggest that MMP play a prominent role in vascular
      remodeling during the first steps of hypertension. During aging, however, there
      were 40% and 45% decreases in MMP-2 and proMMP-1 activity, respectively, with a
      corresponding down-regulation of MMP-2 mRNA. These observations suggest that
      depression of the degradative pathway is partly responsible for age-associated
      fibrosis. Thus, MMP have differing involvements in the cardiac remodeling
      associated with hypertension or aging.

PMID- 9166292
TI  - Acquisition of TGF-beta 1 resistance: an important progression factor in human
      renal cell carcinoma.
AB  - The balance of growth regulation in tumors can be profoundly disturbed by defects
      in the transforming growth factor-beta 1 (TGF-beta 1) system. Thus far,
      investigations into the secretion of TGF-beta 1, the expression of its type I,
      II, and III receptors, as well as the functional intactness of the TGF-beta 1
      signal transduction pathways in human renal cell carcinomas (RCC) have been
      lacking. The objective of the present study, therefore, was to elucidate the role
      of the TGF-beta 1 system in RCC. We were able to determine the status of this
      system in 20 primary RCC and in 30 newly established human RCC cell lines of all
      major histologic types. All primary RCC showed expression of TGF-beta 1 and its
      type I and II receptors by immunohistochemistry, irrespective of histologic type.
      In vitro, all RCC cell lines secreted TGF-beta 1 protein as a biologically
      inactive complex, which cannot interact with cell-surface receptors. Type I ALK-5
      receptor mRNA and protein were detected in 29 RCC cell lines, whereas type I ALK
      2-receptor mRNA was found in all cell lines. Type II-receptor mRNA and protein
      could be demonstrated in all cell lines analyzed, and type III-receptor mRNA was
      observed in five RCC cell lines. Exogenously added, biologically active TGF-beta
      1 (1 ng/ml) resulted in significant (p < 0.05) inhibition of proliferation in 14
      of 30 RCC cell lines. Sixteen of thirty RCC cell lines, however, proved to be TGF
      beta 1-resistant. This resistance could not be explained by mutations in two "hot
      spot" regions of the type II-receptor gene (bp 622 to 795 and bp 1868 to 2019),
      as was demonstrated by DNA sequencing in the TGF-beta 1-resistant RCC cell lines.
      In conclusion, our observations are the first to provide evidence of an "escape"
      from the negative growth control of TGF-beta 1 by a significant proportion of
      RCC, suggesting that the acquisition of TGF-beta 1 resistance is an important
      progression factor for human RCC.

PMID- 9166293
TI  - Birth weight as a predictor of brachial plexus injury.
AB  - OBJECTIVE: To examine the relationship between birth weight and brachial plexus
      injury and estimate the number of cesareans needed to reduce such injuries.
      METHODS: All 80 neonatal records coded for brachial plexus injury from October
      1985 to September 1993 at the Brigham and Women's Hospital in Boston,
      Massachusetts, were studied along with linked maternal files. Birth weight,
      method of delivery, presence or absence of shoulder dystocia, and any diagnosis
      of maternal gestational or nongestational diabetes were abstracted. Data for the
      group with brachial plexus injury were compared with data for live-born infants
      without this injury during the same period. The sensitivity and specificity of
      birth weight as a predictor of brachial plexus injury were calculated. Further,
      the number of cesarean deliveries necessary to prevent a single brachial plexus
      injury was estimated using various weight cutoffs (4000, 4500, and 5000 g) for
      elective cesarean delivery. RESULTS: Among 77,616 consecutive deliveries, there
      were 80 brachial plexus injuries identified, for an incidence of 1.03 per 1000
      live births. The incidence of brachial plexus injury increased with increasing
      birth weight, operative vaginal delivery, and the presence of glucose
      intolerance. In the group of women without diabetes, between 19 and 162 cesarean
      deliveries would have been necessary to prevent a single immediate brachial
      plexus injury. Among women with diabetes, between five and 48 additional
      cesareans would have been required. CONCLUSION: Although birth weight is a
      predictor of brachial plexus injury, the number of cesarean deliveries necessary
      to prevent a single injury is high at most birth weights. Because of the large
      number of cesarean deliveries needed to prevent a single brachial plexus injury
      in infants born to women without diabetes, it is difficult to recommend routine
      cesarean delivery for suspected macrosomia in these women.

PMID- 9166294
TI  - Smoking in pregnancy, exhaled carbon monoxide, and birth weight.
AB  - OBJECTIVE: To examine the relation of cigarette consumption and exhaled carbon
      monoxide levels during pregnancy and to assess the effect of these smoking
      measures on birth weight. METHODS: Cigarette consumption and exhaled carbon
      monoxide levels were recorded at the first prenatal visit and the 36-week visit
      from women who smoked early in pregnancy. Analysis of variance was used to
      compare birth weights for differing levels of cigarette consumption and exhaled
      carbon monoxide. Correlation and regression analyses were used to estimate the
      effects of the smoking measures at both prenatal visits on birth weight. RESULTS:
      Cigarette consumption and exhaled carbon monoxide levels at both visits were
      associated significantly with birth weight. After the first prenatal visit, a
      reduction in cigarette consumption of at least nine cigarettes per day or in
      exhaled carbon monoxide of 8 parts per million (ppm) was associated with gains in
      birth weight of 100 g or more. The proportion of low birth weight (LBW) infants
      increased significantly with increasing levels of cigarette consumption and with
      increasing concentrations of exhaled carbon monoxide. CONCLUSION: Substantial
      reductions in cigarette consumption or in exhaled carbon monoxide levels after
      the first prenatal visit are needed to achieve gains in birth weight. Not
      smoking, or having an exhaled carbon monoxide level less than 5 ppm minimizes the
      likelihood of having an LBW infant.

PMID- 9166295
TI  - A scoring system for the prediction of successful delivery in low-risk birthing
      units.
AB  - OBJECTIVE: To establish and test the effectiveness of a low-risk scoring system
      to predict obstetric outcome for the selection of women suitable for confinement
      in low-intervention units. METHODS: Retrospective analyses were performed on data
      from 2900 women enrolled in the Western Australian Pregnancy Cohort Study and
      1353 women managed at a midwifery-based birth center. A combination of the
      principal predictors of obstetric outcome, incorporating a previously published
      scoring system and various clinical features, was used to exclude high-risk cases
      at 18 weeks' and 36 weeks' gestation. Stepwise multivariate logistic regression
      analyses of the remaining pregnancies then produced a low-risk scoring system.
      RESULTS: This system predicted a 55% chance of an uncomplicated delivery in a
      midwifery-based setting after allocating 54% of women to the low-risk category.
      It predicted an 82% chance of an uncomplicated delivery in a primary medical care
      setting with the allocation of 84% of women as low risk. CONCLUSION: The results
      of this study suggest that adding induction and augmentation of labor, together
      with low pelvic instrumental delivery, to the treatment options in a low
      intervention unit would raise the rate of successful confinement within the unit
      from 55% to 82%. Our scoring system now requires prospective evaluation to
      further assess its clinical value.

PMID- 9166296
TI  - Cost-effectiveness of strategies used in the evaluation of pregnancies
      complicated by elevated maternal serum alpha-fetoprotein levels.
AB  - OBJECTIVE: To perform a cost-effectiveness analysis of various protocols used in
      the diagnostic evaluation of pregnancies complicated by elevated levels of
      maternal serum alpha-fetoprotein (MSAFP). METHODS: The variables incorporated in
      this model were the prevalence of relevant fetal anomalies; the sensitivity and
      specificity of MSAFP at 2.0 or 2.5 multiples of the median (MoM); and the
      sensitivity, specificity, cost, and safety of targeted ultrasound and
      amniocentesis. We expressed the cost-effectiveness of each strategy as the total
      cost of the diagnostic evaluation divided by the number of anomalous fetuses
      identified, yielding the cost per identified anomalous fetus. RESULTS: In a
      hypothetical cohort of 100,000 singleton pregnancies, a strategy of targeted
      ultrasound for MSAFP of at least 2.0 MoM detected 90 of 110 structurally abnormal
      fetuses, without iatrogenic fetal loss, at a cost of $5700 per anomalous fetus. A
      strategy of amniocentesis with karyo-type determination for MSAFP of at least 2.5
      MoM detected 15 additional abnormal fetuses (87 structural abnormalities, ten
      autosomal aneuploidies, and eight sex chromosomal aneuploidies), with nine
      iatrogenic fetal losses, at an incremental cost of $46,100 per anomalous fetus.
      CONCLUSION: The increased cost and iatrogenic fetal loss rate may not justify the
      increased diagnostic yield of amniocentesis as compared with ultrasound in the
      evaluation of pregnancies complicated by elevated MSAFP.

PMID- 9166297
TI  - The association between hypertensive disorders of pregnancy and abnormal second
      trimester maternal serum levels of hCG and alpha-fetoprotein.
AB  - OBJECTIVE: To examine the association between hypertensive disorders of pregnancy
      and second-trimester maternal serum alpha-fetoprotein (MSAFP) and hCG levels.
      METHODS: The proportions of abnormal second-trimester MSAFP and hCG levels in the
      serum samples from 65 women with true pregnancy-induced hypertension or
      preeclampsia (cases) were compared to the proportions of abnormal levels in all
      1943 women without this disorder in the same cohort in a hospital setting.
      Maternal serum alpha-fetoprotein and hCG levels of the 65 cases also were
      compared to those of 325 completely uncomplicated matched control pregnancies,
      selected from the same cohort. Fisher exact test and Student t test were used for
      statistical analysis and P < .05 was considered statistically significant.
      RESULTS: An MSAFP level at least 2.5 multiples of the median (MoM) was found in
      two of 65 cases (3.1%) and in 27 of 1943 women (1.4%) in the rest of the cohort,
      a nonsignificant difference (relative risk [RR] = 2.2; P = .24). The statistical
      power to identify a significant difference for this RR was .27. An hCG level of
      at least 2.5 MoM was found in six cases (9.2%) and in 89 (4.6%) of women in the
      rest of the cohort, also a nonsignificant difference (RR = 2.0; P = .12). The
      statistical power to identify a significant difference for this RR was .38. The
      mean (+/-standard deviation) logarithms of the MSAFP and hCG MoMs in the 65 cases
      (0.039 +/- 0.191 and 0.048 +/- 0.265, respectively) were not significantly
      different from those in the 325 matched controls (0.006 +/- 0.148 and -0.010 +/-
      0.244, respectively; P = .12 and .08, respectively). CONCLUSION: Although a weak
      association cannot be excluded, this study found no clinically important increase
      in risk of developing subsequent hypertensive disorders of pregnancy among women
      with abnormal second-trimester levels of MSAFP or hCG.

PMID- 9166298
TI  - Intrapartum rupture of the unscarred uterus.
AB  - OBJECTIVE: To examine risk factors and maternal and neonatal outcomes in ten
      cases of intrapartum rupture of the unscarred uterus. METHODS: Uterine ruptures
      in women without previous cesarean deliveries were identified from an ongoing log
      for a 12-year period beginning January 1, 1983. Detailed information was obtained
      by review of hospital records. RESULTS: From January 1, 1983, through December
      31, 1994, we identified 13 uterine ruptures in women without previous cesarean
      deliveries. Three resulted from motor vehicle accidents and were excluded from
      analysis. Ten occurred during labor and are the subjects of our report. The
      incidence of intrapartum rupture of an unscarred uterus was 1 in 16,849
      deliveries. Associated factors included oxytocin use (four cases), prostaglandin
      use (three cases), use of vacuum or forceps (three cases), grand multiparity (two
      cases), and malpresentation (two cases). Intervention was prompted by fetal heart
      rate decelerations in seven cases and by severe hemorrhage in three. Uterine
      rupture was associated with acute abdominal pain in six cases, maternal
      tachycardia in five, and severe hypotension in two. Neonatal outcomes were normal
      in nine cases. There were no maternal or perinatal deaths. CONCLUSION:
      Intrapartum rupture of the unscarred uterus is a rare obstetric emergency.
      Maternal and perinatal outcomes are optimized by awareness of risk factors,
      recognition of clinical signs and symptoms, and prompt surgical intervention.

PMID- 9166299
TI  - Adverse perinatal outcome in parturients who use crack cocaine.
AB  - OBJECTIVE: To determine the risk of adverse pregnancy outcome among crack cocaine
      users in a large homogeneous prenatal population with objective documentation of
      drug use. METHODS: A retrospective cohort study was performed on a population of
      inner-city women who were offered routine voluntary urine drug screening and who
      delivered between January and December 1992 at a large county hospital. The study
      population consisted of 483 users (positive drug screens) and 3158 non-users
      (negative drug screens). Univariate analysis and multiple logistic regression
      were used to identify the relation between crack cocaine use and adverse
      perinatal outcome. RESULTS: Users were significantly more likely than nonusers to
      deliver low birth weight (LBW) infants (31.3% versus 14.9%; crude odds ratio [OR]
      2.6; 95% confidence interval [CI] 2.1, 3.2), growth-restricted infants (29.0%
      versus 13.0%; crude OR 2.7; 95% CI 2.2, 3.4), and preterm infants (28.2% versus
      17.1%; crude OR 1.9; 95% CI 1.5, 2.4). In addition, users were more likely to
      have abruptions (3.3% versus 1.1%; crude OR 3.0; 95% CI 1.6, 5.6) and infants
      with low 5-minute Apgar scores (7.9% versus 4.5%; crude OR 1.8; 95% CI 1.2, 2.7).
      After adjusting for confounders (including alcohol use and smoking), only the
      risks of LBW and fetal growth restriction (FGR) remained significant, with
      adjusted OR 1.6 (95% CI 1.03, 2.4) and adjusted OR 1.7 (95% CI 1.2, 2.3),
      respectively. Although there was no significant difference in the rate of low 5
      minute Apgar scores between users and non-users after controlling for
      confounders, users with a positive urine drug screen within 1 week of delivery
      were significantly more likely than non-users to deliver infants with low 5
      minute Apgar scores: crude OR 2.4; adjusted OR 2.0 (95% CI 1.1, 3.7). CONCLUSION:
      In this inner-city population, crack cocaine use is associated with adverse
      pregnancy outcomes, as noted by increased risks of LBW and FGR.

PMID- 9166300
TI  - Laparoscopic management of adnexal masses suspicious at ultrasound.
AB  - OBJECTIVE: To evaluate the laparoscopic management of adnexal masses suspicious
      at ultrasound. METHODS: In a prospective study, adnexal masses suspicious at
      ultrasound were managed by laparoscopy. Indications for laparotomy included
      general contraindications to laparoscopy, obviously disseminated ovarian cancer,
      and technically impossible laparoscopic treatment. After laparoscopic diagnosis,
      frozen sections were used to confirm a diagnosis of malignancy. Treatment was
      performed by laparoscopy whenever feasible. RESULTS: Over a 3-year period, 247 of
      the 599 adnexal masses (41.2%) treated in our department were suspicious or solid
      at ultrasound. Seventeen patients were evaluated by laparotomy and 230 by
      laparoscopy. Overall, 204 women (82.6%) were treated by laparoscopy, including
      seven of the 37 malignant tumors (18.9%) and 197 of the 210 benign masses
      (93.8%). One case of tumor dissemination occurred after a laparoscopic
      adnexectomy and morcellation of a grade 1 immature teratoma. CONCLUSION:
      Laparoscopic diagnosis of adnexal masses suspicious at ultrasound avoids many
      laparotomies for the treatment of benign masses and allows an improved inspection
      of the upper abdomen. The laparoscopic treatment of adnexal masses suspicious at
      surgery should be evaluated further in carefully designed prospective studies.

PMID- 9166301
TI  - A randomized comparison of continuous versus interrupted mass closure of midline
      incisions in patients with gynecologic cancer.
AB  - OBJECTIVE: To address the incidence of deep wound dehiscence and incisional
      hernia formation with two types of mass closure after vertical midline laparotomy
      performed in patients with gynecologic cancer. METHODS: Continuous and
      interrupted mass closures were compared randomly in 632 patients. Both methods
      were performed with absorbable material. Of the 614 subjects who could be
      evaluated, 308 underwent a continuous, non-locking closure with looped
      polyglyconate suture, and 306 were closed with interrupted polyglycolic acid
      according to the Smead-Jones technique. RESULTS: Three (1%) subjects with the
      continuous closure and five (1.6%) with the interrupted closure had an abdominal
      wound infection (P = .50). One patient whose incision was closed with continuous
      suturing had a deep wound dehiscence (without evisceration). The follow-up period
      was 6 months to 3 years. No patient had evidence of chronic sinus drainage.
      Thirty-two (10.4%) of the patients who had the continuous closure and 45 (14.7%)
      of those who were closed with the interrupted method had evidence of incisional
      hernia (P = .14). No hernia developed in any patient with a wound infection. Four
      (1.3%) hernias after the continuous closure and eight (2.6%) after the
      interrupted closure required surgical repair because of patient discomfort (P =
      .38). CONCLUSION: The interrupted closure was not superior to the continuous
      closure for short- and long-term wound security. The continuous method was
      preferable because it was more cost-efficient and faster.

PMID- 9166302
TI  - Increased prevalence of vulvovaginal condyloma and vulvar intraepithelial
      neoplasia in women infected with the human immunodeficiency virus.
AB  - OBJECTIVE: To compare the prevalence of human papillomavirus (HPV)-associated
      vulvovaginal lesions in human immunodeficiency virus (HIV)-positive and HIV
      negative women. METHODS: For this cross-sectional study, all participants
      received a complete gynecologic examination including colposcopic evaluation and
      a structured interview about sociodemographic characteristics and risk factors
      for vulvovaginal disease. In addition, HPV DNA was assayed for in cervicovaginal
      lavages using polymerase chain reaction. RESULTS: Vulvar and/or vaginal condyloma
      acuminata were detected in 22 of 396 (5.6%) HIV-positive and in 3 of 375 (0.8%)
      HIV-negative women (odds ratio [OR] 7.3, P < .001). High-grade vulvar
      intraepithelial neoplasia (VIN) was present in two of the HIV-positive and none
      of the HIV-negative women. Human immunodeficiency virus-positive women with
      condyloma or VIN were significantly more likely to have cervical intraepithelial
      neoplasia (33%) than those without vulvovaginal lesions (17%) (OR 2.9, 95%
      confidence interval [CI] 1.1, 74). In multivariate logistic regression analysis,
      both HIV seropositivity (adjusted OR 5.3, 95% CI 1.3, 35.3) and HPV infection
      (adjusted OR 6.1, 95% CI 1.7, 39.4) were associated with vulvovaginal condyloma.
      CONCLUSION: The prevalence of vulvovaginal condyloma was increased in HIV
      positive women even when controlling for HPV infection. Human papillomavirus
      associated disease was more likely to be multicentric and involve the vulva,
      vagina, and cervix in HIV-positive than HIV-negative women. Detection of high
      grade VIN in two of the HIV-positive women suggests that they may also be at risk
      for developing invasive vulvar carcinoma.

PMID- 9166303
TI  - Predicting the outcome of surgical treatment of vulvar vestibulitis.
AB  - OBJECTIVE: To identify predictive factors for success or failure of perineoplasty
      for severe vulvar vestibulitis. METHODS: Seventy-nine women with severe vulvar
      vestibulitis underwent perineoplasty by a single surgeon during 1992-1994. Sixty
      (76%) who experienced a complete response were compared with 19 (24%) who had an
      incomplete response. Using univariate and then multivariate (logistic regression)
      analysis, the two groups were compared with regard to preoperative demographic,
      social, and medical variables, as well as physical findings in the vestibule.
      RESULTS: The complete- and incomplete-response groups were similar in all
      comparisons except for constant vulvar pain of vestibular origin (in addition to
      dyspareunia) and the presence of symptoms since first coitus. On multiple
      logistic regression, these characteristics had odds ratios (and 95% confidence
      intervals) of 4.97 (1.49, 16.63) and 5.83 (1.74, 19.55), respectively.
      CONCLUSION: An incomplete response to perineoplasty may be anticipated in women
      with vulvar vestibulitis associated with dyspareunia since their first episode of
      intercourse and in those with associated persistent vulvar pain. Treatment
      approaches other than surgery should be considered for such patients.

PMID- 9166304
TI  - The minimum single oral metronidazole dose for treating trichomoniasis: a
      randomized, blinded study.
AB  - OBJECTIVE: To identify the minimum effective single oral dose of metronidazole
      for trichomoniasis. METHODS: Women attending an inner-city sexually transmitted
      disease clinic who had Trichomonas vaginalis vaginitis diagnosed by microscopy
      were recruited for this randomized, double-blind study. Subjects were given a 0.5
      , 1-, 1.5-, or 2-g single oral dose of metronidazole, taken under direct
      observation. Demographic information, symptoms, and clinical findings were
      collected from patient interviews, and physical examinations were conducted at
      the time of enrollment and at the follow-up visit. The primary outcome measure
      was treatment success at the follow-up visit, established by negative culture and
      microscopy. RESULTS: Three (1.8%) of the 167 women enrolled were excluded because
      of vomiting after taking metronidazole, and 66 (40%) of the 164 remaining
      subjects did not return for the follow-up visit. No associations were found
      between the proportion of subjects lost to follow-up and the characteristics of
      these subjects across assignment groups. The treatment success ratio was highest
      in subjects who received the 1.5-g dose (23, 85%), followed by the 2-g (16, 84%),
      1-g (18, 62%), and the 0.5-g dose (8, 35%). CONCLUSION: A single 1.5-g dose of
      metronidazole has efficacy equivalent to a single 2-g dose for the treatment of T
      vaginalis vaginitis.

PMID- 9166305
TI  - Screening for ectopic pregnancy in symptom-free women at increased risk.
AB  - OBJECTIVE: To determine the ectopic pregnancy rate among symptom-free women at
      increased risk undergoing a screening program involving transvaginal sonography
      and serum hCG testing. METHODS: Consecutive symptom-free women at increased risk
      for ectopic pregnancy were studied prospectively by transvaginal sonography and
      serum hCG measurement to detect ectopic pregnancy before the onset of symptoms.
      RESULTS: Between September 1993 and May 1996, 143 symptom-free pregnant women
      with pregnancies of a gestational age of less than 7 weeks were screened. Eight
      had ectopic pregnancies, 129 had intrauterine pregnancies, and six had
      trophoblast in regression. Among the eight women with ectopic pregnancies, one
      was initially diagnosed as having an intrauterine pregnancy. This women returned
      1 week later with abdominal pain, and an ectopic pregnancy with intra-abdominal
      bleeding was found. Ectopic pregnancies were present in 5.6% (95% confidence
      interval 2.5%, 10.7%) of the women screened. This was significantly lower than
      reported in a previous study. CONCLUSION: The ectopic pregnancy rate in the
      population that was offered screening was low. Thus, it is questionable whether
      the possible benefits (prevention of complications and reassurance of the woman)
      outweigh possible detriments (false-positive diagnosis, financial costs, and
      emotional stress that could be induced by screening.

PMID- 9166306
TI  - The reliability of performing a screening cystometrogram using a fetal monitoring
      device for the detection of detrusor instability.
AB  - OBJECTIVE: To determine if a cystometrogram performed using the intrauterine
      pressure channel of a fetal monitor can be used to screen for detrusor
      instability in women undergoing evaluation for urinary incontinence. METHODS:
      Sixty-six women with primary complaints of urinary incontinence were randomized
      to have a cystometrogram performed at their initial visit with a multichannel
      electronic cystometer or with the intrauterine pressure channel of a fetal
      monitor. Subjects underwent a second cystometrogram 1-4 weeks later with the
      alternative technique. The results were analyzed with chi 2 analysis and
      correlation coefficients. RESULTS: Twenty-two subjects had detrusor instability
      diagnosed by the multichannel electronic cystometer. The fetal monitor
      cystometrogram was 91% sensitive and 86% specific in detecting detrusor
      instability, and had a 77% positive predictive value and a 95% negative
      predictive value. The correlation coefficients between the two examinations for
      bladder volume at first sensation, maximum capacity, volume at first contraction,
      and intensity of uninhibited detrusor contraction were r = 0.51, r = 0.69, r =
      0.87, and r = 0.79, respectively; all of these were statistically significant.
      CONCLUSION: The intrauterine pressure channel of a fetal monitor can be used
      reliably to perform a cystometrogram to screen for detrusor instability in
      patients presenting with complaints of urinary incontinence.

PMID- 9166307
TI  - Effects of first-trimester fluoxetine exposure on the newborn.
AB  - OBJECTIVE: To determine whether first-trimester exposure to fluoxetine, a
      selective serotonin reuptake inhibitor commonly used to treat depression and
      obsessive-compulsive disorders, is associated with increased frequency of fetal
      malformations. METHODS: We evaluated outcomes of all pregnancies identified
      prospectively with confirmed first-trimester fluoxetine exposure contained in the
      Eli Lilly and Company worldwide fluoxetine pregnancy registry. These outcomes
      were compared with historic reports of newborn surveys. RESULTS: Outcomes were
      available for 796 pregnancies, 37 from fluoxetine clinical trials and 759 from
      spontaneous reports. Spontaneous abortions were reported in 110 of the 796
      (13.8%) pregnancies. Of the remaining 686, malformations, deformations, and
      disruptions, including those identified after the perinatal period, were reported
      in 34 (5.0%). No consistent or recurring pattern of abnormalities was observed.
      CONCLUSION: Based on comparison with historic reports of newborn surveys, it is
      unlikely that maternal fluoxetine use during the first trimester of pregnancy
      results in increased risk of fetal malformations.

PMID- 9166308
TI  - Performance of the dipalmitoyl phosphatidylcholine test in predicting respiratory
      distress syndrome in contaminated samples of amniotic fluid.
AB  - OBJECTIVE: To evaluate the reliability of the dipalmitoyl phosphatidylcholine
      test in predicting respiratory distress syndrome (RDS) in the presence of common
      contaminants of amniotic fluid. METHODS: Forty specimens of amniotic fluid
      collected within 72 hours of delivery were divided in five 25 microL aliquots and
      diluted with either phosphate-buffered saline (control), meconium, blood, vaginal
      fluid, or semen. The concentration of dipalmitoyl phosphatidylcholine in all five
      groups of samples, as measured by the dipalmitoyl phosphatidylcholine test, was
      compared by paired t test, Dunnett test, and analysis of variance, and correlated
      with the neonatal respiratory status of the newborns. RESULTS: No significant
      differences in the concentration of dipalmitoyl phosphatidylcholine were found
      between control and the corresponding contaminated samples (P = .33). Of the 200
      samples evaluated, 80 had dipalmitoyl phosphatidylcholine concentrations below 12
      micrograms/mL and 120 had at least 12 micrograms/mL. Using a cutoff dipalmitoyl
      phosphatidylcholine concentration of 12 micrograms/mL, the presence of RDS was
      predicted accurately in all 15 control and in 61 of 65 contaminated samples. The
      absence of RDS, as predicted by a dipalmitoyl phosphatidylcholine value at least
      12 micrograms/mL, was predicted accurately in 24 of 25 control samples and 96 of
      100 contaminated samples. The overall accuracy of the dipalmitoyl
      phosphatidylcholine test in predicting RDS in contaminated samples was 98%.
      CONCLUSION: The dipalmitoyl phosphatidylcholine test is a reliable predictor of
      RDS in contaminated samples.

PMID- 9166309
TI  - Amniotic fluid distribution in predicting perinatal outcome in patients with
      ruptured membranes.
AB  - OBJECTIVE: To determine if amniotic fluid distribution predicts perinatal outcome
      in women with spontaneously ruptured membranes. METHODS: Patients presenting for
      labor and delivery with spontaneously ruptured membranes had amniotic fluid
      indices determined upon admission. Those with greater than 50% of their amniotic
      fluid in the upper quadrants were placed in the upper-greater group and those
      with greater than 50% in the lower quadrants were placed in the lower-greater
      group. The groups were compared with respect to meconium staining, 1- or 5-minute
      Apgar scores below 7, persistent variable or late decelerations, umbilical
      arterial or venous pH below 7.20, cesarean for non-reassuring fetal heart rate
      monitoring, and neonatal intensive care unit admissions. RESULTS: One hundred
      women were studied, 60 in the upper-greater group and 40 in the lower-greater
      group. Significant differences between upper-greater and lower-greater
      distributions were noted in meconium staining (28.3% compared with 0%, P < .001),
      1-minute Apgar score below 7 (16.7% compared with 2.5%, P < .027), variable
      decelerations (63.3% compared with 25.0%, P < .001), late decelerations (23.3%
      compared with 0%, P < .001), and cesarean for non-reassuring fetal heart tracing
      (11.6% compared with 0%, P < .025). The negative predictive values for all of the
      variables studied were in the range 92.5-100%, with the exception of variable
      decelerations (75%). CONCLUSION: Amniotic fluid distribution predicts perinatal
      outcome in patients with ruptured membranes. This test's high negative predictive
      value indicates its potential as a valuable screening tool. These results may
      provide additional guidance in defining the intrapartum management of patients
      presenting with ruptured membranes.

PMID- 9166310
TI  - Human amniotic fluid motogenic activity for fetal alveolar type II cells by way
      of hepatocyte growth factor.
AB  - OBJECTIVE: To find out if hepatocyte growth factor (HGF) in amniotic fluid (HGF
      AF) has a direct effect on fetal lung development, we investigated the effects of
      AF as well as recombinant human HGF (rhHGF) on proliferation, migration, and
      morphogenesis of fetal alveolar type II cells in vitro. METHODS: Amniotic fluid
      samples were obtained from 37 women at various gestational ages. Mitogenic,
      motogenic, and morphogenic activity was investigated by 5-bromo-2'-deoxyuridine
      incorporation, Boyden chamber assay, and culture in collagen-gels, respectively.
      RESULTS: The motility of AK-D cells was stimulated by AF from 14 to 31 weeks'
      gestation in proportion to the concentration of HGF-AF, and this effect was
      comparable to that observed with rhHGF. Furthermore, this activity was
      neutralized by anti-human HGF antibody. However, AF samples subsequent to 32
      weeks had no motogenic influence despite the continued presence of immunoreactive
      HGF-AF. Neither increased DNA synthesis nor morphogenesis in response to AF was
      identified under the conditions used. CONCLUSION: The present study suggests that
      AF stimulates alveolar type II cell migration by way of HGF-AF in vitro.

PMID- 9166311
TI  - Iliac wing angle as a marker for trisomy 21 in the second trimester.
AB  - OBJECTIVE: To evaluate the fetal iliac wing angle in detecting trisomy 21 in the
      second trimester of pregnancy. METHODS: Using an axial view of the fetal pelvis,
      the angle between the right and left iliac wings (iliac wing angle) was measured
      ultrasonographically at the time of the second-trimester ultrasound or genetic
      amniocentesis in 377 singleton fetuses. Trisomy 21 was diagnosed by karyotype
      results from the amniocentesis or newborn examination with karyotype if trisomy
      21 was suspected based on phenotypic features. Sensitivity, specificity, and
      positive (PPV) and negative predictive values (NPV) were calculated using
      multiple cutoff points. A receiver operating characteristic (ROC) curve was used
      to identify the optimum iliac wing angle. Descriptive statistics and Student t
      test were utilized for analyses with a P of less than .05 considered significant.
      RESULTS: The average gestational age was 18.8 weeks (range 13-32). Karyotypes
      were available in 128 fetuses. The overall prevalence of trisomy 21 was 11 of 377
      (2.9%). The mean (+/-standard deviation) iliac wing angle in the normal fetuses
      was 68.2 degrees (+/-15.4 degrees) and 98.5 degrees (+/-11.3 degrees) in fetuses
      with trisomy 21 (P < .001). Using an ROC-derived absolute cutoff of 90 degrees,
      an abnormal iliac wing angle had sensitivity of 90.9% (ten of 11), specificity of
      94.5% (346 of 366), NPV of 99.7% (346 of 347), and PPV of 33.3% (ten of 30) to
      detect trisomy 21. CONCLUSION: Fetuses with trisomy 21 have greater iliac wing
      angles than do normal fetuses. Using an ROC-derived absolute cutoff of 90
      degrees, we could detect 90.9% of fetuses with trisomy 21 with a PPV of 33% in
      our high-risk population. These findings suggest that iliac wing angle is a
      useful marker in antenatal screening for trisomy 21.

PMID- 9166312
TI  - Transfer of erythropoietin across the placenta perfused in vitro.
AB  - OBJECTIVE: The purpose of this study was to investigate the placental passage of
      erythropoietin in a placental perfusion model ex vivo. METHODS: In an open system
      18 placentas were perfused on both the maternal and the fetal side.
      Erythropoietin and a reference substance were added to either the maternal or
      fetal perfusion medium. In the first series of experiments, radiolabeled
      erythropoietin was added to the perfusion medium in four different concentrations
      to help determine the transfer rate of erythropoietin. Based on the results of
      these experiments unlabeled erythropoietin was added to the perfusate in three
      different concentrations. Radiolabeled erythropoietin was used in addition to
      erythropoietin because measuring radioactivity in a gamma counter is less
      expensive than measuring by immunoassay. RESULTS: Accumulation of radioactivity
      in the venous portion of the fetal circuit was only 3.21% of the activity added
      to the maternal circuit. No evidence of transfer of erythropoietin to the
      contralateral compartment was noted, regardless of whether the test substance was
      added maternally or fetally. These results were independent of the concentration
      used. The reference compound antipyrine showed a mean transfer rate of 27.9%,
      which is in keeping with previous results. CONCLUSION: There is no transport of
      erythropoietin across fetal membranes. This finding is particularly remarkable in
      view of results published recently indicating the placenta as a site of
      erythropoietin production. The lack of its transport across the human placenta is
      most likely due to its high molecular weight.

PMID- 9166313
TI  - Digoxin-like immunoreactive substance and sodium-potassium-adenosine
      triphosphatase inhibition in normal pregnancy: a longitudinal study.
AB  - OBJECTIVE: To measure the levels of digoxin-like immunoreactive substance and
      digitalis-like factor bioactivity as manifested by sodium-potassium-adenosine
      triphosphatase (ATPase) inhibition throughout pregnancy. METHODS: Serum samples
      were collected from primigravidas in early (15 +/- 1.8 weeks), mid (26 +/- 1.2
      weeks), and late (36 +/- 1.1 weeks) gestation, as well as at 6 +/- 1.1 weeks
      postpartum (mean +/- standard error). Digoxin-like immunoreactive substance
      levels were determined by radioimmunoassay and digitalis-like factor bioactivity
      was determined by inhibition of ATPase. Data were analyzed by means of repeated
      measures analysis of variance. RESULTS: In 41 women with normal pregnancy
      outcomes, levels of digoxin-like immunoreactive substance rose progressively and
      significantly (P < .001) throughout pregnancy and returned to normal levels
      postpartum. Inhibition of ATPase activity also rose significantly (P < .004), but
      not as dramatically, during pregnancy and remained elevated 6 weeks postpartum.
      CONCLUSION: Although digoxin-like immunoreactive substance levels rise in
      pregnancy, functional digitalis-like factor activity, as manifested by inhibition
      of ATPase, does not parallel this rise strictly, implying that digoxin-like
      immunoreactive substance receptors may be reset during normal pregnancy. The
      enhanced cardiac performance that occurs in normal pregnancy may be mediated in
      part by increased digitalis-like factor activity.

PMID- 9166314
TI  - An increase of the plasma N-terminal peptide of proatrial natriuretic peptide in
      preeclampsia.
AB  - OBJECTIVE: To determine whether increased concentrations of the N-terminal
      peptide of proatrial natriuretic peptide and of atrial natriuretic peptide are
      related to the severity of preeclampsia and gestational hypertension. METHODS:
      Blood samples were collected from 70 healthy pregnant women, 48 women with
      preeclampsia, and 19 women with gestational hypertension in the third trimester.
      We used a specific radioimmunoassay (RIA) method suitable for the determination
      of the plasma N-terminal peptide of proatrial natriuretic peptide in unextracted
      plasma. The atrial natriuretic peptide was measured by RIA from Sep-Pak C18
      extracted plasma. RESULTS: The N-terminal peptide of proatrial natriuretic
      peptide levels were significantly higher in preeclamptic women than in healthy
      pregnant controls (median 571 [range 189-2000] versus 266 pmol/L [80-634], P <
      .001) and also significantly higher in women with severe preeclampsia than in
      women with mild preeclampsia (766 [431-2000] versus 492 pmol/L [189-1283], P =
      .01). The N-terminal peptide of proatrial natriuretic peptide values were
      significantly elevated in the subgroup of hypertensive pregnancies with abnormal
      Doppler velocimetry. At entry into the study the values for the N-terminal
      peptide of proatrial natriuretic peptide were higher in the subgroup of women who
      developed severe preeclampsia and/or gave birth to a small for gestational age
      (SGA) infant compared to the values in the subgroup of women in whom the
      hypertensive condition remained stable (710 [271-1475] versus 407 pmol/L [189
      1067], P = .006). Similar comparisons of atrial natriuretic peptide values did
      not reach significant differences. CONCLUSION: The levels of N-terminal peptide
      of proatrial natriuretic peptide were higher in women with preeclampsia than in
      those with gestational hypertension and higher in women with gestational
      hypertension than in those with normal pregnancies. A marked elevation in N
      terminal peptide of proatrial natriuretic peptide may predict development of
      severe preeclampsia and/or an SGA infant.

PMID- 9166315
TI  - The origin of endothelin-1 in patients with severe preeclampsia.
AB  - OBJECTIVE: To determine the site of origin of increased concentrations of plasma
      endothelin-1 in patients with severe preeclampsia. METHODS: Twelve patients with
      severe preeclampsia undergoing an indicated abdominal delivery had endothelin-1
      levels measured from plasma specimens drawn from right and left uterine and
      antecubital veins before delivery and after placenta removal with uterine
      curettage. Twelve uncomplicated control patients undergoing abdominal delivery
      had endothelin-1 concentrations drawn by an identical protocol. Clinical staff
      members were blinded to endothelin-1 results and laboratory staff were blinded to
      patient group assignment and sample source. Endothelin-1 plasma concentrations
      were determined by radioimmunoassay and data were analyzed by paired t test.
      RESULTS: No difference in endothelin-1 concentration was noted with respect to
      placental location, central versus peripheral, or predelivery versus postdelivery
      sampling procedures. Overall, patients with preeclampsia had higher plasma
      concentrations of endothelin-1 (mean 11.0 +/- 6.6 pg/mL) compared with
      normotensive patients (mean 8.4 +/- 6.7 pg/mL, P < .005). CONCLUSION: The
      decidual-placental interface does not appear to be the source of increased plasma
      endothelin-1 concentrations found in severe preeclampsia. The origin of this
      increase remains uncertain.

PMID- 9166316
TI  - A randomized trial of two vacuum extraction techniques.
AB  - OBJECTIVE: To determine whether two techniques of vacuum extraction delivery
      continuous vacuum and intermittent vacuum-have different effects on maternal
      fetal outcomes. METHODS: Patients to be delivered by vacuum extraction were
      randomized to receive continuous or intermittent vacuum. All deliveries were
      performed using the M-cup. In the continuous group, the level of vacuum was
      brought to 600 mmHg between contractions and was maintained at that level until
      delivery of the infant. Active efforts were made to prevent fetal loss-of-station
      between contractions by maintaining traction. In the intermittent group, the
      level of vacuum was decreased to 100 mmHg between contractions and no effort was
      made to prevent fetal loss-of-station. RESULTS: A total of 322 patients were
      randomized: 164 in the continuous arm and 158 in the intermittent group. The
      continuous method did not effect delivery faster (continuous 167 +/- 175 seconds
      versus intermittent 167 +/- 150 seconds; P = .97), nor did it lead to a reduction
      in method failures (continuous 12, intermittent nine; P = .72). The intermittent
      method did not appear to offer any benefit to the neonate regarding
      cephalhematoma formation (continuous 20, intermittent 17; P = .686) or any other
      measure of neonatal outcome. Maternal lacerations and episiotomy extensions were
      evenly distributed between the groups. Overall, the efficacy rate of the vacuum
      cup was 93.5% and the cephalhematoma rate was 11.5%. CONCLUSION: No differences
      in maternal or fetal outcome could be demonstrated if the level of vacuum was
      decreased between contractions or if an effort was made to prevent fetal loss-of
      station. The clinical results obtained in this trial using the M-cup are similar
      to the published results with the stainless-steel Malmstrom cup.

PMID- 9166317
TI  - Prenatal diagnosis of fetal primary cytomegalovirus infection.
AB  - OBJECTIVE: To evaluate the validity of prenatal diagnosis work-up for congenital
      cytomegalovirus (CMV) in women with primary infection. METHODS: Sixty-three
      pregnant women with primary cytomegalovirus disease (including two with twin
      pregnancies), referred to three tertiary perinatal centers over 4 years,
      underwent evaluation for congenital cytomegalovirus. Fetal diagnosis was made
      after 21 weeks' gestation by amniocentesis and fetal blood sampling (40
      subjects), or amniocentesis only (23 subjects). RESULTS: Twenty-two (35%)
      pregnancies showed evidence of vertical transmission: 13 of them underwent
      funipuncture, but only ten (77%) of the 13 showed positive immunoglobulin (Ig)-M
      results in fetal blood. No cases of positive fetal serum Ig-M with negative
      amniotic fluid culture or polymerase chain reaction were observed. In nine (41%)
      of the 22 pregnancies with evidence of vertical transmission, abnormal
      ultrasonographic findings were recorded. Six (27%) women with evidence of
      vertical transmission continued their pregnancies and in only one (with prenatal
      ultrasonographic abnormalities) was an infant born with neurologic sequelae. In
      41 (65%) pregnancies, no evidence of vertical transmission was found, and 37
      continued to term. Only one newborn from this subgroup subsequently showed mild
      motor disability during a median of 23 months of follow-up. CONCLUSION: Among
      pregnant patients with primary CMV infection, analysis of amniotic fluid detected
      all of the infected fetuses. Thus, this is a reliable tool for counseling
      pregnant women with primary infection. This may guide the patient as to whether
      or not pregnancy can be continued with a high level of confidence.

PMID- 9166318
TI  - Misoprostol for medical evacuation of early pregnancy failure.
AB  - OBJECTIVE: To determine whether misoprostol (a prostaglandin E1 analogue) 400
      micrograms orally (group 1) or 800 micrograms vaginally (group 2) will cause
      complete uterine evacuation in women with early pregnancy failure. METHODS:
      Twenty subjects were recruited for a prospective, non-blinded, randomized
      clinical trial. Early pregnancy failure was diagnosed by transvaginal ultrasound
      examination; only women with a closed cervical os and minimal vaginal bleeding
      were enrolled. Subjects returned 24 hours after misoprostol administration for a
      transvaginal ultrasound examination. If the gestational sac was still present,
      the misoprostol dose was repeated and the subject returned again 24 hours later.
      Subjects who failed to expel the pregnancy were offered a suction curettage.
      RESULTS: Twelve and eight women were randomized to groups 1 and 2, respectively.
      Complete uterine evacuation occurred in three of 12 [25%, 95% confidence interval
      (CI) 1%, 50%] and seven of eight (88%, 95% CI 65%, 100%, P = .010) subjects in
      groups 1 and 2, respectively. Vomiting occurred in 30% and 13%, respectively, and
      diarrhea in 50% and 38%, respectively. CONCLUSION: Vaginal misoprostol 800
      micrograms is more effective than oral misoprostol 400 micrograms for uterine
      evacuation of early pregnancy failure and may be an effective alternative to
      dilation and curettage.

PMID- 9166320
TI  - Routine endocrine screening for patients with karyotypically normal spontaneous
      premature ovarian failure.
AB  - OBJECTIVE: To evaluate the usefulness of routine screening for other associated
      autoimmune endocrine disorders in patients with karyotypically normal spontaneous
      premature ovarian failure. METHODS: One hundred nineteen women with
      karyotypically normal spontaneous premature ovarian failure (FSH exceeding 40
      mIU/mL) who desired fertility were evaluated at a tertiary care academic center
      by physical examination, measurement of serum free thyroxine and TSH, ACTH
      stimulation test, fasting serum glucose, 3-hour glucose tolerance test,
      measurement of serum electrolytes including total calcium, and measurement of
      serum vitamin B12. RESULTS: Twenty-two of 119 patients (18.5%) were known to have
      hypothyroidism and three were known to have Addison disease. Ten new cases of
      hypothyroidism and three new cases of diabetes mellitus were discovered. However,
      no new cases of adrenal insufficiency, hypoparathyroidism, or pernicious anemia
      were found. CONCLUSION: Screening for hypothyroidism and diabetes appears
      justified in those patients with karyotypically normal spontaneous premature
      ovarian failure who desire fertility. However, our findings suggest that in these
      patients, testing for other associated autoimmune endocrine disorders may be
      reserved for those with clinical indications.

PMID- 9166321
TI  - Evaluation of the postcoital test in cycles involving exogenous gonadotropins.
AB  - OBJECTIVE: To evaluate the hypothesis that a postcoital test, optimally performed
      in the periovulatory period of cycles in which gonadotropin-induced
      superovulation was used, correlates with cycle fecundity. METHODS: Of 1135 total
      consecutive cycles, 367 first cycles were analyzed from the reproductive
      endocrinology and infertility service of a university medical center. This
      referral population had a mean age of 34.6 years for the female partner, a
      nulliparity rate of 81%, and a mean length of infertility of 4.8 years.
      Postcoital tests were performed 36-40 hours after hCG administration in
      gonadotropin-stimulated cycles. Clinical pregnancy was defined as fetal cardiac
      activity as seen on transvaginal ultrasound examination. RESULTS: Couples with no
      sperm observed per high-power field in the cervical mucus achieved a 16%
      fecundity rate (21 pregnancies in 129 cycles), one to ten sperm a 18% fecundity
      rate (28 pregnancies in 154 cycles), and more than ten sperm a 15% fecundity rate
      (13 pregnancies in 84 cycles). There was no significant difference between groups
      (n = 367, P = .85); the power to detect a statistically significant difference
      was .82. As validation of optimal cervical mucus, fecundity rates were compared
      with these postcoital test values across the entire range of peak periovulatory
      serum estrogen levels, and no correlation was seen (P = .61, .86, and .96 for
      estrogen levels of 201-500, 501-1500, and 1501-3433 pg/mL, respectively).
      CONCLUSION: With precise periovulatory timing and supraphysiologic estrogen
      levels optimizing qualitative cervical mucus characteristics in gonadotropin
      induced cycles, the number of sperm observed per high-power field does not
      correlate with cycle fecundity.

PMID- 9166319
TI  - Serum levels of inhibin A and inhibin B in women with normal and abnormal luteal
      function.
AB  - OBJECTIVE: To determine whether serum inhibin A and inhibin B concentrations are
      lower in patients with luteal dysfunction than in women with normal luteal
      function. METHODS: Serum samples were collected from seven healthy women with
      regular menstrual cycles. Serum samples on days +5 to +9 after the LH surge were
      collected from patients with luteal dysfunction. The diagnosis of luteal
      dysfunction was based on a luteal phase duration less than 11 days and a single
      midluteal progesterone level below 10 ng/mL. Serum levels of inhibin A, inhibin
      B, progesterone, estradiol (E2), FSH, and LH were measured. RESULTS: The serum
      inhibin A levels were increased toward the late follicular phase. The levels
      reached a maximum during the midluteal phase, followed by a fall during the late
      luteal phase. The serum inhibin B levels were high during the follicular phases
      and the early luteal phase. The levels decreased during the midluteal and late
      luteal phases. Serum levels (mean +/- standard error of the mean) of inhibin A in
      patients with luteal dysfunction were significantly lower than those in women
      during the midluteal phase (26.2 +/- 2.9 compared to 41.9 +/- 2.8 pg/mL; P < .01)
      in addition to the expected decrease in serum progesterone levels (6.3 +/- 0.7
      compared to 14.7 +/- 1.2 ng/mL; P < .01). Serum inhibin B levels did not differ
      significantly between normal women and those with luteal dysfunction. There also
      were no significant differences in the E2, FSH, and LH levels. CONCLUSION: Levels
      of inhibin A, but not of inhibin B, may reflect the human luteal function.

PMID- 9166322
TI  - A profile of directors of clerkships in obstetrics and gynecology in the United
      States and Canada.
AB  - OBJECTIVE: To describe current professional activities, demographic profiles, and
      attitudes of directors of clerkships in university and community teaching sites.
      METHODS: Written surveys were mailed to departments of obstetrics and gynecology
      in the United States and Canada. Results were analyzed for differences in
      demographics, professional activities, and responses to statements describing
      career development of medical teachers and levels of institutional support.
      RESULTS: Responses from 132 of 148 (89%) medical schools and 67 of 96 (70%) known
      community-based clerkship directors showed no significant differences between the
      two groups in demographics or professional responsibilities. Three-quarters were
      men. The mean age was 47 years, mean duration as a faculty member 11 years, and
      mean tenure as clerkship director 8 years. One-half had been a clerkship director
      less than 5 years. The average clerkship director reported working approximately
      56 hours per week, of which 44% was devoted primarily to patient care, 24% to
      teaching, and 18% to administration. These faculty members describe the
      activities of their position as fulfilling and worthy of recognition in the
      academic promotions process. CONCLUSION: Directors of clinical clerkships in
      obstetrics and gynecology in both university- and community-based programs spend
      about one-half of their time in teaching and administration. They find their work
      fulfilling and worthwhile. Profiles are consistent over time and comparable to
      those described by clerkship directors in other specialties.

PMID- 9166323
TI  - Medical abortion in early pregnancy: a review of the evidence.
AB  - OBJECTIVE: To review the literature on medical abortion in early pregnancy. DATA
      SOURCES: I performed a MEDLINE search, supplemented by bibliographies of articles
      and textbooks. In addition, investigators in the field were consulted to identify
      other sources. The review was limited to reports in English or French concerning
      antiprogestins or methotrexate used either alone or in combination with a
      prostaglandin. METHODS OF STUDY SELECTION: Only those mifepristone studies with
      100 or more participants were included. Those participants who received the
      prostaglandin sulprostone were excluded because this drug is no longer used with
      mifepristone. Methotrexate studies of any size were included. All reports were
      categorized by study type, and the evidence was evaluated using the U.S.
      Preventive Services Task Force rating system. TABULATION, INTEGRATION, AND
      RESULTS: Both mifepristone and methotrexate, when used with a prostaglandin, can
      induce abortion safely in early pregnancy. Class I evidence supports a class A
      (good) recommendation that oral, single mifepristone doses of 200 mg and 600 mg
      have similar efficacy when used with a prostaglandin. Sequential and single-dose
      regimens have comparable efficacy. Vaginal misoprostol at 800 micrograms as an
      augmenting agent appears superior to the same dose given orally. With
      methotrexate abortion, 800 micrograms of misoprostol given vaginally 7 days after
      methotrexate is superior to the same dose given 3 days after. In addition,
      methotrexate in combination with misoprostol is more effective than misoprostol
      alone. CONCLUSION: Medical abortion with mifepristone or methotrexate in
      combination with a prostaglandin is safe and effective. However, the risk of
      hemorrhage and gastrointestinal side effects is greater with medical abortion
      than with suction curettage. Further research should be done to compare
      mifepristone and methotrexate abortions, to determine the upper gestational age
      limit, and to find the best way to provide this service in the U.S. health care
      system.

PMID- 9166324
TI  - Permanent Erb palsy: a traction related injury?

PMID- 9166325
TI  - Fetal recoil during labor to evaluate fetal well-being when heart rate monitoring
      is not informative.
AB  - BACKGROUND: Fetal movement is a predictor of fetal well-being. Fetal movement in
      response to a stimulation (fetal recoil) has been tested, and all fetuses that
      demonstrated recoil had umbilical arterial blood pH at least 7.20. CASES: We used
      fetal recoil to allow labor in three women with fetal heart tracings that were
      not informative. In all three, Apgar scores or umbilical artery pH values
      confirmed normal fetal acid-base status at birth. CONCLUSION: Fetal recoil is a
      potentially useful method to assess fetal status when fetal heart rate monitoring
      is not informative.

PMID- 9166327
TI  - Autosomal dominantly inherited Diamond-Blackfan anemia resulting in nonimmune
      hydrops.
AB  - BACKGROUND: Autosomal dominant inheritance of Diamond-Blackfan syndrome has been
      considered an uncommon occurrence. The onset of anemia is characteristically
      within the first year of life, with 10% of cases presenting at birth. Hydrops
      fetalis has been reported rarely. CASES: Two women with Diamond-Blackfan anemia
      had uncomplicated pregnancies without important exacerbation of their anemia.
      Each delivered an edematous infant affected with Diamond-Blackfan anemia, both of
      whom required immediate transfusions. One infant is currently 7 years old with
      transfusion-dependent Diamond-Blackfan anemia. The second infant died 2 days
      after birth; autopsy showed severe erythroid hypoplasia with absence of
      extramedullary hematopoiesis and placental villous edema. CONCLUSION: Diamond
      Blackfan anemia may result in severe fetal anemia requiring transfusion. Among
      women with this disorder, a greater percentage than previously suspected are at
      risk for having an infant with substantial anemia in both the fetal and perinatal
      periods. Because the penetrance of the disorder is variable, pregnant women with
      a history of Diamond-Blackfan anemia should be considered at risk.

PMID- 9166326
TI  - Antepartum fetal cerebral hemorrhage not predicted by current surveillance
      methods in cholestasis of pregnancy.
AB  - BACKGROUND: The reason for increased fetal mortality in cholestasis of pregnancy
      is not completely understood. Intracerebral hemorrhage due to coagulation
      disorders, similar to those reported in the mother, is a possible explanation.
      CASE: Antepartum fetal death occurred at 37 weeks in a primigravida with
      cholestasis of pregnancy. The woman was taking no medication. Autopsy revealed
      extensive cerebral hemorrhage. A cardiotocogram and biophysical profile performed
      24 hours and 5 days, respectively, before fetal death had been normal.
      CONCLUSION: Antepartum fetal death may occur in patients with mild cholestasis
      who are taking no medication. Intracerebral hemorrhage is a possible cause, and
      this may be unpredictable with current methods of fetal surveillance. This
      possibility constitutes an argument in support of delivering these pregnancies as
      soon as lung maturity is achieved.

PMID- 9166328
TI  - Intrapericardial teratoma in a twin fetus: diagnosis and management.
AB  - BACKGROUND: A rare cause of hydrops fetalis, intrapericardial teratoma is
      invariably associated with a pericardial effusion. In fetal life, the effusion or
      mass effect may cause cardiac tamponade, hydrops, and death. After delivery,
      ventilation and cardiac output may be compromised. CASE: One fetus of twins was
      diagnosed at 20 weeks' gestation with an intrapericardial teratoma. The affected
      twin underwent two intrauterine pericardiocentesis and had the tumor resected
      after delivery at 35 weeks' gestation. One year later, both twins are alive and
      well and have no evidence of tumor recurrence. CONCLUSION: Pericardiocentesis for
      tamponade secondary to a fetal intrapericardial teratoma, even when complicating
      a twin pregnancy, may prevent fetal death and allow delay of delivery until
      adequate fetal lung maturity has been achieved.

PMID- 9166329
TI  - False-positive diagnosis of spina bifida in a fetus with triploidy.
AB  - BACKGROUND: Neural tube defects can be difficult to diagnose using ultrasound.
      Cranial markers, such as the lemon and banana signs, are useful sonographic
      findings that alert the ultrasonographer to examine the spine more carefully. The
      false-positive rate for the banana sign has been reported previously as zero.
      CASE: A patient with elevated maternal serum alpha-fetoprotein presented for a
      fetal ultrasound examination. Findings on the scan included a lemon sign, a
      banana sign, an effaced cisterna magna, and splayed lumbar vertebrae. After
      pregnancy termination, no spinal abnormality was detected on autopsy. X-rays of
      the fetal spine demonstrated narrowing in the thoracic spine. The karyotype of
      the fetus was 69,XXY. CONCLUSION: The sonographic cranial findings suggestive of
      a neural tube defect were misleading in this case.

PMID- 9166330
TI  - The umbilical pump: a contributor to twin-twin transfusion.
AB  - BACKGROUND: Umbilical vascular coiling may function as a rudimentary pump that
      facilitates venous return from the placenta. CASES: Three consecutive twin
      gestations with twin-twin transfusion syndrome were evaluated prospectively at
      delivery. The birth weights and umbilical coiling indices of donor and recipient
      twins were compared. The umbilical coiling index was determined by dividing the
      number of complete vascular coils in a given umbilical cord by the cord's length
      in centimeters. In each case, the recipient twin was larger at birth and had an
      umbilical coiling index value that was at least twice that of the corresponding
      donor twin. CONCLUSION: Differential umbilical vascular coiling densities among
      monochorionic twins may play a role in the pathogenesis of twin-twin transfusion
      syndrome.

PMID- 9166331
TI  - External cephalic version of twin A.
AB  - BACKGROUND: When a first twin presents as a breech, cesarean delivery is
      generally recommended. Vaginal delivery of the first twin as a breech has also
      been described. However, the option of external cephalic version of the first
      twin, followed by vaginal delivery, is rarely considered. CASES: We report two
      cases in which twin A presented as a breech, one at 36 and one at 38 weeks'
      gestation. In each case, external cephalic version of the first twin was
      successful, with subsequent vaginal delivery of both twins. CONCLUSION: External
      cephalic version of a malpresenting first twin is a management option that can
      result in successful vaginal delivery.

PMID- 9166332
TI  - Diabetes insipidus in pregnancy: a treatable cause of oligohydramnios.
AB  - BACKGROUND: Diabetes insipidus, which presents with polyuria, polydipsia, and
      profound electrolyte abnormalities, occurs rarely in pregnancy. We report a
      patient with severe oligohydramnios that resolved after treatment of diabetes
      insipidus. CASE: A 14-year-old girl was admitted at 33 weeks' gestation with
      cramping and vaginal spotting. A sonogram indicated oligohydramnios and an
      amniotic fluid index (AFI) of 2.6, with normal fetal kidneys and bladder. On
      hospital day 2, the AFI was 0.0. Recorded fluid was 8 L in and 13.6 L out. Serum
      sodium was 153 mEq/L. Diabetes insipidus was diagnosed and treated with
      intranasal desmopressin acetate. The oligohydramnios resolved rapidly, and the
      patient delivered a healthy 2700-g male infant at 38 weeks. CONCLUSION: Although
      rare, diabetes insipidus may present initially in pregnancy and should be
      considered in patients with oligohydramnios. Simple diagnosis with determination
      of 24-hour urine volume and serum electrolytes can identify this potentially
      reversible cause of oligohydramnios and poor obstetric outcome.

PMID- 9166333
TI  - Pregnancy and delivery in a patient with mutilating dystrophic epidermolysis
      bullosa (Hallopeau-Siemens type).
AB  - BACKGROUND: Epidermolysis bullosa dystrophica of the mutilating Hallopeau-Siemens
      type is a rare inherited skin disease. Those afflicted have blisters and
      pronounced scarring of skin and mucous membranes after minor trauma. Pregnancies
      are very rare in affected women. CASE: A 24-year-old woman, gravida 1, with a
      severe form of the Hallopeau-Siemens type was monitored closely during pregnancy.
      The patient spontaneously delivered a healthy female neonate at term. Episiotomy
      wound healing was uncomplicated. Seven months later, she returned in her second
      pregnancy, which was complicated by mild anemia and polyhydramnios from possible
      gestational-onset diabetes mellitus. Again, vaginal delivery of a healthy neonate
      was performed at term. We did not observe pregnancy-induced exacerbations of the
      skin disease. CONCLUSION: Women with epidermolysis bullosa dystrophica of the
      Hallopeau-Siemens type may decide to have children after careful evaluation of
      the degree of impairment and a thorough explanation of the risks associated with
      pregnancy and delivery. Close monitoring of the pregnant patient is important.
      Vaginal delivery should be the first choice. Breast-feeding is difficult, but not
      contraindicated.

PMID- 9166334
TI  - Lumbar disk disease in pregnancy.
AB  - BACKGROUND: Lumbar disk herniation is rare in pregnancy. We report on three
      pregnant women with this disorder seen over 2 years. CASES: Three women were seen
      with progressive back pain, paresthesias, and urinary retention. In all three
      cases, magnetic resonance imaging confirmed the diagnosis. All failed
      conservative treatment and required surgery. All did well postoperatively, with
      improvement of symptoms and delivery at or near term. CONCLUSION: Lumbar disk
      herniation should be considered in pregnant women presenting with considerable
      back or leg pain. Magnetic resonance imaging is a useful diagnostic tool. Most
      patients can be treated conservatively, but those with incapacitating pain,
      progressive neurologic deficits, or bowel or bladder dysfunction may require
      surgical treatment.

PMID- 9166335
TI  - Opioid-induced rigidity after intravenous fentanyl.
AB  - BACKGROUND: Large doses of intravenous opioids may cause severe rigidity and
      prevent spontaneous or controlled ventilation. The mechanism of this effect
      appears to be neuraxis dopamine antagonism. Rigidity after analgesic doses of
      fentanyl has not been reported previously. CASE: A pregnant woman receiving
      haloperidol for multiple psychiatric conditions presented for evaluation of
      vaginal bleeding. Intravenous fentanyl was administered to facilitate vaginal
      examination. Severe rigidity of the extremities and truncal region occurred,
      which prevented spontaneous or assisted ventilation. CONCLUSION: Opioid
      administration may result in rigidity and respiratory embarrassment. Decreased
      analgesic requirements in pregnancy and concomitant butyrophenone administration
      may predispose to opioid-induced rigidity.

PMID- 9166336
TI  - Vaginal cavernous hemangioma in pregnancy.
AB  - BACKGROUND: Cavernous hemangioma of the vagina during pregnancy is extremely
      rare. No cases have been reported in the literature over the past 3 decades.
      CASE: A 32-year-old multipara presented at 37 weeks' gestation with a history of
      a vaginal mass growing rapidly over a 24-hour period. The vaginal outlet was
      obstructed by an infected and necrotic mass that was excised surgically. The
      patient was placed on bed rest and tocolytic therapy. She delivered vaginally at
      40 weeks' gestation without complications. CONCLUSION: Surgical management of a
      vascular vaginal tumor is possible in pregnancy. Excessive operative blood loss
      and consumptive coagulopathy are potential complications associated with
      cavernous hemangiomas.

PMID- 9166337
TI  - All-trans retinoic acid for the treatment of acute promyelocytic leukemia in
      pregnancy.
AB  - BACKGROUND: Acute promyelocytic leukemia, a subset of acute myelogenous leukemia,
      is commonly associated with disseminated intravascular coagulation (DIC). All
      trans retinoic acid is effective in the treatment of acute promyelocytic leukemia
      and may prevent an exacerbation of DIC. There is limited information, however,
      regarding the use of this agent in pregnancy. CASE: A 29-year-old woman with
      acute promyelocytic leukemia and DIC at 24 weeks' gestation was treated
      successfully with all-trans retinoic acid during the pregnancy, delivering a
      viable, normal infant at 33 weeks. CONCLUSION: This case illustrates the
      successful use of all-trans retinoic acid in pregnancy for the treatment of acute
      promyelocytic leukemia. With the combined, intensive efforts of the perinatal,
      neonatal, and hematology-oncology services, a favorable outcome was achieved.

PMID- 9166338
TI  - Rhabdomyosarcoma treated with chemotherapy during the third trimester.
AB  - BACKGROUND: Rhabdomyosarcoma is an aggressive tumor that is rarely found in
      pregnancy, and is usually treated with multiagent chemotherapy. Chemotherapy
      given during pregnancy is associated with several maternal-fetal complications,
      including risks for mutagenicity, myelosuppression, and fetal death. CASE: An 18
      year-old woman had stage III facial rhabdomyosarcoma diagnosed early in the third
      trimester. She achieved clinical remission with multiagent chemotherapy given
      during pregnancy, with no fetal complications. CONCLUSION: Invasive
      rhabdomyosarcoma is biologically predisposed to metastasize, and in the absence
      of effective chemotherapy, most patients will develop sites of distant
      recurrence. Chemotherapy plays an important role as frontline treatment in
      pregnant women with rhabdomyosarcoma.

PMID- 9166339
TI  - Uterine rupture during induction of labor at term with intravaginal misoprostol.
AB  - BACKGROUND: Misoprostol (prostaglandin E1) compares favorably with dinoprostone
      (prostaglandin E2) and oxytocin for labor induction at term. Excessive uterine
      activity has been reported using high-dose regimens, but no negative effect on
      outcomes has been observed. CASE: Labor was induced in a 34-year-old multipara at
      39 weeks' gestation using intravaginal misoprostol tablets. Five hours after
      administration of the second 25-microgram dose, fetal bradycardia prompted
      emergency cesarean delivery. Hysterectomy and left salpingo-oophorectomy were
      necessary to control bleeding from a 15-cm posterior uterine wall rupture.
      CONCLUSION: Misoprostol can cause excessive uterine activity and uterine rupture.

PMID- 9166340
TI  - Placenta previa percreta with bladder invasion.
AB  - BACKGROUND: Although the clinical presentation and imaging techniques can raise
      suspicion for placenta previa percreta, this potentially catastrophic condition
      may remain undiagnosed or its extent underappreciated until delivery. The
      decision to proceed with definitive surgery in cases of placenta previa percreta
      should be carefully considered. CASE: A case of placenta previa percreta with
      bladder invasion was diagnosed prenatally. This case illustrates the magnitude of
      complications that can arise despite aggressive multidisciplinary perioperative
      management. CONCLUSION: When possible, hysterectomy performed for placenta previa
      percreta is best avoided under anything other than ideal conditions. A
      multidisciplinary approach for preoperative, intraoperative, and postoperative
      management of placenta previa percreta optimizes maternal outcome.

PMID- 9166341
TI  - Postpartum endometritis caused by herpes simplex virus.
AB  - BACKGROUND: Herpes simplex virus (HSV) is rarely the causative agent of
      endometritis and is usually found in association with pelvic inflammatory
      disease. Only one case of postpartum HSV endometritis has been reported. CASES:
      We describe two cases of herpes simplex postpartum endometritis. Neither patient
      had genital HSV lesions noted at the time of delivery. The first case developed
      after a preterm cesarean delivery in an 18-year-old primipara. She had persistent
      puerperal fever despite broad-spectrum anti-microbial treatment. The second case
      was a 16-year-old primipara whose vaginal delivery was complicated by severe
      postpartum endometritis. Vulvar and endometrial cultures were positive for HSV
      alone in both patients. Both infants died from disseminated HSV infection.
      CONCLUSION: Herpes simplex virus can cause clinical postpartum endometritis.

PMID- 9166342
TI  - Factor V deficiency and menstruation: a gynecologic challenge.
AB  - BACKGROUND: Menorrhagia is a well-known complication of factor V deficiency.
      CASE: A 13-year-old girl with factor V deficiency presented with acute hemorrhage
      on day 4 of menses. Laboratory assessment revealed a hemoglobin of 36 g/L. The
      ultrasound appearance of a large loculated cystic mass was consistent with
      substantial intraperitoneal bleeding. Stabilization with blood products was
      followed by GnRH agonist therapy. Medical management was instituted effectively.
      Continued compliance with medication is essential to prevent recurrences.
      CONCLUSION: Factor V deficiency is rare. Coagulation disorders of this nature
      pose a challenge to gynecologists involved in patient management at the time of
      menses.

PMID- 9166343
TI  - Vaginal bleeding in an infant secondary to sliding inguinal hernia.
AB  - BACKGROUND: Vaginal bleeding in infancy is rare and, to our knowledge, has not
      been reported in association with an inguinal hernia. CASE: A premature infant
      with a known reducible inguinal hernia developed vaginal bleeding at 8 months.
      Work-up revealed no coagulopathy and no endocrine abnormality. Physical
      examination and ultrasound found no anatomic lesion responsible for her bleeding.
      At surgery, she was found to have an indirect hernia in which the uterus,
      fallopian tube, and ovary were sliding components. Her vaginal bleeding ceased
      after herniorrhaphy. CONCLUSION: Vaginal bleeding in a child with an inguinal
      hernia may occur when the uterus is a sliding component of the hernia.

PMID- 9166344
TI  - Disseminated Histoplasma capsulatum infection presenting as genital ulcerations.
AB  - BACKGROUND: Histoplasma capsulatum infection in adults is most often subclinical
      but can result in disseminated disease with weight loss, fever,
      hepatosplenomegaly, and oropharyngeal ulcerations. Genital ulceration as the
      presenting sign of the disease has been reported rarely. CASE: A 63-year-old
      woman presented with multiple vaginal ulcerations due to chronic disseminated H
      capsulatum infection. Initial diagnosis was made by Papanicolaou and Giemsa
      stained vulvar smears. Ketoconazole therapy resulted in clearing of the lesions
      in 5 weeks. CONCLUSION: Chronic disseminated histoplasmosis is an insidious and
      potentially fatal disease that can present rarely as genital mucocutaneous
      ulcerations in women. Prompt presumptive diagnosis can be accomplished by
      examination of smears obtained by ulcer abrasion, permitting institution of
      appropriate therapy.

PMID- 9166345
TI  - Incisional hernia after suprapubic catheterization.
AB  - BACKGROUND: Suprapubic catheterization is a popular method of bladder drainage
      after gynecologic surgery. We report two cases of incisional hernia that
      developed after suprapubic catheterization. CASES: The first case involved a 64
      year-old woman who underwent Burch urethropexy. Her suprapubic catheter was not
      removed until postoperative day 55 because of prolonged retention. She presented
      1 month later with abdominal pain. In the second case, a 65-year-old woman had
      vesicovaginal fistula repair with suprapubic catheterization for 2 weeks after
      surgery. Five months later, she presented with abdominal pain. In both cases,
      examination revealed a hernia at the catheter exit site. CONCLUSION: Incisional
      hernia is a rare complication of suprapubic catheterization that should be
      considered in patients who present with abdominal discomfort some time after
      catheterization.

PMID- 9166346
TI  - Uterine problems discovered after presumed hysterectomy: the Manchester operation
      revisited.
AB  - BACKGROUND: The Manchester operation consists of amputation of the cervix,
      leading some patients to believe that they have undergone a hysterectomy. CASES:
      A 69-year-old woman with vaginal discharge proved to have a well-differentiated
      adenocarcinoma in the retained uterine corpus. Another 69-year-old woman with a
      central fluid-filled pelvic mass proved to have a retained blood-filled corpus
      with an early-stage fallopian tube cancer. The third patient was a 90-year-old
      woman with symptoms of constipation and urinary frequency, who was found to have
      a large fluid-filled central mass. At surgery, the retained corpus was distended
      and filled with mucoid material. CONCLUSION: Patients who have undergone a
      Manchester operation may develop disease in the retained uterine corpus, which
      should be considered in the differential diagnosis of a pelvic mass.

PMID- 9166347
TI  - Vulvar keratoacanthoma.
AB  - BACKGROUND: Keratoacanthomas are neoplastic proliferations of keratinocytes
      thought to originate from follicular epithelium. There is only one previously
      reported case in which keratoacanthoma involved the vulva. CASE: A 54-year-old
      woman presented with a nonulcerated vulvar lesion of approximately 1 month's
      duration. The lesion was 1 cm in diameter, located on the mid-right labium majus,
      with no surrounding induration or hyperkeratosis. The patient underwent wide
      local excision and the clinical-pathologic diagnosis was keratoacanthoma. After 2
      years, she remains free of vulvar recurrence. CONCLUSION: Because of similarities
      in clinical presentation and histology to squamous cell carcinoma, the diagnosis
      of keratoacanthoma can be challenging. History and physical examination findings
      should be correlated with the histologic diagnosis, with consideration for
      dermatopathology consultation.

PMID- 9166348
TI  - Regression of uterine low-grade smooth-muscle tumors metastatic to the lung after
      oophorectomy.
AB  - BACKGROUND: Metastatic uterine low-grade smooth-muscle tumors may present with
      pulmonary symptoms and radiographic lung abnormalities consistent with metastatic
      neoplasms. Ovarian hormone stimulation of these smooth-muscle tumors has been
      suggested, but the role of surgical or medical oophorectomy has not been
      established in patients with metastatic disease. CASES: Two women with
      histologically confirmed uterine low-grade smooth-muscle tumors metastatic to the
      lung had progressive and complete tumor regression after oophorectomy and no
      further therapy. CONCLUSION: Some uterine low-grade smooth-muscle tumors
      metastatic to the lung regress after oophorectomy. Removing ovarian hormone
      stimulation may result in complete tumor regression without the need for further
      therapy.

PMID- 9166349
TI  - Uterine leiomyoma particle growing in an abdominal-wall incision after
      laparoscopic retrieval.
AB  - BACKGROUND: As laparoscopic myomectomy gains acceptance among patients and pelvic
      surgeons, new laparoscopic techniques create a risk for complications that were
      not encountered in classic laparotomy myomectomy. Report of such complications
      will allow surgeons to undertake appropriate steps to prevent them. CASE:
      Fragments of uterine leiomyomas unintentionally implanted and growing in
      abdominal-wall incisions after laparoscopic myomectomy presented clinically with
      incisional pain and an abdominal-wall mass of increasing size. Diagnosis was
      confirmed by the histology, and treatment was achieved by excision. CONCLUSION:
      In the differential diagnosis of a progressively increasing incisional mass and
      pain after laparoscopic myomectomy, inadvertent implantation and growing
      particles of uterine leiomyomas should be considered when fragmented tumors are
      removed through a trocar sleeve.

PMID- 9166350
TI  - Recurrent ovarian tumor with low malignant potential and cardiac metastasis.
AB  - BACKGROUND: Up to 20% of ovarian epithelial tumors are classified as being of low
      malignant potential. Most of these low malignant potential tumors are detected at
      an early stage and have an excellent prognosis. This is a report of a woman with
      cardiac metastasis from an ovarian low malignant potential tumor. CASE: This case
      describes a 53-year-old woman who presented with congestive heart failure and was
      found to have a recurrent stage III ovarian tumor of low malignant potential. A
      transesophageal echocardiogram revealed compression of the inferior vena cava and
      a mass encompassing the right atrium. Findings at autopsy confirmed a low
      malignant potential ovarian tumor thrombus involving the inferior vena cava and
      right atrium. CONCLUSION: Ovarian low malignant potential tumors can metastasize
      in an aggressive manner. A transesophageal echocardiogram may be useful when the
      diagnosis of cardiac tumor thrombus is considered.

PMID- 9166351
TI  - Gravid uterine rupture after myolysis.

PMID- 9166352
TI  - Successful pregnancy outcome in a patient with both congenital hypofibrinogenemia
      and protein S deficiency.

PMID- 9166353
TI  - Successful management of pregnancy in a patient with von Willebrand disease
      Normandy.

PMID- 9166354
TI  - Niemann-Pick disease type B in pregnancy.

PMID- 9166355
TI  - Fetal atrial flutter associated with maternal beta-sympathomimetic drug exposure.

PMID- 9166356
TI  - Laparoscopic treatment of intraligamentous pregnancy.

PMID- 9166357
TI  - Haemophilus influenzae salpingitis and septicemia in an adult.

PMID- 9166358
TI  - Intraperitoneal spread of cervical carcinoma after laparoscopic lymphadenectomy.

PMID- 9166359
TI  - A critical review of the relationship between gestational weight gain and preterm
      delivery.
AB  - OBJECTIVE: To review the relationship between gestational weight gain and preterm
      delivery. DATA SOURCES: We identified published studies through Medline searches
      (for the period 1980-1996), and we reviewed bibliographies from published
      articles. METHODS OF STUDY SELECTION: We excluded non-English-language articles
      and articles that used total weight gain, unadjusted for gestational age.
      Thirteen articles were identified for review. TABULATION, INTEGRATION AND
      RESULTS: Eleven of the 13 studies reported a significant association between
      maternal weight gain and risk of preterm delivery, and most reported that
      inadequate rate of maternal weight gain was associated with an increased risk
      (approximately 50-100%) of preterm delivery. Studies examining pattern of gain
      noted that a low rate of gain during the latter part of pregnancy (but not early
      pregnancy) was associated with an increased risk of preterm delivery (also
      approximately 50-100%). The studies' findings were relatively consistent, despite
      the use of diverse samples, study designs, and analytic strategies. CONCLUSION:
      The evidence suggests that a lower rate of weight gain during pregnancy is
      associated with an increased risk of preterm delivery, and that a slow rate of
      gain during the latter part of pregnancy may be particularly important. To
      improve our understanding of the mechanisms of these relationships, future
      studies should examine pattern of gain; they should stratify analyses on the
      different subtypes of preterm delivery and provide more detailed descriptions of
      methods for assessing gestational duration.

PMID- 9166360
TI  - Oxytocin and its receptor in pregnancy and parturition: current concepts and
      clinical implications.
AB  - OBJECTIVE: To present our current understanding of oxytocin and its receptors
      during pregnancy and parturition and their potential clinical applications. DATA
      SOURCES: A MEDLINE search was conducted for pertinent articles from 1966 to
      October 1996 related to oxytocin and its receptor and their clinical implications
      during pregnancy and parturition. Review articles, book chapters, and published
      trials were also searched. METHODS OF STUDY SELECTION: Only references in English
      that were deemed relevant were used. When possible, human data and sometimes
      animal data pertinent to understanding the interaction of oxytocin and its
      receptors were selected. TABULATION, INTEGRATION, AND RESULTS: Oxytocin is
      synthesized in the hypothalamus and in many reproductive tissues during
      pregnancy, whereas the receptors are synthesized in reproductive tissues. The
      genes for oxytocin and its receptors are on chromosomes 20 and 3, respectively.
      Oxytocin and its receptors are regulated by sex steroids and by oxytocin itself.
      The paracrine and autocrine mechanisms regulating oxytocin and its receptor
      within the fetoplacental-uterine unit are central to the control of uterine
      contractions and parturition. Such current understanding provides the basis for
      appropriate oxytocin regimens to induce or augment labor, to inhibit preterm
      labor by blockade of oxytocin receptors, and to achieve cervical ripening.
      CONCLUSION: Advances in our knowledge of oxytocin and its receptor have provided
      rational and sound principles for current concepts about their role in
      parturition, the appropriate use of oxytocin to stimulate the pregnant uterus or
      ripen the cervix, and the use of oxytocin antagonist to inhibit uterine
      contractions and preterm labor.

PMID- 9166361
TI  - Hepatitis C in pregnancy.
AB  - OBJECTIVE: To review the epidemiology and clinical course of hepatitis C virus
      (HCV) infection, to examine current data on the vertical transmission of HCV to
      neonates, and to develop recommendations for intrapartum and postpartum follow-up
      of neonates born to HCV-infected mothers. DATA SOURCES: The English-language
      medical literature from 1988 to 1996 was reviewed through MEDLINE. METHODS OF
      STUDY SELECTION: Case series evaluating vertical transmission of HCV infection in
      neonates, determined by HCV RNA testing, after delivery and breast-feeding were
      reviewed and summarized. TABULATION, INTEGRATION, AND RESULTS: Vertical
      transmission of HCV infection was examined with respect to maternal human
      immunodeficiency virus (HIV) status (as heterosexual transmission of HCV is
      enhanced in HIV-positive patients) and chronicity of HCV infection. Vertical
      transmission of HCV from HIV-negative mothers with chronic hepatitis C ranged
      from 0 to 18%. The risk of HCV vertical transmission from HIV-negative mothers
      with acute hepatitis C may be higher than that from mothers with chronic HCV
      infection. Vertical transmission of HCV was proportional to maternal HCV RNA
      levels; no transmission was noted in women without HCV RNA, whereas the greatest
      transmission was noted in women with HCV RNA greater than 1 million copies/mL.
      Vertical transmission of HCV from HIV-positive mothers with chronic hepatitis C
      ranged from 6 to 36%. In colostrum, HCV RNA was found to be present in low
      titers. No studies have documented transmission of HCV infection to infants via
      breast-feeding. CONCLUSION: Vertical transmission of HCV complicates up to 18% of
      pregnancies in HCV-positive, HIV-negative women and 6-36% in HCV-positive, HIV
      positive women. The highest rates of vertical transmission of HCV were noted in
      women with high HCV RNA or concurrent HIV infection. Breast-feeding has not been
      associated with vertical transmission of HCV infection.

PMID- 9166362
TI  - Stress echocardiography: introduction, history, and methods.
AB  - This symposium focuses on the basic and advanced methodology of stress
      echocardiography and outlines its applications and clinical impact as they relate
      to the evaluation of patients in a contemporary cardiology practice. This section
      deals with the history of the technique, the theory behind its development, and
      the methodology of the various stress echocardiography techniques. Subsequent
      sections will deal with its accuracy for identifying coronary artery disease in
      patients with chest pain syndromes, its utility as a prognostic tool, its use in
      patients with valvular disease, pulmonary hypertension, and other noncoronary
      syndromes, and finally, new uses such as the evaluation of myocardial viability.

PMID- 9166363
TI  - Stress echocardiography in the evaluation of chest pain and accuracy in the
      diagnosis of coronary artery disease.
AB  - Stress echocardiography has emerged as a valuable technique for the noninvasive
      detection of coronary artery disease. The accuracy of exercise echocardiography,
      using treadmill or bicycle stress, and of pharmacological stress
      echocardiography, using dobutamine or vasodilators, has been verified in large
      numbers of patients. In the detection of coronary artery disease, its accuracy is
      superior to that of the exercise electrocardiogram and appears comparable to the
      accuracy of SPECT perfusion imaging. In addition, stress echocardiography is
      useful in the localization and quantitation of coronary artery disease. Unique to
      stress echocardiography is the potential to detect other forms of heart disease
      that may be associated with chest pain. These characteristics support its use in
      the evaluation of the patient with chest pain.

PMID- 9166364
TI  - Prognostic issues in stress echocardiography.
AB  - Previous investigations confirm the accuracy of stress echocardiography for the
      diagnosis of coronary artery disease in patients who present with chest pain
      syndromes, in patients undergoing coronary interventions, and in patients before
      noncardiac surgery. The use of stress echo to determine prognosis is less well
      investigated. Several recent studies have been published utilizing which use
      stress echocardiographic techniques to evaluate prognosis in the general
      population of those referred for echocardiographic stress testing. These show the
      ability of both exercise and pharmacologic stress echo to stratify a referral
      population into subsets of low, high, and intermediate risk. Further studies are
      needed to determine whether these initial observations are validated on longer
      follow-up and whether stress echocardiography will play a role in therapeutic
      management through assessment of outcomes.

PMID- 9166365
TI  - Stress echocardiography for evaluation of hemodynamics: valvular heart disease,
      prosthetic valve function, and pulmonary hypertension.
AB  - A broad variety of diseases can affect dynamic cardiac function and contribute to
      exertional symptoms. Although hemodynamic data at rest may be sufficient to guide
      therapy in some patients with cardiovascular disease, medical and surgical
      decisions may be impacted by the cardiac response to stress and the ability to
      associate exertional symptoms with cardiac hemodynamic response. Stress
      echocardiography/ Doppler provides a unique noninvasive means to evaluate
      cardiovascular function and ehmodynamic responses during increased cardiac work.
      Specifically, stress echocardiographic/Doppler imaging allows assessment of the
      response to exercise of left and right ventricular function, transvalvular and
      prosthetic valve gradients, and right ventricular systolic pressure. It has
      substantial clinical use in the evaluation of patients with equivocal evidence of
      mitral stenosis, suspicion of dynamic mitral insufficiency or prosthetic valve
      dysfunction, aortic stenosis and impaired left ventricular systolic function,
      diseases associated with pulmonary hypertension or cor pulmonale, and among
      patients with dyspnea of unknown origin. The dynamic nature of cardiovascular
      disease and the broad spectrum of diseases that affect cardiac function make
      exercise echocardiography/Doppler an ideal tool ideal for the noninvasive
      assessment of patients with symptoms of exertional dyspnea.

PMID- 9166366
TI  - Evaluation of myocardial viability using stress echocardiography.
AB  - Stress echocardiography is a commonly employed technique for the diagnosis of
      coronary artery disease and for determining patient prognosis. More recently, it
      has been shown to be a valuable tool for determining myocardial viability in both
      acute and chronic ischemic coronary syndromes. The response of myocardial
      segments that are dysfunctional at rest to low dose stimulation with dobutamine
      predicts eventual recovery of function with a level of accuracy equivalent to
      that of the competing radionuclide techniques. Identification of patients with
      significant areas of viable myocardium plays a valuable role in decision making
      for high risk intervention and multivessel bypass surgery. Additionally,
      identification of viable myocardial carries significant prognostic implications
      for future cardiac events.

PMID- 9166367
TI  - Mitral valve reconstruction for mitral insufficiency.
AB  - Mitral valve reconstruction is now the procedure of choice for many mitral
      regurgitant lesions. Early enthusiasm and technical advances in plastic
      reconstruction of the mitral valve were overshadowed by the development of
      prosthetic and bioprosthetic valves. With long-term follow-up studies came the
      realization that the complication rates of prosthetic mitral valves and the
      durability of bioprostheses were less than ideal. The use of annuloplasty rings
      and standardization of mitral repair techniques have made these procedures more
      universally reliable and the excellent results reproducible. Due to the
      pathological diversity of mitral regurgitation, many different techniques are
      used to correct the various lesions. Many centers are reporting hospital
      mortality, survival, freedom from thromboembolism, freedom from reoperation,
      freedom from infective endocarditis, and freedom from valve-related complications
      results that compare favorably with those following mitral valve replacement. The
      preservation of the papillary muscles and chordae tendinea during mitral
      reconstruction, as well as a lack of foreign materials, contribute to the
      enhanced systolic function with improved survival and lower complication rates
      following mitral repair compared with replacement. With improved results and
      technical advances, the indications for mitral repair have expanded to encompass
      a broader diversity of lesions and earlier operative intervention.

PMID- 9166368
TI  - The use of inhaled nitric oxide in the acute respiratory distress syndrome.

PMID- 9166369
TI  - Septic shock: current concepts.

PMID- 9166370
TI  - Practical procedures in critical care: how to do it.

PMID- 9166371
TI  - Is Parkinson's disease inherited?
AB  - There has been considerable uncertainty as to whether idiopathic Parkinson's
      disease may be inherited except in a few rare instances. The evidence for and
      against inheritance is reviewed. The recent discovery of genetic linkage to
      chromosome 4q in a large Italian pedigree with parkinsonism has shed new light on
      this problem.

PMID- 9166372
TI  - Acute peritoneal dialysis: how to do it.
AB  - The decline in the use of acute peritoneal dialysis which has followed the recent
      advances in extracorporeal renal replacement therapy has left many clinicians
      unfamiliar with an invaluable therapeutic tool. This article is a timely reminder
      of both the underlying theory and the practical aspects of this technique.

PMID- 9166373
TI  - Multiple sclerosis: early management.
AB  - The management of multiple sclerosis (MS) is changing, and for the first time
      treatments which appear to influence the course of the disease are becoming
      available. This article examines our current understanding of MS pathogenesis and
      assesses which, if any, of the emerging therapies are likely to make an impact on
      this potentially disabling condition.

PMID- 9166374
TI  - Docetaxel.
AB  - Paclitaxel was the first taxoid to become available. It was found to be an active
      anticancer agent but with significant toxicity. Docetaxel is a semisynthetic
      taxoid and the next of a fast-expanding class of drugs. Studies suggest that
      docetaxel may be more effective and less toxic than paclitaxel.

PMID- 9166375
TI  - Preschool problems.

PMID- 9166376
TI  - Developmental disorders.

PMID- 9166377
TI  - Psychological aspects of chronic illness in children.

PMID- 9166378
TI  - MRCOG. External cephalic version.

PMID- 9166379
TI  - MRCP. Slides in dermatology: 1.

PMID- 9166381
TI  - Undervalued resources: the professions allied to medicine.
AB  - The therapy professions are a poorly understood or recognized resource for
      health, education and social care. This looks at some of the skills developed by
      these professions in response to their small numbers and relatively low status
      that could be harnessed and utilized.

PMID- 9166380
TI  - Non-surgical treatment of variceal haemorrhage.
AB  - Bleeding from gastro-oesophageal varices is a serious medical emergency
      associated with high morbidity and mortality. Recent advances in treatment
      include the use of safer vasoactive agents, endoscopic injection of
      cyanoacrylate, endoscopic variceal ligation and radiological porto-systemic
      shunt. This article will discuss these new therapies and suggest an integrated
      approach to the management of variceal haemorrhage.

PMID- 9166382
TI  - Complications of resuscitation: mediastinal blood transfusion.

PMID- 9166383
TI  - Polymerase chain reaction.

PMID- 9166384
TI  - Treatment of hyperkalaemia.

PMID- 9166385
TI  - Treatment-resistant affective disorders.

PMID- 9166386
TI  - Polycystic ovary syndrome.

PMID- 9166387
TI  - The epidemiology of quantitative ultrasound: a review of the relationships with
      bone mass, osteoporosis and fracture risk.
AB  - Quantitative ultrasound (QUS) is a simple, inexpensive and non-invasive measure
      of bone which has been used in research settings for the prediction of
      osteoporosis. This review summarizes the current status of the epidemiology of
      QUS analysis, including its relationship with bone mineral density (BMD), risk of
      osteoporotic fracture and risk factors for osteoporosis. Although only moderately
      correlated with BMD, QUS appears to be as strong a predictor of osteoporotic
      fracture as BMD and may predict fracture independent of BMD. Risk factors for low
      QUS, including age, menopause, body composition and physical inactivity, seem to
      parallel those of low BMD. More longitudinal research is needed to confirm the
      clinical utility of QUS and more experimental and population-based studies are
      needed to determine whether the etiology of low QUS values is different from that
      of low bone mass.

PMID- 9166388
TI  - Calcaneal ultrasound attenuation in older African-American and Caucasian-American
      women.
AB  - The lower fracture rates among African-American women relative to Caucasian women
      may reflect their higher bone mass. However, bone mass is not the only
      determinant of bone strength: the quality and microarchitecture of the bone are
      also important. Quantitative ultrasound is believed to measure properties of bone
      strength that are independent of bone mass. To test the hypothesis that there are
      racial differences in quantitative ultrasound measures of bone, we recruited 154
      African-American women age > or = 65 years. A random sample of 300 Caucasian
      women participating in the Study of Osteoporotic Fractures in Pittsburgh,
      Pennsylvania, was chosen for comparison. The Walker Sonix UBA 575+ was used to
      measure calcaneal broadband ultrasonic attenuation (BUA). Duplicate BUA
      measurements were obtained with a reproducibility of 5%. We measured bone mineral
      density (BMD) of the hip and calcaneus using single (calcaneus) or dual (hip)
      energy X-ray absorptiometry. The correlation between BUA and calcaneal BMD was
      similar in Caucasians (r = 0.66, p < 0.001) and African-Americans (r = 0.58, p <
      0.001). Age-adjusted BUA (dB/MHz) was higher among the African-American women
      than Caucasian women (69.1 and 66.2, respectively), but these differences were
      not statistically significant, (p = 0.12). Adjustment for calcaneal BMD
      completely attenuated the racial differences in BUA. BMD at the femoral neck and
      calcaneus was higher among the African-American women, even after adjusting for
      age, height and weight. In conclusion, our results suggest that racial
      differences in rates of fracture cannot be explained by differences in bone
      quality as assessed by ultrasound attenuation.

PMID- 9166389
TI  - Differences in mineral homeostasis, volumetric bone mass and femoral neck axis
      length in black and white South African women.
AB  - In South Africa, appendicular and lumbar spine bone mineral density (BMD) have
      been found to be similar in black and white women. However, femoral BMD has been
      found to be higher in black than in white women. Two different techniques were
      used to recalculate BMD to eliminate the possible confounding influence of ethnic
      differences in height on areal BMD measurements. Volumetric bone mineral apparent
      density (BMAD) values were calculated and bone mineral content (BMC) was
      corrected for body and bone size. This report analyses differences in BMD
      (corrected for height and weight), BMAD, BMC (corrected for body and bone size),
      femoral neck axis length (FNAL), mineral homeostasis and bone turnover (BT) in a
      group of 20 to 49-year-old premenopausal (105 whites and 74 blacks) and 45 to 64
      year-old postmenopausal (50 whites and 65 blacks) female South African nurses.
      The corrected BMD and BMC findings were congruous, showing that both pre- and
      postmenopausal blacks and whites have similar distal radius and lumbar spine bone
      mass but that whites have lower femoral neck bone mass than blacks. In contrast,
      BMAD findings suggest that pre- and postmenopausal whites have lower bone mass at
      the lumbar spine and femoral neck than blacks but similar bone mass at the distal
      radius to blacks. There is a greater rate of decline in BMD in postmenopausal
      whites than in blacks. BMD at the femoral neck was 12.1% lower in premenopausal
      whites and 16.5% lower in postmenopausal whites than in blacks. There was a
      positive association between femoral neck BMD and weight in premenopausal blacks
      (R2 = 0.5, p = 0.0001) but not in whites. Blacks had shorter FNAL than whites in
      both the pre- and post-menopausal groups. Blacks had lower serum 25
      hydroxyvitamin D (25-(OH)D) and higher 1,25-dihydroxyvitamin D (1,25-(OH)2D)
      levels than whites. There were no ethnic differences in biochemical markers of
      bone formation (serum alkaline phosphatase and osteocalcin) or bone resorption
      (urine hydroxyproline and pyridinoline), or in dietary calcium intake in either
      the pre- or postmenopausal groups. In the postmenopausal group, whites had higher
      ionized serum calcium (p = 0.003), similar serum albumin, lower serum parathyroid
      hormone (p = 0.003) and higher urinary calcium excretion (p = 0.0001) than
      blacks. These results suggest that the higher peak femoral neck BMD in South
      African blacks than in whites might be determined by greater weight-bearing in
      blacks and that the significantly lower femoral neck BMD in postmenopausal whites
      than in blacks is determined by lower peak femoral neck BMD and a faster
      postmenopausal decline in BMD in whites. The higher incidence of femoral neck
      fractures in South African whites than in blacks is probably determined by the
      lower femoral neck BMD and longer FNAL in whites. The greater rate of decline in
      BMD in postmenopausal whites than in blacks is associated with an increase in
      urinary calcium excretion in whites. Measurement of biochemical markers of BT has
      not contributed to the understanding of ethnic differences in BMD and skeletal
      metabolism in our subjects.

PMID- 9166390
TI  - Age-related changes in vertebral height ratios and vertebral fracture.
AB  - Because no gold standard for the definition of vertebral fracture exists, there
      has been controversy about whether mild vertebral deformities are truly fractures
      or simply normal variation in vertebral size and shape. The aim of this study was
      to assess the associations of mild variations of vertebral height ratios to
      definite vertebral fractures. In 479 Japanese women (aged 53.9 +/- 9.1 years) who
      visited our institute for a medical checkup, we performed lateral lumbar
      radiographs and morphometric parameters were derived by measuring the anterior
      (Ha), middle (Hm) and posterior (Hp) height of each vertebral body from T12 to
      L4. Vertebral height ratios, Ha/Hp, Hm/Hp or Hp/Hp' of adjacent vertebrae that
      were more than 3 SD different from vertebra-specific means of normative data were
      considered to indicate fractures. Forty-five women were diagnosed with at least
      one fracture. After excluding the subjects with vertebral fracture, we examined
      the associations of the variations in vertebral height ratios with age,
      anthropometric parameters and lumbar bone mineral density (BMD) measured by dual
      energy X-ray absorptiometry. Vertebral height ratios, especially Hm/Hp in
      postmenopausal women, tended to decrease with age and were positively associated
      with BMD. No significant correlation was observed between anthropometric
      parameters and vertebral height ratios. Aged-related decrease in vertebral height
      ratios (Ha/Hp and Hm/Hp, each averaged from T12 to L4) was significant even after
      the correction for BMD. Mean values of height ratios of non-fractured vertebrae
      adjusted for age and BMD were significantly lower in postmenopausal women with
      vertebral fracture than in those without vertebral fracture. Logistic regression
      analysis showed that BMD and height ratios of non-fractured vertebrae were
      independent predictors of vertebral fracture risk. The results suggest that older
      women, and women with at least one obvious (3 SD) fracture, tend to have mild
      deformities which do not qualify using the 3 SD definition. These mild
      deformities may represent real consequences of osteoporosis, because they are
      more pronounced among women with obvious fracture.

PMID- 9166391
TI  - Ipriflavone prevents radial bone loss in postmenopausal women with low bone mass
      over 2 years.
AB  - Two hundred and fifty-five postmenopausal women with distal forearm bone mineral
      density (BMD) 1 SD below the mean value for normal age-matched postmenopausal
      subjects were randomly allocated to a 2-year treatment with oral ipriflavone (200
      mg t.i.d) or a matched placebo, according to a double-masked, parallel group
      design. All patients also received a 1 g/day calcium supplement. Distal radius
      BMD and bone metabolism markers were measured at baseline, and every 6 months.
      Blood haematology and chemistry and physical parameters were monitored at the
      same time. One hundred and ninety-six patients completed 2 years of treatment.
      BMD changes from baseline were analysed according to valid completers (VC) and
      intention to treat (ITT) analyses. In both cases radial BMD was maintained in
      patients treated with ipriflavone while in decrease in those receiving the
      placebo, the between-treatment difference being significant at year 1 and year 2.
      Urinary hydroxyproline/creatinine levels were decreased in the ipriflavone
      treated group and increased in the placebo group, with a significant between
      treatment difference. Adverse reactions, mainly gastrointestinal, occurred to a
      similar extent in the two treatment groups.

PMID- 9166392
TI  - Vitamin D and HRT: no benefit additional to that of HRT alone in prevention of
      bone loss in early postmenopausal women. A 2.5-year randomized placebo-controlled
      study.
AB  - The study was designed to examine the effect of hormone replacement therapy (HRT)
      and low-dose bone loss in non-osteoporotic early postmenopausal women and to
      determine whether Vit D supplementation can give additional benefit to an already
      optimized estrogen regimen. The effects of HRT and Vit D on bone mineral density
      (BMD) were studied in postmenopausal women in a 2.5-year randomized placebo
      controlled study. The study population was a subgroup of the Kuopio Osteoporosis
      Risk Factor and Prevention Study (OSTPRE) (n = 13100). A total of 464 early
      postmenopausal women were randomized to four groups: (1) HRT (a sequential
      combination of 2 mg estradiol valerate and 1 mg cyproterone acetate (E2Val/CPA);
      (2) vitamin D3 (cholecalciferol, 300 IU/day); (3) HRT + Vit D; and (4) placebo
      (calcium lactate; 93 mg Ca2+/day). Lumbar (L1-4) and femoral neck BMD were
      determined by dual-energy X-ray absorptiometry before and after 2.5 years of
      treatment. After 2.5 years, lumbar BMD had increased by 1.8% in the HRT group (p
      > 0.001) and by 1.4% in the HRT + Vit D group (p = 0.002), whereas lumbar BMD had
      decreased by 3.5% (p < 0.001) in the Vit D group and by 3.7% (p < 0.001) in the
      placebo group. The loss of femoral neck BMD was lower in the HRT (-0.3%) and the
      HRT + Vit D (0.9%) groups compared with the Vit D (-2.4%) and the placebo groups
      (-3.7%). This study confirms the beneficial effect of HRT on BMD. It also shows
      that low-dose vitamin D supplementation has only a minor effect in the prevention
      of osteoporosis in non-osteoporotic early postmenopausal women and does not give
      any benefit additional to that of HRT alone.

PMID- 9166393
TI  - Intermittent Etidronate partially prevents bone loss in hirsute hyperandrogenic
      women treated with GnRH agonist.
AB  - Treatment with gonadotropin-releasing hormone (GnRH) agonist leads to enhanced
      bone turnover and accelerated bone loss in premenopausal women with
      endometriosis, uterine leiomyomatomas and hirsutism. Sodium etidronate is a
      powerful inhibitor of bone resorption which had been proven efficacious in the
      prevention and treatment of postmenopausal osteoporosis. The objective of this
      study was to evaluate the skeletal effects of 6 months of therapy with the depot
      preparation of the GnRH agonist triptorelin (decapeptil 3.75 mg intramuscularly
      every 4 weeks) in 24 hirsute patients, aged 24-33 years, with hyperandrogenic
      chronic anovulation. Ten patients also received cyclical etidronate in an oral
      dose of 400 mg/day for 2 weeks, followed by an 11-week period of 500 mg/day
      elemental oral calcium (one cycle). The remaining 14 patients received 500 mg/day
      of elemental calcium continuously. After 6 months all treatments were
      discontinued for at least a further 6 months. Bone mineral density (BMD) at
      lumbar spine and hip (dual-energy X-ray absorptiometry, Sophos LXRA, France) and
      biochemical markers (serum alkaline phosphatase, osteocalcin, urinary N
      telopeptide and hydroxyproline/creatinine ratio) were evaluated at baseline, 6
      months and 12 months. In the group given GnRH agonist alone BMD fell
      significantly at all measured skeletal sites during the first 6 months. In the
      patients treated with etidronate a significant decrease in BMD was observed at
      lumbar spine but not in the femoral neck and trochanter, and the changes at
      lumbar spine and trochanter were significantly smaller than those in the control
      group. At 6 months bone turnover was also increased in patients treated with GnRH
      and calcium. Cyclical etidronate prevented the increase in biochemical markers of
      bone formation and resorption, with the exception of calcium/creatinine
      excretion, which was significantly increased in both groups. Six months after
      treatment withdrawal BMD did not recover in either group. Biochemical markers (N
      telopeptide, serum alkaline phosphatase) remained increased in those patients
      previously treated with calcium alone while they remained close to baseline
      values in the patients treated with cyclical etidronate. Our study indicates
      that: (1) GnRH agonist therapy causes remarkable bone loss in young individuals
      with androgen excess who are expected to have increased bone mass; (2) this bone
      loss can be partially prevented by intermittent cyclical etidronate therapy.

PMID- 9166394
TI  - The hospital burden of vertebral fracture in Europe: a study of national register
      sources.
AB  - The aims of this study were to quantify the hospital burden of vertebral fracture
      in Europe and to compare this with that of hip fracture. Information on hospital
      discharges was sought by age and sex from Ministries of Health in Europe.
      Discharge rates for vertebral fracture, available from 12 countries, varied by
      more than 4-fold between countries, which was greater than the differences
      between sexes. Where the discharge rate was high for vertebral fracture the
      incidence of hip fracture was also high. Since nearly all cases of hip fracture
      are hospitalized, this suggests a relationship between hip and vertebral fracture
      risk that is not explained by different admission policies for vertebral
      fractures European countries.

PMID- 9166395
TI  - Ex vivo estimation of thoracolumbar vertebral body compressive strength: the
      relative contributions of bone densitometry and vertebral morphometry.
AB  - The estimation of vertebral fracture risk in individuals with suspected
      osteopenia is commonly based on measurements of lumbar spine bone density. The
      efficacy of vertebral size and deformity, as assessed by vertebral morphometry,
      in the prediction of fractures has been less studied. In an ex vivo investigation
      the regional relationships between vertebral size, vertebral deformity, bone
      density and compressive strength throughout the thoracolumbar spine were
      examined. In 16 vertebral columns (T1-L5) the bone mineral content (BMC) and bone
      mineral density (BMD) of each segment were measured using lateral projection dual
      energy X-ray absorptiometry, and the vertebral cancellous density (VCD) and mid
      vertebral cross-sectional area (CSA) measured using quantitative computed
      tomography. Vertebral body heights were determined from mid-sagittal CT scans,
      and vertical height ratios calculated for each segment. The failure load and
      failure stress of the isolated vertebral bodies were determined using a material
      testing device. Separate analyses were performed for the upper (T1-4), middle (T5
      8) and lower (T9-12) thoracic, and lumbar (L1-5) segments. In all regions,
      failure load was strongly correlated with BMD (r = 0.82-0.86), moderately
      correlated with VCD (r = 0.60-0.71) and vertebral height (r = 0.22-0.49), and
      poorly correlated with the height ratios (r = 0.04-0.33). Failure stress was best
      predicted by BMD (r = 0.73-0.78) and VCD (r = 0.70-0.78) but was poorly
      correlated with all morphometric variables (r = 0.01-0.33). The segmental
      correlations between BMD and VCD ranged form r = 0.49 to r = 0.79. For all
      regions, BMD and VCD were included in the stepwise regression models for
      predicting failure load and failure stress. Either the mid-vertebral height or
      CSA were included in all the failure load models, while mid-vertebral height was
      included in only one of the failure stress models. The results suggest that
      vertebral deformity and size (as assessed by vertebral morphometry) make only a
      minor contribution to the prediction of vertebral strength additional to that
      provided by bone densitometry alone. The consistent regional relationships
      between variables appear to support the practice of global fracture risk
      assessment based on lumbar spine densitometry.

PMID- 9166396
TI  - The number and incidence of minor trauma knee fractures are increasing in elderly
      women but not in elderly men.
AB  - To improve knowledge of the current trends in the number and incidence of age
      related minor trauma knee fractures, we selected from the National Hospital
      Discharge Register all patients 60 years old or older who were admitted to
      Finnish hospitals in 1970-1972, 1974-1975, 1978-1980, 1983-1985, 1988-1989 and
      1991-1994 for primary treatment of first knee fracture. The knee fracture was
      defined to be a "minor trauma" fracture if it had occurred as a result of a fall
      from standing height or less. We also predicted fracture development until the
      year 2020 by a regression model, which took into account the predicted changes in
      fracture incidences and population at risk. The number and incidence (per 100,000
      persons) of minor trauma knee fractures in Finnish women aged 60 years or more
      clearly increased during the study period, from 219 (number) and 55 (incidence)
      in 1970 to 579 and 100 in 1994. Women's age-adjusted incidence of these fractures
      also showed an increase, from 58/100,000 in 1970 to 93/100,000 in 1994. If this
      trend continues, there will be about 2 times more minor trauma knee fractures in
      Finnish women in the year 2020 than there were in 1994. In Finnish men aged 60
      years or more the absolute numbers and incidences of these fractures did not show
      consistent trend changes over time. We conclude that the number of minor trauma
      knee fractures in elderly Finnish women in increasing more rapidly than can be
      accounted for by the demographic changes alone and therefore effective preventive
      measures should urgently be adopted to control the increasing burden of these age
      related fractures.

PMID- 9166397
TI  - A high dietary calcium intake is needed for a positive effect on bone density in
      Swedish postmenopausal women.
AB  - The importance of dietary calcium for bone health is unclear, partly since most
      investigations have dealt only with a fairly narrow range of calcium intake. In
      the present population-based observational study with longitudinal dietary
      assessment, we investigated women with a mean age of 60 years and with a
      consistently high (range 1417-2417, mean 1645 mg, n = 40), intermediate (800
      1200, mean 1006 mg, n = 35) or low (400-550, mean 465 mg, n = 40) estimated daily
      consumption of calcium. Measurements of bone mineral density (BMD) of the lumbar
      spine, femoral neck and total body were performed by dual-energy X-ray
      absorptiometry, as well as ultrasound of the heel. In a multivariate analysis,
      with adjustment for energy intake the risk factors for osteoporosis (age, body
      mass index, physical activity, menopausal age, use of estrogens, smoking and
      former athletic activity), the group with the highest calcium intake had higher
      values for BMD than the others at all measured sites. The average mean difference
      compared with the low and the intermediate calcium group was 11% for the femoral
      neck, 8-11% for the lumbar spine and 5-6% for total body BMDs. In univariate
      analyses and multivariate models which did not include energy intake, the
      differences between the groups were less pronounced. The women in the
      intermediate calcium group had approximately the same mean BMD values as those in
      the low calcium group. These findings support the view that only a high calcium
      intake (3% highest percentiles in the studied population) protects against
      osteoporosis in Swedish postmenopausal women.

PMID- 9166398
TI  - Initiation of hormone replacement therapy after diagnosis of osteoporosis by bone
      densitometry.
AB  - The effect of osteoporosis, as diagnosed by bone densitometry, on general
      practitioners' decisions to initiate hormone replacement therapy (HRT) was
      assessed. Data for the study were collected by questionnaire from 147 women (> 40
      years), previously referred for measurement of bone mineral density (BMD) at the
      proximal forearm. Among the women, at the time of BMD measurement, current and
      ever use of HRT was 35% and 50% respectively, and 25.2% were osteoporotic on the
      basis of their BMD level. HRT was more likely to be initiated by women who were
      told that their BMD was low (ODR 3.4; 95% CI 1.2-9.7); 37% of all women with
      osteoporosis were using HRT compared with 78% who were taking calcium
      supplements. Potential reasons for the low HRT prescription may include the
      nature of the BMD report, patient aversion to HRT and doctors' concern with the
      long-term side-effects of HRT.

PMID- 9166399
TI  - The dynamic organization of the perinucleolar compartment in the cell nucleus.
AB  - The perinucleolar compartment (PNC) is a unique nuclear structure preferentially
      localized at the periphery of the nucleolus. Several small RNAs transcribed by
      RNA polymerase III (e.g., the Y RNAs, MRP RNA, and RNase P H1 RNA) and the
      polypyrimidine tract binding protein (PTB; hnRNP I) have thus far been identified
      in the PNC (Ghetti, A., S. PinolRoma, W.M. Michael, C. Morandi, and G. Dreyfuss.
      1992. Nucleic Acids Res. 20:3671-3678; Matera, A.G., M.R. Frey, K. Margelot, and
      S.L. Wolin. 1995. J. Cell Biol. 129:1181-1193; Lee, B., A.G. Matera, D.C. Ward,
      and J. Craft. 1996. Proc. Natl. Acad. Sci. USA. 93: 11471-11476). In this report,
      we have further characterized this structure in both fixed and living cells.
      Detection of the PNC in a large number of human cancer and normal cells showed
      that PNCs are much more prevalent in cancer cells. Analysis through the cell
      cycle using immunolabeling with a monoclonal antibody, SH54, specifically
      recognizing PTB, demonstrated that the PNC dissociates at the beginning of
      mitosis and reforms at late telophase in the daughter nuclei. To visualize the
      PNC in living cells, a fusion protein between PTB and green fluorescent protein
      (GFP) was generated. Time lapse studies revealed that the size and shape of the
      PNC is dynamic over time. In addition, electron microscopic examination in
      optimally fixed cells revealed that the PNC is composed of multiple strands, each
      measuring approximately 80-180 nm diam. Some of the strands are in direct contact
      with the surface of the nucleolus. Furthermore, analysis of the sequence
      requirement for targeting PTB to the PNC using a series of deletion mutants of
      the GFP-PTB fusion protein showed that at least three RRMs at either the COOH or
      NH2 terminus are required for the fusion protein to be targeted to the PNC. This
      finding suggests that RNA binding may be necessary for PTB to be localized in the
      PNC.

PMID- 9166400
TI  - Targeting of U2AF65 to sites of active splicing in the nucleus.
AB  - U2AF65 is an essential splicing factor that promotes binding of U2 small nuclear
      (sn)RNP at the pre-mRNA branchpoint. Here we describe a novel monoclonal antibody
      that reacts specifically with U2AF65. Using this antibody, we show that U2AF65 is
      diffusely distributed in the nucleoplasm with additional concentration in nuclear
      speckles, which represent subnuclear compartments enriched in splicing snRNPs and
      other splicing factors. Furthermore, transient expression assays using epitope
      tagged deletion mutants of U2AF65 indicate that targeting of the protein to
      nuclear speckles is not affected by removing either the RNA binding domain, the
      RS domain, or the region required for interaction with U2AF35. The association of
      U2AF65 with speckles persists during mitosis, when transcription and splicing are
      downregulated. Moreover, U2AF65 is localized to nuclear speckles in early G1
      cells that were treated with transcription inhibitors during mitosis, suggesting
      that the localization of U2AF65 in speckles is independent of the presence of pre
      mRNA in the nucleus, which is consistent with the idea that speckles represent
      storage sites for inactive splicing factors. After adenovirus infection, U2AF65
      redistributes from the speckles and is prefferentially detected at sites of viral
      transcription. By combining adenoviral infection with transient expression of
      deletion mutants, we show a specific requirement of the RS domain for recruitment
      of U2AF65 to sites of active splicing in the nucleus. This suggests that
      interactions involving the RS region of U2AF65 may play an important role in
      targeting this protein to spliceosomes in vivo.

PMID- 9166401
TI  - Nup84, a novel nucleoporin that is associated with CAN/Nup214 on the cytoplasmic
      face of the nuclear pore complex.
AB  - The short filaments extending from the cytoplasmic face of nuclear pore complexes
      are thought to contain docking sites for nuclear import substrates. One component
      of these filaments is the large O-linked glycoprotein CAN/Nup214.
      Immunoprecipitation studies carried out under nondenaturing conditions, and using
      a variety of antibodies, reveal a novel nonglycosylated nucleoporin, Nup84, that
      is tightly associated with CAN/Nup214. Consistent with such an association, Nup84
      is found to be exposed on the cytoplasmic face of the nuclear pore complex. cDNA
      sequence analyses indicate that Nup84 contains neither the GLFG nor the XFXFG
      repeats that are a characteristic of a number of other nuclear pore complex
      proteins. Secondary structure predictions, however, suggest that Nup84 contains a
      coiled-coil COOH-terminal domain, a conclusion supported by the observation of
      significant sequence similarity between this region of the molecule and various
      members of the tropomyosin family. Mutagenesis and expression studies indicate
      that the putative coiled-coil domain is required for association with the
      cytoplasmic face of the nuclear pore complex, whereas it is the NH2-terminal
      region of Nup84 that contains the site of interaction with CAN/Nup214. These
      findings suggest a model in which Nup84 may function in the attachment of
      CAN/Nup214 to the central framework of the nuclear pore complex. In this way,
      Nup84 could play a central role in the organization of the interface between the
      pore complex and the cytoplasm.

PMID- 9166402
TI  - Insertional mutation of the Drosophila nuclear lamin Dm0 gene results in
      defective nuclear envelopes, clustering of nuclear pore complexes, and
      accumulation of annulate lamellae.
AB  - Nuclear lamins are thought to play an important role in disassembly and
      reassembly of the nucleus during mitosis. Here, we describe a Drosophila lamin
      Dm0 mutant resulting from a P element insertion into the first intron of the Dm0
      gene. Homozygous mutant animals showed a severe phenotype including retardation
      in development, reduced viability, sterility, and impaired locomotion.
      Immunocytochemical and ultrastructural analysis revealed that reduced lamin Dm0
      expression caused an enrichment of nuclear pore complexes in cytoplasmic annulate
      lamellae and in nuclear envelope clusters. In several cells, particularly the
      densely packed somata of the central nervous system, defective nuclear envelopes
      were observed in addition. All aspects of the mutant phenotype were rescued upon
      P element-mediated germline transformation with a lamin Dm0 transgene. These data
      constitute the first genetic proof that lamins are essential for the structural
      organization of the cell nucleus.

PMID- 9166405
TI  - Structural features of membrane fusion between influenza virus and liposome as
      revealed by quick-freezing electron microscopy.
AB  - The structure of membrane fusion intermediates between the A/PR/8(H1N1) strain of
      influenza virus and a liposome composed of egg phosphatidylcholine, cholesterol,
      and glycophorin was studied using quick-freezing electron microscopy. Fusion by
      viral hemagglutinin protein was induced at pH 5.0 and 23 degrees C. After a 19-s
      incubation under these conditions, small protrusions with a diameter of 10-20 nm
      were found on the fractured convex faces of the liposomal membranes, and small
      pits complementary to the protrusions were found on the concave faces. The
      protrusions and pits corresponded to fractured parts of outward bendings of the
      lipid bilayer or "microprotrusions of the lipid bilayer." At the loci of the
      protrusions and pits, liposomal membranes had local contacts with viral
      membranes. In many cases both the protrusions and the pits were aligned in
      regular polygonal arrangements, which were thought to reflect the array of
      hemagglutinin spikes on the viral surface. These structures were induced only
      when the medium was acidic with the virus present. Based on these observations,
      it was concluded that the microprotrusions of the lipid bilayer are induced by
      hemagglutinin protein. Furthermore, morphological evidence for the formation of
      the "initial fusion pore" at the microprotrusion was obtained. The protrusion on
      the convex face sometimes had a tiny hole with a diameter of <4 nm in the center.
      The pits transformed into narrow membrane connections <10 nm in width, bridging
      viruses and liposomes. The structures of the fusion pore and fusion neck with
      larger sizes were also observed, indicating growth of the protrusions and pits to
      distinct fusion sites. We propose that the microprotrusion of the lipid bilayer
      is a fusion intermediate induced by hemagglutinin protein, and suggest that the
      extraordinarily high curvature of this membrane structure is a clue to the onset
      of fusion. The possible architecture of the fusion intermediate is discussed with
      regard to the localization of intramembrane particles at the microprotrusion.

PMID- 9166403
TI  - ERS-24, a mammalian v-SNARE implicated in vesicle traffic between the ER and the
      Golgi.
AB  - We report the identification and characterization of ERS-24 (Endoplasmic
      Reticulum SNARE of 24 kD), a new mammalian v-SNARE implicated in vesicular
      transport between the ER and the Golgi. ERS24 is incorporated into 20S docking
      and fusion particles and disassembles from this complex in an ATP-dependent
      manner. ERS-24 has significant sequence homology to Sec22p, a v-SNARE in
      Saccharomyces cerevisiae required for transport between the ER and the Golgi. ERS
      24 is localized to the ER and to the Golgi, and it is enriched in transport
      vesicles associated with these organelles.

PMID- 9166404
TI  - Intrinsic signals in the unique domain target p56(lck) to the plasma membrane
      independently of CD4.
AB  - In T lymphocytes, the Src-family protein tyrosine kinase p56(lck) (Lck) is mostly
      associated with the cytoplasmic face of the plasma membrane. To determine how
      this distribution is achieved, we analyzed the location of Lck in lymphoid and in
      transfected nonlymphoid cells by immunofluorescence. We found that in T cells Lck
      was targeted correctly, independently of the cell surface proteins CD4 and CD8
      with which it interacts. Similarly, in transfected NIH-3T3 fibroblasts, Lck was
      localized at the plasma membrane, indicating that T cell-specific proteins are
      not required for targeting. Some variation in subcellular distribution was
      observed when Lck was expressed in HeLa and MDCK cells. In these cells, Lck
      associated with both the plasma membrane and the Golgi apparatus, while
      subsequent expression of CD4 resulted in the loss of Golgi-associated staining.
      Together, these data indicate that Lck contains intrinsic signals for targeting
      to the plasma membrane. Furthermore, delivery to this site may be achieved via
      association with exocytic transport vesicles. A mutant Lck molecule in which the
      palmitoylation site at cysteine 5 was changed to lysine (LC2) localized to the
      plasma membrane and the Golgi region in NIH3T3 cells. However, the localization
      of a mutant in which the palmitoylation site at cysteine 3 was changed to serine
      (LC1) was indistinguishable from wild-type Lck. Chimeras composed of only the
      unique domain of Lck linked to either c-Src or the green fluorescent protein
      similarly localized to the plasma membrane of NIH-3T3 cells. Thus, the targeting
      of Lck appears to be determined primarily by its unique domain and may be
      influenced by the use of different palmitoylation sites.

PMID- 9166406
TI  - A natural hepatocyte growth factor/scatter factor autocrine loop in myoblast
      cells and the effect of the constitutive Met kinase activation on myogenic
      differentiation.
AB  - As a rule, hepatocyte growth factor/scatter factor (HGF/SF) is produced by
      mesenchymal cells, while its receptor, the tyrosine kinase encoded by the met
      proto-oncogene, is expressed by the neighboring epithelial cells in a canonical
      paracrine fashion. In the present work we show that both HGF/SF and met are
      coexpressed by undifferentiated C2 mouse myoblasts. In growing cells, the
      autocrine loop is active as the receptor exhibits a constitutive phosphorylation
      on tyrosine that can be abrogated by exogenously added anti-HGF/SF neutralizing
      antibodies. The transcription of HGF/SF and met genes is downregulated when
      myoblasts stop proliferating and differentiate. The coexpression of HGF/SF and
      met genes is not exclusive to C2 cells since it has been assessed also in other
      myogenic cell lines and in mouse primary satellite cells, suggesting that HGF/SF
      could play a role in muscle development through an autocrine way. To analyze the
      biological effects of HGF/SF receptor activation, we stably expressed the
      constitutively activated receptor catalytic domain (p65(tpr-met)) in C2 cells.
      This active kinase determined profound changes in cell shape and inhibited
      myogenesis at both morphological and biochemical levels. Notably, a complete
      absence of muscle regulatory markers such as MyoD and myogenin was observed in
      p65(tpr-met) highly expressing C2 clones. We also studied the effects of the
      ectopic expression of human isoforms of met receptor (h-met) and of HGF/SF (h
      HGF/SF) in stable transfected C2 cells. Single constitutive expression of h-met
      or h-HGF/SF does not alter substantially the growth and differentiation
      properties of the myoblast cells, probably because of a species-specific ligand
      receptor interaction. A C2 clone expressing simultaneously both h-met and h
      HGF/SF is able to grow in soft agar and shows a decrease in myogenic potential
      comparable to that promoted by p65(tpr-met) kinase. These data indicate that a
      met kinase signal released from differentiation-dependent control provides a
      negative stimulus for the onset of myogenic differentiation.

PMID- 9166407
TI  - The Chlamydomonas reinhardtii ODA3 gene encodes a protein of the outer dynein arm
      docking complex.
AB  - We have used an insertional mutagenesis/ gene tagging technique to generate new
      Chlamydomonas reinhardtii mutants that are defective in assembly of the uter
      ynein rm. Among 39 insertional oda mutants characterized, two are alleles of the
      previously uncloned ODA3 gene, one is an allele of the uncloned ODA10 gene, and
      one represents a novel ODA gene (termed ODA12). ODA3 is of particular interest
      because it is essential for assembly of both the outer dynein arm and the outer
      dynein arm docking complex (ODA-DC) onto flagellar doublet microtubules (Takada,
      S., and R. Kamiya. 1994. J. Cell Biol. 126:737- 745). Beginning with the inserted
      DNA as a tag, the ODA3 gene and a full-length cDNA were cloned. The cloned gene
      rescues the phenotype of oda3 mutants. The cDNA sequence predicts a novel 83. 4
      kD protein with extensive coiled-coil domains. The ODA-DC contains three
      polypeptides; direct amino acid sequencing indicates that the largest of these
      polypeptides corresponds to ODA3. This protein is likely to have an important
      role in the precise positioning of the outer dynein arms on the flagellar
      axoneme.

PMID- 9166408
TI  - A Chlamydomonas homologue of the putative murine t complex distorter Tctex-2 is
      an outer arm dynein light chain.
AB  - Molecular analysis of a 19,000-Mr protein from the Chlamydomonas flagellum
      reveals that it is homologous to the t complex-encoded protein Tctex-2, which is
      a candidate for one of the distorter products that cause the extreme transmission
      ratio distortion (meiotic drive) of the murine t complex. The 19,000-Mr protein
      is extracted from the axoneme with 0.6 M NaCl and comigrates with the outer
      dynein arm in sucrose density gradients. This protein also is specifically
      missing in axonemes prepared from a mutant that does not assemble the outer arm.
      These data raise the possibility that Tctex-2 is a sperm flagellar dynein
      component. Combined with the recent identification of Tctex-1 (another distorter
      candidate) as a light chain of cytoplasmic dynein, these results lead to a
      biochemical model for how differential defects in spermiogenesis that result in
      the phenomenon of meiotic drive might be generated in wild-type vs t-bearing
      sperm.

PMID- 9166409
TI  - Targeted disruption of the pemphigus vulgaris antigen (desmoglein 3) gene in mice
      causes loss of keratinocyte cell adhesion with a phenotype similar to pemphigus
      vulgaris.
AB  - In patients with pemphigus vulgaris (PV), autoantibodies against desmoglein 3
      (Dsg3) cause loss of cell-cell adhesion of keratinocytes in the basal and
      immediate suprabasal layers of stratified squamous epithelia. The pathology, at
      least partially, may depend on protease release from keratinocytes, but might
      also result from antibodies interfering with an adhesion function of Dsg3.
      However, a direct role of desmogleins in cell adhesion has not been shown. To
      test whether Dsg3 mediates adhesion, we genetically engineered mice with a
      targeted disruption of the DSG3 gene. DSG3 -/- mice had no DSG3 mRNA by RNase
      protection assay and no Dsg3 protein by immunofluorescence (IF) and immunoblots.
      These mice were normal at birth, but by 8-10 d weighed less than DSG3 +/- or +/+
      littermates, and at around day 18 were grossly runted. We speculated that oral
      lesions (typical in PV patients) might be inhibiting food intake, causing this
      runting. Indeed, oropharyngeal biopsies showed erosions with histology typical of
      PV, including suprabasilar acantholysis and "tombstoning" of basal cells. EM
      showed separation of desmosomes. Traumatized skin also had crusting and
      suprabasilar acantholysis. Runted mice showed hair loss at weaning. The runting
      and hair loss phenotype of DSG3 -/- mice is identical to that of a previously
      reported mouse mutant, balding (bal). Breeding indicated that bal is coallelic
      with the targeted mutation. We also showed that bal mice lack Dsg3 by IF, have
      typical PV oral lesions, and have a DSG3 gene mutation. These results demonstrate
      the critical importance of Dsg3 for adhesion in deep stratified squamous
      epithelia and suggest that pemphigus autoantibodies might interfere directly with
      such a function.

PMID- 9166411
TI  - Temporal phases in apoptosis defined by the actions of Src homology 2 domains,
      ceramide, Bcl-2, interleukin-1beta converting enzyme family proteases, and a
      dense membrane fraction.
AB  - We have begun to explore the mechanisms of apoptosis using a cell-free system
      based on extracts from Xenopus eggs. Nuclei assembled or placed in these extracts
      undergo the morphological changes typical of apoptosis and eventually
      disintegrate. We used this system to investigate the potential involvement in
      apoptosis of proteins containing Src homology 2 (SH2) domains, which are known to
      interact with specific tyrosine-phosphorylated ligands. SH2 domains from a number
      of signaling proteins, including Lck, Src, and Abl, inhibited apoptosis when
      present at concentrations of 10-100 nM. The inhibition was dependent on specific
      interaction with endogenous tyrosine-phosphorylated ligands. A synthetic peptide
      ligand for Src family SH2 domains also inhibited apoptosis in a phosphotyrosine
      dependent manner. Kinetic analysis defined three phases in the apoptotic process
      occurring in this cell-free system. SH2 domains and ceramide act throughout the
      first 60-90 min of the process (the "initiation" phase). Next, Bcl-2, interleukin
      1beta converting enzyme family(CPP32-like) proteases, and the heavy membrane
      fraction act in a period occurring approximately 90-120 min after the start of
      incubation (the "sentencing" phase). In the final phase ("execution"), the
      process of active nuclear destruction ensues.

PMID- 9166410
TI  - Protein kinase C activation upregulates intercellular adhesion of alpha-catenin
      negative human colon cancer cell variants via induction of desmosomes.
AB  - The alpha-catenin molecule links E-cadherin/ beta-catenin or E
      cadherin/plakoglobin complexes to the actin cytoskeleton. We studied several
      invasive human colon carcinoma cell lines lacking alpha-catenin. They showed a
      solitary and rounded morphotype that correlated with increased invasiveness.
      These round cell variants acquired a more normal epithelial phenotype upon
      transfection with an alpha-catenin expression plasmid, but also upon treatment
      with the protein kinase C (PKC) activator 12-O-tetradecanoyl-phorbol-13-acetate
      (TPA). Video registrations showed that the cells started to establish elaborated
      intercellular junctions within 30 min after addition of TPA. Interestingly, this
      normalizing TPA effect was not associated with alpha-catenin induction. Classical
      and confocal immunofluorescence showed only minor TPA-induced changes in E
      cadherin staining. In contrast, desmosomal and tight junctional proteins were
      dramatically rearranged, with a conversion from cytoplasmic clusters to obvious
      concentration at cell-cell contacts and exposition at the exterior cell surface.
      Electron microscopical observations revealed the TPA-induced appearance of
      typical desmosomal plaques. TPA-restored cell-cell adhesion was E-cadherin
      dependent as demonstrated by a blocking antibody in a cell aggregation assay.
      Addition of an antibody against the extracellular part of desmoglein-2 blocked
      the TPA effect, too. Remarkably, the combination of anti-E-cadherin and anti
      desmoglein antibodies synergistically inhibited the TPA effect. Our studies show
      that it is possible to bypass the need for normal alpha-catenin expression to
      establish tight intercellular adhesion by epithelial cells. Apparently, the
      underlying mechanism comprises upregulation of desmosomes and tight junctions by
      activation of the PKC signaling pathway, whereas E-cadherin remains essential for
      basic cell-cell adhesion, even in the absence of alpha-catenin.

PMID- 9166412
TI  - Phosphatidylinositol 3-kinase is a negative regulator of cellular
      differentiation.
AB  - Phosphatidylinositol 3-kinase (PI3K) has been shown to be an important mediator
      of intracellular signal transduction in mammalian cells. We show here, for the
      first time, that the blockade of PI3K activity in human fetal undifferentiated
      cells induced morphological and functional endocrine differentiation. This was
      associated with an increase in mRNA levels of insulin, glucagon, and
      somatostatin, as well as an increase in the insulin protein content and secretion
      in response to secretagogues. Blockade of PI3K also increased the proportion of
      pluripotent precursor cells coexpressing multiple hormones and the total number
      of terminally differentiated cells originating from these precursor cells. We
      examined whether any of the recently described modulators of endocrine
      differentiation could participate in regulating PI3K activity in fetal islet
      cells. The activity of PI3K was inversely correlated with the hepatocyte growth
      factor/scatter factor-induced downregulation or nicotinamideinduced upregulation
      of islet-specific gene expression, giving support to the role of PI3K, as a
      negative regulator of endocrine differentiation. In conclusion, our results
      provide a mechanism for the regulation of hormone-specific gene expression during
      human fetal neogenesis. They also suggest a novel function for PI3K, as a
      negative regulator of cellular differentiation.

PMID- 9166413
TI  - An essential role for CD44 variant isoforms in epidermal Langerhans cell and
      blood dendritic cell function.
AB  - Upon antigen contact, epidermal Langerhans cells (LC) and dendritic cells (DC)
      leave peripheral organs and home to lymph nodes via the afferent lymphatic
      vessels and then assemble in the paracortical T cell zone and present antigen to
      T lymphocytes. Since splice variants of CD44 promote metastasis of certain tumors
      to lymph nodes, we explored the expression of CD44 proteins on migrating LC and
      DC. We show that upon antigen contact, LC and DC upregulate pan CD44 epitopes and
      epitopes encoded by variant exons v4, v5, v6, and v9. Antibodies against CD44
      epitopes inhibit the emigration of LC from the epidermis, prevent binding of
      activated LC and DC to the T cell zones of lymph nodes, and severely inhibit
      their capacity to induce a delayed type hypersensitivity reaction to a skin
      hapten in vivo. Our results demonstrate that CD44 splice variant expression is
      obligatory for the migration and function of LC and DC.

PMID- 9166414
TI  - Regulated production of mineralization-competent matrix vesicles in hypertrophic
      chondrocytes.
AB  - Matrix vesicles have a critical role in the initiation of mineral deposition in
      skeletal tissues, but the ways in which they exert this key function remain
      poorly understood. This issue is made even more intriguing by the fact that
      matrix vesicles are also present in nonmineralizing tissues. Thus, we tested the
      novel hypothesis that matrix vesicles produced and released by mineralizing cells
      are structurally and functionally different from those released by
      nonmineralizing cells. To test this hypothesis, we made use of cultures of chick
      embryonic hypertrophic chondrocytes in which mineralization was triggered by
      treatment with vitamin C and phosphate. Ultrastructural analysis revealed that
      both control nonmineralizing and vitamin C/phosphatetreated mineralizing
      chondrocytes produced and released matrix vesicles that exhibited similar round
      shape, smooth contour, and average size. However, unlike control vesicles, those
      produced by mineralizing chondrocytes had very strong alkaline phosphatase
      activity and contained annexin V, a membrane-associated protein known to mediate
      Ca2+ influx into matrix vesicles. Strikingly, these vesicles also formed numerous
      apatite-like crystals upon incubation with synthetic cartilage lymph, while
      control vesicles failed to do so. Northern blot and immunohistochemical analyses
      showed that the production and release of annexin V-rich matrix vesicles by
      mineralizing chondrocytes were accompanied by a marked increase in annexin V
      expression and, interestingly, were followed by increased expression of type I
      collagen. Studies on embryonic cartilages demonstrated a similar sequence of
      phenotypic changes during the mineralization process in vivo. Thus, chondrocytes
      located in the hypertrophic zone of chick embryo tibial growth plate were
      characterized by strong annexin V expression, and those located at the chondro
      osseous mineralizing border exhibited expression of both annexin V and type I
      collagen. These findings reveal that hypertrophic chondrocytes can qualitatively
      modulate their production of matrix vesicles and only when induced to initiate
      mineralization, will release mineralization-competent matrix vesicles rich in
      annexin V and alkaline phosphatase. The occurrence of type I collagen in concert
      with cartilage matrix calcification suggests that the protein may facilitate
      crystal growth after rupture of the matrix vesicle membrane; it may also offer a
      smooth transition from mineralized type II/type X collagen-rich cartilage matrix
      to type I collagen-rich bone matrix.

PMID- 9166415
TI  - Different steady state subcellular distributions of the three splice variants of
      lysosome-associated membrane protein LAMP-2 are determined largely by the COOH
      terminal amino acid residue.
AB  - The extensively glycosylated lysosome-associated membrane proteins (LAMP)-2a, b,
      and c are derived from a single gene by alternative splicing that produces
      proteins with differences in the transmembrane and cytosolic domains. The
      lysosomal targeting signals reside in the cytosolic domain of these proteins.
      LAMPs are not restricted to lysosomes but can also be found in endosomes and at
      the cell surface. We investigated the subcellular distribution of chimeras
      comprised of the lumenal domain of avian LAMP-1 and the alternatively spliced
      domains of avian LAMP-2. Chimeras with the LAMP-2c cytosolic domain showed
      predominantly lysosomal distribution, while higher levels of chimeras with the
      LAMP-2a or b cytosolic domain were present at the cell surface. The increase in
      cell surface expression was due to differences in the recognition of the
      targeting signals and not saturation of intracellular trafficking machinery. Site
      directed mutagenesis defined the COOH-terminal residue of the cytosolic tail as
      critical in governing the distributions of LAMP-2a, b, and c between
      intracellular compartments and the cell surface.

PMID- 9166416
TI  - Type IV collagen is detectable in most, but not all, basement membranes of
      Caenorhabditis elegans and assembles on tissues that do not express it.
AB  - Type IV collagen in Caenorhabditis elegans is produced by two essential genes,
      emb-9 and let-2, which encode alpha1- and alpha2-like chains, respectively. The
      distribution of EMB-9 and LET-2 chains has been characterized using chain
      specific antisera. The chains colocalize, suggesting that they may function in a
      single heterotrimeric collagen molecule. Type IV collagen is detected in all
      basement membranes except those on the pseudocoelomic face of body wall muscle
      and on the regions of the hypodermis between body wall muscle quadrants,
      indicating that there are major structural differences between some basement
      membranes in C. elegans. Using lacZ/green fluorescent protein (GFP) reporter
      constructs, both type IV collagen genes were shown to be expressed in the same
      cells, primarily body wall muscles, and some somatic cells of the gonad. Although
      the pharynx and intestine are covered with basement membranes that contain type
      IV collagen, these tissues do not express either type IV collagen gene. Using an
      epitope-tagged emb-9 construct, we show that type IV collagen made in body wall
      muscle cells can assemble into the pharyngeal, intestinal, and gonadal basement
      membranes. Additionally, we show that expression of functional type IV collagen
      only in body wall muscle cells is sufficient for C. elegans to complete
      development and be partially fertile. Since type IV collagen secreted from muscle
      cells only assembles into some of the basement membranes that it has access to,
      there must be a mechanism regulating its assembly. We propose that interaction
      with a cell surface-associated molecule(s) is required to facilitate type IV
      collagen assembly.

PMID- 9166417
TI  - Characterization of alpha1(IV) collagen mutations in Caenorhabditis elegans and
      the effects of alpha1 and alpha2(IV) mutations on type IV collagen distribution.
AB  - Type IV collagen is a major component of basement membranes. We have
      characterized 11 mutations in emb-9, the alpha1(IV) collagen gene of
      Caenorhabditis elegans, that result in a spectrum of phenotypes. Five are
      substitutions of glycines in the Gly-X-Y domain and cause semidominant,
      temperature-sensitive lethality at the twofold stage of embryogenesis. One is a
      glycine substitution that causes recessive, non-temperature-sensitive larval
      lethality. Three putative null alleles, two nonsense mutations and a deletion,
      all cause recessive, non-temperature-sensitive lethality at the threefold stage
      of embryogenesis. The less severe null phenotype indicates that glycine
      substitution containing mutant chains dominantly interfere with the function of
      other molecules. The emb-9 null mutants do not stain with anti-EMB-9 antisera and
      show intracellular accumulation of the alpha2(IV) chain, LET-2, indicating that
      LET-2 assembly and/or secretion requires EMB-9. Glycine substitutions in either
      EMB-9 or LET-2 cause intracellular accumulation of both chains. The degree of
      intracellular accumulation differs depending on the allele and temperature and
      correlates with the severity of the phenotype. Temperature sensitivity appears to
      result from reduced assembly/secretion of type IV collagen, not defective
      function in the basement membrane. Because the dominant interference of glycine
      substitution mutations is maximal when type IV collagen secretion is totally
      blocked, this interference appears to occur intracellularly, rather than in the
      basement membrane. We suggest that the nature of dominant interference caused by
      mutations in type IV collagen is different than that caused by mutations in
      fibrillar collagens.

PMID- 9166418
TI  - An isotype-specific activator of major histocompatibility complex (MHC) class II
      genes that is independent of class II transactivator.
AB  - Patients with one type of major histocompatibility complex class II combined
      immunodeficiency have mutations in a gene termed class II transactivator (CIITA),
      which coordinately controls the transcription of the three major human class II
      genes, HLA-DR, -DQ, and -DP. However, the experimentally derived B-lymphoblastoid
      cell line, clone 13, expresses high levels of HLADQ in the absence of HLA-DR and
      HLA-DP, despite its mapping by complementation analysis to this group. It was
      possible that one of the clone 13 CIITA alleles bore a mutation that allowed HLA
      DQ, but not HLA-DR or -DP transcription. Alternatively, another factor, distinct
      from CIITA, might control HLA-DQ expression. We report here that ectopic
      expression of CIITA cDNAs derived by reverse transcriptase polymerase chain
      reaction from clone 13 do not restore expression of HLA-DQ in another CIITA
      deficient cell line, RJ2.2.5. In addition, no CIITA protein is detectable in
      clone 13 nuclear extracts. In contrast, somatic cell fusion between clone 13 and
      RJ2.2.5 restored expression of the HLA-DQ haplotype encoded by the RJ2.2.5 DQB
      gene. Taken together, these data demonstrate the existence of an HLA-DQ isotype
      specific trans-acting factor, which functions independently of CIITA.

PMID- 9166419
TI  - Perturbation of the T lymphocyte lineage in transgenic mice expressing a
      constitutive repressor of nuclear factor (NF)-kappaB.
AB  - Members of the nuclear factor (NF)-kappaB/Rel family transcription factors are
      induced during thymic selection and in mature T lymphocytes after ligation of the
      T cell antigen receptor (TCR). Despite these findings, disruption of individual
      NF-kappaB/Rel genes has revealed no intrinsic defect in the development of mature
      T cells, perhaps reflecting functional redundancy. To circumvent this
      possibility, the T cell lineage was targeted to express a trans-dominant form of
      IkappaBalpha that constitutively represses the activity of multiple NF-kappaB/Rel
      proteins. Transgenic cells expressing this inhibitor exhibit a significant
      proliferative defect, which is not reversed by the addition of exogenous
      interleukin-2. Moreover, mitogenic stimulation of splenocytes leads to increased
      apoptosis of transgenic T cells as compared with controls. In addition to
      deregulated T cell growth and survival, transgene expression impairs the
      development of normal T cell populations as evidenced by diminished numbers of
      TCRhi CD8 single-positive thymocytes. This defect was significantly amplified in
      the periphery and was accompanied by a decrease in CD4(+) T cells. Taken
      together, these in vivo findings indicate that the NF-kappaB/Rel signaling
      pathway contains compensatory components that are essential for the establishment
      of normal T cell subsets.

PMID- 9166420
TI  - Human dendritic cells skew isotype switching of CD40-activated naive B cells
      towards IgA1 and IgA2.
AB  - Within T cell-rich areas of secondary lymphoid organs, interdigitating dendritic
      cells recruit antigen-specific T cells that then induce B cells to secrete Igs.
      This study investigates the possible role(s) of dendritic cells in the regulation
      of human B cell responses. In the absence of exogenous cytokines, in vitro
      generated dendritic cells (referred to as Dendritic Langerhans cells, D-Lc)
      induced surface IgA expression on approximately 10% of CD40-activated naive sIgD+
      B cells. In the presence of IL-10 and TGF-beta, a combination of cytokines
      previously identified for its capacity to induce IgA switch, D-Lc strongly
      potentiated the induction of sIgA on CD40-activated naive B cells from 5% to 40
      50%. D-Lc alone did not induce the secretion of IgA by CD40-activated naive B
      cells, which required further addition of IL-10. Furthermore, D-Lc skewed towards
      the IgA isotype at the expense of IgG, the Ig production of CD40-activated naive
      B cells cultured in the presence of IL-10 and TGF-beta. Importantly, under these
      culture conditions, both IgA1 and IgA2 were detected. In the presence of IL-10,
      secretion of IgA2 by CD40-activated naive B cells could be detected only in
      response to D-Lc and was further enhanced by TGF-beta. Collectively, these
      results suggest that in addition to activating T cells in the extrafollicular
      areas of secondary lymphoid organs, human D-Lc also directly modulate T cell
      dependent B cell growth and differentiation, by inducing the IgA isotype switch.

PMID- 9166421
TI  - Influence of the NH2-terminal amino acid of the T cell receptor alpha chain on
      major histocompatibility complex (MHC) class II + peptide recognition.
AB  - The alpha/beta T cell receptor (TCR) recognizes peptide fragments bound in the
      groove of major histocompatibility complex (MHC) molecules. We modified the TCR
      alpha chain from a mouse T cell hybridoma and tested its ability to reconstitute
      TCR expression and function in an alpha chain-deficient variant of the hybridoma.
      The modified alpha chain differed from wild type only in its leader peptide and
      mature NH2-terminal amino acid. Reconstituted cell surface TCR complexes reacted
      normally with anti-TCR and anti-CD3 antibodies. Although cross-linking of this
      TCR with an antibody to the TCR idiotype elicited vigorous T cell hybridoma
      activation, stimulation with its natural MHC + peptide ligand did not. We
      demonstrated that this phenotype could be reproduced simply by substituting the
      glutamic acid (E) at the mature NH2 terminus of the wild type TCR alpha chain
      with aspartic acid (D). The substitution also dramatically reduced the affinity
      of soluble alpha/beta-TCR heterodimers for soluble MHC + peptide molecules in a
      cell-free system, suggesting that it did not exert its effect simply by
      disrupting TCR interactions with accessory molecules on the hybridoma. These
      results demonstrate for the first time that amino acids which are not in the
      canonical TCR complementarity determining regions can be critical in determining
      how the TCR engages MHC + peptide.

PMID- 9166422
TI  - N-Propionylated group B meningococcal polysaccharide mimics a unique bactericidal
      capsular epitope in group B Neisseria meningitidis.
AB  - The N-propionylated group B meningococcal polysaccharide (NPrGBMP) mimics a
      unique protective epitope on the surface of group B meningococci (GBM) and
      Escherichia coli K1. Using a series of monoclonal antibodies (mAbs) induced by
      the NPrGBMP-monomeric tetanus toxoid (TT) conjugate vaccine it was demonstrated
      that mAbs having specificities for both extended and conventional short segments
      of the NPrGBMP were formed, but only the former were bactericidal, and/or gave
      passive protection against live challenge by GBM. The failure of mAbs specific
      for short epitopes to protect was further established when (NeuPr)4-TT was used
      as the vaccine. Of all the mAbs produced that were specific for short internal
      segments of the NPrGBMP, none were protective, despite the fact that most of them
      cross-react with the GBM capsular polysaccharide. In contrast, most of the
      protective mAbs produced by NPrGBMP- TT did not recognize the group B
      meningococcal polysaccharide (GBMP) unless it was present in its aggregated high
      molecular weight form. The bactericidal epitope mimicked by the NPrGBMP was shown
      to be ubiquitous in the capsule of both GBM and E. coli K1 using immunogold
      labeling techniques and, because of its unique properties, its identification
      could be significant in the development of a comprehensive conjugate vaccine
      against group B meningococcal meningitis. This is because most known human
      alpha(2-8)-polysialic acid self-antigens can be accommodated in 30-50 alpha(2-8)
      linked sialic acid residues, which is roughly equivalent to an 11-kD length of
      the GBMP. It has been hypothesized that the formation of the protective epitope
      on the surface of GBM is due to the interaction of helical segments of the GBMP
      with another molecule and that the protective epitope is mimicked by the NPrGBMP.
      Support for the above hypothesis is provided by the fact that the protective
      NPrGBMP epitope has a similar unusual length dependency to that of the GBMP
      epitope.

PMID- 9166423
TI  - Crucial role of the residue R280 at the F'-G' loop of the human
      granulocyte/macrophage colony-stimulating factor receptor alpha chain for ligand
      recognition.
AB  - The receptor for granulocyte/macrophage colony-stimulating factor (GM-CSF) is
      composed of two chains, alpha and betac. Both chains belong to the superfamily of
      cytokine receptors characterized by a common structural feature, i.e., the
      presence of at least two fibronectin-like folds in the extracellular domain,
      which was first identified in the growth hormone receptor. The GM-CSF receptor
      (GMR)-alpha chain confers low affinity binding only (5-10 nM), whereas the other
      chain, betac, does not bind GM-CSF by itself but confers high affinity binding
      when associated with GMR-alpha (25-100 pM). The present study was designed to
      define the assembly of the GMR complex at the molecular level through site
      directed mutagenesis guided by homology modeling with the growth hormone receptor
      complex. In our three-dimensional model, R280 of GMR-alpha, located in the F'-G'
      loop and close to the WSSWS motif, is in the vicinity of the ligand Asp112,
      suggesting the possibility of electrostatic interaction between these two
      residues. Through site directed mutagenesis, we provide several lines of evidence
      indicating the importance of electrostatic interaction in ligand-receptor
      recognition. First, mutagenesis of GMR-alphaR280 strikingly ablated ligand
      binding in the absence of beta common (betac); ligand binding was restored in the
      presence of betac with, nonetheless, a significant shift from high (26 pM) toward
      low affinity (from 2 to 13 nM). The rank order of the dissociation constant for
      the different GMR-alphaR280 mutations where Lys > Gln > Met > Asp, suggesting the
      importance of the charge at this position. Second, a mutant GM-CSF with charge
      reversal mutation at position Asp112 exhibited a 1,000-fold decrease in affinity
      in receptor binding, whereas charge ablation or conservative mutations were the
      least affected (10-20-fold). Third, removal of the charge at position R280 of GMR
      alpha introduced a 10-fold decrease in the association rate constant and only a 2
      fold change in the dissociation rate constant, suggesting that R280 is implicated
      in ligand recognition, possibly through interaction with Asp112 of GM-CSF. For
      all R280 mutants, the half-efficient concentrations of GM-CSF required for
      membrane (receptor binding) to nuclear events (c-fos promoter activation) and
      cell proliferation (thymidine incorporation) were in the same range, indicating
      that the threshold for biologic activity is governed mainly by the affinity of
      ligand-receptor interaction. Furthermore, mutation of other residues in the
      immediate vicinity of R280 was less drastic. Sequence alignment and modeling of
      interleukin (IL)-3R and IL-5R identified an arginine residue at the tip of a beta
      turn in a highly divergent context at the F'-G' loop, close to a conserved
      structural element, the WSXWS motif, suggesting the possibility of a ligand
      association mechanism similar to the one described herein for GMR.

PMID- 9166424
TI  - Isolation, structure elucidation, and synthesis of a macrophage stimulatory
      lipopeptide from Mycoplasma fermentans acting at picomolar concentration.
AB  - Macrophages are typically stimulated by components of microbial cell walls.
      Surprisingly, cell wall-less mycoplasmas can also very efficiently stimulate
      macrophages. We showed recently that mycoplasma-derived lipopeptides constitute
      the active principle. We have now isolated a clone of Mycoplasma fermentans
      expressing mainly one macrophage-stimulating lipopeptide. This lipopeptide was
      detergent-extracted and isolated by reversed-phase high-performance liquid
      chromotography, using nitric oxide release from C3H/HeJ mouse macrophages as
      bioassay for detection. In contrast to "conventional" bacterial lipoproteins,
      this lipopeptide had a free NH2 terminus. Amino acid composition, sequence, and
      the molecular weight of 2,163. 3 are consistent with the following structure: S
      (2, 3-bisacyloxypropyl)cysteine-GNNDESNISFKEK with one mole C16:0, and a further
      mole of a mixture of C18:0 and C18:1 fatty acid per lipopeptide molecule. The
      sequence could not be found in either the protein identification resource nor the
      Swiss Prot data bank. We named this 2-kD lipopeptide, macrophage-activating
      lipopeptide-2 (MALP-2). Synthetic dipalmitoyl MALP-2 and mycoplasma-derived MALP
      2 were compared with the bioassay. Both lipopeptides showed an identical dose
      dependency with a half-maximal response at 10(-11) M concentration. MALP-2 may be
      one of the most potent natural macrophage stimulators besides endotoxin.

PMID- 9166425
TI  - Impaired host defense, hematopoiesis, granulomatous inflammation and type 1-type
      2 cytokine balance in mice lacking CC chemokine receptor 1.
AB  - CC chemokine receptor 1 (CCR1) is expressed in neutrophils, monocytes,
      lymphocytes, and eosinophils, and binds the leukocyte chemoattractant and
      hematopoiesis regulator macrophage inflammatory protein (MIP)-1alpha, as well as
      several related CC chemokines. Four other CCR subtypes are known; their leukocyte
      and chemokine specificities overlap with, but are not identical to, CCR1,
      suggesting that CCR1 has both redundant and specific biologic roles. To test
      this, we have developed CCR1-deficient mice (-/-) by targeted gene disruption.
      Although the distribution of mature leukocytes was normal, steady state and
      induced trafficking and proliferation of myeloid progenitor cells were disordered
      in -/- mice. Moreover, mature neutrophils from -/- mice failed to chemotax in
      vitro and failed to mobilize into peripheral blood in vivo in response to MIP
      1alpha. Consistent with this, -/- mice had accelerated mortality when challenged
      with Aspergillus fumigatus, a fungus controlled principally by neutrophils. To
      test the role of CCR1 in granuloma formation, we injected Schistosoma mansoni
      eggs intravenously, and observed a 40% reduction in the size of lung granulomas
      in -/- mice compared to +/+ littermates. This was associated with increased
      interferon-gamma and decreased interleukin-4 production in -/- versus +/+ lung
      lymph node cells stimulated with egg-specific antigen, suggesting that CCR1
      influences the inflammatory response not only through direct effects on leukocyte
      chemotaxis, but also through effects on the type 1-type 2 cytokine balance. Thus
      CCR1 has nonredundant functions in hematopoiesis, host defense, and inflammation.

PMID- 9166426
TI  - T cell receptor-gamma/delta cells protect mice from herpes simplex virus type 1
      induced lethal encephalitis.
AB  - Increased numbers of T cell receptor (TCR)-gamma/delta cells have been observed
      in animal models of influenza and sendai virus infections, as well as in patients
      infected with human immunodeficiency virus and herpes simplex virus type 1 (HSV
      1). However, a direct role for TCR-gamma/delta cells in protective immunity for
      pathogenic viral infection has not been demonstrated. To define the role of TCR
      gamma/delta cells in anti-HSV-1 immunity, TCR-alpha-/- mice treated with anti-
      TCR-gamma/delta monoclonal antibodies or TCR-gamma/delta x TCR-alpha/beta double
      deficient mice were infected with HSV-1 by footpad or ocular routes of infection.
      In both models of HSV-1 infection, TCR-gamma/delta cells limited severe HSV-1
      induced epithelial lesions and greatly reduced mortality by preventing the
      development of lethal viral encephalitis. The observed protection resulted from
      TCR-gamma/delta cell-mediated arrest of both viral replication and
      neurovirulence. The demonstration that TCR-gamma/delta cells play an important
      protective role in murine HSV-1 infections supports their potential contribution
      to the immune responses in human HSV-1 infection. Thus, this study demonstrates
      that TCR-gamma/delta cells may play an important regulatory role in human HSV-1
      infections.

PMID- 9166427
TI  - Selective suppression of interleukin-12 induction after macrophage receptor
      ligation.
AB  - Interleukin (IL)-12 is a monocyte- and macrophage-derived cytokine that plays a
      crucial role in both the innate and the acquired immune response. In this study,
      we examined the effects that ligating specific macrophage receptors had on the
      induction of IL-12 by lipopolysaccharide (LPS). We report that ligation of the
      macrophage Fcgamma, complement, or scavenger receptors inhibited the induction of
      IL-12 by LPS. Both mRNA synthesis and protein secretion were diminished to near
      undetectable levels following receptor ligation. Suppression was specific to IL
      12 since IL-10 and tumor necrosis factor-alpha (TNF-alpha) production were not
      inhibited by ligating macrophage receptors. The results of several different
      experimental approaches suggest that IL-12 downregulation was due to
      extracellular calcium influxes that resulted from receptor ligation. First,
      preventing extracellular calcium influxes, by performing the assays in EGTA,
      abrogated FcgammaR-mediated IL-12(p40) mRNA suppression. Second, exposure of
      macrophages to the calcium ionophores, ionomycin or A23187, mimicked receptor
      ligation and inhibited IL-12(p40) mRNA induction by LPS. Finally, bone marrow
      derived macrophages from FcR gamma chain-deficient mice, which fail to flux
      calcium after receptor ligation, failed to inhibit IL-12(p40) mRNA induction.
      These results indicate that the calcium influxes that occur as a result of
      receptor ligation are responsible for inhibiting the induction of IL-12 by LPS.
      Hence, the ligation of phagocytic receptors on macrophages can lead to a dramatic
      decrease in IL-12 induction. This downregulation may be a way of limiting
      proinflammatory responses of macrophages to extracellular pathogens, or
      suppressing the development of cell-mediated immunity to intracellular pathogens.

PMID- 9166428
TI  - Regulation of interleukin-12 by complement receptor 3 signaling.
AB  - Complement receptor type 3 (CR3, CD11b/CD18) serves as a receptor for a number of
      endogenous ligands and infectious organisms, and is involved in adhesion and host
      defense functions. Here, we report that signaling via CR3 plays an important role
      in regulating production of interleukin-12 (IL-12), a key mediator of cell
      mediated immunity (CMI). We demonstrate with a variety of stimuli a dose
      dependent, specific downregulation of IL-12 secretion by human monocytes in vitro
      after exposure to antibodies to CR3 (anti-CD11b and anti-CD18), as well as to the
      natural CR3 ligands, iC3b, and Histoplasma capsulatum. CR3 antibodies also
      suppressed interferon-gamma (IFN-gamma) production in cultures of human
      peripheral blood mononuclear cells (PBMC). We determined that one mechanism by
      which CR3 antibodies may suppress IL-12 production is by the inhibition of IFN
      gamma-induced tyrosine phosphorylation. Finally, in a murine model of IL-12
      dependent septic shock, we provide evidence that administration of CR3 antibodies
      leads to suppression of IL-12 and IFN-gamma in vivo. Our studies thus define a
      novel role for CR3 in regulating CMI functions via IL-12.

PMID- 9166429
TI  - 9-O-Acetylation of sialomucins: a novel marker of murine CD4 T cells that is
      regulated during maturation and activation.
AB  - Terminal sialic acids on cell surface glycoconjugates can carry 9-O-acetyl
      esters. For technical reasons, it has previously been difficult to determine
      their precise distribution on different cell types. Using a recombinant soluble
      form of the Influenza C virus hemagglutinin-esterase as a probe for 9-O
      acetylated sialic acids, we demonstrate here their preferential expression on the
      CD4 T cell lineage in normal B10.A mouse lymphoid organs. Of total thymocytes, 8
      10% carry 9-O-acetylation; the great majority of these are the more mature PNA-,
      HSA-, and TCRhi medullary cells. While low levels of 9-O-acetylation are seen on
      some CD4/CD8 double positive (DP) and CD8 single positive (SP) cells, high levels
      are present primarily on 80- 85% of CD4 SP cells. Correlation with CD4 and CD8
      levels suggests that 9-O-acetylation appears as an early differentiation marker
      as cells mature from the DP to the CD4 SP phenotype. This high degree of 9-O
      acetylation is also present on 90-95% of peripheral spleen and lymph node CD4 T
      cells. In contrast, only a small minority of CD8 T cells and B cells show such
      levels of 9-O-acetylation. Among mature peripheral CD4 T lymphocytes, the highly
      O-acetylated cells are Mel 14(hi), CD44(lo), and CD45R(exon B)hi, features
      typical of naive cells. Digestions with trypsin and O-sialoglycoprotease
      (OSGPase) and ELISA studies of lipid extracts indicate that the 9-O-acetylated
      sialic acids on peripheral CD4 T cells are predominantly on O-linked mucintype
      glycoproteins and to a lesser degree, on sialylated glycolipids (gangliosides).
      In contrast, sialic acids on mucin type molecules of CD8 T cells are not O
      acetylated; instead these molecules mask the recognition of O-acetylated
      gangliosides that seem to be present at similar levels as on CD4 cells. The 9-O
      acetylated gangliosides on mouse T cells are not bound by CD60 antibodies, which
      recognize O-acetylated gangliosides in human T cells. Tethering 9-O-acetylated
      mucins with the Influenza C probe with or without secondary cross-linking did not
      cause activation of CD4 T cells. However, activation by other stimuli including
      TCR ligation is associated with a substantial decrease in surface 9-O
      acetylation, primarily in the mucin glycoprotein component. Thus, 9-O-acetylation
      of sialic acids on cell surface mucins is a novel marker on CD4 T cells that
      appears on maturation and is modulated downwards upon activation.

PMID- 9166430
TI  - STRL33, A novel chemokine receptor-like protein, functions as a fusion cofactor
      for both macrophage-tropic and T cell line-tropic HIV-1.
AB  - The chemokine receptors CXCR4, CCR2B, CCR3, and CCR5 have recently been shown to
      serve along with CD4 as coreceptors for HIV-1. The tropisms of HIV-1 strains for
      subgroups of CD4(+) cells can be explained, at least partly, by the selective use
      of G protein-coupled receptors (GPCRs). We have identified a novel human gene,
      STRL33, located on chromosome 3 that encodes a GPCR with sequence similarity to
      chemokine receptors and to chemokine receptor-like orphan receptors. STRL33 is
      expressed in lymphoid tissues and activated T cells, and is induced in activated
      peripheral blood lymphocytes. When transfected into nonhuman NIH 3T3 cells
      expressing human CD4, the STRL33 cDNA rendered these cells competent to fuse with
      cells expressing HIV-1 envelope glycoproteins (Envs). Of greatest interest,
      STRL33, in contrast with CXCR4 or CCR5, was able to function as a cofactor for
      fusion mediated by Envs from both T cell line-tropic and macrophage-tropic HIV-1
      strains. STRL33-transfected Jurkat cell lines also supported enhanced productive
      infection with HIV-1 compared with control Jurkat cells. Despite the sequence
      similarities between STRL33 and chemokine receptors, STRL33-transfected cell
      lines did not respond to any in a panel of chemokines. Based on the pattern of
      tissue expression of the STRL33 mRNA, and given the ability of STRL33 to function
      with Envs of differing tropisms, STRL33 may play a role in the establishment
      and/or progression of HIV-1 infection.

PMID- 9166431
TI  - V(D)J recombination: modulation of RAG1 and RAG2 cleavage activity on 12/23
      substrates by whole cell extract and DNA-bending proteins.
AB  - Antigen receptor gene rearrangement is directed by DNA motifs consisting of a
      conserved heptamer and nonamer separated by a nonconserved spacer of either 12 or
      23 base pairs (12 or 23 recombination signal sequences [RSS]). V(D)J
      recombination requires that the rearranging DNA segments be flanked by RSSs of
      different spacer lengths, a phenomenon known as the 12/23 rule. Recent studies
      have shown that this restriction operates at the level of DNA cleavage, which is
      mediated by the products of the recombination activating genes RAG1 and RAG2.
      Here, we show that RAG1 and RAG2 are not sufficient for 12/23 dependent cleavage,
      whereas RAG1 and RAG2 complemented with whole cell extract faithfully
      recapitulates the 12/23 rule. In addition, HMG box containing proteins HMG1 and
      HMG2 enhance RAG1- and RAG2-mediated cleavage of substrates containing 23 RSS but
      not of substrates containing only 12 RSS. These results suggest the existence of
      a nucleoprotein complex at the cleavage site, consisting of architectural,
      catalytic, and regulatory components.

PMID- 9166433
TI  - Temporal variations in the infection of a population of Clypeomorus bifasciata
      (Gastropoda: Prosobranchia) by a digenean microphallid larva in Kuwait Bay.
AB  - The prosobranch snail Clypeomorus bifasciata in Kuwait Bay was examined for
      digenean infections over a one year period during 1994/1995. A total of 1500
      snails was examined and 567 (37.8%) were found to harbour nine digenean species.
      The prevalence of a microphallid species was 33.9% while each of the others
      occurred in less than 1.2% of the snails. The prevalence of infection increased
      with shell size. Multiple infections were observed in only five of the infected
      snails and the microphallid was involved in all of them. Snails were infected
      with the microphallid throughout the year and there appeared to be two peaks in
      the proportion of infected snails shedding cercariae, a winter peak from November
      to January and a summer peak from June to August. The crab Xantho exaratus
      collected from snail sampling sites was heavily parasitized by microphallid
      metacercariae of the genera Longiductotrema and Microphallus. This is the first
      report on microphallid metacercariae in crabs in the Arabian Gulf region.

PMID- 9166432
TI  - Thymus-derived glucocorticoids regulate antigen-specific positive selection.
AB  - While it is generally believed that the avidity of the T cell antigen receptor
      (TCR) for self antigen/major histocompatibility complex (MHC) determines a
      thymocyte's fate, how the cell discriminates between a stimulus that causes
      positive selection (survival) and one that causes negative selection (death) is
      unknown. We have previously demonstrated that glucocorticoids are produced in the
      thymus, and that they antagonize deletion caused by TCR cross-linking. To examine
      the role of glucocorticoids during MHC-dependent selection, we examined thymocyte
      development in organ cultures in which corticosteroid biosynthesis was inhibited.
      Inhibition of glucocorticoid production in thymi from alpha/beta-TCR transgenic
      mice resulted in the antigen- and MHC-specific loss of thymocytes that normally
      recognize self antigen/MHC with sufficient avidity to result in positive
      selection. Furthermore, inhibition of glucocorticoid production caused an
      increase in apoptosis only in CD+CD8(+) thymocytes bearing transgenic TCRs that
      recognized self antigen/MHC. These results indicate that the balance of TCR and
      glucocorticoid receptor signaling influences the antigen-specific thymocyte
      development by allowing cells with low-to-moderate avidity for self antigen/MHC
      to survive.

PMID- 9166434
TI  - The structure and formation of metacercarial cysts in the trematode family
      Microphallidae travassos 1920.
AB  - This study deals with the formation of the metacercarial cysts of four
      microphallid trematodes, Maritrema subdolum, M. arenaria, Levinseniella
      brachysoma and Microphallus claviformis. The first observable cyst was present
      around Maritrema arenaria 18 h p.i. (post-infection). The other species had not
      developed a cyst by day 8 p.i. but their cysts were apparent by day 16 p.i. These
      were bi-layered and that of M. subdolum was thicker than those of L. brachysoma
      and Microphallus claviformis of the same age. The structure of older cysts varied
      substantially between the four species. Microphallus claviformis and Maritrema
      subdolum cysts were fully formed at 30 days p.i. Like those of M. arenaria they
      were bi-layered, the outer layer (up to 3 microm thick) being electron-dense and
      the inner one (up to 7 microm thick) being less electron-dense. The cysts of
      fully formed L. brachysoma metacercariae were much more complex, composed of four
      layers, one of which was divisible into three sub-layers. It was concluded that
      the outer cyst layer was the product of secretory granules which were previously
      identified in cercarial tegument. The inner, thicker layer was derived from
      several sources. These included small tegument vesicles produced over the entire
      surface of the metacercariae, larger fragments of tegument released from the
      anterio-ventral region and material liberated from the metacercarial excretory
      bladder. This heterogeneous material accumulated in the cyst lumen for some time
      before becoming polymerized to form the thick inner layer or layers of the
      metacercarial cysts.

PMID- 9166435
TI  - Echinococcus multilocularis: mouse strain difference in hydatid development.
AB  - Female mice of nine inbred strains (A, AKR, BALB/c, C3H, C57BL/6, C57BL/10, CBA,
      DBA/1 and DBA/2) and H-2 congenic B10.D2, at 9-10 weeks of age, were infected
      with larval Echinococcus multilocularis by trans-portal injection of hydatid
      homogenate. Parasitized livers were histologically examined 9 or 13 weeks after
      infection. Hydatid development was quite different among mouse strains.
      Multivesiculation was prominent in C57BL/10, DBA/1, C57BL/6 and BALB/c.
      Protoscoleces were well developed in DBA/2, AKR, DBA/1 and CBA. H-2 congenic
      B10.D2, which has the background genes of C57BL/10 except for the H-2d gene of
      DBA/2, resembled C57BL/10 in prohibiting the development of protoscoleces. These
      data suggest that the qualitative difference in hydatid development may be
      regulated by non-H-2 gene(s).

PMID- 9166436
TI  - Composition and structure of helminth communities in eels Anguilla anguilla from
      Italian coastal lagoons.
AB  - The composition and diversity of total and intestinal helminth component and
      infracommunities were determined in eels Anguilla anguilla from four shallow
      coastal lagoons near Rome. The lagoons differed principally in respect of their
      salinity. Only Lake Burano still received an input of freshwater, and both
      freshwater and marine helminth species were found in eels. In the other three
      lagoons all helminth species were marine or euryhaline and communities were
      dominated by digeneans. At component community level these three lagoons were far
      more similar to each other than to Lake Burano, but this distinction almost
      disappeared at infracommunity level. Species richness and diversity declined with
      increasing salinity at component community level but not at infracommunity level.
      Despite the changes and differences in helminth community composition, intestinal
      helminth infracommunity structure was very similar in all four lagoons and to
      that in eels from freshwater localities in Britain. The findings thus provide
      further and unexpected support for the view that some factor(s) other than supply
      side ones must be operating to produce the fundamental structural similarity in
      helminth communities in eels.

PMID- 9166438
TI  - Ostertagia nianqingtanggulaensis Kung & Li, 1965 (Nematoda: Trichostrongyloidea)
      from sheep and goats at high altitudes in Nepal.
AB  - The trichostrongyloid nematode Ostertagia nianqingtanggulaensis Kung & Li, 1965,
      previously recorded only from sheep in Tibet, is redescribed and is shown to be a
      common parasite of both sheep and goats at higher altitudes in the Himalayan
      foothills of western Nepal. Herbage examination indicated that infective larvae
      can overwinter on snow covered slopes. Use of tracer animals confirmed that
      migratory flocks are exposed to infection when grazing on alpine pastures during
      the summer months. In contrast, nearby non-migratory flocks kept at lower
      altitudes did not harbour O. nianqingtanggulaensis and tracer animals grazed with
      these flocks did not become infected with this species.

PMID- 9166437
TI  - Preliminary biochemical characterization of faeces from uninfected rats and rats
      infected with the tapeworm, Hymenolepis diminuta.
AB  - Faecal pellets were collected from uninfected rats and rats infected with
      Hymenolepis diminuta, and analysed for caloric value, lipids, carbohydrates,
      glucose, amino acids, and proteins. Faeces from infected rats contained
      significantly more lipid and less carbohydrate and glucose than faeces from
      control rats. The total free amino acid content of faeces from infected and
      control rats did not differ, but there were significant differences in the
      amounts of individual free amino acids. The data support the hypothesis that the
      nutrient composition of faeces from infected and control hosts differ. Beetles
      that serve as the intermediate host for H. diminuta may be able to detect these
      differences, and this may explain why beetles preferentially ingest faeces
      containing the tapeworm s eggs.

PMID- 9166439
TI  - Echinococcus granulosus: characterization of the Spanish strains using in vitro
      vesicular development.
AB  - Differences in in vitro vesicular development (microcyst formation) in three
      Spanish strains of Echinococcus granulosus (sheep-cattle, horse and pig-goat) are
      reported. Microcyst formation occurred in 19-37 days (sheep strain), 9-18 days
      (pig strain) and 35-47 days (horse strain). Comparing these results with those
      from human samples (microcyst formation in 24-38 days), it is possible to
      consider the sheep strain as the most likely source of human infections in Spain.

PMID- 9166440
TI  - Desiccation survival of populations of the entomopathogenic nematodes Steinernema
      feltiae and Heterorhabditis megidis from Greece and the UK.
AB  - The desiccation survival and ability to control water loss during drying of
      individual infective juveniles (IJs) of populations of Steinernema feltiae and
      Heterorhabditis megidis from Greece and the UK were examined at different
      relative humidities. Survival at all relative humidities was for minutes only and
      there was no evidence of enhanced survival of the populations of either species
      from Greece compared with those from the UK. The survival of individuals of both
      populations of H. megidis was superior to that of S. feltiae and the rate of
      drying of H. megidis was significantly slower. The sheath surrounding the IJs of
      H. megidis appears to be involved in slowing the rate of water loss of the
      enclosed nematodes.

PMID- 9166441
TI  - Intraspecific variation in Schistosoma haematobium from Algeria.
AB  - A comparative analysis has been carried out between two populations of
      Schistosoma haematobium using the same intermediate snail host, Bulinus
      truncatus, but originating from two distinct ecological areas of Algeria: Khemis
      El-Khechna in a sub-humid mediterranean zone and Djanet in a saharan bioclimatic
      zone. Four parameters have been studied: the growth rate of adult worms, size and
      shape of the eggs, chronobiology of cercarial emergence and the compatibility
      with the intermediate host. Results showing divergences for all the characters
      studied are discussed for the origin of this intraspecific polymorphism of S.
      haematobium in Algeria.

PMID- 9166442
TI  - The in vitro effect of Khawia sinensis on leucocyte activity in carp (Cyprinus
      carpio).
AB  - The interactions between Khawia sinensis (Cestoda: Caryophyllidea), a pathogenic
      tapeworm of carp, and host leucocytes has been investigated in vitro by
      monitoring blastogenesis in pronephric, splenic and thymic lymphocytes and
      apoptosis of pronephric leucocytes. Both parasite homogenate and
      excretory/secretory (E/S) products were found to suppress lymphocyte
      blastogenesis at high concentrations (346.6-98.8 microg ml-1) whilst cell
      stimulation occurred at low concentrations (49.4-19.8 microg ml-1). This
      differential affect on leucocyte activity may not be associated with apoptosis in
      vitro as the parasite E/S products did not significantly affect programmed cell
      death as monitored by acridine orange and DNA analysis. The parasite effect on
      leucocyte activity is discussed and its relationship to host susceptibility is
      evaluated.

PMID- 9166443
TI  - Primers for polymerase chain reaction to detect genomic DNA of Toxocara canis and
      T. cati.
AB  - Primers for polymerase chain reaction to amplify genomic DNA of both Toxocara
      canis and T. cati were constructed by adapting cloning and sequencing random
      amplified polymorphic DNA. The primers are expected to detect eggs and/or larvae
      of T. canis and T. cati, both of which are known to cause toxocariasis in humans.

PMID- 9166444
TI  - Growth and development of Gnathostoma spinigerum early third-stage larvae in
      vitro.
AB  - Early third-stage larvae of Gnathostoma spinigerum were cultured in RPMI-1640
      supplemented with 25mM NaHCO3,100 units/ml penicillin G, 100 microg/ml of
      streptomycin, 5 microg/ml of amphotericin B and 10% foetal calf serum at 37
      degrees C under 5% CO2 in air for 60 days. After 3 days of cultivation, the
      larvae moulted. Body sizes increased from 0.49 +/- 0.09 x 0.07 +/- 0.01 mm in
      length and width to 4.08 +/- 0.48 x 0.32 +/- 0.04 mm after 60 days of
      cultivation. The maximum body length and width of these larvae were 4.94 mm and
      0. 35 mm, respectively. The survival rate (67.5 %) of the worms was observed at
      the end of cultivation. The addition of foetal calf serum was found to be
      essential for growth and development.

PMID- 9166445
TI  - Genomic identification of Anisakis simplex isolates.
AB  - RAPD technique was used to differentiate individuals of Anisakis simplex obtained
      from Merluccius merluccius, Phycis blennoides, Conger conger and Lepidorhombus
      boscii, from the North Atlantic Ocean. The amplification patterns of the host DNA
      controls were markedly different from those obtained for the parasitic material.
      No variation within the same host was detected. The amplification patterns for
      larvae obtained from fish of the same genus were somewhat different. The
      amplification patterns of A. simplex isolates from M. merluccius, P. blennoides,
      C. conger and L. boscii, were different. These results suggest the possible
      existence of two populations with a considerable high genetic variability and a
      different adaptation to different host species.

PMID- 9166446
TI  - Serological evidence of toxocariasis in patients from Spain with a clinical
      suspicion of visceral larva migrans.
AB  - Sera from patients with clinical characteristics of toxocariasis were assayed
      using the ELISA method and larval excretory-secretory antigen. Four hundred and
      seven samples of Toxocara serology were received at the laboratory of Ciudad
      Sanitaria Juan Canalejo Hospital of Corunna, Spain, from 1984 to 1989. Of these,
      30 were from adults, 332 from children and 45 from patients of unknown age,
      resulting in Toxocara seroprevalences of 23.3%, 32.8% and 17.7% respectively. The
      reasons for these serological differences in the rural and urban areas of
      Galicia, Spain are discussed.

PMID- 9166447
TI  - The cell cycle: Probing new molecular determinants of resistance and sensitivity
      to cytotoxic agents.
AB  - The introduction of chemotherapy in the fifth and sixth decades of this century
      has resulted in the development of curative therapeutic interventions for
      patients with several types of solid tumors and hematopoietic neoplasms. The
      important obstacles encountered in the use of chemotherapy have been toxicity on
      the normal tissues of the body and the presence of mutations that confer
      resistance to these chemotherapeutic agents. During the past 5 years, the
      application of molecular analysis to the DNA of normal and neoplastic cells has
      uncovered some of the mechanisms through which chemotherapy induces cell death,
      and the changes within these cells that can confer either sensitivity or
      resistance to these cells. This new level of understanding of the mechanisms
      through which chemotherapy works, and by which genetic change can result in
      resistance to this therapy, has opened the door to totally new paradigms of
      treatment. These paradigms use molecular, genetic, and biologic therapies
      together to increase the sensitivity of abnormal cells to treatment, and to
      protect the normal tissues of the body from therapy-induced side effects. The
      implementation of these new strategies, which is already well under way, promises
      to dramatically change the way in which therapy is delivered over the next few
      years, and to improve the outcome especially in patients with neoplasms that
      currently are resistant to conventional dose therapy.

PMID- 9166448
TI  - The cost-benefit ratio of the cure of Hodgkin's disease.

PMID- 9166449
TI  - Sherlock Holmes and the case of hypoxia.

PMID- 9166450
TI  - Growth factors alter the therapeutic ratio in radiotherapy.

PMID- 9166451
TI  - Percutaneous radiofrequency interstitial thermal ablation.

PMID- 9166452
TI  - Long-term survival in Hodgkin's disease relative impact of mortality, second
      tumors, infection, and cardiovascular disease.
AB  - PURPOSE: Despite dramatic improvements in the survival of patients with Hodgkin's
      disease attributable to advances in treatment over the past 30 years, concern for
      the risk of treatment-related deaths has led to a number of trials to evaluate
      reduction of therapy. The consequences of these trials on recurrence, development
      of long-term complications, and survival remain unknown. We determined the causes
      of death in a group of patients with pathologically staged and intensively
      treated Hodgkin's disease who were followed for long intervals. MATERIALS AND
      METHODS: Between April 1969 and December 1988, 794 patients with laparotomy
      staged IA to IIIB Hodgkin's disease were treated with radiation therapy alone or
      combined radiation therapy and chemotherapy. There were 8700 person-years of
      follow-up (average, 10.95 person-years/ patient). Causes of mortality were
      grouped into the categories Hodgkin's disease, second malignant tumors,
      cardiovascular, infection, and miscellaneous. Age- and gender-specific incidence
      rates were multiplied by corresponding person-years of observation to obtain
      expected numbers of events. Observed-to-expected results were calculated by type
      of treatment, age at treatment, sex, and time after Hodgkin's disease. Absolute
      (excess) risk was expressed as number of excess cases per 10,000 person-years.
      RESULTS: Of 124 patients who died, 56 died of Hodgkin's disease, 36 of second
      malignant neoplasms, 15 of cardiac causes, 9 of infection, and 8 of miscellaneous
      causes. The 20-year actuarial survival rate for all patients in this study is
      73%. Age 40 years or older, mixed cellularity/lymphocyte-depleted histologic
      type, and stage-III disease were adverse independent predictors of survival. The
      largest differences were seen by age. The 20-year actuarial rates of survival
      were 78%, 78%, and 46%, respectively, for patients aged 16 or less, 17 to 39, and
      40 years or older at diagnosis. Hodgkin's disease diagnosed at age 40 or older
      was a significant risk factor for all causes of death. The use of combined
      chemotherapy/ radiotherapy was a significant risk factor for second tumor and
      infection-related mortality. The excess risk of death from all causes, including
      Hodgkin's disease, remained constant with time from treatment and was
      approximately 1.2% per year over the first 20 years. Deaths from Hodgkin's
      disease decreased with time from treatment, with no patients dying after 15
      years. This decrease, combined with an increased excess mortality risk with time
      from other causes, especially second tumors, accounted for the constant excess
      mortality with time after Hodgkin's disease. CONCLUSIONS: Hodgkin's disease
      followed by second tumors, cardiac events, and infections remain the major causes
      of death after treatment of Hodgkin's disease. Our findings suggest the
      importance of both maintaining a high disease-free survival and reducing long
      term complications in designing treatments of Hodgkin's disease.

PMID- 9166453
TI  - Restoration of tumor oxygenation after cytotoxic therapy by a perflubron
      emulsion/carbogen breathing.
AB  - PURPOSE: Hypoxic cells are presumed to be an obstacle to successful cancer
      treatment because these cells are protected from the cytotoxic effects of
      radiotherapy and certain anti-cancer drugs. The current study was conducted to
      determine the effect of cytotoxic therapy on tumor oxygenation and the effect of
      administration of a perfluorochemical emulsion/carbogen breathing treatment on
      tumor oxygenation after cytotoxic therapy. MATERIALS AND METHODS: Female Fisher
      344 rats bearing 13762 mammary carcinoma cells implanted subcutaneously in a
      hindlimb were treated with standard therapeutic single doses of anti-tumor
      treatments of several types, including alkylating agents (cisplatin, melphalan,
      cyclophosphamide); natural products (doxorubicin, paclitaxel, etoposide);
      antimetabolites (fluorouracil); hypoxic cell-selective agents (mitomycin, SR
      4233); and fractionated irradiation (3 Gy/day for 5 days). The oxygen levels in
      the tumors were measured with an Eppendorf PO2 histograph before the treatment
      and 24 hours after treatment under air breathing and carbogen breathing
      conditions, and after administration of a perflubron emulsion under air breathing
      and carrbogen breathing conditions. Fifty to 60 points were measured per tumor,
      and 8 to 10 tumors made up each group. RESULTS: The tumors were more hypoxic
      after treatment with every anticancer treatment. The percentage of PO2 readings <
      or = 5 mmHg in the untreated tumors was 49% and ranged from 85% (radiotherapy) to
      59% (etoposide) in the treated tumors. Administration of the perflubron emulsion
      (8 mL/kg) and carbogen breathing (95% O2/5% CO2) increased the oxygenation of the
      tumors such that the percentage of PO2 readings < or = 5 mmHg was 32% in the
      untreated control tumors and ranged from 27% (radiotherapy) to 56% (doxorubicin)
      in the treated tumors. There was a direct correlation between the level of tumor
      cell killing and the increased oxygenation observed in the tumor. CONCLUSION:
      Tumors may be more hypoxic after an effective dose of a cytotoxic therapy, and
      administration of a perflubron emulsion/carbogen mixture can increase the tumor
      oxygen content when hypoxia is the result of cytotoxic therapy. Hypoxia produced
      by therapy may be regarded as a mechanism of resistance that leads to diminished
      tumor cell killing with subsequent doses of drugs or radiation. The restoration
      of tumor oxygenation by the perflubron emulsion/carbogen breathing may provide a
      clinically relevant means of overcoming at least in part hypoxia-related
      resistance.

PMID- 9166454
TI  - Thymidylate synthase protein expression: Association with response to neoadjuvant
      chemotherapy and resection for locally advanced gastric and gastroesophageal
      adenocarcinoma.
AB  - PURPOSE: A phase II study of neoadjuvant fluorouracil, leucovorin, and interferon
      alpha-2a was conducted to determine the feasibility of this regimen's use and the
      response rates in patients undergoing resection for locally advanced gastric or
      gastroesophageal adenocarcinoma. Also, tumor protein expression of free, total,
      or bound thymidylate synthase before and after initial exposure to fluorouracil
      was quantitated to determine if thymidylate synthase expression is associated
      with response in this treatment setting. PATIENTS AND METHODS: Twenty-two
      patients with T3-4N0-2M0 gastric or gastroesophageal adenocarcinoma were treated
      with three cycles of neoadjuvant fluorouracil (370 mg/m2 intravenously on days 2
      through 6), leucovorin (500 mg/m2 intravenously on days 2 through 6), and
      interferon alpha-2a (5x106 U/m2 subcutaneously days 1 through 7), followed by
      resection and three cycles of consolidation therapy. Endoscopic tumor biopsies
      were done in 13 patients before therapy and during cycle 2 of the 5
      fluorouracil/leucovorin/interferon regimen, and total thymidylate synthase, free
      thymidylate synthase, bound thymidylate synthase, and percent complexed
      thymidylate synthase were quantitated by Western blot. Tumor protein expression
      was evaluated for its association with response to neoadjuvant therapy and
      patient survival. RESULTS: Eight of 21 (38%) evaluable patients had a partial
      response, and another 5 of 21 (24%) had a minor response (25% to 49% tumor
      reduction) after three cycles of neoadjuvant fluorouracil/leucovorin/interferon.
      The pretreatment total thymidylate synthase level was significantly higher in
      five nonresponders than in eight responders. After exposure to fluorouracil,
      levels of free thymidylate synthase were significantly lower and the percent
      bound thymidylate synthase was higher in responders than in nonresponders. The
      median potential follow-up period is 24 months, and 11 of 21 patients have died
      from disease. CONCLUSIONS: These preliminary results indicate that a response to
      neoadjuvant fluorouracil-based therapy may be associated with decreased levels of
      total thymidylate synthase before therapy and free thymidylate synthase after
      exposure to fluorouracil in patients with locally advanced gastric cancer.
      Quantification of thymidylate synthase protein expression before and after
      exposure to fluorouracil may provide a method to select patients for fluorouracil
      therapy in the neoadjuvant, adjuvant, or advanced-disease setting based upon the
      fundamental sensitivity of the tumor.

PMID- 9166455
TI  - Local recurrence after conservative surgery and radiation therapy for ductal
      carcinoma in situ: Possible importance of family history.
AB  - PURPOSE: The optimal treatment of ductal carcinoma in situ is controversial.
      Traditionally, women with this disease have been treated with mastectomy with
      excellent results, but recently the need for such extensive surgery has been
      questioned. Long-term data on the use of conservative surgery and radiation
      therapy for treatment are limited. A retrospective analysis was performed to
      assess treatment outcome and prognostic factors for patients with ductal
      carcinoma in situ treated with conservative surgery and radiotherapy. PATIENTS
      AND METHODS: From 1976 to 1990, 76 women with ductal carcinoma in situ were
      treated with conservative surgery followed by radiation therapy. The median age
      at diagnosis was 48 years. Seventeen patients had a positive family history of
      breast cancer in a first-degree (n=8) or second-degree (n=9) relative. Median
      follow-up interval was 74 months for the 71 survivors. In 54 patients, the
      carcinoma was detected by mammography alone; in 13 patients, by mammography and
      physical examination; and in 4 patients, by physical examination with a normal
      mammogram; and in 5 patients, by physical examination alone without mammography.
      Fifty patients had re-excision after initial biopsy. Final margins were positive
      in 11, close in 11, negative in 34, and unknown in 20. The median volume of
      excised tissue was 60 cm3. The axilla was surgically staged in 30 patients (39%)
      and all were negative. The whole breast was irradiated to a dose of 45 to 50 Gy
      in all patients. Seventy-two patients also received a boost to the primary site.
      The median total radiation dose to the primary site was 61 Gy (range, 46 to 71).
      RESULTS: Seven patients had a recurrence in the treated breast at 16, 18, 41, 63,
      72, 83, and 104 months after treatment. The 5- and 10-year actuarial rates of
      local recurrence were 4% and 15%, respectively. Six of seven recurrences occurred
      in the vicinity of the original lesion. Four local recurrences were invasive, and
      three were ductal carcinoma in situ. Two patients developed a contralateral
      invasive carcinoma. The 5- and 10-year cause-specific survival rates were 100%
      and 96%, respectively. The 10-year actuarial rate of local recurrence was 25% in
      the group with a total excision volume less than 60 cm3, as compared with 0% in
      those with 60 cm3 or more excised (P=0.04). In patients with a positive family
      history, the 10-year actuarial rate of local recurrence was 37%, as compared with
      9% in patients with a negative family history (P=0.008). Of the 17 patients with
      a positive family history, four developed either an ipsilateral or contralateral
      invasive breast cancer, whereas 1 of the 58 patients without a family history
      developed a subsequent invasive breast cancer (P=0.008). CONCLUSION: These
      results suggest that patients with ductal carcinoma in situ treated with
      conservative surgery and radiotherapy (including a boost to the primary site)
      appear to benefit from wide, rather than limited, resection. These results also
      suggest that family history may be an important prognostic factor for progression
      of disease.

PMID- 9166456
TI  - Intravenous basic fibroblast growth factor protects the lung but not mediastinal
      organs against radiation-induced apoptosis in vivo.
AB  - PURPOSE: We evaluated the therapeutic potential of intravenously injected basic
      fibroblast growth factor against the lethal syndromes associated with irradiation
      of intrathoracic organs and assessed whether such protection might be associated
      with inhibition of programmed cell death (apoptosis) in the exposed tissues.
      MATERIALS AND METHODS: C3H/HeJ and C3H/scid mice received either whole-chest,
      mediastinal, or bilateral lung irradiation. Human recombinant basic fibroblast
      growth factor was injected intravenously at doses of 400 ng immediately before
      and after irradiation, and then at 1 hour and 2 hours later. Time-adjusted
      survival was calculated from the date of irradiation by the product-limit Kaplan
      Meier method. Detection of apoptotic changes in paraffin sections was performed
      by the DNA terminal transferase nick-end translation method. RESULTS: Basic
      fibroblast growth factor protected the lungs but not other intrathoracic organs
      against radiation-induced damage. When radiation was restricted to the lungs, the
      LD50/180 from radiation pneumonitis was 20.75 Gy and increased to 23.0 Gy in
      basic fibroblast growth factor-treated mice. When the whole thorax was
      irradiated, basic fibroblast growth factor partially protected against
      pneumonitis at the low range of radiation doses (< or = LD50/180), but failed to
      confer protection at higher doses, nor did it protect against lethal radiation
      esophagitis. Staining for the presence of apoptotic nuclei revealed time- and
      radiation dose-dependent development of apoptosis in endothelial cells of the
      pulmonary capillary network, endocardium, and mesothelial cells of the pleura and
      pericardium. Although basic fibroblast growth factor inhibited apoptosis in the
      microvascular endothelium and the endocardium, it had no effect on apoptosis in
      the serosal mesothelium of the pleura and pericardium. CONCLUSIONS: Intravenous
      basic fibroblast growth factor protects against the apoptotic microvascular
      component of early-phase radiation pneumonitis but may have no effect on other
      elements of the primary damage produced by radiation in the lungs and other
      intrathoracic organs. Understanding the patterns and temporal evolution of
      radiation-induced apoptosis and basic fibroblast growth factor-mediated
      antiapoptotic effects in thoracic organs and tumors may offer opportunities for
      pharmacologic intervention in the radiotherapeutic management of primary and
      metastatic lung tumors.

PMID- 9166457
TI  - Percutaneous radiofrequency interstitial thermal ablation in the treatment of
      small hepatocellular carcinoma.
AB  - PURPOSE: Very few patients affected by hepatocellular carcinoma can undergo
      surgery, though it is considered the only curative therapy. We evaluated
      minimally invasive, percutaneous radiofrequency interstitial thermal ablation for
      treatment of patients with hepatocellular carcinoma who had no surgical
      prospects. PATIENTS AND METHODS: Twenty-four patients (16 men and 8 women; age
      range, 53 to 79 years) with 25 hepatocellular carcinoma nodules of not more than
      3.0-cm diameter underwent radiofrequency interstitial thermal ablation treatment
      with the intent to achieve a cure. In each patient, the thermal necrosis volume
      achieved was about double the tumor volume. RESULTS: At the end of treatment,
      destruction of the tumor was achieved in all but two cases in which further
      thermal lesions were needed. During the mean follow-up interval of 24.8 months
      (range, 6-64), 13 of 24 patients had recurrences, 9 of whom underwent further
      radiofrequency thermal ablation treatment. Radiofrequency thermal ablation was
      again repeated in two patients who showed a second recurrence. A total of 36
      hepatocellular carcinoma nodules in 24 patients were treated. No complications
      were observed. Seven patients died: three due to hepatic failure with advanced
      cancer, three due to heart failure, and one due to pneumonia. Cumulative survival
      curves indicated that the median survival time was 44 months and survival rate
      was 0.95 the first year, 0.84 the second year, 0.67 the third year, and 0.45 the
      fourth and fifth years. CONCLUSIONS: Percutaneous radiofrequency thermal ablation
      can be considered a useful new treatment for small hepatocellular carcinoma in
      patients without surgical prospects. It is simple, effective, and safe, and can
      be repeated in case of recurrence.

PMID- 9166458
TI  - The development of new cancer therapies based on the molecular identification of
      cancer regression antigens.
AB  - Knowledge of the nature of immune reactivity to human tumors has increased
      dramatically in the past decade. Prior to this, there was significant doubt as to
      whether tumor antigens actually existed on growing human cancers, and if so,
      there was considerable skepticism about whether immunotherapies could ever be
      used to affect growing tumors. The development of reproducible techniques for
      generating human lymphocytes with reactivity against tumor antigens, the
      demonstration that the recognition of tumor antigens obeys the same immunologic
      laws of MHC restriction that characterize immunologic reactions against other
      antigens, and the demonstration that T-cell transfer therapies--as well as
      immunotherapies using immune stimulants such as IL-2--could cause the regression
      of established growing cancers in humans have transformed the study of human
      tumor immunology from a speculative science to one with concrete applications to
      the treatment of patients with cancer. The cloning of the genes encoding cancer
      antigens and the molecular identification of the encoded proteins has opened new
      possibilities for the development of cancer treatments. Although several human
      cancer antigens have been identified, only a small number of histologic types of
      tumors have been studied and these investigations need to be extended to identify
      putative tumor antigens expressed on common epithelial neoplasms. There is
      considerable uncertainty surrounding the mechanism by which immune reactions to
      these cancer antigens are generated in humans. Thus far, all of the cancer
      rejection antigens recognized by TIL, as well as additional antigens described by
      others, represent antigens that are encoded by normal nonmutated genes that are
      expressed on selected normal tissues as well as on tumors. An understanding of
      the mechanisms by which the tumor can break tolerance to these normal antigens
      represents a significant challenge to immunologic studies, the answer to which
      may provide additional insight into methods for enhancing antitumor immune
      responses.

PMID- 9166459
TI  - Using clinical trial information in the practice of medicine.

PMID- 9166460
TI  - Palliation of regional symptoms of advanced extremity melanoma by isolated limb
      perfusion.

PMID- 9166461
TI  - Tumor angiogenesis in women with node-positive breast cancer.

PMID- 9166462
TI  - Dose escalation with three-dimensional conformal radiotherapy.

PMID- 9166463
TI  - Iododeoxyuridine radiosensitization of human glioblastoma cells.

PMID- 9166464
TI  - Adjuvant chemotherapy for premenopausal breast cancer: a meta-analysis using
      quality-adjusted survival.
AB  - PURPOSE: Adjuvant chemotherapy for early breast cancer has been shown to offer an
      improvement in recurrence-free and overall survival, especially for younger
      women, but the acute toxic effects of this treatment discourage some physicians
      from prescribing it. The purpose of this analysis was to determine whether the
      benefit of 6 months of adjuvant CMF (cyclophosphamide, methotrexate,
      fluorouracil) treatment outweighs its costs in terms of toxic effects. METHODS: A
      meta-analysis of quality-adjusted survival was performed based on data from 1229
      patients, aged 49 years or younger, randomized in eight trials comparing CMF
      versus no adjuvant systemic therapy. The eight trials were included in the
      worldwide overview conducted by the Early Breast Cancer Trialists' Collaborative
      Group. The Q-TWiST method was used in a meta-analysis that provided treatment
      comparisons incorporating differences in quality of life associated with the
      amount of time patients spend with subjective toxic effects, after relapse, and
      without symptoms of relapse. RESULTS: Within 6 years of follow-up evaluation for
      patients with node-positive disease, the benefit in terms of increased relapse
      free and overall survival balanced the costs in terms of acute toxic side
      effects. This was true even for the extreme case in which a zero value was
      assigned to all 6 months during which patients might receive adjuvant CMF
      chemotherapy. Within 10 years of follow-up evaluation, treated patients gained an
      average of 1.5 years of relapse-free survival time, almost 1 year of overall
      survival time, and 1 year of time without symptoms and toxicity. CONCLUSIONS:
      Adjuvant chemotherapy for younger women with node-positive breast cancer provided
      substantial amounts of quality-adjusted survival time, even after accounting for
      costs associated with toxic effects of the treatment. The Q-TWiST method
      represents a valuable tool for comparing treatments because it incorporates
      patients' perceptions of their quality of life for therapeutic decision-making.

PMID- 9166465
TI  - Palliation of regional symptoms of advanced extremity melanoma by isolated limb
      perfusion with melphalan and high-dose tumor necrosis factor.
AB  - PURPOSE: Bulky, symptomatic melanoma of the extremity is a difficult management
      problem. In some patients, slowly progressive yet extensive regional disease can
      produce pain, edema, bleeding, and immobility. The use of hyperthermic isolated
      limb perfusion may provide good regional palliation even in the presence of
      distant metastatic disease. This study evaluates the ability of isolated limb
      perfusion using melphalan and high-dose tumor necrosis factor to palliate
      regional symptoms of locally advanced extremity melanoma. METHODS: Fifteen
      patients with symptomatic extremity melanoma were treated for 90 minutes with
      isolated limb perfusion using mild hyperthermia, tumor necrosis factor at a dose
      of 4 mg (n = 8) or 6 mg (n = 7) given at the initiation of perfusion, and
      melphalan, 10 mg/L limb volume, given at 30 minutes into the perfusion. Eleven
      patients also received three courses of low-dose gamma-interferon, 0.2 mg
      subcutaneously, once a day for the 2 days preceding surgery and at the initiation
      of perfusion. RESULTS: Symptomatic improvement was achieved in 9 of 11 patients
      who had pain, 6 of 6 patients with edema, 5 of 6 patients with decreased
      extremity mobility, and 5 of 6 with bleeding or severe ulceration. The objective
      response rate in 14 evaluable patients was 100%, with a complete response rate in
      5 of 14. Twelve of 15 patients achieved local control of advanced extremity
      melanoma after isolated limb perfusion. Treatment-related systemic toxicities
      were minimal and short lived. CONCLUSIONS: Isolated limb perfusion with melphalan
      and tumor necrosis factor is an effective and safe palliative treatment of
      locally advanced symptomatic melanoma of the extremity.

PMID- 9166466
TI  - Tumor angiogenesis predicts clinical outcome of node-positive breast cancer
      patients treated with adjuvant hormone therapy or chemotherapy.
AB  - PURPOSE: Experimental studies suggest that angiogenesis is necessary for breast
      cancer progression and metastasis and that it may play a role in responsiveness
      to some chemotherapeutic agents and to tamoxifen. To investigate whether
      angiogenesis predicts the clinical outcome of patients with node-positive breast
      cancer, we determined intratumoral microvessel density in a series of patients
      treated with either adjuvant hormone therapy (n=84) or chemotherapy (n= 107).
      PATIENTS AND METHODS: We monitored 191 patients for a median of 62 months.
      Intratumoral microvessel density was measured using light microscopy, and
      microvessels were immunostained using the anti-CD31 antibody. Microvessels were
      carefully counted (per 200x field) in the most vascularized area of each tumor.
      The results of intratumoral microvessel density were analyzed by both univariate
      and multivariate statistical analysis and were correlated with clinical outcome.
      RESULTS: In univariate analysis, intratumoral microvessel density was
      significantly associated with relapse-free survival and overall survival, both in
      patients who received adjuvant hormone therapy and those who received
      chemotherapy. In the group treated with adjuvant hormone therapy, estrogen
      receptor status was also predictive for both relapse-free and overall survival.
      The number of involved nodes was predictive for overall survival. In patients
      treated with adjuvant chemotherapy, the number of involved nodes, tumor size, and
      progesterone receptor status were significantly predictive for relapse-free and
      overall survival. Multivariate analysis showed that intratumoral microvessel
      density was the strongest independent predictor of outcome in both treatment
      groups. CONCLUSIONS: Intratumoral microvessel density is an independent
      predictive indicator in node-positive breast cancer patients treated with either
      adjuvant chemotherapy or adjuvant hormone therapy. Assessment of tumor
      angiogenesis may therefore be useful in selection of those patients who are more
      likely to benefit from conventional adjuvant therapies (i.e., those with
      minimally vascularized tumors) from those with highly vascularized and more
      aggressive tumors, for whom novel forms of systemic therapy are advocated.

PMID- 9166467
TI  - The feasibility of dose escalation with three-dimensional conformal radiotherapy
      in patients with prostatic carcinoma.
AB  - PURPOSE: To evaluate the acute morbidity, late toxicity, and response to
      treatment in patients with prostate cancer treated on a phase I dose-escalation
      study with three-dimensional conformal radiotherapy. METHODS: A group of 432
      patients with stages T1c-T3 prostate cancer were treated with three-dimensional
      conformal radiotherapy targeting the prostate and seminal vesicles, but
      effectively excluding the surrounding normal tissue structures from the high-dose
      volume. A minimum tumor dose of 64.8 to 66.6 Gy was given to 89 patients (20%),
      70.2 Gy to 199 patients (46%), 75.6 Gy to 98 patients (23%), and 81.0 Gy to 46
      patients (11%). RESULTS: Treatment was well tolerated, and the acute toxicities
      and long-term complications observed were of minimal severity (grade 1 or 2)
      regardless of dose. Acute grade 2 rectal symptoms were observed in 15% of
      patients, whereas 40% developed grade 2 urinary symptoms. Among patients who
      received from 64.8 to 70.2 Gy, the 2-year actuarial likelihood of grade 2 late
      toxicity was 2% for rectal and 1% for urinary complications, compared to 11% and
      5%, respectively, for those treated with doses ranging from 75.6 to 81 Gy. Only
      three patients (0.7%) have so far developed severe (grade 3 or 4) late urethral
      or rectal complications. The rate of prostate-specific antigen normalization from
      abnormal pretreatment levels to a value of < or = 1.0 ng/mL was used as an
      endpoint to evaluate the initial response to treatment. When the analysis was
      restricted to patients with pretreatment prostate-specific antigen levels of < or
      = 20 ng/mL, patients who received 70.2 Gy had a significantly higher rate of
      prostate-specific antigen normalization than patients who received 64.8 to 66.6
      Gy. Evaluation of the prostate-specific antigen response at 75.6 Gy and 81.0 Gy
      was not possible because of the short follow-up time in many of these patients.
      CONCLUSIONS: Three-dimensional conformal radiotherapy technique has made it
      possible safely to escalate radiation doses to unprecedented levels in patients
      with prostatic cancer. Preliminary evidence for an improved initial prostate
      specific antigen response with higher doses indicates a potential for an improved
      therapeutic ratio with the three-dimensional conformal radiotherapy approach.

PMID- 9166468
TI  - Iododeoxyuridine radiosensitization of human glioblastoma cells exposed to acute
      and chronic gamma irradiation: mechanistic implications and clinical relevance.
AB  - PURPOSE: Iododeoxyuridine (IdUrd) is a recognized sensitizer of sparsely and some
      densely ionizing radiations. The mechanism of sensitization remains uncertain.
      Sensitization is likely to involve increased production of DNA damage and/or
      inhibition of DNA damage repair. To test these possibilities, we have
      characterized acute and chronic radiosensitization, and the sublethal damage
      repair capacity of two human glioblastoma cell lines, with or without clinically
      relevant concentrations of IdUrd. MATERIALS AND METHODS: Exponentially growing
      human glioblastoma cell lines, G18 and U251, were irradiated with acute (1.4
      Gy/min) and chronic (20, 40, and 80 cGy/hr) cobalt 60 exposures in the presence
      and absence of 0 to 10 microM IdUrd. Clonogenic survival was determined.
      Sensitizer enhancement ratios and global survival curve comparisons were
      determined with and without IdUrd. Repair half-times for chronic exposures with
      and without IdUrd were calculated. Split-dose recovery following acute fractions
      of 5 Gy separated by 0, 0.5, 1, 2, and 5 hours was evaluated. RESULTS: Following
      acute exposure, a sensitizer enhancement ratio at 10% survival of 1.85 and 1.75
      was observed at concentrations of 10 microM IdUrd for the G18 and U251 cell
      lines, respectively. A global comparison of the survival curves similarly
      revealed significant sensitization at 10 microM IdUrd. Sensitizer enhancement
      ratios and global comparisons of the chronic exposures showed significant
      sensitization in the presence of 2 microM IdUrd for both lines. No significant
      interaction between dose rate and IdUrd effect could be shown using a global
      comparison. Repair half-times for chronic exposures were similar in the presence
      or absence of IdUrd. Both cell lines demonstrate capacity for sublethal damage
      repair in the presence of 2 microM IdUrd in split-dose experiments. CONCLUSION:
      The results of the chronic clonogenic and split-dose studies suggest that
      increased DNA damage production contributes to the mechanism of IdUrd radio
      sensitization, perhaps more so than repair inhibition. A capacity for sublethal
      damage repair is not necessarily a prerequisite for sensitization. IdUrd remains
      an attractive sensitizer of ionizing irradiation delivered at high or low dose
      rates, particularly for actively growing tumors located in quiescent normal
      tissues.

PMID- 9166469
TI  - Cytolytic T-cell clones define HLA-A2-restricted human cutaneous melanoma peptide
      epitopes: correlation with T-cell receptor usage.
AB  - PURPOSE: We studied the T-cell receptor alpha chain and beta chain variable
      region usage in HLA-A2-restricted and melanoma-specific T lymphocytes and
      correlated such T-cell receptor usage with HLA-A2-presented peptide-specific T
      cell recognition. MATERIALS AND METHODS: Tumor-infiltrating lymphocytes were
      isolated from a metastatic melanoma lesion and cloned by limiting dilution.
      Clonal and oligoclonal tumor-infiltrating lymphocytes were analyzed for major
      histocompatibility complex class I--presented melanoma peptide recognition by
      using acid-eluted and high-performance liquid chromatography--fractionated
      melanoma peptides presented by HLA-A2 as targets. The T-cell receptor variable
      regions of the alpha and beta chains of each individual T-cell clone or
      oligoclonal T-cell population were analyzed by mRNA extraction and reverse
      transcribed cDNA by polymerase chain reaction using a panel of T-cell receptor
      alpha and beta variable region specific primers. RESULTS: We demonstrated that
      individual T-cell clones are capable of recognizing peptides within multiple high
      performance liquid chromatography fractions containing melanoma epitopes, and
      that individual high-performance liquid chromatography fractions containing
      melanoma epitopes can be recognized by T-cell clones exhibiting limited usage of
      the T-cell receptor alpha and beta variable region chains. DISCUSSION: These
      results confirm the heterogeneity of T-cell-defined melanoma antigens in a single
      individual and suggest the possibility of developing novel antimelanoma
      therapeutic reagents using either peptides (as immunogens) or the T-cell
      receptors themselves (as gene therapy when introduced into lymphoid effectors).

PMID- 9166470
TI  - Radiation oncology and the new biology.

PMID- 9166471
TI  - VHL gene mutation and clear-cell renal carcinomas.

PMID- 9166472
TI  - Tamoxifen, uridine transport, and dome formation in human breast cancer cells.

PMID- 9166473
TI  - The standard to come: systemic therapies for systemic disease.

PMID- 9166474
TI  - Breast cancer screening between ages 40 and 49.

PMID- 9166475
TI  - Mechanism of tumorigenesis of renal carcinomas associated with the constitutional
      chromosome 3;8 translocation.
AB  - PURPOSE: Members of a family carrying a constitutional balanced translocation
      [t(3;8) (p14;q24)] have a high risk of developing multiple, bilateral clear-cell
      renal carcinomas. Two genetic mechanisms of carcinogenesis for this malignancy
      have been proposed: (1) disruption of a gene at the translocation breakpoint and
      (2) mutation of the von Hippel-Lindau tumor-suppressor gene at 3p25. This study
      further evaluates the role of the von Hippel-Lindau gene in the etiology and
      pathogenesis of t(3;8)-associated renal carcinomas. METHODS: Two new t(3;8)
      associated renal carcinomas were tested for mutations in the von Hippel-Lindau
      gene by single-stranded conformational polymorphism analysis followed by direct
      DNA sequencing, for loss of alleles on chromosomes 3p and 8, and for methylation
      abnormalities in the first cloned exon of the von Hippel-Lindau gene. RESULTS: A
      missense mutation in the von Hippel-Lindau gene was found in one of the two
      t(3;8)-associated renal carcinomas. This mutation would produce a stop codon and
      a truncated protein. Both tumors showed a loss of alleles on the derivative 8
      chromosome. When these results were combined with the results of our previous
      studies, two of the four t(3;8)-associated renal carcinomas, which were examined
      for molecular genetic changes, showed different von Hippel-Lindau somatic
      mutations. All renal tumors from the 3;8 translocation family showed loss of the
      translocated portion of chromosome 3. CONCLUSIONS: These results support a
      mechanism of tumorigenesis in the chromosome (3;8) translocation family that
      involves the loss of both copies of the von Hippel-Lindau gene.

PMID- 9166476
TI  - High CD44 expression on human mesotheliomas mediates association with hyaluronan.
AB  - PURPOSE: Malignant pleural mesothelioma is a rare malignancy with major
      environmental implications regarding passive asbestos exposure. We have conducted
      an immunohistochemical and functional study to address three questions: (1) What
      is the representation of CD44 on tumor cells as detected by immunohistochemistry?
      (2) Do cultured cell lines derived from malignant pleural mesothelioma tissue
      express the same CD44 phenotypes as the original tumors, and can they serve as a
      model for the study of CD44 in mesotheliomas? (3) What is the functional status
      of the CD44 expressed on mesotheliomas, with regard to hyaluronan anchorage?
      MATERIALS AND METHODS: Thirty-seven samples of pleural mesothelioma were obtained
      from patients entered on phase I/II protocols conducted in the Surgery Branch of
      the National Cancer Institute since 1991. The diagnosis was confirmed in all 37
      patients by means of a battery of immunohistochemical tests for markers
      differentiating malignant pleural mesothelioma from adenocarcinoma. Tumor
      positive lymph nodes and distant metastases were also examined in six of the
      patients. Cell lines, established from tumor tissue of six of the patients
      described above, were used in these experiments. Four (H2596, H2461, H2373,
      H2452) were derived from primary solid tumors and two (HP-1 and HP-3) were
      derived from effusions. RESULTS: Immunohistochemical staining with a monoclonal
      antibody (H4C4) that recognizes a constant region of human CD44 demonstrated that
      34 (92%) of the malignant pleural mesotheliomas examined expressed CD44 on 50% to
      100% of their cells. The extent of CD44 expression was apparently related to
      histologic subtype with the highest expression seen in epithelioid mesotheliomas
      and the least in sarcomatoid tumors. Tumor cell lines established from the
      primary tumors or effusions of six of the malignant pleural mesothelioma patients
      showed high expression of the hematopoietic form of CD44. Four of these cell
      lines exhibited strong attachment to hyaluronan in an in vitro attachment assay,
      indicating that their CD44 was functional with respect to hyaluronan anchorage.
      Hyaluronan attachment was specific in that it could be abolished by preincubation
      with epitope-specific anti-CD44 antibodies or soluble substrate or by
      hyaluronidase treatment of attachment surfaces. CONCLUSIONS: We conclude that
      CD44 is highly expressed on human mesotheliomas, that cell lines adequately
      represent tumor expression, and that CD44 mediates association with hyaluronan, a
      major component of pleural fluid.

PMID- 9166477
TI  - Phase I dose-escalation study of tumor necrosis factor-alpha and concomitant
      radiation therapy.
AB  - PURPOSE: Tumor necrosis factor-alpha enhances x-ray killing of human tumor cells
      in vitro and enhances tumor control when combined with radiation in animal tumor
      models. To determine the toxicity and maximal tolerated dose of tumor necrosis
      factor-alpha given daily during radiotherapy, we conducted a phase I dose
      escalation study combining tumor necrosis factor-alpha and radiation. PATIENTS
      AND METHODS: Thirty-one patients, including 14 patients with locally advanced
      primary tumors and 17 patients with metastatic sites, were entered into this
      study. Recombinant human tumor necrosis factor-alpha was administered
      intravenously at doses ranging from 10 microg/m2 to 150 microg/m2 4 hours prior
      to each radiation therapy session, which was given on consecutive days for a
      minimum of 2 weeks. Radiation was prescribed to localized fields, with dose
      fractions ranging from 150 to 300 cGy/day for palliation or control of locally
      advanced tumors. RESULTS: Major toxicity requiring withdrawal from the study was
      independent of tumor necrosis factor-alpha dose and occurred in seven patients.
      Symptoms included angina in two patients, and hypotension, respiratory distress,
      atrial fibrillation, allergic reaction, and progressive leukopenia in one patient
      each. A tumor necrosis factor-alpha dose of 150 microg/m2 was the maximum dose
      administered. No single dose-limiting toxicity was observed and a maximal
      tolerated dose could not be defined. There was no obvious increase in in-field
      toxicity. Response to treatment was assessed in 20 patients. Complete regression
      within the irradiated field was achieved in four patients, partial regression in
      four, and a minimal response in four. A trend toward a greater response rate at
      higher doses of tumor necrosis factor-alpha was observed. CONCLUSIONS: The
      maximal tolerated dose of tumor necrosis factor-alpha when given with
      radiotherapy is at least 150 microg/m2 and a dose-limiting toxicity was not
      observed. Future studies will show whether responses to treatment are increased
      over those expected with radiation alone. Tumor localization of tumor necrosis
      factor-alpha by gene therapy combined with radiation therapy may eliminate the
      systemic toxicity we observed.

PMID- 9166478
TI  - Tamoxifen induces Na+ -dependent uridine transport and dome formation in a human
      breast tumor cell line.
AB  - PURPOSE: To correlate changes in uridine transport and colony morphology with
      differentiation of human breast cancer cells by tamoxifen and related agents.
      MATERIALS AND METHODS: Cultures of MCF-7 human breast cancer were treated with
      estradiol or the antiestrogen derivatives tamoxifen, hydroxytamoxifen, and ICI
      164, 384. Initial rates of uridine transport and equilibrium concentrations were
      determined and morphological characteristics of the cultures evaluated. RESULTS:
      Tamoxifen causes an early induction of a Na+ -dependent transport of uridine
      characteristic of normal epithelial cells but absent in normal MCF-7 cultures and
      most human neoplasms examined. The pure antiestrogen ICI 164,384 and the more
      potent 4-hydroxytamoxifen also induced concentrative uridine transport; estradiol
      could prevent the expression of this transporter. Associated with induction of
      transport was a dramatic increase in dome formation in the cultures, a measure of
      unidirectional inorganic ion transport characteristic of the differentiated
      state. CONCLUSIONS: The induction of a concentrative transport of uridine is a
      concomitant of cellular differentiation of breast tumor cells. These findings
      give added weight to evidence that uridine may play a regulatory role in the
      transition to the neoplastic state. The absence of the transporter and low
      intracellular uridine concentrations in the undifferentiated state may relate to
      5-FU sensitivity of breast tumors. Induction of the transporter by tamoxifen and
      the consequent major increase in intracellular concentrations of free uridine
      suggests a potentially negative effect of tamoxifen on regimens containing 5-FU.

PMID- 9166479
TI  - Influence of treatment sequence on efficacy of fluorouracil and cisplatin
      intratumoral drug delivery in vivo.
AB  - PURPOSE: The influence of treatment sequence in combination chemotherapy using
      fluorouracil (5-FU) and cisplatin (CDDP) was investigated in a mouse tumor model.
      Both drugs were formulated as therapeutic injectable gels, 5-FU/epinephrine gel
      and CDDP/epinephrine gel, and used intratumorally in a multiple-treatment
      regimen. By testing various multiple-treatment regimens, we determined optimal
      treatment sequences for these two injectable gels. Then we compared the antitumor
      responses achieved using the optimal treatment sequences for the intratumorally
      administered gels with the responses obtained using 5-FU and CDDP solutions
      administered intratumorally or systemically in the same treatment sequence.
      MATERIALS AND METHODS: Tumor-bearing C3H mice received a total of four injections
      (every 2 to 3 days from day 0 through day 7) of 5-FU solution, CDDP solution, 5
      FU/epinephrine gel, or CDDP/epinephrine gel either as single agents or in various
      combinations and alternate sequences of solutions or gels. The delay in tumor
      growth was used as a study end-point. RESULTS: The results showed that local
      treatment (i.e., intratumoral administration) was more efficacious than systemic
      treatment (i.e., intraperitoneal administration) when both 5-FU solution and CDDP
      solution were used either alone or in combination. Further, using two drugs in
      combination was superior to using either drug alone. When both drugs were
      delivered intratumorally in the injectable gel formulations, the combination
      treatment sequences initiated with 5-FU/epinephrine gel were superior to
      sequences initiated with CDDP/epinephrine gel in delaying the tumor growth. The
      two sequences initiated with 5-FU/epinephrine gel (i.e., two treatments with 5
      FU/epinephrine gel followed by two treatments with CDDP/epinephrine gel and the
      sequence of alternating 5-FU/epinephrine gel and CDDP/epinephrine gel) showed no
      significant difference in antitumor efficacy. Both these sequences (initiated
      with 5-FU/epinephrine gel) produced the longest delays in tumor growth, and > or
      = 50% (7 of 12) animals remained disease free at the end of the 60-day study.
      CONCLUSION: These studies demonstrate that significant improvement in local tumor
      control in mice can be achieved with a simple treatment sequence alteration of
      two established drugs.

PMID- 9166480
TI  - Final report of a phase II study of chemotherapy with bleomycin, epirubicin, and
      cisplatin for locally advanced and metastatic/recurrent undifferentiated
      carcinoma of the nasopharyngeal type.
AB  - PURPOSE: This article presents an assessment of the combination of bleomycin,
      epirubicin, and cisplatin as induction chemotherapy before radiotherapy in the
      treatment of undifferentiated carcinoma of the nasopharyngeal type in patients
      with recurrent/metastatic disease (group A), and in previously untreated patients
      with locoregionally advanced disease (UICC-AJCC 87, N2-3, M0) (group B) in terms
      of toxicity, antitumoral activity, and therapeutic efficacy. PATIENTS AND
      METHODS: From January 1987 to September 1990, 111 consecutive patients with
      histologically proven UCNT were treated with six cycles of intravenous cisplatin
      (100 mg/m2 day 1) epirubicin (80 mg/m2 day 1), and bleomycin (15 mg bolus day 1),
      followed by 16 mg/m2/day continuous infusion for 5 days, repeated every 21 days
      for three cycles. Three further cycles without bleomycin were given to 44
      patients in group A. In group B (67 patients), only three cycles of the same
      protocol were given, with a slightly lower dose of epirubicin (70 mg/m2),
      followed by conventional radiotherapy (70 Gy/7 weeks). RESULTS: Of 44 patients
      entered in group A, 38 were evaluable for response. We observed 9 (20%) complete
      responses and 11 (25%) partial responses, for a 45% overall response rate. In 12
      patients not previously given chemotherapy, there were 4 complete responses,
      compared to 5 complete responses in 32 patients previously treated with
      chemotherapy. Four patients are alive with no evidence of disease after 53+, 60+,
      61+, and 72+ months. In group B the overall response rate to chemotherapy was 98%
      with 42 complete (62%) and 24 partial responses (36%). Three months after the end
      of radiotherapy, the overall complete response rate was 94% (63 patients). After
      a median follow-up time of 77 months (range, 53-94), the 4-year overall survival
      and disease-free survival rates for this group are 66% and 60%, respectively. The
      median disease-free survival has not been reached at 90 months. CONCLUSION: The
      results of the BEC combination trial are very encouraging in metastatic and
      recurrrent UCNT, with durable remissions in this poor-prognosis population. The
      results in patients with locally advanced disease have motivated prospective
      phase III testing of the neoadjuvant chemotherapy approach to evaluate its impact
      on locoregionally advanced disease (> or =N2MO UICC-AJCC 87).

PMID- 9166481
TI  - Antisense therapy for cancer.

PMID- 9166482
TI  - Erythropoietin usage in patients with cancer.

PMID- 9166483
TI  - Does adjuvant radiation therapy hold promise for improved outcome in advanced
      Hodgkin's disease?

PMID- 9166484
TI  - Paclitaxel: the long and short of it.

PMID- 9166485
TI  - Recombinant human erythropoietin therapy for anemic cancer patients receiving
      cisplatin chemotherapy.
AB  - PURPOSE: To assess whether the administration of recombinant human erythropoietin
      (r-HuEPO) would increase the hematocrit, reduce the requirement for transfusion,
      and improve the quality of life in anemic cancer patients receiving
      myelosuppressive, cisplatin-based chemotherapy. PATIENTS AND METHODS: One hundred
      thirty-two anemic cancer patients receiving cyclic, cisplatin-containing,
      myelosuppressive chemotherapy were evaluated. Patients received either r-HuEPO
      (150 U/kg) or placebo, subcutaneously, three times a week for 3 months. Responses
      were assessed by measuring changes in hemoglobin/hematocrit, transfusion
      requirement, and quality of life. RESULTS: The mean hematocrit increased by 6.0
      percentage points in the r-HuEPO group versus 1.3 in the placebo group. A
      decrease in transfusion requirement did not reach significance over all 3 months,
      but there was a significant reduction in the percentage of patients transfused in
      the second and third months (27% r-HuEPO vs. 56% placebo) and a trend toward
      reduction in the mean total number of units transfused (1.20 units r-HuEPO vs.
      2.02 units placebo), suggesting a lag of 1 month before r-HuEPO can affect the
      transfusion requirement. Pretreatment serum erythropoietin levels were lower in
      responders than in nonresponders (73.5 IU/L and 86.3 IU/L means, respectively).
      However, the magnitude of this difference was not helpful in defining which
      patients were likely to respond. There was a significant improvement in overall
      quality of life between the two treatment arms in favor of the r-HuEPO-treated
      group. There were no significant adverse effects associated with r-HuEPO.
      CONCLUSIONS: r-HuEPO is safe and can cause a significant improvement in the
      hematocrit and quality of life of anemic cancer patients receiving
      myelosuppressive, cisplatin-based chemotherapy. After 1 month of r-HuEPO, there
      is also a reduction in transfusion requirement.

PMID- 9166486
TI  - Recombinant human erythropoietin and platinum-based chemotherapy in advanced
      ovarian cancer.
AB  - PURPOSE: Patients with ovarian cancer often experience dose-limiting
      myelotoxicity, nephrotoxicity and anemia following treatment with platinum-based
      chemotherapy. PATIENTS AND METHODS: To investigate the ability of recombinant
      human erythropoietin (epoetin alfa) to prevent the development of anemia, 30
      patients with advanced ovarian carcinoma receiving cisplatin or carboplatin were
      randomly assigned to treatment with subcutaneous epoetin alfa 300 IU/kg three
      times a week in addition to conventional supportive treatment, or conventional
      supportive treatment alone, for up to six chemotherapy cycles. The dose of
      epoetin alfa was reduced if hemoglobin concentration exceeded 15 g/dL. RESULTS: A
      highly significant difference in mean hemoglobin concentrations was observed
      between the two groups during the first cycle of chemotherapy due to a
      significant decrease in mean hemoglobin concentration in the control group. A
      maximal difference of 3.4 g/dL was achieved during cycle three. Fewer patients
      required blood or platelet transfusions in the epoetin alfa-treated group,
      although the difference was not significant compared to the control group.
      Epoetin alfa was well tolerated. CONCLUSION: Epoetin alfa appears to be effective
      and well tolerated in preventing hemoglobin decline in patients undergoing
      aggressive cyclic platinum-based chemotherapy for advanced ovarian carcinoma.

PMID- 9166487
TI  - Combined modality therapy in previously untreated patients with advanced
      Hodgkin's disease: A 24-year follow-up study.
AB  - PURPOSE: To describe the long-term results of treatment with chemotherapy plus
      adjuvant low-dose, involved-field radiation therapy (CMT) in patients with
      advanced Hodgkin's disease. Data on disease-free and failure-free survival,
      second malignancies, and the results of salvage therapy are presented. PATIENTS
      AND METHODS: From 1969 to 1989, CMT was administered to 186 patients with
      previously untreated stage IIB, III, and IV Hodgkin's disease. Chemotherapy
      included MVVPP (47%), MOPP (25%), MOPP/ABVD (26%) and ABVD (2%). After 6 months
      of chemotherapy, patients received radiation to all involved sites with the
      exception of the bone marrow. RESULTS: The failure-free survival for all patients
      was 63% at 5 years, 56% at 10 years, and 40% at 23.5 years, respectively.
      Significantly worse results were observed in patients older than 40 years and
      those with stage IV disease. The overall survival of 45 patients after recurrence
      was 39% at 10 years, but was only 21% if the initial complete remission lasted
      less than 1 year. Thus far, 21 of 165 patients (12.7%) who achieved complete
      remission have developed a second malignancy, and 16 have died. CONCLUSIONS: In
      comparison with comparable chemotherapy programs, chemotherapy plus radiation
      therapy may improve disease-free survival; however, the results of treatment in
      patients older than age 40 or with stage IV disease are still poor. Although
      patients with initial remissions lasting longer than 1 year can have durable
      second remissions, the long-term disease-free survival is poor and in the current
      series the majority of failures were due to recurrent Hodgkin's disease.

PMID- 9166488
TI  - Hyperthermic isolated limb perfusion with tumor necrosis factor alone for
      melanoma.
AB  - PURPOSE: Recent reports indicate that hyperthermic isolated limb perfusion using
      tumor necrosis factor, interferon gamma and melphalan is associated with response
      rates of greater than 90% in patients with in-transit metastatic melanoma. We
      evaluated the toxicity and efficacy of tumor necrosis factor alone administered
      during hyperthermic isolated limb perfusion. PATIENTS AND METHODS: Six patients
      were perfused at 39.7 degrees to 40 degrees C for 60 to 90 minutes with tumor
      necrosis factor: three patients at a total dose of 1 mg, 2 mg, and 3 mg,
      respectively, and three patients at a total dose of 4 mg. Systemic leak was
      monitored using iodine 131-labelled albumin injected into the perfusate. Tumor
      necrosis factor levels were measured by enzyme-linked immunoabsorbent assay in
      plasma samples obtained from the hyperthermic isolated limb perfusion circuit and
      systemic circulation. RESULTS: Peak perfusate tumor necrosis factor levels,
      available in five of six patients, ranged between 2000 and 8500 ng/mL (mean, 4200
      +/- 2104 ng/mL). Peak systemic tumor necrosis factor levels in three patients
      without evidence of systemic leak ranged between 0.02 and 0.7 ng/mL (mean, 0.22
      +/- 0.24 ng/mL). The first two patients with mean systemic tumor necrosis factor
      levels of 35.6 +/- 14.5 ng/mL exhibited moderate to severe hypotension with
      transient renal insufficiency. Only fever and chills were noted in patients where
      systemic leakwas negligible. Partial response of less than 1 month's duration was
      seen in two patients and no response was noted in three. One patient had a
      complete response of 7 months' duration and then progressed. Three patients have
      been reperfused with triple drug hyperthermic isolated limb perfusion (two
      complete responses and one partial response). CONCLUSIONS: In light of the
      impressive results of triple drug hyperthermic isolated limb perfusion, it
      appears that hyperthermic isolated limb perfusion with tumor necrosis factor
      alone has inadequate activity to warrant further investigation. The relative
      contribution of tumor necrosis factor and interferon gamma to melphalan requires
      further study.

PMID- 9166489
TI  - Paclitaxel administered by a 1-hour infusion: A phase I-II trial comparing two
      schedules.
AB  - PURPOSE: Paclitaxel is currently administered by prolonged intravenous infusion
      primarily because of severe hypersensitivity reactions that occurred with rapid
      infusions during early clinical trails. This phase I-II study evaluates the
      feasibility of 1-hour paclitaxel administration and compares the toxicity and
      efficacy of two different 1-hour infusion schedules. PATIENTS AND METHODS: One
      hundred sixty-four patients with advanced, refractory cancer were randomized to
      receive one of two paclitaxel schedules: a 1-hour infusion or a 3-day, divided
      dose schedule, each daily dose administered by 1-hour infusion. The first 60
      patients received a total paclitaxel dose of 135 mg/m2, and the remaining 104
      patients received 200 mg/m2. All patients were premedicated with dexamethasone,
      diphenhydramine, and cimetidine. Cytokines were not routinely used. RESULTS: No
      serious hypersensitivity reactions occurred in 620 courses of paclitaxel. Both
      doses were well tolerated; grade 3 or 4 leukopenia was produced in 22% of courses
      at 135 mg/m2 and 23% of courses at 200 mg/m2. Both schedules were well tolerated,
      but grade 3 and 4 leukopenia was more common with the 3-day schedule when
      paclitaxel 200 mg/m2 was administered. Myalagias were more common with the 1-day
      schedule. Major responses occurred in 35 of 153 evaluable patients (23%).
      Response rates in ovarian, breast, and non-small cell lung cancer were 45%, 33%,
      and 25%, respectively. At the 200 mg/m2 dose, 11 of 36 patients (31%) with non
      small cell lung cancer responded, including 6 of 16 who had received previous
      chemotherapy. No major difference in response rates was observed when the 1-day
      and 3-day schedules were compared. CONCLUSIONS: Paclitaxel can be safely
      administered by 1-hour infusion in an outpatient setting. A dose of 200 mg/m2 is
      well tolerated without the use of cytokines. Both schedules are well tolerated;
      however, the 3-day schedule produces more leukopenia when a 200 mg/m2 dose is
      administered. Antitumor activity was seen with both doses and schedules.
      Administration of paclitaxel over 1-hour is less toxic, easier, and less
      expensive than are prolonged infusions, and deserves continued investigation.

PMID- 9166490
TI  - A phase I-phase II study of vinorelbine with cisplatin, 5-fluorouracil, and
      leucovorin for advanced non-small cell lung cancer.
AB  - PURPOSE: The combination of cisplatin, 5-fluorouracil, and leucovorin (PFL) has
      been reported to have a 29% response rate in advanced non-small cell lung cancer.
      Vinorelbine, a semi-synthetic vinca alkaloid, has also been reported to have
      single-agent activity in this disease. We designed a phase I-II study in which
      escalating doses of vinorelbine were added to PFL to define the dose-limiting
      toxicity and maximum tolerated dose of vinorelbine, and to determine the response
      rate and survival at the recommended phase II dose. PATIENTS AND METHODS: This
      study enrolled patients between December 1991 and August 1993. Eligibility
      criteria included histologically or cytologically documented stage III or IV non
      small cell lung cancer, measurable or evaluable disease, and no prior
      chemotherapy. Treatment consisted of escalating doses of vinorelbine (starting at
      20 mg/m2) on days 1 and 6, cisplatin 100 mg/m2 on day 2, and 5-fluorouracil as a
      continuous infusion at 800 mg/m2/day for 4 days (days 2-5) with leucovorin 100 mg
      orally every 4 hours on days 1 through 5. Cycles were repeated every 21 days.
      RESULTS: Forty patients were treated during the study. The median age of the
      patients was 58 (range, 33-75) and 36 patients had a performance status of 0 or
      1. Dose-limiting neutropenia was observed in both patients treated with
      vinorelbine at 25 mg/m2. At the recommended phase II vinorelbine dose of 20 mg/m2
      on days 1 and 6, myelosuppression remained the most common toxicity, with 22
      patients (55%) having grade 4 neutropenia. Fifteen patients (38%) required
      hospital admission for neutropenic fever; two died of neutropenic sepsis. Of 33
      patients evaluated, 2 patients achieved a complete response and 10 patients
      achieved a partial response (overall response rate, 30%; 36% of the evaluated
      patients). Median survival was 10.4 months for the entire cohort (16.4 months for
      those with stage III disease and 9.6 months for patients with stage IV disease)
      and 1-year survival was 45%. The overall median time to progression was 8.1
      months. CONCLUSIONS: The maximum tolerated dose of vinorelbine given on days 1
      and 6 with PFL is 20 mg/m2; myelosuppression is the dose-limited factor. The
      response rate is similar to rates observed in prior studies of combination
      chemotherapy, but the median survival of patients with stage IV disease exceeds
      that of many other regimens.

PMID- 9166491
TI  - The Revlon/UCLA Breast Center Practice Guidelines for the Treatment of Breast
      Disease.

PMID- 9166492
TI  - Recombinant anticancer vaccines.

PMID- 9166493
TI  - Does the sequence of radiotherapy and chemotherapy in breast-conserving therapy
      influence outcome?

PMID- 9166494
TI  - In vivo murine tumor gene delivery and expression by systemic recombinant
      vaccinia virus encoding interleukin-1beta.
AB  - PURPOSE: This study investigates the feasibility of systemic gene delivery in a
      tumor-bearing host using a vaccinia virus-based in vivo gene delivery and
      expression system. METHODS: A recombinant vaccinia virus encoding human
      interleukin-1beta (hIL-1beta) was constructed with a strong synthetic vaccinia
      virus late promoter driving hIL-1beta gene expression. C57BL/6 mice bearing
      established subcutaneous pancreatic tumors were injected intravenously in a
      blinded, randomized fashion with different doses of either the recombinant
      vaccinia virus(vMJ601hIL-Ibeta), control vaccinia (wild-type or TK-deficient), or
      saline. Toxicity was assessed, serial tumor sizes were measured, and viral titers
      and the amount of hIL-1beta in tumor, liver, and spleen were determined. RESULTS:
      High viral titers (10(6) PFU/g) were detected in tumors for all three viruses on
      postinjection day 3, and tumor viral titers persisted at high levels until day 9.
      In contrast, viral titers were initially 104-fold lower in nontumor tissues and
      decreased to undetectable levels by day 9. vMJ60hIL-1beta was rapidly cleared
      from liver and spleen by day 3 (titer levels < 100 PFU/g), while tumor titer
      levels persisted at 8.5 x 10(6) PFU/g. hIL-1beta was measurable in three of three
      tumors from vMJ601hIL-1beta treated mice on postinjection day 3, one of three on
      day 6, and one of three on day 9; no hIL-1beta was detected in any other tumors
      or normal tissues. Wild-type vaccinia had no antitumor effects. Treatment with
      two different doses of vMJ601hIL-1beta resulted in a consistent and significant
      decrease in tumor size in repeatable experiments as compared to controls.
      Histologic analysis revealed tumor cell necrosis with a surrounding neutrophil
      infiltrate in the vMJ601hIL-1beta treated tumor. CONCLUSION: These data show that
      recombinant vaccinia virus encoding hIL-1beta given intravenously preferentially
      localizes and amplifies in tumor tissue, is rapidly cleared from liver and
      spleen, produces measurable hIL-1beta in tumor but not normal tissues, and
      inhibits growth of established solid tumors in mice. Recombinant vaccinia virus
      encoding therapeutic genes may be a practical, efficient vehicle for direct in
      vivo gene transfer and expression in the treatment of cancer.

PMID- 9166495
TI  - Human papillomavirus DNA in tumor-free regional lymph nodes: a potential
      prognostic marker in cervical carcinoma.
AB  - PURPOSE: The medical management of women with cervical carcinoma would benefit
      from a test that might predict which patients have a high risk of progression or
      recurrence. The detection of micrometastases in regional lymph nodes may be such
      a test. At least 90% of cervical carcinomas worldwide contain human
      papillomavirus (HPV) DNA. In a pilot study, we evaluated a polymerase chain
      reaction-based method for the detection of human papillomavirus DNA in archival
      routine sections of regional lymph nodes as a marker of micrometastasis in
      patients with a long-term follow-up period. PATIENTS AND METHODS: We analyzed 134
      archival routine slides of histologically tumor-free lymph nodes derived from 21
      patients with clinically and pathologically determined stage Ib, IIa, and IIb HPV
      16 positive cervical carcinoma. The patients had been selected for good (still
      alive with a follow-up time of at least 5 years) or fatal outcome (dead of
      disease within 3 years). The amount of HPV-16 DNA was estimated by comparison
      with standards. RESULTS: All patients without strongly HPV-positive lymph nodes
      survived. In contrast, 8 of 12 women with strongly HPV-positive lymph nodes died
      of cervical carcinoma. CONCLUSIONS: In patients with cervical cancer, an approach
      based on a PCR test for HPV DNA in tumor-free regional lymph nodes may allow
      early identification of women at high risk for relapse who should receive
      adjuvant treatment.

PMID- 9166496
TI  - Endometrial pathology at dilatation and curettage in breast cancer patients:
      comparison of tamoxifen users and nonusers.
AB  - PURPOSE: We conducted this retrospective study to determine the endometrial
      pathologic findings at the time of dilatation and curettage in breast cancer
      patients on tamoxifen and compare these findings with those from a similar group
      of patients not receiving tamoxifen. METHODS: The pathologic findings from
      endometrial curettings in all breast cancer patients who underwent a dilatation
      and curettage between January 1986 and June 1993 at our institution were
      retrospectively reviewed. Medical records and office charts were reviewed to
      determine the patient age, history, and duration of tamoxifen use, and the
      presence of symptoms (vaginal spotting or bleeding). RESULTS: Two hundred and
      forty breast cancer patients were identified. Seventy-five patients (31%) were
      taking tamoxifen (mean duration, 26 months) at the time of dilatation and
      curettage. Fifty-three of these patients were symptomatic. Twenty-two of the
      patients taking tamoxifen were asymptomatic. One hundred and sixty-five patients
      (69%) were not taking tamoxifen. Of these patients, 109 were symptomatic and 56
      were asymptomatic. In both symptomatic and asymptomatic breast cancer patients,
      there was no difference in the incidence of endometrial polyps, hyperplasia, or
      adenocarcinoma when comparing tamoxifen users with nonusers. CONCLUSION: Short
      term tamoxifen use in breast cancer patients was not found to alter the
      endometrial pathologic findings at the time of dilatation and curettage.

PMID- 9166497
TI  - The impact of the sequence of radiation and chemotherapy on local control after
      breast-conserving surgery.
AB  - PURPOSE: We conducted this study to evaluate the effects of delaying primary
      radiation after adjuvant chemotherapy on local control following breast
      conserving surgery compared with radiation delivered immediately following
      surgery. PATIENTS AND METHODS: This retrospective, nonrandomized study evaluated
      local control in 471 patients treated with breast-conserving surgery and
      radiation from 1980 through 1990. Three patient subsets were studied, identified
      by the sequence of radiation and adjuvant therapy if given. The three subgroups
      were: surgery, radiation, no chemohormonal therapy (332 patients; RT only);
      surgery, all chemotherapy, radiation (53 patients; chemo first); and surgery,
      chemotherapy, radiation, chemotherapy (86 patients; sandwich). Median follow-up
      times ranged from 53 months in the chemo first group to 77 months in the RT only
      group. RESULTS: All three groups had similar local control rates at 3 and 5
      years. At 36 months, the actuarial local control rate achieved by the RT only
      group was 98% (confidence interval: 95%-99%); by the chemo first group, 94% (CI:
      82%-98%); and the sandwich group, 96% (CI: 89%-99%). At 60 months, the local
      control rate for the RT only group was 96% (CI: 93%-98%), the chemo first group,
      86% (CI: 70%-94%) and the sandwich group 95% (CI: 87%-98%). CONCLUSIONS: This
      report demonstrates no significant difference in the local recurrence rate
      following breast-conserving surgery and radiation therapy, whether radiation
      immediately followed the surgery or whether it was delayed by the administration
      of postsurgical adjuvant chemotherapy. These data differ from other reports, and
      suggest that this question remains open, requiring further follow-up that focuses
      not only on local control as an endpoint, but disease-free and overall survival
      as well.

PMID- 9166498
TI  - High-dose cisplatin as neoadjuvant organ-preserving chemotherapy for squamous
      cell carcinoma of the larynx.
AB  - PURPOSE: We conducted this study to evaluate the efficacy and toxicity of
      fractionated high-dose cisplatin as neoadjuvant organ-preserving chemotherapy,
      followed by definitive radiotherapy, for untreated and advanced squamous cell
      carcinoma of the larynx. MATERIALS AND METHODS: From August 1990 to April 1994,
      32 patients bearing previously untreated advanced squamous cell carcinoma of the
      larynx (12 stage III and 20 stage IV) received three courses of high-dose
      cisplatin (100 mg/m2 on day 1 and day 8 every 28 days) before definitive external
      radiation therapy with 65 to 70 Gy (180-200 cGy daily for 6-8 weeks). Twenty
      eight patients were men; median age was 57 years (range, 31-69); and median
      performance status (ECOG) was 1 (0-2). RESULTS: With an average follow-up time of
      18 months (range, 6-47), 30 patients are evaluable for response and 32 for
      toxicity. Responses after three courses of chemotherapy were: complete response,
      18 patients (60%), and partial response, 7 patients (23%), for an overall
      response rate of 83%. Only one patient showed progressive disease. Fifteen
      patients (50%; 12 complete and 3 partial responders) had pathologic complete
      remission. Eighty percent of patients had no evidence of disease after the
      therapeutic program. Median disease-free survival was 24 months, and median
      overall survival was 28 months (range, 6-47). Overall, in 46% of all evaluable
      patients, organ preservation with acceptable function was achieved. Disease-free
      survival and larynx preservation were strongly correlated with pathologic
      complete remission. The average dose intensity received at the end of the third
      course of therapy was 47 mg/m2/week. There were no drug-related deaths. The main
      acute toxicity was grade 2-3 nausea and vomiting in 75% of patients. Two patients
      developed renal impairment after the first course of cisplatin. Ototoxicity
      (grade 2-3) was seen in 43% of patients, and peripheral neuropathy (grade 2-3)
      was observed in 12% of patients. In contrast, myelotoxicity and mucositis were
      mild. CONCLUSION: In conclusion, this strategy with fractionated high-dose
      cisplatin given on an outpatient basis is an attractive approach that produces a
      high rate of complete response and larynx preservation with an advantageous
      toxicity profile.

PMID- 9166500
TI  - Cytotoxic treatments and tumor oxygenation.

PMID- 9166499
TI  - Antiproliferative effect in vitro and antitumor activity in vivo of brefeldin A.
AB  - PURPOSE: An empiric in vitro screen of human tumor cell lines found brefeldin A
      inhibited the growth of immortalized human cell lines, with particular
      sensitivity to brefeldin in a series of immortalized melanoma cell lines and
      nonimmortalized prostate carcinoma explants. Brefeldin A alters the morphology
      and function of the Golgi apparatus, endosomal, and trans-Golgi compartments in
      different cell types. The studies presented here sought to obtain evidence of in
      vivo antitumor activity by brefeldin A. METHODS: Antiproliferative activity was
      studied in prostate carcinoma cells in vitro using cell counts, protein, and
      viable stains. Activity was also studied in vivo against subcutaneous and
      subrenal capsule melanoma models. RESULTS: Protracted exposures in vitro (between
      24 and 72 hours) are necessary to cause persistent growth inhibition of
      immortalized PC3 prostate carcinoma cells. In human melanoma athymic mouse
      xenografts, brefeldin A showed antitumor activity in vivo when given 16 to 64
      mg/kg/injection intraperitoneally q 7 h x 2, daily for 5 days. Activity was also
      observed in the intraperitoneal LOX IMVI (65%-100% increase in life span, with
      17%-50% day 60 survivors); early-stage subcutaneous LOX IMVI and SK-MEL-5 (86%
      100% growth inhibition), and subrenal capsule SK-MEL-5 and M19-MEL models.
      CONCLUSIONS: Brefeldin A possesses noteworthy antitumor activity in vivo and
      antiproliferative effects in vitro in certain cell types. Strategies to allow
      protracted exposure of tumor cells to brefeldin A while preserving a therapeutic
      index are needed to assess the clinical potential of brefeldin A.

PMID- 9166501
TI  - Cytokine gene therapy of cancer.

PMID- 9166502
TI  - Interleukin-2 therapy: a decade of slow but steady progress.

PMID- 9166503
TI  - Concurrent chemoradiation in unresectable stage III non-small cell lung cancer:
      too much pain for no gain.

PMID- 9166504
TI  - Combined modality treatment with selective bladder conservation for invasive
      bladder cancer: long-term tolerance in the female patient.
AB  - PURPOSE: To assess the physical, psychological, social, and organ-specific long
      term treatment sequelae occurring in women with muscle-invading bladder carcinoma
      treated with combined modality therapy that allowed for bladder conservation in
      67% of patients. PATIENTS AND METHODS: Patients with muscle-invading (T2
      4a,Nx,M0) bladder cancer were treated with maximal transurethral resection
      followed by induction chemoradiotherapy (cisplatin x 2 plus 40 Gy pelvic
      irradiation or the same preceded by 2 cycles of methotrexate, cisplatin, and
      vinblastine) between the years 1986 and 1994. Women who had a complete response
      and all those who were not candidates for cystectomy received consolidation
      therapy of additional cisplatin and tumor boost to 64.8 Gy. Women who were
      incomplete responders and those who developed recurrent invasive tumor underwent
      immediate radical cystectomy. Forty-two women were treated with this approach, 21
      of whom (median age, 69 years; median follow-up time, 56 months) were available
      for and underwent a structured interview of treatment and health-related issues
      using a quantitative symptom score. RESULTS: All 21 patients have full urinary
      continence and no dysuria. Nineteen report unchanged or improved bladder capacity
      and function. No patient reported loss of bowel continence. Of the five women who
      were sexually active, two report an increase in intercourse frequency and one
      noted a decrease. There is no decrease in intercourse satisfaction or orgasm, and
      no dyspareunia or vaginal bleeding was noted. Eleven patients reported high
      levels of anxiety related to their bladder cancer before treatment. This was
      significantly reduced or absent in 9 of 11 after treatment. Actuarial overall
      survival for all 42 women was 58% at 5 years. Actuarial overall survival with an
      intact bladder was 47% at 5 years. DISCUSSION: This study shows that overall
      survival is high when chemoradiation and transurethral resection are used in
      potential bladder-sparing protocols for muscle-invading transitional cell
      carcinoma of the bladder in women. Furthermore, 67% of the women, including most
      long-term survivors, retain their bladders. The functional quality of the
      conserved organ, the rectum, and the vagina, as reported by the patients, was
      excellent.

PMID- 9166505
TI  - Efficacy and safety of oral granisetron versus oral prochlorperazine in
      preventing nausea and emesis in patients receiving moderately emetogenic
      chemotherapy.
AB  - PURPOSE: To compare the efficacy and safety of oral granisetron hydrochloride
      tablets with that of oral prochlorperazine sustained-release capsules in
      preventing nausea and emesis induced by moderately emetogenic chemotherapeutic
      agents. PATIENTS AND METHODS: In this multicenter, double-blind, randomized,
      parallel group study, oral granisetron and oral prochlorperazine were compared in
      230 chemotherapy-naive, adult cancer patients who received moderately emetogenic
      chemotherapy. Patients were stratified by gender and randomized to receive either
      1.0 mg oral granisetron HCI twice a day for 7 days, or 10 mg oral
      prochlorperazine sustained-release capsules twice a day for 7 days. The first
      dose was given 1 hour before initiation of chemotherapy and the second dose 12
      hours after the first dose. Patients were evaluated for emetic episodes, extent
      of nausea, and adverse events for 7 days after the start of chemotherapy. Primary
      efficacy parameters were complete response (no emetic episodes, no greater than
      mild nausea, no antiemetic rescue) and total control (no emetic episodes, no
      nausea, no antiemetic rescue) in the 24 hours after the start of chemotherapy.
      RESULTS: Granisetron was significantly more effective than prochlorperazine in
      achieving a complete response (74% vs. 41%, respectively) and total control of
      nausea and vomiting (58% vs. 33%, respectively) at the 24-hour assessment.
      Complete response at 24 hours was significantly higher in the granisetron-treated
      patients than in prochlorperazine-treated patients. In women, granisetron showed
      a complete response rate of 69% versus 38% with prochlorperazine; in men,
      granisetron showed a complete response rate of 92% versus 61% with
      prochlorperazine. Both regimens were well tolerated, with headache (36% for
      granisetron, 29% for prochlorperazine) and constipation (31% for granisetron, 6%
      for prochlorperazine) the most common adverse events. CONCLUSIONS: : Oral
      granisetron 1 mg twice a day was significantly more effective than oral
      prochlorperazine sustained release capsules 10 mg twice a day in complete
      response and total control of nausea and vomiting at 24 hours after chemotherapy.
      Both agents were well tolerated.

PMID- 9166506
TI  - Correlates of response to IL-2 therapy in patients treated for metastatic renal
      cancer and melanoma.
AB  - PURPOSE: We evaluated the characteristics of patients with metastatic renal
      cancer or metastatic melanoma prior to and during treatment with bolus
      intravenous interleukin-2 to define prognostic indicators of subsequent response
      to therapy. PATIENTS AND METHODS: A consecutive series of 509 patients with
      progressive metastatic cancer were treated with intravenous interleukin-2 from
      September 1985 to July 1993. Pretreatment demographic characteristics, treatment
      history, results of laboratory tests, and metastatic sites of disease were
      evaluated. The amount of interleukin-2 administered, toxicity, and changes in
      laboratory test results were recorded for the first course of therapy. Subsequent
      objective response to therapy and survival were determined and used to evaluate
      pretreatment and treatment characteristics that acted as prognostic indicators of
      response. RESULTS: At the end of the study, 22.6% of patients with renal cancer
      and 16.3% of patients with melanoma experienced an objective response to
      interleukin-2 therapy. Patients with renal cancer responded more frequently if
      they had not previously failed other immunotherapies. Also, renal cancer patients
      who achieved an objective response had a more profound thrombocytopenia during
      the first cycle of therapy. Patients with melanoma responded more frequently to
      interleukin-2 therapy when metastases were confined to subcutaneous tissue. In
      addition, responding patients with melanoma received more interleukin-2 in their
      first course and exhibited a more profound lymphocytosis 7 to 11 days after
      initiating therapy than did nonresponders. CONCLUSIONS: Renal cancer and melanoma
      displayed separate prognostic indicators with respect to response from
      interleukin-2 therapy. Although significant correlates to response were
      identified, there was much variability and a reliable predictive model of
      response to therapy could not be formulated based on these results.

PMID- 9166507
TI  - Long-term survival results for patients with locally advanced, initially
      unresectable non-small cell lung cancer treated with aggressive concurrent
      chemoradiation.
AB  - PURPOSE: Patients with locally advanced, initially unresectable non-small cell
      lung cancer (NSCLC) have a median survival time of 9 to 11 months, a 2-year
      survival rate of 13%, and a long-term survival rate of 5% to 7% when treated with
      radical thoracic radiation alone. Because of the preclinical radiosensitizing
      capabilities of 5-fluorouracil and cisplatin and the therapeutic synergy of
      etoposide and cisplatin, we combined these agents with full-dose radical thoracic
      radiation to determine the feasibility and efficacy of this approach in locally
      advanced NSCLC. METHODS: Patients with clinical stage IIIb and bulky IIIa NSCLC
      and ECOG performance status 0 or 1 received 5-fluorouracil infusion (640-800
      mg/m2/d CVI days 1-5, 29-34), cisplatin (20 mg/m2/d, days 1-5, 29-34), etoposide
      (50 mg/m2, days 1, 3, 5, 29, 31, 33) and concurrent thoracic radiation (60 Gy/2
      Gy/d/30 Fx). Patients with adequate cytoreduction proceeded to surgical
      resection. RESULTS: From March 1987 to July 1990, 41 patients were enrolled on
      study; 40 are evaluable. The objective response rate was 90%. Thirteen patients
      (39%), five with clinical stage IIIb disease and eight with IIIa disease,
      underwent thoracotomy and resection; three proved to have pathological complete
      remissions. Ten of 77 chemotherapy courses were complicated by neutropenic fever.
      Grade 3 or 4 esophagitis occurred in 21 patients (52%). Cardiac ischemia or
      infarction occurred in two patients (5%). There were seven deaths in the first 6
      months in the absence of disease progression. Two-year survival was 38%, 3-year
      survival 25%, and 4- to 5-year survival 18%. Six patients (15%) remain alive at
      the median follow-up time of 66 months (range, 64-84). CONCLUSIONS: Despite
      substantial early morbidity and mortality, concurrent, aggressive chemoradiation
      produced a long-term survival rate in locally advanced NSCLC comparable to other
      combined modality approaches. However toxicity, particularly esophagitis and
      postoperative complications, preclude the use of this regimen in phase III
      studies. Combined modality approaches for locally advanced, initially
      unresectable NSCLC have become standard; research must simultaneously focus on
      ways to enhance efficacy and reduce toxicity.

PMID- 9166508
TI  - The accumulation of multiple genetic abnormalities in individual tumor cells in
      human breast cancers: clinical prognostic implications.
AB  - PURPOSE: Human solid tumors undergo multiple genetic evolutionary changes as they
      evolve from the normal state to advanced stages of malignancy. This study
      characterizes the degree of advancement of primary human breast cancers in their
      genetic evolutionary pathways, and determines if this is of clinical
      significance. MATERIALS AND METHODS: Correlated cell-by-cell measurements of cell
      DNA content, HER-2/neu protein content per cell, and H-ras protein content per
      cell were obtained by means of multiparameter flow cytometry on primary tumors
      from 95 patients with clinically localized breast cancer. Laboratory findings
      were correlated with subsequent clinical course in 91 of these patients. RESULTS:
      Multiple genetic abnormalities were found to accumulate in individual cells in
      primary human breast cancers. Almost all tumors contained subsets of cells with
      one, two, or three abnormalities per cell in various combinations. After a median
      follow-up time of 32 months, 11 of 13 patients with early recurrence had primary
      tumors in which more than 5% of cells were hypertetraploid, overexpressed HER
      2/neu protein, and overexpressed H-ras protein (triple-positive cells). The
      duration of disease-free survival among patients with primary tumors that
      contained triple-positive cells was significantly shorter than for patients whose
      tumors did not contain triple-positive cells. The presence of subpopulations of
      cells with maximums of only one abnormality per cell or only two abnormalities
      per cell, in any combination, was of no prognostic significance. Among patients
      whose nodal status was known, 12 had recurrent disease, and all had positive
      axillary nodes. Among 36 patients known to have negative axillary nodes, no
      recurrence has been reported to date. CONCLUSIONS: The number of genetic
      abnormalities that accumulate in individual cells in primary breast cancers
      reflects the degree of advancement of a tumor in its genetic evolutionary
      sequence, and provides useful clinical prognostic information. Because follow-up
      duration is still relatively short, and because disease in node-negative patients
      tends to recur later than in node-positive patients, it is still too early to
      know if three measurements per cell will be sufficient to improve prognosis in
      node-negative disease.

PMID- 9166509
TI  - P53-independent apoptosis: a mechanism of radiation-induced cell death of
      glioblastoma cells.
AB  - PURPOSE: Radiation therapy, though routinely used in the treatment of patients
      with glioblastoma multiforme, is of limited efficacy in extending patients'
      lives. In this study we investigated the mechanism by which ionizing radiation
      causes death of glioblastoma cells in the hope of ultimately altering the
      intrinsic radioresistance of glioblastoma tumors. METHODS: Radiation survival in
      vitro was quantitated using linear quadratic and repair-saturation mathematical
      models. Radiation-induced apoptosis was assayed by fluorescence-activated cell
      sorter analysis, terminal deoxynucleotide transferase labeling technique, and
      chromatin morphology. Cellular distribution within the cell cycle was quantitated
      by dual labeling with propidium iodide and bromodeoxyuridine. RESULTS: We
      examined whether in vitro clonogenic radioresistance of glioblastoma would
      reflect their susceptibility to radiation-induced apoptosis and their ability to
      undergo a G1 arrest--two cellular functions associated with wild-type p53
      expression. We demonstrated that apoptosis contributed to the cytocidal effect of
      ionizing radiation on glioblastoma cells. The apoptosis observed in glioblastoma
      cell lines occurred in the absence of wild-type p53 expression. We identified a
      glioblastoma cell line expressing wild-type p53 and found that it did not exhibit
      radiation-induced apoptosis but rather underwent a prolonged G1 arrest not
      observed in any glioblastoma cell line lacking wild-type p53 expression.
      CONCLUSION: Apoptosis is an important component of the lethal effect of ionizing
      radiation on glioblastoma cells and does not require wild-type p53 expression.
      Glioblastoma expressing wild-type p53 exhibited no apoptosis, even after high
      radiation doses, but rather underwent a prolonged G1 arrest. The observation of
      p53-independent apoptosis and p53-dependent Gi arrest in glioblastoma cells have
      important radiobiologic and clinical implications.

PMID- 9166510
TI  - Neoadjuvant therapy.

PMID- 9166511
TI  - Complete debulking of epithelial ovarian cancer.

PMID- 9166512
TI  - The management of mammographically detected ductal carcinoma in situ: what is the
      best treatment?

PMID- 9166513
TI  - Primary central nervous system lymphoma: curable without toxicity?

PMID- 9166514
TI  - Should adjuvant tamoxifen therapy be stopped at 5 years?
AB  - Toxifen, a nonsteroidal antiestrogen, is currently the most widely used adjuvant
      therapy for the treatment of breast cancer. Though the efficacy of tamoxifen has
      been well documented in clinical trials, the certainty over the duration of
      therapy is less clear. Clinical and laboratory evidence suggests that longer
      therapy is better; however, whether this means 5 years, 10 years, or indefinite
      therapy has not been established in clinical trials. Essential to any study of
      long-term tamoxifen therapy is consideration of its effects not only on breast
      cancer but also on other estrogen target tissues. The estrogenic effect of
      tamoxifen that lowers serum lipids results in fewer hospital admissions for heart
      disease and a reduction in fatal myocardial infarction. Similarly, tamoxifen
      maintains bone mass that may ultimately result in fewer fractures. The effects of
      tamoxifen appear to parallel the effects of estrogen, so results from clinical
      trials of estrogen replacement therapy will provide a useful guide of what to
      expect with tamoxifen. The negative aspect of the therapy is a modest increase in
      the incidence of endometrial cancer. However, the incidence of endometrial cancer
      after stopping either estrogen or tamoxifen remains elevated for at least 5 years
      after the drug is stopped. Nevertheless, it is important to stress that the
      overall prognosis remains unaffected. We conclude that it will be difficult to
      demonstrate survival differences between 5 and 10 years of tamoxifen in clinical
      trials unless significant tamoxifen-stimulated recurrences occur with continued
      therapy. The benefits of tamoxifen must be calculated using estimates of the
      decreased rates of heart disease, contralateral cancers, decreased
      hospitalizations for fractures, and reduced cancer relapses.

PMID- 9166515
TI  - En bloc pelvic peritoneal resection of the intraperitoneal pelvic viscera in
      patients with advanced epithelial ovarian cancer.
AB  - PURPOSE: We report the results of 30 patients who underwent en bloc resection of
      the pelvic peritoneum and all intraperitoneal pelvic viscera in the management of
      advanced epithelial ovarian cancer. MATERIALS AND METHODS: Between 1989 and 1993,
      30 consecutive patients with advanced epithelial ovarian cancer underwent en bloc
      resection of the pelvic peritoneum and all pelvic viscera, except for the
      bladder, with a rectosigmoid reanastomosis below the peritoneal reflection. All
      30 patients were managed with gastrostomy and hyperalimentation. All patients
      received six cycles of platinum-based combination chemotherapy; the first cycle
      was administered prior to discharge. RESULTS: All patients underwent
      cytoreduction to the largest residual mass less than 1 cm. No major complications
      were attributed to the gastrointestinal surgery itself. The median hospital stay
      was 11 days (range, 7-23). We found 26 recurrences (87%) and 14 deaths (47%). The
      median times to recurrence and death were 12.5 months (range, 8-24) and 23 months
      (range, 8-63), respectively. Sixteen of the 26 relapses (62%) were found in
      extraperitoneal locations and 10 (38%) in intraperitoneal locations. Only 3 (12%)
      of the 26 relapses presented with bowel obstruction. CONCLUSIONS: En bloc
      resection of the uterus, ovaries, pelvic peritoneum, and rectosigmoid followed by
      low anterior anastomosis is a safe operation that facilitates complete
      cytoreductive surgery in poor prognosis patients with advanced epithelial ovarian
      cancer.

PMID- 9166516
TI  - Mammographically detected, clinically occult ductal carcinoma in situ treated
      with breast-conserving surgery and definitive breast irradiation.
AB  - PURPOSE: Ductal carcinoma in situ (DCIS) is increasingly detected as a
      nonpalpable lesion on mammographic screening performed for the early detection of
      breast cancer. Because of the growing incidence of mammographically detected
      DCIS, the present study was undertaken to determine the outcome of treatment of
      nonpalpable, mammographically detected intraductal carcinoma of the breast using
      breast-conserving surgery and definitive breast irradiation. MATERIALS AND
      METHODS: An analysis was performed of 110 women who presented with unilateral,
      nonpalpable, mammographically detected intraductal carcinoma of the breast and
      who were treated with breast-conserving surgery and definitive breast irradiation
      at 10 institutions in Europe and the United States. In all patients, complete
      gross excision of the primary tumor was performed, and breast irradiation was
      delivered with definitive intent. When performed, pathologic axillary lymph node
      staging was node negative (n=29). The median follow-up time was 9.3 years.
      RESULTS: The 10-year actuarial overall survival rate was 93%, and the 10-year
      actuarial cause-specific survival rate was 96%. The 10-year actuarial rate of
      freedom from distant metastases was 96%. There were 15 local recurrences in the
      treated breast. The actuarial rate of local failure was 7% at 5 years and 14% at
      10 years. The histology of the local recurrence was intraductal carcinoma in 9
      cases and invasive ductal carcinoma (with or without associated intraductal
      carcinoma) in 6 cases. The median time to local recurrence was 5.0 years (mean,
      5.4; range, 2.1-15.2). With a median follow-up time of 4.4 years after salvage
      treatment, 14 of the 15 patients with local recurrence were alive without
      evidence of disease at the time of last follow-up examination. The crude
      incidence of local recurrence was 7% (3/42) when the final pathology margin of
      tumor excision was negative, 29% (5/17) when the margin was close or positive,
      and 14% (7/51) when the margin was unknown. There was no difference in the rate
      of local recurrence based on pathologic characteristics of the primary tumor.
      DISCUSSION: Results from the present study demonstrate high rates of overall
      survival, cause-specific survival, and freedom from distant metastases at 10
      years following the treatment of nonpalpable, mammographically detected DCIS of
      the breast using breast-conserving surgery and definitive breast irradiation.
      Local recurrences within the treated breast were detected early and were treated
      with salvage for cure. These results support the initial treatment of
      nonpalpable, mammographically detected DCIS of the breast using breast-conserving
      surgery and definitive breast irradiation. Improvements in patient selection have
      the potential to reduce the risk of local recurrence.

PMID- 9166517
TI  - Non-AIDS primary CNS lymphoma: first example of a durable response in a primary
      brain tumor using enhanced chemotherapy delivery without cognitive loss and
      without radiotherapy.
AB  - PURPOSE: Radiographic tumor response and survival were evaluated in patients
      receiving methotrexate-based chemotherapy with osmotic blood-brain barrier
      disruption with or without antecedent cranial radiation. PATIENTS AND METHODS:
      Fifty-eight non-AIDS patients (38 males, 20 females) with histologically
      confirmed primary central nervous system lymphoma, primarily large cell or
      immunoblastic, were treated at the Oregon Health Sciences University from January
      1982 through March 1992. Group 1 patients (n=19) received cranial radiation prior
      to referral; Group 2 (n=39) received initial blood-brain barrier disruption
      chemotherapy. Ages ranged from 5 to 71 years (median, 57); Karnofsky performance
      status was 40% to 100% on inclusion (median, 80) and all underwent extensive
      baseline neuropsychological evaluation. RESULTS: There was no significant
      difference in patient characteristics between the two groups. In 15 evaluable
      Group I patients, 14 demonstrated objective response and 7 of 14 (50%) achieved
      complete response. In Group 2, 34 of 35 evaluable patients demonstrated objective
      response, including 29 of 34 with complete response. Estimated median survival
      times for Group 1 and Group 2 patients were 16 and 41 months, respectively.
      Currently, 19 Group 2 patients and 2 Group 1 patients are alive. Extensive
      neuropsychological follow-up (up to 7 years from baseline) was completed in 23
      patients, which demonstrated preservation or improved cognitive function in those
      receiving initial chemotherapy and blood-brain barrier disruption, most notably
      in patients older than 60 years. CONCLUSIONS: A plateau in survival curves
      suggests that a portion of primary central nervous system lymphoma patients may
      be cured with chemotherapy and blood-brain barrier disruption without the
      neurologic sequelae associated with cranial radiation.

PMID- 9166519
TI  - Methodology of the Practice Guidelines

PMID- 9166518
TI  - Targeting the epidermal growth factor receptor in breast cancer cell lines with a
      recombinant ligand fusion toxin (DAB389EGF).
AB  - PURPOSE: The epidermal growth factor receptor (EGF-R) is overexpressed frequently
      in breast cancer and other solid tumors. Targeting this receptor with an EGF
      ligand fusion toxin might selectively intoxicate cancer cells while minimizing
      toxicity to normal cells. DAB389EGF is a recombinant fusion toxin containing the
      enzymatically active and membrane translocation domains of diphtheria toxin and
      sequences for human EGF. After binding to EGF-R, the drug is internalized, the
      toxin is released, and inhibition of protein synthesis and cell death ensue. We
      examined the cytotoxic effects of DAB389EGF on a panel of breast cancer cell
      lines. MATERIALS AND METHODS: Protein synthesis, monolayer growth, and anchorage
      independent growth were studied in human breast cancer cell lines expressing low,
      intermediate, or high EGF-R concentrations. DAB389EGF concentrations and duration
      of exposure required for maximal effects were determined. Specificity of cellular
      cytotoxicity was assessed by reversing the effects with excess native EGF and by
      investigating the activity of two mutant analogs of DAB389EGF that either lack
      diphtheria toxin enzymatic activity or EGF-R binding activity. RESULTS: DAB389EGF
      inhibited protein synthesis in the cell line panel to a variable degree. Cell
      lines with low EGF-R levels were relatively resistant to the drug, while lines
      with intermediate to high receptor levels were very sensitive. Cell lines with
      intermediate or high EGF-R levels were exquisitely sensitive to DAB389EGF in
      monolayer and anchorage-independent growth assays with IC50 ranging from 3 to 50
      pM with a continuous drug exposure. Cell lines with low receptor levels were only
      moderately inhibited at a 1 nM drug concentration. Cytotoxicity was reversed by
      the addition of native EGF. Mutant analogs that were devoid of enzymatic or
      receptor binding activity were inactive. Cytotoxicity was dependent on both the
      drug concentration andduration of exposure; at a concentration of 1 nM, a 60
      minute exposure caused substantial cytotoxicity only for cells with very high EGF
      R concentrations. Longer treatment durations were required with cell lines
      expressing intermediate or low receptor concentrations. DISCUSSION: Breast cancer
      cell lines expressing intermediate to high levels of EGF-R are sensitive to low
      concentrations of DAB389EGF. This activity requires intact receptor binding and
      diphtheria toxin domains. DAB389EGF offers promise as a new therapeutic strategy
      for solid tumors such as breast cancer that overexpress EGF-R.

PMID- 9166520
TI  - Practice guidelines for breast cancer.

PMID- 9166522
TI  - Practice guidelines for esophageal cancer.

PMID- 9166521
TI  - Practice guidelines for colorectal cancer.

PMID- 9166523
TI  - Practice guidelines for gastric cancer.

PMID- 9166524
TI  - Practice guidelines for pancreatic cancer.

PMID- 9166525
TI  - Practice guidelines for non-small cell lung cancer.

PMID- 9166526
TI  - Practice guidelines for small cell lung cancer.

PMID- 9166527
TI  - Practice guidelines for prostate cancer.

PMID- 9166528
TI  - An approach to the radiosensitization of human tumors.
AB  - The use of biochemical modifiers of nucleotidc metabolism as clinical
      radiosensitizers holds renewed interest in the oncology community in light of the
      recently reported positive clinical trials cited in this article. In general,
      this approach to radiosensitization attempts to limit the effect of tumor
      repopulation and to reduce the efficiency of radiation damage repair in tumors
      during treatment. Since these drug-radiation interactions lack tumor specificity,
      further improvements in the therapeutic gain can only result by identifying
      exploitable differecnces in the biologic properties of tumors and dose-limiting
      normal tissues. The rapid evolution of our understanding of differences in cell
      cycle regulation in rumors and normal tissues is clearly one area that will
      likely provide new strategies for these combined modality approaches.

PMID- 9166529
TI  - Anal canal cancer--to split or not to split?

PMID- 9166530
TI  - The revolution in cancer molecular diagnostics.

PMID- 9166531
TI  - African-Americans and prostate cancer.

PMID- 9166532
TI  - Devices and desires: A simulations model of the early breast cancer overview.

PMID- 9166533
TI  - Dose escalation in chemoradiation for anal cancer: preliminary results of RTOG 92
      08.
AB  - PURPOSE: Radiation Therapy Oncology Group experience with chemoradiation for anal
      cancer has shown a local failure rate of 20% to 30% with radiotherapy doses of 45
      to 50 cGy. This study was undertaken to assess the effect of higher radiotherapy
      doses on toxicity, local control, and survival in this disease. MATERIALS AND
      METHODS: Forty-seven patients with anal cancers measuring > or = 2 cm were
      treated with a concurrent combination of two cycles of 5-fluorouracil infusion
      (1000 mg/m2 over 24 hrs for 4 days) and mitomycin C (10 mg/m2 bolus) plus 59.6 Gy
      of pelvic and perineal radiotherapy administered over 8.5 weeks, including a 2
      week rest period. Patients were followed for toxicity, disease status, and
      colostomy-free survival. Twenty-three (49%) patients had advanced (T3-4) primary
      tumors; 42 (92%) patients had NO disease, and 36 (77%) patients had squamous
      histology. For perspective, a comparative analysis was made with 147 patients
      treated on the previous RTOG protocol for anal cancers (RTOG 87-04) with
      identical chemotherapy but radiotherapy doses of 40 to 50.4 Gy. RESULTS:
      Transient hematologic and skin toxicity predominated during treatment or in early
      follow-up. One patient developed septicemia and died of multiple gastrointestinal
      toxicities. Twelve (26%) patients had greater than grade 3 complications and, of
      these, 9 (20%) had hematologic side effects alone. A comparative analysis with
      147 patients treated on RTOG protocol 87-04 showed no significant differences in
      pretreatment characteristics of disease extent, performance status, or histology.
      A mandatory 2-week split in the current chemoradiation protocol contrasted with
      12% of patients having a 2-week or greater treatment break in RTOG 87-04.
      Patients treated on the current protocol (RTOG 92-08) had a markedly lower
      incidence of > or = grade 3 dermal toxicity (34% vs. 55%) but a higher colostomy
      rate at 1 year (23% vs. 6%) and at 2 years (30% vs. 7%) compared with RTOG 87-04.
      CONCLUSIONS: Numerical increases in radiotherapy dose over those used in
      conventional chemotherapy regimens for anal cancers do not appear to increase
      local control when given in split-course fashion. For higher radiotherapy doses
      (> 50 Gy) to increase local control, radiation may have to be given in continuous
      fashion, which almost certainly means that our threshold of acceptable acute
      toxicity, particularly dermal toxicity, may have to be raised.

PMID- 9166534
TI  - Bcl-2 expression as a predictor of chemosensitivities and survival in small cell
      lung cancer.
AB  - PURPOSE: The bcl-2 gene belongs to a new category of oncogene that inhibits
      programmed cell death (apoptosis). No data are available on the frequency or
      clinical importance of its expression in patients with small cell lung cancer
      (SCLC), although its expression is reported in SCLC cell lines. We investigated
      the correlation between bcl-2 expression and prognosis, including response to
      chemotherapy, in SCLC patients and report our findings here. MATERIALS AND
      METHODS: Tumor specimens biopsied bronchoscopically in 38 SCLC patients were used
      for immunohistochemical study. Bcl-2 oncoprotein was detected by obtaining an
      immunostain using a specific monoclonal antibody, DAKO-bcl-2, 124. All patients
      received more than two courses of chemotherapy with 3- to 4-week intervals.
      RESULTS: We detected bcl-2 expression in 21 of the 38 SCLC patients (55%). In 17
      patients with bcl-2-negative tumors, the objective response to chemotherapy was
      76% with 12% complete response and in 21 patients with bcl-2-positive tumors it
      was 62% with 8% complete response. The difference in response rate was not
      significant. In patients with bcl-2-positive tumors, survival time tended to be
      shorter than in those with bcl-2-negative tumors. There was no significant
      correlation between bcl-2 expression and clinical factors (gender, age, smoking,
      performance score, staging). CONCLUSIONS: In 21 of the 38 SCLC patients bcl-2
      oncoprotein was abnormally expressed and its expression may be associated with
      shorter survival times and poor response to chemotherapy.

PMID- 9166535
TI  - P53 immunostaining predicts chemosensitivity in non-small cell lung cancer: A
      preliminary report.
AB  - PURPOSE: Although resistance to chemotherapy is a major problem in cancer
      treatment, there is no predictor of treatment response. Recent reports suggest
      that p53 status may provide a genetic basis for drug resistance. METHODS:
      Transbronchial biopsy specimens from 18 patients with non-small cell lung cancer
      were evaluated for p53 expression using anti-p53 antibody (DO-1). After biopsy,
      these patients received more than two courses of identical chemotherapy including
      cisplatin, carboplatin, and vindesine. RESULTS: Ten of 18 (56%) patients
      responded to chemotherapy. The accumulation of p53 protein was detected in 10 of
      18 (56%) patients. Positive staining for p53 was significantly correlated with
      unresponsiveness to chemotherapy. Other factors, including gender, performance
      status, body weight loss, serum albumin, and serum LDH, did not correlate with
      the immunohistochemical expression of p53. CONCLUSIONS: These results suggest
      that immunostaining with p53 can be a predictor of the response to chemotherapy
      in non-small cell lung cancer. Further studies are needed to confirm the
      relationship between p53 expression and chemosensitivity.

PMID- 9166536
TI  - Growth suppression of esophageal cancer cells by p16INK4 and p15INK4B in vitro.
AB  - PURPOSE: We investigate whether p16INK4 and p15INK4B inhibit cellular
      proliferation and exert a growth suppressive effect on esophageal cancer cells.
      MATERIALS AND METHODS: The growth suppressive effects of p16INK4 and p15INK4B
      were evaluated by transfecting vectors containing the p16INK4 cDNA or the
      p15INK4B cDNA, or both, constitutively driven by a cytomegalovirus promoter, into
      two human esophageal cancer cell lines containing or lacking endogenous p16INK4
      and/or p15INK4B. RESULTS: These experiments demonstrated that in both cells lines
      tested, the numbers of cells surviving dramatically decreased in p16INK4
      transfected and p15INK4B-transfected cells compared with control vector
      transfected cells. There was no significant difference in the degree of growth
      inhibition between p16INK4-transfected and pI5INK4B-transfected cell lines.
      CONCLUSIONS: These results suggest that p16INK4 and p15INK4B play important roles
      in the initiation or promotion of esophageal cancer. The inactivation of p16INK4
      and p15INK4B may contribute to uncontrolled growth in human cancer.

PMID- 9166537
TI  - Prostate-specific antigen levels in African-Americans correlate with insurance
      status as an indicator of socioeconomic status.
AB  - PURPOSE: African-Americans have a higher age-adjusted incidence and a higher
      disease-specific mortality than whites. Two potential causes are differences in
      biology or socioeconomic status, the latter leading to differences in access,
      delivery, or utilization of health care. In this study, we compare serum prostate
      specific antigen (PSA) levels for comparable stage and grade-disease, as well as
      individual insurance status. PSA is a demonstrated indicator of the size and
      virulence of tumor and is correlated with prognosis. Insurance status has been
      linked with income and education and is an indicator of access to medical care.
      PATIENTS AND METHODS: All patients were referred to the University of Chicago
      Center for Radiation Therapy (UCCRT) with stages A-C (T1-4) prostate cancer. They
      were seen in four different facilities, designated A through D, and were
      evaluated and staged by the faculty of UCCRT using the same criteria. Hospitals A
      and B are large teaching hospitals located within the city of Chicago; C and D
      are suburban and urban community hospitals, respectively. A total of 341 patients
      seen between May 1987 to November 1992 are included in this study. RESULTS: In
      univariate analysis, PSA levels were significantly associated with stage, grade,
      and race. Higher mean PSA levels were seen with increasing clinical stage and
      grade. African-Americans had higher mean values than whites. Private insurance
      and managed care patients had lower values than Medicare-only patients. Within
      each race, the above results were reproduced, except for insurance status, which
      was significant only in African-Americans. In multivariate analysis, stage,
      grade, and insurance status were significant in African-Americans, whereas only
      stage and grade were significant in whites. Within comparable insurance status,
      stage, and grade, no racial differences were found, except among Medicare-only
      patients, with African-Americans who had stage B or grade 2 disease having higher
      mean PSA levels than whites. Racial differences were seen at hospital B, but not
      at hospital A. No racial comparisons could be made at hospitals C or D due to an
      insufficient number of African-American patients. At hospital A, whites and
      African-Americans had comparable private plus HMO insurance distributions (81.1%
      and 86.9%, respectively); at hospital B, the distribution was quite different-
      only 4.4% of whites had Medicare-only insurance while 31.8% African-Americans had
      no supplementary insurance. For all patients in the multivariate analysis, racial
      difference was seen only among Medicare-only patients. CONCLUSIONS: Our results
      suggest that socioeconomic differences are responsible for the racial differences
      noted in prostate cancer. Our findings of higher PSA levels in African-American
      Medicare-only patients may result from the many African-Americans
      disproportionately uninsured throughout their lives compared with whites and thus
      using services at later stages of disease. A second possible explanation is
      cultural or ethnic differences in care-seeking behavior, with poorer African
      Americans less likely to pursue care for disease until it has progressed. Our
      findings can explain the dichotomy of poorer overall outcome among African
      Americans with prostate cancer, but comparable stage-adjusted outcome with
      comparable treatments between African-Americans and whites.

PMID- 9166538
TI  - Simulations model for predicting survival in women receiving adjuvant therapy for
      early breast cancer.
AB  - PURPOSE: In 1990, a worldwide overview of the randomized trials of all aspects of
      the systemic treatment of early breast cancer was undertaken by the Early Breast
      Cancer Trialists' Collaborative Group. We used the overview data to develop a
      simulations model to assess and compare the potential benefits of various
      adjuvant therapies. METHODS: The model consists of an expert system, a
      simulations module, a graphical user interface, and an output module. RESULTS:
      The model has shown that tamoxifen benefited all women regardless of age or
      estrogen-receptor status. However, absolute gains in disease-free survival and
      life expectancy compared with controls were higher in women younger than 50 years
      of age. Prolonged chemotherapy showed absolute benefits in disease-free survival
      and life expectancy for all age groups and all nodal states, but the magnitude of
      absolute benefit appeared smaller in older women. The magnitude of the absolute
      gain in disease-free survival and life expectancy achieved by ovarian ablation in
      patients younger than 50 years of age was equal to or better than that attained
      by tamoxifen or prolonged chemotherapy. Ovarian ablation added to chemotherapy in
      young patients has demonstrated an improvement in disease-free survival and life
      expectancy superior to that achieved by chemotherapy alone. On the other hand,
      particularly for women younger than 50 years, the magnitude of the survival gain
      accomplished by combining tamoxifen and chemotherapy versus each modality alone
      was greater for disease-free survival than for life expectancy. CONCLUSIONS: We
      illustrate the development process and outcome of a robust tool for reasoning and
      decision-making. The limitations of the model are discussed.

PMID- 9166539
TI  - Genetic predisposition testing for breast cancer.

PMID- 9166540
TI  - "First do no harm" also applies to cancer susceptibility testing.

PMID- 9166541
TI  - The importance of locoregional control of cervical cancer--why is it still
      controversial?

PMID- 9166542
TI  - Patterns of spread in node-positive cervical cancer: the relationship between
      local control and distant metastases.
AB  - PURPOSE: The presence of metastatic pelvic nodes in stage I and II cervical
      cancer predicts for pelvic and distant recurrence. Whether this malignancy is a
      systemic disease at onset or locoregionally advanced disease is unclear. To
      examine this issue, we reviewed cases of node-positive stage I and II cervical
      cancer to analyze the patterns of spread and the relationship between local
      control and distant metastasis. MATERIALS AND METHODS: Between 1964 and 1993, 163
      patients with FIGO stage I-II cervical cancer underwent exploratory laparotomy
      and bilateral pelvic lymph node dissection and were found to have metastatic
      pelvic nodes. Patients with positive para-aortic nodes were excluded. Of these
      patients, 108 underwent radical hysterectomy and postoperative pelvic
      irradiation, 35 underwent radical hysterectomy without postoperative pelvic
      irradiation, and 20 did not undergo radical hysterectomy and were treated with
      definitive radiation therapy. RESULTS: The overall 5- and 10-year actuarial
      disease-free survival rates for the entire group were 55% and 49%, respectively.
      The 5- and 10-year actuarial pelvic failure rates were 30.5% and 37%,
      respectively. The actuarial distant metastatic rates at 5 and 10 years were 30%
      and 34%, respectively. Patients who were controlled in the pelvis (114) had
      significantly lower rates of developing distant metastases at 5 and 10 years (21%
      and 22%, respectively) compared with patients who failed in the pelvis (49) with
      rates of 59% and 84%, respectively. Multivariate analysis found that pelvic
      failure had the strongest association with the development of distant metastases.
      Using the formula of Suit et al to assess potential improvement in cure from
      perfect local and distant control, survival advantages from increased local and
      distant control were 24% and 21%, respectively. Of those patients who failed both
      locally and distantly (22), 27% failed distantly 6 months or more after failing
      locally. CONCLUSIONS: Early-stage node-positive cervical cancer is associated
      with both increased distant and local failure. There appear to be two patterns of
      disease spread: patients whose disease is locoregional, in whom improvements in
      local control can result in improved cure, and patients with biologically
      aggressive cancer, who probably have disseminated disease at presentation, in
      whom improved locoregional control will not be enough to increase survival but
      who require improved distant control.

PMID- 9166543
TI  - Tumor-infiltrating lymphocytes from human ovarian cancer patients recognize
      autologous tumor in an MHC class II-restricted fashion.
AB  - PURPOSE: To search for tumor-specific in vitro reactivity by lymphocytes derived
      from patients with ovarian carcinoma. METHODS: Tumor-infiltrating lymphocytes
      (TIL) were derived from primary or metastatic solid tumors and tumor-associated
      lymphocytes (TAL) were derived from ascites from 13 patients with ovarian cancer.
      TIL or TAL were cultured for approximately 30 to 60 days and studied for
      phenotype, cytotoxicity, and cytokine secretion in response to autologous tumor
      stimulation. RESULTS: Twenty-nine bulk TIL or TAL cultures were successfully
      established from 10 patients using various culture conditions. Thirteen cultures
      were predominantly CD4+ and 16 were mainly CD8+. In contrast to reports by
      others, none of the cultures tested were specifically lyric for autologous tumor.
      Five predominantly CD4+ bulk TIL (from four patients) preferentially secreted
      tumor necrosis factor-alpha and granulocyte macrophage-colony stimulating factor
      when stimulated with autologous tumor and not when stimulated by autologous
      Epstein Barr virus-B cells, fibroblasts, peripheral blood mononuclear cells, or
      allogeneic HLA matched or mismatched stimulators. This cytokine secretion was
      found to be MHC class-II restricted in three patients because it was inhibited by
      the anti-MHC class-II antibody IVA12 and the HLA-DR specific antibody L243.
      CONCLUSION: We believe these data are the first to suggest that tumor reactive
      CD4+ lymphocytes exist in some ovarian cancer patients. This finding may be
      useful in the development of novel immunotherapies for these patients.

PMID- 9166544
TI  - Protection from radiation-induced alopecia with topical application of
      nitroxides: fractionated studies.
AB  - PURPOSE: Hair loss resulting from irradiation of the head and neck or from whole
      brain irradiation often leads to cosmetic, social, and psychological problems for
      the radiotherapy patient. Few successful clinical interventions are available. We
      have shown that nitroxides (stable free radicals) afford radiation protection
      against single-dose radiation-induced alopecia in a guinea pig model. Here we
      determine if topical nitroxide application provides protection from fractionated
      radiation treatment. MATERIALS AND METHODS: Two symmetrical and contralateral
      areas (3 x 5 cm) of skin on the dorsal trunk of guinea pigs were shaved to a hair
      length of 0.25 cm. A 2 mL solution containing 70 mg/mL nitroxide (Tempo or
      Tempol) in 70% ethanol was topically applied to the skin surface of one side; 70%
      ethanol was applied to the contralateral (control) side 10 minutes before
      irradiation. Animals were placed in a special jig that held skin without
      decreasing blood flow to the treatment area and fractionated external beam
      radiation (7 Gy) was delivered daily for eight fractions over 10 days via a 4 MeV
      linear accelerator. Alopecia (hair density) was scored weekly for 13 to 14 weeks
      after radiotherapy, using a standardized reference with respect to hair loss and
      regrowth in the treatment field. RESULTS: After radiation treatment, dry
      desquamation and gradual hair loss were observed for both control and nitroxide
      treated skin; however, over weeks 4 to 11 postirradiation hair loss was much more
      pronounced in control animals when compared with nitroxide-treated animals. Hair
      density measurements for Tempol treatment over weeks 9 to 13 were approximately
      75% compared with measurements in controls of approximately 25%. Tempo-treated
      animals exhibited hair density values of approximately 90% compared with 12% in
      controls over weeks 11 to 14. Tempol and Tempo treatments resulted in significant
      radioprotection. Histologic evaluation showed that radiation treatment alone in
      ethanol controls resulted in a marked decrease in the number of hair follicles
      and poor development of remaining follicles; however, nitroxide pretreatment
      resulted in no appreciable decrease in hair follicles and hair follicles appeared
      mature. This was also observed in unirradiated ethanol controls. Electron
      paramagnetic resonance studies revealed that topical nitroxide application did
      not result in measurable systemic concentrations of either drug. CONCLUSIONS: The
      results of this study suggest that topical application of nitroxides may be
      useful in a clinical setting to reduce the undesirable toxicity of radiation
      induced alopecia.

PMID- 9166545
TI  - Angiogenin, interleukins, and growth-factor levels in serum of patients with
      ovarian cancer: correlation with angiogenesis.
AB  - PURPOSE: Because tumor angiogenesis is critical to the development of ovarian
      tumors, we devised an experiment to study changes in the serum levels of
      angiogenin, growth factors, and interleukins, which can act as modulators of
      angiogenesis, in patients with ovarian cancer during various clinical stages.
      PATIENTS AND METHODS: Serum levels of angiogenin, growth factors, and
      interleukins were assayed by the enzyme-linked immunosorbent assay in 56 women
      with ovarian cancer (stages I through IV) and were compared to levels of the same
      in 12 control subjects. RESULTS AND DISCUSSION: Women with stage I tumors had
      significantly increased serum levels of beta-fibroblast growth factor,
      interleukin-8, and interleukin-10. The serum levels of tumor necrosis factor-beta
      and interleukin-7 were significantly elevated only in stage II disease.
      Angiogenin and transforming growth factor-beta serum levels were significantly
      elevated only in stages II and III. Interleukin-2, interleukin-6, tumor necrosis
      factor-alpha, and granulocyte macrophage-colony stimulating factor serum levels
      were elevated consistently in stages III through IV; however, serum levels of
      interleukin-1 alpha and interleukin-1 beta were not altered in any stage of tumor
      progression in comparison with controls. Progression of ovarian cancer through
      clinical stages is associated with increased serum levels of angiogenin,
      cytokines, and growth factors, which possibly act as angiogenic amplifiers.

PMID- 9166546
TI  - Phase I study of paclitaxel with oral etoposide in advanced solid tumors.
AB  - PURPOSE: This study evaluated dose escalation of paclitaxel administered as a 3
      hour infusion after a fixed oral etoposide regimen given daily for 10 days to
      determine an optimal dose and a toxicity profile for this combination. PATIENTS
      AND METHODS: Three consecutive cohorts consisting of 29 patients with measurable
      or assessable advanced solid tumors were treated with paclitaxel by intravenous
      infusion over 3 hours after receiving etoposide, 50 mg orally twice daily, for 10
      days. Cycles were repeated every 28 days. Paclitaxel dose levels were: cohort 1,
      135 mg/m2; cohort 2, 150 mg/m2; and cohort 3, 175 mg/m2. RESULTS: Dose-limiting
      toxicity was observed in cohort 3 in 5 of 12 patients (4 of 12 patients met
      criteria for myelosuppression and 1 of 12 experienced grade 3 mucositis). No
      unexpected toxicities were observed, and this regimen was well tolerated.
      DISCUSSION: Administration of paclitaxel in combination with a prolonged oral
      schedule of etoposide is feasible and toxicities are manageable. The dose
      limiting toxicity of a 3-hour infusion of paclitaxel after 10 days of etoposide
      given orally was myelosuppression. Recommended doses of this combination for
      phase II studies are etoposide, 100 mg orally daily for 10 days, followed by
      paclitaxel at a dose of 150 mg/m2 intravenously over 3 hours, and repeated every
      4 weeks.

PMID- 9166547
TI  - Growth and metastasis of surgical specimens of human breast carcinomas in SCID
      mice.
AB  - PURPOSE: We have studied the growth and metastatic potential of surgical
      specimens of breast carcinomas engrafted into the large abdominal (gonadal) fat
      pad of severe combined immunodeficient (SCID) mice. We present results of this
      study, details of the implantation protocol and histologic characterization of
      several of the tumor xenografts. MATERIALS AND METHODS: We evaluated the growth
      within SCID mice of 48 breast carcinoma specimens derived from 46 patients (45
      primary breast cancers or local recurrences and 3 regional metastatic lymph
      nodes) obtained from resected tissues at this Institute over a 3-year period. The
      growth of each transplant was assessed by histologic examination of the
      xenografts at various times after implantation or upon passage into additional
      mice. RESULTS: We observed that placement of human breast tumors within the
      gonadal fat pad could result in tumors that grew either rapidly, slowly, or not
      at all. Of 48 tumors studied, 12 (25%), including one of the three lymph node
      derived tumors, grew rapidly enough within some or all of the implanted mice
      (i.e., the tumors reached a diameter of 2-3 cm within 2-6 months) to allow
      repeated passage. Metastatic spread to the SCID mouse lung, liver, and/or
      diaphragm and other sites was observed with the xenografts derived from 8 of
      these 12 rapidly growing tumors. Tumors in a second category often took from 6
      months to over 1 year to only double or triple in size. This slow-growth group
      consisted of 25 patients' tumors (53%), including the remaining two metastatic
      lymph node-derived tumors. These xenografts would usually maintain a slow growth
      rate even upon later passage into new animals. A third category consisted
      ofpatients' tumors (23%) that failed to grow at all (i.e., no evidence of tumor
      growth in any of the mice implanted), as discerned by histologic evaluation at
      various times after implantation. Histologic examination of tumor xenografts and
      metastatic tumors revealed considerable variation in histopathology among the
      different patients' tumors. DISCUSSION: Further examination of the heterogeneous
      properties of primary human breast carcinomas within SCID mice may provide a
      simple yet valuable new approach for the long-term study of human breast cancer
      biology. Importantly, use of the protocol described here can often permit the
      isolation of substantial quantities of human breast cancer cells for biochemical
      and molecular analyses. The ability to passage patients' breast tumors into large
      numbers of mice will permit the preclinical testing of new therapies for the
      treatment and prevention of this disease.

PMID- 9166548
TI  - Progress in unresectable stage III non-small cell lung cancer.

PMID- 9166549
TI  - Charrrrrge!

PMID- 9166550
TI  - Improving the results of bone marrow transplants.

PMID- 9166551
TI  - Accelerated-interrupted radiation therapy given concurrently with chemotherapy
      for locally advanced non-small cell lung cancer.
AB  - PURPOSE: To evaluate the efficacy of multidrug chemotherapy combined with
      accelerated radiation therapy in the treatment of localized but unresectable non
      small cell lung cancer. PATIENTS AND METHODS: Between September 1990 and February
      1993, 35 patients with Stage III (15 IIIA & 20 IIIB) non-small cell lung cancer
      were entered on a protocol using combined accelerated radiation therapy and
      chemotherapy. Radiation therapy consisted of 55.6 Gy in 30 fractions (1.8 Gy bid
      for 5 consecutive days given in 3 weeks [total of 15 days], every other week).
      Chemotherapy consisted of cisplatin (10 mg/m2), vinblastine (4 mg/m2), 6
      thioguanine (40 mg bid), and 5-fluorouracil (400 mg/m2 as continuous infusion)
      given concomitantly with radiation therapy. Approximately 3 weeks following
      completion of radiation therapy, two cycles of consolidation chemotherapy were
      given, consisting of two doses of cisplatin (120 mg/m2) 4 weeks apart and six
      doses of vinblastine (4 mg/m2) given on two consecutive days every other week for
      3 weeks. RESULTS: Six patients were still alive at last follow-up; for them the
      median follow-up time is 47 months (range, 39-55.8). The median survival time is
      17.5 months. The 1-, 2-, 3- and 4.5-year survival rates are 69%, 37%, 20% and
      17%, respectively. Overall response rate is 63%, with 51.5% partial response and
      11.5% complete response rates. Esophagitis occurred as follows: Grade 4 = 0,
      Grade 3 = 1, Grade 2 = 6, and Grade 1 = 13. No patient developed Grade 3 or 4
      acute respiratory toxicity. Significant hematologic toxicity occurred as follows:
      37% Grade 3 and 31% Grade 4 leukopenia. Radiation pneumonitis occurred in two
      patients. DISCUSSION: The regimen tested in this protocol appears to be very well
      tolerated with minimal pulmonary or esophageal toxicity. This, coupled with the
      shortened course of radiation therapy and the ability to deliver the combined
      radiation and chemotherapy portion of the treatment on an outpatient basis most
      of the time, has made multi-modality treatment for this malignancy much easier
      and more convenient for patients. In addition, the favorable survival in this
      group of patients with locally advanced disease is very encouraging and warrants
      further study.

PMID- 9166552
TI  - Local control after the use of adjuvant electron beam intraoperative radiotherapy
      in patients with high-risk head and neck cancer: the UCSF experience.
AB  - PURPOSE: We assess the effect of electron beam intraoperative radiotherapy (EB
      IORT) on local-regional control and any associated complications in patients with
      locally advanced or recurrent head and neck cancer. MATERIALS AND METHODS: The
      records of 30 patients with head and neck cancer who received EB-IORT from March
      1991 to December 1994 were retrospectively reviewed. The indications for EB-IORT
      in 25 patients were recurrent or persistent disease despite previous treatment
      with full-course external-beam radiotherapy and/or one or more resections. In
      five other cases the indication was extensive primary disease with multiple high
      risk factors for local recurrence, including extension into the base of the
      skull, advanced extensive disease, and perineural or bony invasion. All patients
      had a Karnofsky performance score > or = 70 prior to EB-IORT. Median age was 65
      years. Final pathology revealed positive or close surgical margins in all
      patients. The areas treated were generally inaccessible to catheter placement for
      brachytherapy. The most common histology was squamous cell carcinoma. EB-IORT was
      given as a single fraction of 1500 cGy to the 90% isodose with 6 or 9 Mev
      electrons using cone sizes ranging from 2.5 to 7 cm in diameter. Data were
      analyzed to determine the local-regional control rate, survival, and
      complications after EB-IORT. RESULTS: With a median follow-up time of 30 months,
      nine patients (27%) had only local recurrence. Of these, only one recurrence was
      inside the EB-IORT field and eight were outside the EB-IORT field. Two patients
      (7%) developed distant metastases only and one patient (3%) had both local
      recurrence and distant metastasis. Seven patients died, five with disease. Twenty
      two patients are known to be alive, 15 (68%) of whom have no evidence of disease.
      One patient was lost to follow-up after 12 months; when last examined he was free
      of disease. Five patients (16%) have had mild-to-moderate transient complications
      probably related to EB-IORT. The 3-year actuarial local-regional control rate was
      60%. CONCLUSIONS: Our data suggest that EB-IORT may play an important role in
      decreasing local recurrence in patients with multiple high-risk factors. Despite
      previous full-course external beam radiotherapy and extensive resections, EB-IORT
      did not confer significant additional long-term morbidity. Although results are
      encouraging, randomized studies are required to definitively establish the role
      of EB-IORT in the management of advanced or recurrent head and neck cancer.

PMID- 9166553
TI  - Allogeneic matched T-cell-depleted bone marrow transplantation for acute leukemia
      patients.
AB  - PURPOSE: We evaluated the efficacy and toxicity of a conditioning regimen
      designed to overcome the increased risk of rejection and relapse associated with
      T-cell-depleted bone marrow transplants. PATIENTS AND METHODS: Fifty-four
      patients with acute leukemia received an allogeneic T-depleted bone marrow
      transplant from an HLA-matched (n=52) or one locus mismatched (n=2) sibling donor
      between June 1989 and November 1993. Nineteen acute myeloid leukemia patients and
      17 acute lymphoid leukemia patients were in complete remission, and 11 acute
      myeloid leukemia patients and 7 acute lymphoid leukemia patients were in relapse.
      Patients were preconditioned with hyperfractionated total body irradiation of 1.2
      Gy three times a day on days -9 to -6 (total 14.4 Gy), 10 mg/kg thiotepa on day 
      5, 4 mg/kg rabbit antithymocyte globulin on days -4 to -1, and 50 mg/kg
      cyclophosphamide on days -3 and -2. RESULTS: All patients were fully engrafted at
      a median of 15 days after transplant. No patient rejected the transplant or
      developed acute or chronic graft-versus-host disease. Of 19 patients with acute
      myeloid leukemia in complete remission, 14 survive. Four of the 11 patients with
      acute myeloid leukemia in relapse survive. Twelve acute myeloid leukemia patients
      died (three of relapse, eight of toxicity, one of other causes). Eleven of 24
      patients with acute lymphoid leukemia (one treated in relapse) are alive in
      complete remission; the other 13 died (nine of relapse, four of toxicity).
      Interstitial pneumonia, the main cause of toxic death, occurred in 9.26% of total
      patients. The median follow-up time at this writing is 30 months. CONCLUSIONS:
      The absence of rejection and graft-versus-host disease and the relatively low
      relapse and toxicity rates are evidence for the efficacy of our conditioning
      regimen.

PMID- 9166554
TI  - Factors influencing survival after gamma knife radiosurgery for patients with
      single and multiple brain metastases.
AB  - PURPOSE: Radiosurgery has been reported to yield high local control rates for
      brain metastases. However, further work is needed to define which subgroups of
      patients may benefit from this treatment modality. PATIENTS AND METHODS: We
      reviewed 116 patients who underwent stereotactic radiosurgery for initial
      management or recurrence of solitary or multiple brain metastases from September
      1991 through December 1994 at the University of California, San Francisco.
      Survival time and time to local-regional failure were calculated using the Kaplan
      Meier method. Univariate and multivariate analyses were performed using the Cox
      proportional hazards model. RESULTS: Median survival was 40 weeks from
      radiosurgery. In multivariate analysis, smaller total tumor volume, absence of
      extracranial metastases, higher Karnofsky score, and age < or = 70 had a positive
      effect on survival. In patients initially managed for brain metastases, the
      addition of whole brain radiotherapy to radiosurgery had no significant effect on
      survival. Although the presence of multiple metastases was associated with a
      significantly worse survival rate in patients initially managed with radiosurgery
      in univariate analysis, it was not as a significant factor in multivariate
      analysis. An analysis of patients within this series treated with radiosurgery
      who would have been eligible for Patchell's study on the role of surgery in the
      treatment of solitary brain metastasis revealed a favorable median survival of 70
      weeks. CONCLUSIONS: We conclude that radiosurgical treatment of brain metastases
      results in survival times that compare favorably with the historic experience in
      patients treated with whole brain radiotherapy alone or with surgical resection.
      In patients presenting initially with brain metastases, radiosurgery alone may
      yield survival results equivalent to radiosurgery with whole brain radiotherapy,
      but intracranial control and quality of life also need to be evaluated. Also, the
      presence of multiple brain metastases should not be a contraindication for the
      use of radiosurgery given the good survival achieved with such patients in this
      series. Each such case should therefore be evaluated based on other factors such
      as patient's age, Karnofsky score and systemic disease.

PMID- 9166555
TI  - Role of percent positive biopsies and endorectal coil MRI in predicting prognosis
      in intermediate-risk prostate cancer patients.
AB  - PURPOSE: This study was performed to determine the clinical factors that can
      optimize preoperative staging for clinically localized intermediate-risk prostate
      cancer patients. MATERIALS AND METHODS: Logistic and Cox regression multivariable
      analyses were performed on 480 prostate cancer patients whose disease was
      confined to the prostate to evaluate the ability of clinical stage, prostate
      specific antigen (PSA), biopsy Gleason sum, percent positive biopsies, and
      endorectal coil magnetic resonance imaging (MRI) results to predict pathologic
      established extracapsular extension, seminal vesicle invasion, and time to
      postoperative PSA failure in patients with clinically localized prostate cancer.
      Intermediate risk was defined as PSA 4-10 ng/mL and Gleason sum 5-7; PSA 10-20
      ng/mL and Gleason sum < or = 7. RESULTS: Intermediate-risk patients with at least
      50%, 67%, 83%, or 100% positive biopsies have disease pathologically confined to
      the prostate at least 45% of the time; however, if an endorectal coil MRI is
      positive for either capsular penetration or seminal vesicle invasion, no more
      than 29% of patients have pathologically determined organ-confined disease. No
      intermediate-risk patient with both a positive MRI and at least 50% positive
      biopsies had pathologically determined organ-confined disease. Intermediate-risk
      patients with less than 50% positive biopsies had pathologically determined organ
      confined disease in at least 77% of the cases. CONCLUSIONS: Intermediate-risk
      patients with an endorectal coil MRI showing extracapsular extension or seminal
      vesticle invasion are at high risk for early postoperative PSA failure. The
      concomitant presence of at least 50% positive biopsies increases this risk to
      unity. Therefore, these patients are not good candidates for surgery alone
      because of their high risk of extraprostatic disease and should be considered for
      entry onto phase III trials examining the effect of adding androgen-deprivation
      therapy to definitive local therapy (external-beam radiation therapy or surgery)
      on overall survival. The subgroup of intermediate-risk patients likely to benefit
      from an endorectal coil MRI are those patients with PSA > 10-20 ng/mL; biopsy
      Gleason score < or = 7, and at least 50% positive biopsies representing
      approximately 7.5% of the total patient population.

PMID- 9166557
TI  - Lessons learned about treatment of the more common neoplasms from the study of
      acute leukemia.

PMID- 9166556
TI  - Tumorigenicity, oncogene transfection, and radiosensitivity.
AB  - PURPOSE: Reports that the incorporation of exogenous oncogenes confer
      radioresistance have excited interest and controversy. We investigate whether
      human cell lines transformed to a malignant phenotype by gamma-rays or by
      chemicals became radioresistant. MATERIALS AND METHODS: Rodent intestinal
      epithelial cells immortalized by the HPV virus, human immortalized
      bronchoepithelial cells and their malignant counterparts transformed by alpha
      particles, uroepithelial cells and their malignant counterparts transformed
      either by alpha-particles or methylcholanthrine-4, and osteosarcoma cells and
      their nonmalignant counterparts into which the Rb gene had been introduced were
      used. Dose response curves for all of these cell lines were obtained by exposure
      to cesium 137 gamma-rays at a dose-rate of 1.18 Gy/min. RESULTS: There was a
      dramatic increase in resistance to gamma-rays when H-ras was transfected into
      rodent intestinal epithelial cells. By contrast, in the case of the three human
      cell lines used, no consistent or significant change of radiosensitivity occurred
      when normal cells were transformed to a malignant state by alpha-particles or by
      a chemical carcinogen. CONCLUSIONS: Experiments involving the introduction of
      foreign oncogenes to cause tumorigenicity and accompanying radioresistance do not
      have direct relevance in human tumors. In a number of different instances, the
      conversion to malignancy by means that more closely reflect what happens in
      practice (i.e., by radiation or a chemical carcinogen) is not necessarily
      accompanied by an increased radioresistance to low doses of radiation.

PMID- 9166559
TI  - High-resolution MRI of pancreatic masses with a new circularly polarized body
      phased-array coil.
AB  - A total of 18 patients with clinical suspicion of a pancreatic tumor underwent
      dynamic contrast-enhanced CT and MRI examinations. A fat-suppressed T1-weighted
      2D fast-low-angle-shot (FLASH) sequence and a T2-weighted spin-echo (SE) sequence
      were applied in a transverse orientation using a circularly polarized (CP) body
      phased-array coil. The FLASH sequence was repeated after Gd-DTPA administration.
      The highest spatial resolution was 1.37 x 1.37 x 3.00 mm3. In two cases a half
      Fourier single-shot turbo-SE sequence (HASTE) was additionally applied. In a
      comparison between CT and MRI, pancreatic masses could be demonstrated and
      characterized with excellent image quality. The fat-saturated 2D FLASH sequence
      yielded the highest contrast-to-noise ratios after Gd-DTPA administration between
      pancreas and inflammatory or neoplastic lesion. One non-contour deforming
      carcinoma could be detected only with MRI and was only retrospectively visible on
      CT with an element of uncertainty. Magnetic resonance imaging using a CP body
      phased-array coil and fat-suppressed T1- and T2-weighted FLASH, SE, and turbo-SE
      sequences offers diagnostic possibilities in improved imaging of the pancreas.

PMID- 9166558
TI  - Imaging of primary small intestinal tumours by enteroclysis and CT with
      pathological correlation.
AB  - Preoperative diagnosis of primary small intestinal neoplasms can be a challenge
      for both clinicians and radiologists. As a result of their infrequent occurrence,
      they invariably present difficult problems in diagnosis and management. These
      problems are reflected mainly in the delayed treatment and a very poor prognosis
      for such malignant tumours. Their morphological changes, however, shown in
      enteroclysis and CT, correlate almost perfectly with the lesions identified in
      the gross pathological specimens. This ability to accurately image a small
      intestinal neoplasm, independently of its size, anatomical localization and
      growing tendency, represents a major improvement in the diagnosis and management
      of these neoplasms. This paper, based on a large series of patients with primary
      small intestinal neoplasms, focuses on the recognition of their detailed
      radiological appearances when evaluated by enteroclysis and CT.

PMID- 9166560
TI  - Magnetic resonance angiography in the resectability assessment of suspected
      pancreatic tumours.
AB  - The aim of this prospective study was to evaluate MRI, including MR angiography
      (MRA), in the preoperative assessment of the resectability of suspected
      malignancy of the pancreas. A total of 17 patients with suspected pancreatic
      carcinoma and planned surgery were investigated with conventional angiography,
      ultrasonography with Doppler technique, MRI and MRA. The MRA protocol included
      both 2D inflow angiography and 3D phase-contrast angiography. Surgery was carried
      out in 13 patients. The image quality of MRA was judged satisfactory in all
      cases. The findings with respect to vascular involvement agreed between the
      radiological methods in all but 3 cases. When the findings were correlated with
      the final diagnosis, one false-negative case was found for each of the three
      methods. The results suggest that MRI with MRA, including both the phase-contrast
      and inflow techniques, has a similar diagnostic value to that of conventional
      angiography and ultrasonography in the preoperative assessment of the portal
      venous system in patients with pancreatic carcinoma. Further studies are needed
      to establish the optimal diagnostic procedure.

PMID- 9166561
TI  - Pseudotumoral presentation of nodular regenerative hyperplasia of the liver:
      imaging in five patients including MR imaging.
AB  - Nodular regenerative hyperplasia (NRH) of the liver is a condition characterized
      by multiple monoacinar regenerative nodules in the absence of fibrous septa. When
      these nodules become confluent they may be seen with sonography or CT. The
      appearance of these pseudotumoral pattern of NRH has been scarcely described with
      MRI. We present the imaging findings of five patients with NRH and a
      pseudotumoral form at sonography. Sonography depicted hyperechoic lesions in four
      patients and hypoechoic lesions in another. Computed tomography showed hypodense
      lesions with little contrast enhancement in two patients. Three patients showed
      subtle focal liver lesions on MRI: isointense in one, mildly hypointense in
      another, and minimally hyperintense in a patient with siderosis. The dynamic
      behavior at MRI was similar to the normal liver parenchyma. Hyperechoic lesions
      on sonography or hypodense lesions on CT, barely or not seen on MRI, can be
      indicative of NRH in an appropriate clinical setting.

PMID- 9166562
TI  - Hydro-CT in patients with gastric cancer: preoperative radiologic staging.
AB  - A total of 35 patients (age range 35-78 years) with gastric tumors on the lesser
      curve, or in the antro-pyloric region, underwent angio-CT in the prone position
      after filling the stomach with 500 ml of water and intravenous administration of
      glucagon. The films were reviewed by three radiologists independently, staging
      each tumor according to the TNM classification preoperatively. The overall
      accuracy of tumor staging ranged between 66-77 %, overstaging between 17-25 %,
      and understaging between 3-8.5 %. The diagnostic sensitivity, specificity, and
      accuracy for serosal invasion ranged between 90 and 100, 76 and 84, and 80-88 %,
      respectively, and the overall accuracy for N staging was 46, 48, and 51 % for the
      three observers. If, however, N1 and N2 tumors were considered as a single group,
      N-stage accuracy increased, ranging between 63 and 77 %. The "K test" for
      analyzing the interobserver agreement was 60 %, i. e., the diagnostic results are
      reproducible. Water filling of the stomach optimizes visualization of the gastric
      wall on contrast-enhanced CT. The prone position and drug-induced hypotony allows
      for good distension without any disturbing artifact reduction obscuring the lower
      gastric body.

PMID- 9166563
TI  - Lymphoproliferative disorders in organ transplant recipients.

PMID- 9166564
TI  - Differential diagnosis of scrotal masses by ultrasound.
AB  - Ultrasound is the mainstay for imaging of the scrotum. It is used primarily for
      determining the location and nature of palpable lesions and to demonstrate
      nonpalpable lesions. Scrotal US is characterized by high sensitivity in the
      detection of intrascrotal abnormalities and is a very good mode for
      differentiating testicular from paratesticular lesions. However, scrotal US is
      limited in determining whether a focal testicular lesion is benign or malignant.
      The limitations of gray-scale US in the assessment of an acute scrotum and in
      particular of testicular torsion have now been overcome by color-coded duplex
      sonography and power Doppler.

PMID- 9166565
TI  - Non-contrast spiral CT for patients with suspected renal colic.
AB  - Renal colic, defined as acute flank pain caused by the passage of a ureteral
      calculus, is a common condition, but the correct diagnosis may not be apparent
      clinically. For decades, intravenous urography has been the test of choice for
      evaluating patients with suspected renal colic. Recently, unenhanced (non
      contrast) helical CT has been shown to be an accurate and highly effective
      examination which can be used instead of intravenous urography. In this article,
      the technique is reviewed in detail, including its advantages and potential
      pitfalls.

PMID- 9166566
TI  - CT evaluation of underlying cause in spontaneous subcapsular and perirenal
      hemorrhage.
AB  - We evaluated the CT scans of 13 patients with spontaneous subcapsular or
      perinephric hemorrhage (SPH) associated with these underlying causes: 4
      angiomyolipomas, 2 renal cell carcinomas, 1 renal metastatic malignant melanoma,
      1 ruptured renal artery aneurysm, 1 adrenal myelolipoma, 1 ruptured renal
      abscess, 2 ruptured hemorrhagic cysts, and 1 patient with undiagnosed coagulation
      disorder. Our objective was to ascertain whether an underlying cause of SPH was
      identifiable by CT, and to determine the extension of the hematomas. Computed
      tomography identified the hematoma in all 13 cases (sensitivity 100 %). In all 12
      cases in which there was a renal or adrenal anatomic lesion, the underlying cause
      was identified with CT (100 %), with correct diagnosis in 11 cases (91.6 %). The
      case in which no lesion was identified was the undiagnosed coagulation disorder.
      We conclude that CT is a useful technique for the initial evaluation of SPH,
      permitting diagnosis of hemorrhage and identification of the underlying cause.

PMID- 9166567
TI  - Adrenal cavernous hemangioma: MRI, CT, and US appearance.
AB  - Two cases of rare adrenal cavernous hemangiomas are reported, one imaged with
      conventional X-ray techniques, US, CT, and MRI, and the other with US and CT. The
      CT technique clearly demonstrated calcifications and the internal structure of
      the lesions in both cases and peripheral rim enhancement on the postcontrast scan
      in one patient. Although MRI demonstrated accurately the complex nature of the
      lesion, the inability to visualize the calcified areas do not allow to make a
      specific histologic diagnosis.

PMID- 9166568
TI  - Follow-up of aortic dissection: contribution of MR angiography for evaluation of
      the abdominal aorta and its branches.
AB  - Spin-echo MR is an established method to evaluate thoracic aortic dissections,
      but is not well suited to study the abdominal aorta. In this study we evaluated
      whether MR angiography could provide a complete examination of the abdominal
      aorta. In 28 patients (40 MR studies) with suspected (n = 6) or known (n = 34)
      aortic dissection, MR studies were performed. Thoracic aorta was evaluated with
      spin-echo and gradient-recalled-echo MR imaging. Axial two-dimensional time-of
      flight MR angiography with thin overlapping slices was used to study the
      abdominal aorta. Intermediate and high signal intensity on MR angiography was
      interpreted as patent flow, and low signal was interpreted as thrombus. The
      presence of an intima flap and the re-entry site could be depicted in all MR
      studies. Thrombus in the false channel was seen in 8 studies. The origin of the
      abdominal visceral branches and their relation to the false-true channel could be
      depicted, except in 4 of 80 renal arteries studied. Extension of the dissection
      into the coeliac trunk was seen in 2 and in the superior mesenteric artery in 10
      studies. Dilatation of the suprarenal abdominal aorta was seen in 20 studies, and
      of the infrarenal aorta in 9 studies. MR angiography provides valuable
      information about the abdominal aorta and its branches in patients with aortic
      dissection. This makes MR imaging appealing as the preferred imaging modality for
      the diagnosis and follow-up of aortic dissection.

PMID- 9166569
TI  - Juxtarenal aortic aneurysm: endoluminal transfemoral repair?
AB  - Endoluminal transfemoral repair of an abdominal aortic aneurysm by a stent graft
      placement requires a segment of the nondilated infrarenal aorta of at least 15 mm
      long for safe stent graft attachment. The possibility of endoluminal treatment of
      a juxtarenal abdominal aortic aneurysm with partially covered spiral Z stent was
      assessed in experiment and in three clinical cases. In the experiment, the
      noncovered spiral Z stent was placed into the abdominal aorta, across the origins
      of renal arteries and mesenteric arteries, in six dogs. In the clinical cases, a
      partially covered stent graft was attached in 3 patients with the juxtarenal
      abdominal aortic aneurysm (of the group of 12 patients with abdominal aortic
      aneurysm). The stent grafts were attached with proximal uncovered parts across
      the origins of the renal arteries. In experiment, the renal artery occlusions or
      stenoses were not observed 36 months after stent placement, and in clinic, 3
      patients with the juxtarenal aortic aneurysm were successfully treated by stent
      graft placement. There were no signs of flow impairment into the renal arteries
      14 months after stent graft implantation. This approach can possibly expand the
      indications for endoluminal grafting in the treatment of juxtarenal aortic
      aneurysms in patients who are at high risk for surgery.

PMID- 9166571
TI  - Spiral CT findings in a case of pulmonary sequestration.
AB  - Pulmonary sequestration has always been diagnosed by direct demonstration of the
      vessels tributary to the lesion, usually by angiography. Conventional CT can
      identify the arterial supply in only two thirds of cases. We report a case of
      pulmonary sequestration diagnosed using Spiral CT, based on the demonstration of
      both arterial supply and venous drainage. The capabilities of Spiral CT to detect
      subtle vessel abnormalities and to yield reliable multiplanar imaging enabled us
      to show the whole course of both the artery and the vein tributary to the lesion.
      Axial images were the most useful ones to diagnose pulmonary sequestration; 2D
      and 3D reconstructions were useful for a detailed and immediate spatial depiction
      of the parenchymal abnormality and of its vascular pedicle.

PMID- 9166570
TI  - Thoracic complications in uremic patients and in patients undergoing dialytic
      treatment: state of the art.
AB  - No organ in the chest is spared the negative effects of uremia. The dialytic
      treatment itself is often associated with a large array of thoracic
      complications. We review the main thoracic manifestations of the terminal uremia
      from the radiological point of view, such as: uremic pleuritis and pericarditis,
      uremic pneumonia, renal osteodystrophy, infections, and metastatic pulmonary
      calcifications. Respiratory function derangement and the problems related to
      peritoneal dialysis and hemodialysis are discussed in some detail, along with the
      diagnostic role of plain films, US, nuclear medicine, and CT. The main focus of
      this review is on the hydration problems and pulmonary edema, often related to a
      large number of pathogenetic factors. Based on our experience, we think that the
      chest X-ray is not able to accurately discriminate between cardiogenic edema and
      fluid overload edema (so-called renal pulmonary edema). The radiological findings
      of the thoracic complications in uremic patients are multiple and complex but, in
      most cases, the imaging techniques may offer an accurate and noninvasive
      diagnostic approach, with a high benefit-cost ratio.

PMID- 9166572
TI  - US imaging and color Doppler in patients undergoing inhibitory therapy with
      calcitriol for secondary hyperparathyroidism.
AB  - The aim of this study was to evaluate the changes in volume, structure, and flow
      pattern of parathyroid glands in uremic patients with secondary
      hyperparathyroidism treated with long-term intravenous calcitriol (CTL) therapy.
      Ultrasonography was used to follow-up volume changes occurring in 18 enlarged
      glands in 11 patients during an 18-month period; in 6 of these cases, 11 glands
      were followed-up also with color-Doppler to monitor variations in flow pattern.
      Vascularization was classified using three grades: grade 0 = no color signal;
      grade I = vessels covering less than 50 % of glandular cross-sectional area;
      grade II = vascular signals covering more than 50 % of glandular cross-sectional
      area. No significant changes in volume were demonstrated during the 18 months of
      follow-up. On the contrary, significant decrease in flow was observed with almost
      complete disappearance of color-Doppler signals. This finding related well with
      the observed decrease in parathormone blood levels. Lack of volume changes during
      medical therapy demonstrates the inability of US alone to monitor the effect of
      this treatment on the parathyroid glands. Conversely, the observed intraglandular
      flow reduction indicates the possibility to use color Doppler to monitor the
      effects of CLT in uremic hemodialyzed patients with secondary
      hyperparathyroidism. This imaging procedure can be proposed for follow-up of the
      response of the parathyroid glands to therapy.

PMID- 9166573
TI  - MR imaging in retinoblastoma.
AB  - We studied the appearance of retinoblastoma on unenhanced and gadolinium-enhanced
      images and the accuracy of tumour staging with MR imaging. The MR images were
      obtained in 18 children with retinoblastoma and compared with histopathological
      findings after enucleation. The MR imaging included T1-weighted and dual-echo T2
      weighted images before, and T1-weighted images after, gadopentetate dimeglumine
      injection. The contrast between tumour and ipsilateral vitreous strongly
      increased (57 %) after gadolinium on T1-weighted images (p = 0.004). Tumour was
      strongly hypointense as compared with ipsilateral vitreous in all patients using
      heavily T2-weighted (TE = 120 ms) images (p = 0.001). The estimated T2 of tumour
      (mean 96 + 14 ms) did not correlate with histological grading or degree of
      calcification. Unenhanced T1-weighted MR images rightfully excluded extrascleral
      growth in 16 of 16 cases, but its presence was confirmed after enucleation in
      only one of 2 abnormal MR scans. Invasion of the optic nerve behind the
      cribriform plate was confirmed in 2 of 3 abnormal gadolinium-enhanced MR scans,
      but also in 1 of the 15 cases in which MR images were normal. The T2-weighted
      images were useful in assessing retinal detachment. We conclude that heavily T2
      weighted images, unenhanced T1-weighted images and gadolinium-enhanced T1
      weighted MR images are complementary in characterizing and staging
      retinoblastoma.

PMID- 9166575
TI  - Three-dimensional MR myelography of the lumbar spine: comparative case study to X
      ray myelography.
AB  - Conventional myelography was compared with a new type of MR technique using a fat
      suppressing 3D fast imaging with steady precession (FISP) sequence for diagnosis
      of the lumbar root compression syndrome. 80 patients with discogenic disease in
      the lumbar spine were examined with a 1.0-T whole-body MR system (Siemens
      Magnetom Impact, Erlangen, Germany). A strongly T2(*)-weighted 3D FISP sequence
      was applied in the sagittal orientation. To obtain fat suppression, a frequency
      selective 1-3-3-1 prepulse was applied prior to the imaging sequence. The
      acquired 3D data set was evaluated using a maximum intensity projection (MIP)
      program. The measurement time was 7 min, 47 s. Magnetic resonance myelography has
      significant advantages over conventional myelography, particularly in cases of
      extreme spinal canal stenosis. Compared with the conventional method, this new MR
      technique shows comparable sensitivity in the visualization of the spinal nerve
      roots in the lumbar spine.

PMID- 9166574
TI  - MRI diagnosis of intramedullary metastases from extra-CNS tumors.
AB  - The purpose of this study was to evaluate the topography, morphology and contrast
      enhancement of the intramedullary metastases (IM) from extra-CNS neoplasms. We
      report the results of a multicenter retrospective study on 18 patients with 26 IM
      examined with a 0.5T MR imaging system; intravenous injection of Gd-DTPA was
      performed in all cases. We found that the lesions are most frequently single,
      oval shaped, and small, with little or no deformation of the spinal cord (14 of
      26 IM). They appear isointense on spin-echo T1-weighted images (24 of 26 IM),
      with a homogeneous and generally nodular high contrast enhancement after Gd-DTPA
      injection (21 of 26 IM), and present on T2- and proton-density-weighted sequences
      with a pronounced perilesional, pencil-shaped hyperintensity of the surrounding
      cord which is more evident in the cranial part of the cord referring to the IM.

PMID- 9166576
TI  - Computer-assisted reading of mammograms.
AB  - Techniques developed in computer vision and automated pattern recognition can be
      applied to assist radiologists in reading mammograms. With the introduction of
      direct digital mammography this will become a feasible approach. A radiologist in
      breast cancer screening can use findings of the computer as a second opinion, or
      as a pointer to suspicious regions. This may increase the sensitivity and
      specificity of screening programs, and it may avoid the need for double reading.
      In this paper methods which have been developed for automated detection of
      mammographic abnormalities are reviewed. Programs for detecting
      microcalcification clusters and stellate lesions have reached a level of
      performance which makes application in practice viable. Current programs for
      recognition of masses and asymmetry perform less well. Large-scale studies still
      have to demonstrate if radiologists in a screening situation can deal with the
      relatively large number of false positives which are marked by computer programs,
      where the number of normal cases is much higher than in observer experiments
      conducted thus far.

PMID- 9166578
TI  - Radiology in Finland.

PMID- 9166577
TI  - Mammographic changes in postmenopausal women on hormonal replacement therapy.
AB  - The purpose of this study was to investigate the extent of the effects of
      hormonal replacement therapy (HRT) on the mammographic breast pattern in
      postmenopausal women. In a hospital-based study mammographic examinations of 81
      postmenopausal women were evaluated retrospectively, before and after 1-2 years
      of treatment with oestrogens or a combination of oestrogens and progestagens.
      Each individual mammographic film was examined separately, and the glandular
      tissue was classified according to a modified Wolfe classification. In a
      screening-centre-based study two consecutive mammograms, with a 2-year interval,
      of 645 women, of whom 70 were using some kind of hormone therapy, were evaluated
      retrospectively. In the hospital-based study 31 % of patients treated with
      combination HRT showed an increase in fibroglandular tissue compared with only
      8.7 % in the group treated with oestrogens alone. The difference was
      statistically significant (p = 0.046). In the screening-based study 14.3 % of the
      women using hormonal therapy showed an increase, whereas in the non-users no
      increase was found (p = 1.24 x 10(-10)). After beginning HRT many women (between
      14 and 25 % in our experience) can be expected to undergo a mammographically
      detectable increase in fibroglandular tissue. Radiologists should be aware of the
      aetiology of such changes, and can obtain information on HRT most conveniently by
      having the technologist routinely question each patient.

PMID- 9166579
TI  - Mapping genes controlling hematocrit in the spontaneously hypertensive rat.
AB  - The genes that determine the baseline hematocrit level in humans and experimental
      animals are unknown. The spontaneously hypertensive rat (SHR), the most widely
      used animal model of human essential hypertension, exhibits an increased
      hematocrit when compared with the normotensive Brown Norway (BN-Lx) strain (0.54
      +/- 0.02 vs. 0.44 +/- 0.02, p < 0.01). Distribution of hematocrit values among
      recombinant inbred (RI) strains derived from SHR and BN-Lx progenitors was
      continuous, which suggests a polygenic mode of inheritance. The narrow
      heritability of the hematocrit was estimated to be 0.32. The Eno2 marker on
      Chromosome (Chr) 4 showed the strongest association (p < 0.0001) with the
      observed variability of hematocrit among RI strains. The erythropoietin (Epo)
      gene, originally reported to be syntenic with Eno2, has been mapped to Chr 12,
      thus excluding it as a potential candidate gene for the increased hematocrit in
      the SHR. The current linkage data extend homologies between rat, mouse, and human
      chromosomes.

PMID- 9166580
TI  - Genealogy of the 129 inbred strains: 129/SvJ is a contaminated inbred strain.
AB  - The 129 mouse is the most widely used strain in gene targeting experiments.
      However, numerous substrains exist with demonstrable physiological differences.
      In this study a set of simple sequence length polymorphisms (SSLPs) was used to
      determine the relatedness of selected 129 substrains. 129/SvJ was significantly
      different from the other 129 substrains and is more accurately classified as a
      recombinant congenic strain (129cX/Sv), being derived from 129/Sv and an unknown
      strain. This mixed genetic background could complicate gene targeting experiments
      by reducing homologous recombination efficiency when constructs and ES cells are
      not derived from the same 129 substrain. Additionally, discrepancies due to
      different genetic backgrounds may arise when comparing phenotypes of genes
      targeted in different 129-derived ES cell lines.

PMID- 9166581
TI  - The mouse homolog of FRG1, a candidate gene for FSHD, maps proximal to the
      myodystrophy mutation on chromosome 8.
AB  - The human autosomal dominant neuromuscular disorder facioscapulohumeral muscular
      dystrophy (FSHD) is associated with deletions within a complex tandem DNA repeat
      (D4Z4) on Chromosome (Chr) 4q35. The molecular mechanism underlying this
      association of FSHD with DNA rearrangements is unknown, and, thus far, no gene
      has been identified within the repeat. We isolated a gene mapping 100 kb proximal
      to D4Z4 (FSHD Region Gene 1:FRG1), but were unable to detect any alterations in
      total or allele-specific mRNA levels of FRG1 in FSHD patients. Human Chr 4q35
      exhibits synteny homology with the region of mouse Chr 8 containing the gene for
      the myodystrophy mutation (myd), a possible mouse homolog of FSHD. We report the
      cloning of the mouse gene (Frg1) and show that it maps to mouse Chr 8. Using a
      cross segregating the myd mutation and the European Collaborative Interspecific
      Backcross, we showed that Frg1 maps proximal to the myd locus and to the Clc3 and
      Ant1 genes.

PMID- 9166582
TI  - Mapping and retinal phenotype of the hugger mutation in the mouse.
AB  - Hugger, hug, is a recessively expressed mutation in mice that features mildly
      abnormal locomotion, not yet explained, and a unique combination of developmental
      and degenerative retinal abnormalities. Analysis with the efficient MEV linkage
      testing stock established that hug is on mouse Chr 19 about 14 cM from th
      centromere, between the microsatellite markers D19Mit28 and D19Mit14. An abnormal
      retinal phenotype was recognized on the day of birth, when some retinal ganglion
      cells already lie in abnormal positions in the inner plexiform layer. By
      postnatal day 18 the number of neurons is reduced in all three cellular layers of
      the retina. Rod photoreceptor cells develop only rudimentory outer segments, and
      by 9 months of age, about 75% of the photoreceptor cells have completely
      disappeared. Similar photoreceptor cell abnormalities are seen in prph2 (formerly
      rds) homozygotes, which lack the peripherin/rds protein of the rod outer
      segments, but a mating of the respective homozygotes yielded normal progeny.
      Rom1, which codes for an outer segment protein similar to peripherin/rds, maps to
      a more proximal position on Chr 19.

PMID- 9166583
TI  - The mouse Cat4 locus maps to chromosome 8 and mutants express lens-corneal
      adhesion.
AB  - Cat4 is the second largest allelism group in the collection of mouse dominant eye
      mutations recovered in Neuherberg and carriers express anterior polar cataract,
      central corneal opacity, and lens-corneal adhesions. We have mapped the Cat4
      locus of the mouse to central Chromosome (Chr) 8 at position cM 31. Histological
      characterization of Cat4(a) heterozygotes and homozygotes indicates failure of
      separation of the lens vesicle from the surface ectoderm. Human anterior segment
      ocular dysgenesis (ASOD) is autosomal dominant, carriers express an eye phenotype
      similar to that of Cat4(a) carriers, and it has been mapped to a region of 4q
      homologous to mouse central Chr 8. Thus, on the basis of phenotype and map
      position, Cat4 may be a mouse model of human ASOD. The genes Junb, Jund1, Mel,
      and Zfp42 are discussed as possible candidates for Cat4.

PMID- 9166584
TI  - A serine-to-proline mutation in the copper-transporting P-type ATPase gene of the
      macular mouse.
AB  - We have investigated the cDNA sequence of the copper-transporting P-type ATPase
      (Atp7a) gene of the macular mouse, a model for human Menkes disease. A point
      mutation (T to C) that results in substitution of proline for serine in a
      putative eighth transmembrane domain of the ATP7A was identified. This contrasts
      with abnormalities identified in the Atp7a of other mottled mouse strains: lack
      of expression of Atp7a mRNA in the dappled mouse, and a splicing mutation in the
      blotchy mouse.

PMID- 9166586
TI  - Comparative chromosome painting between two marsupials: origins of an XX/XY1Y2
      sex chromosome system.
AB  - Cross-species chromosome painting was used to investigate genome rearrangements
      between tammar wallaby Macropus eugenii (2n = 16) and the swamp wallaby Wallabia
      bicolor (2n = 10female symbol/11male symbol), which diverged about 6 million
      years ago. The swamp wallaby has an XX female:XY1Y2 male sex chromosome system
      thought to have resulted from a fusion between an autosome and the small original
      X, not involving the Y. Thus, the small Y1 should represent the original Y and
      the large Y2 the original autosome. DNA paints were prepared from flow-sorted and
      microdissected chromosomes from the tammar wallaby. Painting swamp wallaby
      spreads with each tammar chromosome-specific probe gave extremely strong and
      clear signals in single-, two-, and three-color FISH. These showed that two
      tammar wallaby autosomes are represented unchanged in the swamp wallaby, two are
      represented by different centric fusions, and one by a tandem fusion to make the
      very long arms of swamp wallaby Chromosome (Chr) 1. The large swamp wallaby X
      comprises the tammar X as its short arm, and a tandemly fused 7 and 2 as the long
      arm. The acrocentric swamp wallaby Y2 is a 2/7 fusion, homologous with the long
      arm of the X. The small swamp wallaby Y1 is confirmed as the original Y by its
      painting with the tammar Y. However, the presence of sequences shared between the
      microdissected tammar Xp and Y on the swamp wallaby Y2 implies that the formation
      of the compound sex chromosomes involved addition of autosome(s) to both the
      original X and Y. We propose that this involved fusion with an ancient
      pseudoautosomal region followed by fission proximal to this shared region.

PMID- 9166585
TI  - An interstitial telomere array proximal to the distal telomere of mouse
      chromosome 13.
AB  - Lambda clones of mouse DNA from BALB/c and C57BL/10, each containing an array of
      telomere hexamers, were localized by FISH to a region close to the telomere of
      Chr 13. Amplification of mouse genomic DNA with primers flanking SSRs within the
      cloned DNA showed several alleles, which were used to type eight sets of RI
      strains. The two lambda clones contained allelic versions of the interstitial
      telomere array, Tel-rs4, which is 495 bp in C57BL/10 and which includes a variety
      of sequence changes from the consensus telomere hexamer. Comparison of the
      segregation of the amplification products of the SSRs with the segregation of
      other loci in an interspecies backcross (C57BL/6JEi x SPRET/Ei) F1 x SPRET/Ei
      shows recombination suppression, possibly associated with ribosomal DNA sequences
      present on distal Chr 13 in Mus spretus, when compared with recombination in an
      interstrain backcross, (C57BL/6J x DBA/J) F1 x C57BL/6J, and with the MIT F2
      intercross. Analysis of recombination in females using a second interstrain
      backcross, (ICR/Ha x C57BL/6Ha) F1 x C57BL/6Ha, also indicates recombination
      suppression when compared with recombination in males of the same strains, using
      backcross C57BL/6Ha x (ICR/Ha x C57BL/6Ha) F1. Thus, more than one cause may
      contribute to recombination suppression in this region. The combined order of the
      loci typed was D13Mit37-D13Mit30-D13Mit148-(D13Rp1, 2, 3, 4, Tel-rs4)-D13Mit53
      D13Mit196-D13Mit77-(D13Mit7 8, 35). Data from crosses where apparently normal
      frequencies of recombination occur suggest that the telomere array is about 6 map
      units proximal to the most distal loci on Chr 13. This distance is consistent
      with evidence from markers identified in two YAC clones obtained from the region.

PMID- 9166588
TI  - Physical assignment of glucagon and nebulin in cattle, sheep, and goat.

PMID- 9166587
TI  - Mapping of 22 expressed sequence tags isolated from a porcine small intestine
      cDNA library.
AB  - Complementary DNA sequences were selected from a resource of tentatively
      identified clones from a porcine small intestine cDNA library. Forty PCR primer
      pairs were designed to amplify 101-309 base pairs of the 3' untranslated region
      of the genes. The PCR conditions were optimized by altering both formamide and
      magnesium concentrations on samples of pig, mouse, and hamster DNA. Twenty primer
      pairs that, under stringent conditions, were pig-specific and amplified the
      expected fragments were chosen for regional assignment in a pig/rodent hybrid
      cell panel. Furthermore, 22 primer pairs were chosen to amplify DNA from the
      parental animals of the PiGMaP shared reference families in order to detect
      possible polymorphisms. Primer pairs that generated polymorphisms were used for
      genetic mapping. A total of 22 porcine expressed sequence tags (ESTs) were
      cytogenetically or genetically mapped by this approach. Twelve of the mapped ESTs
      could be added to the human-porcine comparative map.

PMID- 9166589
TI  - Towards interbreed IBD fine mapping of the mh locus: double-muscling in the
      Asturiana de los Valles breed involves the same locus as in the Belgian Blue
      cattle breed.
AB  - The Spanish "Asturiana" cattle breed is characterized by the segregation of a
      genetically determined muscular hypertrophy referred to as double-muscling or
      "culones". We demonstrate by linkage analysis that this muscular hypertrophy
      involves the mh locus previously shown to cause double-muscling in the Belgian
      Blue cattle breed, pointing towards locus homogeneity of this trait across both
      breeds. Moreover, using a twopoint and multipoint maximum likelihood approach, we
      show that flanking microsatellite markers are in linkage disequilibrium with the
      mh locus in both breeds albeit with different alleles. Finally, we discuss how
      allelic homogeneity across breeds might be exploited to achieve efficient genetic
      fine-mapping of the mh locus.

PMID- 9166590
TI  - Gene homologs on human chromosome 15q21-q26 and a chicken microchromosome
      identify a new conserved segment.
AB  - The genes for insulin-like growth factor 1 receptor (IGF1R), aggrecan (AGC1),
      beta2-microglobulin (B2M), and an H6-related gene have been mapped to a single
      chicken microchromosome by genetic linkage analysis. In addition, a second H6
      related gene was mapped to chicken macrochromosome 3. The Igf1r and Agc1 loci are
      syntenic on mouse Chr 7, together with Hmx3, an H6-like locus. This suggests that
      the H6-related locus, which maps to the chicken microchromosome in this study, is
      the homolog of mouse Hmx3. The IGF1R, AGC1, and B2M loci are located on human Chr
      15, probably in the same order as found for this chicken microchromosome. This
      conserved segment, however, is not entirely conserved in the mouse and is split
      between Chr 7 (Igf1r-Agc) and 2 (B2m). This comparison also predicts that the
      HMX3 locus may map to the short arm of human Chr 15. The conserved segment
      defined by the IGF1R-AGC1-HMX3-B2M loci is approximately 21-35 Mb in length and
      probably covers the entire chicken microchromosome. These results suggest that a
      segment of human Chr 15 has been conserved as a chicken microchromosome. The
      significance of this result is discussed with reference to the evolution of the
      avian and mammalian genomes.

PMID- 9166591
TI  - SSLPs to map genetic differences between the 129 inbred strains and closed
      colony, random-bred CD-1 mice.

PMID- 9166592
TI  - Sequence and chromosomal mapping of the mouse homolog (Madh4) of the human
      DPC4/MADH4 gene.

PMID- 9166593
TI  - Leptin receptor mutations in 129 db3J/db3J mice and NIH facp/facp rats.

PMID- 9166594
TI  - Genomic organization of the human integrin beta4 gene.

PMID- 9166595
TI  - Genetic mapping of the vascular endothelial growth factor (Vegf) gene to mouse
      chromosome 17.

PMID- 9166596
TI  - The gene encoding the transcription factor Spi-B maps to mouse chromosome 7.

PMID- 9166597
TI  - The gene encoding the heart/muscle isoform of cytochrome c oxidase subunit VIII
      maps to mouse chromosome 7.

PMID- 9166599
TI  - Linkage mapping of the cellular retinoic acid-binding protein 1 (Crabp1) gene to
      rat chromosome 8.

PMID- 9166598
TI  - Linkage mapping of rat Rb1 gene on chromosome 15.

PMID- 9166600
TI  - Assignment of the porcine nuclear factor I/CTF (NFI/CTF) gene to chromosome 2q12
      13 by FISH.

PMID- 9166601
TI  - Assignment of ARAF1 to porcine chromosome Xp11.2-p13 by fluorescence in situ
      hybridization.

PMID- 9166602
TI  - Novel conserved synteny between human chromosome 22 and cattle chromosome 22
      established by linkage mapping of transducin alpha-1 subunit (GNAZ).

PMID- 9166603
TI  - Construction of a large-insert yeast artificial chromosome library of the rat
      genome

PMID- 9166606
TI  - Dermatologic problems in the elderly.
AB  - Age-related skin changes place older adults at risk for a variety of dermatologic
      problems, ranging from xerosis, or dry skin, to malignant melanoma, a life
      threatening condition. Primary care providers must differentiate rashes caused by
      fungal infections, eczematous conditions, viral infections, drug reactions, and
      other common causes in this age group. Providers should be familiar with
      dermatologic therapy that may involve topical preparations, oral medications, and
      surgical methods. In addition, patient education about symptom treatments, skin
      hygiene, and preventive measures can greatly improve the clinical condition and
      quality of life of older adults.

PMID- 9166605
TI  - Scaling skin disorders.
AB  - Scaling skin disorders have similar features. Careful inspection to determine the
      characteristics of the primary lesion, along with distribution patterns and
      performance of routine diagnostic tests, usually lead to a correct diagnosis.
      Potassium hydroxide examination should be performed on most scaling skin
      disorders. If a microscope is not readily available, skin scrapings should be
      sent to a microbiology laboratory, or a microscope should be purchased and
      training obtained. A binocular microscope is preferable to view fungal hyphae.
      KOH examination requires supervised experience to become proficient.

PMID- 9166607
TI  - Granuloma annulare. A clinical review.
AB  - Granuloma annulare is a self-limiting disorder occurring primarily in children.
      The clinician must recognize clinical variants, including localized,
      subcutaneous, disseminated, and perforating granuloma annulare. Although
      granuloma annulare can rarely be associated with underlying systemic disease, in
      most patients the eruption resolves without treatment in several months to
      several years. Patients and families should be counseled accordingly.

PMID- 9166608
TI  - Office management of minor burns.
AB  - About 2 million people are burned in the United States each year. About 80% of
      these are treated as outpatients. Flame burns are the most common type of burn
      injury in adults, and scald burns are the primary type in children. Primary care
      providers must be familiar with burn assessment so burn injuries can be triaged
      appropriately to a regional burn center, an acute care (facility, or office
      management. Assessment includes extent and depth of burns, location of burns,
      patient reliability, and the home situation. Office management involves emergency
      care, debridement and dressings, topical antimicrobials, and pain control.
      Patient education for care in the home environment is essential for optimal
      healing.

PMID- 9166609
TI  - Dermatologic manifestations of human immunodeficiency virus disease.
AB  - The skin may be the most commonly affected organ in patients with human
      immunodeficiency virus disease. As the body's natural immune mechanism
      deteriorates, susceptibility to bacterial, fungal, viral, and parasitic agents
      increases. This may be manifested in a variety of ways, ranging from pruritus and
      generalized xerosis to severe infections with opportunistic agents. It is
      important that all clinicians be aware of the dermatologic manifestations of the
      infection, because inspection may lead to early diagnosis of human
      immunodeficiency virus disease or early recognition of a life-threatening
      illness.

PMID- 9166610
TI  - Topical corticosteroid therapy. Considerations for prescribing and use.
AB  - Several points should be considered when one is prescribing topical
      corticosteroids: The correct assessment of the underlying skin condition. A good
      understanding of the action of the active ingredients. Knowledge of different
      drug vehicles and proper application methods. Adequate patient education of
      correct usage and potential side effects. When health care providers and patients
      are aware of the use and misuse of topical corticosteroids, the agents can safely
      be prescribed with beneficial results.

PMID- 9166611
TI  - Acne treatment. A comprehensive review of pharmacotherapy.

PMID- 9166612
TI  - Acne vulgaris.

PMID- 9166613
TI  - Lice and scabies.

PMID- 9166614
TI  - Contact dermatitis.

PMID- 9166615
TI  - Common warts.

PMID- 9166616
TI  - Skin cancer screening and skin self-examination.

PMID- 9166617
TI  - Lice and scabies treatment.

PMID- 9166618
TI  - Surgical wounds.

PMID- 9166619
TI  - Patient with acute onset of vesicular rash.

PMID- 9166620
TI  - Allergic diseases.

PMID- 9166621
TI  - Differential diagnosis. Rhinitis.

PMID- 9166622
TI  - Latex allergy.
AB  - Latex allergy and hypersensitivity are becoming major health concerns and
      occupational risks for health care workers. An allergic reaction can be immediate
      or delayed. Manifestations are either localized-cell mediated (type IV)-or
      systemic-IgE mediated (type I). The primary populations at risk are children with
      spina bifida, health care workers, people with atopic allergies, and those with a
      history of multiple surgeries. This new health care problem may be linked to the
      increased use of latex gloves and to changes in the manufacturing of gloves to
      meet the demand. The care of hypersensitive patients is a challenge for health
      care providers, since natural rubber latex is present in more than 40,000
      products.

PMID- 9166623
TI  - Food allergy.
AB  - Food allergy is an immunologically mediated hypersensitivity reaction that occurs
      in 1% to 2% of the general population and in about 8% of children. Reactions
      mediated by IgE antibodies are the most common type of food allergy and can cause
      asthma, rhinitis, atopic dermatitis, urticaria, and anaphylaxis, which can be
      lethal. A proper diagnosis can be established through a careful history and
      physical examination, tests for IgE antibodies specific for food antigens, a
      favorable response to an allergen elimination diet, and, if necessary, blinded
      and controlled allergen challenge. The only effective therapy is avoidance of the
      problem foods. Resolution of the sensitivity over time is more common in younger
      patients than in adults and for some foods more than others. Most adverse food
      reactions are due to nonimmunologic intolerance and can be managed differently.

PMID- 9166624
TI  - Otitis media with effusion.
AB  - Otitis media with effusion is common in young children and varies widely in
      duration and severity. Defined as fluid in the middle ear without signs or
      symptoms of infection, it is generally asymptomatic. However, it has the
      potential to adversely affect hearing, speech development, and language
      acquisition.

PMID- 9166625
TI  - Urticaria and angioedema. A simple approach to a complex problem.
AB  - Urticaria is a complex problem for both primary care practitioners and patients.
      Patients often present in considerable distress, with pruritus and uncomfortable
      lesions. They are frightened and frustrated about their condition and are
      searching for answers. Attempting to identify the cause by evaluating patient
      medications, contacts, and dietary history can be challenging. A multitude of
      laboratory tests can be performed, but they often do not provide a diagnosis.
      Skin allergy testing is frequently difficult at this stage. A working knowledge
      of the underlying pathology and causes of urticaria is essential during
      diagnosis. Astute evaluation can provide the clues necessary to accurately
      identify and treat the problem with available medications and modalities.

PMID- 9166626
TI  - Chronic recurrent sinusitis. Recognition and treatment.
AB  - Chronic recurrent sinusitis is associated with a reduced nasal passage at the
      middle turbinate and through the sinus ostia secondary to inflammation,
      structural abnormality, or increased mucus production. Adversely affecting the
      quality of life of many people, this common disorder can challenge the primary
      health care provider. Problems such as recognition of the disorder and adequate
      treatment are complicated by the lack of universal definition, absence of
      preventive measures, and dearth of clear end-point definitions for successful
      therapy. The myriad of symptoms makes the recognition and treatment of the
      disorder particularly complex.

PMID- 9166627
TI  - Adherence issues in clinical practice.
AB  - To combat the millions of days of restricted activity and the billions of dollars
      spent in respiratory clinical practice, national health objectives are targeting
      people with asthma. Research data depict nurses and other health care providers
      as encountering patients with asthma and allergies who do not adhere to their
      medical and nursing care management plans. The skills and success with which
      these professional caregivers are able to assist these patients depends on an
      understanding of how to measure and evaluate compliance and adherence issues. In
      turn, this implementation of effective strategies for optimal patient outcomes
      can be actualized. Patient-related, practice-related, and health care provider
      related factors must be considered to ensure that patients get the best chance to
      succeed and to be compliant. Achieving adherence with regimens not only reduces
      health care expenditures but ultimately results in patients' reaching their
      highest level of wellness.

PMID- 9166628
TI  - Practical management of asthma.

PMID- 9166629
TI  - Allergic conjunctivitis.

PMID- 9166631
TI  - House dust allergy.

PMID- 9166630
TI  - Anaphylaxis.

PMID- 9166632
TI  - Mold allergy.

PMID- 9166633
TI  - Peak flow monitoring.

PMID- 9166634
TI  - Using an inhaler and a spacer.

PMID- 9166635
TI  - Patient with recurrent episodes of hives.

PMID- 9166636
TI  - Patient with acute onset of vesicular rash. Answers and discussion of dermatology
      case.

PMID- 9166638
TI  - Role of GABA in memory and anxiety.
AB  - This review assesses the parallel literature on the role of gamma-aminobutyric
      acid (GABA) in memory and anxiety. We review historical and new data from both
      animal and human experimentation which have helped define the key role for this
      transmitter in both these mental states. By exploring the overlap in these
      conditions in terms of pharmacology, brain circuitry, and clinical phenomenology,
      we begin to develop a theory that the two conditions are intrinsically
      interrelated. The role of GABAergic agents in dissecting out and demonstrating
      this interrelationship and in pointing the way to future research is discussed.

PMID- 9166639
TI  - Uncomplicated and comorbid obsessive-compulsive disorder in an epidemiologic
      sample.
AB  - This study investigated lifetime prevalence rates, demographic characteristics,
      childhood conduct disorder and adult antisocial features, suicide attempts, and
      cognitive impairment in individuals with obsessive-compulsive disorder (OCD)
      uncomplicated by or comorbid with any other psychiatric disorder. The data are
      from the NIMH Epidemiologic Catchment Area (ECA) study, and the current analyses
      compared subjects with uncomplicated OCD (no history of any other lifetime
      psychiatric disorder), comorbid OCD (with any other lifetime disorder), other
      lifetime psychiatric disorders, and no lifetime psychiatric disorders across
      these variables. OCD in its uncomplicated and comorbid form had significantly
      higher rates of childhood conduct symptoms, adult antisocial personality disorder
      problems, and of suicide attempts than did no or other disorders. Comorbid OCD
      subjects had higher rates of mild cognitive impairment on the Mini-Mental Status
      Exam than did subjects with other disorders. These findings suggest that a
      subgroup of OCD patients may have impulsive features, including childhood conduct
      disorder symptoms and an increased rate of suicide attempts; wider clinical
      attention to these outcomes is needed.

PMID- 9166640
TI  - Relationship between ADIS clinician's severity rating and self-report measures
      among social phobics.
AB  - Although global clinical rating scales have been a mainstay of clinical research,
      little is known about the relationship between these measures and other
      assessment modalities. The present study examined the Clinician's Severity Rating
      (CSR) from the Anxiety Disorders Interview Schedule in a sample of 186 social
      phobics. It was hypothesized that the CSR would be related to higher fear of
      negative evaluation, behavioral avoidance, social anxiety, and dysphoria, and
      that four self-report measures reflecting each of these common features of social
      phobia would contribute individually to predict clinicians' judgments of clinical
      severity using the CSR. Multiple regression analyses supported these hypotheses,
      accounting for nearly 33% of the variance in the CSR. The role of subtype of
      social phobia was also investigated. Overall, these results support the utility
      of the CSR for use with social phobics, but the relatively low proportion of
      variance accounted for raises further questions. Directions for future research
      are also discussed.

PMID- 9166641
TI  - Quality of life in social phobia.
AB  - The person's perception of his or her quality of life has been neglected in
      studies of mental health in general and anxiety disorders in particular. However,
      the judgement of the impact of a mental disorder based on symptomatic distress
      while ignoring one's overall quality of life is incomplete. In the present study,
      we examined social phobic patients' judgments of their satisfaction with various
      domains of life they deem important using the Quality of Life Inventory (QOLI;
      Frisch, unpublished). Social phobics judged their overall quality of life lower
      than Frisch's (unpublished) normative sample. Quality of life was inversely
      associated with various measures of severity of social phobia (especially social
      interaction anxiety), functional impairment, and depression. It was not, however,
      related to performance anxiety or trait anxiety. Quality of life also varied
      across combinations of subtype of social phobia and the presence/absence of
      avoidant personality disorder, and as a function of marital status. Patients
      showed significant improvement in quality of life scores after completion of
      cognitive-behavioral group therapy for social phobia.

PMID- 9166642
TI  - Preliminary investigation of the role of previous exposure to potentially
      traumatizing events in generalized anxiety disorder.
AB  - Theories of generalized anxiety disorder (GAD) highlight the relevance of
      stressful life events to this disorder's etiology. However, little empirical work
      has addressed the stressful events that may act as historical contributors to the
      development or maintenance of GAD. The present study provides an initial
      exploration of the association between exposure to potentially traumatizing
      events and GAD. In both analogue and clinical samples, GAD individuals were found
      to be more likely than nonanxious controls to report exposure to a potentially
      traumatizing event. These findings are discussed within the context of current
      theories of worry and GAD.

PMID- 9166643
TI  - Hoigne's syndrome, kindling, and panic disorder.
AB  - A review of Hoigne's syndrome (HS) is presented, and 47 cases of putative
      procaine penicillin-induced HS are discussed within the context of kindling
      models of human psychopathology. Sixty percent of the individuals with HS in our
      retrospective study reported a lifetime history of panic disorder. The risk
      factors and causal relationships among repeated injection of procaine penicillin,
      HS, and anxiety disorders, particularly panic disorder, require further
      investigation.

PMID- 9166644
TI  - Interaction of CCK-4 induced anxiety and post-cat exposure anxiety in rats.

PMID- 9166646
TI  - Raised blood albumin levels are associated with trait anxiety.

PMID- 9166645
TI  - Alteration of corticothalamic perfusion ratios during a PTSD flashback.
AB  - We performed a single photon emission computed tomography (SPECT) study of
      patients with posttraumatic stress disorder (PTSD) by measuring changes in
      regional cerebral blood flow (rCBF) during provocation by combat stimuli. A
      single patient experienced an actual flashback following exposure to combat
      sounds, exhibiting tearfulness, diaphoresis, tachypnea, and severe agitation.
      Results from his SPECT study demonstrated a dramatically altered ratio of
      cortical to subcortical perfusion during the flashback but not during the control
      scan. This altered pattern, which showed a peak of activity in the thalamus, was
      not consistent with global rCBF changes induced by hyperventilation. The
      perfusion pattern during the patient's control scan was qualitatively
      indistinguishable from any of the SPECT scans obtained for the other patients.
      This single case suggests a possible role for corticothalamic dysfunction in
      flashbacks.

PMID- 9166647
TI  - Molecular and cellular mechanisms of antidepressant drugs.
AB  - The mechanism of action of the antidepressants was reviewed through the summer of
      1995. Antagonism of monoamine transport is the primary cellular action associated
      with many antidepressant medications. However, an increased synaptic
      concentration of monoamines is not the actual mechanism of antidepressant effects
      as suggested by the time lapse between treatment initiation and the onset of
      clinical antidepressant response. Chronic administration of all antidepressants
      increases the efficiency of 5-HT transmission in the synapse, albeit by different
      mechanisms. Serotonin transporter antagonists enhance serotonergic
      neurotransmission by decreasing the functional activity of the 5-HT1A and 5-HT1B
      autoreceptors. Tricyclic antidepressants and electroconvulsive therapy enhance 5
      HT neurotransmission by increasing the responsiveness of postsynaptic 5-HT
      receptors. Monoamine oxidase inhibitors and the 5-HT1A agonists increase
      serotonergic function by desensitizing the somatodendritic autoreceptor; the
      terminal 5-HT autoreceptor is not affected by these agents. Evidence for both
      enhanced and diminished noradrenergic transmission following antidepressant
      treatment exists, although the evidence more strongly supports decreased
      noradrenergic transmission. Ongoing investigations into intracellular adaptations
      (e.g., steroid receptors, growth factors, etc.) during chronic antidepressant
      administration offer the promise of furthering our understanding of the mechanism
      of action of antidepressants.

PMID- 9166648
TI  - Comorbid depression and anxiety spectrum disorders.
AB  - The relationship between depression and anxiety disorders has long been a matter
      of controversy. The overlap of symptoms associated with these disorders makes
      diagnosis, research, and treatment particularly difficult. Recent evidence
      suggests genetic and neurobiologic similarities between depressive and anxiety
      disorders. Comorbid depression and anxiety are highly prevalent conditions.
      Patients with panic disorder, generalized anxiety disorder, social phobia, and
      other anxiety disorders are also frequently clinically depressed. Approximately
      85% of patients with depression also experience significant symptoms of anxiety.
      Similarly, comorbid depression occurs in up to 90% of patients with anxiety
      disorders. Patients with comorbid disorders do not respond as well to therapy,
      have a more protracted course of illness, and experience less positive treatment
      outcomes. One key to successful treatment of patients with mixed depressive and
      anxiety disorders is early recognition of comorbid conditions. Antidepressant
      medications, including the selective serotonin reuptake inhibitors, tricyclic
      antidepressants, and monoamine oxidase inhibitors, are highly effective in the
      management of comorbid depression and anxiety. The high rates of comorbid
      depression and anxiety argue for well-designed treatment studies in these
      populations.

PMID- 9166649
TI  - Augmentation strategies in patients with refractory depression.
AB  - In the evaluation of treatment-resistant or treatment-refractory depression
      (TRD), true resistance to antidepressant therapy must be distinguished from
      inadequate dose, duration, or compliance with past antidepressant therapy.
      Reassessment of the diagnosis may reveal psychiatric comorbidity, the presence of
      depressive subtypes, or the possibility of a medical etiology. Management of TRD
      should consider patient-specific factors; drug therapy may be directed by
      depressive subtype or the presence of psychiatric comorbidity. Increasing the
      dose or duration of current antidepressant therapy is appropriate for patients
      who have received inadequate therapy in the past. Augmentation of tricyclic
      antidepressant (TCA) or selective serotonin reuptake inhibitor (SSRI) therapy
      with thyroid hormone (T3) or lithium has been shown to be effective in open and
      controlled trials. Efficacy of other strategies such as higher-dose
      antidepressant treatment, venlafaxine therapy, combined antidepressant therapy,
      electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), or
      augmentation with pindolol or buspirone has been less well established, but
      emerging data from open studies and case reports are encouraging.

PMID- 9166650
TI  - Treatment of severe depression with the selective serotonin reuptake inhibitors.
AB  - The selective serotonin reuptake inhibitors (SSRIs) are recognized as effective
      as and better tolerated than older antidepressant therapies and have become the
      drugs of choice in the treatment of mild to moderate depression. However, there
      is a clinical impression that the SSRIs are less effective than older therapies
      in the severely depressed patient. A limited number of trials have attempted to
      address this issue. This review assesses 16 controlled studies of SSRIs in severe
      depression. The findings from a majority of studies found the SSRIs to be
      superior to placebo and as effective as but better tolerated than the tricyclic
      antidepressants (TCAs) in severely depressed patients. Although future studies
      are needed to corroborate and elaborate on these data, studies still support the
      use of SSRIs in this patient population.

PMID- 9166651
TI  - Management of the depressive component of bipolar disorder.
AB  - Acute bipolar depression (ABD) and breakthrough depression occurring during
      maintenance therapy of bipolar disorder are associated with significant morbidity
      and an increased risk of suicide. Lithium is an effective mood stabilizer for
      ABD, but its onset of antidepressant action is slow and additional antidepressant
      therapy is often prescribed. The extent to which other mood stabilizers (e.g.,
      carbamazepine and valproate) have antidepressant activity is unclear. Preliminary
      initial research suggests three potential advantages that selective serotonin
      reuptake inhibitors have over tricyclic antidepressant for ABD: possibly greater
      efficacy, fewer adverse effects, and a lower frequency of antidepressant-induced
      mania. Bupropion may also have significant advantages. However, further research
      is needed to confirm these findings. Monoamine oxidase inhibitors are the
      antidepressant of choice for atypical bipolar depression. Electroconvulsive
      therapy (ECT) has the highest response rate of all treatments for ABD. Further
      research is needed to explore combination treatments with mood stabilizers and
      antidepressants for the effective treatment of ABD.

PMID- 9166652
TI  - Depression in the medically ill: management considerations.
AB  - This article reviews the management of depression in three medical conditions
      associated with a high frequency of depression: coronary artery disease (CAD),
      cancer, and human immunodeficiency virus (HIV) infection. Major depression
      significantly increases mortality in patients with CAD. This effect of depression
      may be mediated by a decrease in heart rate variability. Tricyclic
      antidepressants (TCAs) possess Type 1A antiarrhythmic activity, which may
      increase the risk of sudden death. Initial data suggest that tricyclic
      antidepressants also may decrease heart rate variability. Antidepressant therapy
      is effective and can improve quality of life for patients with cancer or HIV
      infection. Strong social support or psychosocial interventions that improve
      coping skills may positively affect outcome in HIV infection and cancer.
      Selective serotonin reuptake inhibitors (SSRIs) and new agents may be well suited
      for use in depressed patients with medical illnesses because they lack the
      significant adverse anticholinergic and cardiovascular effects of TCAs and other
      classes of antidepressants.

PMID- 9166653
TI  - Onset of antidepressant activity: reexamining the structure of depression and
      multiple actions of drugs.
AB  - The question of when antidepressant drugs (AD) initiate significant clinical
      actions in depressed patients is still unsettled. Findings from early studies on
      whether there is a lag in the onset of therapeutic actions were in disagreement.
      More recent results with the selective serotonin reuptake inhibitors (SSRIs) and
      other new ADs indicate that clinical actions occur within the first 2 weeks. In
      this paper, evidence from efficacy studies with the ADs is reviewed and the
      methodologic and conceptual obstacles to achieving definitive results about the
      onset issue are analyzed. Depression, formerly viewed as a homogenous disorder,
      is now seen as heterogenous and multifaceted in structure. Such major structural
      components as anxiety and disturbed psychomotor functioning can be as significant
      to the core of the disorder as depressed mood itself. Further, the ADs have been
      shown to act initially on different facets of the clinical disorder which then
      result in multiple clinical actions, e.g., an initial reduction in anxiety
      followed by stimulation of motor activity. Data from the NIMH Collaborative Study
      of the Psychobiology of Depression are used to illustrate: (1) the componential
      structure of severe depressive disorder; (2) the sequence of change in the major
      behavioral components of the disorder associated with the tricyclic drugs; (3)
      the consequent "multiple" onsets of clinical actions; and (4) measurement of the
      clinical significance and visibility of the early behavioral changes. Recent
      results describing new behavioral and methodological approaches, the use of early
      clinical changes to predict outcome, and strategies for designing sound studies
      of onset are discussed.

PMID- 9166654
TI  - Depression and axis II disorders: comorbidity and relationship to
      cooperativeness.
AB  - The diagnosis of depression and Axis II personality disorders have been found to
      co-occur in people, and the purpose of this paper is to examine the relationships
      between chronicity of depression and Axis II diagnosis. We assessed for the
      prevalence of two Axis II disorders, Antisocial Personality Disorder (APD) and
      Borderline Personality Disorder (BPD). Patients who were evaluated in a tertiary
      care center were diagnosed as having Chronic Major Depressive Disorder (CMDD),
      Dysthymic disorder (DD), or Acute Major Depressive Disorder (AMDD). We expected
      the prevalence of Axis II disorders to increase with increasing depression
      chronicity. Cloninger et al. (1993, Arch Gen Psychiatry 50:975-988; 1994) have
      proposed that temperament and character factors may be predictors of personality
      disorders. The instrument originally developed to measure these factors was the
      Tri-dimensional Personality Questionnaire (TPQ), which was later revised to
      produce the Temperament and Character Inventory (TCI). There is evidence that TCI
      scores help predict the presence of Axis II disorders. We hypothesized that one
      component of the TCI, cooperativeness, would be lower in CMDD than DD or AMDD,
      reflecting a relationship between Axis II disorders and chronicity of depression.
      From our sample, no patients had APD and there was not a significant difference
      between the number of patients with BPD in each of the depression groups.
      Furthermore, there was not a significant difference between cooperativeness
      scores among each of the groups. The implications of these findings are
      discussed.

PMID- 9166655
TI  - Barriers to seeking treatment for major depression.
AB  - The purpose of this study was to examine the reasons people with an episode of
      Major Depression do or do not seek treatment for the episode. We interviewed 101
      persons who met criteria for an RDC Major Depressive episode that lasted at least
      4 weeks within 3 years of the interview date, exploring in detail the reasons
      they gave for seeking or not seeking treatment. GAS ratings indicated that all
      subjects were moderately impaired at the time of the episode. We found that 55%
      of the subjects did not seek treatment for this episode, while 45% did.
      Significant predictors of treatment seeking included a history of prior
      treatment, higher education, and greater episode length. Non-seekers felt they
      could handle the episode themselves, did not consider it serious or did not
      recognize it as an illness. Seekers on the other hand felt the episode was too
      painful and lasted too long and caused significant disruption in their
      interpersonal relationships and role functioning. We discuss the implications of
      these findings in terms of the importance of continued educational efforts to
      encourage treatment seeking as well as the need for further research to explore
      the manner in which people decide that affective signs and symptoms have reached
      a threshold that leads to treatment seeking.

PMID- 9166656
TI  - Effects of artificial rearing on electrophysiology and behavior in adult rats.
AB  - Maternal separation during crucial periods of development can lead to both
      physiological and behavioral sequelae. However, the exact consequences of
      maternal separation are paradigm dependent. The present study utilized complete
      artificial rearing (AR) to evaluate the effects of maternal separation on
      behavioral and electrophysiological functioning. In this procedure
      thermoregulation and weight gain progress are normal, but pups are deprived of
      any maternal influence from postnatal day 4 to 12. Artificial rearing was found
      to have no effect on EEG as assessed using spectral analyses. However, the N1
      component of the auditory event-related potential (ERP) in artificially reared
      rats was significantly delayed. Artificial rearing had no effect on overall
      locomotor activity, but artificially reared rats were more behaviorally inhibited
      than suckled controls in the open field. This study suggests that artificial
      rearing or chronic maternal separation (24 h/day from PN4 to PN12), while not
      producing gross behavioral effects, can produce selective enduring alterations in
      neurosensory responses.

PMID- 9166657
TI  - Decision model for the acute treatment of mania.
AB  - Decision making in psychiatric diagnosis and treatment has not been evaluated
      systematically. The authors present a model for treatment of an acute manic
      episode using a decision analysis software program. Six treatment options were
      put into the model: lithium, valproate, carbamezepine, electroconvulsive therapy,
      clonazepam, and neuroleptics. Each treatment was evaluated on three factors,
      efficacy, tolerability, and cost, using data from the literature and pharmacy and
      billing information. Output from the computer program identified three top
      choices among the six options: valproate, carbamazepine, and lithium, with
      valproate emerging as the first choice using the data we inputted.

PMID- 9166658
TI  - Course of psychomotor agitation during pharmacotherapy of depression: analysis
      from double-blind controlled trials with fluoxetine.
AB  - Psychomotor agitation, a common clinical feature of major depression, may first
      emerge or intensify during pharmacotherapy. Whether agitation is part of the
      underlying course of depression or iatrogenic complicates treatment planning. We
      analyzed data from blinded clinical trials involving 4,737 patients with major
      depression assigned to a selective serotonin reuptake inhibitor (fluoxetine), a
      comparator antidepressant (usually a tricyclic antidepressant [TCA]), or placebo.
      Item 9 of the Hamilton Depression Rating Scale was used to assess the degree of
      psychomotor agitation. The vast majority of depressed patients exhibited baseline
      psychomotor agitation. The rate of increased agitation from baseline during acute
      pharmacotherapy was comparable between fluoxetine and either placebo or TCAs.
      Substantial emergence of psychomotor agitation also occurred at a similar
      incidence across the three treatment groups and typically appeared within the
      first 3 wk. Improvement in agitation was significantly more prominent (P < 0.001)
      among fluoxetine-treated than among placebo-treated patients. Fluoxetine-treated
      patients demonstrated numerically superior improvement rates compared with TCA
      treated patients; however, this difference was not significant. Data derived from
      this large series of clinical trials suggested no evidence that either fluoxetine
      or TCAs induced psychomotor agitation at rates exceeding the natural course of
      the disorder over time (placebo cohort). On the contrary, pharmacotherapy with
      either fluoxetine or TCAs was typically associated with diminished agitation,
      probably as part of the response pattern of depression.

PMID- 9166659
TI  - Effect of continuation treatment on residual symptoms in late-life depression:
      how well is "well"?
AB  - The objectives of this report were (1) to describe residual depressive symptoms
      in elderly patients during continuation therapy with combined nortriptyline and
      interpersonal psychotherapy; (2) to determine which symptoms were persistent; (3)
      to determine the clinical correlates of residual depressive symptoms; and (4) to
      document distinct response pattern clusters during combined continuation therapy.
      METHOD: Box plot analyses of Hamilton depression scores and Global Assessment
      Scale scores, repeated twice monthly over 4 months, were conducted using data
      from 105 elderly depressives. Temporal trends in the data were examined via
      random regression analysis. Individual trajectories for each of the 105 patients
      were examined for patterns of response during continuation therapy. RESULTS: We
      observed a low mean Hamilton rating of 7 (SD = 2.3) at the start of continuation
      therapy and 5 (SD = 3.0) at the end. Both Hamilton and GAS scores showed modest
      but significant improvement over time. Hamilton variability was most apparent in
      symptoms of mood lowering, apathy, anxiety (psychological and somatic), feelings
      of guilt, anergia, insomnia, and loss of libido; other symptoms (retardation,
      agitation, hypochondriasis, loss of appetite, loss of weight, suicidal ideation,
      and loss of insight) showed clear resolution. A diagnosis of RDC situational
      depression was associated with higher levels of residual symptoms, while level of
      chronic medical burden, personality dysfunction, and social support were not.
      Examination of response patterns showed that a quarter of patients experienced
      one or more brief symptomatic exacerbations. CONCLUSION: On average, an excellent
      level of symptom resolution was achieved for most patients with Hamilton scores
      comparable to those seen in healthy elderly controls. These data support a
      position of therapeutic optimism in late-life depression and underscore full
      remission as an achievable therapeutic goal.

PMID- 9166660
TI  - Managing rapid metabolizers of antidepressants.
AB  - Depressed patients who rapidly metabolize antidepressants may be common, and may
      not respond to even high doses of antidepressants if subtherapeutic plasma levels
      are produced. Rapid metabolizers (RMs) are identifiable if patients are on
      tricyclic antidepressants (TCAs), and TCA plasma levels (commonly available) are
      monitored. Strategies to achieve therapeutic levels in RMs include: (1)
      megaprescribing, or (2) inhibiting the metabolism of the parent drug.
      Megaprescribing TCAs runs the risk of markedly elevating levels of potentially
      toxic hydroxy metabolites. In this study twelve depressed, non-responding RMs
      were identified while taking the TCA, desipramine. Fluoxetine or paroxetine,
      selective serotonin re-uptake inhibitors (SSRIs) known to potently inhibit
      cytochrome P450 2D6 (the isoenzyme responsible for desipramine metabolism), was
      then added to continuing desipramine. Therapeutic range desipramine levels were
      achieved in ten patients, and seven of the ten achieved excellent or good
      sustained responses. The combination SSRI and TCA therapy was well tolerated.
      Whether response primarily reflected the TCA at therapeutic range levels, or a
      synergistic serotonin-noradrenaline interaction between the respective
      antidepressants, requires further clarification. The results of this open study
      suggest the need for controlled trials of antidepressant metabolism inhibition in
      RMs.

PMID- 9166661
TI  - Impact of natural IRS-1 mutations on insulin signals: mutations of IRS-1 in the
      PTB domain and near SH2 protein binding sites result in impaired function at
      different steps of IRS-1 signaling.
AB  - Insulin receptor substrate-1 (IRS-1) is one of the major substrates of insulin
      receptor tyrosine kinase and mediates various insulin signals downstream. In this
      study, we have examined the impact of three natural IRS-1 mutations identified in
      NIDDM patients (G971R, P170R, and M209T) on insulin signaling. G971R is located
      near src homology 2 protein binding sites, and P170R and M209T are located in the
      phosphotyrosine binding domain of IRS-1. 32D-IR cells, stably overexpressing
      human insulin receptor, were transfected with wild-type human IRS-1 cDNA (WT) or
      three mutant IRS-1 cDNAs and analyzed. All the cell lines expressing mutant IRS-1
      showed a significant reduction in [3H]thymidine incorporation compared with WT.
      Upon insulin stimulation, cells expressing G971R showed a 39% decrease (P <
      0.005) in phosphatidylinositol 3-kinase (PI 3-kinase) activity, a 43% decrease (P
      < 0.01) in binding of the 85-kDa regulatory subunit of PI 3-kinase, and a 22%
      decrease (P < 0.05) in mitogen-activated protein kinase activity compared with
      those expressing WT. Cells expressing P170R and M209T showed slight but
      significant decreases in PI 3-kinase activity (17 and 14%, respectively; both P <
      0.05) and in binding of p85 (22 and 16%, respectively; both P < 0.05) and a
      greater decrease in mitogen-activated protein kinase activity (41 and 43%,
      respectively; both P < 0.005) compared with WT. After insulin stimulation, cells
      expressing P170R and M209T showed significant decreases in IRS-1 phosphorylation
      (37 and 42%, respectively; both P < 0.05) and in IRS-1 binding to the insulin
      receptor (48 and 53%, respectively; P < 0.01) compared with WT. G971R showed no
      changes in IRS-1 phosphorylation and in IRS-1 binding to the insulin receptor
      compared with WT. These data suggest that the impaired mitogenic response of
      P170R and M209T was mainly due to reduced binding to the insulin receptor,
      whereas the impaired response of G971R was mainly due to reduced association with
      PI 3-kinase p85.

PMID- 9166662
TI  - Treatment with neutralizing antibodies specific for IL-1beta prevents
      cyclophosphamide-induced diabetes in nonobese diabetic mice.
AB  - Interleukin-1 (IL-1) has been shown to be involved in the pathogenesis of IDDM,
      but it is not clear which form, IL-1alpha or IL-1beta, is predominantly
      implicated. In this study, we have evaluated the contribution of IL-1beta by
      treating diabetes-prone nonobese diabetic (NOD) mice with specific neutralizing
      antibodies. First, we assessed the neutralizing potential of these antibodies in
      C57BL/6 mice under acute septic shock by measuring IL-1beta in sera 4 h after
      lipopolysaccharide injection. One milligram and 0.1 mg of anti-IL-1beta
      antibodies (Abs) were capable of neutralizing the IL-1beta produced, and the
      effect persisted for at least 5 days. Second, we evaluated the role of IL-1beta
      in the cyclophosphamide (CY)-accelerated model of diabetes. Nondiabetic male NOD
      mice were injected with 200 mg/kg CY and treated twice weekly with anti-IL-1beta
      Ab. The incidence of diabetes reached 76 and 100% in the control groups treated
      with 0.25 and 0.1 mg rabbit IgG, respectively. In contrast, only 34% of mice
      treated with 0.25 mg of anti-IL-1beta Ab became diabetic. In the group treated
      with 0.1 mg of anti-IL-1beta Ab, 89% of the mice became diabetic in the same
      period of time, demonstrating that the protective effect was dose dependent. Our
      results show that IL-1beta is a critical effector molecule in this model of IDDM
      and that its specific inhibition could be an attractive target for therapeutic
      intervention.

PMID- 9166663
TI  - B-cells are required for the initiation of insulitis and sialitis in nonobese
      diabetic mice.
AB  - Nonobese diabetic (NOD) mice spontaneously develop an acute onset of
      hyperglycemia reminiscent of human type I diabetes. The disease is the end result
      of a mononuclear cell infiltration of pancreatic islets (insulitis), culminating
      in the selective destruction of islet beta-cells by autoreactive T-cells. NOD
      mice also exhibit defects in B-cell tolerance as manifested by the presence of
      autoantibodies against islet cell autoantigens. Based on the potential ability of
      B-cells to act as antigen presenting cells, we hypothesized that autoreactive B
      cells of NOD mice may be necessary for the activation of islet reactive CD4+ T
      cells. In the present study, we utilized an anti-mu antibody to induce in vivo
      depletion of B-cells and found that B-cell depletion completely abrogates the
      development of insulitis and sialitis in NOD mice. In contrast, control IgG
      treated NOD mice developed insulitis and sialitis by 5 weeks of age.
      Additionally, the discontinuation of anti-mu chain antibody treatment led to the
      full restoration of the B-cell pool and the reappearance of insulitis and
      sialitis. Thus, we conclude that B-cells are a requisite cell population for the
      genesis of the inflammatory lesions of the islets of Langerhans. This finding
      suggests that autoreactive B-cells may act as the antigen presenting cells
      necessary for the initial activation of beta-cell-reactive CD4+ T-cells
      implicated in the pathogenesis of autoimmune diabetes.

PMID- 9166664
TI  - Islet capillary blood pressure increase mediated by hyperglycemia in NIDDM GK
      rats.
AB  - This study was performed to measure pancreatic islet capillary pressure under
      basal conditions and after an acute glucose stimulation of insulin release in
      normal rats. In addition, the islet capillary pressure was estimated in GK rats,
      an animal model of NIDDM. Hydrostatic pressure in single pancreatic islet
      capillaries was determined in vivo by direct measurement using the micropuncture
      technique. The pancreatic islets were visualized by injection of neutral red.
      This intravital staining had no effect on islet function, whole pancreatic and
      islet blood flow, and capillary blood pressure in the exocrine pancreas. Islet
      capillary blood pressure in normoglycemic Wistar F rats was estimated at 3.1 +/-
      0.3 mmHg (n = 15). Administration of D-glucose (1 g/kg) doubled this value,
      whereas no effect was seen after injection of an equimolar dose of the non
      metabolizable glucose-derivative 3-O-methyl glucose. In GK rats, basal islet
      capillary blood pressure was increased (5.7 +/- 0.4 mmHg; n = 10; P < 0.001) when
      compared with the control Wistar F rats. Reduction of blood glucose levels in GK
      rats with phlorizin treatment showed this increased basal islet capillary
      pressure in GK rats to be glucose dependent and reversible. In the present study,
      we have for the first time shown that both acute and chronic hyperglycemia
      augment islet capillary pressure. The effects of a chronically increased islet
      capillary pressure on long-term islet function remain to be determined.

PMID- 9166665
TI  - Characterization of the unusual insulin of Psammomys obesus, a rodent with
      nutrition-induced NIDDM-like syndrome.
AB  - Psammomys obesus fed a high-calorie diet develops a NIDDM-like syndrome. The use
      of reverse-phase high-performance liquid chromatography (HPLC) to study Psammomys
      insulin biosynthesis and release revealed a very delayed elution time for the
      Psammomys insulin peak appearing near the position of human proinsulin. This
      unusual peak was initially thought to represent partially processed insulin on
      the basis of its molecular size and susceptibility to trimming by
      carboxypeptidase B (CpB). However, the findings of an active carboxypeptidase E
      (CpE) enzyme and the normal amidated forms of gastrin and cholecystokinin
      octapeptide (CCK-8) in Psammomys tissues were inconsistent with CpE-related
      aberrant processing of insulin. Moreover, amino acid sequencing of the delayed
      peak of Psammomys insulin revealed fully processed insulin with amino acid
      sequence as predicted by the cDNA. The unique presence of a B-30 phenylalanine
      residue, resulting in an increased hydrophobicity of the insulin molecule,
      probably underlies the marked delay in elution time on HPLC. The unusual
      structure of Psammomys insulin does not appear to contribute to the
      proinsulinemia observed in diabetic Psammomys since the HPLC-purified molecule
      did not inhibit PC1 and PC2 convertase activities in an in vitro assay.

PMID- 9166667
TI  - Regulation of insulin secretion from novel engineered insulinoma cell lines.
AB  - In the accompanying article, we describe the creation of novel cell lines derived
      from RIN 1046-38 rat insulinoma cells by stable transfection with combinations of
      genes encoding human insulin, GLUT2, and glucokinase. Herein we describe the
      regulation of insulin secretion and glucose metabolism in these new cell lines. A
      cell line (betaG I/17) expressing only the human proinsulin transgene exhibits a
      clear increase in basal insulin production (measured in the absence of
      secretagogues) relative to parental RIN 1046-38 cells. betaG I/17 cells
      engineered for high levels of GLUT2 expression and a twofold increase in
      glucokinase activity (betaG 49/206) or engineered for a 10-fold increase in
      glucokinase activity alone (betaG 40/110) exhibit a 66% and 80% suppression in
      basal insulin secretion relative to betaG I/17 cells, respectively. As a result,
      betaG 49/206 and betaG 40/110 cells exhibit potent insulin-secretory responses to
      glucose alone (6.1- and 7.6-fold, respectively) or to glucose plus
      isobutylmethylxanthine (10.8- and 15.1-fold, respectively) that are clearly
      larger than the corresponding responses of betaG I/17 or parental RIN 1046-38
      cells. betaG 49/206 and betaG 40/110 cells also exhibit a rapid and sustained
      response to glucose plus isobutyl-methylxanthine in perifusion studies that is
      clearly larger in magnitude than that of the two control lines. Glucose dose
      response studies show that both engineered and non-engineered lines respond
      maximally to submillimolar concentrations of glucose and that betaG 49/206 cells
      are the most sensitive to low concentrations of the hexose, consistent with their
      clearly elevated rate of [5-3H]glucose usage. Finally, 5-thioglucose, a potent
      inhibitor of low-K(m) hexokinases, most effectively normalizes glucose
      concentration dependence for insulin secretion in the cell line with highest
      glucokinase expression (betaG 40/110). We conclude that GLUT2 and/or glucokinase
      expression imposes tight regulation of basal insulin secretion in cell lines that
      overexpress human proinsulin, allowing a marked improvement in the range of
      secretagogue responsiveness in such cells.

PMID- 9166666
TI  - Novel insulinoma cell lines produced by iterative engineering of GLUT2,
      glucokinase, and human insulin expression.
AB  - Cellular engineering studies in our group are directed at creating insulin
      secreting cell lines that simulate the performance of the normal islet beta-cell.
      The strategy described in this article involves the stepwise stable introduction
      of genes relevant to beta-cell performance into the RIN 1046-38 insulinoma cell
      line, a process that we term "iterative engineering." RIN cells stably engineered
      to contain multiple copies of the human insulin gene exhibit a large increase in
      insulin content, such that they approach the content of human islets assayed in
      parallel. Analysis by high-performance liquid chromatography demonstrates that
      these engineered cell lines process human proinsulin to mature insulin with high
      efficiency. Cell lines that are further engineered to express the GLUT2 and
      glucokinase genes demonstrate stable expression of the three transgenes for the
      full lifetime of the lines produced to date (6 months to 1 year in continuous
      culture). Transplantation of the engineered cell lines into nude rats reveals
      that stably integrated genes are expressed at constant levels in the in vivo
      environment over the full duration of experiments performed (48 days). Several
      endogenous genes expressed in normal beta-cells, including rat insulin, amylin,
      sulfonylurea receptor, and glucokinase, are stably expressed in the insulinoma
      lines during these in vivo studies. Endogenous GLUT2 expression, in contrast, is
      rapidly extinguished during in vivo passage. The loss of GLUT2 is overcome in
      engineered cell ines in which transporter expression is provided by a stably
      transfected transgene. These results suggest that a potential advantage of the
      iterative engineering approach may be to preserve stability of function and
      phenotype, particularly in the in vivo setting.

PMID- 9166668
TI  - Proinsulin conversion in GH3 cells after coexpression of human proinsulin with
      the endoproteases PC2 and/or PC3.
AB  - Proinsulin conversion to insulin occurs in secretory granules of pancreatic beta
      cells. This processing has been suggested to require both the endoproteases PC2
      and PC3 with each cleaving at only one of the two sites linking the insulin A-
      and B-chains with C-peptide. To evaluate this in an appropriate cellular setting,
      conversion of human proinsulin was followed in GH3 (rat pituitary) cells normally
      unable to convert this prohormone but equipped with the regulated secretory
      pathway. For this purpose, human proinsulin was expressed in GH3 cells, alone or
      in combination with PC2 and/or PC3, using recombinant adenoviruses. Cells were
      infected with the given adenoviruses and 24 h later were pulse-chased. Kinetics
      of proinsulin conversion were monitored by reverse-phase high-performance liquid
      chromatography. It was observed that while the two endoproteases do display a
      preference for a single site of cleavage (PC2 at the A-chain/C-peptide junction;
      PC3 at the B-chain/C-peptide junction) and act in a synergistic manner to promote
      proinsulin conversion, either PC2 or PC3 alone can cleave at both sites to fully
      convert proinsulin to insulin. These results also show that a cell can be
      successfully infected by three different recombinant adenoviruses.

PMID- 9166669
TI  - Skeletal muscle triglyceride levels are inversely related to insulin action.
AB  - In animal studies, increased amounts of triglyceride associated with skeletal
      muscle (mTG) correlate with reduced skeletal muscle and whole body insulin
      action. The aim of this study was to test this relationship in humans. Subjects
      were 38 nondiabetic male Pima Indians (mean age 28 +/- 1 years). Insulin
      sensitivity at physiological (M) and supraphysiological (MZ) insulin levels was
      assessed by the euglycemic clamp. Lipid and carbohydrate oxidation were
      determined by indirect calorimetry before and during insulin administration. mTG
      was determined in vastus lateralis muscles obtained by percutaneous biopsy.
      Percentage of body fat (mean 29 +/- 1%, range 14-44%) was measured by underwater
      weighing. In simple regressions, negative relationships were found between mTG
      (mean 5.4 +/- 0.3 micromol/g, range 1.3-1.9 micromol/g) and log10M (r = -0.53, P
      < or = 0.001), MZ (r = -0.44, P = 0.006), and nonoxidative glucose disposal (r = 
      0.48 and -0.47 at physiological and supraphysiological insulin levels,
      respectively, both P = 0.005) but not glucose or lipid oxidation. mTG was not
      related to any measure of adiposity. In multiple regressions, measures of insulin
      resistance (log10M, MZ, log10[fasting insulin]) were significantly related to mTG
      independent of all measures of obesity (percentage of body fat, BMI, waist-to
      thigh ratio). In turn, all measures of obesity were related to the insulin
      resistance measures independent of mTG. The obesity measures and mTG accounted
      for similar proportions of the variance in insulin resistance in these
      relationships. The results suggest that in this human population, as in animal
      models, skeletal muscle insulin sensitivity is strongly influenced by local
      supplies of triglycerides, as well as by remote depots and circulating lipids.
      The mechanism(s) underlying the relationship between mTG and insulin action on
      skeletal muscle glycogen synthesis may be central to an understanding of insulin
      resistance.

PMID- 9166670
TI  - Circulating leptin in normal children and during the dynamic phase of juvenile
      obesity: relation to body fatness, energy metabolism, caloric intake, and sexual
      dimorphism.
AB  - In 112 obese compared with 42 lean children, we found that serum leptin is
      elevated early in the evolution of childhood-onset obesity (28.4 +/- 1.4 vs. 4.5
      +/- 0.4 ng/ml in lean children, P < 0.0001) and correlates with adiposity. Obese
      children also had higher serum leptin normalized to fat mass. Despite high serum
      leptin, obese children ingested 2-3 times more calories than did lean control
      subjects (P < 0.0001) and gained weight rapidly (10.2 +/- 0.3 vs. 2.9 +/- 0.1
      kg/year in control subjects, P < 0.0001). Girls had higher leptin levels than did
      boys, in obese as well as in nonobese children, and showed a closer correlation
      between adiposity and serum leptin. Elevation of serum leptin was comparable
      before and after puberty in obese boys, but puberty further increased leptin
      levels in obese girls (36 +/- 3 ng/ml), resulting in a clear sexual dimorphism
      with pubertal obese boys (22 +/- 5 ng/ml, P < 0.005). In conclusion, increased
      serum leptin reflects but does not halt fat deposition in childhood obesity.
      After normalization to body adiposity, leptin was found to be increased
      independently by obesity status, female sex, and female sexual maturation.

PMID- 9166671
TI  - Mechanisms of the kinetic defect in insulin action in obesity and NIDDM.
AB  - To evaluate kinetic defects in insulin action, we performed time-course studies
      during hyperinsulinemic (120 mU x m(-2) x min(-1)) isoglycemic clamps in seven
      subjects with NIDDM (194 +/- 29 mg/dl) and in seven lean and seven obese
      nondiabetic subjects. The time course of whole-body glucose disposal rate (GDR),
      leg glucose uptake (LGU), hepatic glucose output (HGO), and muscle insulin
      receptor tyrosine kinase (IRTK) activation were measured. The obese and NIDDM
      subjects had marked delays in activation of GDR (T50 74 +/- 14 and 95 +/- 15 min,
      respectively, compared with 33 +/- 2 min in lean control subjects), arteriovenous
      glucose difference (T50 80 +/- 12 and 109 +/- 31 min compared with 30 +/- 3 min)
      and LGU (T50 89 +/- 25 and 98 +/- 27 min compared with 29 +/- 4 min). All three
      measurements reached normal levels in the NIDDM group after 4-5 h of insulin
      infusion. Although only a limited number of data points could be obtained from
      serial muscle biopsies, no delay in the rate of activation of IRTK was apparent
      in the obese and NIDDM groups. In conclusion, 1) in obese and NIDDM subjects,
      insulin-mediated GDR and LGU are delayed to a similar degree; 2) mass action
      normalizes GDR and LGU in NIDDM, but only after several hours of insulin
      infusion; and 3) The kinetic defect in NIDDM and obesity most likely involves
      intracellular loci distal to activation of the insulin receptor kinase.

PMID- 9166672
TI  - Metabolic defects in lean nondiabetic offspring of NIDDM parents: a cross
      sectional study.
AB  - First-degree relatives of NIDDM patients have an approximately 40% lifetime risk
      of developing diabetes, and insulin resistance is the best predictor. However,
      insulin resistance is altered by many other factors, including age, diet,
      exercise, and medications. To investigate the metabolic and endocrine alterations
      associated with insulin resistance when all the above confounding factors are
      excluded, we examined the first phase of insulin secretion and insulin
      sensitivity in 49 white normoglycemic (4.99 +/- 0.51 vs. 4.95 +/- 0.41 mmol/l)
      nonexercising lean (BMI, 24 +/- 3 vs. 23 +/- 2 kg/m2; 105 +/- 3 vs. 104 +/- 3% of
      ideal body weight) offspring of NIDDM patients. These subjects were compared with
      29 matched healthy control subjects by means of an intravenous glucose bolus (0.3
      g/kg body wt), immediately followed by a euglycemic-hyperinsulinemic
      (approximately 420 pmol/l) clamp, along with lipid and amino acid profiles. The
      offspring showed fasting hyperinsulinemia (40.6 +/- 15.8 vs. 30.9 +/- 13.6
      pmol/l; P = 0.005) and higher free fatty acid (FFA) levels (582 +/- 189 vs. 470
      +/- 140 micromol; P = 0.007), whereas triglycerides, total cholesterol, and HDL
      and LDL cholesterol levels were comparable with those of control subjects.
      Alanine (320 +/- 70 vs. 361 +/- 73 micromol/l; P = 0.017), serine (P = 0.05), and
      glutamine and glycine (P = 0.02) were lower in the offspring than in the control
      subjects, whereas branched-chain amino acids (343 +/- 54 vs. 357 +/- 54
      micromol/l; P = 0.28) were not different. Insulin sensitivity was lower (4.86 +/-
      1.65 vs. 6.17 +/ 1.56 mg x kg(-1) x min(-1); P = 0.001), and an inverse
      correlation with fasting FFAs in the offspring (adjusted R2 = 0.21, P = 0.0005),
      but not in control subjects (adjusted R2 = 0.03, P = 0.368), was found. Because
      insulin sensitivity in the offspring appeared to be a mixture of three
      distributions, they were subdivided into three subgroups: very low, low, and
      normal insulin sensitivity (20, 47, and 33%, respectively). The same alterations
      in amino acid and FFA metabolism were observed in the very low and low subgroups
      but not in the normal subgroup. The first phase of insulin secretion appeared to
      compensate significantly for insulin resistance in the low subgroup versus the
      normal subgroup and controls, but was inappropriately low in the subgroup with
      very low insulin sensitivity considering its degree of insulin resistance. In
      conclusion, lean insulin-resistant offspring of NIDDM parents showed 1) trimodal
      distribution of insulin sensitivity, 2) high fasting plasma FFA concentrations,
      3) an inverse correlation between insulin sensitivity and FFA concentration, 4)
      low plasma gluconeogenic amino acid concentrations, and 5) defective insulin
      secretion when related to insulin sensitivity in the subgroup of very resistant
      offspring. These results suggest that, in this white population, insulin
      sensitivity may be determined by a single major gene and that alterations in FFA
      metabolism may play a role in the pathogenesis of NIDDM.

PMID- 9166673
TI  - Evidence of increased systemic glucose production and gluconeogenesis in an early
      stage of NIDDM.
AB  - To assess the mechanisms of fasting hyperglycemia in NIDDM patients with mild
      elevation of fasting plasma glucose (FPG) compared with NIDDM patients with overt
      hyperglycemia, we studied 29 patients with NIDDM, who were divided in two groups
      according to their fasting plasma glucose (<7.8 and > or =7.8 mmol/l for groups A
      and B, respectively), and 16 control subjects who were matched with NIDDM
      patients for age, sex, and body mass index. All subjects were infused with [3
      3H]glucose between 10:00 P.M. and 10:00 A.M. during overnight fasting to
      determine glucose fluxes. In 27 subjects (17 diabetic and 10 control), [U
      14C]alanine was simultaneously infused between 4:00 A.M. and 10:00 A.M. to
      measure gluconeogenesis (GNG) from alanine. Arterialized-venous plasma samples
      were collected every 30 min for measurement of glucose fluxes, GNG, and
      glucoregulatory hormones. In group A, plasma glucose, rate of systemic glucose
      production (SGP), and GNG were greater than in control subjects (7.2 +/- 0.2 vs.
      4.9 +/- 0.1 mmol/l, 10.9 +/- 0.2 vs. 9.5 +/- 0.3 micromol x kg(-1) x min(-1), and
      0.58 +/- 0.04 vs. 0.37 +/- 0.02 micromol x kg(-1) x min(-1), respectively, for
      group A and control subjects; mean value 8:00 A.M.-10:00 A.M., all P < 0.05).
      Both increased SGP and GNG correlated with plasma glucose in all subjects (r =
      0.77 and r = 0.75, respectively, P < 0.005). Plasma counterregulatory hormones
      did not differ in NIDDM patients compared to control subjects. The present
      studies demonstrate that SGP and GNG are increased in NIDDM patients without
      overt fasting hyperglycemia. Thus these metabolic abnormalities primarily
      contribute to early development of overnight and fasting hyperglycemia in NIDDM.

PMID- 9166674
TI  - Regulation of glycogen synthase activity in cultured skeletal muscle cells from
      subjects with type II diabetes: role of chronic hyperinsulinemia and
      hyperglycemia.
AB  - Human skeletal muscle cultures (HSMCs) from type II diabetic subjects were used
      to determine whether metabolic abnormalities such as hyperglycemia or
      hyperinsulinemia contribute to the defective muscle glycogen synthase (GS)
      activity present in this disorder. Following approximately 6 weeks of growth,
      diabetic cultures were fused for 4 days in normal, hyperglycemia, or
      hyperinsulinemia medium. Fusion of diabetic HSMCs in hyperglycemia medium (20
      mmol/l vs. 5.5 mmol/l) had no effect on GS fractional velocity (FV) or mRNA
      levels, but impaired acute insulin-stimulation of glycogen synthesis and GS
      activity at 0.1 mmol/l glucose-6-phosphate, and reduced GS protein content by
      approximately 15% (P < 0.05). Fusion of diabetic muscle cultures in
      hyperinsulinemia medium (30 micromol/l vs. 22 pmol/l) improved basal GS activity,
      increasing the reduced GS FV by approximately 50% (P < 0.05), and decreasing the
      elevated Km(0.1) (half-maximal substrate concentration) by approximately 47% (P <
      0.05). Hyperinsulinemia also significantly increased (P < 0.05) the reduced GS
      mRNA and protein levels of diabetic muscle to levels similar to that in
      nondiabetic subjects. In contrast to the improvements in the basal state,
      hyperinsulinemia completely abolished acute insulin responsiveness of GS activity
      and glycogen synthesis in muscle of type II diabetic subjects. The combination of
      hyperinsulinemia and hyperglycemia produced effects on both basal and insulin
      responsive GS FV and mRNA similar to hyperinsulinemia alone, but hyperinsulinemia
      prevented hyperglycemia's effect of lowering GS protein and glycogen synthesis.
      We concluded that, in diabetic muscle, hyperinsulinemia may serve to partially
      compensate for the impaired basal GS activity and for the adverse effects of
      hyperglycemia on GS protein content, activity, and glycogen formation by both pre
      and posttranslational mechanisms. Despite these beneficial effects,
      hyperinsulinemia also induces severe impairment of insulin-stimulated GS activity
      and glycogen formation, which may contribute to acquired muscle insulin
      resistance of type II diabetes.

PMID- 9166675
TI  - Acute postchallenge hyperinsulinemia predicts weight gain: a prospective study.
AB  - The relationships of insulin secretion and insulin action to body weight are
      incompletely understood. Obesity is associated with reduced sensitivity to
      insulin and high fasting and postprandial serum insulin levels. However, it is
      unknown whether insulin secretion rises to compensate for insulin resistance or
      high insulin secretion promotes body weight gain and the development of insulin
      resistance. To shed light on this question, we examined weight gain over an
      interval of 16.7 +/- 3.9 years (mean +/- SD) in 107 glucose-tolerant offspring
      (48 men, 59 women) of two parents with NIDDM. The offspring had a baseline
      intravenous glucose tolerance test, at which time they were aged 32.9 +/- 9.7
      years, and only those who did not develop diabetes during the follow-up period
      were included. We estimated insulin sensitivity with the insulin sensitivity
      index from Bergman's minimal model of glucose disposal and acute insulin
      secretion from the incremental area under the insulin curve in the first 10 min
      of the intravenous glucose tolerance test. Weight-gain rate (g/year) was defined
      as the regression slope of each subject's body weight over time. High acute
      insulin secretion, young age, and low baseline percent ideal body weight (IBW)
      were each associated with a high rate of weight gain. After adjustment for
      differences in age and IBW, statistically significant effects of insulin
      sensitivity (P = 0.05) as well as acute insulin secretion (P = 0.001) were
      obtained. To estimate the effects of acute insulin secretion and insulin
      sensitivity on the average rate of weight gain (adjusting for age and IBW), the
      study group was stratified into four subgroups by dividing it at the medians of
      these two variables. Among those with low acute insulin secretion, weight-gain
      rate was the same regardless of whether insulin sensitivity was low or high (176
      and 152 g/year, respectively). Among those with high acute insulin secretion,
      mean weight-gain rate was still rather low in those with low insulin sensitivity
      (271 g/year), but it was quite high in those with high insulin sensitivity (672
      g/year; significantly higher than in all other subgroups). Therefore a high first
      phase insulin response to intravenous glucose is a risk factor for long-term
      weight gain, and this effect is particularly manifested in insulin-sensitive
      individuals.

PMID- 9166676
TI  - D-glucose stimulates mesangial cell GLUT1 expression and basal and IGF-I
      sensitive glucose uptake in rat mesangial cells: implications for diabetic
      nephropathy.
AB  - The complications of diabetes arise in part from abnormally high cellular glucose
      uptake and metabolism. To determine whether altered glucose transporter
      expression may be involved in the pathogenesis of diabetic nephropathy, we
      investigated the effects of elevated extracellular glucose concentrations on
      facilitative glucose transporter (GLUT) expression in rat mesangial cells. GLUT1
      was the only transporter isoform detected. Cells exposed to 20 mmol/l glucose
      medium for 3 days demonstrated increases in GLUT1 mRNA (134%, P < 0.002), GLUT1
      protein (68%, P < 0.02), and V(max) (50%, P < 0.05) for uptake of the glucose
      analog [3H]2-deoxyglucose (3H2-DOG), when compared to cells chronically adapted
      to physiologic glucose concentrations (8 mmol/l). The increase in GLUT1 protein
      was sustained at 3 months, the latest time point tested (77% above control, P <
      0.01). In contrast, hypertonic mannitol had no effect on GLUT1 protein levels.
      Insulin-like growth factor I (IGF-I; 30 ng/ml) increased the uptake of 3H2-DOG by
      28% in 8 mmol/l glucose-treated cells (P < 0.05) and by 75% in cells switched to
      20 mmol/l glucose for 3 days (P < 0.005). These increases in 3H2-DOG uptake
      occurred despite a lack of effect of IGF-I on GLUT1 protein levels (P > 0.5 vs.
      control). Therefore, hyperglycemia and IGF-I treatment both lead to increases in
      mesangial cell glucose uptake, and hyperglycemia induces increased GLUT1
      expression, which can directly lead to the pathological changes of diabetic
      nephropathy. The effects of high glucose and of IGF-I to stimulate 3H2-DOG uptake
      also appear to be additive.

PMID- 9166677
TI  - Forearm nitric oxide balance, vascular relaxation, and glucose metabolism in
      NIDDM patients.
AB  - Endothelium-dependent and -independent vascular responses were assessed in 10
      NIDDM patients and 6 normal subjects with no evidence of atherosclerotic disease.
      Changes in forearm blood flow and arteriovenous (AV) serum nitrite/nitrate (NO2
      /NO3-) concentrations were measured in response to intra-arterial infusion of
      acetylcholine (ACh) (7.5, 15, 30 microg/min, endothelium-dependent response) and
      sodium nitroprusside (SNP) (0.3, 3, 10 microg/min, endothelium-independent
      response). Insulin sensitivity (determined by minimal model intravenous glucose
      tolerance test) was lower in NIDDM patients (0.82 +/- 0.20 vs. 2.97 +/- 0.29
      10(4) min x microU(-1) x ml(-1); P < 0.01). Baseline forearm blood flow (4.8 +/-
      0.3 vs. 4.4 +/- 0.3 ml x 100 ml(-1) tissue x min(-1); NS), mean blood pressure
      (100 +/- 4 vs. 92 +/- 4 mmHg; NS), and vascular resistance (21 +/- 1 vs. 21 +/- 1
      units; NS), as well as their increments during ACh and SNP, infusion were similar
      in both groups. No difference existed in baseline NO2-/NO3- concentrations (4.09
      +/- 0.33 [NIDDM patients] vs. 5.00 +/- 0.48 micromol/l [control subjects]; NS),
      their forearm net balance (0.31 +/- 0.08 [NIDDM patients] vs. 0.26 +/- 0.08
      micromol/l x 100 ml(-1) tissue x min(-1); NS), and baseline forearm glucose
      uptake. During ACh infusion, both NO2- and NO3- concentrations and net balance
      significantly increased in both groups, whereas glucose uptake increased only in
      control subjects. When data from NIDDM and control groups were pooled together, a
      correlation was found between the forearm AV NO2- and NO3- differences and blood
      flow (r = 0.494, P = 0.024). On the contrary, no correlation was evident between
      NO2- and NO3- concentrations or net balance and insulin sensitivity. In summary,
      1) no difference existed in basal and ACh-stimulated NO generation and
      endothelium-dependent relaxation between uncomplicated NIDDM patients and control
      subjects; 2) in both NIDDM and control groups, forearm NO2- and NO3- net balance
      following ACh stimulation was related to changes in the forearm blood flow; and
      3) ACh-induced increase in forearm blood flow was associated with an increase in
      glucose uptake only in control subjects but not in NIDDM patients. In conclusion,
      our results argue against a role of impaired NO generation and blood flow
      regulation in determining the insulin resistance of uncomplicated NIDDM patients;
      rather, it supports an independent insulin regulation of hemodynamic and
      metabolic effects.

PMID- 9166678
TI  - Modulatory effect of erythrocytes on the platelet reactivity to collagen in IDDM
      patients.
AB  - Platelets participate in the atherothrombotic complications of diabetes. Recent
      data demonstrate that platelet reactivity can be modulated via cell-cell
      interactions with erythrocytes and neutrophils. In this study, platelet
      reactivity was evaluated in 30 IDDM patients. We used an analytical procedure
      that permits an independent evaluation of platelet activation (granule release,
      eicosanoid formation) and platelet recruitment (pro-aggregatory activity of cell
      free releasates) after platelet stimulation with collagen in the presence or
      absence of other blood cells. The interaction between platelets and erythrocytes
      (hematocrit 40%) resulted in a marked enhancement of platelet activation (5HT,
      betaTG, TXA2 release) and recruitment in both patients and control subjects. The
      erythrocyte enhancement of platelet TXA2 synthesis and recruitment was
      significantly higher in the patients, while no differences were detected in
      platelet granule release. The elevated platelet recruitment in the IDDM patients
      was found to be due to 1) increased susceptibility of diabetic platelets to the
      prothrombotic effect of erythrocytes and 2) the greater response of diabetic
      platelets to their own cell-free releasate. Patients with poor metabolic control
      (elevated HbA1c) or longer evolution time had an even greater platelet
      recruitment. The presence of microalbuminuria is not related to the platelet
      recruitment. Since platelet recruitment is an essential step in thrombus growth,
      its enhancement may favor thrombotic complications in IDDM.

PMID- 9166679
TI  - Vitamin E decreases the occurrence of malformations in the offspring of diabetic
      rats.
AB  - An association between excess oxygen radical activity and disturbed embryogenesis
      in diabetic pregnancy has been suggested. In the present study, the protective
      capacity of vitamin E with different treatment regimens was investigated in early
      and late pregnancy of streptozotocin-induced diabetic rats. Daily gavaging of 0.2
      g/kg or 0.8 g/kg of vitamin E exerted moderate protective effects. In contrast,
      treatment with a diet enriched with 2% (wt/wt) of vitamin E, yielding an
      approximate daily dosage of 2 g/kg of vitamin E, clearly restored both embryonic
      and fetal morphology. High-performance liquid chromatography measurement showed
      that maternal diabetes decreased embryonic content of vitamin E. When pregnant
      diabetic animals were supplemented with vitamin E, increased concentrations of
      the vitamin were found in maternal, embryonic, and fetal tissues. Thus, despite
      marked accumulation of vitamin E in maternal tissues, the compound apparently
      reached the conceptus. Thiobarbituric acid reactive substances (TBARS) were
      estimated as a measure of lipid peroxidation, and no changes were observed in
      maternal tissue, embryonic tissue, placenta, and fetal brain in the untreated
      diabetic group. In contrast, a fivefold increase of TBARS was found in fetal
      liver, a rise that was reduced with vitamin E treatment of the diabetic pregnant
      rats and completely normalized with 2% vitamin E in the diet. Congenital
      malformations caused by experimental diabetes can be prevented by antioxidants in
      vivo. These findings further corroborate the notion that an imbalance in the
      metabolism of free oxygen radicals is involved in the embryonic maldevelopment of
      diabetic pregnancy, and suggest a direction for prophylactic treatment in the
      future.

PMID- 9166680
TI  - Genetics of NIDDM in France: studies with 19 candidate genes in affected sib
      pairs.
AB  - As part of an ongoing search for susceptibility loci for NIDDM, we tested 19
      genes whose products are implicated in insulin secretion or action for linkage
      with NIDDM. Loci included the G-protein-coupled inwardly rectifying potassium
      channels expressed in beta-cells (KCNJ3 and KCNJ7), glucagon (GCG), glucokinase
      regulatory protein (GCKR), glucagon-like peptide I receptor (GLP1R),
      LIM/homeodomain islet-1 (ISL1), caudal-type homeodomain 3 (CDX3), proprotein
      convertase 2 (PCSK2), cholecystokinin B receptor (CCKBR), hexokinase 1 (HK1),
      hexokinase 2 (HK2), mitochondrial FAD-glycerophosphate dehydrogenase (GPD2),
      liver and muscle forms of pyruvate kinase (PKL, PKM), fatty acid-binding protein
      2 (FABP2), hepatic phosphofructokinase (PFKL), protein serine/threonine
      phosphatase 1 beta (PPP1CB), and low-density lipoprotein receptor (LDLR).
      Additionally, we tested the histidine-rich calcium locus (HRC) on chromosome 19q.
      All regions were tested for linkage with microsatellite markers in 751
      individuals from 172 families with at least two patients with overt NIDDM
      (according to World Health Organization criteria) in the sibship, using
      nonparametric methods. These 172 families comprise 352 possible affected sib
      pairs with overt NIDDM or 621 possible affected sib pairs defined as having a
      fasting plasma glucose value of >6.1 mmol/l or a glucose value of >7.8 mmol/l 2 h
      after oral glucose load. No evidence for linkage was found with any of the 19
      candidate genes and NIDDM in our population by nonparametric methods, suggesting
      that those genes are not major contributors to the pathogenesis of NIDDM.
      However, some evidence for suggestive linkage was found between a more severe
      form of NIDDM, defined as overt NIDDM diagnosed before 45 years of age, and the
      CCKBR locus (11p15.4; P = 0.004). Analyses of six additional markers spanning 27
      cM on chromosome 11p confirmed the suggestive linkage in this region. Whether an
      NIDDM susceptibility gene lies on chromosome 11p in our population must be
      determined by further analyses.

PMID- 9166681
TI  - Analysis of candidate genes for susceptibility to type I diabetes: a case-control
      and family-association study of genes on chromosome 2q31-35.
AB  - Recent genome searches suggest a putative linkage of many loci to susceptibility
      to type I diabetes. The chromosome 2q31-35 region is reported to be linked to
      susceptibility to type I diabetes and is thought to contain several diabetes
      susceptibility loci. These candidate genes include the HOXD gene cluster, BETA2,
      CTLA4, CD28, IGFBP2, and IGFBP5. Association studies in populations and families
      are required to confirm and/or identify the actual susceptibility loci. We hereby
      report several previously unknown DNA polymorphisms for HOXD8, BETA2, and IGFBP5,
      which we have used along with previously known polymorphisms of HOXD8 and CTLA4
      to test whether these candidate loci are the susceptibility genes on chromosome
      2q31-35. Using a case-control design with a subsequent family-association
      approach to confirm associations, we find no evidence that these candidate genes
      are associated with susceptibility to type I diabetes.

PMID- 9166682
TI  - Polymorphisms in the interleukin-1 gene cluster do not contribute to the genetic
      susceptibility of diabetic nephropathy in Caucasian patients with IDDM.

PMID- 9166683
TI  - Leptin receptor of Zucker fatty rat performs reduced signal transduction.
AB  - Zucker fatty (fa/fa) rats exhibit overt obesity, hypercholesterolemia,
      hyperlipidemia, and hyperglycemia as recessive traits. The fa mutation has been
      determined to be a missense mutation in the extracellular domain of the leptin
      receptor. We report herein the construction of CHO cells that stably express the
      fa-type leptin receptor and the characterization of this receptor using mRNA
      expression levels of the immediate early genes, c-fos, c-jun, and jun-B, which
      are induced by leptin as a criterion of signal transduction. The fa-type receptor
      not only exhibits a slightly reduced leptin-binding affinity, but also performs
      reduced signal transduction.

PMID- 9166684
TI  - Novel mutations and a mutational hotspot in the MODY3 gene.
AB  - Maturity-onset diabetes of the young 3 (MODY3) is a type of NIDDM caused by
      mutations in the transcription factor hepatocyte nuclear factor-1alpha (HNF
      1alpha) located on chromosome 12q. We have identified four novel HNF-1alpha
      missense mutations in MODY3 families. In four additional and unrelated families,
      we observed an identical insertion mutation that had occurred in a polycytidine
      tract in exon 4. Among those families, one exhibited a de novo mutation at this
      location. We propose that instability of this sequence represents a general
      mutational mechanism in MODY3. We observed no HNF-1alpha mutations among 86
      unrelated late-onset diabetic patients with relative insulin deficiency. Hence
      mutations in this gene appear to be most strongly associated with early-onset
      diabetes.

PMID- 9166685
TI  - Leptin suppression of insulin secretion by the activation of ATP-sensitive K+
      channels in pancreatic beta-cells.
AB  - In the genetic mutant mouse models ob/ob or db/db, leptin deficiency or
      resistance, respectively, results in severe obesity and the development of a
      syndrome resembling NIDDM. One of the earliest manifestations in these mutant
      mice is hyperinsulinemia, suggesting that leptin may normally directly suppress
      the secretion of insulin. Here, we show that pancreatic islets express a long
      (signal-transducing) form of leptin-receptor mRNA and that beta-cells bind a
      fluorescent derivative of leptin (Cy3-leptin). The expression of leptin receptors
      on insulin-secreting beta-cells was also visualized utilizing antisera generated
      against an extracellular epitope of the receptor. A functional role for the beta
      cell leptin receptor is indicated by our observation that leptin (100 ng/ml)
      suppressed the secretion of insulin from islets isolated from ob/ob mice.
      Furthermore, leptin produced a marked lowering of [Ca2+]i in ob/ob beta-cells,
      which was accompanied by cellular hyperpolarization and increased membrane
      conductance. Cell-attached patch measurements of ob/ob beta-cells demonstrated
      that leptin activated ATP-sensitive potassium channels (K(ATP)) by increasing the
      open channel probability, while exerting no effect on mean open time. These
      effects were reversed by the sulfonylurea tolbutamide, a specific inhibitor of
      K(ATP). Taken together, these observations indicate an important physiological
      role for leptin as an inhibitor of insulin secretion and lead us to propose that
      the failure of leptin to inhibit insulin secretion from the beta-cells of ob/ob
      and db/db mice may explain, in part, the development of hyperinsulinemia, insulin
      resistance, and the progression to NIDDM.

PMID- 9166686
TI  - Role of the cyclic adenosine monophosphate-dependent protein kinase in the
      control of meiotic resumption in bovine oocytes cultured with thecal cell
      monolayers.
AB  - It has long been known that intracellular levels of cAMP are implicated in the
      process of meiotic resumption in bovine oocytes. The present study was undertaken
      to evaluate the effects of various modulators of cAMP in a coculture system with
      thecal cell monolayers that have been shown to promote meiotic arrest (germinal
      vesicle [GV] stage) in bovine oocytes. Ovaries were obtained from a
      slaughterhouse, and oocytes were collected by puncture of 1- to 5-mm follicles.
      Cumulus-oocyte complexes (COC) were cultured for 18 h in tissue culture medium
      199 supplemented with 10% fetal calf serum and various modulators. When H-89 (N
      [2-(p-bromocinnamylamino)ethyl]-5-isoquinole-sulfonamide) , a protein kinase A
      inhibitor, was used alone, a significant increase (p < 0.05) in the percentage of
      COC maintained in GV stage was observed. In the coculture system with thecal cell
      monolayers that maintained oocytes at the GV stage, H-89 significantly (p < 0.05)
      decreased this percentage. When oocytes were denuded of their cumulus cells, H-89
      (50 microM) alone did not significantly increase the percentage of oocytes
      maintained at the GV stage. In addition, denuded oocytes were not significantly
      maintained at the GV stage when cocultured with thecal cell monolayers. In the
      absence of thecal cell monolayers, a phosphodiesterase inhibitor, 3-isobutyl-1
      methylxanthine (Bx), and an activator of adenylate cyclase, forskolin (Fk),
      significantly increased (p < 0.05) the percentage of denuded oocytes maintained
      at the GV stage. In contrast, Bx-Fk were not effective in maintaining COC at the
      GV stage. The inhibitory effect of H-89 on COC was significantly increased (p <
      0.05) by Bx-Fk. Using thecal cell monolayers with Bx-Fk, the percentage of COC
      maintained at the GV stage was not significantly decreased. These results suggest
      that oocytes were maintained in meiotic arrest by inhibition of cAMP-dependent
      protein kinase by H-89 in cumulus cells. It seems that inhibitory factors
      originating from thecal cells are regulated by a cAMP-dependent protein kinase.
      In turn, inhibitory factors released from thecal cells may regulate a cAMP
      dependent protein kinase in cumulus cells.

PMID- 9166687
TI  - Insulin-like growth factor-1, a component of serum that enables porcine cumulus
      cells to expand in response to follicle-stimulating hormone in vitro.
AB  - The present study was aimed at determining whether insulin-like growth factor-1
      (IGF-1) is a component of fetal bovine serum (FBS) that enables porcine cumulus
      cells to expand in response to FSH in vitro. Cumulus-oocyte complexes (COC)
      obtained from 4- to 6-mm follicles of prepubertal gilts were cultured at 39
      degrees C for 24 h in media that contained human recombinant IGF-1 (50 ng/ml),
      FBS (15% v:v), or their combination, with or without FSH (1.5 microg/ml), and
      cumulus expansion was scored microscopically. Expansion was FSH dependent and was
      observed only when IGF-1, FBS, or both were present. The proportion of FSH
      stimulated COC exhibiting full expansion in response to IGF-1 alone did not
      differ significantly (p > 0.05) from the proportion in those cultured with FBS or
      IGF-1+FBS (79 +/- 2.8% vs. 84 +/- 2.2% or 76 +/- 6.2%, respectively). In a
      concentration-response study, FSH-stimulated expansion was observed in a
      significant proportion of COC (32 +/- 2.8% vs. 0% control) at 1 ng/ml IGF-1, with
      the proportions increasing dose-dependently to maximal values between 10 and 75
      ng/ml IGF-1, and decreasing at higher IGF-1 concentrations. Exposure of COC to an
      IGF-1 receptor (IGF-1R)-neutralizing antibody (Ab) for 90 min before addition of
      FSH and FBS dose-dependently inhibited cumulus expansion, with maximal inhibition
      at 10 microg/ml (1 +/- 1.0% vs. 68 +/- 1.1% control). In the absence of FBS or
      IGF-1, some COC had a tendency toward slight expansion when cultured with FSH,
      and the Ab completely inhibited that effect, suggesting that this may be due to
      endogenous IGF-1 production by the COC. The Ab effect was reversible and was
      eliminated by washing twice with fresh medium followed by culture for an
      additional 24 h in the presence of FSH and FBS. Expression of IGF-1R mRNA in the
      isolated oocyte and cumulus cells was determined by reverse tramscriptase
      polymerase chain reaction using sequence-specific primers. The IGF-1R message was
      detected in both the oocyte and cumulus cells. Collectively, these observations
      suggest that IGF-1 is a component of serum that enables cumulus cells to expand
      in response to FSH in vitro, and that the effect is receptor mediated. Since IGF
      1 is present in the follicle in vivo, it may have a physiological role during
      gonadotropin-induced cumulus expansion.

PMID- 9166688
TI  - Quantified analysis of cortical granule distribution and exocytosis of porcine
      oocytes during meiotic maturation and activation.
AB  - Polyspermy is one of the unresolved problems that exist regarding pig oocytes
      matured and inseminated in vitro. Quantitative study of the changes in the
      cortical granule (CG) population in oocytes is essential for understanding the
      mechanism of how oocytes block polyspermic penetration and for developing the
      optimum conditions for in vitro maturation (IVM) and in vitro fertilization
      (IVF). The present study was conducted to quantify the CG distribution in pig
      oocytes during IVM and IVF by using fluorescein isothiocyanate-labeled peanut
      agglutinin with laser confocal microscopy. The results indicate that CGs are
      distributed in the cortex cytoplasm of oocytes at the germinal vesicle (GV) stage
      with a mean number of 33.8 +/- 7.3 CGs/100 microm2 of cortex. As nuclear
      maturation proceeded to metaphase I and metaphase II, CGs migrated to the cortex
      and formed a continuous monolayer under the oolemma. No distinct CG-free domain
      was observed in oocytes during maturation. The migration of CGs to the cortex
      continued during maturation, with an increased CG density after the GV stage. All
      oocytes penetrated by spermatozoa were activated and released CGs from ooplasm
      with an average residual number of 3.5 +/- 4.6 CGs/100 microm2 of cortex at 18 h
      after insemination. Complete CG exocytosis was observed in 45% of oocytes.
      Calcium ionophore did not induce oocyte nuclear activation, but CGs were released
      from oocytes with an average of 7.1 +/- 4.5 CGs/100 microm2 of cortex still
      present when examined 18 h after treatment. An electrical pulse induced 89% of
      nuclear activation in matured oocytes, and CG exocytosis was observed only in
      nuclear-activated oocytes with an average residual number of 6.4 +/- 9.4 CGs/100
      microm2 of cortex. Complete CG exocytosis was induced by ionophore and electrical
      pulse in 10% and 25% of the oocytes, respectively. These results indicate that
      CGs migrate to the cortex in pig oocytes during IVM and that the matured oocytes
      obtained under these maturation conditions possess the ability to release CGs
      upon sperm penetration, ionophore treatment, and electrical pulse. However, a
      functional block to polyspermic penetration in oocytes after CG exocytosis was
      not fully established in these studies. The present methods and results provide
      the approach for further investigation of the reasons for polyspermy in pig
      oocytes matured and inseminated in vitro.

PMID- 9166689
TI  - Inhibition of monkey sperm hyaluronidase activity and heterologous cumulus
      penetration by flavonoids.
AB  - A microplate assay for hyaluronidase and a heterologous cumulus penetration assay
      were used to determine the effects of four flavonoids (tannic acid, kaempferol,
      quercetin, and apigenin) on the function of cynomolgus monkey sperm. All four
      flavonoids inhibited the activity of hyaluronidase extracted from monkey sperm in
      a concentration-dependent manner over the range of 50-200 microM. Tannic acid and
      apigenin had lower inhibitory effects than kaempferol and quercetin. Kaempferol,
      quercetin, and apigenin at 100 microM were shown to significantly inhibit monkey
      sperm penetration into hamster cumulus. There was a significant linear
      relationship between the capacity of the flavonoids to inhibit monkey sperm
      hyaluronidase activity and their inhibitory effects on hamster cumulus
      penetration (r = 0.97). Tannic acid was observed to reduce sperm motility, and it
      was not used in the cumulus penetration assay. The other three flavonoids tested
      in the cumulus penetration assay did not affect sperm motility, nor did they
      induce acrosome reactions. The results demonstrate that the flavonoids are useful
      tools for assessing the involvement of hyaluronidase in the functions of monkey
      sperm that are involved in fertilization.

PMID- 9166690
TI  - Expression of vascular endothelial growth factor (VEGF) and VEGF-receptor
      messenger ribonucleic acids in the peri-implantation rabbit uterus.
AB  - The endometrial vasculature undergoes expansion during preimplantation stages
      and, even more prominently, after implantation. In addition to angiogenesis,
      vascular hyperpermeability accompanies the attachment and invasion of blastocysts
      into the uterine lining. Vascular endothelial growth factor (VEGF) is an
      angiogenic factor expressed in mammalian uteri that also has potent activity in
      inducing vascular permeability. Rabbit uteri were examined using Northern and in
      situ hybridization to assess the temporal and spatial expression of VEGF and its
      receptor (Flk-1, Flt-1) mRNAs during the pre- and peri-implantation periods (Days
      0-8). Steady-state levels of VEGF mRNA were highest in endometrium at estrous and
      peri-implantation stages (Days 6-8). In situ hybridization revealed a shift from
      uniform expression of VEGF transcripts throughout the uterus at estrus and Day 4,
      to an endometrial epithelial localization just before and during implantation. At
      implantation sites, a pronounced signal was present in the trophoblastic knobs,
      the syncytial aggregates that attach to and invade the endometrium. VEGF protein
      was detected by immunoblot analysis in peri-implantation-stage uteri but was
      below the limit of detection in estrous endometrium. VEGF receptor mRNAs were
      expressed in the uterus at all stages examined, with high levels of Flk-1 and Flt
      1 at estrus and again just before implantation, 6-3/4 days pregnant. The high
      level just before implantation correlates with in situ hybridization results
      showing a prominent, but transient, signal for Flk-1 mRNA in the endometrial
      epithelium. During implantation, Flk-1 mRNA was associated with blood vessels of
      the endometrial stroma. We conclude that VEGF is a candidate factor for the
      induction of vascular hyperpermeability at implantation in the rabbit and in the
      angiogenic process that follows.

PMID- 9166691
TI  - Reproductive condition and the low-dose endotoxin-induced inflammatory response
      in rats. Glomerular influx of inflammatory cells and expression of adhesion
      molecules.
AB  - These experiments were designed to study the increased sensitivity of pregnant
      rats to endotoxin. Pregnant (Pr), cyclic (C), and progesterone (P)-treated
      pseudopregnant rats with or without a decidualized uterus (PSP and DEC rats,
      respectively) received infusions of an ultra-low dose of endotoxin (1.0 microg/kg
      BW) and were killed 3 days later. Pr, PSP, and DEC rats were infused on Day 14, C
      rats on diestrus. Endotoxin-infused rats were compared with saline-infused rats
      in the same reproductive conditions. The inflammatory reaction of the glomeruli
      of the kidneys was studied by immunohistochemical methods using 4-microm cryostat
      sections stained with specific monoclonal antibodies against neutrophils
      (polymorphonuclear cells, PMNs) and monocytes (MOs), and against the adhesion
      molecules ICAM-1 and VCAM-1 on the endothelium, and LFA-1, MAC-1, and VLA-4 on
      the leukocytes. Endotoxin infusion increased glomerular PMN and MO number in Pr,
      PSP, and DEC rats, all of which have elevated P levels, but not in C rats, which
      do not. The endotoxin-induced expression of adhesion molecules, associated with
      this influx of inflammatory cells, varied with the reproductive condition. In C
      rats there was no increased adhesion molecule expression after endotoxin
      treatment, in Pr rats there was increased expression of both the combinations
      ICAM-1/LFA-1 and VCAM-1/VLA-4. DEC rats did not express either of these
      combinations (although there was expression of ICAM-1); PSP rats expressed the
      combination ICAM-1/MAC-1. Adhesion molecule expression thus seems to be regulated
      by ovarian (e.g., P) and placental factors (e.g., of trophoblastic and decidual
      origin). Because the different combinations of adhesion molecules in the various
      reproductive conditions after exposure to endotoxin led to more or less the same
      leukocyte influx under these conditions, the increased sensitivity to endotoxin
      of pregnant individuals cannot be reduced to differences in leukocyte influx into
      the glomeruli.

PMID- 9166692
TI  - Sexually dimorphic activation of midbrain tyrosine hydroxylase neurons after
      mating or exposure to chemosensory cues in the ferret.
AB  - Mating with intromission induces a prolonged preovulatory LH surge in the estrous
      female ferret but inhibits LH secretion in the male. We used the dual
      immunocytochemical localization of Fos (as a marker of neural activation) and
      tyrosine hydroxylase (TH) to determine whether neurons containing norepinephrine
      or other catecholamines are activated after mating. Breeding male ferrets were
      allowed to intromit with estrous females; both animals were perfused 90 min after
      the onset of intromission. Other male and female ferrets were perfused 90 min
      after being placed in a cage in which an opposite-sex ferret in breeding
      condition had previously been housed for 48 h. Control ferrets of each sex were
      perfused 90 min after being placed alone in a clean testing cage. Mating with
      intromission significantly augmented the percentage of TH-immunoreactive (TH-IR)
      neurons colabeled with nuclear Fos-like immunoreactivity (Fos-IR) in both the A6
      and the rostral A2 midbrain catecholamine cell groups in females, but not males.
      Exposure to chemosensory cues alone also increased the percentage of Fos-IR TH
      neurons in the rostral A2, but not the A6, cell group in females. Chemosensory
      cues alone did not affect the percentage of double-labeled neurons in either cell
      group in males. These activated midbrain TH-IR neurons are most likely
      noradrenergic, and their activation in estrous females may facilitate the
      mediobasal hypothalamic release of LHRH required for the preovulatory LH surge.
      In both sexes, mating with intromission, but not chemosensory cues alone,
      augmented the percentage of periglomerular TH-IR neurons in the main olfactory
      bulb (MOB) that were colabeled with Fos-IR. These activated TH-IR neurons in the
      MOB are most likely dopaminergic. Their role in the neural response to mating is
      currently unknown.

PMID- 9166693
TI  - Bovine oviductal and embryonic insulin-like growth factor binding proteins:
      possible regulators of "embryotrophic" insulin-like growth factor circuits.
AB  - Bovine oviductal monolayer and vesicle primary cultures express insulin-like
      growth factor (IGF)-I and -II mRNAs and polypeptides. Early bovine embryos also
      express IGF-I, IGF-II, IGF-I receptor, IGF-II receptor, and insulin receptor
      mRNAs. This study reports the expression of IGF binding protein (IGFBP) mRNAs and
      polypeptides in bovine oviduct primary cultures and IGFBP mRNAs in preattachment
      embryos. Release of immunoreactive IGF-I and IGF-II by oviduct cultures and
      bovine blastocysts was also determined. IGFBP-2, -3, -4, and -5 transcripts were
      observed in oviduct primary cultures throughout an 8-day interval. IGFBP-1 and -6
      mRNAs were consistently not detected in the oviduct. Messenger RNAs encoding
      IGFBPs -2, -3, and -4 were detected throughout bovine preattachment development,
      while transcripts encoding IGFBP-5 were detected only in blastocysts. IGFBP-1 and
      -6 transcripts were not detected in early embryos. Ligand blot analysis with 125I
      labeled IGF-II revealed the presence of four prominent polypeptide bands of
      approximate molecular masses 24, 31, and 36 kDa, and a broad band extending from
      46 to 53 kDa, in conditioned media samples prepared from oviduct primary
      cultures. Western immunoblot analysis confirmed the identity of the 24-kDa, 31
      kDa, and 36-kDa species as IGFBP-4, -5, and -2, respectively. Levels of the
      release of IGF-II from oviductal vesicle cultures were significantly greater than
      levels observed for monolayer cultures (p < 0.005). No significant difference in
      the levels of IGF-I release between monolayer and vesicle cultures was observed.
      Pools of 10 blastocysts released on average 36.2 +/- 3.9 pg of IGF-II per embryo,
      while the release of embryonic IGF-I was below the levels of detection for our
      assay. The results suggest that maternally derived IGF may be regulated by IGFBPs
      to support bovine preattachment development.

PMID- 9166694
TI  - Steroidogenic enzyme expression during preovulatory follicle maturation in pigs.
AB  - During preovulatory maturation, follicles destined to ovulate exhibit a marked
      increase in steroidogenesis, while nonovulatory, steroidogenically inactive
      follicles are lost by atresia. The purpose of this study was to assess the
      expression of the steroidogenic enzymes cytochrome P450 aromatase (P450arom),
      cytochrome P450 17alpha-hydroxylase/C(17-20) lyase (P450c17), and 3beta
      hydroxysteroid dehydrogenase (3betaHSD) and that of the cell proliferation
      associated nuclear antigen Ki-67 by immunohistochemistry in both nonatretic and
      atretic follicles developed during altrenogest-synchronized preovulatory
      maturation. Fifteen cyclic gilts were slaughtered on Days 1, 3, 5 (n = 3 per
      day), and 7 (n = 6) following the withdrawal of altrenogest. Staining intensity
      was assigned a numeric value and was related to follicle size and day following
      altrenogest withdrawal. Follicle atresia was assessed by the extent of in situ 3'
      end-labeling of DNA in apoptotic cells. The overall incidence of atresia was 41%,
      17%, and 7% in small (< 3 mm), medium (3-5 mm), and large (> 5 mm) follicles,
      respectively. Expression of granulosa cell P450arom, Ki-67 antigen, and thecal
      P450c17 was significantly less (p < 0.001) in atretic compared to nonatretic
      follicles. Thecal 3betaHSD was expressed predominantly in medium and large
      nonatretic follicles; expression was nondetectable in 88% of small follicles
      irrespective of follicle health. Ki-67 expression in granulosa cells was greater
      in small and medium nonatretic than in large nonatretic follicles (p < 0.005). In
      large presumptive ovulatory follicles, P450arom was maximally expressed on Days 3
      and 5 and decreased on Day 7 (p < 0.005), while P450c17 was unchanged between
      Days 3 and 7. In contrast, 3betaHSD increased linearly between Days 3 and 7 (p <
      0.005). Staining intensities of P450arom, P450c17, and 3betaHSD were correlated
      with each other and with follicular fluid concentrations of the steroids
      estradiol, androstenedione, and progesterone, whose production they catalyzed.
      These data show that selection of ovulatory follicles is associated with a low
      incidence of apoptosis, a reduction in cell proliferation, maintenance of high
      levels of P450arom, and increased expression of 3betaHSD to provide substrate for
      androgen and estrogen production. During the period of development investigated
      in this study, changes in follicular steroid production in vivo are explained in
      large measure by changes in steroidogenic enzyme expression.

PMID- 9166695
TI  - Estrogen and luminal stimulation of rat uterine kallikrein.
AB  - To understand the regulation of rat uterine kallikrein, we evaluated its
      variations in animals that had been ovariectomized and supplemented with
      estradiol or progesterone, in pseudopregnant animals intraluminally oil
      stimulated or unstimulated, and in unilaterally pregnant animals. The content of
      kallikrein, determined by an RIA highly specific for rK1 (true tissue
      kallikrein), rose in ovariectomized rats with estradiol supplementation (0.28 +/-
      0.03 to 0.44 +/- 0.05 ng/mg) and decreased with progesterone (0.13 +/- 0.02
      ng/mg; n = 15; p < 0.001). Kallikrein content rose from Day 1 of pseudopregnancy
      (PP1) to a maximum on PP7 (0.18 +/- 0.01 to 0.39 +/- 0.04 ng/mg protein; n = 36;
      p < 0.001). On PP7 with unilateral oil intraluminal stimulation, the decidualized
      horn had higher kallikrein content than did the contralateral (0.98 +/- 0.09 vs.
      0.35 +/- 0.05 ng/mg protein; n = 7; p < 0.001). Immunocytochemistry revealed that
      mainly rK1 is localized in the luminal and glandular epithelium, and it increased
      in the stimulated horn. In the unilaterally pregnant rat on Day 7, the fertile
      horn had a higher kallikrein content than its contralateral control (0.71 +/-
      0.07 vs. 0.37 +/- 0.03 ng/mg protein, p < 0.001; n = 8), as well as a higher
      kininogenase activity (239 +/- 34.3 vs. 83.5 +/- 7.9 ng bradykinin(BK)/h per
      horn, p < 0.003; and 945 +/- 90 vs. 585 +/- 40 ng BK/h per gram tissue, p <
      0.002; n = 6). These results indicate that estrogen stimulates, whereas
      progesterone inhibits, kallikrein production, and that hormonal regulation is
      overridden by intraluminal stimulation, thus associating the enzyme with
      decidualization.

PMID- 9166696
TI  - Deoxyribonucleic acid-protein interactions associated with transcriptional
      initiation of the mouse testis-specific cytochrome c gene.
AB  - Transcriptional regulation of the mouse testis-specific cytochrome c (cyt. cT)
      gene was studied by examining DNA-protein interactions in its proximal promoter.
      Testicular and liver nuclear proteins bound to the cyt. cT gene at sites -105 to 
      81, +87 to +113, and +146 to +169, suggesting interactions with ubiquitous
      nuclear proteins. Protein present in liver nuclear extracts bound to a fourth
      site at -176 to -125, whereas protein present in testicular nuclear extracts
      bound to a subregion of this site at -176 to -140. The sequence from -136 to 
      127, bound by liver but not testicular nuclear proteins, is similar to that of
      the binding site of a somatic c-mos repressor protein. Lastly, different nuclear
      proteins from mouse liver and testis bound to a region from -18 to +31 that
      contains a putative Y box at -13 to -2. Mobility shift assays, Southwestern
      blots, and immunoprecipitation studies have established that this putative Y box
      binds a 52-kDa mouse testicular homologue of the Xenopus germ cell-specific Y-box
      protein and a competing 50-kDa protein present in both liver and testis nuclear
      extracts. These data suggest that the testis-specific expression of the mouse
      cyt. cT gene during spermatogenesis may be regulated by the differential binding
      of tissue-specific nuclear proteins to its proximal promoter region.

PMID- 9166697
TI  - A tyrosine-phosphorylated 55-kilodalton motility-associated bovine sperm protein
      is regulated by cyclic adenosine 3',5'-monophosphates and calcium.
AB  - Sperm motility is regulated by protein phosphorylation. We have recently shown
      that a serine/threonine phosphatase system is involved in motility regulation.
      Two of the components of the phosphatase system, GSK-3 and PP1gamma2, are
      regulated by tyrosine phosphorylation. During our investigation of sperm tyrosine
      phosphorylated proteins we discovered a 55-kDa protein whose tyrosine
      phosphorylation correlates closely to the motility state of sperm. This protein
      is tyrosine phosphorylated to a much higher degree in motile caudal than in
      immotile caput epididymal sperm. Motility inhibition of caudal epididymal sperm
      by protein kinase A (PKA) anchoring inhibition or by ionomycin-induced calcium
      overload led to the virtual disappearance of tyrosine phosphorylation of the 55
      kDa protein. Conversely, treatment of sperm with motility activators,
      isobutylmethylxanthine or 8-bromo-cAMP, resulted in increased tyrosine
      phosphorylation of the protein. The protein was present in the soluble 100 000 x
      g supernatants of sperm extracts and was heat labile. Chromatography through
      diethylaminoethyl-cellulose and Western blot analysis showed that this 55-kDa
      protein is not a regulatory subunit of PKA or alpha-tubulin. Our results
      represent the identification of a soluble protein whose tyrosine phosphorylation
      varies directly with motility and suggest that motility regulation may involve
      cross talk between PKA, calcium, and tyrosine kinase pathways.

PMID- 9166698
TI  - Insulin-like growth factor-binding protein-2 and -3: their biological effects in
      bovine thecal cells.
AB  - This study was aimed at testing the hypothesis that the insulin-like growth
      factor-binding proteins (IGFBP)-2 and -3 can modulate the hormone-dependent
      differentiation of thecal cells in vitro. Thecal cells from large (> or = 8 mm)
      follicles were collected from cattle, cultured for 2 days in medium containing
      10% fetal calf serum, washed, and then treated for an additional 2 days in serum
      free medium with bovine LH (100 ng/ml), recombinant human insulin-like growth
      factor (IGF)-I (0 or 30 ng/ml), recombinant human IGFBP-2 (0, 200, or 400 ng/ml;
      i.e., 0, 6.5, or 12.9 nM), or recombinant human IGFBP-3 (0, 200, or 400 ng/ml;
      i.e., 0, 4.3, or 8.5 nM). IGFBP-2 (200 and 400 ng/ml) inhibited (p < 0.05) IGF-I
      induced androstenedione production by 18-30% but did not influence (p > 0.10)
      progesterone production or thecal cell proliferation in the presence of LH and/or
      IGF-I. In contrast, IGFBP-3 (200 ng/ml) inhibited the IGF-I-induced increase in
      thecal cell numbers by 76%, and thecal cell progesterone and androstenedione
      production by 52% and 89%, respectively. A higher dose of IGF-I (i.e., 100 ng/ml)
      overcame the inhibitory effects of IGFBP-3 on IGF-I-induced cell proliferation
      and on progesterone and androstenedione production by thecal cells. As with IGFBP
      2, IGFBP-3 had no effect (p > 0.10) on LH-induced progesterone or androstenedione
      production by thecal cells in the absence of IGF-I. Both IGFBP-2 and IGFBP-3
      directly inhibited [125I]IGF-I and -II binding to thecal cells; IGFBP-2 was a
      weaker inhibitor of thecal [125I]IGF-I and -II binding than IGFBP-3. These
      results indicate that IGFBP-3 has a more pronounced inhibitory effect than IGFBP
      2 on IGF-I action in cultured bovine thecal cells. Thus, IGFBP-3 may play a more
      significant role than IGFBP-2 in regulating thecal cell proliferation and
      steroidogenesis during follicular development in cattle.

PMID- 9166699
TI  - Expression of messenger ribonucleic acid (mRNA) encoding 3beta-hydroxysteroid
      dehydrogenase delta4,delta5 isomerase (3beta-HSD) during recruitment and
      selection of bovine ovarian follicles: identification of dominant follicles by
      expression of 3beta-HSD mRNA within the granulosa cell layer.
AB  - The objective of the present study was to examine changes in expression of mRNA
      encoding 3beta-hydroxysteroid dehydrogenase delta4,delta5 isomerase (3beta-HSD)
      during recruitment and selection of bovine ovarian follicles. Dairy heifers (4
      5/time period) were ovariectomized at 12, 24, 36, 48, 60, 72, 84, or 96 h after
      initiation of the first follicular wave (Time 0) following estrus. Expression of
      3beta-HSD mRNA was localized by in situ hybridization and quantified by image
      analysis. Expression of 3beta-HSD mRNA was first detected in theca interna cells
      of preantral follicles with a well-developed theca layer and in granulosa cells
      of follicles > or = 8 mm in diameter. Regardless of stage of follicular wave,
      expression of 3beta-HSD mRNA in granulosa cells of follicles > or = 8 mm was
      correlated with follicular size (r = 0.665; p < 0.01). The 36-h time period
      appeared to be a transition period for selection since dominant follicles were
      detected by size and expression of 3beta-HSD mRNA in some cows but not in others.
      By 48 h after wave initiation, dominant follicles could be identified by both
      size and expression of 3beta-HSD mRNA. Expression of mRNA for 3beta-HSD in theca
      cells was higher (p < 0.05) at 24 h than at 12 h and remained elevated thereafter
      through 96 h. In contrast to theca cells, expression of mRNA for 3beta-HSD was
      undetectable within granulosa cells at 12 and 24 h. At 36 h, 3beta-HSD mRNA was
      expressed in granulosa cells of healthy follicles > or = 8 mm, and expression was
      higher (p < 0.05) at 48 h compared with 36 h. Expression of 3beta-HSD mRNA levels
      increased further in granulosa cells (p < 0.05) at 84 and 96 h compared to 48 h.
      Upon detection of mRNA for 3beta-HSD in granulosa cells, high levels of
      expression were always found in one (dominant) follicle/cow with the exception of
      two cows at 36 and 84 h that expressed 3beta-HSD mRNA in two large healthy
      follicles. Expression of 3beta-HSD mRNA was also detectable in granulosa cells of
      a few large atretic follicles in which remnant granulosa cells appeared to be
      luteinized. Healthy follicles expressed higher (p < 0.05) levels of 3beta-HSD
      mRNA in both theca and granulosa cells than did atretic follicles. Expression of
      3beta-HSD mRNA in theca cells was higher (p < 0.01) in dominant follicles than in
      other subordinate healthy follicles. These results indicate that only selected
      dominant follicles express 3beta-HSD mRNA within granulosa cells, and expression
      increased in both thecal and granulosa cells during the follicular wave.
      Therefore, expression of 3beta-HSD mRNA within granulosa cells may be associated
      with the mechanism of selection of the dominant follicle during a follicular wave
      and may be required for maximum steroid production during follicular dominance.

PMID- 9166700
TI  - Expression of cdc25 phosphatases in the germ cells of the rat testis.
AB  - cdc25A and cdc25C, which encode threonine/tyrosine phosphatases involved in cell
      cycle regulation, were found to be differentially localized in rat testicular
      germ cells during spermatogenesis. Northern blot analysis identified two cdc25A
      transcripts. A transcript of 3.8 kilobases (kb) was expressed in the early germ
      cells including spermatogonia, and a 3.3-kb transcript was highly expressed in
      spermatocytes and round spermatids. In situ hybridization showed that the levels
      of mRNA for cdc25A were highest in diplotene spermatocytes and round spermatids
      but were undetectable in Sertoli cells. Both transcripts for cdc25A increased
      with retinol treatment in the vitamin A-deficient testis. Immunolocalization
      showed that cdc25A protein was distributed in the cytoplasm of germ cells,
      whereas cdc25C was localized to the nucleus of late spermatocytes and round
      spermatids. Previous studies have identified two cdc25C transcripts of 2.1 kb and
      1.9 kb, which were expressed in spermatocytes and round spermatids, respectively.
      These results suggest that cdc25A may function during mitosis of spermatogonia.
      Both cdc25A and cdc25C may function in the regulation of the meiotic cell cycle,
      although in different manners, as indicated by their subcellular localization.

PMID- 9166701
TI  - Contributions of endogenous inhibin and estradiol to the regulation of follicle
      stimulating hormone and luteinizing hormone secretion in the pregnant rat.
AB  - To examine the contributions of endogenous inhibin and estradiol to the
      regulation of FSH and LH secretion in the pregnant rat, some rats were passively
      immunized against inhibin and/or estradiol, and others were ovariectomized, on
      Days 5, 10, 15, and 20 of pregnancy. Ovarian and uterine venous blood was
      collected separately to confirm the sources of inhibin and steroid hormones
      during pregnancy. Immunoreactivity of inhibin in the placenta was also examined
      by RIA. Levels of inhibin in ovarian venous plasma were significantly higher than
      those in peripheral plasma during pregnancy. No difference was observed between
      the levels of inhibin in uterine venous plasma and peripheral plasma. No
      immunoreactivity of inhibin was detected in placental homogenate from rats at
      Days 10, 15, and 20. FSH secretion significantly increased after
      immunoneutralization of inhibin during pregnancy. A marked increase in FSH
      secretion was noted on Days 5 and 20, and the smallest increase was observed on
      Day 15. Administration of estradiol antiserum (AS) alone did not induce a
      significant increase in FSH secretion on any day of pregnancy. However, a
      synergistic effect of estradiol AS and inhibin AS was observed on Day 20. On Days
      5, 10, and 20, administration of inhibin AS or estradiol AS induced a significant
      increase in LH secretion. A synergistic effect of inhibin AS and estradiol AS on
      LH secretion was observed on Day 5. On Days 5 and 10, significantly high LH
      secretion was noted in ovariectomized rats as compared with that in rats treated
      with both inhibin AS and estradiol AS, indicating that other ovarian hormones
      such as progesterone may be involved in the suppression of LH secretion in these
      stages of pregnancy. These data indicate that both inhibin and estradiol,
      predominantly secreted from the ovary, are involved in the regulation of
      gonadotropin secretion during pregnancy as during the estrous cycle in the rat.

PMID- 9166702
TI  - Induction of apoptosis in the germ cells of adult male rats after exposure to
      cyclophosphamide.
AB  - Treatment with cyclophosphamide, a commonly used anticancer drug, may result in
      oligozoospermia or azoospermia. The objective of this study was to determine
      whether exposure of male rats to cyclophosphamide induces apoptosis in male germ
      cells, and if so, when the peak of apoptosis occurs and at what specific stages
      of spermatogenesis. The presence of apoptosis was determined by terminal
      deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) detection in
      situ and by an increase in DNA fragmentation (DNA ladder). To determine the time
      course of drug-induced apoptosis, male Sprague-Dawley rats were treated with a
      single dose (70 mg/kg BW) of cyclophosphamide, and the testes were fixed 0, 4, 8,
      12, 18, 24, and 48 h after treatment. To determine the dose response, rats were
      treated with doses of cyclophosphamide (0, 2, 7, 20, and 70 mg/kg), and the
      testes were fixed 12 h after treatment. A low spontaneous incidence of apoptosis
      was observed in controls, in particular in premeiotic germ cells of stages I-IV
      and XI-XIV of the seminiferous tubules. In cyclophosphamide-exposed rats, the
      incidence of apoptosis increased progressively at 4 h and 8 h, reached a peak at
      12 h (about 3.5-fold above control), and then decreased rapidly to control levels
      by 48 h. A 70-mg/kg dose of cyclophosphamide induced a significant increase in
      apoptosis; lower doses did not. Although drug-induced apoptosis occurred in all
      stages of germ cells, it was most pronounced in spermatogonia and spermatocytes
      in stages I-IV and XI-XIV. Thus, apoptosis may be involved in the occurrence of
      oligozoospermia or azoospermia after cyclophosphamide treatment. Apoptosis of
      damaged premeiotic germ cells may serve a critical role in protecting subsequent
      generations from the diverse effects of toxicants.

PMID- 9166703
TI  - Alterations to the pituitary-gonadal axis in the peripubertal female rat exposed
      in utero and through lactation to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) is
      a potent disrupter of vertebrate endocrine systems. It was shown previously that
      in utero and lactational (IUL) exposure to TCDD resulted in a reduction in serum
      estradiol concentrations; however, the mechanism for this remains unknown. In the
      current study, the effects of perinatal exposure to TCDD on the pituitary-ovarian
      axis were examined. Pregnant rats were given a single oral dose of 1 microg
      TCDD/kg or vehicle as control on gestation Day 15, and female pups were killed on
      postnatal Day 21. Pituitaries were assayed for gonadotropin beta-subunit mRNA;
      additional pituitaries were cultured for 4 h and the media were assayed for FSH.
      Gonadotropin receptor mRNAs from vehicle- and TCDD-exposed animals were compared,
      with some ovaries cultured and the media assayed for estrogen secretion. LH, FSH,
      progesterone, and androstenedione concentrations were determined in serum. IUL
      exposure to TCDD resulted in a significant reduction of pituitary FSHbeta mRNA.
      Although estrogen output was shown to be reduced, neither serum FSH nor LH
      concentration was increased significantly, and FSH secretion in vitro was not
      altered. Similarly, serum progesterone and androstenedione were not altered by
      TCDD exposure, while in vitro estrogen secretion was significantly reduced. These
      data suggest that TCDD did not act on serum gonadotropin concentrations. The
      reduction in the concentration of serum estrogen appears to result from direct or
      indirect actions on the ovary at some point following androstenedione production.

PMID- 9166704
TI  - Depletion of glutathione during bovine oocyte maturation reversibly blocks the
      decondensation of the male pronucleus and pronuclear apposition during
      fertilization.
AB  - Oocyte-produced glutathione (the tripeptide gamma-glutamyl-cysteinyl-glycine;
      GSH) has been implicated in the reduction of disulfide bonds in the sperm nucleus
      during fertilization and thus in the development of the male pronucleus (PN). In
      this study, we show that the depletion of endogenous glutathione by 10 mM
      buthionine sulfoximine (BSO; specific inhibitor of GSH synthesis) during bovine
      oocyte maturation (24 h in vitro; represents prophase I to metaphase II
      transition in this species) blocks the formation of a male PN in > 85% of treated
      oocytes (vs. 6.8% in controls) and prevents the assembly of the sperm aster
      microtubules in approximately 35%. Consequently, the pronuclear migration and
      apposition do not occur. Ultrastructural observations suggest that the effect of
      BSO on pronuclear apposition might be due to incomplete disassembly of the sperm
      tail connecting piece, which normally leads to the release of the sperm centriole
      and to the reconstitution of the zygotic centrosome during fertilization. The
      sperm nucleus decondensation and migration blocks were reversed by the treatment
      of the GSH-depleted oocytes with 1-10 mM dithiothreitol (a disulfide bond
      reducing agent) applied 8 h after insemination: 82% of these oocytes exhibited a
      normal male PN and pronuclear apposition 20 h after insemination. The pool of
      glutathione seems to be generated during oocyte maturation since > 80% of oocytes
      that were matured in the absence of BSO displayed a normal male PN, as apposed to
      a female PN, when inseminated and cultured in the presence of 10 mM BSO. These
      data suggest that the reduction of disulfide bonds in the sperm after
      incorporation is important for the formation of the male PN, as well as for the
      disassembly of the sperm tail connecting piece and pronuclear apposition. The
      lack of disulfide-reducing power in the GSH-depleted oocytes can be reversed by
      treatment with disulfide bond-reducing agents.

PMID- 9166705
TI  - Type I and type II interleukin-1 receptor expression in rat, mouse, and human
      testes.
AB  - Despite clear indications of interleukin-1 (IL-1) action on Sertoli and germ
      cells, previous studies failed to detect IL-1 receptors (IL-1R) within the
      seminiferous tubules. Here, we investigated the existence of the type I signaling
      receptor (IL-1RI) and the type II decoy receptor (IL-1RII) mRNAs within the
      testis. Polymerase chain reaction analysis showed the presence of both receptor
      mRNAs in isolated rat, mouse, and human somatic testicular cells (macrophages,
      Leydig, Sertoli, and peritubular cells). While also present in rat and mouse
      isolated pachytene spermatocytes and early spermatids, these receptor mRNAs were
      not found in human germ cells. The distribution of both IL-1R mRNAs was then
      examined in adult rat and mouse testis using light and electron microscopic in
      situ hybridization. No IL-1RI signal was detected in rat testis. In mouse testis,
      we did not find any signal for IL-1RII. In contrast, IL-1RI mRNA was detected in
      a wide variety of mouse testicular cells. Strong expression was observed in the
      rete testis area and high expression was seen over the epithelium of the
      epididymal duct and in interstitial cells, while lower labeling was detected in
      peritubular and Sertoli cells and in all germ cell types from spermatogonia to
      early spermatids; no signal was seen in late spermatids. That the IL-IR was also
      strongly expressed in the interstitium, the rete testis and efferent duct areas,
      and the epididymis was established using an autoradiography technique. Overall,
      our study strongly supports the hypothesis that IL-1 is a regulator of testicular
      function of prime importance.

PMID- 9166706
TI  - Immunolocalization of acidic and basic fibroblast growth factors in porcine
      uterine and conceptus tissues.
AB  - Immunohistochemical techniques were used to localize acidic and basic fibroblast
      growth factor (FGF) polypeptides in porcine uterine and conceptus tissues
      collected on Days 10 through 14 of gestation, which is the peri-implantation
      period, and in uterine tissues collected on the same days of the estrous cycle.
      Our results demonstrate differential expression of acidic and basic FGF (aFGF,
      bFGF) in porcine uterine and conceptus tissues. Localization of these peptides in
      the uterus of cycling and pregnant pigs was different from that reported for
      other species, suggesting species-specific roles for FGFs in early pregnancy.
      Increases in both cytoplasmic and nuclear bFGF immunostaining were detected in
      uterine luminal and glandular epithelial cells from Days 10 to 14 of gestation
      but not in the uterine epithelium of cycling pigs. Acidic FGF immunostaining was
      not detected in luminal or glandular epithelium of either cycling or pregnant
      uterine tissue; however, differential stromal staining was observed. Uterine
      tissues collected from pigs on Days 10-14 of the estrous cycle had diffuse aFGF
      immunostaining throughout the stroma. During early pregnancy, however, intense
      aFGF immunostaining was concentrated around the glandular epithelial and below
      the luminal epithelial cells as gestation progressed. Basic FGF, but not aFGF,
      was detected in porcine conceptuses collected during the peri-implantation period
      (Days 10-14 of gestation). Although both acidic and basic FGF belong to the same
      family of proteins, results of the present study indicate that they likely play
      different roles in uterine function and conceptus development in pigs.

PMID- 9166707
TI  - Effects of bovine follicular fluid and passive immunization against gonadotropin
      releasing hormone (GnRH) on messenger ribonucleic acid for GnRH receptor and
      gonadotropin subunits in ovariectomized ewes.
AB  - In cultured ovine pituitary cells, inhibin increases concentrations of mRNA
      encoding GnRH receptor and numbers of GnRH receptors. The objective of this study
      was to test the hypothesis that inhibin increases concentrations of ovine GnRH
      receptor mRNA in vivo. Ovariectomized ewes were used to eliminate effects of
      endogenous ovarian hormones, and passive immunization against GnRH was employed
      to avoid possible confounding influences of GnRH on GnRH receptor gene
      expression. Two groups of ewes (n = 5/group) were treated with 50 ml GnRH
      antiserum on Days 0 and 3 of the experiment. One group of immunized ewes received
      10 ml charcoal-extracted bovine follicular fluid (bFF) as a source of inhibin
      every 8 h for 48 h on Days 4-6 of the experiment. A third group of ewes was not
      passively immunized and was treated only with bFF, and control ewes received no
      treatments. Anterior pituitary glands were collected from all ewes on Day 6.
      Passive immunization against GnRH, alone or in combination with treatment with
      bFF, decreased mean concentrations of LH (p < 0.01) and LH pulse amplitude (p <
      0.001). In ewes treated only with GnRH antiserum, number of LH pulses was also
      reduced (p < 0.03). Circulating concentrations of FSH tended to be lower (p =
      0.06) in passively immunized ewes compared to controls. Treatment with bFF, alone
      or in combination with GnRH antiserum, reduced circulating concentrations of FSH
      (p < 0.02) and amounts of FSHbeta subunit mRNA (p < 0.001) to less than 30% and
      10% of control values, respectively. Despite effects of bFF on concentrations of
      FSHbeta mRNA and secretion of FSH, concentrations of GnRH receptor mRNA were
      similar among controls, ewes treated with bFF alone, and passively immunized ewes
      treated with bFF. Passive immunization against GnRH did not affect concentrations
      of GnRH receptor mRNA but resulted in a reduction (p < 0.05) in amount of LHbeta
      mRNA. Treatment with bFF did not affect amounts of either alpha subunit or LHbeta
      subunit mRNA except when combined with treatment with antiserum, when amounts of
      both alpha and LHbeta subunit mRNA were reduced (p < 0.05). These results do not
      support the hypothesis that inhibin increases concentrations of GnRH receptor
      mRNA in the ewe, and they provide evidence that inhibin is not an acute regulator
      of ovine GnRH receptor gene expression in vivo.

PMID- 9166708
TI  - Estradiol acts locally within the retrochiasmatic area to inhibit pulsatile
      luteinizing-hormone release in the female sheep during anestrus.
AB  - In the present study we have identified a site of action of estradiol in the
      inhibition of LH secretion during anestrus in the ewe. In the first experiment,
      we studied six sites: the medial preoptic area, the lateral preoptic area, the
      ventromedial hypothalamus, the ventrolateral hypothalamus, the retrochiasmatic
      area (RCh), and the periventricular posterior hypothalamus. We compared the
      changes in parameters of pulsatile LH secretion (interpulse interval, mean nadir,
      mean amplitude, and mean area under curve) during three 6-h sampling periods:
      before and 30-36 h and 9 days after intracerebral implantation of crystalline
      estradiol. Animals that received estradiol in the RCh (n = 5) showed a
      significantly greater increase in both the intervals between pulses of LH (up
      116%, p < 0.03) and the area under the curve (up 180%, p < 0.01) than any of the
      other groups of 7 animals. In the second experiment, implantation of estradiol in
      the RCh (n = 6) induced an increase in the intervals between pulses of LH (p <
      0.03), whereas receiving an empty implant (n = 6) had no effect, showing that
      estradiol specifically induced increases in the intervals between pulses. Thus,
      estradiol appears to act in the RCh where the dopaminergic A15 nucleus, known to
      inhibit pulsatile LH release, is located.

PMID- 9166709
TI  - Organic osmolytes and embryos: substrates of the Gly and beta transport systems
      protect mouse zygotes against the effects of raised osmolarity.
AB  - Mouse embryo development is identically inhibited by raised osmolarity, whether
      produced by added NaCl or raffinose, demonstrating that high osmolarity is itself
      detrimental to embryos. In the face of increased osmolarity, cells in the brain
      and kidney, and likely many other cells, accumulate nonperturbing organic
      osmolytes in their cytoplasm. In the presence of any of a number of organic
      compounds that were proven or probable substrates of either the Gly or the beta
      transport systems, mouse embryo development in vitro was protected from raised
      osmolarity. Zygotes developed past the "2-cell block," and with most Gly or beta
      substrates, to the blastocyst stage. The most effective osmoprotectants were
      glycine, glutamine, betaine, proline, beta-alanine, and hypotaurine; several
      others were partially effective. A model Gly substrate, glycine, was effective at
      a much lower concentration (EC50 = 50 microM) than was a model beta substrate,
      beta-alanine (EC50 = 1.3 mM). The protective effect of these two compounds was
      additive, indicating a common mode of action. The various effective compounds
      tested do not all share metabolic pathways or other such properties in common.
      Thus, it is likely that cleavage-stage mouse embryos utilize them, in large part,
      as organic osmolytes.

PMID- 9166710
TI  - Effects of inhibin A and activin A during in vitro maturation of bovine oocytes
      in hormone- and serum-free medium.
AB  - The aim of this study was to investigate whether inhibin A and/or activin A play
      a role in the acquisition of oocyte competence during the final stages of
      oogenesis. The particular goal was to establish whether inhibin A and activin A
      exert development-enhancing effects during in vitro maturation in serum-free
      media and whether such effects are related to changes in the kinetics of meiotic
      resumption and/or fertilization rates. Cumulus-oocyte-complexes (COCs) were
      matured in two control media (Medium 199 [M199] with hormones and serum, hormone
      serum control; M199 + 0.6% BSA, BSA-control) and nine treatment media (M199 with
      0.6% BSA containing 100, 10, and 1 ng/ml of recombinant human inhibin A,
      recombinant human activin A, and the combination of the two). Oocytes were
      fertilized and cultured using standard procedures. Cleavage was assessed at 54 h
      and blastocyst development at 8 days after in vitro fertilization. Kinetics of
      oocyte maturation and the fertilization rates were evaluated after fixing and
      staining (Hoechst 33342) of oocytes at 8, 16, and 22 h after onset of in vitro
      maturation or of presumptive zygotes at 12 h after in vitro fertilization,
      respectively. Although there was no effect on cleavage rates, inhibin A and
      activin A significantly enhanced postcleavage development at concentrations of 10
      ng/ml (57.7 +/- 7.5% and 56.6 +/- 11.7%, respectively) and 100 ng/ml (50.6 +/-
      18.6% and 56.4 +/- 4.0%, respectively) compared to that in the BSA-control group
      (24.6 +/- 3.2%). Whereas inhibin A- and activin A-treated oocytes showed
      development-enhancing effects similar to those in the hormone-serum controls,
      these groups differed with regard to the kinetics of meiotic resumption.
      Likewise, the enhanced development of the hormone-serum control and the inhibin
      A/activin A-treated oocytes was not related to increased fertilization rates
      relative to the BSA-control. These results suggest that inhibin A and activin A
      may play important roles during the final stages of oogenesis and that
      recombinant inhibins and activins are useful compounds for the development of a
      serum-free culture system for in vitro maturation of oocytes from cattle and
      possibly other mammalian species.

PMID- 9166711
TI  - Ovarian activin receptor subtype and follistatin gene expression in rats:
      reciprocal regulation by gonadotropins.
AB  - The production of activin, follistatin (FS), and inhibin, proteins present in the
      ovary and involved in mammalian reproduction, is regulated by gonadotropins and
      estradiol. We report here gonadotropin regulation of ovarian activin receptor
      (ActR) subtype and FS mRNAs. Expression of ActRI, ActRIIA, ActRIIB, and FS mRNA
      was measured on the afternoon of proestrus (1800 h) and the morning of estrus
      (0800 h). ActRI and ActIIA subtype mRNA concentrations fell by approximately 50%
      (p < 0.05) following the proestrous gonadotropin surge (ActRIIB mRNA was
      undetectable), while FS mRNA was unchanged. To define the contribution of
      gonadotropins, hypophysectomized (HYPOX) female rats were given recombinant human
      (rh) FSH and hCG, which decreased both ActR mRNAs (by approximately 70% and
      aproximately 50% for ActRI and IIA, respectively) and increased FS mRNA by 2
      fold. As gonadotropins could act via estradiol (E2), HYPOX rats were given E2;
      ActRI was decreased, but ActRIIA mRNA was increased. The actions of gonadotropins
      were preferential, as the combination of rhFSH and hCG with E2 reduced ActRIIA
      mRNA. FS mRNA was increased to a similar degree by E2 and/or gonadotropins. These
      data suggest that gonadotropins regulate ActR and FS gene expression via multiple
      mechanisms. Both a direct action on ActRIIA (inhibition) and an indirect action
      through E2 on ActRI (inhibition) and FS (stimulation) suggest potential
      physiologic mechanisms for the reciprocal regulation of ActR subtype and FS
      mRNAs.

PMID- 9166712
TI  - Determination of testis temperature rhythms and effects of constant light on
      testicular function in the domestic fowl (Gallus domesticus).
AB  - There is a wide range of opinions regarding the operating temperature of the
      testis in the domestic fowl. We used physiological monitoring techniques to
      investigate testis and body temperature over daily periods and under various
      light regimes to elucidate body temperature gradients in the fowl. We confirm
      that the operating temperature of the adult fowl's testes is equivalent to core
      body temperature (40-41 degrees C). Long-term continuous temperature monitoring
      showed that there was no difference between the temperature of the testis, liver,
      and peritoneum during a 24-h period either in a normal light:dark cycle or under
      constant light conditions. However, there was a slight decrease in all
      temperatures at subjective night in each case, a decrease that does not appear to
      be sufficient to influence spermatogenesis. Birds maintained under constant light
      throughout two cycles of the seminiferous epithelium (28 days) still exhibited
      normal testis function and structure, even when "nightly" testis temperature
      decrease was the lowest. Thus, by undergoing spermatogenesis at an elevated
      temperature, the domestic fowl system is unique among the homeothermic animal
      systems studied to date.

PMID- 9166713
TI  - Down-regulation of oxytocin receptors and secretion of prostaglandin F2alpha
      after chronic treatment of ewes with estradiol-17beta.
AB  - Experiments were conducted to investigate the mechanisms through which chronic
      treatment with estradiol-17beta (E2) prolongs the estrous cycle in the ewe. To
      determine whether treatment with estradiol maintained the corpus luteum (CL),
      mature ewes were assigned randomly to two groups receiving s.c. injections of
      either 500 microg E2 in corn oil or vehicle alone for 20 days beginning on Day 4
      of the cycle (n = 5 per group). Laparotomy of E2-treated ewes on Day 24 revealed
      the presence of CL previously marked with India ink on Day 7 of the cycle.
      Treatment increased the mean interestrous interval for 4 of 5 animals compared
      with that of controls (p < 0.001). Therefore, to determine whether the increase
      in the interestrous interval was due to an effect on the function and/or
      concentration of uterine oxytocin receptors (OTr), ewes (n = 5 per group) were
      injected with 500 microg E2 or vehicle as described above from Days 4 to 14 of
      the cycle. On Day 15, a jugular blood sample was collected for progesterone (P4)
      analysis, after which ewes were given an i.v. injection of oxytocin (OT; 20 IU
      USP) or saline, and blood samples were collected at frequent intervals for 60 min
      to determine plasma concentrations of 13,14-dihydro-15-ketoprostaglandin F2alpha
      (PGFM). Laparotomies were performed after blood collection to remove uterine
      endometrium for OTr analysis. Mean serum concentrations of P4 were greater in
      treated than in control ewes on Day 15 (p < 0.05). Treatment of ewes with E2
      prolonged luteal function and resulted in reduced uterine concentration of OTr
      compared with that of controls (p = 0.002). Treatment with E2 reduced OT-induced
      plasma concentrations of PGFM compared with controls (p < 0.01). Collectively,
      these data suggest that chronic treatment of ewes with estradiol during the cycle
      can prolong the interestrous interval by reducing uterine concentration of OTr
      and hence OT-induced secretion of prostaglandin.

PMID- 9166714
TI  - Nitric oxide-mediated mitochondrial damage in the brain: mechanisms and
      implications for neurodegenerative diseases.
AB  - Within the CNS and under normal conditions, nitric oxide (.NO) appears to be an
      important physiological signalling molecule. Its ability to increase cyclic GMP
      concentration suggests that .NO is implicated in the regulation of important
      metabolic pathways in the brain. Under certain circumstances .NO synthesis may be
      excessive and .NO may become neurotoxic. Excessive glutamate-receptor stimulation
      may lead to neuronal death through a mechanism implicating synthesis of both .NO
      and superoxide (O2.-) and hence peroxynitrite (ONOO-) formation. In response to
      lipopolysaccharide and cytokines, glial cells may also be induced to synthesize
      large amounts of .NO, which may be deleterious to the neighbouring neurones and
      oligodendrocytes. The precise mechanism of .NO neurotoxicity is not fully
      understood. One possibility is that it may involve neuronal energy deficiency.
      This may occur by ONOO- interfering with key enzymes of the tricarboxylic acid
      cycle, the mitochondrial respiratory chain, mitochondrial calcium metabolism, or
      DNA damage with subsequent activation of the energy-consuming pathway involving
      poly(ADP-ribose) synthetase. Possible mechanisms whereby ONOO- impairs the
      mitochondrial respiratory chain and the relevance for neurotoxicity are
      discussed. The intracellular content of reduced glutathione also appears
      important in determining the sensitivity of cells to ONOO- production. It is
      concluded that neurotoxicity elicited by excessive .NO production may be mediated
      by mitochondrial dysfunction leading to an energy deficiency state.

PMID- 9166715
TI  - Protein kinase A coordinately regulates both basal expression and cyclic AMP
      mediated induction of three catecholamine-synthesizing enzyme genes.
AB  - Studies have shown that the cyclic AMP-regulated pathway is involved in the
      activation of tyrosine hydroxylase (TH) and in the induction of gene expression
      of the three catecholamine-synthesizing enzymes, TH, dopamine beta-hydroxylase
      (DBH), and phenylethanolamine N-methyltransferase (PNMT). In the present study we
      investigated further the role of protein kinase A (PKA) in the regulation of both
      basal and cyclic AMP-inducible transcription of the three catecholamine
      synthesizing enzymes in primary cultured bovine chromaffin cells by using the PKA
      specific inhibitor N-[2-(p-bromocinnamylamine)ethyl]-5-isoquinolinesulfonamide (H
      89). In the presence of 40 microM H-89, mRNA levels of TH, DBH, and PNMT were
      reduced to 17 +/- 8, 19 +/- 8, and 14 +/- 2% of the untreated control,
      respectively, in 24 h, and intracellular norepinephrine and epinephrine levels
      were decreased to 20 and 34%, respectively, in 72 h. At 20 microM, although the
      basal enzyme gene expression levels were little affected, their induction by
      forskolin was abolished and norepinephrine and epinephrine levels fell to 55 and
      74%. This reduction in catecholamines at 20 microM was probably due to changes in
      the phosphorylation state of TH, as its enzymatic activity was found to be
      decreased to 66 and 69% in 48 and 72 h, respectively. Thus, PKA activity in
      bovine adrenal medullary cells coordinately regulates both basal and cyclic AMP
      inducible gene expression of specific catecholamine-synthesizing enzymes,
      resulting in changes in intracellular catecholamine levels available for
      consequent neurohormonal activities.

PMID- 9166716
TI  - Molecular cloning of a lobster G alpha(q) protein expressed in neurons of
      olfactory organ and brain.
AB  - We have isolated from an American lobster (Homarus americanus) olfactory organ
      cDNA library a clone, hG alpha(q), with >80% identity to mammalian and arthropod
      G alpha(q) sequences. In brain and olfactory organ, hG alpha(q) mRNA was
      expressed predominantly in neurons, including virtually all the neuronal cell
      body clusters of the brain. G alpha(q) protein was also expressed broadly,
      appearing on western blots as a single band of 46 kDa in brain, eyestalk,
      pereiopod, dactyl, tail muscle, olfactory organ, and aesthetasc hairs. These
      results suggest that hG alpha(q) plays a role in a wide variety of signal
      transduction events. Its presence in the olfactory aesthetasc hairs, which are
      almost pure preparations of the outer dendrites of the olfactory receptor
      neurons, the expression of a single hG alpha(q) mRNA species (6 kb) in the
      olfactory organ, and the localization of hG alpha(q) mRNA predominantly in the
      olfactory receptor neurons of the olfactory organ strongly suggest that one
      function of hG alpha(q) is to mediate olfactory transduction.

PMID- 9166717
TI  - Identification of a strand-specific Egr response element binding complex enriched
      in rat brain.
AB  - Multiple members of the Egr family of transcription regulatory factors are
      rapidly induced in response to neuronal stimulation and share a common double
      stranded DNA binding consensus sequence, referred to as the Egr response element.
      Recent studies have identified transcription regulatory factors that bind
      preferentially to short segments of single-stranded DNA, rather than the
      conventional double-stranded versions of regulatory elements. Accordingly, in the
      present study, we have investigated whether the Egr response element may also be
      regulated by trans factors that bind to single-stranded versions of this cis
      element. Using gel-shift studies, we have identified a protein complex that binds
      selectively to the G-rich strand of the Egr response element. In competition
      studies, an RNA oligonucleotide containing the corresponding G-rich sequence is
      approximately 25-fold less potent than its DNA counterpart. This DNA binding
      complex, referred to as GS1, is present in several regions of the rat brain with
      highest levels in cerebellum; negligible binding activity was detected in
      multiple peripheral tissues surveyed. UV cross-linking studies revealed two major
      protein bands with estimated molecular masses of 36 and 30 kDa. The highly
      restricted tissue distribution of this complex and its sequence-specific binding
      properties indicate that GS1 may be involved in regulating transcription directed
      by the Egr response element in brain.

PMID- 9166718
TI  - Differential expression of multiple somatostatin receptors in the rat cerebellum
      during development.
AB  - The present study describes the expression pattern of somatostatin receptor genes
      during the development of rat cerebellum. Characterization of somatostatin
      receptors was carried out by binding studies using receptor subtype-selective
      ligands in the germinative epithelium and granule cell layer of the cerebellum
      from postnatal day 4 (P4) to P21 and in granule cell cultures. Quantitative
      reverse transcription-PCR carried out for the five receptor subtype mRNAs in
      cerebellar extracts showed that sst1 mRNAs are predominant at the end of
      gestation. A transient high expression of the sst2 gene was observed from P7 to
      P14. In parallel, high levels of binding sites sensitive to sst2 ligands were
      detected in the granule cell germinative epithelium and in granule cell cultures.
      sst3 mRNAs rapidly increased from P14 and became the predominant form at P21, but
      respective binding sites were not detected. Whereas sst4 mRNA levels were
      generally low, those of sst5 were nearly undetectable. Reverse transcription-PCR
      carried out in granule cell cultures revealed the relative abundance of sst mRNAs
      as follows: sst2 > sst1 > sst3 = sst4. sst5 mRNA was undetectable. The results
      show the expression of four somatostatin receptor genes, but only three receptors
      (sst1, sst4, and mainly sst2) were detected as binding sites during cerebellar
      development.

PMID- 9166719
TI  - Distinct patterns of expression and physiological effects of sst1 and sst2
      receptor subtypes in mouse hypothalamic neurons and astrocytes in culture.
AB  - Somatostatin (SRIF) receptor subtypes (sst) were characterized in hypothalamic
      neurons and astrocytes by quantitative reverse transcription-polymerase chain
      reaction and radioreceptor assays using [125I-Tyr0,D-Trp8]SRIF-14 as a ligand in
      ionic conditions discriminating between SRIF-1 (sst2, -3, and -5 receptors) and
      SRIF-2 (sst1 and -4 receptors) binding sites. In neurons, sstl mRNA levels were
      twofold higher than those of sst2, and sst3-5 expression was only minor.
      Astrocytes expressed 10-fold less sst mRNAs than neurons, which corresponded
      mostly (80%) to sst2. SRIF-1 binding site radioautography indicated that 10% of
      hypothalamic neurons were labelled on both cell bodies and neuritic processes, as
      were 35% of astrocytes. On neuronal and glial membranes, SRIF-14 and octreotide,
      an sst2/sst3/sst5-selective analogue, completely displaced SRIF-1 binding,
      whereas des-AA(1,2,5)[D-Trp8,IAmp9]SRIF (CH-275), an sst1-selective analogue, was
      ineffective. Using SRIF-2 conditions, only SRIF-14 and CH-275 displaced the
      binding on neurons. No SRIF-2 binding was observed on glia. SRIF-14 and
      octreotide inhibited forskolin-stimulated adenylyl cyclase activity in neurons
      and glia, whereas CH-275 was effective in neurons only. In patch-clamp
      experiments, SRIF-14 modulated the glutamate sensitivity of hypothalamic neurons
      with either synergistic or antagonistic effects; CH-275 was only stimulatory and
      octreotide inhibitory. It is concluded that hypothalamic neurons express
      primarily sst1 and sst2, sst2 predominates in astrocytes, and both receptors
      induce distinct biological effects.

PMID- 9166721
TI  - Overexpression of adhesion molecule L1 in NG108-15 neuroblastoma X glioma hybrid
      cells enhances dibutyryl cyclic AMP-induced neurite outgrowth and functional
      synapse formation with myotubes.
AB  - The role of adhesion molecule L1 in synapse formation was examined by transient
      transfection of L1 cDNA in neuroblastoma x glioma hybrid NG108-15 cells. L1
      overexpression was found in approximately 50% of the transfected NG108-15 cell
      population. Neurite outgrowth induced by 0.25 mM dibutyryl cyclic AMP (cAMP) was
      much greater in L1-transfected NG108-15 cells than that in nontransfected and
      mock-transfected cells. The proportion of cells with neurites and the number of
      neurites per cells were increased in L1-transfected cells after 2 days of
      dibutyryl cAMP treatment. The proportion of cells with branched neurites and the
      average length of neurites were higher at day 4. A significantly higher rate of
      synapse formation with myotubes was apparent in the late phase of coculture (days
      4-7) in L1-transfected cells than in control cells. The miniature end-plate
      potential frequency in myotubes was the same for the three types of NG108-15
      cells. These results show that overexpression of L1 in NG108-15 cells facilitates
      synaptic connections by enhancing branching and elongation of neurites induced
      with dibutyryl cAMP, rather than by increasing probability of acetylcholine
      release.

PMID- 9166720
TI  - Effects of transforming growth factor-beta and platelet-derived growth factor on
      oligodendrocyte precursors: insights gained from a neuronal cell line.
AB  - Conditioned medium derived from a rat central nervous system neuronal cell line
      B104 (B104 CM) was shown previously to contain uncharacterized potent mitogen(s)
      for oligodendrocyte/type-2 astrocyte (O-2A) progenitor cells. In this study, we
      demonstrated that B104 cells produce and secrete platelet-derived growth factor
      (PDGF)-AA homodimer, but not PDGF-B chain. B104 cells did not express other known
      potent mitogens for O-2A progenitor cells, including fibroblast growth factor-2
      and neurotrophin-3. Unexpectedly, B104 cells also expressed transcripts of
      transforming growth factor-beta1 (TGF-beta1) and -beta2 (TGF-beta2), which are
      known to regulate O-2A progenitor cell differentiation and proliferation, and
      secreted exclusively the 25-kDa active forms of TGF-beta1 and TGF-beta2.
      Neutralization of B104 CM with anti-PDGF-AA antibody decreased proliferation of O
      2A progenitor cells, whereas neutralization with anti-TGF-beta antibodies had no
      effect. The combination of PDGF and TGF-beta on proliferation was not equivalent
      to the effect of B104 CM, indicating the possibility of an unidentified growth
      factor. B104 CM maintained a high expression of PDGF-alpha receptor in
      oligodendrocytes. The observation that both a stimulatory factor (PDGF-AA) and a
      regulatory factor (TGF-beta) for O-2A progenitor cell proliferation and
      differentiation are produced from a single neuronal cell line emphasizes the
      potential critical interaction between neurons and O-2A progenitor cells in
      myelination and possibly in remyelination.

PMID- 9166722
TI  - Depolarization and activation of dihydropyridine-sensitive Ca2+ channels
      stimulate inositol phosphate accumulation in photoreceptor-enriched chick retinal
      cell cultures.
AB  - Elevated concentrations of extracellular K+ increased inositol phosphate
      accumulation in primary cultures of chick retinal photoreceptors and multipolar
      neurons. K+-evoked stimulation of inositol phosphate accumulation was greater in
      photoreceptor-enriched cell cultures than in cultures where multipolar neurons
      were the predominant cell type. Destroying multipolar neurons, but not
      photoreceptors, with kainic acid and N-methyl-D-aspartate did not reduce the K+
      evoked stimulation of inositol phosphate accumulation. Both of these observations
      indicate that the observed effects occur in photoreceptor cells. The K+-evoked
      stimulation of inositol phosphate accumulation was blocked by omitting Ca2+ from
      the incubation medium or by adding the dihydropyridine-sensitive Ca2+-channel
      antagonists, nitrendipine and nifedipine. Bay K 8644, a dihydropyridine agonist,
      stimulated inositol phosphate accumulation and enhanced the effect of K+. omega
      Conotoxin GVIA, an inhibitor of N-type Ca2+ channels, had no significant effect
      on K+-stimulated inositol phosphate accumulation. Pretreatment with pertussis
      toxin neither blocked K+-evoked inositol phosphate accumulation nor altered the
      inhibitory effect of nifedipine. K+-evoked inositol phosphate accumulation
      appears to reflect activation of phosphatidylinositol-specific phospholipase C,
      as it is inhibited by U-73122. These results indicate that Ca2+ influx through
      voltage-gated, dihydropyridine-sensitive channels activates phospholipase C in
      photoreceptor inner segments and/or synaptic terminals.

PMID- 9166723
TI  - Regulation of corticotropin-releasing factor receptor function in human Y-79
      retinoblastoma cells: rapid and reversible homologous desensitization but
      prolonged recovery.
AB  - Homologous receptor desensitization is an important regulatory response to
      continuous activation by agonist that involves the uncoupling of a receptor from
      its G protein. When human retinoblastoma Y-79 cells expressing corticotropin
      releasing factor (CRF) receptors were preincubated with CRF for 10 min-4 h, a
      time-dependent reduction in both the peak and sensitivity of CRF-stimulated
      intracellular cyclic AMP (cAMP) accumulation developed with a t1/2 of 38 min and
      an EC50 of 6-7 nM CRF. CRF receptor desensitization was slowly reversible after a
      4-h CRF preincubation with a t1/2 of 13 h and a full restoration of cAMP
      responsiveness to CRF at 24 h following the removal of 10 nM CRF. Because the
      ability of vasoactive intestinal peptide, forskolin, or (-)-isoproterenol to
      stimulate cAMP accumulation was not diminished in Y-79 cells desensitized with 10
      nM CRF, the observed desensitization was considered to be a specific homologous
      action of CRF. CRF receptor desensitization was markedly attenuated by CRF
      receptor antagonists, which alone did not produce any appreciable reduction in
      CRF-stimulated cAMP accumulation. Although recent reports have demonstrated a
      rapid decline in steady-state levels of CRF receptor type 1 (CRF-R1) mRNA in
      anterior pituitary cells during several hours of exposure to CRF, there was no
      observed reduction in CRF-R1 mRNA levels when Y-79 cells were preincubated with
      10 nM CRF for 10 min-24 h despite a rapid time- and concentration-dependent loss
      of CRF receptors from the retinoblastoma cell surface.

PMID- 9166724
TI  - Comparison of type 2 inositol 1,4,5-trisphosphate receptor distribution and
      subcellular Ca2+ release sites that support Ca2+ waves in cultured astrocytes.
AB  - We have examined the mechanisms that underlie Ca2+ wave propagation in cultured
      cortical astrocytes. Norepinephrine evoked Ca2+ waves in astrocytes that began at
      discrete initiation loci and propagated throughout the cell by regenerative
      amplification at a number of cellular sites, as shown by very high Ca2+ release
      rates at these regions. We have hypothesized previously that domains displaying
      elevated Ca2+ release kinetics in astrocytes may correspond to sites of high
      inositol 1,4,5-trisphosphate receptor (InsP3R) density. To examine this
      possibility, we compared the distribution pattern of endoplasmic reticulum (ER)
      and InsP3Rs with Ca2+ release kinetics in subcellular regions during propagation
      of norepinephrine-evoked waves. 3,3'-Dihexyloxacarbocyanine iodide staining
      revealed that the ER in astrocytes exists as a meshwork of membranes extending
      throughout the cells, including fine processes. A specific antibody directed
      against type 2 InsP3Rs (InsP3R2) detected a 260-kDa band in western blotting of
      astrocyte membranes. Immunocytochemistry using this antibody stained the entire
      ER system in a punctate, variegated manner. When Ca2+ responses and InsP3R2
      immunofluorescence were compared in the same cell, domains of elevated Ca2+
      response kinetics (high amplitude and rapid rate of rise) showed significant
      positive correlation with high local intensity of InsP3R2 staining. It appears,
      therefore, that specializations in the ER responsible for discrete local Ca2+
      release sites that support regenerative wave propagation include increased levels
      of InsP3R2 expression.

PMID- 9166725
TI  - Characterization of CPP32-like protease activity following apoptotic challenge in
      SH-SY5Y neuroblastoma cells.
AB  - We characterized the activation of interleukin-1beta-converting enzyme (ICE)-like
      proteases (caspases) in human neuroblastoma cells (SH-SY5Y) following challenge
      with staurosporine, an established agent known to induce apoptosis. Time course
      analyses of lactate dehydrogenase release detected a significant increase in cell
      death as early as 6 h that continued at least until 24 h following staurosporine
      treatment. Western blot analyses using anti-poly(ADP-ribose) polymerase (anti
      PARP) and anti-CPP32 antibodies revealed proteolytic processing of CPP32 (an ICE
      homologue) as well as fragmentation of PARP as early as 3 h following
      staurosporine challenge. Furthermore, the hydrolysis of the CPP32 substrate
      acetyl-DEVD-7-amido-4-methylcoumarin was detected as early as 3 h and became
      maximal at 6 h after staurosporine challenge, suggesting a delayed and sustained
      period of CPP32-like activation. In addition, we used the first
      immunohistochemical examination of CPP32 and PARP in cells following an apoptotic
      challenge. The localization of CPP32 in untreated SH-SY5Y cells was exclusively
      restricted to the cytoplasm. Following staurosporine challenge there was a
      condensing of CPP32 immunofluorescence from the cytoplasm to a region adjacent to
      the plasma membrane. In contrast, PARP immunofluorescence was evenly distributed
      in the nucleus in untreated SH-SY5Y cells and on staurosporine challenge was
      found to be associated with condensed chromatin. It is important that a pan ICE
      inhibitor [carbobenzoxy-Asp-CH2OC(O)-2,6-dichlorobenzene] was able to attenuate
      lactate dehydrogenase release and PARP and CPP32 cleavage and altered
      immunohistochemical staining patterns for PARP and CPP32 following staurosporine
      challenge.

PMID- 9166726
TI  - Select alterations in protein kinases and phosphatases during apoptosis of
      differentiated PC12 cells.
AB  - The involvement of cell cycle-regulatory proteins in apoptosis of neuronally
      differentiated PC12 cells induced by the removal of nerve growth factor and serum
      was examined. Three major findings are presented. (1) Cdc2 kinase protein levels
      increased fivefold in apoptotic PC12 cells by day 3 of serum and nerve growth
      factor deprivation. Histone H1 kinase activity was increased significantly in
      p13(suc1) precipitates of apoptotic PC12 cells, which was due to increased
      activation and/or expression of cdc2 kinase. (2) The protein levels of cyclin
      dependent kinase 4, cyclin D, and proliferating cell nuclear antigen that are
      normally expressed in the cell cycle were increased during neuronal PC12 cell
      apoptosis. (3) The levels of the catalytic subunit, but not the regulatory
      subunit of the calcium/calmodulin-dependent protein phosphatase 2B, decreased
      significantly concomitant with a significant decrease in protein phosphatase 2B
      activity early in the apoptotic process. Protein phosphatase 2A activity
      decreased slightly but significantly after 3 days of serum and nerve growth
      factor deprivation, and no alterations in protein phosphatase 1 were observed
      during the apoptotic process. These data demonstrate that certain cell cycle
      regulatory proteins are inappropriately expressed and that alterations in
      specific phosphorylation events, as indicated by the increase in histone H1
      kinase activity and the decrease in protein phosphatase 2B activity, are most
      likely occurring during apoptosis of PC12 cells. These observations support the
      hypothesis that apoptosis may be due in part to a nondividing cell's
      uncoordinated attempt to reenter and progress through the cell cycle.

PMID- 9166727
TI  - Ganglioside GM1 enhances induction by nerve growth factor of a putative dimer of
      TrkA.
AB  - GM1 enhances nerve growth factor (NGF)-stimulated neuritogenesis and prevents
      apoptotic death of PC12 cells; both may be due to enhancement of TrkA
      dimerization. In this study, we examined the effect of GM1 on NGF-induced TrkA
      dimerization in Trk-PC12 (6-24) cells. NGF increased tyrosine phosphorylation of
      the 140-kDa protein (TrkA monomer), and preincubation with GM1 potentiated this
      effect. Adding the protein cross-linker bis(sulfosuccinimidyl) suberate with NGF
      resulted in the appearance of two major bands (220 and 330 kDa) when probed with
      antibodies against TrkA or phosphotyrosine, and GM1 also enhanced this effect. We
      interpret the 330-kDa band as being a homodimer of TrkA. The identity of the 220
      kDa band is still not certain but may consist of a posttranslationally modified
      form of TrkA. Our results suggest that GM1 is augmenting the effects of NGF on
      PC12 cells by enhancing the dimerization and activation of the TrkA receptor.

PMID- 9166728
TI  - Cholecystokinin-induced desensitization, receptor phosphorylation, and
      internalization in the CHP212 neuroblastoma cell line.
AB  - Agonist stimulation of cells often results in desensitization of the response, to
      protect the cell from overstimulation. We have previously shown that the type A
      cholecystokinin (CCK) receptor on the pancreatic acinar cell and on the model CHO
      CCKR cell line undergoes desensitization in response to CCK, with receptor
      phosphorylation and internalization playing key roles. Although these mechanisms
      contribute in a cell-specific manner, no analogous information exists for the CCK
      receptor expressed on neuronal cells, where in vivo data demonstrate a
      particularly sensitive response to CCK. The present study was designed to explore
      CCK receptor desensitization in the CHP212 neuroblastoma cell line, focusing on
      inositol 1,4,5-trisphosphate (IP3) responses to CCK and on recognized molecular
      and cellular mechanisms of desensitization. CCK promptly stimulated IP3 responses
      in these cells, with hormonal responsiveness rapidly and completely desensitized.
      Both receptor phosphorylation and internalization were observed to occur, with
      the former occurring most rapidly and likely being responsible for the earliest
      desensitization observed. Although the time course of receptor phosphorylation
      and dephosphorylation, and the groups of kinases involved in the neuroblastoma
      cell line, were most similar to those in the pancreatic cell, the movement of the
      agonist-bound receptor in these cells was quite different from that in the
      pancreatic cell and most similar to that in the CHO-CCKR cell line. This hybrid
      response supports the cell-specific nature of CCK receptor regulation and
      provides an important system to explore the molecular determinants of these
      processes.

PMID- 9166729
TI  - Chronic exposure to kappa-opioids enhances the susceptibility of immortalized
      neurons (F-11kappa 7) to apoptosis-inducing drugs by a mechanism that may involve
      ceramide.
AB  - Chronic exposure of embryonic brain to opioids leads to microcephaly and
      developmental abnormalities. An immortalized mouse neuroblastoma x dorsal root
      ganglion hybrid cell line stably transfected to overexpress kappa-opioid
      receptors (F-11kappa7) showed complete loss of kappa-receptor binding to
      [3H]U69,593 after exposure to the kappa-agonist U69,593 for 24 h. U69,593 had no
      measurable effect on cell viability as determined by either cell viability or DNA
      fragmentation assays. However, when cell death (apoptosis) was induced by either
      staurosporine or the phosphatidylinositol 3-kinase inhibitors wortmannin and
      LY294002, cells pretreated with U69,593 for 24 h showed increased apoptosis
      compared with untreated cells. Thus, staurosporine (50 nM), wortmannin (4
      microM), and LY294002 (30 microM) treatment for 24 h induced a 50% loss of cell
      viability and DNA fragmentation in 24 h. U69,593 pretreatment produced the same
      killing at lower concentrations, namely, 20 nM staurosporine, 2 microM
      wortmannin, and 14 microM LY294002, respectively. The effects of U69,593 were
      time-, dose-, and naloxone-reversible, suggesting that they are receptor
      mediated. However, coaddition of U69,593 at the same time as staurosporine,
      wortmannin, or LY294002 did not enhance apoptosis. All three drugs that induced
      apoptosis were found to increase the level of ceramide, and pretreatment with
      U69,593 further increased the rate of formation of ceramide, a lipid that induces
      apoptosis in cells. We propose that chronic exposure to kappa-receptor agonists
      promotes increased vulnerability of neurons to apoptosis.

PMID- 9166730
TI  - Protection of flupirtine on beta-amyloid-induced apoptosis in neuronal cells in
      vitro: prevention of amyloid-induced glutathione depletion.
AB  - Effective drugs are not available to protect against beta-amyloid peptide (A
      beta)-induced neurotoxicity. Cortical neurons from rat embryos were treated with
      the toxic fragment A beta25-35 at 1 microM in the presence or absence of
      flupirtine, a triaminopyridine, successfully applied clinically as a nonopiate
      analgesic drug. Five days later 1 microM A beta25-35 caused reduction of cell
      viability to 31.1%. Preincubation of cells with flupirtine (1 or 5 microg/ml)
      resulted in a significant increase of the percentage of viable cells (74.6 and
      65.4%, respectively). During incubation with A beta25-35 the neurons undergo
      apoptosis as determined by appearance of the characteristic stepladder-like DNA
      fragmentation pattern and by the TUNEL technique. A beta25-35-induced DNA
      fragmentation could be abolished by preincubation of the cells with 1 microg/ml
      flupirtine. Incubation with A beta25-35 reduces the intraneuronal level of GSH
      from 21.4 to 7.4 nmol/10(6) cells. This depletion could be partially prevented by
      preincubation of the cells with flupirtine. Thus, flupirtine may be adequate for
      the treatment of the neuronal loss in Alzheimer's disease (where A beta
      accumulates in senile plaques) and probably other neurological diseases such as
      amyotrophic lateral sclerosis.

PMID- 9166731
TI  - Cerebral astrocytes transport ascorbic acid and dehydroascorbic acid through
      distinct mechanisms regulated by cyclic AMP.
AB  - Cerebral ischemia and trauma lead to rapid increases in cerebral concentrations
      of cyclic AMP and dehydroascorbic acid (DHAA; oxidized vitamin C), depletion of
      intracellular ascorbic acid (AA; reduced vitamin C), and formation of reactive
      astrocytes. We investigated astrocytic transport of AA and DHAA and the effects
      of cyclic AMP on these transport systems. Primary cultures of astrocytes
      accumulated millimolar concentrations of intracellular AA when incubated in
      medium containing either AA or DHAA. AA uptake was Na+-dependent and inhibited by
      4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), whereas DHAA uptake was
      Na+-independent and DIDS-insensitive. DHAA uptake was inhibited by cytochalasin
      B, D-glucose, and glucose analogues specific for facilitative hexose
      transporters. Once inside the cells, DHAA was reduced to AA. DHAA reduction
      greatly decreased astrocytic glutathione concentration. However, experiments with
      astrocytes that had been previously depleted of glutathione showed that DHAA
      reduction does not require physiological concentrations of glutathione. Astrocyte
      cultures were treated with a permeant analogue of cyclic AMP or forskolin, an
      activator of adenylyl cyclase, to induce cellular differentiation and thus
      provide in vitro models of reactive astrocytes. Cyclic AMP stimulated uptake of
      AA, DHAA, and 2-deoxyglucose. The effects of cyclic AMP required at least 12 h
      and were inhibited by cycloheximide, consistent with a requirement for de novo
      protein synthesis. Uptake and reduction of DHAA by astrocytes may be a recycling
      pathway that contributes to brain AA homeostasis. These results also indicate a
      role for cyclic AMP in accelerating the clearance and detoxification of DHAA in
      the brain.

PMID- 9166732
TI  - beta-Adrenergic stimulation promotes homocysteic acid release from astrocyte
      cultures: evidence for a role of astrocytes in the modulation of synaptic
      transmission.
AB  - The sulfur-containing amino acid homocysteic acid (HCA) is present in and
      released from nervous tissue, exerting excitatory effects on neurons by
      predominantly activating NMDA receptors. It is interesting that HCA appears to be
      exclusively localized in glial cells, not in neurons. This profile of glial
      localization and excitatory action on neurons has led to the hypothesis that HCA
      could participate in intercellular communication in the brain as a
      "gliotransmitter." To test this hypothesis further, we searched for specific,
      receptor-mediated stimuli that could induce release of HCA from cultured
      astrocytes. For this reason we tested the effect of noradrenaline and vasoactive
      intestinal peptide, two transmitters known to interact with specific receptors on
      astrocytes, on the release of HCA from these cells. Noradrenaline and the beta
      adrenergic agonist isoproterenol induced an efflux of HCA from astrocyte
      cultures. Further stressing the beta-adrenergic mediation of this effect is the
      blockade by atenolol of the HCA release evoked by isoproterenol. The stimulation
      of HCA release from astrocytes was not observed with the alpha-noradrenergic
      agonist methoxamine and with vasoactive intestinal peptide. These results taken
      together further strengthen the role of HCA as a gliotransmitter. Its efflux from
      glia could be controlled by noradrenaline, activating beta-adrenergic receptors
      on astrocytes. The present study provides the first evidence for an influence of
      beta-adrenergic receptor activation on the release of an excitatory amino acid
      from astrocytes and further supports the notion that glial-neuronal interactions
      play a role in synaptic transmission.

PMID- 9166733
TI  - A constitutively internalizing and recycling mutant of the mu-opioid receptor.
AB  - Internalization and recycling of G protein-coupled receptors (GPCRs), such as the
      mu-opioid receptor, largely depend on agonist stimulation, whereas certain other
      receptor types recycle constitutively, e.g., the transferrin receptor. To
      investigate structural domains involved in mu-opioid receptor internalization, we
      constructed two truncation mutants bracketing a Ser/Thr-rich domain
      (354ThrSerSerThrIleGluGlnGlnAsn362) unique to the C-terminus of the mu-opioid
      receptor (mutants Trunc354 and Trunc363). Ligand binding did not differ
      substantially, and G protein coupling was slightly lower for these mu-receptor
      constructs, in particular for Trunc363. To permit localization of the receptor by
      immunocytochemistry, an epitope tag was added to the N-terminus of the wild-type
      and mutant receptors. Both the wild-type mu-opioid receptor and Trunc363 resided
      largely at the plasma membrane and internalized into vesicles upon stimulation
      with the agonist [D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin. Internalization occurred
      into vesicles that contain transferrin receptors, as shown previously, as well as
      clathrin, but not caveolin. In contrast, even without any agonist present,
      Trunc354 colocalized in intracellular vesicles with clathrin and transferrin
      receptors, but not caveolin. On blocking internalization by hyperosmolar sucrose
      or acid treatment, Trunc354 translocated to the plasma membrane, indicating that
      the mutant internalized into clathrin-coated vesicles and recycled
      constitutively. Despite agonist-independent internalization of Trunc354, basal G
      protein coupling was not elevated, suggesting distinct mechanisms for coupling
      and internalization. Furthermore, a portion of the C-terminus, particularly the
      Ser/Thr domain, appears to suppress mu-receptor internalization, which can be
      overcome by agonist stimulation. These results demonstrate that a mutant GPCR can
      be constructed such that internalization, normally an agonist-dependent process,
      can occur spontaneously without concomitant G protein activation.

PMID- 9166734
TI  - Responses of Bergmann glia and granule neurons in situ to N-methyl-D-aspartate,
      norepinephrine, and high potassium.
AB  - To gain insight into neuronal-glial signaling in brain, cerebellar Bergmann glia
      and granule neurons were studied in acutely isolated slices with the aid of laser
      scanning confocal microscopy. Both Bergmann glia and granule neurons responded to
      N-methyl-D-aspartate (NMDA) with a rise in [Ca2+]i. However, the glial NMDA
      response was frequently inhibited by tetrodotoxin, suggesting that the response
      depended on neuronal action potentials, rather than on direct activation of NMDA
      receptors on the Bergmann glia. Further experiments demonstrated that the NMDA
      response in Bergmann glia was not inhibited by a combination of non-NMDA
      glutamate receptor blockers 6-cyano-7-nitroquinoxaline-2,3-dione and alpha-methyl
      4-carboxyphenylglycine. Bergmann glia also responded to norepinephrine and high
      K+, and the responses were not inhibited by tetrodotoxin. The glial
      norepinephrine response was blocked by phentolamine but not by the removal of
      external Ca2+, indicating a direct activation of alpha1-adrenergic receptors that
      mediated release of Ca2+ from intracellular stores. The KCl-induced response in
      both neurons and glia was dependent on external Ca2+ and was blocked by verapamil
      or nifedipine. In summary, our data indicate that Bergmann glia in situ recognize
      a signal(s) released from neurons during neuronal activity.

PMID- 9166735
TI  - Neurosteroids modulate nicotinic receptor function in mouse striatal and thalamic
      synaptosomes.
AB  - Progesterone and its A-ring reduced metabolites are allosteric activators of
      GABA(A) receptors. The studies reported here examined the effects of these
      steroids on brain nicotinic receptors using an 86Rb+ efflux assay that likely
      measures the function of alpha4beta2-type nicotinic receptors and [3H]dopamine
      release, which may be modulated by an alpha3-containing nicotinic receptor. Both
      of the A-ring reduced metabolites of progesterone were noncompetitive inhibitors
      of both assays, whereas progesterone inhibited only the 86Rb+ efflux assay. The
      86Rb+ efflux assay was slightly more sensitive than was the dopamine release
      assay to steroid inhibition. Inhibition developed slowly for both assays (t1/2 =
      0.4 min) and was reversed even more slowly (t1/2 = 10-15 min). Steroid addition
      did not alter either the rate of association of [3H]nicotine binding to brain
      membranes, nor was equilibrium binding changed. These findings argue that
      neurosteroids are allosteric inhibitors of brain nicotinic receptors.

PMID- 9166736
TI  - Stable expression of recombinant AMPA receptor subunits: binding affinities and
      effects of allosteric modulators.
AB  - Homomeric AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type
      glutamate receptors (GluRs) were stably expressed in kidney cells from cDNAs
      encoding GluR1 flop, GluR2 flip, GluR2 flop, and GluR3 flop subunits. The
      recombinant receptors were of the expected size and showed functional properties
      in whole-cell recording as previously reported. [3H]AMPA binding to all subunits
      was increased to a similar extent by the chaotropic ion thiocyanate (SCN-).
      Significant differences were found in the Scatchard plots, however, which were
      linear and of high affinity for GluR1 and -3 receptors (K(D) values of 33 and 52
      nM, respectively) but showed curvature for GluR2 receptors, indicating the
      presence of two components with distinct affinities. As with brain AMPA
      receptors, solubilization of GluR2 receptors reduced the number of lower-affinity
      sites and correspondingly increased the number of higher-affinity sites. The
      sulfhydryl reagent p-chloromercuriphenylsulfonic acid, which increases binding to
      brain receptors, produced only minor changes except in the case of GluR2 flip.
      These results indicate that GluR2, among the subunits examined here, most closely
      resembles the native AMPA receptors in brain membranes. [3H]AMPA binding was
      inhibited in a noncompetitive manner by two drugs that change the desensitization
      kinetics of the AMPA receptor. In agreement with physiological observations, the
      apparent affinity of cyclothiazide for GluR2 flip (EC50 = 7 microM) was higher
      than that for receptors made of flop subunits (49-130 microM). In contrast, BDP
      37, a member of the benzamide family of drugs, exhibited a lower potency for
      GluR2 flip (58 microM) than for any of the flop isoforms (18-40 microM). These
      results predict that the action of centrally active AMPA-receptor modulators
      varies across brain regions depending on their flip/flop composition.

PMID- 9166737
TI  - Monoamine transporter gene expression in the central nervous system in diabetes
      mellitus.
AB  - Diabetic animals exhibit altered neurotransmission in brain monoaminergic
      systems. By means of in situ hybridization, we have investigated the expression
      of dopamine, noradrenaline, and serotonin transporter (DA-T, NA-T, and 5-HT-T,
      respectively) mRNAs in the brains of alloxan- and streptozotocin-diabetic rats.
      The expression of DA-T mRNA is decreased in 1- (-11%) and 4- (-17%) week alloxan
      diabetic and 4- (-9%) and 8- (-20%) week streptozotocin-diabetic rats in the
      ventral medial bundle. The expression of NA-T mRNA is decreased in the locus
      coeruleus of 8- (-26%) week streptozotocin-diabetic rats, in the noradrenergic A1
      cell group of 4- (-27%) week alloxan- and 8- (-25%) week streptozotocin-diabetic
      rats, and in the noradrenergic A2 cell group of 1- (-21%) and 4- (-28%) week
      alloxan-diabetic and 4- (-27%) and 8- (-25%) week streptozotocin-diabetic
      animals. The expression of 5-HT-T mRNA in the dorsal raphe nucleus is increased
      in 1- (+14%) and 4- (+44%) week alloxan- and 4- (+28%) and 8- (+44%) week
      streptozotocin-diabetic rats. The expression of each of the three monoamine
      transporter genes may be differentially regulated in diabetes and dependent on
      the duration of diabetes. Altered monoamine transporter gene expression may
      possibly contribute to the observed dysfunctions in brain monoamine transmission
      in chronic diabetes.

PMID- 9166738
TI  - Cocaine induces apoptosis in cortical neurons of fetal mice.
AB  - Exposure of fetal mouse brain cocultures to cocaine results selectively in the
      loss of neurites followed by neuronal death. By using enriched neuronal cultures,
      we here demonstrate that disappearance of neurons, when cultured with cocaine, is
      caused by apoptosis, based on (1) characteristic morphology of apoptotic nuclei
      at the level of neurons but not of glial cells by optic microscopy, and on total
      cell pellets by electron microscopy; (2) fragmentation of total DNA with a
      typical "ladder" pattern on agarose gels; (3) extensive in situ DNA fragmentation
      labeling (TUNEL method); and (4) prevention of cell loss by cycloheximide. The
      major metabolites of cocaine have no detectable effects on neurons, indicating
      that apoptosis is due to cocaine itself. Inappropriate neuronal apoptosis in
      cocaine-exposed fetal brain could perturb the neurodevelopmental program and
      contribute to the quantitative neuronal defects that are too frequently reported
      in the offspring of cocaine-abusing pregnant women.

PMID- 9166739
TI  - Oxidatively induced structural alteration of glutamine synthetase assessed by
      analysis of spin label incorporation kinetics: relevance to Alzheimer's disease.
AB  - The activity of the astrocytic enzyme glutamine synthetase (GS) is decreased in
      the Alzheimer's disease brain, which may have relevance to mechanisms of chronic
      excitotoxicity. The molecular perturbation(s) that results in GS inactivation is
      not known, although oxidative lesioning of the enzyme is one likely cause. To
      assess structural perturbation induced in GS by metal-catalyzed oxidation, a
      series of spin-labeling studies were undertaken. Ovine GS was oxidized by
      exposure to iron/hydrogen peroxide and subsequently labeled with the thiol
      specific nitroxide probe MTS [(1-oxyl-2,2,5,5-tetramethyl-pyrroline-3
      methyl)methanethiosulfonate]. The reaction of MTS with cysteine residues within
      GS was monitored in real time by electron paramagnetic resonance spectrometry.
      Structural perturbation of GS, manifested as decreased thiol accessibility, was
      inferred from an apparent decrease in the rate constant for the second-order
      reaction of MTS with protein thiols. A subsequent spin-labeling study was
      undertaken to compare the structural integrity of GS purified and isolated from
      Alzheimer's disease-afflicted brain (AD-GS) with that of GS isolated from
      nondemented, age-matched control brain (C-GS). The rate constant for reaction of
      MTS with AD-GS was markedly decreased relative to that for the reaction of spin
      label with C-GS. The kinetic data were partially corroborated by spectroscopic
      data obtained from circular dichroism analysis of control and peroxide-treated
      ovine GS. In an adjunct experiment, the interaction of GS with a synthetic
      analogue of the Alzheimer's-associated beta-amyloid peptide, known to induce free
      radical oxidative stress, indicated strong interaction of the enzyme with the
      peptide as reflected by a decrease in the rate constant for MTS binding to
      reactive protein thiols.

PMID- 9166740
TI  - Time course changes in the dopaminergic nigrostriatal system following
      transection of the medial forebrain bundle: detection of oxidatively modified
      proteins in substantia nigra.
AB  - We studied the time course of oxidatively modified proteins in the nigrostriatal
      dopaminergic system following transection of the medial forebrain bundle by
      quantifying the number of carbonyl groups coupled to striatal and nigral protein
      homogenates, an index of metal-catalyzed oxidations. We found a striking effect
      of axotomy on the number of oxidatively modified proteins in the substantia nigra
      but not in the striatum within the first 5 days postlesion. This effect was
      correlated with the neurochemical activity of the dopaminergic and serotoninergic
      systems in the substantia nigra, which suggests a role of dopamine- and serotonin
      derived radical oxygen species in the oxidative stress detected in this brain
      area. We then searched for the type of cell death in the substantia nigra
      following axotomy. The fragmentation pattern obtained by agarose gel
      electrophoresis of DNA isolated from nigral tissue was indicative of cell death
      being entirely necrotic. In fact, no evidence of apoptosis was detected at any
      postlesion time as revealed by TdT-mediated dUTP-biotin nick end-labeling (TUNEL)
      staining. The course of necrotic cell death in the substantia nigra coincided
      with the maximal levels of oxidatively modified proteins in the substantia nigra,
      suggesting a link between oxidative stress and nerve cell death and also
      coinciding with the neurochemical activity of both dopaminergic and
      serotoninergic systems.

PMID- 9166741
TI  - 4-hydroxynonenal, a lipid peroxidation product, rapidly accumulates following
      traumatic spinal cord injury and inhibits glutamate uptake.
AB  - Traumatic injury to the spinal cord initiates a host of pathophysiological events
      that are secondary to the initial insult. One such event is the accumulation of
      free radicals that damage lipids, proteins, and nucleic acids. A major reactive
      product formed following lipid peroxidation is the aldehyde, 4-hydroxynonenal
      (HNE), which cross-links to side chain amino acids and inhibits the function of
      several key metabolic enzymes. In the present study, we used immunocytochemical
      and immunoblotting techniques to examine the accumulation of protein-bound HNE,
      and synaptosomal preparations to study the effects of spinal cord injury and HNE
      formation on glutamate uptake. Protein-bound HNE increased in content in the
      damaged spinal cord at early times following injury (1-24 h) and was found to
      accumulate in myelinated fibers distant to the site of injury. Immunoblots
      revealed that protein-bound HNE levels increased dramatically over the same
      postinjury interval. Glutamate uptake in synaptosomal preparations from injured
      spinal cords was decreased by 65% at 24 h following injury. Treatment of control
      spinal cord synaptosomes with HNE was found to decrease significantly, in a dose
      dependent fashion, glutamate uptake, an effect that was mimicked by inducers of
      lipid peroxidation. Taken together, these findings demonstrate that the lipid
      peroxidation product HNE rapidly accumulates in the spinal cord following injury
      and that a major consequence of HNE accumulation is a decrease in glutamate
      uptake, which may potentiate neuronal cell dysfunction and death through
      excitotoxic mechanisms.

PMID- 9166743
TI  - Chronic intermittent ethanol treatment in rats increases GABA(A) receptor alpha4
      subunit expression: possible relevance to alcohol dependence.
AB  - Chronic administration of ethanol to rats on an intermittent regimen, for 60
      repeated intoxicating doses and repeated withdrawal episodes, results in a long
      lasting kindling phenomenon. This involves an increasing severity of withdrawal,
      including a reduced threshold to seizures produced by the GABA(A) antagonist,
      pentylenetetrazol. We have shown previously that muscimol-evoked 36Cl- efflux and
      paired-pulse inhibition (involving GABA(A)-mediated recurrent inhibition) were
      decreased persistently in the CA1 region of hippocampal slices from chronic
      intermittent ethanol (CIE)-treated rats. We now report elevated levels of mRNA in
      forebrain for the alpha4 subunit of the GABA(A) receptor (GABAR), considered to
      be a constituent of pharmacologically and physiologically novel subtypes of
      GABARs. Using in situ hybridization with digoxigenin-labeled RNA probes, we show
      that at 2 days withdrawal, 60-dose CIE leads to a significant 30% increase in
      alpha4 subunit mRNA levels in the dentate gyrus, 46% increase in the CA3, and 26%
      increase in the CA1 regions. In contrast, there was no significant change in the
      mRNAs for the alpha5 subunit or glutamic acid decarboxylase 67 in the same
      regions. This study suggests that GABAR subunit-selective alterations occur after
      CIE treatment, possibly resulting in the alteration of the subunit composition of
      GABARs, with presumably altered physiological functions. This plasticity of
      GABARs may contribute to the increased withdrawal severity, reduced hippocampal
      inhibition, and increased seizure susceptibility of this animal model of human
      alcohol dependence.

PMID- 9166744
TI  - Koningic acid (a potent glyceraldehyde-3-phosphate dehydrogenase inhibitor)
      induced fragmentation and condensation of DNA in NG108-15 cells.
AB  - We examined nitric oxide (NO)-induced cell death in NG108-15 cells using NO
      donors. Both sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine
      caused lactate dehydrogenase (LDH) leakage from NG108-15 cells. NO is known to
      increase the amount of radioisotopic labeled glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) in the presence of [32P]NAD and to inhibit the enzyme
      activity. To clarify the relationship between the NO-induced inhibition of GAPDH
      activity and cell death, we studied the effect of koningic acid (KA), a potent
      selective inhibitor of GAPDH. Both SNP and KA elicited LDH leakage, chromosomal
      condensation, and fragmentation of nuclei in NG108-15 cells. Gel electrophoretic
      analysis of cellular DNA extracted from SNP- and KA-treated cells revealed the
      internucleosomal DNA fragmentation typical of apoptosis in these cultures. The
      results suggested that in NG108-15 cells, (a) the inhibition of GAPDH activity
      results in apoptosis and (b) SNP-induced cell death is partly due to the NO
      induced inhibition of GAPDH, perhaps by stimulating the binding of NAD to GAPDH.

PMID- 9166742
TI  - Inhibition of tyrosine aminotransferase by beta-N-oxalyl-L-alpha,beta
      diaminopropionic acid, the Lathyrus sativus neurotoxin.
AB  - Species differences in susceptibility are a unique feature associated with the
      neurotoxicity of beta-N-oxalyl-L-alpha,beta-diaminopropionic acid (L-ODAP), the
      Lathyrus sativus neurotoxin, and the excitotoxic mechanism proposed for its
      mechanism of toxicity does not account for this feature. The present study
      examines whether neurotoxicity of L-ODAP is the result of an interference in the
      metabolism of any amino acid and if it could form the basis to explain the
      species differences in susceptibility. Thus, Wistar rats and BALB/c (white) mice,
      which are normally resistant to L-ODAP, became susceptible to it following
      pretreatment with tyrosine (or phenylalanine), exhibiting typical neurotoxic
      symptoms. C57BL/6J (black) mice were, however, normally susceptible to L-ODAP
      without any pretreatment with tyrosine. Among the various enzymes associated with
      tyrosine metabolism examined, the activity of only tyrosine aminotransferase
      (TAT) was inhibited specifically by L-ODAP. The inhibition was noncompetitive
      with respect to tyrosine (Ki = 2.0 +/- 0.1 mM) and uncompetitive with respect to
      alpha-ketoglutarate (Ki = 8.4 +/- 1.5 mM). The inhibition of TAT was also
      reflected in a marked decrease in the rate of oxidation of tyrosine by liver
      slices, an increase in tyrosine levels of liver, and also a twofold increase in
      the dopa and dopamine contents of brain in L-ODAP-injected black mice. The dopa
      and dopamine contents in the brain of only L-ODAP-injected white mice did not
      show any change, whereas levels of these compounds were much higher in tyrosine
      pretreated animals. Also, the radioactivity associated with tyrosine, dopa, and
      dopamine arising from [14C]tyrosine was twofold higher in both liver and brain of
      L-ODAP-treated black mice. Thus, a transient increase in tyrosine levels
      following the inhibition of hepatic TAT by L-ODAP and its increased availability
      for the enhanced synthesis of dopa and dopamine and other likely metabolites
      (toxic?) resulting therefrom could be the mechanism of neurotoxicity and may even
      underlie the species differences in susceptibility to this neurotoxin.

PMID- 9166745
TI  - Protective effects of pyridoxal phosphate against glucose deprivation-induced
      damage in cultured hippocampal neurons.
AB  - When hippocampal cultures were deprived of glucose, massive release of lactate
      dehydrogenase (LDH), an indicator of neuronal death, occurred via NMDA receptor
      activation. Addition of pyridoxal phosphate (PLP; 1 and 10 microM) inhibited this
      LDH release in a concentration-dependent manner. Prior exposure to PLP evoked
      more potent inhibitory effects on LDH release compared with those treated at the
      onset of glucose deprivation. Furthermore, PLP inhibited the reduction of
      intracellular content of pyruvate induced by glucose deprivation, which was
      accompanied by the reversal of intracellular ATP depletion. A noteworthy
      elevation of extracellular glutamate in response to glucose deprivation was
      completely reversed by addition of PLP. Aminooxyacetic acid, a potent inhibitor
      of PLP-dependent enzymes, antagonized the effects of PLP on LDH release, pyruvate
      production, and ATP formation. These results suggest that PLP protects neurons
      from glucose deprivation-induced damage by enhancing the formation of energy
      yielding products and relieving extracellular load of glutamate. The observed
      phenomena further indicate that PLP might be used prophylactically against
      neuronal death induced by metabolic disorders.

PMID- 9166746
TI  - Inhibition of ischemia-induced fodrin breakdown by a novel phenylpyrimidine
      derivative NS-7: an implication for its neuroprotective action in rats with
      middle cerebral artery occlusion.
AB  - The effect of a novel neuroprotective compound, NS-7 [4-(4-fluorophenyl)-2-methyl
      6-(5-piperidinopentyloxy)pyrimidine hydrochloride], on ischemia-induced fodrin
      breakdown was examined both in vitro and in vivo. The fodrin breakdown was
      measured by western blot followed by a densitometric analysis. In slices of the
      rat cerebral cortex, a pronounced fodrin breakdown was observed under hypoxic and
      hypoglycemic conditions. The enhancement of fodrin breakdown was completely
      blocked by omission of extracellular Ca2+ and significantly inhibited by calpain
      inhibitors such as E-64 and calpain inhibitor-I, thereby suggesting that the
      fodrin breakdown induced by hypoxia/hypoglycemia is due to the activation of Ca2+
      stimulated neutral protease calpain. NS-7 (1-30 microM) produced a concentration
      dependent inhibition of hypoxia/hypoglycemia-induced fodrin breakdown. In rats
      with unilateral middle cerebral artery occlusion (MCAO), a pronounced fodrin
      breakdown was observed in the cerebral cortex and striatum, although the time
      course for the development of the fodrin breakdown was much slower in the
      cerebral cortex than in the striatum. NS-7 (0.5 mg/kg i.v.), when injected
      immediately after MCAO, suppressed not only the fodrin breakdown but also the
      infarction in the cerebral cortex. From these results it is suggested that
      inhibition of calpain activation is implicated in the neuroprotective action of
      NS-7.

PMID- 9166747
TI  - Functional role of amino-terminal serine16 and serine27 of G alphaZ in receptor
      and effector coupling.
AB  - The alpha subunit of Gz (alpha(z)) harbors two N-terminal serine residues (at
      positions 16 and 27) that serve as protein kinase C-mediated phosphorylation
      sites. The cognate residues in the alpha subunit of Gt1 provide binding surfaces
      for the beta1 subunit. We used three serine-to-alanine mutants of alpha(z) to
      investigate the functional importance of the two N-terminal serine residues. Wild
      type or mutant alpha(z) was transiently coexpressed with different receptors and
      adenylyl cyclase isozymes in human embryonic kidney 293 cells, and agonist
      dependent regulation of cyclic AMP accumulation was examined in a setting where
      all endogenous alpha subunits of G1 were inactivated by pertussis toxin.
      Replacement of one or both serine residues by alanine did not alter the ability
      of alpha(z) to interact with delta-opioid, dopamine D2, or adenosine A1
      receptors. Its capacity to inhibit endogenous and type VI adenylyl cyclases was
      also unaffected. Functional release of betagamma subunits from the mutant
      alpha(z) subunits was not impaired because they transduced betagamma-mediated
      stimulation of type II adenylyl cyclase. Constitutively active mutants of all
      four alpha(z) subunits were constructed by the introduction of a Q205L mutation.
      The activated mutants showed differential abilities to inhibit human
      choriogonadotropin-mediated cyclic AMP accumulation in luteinizing hormone
      receptor-transfected cells. Loss of both serine residues, but not either one
      alone, impaired the receptor-independent inhibition of adenylyl cyclase by the
      GTPase-deficient mutant. Thus, replacement of the amino-terminal serine residues
      of alpha(z) has no apparent effect on receptor-mediated responses, but these
      serine residues may be essential for ensuring transition of alpha(z) into the
      active conformation.

PMID- 9166748
TI  - Increased secretion of the amino-terminal fragment of amyloid precursor protein
      in brains of rats with a constitutive up-regulation of protein kinase C.
AB  - Protein kinase C (PKC) activation stimulates release of secreted amyloid
      precursor protein (APPs) in several cell lines. To ascertain the role of PKC in
      regulating APP metabolism in vivo, we used an animal model (methylazoxymethanol
      treated rats; MAM rats) in which PKC is permanently hyperactivated in selected
      brain areas, i.e., cortex and hippocampus. A significant decrease in membrane
      bound APP concentration was found in synaptosomes derived from cortex and
      hippocampus of MAM rats, where PKC is up-regulated, with a concomitant increase
      in APPs production in soluble fractions of the same brain areas. In contrast, in
      a brain area not affected by MAM treatment (i.e., cerebellum), APP secretion is
      similar in control and MAM rats, indicating that altered metabolism of APP is
      restricted to only those areas in which the PKC system is up-regulated. In
      addition, phorbol esters or H-7 modulate APPs release in hippocampal slices from
      both control and MAM rats, further supporting an in vivo role for this enzyme in
      regulating metabolism of mature APP.

PMID- 9166749
TI  - The globin fragment LVV-hemorphin-7 is an endogenous ligand for the AT4 receptor
      in the brain.
AB  - Angiotensin IV (Val-Tyr-Ile-His-Pro-Phe) has been reported to interact with
      specific high-affinity receptors to increase memory retrieval, enhance dopamine
      induced stereotypy behavior, and induce c-fos expression in several brain nuclei.
      We have isolated a decapeptide (Leu-Val-Val-Tyr-Pro-Trp-Thr-Gln-Arg-Phe) from
      sheep brain that binds with high affinity to the angiotensin IV receptor. The
      peptide was isolated using 125I-angiotensin IV binding to bovine adrenal
      membranes to assay receptor binding activity. This peptide is identical to the
      amino acid sequence 30-39 of sheep betaA- and betaB-globins and has previously
      been named LVV-hemorphin-7. Pharmacological studies demonstrated that LVV
      hemorphin-7 and angiotensin IV were equipotent in competing for 125I-angiotensin
      IV binding to sheep cerebellar membranes and displayed full cross-displacement.
      Using in vitro receptor autoradiography, 125I-LVV-hemorphin-7 binding to sheep
      brain sections was identical to 125I-angiotensin IV binding in its pattern of
      distribution and binding specificity. This study reveals the presence of a globin
      fragment in the sheep brain that exhibits a high affinity for, and displays an
      identical receptor distribution with, the angiotensin IV receptor. This globin
      fragment, LVV-hemorphin-7, may therefore represent an endogenous ligand for the
      angiotensin IV receptor in the CNS.

PMID- 9166750
TI  - Spatial learning activates neural cell adhesion molecule polysialylation in a
      corticohippocampal pathway within the medial temporal lobe.
AB  - Transient and time-dependent modulations of neural cell adhesion molecule (NCAM)
      polysialylation in the dentate gyrus of the rodent hippocampus are a feature of
      spatial and nonspatial forms of learning. In the hippocampal formation,
      polysialic acid immunoreactivity was localized to granule-like cells and their
      mossy fibre axons. We now demonstrate the latter to extend to the CA3 region
      where apparent recurrent and Schaffer collaterals were labelled. The axons of the
      CA1 pyramidal cell layer were immunopositive, as was the subiculum that they
      innervate. Layers I and III of the entorhinal cortex stained intensely for
      polysialic acid; however, these were not visible in the more lateral aspect of
      this region and were replaced by a single band of immunopositive neurons that
      extended to include the perirhinal and piriform cortices. After Morris water maze
      training, the number of polysialylated neurons within the entorhinal cortex
      exhibited a two- to threefold increase at the 10-12-h posttraining time with
      respect to that observed immediately after training. This increase was task
      specific, as no change was observed in freely swimming animals or those required
      to locate a visible platform. These results suggest the presence of a
      corticohippocampal pathway involved in the eventual consolidation of memory.

PMID- 9166751
TI  - Pretreatment of astrocytes with interferon-alpha/beta impairs interferon-gamma
      induction of nitric oxide synthase.
AB  - Excessive nitric oxide/peroxynitrite generation has been implicated in the
      pathogenesis of multiple sclerosis, and the demonstration of increased astrocytic
      nitric oxide synthase activity in the postmortem brain of multiple sclerosis
      patients supports this hypothesis. Exposure of astrocytes, in primary culture, to
      interferon-gamma results in stimulation of nitric oxide synthase activity and
      increased nitric oxide release. In contrast to interferon-gamma, interferon
      alpha/beta had a minimal effect on astrocytic nitric oxide formation.
      Furthermore, pretreatment of astrocytes with interferon-alpha/beta inhibited
      (approximately 65%) stimulation by interferon-gamma of nitric oxide synthase
      activity and nitric oxide release. Treatment with interferon-alpha/beta at a
      concentration as low as 10 U/ml caused inhibition of mitochondrial cytochrome c
      oxidase. Furthermore, the damage to cytochrome c oxidase was prevented by the
      putative interferon-alpha/beta receptor antagonist oxyphenylbutazone. In view of
      these observations, our current hypothesis is that the mitochondrial damage
      caused by exposure to interferon-alpha/beta may impair the ability of astrocytes
      to induce nitric oxide synthase activity on subsequent interferon-gamma exposure.
      These results may have implications for our understanding of the mechanisms
      responsible for the therapeutic effects of interferon-alpha/beta preparations in
      multiple sclerosis.

PMID- 9166752
TI  - Dinucleotide receptor modulation by protein kinases (protein kinases A and C) and
      protein phosphatases in rat brain synaptic terminals.
AB  - The diadenosine polyphosphates, diadenosine tetraphosphate and diadenosine
      pentaphosphate (Ap5A), can activate an ionotropic dinucleotide receptor that
      induces Ca2+ transients into synaptosomes prepared from rat brain. This receptor,
      also termed the P4 purinoceptor, is sensitive only to adenine dinucleotides and
      is insensitive to ATP. Studies on the modulatory role of protein kinase A (PKA),
      protein kinase C (PKC), and protein phosphatases on the response of diadenosine
      polyphosphate receptors were performed by measuring the changes in the
      intracellular Ca2+ levels with fura-2. Activation and inhibition of PKA were
      carried out by means of forskolin and the PKA inhibitory peptide (PKA-IP),
      respectively. The Ap5A response was inhibited by forksolin to 35% of control
      values, but PKA-IP induced an increase of 37%. The effect of PKC activation was
      similar to that observed for PKA. PKC stimulation with phorbol 12,13-dibutyrate
      produced an inhibition of 67%, whereas the PKC inhibitors staurosporine and PKC
      inhibitory peptide enhanced the responses elicited by Ap5A to 40% in both cases.
      Protein phosphatase inhibitors diminished the responses elicited by Ap5A to 17%
      in the case of okadaic acid, to 50% for microcystin, and to 45% in the case of
      cyclosporin A. Thus, the activity of dinucleotide receptors in rat brain
      synaptosomes appears to be modulated by phosphorylation/dephosphorylation. These
      processes could be of physiological significance in the control of transmitter
      release from neurons that are postsynaptic to nerves that release diadenosine
      polyphosphates.

PMID- 9166753
TI  - Increased solubility of high-molecular-mass neurofilament subunit by suppression
      of dephosphorylation: its relation to axonal transport.
AB  - To investigate the role of phosphorylation in the turnover and transport of
      neurofilament (NF) proteins in vivo, we studied their solubility properties and
      axonal transport in the rat sciatic nerve using phosphatase inhibitors to
      minimize dephosphorylation during preparation. About 20% of the 200-kDa subunit
      (NF-H) in the axon was soluble in the 1% Triton-containing buffer under the
      present conditions, whereas this amount was less and more variable in the absence
      of phosphatase inhibitors. The 68-kDa subunit (NF-L) was exclusively insoluble
      and not affected by the inhibitors. Such selective solubilization of NF-H by
      phosphorylation differed significantly from the in vitro phosphorylation with
      cyclic AMP-dependent protein kinase, which resulted in NF disassembly. The
      carboxy-terminal phosphorylation state of NF-H probed with the phosphorylation
      sensitive antibodies was also not directly related to solubility. The solubility
      of NF-H did not differ along the nerve. In contrast, the solubility of L
      [35S]methionine-labeled, transported NF-H was lowest at the peak of
      radioactivity. Higher solubility at the leading edge, regardless of its location
      along the nerve, indicates that NF-H solubility is positively correlated with the
      rate of NF transport.

PMID- 9166754
TI  - alpha2,6-Sialyltransferase gene transfection into a human glioma cell line (U373
      MG) results in decreased invasivity.
AB  - Glycosyltransferase gene transfection into cell lines has been an approach used
      successfully to elucidate the functional role of cell surface glycoconjugates. We
      have transfected the rat CMP-NeuAc:Galbeta1,4GlcNAc alpha2,6-sialyltransferase
      (EC 2.4.99.1) gene into a human, tumorigenic, glioma cell line, U373 MG. This
      transfection led to a marked inhibition of invasivity, alterations in adhesivity
      to fibronectin and collagen matrices, and inappropriately sialylated alpha3beta1
      integrin. Adhesion-mediated protein tyrosine phosphorylation was reduced in the
      transfectants despite increased expression of focal adhesion kinase, p125fak.
      Furthermore, the transfectants showed a distinct cell morphology, an increased
      number of focal adhesion sites, and different sensitivity to cytochalasin D
      treatment than control U373 MG cells. These results suggest that inappropriate
      sialylation of cell surface glycoconjugates, such as integrins, can change focal
      adhesion as well as adhesion-mediated signal transduction and block glioma cell
      invasivity in vitro.

PMID- 9166755
TI  - Effects of depolarization and NMDA antagonists on the role survival of cerebellar
      granule cells: a pivotal role for protein kinase C isoforms.
AB  - Primary cultures of cerebellar granule cells (CGCs) grown in high-K+ (25 mM; K25)
      medium progressively differentiate in vitro. Differentiation is noticeable after
      3-4 days in vitro (DIV) and reach a mature stage after 8 DIV. Longer cultivation
      of CGCs (>13 DIV) triggers the processes of spontaneous cell death. However, if
      cultured in normal physiological K concentration (5 mM; K5), a significant
      proportion of the cells dies by the end of the first week in culture. To address
      the role of protein kinase C (PKC) in the development of CGCs, we measured the
      kinase activity as well as the protein level of the kinase isoforms. As the K25
      CGC culture proceeded, the PKC activity time-dependently increased by 3.2-fold,
      reaching a steady state at 8 DIV. Western blot analysis using PKC isoform
      specific antibodies revealed an increase in levels of PKC alpha, gamma, mu,
      lambda, and iota from 2 to 8 DIV. A slight increase or decrease at 4 DIV was
      observed for PKC epsilon and betaII, respectively, whereas no significant change
      was observed for betaI. The isoforms of delta, theta, eta, and zeta were not
      detected. Comparing the 14 DIV cultures with the 10 DIV cultures, the
      immunoreactivities of PKC iota and epsilon were decreased, those of PKC alpha,
      betaI, betaII, gamma, and lambda were unchanged, whereas that of PKC mu was still
      increased. In K5 cultures, the immunoreactivity of each PKC isoform at 2-4 DIV
      was similar to that observed in K25 cells, although no remarkable differentiation
      features were observed. Coordinated with the appearance of cell death at 8 DIV in
      low-K+ cultures, levels of PKC alpha, mu, lambda, and iota, but not the others,
      were markedly decreased. The NMDA receptor antagonists MK-801 and 2-amino-5
      phosphopentanoic acid markedly prevented the age-induced apoptosis of CGCs, and
      the cells survived >18 DIV under these conditions. The cytoprotective effect of
      MK-801 was concomitant with the increases in levels of PKC gamma, lambda, iota,
      and mu at 10 and 14 DIV. In addition, the PKC epsilon level was increased at 14
      DIV but decreased at early stages, whereas PKC alpha, betaI, and betaII levels
      were unchanged, as compared with K25 culture alone. Taken together, induction and
      up-regulation of PKC isoforms may play an important role in the maintenance of
      CGC survival by depolarization and MK-801.

PMID- 9166756
TI  - Site-directed deletion of a 10-nucleotide domain of the 3'-untranslated region of
      the GLUT1 glucose transporter mRNA eliminates cytosolic protein binding in human
      brain tumors and induction of reporter gene expression.
AB  - The posttranscriptional regulation of GLUT1 glucose transporter gene expression
      may be mediated by specific interactions between cytosolic trans-acting factors
      and regulatory cis-elements within the 3'-untranslated regions (UTRs) of the
      GLUT1 mRNA. Recent studies demonstrate that experimental and human brain tumors
      express an 80-kDa protein that reacts with a specific sequence around nucleotide
      2,200 within the GLUT1 mRNA 3'-UTR. The 80-kDa protein is selectively expressed
      in hemangioblastoma, a tumor characterized by overexpression of GLUT1. The
      enhancer role of this GLUT1 3'-UTR cis-element was confirmed in the present
      studies using the luciferase expression vector pGL2 and site-directed deletion.
      Transfection of C6 glioma cells with pGL2 (containing nucleotides 2,100-2,300 of
      the bovine GLUT1 3'-UTR inserted at the Pfl MI site within the luciferase 3'-UTR)
      results in a fivefold increase in luciferase gene expression. Deletion of
      nucleotides 2,181-2,190 of the bovine GLUT1 3'-UTR, i.e., the putative binding
      site of the 80-kDa protein, completely eliminated the enhancement of luciferase
      activity in the transfected cells. Luciferase mRNA containing the putative cis
      element inserted in the 3'-UTR was transcribed, and after UV crosslinking, this
      mRNA complexed with the 80-kDa protein in cytosol of either C6 cells or
      hemangioblastoma. In contrast, this complex was undetected with either luciferase
      control mRNA or 10 nucleotide-deleted RNA. The present study provides evidence
      that nucleotides 2,181-2,190 of the bovine GLUT1 mRNA 3'-UTR forms a complex with
      brain tumor cytosolic proteins that serves to increase GLUT1 gene expression at
      the posttranscriptional level.

PMID- 9166757
TI  - Preferential potentiation of the effects of serotonin uptake inhibitors by 5-HT1A
      receptor antagonists in the dorsal raphe pathway: role of somatodendritic
      autoreceptors.
AB  - 5-HT1A autoreceptor antagonists enhance the effects of antidepressants by
      preventing a negative feedback of serotonin (5-HT) at somatodendritic level. The
      maximal elevations of extracellular concentration of 5-HT (5-HT(ext)) induced by
      the 5-HT uptake inhibitor paroxetine in forebrain were potentiated by the 5-HT1A
      antagonist WAY-100635 (1 mg/kg s.c.) in a regionally dependent manner (striatum >
      frontal cortex > dorsal hippocampus). Paroxetine (3 mg/kg s.c.) decreased
      forebrain 5-HT(ext) during local blockade of uptake. This reduction was greater
      in striatum and frontal cortex than in dorsal hippocampus and was counteracted by
      the local and systemic administration of WAY-100635. The perfusion of 50
      micromol/L citalopram in the dorsal or median raphe nucleus reduced 5-HT(ext) in
      frontal cortex or dorsal hippocampus to 40 and 65% of baseline, respectively. The
      reduction of cortical 5-HT(ext) induced by perfusion of citalopram in midbrain
      raphe was fully reversed by WAY-100635 (1 mg/kg s.c.). Together, these data
      suggest that dorsal raphe neurons projecting to striatum and frontal cortex are
      more sensitive to self-inhibition mediated by 5-HT1A autoreceptors than median
      raphe neurons projecting to the hippocampus. Therefore, potentiation by 5-HT1A
      antagonists occurs preferentially in forebrain areas innervated by serotonergic
      neurons of the dorsal raphe nucleus.

PMID- 9166758
TI  - Down-regulation of 5-hydroxytryptamine7 receptors by dexamethasone in rat
      frontocortical astrocytes.
AB  - Astrocytes derived from rat frontal cortex contain 5-hydroxytryptamine7 (5-HT)7
      receptors positively coupled to adenylyl cyclase. In the present study, we
      investigated the effects of glucocorticoids on adenylyl cyclase activity and 5
      HT7 receptor gene expression in astrocytes. Addition of dexamethasone (0.01-100
      nM, 12-72 h) to the culture medium decreased cyclic AMP formation induced by 5-HT
      in a time- and concentration-dependent manner. Dexamethasone treatment (10 nM, 48
      h) reduced maximum responses of cyclic AMP formation induced by 5-HT and 5
      carboxamidotryptamine without alterations in the EC50 value. In contrast,
      treatment with the mineralocorticoid aldosterone (48 h) had no significant
      effects on 5-HT-induced cyclic AMP formation with concentrations up to 10 nM. It
      was observed that dexamethasone treatment (1-100 nM, 3-72 h) also decreased the
      expression of 5-HT7 receptor mRNA, using reverse transcription and polymerase
      chain reaction analysis. A significant reduction in expression of 5-HT7 mRNA
      appeared at 3 h of dexamethasone treatment and reached a maximum at 6 h of
      treatment. On the other hand, dexamethasone treatment (10 nM, 48 h) did not
      affect basal levels of cyclic AMP and cyclic AMP synthesis stimulated by
      isoproterenol, N-ethylcarboxamidoadenosine, cholera toxin, and forskolin. These
      results suggest that dexamethasone decreases the expression of the 5-HT7 receptor
      gene and, consequently, 5-HT7 receptor-mediated signal transduction in
      frontocortical astrocytes.

PMID- 9166759
TI  - Heterogeneity of beta-adrenoceptors in guinea-pig brain: radioligand binding and
      cyclic nucleotide generation.
AB  - In this report, we have examined the radioligand binding and second messenger
      signalling characteristics of beta-adrenoceptors in the guinea-pig brain. [125I]
      Iodocyanopindolol ([125I]ICYP)-labelled sites in the cerebellum and cerebral
      cortex were of similar densities (Bmax 34 and 24 fmol x mg(-1)) and affinities
      (K(D) 20 and 55 pM), respectively. Analysis of competition for [125I]ICYP binding
      in the cerebellum was compatible with the presence of a beta2-adrenoceptor. In
      this tissue, isoprenaline evoked a cyclic AMP stimulation, and also potentiated
      cyclic GMP accumulations evoked in the presence of a nitric oxide donor,
      consistent with mediation via a beta2-adrenoceptor. The [125I]ICYP binding
      profile in the cerebral cortex did not comply with those previously described for
      beta-adrenoceptor subtypes, and isoprenaline failed to alter significantly cyclic
      AMP accumulation in the cerebral cortex, hippocampus, or neostriatum, even in the
      presence of forskolin or a phosphodiesterase inhibitor. Isoprenaline was also
      without effect on cyclic GMP accumulation or phosphoinositide turnover in the
      cerebral cortex. These results suggest that the guinea-pig cerebellum expresses a
      functional beta2-adrenoceptor coupled to cyclic AMP generation, and potentiation
      of cyclic GMP accumulation. However, the guinea-pig cerebral cortex displays
      binding sites that exhibit beta-adrenoceptor-like pharmacology but fail to show
      functional coupling to cyclic AMP, cyclic GMP, or phosphoinositide signalling
      systems.

PMID- 9166760
TI  - Modulation of serotonin transporter activity by a protein kinase C activator and
      an inhibitor of type 1 and 2A serine/threonine phosphatases.
AB  - We studied the effects of 12-O-tetradecanoylphorbol 13-acetate (TPA), a protein
      kinase C (PKC) activator, and calyculin A (CLA), an inhibitor of type 1 and 2A
      serine/threonine phosphatases, on serotonin uptake by a human placenta
      choriocarcinoma cell line (BeWo) and COS-7 cells expressing recombinant serotonin
      transporter (SET). In BeWo cells, treatment with TPA decreased imipramine
      sensitive serotonin uptake with a reduction in Vmax without affecting Km. CLA
      also decreased imipramine-sensitive serotonin uptake in a manner similar to that
      of TPA. TPA and CLA also decreased the uptake activity of recombinant SET
      expressed in COS-7 cells as seen in BeWo cells. These effects of TPA and CLA were
      reversed by staurosporine, a protein kinase inhibitor. To elucidate whether the
      inhibitory effects of TPA and CLA were due to direct phosphorylation of SET by
      PKC, site-directed mutagenesis of five putative PKC phosphorylation sites in SET
      was performed. Serotonin uptake was also down-regulated by TPA and CLA in all
      nine mutants, suggesting that these inhibitory modulation of SET activity did not
      act via direct phosphorylation of SET by PKC.

PMID- 9166761
TI  - The activating dual phosphorylation of MAPK by MEK is nonprocessive.
AB  - Activation of mitogen-activated protein kinases (MAPKs), also known as
      extracellular-signal-regulated kinases (ERKs), by MAPK/extracellular protein
      kinase kinases (MEKs) requires phosphorylation at two sites. The first step in
      MAPK activation by MEK must be the formation of a MEK x MAPK enzyme-substrate
      complex, followed by phosphorylation producing monophosphorylated MAPK (pMAPK).
      Subsequently, one of two events may occur. (1) MEK catalyzes the second and fully
      activating phosphorylation of MAPK, producing ppMAPK (a processive mechanism).
      (2) The complex of MEK x pMAPK dissociates before the second phosphorylation
      occurs, full activation requiring a reassociation of pMAPK with MEK (a
      nonprocessive or distributive mechanism). Simulations indicate that these two
      mechanisms predict different kinetics of MAPK activation. Specifically, the
      nonprocessive mechanism predicts that there will be a paradoxical decrease in the
      rate of MAPK activation as the MAPK concentration is increased. The present study
      uses p42 MAPK, also known as ERK2, and MEK1 as representatives of their
      respective classes of enzymes. We find that increasing the ERK2 concentration
      decreases the rate of activation by a mechanism which does not involve inhibition
      of MEK1 function. The accumulation of the active, doubly phosphorylated ERK2
      (ppERK2) was directly assessed using a phosphorylation-state-specific antibody.
      The rate of accumulation of ppERK2 is decreased by increasing the ERK2
      concentration. Therefore, the mechanism of ERK2 activation by MEK1 in vitro is
      nonprocessive.

PMID- 9166762
TI  - Spontaneous DNA lesions poison human topoisomerase IIalpha and stimulate cleavage
      proximal to leukemic 11q23 chromosomal breakpoints.
AB  - Topoisomerase II-targeted drugs, such as etoposide, "poison" this enzyme and kill
      cells by increasing levels of covalent topoisomerase II-cleaved DNA complexes. In
      spite of the success of this drug in the treatment of human cancers, a
      significant proportion of patients treated with etoposide eventually develop
      secondary leukemias that are characterized by translocations at chromosome band
      11q23. Since similar translocations are associated with primary leukemias in
      previously untreated infants, we questioned whether they could also be triggered
      by the actions of "endogenous topoisomerase II poisons". Recent studies, which
      demonstrated that several forms of spontaneous DNA damage stimulate cleavage
      mediated by Drosophila topoisomerase II, suggest that DNA lesions may act as
      these endogenous poisons. Therefore, to determine whether the ability to
      recognize spontaneous DNA damage has been conserved from this lower eukaryote to
      mammalian species, the effects of apurinic sites, apyrimidinic sites, and
      deaminated cytosine residues on human topoisomerase IIalpha were assessed. All
      three lesions were potent poisons of the human enzyme and stimulated cleavage
      when located within the four-base overhang generated by enzyme-mediated DNA
      scission. Furthermore, these lesions increased levels of cleavage at five sites
      proximal to 11q23 translocation breakpoints and did so with an efficacy that was
      comparable to or greater than that of therapeutic concentrations of etoposide.
      Although the physiological relevance of these findings has yet to be established,
      they suggest a potential role for endogenous topoisomerase II poisons in the
      initiation of leukemic chromosomal breakpoints.

PMID- 9166763
TI  - Structure of a DNA-bisdaunomycin complex.
AB  - The application of detailed structural data bases has now culminated in the
      successful design of a new generation of bisanthracyclines that form ultratight
      DNA complexes [Chaires, J. B., Leng, F., Przewloka, T., Fokt, I., Ling, Y. H.,
      Perez-Soler, R., & Priebe, W. (1997) J. Med. Chem. 40, 261-266]. Daunomycin
      dimers were designed to bind to DNA in complexes resembling those of monomers
      intercalated at adjacent sites. The goal of the work described here was to
      determine, with X-ray crystallography, if a potent member of this newly designed
      and synthesized class of bisanthracyclines (WP631) binds as intended. WP631 is
      composed of two daunomycin molecules, linked N3' to N3' by a xylyl group. We have
      solved the 2.2 A X-ray crystal structure of a complex of WP631 bound to
      [d(CGATCG)]2. We demonstrate, on a detailed molecular level, that the WP631
      design strategy is a success. The structures of WP631 and two daunomycin
      molecules bound to [d(CGATCG)]2 provide the unprecedented opportunity for
      detailed comparison of mono- and bis-intercalated complexes of the same
      chromophore, allowing us to distinguish effects of mono-intercalation from those
      of bis-intercalation. Differences are focused primarily in the centers of the
      complexes. DNA unwinding and other helical distortions propagate more efficiently
      to the center of the WP631 complex than to the center of the daunomycin complex.

PMID- 9166764
TI  - Purification and characterization of the DNA polymerase alpha associated
      exonuclease: the RTH1 gene product.
AB  - We report here the purification and mechanistic characterization of a 5'-3'
      exonuclease associated with DNA polymerase alpha from the yeast Saccharomyces
      cerevisiae. Earlier, we identified a 5' --> 3' exonuclease activity that
      copurified with yeast DNA polymerase alpha-primase in a multiprotein complex
      [Biswas, E. E., et al. (1993) Biochemistry, 32, 3020-3027]. Peptide sequence
      analysis of the purified 47 kDa exonuclease was carried out, and the peptide
      sequence was found to be identical to the S. cerevisiae gene YKL510 encoded
      polypeptide, which is also known as yeast RAD2 homolog 1 or RTH1 nuclease. The
      native exonuclease also had strong flap endonuclease activity similar to that
      observed with RTH1 nuclease and homologous yeast (RAD2) and mammalian enzymes.
      During our studies, we have discovered certain unique features of the mechanism
      of action of the native RTH1 nuclease. Studies presented here indicated that the
      exonuclease had specific pause sites during its 5'-3' exonuclease nucleotide
      excision. These pause sites were easily detected with long (approximately 50 bp)
      oligonucleotide substrates during exonucleolytic excision by the formation of a
      discontinuous ladder of excision product. We have further analyzed the mechanism
      of generation of the pause sites, as they could occur through a number of
      different pathways. Alignment of the pause sites with the nucleotide sequence of
      the oligonucleotide substrate indicated that the pause sites were dependent on
      the nucleotide sequence. Our analysis revealed that RTH1 nuclease pauses
      predominantly at G:C rich sequences. With poly(dA):oligo(dT)50 as substrate, the
      exonucleolytic products formed a continuous ladder with no evidence of pausing.
      The G:C rich DNA sequences are thermodynamically more stable than the A:T rich
      sequences, which may be in part responsible for pausing of the RTH1 5' --> 3'
      exonuclease at these sites.

PMID- 9166765
TI  - Stimulation of RTH1 nuclease of the yeast Saccharomyces cerevisiae by replication
      protein A.
AB  - The RTH1 nuclease is involved in the replication of chromosomal DNA as well as in
      the repair of DNA damage. Replication protein A (RPA) is also an integral part of
      the DNA replication and repair processes. We have investigated the roles(s) of
      RPA in the function of RTH1 nuclease, including its structure specific
      endonuclease activity. Initial in vitro studies, which employed a "flap" or a
      "pseudo Y" substrate containing a short 14 bp duplex region, showed the effect of
      RPA to be minimal or inhibitory. As RPA inhibition is unwarranted for a protein
      participating in the DNA replication process, we have further investigated the
      mechanism of such inhibition. Alternate flap and pseudo Y substrates with a long
      duplex region (50 bp) were prepared using M13mp19 ssDNA and synthetic
      oligonucleotides. Yeast RPA stimulated the endonuclease activity of RTH1
      endonuclease with these substrates in a dose-dependent manner. Kinetic analysis
      suggested that yRPA exerted a bipartite effect on the nuclease reaction: (i) the
      "load time" of RTH1 nuclease onto the DNA substrate decreased from approximately
      5 to 2 min in the presence of RPA, and (ii) following initiation of the nuclease
      reaction, the initial rate of the reaction increased 10-fold in the presence of
      yRPA. Further analysis of the interaction of RPA with various endonuclease
      substrates indicated that RPA has a weak helix destabilizing effect and could
      melt small, 14 bp, regions of duplex DNA. RTH1 endonuclease cleaves the DNA
      strand at the junction of single- and double-stranded DNA; consequently, the
      observed inhibition with small duplex substrates was likely due to duplex
      melting. Our studies also demonstrated that RPA stimulated the RNase H activity
      of RTH1 nuclease significantly. In both instances (RTH1 endonuclease and RNase
      H), the stimulation may involve a specific interaction of RPA with the RTH1
      nuclease rather than a structural positioning of the DNA substrate by RPA.

PMID- 9166766
TI  - Use of the transglutaminase reaction to study the dissociation of histone N
      terminal tails from DNA in nucleosome core particles.
AB  - We have recently shown that core histones are glutaminyl substrates for
      transglutaminase (TGase) and that when native nucleosome cores are incubated with
      monodansylcadaverine (DNC) as donor amine, this fluorescent probe is incorporated
      into Gln5 and Gln19 of H3 and in Gln22 of H2B [Ballestar et al. (1996) J. Biol.
      Chem. 271, 18817-18825]. In the present paper, we report that the cause by which
      Gln22 of H2B is modified in nucleosomes but not in the free histone is the
      interaction of the region containing that glutamine with DNA. We have used the
      specificity of the TGase reaction to study the changes induced by increasing
      ionic strength in the interaction between the histone N-terminal tails and
      nucleosome DNA by two different approaches. First, the reactivity of the histone
      tail glutamines was employed to monitor changes in the interactions between the
      regions containing these residues and DNA. Second, by using reconstituted
      nucleosome core particles containing either H2B modified with DNC by the TGase
      reaction at Gln22 or H3 modified with the same procedure at Gln5 and Gln19, the
      dissociation of the histone tails was followed by the decrease of the
      fluorescence anisotropy of the probe. These methods allowed us to describe two
      ionic strength dependent structural transitions of the histone tails not reported
      to date. In the case of H2B, the first one occurs at very low ionic strength, and
      it can be assigned to an increase in the mobility of Gln22. The second one
      results in the cooperative release of a region of the tail that includes lysine
      residues next to Gln22, and it is followed by the overall release of the entire
      tail, described by other workers.

PMID- 9166767
TI  - Solution structure of a polypeptide from the N terminus of the HIV protein Nef.
AB  - Nef is a 27 kDa myristylated phosphoprotein expressed early in infection by HIV.
      The N terminus of Nef is thought to play a vital role in the functions of this
      protein through its interactions with membrane structures. The solution structure
      of a 25-residue polypeptide corresponding to the N terminus of Nef (Nef1-25) has
      been investigated by 1H NMR spectroscopy. In aqueous solution at pH 4.8 and 281
      K, this peptide underwent conformational averaging, with Pro13 existing in cis
      and trans conformations in nearly equal proportions. In methanol solution,
      however, the peptide adopted a well-defined alpha-helical structure from residues
      6 to 22, with the N- and C-terminal regions having a less ordered structure. On
      the basis of a comparison of chemical shifts and NOEs, it appeared that this
      helical structure was maintained in aqueous trifluoroethanol (50% v/v) and to a
      lesser extent in a solution of SDS micelles. When the N-acetyl group was replaced
      by either an N-myristyl or a free ammonium group, there was little effect on the
      three-dimensional structure of the peptide in methanol; deamidation of the C
      terminus also had no effect on the structure in methanol. In water, the
      myristylated peptide aggregated. The similarity between the sequences of Nef1-25
      and melittin is reflected in the similar structures of the two molecules,
      although the N-terminal helix of melittin is more defined. This similarity in
      structure raises the possibility that Nef1-25 not only interacts with membranes
      but also may be capable of disrupting them and causing cell lysis. This type of
      interaction could contribute at least in part to the killing of bystander cells
      in lymphoid tissues during HIV infection.

PMID- 9166768
TI  - Solution structures of 5-fluorouracil-substituted RNA duplexes containing G-U
      wobble base pairs.
AB  - The structures and stabilities of three RNA duplexes that differed only in the
      position of 5-fluorouridine (FUrd) substitution were elucidated using NMR
      spectroscopy and UV hyperchromicity studies to determine if FUrd substitution
      altered the structure or stability of RNA duplexes that contained G-U base pairs.
      The duplexes investigated corresponded to the region of the U4-U6 snRNA complex
      that contained the 5' terminus of U4 snRNA. The control duplex contained a G-U
      wobble base pair and also a G-A mismatched base pair. FUrd was substituted in one
      duplex at the G-U wobble base pair and in the second duplex at an A-U base pair
      adjacent to the wobble base pair. FUrd substitution slightly destabilized the
      duplex that contained a G-FU base pair but stabilized the duplex that contained
      an A-FU base pair. NOESY spectra were used to determine interproton distances,
      and these distance constraints were used in a restrained molecular dynamics
      protocol to determine the three-dimensional structures of these RNA duplexes.
      Analyses of helical parameters, backbone torsion angles, and rms deviations
      between the final structures revealed no systematic differences due to FUrd
      substitution in RNA duplexes that contained G-U base pairs. The G-FU base pair
      adopted wobble geometry, while the G-A mismatch formed a sheared base pair. NOESY
      spectra in H2O solution revealed the imino 1H from FUrd exchanged more rapidly
      with solvent than did the Urd imino 1H but did not show the G-FU base pair
      adopted an ionized structure. Reduced stacking occurred for the G-FU base pair
      relative to the G-U base pair in the time-averaged structure, and this, rather
      than ionization of the base pair, was responsible for the slight destabilization
      of the duplex that contained the G-FU base pair.

PMID- 9166769
TI  - Nuclear accumulation of HMG2 protein is mediated by basic regions interspaced
      with a long DNA-binding sequence, and retention within the nucleus requires the
      acidic carboxyl terminus.
AB  - High mobility group 2 (HMG2) protein is ubiquitously distributed in the nucleus
      of higher eukaryotic cells. Accumulation of an HMG2-beta-galactosidase fusion
      protein expressed in COS-7 cells suggested active transport of HMG2 protein into
      the nucleus after translation in the cytoplasm. Deletion analysis of the HMG2
      sequence in the HMG2-beta-galactosidase fusion protein indicated that basic
      regions interspaced with the long DNA-binding sequence in HMG2, called the HMG1/2
      box, are necessary for the nuclear accumulation of HMG2. The close configuration
      of basic regions at both ends of the DNA-binding sequence in the tertiary
      structure may function as the nuclear localization signal. This novel nuclear
      localization signal structure is different from typical ones such as the single
      or bipartite basic cluster in many nuclear proteins. A portion of the HMG2
      molecule remained in the cytoplasm after translation. Interspecies heterokaryon
      assay demonstrated that the acidic carboxyl terminus of HMG2 was necessary for
      retention of the protein in the nucleus.

PMID- 9166771
TI  - Crystal structure at 2.0 A resolution of phosphoribosyl anthranilate isomerase
      from the hyperthermophile Thermotoga maritima: possible determinants of protein
      stability.
AB  - The structural basis of thermostability of proteins is of great scientific and
      biotechnological interest. Differences in the X-ray structues of orthologous
      proteins from hyperthermophilic and mesophilic organisms can indicate crucial
      stabilizing interactions. To this end the crystal structure of dimeric
      phosphoribosyl anthranilate isomerase from the hyperthermophile Thermotoga
      maritima (tPRAI) was determined using phases derived from the isomorphous
      replacement method and was refined at 2.0 A resolution. The comparison to the
      known 2.0 A structure of PRAI from Escherichia coli (ePRAI) shows that tPRAI has
      the complete TIM- or (beta alpha)8-barrel fold, whereas helix alpha5 in ePRAI is
      replaced by a loop. The subunits of tPRAI associate via the N-terminal faces of
      their central beta-barrels. Two long, symmetry-related loops that protrude
      reciprocally into cavities of the other subunit provide for multiple hydrophobic
      interactions. Moreover, the side chains of the N-terminal methionines and the C
      terminal leucines of both subunits are immobilized in a hydrophobic cluster, and
      the number of salt bridges is increased in tPRAI. These features appear to be
      mainly responsible for the high thermostability of tPRAI. In contrast to other
      hyperthermostable enzymes, tPRAI at 25 degrees C is catalytically more efficient
      than ePRAI, mainly due to its small K(M) value for the substrate [Sterner, R.,
      Kleemann, G. R., Szadkowski, H., Lustig, A., Hennig, M., & Kirschner, K. (1996)
      Protein Sci. 5, 2000-2008]. The increased number of hydrogen bonds between the
      phosphate ion and tPRAI compared to ePRAI could be responsible for this effect.

PMID- 9166770
TI  - Solution structure of the actinorhodin polyketide synthase acyl carrier protein
      from Streptomyces coelicolor A3(2).
AB  - The solution structure of the actinorhodin acyl carrier protein (act apo-ACP)
      from the polyketide synthase (PKS) of Streptomyces coelicolor A3(2) has been
      determined using 1H NMR spectroscopy, representing the first polyketide synthase
      component for which detailed structural information has been obtained. Twenty
      four structures were generated by simulated annealing, employing 699 distance
      restraints and 94 dihedral angle restraints. The structure is composed,
      principally, of three major helices (1, 2, and 4), a shorter helix (3) and a
      large loop region separating helices 1 and 2. The structure is well-defined,
      except for a portion of the loop region (residues 18-29), the N-terminus (1-4),
      and a short stretch (57-61) in the loop connecting helices 2 and 3. The RMS
      distribution of the 24 structures about the average structure is 1.47 A for
      backbone atoms, 1.84 A for all heavy atoms (residues 5-86), and 1.01 A for
      backbone atoms over the helical regions (5-18, 41-86). The tertiary fold of act
      apo-ACP shows a strong structural homology with Escherichia coli fatty acid
      synthase (FAS) ACP, though some structural differences exist. First, there is no
      evidence that act apo-ACP is conformationally averaged between two or more states
      as observed in E. coli FAS ACP. Second, act apo-ACP shows a disordered N-terminus
      (residues 1-4) and a longer flexible loop (19-41 with 19-29 disordered) as
      opposed to E. coli FAS ACP where the N-terminal helix starts at residue 3 and the
      loop region is three amino acids shorter (16-35). Most importantly, however,
      although the act apo-ACP structure contains a hydrophobic core, there are in
      addition a number of buried hydrophilic groups, principally Arg72 and Asn79, both
      of which are 100% conserved in the PKS ACPs and not the FAS ACPs and may
      therefore play a role in stabilizing the growing polyketide chain. The structure
      function relationship of act ACP is discussed in the light of these structural
      data and recent genetic advances in the field.

PMID- 9166772
TI  - Structures of calmodulin and a functional myosin light chain kinase in the
      activated complex: a neutron scattering study.
AB  - Calmodulin (CaM) is the major intracellular receptor for Ca2+ and is responsible
      for the Ca2+-dependent regulation of a wide variety of cellular processes via
      interactions with a diverse array of target enzymes. Our current view of the
      structural basis for CaM enzyme activation is based on biophysical studies of CaM
      complexed with small peptides that model CaM-binding domains. A major concern
      with interpreting data from these structures in terms of target enzyme activation
      mechanisms is that the larger enzyme structure might be expected to impose
      constraints on CaM binding. Full understanding of the molecular mechanism for CaM
      dependent enzyme activation requires additional structural information on the
      interaction of CaM with functional enzymes. We have utilized small-angle X-ray
      scattering and neutron scattering with contrast variation to obtain the first
      structural view of CaM complexed with a functional enzyme, an enzymatically
      active truncation mutant of skeletal muscle myosin light chain kinase (MLCK). Our
      data show that CaM undergoes an unhindered conformational collapse upon binding
      MLCK and activates the enzyme by inducing a significant movement of the kinase's
      CaM binding and autoinhibitory sequences away from the surface of the catalytic
      core.

PMID- 9166773
TI  - Regioselective effect of zwitterionic DNA substitutions on DNA alkylation:
      evidence for a strong side chain orientational preference.
AB  - The incorporation of zwitterionic residues (5-substituted omega-aminoalkyl-2'
      deoxypyrimidines) into DNA has been reported to bend DNA as measured by aberrant
      gel mobility [Strauss et al. (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 9515-9520].
      Herein we report that DNA methylation by N-methyl-N-nitrosourea at N7-guanine is
      regioselectively inhibited by point substitutions of the zwitterionic residues 5
      (6-aminohexyl)-2'-deoxycytidine, 5-(6-aminohexyl)-2'-deoxyuridine, or 5-(3
      aminopropyl)-2'-deoxyuridine. No inhibition is observed for DNA methylation by
      dimethyl sulfate. On the basis of inhibition patterns for methylation with the
      different zwitterionic substitutions and the different length tethers, the omega
      aminoalkyl side chains prefer to adopt a conformation that points them toward the
      3'-base. Molecular modeling grid searches, coupled with energy minimizations, and
      simulated annealing molecular dynamics studies indicate that unfavorable steric
      interactions with the 5'-base and backbone, as well as stabilizing electrostatic
      interactions with electronegative atoms on the 3'-side, are responsible for the
      observed conformational preference. No evidence for association of the cationic
      side chain with the phosphate backbone is observed. The observed bending of DNA
      induced by the tethered ammonium ions may simply arise from their localization in
      the major groove.

PMID- 9166774
TI  - Modified antisense oligonucleotides directed against tumor necrosis factor
      receptor type I inhibit tumor necrosis factor alpha-mediated functions.
AB  - Tumor necrosis factor alpha (TNF alpha), a polypeptide produced by activated
      macrophages, is a highly pleiotropic cytokine which elicits inflammatory and
      immunological reactions. The binding of TNF alpha to tumor necrosis factor
      receptor type I (TNFRI) is considered the initial step responsible for some of
      the multiple biological functions mediated by TNF alpha. The role of TNF alpha as
      an inflammatory mediator through human TNFRI makes TNFRI an attractive target for
      intervention in both acute and chronic inflammatory diseases. In this study, we
      have identified partial phosphorothioate oligodeoxyribonucleotides (ODNs)
      containing C-5 propynyl or hexynyl derivatives of 2'-deoxyuridine which
      specifically inhibited TNFRI and subsequently inhibited the functions of TNF
      alpha mediated through TNFRI. The most active ODNs were directed against the 3'
      poly adenylation signal site on the TNFRI mRNA, and in a cellular assay, gene
      specific antisense inhibition occurred in a dose-dependent fashion at
      submicromolar concentrations, in the presence of Cellfectin. The inhibition of
      gene expression correlated with the binding affinity of the ODN for the target
      mRNA. The ODNs lowered TNFRI protein levels and TNF alpha-mediated functions by
      specifically reducing levels of TNFRI mRNA. These anti-TNFRI ODNs offer a novel
      approach for controlling biological functions of TNF alpha and may be useful as
      human therapeutic agents for treating diseases in which TNF alpha has been
      implicated.

PMID- 9166775
TI  - Probing contacts to the DNA backbone in the trp repressor-operator sequence
      specific protein-nucleic acid complex using diastereomeric methylphosphonate
      analogues.
AB  - Fourteen analogue DNA sequences containing the trp operator sequence and a single
      diastereomeric methylphosphonate linkage are each prepared from the
      stereochemically pure nucleoside methylphosphonate dimer building block, prepared
      as a phosphoramidite. The analogue sequences are shown to be single diastereomers
      on the basis of HPLC analysis of the digestion mixture; in each case, only a
      single diastereomeric dimer is present. These analogue sequences can be used
      effectively to probe for interactions to either of the prochiral phosphate
      oxygens as illustrated by their use to identify critical interactions in the trp
      repressor-operator complex. In a number of cases, the pairs of diastereomeric
      analogue sequences exhibit variable binding affinities that can be used to
      identify one of the prochiral phosphate oxygens as a critical site for complex
      stabilizing interactions. Upon the basis of dissociation constants, apparent
      incremental binding energies are assigned to specific interactions. In all but
      one example, these identified sites for interactions to the phosphate backbone
      can be correlated with contacts implicated by the crystal structure analysis of
      the trp repressor-operator complex.

PMID- 9166776
TI  - Exploiting nucleotide thiophosphates to probe mechanistic aspects of Escherichia
      coli DNA gyrase.
AB  - The interaction of DNA gyrase with ATP has been probed using a range of
      thiophosphate ATP analogs. ATP gammaS is not detectably hydrolyzed by gyrase but
      can support limited, probably catalytic, DNA supercoiling. ATP gammaS is a good
      inhibitor of both ATP hydrolysis and ATP-supported supercoiling. In contrast,
      both ATP alphaS(Rp) and ATP betaS(Rp) have been shown to be good substrates for
      the ATPase reaction of gyrase and to support catalytic DNA supercoiling. The
      corresponding Sp diastereoisomers do not support significant levels of
      supercoiling and are not readily hydrolyzed, but are shown to be reasonable
      inhibitors of gyrase. For ATP alphaS(Rp), the supercoiling and ATPase activities
      appear to be tightly coupled with the thionucleotide being apparently a better
      substrate than ATP in terms of both DNA supercoiling and nucleotide hydrolysis.
      In the case of ATP betaS(Rp), DNA supercoiling and nucleotide hydrolysis appear
      to be uncoupled in that ATP betaS(Rp) is almost as good a substrate as ATP for
      the ATPase reaction of both intact gyrase and the 43 kDa GyrB fragment, whereas
      it only supports slow DNA supercoiling; the mechanistic consequences of these
      observations are discussed in terms of a new model for energy coupling in gyrase.
      DNA gyrase has been shown to be capable of catalyzing DNA supercoiling in the
      presence of Mg2+, Ca2+, and Mn2+ but not Zn2+, Co2+, Ni2+, or Cd2+. The
      pronounced diastereoselectivity seen in both the DNA supercoiling and ATPase
      activity with ATP alphaS and ATP betaS together with evidence from the X-ray
      structure of the 43 kDa GyrB-ADPNP-Mg complex is consistent with metal ion
      coordination at both of these sites, and probably to the gamma-phosphoryl center
      during turnover. Thus, the absolute configuration of the catalytically active
      Mg2+-ATP complex is likely to involve coordination to the pro-S oxygens at both P
      alpha and P beta, leading to the alpha,beta,gamma-tridentate Mg-ATP complex with
      the lambda-exo configuration.

PMID- 9166777
TI  - Misincorporation of dNTPs opposite 1,N2-ethenoguanine and 5,6,7,9-tetrahydro-7
      hydroxy-9-oxoimidazo[1,2-a]purine in oligonucleotides by Escherichia coli
      polymerases I exo- and II exo-, T7 polymerase exo-, human immunodeficiency virus
      1 reverse transcriptase, and rat polymerase beta.
AB  - 1,N2-Ethenoguanine (1,N2-epsilon-Gua) and 5,6,7,9-tetrahydro-7-hydroxy-9
      oxoimidazo[1,2-a]purine (HO-ethanoGua) are two modified bases formed in the
      reaction of DNA with 2-chlorooxirane, the epoxide derivative of vinyl chloride.
      The oligonucleotides (19-mers), 5'-CAGTGGGTG*TCCGAATTGA-3', were prepared, with
      each of these modified bases substituted for G at G*. HO-ethanodeoxyguanosine
      exists predominantly as a mixture of diastereomers of the closed cyclic
      hemiaminal form, 5,6,7,9-tetrahydro-7-hydroxy-9-oxoimidazo[1,2-a]purine, shown by
      H2(18)O experiments to be in equilibrium with the open form, N2-(2-oxoethyl)Gua.
      Both adducts retarded the 3'-extension of a complementary 10-mer primer by all of
      the polymerases examined, but in every case, some full-length product was
      obtained. Nucleotide sequence analysis indicated misincorporation of dGTP and
      dATP across from both 1,N2-epsilon-Gua and HO-ethanoGua, with the extent varying
      considerably among the polymerases. Similar results were obtained when the
      abilities of the polymerases to incorporate a single dNTP were evaluated. In
      addition, -1 and -2 base frame shifts were detected with both 1,N2-epsilon-Gua
      and HO-ethanoGua with some of the polymerases. Steady-state kinetic experiments
      with Escherichia coli polymerase I exo- and T7 polymerase exo-/thioredoxin showed
      large decreases in k(cat) for all dNTP incorporations compared to the normal G x
      dCTP pair and high misincorporation frequencies for dATP and dGTP with both
      adducts (compared to dCTP). Collectively, the results indicate that both of these
      adducts have considerable miscoding potential with some of these polymerases,
      that there are a number of differences between the 1,N2-epsilon-Gua and HO
      ethanoGua adducts (which formally differ only in the presence of the elements of
      water), and that misincorporation of dNTPs at a single modified base can vary
      considerably among different polymerases even in the absence of exonuclease
      activity.

PMID- 9166779
TI  - The angle between the anticodon and aminoacyl acceptor stems of yeast tRNA(Phe)
      is strongly modulated by magnesium ions.
AB  - Many tRNAs undergo tertiary folding transitions at temperatures well below the
      main thermally induced (hyperchromic) transition. Such transitions are
      essentially isochromic and isoenthalpic and display an absolute requirement for
      divalent cations; however, the nature of the structural transition is not known
      for any tRNA. Using a combination of transient electric birefringence (TEB) and
      gel electrophoretic measurements, we have characterized the influence of
      magnesium ions on the apparent angle between the anticodon and acceptor stems of
      a yeast tRNA(Phe) construct. TEB is a particularly sensitive method for
      quantifying the bends introduced in RNA by various nonhelix elements. In the
      current instance, the tRNA construct comprises an unmodified tRNA(Phe) molecule
      in which the anticodon and acceptor stems have been extended by approximately 70
      bp to more effectively "report" the interstem angles. Upon the addition of sub
      millimolar concentrations of magnesium ions, the tRNA core undergoes a
      substantial rearrangement in tertiary structure, passing from an open form with
      an apparent interstem angle of approximately 150 degrees to a conformation with
      an interstem angle of approximately 70 degrees (200 microM Mg2+). Further
      addition of magnesium ions results in a minor adjustment of the apparent
      interstem angle to approximately 80-90 degrees, in line with earlier results.
      Finally, the magnesium-induced structural transition is essentially isochromic,
      in agreement with previous observations with native tRNAs. The current results
      suggest that changes in local divalent ion concentration in the ribosome could
      profoundly affect the global conformations of tRNAs during the translation cycle.

PMID- 9166778
TI  - Identification of a motif within the 5' regulatory region of pS2 which is
      responsible for AP-1 binding and TCDD-mediated suppression.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related compounds modulate several
      endocrine systems by altering hormone synthesis, enhancing ligand metabolism, and
      down-regulating receptor levels/binding activity. Previous studies have
      demonstrated that TCDD inhibits the 17beta-estradiol (E2)-induction of pS2, a
      human breast cancer prognostic marker. This inhibition occurs at the gene
      expression level and is Ah receptor (AhR)-mediated. Analysis of the 5' regulatory
      region has identified three motifs which resemble dioxin response element (DRE)
      core sequences. pS2-regulated luciferase deletion constructs identified the DRE
      like motif located at -527 to -514 as being required for TCDD-mediated
      suppression. A point mutation within this core motif (T-518C) abolished the
      inhibition by TCDD while UV-induced protein-DNA cross-linking and competitive gel
      retardation assays demonstrated AhR complex binding to this motif. Further study
      of this region also revealed an adjacent putative AP-1 site, diverging by one
      base pair from the consensus sequence. Gel retardation assays using TPA-treated
      MCF-7 cell nuclear extracts showed an induced complex binding to the AP-1-like
      site. Competition studies and antibody supershifts confirmed that the retarded
      complex consists of AP-1-like proteins. pS2-regulated luciferase constructs
      containing mutations specific to the AP-1-like motif greatly diminished the
      inducibility in response to E2. These results suggest that an interaction between
      AhR complexes and AP-1-like proteins may be responsible for TCDD-mediated
      inhibition of E2-induced pS2 expression.

PMID- 9166780
TI  - Partial purification of Pde1 from Saccharomyces cerevisiae: enzymatic redundancy
      for the repair of 3'-terminal DNA lesions and abasic sites in yeast.
AB  - Earlier work indicates that the major DNA repair phosphodiesterase (PDE) in yeast
      cells is the well-characterized Apn1 protein. Apn1 demonstrates both Mg2+
      independent PDE activity and Mg2+-independent class II apurinic/apyrimidinic (AP)
      endonuclease activity and represents greater than 90% of the activity detected in
      crude extracts from wild-type yeast cells. Apn1 is related to Echerichia coli
      endonuclease IV, both in its enzymatic properties and its amino acid sequence. In
      this work, we report the partial purification of a novel yeast protein, Pde1,
      present in Apn1-deficient cells. Pde1 is purified by sequential BioRex-70,
      PBE118, and MonoS chromatography steps using a sensitive and highly specific 3'
      phosphoglycolate-terminated oligonucleotide-based assay as a measure of PDE
      activity. Mg2+-stimulated PDE and Mg2+-stimulated class II AP endonuclease
      copurify during this procedure. These results indicate that yeast, like many
      other organisms studied to date, has enzymatic redundancy for the repair of 3'
      blocking groups and abasic sites.

PMID- 9166781
TI  - Type II DNA topoisomerase from Saccharomyces cerevisiae is a stable dimer.
AB  - Type II DNA topoisomerases function as homodimeric enzymes in transiently
      cleaving double-stranded DNA to catalyze unlinking and unknotting reactions. The
      dimeric enzyme creates a DNA double-strand break by forming a covalent attachment
      between an active site tyrosine from each monomer and a 5'-phosphate from each
      strand of DNA. The dimer must be very stable to dissociation or subunit exchange
      when covalently attached to DNA to prevent directly or indirectly catalyzed
      rearrangements of the genome. Past studies have indicated conflicting results for
      the monomer-dimer stability of topoisomerase II in solution. Here, we report
      results from sedimentation equilibrium studies and two different subunit exchange
      assays indicating that purified Saccharomyces cerevisiae DNA topoisomerase II
      exists as a stable dimer in solution, with a Kd estimated to be < or = 10(-11) M.
      This high dimer stability is not detectably altered by a change of ionic strength
      or by the presence of ATP, ADP, or DNA.

PMID- 9166782
TI  - Fluorescence, phosphorescence, and optically detected magnetic resonance studies
      of the nucleic acid association of the nucleocapsid protein of the murine
      leukemia virus.
AB  - Fluorescence, phosphorescence, and optical detection of triplet state magnetic
      resonance (ODMR) are employed to investigate the interaction of p10, the
      nucleocapsid protein of the Moloney murine leukemia virus, with nucleic acids.
      p10 is a 55-amino acid protein containing a single zinc finger motif,
      C26C29H34C39, that includes Y at position 28 and W at position 35. In addition,
      the interactions of a zinc finger peptide, p10-ZF, comprising residues 24-41 of
      p10, and a doubly mutated 24-41 peptide, p10-ZF' in which the positions of Y and
      W are interchanged, also are reported. The measurements focus on the direct
      involvement of the sole W residue in the nucleic acid interaction. Fluorescence
      quenching and salt-back titrations indicate complex formation of p10 with several
      octanucleotides--(dT)8, (dI)8, (dU)7dT, and (5-BrdU)7dT--and with the
      polynucleotides poly(dT) and poly(dI). Poly(dI) binds with the highest affinity.
      Apparent binding constants and salt-back midpoints are reported. Neither p10-ZF
      nor p10-ZF' exhibits significant fluorescence quenching by these DNA substrates.
      Binding of p10-ZF to fluorescent poly(ethenoadenylic acid) was detected with
      greatly reduced affinity relative to p10, but binding of p10-ZF' was
      undetectable. These results are in general agreement with phosphorescence and
      ODMR measurements monitoring W. Addition of poly(I) to p10 leads to a
      phosphorescence red shift, reduction in the zero-field splitting (ZFS) parameters
      D and E, and a significantly reduced phosphorescence lifetime, each consistent
      with aromatic stacking interactions between W and the nucleobases. These effects
      are smaller with p10-ZF and undetectable with p10-ZF'. Poly(U) produces no
      significant changes in the triplet state parameters of W; no stacking
      interactions are observed even for p10. (5-BrdU)7dT yields large phosphorescence
      red shifts in p10 and p10-ZF, and reductions of D, but no significant heavy atom
      effects. These effects probably are due to enhanced local polarizability caused
      by Br, but any stacking interactions in these complexes would exclude van der
      Waals contacts between W and the Br atoms.

PMID- 9166783
TI  - Peptide hydrophobicity controls the activity and selectivity of magainin 2 amide
      in interaction with membranes.
AB  - The magainins are antibacterial peptides from the skin of Xenopus laevis. They
      show a broad range of activity against prokaryotic cells but lyse eukaryotic
      cells poorly. To elucidate the influence of peptide hydrophobicity on membrane
      activity and selectivity, we designed and synthesized analogs of magainin 2 amide
      with slightly varying hydrophobicities but retained hydrophobic moment, peptide
      charge, and angle subtended by the hydrophilic helix region. Circular dichroism
      investigations of the peptides revealed that all peptides investigated adopt an
      alpha-helical conformation when bound to phospholipid vesicles. Dye-releasing
      experiments from vesicles of phosphatidylglycerol (PG) showed that the membrane
      permeabilizing activity of the analogs is not influenced by peptide
      hydrophobicity. In contrast, the permeability-enhancing activity on vesicles
      bearing high amounts of phosphatidylcholine (PC) increases drastically with
      enhanced peptide hydrophobicity, resulting in a reduced selectivity of more
      hydrophobic analogs for negatively charged membranes. Likewise, the peptide
      affinity to PC-rich membranes increases in the order of hydrophobicity.
      Correlation of peptide binding and membrane permeabilization of PC/PG (3:1)
      vesicles revealed that the observed differences in peptide activity on membranes
      of low negative surface charge are mainly caused by the different binding
      affinities. The antibacterial and hemolytic activity of the peptides increases
      with enhanced hydrophobicity. A strong correlation was found between the
      hemolytic effect and the bilayer-permeabilizing activity against PC-rich
      vesicles. Whereas the antibacterial specificity of the more hydrophobic analogs
      is retained for Escherichia coli, the specificity for Pseudomonas aeruginosa
      decreases with increasing hydrophobicity.

PMID- 9166784
TI  - Investigation of membrane disruption in the reaction catalyzed by cholesterol
      oxidase.
AB  - Dye leakage experiments were undertaken to investigate the membrane disruption
      properties of cholesterol oxidase. Inspection of the X-ray crystal structures of
      cholesterol oxidase suggested that an active-site "lid" opens in order to bind
      substrate [Li, J., Vrielink, A., Brick, P., & Blow, D. M. (1993) Biochemistry 32,
      11507-11515]. We tested whether the interaction of the putative active-site lid
      with the membrane was sufficiently disruptive of the membrane structure to cause
      leakage or lysis of the cell membrane. Vesicles (100 nm) composed of egg
      phosphatidylcholine, 2-palmitoyl-3-oleoyl-1-sn-phosphatidylethanolamine, and 2
      palmitoyl-3-oleoyl-1-sn-phosphatidylcholine were used in this study to mimic
      biomembranes. To separate the effects of membrane binding from conversion of
      cholesterol to cholest-4-en-3-one, the active-site mutant E361Q was utilized. In
      the reaction catalyzed by E361Q, isomerization of the cholest-5-en-3-one
      intermediate is suppressed and cholest-5-en-3-one is the major product isolated.
      Furthermore, E361Q produces cholest-5-en-3-one 20-fold more slowly than wild type
      produces cholest-4-en-3-one from cholesterol. Wild-type and E361Q cholesterol
      oxidases bind to vesicles with an apparent K(D) of approximately 25 microM, as
      measured by quenching of intrinsic tryptophan fluorescence, irrespective of
      headgroup size and cholesterol content. Membrane disruption was measured by
      leakage of the encapsulated marker carboxyfluorescein. Leakage was observed with
      cholesterol-containing vesicles and wild-type enzyme only; the rate of leakage
      was dependent on the rate of cholest-4-en-3-one production. E361Q did not induce
      membrane disruption, regardless of vesicle type tested. Thus, binding of
      cholesterol oxidase to the membrane and partitioning of cholesterol into the
      active site does not sufficiently perturb the bilayer to cause leakage of vesicle
      contents. Formation of the product cholest-4-en-3-one, however, does increase
      membrane permeability. Expansion of the lipid bilayer upon conversion of
      cholesterol to cholest-4-en-3-one is the likely cause of this increased
      permeability.

PMID- 9166785
TI  - Activation of protein kinase C by coexisting diacylglycerol-enriched and
      diacylglycerol-poor lipid domains.
AB  - To test the hypothesis that activation of protein kinase C (PKC) is related to
      the interface between coexisting diacylglycerol- (DAG-) enriched and DAG-poor
      phases, the thermotropic phase behavior of the ternary mixtures
      dimyristoylphosphatidylcholine (DMPC)/dimyristoylphosphatidylserine
      (DMPS)/dioleoylglycerol (DO), DMPC/DMPS/1-palmitoyl-2-oleoylglycerol (PO), and
      DMPC/DMPS/dimyristoylglycerol (DM) was analyzed and compared with the ability of
      the lipid mixtures to support PKC activity. Differential scanning calorimetry
      (DSC) was used to monitor the gel-to-liquid crystalline phase transition as a
      function of the mole fraction of DO (chiDO), PO (chiPO), or DM (chiDM) in
      DMPC/DMPS (1:1) multilamellar vesicles (MLVs) and of chiDO in large unilamellar
      vesicles (LUVs). The addition of DAG at low mole fractions gave rise to the
      appearance of two or more overlapping transitions. The phase boundaries of the
      ternary mixtures deduced from the partial phase diagrams were chiDO =
      approximately 0.10 and approximately 0.3 for DMPC/DMPS/DO, chiPO = approximately
      0.05 and approximately 0.4 for DMPC/DMPS/PO, and chiDM = approximately 0.025 and
      approximately 0.5-0.6 for DMPC/ DMPS/DM. Above these mole fractions of DAG, the
      transitions again became very sharp. The ability of the lipid mixtures to support
      activity of PKC alpha and PKC eta was examined below and above the gel-to-liquid
      crystalline phase transition. In the gel phase, PKC activity went through a
      maximum as a function of increasing mole fraction of each DAG and was restricted
      to lipid compositions in which coexisting phases were observed. Maximal activity
      decreased with increasing saturation of the DAG. In the fluid state, maximal PKC
      activity was shifted to higher DO mole fractions and the peak was much broader.
      Collectively, these data support a role for both the presence and nature of
      interface between compositionally distinct domains in activation of PKC.

PMID- 9166786
TI  - Binding of CTP:phosphocholine cytidylyltransferase to lipid vesicles:
      diacylglycerol and enzyme dephosphorylation increase the affinity for negatively
      charged membranes.
AB  - The regulation of membrane binding and activity of purified CDP:phosphocholine
      cytidylyl-transferase (CT) by lipid activators and enzyme dephosphorylation was
      examined. The binding of CT to membranes was analyzed using sucrose-loaded
      vesicles (SLVs). Binding to phosphatidylcholine vesicles was not detected even at
      a lipid:protein ratio of approximately 2000 (1 mM PC). CT bound to vesicles
      containing anionic lipids with apparent molar partition coefficients between 2 x
      10(5) and 2 x 10(6), depending on the vesicle charge. The vesicle binding and
      activation of CT showed very similar sigmoidal dependencies on the lipid negative
      charge. In addition, diacylglycerol interacted synergistically with anionic
      phospholipids to stimulate both binding and activation at lower mole percent
      anionic lipid. These results demonstrate parallel requirements for binding and
      activity. Dephosphorylation of CT without destabilization was accomplished using
      the catalytic subunit of protein phosphatase 1. Dephosphorylated CT required a
      lower mole percent anionic phospholipid than phosphorylated CT for binding to and
      activation by SLVs. The combination of 10 mol % diacylglycerol and enzyme
      dephosphorylation shifted the mole percent phosphatidic acid required for half
      maximal activation from 25% to 12%. These results suggest a mechanism whereby
      large changes in CT activity can result from changes in the phosphorylation state
      combined with small alterations in the membrane content of diacylglycerol. We
      propose a mechanism whereby dephosphorylation on the domain adjacent to the
      membrane binding domain increases the affinity of the latter for a negatively
      charged membrane surface.

PMID- 9166787
TI  - Identification of amino acid residues that determine the differential ligand
      specificities of folate receptors alpha and beta.
AB  - The homologous folate receptor (FR) types alpha and beta from both human and
      murine sources have opposite stereospecificities for reduced folate coenzymes and
      different affinities for a variety of (anti)folate compounds. The present study
      identifies the critical amino acid sequence divergence underlying functional
      differences between FR-alpha and FR-beta. Chimeric constructs of the cDNAs
      encoding human FR-alpha and FR-beta were expressed in human 293 fibroblasts. The
      resulting membrane associated proteins were characterized in terms of their
      ability to bind [3H]folic acid and their relative affinities for the (6S) and
      (6R) diastereoisomers of N5-methyltetrahydrofolate. Substitution of the amino
      terminal portion (residues 1-92) in the mature FR-alpha polypeptide with the
      corresponding segment of FR-beta resulted in folate binding characteristics
      similar to FR-beta. Next, a series of chimeric constructs were generated,
      involving substitution of progressively shorter segments within residues 1-92 in
      FR-alpha with the corresponding peptides of FR-beta. In this fashion, it was
      determined that the alanine residue at position 49 in FR-alpha was critical for
      its functional divergence from FR-beta, since substitution at this position with
      Leu (the corresponding residue in FR-beta) resulted in the folate binding
      characteristics of FR-beta. Reciprocal substitution in FR-beta with peptide 1-92
      of FR-alpha resulted in poor expression of a [3H]folic acid binding protein. By
      analysis of chimeric constructs, the poor [3H]folic acid binding of the FR
      alpha(1-92)/beta(93-237) chimera could be attributed to interference of a short
      segment from FR-alpha in the vicinity of Ala 49 (peptide 39-59) with proper
      folding of the chimera. Conversion of the ligand binding properties of FR-beta to
      those of FR-alpha required the reciprocal mutation of Leu 49 to Ala, but in
      addition, substitution of one or more residues downstream of amino acid 92 of FR
      beta with the corresponding residues in FR-alpha was essential. The homologous
      murine FR types alpha and beta, which are functionally analogous to the human
      receptor isoforms, also contain a similar Ala vs Leu substitution. These results
      indicate that steric/hydrophobic effects of the side chains of Leu vs Ala at
      position 49 will critically modulate the affinities and stereospecificities of FR
      isoforms for folate compounds. Furthermore, additional amino acid sequence
      divergence at one or more positions downstream of residue 92 in FR-alpha is also
      an essential determinant of the unique functional characteristics of this
      receptor isoform.

PMID- 9166788
TI  - Water and peptide backbone structure in the active center of bovine rhodopsin.
AB  - Difference FTIR spectra in the conversion of rhodopsin or isorhodopsin to
      bathorhodopsin were recorded for recombinant wild-type and E113Q bovine
      rhodopsins. Differences in various vibrational modes between E113Q and the wild
      type proteins whose Schiff bases interact with chloride and Glu113, respectively,
      were analyzed. Water molecules in rhodopsin that change upon formation of
      bathorhodopsin are detected by a change in frequency of the O-H stretching
      vibration from 3538 to 3525 cm(-1). This change in the wild-type protein is
      absent in E113Q. One or a few water molecules are therefore suggested to be
      located in the proximity of Glu113, the counterion of the Schiff base. Another
      water vibration at 3564 cm(-1), which is shifted to 3542 cm(-1) in bathorhodopsin
      in the wild type, persists in E113Q but with approximately 5-cm(-1) shift toward
      higher frequency. This is due to water molecules that may be located at a site
      somewhat more remote from Glu113. Structural changes of some peptide carbonyls
      and amides are also absent in E113Q. On the other hand, the E113Q protein shows
      shifts of the N-H+ stretching vibrational band, that is probably due to the
      protonated Schiff base, upon conversion of rhodopsin to bathorhodopsin. No
      corresponding changes were observed in the wild type. We propose a model in which
      a water molecule interacts with Glu113, the protonated Schiff base, and peptide
      carbonyls, and amides. These residues undergo structural changes upon formation
      of bathorhodopsin.

PMID- 9166789
TI  - Redox dependence for photoligation of manganese to the apo-water-oxidizing
      complex in chloroplasts and photosystem II membranes.
AB  - Effects of reducing reagents and redox potentials on photoactivation were studied
      in Mn-depleted chloroplasts and PSII membranes. Exogenous reducing reagents
      abolished photoactivation in PSII membranes, while they stimulated
      photoactivation in chloroplasts. To determine how reducing reagents can have such
      opposing effects in these preparations, we studied how redox potentials affect
      photoactivation in the range from 0 mV to +500 mV. In chloroplasts, a modest
      yield of photoactivation was obtained in the redox potential range of +100 and
      +330 mV at pH 7.5. The yield of photoactivation decreased at redox potentials
      above +330 mV, and drastically increased below potentials of +100 mV. Nernst
      plots of the data show that an n = 1 redox component with an Em7.5 of +374 mV, as
      well as an n = 2 redox component with an Em7.5 of +61 mV, is involved in
      photoactivation of chloroplasts isolated from dark-grown spruce seedlings. In the
      case of PSII membranes, photoactivation decreased sharply on either side of +335
      mV at pH 5.5. The n = 1 redox components with Em5.5 of +375 and +319 mV may be
      involved, both of which showed pH dependences of -60 mV/pH unit. DCMU abolished
      photoactivation in chloroplasts, but did not affect the dependence of
      photoactivation on oxidation-reduction potentials in PSII membranes. The
      component with an Em5.5 of +319 mV involved in photoactivation of PSII membranes
      was also observed in the dependence of Mn solubilization on oxidation-reduction
      potentials with PSII membranes lacking extrinsic proteins, suggesting that the
      reduction of Mn with higher valences to Mn(II) by exogenous reducing reagents
      reversibly occurs in the intermediates or an active center during photoactivation
      in PSII membranes. Involvement of such redox components in photoactivation in
      chloroplasts and PSII membranes is discussed.

PMID- 9166790
TI  - Synthesis and assembly of the D1 protein into photosystem II: processing of the C
      terminus and identification of the initial assembly partners and complexes during
      photosystem II repair.
AB  - In previous studies [van Wijk, K. J., Bingsmark, S., Aro, E.-M., & Andersson, B.
      (1995) J. Biol. Chem. 270, 25685-25695; van Wijk, K. J., Andersson, B., & Aro, E.
      M. (1996) J. Biol. Chem 271, 9627-9636], we have demonstrated that D1 protein
      synthesized in isolated chloroplasts and thylakoids is incorporated into the
      photosystem II (PSII) core complex. By pulse-chase experiments in these in vitro
      systems, followed by sucrose gradient fractionation of solubilized thylakoid
      membranes, it was shown that this assembly proceeded stepwise; first the D1
      protein was incorporated to form a PSII reaction center complex (PSII rc), and
      through additional assembly steps the PSII core complex was formed. In this
      study, we have analyzed this assembly process in more detail, with special
      emphasis on the initial events, through further purification and analysis of the
      assembly intermediates by nondenaturing Deriphat-PAGE and by flatbed isoelectric
      focusing. The D2 protein was found to be the dominant PSII reaction center
      protein initially associating with the new D1 protein. This strongly suggests
      that the D2 protein is the primary "receptor" or stabilizing component during or
      directly after synthesis of the D1 protein. After formation of the D1-D2
      heterodimer, cyt b559 became attached, whereas the psbI gene product was
      assembled as a subsequent step, thereby forming a PSII reaction center complex.
      Subsequent formation of the PSII core occurred by binding of CP47 and then CP43
      to the PSII rc. The rapid radiolabeling of a minor population of a PSII core
      subcomplex without CP43 indicated that an association of newly synthesized D1
      protein with a preexisting complex consisting of D2/cyt b55q/psbI gene
      product/CP47 was possibly occurring, in parallel to the predominant sequential
      assembly pathway. The kinetics of synthesis and processing of the precursor D1
      protein were followed in isolated chloroplasts and were compared with its
      incorporation into PSII assembly intermediates. No precursor D1 protein was found
      in PSII core complexes, indicating either that incorporation into the PSII core
      complex facilitates the cleavage of the C-terminus or, more likely, that
      processing is more rapid than the assembly into the PSII core.

PMID- 9166791
TI  - Roles of histidine 31 and tryptophan 34 in the structure, self-association, and
      folding of murine interleukin-6.
AB  - Interleukin-6 (IL-6) is a multifunctional cytokine which is involved in a broad
      spectrum of activities such as immune defense, hematopoiesis, and the acute phase
      response, as well as in the pathogenesis of multiple myeloma. A series of murine
      IL-6 (mIL-6) mutants, H31A, W34A, and H31A/W34A, were constructed to investigate
      the roles of His31 and Trp34 in the structure, conformational stability, time
      dependent aggregation, folding, and spectral properties of mIL-6. The
      characteristic pH-dependent quenching of fluorescence of mIL-6 at low pH was
      shown to be caused by an interaction between Trp34 and protonated His31 at low pH
      and not associated with Trp157. Denaturant-induced equilibrium unfolding
      experiments monitored by fluorescence and far-UV CD showed that the increased
      quantum yield and blue shift of the wavelength of the emission maximum observed
      for mIL-6 at moderate denaturant concentrations were also associated with Trp34,
      rather than Trp157. The tendency to form aggregation-prone unfolding
      intermediates, as judged by poor fits to a two-state unfolding mechanism, low m
      values (slopes of the unfolding curve in the transition region), and the range of
      denaturant concentrations over which these intermediates formed, was shown to be
      higher for H31A than mIL-6 but significantly lower for W34A and H31A/W34A. These
      differences were most pronounced at pH 7.4 and correlated with the tendencies of
      the proteins to aggregate at high protein concentrations in the absence of
      denaturant. As judged by the 1H NMR chemical shifts of the aromatic residues, the
      global conformations of H31A and W34A were not significantly different from that
      of mIL-6. Nuclear Overhauser effects (NOE) between the side chains of His31 and
      Trp34 were consistent with the indole side chain of Trp34 being oriented toward
      the face of the imidazolium side chain of His31, an arrangement consistent with
      our estimates of a low interaction energy (0.4-0.6 kcal/mol) between these side
      chains. A shift in the pKa of the His31 side chain in W34A (+0.3 unit) suggested
      that, in the absence of Trp34, His31 could interact with other residues. Further
      mutations in this region should yield forms of mIL-6, even less prone to
      aggregation, which would be more suitable for NMR studies. Mutation of His31 and
      Trp34 to alanine did not significantly alter the mitogenic activity of the
      mutants on mouse hybridoma 7TD1 cells, even though the corresponding region of
      human IL-6 has been shown to be important for biological activity.

PMID- 9166792
TI  - Quaternary structure sensitive tyrosine interactions in hemoglobin: a UV
      resonance Raman study of the double mutant rHb (beta99Asp-->Asn, alpha42Tyr-
      >Asp).
AB  - Two interactions involving tyrosines have been implicated in the communication
      pathway that links ligand binding to quaternary state changes in hemoglobin. Tyr
      alpha(1)42 stabilizes the alpha1beta2 T state interface through the formation of
      a hydrogen bond to Asp beta(2)99. The side chains of the penultimate Tyr residues
      (alpha140 and beta145) occupy the pockets made by helicies F and H in the deoxy
      form with the phenolic hydroxyl hydrogen bonded to the carbonyl group of Val FG5.
      Early crystallographic studies indicated that in the R form the penultimate Tyr
      is expelled out of the pocket, thus eliminating the hydrogen bond. This hydrogen
      bond has been considered to play an important role in maintaining the low-oxygen
      affinity state (T state) in deoxy HbA, but a later higher resolution
      crystallographic study (Shannon, 1983) failed to reveal such movement of this Tyr
      during the R --> T transition. Nevertheless, conversion of this Tyr to Phe
      increases oxygen affinity considerably, suggesting that hydrogen bonding is
      involved in oxygen affinity modulation. Earlier ultraviolet resonance Raman
      results reported by Spiro and co-workers [Rodgers et al. (1992) J. Am. Chem. Soc.
      114, 3697-3709] were used to conclude that the significant quaternary structure
      dependent changes observed in tyrosine Raman bands are due to the formation of
      the T state hydrogen bond with Tyr alpha42 acting as a proton acceptor rather
      than being the anticipated proton donor, as would be expected if Asp beta99 were
      ionized. This surprising result rests on the assumption that changes in the
      environment of Tyr alpha42 are the overwhelming contributor to the R - T UV Raman
      difference spectrum. In this study, a cooperative double mutant lacking Tyr
      alpha42, [rHb (Asp beta99 --> Asn, Tyr alpha42 --> Asp)], is used to determine
      the relative contributions of Tyr alpha42 and the penultimate tyrosines to the R 
      T UV resonance Raman difference spectrum. The results both directly support the
      claim that Tyr alpha42 is the proton acceptor in the T state and expose the
      potential role of the penultimate tyrosines in coupling the quaternary state to
      the ligand reactivity.

PMID- 9166793
TI  - Multifunctional role of Tyr 108 in the catalytic mechanism of human glutathione
      transferase P1-1. Crystallographic and kinetic studies on the Y108F mutant
      enzyme.
AB  - The possible role of the hydroxyl group of Tyr 108 in the catalytic mechanism of
      human glutathione transferase P1-1 has been investigated by means of site
      directed mutagenesis, steady-state kinetic analysis, and crystallographic
      studies. Three representative cosubstrates have been used, i.e. ethacrynic acid,
      7-chloro-4-nitrobenz-2-oxa-1,3-diazole, and 1-chloro-2,4-dinitrobenzene. In the
      presence of ethacrynic acid, the enzyme follows a rapid equilibrium random bi-bi
      mechanism with a rate-limiting step which occurs after the addition of the
      substrates and before the release of products. The replacement of Tyr 108 with
      Phe yields a 14-fold decrease of k(cat), while it does not change appreciably the
      affinity of the H site for the substrate. In this case, it would appear that the
      role of the hydroxyl function is to stabilize the transition state for the
      chemical step, i.e. the Michael addition of GSH to the electrophilic substrate.
      Crystallographic data are compatible with this conclusion showing the hydroxyl
      group of Y108 in hydrogen bonding distance of the ketone moiety of ethacrynic
      acid [Oakley, A. J., Rossjohn, J., Lo Bello, M., Caccuri, A. M., Federici, G., &
      Parker, M. W. (1997) Biochemistry 36, 576-585]. Moreover, no structural
      differences are observed between the Y108F mutant and the wild type, suggesting
      that the removal of the hydroxyl group is solely responsible for the loss of
      activity. A different involvement of Tyr 108 appears in the catalyzed conjugation
      of 7-chloro-4-nitrobenz-2-oxa-1,3-diazole with GSH in which the rate-limiting
      step is of a physical nature, probably a structural transition of the ternary
      complex. The substitution of Tyr 108 yields an approximately 7-fold increase of
      k(cat) and a constant k(cat)/Km(NBD-Cl) value. Lack of a critical hydrogen bond
      between 7-chloro-4-nitrobenz-2-oxa-1,3-diazole and Tyr 108 appears to be the
      basis of the increased k(cat). In the 1-chloro-2,4-dinitrobenzene/GSH system, no
      appreciable changes of kinetics parameters are found in the Y108F mutant. We
      conclude that Y108 has a multifunctional role in glutathione transferase P1-1
      catalysis, depending on the nature of the electrophilic cosubstrate.

PMID- 9166794
TI  - Electrostatic interactions across a beta-sheet.
AB  - The free energy consequences of electrostatic interactions across a model beta
      sheet have been probed using a consensus zinc finger peptide. Relative folding
      free energies have been deduced from coupled peptide folding/metal binding
      reactions. The energies of the electrostatic interactions have been isolated via
      double mutant cycles performed at a series of NaCl concentrations. The observed
      favorable free energies associated with potential ion pairs are modest, less than
      0.5 kcal/mol. Unfavorable interactions due to like-charge pairs of similar
      magnitude were also observed. The largest effects, both favorable and
      unfavorable, involved interactions with aspartic acid. These observations are
      consistent with electrostatic interactions occurring without contact ion pair
      formation with the larger interaction energies involving aspartic acid being due
      to the relative lack of flexibility of its side chain.

PMID- 9166795
TI  - Conditionally lethal Escherichia coli murein mutants contain point defects that
      map to regions conserved among murein and folyl poly-gamma-glutamate ligases:
      identification of a ligase superfamily.
AB  - Bacterial peptidoglycan biosynthesis includes four enzymatic reactions in which
      successive amino acid residues are ligated to uridine diphospho-N-acetylmuramic
      acid (UDP-MurNAc). By comparing the amino acid sequences of MurC, -D, -E, and -F
      proteins from various bacterial genera, four regions of homology were identified.
      A profile search of Swissprot for related sequences revealed that these regional
      similarities were present in the folyl-gamma-polyglutamate ligases. These
      sequence homologies appear to track with catalytic function: both enzyme families
      proceed through an ordered kinetic mechanism and form product via an acyl
      phosphate intermediate. Two highly conserved residues in region II were examined
      through site-directed mutagenesis of the murein D-alanyl-D-alanine-adding enzyme
      from Escherichia coli (murF; E158 and H188). All mutations were highly
      detrimental to activity with enzyme specific activity reductions of 200-4500
      fold, validating the critical nature of these residues. DNA sequence analysis
      from three E. coli mutants harboring the murC3 (G344D), murE1 (G344K, A495S), and
      murF2 (A288T) mutations revealed the presence of point mutation(s) closely
      associated with the fourth of these aligned regions. The murF2 allele, expressed
      and purified as a glutathione S-transferase::MurF2 fusion, was 181-fold less
      catalytically active at 30 degrees C and was further reduced at the nonpermissive
      temperature (42 degrees C). Thus the murF2 temperature-sensitive phenotype arises
      from a point mutation within a highly conserved region within this protein
      family. These data argue that these proteins comprise a superfamily of three
      substrate amide ligases that share significant structural and catalytic
      homologies.

PMID- 9166796
TI  - Two populations of the estrogen receptor separated and characterized using
      aqueous two-phase partitioning.
AB  - Two populations of the rat uterine estrogen receptor (ER) were separated and
      characterized using aqueous two-phase partitioning. Countercurrent distribution
      of rat uterine cytosolic ER allowed rapid and efficient separation of two
      populations, one population partitioned preferentially into the top phase (T,
      K(obs) = 3-6) and the other into the bottom phase (B, K(obs) = 0.01-0.03). The
      majority of unoccupied cytosolic ER is in the T population. Upon estrogen binding
      and/or heating to 30 degrees C in vitro the T population is converted to the B
      population. The transition from T to B does not exclusively involve loss of heat
      shock protein 90 and does not alter the ligand binding ability of the steroid
      binding domain. Using the human ER steroid binding domain overproduced in
      Escherichia coli and the steroid binding domain generated by partial
      trypsinization of the rat uterine ER, we demonstrate that the characteristic
      distinguishing T and B populations is not localized to this domain alone but may
      be associated with the amino terminal half of the ER (the A/B and DNA binding
      domains). The T to B transition of the ER also occurs in human MCF-7 breast
      cancer cells upon treatment with estrogen at 37 degrees C.

PMID- 9166797
TI  - Concentration-dependent inhibitory effects of apolipoprotein E on Alzheimer's
      beta-amyloid fibril formation in vitro.
AB  - Recently, many research groups have examined the effect of apolipoprotein E
      (apoE) on beta-amyloid fibril (betaAf) formation in vitro. However, their data
      were somewhat controversial and no exact kinetic assessment of the role of apoE
      has thus far been available. We examined the effect of human apoE on betaAf
      formation in vitro, starting with various concentrations of freshly prepared beta
      amyloid(1-40) (beta1-40) and using fluorescence spectroscopy with thioflavine T.
      When 50 microM of beta1-40 was incubated with a 1:1000 to 1:100 molar ratio of
      apoE, a dose-dependent inhibitory effect of apoE was observed. Both the
      nucleation and extension phases of betaAf formation in vitro were inhibited by
      apoE. On the other hand, when 300 microM of beta1-40 was incubated with a 1:100
      molar ratio of apoE, the inhibitory effect of apoE was completely abolished. We
      then focused our study on the kinetics of the inhibitory effect of apoE on the
      extension phase of betaAf formation in vitro, utilizing the recently established
      first-order kinetic model of betaAf extension in vitro [Naiki, H., & Nakakuki, K.
      (1996) Lab. Invest. 74, 374-383]. The mathematical treatment of the data suggests
      that apoE inhibits the extension of betaAf in vitro, by making a complex with
      beta1-40, thus eliminating free beta1-40 from the reaction mixture. The
      equilibrium association constant with beta1-40 was practically the same among the
      three major recombinant apoE isoforms. These results indicate that the effects of
      apoE on betaAf formation in vitro is differential and could settle some of the
      controversy about beta-amyloid-apoE interaction in vitro.

PMID- 9166798
TI  - Prenatal ultrasound characterization of the suprarenal mass: distinction between
      neuroblastoma and subdiaphragmatic extralobar pulmonary sequestration.
AB  - With the increased routine use of prenatal ultrasonography, subdiaphragmatic
      masses in the fetus are identified more frequently. Suprarenal masses often are
      presumed to be neuroblastoma and are removed surgically postnatally. We sought to
      better understand the natural history of subdiaphragmatic extralobar pulmonary
      sequestration, and to determine if subdiaphragmatic extralobar pulmonary
      sequestration can be distinguished preoperatively from neuroblastoma. The
      literature was reviewed for cases of prenatally diagnosed suprarenal masses that
      proved ultimately to be either subdiaphragmatic extralobar pulmonary
      sequestration or neuroblastoma. The distinguishing features of the two lesions
      were identified and an algorithm was created on the basis of these distinctions.
      Prenatally diagnosed subdiaphragmatic extralobar pulmonary sequestration is no
      longer rare, with one case being reported for every 2.5 cases of neuroblastoma.
      On prenatal ultrasonography subdiaphragmatic extralobar pulmonary sequestration
      usually is echogenic, is left-sided, and can be identified in the second
      trimester. Neuroblastoma is most often cystic, right-sided, and identified in the
      third trimester. In summary, subdiaphragmatic extralobar pulmonary sequestration
      must be considered in the differential diagnosis of the suprarenal mass
      identified on prenatal ultrasonography. Using the algorithm which we propose, the
      correct diagnosis can be determined prenatally in 95% of patients.

PMID- 9166799
TI  - Doppler ultrasonographic evaluation of blood flow in the superior mesenteric
      artery in celiac patients and in healthy controls in fasting conditions and after
      saccharose ingestion.
AB  - We studied, by means of Doppler ultrasonography, the blood flow in the superior
      mesenteric artery in 12 untreated patients with celiac disease (nontropical
      sprue) and in 15 healthy controls; peak systolic velocity, end diastolic
      velocity, mean velocity, flow volume, and resistive index were measured in the
      fasting state and at regular intervals after ingestion of 0.5 liter of water
      containing 50 g of saccharose. Under fasting conditions, celiac patients showed
      peak systolic velocity, end diastolic velocity, mean velocity, and flow volume
      values significantly higher than those of normal subjects, whereas resistive
      index was significantly lower. After saccharose ingestion these parameters showed
      greater variations in normal subjects than in celiac patients. Fasting end
      diastolic velocity turned out to be the best parameter to distinguish celiac
      patients from healthy subjects. Doppler ultrasonography of the superior
      mesenteric artery could discriminate between normal subjects and celiac patients
      with overt disease. However, these data need further confirmation given the
      limited sample that we studied; moreover, the capability of this technique in
      distinguishing nontropical sprue from other gastrointestinal diseases that cause
      increasing splanchnic flow remains to be ascertained.

PMID- 9166800
TI  - Ventricular discrepancy as a sonographic sign of coarctation of the fetal aorta:
      how reliable is it?
AB  - The purpose of this study was to assess the predictive value and sensitivity of
      discrepant ventricular size for fetal aortic coarctation. Postnatal follow-up
      data were obtained in 42 fetuses in whom ventricular size discrepancy (left
      ventricle smaller than right ventricle) was recognized on an obstetrical
      sonogram. Additionally, from postnatal records, we identified infants with
      coarctation who had had an obstetrical sonogram after 16 weeks. Fourteen of the
      42 fetuses had coarctation or other aortic arch obstruction after birth (33%
      positive predictive value). Eight (62%) of 13 fetuses with ventricular
      discrepancy recognized before 34 weeks had coarctation, compared with six (21%)
      true positive cases among 29 recognized after 34 weeks (P = 0.01, Fisher's exact
      test). Of 21 infants with coarctation, ventricular discrepancy had been
      recognized by prenatal sonography in 13 (62% sensitivity). Ventricular
      discrepancy has moderate sensitivity and mediocre positive predictive value for
      coarctation. The limitations of this finding for diagnosing coarctation,
      particularly a higher false positive rate after 34 weeks, must be recognized, but
      it is still a useful sign to identify this potentially ductus-dependent lesion.

PMID- 9166801
TI  - First trimester isolated fetal nuchal lucency: significance and outcome.
AB  - In this study, we determined the outcome in cases of isolated nuchal lucency seen
      sonographically in the first trimester in fetuses without karyotypic
      abnormalities. We reviewed all cases of isolated localized fetal nuchal lucency
      (3 mm or greater) in 9 to 14 week fetuses over a 4 year period. Fetuses with
      additional sonographic abnormalities were excluded. The width of the nuchal
      lucency at initial sonogram as well as findings on subsequent scans were
      tabulated. Karyotypic, pathologic, and clinical follow-up data were obtained. Of
      44 fetuses with an isolated, localized first trimester nuchal lucency, one was
      lost to follow-up and two were excluded owing to pregnancy termination without
      karyotype or pathologic analysis, thus resulting in 41 fetuses in our study
      group. Five fetuses (12%) had abnormal karyotypes. Twenty-seven of the remaining
      36 fetuses had normal karyotypes, eight others showed no evidence of aneuploidy
      at birth, and one patient underwent spontaneous abortion prior to a karyotypic
      analysis. Among the 36 fetuses without evidence of aneuploidy, six had a poor
      outcome: two were spontaneous abortions, one was a therapeutic abortion of a
      fetus with hydrops and a pericardial effusion seen on fetopsy; one fetus died at
      birth of pulmonary hypoplasia associated with autosomal recessive polycystic
      kidney disease, and one fetus each had Noonan syndrome, and Joubert syndrome. In
      addition, three patients delivered their infants prematurely. Overall, 32 of 41
      fetuses survived, and two (6%) were abnormal. Excluding premature infants, 27
      were normally grown, term survivors. We conclude that other than having an
      increased risk for aneuploidy, fetuses with isolated nuchal lucency are also at
      risk for spontaneous miscarriage, premature delivery, and congenital anomalies
      unassociated with an abnormal karyotype.

PMID- 9166802
TI  - In vivo detection of carotid plaque thrombus by ultrasonic tissue
      characterization.
AB  - The purpose of the study was to determine whether ultrasonic tissue
      characterization could detect carotid plaque thrombus in vivo. Patients
      undergoing carotid endarterectomy were examined preoperatively and the ultrasonic
      tissue characterization findings were compared to those of optical microscopy of
      the removed plaque specimens. Ten of 15 patients studied had plaque thrombus.
      Ultra-ultrasonic tissue characterization entailed an analysis of parameters
      obtained from the power spectrum of backscattered ultrasound signals. Data were
      obtained with a nominal 10 MHz sector scanning transducer with an effective
      bandwidth of 3 to 13 MHz. The parameters were the slope and intercept derived
      from the linear regression of the normalized spectrum and total power (log of the
      integrated power of the normalized spectrum over the effective bandwidth). The
      combined effect of the three parameters was determined by discriminant function
      analysis and showed a significant difference (P < 0.05) between nonthrombus and
      plaque thrombus in a small sample of patients with advance carotid
      atherosclerosis. These parameters applied singly could not provide such a
      distinction. Correct classification of carotid plaque thrombus using the multiple
      parameter analysis revealed a sensitivity of 90%, specificity of 80%, and
      accuracy of 86.7%. This study demonstrates that analysis utilizing a combination
      of multiple spectral parameters was able to detect carotid plaque thrombus in
      vivo.

PMID- 9166803
TI  - Thrombosis of the proximal greater saphenous vein: ultrasonographic diagnosis and
      clinical significance.
AB  - Eleven of 985 (1.1%) patients referred for leg ultrasonographic examinations to
      evaluate for deep venous thrombosis over a 3 year period were found to have
      isolated proximal greater saphenous vein thrombosis. Retrospective review of
      their treatments and sequelae showed that six patients (55%) initially treated
      with anticoagulant medication or high vein ligation had no further sequelae. Of
      four patients (36%) not initially treated, two subsequently developed pulmonary
      embolus, one had clot propagation into the common femoral vein, and one developed
      noncontiguous deep venous thrombosis. The findings of this review would suggest
      aggressive treatment for isolated upper greater saphenous vein thrombosis.

PMID- 9166804
TI  - Improved system for sonographic imaging and biometry of the cornea.
AB  - We developed a programmable motion system for high-frequency (50 MHz)
      ultrasonographic imaging of the cornea. The system permits a variety of scanning
      modes, including arc scans matched to the approximate radius of curvature of the
      cornea. This approach allows high-precision biometry (+ or - 2 microm) over a
      much larger region of the cornea than the 3 mm central zone obtainable with
      conventional rectilinear scanning. Using 60 degree wide meridional arc scans
      covering each clock-hour of a rabbit cornea, we obtained data over an 8 mm wide
      central zone and produced maps representing the thickness of the corneal
      epithelium.

PMID- 9166805
TI  - Postoperative color Doppler flow ultrasonographic assessment of ureteral patency
      in gynecologic oncology patients.
AB  - Our objective was to assess postoperative ureteral patency in gynecologic
      oncology patients with color Doppler flow ultrasonographic assessment of ureteral
      jets. Forty-five consecutive gynecologic oncology patients meeting inclusion
      criteria prospectively underwent postoperative transabdominal color Doppler flow
      ultrasonographic assessment of ureteral jets to establish patency; 48 consecutive
      women undergoing transabdominal ultrasonographic studies for benign gynecologic
      conditions served as a control group. Statistical analysis included two-tailed t
      test, with P < 0.05 considered significant. Bilateral ureteral jets were
      successfully demonstrated by color Doppler flow ultrasonography in all study
      patients and control patients. The mean time required to visualize bilateral
      ureteral jets was significantly different between the study group and control
      group (mean, 5.8 min +/- 0.6 min versus 2.6 min +/- 0.2 min, respectively) (P <
      0.05). We conclude that postoperative ureteral patency in gynecologic oncology
      patients can be easily demonstrated by transabdominal color Doppler flow
      ultrasonographic assessment of ureteric jets.

PMID- 9166806
TI  - Color flow sonography in evaluating the resectability of periampullary and
      pancreatic tumors.
AB  - Over the past several years, we have developed a technique to assess the
      resectability of periampullary and pancreatic tumors using color flow sonography.
      This is a feasibility study to determine if sonography with color flow imaging
      can play a role in evaluating patients with periampullary and pancreatic tumors.
      This study comprises a retrospective analysis of 51 patients referred for color
      flow sonographic evaluation of resectability of periampullary and pancreatic
      neoplasm. Scanning was performed with state-of-the-art color flow sonographic
      systems. Vessels that were touched or occluded by tumor were categorized
      according to a Pancreatic Color Doppler Score. Other factors affecting
      resectability (metastasis, enlarged nodes) were recorded. Sonographic findings
      were correlated with surgical resectability and pathologic findings regarding
      tumor margins. The color flow study was complete technically (all index vessels
      visualized) in 49 of 51 patients (96%). In all, 643 of 647 vessels (99.4%) were
      imaged. Forty-five patients had sufficient surgical, pathologic, or clinical
      proof to be included in the resectability analysis. All 18 patients with
      circumferential tumor or vascular occlusion (Pancreatic Color Doppler Score 4 and
      5) were found to have unresectable disease. All 10 patients in whom tumor did not
      touch (Pancreatic Color Doppler Score 0) had negative margins. All 30 patients
      considered to have unresectable tumors sonographically could not be resected.
      Patients in this category had one or more of the following: positive pathologic
      margins, positive nodes, liver metastasis, or not clinically resectable. Six of
      15 considered resectable sonographically (40%) were unresectable for cure.
      Surgeons believed that color flow sonography influenced management in 10 of 45
      patients (22% overall). Color flow sonography, a painless, noninvasive, and
      relatively inexpensive examination, may be an effective screening tool to
      evaluate periampullary and pancreatic neoplasms for resectability. Our data show
      that color flow sonography can correctly predict unresectability of periampullary
      and pancreatic neoplasms. Any future evaluation of imaging and management of
      periampullary and pancreatic tumors should include color flow sonography.

PMID- 9166807
TI  - Factors related to detection of blood flow by color Doppler ultrasonography in
      intussusception.
AB  - Color Doppler ultrasonography was performed in 125 patients with 134
      intussusceptions. Color flow was present in 121 cases of intussusception (group
      A) and was absent in 13 cases (group B). Young age and duration of symptoms
      greater than 48 hr were significantly related to the nonvisualization of blood
      flow detected by color Doppler sonography (P < 0.05). The successful rate of air
      reduction was significantly higher in group A than in group B (109 of 121 versus
      4 of 13). Color Doppler ultrasonography is useful to predict the reducibility of
      an intussuscepted intestine. The nonvisualization of blood flow by this method is
      not a contraindication for air reduction.

PMID- 9166808
TI  - Lactating adenoma of the breast: antepartum and postpartum sonographic and color
      Doppler imaging appearances with histopathologic correlation.

PMID- 9166809
TI  - Extrarenal Wilms tumor.

PMID- 9166810
TI  - Successful thoracoamniotic shunting and review of the literature in unilateral
      pleural effusion with hydrops.

PMID- 9166811
TI  - Sonographic features of benign papillary neoplasms of the breast: review of 22
      patients.
AB  - The sonographic features of 22 patients with histologically benign intraductal
      papillomas are presented, with clinical, mammographic, galactographic, and
      histopathologic correlation. The most common presenting feature in this series is
      a palpable central breast mass in an elderly woman. Sonography was abnormal in
      all 22 patients. The typical sonographic features include a well-defined, smooth
      walled, solid, hypoechoic nodule or a lobulated, smooth-walled, cystic lesion
      with solid components. Dilated ducts are a common feature, often with visible
      solid intraluminal echoes. These findings suggest the diagnosis of an intraductal
      papilloma. The differential diagnosis includes fibroadenoma and phyllodes tumor
      (for large solid lesions) and intracystic carcinoma (for complex cystic lesions).
      Mammograms are frequently normal (36% of patients). When abnormal, the
      mammographic features are of a smooth-walled, well-defined mass or increased
      retroareolar opacity. Contrary to the reported literature, calcification was seen
      infrequently. We conclude that ultrasonography is useful in the detection and
      delineation of intraductal papillomas.

PMID- 9166812
TI  - Maternal postural challenge as a functional test for cervical incompetence.
AB  - We studied the effect of an upright maternal position on the cervix. Of 41 high
      risk patients (17 to 33 weeks' gestational age), 14 of 16 who had a greater than
      33% decrease in cervical length in the upright position compared to supine
      position delivered their infants prematurely, compared to 1 of 25 patients who
      had a decrease of less than 33% (P < 0.0005). No change in the cervical length
      was noted in 24 low-risk patients, all of whom were delivered at term. When the
      finding of a cervical length of less than 2 cm was combined with a postural
      change, the sensitivity for prediction of preterm delivery was 100%. We conclude
      that for patients at high risk for incompetent cervix, maternal posture-related
      cervical shortening can assist in predicting those who will undergo premature
      delivery.

PMID- 9166813
TI  - Application of automatic boundary detection for computerized quantitative
      analysis of left ventricular regional wall motion by two-dimensional
      echocardiography.
AB  - This study was designed to set up a computer-aided image processing algorithm for
      boundary detection from two-dimensional echocardiography and to establish a
      computerized model for quantitative analysis of left ventricular wall motion with
      the application of automatic boundary detection. The four-chamber view
      echocardiographic images of seven normal subjects and five patients with acute
      myocardial infarction were investigated. The main steps of image processing in
      this algorithm included automatic threshold estimation, contrast stretching,
      radial search of endocardial boundary, and smoothing of the boundary. The
      displacements of the left ventricular endocardial contour from end-diastolic to
      end-systolic frame were measured using a sample point connection model. For
      analysis of the regional contraction, the left ventricular endocardial contour
      was divided equally into six segments. The wall motion curves in patients were
      compared with the normal wall motion pattern established from the normal subjects
      to identify the segments with normal or abnormal wall motion. The results of this
      quantitative method were compared with those of qualitative analysis. In the 30
      segments of the five patients, quantitative analysis correctly identified nine of
      the 11 segments with abnormal wall motion diagnosed by qualitative analysis
      (sensitivity, 82%) and identified 17 of the 19 segments with normal wall motion
      (specificity, 89%). The positive and negative predictive values of quantitative
      analysis were 82% (9 of 11) and 89% (17 of 19), respectively, and the diagnostic
      accuracy was 87% (26 of 30). Our preliminary results suggest that computer-aided
      boundary detection can be applied to establish an objective and useful model for
      quantitative analysis of left ventricular regional wall motion.

PMID- 9166814
TI  - Spigelian hernia: diagnosis by high-resolution real-time sonography.
AB  - The purpose of this study was to demonstrate the role of high-resolution real
      time sonography in the diagnosis of spigelian hernias. The sonographic findings
      in three patients, two of whom had surgical confirmation, are presented. We also
      discuss and demonstrate the anatomic and pathologic factors that predispose to
      these hernias. In all three cases, real-time high-resolution sonography was very
      helpful in providing detailed images of the abdominal wall defect, the hernial
      sac and contents, and the relationship of the contents to the spigelian fascia
      and the rectus, external oblique, and internal oblique muscles. The role of the
      Valsalva and other provocative maneuvers in demonstrating the "in and out"
      sliding movement of the contents of the hernia also is discussed. Although the
      number of cases in our study is small, we think that this modality may be the
      most effective means for establishing this diagnosis, especially in cases with
      equivocal clinical findings.

PMID- 9166815
TI  - Torsion of the testicular appendages: sonographic appearance.
AB  - Torsion of the testis and torsion of the testicular appendages have similar
      presenting features, namely, acute testicular pain and swelling. The former
      condition requires urgent surgical intervention to save the testis; the latter
      condition can be treated conservatively. Despite the frequency of torsion of the
      appendix testis, which is the most common cause of acute hemiscrotum in the
      child, only occasional references to this entity are found in the radiological
      literature. We describe five cases in which an enlarged, homogeneously echogenic
      appendix testis was seen medial or posterior to the head of the epididymis. All
      cases were accompanied by hydrocele and thickening of the scrotal wall. Among the
      five cases, enlargement of the head of the epididymis was seen in four and
      increased testicular blood flow in two. Scanning in the coronal and transverse
      planes above the testis was useful in locating the enlarged, twisted appendix.

PMID- 9166817
TI  - The changes in intrahepatic portal hemodynamics in early stage hepatic abscesses.

PMID- 9166816
TI  - Transvaginal ultrasonographic assessment of Hyskon or lactated Ringer's solution
      instillation after laparoscopy: randomized, controlled study.
AB  - We sought to evaluate two common fluids placed in the pelvis after pelvic surgery
      for their ability to remain in the pelvis for a time thought adequate for
      prevention of adhesions. Thirteen patients undergoing operative laparoscopy were
      randomized to receive 250 ml 32% dextran 70 (Hyskon), 250 ml lactated Ringer's
      solution, or no fluid (control) at the end of surgery. Serial transvaginal
      ultrasonograms were obtained at 1 hr, 3 hr, 6 hr, 24 hr, 96 hr (4 days), and 168
      hr (7 days) after surgery. Patients were asked about side effects of fluid
      instillation. The volume of lactated Ringer's solution declined rapidly after
      instillation, with no significant difference from control at 24 hr (12 ml versus
      7 ml). The volume of Hyskon did not decline rapidly by 24 hr and remained higher
      than the volume in controls or those receiving lactated Ringer's solution (188
      ml, P = 0.003). Although the volume of Hyskon remained higher than that of
      lactated Ringer's solution or fluid volume in control patients by days 4 and 7,
      this difference did not reach statistical significance (45 ml versus 7 ml and 14
      ml respectively, P = 0.39, on day 4). Patients in all groups noted abdominal
      pain. One patient who received Hyskon developed severe vulvar edema and another
      developed dyspnea. We conclude that the volume of Hyskon in the peritoneal cavity
      after laparoscopy does not decline as rapidly as does that of lactated Ringer's
      solution; however, significant side effects may limit its usefulness.
      Transvaginal ultrasonography is useful in monitoring fluids placed in the pelvis
      for prevention of adhesions.

PMID- 9166818
TI  - Ultrasonographic stress testing of ulnar collateral ligament injuries of the
      thumb.
AB  - We compared ultrasonographic stress test evaluation to clinical examination of
      ulnar collateral ligament injuries to the thumb. The results of the sonographic
      and clinical examinations were compared to either operative findings or clinical
      follow-up results if conservative treatment was elected. Of 25 patients, the
      clinical grade injury was identified correctly in 25 with ultrasonography
      compared to 24 with clinical examination. Of the grade III tears, ultrasonography
      missed two patients with Stener tears and physical examination misidentified or
      missed four patients with Stener tears. These results confirm the experience of
      others that ultrasonography is a useful method to evaluate injury to the ulnar
      collateral ligament of the thumb.

PMID- 9166819
TI  - The presence of endometrial fluid in asymptomatic postmenopausal women is
      associated with clinically relevant cervical stenosis.

PMID- 9166820
TI  - Accuracy of ultrasonography in assessing spleen and liver size in patients with
      Gaucher disease: comparison to computed tomographic measurements.
AB  - A comparison was made between volume measurements of spleen and liver by
      ultrasonography and by computed tomography, the two most common modes of
      assessment of organ size in patients with Gaucher disease, who require frequent
      follow-up measurements. The two measurements showed a high degree of correlation
      within a broad range for both spleen and liver volumes. An algorithm for
      conversion of one measurement to the other was derived for both spleen and liver.

PMID- 9166821
TI  - Detection of vertebrobasilar intracranial stenoses: transcranial Doppler
      sonography versus angiography.
AB  - Vertebrobasilar intracranial stenoses seem to carry a higher risk of brain stem
      ischemia than proximal vertebral artery stenoses. Our aim was to assess the value
      of transcranial Doppler sonography versus angiography in detecting and
      quantifying these intracranial stenoses. All consecutive patients who underwent
      transcranial Doppler sonography prior to angiography from 1989 to 1994 and whose
      sonograms showed a stenosis of greater than 50% of one vertebral artery (21
      cases) or of the basilar artery (eight cases) were included in the study. These
      patients were compared with 60 other consecutive stroke patients studied via
      transcranial Doppler sonography prior to normal vertebrobasilar angiography The
      transcranial Doppler sonographic criteria for stenosis were a peak systolic
      frequency shift greater than 2 KHz. A tight stenosis was identified by this
      pattern combined with direct and reverse low frequencies of high spectrum energy.
      The sensitivity of transcranial Doppler sonography using a peak systolic
      frequency shift in diagnosing stenoses reached 80% and its specificity was 97% if
      only atheromatous stenoses were considered. The main diagnostic failures
      concerned bilateral stenoses or contralateral occlusion, tandem lesions, and
      upper basilar artery stenosis. Transcranial Doppler sonography underestimated the
      degree of stenosis compared to angiography in 55% of the cases. We conclude that
      transcranial Doppler sonography is accurate in recognizing a stenosed vessel in
      the intracranial vertebrobasilar circulation, but if this finding will alter
      therapy, the examination must be complemented by magnetic resonance angiography.

PMID- 9166822
TI  - Prenatal diagnosis of gastric duplication cyst.

PMID- 9166823
TI  - Liver infiltration in systemic mastocytosis: ultrasonographic findings.

PMID- 9166824
TI  - Prenatal evaluation of mesenchymal hamartoma of the liver: gray scale and power
      Doppler sonographic imaging.

PMID- 9166825
TI  - Ureteral duplication anomaly with ectopic intraprostatic insertion.

PMID- 9166826
TI  - Interleukin-11: review of molecular, cell biology, and clinical use.

PMID- 9166827
TI  - A clinical evaluation of the International Lymphoma Study Group classification of
      non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project.
AB  - The recognition of several new types of non-Hodgkin's lymphoma (NHL) in recent
      years has led to proposals for changing lymphoma classifications, including a new
      proposal put forth by the International Lymphoma Study Group (ILSG). However, the
      clinical significance of the new entities and the practical utility of this new
      proposal have not been studied. Therefore, we performed a clinical evaluation of
      the ILSG classification. A cohort of 1,403 cases of NHL was organized at nine
      study sites around the world and consisted of consecutive patients seen between
      1988 and 1990 who were previously untreated. A detailed protocol for histologic
      and clinical analysis was followed at each site, and immunologic characterization
      as to T- or B-cell phenotype was required. Five expert hematopathologists visited
      the sites and each classified each case using the ILSG classification. A
      consensus diagnosis was also reached in each case, and each expert rereviewed a
      20% random sample of the cases. Clinical correlations and survival analyses were
      then performed. A diagnosis of NHL was confirmed in 1,378 (98.2%) of the cases.
      The most common lymphoma types were diffuse large B-cell lymphoma (31%) and
      follicular lymphoma (22%), whereas the new entities comprised 21% of the cases.
      Diagnostic accuracy was at least 85% for most of the major lymphoma types, and
      reproducibility of the diagnosis was 85%. Immunophenotyping improved the
      diagnostic accuracy by 10% to 45% for a number of the major types. The clinical
      features of the new entities were distinctive. Both the histologic types and the
      patient characteristics as defined by the International Prognostic Index
      predicted for patient survival. In conclusion we found that the ILSG
      classification can be readily applied and identifies clinically distinctive types
      of NHL. However, for clinical application, prognostic factors as defined by the
      International Prognostic Index must be combined with the histologic diagnosis for
      appropriate clinical decisions.

PMID- 9166828
TI  - Primitive human hematopoietic cells are enriched in cord blood compared with
      adult bone marrow or mobilized peripheral blood as measured by the quantitative
      in vivo SCID-repopulating cell assay.
AB  - We have previously reported the development of in vivo functional assays for
      primitive human hematopoietic cells based on their ability to repopulate the bone
      marrow (BM) of severe combined immunodeficient (SCID) and nonobese diabetic/SCID
      (NOD/SCID) mice following intravenous transplantation. Accumulated data from gene
      marking and cell purification experiments indicate that the engrafting cells
      (defined as SCID-repopulating cells or SRC) are biologically distinct from and
      more primitive than most cells that can be assayed in vitro. Here we demonstrate
      through limiting dilution analysis that the NOD/SCID xenotransplant model
      provides a quantitative assay for SRC. Using this assay, the frequency of SRC in
      cord blood (CB) was found to be 1 in 9.3 x 10(5) cells. This was significantly
      higher than the frequency of 1 SRC in 3.0 x 10(6) adult BM cells or 1 in 6.0 x
      10(6) mobilized peripheral blood (PB) cells from normal donors. Mice transplanted
      with limiting numbers of SRC were engrafted with both lymphoid and multilineage
      myeloid human cells. This functional assay is currently the only available method
      for quantitative analysis of human hematopoietic cells with repopulating
      capacity. Both CB and mobilized PB are increasingly being used as alternative
      sources of hematopoietic stem cells in allogeneic transplantation. Thus, the
      findings reported here will have important clinical as well as biologic
      implications.

PMID- 9166829
TI  - Human MafG is a functional partner for p45 NF-E2 in activating globin gene
      expression.
AB  - Mammalian globin gene expression is activated through NF-E2 elements recognized
      by basic-leucine zipper proteins of the AP-1 superfamily. The specificity of NF
      E2 DNA binding is determined by several nucleotides adjacent to a core AP-1
      motif, comprising a recognition site for transcription factors of the Maf
      subfamily. Earlier work proposed that p18(MafK) forms a heterodimer with
      hematopoietic-specific protein p45 NF-E2 to activate transcription through NF-E2
      sites. However, there was no direct evidence that p18(MafK) serves this function
      in vivo; in fact, mice lacking p18(MafK) have no phenotype. Here we describe a
      novel cDNA clone that encodes the human homolog of chicken MafG. Human MafG
      heterodimerizes with p45 NF-E2 and binds DNA with specificity identical to that
      of purified NF-E2 DNA binding activity. A tethered heterodimer of p45 and MafG is
      fully functional in supporting expression of alpha- and beta-globin, and in
      promoting erythroid differentiation in CB3, a p45-deficient mouse erythroleukemia
      cell line. These results indicate that human MafG can serve as a functional
      partner for p45 NF-E2, and suggest that the p45/MafG heterodimer plays a role in
      the regulation of erythropoiesis.

PMID- 9166830
TI  - The inv(11)(p15q22) chromosome translocation of de novo and therapy-related
      myeloid malignancies results in fusion of the nucleoporin gene, NUP98, with the
      putative RNA helicase gene, DDX10.
AB  - The inv(11)(p15q22) is a recurrent chromosomal abnormality associated with de
      novo and therapy-related myeloid malignancies. Here we report the molecular
      definition of this chromosomal aberration in four patients. Positional cloning
      showed the consistent rearrangement of the DDX10 gene on chromosome 11q22, which
      encodes a putative RNA helicase. The translocation targets the NUP98 gene on
      11p15, a member of the FG peptide repeat nucleoporin family. In DDX10 and NUP98,
      the inv(11) breakpoints occurred within two introns of each gene and the two
      genes merged in-frame to produce the chimeric transcripts characteristic of this
      translocation. Although two reciprocal chimeric products, NUP98-DDX10 and DDX10
      NUP98, were predicted, only NUP98-DDX10 appears to be implicated in
      tumorigenesis. DDX10 is predicted to be involved in ribosome assembly. NUP98 has
      been identified as a nuclear pore complex protein and a target of chromosomal
      translocation in acute myeloid leukemia through the t(7;11)(p15;p15)
      translocation. The predicted NUP98-DDX10 fusion protein may promote
      leukemogenesis through aberrant nucleoplasmic transport of mRNA or alterations in
      ribosome assembly.

PMID- 9166831
TI  - The t(11;16)(q23;p13) translocation in myelodysplastic syndrome fuses the MLL
      gene to the CBP gene.
AB  - The recurrent translocation t(11;16)(q23;p13) has been reported to be associated
      with therapy-related acute leukemia. The MLL gene involved in other 11q23
      abnormalities was also rearranged by this translocation. We analyzed two patients
      with myelodysplastic syndrome with t(11;16) and showed that the MLL gene on 11q23
      was fused with CREB-binding protein (CBP) gene on 16p13 in these patients. The
      CBP gene encodes a transcriptional adaptor/coactivator protein and it is mutated
      in patients with Rubinstein-Taybi syndrome. The CBP gene is also involved in
      acute myeloid leukemia (AML) with t(8;16)(p11;p13). In-frame MLL-CBP fusion
      transcripts combine the MLL AT-hook motifs and DNA methyltransferase homology
      region with a largely intact CBP. Our results combined with the finding of the
      MOZ-CBP fusion in t(8;16)-AML suggest that the CBP gene may be associated with
      leukemogenesis through translocations.

PMID- 9166832
TI  - Immunotherapy with recombinant human interleukin-2 and recombinant interferon
      alpha in lymphoma patients postautologous marrow or stem cell transplantation.
AB  - Immune-mediated effects appear to play a major role in controlling minimal
      residual disease (MRD). We, therefore, investigated the role of recombinant human
      interleukin-2 (rIL-2) given concomitantly with interferon-alpha (IFN-alpha) in
      malignant lymphoma (ML) patients with responding disease following autologous
      bone marrow or blood stem cell transplantation (ABSCT). Fifty-six patients were
      included in this investigation. Thirty-two patients had non-Hodgkin's lymphoma
      (NHL) and 24 patients had Hodgkin's disease (HD). Sixty-one patients (NHL 36, HD
      25) served as historical controls. Patients from both groups had similar
      demographic characteristics, the same stage of disease at presentation, status of
      disease at transplantation, conditioning regimens, and type of transplant. rIL-2
      and IFN-alpha were self-administered in two cycles beginning 2.5 to 10.5 months
      (median, 4 months) posttransplant and separated by a 4-week interval. Each cycle
      consisted of IFN-alpha subcutaneously (SC) 3 x 10(6) U/d x 5 d/wk combined with
      rIL-2 SC 3 to 6 IU/m2/d x 5 d/wk for 4 weeks. The incidence of survival and
      disease-free survival (DFS) was significantly higher in the group under
      investigation than in the historical controls (P < .01). Of 56 patients with ML
      treated with IFN-alpha + rIL-2, 45 patients are DFS (80.4%) after a follow-up of
      7 to 78 months (median, 34 months), whereas in the historical controls, 32 of 61
      (52.5%) patients are disease free, in a follow-up of 4 to 84 months (median, 23
      months) posttransplant (P < .01). Our preliminary results are encouraging and
      suggest that home administered immunotherapy with IFN-alpha and rIL-2 is
      relatively well tolerated and may intensify remission in ML patients with MRD
      following ABSCT.

PMID- 9166834
TI  - Rapid engraftment without significant graft-versus-host disease after allogeneic
      transplantation of CD34+ selected cells from peripheral blood.
AB  - We have prospectively evaluated the feasibility and results of the biotin-avidin
      immunoadsorption method (Ceprate SC system) for a phase I/II study of T-cell
      depletion of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral
      blood progenitor cells (PBPC) for allogeneic transplantation. Twenty consecutive
      patients, median age, 40 years (21 to 54) and diagnoses of chronic myeloid
      leukemia in chronic phase (n = 5), acute myeloblastic leukemia (n = 7), acute
      lymphoblastic leukemia (n = 2), chronic myelomonocytic leukemia (n = 1),
      refractory anemia with excess of blasts in transformation (n = 3), histiocytosis
      X (n = 1), and chronic lymphocytic leukemia (n = 1), were conditioned with
      cyclophosphamide (120 mg/kg) and total body irradiation (13 Gy; 4 fractions). HLA
      identical sibling donors received G-CSF at 10 microg/kg/d subcutaneously (SC); on
      days 5 and 6 (19 cases) and days 5 to 8 (1 case) donors underwent 10 L
      leukapheresis. PBPC were purified by positive selection of CD34+ cells using
      immunoadsorption biotin-avidin method (Ceprate SC) and were infused in the
      patients as the sole source of progenitor cells. No growth factors were
      administered posttransplant. The median recovery of CD34+ cells after the
      procedure was of 65%. The median number of CD34+ cells infused in the patients
      was 2.9 (range, 1.5 to 8.6) x 10(6)/kg. The median number of CD3+ cells
      administered was 0.42 x 10(6)/kg (range, 0.1 to 2). All patients engrafted.
      Neutrophil counts >500 and >1,000/microL were achieved at a median of 14 days
      (range, 10 to 18) and 15 days (range, 11 to 27), respectively. Likewise, platelet
      counts >20,000 and >50,000/microL were observed at a median of 10 days (range, 6
      to 23) and 17 days (range, 12 to 130), respectively. Graft-versus-host disease
      (GVHD) prophylaxis consisted of cyclosporine plus methylprednisolone. No patient
      developed either grade II to IV acute or extensive chronic GVHD. After a median
      follow-up of 7.5 months (range, 2 to 22) three patients have relapsed, and one of
      them is again in hematologic and cytogenetic remission after infusion of the
      donor lymphocytes. Two patients died in remission: one on day +109 of pulmonary
      aspergillosis and the other on day +251 of metastasic relapse of a previous
      breast cancer. Sixteen of the 20 patients are alive in remission after a median
      follow-up of 7.5 months (range, 2 to 22). In conclusion, despite the small number
      of patients and limited follow-up, it appears that this method allows a high
      CD34+ cell recovery from G-CSF mobilized PBPC and is associated with rapid
      engraftment without significant GVHD, and with low transplant related mortality.

PMID- 9166833
TI  - Prognostic significance of fluorescence intensity of surface marker expression in
      childhood B-precursor acute lymphoblastic leukemia. A Pediatric Oncology Group
      Study.
AB  - This report describes the prognostic significance of the intensity of surface
      membrane antigen expression in a series of 1,231 children older than 1 year with
      newly diagnosed B-precursor acute lymphoblastic leukemia (ALL) treated on
      Pediatric Oncology Group (POG) treatment protocols. All patients had dual-color
      flow cytometric immunophenotyping performed at a central reference laboratory
      with a standard panel of monoclonal antibodies. The flow cytometers used in the
      study were calibrated with a standard fluorescence microparticle that permitted
      conversion of relative fluorescence channels to standard units of mean
      equivalents of soluble fluorochrome (MESF). In univariate analysis, fluorescence
      intensity of CD45 and CD20 was significantly associated with event-free survival
      (EFS), whereas other markers showed no significant correlation with outcome.
      Patients whose blasts were greater than the 75th percentile of intensity for CD45
      (corresponding to 18,000 MESF units with CD45-FITC, or about 8% of the intensity
      of normal lymphocytes) fared significantly worse than those with lower-density
      CD45, and those whose blasts were greater than the 25th percentile of intensity
      for CD20 (corresponding to 17,900 MESF units with CD20-PE) had a poorer EFS. The
      intensity of both CD45 and CD20 was independently correlated with outcome. There
      was no significant correlation between intensity of expression of either antigen
      and traditional clinical risk factors, ploidy, or t(9;22) or t(1;19). All
      patients with t(4;11) had CD45 intensity greater than the 75th percentile, but
      CD45 intensity retained its prognostic significance after adjusting for t(4;11).
      In multivariate analysis, both CD45 intensity greater than the 75th percentile
      and CD20 intensity greater than the 25th percentile were significantly correlated
      with poor outcome independently of previously reported poor prognostic factors
      including National Cancer Institute (NCI) risk group, ploidy, trisomies of 4 and
      10, and adverse translocations including t(1;19), t(9;22), and t(4;11). We
      conclude that in childhood B-precursor ALL, the intensity of expression of CD20
      and CD45 provides prognostic information not available from simple consideration
      of antigen expression as positive or negative, and adds to that obtained from
      traditional clinical and biologic risk factors.

PMID- 9166836
TI  - Polyploidization and functional maturation are two distinct processes during
      megakaryocytic differentiation: involvement of cyclin-dependent kinase inhibitor
      p21 in polyploidization.
AB  - The mechanism of megakaryocytic differentiation was investigated using human
      megakaryocytic leukemia cell line UT-7. Polyploidization of UT-7 cells was
      induced by the microtubule-depolymerizing agent, nocodazole, and 12-O
      tetradecanoylphorbol-13-acetate (TPA), but the effect was much more striking with
      nocodazole. By contrast, induction of cytoplasmic maturation, as judged by beta
      thromboglobulin production and platelet factor 4 expression, was more prominent
      in TPA-treated cells than in nocodazole-treated cells. Nocodazole and TPA could
      act synergistically to increase ploidy and to enhance the expression of mature
      phenotypes. Human thrombopoietin induced functional maturation but not
      polyploidization in UT-7 cells and also acts synergistically with nocodazole.
      Cyclin-dependent kinase inhibitor p21 was upregulated at the early stage of
      megakaryocytic differentiation, and overexpression of p21 resulted in an increase
      in ploidy of UT-7 cells. This suggests that p21 is implicated in polyploidization
      via suppression of CDC2 activity at mitosis. UT-7 but not HL-60 cells could
      incorporate [3H]thymidine in the presence of TPA, indicating the presence of
      megakaryocyte-specific licensing factor to allow DNA replication during
      differentiation. Taking these data together, we propose that megakaryocytic
      differentiation consists of two distinct processes, polyploidization and
      functional maturation, and that these two processes are independently regulated.

PMID- 9166835
TI  - Randomized trial with or without granulocyte colony-stimulating factor as adjunct
      to induction VNCOP-B treatment of elderly high-grade non-Hodgkin's lymphoma.
AB  - Age is an important prognostic parameter, especially in patients with advanced
      high-grade non-Hodgkin's lymphoma (HG-NHL) who require more intensive and
      extensive therapy for any possible chance of cure. We investigated the potential
      of granulocyte colony-stimulating factor (G-CSF) for reducing myelotoxicity,
      which is the most important dose-limiting factor for chemotherapy. Between March
      1993 and June 1995, 158 previously untreated patients 60 years and older with HG
      NHL were included in a cooperative randomized comparative trial and treated with
      a combination therapy including VNCOP-B (cyclophosphamide, mitoxantrone,
      vincristine, etoposide, bleomycin, and prednisone) with or without G-CSF. G-CSF
      was administered at 5 microg/kg/d throughout the treatment starting on day 3 of
      every week for 5 consecutive days. Of the 158 patients registered for the trial,
      149 patients were evaluable: 77 received VNCOP-B plus G-CSF and 72 received VNCOP
      B alone. The overall response rate was 81.5%, with complete response in 59%: 60%
      in the VNCOP-B plus G-CSF group, and 58% in the VNCOP-B group. At 30 months
      (median 24 months), 68% of all complete responders were alive without disease in
      the G-CSF group and 65% in the control group. Neutropenia occurred in 18 out of
      77 (23%) of the G-CSF treated patients and in 40 out of 72 (55.5%) of the
      controls (P = .00005). Clinically relevant infections occurred in 4 out of 77
      (5%) of the G-CSF group and in 15 out of 72 (21%) of the controls (P = .004). The
      delivered dose intensity was higher in patients receiving G-CSF (95% v 85%), but
      the difference was not statistically significant. Our data show that VNCOP-B is a
      feasible and effective regimen in elderly HG-NHL patients, and that the use of G
      CSF reduces infection and neutropenia rates without producing any significant
      modifications to the dose intensity, CR rate, and relapse-free survival curve.

PMID- 9166837
TI  - Primitive long-term culture initiating cells (LTC-ICs) in granulocyte colony
      stimulating factor mobilized peripheral blood progenitor cells have similar
      potential for ex vivo expansion as primitive LTC-ICs in steady state bone marrow.
AB  - We have recently shown that more than 90% of long-term culture initiating cells
      (LTC-IC) mobilized in the peripheral blood (PB) of normal individuals express HLA
      DR and CD38 antigens and can sustain hematopoiesis for only 5 weeks. However, 10%
      of LTC-IC in mobilized PB are CD34+ HLA-DR- and CD34+ CD38- and can sustain
      hematopoiesis for at least 8 weeks. We now examine the ex vivo expansion
      potential of CD34+ HLA-DR+ cells (rich in mature LTC-IC) and CD34+ HLA-DR- cells
      (rich in primitive LTC-IC) in granulocyte colony-stimulating factor (G-CSF)
      mobilized PB progenitor cells (PBPC). Cells were cultured in contact with M2-10B4
      cells (contact) or in transwells above M2-10B4 (noncontact) without and with
      interleukin-3 (IL-3) and macrophage inflammatory protein (MIP-1alpha) for 2 and 5
      weeks. Progeny were evaluated for the presence of colony-forming cells (CFC) and
      LTC-IC. When CD34+ HLA-DR+ PB cells were cultured in contact cultures without
      cytokines, a threefold expansion of CFC was seen at 2 weeks, but an 80% decrease
      in CFC was seen at week 5. Further, the recovery of LTC-IC at week 2 was only 17%
      and 1% at week 5. This confirms our previous observation that although CD34+ HLA
      DR+ mobilized PB cells can initiate long-term cultures, they are relatively
      mature and cannot sustain long-term hematopoiesis. In contrast, when CD34+ HLA-DR
      mobilized PB cells were cultured in contact cultures without cytokines, CFC
      expansion persisted until week 5 and 49% and 11% of LTC-IC were recovered at week
      2 and 5, respectively. As we have shown for steady state bone marrow (BM)
      progenitors, recovery of LTC-IC was threefold higher when CD34+ HLA-DR- PBPC were
      cultured in noncontact rather than contact cultures, and improved further when IL
      3 and MIP-1alpha were added to noncontact cultures (96 +/- 2% maintained at week
      5). We conclude that although G-CSF mobilizes a large population of "mature"
      CD34+ HLA-DR+ LTC-IC with a limited proliferative capacity, primitive CD34+ HLA
      DR- LTC-IC present in mobilized PB have similar characteristics as LTC-IC from
      steady state BM: (1) they can be maintained in noncontact cultures containing IL
      3 and MIP-1alpha for at least 5 weeks; (2) they are subject to the same
      proliferation inhibitory influences of contact with stroma. Since the absolute
      number of primitive LTC-IC (week 8 LTC-IC) per mL of G-CSF mobilized PB is
      similar to that per mL of steady state BM, these studies further confirm that G
      CSF mobilized PBPC may have similar long-term repopulating abilities as steady
      state BM.

PMID- 9166838
TI  - Flt-3 ligand synergizes with granulocyte colony-stimulating factor to increase
      neutrophil numbers and to mobilize peripheral blood stem cells with long-term
      repopulating potential.
AB  - Flt-3 ligand (FL) shares many features with stem cell factor (SCF), a widely
      documented cofactor for peripheral blood progenitor cell (PBPC) mobilization. We
      investigated the mobilization of PBPCs by FL in combination with granulocyte
      colony-stimulating factor (G-CSF). As a single agent, FL was a relatively modest
      mobilizer of PBPCs, resulting in 360 granulocyte/macrophage colony-forming cells
      (GM-CFCs)/mL blood (control, 155 GM-CFCs/mL blood) and no advantage in leukocyte
      recovery when these PBPCs were transplanted to irradiated recipient mice. G-CSF,
      on the other hand, mobilized over 20,000 GM-CFCs/mL blood, and the combination of
      G-CSF + FL resulted in over 100,000 GM-CFCs/mL blood. The combination of G-CSF +
      FL stimulated increased levels of monocytes and basophils in the peripheral
      blood. The performance of the mobilized PBPC product in irradiated hosts
      correlated with progenitor numbers resulting in long-term engraftment in
      association with accelerated short-term recovery of both leukocytes and
      platelets. These data demonstrate the potential of FL to synergize with G-CSF to
      mobilize PBPCs with both short- and long-term engraftment potential. The effect
      is similar to the synergistic interaction of G-CSF and SCF on PBPC mobilization.
      The use of FL as opposed to SCF may elicit a different spectrum of toxicities
      including lymphoid proliferation effects, in contrast to the mast cell
      degranulation effects of SCF. Clinical studies of FL are needed to evaluate its
      usefulness in man.

PMID- 9166839
TI  - Clonal proliferation and cytokine requirement of murine progenitors for natural
      killer cells.
AB  - We have established a clonal cell culture system that supports the proliferation
      of committed natural killer (NK) cell progenitors of mice to investigate the
      pathway and cytokine regulation of NK cell development. Day 14 fetal thymocytes
      cultured in methylcellulose with interleukin-7 (IL-7), IL-15, and steel factor
      (SF) formed diffuse colonies that could not be classified to known colony types.
      Single-cell origin of the colonies was established by micromanipulation of the
      colony-forming cells. Cells in the colonies are very blastic, showing no
      cytoplasmic differentiation, and express Ly5, Thy-1, and CD25 but not myeloid, B,
      mature T, or NK cell markers. The cells lack T, B, and myeloid potentials but can
      differentiate to mature NK cells in fetal thymus organ culture, suggesting that
      the colonies consist of NK committed progenitors. Examination of the minimal
      cytokine requirement for the NK colony formation showed that IL-7 and SF are
      indispensable for the formation of immature NK cell colonies. Both IL-2 and IL-15
      increased the frequency of colonies. In contrast to IL-2, IL-7, and IL-15, IL-4
      strongly inhibited the formation of the colonies. This quantitative clonal
      culture will provide a useful means to examine the mechanism of NK cell
      development.

PMID- 9166840
TI  - Potential and distribution of transplanted hematopoietic stem cells in a
      nonablated mouse model.
AB  - Increasingly, allogeneic and even more often autologous bone marrow transplants
      are being done to correct a wide variety of diseases. In addition, autologous
      marrow transplants potentially provide an opportune means of delivering genes in
      transfected, engrafting stem cells. However, despite its widespread clinical use
      and promising gene therapy applications, relatively little is known about the
      mechanisms of engraftment in marrow transplant recipients. This is especially so
      in the nonablated recipient setting. Our data show that purified lineage negative
      rhodamine 123/Hoechst 33342 dull transplanted hematopoietic stem cells engraft
      into the marrow of nonablated syngeneic recipients. These cells have multilineage
      potential, and maintain a distinct subpopulation with "stem cell"
      characteristics. The data also suggests a spatial localization of stem cell
      "niches" to the endosteal surface, with all donor cells having a high spatial
      affinity to this area. However, the level of stem cell engraftment observed
      following a transplant of "stem cells" was significantly lower than that expected
      following a transplant of the same number of unseparated marrow cells from which
      the purified cells were derived, suggesting the existence of a "nonstem cell
      facilitator population," which is required in a nonablated syngeneic transplant
      setting.

PMID- 9166841
TI  - In vitro development of erythroid and megakaryocytic cells from a UT-7 subline,
      UT-7/GM.
AB  - UT-7 is a human megakaryoblastic leukemia cell line with absolute dependence on
      interleukin-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), or
      erythropoietin (EPO) for growth and survival. We isolated a novel subline, UT
      7/GM after long-term culture of UT-7 with GM-CSF. The hemoglobin concentration
      and gamma-globin and EPO-receptor mRNA levels were significantly higher in EPO
      treated UT-7/GM cells than in untreated cells. In contrast, the platelet factor 4
      and glycoprotein IIb mRNA levels were much higher in thrombopoietin (TPO)-treated
      UT-7/GM cells than in untreated cells. Some TPO-treated cells had morphologically
      mature megakaryocytic characteristics such as a developed demarcation membrane in
      the cytoplasm and multilobular nuclei. These findings indicate that UT-7/GM is a
      bipotential cell line that can be induced to differentiate into erythroid and
      megakaryocytic lineages by EPO and TPO, respectively. Moreover, a minority of UT
      7/GM cells acquired a high hemoglobin concentration by treatment with TPO,
      suggesting that TPO in part induced the erythroid differentiation of the UT-7/GM
      cells. Interestingly, GM-CSF inhibited the EPO- or TPO-induced erythroid
      differentiation and the TPO-induced megakaryocytic differentiation of UT-7/GM
      cells. These results support the hypothesis that cytokines influence the
      programming of gene expression required for lineage commitment or
      differentiation.

PMID- 9166842
TI  - Low drug attributability of aplastic anemia in Thailand. The Aplastic Anemia
      Study Group.
AB  - From 1989 to 1994, a population-based, case-control study of aplastic anemia was
      conducted in Thailand, including the regions of Bangkok, Khonkaen in the
      northeast, and Songkla in the south. An annual incidence in Bangkok of 3.7 cases
      per million population, about twice as high as in Western countries, has been
      reported. To evaluate the etiologic role of drugs, 253 subjects were compared
      with 1,174 hospital controls. With multivariate adjustment for confounding, a
      significant association was identified for exposure 2 to 6 months before
      admission to thiazide diuretics (relative risk estimate 7.7; 1.5 to 40). There
      were crude associations with sulfonamides (relative risk estimate, 7.9; P =
      0.004) and mebendazole (6.3; P = 0.03) (there were insufficient data for
      multivariate adjustment). Excess risks for the three drugs were in the range of 9
      to 12 cases per million users. There was no significant association with
      chloramphenicol, although the multivariate relative-risk estimate was elevated
      (2.7; 0.7 to 10). Other drugs that have been reported to increase the risk of
      aplastic anemia, such as nonsteroidal anti-inflammatory drugs and
      anticonvulsants, were not commonly used. There were no associations with commonly
      used drugs, including benzodiazepines, antihistamines, oral contraceptives, and
      herbal preparations. For all associated drugs, the overall etiologic fraction
      (the proportion of cases attributable to an exposure) was 5%, compared with 25%
      in Europe and Israel. Drugs are uncommon causes of aplastic anemia in Thailand,
      and their use does not explain the relatively high incidence of the disease in
      that country.

PMID- 9166844
TI  - Platelet and megakaryocyte dense granules contain glycoproteins Ib and IIb-IIIa.
AB  - Platelets contain two main types of secretory organelles, the dense granules and
      the alpha-granules. P-selectin, a specific receptor for leukocytes that is
      present in the alpha-granule membrane, has also been demonstrated to be
      associated with the dense granule limiting membrane, showing that a relationship
      exists between these two types of secretory granules. We have previously shown
      that the plasma membrane receptors glycoproteins (Gp) IIb-IIIa and Ib are also
      present in the alpha-granule membrane. To document further the composition of the
      dense granule membrane, we have used immunoelectron microscopy in the present
      work to determine if the dense granule membrane also contains these
      glycoproteins. First, the cytochemical method of Richards and Da Prada (J
      Histochem Cytochem 25:1322, 1977), which specifically enhances dense body
      electron density, was combined with immunogold-labeled anti-Gp IIb-IIIa or anti
      Gp Ib antibody. A consistent and reproducible labeling for Gp IIb-IIIa, but less
      for Gp Ib, was found in the membrane of platelet dense granules. Subsequently,
      double immunogold labeling was performed on frozen thin sections of resting
      platelets using antibodies directed against the dense body components
      granulophysin or P-selectin, followed by anti-Gp IIb-IIIa or anti-Gp Ib.
      Consistent labeling for Gp IIb-IIIa and weaker labeling for Gp Ib were detected
      in dense bodies. The possibility that the granulophysin-positive structures could
      be lysosomes was excluded by the presence of P-selectin. Immunogold labeling of
      isolated dense granule fractions confirmed these results. Identical findings were
      made on human cultured megakaryocytes using double immunolabeling. In conclusion,
      this study demonstrates the presence of Gp IIb-IIIa and Gp Ib on the dense
      granule membrane. This observation provides additional evidence of similarities
      between the alpha-granule and dense granule membranes and raises the possibility
      of a dual mechanism responsible for the formation of dense granules similar to
      that of alpha-granules, ie, endogenous synthesis as well as endocytosis from the
      plasma membrane.

PMID- 9166843
TI  - Retroviral gene transduction of adult peripheral blood or marrow-derived CD34+
      cells for six hours without growth factors or on autologous stroma does not
      improve marking efficiency assessed in vivo.
AB  - Our previous work in patients undergoing autologous transplant for multiple
      myeloma (MM) or breast cancer (BC) has shown that retroviral transduction of
      adult CD34+ cells for 72 hours in the presence of interleukin-3 (IL-3), IL-6, and
      stem cell factor (SCF) resulted in .01% to 1% long-term marking of peripheral
      blood and marrow cells (Blood 85:3948, 1995). In this study we compare these
      previous studies to transduction with no added growth factors, previously shown
      to result in higher levels of marking in children (Lancet 342:1134, 1993) or
      transduction in the presence of an autologous stromal layer. Peripheral blood
      (PB) mononuclear cells were collected via apheresis after high-dose
      cyclophosphamide and granulocyte colony-stimulating factor. Bone marrow (BM) was
      also harvested in all patients. One third of both BM and PB collections were
      enriched for CD34+ cells and transduced with one of two marking vectors
      containing the neomycin-resistance gene to distinguish cells originating from BM
      and PB posttransplantation. Cells from 3 MM and 2 BC patients were transduced
      without growth factors for 6 hours and cells from 2 MM and 2 BC patients were
      transduced in the presence of autologous marrow stroma. Immediately
      posttransduction, the percentage of Neo-resistant PB and BM progenitors (colony
      forming units) were: 0% to 19% in the 6-hour no growth factor group and 0% to 36%
      in the autologous stroma group. After conditioning therapy, both transduced and
      untransduced PB and BM fractions were infused into the patients. Semi
      quantitative nested DNA polymerase chain reaction was performed on total,
      mononuclear, and granulocyte fractions of PB and BM at 1, 3, 6, 9, 12, and 18
      months. Poor marking has been observed in both groups, with no consistently
      positive patients. These results compare unfavorably with our prior experience
      using growth factors during transduction. Further optimization of transduction
      conditions and vectors needs to be developed to improve transduction efficiency
      of adult human repopulating hematopoietic cells.

PMID- 9166845
TI  - Genomic sequence and transcription start site for the human gamma-glutamyl
      carboxylase.
AB  - The human gene for gamma-glutamyl carboxylase is 13 kb in length and contains 15
      exons. Transcription starts at a cytosine 217 base pair upstream of the first
      codon. There are two major transcripts in all tissues examined. They are
      distinguished by the presence of an Alu sequence in the 3' nontranslated end of
      the longer species. Relative mRNA levels for 12 bovine tissues are presented.

PMID- 9166846
TI  - Metabolism of thrombopoietin (TPO) in vivo: determination of the binding dynamics
      for TPO in mice.
AB  - Previous in vivo studies have established that plasma thrombopoietin (TPO) levels
      are regulated by binding to c-Mpl on platelets and that, in vitro, platelets bind
      and degrade TPO. To determine if the in vivo metabolism of TPO was specific and
      saturable, we injected normal CD-1 mice IV with trace amounts of 125I-rmTPO with
      or without a saturating concentration of rmTPO. The amount of radioactivity
      present in the spleen, blood cell fraction, platelet fraction, tibia/fibula, and
      femur was significantly greater in the mice receiving 125I-rmTPO alone.
      Conversely, the amount of radioactivity present in the plasma was significantly
      greater in the mice receiving both 125I-rmTPO and rmTPO, thus suggesting the
      uptake of rmTPO by the spleen, platelets, and bone marrow in vivo was saturable.
      Platelet and spleen homogenates from animals receiving 125I-rmTPO alone showed a
      degradation pattern of 125I-rmTPO similar to that observed in vitro using mouse
      platelet rich plasma. To determine the in vivo binding dynamics for rmTPO, mice
      were injected with 125I-rmTPO alone or with increasing concentrations of rmTPO;
      spleen and blood cell-associated radioactivity was determined at 2 hours
      postinjection. A 4-parameter curve fit of the data indicated that the "in vivo
      binding affinity" for rmTPO was approximately 6.4 microg/kg. These data indicate
      that after a dose of approximately 6.4 microg/kg, 50% of all c-Mpl receptors will
      be saturated with rmTPO. Electron microscopy indicated that radioactivity was
      present bound to and within megakaryocytes and platelets in both sternum and
      spleen and platelets in circulation. Together these data demonstrate that in
      vivo, 125I-rmTPO is mainly metabolized by platelets and to a small extent by
      cells of the megakaryocyte lineage, via a specific and saturable mechanism.

PMID- 9166847
TI  - Cytokine treatment of endothelial cells increases glycoprotein Ib alpha-dependent
      adhesion to von Willebrand factor.
AB  - Endothelial cells (EC) possess at least two membrane receptors for von Willebrand
      factor (vWF), the vitronectin receptor (VNR, alpha(v)beta3), which recognizes an
      Arg-Gly-Asp (RGD) sequence in the C-terminus of vWF, and glycoprotein Ib alpha
      (GP Ib alpha), which interacts with a region in the N-terminal A1 domain of vWF.
      In the absence of added cytokines, EC attachment to a vWF substratum is mediated
      largely through the alpha(v)beta3, with a smaller contribution by GP Ib alpha. In
      the present study, we have examined the effect of cytokines on the receptor
      specificity of EC attachment to wild-type vWF (WT-vWF) and to vWF, which had been
      mutated in the C-terminal RGDS sequence (RADS-vWF). Exposure of human umbilical
      vein EC (HUVEC) to tumor necrosis factor-alpha (TNF-alpha) or to TNF-alpha in
      combination with interferon-gamma (IFN-gamma), but not to interleukin-1beta (IL
      1), increased attachment to RADS-vWF by about twofold. The TNF-alpha-induced
      increase in EC attachment was accompanied by an increase in cell surface GP Ib
      alpha expression; GP Ib alpha surface expression was not increased by IL-1.
      Attachment of untreated HUVEC to WT-vWF could be inhibited 60% to 70% by a
      monoclonal antibody (MoAb) (LM609) to the VNR and 30% to 40% by the A1 fragment
      of vWF (containing the GP Ib alpha binding domain). The pattern of inhibition of
      attachment to WT-vWF was largely unchanged after TNF-alpha treatment of HUVEC. In
      contrast, the attachment to WT-vWF of HUVEC, treated with TNF-alpha +IFN-gamma
      was completely inhibited by vWF-A1 and inhibited only 35% by the anti-VNR
      antibody LM609. Two MoAbs to GP Ib alpha produced similar, but incomplete,
      inhibition. Pretreatment of HUVEC with the combination of TNF-alpha + IFN-gamma
      produced a dramatic decrease in VNR expression, confirming previous findings of
      Defilippi et al. These results suggest that in the presence of the inflammatory
      cytokines TNF-alpha + IFN-gamma, the endothelial GP Ib complex is a major
      determinant of HUVEC adhesion to surface-bound vWF.

PMID- 9166848
TI  - 7E3 F(ab')2, a monoclonal antibody to the platelet GPIIb/IIIa receptor, protects
      against microangiopathic hemolytic anemia and microvascular thrombotic renal
      failure in baboons treated with C4b binding protein and a sublethal infusion of
      Escherichia coli.
AB  - We have used our previously described baboon model of infusion of both a
      sublethal dose of Escherichia coli and C4b binding protein to assess the impact
      of inhibiting platelet function with the F(ab')2 fragment of the monoclonal
      antibody 7E3, directed against the platelet glycoprotein (GP)IIb/IIIa receptor,
      on the characteristic microvascular changes. At a dose of 0.25 to 0.35 mg/kg
      bolus plus an infusion of 0.25 to 0.35 mg/kg over 6 hours, c7E3 F(ab')2 had only
      a minimal impact on fibrinogen consumption and delayed but did not prevent, the
      development of thrombocytopenia. Treatment with 7E3 F(ab')2, however, produced
      significant protection from the development of microangiopathic hemolysis and
      renal insufficiency. Histologic examination supported these observations, with
      treated animals having fewer schistocytes on blood smear and less evidence of
      ischemic renal changes. Treated animals also had more rapid recovery of
      peripheral white blood counts, suggesting a possible protective effect of
      treatment on ischemic damage to the bone marrow. These data indicate that potent
      inhibition of platelet function via GPIIb/IIIa receptor blockade can decrease
      ischemic organ damage in this animal model that has features similar to those
      found in diffuse intravascular coagulation, hemolytic uremic syndrome, and
      thrombotic thrombocytopenic purpura.

PMID- 9166849
TI  - Mechanisms responsible for granzyme B-independent cytotoxicity.
AB  - Using granzyme B-deficient mice obtained by gene targeting, we previously
      demonstrated that granzyme B is required for the rapid induction of apoptotic
      target cell death by cytotoxic T lymphocytes (CTLs); however, CTLs are also
      equipped with additional effector mechanisms. In the present study, we examined
      the mechanisms responsible for granzyme B-independent cytotoxicity using in vitro
      lytic assays with CTLs derived from mice deficient for both granzyme B and Fas
      ligand (FasL) (granzyme B-/- x gld/gld) or for perforin and FasL (perforin x
      gld/gld). Our results show that primary mixed lymphocyte reaction (MLR)-derived
      CTLs from granzyme B-/- x gld/gld mice induce apoptosis of allogeneic targets
      with less efficiency and a longer delay than CTLs deficient for granzyme B alone.
      The residual cytotoxicity in granzyme B-/- x gld/gld CTLs is primarily accounted
      for by a perforin-dependent mechanism, since perforin-/- x gld/gld CTLs have
      virtually no residual cytotoxic activity in our assays. Granzyme B-independent
      cytotoxicity is therefore partially accounted for by the Fas pathway and
      partially by another perforin-dependent mechanism.

PMID- 9166850
TI  - Control of cell cycle progression in human natural killer cells through redox
      regulation of expression and phosphorylation of retinoblastoma gene product
      protein.
AB  - Using thiol deprivation, we have previously shown that the response of natural
      killer (NK) cells to interleukin-2 (IL-2) is subject to redox regulation
      downstream of IL-2 binding and internalization. We have now used the IL-2
      dependent cell line, NK3.3 to study redox regulation of NK cells further, and
      found that NK3.3 cells neither incorporated [3H]-thymidine nor completed the G1-S
      phase transition in medium lacking the thiol-related compounds, L-cystine, and
      glutathione, despite the presence of sufficient IL-2. Thiol deprivation did not
      alter the induction of DNA interferon-gamma activated sequence (GAS)-binding
      activity in response to IL-2. However, the retinoblastoma gene product (RB), a
      cyclin-dependent kinase (CDK) substrate, was phosphorylated within 24 hours after
      IL-2 stimulation in standard medium, but its expression and phosphorylation were
      reduced in thiol-depleted medium in both NK3.3 cells and freshly isolated NK
      cells. These reductions were not associated with an increased level of p27Kip1,
      an inhibitor of CDKs CDK6/2 in association with G1 cyclins. Reducing agents, N
      acetylcysteine, reduced glutathione or 2-ME restored both RB phosphorylation and
      DNA synthesis in thiol-deprived NK3.3 cells. The in vitro kinase activities of
      CDK6 and CDK2 were prematurely increased by thiol deprivation. This enhancement
      was associated with CDK hyperphosphorylation and prolonged phosphorylation, and
      could be observed before and beyond IL-2 stimulation. The data suggest the
      possibility that the premature and prolonged enhancement of CDK activity in thiol
      deprived NK cells is associated with, and therefore may contribute to, the
      reduced expression and phosphorylation of RB, and the associated cell cycle
      arrest.

PMID- 9166851
TI  - Cytokine production regulating Th1 and Th2 cytokines in hemophagocytic
      lymphohistiocytosis.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is caused by the hyperactivation of T
      cells and macrophages. The clinical characteristics associated with this disease
      result from overproduction of Th1 cytokines including interferon-gamma (IFN
      gamma), interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNF-alpha). In
      this study, we analyzed the production of IL-12 and IL-4, which determine Th1 and
      Th2 response, respectively, and IL-10, which antagonizes Th1 cytokines, in 11
      patients with HLH. IL-12 was detected in plasma in all patients (mean peak value,
      30.0 +/- 5.0 pg/mL), while IFN-gamma was massively produced in nine patients
      (mean peak value, 79.2 +/- 112.0 U/mL). IL-4 was not detected in any of the
      patients. Plasma IL-10 levels were elevated in all patients (mean peak value,
      2,698.0 +/- 3,535.0 pg/mL). There was a positive correlation between the levels
      of IFN-gamma and IL-10 (P < .01). The plasma concentrations of these cytokines
      were initially high, before decreasing after the acute phase. However, the
      decrease in IL-10 levels was slower than that of IFN-gamma. Although the
      concentration of IL-12 was high at the acute phase, in some patients, a peak in
      the level was delayed until the chronic phase. Thus, in HLH, production of
      cytokines that promote development of Th1 cells appears to be predominant over
      that for Th2 cell development. Overproduction of IL-10 was also observed
      indicating that a mechanism suppressing hyperactivation of Th1 cells and
      monocytes/macrophages functions in patients with this disease.

PMID- 9166852
TI  - Molecular mechanisms of monocyte adhesion to interleukin-1beta-stimulated
      endothelial cells under physiologic flow conditions.
AB  - This study identifies multiple pathways used by monocytes to adhere to 4-hour
      interleukin-1beta stimulated human umbilical vein endothelial cells under flow
      conditions. Physiologic shear stresses were simulated in a flow chamber with
      parallel plate geometry; quantitation of primary adhesion, secondary adhesion,
      and transmigration was performed using phase contrast videomicroscopy.
      Neuraminidase treatment of monocytes reduced primary interaction by 50%, whereas
      blocking L-selectin or very late antigen-4 showed significant but smaller effects
      (approximately 30% inhibition). However, a combined treatment against all three
      pathways was able to reduce interaction by 80%. Blocking beta2 and alpha4
      integrin pathways together inhibited secondary/firm adhesion by 75%. Only 40% of
      firmly adherent monocytes transmigrated across the endothelial monolayer with
      significantly increased transmigration times when both beta2 and alpha4 integrins
      were blocked. These results demonstrate that monocytes can use multiple receptors
      to interact with endothelial cells at both primary and secondary adhesion stages,
      and that these pathways have to be blocked simultaneously for maximum inhibition.

PMID- 9166853
TI  - Regulation of interleukin-10 gene expression: possible mechanisms accounting for
      its upregulation and for maturational differences in its expression by blood
      mononuclear cells.
AB  - Interleukin-10 (IL-10) downmodulates phagocytic immune responses and accentuates
      humoral responses. Human neonates exhibit broad immune deficits that parallel
      actions of IL-10. We postulated that IL-10 production would be diminished in
      neonatal blood cells. We found that IL-10 production by lipopolysaccharide
      stimulated peripheral blood mononuclear cells (PBMNCs) in vitro was greater by
      adult cells than by term cells and preterm cells. Additional studies were
      undertaken to identify mechanisms responsible for the developmental differences
      in IL-10 gene expression. IL-10 transcription was present in freshly isolated
      adult and neonatal cells in the absence of detectable levels of transcript.
      Transcription rates were not different between adult and neonatal cells. IL-10
      transcripts were approximately 40% more abundant in adult cells than in term
      cells and were consistent with differences in secreted protein; however, no
      differences were noted in mRNA stability. IL-10 half-life was 60 minutes for both
      adult and term PBMNCs. We conclude that up-regulation of IL-10 gene expression in
      PBMNCs is modulated at the post-transcriptional level, that IL-10 protein
      production and mRNA content are greater in activated cells from adults compared
      with those from neonates, and that maturational differences in IL-10 expression
      are not due to differences in transcription rate or mRNA stability. Maturational
      differences in IL-10 expression might be due to differences in subpopulations of
      cytokine-producing cells or differences in nucleo-cytoplasmic transport.

PMID- 9166854
TI  - Impact of Rantes and MCP-1 chemokines on in vivo basophilic cell recruitment in
      rat skin injection model and their role in modifying the protein and mRNA levels
      for histidine decarboxylase.
AB  - RANTES and related molecules, constitute the C-C class of chemokine supergene
      family and a group of cytokines produced by hematopoietic cells constitute the
      MCP-1 or C-X-C class. The roles of most of these chemokines are not well known,
      although members of the C-X-C family are inflammatory agents. Here, we report
      that intradermal injection of RANTES 10 ng/50 microL subcutaneously in the
      abdominal skin produced a strong inflammatory reaction, as evidenced by Evans
      blue dye, greater than FMLP (10(-6) mol/L) (approximately 57%); while MCP-1, 10
      ng/50 microL was less effective than FMLP (10(-6) mol/L) (approximately 54%).
      Moreover, the histologic analysis of the cells stained with Toluidine blue (0.1%)
      were analyzed at a magnification of x40). RANTES 10 ng/50 microL and LPS produced
      higher numbers (142 +/- 11 and 193 +/- 21 of cells/200 mm2, respectively) of
      basophilic cell accumulation in the skin injection sites compared with FMLP (10(
      6) mol/L) (127 +/- 14/200 mm2), while MCP-1 10 ng/50 microL was less effective
      (88 +/- 10/200 mm2). Electron microscopy (x13,800) studies of skin injection
      sites revealed that RANTES was chemoattractant for mast cells. In a Northern blot
      analysis from homogeneous tissue biopsy from the intradermal injection sites,
      RANTES was more potent than MCP-1 in increasing histidine decarboxylase (HDC)
      mRNA, the sole enzyme responsible for the production of histamine from histidine.
      Since PGD2 is formed by mast cells on cell activation, we also studied the effect
      of RANTES and MCP-1 on PGD2 production in inflamed tissue in vivo. RANTES (20,
      10, and 5 ng) and MCP-1 (20, 10, and 5 ng) strongly stimulated PGD2, in a dose
      dependent manner, with a potency rank order of RANTES (10 ng/mL) approximately
      two times greater than MCP-1 (10 ng/mL).

PMID- 9166855
TI  - Activation of human T cells by major histocompatability complex class II
      expressing neutrophils: proliferation in the presence of superantigen, but not
      tetanus toxoid.
AB  - The primary function of polymorphonuclear neutrophils (PMN) in the immune
      response appears to be acute phagocytic clearance of foreign pathogens and
      release of inflammatory mediators. Consistent with their assumed lack of major
      histocompatibility complex (MHC) class II expression, PMN have not been
      considered to play a role in antigen presentation and T-cell activation. However,
      recent reports have shown that human PMN can express MHC class II molecules both
      in vitro and in vivo after stimulation with either granulocyte-macrophage colony
      stimulating factor (GM-CSF) or interferon-gamma (IFN-gamma). Thus, under
      appropriate conditions, PMN could play a significant role in immune regulation,
      including T-cell activation. In this report, we demonstrate that human class II
      expressing PMN can serve as accessory cells in superantigen (SAg)-mediated T-cell
      activation. This accessory activity for SAg presentation was present only after
      induction of MHC class II expression, and was especially pronounced following
      culture of PMN with GM-CSF plus IFN-gamma, which acted synergistically to induce
      MHC class II molecules on PMN. Moreover, the level of MHC class II expression and
      the magnitude of SAg-induced T-cell responses were found to be highly correlated
      and distinctly donor dependent, with PMN from some donors repeatedly showing
      fivefold higher responses than PMN from other donors. On the other hand, culture
      of PMN with GM-CSF plus IFN-gamma under conditions that resulted in optimal MHC
      class II expression did not enable them to function as antigen-presenting cells
      for either intact tetanus toxoid (TT) or for a TT peptide. These results
      delineate a new pathway for T-cell activation by SAg that may play an important
      role in the severity of SAg-induced inflammatory responses. They also identify a
      donor-specific polymorphism for induction of PMN MHC class II expression which
      may be of significance for therapies involving GM-CSF and IFN-gamma.

PMID- 9166856
TI  - The type 2 CD10/neutral endopeptidase 24.11 promoter: functional characterization
      and tissue-specific regulation by CBF/NF-Y isoforms.
AB  - The cell surface zinc metalloproteinase CD10/neutral endopeptidase 24.11 ([NEP]
      neprilysin) functions as part of a regulatory loop to control local
      concentrations of peptide substrates and associated peptide-mediated signal
      transduction. The physiologic role of the enzyme depends on available substrates
      in specific organs and cell types. Although CD10/NEP is expressed on a restricted
      subset of normal and malignant lymphoid progenitors, the enzyme is also expressed
      by a variety of epithelial cells. To explore the mechanism of tissue-specific
      expression of this regulatory enzyme, we characterized the major (type 2)
      CD10/NEP promoter and identified three functionally active transcription factor
      binding sites (regions I to III). CBF/NF-Y binds to the inverted CCAAT box in
      region I, whereas a second positive and a third negative factor bind to regions
      II and III, respectively. Although region I is required for maximal CD10/NEP
      driven luciferase activity in the examined epithelial cell lines, this region is
      not required for maximal activity in the evaluated lymphoid cell lines. The
      apparent tissue-specific differences in requirements for region I (and CBF/NF-Y)
      are of particular interest because lymphoid and epithelial cells express
      alternatively spliced versions of CBF/NF-Y that differ in biologic activity.

PMID- 9166858
TI  - Differential rates of somatic hypermutation in V(H) genes among subsets of
      chronic lymphocytic leukemia defined by chromosomal abnormalities.
AB  - Chronic lymphocytic leukemia (CLL) is a B-cell tumor involving small lymphocytes
      that generally express the CD5 antigen and low levels of surface Ig. Within this
      definition, there is heterogeneity among cases in cell morphology, karyotypic
      abnormalities, and clinical course. Trisomy 12, the most frequent karyotypic
      abnormality, is commonly found in a subset of CLL with atypical morphology. It
      has also been associated with advanced disease, and possibly with a less
      favorable prognosis. A further subset of cases with abnormalities involving
      chromosome 13q14 have typical lymphocyte morphology. Occasionally, the two
      abnormalities are found together. To assess the clonal history of the cell of
      origin in disease subsets defined by these two chromosomal abnormalities, we
      investigated the usage of V(H) genes and the pattern of somatic mutation in 10
      cases of trisomy 12 with atypical morphology and eight cases of 13q14 abnormality
      with typical morphology. In addition, four cases with both chromosomal
      abnormalities were analyzed. Results confirm a common usage of the V(H)1 family
      in all subsets. However, the patterns of somatic mutation were distinct, with
      cases of trisomy 12 showing a minimal level of mutation (mean +/- SD, 0.34% +/-
      0.86%) and cases of 13q14 abnormality showing significant levels (6.5% +/-
      1.67%). The four cases with both abnormalities showed a mixed pattern. All
      mutated cases had intraclonal homogeneity, and three of 10 had a pattern
      indicative of antigen selection. These results suggest that the clonal history of
      the two subsets of CLL may differ.

PMID- 9166857
TI  - Characterization of interleukin-10 receptor expression on B-cell chronic
      lymphocytic leukemia cells.
AB  - B-cell chronic lymphocytic leukemia (B-CLL) cells accumulate in vivo in the G0/G1
      phase of the cell cycle, suggesting that their malignant expansion is due, at
      least in part, to a delay in cell death. However, the cellular or molecular
      factors responsible for a delay in B-CLL cell death are unknown. B-CLL cells do
      express receptors for interferon-alpha (IFN-alpha) and IFN-gamma, and activation
      of both has been shown to promote B-CLL survival in vitro by preventing
      apoptosis. The interleukin-10 (IL-10) receptor is another member of the IFN
      receptor family, but its ligand, IL-10, has been reported to induce apoptosis in
      B-CLL cells. In the current study, we undertook a biochemical analysis of IL-10
      receptor expression on freshly isolated B-CLL cells and characterized the
      functional responsiveness of IL-10 binding to its constitutively expressed
      receptor. We show that B-CLL cells bind IL-10 with significant specificity and
      express between 47 and 127 IL-10 receptor sites per cell, with a dissociation
      constant in the range of 168 to 426 x 10(-12) mol/L. Ligand binding and
      activation of the IL-10 receptor expressed on B-CLL cells results in the
      phosphorylation of signal transducer and activator of transcription 1 (STAT1) and
      STAT3 proteins. This pattern of STAT protein phosphorylation is identical to IL
      10 receptor activation on normal cells and similar to IFN-alpha (STAT1 and STAT3)
      and IFN-gamma (STAT1) receptor activation in CLL. Further, in consecutive samples
      of fresh blood obtained from patients with B-CLL cells, the addition of IL-10
      inhibited B-CLL proliferation, enhanced B-CLL differentiation, but did not induce
      apoptosis. Indeed, IL-10, like IFN-gamma, was able to significantly reduce the
      amount of B-CLL cell death caused by hydrocortisone-induced apoptosis. We
      conclude that cytokines, which signal through the interferon family of receptors,
      have comparable functional effects on B-CLL cells.

PMID- 9166859
TI  - Homozygous deletion of the p16/MTS1 gene in pediatric acute lymphoblastic
      leukemia is associated with unfavorable clinical outcome.
AB  - The p16 gene (MTS1, CDKN2, p16INK4A, CDKI) encoding an inhibitor of cyclin
      dependent kinase 4 (cdk4) has been found to be deleted in various types of
      tumors, including leukemia, and is thought to code for a tumor suppressor gene.
      Our preliminary findings on eight pediatric patients with acute lymphoblastic
      leukemia (ALL) suggested that the survival of patients carrying a homozygous p16
      gene deletion was significantly inferior to that of those without a deletion. The
      present study on 48 patients tested the hypothesis that the clinical outcome for
      pediatric ALL patients is correlated with the presence or absence of the p16
      gene. Overall, nine of 48 children (18.3%) carried a homozygous p16 deletion.
      Such deletions were significantly more common (P = .003) among T-ALL patients
      (five of eight, 62.5%) than among precursor-B-ALL patients (four of 40, 10.0%).
      Of nine patients exhibiting p16 deletions, eight (88.9%) were classified as high
      risk patients by the recognized prognostic factors of age, white blood cell
      count, and T-cell phenotype. The 4-year event-free survival in the study
      population as a whole was 72.7%. Without adjustment for other risk factors
      (univariate model), the presence of a homozygous p16 deletion was associated with
      a markedly increased probability of both relapse (P = .0003) and death (P =
      .002). These findings raise the question of whether the p16 deletion itself
      confers an increased risk of relapse after adjusting for the known risk factors.
      In this analysis, the estimated risk multiplier factor for relapse in patients
      carrying the p16 deletion was 14.0 (P = .0004) and for the risk of death 15.6 (P
      = .0008). We therefore conclude that the presence of a homozygous p16 deletion
      may well be an important risk factor for both relapse and death in childhood ALL,
      and that its prognostic effect is not a consequence of confounding by other
      factors already known to influence outcome in this disease.

PMID- 9166860
TI  - Tumor necrosis factor constellation polymorphism and clozapine-induced
      agranulocytosis in two different ethnic groups.
AB  - Genes of the major histocompatibility complex (MHC) are associated with
      susceptibility to different immune and nonimmune mediated diseases. We had
      reported that the drug adverse reaction, clozapine-induced agranulocytosis (CA),
      is associated with different HLA types and HSP70 variants in Ashkenazi Jewish and
      non-Jewish patients, suggesting that a gene within the MHC region is associated
      with CA. This study was designed to find common genetic markers for this disorder
      in both ethnic groups. The tumor necrosis factor (TNF) microsatellites d3 and b4
      were found in higher frequencies in both Jewish and non-Jewish patients: 51 of 66
      (77%) and 48 of 66 (57%), respectively. Comparisons of these frequencies with
      those of controls, 28 of 66 (42%) and 18 of 66 (27%), were statistically
      significant (corrected P value = .001 for the d3 allele and .0005 for the b4
      allele). On the other hand, the TNF microsatellite b5 was underrepresented in the
      group of patients, 9 of 66 (14%), when compared with the control subjects, 43 of
      66 (65%) (corrected P value = .0005), probably related to protection from CA. Our
      results show a strong association of some genetic variants of the TNF loci with
      susceptibility to CA in two different ethnic groups suggesting involvement of TNF
      and/or associated gene(s) products in the pathogenesis of this hematologic-drug
      adverse reaction.

PMID- 9166861
TI  - Augmented intracellular glutathione inhibits Fas-triggered apoptosis of activated
      human neutrophils.
AB  - Agonist signals delivered through cell surface Fas induce apoptosis. However, the
      apoptotic program can be modulated by signals from the environment, and in
      particular, by signals delivered through adhesion molecules. Because neutrophil
      functional activity in inflammation is contingent on cell survival, and because
      circulating neutrophils normally die rapidly through a constitutively expressed
      apoptotic program, we evaluated Fas-mediated apoptosis in resting and
      inflammatory human neutrophils. We show that normal neutrophils respond to Fas
      engagement with accelerated rates of apoptosis, but cross-linking of beta2
      integrins or priming with bacterial lipopolysaccharide (LPS) prevents this
      increase. Adhesion molecule cross-linking results in increased intracellular
      glutathione (GSH). Augmentation of intracellular GSH with exogenous GSH or N
      acetylcysteine is sufficient to reduce the Fas-triggered increase in apoptotic
      rates. Prevention of the activation induced GSH increase by buthionine
      sulfoximine, a cell permeable inhibitor of GSH biosynthesis, restored Fas
      responsiveness in activated neutrophils, an effect that could be blocked with
      exogenous GSH. Taken together, these data show that Fas-induced signaling for
      neutrophil apoptosis is blocked in a redox sensitive manner by costimulatory
      signals delivered through beta2 integrins or activation by LPS, and provide a
      biologic explanation for sustained neutrophil survival in the inflammatory
      environment.

PMID- 9166862
TI  - Fibronectin enhances in vitro lipopolysaccharide priming of polymorphonuclear
      leukocytes.
AB  - We investigated the role of humoral factors in lipopolysaccharide (LPS) priming
      of polymorphonuclear leukocytes (PMN) using cells isolated from adults and from
      neonates. Plasma from newborn infants had decreased priming activity of adult
      plasma when mixed with LPS in studies measuring oxidative radical production of
      PMN after stimulation with a formyl bacterial oligopeptide (fMLP). This marked
      difference was not caused by LPS binding protein (LBP) because the LBP
      concentration in newborn and adult plasma were similar (138.4 +/- 12.9 U for
      adults, and 126.9 +/- 12.1 U for neonates, P = .53). Therefore, we attempted to
      identify other plasma factors that may contribute to LPS priming of PMN. We
      identified an LPS priming factor for PMN that is present in plasma, heat stable
      (56 degrees C for 30 minutes), enhanced by heparin, and concentrated in cold
      precipitates of plasma. Because these properties resemble those of plasma
      fibronectin, we assessed the role of fibronectin in LPS priming of PMN. Although
      fibronectin in phosphate-buffered saline (PBS) had little effect on LPS priming
      of PMN, fibronectin in combination with other plasma factors appeared to play a
      role in LPS priming of PMN because (1) removing fibronectin from adult plasma
      dramatically decreased LPS priming activity from plasma (P < .005), (2) addition
      of fibronectin to fibronectin-depleted plasma restored its LPS plasma priming
      activity (P < .05), and (3) neutralizing fibronectin with antibody decreased the
      LPS priming activity of plasma (60.3 +/- 1.3 v 30.2 +/- 2.2, P < .01). Thus,
      plasma fibronectin plays a role in LPS priming of PMN in the presence of other
      factors in plasma.

PMID- 9166864
TI  - Recombinant sickle hemoglobin containing a lysine substitution at Asp-85(alpha):
      expression in yeast, functional properties, and participation in gel formation.
AB  - Clinical modalities based on inhibition of gelation of HbS are hindered by the
      lack of quantitative information on the extent of participation of different
      amino acid residues in the aggregation process. One such site is Asp-85(alpha),
      which is involved in a parallel interdouble strand ionic interaction with Lys
      144(beta) according to the crystal structure of HbS, but electron microscopy does
      not specifically show Asp-85(alpha) as a contact site for fiber formation. Using
      a yeast recombinant system, we have substituted this site by Lys to abolish ion
      pairing and to make a quantitative determination of its participation in
      aggregation. The purified double mutant was shown to have the expected pI, the
      calculated molecular weight, correct amino acid composition, and peptide map. The
      recombinant double mutant has an oxygen affinity of 10 mm Hg, which is identical
      to that for HbA and HbS under the same conditions; it also has high cooperativity
      with an average n value of 2.7. The change in P50 in response to chloride ions
      was about 25% less than that for HbA or HbS and is ascribed to the introduction
      of a new positive charge near one of the major oxygen-linked chloride binding
      sites of hemoglobin. The gelation concentration of the double mutant was measured
      by a new procedure (Bookchin et al, 1994); the maximal amount of soluble
      hemoglobin (Csat) in the presence of dextran indicated a decreased tendency for
      gelation with a Csat of 53 mg/mL compared with 34 mg/mL for HbS. This inhibitory
      effect is smaller than that of the E6V(beta)/L88A(beta) (Csat, 67 mg/mL) and the
      E6V(beta)/K95I(beta) (Csat, 90 mg/mL) recombinant hemoglobins. Thus, we would
      classify Asp-85(alpha) as a moderate contributor to the strength of the HbS
      aggregate. This wide range of gelation values demonstrates that some sites are
      more important than others in promoting HbS aggregation.

PMID- 9166863
TI  - Human erythrocytes express GLUT5 and transport fructose.
AB  - Although erythrocytes readily metabolize fructose, it has not been known how this
      sugar gains entry to the red blood cell. We present evidence indicating that
      human erythrocytes express the fructose transporter GLUT5, which is the major
      means for transporting fructose into the cell. Immunoblotting and
      immunolocalization experiments identified the presence of GLUT1 and GLUT5 as the
      main facilitative hexose transporters expressed in human erythrocytes, with GLUT2
      present in lower amounts. Functional studies allowed the identification of two
      transporters with different kinetic properties involved in the transport of
      fructose in human erythrocytes. The predominant transporter (GLUT5) showed an
      apparent Km for fructose of approximately 10 mmol/L. Transport of low
      concentrations of fructose was not affected by 2-deoxy-D-glucose, a glucose
      analog that is transported by GLUT1 and GLUT2. Similarly, cytochalasin B, a
      potent inhibitor of the functional activity of GLUT1 and GLUT2, did not affect
      the transport of fructose in human erythrocytes. The functional properties of the
      fructose transporter present in human erythrocytes are consistent with a central
      role for GLUT5 as the physiological transporter of fructose in these cells.

PMID- 9166865
TI  - A transgenic mouse model of hemoglobin S Antilles disease.
AB  - Hemoglobin (Hb) S Antilles is a naturally occurring form of sickling human Hb but
      causes a more severe phenotype than Hb S. Two homozygous viable Hb S Antilles
      transgene insertions from Tg58Ru and Tg98Ru mice were bred into MHOAH mice that
      express high oxygen affinity (P50 approximately 24.5 mm Hg) rather than normal
      (P50 approximately 40 mm Hg) mouse Hbs. The rationale was that the high oxygen
      affinity MHOAH Hb, the lower oxygen affinity of Hb S Antilles than Hb S (P50
      approximately 40 v 26.5 mm Hg), and the lower solubility of deoxygenated Hb S
      Antilles than Hb S (approximately 11 v 18 g/dL) would favor deoxygenation and
      polymerization of human Hb S Antilles in MHOAH mouse red blood cells (RBCs). The
      Tg58 x Tg98 mice produced have a high and balanced expression (approximately 50%
      each) of h alpha and h beta(S Antilles) globins, 25% to 35% of their RBCs are
      misshapen in vivo, and in vitro deoxygenation of their blood induces 30% to 50%
      of the RBCs to form classical looking, elongated sickle cells with pointed ends.
      Tg58 x Tg98 mice exhibit reticulocytosis, an elevated white blood cell count and
      lung and kidney pathology commonly found in sickle cell patients, which should
      make these mice useful for experimental studies on possible therapeutic
      intervention of sickle cell disease.

PMID- 9166866
TI  - Frame shift mutation, exon skipping, and a two-codon deletion caused by splice
      site mutations account for pyruvate kinase deficiency.
AB  - Three novel splice site mutations and two novel missense mutations were
      identified by molecular analysis of pyruvate kinase (PK) deficiency associated
      with hereditary nonspherocytic hemolytic anemia. A Nepalese PK variant, PK
      Kowloon, was found to have a homozygous transversion at the 5'-splice site of the
      seventh intervening sequence (IVS) of the L-type PK gene (Ivs7[+1]gt --> tt).
      Using a reverse transcription polymerase chain reaction (RT-PCR) assay, we showed
      that the R-type PK mRNA in the proband's reticulocytes included the seventh IVS
      between the seventh and eighth exon, introducing a stop codon 3 nucleotides
      downstream of the mutated site. Consequently, the translational product may lack
      44% of the R-PK polypeptide. A transition at the last nucleotide of exon 9
      (1269GCG --> GCA) was found in a Japanese PK variant, PK 'Kamata.' The mutation
      did not alter the amino acid sequence, but caused skipping of the ninth exonic
      sequence in the R-PK transcripts. As a result, the affected R-type PK lost 51
      amino acid residues (373Met-423Ala del). A transversion at the splice acceptor
      site of the third IVS (Ivs 3[-2]ag --> tg) was identified in PK 'Aomori.' The
      mutation resulted in aberrant splicing at a cryptic splice site within exon 4,
      causing deletion of two codons in the aberrant R-PK transcript (95 Gly-96 Pro -->
      del). Both PK 'Kamata' and PK 'Aomori' had a missense mutation on the other
      allele, 1044AAG --> AAT (348Lys --> Asn) and 1075CGC --> TGC (359Arg --> Cys),
      respectively. Although both 348Lys and 359Arg were located in the sixth loop of A
      domain (beta/alpha)8 barrel, which has been shown to contain the substrate and
      cation binding sites, the degree of anemia was much more severe in PK 'Kamata'
      than PK 'Aomori,' possibly because the 51 amino acid deletion of PK 'Kamata' but
      the 2 amino-acid deletion of PK 'Aomori' may abolish PK catalytic activity.

PMID- 9166867
TI  - Use of domain-deletion mutants to locate Lutheran blood group antigens to each of
      the five immunoglobulin superfamily domains of the Lutheran glycoprotein:
      elucidation of the molecular basis of the Lu(a)/Lu(b) and the Au(a)/Au(b)
      polymorphisms.
AB  - Lutheran glycoprotein (Lu gp) has five predicted immunoglobulin superfamily
      (IgSF) domains. K562 cells were transfected with Lu cDNA and tested by flow
      cytometry with monoclonal antibodies and Lu blood group antisera. The results
      confirmed the identity of Lu cDNA. Deletion mutants lacking the regions encoding
      one or more IgSF domains were made by inverse polymerase chain reaction (PCR),
      expressed in K562 cells, and tested with the same antibodies. The Lu(b) and Lu5
      antigens and the epitope recognized by monoclonal antibody BRIC 224 were mapped
      to the first, N-terminal, IgSF domain. Lu4 and Lu8 were mapped to domain 2; Lu20
      to domain 3; Lu7 and BRIC 221 epitope to domain 4, and Lu13 and Au(b) to domain
      5. The organization of the LU gene was determined. The region encoding the open
      reading frame is arranged in 15 exons extending over approximately 11 kb on
      chromosome 19q13.2. The Lu(a)/Lu(b) and Au(a)/Au(b) blood group polymorphisms
      were studied using genomic DNA from typed blood donors. The Lu(a) mutation is a
      base change in exon 3 (G252 to A) encoding an Arg77 (Lu(b)) to His (Lu(a)) change
      on the CFG face of domain 1. The Au(a)/Au(b) polymorphism is an A1637 to G
      substitution in exon 12 encoding a Thr539 (Au(a)) to Ala (Au(b)) change on the G
      strand of domain 5.

PMID- 9166869
TI  - The importance of erythrocyte aggregation in blood rheology: considerations on
      the pathophysiology of thrombotic disorders.

PMID- 9166868
TI  - Transplantation of marrow cells from unrelated donors for treatment of high-risk
      acute leukemia: the effect of leukemic burden, donor HLA-matching, and marrow
      cell dose.
AB  - Transplantation of hematopoietic stem cells from an HLA-compatible unrelated
      volunteer is an option for patients with acute leukemia lacking a family match.
      However, criteria for patient and donor selection and the most effective
      transplant procedures, including the number of hematopoietic cells, remain to be
      defined. We tested factors influencing outcome of 174 patients with primary acute
      leukemia receiving non-T-cell depleted marrow from unrelated donors. Median
      patient age was 20 years (range, 0.5 to 54 years). A multivariable analysis found
      that leukemia in remission at the time of transplantation was associated with
      improved leukemia-free survival (relative risk [RR] of treatment failure: 0.5,
      confidence interval [CI]: 0.3 to 0.7), and presence of blasts in the peripheral
      blood, as opposed to marrow involvement only or isolated extramedullary relapse,
      was associated with impaired outcome (RR of treatment failure: 2.5, CI: 1.7 to
      5.0). The use of donors with a limited HLA-mismatch was associated with decreased
      leukemic relapse (RR: 0.5, CI: 0.3 to 0.9) but no improvement in leukemia-free
      survival compared with HLA-matched unrelated donors. Transplantation of a marrow
      cell dose above the median value of 3.65 x 10(8)/kg was associated with faster
      neutrophil (RR: 1.5, CI: 1.1 to 2.0) and platelet (RR: 4.5, CI: 2.7 to 7.5)
      engraftment, and decreased incidence of severe acute graft-versus-host disease
      (RR: 0.6, CI: 0.4 to 0.9). In patients transplanted in remission, the use of a
      marrow cell dose above the median translated into less nonleukemic death (RR:
      0.2, CI: 0.1 to 0.4) and better leukemia-free survival (RR of treatment failure:
      0.3, CI: 0.2 to 0.6). Transplant in remission with a high dose of marrow cells
      was associated with the best outcome in both children and adults.

PMID- 9166870
TI  - Leukocyte recovery and early treatment-related mortality after bone marrow
      transplantation.

PMID- 9166871
TI  - DAMI cell line.

PMID- 9166872
TI  - A new case of chronic myeloid leukemia with c3/a2 BCR/ABL junction. Is it really
      a distinct disease?

PMID- 9166873
TI  - Prognostic impact of the serum levels of soluble CD23 in B-cell chronic
      lymphocytic leukemia.

PMID- 9166874
TI  - Electrically evoked auditory brainstem response by direct electrical stimulation
      to the cochlear nerve in acoustic neuroma patients.
AB  - The electrically evoked auditory brainstem response (EABR) was recorded by direct
      electrical stimulation of the cochlear nerve in 8 acoustic neuroma patients. The
      EABR by electrical stimulation of the cochlear nerve at the fundus of the
      internal auditory canal was almost similar to those previously reported from
      cochlear implant patients in waveform morphology and wave latencies. However, the
      wave corresponding to wave II in human auditory ABR was not recorded in the EABRs
      by stimulation of the distal part of the intracranial cochlear nerve. These
      results suggest that the cochlear nucleus does not contribute to the generation
      of wave II in ABR.

PMID- 9166875
TI  - Iron deficiency anemia and hearing.
AB  - Iron deficiency anemia is a frequently occurring clinical disorder. Despite the
      suggested association with hearing loss in the literature, cochlear sequelae of
      iron deficiency have yielded conflicting results in experimental studies.
      Auditory function was tested in iron-deficient and normal male Wistar albino rats
      using distortion product otoacoustic emissions and auditory brainstem response
      audiometry for the clarification of the opposing results in the literature.
      Hemoglobin, hematocrit, serum iron and albumin levels were monitored to verify
      iron deficiency. Although dramatic differences in weight gain and blood test
      parameters were noted, no significant change in auditory function due to iron
      deficiency was detected.

PMID- 9166876
TI  - Effectiveness of hyperbaric oxygen therapy in patients with acute and chronic
      cochlear disorders.
AB  - Over the course of 18 months 359 patients with defined acute and chronic inner
      ear disorders who had not responded to treatment with medication were given
      hyperbaric oxygen (HBO) therapy. The inner ear diseases of the patients were
      divided, based on the duration of their conditions, into four symptomatic groups.
      Of the patients who had had hearing loss for less than 3 months, noticeable
      improvement or complete recovery was seen in 13% (20 dB in at least three test
      frequencies); 25.2% showed an improvement between 10 and 20 dB. Changes up to 10
      dB or less were not considered to be positive. Patients with a pretreated hearing
      loss for more than 3 months had markedly less benefit from HBO therapy. Two
      percent regained normal hearing function. In 30% an improvement of more than 10
      dB was achieved. For patients who had suffered from tinnitus for less than 3
      months excellent improvement was seen in 6.7% and noticeable improvement in 44.3%
      expressed by means of a visual analog scale. In 44.3% the tinnitus was described
      as unchanged. Patients who had had tinnitus for more than 3 months before HBO
      therapy showed a less favorable response to HBO. In none of the patients did the
      tinnitus disappear; 34.4% of the patients described a noticeable improvement in
      their complaints.

PMID- 9166877
TI  - Middle ear overpressure treatment of endolymphatic hydrops in guinea pigs.
AB  - Guinea pigs placed outside or inside a pressure chamber and exposed to 49.2 cm
      H2O overpressure continuously for 24 h immediately after blockage of the
      endolymphatic duct showed no significant difference in the magnitude of
      endolymphatic hydrops when compared to controls, although there was a slight
      indication of a volume decrease in the outside-treatment group and an increase in
      the inside-treatment group. A pressure increase of 49.2 cm H2O in the external
      auditory canal for 1 h twice a day for 2 weeks outside the chamber significantly
      inhibited the development of hydrops. The latter result supports the merit of
      pressure application through the external auditory canal as a treatment for
      Meniere's disease.

PMID- 9166878
TI  - Regeneration of olfactory mucosa in mice after inhalation exposure to
      perchloroethylene.
AB  - An experimental group of 20 male pure-bred mice was exposed to perchloroethylene
      gas at 300 ppm for 6 h daily for 5 days. Histopathological study of the nasal
      mucosa, particularly the olfactory mucosa, was performed sequentially 2 weeks to
      3 months after exposure, to clarify the process of regeneration. The tissue
      damage due to perchloroethylene gas was more persistent in the nasal mucosa of
      the olfactory region than in the respiratory region. Two weeks after exposure,
      ciliated epithelial cells, as well as normal pseudostratified nonciliated
      columnar epithelium, began to appear in the area previously covered by olfactory
      epithelium and remained for up to 3 months after exposure. A basement membrane
      was present under the ciliated epithelium, suggesting a possible persistence of
      basal cells. The olfactory epithelium may thus be replaced by ciliated
      epithelium. The lamina propria of the olfactory mucosa, however, lost its normal
      structure with atrophy of the olfactory nerves and Bowman's glands.

PMID- 9166879
TI  - No Epstein Barr and cytomegalovirus DNA found in salivary gland tumours.
AB  - A series of 219 (106 malignant and 113 benign) salivary gland tumours was
      investigated by in situ hybridisation (ISH) to detect Epstein-Barr-virus (EBV)
      and cytomegalovirus (CMV) DNA. Normal salivary gland did not show hybridisation
      signals for these viruses. Tumours presenting hybridisation signals in ductal and
      myoepithelial cells and 17 Warthin's tumours were further studied by PCR, but
      none of these tumours contained EBV or CMV DNA. Our series did not contain
      lymphoepithelial carcinomas, which are EBV-associated tumours. The results
      suggest that factors other than EBV or CMV are involved in carcinogenesis of
      primary salivary gland tumours.

PMID- 9166880
TI  - Videoendoscopic biofeedback: a simple method to improve the efficacy of
      swallowing rehabilitation of patients after head and neck surgery.
AB  - The value of flexible videoendoscopy as a biofeedback tool in conservative
      swallowing rehabilitation of patients suffering from aspiration after head and
      neck surgery was examined. For this purpose, the outcomes of conventional
      swallowing therapy and of swallowing therapy with support of videoendoscopic
      biofeedback were compared. In the first 40 days of swallowing therapy,
      videoendoscopic biofeedback significantly increased the chance of therapeutic
      success, shortening the period of functional rehabilitation in comparison to
      conventional swallowing therapy. Limitations of this visual biofeedback procedure
      are poor cognitive skills of the patient, rejection of the procedure by the
      patient and local factors that make the positioning of the endoscope difficult.

PMID- 9166881
TI  - Evaluation of TATI and CYFRA 21-1 in patients with head and neck squamous cell
      carcinoma.
AB  - This preliminary nonrandomized study was conducted to evaluate the clinical
      usefulness of TATI and CYFRA 21-1 as tumor markers in head and neck squamous cell
      carcinoma. Serum levels of these markers were measured from 122 subjects of a
      tertiary-care university hospital, divided into four groups: (1) normal
      individuals and patients with (2) inflammatory pathology, (3) benign tumors and
      (4) squamous cell carcinoma of the head and neck. Serum samples were collected
      before and after treatment, with a mean follow-up period of 12 months. The cutoff
      level, sensitivity, specificity and likelihood ratio of a positive and negative
      test were: 21 microg/l, 66.6%, 93.75%, 10.6 and 0.35 for TATI; 3.3 microg/l,
      28.5%, 95%, 5.7 and 0.75 for CYFRA 21-1, respectively. Both markers presented
      elevated mean values and statistically significant differences in the cancer
      patient group compared with the other groups. Significant differences were also
      observed between the stage of disease and tumor differentiation. TATI levels seem
      to relate positively to the course of disease during the follow-up period.
      Although CYFRA 21-1 values presented significant differences, the majority of
      them were under the cutoff level. We conclude that TATI seems to play a role in
      the clinical evaluation of head and neck squamous cell carcinoma, while the
      usefulness of CYFRA 21-1 is limited.

PMID- 9166882
TI  - Fistula of stapes footplate caused by pulsatile cerebrospinal fluid in inner ear
      malformation.
AB  - Congenital malformations of the inner ear are well described, though the
      combination with cerebrospinal fluid (CSF) leaks remains controversial. In this
      paper a case of a bilateral Mondini malformation with a CSF otorrhea on one side
      is reported. The malformed stapes contains a perforation in the middle of the
      footplate and associated thinning analogous to a pothole in a mountain stream.
      The histological findings support the hypothesis of pulsatile flow of CSF as
      origin of the perforation of the footplate.

PMID- 9166883
TI  - Circumferential squamocellular papilloma of the cervical esophagus, a rare cause
      of dysphagia. A case report.
AB  - A case report of a patient with circumferential benign squamous cell papilloma of
      the cervical esophagus is presented. The location, appearance and symptoms of the
      lesion are unusual, and the etiology and treatment are discussed. The case is
      important for otorhinolaryngologists, because the widely used method to examine
      the upper gastrointestinal tract, fiberesophagogastroscopy, does not offer
      optimum conditions to investigate the proximal esophagus. The rigid
      hypopharyngoesophagoscopy under general anesthesia is the method of choice for
      this region, a method familiar to otorhinolaryngologists.

PMID- 9166884
TI  - Bilateral pseudo-internuclear ophthalmoplegia in myasthenia gravis.
AB  - A 38-year-old male with bilateral pseudo-internuclear ophthalmoplegia (-INO) in
      myasthenia that could have been misdiagnosed as INO in multiple sclerosis is
      reported. He experienced fluctuating symptoms including double vision, imbalance,
      and tinnitus. His eye movements simulated bilateral INO, with a downshoot in
      abduction. After thymectomy, his eye movements became normal. From our case and a
      review of the literature, we propose that ptosis, downshoot, and fatigability are
      likely to be signs of pseudo-INO in myasthenia, whereas an impaired vertical
      smooth pursuit is unlikely. Dissociated nystagmus and monocular overshoot might
      be the results of central compensation.

PMID- 9166885
TI  - mRNA distribution and membrane localization of the OAT-K1 organic anion
      transporter in rat renal tubules.
AB  - OAT-K1, a renal organic anion transporter, which mediates methotrexate uptake,
      was analyzed for mRNA distribution along microdissected nephron segments and the
      immunolocalization in isolated plasma membranes from rat kidney. By using a
      reverse transcription-coupled PCR, OAT-K1 mRNA was detected predominantly in the
      superficial and juxtamedullary proximal straight tubules. Western blotting with
      antiserum for OAT-K1 revealed that the transporter protein with the apparent
      molecular mass of 40 kDa was expressed exclusively in the brush-border membranes
      from rat kidney. These findings suggest that the OAT-K1 is localized in the brush
      border membranes of the renal proximal straight tubules.

PMID- 9166886
TI  - Expression of recombinant human ceruloplasmin--an absolute requirement for
      splicing signals in the expression cassette.
AB  - We report the successful expression of recombinant human ceruloplasmin which was
      made possible by inclusion of splicing signals in the expression vector.
      Ceruloplasmin cDNA expressed from the vector pNUT in baby hamster kidney cells
      gave protein yields of 0.03 mg/l which increased to 15 mg/l with splicing signals
      present. The defect in expression from the intronless cDNA is due to complete
      retention of ceruloplasmin mRNA in cell nuclei. The block to cytoplasmic export
      is alleviated by splicing signals, allowing full expression of the mRNA.

PMID- 9166887
TI  - alpha1-beta interaction in voltage-gated cardiac L-type calcium channels.
AB  - The beta subunits of voltage-gated calcium channels normalize current amplitude,
      kinetics and voltage dependence of these channels by interacting with the
      channel's pore forming subunit alpha1. By screening an epitope expression library
      of alpha1Ca fusion proteins, a beta2a binding site of 22 amino acids was
      identified within the I-II cytoplasmic linker but not on other cytoplasmic
      sequences of alpha1Ca. This binding site overlaps by 14 amino acids with the
      conserved 18 amino acid peptide assumed to be essential for alpha1-beta
      interaction. The common 14 amino acid motif of alpha1Ca is sufficient to bind
      beta2a, and in addition beta1a, beta3 and beta4.

PMID- 9166888
TI  - Reconstitution of two isoforms of the human interleukin-11 receptor and
      comparison of their functional properties.
AB  - Long-term stable Ba/F3 transfectants (B13R alpha1 and B13R alpha2) expressing two
      isoforms of the human IL-IIR alpha receptor (alpha1 full length or alpha2 lacking
      the cytoplasmic domain) in combination with human gp130 were established. IL-11R
      alpha1 and IL-11R alpha2 were each expressed and detected as three bands upon
      Western blot analysis, with apparent molecular masses in agreement with those of
      the polypeptide backbone (47 and 44 kDa, respectively) with no, one or two N
      linked sugars. B13R alpha1 and B13R alpha2 bound IL-11-thioredoxin with similar
      efficiencies and proliferated with superimposable dose-response curves to IL-11,
      demonstrating that the intracellular domain of IL-11R alpha has no significant
      contribution on ligand binding and signaling. Analysis of a set of anti-human
      gp130 mAbs confirmed the similar responsiveness of B13R alpha1 and B13R alpha2
      transfectants.

PMID- 9166889
TI  - Spin trapping agent phenyl N-tert-butylnitrone protects against the onset of drug
      induced insulin-dependent diabetes mellitus.
AB  - Insulin-dependent diabetes mellitus is an autoimmune disease believed to be
      caused by an inflammatory process in the pancreas leading to selective
      destruction of the beta-cells. Cytokines and nitric oxide (NO) have been shown to
      be involved in this destruction. Phenyl N-tert-butylnitrone (PBN) has
      demonstrated protective effects against several pathological conditions including
      ischemia-reperfusion injury and endotoxin-induced shock. We report here that PBN
      co-administration can prevent the onset of the STZ-induced diabetes in mice. PBN
      co-treatment inhibited the streptozotocin (STZ)-induced hyperglycemia, the
      elevation in the level of glycated hemoglobin and weight loss in the treated
      mice. Histological observations indicated destruction of B-cells in the STZ
      treated animals and its prevention by PBN co-treatment. EPR spin trapping
      experiments in the pancreas indicated the in vivo formation of NO in STZ-treated
      animals and its attenuation by PBN treatment.

PMID- 9166890
TI  - Molecular cloning of hemocyanin cDNA from Penaeus vannamei (Crustacea, Decapoda):
      structure, evolution and physiological aspects.
AB  - Hemocyanin is present as 2 subunits in the hemolymph of Penaeus vannamei.
      Isolated from a hepatopancreas cDNA library of this penaeid shrimp, the cDNA
      chain (2095 bp) corresponds to a full length hemocyanin messenger as determined
      by Northern hybridization, with a short 5' untranslated region (17 bp), an open
      reading frame (1989 bp counting initiation and termination codons) coding for a
      signal peptide (13 residues) and a mature hemocyanin (648 amino acids), and a 3'
      untranslated region (89 bp) followed by the polyadenylated track. It is the first
      time that the existence of a hydrophobic signal peptide is shown in arthropod
      hemocyanin. Two primary N-terminal sequences are determined and a 3-fold increase
      of mRNA content, measured in the hepatopancreas during the premoult stages, is
      reported. The low level of polymorphism shown by P. vannamei hemocyanin, along
      with its weak percentage identity with counterparts and its similarity with
      hemocyanin from Panulirus interruptus, suggests that this arthropod hemocyanin
      may be a primitive subunit that has evolved independently, following gene
      duplication.

PMID- 9166891
TI  - A native electrostatic environment near Q(B) is not sufficient to ensure rapid
      proton delivery in photosynthetic reaction centers.
AB  - Flash-induced absorption spectroscopy has been used to characterize Rhodobacter
      capsulatus reaction centers mutated in the secondary quinone acceptor site (Q(B).
      We compared the wild-type, the L212Glu-L213Asp --> Ala-Ala photosynthetically
      incompetent double mutant (DM), and two photocompetent revertants, the DM+L217Arg
      --> Cys and the DM+M5Asn- --> Asp strains. The electrostatic environment for Q(B)
      is different in the two revertant strains. Only the L217Arg --> Cys mutation
      nearly restores the native electrostatic environment of Q(B)-. However, the level
      of recovery of the reaction center function, measured by the rates of second
      electron transfer and cytochrome c turnover, is quite incomplete in both strains.
      This shows that a wild-type-like electrostatic environment of Q(B)- cannot ensure
      on its own, rapid and efficient proton transfer to Q(B)-.

PMID- 9166893
TI  - Identification of novel heparin-binding domains of vitronectin.
AB  - Vitronectin is a multifunctional serum protein which provides a unique regulatory
      link between cell adhesion, humoral defense mechanism and the hemostatic system,
      and the heparin-binding properties of vitronectin are thought to have
      participated in various functional aspects. In addition to the carboxy-terminal
      glycosaminoglycan-binding motif, we report on two novel heparin-binding domains
      which were identified using phage display technique. One heparin-binding domain
      is located between amino acids Asp82 and Cys137 at the end of the connector
      region, while the other is in the second hemopexin-type repeat, between amino
      acids Lys175 and Asp219 of the vitronectin molecule. Our findings may shed new
      light to the activities of vitronectin and its binding to cells, which could not
      be explained solely on the basis of the known heparin-binding domain.

PMID- 9166892
TI  - Immune responses, not promoter inactivation, are responsible for decreased long
      term expression following plasmid gene transfer into skeletal muscle.
AB  - Long-term high-level in vivo gene expression appears to depend on the promoter
      chosen to drive the gene of choice. In many cases the promoter appears to 'switch
      off' some time after in vivo gene transfer. We demonstrate that, following
      intramuscular injection of beta-galactosidase reporter plasmids, promoter 'switch
      off' is due to elimination of fibres expressing the transferred reporter gene by
      activation of a Th1 (cytotoxic) immune response. This finding, in the absence of
      stimulation of the immune system by viral vector proteins, has implications not
      only for gene transfer experiments but for the future of muscle-directed gene
      therapy.

PMID- 9166894
TI  - Is an ATPase involved in uncoating of plasma membrane adaptor complex AP-2?
AB  - The coat of clathrin-coated vesicles mostly consists of clathrin and adaptor
      complexes AP-1 or AP-2. Clathrin is released from the vesicles in an ATP
      dependent fashion prior to their fusion with endosomes. In the present study we
      found that ATP strongly inhibits in vitro binding of cytosolic AP-2 to membranes
      of stripped vesicles, and promotes the release of endogenous AP-2 from clathrin
      deprived coated vesicles. Both effects required hydrolysis of ATP. In contrast,
      binding of AP-1 to stripped vesicles was not affected by ATP, but was enhanced by
      GTP-gamma-S. These results point to an ATPase that promotes the release of AP-2
      from clathrin-coated vesicles.

PMID- 9166895
TI  - Regulation of human renin secretion and gene transcription in Calu-6 cells.
AB  - Calu-6 cells were characterized for studying the transcriptional regulation of
      the human renin gene. Analysis of cis-acting elements of the renin promoter
      showed the highest activity within the first 582 bp in serum-free conditions and
      of the 892 bp in the presence of serum. cAMP activates renin mRNA synthesis
      parallel to renin production (20-fold increase) as well renin promoter activity
      (2-fold). cAMP response element and the (-77 to -67) element are both necessary
      for activation of the renin promoter but do not act independently. Functional
      analysis of Intron A revealed the presence of a silencer specific to renin
      producing cells.

PMID- 9166896
TI  - Comparative mutational analysis of peptidyl prolyl cis/trans isomerases: active
      sites of Escherichia coli trigger factor and human FKBP12.
AB  - A low degree of amino acid sequence similarity to FK506-binding proteins (FKBPs)
      has been obtained for the peptidyl prolyl cis/trans isomerase (PPIase) domain of
      E. coli trigger factor (TF) that was thought to be significant with regard to the
      enzymatic properties of the bacterial enzyme. We examined whether the alteration
      of a negatively charged side-chain at position 37 (FKBP numbering) and a
      phenylalanine at position 99, both highly conserved through both types of
      enzymes, leads to parallel effects on the catalytic activity of both FKBP12 and
      TF-PPIase domain in a series of tetrapeptide substrates with different P1
      subsites. For the latter enzyme, substitution of Glu178 by Val or Lys, which
      aligns to Asp37 in human FKBP12, enhanced the PPIase activity, whereas a strongly
      decreased enzymatic activity was determined for the Asp37Leu and Asp37Val
      variants of FKBP12. Regardless of the P1 subsite of the substrate used for the
      assay, mutation of Phe233Tyr generated a protein variant of the TF-PPIase domain
      with about 1% of the wild type PPIase activity. Dependent on the substrate
      nature, a moderate decrease as well as a 4.8-fold increase in k(cat)/K(M) could
      be determined for the corresponding Phe99Tyr FKBP12 variant. Neither of the
      mutations of the TF-PPIase domain was able to implant FK506 inhibition found as a
      major characteristic of the FKBP family of PPIases.

PMID- 9166898
TI  - Production of formyl-CoA during peroxisomal alpha-oxidation of 3-methyl-branched
      fatty acids.
AB  - alpha-Oxidation of 3-methyl-substituted fatty acids was studied in purified rat
      liver peroxisomes. The experiments revealed that formyl-CoA is formed during the
      alpha-oxidation process. The amount of formyl-CoA found constituted 2-5% of the
      amount of formate formed. Under the conditions used, no activation of exogenously
      added formate occurred in purified peroxisomes, whereas 95.5% of added synthetic
      formyl-CoA was converted to formate. These data indicate that during alpha
      oxidation first formyl-CoA is formed, which is then hydrolysed to formate.

PMID- 9166897
TI  - Functional characterization of the trout insulin promoter: implications for fish
      as a favorable model of pancreas development.
AB  - The complex anatomy of the mammalian pancreas, in which the endocrine cells are
      grouped in islets dispersed among the predominant exocrine component, has
      hampered study of the molecular events governing the development of pancreatic
      cell lineages. To investigate whether fish may provide relevant, complementary
      models of pancreas development, we characterized the trout insulin (tINS)
      promoter and its molecular interactions with PDX1, a key transcriptional and
      developmental factor of the mammalian pancreas. Transfection of a luciferase
      reporter plasmid containing the 280 bp 5'-flanking region of the tINS gene
      resulted in strong activity in mammalian pancreatic beta cells but not in CHO or
      pituitary cells. Footprinting assays and cotransfection experiments indicated
      that mammalian PDX1 binds to and activates the tINS promoter. By microinjecting
      plasmids to fertilized zebrafish eggs, we showed that the expression of mouse
      PDX1 is capable of activating the co-injected tINS promoter plasmid in most cell
      types of the 24-h zebrafish embryo. The conserved role of PDX1 in vertebrate
      insulin gene regulation opens the possibility to exploit fish models in the study
      of pancreas development.

PMID- 9166899
TI  - Isolation and characterization of heparin- and phosphorylcholine-binding proteins
      of boar and stallion seminal plasma. Primary structure of porcine pB1.
AB  - In the bovine, seminal plasma heparin-binding proteins bind to sperm lipids
      containing the phosphorylcholine group and mediate the capacitating effects of
      heparin-like glycosaminoglycans during sperm residence in the female genital
      tract. We report the characterization of heparin- and phosphorylcholine-binding
      proteins of stallion and boar seminal plasma. Horse seminal plasma proteins HSP-1
      and HSP-2, and boar protein pB1, belong to the same family as the bull heparin-
      and phosphorylcholine-binding proteins BSP-A1/2, BSP-A3, and BSP-30K. We have
      determined the amino acid sequence and posttranslational modifications of boar
      glycoprotein pB1. It contains 105 amino acids arranged into a mosaic structure
      consisting of a N-terminal 18-residue O-glycosylated polypeptide followed by two
      tandemly organized 40-45-residue fibronectin type II domains. pB1 displays 60-65%
      amino acid sequence similarity with its equine and bovine homologues. However, in
      their respective seminal plasmas, the BSP and the HSP proteins associate into 90
      150-kDa oligomeric complexes, whereas pB1 forms a 35-40-kDa complex with
      spermadhesin AQN-1. In addition, pB1 appears to be identical to the recently
      described leukocyte adhesion regulator of porcine seminal fluid pAIF-1. Our
      results tie in with the hypothesis that homologous proteins from different
      mammalian species may display distinct biological activities, which may be
      related to species-specific aspects of sperm physiology.

PMID- 9166900
TI  - Primary structures of two ribonucleases from ginseng calluses. New members of the
      PR-10 family of intracellular pathogenesis-related plant proteins.
AB  - The amino acid sequences of two ribonucleases from a callus cell culture of Panax
      ginseng were determined. The two sequences differ at 26% of the amino acid
      positions. Homology was found with a large family of intracellular pathogenesis
      related proteins, food allergens and tree pollen allergens from both
      dicotyledonous and monocotyledonous plant species. There is about 30% sequence
      difference with proteins from species belonging to the same plant order (Apiales:
      parsley and celery), 60% with those from four other dicotyledonous plant orders
      and about 70% from that of the monocotyledonous asparagus. More thorough
      evolutionary analyses of sequences lead to the conclusion that the general
      biological function of members of this protein family may be closely related to
      the ability to cleave intracellular RNA and that they have an important role in
      cell metabolism. As the three-dimensional structure of one of the members of this
      protein family has been determined recently [Gajhede et al., Nature Struct Biol 3
      (1996) 1040-1045], it may be possible to assign active-site residues in the
      enzyme molecule and make hypotheses about its mode of action. Structural features
      in addition to the cellular site of biosynthesis indicate that this family of
      ribonucleases is very different from previously investigated ones.

PMID- 9166901
TI  - Testosterone induces Ca2+ influx via non-genomic surface receptors in activated T
      cells.
AB  - Using the Fura-2 method we investigated a possible direct action of testosterone
      on cytosolic free calcium of splenic T cells isolated from female C57BL/10 mice.
      Testosterone at physiological concentrations of 1-10 nM induces an increase in
      [Ca2+]i within seconds, which is due to Ca2+ influx and not to Ca2+ release from
      intracellular stores. In contrast, estradiol induces both Ca2+ influx and Ca2+
      release. The testosterone-induced Ca2+ influx is mediated by Ni2+-blockable
      channels and is not inhibited by cyproterone, a blocker of the classical androgen
      receptor. Ca2+ influx can also be induced by testosterone conjugated to BSA which
      is impermeable to the plasma membrane. These data indicate a novel mode of direct
      action of testosterone on T cells which is not mediated through the classical
      androgen receptor response, but through unconventional plasma membrane receptors.

PMID- 9166902
TI  - GroES binding regulates GroEL chaperonin activity under heat shock.
AB  - Chaperonins GroEL14 and GroES7 are heat-shock proteins implicated in the
      molecular response to stress. Protein fluorescence, crosslinking and kinetic
      analysis revealed that the bond between the two otherwise thermoresistant
      oligomers is regulated by temperature. As temperature increased, the affinity of
      GroES7 and the release of bound proteins from the chaperonin concomitantly
      decreased. After heat shock, GroES7 rebinding to GroEL14 and GroEL14GroES7
      particles correlated with the restoration of optimal protein folding/release
      activity. Chaperonins thus behave as a molecular thermometer which can inhibit
      the release of aggregation-prone proteins during heat shock and restore protein
      folding and release after heat shock.

PMID- 9166903
TI  - The protein encoded by the MFT1 gene is a targeting factor for mitochondrial
      precursor proteins, and not a core ribosomal protein.
AB  - Yeast cells harboring mft1 mutations are compromised in mitochondrial protein
      targeting, and Mft1p has previously been identified as a ribosomal protein.
      However, two genes, PLC2 and YML062C, are present in the MFT1 locus, and we show
      that mft1 mutant cells are compromised in the function of the cytosolic protein
      encoded by YML062C. The ribosomal protein (YS3a) is actually encoded by the
      tightly linked PLC2 gene, and does not play a role in targeting proteins to the
      mitochondria.

PMID- 9166904
TI  - The cytosolic aldehyde dehydrogenase gene (Aldh1) is developmentally expressed in
      Leydig cells.
AB  - Cytosolic aldehyde dehydrogenase, ALDH1, participates in the oxidation of
      different aldehydes including that of all-trans retinal to retinoic acid. The
      accumulation of mouse Aldh1 transcripts is characterized by having different
      patterns in different tissues. This paper reports the greatest expression of
      Aldh1 in testis and liver. It was demonstrated that in testis, Aldh1 is
      specifically expressed in Leydig cells and is under developmental regulation. In
      vitro studies of cultured Leydig TM3 cells confirmed these results though such
      gene expression was found not to be mediated by LH regulation. Previous
      investigations have associated androgen receptors, and hence the androgen
      insensitivity syndrome in man, with the presence of ALDH1 in genital skin
      fibroblasts. However, this relationship was not established in a functional cell
      type, as is reported here for Leydig cells. These results could suggest a model
      for a molecular pathway from androgen receptor to retinoic acid biogenesis in
      Leydig cells via the mediation of ALDH.

PMID- 9166905
TI  - Modulation of the ER Ca2+ channel BCC1 from tendrils of Bryonia dioica by
      divalent cations, protons and H2O2.
AB  - Electrical properties of the ER Ca2+ channel BCC1 from tendrils of Bryonia dioica
      were analyzed after incorporation of BCC1 into black lipid bilayers. Single
      channel current fluctuations were modulated by divalent cations, protons and
      H2O2. Whereas the channel is permeable for Ca2+, Ba2+ and Sr2+, its conductance
      is strongly reduced in solutions containing MgCl2. Cu2+ and Zn2+ are potent
      inhibitors of BCC1 in micromolar concentrations. The open channel conductance of
      BCC1 increases with acidification of the electrolyte solution. H2O2 shows strong
      inhibitory effects on BCC1. The channel is almost completely closed at
      submillimolar concentrations of H2O2. The effects of pH and H2O2 on channel
      properties are directional and affect BCC1 at the Ca exit side, but not on the
      entry site. Thus, cytosolic pH and H2O2 levels may play an important role in the
      modulation of the cytoplasmic free calcium concentration through BCC1.

PMID- 9166906
TI  - Single molecular assay of individual ATP turnover by a myosin-GFP fusion protein
      expressed in vitro.
AB  - Fusion proteins of a truncated mutant of myosin subfragment-1 (S1dC) and green
      fluorescent protein (GFP) were expressed in vitro by T7 RNA polymerase and rabbit
      reticulocyte lysate. Single S1dC-GFP fusion proteins were clearly seen and their
      individual ATP turnovers were directly monitored using low background total
      internal reflection fluorescence microscopy (LBTIRFM), recently developed by our
      laboratory. LBTIRFM using GFP as a fluorescent tag allowed us to assay functions
      of single protein molecules expressed in vitro. Thus, the results suggested that
      this method may be particularly useful to analyze functions of proteins that
      cannot be produced in an active form and/or in large quantities in conventional
      heterologous expression systems.

PMID- 9166907
TI  - Leptin is a four-helix bundle: secondary structure by NMR.
AB  - Leptin is a signaling protein that in its mutant forms has been associated with
      obesity and Type II diabetes. The lack of sequence similarity has precluded
      analogies based on structural resemblance to known systems. Backbone NMR signals
      for mouse leptin (13C/15N -labeled) have been assigned and its secondary
      structure reveals it to be a four-helix bundle cytokine. Helix lengths and
      disulfide pattern are in agreement with leptin as a member of the short-helix
      cytokine family. A three-dimensional model was built verifying the mechanical
      consistency of the identified elements with a short-helix cytokine core.

PMID- 9166908
TI  - Role of modified glutamic acid in the helical structure of conantokin-T.
AB  - Circular dichroism (CD) and 2-dimensional NMR were used to study the solution
      conformation of conantokin-T (Con-T), a small peptide toxin found in the venom of
      fish-hunting cone snails, and its Glu-substituted analog. Con-T lacks disulfide
      bonds but contains many gamma-carboxyglutamic acids (Gla), a post-translationally
      modified residue. Our results show that Con-T adopts an alpha-helical
      conformation in aqueous solution even in the absence of calcium. Glu replacements
      diminish both helicity and function of Con-T. The helical content of Con-T is
      higher than most natural helical peptides of this length in aqueous solution. The
      sequence of this small toxin incorporates several known elements that stabilize
      alpha-helical structure in peptides. Gla residues form several salt bridges that
      stabilize helical conformation of Con-T.

PMID- 9166909
TI  - Development in neonatal rats of the sensory resetting of the locomotor rhythm
      induced by NMDA and 5-HT.
AB  - Developmental changes in the effects of quadriceps (Q) nerve stimulation on the
      locomotor rhythm induced by a mixture of N-methyl-D-aspartic acid and 5
      hydroxytryptamine were examined using in vitro preparations from neonatal rats at
      postnatal days (P) 1-6. The effects of such stimulation on the rhythm were
      dependent both on stimulus strength and on the age of the animal. Low-intensity
      stimulation (< or =3.0 x T, where T=threshold for the monosynaptic reflex) during
      the flexor phase reset the rhythm via a prolongation of the flexor burst in most
      rats at P1-3, but via flexor burst truncation at P4-6. At any age, low-intensity
      stimulation during the extensor phase had no consistent effect on the ongoing
      rhythm. Activation of muscle afferents evoked via isometric contraction of the Q
      muscle caused effects similar to those obtained on low-intensity electrical
      stimulation in all age groups. In all age groups, high-intensity stimulation (>
      or =5.0 x T) caused resetting when delivered during the flexor phase via a
      prolongation of the flexor burst and during the extensor phase via a truncation
      of the extensor burst. These results suggest that the type of resetting evoked
      from low-threshold muscle afferents changes drastically during postnatal weekl,
      while effects evoked from high-threshold afferents remain unchanged.

PMID- 9166910
TI  - Reciprocal changes in expression of mRNA for nerve growth factor and its
      receptors TrkA and LNGFR in brain of aged rats in relation to maze learning
      deficits.
AB  - Quantitative in situ hybridization was used to examine the expression of mRNA for
      nerve growth factor (NGF) and its receptors, p140Trk (TrkA) and p75LNGFR (LNGFR),
      in different brain regions of adult (3-month-old) and aged (27-month-old) Wistar
      rats. The brain regions studied were hippocampus (dentate gyrus, CA3 region),
      basal forebrain (medial septum, diagonal band) and caudate-putamen. Prior to
      hybridization histochemistry behaviorally impaired as well as severely impaired
      animals were selected from a large group of old rats according to their
      performance in the Morris water maze. The impaired rats showed longer escape
      latencies and, thus, implicitly impaired performance in the place version of the
      task, but did not differ from adult controls on the platform crossing measure
      registered during the spatial probe trial. The severely impaired rats were
      significantly impaired on both measures, both in comparison with the adult
      animals and in comparison with the impaired aged rats. Inspection of the
      hippocampus revealed no age- or performance-related changes in NGF mRNA levels.
      The overall expression of TrkA mRNA in basal forebrain and caudate was found to
      be decreased in the impaired (-20%) as well as the severely impaired aged rats (
      17%). A significant increase in p75LNGFR mRNA was found in the basal forebrain of
      the impaired rats in comparison with the severely impaired aged rats (+35%) and
      adult animals (+33%). These findings show that age-related maze performance
      deficits are accompanied by a decrease in basal forebrain and striatal TrkA mRNA
      expression. The increase in basal forebrain LNGFR mRNA levels observed in
      impaired, but not severely impaired, aged rats may reflect an early manifestation
      of processes underlying age-related cognitive deficits and may constitute a
      restorative and/or compensatory mechanism, since these rats displayed fewer
      deficits in navigation of the maze.

PMID- 9166911
TI  - Voluntary head stabilization in space during oscillatory trunk movements in the
      frontal plane performed in weightlessness.
AB  - The ability voluntarily to stabilize the head in space during lateral rhythmic
      oscillations (0.59+/-0.09 Hz) of the trunk has been investigated during
      microgravity (microG) and normal gravity (nG) conditions (parabolic flights).
      Five healthy young subjects, who gave informed consent, were examined. The
      movements were performed with eyes open or eyes closed, during phases of either
      microG or nG. The main result was that head orientation with respect to vertical
      may be stabilized about the roll axis under microG with, as well as without
      vision, despite the reduction in vestibular afferent and muscle proprioceptive
      inputs. Moreover, the absence of head stabilization about the yaw axis confirms
      that the degrees of freedom of the neck can be independently controlled, as was
      previously reported. These results seem to indicate that voluntary head
      stabilization does not depend crucially upon static vestibular afferents. Head
      stabilization in space may in fact be organized on the basis of either dynamic
      vestibular afferents or a short-term memorized postural body schema.

PMID- 9166912
TI  - Influence of object position and size on human prehension movements.
AB  - Prehension movements of the right hand were recorded in normal subjects using a
      computerized motion analyzer. The kinematics and the spatial paths of markers
      placed at the wrist and at the tips of the index finger and thumb were measured.
      Cylindrical objects of different diameters (3, 6, 9 cm) were used as targets.
      They were placed at six different positions in the workspace along a circle
      centered on subject's head axis. The positions were spaced by 10 degrees starting
      from 10 degrees on the left of the sagittal axis, up to 40 degrees on the right.
      Both the transport and the grasp components of prehension were influenced by the
      distance between the resting hand position and the object position. Movement
      time, time to peak velocity of the wrist and time to maximum grip aperture varied
      as a function of distance from the object, irrespective of its size. The
      variability of the spatial paths of wrist and fingers sharply decreased during
      the phase of the movement prior to contact with the object. This indicates that
      the final position of the thumb and the index finger is a controlled parameter of
      visuomotor transformation during prehension. The orientation of the opposition
      axis (defined as the line connecting the tips of the thumb and the index finger
      at the end of the movement) was measured. Several different frames of reference
      were used. When an object-centered frame was used, the orientation of the
      opposition axis was found to change by about 10 degrees from one object position
      to the next. By contrast, when a body-centered frame was used (with the head or
      the forearm as a reference), this orientation was found to remain relatively
      invariant for different object positions and sizes. The degree of wrist flexion
      was little affected by the position of the object. This result, together with the
      invariant orientation of the opposition axis, shows that prehension movements
      aimed at cylindrical objects are organized so as to minimize changes in posture
      of the lower arm.

PMID- 9166913
TI  - Prehension of objects oriented in three-dimensional space.
AB  - When reaching for an object, the proximity of the object, its orientation, and
      shape should all be correctly estimated well before the hand arrives in contact
      with it. We were interested in the effects of the object's orientation on manual
      prehension. Subjects were asked to reach for an object at one of several possible
      orientations. We found that the trajectory of the hand and its rotation and
      opening were significantly affected by the object's orientation within the first
      half of the movement. We also detected a slight delay of the wrist relative to
      the forearm and a small bias of the orientation of the fingers' tips toward the
      orientation of the table on which the object lay. Finally, the aperture of the
      hand was proportional to the physical size of the object, which shows that size
      constancy was achieved from the variation of the object's orientation. Taken
      together, these results indicate that the three components of the movement - the
      transport, rotation, and opening of the hand - have access to a common visual
      representation of the object's orientation.

PMID- 9166914
TI  - Is human muscle spindle afference dependent on perceived size of error in visual
      tracking?
AB  - Impulses of 16 muscle spindle afferents from finger extensor muscles were
      recorded from the radial nerve along with electromyographic (EMG) activity and
      kinematics of joint movement. Twelve units were classified as Ia and 4 as II
      spindle afferents. Subjects were requested to perform precision movements at a
      single metacarpophalangeal joint in an indirect visual tracking task. Similar
      movements were executed under two different conditions, i.e. with high and low
      error gain. The purpose was to explore whether different precision demands were
      associated with different spindle firing rates. With high error gain, a small but
      significantly higher impulse rate was found in pooled data from Ia afferents
      during lengthening movements but not during shortening movements, nor with II
      afferents. EMG was also significantly higher with high error gain in recordings
      with Ia afferents. When the effect of EMG was factored out, using partial
      correlation analysis, the significant difference in Ia firing rate vanished. The
      findings suggest that fusimotor drive as well as skeletomotor activity were both
      marginally higher when the precision demand was higher, whereas no indication of
      independent fusimotor adjustments was found. These results are discussed with
      respect to data from behaving animals and the role of fusimotor independence in
      various limb muscles proposed.

PMID- 9166915
TI  - Conditioned and unconditioned forelimb reflex systems in the cat: involvement of
      the intermediate cerebellum.
AB  - Temporary inactivation of the cerebellar interposed nuclei was used to assess the
      role of the intermediate cerebellum in the performance of forelimb cutaneo
      muscular reflexes in the cat. The following types of reflexive responses were
      evaluated: the classically conditioned and unconditioned forelimb withdrawal
      responses and the forelimb tactile placing, hopping and magnet responses. The
      experiments tested the hypothesis that the intermediate cerebellum is involved in
      the performance of all the above forelimb reflexes. The forelimb withdrawal
      reflex was classically conditioned in a newly developed paradigm in which animals
      were first operantly conditioned to stand on four elevated platforms. Trained
      animals were microinjected with a gamma-aminobutyric acid (GABA) agonist,
      muscimol, in the interposed nuclei, and the effects of inactivation of the
      intermediate cerebellar output on the forelimb reflexes were examined. The main
      findings of these experiments are that unilateral muscimol inactivation of the
      interposed nuclei in the cat abolished the expression of the classically
      conditioned limb flexion reflex, suppressed the performance of the unconditioned
      withdrawal reflex and, in parallel, down-regulated the tactile placing, hopping
      and magnet postural responses in the ipsilateral forelimb. These observations are
      inconsistent with concepts indicating exclusive involvement of the intermediate
      cerebellum in the classically conditioned reflexes elicited by aversive stimuli.
      On the contrary, they support the hypothesis of a more global involvement of this
      structure in learned and unlearned defensive flexion reflexes and in automatic
      postural response systems.

PMID- 9166916
TI  - N-methyl-D-aspartate enhancement of phasic responses in primate neocortex.
AB  - In area 17 of the awake macaque, disinhibition by blockade of GABA(A) receptors
      results in a marked elevation in neuronal excitability, with a particular focus
      in the supragranular laminae. We examined the possibility that the excitatory
      supragranular response is N-methyl-D-aspartate (NMDA)-mediated. Laminar activity
      profiles consisting of flash-evoked field potential, current source density (CSD)
      and multiunit activity (MUA) measures were obtained during striate cortex
      penetrations using multicontact electrodes that incorporated single or double
      microinjection cannulae. Profiles were recorded before and at successive time
      points after bicuculline induction of disinhibition. Both the noncompetitive NMDA
      antagonist MK-801 and the competitive antagonist APV reversed bicuculline
      effects, producing a normal laminar activity profile. NMDA-mediated enhancement
      of excitatory responses in the supragranular laminae of neocortex is believed to
      play a role in normal signal processing, as well as in epileptic manifestations.

PMID- 9166918
TI  - P300-like potential disappears in rabbits with lesions in the nucleus basalis of
      Meynert.
AB  - The nucleus basalis of Meynert (nbM, substantia innominata) in the basal
      forebrain provides a single major source of cholinergic innervation for the
      entire cerebral cortex. We tested the effects of nbM lesions on rabbit P300-like
      potentials. The P300-like event-related potential (ERP) was recorded in 14 female
      adult white rabbits using a conventional auditory oddball paradigm. The
      probability of occurrence for the 2-kHz and 1-kHz stimulus tones was 90%
      (frequent) and 10% (rare), respectively. The nbM was destroyed bilaterally in
      seven rabbits referred to as the nbM (+) group. In the other seven rabbits [nbM (
      ) group], putamen nuclei (n=6) or amygdaloid nuclei (n=1) were destroyed
      bilaterally. The evoked responses were recorded before and 1 week after the
      destruction. In the nbM (+) group, P300 amplitude to rare stimuli significantly
      decreased after the lesion. In the nbM (-) group, no component of ERPs showed
      changes after the lesions. These results indicate that the nbM might be involved
      in the generation of the rabbit P300.

PMID- 9166917
TI  - Failure in learning task and loss of cortical cholingergic fibers in microsphere
      embolized rats.
AB  - The present study was undertaken to elucidate the pathological changes in
      learning and memory functions and in the metabolism of cortical cholinergic
      neurons following microsphere embolism in the rat. Microspheres (48 microm) were
      injected into the right internal carotid artery of rats. Learning and memory
      functions were measured 7 or more days after the embolism by active and passive
      avoidance, and water maze tasks. In the biochemical study, cortical acetylcholine
      and choline contents, and choline acetyltransferase activity were measured.
      Cortical acetylcholinesterase-containing fibers were quantitatively estimated in
      the embolized rat. The active and passive avoidance, and water maze tasks were
      impaired in the microsphere-embolized rat. In the histochemical study, the
      density of cortical acetylcholinesterase-containing fibers of the ipsilateral
      hemisphere of the microsphere-embolized rat was decreased, but cell density was
      unchanged. Furthermore, microsphere embolism decreased the cortical acetylcholine
      concentration and choline acetyltransferase activity and increased the choline
      concentration. The results suggest that microsphere embolism causes severe damage
      to cortical cholinergic neurons, which may be, at least in part, related to the
      impairment of learning and memory functions in the sustained brain ischemia.

PMID- 9166919
TI  - The coding of head orientations in neurons of bilateral vestibular nuclei of cats
      after unilateral labyrinthectomy: response to off-vertical axis rotation.
AB  - In decerebrate cats that had been acutely hemilabyrinthectomized (HL), the
      extracellular activities of vestibular nuclear neurons on the lesioned and
      labyrinth-intact sides were studied during constant-velocity off-vertical axis
      rotations (OVAR) in the clockwise (CW) and counterclockwise (CCW) directions (at
      10 degrees tilt). Over the range of 1.75-15 degrees/s, two types of neuronal
      responses were identified on both sides. Some neurons showed symmetric and
      velocity-stable bidirectional response sensitivity (delta defined as the CW gain
      over the CCW gain) while other neurons exhibited asymmetric and velocity-variable
      delta. The mathematically derived gain tuning ratios of these two groups of
      neurons were within the range of one-dimensional and two-dimensional neurons
      respectively. The best response orientations in one-dimensional neurons and the
      orientations of the maximum response vector, S(max), in two-dimensional neurons
      were found to point in all directions on the horizontal plane. On the labyrinth
      intact side, both the one-dimensional and two-dimensional neurons showed
      asymmetry in the neuron numbers and/or the response gains between the two roll
      quadrants as well as between the two pitch quadrants. In addition, both the
      neuron number and gain were significantly higher for neurons in the head
      down/ipsilateral-side-down half-circle than those in the head-up/contralateral
      side-down half-circle. None of the aforementioned asymmetries was observed on the
      lesioned side. That a comparable pattern of distribution was observed in the one
      dimensional and two-dimensional neurons suggests that these neurons maintain a
      common spatial reference frame in encoding head orientational signals arising
      from the ipsilateral and contralateral otoliths. Furthermore, a predominance of
      two-dimensional neurons that exhibited a greater gain with CW rotations was
      observed on both sides of HL cats. Of the response dynamics observed amongst
      neurons on the two sides of HL cats, no difference was found with regard to the
      response gain and the pattern of response lead. However, a difference in response
      lag was observed between neurons on the two sides of HL cats. These suggest that
      there is a segregation of otolithic signals to reach the ipsilateral and
      contralateral vestibular nuclei. Taken together, the present study demonstrates
      that one-dimensional and two-dimensional neuronal responses could be elicited
      with inputs arising solely from the ipsilateral or contralateral otoliths. The
      observed orientational tuning and the CW-CCW asymmetry to bidirectional rotation
      may provide the essential directional coding of head orientations. Further, the
      imbalance of spatial/dynamic response patterns between the bilateral vestibular
      nuclei following the restriction of otolith inputs by HL implies that converging
      otolithic inputs from the bilateral labyrinths are essential for producing the
      neuronal responses in control animals. The results are also discussed in terms of
      the possible contribution of the various neural asymmetries between neuronal
      subpopulations in the bilateral vestibular nuclei to the behavioral symptoms
      accompanying acute HL.

PMID- 9166920
TI  - The human horizontal vestibulo-ocular reflex during combined linear and angular
      acceleration.
AB  - We employed binocular magnetic search coils to study the vestibulo-ocular reflex
      (VOR) and visually enhanced vestibulo-ocular reflex (VVOR) of 15 human subjects
      undergoing passive, whole-body rotations about a vertical (yaw) axis delivered as
      a series of pseudorandom transients and sinusoidal oscillations at frequencies
      from 0.8 to 2.0 Hz. Rotations were about a series of five axes ranging from 20 cm
      posterior to the eyes to 10 cm anterior to the eyes. Subjects were asked to
      regard visible or remembered targets 10 cm, 25 cm, and 600 cm distant from the
      right eye. During sinusoidal rotations, the gain and phase of the VOR and VVOR
      were found to be highly dependent on target distance and eccentricity of the
      rotational axis. For axes midway between or anterior to the eyes, sinusoidal gain
      decreased progressively with increasing target proximity, while, for axes
      posterior to the otolith organs, gain increased progressively with target
      proximity. These effects were large and highly significant. When targets were
      remote, rotational axis eccentricity nevertheless had a small but significant
      effect on sinusoidal gain. For sinusoidal rotational axes midway between or
      anterior to the eyes, a phase lead was present that increased with rotational
      frequency, while for axes posterior to the otolith organs phase lag increased
      with rotational frequency. Transient trials were analyzed during the first 25 ms
      and from 25 to 80 ms after the onset of the head rotation. During the initial 25
      ms of transient head rotations, VOR and VVOR gains were not significantly
      influenced by rotational eccentricity or target distance. Later in the transient
      responses, 25-80 ms from movement onset, both target distance and eccentricity
      significantly influenced gain in a manner similar to the behavior during
      sinusoidal rotation. Vergence angle generally remained near the theoretically
      ideal value during illuminated test conditions (VVOR), while in darkness vergence
      often varied modestly from the ideal value. Regression analysis of instantaneous
      VOR gain as a function of vergence demonstrated only a weak correlation,
      indicating that instantaneous gain is not likely to be directly dependent on
      vergence. A model was proposed in which linear acceleration as sensed by the
      otoliths is scaled by target distance and summed with angular acceleration as
      sensed by the semicircular canals to control eye movements. The model was fit to
      the sinusoidal VOR data collected in darkness and was found to describe the major
      trends observed in the data. The results of the model suggest that a linear
      interaction exists between the canal and otolithic inputs to the VOR.

PMID- 9166921
TI  - Blockade of serotonin-2C receptors by mesulergine reduces ocular dominance
      plasticity in kitten visual cortex.
AB  - We have investigated the role of serotonin-2C (5-HT2C) receptors in modulation of
      ocular dominance plasticity in kitten visual cortex. A small quantity of the 5
      HT2C receptor blocker, mesulergine, was infused into the visual cortex of one
      hemisphere of 5- to 7-week-old kittens using osmotic minipumps, while the control
      hemisphere received vehicle solution. At the same time, one eyelid of the
      experimental animals was sutured shut. The ocular dominance distributions in the
      visual cortex (area 17) were assessed using extracellular recording methods after
      1 week of combined mesulergine infusion and monocular deprivation. We found that
      the majority of the neurons remained binocularly responsive in the mesulergine
      treated hemisphere, while most of the neurons recorded were either unresponsive
      or only weakly responsive to the deprived eye in the control hemisphere. Local
      infusion of mesulergine into the kitten visual cortex thus reduced the shift of
      ocular dominance that normally occurs in animals of these ages following
      monocular deprivation. The blocking effect seems to be distance-dependent and
      therefore dose-dependent: the farther away the recording sites were from the
      injection site, the fewer binocularly responsive cells were found. These results
      are relevant to previous findings indicating transient overexpression of 5-HT2C
      receptor in visual cortex of kittens at these ages. The data suggest that the 5
      HT2C receptor system may be involved in the formation and modification of ocular
      dominance columns in the developing visual cortex.

PMID- 9166922
TI  - Input-output properties and gain changes in the human corticospinal pathway.
AB  - Experiments were done to determine the form of the input-output relation (i.e.
      stimulus intensity vs response amplitude) of the corticospinal pathway of the
      first dorsal interosseous and the tibialis anterior, respectively. Our purpose
      was to determine from these quantitative relations which input-output parameters
      would be useful measures in studies dealing with motor cortical task dependence.
      The motor cortex was excited by focal transcranial magnetic stimuli and the
      evoked motor response were recorded with surface electromyographic electrodes. In
      some experiments the discharge probability of single motor units in response to
      magnetic stimuli of increasing intensity was determined from intramuscular
      recordings. For both muscles the form of the input-output relation was sigmoidal.
      The steepness of the relation increased, up to 4-7 times the value at rest, with
      increasing tonic background activity. The threshold decreased, but only slightly,
      with increasing tonic background activity. The minimum value of the threshold was
      reached at activation levels of about 10-20% of the maximum tonic effort, whereas
      the steepness of the relation reached its maximum at higher activation levels,
      typically about 30-40% of the maximum tonic effort. These observations imply that
      these two input-output parameters of the corticospinal pathway - one reflecting
      the bias level (threshold) and the other the gain (slope) - are determined by
      different neural mechanisms. The plateau level of the sigmoidal input-output
      relation was not influenced by the background activation level, except that in
      some subjects (4/9) it could not be reached when no background motor activity was
      present. This was probably due, for the most part, to limitation of the maximum
      stimulator output. Additionally, this finding may reflect a change in the
      intrinsic excitability of the motor cortex in going from rest to activity, or
      that convergent inputs from different descending and afferent systems are
      required for maximal activation of motoneuron pools. Thus, the threshold,
      steepness and plateau level characterize the input-output parameters of the human
      corticospinal pathway for a given level of motor activity. In contrast to the
      nonlinear input-output relation of the corticospinal pathway as whole, which
      includes the motoneuron pool and any spinal interneuronal relays, the discharge
      probability of all single motor units was a linearly increasing function of the
      stimulus strength (r> or =0.9, P<0.01). Thus, the sigmoidal input-output relation
      of the corticospinal pathway, as a whole, is not due to the input-output
      properties of single motoneurons. The possible neural mechanisms which underlie
      the shape and parameters of the input-output relation as well as the
      methodological implications of the results are considered.

PMID- 9166923
TI  - Effects of spatial attention on directional manual and ocular responses.
AB  - The aim of the present study was to investigate how spatial attention influences
      directional manual and saccadic reaction times. Two experiments were carried out.
      In experiment 1 subjects were instructed to perform pointing responses toward
      targets that were located either in the same or the opposite hemifield with
      respect to the hemifield in which an imperative stimulus was presented. In
      experiment 2, they were instructed to make saccadic or pointing responses. The
      direction of the responses was indicated by the shape of the imperative stimulus.
      Reaction time (RT), movement time, and, in experiment 2, saccadic trajectory were
      measured. The imperative stimulus location was either cued (endogenous attention)
      or uncued. In the latter case the imperative stimulus presentation attracted
      attention (exogenous attention). The main results of the experiments were the
      following: First, exogenous attention markedly decreased the RTs when the
      required movement was directed toward the imperative stimulus location. This
      directional effect was much stronger for pointing than for ocular responses.
      Second, endogenously allocated attention did not influence differentially RTs of
      pointing responses directed toward or away the attended hemifield. In contrast,
      endogenous attention markedly favored the saccadic responses when made away from
      the cued hemifield. Third, regardless of cueing, the direction of movement
      affected both pointing and saccadic reaction times. Saccadic reaction times were
      faster when the required movement was directed upward, while manual reaction
      times were faster when the movement was directed downward. Fourth, lateralized
      spatial attention deviated the trajectory of the saccades contralateral to the
      attention location. This pattern of results supports the notion that spatial
      attention depends on the activation of the same sensorimotor circuits that
      program actions in space.

PMID- 9166924
TI  - Topography and dipole analysis of reafferent electrical brain activity following
      the Bereitschaftspotential.
AB  - The cerebral events related to limb movements can be studied noninvasively with
      the method of evoked potentials. In this study, a brain potential is analysed
      that follows the onset of a simple finger movement. Because this potential
      occurred after active as well as after passive movements, its previously alleged
      reafferent somatosensory nature is confirmed in this study. Detailed topographic
      analysis revealed that this potential has the same polarity and merges with the
      preceeding Bereitschaftspotential (BP; in the active movement) at central
      electrodes, whereas at parietal electrodes polarity is opposite to the BP. In
      individual subjects, the maximum of the BP and the peak of the reafferent
      potential are separated by a small gap, previously described as pre-motion
      positivity. A comparison with the N20 potential of the electrically evoked
      somatosensory potential showed similar potential topography, albeit opposite
      polarity. The dipole analysis supported the view that the reafferent and the
      electrically evoked potentials are likely to arise from the same cortical area,
      namely the primary somatosensory cortex.

PMID- 9166925
TI  - Feedforward contraction of transversus abdominis is not influenced by the
      direction of arm movement.
AB  - Because the structure of the spine is inherently unstable, muscle activation is
      essential for the maintenance of trunk posture and intervertebral control when
      the limbs are moved. To investigate how the central nervous system deals with
      this situation the temporal components of the response of the muscles of the
      trunk were evaluated during rapid limb movement performed in response to a visual
      stimulus. Fine-wire electromyography (EMG) electrodes were inserted into
      transversus abdominis (TrA), obliquus internus abdominis (OI) and obliquus
      externus abdominis (OE) of 15 subjects under the guidance of real-time ultrasound
      imaging. Surface electrodes were placed over rectus abdominis (RA), lumbar
      multifidus (MF) and the three parts of deltoid. In a standing position, ten
      repetitions of shoulder flexion, abduction and extension were performed by the
      subjects as fast as possible in response to a visual stimulus. The onset of TrA
      EMG occurred in advance of deltoid irrespective of the movement direction. The
      time to onset of EMG activity of OI, OE, RA and MF varied with the movement
      direction, being activated earliest when the prime action of the muscle opposed
      the reactive forces associated with the specific limb movement. It is postulated
      that the non-direction-specific contraction of TrA may be related to the control
      of trunk stability independent of the requirement for direction-specific control
      of the centre of gravity in relation to the base of support.

PMID- 9166926
TI  - Symmetric force response of human masticatory muscles to stretch and unloading.
AB  - During chewing, the force exerted by the jaw-closing muscles must constantly
      adapt to changing resistances between the teeth, as the food is broken down. In
      the present study, the changes in biting force resulting from small, controlled
      displacements imposed on isometrically contracting jaw-closing muscles were
      measured. We found that the force changes resulting from small loading and
      unloading movements were normally highly symmetrical. The initial force change
      was linear, and preceded the onset of reflex changes in muscle activity. Later
      changes in force were the result of both short- and long-latency reflexes in the
      jaw-closing muscles, the long-latency component being quantitatively greater. The
      long-latency unloading reflex in the jaw-closing muscles has not been described
      hitherto. The symmetry of force increase with loading and decrease with unloading
      was absent in one subject with atypical stretch and H-reflexes.

PMID- 9166927
TI  - Waveform complexity of unit activity recorded with concentric needle electrodes
      from human peripheral nerves.
AB  - Using standardised concentric needle electrodes 170 single units were recorded
      from myelinated cutaneous afferents in the human median or ulnar nerves. The
      unitary waveforms were of four types: single-peaked monophasic potentials (type
      I), double-peaked monophasic potentials (type II), biphasic potentials (type III)
      and triphasic potentials (type IV). Type II and IV occurred more frequently than
      the other types. Units of different functional classes had similar waveforms and
      there was no specific type of waveform distribution in any particular unit
      category. In some recording situations there were changes in unitary waveforms
      from one type to another. There was a tendency for the complex type IV, type III
      and type II waveforms to change to the simple type I. Adjustment of the electrode
      often provoked such waveform changes. The waveform profiles and waveform changes
      observed during recordings with concentric needles were significantly different
      from those encountered with conventional tungsten electrodes, which might be due
      to differences in recording properties between the two electrodes. Possible
      neural mechanisms underlying the observed waveforms and waveform transitions are
      discussed. In particular, our data suggest that concentric needle electrodes
      record single-unit activity from myelinated fibres extracellularly.

PMID- 9166928
TI  - Is the erect posture in microgravity based on the control of trunk orientation or
      center of mass position?
AB  - In the present experiments carried out in microgravity two questions were
      addressed. First, when the subject was instructed to adopt a vertical erect
      posture in microgravity with his feet fixed to the floor of the space cabin,
      would he control anteroposterior position with respect to the ankle joint axis of
      the "vertical projection" of his center of mass (CM) or trunk axis orientation
      with respect to the "vertical" (perpendicular to the floor of the space cabin)?
      Secondly, is CM anteroposterior position regulated during upper trunk movements
      in microgravity, in the absence of equilibrium constraint? Two subjects were
      tested in a long-term space flight. Video camera recordings were performed and
      analyzed off line. The results show that during erect vertical posture in
      microgravity, the trunk axis with respect to the "vertical" is inclined some 7
      degrees forward. The anteroposterior position of the CM "vertical" projection is
      not shifted forward, as might be expected in view of the trunk inclination, but
      remains close to the ankle joint axis. At the end of the upper trunk forward or
      backward bending movement, the final position of the vertical CM projection
      remains close to the ankle joint axis in microgravity. These results are
      interpreted as indicating that CM anteroposterior position continues to be
      accurately controlled in microgravity; the forward inclination of the trunk axis
      observed in microgravity is interpreted as being due to a misevaluation of the
      "vertical" axis on the basis of biased information from proprioceptive inputs.

PMID- 9166929
TI  - Human intramuscular and cutaneous pain: psychophysical comparisons.
AB  - We used psychophysical methods to compare the central processing of nociceptive
      inputs from skin and muscle in ten normal humans. Both intramuscular electrical
      and infrared CO2 laser cutaneous stimulation showed increasing but decelerating
      (downward concave) stimulus-response curves and similar temporal summation
      characteristics. Intramuscular stimulation was rated significantly more
      unpleasant than cutaneous stimulation. The results are consistent with a common
      mode of central nociceptive processing for skin and muscle pain intensity but
      suggest a relatively larger activation of affective mechanisms by muscle
      afferents.

PMID- 9166930
TI  - Recurrent gains of 1q, 8 and 12 in the Ewing family of tumours by comparative
      genomic hybridization.
AB  - Comparative genomic hybridization (CGH) was used to detect copy number changes of
      DNA sequences in the Ewing family of tumours (ET). We analysed 20 samples from 17
      patients. Fifteen tumours (75%) showed copy number changes. Gains of DNA
      sequences were much more frequent than losses, the majority of the gains
      affecting whole chromosomes or whole chromosome arms. Recurrent findings included
      copy number increases for chromosomes 8 (seven out of 20 samples; 35%), 1q (five
      samples; 25%) and 12 (five samples; 25%). The minimal common regions of these
      gains were the whole chromosomes 8 and 12, and 1q21-22. High-level amplifications
      affected 8q13-24, 1q and 1q21-22, each once. Southern blot analysis of the
      specimen with high-level amplification at 1q21-22 showed an amplification of FLG
      and SPRR3, both mapped to this region. All cases with a gain of chromosome 12
      simultaneously showed a gain of chromosome 8. Comparison of CGH findings with
      cytogenetic analysis of the same tumours and previous cytogenetic reports of ET
      showed, in general, concordant results. In conclusion, our findings confirm that
      secondary changes, which may have prognostic significance in ET, are trisomy 8,
      trisomy 12 and a gain of DNA sequences in 1q.

PMID- 9166931
TI  - Induction of p16 during immortalization by HPV 16 and 18 and not during malignant
      transformation.
AB  - The p16 (MTS1) tumour-suppressor gene is a cyclin-dependent kinase (cdk)
      inhibitor that decelerates the cell cycle by inactivating the cdks that
      phosphorylate the retinoblastoma tumour-suppressor gene (Rb) protein (pRb). In
      cervical cancers, pRb is inactivated by the HPV E7 oncoprotein or by mutations.
      The hypothesis of earlier reports was that the disruption of the p16/cdk
      cyclin/Rb cascade is essential for malignant cervical
      transformation/carcinogenesis. We previously established in vitro model systems
      of cervical cancer representing four steps of oncogenic progression initiated by
      the two most common oncogenic HPVs in ectocervical and endocervical epithelial
      cells. This report used these systems to investigate the role of p16 in cervical
      cancers. A dramatic enhancement of the p16 RNA level was observed after
      immortalization by HPV 16 or 18. Furthermore, the p16 protein was newly observed
      following immortalization. However, no further changes were found for RNA or
      protein levels after serum selection or malignant transformation. For three
      cervical carcinoma cell lines, similar high levels of p16 expression were seen.
      Point mutations or homozygous deletions of p16 were not observed in the in vitro
      systems or in clinical specimens. These results suggest that the inactivation of
      the p16/cdk-cyclin/Rb cascade does not occur during malignant transformation but
      occurs during the immortalization by HPV in HPV-harbouring premalignant lesions,
      the in situ equivalent of immortalized cells. Also suggested is that p16 has no
      role in the specific malignant transformation step from immortal premalignant
      lesions during the carcinogenesis of HPV-initiated cervical cancers.

PMID- 9166932
TI  - Comparison of delta-aminolaevulinic acid and its methyl ester as an inducer of
      porphyrin synthesis in cultured cells.
AB  - This study was carried out to test the hypothesis that induction of intracellular
      porphyrin synthesis by delta-aminolaevulinic acid (ALA) used to sensitize cells
      in photodynamic therapy would be more efficient if the ALA was used in an
      esterified form. Contrary to expectation, the generation of tetrapyrroles (TP) by
      cultured epithelial cells (CNCM-I-221) exposed to equimolar concentrations (0.6
      mM) of ALA or its methyl ester (ALA-ME) showed that the mean total TP production
      rate during 6 h incubation in serum-free medium was 0.13 fmol cell(-1) h(-1) for
      ALA-exposed cells compared with 0.04 fmol cell(-1) h(-1) for cells exposed to ALA
      ME. Fluorescein diacetate uptake and conversion to fluorescein indicated
      intracellular non-specific esterase activity, implying that ALA-ME conversion to
      ALA can occur. Cells exposed to ALA-ME exhibited loss of a greater proportion of
      total tetrapyrroles in the form of extracellular protoporphyrin IX (PPIX; 22.8%)
      compared with 11.6% in ALA-treated cells with a corresponding reduction in cell
      associated PPIX (P < 0.05). A variable initial elevation in haem levels in ALA-ME
      treated cells was observed, but did not reach statistically significant levels.

PMID- 9166933
TI  - Adhesion of tumour-infiltrating lymphocytes to endothelium: a phenotypic and
      functional analysis.
AB  - Efficacy of cancer immunotherapy with cultured tumour-infiltrating lymphocytes
      (TILs) depends upon infused TILs migrating into tumour-bearing tissue, in which
      they mediate an anti-tumour response. For TILs to enter a tumour, they must first
      bind to tumour endothelium, and this process depends on TILs expressing and
      regulating the function of relevant cell-surface receptors. We analysed the cell
      surface phenotype and endothelial binding of TILs cultured from human melanoma
      and compared them with peripheral blood T cells and with allostimulated T cells
      cultured under similar conditions. Compared with peripheral blood T cells, TILs
      expressed high levels of five integrins, two other adhesion molecules, including
      the skin homing molecule CLA, and several activation markers and showed markedly
      enhanced integrin-mediated adhesion to a dermal microvascular endothelial cell
      line in vitro. Compared with the allostimulated T cells, TILs expressed higher
      levels of the cutaneous lymphocyte antigen (CLA), the adhesion molecule CD31 and
      the activation markers CD30 and CD69, but lower levels of several other adhesion
      and activation molecules. These phenotypic and functional properties of TILs
      should have complex effects on their migration in vivo. Expression of CLA, the
      skin homing receptor, may increase migration to melanoma (a skin cancer), whereas
      integrin activation may cause non-specific binding of TILs to other endothelium.
      Manipulation of the culture conditions in which TILs are expanded might result in
      a phenotype that is more conducive to selective tumour homing in vivo.

PMID- 9166934
TI  - In vivo (31)P magnetic resonance spectroscopy and morphometric analysis of the
      perfused vascular architecture of human glioma xenografts in nude mice.
AB  - The relationship between the bioenergetic status of human glioma xenografts in
      nude mice and morphometric parameters of the perfused vascular architecture was
      studied using (31)P magnetic resonance spectroscopy (MRS), fluorescence
      microscopy and two-dimensional digital image analysis. Two tumour lines with a
      different vascular architecture were used for this study. Intervascular distances
      and non-perfused area fractions varied greatly between tumours of the same line
      and tumours of different lines. The inorganic phosphate-nucleoside triphosphate
      (P(i)/NTP) ratio increased rapidly as mean intervascular distances increased from
      100 microm to 300 microm. Two morphometric parameters - the percentage of
      intervascular distances larger than 200 microm (ivd200) and the non-perfused area
      fraction at a distance larger than 100 microm from a nearest perfused vessel
      (area100), - were deduced from these experiments and related to the P(i)/NTP
      ratio of the whole tumour. It is assumed that an aerobic to anaerobic transition
      influences the bioenergetic status, i.e. the P(i)/NTP ratio increased linearly
      with the percentage of ivd200 and the area100.

PMID- 9166935
TI  - Influence of single and multiple doses of amifostine on the efficacy and the
      pharmacokinetics of carboplatin in mice.
AB  - We have previously reported that amifostine potentiates the anti-tumour activity
      of carboplatin in mice. The present study was carried out in well-established
      human ovarian cancer xenografts OVCAR-3, A2780 and FMa grown subcutaneously in
      the nude mouse. It was found that a single dose of amifostine resulted in a
      higher increase in the anti-tumour activity of carboplatin than three doses of
      amifostine. A single dose of amifostine increased the AUC (area under the curve)
      values of total platinum in plasma ultrafiltrate (30.1 vs 18.2 microM x h), liver
      (307.7 vs 236.4 nmol g(-1) x h), kidney (500.8 vs 368.3 nmol g(-1) x h) and OVCAR
      3 tumour tissue (184.0 vs 146.8 nmol g(-1) x h). Despite this increase in total
      platinum, a decrease in platinum (Pt)-DNA adduct levels was observed in liver,
      kidney and bone marrow, which was significant in liver. In tumour tissue an
      insignificant increase in Pt-DNA adduct levels, specifically the Pt-GG adduct,
      was observed after treatment with a single dose of amifostine, which may explain
      the increase in anti-tumour activity. The increase in the AUC of total platinum
      was probably caused by a reduction in body temperature, which was most severe
      after three doses of amifostine. The extreme hypothermia may be the reason that
      three doses of amifostine resulted in less potentiation of the efficacy of
      carboplatin.

PMID- 9166936
TI  - Isolated hepatic perfusion in the pig with TNF-alpha with and without melphalan.
AB  - Isolated limb perfusion with tumour necrosis factor alpha (TNF-alpha) and
      melphalan is well tolerated and highly effective in irresectable sarcoma and
      melanoma. No data are available on isolated hepatic perfusion (IHP) with these
      drugs for irresectable hepatic malignancies. This study was undertaken to assess
      the feasibility of such an approach by analysing hepatic and systemic toxicity of
      IHP with TNF-alpha with and without melphalan in pigs. Ten healthy pigs underwent
      IHP. After vascular isolation of the liver, inflow catheters were placed in the
      hepatic artery and portal vein, and an outflow catheter was placed in the
      inferior vena cava (IVC). An extracorporeal veno-venous bypass was used to shunt
      blood from the lower body and intestines to the heart. The liver was perfused for
      60 min with (1) 50 microg kg(-1) TNF-alpha (n = 5), (2) 50 microg kg(-1) TNF
      alpha plus 1 mg kg(-1) melphalan (n = 3) or (3) no drugs (n = 2). The liver was
      washed with macrodex before restoring vascular continuity. All but one pigs
      tolerated the procedure well. Stable perfusion was achieved in all animals with
      median perfusate TNF-alpha levels of 5.1 +/- 0.78 x 10(6) pg ml(-1) (+/- s.e.m).
      Systemic leakage of TNF-alpha from the perfusate was consistently < 0.02%.
      Following IHP, a transient elevation of systemic TNF-alpha levels was observed in
      groups 1 and 2 with a median peak level of 23 +/- 3 x 10(3) pg ml(-1) at 10 min
      after washout, which normalized within 6 h. No significant systemic toxicity was
      observed. Mild transient hepatotoxicity was seen to a similar extent in all
      animals, including controls. IHP with TNF-alpha with(out) melphalan in pigs is
      technically feasible, results in minimal systemic drug exposure and causes minor
      transient disturbances of liver biochemistry and histology.

PMID- 9166937
TI  - Pretreatment with transforming growth factor beta-3 protects small intestinal
      stem cells against radiation damage in vivo.
AB  - The gastrointestinal tract, with its rapid cell replacement, is sensitive to
      cytotoxic damage and can be a site of dose-limiting toxicity in cancer therapy.
      Here, we have investigated the use of one growth modulator to manipulate the cell
      cycle status of gastrointestinal stem cells before cytotoxic exposure to minimize
      damage to this normal tissue. Transforming growth factor beta-3 (TGF-beta3), a
      known inhibitor of cell cycle progression through G1, was used to alter
      intestinal crypt stem cell sensitivity before 12-16 Gy of gamma irradiation,
      which was used as a model cytotoxic agent. Using a crypt microcolony assay as a
      measure of functional competence of gastrointestinal stem cells, it was shown
      that the administration of TGF-beta3 over a 24-h period before irradiation
      increased the number of surviving crypts by four- to six-fold. To test whether
      changes in crypt survival are reflected in the well-being of the animal, survival
      time analyses were performed. After 14.5 Gy of radiation, only 35% of the animals
      survived within a period of about 12 days, while prior treatment with TGF-beta3
      provided significant protection against this early gastrointestinal animal death,
      with 95% of the treated animals surviving for greater than 30 days.

PMID- 9166938
TI  - Clinical evaluation of urinary transforming growth factor-beta1 and serum alpha
      fetoprotein as tumour markers of hepatocellular carcinoma.
AB  - To evaluate the diagnostic application of urinary transforming growth factor
      beta1 (TGF-beta1) and serum alpha-fetoprotein (AFP) levels in hepatocellular
      carcinoma (HCC), TGF-beta1 and AFP were determined in 94 patients with cirrhotic
      HCC and in 94 sex- and age-matched patients with cirrhosis alone. TGF-beta1 and
      AFP levels in HCC were higher than in cirrhosis alone (P = 0.0001). There is an
      inverse correlation between TGF-beta1 and log AFP (r = -0.292, P = 0.004).
      Multivariate analysis indicated that TGF-beta1 and AFP were closely associated,
      in a dose-related fashion, with the development of HCC. Receiver-operating
      characteristic (ROC) curves were used to determine the optimal cut-off values of
      TGF-beta1 (50 microg g(-1) creatinine) and AFP (100 ng ml(-1)). Both TGF-beta1
      and AFP showed a high specificity (99%) and positive likelihood ratio. The
      sensitivity was 53.1% for TGF-beta1 and 55.3% for AFP. The determination of both
      markers in parallel significantly increased the diagnostic accuracy (90.1%) and
      sensitivity (84%), with a high specificity (98%) and positive likelihood ratio
      (40.0). In conclusion, TGF-beta1 and AFP are independent tumour markers of HCC
      and may be used as complementary tumour markers to discriminate HCC from
      cirrhosis.

PMID- 9166939
TI  - Expression of receptors for gut peptides in human pancreatic adenocarcinoma and
      tumour-free pancreas.
AB  - Gut hormones that modulate the growth of normal pancreas may also modulate the
      growth of cancers originating from pancreas. This study visualized and compared
      the receptors for cholecystokinin (CCK), bombesin (BBS), secretin and vasoactive
      intestinal peptide (VIP) in tumour-free tissue sections of human pancreas (n =
      10) and pancreatic ductal adenocarcinomas (n = 12) with storage phosphor
      autoradiography using radioligands. CCK-B receptors, present in control
      pancreata, were not detected in any of the pancreatic cancers. BBS receptors were
      visualized in control pancreata, but they were absent in 10 of 12 pancreatic
      cancers. In 5 of 12 pancreatic cancers, receptors for secretin were visualized,
      while binding for secretin was present in all tumour-free pancreata. Conversely,
      no specific binding of VIP was detected in control pancreata but was identified
      in 3 of 12 pancreatic cancer specimens. It is concluded that the expression of
      gut peptide receptors in pancreatic cancer differs from that in tumour-free
      pancreas. Receptors for these peptides are present in only a minority of
      pancreatic cancer specimens.

PMID- 9166940
TI  - Expression of the E-cadherin-catenin cell adhesion complex in primary squamous
      cell carcinomas of the head and neck and their nodal metastases.
AB  - Reductions in cell-cell adhesion and stromal and vascular invasion are essential
      steps in the progression from localized malignancy to metastatic disease. In this
      study, changes in the expression of the components of the E-cadherin-catenin cell
      adhesion complex have been investigated using immunohistochemical techniques in
      primary tumours and nodal metastases from 36 patients with squamous cell
      carcinoma of the head and neck. For 14 patients the corresponding primary and
      nodal metastases samples were available. None of the 51 samples showed normal E
      cadherin expression when compared with either the adjacent normal squamous
      epithelium or with normal colonic epithelium that was used as positive control
      material. In 88% of primary tumours fewer than 50% of cells exhibited normal
      membranous E-cadherin expression. Loss of membranous E-cadherin expression was
      more extensive in poorly differentiated carcinomas while, in individual
      carcinomas, membranous E-cadherin expression was stronger in those parts of the
      neoplasm that expressed the differentiation marker involucrin. Expression of beta
      catenin generally paralleled that of E-cadherin, but in 12 cases there was strong
      membranous beta-catenin expression in samples that exhibited predominantly
      cytoplasmic E-cadherin labelling. Expression of alpha-catenin was generally weak
      and did not correlate with the expression of either beta-catenin or E-cadherin.
      Marked intratumoral heterogeneity for protein expression was evident for all
      antibodies, and the abnormal expression of the catenins is a novel finding. E
      cadherin is expressed more intensely in cells with greater squamous
      differentiation, but there was no correlation between the decreased expression of
      any of the adhesion molecules of the E-cadherin complex tested and local
      recurrence, metastasis or survival. The loss of expression of components of the E
      cadherin complex is a common abnormality in squamous carcinomas and, while it may
      be permissive for metastasis, it does not appear to be the only determinant of
      this process.

PMID- 9166941
TI  - DC electrical field-induced c-fos expression and growth stimulation in
      multicellular prostate cancer spheroids.
AB  - The effects of electrical direct current (DC) field pulses on c-fos expression,
      growth kinetics and vitality patterns of multicellular tumour spheroids (MCSs)
      were studied. Monitoring the membrane potential of MCSs by di-8-ANNEPS staining
      and confocal microscopy during DC electrical field treatment revealed a
      hyperpolarization at the anode-facing side and a depolarization at the cathode
      facing side. When a single 500 V m(-1) electrical field pulse with a duration of
      60 s was applied to MCSs (150-350 microm in diameter) an enhancement of the
      growth kinetics within a period of 6 days post pulse was observed. Whereas the
      volume doubling time amounted to 4-5 days in control samples, it was reduced to 1
      2 days in electropulsed MCSs. At day 6 post pulse the diameter of the necrotic
      core was significantly smaller than the control. The critical diameter for the
      first appearance of central necrosis amounted to 350 +/- 50 microm in the control
      and 450 +/- 50 microm in the electropulsed MCSs. Coincidentally, the
      proliferating rim was increased to 107 +/- 11 microm in electropulsed MCSs as
      compared with 60 +/- 6 microm in the control. The growth stimulation may be
      mediated by the proto-oncogene c-fos as its expression increased by a factor of
      2.5 within 2 h post pulse. c-fos expression declined towards control values
      within 8 h post pulse.

PMID- 9166942
TI  - Granulocyte colony-stimulating factor receptor expression on human transitional
      cell carcinoma of the bladder.
AB  - Receptors for granulocyte colony-stimulating factor (G-CSFRs) have been confirmed
      on the cell surfaces of several non-haematopoietic cell types, including bladder
      cancer cells. This observation has naturally led to the hypothesis that the
      expression of G-CSFR on these cells may enhance their growth by G-CSF. In this
      study, the expression of G-CSFR was determined in both established human bladder
      cancer cell lines and primary bladder cancers. We studied five different human
      bladder cancer cell lines (KU-1, KU-7, T-24, NBT-2 and KK) and 26 newly diagnosed
      bladder tumours. G-CSFR mRNA expressions on cultured cell lines were determined
      using the reverse transcriptase polymerase chain reaction (RT-PCR) method.
      Furthermore, the G-CSFR binding experiments on the cultured cell lines were
      conducted using the Na(125)I-labelled G-CSF ligand-binding assay method.
      Moreover, the G-CSFR mRNA expressions on primary bladder tumour specimens were
      assessed using the in situ RT-PCR method. Three out of the five cultured cell
      lines (KU-1, NBT-2 and KK) exhibited G-CSFR mRNA signals when the RT-PCR method
      was used. The G-CSFR binding experiments showed an equilibrium dissociation
      constant (K[d]) of 490 pM for KU-1, 340 pM for NBT-2 and 103 pM for KK cells.
      With in situ RT-PCR, the tumour cells of 6 out of 26 primary bladder tumour
      specimens (23.1%) presented positive G-CSFR mRNA signals. Thus, in this study, G
      CSFR expression was frequently observed on bladder cancer cells. Therefore, the
      clinical use of G-CSF for patients with bladder cancer should be selected with
      great care.

PMID- 9166943
TI  - Liver and tumour tissue concentrations of TNF-alpha in cancer patients treated
      with TNF-alpha and melphalan by isolated liver perfusion.
AB  - In this study we determined the level of tumour necrosis factor alpha (TNF-alpha)
      in liver and tumour tissue samples obtained from patients with colorectal
      metastases confined to the liver, who were treated with isolated liver perfusion
      with TNF-alpha and melphalan. We adapted a standard enzyme-linked immunosorbent
      assay kit for the quantification of TNF-alpha in serum to measure the amount of
      this cytokine in solid tissue. For this purpose, we developed a buffer that lysed
      the tissues without affecting the TNF-alpha present. The minimum detection level
      was about 2 pg of TNF-alpha per mg tissue. Using this technique, we found a
      significant increase in the TNF-alpha level after perfusion in the liver tissue
      of all evaluable patients, which may explain the transient liver toxicity we
      observed in all patients. In tumour tissue, a significant TNF-alpha increase was
      observed in one out of five patients. The level of TNF-alpha in all liver tissue
      samples and some of the tumours after treatment by isolated liver perfusion was
      much higher than the peak serum concentrations obtained after systemic
      administration of the maximum tolerated dose of TNF-alpha. Furthermore, we
      demonstrated that the level of TNF-alpha in the liver tissue samples was about
      seven to eight times higher than in tumour tissue. We concluded that regional
      liver treatment resulted in a relatively high local level of TNF-alpha, but also
      that this cytokine did not preferentially accumulate in tumour tissue.

PMID- 9166944
TI  - Overexpression of p53 protein during pancreatitis.
AB  - Overexpression of p53 correlates with neoplasia in many cytological specimens. To
      test the specificity of overexpressed p53 as a tumour marker for the detection of
      pancreatic cancer, we analysed cytological specimens of pancreatic juice samples
      from patients with pancreatitis or pancreatic carcinoma (n = 42) for p53 protein
      overexpression. p53 protein overexpression was found in 59% of patients with
      pancreatitis and 67% of patients with pancreatic carcinoma. Thus, the assessment
      of p53 protein overexpression is not useful in the diagnosis of pancreatic
      cancer. Overexpressed p53 during pancreatitis appears to be wild-type p53.
      Overexpression of p53 may result from DNA damage occurring during chronic
      inflammation. It is well established that p53 can induce apoptosis upon DNA
      damage. Consequently, we found apoptotic cell death in five out of five tested
      cytological preparations from patients with pancreatitis as well as in one out of
      one pancreatic carcinoma specimen.

PMID- 9166945
TI  - Intraoperative identification of sentinel lymph node in patients with malignant
      melanoma.
AB  - We report our experience with the technique of lymphatic mapping using patent
      blue V dye in patients with limb malignant melanoma. The technique is based on
      the hypothesis that embolic metastases occur along lymphatic channels to a
      'sentinel' lymph node: the draining lymph node nearest the site of the primary
      malignant melanoma. Patent blue V dye (0.5-1.0 ml) is injected intradermally
      around the site of the melanoma. Immediately the groin or axilla is opened and
      the blue lymphatic channels followed to the sentinel node. The node is removed
      and examined by both haematoxylin and eosin (H&E) and immunohistochemical
      staining. We have carried out this technique in 35 patients, all of whom had
      'clinically assessed' stage I disease. In all 35 patients, sentinel nodes were
      identified, and nine were found to contain unsuspected micrometastases. Our
      initial evaluation of intraoperative lymphatic mapping is very promising. The
      technique is practicable and easy to master. If 25% of patients with cutaneous
      malignant melanoma who are clinically stage I have nodal disease, this has great
      importance not only for staging and treatment but also for all future therapeutic
      trials.

PMID- 9166946
TI  - Comparative analysis of expression of the proprotein convertases furin, PACE4,
      PC1 and PC2 in human lung tumours.
AB  - Proprotein convertases mediate the production of a variety of peptidic mitogens
      by limited proteolysis of their precursors. These proteases may also participate
      in the autocrine production of such mitogens by cancer cells and thus contribute
      to the unchecked proliferation of these cells. As a step towards defining this
      contribution, we have examined the levels of four convertase mRNAs in human lung
      neoplasms using semiquantitative Northern blot analysis. Furin mRNA was expressed
      in all the tumours; its level in squamous cell carcinomas and adenocarcinomas was
      on average about threefold higher than in small-cell lung carcinomas (SCLCs).
      PACE4 transcripts were detected in eight of 14 adenocarcinomas and in seven of 17
      squamous cell carcinomas; they were detectable in only two of seven SCLCs. PC1
      mRNA was undetected in squamous cell carcinomas and in all but two
      adenocarcinomas; it was present in four of six SCLCs. PC2 mRNA was found in two
      adenocarcinomas, in one squamous cell carcinoma and in five of seven SCLCs. This
      preliminary survey indicates that SCLCs often carry more mRNA for the endocrine
      convertases PC1 and PC2 and less mRNA for the more ubiquitous furin and PACE4,
      suggesting inverse roles of these convertases in the development of this
      neoplasm.

PMID- 9166947
TI  - Measurements of tissue polypeptide-specific antigen and prostate-specific antigen
      in prostate cancer patients under intermittent androgen suppression therapy.
AB  - The present study evaluated serial serum measurements of tissue polypeptide
      specific antigen (TPS) in comparison with prostate-specific antigen (PSA) for
      assessment of tumour progression in patients with advanced prostate cancer
      receiving intermittent androgen suppression therapy (IAS). Twenty-three men were
      recruited into an IAS trial consisting of an initial 8 months of androgen
      suppression, followed by cycles of treatment cessation and resumption of therapy
      upon increases of PSA > 20 ng ml(-1) to prolong the hormone responsiveness of the
      tumour cells. Periods of androgen suppression resulted in reversible reduction in
      serum testosterone (< 1.8 nmol I(-1)) and PSA (< 4 ng ml(-1)) and decreases in
      tumour volume (mean reduction for first cycle 24 +/- 10%), indicating partial
      growth arrest and apoptotic regression of the tumours. In contrast to PSA values,
      non-specifically elevated TPS values were found in 8 of 23 patients. In 15 of 23
      patients, TPS fell during periods of apoptotic tumour regression and increased
      simultaneously with testosterone and preceded the increases in PSA by 2 months
      during the period of treatment cessation. Although TPS represents a highly
      sensitive marker of tumour proliferation in this IAS clinical model of controlled
      tumour regression and regrowth, its low specificity compared with PSA limits its
      usefulness to monitoring of prostate cancer patients with proven absence of non
      specific elevations of this marker.

PMID- 9166948
TI  - Squamoid features and expression of involucrin in primary breast carcinoma
      associated with high histological grade, tumour cell necrosis and recurrence
      sites.
AB  - Although breast carcinomas are considered to originate from glandular epithelial
      cells, some exhibit 'squamoid features', comprising stratification with a
      gradient in the nuclear-cytoplasmic ratio within individual cancer cell nests on
      microscopy. In parallel with a histological review of squamoid features, we
      immunohistochemically investigated the expression of involucrin, a marker of
      terminal squamous differentiation, in 223 breast carcinomas with one to three
      regional nodal metastases but no distant metastases and analysed their
      association with other clinicopathological parameters to explore their clinical
      and biological implications. Squamoid features and involucrin expression,
      detected in 22% and 27% of cases respectively, correlated with each other and
      were associated with high-grade atypia, a solid-nest pattern, cancer cell
      necrosis on histology and negative oestrogen receptor status. The incidence of
      regional recurrences was higher in patients with involucrin expression, whereas
      bone metastases were less frequent in groups with squamoid features or with
      diffuse (> or = 10%) involucrin expression. Both squamoid features and involucrin
      expression, which were considered to be derived either from differentiation into
      keratinocytes or from some kind of cellular degeneration caused by high turnover
      rate, are suggested to influence the biological behaviour of breast cancer cells
      in vivo, and they may be effective in predicting the most likely recurrence
      sites.

PMID- 9166949
TI  - Prognostic impact of proliferation-associated factors MIB1 (Ki-67) and S-phase in
      node-negative breast cancer.
AB  - MIB1 proliferation rate (MIB1-PR) and total S-phase fraction (SPF) were
      retrospectively determined in formalin-fixed, paraffin-embedded sections of 90
      primary node-negative breast carcinomas. None of the patients had received
      adjuvant systemic therapy. Median follow-up in patients still alive at the time
      of analysis was 37.5 months (16-72 months). Immunostaining of Ki-67 antigen was
      performed using the monoclonal antibody MIB1 and the APAAP technique. An adjacent
      50-microm paraffin section was used for flow cytometric S-phase determination.
      Results were compared to established clinicopathological prognostic factors. MIB1
      PR was significantly correlated to grading (P = 0.018); SPF was significantly
      correlated with tumour size (P = 0.041) and inversely with steroid hormone
      receptor status (P = 0.03). A significant correlation between MIB1-PR and SPF was
      found in aneuploid (P = 0.025) but not in diploid tumours (P = 0.164). In
      univariate analysis, both MIB1-PR (optimized cut-off of 25%) and SPF (optimized
      cut-off of 8%) were significant prognostic factors for disease-free survival
      (DFS) (MIB1-PR, P = 0.0224; SPF, P = 0.0028). In multivariate analysis, however,
      only SPF remained significant; it was the strongest prognostic factor for DFS (P
      = 0.0073), stronger than MIB1-PR or established clinicopathological prognostic
      factors. We thus conclude that MIB1-PR and SPF provide additional prognostic
      information in node-negative breast cancer. However, in our study, flow
      cytometrically determined SPF had the greater prognostic impact.

PMID- 9166950
TI  - The association between population-based treatment guidelines and adjuvant
      therapy for node-negative breast cancer. British Columbia/Ontario Working Group.
AB  - This study evaluated the impact of province-wide treatment guidelines on
      consistency of adjuvant therapy for node-negative breast cancer. A retrospective
      population-based cohort study was conducted in the Canadian provinces of British
      Columbia, which has province-wide guidelines, and Ontario, which does not. All
      eligible 1991 incident cases of node-negative breast cancer in British Columbia
      (n = 942) and a similar number of randomly selected 1991 incident cases in
      Ontario (n = 938) were reviewed. Consistency of adjuvant therapy received was
      evaluated by stratifying cases into discrete diagnostic groups using several
      grouping systems, and by then comparing the distribution of treatments received
      within each diagnostic group in the two provinces. Recursive partitioning was
      also performed. We observed that patterns of pathology reporting were consistent
      with awareness of the factors used in the British Columbia guidelines to define
      indications for adjuvant therapy. Consistency of care was greater in British
      Columbia than in Ontario by all diagnostic grouping systems and by recursive
      partitioning (P < 0.001), and the observed patterns in British Columbia
      corresponded to the British Columbia guidelines. We conclude that population
      based treatment guidelines can play a role in promoting consistent patterns of
      adjuvant therapy for women with node-negative breast cancer.

PMID- 9166951
TI  - Prognostic value of histobiological factors (malignancy grading and AgNOR
      content) assessed at the invasive tumour front of oral squamous cell carcinomas.
AB  - Tumour cells at the invasive front of carcinomas have been found to differ
      substantially from the rest of tumour cells in a variety of human cancers. The
      present multivariate survival analysis of 94 oral squamous cell carcinomas
      (OSCCs) revealed that both the argyrophilic nucleolar organizer regions
      associated protein (AgNOR) content of invading tumour cells and a multiparametric
      histopathological tumour front grade were significantly and independently
      associated with tumour-related death, irrespective of conventional Broders' grade
      and clinical stage of the tumours. High tumour front scores and AgNOR content at
      the invasive OSCC front thus seem to reflect increased malignant potential.
      Proliferative activity, assessed by standardized AgNOR analysis, most probably
      represents one of the biological features underlying the usefulness of evaluating
      the invasive tumour front.

PMID- 9166953
TI  - Microbiology of Borrelia burgdorferi.
AB  - This article reviews the natural history, taxonomy, physical structure, growth
      requirements, and molecular structure of Borrelia burgdorferi sensu lato, the
      causative agent of Lyme disease. These spirochetal bacteria are maintained in
      nature through an infectious cycle between wild mammals and ticks. Borreliae are
      fastidious, slow-growing bacteria, found only in association with their arthropod
      or mammalian hosts in nature, and propagatable in the laboratory in a rich growth
      medium. The characteristic shape of borreliae is imposed by periplasmic flagella,
      located beneath the outer membrane and attached to the protoplasmic cylinder. The
      outer membrane of borreliae contains a number of abundant lipoproteins that are
      of serodiagnostic utility and currently under consideration as vaccine targets.
      The borrelial genome is unique in structure, organization, and copy number.
      Recent experiments demonstrate the feasibility of specific gene inactivation as a
      means with which to study the biology of borreliae and the pathogenesis of Lyme
      disease.

PMID- 9166952
TI  - Prognostic significance of ras/p21 alterations in human ovarian cancer.
AB  - Ras/p21 oncoprotein expression and K-ras mutations were analysed by Western blot
      and/or K-ras oligonucleotide hybridization in 78 primary ovarian cancers, 20
      omental metastases, two low malignant potential tumours (LMP), nine benign
      ovarian tumours and 10 normal ovaries. A cut-off value of an integral of
      absorbance (i.a.) of 2.20, obtained by receiver operating characteristic (ROC)
      curve, was shown to be the best cut-off for defining p21 positivity. p21 levels
      were higher in malignant tumours than in benign tumours (median 2.10 i.a. vs
      median 1.22 i.a.; P = 0.014) and in omental metastases than in primary ovarian
      carcinomas (median 2.54 i.a. vs median 2.1 i.a.; P = 0.0089). p21 overexpression
      did not correlate with any of the clinicopathological parameters examined. Follow
      up data were available for 63 patients. A significant relationship was shown
      between p21 positivity and a shorter overall survival (OS) (P < 0.03) and
      progression-free survival (PFS) (P < 0.03). In multivariate analysis only the
      presence of ascites, p21 levels and epidermal growth factor receptor status
      retained an independent prognostic role. K-ras gene mutations were frequently
      detected in benign and low malignant potential tumours (71.4%), which were mostly
      mucinous (P = 0.0152).

PMID- 9166954
TI  - Lyme borreliosis: laboratory considerations.
AB  - The laboratory is frequently the primary source for making the diagnosis of Lyme
      borreliosis when the symptoms are vague and the clinical hallmarks are missing.
      However, the temptation to interpret the laboratory results out of context from
      the clinical history and presentation should be avoided since the laboratory
      tests for evidence of B. burgdorferi infection can also be problematic. These
      problems have included sensitivity/specificity problems, lack of standardization
      of both methology and interpretation, and lack of routine direct evidence (ie
      culture) testing. These problems are discussed as well as possible solutions. It
      should be noted that meaningful results can usually be obtained from these tests
      if caution is used in their interpretation and the clinical symptomatology,
      history, and examination are integrated with the laboratory results.

PMID- 9166955
TI  - Neuroborreliosis: central nervous system involvement.
AB  - Despite rapid dissemination of Borrelia burgdorferi throughout the body following
      initial inoculation, the clinical manifestations of this illness tend to involve
      specific organ systems preferentially. The nervous system, in particular, is
      frequently affected; involvement usually follows one of several distinct
      patterns. Most commonly, patients develop a lymphocytic meningitis,
      radiculoneuritis or cranial neuropathy, occurring singly or in combination.
      Patients with radicular involvement often have a myelopathic component as well.
      At the other extreme, rare patients will develop focal inflammation of the
      central nervous system, an encephalomyelitis, that appears to involve white
      matter more often than grey. More commonly, patients may develop cognitive and
      memory impairment-a mild encephalopathy. In some patients this may represent a
      subtle form of encephalomyelitis, while in others it is probably a "toxic
      metabolic" effect of systemic infection. Disease variability among patients
      probably is the result of multiple factors, including bacterial strain
      differences in virulence and organotropism, inoculum size, host immunity, and
      simultaneous co-infection with other tick-borne organisms. Accurate diagnosis
      remains somewhat problematic. The cerebrospinal fluid is almost always abnormal
      in the presence of active CNS infection. Intrathecal production of specific
      antibody can be demonstrated in over 90% of patients with meningitis or frank
      inflammatory encephalomyelitis; in patients with a milder encephalopathy this is
      less consistently observed. In most instances, diagnosis relies on a combination
      of demonstration of a specific immune response, and clinical judgment. In
      patients in whom the diagnosis is secure, appropriate antimicrobial therapy is
      highly effective in the vast majority of cases, although if there has been
      significant structural damage to the CNS, some residua may remain.

PMID- 9166956
TI  - Peripheral nervous system Lyme borreliosis.
AB  - There are acute and chronic Lyme neuropathies. The seasonal acute syndromes of
      cranial neuritis or radiculoneuritis are generally quite distinctive, but may
      cause diagnostic difficulty when one syndrome occurs without the other, when
      erythema migrans is absent or missed, and when meningeal signs are minimal or
      absent. The chronic Lyme radiculoneuropathies are less severe, and less
      distinctive. Their recognition depends on eliciting a history of earlier
      classical manifestations of Lyme disease and by laboratory testing. In both acute
      and chronic Lyme radiculoneuropathy, electrophysiologic testing often proves the
      presence of a sensorimotor, axon loss polyradiculoneuropathy. Both acute and
      chronic Lyme radiculoneuropathy have similar pathologic features and can be
      classified as a nonvasculitic mononeuritis multiplex. The pathogenesis is
      uncertain; both direct infection as well as parainfectious mechanisms may play a
      role. The treatment with which we have the most experience is intravenous
      ceftriaxone 2 g/day for 2 to 4 weeks. Improvement occurs rapidly over days to
      weeks in early Lyme neuroborreliosis, but slowly over many months in chronic
      neuroborreliosis.

PMID- 9166957
TI  - Lyme encephalopathy: a neuropsychological perspective.
AB  - A mild chronic encephalopathy may be the most common neurologic symptom in
      patients with late stage Lyme disease. The symptoms tend to be diffuse and
      nonspecific, and patients typically report memory loss, sleep disturbance,
      fatigue, and depression. Among patients with these symptoms, it is generally felt
      that those with abnormal cerebral spinal fluid (CSF) have a neurological basis to
      their illness. A comparison of Lyme patients, with and without abnormal CSF,
      revealed that only the abnormal CSF group had lower memory test scores than
      normal controls. However, most patients in both Lyme groups complained of memory
      loss and also reported significantly more symptoms of depression and fatigue than
      controls. Thus, while depressive symptoms may not be a factor in objective memory
      performance, they may indeed play a role in perceived memory loss. A survey of
      the neuropsychological literature suggests that active neurologic involvement,
      the psychological consequences of chronic illness, and possibly residual
      neurologic deficits from past infection with Lyme disease all may affect the
      patient's perception of cognitive dysfunction.

PMID- 9166958
TI  - Lyme disease in children.
AB  - Neurologic manifestations of Lyme disease are common in children, among whom the
      incidence of Lyme disease is higher than among adults. Cranioneuropathies, in
      particular palsy of the facial nerve, occur in approximately 3-5% of children
      with Lyme disease, followed in frequency by meningitis (1% of symptomatic
      children). Children with only non-specific symptoms such as headache, arthralgia
      or fatigue commonly are misdiagnosed as having Lyme disease. Although such non
      specific symptoms often accompany more specific signs and symptoms (e.g.,
      erythema migrans, arthritis) in children with Lyme disease, very rarely are non
      specific symptoms the sole manifestation of Lyme disease. A number of carefully
      conducted follow-up studies have indicated that the prognosis is excellent for
      children with Lyme disease who have been treated with standard antimicrobial
      regimens.

PMID- 9166959
TI  - Treatment and prevention of Lyme disease, with emphasis on antimicrobial therapy
      for neuroborreliosis and vaccination.
AB  - Antibiotic therapy is recommended for all forms of neuroborreliosis. Although
      stage 2 neuroborreliosis will usually resolve without any treatment, antibiotic
      therapy has been associated with faster resolution of symptoms and may prevent
      additional non-neurologic disease manifestations. Ceftriaxone is the most
      convenient parenteral agent for stage 2 and 3 neuroborreliosis because of its
      once-daily dosage. Available data indicate that a 2-4-week treatment course is
      adequate for most patients. Patients with isolated seventh nerve palsy may be
      treated with an oral agent (for example, doxycycline). Recombinant outer surface
      protein A of Borrelia burgdorferi is a highly protective immunogen for prevention
      of Lyme disease in experimental animals. Humoral immunity is sufficient for
      protection. A recombinant OspA vaccine has been licensed for prevention of Lyme
      disease in dogs. Licensure of an OspA vaccine for humans will depend on a
      critical analysis of the results of recently completed efficacy studies.

PMID- 9166960
TI  - Lyme neuroborreliosis in the rhesus monkey.
AB  - Although there are several animal models of Lyme disease, only the rhesus monkey
      model exhibits all of the key manifestations of the disease. After infection with
      Borrelia burgdorferi, rhesus monkeys develop signs of early localized, early
      disseminated, and chronic Lyme disease. Specific features include erythema
      migrans, uveitis, myocarditis, arthritis, and disease of the peripheral and
      central nervous system. One of the unique features of the rhesus monkey model is
      the development of Lyme neuroborreliosis. Peripheral nervous system (PNS)
      involvement is usually in the form of a mononeuropathy multiplex with primarily
      axonal-loss features. Evidence of central nervous system (CNS) disease has
      included CSF pleocytosis, meningeal inflammation, spinal cord lesions, and
      polymerase chain reaction (PCR) data consistent with chronic CNS infection. The
      pathogenesis of Lyme neuroborreliosis is not well understood, but it is likely to
      involve complex interactions between B. burgdorferi and host immune mechanisms.

PMID- 9166961
TI  - Mechanisms of injury in Lyme neuroborreliosis.
AB  - Neurologic injury in infection with Borrelia burgdorferi can be due to the direct
      action of the spirochetes and spirochetal products on neural cells. There is in
      vitro evidence for the adherence of this organism to neurons, to glia, and to
      Schwann cells. Adhesion was found to be associated with galactocerebroside, a
      glycolipid component of myelin, and could act as a receptor for B. burgdorferi in
      oligodendroglia and in Schwann cells. Another pathway for neurologic injury could
      be through amplification of the inflammatory response by newly invading organisms
      (acute) and persisting (chronic) organisms. There is experimental evidence for
      production of IL-6, TNF-alpha, and nitric oxide by neural cells exposed to B.
      burgdorferi. Similar findings have been obtained from neuroborreliosis patients.
      Although less likely, there is the possibility that autoreactive mechanisms could
      have a role in the development of some manifestations of neuroborreliosis.

PMID- 9166962
TI  - Immunologic mechanisms in Lyme neuroborreliosis: the potential role of
      autoimmunity and molecular mimicry.
AB  - Most of the clinical manifestations of Lyme disease are due to the local presence
      of the causative agent, Borrelia burgdorferi, in the affected tissues. However,
      the precise means of tissue damage are not well understood and there is no proof
      that the organism, live or dead, is always present. An understanding of the
      complex interaction between the organism, the immune response elicited by the
      organism, and the host can explain manifestations of the disease and persistence
      of symptoms and signs after the antibiotic-induced death of the organism. It is
      possible that dead spirochetes, or fragments thereof may persist and act as a
      focus of ongoing inflammation. Different immunogenetic types may predispose to
      different immunologic responses, with distinct clinical outcomes. Vascular
      changes induced by the infection, either by local infection or the effects of
      cytokines on the vessel wall, may underlie tissue pathology. Finally, the immune
      response to B. burgdorferi may elicit the production of antibodies capable of
      recognizing and damaging or modifying normal host tissues. Only by establishing
      the mechanisms causing tissue damage in Lyme disease can rational therapeutic
      strategies be developed. Only by understanding these mechanisms can physicians
      and patients interpret clinical responses to therapy and accurately appreciate
      the clinical prognosis.

PMID- 9166963
TI  - Lyme disease: an historical perspective.

PMID- 9166964
TI  - Good laboratory practice: the medical aspects.

PMID- 9166965
TI  - Biological variation in protein C, protein S and antithrombin concentrations in
      plasma of healthy subjects.
AB  - The analytical, intra- and inter-individual components of biological variation
      were estimated for protein C, protein S and antithrombin over a period of 6 weeks
      in a cohort of 17 apparently healthy subjects. Expressed as percentage activity
      (protein C and antithrombin) as a percentage concentration in normal human plasma
      (protein S), the mean values for men and women show no significant differences (p
      > 0.05) for any of the analytes studied. Calculated analytical goals (CV, %) for
      precision required for optimal patient care are: protein C, 2.9; protein S, 2.9
      and antithrombin 2.7. A single numerical index, called "index of fiduciality",
      was also calculated to demonstrate that the analytical performance of our method
      was satisfactory. The generally applicable differences (% activity or %
      concentration) required for two results to be significantly different (p < or =
      0.05) were calculated as: protein C, 17; protein S, 16 and antithrombin, 16. The
      usefulness of critical differences as guidelines for the interpretation of
      changes in serial results was investigated using an "index of heterogeneity" of
      intra-individual variation. The marked degree of individuality demonstrated for
      all the quantities indicates that, if conventional population-based ranges are
      used uncritically, major changes in analyte concentration may not be correctly
      identified for some patients, because observed values continue to lie within the
      reference range. The utility of conventional population-based reference intervals
      was determined by calculating a single numerical index, called "index of
      individuality". For protein C, protein S and antithrombin we found that five of a
      patient's specimens are required to achieve a 95% chance that the mean is within
      +/- 5% of the true value.

PMID- 9166966
TI  - A further study of seminal plasma: lactate dehydrogenase and lactate
      dehydrogenase-X activities and diluted semen absorbance.
AB  - Activities of total lactate dehydrogenase, which plays an important role in
      providing energy for cell metabolism, lactate dehydrogenase-X, an isoenzyme of
      lactate dehydrogenase supposed to be specific for germinal epithelium activity,
      diluted semen absorbance and some other properties have been measured in 51
      seminal plasma samples. Aiming to study its clinical use as a marker of
      seminiferous epithelium activity, determination of isoenzyme-X and investigation
      of correlation between it and the spermiogram properties were carried out.
      Besides lactate dehydrogenase and lactate dehydrogenase-X activity, their ratio
      and diluted semen absorbance were correlated with the different properties of the
      spermiogram, the best correlation of the enzymes being obtained with the total
      sperm count and motile sperm count. Correlation of diluted semen absorbance with
      the total sperm count and motile sperm count was also noted, whereas it did not
      correlate with sperm concentration and motility rate. The data suggests the
      clinical utility of these properties as reliable markers for both germinal
      activity and spermatozoid quality when "total sperm count" and "mobile sperm
      count" are used to define sperm properties instead of just sperm concentration
      and motility rate.

PMID- 9166967
TI  - Age and sex related alterations in serum and platelet monoamine oxidase.
AB  - The process of aging presents itself with various alterations in physiological
      events. Although the turnover of catecholamines increases with aging, there is a
      lack of response to catecholamines in target tissues. One of the key enzymes in
      catecholamine metabolism is monoamine oxidase. It has been suggested that tissue
      and serum monoamine oxidase activities show pathological alterations in various
      diseases while physiological fluctuations can also be detected in normals. The
      aim of this study is to determine the sex and age related changes of platelet and
      serum monoamine oxidase in healthy volunteers. In this study, 75 healthy
      volunteers of different ages (21-80 a) and sexes (40 females, 35 males) were
      included. Serum and platelet monoamine oxidase determinations were performed
      spectrophotofluorometrically by Tufvesson's (Scand J Clin Lab Invest 1970; 26:151
      4) and Kraml's (Biochem Pharmacol 1965; 14:1684-6) modified methods,
      respectively. While there was no significant difference in serum monoamine
      oxidase activities related to age and sex, platelet monoamine oxidase manifested
      a significant increase in females compared to males (p < 0.05) and the mean
      values in both sexes showed an increase with age (p < 0.001). The results of this
      study imply that platelet monoamine oxidase shows an age related increase which
      is more prominent in females.

PMID- 9166968
TI  - The influence of orchidectomy on collagen glycosylation of trabecular bone in
      rat.
AB  - This study evaluates the effect of male rat castration on the degree of collagen
      glycosylation of bone. Twenty 100-day-old male Sprague-Dawley rats were subjected
      to either orchidectomy (n = 10) or sham operation (n = 10). After surgery animals
      were divided at random into 2 groups: the first group (5 sham operated and 5
      orchidectomized) was sacrificed under anesthetic at 130 days of age, while the
      second group (5 sham operated and 5 orchidectomized) was sacrificed at 250 days
      of age. Femurs and tibiae were separated into cortical and trabecular bone,
      demineralized, hydrolyzed and analyzed by HPLC for hydroxylysine glycosides and
      hydroxyproline content. Orchidectomy causes an increased collagen glycosylation
      only in trabecular bone, as already observed in ovariectomized rats. However, the
      effect was not seen in the group of 130 day old rats, i.e. 30 days after
      orchidectomy, but was evident in the 250 day old rats, i.e. at 150 days from
      castration. These data suggest that collagen glycosylation could also be
      controlled by testosterone.

PMID- 9166969
TI  - Increased serum concentration of IgA2 subclass and IgA2/IgA1 ratio: specific
      markers of chronic alcoholic abuse?
AB  - Enhanced serum IgA concentrations are common in alcoholic liver cirrhosis, but
      functional differences between IgA subclasses and their relation with interleukin
      6 (IL-6) have not been described. Distinct immunoregulatory mechanisms may exist
      that selectively affect one subclass. This possibility prompted us to investigate
      the distribution of IgA1 and IgA2 subclasses in the serum of 25 heavy alcohol
      drinkers (alcohol: 80 to 200 g per day) without clinical disorders, in comparison
      with 35 patients affected by alcoholic liver cirrhosis, 29 viral hepatitis
      patients and 33 social drinkers as a control group. Mean (+/- SD) IgA2
      concentration (0.56 +/- 0.31 g/l) was significantly increased (p < 0.01) in heavy
      alcohol drinkers, with an IgA2/IgA1 ratio of 0.33 +/- 0.12, while the mean total
      IgA concentration was similar to the control group. Mean IgA1 and IgA2
      concentrations were significantly increased (p < 0.001) in alcoholic liver
      cirrhosis patients (6.13 +/- 4.52 g/l and 1.83 +/- 1.93 g/l respectively, with an
      IgA2/IgA1 ratio of 0.32 +/- 0.19) and viral hepatitis patients (3.66 +/- 2.59 g/l
      and 0.69 +/- 0.67 g/l respectively, with an IgA2/IgA1 ratio of 0.21 +/- 0.14)
      High serum IL-6 concentrations (34 +/- 33 ng/l) were correlated with elevated
      IgA1 and IgA2 concentrations only in patients with alcoholic liver cirrhosis.
      IgA2 subclass and IgA2/IgA1 ratio could therefore be used as markers of chronic
      alcohol abuse directly related to the extent and duration of the alcohol abuse
      and the effectiveness of alcohol withdrawal.

PMID- 9166970
TI  - Age dependency of infradian rhythms in enzymuria of female volunteers.
AB  - The enzyme excretion of dipeptidylpeptidase IV (EC 3.4.14.5), gamma
      glutamyltransferase (EC 2.3.2.2), and alanine aminopeptidase (EC 3.4.11) was
      pursued in three different age groups of female volunteers over a period of 70
      days. The first group (1-3 years: n = 6) consisted of girls living in a
      children's home, the second (26-50 years, n = 7) of medical staff and the third
      (65-87 years, n = 7) of the inhabitants of an old-age home. Subsequent to basic
      statistics the excretion patterns were analyzed by spectral analysis with the
      maximum entropy method. The mean values of all enzymes displayed a distinct age
      dependency. The highest levels of enzyme excretion were found in the early
      childhood. In all groups infradian changes of enzyme excretion were detected. In
      excretion of gamma-glutamyltransferase, longer periods between 12 and 24 days
      predominated during the early childhood, whereas in the middle, and in particular
      in the higher age, shorter dominant periods occurred more frequently. The
      excretion of alanine aminopeptidase displayed a similar tendency. Circaseptan
      periods (7 +/- 1 days) were rarely observed among the dominant periods of the
      maximum entropy method spectra. A correlation analysis of the individual
      excretion patterns revealed that the excretion of all three bush-border enzymes
      is most tightly correlated in the early childhood (coefficients of correlation up
      to 0.9). In contrast, the correlation between enzymes and creatinine excretion
      was low in all age groups.

PMID- 9166971
TI  - Biclonal immunoglobulin M dysglobulinaemia: evolving aspects in a case of primary
      Sjogren's syndrome.
AB  - The observation of suggestive clinical symptoms in a patient suffering from a
      Gougerot-Sjogren syndrome led to a search for a cryoglobulin. Unusual physico
      chemical features of this cryoglobulin were discovered, using standard
      electrophoresis, immunoelectrophoresis, immunofixation and electroimmunotransfer.
      The main unusual finding was that the cryoprecipitate was made up of a biclonal
      IgM kappa associated to polyclonal IgG. Therefore, we suggest that this new form
      of cryoglobulin be classified as a subtype IIb, thus distinguishing two subtypes
      in the usual classification.

PMID- 9166972
TI  - Carboxypeptidase N and creatine kinase-MB isoforms in acute myocardial
      infarction.
AB  - The aims of our study were to evaluate the plasma carboxypeptidase N activity in
      normal subjects and in patients with acute myocardial infarction and to delineate
      its relationship with creatine kinase-MB isoforms in monitoring of acute
      myocardial infarction, carboxypeptidase N being the major determinant of creatine
      kinase isoform conversion in plasma. The study was carried out in 34 healthy
      subjects and 19 patients with acute myocardial infarction diagnosed according to
      the World Health Organization (WHO) criteria in which the blood samples were
      collected immediately upon admission to the coronary care unit (median time 3.5
      hours), every 4 to 6 hours for 24 hours, and every 12 hours until the third day
      post admission. Carboxypeptidase N activity, total creatine kinase, creatine
      kinase-MB mass concentration and creatine kinase-MB isoforms were determined in
      each sample from acute myocardial infarction patients, whereas only
      carboxypeptidase N and total creatine kinase activities were assayed in samples
      from healthy subjects. The results showed a high variability in carboxypeptidase
      N values among healthy subjects (median = 200 U/l; interquartile range = 190-247
      U/l) and in the first available samples from acute myocardial infarction patients
      (median = 213 U/l; interquartile range = 234 U/l) without significant differences
      between groups and without a correlation between carboxypeptidase N and creatine
      activities either in healthy subjects or in acute myocardial infarction patients;
      in the latter group, however, a significant correlation (p < 0.01) with creatine
      kinase-MB calculated on all samples, was observed. In acute myocardial infarction
      patients carboxypeptidase N showed time-related variations, reaching the highest
      levels about 48 h after onset of chest pain. A statistically significant
      difference in carboxypeptidase N values (p = 0.0001) was found before and after
      creatine kinase-MB peak values as well as before and after MB2/MB1 normalization.
      Worthy of note is the finding that in two acute myocardial infarction patients
      presenting MB2/MB1 ratios lower than the cutoff value (1.5) throughout the period
      of observation, the baseline values for carboxypeptidase N were higher than in
      other patients studied. Our results suggest that the increase of carboxypeptidase
      N activity after infarction could be induced by an increase in endogenous
      substrate concentrations, in particular creatine kinase-MB released from damaged
      myocardium. Furthermore, high baseline levels of carboxypeptidase N will reduce
      the diagnosis efficiency of creatine kinase-MB isoforms in the diagnosis of acute
      myocardial infarction.

PMID- 9166973
TI  - State-of-the-art of serum total calcium measurement as investigated by split
      sample measurement with an ion chromatography candidate reference method.
AB  - We evaluated bias and inaccuracy of four frequently used routine test systems for
      serum total calcium, using a candidate reference method based on ion
      chromatography. The mean biases and 95% confidence intervals that we observed
      were 0.0 +/- 0.59% for Johnson & Johnson arsenazo(III), 1.3 +/- 0.62% for Beckman
      arsenazo(III), -0.4 +/- 0.44% for Beckman applying ion selective electrode
      measurement after sample dilution, and -1.9% +/- 0.42% for Boehringer o
      cresolphthalein. The inaccuracy of all test systems was usually < 4.7%
      (calculated as deviation of singlicates from ion chromatography). Both bias and
      inaccuracy are discussed in the light of specifications set by expert groups or
      derived from the biological variation of serum total calcium. The study revealed
      that the intrinsic quality of commonly used test systems for serum total calcium
      satisfies even some of the more stringent criteria for method bias and
      inaccuracy.

PMID- 9166974
TI  - Cathepsin B-like activity as a serum tumour marker in ovarian carcinoma.
AB  - Serum cathepsin B-like activity was determined in 75 patients with ovarian
      carcinomas and in control groups. Ovarian cancers were of FIGO stages I-IV.
      Control groups consisted of 15 healthy women, 20 patients with myomas of the
      uterus, and 17 with benign ovarian cysts. Preoperative results showed elevated
      cathepsin B-like activity in 100% of the patients with ovarian cancers in
      relation to healthy subjects and patients with myomas, and in 78% in relation to
      benign ovarian cysts. Cathepsin B activity increased progressively with the FIGO
      stage of the disease, but the differences among particular stages were not
      statistically significant. In serous tumours cathepsin activity was significantly
      higher only in comparison to endometrioid ones (p < 0.001). Antipapain capacity
      of cystatins in the sera was also determined. No significant correlation between
      cathepsin B-like, and antipapain activity of cystatins was found. Serum cathepsin
      B-like activity may be helpful in the preoperative differential diagnosis between
      ovarian carcinomas and benign ovarian or uterine tumours.

PMID- 9166976
TI  - Precautions with the use of the maximal allowable error.

PMID- 9166975
TI  - The direct determination of urinary oxalate by non-suppressed ion chromatography.
AB  - In this paper we describe a simple ion chromatographic method for determination
      of oxalate in urine. Acidified urine was diluted 1:2 with 0.03 mol/l benzidine
      hydrochloride in 0.3 mol/l boric acid to precipitate sulphate. The supernatant
      was passed through a C18-cartridge and 100 microliters of eluant were injected
      into an ion chromatographic system. Oxalate was measured by nonsuppressed
      conductivity detection. The detection limit for urinary oxalate was 0.05 mmol/l.
      The recovery for spiked urine samples was 101.5% with a CV of 4.5%. The within-
      and between-assay coefficients of variation were less than 4.5% and 2.5%,
      respectively. We found the results obtained by this method to be statistically
      equivalent to an enzymatic assay and a different ion-chromatographic method.

PMID- 9166977
TI  - Accuracy of cholesterol measurements in Italian clinical laboratories. Joint
      project GISSI prevention--Italian Society of Clinical Biochemistry. SIBioC GISSI
      Prevenzione Group.
AB  - We report the results of an external quality assessment scheme for serum total
      cholesterol measurement involving about 100 Italian laboratories participating in
      an epidemiological study of post myocardial infarction. Two frozen human serum
      pools with Abell-Kendall assigned values are distributed quarterly at the
      laboratories (up to now seven events occurred); the obtained results are
      evaluated and discussed. In one exercise (# 5) duplicated measurements were
      repeated on three different days. Eighty-five to 98% of the laboratories obtained
      results within the total error limits (+/- 8.9%). But, while precision
      (calculated on the six replicates of exercise # 5) is good (90% of the
      laboratories obtained CV < 3%), inaccuracy problems are evident in every event.
      Indeed the mean bias from the reference method value ranged from 1.54 and 3.49%
      in the various events.

PMID- 9166978
TI  - International Union of Pure and Applied Chemistry (IUPAC). International
      Federation of Clinical Chemistry (IFCC). Committee on nomenclature, properties
      and units: Properties and units in the clinical laboratory sciences. II. Kinds-of
      property.

PMID- 9166979
TI  - International Federation of Clinical Chemistry (IFCC). Recommendation on mean
      molar activity coefficients and single ion activity coefficients of solutions for
      calibration of ion-selective electrodes for sodium, potassium and calcium
      determination.
AB  - In principle, flame photometry measures substance concentration, and ion
      selective electrodes (ISEs) measure ion activity. However, the situation
      regarding the comparison of results from the two techniques when applied to blood
      plasma is complex. The problem can be approached experimentally from the point of
      view of calibration of ion-selective electrodes with concentration calibrators,
      and similar procedures are adopted for commercial ISE-based clinical analysers.
      Nevertheless, there is interest in the evaluation of single ion activities in
      blood plasma and solutions simulating its ionic composition. Solutions are
      proposed for calibrating ion-selective electrodes for the determination of
      sodium, potassium and calcium. It is recommended that the values for single ion
      activities derived from the Pitzer treatment of mixed electrolyte solutions be
      adopted, because, although this has some empirical features, it has a sounder
      theoretical basis than the previously used Stokes-Robinson-Bates hydration
      approach.

PMID- 9166980
TI  - The decreasing incidence of left ventricular remodeling following myocardial
      infarction.

PMID- 9166981
TI  - Left ventricular remodeling: clinical significance and therapy.

PMID- 9166982
TI  - Remodeling after myocardial infarction: an opportunity for early intervention.

PMID- 9166983
TI  - Regional dysfunction and ventricular remodeling in the infarcted patient.

PMID- 9166984
TI  - Tissue repair and angiotensin II generated at sites of healing.

PMID- 9166985
TI  - Collagen and ventricular remodeling after acute myocardial infarction: concepts
      and hypotheses.

PMID- 9166986
TI  - Remodeling of the brain post myocardial infarction: focus on central ANF.

PMID- 9166987
TI  - Significance of the DNA synthesis in hypertrophic cardiomyopathies.
AB  - DNA content and proliferating cell nuclear antigen (PCNA) expression were
      investigated in normal hearts, in hypertrophic from hemodynamic overload hearts
      and in hypertrophic cardiomyopathy (HCM). The aim of this study was mainly to
      determine whether the hyperdiploid myocardial cells in all cases are in dynamic
      or static phase. The percentage of PCNA positive cells only in the HCM group was
      significantly higher (mean value = 25.4%) than the percentage of hyperdiploid
      cells (mean value = 9.3%). Therefore, the DNA replication occurs through a
      different process from that of normal cell cycle which lead to an increase in
      ploidy and eventually mitosis. These data should be interpreted not only as the
      result of a periodic amitotic DNA renewal and not even as the result of an
      increased apoptosis, but especially as a repair process of the DNA molecules
      affected by a various types of damages in HCMs.

PMID- 9166988
TI  - Effects of trimetazidine on the calcium transport and oxidative phosphorylation
      of isolated rat heart mitochondria.
AB  - Trimetazidine (TMZ) added in vitro to isolated cardiac mitochondria at
      concentrations 10-100 microM in the presence of 25-100 nM extramitochondrial Ca2+
      increased Ca2+ uptake and matrix Ca2+ concentration. This effect was less evident
      in the presence of physiologically Na+ and Mg2+ extramitochondrial concentrations
      since only 100 microM TMZ was able to increase mitochondrial Ca2+ entry in the
      presence of 100 nM Ca2+. The drug stimulated a Ca(2+)-cooperative effect on
      mitochondrial Ca2+ transport, but did not modify the rate of Ca2+ egress
      stimulated by 10 mM NaCl. An increase in mitochondrial Ca2+ level produced by TMZ
      enhanced oxoglutarate dehydrogenase activity and then ATP synthesis, particularly
      when 50 nM extramitochondrial Ca2+ was used. These data suggest that a possible
      cardiac mechanism of action of TMZ at mitochondrial level could support ATP
      synthesis by elevating the mitochondrial Ca2+ level.

PMID- 9166989
TI  - Glycosylation enhances oxygen radical-induced modifications and decreases
      acetylhydrolase activity of human low density lipoprotein.
AB  - BACKGROUND: Posttranslational nonenzymatic glycosylation of native low-density
      lipoprotein (n-LDL) occurs both in vitro and in vivo in diabetic patients.
      Glycosylated LDL (glc-LDL) behave similarly to oxidized LDL in some respects. In
      fact, unlike n-LDL, uptake the glc-LDL can occur in part by the "scavenger"
      receptor(s), as also demonstrated for oxidized LDL. The enzyme acetylhydrolase,
      carried by LDL, catabolizes platelet activating factor (PAF). This enzymatic
      activity is inhibited in oxidized LDL. However, it is unknown whether glc-LDL
      have reduced acetylhydrolase activity. OBJECTIVE: The first aim of the study was
      to investigate whether glc-LDL were more susceptible than n-LDL to oxidative
      modification, and which different oxygen radical species were involved in the
      phenomenon. Moreover, in order to investigate whether glycosylation may affect
      acetylhydrolase, we also measured this enzymatic activity in both n- and glc-LDL.
      METHODS: In vitro glc-LDL and n-LDL were exposed to the oxidants
      xanthine/xanthine oxidase (X/XO; 2 mM and 100 mU/ml, respectively), or CuSO4 (10
      microM) for 18 hs at 37 degrees C. Parallel experiments were done in the presence
      of the superoxide radical scavenger superoxide dismutase (SOD; 330 U/ml), the
      hydrogen peroxide scavenger catalase (1000 U/ml), or the hydroxyl radical
      scavenger dimethylthiourea (10 mM) or dimethylsulfoxide (1 mM). Standards of PAF
      and lyso-PAF were visualized with iodine vapors after separation by thin layer
      chromatography. The distribution of label was determined by an imaging scanner.
      Labeled products were then isolated from the chromatography plate, and the amount
      of 3H-lyso-PAF formed was determined by liquid scintillation counting. RESULTS:
      Glc-LDL were more susceptible than n-LDL to lipid peroxidation (n-LDL 22.9 +/-
      3.4 vs 34.8 +/- 4.2* nmoles/MDA/mg of protein in glc-LDL oxidized by X/XO and n
      LDL 28.9 +/- 4.2 vs 40.4 +/- 4.1* in glc-LDL oxidized by CuSO4, *p < 0.05 vs n
      LDL). SOD, but not other scavengers, prevented peroxidation, indicating an
      obligatory role for superoxide radicals. Oxidation of glc-LDL also induced a
      higher degree of apolipoprotein-B100 modifications than n-LDL, with increased
      electrophoresis mobility and decreased TNBS reactivity. These effects were
      similarly prevented by SOD. Finally, acetylhydrolase activity was significantly
      lower in glc-LDL than in n-LDL. CONCLUSION: Glycosylation increases LDL oxidation
      due to superoxide radicals, and also reduces acetylhydrolase activity. These
      phenomenona may contribute to enhance and/or accelerate the progression of
      atherosclerosis in diabetic patients.

PMID- 9166990
TI  - Premedication with the opioid analgesic butorphanol raises the threshold for
      ischemic preconditioning in dogs.
AB  - Elucidation of the subcellular mechanism of myocardial ischemic preconditioning
      should be facilitated by precise knowledge of the biology of the cardioprotective
      response. Any proposed molecular mechanism for preconditioning must be initiated
      during the required ischemic stress period. The studies reported in this paper
      were undertaken to determine whether the infarct-limiting effect of four 5-min
      episodes of ischemia interspersed by reperfusion can be achieved by a single 5
      min episode. Adult open-chest mongrel dogs, premedicated with the analgesic
      butorphanol, and anesthetized with sodium pentobarbital, underwent occlusion of
      the circumflex coronary artery for 60 min, followed by reperfusion of 3 h.
      Treated dogs were preconditioned with one, two or four cycles of 5-min occlusion
      followed by reperfusion. Additional dogs, not premedicated with butorphanol, were
      either untreated (not preconditioned) or preconditioned with one cycle of
      ischemia. Infarcts were identified using triphenyl-tetrazolium chloride (TTC)
      macrochemistry and infarct size (as % of area-at-risk, AAR) was measured and
      analyzed (using analysis of covariance [ANCOVA]) with respect to coronary
      collateral blood flow (measured using radioactive microspheres). Four 5-min
      cycles of preconditioning ischemia markedly limited infarct size. Two cycles were
      as effective as four. In contrast, infarct size was not different from control
      infarct size after a single episode of preconditioning ischemia. However, when
      pentobarbital anesthesia was used without premedication with butorphanol, a
      single 5-min ischemic stress did induce cardioprotection. Thus, the ischemic
      stress required for myocardial preconditioning in dogs is dependent on the
      anesthetic and premedication protocol employed. A single 5-min stimulus is
      effective in dogs anesthetized with pentobarbital. Premedication with the opioid
      analgesic, butorphanol, increases the threshold for induction of
      cardioprotection.

PMID- 9166991
TI  - Effect of aortic impedance on preload-afterload mismatch in canine hearts in
      situ.
AB  - The aim was to examine the influence of the independent increase of aortic wall
      characteristics from vascular resistance on global left ventricular (LV) function
      in intact hearts. In 11 anesthetized dogs, aortic stiffness was increased by a
      constriction of the thoracic aorta using a stiff tube, and then, in nine dogs,
      total systemic resistance (TSR) was increased by an infusion of angiotensin II.
      During the above procedures, aortic input impedance and LV dimension were
      measured. Aortic input impedance spectra revealed the steady increase in the
      moduli at high frequencies by aortic constriction, indicating the increase in
      aortic stiffness. At the stage of increased aortic characteristic impedance (Zc)
      (134% of control) without a change in TSR, both LV end-diastolic diameter (LVEDD,
      99%, p < 0.01 and stroke volume (SV, 95%, p < 0.01) decreased significantly
      without a change in LV end-systolic diameter (LVESD). During the increase in TSR
      produced by angiotensin II (128% of control) without a change in Zc, LVEDD tended
      to increase and LVESD significantly increased (103%, p < 0.01) associated with a
      decrease in SV (94%, p < 0.01). LV systolic mean wall stress was increased by
      angiotensin II (118%, p < 0.01), whereas it was unchanged by aortic constriction.
      In conclusion, the isolated increase in aortic stiffness without a change in TSR
      was associated with a reduction in LV preload and SV.

PMID- 9166993
TI  - A clinical study on physiological response in electroacupuncture analgesia and
      meperidine analgesia for colonoscopy.
AB  - Fifty-nine patients underwent consecutive colonoscopic examination with
      premedication of electroacupuncture analgesia (EA) were compared with
      conventional meperidine analgesia (MA) in pain relief and changes of
      neurotransmitters in serum. The results showed that analgesic efficacy of both
      groups were the same but with less side effects in the EA group (P < 0.01)
      especially in regard to dizziness. Serum concentration of beta-endorphin in both
      groups has a similar curve change at 4 different phases during colonoscopy. Serum
      concentration of epinephrine, norepinephrine, dopamine and cortisol showed no
      significant difference between these two groups. The analgesic effect of EA and
      MA during colonoscopic examination may be closely related to beta-endorphin
      production in serum.

PMID- 9166992
TI  - A review of problems in clinical acupuncture research.
AB  - Although laboratory studies indicate that acupuncture can have physiological
      effects, clinical studies of acupuncture are frequently inconclusive. Randomized
      controlled trials are the best way to test for the specific effectiveness of a
      therapy. Problems in clinical acupuncture research include the diversity of forms
      of therapy, individualised treatments, binding, choosing a credible control
      procedure, selecting suitable endpoints and traditional diagnosis. The enthusiasm
      of proponents of acupuncture may bias the research they are performing. None of
      these difficulties is insurmountable. Examples of rigorous trials are listed and
      some suggestions are offered on ways of improving research.

PMID- 9166994
TI  - Effects of moxibustion on blood pressure and renal function in spontaneously
      hypertensive rats.
AB  - The aim of this study was to investigate the effects of moxibustion at the
      meridian points BL-15 (Xin-shu) and BL-27 (Xiao-chang-shu) on renal function,
      systolic blood pressure, plasma levels of renin activity, aldosterone and atrial
      natriuretic peptide in spontaneously hypertensive rats. The results showed that
      urine volume increased significantly after moxibustion at the meridian points BL
      15, but decreased at BL-27. Urinary excretion of Na+ decreased after moxibustion
      at the meridian points BL-15 and BL-27. Systolic blood pressure decreased after
      moxibustion at the meridian point BL-15. No effect was observed at BL-27. Plasma
      levels of aldosterone and renin activity increased significantly, but the levels
      of atrial natriuretic peptide decreased significantly after moxibustion at BL-15.
      Plasma levels of aldosterone and atrial natriuretic peptide increased
      significantly after moxibustion at the meridian points BL-27. These results
      suggest that the meridian points BL-15 and BL-27 are related to the regulation of
      renal function and the secretion of hormone with body fluid metabolism.

PMID- 9166995
TI  - Polysaccharide peptide (PSP) restores immunosuppression induced by
      cyclophosphamide in rats.
AB  - Polysaccharide peptide (PSP) is a protein-bound polysaccharide extracted from an
      edible mushroom, Coriolus versicolor. Effects of PSP (2g/kg/day) on
      cyclophosphamide (CPA, 40 mg/kg/2 days)-induced immunosuppression were
      investigated by determining lymphocyte proliferation, Natural killer (NK) cell
      formation, IgG and IL-2 concentration, WBC count and the weight of organs after
      rats were treated with or without CPA in the presence or absence of PSP. The
      results demonstrated that PSP possessed immunopotentiating effect, being
      effective in restoring CPA-induced immunosuppression such as depressed lymphocyte
      proliferation, Natural Killer cell function, production on white blood cell and
      the growth of spleen and thymus in rats as well as in increasing both IgG and IL
      2 production on which CPA did not have significant effects under the conditions
      of our experiments. PSP can partly restore CPA-induced immunosuppression. Based
      on our findings and the data accumulated so far, it was suggested that PSP should
      be considered as an useful adjuvant especially combined with CPA or other
      chemotherapy in clinical treatment of cancer patients. The mechanism by which PSP
      restores the immunosuppression induced by CPA is unclear.

PMID- 9166996
TI  - Effects of baicalein on prostanoid generation from the lung and contractile
      responses of the trachea in guinea pig.
AB  - Effects of baicalein on release of slow reacting substance of anaphylaxis (SRS-A)
      or leukotriene (LT) from the sensitized guinea pig lung after antigen challenge
      and tonus of guinea pig tracheal muscles were studied. Baicalein inhibited
      release of SRS-A from sensitized guinea pig lung after antigen challenge. High
      performance liquid chromatography (HPLC) analysis revealed that released SRS-A
      consisted to LTC4 and D4. Baicalein also reduced release of LTC4 and D4 from the
      sensitized lung after antigen challenge. Baicalein relaxed the isolated guinea
      pig tracheal smooth muscle contracted by LTD4, carbachol or histamine. However,
      this compound produced a contraction when the tracheal muscle was contracted by
      prostaglandin F2 alpha(PGF2 alpha). This contraction by baicalein was abolished
      by pretreatment with indomethacin, a cyclooxygenase inhibitor. Baicalein elicited
      a relaxation in the normal non-sensitized preparation but a contraction in the
      tissue isolated from actively sensitized guinea pig in 4 among 7 cases. Baicalein
      also produced a contraction in the trachea pretreated with phorbol dibutyrate and
      contracted by carbachol, which was eliminated after treatment with indomethacin.
      The results suggest that baicalein exerts action via, at least, two different
      mechanisms, the inhibition of releasing SRS-A (LTs) and direct relaxing effects
      on the trachea. Besides, baicalein seems to produce contraction under certain
      conditions, which may involve stimulation of the cyclooxygenase pathway.

PMID- 9166997
TI  - Effects of Poncirus trifoliata on type I hypersensitivity reaction.
AB  - A study was carried out to examine the effect of an aqueous extract from immature
      fruit of Poncirus trifoliata L. (Rutaceae) (PTIFE) on the type I hypersensitivity
      reaction. Forty-eight hour PCA (passive cutaneous anaphylaxis) in rats was
      significantly inhibited by the oral administration of PTIFE (200 mg/kg). It also
      inhibited histamine release from rat peritoneal mast cells (RPMC) induced by
      mouse anti-dinitrophenyl (DNP)-IgE and dinitrophenyl-human serum albumin (DNP
      HSA). These results suggest that PTIFE has anti-allergic action against the type
      I hypersensitivity reaction.

PMID- 9166998
TI  - Preventive effect of oren-gedoku-to (huanglian-jie-du-tang) extract on
      progression of carbon tetrachloride-induced acute liver injury in rats.
AB  - The effect of oral administration of Oren-gedoku-to (Huanglian-Jie-Du-Tang)
      extract (TJ-15) on the progression of acute liver injury was examined in rats
      intoxicated with carbon tetrachloride (CCl4). When TJ-15 at a dose of 500 mg/kg
      body weight (b.w.) was administered to male Wistar rats aged seven weeks 6 hours
      after i.p. injection of CCl4 (1.0 ml/kg b.w.), an apparent liver injury occurred.
      Significant prevention against the progression of liver injury was found 24 hours
      after the injection judging from the activities of serum transaminases and other
      indices of liver cell damage. An increase in lipid peroxide level and decreases
      in reduced glutathione level and superoxide dismutase (SOD) activity occurred in
      the liver at 6 and 24 hours after CCl4 injection. Serum SOD activity increased 24
      hours after CCl4 injection. Post-oral TJ-15 administration significantly
      ameliorated all these changes found at 24 hours after CCl4 injection. An increase
      in liver triglyceride level and a decrease in serum triglyceride level also
      occurred 6 and 24 hours after CCl4 injection. Post-oral TJ-15 administration
      prevented the increase in liver triglyceride level at 24 hours after CCl4
      injection. Although the activity of liver tryptophan 2,3-dioxygenase (TDO), a
      marker of the inhibition of liver protein synthesis by CCl4, decreased 6 and 24
      hours after injection of the toxicant, post-oral TJ-15 administration had no
      effect on this decrease in TDO activity at 24 hours after the injection. These
      results indicate that oral TJ-15 administration can prevent the progression of
      acute liver injury in CCl4-injected rats, and suggest that this prevention could
      be due to the action of TJ-15 to scavenge free radicals formed in the liver and
      to inhibit triglyceride accumulation in the liver.

PMID- 9166999
TI  - Efficacy of toki-shigyakuka-gosyuyu-syokyo-to (danggui-sini-jia-wuzhuyu
      shengjiang-tang) on peripheral circulation in autonomic disorders.
AB  - To investigate the improvement in peripheral circulation in autonomic disorders,
      we monitored skin temperature in the tails of rats by thermography before and
      after the oral administration of boiled water extract of Toki-shigyakuka-gosyuyu
      syokyo-to (TSGS-to). Oral administration of this extract elevated the
      temperature, calculated as the calories of radiant heat in the rat tail 5-10 min
      after uptake. The temperature elevation remained stable for more than 20 min.
      Calories were significantly reduced 60 min after uptake and almost returned to
      initial values 90 min later. Some of the constituent herbs, especially Angelicae
      radix, Cinnamomi cortex, Evodiae fructus, and Zingiberis rhizoma, appeared to be
      active in relieving hypothermia.

PMID- 9167000
TI  - Effects of guan-mu-tong (Caulis aristolochiae manshuriensis) in combination with
      other natural products on normal and preneoplastic mammary gland growth in mice.
AB  - The effects of combined treatment with Guan-mu-tong (Gmt: Caulis aristolochiae
      manshuriensis) and other major components of Shi-Liu-Wei-Liu-Qi-Yin (SLWLQY), a
      Chinese herbal medicine prescribed for breast diseases, on normal and
      preneoplastic mammary gland growth were investigated. SHN virgin mice were
      divided into 6 groups at 3 months of age and treated with the samples in drinking
      water as shown in Table 2 for 8 weeks. Each sample was extracted repeatedly with
      hot water, dried in vacuo and dissolved with tap water at the concentration
      indicated in Table 2. Normal and preneoplastic mammary gland growth and
      thymidylate synthetase activity in the mammary gland were inhibited by Gmt alone;
      but its effect was affected slightly by the further addition of other products.
      However, the excretion of urinary components, which is abnormally low in SHN
      mice, was gradually enhanced by the addition of other products to Gmt and was
      highest by SLWLQY. The elongated estrous/metestrous stage of the estrous cycle
      induced by Gmt+Zq was returned to the control level by further addition of other
      products and by SLWLQY. The normal parameters in this strain during this age
      period such as body weight change, food and water intake and immune system were
      affected little by all treatments. All these findings strongly suggest that one
      of the principles of prescribing Chinese herbal medicines is to normalize the
      physical conditions, which, in turn, contributes to therapy and protection from
      diseases.

PMID- 9167001
TI  - Inhibition effect of shengma-gegen-tang on measles virus in Vero cells and human
      peripheral blood mononuclear cells.
AB  - Shengma-Gegen-Tang has long been used against measles virus in human peripheral
      blood mononuclear cells (PBMC) as well as in Vero cells. One hundred
      micrograms/ml Shengma-Gegen-Tang in PBMC displays significant anti-measles
      activity, whereas the same concentration in Vero cells does not. After eight days
      of infection, the release of virus is significantly suppressed by Shengma-Gegen
      Tang in the case of PBMC. In addition, Shengma-Gegen-Tang has a selective
      stimulation to the secretion of cytokine TNF-alpha in PBMC. Time kinetic analysis
      indicated that the stimulation of secretion was rapid and could be detected only
      2 hrs following the treatment of the PBMC. It rose to an optimal level in 8-12
      hrs. These findings suggest that the magnification of anti-measles virus activity
      of this agent is lymphocyte dependent and may well be mediated by TNF-alpha.

PMID- 9167003
TI  - Herbal teas and populace health care in tropical China.
AB  - Commercial Chinese herbal tea is the development of the populace in tropical and
      subtropical China consequential to their fight against infectious diseases and
      their struggle to explore local plants to relieve fever, to alleviate pain, to
      restore strength and to modulate immunity against viral epidemics. From these
      ethnomedical experiences, two types of herbal teas were commercialized, namely,
      liangcha and medicated teas. Liangcha refers to a ready-made decoction infused
      from wild plants served in simple stores in cities and towns. Medicated teas are
      parcelled material prepared from crude drugs with or without tea (Camellia
      sinensis [L.] O. Ktze,), sold in colorful boxes and bags to people for use at
      home. Investigations of liangcha were made in Hong Kong and Macao, and studies
      for medicated teas were done from samples obtained in Chinese stores at Boston. A
      total of 127 source species of these herbal teas were identified and arranged in
      two alphabetical lists by the botanical names, each followed by an English common
      name in parenthesis, part used, frequency in samples, and family. External
      recognizing characters of medicated teas, discussions of problems encountered in
      identifying source species, relevant toxicities, and potential new vegetal
      pharmaceutical resources are given.

PMID- 9167002
TI  - Effect of niuche-shen-qi-wan on painful muscle cramps in patients with liver
      cirrhosis: a preliminary report.
AB  - Twelve patients with liver cirrhosis complaining of painful muscle cramps were
      treated with Niuche-Shen-Qi-Wan (TJ-107). Three patients were at the
      decompensated state. Muscle cramps disappeared in 4 weeks on the average after
      oral administration of TJ-107 in all 12 patients. During the period of TJ-107
      administration, there was no significant improvement of hepatic function. One
      patient complained of mild epigastric discomfort after taking TJ-107, but there
      were no other adverse effects. Our results indicate that TJ-107 is useful for
      treatment of painful muscle cramps in cirrhotic patients.

PMID- 9167004
TI  - Laboratory tests for live attenuated poliovirus vaccines.
AB  - A new generation of tests to control live attenuated poliovirus vaccines are
      under development based on major advances in our understanding of the molecular
      basis of attenuation and reversion to virulence of polioviruses. These include an
      alternative in vivo neurovirulence test in transgenic mice that express the human
      poliovirus receptor and a new in vitro test, the MAPREC (mutant analysis by
      polymerose chain reaction and restriction enzyme cleavage assay, that assesses
      consistency of production at a molecular level. Excellent progress is being made
      with both methods but neither is sufficiently developed yet for regulatory use.
      Critical review of existing control tests shows that the WHO neurovirulence test
      is well standardized and contributes significantly to the assessment of each
      batch. On the other hand, the current rct40 test is neither standardized nor
      particularly informative, though improvements could be made in both areas. The
      continued relevance of other marker tests such as the d or antigenic marker is
      doubtful. Potency, identity and thermal stability tests are crucial for control
      of the final trivalent vaccine.

PMID- 9167005
TI  - Yellow fever vaccines.

PMID- 9167006
TI  - Japanese encephalitis and dengue vaccines.

PMID- 9167007
TI  - Laboratory tests for mumps vaccines.
AB  - The action of live attenuated vaccines against mumps is poorly understood
      although their clinical efficacy is beyond doubt. The attenuated character of the
      vaccine is assured by consistency of production related to clinical trials, and
      limited studies of vaccine seeds in primates. Potency is assessed by infectivity
      in vitro and is subject to poorly understood sources of variation. Molecular
      biological studies are at an early stage.

PMID- 9167008
TI  - Collaborative study on test systems to assess toxicity of whole cell pertussis
      vaccine.
AB  - A collaborative study has been carried out to establish the precision and
      accuracy of five test systems for the assessment of the toxicity of whole cell
      pertussis vaccine. To this end, six vaccines, including both "normal" and
      "abnormal" products with respect to arbitrary levels of Pertussis toxin and/or
      potency were tested. The study included in vivo test systems as the Mouse Weight
      Gain (MWG) test; the current WHO-recommended bioassay to evaluate overall
      pertussis toxicity and four specific test systems; the Leukocytosis Promotion
      (LP) test, the Histamine Sensitization (HS) test and in vitro the Chinese Hamster
      Ovary (CHO) clustering test to estimate pertussis toxin (PT) levels, and the
      Limulus Amoebocyte Lysate (LAL) test to evaluate endotoxin levels. In addition,
      participants were also asked to estimate potency by the Mouse Protection test
      according to Kendrick (MP). Fourteen laboratories in various countries
      participated in the study. In almost all participating laboratories, the MWG test
      was not very accurate in evaluating the overall toxicity of whole cell pertussis
      vaccines. In addition, statistical significant interlaboratory variation was
      frequently seen. The specific toxicity tests (LP, HS, CHO and LAL test) appeared
      to be more accurate, but large interlaboratory variation was seen, statistically
      significant at P < 0.05 for LP test, CHO test and LAL test. Significant variation
      in test results also occurred in the potency test. Furthermore, the
      discriminative power of the MP test between different levels of potency was low.
      It was concluded that, on the condition of optimization and stringent
      standardisation, HS and CHO test and in particular LP test might be more
      appropriate to assess PT activity than the MWG test provided that the tests are
      optimised and stringently standardized. An inhibition ELISA was used to estimate
      levels of PT. This test could be of value for prescreening purposes. The LAL test
      should be used to estimate endotoxin activity. The value of the MP test, as a
      model to assess potency, is disputed.

PMID- 9167009
TI  - A new WHO International Reference Reagent for use in potency assays of
      inactivated poliomyelitis vaccine.
AB  - Assays of the potency of inactivated poliovirus vaccine require the use of an
      appropriate reference reagent. Preparation 91/574 was shown by international
      collaborative study to be suitable for determination of antigenic content and
      immunogenicity of inactivated poliovirus vaccines by in vitro and in vivo assays,
      respectively. The reagent is a trivalent blend of formaldehyde-inactivated
      monovalent pools of poliovirus type 1 (Mahoney) poliovirus type 2 (MEF-1) and
      poliovirus type 3 (Saukett). Studies by antigen-capture ELISA showed that the
      component monovalent pools contained high titres of D antigen and trace amounts
      of C antigen. Sucrose gradient analysis showed that the D antigenicity was almost
      exclusively associated with 150S virus particles. Low levels of procapsids (75S
      particles with D antigenicity) were detected in the type 1 and 2 monovalent
      pools. The profile of intact virions and procapsids in 91/574 in sucrose
      gradients was very similar to PU78-02, a previously used inactivated trivalent
      poliovirus vaccine reference. The World Health Organization (WHO) Expert
      Committee on Biological Standardization at its 1994 meeting established
      preparation 91/574 as the 2nd WHO international Reference Reagent for
      poliomyelitis vaccine (inactivated). A potency of 430, 95, 285 D antigen units
      per ml was assigned to poliovirus type 1, 2 and 3, respectively. A separate
      aliquot of this preparation, established by the European Pharmacopeia Commission
      as a Biological Reference Preparation, has an identical assigned titre. The 2nd
      WHO International Reference Reagent 91/574 is intended for calibration of
      secondary reference reagents.

PMID- 9167010
TI  - Phenotypic features of BHK-21 cells used for production of foot-and-mouth disease
      vaccine.
AB  - BHK-21 c13 monolayer and suspension cells were investigated with regard to some
      phenotypic features which could bear on the quality of foot-and-mouth disease
      virus (FMDV) antigen produced in them. Despite good viability, suspension cells
      differed from monolayer cells in fundamental features of susceptibility to FMDV.
      Most important, FMD virus particles grown in suspension cells at high passage
      levels were shown to be largely degraded following inactivation with an aziridine
      compound. Suspension cells were characterised by a downregulation in the surface
      expression of both alpha 5 and alpha V integrin chains. According to the results
      of binding assays, both integrins could act as FMDV receptors on BHK-21 c13
      cells. Reduced surface expression of integrins was correlated with disappearance
      of actin stress fibres, which would play a role in regular encapsidation of viral
      RNA and hence in stability of virus particles. With regard to FMD vaccine
      production, practical suggestions are put forward to evaluate the quality of BHK
      21 c13 cells and FMDV Ag, which must prove stable during downstream processing.

PMID- 9167011
TI  - Authentication of animal cell cultures by direct visualization of repetitive DNA,
      aldolase gene PCR and isoenzyme analysis.

PMID- 9167012
TI  - Measurement of anticomplementary activity in therapeutic intravenous
      immunoglobulin preparations.
AB  - Anticomplementary activity (ACA) of aggregates in intravenous immunoglobulin
      preparations (IVIG) was investigated using the modified Kabat and Meyer classical
      complement consumption method recommended by the European Pharmacopoeia and a C1q
      coated microtitre enzyme-linked immunosorbent assay (ELISA). The physical
      characteristics of aggregates were found to affect complement binding. Aggregates
      formed by heating IVIG preparations at acid pH bound complement poorly, while
      aggregates formed by heating IVIG at neutral pH showed high ACA. This suggests
      that analysis of complement binding capacity provides a level of aggregate
      characterization of aggregates which is additional to quantitation by High
      performance liquid chromatography ((HPLC). The correlation (r = 0.98) between the
      two tests was good when aggregates formed at neutral pH were compared, but
      decreased (r = 0.57) when aggregates formed at acid pH were included. A
      comparison of the results showed that there were no significant differences in
      the classification of aggregates with acceptable/unacceptable (i.e. pass/fail
      outcome) values of ACA. Between assay variation (CV = 7.6%) was lower in the
      ELISA test compared with the complement consumption assay (where percentage
      binding varied from 78.9% to 100%). Both assays are justified for the evaluation
      of ACA in therapeutic IVIG. The ELISA had the advantage in being more precise,
      less dependent on reagent source and requiring less technical expertise.

PMID- 9167013
TI  - Evaluation of immune response and protection in animals given mink parvovirus
      vaccines.
AB  - In orthogonal and pair design tests, mink, guinea-pigs and rabbits were
      inoculated with inactivated mink enteritis virus (MEV) vaccine prepared with
      mineral oil or Al(OH)3 gel adjuvant. The animals were examined for serum
      haemagglutination-inhibition (HI) antibody during 6-55 days postvaccination
      (p.v.) and serum-neutralizing (SN) antibody for 11-31 days p.v. Differences
      between mineral oil and Al(OH)3 gel adjuvant vaccines in the induction of HI and
      SN antibodies during 6-55 days p.v. were not significant. There was significant
      positive rank correlation between HI antibody level and SN antibody index from 11
      to 31 days p.v. in serum of mink inoculated with the mineral oil or Al(OH)3 gel
      adjuvant vaccine (P < 0.05). The results of experimental challenge tests with
      vaccines in 29 mink showed a positive correlation between HI antibody titres, SNI
      and immune protective rates. Levels of HI antibodies in guinea-pigs, rabbits or
      mink during 11-40 days p.v. were reliable indices for monitoring the humoral
      immune responses and immune protective rates. The criteria for virus vaccine
      potency and vaccine immune efficiency is an HA titre of 64 for the cell-cultured
      MEV and an HI antibody titre of 32 for guinea-pigs, rabbits or mink during 11-40
      days p.v. The vaccine stimulates a protective response which lasts for a period
      of 12 months. The vaccine is stable for a period of 9 months at 4 degrees C.
      Economic, simple and scientific means have been developed to monitor the quality
      of MEV vaccines, of which more than 70,000 doses of the mineral oil vaccine and
      more than 18,000,000 doses of the Al(OH)3 gel vaccine have been used for the last
      5 years.

PMID- 9167014
TI  - Studies on isolation, serum-free cultivation and manufacture of mink enteritis
      virus optimized for vaccine preparation.
AB  - Optimum conditions have been determined for growth of mink enteritis virus (MEV)
      in the feline kidney cell (FKC) lines. The S18 and S36 strains of MEV grow to
      titres of 8192 to 32,786 haemagglutination (HA) units or 10(-9.7-10.3) TCID50 by
      alternate cultivation for 22 in FKC with very different susceptibility. Mink with
      typical clinical symptoms of mink viral enteritis (MVE) eliminated intestinal
      mucosal cylinders from which the L12 strain of MEV was isolated, which is capable
      of replication to 8192 HA units or 10(9.7) TCID50. The S18, L12 and S36 strains
      of MEV grow to high titres and the inactivated virus vaccine induced a good
      immune response in mink. The S18 and L12 strains of MEV are the best strains for
      vaccine preparation and the L12 strain is the most virulent for challenge tests.

PMID- 9167015
TI  - A rapid screen for lupus anticoagulant with good discrimination from oral
      anticoagulants, congenital factor deficiency and heparin, is provided by
      comparing a sensitive and an insensitive APTT reagent.
AB  - Lupus anticoagulants (LA) are associated with an increased risk of thrombosis and
      laboratory detection is of major importance. Various tests are available for LA
      screening and confirmation, but they differ in sensitivity and specificity,
      frequently lacking the ability to discriminate between the presence of LA,
      heparin and oral anticoagulants. We noticed that a patient with LA who had a
      prolonged activated partial thromboplastin time (APTT) by our routine method,
      gave a normal result with a different APTT reagent. This latter reagent, which
      contained soy bean phosphatides (SBP), was compared with a reagent containing
      rabbit brain phospholipids complexed with kaolin (RBK), for APTT measurement in a
      variety of patients. There was no significant difference in APTT ratio between
      the two reagents in plasma samples from healthy normal subjects. In LA samples,
      SBP gave consistently lower APTT ratios than RBK (mean +/- SEM, 1.04 +/- 0.05 and
      2.08 +/- 0.19 for SBP and RBK respectively; P < 0.001). In LA patients receiving
      oral anticoagulants for antithrombotic prophylaxis or treatment, the APTT ratio
      was again significantly shorter with SBP (1.60 +/- 0.17 and 3.40 +/- 0.67; P <
      0.05). In LA negative patients receiving oral anticoagulants, the relationship
      was reversed, and a higher APTT ratio was obtained with SBP than RBK (1.61 +/-
      0.13 and 1.31 +/- 0.12; P < 0.001). In addition, there were no significant
      differences in APTT ratios for the two reagents when samples from patients
      receiving heparin therapy, or patients with acquired factor VIII deficiency or
      inherited deficiency of factor VIII or IX were studied. The use of the SBP
      reagent alongside a LA sensitive APTT reagent allows a rapid screening for LA, as
      well as a confirmation of the phospholipid dependency of the inhibitor.

PMID- 9167016
TI  - Pharmacokinetic study of three synthetic AT-binding pentasaccharides in various
      animal species-extrapolation to humans.
AB  - The 'synthetic pentasaccharide', SR 90107A/Org 31540 (SP) representing the
      minimal AT-binding sequence of heparin is a catalyst of factor Xa inhibition.
      Affinity of SP, Sanorg 32701 (32701) and SR 80027 (80027), two close analogues of
      SP for rat, rabbit, baboon and human AT has been evaluated. The dissociation
      constants (Kd) for AT of the three species were in the range of 41-132, 1.4-6.2
      and 2.8-4.6 nM for SP, 80027 and 32701, respectively. Comparative
      pharmacokinetics (PK) of their anti-factor Xa activities were determined in rats,
      rabbits and baboons. An apparent correlation could be demonstrated between half
      lives of elimination and the corresponding Kd for AT in rats and rabbits whereas
      in baboons, such a correlation was not found. These results showed that despite
      Kd values ten times lower for 32701 than for SP, both compounds showed close PK
      parameters in baboons whereas the very low Kd value for 80027 was associated with
      an extended terminal half-life in this species. The predicted human PK parameters
      were determined using an allometric model: an empirical approach based on the
      integration of data obtained in various animal species which allows the
      extrapolation to humans. The values obtained for the terminal half-lives of SP,
      80027 and 32701 were 14.1, 88 and 6.5 h, respectively. For SP, calculation by
      allometry correlated well with the values observed in man. Since knowledge of
      duration of activity is pivotal for appropriate design of phase I clinical
      studies of anti-Xa oligosaccharides, allometry appears to be an interesting tool
      to predict the duration of action of such compounds in man.

PMID- 9167017
TI  - Prothrombin conversion under flow conditions by prothrombinase assembled on
      adherent platelets.
AB  - Prothrombin activation by prothrombinase was investigated on platelets adhered
      onto a fibrinogen-coated coverslip mounted in a flow chamber. Once bound to the
      fibrinogen, platelets gradually changed their morphology: they developed
      pseudopods, spread over the surface and finally transformed into balloon-shaped
      cells. This last morphologic change required the presence of calcium and was
      accompanied by the exposure of procoagulant phospholipid at the outer membrane as
      detected by the capability of the platelets to bind fluorescein-labelled annexin
      V. Prothrombinase complexes were allowed to assemble on these adhered platelets
      by perfusion with factor Xa and varying concentrations of factor Va and
      prothrombin. The steady-state rate of thrombin formation during continuous flow
      increased with the prothrombin concentration but not with the factor Va between
      0.05 and 0.5 nM. Once prothrombinase was assembled, factor Xa could be omitted
      from the perfusion mixture without affecting the steady state rate of thrombin
      production. Our study demonstrates the efficient ability of the procoagulant
      surface of adherent platelet to support the assembly of stable prothrombinase
      complexes. Thrombin production was limited by the rate of supply of prothrombin
      towards the catalytic surface.

PMID- 9167018
TI  - Long-term persistence of low-molecular-weight material with anti-factor Xa
      activity contributes to anticoagulant and antithrombotic effects after
      subcutaneous injection of CY 216 in the rabbit.
AB  - This study was done to document further the mechanism of the antithrombotic
      effect of CY 216 after subcutaneous injection in the rabbit. We first measured
      the circulating anti-factor Xa and anti-thrombin activities expressed in either
      International Unit or Standard Independent Unit and from these activities we
      calculated the above critical length material (ACLM) and below critical length
      material (BCLM) levels. The clearance of the BCLM was half that of the ACLM. Then
      we determined the inhibitory effect of CY 216 on thrombin generation (TG) in
      platelet-poor plasma (PPP) and in whole blood. TG was both inhibited and delayed
      in whole blood, while it was only inhibited in PPP. The IC50 on TG in PPP and in
      whole blood were 1.80 +/- 0.16 and 4.33 +/- 1.01 micrograms.ml-1 respectively.
      After the injection, the inhibition of TG was significant as long as BCLM was
      detectable. The duration of the antithrombotic effect was essentially correlated
      to the ACLM level in the Wessler-thromboplastin model and to the BCLM level in
      the Wessler-serum model. Taken together, these results demonstrate that both ACLM
      and BCLM components of CY 216 are involved in its anticoagulant effect ex vivo as
      well as in its antithrombotic activity in vivo, and that the relative
      contribution of BCLM increases with the time after administration.

PMID- 9167019
TI  - Effects of intermittent pneumatic compression on venous haemodynamics and
      fibrinolytic activity.
AB  - Pneumatic intermittent compression is an effective method to prevent
      postoperative venous thromboembolism. Its efficacy has been ascribed to both a
      haemodynamic action (increase of blood flow velocity) and a stimulation of
      endogenous fibrinolytic activity [via the production of tissue-type plasminogen
      activator (t-PA) by the vascular endothelium]. The relative contribution of these
      two effects is still debated. In a randomized, cross-over study in ten healthy
      volunteers, we compared the haemodynamic and fibrinolytic effects of two
      different pneumatic intermittent compression devices: a classical, low-pressure,
      whole-leg boots system, and a novel, high-pressure, plantar compression system.
      The study was performed at rest, to compare haemodynamics and fibrinolytic
      activity modifications, and under induced venous leg stasis, in order to compare
      the two compression systems in experimental conditions mimicking laparoscopic
      surgery. Our data show that (1) a pneumatic compression device that exerts its
      compression on the plantar venous plexus only induced an increase of venous blood
      peak velocity and flow in the common femoral vein that is very similar to that
      induced by the classical whole-leg boots compression system; (2) the venous
      stasis induced by an external pressure mimicking the conditions of laparoscopic
      surgery further increased the absolute velocity and flow increase, with the two
      intermittent compression systems tested; (3) no changes of t-PA or plasminogen
      activator-inhibitor 1 antigens were observed with either pneumatic compression
      device. In conclusion, the present study indicates that the antithrombotic effect
      of mechanical prophylaxis is probably mainly due to its ability to increase
      venous peak velocity and flow, especially under venous stasis conditions.

PMID- 9167020
TI  - Low prevalence of thrombophilic coagulation defects in patients with deep vein
      thrombosis of the upper limbs.
AB  - While many studies have demonstrated the pathogenetic role of inherited
      deficiency of natural clotting inhibitors in patients in the development of deep
      vein thrombosis of lower limbs, no data are available on the prevalence of these
      abnormalities in patients with upper vein thrombosis. In this study, antithrombin
      III, protein C, protein S, plasminogen, resistance to activated protein C and
      factor V Leiden mutation were assayed in 27 consecutive patients with thrombosis
      of upper extremities. Only two patients (7.4%) showed a congenital defect (one
      patient with deficiency of protein C, confirmed by family study, and one patient
      with factor V Leiden mutation). Anticardiolipin antibodies were also measured and
      four patients (14.8%) had increased levels, confirmed on a subsequent occasion 3
      months later. Eighteen out of 27 (67%) had a predisposing or triggering factor,
      thus emphasizing the role of physical stress in the development of upper vein
      thrombosis. At variance with what is observed in deep vein thrombosis of the
      lower limbs, inherited clotting abnormalities seem to be rarely responsible for
      upper vein thrombosis, whereas anticardiolipin antibodies and cancer are
      implicated in a significant proportion of cases.

PMID- 9167021
TI  - Asymptomatic coinheritance of heterozygous plasminogen deficiency and the factor
      VLeiden mutation.
AB  - Deficiency of plasminogen has been postulated by some authors as a possible
      thrombophilic abnormality, though this remains controversial. We have previously
      identified a cohort of individuals with plasminogen deficiency from a study to
      determine plasminogen levels within the general population. All were asymptomatic
      for thrombosis at initial identification. We followed this cohort over a 5-year
      period, with no venous thrombotic events recorded, although one patient did
      suffer a myocardial infarction. One family was identified with asymptomatic
      coinheritance of both plasminogen deficiency and the factor VLeiden mutation.
      There was no apparent venous thrombotic risk conferred upon any of our cohort of
      individuals by inheritance of plasminogen deficiency, and, in addition, the
      combination of the factor VLeiden mutation with plasminogen deficiency which was
      observed in three individuals did not result in thrombotic events. However, the
      cohort is small and we cannot entirely exclude plasminogen deficiency as a
      possible mild thrombophilic defect.

PMID- 9167022
TI  - Soluble P-selectin in hyperlipidaemia with and without symptomatic vascular
      disease: relationship with von Willebrand factor.
AB  - Soluble P-selectin (CD62P) may arise from platelets, the endothelium, or both,
      and raised levels are found in those with thrombotic disease and atherosclerosis.
      To determine whether these increased levels in atherosclerosis are related to
      hypercholesterolaemia, blood samples were obtained from 86 patients (43 with
      symptomatic vascular disease) attending a hypercholesterolaemia clinic, and 86
      age- and sex-matched controls. Parallel measurement of endothelial cell product
      von Willebrand factor helped define the origin of sP-selectin. Using ELISAs,
      soluble P-selectin was higher (median 290 ng/ml, range 80-735, P < 0.05) in
      patients with vascular disease than in both patients with uncomplicated
      hypercholesterolaemia (median 210 ng/ml, range 55-550), and controls (median 190
      ng/ml, range 48-500). Von Willebrand factor was raised in both patients with
      uncomplicated hypercholesterolaemia (115 +/- 26 IU/dl, P < 0.05) and patients
      with hypercholesterolaemia and vascular disease (129 +/- 32 IU/dl, P < 0.02)
      compared with controls (102 +/- 30 IU/dl). Levels of soluble P-selectin did not
      correlate with von Willebrand factor, total low-density-lipoprotein (LDL) or high
      density-lipoprotein (HDL) cholesterol or triglycerides levels, blood pressure or
      smoking, but von Willebrand factor correlated with LDL cholesterol (r = 0.42, P <
      0.05). We conclude that plasma lipoproteins are not a major influence on levels
      of soluble P-selectin.

PMID- 9167023
TI  - Further simplifications of the factor V: Q506 mutation detection test.

PMID- 9167025
TI  - Should we focus on the central nervous system in nonulcer (functional) dyspepsia?

PMID- 9167024
TI  - In vitro inhibition of heparin-induced platelet aggregation in plasma from
      patients with HIT by SR 121566, a newly developed Gp IIb/IIIa antagonist.

PMID- 9167026
TI  - Prospective evaluation of neutrophil autoantibodies in 500 consecutive patients
      with inflammatory bowel disease.
AB  - Previous studies have shown antineutrophil cytoplasmic autoantibodies (ANCA) in
      patients with inflammatory bowel disease (IBD). A particular subclass, the so
      called 'atypical' (perinuclear) p-ANCA type, occurs in the majority of patients
      with ulcerative colitis. The purpose of this prospective study was to assess, in
      a blinded fashion, this 'subclinical' serological marker in a consecutive series
      of IBD patients. Five hundred patients were evaluated, including 247 patients
      with ulcerative colitis and 253 with Crohn's disease involving the small and/or
      large intestine. Overall, 194 (38.8%) of all patients with IBD were positive,
      including 164 (66.3%) with ulcerative colitis and 30 (11.9%) with Crohn's
      disease. Except for coexistent sclerosing cholangitis, no other clinical or
      laboratory variable had an effect on the rate of ANCA detection. This is the
      largest single study of ANCA in patients with IBD and the only study to provide
      data solely from a single Canadian centre. Results emphasize the
      immunopathological differences between ulcerative colitis and Crohn's disease,
      and indicate that both disorders are heterogeneous inflammatory disease
      processes.

PMID- 9167027
TI  - Perforated duodenal ulcer in a pediatric patient with eosinophilic
      gastroenteritis.
AB  - An 11-year-old boy with eosinophilic gastroenteritis treated by an elimination
      diet alone presented with a perforated gastroduodenal ulcer subsequent to blunt
      trauma to the abdomen. Peripheral eosinophilia, chronic iron deficiency, chronic
      hypoalbuminemia and severe failure to thrive had been present since age 2 years.
      Immunological work-up revealed food allergies, documented by skin tests. A review
      of the literature since 1966 revealed only six other cases of perforation of the
      gastrointestinal tract, one of whom was also a child.

PMID- 9167028
TI  - Azathioprine-induced pericarditis in a patient with ulcerative colitis.
AB  - Inflammatory bowel disease is rarely associated with pericarditis but both
      sulfasalazine and the aminosalicylates have been known to cause this
      complication. To the author's knowledge this is the first reported case of acute
      pericarditis caused by azathioprine. It is believed that pericarditis is yet
      another potential manifestation of hypersensitivity to this drug.

PMID- 9167029
TI  - Endoscopists' opinions of indications for upper gastrointestinal endoscopy.
AB  - OBJECTIVE: To determine whether endoscopists and general internists agreed with
      the characterization of appropriateness for endoscopy of various clinical
      scenarios, as previously reported by the RAND Corporation. DESIGN: Mail survey.
      STUDY SAMPLE: All endoscopists in western Canada and a random sample of general
      internists who did not perform endoscopy. METHODS: Questionnaires were sent to
      179 endoscopists in western Canada who were asked to rate the 53 scenarios for
      endoscopy on a nine-point scale ranging from most appropriate to most
      inappropriate. A similar questionnaire was sent to 39 general internists
      practising in the province of Alberta. RESULTS: Response rate was 72% of
      endoscopists (n = 128) and 64% of general internists (n = 25). Among the
      endoscopists, there was agreement with the RAND classification for 32 scenarios.
      All 18 indications previously thought to be appropriate were considered to be
      appropriate. However, endoscopists agreed with only six of 16 equivocal and eight
      of 19 indications considered inappropriate. Discrepancies were reviewed by five
      experienced endoscopists and most appeared to be related to a concern regarding
      possible malignancy linked in part with the definition of failure to respond to
      medical therapy; and to a refusal to request a barium meal before endoscopy.
      Among general internists, there was agreement with RAND in 26 scenarios. When the
      appropriateness rankings of endoscopists and general internists were compared,
      there was agreement in 40 of 53 scenarios. Significant discrepancies in ratings
      were identified in scenarios in which barium studies were described as being
      normal, known or not done. CONCLUSIONS: The equivocal and inappropriate ratings
      developed by the RAND Corporation are not uniformly accepted by the endoscopy
      community or general internists. Use of the RAND indications for assessing
      quality assurance can be challenged.

PMID- 9167030
TI  - Late recurrent post-transplant primary biliary cirrhosis in British Columbia.
AB  - Late recurrent primary biliary cirrhosis (PBC) following orthotopic liver
      transplant remains a controversial topic. The first documented case of recurrence
      occurring in 16 patients transplanted for PBC and followed at the authors'
      institution for longer than one year is presented. A 54-year-old man transplanted
      for PBC developed a cholestatic pattern of enzyme elevation on post-transplant
      day (PTD) 1305. Repeat antimitochondrial antibody was strongly positive (1:300 to
      1:400). A liver biopsy revealed severe bile duct damage, lymphocytic cholangitis,
      focal periductal noncaseating granuloma and minimal endotheliitis. Recurrent PBC
      was diagnosed. At the time of orthotopic liver transplant this patient received
      induction immunosuppression with OKT3 crossed over to cyclosporine (CsA),
      azathioprine (AZA) and prednisone. AZA was discontinued early and maintenance CsA
      tapered to a target trough level of 150 to 200 ng/mL by PTD 365. Prednisone was
      withdrawn by PTD 664. CsA levels during PTDs 1225 to 1305 (before elevation of
      hepatobiliary enzymes) were below target at 114 to 166 ng/mL. Of the 16 patients,
      all but three were maintained on CsA, AZA and prednisone. One was on CsA (trough
      levels on target) and AZA; the other two, including the patient with recurrent
      PBC, were on CsA only. The trough CsA level of the patient without recurrent PBC
      has been within the target range. The authors speculate that the underlying
      defect in immunoregulation in PBC persists post-transplant and that in the
      patient without recurrent PBC this defect was unmasked by lowered maintenance
      immunosuppression--allowing recurrence of PBC in a previously stable liver
      allograft.

PMID- 9167031
TI  - Profile of a liver transplant follow-up clinic in a nontransplant Canadian urban
      centre.
AB  - Care of the growing number of liver transplant recipients will increasingly fall
      on the referring centres. Thus, there is a need to define more clearly the
      demographic, clinical and laboratory profiles of liver transplant recipients,
      particularly in the setting of a centre where a liver transplantation program
      does not exist. The present study documented these features in 37 patients
      attending an adult ambulatory care clinic in an urban, nonliver transplant
      centre. Mean +/- SD age of the study population was 44 +/- 11.9 years. Twenty-one
      patients (57%) were male. Annual enrolment in the clinic increased from three
      patients at the completion of the clinic's first year (1988) to 16 patients in
      the final year of the study (1993). Time between the transplantation procedure
      and the patient's return to the referring centre decreased from a mean of 12
      weeks in 1988 to four weeks in 1993. During those seven years no patient required
      an unscheduled return to the transplant centre for surgical complications or
      problems associated with immuno-suppressive therapy. In conclusion, these data
      provide a profile of liver transplant patients attending a nonliver transplant
      centre for follow-up and support the concept that nontransplant centres are
      capable of providing safe and, in terms of travel, less expensive care for liver
      transplant recipients.

PMID- 9167032
TI  - Adherence of Helicobacter pylori to the gastric mucosa.
AB  - Bacterial adhesion to the intestinal epithelium is a critical initial step in the
      pathogenesis of many enteric diseases. Helicobacter pylori is a duodenal pathogen
      that adheres to the gastric epithelium and causes gastritis and peptic
      ulceration. The mechanism by which H pylori causes disease has not been
      elucidated but adherence to the gastric mucosa is thought to be an important
      virulence determinant of the organism. What is known about adherence of H pylori
      to the gastric mucosa is summarized. Topics discussed are the mechanism of H
      pylori adherence; in vitro and in vivo models of H pylori infection; and
      adherence and potential adhesins and receptors for H pylori.

PMID- 9167033
TI  - Acute pancreatitis in childhood: research of pathogenesis and clinical
      implications.
AB  - Acute pancreatitis in children is more common than has previously been
      considered. A recent literature analysis has demonstrated significant resulting
      morbidity and mortality. Clinical awareness has improved dramatically, as
      demonstrated by the increase in the number of recent publications and etiological
      considerations. This review describes novel considerations in research related to
      the pathogenesis of acute pancreatitis and the arising clinical implications.
      This relationship is discussed regarding a better understanding of pathogenesis
      in pediatric disorders; increasing awareness; preventing damage by drugs and
      toxins; using novel diagnostic markers; and introducing new therapeutic tools.

PMID- 9167034
TI  - Budesonide in the management of patients with Crohn's disease.
AB  - Modern medical therapy is increasingly based on evidence. The evidence presented
      here is that budesonide (Entocort, Astra Pharma) 9 mg/day is superior to placebo
      and equivalent to systemically active glucocorticosteroids in achieving disease
      remission in patients with active Crohn's disease, and in prolonging the
      recurrence time of symptomatic disease. Budesonide causes less disturbance to
      adrenal function than prednisone or prednisolone and may cause fewer steroid
      associated symptoms. Thus, budesonide is the safer, more effective steroid of
      choice to treat patients with Crohn's disease.

PMID- 9167035
TI  - Maintenance therapy for inflammatory bowel disease: what really works.
AB  - The propensity of inflammatory bowel disease sufferers to experience recurrent
      episodes or disease flares is well documented. Until a cure can be found,
      strategies to lengthen the period of remission offer the greatest opportunity to
      reduce morbidity and enhance patient quality of life. Therapies that have been
      shown in randomized, controlled, double-blind clinical trials to either lengthen
      the time of remission or improve the odds of staying in remission during a set
      time interval are required.

PMID- 9167036
TI  - Immunohistochemical markers of tumor prognosis in breast cancer in Egypt.
AB  - Although the relationship among different biologic markers of breast cancer has
      been shown to be important in predicting cancer behavior, expression of these
      markers can be an attribute of the population under study. Breast cancer is the
      most common malignancy among Egyptian women. We have studied a number of
      prognostic tumor markers in infiltrating ductal carcinoma in a group of Egyptian
      women and have correlated our results with traditional histologic parameters of
      behavior such as tumor nuclear grade and lymph node status. Seventy-five cases of
      infiltrating ductal breast cancer were evaluated from pathology archives.
      Formalin-fixed paraffin-embedded sections were immunohistochemically stained for
      PCNA, p53, c-erB-2, metallothionein, cathepsin-D, and GST-pi using specific
      antibodies and a standard avidin-biotin method. Most high-grade tumors were
      associated with higher PCNA expression and p53 abnormality. There was a
      significant difference between node-negative and node-positive tumors with regard
      to their metallothionein content; other markers, however, did not differ
      significantly between node-negative and node-positive tumors. PCNA expression,
      metallothionein expression, and p53 mutation appear to be markers of aggressive
      tumor behavior in Egyptian women with breast cancer.

PMID- 9167038
TI  - The role of past mammography and future intentions in screening mammography
      usage.
AB  - Screening mammography is effective in the early detection of breast cancer among
      women aged 50 through 69, but under utilization by the target age group is
      common. The present study determined how past mammography behavior and intentions
      to have a mammogram were related to screening behaviors, attitudes, and beliefs.
      Participants were 1211 Alberta women aged 40 through 75 without breast cancer who
      were surveyed in a population-based random digit dial telephone interview. The
      response rate was 78%. Based on the stages of change and adoption models, women
      were grouped as Screeners (N = 363, 30%), who had had a "checkup" mammogram in
      the past 24 months and intended to have another in the next 24 months; Intenders
      (N = 355, 28%), who had not had a mammogram in the past 24 months but intended to
      have one in the next 24 months; and Nonparticipants (N = 513, 42%), who neither
      had had a mammogram in the past 24 months nor intended to have one in the next 24
      months. Compared with Screeners, both Intenders and Nonparticipants were more
      likely to live in the rural areas and to have lower educational levels.
      Nonparticipants were also older, less likely to be married, of lower income, and
      less likely to be employed outside of the home. Separate logistic regression
      analyses showed that both Intenders and Nonparticipants were significantly less
      able to encourage a friend to have a mammogram (OR = 2.7 and 4.4, respectively),
      more likely to believe that most women were not getting screening mammograms (OR
      = 1.7 and 2.9, respectively), and less likely to believe symptoms were not needed
      for mammograms (OR = 0.3 and 0.1, respectively). In addition, Nonparticipants
      were also significantly more likely to believe that getting a mammogram would not
      reassure others (OR = 4.0) and less able to talk to a doctor about getting a
      mammogram (OR = 5.2). Adoption of screening can be seen as a continuum in which
      Screeners had the most positive and Nonparticipants the most negative breast
      cancer screening attitudes, beliefs, and early detection behaviors. The
      importance of physician referral and utilization of other information
      dissemination channels was highlighted.

PMID- 9167037
TI  - Vimentin and alpha-fetoprotein expression in breast cancer smears: relationship
      with various prognostic factors.
AB  - Estrogen (ER) and progesterone (PR) receptor status, factors known to influence
      the prognosis and therapeutic possibilities in patients with breast cancer; alpha
      fetoprotein (AFP), which is an estrogen binder; and vimentin (V) were determined
      in cytological imprint smears of 75 mastectomy specimens. The results were
      classified according to tumor type and menopausal state and analyzed to determine
      possible relationships among these four markers under the different
      circumstances. There was a positive association of ER positivity with PR
      positivity, AFP positivity, and V negativity using chi 2 analysis. The lobular
      carcinomas studied were predominantly ER+, AFP+, V-, while in the ductal
      carcinomas V positivity was marginally predominant and also frequently associated
      with ER+ or PR+ status. The small number of medullary carcinomas made statistical
      analysis of this group difficult. It seemed probable that the marker status of
      the tumors was dependent more on the tumor type than on the menopausal state of
      the patients, thorough follow-up, especially of V+ medullary carcinomas, may
      provide insight into the value of vimentin as a primary rather than a secondary
      prognostic factor.

PMID- 9167039
TI  - Mass screening programs for breast cancer in France--average values of assessment
      criteria.
AB  - Breast cancer is the most common cancer in women worldwide. Many studies have
      been performed worldwide to assess the effectiveness of screening in terms of
      reduced mortality due to breast cancer. Since the end of 1989, 10 breast cancer
      mass screening programs using mammography have been carried out in France under
      the sponsorship of the National Fund for Health Prevention, Education, and
      Information (FNPEIS) from the National Health Insurance of Salaried Workers
      (CNAMTS). These 10 campaigns, which are on a district scale, are organized
      according to variable methods and are assessed using a common procedure. Four
      groups of criteria are measured in this procedure, which investigates the impact,
      quality, effectiveness, and costs of screening programs. The average and extreme
      values of each criterion as calculated from the campaigns are presented in this
      paper. In order to enlighten the judgment on the French results, a comparison
      with the international standards in force and with the results of foreign
      screening programs is proposed.

PMID- 9167041
TI  - DNA flow cytometry: a predictor of a high-risk group in cervical cancer.
AB  - We studied the relationship between the 5-year disease-free interval or the
      occurrence of distant metastases, and the flow cytometric nuclear DNA content in
      a group of 55 patients treated by radiation for squamous cell carcinoma of the
      uterine cervix, stages Ib-IIIb (FIGO). The diploid DNA content was associated
      with a better prognosis and a lower incidence of distant metastases, while
      aneuploid tumors tended to be prognostically unfavorable and had distant
      metastases more often. We consider the flow cytometric nuclear DNA content a
      prospective prognostic parameter in squamous cell carcinoma of the uterine cervix
      treated by radiotherapy.

PMID- 9167040
TI  - Factors influencing effect of mammography screening in a university workplace.
AB  - The purpose of this study was to examine the relationship between theoretically
      identified variables and participation in mammography screening in a university
      workplace. A sample of 1093 women 50 and over returned a questionnaire following
      the offer of a free workplace breast cancer screening. Anderson's Behavioral
      Model of Health Services Use identified factors predisposing and enabling women
      to have mammograms. Predisposing variables included attitudes and experience
      related to mammography. Enabling variables included income, willingness to pay
      for mammography, health insurance coverage, and regular source of health care.
      Comparisons were made among: (i) those who were screened in the workplace, (ii)
      those who were screened elsewhere, and (iii) those who were not screened.
      Differences in perceived barriers, perceived benefits, practice of breast self
      examination (BSE), and education surfaced. Results indicated, among other things,
      that women who were older, had no more than 12 years of education, had a family
      member with breast cancer, and were proficient with breast self-examination were
      more likely to have participated in the university work-site screening.

PMID- 9167042
TI  - Differentiation margins of ovarian tumor pathology: first incidences of
      epithelial ovarian tumors monitored by marker antibodies.
AB  - The first incidence of ovarian tumors in The Netherlands was analyzed during the
      PALGA data. The first incidences of benign epithelial ovarian tumors reach a
      plateau, at a level of 60 to 65 cases per 100,000 women beyond the age of 40
      years. The borderline malignant epithelial ovarian tumors account for 10 per
      100,000 women aged 30 to 85, while the ovarian carcinomas reach a plateau level
      of 25 to 35 per 100,000 women after the age of 50. Despite the long lag period
      (+/- 10 years) between benign and malignant ovarian tumors, the question of
      whether or not all epithelial ovarian cancers develop via an intermediate step of
      cystadenomas is still unanswered. Therefore, we examined whether the expression
      pattern of intermediate filaments and tumor antigens in normal, benign, and
      malignant ovarian tissues might contribute to this question. The following
      changes in expression pattern were observed: generally, all tumor cells retained
      the keratin profile of the corresponding original cell type. However, in a
      limited number of tumor samples ectopic keratin types, such as nos. 4, 10, 13,
      and 14, became expressed additionally. Most epithelial ovarian tumors and
      mesothelial cells coexpressed vimentin. The panepithelial marker BW495/36 clearly
      distinguished between negatively stained normal ovarian surface mesothelium and
      the positively stained (inclusion) cystic epithelium. TAG-72 as well as OV-632
      marked a subsequent tumor stage by discriminating between negative serous
      adenomas and positive serious carcinomas. TAG-72, however, stained both mucinous
      adenomas and carcinomas. The ovarian tumor markers (OC125, OV-TL 33, OV-TL16,
      MOv18), all showed an increasing expression level in the sequence order from
      normal cells to benign and malignant ovarian tumors. Both our epidemiological and
      our immunohistochemical data have shown that in the Dutch population there is a
      lag period of at least 10 years between the plateau levels of benign and
      malignant ovarian tumors. The early transformation of mesothelial cells to benign
      and/or malignant tumors is clearly marked by a switch on of the BW495/36 marker.
      Although no general transformation or progression marker from adenomas to
      carcinomas emerged from this study, TAG-72 might be considered a (progression)
      marker between the subgroup of benign and malignant serous ovarian tumors.

PMID- 9167043
TI  - Dietary influence on some proposed risk factors for colon cancer: fecal and
      urinary mutagenic activity and the activity of some intestinal bacterial enzymes.
AB  - This investigation studied the effects of a shift from a well-balanced mixed diet
      to a lacto-vegetarian diet on the mutagenic activity in urine and feces and on
      some cancer-associated bacterial enzymes in human feces (beta-glucuronidase, beta
      glucosidase, and sulphatase). Three months after the shift to the lacto
      vegetarian diet, there was a significant decrease in mutagenic activity in urine
      and feces, beta-glucuronidase, beta-glucosidase, and sulphatase per gram feces
      wet weight. In contrast, the fecal mutagenic activity and the enzyme activities
      remained unchanged if expressed per daily output. However, the urinary mutagenic
      activity expressed as total daily output decreased. Part of the explanation for
      the decreased fecal mutagenic activity and the decreased enzyme activities is
      obviously a dilution effect, because much of the increased fecal weight after the
      shift in diet was associated with a higher water content.

PMID- 9167044
TI  - The importance of self-observation of fecal blood in indicating a proper bowel
      examination.
AB  - This study presents a new model of screening for colorectal cancer. Persons aged
      50 or over in a city of 160,000 inhabitants were encouraged by a newspaper
      campaign to act on signs of fecal blood and to come forward for examination. A
      quantitative immunological human hemoglobin (Hb)-specific test method was
      employed, and, as a simple discriminatory help to minimize perianal
      contamination, a constringent local ointment was used. The group of fecal
      bleeders was examined by colonoscopy. Altogether, 1638 persons came forward to
      request screening. Of these, 168 were submitted for colonoscopy, and, among those
      18 colorectal cancers (11% of colonoscopies) were found. Of the cancers a
      significant part 28% were early cases (Dukes' A). In addition 28 adenomas were
      detected. The results show that there exists in the population a group of
      neglected fecal bleeders. Increasing the population's awareness of this symptom
      as a possible sign of colorectal cancer combined with prompt and proper medical
      investigations would lead to the detection of early cases of colorectal cancers.

PMID- 9167045
TI  - Clinical importance of interleukin-2 receptor alpha-chain expression in acute
      leukemia. The Japan Cooperative Group of Leukemia/Lymphoma.
AB  - To clarify the clinical importance of interleukin-2 (IL-2) receptor (IL-2R)
      expression in acute leukemia, we examined 517 adult patients with acute leukemia
      and CML blast crisis (CML-BC). IL-2R alpha was expressed in 42/311 AML, 5/11
      acute unclassified leukemia, 24/116 pre-B ALL, 2/32 T-ALL, and 27/47 CML-BC,
      while IL-2R beta was expressed only in 2 T-ALL. Expression of IL-2R alpha was
      closely associated with that of different lineage markers, CD11b, CD34, and Ph1+
      abnormality. IL-2R alpha(+) non-T leukemic cells did not respond to IL-2.
      Clinical outcome of IL-2R alpha (+) leukemia showed lower response to
      conventional chemotherapy and poorer prognosis than IL-2R alpha (-) cases. Serum
      IL-2R alpha level in IL-2R alpha (+) cases increased at the onset. Our findings
      indicate the diagnostic importance of IL-2R alpha expression in acute leukemia as
      a prognostic risk factor with a close relation to the particular cellular
      characteristics.

PMID- 9167046
TI  - Histological and immunohistochemical diversities, and proliferative activity and
      grading in osteosarcomas.
AB  - To examine the differentiation and proliferative activity of tumor cells, 30
      osteosarcomas, including osteoblastic, chondroblastic, fibroblastic, malignant
      fibrous histiocytoma-like, telangiectatic, giant cell-rich low-grade central, and
      epithelioid types, were studied immunohistochemically. A variable number of tumor
      cells in all cases showed osteocalcin immunoreactivity. In four preparations of
      the frozen sections, osteoblastic, fibroblastic, and chondroblastic tumor cells
      were positive for bone-type alkaline phosphatase antibody 2D3. S-100 protein
      immunoreactivity was found not only in seven tumors of the chondroblastic type,
      but also in four of nine osteoblastic tumors and each of the low-grade central,
      giant cell-rich, and epithelioid types. A histiocytic marker, CD68, was negative
      for tumor cells in all cases. Some cells of 17 tumors were positive for desmin
      and/or alpha-smooth muscle actin; this was regarded as an indication of
      myofibroblastic differentiation. Tumor cells of the epithelioid type and those of
      two osteoblastic tumors expressed cytokeratin (CAM5.2) and epithelial membrane
      antigen. Proliferating-cell nuclear antigen (PCNA) reactivity was found in the
      cell nuclei of 22 tumors, most of which were high grade. Many cells in six high
      grade tumors also showed the nuclear staining for p53 protein. Of these tumors,
      PCNA and p53 positivities tended to be more numerous in osteoblastic cells,
      atypical spindle-shaped, and bizarre giant cells than in well-developed chondroid
      cells. From these findings, osteosarcomas are concluded to be composed basically
      of osteoblastic cells, that are indispensable for diagnosis of osteosarcomas,
      with a variable number of chondroblastic, myofibroblastic, and, rarely,
      epithelioid cells, and this manifold cellular differentiation corresponds to the
      histological and clinical diversities. The osteoblastic, fibro- or
      myofibroblastic, and undifferentiated cells mainly participate in proliferation
      of osteosarcomas. The p53 gene alterations may play a part in the neoplastic
      transformation and proliferation of osteosarcomas.

PMID- 9167047
TI  - Changes in receptor function by oxidative stress in guinea pig tracheal smooth
      muscle.
AB  - We studied the effects of hydrogen peroxide, hypochlorous acid and ozone on
      muscarinic and beta-adrenergic receptor responses in guinea pig tracheal tissue.
      Pretreatment of the tracheal strips with hydrogen peroxide (up to 10 mM) did not
      affect the muscarinic or beta-adrenergic receptor responses after stimulation
      with methacholine or (-)-isoprenaline respectively. In contrast to hydrogen
      peroxide, hypochlorous acid (1 mM and 10 mM) decreased the maximal contraction
      and the pD2-value after stimulation with the muscarinic agonist methacholine.
      Comparable effects were observed after stimulation with the beta-adrenoceptor
      agonist (-)-isoprenaline but the beta-adrenoceptor response seemed to be more
      susceptible to hypochlorous acid treatment than the muscarinic response. In other
      words, hypochlorous acid changes the balance between muscarinic and beta
      adrenergic receptor responses of guinea pig tracheal strips in favour of the
      muscarinic receptor responses. In vivo exposure of the guinea pigs to 3 ppm ozone
      for two hours resulted in a hyperreactivity (increase in maximal contraction)
      after stimulation of the muscarinic receptor with methacholine. No effects were
      observed in the pD2-value. The beta-adrenergic receptor response was also
      affected after ozone exposure. No effects were seen in the maximal (-)
      isoprenaline induced relaxation but there was an increase (hypersensitivity) in
      the pD2-value. Our data suggest that oxidative stress modulates receptor
      responses. Moreover, the type of oxidant seems to differentially affect various
      receptor responses. This may be of importance to further understand the influence
      of an oxidative effect (either directly via ozone or through inflammation) in
      lung tissue.

PMID- 9167049
TI  - Respiratory tract lining fluid antioxidants: the first line of defence against
      gaseous pollutants.
AB  - All tissues are vulnerable to oxidant damage, but by virtue of its location,
      anatomy and function, the epithelial surface of the lung is one of the most
      vulnerable targets in the body. Recent studies have shown that epithelial lining
      fluid (ELF), a thin layer of fluid which covers the epithelial surface of the
      respiratory tract, contains an interesting complement of antioxidants, some of
      which, like glutathione, are present in concentrations much higher than those
      found in plasma. It is likely that ELF forms the first line of defence against
      inhaled toxins such as ozone and nitrogen dioxide. By employing an ex vivo
      exposure system we have demonstrated that when lung lining fluid is in contact
      with environmentally relevant concentrations of ozone or nitrogen dioxide, there
      is differential consumption of the water-soluble antioxidants in the order, uric
      acid > ascorbic acid >> glutathione. Given that the majority of ozone and
      nitrogen dioxide reacts within the ELF compartment, the antioxidant composition
      of this fluid is critically important in determining an individual's sensitivity
      to gaseous pollutants.

PMID- 9167048
TI  - The use of isolated lung cells in in vitro pulmonary toxicology: studies of DNA
      damage, apoptosis and alteration of gene expression.
AB  - Isolated lung cells constitute a valuable system for studying mechanisms involved
      in chemically induced toxicity in the lung. Different lung cells isolated from
      various species may be studied. Bronchiolar Clara and alveolar type 2 cells
      produce important lung-specific proteins, hold a major role in the metabolism of
      xenobiotics and serve as progenitor cells for other lung cell types. They are
      possible target cells in lung carcinogenesis. Alveolar macrophages play an
      important role in lung defence and in inflammatory responses. In the present
      study we have characterised chemically induced DNA damage, apoptosis, changes in
      cell cycle progression, transformation and alterations in gene expression in
      these specific lung cells isolated from rat, rabbit and human. Major differences
      between the cell types and the various species in the induction of DNA damage by
      chemicals were found, as measured by the 32P-postlabelling and alkaline filter
      elution techniques. Benzo(a)pyrene and hydrogen fluoride were found to induce
      apoptosis in the isolated cells as measured by microscopical analysis and flow
      cytometry. The function of various important tissue- or cell type specific
      proteins (CYP 2B1, Clara cell protein) and/or cellular signal transduction
      pathways constitute important targets that may be affected by exposure to toxic
      compounds. Using immunological and molecular techniques the differential
      expression of specific proteins/RNAs and their activity can be studied. Among
      other proteins, c/ebp is involved in the regulation of transcription at the end
      of signal pathways. The protein is differentially expressed in rat lung cells and
      thus could be suitable for studying differential toxic effects in various lung
      cells. In humans, bronchoalveolar lavage (BAL) fluid from human volunteers can be
      readily obtained and examined after exposure to different chemical compounds. An
      increase in the percentage of CD3-positive cells (T-lymphocytes) was found after
      exposure to hydrogen fluoride. The number of certain cell types and cytokines may
      be used to estimate the degree of inflammatory reaction. In conclusion, the use
      of in vitro data including the use of specific, primary human lung cell types may
      contribute considerably to the quality of risk assessment, together with in vivo
      data from animals and man.

PMID- 9167050
TI  - Mechanisms of action of some air pollutants on the airways.
AB  - Common air pollutants (O3, SO2) exert their deleterious effects in several ways,
      mostly on the respiratory functions. Ozone causes formation of peroxides and
      aldehydes with subsequent release of inflammatory lipids and cytokines. Changes
      in the activity of neutral endopeptidase and release of neuropeptides may occur.
      As a result, bronchial hyperreactivity can be detected. In the mechanisms of the
      disturbances due to sulfur dioxide, cholinergic mechanisms and release of
      neuropeptides may be involved.

PMID- 9167051
TI  - Air pollution and childrens' respiratory morbidity in the Tata area, Hungary.
AB  - Air pollution represents one of the most important environmental health hazards
      in Hungary. Irritant gases, like SO2 and NO2 levels exceed national and
      international standards in many settlements. Tata, a small town, situated in a
      basin, is one of the most polluted areas in Hungary. Longitudinal and cross
      sectional studies have been conducted in children in the winter period of
      1993/1994, with respect to SO2 and NO2 concentration. Average SO2 levels exceeded
      the national standard levels and daily peaks as high as 450 micrograms/m were
      recorded. Excessive NO2 levels were also found but they were not as high as those
      of SO2. Acute respiratory morbidity, based on a uniform protocol was recorded
      daily and evaluated on a daily and weekly basis. A statistically significant
      correlation with SO2 levels was observed in relation to the frequency of acute
      daily respiratory morbidity. Other health parameters, like pulmonary function,
      haematology and sensory performance were also tested. Although no statistically
      significant correlations were observed, the tendency in all parameters
      demonstrated impairment, in relation with ambient air pollution. Smoking history
      of the family did not alter significantly the pulmonary functions of other
      parameters.

PMID- 9167052
TI  - Crotonaldehyde: a carcinogenic and mutagenic air, water and food pollutant.
AB  - Crotonaldehyde is mutagenic and carcinogenic and it is ubiquitous in our
      environment. The data base does, however, not allow an assessment of the
      carcinogenic risk. We have developed a sensitive 32P-postlabelling technique
      which allows the detection of specific DNA-adducts in animal tissues as markers
      for initiation of cancer cells. Adducts were found in several organs of F 344
      rats after gavage and persisted to a certain extent. The determination of adduct
      levels in animal tissues after different exposure or even in human tissues can
      therefore be considered as an effect monitoring and would certainly improve the
      risk assessment.

PMID- 9167053
TI  - Clinical studies of effects of nitrogen oxides in healthy and asthmatic subjects.
AB  - Traffic and cooking and heating using unventilated gas appliances are the major
      sources for environmental exposures to nitrogen oxides. The nitrogen oxides of
      importance for health effects are nitrogen dioxide (NO2), and maybe the two
      derivatives nitric and nitrous acid (HNO3 and HNO2). Due to this, human exposure
      studies on NO2 have been performed intensively during the last decades. Nitric
      oxide (NO) is quantitatively the major pollutant, but is not very toxic and may
      even be used in treatment of certain conditions of respiratory insufficience.
      Major lung function effects shown in humans are a decrease in the forced
      expiratory volume in the first second (FEV1), increased specific airway
      resistance (SRaw), and increased responsiveness in bronchial provocation tests.
      Studies have been performed primarily on healthy and asthmatic subjects, but only
      asthmatic subjects show these reactions at levels relevant to exposures found in
      indoor and outdoor environments. Other effects found in animal studies and
      epidemiological studies like decreased mucociliary function, increased
      susceptibility to infections have not been proven in humans and are therefore
      still on debate. Human studies have furthermore shown that antioxidants like
      vitamin C and E may prevent effects of NO2, which is explained by that the
      mechanism of NO2-action is the oxidation of airway phospholipids. A large
      inconsistency in the results of the studies makes it very difficult to conclude
      about dose-response relationships and about no observed effect levels (NOEL).
      Single study observations and results of meta-analyses have indicated a biphasic
      dose-response relationship. However, such a relationship is hard to explain and
      need to be investigated further. Several other explanations, e.g. the limited
      statistical power of the studies, may exist and will be discussed.

PMID- 9167054
TI  - Impact of environmental pollution on chromosomes and DNA of inhabitants of Upper
      Silesia.
AB  - Highly industrialized and densely inhabited region of Upper Silesia, Poland,
      presents an area of ecological disaster. Air quality is bad, and does not meet
      any quality standards. In peripheral blood white cells, the level of chromosomal
      aberrations, sister chromatid exchanges and DNA-adducts in adult, male
      individuals exposed to environmental pollution exceed values found for males in
      non-industrialized region.

PMID- 9167055
TI  - Cellular effects of particles--impact of dissolution on toxicity of man-made
      mineral fibers.
AB  - The use of man-made vitreous fibers (MMVF) has grown rapidly because exposure to
      natural fibers, mainly asbestos, has proved harmful to humans. Biological
      activity of MMVF made of glass, rock, slag, or other minerals does not depend
      only on their respirability, but also on their chemical durability and
      persistency. In the use of MMVF, the goal is to decrease harmful effects of
      fibers by increasing their dissolution and removal from the lungs. The
      dissolution of Fe and Al from MMVF is more marked by rat alveolar macrophages
      (AMs) in culture than by mere medium, whereas medium is more effective than AMs
      in dissoluting silicon (Si) from MMVF, Fe and Al content of the fibers correlate
      negatively with the fiber Si dissolution by the AMs. Scanning electron
      micrographs show that MMVF are readily phagocytized by rat AMs in culture. The
      phagocytosis begins within 30 min after the onset of the exposure and continues
      for a 96-h observation period. Short fibers, less than 20 microns in length, are
      readily phagocytized by the AMs whereas longer fibers are attacked with a large
      number of AMs. MMVF induce also non-lethal changes in the rat AM surface
      morphology. Before exposure the cells have continuous membranes. The exposed AMs
      produce extensions which fasten them to the fibers or to other cells to form
      clumps or clusters of cells and fibers, each cell engulfing a part of a fiber.
      Over 70% of the exposed cells are viable after 96 h of exposure suggesting that
      MMVF are not acutely toxic rat AMs. MMVF also slightly damage cell membrane and
      increase the production of reactive oxygen species.

PMID- 9167056
TI  - Metabolism and excretion of polycyclic aromatic hydrocarbons in rat and in human.
AB  - Polycyclic aromatic hydrocarbons have shown to be an important class of
      environmental and occupational carcinogens. By balancing the carcinogenic
      potential PAH were found to predominantly contribute to the biological activity
      of environmental matter such as vehicle exhaust, used motor oil, and hard-coal
      combustion effluents. Due to the individual ratio of toxifying and detoxifying
      processes PAH-exposure measurements are not appropriate to be used for risk
      assessment without any further information on their metabolic fate. Accordingly,
      metabolite profiles of phenanthrene, pyrene, chrysene, benz(a)anthracene and
      fluoranthene have been recorded in both tar-pitch exposed Wistar rats and coke
      plant workers. The results show that metabolite profiles are invariant individual
      parameters which, however, vary from one individual to another. Significant
      differences with regard to the ratio of k-region and non-k-region hydroxylation
      of phenanthrene have been observed in a greater number of coke plant workers.
      This ratio might be helpful for risk assessment studies since it reflects the
      various cytochrome P450-dependent monooxygenase isoforms participating in the
      metabolism of PAH. Studies of this kind can only be carried out with substrates
      possessing several nonequivalent double bonds (phenanthrene, chrysene) whereas
      pyrene--commonly used for biomonitoring--does not satisfy this condition. The
      excretion rate (excretion versus exposure) seems to be an individual parameter.

PMID- 9167057
TI  - Dose response relationship between occupational PAH exposure and lung cancer--an
      overview.
AB  - Epidemiologic cohort and case-referent studies have shown an increased risk of
      lung cancer among various PAH-exposed occupations, such as coke, coal gas and
      aluminium production workers, road pavers, roofers and chimney sweeps. In
      different cohort studies, a positive dose response relationship between PAH
      exposure time and lung cancer have been described. On some workers, a
      relationship was found between coal for pitch volatiles (CTPV) and the risk of
      lung cancer. A doubling dose for lung cancer of > 20 [(mg CTPV/m3) years] or >
      100 [micrograms BaP/m3) years] has been found among coke and aluminium production
      workers. Acknowledgement of lung cancer as an occupational disease is proposed
      after a cumulative dose of > 20 [(mg CTPV/m3) years] or > 100 [micrograms BaP/m3)
      years].

PMID- 9167058
TI  - Interactive effects of polycyclic aromatic hydrocarbons and iron oxides
      particles. Epidemiological and fundamental aspects.
AB  - Iron oxides are present in many occupational atmospheres mainly in iron ore mines
      and in steel industry. Among these workers, epidemiological studies indicated an
      excess of lung cancer deaths. In mines, it was difficult to involve iron oxides
      exposure because there are other possible causes as radon, polycyclic aromatic
      hydrocarbon (PAH) present in diesel exhausts, silicosis or siderosis. The
      contradictory results of these studies are due to the differences of exposure
      levels or to the presence or not of these cofactors or of a sufficient
      prevention. But generally the results agree with an interaction of iron oxide
      dusts and smoking habits. It is unclear if this interaction supports an additive
      or multiplicative risk of lung cancer. Experimental studies with Fe2O3 showed
      that these particles are able to induce lung cancers only in the presence of PAH
      when administered to animals. In vitro studies permitted to observe an
      interaction in the metabolism of benzo(a)pyrene (BaP) leading to a higher level
      of precursors of the ultimate carcinogen. As this metabolism of BaP is known to
      be enhanced during lipoperoxidation, it is possible to involve this mechanism
      with Fe2O3. After phagocytosis and dissolution with production of ferric ions,
      Fe2O3 can enhance the production of reactive oxygen species responsible of
      damaging both lipidic constituents and DNA. Fe3O4 and mainly FeO may be more
      toxic, introducing directly ferrous ions in the cells after dissolution, but the
      cancerogenicity of the these compounds is unknown, making necessary to develop
      research.

PMID- 9167059
TI  - Scientific basis for an air quality standard on benzene.
AB  - The European Union is developing a comprehensive programme of air quality
      standards (AQS), including benzene. For that purpose, CONCAWE has reviewed the
      data to support a scientifically derived AQS for benzene and has concluded that
      30 ppb (96 micrograms/m3) as an annual TWA could be used as a basis. The
      conclusion is based on the NOAEL of acute myelocytic and monocytic leukaemia
      (AMML), which is considered to be the critical effect, derived from an
      occupational epidemiological mortality study, to which adjustment factors were
      applied.

PMID- 9167060
TI  - Induction of nitric oxide synthase by chlorinated pesticides (p,p'-DDT,
      chlordane, endosulfan) in rat liver.
AB  - The aim of this study is to investigate the effect of certain polychlorinated
      pesticides on the induction of rat liver Ca(2+)-independent nitric oxide synthase
      (NOS) and compare it with the effect of bacterial lipopolysaccharide. Our results
      show that endosulfan and p, p'-DDT treatment significantly increases the NOS
      activity while no significant induction by any route of administration was
      observed in the case of chlordane. Our results show therefore that a wide variety
      of chlorinated pesticides, which are considered as hepatic tumor promotors, can
      stimulate the expression of NO synthase in vivo.

PMID- 9167061
TI  - Study of mercury content in edible mushrooms.
AB  - The influence of time and temperature of mineralisation of mushrooms was studied
      for mercury determination by cold vapor atomic absorption. Optimal conditions for
      a complete mercury recuperation were obtained using a mixture of nitric and
      sulphuric acid (6 ml HNO3, 4 ml H2SO4) in presence of KMnO4 (3 ml of a 0.44 M
      solution) at 95 degrees C for 4 h, with 1 g wet sample. The detection limit of
      method was 3.2 ng/g. These conditions have shown high reproductibility and
      accuracy.

PMID- 9167062
TI  - Rapid method for analysis of chloroacetanilide and chloronitrophenoxyaniline
      herbicides by gas chromatography.
AB  - The herbicides Alachlor and Alclonifen are recently used in France for pre
      emergent weed control in corn, essentially in association. For this reason, an
      improved method has been developed by gas chromatography for simultaneously
      characterising and quantifying the two herbicides. The best conditions were
      obtained by using a gas chromatograph equipped with an ion trap detector, and a
      30 m x 0.25 mm DB-1701 fused silica capillary column. Retention times of Alachlor
      and Aclonifen were 12.8 and 23.2 min respectively. The limit of detection was of
      2.0 ppb for each herbicide.

PMID- 9167063
TI  - Determination of total mercury in estuary, lake and river sediments.
AB  - In order to improve the quality of the results in sediment analysis, the
      Community Bureau of Reference (BCR) of the European Communities has developed 3
      sediment reference materials (CRM) from estuarine, lake and river origins.
      Certification of mercury content in these materials was achieved by 3 methods
      (cold vapor atomic absorption spectrometry, plasma emission spectrometry, neutron
      activation analysis with radiochemical separation). The values finally certified
      in the CRM estuarine, lake and river sediments are 1.77 +/- 0.06, 0.67 +/- 0.02,
      1.03 +/- 0.13 mg/kg respectively.

PMID- 9167064
TI  - Effects of irritants on airways reactivity.
AB  - The authors observed reactivity changes of airways smooth muscles after exposure
      of experimental animals to toluene and hyperoxia. The pretreatment with
      antioxidants did not prevent these changes.

PMID- 9167065
TI  - Toxicity of ferric oxide and benzo[a]pyrene alone or in combination in
      respiratory tract of Sprague Dawley rats.
AB  - The association of small quantities of ferric oxide with Benzo[a]Pyrene (BaP)
      appears to increase in vivo the toxic effect of BaP. The effect of Fe2O3 may be
      mediated by the recruitment of alveolar macrophages. These cells would contribute
      to the production of toxic and carcinogenic BaP metabolites and would stimulate
      development of tumors by producing cellular mediators of inflammation. In order
      to understand the mechanism of the synergic effect, we have instillated male
      Sprague Dawley rats 3 weeks of age with a single dose: Fe2O3 (3 mg) or BaP (3
      mg)/combination Fe2O3-BaP (3 mg-3 mg) in 200 microliters of physiological saline
      solution. Control group of identical size (treated with physiological saline
      solutions and untreated) were used for this study. Animals were sacrificed 48
      hours after instillation and a bronchoalveolar lavage (BAL) was performed. With
      each BAL we have obtained protein measurement, cells were stained with May
      Grunwald-Giemsa method and slides were studied with polarised light. The
      malonaldehyde (MDA) was measured by High Performance Liquid Chromatography. The
      PMN elastase determination was performed by IMAC (immuno-activation) technology.
      An automated kinetic method for measuring cathepsins B and L was carried out
      using a fluorogenic substrate: Z-Phe-Arg-AMC, a specific inhibitor E64 and AMC as
      an internal standard. After a quantitative Dot-Blot of the samples of BAL, an
      immunodetection of alpha(1)-antitrypsin (alpha(1)AT) was performed. The
      inhibitory capacity of alpha(1)AT was determined by an enzymatic reaction with
      porcine pancreatic elastase. We have observed an increased MDA level for rats
      intoxicated with Fe2O3 (123%), BaP (31%) and Fe2O3 + BaP (56%). The levels of PMN
      elastase and cathepsin B and L were increased: Fe2O3 (51-58%), BaP (52-27%). This
      effect was not seen for rats intoxicated by Fe2O3 + BaP. The free alpha(1)AT was
      decreased with the three toxics (Fe2O3: 44%--BaP: 42%--Fe2O3: 41%). The
      inhibitory capacity of alpha(1)AT was lower in groups of rats instilled with
      toxics.

PMID- 9167066
TI  - Toxicity of iron oxides and metabolites of benzo[a]pyrene alone or in combination
      in cells culture and identification by laser microprobe mass spectrometry.
AB  - The goal of the gas-phase studies of well-characterized transition-metal systems
      is to enhance our understanding of the chemistry and sometimes of the toxic,
      carcinogenic effects of transition metal oxide clusters and compounds. The
      analysis of inorganic solids by time of flight laser microprobe mass spectrometry
      (TOF-LMMS) shows the formation of clusters in the mass spectra which can be used
      for the identification of inorganic particles. First, we have applied non
      resonance ionization (delta = 226 nm) or resonant ionization (delta = 293.7 nm)
      of iron to study the non stoichiometric Fe1-xO, Fe3O4, Fe2O3 compounds in
      positive mode by TOF-LMMS. The positive mass spectra are characterized by many
      differences between the clusters detected and their intensities. Then, we have
      analysed the benzo[a]pyrene (BaP), the 1-hydroxbenzo[a]pyrene (1-OH-BaP) and the
      3-hydroxybenzo[a]pyrene (3-OH-BaP) of TOF-LMMS and by Fourier Transform Irons
      Cyclotron Resonance Mass Spectrometry (FT-ICR-MS). It is possible to distinguish
      these different compounds by their respective fingerprint. Later on, we have
      studied toxic effects of iron oxides (Hematite Fe2O3 and Magnetite Fe3O4),
      benzo[a]pyrene (BaP) and Pyrene, alone or in combination. The LC50 was
      appreciated by colony-forming cell culture method. Cells were observed by
      electron microscopy and the valence of particles was analysed by TOF-LMMS. With
      Fe2O3 we have observed a significant decrease (20%) at higher concentration (0.5
      mmol/l) and smaller quantities of BaP were highly toxic. The association of BaP
      at the LC10 dose (0.05 mumol/l) with growing doses of Fe2O3 or Fe3O4 (0.0125;
      0.025; 0.05; 0.1; 0.2 mmol/l), appeared to increase the toxic effect of BaP 3 to
      4 times. These results suggest that Fe2O3 and Fe3O4 alone are not very toxic but
      the association of one of these compounds with BaP increases the toxicity of the
      latter. On the other hand, TOF-LMMS seems to show a metabolization of iron oxide
      into reduced form. But, it is necessary to raise the ambiguity about the iron
      which is always in the cells present. For that purpose, studies with iron oxides
      enriched by 54Fe isotope have begun.

PMID- 9167067
TI  - Musculature of the soft palate: clinico-anatomic correlations and therapeutic
      implications in the treatment of cleft palates.
AB  - OBJECTIVE: Hypoplasia of the maxilla, often described as a classic sequela to
      surgical repair of the cleft palate, has been rare in our experience. We believe
      that our surgical technique, which includes dividing the nasal mucosa and the
      abnormal muscular insertions at the posterior border of the hard palate, is an
      important factor in preventing this sequela. METHOD: We compared the anatomy of
      12 normal palates in cadavers to the anatomy of cleft palates seen at operation
      and to the anatomy of one cleft palate in a fetus aged 34 weeks. RESULTS: In
      cleft palates, the muscular fibres have an abnormal sagittal orientation,
      inserting on the posterior border of the hard palate. CONCLUSION: The division of
      both the nasal mucosa and these abnormal muscular insertions at the posterior
      border of the hard palate enables the surgeon to eliminate the abnormal posterior
      pull of these fibers on the maxilla.

PMID- 9167068
TI  - Radiographic assessment of secondary autogenous alveolar bone grafting in cleft
      lip and palate patients.
AB  - OBJECTIVE: To assess if a 4-point, radiographically based scale could be used
      between operators to reliably assess the success of secondary alveolar bone
      grafting. DESIGN: The study was retrospective with the clinicians blind to
      patient identity. Radiographs were examined twice by two clinicians with 1 week
      between assessments. SETTING: The research was carried out in a hospital-based
      orthodontic/oral and maxillofacial unit. PATIENTS: All patients who had secondary
      alveolar bone grafting in this unit between February 1992 and March 1995 were
      included in this study. There were 38 patients with a total of 48 grafted sites.
      INTERVENTIONS: The bone graft site was radiographed following orthodontic
      expansion prior to grafting. The radiograph was repeated postoperatively at a
      mean of 4 months after surgery. MAIN OUTCOME MEASURE: The degree of bony fill in
      the cleft area was assessed using a 4-point scale: Grade 1 > 75% bony fill; Grade
      2 50-75% bony fill; Grade 3 < 50% bony fill; Grade 4 no complete bony bridge.
      RESULTS: Overall, 50% of grafts achieved grade 1, 23% were grade 2, 22% grade 3,
      and 5% grade 4. Levels of intra- and inter-observer agreement were highly
      variable (.33 to .72 kappa statistic). CONCLUSIONS: The 4-point scale described
      could be used to assess the success of autogenous secondary alveolar bone
      grafting. It showed moderate to substantial intra-observer agreement, and fair-to
      moderate inter-observer agreement.

PMID- 9167069
TI  - Comparison of 2-D calculations from periapical and occlusal radiographs versus 3
      D calculations from CAT scans in determining bone support for cleft-adjacent
      teeth following early alveolar bone grafts.
AB  - OBJECTIVE: This investigation was conducted to determine the agreement between
      three-dimensional (3-D) calculations from CAT scans and two-dimensional (2-D)
      calculations from standard dental radiographs in evaluating bone support for
      cleft-adjacent teeth after primary bone grafting. DESIGN: This retrospective
      study utilized CAT scans and dental radiographs taken of the alveolar cleft in
      patients an average of 11 years after primary bone grafting. SETTING: The
      subjects were patients treated by the Cleft Palate Team at Children's Memorial
      Hospital and Loyola University Medical Center, Chicago, Illinois. PATIENTS:
      Fourteen UCLP patients (9 males, 5 females) agreed to participate in this study
      by undergoing CAT scan assessment of their alveolar cleft sites. They also had to
      have periapical or occlusal radiographs of the grafted cleft site taken within 6
      months of the CAT scan. INTERVENTIONS: All patients underwent primary lip repair,
      placement of a passive palatal plate, primary alveolar bone grafting (mean age
      6.4 months), and palatoplasty before 1 year of age. Major tooth movement through
      final orthodontics was completed by the time of the radiographic assessment. MAIN
      OUTCOME MEASURES: CAT scan sections were reformatted and reconstructed to three
      dimensionally calculate the percentage of root covered by bone support for the 15
      teeth adjacent to the graft cleft sites. Dental radiographs of the same teeth
      were also traced and digitized. Percentages of root supported by bone were also
      established using the dental radiographs by dividing the amount of root covered
      by bone, by the anatomic root length. RESULTS: A paired, two-sample t test
      revealed no significant differences between the two methods of assessment, while
      linear regression showed a statistically significant correlation between the CAT
      scan assessment and the percentages found on the radiographs. CONCLUSIONS:
      Routine dental radiographs were able to estimate the total 3-D bone support for
      the roots of cleft adjacent teeth as determined by CAT scan to a statistically
      significant degree when groups where compared. The clinical significance for
      evaluation of individual cases was less impressive with a wide range of
      variability and a level of agreement that required acceptance of differences up
      to 25%.

PMID- 9167071
TI  - Embryologic features of term fetuses and newborns in CL/Fr mice with special
      reference to cyanosis.
AB  - OBJECTIVE: The objective of this study was to clarify the embryologic features of
      CL/Fr mice in relation to cyanosis. METHOD: Orofacial examinations were conducted
      on 18-day-old term fetuses and newborns. Except for open eyelids in a few cases,
      all of the external abnormalities in this strain were cleft lip and/or palate
      (CLP). RESULTS: The CLP incidence in term fetuses was 28.4%. The body and
      placental weights were not different between CLP(+) and CLP(-) fetuses. Several
      types of CLP were found; the most frequent was bilateral complete CLP (60%)
      followed by left complete (16%). Bilateral complete CL, which is the most severe
      CL type, was associated with poorly developed secondary palate and wide cleft. In
      newborns, 39.4 % of CLP(+) mice showed cyanosis, where no CLP(-) mice had such
      signs. The body weight of cyanotic mice with CLP was significantly lighter than
      that of noncyanotic mice with CLP. Cyanotic mice had severe types of CLP and
      unelevated palatal shelves. CONCLUSION: We suggest that mechanical airway
      obstruction may be one of the causes of cyanosis in newborn CL/Fr mice.

PMID- 9167070
TI  - Maternal cigarette smoking and oral clefts: a meta-analysis.
AB  - OBJECTIVE: A meta-analysis was performed to estimate the association between
      maternal cigarette smoking and the risk of having a child with a nonsyndromic
      oral cleft (NSOC). DESIGN: Studies published from 1966 through 1996 were
      retrieved using MEDLINE, Current Contents, bibliographies, and other sources.
      MEDLINE and Current Contents search terms included "oral clefts," "cigarette
      smoking," "birth defects," and "congenital malformations." Cohort and case
      control studies that enrolled oral cleft patients [cleft lip with or without
      cleft palate (CL/P), cleft palate (CP), or both] and controls, and presented
      information on maternal cigarette exposure during pregnancy were included in the
      analysis. Descriptive and outcome data from each study were independently
      abstracted by two authors. RESULTS: The overall odds ratio of the 11 studies
      satisfying criteria was 1.29 [95% confidence interval (CI), 1.18 to 1.42] for
      CL/P and 1.32 (95% CI: 1.10 to 1.62) for CP, indicating a small increase risk of
      having a child with either a CL/P or a CP for mothers who smoke during the first
      trimester of the pregnancy. CONCLUSIONS: These analyses suggest a small but
      statistically significant association between maternal cigarette smoking during
      the first trimester of gestation and increased risk of having a child with a CL/P
      or CP.

PMID- 9167072
TI  - Development of infants and toddlers with clefts from birth to three years of age.
AB  - OBJECTIVE: The purpose of this study was to use caregiver report measures to
      describe the developmental status of infants and toddlers with clefts. METHOD:
      Developmental assessment data were obtained on 186 infants and toddlers with
      cleft lip (n = 48), cleft palate (n = 46), and cleft lip/palate (n = 92) at one
      of the following age categories: 5 months (n = 47), 13 months (n = 46), 25 months
      (n = 47), and 36 months (n = 46). Developmental assessment measures used were the
      Kent Infant Developmental Scale and the Minnesota Child Development Inventory,
      both caregiver reports. Data were analyzed in separate 2-between ANOVAs (age x
      cleft type) for each developmental domain according to developmental assessment
      measure. Further, results were examined relative to the normative sample.
      RESULTS: The ANOVA results indicated that at 5 months, lower motor and self-help
      developmental quotients (DQs) were evident compared to the 13-month-old level.
      When compared to the normative sample, the 5-month-old infants exhibited 'at
      risk/delayed' development on the motor, self-help, and cognitive domains, and as
      reflected on their full-scale scores, depending on the cleft type. Infants at 13
      and 25 months were within normal limits in all developmental domains, with the
      exception of the 13-month-old infants with cleft palate, who demonstrate 'at
      risk' development in the motor domain. At 36 months of age, all toddlers
      demonstrated significantly lower developmental performance in the fine motor,
      gross motor, and expressive language domain compared to the 25-month-old
      toddlers. Toddlers with cleft palate exhibit 'at-risk/delayed' development in the
      expressive language domain at 36 months. CONCLUSION: Data are discussed relative
      to the events surrounding team management of clefts, including surgery, middle
      ear problems, and feeding difficulty.

PMID- 9167074
TI  - Mandibular and maxillary asymmetry in individuals with unilateral cleft lip and
      palate.
AB  - OBJECTIVE: This study was conducted to evaluate the degree of maxillary and
      mandibular asymmetry in the verticle and transverse planes seen in
      posteroanterior cephalometric radiographs relative to chronologic age in
      postoperative complete UCLP patients compared to controls. METHOD: Mandibular and
      nasomaxillary asymmetry was retrospectively studied in complete unilateral cleft
      lip and palate (UCLP) and noncleft individuals (controls) by means of
      posteroanterior cephalometric analysis. All the UCLP patients available (total
      40) and randomly selected noncleft controls (total 142) were included in the
      study. The UCLP patients had undergone lip and palate reconstruction in Strong
      Memorial Hospital, University of Rochester, Rochester, New York, and orthodontic
      treatment in the Department of Orthodontics, Eastman Dental Center, Rochester,
      New York. The controls were selected based on the age that treatment was
      initiated and were treated in the department for various malocclusions; none had
      undergone maxillary expansion or surgical treatment. The asymmetry assessed on
      mixed longitudinal records of the patients with UCLP was analyzed relative to
      three chronologic age groups and compared to the controls. In addition,
      mandibular asymmetry was correlated to maxillary asymmetry in UCLP individuals to
      investigate possible growth patterns between the two jaws. RESULTS: Mandibular
      asymmetry in UCLP individuals was found to increase with growth and time and
      peaked at post-pubertal growth-spurt stages. The cleft subjects were more
      asymmetric than controls in all stages of growth. Mandibular asymmetry followed
      the affected maxilla closely, indicating a parallel growth pattern of the jaws.
      CONCLUSION: The unilateral cleft lip and palate patients manifested asymmetry of
      the mandible. This asymmetry develops in a parallel pattern with the affected
      maxilla, suggesting that early evaluation and treatment of the anomalies in the
      nasomaxillary skeleton as well as in the mandible is necessary when treating
      unilateral cleft lip and palate individuals.

PMID- 9167073
TI  - Satisfaction with facial appearance among subjects affected by a cleft.
AB  - OBJECTIVE: This study examined the satisfaction of patients with clefting and
      their parents with facial appearance and how this alters with age. The
      relationship between satisfaction with appearance and psychosocial functioning
      was also examined. DESIGN: Prospective SETTING: Subjects were recruited for the
      study from nine hospital-based clinics. PARENTS, PARTICIPANTS: All subjects has
      some type of cleft and were 10, 15 or 20 years of age. In all, 111 subjects with
      clefting and 62 parents were included. MAIN OUTCOME MEASURES: Facial appearance
      was rated on a subjective ordinal scale of 1 to 7; psychosocial adjustment was
      measured with the Childhood Experience Questionnaire. RESULTS: Self-satisfaction
      with appearance among the 10- and 15-year-old subjects correlated with their
      psychosocial adjustment (p = .027). The 20-year-old subjects were, on average,
      significantly more satisfied with their appearance than the 10- and 15-year-olds
      (p = .009 and p = .012, respectively). However, some 20-year-old subjects
      remained greatly dissatisfied with aspects of their facial appearance. Subjects
      with visible anomalies were significantly more dissatisfied with their appearance
      than subjects with invisible anomalies (p = .035). The 15-year-old subjects were
      identified as being significantly more dissatisfied with appearance than their
      parents (p = .005). CONCLUSIONS: Subjects affected by a cleft with visible
      impairments are more dissatisfied with their facial appearance than are subjects
      with invisible impairments. Satisfaction with facial appearance among 10- and 15
      year-old subjects with a cleft may be associated with their self-reported levels
      of psychosocial functioning. Measuring self-satisfaction with appearance may help
      to identify subjects at risk from adjustment problems.

PMID- 9167075
TI  - The jaw index: new guide defining micrognathia in newborns.
AB  - OBJECTIVE: Newborns with glossoptosis due to micrognathia can suffer from life
      threatening respiratory distress and severe feeding difficulties. These
      characteristic features are found in newborns with Pierre Robin sequence. In the
      relevant literature, no concensus concerning diagnosis for these children can be
      found. A guide defining micrognathia can be helpful in the diagnosis of
      glossoptosis and possible airway obstruction. METHOD: The jaw index is obtained
      in newborns by measuring three facial dimensions. In a series of 100 healthy
      neonates the standard measures were defined. RESULTS: The average jaw index in
      children with Pierre Robin sequence differs significantly from the reference
      group and was found to be over 3.6 times the normal value. CONCLUSIONS:
      Micrognathia can be defined with the jaw index.

PMID- 9167076
TI  - A new index for assessing surgical outcome in unilateral cleft lip and palate
      subjects aged five: reproducibility and validity.
AB  - OBJECTIVE: This study assessed the reproducibility, reliability, and predictive
      validity of a previously developed index by the authors for assessing surgical
      outcome in unilateral cleft lip and palate (UCLP) children aged 5. METHODS: Sixty
      randomly selected study models of 5- to 6-year-old complete UCLP subjects were
      obtained and the index was used to assess their surgical outcomes. RESULTS:
      Assessment of these study models using the new index demonstrated excellent intra
      examiner agreement. The inter-examiner agreement was shown to be good. The
      corresponding longitudinal models at 16 to 18 years of 54 of the initial 5- to 6
      year-old sample were also acquired. These subjects had undergone orthodontic
      treatment but not orthognathic surgery. The need for osteotomy amongst these
      models was assessed. Between 13% and 18% (depending on examiner) of 5-year-olds'
      models were scored in the groups likely to require orthognathic surgery. In the
      corresponding 16- to 18-year-olds' models, 9% were assessed as likely to benefit
      from an osteotomy. However, on an individual basis, it was not possible to
      predict future growth from study models at age 5. CONCLUSIONS: This study has
      provided a reliable and reproducible index for assessing the outcome of surgery
      in UCLP subjects earlier than indices already available. True validation of the
      index was not possible but it appears that it relies on face validity.

PMID- 9167077
TI  - Evaluation of the results of cleft lip and palate surgical treatment: preliminary
      report.
AB  - OBJECTIVE: The aim of this study was to present a measuring tool, in the form of
      a dual-rating grid, for preoperative appearance and postoperative results in the
      treatment of labionasal clefts. METHODS: This study was carried out on 43
      children with partial unilateral clefts, operated on using a derivation of
      Millard's technique. The preoperative initial severity score (ISS) was the sum of
      points each corresponding to a precise anatomic anomaly. A severe cleft was given
      a rating of 6, and a mild cleft a rating of 1. The postoperative results score
      (PRS) was the sum of points corresponding to residual or acquired anatomic
      anomalies: a good result was given 0.5, and a poor result 3.5. Each score was a
      mark given separately and agreed on by two surgeons. To compare the rating grids,
      the correlation between the ISS and the PRS was calculated. RESULTS: Twenty-four
      patients had an ISS less than 5; 19 patients had an IGS more than or equal to 5.
      Marks for the PRS were between 0.5 and 3.5 with the majority at 1 to 1.5.
      CONCLUSION: This study demonstrates the coherent connection between these two pre
      and postoperative rating grids.

PMID- 9167078
TI  - Robin sequence: obstructive sleep apnea following pharyngeal flap.
AB  - OBJECTIVE: We reviewed 24 children with Robin sequence who underwent cleft palate
      repair. METHOD: All patients were 5 years of age or older at the time of review,
      allowing for accurate assessment of speech in relation to velopharyngeal
      function. All infants had palatal closure between 9 and 14 months of age, either
      V-Y repair (n = 16) or von Langenbeck repair (n = 8). RESULTS: Only 1 of 16
      children who had V-Y repair had borderline velopharyngeal dysfunction (VPD). For
      reasons that are unclear, in the von Langenbeck repair group, six of eight
      children had VPD, and four of six underwent pharyngeal flap. Three additional
      patients with nonsyndromic Robin sequence had palatoplasty and subsequent
      pharyngeal flap. Six of the combined total of seven children with nonsyndromic
      Robin sequence developed obstructive sleep apnea and require flap take-down.
      CONCLUSION: Since conventional pharyngeal flap for VPD in nonsyndromic Robin
      sequence children resulted in a high incidence of obstructive sleep apnea,
      alternative management should be considered: modification of the standard
      pharyngeal flap, palatal lengthening (V-Y or double-opposing Z-plasty), or
      construction of a speech bulb.

PMID- 9167079
TI  - Relationship between lower-lip fistulae and cleft lip and/or palate in Von der
      Woude syndrome.
AB  - OBJECTIVE: This study was conducted to evaluate the relationship between fistulae
      of the lower lip and cleft lip and/or palate in patients with Van der Woude
      syndrome. METHODS: The medical records of 11,000 patients with cleft lip and/or
      palate registered at the Cleft Lip-Palate Research and Rehabilitation Hospital,
      University of Sao Paulo, Bauru were reviewed. Of these patients, 133 (1.2%)
      presented with Van der Woude syndrome. RESULTS: Of the 133 patients, 88 (66.2%)
      exhibited full clefts, 22 (16.5%) only cleft lip, and 23 (17.3%) only cleft
      palate. The lower-lip fistulae observed in these 133 patients were bilateral
      symmetric in 66 (49.7%), bilateral asymmetric in 42 (31.6%), microform in 19
      (14.3%), median in 5 (3.8%), and unilateral in 1 (0.7%). CONCLUSION: This
      population sample appears to exhibit the previously published tendency for
      bilateral, unilateral, or mixed-type congenital fistulae to be associated with
      cleft lip with or without cleft palate, while so-called microforms or conic
      elevations are almost exclusively associated with cleft palate.

PMID- 9167080
TI  - Magnetic resonance angioplasty for prepharyngoplasty assessment in
      velocardiofacial syndrome.
AB  - OBJECTIVE: The assessment of the posterior pharyngeal vasculature in
      velocardiofacial syndrome has been traditionally based on endoscopic
      visualization of pulsations or conventional angiography. This case report
      describes the utility of presurgical imaging with magnetic resonance angiography
      (MRA) prior to performing pharyngoplasty. CONCLUSION: The use of the MRA data
      presurgically is an effective way to prevent bleeding complications during
      pharyngoplasty.

PMID- 9167081
TI  - Use of an osseointegrated implant for dental rehabilitation after cleft repair by
      periosteoplasty: a case report.
AB  - OBJECTIVE: We report here on a patient with unilateral cleft lip and alveolus who
      underwent dental rehabilitation of cleft alveolus using an osseointegrated
      implant after cleft repair by periosteoplasty. The patient, whose lateral incisor
      was congenitally missing, had periosteoplasty, followed by excellent bone
      formation at the cleft alveolus within 2 years. After the completion of
      orthodontic alignment of the maxillary dental arch, a Branemark single-tooth
      implant was placed into the bone-formed alveolus. CONCLUSION: This treatment
      procedure offers an option of dental rehabilitation for the alveolar clefts of
      patients with cleft lip and/or palate.

PMID- 9167082
TI  - A Bayesian formulation of the Kalman filter applied to the estimation of
      individual pharmacokinetic parameters.
AB  - A general method of Bayesian forecasting employing the dynamic linear model has
      been adapted to the problem of estimating individual pharmacokinetic parameters.
      The Bayesian forecasting method incorporates an efficient Kalman filter algorithm
      for updating pharmacokinetic parameter estimates when further observations are
      made. The Kalman filter is more general and flexible than other Bayesian methods
      currently used and simulation studies have demonstrated its practicality for
      three different pharmacokinetic models. The method serves as the basis for a
      computer program for general clinical use.

PMID- 9167083
TI  - Procedure for estimating the correlation dimension of optokinetic nystagmus
      signals.
AB  - In this study, optokinetic nystagmus (OKN) is hypothesized to be controlled by a
      low-dimensional deterministic and possibly chaotic generator. A procedure for
      quantifying the presumably low-dimensional structure of the OKN signal, based on
      the Singular Spectrum Approach and the Grassberger--Procaccia algorithm for
      estimating the correlation dimension, v, is described. The procedure developed
      showed robustness against noise. Applying this method to OKN signals from 10
      healthy subjects and 10 patients suffering from vertigo showed a statistically
      significant lower mean v value for the patients.

PMID- 9167084
TI  - Analysis of the effect of apex-base wall curvature on the vectorial
      representation of ventricular depolarization: a model study.
AB  - A computer model of propagated activation study is presented to investigate the
      possible effect of the ventricular wall curvature on the vectorial representation
      of its activation. The shape of the ventricle is changed by gradually decreasing
      the value of the input parameter determining the relative apex-base curvature of
      the ventricular wall (rvc) from 1.0 to 0.5. Two series of simulation experiments
      were accomplished. In the first series all input parameters of the model were
      held constant, except for rvc. In the second series, the height of the ventricles
      was altered simultaneously with the value of rvc in order to hold the volumes of
      the ventricular walls and cavities constant. In both series, the gradual increase
      of the apex-base curvature of the ventricular walls led to a slight decrease of
      initial heart vectors and an increase of laterally oriented vectors accompanied
      with their downward deviation. In addition, this increase caused a decrease in
      the terminal heart vectors along with their rotation to the left. The degree of
      this changes was proportional to the difference in the relative apex-base
      curvature of the two ventricles compared. The apex-base curvature of ventricular
      walls was found to be an effective factor influencing the cardiac electric field
      and consequently its representative quantitative parameters.

PMID- 9167085
TI  - A general statistical framework for frequency-domain analysis of EEG topographic
      structure.
AB  - A wide variety of rhythmic electrophysiological phenomena--including driven,
      induced, and endogenous activities of cortical neuronal masses--lend themselves
      naturally to analysis using frequency--domain techniques applied to multichannel
      recordings that discretely sample the overall spatial pattern of the rhythmic
      activity. For such cases, a large but so far poorly utilized body of statistical
      theory supports a third major approach to topographic analysis, complementing the
      more familiar mapping and source-recovery techniques. These methods, many of
      which have only recently become computationally feasible, collectively provide
      general solutions to the problem of detecting and characterizing systematic
      differences that arise--not only in the spatial distribution of the activity, but
      also in its frequency-dependent between-channel covariance structure--as a
      function of multiple experimental conditions presented in conformity with any of
      the conventional experimental designs. This application-oriented tutorial review
      provides a comprehensive outline of these resources, including: (1) real
      multivariate analysis of single-channel spectral measures (and measures of
      between-channel relationships such as coherence and phase), (2) complex
      multivariate analysis based on multichannel Fourier transforms, and (3) complex
      multivariate analysis based on multichannel parametric models. Special emphasis
      is placed on the potential of the multichannel autoregressive model to support
      EEG (and MEG) studies of perceptual and cognitive processes.

PMID- 9167086
TI  - Multifarious system for quantitative analysis of histologic compartments.
AB  - A system is presented for measuring relative volumes of histologic compartments
      in microscopic slides. The computer program for that system was written by us as
      an MS windows 3.x application. The applied method of measurements, based on the
      "point-counting" technique, requires the recognition of the compartments,
      corresponding to the selected points of an image. The neural network was employed
      to facilitate the process of classification of the examined points. Nine
      descriptors of an image were selected as an input to the network (a pattern).
      Error-free compartment recognition was not always achieved because of some
      overlapping of the pattern classes. Nevertheless, the semi-automation of the
      assignment of the examined points to histologic compartments makes the
      measurements less laborious and time-consuming.

PMID- 9167087
TI  - Pioneers in oral biology: the migrations of Gottlieb, Kronfeld, Orban, Weinmann,
      and Sicher from Vienna to America.
AB  - Following the annexation of Austria by Hitler's Germany in 1938, officials at the
      eminent University of Vienna Medical School purged faculty ranks of Jews. Among
      those forced out were several distinguished physician dentists, several of whom
      emigrated to the United States. The assimilation of foreign-trained dentists
      raised questions at national meetings of the AADS and the National Association of
      Dental Examiners. Already existing ties between dental schools in Chicago and the
      University of Vienna, including the 1928 appointment of Rudolf Kronfeld to the
      faculty at Loyola, led to the relocation of Balint Orban, Harry Sicher, and
      Joseph Peter Weinmann in that city. Bernhard Gottlieb, who had been director of
      the Dental Institute in Vienna, transplanted less easily, but eventually found a
      niche at the Baylor College of Dentistry in Dallas. The careers of the Vienna
      dentist-scientists strengthened the scientific foundations of clinical dentistry
      in the United States, contributed to the development of a stronger research
      establishment, and enlarged the scope of oral biology.

PMID- 9167088
TI  - Managed care and dental education and research: should academicians be concerned?
AB  - This paper examines the restructuring of the delivery system resulting from
      managed care. As HMOs consolidate to a few large companies in urban areas, they
      put great pressure on medical providers to reduce their costs and excess delivery
      capacity. In this environment, academic health centers face serious problems,
      because HMOs are reluctant to pay their higher charges, and public educational
      subsidies are declining. Managed care is unlikely to have the same impact on
      dentistry. Although managed dental care is growing, most Americans will not be
      enrolled, since they do not have dental insurance. Also, the supply of dentists
      is starting to decline, increasing the relative demand for dental services.
      Managed care will have only a limited direct impact on most dental schools, but a
      significant indirect effect. As academic health center budgets are reduced, all
      health professional schools can expect to contribute to solving the financial
      problems of University hospitals and medical schools. The response of dental
      academicians to these challenges will determine the future of dental education
      and research for the next decade. Bold new initiatives are needed to find new
      sources of revenue to support educational and research programs.

PMID- 9167089
TI  - The effect of fluoride on apatite structure and growth.
AB  - Fluoride participates in many aspects of calcium phosphate formation in vivo and
      has enormous effects on the process and on the nature and properties of formed
      mineral. The most well-documented effect of fluoride is that this ion substitutes
      for a column hydroxyl in the apatite structure, giving rise to a reduction of
      crystal volume and a concomitant increase in structural stability. In the process
      of enamel mineralization during amelogenesis (a unique model for the cell
      mediated formation of well-crystallized carbonatoapatite), free fluoride ions in
      the fluid phase are supposed to accelerate the hydrolysis of acidic precursor(s)
      and increase the driving force for the growth of apatitic mineral. Once fluoride
      is incorporated into the enamel mineral, the ion likely affects the subsequent
      mineralization process by reducing the solubility of the mineral and thereby
      modulating the ionic composition in the fluid surrounding the mineral, and
      enhancing the matrix protein-mineral interaction. But excess fluoride leads to
      anomalous enamel formation by retarding tissue maturation. It is worth noting
      that enameloid/enamel minerals found in vertebrate teeth have a wide range of CO3
      and fluoride substitutions. In the evolutionary process from elasmobranch through
      enameloid to mammalian enamel, the biosystems appear to develop regulatory
      functions for limiting the fluoridation of the formed mineral, but this
      development is accompanied by an increase of carbonate substitution or defects in
      the mineral. In research on the cariostatic effect of fluoride, considerable
      emphasis is placed on the roles of free fluoride ions (i.e., preventing the
      dissolution and accelerating the kinetics of remineralization) in the oral fluid
      bathing tooth mineral. Fluoride also has been used for the treatment of
      osteoporosis, but much still remains to be learned about maximizing the benefit
      and minimizing the risk of fluoride when used as a public health measure.

PMID- 9167090
TI  - Tissue engineering, morphogenesis, and regeneration of the periodontal tissues by
      bone morphogenetic proteins.
AB  - Tissue engineering is the emerging field of science developing techniques for
      fabrication of new tissues for replacement based on principles of cell and
      developmental biology and biomaterials. Morphogenesis is the cascade of pattern
      formation and the attainment of form of the various organs and the organism as a
      whole. The periodontium consist of the periodontal ligament, cementum, and
      alveolar bone. Bone has considerable potential for regeneration and therefore is
      a prototypic model for tissue engineering. The three main ingredients for tissue
      engineering are regulatory signals, responding stem cells, and extracellular
      matrix. Recent advances in molecular biology of the bone morphogenetic proteins
      (BMPs) have set the stage for tissue engineering of bone and related tissues,
      including the periodontium. Bone-derived BMPs, with a collagenous matrix as
      carrier, induced cementum and alveolar bone regeneration in surgically created
      furcation defects in the primate. It is noteworthy that there was morphogenesis
      of periodontal ligament and a faithful insertion of Sharpey's fibers into
      cementum. In the same furcation model, recombinant human osteogenic protein-1
      (rhOP-1, also known as BMP-7), in conjunction with the collagenous carrier,
      induced extensive cementogenesis with insertion of Sharpey's fibers into the
      newly formed cementum. The observation that BMPs induce cementogenesis and
      periodontal ligament formation indicates that these proteins may have multiple
      functions in vivo not limited to cartilage and bone induction. The rapid advances
      in the molecular biology of BMPs and their receptors bode well for novel
      strategies to engineer the regeneration of the periodontal tissues.

PMID- 9167091
TI  - Subgingival delivery of therapeutic agents in the treatment of periodontal
      diseases.
AB  - This article reviews the current status of controlled local delivery of
      antibacterial agents in the treatment of periodontitis. The principle of local
      intrapocket delivery of antibacterial agents and their delivery are discussed.
      The dosage forms include fibers, film/slabs, and injectable systems, some of
      which are degradable, while others are not and need to be removed at the
      termination of the treatment. The antibacterial agents used cover a range of
      antibiotics as well as antiseptics, and the composition of the delivery systems,
      their reported use, and the clinical results are summarized. The use of these
      systems in clinical practice is relatively recent, and therefore their
      application and integration into the dental office are not yet clearly defined.
      Clinical applications that have been tested are critically reviewed, and clinical
      situations in which controlled delivery of antibacterial agents may prove to be
      clinically useful are suggested for scientific evaluation.

PMID- 9167093
TI  - Graft-vs.-host disease.
AB  - Bone marrow transplantation (BMT) is the treatment of choice for many leukemias,
      lymphomas, bone marrow failure syndromes, and immunodeficiency disorders, and is
      the primary and salvage therapy for many solid malignancies. With the
      establishment of national and international marrow banks, unrelated allogeneic
      BMT is being performed with increasing frequency. Graft-vs.-host disease (GVHD)
      remains a major complication of allogeneic BMT, occurring in 25% to 70% of
      patients despite GVHD prophylaxis, with the skin, gastro-intestinal tract, and
      liver as primary target organs. Oral findings are seen in both acute and chronic
      GVHD. In acute GVHD, the oral lesions are often painful, erythematous,
      ulcerative, and desquamative. In chronic GVHD, they are lichenoid with associated
      erythema and ulcerations; additionally, they may be associated with a sicca
      syndrome characterized by xerostomia and progressive salivary gland atrophy.
      General principles of BMT are discussed, as are systemic and local therapeutic
      options for oral GVHD.

PMID- 9167092
TI  - Streptococcal adhesion and colonization.
AB  - Streptococci express arrays of adhesins on their cell surfaces that facilitate
      adherence to substrates present in their natural environment within the mammalian
      host. A consequence of such promiscuous binding ability is that streptococcal
      cells may adhere simultaneously to a spectrum of substrates, including salivary
      glycoproteins, extracellular matrix and serum components, host cells, and other
      microbial cells. The multiplicity of streptococcal adherence interactions
      accounts, at least in part, for their success in colonizing the oral and
      epithelial surfaces of humans. Adhesion facilitates colonization and may be a
      precursor to tissue invasion and immune modulation, events that presage the
      development of disease. Many of the streptococcal adhesins and virulence-related
      factors are cell-wall-associated proteins containing repeated sequence blocks of
      amino acids. Linear sequences, both within the blocks and within non-repetitive
      regions of the proteins, have been implicated in substrate binding. Sequences and
      functions of these proteins among the streptococci have become assorted through
      gene duplication and horizontal transfer between bacterial populations. Several
      adhesins identified and characterized through in vitro binding assays have been
      analyzed for in vivo expression and function by means of animal models used for
      colonization and virulence. Information on the molecular structure of adhesins as
      related to their in vivo function will allow for the rational design of novel
      acellular vaccines, recombinant antibodies, and adhesion agonists for the future
      control or prevention of streptococcal colonization and streptococcal diseases.

PMID- 9167094
TI  - Factors affecting IL-1-mediated collagen metabolism by fibroblasts and the
      pathogenesis of periodontal disease: a review of the literature.
AB  - Fibroblasts have been studied extensively for their contribution to connective
      tissue destruction in diseases where the metabolism of extracellular matrix
      components plays an essential part in their pathogenesis. A considerable
      dissolution, especially of collagen fibrils, is a well-known characteristic of
      the periodontal ligament and the gingival connective tissue in microbial-induced
      periodontal disease. Fibroblasts, responsible for the assembly of the
      extracellular matrix, are capable of responding directly to oral microbial
      challenges or indirectly, following activation of the host immune response, and
      can alter the composition of connective tissue in several ways: synthesis of
      inflammatory mediators, their receptors and antagonists; fibroblast
      proliferation; collagen synthesis; phagocytosis of collagen fibrils; and
      synthesis of proteolytic enzymes, including matrix metalloproteinases and their
      corresponding inhibitors. The contributions of these cellular fibroblastic
      properties to the pathogenesis of periodontal disease are reviewed in the context
      of the cytokine, interleukin-1, as the inflammatory regulator.

PMID- 9167095
TI  - Medical management of sinusitis in pediatric patients.

PMID- 9167096
TI  - Streptococcus pneumoniae: impact of antibiotic resistance in pediatrics.

PMID- 9167097
TI  - Tales of medicine and poverty: child health in south Philadelphia, 1910 to 1930.

PMID- 9167098
TI  - Understanding error grid analysis.

PMID- 9167099
TI  - The independent and combined effects of aerobic exercise and dietary fish intake
      on serum lipids and glycemic control in NIDDM. A randomized controlled study.
AB  - OBJECTIVE: The triglyceride-lowering effects of omega-3 fats and HDL cholesterol
      raising effects of exercise may be appropriate management for dyslipidemia in
      NIDDM. However, fish oil may impair glycemic control in NIDDM. The present study
      examined the effects of moderate aerobic exercise and the incorporation of fish
      into a low-fat (30% total energy) diet on serum lipids and glycemic control in
      dyslipidemic NIDDM patients. RESEARCH DESIGN AND METHODS: In a controlled, 8-week
      intervention, 55 sedentary NIDDM subjects with serum triglycerides > 1.8 mmol/l
      and/or HDL cholesterol < 1.0 mmol/l were randomly assigned to a low-fat diet (30%
      daily energy intake) with or without one fish meal daily (3.6 g omega-3/day) and
      further randomized to a moderate (55-65% VO2max) or light (heart rate < 100 bpm)
      exercise program. An oral glucose tolerance test (75 g), fasting serum glucose,
      insulin, lipids, and GHb were measured before and after intervention. Self
      monitoring of blood glucose was performed throughout. RESULTS: In the 49 subjects
      who completed the study, moderate exercise improved aerobic fitness (VO2max) by
      12% (from 1.87 to 2.07 l/min, P = 0.0001). Fish consumption reduced triglycerides
      (0.80 mmol/l, P = 0.03) and HDL3 cholesterol (0.05 mmol/l, P = 0.02) and
      increased HDL2 cholesterol (0.06 mmol/l, P = 0.01). After adjustment for age,
      sex, and changes in body weight, fish diets were associated with increases in GHb
      (0.50%, P = 0.05) and self-monitored glucose (0.57 mmol/l, P = 0.0002), which
      were prevented by moderate exercise. CONCLUSIONS: A reduced fat diet
      incorporating one daily fish meal reduces serum triglycerides and increases HDL2
      cholesterol in dyslipidemic NIDDM patients. Associated deterioration in glycemic
      control can be prevented by a concomitant program of moderate exercise.

PMID- 9167100
TI  - Glucocorticoid-induced ketoacidosis in gestational diabetes: sequela of the acute
      treatment of preterm labor. A case report.
AB  - Pregnancy induces complex changes in energy metabolism, manifested clinically by
      insulin resistance, low fasting blood glucose levels, and proneness to ketosis.
      It is quite unusual for pregnant women who do not have type I diabetes to
      progress from ketosis to frank ketoacidosis, although this phenomenon is common
      in larger mammals. In the case described here, glucocorticoid administration in
      the setting of a prolonged fast triggered a metabolic cascade leading to
      ketoacidosis in a pregnant woman without type 1 diabetes. Other details of this
      illustrative case serve to synthesize several disparate observations regarding
      the pathogenesis of pregnancy ketoacidosis. Physicians should be aware of the
      potential for rapidly developing ketoacidosis with atypical biochemical and
      clinical features in pregnant women who are treated with high doses of
      glucocorticoids.

PMID- 9167101
TI  - Contraindications to metformin therapy in patients with NIDDM.
AB  - OBJECTIVE: Treatment with metformin is occasionally associated with the
      development of severe lactic acidosis. However, this is usually observed in
      patients with major contraindications to the drug. In this study, we aimed to
      determine the prevalence of conditions currently regarded as either
      contraindications or cautions to the use of metformin in patients with NIDDM.
      RESEARCH DESIGN AND METHODS: The case notes of metformin-treated NIDDM patients
      (mean age 62 years) attending a United Kingdom university hospital diabetes
      clinic over a 3-month period were reviewed according to criteria reflecting a
      pragmatic view of current prescribing recommendations. RESULTS: Of 89 consecutive
      patients whose notes could be evaluated in detail, only 41 (46%) had no
      contraindications or cautions to metformin whatsoever. Concomitant chronic
      disorders associated with a potentially increased risk of hyperlactatemia were
      renal impairment (n = 2; plasma creatinine concentrations 1.7 and 2.3 mg/dl,
      respectively), cardiac failure (n = 2), and chronic liver disease (n = 2). Other
      potentially relevant disorders included ischemic heart disease (n = 20), clinical
      proteinuria (n = 14), peripheral vascular disease (n = 22), and pulmonary disease
      (n = 7). Multiple conditions (i.e., two, three, or four) were present in eight,
      five, and one patient(s), respectively. CONCLUSIONS: More than half the patients
      in our series had concomitant conditions or complications conventionally regarded
      as cautions or contraindications to metformin; approximately 10% had a
      multiplicity of such conditions. Regular surveillance is necessary to detect the
      development of complications such as renal impairment. Vigilance is also required
      in view of the increased risk of major intercurrent illnesses, which may
      independently disturb lactate metabolism in patients with NIDDM. Metformin should
      be withdrawn promptly under such circumstances.

PMID- 9167102
TI  - Contribution of central neuropathy to postural instability in IDDM patients with
      peripheral neuropathy.
AB  - OBJECTIVE: To evaluate the contribution of central neuropathy on postural
      impairment observed in diabetic patients with peripheral neuropathy. RESEARCH
      DESIGN AND METHODS: Central sensory and motor nervous propagation, nerve
      conduction velocity, and static posturography were assessed in the following age
      matched subjects: 7 IDDM patients with peripheral neuropathy (group DN), 18 IDDM
      patients without peripheral neuropathy (group D), and 31 control subjects (group
      C). Somatosensory-evoked potentials (SEPs) during tibial nerve stimulation were
      recorded, and the spine-to-scalp sensory central conduction time (SCCT) was
      evaluated. Motor-evoked potentials (MEPs) were recorded from leg muscles during
      magnetic transcranial brain stimulation, and the scalp-to-spine motor central
      conduction time (MCCT) was evaluated. The following posturographic parameters
      were calculated from the statokinesigram: trace length, trace surface, velocity
      of body sway with its standard deviation, and VFY (a parameter derived from the
      velocity variance and the anteroposterior mean position of the body). RESULTS:
      SCCT was significantly higher in the DN group than in the C and D groups (P <
      0.001). MCCT was similar in all groups. Posturographic parameters were all
      significantly impaired in the DN group (P < 0.01). While posturographic
      parameters showed a direct relationship with some parameters of peripheral nerve
      conduction, no correlations were observed with SEP and MEP central conduction
      time. These results were also confirmed by logistic regression, which indicates
      peripheral neuropathy as the only implicating factor in postural instability
      (odds ratio 0.22, 95% CI 0.07-0.75) after data reduction by means of factor
      analysis. CONCLUSIONS: Although diabetic patients with peripheral neuropathy show
      a delay in central sensory conduction, postural instability may be fully
      explained by the presence of peripheral neuropathy.

PMID- 9167103
TI  - A prospective study of coronary heart disease in relation to fasting insulin,
      glucose, and diabetes. The Atherosclerosis Risk in Communities (ARIC) Study.
AB  - OBJECTIVE: To determine the association of coronary heart disease (CHD) incidence
      with diabetes, fasting serum glucose, and insulin in a biracial cohort of middle
      aged men and women. RESEARCH DESIGN AND METHODS: We examined a population-based
      sample (n = 13,446 free of baseline CHD) from four U.S. communities in 1987-1989.
      We defined diabetes on the basis of baseline fasting glucose concentration (> or
      = 7.8 mmol/l), medical history, and current medications. A central laboratory
      measured fasting insulin with a nonspecific radioimmunoassay. After 4-7 years,
      209 men and 96 women developed CHD. RESULTS: After adjustment for
      sociodemographic characteristics, smoking status, ethanol intake, sports
      participation, and hormone replacement therapy, the relative risk of CHD for
      people with diabetes versus those without diabetes was 3.45 (95% CI 2.16-5.50)
      among women and 2.52 (1.78-3.56) among men. Relative risks of CHD with diabetes
      were somewhat lower in blacks than non-blacks, but because diabetes was more than
      twice as prevalent in blacks, the percentage of CHD cases attributable to
      diabetes (population attributable risk) was 27% for black women, 15% for non
      black women, 8% for black men, and 12% for non-black men. Among people without
      diabetes, fasting glucose was not independently associated with CHD incidence.
      Among women without diabetes, there was a positive association between fasting
      insulin and CHD; multivariable adjusted relative risks of CHD across quintiles of
      fasting insulin were 1.00, 0.76, 2.08, 2.08 and 2.82 (P for linear trend = 0.02).
      However, among men without diabetes, fasting insulin and CHD were not associated.
      CONCLUSIONS: Diabetes conveys a high risk of CHD in black and non-black middle
      aged men and women. Fasting insulin, however, is a CHD risk factor only among
      women in this cohort.

PMID- 9167104
TI  - Gestational diabetes is a herald of NIDDM in Navajo women. High rate of abnormal
      glucose tolerance after GDM.
AB  - OBJECTIVE: To estimate the rate of deterioration of glucose tolerance and
      evaluate risk factors for development of NIDDM in Navajo women with a history of
      gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: A retrospective
      analysis of 111 GDM deliveries over a 4-year period, 1983-1987, was conducted in
      1994 to determine glucose tolerance status. Patients who had not developed NIDDM
      were recalled for a 2-h glucose tolerance test (GTT). Tested and non-tested
      patients were compared, as estimate of conversion to NIDDM was calculated, and
      risk factors for NIDDM were evaluated. A life-table analysis was developed to
      estimate the probability of NIDDM after GDM. RESULTS: At the time of chart
      review, 32 patients (29%) had already been diagnosed with NIDDM. Of the patients,
      79 were offered GTT testing, and 56 (71%) returned for follow-up; 15 were
      diagnosed with NIDDM and 17 with impaired glucose tolerance (IGT); 47 (42%) and
      64 (58%) patients in the cohort had developed NIDDM or NIDDM/IGT at the
      conclusion of the study period. Patients who developed NIDDM had greater BMIs,
      parity, and infant weights. Fasting blood glucose > 5.83 mmol/l, GTT > 41.63
      mmol/l, and recurrence of GDM were associated with later NIDDM. A life-table
      analysis estimated a 53% likelihood of having NIDDM at an 11-year follow-up; a
      second model, based only on patients with known NIDDM status, predicted a 70%
      rate of NIDDM at an 11-year follow-up. CONCLUSIONS: A high proportion of Navajo
      women with GDM progressed to NIDDM. Postpartum counseling and periodic GTTs are
      recommended.

PMID- 9167105
TI  - Health-related quality-of-life results from multinational clinical trials of
      insulin lispro. Assessing benefits of a new diabetes therapy.
AB  - OBJECTIVE: To compare health-related quality of life (HRQOL) in patients with
      diabetes receiving insulin lispro with patients receiving regular human insulin
      (Humulin R). RESEARCH DESIGN AND METHODS: We performed two randomized comparative
      studies over a 6-month period (3 months per treatment). Primary analyses used
      crossover baseline to 3-month changes in HRQOL scores. Ninety-three principal
      investigators in Canada, France, Germany, and the U.S. participated in these
      studies. One HRQOL crossover study included 468 patients with type I diabetes;
      the other HRQOL crossover study included 474 patients with type II diabetes. In
      both studies, patients were taking insulin at least 2 months before enrollment.
      Primary outcomes included two generic HRQOL domains, energy/fatigue and health
      distress, and two diabetes-specific domains, treatment satisfaction and treatment
      flexibility. Thirty secondary outcomes included both generic and diabetes
      specific measures. Secondary outcome domains were controlled for multiplicity in
      the analyses. RESULTS: Primary analyses showed that treatment satisfaction scores
      (P < 0.001) and treatment flexibility scores (P = 0.001) were higher for insulin
      lispro in type I diabetic patients. No other significant treatment differences
      were detected using the data from these 6-month crossover studies. CONCLUSIONS:
      Treatment satisfaction and treatment flexibility were significantly improved in
      patients with type I diabetes using insulin lispro. Other HRQOL findings were
      comparable for insulin lispro and regular human insulin. Insulin lispro appears
      to have a measurable impact on lifestyle benefits in patients with type I
      diabetes, as demonstrated by increased treatment satisfaction and treatment
      flexibility.

PMID- 9167106
TI  - A trial of cognitive analytic therapy in poorly controlled type I patients.
AB  - OBJECTIVE: This study compared the effect of cognitive analytic therapy (CAT), a
      focused time-limited psychotherapy, and diabetes specialist nurse education
      (DSNE) in a controlled trial of 26 chronically poorly controlled adult type I
      patients. RESEARCH DESIGN AND METHODS: Patients were randomized to either 16
      sessions of CAT (treatment) or 14-18 sessions of DSNE (control). Pre- and post
      treatment blood glucose control (HbA1), interpersonal difficulties, and diabetes
      knowledge were measured before and up to 9 months after treatment was completed.
      RESULTS: Although HbA1 levels improved in the DSNE group, at the end of treatment
      (mean fall 1.2%, P = 0.004) this was not maintained; so by the 9-month follow-up,
      the overall net fall was limited to 0.9% (P = 0.03 vs. entry value). There were
      no significant improvements in interpersonal difficulties in DSNE subjects at any
      retest point (P > 0.05). In contrast, glycemic control and interpersonal
      difficulties both improved after CAT. In contrast to DSNE, this improvement
      continued so that at the 9-month follow-up visit, the changes were significant
      (mean fall in HbA1 = 2%, P = 0.002 and P = 0.03 for the Inventory of
      Interpersonal Problems [IIP] scores). CONCLUSIONS: These results suggest that
      although there is no statistical difference between CAT and DSNE, the effects of
      CAT produce a more prolonged effect on glycemic control. If psychological
      difficulties underlying problems with self-care in a type I population are
      addressed, then improvements in diabetes control are likely to continue.

PMID- 9167107
TI  - Validity of screening for individuals at risk for type I diabetes by combined
      analysis of antibodies to recombinant proteins.
AB  - OBJECTIVE: To determine whether screening for the presence of multiple antibody
      markers for IDDM is effective at identifying individuals with high risk for
      disease development. RESEARCH DESIGN AND METHODS: Antibodies to GAD and the
      tyrosine phosphatase-like protein 1A-2 were determined in sequential serum
      samples from 44 first-degree relatives of IDDM patients, identified as possessing
      islet cell antibody (ICA) and/or insulin autoantibody (IAA), who were followed
      prospectively for IDDM development, ICA, IAA, and antibodies to GAD and 1A-2 were
      also determined in 93 cases of new-onset nonfamilial IDDM. RESULTS: The presence
      of two or more antibodies in addition to ICA or IAA conferred high risk (61%) for
      development of IDDM within 5 years of entry into the study and identified 89% of
      those who have developed IDDM on current follow-up. None of the relatives
      positive for ICA or IAA alone, in the absence of other antibody markers, have
      developed IDDM. Antibodies to islet antigens could both appear and disappear in
      follow-up samples obtained after entry into the study. The majority (60%) of
      young (< 16 years), sporadic cases of IDDM had multiple antibodies to islet
      antigens, but this proportion was lower in older patients (37%). CONCLUSIONS: A
      screening strategy based on the analysis of antibodies to multiple islet antigens
      can predict IDDM at high sensitivity and specificity in families, and such a
      strategy may also be applicable to identify young individuals in the general
      population with high disease risk. Since appearance of antibodies to different
      antigens occurs sequentially rather than simultaneously, accurate assessment of
      diabetes risk based on the presence of multiple antibodies will require follow-up
      over a number of years after the first evidence of islet autoimmunity.

PMID- 9167108
TI  - Comparison of laboratory test frequency and test results between African
      Americans and Caucasians with diabetes: opportunity for improvement. Findings
      from a large urban health maintenance organization.
AB  - OBJECTIVE: To compare African-American and Caucasian patients with preexisting
      diabetes in a health maintenance organization (HMO) on: 1) frequency with which
      they received a subset of recommended laboratory tests according to the American
      Diabetes Association (ADA) consensus guidelines and 2) the results of laboratory
      test values (glycosylated hemoglobin, cholesterol, and creatinine). RESEARCH
      DESIGN AND METHODS: A cross-sectional study of 2,312 HMO members with diabetes
      continuously enrolled during 1991 was conducted using computerized medical record
      and billing data. Receipt of the ADA recommended tests for glycosylated
      hemoglobin, cholesterol, and creatinine was compared between African-Americans
      and Caucasians, stratified by insulin requirements. In addition, group
      comparisons were made based on the laboratory test results. RESULTS: Less than 20
      percent of all subjects received the recommended number of ADA tests. This did
      not differ by race except for creatinine and cholesterol testing in insulin users
      only, where African-Americans had more tests. On average, after adjusting for
      covariates, African-Americans had significantly higher glycosylated hemoglobin
      and creatinine laboratory values. Both groups had elevated cholesterol values.
      CONCLUSIONS: The opportunity exists to improve the process of care for both
      African-Americans and Caucasians with diabetes in an HMO setting. The need to
      improve glycosylated hemoglobin results and subsequently limit complications is
      especially pressing among the African-American population.

PMID- 9167109
TI  - Relationship between weight change in young adulthood and the risk of NIDDM. The
      Sotetsu Study.
AB  - OBJECTIVE: To investigate the independent effect of weight change in young
      adulthood on the risk of prevalent NIDDM among middle-aged Japanese men. RESEARCH
      DESIGN AND METHODS: A case-control study was carried out in 895 male employees
      aged > or = 30 years of a railway company located in the vicinity of Tokyo.
      Adjusted odds ratios (ORs) were calculated for prevalent diabetes in each
      category of weight change (obtained from subjects' medical records) in young
      adulthood and adulthood. Adjustment for current age, initial BMI, and weight
      change in each age stratum was performed by the Mantel-Haenszel method or
      multiple logistic regression analysis. RESULTS: Weight change between 20 years of
      age and the age at maximum weight was not associated with the risk of NIDDM.
      Weight gain between 20 and 25 years of age was significantly and positively
      associated with the risk of NIDDM (OR 3.87 for gains > or = 10.0 kg, 2.53 for
      gains of 5.0-9.9%, and 3.73 for gains > or = 10.0%). On the other hand, moderate
      weight gain after 30 years of age was significantly inversely associated with
      NIDDM (OR 0.44 for gains of 5.0-9.9 kg, 0.15 for gains of 10.0-19.9%, and 0.38
      for gains of 20.0-29.9%). CONCLUSIONS: Extreme weight gain between 20 and 25
      years of age is a significant predictor of NIDDM, independent of current age, BMI
      at 20 years of age, and weight change within other age strata.

PMID- 9167110
TI  - IDDM incidence in a multiracial population. The Hawaii IDDM Registry, 1980-1990.
AB  - OBJECTIVE: The Hawaii IDDM Registry was created to determine the incidence rate
      of IDDM among children aged < 15 years of Oahu between 1980 and 1990. Because of
      the multiracial population living in Hawaii, it is an ideal state in which to
      study the effect of migration on IDDM incidence. RESEARCH DESIGN AND METHODS:
      Data were collected by a retrospective hospital chart review and physician
      survey. Registry criteria included 0-14 years of age at IDDM diagnosis and
      primary residence on Oahu. Children who were military dependents were excluded.
      Denominator data were compared from two sources. RESULTS: A total of 113 new
      onset IDDM cases were identified. Case ascertainment was 97%. The unadjusted
      annual incidence rate was 7.04-7.61 per 100,000 (95% CI 5.83-9.19), depending on
      which denominator source was used. Race- and ethnicity-specific rates varied
      greatly (all rates per 100,000): part Hawaiian, 15.34-16.58; Caucasian, 6.21
      6.71; Filipino, 3.66-3.96; and Japanese, 2.85-3.08. Temporally, the incidence
      fluctuated between a low of 2.96 per 100,000 in 1981 to highs of 11.11 and 11.85
      per 100,000 in 1985 and 1989, respectively. Ascertainment-corrected rates for
      these years (3.70, 11.76, and 13.48 per 100,000, respectively) show that the
      fourfold incidence increase between 1980 and 1989 was not due to ascertainment
      differences. CONCLUSIONS: IDDM incidence among children < 15 years of age in
      Hawaii was the lowest documented in the U.S. The incidence among part-Hawaiian
      children was 2.5 times greater than that of Caucasian children in Hawaii. IDDM
      incidence rates among Japanese children in Hawaii were comparable with rates in
      Japan. The temporal variation in IDDM incidence corresponded with a mid-1980s
      pandemic of IDDM documented elsewhere.

PMID- 9167111
TI  - Age and sex effects on HbA1c. A study in a healthy Chinese population.
AB  - OBJECTIVE: To evaluate whether glycohemoglobin levels increase with age in both
      sexes and to determine the effect of BMI on this increment. RESEARCH DESIGN AND
      METHODS: A cross-sectional survey of 4,580 healthy Chinese men and women, aged 20
      85 years, was performed. All subjects who did not have identifiable diseases and
      who were not on medication known to influence glucose tolerance were recruited
      from participants at the preventive services of the National Cheng-Kung
      University Hospital. As an indicator of plasma glucose levels, glycohemoglobin
      was measured. The subjects were classified according to their age and BMI for
      both men and women, and any relationships with glycohemoglobin levels were
      evaluated. RESULTS: In all the BMI groups divided into quartiles, glycohemoglobin
      levels increased with age. The largest elevation of glycohemoglobin was observed
      in the 45- to 54-year-old age-group, except in men with a BMI between the lowest
      and highest quartiles. The group with a BMI above the highest quartile had a
      higher glycohemoglobin than the group with a BMI below the lowest quartile in men
      aged < 54 years and women aged 35-64 years. Men had higher average
      glycohemoglobin levels than women < 55 years of age. CONCLUSIONS: The age factor
      itself may cause an elevation in glycohemoglobin independent of other age-related
      factors in Chinese men and women, and there is a sex difference with a lower
      average glycohemoglobin level in women before menopause. Furthermore, BMI, but
      not a family predisposition to diabetes or leisure-time physical activity,
      affects this age-dependent increase in glycohemoglobin levels.

PMID- 9167112
TI  - Glipizide-GITS does not increase the hypoglycemic effect of mild exercise during
      fasting in NIDDM.
AB  - OBJECTIVE: This study compared the effect of mild exercise while fasting on
      plasma glucose concentrations in subjects with NIDDM treated with extended
      release glipizide and subjects not taking an oral hypoglycemic agent. RESEARCH
      DESIGN AND METHODS: Twenty-five moderately obese subjects with NIDDM were
      randomized to treatment with extended-release glipizide or placebo. After 9 weeks
      of treatment, they fasted overnight, took their study drug, omitted breakfast,
      and exercised on a treadmill for 90 min. Glucose, insulin, and C-peptide
      concentrations were measured before, during, and after exercise. RESULTS: On the
      fasting-exercise day, fasting glucose concentrations were lower (153 vs. 241
      mg/dl, P < 0.01) and insulin and C-peptide concentrations higher in the extended
      release glipizide group. The decrement of glucose from the fasting baseline was
      modest and equivalent in the two groups: 17 vs. 21 mg/dl at the end of exercise
      and 28 vs. 27 mg/dl after 2 h of recovery. No subject had hypoglycemic symptoms.
      CONCLUSIONS: Chronic use of extended-release glipizide does not enhance the
      hypoglycemic effect of fasting plus mild exercise for people with NIDDM. Routine
      lifestyle treatments for NIDDM may be continued during ongoing use of this agent.

PMID- 9167113
TI  - Epalrestat, an aldose reductase inhibitor, improves an impaired generation of
      oxygen-derived free radicals by neutrophils from poorly controlled NIDDM
      patients.
AB  - OBJECTIVE: To study the in vivo effect of epalrestat (Epa), an aldose reductase
      inhibitor, on the generation of oxygen-derived free radicals by neutrophils from
      poorly controlled NIDDM patients (HbA1c > 10%). RESEARCH DESIGN AND METHODS: A
      total of 31 diabetic patients were randomly divided into two groups: an Epa(+)
      group of 16 patients treated with 150 mg/day epalrestat and an Epa(-) group of 15
      patients treated without epalrestat. A control group of 20 age- and sex-matched
      normal healthy subjects also participated. HbA1c, postprandial plasma glucose
      (PPG), and neutrophil bactericidal function were measured before and at the end
      of the drug treatment period (4 weeks). Neutrophil bactericidal function was
      measured as chemilu-minescence amplified by a Cypridina luciferin analog (CLA),
      which is dependent on O2- generation, and by luminol (L), which is highly
      dependent on OCl- generation, in response to formyl-methonyl-leucyl-phenylalanine
      (fMLP). RESULTS: At the start of the experiment, both CLA-dependent
      chemiluminescence (CLA-DCL) and L-dependent chemiluminescence (L-DCL) were
      clearly decreased in diabetic subjects (64 and 54%, respectively; P < 0.05)
      compared with control subjects (2,182 +/- 144 and 3,221 +/- 173 kc.min-1.10(-6)
      cells, respectively). At the end of the experiment, CLA-DCL and L-DCL in the
      Epa(+) group were significantly improved by 44 and 46%, respectively; however,
      these values were still lower than the corresponding results in the control
      group. HbA1c and PPG in both the Epa(+) and Epa (-) groups were significantly
      higher than in the control group, and treatment had no effect on either HbA1c or
      PPG. CONCLUSIONS: These data suggest that epalrestat may be a useful drug to
      prevent infection by improving the impaired O2- and OCl- generation by
      neutrophils from poorly controlled NIDDM patients.

PMID- 9167114
TI  - Determinants of progression of microalbuminuria in patients with NIDDM.A
      prospective study.
AB  - OBJECTIVE: To assess the degree of interindividual variation in the rate of
      progression of microalbuminuria and to identify determinants of progression of
      microalbuminuria in patients with NIDDM. RESEARCH DESIGN AND METHODS: In a
      prospective cohort study, 58 microalbuminuric NIDDM patients were followed for a
      period of at least 24 months. During this period, the level of microalbuminuria
      in these patients was assessed in triplicate 24-h urine samples on at least four
      separate visits. All patients had stable metabolic control and controlled blood
      pressure during follow-up. Microalbuminuria was defined as an albumin-to
      creatinine ratio in 24-h urine of between 3 and 30 mg/mmol. The individual rates
      of progression of microalbuminuria were calculated from linear regression
      analysis. At baseline, the following data were collected for all patients: age,
      sex, ethnicity, time since diagnosis of NIDDM, smoking habits, drug use, blood
      pressure, BMI, HbA1c, serum creatinine, cholesterol, triglyceride, and HDL
      cholesterol concentrations. RESULTS: Microalbuminuria was found to progress
      linearly in time. Considerable differences in rates of progression of
      microalbuminuria were found, the absolute yearly change in albumin-to-creatinine
      ratio ranging from -5.2 to 12.9 mg/mmol. In bivariate analyses, serum
      triglyceride concentration, use of ACE inhibitors, mean arterial blood pressure,
      HDL cholesterol, and time since diagnosis of NIDDM correlated with progression of
      microalbuminuria (P < or = 0.05). In stepwise multiple regression analysis, a
      high triglyceride-to-HDL cholesterol ratio at baseline (P = 0.006) and the use of
      ACE inhibitors (P = 0.007) were identified as the only independent predictors of
      progression of microalbuminuria. CONCLUSIONS: The rate of progression of
      microalbuminuria in NIDDM differs considerably between subjects. Diabetic
      dyslipidemia (high serum triglyceride and low HDL cholesterol) is a predictor of
      more rapid progression of microalbuminuria in patients with well-controlled blood
      pressure.

PMID- 9167115
TI  - Increased serum levels of advanced glycation end products (AGEs) in children and
      adolescents with IDDM.
AB  - OBJECTIVE: To investigate whether the serum levels of advanced glycation end
      products (AGEs) are increased in IDDM children and adolescents and to study the
      effect of puberty on serum levels of AGEs (S-AGEs). RESEARCH DESIGN AND METHODS:
      A total of 68 children and adolescent IDDM patients (age, 13.3 +/- 4.0 years;
      duration of diabetes, 5.0 +/- 3.6 years; HbA1c, 8.2 +/- 2.0%; Tanner stage
      [public hair], 1 vs. 2-5, 24/42) recruited from the pediatric outpatient clinic
      at Aker University Hospital were compared with 25 healthy nondiabetic control
      subjects. S-AGEs were measured by a fluoremetric immunoassay. RESULTS: S-AGEs
      were significantly elevated in the diabetic group when compared with the control
      group (14.4 +/- 3.5 vs. 11.7 +/- 3.0 U/ml, P < 0.002). A significant correlation
      (r = 0.26, P < 0.04) was found between S-AGEs and HbA1c in the diabetic group but
      not in the control group. No significant correlation was found between S-AGEs and
      the duration of diabetes in the diabetic group or S-AGEs and blood glucose
      concentration or age in either group. We found no difference between S-AGEs in
      boys and girls and in prepubertal and pubertal diabetic or control subjects.
      CONCLUSIONS: S-AGEs are increased in young patients with diabetes before puberty.
      Since AGEs are linked to the pathogenesis of vascular complications, this
      observation suggests that the pathological processes leading to diabetic late
      complications start even before puberty.

PMID- 9167116
TI  - Autoantibodies to sympathetic ganglia, GAD, or tyrosine phosphatase in long-term
      IDDM with and without ECG-based cardiac autonomic neuropathy.
AB  - OBJECTIVE: To evaluate the association of autoantibodies to complement-fixing
      sympathetic ganglia (CF-SG), and tyrosine phosphatase (IA-2) with
      electrocardiogram (ECG)-based cardiac autonomic neuropathy (CAN) in long-term
      IDDM. RESEARCH DESIGN AND METHODS: We examined the prevalence of autoantibodies
      to CF-SG (by complement-fixing indirect immunoflourescence), GAD, and IA-2 (by
      radioligand assay) and islet cells (by indirect immunofluorescence) in 96 long
      term IDDM patients (41 with ECG-based CAN, > or = 2 of 5 cardiac reflex tests
      abnormal; 55 without ECG-based CAN). As a control group, 89 healthy nondiabetic
      subjects were investigated. RESULTS: CF-SG autoantibodies were observed more
      frequently in long-term IDDM patients than in the control group (25 vs. 4%, P =
      0.0001). Of the IDDM patients, 14 (34%) with CAN and 10 (18%) without CAN
      presented with CF-SG autoantibodies (P = 0.06). GAD or IA-2 autoantibodies were
      detected in 14 (34%) and 17 (41%) IDDM patients with CAN, compared with 24 (44%)
      and 29 (53%) IDDM patients without CAN (P = 0.2, P = 0.2). Islet cell antibodies
      were observed in 6 (15%) IDDM patients with and in 9 (16%) IDDM patients without
      CAN (P = 0.5). CONCLUSIONS: In long-term IDDM, the role of CF-SG autoantibodies,
      which tend to be more frequent in patients with ECG-based CAN, requires further
      investigations. The persistence of GAD and IA-2 autoantibodies is not related to
      ECG-based CAN.

PMID- 9167117
TI  - Brain abnormalities demonstrated by magnetic resonance imaging in adult IDDM
      patients with and without a history of recurrent severe hypoglycemia.
AB  - OBJECTIVE: Previous studies of a cohort of 100 patients with IDDM have shown that
      a history of recurrent severe hypoglycemia is associated with a modest impairment
      of cognitive function. The aim of the present study was to determine whether IDDM
      patients with and without a history of severe hypoglycemia have lesions in the
      brain that are identifiable by magnetic resonance imaging (MRI) and magnetic
      resonance spectroscopy (MRS) and to investigate the putative relationship of any
      structural brain abnormalities with cognitive function. RESEARCH DESIGN AND
      METHODS: MRI and MRS of the brain were performed in 22 patients from the original
      cohort. Eleven IDDM patients with no history of severe hypoglycemia (group A)
      were compared with 11 IDDM patients who had a history of five or more episodes of
      severe hypoglycemia (group B). RESULTS: Nine patients (41%) had abnormal scans.
      Two types of abnormalities were observed: high-intensity rounded lesions, > 3 mm
      in diameters, distributed in the periventricular white matter (leukoaraiosis) in
      four patients; and cortical atrophy in five patients. Five patients in group B
      had cortical atrophy, whereas no patient in group A demonstrated this feature (P
      < 0.05). MRS of the frontal and parietal lobes showed no differences in the N
      acetyl aspartate/creatine or N-acetyl aspartate/choline ratios between groups A
      and B. Patients with cortical atrophy showed a nonsignificant trend toward
      reduced performance on Rapid Visual Information Processing. CONCLUSIONS: Brain
      abnormalities demonstrated by MRI are common in patients with IDDM of long
      duration and are suggestive of premature aging of the brain. IDDM per se may be
      an important pathogenic factor, but a significant association was observed
      between a history of recurrent severe hypoglycemia and cortical atrophy, which
      may be related to the modest impairment of cognitive function that has been
      reported previously.

PMID- 9167118
TI  - Transcapillary escape rate of albumin in type II diabetic patients. The
      relationship with microalbuminuria and hypertension.
AB  - OBJECTIVE: To study why in type II diabetes, microalbuminuria, a marker of
      generalized vascular dysfunction, and hypertension have been linked with both
      renal and cardiovascular organ damage. RESEARCH DESIGN AND METHODS: To
      investigate the effect of moderately elevated blood pressure on vascular damage,
      the transcapillary escape rate of albumin (TERalb) was measured by intravenous
      injection of purified 125I-human serum albumin in 9 healthy control subjects
      (group 1), 9 nondiabetic hypertensive subjects (group 2), and 73 nonobese type II
      diabetic patients stratified as follows: group 3: 17 normoalbuminuric
      normotensive subjects; group 4: 22 normoalbuminuric-hypertensive subjects
      (systolic blood pressure [sBP] > or = 140 mmHg or diastolic blood pressure [dBP]
      > or = mmHg or both); group 5: 16 normotensive subjects with microalbuminuria
      (albumin excretion rate [AER]: 20-200 micrograms/min); and group 6: 18
      microalbuminuric-hypertensive subjects. RESULTS: Groups 3-6 had similar age, sex,
      duration of diabetes (group 3: 7.8 +/- 5.5; group 4: 9.7 +/- 8.7; group 5: 12.1
      +/- 8.1; and group 6: 10.7 +/- 8.3 years), BMI, HbA1c (7.8 +/- 1.1, 7.5 +/- 1.5,
      8.7 +/- 1.5, and 7.7 +/- 1.1%, respectively), blood glucose, and lipid profile.
      Systolic and diastolic blood pressure did not differ in the three hypertensive
      group (group 2: 154 +/- 3/99 +/- 6; group 4: 149 +/- 13/95 +/- 6; group 6: 154 +/
      15/91 +/- 9 mmHg) and were significantly lower (P < 0.001) in group 3 (126 +/-
      12/76 +/- 7), group 5 (128 +/- 11/77 +/- 5), and healthy control subjects (group
      1: 133 +/- 7/81 +/- 4). TERalb was similar in control subjects (5.77 +/- 1.06%/h)
      and in normoalbuminuric-normotensive subjects (5.81 +/- 1.51%/h) but
      significantly higher (P < 0.0001) in microalbuminuric subjects with or without
      hypertension (9.11 +/- 1.65 and 8.60 +/- 1.50%/h, respectively) as well as in
      normoalbuminuric diabetic patients with hypertension (8.10 +/- 2.27%/h) and in
      essential hypertensive subjects (8.12 +/- 1.68%/h). CONCLUSIONS: By stepwise
      regression, TERalb was related (step 1) to log-AER (r = 0.30) or to the presence
      of microalbuminuria (r = 0.36) and (step 2) to dBP (multiple r = 0.40) or to the
      presence of hypertension (multiple r = 0.51) in the whole diabetic cohort (groups
      3-6). TERalb was related to dBP (r = 0.47) or to the presence of hypertension (r
      = 0.56) only in normoalbuminuric diabetic patients (groups 3 and 4) and to log
      AER (r = 0.56) or the presence of microalbuminuria (r = 0.68) only in
      normotensive patients (groups 3 and 5). In type II diabetic patients, TERalb was
      elevated in subjects with increased albuminuria, irrespective of blood pressure
      levels, but also was independently related to the presence of mild-to-moderate
      systemic hypertension.

PMID- 9167119
TI  - The limitations of clinical trials for prevention of IDDM.

PMID- 9167120
TI  - Reservations on the use of error grid analysis for the validation of blood
      glucose assays.

PMID- 9167122
TI  - Declaration of the Americas on Diabetes.

PMID- 9167121
TI  - The 32nd annual meeting of the European Association for the Study of Diabetes.
      Neuropathy, health care, and glycation.

PMID- 9167123
TI  - Influence of long-term glycemic control on the development of cardiac autonomic
      neuropathy in pediatric patients with type I diabetes.

PMID- 9167124
TI  - Prevalence of a polymorphism of the phosphatidylinositol 3-kinase p85 alpha
      regulatory subunit (codon 326 Met-->Ile) in Japanese NIDDM patients.

PMID- 9167125
TI  - Antibodies to GAD in chronic hepatitis C patients.

PMID- 9167126
TI  - The American Diabetes Association's Clinical Practice Recommendations and the
      developing world.

PMID- 9167127
TI  - Is hyperinsulinemia the cause of acanthosis nigricans in the type B syndrome of
      insulin resistance?

PMID- 9167128
TI  - Neonatal diabetes.

PMID- 9167129
TI  - Nutritional intake of Belgian diabetic children.

PMID- 9167130
TI  - Mixing insulin lispro and ultralente insulin.

PMID- 9167132
TI  - Changing pattern of diet in Europe.
AB  - The traditional wide range in diet in Europe that was based on climate and
      geography are slowly being eroded as modern transport and communications bring
      wider ranges of foods to the markets, and as modern travel cultures are eroding
      the boundaries of palatability. Tradition and history are still important
      factors, and the climatic variations are still there. Public education programmes
      encourage those living in the more northern countries to adopt a diet more
      similar to that consumed in the Mediterranean area. The programmes are having
      some success. Unfortunately, however, cultural factors seem to be persuading
      those living in the south to eat a more northern diet with more meat and animal
      fat.

PMID- 9167131
TI  - Vitamin nutritional status in Italy.
AB  - In almost all countries, the critical point for defining the nutritional status
      of a population is represented by the poor source of representative data of the
      whole population or of the main subgroups of the population. Also, in Italy, the
      sources of data on the nutritional status of biochemically evaluated macro- and
      micronutrients are scant in relation to specific groups of the population, mainly
      children and the elderly. In this short review, only the nutritional status for
      vitamins is considered. The existing limited data, however, indicate that
      clinical signs of severe deficiency are not observed in Italy and the incidence
      of vitamin malnutrition is moderate. This is probably due to the large
      availability and variety of food and to Italian eating habits which reflect the
      typical Mediterranean diet: rich, for example, in cereals, fresh fruit and
      vegetables, and olive oil. However, there are particular conditions, linked to
      lifestyle, in which the risk of a mild or moderate vitamin malnutrition
      increases. These include a monotonous diet, drug interactions, smoking habits and
      alcohol consumption.

PMID- 9167133
TI  - The antioxidant potential of the Mediterranean diet.
AB  - The Mediterranean diet not only produces favourable effects on blood lipids but
      also protects against oxidative stress. Oxidative damage is thought to represent
      one of the mechanisms leading to chronic diseases such as atherosclerosis and
      cancer. Many studies suggest that a link exists between fruit and vegetables in
      the diet or the amounts of plasma antioxidant vitamins (ascorbic acid, tocopherol
      and carotenoids) and risk of death from cancer or coronary heart diseases.
      Although a large emphasis has been given to different components of the diet,
      attention has recently shifted to the diet as a whole. The Mediterranean diet is
      able to modulate oxidative stress through complex mechanisms and not just the
      high antioxidant compound content. The preference for fresh fruit and vegetables
      in the Mediterranean diet will result in a higher consumption of raw foods, a
      lower production of cooking-related oxidants and a consequent decreased waste of
      nutritional and endogenous antioxidants. The high intake of antioxidant and fibre
      helps to scavenge even the small amount of oxidants or oxidized compounds.

PMID- 9167134
TI  - Effects of cooking and storage methods on the micronutrient content of foods.
AB  - Food processing has the potential to alter the nutrient quality of foods. This
      review deals with the effects of home-based cooking and storage practices on the
      micronutrient content of foods. It describes the effects of cooking, freezing and
      refrigeration on the vitamin and mineral content of meats, fish, fruit,
      vegetables and cereals. Based on this review, we suggest that the consumer should
      be aware of the possibility that losses in nutritional quality of foods may
      result from an improper use of cooking and storage techniques available at home.

PMID- 9167135
TI  - Free radicals, atherosclerosis, ageing and related dysmetabolic pathologies:
      biochemical and molecular aspects.
AB  - In human ageing and with many pathologies correlated to the senile functional
      decay of cells, membrane damage often occurs in some organ or tissue, which
      provokes lipid peroxidation in the membrane and accelerates the disorder in
      structure and function of the membrane. When lipid peroxides accumulate
      sufficiently, they leak from the organ or tissue into the bloodstream and
      increase the lipid peroxide level in blood lipoproteins. The increased lipid
      peroxides in the blood attack the blood vessel and promote atherogenesis. This
      paper describes the possible involvement of free radicals in this damage, both to
      tissues and to blood vessels, which contributes to the senile functional decay of
      the tissues.

PMID- 9167136
TI  - Free radicals, atherosclerosis, ageing, and related dysmetabolic pathologies:
      pathological and clinical aspects.
AB  - An excess of free-radical production has been linked to many diseases and to the
      ageing process. Oxidant by-products of normal metabolism can cause extensive
      damage to DNA, protein and lipid. Exposure to ultraviolet light, cigarette smoke
      and other environmental pollutants may also increase the free radical burden. The
      accumulation of unrepaired oxidative damage products is likely to be a major
      factor in cellular ageing. Many repair processes are available to the cell,
      including enzyme and structural defences. The large group of natural antioxidants
      is also part of a protective mechanism. High consumption of fruit and vegetables
      in the diet is associated with a lowered risk of degenerative diseases. At
      present, however, there are few data to support the routine use of exogenous
      antioxidants to prevent and treat these diseases.

PMID- 9167138
TI  - Intestinal flora and endogenous vitamin synthesis.
AB  - It is well established that the rumen microbial flora are a rich source of
      vitamins to the ruminant, and that the faecal bacterial flora are a major vitamin
      source for coprophagic rodents. There is also good evidence that the gut
      bacterial flora are a significant source of a range of vitamins to the human. In
      this paper evidence is presented that gut bacteria are a significant source of a
      range of vitamins, particularly those of the B group and vitamin K.

PMID- 9167137
TI  - High-risk subjects for vitamin deficiency.
AB  - Chronic deficiency of various vitamins can influence the occurrence of some
      chronic degenerative diseases such as cancer, cardiovascular pathology, cataract,
      arthritis, disorders of the nervous system and photosensitivity. Similarly,
      vitamin intake can influence various disorders in infants and elderly people, in
      burns and in subjects following unbalanced diets or undergoing strenuous physical
      exercise. Among vitamins, beta-carotene, vitamin E and vitamin C have received
      most attention, particularly in the prevention of oxidative damage from free
      radicals. It is supposed that each vitamin plays a different role in the
      pathogenesis of various diseases, depending on the type of damage relevant to a
      specific disease. Results from different studies are still far from conclusive
      and the effects on longevity are not well defined. In industrialized countries,
      vitamin deficiencies seem to be related only to specific and clearly identifiable
      groups in the population: therefore, at the moment, it seems more advisable to
      target vitamin supplementation at risk groups.

PMID- 9167139
TI  - Vitamins and cancer chemoprevention.
AB  - Chemoprevention is in an area of cancer research with perhaps the greatest
      potential for reducing cancer mortality. Several agents, and in particular
      antioxidant vitamins, appear to be effective against early rather than later
      steps of the premalignant process at different sites. Particular attention must
      be paid to possible side effects and safety of the agents and to optimal doses in
      long-term administration regimens. The results of numerous trials on the
      preventive role of vitamins (e.g. beta-carotene, retinols, retinoids, alpha
      tocopherol, ascorbic acid, folic acid) are contradictory and far from conclusive.
      Multiple primary and secondary intervention trials currently under way should
      assess in the coming years the role of some vitamins in the prevention of various
      cancers (oral cavity, pharynx, oesophagus, colon, lung, breast, skin, cervix,
      bladder).

PMID- 9167140
TI  - Exercise, free radical generation and vitamins.
AB  - Physical activity raises oxygen demand by many fold, causing a parallel increase
      in the formation of oxygen radical species. Vitamins are concerned with either
      energy metabolism or free radical scavenging. This review outlines the possible
      damage to cell structures following strenuous exercise and the role of vitamins
      as part of natural anti-oxidant defence systems. A brief discussion is included
      on the relationship between physical activity, the immune system and cancer.

PMID- 9167141
TI  - Trace elements and vitamins in immunomodulation in infancy and childhood.
AB  - It has been established that there is a strict and cyclical relationship between
      infection, immune function and nutritional status with changes in one influencing
      the other two. Impairment of immune function can occur even in healthy subjects
      in apparently good nutritional status as a consequence of some nutrient
      deficiencies. The impact of trace elements and vitamins on immune function are
      briefly reviewed.

PMID- 9167142
TI  - Vitamin requirements: present recommendations and future prospects.
AB  - Dietary recommendations evolved from instructions directed at prevention of
      starvation diseases to the level of intake of essential nutrients that are
      adequate to meet the known nutrient needs of practically all healthy persons.
      Vitamin requirements have been modified various times over the years and there
      are still differences in recommended intakes in different countries. A debate on
      optimal vitamin intake is ongoing, based on the concepts of deficiency,
      sufficiency and hypothetical identification of a range within which a further
      biological advantage can be expected. In establishing appropriate criteria for
      food and nutrient intakes, additional studies are warranted on the physiological
      interactions between nutrients and non-nutrients and on many other factors such
      as genetic determinants and lifestyle which could interfere with disease
      prevention.

PMID- 9167143
TI  - Surgical infection: current concerns.

PMID- 9167144
TI  - Pharmacotherapy--the facts and fantasies of prophylaxis and combined therapies.

PMID- 9167145
TI  - Local treatment of bone and soft tissue infections with the collagen-gentamicin
      sponge.

PMID- 9167146
TI  - Applications of local antibiotic therapy.

PMID- 9167147
TI  - Prevention of wound infection in elective colorectal surgery by local application
      of a gentamicin-containing collagen sponge.
AB  - Preoperative antibiotic prophylaxis is known to significantly reduce the
      incidence of postoperative wound infection in elective colorectal surgery, and is
      a recognized part of surgical management. Antibiotics are usually given
      systemically or orally, or by a combination of the two routes. Local antibiotic
      delivery to the wound site using an implanted, reabsorbable, gentamicin
      containing collagen sponge is a novel concept. We compared postoperative wound
      infection rates in 221 colorectal surgery patients randomized to receive systemic
      gentamicin/metronidazole with (Group I, n = 107) or without (Group II, n = 114)
      the gentamicin-collagen sponge. The two patient groups were identical on the
      basis of demographics and operations undergone. The postoperative wound infection
      rate was significantly lower in Group I patients than Group II 5.6% (6/107) and
      18.4% (21/ 114), respectively (p < 0.01). The mean duration of hospital stay was
      13.8 days in Group I and 16.3 days in Group II, which did not represent a
      statistically significant difference. The gentamicin collagen sponge was well
      tolerated and no adverse events were reported that were attributable to its use.
      This new method for delivering gentamicin directly to the operative site may
      represent a significant method for reducing postoperative wound infection rates
      to levels lower than those currently achieved with systemic antibiotics alone.

PMID- 9167149
TI  - Intra-aortic balloon perforations.

PMID- 9167148
TI  - Intra-aortic balloon pumps.
AB  - Intra-aortic balloon pumps (IABPs) are circulatory assist devices used to treat a
      number of cardiovascular conditions. IABPs provide temporary circulatory support
      by reducing the resistance to blood flow out of the heart during systole and by
      providing added pressure to aid in perfusing the heart during diastole. In this
      Evaluation, we tested three IABPs from three suppliers. We examined the units'
      technical performance, safety and monitoring, human factors design, transport
      operation, and supplier support. Rather than test all the triggering (activation)
      modes available, we focused our testing on the modes most commonly used on each
      unit. We also provide information on an IABP currently available only in Japan;
      although we did not test this unit, we do provide a preliminary judgment based on
      the information provided to us by the supplier. In the Technology Overview also
      included in the Evaluation, we describe the basic operation and use of an IABP,
      as well as review the state of the art of this technology. And in the Selection,
      Purchasing, and Use Guide at the conclusion of the Evaluation, we discuss such
      topics as balloon costs and sizing, interfacing IABPs with patient monitors, and
      the use of IABPs in community hospitals.

PMID- 9167150
TI  - Blood residue in Datascope System 97 IABP can cause malfunction.

PMID- 9167151
TI  - Frequent system error message disables McGaw Horizon Modular System Model 600
      infusion pumps.

PMID- 9167152
TI  - IMED/IVAC IMED Gemini series general-purpose infusion pumps disabled by corrosion
      in protective circuit.

PMID- 9167154
TI  - Feasibility of a large area x-ray sensitive vidicon for medical fluoroscopy:
      resolution and lag factors.
AB  - A large area x-ray-sensitive vidicon utilizing amorphous selenium (a-Se) is being
      investigated as an alternative to the x-ray image intensifier and television
      camera combination (XRII/TV) for medical fluoroscopy. The x-ray vidicon is, to a
      first approximation, a scaled up version of the 1" (2.54 cm) light-sensitive
      vidicon. The modulation transfer function (MTF) of an x-ray vidicon is mainly
      determined by the number of lines used, the beam spot profile, and the electronic
      bandwidth. The x-ray vidicon is expected to have roughly the same MTF as the 1"
      vidicon from a XRII/TV system referenced to the x-ray input and as such will be
      superior to the MTF of the complete XRII/TV system especially in high resolution
      applications such as cardiac cine. Beam discharge lag is expected to be
      approximately the same as in the 1" vidicon since they have comparable
      photoconductor layer capacitance. Photoconductive lag is also expected to be low
      since a-Se is known to have a low trap density.

PMID- 9167153
TI  - Feasibility of a large area x-ray sensitive vidicon for medical fluoroscopy:
      signal and noise factors.
AB  - A large area x-ray sensitive vidicon is being investigated as an alternative to
      the x-ray image intensifier and television camera combination for medical
      fluoroscopy. Signal generation in an x-ray vidicon involves an x-ray
      photoconductive layer whose surface is scanned by an electron beam. The single x
      ray to electron conversion stage of the x-ray vidicon offers a greatly improved
      modulation transfer function (MTF) over the x-ray image intensifier. This
      superior MTF allows signal and x-ray quantum noise at high spatial frequencies to
      be passed to the preamplifier with less attenuation. In cardiac cine applications
      this would allow quantum noise limited operation at higher spatial frequencies
      than is possible with the x-ray image intensifier system.

PMID- 9167155
TI  - Improved determination of biplane imaging geometry from two projection images and
      its application to three-dimensional reconstruction of coronary arterial trees.
AB  - A technique has been developed for accurate estimation of three-dimensional (3D)
      biplane imaging geometry and reconstruction of 3D objects based on two
      perspective projections acquired at arbitrary orientations, without the need of
      calibration. The required prior information (i.e., the intrinsic parameters of
      each single-plane imaging system) for determination of biplane imaging geometry
      includes (a) the distance between each focal spot and its image plane, SID (the
      focal-spot to imaging-plane distance); (b) the pixel size, psize (e.g., 0.3
      mm/pixel); (c) the distance between the two focal spots ff' or the known 3D
      distance between two points in the projection images; and (d) for each view, an
      approximation of the magnification factor, MF (e.g., 1.2), which is the ratio of
      the SID and the approximate distance of the object to the focal spot. Item (d) is
      optional but may provide a more accurate estimation if it is available. Given
      five or more corresponding object points in both views, a constrained nonlinear
      optimization algorithm is applied to obtain an optimal estimate of the biplane
      imaging geometry in the form of a rotation matrix R and a translation vector t
      that characterize the position and orientation of one imaging system relative to
      the other. With the calculated biplane imaging geometry, 3D spatial information
      concerning the object can then be reconstructed. The accuracy of this method was
      evaluated by using a computer-simulated coronary arterial tree and a cube phantom
      object. Our simulation study showed that a computer-simulated coronary tree can
      be reconstructed from two views with less than 2 and 8.4 mm root-mean-square
      (rms) configuration (or relative-position) error and absolute-position error,
      respectively, even if the input errors in the corresponding 2D points are fairly
      large (more than two pixels = 0.6 mm). In contrast, input image error of more
      than one pixel (= 0.3 mm) can yield 3D position errors of 10 cm or more when
      other existing methods based on linear approaches are employed. For the cube
      phantom images acquired from a routine biplane system, rms errors in the 3D
      configuration of the cube and the 3D absolute position were 0.6-0.9 mm and 3.9
      5.0 mm, respectively.

PMID- 9167156
TI  - Efficiency of low-contrast detail detectability in fluoroscopic imaging.
AB  - The detectability of a static low-contrast detail in the dynamic fluoroscopic
      image of a homogeneous phantom was assessed by physical measurement of the signal
      to-noise ratio (SNR) and by psychophysical measurement of the human observer
      detectability index d'. The two-alternative forced-choice method was used for
      human observer tests. The image data consisted of digitally recorded fluoroscopic
      image sequences which were displayed in a continuous loop of varying length (1-50
      frames) at a rate of 25 frames/s. Human detection performance was seen to improve
      with the SNR in all cases studied: when the signal was made stronger, the image
      noise lower, or when the SNR in the image sequence was made higher by increasing
      the length of the image sequence. The results imply that the statistical
      efficiency of humans decreases slowly when the number of frames in the displayed
      loop is increased. This decrease of efficiency with loop length was not seen in
      all test series, however, and it is possible that the phenomenon is partly
      related to the high d' values found at the greatest loop lengths studied. When
      the display contrast was high, the statistical efficiency of the human observer
      was 30%-40% for both static and dynamic images. The efficiency was somewhat
      lower, 15%-25%, for images that were displayed with a display contrast gain
      setting more typical of fluoroscopy. The accumulation rate of SNR2 is a suitable
      quantity for the measurement of fluoroscopic image quality as related to a given
      static signal detection task. In contrast to this, visibility measurement by
      determination of the threshold contrast was seen to be unacceptably imprecise if
      the test is based on only one observer's opinion, as is often the case in
      practical quality assurance testing. The precision of the threshold contrast
      measurement could, however, be improved by using several observers and test
      objects with a smaller step between details than is usual.

PMID- 9167157
TI  - Analysis of the temporal response of computed tomography fluoroscopy.
AB  - Computed tomography fluoroscopy (CTF) has found many applications in
      interventional procedures. The advantage of CTF is its ability to remove
      overlapping structures in the human anatomy and, thereby, provide accurate
      spatial information. Another advantage is its ability to reconstruct images in a
      short period of time so that "real-time" information can be provided. In this
      paper, we perform theoretical analysis and computer simulations to evaluate the
      temporal response of the CTF. We investigate the impact of various reconstruction
      algorithms on CTF and demonstrate the inherent limitations of the CTF in terms of
      the time lag and delay. The analysis provides a useful guidance to the CTF
      operators to avoid potential pitfalls.

PMID- 9167158
TI  - Velocity measurement based on bolus tracking with the aid of three-dimensional
      reconstruction from digital subtraction angiography.
AB  - The problem of blood flow measurement in x-ray angiography using measurements of
      the leading edge of the contrast bolus as it traverses the vascular bed is
      considered. A new technique for velocity measurement is presented based upon the
      ratio of the temporal derivative to the spatial derivative of the contrast bolus
      in the direction of flow. With the addition of a small correction factor, the
      value obtained is shown to reflect the transport velocity, or the velocity at
      which the contrast is transported down the vessel of interest. Most blood flow
      measurements based on bolus tracking techniques are actually using the contrast
      transport velocity to represent the blood flow velocity. Because of the streaming
      that occurs due to laminary flow conditions, the measured transport velocity is
      found to be somewhere between the average and the peak (central) fluid velocities
      for measurements taken during the traversal of the bolus leading edge. The
      spatial and temporal variation of the transport velocity are found to be
      consistent with the bolus motion expected in the presence of laminar flow. From x
      ray images of contrast passage through simple tubes, we find that the derivative
      method measures the transport velocity during passage of the bolus leading edge.
      In most cases of laminar blood flow, the leading edge transport velocity can be
      20%-40% higher than the average blood velocity.

PMID- 9167159
TI  - A real vessel phantom for imaging experimentation.
AB  - Vascular phantoms are used to evaluate imaging techniques such as ultrasound
      (US), CT, and angiography. They are expected to mimic the vasculature,
      surrounding tissue, and blood, and therefore must meet specific requirements on
      the mimicking materials, with respect to x-ray attenuation and acoustic
      properties (velocity, attenuation). In the past, researchers have used a variety
      of vessel models, including walled (typically latex tube) and wall-less phantoms
      (obtained by moulding a lumen in a block of agar). These models lacked the exact
      geometry of human vessels as well as pathologic features such as plaques and
      calcifications. To overcome these disadvantages, this paper describes a real
      vessel phantom for US and x-ray studies. The phantom consists of an agar-filled
      acrylic box containing a formaldehyde fixed section of a real human vessel
      (obtained at autopsy) cannulated onto two acrylic tubes. This phantom was
      evaluated by comparing the images obtained with x-ray angiography, CT, and 3-D B
      mode US. The images show good overall correlation based on the location of the
      geometrical features within the phantom, such as lumen, plaques, and
      calcifications. Discrepancies, artifacts, and difficulties were minor, and are
      discussed. The use of a real vessel, with its natural geometry and pathology,
      makes this phantom attractive for evaluation of imaging techniques including
      projection radiography, CT and US, and for extending its use to MR and US based
      flow studies.

PMID- 9167160
TI  - Estimation of a photon energy spectrum for a computed tomography scanner.
AB  - Estimated photon energy spectra are derived from transmission measurements using
      aluminium, copper, and sodium iodide absorbers. Two spectral models are proposed.
      One is based on a previously published model that analyzes the electron's
      penetration into the anode, and the production and attenuation of bremsstrahlung
      photons. The second model does not include details regarding the underlying
      physics, but treats the spectrum as a sum of delta functions. A nonlinear
      regularization method is used to overcome ill conditioning in the second model.
      Both models fit the transmission data to an accuracy of 0.30%, which is
      consistent with the experimental error. A quantitative comparison of the models
      is made by calculating the average and variance (over the derived energy spectra)
      of several relevant mass attenuation coefficients. The maximum variation in the
      average and variance was 1.5% and 3.2%, respectively, indicating that the spectra
      exhibit similar attenuation and beam hardening properties. The spectra were
      tested with a simulation that predicts scanner CT numbers for phantom
      measurements consisting of dilutions of sodium iodide in a water equivalent
      background. The agreement between simulation and experiment ranged from 1.5% at
      220 HU to 4.4% at 1700 HU.

PMID- 9167161
TI  - Primary beam exposure outside the fluoroscopic field of view.
AB  - Fluoroscopic units can irradiate an area outside the displayed field of view
      (FOV) which provides no additional information to the fluoroscopist and may
      significantly increase the integral dose to the patient. This unnecessary
      exposure can be reduced using region of interest (ROI) filtration techniques to
      attenuate the x rays peripheral to the ROI as well as outside the displayed FOV
      [Granger et al., Med. Phys. 23, 1059 (1996)]. A survey was conducted to
      quantitatively determine the deviation between the total exposed area and the
      displayed FOV on 18 fluoroscopic x-ray units which have different shaped
      collimation. A film was taken in fluoroscopic mode and the area of the FOV was
      determined from the image of markers placed at the edge of the displayed FOV. For
      each unit, a measurement was made for each magnification mode at various source
      to image distances. The measured difference between the total exposed area and
      the area of the displayed FOV ranged between 5% and 32% for units meeting federal
      compliance standards and between 22% and 48% for units which were found to be out
      of compliance. The results of the survey and the application of ROI imaging
      techniques as a possible method to reduce dose due to inexact fluoroscopic
      collimation are presented.

PMID- 9167162
TI  - Automated analysis of the American College of Radiology mammographic
      accreditation phantom images.
AB  - A significant metric in federal mammography quality standards is the phantom
      image quality assessment. The present work seeks to demonstrate that automated
      image analyses for American College of Radiology (ACR) mammographic accreditation
      phantom (MAP) images may be performed by a computer with objectivity, once a
      human acceptance level has been established. Twelve MAP images were generated
      with different x-ray techniques and digitized. Nineteen medical physicists in
      diagnostic roles (five of which were specially trained in mammography) viewed the
      original film images under similar conditions and provided individual scores for
      each test object (fibrils, microcalcifications, and nodules). Fourier domain
      template matching, used for low-level processing, combined with derivative
      filters, for intermediate-level processing, provided translation and rotation
      independent localization of the test objects in the MAP images. The visibility
      classification decision was modeled by a Bayesian classifer using threshold
      contrast. The 50% visibility contrast threshold established by the trained
      observers' responses were: fibrils 1.010, microcalcifications 1.156, and nodules
      1.016. Using these values as an estimate of human observer performance and given
      the automated localization of test objects, six images were graded with the
      computer algorithm. In all but one instance, the algorithm scored the images the
      same as the diagnostic physicists. In the case where it did not, the margin of
      disagreement was 10% due to the fact that the human scoring did not allow for
      half-visible fibrils (agreement occurred for the other test objects). The
      implication from this is that an operator-independent, machine-based scoring of
      MAP images is feasible and could be used as a tool to help eliminate the effect
      of observer variability within the current system, given proper, consistent
      digitization is performed.

PMID- 9167163
TI  - Laser-based microfocused x-ray source for mammography: feasibility study.
AB  - A laser-produced plasma (LPP) x-ray source with possible application in
      mammography was created by focusing a laser beam on a Mo target. A Table-Top
      Terawatt (TTT) laser operating at 1 J energy per pulse was employed. A dual pulse
      technique was used. Maximum energy transfer (approximately 10%) from laser light
      to hot electrons was reached at a 150 ps delay between pulses and the conversion
      efficiency (hard x-ray yield/laser energy input) was approximately 2 x 10(-4).
      The created LPP x-ray source is characterized by a very small focal spot size
      (tens of microns), Gaussian brightness distribution, and a very short pulse
      duration (a few ps). The spectral distribution of the generated x rays was
      measured. Images of the focal spot, using a pinhole camera, and images of a
      resolution pattern and a mammographic phantom were obtained. The LPP focal spot
      modulation transfer function for different magnification factors was calculated.
      We have shown that the LPP source in conjunction with a spherically bent, high
      throughput, crystal monochromator in a fixed-exit Rowland circle configuration
      can be used to created a narrow band tunable mammography system. Tunability to a
      specific patient breast tissue thickness and density would allow one to
      significantly improve contrast and resolution (exceeding 20 lp/mm) while lowering
      the exposure up to 50% for thicker breasts. The prospects for the LPP x-ray
      source for mammographic application are discussed.

PMID- 9167164
TI  - A bandwidth indicator for magnetic resonance imagers.
AB  - Signal-to-noise ratios in magnetic resonance imaging are crucial in determining
      image quality, and dependent on a number of factors, one being the signal
      bandwidth per pixel. Not all manufacturers clearly state the bandwidth per pixel
      used for all sequences. A small battery-powered portable device is described
      which produces bright sharp lines on the magnetic resonance image at 10 kHz
      intervals in the frequency encoding direction. The bandwidth per pixel can then
      easily be calculated using electronic distance callipers, provided the image
      matrix and field of view are known. The device is expected to be especially of
      value when acceptance testing on poorly documented imaging systems.

PMID- 9167165
TI  - A three-dimensional volumetric test object for geometry evaluation in magnetic
      resonance imaging.
AB  - The design of a test object for the volumetric evaluation of geometric image
      quality parameters in magnetic resonance imaging (MRI) is presented. Two
      dimensional parameters: linearity, distortion, slice position, slice width, slice
      oblique angle, spatial resolution, line spread function (LSF) are measurable in
      all slice planes within a volume corresponding to a typical head examination.
      Additionally, parameters particular to three-dimensional Fourier transform (3
      DFT) imaging are measurable: 3D ghosting and 3D LSF. Parameter measurements are
      correctable with regard to test object positioning through the determination of
      the six degrees of freedom of the test object within the scanner's field of view.

PMID- 9167166
TI  - Refinements of the finite-size pencil beam model of three-dimensional photon dose
      calculation.
AB  - Modern three-dimensional (3-D) photon dose calculation algorithms need to be fast
      and accurate if they are to be practical for treatment optimization. Refinements
      to a previously proposed finite-size pencil beam (FSPB) method are presented in
      order to fulfill these needs. Specifically, a fast Fourier transform (FFT)
      convolution technique is used to speed calculation of the FSPB; the fluence
      spectrum is modeled, and the effects of finite source size, a Gaussian x-ray
      source intensity profile and partial transmission through a multileaf collimator
      (MLC) leaf are approximated. The use of FFT techniques in the calculation of
      small diverging fields involves approximations that are investigated for a 6 MV
      beam and shown to introduce errors that vary with energy but do not exceed 0.7%
      on the central axis. Dose distributions calculated by FSPB superposition are in
      excellent agreement with those calculated by full field FFT convolution. Two key
      advances over the original implementation of the FSPB model are demonstrated: the
      fast calculation of the FSPB facilitates development, and the incorporation of
      realistic beam parameters enables accurate modeling of clinical beams.

PMID- 9167167
TI  - Anisotropy of an 192iridium high dose rate source measured with a miniature
      ionization chamber.
AB  - The anisotropy of a high dose rate (HDR) 192Ir source was measured in air and in
      water using a miniature (0.147 cm3) ionization chamber. Measurements were made at
      a distance of 5 cm from the source center at polar angles from 10 degrees-170
      degrees. The anisotropy was found to be less pronounced in water, and the
      anisotropy is asymmetric about the transverse axis. The results agree with
      previous ionization chamber and TLD measurements to within +/- 4%. Mean
      anisotropy factors were determined at each angle from all existing data at 5 cm
      distance, and compared to published Monte Carlo calculations, and to the values
      used in the microSelectron HDR brachytherapy planning system (BPS). The Monte
      Carlo photon transport code appears to systematically underestimate the
      anisotropy factor by up to 4% in the forward direction and overestimate it by up
      to 3% in the backward direction. The mean anisotropy factors also indicate that
      the BPS systematically underestimates the anisotropy factor by up to 3% in the
      forward direction, and overestimates it by up to 15% in the backward direction.
      However, the 15% difference occurs at 180 degrees where it is not likely to be
      clinically significant.

PMID- 9167168
TI  - Geometric analysis of light-field position of a multileaf collimator with curved
      ends.
AB  - The purpose of this work was to analyze the difference between the light-field
      edge and the radiation field edge produced by multileaf collimator (MLC) leaves
      that are constructed with rounded ends. A formula was derived using three
      dimensional geometry predicting the location of the ideal point-source light
      field edge relative to the geometric projection of the tip of the rounded leaf
      end. The theoretical edge of the radiation field for a point source was also
      calculated along the projection of a chord whose length was one Half-Value
      Thickness (HVT). Analytic solutions were found for the radiation-field edge and
      the transmission penumbra. The displacement of the light-field edge relative to
      the projection of the leaf tip varied from 0 mm for the leaf tip projected onto
      the central axis to approximately 3.2 mm for the leaf tip projected to 20 cm off
      the central axis. The light-field edge was always displaced into the unblocked
      area. The location of the projection of the 1 HVT chord was displaced from the
      light-field edge by a small and essentially constant distance (approximately 0.3
      mm) for all field sizes. The transmission penumbra (80%-20%) was about 1.2 mm for
      all leaf positions. The calibration of the leaf position must account for the
      nonlinear relationship between the leaf-tip projection and the light-field (or
      radiation-field) edge.

PMID- 9167169
TI  - Off-axis primary-dose measurements using a mini-phantom.
AB  - The characterization of the incident photon beam is usually divided into its
      dependence on collimator setting (head-scatter factor) and off-axis position
      (primary off-axis ratio). These parameters are normally measured "in air" with a
      build-up cap thick enough to generate full dose build-up at the depth of dose
      maximum. In order to prevent any influence from contaminating electrons, it has
      been recommended that head-scatter measurements are carried out using a mini
      phantom rather than a conventional build-up cap. Due to the volume of the mini
      phantom, the effects from attenuation and scatter are not negligible. In relative
      head-scatter measurements these effects cancel and the head scatter is thus a
      good representation of the variation of the incident photon beam with collimator
      setting. However, in off-axis measurements, attenuation and scatter conditions
      vary due to beam softening and do not cancel in the calculation of the primary
      off-axis ratio. The purpose of the present work was to estimate the effects from
      attenuation and phantom scatter in order to determine their influence on primary
      off-axis ratio measurements. We have characterized the off-axis beam-softening
      effect by means of narrow-beam transmission measurements to obtain the effective
      attenuation coefficient as a function of off-axis position. We then used a semi
      analytical expression for the phantom-scatter calculation that depends solely on
      this attenuation coefficient. The derived formalism for relative "in air"
      measurements using a mini-phantom is clear and consistent, which enables the user
      to separately calculate the effects from scatter and attenuation. For the
      investigated beam qualities, 6 and 18 MV, our results indicate that the effects
      from attenuation and scatter in the mini-phantom nearly cancel (the combined
      effect is less than 1%) within 12.5 cm from the central beam axis. Thus, no
      correction is needed when the primary off-axis ratio is measured with a mini
      phantom.

PMID- 9167170
TI  - Validation of reconstructed bremsstrahlung spectra between 6 MV and 25 MV from
      measured transmission data.
AB  - We have previously investigated a method of high-energy x-ray spectral
      reconstruction from transmission data by direct resolution of a matrix system.
      This technique uses the spectral vectorial algebra formalism. The resolution has
      previously been tested on a 12 MV photon beam. To extend and to test the validity
      of the results to the entire radiotherapy energy range, we have performed the
      method on photon beams with nominal energies of 6, 12, 15, and 25 MV. The
      influence on the 6 MV spectrum of a 60 degrees built-in wedge has also been
      investigated to test the sensitivity of the method and the results are reported.
      To validate our reconstructed spectra, dosimetric quantities such as tissue
      phantom ratios (TPR), water-to-air stopping power ratios (S/p) air water, and
      quality indexes TPR 10 (20) have been calculated. The results show good agreement
      between the measured and calculated data. Mean mass energy absorption coefficient
      ratios for different materials have also been computed and compared to data
      published recently and the results are very close (within +/- 0.5%). Primary
      depth dose functions in water have also been computed to deduce primary dose
      attenuation coefficients.

PMID- 9167171
TI  - A new approach to film dosimetry for high energy photon beams: lateral scatter
      filtering.
AB  - A method of film dosimetry for high energy photon beams is proposed which reduces
      the required film calibration exposures to a set of films obtained for a small
      radiation field size and shallow depth (6 cm x 6 cm at 5 cm depth). It involves
      modification of a compression type polystyrene film phantom to include thin lead
      foils parallel to the vertical film plane at approximately 1 cm from both sides
      of the film emulsion. The foils act as high atomic number filters which remove
      low energy Compton scatter photons that otherwise would cause the film
      sensitivity to change with field size and depth. The proposed method is best
      described as "lateral scatter filtering." To validate the proposed method,
      central axis depth doses and isodose curves for a 4 MV photon beam were
      determined from films exposed within the modified phantom and the results
      compared with ionization chamber measurements. When no lateral filtering was
      used, for field sizes of 6 cm x 6 cm and 25 cm x 25 cm, this comparison
      demonstrated up to a 65% difference between film and ionization chamber central
      axis depth dose measurements. When using the lateral scatter filtering technique,
      less than a 4% difference was observed for these field sizes.

PMID- 9167172
TI  - Energy-dependent polarity correction factors for four commercial ionization
      chambers used in electron dosimetry.
AB  - The polarity effects of four commercially available ionization chambers were
      characterized and correction factors as a function of mean energy at depth were
      tabulated. These included a Farmer-type chamber, two parallel plate chambers, and
      one cylindrical chamber used in a scanning water phantom dosimetry system.
      Polarity effects were measured at representative depths along the depth dose
      curves of 6, 9, 12, 16, and 20 Me V electron beams. The term "polarity error" is
      introduced and is defined as the error which is introduced if polarity effects
      are ignored. Polarity errors for the four ionization chambers studied were shown
      to monotonically decrease with increasing mean energy at depth and were largely
      independent of the energy of the incident electron beam. Only at very low
      energies, that is, very near the end of the practical range, did the correction
      factors for beams of different incident energy diverge. Three of the four
      chambers studied had correction factors which were independent of field size, to
      within +/- 1/2%. One chamber showed an increase in correction factor with
      increasing field size which was shown to be mainly due to stem and cable
      irradiation.

PMID- 9167173
TI  - Melanosomal proteins as melanoma-specific immune targets.
AB  - Pigmentation of our skin, hair and eyes is essential for photoprotection,
      embryological development, detoxification and protective/cosmetic coloration. A
      number of proteins important to the production of melanin within melanosomes have
      now been identified including enzymatic and structural proteins encoded at the
      murine albino, brown, pinkeyed-dilution, MART1, slaty and silver loci.
      Interestingly, many of those melanosomal proteins (including epitopes derived
      from tyrosinase, TRP1/gp75, silver/gp100 and MART1/melan-A) function in vivo as
      targets of humoral and cellular autoimmune responses directed specifically
      against normal or transformed melanocytes. These findings have provided new
      impetus to research on immune responses to melanoma and, perhaps more
      importantly, examining why they are insufficient to provide protection against
      tumour growth and what type of immune therapy can be designed to correct that.
      The melanosome must now be considered beyond its function in pigmentation, and
      assumes the role of a valuable source for specific immune targets for malignant
      melanoma.

PMID- 9167174
TI  - Inhibition of motility and invasion of B16 melanoma by the overexpression of
      cystatin C.
AB  - Although increased expression of cysteine proteinases has been shown to be
      correlated with increased metastasis for a wide variety of tumours, the
      contribution of cysteine proteinases to the metastatic spread of tumour cells is
      not well understood. In order to examine this question we have overexpressed a
      specific cysteine proteinase inhibitor, cystatin C, by stable transfection of
      B16F10 melanoma. Increased expression of cystatin C inhibited motility and in
      vitro invasiveness of B16 melanoma by 50% in both stimulated (autocrine motility
      factor, laminin) and unstimulated cells. These results suggest that cysteine
      proteinases are involved in B16 melanoma motility and invasion.

PMID- 9167175
TI  - Effect of hyperthermia on expression of histocompatibility antigens and heat
      shock protein molecules on three human ocular melanoma cell lines.
AB  - Hyperthermia is used as a new treatment modality for ocular melanoma. We wondered
      whether this treatment would affect the antigenicity of melanoma cells and
      studied the effect of hyperthermia on the expression of histocompatibility
      antigens (HLA), beta 2-microglobulin, as well as heat-shock proteins (HSP-60 and
      HSP-70) on choroidal melanoma cells. Uveal melanoma cell lines were exposed to
      different temperatures (39-45 degrees C) in a waterbath. Antigen expression was
      determined with fluorescence-activated cell sorting analysis, using monoclonal
      antibodies against HLA and HSP. In a 51Cr-release cytotoxicity assay we studied
      the effect of heat on natural killer (NK) cell susceptibility. Exposure to 45
      degrees C for 30 min reduced expression of HLA class I antigens and beta 2
      microglobulin. A greater reduction was observed after longer exposure times.
      Expression of HSP-70 was increased after exposure to 45 degrees C at all time
      intervals, while expression of HSP-60 was not induced by heat treatment. We did
      not find a significant difference in the NK cell susceptibility between heated
      and unheated cells. Hyperthermia has a time- and temperature-dependent effect on
      expression of HLA class I and HSP-70 molecules on the cell surface of uveal
      melanoma cells. Hyperthermia did not alter the susceptibility to NK cell lysis.

PMID- 9167176
TI  - An improved and combined reverse transcription-polymerase chain reaction assay
      for reliable detection of metastatic melanoma cells in peripheral blood.
AB  - The application of reverse transcription-polymerase chain reaction (RT-PCR) for
      detection of metastatic melanoma cells in peripheral blood has been used by a
      number of different scientific groups with both encouraging and discouraging
      results. We describe an improved, combined RT-PCR assay for tyrosinase mRNA,
      which can detect a single, viable melanoma cell in 10-15 ml of peripheral blood.
      The assay has been found to be highly sensitive, reproducible, cost-effective and
      clinically applicable. Furthermore, we developed a simple but effective procedure
      which prevents carry-over contamination. We present evidence indicating that the
      chance of obtaining normal melanocyte contamination with the needle prick during
      blood sampling is only 2% among all skin categories. It was found that the
      phenomenon of illegitimate transcription does not contribute to sporadic false
      positives. We conclude that the assay, as described here, is of clinical
      relevance and is a potentially powerful tool for studying various aspects of
      melanoma biology.

PMID- 9167177
TI  - D1 dopamine receptors are not expressed in human melanoma.
AB  - D1 dopamine receptor mRNA has been demonstrated in mouse melanoma cells, and the
      expression of these G-protein-coupled receptors in human melanoma was therefore
      presumed when dopamine receptor binding radiopharmaceuticals were found to be
      useful for the detection of metastases in whole-body scintigraphy. The aim of
      this study was thus to investigate if D1 dopamine receptor mRNA or protein could
      be directly demonstrated in melanoma cells. The presence of D1 dopamine receptor
      mRNA was investigated in six human melanoma cell lines from metastases using
      reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, in vitro
      binding assays with the D1 dopamine receptor agonist 125I-Sch 23982 were
      performed in 19 melanoma metastases. No D1 dopamine receptor mRNA could be
      detected by RT-PCR. All melanotic metastases were found to accumulate 125I-Sch
      23982, with the presence of binding sites and intensity of 125I-Sch 23982
      labelling correlating to the amount of melanin present in the metastases. Two
      amelanotic melanomas did not accumulate 125I-Sch 23982. D1 dopamine receptors
      could not be detected by means of RT-PCR or in vitro binding assays in human
      melanomas. Detection of antagonists is best explained by non-specific binding to
      melanin.

PMID- 9167178
TI  - Prognostic significance of nm23 protein expression in malignant melanoma. An
      immunohistochemical study.
AB  - The NM23 genes, encoding for the red blood cell nucleoside diphosphate kinases A
      and B, have been found to serve as metastasis-suppressor genes in experimental
      animal models of tumour progression, and in some, but not all cancers in man. To
      investigate the role of NM23 in the progression of human malignant melanoma, we
      studied the expression and distribution of the nm23 protein with a sensitive
      immunohistochemical technique and a well-characterized monoclonal antibody in 41
      benign pigment cell lesions and 71 uniformly treated malignant melanomas with a
      long follow up-up. In benign naevi, the junctional nests frequently expressed
      nm23 protein, whereas the immunoreactivity tended to decrease when the lesions
      matured. All malignant melanomas expressed nm23 protein in their vertical and/or
      radial growth phases, and the immunoreactivity tended to increase towards the
      deeper parts of the lesion. No relation was found between nm23 expression and
      patient outcome. In addition, nm23 was found in activated lymphoid cells, and
      this feature was significantly associated with a brisk lymphocytic stroma
      response in malignant melanomas. Our data are at variance with previous mRNA
      studies on malignant melanoma, and indicate that routine immunohistochemical
      analysis for nm23 protein on paraffin-embedded tumour tissue cannot reliably be
      used as a prognostic marker for patients suffering from malignant melanoma. In
      contrast, our findings suggest that the nm23 protein in pigment cell lesions is
      related to the proliferative or activated state of pigment cells, rather than to
      their metastatic potential.

PMID- 9167180
TI  - Effect of interferon-alpha on the expression of tumour necrosis factor-alpha by
      metastatic malignant melanoma in vivo.
AB  - To our knowledge modulation of the expression of tumour necrosis factor-alpha
      (TNF-alpha) in malignant melanoma metastases in vivo has not been reported. The
      expression of TNF-alpha by malignant melanoma cells was studied
      immunohistochemically using an anti-TNF-alpha antibody. The specificity of the
      staining reaction was demonstrated by absorption of the TNF-alpha antibody with
      human recombinant TNF-alpha, which inhibited the staining reaction. The TNF-alpha
      expression was also verified by in situ hybridization for mRNA. Metastases from
      37 patients were studied, 21 of whom were treated with IFN-alpha. All 16
      metastases from untreated patients were positive for TNF-alpha. Based on the
      average staining intensity of the melanoma cells for TNF-alpha, the metastases
      were classified into two groups. The expression of TNF-alpha varied considerably
      between metastases from different patients and also within the same metastasis.
      Melanoma cells in areas with low cellularity and large numbers of infiltrating
      inflammatory cells were generally weakly stained. This is in good agreement with
      a low staining score for TNF-alpha in metastases showing marked histopathological
      regression. Seven out of 13 patients with a low staining score for TNF-alpha
      showed a marked regression of their tumours. In contrast one out of five patients
      with a high staining score for TNF-alpha showed a marked tumour regression,
      suggesting that tumour cells sensitive to immune-mediated regression express less
      TNF-alpha. Interferon-alpha (IFN-alpha) appears to modulate the expression of TNF
      alpha. Significantly more patients treated with IFN-alpha had metastases with a
      low TNF-alpha staining score compared with untreated patients. Thus, seven out of
      21 patients treated with IFN-alpha showed a high expression of TNF-alpha in
      contrast to 13 out of 16 in the untreated group (P = 0.01).

PMID- 9167179
TI  - Natural killer and lymphokine-activated cytotoxicity following anaesthesia in
      patients with uveal malignant melanoma.
AB  - The role of enucleation in the treatment of ocular melanoma has been questioned
      by those who believe that it may increase circulating melanoma cells, increasing
      the incidence of metastases. Some aspects of the immune system are depressed by
      general anaesthesia, therefore this study was initiated to assess the effect of
      general anaesthesia on natural killer (NK) cell and interleukin-2 (IL-2)
      activated cytotoxicity in 19 patients using 51Cr-labelled target cells (K 562 and
      SW 742). NK cytotoxicity was increased at induction and during the operation
      which was due to significant increases in female, but not male patients. At 1
      week post-surgery, female patients had decreased NK cytotoxicity compared with
      males at this interval. NK cytotoxicity compared with males at this interval. NK
      cytotoxicity was increased intra-operatively when alfentanyl was used, and if the
      mean tumour diameter was > 15.0 mm the NK cytotoxicity was increased intra
      operatively compared with that in patients with smaller tumours. IL-2-stimulated
      cytotoxicity was reduced at 1 day post-surgery in females only. There was an
      increased IL-2-stimulated cytotoxicity at induction when propofol was used and IL
      2-stimulated cytotoxicity was reduced at 1 week post-operatively if the patient's
      mean tumour diameter was > 15.0 mm. If NK cell and lymphokine-stimulated cell
      cytotoxicity are involved in limiting metastatic disease, the patient' sex and
      tumour size and the anaesthetic agent used may influence the survival rates
      following surgery.

PMID- 9167181
TI  - A phase II study of interferon-alpha 2b with dacarbazine, carmustine, cisplatin
      and tamoxifen in metastatic melanoma.
AB  - A phase II trial was conducted to determine the efficacy and toxicity of the
      addition of interferon-alpha 2b (IFN-alpha) to the chemotherapy combination of
      dacarbazine (DTIC), carmustine (BCNU), cisplatin and tamoxifen (DBCT), in
      patients with stage III or IV melanoma. Treatment consisted of DTIC 220 mg/m2 and
      cisplatin 25 mg/m2 intravenously on days 1-3, BCNU 100 mg/m2 IV on day 1 only,
      tamoxifen 20 mg orally twice daily and IFN-alpha 5 x 10(6) units/m2
      subcutaneously on days 1-5. Cycles were repeated every 4 weeks. All patients
      received a loading dose of tamoxifen 100 mg orally twice daily for 5 days before
      the first course of therapy. Of the 24 patients treated, three (13%) achieved a
      complete response (CR) and six (25%) a partial response (PR), for an overall
      response rate of 38% (95% confidence interval, 17-58%). Two patients, one who
      achieved a clinical CR and one a PR, had pathologically confirmed complete
      responses. Severe myelosuppression occurred in 47% of cycles and constitutional
      symptoms were common. Overall, the addition of IFN-alpha to the DBCT regimen did
      not appear to enhance the response rate and may have increased toxicity.

PMID- 9167182
TI  - 2nd International Conference on the Adjuvant Therapy of Malignant Melanoma.
      London, UK, 14-15 March, 1997. Report and abstracts.

PMID- 9167183
TI  - Biology and biological action of the defensive secretion from a Jamaican
      millipede.

PMID- 9167184
TI  - Surface modification of polyethylene by plasma grafting with styrene for enhanced
      biocompatibility.

PMID- 9167185
TI  - Ovarian cancer patients with high CA-125 but no symptoms--should antiangiogenic
      treatments be considered?
AB  - In ovarian cancer patients, the duration of complete response after successful
      cancer chemotherapy is often short-lived. During that time period, patients
      usually receive no further maintenance therapy. Ovarian cancer patients in
      complete remission, however, often begin to show steady increases in their plasma
      levels of cancer antigen CA-125, 4-6 months before the recurrence of clinical
      symptoms. For these individuals, we are proposing the administration of
      angiogenesis inhibitors as a maintenance therapy. Although, in ovarian cancer, CA
      125 provides a unique opportunity in identifying those patients requiring further
      treatment, this concept could be applied to other forms of cancer as other
      prognostic indicators become available.

PMID- 9167186
TI  - Increased plasma serotonin following treatment with flavone-8-acetic acid, 5,6
      dimethylxanthenone-4-acetic acid, vinblastine, and colchicine: relation to
      vascular effects.
AB  - A number of antitumor agents are known to cause selective reduction in tumor
      blood flow, leading in some cases to tumor necrosis and growth delay. These
      agents include flavone acetic acid (FAA), an antitumor agent with high
      experimental but no clinical antitumor activity, 5,6-dimethylxanthenone-4-acetic
      acid (DMXAA), a highly active analogue of FAA, endotoxin, vinblastine, and
      colchicine. We find here that plasma concentrations of serotonin (5
      hydroxytryptamine) and its metabolite 5-hydroxyindole acetic acid (5-HIAA) are
      increased following administration of these agents. Mice were injected with each
      at the maximum tolerated dose and, at various times later, blood samples were
      taken, cells and platelets removed by centrifugation, and serotonin and 5-HIAA
      concentrations were measured by high performance liquid chromatography. FAA and
      DMXAA induced six- and sevenfold increases in serotonin and 5-HIAA, respectively,
      with maximal levels 4 h after drug administration. 8-Methylxanthenone-4-acetic
      acid, an inactive analogue of DMXAA, failed to increase serotonin and caused only
      a small increase in 5-HIAA. Endotoxin, vinblastine, and colchicine each caused
      increases in serotonin and 5-HIAA between 2 and 6 h after drug administration.
      The mitotic poison paclitaxel, despite inducing growth delays of Colon 38 tumors,
      did not induce tumor necrosis and caused no increase in serotonin or 5-HIAA up to
      6 h. The effect of the presence of subcutaneous Colon 38 tumors was tested and
      found not to affect the induction of increases in serotonin and 5-HIAA by DMXAA
      and colchicine. We suggest that the increases in plasma serotonin and its
      metabolite are a result of drug-induced vascular effects in host tissues, and
      that measurement of these compounds provides a potential means of monitoring
      drugs exerting vascular effects.

PMID- 9167188
TI  - Changes in lymphocyte subsets following administration of interleukin 2 and
      cyclophosphamide in mice with transitional cell carcinoma.
AB  - We investigated the effects of combination therapy with interleukin 2(IL-2) and
      cyclophosphamide (CPM) in C3H/HeN mice implanted with mouse bladder tumor cells
      (MBT2). Tumor growth was suppressed in the mice treated with IL-2 alone and mice
      treated with CPM alone, although not completely. However, tumor growth was
      completely suppressed in the mice treated with both IL-2 and CPM. As for
      lymphocyte subset analysis of the spleen using flow cytometry, the frequency of
      Lyt2+ cells and asialo GM1+ cells was significantly higher in the mice treated
      with IL-2 and CPM compared to the other groups. In the lymphocyte subset analysis
      of the thymus, the frequency of L3T4-Lyt2+ cells was significantly lower in the
      mice treated with CPM alone and mice treated with IL-2 and CPM compared to the
      other groups.

PMID- 9167187
TI  - Potentiation of the antitumor activity by a novel quinoline compound, MS-209, in
      multidrug-resistant solid tumor cell lines.
AB  - A novel quinoline compound, MS-209, was examined for its ability to reverse
      multidrug resistance (MDR) in several murine and human MDR solid tumor cell lines
      both in vitro and in vivo. MS-209 strongly reversed drug resistance to adriamycin
      (ADM) and vincristine (VCR) in acquired MDR tumor cell lines, 2780AD and KB-C1.
      In addition, MS-209 enhanced the cytotoxic effect of ADM and VCR on various human
      and murine cell lines. Particularly in 4-1St cells, which are extremely resistant
      to ADM and VCR, MS-209 at a concentration of 3 microM enhanced the cytotoxicity
      of ADM and VCR, 88- and 350-fold, respectively. MS-209 administered orally,
      together with ADM, enhanced the antitumor activity of ADM on Colon 26 and 4-1St
      tumors implanted subcutaneously (SC) in mice; the antitumor effect of ADM plus MS
      209 was higher than that of ADM alone at the maximum tolerated dose (MTD).
      Furthermore, the coadministration schedules of MS-209 to attain the highest
      potentiation of ADM activity were examined using Colon 26 tumors. The maximum
      antitumor activity was obtained when MS-209 was administered on the same day as
      ADM. MS-209 administered a day before the ADM injection exhibited no potentiation
      effect, whereas MS-209 administered a day after the ADM injection showed a
      moderate effect. The effect of MS-209 was weaker when administered in a
      fractionated manner than when administered as a single dose. The results
      presented in this article suggest that MS-209 is an effective agent to overcome
      MDR in cancer chemotherapy.

PMID- 9167189
TI  - Determinants of cytotoxicity with prolonged exposure to fluorouracil in human
      colon cancer cells.
AB  - To explore the determinants of cytotoxicity during prolonged exposure to
      pharmacologically relevant concentrations of 5-fluorouracil (FUra), we studied
      the effects of FUra at concentrations ranging from 0.1 to 1 microM in HCT 116 and
      HT 29 colon cancer cells grown in the presence of physiologic levels of
      leucovorin. A 5- and 7-day exposure to 1 microM FUra reduced cell growth to 46%
      and 20% of control in HT 29 cells and to 74% and 38% of control in HCT 116 cells.
      Concurrent exposure to thymidine (10 or 20 microM) or uridine (1 mM) provided
      partial protection against FUra toxicity in HT 29 cells, but did not protect HCT
      116 cells. After a 24-h exposure to 1 microM [3H]FUra, free 5-fluoro-2'
      deoxyuridine-5' -monophosphate (FdUMP) and FUDP. + FUTP levels were 0.7 and 144
      pmol/10(6) cells in HT 29 cells, respectively, and 3.9 and 178 pmol/10(6) cells
      in HCT 116 cells. FdUMP and FUDP + FUTP pools increased by 5.7- and 2.0-fold in
      HT 29 cells and by 1.7- and 3.3-fold in HCT 116 cells over the next 48 h, but did
      not accumulate thereafter. After a 24-h exposure to 1 microM [3H]FUra, FUra-RNA
      levels were 158 and 280 fmol/microgram in HT 29 and HCT 116 cells, respectively;
      FUra-RNA levels increased over time, and reached 700 and 1156 fmol/microgram at
      day 5. Concurrent exposure to 1 mM uridine for 72 h did not diminish [3H]FUra-RNA
      incorporation. Upon removal of [3H]FUra following a 24-h exposure, FUra-RNA
      levels remained relatively stable with 57-78% retained at 120 h. A low level of
      [3H]FUra-DNA incorporation was detected in HT 29 cells. Thymidylate synthase (TS)
      catalytic activity in control cells was 2-fold higher in HCT 116 cells compared
      to HT 29 cells (47 vs. 23 pmol/min/mg). Total TS content increased 1.5- to 3-fold
      over control in both cell lines during FUra exposure, and ternary complex
      formation was evident for up to 96 h-dTTP pools were not depleted in FUra-treated
      cells, suggesting that residual TS catalytic activity was sufficient to maintain
      dTTP pools relative to demand. Surprisingly, the partial inhibition of TS was
      accompanied by a striking accumulation of immunoreactive "dUMP" pools in both
      lines; dUTP pools also increased 2-to 3-fold. In summary, the gradual and stable
      accumulation of FUra in RNA noted in both lines may account for the thymidine
      insensitive component of FUra toxicity. Because dTTP pools were not appreciably
      diminished, the interference with nascent DNA chain elongation and induction of
      single-strand breaks in newly synthesized DNA in both cell lines may be due to
      misincorporation of deoxyuridine nucleotides.

PMID- 9167190
TI  - Frequent inactivation of the transforming growth factor beta type II receptor in
      small-cell lung carcinoma cells.
AB  - Small-cell lung cancer (SCLC) has a significantly worse prognosis than other
      forms of bronchogenic carcinoma. Because transforming growth factor beta (TGF
      beta) appears to play an important role in the pathogenesis of SCLC, we examined
      the status of the TGF-beta receptor system in a series of 11 human small-cell
      carcinoma cell lines. None of these cell lines expressed more than one-tenth the
      level of TGF-beta type II receptor (T beta R-II) gene mRNA produced by TGF-beta
      sensitive normal epithelial cells. In addition, one of the cell lines expressed a
      second truncated T beta R-II transcript, which is predicted to encode a protein
      that lacks the terminal two-thirds of the serine-threonine kinase domain. No
      other structural alterations in the promoter or coding sequences of the T beta R
      II gene were found in any of the cell lines, nor could the loss of T beta R-II
      mRNA expression be ascribed to de novo hypermethylation of promoter/enhancer
      sequences. These findings indicate that inactivation of the TGF-beta signaling
      pathway caused by the loss of T beta R-II gene expression is a common and,
      therefore, probably pathogenetically important feature of small-cell lung
      carcinoma.

PMID- 9167191
TI  - Proton magnetic resonance spectroscopy of the brain during acute hypoxia-ischemia
      and delayed cerebral energy failure in the newborn piglet.
AB  - Studies of the brains of severely birth-asphyxiated infants using proton (1H)
      magnetic resonance spectroscopy (MRS) have shown changes indicating a rise in
      cerebral lactate (Lac) and a fall in N-acetylaspartate (Naa). The aim of this
      study was to test two hypotheses: 1) that these changes can be reproduced in the
      newborn piglet after transient reversed cerebral hypoxiaischemia, and their time
      course determined; and 2) that changes in Lac peak-area ratios are related to
      changes in phosphorylation potential as determined by phosphorus (31P) MRS.
      Eighteen piglets aged < 24 h were anesthetized and ventilated. Twelve underwent
      temporary occlusion of the carotid arteries and hypoxemia, and six served as sham
      operated controls. 1H and 31P spectra were acquired alternately, both during the
      insult and for the next 48 h, using a 7-tesla spectrometer. During
      hypoxiaischemia, the median Lac/total creatine (Cr) peak-area ratio rose from a
      baseline of 0.14 (interquartile range 0.07-0.27), to a maximum of 4.34 (3.33
      7.45). After resuscitation, Lac/Cr fell to 0.75 (0.45-1.64) by 2 h, and then
      increased again to 2.43 (1.13-3.08) by 48 h. At all stages after resuscitation
      Lac/Cr remained significantly above baseline and control values. Naa/Cr was
      significantly reduced below baseline and control values by 48 h after
      resuscitation. The increases in the Lac peak-area ratios were concomitant with
      the falls in the [phosphocreatine (PCr)*]/ [inorganic phosphate (Pi)] ratio,
      during both acute hypoxiaischemia and delayed energy failure. The maximum Lac/Naa
      during delayed energy failure correlated strongly with the minimum [nucleotide
      triphosphate (NTP)]/[exchangeable phosphate pool (EPP)] (r = -0.94, p < 0.0001).
      We conclude that both hypotheses have been confirmed.

PMID- 9167192
TI  - Mild hypothermia after severe transient hypoxia-ischemia reduces the delayed rise
      in cerebral lactate in the newborn piglet.
AB  - This study tested the hypothesis that mild hypothermia after severe transient
      hypoxia-ischemia reduces the subsequent delayed rise in cerebral lactate peak
      area ratios as determined by proton (1H) magnetic resonance spectroscopy (MRS) in
      the newborn piglet. Nine piglets aged < 24 h underwent temporary occlusion of the
      common carotid arteries and hypoxemia. Resuscitation was started when cerebral
      [phosphocreatine]/[inorganic phosphate] had fallen close to zero and [nucleotide
      triphosphate (NTP)]/[exchangeable phosphate pool (EPP)] was below about a third
      of baseline. On resuscitation rectal and tympanic temperatures were lowered to 35
      degrees C for 12 h after which normothermia (38.5 degrees C) was resumed. 1H MRS
      data collected over 48 or 64 h after resuscitation were compared with
      concurrently established data from 12 piglets similarly subjected to transient
      cerebral hypoxia-ischemia, but maintained normothermic, and six sham-operated
      controls. The severity of the primary insult (judged from the time integral of
      depletion of [NTP]/[EPP]) was similar in the hypothermic and normothermic groups.
      The maximum lactate/N-acetylaspartate ratio observed between 24 and 48 h after
      resuscitation in the hypothermic group was 0.10 (0.05-0.97), median
      (interquartile range), which was significantly lower than that observed in the
      normothermic group, 1.28 (0.97-2.14), and not significantly different from that
      observed in the control group, 0.08 (0.06-0.11). Similar results were obtained
      for lactate/choline and lactate/total creatine. We conclude that mild hypothermia
      after a severe acute cerebral hypoxic-ischemic insult reduces the delayed
      elevation in lactate peak-area ratios, thus reflecting reduced lactate
      accumulation.

PMID- 9167193
TI  - Magnesium attenuates a striatal dopamine increase induced by anoxia in the
      neonatal rat brain: an in vivo microdialysis study.
AB  - We evaluated the effects of magnesium on extracellular dopamine (DA) and its
      metabolites in the striatum of 5-d-old rats submitted to 16 min of anoxia using
      microdialysis and HPLC. Rat pups were divided into three groups and received
      either 1) intrastriatal perfusion (IS) of MgSO4, 2) intraperitoneal injection
      (IP) of MgSO4, and 3) NaCl and Ringer's solution, respectively in place of MgSO4.
      After stabilization, Mg2+, saline, and Ringer's solution were administered; then,
      114 animals were exposed to 100% nitrogen for 16 min. Anoxia induced a DA surge,
      an acutely marked increase of DA, in both the control and the IP group. In
      contrast, the DA surge was significantly suppressed in the IS group (p < 0.01,
      analysis of variance). During anoxia, the plasma Mg2+ in the IP group, but not in
      the IS group, maintained a significantly higher level compared with the basal
      level. On the other hand, Mg2+ in the perfusates in the IS group, but not in the
      IP group, maintained a significantly high level during anoxia. Alterations
      induced by anoxia in other metabolites, 3,4-dihydroxyphenylacetic acid,
      homovanillic acid, norepinephrine, and 5-hydroxyindole-3-acetic acid, did not
      significantly differ among the three groups. We propose that elevated levels of
      Mg2+ in the striatum had inhibitory effects on the DA surge during anoxia.

PMID- 9167194
TI  - Ecgonine methyl ester, a major cocaine metabolite, causes cerebral vasodilation
      in neonatal sheep.
AB  - Maternal cocaine abuse has been associated with fetal and neonatal neurologic
      abnormalities, including hemorrhagic cerebral infarctions, but the mechanisms for
      cocaine's cerebral effects are unknown. We previously showed that acute cocaine
      injection causes cerebral vasodilation in cats and immature sheep; others have
      shown that cocaine causes cerebral vasoconstriction in piglets and in pressurized
      neonatal sheep arteries. Although methodologic and species differences may
      explain these conflicting results, we tested another possibility; that is, that
      ecgonine methyl ester (EME), a major cocaine metabolite in sheep, causes cerebral
      vasodilation and may account, in part, for cocaine's vascular effects. We studied
      the cerebral effects of a single i.v. injection of EME (2.5 mg/kg) in eight
      chronically catheterized, unanesthetized neonatal sheep (4 +/- 2 d old). We
      measured cerebral hemisphere blood flow (CBF) using radiolabeled microspheres,
      mean arterial pressure, heart rate, and arteriovenous oxygen content, and we
      calculated cerebral oxygen consumption (CMRo2) and cerebrovascular resistance at
      baseline and 0.5, 2, 5, and 60 min after EME injection. EME injection had no
      systemic effects, including no changes in mean arterial pressure, heart rate, or
      arterial blood gases. Within 0.5 min of injection, EME caused a 21% decrease in
      cerebrovascular resistance, which remained decreased for 60 min. CBF increased by
      20% at 0.5, 2, and 5 min. Blood flow to brain regions other than the cerebral
      hemispheres paralleled changes in CBF, with cerebellar flow remaining increased
      at 60 min. There was no change in CMRo2. There was a small, but physiologically
      insignificant, decrease in arterial oxygen content. We conclude that EME causes
      cerebral vasodilation in neonatal sheep and may account, in part, for cocaine's
      cerebral vascular effects.

PMID- 9167195
TI  - D1 and D2 dopamine receptors in perinatal and adult basal ganglia.
AB  - There is reason to believe that dopamine is important in developmental programs
      of the basal ganglia, brain nuclei implicated in motor and cognitive processing.
      Dopamine exerts effects through dopamine receptors, which are predominantly of
      the D1 and D2 subtypes in the basal ganglia. Cocaine acts as a stimulant of
      dopamine receptors and may cause long-term abnormalities in children exposed in
      utero. Dopamine receptor (primarily D1) stimulation has been linked to gene
      regulation. Therefore, D1 and D2 receptor densities in perinatal and adult
      striatum and globus pallidus were examined using quantitative autoradiography.
      The most striking finding was that pallidal D1 receptor densities were 7-15 times
      greater in the perinatal cases than in the adult. Pallidal D2 receptor densities
      were similar at both ages. In both the adult and perinatal striatum, D2 receptor
      densities were greater in the putamen than in the caudate, and both D1 and D2
      receptor densities were modestly enriched in caudate striosomes compared with the
      matrix. In both caudate and putamen, perinatal D1 receptor levels were within the
      adult range, whereas D2 receptor levels were only 50% of adult values. The
      development of D1 and D2 receptors appears to vary across the major subdivisions
      of the human basal ganglia. The facts that we found such extremely high levels of
      D1 receptors in the perinatal pallidum, and that D1 receptor activation
      influences gene regulation, suggest that the globus pallidus could be
      particularly susceptible to long-term changes with perinatal exposure to cocaine
      and other D1 receptor agonists or antagonists.

PMID- 9167196
TI  - Regulation of rat cardiac myocyte growth by a neuronal factor secreted by PC12
      cells.
AB  - Sympathetic innervation of cardiac myocytes in vitro induces growth independent
      of anatomic contact between the neurons and myocytes and is not mediated by alpha
      or beta-adrenergic receptor stimulation. To establish a model system that will
      allow purification and identification of the neuronal factor(s) responsible for
      mediating this regulation, we have initiated studies utilizing conditioned medium
      from the PC12 cell line. PC12 cells acquire a cholinergic sympathetic neuronal
      phenotype when exposed to nerve growth factor. Culture medium conditioned by
      neuronal PC12 cells, but not nonneuronal PC12 cells, induces growth in newborn
      rat cardiac myocytes as measured by surface area and [35S]methionine
      incorporation into protein and increases expression of atrionatriuretic peptide,
      a marker for myocyte hypertrophy. The magnitude of the growth response is dose
      dependent and mimics the response to sympathetic innervation. The myocyte
      response to conditioned medium is not detectable after 24 h of exposure; maximal
      rate of protein synthesis is obtained within 48 h. Neuronally differentiated PC12
      cell-conditioned medium stimulation of growth could not be mimicked by alpha- or
      beta-adrenergic agonists or muscarinic agonists, nor inhibited by alpha- or beta
      adrenergic antagonists, nor by muscarinic antagonists. Neuropeptide Y and
      somatostatin, peptides known to be present in PC12 cells and sympathetic neurons,
      were also ineffective at reproducing the effect of neuronally differentiated PC12
      cell-conditioned medium. These data indicate that neuronal cells release a
      soluble factor, different from neurotransmitter, which stimulates myocyte growth.
      They further identify the PC12 cell line as providing a convenient and abundant
      supply of this molecule, thus facilitating its further characterization.

PMID- 9167197
TI  - Hepatic and gastrointestinal oxygen and lactate metabolism during low cardiac
      output in lambs.
AB  - We previously observed young lambs to be more tolerant of hypoxia; compared with
      older lambs, they accumulate lactate at a slower rate during comparable reduction
      in cardiac output, and have a greater percent decrease in cardiac output before
      onset of systemic lactate accumulation. To determine the mechanism of lactic
      acidosis and the cause for this "tolerance," we reduced cardiac output
      progressively in seven chronically catheterized conscious lambs (16.4 + 5.1 d)
      and measured hepatic and gastrointestinal (GI) blood flow (radioactive
      microspheres) and delivery, uptake, and extraction of lactate and O2. Hepatic O2
      consumption declined proportionately below a critical hepatic O2 delivery
      (approximately 2 mL O2/min/kg), corresponding to the systemic O2 delivery
      associated with the onset of systemic lactate accumulation. As hepatic O2
      delivery decreased below the critical value, there was initially net hepatic
      lactate uptake and then a change to net production when the O2 delivery decreased
      below approximately 1 mL O2/min kg. The GI tract had net lactate production at
      rest, but surprisingly switched to lactate uptake as cardiac output decreased.
      The mechanism of lactic acidosis was failure of hepatic lactate uptake to
      increase despite increased hepatic lactate delivery, as reported in adults
      subjects. However, in contrast, there was "true" hepatic dysfunction and lactate
      production only at the lowest levels of cardiac output, after onset of systemic
      lactate accumulation. Moreover, we speculate that tolerance of young lambs to
      hypoxia is at least due to two factors: 1) hepatic lactate uptake is maintained
      beyond the "critical" O2 delivery and fall in hepatic O2 consumption, and 2)
      there is a switch to lactate uptake by the GI tract serving to buffer the
      lactate.

PMID- 9167198
TI  - Effect of hypoxia on blood glucose, hormones, and insulin receptor functions in
      newborn calves.
AB  - At between 7 and 11 h after delivery, 14 fasted calves were randomly divided into
      two groups to examine the effects of neonatal hypoxia on blood glucose metabolism
      and its mechanisms. One group was subjected to breathe a gas mixture containing
      4.8-5.9% oxygen in nitrogen from a hood for 2 h. The second control group
      breathed atmospheric gas. Several possible causes of changes in blood glucose
      were assessed, including insulin, glucagon, and hydrocortisone as prereceptor
      factors, insulin binding as a receptor factor, and insulin receptor tyrosine
      kinase (IR-TK) activity as a postbinding factor. The hypoxic animals exhibited
      increased concentrations of blood glucose (from 5.47 +/- 1.61 mmol/L to 7.97 +/-
      1.30 mmol/L), plasma insulin, and hydrocortisone, but decreased concentrations of
      glucagon. The percentage of specific binding activity decreased in the hypoxic
      group compared with the control group (12.71 +/- 1.25% versus 15.14 +/- 1.27%, p
      < 0.01). Several parameters of insulin receptor binding, i.e. affinity constants,
      high and low binding capacities, and numbers of binding sites, showed a tendency
      to decrease after hypoxia. Only lower affinity binding sites decreased
      significantly. At the postreceptor level, IR-TK activity was decreased in the
      hypoxic group compared with controls. It is concluded that hypoxia induced
      insulin resistance in these newborn calves. The results suggest that the primary
      mechanism for insulin resistance in the hypoxic newborn was reduced insulin
      receptor responsiveness with attenuated activity of IR-TK at the postreceptor
      level.

PMID- 9167199
TI  - Effect of tactile stimulation on serum lactate in the newborn rat.
AB  - Maturation of the CNS in neonatal animals is dependent upon both sensory input
      and the constant availability of metabolic fuel. Previous reports indicate that
      the preferred metabolic substrate for the developing rat brain is lactate. In
      this study, we used the neonatal Sprague-Dawley rat to investigate a possible
      interactive role between touch and the regulation of serum lactate. Two hundred
      and fifty rats (postnatal d 0-7) were exposed to a standard tactile stimulation
      (TS) regimen to mimic nonspecific maternal stimulation. This regimen consisted of
      stroking the dorsum with a soft camel hair brush for 30 s every minute for 10
      min. Serum lactate and glucose levels were measured after TS. In newborn (d 0)
      rats, lactate levels were increased by 207% in stroked pups versus controls. This
      elevation of serum lactate persisted for 30 min after cessation of TS. On d 7, TS
      increased lactate only 11%. Glucose levels were unaffected at all ages. In
      neonatal pups, pretreatment with pentobarbital blocked the effect of TS, whereas
      epidermal growth factor evoked a synergistic response. Capsaicin pretreatment had
      no effect. Mixed arteriovenous blood gases revealed a mild increase in pH and a
      decrease in Pco2 after TS. We conclude that TS in newborn rats is a regulator of
      circulating lactate. This response is maximal in the immediate postnatal period
      and wanes over the 1st wk of life. We speculate that the transduction of sensory
      signals by the skin is a mechanism regulating the availability of cerebral energy
      substrates in the newborn mammal.

PMID- 9167200
TI  - Influence of sleep states on laryngeal and abdominal muscle response to upper
      airway occlusion in lambs.
AB  - This study was aimed at describing abdominal and laryngeal muscle responses to
      upper airway occlusion (UAO) in early life and the effect of sleep states on
      these responses. Twelve nonsedated, 9-26-d-old lambs were studied. We
      simultaneously recorded 1) airflow (pneumotachograph + face mask); 2) sleep
      states (electrocorticogram and electrooculogram); 3) abdominal muscle (external
      obliquus) electromyogram (EMG); and 4) glottic constrictor (thyroarytenoid) and
      dilator (posterior cricoarytenoid and cricothyroid) muscle EMGs. The
      pneumotachograph was repeatedly occluded for 15-30 s in wakefulness and natural
      sleep. We analyzed 90 occlusions during wakefulness (11 lambs), 28 during non
      rapid eye movement (nREM) sleep (six lambs), and 23 during rapid eye movement
      (REM) sleep (five lambs). A phasic expiratory external obliquus EMG was present
      during baseline and progressively increased throughout UAO in wakefulness and
      nREM sleep, but not in REM sleep. Phasic thyroarytenoid EMG progressively
      increased during inspiratory efforts throughout UAO in wakefulness and nREM
      sleep, paralleling the increase in glottic dilator (posterior cricoarytenoid and
      cricothyroid) EMG. In contrast, glottic muscle response to UAO in REM sleep was
      severely blunted or disorganized by frequent swallowing movements. We conclude
      that UAO triggers complex and coordinated laryngeal and abdominal muscle
      responses during wakefulness and nREM sleep in lambs; these responses are largely
      absent, however, in REM sleep. These unique results, together with the defective
      arousal response in REM sleep, suggest that vulnerability to airway occlusion
      could be increased during REM sleep in early life. Possible implications for
      understanding severe postnatal apneas are discussed.

PMID- 9167201
TI  - Effects of dexamethasone on acute virus-induced airway dysfunction in adult rats.
AB  - Respiratory viral infections have been associated with airway obstruction and
      hyperresponsiveness, and exacerbations of asthma. Although virus-induced asthma
      is thought to be precipitated by airway inflammation, the clinical efficacy and
      rationale for using antiinflammatory treatment during such exacerbations remains
      controversial. The purpose of this study was to use a well characterized animal
      model of respiratory viral illness to test the hypothesis that the inflammatory
      response to viral infection is responsible for the development of airway
      dysfunction. Adult rats were inoculated with either Sendai virus or sterile
      vehicle and treated with daily injections of dexamethasone or saline. At
      postinoculation d 4, 5, or 6, rats were evaluated for airway obstruction,
      hyperresponsivenes, inflammation, and lung viral titers. Saline-treated infected
      rats had significant airway obstruction (increased resistance, decreased dynamic
      compliance), hyperresponsiveness (i.v. methacholine), and inflammation (increased
      bronchoalveolar lavage leukocytes) compared with noninfected controls. In
      contrast, dexamethasone-treated infected rats had no increase in bronchoalveolar
      lavage leukocytes and significantly smaller changes in airway physiology, but had
      increased lung viral titers compared with saline-treated infected rats. We
      conclude that glucocorticoid suppression of the inflammatory response to
      respiratory viral infection largely prevents virus-associated airway dysfunction.

PMID- 9167202
TI  - CD95-induced apoptosis contributes to loss of primed/memory but not resting/naive
      T cells in children infected with human immunodeficiency virus type 1.
AB  - Increased apoptosis of uninfected CD4+ T cells is involved in CD4+ T cell
      depletion in HIV-1+ individuals. Recently, a progressive loss of resting naive T
      cells has been shown during the asymptomatic stage of HIV infection in children
      and adults. The CD95 receptor/ligand system is a key regulator of T cell
      apoptosis. To elucidate the role of this system in the depletion of resting naive
      T cells, we studied expression of CD95 and sensitivity toward CD95-triggered
      apoptosis in T cell subsets defined by CD45 (leukocyte common antigen) isoforms
      and CD62L (lymphocyte homing receptor L-selectin) in a cohort of HIV-1+ children.
      In patients and healthy control subjects the level of CD95 expression increased
      from resting/naive (L-selectin(bright) CD45RA+) T cells to primed/memory (CD45RO+
      CD45RA-) T cells. In HIV-1+ children the susceptibility of peripheral blood T
      cells for CD95-mediated apoptosis also increased with progressive differentiation
      toward primed/memory T cells. Resting/ naive T cells were resistant to
      spontaneous and anti-CD95-induced apoptosis. Loss of naive (CD45RA+ CD45RO-) T
      cells in HIV-1+ patients in vivo was found to be paralleled by an increase in the
      percentage of CD95high T cells as well as an increase in anti-CD95-induced
      apoptosis of CD4+ and CD8+ T cells. We conclude that loss of naive unprimed T
      cells during the asymptomatic phase of HIV-1 infection is caused by continuous
      generation of primed cells that exhibit increased sensitivity toward CD95
      mediated apoptotic cell death in vitro.

PMID- 9167203
TI  - Effect of exogenous and endogenous nitric oxide on the airway and tissue
      components of lung resistance in the newborn piglet.
AB  - Despite widespread reports of the vasodilatory actions of nitric oxide (NO),
      little is known of the relaxant effect of NO on newborn airways or lung
      parenchymal structures. We studied the effects of inhaled NO at 20, 40, and 80
      ppm on lung (Rl), tissue (Rti), and airway (R(aw)) resistance in 13 2-5-d-old
      anesthetized, ventilated, open-chested piglets. Rl was measured from
      transpulmonary pressure and air flow. Rti was measured by alveolar capsules, and
      R(aw) was calculated as the difference between Rl and Rti. Any given
      concentration of inhaled NO (20, 40, or 80 ppm) significantly decreased Rl (p <
      0.001), Rti (p < 0.001), and R(aw) (p < 0.05). In addition, blockade of
      endogenous NO with 30 mg/kg N omega-nitro-L-arginine methyl ester (L-NAME) given
      i.v. in 12 piglets significantly increased Rti and Rl with variable changes in
      R(aw), and caused a decrease in dynamic compliance. Readministration of NO to
      eight piglets induced a significant decreased in Rl and Rti at 20 and 80 ppm,
      whereas R(aw) significantly decreased only at 80 ppm. Pulmonary arterial pressure
      decreased after exposure to inhaled NO and increased after L-NAME administration.
      Systemic arterial pressure was unaffected by inhaled NO but increased after L
      NAME administration. Our results indicate that Rl, R(aw), and Rti are reduced by
      exogenous NO, suggesting NO-mediated airway smooth muscle relaxation throughout
      the newborn lung. In contrast, blockade of endogenous NO significantly increases
      only Rti, suggesting a physiologic role for endogenous NO in regulation of
      peripheral contractile elements. We speculate that NO-mediated modulation of
      resistance in pulmonary parenchyma may serve to regulate the balance of
      ventilation and perfusion and resultant gas exchange in the lungs during early
      postnatal development.

PMID- 9167204
TI  - [18F]fluorodeoxyglucose uptake in neonatal acute lung injury measured by positron
      emission tomography.
AB  - The objective of this study was to evaluate positron emission tomography (PET) of
      [18F]fluorodexoyglucose (18FDG) uptake as a measure of neonatal acute lung
      injury. Inasmuch as intrapulmonary sequestration of neutrophils is a hallmark of
      acute lung injury, quantification of neutrophil activity using 18FDG may offer a
      novel, in vivo technique to examine the progression and resolution of this
      disease. Ten newborn piglets were studied: six received bronchoalveolar lavage
      followed by 4 h of high pressure ventilation of create acute lung injury. Four
      healthy piglets served as controls. 18FDG (0.8 mCi/kg; 29.6 MBq) was given i.v.
      and PET (ECAT 953/31, Siemens) was performed for 90 min. During PET, all animals
      were sedated, paralyzed, and ventilated to maintain normal blood gases. The time
      course of radioactivity in lung regions and in plasma was used to calculate the
      rate constant for the metabolic trapping of 18FDG in tissue according to the
      method of C. S. Patlak. Median 18FDG influx constants were significantly higher
      in injured piglets (0.0187 min-1) than in control piglets (0.0052 min-1) (p <
      0.01). Moreover, consistent with the 18FDG uptake data, injured piglets had
      moderate to severe injury on lung histology whereas control piglets had only
      slight and focal histologic changes. We conclude that PET of 18FDG uptake is an
      accurate, readily repeatable in vivo measure of neonatal acute lung injury.

PMID- 9167205
TI  - Doppler velocimetry in branch pulmonary arteries of normal human fetuses during
      the second half of gestation.
AB  - The objective of the present study was to determine the characteristics of
      Doppler flow velocity wave forms in branch pulmonary arteries in relation to
      gestational age. A total of 111 singleton normal pregnancies were studied during
      the second half of pregnancy using a combined color-coded Doppler and two
      dimensional real-time ultrasound system. Pulsed Doppler measurements of the most
      proximal branch of the right or left pulmonary artery were attempted during fetal
      apnea from a transverse cross-section of the fetal chest at the level of the
      cardiac four-chamber view after visualization with color Doppler. The success
      rate in obtaining the pulmonary arterial wave form was 85%. The wave form
      displayed a rapid systolic velocity acceleration, followed by an initially rapid
      but then more gradual velocity deceleration which was interrupted in most cases
      by a short reversed flow interval at the beginning of the diastolic phase of the
      cardiac cycle. The diastolic phase was characterized by forward flow. Peak
      systolic, end-diastolic and time-averaged velocity, pulsatility index, and
      systolic integral remained constant during gestation. Changes in vessel diameter
      or compliance may play a role in this. A gestational age-dependent rise was
      established for peak diastolic velocity, diastolic integral, and early peak
      diastolic reverse flow, whereas a gestational age-determined decline was found
      for the peak systolic/peak diastolic ratio. Fetal heart rate demonstrated a
      statistically significant increase relative to gestational age. However, the
      observed relation between the flow velocity wave form parameters, pulsatility
      index calculations, and gestational age was independent of fetal heart rate. It
      is speculated that peak diastolic velocity, diastolic integral, and peak
      systolic/peak diastolic ratio rather than the pulsatility index are useful in
      detecting gestational age-related changes in human fetal pulmonary vascular
      resistance.

PMID- 9167206
TI  - Plasma somatostatin and cholecystokinin levels in preterm infants during their
      first two years of life.
AB  - Plasma somatostatin and cholecystokinin are two gut peptides with opposite
      functions which are regulated by two different parts of the autonomic nervous
      system. Previously we have shown that plasma somatostatin and cholecystokinin
      levels are higher in preterm infants during the 1st d of life than in adults or
      in their mothers, and that plasma somatostatin is negatively correlated to
      gestational age. We have longitudinally studied these two peptides in 28 preterm
      infants, 17 boys and 11 girls, up until the age of 2 y. The mean (SD) gestational
      age was 32.3 (2.8) wk, the mean birth weight was 1877 (515) g, and the mean birth
      length was 42.8 (3.8) cm. Blood samples were taken on the 1st d of life, at 6 wk,
      and at 3, 6, 12, and 24 mo of age. Plasma was analyzed by specific somatostatin
      and cholecystokinin RIAs. The median plasma somatostatin and cholecystokinin
      levels were lowest at 3 mo (somatostatin = 17.4/cholecystokinin = 10.5 pmol/L)
      and highest at 6 mo (somatostatin = 37.3/cholecystokinin = 27.1 pmol/L). At 24 mo
      plasma somatostatin remained at the same level, and cholecystokinin had decreased
      to half that level. After the 1st d of life plasma somatostatin and
      cholecystokinin levels were not correlated to gestational age or attained weight
      or length. The plasma somatostatin level at 3 mo of age was negatively correlated
      to the increment in knee-heel distance between 3 and 6 mo of age.

PMID- 9167207
TI  - Changes of angiogenin serum concentrations in the perinatal period.
AB  - The polypeptide angiogenin, a normal constituent of human plasma, might be
      involved in endothelium homeostasis, angiogenesis, and neovascularization
      accompanying various diseases. This study aimed at determining angiogenin serum
      concentrations in the perinatal period of healthy newborns and at forming a
      baseline for this protein, which in the future may serve as a diagnostic index in
      developmental errors of the placenta and/or newborn. One milliliter of blood was
      drawn on d 1 and 4 of life from 30 healthy full-term neonates, and angiogenin
      serum concentrations were measured by an enzyme immunoassay using a commercially
      available kit. In 10 cases angiogenin serum concentrations were also measured in
      the maternal serum before delivery and in the umbilical vein serum. Angiogenin
      serum concentrations (microgram/L) were significantly higher in maternal serum
      (225.7 +/- 49.6) compared with umbilical vein serum (119.0 +/- 34.2) (p <
      0.0002), as well as that compared with day 1 (166.4 +/- 44.9) (p < 0.01) but not
      to d 4 neonatal serum (240.8 +/- 52.6). Angiogenin serum concentrations showed a
      statistically significant increase from d 1 to 4 (p < 10(-7)), as well as from
      umbilical cord serum to d 1 neonatal serum (p < 0.0002). A statistically
      significant correlation existed between values in umbilical cord serum and d 1
      neonatal serum (r = 0.84, n = 10, p < 0.002) and between those in d 1 and 4
      neonatal serum (r = 0.37, n = 30, p < 0.04). Sex, birth weight, or mode of
      delivery did not influence angiogenin serum concentrations. We conclude that a
      rapid increase of angiogenin serum concentrations to maternal levels takes place
      during the first four postnatal days in healthy full-term neonates.

PMID- 9167208
TI  - Age of onset of streptozocin diabetes determines the renal structural response in
      the rat.
AB  - Prepubertal years of insulin-dependent diabetes mellitus are protected from the
      nephropathic effects of this disease, yet this effect of immaturity has not been
      investigated in an animal model. Male Munich-Wistar rats were made diabetic with
      streptozocin at two ages: weanling (approximately 4 wk) and pubescent
      (approximately 10 wk). After 5 wk of untreated diabetes, weanling diabetic
      animals showed relatively greater growth of the medulla, whereas relative
      proportions of these areas were constant in the older animals. Glomerular volume
      increased by approximately 35% in older diabetic animals, but no glomerular
      enlargement was demonstrated in weanling rats with diabetes. Glomerular
      ultrastructure was not significantly altered during the short course of this
      study. The renal structural response to diabetes is age-dependent in the rat,
      with prepubertal animals protected from glomerular hypertrophy. Longer studies
      are needed to see if these differences will eventually parallel those
      demonstrated in patients with onset of diabetes before and after puberty. This
      model may ultimately prove to be valuable in determining the mechanism via which
      prepubertal kidneys are protected from the nephropathic effects of insulin
      dependent diabetes mellitus.

PMID- 9167209
TI  - Circulating red cell volume and red cell survival can be accurately determined in
      sheep using the [14C]cyanate label.
AB  - The sheep commonly serves as an animal model for investigation of human fetal and
      newborn erythropoiesis and red blood cell kinetics. Measurement of red cell
      volume (RCV) and survival (RCS) in sheep would be useful for studying mechanisms
      of neonatal anemia. Unfortunately 51Cr, the standard method for RCV, is not
      suitable for RCS in sheep because 51Cr leaves the red cell too rapidly. We
      developed and validated the permanent label [14C]cyanate as a method for
      measuring both RCV and RCS in sheep. In 19 sheep, RCV was determined
      simultaneously using [14C]cyanate and 51Cr. RCV determined by [14C]cyanate agreed
      almost perfectly with RCV by 51Cr; correlation coefficient = 0.990. The line of
      regression had a slope of 0.94 and an intercept of 40; these parameters are not
      significantly different from a line of identity. In nine sheep, RCS was
      determined using [14C]cyanate. Survival after d 1 accurately fit a model
      containing two components: 1) an early exponential loss likely related to damage
      caused by labeling and handling and 2) a linear decrease that reflected normal
      survival of undamaged red cells. Mean potential life span (MPL) determined from
      the linear phase was 114 +/- 12 d (mean +/- 1 SD). These results agree with
      reported MPL values determined either by 59Fe or differential hemolysis.
      Together, these observations establish [14C]cyanate-labeled red cells as a tool
      for measuring both RCV and RCS in sheep and enhance the value of the ovine model
      for investigating neonatal anemia.

PMID- 9167210
TI  - Effect of prostaglandin E1 infusion in severe chronic heart failure.
AB  - Prostaglandin E1 (PGE1, alprostadil) is a potent vasodilating agent that is
      frequently used to resolve cardiogenic pulmonary hypertension. To investigate the
      effect of PGE1 in refractory chronic heart failure in a double-blind trial,
      twenty patients (17 men, 3 women, 58 +/- 2 years, cardiac index < or = 2.5
      l/min/m2, pulmonary capillary wedge pressure > or = 20 mmHg), who were in NYHA
      functional class IV on optimized treatment with ACE inhibitors and furosemide
      were infused with 30 ng/kg/min PGE1 or placebo through 48 hours. All patients
      received a concomitant therapy with standardized catecholamine infusions which
      were given 24 hours in advance and were continued throughout the study. There was
      no difference in baseline values between the randomized groups before PGE1 or
      placebo was added. PGE1 resulted in decrements in pulmonary artery pressure (from
      37 +/- 4 to 30 +/- 4 mmHg; p < 0.01), pulmonary capillary wedge pressure (from 26
      +/- 4 to 19 +/- 3 mmHg p < 0.001) systemic vascular resistance index (from 2048
      +/- 213 to 1506 +/- 13 dyn.sec/cm5.m2, p < 0.05) and in increments in cardiac
      index and stroke volume index (from 2.2 +/- 0.1 to 2.8 +/- 0.2 l/min.m2; p < 0.05
      and from 23 +/- 2 to 28 +/- 2 l/m2; p < 0.05, respectively). Moreover, creatinine
      clearance increased (p < 0.05). Placebo infusions did not result in any
      hemodynamic or renal effect. Between groups percentage hemodynamic changes
      differed with respect to pulmonary artery pressure (p < 0.01), cardiac index (p <
      0.05), stroke volume index (p < 0.05) and pulmonary vascular resistance index (p
      < 0.05). It is concluded that intravenous infusions with PGE1 may add further
      substantial benefit to the hemodynamic state in refractory heart failure patients
      who are already stabilized on i.v. inotropic support with catecholamines.

PMID- 9167211
TI  - Differential sensitivities of human blood monocytes and alveolar macrophages to
      the inhibition of prostaglandin endoperoxide synthase-2 by interleukin-4.
AB  - Interleukin-4 (IL-4) is a potent immunomodulatory cytokine synthesized and
      released by Th2 lymphocytes, mast cells and basophils. It has important effects
      on monocyte/macrophage cell lines, regulating the secretion of several cytokines,
      and the production of eicosanoids. In human monocytes and macrophages, IL-4
      increases the expression of 15-lipoxygenase and 15-HETE production, but
      suppresses the inducible isoform of the prostaglandin H synthase (PGHS-2) enzyme
      and prostanoid synthesis. Prostanoids, in particular prostaglandin E2 (PGE2) have
      important functions in modulating inflammatory and fibrotic processes. We
      compared the effect of IL-4 on the expression of PGHS-2 in human alveolar
      macrophages (AM) and blood monocytes (BM) activated with physiologically distinct
      stimuli, lipopolysaccharide (LPS) or IL-1 in vitro. The induction of PGHS-2 mRNA
      and protein, and prostanoid synthesis by all stimuli was inhibited by exogenous
      IL-4 in both cell types. However, monocytes were more susceptible to this effect
      of IL-4 than alveolar macrophages.

PMID- 9167212
TI  - Prostaglandin E and F2 alpha concentration in the cervical mucus and mechanism of
      cervical ripening.
AB  - OBJECTIVE: To study the mechanism of cervical ripening by determination of
      prostaglandin E (PGE) and F2 alpha (PGF2 alpha) concentrations in cervical mucus
      during the course of pregnancy. STUDY DESIGN: Cervical mucus was collected from
      99 pregnant women attending the mother care unit of the department. Women with
      sexual intercourse within the last 24 hours before sampling and subjects with
      bacterial vaginosis were analysed separately. RESULTS: Eleven women had sexual
      intercourse within 24 hours before sampling. The concentration of PGE in their
      cervical mucus was high corresponding to 2000-4000 pg/mg w w lasting for a period
      of 10-12 hours postcoitally, whereas the levels of PGF 2 alpha only increased
      slightly. Bacterial vaginosis was accomplished by a slight but significant
      elevation of PGF2 alpha levels but only of a minor increment of the PGE values.
      The prostaglandin concentrations in the mucus from the remaining 68 women were
      for PGE 102.75 +/- 111.51 and for PGF2 alpha 97.54 +/- 82.48 pg/mg w w (mean +/-
      SD). Although the values were scattered the concentrations remained at
      approximately the same level throughout pregnancy and there was no tendency
      towards an increment during the last weeks of pregnancy when cervical maturation
      is apparent. CONCLUSION: Cervical softening seems not to be accomplished by a
      massive local release of prostaglandins but rather the result of a number of
      different mechanisms more or less influenced by minor alterations of
      prostaglandin synthesis and release. Involved in these mechanisms are probably
      neutrophil-derived collagenases.

PMID- 9167213
TI  - Different effects of a thromboxane mimetic on blood flow and plasma exudation in
      guinea pig airways and skeletal muscle.
AB  - Thromboxane A2 (TXA2) is a potent constrictor of both airway and vascular smooth
      muscle. In addition, plasma exudation is induced in the airways by a thromboxane
      mimetic (U-46619). Because plasma exudation is associated with a local
      vasodilatation and increased local blood flow, we hypothesized that the general
      vasoconstrictor effect of U-46619 would be weaker in the airways than in other
      vascular beds, perhaps resulting in increased local airway blood flow. We studied
      the effects of i.v. U-46619 on blood pressure, lung resistance as well as blood
      flow, plasma exudation in airways and leg skeletal muscle in guinea pigs. We
      found (1) i.v. U-46619 increases the systemic blood pressure, blood flow in
      tracheal mucosa but decreases blood flow in leg skeletal muscle; (2) i.v. U-46619
      induces plasma exudation in the airways, but not in the leg skeletal muscle; (3)
      a positive relationship between blood pressure and tracheal blood flow as well as
      airway plasma exudation, a negative relationship between blood pressure and blood
      flow in leg skeletal muscle; (4) i.v. U-46619 significantly increases lung
      resistance. We conclude that i.v. U-46619 induces plasma exudation in airways but
      not in skeletal muscle, and that this plasma exudation is associated with the
      increased local blood flow, which in turn is caused by increased inflow pressure
      and redistribution of the total body blood flow to the airways.

PMID- 9167215
TI  - Drinking by adolescents in the European Community.

PMID- 9167214
TI  - Anti-inflammatory effects of beraprost sodium, a stable analogue of PGI2, and its
      mechanisms.
AB  - We examined whether beraprost sodium (beraprost), a stable analogue of PGI2, has
      an anti-inflammatory effect on the permeability barrier through endothelial cells
      in vivo. The injection of collagen (5 micrograms/head) plus epinephrine (0.6
      microgram/head) showed time-dependently the increased Evans blue dye leakage of
      the lung in mice for 60 min. Beraprost significantly suppressed this leakage dose
      dependently (control; 11.26 +/- 1.64 micrograms/lung, beraprost 10 micrograms/kg;
      7.49 +/- 1.36 micrograms/lung, 30 micrograms/kg; 5.33 +/- 0.71 micrograms/lung,
      100 micrograms/kg; 5.52 +/- 0.79 micrograms/lung). Pulmonary thromboembolism
      induced Evans blue dye leakage was also reduced significantly by aspirin (5
      mg/kg), but PGE1 (170 micrograms/kg) showed a tendency to potentiate the
      edematogenic response. One week after the injection of same dosage of collagen
      plus epinephrine in mice, pulmonary thromboembolism showed the increase of wet-to
      dry weight ratio of the lung (normal; 3.84 +/- 0.01, control; 3.96 +/- 0.04) and
      right ventricular hypertrophy (normal; 28.2 +/- 0.9%, control; 32.3 +/- 0.9%)
      compared to normal mice. Beraprost significantly suppressed lung edema and
      hypertrophy dose-dependently, and over 30 micrograms/kg/day of beraprost, the
      effects were statistically significant (beraprost 30 micrograms/kg/day; 3.85 +/-
      0.02 and 27.8 +/- 1.4%, 100 micrograms/kg/day; 3.85 +/- 0.02 and 27.3 +/- 1.1%).
      Beraprost significantly reduced 5-hydroxytryptamine (5-HT; 17 nmol/paw)-induced
      rat paw edema dose-dependently (5-HT alone; 100%, beraprost 10(-13) mol/paw;
      91.19 +/- 2.22%, 10(-12) mol/paw; 85.79 +/- 4.85%, 10(-11) mol/paw; 78.49 +/-
      3.95%). 5-HT-induced edema was also suppressed significantly by the co-injection
      of (-)-isoproterenol (10(-12) mol/paw), but PGE1 (10(-11) mol/paw) significantly
      potentiated the edematogenic response. From these results, we propose that the
      anti-inflammatory effect of beraprost may be contributed, in part, to the
      permeability barrier through end othelial cells in vivo.

PMID- 9167216
TI  - Mast cells as potent inflammatory cells.
AB  - In the last decade, new information was achieved on mast cells (MC). Their origin
      is assumed to be different from that of the basophils. There are two types of MC
      with differences in structure, distribution and function: conjunctival and
      mucosal. MCs are among the most important cells in the development of allergic
      inflammation through the cytokines and mediators released on the activation of
      the surface receptors (high-affinity receptors for IgE: Fc epsilon R1). The
      cytokines released by MCs, e.g., interleukin 5 (IL5), IL8, are chemoattractants
      for eosinophils and neutrophils, respectively. The two types of mediators
      released by MC-those preformed, such as histamine, tryptase, serotonin, and the
      newly-synthetized ones, such as prostaglandin D2 (PGD2), leukotrienes C4 (LTD4),
      D4 (LTD4), E4 (LTE4), induce vasodilatation, bronchoconstriction, cellular
      chemotaxis, increase vascular permeability. The involvement of MC in many human
      diseases was shown within in vivo and in vitro studies (in allergy, lung
      fibrosis, atherosclerosis, carcinogenesis, etc.).

PMID- 9167217
TI  - Serum lactate dehydrogenase and alkaline phosphatase activities and serum
      cholesterol level in bone marrow blood.
AB  - Serum cholesterol level as well as serum lactate dehydrogenase (LDH), alkaline
      phosphatase (ALP) and gamma-glutamyl transferase (GGT) were measured in 65
      samples of bone marrow blood and in matched peripheral blood taken from patients
      with various hematological diseases. As expected, serum LDH activities were
      higher and serum total cholesterol levels were lower in the bone marrow blood
      than in the blood taken from the cubital vein. More interestingly, an important
      increase of heat-labile ALP, but not of serum GGT, was found in the bone marrow
      blood obtained from patients characterized by a proliferating bone marrow.
      Actually, both LDH and ALP activities were obviously higher in the bone marrow
      blood of patients with megaloblastic anemia, myelodysplastic syndrome and chronic
      myeloid leukemia than in samples taken from patients with chronic lymphocytic
      leukemia, a disease characterized by a slower proliferation rate. While the
      expected increased LDH activity is the result of an accelerated turnover of bone
      marrow cells implying the release of this enzyme from the dividing and/or
      decaying cells, the much higher activity of the heat-labile alkaline phosphatase
      found in the bone marrow blood would reflect an enhanced local remodeling of bone
      structures, probably related to an expanded proliferating bone marrow. The lower
      serum cholesterol level in the bone marrow blood could be subsequent to an
      enhanced uptake of low density lipoproteins by specific receptors on the bone
      marrow cells.

PMID- 9167218
TI  - Complete atrioventricular block in patients with acute inferior myocardial
      infarction. Clinical spectrum and prognostic significance.
AB  - Patients with acute inferior myocardial infarction (IMI) and complete
      atrioventricular block (CAVB) have a wide range of mortality rate. This raises
      the question whether there is no other risk factor that interferes in this
      particular situation. In our study, mortality rate in patients with acute IMI and
      CAVB was significantly greater than in patients without conduction disturbance,
      but the occurrence of right ventricle myocardial infarction (RVMI) enhanced the
      mortality rate regardless of the presence or absence of CAVB.

PMID- 9167219
TI  - The effect of low-dose amiodarone in prevention of paroxysmal atrial
      fibrillation.
AB  - The efficacy of amiodarone for atrial fibrillation (AF) prophylaxis is well
      established, but the large doses used until recently may be harmful during long
      term therapy, especially because of the pulmonary fibrosis it generates.
      Recently, similar good results have been reported in using low-dose amiodarone.
      We studied the prophylactic effect of long-term therapy of low-dose amiodarone
      (200 mg/day) in 26 patients with AF of various etiologies. During a period of six
      months to four years, 46% of patients were free of any arrhythmic attack. The
      paroxysmal attacks of AF continued in 35% of patients, but with a lower
      frequency. In 19% of patients AF became chronic during amiodarone therapy. The
      best results were registered in patients over sixty, with stable sinus rhythm in
      75% of cases, probably in relation to the ischemic etiology of AF and the anti
      ischemic associated effect of amiodarone. The stability of sinus rhythm was
      greater (50% vs 38%, p < 0.05) when the treatment with amiodarone was started
      within the first six months from the first AF attack. Our results supported the
      use of low-dose amiodarone as a first-line drug for the long-term prophylaxis of
      AF, mainly in older patients.

PMID- 9167221
TI  - Acute myocardial infarction and acute "stress ulcer".
AB  - Six patients (males, mean age 45 years) who developed gastroduodenal "stress"
      ulcerations following an acute myocardial infarction (AMI) were studied. In these
      subjects no previous digestive disease symptoms had been mentioned. The clinical
      pattern of the "stress ulcer" is often atypical. Stomach seems to be the
      preferred site of "stress ulcer", which generally appears under the form of
      multiple lesions. Acute "stress ulcer" prognosis is very severe, due to the high
      rate of mortality (five out of the six cases in this report).

PMID- 9167220
TI  - Electrophysiologic evaluation of extrinsic and intrinsic sinus node dysfunction.
AB  - Electrophysiologic investigation was done for ten patients with clinical and ECG
      criteria for sick sinus syndrome (SSS). Sinus node function was assessed through
      corrected sinus node recovery time (CSNRT) and sinoatrial conduction time (SACT),
      before and after autonomic blockade (AB) with propranolol 0.2 mg/kg and atropine
      0.04 mg/kg, given intravenously. Four patients having electrophysiologic
      parameter in normal range before AB were not considered as SSS. In three patients
      extrinsic sinus node dysfunction (SND) was found, the pathologic values of CSNRT
      and SACT being normal after AB, and in one patient with sinus bradycardia, the
      sinus node function was difficult to be appreciated. In two patients only
      intrinsic SND was found and, in consequence, pacemaker device was implanted.

PMID- 9167222
TI  - Interdependence between Zn and Cu serum concentrations and serum immunoglobulins
      (IgA, IgM, IgG) in liver diseases.
AB  - The object of this study was to find out, by means of statistical-mathematical
      methods, whether the serum concentrations of Zn and Cu had a role in the
      interrelation among immunoglobulins IgA, IgM, IgG in four groups of subjects with
      various forms of liver diseases. It was found that the correlation structure
      between IgA, IgM, IgG and the serum concentration of Zn or Cu were different in
      the four types of diseases studied, and also that of these two metal ions, Zn was
      the most important, influencing the interdependence between the immunoglobulins
      in the active forms of disease.

PMID- 9167223
TI  - Colonic transit investigated by radiopaque markers in females with irritable
      bowel syndrome: no correlation with symptoms and chronic stress.
AB  - The aim of this study was to investigate the correlation between colonic transit
      and chronic stress in the irritable bowel syndrome (IBS). Total and segmental
      colonic transit was studied with radiopaque markers in 16 females with irritable
      bowel syndrome and in 20 matched controls. The transit times were correlated with
      symptoms and with scores of some psychological tests reflecting stress or
      susceptibility to stress: the life events scale of Holmes and Rahe, the Jenkins
      activity survey for type-A behaviour, the MMPI hostility scale and the Dukes
      questionnaire for social support. In females with irritable bowel syndrome,
      prolonged transit was observed on the right colon in 43% of cases, on the left
      colon in 25% of cases, on the rectosigmoid in no case, on the total colon in 31%
      of cases. No subject had accelerated colonic transit. In irritable bowel
      syndrome, life events scores were high in 63% of cases, 69% had type-A behaviour,
      50% had high scores for hostility and 69% had impaired social support. All these
      parameters were impaired as compared to controls. No correlation was detected
      between stress factors and colonic transit.

PMID- 9167224
TI  - Antineutrophil cytoplasm antibodies in patients with silicosis.
AB  - The presence of antineutrophil cytoplasm antibodies (ANCA) was followed up in
      silicosis with or without renal involvement. From the 68 patients with silicosis,
      5 presented renal involvement. Of these 3 showed the presence of pANCA. The other
      63 patients without renal involvement presented cANCA only in 2 cases. The
      control group showed no presence of ANCA. The incidence of ANCA in silicosis with
      renal involvement was discussed in view of an eventual elucidation of the
      pathogenesis of this disease, which was frequently associated with autoimmunity
      diseases.

PMID- 9167225
TI  - Lymph distribution of different non-steroidal anti-inflammatory drugs assessed by
      microsurgical cannulation of the thoracic duct in rat.
AB  - The motility of lymphatic vessels is regulated by arachidonate metabolites and,
      therefore, can be altered by cyclo-oxygenase blockers such as non-steroidal anti
      inflammatory drugs (NSAIDs). In order to investigate the lymphotropic properties
      of different NSAIDs, pharmacokinetics in plasma and lymph following intragastric
      administration of three model compounds, namely racemic ibuprofen, tenoxicam and
      nabumetone, were investigated in rats. Microsurgical cannulation of the thoracic
      duct allowed cumulative sampling of lymph fluid up to 48 hrs (n = 16).
      Pharmacokinetic parameters in plasma were determined in a control group (n = 12).
      Concentrations of R-, S-ibuprofen, tenoxicam, nabumetone and the metabolites OH
      ibuprofen, COOH-ibuprofen and 6-methoxy-2-naphthyl-acetic acid (6MNA, metabolite
      of nabumetone) were monitored in lymph and plasma by HPLC. To quantify the
      lymphotropic properties of the investigated compounds, a "lymphatic clearance"
      was defined by dividing the amount recovered in lymph fluid by the corresponding
      area under the plasma concentration-time curve (AUCP). The "lymphatic clearance"
      substantially differed between the investigated compounds (mean +/- SD: R
      ibuprofen 6.71 +/- 3.15 microliters/min, S-ibuprofen 3.24 +/- 1.20
      microliters/min, tenoxicam 8.74 +/- 8.11 microliters/min, nabumetone 46.05 +/-
      26.08 microliters/min and 6MNA 6.32 +/- 2.96 microliters/min). The overall
      recovery of the investigated compounds in lymph did not exceed 5% of the doses
      given. The known fact that lymphatic drainage is regulated by arachidonate
      metabolites might suggest that NSAIDs differing in their lymphotropic properties
      could result in different responses of lymphatic vessels to an inflammatory fluid
      load.

PMID- 9167226
TI  - Computerized system for assessing heart rate variability.
AB  - The principal theoretical, methodological and clinical aspects of heart rate
      variability (HRV) analysis are reviewed. This method has been developed over the
      last 10 years as a useful noninvasive method of measuring the activity of the
      autonomic nervous system. The main components and the functioning of the
      computerized rhythm-analyzer system developed by our team are presented. The
      system is able to perform short-term (maximum 20 minutes) time domain HRV
      analysis and statistical analysis of the ventricular rate in any rhythm,
      particularly in atrial fibrillation. The performances of our system are
      demonstrated by using the graphics (RR histograms, delta RR histograms, RR
      scattergrams) and the statistical parameters resulted from the processing of
      three ECG recordings. These recordings are obtained from a normal subject, from a
      patient with advanced heart failure, and from a patient with atrial fibrillation.

PMID- 9167227
TI  - Matrigel: a useful tool to study endothelial differentiation.
AB  - Matrigel is a matrix of a mouse basement membrane neoplasm. It represents a
      complex mixture of basement membrane proteins including laminin, type IV
      collagen, entactin/nitrogen and proteoheparan sulfate, but it also contains
      growth factors. Matrigel induces endothelial cells to differentiate as evidenced
      by both the morphologic changes and by the reduction in proliferation and,
      therefore, offers a convenient model to study biochemical and molecular events
      associated with angiogenesis. Further, Matrigel permits to study the roles of the
      extracellular matrix in angiogenesis.

PMID- 9167228
TI  - Diagonal earlobe crease: a coronary risk factor, a genetic marker of coronary
      heart disease, or a mere wrinkle. Ancient Greco-Roman evidence.
AB  - In a new study on the relationship between the diagonal earlobe crease (DELC),
      first described by Frank in 1973, and the presence of chronic ischemic heart
      disease, four main hypotheses are presented. Hypothesis 1: DELC is a coronary
      risk factor or a marker of coronary risk factor. Hypothesis 2: DELC is a genetic
      marker of atherosclerotic coronary disease. Hypothesis 3: DELC is, in fact, the
      result of aging and the relationship with atherosclerotic coronary disease is
      mere coincidence. Hypothesis 4: DELC is an anatomic peculiarity of the ear lobe,
      perhaps the result of a particular way of sleeping. These hypotheses are
      discussed in the light of the most important results obtained so far, in the
      literature and in the author's personal studies. Moreover, the data reported by
      Petrakis, who was the first to mention in 1980 the presence of this sign in some
      of the Greco-Roman sculptures in the museums of Rome, are corroborated by the
      observations of one of the authors, made in the Louvre Museum in Paris.

PMID- 9167229
TI  - Use of iohexol clearance to determine the glomerular filtration rate. A
      comparison between different clearance techniques in man and animal.

PMID- 9167230
TI  - Asbestos--a continuing concern.

PMID- 9167231
TI  - Surveillance and intervention studies on respiratory cancers in asbestos-exposed
      workers.
AB  - A systematic review of the literature on the surveillance of workers at presumed
      increased risk for respiratory cancer because of their exposure to asbestos
      revealed surveillance programs at the national, population, industrial, and
      factory (workplace) levels. Furthermore, 3 randomized chemoprevention trials
      involving workers exposed to asbestos were found. The nationwide programs to
      survey problems related to occupational exposure to asbestos were conducted in
      Europe. Some of the countries have policies for the surveillance of workers
      exposed either currently or formerly to asbestos. The results of the
      chemoprevention trials suggest that there are, as yet, no practical tools for
      efficient, safe chemoprevention of asbestos-induced respiratory malignancies.

PMID- 9167232
TI  - Asbestos, asbestosis, pleural plaques and lung cancer.
AB  - Inhalation of asbestos fibers increases the risk of bronchial carcinoma. It has
      been claimed that asbestosis is a necessary prerequisite for the malignancy, but
      epidemiologic studies usually do not have enough statistical strength to prove
      that asbestos-exposed patients without asbestosis are without risk. Several
      recent studies do actually indicate that there is a risk for such patients. In
      addition, case-referent studies of patients with lung cancer show an attributable
      risk for asbestos of 6% to 23%, which is much higher than the actual occurrence
      of asbestosis among these patients. Thus there is an increasing body of evidence
      that, at low exposure levels, asbestos produces a slight increase in the relative
      risk of lung cancer even in the absence of asbestosis. Consequently, all exposure
      to asbestos must be minimized.

PMID- 9167233
TI  - A meta-analysis of epidemiologic studies of lung cancer in welders.
AB  - OBJECTIVE: A meta-analysis of epidemiologic studies was carried out on lung
      cancer risk among shipyard, mild steel, and stainless steel welders, and the role
      of asbestos exposure and smoking was considered. METHODS: The meta-analysis
      consisted of calculating combined relative risks (RR) and their variances through
      a logarithm transformation of published RR values and a weighing using the
      inverted variance of each RR. RESULTS: The literature provided 18 case-referent
      and 31 cohort studies. The combined RR values were 1.38 [observed 1028, 95%
      confidence interval (95% CI) 1.29-1.48] for "all or unspecified welding
      categories", 1.30 (observed 305, 95% CI 1.14-1.48) for shipyard welders, and 1.35
      (observed 173, 95% CI 1.15-1.58) for nonshipyard welders. Similar combined RR
      values (RR) were observed for mild steel welders (combined RR 1.50, observed 137,
      95% CI 1.18-1.91) and stainless steel welders (combined RR 1.50 observed 114, 95%
      CI 1.10-2.05). No significant heterogeneity was discerned between studies of any
      welding or study design category. A marked healthy worker effect may also lead to
      an underestimation of the standardized mortality ratio for lung cancer among
      stainless steel welders. Furthermore, welders of any category are likely to be
      exposed to asbestos. Welders also seem to smoke more than the general male
      population, and therefore the hypothesis of tobacco overconsumption among welders
      could not be discarded. CONCLUSIONS: A 30-40% increase in the RR of lung cancer
      among welders cannot be explained by hexavalent chromium and nickel exposure
      among stainless steel welders. The combination of the carcinogenic effects of
      asbestos exposure and smoking may account for part of the lung cancer excess
      observed.

PMID- 9167234
TI  - Terpene exposure and respiratory effects among workers in Swedish joinery shops.
AB  - OBJECTIVES: Exposure to monoterpenes (alpha-pinene, beta-pinene and delta 3
      carene) in joinery shops was studied in Sweden during the processing of Scot's
      pine, and the acute respiratory effects among the employees were evaluated.
      METHODS: A cross-sectional study of 38 workers was carried out in 4 joinery
      shops. The investigation included personal air sampling of monoterpenes,
      biological monitoring of metabolites of alpha-pinene in the workers' urine,
      interviews following a standardized questionnaire, and dynamic spirometry.
      RESULTS: The personal exposure to monoterpenes in the joinery shops was 10-214
      mg/m3. The correlation (correlation coefficient = 0.69) between exposure to alpha
      pinene and verbenols (metabolites from alpha-pinene) in urine was relatively
      good. No acute effects on forced vital capacity or forced expiratory volume
      during 1 s were detected. The workers had significantly reduced preshift lung
      function values when compared with the values of a local reference group, even
      when smokers and ex-smokers were excluded. CONCLUSIONS: Personal exposure to the
      monoterpenes alpha-pinene, and delta 3-carene in joinery shops may exceed the
      present Swedish occupational exposure limit of 150 mg/m3 during the winter season
      when workroom air is commonly recirculated. The determination of metabolites of
      alpha-pinene (verbenols) in urine can be used as an index of exposure to fumes
      released during wood-treating processes. The results from the lung function tests
      indicate chronic rather than acute reactions in the airways. The fact that there
      were no major changes in lung function over a workshift indicates chronic
      reaction in the airways.

PMID- 9167235
TI  - Sickness absence from back pain, psychosocial work characteristics and employment
      grade among office workers.
AB  - OBJECTIVES: The relation between psychosocial work characteristics, employment
      grade, and sickness absence due to back pain was studied among office workers.
      METHODS: Base-line questionnaire data and sickness absence data collected
      continuously with a mean of 4 years of follow-up were analyzed. The subjects were
      6894 men and 3414 women aged 35 to 55 years at recruitment. The main outcome
      measures were short (< or = 7 days) and long (> 7 days) absences due to back
      pain. RESULTS: There was a strong inverse association between employment grade
      and rate of absences due to back pain (P for linear trend < 0.001); for example,
      the rate ratio for short absences among the men in a comparison of lowest versus
      highest employment grade was 8.21. The age adjusted rate ratio for the effect of
      low versus high control over work among the men was 2.22 [95% confidence interval
      (95% CI) 1.77-2.79] for short and 1.61 (95% CI 1.01-2.58) for long absences due
      to back pain. For short absences due to back pain among the men in high grades of
      employment, the rate ratio for low control was 3.42 compared with 0.78 for the
      lower grades (P for interaction < 0.001). For the women the corresponding rate
      ratios were 0.80 and 1.35, respectively (P for interaction 0.08). CONCLUSIONS:
      Absence from work due to back pain was strongly inversely related to employment
      grade. The effects of psychosocial work characteristics-particularly control
      differed by grade and gender in magnitude and direction. The psychosocial work
      environment represents a potentially reversible cause of ill health.

PMID- 9167236
TI  - Associations between self-rated psychosocial work conditions and musculoskeletal
      symptoms and signs. Stockholm MUSIC I Study Group.
AB  - OBJECTIVES: The aim was to study the associations between self-rated psychosocial
      work conditions and the characteristics and location of musculoskeletal symptoms,
      signs, and syndromes. METHODS: Perceived psychosocial work conditions were
      recorded in a cross-sectional study with 358 men and women in various
      occupations. Symptoms were recorded from the musculoskeletal system with a
      questionnaire, and signs were detected in a medical examination of all body
      regions. The analyses of statistical associations between the psychosocial
      factors and musculoskeletal disorders were performed with control for age,
      gender, and physical load. RESULTS: The most consistent and pronounced
      associations were mainly seen between poor psychosocial work conditions and
      coexisting symptoms and signs of the neck and back regions. Poor psychosocial
      work conditions were more consistently and strongly associated with signs of
      muscular (soft tissue) tenderness than with signs of tenderness in the joints,
      tendons, or muscular insertions or signs in nerve compression tests. Mainly low
      social support at work, but also high psychological demands and high job strain,
      were associated with such symptoms and signs, whereas decision latitude at work
      showed few associations with musculoskeletal disorders. CONCLUSIONS: Perceived
      poor psychosocial work conditions are statistically associated mainly with
      symptoms and signs of muscular tenderness in the central body regions. Studies on
      associations between psychosocial work conditions and musculoskeletal disorders
      should separate effect measures of different clinical signs and different body
      regions in order to avoid attenuation of the risk estimates.

PMID- 9167237
TI  - Assessing agreement between two job-exposure matrices.
AB  - OBJECTIVES: This study was undertaken to compare the operating characteristics of
      the Hoar et al job-exposure matrix and the job-exposure matrix of the National
      Occupational Hazard Survey (NOHS) of the National Institute for Occupational
      Safety and Health in the United States. Both matrices were applied to occupations
      in the metal, paper and wood, and chemical, drug and paints industries, and the
      extent of agreement between the two was estimated. METHODS: The agents (exposure
      entities) selected for the comparison were common to both matrices; altogether
      214 agents were included. For the comparison of occupations, the occupational
      codes of the Hoar et al matrix were converted to those of the NOHS-based matrix.
      For every occupational group analyzed, each of the 214 exposure entities was
      classified as to its "presence" or "absence", and a kappa statistic (kappa) was
      calculated. RESULTS: The kappa(i) ranged from 0.27 to -0.12. In general, most of
      the agreement between the 2 matrices occurred because they agreed as to the
      absence of exposure for the exposure entities. Variation in agreement was
      observed for both the individual exposure entities and for chemical families.
      CONCLUSIONS: These results indicate poor to only fair agreement between the 2 job
      exposure matrices, and they underscore the importance of understanding the rules
      for classifying exposures when any such matrix is used. Investigators also need
      to be aware of the methods and limitations of the occupational coding systems.

PMID- 9167238
TI  - Asthma in patients with farmer's lung during a five-year follow-up.
AB  - OBJECTIVES: This study assessed the incidence of asthma in patients with farmer's
      lung. METHODS: The study population consisted of 1031 patients who had
      occupational farmer's lung diagnosed from 1983 to 1988. The cases of farmer's
      lung were registered in the nationwide Register of Occupational Diseases by the
      Finnish Institute of Occupational Health, and all the patients in the study had
      received compensation from the insurance company for an occupational disease. The
      diagnosis of asthma was based on entitlement to a special refund for asthma
      medication costs from the national sickness insurance program. RESULTS: Seventy
      four cases of asthma were found among farmers with farmer's lung up to the end of
      the 5 years following the year of the diagnosis for farmer's lung. The prevalence
      of asthma was 1% in the year preceding the diagnosis. In the year of the
      diagnosis and during the 5 year of follow-up, asthma was diagnosed in an
      additional 6% of the patients. CONCLUSIONS: The results of this study confirm
      previous findings of a low prevalence of asthma before the onset of farmer's lung
      in small groups of patients. However, the results also indicate that the
      incidence of asthma increases during the first years after an episode of farmers
      lung. For example, in the present study, asthma was apparent in 7% of the
      patients 5 years after the diagnosis of farmer's lung.

PMID- 9167239
TI  - "Significant-itis"--an obsession with the P-value.

PMID- 9167240
TI  - Management 1997 of chronic obstructive pulmonary disease. Working Group of the
      Swiss Society of Pneumology.
AB  - COPD is a disorder characterized by expiratory flow limitation that does not
      change markedly over periods of several months' observation. When the diagnosis
      is suspected, COPD patients should be submitted to full assessment and initiation
      of therapy. Initial assessment includes a complete history, a detailed physical
      examination, pulmonary function tests, a chest X-ray, and blood tests. Therapy of
      COPD aims at reducing symptoms, preventing exacerbations and preserving optimal
      lung function. Many COPD patients have a bronchospastic component and usually
      show some response to bronchodilator therapy. Anticholinergics, beta 2-agonists
      or theophylline are used as monotherapy or in combination. A subgroup of patients
      with COPD may benefit from oral long-term corticosteroid therapy. At prime
      diagnosis of COPD, a trial of oral steroid under optimal bronchodilator therapy
      is warranted in order to identify steroid responders early in the course of the
      disease. Stopping smoking is the most effective preventive measure and should be
      combined with complementary approaches such as eviction of environmental
      irritants, vaccines and prescription of antioxidants. Long-term oxygen therapy is
      beneficial in chronically hypoxemic patients. Respiratory rehabilitation uses a
      multidisciplinary approach aiming at decreasing dyspnea, increasing exercise
      tolerance and improving quality of life. Nocturnal home noninvasive mechanical
      ventilatory assistance can improve arterial blood gas tensions in patients with
      respiratory failure, but the long-term effect on survival is still under
      investigation. In selected patients, surgery (bullectomy, lung volume reduction,
      lung transplantation) may greatly improve pulmonary function.

PMID- 9167241
TI  - Serological serum protein fraction and responses to Brucella melitensis in lambs
      fed aflatoxins.
AB  - Twenty-four lambs were given 2 ppm aflatoxins (AF) in their diet for 37 d and 12
      were kept as a control group. After this time, toxic feed was removed for a
      further 35 days (clearance period). On day 17 all lambs were vaccinated with B
      melitensis strain Rev-1, and blood samples were taken regularly to determine the
      levels of antibodies and serum proteins. Aflatoxins decreased titers of Rose
      Bengal test and optical densities of ELISA, both in the intoxicated and clearance
      periods. Complement fixation titers were lower in intoxicated lambs, except on
      the 23rd day of intoxication, but not statistically different (P > 0.05). No
      effect of AF was noted on total serum proteins, but albumin and alfa-globulin
      levels were lower for intoxicated lambs than for the control group. Beta-globulin
      concentration did not change, and increases in gamma-globulins levels in dosed
      lambs were observed throughout the experiment. These results suggest that AF
      causes a failure in the acquired immunity system of lambs by decreasing antibody
      production and altering serum profile proteins.

PMID- 9167242
TI  - In vivo and in vitro effect of sulfamethazine on hepatic mixed function oxidases
      in rats.
AB  - Sulfamethazine (SMZ) administration (ip, 3 d) of different doses to adult male
      rats showed significant increases in the electron transport components and
      activities of aminopyrine N-demethylase and aniline hydroxylase at the the 150 mg
      SMZ/kg dose level. However, 300 mg SMZ/kg doses produced a significant decrease
      in cytochrome P-450 and the activity of aminopyrine N-demethylase. In a longer
      duration study, 300 mg SMZ/kg caused significant decreases in cytochrome P-450
      and in the activity of aminopyrine N-demethylase. The inducer dose of 150 mg
      SMZ/kg and the inhibitory dose of 300 mg SMZ/kg were selected for dosing young
      male, old male and adult female rats. Sulfamethazine administration to young male
      rats resulted in a significant induction of electron transport components and
      drug metabolizing enzymes at both dose levels. However, SMZ treatment of old rats
      produced significant decreases in electron transport components and aminopryine N
      demethylase activity at both dose levels. A significant induction in the levels
      of electron transport components was observed with 150 mg SMZ/kg in female rats.
      All other parameters were unchanged. Sulfamethazine resulted in a mixed type of
      inhibition (Ki = 3.5 mM) of aminopyrine N-demethylase in vitro. Hydroxylated
      metabolites destructed the spectral and catalytic activity of cytochrome P-450.
      Our studies suggest that SMZ is a substrate of the mixed function oxidase system
      and induction is dependent on dosage, age and sex of the animals.

PMID- 9167243
TI  - The oral and intratracheal toxicities of ROUNDUP and its components to rats.
AB  - The toxicities of ROUNDUP and its component chemicals, glyphosate (N
      phosphonomethylglycine) and polyoxyethyleneamine (POEA), were determined at 0, 1,
      3, 6 and 24 h following administration to rats. The intratracheal administration
      of glyphosate (0.2 g/kg), POEA (0.1 g/kg), a mixture of glyphosate (0.2 g/kg) +
      POEA (0.1 g/kg), or ROUNDUP (containing 0.2 g/kg glyphosate and 0.1 g/kg POEA)
      elicited immediate respiratory effects which were more severe and which lasted
      longer in the groups receiving the POEA-containing preparations than in the
      glyphosate alone group. By 1 h, all test preparations had caused deaths, but more
      occurred from the POEA-containing preparations than from glyphosate. The po
      administration of POEA (1 g/kg), the mixture of glyphosate (2 g/kg) +POEA (1
      g/kg), or ROUNDUP (containing 2 g/kg glyphosate and 1 g/kg POEA) produced
      diarrhea and blood-stained weeping from noses. Death was only seen from POEA at
      24 h. Glyphosate (2 g/kg po) produced transient diarrhea without nose bleeds;
      POEA caused diarrhea at 1 h; and the mixture of POEA + glyphosate produced
      diarrhea later that increased in severity with time. Bloody nose secretions were
      seen only with the preparations that contained POEA. No deaths, respiratory
      effects or bloody nose secretions occurred in controls given saline. Both POEA
      and glyphosate caused lung hemorrhages and lung epithelial cell damage with po or
      intratracheal exposures. These results indicate POEA and preparations that
      contained POEA were more toxic than glyphosate.

PMID- 9167244
TI  - Hydrogen sulfide poisoning: an antidotal role for sodium nitrite?
AB  - In 2 separate incidents, 6 patients were poisoned with hydrogen sulfide (H2S) in
      sewer gas. In the first incident, mixing acid- and sodium hydroxide-based drain
      cleaners in a confined space resulted in 4 poisonings and 2 deaths. Three would
      be rescuers were seriously poisoned and 1 died. Two survivors had neurological
      sequelae. Sodium nitrite appeared to have some clinical efficacy in 1 case. The
      second incident involved 2 patients working on a pump in a sewage pond. A patient
      lying on a raft close to the pond surface was seriously poisoned; sodium nitrite
      was clinically efficacious and this patient survived without developing
      neurological sequelae. Sodium nitrite deserves further clinical study as a
      potential H2S antidote.

PMID- 9167245
TI  - Acute intoxication and recovery following massive turpentine ingestion: clinical
      and toxicological data.
AB  - Reports of acute turpentine intoxication, particularly containing toxicological
      data, are poorly verified in the literature. This report regards the intentional
      massive ingestion of turpentine solution in an elderly woman who developed mainly
      central nervous system manifestations, then had an impressive and quick total
      recovery although the initial prognosis was very bad. Blood and urine levels of
      turpentine were monitored using gas chromatography and at the early toxicogenic
      stage were 28 micrograms/mL and 15 micrograms/mL respectively. Gastric fluid
      analysis on admission to the hospital revealed the presence of approximately 200
      mL turpentine in the intestine. A review of earlier reports is given.

PMID- 9167246
TI  - Naproxen toxicosis in a puppy.
AB  - Naproxen toxicosis is described in a puppy that had been given 220 mg of naproxen
      (ALLEVE) over a 4-d period. Clinical signs included melena, lethargy and
      vomiting. The puppy recovered with a blood transfusion (due to anemia),
      gastroprotective medications, and supportive care.

PMID- 9167247
TI  - Ammonia pipeline rupture: risk assessment to cattle.

PMID- 9167248
TI  - Public health impact on drug residues in animal tissues.
AB  - Consumers have expressed concern regarding the health impact of drug residues in
      their food. Animal residues in animal tissues above the legal tolerance clearly
      have an impact on human health. Tolerances represent the maximal level or
      concentration of antimicrobial residues permitted in animal tissues at the time
      of slaughter. The tolerances are intended to ensure that residual drugs will have
      no harmful effects if ingested. This paper describes the existing evidence for
      specific health hazards for certain pharmacological classes of drugs and explains
      the risks associated with drug residues in meat and poultry above the established
      tolerance. The primary focus is on possible public health consequences that may
      occur as a result of acute exposure to illegal residues. In addition, long-term
      effects are discussed with added comments about the effect of residues on the
      intestinal flora. Most residues of veterinary drugs occur in food at such low
      levels that they rarely pose a chronic or long-term health hazard to consumers.
      The importance of food safety through the reduction of residues in our food
      supply cannot be overemphasized. Food safety remains a major challenge
      confronting contemporary society.

PMID- 9167249
TI  - Poisons and panic!
AB  - Home management of the majority of poison center callers is safe and cost
      effective; but in the absence of poison center consultation, could callers
      correctly assess the severity of a poisoning? This study was conducted to
      determine indirectly whether callers can correctly assess the toxicity of a
      substance involved in a poison exposure by determining whether caller panic
      levels correlated with the expected toxicity of the exposure. Using a digital
      call recorder, 100 calls to the National Capital Poison Center involving children
      < 10 y were reviewed. The panic level of each caller was assessed and scored on a
      4-point rating scale and, compared to the toxicity of the substance implicated
      (also on a 4-point rating scale). Most callers were mothers (85%), most patients
      were < 4 y (86%), and most exposure routes were ingestions (89%). Although there
      were only 12 male callers, male callers were significantly more panicked than
      females. Overall, there was a correlation between the panic level of the poison
      center callers and the toxicity of the substance involved in the exposure, with
      the mean panic level increasing as the toxicity increased. However, only 36% of
      patients had a panic level that was exactly appropriate for the toxicity level.
      Most callers were more panicked than they needed to be (57%), including 14% of
      callers who were much more panicked than they needed to be. Seven percent of
      callers were too calm; they appeared not to understand how toxic the exposure
      really was. Based on these data, one could predict that the majority of callers
      were sufficiently panicked that, had the poison center not been available to
      provide immediate consultation, the callers may have over-reacted and called 911
      or gone straight to a hospital. Yet only 1 of the 57 overly-panicked callers was
      calling about a patient who actually required medical intervention. Of great
      concern, the 7% of patients who were too calm may have required medical
      intervention that, due to underestimation of the severity of the exposure, may
      have been withheld or delayed. Three of these "too calm" cases actually required
      medical intervention. Although subject to a number of design limitations, this
      study suggests that callers frequently over-react to poison exposures. In the
      absence of a well-utilized poison control system, excessive panic may contribute
      to excessive use of emergency departments and ambulance services and create
      excessive health care costs for poisoning emergencies.

PMID- 9167250
TI  - Assessment of learning by emergency medicine residents and pharmacy students
      participating in a poison center clerkship.
AB  - An AAPCC-designated poison center developed and validated an objective testing
      instrument to evaluate learning during a poison center clinical rotation for 2nd
      year emergency medicine residents and 5th-year pharmacy students. The examination
      contained multiple-choice, true-false, and fill-in questions pertaining to basic
      clinical toxicology. A pretest was administered prior to the rotation and a post
      test was administered upon completion of the rotation. Overall pre-test mean was
      56.2%; physician pre-test mean was 73.8%, and student pre-test mean was 43.9%.
      Overall post-test mean was 78.7%; physician post-test mean was 85.7%, and student
      post-test mean was 81%. Pre-test scores ranged from 21 to 86% for the group, and
      post-test scores ranged from 68 to 96%. The mean difference in pre-test to post
      test score was 26.9%. These data suggest that a poison center rotation can result
      in significant increases in post-test scores in comparison to pre-test scores.

PMID- 9167251
TI  - Implementation of self-scheduling in the poison center.
AB  - Self-scheduling was introduced to our Poison Control Center (PCC) as an
      alternative method of scheduling. The traditional method of scheduling was
      becoming an overwhelming task for the managing director, and the specialists'
      individual needs were not adequately met. Therefore, self-scheduling was
      implemented to meet the needs of the PCC as well as create the feelings of
      empowerment and autonomy for the specialists. The staff was educated on the
      process of self-scheduling. This process involved assessing, planning,
      implementing and evaluating. Using the democratic process, guidelines were
      established for shift hours, shift rotation, weekends, vacation and holidays. The
      plan included assigning a specialist as "schedule mediator". The mediator was
      responsible for assessing the schedule for any over- or under-staffing and
      negotiating schedule changes between the specialists. When the schedule's gaps
      had been negotiated, the completed schedule was posted. Finally, the staff
      completed a questionnaire to evaluate self-scheduling. All of the specialists
      strongly agreed that there had been a positive outcome from implementing self
      scheduling. Their comments included "enjoyed the flexibility in doing her own
      schedule" and "enjoyed the participating in the operation of the PCC".

PMID- 9167252
TI  - An investigation of household product labels in Turkey.
AB  - One hundred ninety-nine household product labels were evaluated for Turkish
      marking and labeling requirements and the adequacy for management of high dose
      exposures. Fifty-six percent of the products were proper. The rest had inadequate
      information or did not have warning instructions, an ingredients list and/or
      other requirements. The requirements do not provide adequate consumer warning and
      management of overdose ingestions. Household product labeling standards on Turkey
      should be reviewed and improved by collaboration with poison centers and
      manufacturers.

PMID- 9167253
TI  - Bentonite toxicosis in a cat from cat litter?

PMID- 9167254
TI  - Anatomical aspects for surgery within the floor of the IVth ventricle.
AB  - Successful removal of brainstem lesions is among other factors dependent on a
      safe surgical approach into the brainstem avoiding functional morbidity of
      superficially located nervous structures. Most midline pontine and pontomedullary
      lesions can be reached via a transvermian approach through the rhomboid fossa.
      This review describes the anatomical basis for the pericollicular paramedian
      surgical approaches into the rhomboid fossa with special emphasis on the
      microscopic anatomy.

PMID- 9167255
TI  - Coxiella burnetii: the 'query' fever bacterium. A model of immune subversion by a
      strictly intracellular microorganism.
AB  - Although substantial progress occurred in the knowledge of Coxiella burnetii
      during the past years, the pathophysiology of Q fever is still obscure. Emerging
      evidence from clinical investigations suggested that certain disorders of cell
      mediated immunity play a pivotal role in Q fever and especially in its chronic
      form. This review analyses the potential strategies that C. burnetii, a strictly
      intracellular pathogen, use to divert microbicidal mechanisms of macrophages and
      to depress protective T-cell mediated immunity. The role of monocytes in the
      induction of Q fever is specifically discussed.

PMID- 9167256
TI  - Physiology and genetics of the dimorphic fungus Yarrowia lipolytica.
AB  - The ascomycetous yeast Yarrowia lipolytica (formerly Candida, Endomycopsis, or
      Saccharomyces lipolytica) is one of the more intensively studied 'non
      conventional' yeast species. This yeast is quite different from the well-studied
      yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe with respect to its
      phylogenetic evolution, physiology, genetics, and molecular biology. However, Y.
      lipolytica is not only of interest for fundamental research, but also for
      biotechnological applications. It secretes several metabolites in large amounts
      (i.e. organic acids, extracellular proteins) and the tools are available for
      overproduction and secretion of foreign proteins. This review presents a
      comprehensive overview on the available data on physiology, cell biology,
      molecular biology and genetics of Y. lipolytica.

PMID- 9167257
TI  - Distribution, diversity and evolution of the bacterial mercury resistance (mer)
      operon.
AB  - Mercury and its compounds are distributed widely across the earth. Many of the
      chemical forms of mercury are toxic to all living organisms. However, bacteria
      have evolved mechanisms of resistance to several of these different chemical
      forms, and play a major role in the global cycling of mercury in the natural
      environment. Five mechanisms of resistance to mercury compounds have been
      identified, of which resistance to inorganic mercury (HgR) is the best
      understood, both in terms of the mechanisms of resistance to mercury and of
      resistance to heavy metals in general. Resistance to inorganic mercury is encoded
      by the genes of the mer operon, and can be located on transposons, plasmids and
      the bacterial chromosome. Such systems have a worldwide geographical
      distribution, and furthermore, are found across a wide range of both Gram
      negative and Gram-positive bacteria from both natural and clinical environments.
      The presence of mer genes in bacteria from sediment cores suggest that mer is an
      ancient system. Analysis of DNA sequences from mer operons and genes has revealed
      genetic variation both in operon structure and between individual genes from
      different mer operons, whilst analysis of bacteria which are sensitive to
      inorganic mercury has identified a number of vestigial non-functional operons. It
      is hypothesised that mer, due to its ubiquity with respect to geographical
      location, environment and species range, is an ancient system, and that ancient
      bacteria carried genes conferring resistance to mercury in response to increased
      levels of mercury in natural environments, perhaps resulting from volcanic
      activity. Models for the evolution of both a basic mer operon and for the Tn21
      related family of mer operons and transposons are suggested. The study of
      evolution in bacteria has recently become dominated by the generation of
      phylogenies based on 16S rRNA genes. However, it is important not to
      underestimate the roles of horizontal gene transfer and recombinational events in
      evolution. In this respect mer is a suitable system for evaluating phylogenetic
      methods which incorporate the effects of horizontal gene transfer. In addition,
      the mer operon provides a model system in the study of environmental microbiology
      which is useful both as an example of a genotype which is responsive to
      environmental pressures and as a generic tool for the development of new
      methodology for the analysis of bacterial communities in natural environments.

PMID- 9167258
TI  - Botulinum toxin: the story of its development for the treatment of human disease.

PMID- 9167259
TI  - Looking ahead: some genetic issues of the future.

PMID- 9167260
TI  - The Olmec heart effigy: earliest image of the human heart.

PMID- 9167261
TI  - Microbial secondary metabolites play important roles in medicine; prospects for
      discovery of new drugs.

PMID- 9167262
TI  - Cortisone therapy: a challenge to academic medicine in 1949-1952.

PMID- 9167263
TI  - Individual interests, societal interests, and reproductive technologies.

PMID- 9167264
TI  - Environmental contamination and seasonal variation of metals in soils, plants and
      waters in the paddy fields around a Pb-Zn mine in Korea.
AB  - The objective of this study is to investigate the extent and degree of heavy
      metal contamination of paddy fields influenced by metalliferous mining activity.
      Paddy soils, rice plants and irrigation waters were sampled along six traverse
      lines in the vicinity of the mine and nearby control site. Soil samples were
      taken 30, 80 and 150 days after rice transplanting, to study seasonal variation
      of their chemical properties and heavy metal concentrations. Sampling of rice
      plants and irrigation waters was also undertaken with seasons. The analysis of
      the samples were carried out using ICP-AES for 25 elements including Cd, Cu, Pb
      and Zn. Physical and chemical properties of soils (pH, loss-on-ignition, cation
      exchange capacity and texture) and waters (pH, Eh and temperature) were also
      measured. The properties of soils were similar to the average Korean soils, with
      the exception of some samples taken in the vicinity of the mine. Concentrations
      of Cd, Cu, Pb and Zn in paddy soils, rice plants and irrigation waters sampled in
      the immediate vicinity of the mine were relatively high due to the seepage of
      metals from mining dump sites. Although there was variation between sampling
      sites, soil pH values under reducing conditions were on average higher than those
      under oxidising conditions. Relatively low content of organic matter and low
      cation exchange capacity of soils were found at 80 days after rice transplanting
      (P < 0.05). No seasonal variations in metal concentrations were found in paddy
      soils throughout the period of the rice growing, in which soils ranged from
      flooded reducing conditions through most of the growing season to drained
      oxidising conditions before and at harvest. Relatively high metal concentrations
      were found in the rice stalks and leaves under oxidising conditions. The
      sequential extraction analysis of selected soil samples confirmed that high
      proportions of exchangeable fractions of the metals were found under oxidising
      conditions. It was shown that Cd and Zn concentrations in rice leaves and stalks
      and rice grain increased with increasing metal concentrations in paddy soils to a
      greater extent than for Cu and Pb. This difference in uptake is in agreement with
      the greater proportions of Cd and Zn, compared with Cu and Pb, in the
      exchangeable soil fraction extracted with MgCl2. Average daily intake from
      locally grown rice by the residents was estimated to be 121 micrograms Cd and 126
      micrograms Pb. Thus, long-term metal exposure by regular consumption of the rice
      poses potential health problems to residents in the vicinity of the mine,
      although no adverse health effects have as yet been observed.

PMID- 9167265
TI  - Estimation of heavy metal transformations in municipal solid waste.
AB  - The behaviour of heavy metals bound to municipal solid waste (MSW) and exposed to
      2 decades of anaerobic waste stabilization processes have been estimated. Heavy
      metal solid forms in a waste degradation residue have been compared with a
      reconstructed waste similar to that initially disposed of in 1973. The initial
      waste was composed of a mixture of shredded MSW (95% dry wt.) and anaerobic
      sewage sludge (5% dry wt.). A sequential chemical extraction method has been used
      to fractionate the heavy metals into five categories of available and reactive
      solid forms. The results imply that these forms can be ascribed to approximately
      30% of the total content of the heavy metals in the degraded waste and the
      portion of heavy metals bound to oxidizable solid forms seems to be higher in the
      degraded than the fresh MSW. The bulk of the remaining heavy metals are assumed
      to be less available and bound into resistant lattice structures, such as metal
      and polymer items. A comparison between fractionation patterns of the waste in
      this study and of a few sediments collected from different environments imply
      similarities between the fresh MSW and an oxic sediment from one site and the
      sewage sludge and anoxic sediments from another site. Fractionation patterns of
      the degraded waste are found to be quite similar to those of the anoxic
      sediments, except for Pb, Ni and Cd which are more similar to fresh MSW.

PMID- 9167266
TI  - Normotensive blood pressure in mice with a disrupted renin Ren-1d gene.
AB  - Renin is an aspartyl protease that is involved in the conversion of
      angiotensinogen to angitensin II and hence participates in the regulation of
      blood pressure. Mice are polymorphic for the number of renin genes with some
      strains harbouring two renin genes, Ren-1d and Ren-2. To study the role of renin
      Ren-1d in regulating cardiovascular homeostasis, mice with a disrupted Ren-1d
      gene were created. Analyses of kidney renin mRNA expression in Ren-1d-/-/Ren-2+/+
      mice demonstrated that only Ren-2 transcripts were present. Mean arterial blood
      pressures of Ren-1d+/+/Ren-2+/+, Ren-1d+/-/Ren-2+/+ and Ren-1d-/-/Ren-2+/+ mice
      showed no significant differences. These observations demonstrate that the Ren-1d
      gene product is not essential for normal blood pressure maintenance under normal
      physiological conditions.

PMID- 9167267
TI  - Germ-free and barrier-raised TGF beta 1-deficient mice have similar inflammatory
      lesions.
AB  - Barrier-raised transforming growth factor beta 1 (TGF beta 1)-deficient mice
      consistently die before 35 days of age of a severe multiorgan inflammatory
      disease that can affect the skeletal muscle, heart, liver, pancreas, salivary
      gland, lung, oesophagus and stomach. The underlying cause of this disease is not
      known. To determine whether abnormal responsiveness of the immune system to the
      presence of enteric flora plays a causative role, a colony of TGF beta 1
      deficient and wild-type mice were raised in a sterile environment. Seven germ
      free TGF beta 1-deficient and 5 germ-free TGF beta 1 wild-type mice were
      examined. Lesion development was analysed and compared with historical data on 50
      barrier-raised TGF beta 1 mutant mice and 32 barrier-raised wild-type mice. All
      germ-free TGF beta 1-deficient mice died shortly after weaning, as do their
      barrier-raised counterparts. There was a significant delay in death in germ-free
      TGF beta 1-deficient mice compared with barrier-raised mutant mice. However,
      there was no difference in the type, severity or incidence of lesions between TGF
      beta 1 mutant mice raised under germ-free or barrier conditions. Germ-free wild
      type mice had no lesions. It is concluded that microorganisms play a minimal role
      in disease induction in TGF beta 1-deficient mice.

PMID- 9167268
TI  - Phenotypic and genotypic stability of multiple lines of transgenic pigs
      expressing recombinant human protein C.
AB  - The genotypic and phenotypic stability of four lines of transgenic pigs
      expressing recombinant human protein C in milk was examined. Two lines were
      established with a construct consisting of a 2.6 kb mouse WAP promoter and a 9.4
      kb human protein C genomic DNA. Two lines were established with another construct
      consisting of a 4.1 kb mouse WAP promoter and a 9.4 kb human protein C genomic
      DNA. Genotypic stability was measured by transgene copy number transmission.
      Outbred offspring having a single transgene integration locus were established
      from a founder having three independent, multicopy loci. Phenotypic stability
      over multiple lactations was defined by the combination of recombinant human
      protein C expression levels and the isoform signature of recombinant human
      protein C in western blots. Both cDNA and genomic human protein C transgenes gave
      similar ranges of expression levels of about 100-1800 micrograms ml-1. Within a
      given outbred lineage having a single loci for the cDNA transgene, the expression
      levels ranged between 100-400 micrograms ml-1. Western blots of reduced
      recombinant protein C revealed that single chain content was not dependent on
      expression level and was consistent within each transgenic line, but varied
      between transgenic lines. This suggests that native swine genetics may play a
      role in selection of production herds with optimal post-translational proteolytic
      processing capability. Although swine are not conventional dairy livestock, it is
      agreed that the short generation times, multiple offspring per litter, stable
      paternal transmission of the transgene, and milk production capabilities of swine
      offer distinct advantages over conventional dairy livestock for the establishment
      of a herd producing a therapeutic recombinant protein.

PMID- 9167269
TI  - Actions and interactions of growth hormone and insulin-like growth factor-II:
      body and organ growth of transgenic mice.
AB  - To characterize long-term actions and interactions of growth hormone (GH) and
      insulin-like growth factor-II (IGF-II) on postnatal body and organ growth,
      hemizygous phosphoenolpyruvate carboxykinase (PEPCK)-human IGF-II transgenic mice
      were crossed with hemizygous PEPCK-bovine GH transgenic mice. The latter are
      characterized by two-fold increased serum levels of IGF-I and exhibit markedly
      increased body, skeletal and organ growth. Four different genetic groups were
      obtained: mice harbouring the IGF-II transgene (I), the bGH transgene (B), or
      both transgenes (IB), and non-transgenic controls (C). These groups of mice have
      previously been studied for circulating IGF-I levels (Wolf et al., 1995a),
      whereas the present study deals with body and organ growth. Growth curves (week 3
      to 12) were estimated by regression with linear and quadratic components of age
      on body weight and exhibited significantly (p < 0.001) greater linear
      coefficients in B and IB than in I and C mice. The linear coefficients of male I
      and C mice were significantly (p < 0.001) greater than those of their female
      counterparts, whereas this sex-related difference was absent in the bGH
      transgenic groups. The weights of internal organs as well as the weights of
      abdominal fat, skin and carcass were recorded from 3.5- to 8-month-old mice. In
      addition, organ weight-to-body weight-ratios (relative organ weights) were
      calculated. Except for the weight of abdominal fat, absolute organ weights were
      as a rule significantly greater in B and IB than in I and C mice. IGF-II
      overproduction as a tendency increased the weights of kidneys, adrenal glands,
      pancreas and uterus both in the absence and presence of the bGH transgene.
      Analysis of relative organ weights demonstrated significant (p < 0.05) effects of
      elevated IGF-II on the relative growth of kidneys (males and females) and adrenal
      glands (females), confirming our previous report on organ growth of PEPCK-IGF-II
      transgenic mice. In females, IGF-II and GH overproduction were additive in
      stimulating the growth of spleen and uterus, providing evidence for tissue
      specific postnatal growth promoting effects by IGF-II in the presence of elevated
      IGF-I.

PMID- 9167270
TI  - A comparison of the germline potential of differently aged ES cell lines and
      their transfected descendants.
AB  - The germline transmission (g.l.t.) of gene trap or gene targeted mutations by ES
      cell-derived chimaeric mice is a crucial step in the generation of stable
      transgenic lines. The wild-type ES cell lines CJ7, D3 and R1 of different passage
      numbers and their transfected clone-descendants generated in gene targeting or
      gene trap experiments were tested for their ability to colonize the germline. The
      maximal g.l.t. age for wild-type ES cells was equal to passage 26 and for
      transfected clones was equivalent to passage 32 of parental lines. It is shown
      that wild-type ES cells of less than a passage 15 should be used for effective
      production of transgenic g.l.t. clones. A simple system is outlined to evaluate
      the probability of g.l.t. on the basis of the chimaeric progeny obtained.

PMID- 9167271
TI  - UDP-glucose: flavonol 7-O-glucosyltransferase activity in flower extracts of
      Chrysanthemum segetum.
AB  - The yellow colour of Chrysanthemum segetum petals is due to the presence of the 7
      O-glucosides of quercetin and particularly gossypetin (8-hydroxyquercetin). In
      petal extracts of C. segetum an enzyme was demonstrated which catalyzes the
      transfer of the glucosyl moiety of uridine 5'-diphosphoglucose (UDPG) to the 7
      hydroxyl group of flavonols with gossypetin and quercetin as the best substrates.
      Besides flavonols flavanones and flavones were found to be glucosylated in the 7
      position. The pH-optimum of the reaction highly depended on the substrate used.
      With quercetin as substrate, maximal enzyme activity occurred at a pH of 8.25 and
      a temperature of 25 degrees C, but 7-O-glucosylation also proceeded at low
      temperatures. Studies on temperature stability revealed, that there was no
      influence on the glucosylation reaction up to 40 degrees C. Higher temperatures
      led to a loss of enzyme activity. Using gossypetin as a substrate a similar
      course of temperature stability was observed. Addition of Mg2+, Ca2+ and KCN
      slightly stimulated 7-O-glucosylation, whereas Co2+, Cu2+, Fe2+, Hg2+, p
      hydroxymercuribenzoate and N-ethylmaleimide showed a strong inhibitory effect.
      Additional enzymatic studies were performed with the commercial strain "Stern des
      Orients" where gossypetin 7-O-glucoside is restricted to the inner parts of the
      petals. For enzyme extracts from both parts of the petals gossypetin was found to
      be the most attractive substrate. In comparison to quercetin (133.4 mu kat/kg
      protein) an about three times higher specific activity of the 7-O
      glucosyltransferase(s) was determined with gossypetin (382.1 mu kat/kg protein)
      as substrate, indicating that hydroxylation of quercetin in 8-position to
      gossypetin precedes 7-O-glucosylation.

PMID- 9167272
TI  - Some properties of spectrin-like proteins from Pisum sativum.
AB  - Proteins cross-reacting with antibodies directed against alpha- and beta-spectrin
      were recently detected in plant cells. In this report we have studied the ability
      of these proteins to interact with other components of membrane skeleton such as
      ankyrin, f-actin and calmodulin. It was found that the polypeptide of high
      molecular weight reacting with anti-alpha-spectrin antibody binds calmodulin in
      Ca(2+)-dependent manner. Protein complexes containing polypeptides cross-reacting
      with anti-spectrin antibodies interact with muscle f-actin (in co-sedimentation
      assay) and with erythrocyte ankyrin (ELISA-type assay). These data further
      substantiate a possibility of occurrence of spectrin-based membrane skeleton in
      higher plant cells.

PMID- 9167273
TI  - Characterization and cloning of cutinase from Ascochyta rabiei.
AB  - Ascochyta rabiei, the causal agent of Ascochyta blight on chickpea plants,
      secretes a cutinase in the culture filtrate when it is induced by cutin or
      hydroxylated fatty acids. This cutinase is the main esterase in the culture
      fluids. The enzyme was purified to homogeneity by three successive
      chromatographic steps. It showed an apparent molecular weight of 22 kD in SDS
      PAGE and cleaved ester bonds of 3H-labelled cutin or p-nitrophenylbutyrate with
      maximal activities around pH 8. As a serine esterase, cutinase is strongly
      inhibited by organophosphorous compounds and the most effective inhibitor 2,3,5
      trichloropyridine-6-(O-methyl-O-n-butyl)-phosphateester++ + (MAT 9564) shows a Ki
      value of 0.8 nM. The cutinase gene was cloned from a genomic cosmid library by
      screening with two oligonucleotides directed against cutinase consensus peptides.
      The gene was subcloned to a 1.7 Kb SaII/HindIII-insert and sequenced. The
      cutinase gene codes for a 223 amino acid protein with strong homology to other
      fungal cutinase sequences. The purified cutinase is encoded by a single copy
      gene.

PMID- 9167274
TI  - Isolation and analysis of moenomycin and its biosynthetic intermediates from
      Streptomyces ghanaensis (ATCC 14672) wildtype and selected mutants.
AB  - Streptomyces ghanaensis (ATCC 14672) produces the phosphoglycolipid antibiotic
      moenomycin consisting of several components. A solid phase extraction procedure
      was developed which allowed a rapid isolation of both moenomycin and its
      biosynthetic intermediates from culture filtrates. Semi-preparative high
      performance liquid chromatography followed by high performance liquid
      chromatography-mass spectrometry provided structural data on the different
      moenomycin components. In order to obtain initial information on the biosynthetic
      pathway, moenomycin non-producing mutants were isolated. They were shown to
      release intermediates with shorter lipid chains suggesting that the lipid chain
      synthesis probably takes place at a later stage of the moenomycin biosynthesis.
      Based on the biological activity and the analytical data, we assume that a
      modification and in particular a shorter lipid portion drastically influences the
      inhibitory activity of this antibiotic.

PMID- 9167276
TI  - Mechanism of free and conjugated neocarzinostatin activity: studies on
      chromophore and protein uptake using a transferrin-neocarzinostatin conjugate.
AB  - Targeting studies using the anti-cancer agent neocarzinostatin (NCS), conjugated
      to anti-bodies have shown relatively poor specificity. From the literature, it is
      unclear whether NCS mediates its effects either in conjugated or unconjugated
      form. In the present work we have used a conjugate of NCS with transferrin, a
      biological ligand with a well defined endocytic route, to probe these mechanisms.
      NCS was covalently coupled to transferrin using the heterobifunctional reagent
      sulfo-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC) and 2-iminothiolane
      to give a stable thioether-linked conjugate with a ratio of 1.6 mol of NCS per
      mole of transferrin. The binding activity of transferrin was completely retained.
      Conjugation of NCS to transferrin resulted in an apparent enhancement of
      cytotoxicity. However, incubation with excess transferrin had no influence on the
      observed enhanced toxicity, indicating that endocytosis is not responsible.
      Further experiments demonstrated that the apparent enhancement was dependent on
      incubation conditions and not an effect due to endocytosis of ligand. Studies
      where apo-NCS competed with holo-NCS and transferrin strongly indicated that the
      cytotoxicity of both NCS and conjugate is mediated by direct entry of the
      dissociated chromophore into the cell.

PMID- 9167275
TI  - Structure-cytotoxicity relationships of a series of natural and semi-synthetic
      simple coumarins as assessed in two human tumour cell lines.
AB  - The cytotoxicity of 22 natural and semi-synthetic simple coumarins was evaluated
      in GLC4, a human small cell lung carcinoma cell line, and in COLO 320, a human
      colorectal cancer cell line, using the microculture tetrazolium (MTT) assay. With
      IC50 values > 100 microM, following a continuous (96 h) incubation, most
      coumarins exhibited only low cytotoxicity. Several compounds, however, displayed
      significant potencies. As far as the structure--cytotoxicity relationship is
      concerned, it is conspicuous that all the potentially active natural compounds
      possess at least two phenolic groups in either the 6,7- or 6,8-positions. In
      addition, the 5-formyl-6-hydroxy substituted semi-synthetic analogue was found to
      be potent, reflecting the importance of at least two polar functions for high
      cytotoxicity.

PMID- 9167277
TI  - Biotyping of Campylobacter strains isolated in Lagos, Nigeria using the modified
      Preston biotype.
AB  - Fifty-eight Compylobacter strains were isolated from children with diarrhoea at
      various health centres in Lagos and from healthy chicken. Twenty-nine strains of
      Campylobacter were isolated from humans, while the same number were isolated from
      chicken. The strains were biotyped using the modified Preston biotype scheme. The
      Preston biotyping results have been compared with the results of Penner
      serotyping. Out of fifty-eight strains studied, the technique identified ten
      strains (17%) as C. coli, three (5%) as C. lari and fourty-five (78%) as C.
      jejuni, by the coding system. This technique identified twenty-eight
      Campylobacter species. This method highlights the usefulness of this technique in
      the biotyping of local strains, however, when the two schemes are used in
      combination they give excellent typing results suitable for epidemiological
      purposes.

PMID- 9167278
TI  - Triterpenoids from Acaena pinnatifida R. et P.
AB  - Eight urs-12-ene triterpenoids, beta-sitosterol, (+)-catechin, and apigenin 7-O
      glucoside were isolated from the leaves of Acaena pinnatifida R. et P. The
      triterpenoids were characterized as pomolic acid, pomolic acid-3-acetate,
      tormentic acid, 2-epi-tormentic acid, euscaphic acid, tormentic acid glucoside,
      niga-ichigoside F1, and niga-ichigoside F2.

PMID- 9167279
TI  - Definition of essential amino acid residues in the recognition of a peptide by a
      mouse monoclonal antibody.
AB  - A mouse monoclonal antibody reacting in ELISA with a synthetic peptide
      representing a linear amino acid stretch of the protein antigen was tested on all
      overlapping 5-mer to 9-mer fragments of the peptide, as prepared by multi-pin
      synthesis. Analysis of the binding data suggests that several residues in the
      peptide might be relatively unrelevant for recognition, while few others seem to
      play a critical role as key residues. On the basis of such observations, we
      attempted to reconstruct an alternative essential epitope by introducing multiple
      amino acid substitutions in the 9-mer peptide exhibiting the best binding
      activity, and then tested its ability to be recognized by the monoclonal
      antibody.

PMID- 9167280
TI  - Additional sulfur compounds from the anal glands of the striped polecat, Ictonyx
      striatus (Mustelidae, Mammalia).
AB  - Two sulfur compounds have been identified in the anal gland secretions of captive
      raised adults of the striped polecat (Ictonyx striatus), an African mustelid. 3
      Ethyl-1,2-pentanedithiolane was observed in the secretions of an adult male and
      an adult female. 1,3-Pentanedithiol was observed in the male; this compound has
      not previously been reported from mustelid anal glands.

PMID- 9167281
TI  - Health, Society and Alcohol.
AB  - The European Conference, Health, Society and Alcohol held in Paris, 12-14
      December 1995, was a meeting point between science and policy. Science informed
      the policy process. As a tool for policy implementation, the Conference adopted
      the European Charter on Alcohol, a set of ethical principles and strategies for
      action. Of a number of important issues that frame policy, three deserve mention.
      First, market forces, as opposed to health and social policy decisions are
      increasingly influencing the policy debate. Second, existing policy options to
      reduce alcohol-related harm are unlikely to lead to an increased risk of coronary
      heart disease among older age groups. And third, policy developments and changes
      in drinking patterns in countries of southern Europe are an important driving
      force in European policy on alcohol.

PMID- 9167282
TI  - Alcohol, the individual and society: what history teaches us.
AB  - Drinkers derive both pleasure and pain from drinking, but harm may come also to
      others. Through religious or secular rules, societies have sought to limit these
      "externalities" of drinking. Societal reactions have primarily focused on social
      harms from drinking; policy attention to casualties and chronic health effects is
      fairly recent. Drinking behaviour varies greatly according to the cultural
      framing of alcohol; societal policies tend to vary accordingly. Ecological
      constraints and social norms on preparation and use meant that alcohol was often
      available only sporadically in tribal and village societies. Alcohol production
      has been increasingly industrialized and marketing increasingly globalized in the
      modern era. Now, free trade agreements and the doctrine of consumer sovereignty
      increasingly limit the scope of national alcohol control policies. On the other
      hand, modern society demands exacting standards of attention and care
      incompatible with intoxication, for instance when driving a car or minding
      children. Managing the conflict between these and alcohol's ready availability is
      seen as a wholly individual rather than a societal responsibility. Those who fail
      the task are defined as alcoholics, and modern states have increasingly provided
      treatment for them. While there is a renewed public health concern about the
      externalities of drinking, substantial availability reductions have historically
      often required the mobilization of strong popular movements of remoralization.

PMID- 9167283
TI  - Inequality, deprivation and alcohol use.
AB  - There are major social inequalities in health within societies. Alcohol and
      tobacco are major preventable causes of ill health. Using data from the United
      Kingdom, this paper examines the social distribution of tobacco and alcohol
      consumption; the role that tobacco and alcohol may play in mediating or modifying
      social inequalities in health; and the implications of social distribution for
      policies to reduce harm associated with consumption of alcohol and tobacco. In
      the United Kingdom, as in many other countries, there is clear inverse
      association between socio-economic position and consumption of cigarettes. Over
      the past three decades, the decline in smoking has been more rapid in men and
      women in higher socio-economic groups. United Kingdom suggest that among employed
      men and women, the prevalence of non-drinking shows an inverse association with
      occupational status; heavy drinking differs little; and moderate drinking is more
      common among those of higher socio-economic status. Smoking accounts for perhaps
      25% of the social class difference in coronary heart disease (CHD) mortality,
      more for lung cancer, less for some other diseases. healthier patterns of
      drinking may contribute to the lower CHD rates of higher social classes. Although
      other factors are clearly important in generating social inequalities, it is
      important to take the social distribution of alcohol and tobacco into account
      when formulating policy. For cigarette consumption, there is evidence that in
      lower socio-economic groups demand is more sensitive to price; higher socio
      economic groups are more responsive to health education. There has been less
      research of this nature for alcohol. Available analyses suggest that price
      responsiveness of heavy drinking may be greatest in young men and in those with
      lower incomes. A pricing strategy has important equity implications.

PMID- 9167284
TI  - Why has alcohol consumption declined in countries of southern Europe?
AB  - Alcohol consumption seems to be decreasing in the traditional wine countries of
      southern Europe. This paper describes the evolution of alcohol consumption over
      the last 30 years in France, Greece, Italy, Portugal and Spain. For this purpose,
      data on alcohol production and per capita alcohol consumption in southern Europe
      are examined, and their reliability discussed. To analyse alcohol-related
      mortality, liver cirrhosis death rates are also reviewed. Since 1980 overall
      alcohol production has increased by 10%, while wine production has decreased by
      13%. The consumption of pure alcohol equivalent per capita has continually
      decreased, from a peak of 14 litres per year in 1974 to 10.4 litres in 1992. The
      reduction is dramatic for wine (42.3%) and slight for spirits (4.7%), while beer
      consumption has grown by 36.6%. These data seem to confirm a European trend
      towards the homogenization of drinking patterns. Marketing factors, public health
      policies, the evolution of prices and taxation, European Union agricultural
      policies, a growing awareness of public opinion about the toxicity of alcohol and
      competition from non-alcoholic drinks are all factors that may partially explain
      these observed changes.

PMID- 9167285
TI  - Alcohol and European transformation.
AB  - Against the background of papers and discussions from the East-West seminar at
      the European Conference on Health, Society and Alcohol, the differences and
      similarities in eastern and western European transformation processes are
      discussed. After some remarks on the general nature of eastern transition and
      western integration, the two sides of Europe are compared with respect to various
      alcohol-specific issues. It will be shown that the ongoing transition touches
      alcohol-related phenomena on a broad spectrum, and no single characterization
      (e.g. commercialization and the rise of market interests) is sufficient alone.
      The changing balance between state, markets and civil society provides, however,
      an interesting perspective for comparing alcohol-related changes in various
      European societies. Finally, the prospects for a common European alcohol agenda
      are discussed briefly from the point of view of international mobilization on the
      dimensions of state, markets and civil society. There are signs of increased
      cooperation along all dimensions, but an all-European alcohol agenda seems
      unlikely.

PMID- 9167286
TI  - Alcohol, Europe and the developing countries.
AB  - Although most of the developing countries currently have a lower overall per
      capita consumption of alcohol than the European countries, the rapid rate of
      increase in recent years is highly significant from a public health perspective.
      Excessive alcohol consumption in developing countries leads to substantial
      negative effects on the health and also on the quality of life of the drinking
      individuals and their families. It also causes massive direct and indirect costs
      to these countries that they can ill-afford. Europe has played a major
      facilitatory role for alcohol consumption in the developing countries and its
      continues to have considerable influence directly and indirectly even now.
      Increased international cooperation on scientific as well as policy issues is
      likely to achieve the twin aims of limiting alcohol use and preventing alcohol
      related health and social problems not only in Europe but all over the world,
      including in the developing countries. Important initial steps in this direction
      may be increased exchange of information, developing compatible policies and
      evolving culturally relevant public health measures. In order to achieve any
      success in limiting alcohol related problems, the need to keep a global
      perspective on alcohol is paramount.

PMID- 9167287
TI  - Lost productivity and costs to society.
AB  - Having a single monetary amount that provides an indicator of alcohol misuse can
      be a powerful instrument for those advocating policy action. Existing studies
      suggest that alcohol use in any year may yield costs that are equivalent to 2-5%
      of the gross national product. While useful, such figures do not indicate which
      combinations of policies could yield the greatest net benefits for their
      populations. There may also be interest in the effects of alcohol use on public
      finances or the fairness of both taxes and welfare payments across different
      groups of the population. Which items are identified as being relevant and how
      these effects are measured and valued will depend on which policy question is
      being addressed. There are, however, a number of common issues such as whether
      costing studies should be confined to the heaviest and problematic, how benefits
      of alcohol consumption should be measured, how future benefits in terms of health
      gains should be valued and whether the costs to the drinker are important or only
      those costs which are borne by third parties. There will not always be simple
      answers to these questions. However, even if costing studies are confined to
      third party effects and the most conservative assumptions are taken, it is clear
      that there is powerful evidence that many societies would be better off if action
      is taken to prevent alcohol problems. Research on the effects of alcohol use is
      becoming increasingly sophisticated and this will lead to improvements in costing
      studies. Productivity losses are likely to remain one of the most significant
      costs of alcohol misuse.

PMID- 9167288
TI  - The economics of alcohol.
AB  - The use of economic arguments with regard to four aspects of alcohol policy is
      described and discussed. The first aspect is the impact of a potential reduction
      in alcohol consumption on employment by alcohol production and trade. It is shown
      that employment is quite independent of the level of consumption. The second
      aspect is the opportunity for serving the public health and state finance
      interests at the same time by developing alcohol taxation. The third aspect is
      the relationship between the public revenue from alcohol and the public costs for
      alcohol-related problems. A "polluter pays" principle with regard to alcohol
      would mean higher taxation of alcoholic beverages. The fourth aspect is the need
      for cost-effectiveness analyses to support the choices by the decision makers
      between different alcohol policy options. It is concluded that such analyses
      could have impact on the priorities in public health policy on alcohol.

PMID- 9167289
TI  - Trends in alcohol production, trade and consumption.
AB  - This paper is a survey of the structure and significance of international trade
      in alcoholic beverages in the contemporary world economy. It presents data on the
      level of trade in the main alcoholic beverages for the period since 1970. The
      constant-dollar value of this trade grew by a factor of 2.1 between 1975 and
      1992. It represents approximately one half of the one per cent of the value of
      world trade in all commodities. This proportion has remained very stable over the
      past 20 years. International trade in beer, wine and spirits has greatly extended
      the range of alcoholic beverages available around the world and reduced their
      cost. It has played a large part in the tendency for convergence in the patterns
      of alcohol consumption, as countries diversify away from their dependence on
      locally produced beverages. Traditional spirits-drinking and beer-drinking
      countries have witnessed very rapid increases in the consumption of wine, while
      heavy wine drinking countries have seen rapid growth of the consumption of beer.
      While imported beverages remain relatively unimportant in total consumption of
      alcoholic beverages, they have played a significant role in the growth and
      diversification of alcohol consumption in many countries.

PMID- 9167290
TI  - Regulating unregulated markets.
AB  - Ongoing political and economic changes in the ex-socialist countries have proved
      to be very expensive socially. The sudden transition from a centrally planned to
      a market economy had led to an increase of social problems. One commonly observed
      danger is the rapid increase in alcohol consumption. The rates of total alcohol
      consumption are particularly high in those countries where spirit consumption
      dominates. Considerable pressure is being applied to liberate the alcohol market
      from all restrictions. Inadequate legislation in the new economic situation,
      modifications in value systems, and the general rejection of all legislative
      solutions developed under the previous regime have created a climate conducive to
      the development of an unregulated alcohol market. State administrations have lost
      control of the alcohol market. Previous data on consumption have ceased to be
      reliable sources of information. The dynamic increase in alcohol-related problems
      is dangerous for public health. If this situation is to be corrected, the first
      step must be regulation of the alcohol market.

PMID- 9167291
TI  - Alcohol policy and the public good.
AB  - Despite a diversity of cultural, social and economic experiences with alcohol at
      national level, a broad unity of purpose is emerging within the alcohol problems
      perspective. The scientific basis for that perspective finds its support in a
      sustained international research effort. With the publication in 1994 of the WHO
      report "Alcohol Policy and the Public Good", that perspective has been given
      persuasive empirical underpinning and a sharp focus. Essentially the problems
      perspective suggests that the target for public policy is the prevention or
      alleviation of population-wide alcohol-related problems, with problems broadly
      defined. The test for any policy within this arena is then whether it contributes
      to the achievement of that target. The perspective is thus rational, empirical,
      rooted in the traditions of public health, and readily intelligible to the
      ordinary citizen. Key conclusions emanating from "Alcohol Policy and the Public
      Good" are summarized. That text is rounded off by the challenging assertion that
      "Drinking problems are not carried by an uncontrollable tide. With public will,
      and on the evidence, they are capable of amelioration." A positive response to
      that challenge by the nations of Europe is both necessary and feasible.

PMID- 9167292
TI  - Population level policies on alcohol: are they still appropriate given that
      "alcohol is good for the heart'?
AB  - The research finding that a reduced risk of coronary heart disease is associated
      with alcohol use has been widely disseminated. This paper addresses the
      significance of this research finding for decisions about what kind of alcohol
      harm reduction policies it is appropriate to implement. The public policies of
      greatest concern to the vested interest groups are population-based policies such
      as taxation and restrictions on availability. Other public policies which impact
      on the drinkers' environment are minimum drinking age laws, drink drive
      deterrence, prevention of intoxication in public drinking places and restrictions
      on advertising. A review of the effectiveness of the available strategies
      provided strong support for environmentally focused approaches rather than
      education targeting high-risk drinkers. Many of these environmental strategies
      seem unlikely to have a significant direct effect of reducing "heart healthy'
      drinking by older people. Furthermore, the impact of alcohol on premature
      mortality among the older sectors of the population has to be weighed against any
      possible impact on younger drinkers resulting in loss of or disability in many
      years of life. Given the relative effectiveness of environmental strategies for
      reducing harm and the likely low level of impact of these strategies on the heart
      healthy drinking of older people it is concluded that the evidence of reduced
      risk of coronary heart disease does not preclude their implementation.

PMID- 9167293
TI  - Alcohol and the future health of Europe.
AB  - The impact of alcohol consumption on trends in the European health situation is
      analysed. Particular attention is given to the impact of alcohol on the widening
      of the East-West health gap in Europe. It is concluded that between 1950-75 the
      negative health impact of a rapid increase in per capita alcohol consumption in
      most European countries was hidden behind a strong positive development in many
      other socio-economic determinants of health. Between 1980 and 1995, health trends
      have been more closely parallel to trends in alcohol consumption. Changes in
      alcohol consumption explain a significant proportion of changes in life
      expectancy, particularly in the newly independent states of the former Soviet
      Union. Public health policy on alcohol, as part of a general development of
      public health policies outside the health sector, is important in reducing the
      East-West health gap and sustaining the positive health trend in western Europe.

PMID- 9167294
TI  - What does science have to say?
AB  - This plenary session had particular character. Ten representatives of the
      research world briefly presented what science has to say on different aspects of
      alcohol policy. Major research-based generalizations from a variety of policy
      experiences were brought to the discussion. The panel's composition reflected the
      global map of alcohol studies; the group consisted of four people from English
      speaking countries, four from northern Europe and the Nordic countries and two
      from the Mediterranean part of Europe. The session focused on population
      orientated strategies including political and economic controls on the
      availability of alcohol, advertising and public information campaigns. There was
      discussion of drink driving measures, and of how individual treatment
      interventions relate to the broad field of public health. Contributions from the
      world of nutrition and tobacco control policy were also drawn into the debate.

PMID- 9167295
TI  - The role of non-governmental organizations.
AB  - Non-governmental organizations (NGOs) intervening in the area of alcohol problems
      are varied and have different histories depending on their political, social and
      cultural contexts; some are long-established and often bear a heavy heritage,
      while others have recently arisen from the upheavals in eastern Europe and the
      developing countries. All of them, however, must solve certain ethical problems
      if they are to move away from a hygiene-based approach and focus on individual
      responsibility. The role of NGOs is located between dreaming of a better world
      and rising up against a market-based system where health and the quality of life
      take second place to commercial interests. Furthermore, their role is to be found
      between the impulsive nature of action and the often demotivating process of
      scientific reasoning and analysis. NGOs can intervene flexibly in all the fields
      of information, training, advocacy and assistance. They can readily position
      themselves in the long time-frame required for prevention and in a space freed
      from burdensome administrative procedures. Their actions often appear to entail
      criticism of the authorities; in fact, however, they complement the latter, by
      countering the "hands off" or fatalistic approach of certain communities in the
      face of the alcohol risk.

PMID- 9167296
TI  - Alcohol and health: individual and population perspectives.
AB  - This paper summarizes the relationships between alcohol consumption and health
      from both the individual and the population perspectives. On the individual level
      adverse consequences of alcohol consumption on mortality, morbidity and social
      harm are summarized. The potential health benefits of drinking are listed next,
      especially in the context of trying to balance positive and negative
      consequences. Even though the final decision rests with the individual it is
      suggested that from a health perspective light drinking on a regular basis is
      most advisable. In terms of advice to populations it should be noted that, due to
      the mutual interdependence of drinking behaviour in a society, the average
      individual consumption associated with the lowest individual risk is not
      necessarily the average per capita consumption associated with the lowest
      population risk. Thus, research at the population level has to be integrated with
      individual epidemiological research in order to come up with the best advice for
      the population in any given society.

PMID- 9167297
TI  - Alcohol use and a safe environment.
AB  - Three areas are discussed which illustrate the potential for drinking to increase
      the threat to personal safety, i.e. family harm and disruption, violence and
      crime, and traffic safety. Such threats to safety are especially important in
      that they extend well beyond the individual drinker into the lives of family
      members, friends, work colleagues, and even strangers who can become injured or
      killed in a drinking and driving accident. Thus, alcohol policy is a concern for
      all citizens whose personal safety can be at risk. From this perspective, alcohol
      involved problems are public health and safety issues. Controlled evaluations of
      a number of strategies provide evidence of potential effectiveness to reduce
      problems related to safety.

PMID- 9167298
TI  - Educational approaches.
AB  - Three papers were presented in the session focusing on educational approaches:
      Anu Narusk reported on an Estonian study on the influence of the family on
      adolescents' substance use, Bernadette Roussille presented a French mass media
      campaign aimed at reducing heavy drinking by young people, and Sally Casswell
      analysed the public discourse on alcohol, which is an important part of the
      social and political context in which decisions are taken about public policies.
      Each of the papers highlighted in its own way the complex relationships between
      people's behaviour, its social and cultural context, and the wider economic and
      political environment.

PMID- 9167299
TI  - Place of work, communities and municipalities.
AB  - The Paris conference recognized that although national social policy and
      international research were undoubtedly important, a local dimension to research
      action and planning was essential. The potential for community and municipal
      action was illustrated in a number of papers which are summarized here. It was
      also the subject of a publication in the series associated with the European
      Alcohol Action Plan. The work-place was taken as a significant microcosm of a
      community, where healthy company policy and an enlightened approach to providing
      early help and support to individuals with alcohol-related problems is
      particularly beneficial.

PMID- 9167300
TI  - Where treatment and prevention merge: the need for a broader approach.
AB  - Four papers were presented in a Parallel Session chaired by Dr Forge Gleser
      (Israel) and these are summarized here. The papers were: (1) "Supporting primary
      health care physicians" by Dr Galina A. Korchagina of the Medical Academy of
      Postgraduate Studies, St Petersburg, the Russian Federation; (2) "A new role for
      nurses" by Ms Iveta Kelle, Nursing Consultant, Riga, Latvia; (3) "Broadening the
      base of treatment" by Dr Nina Kerimi of the Research Institute of Preventive and
      Clinical Medicine, Ashgabat, Turkmenistan; and (4) "Primary health care and
      alcohol reduction strategies" by Dr Leo Pas of the Academic Centre of General
      Practice, Free University Brussels, Belgium. Following a discussion, participants
      agreed on the wording of a draft Policy for Primary Health Care and Community
      Action and this is also included here.

PMID- 9167301
TI  - Human prion diseases.

PMID- 9167302
TI  - von Willebrand factor: increased levels are related to poor prognosis in systemic
      sclerosis and not to tissue autoantibodies.
AB  - von Willebrand factor, C-reactive protein, rheumatoid factor, major organ
      involvement, antibodies to extractable nuclear antigen, anti-cardiolipin
      antibodies, anti-centromere antibodies and anti-nuclear antibodies were measured
      in 33 patients with systemic sclerosis. After five years, the nine patients who
      had died had initial levels of von Willebrand factor significantly higher (median
      288 IU/dL, range 150-1170) than levels in the 24 who were still alive (median 148
      IU/dL, range 65-262, Mann Whitney P = 0.0002). Increased levels of von Willebrand
      factor correlated with the time interval from blood sampling until the patient's
      death (Spearman's r = 0.73, P = 0.02). Levels of C-reactive protein, rheumatoid
      factor, and tissue autoantibodies, and age or the number of organs involved were
      unable to predict this outcome. We suggest that endothelial perturbation, as
      indicated by increased levels of von Willebrand factor, is a strong indicator of
      a poor prognosis in systemic sclerosis.

PMID- 9167303
TI  - Monitoring outbreaks of methicillin-resistant Staphylococcus aureus: use of a
      commercial database and personal computer.
AB  - A commercial database and personal computer were used to record relevant
      information on outbreaks of hospital infection associated with methicillin
      resistant Staphylococcus aureus (MRSA). The data were easily stored, amended and
      retrieved, and there was sufficient flexibility and capacity within the data
      fields to allow day-to-day monitoring of the outbreak.

PMID- 9167304
TI  - Detection of methicillin-resistant Staphylococcus aureus: the evaluation of rapid
      agglutination methods.
AB  - The laboratory isolation of methicillin-resistant Staphylococcus aureus (MRSA) is
      now commonplace. Part of the screening procedure to detect MRSA rapidly is a
      reliable particle agglutination test for the presence of S. aureus. Forty
      clinical isolates of MRSA and 12 of coagulase-negative staphylococci were grown
      on the three culture media most likely to be used for the isolation of MRSA.
      Seven particle agglutination kits were evaluated for reliability. Their accuracy
      and speed of agglutination varied, with four kits, Staphaurex Plus, Pastorex
      Staph-plus, Slidex and Staphylase, giving better results with the isolates
      investigated.

PMID- 9167305
TI  - Human erythrocyte antigen expression: its molecular bases.
AB  - This review summarises the considerable body of information now available on the
      molecular bases of human blood group-antigen expression. The elucidation of this
      information has only been possible since the identification, purification, and
      subsequent cDNA cloning of the mRNAs which encode the blood group active
      proteins. The surface components which are responsible for antigen expression are
      divided into two types: carbohydrate and protein. All carbohydrate structures are
      attached covalently to either glycolipids or glycoproteins, and are synthesised
      in the Golgi apparatus of erythropoietic cells (or in other cell lines in
      secreted fluids). As a consequence, the molecular bases of carbohydrate antigens
      lie in polymorphic variation seen in the genes which synthesise these
      carbohydrate structures (i.e. glycosyltransferase enzymes). The structural
      differences in the ABO, Hh and Lewis transferase genes, which alter the substrate
      specificities of these glycosyltransferases and hence generate the different
      antigens, have been defined. The molecular bases underlying the P blood
      glycosyltransferases are unknown. Polymorphism in the remaining 19 blood group
      systems is defined by amino acid sequence changes in erythrocyte membrane
      proteins, which are generated by sequence variation at the DNA level (largely by
      point mutation). Blood group active erythrocyte membrane proteins can be
      categorised broadly into six functional groups: (1) membrane transporters or
      channels: Rh, Diego, Colton, Kidd, KX; (2) Membrane bound enzymes: Kell and
      Cartwright; (3) Structural or assembly proteins: Gerbich and MNSs; (4) Chemokine
      receptors: Duffy; (5) Cell adhesion molecules: Lutheran, LW, Xg, Indian; (6)
      Complement regulatory proteins: Cromer, Knops. The Chido/Rodgers blood group
      system is defined by polymorphic variation in C4 of the complement cascade, and
      is adsorbed passively onto the surface of erythrocytes. This system is not
      considered here. Only two remaining blood group systems defy molecular identity:
      Dombrock and Scianna. The potential clinical applications of such a rapid
      accumulation of data on the molecular bases of blood group antigens is discussed.

PMID- 9167306
TI  - Superoxide, hydrogen peroxide and nitric oxide as signalling molecules: their
      production and role in disease.
AB  - All cells rely on a complex interplay of both extracellular and intracellular
      signals to control their metabolism, growth and differentiation. Recent evidence
      shows that several free radicals and their derivatives are able to act as
      signalling molecules. However, these molecules are inherently reactive towards
      biological materials such as proteins, lipids and DNA. In fact, the destructive
      power of these compounds appears to be harnessed and used by organisms to destroy
      both invading pathogens and tumour cells. Therefore, their use as signals seems
      to be a puzzle. Here, their production, role in signalling, and involvement in
      some diseases are discussed.

PMID- 9167307
TI  - Breast cancer--from clinic to laboratory.
AB  - Breast cancer remains the most common cancer in women in the western world
      despite many years of intensive study. This update reviews some current research
      and its application to the management of patients with breast carcinoma. Specific
      topics include implementation of oestrogen-receptor immunohistochemistry in
      laboratories, the use of established and potential prognostic markers to predict
      clinical outcome and response to treatment, the Breast Screening Programme, and
      the current management of patients at different stages of the disease.

PMID- 9167308
TI  - Escherichia coli O157: occurrence, transmission and laboratory detection.
AB  - The steady increase in the number of reported cases of Escherichia coli O157
      infection is attributable to the proliferation of the organism, and to improved
      clinical and laboratory awareness. E. coli O157 is responsible for sporadic cases
      and outbreaks of diarrhoea, haemorrhagic colitis, haemolytic uraemic syndrome and
      thrombotic thrombocytopenic purpura. The pathogenesis of the organism is not
      fully understood, and the main virulence factors are thought to be the production
      of 'Shiga-like' toxin and adherence to intestinal mucosal cells. The majority of
      outbreaks have taken place in north America, Canada and the United Kingdom. The
      most important source of E. coli O157 infection is under-cooked ground beef and
      other bovine products. The infectious dose is low, person-to-person spread can
      occur, and direct transmission between calves and humans has been demonstrated.
      Infection has been acquired following contact with livestock at farm visitor
      centres. All diarrhoeal stools received in the laboratory should be examined for
      E. coli by culture and toxin detection methods. The presence of 'Shiga-like'
      toxin can be detected by demonstrating cytotoxicity, dot blotting, the polymerase
      chain reaction or by enzyme-linked immunosorbent assay. Serological techniques
      are useful in aiding and supporting a diagnosis. Contamination of meat by E. coli
      O157 probably occurs at slaughter or during processing, therefore, to prevent
      infection it is important to emphasise the dangers associated with the
      consumption of under-cooked beef products.

PMID- 9167309
TI  - The myelodysplastic syndromes.
AB  - The myelodysplastic syndromes (MDSs) are a group of haematological disorders
      found predominantly in the elderly, and are defined by morphological
      abnormalities of the three cell lines. None of the abnormalities is specific for
      MDS but, when combined with active or hyperactive haemopoiesis and refractory
      cytopenia in an elderly person, they suggest the diagnosis. The French-American
      British co-operative group divided MDSs into five types: refractory anaemia;
      refractory anaemia with ring sideroblasts; refractory anaemia with excess of
      blasts; refractory anaemia with excess of blasts in transformation; and chronic
      myelomonocytic leukaemia. The classification was based on the number of blasts in
      the bone marrow, dysplastic features in one or more cell lines, ringed
      sideroblasts, blasts in the peripheral blood, Auer rods in the granulocyte
      precursors and absolute monocytosis. MDS can be a primary condition and of
      unknown aetiology or develop secondary to the action of a known agent such as an
      alkylating agent, chemical or recombinant human granulocyte colony-stimulating
      factor. The pathogenesis of MDS is thought to be a multi-step process which
      begins with a somatic mutation in the pluripotential stem cell, is irreversibly
      altered and acquires a survival advantage. The abnormal clone expands at the
      expense of normal haemopoiesis and undergoes further genetic change to give a
      progressively more malignant phenotype. Present theories of the development of
      MDS are speculative but further research could cast light on the development of
      other haematological disorders.

PMID- 9167310
TI  - Serum siliac acid in patients with multiple myeloma.

PMID- 9167311
TI  - Diagnosing varicella zoster virus infection.

PMID- 9167313
TI  - LISS versus other low ionic suspension solutions for red cells.

PMID- 9167312
TI  - An attempt to demonstrate a serological immune response in patients infected with
      Cyclospora cayetanensis.

PMID- 9167314
TI  - Immunohistochemical staining following melanin bleaching in an atypical
      junctional melanocytic lesion with prominent dermal melanosis.

PMID- 9167315
TI  - Brief psychotherapy in general practice: how do we measure outcome?

PMID- 9167316
TI  - The discipline and literature of general practice.
AB  - In response to a review recently carried out by the Royal College of General
      Practitioners, the British Journal of General Practice is soon to be issued in a
      new and expanded format. While continuing to develop its primary role as a
      leading scientific journal of record, the journal will accommodate a monthly
      selection of integrated news, information and features. The editorial board
      welcomes the opportunities provided by these changes, but wishes to emphasize the
      continuing importance of general practice as a scientific discipline in its own
      right and to reaffirm its commitment to the publication of high-quality, peer
      reviewed original research papers. It is hoped that the newlook journal will have
      a wide appeal. But, as the first-and still the foremost-journal of general
      practice in the world, it will continue to be a journal of record serving both
      its authors and the academic community worldwide.

PMID- 9167317
TI  - Does the BJGP need more fizz and pop?--A Midland Faculty readership survey.
AB  - BACKGROUND: The British Journal of General Practice (BJGP) is the leading primary
      care journal in the world. By impact factor, it ranks 24th of all medical
      journals. However, despite major changes in the journal since its inception in
      1954, there have been no published readership surveys since a limited report in
      1969. AIM: To canvass members of the Midland Faculty and to add to the debate
      about the future of the BJGP. METHOD: A postal questionnaire was sent to a random
      sample of 299 members, fellows and associates of the Midland Faculty asking for
      their views about the BJGP. RESULTS: Two hundred replies were received (a
      response rate of 67%). The median year of qualification of responders was 1981,
      and 32 (16%) held academic posts. Ninety-nine (49%) disagreed with the present
      format of the BJGP, which compared poorly with the British Medical Journal (BMJ)
      in simple rank order of importance. Readership was equal to that of the BMJ (93%
      reading it within 28 days of arrival), but fewer people read it within a week of
      receiving it. The most popular sections were the editorials, original articles
      and letters; least popular were the book reviews and the pull-out magazine,
      Connection. All sections were rated excellent to average. Readers wished for an
      expansion of the BJGP to include clinical reviews, medical politics and humorous
      pieces. Most responders felt that Connection should remain separate. There was
      dissatisfaction with the delay between submission and publication of original
      articles, particularly among the academic general practitioners (GPs). Academics
      and fundholders did not differ from other readers in their views of the content
      or style of the BJGP. Half of the responders stated that the BJGP should be self
      financing and should be open to more advertising. Responders' free comments
      largely related to improving the style of articles and expanding the BJGP.
      CONCLUSION: There is a view that the present BJGP is not relevant to the non
      academic GP. This is probably due to style rather than content. Simple
      comparisons with a weekly multi-disciplinary journal may not be valid. The style
      could be updated to improve retention of information and to highlight areas of
      particular relevance. Readers are satisfied with the core content of the BJGP but
      want it to expand to include humour, clinical reviews and medical politics, for
      example. There is no evidence that the BJGP is more appealing to the academic GP.
      This study supports an expanded BJGP with an improved style.

PMID- 9167318
TI  - Global measures of outcome in a controlled comparison of pharmacological and
      psychological treatment of panic disorder and agoraphobia in primary care.
AB  - BACKGROUND: Panic disorder, with and without agoraphobia, is a prevalent
      condition which presents primarily in general practice. Previous clinical outcome
      studies have been conducted mainly in specialist university departments or
      hospital settings, and have tended to employ complex rating scales that are not
      well suited for use as outcome measures in primary care. AIM: To evaluate the
      outcome, in a primary care setting, of fluvoxamine versus cognitive behaviour
      therapy, each used alone and in combination in a double-blind placebo-controlled
      framework, balanced for therapist contact. METHOD: A total of 149 patients
      satisfying DSMIII-R criteria for panic disorder were randomly allocated to
      receive one of the following: fluvoxamine, placebo, fluvoxamine plus cognitive
      behaviour therapy, placebo plus cognitive behaviour therapy, and cognitive
      behaviour therapy alone. These five treatment groups represent the minimum number
      acceptable for such a comparison to be made. All patients received an identical
      schedule of contact over 13 weeks. Measures of symptom severity, general health
      and social disruption were taken at entry point and end point; measures of change
      in symptoms were taken at end point only. Outcome was reported in terms of brief
      global ratings of severity of illness and change in symptoms, and of ratings of
      general health and social disruption that are suitable for use in general
      practice. RESULTS: All active treatment groups showed statistically significant
      advantages over placebo over a range of outcome ratings. The groups employing
      cognitive behaviour therapy showed the most robust and consistent response.
      CONCLUSION: The brief global measures reported here proved adequate to the task
      of assessing treatment outcome. Results indicate that treatments including
      cognitive behaviour therapy can be effective in the treatment of panic disorder
      and agoraphobia in primary care.

PMID- 9167319
TI  - The facilitator effect: results from a four-year follow-up of children with
      asthma.
AB  - BACKGROUND: A long-term evaluation of the process and outcomes of primary and
      secondary care is required to establish whether audit facilitators can improve
      the care of childhood asthma. AIM: To examine the long-term effect of an
      intervention by an audit facilitator on the management of children with asthma,
      and to investigate the implications for health service costs. METHOD: A 4-year
      follow up was conducted of an intervention and control group totalling 2557
      children aged 1-15 years from 12 general practices in the Tayside region. Primary
      care consultations, prescriptions, hospital contacts and health service costs 1
      year before and 3 years after a facilitator visited practices were recorded. The
      facilitator encouraged the diagnosis and treatment of childhood asthma in the
      intervention group. RESULTS: Favourable changes in consultation patterns,
      prescriptions and reduced hospital admissions seen during the intervention year
      did not persist in subsequent years. Two and three years after the facilitator
      visit the process and outcome of care was similar in both groups. The reduction
      in health service costs seen in the intervention group was equivalent to the cost
      of employing a facilitator. CONCLUSION: The effect of a facilitator lasts only
      for the period of intervention. Enthusiasts will say that improving patient care
      without increasing health service costs justifies the widespread deployment of
      facilitators. Others more interested in long-term outcomes may disagree.

PMID- 9167320
TI  - Adequacy of hormone replacement therapy for osteoporosis prevention assessed by
      serum oestradiol measurement, and the degree of association with menopausal
      symptoms.
AB  - BACKGROUND: Patients on hormone replacement therapy (HRT) for osteoporosis
      prevention rather than menopausal symptom control may be asymptomatic, despite
      inadequate replacement and low serum oestradiol (E2) levels. In the primary
      health care setting, therapeutic monitoring of HRT is not carried out routinely
      so that patients with serum E2 levels inadequate to protect bone may be missed.
      AIM: To determine the proportion of women on transdermal E2 preparations with
      serum E2 levels insufficient to protect bone and to assess the value of a
      questionnaire-derived menopausal symptom score (MSS) for detecting these
      patients. METHOD: A cross-sectional analysis of 45 patients aged 35-70 years
      using transdermal E2 preparations obtained from a computer register of 14500
      patients in a suburban practice. One blood sample was obtained from each patient
      at the time the MSS questionnaire was completed. Serum E2 concentration was
      measured using a fluoroimmunoassay and compared with the MSS. Levels below 150
      pmol/l were considered to be insufficient to protect bone. The diagnostic
      accuracy of the MSS in screening for levels below 150 pmol/l was determined using
      receiver operating characteristic (ROC) curve analysis. RESULTS: The median (95%
      CI) serum E2 was 147 pmol/l (126-198 pmol/l) and levels were below 150 pmol/l in
      24 out of 45 patients. There was no difference in the MSS (median, 95% CI)
      between those with serum E2 < 150 pmol/l (8.5, 5.0-17) and > or = 150 pmol/l
      (9.0, 5.0-14; P = 0.477). The degree of association between the serum E2 and the
      MSS, using the Spearman rank correlation coefficient, rs (95% CI) was small and
      not significant (-0.04, -0.34 to 0.26; P = 0.398). ROC curve analysis revealed an
      area under the curve (95% CI) of 0.51 (0.33-0.68). CONCLUSIONS: More than half
      the women were inadequately replaced to protect against osteoporosis.
      Furthermore, the MSS was of no value in screening for those with low serum E2
      levels. Serum E2 levels should be monitored in women on HRT for osteoporosis
      prevention and the E2 dosage adjusted accordingly.

PMID- 9167321
TI  - Risk factors for late-life insomnia in a representative general practice sample.
AB  - BACKGROUND: Insomnia is widely reported and widely treated in general practice,
      yet relatively little research has focused on the natural history of the
      condition in primary care settings. As a result, there is at present little
      information to enable clinicians to assess insomnia risk, or anticipate outcomes
      in older general practice populations. AIM: To estimate, using 8-year
      longitudinal data, the risk of insomnia onset associated with selected health and
      lifestyle factors. METHOD: Survivors from a nationally representative sample (n =
      1042) of elderly people originally interviewed in 1985 were reassessed in 1989 (n
      = 690) and 1993 (n = 410). At the first follow up in 1989, 84 new cases of
      insomnia were identified (a weighted incidence rate per person per year at a risk
      of 3.1%; 95% CI = 2.7-3.5). In logistic regression analyses controlling for age
      and sex, the risk of insomnia onset was then assessed in relation to the selected
      factors. RESULTS: Three factors assessed in 1985 were significantly and
      independently related to incident insomnia: psychometric ratings consistent with
      depressed mood odds ratio (OR) = 4.41; 95% CI = 3.32-5.43); health index scores
      indicating lower physical health status (OR = 1.19; 95% CI = 1.06-1.31 per unit
      change in scale score); and moderate and low levels of physical activity (OR =
      1.91 and 2.14; 95% CI = 1.91-3.62 and 2.14-3.64 respectively). However, although
      depressed mood represented a major risk factor, the most likely source of risk
      was physical rather than mental ill-health. CONCLUSIONS: Psychiatric, somatic and
      lifestyle factors significantly and independently increase the risk of insomnia
      in older general practice patients. In predicting incident sleep disturbance,
      these factors exceed in importance the age and sex of patients.

PMID- 9167322
TI  - What does a GP consultation cost?
AB  - BACKGROUND: Demand for information regarding the cost-effectiveness of health
      care treatment options is growing. It is necessary to derive unit costs for
      services, such as general practice (GP) consultations, in order to inform the
      economic evaluation. AIM: To review the literature, provide a description of the
      three key steps that should be followed in the costing process and to provide a
      method for updating costs calculated in previous years. METHOD: A literature
      search was carried out to identify references that specifically describe the cost
      of a consultation in general practice. A total of 20 references were extracted,
      categorized and reviewed. A cost-price index for health care goods was obtained
      from the British Medical Association and used to construct a table to allow rapid
      reference and updating of cost results. The costs reported in the literature were
      updated and compared. RESULTS: Twenty published studies referring to the unit
      cost of a GP consultation were located in the searches. Half of these did not
      describe the methodology used to derive the costs; of those that did, less than
      half covered the necessary steps to derive unit costs. The cost of an average 10
      minute consultation in 1995/96 figures was estimated to be 6.90 +/- 2.73 pounds.
      CONCLUSION: Great variation exists regarding the methodology for costing a GP
      consultation. If the methods used are stated explicitly and incorporate the three
      steps described, then results obtained in previous years may be updated using the
      cost-price index as shown (Table 1). Interpretation in this area must be made
      with caution.

PMID- 9167323
TI  - Professional advice on common breastfeeding problems: a primary care study.
AB  - This study investigated the advice given on breastfeeding problems by community
      health professionals involved with breastfeeding mothers in the Huntingdon area.
      A questionnaire on 10 common breastfeeding problems was used, and had a
      significant educational effect on the GP and health visitor groups.

PMID- 9167324
TI  - Like mother, like daughter: a general practice study of maternal influences on
      teenage pregnancy.
AB  - This study confirmed the hypothesis that pregnant teenagers in the 1990s are more
      likely to have a mother who had a teenage pregnancy than non-pregnant teenagers.
      It also found that the daughters of teenage mothers are more likely to continue
      their own pregnancies.

PMID- 9167325
TI  - General practice--a post-modern specialty?
AB  - The 'modern' view of the world is based on the premise that we can discover the
      essential truth of the world using scientific method. The assumption is made that
      knowledge so acquired has been 'uncontaminated' by the mind of the investigator.
      Post-modern theory, however, is concerned with the process of knowing and how our
      minds are part of the process, i.e. our perceptions of reality and the
      relationships between different concepts are important influences on our ways of
      knowing. The values of post-modern theory are those of uncertainty, many
      different voices and experiences of reality and multifaceted descriptions of
      truth. These values are closer to our experience of general practice than the
      'modern' values of scientific rationalism and should be reflected in a new
      curriculum for general practice.

PMID- 9167326
TI  - Scoring system for throat infection.

PMID- 9167327
TI  - The risk of cardiovascular disease in hypertensive patients.

PMID- 9167328
TI  - Skill-mix in primary care.

PMID- 9167329
TI  - Skill-mix in primary care.

PMID- 9167330
TI  - Skill-mix in primary care.

PMID- 9167331
TI  - Overdose and termination of pregnancy.

PMID- 9167332
TI  - Career preferences of medical students: some further answers.

PMID- 9167333
TI  - Methotrexate for psoriasis.
AB  - Methotrexate is an effective antipsoriatic agent and has been widely used to
      treat severe psoriasis since the 1960s. It is especially useful in acute
      generalized pustular psoriasis, psoriatic erythroderma, psoriatic arthritis and
      for extensive chronic plaque psoriasis in patients who are inadequately
      controlled by topical therapy alone. It has not, however, been formally compared
      with other systemic treatments for severe psoriasis such as cyclosporin,
      retinoids or photochemotherapy with psoralen and UVA (PUVA), but in comparison
      with these other therapies it is inexpensive, with correct use, its safety
      profile is favourable. In summary, therefore, it can be used as a short-term
      option to gain control of unstable psoriasis such as pustular psoriasis or
      erythroderma before returning to other modes of treatment, or more often, as long
      term maintenance treatment. The most important potential side-effect is acute
      myelosuppression, which is the cause of most of the rare deaths attributable to
      this therapy for psoriasis. Myelosuppression is more likely in the elderly, in
      patients with renal impairment and/or folate depletion, and with overdose or drug
      interactions. Long-term therapy carries with it a risk of liver fibrosis which is
      related to the dosage regimen employed, and is increased by exposure to other
      hepatic toxins, particularly alcohol. The correlation between the risk of
      development of liver fibrosis, cumulative lifetime dose and duration of treatment
      with methotrexate is not clear-cut, but may have been overstated in some studies.

PMID- 9167334
TI  - Epidermal differentiation characteristics of the psoriatic plaque during short
      contact treatment with dithranol cream.
AB  - Dithranol has been used successfully in the treatment of psoriasis for more than
      75 years, and much in vitro and in vivo research has been done on the elucidation
      of the mode of action of this potent and safe antipsoriatic therapy. In vivo
      research has revealed major effects of dithranol on epidermal proliferation and
      inflammation. Information on the in vivo effects on epidermal differentiation is
      limited. Therefore, the dynamics of a set of differentiation markers (keratin 16,
      filaggrin, keratinocyte transglutaminase, involucrin) and markers for
      proliferation and inflammation (Ki-67, T lymphocytes, polymorphonuclear
      leucocytes) were studied in skin biopsies of six patients with psoriasis during 4
      weeks of dithranol therapy. The treatment regimen involved a short contact
      protocol at our out-patient day treatment centre with an easily washed off cream.
      Treatment resulted in a decrease of the PASI score of 48% in 4 weeks.
      Immunohistochemically, a major decrease of keratin 16 content and virtually
      complete restoration of the filaggrin positive cell layer were seen. These
      changes proved to be significant by comparison of the markers over the group of
      six patients. Although many other topical treatments for psoriasis (occlusive
      therapy and vitamin D3 analogues) result in a prominent reduction in the amount
      of transglutaminase and involucrin positive cell layers, the effect of dithranol
      on these markers is minimal.

PMID- 9167335
TI  - Systemic complement activation in psoriasis vulgaris.
AB  - Nineteen patients with psoriasis vulgaris and no other cause for systemic
      complement activation were studied for evidence of such activation. There was a
      marked elevation in serum C5b-9 complexes with no other significant complement
      abnormalities, and no correlation between C5b-9 levels and disease activity. This
      is the most detailed study of complement in psoriasis yet attempted and confirms
      that complement activation is a feature of psoriasis vulgaris.

PMID- 9167336
TI  - Hidradenitis suppurativa--characteristics and consequences.
AB  - The general characteristics of patients with hidradenitis suppurativa have not
      been previously described in detail. Although rare complications of the disease
      have been described, little is known of the average impact of hidradenitis
      suppurativa. We have now aimed to describe the general characteristics of the
      disease and its impact on patients with an established diagnosis of hidradenitis
      (n = 68) and compare these with those of an unselected general population sample
      (n = 523). Pierced earlobes were more common in patients than in the controls (P
      < 0.02). Female patients were younger (P = 0.0002) and better educated (P <
      0.0001), and fewer had been pregnant (P = 0.0006). The median number of
      treatments prior to referral was two, and an average of 2.7 work days/patient per
      year were lost due to hidradenitis. The self-reported health of patients was
      significantly inferior to that of the general population (P < 0.001), mainly
      because of soreness and restriction of movement. Low-grade hidradenitis
      suppurativa therefore has a considerable impact on the health of patients.
      Previously implied associations with the disease such as the use of cosmetics or
      oral contraceptives, menstrual cycle and body mass index (BMI) were not confirmed
      in our study, although they may influence the course pre-existing disease.

PMID- 9167337
TI  - Consensus meeting on the definition of physical urticarias and urticarial
      vasculitis.

PMID- 9167338
TI  - Malignant blue naevus with distant subcutaneous metastasis.
AB  - Malignant blue naevus is a distinct but rarely documented variant of malignant
      melanoma, and we describe the triple recurrence of a suprapatellar cellular blue
      naevus over 12 years in a middle-aged woman. Staging investigations revealed a
      distant subcutaneous metastasis of the right thigh. Immunohistochemistry of the
      primary lesion and all recurrences showed S-100, HMB-45, NKI/C-3 and Ki-67
      positive cells. However, non-malignant cellular blue naevi from five consecutive
      other patients were all Ki-67 negative. The change from negative to positive Ki
      67 responsivity may therefore be a valuable marker of malignant and metastatic
      potential in early cellular blue naevi.

PMID- 9167339
TI  - Eczema craquele as a pointer of internal malignancy--a case report.
AB  - A case of eczema craquele associated with gastric adenocarcinoma is reported.
      There are localized and generalized forms of eczema craquele, the generalized
      forms differing from the localized types because they can be signs of metabolic
      or internal disease such as cancer. The patterns of the condition are reviewed
      based on the literature and personal observations.

PMID- 9167340
TI  - Pemphigus vulgaris following a hyperimmune response to typhoid booster.
AB  - We report the case of a 46-year-old Indian woman who developed a hyperimmune
      response to a typhoid booster injection in association with the development of
      pemphigus vulgaris. To our knowledge, this association has not previously been
      reported.

PMID- 9167341
TI  - Autoimmune haemolytic anaemia associated with dermatomyositis.
AB  - We report the case of a female patient who at presentation fulfilled the
      diagnostic criteria of dermatomyositis and also had an autoimmune haemolytic
      anaemia. Although autoimmune haemolysis is a well recognized feature of a number
      of autoimmune disorders, it has not previously been described in association with
      dermatomyositis.

PMID- 9167342
TI  - Dermatomyositis and flagellate erythema.
AB  - Flagellate erythema, described by Moulin in 1970 as reminiscent of the lesions
      produced by flogging and by other authors as zebra-like lesions, was noted first
      in association with bleomycin treatment, but later occasionally reported in
      relationship with dermatomyositis, mostly from Japan. It is characterized by
      linear, erythematous, cutaneous streaks, pruriginous or painful, arising on an
      oedematous background and disappearing spontaneously over several weeks. So far,
      fewer than five cases have been reported in association with dermatomyositis, but
      we now present a further one.

PMID- 9167344
TI  - Familial juvenile systemic granulomatosis (Blau's syndrome).
AB  - Blau's syndrome refers to the rare familial presentation of a sarcoid-like
      granulomatous disease classically involving the skin, uveal tract and joints, in
      the absence of pulmonary manifestations. The onset is in childhood, and the mode
      of inheritance is thought to be autosomal dominant. We report a 15-year-old
      female and her 22-month-old daughter who presented with clinical features similar
      to those of Blau's syndrome. In addition to the skin, eye and joint disease, the
      mother also developed neurological involvement. In both patients long-term
      systemic corticosteroids were required to control the disease.

PMID- 9167343
TI  - Oral contraceptives in the treatment of Darier-White disease--a case report and
      review of the literature.
AB  - In this review we illustrated the case of a woman who had perimenstrual
      exacerbations of Darier-White disease. The disease improved markedly with the use
      of continuously administered oral contraceptives. This striking improvement
      without side-effects supports the use of oral contraceptives in women with Darier
      White disease, although its role should be investigated further using controlled
      studies in more patients.

PMID- 9167345
TI  - Depleted cutaneous innervation in familial amyloid.

PMID- 9167346
TI  - Porokeratotic palmoplantar keratoderma discreta--a new entity or a variant of
      porokeratosis plantaris discreta?
AB  - We report a family with hyperkeratotic lesions on palms and soles. The lesions
      became evident in the second to third decade, and there is an autosomal dominant
      mode of transmission. Skin biopsy specimens show a central epidermal depression
      filled by a compact hyperkeratotic plug of columnar parakeratosis, like a broad
      cornoid lamella. The lesions resemble porokeratosis plantaris discreta clinically
      and histologically. The cornoid lamella is a broad, solid keratin plug rather
      than a centrifugally enlarging annular or serpentine ridge as can been seen in
      other types of porokeratosis. Perhaps the lesions of porokeratosis plantaris
      discreta should not be classified as a true porokeratosis but as porokeratotic
      plantar keratoderma discreta. We have therefore called the lesions in our
      patients porokeratotic palmoplantar keratoderma discreta, and suggest that
      porokeratotic palmoplantar keratoderma discreta is a variant of porokeratosis
      plantaris discreta.

PMID- 9167347
TI  - Mossy leg with eccrine syringofibroadenomatous hyperplasia resembling multiple
      eccrine syringofibroadenoma.
AB  - Eccrine syringofibroadenoma (ES) is a histological entity with a polymorphous
      clinical presentation. We describe a patient who had multiple nodules on both of
      his legs resembling lymphoedematous keratoderma (mossy leg or elephantiasis) in
      the absence of any vascular or lymphatic incompetence. The histological features
      were those of ES. A surgical resection was effective. Our case is probably an
      eccrine sweat duct reactive hyperplasia rather than a neoplasia or hamartoma.

PMID- 9167348
TI  - Congenital onychodysplasia of the index fingers--Iso-Kikuchi syndrome. A case
      involving the second toenail.
AB  - We report a case of congenital onychodysplasia of the index fingers (Iso-Kikuchi
      syndrome) in a 2-year-old boy who had nail deformities on both index fingers and
      the left second toe. He had a micronychia of the left index fingernail,
      malalignment and abnormal lunula of the right index fingernail and micronychia
      and malalignment of the left second toenail. Congenital onychodysplasia of the
      index fingers (COIF) is a rare condition characterized by various forms of nail
      dysplasia commonly involving the index fingers, but not infrequently also the
      neighbouring fingers such as the middle fingers and thumbs. The five criteria
      characterizing COIF include the following: (i) congenital occurrence; (ii)
      unilateral or bilateral index finger involvement; (iii) variability in nail
      appearance; (iv)possible hereditary involvement; and (v) frequently associated
      bone abnormalities. The nails of COIF include the full spectrum of nail
      dysplasia, from an irregular lunula, malalignment, micronychia (hypoplastic and
      rudimental), polyonychia (split rudimental), and anonychia, specifically
      affecting the index fingers. Our patient represents various forms of nail
      dysplasia of the both index fingers and left second toe such as micronychia,
      malalignment and abnormal lunula. To our knowledge, the association with second
      toenail dysplasia in COIF has not previously been reported.

PMID- 9167349
TI  - Unilateral naevoid telangiectasia syndrome in pregnancy.
AB  - We report the case of a 22-year-old woman presenting with the unilateral naevoid
      telangiectasia syndrome in her third pregnancy. The development of this is well
      documented but the occurrence in a third pregnancy is unusual. A brief review of
      the literature is included.

PMID- 9167350
TI  - Choice of therapy in porphyria cutanea tarda.

PMID- 9167351
TI  - Acne conglobata: treatment with isotretinoin, colchicine, and cyclosporin as
      compared with surgical intervention.

PMID- 9167352
TI  - Dermatomyositis and malignancy.

PMID- 9167353
TI  - Strict anatomical coexistence of vitiligo and psoriasis vulgaris--a Koebner
      phenomenon?

PMID- 9167354
TI  - Segmental pityriasis lichenoides chronica.

PMID- 9167355
TI  - Episodic vasculitis of the hands and feet in association with Behcet's disease.

PMID- 9167356
TI  - Scar sarcoidosis associated with vitiligo, autoimmune thyroiditis and autoimmune
      chronic hepatitis.

PMID- 9167357
TI  - Pyoderma gangrenosum complicating caesarian section.

PMID- 9167358
TI  - Surgical training in the Defence Medical Services.

PMID- 9167359
TI  - An evaluation of the use of bronchopulmonary lavage in the treatment of plutonium
      oxide inhalation.

PMID- 9167360
TI  - Traumatic diaphragmatic herniation.

PMID- 9167361
TI  - Orthopaedic implant removal at Royal Naval Hospital Stonehouse: the patient's
      perspective.

PMID- 9167362
TI  - Personality, individual differences and command in war: 1982.
AB  - In 1982, a small percentage of Great Britain's armed forces was involved in a
      short but bitter action to recover some territory in the South Atlantic region
      that had been invaded by another nation. As part of a UK Ministry of Defence
      sponsored study, 30 Commanding Officers of British sea, land and air units
      involved in Operation CORPORATE participated between seven and nine years later
      in a research study investigating their individual variations in personality and
      the perceived effects of their experience of Command in War. Ten single-seat,
      fast jet pilots from a slightly younger age group were also investigated.

PMID- 9167363
TI  - Mountains, medicine and mariners.

PMID- 9167364
TI  - From butterflies to babies.

PMID- 9167365
TI  - [Isolation of band-specific (CA)n microsatellites from human chromosome 8q24.1].
AB  - Fourty eight recombinant plasmids containing CA repeats were isolated from human
      chromosome 8q24.1 band-specific pUC19 library. Among them, inserted DNA fragments
      from 12 plasmids were sequenced, and one new highly polymorphic (CA)n
      microsatellite was obtained (coding: D8S7F). It contained 11 alleles. The
      estimated heterozygosity reached 0.84 and 0.83 among Chinese Han Nationality
      people and American Anglo-Saxons respectively. It was assigned to chromosome 8 by
      using a human-rodent hybrid cell panel.

PMID- 9167366
TI  - [On the effect of Chinese lacquer upon the cell division of root tip of Allium
      cepa].
AB  - Chinese Lacquer, as a fine coating, has been studied and applied for thousands
      years. The allergic reaction in Chinese Lacquer on the human skin has also been
      known early. The reaction of Chinese Lacquer on mitosis of cell in plant meristem
      have not been reported yet and was carefully studied in this paper. The result
      showed that Chinese Lacquer induced severe abnormality of mitotic division in
      Allium cepa root tips. This was more obvious in the anaphase and telophase,
      especially in the former phase laggard chromosomes, chromosome bridges, acentric
      fragments and polypolar distribution could be seen frequently. A lot of
      polynuclear bodies were observed in the telophase. Therefore, we think that the
      Chinese Lacquer can be used as a plant cell mutagen, and suggest geneticists and
      physiologists to do more researches on the effects of Chinese Lacquer at the
      genetic variation, metabolism etc.

PMID- 9167367
TI  - [A promoter responsible for over-expression of cholera toxin B subunit in cholera
      toxin A subunit structure gene].
AB  - A promoter sequence, which promotes the transcription of cholera toxin B subunit
      gene, was found in cholera toxin A subunit structure gene. The transcription
      starts at the adenine Located at +833, that is 456bp upstream to the A of the
      initiation codon ATG of cholera toxin B gene. Under the control of the promoter,
      cholera toxin B subunit was over-expressed as high as 200 mg/L at an optimized
      culture condition. The chloramphenicol acetyl transferase gene and beta
      galactosidase could also be efficiently expressed under the direction of the
      promoter. This promoter may be responsible for the 6 fold and 7 fold higher
      expression level of cholera toxin B subunit than cholera toxin A subunit in V.
      cholerae and Escheria coli respectively. The over-expression of CTB may be useful
      in preparing vaccine against cholera and facilitating the construction of peptide
      bearing immunogenic hybrid proteins.

PMID- 9167368
TI  - [Fine physical mapping of yeast chromosome V].
AB  - Electrophoretic karyotype of yeast strain A364a was obtained by pulsed field gel
      electrophoresis and the position of chromosome V on such karyotype was determined
      by means of dot hybridization with chromosome V-specific probe URA3. By cloning
      partially digested BamHI fragments of this chromosome DNA into integrative vector
      Yip5, a gene library specific to this chromosome was constructed. The number of
      the recombinants was much more than theoretically required. After screening probe
      homologous fragments from this library and analysing such fragments with
      restriction enzymes BamHI, EcoRI, HindIII, PstI, and SalI, a fine physical map
      covering about 9.4% of A364a chromosome V (which was estimated as 620kb) was
      constructed. Further colony hybridization with boundary clones will enable us to
      "walk" throughout the whole chromosome.

PMID- 9167369
TI  - Is Helicobacter pylori a gastric carcinogen?

PMID- 9167370
TI  - Experimental model of obstructive jaundice in mongrel dog: study of subsequent
      pathological changes in liver.
AB  - BACKGROUND: Attempts at creating an experimental model of obstructive jaundice in
      large animals have been unsuccessful because of frequent fistulization of the
      ligated bile duct. OBJECTIVES: To produce a model of obstructive jaundice in
      mongrel dogs and to study subsequent serial pathological changes in the liver.
      METHODS: Four techniques were evaluated in four dogs to produce obstructive
      jaundice. After creation of a successful model, subsequent clinical and
      biochemical outcome and serial pathological changes in the liver were studied in
      another 14 dogs. RESULTS: Complete extrahepatic biliary dissection produced a
      model of persistent obstructive jaundice. Serial histological changes included
      inflammation and edema in the first 14 days followed by lymphocytic infiltration
      at 28 days. Fibrosis started by day 7 and resulted in architectural distortion by
      day 21. CONCLUSION: An acute, complete and irreversible model of obstructive
      jaundice can be produced by extrahepatic biliary tree excision and ligation.
      Serial pathological changes showed acute inflammation, followed by fibrosis and
      architectural distortion.

PMID- 9167372
TI  - Pain relief in chronic pancreatitis with epidural buprenorphine injection.
AB  - BACKGROUND: The management of intractable pain in chronic pancreatitis is
      difficult. A novel method for its relief is described. METHODS: Twelve patients
      were given a mixture of buprenorphine (0.3 mg) and blood (10-15 mL) into the
      epidural space. RESULTS: All patients had pain relief lasting up to six months.
      CONCLUSION: Epidural buprenorphine injection is a simple, safe and effective
      method for pain relief in chronic pancreatitis.

PMID- 9167371
TI  - Topical pharyngeal anesthesia without intravenous sedation during upper
      gastrointestinal endoscopy.
AB  - BACKGROUND: There have been conflicting reports about the usefulness of topical
      pharyngeal anesthesia as a pre-endoscopic medication. AIMS: To assess the effect
      of topical pharyngeal anesthesia without intravenous sedatives on easing upper
      gastrointestinal endoscopy. METHODS: 153 consecutive consenting patients were
      randomized to receive either placebo (normal saline) spray (78 patients) or 80 mg
      of 4% lidocaine spray (75 patients). Difficulty of intubation was judged both by
      the patient and the physician on a linear analogue scale. RESULTS: There was no
      significant difference in the scores in the two groups (p > 0.05). The patient
      and physician assessments correlated well. CONCLUSIONS: Topical lignocaine spray
      does not facilitate upper gastrointestinal endoscopy in the absence of
      intravenous sedation.

PMID- 9167373
TI  - Dilatation of radiation-induced esophageal strictures under sublingual
      buprenorphine analgesia: a pilot study.
AB  - BACKGROUND: Pain during dilatation of radiation strictures is a troublesome
      complaint. There is little information on sedation and analgesia during this
      procedure. We performed a pilot study to compare the analgesic efficacy of
      sublingual buprenorphine and intravenous pentazocine during dilatation of
      radiation-induced esophageal strictures. METHODS: Thirty-one patients with
      esophageal cancer who had radiation-induced strictures were randomized to receive
      either buprenorphine 0.2 mg sublingually two hours before dilatation (n = 17) or
      pentazocine 30 mg intravenously five minutes before dilatation (n = 14).
      Dilatation was considered successful if it could be performed to 12 mm diameter
      or more. Pain experienced during dilatation was graded as mild, moderate or
      severe. RESULTS: Sixteen patients in the buprenorphine group and 12 in the
      pentazocine group were dilated to > 12 mm size (p = ns). Twelve and nine patients
      respectively in the two groups experienced mild or no pain; ten and six patients
      had minor side-effects (p = ns). CONCLUSION: Buprenorphine is useful for
      sedoanalgesia during dilatation of radiation-induced strictures of the esophagus.

PMID- 9167374
TI  - Helicobacter pylori and intestinal metaplasia of gastric mucosa.
AB  - BACKGROUND: The role of Helicobacter pylori in stomach carcinogenesis is
      currently under study. H pylori-related chronic gastritis leading to dysplasia or
      intestinal metaplasia (IM) especially of the colonic type is postulated as one of
      the mechanisms. METHODS: We studied 120 patients with or without H pylori
      infection to determine the frequency of occurrence of IM in the stomach. RESULTS:
      IM was found in 16.6% of patients; most cases had the small intestinal type,
      which is not known to have a malignant potential. There was no relation between H
      pylori infection and development of IM. CONCLUSION: H pylori infection leading to
      IM does not appear to be a factor in the genesis of carcinoma stomach in our
      population.

PMID- 9167376
TI  - Tropical pancreatitis.

PMID- 9167375
TI  - Evaluation of plasma serotonin concentration in acute appendicitis.
AB  - BACKGROUND: Due to lack of reliable biochemical/radiological markers, the
      diagnosis of acute appendicitis is based only on clinical features. METHODS: We
      estimated plasma serotonin levels in 48 patients with acute appendicitis
      (histologically proven), 27 patients with abdominal pain of other etiologies, and
      20 healthy controls. RESULTS: The plasma serotonin levels were (mean +/- SD) 36.6
      +/- 12.5 nmol/L, 12.5 +/- 3.6 nmol/L and 10.4 +/- 3.5 nmol/L in the three groups,
      respectively. The levels in patients with acute appendicitis were significantly
      higher (p < 0.001) than in the other groups, giving 93.8% sensitivity and 95.7%
      specificity to the test. CONCLUSION: Plasma serotonin level is a reliable marker
      of acute appendicitis, especially in the first 48 hours.

PMID- 9167377
TI  - Pancreatoduodenectomy in abdominal trauma: a viable alternative.
AB  - Pancreatoduodenectomy was performed in five patients with severe
      pancreatoduodenal trauma following vehicular accidents. Three of them presented
      within five hours of injury and two patients, four and ten days later. Surgery
      was performed within 6-12 hours of hospitalization. All patients underwent
      pancreatoduodenectomy; in one the pancreatic stump was closed completely owing to
      its friability. Three patients survived; two succumbed to ongoing preoperative
      septicemia due to late presentation. The results of pancreato-duodenectomy are
      good when patients are operated on early, before the development of sepsis.

PMID- 9167378
TI  - Synchronous adenocarcinoma and lymphoma of the colon.
AB  - Synchronous lymphoma and adenocarcinoma of the colon are extremely rare. A 32
      year-old woman was referred to us for colon cancer. Investigations revealed two
      primary tumors, one in the cecum and the other in the sigmoid colon. Subtotal
      colectomy with ileorectal anastomosis was performed. Histology revealed the cecal
      tumor to be non-Hodgkin's lymphoma, diffuse small cell type with plasmacytoid
      features. The sigmoid colon tumor was moderately differentiated adenocarcinoma.
      The patient received 6 cycles of chemotherapy postoperatively for lymphoma but
      died of recurrent disease after 17 months.

PMID- 9167379
TI  - Endoscopic stenting of minor papilla for symptomatic pancreas divisum.
AB  - Pancreatitis is one of the presentations of pancreas divisum. Endoscopic
      treatment by dorsal pancreatic duct stenting relieves symptoms in a majority of
      patients. We report a patient with pancreas divisum and calcific chronic
      pancreatitis in whom successful drainage of the dorsal duct with a stent through
      the minor papilla relieved the pain.

PMID- 9167380
TI  - Hydatid cyst in head of pancreas presenting with obstructive jaundice.
AB  - We report a patient with hydatid cyst in the head of the pancreas who presented
      with obstructive jaundice. At operation, the cyst was compressing the common bile
      duct and pancreatic duct. Excision of the cyst with choledochoduodenostomy was
      performed.

PMID- 9167381
TI  - Hepatic artery pseudoaneurysm and hemobilia following laparoscopic
      cholecystectomy.
AB  - Iatrogenic or accidental injury to the right hepatic artery or its branches can
      result in formation of pseudoaneurysm, which may rupture into the biliary system,
      leading to life-threatening hemobilia. We describe one such case following
      laparoscopic cholecystectomy and discuss its management.

PMID- 9167382
TI  - Herpes simplex hepatitis.
AB  - We report a 76-year-old man who presented with hepatitis. IgM antibodies to
      herpes simplex virus were positive and scraping from skin lesions showed presence
      of herpetic inclusion bodies. The patient died 4 days after the onset of illness.

PMID- 9167383
TI  - Volvulus of descending colon with anomalous mesocolon.
AB  - Volvulus of the cecum, transverse colon and sigmoid colon is common. A patient
      with isolated volvulus of the descending colon, leading to gangrene of that
      segment, is reported.

PMID- 9167384
TI  - Pedunculated giant hemangioma of liver.

PMID- 9167385
TI  - Pancreatic tuberculosis mimicking carcinoma.

PMID- 9167386
TI  - Accelerated, low-dose, intradermal hepatitis B vaccine.

PMID- 9167387
TI  - Laparoscopic versus mini-lap cholecystectomy for gallstone disease.

PMID- 9167388
TI  - Immunoproliferative small intestinal disease (IPSID): the Indian scenario.

PMID- 9167389
TI  - Primary esophageal tuberculosis.

PMID- 9167390
TI  - Prophylactic antibiotic project.
AB  - This project evaluated the use of prophylactic antibiotics within two hours prior
      to selected surgical procedures. Even with knee arthroplasty, for which there is
      essentially universal agreement on the need for prophylactic antibiotics, there
      is room for improvement in antibiotic delivery. This is true both in the percent
      of patients receiving antibiotics and the timeliness of administration. Although
      there is some difference of opinion about the advisability of prophylactic
      antibiotics for certain procedures, the preponderance of recent literature
      advocates its use and this is a quality indicator evaluated by JCAHO.

PMID- 9167391
TI  - Cooperative Cardiovascular Project.
AB  - This national project evaluated elements of care for patients admitted for acute
      myocardial infarction. Opportunities for improving processes of care, especially
      in the use and timing of aspirin and thrombolytics, were identified. Additional
      data regarding other quality indicators is available. It is hoped that this data
      can be used to help create or incorporate changes in existing AMI protocols,
      ultimately improving care and outcomes for these patients.

PMID- 9167393
TI  - Transurethral resection of the prostate.

PMID- 9167392
TI  - Pneumonia I and Pneumonia II Projects.
AB  - The need for timely and efficient treatment is assuming even greater
      significance, with pneumonia discharges increasing from 5,862 in 1992 to 7,870 in
      1994. These two projects, involving a total of 13 hospitals, evaluated the
      timeliness of antibiotic administration for pneumonia patients. Baseline data
      revealed opportunities for improving process of care at all hospitals. After
      implementation of improvement plans, the majority of hospitals increased the
      percentage of patients receiving antibiotics within four hours of admission. This
      evaluation of the antibiotic delivery system can also be adapted to other
      diagnoses and medications.

PMID- 9167394
TI  - Outcomes assessment--a surgical perspective.

PMID- 9167395
TI  - Comparative information: another tool in the physician's black bag.

PMID- 9167396
TI  - A change of direction for PROs.

PMID- 9167397
TI  - Reading and writing editorials.

PMID- 9167398
TI  - International affairs. Clinical nurse specialist roles--a professional
      revolution?

PMID- 9167399
TI  - Education. Creating meaningful accreditation practices for the next millennium.

PMID- 9167400
TI  - Inquiry, insights, and history. Help for the history challenged.

PMID- 9167401
TI  - Legal and ethical issues. Professional boundaries in nursing.

PMID- 9167402
TI  - A changing higher education environment.
AB  - Radical changes in contemporary society are forcing colleges and universities to
      alter their time-honored traditions. Economics, demographics, and technology have
      forever changed the university of the past. The public's demand for
      accountability is challenging the relevancy of programs, the value of tenure, and
      the utility of research endeavors. Higher education must focus on serving
      society's needs to survive in the future. New structures, learning environments,
      and technologies must be used. To be successful, colleges and universities must
      be able to respond to opportunities as well as serve as catalysts to create a new
      vision, have a clear sense of the future, and be organized to energize and
      support the efforts to carry out the vision. University faculty and
      administrators must carefully deliberate about higher education--its purpose and
      its methods--and turn those ideas into action to meet society's needs now and
      into the next century.

PMID- 9167403
TI  - Development of leadership within the university and beyond: challenges to faculty
      and their development.
AB  - Environmental changes in health care are driving changes in academic health
      centers. Nursing faculty have an opportunity to shape the changes on campus and
      in future health care delivery systems through participation in campus
      initiatives, but some may lack the skill set to be active participants.
      Leadership is defined as the ability to influence behavior and includes the
      skills of negotiation, facilitation, conflict management, organizational
      improvement, political savvy, systems thinking, personal mastery, and others.
      Opportunities for acquiring stronger leadership skills include feedback,
      partnering, mentoring, formal classes, and 360 degrees feedback.

PMID- 9167404
TI  - Work load issues in clinical nursing education.
AB  - This survey of 22 baccalaureate (BSN) programs was undertaken to describe and
      analyze work load issues in BSN nursing education. Academic careers of nursing
      faculty may be at risk because clinical work load policies generally place less
      value on clinical teaching than on classroom teaching. Research question
      addressed teaching credit hours received for each clinical contact hour,
      remaining weekly hours available for clinical faculty to accomplish service and
      research activities, and student-to-faculty ratios in clinical settings. Seventy
      per cent of the programs surveyed allocated less than 1 teaching credit hour to 1
      clinical contact hour. Nursing faculty who taught clinical courses with 5:1 to
      .25:1 work load credit for face-to-face contact hour ratios needed to work
      between 8 and 24 hours more in face-to-face teaching compared with colleagues
      teaching lecture courses, thus leaving less time for scholarship and service
      activities. Fifty per cent of the programs reported 10 or more students in some
      of the clinical courses. Faculty reported concerns about quality of learning
      experiences and supervisory difficulties as student numbers in clinical courses
      exceeded 8 students/faculty member.

PMID- 9167405
TI  - A proposed framework for teaching and evaluating critical thinking in nursing.
AB  - Critical thinking is now an explicit National League for Nursing outcome
      requirement for nursing education programs, and all nursing faculty currently are
      expected to teach and evaluate critical thinking. However, most of the related
      literature is theoretical and not on the practical level that might be directly
      usable by faculty. This article presents a beginning framework developed by a
      faculty task force at the Indiana University School of Nursing for teaching and
      evaluating critical thinking. The conceptual definition of critical thinking
      underlying the framework reflects the efforts of several hundred experts from
      various disciplines, is maximally inclusive, and lends itself well to
      operationalization in the nursing context. The task force made two assumptions
      for this project: first, that the principles of rational thinking are essentially
      the same at every educational level, although the expertise expected of students
      at different educational levels certainly differs; and, second, that at this time
      a focus on operational as opposed to theoretical definitions for the six
      identified components of critical thinking (interpretation, analysis, evaluation,
      inference, explanation, and self-regulation) would be particularly useful for
      faculty and student understanding.

PMID- 9167406
TI  - Faculty development and curricular change: a process and outcomes model for
      substance abuse education.
AB  - Health care reform carries with it an imperative to change nursing education to
      address emphases on primary care, community-based practice, managed care, and
      cost-containment. comprehensive curricular revision must be accompanied by
      faculty development if those changes are to be supported. This article traces the
      process of faculty development and curriculum change and defines outcomes that
      resulted from a 5-year Faculty Development Project grant to increase nursing
      expertise in alcohol, tobacco, and other drug use and abuse issues. The model has
      broad applicability to faculty development and to curricular revision in general.
      Strategies outlined include independent learning experiences, consultations,
      workshops, seminars, and retreats. A comprehensive evaluation plan that measured
      the impact of the project on faculty, students, institution, and community is
      discussed.

PMID- 9167407
TI  - Hardiness, coping, and burnout in the nursing workplace.
AB  - Relationships among hardiness, coping approach, and burnout were studied in a
      sample of 440 nurses. Within each of the coping approaches used, subjects with
      greater hardiness reported less stress in the form of burnout than did those with
      less hardiness (F = 36.21, df = 1, P = .001). Subjects using direct-active coping
      (changing the stressor, confronting the stressor, finding positive aspects in the
      situation) had the lowest burnout scores, and those using direct-inactive coping
      (ignoring the stressor, avoiding the stressor, leaving the stressor) had the
      highest (t = 2.267, df = 437, P < .012). chi 2 analysis identified independence
      between hardiness and coping approach. Analysis of variance identified no
      interaction between hardiness and coping behavior categories for burnout;
      however, the lowest burnout scores were encountered among nurses with greater
      hardiness who used direct-active coping behaviors. These findings suggest that
      both hardiness and direct-active coping approaches can be used independently or
      in concert to reduce burnout. Rationale is provided for preparing practitioners
      to engage in problem-solving approaches, assertive interaction, and active and
      direct methods of conflict resolution.

PMID- 9167408
TI  - An issue of conflicting rights: nursing student charged with drug trafficking.
AB  - One semester before graduation, a nursing student was charged with a class A
      felony for drug trafficking. The nurse administrator recommended to university
      administration that the student be suspended from all clinical activity until
      charges were resolved. Initially, a summary action was issued by university
      administration to support this recommendation. A summary disciplinary action
      allows for temporary suspension of a student charged with misconduct when the
      student's presence threatens harm to the student or any other person. However,
      after legal review, the summary action was rescinded based on the complexity of
      conflicting interests and rights that required consideration and protection. The
      law provides some guidance but lacks the specificity to move an issue like this
      from equivocal to unequivocal in a short time frame. Consequently, the student
      was allowed to complete the program. Shortly after commencement, the graduate was
      convicted. In retrospect, it was found that ample case law exists allowing for a
      more aggressive defense of a summary action then had been taken. As pointed out
      in Krasnow v. Virginia Polytechnic Institute (1976), standards of student conduct
      established by a university may prohibit action that interferes with the mission
      or functions of the institution, and these standards may go beyond standards
      established by criminal law and may require greater ethical or moral behavior.
      Being prepared for situations such as the one presented here requires that
      schools have in place clearly defined policies and procedures that assure due
      process, allow for disciplinary action, reduce time and energy required to
      resolve conflicts, and assure consistent and fair outcomes.

PMID- 9167409
TI  - Australian nurses' personal constructs about effective nurses--a repertory grid
      approach.
AB  - Repertory grids were completed by nurses (N = 56) enrolled in university courses
      to elicit the personal constructs they used to characterize nurses as effective
      and to elicit the extent to which participants believed themselves to be
      effective nurses. The personal constructs of "good knowledge base," "good
      interpersonal and communication skills," were ranked, respectively, as the four
      most frequently elicited constructs associated with nurses. "Good knowledge
      base," "caring, compassionate," "good clinical skills," and "good decision-making
      and problem-solving skills" were ranked, respectively, as the four most
      frequently elicited constructs associated with "effective" nurses. Cluster
      analysis of individual repertory grids showed that there was a significant
      difference between self-perceptions of participants as effective nurses and the
      nurses they would like to become.

PMID- 9167410
TI  - Indicators of quality in doctoral programs in nursing. American Association of
      Colleges of Nursing.

PMID- 9167411
TI  - Revisiting cancer issues in African Americans.

PMID- 9167412
TI  - Attitudes and practices of African-American physicians toward smoking
      interventions: an earlier study.
AB  - A paucity of data exists regarding the smoking prevention and cessation practices
      of African-American physicians. Advice from a physician is an important strategy
      in helping patients quit smoking. This article presents the results of a national
      survey conducted in the mid- 1980s of African-American physicians about their
      attitudes and practices toward smoking cessation and prevention. In this study,
      an adjusted response rate of 54% was achieved, yielding 188 returned
      questionnaires. Four specific smoking intervention practices were examined as
      dependent variables: (1) exploring patients' feelings about smoking; (2)
      discussing smoking with patients' families; (3) providing educational materials
      to patients; and (4) recording patients' smoking status in the medical charts.
      The proportion of African-American physician smokers in this study (16%) was
      greater than the reported rates (5% to 10%) of other physicians but well below
      the national average for African Americans (32.9%) in 1987. In bivariate analyses
      of the professional and demographic predictors, age, medical specialty, practice
      setting, physician smoking status, and certain attitudinal variables were
      significantly related to smoking intervention practices. Multivariate logistic
      regression analysis showed that older physicians were less likely to discuss
      smoking with a patient's family and to record patient smoking status and that
      respondents who felt their advice was effective were more likely to explore a
      patient's feelings about smoking.

PMID- 9167413
TI  - Comparison of breast screening outcomes from a cancer control intervention for
      African-American and white women in western New York.
AB  - This study's purpose was to compare breast screening outcomes, health practices,
      and risk factors for low-income African-American and white women who participated
      in a multistrategy cancer control intervention. Subjects were recruited from
      their communities to participate in breast screening activities (clinical breast
      examination and mammography testing). Data were collected via a screening intake
      form for a 2-year period (mid- 1994 to mid- 1996). As a result of the
      recruitment. 1444 women enrolled for breast screening services. They included 282
      African Americans. 1079 whites, and 83 other minorities. African-American and
      white women alike reported deficiencies in monthly breast self-examination
      practices and previous mammography use. However, more African-American women than
      white women reported monthly breast self-examination practice (P < 001). More
      white than African-American women reported having had a previous mammogram (P <
      .002). Examination of selected risk factors showed that both African-American
      women and white women had minimum family history. A comparison of breast
      screening outcomes showed that African-American women presented with slightly
      more abnormalities than did white women after undergoing clinical breast exams
      and mammography. However, no significant difference was found when comparing
      these variables. Overall, African-American women were as likely as white women to
      participate in screening activities. There was little difference between these
      groups when comparing screening outcomes, health practices, and risk factors.

PMID- 9167414
TI  - A review of screening and early detection of endometrial cancer and use of risk
      assessment.
AB  - Although the majority of patients with endometrial cancer have a good prognosis,
      subgroups of individuals are at risk of more aggressive disease. Early detection
      programs should target individuals who have the highest risk of advanced disease,
      high-risk histology, and poorly differentiated tumors. This will afford the
      greatest improvement in survival. Screening of the general population is not cost
      effective and indeed may incur iatrogenic morbidity. Recent data also suggest
      that routine screening of patients receiving tamoxifen citrate may not be
      indicated. This area is still being investigated. While screening is not
      appropriate for the general population, a strategy of early evaluation of
      postmenopausal bleeding with judicious use of endometrial biopsy is important for
      the early detection of endometrial cancer. Ultrasound is most effective in
      excluding pathology in symptomatic patients whose biopsy specimen is
      nondiagnostic. Fractional dilation and curettage is reserved for patients with
      abnormal vaginal bleeding who cannot undergo office biopsy or who experience
      persistent symptoms.

PMID- 9167415
TI  - Increased risk in esophageal obstruction with slow-release medications.
AB  - Although medication-induced (pill) esophagitis has been recognized for a long
      time, little data are available on the risk of recently introduced slow-release
      medications. These formulations may have an obstructive capability (undissolved
      medication blocking an obstructed lumen) or may cause tissue irritation
      (continuous leakage from a slowly disintegrating pill). We observed a patient
      with esophageal carcinoma who developed complete obstruction when three Procardia
      XL (nifedipine) extended-release tablets blocked the narrowed lumen. An intact
      Procardia XL tablet and a washed shell as a control were implanted subcutaneously
      in a rat. The intact pill produced a large inflammatory mass: in contrast, no
      inflammatory response was noted at the control site implanted with a washed
      shell. In vitro testing of seven different slow-release medications revealed a
      wide difference in their solubility at a neutral pH and in gastric juice of pH
      1.8 (simulation of esophageal or gastric environment). Theolair-SR (anhydrous
      theophylline, sustained-release) tablets had the highest obstructive, but no
      irritating potential. Cardizem SR (diltiazem hydrochloride) sustained-release
      capsules dissolved promptly without obstructive potential. Adalat CC (nifedipine)
      extended-release tablets also dissolved early at both pH values. Cardizem CD
      (diltiazem hydrochloride) extended-release capsules and Calan SR (verapamil
      hydrochloride) sustained-release oral caplets disintegrated into granules that
      had a low obstructive potential, but their prolonged presence increased the risk
      of tissue irritation. Ecotrin (enteric-coated aspirin) tablets had a high
      obstructive and no irritating potential in the first 24 hours, after which they
      disintegrated and directly contacted the tissue. Procardia XL extended-release
      tablets had an insoluble shell that continued to leak a tissue-irritating content
      even after 48 hours, generating a prolonged obstructive and irritating condition.
      In conclusion, slow-release medications greatly increase the risk of esophageal
      injury. Their obstructive and tissue-irritating potentials differ widely. Slow
      release formulations should be contraindicated in patients who have obstructive
      esophageal and gastric disorders.

PMID- 9167416
TI  - A cerebrospinal fluid turnover in Parkinson's disease.
AB  - In 30 patients with Parkinson's disease (PD) CT scan, isotopic cisternography and
      neuropsychological examination were performed to test possible relationship
      between cerebrospinal fluid (CSF) turnover, intellectual impairment and brain
      atrophy. Pathological cisternography was found in one third of the patients and
      it was positively correlated with the Columbia Rating Scale. Cerebral atrophy on
      CT was found more frequently in patients with earlier onset of PD. Combined
      pathological pattern on CT scan and on cisternography was correlated with
      intellectual decline. We conclude from this study, that in PD intellectual
      deterioration and brain atrophy separately are not connected with abnormal CSF
      turnover.

PMID- 9167417
TI  - An analgesic effect of synthetic human calcitonin in patients with primary
      osteoporosis.
AB  - Examinations were performed in 20 adult male and female patients (pts) suffering
      from acute back pain due to vertebral compression fracture secondary to
      osteoporosis proved by lateral X-rays of the dorso-lumbar spine (Th3-L5), and
      bone mineral density with the method of dual energy X-ray absorptiometry. The
      synthetic human calcitonin (SUC) (0.5 mg) was injected I.M. every day during 28
      days. Analgesic effect was evaluated on 0, 3, 7, 14, 21 and 28th day by patient's
      assessment of functional capacity, and physician's assessment of pain and
      mobility. On the same days biochemical variables of Ca-P homeostasis were
      determined. Treatment with calcitonin resulted in a positive analgesic effect.
      The functional capacity and mobility of pts increased with diminution of pain. No
      significant alterations of Ca-P homeostasis was observed. Mild and transient side
      effects as nausea and tachycardia were negligible. SHC appears to have a
      significant analgesic effect in treatment of primary osteoporosis.

PMID- 9167418
TI  - Cesarean section in grandmultiparas.
AB  - Grandmultiparity which has been considered to be a factor in maternal and
      neonatal morbidity [3], is still high in Libya as compared with European
      countries. A retrospective study of one aspect of this problem concerned the
      Cesarean section in patients who had delivered 6 or more babies. During the
      period of January Ist to the end of December 1993, the records of all
      grandmultiparous women who delivered by a Cesarean section (287 cases) were
      reviewed at Obstetric Department of University Hospital in Benghazi-Libya. The
      incidence was 7.9%. The most common indications for the Cesarean section were:
      fetopelvic disproportion or failure to progress (26.5%), previous Cesarean
      sections (19.5%), malpresentation (16%), placenta praevia and failed induction
      for each of them (7%). The perinatal mortality was 17/1000. We conclude that
      grandmultiparas require Cesarean sections more frequently than
      nongrandmultiparas, especially primary and emergency Cesarean sections. For such
      patients an effective family planning program is necessary.

PMID- 9167419
TI  - Doxazosin-alpha-1-adrenergic antagonists drug in the long-term (3 years).
      Management of benign prostatic hyperplasia.
AB  - To evaluate the efficacy and tolerability of doxazosin in the long-term (3yr.)
      treatment of bladder outflow obstruction resulting from BPH. Data were obtained
      in 64 patients with BPH. The main outcome measures were urodynamic and
      symptomatic evaluation for efficacy. In the three year follow up study on
      doxazosin, including 33 patients remaining on the drug drug and 11 operated
      (total 44) and excluding those who abandoned the therapy or died, the positive
      effect of the treatment was found in 75 percent and failure in 25 percent of
      cases. Doxazosin was well-tolerated and produced both urodynamic and symptomatic
      improvement in men with BPH. Results from clinical trials demonstrate doxazosin
      is effective and safe and well tolerated in both normotensive and hypertensive
      patients with BPH.

PMID- 9167420
TI  - Changes in liver biochemical tests at diagnosis and after propylthiouracil
      therapy for hyperthyroidism.
AB  - We investigated liver biochemical tests at diagnosis and after a 6-week treatment
      with propylthiouracil (PTU) in forty-three patients with hyperthyroidism. At
      diagnosis, 60.5% of the patients had at least one liver biochemical abnormality.
      Elevation of alkaline phosphatase (ALP), alanine (ALT) and aspartate (AST)
      aminotransferase, and gamma-glutamyl transpeptidase (GGT) levels were observed in
      19 (44.2%). 10 (23.3%), 6 (14%) and 6 (14%) of the patients, respectively. After
      6-week treatment with PTU, seven (16.3%) patients developed subclinical
      hepatotoxicity, as evidenced by elevation of ALT levels. Age, sex, type of goiter
      (either diffuse or multinodular) and presence or absence of abnormal liver
      biochemical tests at diagnosis were not significant in determining the
      possibility of the development of hepatotoxicity. These data suggest that liver
      biochemical test abnormalities are frequently observed in hyperthyroid. However,
      presence or absence of these abnormalities do not indicate to the development of
      subclinical hepatoxicity during 6-week PTU therapy.

PMID- 9167421
TI  - Effective palliation for advanced esophageal cancer using intralumenal
      irradiation.
AB  - Palliative treatment by intracavitary irradiation alone has been used in 15
      patients with advanced carcinoma of the esophagus. Most of them had already
      failed other palliative modalities including external irradiation,
      chemoradiotherapy, laserotherapy and dilatation. Intracavitary irradiation was
      carried out with a microSelectron HDR afterloading device and usually 22.5 Gy was
      given in three fractions repeated weekly. Up to three month after treatment,
      complete endoscopic regression was seen in 1 patient, partial endoscopic
      regression in 8 patients, no response in one and progressive disease in 5
      patients. The median survival time is 6.2 months. There were not severe
      complications. We conclude that high dose rate intracavitary irradiation is a
      useful palliative modality in patients with advanced or recurrent esophageal
      cancer.

PMID- 9167422
TI  - Fluid shear stress increases the release of platelet derived growth factor BB
      (PDGF BB) by aortic endothelial cells.
AB  - OBJECTIVES: The aim of this study was to determine the correlation between shear
      stress and the release of Platelet Derived Growth Factor (PDGF BB) by aortic
      endothelial cells. DESIGN AND SETTING: Laboratory in vitro study. MATERIALS:
      Bovine aortic endothelial cells were seeded in fibronectin-coated cylinders at
      1.0 x 10(6) cells/tube and allowed to reach confluence and to adhere for 48
      hours. The experimental groups were subjected to nonpulsatile, laminar flow of
      50, 100, 150 ml/min in polystyrene cylinders (i.d. 10 mm) of a closed circulatory
      loop giving a shear stress on the endothelial cells of 3, 6, 9 dyn/cm2. The
      control group was subjected to similar incubation conditions without flow.
      OUTCOME MEASURES: The release of PDGF BB by endothelial cells was measured by
      ELISA and Western Blot Analysis. RESULTS: Shear stress increased significantly (p
      < 0.01) the release of PDGF BB by endothelial cells. CONCLUSIONS: PDGF BB release
      by endothelial cells may be one of the mechanisms linking hemodynamic forces and
      adaptation of blood vessels wall.

PMID- 9167423
TI  - Heart valve replacement with CarboMedics bileaflet prosthesis: surgical results
      and clinical evaluation. A medium term follow-up.
AB  - From March 1990 to July 1991, 110 patients (44 males, 66 females; mean age 54.44
      +/- 8.8 years) underwent hearth valve replacement with a CarboMedics bileaflet
      prosthesis (CarboMedics Inc, Texas, USA). Preoperative pathophysiologic
      conditions were: aortic stenosis in 32 patients, aortic regurgitation in 22
      patients; mitral stenosis in 27 patients and mitral regurgitation in 14 patients.
      Mitroaortic disease was present in 14 patients but 1 had triple valve disease.
      NYHA class was III or IV in 91 patients (83%). Operative mortality rate was 0.91%
      (1 patients). Actuarial survival rate is 95% at 58 months. Actuarial freedom from
      thromboembolic events in 95% at 58 months. Actuarial freedom from hemorrhage is
      100%. Endocarditis befell in 2 patients; actuarial freedom from this complication
      at 58 months is 95%. Actuarial freedom from reoperation in 99%. We conclude that
      the low incidence of valve related events and the low mortality supports the use
      of the bileaflet valve CarboMedics.

PMID- 9167424
TI  - Combined vascular injuries and limb fractures.
AB  - Blunt arterial injuries secondary to bone fractures are frequently associated
      with nerve, vein and soft tissue lesions. A delayed diagnosis or treatment is the
      main cause of high amputation rate. Thirty-four patients presenting acute
      arterial occlusion (15 cases), false aneurysms (13 cases) or AVFs (6 cases) of
      the extremity were identified between 1983 and 1995. To repair injured arteries,
      ligation (3 cases), patch angioplasty (6 cases), autogenous vein (15 patients) or
      PTFE (4 cases) interposition or bypass grafting were made. Percutaneous
      embolization by coils was performed in 3 AVFs of small limb arteries. Associated
      venous lesions were treated in 9 patients. External fixation of long bone
      fractures was made in 29 patients, before vascular reconstruction, to prevent
      further injury during orthopedic stabilization. Fasciotomies were made in 6
      patients to treat compartmental hypertension. Early reexplorations were necessary
      to correct technical defects in 4 patients. Hyperbaric oxygen therapy was applied
      in 7 patients to control bacterial contamination and improve wound healing.
      Primary (2 cases) or secondary (3 cases) amputations were carried out in
      unsalvageable limbs. Nerve or extensive muscle damage caused poor functional
      outcome in 4 patients. A multidisciplinary diagnostic and management strategy is
      required to improve limb and patient survival.

PMID- 9167425
TI  - ["Odontogenic" anxiety. A study of a population of 1500 students from the public
      schools in the Bari area].
AB  - The authors have carried out a survey regarding 1500 students whose age ranged
      from 9 to 18 years. They belonged to some public schools of Gioia del Colle, a
      small town near the city of Bari. The aim of the study was to evaluate the
      dentist fear, the levels of anxiety and the main reasons or situations which can
      cause it. A questionnaire has been used for this purpose: the Dental Subscale
      Test. Results have shown that the 38.7% of the people questioned, has asserted to
      be afraid of the dentist and that this fear is much more felt in women than in
      men. Moreover has been demonstrated that this fear overcomes amongst those who
      have never undergone a dental treatment and that the degree of anxiety decreases
      from childhood to adulthood. In addition statistics analysis have proved that the
      sensation of choking, the sight and the sound of surgical instruments such as the
      drill and the fear of injections, are amongst those items which can be referred
      as the most frequent sources of anxiety for both males and females.

PMID- 9167426
TI  - Well-being begins with the mouth.

PMID- 9167427
TI  - Managing patient records.

PMID- 9167428
TI  - Knowing how to say goodbye. Dismissing an active patient (2).

PMID- 9167429
TI  - Essix appliances. Provisional anterior prosthesis for pre and post implant
      patients.
AB  - Missing anterior teeth are being replaced by implant-supported restorations quite
      frequently in modern dentistry. Providing the patient with a temporary prosthesis
      prior to or following implant fixture placement must satisfy established esthetic
      and functional criteria. When orthodontic treatment is included as part of the
      overall treatment effort, additional considerations include the retention and
      stabilization of newly established tooth positions. This article describes the
      fabrication, use and advantages of a provisional anterior prosthesis that
      replaces missing teeth prior to or following implant placement.

PMID- 9167430
TI  - Delivery of comprehensive children's dental services using portable dental
      clinics in NYC public schools. A six-year analysis.
AB  - In 1990, the Bureau of Dental Health Services of the New York City Department of
      Health launched a major initiative to modernize a network of school-based dental
      clinics located throughout the city. Since 1913, the bureau has provided dental
      care to public school children; however, the clinics were not properly maintained
      or upgraded, and were in a state of disrepair and obsolescence. Anticipating that
      the survival of the program was in question, the school program was converted to
      a fleet of state-of-the-art portable dental clinics permitting targeting of
      underserved, high-risk poor and immigrant populations. Demographics had changed
      dramatically over the years; the program could now situate services where they
      were needed most, and provide a broader array of care where access was a problem.
      This paper presents a six-year analysis of the program and builds a strong case
      to show that a portable delivery system can equal or in many ways surpass the
      effectiveness and capabilities of a fixed-state approach.

PMID- 9167431
TI  - Processor quality assurance using digital imaging.
AB  - The purpose of this study was to develop and test a computer imaging method for
      assessing longitudinal processor variability. A technique called adaptive
      histogram equalization was used to test deviation in automatic processing when a
      test film is compared with a time-temperature processed standard at two different
      kVp's and film speeds. In a 14-day study we found that the density ranges for the
      standard film did not change, while the density range of the automatically
      processed films changed by a factor of two. These results suggest that if
      automatic processing is to be used for films taken as part of a longitudinal
      study-for example, subtraction-then processor variation can potentially lead to
      incorrect inference of bone gain or loss.

PMID- 9167432
TI  - Nocturnal enuresis.
AB  - The answer to nocturnal enuresis is nocturnal self-awakening. Enuresis alarms
      teach this skill and, therefore, have the highest cure rate and the lowest
      relapse rate of any intervention. An alarm costs the same as a 2-week supply of
      desmopressin. Alarms can be used anytime from age 5 onward if the child elects to
      use one. If an alarm alone is not successful, combining it with medication
      increases the cure rate. The ability to teach a family how to use an enuresis
      alarm is an important part of pediatric office practice.

PMID- 9167433
TI  - Neurodiagnostic techniques.

PMID- 9167434
TI  - Patient Protection Act: the right thing for patients and physicians.

PMID- 9167435
TI  - Wisconsin's long-term health care system scheduled for changes.

PMID- 9167436
TI  - Heat-related illness and death, Wisconsin, 1995.
AB  - This article examines heat-related illnesses and deaths that occurred in
      Wisconsin during the summer of 1995, which was among the warmest seasons on
      record. Death certificates that listed heat exposure as a contributing or
      underlying cause of 154 deaths and ambulance run reports for 454 heat-related
      emergency calls were analyzed. The time and place of these events and patient
      information were used to evaluate risk factors such as age, medical condition,
      physical activity, and environmental temperature. Three-fourths of the deaths and
      nearly half of the heat-related illnesses occurred during or shortly after two
      days of intense heat. Major risk factors for these heat-related illnesses and
      deaths included age, underlying chronic illness, physical exertion, and lack of
      air-conditioning. To reduce the number of illnesses and deaths that occur during
      future heat waves, all residents should be advised to install air-conditioning
      systems in their homes or apartments and encouraged to use them when indoor
      temperatures are uncomfortably warm. Summer weather forecasts should include heat
      index information. During periods of extreme heat, public health advisories
      should be issued encouraging residents to seek shelter in air-conditioned areas
      and to avoid strenuous outdoor activities and prolonged sun exposure. Region
      specific criteria and procedures for issuing public health advisories should be
      developed jointly by the National Weather Service and the US Centers for Disease
      Control and Prevention.

PMID- 9167437
TI  - Epidemic heat stroke in a midwest community: risk factors, neurological
      complications and sequelae.
AB  - We studied the admission rate, risk factors, neurological complications and
      sequelae of heat stroke (HS) during the 1995 heat wave in Madison, Wisconsin. HS
      was epidemic in 1995 (2.3 cases/1000 admissions), compared to the ten-fold lower
      endemic rate in 1994 (0.2/ 1000). There were 11 cases of HS, 9 males and 2
      females. Contributing factors were athletic events (2), working outdoors (3) and
      indoor activity with malfunctioning air-conditioning (6). Medical conditions
      contributing to poor temperature regulation included schizophrenia with
      neuroleptic treatment (2), amyotrophic lateral sclerosis receiving nortriptiline
      (1), multiple sclerosis (1), attention deficit disorder (1), cystic fibrosis (1)
      and alcoholism (1). Acute neurological complications occurred in all patients on
      presentation including coma (8/11.73%), stupor (2/ 11.18%) and seizures
      (1/11.9%). Two patients (1856) had persistent neurological sequelae in the form
      of a pan-cerebellar syndrome while the remaining 9 recovered fully. Importantly,
      avoidable factors contributed to all of the patients with underlying diseases.
      These patients are particularly at risk and should take adequate precautions
      during summer months.

PMID- 9167438
TI  - Sleep, sleep disorders and motor vehicle crashes.
AB  - There is wide consensus that drowsiness and sleep during driving put the driver
      and others at high risk for motor vehicle crashes. A large percentage of both
      private automobile and commercial vehicle crashes and crash fatalities are
      associated with the sleepy driver each year. Sleepiness in persons without sleep
      disorders may occur from potentially preventable causes such as sleep
      deprivation, drinking alcohol or taking sedative medications. Sleepiness also
      occurs uncontrollably in persons with certain sleep disorders. It is important,
      therefore, for persons to have a diagnosis of a sleep disorder, objectively
      confirmed with an MSLT, to be considered for restriction of driving privileges.
      The MSLT serves as a marker for the sleep disorder and also as evidence of
      effective treatment. While sleepiness is widespread, this regulation addresses
      only the highest risk group for attention. Proposed guidelines for sleep related
      disorders and driving in Wisconsin are presented with this background in mind.

PMID- 9167439
TI  - Prostate cancer mortality increases in Wisconsin, 1979-1994.

PMID- 9167440
TI  - What's new in ... medical physics.

PMID- 9167441
TI  - [Studies on Kochiae Fructus. I. Antipruritogenic effect of 70% ethanol extract
      from kochiae fructus and its active component].
AB  - The antipruritogenic effect of the 70% ethanol extract obtained from Kochiae
      Fructus (fruits of Kochia scoparia) and its active components were investigated
      on a compound 48/80-induced pruritogenic model in male ddY strain mice. The
      extract (200, 500 mg/kg, p.o.) inhibited the scratching behavior as a
      pruritogenic indicator. Oleanolic acid oligoglycoside, momordin Ic, isolated from
      the extract also exhibited the inhibition. These results suggest that Kochiae
      Fructus could be used as an antipruritogenic agent and its inhibitory effect may
      be partially attributed to momordin Ic.

PMID- 9167442
TI  - [Effects of photodegradation of nifedipine on dog erythrocyte membranes].
AB  - We studied the effects of nifedipine (NF) on UV-induced photohemolysis of
      erythrocytes in vitro. A suspension in physiologic saline of crythrocytes
      separated from the venous blood sample freshly obtained from a dog was prepared
      and used. NF is a photolabile agent, and this drug was extremely sensitive to the
      long wavelength (365 nm) of UV light. The most abundant photodegradation product
      was a nitroso-derivative which changed into a lactam-derivative in the dog
      erythrocyte suspension with or without irradiation. NF itself showed protective
      effects against photohemolysis of erythrocytes caused by 365 nm of UV light as
      well as hypotonic hemolysis. But NF enhanced the degree of photohemolysis under
      oxygen condition. The photohemolysis enhanced by NF was reduced by thiobarbituric
      acid, indicating an oxidative stress by a radical intermediate of NF to
      photohemolysis. On the other hand, the nitroso-derivative reacted with
      erythrocyte hemoglobin spectroscopically to change into the lactam-derivative. It
      is considered that NF is a phototoxic agent to cause photohemolysis by producing
      a radical intermediate with oxygen and unknown species of hemoglobin degraded
      with the nitroso-derivative of nifedipine photoproduct.

PMID- 9167443
TI  - [Structure of recombinant human serum albumin from Pichia pastoris].
AB  - The structure of recombinant human serum albumin derived from Pichia pastoris
      (rHSA) was analyzed in detail. Complete amino acid analysis was performed by the
      phenyl isothiocyanate precolumn labeling method. The amino terminal sequence was
      determined by the Edman degradation. The carboxyl terminal amino acid was
      determined by digestion with carboxypeptidase, and the carboxyl terminal peptide
      fragment was analyzed by electrospray mass spectrometry. The peptide fragments of
      rHSA digested with Lysylendopeptidase, Endoproteinase Glu-C, or Endoproteinase
      Asp-N were analyzed by electrospray mass spectrometry. The complete amino acid
      composition, the terminal sequences and the complete amino acid sequence of rHSA
      agreed with the primary structure deduced from its cDNA. The elution pattern of
      reduced and carboxymethylated rHSA digested with Lysylendopeptidase and the
      elution pattern of intact rHSA digested with pepsin were respectively similar to
      those of plasma-derived human serum albumin (pHSA). The pattern of CD spectrum of
      rHSA was identical in both shape and magnitude to that of pHSA. 1H-NMR spectra of
      rHSA and pHSA in deuterium oxide showed the same signal patterns in the observed
      region (delta 10.5-0.5 ppm). Cross peaks assigned to the alpha proton-beta proton
      of Asp-1 (delta 4.2/2.8 ppm) and the delta proton-epsilon proton of lysine
      residues (delta 2.8-3.2/1.4-2.0) showed the same cross peak patterns and chemical
      shifts in two-dimensional phase sensitive double-quantum filtered 1H-1H
      correlation spectra of rHSA and pHSA.

PMID- 9167444
TI  - [Hypolipidemic action of F-1394, an acyl-CoA: cholesterol acyltransferase (ACAT)
      inhibitor, in high-fat diet fed beagle dogs].
AB  - In the present study, we investigated the hypolipidemic effect of F-1394, a
      potent and selective inhibitor of acyl-CoA: cholesterol acyltransferase (ACAT),
      in dogs fed with a high-fat diet consisting of regular foods, 5% cholesterol and
      16% fat. The serum cholesterol levels in dogs reached the steady-state 1 week
      after the start of feeding of a high-fat diet and were about 2-fold greater than
      those in normolipidemic dogs. Graded administration of the doses of F-1394 (1-30
      mg/kg/d) to the dogs fed with a high-fat diet prevented the elevation of serum
      cholesterol levels. In the hyperlipidemic dogs fed with a high-fat diet for 14 d
      before the start of the administration of F-1394, the oral administration of F
      1394 at a dose of 1, 3 or 10 mg/kg/d for 21 d reduced the serum cholesterol
      levels in a dose-dependent manner. The estimated ID50 value was 7.2 +/- 0.3
      mg/kg/d p. o. (12.1 +/- 0.5 mol/kg/d p. o.). F-1394 did not affect the body
      weight and no diarrhea was observed by the administration of F-1394. F-1394 at a
      dose of 10 mg/kg/d or more also significantly inhibited the increase of serum
      triglyceride levels 3 h after the feeding of high-fat diet. These results suggest
      that F-1394 inhibits the ACAT activity in the canine small intestine and,
      subsequently, the inhibition of ACAT activity contributes much to the prevention
      of cholesterol absorption via the gut, resulting in a decrease in serum
      cholesterol levels in the dogs fed with high-fat diet. Furthermore, F-1394 may
      also have an inhibitory effect on the triglyceride absorption via the gut, and
      the therapeutical use for postprandial hypertriglyceridemia is expected.

PMID- 9167445
TI  - [Chemiluminescent enzyme immunoassay of cholecystokinin in rat plasma using an
      immuno-affinity column as a pretreatment].
AB  - The cholecystokinin (CCK) plasma concentration of a basal level in a normal rat
      was at a hardly detectable level (a few pg/ml) even using the highly sensitive
      chemiluminescent enzyme immunoassay. In this paper, we prepared an anti-CCK
      F(ab')2 fragment which was made by pepsin digestion from the anti-CCK antiserum.
      The anti-CCK F (ab')2 fragment was immobilized to the Sepharose 4B gel activated
      BrCN and packed to column. We have extracted and concentrated CCK in the rat
      plasma using this column and the CCK assayed by the chemiluminescent enzyme
      immunoassay (CL-EIA) of CCK. The immuno-affinity column extraction system was
      more accurate and precise than a reversed phase gel extraction system. The mean
      recovery of CCK from the rat pooled plasma using the immuno-affinity column was
      62.2% (n = 12) by the proposed CL-EIA. The mean +/- S. E. (n = 3) of the CCK
      concentration in the fasted rat plasma is 3.54 +/- 0.10 pg/ml. The plasma CCK
      concentrations of normal rats and those of camostat administrated rats, could be
      measured by the proposed CL-EIA using the immuno-affinity column as a
      pretreatment.

PMID- 9167446
TI  - Lipoxygenase inhibitors, Part 6. Synthesis of new tetrahydropyrazine and other
      heterocyclic compounds by reaction of hydrazonoyl chlorides.
AB  - Cyclization reactions of alpha-ketoarylhydrazonoyl chlorides with various
      dinucleophiles lead to new 1,4-benzothiazine, quinoxaline, tetrahydropyrazine,
      thiazole, and thiadiazoline derivatives of methyl butanoate or methyl 5
      oxopentanoate. The inhibition of 5-lipoxygenase (LO) was determined by monitoring
      the leukotriene B4 (LTB4) formation of human polymorphonuclear leukocytes (PMNL).
      The IC50 values for the most active compounds with an arylhydrazone structure
      were found to lie between 0.7 and 7.5 microM.

PMID- 9167447
TI  - Synthesis and smooth muscle calcium channel effects of dialkyl 1,4-dihydro-2,6
      dimethyl-4-aryl-3,5-pyridinedicarboxylates containing a nitrone moiety in the 4
      aryl substituent.
AB  - A group of dialkyl 1,4-dihydro-2,6-dimethyl-4-?3-(or 4-)[[(Z)-N- oxo-N-[4
      substituted-phenylmethylene (or vinylmethylene)]-lambda 5- azanyl]phenyl?-3,5
      pyridinedicarboxylates 7a-n were synthesized. Reaction of the C-4 nitrophenyl
      compounds 6a-d with an aryl Grignard reagent afforded the corresponding nitrone
      derivatives 7a-e. Alternatively, reaction of the aryl hydroxylamine compounds 8a
      b prepared by reduction of the nitrophenyl compounds 6c-d with Zn/NH4Cl, or the
      aryl hydroxylamine compounds 8c-d prepared by reduction of the nitrophenyl
      compounds 6e-f with 5% rhodium-on-charcoal and 65% hydrazine hydrate, with a 4
      substituted-benzaldehyde, benzaldehyde or acrolein afforded the respective
      nitrone compounds 7f-n. In vitro calcium channel (CC) antagonist activities were
      determined using the guinea pig ileum longitudinal smooth muscle assay. This
      class of compounds containing a nitrone moiety on the 1,4-dihydropyridine C-4
      phenyl ring exhibited CC antagonist activities (10(-5) to 10(-9) M range)
      relative to the reference drug nifedipine (IC50 = 1.43 x 10(-8) M). Structure
      activity relationships showed that the position of the nitrone moiety on the C-4
      phenyl ring was a determinant of CC antagonist activity where the potency order
      was always meta-nitrone > para-nitrone. The effect of the ester alkyl substituent
      was variable depending upon whether the nitrone substituent was at the meta or
      para-position (meta-nitrone, Et > i-Pr approximately Me; para-nitrone, i-Pr > Me
      approximately Et). In the diethyl ester series of compounds having a meta-nitrone
      moiety, the difference in potency for the various R2-nitrone substituents varied
      by a factor of 15-fold (IC50 = 1.51 x 10(-7) to 9.84 x 10(-9) M range) (4-Cl-C6H4
      > or = 4-Me-C6H4- approximately C6H5- > or = 4-O2N-C6H4- 4-F3C-C6H4- > > CH2 =
      CH-). Whole-cell voltage-clamp studies using isolated guinea pig ventricular
      myocytes indicated that the 4-?3-[(Z)-N-oxo-N-(phenylmethylene)-lambda 5-azanyl]
      phenyl? compound 7c (10 microM) is a calcium channel antagonist which decreased
      the calcium current (ICa).

PMID- 9167448
TI  - Synthesis and in vitro anti-HIV activity of certain 2-(1H-benzimidazol-2
      ylamino)pyrimidin-4(3H)-ones and related derivatives.
AB  - In an ongoing effort to develop novel non-nucleoside human immunodeficiency virus
      inhibitors, a series of substituted 2-(1H-benzimidazol-2-ylamino)pyrimidin-4(3H)
      ones and related derivatives were synthesized via cyclocondensation of 2-ganidino
      1H-benzimidazole with diethyl ethoxymethylenemalonate, substituted diethyl
      malonates, some beta-keto esters and 2-acetylbutyrolactone. From these series of
      compounds, 2-(1H-benzimidazol-2-ylamino)-6-hydroxy-5-phenylpyrimidin -4(3H)-ones
      (5f, NSC 666286) was confirmed to have a moderate in vitro anti-HIV activity.

PMID- 9167449
TI  - Synthesis and cytotoxic action of 3,5-isoxazolidinediones and 2-isoxazolin-5-ones
      in murine and human tumors.
AB  - The 3,5-isoxazolidinediones and 2-isoxazolin-5-ones demonstrated potent
      cytotoxicity against the growth of human Tmolt3 T cell leukemia, murine P388 and
      L1210 leukemias, as well as human HeLa-S3 uterine carcinoma and glioma tumor cell
      growth. The specificity of the 3,5-isoxazolidinedione and 2-isoxazoline-5-one
      derivatives as cytotoxic agents varied with the histological type of tumor cell.
      Selected compounds were active against solid HeLa uterine. KB nasopharynx, skin
      A431, SW-480 adenocarcinoma, osteosarcoma and glioma growth. Selected compounds
      demonstrated in vivo antineoplastic activity against Ehrlich ascites carcinoma
      growth. In L-1210 leukemia cells, the agents blocked DNA and protein synthesis at
      25, 50 and 100 microM over 60 min. The agents were effective in reducing rate
      limiting enzymes in the de novo purine and pyrimidine pathways. In addition they
      suppressed dihydrofolate reductase and ribonucleoside reductase activities with
      moderate inhibition of DNA and RNA polymerase activities. DNA itself was not a
      target of the agents.

PMID- 9167450
TI  - Non-steroidal anti-inflammatory agents, Part 24. Pyrrolidino enaminones as models
      to mimic arachidonic acid.
AB  - The pyrrolidino enaminones, with the carboxylic acid chain fixed at the nitrogen,
      inhibit cyclooxygenase more potently or selectively than 5-lipoxygenase.
      According to the structure-activity relationships discussed the potency depends
      significantly on the chain length of the carboxylic acid, the substitution
      pattern of the heterocyclic moiety and of the phenyl group. Compound 4c is the
      most efficient inhibitor of cyclooxygenase. For the binding profile the unfolded
      conformation of arachidonic acid and the energy-minimized conformations of
      flurbiprofen, diclofenac, ML 3000, and lead compound 4a were compared. In
      addition to known structural features, similar distances of the carboxylic acid
      function and the phenyl residue were found as hypothesized to explain the
      interaction with the active sites of the enzyme. The inhibition of cyclooxygenase
      was determined in a bovine thrombocyte intact cell assay and that of 5
      lipoxygenase using intact bovine PMNLs.

PMID- 9167451
TI  - The baby market.

PMID- 9167452
TI  - Are breast cancers in young women qualitatively distinct?

PMID- 9167453
TI  - Genotypic-resistance assays and antiretroviral therapy.

PMID- 9167454
TI  - Prospects for screening for abdominal aortic aneurysms.

PMID- 9167455
TI  - Streptokinase for empyema.

PMID- 9167456
TI  - Slip-ups in diagnosis of subarachnoid haemorrhage.

PMID- 9167457
TI  - Follow-up study of patients randomly allocated ramipril or placebo for heart
      failure after acute myocardial infarction: AIRE Extension (AIREX) Study. Acute
      Infarction Ramipril Efficacy.
AB  - BACKGROUND: In the Acute Infarction Ramipril Efficacy (AIRE) Study, the effect of
      angiotensin-converting-enzyme (ACE) inhibition on the survival of patients with
      clinical heart failure after acute myocardial infarction (AMI), was assessed. At
      an average follow-up time of 15 months after randomisation, all-cause mortality
      was reduced from 22.6% (placebo group) to 16.9% (ramipril group) representing an
      absolute mortality reduction of 5.7% and a relative risk reduction of 27% (95% CI
      11-40%; p = 0.002). Our aim in this study was to assess the long-term (3 years
      after the AIRE Study closed) magnitude, duration, and reliability of the survival
      benefits observed after treatment with ramipril (target dose 5 mg twice a day)
      when compared with placebo. METHODS: We investigated the mortality status of all
      603 patients recruited from the 30 UK centres involved in the AIRE Study. Through
      government records we were able to confirm the death or survival of all 603
      patients exactly 3 years after the close of the AIRE Study. Follow-up was for a
      minimum of 42 months and a mean of 59 months. The average duration of treatment
      with masked trial medication was 13.4 months for placebo and 12.4 months for
      ramipril. FINDINGS: By 0000 h March 1, 1996, death from all causes had occurred
      in 117 (38.9%) of 301 patients randomly assigned placebo and 83 (27.5%) of 302
      patients randomly assigned ramipril, representing a relative risk reduction of
      36% (95% CI 15-52%; p = 0.002) and an absolute reduction in mortality of 11.4%
      (114 additional 5-year survivors per 1000 patients treated for an average of 12.4
      months). INTERPRETATION: Our data provide robust evidence that administration of
      ramipril to patients with clinically defined heart failure after AMI results in a
      survival benefit that is not only large in magnitude, but also sustained over
      many years.

PMID- 9167458
TI  - Alternative projections of mortality and disability by cause 1990-2020: Global
      Burden of Disease Study.
AB  - BACKGROUND: Plausible projections of future mortality and disability are a useful
      aid in decisions on priorities for health research, capital investment, and
      training. Rates and patterns of ill health are determined by factors such as
      socioeconomic development, educational attainment, technological developments,
      and their dispersion among populations, as well as exposure to hazards such as
      tobacco. As part of the Global Burden of Disease Study (GBD), we developed three
      scenarios of future mortality and disability for different age-sex groups,
      causes, and regions. METHODS: We used the most important disease and injury
      trends since 1950 in nine cause-of-death clusters. Regression equations for
      mortality rates for each cluster by region were developed from gross domestic
      product per person (in international dollars), average number of years of
      education, time (in years, as a surrogate for technological change), and smoking
      intensity, which shows the cumulative effects based on data for 47 countries in
      1950-90. Optimistic, pessimistic, and baseline projections of the independent
      variables were made. We related mortality from detailed causes to mortality from
      a cause cluster to project more detailed causes. Based on projected numbers of
      deaths by cause, years of life lived with disability (YLDs) were projected from
      different relation models of YLDs to years of life lost (YLLs). Population
      projections were prepared from World Bank projections of fertility and the
      projected mortality rates. FINDINGS: Life expectancy at birth for women was
      projected to increase in all three scenarios; in established market economies to
      about 90 years by 2020. Far smaller gains in male life expectancy were projected
      than in females; in formerly socialist economies of Europe, male life expectancy
      may not increase at all. Worldwide mortality from communicable maternal,
      perinatal, and nutritional disorders was expected to decline in the baseline
      scenario from 17.2 million deaths in 1990 to 10.3 million in 2020. We projected
      that non-communicable disease mortality will increase from 28.1 million deaths in
      1990 to 49.7 million in 2020. Deaths from injury may increase from 5.1 million to
      8.4 million. Leading causes of disability-adjusted life years (DALYs) predicted
      by the baseline model were (in descending order): ischaemic heart disease,
      unipolar major depression, road-traffic accidents, cerebrovascular disease,
      chronic obstructive pulmonary disease, lower respiratory infections,
      tuberculosis, war injuries, diarrhoeal diseases, and HIV. Tobacco-attributable
      mortality is projected to increase from 3.0 million deaths in 1990 to 8.4 million
      deaths in 2020. INTERPRETATION: Health trends in the next 25 years will be
      determined mainly by the ageing of the world's population, the decline in age
      specific mortality rates from communicable, maternal, perinatal, and nutritional
      disorders, the spread of HIV, and the increase in tobacco-related mortality and
      disability. Projections, by their nature, are highly uncertain, but we found some
      robust results with implications for health policy.

PMID- 9167459
TI  - Pathology of familial breast cancer: differences between breast cancers in
      carriers of BRCA1 or BRCA2 mutations and sporadic cases. Breast Cancer Linkage
      Consortium.
AB  - BACKGROUND: A few breast cancer cases are attributable to a hereditary
      predisposition to the disease. We aimed to compare the histological features of
      breast cancer in women carrying mutations in the susceptibility genes BRCA1 and
      BRCA2 with controls unselected for family history. METHODS: The morphological
      characteristics of specimens from 440 patients with familial breast cancer,
      including 118 in carriers of BRCA1 mutations and 78 in carriers of BRCA2
      mutations, were compared with those from 547 age-matched controls, unselected for
      family history, by seven pathologists. FINDINGS: Cancers in carriers of BRCA1 (p
      < 0.0001) and BRCA2 mutations (p = 0.04) were, on average, of a higher overall
      grade than in controls. For example, the proportions in grade 3 were 66% of 139,
      41% of 58 and 36% of 368 specimens, respectively. However, when the three grade
      indices were considered independently, breast cancers in BRCA1-mutation carriers
      showed more pleomorphism (p = 0.006), a higher mitotic count (p < 0.0001), and
      less tubule formation than controls (p = 0.006), whereas cancers in BRCA2
      mutation carriers showed less tubule formation (p = 0.003), but no difference in
      pleomorphism or mitotic count. The occurrence of invasive lobular carcinoma and
      invasive ductal carcinoma was not significantly different between carriers of
      BRCA1 or BRCA2 mutations and controls. Medullary or atypical medullary carcinoma
      was, however, found more often in BRCA1 (13%, p < 0.0001) than in BRCA2-mutation
      carriers (3%) or controls (2%). Tubular carcinoma was less common in BRCA2
      mutation carriers. The few mucoid carcinomas were all in familial cases. Carriers
      of BRCA1 mutations showed less ductal carcinoma in situ around the invasive
      lesion than controls (41 vs 56%, p = 0.001). Lobular carcinoma in situ was less
      common in familial cancers (p = 0.013), but differences were not significant for
      BRCA1-mutations or BRCA2-mutation carriers, separately. INTERPRETATION: The
      histology of breast cancers in predisposed women differs from that in sporadic
      cases, and there are differences between breast cancers in carriers of BRCA1 and
      BRCA2 mutations. The findings suggest that breast cancer due to BRCA1, has a
      different natural history to BRCA2 or apparently sporadic disease, which may have
      implications for screening and management.

PMID- 9167460
TI  - Reduction of trachoma in a sub-Saharan village in absence of a disease control
      programme.
AB  - BACKGROUND: Trachoma is a leading cause of blindness in the developing world and
      is most prevalent among people who live in poor rural communities in arid
      locations. METHODS: We analysed the results of surveys of trachoma prevalence in
      Marakissa, a rural village in The Gambia. These surveys were undertaken in 1959,
      by the Medical Research Council, and in 1987 and 1996 by the Gambian National Eye
      Care Programme. FINDINGS: During this 37-year period, the prevalence of active
      inflammatory trachoma among children aged 0-9 years fell from 65.7 cases per 100
      children in 1959 to 2.4 cases per 100 children in 1996. The prevalence also fell
      dramatically among people of 10-19 years (52.5 to 1.4 per 100) and among people
      of 20 years and older (36.7 to 0 cases per 100). INTERPRETATION: The dramatic
      fall in disease occurrence was paralleled by improvements in sanitation, water
      supply, education, and access to health care in the village. Of particular
      importance is that the decline in trachoma occurred without any trachoma-specific
      intervention.

PMID- 9167462
TI  - A boy with heart failure, a thick tongue, and double vision.

PMID- 9167461
TI  - Treatment of multidrug-resistant pulmonary tuberculosis with interferon-gamma via
      aerosol.
AB  - BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is associated with
      substantial morbidity, despite drug therapy. Interferon-gamma, a cytokine
      produced mainly by CD4 T lymphocytes, can activate alveolar macrophages,
      important effector cells in host immunity against Mycobacterium tuberculosis. We
      investigated safety and tolerability of aerosolised interferon-gamma in patients
      with MDR-TB, and assessed its efficacy in terms of sputum-smear grades. METHODS:
      We did an open-label trial of aerosol interferon-gamma given to five patients
      with smears and cultures positive for pulmonary MDR-TB, despite documented
      adherence to therapy. The patients received aerosol interferon-gamma 500
      micrograms three times a week for 1 month. Safety and tolerability were assessed,
      and, as well as routine clinical assessments, sputum samples for smear and
      culture were collected at entry and weekly. Computed tomography scans of the
      chest were done at baseline and after therapy ended. FINDINGS: Interferon-gamma
      was well tolerated by all patients. In all five, bodyweight stabilised or
      increased. Sputum acid-fast-bacillus smears became negative in all patients, and
      the time to positive culture increased (from 17 to 24 days, not significant),
      which suggested that the mycobacterial burden had decreased. The size of cavitary
      lesions was reduced in all patients, 2 months after treatment had ended.
      INTERPRETATION: Preliminary data suggest that aerosol interferon-gamma is a well
      tolerated treatment that may be useful as adjunctive therapy in patients with MDR
      TB who are otherwise not responding well to therapy.

PMID- 9167463
TI  - Second-generation non-nucleosidic reverse transcriptase inhibitor HBY097 and HIV
      1 viral load.

PMID- 9167464
TI  - Blood pressure measurement in severe pre-eclampsia.

PMID- 9167465
TI  - Effect of pregnancy on recovery of lactational bone loss.

PMID- 9167466
TI  - Marker for liver damage in neonates born to mothers with HELLP syndrome.

PMID- 9167467
TI  - Vascular endothelial growth factor in diabetic retinopathy.

PMID- 9167468
TI  - BCG vaccine in insulin-dependent diabetes mellitus. IMDIAB Group.

PMID- 9167469
TI  - Ganglionic local opioid analgesia for refractory trigeminal neuralgia.

PMID- 9167470
TI  - Rifamycin-induced lupus syndrome.

PMID- 9167471
TI  - Penicillin resistance in Bacillus anthracis.

PMID- 9167472
TI  - Autoimmune (idiopathic) thrombocytopenic purpura.

PMID- 9167473
TI  - Country profile. South Africa.

PMID- 9167474
TI  - Auguste D and Alzheimer's disease.

PMID- 9167475
TI  - The crisis in psychiatry.

PMID- 9167476
TI  - The crisis in psychiatry.

PMID- 9167477
TI  - The crisis in psychiatry.

PMID- 9167478
TI  - The crisis in psychiatry.

PMID- 9167479
TI  - Thrombolysis after acute myocardial infarction.

PMID- 9167480
TI  - Prostate cancer.

PMID- 9167481
TI  - Prostate cancer.

PMID- 9167482
TI  - Neutropenia with ticlopidine plus aspirin.

PMID- 9167483
TI  - Escherichia coli O157:H7.

PMID- 9167484
TI  - Tryptophan and depression.

PMID- 9167485
TI  - Reasons for increase in pneumococcal bacteraemia.

PMID- 9167486
TI  - Remission of progressive multifocal leucoencephalopathy after antiretroviral
      therapy.

PMID- 9167487
TI  - Remission of progressive multifocal leucoencephalopathy after antiretroviral
      therapy.

PMID- 9167488
TI  - Breast irradiation in ductal carcinoma-in-situ.

PMID- 9167489
TI  - Are sliding-scale insulin regimens a recipe for diabetic instability?

PMID- 9167490
TI  - p53 in drug resistance in ovarian cancer.

PMID- 9167491
TI  - Corneal epithelial stem-cell transplantation.

PMID- 9167492
TI  - What is the right number of caesarean sections?

PMID- 9167493
TI  - What is the right number of caesarean sections?

PMID- 9167494
TI  - Reduced use of laboratory animals in research institute.

PMID- 9167495
TI  - Rise in organ donations.

PMID- 9167496
TI  - Cost-effectiveness of psychiatric care.

PMID- 9167497
TI  - Images in neuroscience. Clinical genetics, I. Huntington's disease: from disease
      to gene.

PMID- 9167498
TI  - A neurobiological basis of social attachment.
AB  - OBJECTIVE: Although an inability to form normal social attachments characterizes
      many forms of psychopathology, there has been little study of the neural basis of
      social bond formation. The primary purpose of this article is to describe a novel
      approach to the neurobiology of attachment. METHOD: The author reviews animal
      research on two closely related neuropeptides, oxytocin and vasopressin,
      implicated in the central mediation of attachment behaviors. These neuropeptides
      appear to be important for the initiation of pair bonds and parental behaviors as
      well as the infant's response to social separation. RESULTS: Both cellular and
      molecular studies have begun to reveal the mechanisms by which oxytocin and
      vasopressin neural pathways are regulated, leading to a preliminary understanding
      of how these hormones act within the brain to influence complex social behaviors.
      CONCLUSIONS: Although their function in the human brain has yet to be
      demonstrated, the available evidence suggests that oxytocin and vasopressin may
      prove to be important in the pathophysiology of clinical disorders, such as
      autism, characterized by an inability to form normal social attachments.

PMID- 9167499
TI  - Getting the cost right in cost-effectiveness analyses.
AB  - OBJECTIVE: The authors examined different ways of measuring unit costs and how
      methodological assumptions can affect the magnitude of cost estimates and the
      ratio of treatment costs in comparative studies of mental health interventions.
      Four methodological choices may bias cost estimates: study perspective,
      definition of the opportunity cost of resources, cost allocation rules, and
      measurement of service units. METHOD: Unit costs for outpatient services,
      individual therapy, and group therapy were calculated under different assumptions
      for a single community mental health center (CMHC). Using hypothetical service
      utilization profiles, the authors used the unit costs to calculate the costs of
      mental health treatments provided by two programs of the CMHC. RESULTS: The unit
      costs for an hour of outpatient services ranged from $108 to $538. The unit costs
      for an hour of therapy varied by 156%; unit costs were lowest if the management
      perspective was assumed and highest if the economist perspective was assumed. The
      ratio of the outpatient costs in the two treatment programs ranged from 0.6 to
      1.8. CONCLUSIONS: The potential errors introduced by methodological choices can
      bias cost-effectiveness findings based on randomized control trials. These errors
      go undetected because crucial methodological information is not reported.

PMID- 9167500
TI  - Children's thinking in the wake of Challenger.
AB  - OBJECTIVE: The Challenger spacecraft explosion in 1986 offered an opportunity to
      study the thinking of normal children after a sudden and distant disaster,
      differences in thinking among children of different levels of emotional concern
      and different ages, and changes in their thinking over time. METHOD: The authors
      studied six thinking patterns known to characterize childhood posttraumatic
      stress disorder and four additional hypothesized patterns in 153 randomly
      selected children of Concord, N.H. (who watched the explosion on television) and
      Porterville, Calif. (who heard about it later). They compared the structured
      interview responses of the more involved (East Coast) and less involved (West
      Coast) children, of the latency-age children and the adolescents, and of the
      children initially (5-7 weeks after the explosion) and 14 months later. RESULTS:
      The children exhibited the 10 predictable thinking patterns. They initially
      defended themselves, denying the reality of the explosion. They later fantasized
      about it. They tried to cope by seeking additional information on their own, at
      home, and at school. Most children talked about Challenger, but a minority of the
      latency-age youngsters avoided related talk and thoughts. The adolescents
      experienced more paranormal thinking, philosophical changes, and negative
      attitudes. Over the year, omens, paranormal experiences, and Challenger-based
      fantasies tended to disappear, but negative views about institutions and the
      world's future held steady or increased. CONCLUSIONS: The children's thinking
      followed predictable patterns. A higher degree of emotional involvement (East
      Coast children) was strongly linked to these thinking patterns, as was being an
      adolescent. Distant disasters appear to set up commonalities of thought that
      might come to characterize certain generations of children.

PMID- 9167501
TI  - Prevalence and risk factors for posttraumatic stress disorder among chemically
      dependent adolescents.
AB  - OBJECTIVE: This study ascertained the prevalence of posttraumatic stress disorder
      (PTSD) among chemically dependent adolescents and identified factors that
      influence the risk of PTSD after a qualifying trauma. METHOD: The study group
      consisted of 297 adolescents aged 15-19 years who met the DSM-III-R criteria for
      dependence on alcohol or other drugs and who were receiving treatment in seven
      publicly funded Massachusetts facilities. PTSD and other axis I diagnoses were
      assessed by the Diagnostic Interview Schedule. Data on risk factors were
      collected by a specially constructed interview schedule. RESULTS: The lifetime
      prevalence of PTSD was 29.6% (24.3% for males and 45.3% for females), and the
      current prevalence was 19.2% (12.2% for males and 40.0% for females). These
      prevalences reflect a high occurrence of traumatic exposures and a high case rate
      among those who experienced trauma. The risk of PTSD varied with the nature of
      the trauma, the number of traumas experienced, psychiatric comorbidity, and
      familial characteristics. The higher rate of PTSD among females was due to a
      greater frequency of rape, which carries a high risk of PTSD development, and to
      a high rate of comorbid conditions. CONCLUSIONS: The lifetime prevalence of PTSD
      among these chemically dependent adolescents is five times that reported for a
      community sample of adolescents. This extremely high rate provides new
      understanding of the etiologic connection between PTSD and chemical dependence
      and has implications for their treatment.

PMID- 9167502
TI  - Effectiveness and cost of the inpatient treatment of posttraumatic stress
      disorder: comparison of three models of treatment.
AB  - OBJECTIVE: This study compared the outcomes and costs of three models of
      Department of Veterans Affairs (VA) inpatient treatment for posttraumatic stress
      disorder (PTSD): 1) long-stay specialized inpatient PTSD units, 2) short-stay
      specialized evaluation and brief-treatment PTSD units, and 3) nonspecialized
      general psychiatric units. METHOD: Data were drawn from 785 Vietnam veterans
      undergoing treatment at 10 programs across the country. The veterans were
      followed up at 4-month intervals for 1 year after discharge. Successful data
      collection averaged 66.1% across the three follow-up intervals. RESULTS: All
      models demonstrated improvement at the time of discharge, but during follow-up
      symptoms and social functioning rebounded toward admission levels, especially
      among participants who had been treated in long-stay PTSD units. Veterans in the
      short-stay PTSD units and in the general psychiatric units showed significantly
      more improvement during follow-up than veterans in the long-stay PTSD units.
      Greatest satisfaction with their programs was reported by veterans in the short
      stay PTSD units. Finally, the long-stay PTSD units proved to be 82.4% and 53.5%
      more expensive over 1 year than the short-stay PTSD units and general psychiatric
      units, respectively. CONCLUSIONS: The paucity of evidence of sustained
      improvement from costly long-stay specialized inpatient PTSD programs and the
      indication of high satisfaction and sustained improvement in the far less costly
      short-stay specialized evaluation and brief-treatment PTSD programs suggest that
      systematic restructuring of VA inpatient PTSD treatment could result in delivery
      of effective services to larger numbers of veterans.

PMID- 9167503
TI  - Panic disorder and quality of life: variables predictive of functional
      impairment.
AB  - OBJECTIVE: The authors sought to characterize the functional impairment in
      patients with panic disorder, specifically the variance in impairment explained
      by demographic and clinical variables. METHOD: Sixty-two patients with panic
      disorder and 61 comparison subjects from three primary care clinic sites were
      assessed with an adapted form of the Structured Clinical Interview for DSM-III-R.
      Impairment was assessed according to three measures from the 36-item Short-Form
      Health Survey (general health perception, mental health, and physical
      functioning) as well as a principal component factor of the survey. Subjects were
      also compared with respect to personality variables, presence and severity of
      chronic medical illness, and demographic characteristics. Stepwise multiple
      regressions with and without pairwise interactions were used to construct models
      of disability in the patients with panic disorder. RESULTS: The patients with
      panic disorder were more impaired than comparison subjects on each measure of the
      Short-Form Health Survey. The panic disorder diagnosis combined with major
      depression, increasing neuroticism and age, less education, and an interaction
      between panic disorder and age accounted for 48%-77% of the variance in
      impairment scores. Gender and ethnicity contributed modestly to the variance in
      impairment in physical functioning, whereas no contribution was demonstrated for
      chronic medical illness or city of residence. CONCLUSIONS: Factors in addition to
      panic phenomena contribute to the severe impairment seen in patients with panic
      disorder. Further research about factors that affect impairment may help improve
      clinical approaches to this illness.

PMID- 9167504
TI  - Benzodiazepines and exposure-based cognitive behavior therapies for panic
      disorder: conclusions from combined treatment trials.
AB  - OBJECTIVE: Concurrent use of benzodiazepines and psychotherapy for panic disorder
      is a prevalent but highly controversial practice. Although there are many
      rationales for that approach, critics contend that benzodiazepines foster drug
      abuse and dependence and undermine psychosocial treatments in various ways. The
      authors examine that controversy in the light of recent empirical findings and
      offer some tentative conclusions and recommendations. METHOD: Data from studies
      combining benzodiazepines and the leading psychosocial treatment for panic
      disorder, exposure-based cognitive behavior therapy, are reviewed, and their
      application to clinical practice is discussed. RESULTS: The strongest support for
      combined treatment is for the addition of cognitive behavior therapy to
      pharmacotherapy for patients with agoraphobia and for those whose benzodiazepine
      treatment is being discontinued. The greatest problem with combined treatment is
      relapse after drug discontinuance. CONCLUSIONS: Combined treatment may be
      advantageous for some patients, but it must be carefully designed to avoid
      potential problems. Suggestions for that are given.

PMID- 9167506
TI  - Relapse in young paranoid schizophrenic patients: a prospective study of
      stressful life events, P300 measures, and coping.
AB  - OBJECTIVE: The authors investigated the relationship of cognitive and coping
      characteristics to stressful life events at the time of relapse in patients with
      recent-onset paranoid schizophrenia. METHOD: Over 6 years, the authors collected
      data on 41 schizophrenic outpatients aged 18-28 years at recruitment. The
      patients were rated prospectively every 2 weeks with the Brief Psychiatric Rating
      Scale, Scale for the Assessment of Negative Symptoms, Scale for the Assessment of
      Positive Symptoms, Global Assessment of Functioning Scale, and life events
      measures. The Frankfurt Questionnaire of Complaints was used to analyze
      subjective complaints regarding cognitive and coping abilities. The P300 auditory
      event-related potential was measured at recruitment to provide an index of
      information-processing capability. RESULTS: Patients without severe life events
      during the 1 month before relapse had a smaller P300, more subjective complaints,
      and less coping capacity than did relapsed schizophrenic subjects who had severe
      life events in the month before relapse. CONCLUSIONS: Relapses in subjects
      without severe life events were associated with fewer cognitive resources and
      less coping ability. Patients with normal P300 and adequate coping resources
      seemed to be able to deal better with stressful life events.

PMID- 9167505
TI  - Controlled, dose-response study of sertindole and haloperidol in the treatment of
      schizophrenia. Sertindole Study Group.
AB  - OBJECTIVE: This multicenter, double-blind, placebo-controlled study evaluated the
      efficacy and safety of three doses of sertindole (12, 20, and 24 mg/day) and
      haloperidol (4, 8, and 16 mg/day) in the treatment of psychotic symptoms for 497
      hospitalized patients with schizophrenia. METHOD: The patients were randomly
      assigned to one of the medication groups and received treatment for 8 weeks.
      Changes in Positive and Negative Syndrome Scale, Scale for the Assessment of
      Negative Symptoms, Brief Psychiatric Rating Scale, and Clinical Global Impression
      scores were used as evaluations of treatment efficacy. Three rating scales were
      used to assess extrapyramidal symptoms as well as the occurrence of adverse
      events and the use of medications related to extrapyramidal symptoms. RESULTS:
      Both sertindole and haloperidol were comparably effective in the treatment of
      psychosis, and all dose levels were significantly more effective than placebo.
      For the treatment of negative symptoms, only sertindole, 20 mg/day, was
      significantly more effective than placebo. For all extrapyramidal symptom
      measures, sertindole was clinically and statistically indistinguishable from
      placebo, and rates of extrapyramidal symptoms were not dose related. All dose
      levels of haloperidol produced significantly more extrapyramidal symptoms than
      placebo or sertindole. Adverse events associated with sertindole treatment were
      mild in severity. CONCLUSIONS: Sertindole is a new antipsychotic agent effective
      for the treatment of both the positive and negative symptoms of schizophrenia,
      with motor side effects that are indistinguishable from those associated with
      placebo.

PMID- 9167507
TI  - Does risperidone improve verbal working memory in treatment-resistant
      schizophrenia?
AB  - OBJECTIVE: Treatment efficacy in schizophrenia is typically defined in terms of
      symptom reduction. However, new antipsychotic medications could potentially have
      an impact on aspects of disability, such as neurocognitive deficits. The authors
      evaluated the effects of risperidone on verbal working memory, a memory component
      of theoretical interest because of its link to prefrontal activity and of
      practical interest because of its link to psychosocial rehabilitation. METHOD:
      Verbal working memory of 59 treatment-resistant schizophrenic patients was
      assessed as part of a randomized, double-blind comparison of treatment with
      risperidone and haloperidol. Verbal working memory was measured under both
      distracting and nondistracting conditions at baseline and after 4 weeks of both
      fixed- and flexible-dose pharmacotherapy. RESULTS: Risperidone treatment had a
      greater beneficial effect on verbal working memory than haloperidol treatment
      across testing conditions (with and without distraction) and study phases (fixed
      and flexible dose). The treatment effect remained significant after the effects
      of benztropine cotreatment, change in psychotic symptoms, and change in negative
      symptoms were controlled. Neither benztropine status nor symptom changes were
      significantly related to memory performance. CONCLUSIONS: Treatment with
      risperidone appears to exert a more favorable effect on verbal working memory
      than treatment with a conventional neuroleptic. The beneficial effect appears to
      be due, at least partially, to a direct effect of the drug, possibly through
      antagonism of the 5-HT2A receptor. Results from this study suggest that
      pharmacotherapeutic efficacy in schizophrenia treatment could be broadened to
      include impact on neurocognitive abilities.

PMID- 9167508
TI  - Association of ketamine-induced psychosis with focal activation of the prefrontal
      cortex in healthy volunteers.
AB  - OBJECTIVE: Agents that antagonize the N-methyl-D-aspartic acid (NMDA) receptor,
      such as phencyclidine and ketamine, produce an acute psychotic state in normal
      individuals that resembles some symptoms of schizophrenia. The aim of this study
      was to determine which brain regions are involved in NMDA receptor-mediated
      psychosis. METHOD: Positron emission tomography with [18F]fluorodeoxyglucose was
      used to determine cerebral metabolic activity in 17 healthy volunteers while an
      acute psychotic state was induced simultaneously by the administration of
      subanesthetic doses of ketamine. RESULTS: Ketamine produced focal increases in
      metabolic activity in the prefrontal cortex and an acute psychotic state. A
      change in one psychotic symptom, conceptual disorganization, was significantly
      related to prefrontal activation. CONCLUSIONS: These data suggest that the
      prefrontal cortex may be involved in mediating NMDA receptor-induced psychosis.

PMID- 9167509
TI  - Size, shape, and orientation of neurons in the left and right hippocampus:
      investigation of normal asymmetries and alterations in schizophrenia.
AB  - OBJECTIVE: Schizophrenia may involve the two cerebral hemispheres differentially.
      This study was conducted to determine whether left and right hippocampal neuronal
      size, shape, and orientation are normally asymmetrical or asymmetrically affected
      in schizophrenia. METHOD: The authors examined postmortem tissue from the left
      and right hippocampus of 17 normal individuals and 14 individuals with
      schizophrenia. They measured the size, shape, and variability in orientation of
      pyramidal neurons in hippocampal subfields CA1-CA4 and the subiculum in computer
      images of 10-micron coronal sections stained with cresyl violet. RESULTS: Both
      neuronal size and shape showed significant effects of diagnosis and a three-way
      interaction between diagnosis, hemisphere, and subfield. Neurons of the
      schizophrenic subjects were smaller than those of the normal subjects in the left
      CA1, left CA2, and right CA3 subfields; their shape differed from that of the
      normal subjects in the left CA1, left subiculum, and right CA3 subfields. There
      were no group differences in variability of neuronal orientation, but neurons in
      the CA3 genu in the schizophrenic subjects were less variable on the right than
      on the left. In the normal subjects, except for larger neurons in the left than
      in the right CA2 subfield and some left-right differences in variability of
      neuronal orientation, no statistically significant asymmetries were observed.
      CONCLUSIONS: The data confirm that hippocampal neuronal size is decreased in
      schizophrenia and reveal that the shape of neurons is altered, supporting the
      view that hippocampal cytoarchitectural abnormalities may be part of the cerebral
      substrate of schizophrenia. They also provide further evidence that the
      abnormalities are localized and lateralized.

PMID- 9167510
TI  - Similar extent of brain dysmorphology in severely ill women and men with
      schizophrenia.
AB  - OBJECTIVE: The purpose of this study was to determine whether women with chronic,
      severe schizophrenia manifest a widespread deficit in cortical gray matter and
      ventricular enlargement similar to that seen in men with schizophrenia and
      whether this deficit is related to age at onset of illness, length of illness, or
      current illness severity. METHOD: Volumetric measures of head size, cortical gray
      matter, white matter and sulci, and lateral and third ventricles were obtained
      from magnetic resonance images of chronic inpatient schizophrenic women (N = 19)
      and men (N = 18) and healthy comparison women (N = 19) and men (N = 18). Sex and
      group differences were assessed by using a two-factor analysis of variance of
      brain measures. Age was entered as a covariate in assessments of associations
      between brain measures and age at onset and length of illness. RESULTS: The
      schizophrenic patients as a group had less cortical gray matter but comparable
      white matter and significantly more lateral and third ventricular CSF than the
      comparison group. Compared to the combined groups of men, women, regardless of
      diagnosis, had smaller heads, less cortical gray and white matter, and less
      sulcal, lateral, and third ventricular CSF. There were no group-by-sex
      interactions, suggesting that in schizophrenia these aspects of gross volumetric
      morphology in male and female brains are affected equally. There was no
      relationship between cortical gray matter deficit or ventricular enlargements and
      age at symptom onset or length of illness in either men or women with
      schizophrenia, when variance due to age was accounted for statistically.
      CONCLUSIONS: The process that contributes to cortical gray matter deficit in
      schizophrenia appears to affect men and women to a similar extent.

PMID- 9167511
TI  - Stability of diagnosis of obsessive-compulsive disorder in the Epidemiologic
      Catchment Area study.
AB  - OBJECTIVE: This study examined the 1-year temporal stability of a National
      Institute of Mental Health Diagnostic Interview Schedule (DIS) lifetime diagnosis
      of obsessive-compulsive disorder in the Epidemiologic Catchment Area (ECA) study.
      METHOD: In that study, 20,862 individuals, aged 18 years and over, at five sites
      were evaluated by lay interviewers using the DIS (wave 1). All of those who were
      available 12 months later were reinterviewed (wave 2). In the present study, the
      temporal stability of wave 1 obsessive-compulsive disorder diagnoses at wave 2
      was examined, as well as relationships with comorbid diagnoses. The consistency
      of reports of "new-onset" illness was also examined. Factors contributing to
      these measures were evaluated. RESULTS: The temporal stability of the diagnosis
      of obsessive-compulsive disorder was very low. Subjects with a stable diagnosis
      of obsessive-compulsive disorder had a higher rate of both obsessions and
      compulsions, an earlier age at onset, and more comorbid anxiety, affective, and
      alcohol abuse/dependence disorders at initial assessment. The originally reported
      1-year incidence estimates for obsessive-compulsive disorder primarily reflect
      data from subjects at wave 2 who reported the onset of symptoms as preceding the
      wave 1 interview. Older and less-educated subjects had significantly higher error
      rates in reporting onset. CONCLUSIONS: The DIS diagnosis of obsessive-compulsive
      disorder has poor validity, leaving the true incidence and prevalence of the
      disorder unknown. Older and less-educated subjects require special attention in
      the design of instruments for use with community samples.

PMID- 9167512
TI  - Two-year follow-up of inpatients with dissociative identity disorder.
AB  - OBJECTIVE: A group of 135 inpatients with dissociative identity disorder was
      followed for 2 years to monitor treatment outcome. METHOD: Fifty-four of the
      patients were located and reassessed after a 2-year period through the use of the
      same self-report measures and structured clinical interviews that had been
      initially administered. RESULTS: The patients showed marked improvement on
      Schneiderian first-rank symptoms, mood and anxiety disorders, dissociative
      symptoms, and somatization, with a significant decrease in the number of
      psychiatric medications prescribed. Patients who were treated to integration were
      significantly more improved than those who had not yet reached integration.
      CONCLUSIONS: These findings, although preliminary, provide empirical validation
      of previous clinical impressions that patients with dissociative identity
      disorder may respond well to treatment.

PMID- 9167513
TI  - Specific major mental disorders and criminality: a 26-year prospective study of
      the 1966 northern Finland birth cohort.
AB  - OBJECTIVE: The purpose of the study was to examine the quantitative risk of
      criminal behavior associated with specific mental disorders. METHOD: An
      unselected 1966 birth cohort (N = 12,058) in Northern Finland was prospectively
      studied until the end of 1992. The investigation started during the mothers'
      pregnancy, and the data on the subjects' family characteristics, mental and
      physical development, living habits, psychiatric morbidity, and criminal records
      were gathered at various times. RESULTS: The prevalence of offenses was the
      highest among males with alcohol-induced psychoses and male schizophrenic
      subjects with coexisting alcohol abuse, and more than half of the schizophrenic
      offenders also had problems with alcohol. Eleven (7%) of the 165 subjects who
      committed violent crimes were diagnosed as psychotic. Male schizophrenic subjects
      had a moderately high risk for violent offenses, but the risk for other types of
      crimes was not elevated significantly. Odds ratios for criminal behavior were
      adjusted according to the socioeconomic status of the childhood family and were
      the same as or slightly lower than the crude odds ratios for all disorders except
      schizophrenia and mood disorders with psychotic features. CONCLUSIONS: The
      results indicate that the risk of criminal behavior was significantly higher
      among subjects with psychotic disorders, even though the socioeconomic status of
      the childhood family was controlled. The higher risk for violent behavior was
      associated especially with alcohol-induced psychoses and with schizophrenia with
      coexisting substances abuse. The results suggest that schizophrenia without
      substance abuse may also be associated with a higher risk of offenses, but this
      finding is tentative and requires further investigation.

PMID- 9167514
TI  - Persistent delirium following cessation of heavy alcohol consumption: diagnostic
      and treatment implications.

PMID- 9167515
TI  - Psychophysiological protective factors for male subjects at high risk for
      criminal behavior.
AB  - OBJECTIVE: This study examines the role of elevated autonomic nervous system
      reactivity in protecting individuals at high risk for criminal behavior from
      antisocial outcomes. The authors hypothesized that subjects with criminal fathers
      who did not become criminals themselves were biologically protected from such an
      outcome because of, in part, heightened responsiveness of the autonomic nervous
      system. METHOD: Ninety-four male subjects were placed into one of four study
      groups: criminal with criminal father (N = 26), noncriminal with criminal father
      (N = 24), criminal with noncriminal father (N = 20), and noncriminal with
      noncriminal father (N = 24). Skin conductance and heart rate data were gathered
      in an orienting paradigm. RESULTS: Skin conductance and heart rate orienting
      reactivity were found to be significantly higher in the group of noncriminal
      subjects with criminal fathers than in the other three groups. CONCLUSIONS: For
      subjects at high risk for criminal behavior, heightened autonomic nervous system
      responsiveness appears to be associated with lower likelihood of criminal
      outcome.

PMID- 9167516
TI  - Stress reactivity in bipolar patients and its relation to prior history of
      disorder.
AB  - OBJECTIVE: Two questions were posed: Does stress precipitate episodes of bipolar
      I disorder, and does sensitivity to stress differ in episodes later in the course
      of illness compared to early ones? METHOD: Fifty-two patients with bipolar I
      disorder were followed longitudinally for up to 2 years; clinical course was
      monitored, and interview assessments of life events were made every 3 months.
      RESULTS: The patients who had episodes of illness during follow-up had
      experienced significantly more severe stressors and more total stress in the
      preceding 6 months, and more total stress in the preceding 3 months, than those
      without episodes. Inconsistent with Post's stress "sensitization" hypothesis,
      patients with more prior episodes were more likely to have episodes following
      major stressors, and they relapsed more rapidly. CONCLUSIONS: Stressors may
      precipitate episodes of bipolar illness, especially for patients with more prior
      episodes. Different versions of the stress sensitization model remain to be
      tested.

PMID- 9167517
TI  - Unnatural practices, unspeakable actions: a study of delayed auditory feedback in
      schizophrenia.
AB  - OBJECTIVE: It has been suggested that auditory hallucinations and delusions of
      control in persons with schizophrenia could involve a disconnection between an
      "intention center" and a "monitoring center." METHOD: To test this model
      directly, the authors used a delayed auditory feedback paradigm in which the
      subject hears his or her own speech delayed electronically by a fraction of a
      second. In normal, subjects this produces dysfluency, which is thought to occur
      because an expectancy about the perceptual arrival of speech, formed in a
      monitoring center on the basis of corollary discharge from an intention center,
      is violated. If, however, a disconnection were present in schizophrenia, such an
      expectancy would not be formed; hence, less dysfluency should occur. Fifteen
      patients with chronic schizophrenia (10 of whom experienced auditory
      hallucinations and/or delusions of control) and 19 normal subjects were studied.
      RESULTS: Rather than exhibiting less dysfluency than the normal subjects,
      patients with delusions and/or hallucinations exhibited significantly more
      dysfluency. CONCLUSIONS: These results do not support a cognitive model of
      disconnection.

PMID- 9167518
TI  - Meta-analysis of postmortem studies of Alzheimer's disease-like neuropathology in
      schizophrenia.
AB  - OBJECTIVE: To evaluate the hypothesis that patients with schizophrenia who have
      been treated with neuroleptics have a high rate of Alzheimer's disease-like
      neuropathology. METHOD: Neuropathological studies indicating the presence or
      absence of Alzheimer's disease-like neuropathology in the postmortem brains of
      patients with schizophrenia, normal comparison subjects, and comparison subjects
      who had affective disorder were evaluated with Mantel-Haenszel chi-square and
      odds ratio analyses. RESULTS: Ten studies with relevant data were reviewed; none
      of eight with comparisons indicated that Alzheimer's disease-like neuropathology
      was more likely to be found in the brains of patients with schizophrenia than in
      the brains of comparison subjects. CONCLUSIONS: Suggestions that cerebral plaques
      and neurofibrillary tangles are more common in schizophrenia in association with
      neuroleptic treatment were not supported.

PMID- 9167519
TI  - HIV infection among young adults with psychotic disorders.
AB  - OBJECTIVE: The authors examined HIV infection among young adults with newly
      diagnosed psychotic disorders. METHODS: The study was based on a research cohort
      of 320 first-admission patients aged 20-39 years in a semirural-suburban county.
      Research assessments and medical records were systematically reviewed for
      information about HIV status. RESULTS: Despite the fact that few patients were
      tested for HIV, 12 (3.8%) of the 320 patients had a known HIV infection. In all
      12 cases, the HIV infection was contracted before the onset of psychosis. AIDS
      was the leading cause of mortality in the 320 patients. CONCLUSIONS: The HIV
      epidemic may be having an important effect on the etiology and the course of
      psychotic disorders.

PMID- 9167520
TI  - Effect of prefrontal repetitive transcranial magnetic stimulation in obsessive
      compulsive disorder: a preliminary study.
AB  - OBJECTIVE: Prefrontal mechanisms are implicated in obsessive-compulsive disorder.
      The authors investigated whether prefrontal repetitive transcranial magnetic
      stimulation influenced obsessive-compulsive disorder symptoms. METHOD: Twelve
      patients with obsessive-compulsive disorder were given repetitive transcranial
      magnetic stimulation (80% motor threshold, 20 Hz/2 seconds per minute for 20
      minutes) to a right lateral prefrontal, a left lateral prefrontal, and a
      midoccipital (control) site on separate days, randomized. The patients' symptoms
      and mood were rated for 8 hours afterward. RESULTS: Compulsive urges decreased
      significantly for 8 hours after right lateral prefrontal repetitive transcranial
      magnetic stimulation, but there were nonsignificant increases in compulsive urges
      after repetitive transcranial magnetic stimulation of the midoccipital site. A
      shorter-lasting (30 minutes), modest, and nonsignificant reduction in compulsive
      urges occurred after left lateral prefrontal repetitive transcranial magnetic
      stimulation. Mood improved during and 30 minutes after right lateral prefrontal
      stimulation. CONCLUSIONS: These preliminary results suggest that right prefrontal
      repetitive transcranial magnetic stimulation might affect prefrontal mechanisms
      involved in obsessive-compulsive disorder.

PMID- 9167521
TI  - Sleep deprivation combined with consecutive sleep phase advance as a fast-acting
      therapy in depression: an open pilot trial in medicated and unmedicated patients.
AB  - OBJECTIVE: The authors' goal was to test the hypothesis that the antidepressant
      effect of total sleep deprivation can be maintained by initially avoiding sleep
      during a supposedly "critical" time period in the early morning. METHOD: They
      studied 33 inpatients with major depression, melancholic type, all of whom
      responded positively to total sleep deprivation. Twelve of the patients were men
      and 21 were women; their mean age was 46.7 years (SD = 13.7). After total sleep
      deprivation, the patients started a sleep schedule from 5:00 p.m. to 12:00
      midnight, which then was shifted back by 1 hour each day until a sleep time of
      11:00 p.m. to 6:00 a.m. was reached. RESULTS: Twenty (61%) of the 33 patients who
      responded to total sleep deprivation with an improved state of mood maintained
      this improvement during sleep phase advance therapy. Drug-free and medicated
      patients did not differ from each other. CONCLUSIONS: The rapid amelioration of
      mood observed with total sleep deprivation can be preserved with a succeeding
      phase shift of the sleep period.

PMID- 9167522
TI  - Fluoroquinolone inhibition of clozapine metabolism.

PMID- 9167523
TI  - Neuroleptic malignant syndrome following initiation of clozapine therapy.

PMID- 9167524
TI  - Diazepam-responsive neuroleptic malignant syndrome: a diagnostic subtype?

PMID- 9167525
TI  - Catatonia 20 years later.

PMID- 9167526
TI  - Vitamin C for paroxetine- and fluvoxamine-associated bleeding.

PMID- 9167527
TI  - Cyproheptadine: a potent in vivo serotonin antagonist.

PMID- 9167528
TI  - Telemedicine in Psychiatry: making the dream reality.

PMID- 9167529
TI  - Genetic heterogeneity in nocturnal enuresis.

PMID- 9167530
TI  - Religion index for psychiatric research.

PMID- 9167531
TI  - CO2 challenge in nonclinical subjects.

PMID- 9167532
TI  - Triplet repeat diseases in man, microbes, and molecules.

PMID- 9167533
TI  - Debating dissociative diagnoses.

PMID- 9167534
TI  - Biased book review.

PMID- 9167535
TI  - Homicidal behavior in drug abusing psychiatric patients.

PMID- 9167537
TI  - Festschrift in honor of Melvin Sabshin, M.D., Medical Director American
      Psychiatric Association, 1974-1997.

PMID- 9167536
TI  - Internet addiction, Internet psychotherapy.

PMID- 9167538
TI  - Melvin Sabshin: integrator, innovator, and master of metaphor.

PMID- 9167539
TI  - Toward a strategy for healthy adolescent development.
AB  - Mel Sabshin and I worked closely together during the 1950s, and his influence on
      me-as on so many others-has persisted ever since. I have never ceased to be
      deeply impressed by his intellectual curiosity, his strong sense of social
      responsibility, his integrative capacity across disciplines, and his constructive
      problem-solving orientation. One of his pioneering and enduring interests over
      several decades has been in the study of normality. Within that frame-work, he
      has devoted special attention to adolescent development. In this article I pick
      up on this strand of his interest. During much of my career, and especially
      during the past 14 years at the Carnegie Corporation, I have sought ways to build
      the knowledge base on adolescent development and put that knowledge to use in
      preventing lifelong casualties.

PMID- 9167541
TI  - The concept and boundaries of personality disorders.

PMID- 9167540
TI  - Normatology: a review and commentary with reference to abortion and physician
      assisted suicide.

PMID- 9167542
TI  - The panic-agoraphobic spectrum: a descriptive approach to the assessment and
      treatment of subtle symptoms.
AB  - OBJECTIVE: Psychiatric classification is still a topic of considerable discussion
      and debate in spite of major advances in the past two decades. The debate
      involves categorical versus dimensional approaches, cutoff numbers of symptoms to
      define a case, degree of impairment, objective diagnostic criteria versus more
      theoretically based criteria, episodic versus trait-like symptoms, and the role
      of atypical and subclinical symptoms. All of these issues have been raised for
      the anxiety disorders and depression. This article presents the conceptualization
      of a relatively novel and testable approach to the diagnosis and classification
      of panic and agoraphobia, the panic-agoraphobic spectrum, and pilot data on a new
      questionnaire to assess it. METHOD: Pilot testing of the Panic-Agoraphobic
      Spectrum Questionnaire was undertaken with 100 inpatients who had lifetime
      diagnoses of panic disorder, unipolar depression, comorbid panic and unipolar
      depressive disorders, or an eating disorder. The instrument emphasizes impairment
      related to 144 behaviors and experiences in seven panic-agoraphobic symptom
      domains. RESULTS: Patients with panic disorder scored highest on the
      questionnaire, and those with comorbid depression showed even greater severity of
      illness. The scores of the patients with eating disorders and of the depressed
      patients differed from those of the other groups but also differed from 0.
      CONCLUSIONS: The spectrum model of panic and agoraphobia is a flexible and
      comprehensive means of describing this clinical complex. The proposed model,
      complementary to the categorical approach, presumably expresses a unitary
      pathophysiology. Its usefulness is discussed in terms of its value for patient
      therapist communication, outcome measures, identification of subtle personality
      traits, and subtyping of patients for research and treatment.

PMID- 9167543
TI  - Cognitive deficit measures in schizophrenia: factor structure and clinical
      correlates.
AB  - OBJECTIVE: The authors aimed to delineate the "common denominators" across a
      representative number of cognitive measures by administering such measures to a
      large number of schizophrenic subjects. The authors also aimed to study the
      consistency of the subjects' performance over a 1-year period and to look into
      the relationship between cognitive task performance and clinical status. METHOD:
      One hundred fifty-seven schizophrenic subjects with a DSM-III-R diagnosis of
      schizophrenia were assessed under standardized testing conditions on the dichotic
      listening and shadowing task, the span of apprehension task, the simple reaction
      time tasks, the critical stimulus duration, and the interstimulus interval in
      which they would become free from the masking effect. The clinical status of the
      subjects was assessed during index assessment, and 97 subjects were reassessed at
      the end of 1 year. Forty-seven subjects were randomly selected for reassessment
      on the cognitive tasks administered 1 year earlier. The subjects' performance was
      compared to that of 56 nonschizophrenic patients with nasopharyngeal carcinoma
      who had undergone radiation therapy. RESULTS: The cognitive task scores were
      factor analyzed, giving five distinct factors made up of the span of apprehension
      accuracy scores, simple reaction time scores, shadowing accuracy scores, span of
      apprehension error scores, and susceptibility to interference scores. At index
      assessment, the subjects' shadowing accuracy and reaction time were significantly
      related to their quality of life, social adjustment, and positive symptoms. The
      subjects' span of apprehension scores were related to their negative symptoms,
      measured in terms of work and daily life functions. The initial relationship
      between the subjects' cognitive test scores and their outcome status remained
      consistent at follow-up. CONCLUSIONS: The documented cognitive deficits in
      schizophrenic patients probably reflect a more enduring trait-like status with
      correlations with outcome status. These results also indicate that the cognitive
      measures may be simplified in complexity without a corresponding reduction in
      their clinical significance.

PMID- 9167544
TI  - DSM-III and its reception: a European view.
AB  - The author analyzes some elements in the reception of DSM-III in Europe. The
      worldwide success of a diagnostic classification originally presented as a purely
      American endeavor is associated with recurrent, albeit not often openly
      formulated, criticisms. In the history of psychiatric nosologies, the purely
      descriptive phase was succeeded by a period during which theories were dominant,
      as in the Kraepelinian system. DSM-III originated in recognition of the existence
      in the United States of contending psychodynamic and psychosocial orientations
      and problems of communication, which became even more evident with the growth of
      psychopharmacology and the influence of the biological school. Whereas ICD
      offered compromise solutions, DSM-III used a new paradigm based on diagnostic
      categories and a multiaxial format, which were on the whole easily accepted. Most
      criticisms involved three points. The first was the atheoretical syndromic
      approach, seen as a regression and an expression of an American preference for
      superficial facts and contempt for psychopathology, which was considered in
      Europe the source of future progress. The second was the introduction of
      quantification, which was rejected by some in the name of the clinical tradition,
      which emphasized understanding of the individual case. The third was DSM-III's
      adherence to alleged American values, such as pragmatism and novelty. The
      ambivalence of Europeans toward the world expansion of American culture was
      reinforced by use of English as the language of international scientific
      communication. The mostly irrational nature of the criticisms contrasts sharply
      with the general acceptance of DSM-III and its successors, which rests on their
      objective merits.

PMID- 9167545
TI  - New perspectives in mental health services in Shanghai.
AB  - This article reports developments in mental health services in Shanghai during
      the past several years, including family education and involvement, new forms of
      community services, psychological consultation programs, hot line services and
      crisis intervention, dealing with psychological problems in general hospitals,
      and nursing care for elderly patients with dementia. The authors reevaluate and
      outline the new perspectives in mental health services in Shanghai.

PMID- 9167546
TI  - The Defeat Depression Campaign: psychiatry in the public arena.
AB  - OBJECTIVE: The adequate recognition and treatment of depression are inhibited by
      negative public attitudes and gaps in professional expertise. This paper
      describes the activities and efforts of the Defeat Depression Campaign, a joint
      activity of the Royal College of Psychiatrists and the Royal College of General
      Practitioners, in the United Kingdom. METHOD: A 5-year campaign was undertaken
      from 1992 to 1996, aimed at enhancing public awareness and attitudes and
      providing professional education. RESULTS: An informational media campaign
      directed toward the general public was successfully undertaken. Leaflets, books,
      and audiotapes were also prepared and distributed to the public.
      Multiprofessional conferences on specific aspects of depression were organized.
      An extensive program of general practice education included consensus conferences
      and statements, recognition and management guidelines, training videotapes, and
      other publications. Public attitudes were found to be relatively favorable,
      except attitudes toward antidepressants, which were viewed as addictive. A
      general consequence of the campaign was the development of much additional public
      material and professional education not directly originating from the campaign.
      Aspects of the campaign are being evaluated, including public attitude change,
      impact of educational materials on general practitioners, and prescription of
      antidepressants. CONCLUSIONS: A campaign of this kind serves a useful function in
      enhancing public education and awareness and improving professional recognition
      and management of depression.

PMID- 9167547
TI  - Psychiatry in the framework of primary health care: a threat or boost to
      psychiatry?

PMID- 9167548
TI  - Recent developments in American psychiatry and Dr. Melvin Sabshin's contributions
      to them.
AB  - A "Dialogue" session was set up during the seventh scientific meeting of the
      Pacific Rim College of Psychiatrists in 1995. The objective of this session was
      to clarify the opinions of great scholars on modern psychiatry and their
      contributions to its development. Participants discussed characteristics of
      psychiatry in various countries as well as the future of world psychiatry. The
      following article is the "dialogue" that occurred between Professor Nishizono and
      Dr. Melvin Sabshin.

PMID- 9167549
TI  - The future of medical education and teaching: a psychiatric perspective.

PMID- 9167550
TI  - Predicting academic performance of medical students: the first three years.
AB  - OBJECTIVE: The purpose of this exploratory study was to identify a cluster of
      variables that would most economically explain variations in the grade point
      averages of medical students during the first 3 years of study. METHOD: Data were
      derived from a study of 92 students admitted to the 3rd Faculty of Medicine in
      1992-1993 academic year and who were still in the medical school at the end of
      the sixth semester (third year). Stepwise regression analysis was used to build
      models for predicting log-transformed changes in grade point average after six
      semesters of study-at the end of the first, second, and third years. Predictor
      variables were chosen from four domains: 1) high school grade point averages in
      physics, mathematics, and the Czech language over 4 years of study, 2) results of
      admission tests in biology, chemistry, and physics, 3) admission committee's
      assessment of the applicant's ability to reproduce a text, motivation to study
      medicine, and social maturity, and 4) scores on the sentimentality and attachment
      scales of the Tridimensional Personality Questionnaire. RESULTS: The regression
      model, which included performance in high school physics, results of the
      admission test in physics, assessment of the applicant's motivation to study
      medicine, and attachment scale score, accounted for 32% of the change in grade
      point average over six semesters of study. The regression models using the first
      , second-, and third-year grade point averages as the dependent variables showed
      slightly decreasing amounts of explained variance toward the end of the third
      year of study and within domains, changing the structure of predictor variables.
      CONCLUSIONS: The results suggest that variables chosen from the assessment
      domains of high school performance, written entrance examination, admission
      interview, and personality traits may be significant predictors of academic
      success during the first 3 years of medical study.

PMID- 9167552
TI  - Valvular heart disease: putting guidelines into practice.

PMID- 9167551
TI  - Learning from asthma deaths.

PMID- 9167553
TI  - Antenatal HIV testing: what now?

PMID- 9167554
TI  - Helicobacter gastroduodenitis: a serious infectious disease.

PMID- 9167555
TI  - Sexual medicine.

PMID- 9167556
TI  - Preimplantation diagnosis is likely to increase in The Netherlands.

PMID- 9167557
TI  - Direct HIV testing of donated blood is inevitable.

PMID- 9167558
TI  - Age specific trends in asthma mortality in England and Wales, 1983-95: results of
      an observational study.
AB  - OBJECTIVE: To determine trends in asthma mortality by age group in England and
      Wales during 1983-95. DESIGN: Observational study. SETTING: England and Wales.
      SUBJECTS: All deaths classified as having an underlying cause of asthma
      registered from 1 January 1983 to 31 December 1995. MAIN OUTCOME MEASURE: Time
      trends for age specific asthma deaths. RESULTS: Deaths in the age group 5-14
      years showed an irregular downward trend during 1983-95; deaths in the age groups
      15-44, 45-64, and 65-74 years peaked before 1989 and then showed a downward
      trend; and deaths in the age group 75-84 years peaked between 1988 and 1993 and
      subsequently dropped. Trends were: age group 5-14 years, 6% (95% confidence
      interval 3% to 9%); 15-44 years, 6% (5% to 7%); 45-64 years, 5% (4% to 6%); 65-74
      years, 2% (1% to 3%). Deaths in the 75-84 and 85 and over categories plateaued.
      CONCLUSIONS: There are downward trends in asthma mortality in Britain, which may
      be due to increased use of prophylactic treatment.

PMID- 9167559
TI  - Effect of long-term treatment with salmeterol on asthma control: a double blind,
      randomised crossover study.
AB  - OBJECTIVES: To determine the effect of adding salmeterol 50 micrograms twice
      daily for six months to current treatment in subjects with asthma who control
      their inhaled corticosteroid dose according to a management plan. DESIGN: A
      double blind, randomised crossover study. SETTING: Nottingham. SUBJECTS: 101
      subjects with mild or moderate asthma taking at least 200 micrograms twice daily
      of beclomethasone dipropionate or budesonide. INTERVENTIONS: Salmeterol 50
      micrograms twice daily and placebo for six months each, with a one month washout.
      Subjects adjusted inhaled steroid dose according to guidelines. MAIN OUTCOME
      MEASURE: Reduction in inhaled steroid use, exacerbations of asthma, and use of
      oral steroids. RESULTS: Data were available for 87 subjects. When compared with
      placebo salmeterol treatment was associated with a 17% reduction in inhaled
      steroid use (95% confidence interval 12% to 22%) with no significant difference
      in the number of subjects who had an exacerbation (placebo 25%, salmeterol 16%)
      or use of oral steroids. For secondary end points salmeterol treatment was
      associated with higher morning and evening peak expiratory flow and forced
      expiratory volume in one second; a reduction in symptoms, bronchodilator use and
      airway responsiveness to methacholine; and no effect on serum potassium
      concentration, 24 hour heart rate, or the final forced expiratory volume in one
      second achieved during a salbutamol dose-response study. CONCLUSIONS: In subjects
      who adjusted their inhaled steroid treatment according to guidelines the addition
      of salmeterol 50 micrograms twice daily was associated with a reduction in
      inhaled steroid use and improved lung function and symptom control.

PMID- 9167560
TI  - Molecular investigation into outbreak of HIV in a Scottish prison.
AB  - OBJECTIVES: To support already established epidemiological links between inmates
      of Glenochil prison positive for HIV infection by using molecular techniques and
      thus provide evidence of the extent of acquisition during a recent outbreak of
      the disease resulting from needle sharing. To identify possible sources of the
      outbreak, and to demonstrate the ability of the methodology to make further links
      beyond the original outbreak. DESIGN: Viral sequences obtained from the blood of
      HIV positive prisoners previously identified by standard epidemiological methods
      were compared with each other and with sequences from other Scottish patients.
      SETTING: Glenochil prison for men, central Scotland. SUBJECTS: Adult inmates and
      their possible contacts. RESULTS: Phylogenetic analysis of viral sequences in two
      different genomic regions showed that 13 of the 14 HIV positive prisoners had
      been infected from a common source. Previous research had shown that six of these
      had acquired their infection in Glenochil; molecular evidence suggests that more
      than double this number were infected while incarcerated. Virus from two long
      term HIV positive patients who were in the prison at the time of the outbreak but
      who were not identified in the original or subsequent surveys was sufficiently
      different to make it unlikely that they were the source. A viral sequence from
      heterosexual transmission from one inmate showed the ability of these techniques
      to follow the infection through different routes of infection. CONCLUSION: The
      number of prisoners infected with HIV during the 1993 outbreak within Glenochil
      prison was more than twice that previously shown. This shows the potential for
      the spread of bloodborne diseases within prisons by injecting drugs.

PMID- 9167561
TI  - Residential and occupational exposure to sunlight and mortality from non
      Hodgkin's lymphoma: composite (threefold) case-control study.
AB  - OBJECTIVE: To determine whether non-Hodgkin's lymphoma mortality is associated
      with sunlight exposure. DESIGN: Three case-control studies based on death
      certificates of non-Hodgkin's lymphoma, melanoma, and skin cancer mortality
      examining associations with potential sunlight exposure from residence and
      occupation. SETTING: 24 states in the United States. SUBJECTS: All cases were
      deaths from non-Hodgkin's lymphoma, melanoma, and non-melanotic skin cancer
      between 1984 and 1991. Two age, sex, and race frequency matched controls per case
      were selected from non-cancer deaths. MAIN OUTCOME MEASURES: Odds ratios for non
      Hodgkin's lymphoma, melanoma, and skin cancer from residential and occupational
      sunlight exposure adjusted for age, sex, race, socioeconomic status, and farming
      occupation. RESULTS: Non-Hodgkin's lymphoma mortality was not positively
      associated with sunlight exposure based on residence. Both melanoma and skin
      cancer were positively associated with residential sunlight exposure. Adjusted
      odds ratios for residing in states with the highest sunlight exposure were 0.83
      (95% confidence interval 0.81 to 0.86) for non-Hodgkin's lymphoma, 1.12 (1.06 to
      1.19) for melanoma, and 1.30 (1.18 to 1.43) for skin cancer. In addition, non
      Hodgkin's lymphoma mortality was not positively associated with occupational
      sunlight exposure (odds ratio 0.88; 0.81 to 0.96). Skin cancer was slightly
      positively associated with occupational sunlight exposure (1.14; 0.96 to 1.36).
      CONCLUSIONS: Unlike skin cancer and to some extent melanoma, non-Hodgkin's
      lymphoma mortality was not positively associated with exposure to sunlight. The
      findings do not therefore support the hypothesis that sunlight exposure
      contributes to the rising rates of non-Hodgkin's lymphoma.

PMID- 9167562
TI  - Transfer of adults between intensive care units in the United Kingdom: postal
      survey.

PMID- 9167563
TI  - Chlamydia pneumoniae antibodies and serum lipids in Finnish men: cross sectional
      study.

PMID- 9167564
TI  - The effect of deprivation on variations in general practitioners' referral rates:
      a cross sectional study of computerised data on new medical and surgical
      outpatient referrals in Nottinghamshire.
AB  - OBJECTIVE: To determine the effect of deprivation on variations in general
      practitioners' referral rates using the Jarman underprivileged area (UPA(8))
      score as a proxy measure. DESIGN: Cross sectional survey of new medical and
      surgical referrals from general practices to hospitals (determined from hospital
      activity data). SETTING: All of the 183 general practices in Nottinghamshire and
      all of the 19 hospitals in Trent region. MAIN OUTCOME MEASURES: The relation
      between the referral rates per 1000 registered patients and the practice
      population's UPA(8) score (calculated on the basis of electoral ward), with
      adjustment for the number of partners, percentage of patients aged over 65 years,
      and fundholding status of each practice. RESULTS: There was a significant
      independent association between deprivation, as measured by the UPA(8) score, and
      high total referral rates and high medical referral rates (P < 0.0001). The
      UPA(8) score alone explained 23% of the total variation in total referral rates
      and 32% of the variation in medical referral rates. On multivariate analysis,
      where partnership size, fundholding status, and percentage of men and women aged
      over 65 years were included, the UPA(8) score explained 29% and 35% of the
      variation in total and medical referral rates respectively. CONCLUSION: Of the
      variables studied, the UPA(8) score was the strongest predictor of variations in
      referral rates. This association is most likely to be through a link with
      morbidity, although it could reflect differences in patients' perceptions,
      doctors' behaviour, or the use and provision of services.

PMID- 9167565
TI  - Cardiopulmonary resuscitation.

PMID- 9167566
TI  - Persistent itching due to etherified starch plasma expander.

PMID- 9167567
TI  - How to do it. Run a preparation course for postgraduate examinations.
AB  - This paper provides a practical guide to running preparation courses for
      postgraduate examinations and is based on the authors' experience. It is intended
      to be useful to organisers of proposed or existing courses as well as to
      potential users of courses--people in every specialty preparing for a
      postgraduate examination. The paper covers the practical aspects of staging and
      financing a course and recruiting tutors and attracting candidates, in addition
      to covering the structure, educational content, and evaluation of the course.

PMID- 9167568
TI  - Stress and the biology of inequality.
AB  - It is well established that health depends on socioeconomic circumstances, but
      the biology of this relation is not well described. Psychosocial factors
      operating throughout the life course, beginning in early life, influence a
      variety of biological variables. Research with non-human primates shows the
      effects of dominance hierarchy on biology, and similar metabolic differentials
      are evident in a hierarchy of white collar civil servants. The neuroendocrine
      "fight or flight" response produces physiological and metabolic alterations which
      parallel those observed with lower socioeconomic status. The biological effects
      of the psychosocial environment could explain health inequalities between
      relatively affluent groups.

PMID- 9167569
TI  - Informed consent in medical research. Doctors are arrogant to think they need to
      debate issue of patient consent.

PMID- 9167570
TI  - Informed consent in medical research. No one has a monopoly on deciding what is
      ethical.

PMID- 9167571
TI  - Informed consent in medical research. Let readers judge for themselves.

PMID- 9167572
TI  - Informed consent in medical research. Ethics committees and BMJ should continue
      to consider the overall benefit to patients.

PMID- 9167574
TI  - Informed consent in medical research. Clinicians are being disingenuous with
      themselves.

PMID- 9167573
TI  - Informed consent in medical research. Risk of bias may be another reason not to
      seek consent.

PMID- 9167575
TI  - Informed consent in medical research. We all have a responsibility to contribute
      to research.

PMID- 9167576
TI  - Informed consent in medical research. Minimum ethical standards should not vary
      among countries.

PMID- 9167577
TI  - Informed consent in medical research. South African study raises the ghosts of
      Nuremberg and apartheid.

PMID- 9167578
TI  - Informed consent in medical research. Consent is not always practical in
      emergency treatments.

PMID- 9167579
TI  - Informed consent in medical research. Children from the age of 5 should be
      presumed competent.

PMID- 9167580
TI  - Informed consent in medical research. Research in patients with mental
      retardation poses special problems.

PMID- 9167581
TI  - Informed consent in medical research. Studies with important conclusions but
      without patient consent should be published.

PMID- 9167582
TI  - Informed consent in medical research. Failure to publish completed randomised
      controlled trials is unethical in itself.

PMID- 9167583
TI  - Informed consent in medical research. Subjects may be coerced into participating
      in studies.

PMID- 9167584
TI  - Informed consent in medical research. The whole population must be mobilised in
      the war against cancer.

PMID- 9167585
TI  - Informed consent in medical research. Patients may not understand enough to give
      their informed consent.

PMID- 9167586
TI  - Informed consent in medical research. Communication with potential subjects needs
      to be effective.

PMID- 9167587
TI  - Informed consent in medical research. In routine practice the consent form is a
      request form and informed consent is informed choice.

PMID- 9167588
TI  - Reintroduction of medical officers of health would solve many problems.

PMID- 9167589
TI  - Many children remain unrestrained in cars.

PMID- 9167590
TI  - Solar ultraviolet radiation is not a major cause of primary cutaneous non
      Hodgkin's lymphoma.

PMID- 9167591
TI  - What is it acceptable to die of?

PMID- 9167592
TI  - Redback spider is now established in Japan: bites can be recognised by a unique
      sign.

PMID- 9167593
TI  - Segregated health statistics perpetuate racial stereotypes.

PMID- 9167594
TI  - Incidence of myocardial infarction is affected by deprivation in Buckinghamshire
      too.

PMID- 9167595
TI  - Project will assess effects of patients writing about their terminal illness on
      self perceived quality of life.

PMID- 9167596
TI  - South Asian diabetic patients need more education about their illness.

PMID- 9167597
TI  - Shorter preoperative fluid fasts reduce postoperative emesis.

PMID- 9167598
TI  - Pharmacists are key members of primary health care teams.

PMID- 9167599
TI  - Practice guideline for examination of the placenta: developed by the Placental
      Pathology Practice Guideline Development Task Force of the College of American
      Pathologists.
AB  - The Placental Pathology Practice Guideline Development Task Force, a
      multidisciplinary group, has prepared this guideline to assist those involved
      with placental examination. It provides recommendations related to indications
      and methods for placental examination as well as sample worksheets. An algorithm
      for the handling of placentas summarizes the recommendations of the guideline. A
      summary of specific findings of placental examination together with their
      pathogenesis and clinical associations is also provided. Recommendations related
      to reporting with sample reporting formats are included. The guideline is
      intended as an educational tool, and its use should be guided by the individual
      circumstances and care setting of specific cases.

PMID- 9167600
TI  - Stereotactic brain biopsies: specimen preparation and evaluation.
AB  - Stereotactically directed needle biopsy of central nervous system lesions is a
      widely used diagnostic procedure with low morbidity and mortality. Diagnostic
      tissue is obtained in most instances. As a part of the College of American
      Pathologists Practical Topics in Neuropathology series, the following report
      summarizes the pathologist's role in the procurement, preparation, and
      interpretation of these important specimens.

PMID- 9167601
TI  - Frozen section evaluation of stereotactic brain biopsies: diagnostic yield at the
      stereotactic target position in 188 cases.
AB  - OBJECTIVE: Use of the image-guided stereotactic brain biopsy has facilitated the
      diagnosis of previously inaccessible lesions with both safety and reliability.
      However, few studies have assessed the diagnostic yield of frozen section
      evaluation of the initial stereotactic target (FS-0). We describe our experience
      with 188 stereotactic brain biopsies in order to evaluate the diagnostic yield of
      FS-0. DESIGN: Retrospective study of 188 stereotactic brain biopsies from 185
      patients. SETTING: Tertiary referral center with a high volume of neurosurgical
      cases including image-guided stereotactic brain biopsies. PATIENTS: One hundred
      eighty-five patients who underwent imaged-guided stereotactic brain biopsy over a
      58-month period. RESULTS: The patients studied included 107 males and 78 females
      (mean age 48 years). Eleven (6%) biopsies were nondiagnostic. Diagnoses from FS-0
      included a neoplastic condition in 96 (73%) of 131 cases and a nonneoplastic
      condition in 23 (50%) of 46 cases. In 119 (67%) of 177 cases, a diagnosis was
      reached at FS-0. A correct diagnosis was made on subsequent frozen section in 28
      (16%) of cases, including 21 (16%) of 131 neoplasms and 7 (15%) of nonneoplastic
      conditions. In 15 (54%) of 28 cases, the correct diagnosis was made on the second
      frozen section; in 25 (89%) of 28, the correct diagnosis was made by the fourth
      frozen section. In 14 (11%) of 131 neoplastic cases, a sampling error relative to
      the lesion resulted in an inaccurate diagnosis at FS-0. A significant error in
      diagnosis occurred in three cases (1.7%). CONCLUSIONS: We conclude that (1)
      because 58 (33%) of 177 diagnosed cases in our series would have been potentially
      misdiagnosed if only one biopsy had been taken at the stereotactic target, frozen
      section evaluation or cytologic examination of material at the time of surgery
      should be performed routinely to ensure that adequate tissue has been obtained
      for purposes of diagnosis; (2) taking up to four biopsies increases the
      diagnostic yield (from 67% to 89% in this series); and (3) neoplastic lesions are
      more likely to be definitively diagnosed at FS-0 than non-neoplastic lesions.

PMID- 9167602
TI  - Malignant supratentorial glial-neuronal neoplasms: report of two cases and review
      of the literature.
AB  - OBJECTIVE: Malignant neoplasms exhibiting mixed populations of neuronal and glial
      cells occurring in the cerebral hemispheres of young adults and children are well
      recognized, but rare. A confusing array of diagnostic terms has arisen. We
      describe two patients with such tumors and review the literature concerning these
      interesting cases. PATIENTS: A 21-year-old man and a 5-year-old girl presented
      with large, cystic, intracerebral lesions on magnetic resonance images, which
      proved to be composite neoplasms exhibiting malignant neurons and astrocytes.
      RESULTS: The 21-year-old man had a frontal lobe mass with enhancing and
      nonenhancing regions, which corresponded to cerebral neuroblastoma and anaplastic
      astrocytoma, respectively. The presence of occasional microtubules and rare
      primitive presynaptic processes, accompanied by antisynaptophysin
      immunoreactivity, established the neuronal nature of the cells in the enhancing
      region. The nonenhancing region was composed of a moderately cellular neoplasm of
      fibrillar astrocytes that were mitotically active. The 5-year-old girl presented
      with a left parietal lobe neoplasm, which histologically was composed of lobular
      proliferations of neuroblasts and glia. The neuroblastic populations exhibited
      evidence of maturation with small anaplastic cells, spindle-shaped cells, and
      large dysmorphic ganglion cells. The glial tumor showed both well-differentiated
      fibrillary astrocytes with microcysts and anaplastic populations with central
      necrosis and pseudopalisading. CONCLUSIONS: Present classification systems
      devised to describe mixed neuronal and glial tumors do not adequately encompass
      the diversity of morphologies presented by these two cases. We conclude that the
      terms cerebral neuroblastoma-anaplastic astrocytoma for case 1 and cerebral
      ganglioneuroblastoma-glioblastoma for case 2 are preferred because they convey
      useful clinical information by reflecting concepts already encompassed by the
      World Health Organization's classification system of tumors of the central
      nervous system.

PMID- 9167603
TI  - Familial aggregation of soft tissue sarcomas: a report of three cases from a Li
      Fraumeni-like family.
AB  - Three rare cases of familial aggregation of soft tissue sarcomas (malignant
      fibrous histiocytoma in a mother and liposarcomas in her two children) are
      described. The mother developed a late onset of malignant fibrous histiocytoma in
      her right thigh. Her son and daughter both developed retroperitoneal liposarcomas
      at the ages of 38 and 33 years, respectively. The mother also developed gastric
      carcinoma as a second malignancy after a 2-year interval. These clinical features
      closely resemble those of Li-Fraumeni syndrome, but do not fulfill the exact
      diagnostic criteria. Genetically, the germline mutation of the p53 gene between
      exons 4 and 9 was not detected by sequencing DNA obtained from the peripheral
      blood of the mother. Immunohistochemically, p53 protein was found only in the
      liposarcoma of the daughter. These results strongly suggest that this familial
      aggregation of soft tissue sarcomas is very rare, and that it is a unique feature
      of a familial cancer syndrome that to our knowledge has not been defined or
      described previously.

PMID- 9167604
TI  - Teratomas in infancy and childhood at Tygerberg Hospital, South Africa, 1973 to
      1992.
AB  - OBJECTIVES: To document the childhood teratomas at Tygerberg Hospital and compare
      the profile with other African series. DESIGN: Retrospective review of the
      clinicopathologic features of 43 cases of childhood teratomas. Tumors were
      classified according to the World Health Organization criteria for germ cell
      tumors. SETTING: Tygerberg Hospital, University of Stellenbosch, Cape Town, South
      Africa. RESULTS: There were 26 mature, 15 immature, and 2 malignant teratomas.
      The most common sites were the ovaries and the sacrococcygeal region. Testicular
      teratomas were absent. The female-to-male ratio for black patients was 5.5:1.
      There was a peak age incidence in the first 4 years of life, with sacrococcygeal
      teratomas predominating. A second, smaller peak between 12 and 15 years was seen
      owing to ovarian teratomas. Immature teratomas presented at an earlier age than
      mature teratomas. The majority of ovarian teratomas occurred in patients of mixed
      race, whereas the extragonadal teratomas were distributed more evenly among the
      race groups. In black patients and patients of mixed race mature teratomas
      predominated, whereas in white patients immature teratomas were most common.
      CONCLUSIONS: The increased occurrence of teratomas among female patients, the
      large number of ovarian teratomas, the absence of testicular teratomas, and the
      low incidence of malignant teratomas correspond to the observations of other
      African series. Certain differences are apparent among the three race groups,
      namely, a high ratio of female-to-male patients in the black group, a
      predominance of ovarian teratomas in the mixed-race and black groups, and a
      predominance of extragonadal and immature teratomas in the white group.

PMID- 9167605
TI  - Reduction in blood culture contamination rate by feedback to phlebotomists.
AB  - OBJECTIVE: To determine whether monitoring and feedback of blood culture
      contamination rates to phlebotomists would reduce the overall contamination rate.
      DESIGN: Before and after interventional study. SETTING: Blood cultures collected
      by venipuncture by phlebotomists at Foothills Hospital, Calgary, a tertiary care
      teaching hospital. INTERVENTION: Feedback of contamination rates calculated from
      a laboratory definition of blood culture contamination. The definition was based
      on isolation of typical skin organisms from a single blood sample when two
      samples were obtained. MAIN OUTCOME MEASURE: Reduction in the laboratory-defined
      contamination rate in the second year. RESULTS: Of 8462 cultures collected by
      phlebotomists in the prefeedback year, 224 (2.6%) were contaminated, compared to
      131 (1.4%) of 9282 cultures in the postfeedback year. There was a rise in the
      total number of positive cultures regarded as significant but a fall in the
      number of coagulase-negative staphylococci that were regarded as significant by
      our definition. The rate of contamination in blood cultures collected by
      nonphlebotomists did not change. CONCLUSIONS: The contamination rate decreased
      after feedback. Our definition of contamination was imperfect and could be
      improved, but it was valuable in achieving a real reduction in blood culture
      contamination.

PMID- 9167606
TI  - Maternal melanoma metastatic to the placenta: a case report and review of the
      literature.
AB  - Metastases of maternal cancer to the placenta and fetus are rare in cases of
      maternal primary malignancy. This report describes a case of malignant melanoma
      metastatic to the placenta, reviews the literature, and discusses the clinical
      significance. A 33-year-old woman presented at 30 weeks' gestation with multiple
      metastases from a malignant melanoma diagnosed 4 years previously. Rapid maternal
      deterioration necessitated premature cesarean delivery, and maternal death
      occurred 7 days later. The placenta showed multiple metastases of malignant
      melanoma. The infant, however, is alive and well at 7 months of age. Melanoma in
      pregnancy rarely results in metastasis to the conceptus, but when it does occur
      there may be fatal consequences to the fetus. Therefore, the placenta should be
      thoroughly examined for metastasis, which, if present, should alert the clinician
      to monitor the infant for development of malignant disease.

PMID- 9167607
TI  - Desmoid tumor of the vulva associated with pregnancy.
AB  - Extra-abdominal desmoid tumor is a locally aggressive neoplasm that occurs most
      commonly in the pelvic or shoulder region in the third or fourth decade. We have
      identified one previously reported case of primary desmoid tumor of the vulva.
      Herein, we describe another case and, to our knowledge, the first reported case
      of vulvar desmoid tumor associated with pregnancy.

PMID- 9167608
TI  - Paraganglion of the prostate in a needle biopsy: a potential diagnostic pitfall.
AB  - Paraganglionic tissue incidentally observed in a needle biopsy of the prostate is
      reported. The tissue was seen in the periprostatic adipose tissue obtained during
      a needle biopsy of the prostate of an 81-year-old man. The paraganglionic cells
      demonstrated round to oval nuclei and basophilic granular or vacuolated cytoplasm
      and were immunohistochemically positive for chromogranin A, but negative for
      prostatic acid phosphatase and prostate-specific antigen. Paraganglion in the
      periprostatic adipose tissue is a diagnostic pitfall and should be distinguished
      from extension of prostatic adenocarcinoma outside the prostatic capsule into the
      periprostatic adipose tissue.

PMID- 9167609
TI  - Malignant melanoma of the lacrimal sac with surrounding melanosis.
AB  - Primary malignant melanomas of the lacrimal sac are extremely rare. In this
      report, the histologic findings of primary malignant melanoma of the lacrimal sac
      with surrounding melanosis are presented. Histologically, the surrounding
      melanosis showed radial proliferation of atypical melanocytes along the mucosal
      epithelium. Although we came to no firm conclusion as to whether the malignant
      melanoma in the present case was preceded by melanosis (radial proliferation of
      atypical melanocytes), to our knowledge this is the first description of lacrimal
      sac malignant melanoma associated with a lesion of this kind in the surrounding
      epithelium.

PMID- 9167610
TI  - Trilineage extramedullary myeloid cell tumor in myelodysplastic syndrome.
AB  - A patient with a 17-month history of myelodysplastic syndrome (refractory anemia
      with excess blasts that evolved into chronic myelomonocytic leukemia), which was
      treated with transfusions and erythropoietin, developed abdominal and inguinal
      lymphadenopathy. Biopsies of the abdominal nodes revealed virtual obliteration of
      the architecture by myeloid blasts admixed with maturing granulocytic, erythroid,
      and megakaryocytic precursors. The lymph node findings appeared to represent
      extramedullary dyshematopoiesis undergoing a tissue phase blast transformation.
      Four months later, the patient developed rising peripheral blast counts
      consistent with acute leukemia. Although the development of granulocytic sarcoma
      (also called extramedullary myeloid cell tumor) is well known to occur in
      patients with myelodysplastic syndromes, to our knowledge this is the first
      description of an extramedullary myeloid cell tumor associated with trilineage
      differentiation.

PMID- 9167611
TI  - Leukemic meningitis complicating early stage chronic lymphocytic leukemia.
AB  - Central nervous system involvement in chronic lymphocytic leukemia is rare. We
      describe a patient with early stage chronic lymphocytic leukemia who developed
      visual loss and transient paresthesias. Lumbar puncture with cytology and flow
      cytometry documented leukemic meningitis, which responded to standard treatment;
      including cranial irradiation and intrathecal chemotherapy. We review the
      literature of all previously reported cases of brain or meningeal involvement by
      chronic lymphocytic leukemia and suggest that this complication may frequently go
      unrecognized.

PMID- 9167612
TI  - Primary Hodgkin's disease of the sigmoid colon: a case report and review of the
      literature.
AB  - We report the case of an 81-year-old man who underwent a segmental resection of
      the sigmoid colon for severe diverticular disease. Histopathologic diagnosis
      revealed extranodal Hodgkin's disease, and the diagnosis was confirmed by
      immunohistochemistry. The incidence of extranodal Hodgkin's disease is rare and
      represents an infrequent occurrence as a gastrointestinal neoplasm and primary
      gastrointestinal lymphoma. A review of the literature for gastrointestinal
      lymphomas with emphasis on the occurrence of Hodgkin's disease, the diagnostic
      features, and the site of gastrointestinal tract involvement is reported.

PMID- 9167613
TI  - Anaplastic carcinoma occurring in association with a mucinous cystic neoplasm of
      the pancreas.
AB  - Anaplastic carcinomas of the pancreas are considered variants of ductal
      adenocarcinoma. They typically occur in elderly men. They have rarely been
      reported to occur in association with mucinous cystic neoplasms of the pancreas.
      We report a case of anaplastic carcinoma occurring in association with a
      pancreatic mucinous cystic neoplasm, borderline-type, in a 25-year-old woman who
      presented with lymph node and hepatic metastases.

PMID- 9167615
TI  - Short bowel syndrome: new therapeutic approaches.

PMID- 9167614
TI  - The College of American Pathologists, 1946-1996: laboratory standards.

PMID- 9167616
TI  - Scientific credibility requires complete presentation of methods.

PMID- 9167617
TI  - Differential regulation of type-II and type-X collagen synthesis by parathyroid
      hormone-related protein in chick growth-plate chondrocytes.
AB  - Parathyroid hormone-related protein is a critical autocrine regulator of
      endochondral ossification in the growth plate, as demonstrated by the severe
      disruption of growth-plate structure and function in parathyroid hormone-related
      protein-deficient transgenic mice. In the present study, the effects of
      parathyroid hormone-related protein on the synthesis of collagen mRNA and protein
      were studied in short-term cultures of isolated chick growth-plate chondrocytes.
      Parathyroid hormone-related protein selectively inhibits type-X collagen protein
      synthesis with no significant effect on type-II collagen protein synthesis. These
      effects were present in all maturationally distinct populations of chondrocytes
      separated by countercurrent centrifugal elutriation. In cultures of resting
      chondrocytes, the onset of type-X collagen expression was inhibited, while the
      synthesis of type-X collagen was decreased in cultures of hypertrophic
      chondrocytes. Synthesis of type-II and type-X collagen mRNA was examined by
      nonradioactive in situ hybridization with synthetic oligonucleotide cDNA probes,
      and the level of expression was quantified using digital image analysis. Dose
      dependent suppression of type-X collagen gene expression by parathyroid hormone
      related protein was observed, with no significant effect on type-II collagen mRNA
      detected. The results were confirmed by analysis of Northern blots of total
      chondrocyte mRNA. These experiments demonstrated differential transcriptional
      regulation of type-II and type-X collagen, with selective suppression of type-X
      collagen expression, by parathyroid hormone-related protein in growth-plate
      chondrocytes. In addition, excellent agreement was found between traditional
      protein and mRNA analyses and microscopic digital image analysis techniques,
      supporting the use of this convenient and sensitive assay method. Parathyroid
      hormone-related protein inhibits chondrocyte maturation and is known to stimulate
      proliferation, suggesting that this autocrine factor may function to regulate
      premature hypertrophy in the growth plate.

PMID- 9167618
TI  - Expression of parathyroid hormone-related peptide in human osteoarthritis.
AB  - To evaluate the involvement of the expression of parathyroid hormone-related
      peptide gene in human articular cartilage pathology, we performed
      immunohistochemical staining and in situ hybridization on specimens of femoral
      head cartilage obtained from 15 patients with osteoarthritis, 11 with rheumatoid
      arthritis, and 12 control subjects. Parathyroid hormone-related peptide-positive
      chondrocytes were observed predominantly in degenerated lesions of osteoarthritic
      tissue and were less evident in rheumatoid arthritic samples, while the normal
      cartilage expressed little parathyroid hormone-related peptide. In addition, the
      level of parathyroid hormone-related peptide expression was clearly dependent on
      the degree of cartilage degeneration; cartilage tissues with moderate
      degenerative changes contained more positive chondrocytes compared with mildly or
      severely degenerated cartilage. In situ hybridization confirmed the localization
      of parathyroid hormone-related peptide protein and demonstrated intense
      expression of mRNA of the peptide in osteoarthritic samples. This is the first
      demonstration of parathyroid hormone-related peptide expression in chondrocytes
      from pathologic articular cartilage of humans. Our results suggest that
      parathyroid hormone-related peptide may be involved in the pathophysiology of
      osteoarthritis.

PMID- 9167619
TI  - Compressive strains at physiological frequencies influence the metabolism of
      chondrocytes seeded in agarose.
AB  - Articular cartilage is subjected to dynamic compressive loading that is known to
      influence chondrocyte metabolism. While the exact signalling mechanisms are
      unclear, it has been proposed that cell deformation plays a role and may
      stimulate a metabolic response through distinctive pathways. In this study, a
      well characterized model system in which chondrocytes are embedded in agarose was
      used to study the effect of dynamic cellular strain on three key metabolic
      processes, namely the synthesis of glycosaminoglycan, of DNA, and of total
      protein. Using a specially designed apparatus, 15% compressive strain amplitude
      was applied to agarose-chondrocyte cylinders statically or dynamically over a
      range of frequencies (0.3-3 Hz). Static and low-frequency strain (0.3 Hz)
      inhibited the synthesis of glycosaminoglycan, while a frequency of 1 Hz
      stimulated synthesis. Static strain reduced the level of thymidine uptake,
      whereas dynamic strain at all frequencies induced an increase in chondrocyte
      proliferation. Incorporation of tritiated proline was suppressed by all strain
      regimens tested. The three parameters investigated were each influenced by the
      dynamic strain regimens in a distinct manner, implying that the signalling
      mechanisms involved are uncoupled.

PMID- 9167620
TI  - Chondrocyte biosynthesis correlates with local tissue strain in statically
      compressed adult articular cartilage.
AB  - In this study, we investigated the depth-dependent metabolic and structural
      responses of adult articular cartilage to large-strain, static, unconfined
      compression. Changes in cell biosynthetic activity and several morphometry-based
      structural parameters (cell density, cell volume fraction, cell surface-area
      density, mean cell surface area, and mean cell volume) were measured at eight
      sites representing different depth-zones between the articular surface and the
      cartilage/bone border. In addition, local axial strain in the superficial,
      transitional, upper radial, and lower radial zones was estimated on the basis of
      the change in cell density values. Static compression of articular cartilage
      revealed a highly heterogeneous deformation profile through the depth of the
      sample as well as zone-specific changes in biosynthetic activity, as reflected by
      incorporation of [3H]proline. The axial strains in the top layers were greater
      than the applied surface-to-surface strain, whereas axial strains adjacent to the
      cartilage/bone border were significantly less than the applied strain. Zonal
      changes in cell density and axial strain that occurred during static compression
      correlated well with alterations in metabolic activity. These coordinated changes
      between cell biosynthesis and cartilage structure suggest that zone-specific
      variations in mechanical stimuli could be responsible for spatially varied
      patterns of cartilage metabolic activity under load.

PMID- 9167621
TI  - Physical properties of rabbit articular cartilage after transection of the
      anterior cruciate ligament.
AB  - The effect of unilateral transection of the anterior cruciate ligament on the
      confined compression and swelling properties of the distal femoral articular
      cartilage of skeletally mature rabbits at 9 weeks after surgery was determined.
      Gross morphological grading of the transected and contralateral control distal
      femora stained with India ink confirmed that cartilage degeneration had been
      induced by ligament transection. Osteochondral cores, 1.8 mm in diameter, were
      harvested from the medial femoral condyles. The modulus, permeability, and
      electrokinetic (streaming potential) coefficient of the articular cartilage of
      the osteochondral cores were assessed by confined compression creep experiments.
      The properties (mean +/- SD) of control cartilage were: confined compression
      modulus, 0.75 +/- 0.28 MPa; hydraulic permeability, 0.63 +/- 0.28 x 10(-15)
      m2/Pa*sec; and electrokinetic coefficient, 0.16 +/- 0.31 x 10(-9) V/Pa. In
      transected knees, the modulus was reduced by 18% (p = 0.04), while the
      permeability and electrokinetic coefficient were not detectably altered. The
      change in modulus was accompanied by a trend (p = 0.07) toward a decrease (-11%)
      in the glycosaminoglycan density within the tissue, a significant increase (p <
      0.001) in the water content of the cartilage after equilibration in 1 x phosphate
      buffered saline from 70.3 +/- 4.1% in control knees to 75.2 +/- 4.0% in
      transected knees, and little further swelling after tissue equilibration in
      hypotonic saline. The compressive modulus of the cartilage from both control and
      transected knees was positively correlated with the density of tissue
      glycosaminoglycan. The alterations in the physical properties of the articular
      cartilage after transection of the anterior cruciate ligament in the rabbit show
      trends similar to those observed in human and other animal models of
      osteoarthritis and provide further support for the use of this model in the study
      of cartilage degeneration.

PMID- 9167622
TI  - Calcium-mobilizing purine receptors on the surface of mammalian articular
      chondrocytes.
AB  - If we are to fully understand mechanisms of cartilage homeostasis, it is
      essential that we know the full catalogue of receptors present on the surface of
      a chondrocyte and the pathways regulated by ligands that bind to these receptors.
      In this study, we describe chondrocyte responses to adenosine 5'-triphosphate and
      related molecules. Adenosine 5'-triphosphate stimulated a statistically
      significant, dose-dependent, transient rise in the concentration of calcium ions
      in Fura 2-loaded, differentiated, primary chondrocytes. The increase occurred in
      the absence of extracellular calcium, indicating a mobilization from
      intracellular stores. The increase in concentration of cytoplasmic calcium ions
      induced by adenosine 5'-triphosphate was mimicked by uridine 5'-triphosphate but
      not by 2-methylthioadenosine 5'-triphosphate, cytidine 5'-triphosphate, or
      adenosine. Heterologous desensitization experiments demonstrated that
      chondrocytes showed no subsequent response to uridine 5'-triphosphate after
      initial stimulation with adenosine 5'-triphosphate nor did they respond to
      adenosine 5'-triphosphate in inverse conditions, thereby indicating competition
      for the same receptor site. Together, these results are consistent with the
      presence of a P2U receptor on the cell surface of chondrocytes. Purine-induced
      calcium mobilization in passaged chondrocytes showed the same pharmacological
      profile with respect to agonist sensitivity, but responses were of greater
      magnitude than responses in primary differentiated chondrocytes, suggesting
      upregulation of the receptor with time in culture. Adenosine 5'-triphosphate and
      uridine 5'-triphosphate (1-100 microM) did not alter cartilage matrix synthesis
      as measured by rate of incorporation of [35S]sulfate into glycosaminoglycan by
      cartilage explants or primary chondrocytes. Matrix degradation, measured by
      release of glycosaminoglycan from cartilage explants, was also unaltered by
      adenosine 5'-triphosphate or uridine 5'-triphosphate (1-100 microM). Production
      of prostaglandin E2 was upregulated by incubation with either adenosine 5'
      triphosphate or uridine 5'-triphosphate. These data demonstrate the presence of a
      functional P2U-like purine receptor on the surface of primary articular
      chondrocytes and support the hypothesis that altered concentrations of
      extracellular purines may influence chondrocyte metabolism.

PMID- 9167623
TI  - Glycosaminoglycans and proteoglycans from different zones of the porcine knee
      meniscus.
AB  - Medial and lateral knee menisci were obtained from 20-week-old pigs, dissected
      into three zones of equal width, and analyzed for collagen and glycosaminoglycan
      content and for types of glycosaminoglycan and proteoglycan. The thin inner zones
      contained about 76% collagen and 8% glycosaminoglycan (by dry weight) and the
      outer zones, 93% collagen and 2% glycosaminoglycan. The most abundant
      glycosaminoglycan in all zones was chondroitin sulphate, accounting for about 80%
      of total glycosaminoglycan in the inner zones and 50-56% in the outer zones.
      Dermatan sulphate was the second most abundant glycosaminoglycan, present
      relative to chondroitin sulphate in a ratio of about 1:5-6 in the inner zones and
      1:1.5 in the outer zones. Hyaluronic acid accounted for 4-5% of total
      glycosaminoglycan content in the inner zones and 10% in the outer zones. All
      compositional parameters for the middle zones were between those for the inner
      and outer zones. There were no statistically significant differences in
      composition between medial and lateral menisci. Proteoglycans were extracted and
      separated into two groups (large and small proteoglycans) by gel chromatography
      and were further characterized by gel electrophoresis. The large proteoglycans
      stained with use of monoclonal antibodies to chondroitin sulphate and keratan
      sulphate. Biglycan and decorin, two related dermatan sulphate proteoglycans, were
      identified in the small proteoglycan pool by their behaviour on gel
      electrophoresis and by immunostaining with specific antibodies. In the middle and
      inner zones, biglycan predominated. The observed lower electophoretic mobilities
      of dermatan sulphate proteoglycans from the inner zone compared with those from
      the outer zone were explained by the discovery of longer dermatan sulphate chains
      on the former. Collectively, these results show that the extracellular matrix of
      knee meniscus varies continuously across its width in a manner consistent with
      increased compressive loading on the thinner, inside aspect of the structure.

PMID- 9167624
TI  - Rat model of distraction osteogenesis.
AB  - Prior studies of distraction osteogenesis in dog and rabbit models have shown
      predominantly intramembranous bone formation. Other models of fracture healing
      normally display mixtures of both endochondral and intramembranous bone
      formation. We have established a rat model of tibial lengthening that reliably
      reproduces the pattern of zonal osteogenesis previously observed in dog and
      rabbit models. A distraction rate of 0.25 mm twice a day with a 0-day latency
      period produced intramembranous bone with zones of progressive mineralization
      from collagen. With this protocol, rats bridged the distraction gap with a 25%
      increase in the tibial bone length. After 20 days of distraction and 50 days of
      consolidation, the three-point bending stiffness, as a percentage of the
      contralateral control, reached a level equivalent to that measured in the canine
      model for a 15% lengthening (28-day distraction and 84-day consolidation).
      Radiodensitometric analysis of the regenerate bones measured 97% of the
      unaffected contralateral tibial densities, and mineral analyses demonstrated that
      calcium and phosphorus levels in the regenerate bone reached 78% of contralateral
      tibial levels by day 70. We concluded that a rat model of distraction
      osteogenesis will be useful for a wide range of studies involving rapid
      intramembranous bone formation.

PMID- 9167625
TI  - Limb lengthening promotes muscle growth.
AB  - Studies of limb lengthening have demonstrated successful bone formation in the
      distraction gap. Failure of the muscle units to lengthen leads to many
      complications that significantly limit the success of this approach; it is,
      therefore, of paramount importance to characterize the behavior of the muscle
      during limb lengthening. In this study, tibiae of adult rabbits were lengthened
      for 10 days at a rate of 1 mm/day. The proliferative ability of the lengthened
      muscle was characterized using bromodeoxyuridine, a thymidine analogue that is
      incorporated during cell division, and desmin, a muscle-specific marker. We
      observed a large number of proliferating cells, specifically in the lengthened
      muscle, that were co-localized with many desmin-positive cells. The presence of
      bromodeoxyuridine nuclei inside desmin-positive muscle fibers suggests that limb
      lengthening promotes muscle growth by triggering myoblast proliferation and
      fusion into the lengthened muscle. Our findings are consistent with those of
      other studies in the reviewed literature that also suggest that limb lengthening
      promotes muscle growth.

PMID- 9167626
TI  - Topical application of nerve growth factor improves fracture healing in rats.
AB  - The aim of the present study was to examine the effects of nerve growth factor on
      the healing of unsplinted fractured ribs. After fracture of a rib in male rats,
      nerve growth factor was delivered by a miniosmotic pump to the fracture site for
      7 days at the rate of 1.4 micrograms/day. Callus catecholamine concentrations,
      bone callus size, histomorphometry, and biomechanical properties of the repairing
      rib were measured at 7, 21, and 42 days after fracture. After 21 days,
      concentrations of norepinephrine and epinephrine were significantly increased in
      the group treated with nerve growth factor compared with those in the control
      group (211% norepinephrine and 322% epinephrine). Also, the midline longitudinal
      area of non-osseous (fibrous tissue and cartilage) callus of the fracture was
      significantly smaller (54%) and had a higher proportion of cartilage in the
      treated group than in the controls. By 42 days, there was only bony callus
      between the fracture ends in both the control group and the treated group. The
      treated group, however, again showed significantly elevated concentrations of
      norepinephrine and epinephrine (286 and 382%, respectively) and significantly
      elevated breaking stress (50%) and Young's modulus (51%), together with a
      reduction in the transverse cross-sectional area of the repair site (57%). The
      resultant increases in effectiveness and rate of repair of bone with
      administration of nerve growth factor suggest that it may play an important role
      in the healing processes of fractured bone.

PMID- 9167627
TI  - Calcitonin gene-related peptide and reperfusion injury.
AB  - Calcitonin gene-related peptide is a potent intrinsic vasodilator, can induce
      prostacyclin release, and may inhibit membrane lipid peroxidation. This study
      examines the effect of calcitonin gene-related peptide on vessel diameters,
      capillary perfusion, and contractile function of skeletal muscle after 4 or 5
      hours of ischemia and during immediate reperfusion using the rat cremaster muscle
      model. Forty-two male rats were used; half of these received 0.2 ml of 10(-7) M
      calcitonin gene-related peptide after 0, 15, and 30 minutes of reperfusion, while
      the other half received normal saline as a control. By means of intravital
      videomicroscopy, the diameters of 10 vessels per muscle were measured prior to
      ischemia and during reperfusion. The fluorescein filling area was determined at
      15, 30, and 60 minutes of reperfusion. After 1 hour of reperfusion, muscle
      function was examined in vitro by quantifying the contractile response to
      electric field stimulation of the muscles in an organ bath system. There was a
      significant increase in the diameter of the arterioles, but not the small
      arteries, at every time point from 10 to 60 minutes of reperfusion. The
      fluorescein filling area was increased in treated muscles at every time point.
      Contractile function was not significantly preserved. In light of the ability of
      calcitonin gene-related peptide to relieve vasospasm and improve capillary
      perfusion, it may be useful in reducing reperfusion injury in the future.

PMID- 9167628
TI  - Treatment of experimental osteomyelitis by surgical debridement and the
      implantation of bioerodable, polyanhydride-gentamicin beads.
AB  - Osteomyelitis was induced in the radius in 77 rabbits and confirmed by
      histological examination and culture. At 4 weeks, the wounds were debrided and
      the animals were treated with (a) fatty acid dimer-sebacic acid beads (a
      bioerodable composite) impregnated with 20% or (b) 10% gentamicin sulfate, (c)
      placebo beads and intramuscular gentamicin sulfate, (d) placebo beads alone, or
      (e) debridement only. After 4 weeks, eradication of infection was determined by
      histological examination and culture. Osteomyelitis was eradicated in 93% of the
      animals treated with the beads and 20% gentamicin, in 67% of those treated with
      the beads and 10% gentamicin, in 25% of those treated with placebo beads and
      intramuscular gentamicin, in 7% of those treated with placebo beads alone, and in
      12.5% of those treated with debridement only (p values from < 0.001 to 0.02).
      Fatty acid dimer-sebacic acid beads with gentamicin were then implanted in
      noninfected rabbits, and gentamicin sulfate concentrations in bone, serum, urine,
      and wound exudate were measured. Gentamicin sulfate was detectable in bone for as
      long as 8 weeks after implantation. Levels as high as 4,746 micrograms/ml were
      present in the wound exudate for the first 7 days. Levels in the serum peaked at
      1.03 micrograms/ml. Urine levels peaked at 135 micrograms/ml.

PMID- 9167629
TI  - Similar effects of recombinant human insulin-like growth factor-I and II on
      cellular activities in flexor tendons of young rabbits: experimental studies in
      vitro.
AB  - To improve the understanding of factors with the potential of affecting the
      healing of flexor tendons, this study compared the cellular effects of
      recombinant human insulin-like growth factor-II with those of recombinant human
      insulin-like growth factor-I in matched pairs of deep flexor tendons of young
      rabbits. Dose-response effects on the synthesis of DNA and matrix proteins of
      either factor alone or in combination were investigated in short-term culture,
      and effects on synthesis and turnover of matrix components were compared in long
      term culture. Both factors stimulated proteoglycan, collagen, noncollagen
      protein, and DNA synthesis in a dose-dependent manner in the range of 10-500
      ng/ml. Insulin-like growth factor-I increased proteoglycan synthesis to as much
      as six times that of controls but was less potent than insulin-like growth factor
      II. Both factors stimulated increased cell proliferation by as much as five times
      compared with control values, but insulin-like growth factor-I was more potent
      than insulin-like growth factor-II. The two factors in combination did not
      enhance the synthesis of matrix proteins and DNA as compared with either factor
      alone. Insulin-like growth factor-I counteracted the decrease in collagen
      synthesis and stimulated protein synthesis to a higher degree than insulin-like
      growth factor-II in long-term culture. Both factors had similar effects on matrix
      turnover, with estimated half times (t1/2) for elimination of newly labeled
      proteoglycans and proteins of 11 and 8 days, respectively. Insulin-like growth
      factor-II is capable of stimulating cell proliferation and matrix metabolism in
      tendon explants of young rabbits at levels similar to those of insulin-like
      growth factor-I; in combination, the two growth factors are unable to augment the
      stimulatory effects of either of the factors alone.

PMID- 9167630
TI  - Contact pressure and tension in anterior cruciate ligament grafts subjected to
      roof impingement during passive extension.
AB  - Contact between an anterior cruciate ligament graft and the intercondylar roof
      has been termed roof impingement. Grafts with impingement sustain permanent
      damage, and if the injury is extensive enough, then the graft may fail, causing
      recurrent instability. This study evaluated two mechanical factors that could be
      responsible for the graft injury associated with roof impingement: an increase in
      graft tension or elevated pressures between the graft and the roof, or both. An
      anterior cruciate ligament reconstruction was performed using an Achilles tendon
      graft in five fresh-frozen cadaveric knees. Using a six-degree-of-freedom load
      application system, the anterior displacement of the knee with the native
      anterior cruciate ligament was restored in the reconstructed knee at a flexion
      angle of 30 degrees and with an anterior force of 200 N applied. Pressure between
      the graft and intercondylar roof, graft tension, and flexion angle were measured
      during passive knee extension for three tibial tunnel placements (anterior,
      center, and posterior). Intercondylar roof impingement increased the contact
      pressure between the graft and the roof but had no significant effect on graft
      tension. Therefore, during passive knee extension, the contact pressure between
      the anterior cruciate ligament graft and the intercondylar roof is a more likely
      cause of graft damage than increased graft tension.

PMID- 9167631
TI  - Migration and healing of ligament cells under inflammatory conditions.
AB  - It is well documented that the adult human medial collateral ligament has a
      functional healing response, whereas the anterior cruciate ligament does not. The
      differential healing responses of the medial collateral and anterior cruciate
      ligaments could be due to factors caused by different biological conditions and
      locations in vivo. In addition, different intrinsic properties of the constituent
      cells of these ligaments may contribute to their different healing abilities.
      Ligament healing follows an orderly process of hemorrhage, inflammation,
      proliferation, and remodeling. At the cellular level, healing involves a cell's
      detachment from and attachment to the matrix adjacent to the wound area,
      migration, and proliferation. This study sought to investigate whether, during
      migration, the responses of the medial collateral and anterior cruciate ligament
      fibroblasts are intrinsically different under the same inflammatory conditions.
      Human medial collateral and anterior cruciate ligament fibroblast cells were
      cultured, and in vitro wounds were simulated by streaking the cells with an
      inoculating loop, creating a cell-free area. The migration of the cells into this
      gap, thus filling the cell-free area, was observed. Two sets of experiments were
      conducted; one varied the wound width and the other added the inflammatory
      factors tumor necrosis factor-alpha, complement C5a, and lipopolysaccharide. As
      the width of the wound increased, the rate of recovery decreased for both types
      of ligament cells (slope: anterior cruciate ligament, 0.13 hour/micron and medial
      collateral ligament, 0.10 hour/micron). Also, the three inflammatory factors used
      all inhibited the recovery rates of both ligaments to ones that were 1.4-2.3
      times slower than controls. However, in both sets of experiments, the anterior
      cruciate ligament fibroblasts were more sensitive to inflammatory factors, and
      the medial collateral ligament fibroblasts had faster recovery rates (anterior
      cruciate ligament, 1.2-3.4 times slower than rates for medial collateral ligament
      fibroblasts, excluding those under lipopolysaccharide treatment). The results
      showed that medial collateral and anterior cruciate ligament fibroblasts
      responded differently under the same inflammatory conditions. This may suggest
      that these differences in intrinsic properties contribute to their different
      healing responses and abilities.

PMID- 9167632
TI  - Evaluation of the effect of joint constraints on the in situ force distribution
      in the anterior cruciate ligament.
AB  - The function of the anterior cruciate ligament was investigated for different
      conditions of kinematic constraint placed on the intact knee using a six-degree
      of-freedom robotic manipulator combined with a universal force-moment sensor. To
      do this, the in situ forces and force distribution within the porcine anterior
      cruciate ligament during anterior tibial loading up to 100 N were compared at 30,
      60, and 90 degrees of flexion under: (a) unconstrained, five-degree-of-freedom
      knee motion, and (b) constrained, one-degree-of-freedom motion (i.e., anterior
      translations only). The robotic/universal force-moment sensor testing system was
      used to both apply the specified external loading to the intact joint and measure
      the resulting kinematics. After tests of the intact knee were completed, all soft
      tissues except the anterior cruciate ligament were removed, and these motions
      were reproduced such that the in situ force and force distribution could be
      determined. No significant differences in the magnitude of in situ forces in the
      anterior cruciate ligament were found between the unconstrained and constrained
      testing conditions. In contrast, the direction of in situ force changed
      significantly; the force vector in the unconstrained case was more parallel with
      the direction of the applied tibial load. In addition, the distribution of in
      situ force between the anteromedial and posterolateral bundles of the ligament
      was nearly equal for all flexion angles for the unconstrained case, whereas the
      anteromedial bundle carried higher forces than the posterolateral bundle at both
      60 and 90 degrees of flexion for the constrained case. This demonstrates that the
      constraint conditions placed on the joint have a significant effect on the
      apparent role of the anterior cruciate ligament. Specifically, constraining joint
      motion to one degree of freedom significantly alters both the direction and
      distribution of the in situ force in the ligament from that observed for
      unconstrained joint motion (five degrees of freedom). Furthermore, the changes
      observed in the distribution of force between the anteromedial and posterolateral
      bundles for different constraint conditions may help elucidate mechanisms of
      injury by providing new insight into the response of the anterior cruciate
      ligament to different types of external knee loading.

PMID- 9167633
TI  - In situ forces in the anterior cruciate ligament and its bundles in response to
      anterior tibial loads.
AB  - The anterior cruciate ligament has a complex fiber anatomy and is not considered
      to be a uniform structure. Current anterior cruciate ligament reconstructions
      succeed in stabilizing the knee, but they neither fully restore normal knee
      kinematics nor reproduce normal ligament function. To improve the outcome of the
      reconstruction, it may be necessary to reproduce the complex function of the
      intact anterior cruciate ligament in the replacement graft. We examined the in
      situ forces in nine human anterior cruciate ligaments as well as the force
      distribution between the anteromedial and posterolateral bundles of the ligament
      in response to applied anterior tibial loads ranging from 22 to 110 N at knee
      flexion angles of 0-90 degrees. The analysis was performed using a robotic
      manipulator in conjunction with a universal force-moment sensor. The in situ
      forces were determined with no device attached to the ligament, while the knee
      was permitted to move freely in response to the applied loads. We found that the
      in situ forces in the anterior cruciate ligament ranged from 12.8 +/- 7.3 N under
      22 N of anterior tibial load applied at 90 degrees of knee flexion to 110.6 +/-
      14.8 N under 110 N of applied load at 15 degrees of flexion. The magnitude of the
      in situ force in the posterolateral bundle was larger than that in the
      anteromedial bundle at knee flexion angles between 0 and 45 degrees, reaching a
      maximum of 75.2 +/- 18.3 N at 15 degrees of knee flexion under an anterior tibial
      load of 110 N. The magnitude of the in situ force in the posterolateral bundle
      was significantly affected by knee flexion angle and anterior tibial load in a
      fashion remarkably similar to that seen in the anterior cruciate ligament. The
      magnitude of the in situ force in the anteromedial bundle, in contrast, remained
      relatively constant, not changing with flexion angle. Significant differences in
      the direction of the in situ force between the anteromedial bundle and the
      posterolateral bundle were found only at flexion angles of 0 and 60 degrees and
      only under applied anterior tibial loads greater than 66 N. We have demonstrated
      the nonuniformity of the anterior cruciate ligament under unconstrained anterior
      tibial loads. Our data further suggest that in order for the anterior cruciate
      ligament replacement graft to reproduce the in situ forces of the normal anterior
      cruciate ligament, reconstruction techniques should take into account the role of
      the posterolateral bundle in addition to that of the anteromedial bundle.

PMID- 9167634
TI  - Effect of freeze-drying or gamma-irradiation on remodeling of tendon allograft in
      a rat model.
AB  - Freezing or freeze-drying and gamma-irradiation are techniques currently used for
      processing tendon allografts. However, it is still unknown how these processing
      methods affect graft remodeling. In this study, we used a rat patellar tendon
      transplantation model to investigate the effect of various processing methods on
      remodeling by quantifying loss of collagen labeled with a radioactive isotope.
      The grafts were divided into the following four groups according to the
      processing method: fresh-frozen, freeze-dried, fresh-frozen and gamma-irradiated,
      or freeze-dried and gamma-irradiated. The percentage of donor collagen,
      calculated from hydroxyproline content and radioactivity level, was used as an
      indicator of graft remodeling. At 2 weeks, the level of donor collagen in the
      fresh-frozen group was 62%; in the freeze-dried group, 59%; in the fresh-frozen
      and irradiated group, 57%; and in the freeze-dried and irradiated group, 44%. At
      4 weeks, the percentage of donor collagen remaining in grafts decreased to 38% in
      the fresh-frozen group, 19% in the freeze-dried group, 27% in the fresh-frozen
      and irradiated group, and 12% in the freeze-dried and irradiated group. Finally,
      at 12 weeks, the levels were 19% in the fresh-frozen group, 20% in the freeze
      dried group, 15% in the fresh-frozen and irradiated group, and 6% in the freeze
      dried and irradiated group. The percentages of donor collagen in the freeze-dried
      and the fresh-frozen and irradiated groups were significantly lower than that in
      the fresh-frozen group at 4 weeks. The values for the freeze-dried and irradiated
      group were significantly lower than those for the fresh-frozen and irradiated
      group at 4 and 12 weeks. These data suggest that freeze-drying, freeze-drying
      followed by gamma-irradiation, and fresh-freezing followed by gamma-irradiation
      temporarily accelerate graft remodeling.

PMID- 9167635
TI  - Osteoclast formation during tumor osteolysis does not require proliferating
      osteoclast precursor cells.
AB  - The cellular mechanism or mechanisms through which tumors induce osteoclast
      formation at sites of tumor osteolysis is unknown. To test the hypothesis that
      osteoclast formation at sites of tumor osteolysis reflects influences that tumors
      have on proliferating osteoclast precursor cells, a novel in vivo experimental
      model was developed that produced mice that were deficient in osteoclasts (op/op)
      and were depleted (by way of total body irradiation) of proliferating osteoclast
      precursor cells. The femora of irradiated op/op mice were injected with tumor
      cells (2472 clone) that had been previously shown to form osteolytic tumors and
      to induce focal osteoclastogenesis, and the influence of these tumor cells on
      osteoclast formation was determined in op/op mice that were depleted of
      proliferating osteoclast precursor cells. The results indicated that 2472 tumor
      cells induced osteoclast formation in op/op mice despite the absence of
      proliferating osteoclast precursor cells. This finding disproved the hypothesis
      under investigation and suggests that osteoclast formation at sites of tumor
      osteolysis reflects influences of tumors on postmitotic, not proliferating,
      osteoclast precursor cells.

PMID- 9167636
TI  - Stimulation of bone formation by intraosseous application of recombinant basic
      fibroblast growth factor in normal and ovariectomized rabbits.
AB  - The effect on intraosseous bone formation of a single local injection of
      recombinant human basic fibroblast growth factor into the distal femur was
      examined in normal and ovariectomized rabbits. In normal rabbits, basic
      fibroblast growth factor increased bone mineral density around the injected site
      in a dose-dependent manner at 4 weeks, with significant effects at concentrations
      of 400 micrograms and greater. Doses of 400 and 1,600 micrograms of basic
      fibroblast growth factor increased bone mineral density by 8 and 9%,
      respectively, compared with the opposite control femur. Histological examination
      showed that basic fibroblast growth factor (400 micrograms) induced the
      proliferation or recruitment of undifferentiated mesenchymal cells around the
      existing trabeculae at 3 days after the injection. For the first 2 weeks, osteoid
      formation was strongly stimulated, and this was followed by mineral apposition
      for another 2 weeks, at which time the femurs were harvested. Consequently, basic
      fibroblast growth factor stimulated intraosseous bone formation at 4 weeks. We
      speculate that the direct action of basic fibroblast growth factor on bone
      formation may be to stimulate proliferation or recruitment of minimally
      differentiated mesenchymal cells and to initiate the cascade of events in later
      stages of bone formation. In ovariectomized rabbits, basic fibroblast growth
      factor (400 micrograms) also increased bone mineral density, histomorphometrical
      bone formation markers, and trabecular connectivity to levels similar to those in
      rabbits who had received sham operations.

PMID- 9167637
TI  - Method to impact in vivo rabbit femoral cartilage with blows of quantifiable
      stress.
AB  - The purpose of this study was to develop a technique by which a known stress
      could be applied uniformly across the femoral cartilage of a rabbit as a model
      for the development of post-traumatic arthritis. A system to impact the cartilage
      was designed that consisted of an apparatus to deliver a blow of quantifiable
      force, a method to apply the stress uniformly over the impact area, and a way to
      accurately measure the impact area. The knee joints of cadaveric New Zealand
      White rabbits were surgically exposed with the knee flexed so that the distal
      femoral articular surface was perpendicular to an impactor. With the knee fixed
      in position, a cup containing polymethylmethacrylate bone cement was applied to
      create an exact contour of the femoral surface, and the cement was allowed to
      cure. The form was then rested on the rabbit knee, and a drop tower released a
      weight of known mass from a known height onto an impactor (instrumented with
      strain gauges to measure the compressive force) that was attached to the cup. The
      area of the impacted surface was determined and, with the measured force, was
      used to calculate an accurate estimate of the impact stress. This method can be
      performed under sterile conditions, and therefore it is well suited for survival
      experiments in which the long-term effects of impact to cartilage will be
      studied.

PMID- 9167638
TI  - Alterations in the mechanical behavior of the human lumbar nucleus pulposus with
      degeneration and aging.
AB  - This study tested the hypothesis that changes in the morphology and composition
      of the nucleus pulposus with age and degeneration have associated changes in its
      mechanical properties. A torsional shear experiment was used to determine
      viscoelastic shear properties of cylindrical samples of human nucleus pulposus
      with large ranges of grades of morphological degeneration (normal to severely
      degenerated) and ages (range: 16-88 years; average: 57 +/- 21.5 years).
      Viscoelastic shear properties were determined from stress-relaxation and dynamic
      sinusoidal tests. A linear viscoelastic law with a variable-amplitude relaxation
      spectrum was used to model experimental behaviors of nucleus pulposus specimens.
      A statistically significant increase in the instantaneous and dynamic shear
      moduli was found with increasing age and grade of degeneration; the values for
      moduli ranged from 5.0 to 60 kPa. A significant decrease in tan delta was also
      detected; the values ranged from 0.43 to 0.33, indicating a decreased capacity
      for the nucleus pulposus to dissipate energy. The dynamic modulus and tan delta
      were also significantly affected by frequency. It was generally concluded that
      the nucleus pulposus undergoes a transition from "fluid-like" behavior to more
      "solid-like" behavior with aging and degeneration.

PMID- 9167639
TI  - Resistance and conduit arteries following converting enzyme inhibition in
      hypertension.
AB  - Alterations in the structure of resistance and conduit arteries are a
      characteristic hallmark in hypertension. Studies carried out in hypertensive rats
      and in humans suggest that angiotensin I-converting enzyme inhibition has an
      effect on arterial structure of resistance arteries. In hypertensive rats the
      reduction of the media to lumen ratio is dose-dependent and significantly
      different from the effects of other antihypertensive agents at doses causing an
      equal degree of blood pressure reduction. In large conduit arteries, hypertrophy
      of the vessels is reversed by converting enzyme inhibition both in hypertensive
      rats (studies on central arteries) and in human (studies on peripheral arteries)
      hypertension. The reduction of hypertrophy is associated with a decrease in
      arterial stiffness, partly independent of blood pressure reduction. These
      findings suggest that regression of structural vascular changes may contribute to
      both the decrease in the arteriolar resistance and the improvement in the
      buffering function of large arteries. The decrease in arteriolar resistance and
      the improvement of large artery compliance may participate in blood pressure
      reduction and an improvement in pulse pressure amplification produced by
      converting enzyme inhibition.

PMID- 9167640
TI  - G proteins and phospholipase C mediate thrombin-induced generation of plasminogen
      activator inhibitor-1 from vascular smooth muscle cells.
AB  - The present study investigated transcellular signalling mechanism involved in
      thrombin-induced production of plasminogen activator inhibitor-1 (PAI-1) in
      cultured vascular baboon aortic smooth muscle cells (BASMC). Treatments with
      thrombin dose-dependently increased the steady state levels of PAI-1 mRNA and the
      generation of PAI-1 antigen from BASMC. Thrombin receptor-activating peptide
      mimicked the effect of thrombin on the generation of PAI-1. Sodium fluoride (1
      mM) stimulated PAI-1 generation from BASMC. Pertussis toxin dose-dependently
      suppressed thrombin-induced increase of PAI-1 generation. Treatment with 5 mM
      neomycin, 10 microM U73122 or 1 microM calphostin C blocked thrombin-induced PAI
      1 generation. Phorbol myristate acetate at 10 nM for 3 h strongly stimulated the
      generation of PAI-1 from BASMC. Forskolin (100 microM) or 8-bromo-cAMP (100
      microM) suppressed thrombin-induced PAI-1 generation. The responses of quiescent
      BASMC to thrombin or the inhibitors on PAI-1 generation were comparable to that
      of growing cells. The results of the present study suggest that pertussis toxin
      sensitive G proteins and a phospholipase C are involved in thrombin-induced
      generation of PAI-1 in BASMC, which may transmit signals from occupied thrombin
      receptor to protein kinase C and thereby increase the generation of PAI-1.
      Elevated levels of intracellular cAMP may negatively regulate the generation of
      PAI-1 from vascular SMC.

PMID- 9167641
TI  - Adrenoceptor-mediated regulation of the contractility in horse penile resistance
      arteries.
AB  - The receptors mediating the contractions to both exogenously applied
      noradrenaline and electrical field stimulation (EFS) were characterized in horse
      isolated penile resistance arteries. The alpha 1-adrenoceptor-selective
      antagonist, prazosin, caused competitive rightward shifts of the contractile
      concentration-response curves (CRC) to phenylephrine. The alpha 2-antagonist,
      rauwolscine, also displaced to the right the CRC to the alpha 2-adrenoceptor
      selective agonist, BHT 920. EFS (0.3 ms, 20-second trains) caused tetrodotoxin
      sensitive frequency-dependent contractions which were enhanced in the presence of
      NG-nitro-L-arginine (L-NOARG, 3 x 10(-5) M), but not affected by mechanical
      endothelial cell removal. In experiments performed in the presence of L-NOARG,
      prazosin inhibited contractions to EFS, while rauwolscine inconsistently enhanced
      the contractile responses. Exogenously added noradrenaline induced contractions
      which were not changed in endothelium-denuded arteries, but significantly
      increased in the presence of L-NOARG. Prazosin inhibited the noradrenaline
      induced contractions, while rauwolscine did not change the response to
      noradrenaline either alone or in the presence of prazosin. In the presence of
      phentolamine (10(-5) M), isoprenaline, adrenaline and the beta 2-adrenoceptor
      agonist, salbutamol, concentration-dependently relaxed penile resistance
      arteries, while the relaxations to noradrenaline and dobutamine, which activate
      beta 1-adrenoceptors, were negligible. Isoprenaline-induced relaxations were not
      changed in the presence of the beta 1-antagonist, atenolol (10(-7)-10(-6) M), but
      competitively inhibited by the beta 2-adrenoceptor antagonist, butoxamine (10(-6)
      10(-5) M). The present results indicate that stimulation of adrenergic nerves in
      horse penile resistance arteries releases noradrenaline, which induces
      vasoconstriction through a predominant activation of alpha 1-adrenoceptors, while
      postjunctional alpha 2-adrenoceptors apparently play a minor role. Functional
      beta 2-adrenoceptors are also present in these arteries.

PMID- 9167642
TI  - Inhibition of calcium entry preserves contractility of arterial smooth muscle in
      culture.
AB  - The addition of the growth stimulator fetal calf serum (FCS, 10%) to rings of rat
      tail artery causes an increase in [Ca2+]i, accompanied by contraction. This
      response was inhibited by the calcium entry blocker verapamil (1 microM). To
      investigate the effect of Ca2+ entry blockade on growth and contractility, rings
      of rat tail artery were cultured for 4 days in medium with or without FCS and
      then mounted for tension registration and stimulated with noradrenaline (NA) or
      high-K+ solution. In cultured rings growth was quantitated by [3H]-thymidine
      incorporation and increase in protein contents. FCS in the medium stimulated DNA
      synthesis by about 2-fold and increased protein contents by about 70%. The growth
      stimulated cultured rings developed less force than freshly prepared rings (2.2
      +/- 0.3 vs. 8.3 +/- 1.0 mN/mm). The addition of 1 microM verapamil to the medium
      during culture increased maximal NA-evoked force to 5.0 +/- 0.4 mN/mm but had no
      effect on the increases in DNA synthesis and protein contents. Force developed by
      growth-arrested rings, cultured in the absence of FCS, was not different from
      that of freshly prepared rings (7.2 +/- 0.6 mM/mm). Verapamil did not affect
      maximal force in these rings. Similar responses were seen when contraction was
      elicited by high-K+ solution. We conclude that verapamil, present during culture,
      preserves contractility of arterial smooth muscle, and that this effect is not
      parallel to inhibition of growth.

PMID- 9167643
TI  - Myogenic tone in coronary arteries from spontaneously hypertensive rats.
AB  - The aims of this study were to investigate myogenic tone in cannulated coronary
      arteries from SHR (spontaneously hypertensive rats) and WKY (Wistar-Kyoto rats)
      at 5 and 20 weeks of age under pressurised no-flow conditions. Pressure-diameter
      relationships (20-200 mm Hg) were determined in the presence (active) and absence
      (passive) of calcium and myogenic tone at each pressure was calculated. Active,
      but not passive diameter-pressure relationships were significantly different
      between strains at both ages. Active diameters were similar between strains at
      pressures up to 140 mm Hg at 5 and 20 weeks. At higher pressures SHR arteries
      generated more tone. Maximum myogenic tone was similar between strains in spite
      of increased wall thickness in the SHR at both ages. Endothelium denudation
      increased myogenic tone to a greater extent in the SHR at both ages. Active
      diameters of endothelium-denuded SHR arteries were smaller than those of WKY in
      the range 20-120 mm Hg at 5 week and 20-80 and 160-180 mm Hg at 20 weeks. These
      results demonstrate that during both the developmental and established phases of
      hypertension, myogenic tone is not enhanced in intact SHR coronary arteries,
      except at the highest pressures. Following endothelium removal SHR arteries
      generated greater myogenic tone also at lower pressures. These data demonstrate a
      greater endothelium-mediated antagonism of myogenic tone in SHR coronary
      arteries.

PMID- 9167644
TI  - Effect of pressurization on mechanical properties of mesenteric small arteries
      from spontaneously hypertensive rats.
AB  - The mechanical properties of the wall of isolated perfused arterial segments of
      mesenteric small arteries from 17-week-old spontaneously hypertensive rats (SHR)
      and age-matched Wistar Kyoto rats (WKY) were investigated. Third-order branches
      of mesenteric arteries were mounted in a pressure myograph chamber and
      pressurized from 1 to 140 mm Hg. Under isobaric conditions, the outer diameter
      and the lumen of small arteries studied were smaller in SHR than in WKY, whereas
      media width, media cross-sectional area and media-lumen ratio were greater in
      SHR. Under passive conditions, the total change in internal and external diameter
      in response to increasing intravascular pressure was smaller in arteries from
      SHR. Incremental distensibility was significantly lower in arteries of SHR at
      intravascular pressures between 1 and 40 mm Hg, but was significantly greater
      between pressures of 40-100 mm Hg. Wall stress generated by intravascular
      pressure was significantly smaller in arteries from SHR. As a function of wall
      strain (under isometric conditions), stress and incremental elastic modulus were
      shifted to the left in SHR vessels. Under isobaric conditions or in relation to
      wall stress, the slope of elastic modulus was smaller in SHR. This decrease in
      elastic modulus may confer additional elasticity to the vascular wall of
      resistance arteries from SHR. The presence of a greater distensibility at
      physiological levels of intravascular pressure and decreased incremental elastic
      modulus indicates that the changes in the structure of small mesenteric arteries
      in SHR can be defined as the result of a combination of eutrophic and
      hypertrophic remodeling.

PMID- 9167645
TI  - Aortic elastin and collagen content and synthesis in two strains of rats with
      different susceptibilities to rupture of the internal elastic lamina.
AB  - We have previously characterized two normotensive strains of rats which differ
      markedly in their susceptibility to spontaneous rupture of the internal elastic
      lamina (IEL), the Brown Norway (BN) being very susceptible and the Long Evans
      (LE) being resistant. Here we quantified biochemically the elastin and collagen
      content of aortae from adult male BN and LE rats aged 12, 18 and 22 weeks and
      showed that the elastin content was lower and the collagen content higher in the
      BN strain than in the LE strain, resulting in a markedly lower elastin/collagen
      ratio in the former strain. These modifications were present both in the thoracic
      aorta, which is devoid of IEL ruptures, and in the abdominal segment where
      ruptures frequently occur in the BN rat, suggesting that they could represent a
      predisposing factor in the presence of other local factors. Quantifications of
      relevant mRNAs in aortae of younger male BN and LE rats by Northern blot showed
      that there are lower tropoelastin transcript levels in the BN rat at 6 weeks in
      both thoracic and abdominal segments than in the age-matched LE rat. In contrast
      there was no consistent interstrain difference in alpha 1 type I collagen
      transcripts and alpha 1 type III collagen transcripts were higher in the BN aorta
      only at 6 weeks in the abdominal segment. We conclude that the BN rat presents an
      aortic elastin deficit which appears to be in part explained by a decreased
      elastin synthesis in young, growing rats and may be genetically determined.
      However, a direct relation of this elastin deficit with susceptibility to rupture
      of the IEL cannot be concluded from this study.

PMID- 9167646
TI  - Age-related differences in elastic properties of the upper arm vascular bed in
      healthy adults.
AB  - The significance of age-related changes in arterial stiffness has remained
      largely uncertain in healthy subjects. This appears to be partly due to
      difficulties in the interpretation of methods for measuring arterial stiffness in
      vivo. Therefore, a recently developed electrical bioimpedance method was used for
      studying elastic properties of a vascular bed as a function of age. In 66 healthy
      subjects, aged 22-82 years, we investigated the vascular bed of an upper arm
      segment. This vascular bed showed an age-related decrease in the venous blood
      volume (r = -0.31, p < 0.01) and in the distensibility, the inverse of stiffness,
      of the larger arteries (r = -0.38, p < 0.001). The distensibility of the arterial
      bed as a whole at normotensive blood pressure, however, appeared to increase with
      age (r = 0.32, p < 0.005). The arterial and venous blood volumes, arterial
      compliance and extravascular fluid volume were significantly higher in the males
      than in the females. Practically all investigated vascular properties appeared to
      be related with height, body mass or body mass index. We concluded that
      comparative studies concerning vascular properties should preferably be performed
      in subjects matched as to age, gender, height and body mass. In healthy subjects
      the smaller arteries adjust to the age-related decrease in large artery
      distensibility by means of an age-related increase in distensibility. These age
      related changes in arterial distensibility are caused by changes in the females,
      and seem to be associated with age-related changes in body mass index rather than
      with aging per se.

PMID- 9167647
TI  - Hyponatremia and hypernatremia.
AB  - Hyponatremia and hypernatremia are common electrolyte disorders resulting from
      disorders in water homeostasis. Hyponatremia usually results from defects in free
      water excretion, although increased intake may also contribute. The treatment of
      hyponatremia has been controversial because of the high associated morbidity and
      mortality and the observation that rapid correction of hyponatremia is associated
      with the development of central pontine myelinolysis. Mild hyponatremia should be
      treated with water restriction alone, whereas severe acute or symptomatic
      hyponatremia should initially be corrected rapidly until symptoms resolve
      followed by more gradual correction. In all cases, treatment should be
      individualized on the basis of severity, cause, and duration of the hyponatremia.
      Hypernatremia results from impaired water ingestion, although increased water
      losses are often contributory. Hospital-acquired hypernatremia is usually
      iatrogenic because of inadequate water prescription and is therefore preventable.
      Hypernatremia is also associated with high morbidity and mortality, both as a
      result of the underlying disease and inadequate treatment. The primary treatment
      of hypernatremia is water replacement-repleting water deficits and replacing
      ongoing losses. Additional treatment should be directed at eliminating excess
      water losses.

PMID- 9167648
TI  - Hypokalemia and hyperkalemia.
AB  - This article discusses the causes and nature of hypokalemia and hyperkalemia.
      Diagnosis, testing, drug administration, and general management are outlined in
      detail.

PMID- 9167649
TI  - Asymptomatic urinary abnormalities. Hematuria and proteinuria.
AB  - Asymptomatic urinary abnormalities including hematuria and proteinuria are
      commonly detected in routine urinalysis. They may be of benign etiology or
      indicative of more serious underlying disease. This article is intended to give
      clinicians a guide for evaluation of hematuria and proteinuria.

PMID- 9167650
TI  - Diagnosis and management of glomerular diseases.
AB  - Glomerular diseases are a diagnostic challenge. Early recognition and timely
      institution of appropriate treatment are critical to optimum outcome in many
      patients, especially those with rapidly progressive glomerulonephritis. The
      clinical presentations and laboratory data provide adequate presumptive diagnoses
      in some patients; however, renal biopsy evaluation is often required for a
      definitive diagnosis.

PMID- 9167651
TI  - Diabetic nephropathy.
AB  - Diabetic nephropathy accounts for almost a third of all causes of ESRD.
      Microalbuminuria screening among diabetics can offer early detection of incipient
      nephropathy. Aggressive treatment with ACE inhibitors may delay the onset of
      overt renal failure or delay its progression. Furthermore, intensive control of
      blood glucose has also been proven to prevent the microvascular complications of
      diabetes and should be pursued in both IDDM and NIDDM. The high association of
      diabetes mellitus with hypertension presents another problem to the clinician. It
      is necessary to control blood pressure to prevent further progression of renal
      failure. The choice of antihypertensive medications, however, becomes a
      therapeutic dilemma because of the metabolic and lipid disturbances that some
      drugs can cause. ACE inhibitors, CCBs, alpha-agonists, and low-dose diuretics,
      alone or in combination, may be tried to normalize blood pressures. Although beta
      blockers are widely used and effective in nondiabetics, these agents should be
      considered the drugs of last resort because of their adverse effects, which are
      particularly troublesome for diabetics. Moderate protein restriction should also
      be advocated as a helpful adjunct to therapy.

PMID- 9167652
TI  - Edema and principles of diuretic use.
AB  - Diuretics have changed the approach to many disease and have turned once fatal
      conditions into tolerable ones. Treatment of salt and water overload and edema
      can be quite satisfying for the clinician as long as the patient is closely
      watched for side effects. Thiazide diuretics have their greatest use in
      hypertension, loop diuretics in edema and congestive heart failure, CA inhibitors
      in glaucoma and altitude sickness, potassium-sparing diuretics in hypokalemia
      induced by other diuretics and ascites, and osmotic diuretics in acute renal
      failure and dialysis. They are among the most widely prescribed medications in
      the world today and rightly have a prominent place in the armamentarium against
      disease.

PMID- 9167653
TI  - Drug-induced nephrotoxicity.
AB  - Drug-induced renal dysfunction is not an uncommon event, which can cause
      significant morbidity and can be easily overlooked. Many medications can lead to
      renal dysfunction through various mechanisms. The most common medications or
      classes of medications along with their clinical presentations are discussed in
      this article. As can be noted, many drugs can cause nephropathy in more than one
      way. Because it is difficult to discuss nephrotoxicities of every reported
      medication, Tables 1, 2, and 3 are provided; although these tables are by no
      means comprehensive, they may serve as further reference. This article is
      intended to provide a broad overview of the spectrum of presentation associated
      with drug-induced nephrotoxicity to guide the clinician to familiarity with this
      entity.

PMID- 9167654
TI  - Urinary tract infections.
AB  - Urinary tract infections (UTIs) are still the precipitating cause for 7 million
      patient visits per year with total costs exceeding one billion dollars.
      Diagnostic modalities have become more "friendly" for the smaller laboratory with
      "dip stick" culture tests providing a rapid method of isolation of pathogens. In
      many cases, empiric therapy is more cost effective than culture in uncomplicated
      UTIs in women. The etiologic organisms implicated in UTIs have not changed
      dramatically over the past two decades, with E. coli still accounting for the
      majority of cases. Antibiotic susceptibility patterns have changed dramatically,
      with ampicillin losing utility die to the emergence of resistance. Quinolones,
      which have been exceedingly active against gram-negative enteric pathogens, are
      no longer universally active and more pathogenic organisms, such as pseudomonas,
      may be resistant. The emergence of other highly resistant organisms, such as
      Enterococcus faecium, must be watched for.

PMID- 9167655
TI  - A practical approach to acute renal failure.
AB  - Acute renal failure represents a wide variety of renal diseases, which may be
      challenging to diagnose and even more challenging to treat. As understanding of
      these diseases improves, so perhaps will clinicians' ability to treat them.

PMID- 9167656
TI  - Nondialysis management of chronic renal failure.
AB  - Chronic renal failure is a complex syndrome encompassing clinical manifestations
      from all the organs in the body. The aims of conservative management are to
      prevent and treat the important clinical manifestations and to prevent the
      progression of renal failure.

PMID- 9167657
TI  - Primary care of patients with renal transplants.
AB  - The number of renal transplant recipients in the community continues to rise due
      to improved organ and patient survival. With increasing emphasis on primary care,
      more organ transplant recipients are being cared for by primary care physicians.
      This article outlines the management of renal transplant recipients and reviews
      the problems unique to this group of patients.

PMID- 9167658
TI  - Medical management of nephrolithiasis.
AB  - About 1 out of 14 males and 1 out of 30 females are afflicted with kidney stones.
      In many of these patients, the disease is recurrent. Fortunately, our
      understanding of the disease and ability to treat renal stone disease has
      increased in the last decade. Parenteral NSAIDs have been shown to be as
      effective as narcotics in treating renal colic. Dietary and drug therapy after
      proper metabolic evaluation of patients with recurrent stones is beneficial in
      reducing the recurrence rate. New understanding of the role of diet and many
      organic inhibitors of crystallization in urine will further broaden the scope of
      management of this common disease.

PMID- 9167659
TI  - Prostate cancer screening and management.
AB  - Several other newer therapeutic modalities are being investigated to determine
      their potential role in the treatment of prostate cancer. Cryotherapy, microwave
      hyperthermia, laser therapy, and high-intensity focused ultrasound have all been
      introduced in recent years. Each of these techniques is based on a different
      principle, yet they all attempt to kill prostate cancer cells in a minimally
      invasive manner. Insufficient follow-up data are available to allow strong
      recommendations regarding these treatments.

PMID- 9167660
TI  - Current classification of fractures. Rationale and utility.
AB  - Fracture classification systems are used on a daily basis in any busy orthopedic
      clinic. They are an essential means by which physicians communicate, make
      treatment decisions, estimate prognosis, and report and compare results. Until
      recently, these classifications have been designed, accepted, and utilized
      without formal critique. By studying and understanding the shortcomings of
      previous systems, we can use this knowledge to construct better ones. Ideally, a
      fracture classification, like any classification, should be reliable,
      reproducible, all inclusive, mutually exclusive, logical, and clinically useful.
      The AO/ASIF classification of long bone fractures provides a unified scheme of
      classification for fractures of the entire skeleton. Despite addressing many of
      the faults of previous classifications, the observer agreement for this system
      drops to unacceptable levels at the group and subgroup levels. Further study is
      warranted to determine how this agreement can be improved.

PMID- 9167661
TI  - Cervical spine trauma. What is new?
AB  - To a large extent, what is new in cervical spine trauma relates to evolving
      indications for the use of various imaging modalities and expanded understanding
      of conditions that may influence traumatic sequelae. The American College of
      Radiology Appropriateness Criteria now provide guidelines for decisions
      concerning imaging in various clinical situations. This article reviews many of
      the publications of the past 6 to 7 years that may contribute to a radiologist's
      understanding of cervical spine injuries.

PMID- 9167662
TI  - Thoracic and lumbar spine trauma.
AB  - The thoracic and lumbar regions of the spine have unique anatomic and
      biomechanical features that result in different characteristic patterns of
      injury. This article reviews common injuries to the thoracic and lumbar spine and
      emphasizes the relationship between anatomic features and characteristic patterns
      of injury. An approach to imaging of the trauma patient is presented, focusing on
      detection and classification of spinal injuries.

PMID- 9167663
TI  - Pelvic and acetabular trauma.
AB  - Blunt pelvic trauma may lead to disruption of the pelvic ring, acetabular
      fracture, and significant soft tissue injury. The radiologist must be familiar
      with not only the imaging approach to these lesions but also the anatomy,
      biomechanics of injury, and fracture classification to communicate effectively
      with trauma surgeons and to participate as a member of the trauma team.

PMID- 9167664
TI  - Role of MR imaging in acute injuries to the appendicular skeleton.
AB  - Clinical applications of MR imaging in the setting of acute extremity injuries
      are discussed in general and by anatomic regions. General indications include
      physeal injuries, occult fractures, stress fractures, musculotendinous injuries,
      and ligamentous injuries. Indications of MR imaging in the acute injury setting
      have been expanding. MR imaging is often used to triage patients definitively to
      surgical versus conservative treatment for such conditions as suspected hip
      fracture. High-performance athletes are also often imaged acutely. Radiologists
      need to be familiar with the possible applications of MR imaging to acute
      extremity injuries, and discuss with referring physicians what indications are
      appropriate locally. In this way, the role of MR imaging in this area will be
      further defined in the future.

PMID- 9167665
TI  - MR imaging of acute orthopedic trauma to the extremities.
AB  - This article outlines the imaging role of MR imaging in evaluating acute
      orthopedic trauma to the extremities. MR imaging is compared, where possible,
      with CT scan, scintigraphy, and ultrasound. The article specifically explores the
      role of MR imaging in evaluating soft tissue injury accompanying fracture,
      emphasizes an established role in occult fracture detection, reviews the role of
      MR imaging in evaluating neurovascular integrity following fracture, and
      underscores the utility of MR imaging in evaluating trauma to the growth plate.

PMID- 9167666
TI  - Imaging of skeletal and soft tissue injuries in and around the knee.
AB  - This article addresses the place of MR imaging in the diagnosis of knee injuries.
      MR imaging of subtle fractures and bone contusions is described with emphasis
      placed on those types of fractures frequently associated with specific patterns
      of soft tissue injury. Soft tissue injuries are divided into ligamentous,
      meniscal, and muscular; each is discussed separately. The MR imaging appearance
      of these lesions is explained.

PMID- 9167667
TI  - Challenging fractures of the foot and ankle.
AB  - The foot and ankle is one of the most imaged parts of the body. Although most
      plain radiographs reveal no bony injury, subtle fractures can be overlooked.
      Because it is important to detect these fractures at the time of injury, a review
      of the most commonly missed foot and ankle fractures is presented.

PMID- 9167668
TI  - MR imaging of injuries to the small joints.
AB  - This article describes MR imaging of acute and chronic injuries of the ankle and
      foot, elbow, and hand and wrist. Conditions discussed include ligament and tendon
      injuries, fractures and bone bruises, osteochondral defects, foreign bodies, and
      posttraumatic ganglions. Other topics covered include fasciitis, nerve and muscle
      injuries about the elbow, and triangular fibrocartilage tears.

PMID- 9167670
TI  - Skeletal injuries in the pediatric patient.
AB  - Immature skeleton is different from adult skeleton with unique vulnerability to
      acute and chronic injuries at the growth plate. Recognition and differential
      diagnosis of inflicted skeletal injury are important. Familiarity with the
      dynamic changes of growing skeleton in normal children is key to the recognition
      of pathologic states.

PMID- 9167669
TI  - Imaging of acute injuries to the wrist and hand.
AB  - This article reviews the basic characteristics of common fractures and
      dislocations in the hand and wrist. There is increasing recognition that
      fractures and dislocations of the hand and wrist can result in long-term pain and
      dysfunction. This article includes descriptions and, when helpful,
      classifications for these fractures with attention to those features that are of
      prognostic and therapeutic significance. With prompt recognition and proper
      characterization of these injuries, patients can be triaged to the orthopedic
      surgeon for early and more aggressive treatment.

PMID- 9167671
TI  - Acute and chronic avulsive injuries.
AB  - Avulsive injuries are common traumatic lesions, especially in young athletes.
      They can be acute, resulting from excessive tensile forces, or chronic, due to
      overuse. Avulsion injuries can resemble osteomyelitis or neoplasm and, therefore,
      familiarity with the radiographic patterns as well as the different muscle
      attachments is helpful for the clinician to arrive at the correct diagnosis. This
      article discusses acute and chronic avulsive injuries in the pelvis, knee, elbow,
      shoulder, and foot.

PMID- 9167672
TI  - Complications of skeletal trauma.
AB  - Complications of skeletal trauma include a wide variety of problems. Vascular
      complications are of prime importance in the early phase of the trauma. Most
      skeletal problems, including problems in fracture healing, osteomyelitis, and
      osteonecrosis, become clinically important in the later stages. It is hoped that
      radiologists' attention to such problems may make early detection possible and
      may improve the functional outcome in such patients.

PMID- 9167673
TI  - Criteria for reporting fine needle aspiration on palpable and nonpalpable masses
      of the breast.

PMID- 9167675
TI  - Cytologic features of fibromatosis colli of infancy.
AB  - OBJECTIVE: To present the characteristic cytologic features of fibromatosis colli
      in infancy. STUDY DESIGN: A series of 14 children with the typical clinical
      presentation of fibromatosis colli of infancy on whom fine needle aspiration had
      been performed. RESULTS: The cytologic features were identical in all cases. All
      samples contained degenerated muscle cells in varying numbers, including
      multinucleated cells with abundant cytoplasm. Fibroblasts appeared mainly as
      single cells but with admixed clusters of varying sizes. The cells were slender,
      spindle shaped or somewhat rounded, with benign nuclear characteristics.
      CONCLUSION: In the typical clinical setting and with the cytologic findings
      above, surgical biopsy of the lesion may be avoided.

PMID- 9167674
TI  - Brush cytology and biopsy in the diagnosis of colorectal cancer. A comparison.
AB  - OBJECTIVE: To determine the usefulness of brush cytology of colorectal lesions as
      compared to biopsy examination. STUDY DESIGN: One hundred brushing cytologies and
      biopsies were performed on patients who underwent colonoscopic examination for
      different symptoms. The cytologic smears were classified into five cytologic
      diagnostic categories. The histologic diagnoses were adenocarcinoma, adenoma and
      nonneoplastic lesion. RESULTS: Twenty-six cases were cytologically positive for
      malignant cells, and all were histologically diagnosed as adenocarcinoma.
      Nineteen cases were suspicious for malignancy on cytology; histologically, eight
      of them showed adenocarcinoma. Two other cases proved to be adenocarcinoma in
      subsequent biopsies. Nine cases were adenomas, with severe dysplasia in five of
      them. Fourteen cases that were cytologically negative with minimal glandular
      atypia showed seven adenomas and seven nonneoplastic lesions on biopsy. Forty
      cases negative for malignant cells showed 19 adenomas and 21 nonspecific changes
      in the biopsy examination. CONCLUSION: Colonoscopic brushing cytodiagnosis is a
      sensitive technique for the detection of colorectal cancer. The combination of
      brushing cytology and biopsy improves the accuracy of diagnosis.

PMID- 9167676
TI  - DNA ploidy and proliferating cell nuclear antigen image analysis of peritoneal
      and pleural effusions. A possible diagnostic role.
AB  - OBJECTIVE: To determine the role of DNA and proliferating cell nuclear antigen
      (PCNA) image analysis (IA) in enhancing the diagnostic sensitivity of
      conventional cytology (CC). STUDY DESIGN: The histopathologic and clinical data
      on 87 consecutive pleural and peritoneal effusions were used to evaluate the
      accuracy of CC and DNA IA results. RESULTS: CC showed a sensitivity, specificity,
      positive predictive value (PPV) and negative predictive value (NPV) of 65%, 100%,
      100% and 62%, respectively. Aneuploidy peaks were seen in 49 cases; 47 of them
      were true positives. Thirty of 38 diploid cases were true negatives. The
      sensitivity, specificity, PPV and NPV were 85%, 94%, 96% and 80%, respectively.
      There were positive correlations between DNA ploidy profile and PCNA
      proliferative index (PI), (R = .697) and significant differences in PCNA PI
      between malignant and benign effusions (P < .001). CONCLUSION: The DNA IA PI by
      PCNA can be used as a complementary diagnostic tool with CC in cytologically
      inconclusive cases.

PMID- 9167677
TI  - Fine needle aspiration biopsy in hepatic Echinococcus multilocularis.
AB  - OBJECTIVE: To determine the fine needle aspiration biopsy (FNAB) findings in
      hepatic Echinococcus multilocularis. STUDY DESIGN: FNAB and tru-cut liver needle
      biopsy were applied in 14 hepatic E multilocularis cases. Cytologic smears were
      stained with May-Grunwald-Giemsa and periodic acid-Schiff (PAS) stain. Tissue
      sections were stained with hematoxylin-eosin (HE) and PAS stain. RESULTS: In
      tissue sections, homogeneous, thin, cystic structures of various dimensions
      strongly stained with PAS. Mucoid material was stained with PAS in the cystic
      structures. Wide, coagulative necrosis was observed in all cases. In some cases
      there were foreign body-type giant cells at the periphery of the lesion. In all
      the cytologic smears there were an intense necrotic ground, PAS-positive hyaline
      cuticular structures and mucoid globules; in some cases there were foreign body
      type giant cells. CONCLUSION: The above cytologic characteristics are basic
      diagnostic criteria for FNAB of E multilocularis.

PMID- 9167678
TI  - Toxoplasma lymphadenitis. Analysis of cytologic and histopathologic criteria and
      correlation with serologic tests.
AB  - OBJECTIVE: To identify cases of Toxoplasma lymphadenitis by light microscopic
      examination of fine needle aspiration cytology (FNAC) smears and paraffin
      sections and to correlate the result with those of serologic tests. STUDY DESIGN:
      The study group consisted of 19 cases of Toxoplasma lymphadenitis, 7 of which
      were diagnosed by FNAC, 9 on excision biopsy and 3 on FNAC followed by biopsy.
      Nineteen cases of reactive lymphadenitis, tuberculosis and infectious
      mononucleosus composed the control group. Sera from all 38 patients were screened
      for antibodies to Toxoplasma. RESULTS: Eleven of 19 cases (58%) of Toxoplasma
      adenitis had very high titers of antibody (> 300 ELISA units/ml), and 6 cases
      (31%) had antibody titers in a range suggestive of active infection (210-300
      ELISA units/mL) and required demonstration of rising titers. Overall, 89% of
      patients with Toxoplasma lymphadenitis showed significant levels of antibody. All
      patients from the control group showed consistently low levels of antibody to
      Toxoplasma. CONCLUSION: Though serologic tests are mandatory for the diagnosis of
      Toxoplasma lymphadenitis, a high index of suspicion can be obtained by means of
      light microscopy alone.

PMID- 9167679
TI  - Predictive value of fine needle aspiration cytology of bone lesions.
AB  - OBJECTIVE: To determine the predictive value of fine needle aspiration cytology
      (FNAC) of bone lesions. STUDY DESIGN: The study consisted of data retrieval on
      200 cases of bone lesions and their cytohistopathologic correlation to assess the
      diagnostic efficacy of FNAC in these cases, considering histopathology as the
      gold standard. The diagnostic indices were calculated by a decision matrix
      comparison. RESULTS: On cytohistopathologic correlation of 200 cases, 106 (53.0%)
      were malignant bone tumors (MBT): 97 primary and 9 metastatic; and 76 were benign
      bone lesions (BBL), 58 neoplastic (29%) and 18 nonneoplastic (9%). The aspirated
      material was adequate in 181 cases, whereas in 18 cases cytohistopathologic
      examination revealed no bony lesion. Thus, there were 163 evaluable cases, of
      which the specific morphologic diagnoses on FNAC were possible in 141 cases
      (86.5%), with a solitary false positive and 8 false negatives. The percentage of
      inadequate aspirates was more with BBL (13.2%) than MBT (8.5%). The overall
      diagnostic accuracy and sensitivity of bone lesions were 95.0%, whereas
      specificity, positive predictive value (PPV) and negative predictive value (NPV)
      were 94.7%, 99.4% and 69.2%, respectively. The sensitivity of FNAC was better
      (95.8%) with MBT as compared to BBL (91.7%), whereas specificity and PPV were
      almost equal (98.8% and 99.2%) in both cases. The NPV in cases of BBL was higher
      (97.8%) than in MBT (95.2%). These diagnostic indices were calculated excluding
      the inadequate cases. CONCLUSION: High PPV and NPV indicate the reliability of
      FNAC for the diagnosis of bone lesions.

PMID- 9167680
TI  - Leukemia cutis. Fine needle aspiration findings.
AB  - OBJECTIVE: To aspirate, for cytologic study, skin nodules from known cases of
      leukemia during full remission. STUDY DESIGN: The study group consisted of nine
      leukemia patients in full remission who developed skin nodules on the head, face,
      chest and upper extremities. RESULTS: The size of the nodules ranged between 1
      and 3.5 cm. The nodules were aspirated with 21-gauge needle. Four were diagnosed
      as acute lymphoblastic leukemia, 1 as chronic lymphocytic leukemia, 1 as acute
      myeloblastic leukemia, 2 as acute monocytic leukemia and 1 as acute promyelocytic
      leukemia. Histologic sections were diagnosed as lymphoma-leukemia. The patients
      developed leukemia again three to four months after excision of the skin nodules.
      CONCLUSION: Fine needle aspiration cytology is useful in the diagnosis of
      leukemia cutis.

PMID- 9167681
TI  - Tall cell variant of papillary thyroid carcinoma. A cytohistologic correlation.
AB  - OBJECTIVE: To identify the cytologic characteristics of the tall cell variant of
      papillary thyroid carcinoma in fine needle aspiration biopsies and make a
      cytohistologic correlation. STUDY DESIGN: The study group consisted of six
      patients subjected to fine needle aspiration biopsy of the thyroid prior to
      surgical resection of the tumor. RESULTS: Nineteen cases of the tall cell variant
      were identified in 229 cases of papillary thyroid carcinoma (8.5%) from 1957 to
      1993. Six cases had aspirates with tall cells. The patients were females with a
      median age of 43 years, and all had aggressive neoplastic diseases. The tumors
      had > 30% tall cells. The fine needle aspiration biopsy findings included nuclear
      grooves and abundant oxyphilic cytoplasm (100%), pseudonuclear inclusions (83.3%)
      and ground glass chromatin (67%). The majority of neoplastic cells had a
      nuclear/cytoplasmic ratio of 1:2. A tadpole shape was observed in noncohesive
      cells, and a respiratory epithelium-like arrangement was seen in cohesive cells.
      CONCLUSION: Fine needle aspiration biopsy is the best method of identifying tall
      cells preoperatively. Nuclear and cytoplasmic changes should be added to make a
      firm diagnosis of the tall cell variant and to rule out columnar cell carcinoma
      or squamous metaplasia in goiter or usual thyroid papillary carcinoma.

PMID- 9167682
TI  - Thyroid nodules. Role of fine needle aspiration and intraoperative frozen section
      examination.
AB  - OBJECTIVE: To determine the accuracy of fine needle aspiration (FNA) and
      intraoperative frozen section examination (IFSE) on thyroid nodules. STUDY
      DESIGN: The study group consisted of 470 patients who underwent thyroidectomy.
      FNA was performed on 289 patients and IFSE on 326. The FNA and IFSE results were
      compared with the final histologic diagnosis obtained after examination of
      permanent sections. RESULTS: The overall FNA sensitivity was 65%, specificity 88%
      and positive predictive value 61%. The IFSE sensitivity was 50%, and the
      specificity and positive predictive value were 100%. When both procedures were
      used together, FNA identified 16 of 45 (36%) carcinomas as malignant and an
      additional 13 (29%) as follicular proliferative lesions; IFSE correctly
      identified only 23 of 45 (51%) carcinomas. CONCLUSION: FNA provides enough
      information for determining the extent of thyroid surgery when a diagnosis of
      cancer is made. However, IFSE should be considered a supplementary procedure when
      FNA is not positive for cancer.

PMID- 9167683
TI  - Diagnosis from thyroid aspirates. Is the cytopathologist handicapped if not fully
      informed about the patient?
AB  - OBJECTIVE: When fine needle aspiration cytology (FNA) of the thyroid is performed
      as a first-line test, the cytopathologist cannot be fully informed about the
      patient's data. The authors investigated whether this decreases the accuracy of
      FNA and results in consequences for the patient. STUDY DESIGN: FNA smears of 202
      patients, 190 with benign and 12 with malignant thyroid disease, were
      reevaluated, supplying the cytopathologist first with only information from the
      case history known already at the initial admission, and subsequently with full
      data. RESULTS: The FNA diagnoses were corrected in 13 cases; in 8/13 they showed
      a more serious finding. The therapeutic modality was changed in only one case. No
      corrections were made in the ultimately malignant cases. CONCLUSION: In several
      cases the cytopathologist may be handicapped by receiving only partial
      information about the patient, but in our patients this had no demonstrable
      adverse consequences. Thus, FNA can be performed upon patient's admission.

PMID- 9167684
TI  - Thyroid follicular neoplasms diagnosed by high-resolution ultrasonography with
      fine needle aspiration cytology.
AB  - OBJECTIVE: To investigate the final results of cases with preoperative diagnoses
      of thyroid follicular neoplasms by fine needle aspiration cytology (FNAC). STUDY
      DESIGN: A retrospective review of 6,499 patients who received thyroid
      ultrasonography with FNAC at Chang Gung Memorial Hospital. Among 6,499 patients,
      209 (3.2%) were diagnosed by FNAC as having follicular neoplasms, of which 84
      received surgical treatment. Eighty-two of the 84 cases had a frozen section
      prepared during the operation. RESULTS: Thyroid malignancy was confirmed
      histopathologically in 164 cases. Among 84 thyroid follicular neoplasm patients,
      21 cases were diagnosed as malignant tumors, including papillary thyroid
      carcinoma, follicular thyroid carcinoma, medullary thyroid carcinoma and
      Hurthle's cell carcinoma. Ultrasonography on these 21 patients revealed that 16
      cases (76.2%) had low echo density in the thyroid nodule. The percentage was
      statistically significantly different from that in benign cases, 23.8% (P < .05).
      A higher incidence of malignancy was found in males, but the data did not reach
      statistical significance (P = .0586). CONCLUSION: Most of the follicular
      neoplasms revealed by FNAC were benign lesions. Low echo density on
      ultrasonography and male sex carried a higher risk of malignancy.

PMID- 9167685
TI  - Fine needle aspiration cytodiagnosis of primary and metastatic squamous cell
      carcinoma of the breast.
AB  - OBJECTIVE: To assess the diagnosis of squamous cell carcinoma involving the
      breast by fine needle aspiration cytology in four cases (two primary and two
      metastatic). STUDY DESIGN: All patients were women between the ages of 42 and 74
      years. The aspiration findings were confirmed by cell blocks of the aspirates,
      biopsy and/or comparison of the tissue from the previous primary. The aspirate
      was obtained using multiple passes in the breast masses while maintaining
      negative pressure. RESULTS: The cytohistologic features in all cases were
      characterized by numerous malignant squamous cells with hyperchromatic, enlarged,
      dense nuclei; thickened nuclear membranes; coarse chromatin; abundant
      eosinophilic, keratinizing glassy cytoplasm; and a necrotizing background with
      keratin debris. The diagnostic value of immunocytochemical study was considered
      questionable despite immunopositivity for cytokeratin and epithelial membrane
      antigen and negative staining for carcinoembryonic antigen and B72.3 in all
      cases. CONCLUSION: The identification of malignant squamous cells in breast
      aspirates is an important observation. Such cells, when seen as the predominant
      ones in an aspirate, should prompt a search for other sources of a primary tumor
      before a diagnosis of squamous cell carcinoma of the breast is accepted.

PMID- 9167686
TI  - Histologic assessment of equivocal cytologic smears.
AB  - OBJECTIVE: To determine if the conversion of equivocal cytologic smears into
      histologic sections would provide additional diagnostic information in those
      cases in which it was difficult to obtain additional cytologic samples. STUDY
      DESIGN: Over a year, eight equivocal cytologic smears were converted to
      histologic sections by removing the coverslips, rehydrating the smears, scraping
      off the smears into centrifuge tubes, making cell blocks, and sectioning and
      staining the blocks. RESULTS: The histologic sections enabled cell patterns to be
      studied and special staining (including immunoperoxidase studies) to be
      performed. In the eight cases studied, the additional information provided by
      histology led to a definitive diagnosis in six (75%). CONCLUSION: When cytologic
      findings are equivocal and it is difficult to obtain additional cytologic
      samples, conversion of the smears into histologic sections may provide additional
      information for diagnosis.

PMID- 9167687
TI  - Cytohistologic correlation of nuclear grade in breast carcinoma.
AB  - OBJECTIVE: To compare the nuclear grade (NG) in cytologic material (CNG) obtained
      from breast fine needle aspiration biopsies (FNABs) with the NG observed in
      surgical biopsies (BNG) of the same tumors. STUDY DESIGN: The study group
      consisted of 135 breast carcinomas with both FNAB and biopsy. Most of them were
      invasive ductal carcinomas. Cytologic aspirates and tissue sections were graded
      simultaneously by the three authors using a multiheaded microscope. Fisher's
      modification of Black's nuclear grading scheme was used. RESULTS: There was
      agreement between CNG and BNG in 70.37% of tumors. The percentage coincidence was
      slightly greater for NG 3. CONCLUSION: Nuclear grade can be easily established on
      FNAB. The lack of correlation (29.63%) may have been due to tumor heterogeneity
      and observer subjectivity when assigning nuclear grade.

PMID- 9167688
TI  - Fine needle aspiration biopsy of breast lesions and histopathologic correlation.
      An analysis of 837 cases in four years.
AB  - OBJECTIVE: To correlate fine needle aspiration biopsy (FNAB) and histopathology
      in 837 cases. STUDY DESIGN: A study consisting of 837 FNABs of breast lesions and
      their histopathologic correlation was conducted at Goa Medical College Hospital,
      Bambolin, Goa, India, over a period of four years, from January 1987 to December
      1990. Six hundred cases were followed with excision biopsy/mastectomy, and a
      cytohistologic correlation was established. The diagnostic accuracy of this
      series was assessed and compared with data obtained from the Indian and
      international literature. RESULTS: The diagnostic accuracy of this series
      (sensitivity 93.80%, specificity 98.21%, predictive value of a positive result
      92.70%, efficiency 97.40%) was compared with that in published reports.
      Statistically significant differences were found between the levels of diagnostic
      accuracy in series published by pathologists who diagnosed smears prepared by
      clinicians and surgeons (group A) and series published by pathologists who
      performed palpation and aspiration and made the cytologic diagnosis themselves
      (group B). These differences consisted mainly of a lower number of false
      positives and unsatisfactory samples in group B. CONCLUSION: Fine needle
      aspiration biopsy is an effective modality for the diagnosis of breast lesions.
      Lower rates of false positive and false negative diagnosis are achieved if the
      cytopathologist has personally performed the FNAB, prepared the smears and
      performed the microscopic interpretation. The diagnostic accuracy achieved with
      direct smear preparation is as good as that obtained by the newer Cytospin method
      for FNAB.

PMID- 9167689
TI  - Expression of pS2 protein and estrogen and progesterone receptor status in breast
      cancer.
AB  - OBJECTIVE: To investigate pS2 protein expression and estrogen (ER) and
      progesterone receptor (PR) status of imprints from surgical biopsies of breast
      cancer cases in relation to the histologic grade of malignancy. STUDY DESIGN: The
      study group consisted of 50 cases of primary breast carcinomas. For the
      demonstration of pS2 protein expression an immunocyto-chemical avidin-biotin
      complex technique was applied. Monoclonal antibody pS2 was used as the primary
      antibody, diaminobenzidine as the chromogene and hematoxylin as the counterstain.
      For the evaluation of ERs and PRs, a biochemical method was applied. RESULTS:
      Sixty-two percent of breast cancer cases showed positive expression of pS2. Of
      the 31 pS2+ cases, 74% had positive ERs and PRs. A statistically significant
      difference was observed between pS2 protein expression, ER+, PR+ and histologic
      grade of malignancy (P < .001). CONCLUSION: Two groups of breast cancer cases can
      be distinguished: one group that is ER+, PR+ and pS2+, with low malignancy
      potential, and another group that is ER-, PR- and pS2-, with high malignancy
      potential.

PMID- 9167691
TI  - Benign pairs. A useful discriminating feature in fine needle aspirates of the
      breast.
AB  - OBJECTIVE: To determine the diagnostic utility of the finding of naked, bipolar
      nuclei in fine needle aspirates of breast lesions. STUDY DESIGN: Aspirate smears
      from 150 cases of histologically proven benign (77) and malignant (73) breast
      lesions were evaluated for the presence of stripped, bipolar nuclei in the smear
      background as singlets as well as closely associated pairs. RESULTS: The presence
      of such pairs was a more specific indicator of benign entities (present in 70% of
      benign lesions vs. 1% of carcinomas) when compared to single, bare nuclei alone
      (present in 94% of benign lesions vs. 45% of carcinomas). Large numbers of such
      "benign pairs" also strongly favored the diagnosis of fibroadenoma within the
      benign subgroup. CONCLUSION: The presence of bipolar nuclear pairs is a valuable
      addition to the finding of singlets in the diagnosis of benign breast lesions and
      their subclassification.

PMID- 9167692
TI  - Cytology of granulomatous mastitis.
AB  - OBJECTIVE: To examine the cytologic features of granulomatous mastitis. STUDY
      DESIGN: Cytologic features of granulomatous mastitis (GM) are described as found
      on retrospective analysis of hematoxylin and eosin (H&E)-stained smears of nine
      breast lesions: eight fine needle aspiration biopsies and one imprint smear. All
      nine lesions were histologically confirmed. RESULTS: The aspirates were moderate
      or abundant. The H&E smears showed a distinctly inflammatory background with
      multinucleated giant cells (both foreign body and Langhans type), debris,
      neutrophils, macrophages, epithelioid cells and reactive epithelial cells.
      Special histochemical stains did not reveal any specific organisms. No foamy
      cells or caseation was seen. The four patients who presented for follow-up were
      free of disease after a minimum of 6 and maximum of 38 months. CONCLUSION:
      Although there are many entities mimicking GM, the cytologic pattern--consisting
      of multinucleated giant cells, debris, neutrophils, macrophages, epithelioid
      cells and reactive epithelial cells in the absence of foamy cells, caseation and
      demonstrable organisms--should prompt a diagnosis of GM.

PMID- 9167690
TI  - Intermediate filament expression of ductal carcinoma cells in fine needle
      aspirates of the breast.
AB  - OBJECTIVE: To assess the frequency of occurrence of vimentin expression in fine
      needle aspirates of ductal carcinoma of the breast and the association of
      vimentin expression with established prognostic indicators. STUDY DESIGN:
      Cytocentrifuge preparations made from fine needle aspirates of 51 cases of ductal
      carcinoma were studied. RESULTS: Vimentin expression, detected in 61% of cases,
      was positively associated with tumor size, lymph node status, tumor grade, growth
      fraction and negative estrogen receptor status, but only in the case of lymph
      node status did the association reach the level of statistical significance.
      CONCLUSION: Vimentin expression can be detected in breast cancer using fine
      needle aspiration. Further study is necessary to determine whether it provides
      independent prognostic information.

PMID- 9167693
TI  - The case for cytologic follow-up after LEEP.
AB  - OBJECTIVE: To examine our loop electrocautery excisional procedure (LEEP) biopsy
      experience to assess the incidence of abnormal follow-up and relate this to
      margin status. STUDY DESIGN: Records of 162 LEEP procedures performed between
      January 1992 and April 1994 were reviewed to evaluate margin readability and
      status. All follow-up cytologic or histologic specimens were examined. RESULTS:
      After a mean 10.9-month follow-up, of 162 cases, 67 had a negative study (41.4%).
      Fifty-four (33.3%) had an abnormal result, with high grade squamous
      intraepithelial lesion (HSIL) in 16 cases (13.2%) of all LEEPs with follow-up,
      low grade squamous intraepithelial lesions in 27 (22.3%) and squamous atypia in
      11 (9.1%). On microscopic review of these 54 cases, 37 had a readable margin
      (68.5%); of these readable margins, 12 (32.4%) were positive. Forty-one cases
      (25.3% of all LEEPs) had no follow-up study. CONCLUSION: The high incidence of
      HSIL after LEEP highlights the need for vigilant follow-up. Prediction of follow
      up by margin status is dubious. Thermal artifact makes the margin uninterpretable
      in many cases, and two-thirds of cases with abnormal follow-up occurred where the
      LEEP margin was negative. Our finding of no follow-up for 25% of LEEPs performed
      is particularly disturbing in light of these results.

PMID- 9167694
TI  - Fine needle aspiration biopsy of hepatic leiomyosarcoma. An unusual epithelioid
      variant posing a potential diagnostic pitfall in a hepatocellular carcinoma
      prevalent population.
AB  - OBJECTIVE: To study the cytomorphologic features of hepatic smooth muscle tumors
      on fine needle aspiration biopsy (FNAB) material in a hepatocellular carcinoma
      (HCC)-prevalent population, in which a potential diagnostic pitfall is an unusual
      variant of metastatic epithelioid leiomyosarcoma seen on aspiration cytology.
      STUDY DESIGN: FNABs of five cases of metastatic hepatic leiomyosarcomas were
      studied cytohistologically and immunocytochemically. In addition, ultrastructural
      studies were performed in one unusual case. Resected hepatic specimens and all
      other relevant histopathologic specimens were reviewed. RESULTS: Classically,
      aspirates of leiomyosarcoma produced syncytial masses of spindle cells
      characterized by overlapping, cigar-shaped nuclei and truncated ends. An unusual
      variant of metastatic epitheliod leiomyosarcoma was studied, with cytohistologic,
      immunohistochemical and ultrastructural correlation. CONCLUSION: Hepatic spindle
      cell lesions consist mainly of metastatic leiomyosarcomas. The diagnosis of
      malignancy and metastatic status of hepatic smooth muscle tumors is facilitated
      by the presence of an extrahepatic primary tumor. In a hepatitis B virus-endemic
      population, HCC, sarcomatoid type, has to be considered in the differential
      diagnosis of hepatic spindle cell lesions and the classic type, in epithelioid
      variants of smooth muscle tumors.

PMID- 9167695
TI  - Image analysis of nuclear/cytoplasmic ratio in cervical smears to discriminate
      three grades of cervical intraepithelial neoplasia.
AB  - OBJECTIVE: To suggest which system of cytologic classification (Bethesda System
      or World Health Organization [WHO]) of cervical lesions is more adequate for the
      Public Health Service of Sao Paulo State, Brazil, based on morphometric study
      with the Jandel Videoanalysis (JAVA) System. STUDY DESIGN: The study comprised
      groups of typical smears: cervical intraepithelial neoplasia (CIN 1) separated
      into two subgroups: cytopathic effects of human papillomavirus associated or not
      with dyskaryosis, CIN 2 and CIN 3. The JAVA system of image analysis was used to
      determine the nuclear/cytoplasmic (N/C) ratio in abnormal cells from each group.
      RESULTS: Significant differences were detected between the three grades of CIN
      and between the two subgroups of CIN 1. CONCLUSION: Although image analysis is
      not applicable to large-scale population screening of cervical smears, its use in
      the present study favored the three-grade cytologic classification (WHO). In
      addition, the three-grade classification offers the clinician more options for
      treatment. Considering the clinical-laboratory characteristics of our public
      health service, the three-grade classification is more adequate.

PMID- 9167696
TI  - A self-administered device for cervical cancer screening in northeast Thailand.
AB  - OBJECTIVE: To test a self-scraping device as a mass screening device against a
      routine scraping method and to evaluate the acceptance of the self-scraping
      device by a group of rural females from Northeast Thailand. STUDY DESIGN: From a
      rural area of Northeast Thailand, 552 women were trained and motivated, through
      primary health care structures, to participate in a cervical cancer screening
      exercise using a self-scraping device. After one week, the same females were
      reexamined by gynecologists using the routine scraping method. In both cases the
      specimens were stained according to Papanicolaou. Through questionnaires the
      acceptance of the self-scraping device was evaluated. RESULTS: Through the self
      scraping method, 13 cases suspicious for malignancy were detected. Specimens
      obtained through examination by physicians confirmed 11 cases to be suspicious
      for malignancy. No false negative cases were found. In the detection of
      inflammation, the self-scraping method was not as accurate as examination by a
      physician. The device was accepted by the females who participated in the study.
      CONCLUSION: In the rural areas of developing countries, where physicians and
      other trained medical personnel are not often available to carry out regular
      screening tests on a population basis, the self-scraping method can be applied as
      an integral part of primary health care for mass screening for uterine cervical
      cancer.

PMID- 9167697
TI  - Value of Gram's stain of cell block material from peritoneal fluid in bacterial
      peritonitis.
AB  - OBJECTIVE: To determine the value of Gram's stain of cell blocks of peritoneal
      fluid for the diagnosis of bacterial peritonitis. STUDY DESIGN: The results of
      Gram's stain of 12 cases of culture-positive, frank bacterial peritonitis (FBP)
      and 11 cases of culture-positive spontaneous bacterial peritonitis (SBP) were
      compared with 6 cases of culture-negative frank sterile peritonitis and 21 cases
      of culture-negative spontaneous sterile peritonitis. RESULTS: For both FBP and
      SBP, Gram's stain had low sensitivity (8% and 9%). Overall, the positive
      predictive value of Gram's stain for peritonitis was 33%. Hematoxylin-eosin (HE)
      was just as sensitive but had a positive predictive value of 100%. CONCLUSION: In
      cell block material of peritoneal fluid, Gram's stain is of little value except
      to further characterize organisms seen on HE.

PMID- 9167698
TI  - Diagnosis of small non-cleaved cell lymphoma by fine needle aspiration utilizing
      cytomorphologic features combined with cytogenetic analysis.
AB  - OBJECTIVE: To determine the utility of cytogenetic studies in the diagnosis of
      small non-cleaved cell lymphoma by fine needle aspiration. STUDY DESIGN: Cases of
      suspected lymphoma were identified in a prospective fashion by an immediate
      examination of the fine needle aspirate material by the pathologist. In these
      instances, additional material was aspirated directly into RPMI 1640 medium for
      cytogenetic studies. RESULTS: Four cases of suspected small non-cleaved cell
      lymphoma were identified on fine needle aspirate material, and the diagnosis was
      confirmed in all cases by the presence of the characteristic (8;14) translocation
      or associated variant translocation in cytogenetic studies from the aspirated
      material. CONCLUSION: Cytogenetic analysis is useful as an additional ancillary
      technique applicable to fine needle aspiration material. In the case of suspected
      small non-cleaved cell lymphoma, the finding of a translocation (8;14) or
      associated variant translocation, along with the characteristic cytomorphology,
      allows a definitive diagnosis by fine needle aspiration and may alleviate the
      need for biopsy.

PMID- 9167699
TI  - Early biologic behavior of bone grafts. A fine needle aspiration cytology study.
AB  - OBJECTIVE: To conceptualize, with fine needle aspiration cytology (FNAC), the
      early cellular events occurring in and around fresh autogenous and allogenic bone
      grafts during the first 40 postimplantation days. STUDY DESIGN: Forty-eight cases
      of bone grafts were studied by FNAC at serial intervals of 10, 20, 30 and 40
      postimplantation days. Twenty patients were recipients of autogenous grafts, 16
      received 0.6N HCI partially decalcified allogenic bone implants, and 4 received
      combined autogenous and allogenic bone grafts (included in the allograft group).
      There were eight control cases of closed fracture shaft femur, which were managed
      conservatively. RESULTS: The initial cellular responses in autogenous grafts,
      allografts and controls appear to be a part of the nonspecific reparative process
      followed by a more specific phase, with a steady increase in relative lymphocyte
      count from the 20th day onwards. Osteogenesis, as judged by osteoblasts and
      osteoclasts, was also comparable. CONCLUSION: Partially decalcified allografts
      appear to be a good substitute for autogenous bone grafts in clinical practice
      when adequate autogenous material is not available. FNAC is a good technique for
      studying bone graft responses without interfering with graft uptake. It is
      helpful in the early detection of subclinical infection or any other pathology at
      the graft site.

PMID- 9167700
TI  - Cytology of pilomatrixoma (calcifying epithelioma of Malherbe) in fine needle
      aspirates.
AB  - OBJECTIVE: To characterize the cytomorphologic features of pilomatrixoma. STUDY
      DESIGN: Aspirate findings in nine cases of PMX were correlated with clinical data
      and subsequent histology. This relatively large volume of case material afforded
      an opportunity to test the cytologic criteria that have been proposed as
      diagnostic of pilomatrixoma in the case reports published previously. RESULTS:
      Ghost cells, basaloid cells and calcium deposits were the features found to be
      most characteristic of PMX and were observed in all four cases in which a correct
      diagnosis was made originally. CONCLUSION: The presence of ghost cells seems to
      be the key to recognizing PMX. These cells are visible in the majority of air
      dried smears but seldom in alcohol-fixed smears. Adequate cytologic sampling and
      the routine use of both wet-fixed and air-dried smears should preclude an
      incorrect diagnosis.

PMID- 9167701
TI  - False negative rate. A misnomer, misunderstood and misused.
AB  - By rigorous statistical standards, the expression false negative rate is a
      misnomer because the concept of "rate" is associated with the rapidity of change
      of phenomena per unit of time or other variable (e.g., temperature). Uncertainty
      about the term false negative rate resulted in the introduction of similar but
      equally dubious expressions, including false negative fraction and miss rate. The
      statistically correct term in the practice of cytopathology is false negative
      proportion because we have here a fraction in which the numerator (number of
      false negative cases) is a part of the denominator (number of true positive cases
      plus number of false negative cases). This is the classic definition of the term
      proportion.

PMID- 9167702
TI  - Frequency of tumor diathesis in smears from women with squamous cell carcinoma of
      the cervix.
AB  - OBJECTIVE: To determine the prevalence of tumor diathesis (TD) in cervicovaginal
      smears from patients with squamous cell carcinoma (SQC). STUDY DESIGN: We
      reviewed all the cervical smears obtained no more than one year before a biopsy
      diagnosis of SQC. Patients who underwent irradiation to the cervix before the
      smear was taken were excluded from the analysis. The smears were rescreened by
      both authors, and the presence and extent of TD were recorded. RESULTS: Twenty
      eight smears from 19 patients with SQC fulfilled the study criteria. TD was seen
      in 15 of the 28 smears (54%). There was a positive correlation between the
      presence of TD and the depth of invasion. CONCLUSION: Although an important
      criterion of malignancy, TD is absent from some cases of SQC, particularly those
      that invade < 5 mm. A definite distinction between an intraepithelial lesion and
      a shallow invasive cancer may not be possible on cervicovaginal smears.

PMID- 9167703
TI  - Fine needle aspiration cytology of pleomorphic adenoma. An analysis of 212 cases.
AB  - OBJECTIVE: To assess the value of fine needle aspiration cytology (FNAC) in the
      diagnosis of pleomorphic adenoma and to determine the cytologic variations
      responsible for diagnostic errors. STUDY DESIGN: We retrospectively studied 212
      cases cytologically diagnosed as pleomorphic adenoma. In 184 a histologic
      diagnosis was available. Fourteen cases of histologically proven pleomorphic
      adenomas with a previously erroneous cytologic diagnosis were also reviewed. This
      study was based on those cases with a histologic diagnosis. RESULTS: The
      sensitivity and specificity of the cytologic diagnosis of pleomorphic adenoma in
      our series were 92.6% and 98.4%, respectively. In relation to malignancy, the
      series showed six false negative and three false positive diagnoses. In those
      cases correctly diagnosed on aspiration (175), a typical cytologic appearance,
      with no diagnostic difficulties, was observed in 118 cases (67.4%); the remainder
      showed cytologic variations. Cellular atypia (20.6%), cystic transformation (7%)
      and the presence of a cylindromatous pattern (5%) resembling adenoid cystic
      carcinoma were the most common cytologic variations observed and responsible for
      the majority of the errors. CONCLUSION: The cytologic variations in FNAC of
      pleomorphic adenoma must be considered in order to avoid important errors in the
      preoperative management of and surgical approach to salivary gland lesions.

PMID- 9167704
TI  - Reverse transcriptase polymerase chain reaction for detecting Ewing's sarcoma in
      archival fine needle aspiration biopsies.
AB  - OBJECTIVE: Previous studies on pediatric soft tissue sarcomas have demonstrated a
      chromosomal 11;22 (q24;q12) translocation in Ewing's sarcoma (ES) and peripheral
      primitive neuroectodermal tumors that appears to be a unique oncogenic marker. To
      investigate the usefulness of reverse transcriptase polymerase chain reaction (RT
      PCR) as an ancillary method for cytodiagnosis, we tested archival aspirates
      derived from ES patients to establish whether any beta-actin RNA expression or
      tumor-specific EWS/FLI-1 gene translocation had occurred. STUDY DESIGN: Sixteen
      skeletal specimens aspirated 10-15 years earlier from patients with cytologic and
      histologic diagnoses of ES were prepared for PCR. The amplification products were
      sequenced. RESULTS: Amplifiable RNA was detected in smears from 12 patients by
      beta-actin RT-PCR. Seven aspirates from beta-actin-positive patients showed ES
      specific genomic translocation (58%). Sequence analysis of the resulting PCR
      fragments revealed EWS/FLI-1 fusion transcriptions of varying length. CONCLUSION:
      When RNA was retrievable, RT-PCR applied to routinely stained aspirate smears was
      a highly specific method in differential diagnosis of ES.

PMID- 9167705
TI  - Fine needle aspiration cytology of metastatic olfactory neuroblastoma.
AB  - OBJECTIVE: Olfactory neuroblastoma (ONB) is an uncommon malignant neoplasm that
      originates in the upper nasal cavity. Cytomorphologic descriptions of ONB have
      been limited to isolated case reports. The features of a series of metastatic ONB
      diagnosed by fine needle aspiration (FNA) are described. STUDY DESIGN: Cytologic
      findings in four patients with ONB metastatic to cervical lymph nodes who
      underwent FNA were reviewed, and the cytomorphologic findings were summarized.
      Immunocytochemical findings and ultrastructural features with selected
      immunoelectron microscopy from three cases are described. RESULTS: Aspiration
      cytology revealed a predominance of single cells with intermixed small, loosely
      cohesive, three-dimensional cell groups. Cell size was small to intermediate,
      with round nuclei. There was an overall monomorphic appearance, with minimal
      nuclear pleomorphism. Chromatin was finely granular and stippled, with multiple,
      small chromocenters. Cytoplasm in the cell groups had a fibrillary quality and
      was moderate in amount. Single nuclei were frequently stripped of cytoplasm.
      Occasional pseudorosettes were noted. Immunocytochemical stains were positive for
      both neuronspecific enolase and synaptophysin. Ultrastructural examination showed
      neuritic cell processes with neurosecretory granules and microtubules.
      Immunoelectron microscopy showed positive labeling of neurosecretory granules by
      chromogranin A. CONCLUSION: FNA cytomorphology, in combination with ancillary
      studies, can provide an accurate diagnosis of metastatic ONB.

PMID- 9167706
TI  - Utility of fine needle aspiration in HIV-positive patients with corresponding CD4
      counts. Four years' experience in a large inner city hospital.
AB  - OBJECTIVE: To assess the utility of fine needle aspiration (FNA) in human
      immunodeficiency virus (HIV)-positive patients with corresponding CD4 count
      analysis. STUDY DESIGN: The study group consisted of 108 FNA specimens from 80
      patients performed from January 1991 to December 1994. RESULTS: FNAs were sub
      typed into four categories: lymph nodes (59 specimens), masses (26 specimens),
      salivary glands (19 specimens) and breast (4 specimens). Thirty-three were
      diagnosed as reactive lymph nodes, 15% as benign lymphoepithelial lesions and 9%
      as granulomas; 9% revealed acute inflammation, 5% were positive for malignant
      lymphoma, and 3% were suspicious for Kaposi's sarcoma. Differences in CD4 counts
      were statistically significant for specific subsets of HIV-related illnesses.
      General trends were noted in mean CD4 counts for specific sub-groups of HIV
      related illnesses. CONCLUSION: Material adequate for culture can be obtained with
      the FNA procedure. FNA in skilled hands is a very useful simple and cost
      effective procedure for the diagnosis of HIV-related lesions and in the
      management of these patients. This study suggested that mean CD4 counts are
      statistically significant in specific subsets of HIV related illnesses.

PMID- 9167707
TI  - Cytologic diagnosis of peritoneal fluids. Applicability to the laparoscopic
      diagnosis of endometriosis.
AB  - OBJECTIVE: To determine the accuracy of cytologic examination of laparoscopically
      obtained peritoneal fluid in the diagnosis of endometriosis. STUDY DESIGN: This
      investigation analyzed 50 laparoscopic fluid specimens received over a three-year
      period. Retrospective cytologic findings were correlated with clinical history
      and laparoscopic diagnoses. Touch preparations were also collected from
      necropsies to develop cytologic criteria necessary to distinguish endometrial
      cells from mesothelial cells. RESULTS: The presence of hemosiderin-laden
      macrophages in peritoneal fluids was more specific but less sensitive than the
      presence of endometrial cells for the diagnosis of endometriosis. CONCLUSIONS: In
      women undergoing laparoscopy to detect endometriosis, the identification of
      endometrial cells alone in peritoneal fluids may not be sufficient to render a
      definitive diagnosis of endometriosis. However, the presence of hemosiderin-laden
      macrophages in this population should alert the cytologist to that possibility.

PMID- 9167708
TI  - Hodgkin's disease variant of Richter's syndrome. Report of a case with diagnosis
      by fine needle biopsy.
AB  - BACKGROUND: Chronic lymphocytic leukemia (CLL) with transformation into large
      cell lymphoma (Richter's syndrome) is a well-documented phenomenon. Only rarely
      does CLL terminate in Hodgkin's disease (HD) as Richter's syndrome. Reports of
      Hodgkin's variant of Richter's syndrome proven by histologic and immunohistologic
      evaluation have been published, but no cytologic reports of this entity exist.
      Distinguishing between large cell lymphoma and HD as variants of Richter's
      syndrome is essential because of recent reports of improved prognosis in HD.
      CASE: We report a case of a 65-year-old male previously diagnosed with CLL who
      subsequently developed fever, fatigue, an intraabdominal mass and enlarged
      periaortic lymph nodes. Fine needle biopsy (FNB) and immunophenotyping by flow
      cytometry of the mass revealed cytologic and immunophenotypical cells of CLL
      admixed with binucleate and multinucleate cells with prominant eosinophilic
      nucleoli consistent with Reed-Sternberg cells. CONCLUSION: This is the first
      reported case of HD variant of Richter's syndrome diagnosed by FNB. As FNB
      becomes more common in the follow-up of lymphoreticular diseases, cytologists
      should be aware of this unusual HD variant of Richter's syndrome.

PMID- 9167709
TI  - Fine needle aspiration cytology of amyloid goiter. A report of four cases.
AB  - BACKGROUND: Amyloid goiter is a very rare clinical entity. It can be confused
      easily with a neoplastic goiter both clinically and cytologically. CASES: In four
      cases of amyloid goiter the diagnosis was established preoperatively by fine
      needle aspiration cytology. Abundant violet to pink amorphous material with
      staining characteristics of amyloid was obtained in all cases. This material was
      morphologically distinct from colloid. Abdominal fat aspiration was done in all
      four cases. Two of the four abdominal fat aspirates were positive for amyloid.
      CONCLUSION: Attention to the morphology of cells accompanying amyloid allows
      exclusion of medullary thyroid carcinoma, thereby avoiding unnecessary surgery.
      Moreover, aspirates from the abdominal pad of fat and the thyroid and salivary
      glands, when enlarged, are useful in the workup of suspected amyloidosis,
      especially since it is a safe, easily performed procedure.

PMID- 9167710
TI  - Intraoperative fine needle aspiration diagnosis of cardiac rhabdomyoma. A case
      report.
AB  - BACKGROUND: Cardiac rhabdomyoma is a very common benign tumor in infants and
      children. It can be confused clinically with a malignant tumor. CASE: A 6-year
      old girl was admitted with a chief complaint of breathlessness. Chest
      roentgenography revealed cardiomegaly. Echocardiography showed a right atrial
      mass. Intraoperative fine needle aspiration showed groups of large, polygonal
      cells with granular, vacuolated cytoplasm. Rarely were intranuclear inclusions
      observed. CONCLUSION: The cytologic findings were characteristic of rhabdomyoma.

PMID- 9167711
TI  - Angiosarcoma at unusual sites. A report of two cases with aspiration cytology and
      diagnostic pitfalls.
AB  - BACKGROUND: Angiosarcomas are uncommon soft tissue neoplasms with a predilection
      for skin and superficial soft tissues. CASES: Two cases of angiosarcoma occurred
      at unusual sites, the parotid gland and lung. The parotid lesion was
      characterized by malignant cells present singly, in loose groups, in tight three
      dimensional aggregates and in acinar formation initially misinterpreted as an
      adenocarcinoma. The lung mass showed malignant cells in association with vascular
      endothelium, suggestive of angiosarcoma. Both cases were negative for Ulex
      europaeus and Factor VIII-related protein but demonstrated strong
      immunopositivity for CD31, a highly specific endothelial marker. CONCLUSION: In
      the absence of vasoformative structures, important diagnostic pitfalls are
      pseudovascular adenoid squamous cell carcinoma, poorly differentiated
      adenocarcinoma, melanoma and lymphoma. Immunocytochemical studies and clinical
      history are essential to the correct diagnosis.

PMID- 9167712
TI  - Adult embryonal rhabdomyosarcoma metastatic to the breast and diagnosed by fine
      needle aspiration. A case report.
AB  - BACKGROUND: Metastasis to the breast from extra-mammary malignancies is rare, but
      its recognition is important. A solitary metastasis must be distinguished from
      the primary breast cancer because the treatment and prognosis are quite
      different. CASE: A 30-year-old female presented with a 4.0-cm, solitary,
      nontender mass in the upper outer quadrant of the right breast 11 months after
      primary surgery for maxillary sinus embryonal rhabdomyosarcoma. The
      cytomorphology revealed features of small round cell tumor. Immunocytochemical
      staining disclosed a positive reaction to vimentin and desmin and negative
      reaction to cytokeratin, confirming the diagnosis of rhabdomyosarcoma.
      CONCLUSION: Fine needle aspiration with ancillary studies is essential in the
      diagnosis of metastatic malignancy of the breast in order to avoid unnecessary
      mastectomy and to implement appropriate systemic therapy.

PMID- 9167713
TI  - Fine needle aspiration cytology of intramammary lymph nodes in an HIV-1-positive
      patient. A case report.
AB  - BACKGROUND: Although rare, intramammary lymph nodes can occur in any quadrant of
      the breast and display a variety of pathologic conditions. Intramammary lymph
      nodes may be detected by routine clinical examination, mammography or ultrasound
      or during gross surgical pathology examination of breast specimens. CASE: A 42
      year-old, black woman, HIV-1 positive, presented with bilateral mirror-image
      breast masses. Fine needle aspiration cytology ruled out the presence of
      malignancy and confirmed the diagnosis of benign, reactive intramammary
      lymphadenopathy. CONCLUSION: Clinicians and pathologists should be alert to the
      existence and potential importance of intramammary lymph nodes in the
      differential diagnosis of a breast mass in HIV-1-positive patients.

PMID- 9167714
TI  - Eccrine spiradenoma mimicking adenoid cystic carcinoma on fine needle aspiration.
      A case report.
AB  - BACKGROUND: Although the cytologic features of salivary gland tumors are well
      recognized, an adnexal skin tumor occurring in the same region, on occasion, may
      resemble and be confused with a salivary gland neoplasm. CASE: A case of eccrine
      spiradenoma presented as a painful mass in the region of the parotid that
      mimicked an adenoid cystic carcinoma on fine needle aspiration cytology.
      CONCLUSION: Fine needle aspirates of eccrine spiradenoma, a benign cutaneous
      adnexal tumor, may have findings that mimic those of adenoid cystic carcinoma.
      Both may have cell balls and rosettelike structures surrounding stromal matrix
      cores. Recognition of three cell types in eccrine spiradenomas, including
      epithelial cells, myoepithelial cells and lymphocytes, as compared to a single
      cell type in adenoid cystic carcinoma, is paramount in avoiding this potential
      pitfall in cytologic diagnosis.

PMID- 9167715
TI  - Granulomatous mastitis caused by sparganum. A case report.
AB  - BACKGROUND: Sparganosis is not a common disease, and its rarity makes it
      difficult to distinguish from others. Close examination of fine needle aspiration
      biopsy (FNAB) samples, however, can aid in histologic examination of the lesion.
      CASE: A 64-year-old female, born and raised in a rural area in the state of
      Goias, Brazil, presented with a relatively mobile and hard lump in the lower
      inner quadrant of the right breast. It was initially diagnosed as granulomatous
      mastitis, but cytologic examination of the surgical specimen revealed a sparganum
      larva, also revealed by anterior FNAB. CONCLUSION: Sparganum should be considered
      in the differential diagnosis of granulomatous mastitis, especially among Asians
      living in other countries.

PMID- 9167716
TI  - Crystallizing galactocele. A case report.
AB  - BACKGROUND: Galactoceles are benign cystic lesions that generally occur during
      pregnancy and postpartum lactation. Fine needle aspiration (FNA) yields milky
      fluid that is often both diagnostic and therapeutic. Cytologically, aspirates are
      generally noted to contain occasional foam cells and benign epithelium displaying
      lactational change with an abundant background of lipid micelles and
      proteinaceous material. CASE: A 23-year-old, black female presented with a 1.0
      cm, discrete, nontender nodule involving the upper middle area of the left
      breast. FNA showed crystals of varying size and shape, best viewed with Diff-Quik
      and demonstrating metachromasia, polarization and birefringence. They were also
      positive with periodic acid-Schiff stain and both alizarin red S and von Kossa
      stain for calcium. Scanning electron microscopy revealed angulated, well-defined
      geometric crystals often with scalloped edges and smooth surfaces. The internal
      structure of the crystals consisted of electron-lucent material without
      periodicity or lattice formation, as observed by transmission electron microscopy
      and x-ray diffraction. Electron probe microanalysis identified small quantities
      of calcium, chlorine, potassium and sulphur within the crystals. CONCLUSION: We
      think that in this case the crystals represented precipitation of inspissated
      lactational secretions. There are several possible mechanisms of precipitation.
      The differential diagnosis includes other breast lesions with acellular amorphous
      components that may be confused with crystallizing galactocele in FNA biopsy
      specimens.

PMID- 9167717
TI  - Cytologic features of sinus histiocytosis with massive lymphadenopathy. A report
      of three cases.
AB  - BACKGROUND: Sinus histiocytosis with massive lymphadenopathy (SHML) was described
      over 20 years ago by Rosai and Dorfman. Originally it was described as occurring
      in young males, predominantly with cervical lymphadenopathy. Since then over 423
      histologically documented cases of SHML have been documented, including many
      extranodal sites. Few studies have characterized the cytologic features of SHML.
      CASE: Three cases of lymph node involvement by SHML occurred, one also with skin
      involvement. Cytologic findings included numerous histiocytes with phagocytized
      lymphocytes, atypical forms of histiocytes and a reactive, lymphoid background.
      Surgical biopsy and immunohistochemical stain for S-100 protein of all three
      cases confirmed the cytologic impression. CONCLUSION: Sinus histiocytosis with
      massive lymphadenopathy can be diagnosed by cytology in conjunction with clinical
      history and immunohistochemistry.

PMID- 9167718
TI  - Fine needle aspiration cytology as a diagnostic approach to
      lymphangioleiomyomatosis. A case report.
AB  - BACKGROUND: Lymphangioleiomyomatosis is a rare condition in women of childbearing
      age that affects the lymphatic system, giving rise to blockage of the thoracic
      duct with chylothorax and chyloascites. The diagnosis is often delayed because
      the characteristic muscular proliferation may be missed by the pathologist. CASE:
      A 29-year-old female presented with lymphangioleiomyomatosis and bilaterally
      dermoid ovarian cysts. She had enlarged paraaortal and supraclavicular "lymph
      nodes" and pleural chylothorax on the left side. Fine needle aspiration cytology
      from the supraclavicular "lymph node" yielded clear, watery fluid containing
      groups of relatively large monomorphic spindle cells. The final diagnosis was
      possible after histopathologic examination of an excised paratubar lymph node.
      CONCLUSION: Lymphangioleiomyomatosis can be suggested by means of ultrasonography
      and fine needle aspiration cytology.

PMID- 9167719
TI  - Cytodiagnosis of a herniated disk presenting as a soft tissue mass. A case
      report.
AB  - BACKGROUND: Extraforaminal disk herniation has been recognized with increasing
      frequency. When the herniated disk (HD) fragment detaches and migrates away from
      the spinal column, it can be confused with other space-occupying paraspinal
      lesions. CASE: A 63-year-old female presented with right leg pain and weakness. A
      magnetic resonance image showed a right psoas muscle mass. Fine needle aspiration
      biopsy (FNAB) established a diagnosis of HD. CONCLUSION: The cytologic appearance
      of HD is characteristic. When correlated with clinical findings, the diagnosis of
      HD can be established by FNAB.

PMID- 9167720
TI  - Hyalinizing trabecular adenoma of the thyroid. A report of two cases with
      cytologic, histologic and immunohistochemical findings.
AB  - BACKGROUND: Hyalinizing trabecular adenoma (HTA) is a rare benign thyroid tumor
      that is easily confused with medullary carcinoma on surgical specimens and with
      papillary carcinoma on cytologic specimens. CASES: The fine needle aspiration
      biopsies (FNABs) and surgically resected specimens from two patients with HTA
      were studied. Nuclear grooves and nuclear pseudoinclusions were identified in
      both FNABs. Gross examination of the surgical specimens revealed two nodules (0.8
      and 0.5 cm in diameter) in one case and a 6-cm nodule in the other. A thin,
      fibrous capsule surrounded each nodule. A predominant trabecular pattern was
      observed in the three lesions. Antibodies to thyroglobulin, carcinoembryonic
      antigen (CEA), epithelial membrane antigen (EMA), vimentin, chromogranin,
      synaptophysin, neuron-specific enolase, proliferating cell nuclear antigen
      (PCNA), Ki-67 and p53 were used to stain 10% buffered, formalin-fixed, paraffin
      embedded sections of the surgical specimens. No immunostaining was observed with
      antibodies against calcitonin, synaptophysin, chromogranin, EMA, vimentin or p53.
      Less than 5% of cells were CEA positive in one case. The Ki-67 index was low and
      PCNA expression high. CONCLUSION: HTAs occur as solitary or multiple nodules.
      FNABs of HTAs contain cells with nuclear grooves and nuclear pseudoinclusions but
      lack psammoma bodies, high cellularity and papillary structures.
      Immunohistochemistry using anticalcitonin and antithyroglobulin antibodies is
      helpful in distinguishing these tumors from medullary carcinoma. The low Ki-67
      index and absence of p53 immunostaining are consistent with the benign behavior
      of this tumor. The significance of high PCNA immunostaining is uncertain.

PMID- 9167721
TI  - Rhinosporidiosis. Report of a case with an unusual presentation with bony
      involvement.
AB  - BACKGROUND: Rhinosporidiosis, a fungal infection due to Rhinosporidium seeberi,
      frequently produces polypoidal lesions in the nose. Sites like the conjunctiva,
      larynx, trachea, nasopharynx, skin and genitourinary tract are less frequently
      involved. Generalized rhinosporidiosis with skin and visceral involvement is
      extremely rare. This report describes the fine needle aspiration cytology (FNAC)
      of rhinosporidiosis occurring as a solitary lesion with erosion of cortical bone.
      CASE REPORT: FNAC of a soft tissue swelling overlying a lytic lesion on the
      anterior aspect of the tibia was performed in a 40-year-old male. Smears revealed
      numerous sporangia and spores of R seeberi. There were no mucocutaneous lesions.
      Histologic examination confirmed the bony involvement. CONCLUSION: The FNAC
      diagnosis of rhinosporidiosis is specific. Preoperative diagnosis is possible
      even in cases with unusual clinical presentations.

PMID- 9167722
TI  - Fine needle aspiration cytology of cystic hypersecretory carcinoma of the breast.
      A case report.
AB  - BACKGROUND: Cystic hypersecretory carcinoma (CHC) of the breast is a rare variant
      of intraductal carcinoma. It is characterized by a multicystic, yellow-brown
      lesion with gelatinous material grossly and cystically dilated ducts with an
      eosinophilic secretion microscopically. The histologic or cytologic features can
      be deceptively bland. CASE: A 37-year-old female presented with an 8-cm-diameter,
      firm mass in the breast. Radical mastectomy was performed after fine needle
      aspiration (FNA). The moderately cellular smear had a characteristic background
      of proficient, intensely staining secretion with bubbling. The cellular
      components were various, ranging from sheets of benign hyperplastic ductal cells
      to three-dimensional clusters or papillae of frankly malignant ductal cells, with
      varying degrees of secretory activity. The background consisted of inflammatory
      cells, naked nuclei and foamy histiocytes. The cytologic findings correlated well
      with the histologic features of the tumor, which showed both micropapillary
      intraductal carcinoma with apocrine metaplasia and focal high grade invasive
      carcinoma in a background of cystic hypersecretory hyperplasia. CONCLUSION: This
      was the first reported case of FNA cytology of an invasive form of CHC. CHC has
      characteristic features on FNA, and so a reliable diagnosis can be made.

PMID- 9167723
TI  - Atypical lipoma as a potential pitfall in the cytodiagnosis of subcutaneous
      tumors. A report of two cases.
AB  - BACKGROUND: If well-differentiated liposarcomas of lipomalike type occur in the
      subcutis, they behave as benign neoplasms. For these tumors the term atypical
      lipoma was introduced in 1975. Fine needle aspiration (FNA) findings in these
      tumors may raise a false impression of malignancy. CASES: Females aged 34 and 48
      years presented with well-defined subcutaneous nodules in the left
      supraclavicular region and on top of the head, respectively. FNA showed fragments
      of mature fat tissue and numerous dispersed, large, hyperchromatic, often bizarre
      nuclei. Lipoma with atypical cells was diagnosed cytologically in one case and
      atypical lipoma in the other. Histologically both cases were evaluated as
      atypical lipoma. CONCLUSION: A correct cytologic diagnosis of atypical lipoma can
      be established if cytomorphologic features are coupled with clinical data.

PMID- 9167724
TI  - Combined hepatocellular-cholangiocarcinoma. Cytologic findings in four cases.
AB  - BACKGROUND: Rarely do primary hepatic tumors show mixed hepatocellular carcinoma
      (HCC) and cholangiocarcinoma differentiation. Histologic criteria for these
      combined hepatocellular-cholangiocarcinomas (CHCC-C) are not universally agreed
      upon. Cytologic descriptions of CHCC-C are scarce, yet recognition of this tumor
      type may have some prognostic significance. CASES: The clinical and
      cytohistologic findings, including histochemical and immunohistochemical studies,
      in four cases of CHCC-C were reviewed. The specimens consisted of three needle
      biopsies of the liver and one bile duct brushing specimen. In all cases the
      diagnosis of CHCC-C was confirmed by histologic, histochemical and
      immunohistochemical study. CONCLUSION: The reliable diagnosis of CHCC-C on
      cytologic preparations alone is fraught with difficulty. However, the addition of
      cell block or core biopsy histologic material, which may serve as a substrate for
      histochemical and immunohistochemical studies, may permit the diagnosis to be
      made. Serum markers of HCC, when elevated, may raise the suspicion of
      hepatocellular differentiation even when it is not suspected based on examination
      of the cytologic and/or histologic biopsy specimen.

PMID- 9167725
TI  - Chordoma metastatic to the breast diagnosed by fine needle aspiration. A case
      report.
AB  - BACKGROUND: Metastatic breast tumors are rare but need differentiation from
      primary malignant and even benign tumors of the breast to ensure appropriate
      treatment. CASE: A 51-year-old female with chordoma developed a lump in the
      breast 3.5 years after the primary diagnosis. Fine needle aspiration of the lump
      showed classic physaliferous cells with a bubbly appearance and anaplastic cells
      in a magenta, fibrillary background. CONCLUSION: The presence of classic
      physaliferous cells on fine needle aspiration is diagnostic of chordoma, even in
      metastatic lesions.

PMID- 9167726
TI  - Intraoperative squash and touch cytology of chondroid chordoma of the skull base.
      Report of a case with immunocytochemical and immunohistochemical studies.
AB  - BACKGROUND: Chondroid chordoma is a rare variant of chordoma and is usually
      located in the sphenooccipital region. This tumor shows clinical and histologic
      features common to both conventional chordoma and low grade chondrosarcoma and
      has a better prognosis than either of those lesions. To our knowledge, there has
      been no English language report describing its cytologic features. CASE: The
      cytologic features of skull base chondroid chordoma observed in intraoperative
      crush and touch preparations from a 33-year-old female are reported. Touch
      cytology revealed round or stellate cells distributed in a mucoid background
      without a typical epithelial cordlike arrangement. The cells had variably
      vacuolated cytoplasm and round or oval nuclei and showed slight cellular
      pleomorphism. May-Giemsa staining was superior to Papanicolaou staining in
      demonstrating the mucoid matrix and vacuolated cytoplasm of the tumor cells.
      Additionally, crush preparations were effective in demonstrating well
      differentiated chondroid elements. Immunocytochemistry with positivity for S-100
      protein and cytokeratins was an essential adjunct in the cytologic diagnosis of
      chordoma and helped in distinguishing it from other chondrogenic tumors.
      CONCLUSION: It is possible and advantageous to diagnose chondroid chordoma with a
      combination of cytologic and immunocytochemical studies of intraoperative crush
      and touch preparations in conjunction with clinical and radiographic information.

PMID- 9167728
TI  - Proposed guidelines for primary screening instruments for gynecologic cytology.
      Developed by the Intersociety Working Group for Cytology Technologies.

PMID- 9167727
TI  - Primary malignant fibrous histiocytoma of the lung. Report of a case with
      bronchial brushing cytologic features.
AB  - BACKGROUND: Malignant fibrous histiocytoma (MFH) arising primarily in the lungs
      is rare, and a preoperative diagnosis, as well as a surgical planning, is very
      important because of the tumor's propensity for vascular invasion and its low
      incidence of lymph node metastasis. The correct preoperative diagnosis of
      thoracic MFH is not easy to establish because the small fragments from needle and
      transbronchial biopsies are often inadequate for a conclusive histologic
      analysis. A preoperative bronchial brushing cytology suggestion of the diagnosis
      of primary MFH of the lungs may be helpful in such cases. CASE: A 37-year-old
      male presented with a large, irregular mass in the inferior and middle lobes on
      chest roentgenography as well as on computed tomography. Two bronchoscopies were
      performed, with the diagnosis of undifferentiated large cell carcinoma. After
      surgical resection a more sophisticated pathologic analysis, including
      immunohistochemical and ultrastructural studies, revealed a primary MFH of the
      lungs. Revision of the bronchial brushing cytology disclosed many spindle-shaped
      cells with a "comet" configuration, strongly suggestive of MFH. CONCLUSION: The
      bronchial brushing cytology features of spindle-shaped and bizarre,
      multinucleated giant cells with a comet appearance may be the key to the
      cytomorphologic diagnosis of MFH.

PMID- 9167729
TI  - Intraoperative cytologic evaluation of pancreatic biopsies.

PMID- 9167730
TI  - Fine needle aspiration cytology of juvenile hypertrophy of the breast.

PMID- 9167731
TI  - Aspiration cytology of glycogen-rich squamous cell carcinoma: significance of a
      tigroid smear background.

PMID- 9167732
TI  - Rapid diagnosis of intrauterine pregnancy by smear cytology.

PMID- 9167733
TI  - Adult filarial worm in a fine needle aspirate of a soft tissue swelling.

PMID- 9167734
TI  - Meningioma: local recurrence and pulmonary metastasis diagnosed by fine needle
      aspiration.

PMID- 9167735
TI  - Aspiration of fetal fluids.

PMID- 9167736
TI  - Fine needle aspiration cytology of clear cell sarcoma of the kidney and its
      distinction from Wilms' tumor.

PMID- 9167737
TI  - Potential pitfalls in the diagnosis of Castleman's disease of the mediastinum on
      fine needle aspiration biopsy.

PMID- 9167738
TI  - Cytopathology of granulocyte colony-stimulating factor-producing lung
      adenocarcinoma.

PMID- 9167739
TI  - Microfilaria in a fine needle aspirate from the salivary gland.

PMID- 9167740
TI  - Adjuvant chemotherapy with doxorubicin-containing regimen for 326 stage II breast
      cancers: 15-year results.
AB  - Between 1975 and 1986, 326 patients with stage II breast cancer were treated with
      an adjuvant combination of doxorubicin, vincristine, cyclophosphamide, and 5
      fluorouracil (AVCF) following regional therapy (232 modified radical mastectomy,
      94 lumpectomies, 304 irradiations). The AVCF regimen consisted of 4-week cycles
      of doxorubicin (30 mg/m2 day 1, modified radical mastectomy), vincristine (1
      mg/m2 day 2), 5-fluorouracil 400 (mg/m2), and cyclophosphamide (300 mg/m2) days 3
      6. Two hundred twenty-four patients (pts) had six cycles and 102 pts 12 cycles;
      90 pts also received 30 mg daily tamoxifen for 1 year after chemotherapy. As of
      March 1994, the median follow-up was 130 months (range 86-221). One hundred
      eighteen pts developed recurrences (7 local, 19 controlateral, 92 metastatic) and
      104 died. Estimated disease-free survival (DFS) was 5 years, 76 +/- 5%; 10 years,
      64 +/- 5%; 15 years, 54 +/- 9%. Overall survival (OS) was 5 years, 85 +/- 4%; 10
      years, 70 +/- 5%; 15 years, 58 +/- 10%. Survival was affected by the number of
      involved lymph nodes (258 pts were N+), menopausal status (OS at 15 years: 53%
      for MP+ and 65% for MP-) and Scarff-Bloom-Richardson grading, but not by hormonal
      receptors, number of courses, or associated hormonotherapy. Minimal cardiac
      toxicity was induced by doxorubicin either during or subsequent to treatment
      completion.

PMID- 9167741
TI  - Fractionated stereotactic radiotherapy with cis-platinum radiosensitization in
      the treatment of recurrent, progressive, or persistent malignant astrocytoma.
AB  - External beam irradiation of malignant astrocytoma often provides temporary local
      tumor control, but dose is limited by potential toxicity to normal brain.
      Fractionated stereotactic radiotherapy (SRT) provides additional radiation to the
      tumor with less dose deposition in adjacent normal brain. We administered a
      potential radiosensitizer, cis-platinum (CDDP), to optimize the therapeutic
      index. CDDP (40 mg/m2) was given weekly, with SRT once or twice weekly, to 20
      patients. One had a partial response, 11 stable disease, and eight progressed
      despite therapy. Acute toxicities were manageable. Five patients required surgery
      for tumor progression or radiation necrosis. Median response duration was 18.5
      weeks and median survival was 55 weeks. SRT combined with CDDP is safe, with
      durable responses in some patients. Further investigations to determine optimal
      SRT and CDDP doses and scheduling are justified.

PMID- 9167742
TI  - Paclitaxel as salvage therapy in advanced pretreated ovarian cancer: a phase II
      study.
AB  - The response rate to salvage chemotherapy in advanced ovarian cancer has been
      disappointing in patients who do not respond or who relapse after platinum
      containing regimens. In these cases, the identification of new drugs is a
      substantial challenge. The efficacy of one of these, paclitaxel, has already been
      assessed in many phase II trials. From July 1993 to October 1995, 33 patients
      with advanced ovarian cancer, recurrent or refractory after platinum-based
      regimens, entered our study. Paclitaxel was given by 3-hour intravenous infusion
      every 3 weeks. All the patients were evaluable for toxicity and 27 for response.
      Nine patients (33.3%) responded: 6 complete (22.2%) and 3 partial responses
      (11.1%). Six responses (35.3%) were observed in the 17 platinum-resistant
      patients and 3 (30%) in the 10 platinum-responders. World Health Organization
      (WHO) grade 3-4 neutropenia was common (13/33 patients, 39.4%) and peripheral
      neurotoxicity was observed in 29 patients (87.8%), but was WHO grade 3 in four
      cases (12.1%). Alopecia was ubiquitous, whereas other toxic effects were not
      significant. The overall response rate to paclitaxel in this study is similar to
      that reported in others and the high complete response (CR) rate should be
      emphasized. These data confirm the significant activity and safety of this drug
      in patients with advanced ovarian cancer, even in platinum-resistant cases.

PMID- 9167743
TI  - Paclitaxel as a radiosensitizer combined with fractionated stereotactic
      radiotherapy in the treatment of recurrent medulloblastoma.
AB  - This report describes the treatment of a 39-year-old man with recurrent
      medulloblastoma previously treated with extensive chemotherapy and radiation
      therapy. A novel treatment technique combining paclitaxel (275 mg IV bolus) and
      fractionated stereotactic radiotherapy (30 Gy in six fractions over 3 weeks) was
      given to palliate the patient's significant neurologic symptoms. The patient
      experienced a significant improvement both radiographically and in the quality of
      his life at follow-up 5 months after completion of treatment. No toxicity has
      been observed. The treatment of medulloblastoma with paclitaxel and fractionated
      stereotactic radiotherapy, either alone or in combination, merits further
      investigation.

PMID- 9167744
TI  - Effect of angiotensin II on arteriovenous shunting assessed by hepatic arterial
      perfusion scintigraphy.
AB  - Angiotensin II (AT II) has been reported to improve drug delivery in
      intraarterial chemotherapy for hepatic tumors. We studied the effect of this
      agent on arteriovenous (AV) shunting in the liver. Eleven patients with hepatic
      tumors and an indwelling catheter in the hepatic artery underwent hepatic
      arterial perfusion scintigraphy with and without AT II infusion. At baseline,
      following the administration of technetium-99m macroaggregated albumin (Tc-99m
      MAA) through the catheter, static images of the upper abdomen and whole-body
      anterior and posterior images were obtained. Two to 14 days later, AT II was
      infused via the catheter one minute prior to Tc-99m MAA injection, and imaging
      was performed in the same way as the baseline study. Visual interpretation of the
      static images showed improvement of drug delivery to the hepatic tumors in eight
      of 11 patients and no changes in the remaining patients. The percent injected
      dose in the lungs assessed quantitatively using the whole-body images increased
      in all patients, suggesting enhancement of AV shunt flow. It was concluded that
      intraarterial infusion of AT II increases AV shunting in the liver with better
      targeting to hepatic tumors.

PMID- 9167745
TI  - A phase II study of 5-fluorouracil, leucovorin, adriamycin, and cisplatin (FLAP)
      for metastatic gastric and gastroesophageal junction adenocarcinoma. A Penn
      Cancer Clinical Trial Group and Roswell Park Cancer Institute Community Oncology
      Research Program Trial.
AB  - A Phase II study was performed to evaluate the activity and toxicity of 5
      fluorouracil, leucovorin, Adriamycin, and cisplatin combination chemotherapy
      (FLAP) in patients with previously untreated advanced gastric and
      gastroesophageal (GE) junction adenocarcinoma. Forty-two consecutive patients
      were enrolled to received FLAP in this multi-institutional trial. Response,
      toxicity, and survival data were noted. Fifteen of 42 (36%) patients demonstrated
      objective responses, with two complete responses (5%) and 13 partial responses
      (31%). The median time to disease progression was 17 weeks, and the overall
      survival duration was 30 weeks. Myelosuppression was significant, requiring dose
      modifications, but there were no treatment-related deaths. FLAP is an active
      regimen in the treatment of advanced gastric and GE junction adenocarcinoma. We
      are presently using this regimen in the neoadjuvant setting in patients with
      gastric and GE junction cancers.

PMID- 9167746
TI  - Tumor markers in the diagnosis of malignant serous effusions.
AB  - To assess the possibility of increasing the detection rates of cytological
      examination in malignant effusions by the selection of specific tumor markers for
      a given type of tumor, we measured CEA, CA 19.9, CA 15.3, MCA, PSA, and AFP in
      malignant effusions from 89 patients with the following primary malignancies:
      colon, stomach, breast, liver, prostate, lung, and kidney. Cytological
      examination was positive in only 35 of 89 patients (40%), while the tumor markers
      were positive in 72 of 89 cases (80%). However, apart from small cell lung and
      kidney cancers, where the lack of a specific tumor marker resulted in no
      advantage, in the other types of tumors, the specific marker for each tumor
      identified correctly malignant effusions in 72 of 74 cases (97%). In fact, CEA
      was positive in 11 of 11 effusions induced by colorectal cancer; CA 19.9 in 28 of
      30 gastric cancer effusions, while MCA and CA 15.3 were positive in breast cancer
      effusions (16/22 and 20/22). Finally, elevated AFP and PSA indicated
      hepatocellular and prostate cancer, respectively. In conclusion, in cancer
      patients with elevated effusion levels of specific tumor markers, the effusions
      could be considered of a malignant nature even without cytologically demonstrable
      tumor cells.

PMID- 9167747
TI  - A phase II trial of edatrexate in patients with advanced renal cell carcinoma. An
      Eastern Cooperative Oncology Group study.
AB  - We performed a Phase II trial of edatrexate in 44 chemotherapy-naive patients
      with advanced renal cell carcinoma. Prior therapy with one biological-response
      modifier was permitted. Most patients had multiple sites of metastatic disease
      and were considered to have a poor prognosis using Eastern Cooperative Oncology
      Group criteria. Edatrexate was administered intravenously at a dose of 80 mg/m2
      weekly with 5 weeks of therapy considered one cycle. Oral cryotherapy using ice
      chips was administered before each edatrexate dose. Thirty-seven patients were
      eligible and evaluable for toxicity and response. Two patients obtained a partial
      response, for an overall response rate of 5.4% (95% confidence interval of 0.6%,
      18.2%); one patient remained in remission at 26+ months. Three treatment-related
      deaths occurred. Toxicity was severe, with stomatitis, myelosuppression, and
      other gastrointestinal side effects most prominent. Edatrexate in this dose and
      schedule has minimal activity in advanced renal cell carcinoma and is toxic.

PMID- 9167748
TI  - High dose rate vaginal brachytherapy in early stage endometrial carcinoma:
      preliminary analysis.
AB  - From 1987 to 1993, 69 women diagnosed with FIGO stages I and II carcinoma of the
      endometrium underwent postoperative adjuvant irradiation (RT) under protocol with
      high dose rate (HDR) afterloading vaginal apex brachytherapy. All patients
      initially underwent total abdominal hysterectomy and bilateral salpingo
      oopherectomy. Forty-four women received HDR brachytherapy alone and 25 received
      external beam RT as well as HDR brachytherapy. The median follow-up was 45
      months. The 5-year disease-free survival was 92% and the overall survival rate
      was 79%. Multivariate Cox regression analysis revealed that grade, age, and stage
      were significant predictors of survival. The overall acute and late side effects
      were minimal. It appears that HDR vaginal brachytherapy is prevention of vaginal
      recurrence in endometrial carcinoma and should be considered an effective
      treatment option.

PMID- 9167749
TI  - Phase I dose intensification study of 2-weekly epirubicin with GM-CSF in advanced
      cancer.
AB  - This study investigated dose intensification of epirubicin administered as a 2
      weekly regimen with granulocyte-macrophage colony-stimulating factor (GM-CSF)
      support. The aim was to define the maximally tolerated dose of epirubicin and to
      assess the efficacy of GM-CSF to ameliorate its toxicity. Patients with
      anthracycline-responsive advanced malignancies were eligible. Six dose levels,
      commencing at 90 mg/m2, of epirubicin administered every 2 weeks for four courses
      were planned with GM-CSF 10 micrograms/kg/day administered for 10 days from the
      second day of each course. Six patients were to be entered at each dose level,
      and escalation to the next level was based upon toxicity criteria. Twelve
      patients were entered, six at dose level 1 (90 mg/m2) and six at dose level 2
      (120 mg/m2). Prospectively defined haematological dose-limiting toxicities were
      noted in one patient at dose level 1 and in five patients at dose level 2.
      Further dose escalation was not attempted. Significant nonhaematological
      toxicities included febrile neutropenia in two and four patients at dose levels 1
      and 2, respectively. This study has demonstrated that epirubicin can be safely
      administered at 2 week intervals with GM-CSF at a dose of 90 mg/m2, equivalent to
      the previously reported maximum tolerated dose intensity of 45 mg/m2/week.
      Neutropenia was dose-limiting despite the use of GM-CSF.

PMID- 9167750
TI  - Effect of brain irradiation on blood-CSF barrier permeability of chemotherapeutic
      agents.
AB  - Effect of irradiation on blood-cerebrospinal fluid (CSF) barrier (BCB) was
      studied quantitatively by observing the effect of methotrexate (MTX) permeation
      into the CSF before, during, and after brain irradiation after i.v. injection of
      MTX. Observation of 15 brain tumor patients indicated that in large brain tumors,
      the BCB was seriously damaged; in small tumors, the BCB would gradually open.
      Compared with the findings before irradiation, the increase of permeability of
      MTX was zero to threefold. It is thus advisable to give chemotherapy only after
      20 Gy of irradiation.

PMID- 9167751
TI  - Standard-dose recombinant human granulocyte colony-stimulating factor (rhG-CSF)
      allows safe and repeated administration of high-dose cyclophosphamide, etoposide,
      and cisplatin (CEP).
AB  - High-dose chemotherapy often requires hematopoietic progenitor cell reinfusion,
      but drugs with extramedullary dose-limiting toxicity may be administered in the
      high-dose range by simple growth factor support. In this study, we evaluated the
      feasibility and toxicity of a three-drug high-dose regimen supported by
      recombinant human granulocyte colony-stimulating factor (rhG-CSF). Ten patients
      with histologically proven malignancy were enrolled. Eight had breast cancer, one
      non-Hodgkin's lymphoma, and one a mediastinal tumor of unknown origin. The
      regimen included cyclophosphamide (C) 5 g/m2, etoposide (E) 1.5 g/m2, and
      cisplatin (P) 150 mg/m2 (CEP), administered in a 3-day schedule followed by rhG
      CSF, 300 micrograms once a day, beginning from day +5 (36 h after the end of
      chemotherapy). The cycle was repeated as clinically needed up to three times.
      After the first course, hematologic recovery was rapid and complete without
      documented infections, and no relevant extramyeloid toxicities were observed.
      Eight of 10 patients received a second course with comparably low toxicity, and
      three of them received a third course. We concluded that CEP therapy can be
      administered safely and even repeatedly, by simple growth factor support, in good
      performance status cancer patients.

PMID- 9167752
TI  - Primary non-Hodgkin's lymphoma of the maxillary sinus.
AB  - Primary non-Hodgkin's lymphoma of the maxillary sinus is a rare lesion. We
      studied nine patients with malignant lymphoma involving the maxillary sinus,
      treated between 1980 and 1994 in the Kyushu University Hospital. All lymphomas
      had a diffuse pattern; five were the large-cell type, two the mixed type, and one
      the small lymphatic and small cleaved type. Immunohistologically, all tumors were
      B-cell type. Using the Ann Arbor staging system, six patients were classified as
      stage I, two stage II, and one stage IV. Two patients received only radiotherapy
      because of advanced age; the remaining seven received a combination of
      radiotherapy and chemotherapy (CHOP or VEPA). The tumor doses ranged from 30 to
      51 Gy (mean, 46.7). The mean follow-up was 51 months. Only one patient (stage IV)
      died of disease, and eight stage I-II patients were rendered disease-free. The 5
      year survival rate was 80%, suggesting that primary lymphoma of the maxillary
      sinus has a relatively good prognosis.

PMID- 9167753
TI  - Cisplatin, mitomycin, and vindesine followed by intraoperative and postoperative
      radiotherapy for stage III non-small cell lung cancer: final results of a phase
      II study.
AB  - Sixty-two patients with stage III non-small cell lung cancer (NSCLC) were treated
      with neoadjuvant chemotherapy consisting of cisplatin 120 mg/m2 day 1, mitomycin
      8 mg/m2 day 1, and vindesine 3 mg/m2 days 1 and 14. Each cycle was repeated every
      4 weeks for a total of 1 to 6 cycles (median, 3 cycles). Resection was attempted
      4 to 5 weeks after the last course of chemotherapy. Intraoperative radiation
      therapy (IORT) (10-15 Gy) was delivered during surgery and postoperative external
      beam radiotherapy (EBRT) (46 Gy) was begun 4 weeks after surgery. Fifty-five
      patients (25 IIIA, 30 IIIB) were evaluable. Only partial responses occurred
      (64%), and 29 patients (53%) underwent resection. Complete resection rates were
      85% (12/14) and 40% (6/15) in stage IIIA and IIIB, respectively (p = 0.01). In 3
      of 29 patients (10%), no tumor was found in the resected specimen. There was one
      chemotherapy-related death and three postoperative-related deaths. The median
      survival time was 10 months, and the 5-year survival rate was 29 and 7% for stage
      IIIA and stage IIIB, respectively (p = 0.3). High complete resection rates and
      modest increase in 5-year survival have been observed in stage IIIA NSCLC.
      Although a number of stage IIIB patients can be made technically resectable, the
      low complete resectability rate reflects the lack of survival benefit in these
      patients.

PMID- 9167755
TI  - Pretreatment characteristics of carcinoid tumors of the lung which predict
      aggressive behavior.
AB  - Carcinoid tumors of the lung are uncommon and usually have a favorable outcome
      after resection. However, some patients have aggressive tumors that cannot be
      completely resected or have unfavorable outcomes after resection. A retrospective
      study was conducted to identify factors that predict outcome. Records of all
      previously untreated patients treated at the University of Texas M. D. Anderson
      Cancer Center (UTMDACC) between 1959 and 1994, with histologically confirmed
      carcinoid tumors of the lung, were reviewed. Histologic specimens were
      reclassified by contemporary criteria. Five-year survival for 79 patients without
      distant metastasis who had tumors with clinically aggressive features at
      diagnosis (defined as extension to the carina, involvement of regional lymph
      nodes, and/or vascular invasion) was 50.9% as compared with 76.9% (p = 0.01) for
      patients without these features. Five-year survival was 38.7% for patients with
      "atypical" histopathology (p = 0.01). Patients with aggressive tumors were more
      likely to have atypical tumors [odds ratio (OR) 11.73, p < 0.001]. However, 17.5%
      of the patients with clinically aggressive carcinoid tumors had tumors that were
      classified as typical. Carcinoid tumors of the lung that exhibit aggressive
      behavior may not have atypical histopathologic features. Clinical features that
      suggest aggressive behavior and unfavorable outcome warrant further
      investigation.

PMID- 9167754
TI  - Mitomycin lung toxicity. Acute and chronic phases.
AB  - Pulmonary toxicity is a rare but well described side effect of mitomycin C (MMC).
      We describe 14 cases of MMC pulmonary toxicity that were detected in four
      clinical trials performed at The Mayo Clinic using MMC-containing regimens for
      nonsmall cell lung cancer (NSCLC) and by reviewing the charts of patients treated
      at The Mayo Clinic with MMC-containing regimens for NSCLC from 1976 to 1995. The
      median age was 61 (range 44-84) years, with an M:F ratio of 1:1. The median
      number of cycles of MMC to develop toxicity was four (range two to five) with a
      median cumulative dose of MMC of 29 mg/m2. MMC toxicity occurred despite pre
      medication with corticosteroids in 11 patients. At diagnosis of MMC lung
      toxicity, the median diffusing lung capacity (DLCO) was 9 and PaO2 was 49 mm Hg.
      Of those having bronchoscopy, four patients had pulmonary histologic changes
      consistent with lung injury. Two patients had bronchioalveolar lavages that were
      nondiagnostic. All patients responded initially to corticosteroids, but
      approximately 40% had progressive pulmonary insufficiency despite high doses of
      corticosteroids. This chronic, progressive phase of MMC lung toxicity is a
      largely underestimated sequelae of MMC.

PMID- 9167756
TI  - A prospective phase II trial to evaluate the efficacy and toxicity of hepatic
      arterial infusion of ifosfamide in patients with inoperable localized
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a common tumor in the developing countries.
      Most patients present with relatively advanced disease and have a poor survival.
      Due to lack of any effective therapy, there is an urgent need to investigate new
      drugs. We conducted a prospective trial to evaluate the efficacy and tolerability
      of ifosfamide (IFEX) in patients with histologically proved, inoperable,
      localized HCC. Eligibility criteria included World Health Organization (WHO)
      performance status (PS) of 0-2, bilirubin < or = 3.0 mg/dl, albumin > or = 2.5
      g/dl, creatinine < or = 2.0 mg/dl, correctable coagulation profile, adequate bone
      marrow function, and no prior therapy. Hepatic arterial infusion of IFEX (6 g/m2)
      was given continuously over 96 hours. Mesna was given intravenously, in same
      doses, throughout IFEX infusion and for 12 hours afterwards. Nineteen patients
      were enrolled in the trial. Mean age was 51.1 years and all were men. Most of the
      patients had PS 1. The majority had viral hepatitis and cirrhosis. Eleven had
      raised serum alpha fetoprotein (AFP) levels. Thirteen patients had multiple
      lesions involving both lobes of the liver. Mean size of ultrasonographically
      evident largest lesion was 11.0 cm. Three patients are inevaluable; one died
      early, one refused further therapy, and another was lost to follow-up. Among the
      16 evaluable patients, 6 (37.5%) had partial remission and 4 (25%) had a minor
      response. An additional four (25%) patients had stable disease. Only two (12.5%)
      patients had progression of disease while on therapy. Overall response rate
      (partial plus minor) was 62.5%. Mean duration of partial response was 5.0 months
      and mean survival was 7.1 months. Subjective improvement in pain was observed in
      all but two patients and correlated well with the objective response.
      Chemotherapy-related side effects were predominantly grade III-IV anemia and
      alopecia. Three patients had catheter-related complications (one local infection,
      one bleeding, and one thrombosis). Two patients developed mild encephalopathy and
      two had hepatic decompensation as evidenced by worsening liver function tests.
      The results of this pilot study suggest that IFEX, given as a continuous hepatic
      arterial infusion, is an active drug in inoperable localized HCC. Toxicity is
      manageable. This drug deserves further trials to properly evaluate its
      therapeutic potential.

PMID- 9167757
TI  - Treatment of superior and inferior vena cava syndromes of malignant cause with
      Wallstent catheter placed percutaneously.
AB  - Superior vena cava syndrome (SVCS) and inferior vena cava syndrome (IVCS)
      represent a severe symptomatic complication of some malignant tumors. Although
      radiation therapy and chemotherapy are elective, symptomatic relief takes 7-10
      days to be achieved, and poor symptomatic benefit can be obtained in relapsed or
      resistant tumors. We report on a palliative approach using Wallstent catheters
      placed percutaneously in a series of 16 patients. Results obtained in relief of
      symptoms were excellent (complete response of cephalea, jugular enlargement, and
      collateral circulation achieved in 100% [16/16] of patients; complete response of
      edema obtained in 93% [15/16] of patients). Achievement of symptomatic response
      was obtained for all symptoms during the first 24 h poststenting, except for
      edema and dyspnea. Mean duration of patency of the stents was 6.4 months (range 2
      17 months). Rates of morbidity and complications were very low. Dyspnea was a
      quite resistant symptom, and only four of 13 patients (31%) obtained complete
      response, while partial improvement was obtained in the other nine (79%).
      However, placement of the stents does not preclude the use of radiation therapy
      or chemotherapy. We think that these results and those from other studies warrant
      larger multicentric trials.

PMID- 9167758
TI  - A phase II study of topotecan in patients with recurrent head and neck cancer.
      Identification of an active new agent.
AB  - This study evaluated the efficacy and safety of topotecan, a topoisomerase I
      inhibitor, in patients with advanced squamous cell cancer of the head and neck.
      Topotecan was administered intravenously (over 30 min) daily for 5 days every 3
      weeks at a starting dose of 1.5 mg/m2/day. Eligibility required no prior
      chemotherapy, measurable disease, and performance status of < or = 2. Quality of
      life (QOL) assessment was performed at specified time points using the Spitzer
      QOL index and the symptom distress scale. Of 26 patients entered into the study,
      23 and 22 patients were assessable for toxicity and response, respectively. One
      complete and two partial responses were observed, with response durations of 9,
      4, and 1.5 months, respectively. Six patients had stable disease, including one
      patient with a 45% tumor shrinkage. The median survival for all patients entered
      was 4 months. Neutropenia was the major dose-limiting side effect, with grade 4
      toxicity observed in 42% of all cycles of treatment. Grade 3 anemia occurred in
      16% of all cycles, and nine patients required blood transfusions. Nonhematologic
      toxicities were infrequent and mild to moderate. QOL assessment revealed no
      significant change of total scores between each assessment point. Topotecan is a
      well-tolerated new agent with similar single-agent activity to that of cisplatin,
      5-fluorouracil, and methotrexate in advanced head and neck cancer. Further
      investigation of this agent with other chemotherapeutic drugs and with concurrent
      radiation therapy is appropriate.

PMID- 9167759
TI  - Activity of combination chemotherapy in brain metastases from breast and lung
      adenocarcinoma.
AB  - Brain metastases represent a common complication of breast and lung cancer, with
      an overall incidence exceeding 30-40% of cases. Results achieved with
      radiotherapy are disappointing, with a median survival of a few months, and no
      clear activity has been observed with chemotherapy. The aims of this study were
      to assess the activity and feasibility of a new chemotherapeutic approach
      according to the following schedule: lomustine, 80 mg/m2 day 1; carboplatin, 80
      mg/m2 days 1, 8, 15, 22; vinorelbine, 20 mg/m2 days 1, 8, 15, 22; L-leucovorin
      250 mg/m2 days 1, 8, 15, 22; and fluorouracil, 500 mg/m2 days 1, 8, 15, 22.
      Cycles were repeated every 6 weeks. Since January 1994, 28 patients have been
      enrolled and 26 are evaluable for response and side effects. Major patient
      characteristics were median age, 55 years (range 31-72); men/women 15/11; lung
      primary, 20; breast primary, 6; performance status Eastern Cooperative Oncology
      Group, 0-2. A total of 64 cycles were administered (median/patient, two cycles).
      Nine partial remissions have been observed (35%, 95% confidence interval 17-56%),
      6 disease stabilizations, and 11 disease progressions. Median duration of
      response was 3 months, and median time to progression for the whole group was 3.7
      months (range 1-7). Treatment was well tolerated. Mild or moderate side effects
      included neutropenia, thrombocytopenia, mucositis, and nausea/vomiting; grade III
      IV toxicity included neutropenia and thrombocytopenia. In conclusion, our results
      indicate that the schedule proposed is feasible and effective in this subset of
      patients.

PMID- 9167760
TI  - Megestrol acetate in the treatment of hormone refractory prostate cancer.
AB  - This retrospective study evaluates the efficacy of megestrol acetate in patients
      with hormone refractory metastatic adenocarcinoma of the prostate. Data are
      presented from 14 patients with advanced prostatic adenocarcinoma who were
      treated with 160-320 mg of megestrol acetate daily. Each patient was either
      asymptomatic or had minimal cancer-related symptoms. Disease response was
      monitored by prostate-specific antigen levels. The response rate was 14%, with
      two patients having a partial response. No complete responses were observed. The
      median time to disease progression was 2 months. Our findings when considered
      together with results from previously published data demonstrate little activity
      of megestrol acetate in patients with hormone refractory prostate cancer.
      Therefore, we cannot recommend megestrol acetate as an effective second-line
      therapy.

PMID- 9167761
TI  - Evaluation of long-term daily administration of oral low-dose etoposide in
      elderly patients with relapsing or refractory non-Hodgkin's lymphoma.
AB  - Etoposide produces reversible inhibition of topoisomerase II, leading to cleavage
      of DNA, and thereby has an antitumor effect. This mechanism suggests that the
      longer treatment is continued, the greater the antitumor effect will be. In the
      present study, both therapeutic and adverse effects of long-term treatment with
      low-dose oral etoposide were studied in 29 patients aged > or = 65 years with non
      Hodgkin's lymphoma (NHL) for whom standard chemotherapy was not effective or
      refractory. These patients received etoposide at a dose of 50 mg/d for as long as
      possible. Treatment was continued until white blood cell count decreased to < or
      = 2,000/microL or the platelet count decreased to < or = 5 x 10(4)/microL.
      According to the World Health Organization (WHO) criteria of therapeutic effects,
      6 (20.7%) of the 29 patients achieved complete remission and 13 patients (44.8%)
      had partial remission, for a response rate of 65.5%. Adverse effects of > or =
      grade 3 included leukopenia in 24 patients (82.8%) and anemia in 7 (24.1%).
      Granulocyte colony-stimulating factor (G-CSF) was given in combination with
      etoposide to eight patients because of leukopenia (granulocyte count < or =
      1,000/microL). In view of the excellent subjective tolerance, low incidence of
      serious adverse effects, and good activity, single agent oral etoposide given
      continuously over prolonged periods represents a useful treatment for elderly
      patients with NHL.

PMID- 9167762
TI  - The addition of bleomycin and dose-escalated ifosfamide to the combination of
      cisplatin plus ifosfamide does not improve survival in advanced or recurrent
      cervical carcinoma.
AB  - Twenty patients with advanced or recurrent cervical cancer were treated with
      bleomycin 30 U, ifosfamide 5 g/m2, and cisplatin 50 mg/m2 (BIP) every 28 days in
      a phase II trial. The primary purpose of this study was to compare response rate,
      survival, and toxicity of this regimen with results obtained in a similar group
      of patients treated with cisplatin 1 mg/kg per week for six courses followed by
      cisplatin, 20 mg/m2, plus ifosfamide 1.2 g/m2 daily for 3 days every 28 days.
      Four of 17 evaluable patients (23.5%) treated with BIP demonstrated a response to
      therapy (complete response 11.7%; partial response 11.7%). The median duration of
      response was 8.5+ months (range, 6+ to 24 months). These data do not differ
      significantly (P = 0.76) from a response rate of 27.5% among patients treated
      with cisplatin plus ifosfamide (PI). A significant (P = 0.003) increase in
      myelotoxicity was observed among patients treated with BIP versus those treated
      with PI. The median survival of patients treated with BIP of 13.5+ months (range,
      8+ to 24 months) does not differ significantly from the median survival of 9+
      months (3 to 26+ months) among patients treated with PI. The addition of
      bleomycin and dose-escalated ifosfamide did not significantly improve response
      rate or survival among patients with advanced or recurrent cervical cancer and
      resulted in a significant increase in myelotoxicity.

PMID- 9167763
TI  - A phase II trial of cisplatin and interferon alpha 2b in patients with advanced
      bladder cancer.
AB  - Twenty-two patients with advanced transitional cell bladder cancer were treated
      in a phase II trial exploring the possible synergy of cisplatin and interferon
      alpha 2b. Of the 20 evaluable patients, 7 (35%) had a partial response to the
      treatment, and only 6 patients were able to complete the full planned six cycles
      of treatment. Response rates, duration of responses, and overall survival of our
      patients are not superior to those expected by cisplatin alone.

PMID- 9167764
TI  - Rheumatic symptoms following adjuvant therapy for breast cancer.
AB  - Twenty-three women with a diagnosis of breast cancer who subsequently developed
      new nonmetastatic rheumatic symptoms, and/or had a history of rheumatic symptoms
      prior to their diagnosis of breast cancer, were identified from the oncology and
      rheumatology practices of a 400-bed tertiary-care teaching hospital. For each
      patient a structured telephone interview and detailed chart review were
      conducted. Of eight women with no previous rheumatic history (Group I), four
      developed polyarthritis (1 seropositive), three fibromyalgia, and one spondylosis
      after the diagnosis of breast cancer, which in four cases occurred during or
      shortly after cyclophosphamide-based combination chemotherapy, in two cases
      during tamoxifen therapy, and in one case after radiotherapy only. Of 15 women
      who had previous rheumatic symptoms (Group II), 12 developed worse and/or new
      symptoms, five after chemotherapy and seven on tamoxifen. In both groups the
      symptoms had a significant negative impact on functional status, and in some
      cases resolution was only partial even after many years of followup. Prospective
      studies are needed to determine the incidence, risk factors, and optimal
      management of nondestructive polyarthropathy or fibromyalgia in women who receive
      systemic adjuvant therapy for breast cancer.

PMID- 9167765
TI  - Apoptotic program is initiated but not completed in LNCaP cells in response to
      growth in charcoal-stripped media.
AB  - BACKGROUND: Morphological, proliferative, and genetic changes were studied in
      androgen-responsive LNCaP cells in response to growth in charcoal-stripped (CS)
      media. METHODS AND RESULTS: Within 5 days of treatment, there were dramatic
      changes in the morphology and organization of LNCaP cells. The cells unclumped
      and acquired a distinct neuronal-like appearance with small cell bodies and
      multiple long, thin processes. Despite this appearance, the cells stained
      negative to monoclonal antibodies to neuronal markers such as microtubule
      associated protein-2 (MAP-2) and glial fibrillary acidic protein (GFAP). In situ
      end-labeling assay indicated that the number of cells showing signs of apoptosis
      (DNA fragmentation) increased dramatically in CS media compared to the control.
      However, ultrastructural changes and the fragmented DNA ladder that are used to
      define apoptosis were not observed. Instead of cell death, the cells became
      cytostatic, which can be reversed, although not completely, by exogeneous
      addition of dihydrotestosterone in a dose-dependent manner. Presence of mRNA of
      several genes involved in the apoptotic process, i.e., Bcl-2, Bcl-X, ICE, Ich-1,
      and DAD-1, was studied in response to normal and CS media. We detected mRNA of
      Bcl-2, Bcl-XL, Bcl-XS, Ich-1L and DAD-1, while ICE and Ich-1S were not expressed
      in LNCaP cells. CONCLUSIONS: This suggests that certain signals that may be
      essential for complete execution of the apoptotic program may be missing in this
      in vitro model. This may explain our observation that the growth of LNCaP cells
      in CS media does not fully mimic castration-mediated regression of the prostate
      gland in vivo.

PMID- 9167766
TI  - Anemia associated with advanced prostatic adenocarcinoma: effects of recombinant
      human erythropoietin.
AB  - BACKGROUND AND METHODS: Nine patients with hormone-refractory metastatic
      prostatic adenocarcinoma and anemia were treated with recombinant human
      erythropoietin (rHuEpo) at a median dose of 150 U/kg BW 3 times a week
      subcutaneously. Baseline hemoglobin (Hb) ranged from 70 to 116 g/L, and the study
      duration was 12 weeks (median patient participation period was 8 weeks). RESULTS:
      Four patients demonstrated a median Hb increase of 20 g/L and were considered
      responders. Three patients showed a median increase of 17 g/L but required blood
      transfusion once, and were therefore considered as partial responders. Baseline
      erythropoietic status showed a significant correlation between serum Epo and Hb.
      Inadequate Epo production, evaluated by the observed/predicted log Epo ratio, was
      found in two patients. Defective bone marrow activity, demonstrated by low
      transferrin receptor (TfR), and hypoferremia in spite of abundant iron stores
      were also shown. Hemorheological investigations showed elevated plasma viscosity.
      CONCLUSIONS: Our results indicate that suppression of erythropoiesis can be
      mainly explained by the depressed marrow activity. The altered hemorheology might
      contribute to the anemia. This anemia could possibly be corrected with rHuEpo.

PMID- 9167767
TI  - Effect of retinoic acid on prostatic development.
AB  - BACKGROUND AND METHODS: To assess the effect of retinoids on prostatic ductal
      branching morphogenesis, anterior prostates from newborn rats were cultured under
      serum-free conditions for 6 days in the presence of testosterone (10(-8) mM) plus
      13-cis-retinoic acid (13-cis-RA), all-trans-retinoic acid (at-RA), or N-4
      hydroxyphenyl-retinamide (4-HPR). Measures of morphologic complexity were
      computed and compared between specimens of different treatment groups. RESULTS:
      Prostatic ductal growth and branching were inhibited in a dose-dependent fashion
      by both 13-cis-RA and at-RA, but not by 4-HPR. This inhibitory effect of 13-cis
      RA was reversible, as the prostatic ducts resumed branching and growth after
      removal of retinoic acid from the culture medium. Using reverse transcription
      polymerase chain reaction, we then investigated the expression of nuclear
      receptor genes for retinoic acid. CONCLUSIONS: This showed the presence of RAR
      beta and RAR-gamma in the 0-day prostate, suggesting that the effects of these
      retinoids on ductal morphogenesis may be via these receptors.

PMID- 9167768
TI  - Orthotopic implantation of human prostate cancer cell lines: a clinically
      relevant animal model for metastatic prostate cancer.
AB  - BACKGROUND: To study the metastatic behavior of human prostate cancer cell lines,
      orthotopic injection in nude mice was performed. METHODS: Local tumor growth,
      metastasis formation, prostate-specific antigen, and androgen receptor expression
      were examined. RESULTS: Hormone-independent cell lines (PC-3, PC-3-125-IL, and
      TSU-Pr1) were highly tumorigenic and had a higher rate of lymph node metastasis
      after orthotopic than after subcutaneous implantation. PC-3 cell lines also
      consistently metastasized to the lungs. The androgen-sensitive LNCaP cell line
      showed local growth in 7 of 10, and lymph node metastasis in 4 animals.
      Significant serum PSA levels and strong receptor expression in primary and
      metastatic tumor tissues were observed. CONCLUSIONS: These results demonstrates
      that orthotopic implantation of human prostate cancer cell lines, including
      LNCaP, reproducibly leads to metastasis formation in nude mice.

PMID- 9167769
TI  - Histologic differences in benign prostate hyperplasia between Chinese and
      American men.
AB  - BACKGROUND: This investigation sought to determine morphologic differences
      between Chinese and Americans with symptomatic benign prostatic hyperplasia
      (BPH), in an admixture of stroma, epithelium, and luminal spaces. METHODS:
      Adjacent sections of simple prostatectomy specimens from China and the U.S. were
      stained to highlight the stroma and epithelium. Image analysis was performed on
      random fields. RESULTS: Chinese tissue had higher glandular densities (mean =
      12.5 acini/mm2 vs. 6.2 acini/mm2; P < 0.0001), while American samples had higher
      percent stroma (mean = 66% vs. 51%; P = 0.0003). Mean luminal cell heights in the
      Chinese and American prostate acini were 11.7 and 19.0 microns, respectively (P <
      0.0001). CONCLUSIONS: These data indicate significant histologic variation in BPH
      between Chinese and American men undergoing simple prostatectomy. These
      differences may provide a focus for investigating the epidemiological variation
      in clinical BPH and carcinoma between our two countries, and could have
      applications in clinical management of symptomatic BPH.

PMID- 9167770
TI  - Role of finasteride in the treatment of recurrent hematuria secondary to benign
      prostatic hyperplasia.
AB  - OBJECTIVES: We evaluated the efficacy of finasteride for the treatment of gross
      hematuria secondary to benign prostatic hyperplasia in a prospective fashion.
      METHODS: Twelve patients with recurrent episodes of gross hematuria secondary to
      benign prostatic hyperplasia were treated with finasteride 5 mg/day. Before
      initiating treatment, we excluded other sources of hematuria using intravenous
      urography, cystoscopy, and urine culture. RESULTS: Bleeding subsided within 2
      weeks of treatment in all 12 patients. Minimum follow-up was 6 months.
      Finasteride was well tolerated by all 12 patients. CONCLUSIONS: Finasteride
      appears to be effective in treating recurrent gross hematuria secondary to benign
      prostatic hyperplasia. This therapy should be considered an alternative to
      transurethral resection of the prostate or hormonal ablation in patients with
      recurrent hematuria and no significant obstructive uropathy or adenocarcinoma of
      the prostate.

PMID- 9167771
TI  - Neurotensin receptor expression in prostate cancer cell line and growth effect of
      NT at physiological concentrations.
AB  - BACKGROUND: Neurotensin (NT), a neuroendocrine peptide, exerts trophic effects in
      vivo and stimulates growth of some tumor cells in vitro. Androgen-sensitive
      prostate cells derived from lymph node carcinoma of the prostate (LNCaP) secrete
      NT and exhibit growth responses to NT. This study examines NT secretion, NT
      receptor and NT-growth responses in androgen-independent prostatic carcinoma
      (PC3) cells derived from prostate adenocarcinoma metastatic to bone. METHODS:
      Binding of 125I-NT to PC3 membranes was studied by filtration. NT was measured by
      RIA. Reverse transcriptase polymerase chain reaction (RT-PCR) was used for NT and
      NT receptor mRNA. Growth was measured as 3H-thymidine incorporation into DNA.
      RESULTS: Scatchard analyses gave two binding components (Kd1 = 40 pM and Kd2 =
      300 pM) in equal amounts (15-30 x 10(3) sites/cell). The bioactive region of NT
      was essential and the specific, non-peptide NT antagonist, SR48692, inhibited
      (IC50 = 3 nM). GTP analogs, sodium ion and SH-directed alkylating agents also
      inhibited. Glutaraldehyde crosslinking labeled two substances (M(r) of 23 and 46
      kDa). RT-PCR indicated robust expression of authentic NT receptor but little for
      NT precursor. NT was stable in PC3 cultures but it was not found in cells or
      conditioned media. Incubated with PC3 cells, NT exhibited a mitogenic effect with
      bell-shaped dose-response and maximum at 100 pM NT. CONCLUSIONS: PC3 cells
      expressed genuine NT receptors and generated growth responses to physiologic
      levels of NT which were blocked by SR48692. If NT contributes to the survival of
      prostate tumor cells upon androgen deprivation therapy, NT antagonists might be
      useful agents in further treatment.

PMID- 9167774
TI  - Current status of enhancing the detection of prostate cancer.

PMID- 9167772
TI  - Possible bone-preserving capacity of high-dose intramuscular depot estrogen as
      compared to orchidectomy in the treatment of patients with prostatic carcinoma.
AB  - BACKGROUND: Treatment of prostatic disease with GnRH agonists or by orchidectomy
      affects bone mass negatively. Estrogen treatment has beneficial effects on bone
      mass in women and might hypothetically have a bone preserving capacity also in
      patients with prostatic cancer. METHODS: We followed serum markers for bone and
      collagen metabolism and sex steroids for 18 months in patients with prostatic
      cancer treated by orchidectomy (N = 13) or by single-drug parenteral
      polyestradiol phosphate (240 mg intramuscularly every second week for the first
      two months, and then every fourth week; N = 17). RESULTS: Total and free
      testosterone reached castration levels within 1.5 months of estrogen treatment.
      Four patients developing progressive disease and/or signs of metastasis were
      excluded from the analysis. In the remaining patients, serum osteocalcin,
      procollagen IIIP (PIIINP), procollagen (PICP), and the crosslinked
      carboxyterminal telopeptide of type I collagen (ICTP) increased significantly
      over time following orchidectomy (N = 11). Serum osteocalcin and PICP decreased
      significantly over time during estrogen treatment (N = 15). Treatment values of
      all four markers were significantly lower in estrogen-treated than in
      orchidectomized patients. CONCLUSIONS: The changes in serum bone and collagen
      markers indicate an increased bone turnover in orchidectomized subjects. The
      opposite pattern was found in the estrogen-treated patients, indicating a reduced
      turnover. Estrogens may also have a bone mass-preserving capacity in elderly
      males with prostatic cancer.

PMID- 9167773
TI  - Use of a hormone-sensitive (LNCaP) and a hormone-resistant (LNCaP-r) cell line in
      prostate cancer research.
AB  - BACKGROUND: In order to develop a hormone-resistant analog to the hormone
      sensitive cell-line LNCaP, different methods were tried. METHODS: After almost
      one year of continuous culture in RPMI-1640, containing a low concentration of
      androgens, the hormone sensitive cell-line LNCaP became hormone resistant and was
      named LNCaP-r. RESULTS: We used the LNCaP/LNCaP-r model system in order to study
      methods for the parenteral treatment of prostate carcinoma with estrogens, to
      study the mechanism of action of estramustine, and to identify markers useful as
      predictive tests for prostate carcinoma. CONCLUSIONS: A model system made up of
      the hormone sensitive prostate LNCaP cell-line and the hormone resistant LNCaP-r
      subline was developed and characterized. This system is, despite a number of
      limitations, easy to use as a first step to test different hypotheses that can be
      studied further in later clinical trials.

PMID- 9167775
TI  - Importance of management of unruptured cerebral aneurysms.
AB  - BACKGROUND: Since excellent recovery is hardly expected in patients with severe
      subarachnoid hemorrhage, management of unruptured aneurysms is essential in
      reducing the overall mortality and morbidity rates. The widespread use of less
      invasive imaging tools such as magnetic resonance angiography (MRA) has made
      "Brain Check-up Systems" very popular in Japan. Therefore, unruptured aneurysms
      have been found much more often than before. METHODS: During the 1-year period of
      1994, 80 patients underwent radical surgery for aneurysms in our institute.
      Thirty-two patients (40%) underwent surgery for unruptured aneurysms, while 48
      patients (60%) underwent surgery for ruptured aneurysms. In patients with
      unruptured aneurysms, we have operated when the aneurysm is larger than
      approximately 5 mm in diameter, arising from the common sites in the circle of
      Willis, and when the patient's age is under 70 years. To prevent surgical
      complications in unruptured aneurysms, we often use a wrapping technique with
      Bemsheets (cotton) and adhesives. RESULTS: The outcomes were good in all 32 cases
      of unruptured aneurysms. CONCLUSIONS: We believe that early detection and
      prophylactic surgery for unruptured aneurysms will improve the overall outcome of
      aneurysm treatment in the future.

PMID- 9167776
TI  - Transient enlargement of an intracranial aneurysm during pregnancy: case report.
AB  - BACKGROUND: The association of intracranial aneurysm and pregnancy is uncommon.
      Hemodynamic stress plays an important role in the growth of aneurysms. METHODS:
      The authors report the case of an enlarging cavernous carotid aneurysm in a
      pregnant 15-year-old young woman. RESULTS: The aneurysm was initially diagnosed
      prior to the patient's pregnancy by both cross-sectional imaging and cerebral
      angiography. Further imaging evaluation was required during pregnancy, which
      demonstrated significant enlargement of the aneurysm. Following delivery, the
      lesion decreased in size. CONCLUSIONS: We review potential factors associated
      with pregnancy that may increase hemodynamic stress and influence aneurysm
      growth. Additionally, the management of pregnancy-related intracranial aneurysms
      is discussed.

PMID- 9167777
TI  - Concurrent aneurysm rupture and thrombosis of high grade internal carotid artery
      stenosis: report of two cases.
AB  - BACKGROUND: The simultaneous presentation of aneurysmal subarachnoid hemorrhage
      and thrombosis of a high-grade internal carotid artery stenosis is rare, and
      their management raises several treatment dilemmas. METHODS: Two such patients
      with ruptured aneurysms are presented: one with high-grade internal carotid
      artery stenosis that progressed to occlusion and one with acute internal carotid
      artery occlusion. RESULTS: Both patients were treated with craniotomy for
      clipping of the ruptured aneurysm followed by carotid thromboendarterectomy.
      CONCLUSIONS: We advocate urgent surgical treatment of both lesions, dealing with
      the most symptomatic lesion first. These two cases demonstrate the importance of
      reestablishing blood flow in patients with an acutely thrombosed carotid artery.

PMID- 9167778
TI  - Normalization of transcranial Doppler middle cerebral artery velocities after
      aneurysm clipping.
AB  - BACKGROUND: Factors that promote normalization of middle cerebral artery (MCA)
      velocities after cerebral aneurysm surgery may be important to identify in order
      to optimize management. Survival analysis of serial transcranial Doppler (TCD)
      MCA velocities in the setting of aneurysm surgery offers an additional means of
      analyzing outcome. METHODS: We retrospectively studied serial MCA velocities
      obtained via TCD in 113 patients who underwent cerebral aneurysm clipping to
      analyze which factors promoted normalization. The presence of bleeding, aneurysm
      location, age, gender, ethnicity, initial blood pressure, hemoglobin, and
      clinical condition were examined. RESULTS: Patients who did not bleed but were
      clipped still tended to have transient periods of abnormally elevated velocities.
      Of those patients who bled and were clipped, older patients normalized faster.
      Women showed a trend toward slower normalization only in the subarachnoid
      hemorrhage (SAH) absent group. Other parameters listed above did not effect
      normalization time. CONCLUSIONS: Our data suggest aneurysm surgery in and of
      itself may promote transient rises in MCA velocities. Age appears to be a
      significant factor in predicting normalization of MCA velocities after SAH.

PMID- 9167779
TI  - Magnetic characteristics of Yasargil aneurysm clips.
AB  - BACKGROUND: Metallic bioimplants are subject to great scrutiny in order to ensure
      that they are totally harmless to patients. Aneurysm clips are no exception to
      this rule. Considering the number of aneurysm clips used and their potential for
      injury, they should be evaluated very meticulously. Determining the magnetic
      characteristics of these clips is an important part of the evaluation process. In
      this study, a new method for evaluating magnetism is described and the importance
      of that information is briefly discussed. METHODS: Twenty Yasargil aneurysm clips
      were analyzed using a vibrating sample magnetometer under 1.5 Tesla. This device
      is highly sensitive, and is capable of measuring the magnetism of small objects.
      RESULTS: Our measurements showed magnetism of the aneurysm clips ranged from
      0.0334-0.1369 electromagnetic units (emu). CONCLUSIONS: Magnetometer measurements
      and real life tests under magnetic resonance imaging (MRI) have shown that these
      clips have a very low magnetism and are safe to use in 1.5 Tesla MRI scanners.
      This study also proves that the vibrating sample magnetometer is a useful device
      for analyzing the magnetism of aneurysm clips, and their emu values can be used
      as another industry standard in the production line to increase the safety of
      these clips.

PMID- 9167780
TI  - Surgical management of nontuberculous thoracic and lumbar vertebral
      osteomyelitis: report of 33 cases.
AB  - BACKGROUND: Thirty-three patients with nontuberculous pyogenic thoracic and
      lumbar vertebral osteomyelitis were treated surgically. Indications for surgery
      were either progression of disease despite adequate antibiotic therapy,
      neurologic deficit, or both. The most common initial symptom was back pain. Seven
      patients had diabetes, seven patients were intravenous drug users, two patients
      were receiving immunosuppressive therapy, and seven patients had a debilitating
      disease. Eleven had infections elsewhere in their bodies. Prior to surgery
      organisms were grown from blood in 10 patients and at surgery in 15 patients.
      METHODS: Infection was evident on plain films in all patients, and either a CT
      scan or MRI was obtained in each. The lateral extracavitary approach was used for
      resection of granulation tissue and infected bone ventral to the dura. Interbody
      bone grafts were placed in 19 patients, usually when bone resection was
      extensive. Posterior instrumentation was placed in 17 patients at a second
      procedure 10 days-2 weeks following initial operation. Intravenous antibiotics
      were administered for 4-6 weeks following surgery, and solid fusion was obtained
      in all patients. RESULTS: Neurologic deficit was present in 28 patients prior to
      surgery and was functionally significant in 18 patients. Of the 11 patients with
      severe paraparesis, 10 achieved good functional recovery. These patients were
      able to walk, three with assistance and seven without, and all those who were
      unable to void regained this ability. CONCLUSIONS: Surgical debridement,
      interbody fusion, and posterior instrumentation is a safe and effective treatment
      for vertebral osteomyelitis and is indicated when neurologic deficit or bone
      destruction progress despite adequate antibiotic therapy.

PMID- 9167781
TI  - Reoperation for recurrent trigeminal neuralgia after microvascular decompression.
AB  - BACKGROUND: Microvascular decompression (MVD) is an effective technique for those
      who have trigeminal neuralgia (TN) but cannot tolerate, or show no response to
      medicine. Though the initial success rate is high, some patients may develop
      severe recurrent neuralgia, especially after a longer period of follow-up. The
      efficacy of reoperation needs to be evaluated. To know the possible risk factors
      of recurrence after initial MVD is mandatory to the management of recurrent TN.
      METHODS: Among the 80 cases of TN treated with MVD, five cases showed severe
      recurrent symptoms within a follow-up period from 9 months-4 years. The symptoms
      recurred on the same side of the face, and were unresponsive to medical
      treatment. Brain computed tomography (CT) and magnetic resonance imaging (MRI)
      may reveal the etiology of recurrence. Repeat decompression of the trigeminal
      nerve was the main goal of reoperation, which was done via a suboccipital
      approach. RESULTS: Over the past 17 years, 80 MVDs for TN have been performed at
      Chang Gung Memorial Hospital. There were five cases of serious postoperative
      recurrence, which could not be relieved by medicine. Recurrence occurred 1 day-12
      months after the initial surgery. Three cases were due to vascular compression,
      while two were caused by the local effect of Teflon felt. Reoperation produced
      complete remission in four patients, and partial remission in one. CONCLUSIONS:
      An increasing number of patients may experience severe recurrent TN after initial
      MVD during a long period of follow-up. Reoperation is safe and beneficial for
      these patients, but the results are dependent on the etiology of the recurrence.
      Further vascular compression of the trigeminal nerve can be relieved by MVD.
      Otherwise, in cases of severe adhesion caused by Teflon, complete microneural
      lysis can achieve satisfactory results.

PMID- 9167782
TI  - Recurrence of medulloblastoma: violation of Collins' law after two decades.
AB  - BACKGROUND: Medulloblastoma is a common tumor of childhood arising in the
      posterior fossa. The concept of a child with an embryonal tumor surviving the age
      of diagnosis plus 9 months as the period of risk for recurrence (Collins' Law)
      has been applied to medulloblastomas. This raises the question of "when should
      follow-up stop for a patient with this type of tumor?" METHODS: We present a case
      report of a patient with the longest documented exception to Collins' Law for
      medulloblastoma. RESULTS: The longest documented exception to Collins' Law, a
      medulloblastoma recurring 20 years and 8 months after the period of risk for
      recurrence is presented. Both the site of recurrence and the histopathology were
      identical to the original tumor. CONCLUSION: We present the longest documented
      exception to Collins' Law, to emphasize that even after decades the term "cure"
      should only be used cautiously.

PMID- 9167784
TI  - Endogenous biologic defenses to free radicals.

PMID- 9167783
TI  - Oxidative stress following traumatic brain injury in rats.
AB  - BACKGROUND: Free radicals may be involved in the pathophysiology of traumatic
      brain injury (TBI) through oxidative damage of neurovascular structures.
      Endogenous antioxidants, such as ascorbate and alpha-tocopherol, may play a
      critical role in combating these oxidative reactions and their oxidized products
      can serve as an important index of oxidative stress. METHODS: We used electron
      spin resonance (ESR) spectroscopy and in vivo spin trapping (reaction of an
      organic compound with free radical species) to detect the possible generation of
      free radicals after TBI. Injury was inflicted by a weight drop technique over the
      head (5.7 kg-cm). Rats were intravenously infused with either 1 mL, 0.1 M of the
      spin trap, alpha-phenyl-N-tert-butyl nitrone (PBN), or an equivalent volume of
      saline immediately before TBI or sham-injury. Animals were divided into four
      groups: (1) Group I: PBN-infused sham-injured, (2) Group II: PBN-infused injured,
      (3) Group III: saline-infused sham-injured, and (4) Group IV: saline-infused
      injured. Additional groups of saline-infused uninjured, saline-infused, and PBN
      infused injured animals were used for histopathology. Sixty minutes after TBI or
      sham-injury, rats were again anesthetized and decapitated. The brains were
      removed within 1 minute, homogenized, and extracted for lipids. The extracts were
      analyzed by ESR spectroscopy. Brain ascorbic acid (AA) concentration was
      determined spectrophotometrically, using the ascorbate oxidase assay. RESULTS: No
      PBN spin adduct signals (indicating trapped free radical species) were visible 60
      minutes after TBI. All groups of rats showed an ascorbyl free radical signal. The
      ascorbyl signal intensity (AI) was, however, significantly higher in the injured
      rats, while the brain (AA) was significantly reduced. In addition, the ratio of
      AI/AA, which eliminates the effect of variable ascorbate concentrations in the
      brain, was also significantly higher in the injured animals. CONCLUSIONS: We
      conclude that 60 minutes following TBI there was a significantly increased level
      of oxidative stress in the brain. This may reflect formation of free radical
      species with subsequent interaction with ascorbate (antioxidant) during the 60
      minute period. The lack of PBN spin adduct signals 1 hour after TBI may indicate
      that free radical generation is time dependent and might be detectable earlier or
      later than the 60 minute period.

PMID- 9167785
TI  - Vandals at the gates of medicine--have they been repulsed or are they over the
      top.

PMID- 9167787
TI  - Differences in cognitions during chest pain of patients with panic disorder and
      ischemic heart disease.
AB  - BACKGROUND: A significant number of patients with chest pains who undergo
      coronary angiography (20-30%) have normal coronary arteries. Up to 50% of this
      group are eventually diagnosed as Panic Disorder and most continue to complain of
      their symptoms, in spite of the normal coronary angiogram. We hypothesized that
      the cognitions of panic disorder subjects on presentation with chest pain would
      differ from those of patients suffering from true angina pectoris. METHODS: We
      investigated the cognitions associated with chest pain of three patient groups:
      proven symptomatic coronary artery disease (CAD+), subjects with chest pain and a
      normal coronary angiogram (CAD-), and patients with panic disorder (PD). All
      patients were classified according to whether the symptomatology was, firstly,
      associated with frightening cognitions (during the episode), and, secondly,
      whether either these cognitions (cognitive predominance), or the physical symptom
      (physical predominance), dominated the clinical picture. RESULTS: We observed
      that in the CAD+ group, 18% experienced frightening cognitions but in only 4% (2
      of 66 patients) were the cognitions the dominant experience during the chest
      pain. In contrast, all the PD patients experienced frightening cognitions and in
      83% of this group, the cognitions were the predominant experience. In the CAD-
      group, 48% were found to be PD compatible. CONCLUSIONS: This study indicates that
      the cognitions of patients during episodes of chest pain, evaluated by three
      questions, help to differentiate between PD and true coronary symptoms.
      Consequently, the presence of frightening cognitions in the presence of chest
      pain, particularly at the onset of the clinical problem, makes necessary the need
      for psychiatric evaluation with the objective of excluding PD.

PMID- 9167786
TI  - Profile of a large sample of patients with social phobia: comparison between
      generalized and specific social phobia.
AB  - This study examines a large cohort of subjects with social phobia, as part of a
      larger naturalistic and longitudinal study of 711 subjects with anxiety
      disorders. We focused on 176 subjects who were in an episode of social phobia at
      intake. We were particularly interested in evaluating the diagnostic distinction
      between generalized and specific social phobia. We compared these two groups
      along demographic characteristics, comorbidities, psychosocial functioning
      (health, role functioning, social functioning, and emotional functioning) and
      global assessment scores. We found that generalized social phobics tended to have
      an earlier age of onset as compared to the specific group; however, this is not a
      statistically significant difference at this level of analysis. The two groups
      did not differ for the current comorbidities examined. We observed no differences
      in the treatment received by the two types of social phobia subjects, and the two
      groups functioned equally well in terms of health and fulfilling social roles. In
      addition, we examined adverse childhood events (i.e., death of a parent,
      childhood abuse) and found no evidence for any differential impact these events
      might have on the type of social phobia. Although we did observe significantly
      greater fear of public speaking among the specific compared to the generalized
      group, which may indicate a qualitative difference between the subtypes, our
      results suggest that for most parameters, generalized and specific social phobia
      represent a continuum of similar and overlapping entities.

PMID- 9167788
TI  - Core symptom pattern of social phobia.
AB  - Using self-rating questionnaires, 63 patients with social phobia but without a
      history of spontaneous panic attacks reported on their symptoms and traits, and
      on the development of their social phobia. The anxiety responses were composed of
      many symptoms (median = 14) of marked intensity, with blushing, trembling,
      cognitive difficulties, communication difficulties, and fears of the impression
      they make on others as cardinal symptoms. In contrast to the symptom pattern seen
      in spontaneous panic attacks, dizziness, chest discomforts, and difficulty in
      getting air were infrequent. The acute responses were generally followed by
      prolonged reactions with depressed mood, lowered self-esteem, and increased fears
      of similar situations. Most often the anticipatory anxiety was both intense and
      of long duration. Marked childhood traits of insecurity were reported by some
      patients, but these traits did not seem to be a general forerunner of the social
      phobia. Most patients had a gradual onset of the disorder between the age of ten
      and twenty, with increasing traits of social insecurity and anxiety responses
      developing simultaneously, during a period when a group of healthy controls
      reported that their insecurity was decreasing.

PMID- 9167789
TI  - Subclinical obsessive-compulsive disorder in college students.

PMID- 9167790
TI  - Age and gender effects on obsessive-compulsive symptoms in children and adults.

PMID- 9167791
TI  - Current status of pharmacotherapy for PTSD: an effect size analysis of controlled
      studies.

PMID- 9167792
TI  - Panic attacks caused by temporal tumors: an exemplary new case and a review.
AB  - A patient is described with a ruptured temporal cavernous hemangioma clinically
      presenting with recurrent panic attacks mimicking panic disorder. The role of
      temporal lobe structures in the pathogenesis of anxiety spells is highlighted,
      reviewing the published cases of temporal tumors leading to panic attacks.

PMID- 9167793
TI  - Inter-relationships among measures commonly used in research on social phobia.

PMID- 9167794
TI  - Paruresis and urine drug testing.

PMID- 9167795
TI  - Citalopram and panic disorder.

PMID- 9167796
TI  - Misuse of loperamide in anxiety disorder patients.

PMID- 9167797
TI  - Behavior change communication strategies.
AB  - Appropriate and effective communication is central to the success of
      interventions to reduce the risk of HIV infection. This paper reviews what has
      been learned about the nature of communication in the behavior change process. It
      examines the contexts in which communication occurs, as well as the contribution
      of communication theory, social marketing theory, and structural intervention
      theory to intervention development. Guidance is offered on the most appropriate
      ways in which to communicate with different groups and audiences, and future
      priorities for research and intervention are identified.

PMID- 9167798
TI  - HIV counseling for behavior change.
AB  - The purpose of this paper was to provide a framework for discussion in the
      working group on HIV Counseling for Behavior Change at the Third USAID HIV/AIDS
      Prevention Conference. The paper begins with a section defining HIV counseling
      and describing different types of HIV counseling. Next, points of consensus and
      controversy regarding the conduct and evaluation of HIV counseling are discussed.
      This is followed by a section outlining findings to date on the effectiveness of
      HIV counseling, and a discussion of methodological issues in evaluating
      counseling outcomes. Finally, the paper includes a list of key issues for further
      research.

PMID- 9167799
TI  - Evaluation of HIV/STD prevention, care and support: an update on WHO's
      approaches.
AB  - Over the past decade only a limited number of public health initiatives have been
      subjected to systematic monitoring and evaluation and, in many instances, there
      is growing pressure to estimate which approaches work best for a given level of
      inputs in order to allocate resources effectively. However, evaluation is very
      often seen as punitive, and a change in perception is needed to allow evaluation
      to be owned by all stakeholders in public programs. In the field of HIV/AIDS
      prevention and care, the first difficulty is that many national AIDS programs
      lack clearly stated objectives and involve a wide variety of players. These
      players each have their own guidelines for project/program design, monitoring,
      and evaluation. The second difficulty relates to the fact that evaluation
      involves "multiple methods, multiple audiences, multiple funding sources,
      multiple perspectives, multiple paradigms, multiple roles, and multiple solutions
      to multiple problems" (Quinn Patton, 1986). To some people, evaluation calls for
      complex experimental studies while to others it means pausing at the end of an
      activity to sort out what went well and what went less successfully. This paper
      examines briefly some of the problems and challenges facing the evaluation of HIV
      prevention and care and summarizes the approaches adopted by the World Health
      Organization (WHO) to assist AIDS programs around the world in evaluating their
      initiatives. The paper also provides an update on the progress of developments,
      training, and implementation of these approaches.

PMID- 9167800
TI  - Characteristics of risk-taking behaviors, HIV and AIDS knowledge, and risk
      perception among young males in southwest China.
AB  - A cross-sectional survey was undertaken to describe risk-taking behaviors and to
      assess the knowledge and risk perception of HIV and AIDS among young males aged
      18 to 29 years in 82 villages in Longchuan, Yunnan, China, in 1994. Information
      on demographic, behavioral, and drug-using factors, and knowledge of HIV
      transmission and prevention, and risk perception was collected using an
      interviewer-administered anonymous questionnaire. A total of 1,548 individuals
      were interviewed and 433 drug users, including 52 nonsharing injectors and 140
      sharing injectors, were identified. Over half the individuals scored 0 on HIV
      knowledge, but knowledge was greater among nonsharing drug injectors. Most drug
      injectors had initiated drug injection after 1990. The reported incidence
      continues to increase in all three major ethnic groups. Sharing of equipment was
      common (73%) among injectors. Drug users were four times more likely to have had
      premarital or extramarital sex, but condoms were used by only 2.5%. Thus, factors
      promoting spreading of HIV are common in this area. We recommend that a community
      based intervention program, targeting both young men and women, be implemented
      and evaluated in Longchuan as soon as possible.

PMID- 9167802
TI  - Single Thai women's interpersonal communication and mass media reception on AIDS.
AB  - This research examines young unmarried women's ways of talking about AIDS, AIDS
      prevention, and its relationship to mass media AIDS messages in Thailand. Data
      were derived from a survey conducted in four districts of Kanchanaburi province.
      Three hundred ninety-seven unmarried women were extracted from the approximately
      1,800 original subjects for this analysis. Respondents were asked about the
      subjects and extent of their conversations about AIDS, the choice of discussion
      partners, considerations of social appropriateness in talking about the disease,
      as well as their risk perception. Important findings were that (a) women tend to
      talk about AIDS primarily with friends and siblings, (b) their reception level of
      mass media messages is related to the number of topics discussed and frequency of
      talks by the subjects, and (c) socioeconomic status and age are related to the
      variety and frequency of talking about AIDS. Implications for AIDS education are
      discussed.

PMID- 9167801
TI  - Risk contexts and risk behaviors in the Euregion Maas-Rhein: the Boule de Neige
      intervention for AIDS prevention among drug users.
AB  - Using targeted sampling, self-reported data of 1,767 drug users in the Euregion
      Maas-Rhein were collected over 3 years. Forty-two percent of the injection drug
      users shared syringes with sexual partners and 47.8% with friends. Eighty-one
      percent of the total sample had sexual contact in the last 6 months, half of whom
      with one person and half with two or more. Significant predictors of high-risk
      drug use were injecting in the presence of others, injection onset before the age
      of 20, female gender, and not living in The Netherlands. Participation in needle
      exchange or methadone programs and sufficient knowledge of risk factors was not
      significantly related to a reduction of high-risk drug use behavior. High-risk
      sexual behavior was found to be related to male gender, under the age of 30 and
      to multiple sexual partners. We conclude that in a social context where needle
      exchange, methadone programs, and sufficient knowledge of risk factors among the
      drug user population exist, AIDS prevention can be improved through behavioral
      skills training and developing specific interventions that target the peer group
      environments, rituals, partner relationships, and lifestyles of drug users.

PMID- 9167803
TI  - I have often wondered...

PMID- 9167804
TI  - Winner of the 1996 Cabaud Award. The effect of lifelong exercise on canine
      articular cartilage.
AB  - The effect of long-term exercise on canine knees was studied to determine whether
      an increased level of lifelong weightbearing exercise causes degeneration, or
      changes that may lead to degeneration, of articular cartilage. Eleven dogs were
      exercised on a treadmill at 3 km/hr for 75 minutes 5 days a week for 527 weeks
      while carrying jackets weighing 130% of their body weight. Ten control dogs were
      allowed unrestricted activity in cages for the 550 weeks. At the completion of
      the study all knee joints were inspected for evidence of joint injury and
      degeneration. Articular cartilage surfaces from the medial tibial plateau were
      examined by light microscopy, the cartilage thickness was measured, and the
      intrinsic material properties were determined by mechanical testing. No joints
      had ligament or meniscal injuries, cartilage erosions, or osteophytes. Light
      microscopy did not demonstrate cartilage fibrillation or differences in safranin
      O staining of the tibial articular cartilages between the two groups.
      Furthermore, the tibial articular cartilage thickness and mechanical properties
      did not differ between the two groups. These results show that a lifetime of
      regular weightbearing exercise in dogs with normal joints did not cause
      alterations in the structure and mechanical properties of articular cartilage
      that might lead to joint degeneration.

PMID- 9167805
TI  - Long-term results of anterior cruciate ligament reconstruction with a Dacron
      prosthesis. The frequency of osteoarthritis after seven to eleven years.
AB  - In this prospective study we investigated 70 patients with chronic anterior
      instability who underwent anterior cruciate ligament reconstruction with a Dacron
      prosthesis. Fifty-five (79%) patients could be followed up at a mean of 9 years.
      Within the follow-up time, 44% (29 of 66) of the prostheses were diagnosed as
      ruptured; the annual rupture frequency was 5%. Second reconstructions were
      performed for 20 patients (29%), 5 patients had third reconstructions, and 9
      patients wanted no further surgical treatment. Fifty-two patients (74% of the
      original group) underwent radiographic examination. Eighty-three percent (43) of
      these patients had radiographic changes in the operated knee, and 40% (21 of 52)
      had joint space reduction up to 50%. The rate of radiographically detected
      osteoarthritis was increased 10 times compared with the normal knee. Patients
      with medical instability and patients older than 30 years at the initial
      operation had more severe osteoarthritic changes. Based on the functional results
      of the patients with a ligament in place after 9 years, only 14% (10) of the
      original group had acceptable stability and knee function.

PMID- 9167806
TI  - Arthroscopic capsular release for the stiff shoulder. Description of technique
      and anatomic considerations.
AB  - The anatomic proximity of several neurovascular structures remains a major
      concern to the surgeon interested in performing arthroscopic capsular release. We
      evaluated the anatomic relationships between the released capsule and the
      axillary nerve, posterior circumflex humeral artery, and brachial artery in a
      frozen cadaveric model. With the aid of electrocautery, seven cadaveric shoulders
      underwent complete arthroscopic capsular release. The release was performed
      circumferentially, approximately 1 cm lateral to the glenoid rim. All shoulders
      were subsequently frozen and sectioned through the plane of the capsular release
      while the shoulder was maintained in the lateral arthroscopic position (45
      degrees of abduction and 20 degrees of flexion). Anatomic dissection revealed an
      average distance from the capsular release to the axillary nerve of 7.04 mm (95%
      confidence interval, 5.62, 8.47), to the posterior circumflex humeral artery of
      8.2 mm (95% confidence interval, 6.41, 9.99), and to the brachial artery of 15.97
      mm (95% confidence interval, 9.85, 22.09). As the axillary nerve was followed
      medially from the released capsule, the inferior border of the subscapularis
      muscle became interposed between the capsule and the axillary nerve. This limited
      anatomic study shows that a relatively safe margin between the capsule and the
      neighboring neurovascular structures can be obtained by releasing the capsule
      within 1 cm of the glenoid rim.

PMID- 9167807
TI  - Arthroscopic treatment of partial rotator cuff tears in young athletes. A
      preliminary report.
AB  - Forty-three athletes under age 40, more than half of which were collegiate or
      professional, with partial rotator cuff tears were treated arthroscopically and
      observed for a minimum of 24 months. By history and mechanism of injury, two main
      groups were identified. Group A had 14 patients with acute, traumatic injuries.
      All 14 had inflamed subacromial bursas, but increased glenohumeral translation
      and labral lesions were uncommon. Twelve patients (86%) had satisfactory
      postoperative results and nine (64%) returned to preinjury sports after
      arthroscopic subacromial decompression and tear debridement. Group B had 29
      overhead athletes with insidious, atraumatic shoulder pain. They were not as
      successful with debridement (19 [66%] satisfactory and 13 [45%] return to
      preinjury sports). Within Group B, three subgroups were identified based on the
      examination under anesthesia and subacromial inflammation. Group B1 (8 patients)
      had normal-appearing subacromial spaces and often increased anterior glenohumeral
      translation with posterior labral tears. These patients did poorly after
      arthroscopic tear debridement (3 [38%] satisfactory and 2 [25%] return to
      sports). Group B2 (12 patients) had inflamed subacromial bursas and increased
      glenohumeral translation. This group had marginal results with debridement (7
      [58%] satisfactory and 6 [50%] return to sports). Group B3 (9 patients) with
      subacromial inflammation, yet without increased glenohumeral translation, had
      excellent pain relief (100%) but less than half (4) returned to preinjury sports.

PMID- 9167808
TI  - Pathologic changes associated with shoulder dislocations. Arthroscopic and
      physical examination findings in first-time, traumatic anterior dislocations.
AB  - This prospective observational study was performed on young patients, less than
      24 years old, with first-time, traumatic anterior shoulder dislocations. These
      patients were offered either arthroscopic or nonoperative treatment. Fifty-three
      patients chose nonoperative treatment. Sixty-three patients elected to have
      arthroscopic procedures. The average patient age was 19.6 years. There were 59
      men and 4 women. All procedures were performed within 10 days of dislocation. All
      63 patients had hemarthrosis. Sixty-one of 63 (97%) patients treated surgically
      had complete detachment of the capsuloligamentous complex from the glenoid rim
      and neck (Perthes-Bankart lesion), with no gross evidence of intracapsular
      injury. Of the other two patients, one had an avulsion of the inferior
      glenohumeral ligament from the neck of the humerus, and one had an interstitial
      capsular tear adjacent to the intact glenoid labrum. Fifty-seven patients had
      Hill-Sachs lesions; none were large. There were six superior labral anterior
      posterior lesions, two with detachment of the biceps tendon. There were no
      rotator cuff tears. Of the 53 nonoperatively treated patients, 48 (90%) have
      developed recurrent instability. In this population, the capsulolabral avulsion
      appeared to be the primary gross pathologic lesion after a first-time
      dislocation. These findings, associated with the 90% nonoperative recurrence
      rate, suggest a strong association between recurrent instability and the Perthes
      Bankart lesion in this population.

PMID- 9167809
TI  - Treatment of plantar fasciitis by iontophoresis of 0.4% dexamethasone. A
      randomized, double-blind, placebo-controlled study.
AB  - Plantar fasciitis is a common problem in running sports. This study was
      undertaken to determine whether iontophoresis of dexamethasone in conjunction
      with other traditional modalities provides more immediate pain relief than
      traditional modalities alone. Forty affected feet were randomly assigned to one
      of two groups. Group I feet were treated with traditional modalities and placebo
      iontophoresis. Group II feet received the traditional modalities plus
      iontophoresis of dexamethasone. Both groups were treated six times over 2 weeks.
      The subjects' clinical course was assessed using the Maryland Foot Score. At the
      conclusion of treatment, Group II patients had significantly greater improvement
      than Group I patients (increase on Maryland Foot Score of 6.8 +/- 5.6 for Group
      II and 3.1 +/- 4.1 for Group I). However, at followup 1 month after completion of
      treatment there was no significant difference between groups (increase of 5.6 +/-
      8.0 for Group I and 7.4 +/- 6.3 for Group II). These results suggest that
      although traditional modalities alone are ultimately effective, iontophoresis in
      conjunction with traditional modalities provides immediate reduction in symptoms.
      Based on these results, iontophoresis of dexamethasone for plantar fasciitis
      should be considered when more immediate results are needed (i.e., performance
      athletes and active patients.

PMID- 9167810
TI  - Impact loading of the lumbar spine during football blocking.
AB  - The purpose of our study was to determine the impact force to the lumbar spine
      when football players hit a blocking sled. We quantified the loads at the L4-5
      motion segment throughout the blocking sequence. Five Division I-A college
      football linemen were subjects for our study. Kinematic data were obtained while
      the subjects hit a blocking sled instrumented with a force plate. Three plane
      forces were then calculated from these data. The average impact force measured at
      the blocking sled was 3013 +/- 598 N. The average peak compression force at the
      L4-5 motion segment was 8679 +/- 1965 N. The average peak anteroposterior shear
      force was 3304 +/- 1116 N, and the average peak lateral shear force was 1709 +/-
      411 N. The magnitude of the loads on the L4-5 motion segment during football
      blocking exceed those determined during fatigue studies to cause pathologic
      changes in both the lumbar disk and the pars interarticularis. These data suggest
      that the mechanics of repetitive blocking may be responsible for the increased
      incidence of lumbar spine injury incurred by football linemen.

PMID- 9167811
TI  - The effect of a pneumatic leg brace on return to play in athletes with tibial
      stress fractures.
AB  - A total of 18 competitive and recreational athletes were enrolled in a
      randomized, prospective study looking at the effect of pneumatic leg braces on
      the time to return to full activity after a tibial stress fracture. All patients
      had positive bone scans and 15 had positive radiographic findings by Week 12.
      There were two treatment groups. The traditional treatment group was treated with
      rest and, after 3 pain-free days, a gradual return to activity. The pneumatic leg
      brace (Aircast) group had the brace applied to the affected leg and then followed
      the same return to activity guidelines. The guidelines consisted of a detailed
      functional progression that allowed pain-free return to play. The brace group was
      able to resume light activity in 7 days (median) and the traditional group began
      light activity in 21 days (median). The brace group returned to full,
      unrestricted activity in 21 +/- 2 days, and the traditional group required 77 +/-
      7 days to resume full activity. The Aircast pneumatic brace is effective in
      allowing athletes with tibial stress fractures to return to full, unrestricted,
      pain-free activity significantly sooner than traditional treatment.

PMID- 9167812
TI  - Fibular grooving for recurrent peroneal tendon subluxation.
AB  - Twelve ankles in 11 consecutive patients with recurrent peroneal tendon
      dislocations were studied after undergoing a fibular grooving procedure. The mean
      age of the patients was 25 years (range, 13 to 45). The mean time from initial
      injury to surgery was 18 months, and the mean follow-up time was 6 years. All
      patients had preoperative peroneal tenderness; 9 of 12 ankles had active peroneal
      tendon subluxation on examination. All patients had failed results from
      nonoperative treatments of rehabilitation and bracing. Before the fibular
      grooving procedure, 10 ankles were shown to have intraarticular pathologic
      changes on arthroscopic evaluation. Postoperatively, there were no
      resubluxations. Eleven ankles were pain-free, 10 had full and symmetric range of
      motion, and 1 patient lost 3 degrees of eversion. Ten patients were able to
      return to full unrestricted activities including all previous sports. Eleven
      ankles were rated as excellent results. Complications included suture abscesses
      in two patients and refractory pain in one patient who had multiple surgeries for
      subtalar pain but had no peroneal resubluxation. Recurrent peroneal tendon
      subluxation is an uncommon problem. An accurate diagnosis is essential. The
      fibular grooving procedure appears to reproducibly alleviate resubluxation of the
      peroneal tendons and diminish pain. It also allows for retainment of motion and
      subsequent return to work and sports with a high satisfaction rate.

PMID- 9167813
TI  - The effects of joint position and direction of joint motion on proprioceptive
      sensibility in anterior cruciate ligament-deficient athletes.
AB  - We studied a group of anterior cruciate ligament-deficient athletes to identify
      whether joint position and direction of joint motion have a significant effect on
      proprioception. Twenty-nine anterior cruciate ligament-deficient athletes were
      tested for their threshold to detect passive motion at both 15 degrees and 45
      degrees moving into the directions of both flexion and extension. The single
      legged hop test was used to identify function in the deficient limb. Results
      demonstrated statistically significant deficits in threshold to detect passive
      motion for the deficient limb at 15 degrees moving into extension. For the
      deficient limb, threshold to detect passive motion was significantly more
      sensitive moving into extension than flexion at a starting angle of 15 degrees;
      at a starting angle of 15 degrees moving into extension threshold was
      significantly more sensitive than at a starting angle of 45 degrees moving into
      extension. We conclude that in deficient limbs proprioception is significantly
      more sensitive in the end ranges of knee extension (15 degrees) and is
      significantly more sensitive moving into the direction of extension. To
      effectively restore reflex stabilization of the lower limb we recommend a
      rehabilitation program emphasizing performance-based, weightbearing, closed
      kinetic chain exercise for the muscle groups that act on the knee joint.

PMID- 9167814
TI  - Epidemiology of anterior cruciate ligament injuries in soccer.
AB  - We did a retrospective study of all anterior cruciate ligament injuries (972)
      verified by arthroscopic evaluation at hospitals in the Hordaland region of
      Norway from 1982 to 1991. Our final study group comprised 176 patients who had
      participated in organized soccer and answered a questionnaire. The overall
      incidence rate was 0.063 injuries per 1000 game hours. Men incurred 75.6% (133)
      of the injuries. Women had an incidence rate of 0.10 injuries per 1000 game
      hours, significantly higher than that for men (0.057). The incidence rate was
      higher (0.41) for men in the top three divisions. Most of the injuries (124)
      occurred during games. Contact injuries from tackling was the injury mechanism in
      46.0% of the cases. Players on the offensive team incurred 122 (69.3%) of the
      injuries. Reconstructive surgery was performed on 131 (74.4%) of the injured
      players and was found necessary for return to a high level of play. Half of the
      players (87) returned to soccer; men at high levels of play had the highest
      return rate (88.9%), and men over age 34 had the poorest return rate (22.9%).
      Nearly one-third of the injured athletes gave up soccer because of poor knee
      function or fear of new injury.

PMID- 9167815
TI  - Isometry measurements in the knee with the anterior cruciate ligament intact,
      sectioned, and reconstructed.
AB  - When assessing isometry during anterior cruciate ligament surgery, it is assumed
      that points determined to be isometric remain so after reconstruction. We sought
      to evaluate if isometric measurements vary with the status of the anterior
      cruciate ligament. A computerized electronic isometer was used to measure the
      magnitude and pattern of change in separation distance between a constant point
      in the tibial insertion of the anterior cruciate ligament and five positions
      within the femoral insertion with the anterior cruciate ligament intact,
      sectioned, and reconstructed. For the center position, the magnitude and pattern
      of the change in separation distance was physiologically isometric in all
      conditions (maximal length change, 3.0 mm). For the posterior position, the
      isometry pattern remained physiologic in each condition, and the magnitude of the
      separation distance was nearly isometric in all conditions (maximal length
      change, 3.7 mm). The superior and inferior positions had similar isometric
      measurements in the intact and sectioned conditions but significantly different
      measurements after anterior cruciate ligament reconstruction. Intraoperative
      assessment of isometry at positions in the center or posterior portion of the
      anterior cruciate ligament's femoral insertion provides useful information that
      is not altered by reconstruction. For superior and inferior positions, however,
      points found to be isometric in the anterior cruciate ligament-deficient knee did
      not remain isometric after reconstruction.

PMID- 9167816
TI  - The effect of functional knee bracing on the anterior cruciate ligament in the
      weightbearing and nonweightbearing knee.
AB  - We investigated the effect of functional bracing on anterior cruciate ligament
      strain in humans by arthroscopic implantation of a differential variable
      reluctance transducer on the ligament and measurement of its strain behavior.
      Strains were measured while "injury mechanism" loads were applied to the
      weightbearing and nonweightbearing knees for both braced and unbraced conditions.
      For the unbraced knee, there was a significant increase in ligament strain values
      when subjects went from a seated position (minimal shear and compressive loads
      across the knee) to a standing posture (substantial shear and compressive loads
      across the knee). Similar strain values were found between these same seated and
      standing postures when a 140-N anterior-directed load was applied to the tibia.
      This indicates that the ligament is strained during weightbearing and
      demonstrates that the compressive load across the knee produced during
      weightbearing does not significantly reduce ligament strain values in comparison
      with the unweighted joint with relaxed muscles for the 140-N load limit of our
      anterior shear test. Bracing produced a protective effect on the ligament by
      significantly reducing the strain values for anterior-directed loading of the
      tibia up to 140 N with the knee in both weightbearing and nonweightbearing
      conditions. Likewise, bracing produced a protective effect on the ligament by
      significantly reducing strain values in response to internal-external torque of
      the tibia up to 6 N-m with the knee nonweightbearing. The brace strap that
      contacts the tibia just distal to the insertion of the patellar tendon was
      instrumented with a load sensor, allowing us to measure the posterior-directed
      loads applied by the brace to the tibia. Adjustment of strap tension between low
      and high settings did not modulate the protective effect of the brace on the
      ligament.

PMID- 9167817
TI  - Knee injuries in women collegiate rugby players.
AB  - We evaluated the prevalence and patterns of knee injuries in 810 women collegiate
      rugby players. Injuries that resulted in players missing at least one game were
      recorded and a questionnaire was used to delineate players' rugby and knee injury
      history. There were 76 total knee injuries in 58,296 exposures. This resulted in
      a 1.3 knee injury rate per 1000 exposures. Twenty-one anterior cruciate ligament
      tears were reported for a 0.36 incidence per 1000 exposures. Other injuries
      included meniscal tears (25), medical collateral ligament sprains (23), patellar
      dislocations (5), and posterior cruciate ligament tears (2). Sixty-one percent of
      the medial collateral ligament sprains occurred in rugby forwards and 67% of
      anterior cruciate ligament tears occurred in rugby backs. All other injuries
      occurred with equal frequency in backs and forwards. This study demonstrates that
      knee injury rates in women's collegiate rugby are similar to those reported for
      other women's collegiate sports. The overall rate of anterior cruciate ligament
      injury in women's rugby, however, is slightly higher than that reported for women
      soccer and basketball players.

PMID- 9167818
TI  - Lumbar mobility and low back pain during adolescence. A longitudinal three-year
      follow-up study in athletes and controls.
AB  - In this 3-year longitudinal study, we studied lumbar mobility and the occurrence
      of low back pain among 98 adolescents who were free of previous severe low back
      pain: 33 nonathletes (16 boys, 17 girls), 34 boy athletes (ice hockey and soccer
      players) and 31 girl athletes (figure skaters and gymnasts). During the followup,
      low back pain lasting longer than 1 week was reported by 29 athletes (15 boys and
      14 girls) and by 6 nonathletes (3 boys and 3 girls). In multivariate analyses,
      participation in sports and low maximal lumbar flexion at the baseline predicted
      low back pain during the followup among boys; however, these factors accounted
      for only 16% of the variability between the groups with and without low back
      pain. Among girls, decreased range of motion in the lower lumbar segments, low
      maximal lumbar extension, and high body weight at the baseline were predictive of
      low back pain during the followup, accounting for 31% of the variability between
      the groups. The girls in the lowest tertile of maximal lumbar extension at
      baseline had a relative risk of 3.4 to have future low back pain compared with
      those in the highest tertile. We conclude that the low individual physiologic
      maximum of lower segment lumbar extension mobility may cause overloading of the
      low back among athletes involved in sports with frequent maximal lumbar extension
      and that it predicts future low back pain.

PMID- 9167819
TI  - Shoulder muscle firing patterns during the windmill softball pitch.
AB  - The purpose of this study was to describe the activity of eight shoulder muscles
      during the windmill fast-pitch softball throw. Ten collegiate female pitchers
      were analyzed with intramuscular electromyography, high-speed cinematography, and
      motion analysis. The supraspinatus muscle fired maximally during arm elevation
      from the 6 to 3 o'clock position phase, centralizing the humeral head within the
      glenoid. The posterior deltoid and teres minor muscles acted maximally from the 3
      to 12 o'clock position phase to continue arm elevation and externally rotate the
      humerus. The pectoralis major muscle accelerated the arm from the 12 o'clock
      position to ball release phase. The serratus anterior muscle characteristically
      acted to position the scapula for optimal glenohumeral congruency, and the
      subscapularis muscle functioned as an internal rotator and to protect the
      anterior capsule. Although the windmill softball pitch is overtly different from
      the baseball pitch, several surprising similarities were revealed. The serratus
      anterior and pectoralis major muscles work in synchrony and seem to have similar
      functions in both pitches. Although the infraspinatus and teres minor muscles are
      both posterior cuff muscles, they are characteristically uncoupled during the 6
      to 3 o'clock position phase, with the infraspinatus muscle acting more
      independently below 90 degrees. Subscapularis muscle activity seems important in
      dynamic anterior glenohumeral stabilization and as an internal rotator in both
      the baseball and softball throws.

PMID- 9167820
TI  - Anteromedial tibial tubercle transfer in patients with chronic anterior knee pain
      and a subluxation-type patellar malalignment.
AB  - We performed a prospective analysis of 29 Fulkerson anteromedial tibial tubercle
      transfers in patients with chronic anterior knee pain. The average followup was
      32 months (range, 25 to 44). Fourteen patients (Group 1) had subluxation-type
      malalignment (congruence angle > 20 degrees, tilt angle > 8 degrees) and were
      treated with an isolated anteromedial tibial tubercle transfer. Fifteen patients
      (Group 2) had combined subluxation and tilt malalignment (congruence angle > 20
      degrees, tilt angle < 8 degrees) and underwent anteromedial tibial tubercle
      transfer combined with a lateral release. Pre- and postoperative evaluations
      included clinical and radiographic examinations, Lysholm and Kujala
      patellofemoral scores, and standing-alignment computed tomography scans in 15
      degrees of flexion taken transversely at the midpatellar. In all but one patient
      a dramatic improvement in Lysholm and Kujala scores was noted. The congruence
      angle improved in all patients except one, with an average improvement of 16
      degrees in Group 1 and of 14 degrees in Group 2. The tilt angle remained
      relatively unchanged (change, -0.5 degree) in Group 1, but it improved by 11
      degrees in Group 2. We conclude that an isolated anteromedial tibial tubercle
      transfer can consistently improve patellar subluxation and, when combined with a
      lateral release, can improve patellar subluxation and tilt, resulting in improved
      functional scores for patients with chronic anterior knee pain.

PMID- 9167821
TI  - Accuracy of imaging the menisci on an in-office, dedicated, magnetic resonance
      imaging extremity system.
AB  - Magnetic resonance imaging effectively defines and characterizes musculoskeletal
      pathologic lesions, particularly meniscal tears. Most studies comparing the
      efficacy of magnetic resonance imaging and arthroscopic evaluation have been
      performed on high-field (1.5-T) systems. The effectiveness of a low-field (0.2
      T), dedicated, extremity magnetic resonance imaging device in diagnosing meniscal
      tears was studied prospectively on 35 patients with knee symptoms who
      subsequently had arthroscopic evaluation. Magnetic resonance imaging examinations
      were performed before surgery and were read by an experienced radiologist who was
      blinded to the results of the arthroscopic evaluations. Specificity was 100% for
      both the medial and lateral menisci. Sensitivity was 86% for the medial menisci,
      89% for the lateral menisci, and 87% for both. Accuracy was 91% for the medial
      menisci, 97% for the lateral menisci, and 94% overall. The positive predictive
      values were 100% for the medial menisci, 100% for the lateral menisci, and 100%
      for both. The negative predictive values were 81% for the medial menisci, 96% for
      the lateral menisci, and 91% for both. The low-field magnetic resonance imaging
      system provided specificity and sensitivity that were equal to or better than
      previous reports with high-field systems. In particular, this low-field system
      eliminated the problem of false-positive results that has been found in some
      studies using high-field systems.

PMID- 9167822
TI  - Diagnosis of anterolateral ankle impingement. Comparison between magnetic
      resonance imaging and clinical examination.
AB  - We reviewed 22 patients who had arthroscopic evaluations and preoperative
      magnetic resonance imaging studies of their ankles because of chronic
      anterolateral ankle pain after sprains. The ability of surgeons to use the
      initial clinical examination to predict arthroscopically confirmed anterolateral
      ankle impingement was compared with the ability to predict this condition using
      preoperative magnetic resonance imaging. The patient population consisted of 15
      men and 7 women who had an average age of 28 years. Five patients (23%) were
      intercollegiate athletes and 17 patients (77%) were recreational athletes. All
      patients reported previous traumas to the involved ankles, and all were seen with
      chronic ankle pain. Clinical examinations were used to assess ankle pain,
      swelling, range of motion, and stability. Anterolateral ankle impingement was
      confirmed in 18 patients (82%) with arthroscopic examination. Clinical
      examinations had a sensitivity of 94% and a specificity of 75% for predicting
      impingement, and magnetic resonance imaging had a sensitivity of 39% and a
      specificity of 50%. The results of this study suggest that preoperative magnetic
      resonance imaging examination is not beneficial or cost-effective in the
      diagnosis of anterolateral ankle impingement; furthermore, its use may cause
      further delay in treatment.

PMID- 9167823
TI  - The effect of a wrist brace on injury patterns in experimentally produced distal
      radial fractures in a cadaveric model.
AB  - We compared patterns of bony and ligamentous injury with distal radial fractures
      in braced and unbraced wrists using 20 paired fresh cadaveric upper extremities.
      A commercially available wrist brace was placed on one wrist in each pair.
      Specimens were then placed in a fast-loading gravity-driven device and subjected
      to loads averaging 16 kg from an average height of 78 cm. Postfracture
      radiographs were obtained, the specimens were dissected, and fracture patterns
      and ligamentous integrity were assessed. The following fracture types were
      produced: distal radial fractures (eight unbraced, seven braced) and
      intraarticular (seven unbraced, four braced). Radiographically, seven unbraced
      wrists demonstrated carpal bone fracture and one braced wrist demonstrated carpal
      fractures. Eight unbraced and three braced wrists sustained carpal intrinsic
      ligament injuries, four unbraced and one braced wrists demonstrated extrinsic
      ligament injuries. More capsular tears occurred in the unbraced group (N = 8)
      than in the braced group (N = 1). This model demonstrated a difference in the
      patterns of injury in unbraced and braced wrists subjected to the same mechanical
      conditions, which suggests that use of a wrist brace may alter patterns of wrist
      injury.

PMID- 9167824
TI  - Obturator nerve entrapment. A cause of groin pain in athletes.
AB  - Chronic groin pain in athletes is often difficult to diagnose and treat. There
      are many anatomic structures in the inguinal and groin region that have the
      potential to cause pain. We report 32 cases of a previously undescribed condition
      in athletes of "obturator neuropathy," a fascial entrapment of the obturator
      nerve where it enters the thigh. This condition represents a type of groin pain
      in athletes that is treatable by surgical means. There is a characteristic
      clinical pattern of exercise-induced medial thigh pain commencing in the region
      of the adductor muscle origin and radiating distally along the medial thigh.
      Needle electromyography demonstrates denervation of the adductor muscles.
      Surgical neurolysis treatment provides the definitive cure of this problem, with
      athletes returning to competition within several weeks of treatment. The surgical
      findings are entrapment of the obturator nerve by a thick fascia overlying the
      short adductor muscle. The role of conservative treatment in the management of
      this condition is unknown at present.

PMID- 9167825
TI  - Partial vascular occlusion causing pseudocompartment syndrome of the leg. A case
      report.

PMID- 9167826
TI  - Ulnar diaphyseal stress fracture in a bowler.

PMID- 9167827
TI  - A statistics primer. Prevalence, incidence, relative risks, and odds ratios: some
      epidemiologic concepts in the sports medicine literature.

PMID- 9167828
TI  - Patellar taping in the treatment of patellofemoral pain--a prospective randomized
      study.

PMID- 9167829
TI  - Quality of tibial fixation in ACL reconstructions.

PMID- 9167830
TI  - Antidepressant treatment of posttraumatic stress disorder and major depression in
      veterans.
AB  - Many patients with chronic posttraumatic stress disorder (PTSD) suffer from
      comorbid major depression. The present study examines the responsiveness of such
      dual-diagnosis patients to antidepressant medication. Subjects were enrolled in
      the PTSD medication clinic at the San Diego Veterans Affairs Medical Center.
      Inclusion criteria were current diagnoses of PTSD and major depression, at least
      6 months of regular participation in the clinic, and treatment with
      antidepressant medication at therapeutic levels and durations. Exclusion criteria
      were current drug or alcohol abuse, primary psychotic illness, and poor
      compliance or frequent missed appointments. Among 72 patients meeting inclusion
      and exclusion criteria, 50% were estimated to be substantially improved, on the
      basis of Clinical Global Evaluation (CGE) scores of 2 or 1, after remaining on
      the same antidepressant treatment regimen at therapeutic doses for at least 1
      month. Antidepressant medications affecting predominantly serotonin reuptake
      (sertraline, fluoxetine) were associated with better outcomes than
      antidepressants affecting predominantly norepinephrine reuptake (nortriptyline,
      desipramine).

PMID- 9167831
TI  - Retrospective study of selegiline-antidepressant drug interactions and a review
      of the literature.
AB  - Selegiline is a selective monoamine oxidase inhibitor used in the treatment of
      Parkinson's disease. It is estimated that approximately one-half of Parkinsonian
      patients will develop depression requiring antidepressant drug treatment.
      Recently, selegiline's package insert was revised to reflect the potential risk
      of adverse effects when it is used in combination with selective serotonin
      reuptake inhibitors and tricyclic antidepressants. The objective of our study is
      to assess the safety of combining selegiline with antidepressants. A
      retrospective chart review was performed on all 28 patients with Parkinson's
      disease receiving selegiline and antidepressants concurrently to identify
      possible drug interactions. Compliance was assessed according to prescription
      refill records. Suspected adverse reactions with combination therapy were
      documented. There was a total of 40 selegiline-antidepressant drug combinations
      involving tricyclic antidepressants (n = 25), selective serotonin reuptake
      inhibitors (n = 7), trazodone (n = 5), and bupropion (n = 3). One patient
      receiving fluoxetine developed a reaction consistent with the serotonin syndrome;
      however, it was never documented as such. No other selegiline drug interactions
      were found. Adverse effects noted were typical of antidepressant monotherapy.
      Although no selegiline drug interactions were documented in our study, the
      concurrent administration of selegiline and selective serotonin reuptake
      inhibitors should be avoided because of literature-reported interactions. We
      believe that bupropion, tricyclic antidepressants, and trazodone are reasonable
      choices in combination with selegiline, although tricyclic antidepressants and
      trazodone may be reserved as second-line treatments.

PMID- 9167832
TI  - Sertraline and psychotic symptoms: a case series.
AB  - Sertraline and other SSRIs have a relatively favorable side-effect profile and
      are widely prescribed. We report the emergence of psychotic symptoms during
      treatment with sertraline in four patients. Three of these patients had a history
      of psychotic illness and were on antipsychotic medication, when sertraline was
      added. The psychotic symptoms emerged within 3 days-7 weeks of starting
      sertraline and resolved on its discontinuation. We wish to alert clinicians to
      the possibility that sertraline may provoke or exacerbate positive psychotic
      symptoms, particularly in patients on neuroleptics, with a previous history of
      psychosis.

PMID- 9167833
TI  - Combined valproate or carbamazepine and electroconvulsive therapy.
AB  - This pharmacoepidemiological study was undertaken to determine if the combination
      of electroconvulsive therapy (ECT) and the anticonvulsants valproate (VPA) or
      carbamazepine (CBZ) is safe and efficacious. The charts of seven patients
      receiving ECT and VPA or CBZ (ECT-anticonvulsant group) concurrently between May
      8, 1989, and May 9, 1993, were reviewed to determine the indication for each
      treatment, the number and type of ECT treatments, the seizure duration, adverse
      events, and the efficacy of the combination. The ECT-anticonvulsant group was
      compared to patients not treated with anticonvulsants (ECT-alone group) to
      determine if there were any differences in the two groups. Three patients had a
      marked clinical improvement, two a moderate response, one a minimal response, and
      one no response. The ECT-AC group, compared to the control group, had a shorter
      duration of seizures when unilateral treatments were used. However, there were no
      differences in the other variables compared. One patient had moderate confusion,
      and the other mild confusion and hypomania. This small case series suggests that
      the combination of ECT and anticonvulsants is safe and may be considered in
      patients for whom prophylaxis with anticonvulsant drugs is planned. Further
      controlled studies are needed to confirm our findings.

PMID- 9167834
TI  - Salutary change after frontal brain trauma.
AB  - Adverse behavioral effects of frontal traumatic brain injury are well-known.
      Patients may suffer changes in personality ranging from disinhibition to apathy.
      Beneficial effects of traumatic brain injury are rarely described. We report
      three cases of patients who sustained frontal traumatic brain injury, one of
      whose social phobia resolved and the other two of whom had an improvement in
      impulsive and antisocial behavior. In one case the brain injury may have caused
      disinhibition of an inhibited state; in the other cases disinhibition associated
      with impulsivity was replaced by a more restrained state. This adds to the data
      on the integrative role of the frontal lobes in varied psychopathologic
      conditions.

PMID- 9167836
TI  - Tardive dyskinesia and ethnicity: review of the literature.
AB  - Tardive dyskinesia (TD) is a side effect of long-term neuroleptic administration.
      The wide variation of 2 to 51% in its reported prevalence can be attributed to
      the varied definitions of TD, the use of different methods of assessment, and the
      lack of control of independent variables. Why only certain patients develop this
      side effect is an intriguing question. The occurrence of TD in family members and
      in those persons with a family history of Parkinson's disease (PD) is suggestive
      of genetic vulnerability. Further support for a genetic predisposition comes from
      the fact that only certain strains of monkeys, such as the Cebus apella strain,
      have a higher propensity to develop TD than others, such as the Macaca sepciosa
      strain. If genetic factors play a significant role in the development of TD,
      then, genetically diverse ethnic groups may have a different propensity for the
      development of TD. One method of evaluating such a possibility is to compare its
      prevalence in different countries. The current literature on ethnic differences
      in the prevalence rates of TD is reviewed. This area of study needs further
      rigorous investigation.

PMID- 9167835
TI  - The phenomenology of psychosis associated with complex partial seizure disorder.
AB  - Psychosis commonly occurs as a direct result of complex partial seizure disorder
      (CPSD). This organic mental disorder is indeed "complex" and is easily and
      frequently misdiagnosed as a variety of functional disorders, including
      schizophrenia, schizoaffective disorder, bipolar illness, psychotic depression,
      and, at best, "atypical psychosis." However, this important clinical syndrome has
      several clinical features that suggest its presence and which often permit it to
      be distinguished from other forms of psychosis. Furthermore, this disorder can be
      successfully treated with limbic anticonvulsants, with or without neuroleptics
      and/or lithium, but it is generally refractory to neuroleptic medications alone.
      In this paper, the author reviews the available literature relevant to the
      clinical phenomenology and treatment of this topic and illustrates the clinical
      profiles of 10 treatment-refractory patients admitted to a state hospital with
      previously undiagnosed psychoses secondary to CPSD. This illness needs to be
      seriously considered in the differential diagnosis of severely ill patients with
      atypical psychoses refractory to traditional treatments.

PMID- 9167837
TI  - Adolescent/adult differences in suicidal behavior and outcome.
AB  - A comprehensive literature review compared the patterns of suicide and suicidal
      behavior for adolescents and adults to identify age-related similarities and
      differences. Particular attention was given to follow-up rates of suicide by
      psychiatrically treated persons in these age groups. The major findings were that
      (1) adults and adolescent suicide completers were similar with respect to their
      gender ratio, use of guns in the attempt, completion of the initial attempt, and
      serious psychopathology; (2) adolescents differed from adults in suicidal
      behavior in their greater attempt rate, higher attempt/completion ratio, and
      lower rates of short and intermediate completion following psychiatric treatment;
      (3) the suicide outcome following psychiatric hospitalization is eightfold
      greater in adults than in youths during the first 3.5 years postdischarge; and
      (4) the 5:1 male/female ratio is the same for both adolescent attempters who
      later suicide and for all U.S. 15-19-year-old suicide completers. The frequent
      practice of combining adult and adolescent suicide and suicide behavior findings
      can result in misleading conclusions.

PMID- 9167838
TI  - The passing of a pioneer in perfluorocarbon blood substitutes.

PMID- 9167839
TI  - Perfluoro-15-crown-5-ether labelled macrophages in adoptive transfer experimental
      allergic encephalomyelitis.
AB  - In this serial in vivo study, macrophages labelled with perfluoro-15-crown-5
      ether (15C5) were monitored in rats after inducing adoptive transfer experimental
      allergic encephalomyelitis (AT-EAE). AT-EAE is an animal model of multiple
      sclerosis and is characterized by inflammatory infiltrates in the central nervous
      system (CNS) and breakdown of the blood-brain-barrier. A particular feature of AT
      EAE are macrophage infiltrates. Purpose of this study was to monitor the invasive
      and evasive phase of the macrophages in AT-EAE by using 3-dimensional 19F
      magnetic resonance imaging (3D 19F-MRI). In the early stage of the disease, a
      much stronger 19F-signal intensity was observed in AT-EAE-rats than in healthy
      control rats in the tissue adjacent to CNS regions severely affected by
      inflammatory infiltrates, and thereafter the 19F-signal intensity was decreasing
      over the time. However, no 19F-signal could be observed in the CNS itself neither
      in AT-EAE-rats nor in control rats. According to these findings it is assumed
      that we monitored the evasion of the macrophages from the region of inflammation.

PMID- 9167840
TI  - Effects of a novel perfluorocarbon emulsion on neutrophil chemiluminescence in
      human whole blood in vitro.
AB  - The effects have been studied of a novel perfluorochemical (PFC) emulsion (18.5%
      perfluorodecalin, 1.5% perfluorodimorpholine propane, 2.5% lecithin) on phorbol
      12-myristate 13-acetate (PMA; 100 micrograms ml-1)-induced neutrophil
      chemiluminescence in citrated human whole blood in vitro. A transient, dose
      dependent, decrease in chemiluminescence, to a maximum of 54% after 12 min (P <
      0.05), occurred when blood was pre-incubated with 10-40 microliters of the PFC
      emulsion, compared to saline controls. The mean (+/- s.e.m., n = 6)
      chemiluminescence of neutrophils incubated with 30 microliters emulsion at 12 min
      following PMA stimulation (9.5 +/- 1.3 mV) was significantly lower (P < 0.05)
      than control (24.2 +/- 2.2 mV). Incubation of blood with lecithin up to 16 mg ml
      1 and Pluronic F-68 or Pluronic PE 6800 up to 65 mg ml-1 did not affect
      chemiluminescence.

PMID- 9167841
TI  - Perfluorochemicals and cell biotechnology.
AB  - Perfluorochemical (PFC) liquids have properties, especially high gas solubility,
      which make these compounds useful in medicine and biotechnology. PFCs are being
      employed to facilitate respiratory gas supply to both prokaryotic and eukaryotic
      cells and, in some systems, to improve biomass production and yields of
      commercially-important cellular products. Animal (including human) and plant
      cells have also been cultured at the interface between PFC liquids and aqueous
      culture medium, while fluorocarbon polymers have been employed as gaspermeable
      membranes in eukaryotic cell cultures. This paper presents an overview of the
      applications and beneficial effects of PFCs in microbial, animal and plant
      culture systems. PFCs have been compared with other physical and chemical options
      for manipulating respiratory gas supply to cultured cells. PFC-facilitated
      improvements in cell culture technology will have increasingly important
      biotechnological implications.

PMID- 9167842
TI  - Effect of diaspirin crosslinked hemoglobin on systemic and regional blood
      circulation in pregnant rats.
AB  - Diaspirin crosslinked hemoglobin (DCLHb: Baxter Healthcare Corp., Round Lake, IL,
      USA) is a biochemically stable hemoglobin based solution with excellent oxygen
      carrying capacity. Studies have been conducted in male rats to determine the
      effect of DCLHb on systemic and regional blood circulation. However, the
      cardiovascular effect of DCLHb has not been studied in female rats. In the
      present study the effect of DCLHb (400 mg/kg, i.v.) was observed on systemic
      hemodynamic parameters and regional blood circulation in non-pregnant rats, and
      in 9-day pregnant and 18-day pregnant rats. DCLHb increased mean arterial
      pressure (MAP) and total peripheral resistance (TPR) and increased blood flow to
      the heart, gastrointestinal tract (GIT), mesentery & pancreas, and skin in all
      groups of rats. The basal blood flow to the ovaries was higher in 18-day pregnant
      rats when compared to non-pregnant and 9-day pregnant rats. DCLHb further
      increased blood flow to the ovaries of 18-day pregnant rats. It is concluded that
      DCLHb increases blood flow to the heart, GIT and skin as a result of
      redistribution of blood from the musculoskeletal system. Blood flow in female
      reproductive organs is not altered by DCLHb in non-pregnant rats and during mid
      term pregnancy. However, in advanced stages of pregnancy DCLHb increases blood
      flow to the ovaries.

PMID- 9167843
TI  - Decreased whole blood factor IX activity following hemodilution with hemoglobin A
      zero in-vitro.
AB  - Previous studies of hemoglobin-based oxygen carriers and their effects on
      coagulation have shown conflicting results. This study re-examined the effect of
      hemoglobin solution on blood coagulation in whole blood using highly purified
      human hemoglobin Ao (HbAo). Citrated human whole blood samples were diluted 1:1
      with HbAo (7gHb/dl) or human serum albumin (HSA; 5g/dl) as a protein control, and
      both activated partial thromboplastin time (aPTT) and prothrombin time (PT) were
      measured using a mechanically based whole blood coagulometer. Multiple runs were
      performed with the same volunteer donor sample. The mean aPTT time of HbAo
      diluted samples (105.9 +/- 19.9 sec., n = 41) was significantly longer than the
      undiluted controls (46.4 +/- 5.6 sec., n = 54) or HSA-diluted blood (77.1 +/-
      12.7 sec., n = 41) indicating an abnormal intrinsic coagulation pathway. There
      was no significant difference between the PT times of the HbAo and HSA-diluted
      samples. To examine the cause of the prolonged aPTT times with HbAo dilution, we
      performed activity assays of intrinsic factors XII, XI, IX, and VIII in a
      citrated human whole blood system diluted 1/5 and 1/10 with normal saline
      solution (NSS), and then 1:1 with either HbAo, HSA, or NSS. Only the Factor IX
      activity was significantly depressed by hemodilution (1/5 HbAo 50.20 +/- 8.11;
      HSA 61.05 +/- 6.72; NSS 74.75 +/- 9.83. 1/10 HbAo 46.50 +/- 5.57; HSA 64.97 +/-
      11.01; NSS 67.92 +/- 16.03). These results suggest that in-vitro hemodilution
      with HbAo causes a hypocoagulatory response through interference with Factor IX
      function.

PMID- 9167844
TI  - Enhancement of brain p0(2) during cardiopulmonary bypass using a hyperosmolar
      oxygen carrying solution.
AB  - During the past decade a new syndrome has been recognized: cerebral hypoxia
      secondary to cardiopulmonary bypass, resulting in impairment of cognitive memory.
      The incidence of the syndrome appears to be no less that 30% in patients over 65
      years of age undergoing cardiac surgery. There are several factors contributing
      to hypoxia produced by cardiopulmonary bypass. One of these factors is
      crystalloid pump prime and replacement solutions devoid of (1) oxygen carrying
      capacity and (2) devoid of protein and its colloid osmotic pressure. This
      shortcoming of cardiopulmonary crystalloid solutions is partially responsible for
      two of the three major pathologic effects of cardiopulmonary bypass: (1) hypoxia
      (2) interstitial fluid accumulation (anasarca, water-logging, edema). This report
      describes an oxygen carrying hyperosmolar solution which enhances brain p0(2) and
      diminishes interstitial fluid accumulation. This blood substitute consists of
      perfluorcarbons and saccharides, but could consist of a hemoglobin variant plus
      hyperosmolar ingredients other than saccharides. The advantage of a
      perfluorochemical is its ability to access small channels and to be centrifuged
      off the patient post-operatively with a cell saver. The advantage of saccharides
      is that they can be metabolized by the patient for energy, and they produce a
      moderate diuresis coming off bypass.

PMID- 9167846
TI  - Detection of residual polyethylene glycol derivatives in pyridoxylated-hemoglobin
      polyoxyethylene conjugate.
AB  - Purified hemoglobin solutions have been shown to cause renal toxicity in animals.
      Safe use of hemoglobin based therapeutics in humans requires modification of the
      hemoglobin molecule to prevent this toxicity. Hemoglobin modification may be
      accomplished by crosslinking the dimers within the hemoglobin tetramer or by
      derivatization of the alpha and/or beta subunits such that their size and/or
      charge prevents filtration by the glomeruli. Pyridoxylated hemoglobin
      polyoxyethylene conjugate (PHP) consists of hemoglobin molecules modified with
      alpha-carboxymethyl, omega-carboxymethoxy polyoxyethylene (POE). We have
      developed a high performance liquid chromatography-based (HPLC) method which can
      quantitate residual POE at levels of 0.1 mg/ml or greater. The detection of POE
      at this level of sensitivity requires the use of an evaporative light scattering
      detector (ELSD). A differential refractometer may also be used for POE detection,
      however the limit of quantitation for this detector is approximately 10 fold
      greater than that observed for the evaporative light scattering detector,
      resulting in a reduction in sensitivity. The successful use of this method
      requires sample deproteination using trichloroacetic acid. The reliability of the
      method has been demonstrated by spike recovery, precision, and reproducibility
      studies in PHP and buffer solutions.

PMID- 9167845
TI  - Introduction of negative charges to a crosslinked hemoglobin: lack of effect on
      plasma half time.
AB  - Intramolecularly crosslinked hemoglobins do not dissociate into alpha 1 beta 1
      dimers. As a result, they escape glomerular filtration and have plasma half times
      of 4 hours. This value is shorter than for albumin (5.2 hours) with similar
      molecular weight but higher negative charge. The present study was done to
      determine if increased negative charge on a hemoglobin covalently crosslinked
      with bis (3,5-dibromosalicyl) sebacate would lengthen its plasma half time.
      Negative charge was introduced by acylation with succinic anhydride. The product
      had a higher negative charge; however, plasma half time was not increased. A
      larger fraction of the succinylated material was excreted in the urine suggesting
      molecular instability.

PMID- 9167847
TI  - Novel fluorinated surfactants for perfluorochemical emulsification:
      biocompatibility assessments of glycosidic and polyol derivatives.
AB  - A novel series of fluoro-surfactants, derived from glycosides (monosaccharides)
      or polyols (ureas or carbamates), have been produced for use in respiratory gas
      carrying perfluorochemical emulsions. Compounds were synthesised via simple, but
      highly selective, routes using highly fluorinated isocyanates with amino
      alcohols, polyethoxylated alcohols and partially protected sugars at anomeric
      carbon; yields were 88-95%. Resultant compounds were perfluoroalkylated with
      hydroxylic "head" groups. The biocompatibility of surfactants with human blood in
      vitro was assessed using a conventional haemolysis test. Compounds showing
      insignificant haemolysis at up to 10 g l-1 were further evaluated (i) for their
      effects on neutrophil chemiluminescence, and (ii) in a human platelet aggregation
      assay. Some fluoro-surfactants inhibited spontaneous platelet aggregation, in
      blood anti-coagulated with hirudin, at concentrations of 0.01% (w/v), suggesting
      possible applications as antithrombotic agents.

PMID- 9167848
TI  - Oxalate excretion during the first 7 weeks in very-low-birth-weight infants.
AB  - To determine reference values, we studied urinary excretion of oxalate
      prospectively and longitudinally in a cohort of 23 very-low-birth-weight (VLBW)
      infants. The urinary oxalate concentrations were evaluated in 24-hour urine
      samples by the oxalate oxidase method. Urine samples were obtained at 1, 2-3, 4-5
      and 6-7 weeks of age. The median oxalate amount was 24 mumol/kg body weight/day
      with a 10th-90th percentile range of 16-45 in the 1st week. Oxalate excretion was
      highest in 2- to 3-week-old infants (median: 35; percentile range: 26-56 mumol/kg
      body weight/day). In the 4th-5th week, the median was 24 (percentile range: 15
      47) mumol/kg body weight/day and in weeks 6-7 also 24 (percentile range: 10-36)
      mumol/ kg body weight/day. Also, the urinary oxalate concentration as well as the
      oxalate-creatinine ratio showed increased values in the first 3 weeks of life and
      decreased values afterwards. In a multivariate analysis, nutrition or gestational
      age did not affect the urinary oxalate concentration, the daily amount excreted
      or the oxalate-creatinine ratio. The investigated parameters (oxalate amount and
      oxalate-creatinine ratio in urine) were significantly age dependent). The data
      show that urinary oxalate excretion in VLBW infants approaches levels that are in
      the same range as those of patients with urolithiasis. Thus the risk of
      nephrocalcinosis in VLBW infants may be increased.

PMID- 9167849
TI  - Rescue high frequency oscillatory ventilation for preterm infants:
      neurodevelopmental outcome and its prediction.
AB  - The role of rescue high-frequency oscillatory ventilation (HFO) in treating very
      low-birth-weight neonates with severe respiratory failure in relation to
      neurodevelopmental outcome has not been evaluated. We performed a retrospective
      cohort study on 21 patients (out of 52 consecutively admitted preterm neonates
      with gestational age < or = 30 weeks and birth weight < or = 1.250 g; mortality
      rate 60%) rescued with HFO between October 1988 and August 1993.
      Neurodevelopment, including Bayley Scales in Infant Development, was assessed at
      12-61 (mean 28.5) months adjusted age. Thirteen normal (scores better than 2 SD
      below mean, and no sensory or motor disability) (62%) and neurodevelopmentally
      disabled children (38%) survived more than 1 year for developmental assessment.
      The mental and performance developmental indices were 94 (78-117) and 89 (68
      110), and 63 (49-102) and 49 for the 13 normal and 8 disabled children,
      respectively (both p < 0.05). The incidence of bronchopulmonary dysplasia,
      intraventricular hemorrhage (IVH; grade 3 or 4), growth retardation,
      developmental scores and disabilities of these 21 HFO survivors were not
      significantly different from that of a birth-weight- and gestational-age-matched
      comparison group. While all HFO survivors had significant improvement in
      oxygenation 12 and 24 h after starting HFO, FiO2 and the alveolar-arterial oxygen
      gradient (A-aDO2) decreased significantly 1 h after starting HFO in survivors
      with normal neurodevelopmental outcome. The lack of initial response to HFO (20%
      decrease in A-aDO2 1 h after starting HFO) and the presence of grade 3 or 4 IVH
      predicted neurodevelopmental disability with a sensitivity of 63%, a specificity
      of 100%, and positive and negative predictive values of 100 and 81%,
      respectively. We concluded that HFO could be used as a rescue treatment in sick
      preterm neonates. The lack of early improvement in oxygenation and the presence
      of grade 3 or 4 IVH can predict adverse early childhood neurodevelopment in such
      neonates.

PMID- 9167850
TI  - Necrotizing enterocolitis in full-term or near-term infants: risk factors.
AB  - A retrospective case-control study of necrotizing enterocolitis (NEC) affecting
      infants weighing > 2,000 g at birth was performed to determine those factors
      which could contribute to the development of NEC. Twenty-four infants met the
      criteria of definite NEC. For each case the next 2 healthy newborns were matched
      as controls. When compared with the control group, NEC infants had a
      significantly higher frequency of prolonged rupture of membranes,
      chorioamnionitis, Apgar score < 7 at 1 and 5 min, respiratory problems,
      congenital heart disease, hypoglycemia, and exchange transfusions. Only 3 infants
      with NEC were healthy newborns with an unremarkable perinatal course before NEC.
      There were no differences in the frequency of preeclampsia, maternal diabetes,
      maternal drug abuse, meconium-stained amniotic fluid and polycythemia. These
      results indicate that most of these more mature infants have a predisposing
      factor before developing NEC.

PMID- 9167851
TI  - Assessment of perinatal pathologies in premature neonates using a syllable
      discrimination task.
AB  - In order to assess whether neonatal complications have any impact on early
      cognitive capacities, premature neonates between 35 and 36 weeks of gestation
      were tested in a syllable discrimination task using a non-nutritive sucking
      paradigm. The sucking response to a change of syllable was negatively correlated
      with the presence of brain lesions. In contrast to full-term and healthy
      premature neonates, who increase their sucking rates after a change of syllable,
      premature neonates with subcortical lesions react to a syllable change by
      exhibiting lower sucking rates relative to a no-change situation. This behavior
      may tentatively be related to a contingency learning deficit, secondary to
      subcortical lesions involving in particular the caudate nucleus.

PMID- 9167852
TI  - Effects of 8-epi-prostaglandin F2 alpha and U46,619 on pulmonary hemodynamics in
      piglets.
AB  - Non-cyclooxygenase-derived prostaglandin F2- (PGF2)-like compounds can be formed
      by membrane lipid peroxidation. We sought to characterize one member of this
      class of compounds, 8-epi-PGF2 alpha, for its biological properties on the
      pulmonary vasculature in young piglets. We first compared 8-epi-PGF2 alpha to a
      thromboxane (Tx) mimetic, U46,619, to determine relative pulmonary
      vasoconstrictive effects. We next determined if the vasoconstriction induced by
      both agonists would be reversed by 50 ppm of inhaled nitric oxide (NO). We also
      determined the degree of inhibition of U46,619 and of 8-epi-PGF2 alpha by a Tx
      receptor antagonist, SQ 30,741. Anesthetized, ventilated piglets (18 +/- 2 days,
      3.7 +/- 0.5 kg) were infused with randomly selected doses of U46,619 and of 8-epi
      PGF2 alpha to describe dose-response curves plotting pulmonary vascular
      resistance (PVRi) against dose. When a maximal dose was achieved, inhaled NO (50
      ppm) was administered. Results for the calculated PVRi (mm Hg/l/ min/kg) are as
      follows (mean +/- SD): for U46,619, baseline value: 43 +/- 10, peak dose: 165 +/-
      46, and peak dose with NO: 73 +/- 33; for 8-epi-PGF2 alpha, baseline value: 38 +/
      9, peak dose: 138 +/- 30, and peak dose with NO: 72 +/- 25, and for both drugs,
      PVRi at peak dose was greater than at baseline (p < 0.001). PVRi at peak dose
      plus NO also remained elevated above baseline (p < 0.05; repeated measures
      ANOVA). The Tx receptor antagonist SQ 30,741 (1-10 mg/kg) inhibited U46,619
      induced pulmonary vasoconstriction completely; however, the 1 mg/kg dose provided
      only 90% inhibition against 8-epi-PGF2 alpha. We conclude that 8-epi-PGF2 alpha
      can contribute to pulmonary vasoconstriction in young piglets in a dose-dependent
      reversible manner and that it acts primarily via pulmonary vascular Tx receptors.

PMID- 9167853
TI  - Growth and development of the exocrine pancreas in newborn pigs: the effect of
      colostrum feeding.
AB  - This study examined the growth and development of the pancreas in naturally
      suckled piglets during the first 3 postnatal days and the effects of colostrum
      feeding on the pancreatic development. The results showed that in naturally
      suckled piglets, the absolute weight of the pancreas increased 51% during the
      first day and 86% by the 3rd day, and the relative weight per unit body weight
      increased 37% during the first day and 47% by the 3rd day. Associated with the
      rapid weight gain was a significant increase in pancreatic DNA content and
      enlargement of pancreatic exocrine acinar units, the latter apparently resulted
      from an increase in number rather than size of acinar cells. It was further shown
      that the rapid pancreatic growth was related to colostrum ingestion as
      significant pancreatic weight gain was observed in piglets bottle-fed porcine
      colostrum or trypsinized porcine colostrum but not in piglets bottle-fed 5%
      lactose solution. Trypsinized porcine colostrum was apparently more potent than
      native porcine colostrum in stimulating pancreatic growth in newborn pigs. It is
      speculated that colostrum-borne growth factors and/or postnatal surge of gut
      hormones following onset of oral feeding are the major factors responsible for
      the rapid postnatal pancreatic growth in newborns.

PMID- 9167854
TI  - Surfactant protein-B and lung function in surfactant-treated preterm lambs.
AB  - We asked if the amount of SP-B (range 37-410 micrograms/ml) in surfactants used
      to treat preterm lambs at 123 days of gestation correlated with postnatal lung
      function or the SP-B content of surfactant recovered by alveolar washes after 10
      h ventilation. Ventilation was initiated using a low tidal volume strategy to
      minimize early lung injury. There were small increases in compliance for the
      lambs treated with surfactants containing more than 37 micrograms/ml SP-B and an
      increased lung volume for lambs treated with a surfactant containing 385
      micrograms/ml/ml relative to the surfactant containing 37 micrograms/ml SP-B. The
      amount of SP-B in the surfactant used for treatment correlated linearly with the
      amount of SP-B in the surfactant recovered from the lambs (r = 0.95, p < 0.001).
      Albumin leak from the vasculature to the airspace was low as was total protein in
      alveolar washes, indicating minimal lung injury. The SP-B content of surfactant
      (from 37 to 410 micrograms/ml) had minimal effects on postnatal lung function
      over a 10-hour study period in lambs ventilated in a manner to minimize lung
      injury.

PMID- 9167855
TI  - Evaluation of potentially injurious effects of exogenous surfactant
      lysophospholipids on the alveolar epithelium and pulmonary mechanics.
AB  - Although lysophospholipids are normally found in the lung and their presence is
      connected to the metabolic pathway of surfactant phospholipids, several studies
      have reported that their intratracheal instillation is able to induce severe
      alveolar epithelial injury. Since lysophospholipids are normally present in
      exogenous surfactants as a consequence of the nonenzymatic hydrolysis of parent
      phospholipids during their production and shelf-life, the aim of this study was
      to test the potential toxicity of surfactant lysophospholipids in artificially
      ventilated newborn rabbits in comparison with that of pure
      lysophosphatidylcholine (Lyso-PC) suspensions. In premature (surfactant
      deficient) animals, a commercially available Curosurf batch (0.56 mg Lyso-PC/ml)
      improved lung-thorax compliance and reduced lactate dehydrogenase (LDH), total
      protein and hemoglobin contents in bronchoalveolar lavage (BAL) fluid. The same
      batch submitted to thermal stress in order to increase the Lyso-PC content (10.2
      mg Lyso-PC/ml) failed to improve lung mechanics but did not induce any
      significant change in biochemical markers in BAL fluid. When suspended in saline,
      pure Lyso-PC had a dramatic and dose-dependent tissue-damaging effect with
      increased LDH, hemoglobin and protein contents in BAL and a fall in the
      lungthorax compliance, in both immature and mature (near-term) animals. The lack
      of toxicity of Lyso-PC in Curosurf might be explained by an interaction with
      surfactant phospholipids.

PMID- 9167856
TI  - The functional anatomy of the ciliary muscle in four avian species.
AB  - The functional anatomy of avian ciliary muscles has been difficult to describe,
      due to the muscle's inaccessible location inside the eye. The ciliary muscle of
      the chicken (Gallus gallus domesticus), the pigeon (Columbia livia), the kestrel
      (Falco sparverius) and the hooded merganser (Margus cucullatus) (four species
      with differing accommodative needs) was examined histologically in both the
      relaxed and contracted states. The ciliary muscle of all four species can be
      divided into three main muscle fibre groups based on insertion and origin:
      anterior, posterior and internal. The anterior muscle fibre group originates at
      the sclera under the scleral ossicles and inserts into the inner lamellae of the
      cornea. During accommodation these fibres pull the cornea posteriorly, changing
      the curvature of the cornea. The posterior muscle fibre group originates on the
      sclera and inserts posteriorly onto the baseplate of the ciliary body. The
      posterior fibre group acts on the baseplate of the ciliary body, pulling it
      forward to change the curvature of the lens during accommodation. The internal
      muscle fibre group extends from the baseplate of the ciliary body to the inner
      lamellae of the cornea and thus has a role in both corneal and lenticular
      accommodation. Species differences do exist, as seen in subgroups determined by
      the orientation of the fibres between the relaxed and contracted states and the
      percentage of fibres within the main muscle fibre groups. In general, the
      majority of ciliary muscle fibres in chickens, pigeons, and kestrels are in the
      anterior muscle fibre group, suggesting an emphasis on corneal accommodation; in
      the ciliary muscle of the hooded merganser, the majority of fibres are in the
      internal and posterior muscle fibre groups, indicating that lenticular
      accommodation is the predominant form of accommodation.

PMID- 9167857
TI  - Temporal filtering properties of ampullary electrosensory neurons in the torus
      semicircularis of Eigenmannia: evolutionary and computational implications.
AB  - Weakly electric fish have parallel electrosensory systems, the phylogenetically
      older ampullary system and the novel tuberous system. The tuberous system is an
      adaptation related to the evolution of active electrolocation. To examine the
      evolutionary relationship of the ampullary and tuberous systems, the temporal
      filtering properties of ampullary neurons in the dorsal torus semicircularis of
      Eigenmannia were studied. 'Whole-cell' recordings were made in vivo using patch
      type pipettes. The responses of 19 neurons to sinusoidal electric signals (< 40
      Hz) were recorded and the anatomy of these neurons demonstrated by injection of
      biocytin. All eight low-pass ampullary neurons had broad, relatively smooth post
      synaptic potentials (psps) that at low frequencies nicely reflected the
      sinusoidal stimuli. These neurons had somata of 10-14 microns diameter and thick,
      spiny dendrites. Eight high-pass neurons were recorded, representing three
      physiological classes. The first class (3 neurons) had psps that roughly followed
      the sinusoidal time course of the stimulus; the psp morphology was similar to low
      pass neurons. The second class had many small, fast, individual psps; their rate
      of occurrence varied with the stimulus. Finally, four neurons showed psps that
      were of constant width across stimulus frequencies. All three classes of high
      pass neurons had small somata (8-10 microns diameter) with thin dendrites and
      either few or no spines. Some of these neurons had large varicosities on the
      dendrites. Three neurons had band-pass filtering properties: neurons that showed
      strong band-pass properties were morphologically similar to low-pass neurons.
      Comparisons of the temporal filtering, shapes of post-synaptic potentials, and
      anatomy of ampullary and tuberous neurons in the torus suggest that the circuitry
      for tuberous processing in the torus may have evolved as an elaboration or
      duplication of the ampullary system. The mechanisms underlying the low-pass
      filtering characteristics of tuberous neurons therefore appear to have predated
      the evolution of the tuberous system and to have served as a pre-adaptation for
      the evolution of the jamming avoidance response. In addition, these data support
      the hypothesis that spine density influences the temporal filtering properties of
      neurons.

PMID- 9167858
TI  - Molecular insights into the phylogeny of mormyriform fishes and the evolution of
      their electric organs.
AB  - In this report we generate a partial phylogeny of the mormyriform fishes using
      mitochondrial DNA sequences from twelve species of mormyriforms belonging to five
      genera. Electric organs and electric organ discharges are also examined. We have
      sequenced and aligned 373 bases from the mitochondrial 12S rRNA and 559 bases
      from the 16s rRNA from fourteen species of the superorder Osteoglossomorpha. Two
      non-mormyriform genera were used as outgroups. Three phylogenetic methods
      generated concordant partial phylogenies for these fish. Our analysis focuses on
      the genus Brienomyrus, which is a heterogeneous clade with at least eleven
      nominal species. Six morphs from Gabon had distinctive EODs but were
      morphologically 'cryptic' in that they all had the brachyistius-like body
      morphology. DNA analysis fully supports the EOD data that the six morphs
      represent distinct clades. The group from Gabon is monophyletic, while B.
      brachyistius from West Africa is a separate lineage. B. niger, a second distinct
      lineage, is a sister group to the six species from Gabon. Petrocephalus is the
      sister group of all the genera of the subfamily Mormyrinae so far analyzed,
      thereby confirming previous osteological results. Gymnarchus niloticus is the
      sister group of the family Mormyridae, also confirming an earlier phylogenetic
      hypothesis based on morphology. The molecular data adds polarity to electric
      organ characteristics. Stalkless electrocytes appear to be primitive.
      Petrocephalus, with non-penetrating stalked electrocytes innervated on the
      posterior side, represents an ancestral state for the Mormyridae, while
      Marcusenius. Brienomyrus and Gnathonemus with penetrating-stalked electrocytes,
      represent the apomorphic condition. Two species with doubly-penetrating
      electrocytes innervated on the posterior side may represent a transitional stage.
      At least two species of Brienomyrus appear to have reverted to non-penetrating
      stalked electrocytes, possibly through paedomorphosis.

PMID- 9167859
TI  - Mild head injury: neuropathology, sequelae, measurement and recovery.
AB  - Head injuries are common in industrialized countries and the majority of them are
      defined as 'minor' or 'mild' injuries (MHI). These terms, however, can be
      misleading because the sequelae that often follow such injuries can cause
      significant detriment to psychosocial and interpersonal functioning Clinical
      psychologists in most areas of specialism are likely to encounter MHI because of
      their high frequency and the types of problems they can cause. An overview of the
      body of knowledge on this subject is therefore of some importance. This paper
      reviews the literature concerning the neuropathology, measurement, sequelae and
      recovery of MHI. The following subjects are addressed: (i) the relationship
      between the neuropathology of severe head injury and the neuropathology of MHI;
      (ii) the limitations of traditional measures of head injury severity (e.g. post
      traumatic amnesia) when applied to MHI; (iii) factors relevant to the recovery of
      post-concussion symptoms following MHI; and (iv) intervention and treatment
      following MHI.

PMID- 9167860
TI  - Does victimization account for sex differences in depressive symptoms?
AB  - Women are more depressed than men, and more frequently victimized. We explored
      the possibility that childhood sexual abuse (CSA) and adult victimization account
      for the higher levels of depression in women. Depressive symptoms and
      victimization histories were compared in a sample of 91 men and 76 women seeking
      out-patient psychotherapy. The women were more depressed, and more likely to have
      a history of CSA than the men. CSA accounted for a significant proportion of the
      sex difference in depression levels. The women also were more likely to have been
      victimized as adults than were the men. However, adult victimization was not
      associated with higher depression levels, and, therefore, did not account further
      for the sex difference.

PMID- 9167861
TI  - Lifetime episodes of dysphoria: gender, early childhood loss and personality.
AB  - The roles of gender, early childhood loss and personality as risk factors for
      lifetime episodes of dysphoria were examined in a large sample of college
      students (N = 557). Dysphoria classifications were based on the Inventory to
      Diagnose Depression (IDD) and the IDD-Lifetime Version. Brief dysphoria was
      defined as meeting DSM-III-R symptom criteria for major depression without
      meeting the two-week duration criteria, whereas protracted dysphoria required
      that the duration criteria were also met. Although females reported higher levels
      of depressive symptoms and neuroticism than did males, and were more likely to
      have a lifetime history of episodes of dysphoria, males were more susceptible to
      the adverse effects of early childhood loss. Males with loss were more likely to
      have a history of protracted dysphoria and to report higher levels of neuroticism
      than were males who did not experience an early parental loss. Neuroticism, in
      turn, acted as a trait vulnerability characteristic to episodes of dysphoria in
      both males and females. Interestingly, the effects of gender on lifetime
      experience of dysphoria were mediated by neuroticism: females' increased
      vulnerability to episodes of dysphoria was due to their elevated levels of
      neuroticism.

PMID- 9167862
TI  - Eye-movements and visual imagery: a working memory approach to the treatment of
      post-traumatic stress disorder.
AB  - It has been claimed that the symptoms of post-traumatic stress disorder (PTSD)
      can be ameliorated by eye-movement desensitization-reprocessing therapy (EMD-R),
      a procedure that involves the individual making saccadic eye-movements while
      imagining the traumatic event. We hypothesized that these eye-movements reduce
      the vividness of distressing images by disrupting the function of the
      visuospatial sketchpad (VSSP) of working memory, and that by doing so they reduce
      the intensity of the emotion associated with the image. This hypothesis was
      tested by asking non-PTSD participants to form images of neutral and negative
      pictures under dual task conditions. Their images were less vivid with concurrent
      eye-movements and with a concurrent spatial tapping task that did not involve eye
      movements. In the first three experiments, these secondary tasks did not
      consistently affect participants' emotional responses to the images. However,
      Expt 4 used personal recollections as stimuli for the imagery task, and
      demonstrated a significant reduction in emotional response under the same dual
      task conditions. These results suggest that, if EMD-R works, it does so by
      reducing the vividness and emotiveness of traumatic images via the VSSP of
      working memory. Other visuospatial tasks may also be of therapeutic value.

PMID- 9167863
TI  - The effect of one-session treatment for spider phobia on attentional bias and
      beliefs.
AB  - Spider phobics were tested before and after one-session treatment for spider
      phobia, or a comparable waiting period, using a spider-word Stroop test and
      questionnaires in which they rated spider-relevant threat beliefs. Compared with
      untreated spider phobic controls, the treated phobics changed significantly in
      their negative beliefs about spiders after treatment. Controls and treated
      phobics showed the same change in their reaction time latencies to spider stimuli
      in the Stroop test. These data are consistent with the hypothesis that the
      modification of threat beliefs is crucial in changing the response to phobic
      stimuli. It is concluded that the threat-specific Stroop test is an ambiguous
      measure of fear-related cognitive processes.

PMID- 9167864
TI  - Normal and abnormal reasoning in people with delusions.
AB  - People who experience delusions have been found to request less information prior
      to making a decision than control participants on tasks that are unrelated to the
      theme of the delusion (Huq, Garety & Hemsley, 1988). Two studies investigated
      whether people with delusions have an absolute deficit in reasoning or a more
      specific data-gathering bias. In Expt 1, 12 people with delusions, 12 people with
      depression and 12 normal controls were shown the results of spinning a supposedly
      biased coin. The evidence provided varied in the number of heads to tails. In
      normal controls a high ratio of head to tails produces a high estimate that the
      coin is biased. In this experiment, where the evidence gathered was predetermined
      by the experimenter, all groups of participants were shown to reason in a similar
      way. Experiment 2 tested whether a difference would exist between the groups in
      conditions where participants were free to determine the amount of evidence seen,
      in contrast to when all of them viewed the same evidence. Two jars of beads in
      opposite but equal ratios (e.g. 85:15, 15:85) were shown to 15 people with
      delusions, 15 with depression and 15 normal controls. On the basis of beads being
      drawn one at a time, it was the participants' task to determine which jar they
      came from. When free to decide when they wished, people with delusions decided on
      the basis of less evidence than the other groups. However, as in Expt 1, the
      group with delusions did not differ when made to view the same amount of beads as
      other participants. Therefore, people with delusions have a data-gathering bias
      rather than a difficulty in employing the data in reasoning. This "jump to
      conclusions' bias generalized to a less discriminable ratio of beads (60:40), and
      was not a consequence of impulsiveness or memory deficit.

PMID- 9167865
TI  - Coping with hallucinations: exploring stress and coping framework.
AB  - This study explored application of the theoretical framework of Lazarus & Folkman
      (1984) to coping with hallucinations in schizophrenia. Eighty-one patients were
      interviewed with a structured schedule. Unprompted reports of coping indicated
      wide use of both 'hallucination-specific' and 'general' strategies. Factor
      analysis of a coping checklist produced three factors which were utilized in
      regression analyses. The active acceptance factor may relate to control of
      hallucinations, the passive coping factor predicted distress reduction but,
      surprisingly, the resistance coping factor, which contained hallucination
      specific coping strategies, predicted poor distress reduction. Clinical and
      research implications are noted.

PMID- 9167866
TI  - The influence of methodological differences on the outcome of body size
      estimation studies in anorexia nervosa.
AB  - A major problem that has dogged research into body image disturbance in anorexia
      nervosa concerns the diversity of measurement procedures employed in studies of
      body size estimation. Many researchers believe that results obtained with
      different procedures cannot meaningfully be compared with each other, because the
      methods used measure different aspects of the body image. A meta-analysis of 33
      body size estimation studies was conducted to investigate whether methodological
      differences do indeed influence outcome. This analysis revealed a general
      overestimation of body size among anorexia patients. Although a difference in
      mean effect size was found between studies using Body Part and Whole Body
      methods, this difference was absent when only the most commonly used Body Part
      method, the visual size estimation procedure, was considered. Among Whole Body
      methods, silhouette methods could not be distinguished from the rest in terms of
      effect size. It was concluded that Whole Body methods and the visual size
      estimation procedure assess correlated aspects of the body image.

PMID- 9167867
TI  - Selective processing of three types of stimuli in eating disorders.
AB  - A modified version of the Stroop colour naming task was administered to patients
      with anorexia nervosa, patients with bulimia nervosa and a control group. Stimuli
      were separated into three areas of concern. Compared to the controls, both
      patient groups showed selective processing of information related to eating and
      weight. Patients with anorexia nervosa also showed selective processing of
      information related to shape. There were no differences between the two patient
      groups.

PMID- 9167868
TI  - Factorial structure of the Wisconsin Card Sorting Test.
AB  - This study examined the factorial structure of the Wisconsin Card Sorting Test
      (WCST) in normal university students (N = 135) and a mixed clinical sample (N =
      139). Two highly stable orthogonal factors were observed accounting for 70 and 21
      per cent of the variance, respectively. Factor I was interpreted as reflecting
      undifferentiated executive function while Factor II may measure cognitive
      abilities associated with attentional function. This work can serve as the basis
      for further examination of the construct validity of the WCST and has
      implications for its use.

PMID- 9167870
TI  - Reducing stereotyped behaviour: a comparison of two methods of programming
      differential reinforcement.
AB  - Differential Reinforcement of Other behaviours (DRO) has proven to be successful
      in reducing challenging behaviour, although the need for staff vigilance can
      limit its applicability in applied settings. The present study compared the
      effectiveness of whole-interval DRO with momentary DRO, a less intensive
      schedule. In a multiple-baseline design, two participants who exhibited high-rate
      stereotyped behaviours were presented with the two schedules. Momentary DRO was
      more effective than whole-interval DRO in reducing the targeted stereotypies of
      one participant, and as effective with the second. Momentary DRO was also more
      effective in reducing a second (non-consequated) stereotyped behaviour.

PMID- 9167869
TI  - Single case evaluation of the effects of aromatherapy and massage on disturbed
      behaviour in severe dementia.
AB  - Aromatherapy and massage could provide a useful addition to psychological
      therapeutic interventions with clients suffering from dementia. The effects of
      aromatherapy and massage on disturbed behaviour in four individuals with severe
      dementia were evaluated using a single-case research design. Each participant
      received 10 treatment sessions of aromatherapy, aromatherapy and massage
      combined, and massage alone. The effects on each individual's behaviour in the
      hour following treatment were assessed against 10 'no treatment' control
      sessions. Reliable individualized disturbed behaviour scales were designed. The
      effects of the treatments were mixed. The opinion of the staff providing
      treatment was that all participants benefited. On close scrutiny, only one of the
      participants benefited from the aromatherapy and massage to a degree that reached
      statistical significance. In two of the cases aromatherapy and massage led to an
      increase in agitated behaviour. The importance of the single case study approach
      with this client group is discussed.

PMID- 9167872
TI  - Clinical judgment and case formulation.

PMID- 9167871
TI  - A note of caution for clinicians using the Paced Auditory Serial Addition Task.
AB  - In this study, a group of 30 university students were administered the Paced
      Auditory Serial Addition Task (PASAT) and their performance compared with that of
      an older group matched for ability on the National Adult Reading Test (NART).
      They were also compared on measures of memory (forwards and backwards digit span)
      and a timed visual search task. The younger participants showed significantly
      inferior performance on the PASAT. This is counter-intuitive considering that the
      test is viewed primarily as a measure of speed of processing. There were no
      differences on measures of short-term memory, but the older participants found
      fewer targets on the visual search task. The implications of this result for
      clinicians using the PASAT are discussed.

PMID- 9167873
TI  - Extra label drug use.

PMID- 9167874
TI  - Crisis in our midst.

PMID- 9167875
TI  - An ethicist's commentary on the case of the anorexic client who does not feed her
      dog.

PMID- 9167876
TI  - The Canadian Cooperative Wildlife Health Centre and surveillance of wild animal
      diseases in Canada.
AB  - The Canadian Cooperative Wildlife Health Centre (CCWHC) was established in 1992
      as an organization among Canada's 4 veterinary colleges, with a mandate to apply
      veterinary medicine to wildlife management and conservation in Canada. A major
      function of the CCWHC is nation-wide surveillance of wild animal diseases.
      Disease surveillance is conceived as consisting of 4 different activities:
      detection, diagnosis, information management, and use of information. In the
      CCWHC surveillance program, detection of disease is carried out by a wide range
      of professional and avocational field personnel, and much effort is expended to
      stimulate and support this activity. Diagnosis is done by personnel of provincial
      and federal veterinary laboratories and the CCWHC. Information management is
      achieved through a national database of wildlife disease incidents developed and
      maintained by the CCWHC. Use of information is enabled through established
      channels for distribution of information derived from the surveillance program to
      persons responsible for wildlife programs and policies, and to the public. There
      has been a high demand for the services of the CCWHC since its establishment. The
      CCWHC responds to approximately 2000 requests for information annually,
      distributes its newsletter to over 1700 recipients, examines approximately 1200
      wild animal submissions each year, and has accumulated records of over 5000
      disease incidents in its database. Technical information from the CCWHC has
      benefited federal, provincial/territorial, and nongovernment wildlife agencies;
      endangered species recovery programs; federal and provincial veterinary services;
      and federal and provincial public health programs.

PMID- 9167877
TI  - Comparison of unilateral arytenoid lateralization and ventral
      ventriculocordectomy for the treatment of experimentally induced laryngeal
      paralysis in dogs.
AB  - This study evaluated changes in respiratory function in dogs with experimentally
      induced laryngeal paralysis treated with either unilateral arytenoid
      lateralization or ventral ventriculocordectomy, and compared the effectiveness of
      these procedures. Evaluation consisted of clinical assessment and tidal breathing
      flow volume loop and upper airway resistance measurements. Carbon dioxide and
      doxapram hydrochloride were used as respiratory stimulants. Initially, all dogs
      improved clinically after corrective surgery. However, by the end of the study,
      laryngeal collapse had developed in 2 of 5 dogs corrected by ventral
      ventriculocordectomy. No statistical differences in upper airway mechanics
      testing were seen between the surgical procedures. With both groups combined,
      many measurements of upper airway obstruction improved after surgical correction.
      Based on this study, these surgical procedures yield comparable results, although
      additional studies are needed to evaluate both the cause of laryngeal collapse
      and the role of upper airway mechanics testing in the evaluation of canine
      laryngeal paralysis.

PMID- 9167878
TI  - Repair of a deep digital tendon deficit in a horse using a polypropylene implant.
AB  - A yearling horse was treated for a chronic wound with a 4 cm deficit in the deep
      digital tendon. The gap in the tendon was bridged with paired polypropylene
      braided implants designed for use as a ligament augmentation device.
      Uncomplicated healing and return to function occurred.

PMID- 9167879
TI  - Prevention of hypothermia in cats during routine oral hygiene procedures.
AB  - While thermally supported cats experienced a drop in body temperature during
      dental procedures, the drop was significantly greater in cats without thermal
      support. As cats are at risk of developing clinical hypothermia during dental
      procedures, steps should be taken to minimize the loss of body heat.

PMID- 9167880
TI  - Central nervous system and vertebral malformation resembling the Arnold-Chiari
      syndrome in a Simmental calf.
AB  - Multiple congenital anomalies were identified in a stillborn calf, including
      severe cerebellar hypoplasia and central nervous system abnormalities resembling
      the Arnold-Chiari syndrome of malformation of calves. The Arnold-Chiari
      malformation occurs sporadically and has little economic impact, whereas
      cerebellar hypoplasia implies the presence of BVD virus in the herd.

PMID- 9167881
TI  - Distribution of Streptococcus suis capsular types in 1996.

PMID- 9167882
TI  - The obstructive bowel pattern: an inconsistent radiographic sign of obstruction.

PMID- 9167883
TI  - Malassezia dermatitis.

PMID- 9167884
TI  - Relationship between free-running period and minimum tolerable light pulse
      interval of skeleton photoperiods in field mice Mus booduga.
AB  - The entrainment of the circadian rhythm of locomotor activity was studied in the
      field mouse Mus booduga in order to examine the relationship between the free
      running period (tau) and minimum tolerable light pulse interval of the skeleton
      photoperiods. The animals were entrained under three different light/dark (LD)
      schedules, each out of phase with the other. They were then subjected to various
      skeleton photoperiods created by two repeated light pulses (LPs) interrupting
      darkness. Animals that selected the shorter interval between the LPs as their
      "subjective night" had significantly shorter tau (23.13 +/- 0.38 h) as compared
      to those that selected the longer dark interval as subjective night (tau = 23.87
      +/- 0.18 h). When the longer dark interval was 12 h, animals selecting that
      interval as their subjective night included both long-tau and short-tau
      individuals. When both intervals of darkness were of equal duration, no
      difference in the selection of subjective night was seen between short and long
      tau animals. When the "dusk" LP for the animals that selected the longer dark
      interval as subjective night was advanced by 2 h to create a new skeleton
      photoperiod, the number of transient cycles appearing before steady-state
      entrainment was found to depend on the duration of the photoperiods. When the
      night defined by the two LPs was reduced below 6h, a dramatic "phase jump" in the
      activity rhythm was observed, and the initial phase relationship was restored
      after a relaxation in the night duration. We observed considerable
      interindividual variation in the "minimum tolerable light pulse interval of
      skeleton photoperiods," which we suggest may be due to the observed variation in
      tau among individuals.

PMID- 9167885
TI  - Description of the photoperiodic control of larval burrowing in the blowfly
      Lucilia cuprina: a novel index for photoperiodic research.
AB  - The photoperiodic control of larval burrowing depth in the Australian sheep
      blowfly Lucilia cuprina (Wiedemann) (Diptera: Calliphoridae) was investigated by
      measuring burrowing depth under controlled laboratory photoperiods. The results
      demonstrated that larvae exposed to long photoperiods (LD 18 : 6) burrowed to
      deeper depths than those in shorter photoperiods (LD 12 : 12), and that this
      behavior was induced during the third instar stage. The ecological significance
      of this behavior is discussed, as are the ways in which daylength is measured and
      depth assessed. The use of burrowing depth could prove to be a novel index of a
      photoperiodic response and provide a far simpler approach to the study of
      photoperiodism in certain insect species.

PMID- 9167886
TI  - Twenty-four-hour rhythms of serum ACTH, prolactin, growth hormone, and thyroid
      stimulating hormone, and of median-eminence norepinephrine, dopamine, and
      serotonin, in rats injected with Freund's adjuvant.
AB  - The effect of Freund's adjuvant injection on 24-h variation of circulating ACTH,
      prolactin, growth hormone (GH), and thyroid-stimulating hormone (TSH) levels, and
      of norepinephrine (NE) content, and dopamine (DA) and serotonin (5HT) turnover in
      median eminence, was examined in adult rats kept under light between 0800 and
      2000 h daily. Groups of 6-10 animals received Freund's complete adjuvant or its
      vehicle at 1100 h 3 days before sacrifice and were killed by decapitation at six
      different time intervals throughout a 24-h cycle. In rats injected with
      adjuvant's vehicle, serum ACTH and prolactin exhibited peak values around the
      light-dark transition (p < 0.0001 and < 0.04, respectively), while the maximum in
      TSH was found in the late afternoon (p < 0.0001, one-way ANOVA). GH levels did
      not vary on a 24-h basis. In Freund's adjuvant-injected rats, 24-h variations of
      TSH levels became blunted, while 24-h variations of prolactin and ACTH persisted.
      Freund's adjuvant augmented serum ACTH and prolactin levels, and decreased GH and
      TSH levels (p < 0.0007, factorial ANOVA). Median-eminence NE content, and
      turnover of DA, assessed by measuring dihydroxyphenylacetic acid, DOPAC/DA ratio,
      and of 5HT, assessed by measuring 5-hydroxyindoleacetic acid, HIAA/5HT ratio,
      varied on a 24-h basis in rats receiving adjuvant's vehicle (p < 0.02). Median
      eminence NE content attained its maximum at 1600-2000 h, while maxima in DOPA/DA
      and HIAA/5HT ratios occurred at 0400 h. Injection with Freund's adjuvant reduced
      the amplitude of the daily variation of NE content, shifted the maximum of
      DOPAC/DA ratio toward the light-dark transition, and blunted the daily variation
      in HIAA/5HT ratio in median eminence. The administration at 1200 of the
      immunosuppressant drug cyclosporine (5 mg/kg, 5 days) restored the augmented ACTH
      and prolactin levels (p < 0.0001, factorial ANOVA) and depressed GH and TSH
      levels (p < 0.02) found in Freund's adjuvant-injected rats. Cyclosporine was also
      effective in restoring 24-h rhythmicity of serum ACTH and TSH, but not of
      prolactin, levels. Cyclosporine did not modify the effect of Freund's adjuvant on
      time-of-day changes of median-eminence NE content, but it was effective in
      counteracting the changes of DA and 5HT turnover found after immunization. The
      results are compatible with a significant effect of immune-mediated inflammatory
      response at an early phase after Freund's adjuvant injection on ACTH, GH,
      prolactin, and TSH release, which is partially sensitive to immunosuppression by
      cyclosporine.

PMID- 9167887
TI  - Circadian rhythm in the hypothermic response to serotonin1A receptor agonist 8-OH
      DPAT in rats.
AB  - In a recent study, we found a circadian rhythm in the serotonin (5-HT) syndrome
      (forepaw treading, head weaving, and flat body posture) in the response to the 5
      HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The
      present study examined the rhythm in the responsiveness to 8-OH-DPAT by observing
      hypothermia, another index of the 5-HT1A receptor function. Rats standardized to
      L(1800-0600) : D(0600-1800) were subcutaneously administered with 0.16 mg/kg 8-OH
      DPAT at one of the following times of day: 00:00, 04:00, 08:00, 12:00, 16:00,
      20:00 h. Two parameters of assessing the hypothermic response, the maximum
      decrease in temperature after the administration (MAXDT) and the area under the
      curve of the decrease in temperature (AUCDT), displayed significant circadian
      rhythms with the peaks in the middark phase (12:00 h). The waveform of the
      rhythms observed was similar to that of the rhythms that we observed previously
      in the 5-HT syndrome. The evidence presented here further supports that the
      central postsynaptic 5-HT1A receptor function exhibits a circadian rhythm.

PMID- 9167889
TI  - Circadian rhythm in the torque developed by elbow flexors during isometric
      contraction. Effect of sampling schedules.
AB  - Time-dependent changes in elbow flexion torque have been documented according to
      two different sampling schedules. Seven physical education students took part in
      the first series of experiments, and 7 other similar subjects in the second. In
      both sets of experiments, the subjects performed isometric contractions: maximal
      and submaximal at 90 degrees in the first experiments and maximal at different
      angular positions in the second. After a 30-minute rest period, the torque
      developed was measured at 00:00, 06:00, 09:00, 12:00, 15:00, 18:00, and 21:00 h
      on the day of the experiment. These subjects remained in the laboratory for 24 h.
      In the second series of experiments, the torque developed was measured at 01:00,
      05:00, 09:00, 13:00, 17:00, and 21:00 h over the subsequent 6 days with only one
      test session per day. In this case, there was an interval of 20 h between two
      successive test sessions. In the first experiment, a significant time-of-day
      effect was observed for the torque of the elbow flexors under isometric
      conditions with an acrophase at 17:58 h. The 24 h normalized mean score was
      92.85% with an amplitude of 7.63% of the daily mean. In the second series of
      experiments, there was evidence of a circadian rhythm in the torque developed by
      the elbow flexors at every angle position, especially at 90 degrees, the angle
      investigated in the first set of experiments. The peak torque was calculated to
      have occurred at 17:55 h. The amplitude of the rhythm was equal to 6.99% of the
      daily mean. There were no statistically significant differences in the
      characteristics of the circadian rhythm observed between the two experimental
      designs. We concluded that an experiment extending over several days could be
      employed to evaluate circadian rhythms in muscular activity reliably.

PMID- 9167890
TI  - Differences over the life span in daily life-style regularity.
AB  - A diary-based instrument-the Social Rhythm Metric (SRM)-was used to assess the
      level of stability of daily social and behavioral rhythms in a group of 239
      healthy subjects (112 male, 127 female) ranging in age from 20 to 89 years. Each
      subject completed the instrument for two consecutive weeks, which were averaged
      to yield one measure (SRM score) of life-style regularity [range 0 (least
      regular) to 7 (most regular)] and another of activity level index (ALI),
      corresponding to the number of (diary listed) activities done per week (max. =
      119). SRM score increased reliably with age group at an average rate of 0.018
      units per year. ALI showed an "inverted U"-shaped function with a maximum at
      about 50 years. SRM changes appeared not to be related to demographic differences
      between the age groups, although ALI differences may have been so related. No
      main effects or interactions were found with gender. Life-style regularity
      appears to increase over the life span in response to both biological and
      psychosocial changes and may represent an adaptation to age-related changes in
      the circadian system's sensitivity to entraining agents. Regular behavioral
      rhythms may be conducive to continued good health and well-being.

PMID- 9167888
TI  - The dosing-time dependent influence of chronic cyclosporin A treatment on daily
      profiles of plasma glucose and insulin in the Wistar rat.
AB  - The dosing-time dependent effects of cyclosporin A (CsA) on glucose and insulin
      plasma levels were evaluated in the light of possible alterations of their
      biological rhythms. Male Wistar rats weighing 200-250 g were habituated to a
      12:12 h light-dark cycle. At the beginning of the experiments, on day D0 (before
      any treatment), significant rhythms were obtained for plasma glucose and
      immunoreactive insulin (IRI). The plasma glucose showed a 12 h periodicity and
      the plasma IRI a more pronounced rhythm, with both 12 h and 24 h significant
      components. Plasma glucose and IRI were then determined in drug-treated (20 mg
      CsA/kg b.wt/day; dosing time point: T01, T07, T13, or T20) and control rats
      during and after a 21-day treatment period. The CsA-treated rats developed
      hyperglycemia and a marked enhancement of the amplitude of the daily glucose
      rhythm. The magnitude of these effects differed among the groups (p < 0.001).
      Most pronounced alterations were observed on day 21 (D21) in group T07: M = 22.5
      +/- 4.0 mmol/l; A = 9.2 +/- 6.0 mmol/l. The mean plasma insulin showed little
      though significant (p < 0.01) decreases. For instance, on D21 in group T01, M =
      28.5 +/- 3.6 microU/ml, and in group T07, M = 28.7 +/- 2.5 microU/ml. In
      parallel, plasma CsA levels increased during the 21-day period and differed among
      groups (p < 0.01). The highest levels (4-5 mg/l) were obtained in T07 and T19 on
      D21. After drug cessation, the levels of plasma glucose were reduced, but stayed
      higher than control values. Body weights were monitored; the rate of growth was
      lower (p < 0.01) in CsA-treated rats than in controls (2.93 +/- 0.11 versus 5.1
      +/- 0.11 g/day, respectively).

PMID- 9167891
TI  - Variability in the period of the blood pressure circadian rhythm in human beings.
AB  - In studies and assessments of human beings done in natural settings, it is
      assumed that the period tau of circadian rhythms, including ones of systolic
      (SBP) and diastolic (DBP) blood pressure, is equal to 24 hours. To test this
      hypothesis, SBP and DBP rhythms were studied in 112 medication-free, non
      hospitalized subjects (62 males, 47.1 + 2.0 years [x +/- SEM], and 50 females,
      54.5 +/- 2.1 years) by 48 h ambulatory blood pressure monitoring (ABPM). Of
      these, 26 were hypertensive (diurnal SBP > 140 mmHg and diurnal DBP > 90 mmHg)
      and 86 normotensive. All subjects were synchronized by their habitual daytime
      activities from approximately 08:00 h to approximately 23:00 h +/- 1 h and by
      sleep at night. The BP was assessed at 15-minute intervals during a continuous
      48h span using a Spacelabs model #90207 ABPM. The time series data of each
      subject were individually evaluated by power spectra analysis for the prominent
      tau of the SBP and DBP rhythms. The prominent tau differed from 24 hours in
      22/112 subjects for SBP and in 16/112 subjects for DBP. Generally, in these
      individuals the tau was less than 24 hours. The occurrence of non-24 h tau's was
      more frequent in hypertensive than normotensive subjects; the difference between
      the groups in the distribution of the prominent tau's by class (tau = 24 h, tau =
      12, 12 h > tau < 24 h, etc.) was statistically significant (chi 2 test = 19.1; p
      < 0.001). No difference in the distribution of tau's of blood pressure was
      detected according to the subject's age and gender. These findings suggest that
      ABPM done only for a duration of 24 h may be too short to characterize accurately
      the features of the day-night variation in human BP, including the precise period
      of its rhythm.

PMID- 9167892
TI  - Bilirubin, REM sleep, and phototransduction of environmental time cues. A
      hypothesis.
AB  - The prevailing hypothesis for phototransduction is that visual (rod or cone)
      pigments mediate light's primary effects on biological clock systems. Common
      light-responsive chronobiological behavioral properties of plants and animals and
      some common molecular structures of plants and animals suggest the possibility
      that heme moieties and bile pigments in animals mediate some nonvisual influences
      of light on neuroactive gases and biological rhythms. As plant phytochrome resets
      the plant biological clock, the similar chromophore in bile pigments is proposed
      to transduce environmental light zeitgeber signals to endogenous biological
      clocks. The temporal association of plasma bilirubin and rapid-eye-movement (REM)
      sleep in populations, the correlation of secretion of biliary bilirubin with REM
      sleep among 10 different species (Spearman r = 0.89, p < 0.002), and the known
      responses of bilirubin to light lead to the hypothesis that bilirubin, in
      particular, plays an evolutionary role in the regulation of REM sleep and in
      mediating some of light's antidepressant effects.

PMID- 9167893
TI  - Small genetic effects in complex diseases: a review of regulatory sequence
      variants in dyslipoproteinemia and atherosclerosis.
AB  - OBJECTIVE: Most reported mutations that affect lipoprotein metabolism are found
      within the coding sequences of genes. Recently, a few mutations that occur within
      promoter sequences have been detected. These promoter sequence variants are the
      topic of the present review. METHODS: Some of these variants are fairly common
      genomic variants in the promoter regions for candidate genes in lipoprotein
      metabolism, such as APOA1, APOC3, LPA, and LPL. It is possible that such
      regulatory sequence variants can result in chronic, modestly altered levels of
      expression of qualitatively normal gene products. This might have a cumulative
      effect on quantitative phenotypes, such as plasma lipoprotein concentrations,
      over the long term. Such an effect might not be detected by existing clinical,
      biochemical, and/or physiological assays. RESULTS: At present, the most
      consistent evidence from several lines of experiments indicates that genomic
      variation in the APOC3 promoter creates slightly elevated plasma triglyceride
      concentrations within the physiologic range. This altered expression appears to
      predispose to hypertriglyceridemia in the presence of secondary factors. Genetic
      variants that produce small effects on promoter function might thus be one
      component of the predisposition to complex diseases. CONCLUSION: The aggregate of
      many small effects may create or contribute to a background of susceptibility
      that, under appropriate conditions, leads to development of frank dyslipidemia
      and atherosclerosis.

PMID- 9167894
TI  - Clinical chemistry and molecular biology of homocysteine metabolism: an update.
AB  - OBJECTIVE: To summarize recent developments in our understanding of homocysteine
      as a clinically relevant and independent predictor of vaso-occlusive disease
      (including atherosclerosis and thromboembolism), as an early indicator of folate
      or cobalamin deficiency, and as a key factor in the pathogenesis of neural tube
      defects. METHODS AND RESULTS: To determine total homocysteine, plasma or serum
      must be separated shortly after collection and subjected to chemical reduction.
      Reference intervals should take into account the prevalence of physiological
      hyperhomocystinemia. A common cause of hyperhomocystinemia is a genetic
      predisposition caused by a polymorphic substitution in the
      methylenetetrahydrofolate reductase (MTHFR) gene, which can be readily detected
      by molecular means. CONCLUSION: Determination of homocysteine and MTHFR testing
      should be limited to laboratories with relevant expertise and ability to maintain
      the high degree of precision required for reliable interpretation. Assays should
      be offered in selected cases with clinical features or laboratory findings
      suggestive of hyperhomocystinemia, since treatment is simple and may be highly
      effective.

PMID- 9167895
TI  - Precision of the magnesium determination in mononuclear blood cells and
      erythrocytes.
AB  - OBJECTIVE: Establishing the analytical variation and reproducibility of the
      intracellular magnesium (Mg) assay in mononuclear blood cells (MBC) and
      erythrocytes (RBC). DESIGN AND METHODS: We assessed the analytical variation of
      the several determination steps, and the reproducibility for the complete
      intracellular Mg-assay (combination of preanalytical, analytical, and biological
      variation). The influence of platelets was determined by comparing Mg
      concentrations obtained from heparinized blood and defibrinated blood. RESULTS:
      Coefficients of variation of the several determination steps used in the MBC- and
      RBC-assay were < or = 5.4%. The overall analytical variation was 5.0-6.8%, and
      reproducibility of the complete Mg-assay 11.6-14.0%. Mg measurements in MBC
      (expressed as fmol/cell) obtained from heparinized blood showed significantly
      higher values than those obtained from defibrinated blood. CONCLUSION: This is
      the first study to describe in detail reproducibility data for the individual
      steps in the overall procedure to measure intracellular magnesium. It is shown
      that results obtained in daily practice should be interpreted with care.
      Moreover, the removal of platelets is essential in the determination of Mg in
      MBC.

PMID- 9167896
TI  - Flow cytometric cell cycle kinetics and quantitative measurement of c-erbB-2 and
      mutant p53 proteins in normal, hyperplastic, and malignant endometrial biopsies.
AB  - OBJECTIVES: The purpose of this study is to biologically characterize endometrial
      hyperplasia by investigating changes in DNA ploidy pattern, the expression of c
      erbB-2 p185 and mutant p53 proteins. METHODS AND RESULTS: Our results show that
      all normal endometria (n = 62) were exclusively diploid and 2 (2.5%) of 79
      endometrial hyperplasias and 22 (68.8%) of 32 endometrial carcinomas were
      aneuploid. Upper 95% normal values for synthetic phase fraction (SPF), c-erbB-2
      and p53 were applied as cut-off values to discriminate between normal and
      malignant endometria. When 9%, 3.2 HNU (Human Neu Unit)/microgram protein, and
      0.39 ng/mg protein were used as cut-off values for SPF. c-erbB-2, and p53
      respectively, 13.9%, 20.2%, and 0% of endometrial hyperplasia and 50%, 56.3%, and
      12.5% of endometrial carcinoma showed raised levels of the corresponding
      parameters. CONCLUSIONS: Our results indicate that subsets of endometrial
      hyperplasia are biologically different as evidenced by the presence of DNA
      aneuploidy, high SPF and c-erbB-2 overexpression, which may provide biological
      markers for assessing progression to endometrial carcinoma.

PMID- 9167897
TI  - Genetic variations of the apo E-CI-CII cluster gene in Koreans.
AB  - OBJECTIVES: To investigate the allele frequencies of the apolipoprotein (apo) E
      CI-CII cluster gene in Koreans, and its relation to plasma lipid and lipoprotein
      levels. METHODS: The study subjects consisted of healthy Korean individuals (apo
      E, 145; apo CI and CII, 81) who were randomly selected via health screening. For
      polymorphism analysis, DNA was amplified by polymerase chain reaction (PCR). The
      one-way analysis of variance (ANOVA) test was performed to compare the mean of
      lipid levels among different genotypes. RESULTS: The apo E polymorphism in the
      Korean population appeared as the E4/2, E3/2, E3/3, E4/3, and E4/4 genotypes. The
      epsilon 3 allele was the most frequent, as in other populations. The apo E
      polymorphism showed the lack of association with plasma lipid levels in this
      population. On the other hand, we demonstrated AvaII polymorphism of the apo CII
      gene by PCR technique. Cholesterol and triglyceride levels were varied
      significantly among the AvaII genotypes (p < 0.05). CONCLUSION: No effect of the
      apo E allele on lipid levels was seen in the Korean population. This result
      suggests that it might be one of the factors in explaining the low prevalence
      rate of atherosclerosis in the Korean population. Also, the AvaII polymorphism
      analysis by PCR is a simple and less time-consuming method.

PMID- 9167899
TI  - Evaluation of serum glycated lipoprotein(a) levels in noninsulin-dependent
      diabetic patients.
AB  - OBJECTIVE: Serum Lp(a) levels are generally considered unaffected by non-insulin
      dependent diabetes mellitus (NIDDM). However, high Lp(a) concentrations as well
      as an increased rate of nonenzymatic glycation of proteins may be involved in
      degenerative diabetic complications. DESIGN AND METHODS: We measured serum
      glycated Lp(a) levels in 17 NIDDM patients, as compared to 14 normoglycaemic
      controls. Glycated proteins were separated from nonglycated ones by boronate
      affinity chromatography, and specific proteins assayed by immunonephelometric
      methods in both fractions. RESULTS: The percentage of glycated Lp(a) was 1.5 +/-
      0.4% (mean +/- SD) in the control group, and was significantly higher in NIDDM
      patients: 4.3 +/- 1.5% (p < 0.01). The basal level of Lp(a) glycation was lower
      than that of other proteins, particularly apo B (4.0 +/- 0.7%). By contrast, the
      variations of glycated Lp(a) levels were of greater amplitude (+ 187%) than those
      of glycated apo B (+ 67%). Glycated Lp(a) values were significantly elevated in
      patients with micro and macrovascular complications in comparison with
      uncomplicated patients. CONCLUSIONS: These results suggest that glycated Lp(a)
      may be considered a potentially interesting parameter in the pathophysiology of
      diabetic vascular complications.

PMID- 9167898
TI  - HDL3 exerts more powerful anti-oxidative, protective effects against copper
      catalyzed LDL oxidation than HDL2.
AB  - OBJECTIVE: To evaluate which HDL subfraction, HDL2 or HDL3 exerts the greater
      preventive effect on the Cu(2+)-induced LDL oxidation. METHODS: LDL was incubated
      for 6 h with 2.5 microM Cu2+ in phosphate-buffered saline alone, or in the
      presence of HDL2 or HDL3 at various protein concentrations. Each sample was
      subjected to agarose gel electrophoresis, and the amount of lipid hydroperoxide
      in each sample of LDL was measured. RESULTS: There was no significant difference
      in the levels of LPO between the LDL and LDL + HDL2 cases, whereas a significant
      reduction was apparent with LDL + HDL3. Both HDL2 and HDL3 significantly
      inhibited oxidative modification of LDL, as assessed by electrophoretic mobility,
      in a concentration dependent manner, but this effect was much more pronounced
      with HDL3. CONCLUSION: HDL3 may play an important role in the prevention of
      atherosclerosis in vivo, more effectively inhibiting oxidation of LDL than HDL2.

PMID- 9167900
TI  - Time-resolved fluoroimmunoassay of terfenadine in human serum.

PMID- 9167901
TI  - Metallothionein, zinc and copper levels: relationship with acute myocardial
      infarction.

PMID- 9167902
TI  - To whom do we propose a definitive method?

PMID- 9167903
TI  - Human papillomaviruses: general features.

PMID- 9167904
TI  - Papillomavirus and HPV typing.

PMID- 9167905
TI  - Oncogenes and antioncogenes in the development of HPV associated tumors.

PMID- 9167906
TI  - In vitro experimental systems for HPV: epithelial raft cultures for
      investigations of viral reproduction and pathogenesis and for genetic analyses of
      viral proteins and regulatory sequences.

PMID- 9167907
TI  - Tissue xenografts as a model system for study of the pathogenesis of
      papillomaviruses.

PMID- 9167908
TI  - The rabbit viral skin papillomas and carcinomas: a model for the immunogenetics
      of HPV-associated carcinogenesis.

PMID- 9167909
TI  - Humoral immune response to human papillomavirus infection.

PMID- 9167910
TI  - Cellular immunity in cutaneous and genital HPV infections.

PMID- 9167911
TI  - Vaccination against papillomavirus in cattle.

PMID- 9167912
TI  - Strategies for immunoprophylaxis and immunotherapy of papillomaviruses.

PMID- 9167913
TI  - HPV infection: future prospects.

PMID- 9167914
TI  - The insulin resistance syndrome.

PMID- 9167915
TI  - Hypersensitivity pneumonitis.

PMID- 9167917
TI  - Pulmonary metabolism of biogenic amines.

PMID- 9167916
TI  - Approach to the patient with unexplained chest pain.

PMID- 9167918
TI  - Management of the older person after MI.

PMID- 9167919
TI  - Treatment of chronic hepatitis C.

PMID- 9167920
TI  - Management of the colicky infant.

PMID- 9167921
TI  - Cardiac disease & stroke: innocent bystander or cause & effect?

PMID- 9167922
TI  - Focus.

PMID- 9167923
TI  - The chevron osteotomy: a clinical and radiographic analysis.
AB  - This is a retrospective study of the chevron osteotomy for hallux valgus.
      Subjective and objective postoperative results were evaluated. Differences in the
      postoperative correction of the intermetatarsal 1-2 angle and the first
      metatarsophalangeal angle were noted using two accepted measurement methods.
      Seventeen patients (23 feet) with an average age of 39 years (range, 15-51 years)
      and an average follow-up of 3 years (range, 1-5 years) were studied. The average
      preoperative intermetatarsal 1-2 angle was 11 degrees (range, 8 degrees to 14
      degrees), and the average hallux valgus angle was 23 degrees (range, 7 degrees to
      39 degrees). The apparent postoperative correction differed depending on the
      method of measurement used. One method consistently indicated a greater amount of
      correction in both the intermetatarsal and metatarsophalangeal angles. The
      chevron procedure resulted in an overall satisfactory improvement of symptoms,
      function, and cosmesis. Four feet exhibited postoperative radiographic changes
      that could be construed as avascular changes, but there was no collapse noted,
      nor were there clinical symptoms of avascular necrosis. No nonunions, malunions,
      or infections developed, and no cases of hallux varus occurred.

PMID- 9167924
TI  - Syndesmotic screw placement: a biomechanical analysis.
AB  - At the present time, syndesmotic screw fixation is recommended when there is a
      tibiofibular diastasis, a Maisonneuve fracture, or syndesmotic instability after
      fixation of distal tibia-fibula fractures. The aim/purpose of this study was to
      demonstrate the optimal level of syndesmotic screw placement before creation of a
      Maisonneuve fracture. Legs of 17 embalmed cadavers underwent knee
      disarticulation. The legs were then dissected to expose the
      syndesmosis/interosseous membrane. The paired cadaver legs were tested in two
      groups. In group I (10 pairs), the left legs were tested without any syndesmotic
      fixation and the right legs were tested with the syndesmosis fixed at 2.0 cm
      above the tibiotalar joint. In group II (7 pairs), the syndesmosis in each left
      leg was fixed at 3.5 cm above the tibiotalar joint and the right leg syndesmosis
      was fixed at 2.0 cm above the tibiotalar joint. After ligament section and
      syndesmosis fixation, each leg was then jig mounted with transfixing wires
      through the proximal tibia and calcaneus. The ankle was placed in neutral with 15
      degrees of pronation and a load of 150 pounds and a strain gauge anchored
      medially and laterally. The proximal tibia was internally rotated while the ankle
      was held fixed until syndesmotic, bony, or hardware failure occurred. Torsional
      force, the degree of rotation and the amount of syndesmotic widening were
      quantitated. Two-tailed t-test comparing no fixation with fixation at 2.0 cm
      indicated less syndesmotic widening with screw placed at 2.0 cm (P = 0.04). Two
      tailed t-test comparing screw fixation at 2.0 cm and 3.5 cm indicated less
      syndesmotic widening with screw placed at 2.0 cm (P = 0.07). It would seem
      reasonable to place a syndesmotic screw at 2.0 cm above tibiotalar joint.

PMID- 9167925
TI  - Treatment of fractures of the fifth metatarsal: a prospective study.
AB  - Successful treatment of avulsion fractures of the base of the fifth metatarsal
      has been achieved using both short leg casts and soft (Jones) dressings. Sixty
      patients who presented to our institution were prospectively randomized to be
      treated with either a short leg cast or a soft (Jones) dressing for the purpose
      of assessing the efficacy of each treatment modality. Our results demonstrated
      that radiographic evidence of fracture healing was present in all patients by 65
      days with 44 days representing the average elapsed time for such change. All
      patients returned to full weightbearing and full physical activity within 96
      days. Significantly, the average length of recuperation for patients treated with
      a soft (jones) dressing was 33 days as compared to 46 days for those treated with
      a short leg cast. Also, the average modified foot score for patients treated in a
      soft dressing was 92 (excellent) compared to 86 (good) for patients treated in a
      short leg cast. We conclude that a soft dressing allows patients to return to pre
      injury levels of activity faster than when treated in a short leg cast and
      without compromising clinical or radiographic union of avulsion fractures of the
      base of the fifth metatarsal.

PMID- 9167926
TI  - Pedodynographic measurements after forefoot reconstruction in rheumatoid
      arthritis patients.
AB  - From January 1987 to December 1992, 38 patients (59 feet) with rheumatoid
      arthritis underwent reconstruction of the forefoot using Keller-Lelievre
      arthroplasty of the first metatarsophalangeal joint and Hoffman resection of the
      lesser metatarsal heads. The average age of the patients was 61.3 years, with
      both feet involved in 21 patients and 17 with single foot involvement. The aim of
      our study was to evaluate the results both on a functional and an objective basis
      using dynamic and static pedodynographic measurements. Attention was given to
      dynamic pressure measurements under the metatarsal heads, the center of pressure
      distribution, gait analysis, and peak loads taken on different areas of the
      forefoot during normal walking. Correlations were made between these measurements
      and symptoms. After a mean follow-up time of 35 months, the clinical results were
      satisfactory in 54%, satisfactory with some reservations in 39%, satisfactory
      with major reservations in 3%, and unsatisfactory in 3% of patients.

PMID- 9167927
TI  - Physiological elongation of ligamentous complex surrounding the hindfoot joints:
      in vitro biomechanical study.
AB  - Ligaments surrounding the hindfoot joints play an important role in hindfoot
      stability. This in vitro study investigated anatomical and biomechanical
      characteristics of nine major ligamentous structures, including length and
      orientation at neutral position and physiological elongation with the foot in
      five different positions relative to the neutral position. The results showed
      that ligament elongation depended on the ligament length, orientation in neutral
      position, and movement of bones to which they were attached.

PMID- 9167928
TI  - Treatment of Morton's neuroma by neurolysis.
AB  - Thirty-five patients who had undergone neurolysis for Morton's neuroma were
      reviewed at a mean of 21.4 months. Those patients who had received diagnostic
      lidocaine (local anesthetic) injections as an evaluation tool before the
      operation did extremely well after this operation. Overall patient satisfaction
      was found to be extremely high, with 17 of 35 patients enjoying complete relief
      of their pain and 12 of 35 reporting minimal discomfort with activity. The
      likelihood of persistent symptoms seemed to be related to the presence of
      associated foot disorders.

PMID- 9167929
TI  - Vascular supply of nerves in the tarsal tunnel.
AB  - The normal vascular supply of nerves in the tarsal tunnel was studied by intra
      arterial injection of latex. In general, the blood supply to the tibial nerve and
      its branches came directly from corresponding arteries. Each nutrient artery to
      the tibial nerve bifurcated on the surface of the lateral plantar nerve
      fasciculus to create longitudinal vessels that made anastomoses with bifurcating
      nutrient vessels proximally and distally. This primary longitudinal system
      supplied intersubfascicular vessels to the medial plantar fasciculus. The last
      nutrient artery from the posterior tibial artery usually supplied the terminal
      branching point of the tibial nerve midway through the tarsal tunnel. The lateral
      and medial plantar nerves received most of the nutrient vessels from their
      corresponding arteries in shorter intervals. In 65% of cases, the lateral plantar
      nerve received a nutrient vessel from the medial plantar artery. Potential
      anatomical areas of vascular compromise in the etiology or surgical release of
      tarsal tunnel syndrome are discussed.

PMID- 9167930
TI  - Autogenous bone grafting of hallux sesamoid nonunions.
AB  - We first performed autogenous bone grafting for lesions of the hallux sesamoid in
      1984. During the next 9 years, 21 patients (11 men and 10 women with an average
      age of 34 and 32 years, respectively) underwent this surgical procedure for
      symptomatic tibial hallux sesamoid non-unions. Successful bony union was achieved
      in all but two patients. The majority of patients obtained concomitant relief of
      preoperative symptomatology and returned to their preinjury level of activity. We
      believe that this procedure serves as an alternative to hallux sesamoid excision
      in selected cases.

PMID- 9167931
TI  - Pathology of the Achilles tendon in association with ciprofloxacin treatment.
AB  - Achilles tendon pain or rupture after fluoroquionolone treatment has been
      described as an uncommon adverse effect. We report two patients with
      ciprofloxacin-associated Achilles tendon disease, one with histopathological
      examination. Microscopic evaluation showed irregular collagen fiber arrangement,
      hypercellularity, and increased interfibrillar glycosaminoglycans. These
      pathological features are also seen in tendon overuse injuries in athletes.

PMID- 9167932
TI  - Revision ankle fusion using internal compression arthrodesis with screw fixation.
AB  - We reviewed 20 revision ankle fusions performed using internal compression
      arthrodesis with screw fixation. Clinical, functional, and radiographic results
      were measured at an average follow-up of 30 months (range, 12-50 months). The
      reasons for the index procedures were nonunion in 11, malunion in 7, infected
      nonunion in 1, and nonunion associated with avascular necrosis of the talus in 1
      case. Fusion occurred in 15 of 20 patients. Two additional patients obtained
      fusion after subsequent procedures, for a final union rate of 85%. The average
      time to fusion was 6 months (range, 2-32 months). Nineteen additional operations
      were necessary in 12 patients, including three amputations for chronic infection
      (two infected nonunions and one chronic osteomyelitis). All but one patient had a
      plantigrade limb at follow-up. Seventeen of 20 patients were satisfied with their
      ultimate outcome, including all three patients with amputations. The three
      dissatisfied patients were bothered by chronic pain. Revision ankle fusion for
      nonunion or malunion using internal compression arthrodesis with screw fixation
      is beneficial for most patients. It is a technically demanding procedure that is
      associated with a high complication rate. Many patients can be expected to have
      residual pain. We emphasize the need for accurate alignment and early, aggressive
      treatment of infectious complications. Amputation should be considered a viable
      option to improve functional outcome in patients with solid, well-aligned fusions
      who are disabled by severe chronic pain.

PMID- 9167933
TI  - Technique tip: the Orthoplast slipper cast.

PMID- 9167934
TI  - Recurring desmoid tumor of the foot: a case study.

PMID- 9167935
TI  - Separation of representative lipid compounds of biological membranes and lipid
      derivatives from peroxidized polyunsaturated fatty acids by reversed phase high
      performance liquid chromatography.
AB  - A complex mixture of different lipid compounds, including phosphatidylcholine,
      phosphatidylserine, all trans-retinol, 15(S)-hydroperoxyeicosatetraenoic acid, D
      alpha-tocopherol, saturated and unsaturated fatty acids can be separated by
      reversed phase HPLC by using a C-18, 120 mm x 4 mm, 3 microns particle size
      column and a step gradient from acetonitrile/water (1:1; v:v) to 100%
      acetonitrile at a flow rate of 0.8 ml/min. By applying this elution condition,
      separation of various groups of lipid hydroperoxides and lipid derivatives, each
      one originating from a different in vitro peroxidized polyunsaturated fatty acid,
      can be obtained. Simultaneous detection is carried out by a diode array detector
      at a wavelength accumulation range set up between 195 and 400 nm. The possibility
      of simultaneously having such a large number of measurements renders this
      chromatographic method particularly suitable in studies concerning lipid
      peroxidation where, in addition to the detection of free radical-induced lipid
      hydroperoxides, data on some key antioxidant molecules, i.e. vitamin A and E, as
      well as that of structural compounds of biological membranes, i.e.
      phosphatidylcholine and phosphatidylserine, can be achieved.

PMID- 9167936
TI  - Free radical production by azomethine H: effects on pancreatic and hepatic
      tissues.
AB  - The antimalarial properties of azomethine H represent the basis for its use as a
      chemotherapeutic agent. This work was carried out in order to verify the
      biological side effects of azomethine H and to clarify the contribution of
      reactive oxygen species (ROS) in this process. It was shown that azomethine H
      increased serum activities of amylase, alanine transaminase (ALT) and the TBARS
      concentrations, in rats. No changes were observed in glutathione peroxidase and
      catalase activities. The drug-induced tissue damage might be due to superoxide
      radicals (O2.-), since Cu-Zn superoxide dismutase activities were increased by
      azomethine H treatment. This study allows tentative conclusions to be drawn
      regarding which reactive oxygen metabolites play a role in azomethine H activity.
      We concluded that (O2.-) maybe produced as a mediator of azomethine H action.

PMID- 9167937
TI  - Effects of respiratory burst inhibitors on nitric oxide production by human
      neutrophils.
AB  - Human neutrophils (PMN) activated by N-formylmethionyl-leucyl-phenylalanine
      (fMLP) simultaneously release nitric oxide (.NO), superoxide anion (O2.-) and its
      dismutation product, hydrogen peroxide (H2O2). To assess whether .NO production
      shares common steps with the activation of the NADPH oxidase, PMN were treated
      with inhibitors and antagonists of intracellular signaling pathways and
      subsequently stimulated either with fMLP or with a phorbol ester (PMA). The G
      protein inhibitor, pertussis toxin (1-10 micrograms/ml) decreased H2O2 yield
      without significantly changing .NO production in fMLP-stimulated neutrophils; no
      effects were observed in PMA-activated cells. The inhibition of tyrosine kinases
      by genistein (1-25 micrograms/ml) completely abolished H2O2 release by fMLP
      activated neutrophils; conversely, .NO production increased about 1.5- and 3-fold
      with fMLP and PMA, respectively. Accordingly, orthovanadate, an inhibitor of
      phosphotyrosine phosphatase, markedly decreased .NO production and increased O2.-
      release. On the other hand, inhibition of protein kinase C with staurosporine and
      the use of burst antagonists like adenosine, cholera toxin or dibutyryl-cAMP
      diminished both H2O2 and .NO production. The results suggest that the activation
      of the tyrosine kinase pathway in stimulated human neutrophils controls
      positively O2.- and H2O2 generation and simultaneously maintains .NO production
      in low levels. In contrast, activation of protein kinase C is a positive
      modulator for O2.- and .NO production.

PMID- 9167938
TI  - Unidentified antioxidant defences of human plasma in immobilized patients: a
      possible relation to basic metabolic rate.
AB  - Plasma total peroxyl radical scavenging capacity was studied in terminal patients
      who were chronically immobilized because of an acute (stroke) or chronic
      neurodegenerative disease (Alzheimer's disease). A luminometric assay was used to
      measure total antioxidant capacity (TRAP). The immobilized patients showed
      significant decrease in TRAP primarily because of a decrease in the concentration
      of unknown antioxidants. Our results suggest that human plasma may contain
      unknown antioxidants, the regulation of which could be related to the basic
      metabolic rate.

PMID- 9167939
TI  - Multiplicity of antioxidant enzyme catalase in mouse liver cells.
AB  - Multiplicity of catalase activity has been observed in crude homogenates from the
      tissue and cell lines of mouse liver by ethanol/Triton X-100/heat treatment. The
      five enzymatically active catalase bands were designated as CAT1, CAT2, CAT3,
      CAT4, and CAT5 with a nondenatured molecular mass of 270kDa, 258kDa, 229kDa,
      210kDa, or 197kDa, respectively. Cultured mouse liver cell lines, mouse liver
      tissue homogenate, and pure mouse liver catalase showed only one catalase band
      (CAT1) after ethanol/Triton X-100 treatment at 4 degrees C for 72 hr. The same
      treatment but incubated at 37 degrees C for 72 hr yielded three bands (CAT2,
      CAT4, CAT5) in normal cell line, only one band (CAT5) in MNNG-transformed and
      SV40-transformed cells, two bands (CAT1, CAT4) in mouse liver tissue homogenates,
      and two bands (CAT1, CAT3) in pure mouse liver catalase. These five catalase
      bands were further biochemically characterized. The CAT1, CAT2, and CAT3 are
      sensitive to heat (68 degrees C, 1 min), while CAT4 and CAT5 are rather heat
      resistant. The sensitivity to catalase inhibitors, such as aminotriazole, azide,
      or cyanide varies among the isoforms. Protease inhibitors could prevent the
      formation of CAT3 and CAT4, but not CAT5. Treatment with protease, however,
      removed all forms of catalase except CAT5. We conclude from this study that the
      appearance of different catalase bands is likely due to epigenetic modification
      of the protein, particularly proteolysis. The lowered catalase activity in
      transformed cells might also be attributable to the loss of two catalase
      isoforms.

PMID- 9167940
TI  - Toxicity of polyunsaturated fatty acid esters for human monocyte-macrophages: the
      anomalous behaviour of cholesteryl linolenate.
AB  - We have investigated the toxicity to human monocytemacrophages, and
      susceptibility to oxidation, of different individual dietary fatty acids in
      cholesterol esters and triglycerides, added to the cell cultures as coacervates
      with bovine serum albumin. Toxicity was assessed using release of radioactivity
      from cells preloaded with tritiated adenine. Lipid oxidation was measured by gas
      chromatography (GC). The triglycerides showed a direct relationship between
      toxicity and increasing unsaturation, which in turn correlated with increasing
      susceptibility to oxidation. Triolein (18:1; omega-9) and trilinolein (18:2;
      omega-6) were non-toxic. Trilinolenin (18:3; omega-3) was toxic only after
      prolonged incubation. Triarachidonin (20:4; omega-6), trieicosapentaenoin (20:5;
      omega-3) and tridocosahexaenoin (22:6; omega-3) were profoundly and rapidly
      toxic. There was a similar relationship between toxicity and increasing
      unsaturation for most of the cholesterol esters, but cholesteryl linolenate was
      apparently anomalous, being non-toxic in spite of possessing three double bonds
      and being extensively oxidised. Probucol and DL-alpha-tocopherol conferred
      protection against the toxicity of cholesteryl arachidonate and triarachidonin.
      The oxidation in these experiments was largely independent of the presence of
      cells. GC indicated that formation of 7-oxysterols might contribute to the
      toxicity of cholesteryl linoleate. The toxicity of triglycerides suggests that
      polyunsaturated fatty acid peroxidation products are also toxic. Possible
      mechanisms of cytotoxicity and relevance to atherosclerosis are discussed.

PMID- 9167941
TI  - A novel animal model to evaluate oxygen derived free radical damage in soft
      tissue.
AB  - We present a novel animal model which allows the continuous intra-arterial
      infusion in one hindlimb of non-anaesthetized rats, without inducing ischemia.
      Using this model the effect of continuous infusion (1 ml/h) for 24 h with tert
      butylhydroperoxide (tert-BuOOH) at a concentration of 25 mM on soft tissue of the
      left hind limb was studied and compared to the effect of saline infusion (control
      group). The tert-BuOOH-infused foot showed increased skin temperature, increased
      circumference, redness of the plantar skin, impaired function and increased pain
      sensation, while in the contralateral foot and in rats only perfused with saline
      these signs of inflammation were absent (p < 0.01). Histological analysis of the
      left gastrocnemius muscle showed edema, muscle cell degeneration with a patchy
      distribution pattern and vascular damage. All these features increased in
      severity from 4 to 24 h tert-BuOOH infusion. After 24 h of tert-BuOOH infusion
      infiltration of neutrophils in the interstitium was observed. Vascular
      permeability, expressed as left to right gastrocnemius muscle 99mTc-IgG uptake
      ratio, was similarly increased after 4 h (2.09 +/- 0.26) and 12 h (2.04 +/- 0.08)
      of tert-BuOOH infusion compared to saline (1.05 +/- 0.08) (p < 0.001), and
      further increased after 24 h (3.84 +/- 0.13): (p < 0.001). In this animal model
      free radical-related soft tissue damage was induced, by continuous infusion of
      tert-BuOOH, followed by increasing necrosis and vascular permeability in skeletal
      muscle coinciding with neutrophilic infiltration.

PMID- 9167942
TI  - Liposomes containing alpha-tocopherol and ascorbate are protected from an
      external oxidant stress.
AB  - The interaction between alpha-tocopherol and ascorbate in protecting membrane
      lipids from peroxidation was studied in unilamellar liposomes in which alpha
      tocopherol was incorporated into the liposomal membrane, and ascorbate was
      trapped within the vesicles. Extravesicular ferricyanide was reduced by ascorbate
      derived electrons, and this was enhanced by the presence of alpha-tocopherol in
      the lipid bilayer. When a water-soluble free radical initiator was added to the
      outside of liposomes, intravesicular ascorbate prevented oxidation of alpha
      tocopherol, and this effect was associated with complete protection against
      peroxidation of membrane lipids. These results suggest that ascorbate-dependent
      recycling of alpha-tocopherol can protect biological membranes from peroxidation
      by oxidants originating across the membrane bilayer from ascorbate.

PMID- 9167943
TI  - Why do we expect carotenoids to be antioxidants in vivo?

PMID- 9167944
TI  - Targeted oncogenesis in the thyroid of transgenic mice.
AB  - We have developed mouse models for tumors affecting the epithelial cellular
      compartment of the thyroid which has been targeted using the bovine thyroglobulin
      (bTg) promoter. Transgenic mice expressing the human activated c-Ha-Ras gene
      developed papillary thyroid carcinomas demonstrating the oncogenic potential of
      activated Ras gene in the thyroid gland. Transgenic mice express the mutant form
      of the alpha subunit of the adenylate cyclase-coupled G alpha s with mutations at
      codon 201 (R201H). The expression of this mutant transgene is not by itself
      sufficient to produce benign tumors or even hyperplasia, but the transgenic mice
      have inherited a predisposition to develop thyroid adenomas.

PMID- 9167945
TI  - Protein kinase C alpha and tumorigenesis of the endocrine gland.
AB  - A point mutation in the protein kinase C alpha (PKC alpha) gene has been
      discovered in a subpopulation of human pituitary tumors characterized by their
      invasive phenotype. Here we show that: (1) thyroid tumors can express the PKC
      alpha mutation detected in a subpopulation of follicular adenomas and carcinomas,
      and (2) mutated PKC alpha has modified enzymatic properties as compared to wild
      type PKC alpha. It has lost its capacity to phosphorylate the S17R substrate and
      exhibits a higher sensitivity to degradation as compared to wild-type PKC alpha.
      In conclusion, the presence of the PKC alpha mutant in tumors other than
      pituitary tumors and the observation that the presence of the point mutation
      induces changes in PKC alpha properties suggest the involvement of this mutant in
      tumorigenesis.

PMID- 9167946
TI  - Origin and progression of thyroid epithelial tumours: cellular and molecular
      mechanisms.
AB  - Tumours of the thyroid follicular cell are proving to be one of the most
      informative models for "dissecting' the molecular genetics of multi-stage human
      tumorigenesis. Early thyroid tumour development is closely correlated with
      mutation of five alternative genes, ras, ret, trk, gsp and the TSH receptor,
      associated with different tumour phenotypes, providing an excellent example of
      genotype/phenotype correlation. For two of these genes, ras and ret, there is
      also direct experimental evidence from gene transfer studies that they are
      sufficient to initiate tumorigenesis, one of very few situations where such proof
      of causality has been obtained for a human tumour. Much less is known of the
      molecular basis of malignant transformation in thyroid. However, the rare,
      further progression to undifferentiated (anaplastic) cancer provides a
      particularly clear-cut illustration of the role of the tumour-suppressor gene p53
      in human cancer. Furthermore, in vitro data suggest the intriguing possibility
      that the anaplastic phenotype results from a combination of p53 mutation together
      with a spontaneous switch in differentiation programme, i.e. co-operation between
      a genetic and an epigenetic event.

PMID- 9167947
TI  - Clinical consequences of activating germline mutations of TSH receptor, the
      concept of toxic hyperplasia.
AB  - Activating mutations of TSH-R have been described in toxic nodules and more
      recently in familial nonautoimmune thyrotoxicosis. This last entity is still
      confused with familial Graves' disease and the aim of this study is to define its
      phenotype. Based on 49 patients coming from our first family and on the 4 other
      kindreds secondarily described in the literature, the phenotypic expression is: a
      high incidence of hyperthyroidism, an early onset of disease, a higher men/women
      ratio (17/32) than in Graves, disease, the absence of ophthalmopathy and of
      circulating and intrathyroid signs of immunity, a pathology similar to toxic
      nodule, the need for a total destruction of thyroid tissue to cure the patients.
      The total analogy with toxic nodule leads us to name this new entity "toxic
      hyperplasia'. Among 92 successive diffuse nonfamilial thyrotoxicosis cases
      (initially considered as Graves) we isolated 5 cases without extra- and
      intrathyroidal autoimmunity, raising the question of the existence of an apparent
      "sporadic' form of toxic hyperplasia (neomutation?).

PMID- 9167948
TI  - Targeting medullary thyroid carcinomas with bispecific antibodies and bivalent
      haptens. Results and clinical perspectives.
AB  - The present article reviews the clinical trials that have been performed in
      recurrent medullary thyroid carcinoma patients with the Affinity Enhancement
      System. This technique uses bispecific antibodies to target radiolabelled
      bivalent haptens to tumour cells. Its sensitivity in the detection of known
      tumour sites is high (90%) and this technique also achieves good sensitivity
      (61%) in the detection of occult disease as revealed by abnormal thyrocalcitonin
      blood levels. Due to its high targeting capacity, this technique is now
      considered for use as a therapeutic agent in medullary thyroid carcinoma
      patients.

PMID- 9167949
TI  - RET proto-oncogene mutations in multiple endocrine neoplasia type 2 and medullary
      thyroid carcinoma.
AB  - Multiple endocrine neoplasia type 2 (MEN-2) is a familial cancer syndrome
      inherited in an autosomal dominant fashion with age-related penetrance. The main
      tumour type present in all manifestations of this syndrome. MEN-2A, MEN-2B and
      familial medullary thyroid carcinoma (FMTC), is medullary thyroid carcinoma
      (MTC). MTC arises from the parafollicular or C cells of the thyroid. MEN-2A is
      characterised by the triad of MTC, phaeochromocytoma, and parathyroid
      hyperplasia. MEN-2B is characterised by features similar to those of MEN-2A,
      except for the absence of clinically apparent parathyroid hyperplasia, and
      additional stigmata including a marfanoid habitus, mucosal neuromas and
      ganglioneuromatosis of the gastrointestinal tract. FMTC families have MTC as
      their only phenotype. Missense mutations affecting conserved cysteine codons
      adjacent to the transmembrane domain of the RET proto-oncogene have been
      identified in the germline DNA of patients with MEN-2A and FMTC. A single
      mutation at codon 918 in the tyrosine kinase domain of the RET receptor has been
      associated with the MEN-2B phenotype. In a small number of FMTC families,
      missense point mutations have also been identified in the intracellular domain of
      the RET protein. RET mutation analysis of MEN-2 families has allowed the
      identification of genotype-phenotype correlations. While 25% of all MTCs are
      hereditary, the great majority of MTCs, 75%, are sporadic. Various somatic RET
      mutations have been identified in sporadic MTCs. In a small number of hereditary
      MTCs with germline mutations in RET, an additional somatic missense RET mutation
      has been identified. The discovery of RET mutations in MEN-2 has made possible
      accurate DNA-based diagnosis and predictive testing. The clinical significance of
      somatic RET mutations has yet to be determined.

PMID- 9167950
TI  - Multiple endocrine neoplasia type 1 and the search for the genetic trigger.
AB  - Multiple endocrine neoplasia type 1 (MEN-1) is characterized by primary
      hyperparathyroidism, endocrine pancreatic-duodenal and anterior pituitary tumors.
      The diagnosis is challenging and involves the exclusion of other endocrine
      neoplasia syndromes with overlapping features. The predisposing genetic defect
      was assigned to chromosomal region 11q13 based on linkage analysis. Combined
      tumor and pedigree genotype analysis showed that allele losses in pancreatic,
      parathyroid and pituitary tumors eliminated the wild-type allele at the 11q13
      loci, suggesting inactivation of a tumor suppressor gene in this region. A 5-Mb
      integrated map of the region has been established by the European consortium on
      MEN-1. Based on this mapping the critical interval was restricted to 2 Mb, a
      region within which eight candidate genes are located.

PMID- 9167951
TI  - Tumour suppressor genes in the pathogenesis of human pituitary tumours.
AB  - Abnormal cell proliferation is controlled by opposing actions of oncogene
      products (stimulatory) and tumour suppressor gene (TSG) products (inhibitory).
      The former are dominantly acting, i.e. only one copy needed for tumorigenesis,
      whilst for TSG both copies of the gene must be inactivated so these are recessive
      at a cellular level. For anterior pituitary tumours only one oncogene (Gsp) has
      been identified in a variable proportion (4-40%) of a single tumour subtype
      (somatotrophinomas). Contrariwise, allelic deletion studies, using a PCR-based
      microsatellite polymorphism analysis of DNA extracted from archival specimens,
      have shown significant loss of heterozygosity in 20-40% of all tumour subtypes at
      the locus of the putative MEN-1 gene (chr. 11q13); the retinoblastoma gene (chr.
      13q 12-14), and 10q26. Moreover, these DNA microdeletions were concentrated in
      radiologically invasive tumours compared to noninvasive tumours (modified Hardy
      gdes 3 and 4 vs. 1 + 2). In addition, 50% of Cushing's adenomas showed presence
      of p53 immunopositivity, though no point mutations in exons 4-9 were found, by
      SSCP analysis, to account for this. These studies show that analysis of TSGs in
      pituitary adenomas may provide clues to their pathogenesis, and more importantly
      relate to clinical behaviour of the tumour, and hence aid decisions regarding
      management.

PMID- 9167952
TI  - Molecular mechanisms of parathyroid hyperplasia and neoplasia.
AB  - In the past decade we have witnessed an explosion in our knowledge of the
      molecular bases of hyperparathyroidism. In spite of the generally benign
      phenotype of parathyroid tumors, several of the well-recognized mechanisms in
      tumor biology are applicable to parathyroid tumorigenesis. The concept of
      evolution of nonneoplastic endocrine hyperplasia into a true tumor is as
      operative for the parathyroid tissue as for any other neoplasia. The molecular
      mechanisms underlying parathyroid tumor development, either on the ground of
      tissue hyperplasia or as neoplasia "ab initio', are starting to be recognized.
      Oncogenes as well as tumor-suppressor genes and trophic factors appear to play a
      role in the process of parathyroid tissue growth. The unique opportunity of
      evaluating at least four distinct organs greatly contributed to the knowledge of
      the genetic basis of parathyroid tumor development, a field relatively
      undeveloped in comparison to that of other cancers.

PMID- 9167953
TI  - Genetic testing in presymptomatic diagnosis of multiple endocrine neoplasia.
AB  - Multiple endocrine neoplasias (MEN) are familial diseases characterized by
      endocrine neoplasms and transmitted in an autosomal dominant manner. In MEN type
      1, the major lesions affect parathyroid glands, pancreatic islet cells and
      anterior pituitary. The MEN-1 gene has been mapped to chromosome 11q13 and a set
      of DNA-polymorphic markers localized close to this region provides a useful tool
      for presymptomatic diagnosis in MEN-1 families. MEN type 2 refers to the
      inherited forms of medullary thyroid carcinoma (MTC) associated or not with
      pheochromocytoma and hyperparathyroidism. In MEN-2, germinal mutations of the C
      RET proto-oncogene which is localized on chromosome 10q11 have been found in the
      three clinical and allelic forms of the syndrome respectively, MEN-2 type A, B
      and familial isolated MTC. Mutations of C-RET are found in more than 90% of MEN-2
      patients and genetic screening leads to accurate risk evaluation in families and
      consequently a preventive treatment of MTC and adrenal neoplasms. Recent
      discoveries on MEN syndromes and related familial endocrine disorders have a
      major clinical impact and allow a better understanding of the physiological
      pathways involved in familial as well as in sporadic endocrine tumor
      pathogenesis.

PMID- 9167954
TI  - Management of patients and subjects at risk for multiple endocrine neoplasia type
      1: MEN 1. GENEM 1. Groupe d'Etude des Neoplasies Endocriniennes Multiples de type
      1.
AB  - Multiple endocrine neoplasia type 1 (MEN 1) is characterized by the combined
      occurrence, to variable degree, of hyperparathyroidism (HPT) (85.7% of cases
      according to the French Registry of GENEM 1), tumors of the endocrine pancreas
      (49.6%), pituitary adenomas (38.4%) and, less frequently, adrenal tumors (9.6%)
      and neuroendocrine tumors (5.8%). Currently, diagnosis of MEN 1 is done in the
      fourth decade of life, but familial screening (using genetic tools whose
      diagnostic accuracy approaches 100%) has lowered the age of diagnosis. Screening
      for MEN 1 in a patient harboring an apparently sporadic tumor will depend on the
      endocrine gland involved. Extensive screening for MEN 1 in the presence of HPT
      will be conducted only when the familial history is suggestive, when parathyroid
      glands are hyperplastic or when multiple parathyroid adenomas have been found at
      surgery. All patients with an endocrine pancreas tumor need to be investigated
      for the presence of other endocrine lesions of MEN 1. Extensive screening for MEN
      1 is only recommended when a patient with a pituitary tumor or an adrenal tumor
      has a familial history suggestive of MEN 1. Otherwise regular measurement of
      blood calcium and PTH levels seem sufficient. Extensive screening for endocrine
      lesions when MEN 1 is suspected involves hormone measurements and imaging
      procedures. For the diagnosis of HPT, calcemia and PTH 1-84 must be measured. In
      the absence of clinical symptoms, basal measurement of serum gastrin, glucose,
      insulin, glucagon, VIP, somatostatin and pancreatic polypeptide levels are
      combined with abdominal ultrasonography. When symptoms suggest the Zollinger
      Ellison syndrome, the secretin stimulation test is recommended. The diagnosis of
      a pituitary tumor is made by pituitary imaging and selected hormone assays
      (mainly PRL). To detect an adrenal tumor, CT scan is recommended, combined with
      serum potassium, urinary free cortisol and androgen measurement. When the
      diagnosis of MEN 1 is made, clinical and hormonal follow-up (once a year) and
      imaging surveillance (every 3-5 years) may be sufficient to detect new other
      endocrinopathies (unless suggestive clinical symptoms arise). Surgical management
      of each endocrine lesion must be done by skilled surgeons according to
      therapeutic protocols which have been discussed in detail. Genetic screening is
      an integral part of familial screening which may be conducted in collateral and
      in the offspring of MEN 1 patients. Obviously ethical principles (informed
      consent, etc.) must be respected. As it is now possible to detect presymptomatic
      gene carriers with a high degree of accuracy, follow-up is needed to make
      appropriate management decisions. The marked anxiety provoked by screening in an
      overtly asymptomatic healthy subject must not be underestimated. Conversely, a
      negative genetic diagnosis helps to reassure the subject and avoid repetitive and
      costly follow-up.

PMID- 9167955
TI  - Multiple endocrine neoplasia type 2: management of patients and subjects at risk.
      French Study Group on Calcitonin-Secreting Tumors (GETC).
AB  - Multiple endocrine neoplasia type 2 (MEN-2) is an inherited multiglandular
      disease with age-related penetrance and variable expression. The prognosis of MEN
      2 is linked to the carcinological evolution of medullary thyroid cancer (MTC),
      which depends mainly on the stage of discovery, and to the incidents related to
      pheochromocytomas. The emphasizes the need for early diagnosis and management of
      MEN-2. Since 1993, mutations evidenced on the protooncogene RET have allowed
      subjects at risk to be identified, thus leading to a three-step management of
      these patients. (1) For all the potentially affected members of a MEN-2 family,
      screening by molecular genetics of the ret gene enables one to identify the
      subjects at risk who bear the mutation. When no mutation is observed, a linkage
      analysis study may be proposed. (2) In the subjects at risk, early screening for
      the various types of endocrine lesions may then start in childhood and be
      performed using specific biological markers of MTC, pheochromocytoma and primary
      hyperparathyroidism, and particularly, basal and pentagastrin-stimulated
      calcitonin measurement, which is known to be the most sensitive marker for the
      monitoring of MTC. (3) This step of biological investigations enables the
      earliest possible treatment of any endocrine lesion detected before it is
      expressed clinically, thus improving the prognosis of MEN-2. When genetic
      screening cannot be performed, only annual clinical and biological monitoring
      remain available in all members of a family affected with MEN-2.

PMID- 9167956
TI  - Abnormal transduction mechanisms in pituitary adenomas.
AB  - Pituitary adenomas are differentiated tumors expressing their appropriate mature
      hormone. Tumoral cells sometimes present with a defective physiological
      inhibitory or stimulatory control, resulting in paradoxical responses or
      nonresponsiveness to regulatory neurohormones. These abnormalities can be
      explained by defects at the intracellular transduction mechanism level. Knowledge
      of these defective pathways has made progress in the understanding of the
      pathogenesis of pituitary adenomas possible. The discovery of mutations of Gs
      alpha named gsp oncogenes in 40% of human somatotropinomas represents one of the
      most important advances in this field. Other molecular alterations were
      identified but are rare and sporadic and the pathogenesis of pituitary adenomas
      remains largely unknown. Abnormal transduction mechanisms may also result in a
      variable sensitivity of tumors to pharmacological therapy. The dopamine agonist,
      bromocriptine, is able to normalize blood PRL levels and to reduce tumor size in
      the majority of patients with prolactinoma, but is ineffective in 8-15% of them.
      Under physiological conditions, PRL secretion is under the tonic inhibitory
      control of dopamine which binds D2 receptors negatively coupled to adenylyl
      cyclase. Several defects in the dopaminergic transduction pathways participate in
      this bromocriptine resistance. The mean D2-binding site density is decreased to
      50% as compared to responsive tumors. This loss of D2 receptors can account for a
      lower transcription level of its gene and is accompanied by modifications in the
      messenger alternative splicing; the D2 short isoform receptor expression
      decreases preferentially. A reduction in Gi2 alpha protein expression is also
      observed and is correlated to that of the D2 receptor. Finally, the pituitary
      specific transcription factor Pit-1 expression is affected. A highly significant
      correlation was seen between the D2 receptor mRNA and Pit-1 mRNA levels. These
      defects observed on many levels of the dopaminergic transduction cascade may be
      the first steps in the loss of the functional features of differentiated tumors
      toward more proliferative tumors.

PMID- 9167957
TI  - Cyclic AMP and calcium in the transduction of hypothalamic neurohormone action in
      human pituitary tumors.
AB  - Although hypothalamic neurohormones were originally identified on the basis of
      their ability to influence hormone release from the target cells, it is at
      present clear that these agents are involved in the control of several biological
      processes that include cell proliferation and differentiation as well as
      hyperplasia and neoplastic transformation. Hypothalamic neurohormones bind
      specific receptors belonging to the G-protein-coupled receptor superfamily to
      generate intracellular effectors, in particular cAMP and calcium. Several in vivo
      and in vitro studies suggest the presence of functional and/or structural
      alterations in the receptor/effector molecules involved in the transduction of
      hypothalamic neurohormone action in the pituitary. The present study reports the
      frequent presence in pituitary tumors of cellular alterations that result in
      amplification of stimulatory signals, particularly activation of the cAMP
      dependent pathway, and reduction of inhibitory inputs, both events having
      possible implications in tumor formation and/or progression.

PMID- 9167958
TI  - Nerve growth factor suppresses the tumoral phenotype of human prolactinomas.
AB  - We summarize here our data showing that various phenotypical characteristics
      distinguish prolactinoma cell lines obtained from responder and nonresponder
      patients, as defined by their responses to bromocriptine administration.
      Nonresponder cell lines have a higher degree of malignancy than responder cells
      and do not express D2 receptors for dopamine. Both cell lines express NGF
      receptors. Exposure of the most malignant nonresponder cell lines to NGF, both in
      vitro and when transplanted in vivo in nude mice, results in their
      differentiation into the responder phenotype reexpressing D2 receptors.
      Sequential administration of NGF and bromocriptine thus may be a promising
      therapy for patients refractory to bromocriptine.

PMID- 9167959
TI  - Nuclear effects of the cAMP pathway activation in somatotrophs.
AB  - Activation of the cAMP pathway from the cell surface to the nucleus plays a major
      role in somatotroph differentiation and growth. This pathway is regulated mainly
      by the antagonistic hypothalamic hormones GHRH and somatostatin. Several
      pituitary-specific, as well as ubiquitous, expressed genes are regulated by cAMP
      in GH-secreting cells. Among them are the GH, GHF-1/Pit-1, c-fos and GHRH
      receptor genes. Protein kinase A phosphorylation of Ser 133 of the transcription
      factor cAMP-responsive element binding protein (CREB), seems to play a pivotal
      role in the activation of the cAMP pathway in normal and tumoral somatotrophs.
      The oncogenic activating mutations of the G-protein as subunit stimulate
      transcription and CREB phosphorylation in somatotroph cells. The implications of
      the nuclear targets of cAMP in the differentiation and growth of somatotrophs are
      discussed in this review.

PMID- 9167960
TI  - Pit-1 gene expression in human pituitary adenomas.
AB  - The anterior pituitary-specific transcription factor Pit-1 (also known as GHF-1)
      was initially identified and cloned as a transactivator of the GH and PRL genes,
      and later as a regulator of the TSH beta gene. Analysis of Pit-1 expression
      during mouse embryogenesis revealed that initiation of its expression correlates
      both temporally and spatially with activation of its target genes.
      Immunocytochemical studies revealed a high expression of Pit-1 protein in the
      nuclei of only three cell types: somatotropes, lactotropes and thyrotropes. The
      importance of Pit-1 as a regulator of the anterior pituitary development has been
      further demonstrated by the absence of somatotropes, lactotropes and thyrotropes
      in the pituitary glands of Pit-1-defective mice and humans. Since Pit-1 is
      required for both cell phenotype and proliferation, one may ask if this
      transcription factor might be associated with development of pituitary tumors.
      Several investigators have reported Pit-1 gene expression in human pituitary
      adenomas. These studies, while not in total agreement, show that pituitary
      tumorigenesis does not seem to be associated with a gross alteration of Pit-1
      gene expression in humans. Pit-1 transcripts, identical in size and sequence to
      those observed in normal pituitary, were described in human GH-, PRL- and TSH
      secreting pituitary adenomas and in most cases the presence of Pit-1 transcripts
      correlated with the localization of Pit-1 protein. The biological relevance of
      Pit-1 expression reported in some nonfunctioning adenomas remains to be
      clarified. As expression of the PRL and GH genes is ultimately confined to
      distinct lactotropic and somatotropic populations despite the presence of Pit-1
      protein in both cell types, there must be additional mechanisms that control the
      cell-specific activation of the PRL and GH promoters. The Pit-1 beta isoform,
      raised through alternative splicing of exon 2 of the Pit-1 gene, is a more potent
      inducer of GH transcription than the major Pit-1 form. This form could, at least
      in part, account for the cell-specific activation of the PRL and GH genes. Pit-1
      beta was invariably found present in all the tumors expressing the Pit-1 major
      form, no significant difference in the Pit-1 beta/Pit-1 expression ratio being
      observed between tumors identified as pure GH- or PRL-producing tumors. This lack
      of selectivity together with its low level of expression is therefore not in
      favor of a key role for the beta-isoform in the cell type-specific expression of
      the GH and PRL genes in humans. The failure of somatotropes, lactotropes and
      thyrotropes to proliferate in Pit-1-defective mice and humans indicates that Pit
      1 might be competent to activate genes required for cell proliferation or
      survival of the three cell types. Recent data indeed suggest that Pit-1 may
      directly or indirectly regulate somatotropes and lactotropes through activation
      of the receptors for GRF and SRIF on the one hand, and dopamine on the other
      hand. Such regulatory mechanisms could contribute to the differentiation of the
      somatomammotropic lineage in fully differentiated somatotropic and lactotropic
      cells.

PMID- 9167961
TI  - V3 vasopressin receptor and corticotropic phenotype in pituitary and nonpituitary
      tumors.
AB  - Pituitary corticotropic cells express a specific vasopressin receptor, called V1b
      or V3, through which vasopressin stimulates corticotropin secretion. We recently
      cloned a cDNA coding for this receptor and showed that it belongs to the G
      protein-coupled receptor family. V3 mRNA is readily detected by RT-PCR in normal
      human pituitaries and corticotropic pituitary adenomas but not in PRL or GH
      secreting adenomas, thus demonstrating that, like POMC itself and the CRH
      receptor, V3 is a marker of the corticotropic phenotype. Nuclease protection
      experiments suggest that V3 is overexpressed in some corticotropic adenomas, and
      thus may play a role in tumor development by activating the phospholipase C
      signalling pathway. In addition analysis of its expression in nonpituitary
      neuroendocrine tumors showed a striking association with carcinoids of the lung
      responsible for the ectopic ACTH syndrome.

PMID- 9167962
TI  - Genetic alterations of the RET proto-oncogene in familial and sporadic
      pheochromocytomas.
AB  - The identification of RET proto-oncogene mutations associated with multiple
      endocrine neoplasia type 2 (MEN-2) has provided a convenient screening test for
      MEN-2 in patients with pheochromocytoma (PH). In 120 patients with apparently
      sporadic PH, we analyzed RET exons 10, 11, 13 and 16 using denaturing gradient
      gel electrophoresis and found a Leu to Phe missense mutation at codon 790 (exon
      13) in 1 case. A TaqI polymorphism located at exon 13 and an AluI polymorphism at
      exon 14 were present with a similar frequency in the 120 sporadic PH and in 94
      unaffected normotensive Caucasian subjects. In 60 patients with PH, including 14
      with documented MEN-2, we compared genetic testing with the pentagastrin
      stimulation test. The latter was 100% sensitive and 92% specific, whereas genetic
      testing was 88% sensitive and 100% specific. Additional somatic mutations were
      sought in 35 sporadic PH. Two missense mutations affecting RET exons 11 (C634R)
      and 16 (M918T) and three neutral mutations at codon 836 of exon 14 associated
      with the AluI polymorphism were detected. Detection of RET mutations in patients
      with PH is safe, specific and convenient. Tumoral mutations of the RET gene may
      play a role in medullary tumorigenesis but seem to be less frequent than
      previously reported.

PMID- 9167963
TI  - Molecular markers for malignancy in adrenocortical tumors.
AB  - Little is known about the pathophysiology of sporadic adrenocortical tumors.
      Benign and malignant adrenocortical tumors are often difficult to distinguish by
      conventional histology. We tested 38 adrenocortical tumors (23 benign and 15
      malignant) for loss of heterozygosity (LOH) at 17p13 and abnormalities in the
      11p15 region (uniparental disomy, UPD, and overexpression of the IGF II gene). We
      showed that 17p13 LOH, 11p15 UPD and overexpression of the IFG II gene are
      frequent in adrenocortical tumors, occurring in 40% of them. These genetic
      changes are associated with the malignant phenotype and thus could be used for
      diagnostic evaluation of adrenocortical tumors.

PMID- 9167964
TI  - Adrenocorticotropin receptor and adrenal disorders.
AB  - The ACTH receptor is the shortest G-protein-coupled receptor to date and consists
      of 297 residues with two putative glycosylation sites at the extracellular N
      terminus. In vitro studies have demonstrated upregulation of the ACTH receptor by
      its own ligand and by angiotensin II. Inactivating mutations of the ACTH receptor
      lead to the familial glucocorticoid deficiency (FGD) syndrome, a rare recessive
      autosomal disorder characterized by degeneration of the zona
      fasciculata/reticularis and unresponsiveness to exogenous ACTH. Interestingly,
      ACTH receptor mutations are not present in all patients with FGD and also not in
      the closely related "triple A' syndrome indicating that other mechanisms of ACTH
      resistance are still to be elucidated. Despite an extensive search, no activating
      ACTH receptor mutations have been found in adrenal tumors, excluding the ACTH
      receptor as a relevant oncogene for adrenal tumorigenesis. However, the ACTH
      receptor may play a role as a differentiation factor, as loss of heterozygosity
      for the ACTH receptor in adrenal tumors seems to be associated with an
      undifferentiated phenotype. ACTH receptor mRNA expression in benign adrenal
      tumors is strongly related to the expression of P-450 side chain cleavage enzyme
      mRNA indicating a close regulative relationship. However, this correlation is
      disrupted in adrenal carcinomas, an observation which may help in the difficult
      differential diagnosis between benign and malignant tumors. Surprisingly, the
      highest ACTH receptor mRNA expression was found in aldosteronomas, while it is
      low in non-functioning adenomas and carcinomas. No correlation between ACTH
      receptor mRNA expression and circulating ACTH levels has been found in patients
      with adrenal disorders casting doubts on the physiological significance of ACTH
      receptor upregulation by its own ligand in vivo.

PMID- 9167965
TI  - Adrenal incidentaloma: an overview of clinical and epidemiological data from the
      National Italian Study Group.
AB  - BACKGROUND: The incidental discovery of an adrenal mass raises the problem of
      distinguishing the frequent benign masses from the infrequent malignant ones that
      require surgery. At present, univocal guidelines to approach this problem are not
      available. The aim of the present study was to perform a multicentric
      retrospective analysis of adrenal masses incidentally discovered (adrenal
      incidentalomas). PATIENTS AND METHODS: Hospital records of adrenal incidentalomas
      diagnosed over a 15-year period in 29 surgical and medical centers in Italy were
      scrutinized. Collected cases were 1,013, and 887 were analyzed. RESULTS: The
      majority of patients were in the 5th and 6th decade and females were
      predominantly affected. The frequency of adrenocortical cancer was 12% among
      operated patients (316 cases). The tumor diameter was highly correlated with the
      risk of malignancy, as well as the CT characteristics such as density, shape and
      margins. The frequency of pheochromocytoma was 10% among operated patients.
      CONCLUSIONS: The occurrence of incidentally discovered adrenocortical carcinomas
      and pheochromocytomas is not rare. Evaluation of the mass size and CT
      characteristics are simple and effective methods to differentiate malignant
      lesions. Biochemical screening for pheochromocytoma is mandatory before surgery.

PMID- 9167966
TI  - Adrenal incidentaloma: an overview of hormonal data from the National Italian
      Study Group.
AB  - Adrenal masses are more and more frequently detected by adrenal ultrasound,
      computed tomography or nuclear magnetic resonance carried out for a reason other
      than the suspicion of adrenal disease (incidentalomas). The findings of an
      incidentaloma still leaves many diagnostic and therapeutic questions open. We
      report the results of a multicentric retrospective evaluation of patients with
      adrenal incidentalomas, performed by a Study Group of the Italian Society of
      Endocrinology. According to the definition of incidentaloma, exclusion criteria a
      priori were: severe or paroxysmal hypertension, frank hypokalemia and clinical
      signs of hypercortisolism or hyperandrogenism. 29 centers participated in the
      study and the data obtained by questionnaire were collected in 2 centers for
      final elaboration. Center 1 carried out the epidemiological and clinical
      evaluation. Basal and dynamic hormonal evaluation of 786 among the 1013 cases
      recruited were performed in our center (center 2). Functional studies included:
      diurnal rhythm of cortisol, urinary free cortisol (UFC), ACTH, DHEAS, 17-OH
      progesterone, testosterone, androstenedione, supine and upright plasma renin
      activity (PRA) and aldosterone, urinary aldosterone, urinary catecholamines and
      VMA. The hormonal dynamic evaluation included the overnight dexamethasone
      suppression test (1 mg), CRH test and ACTH test. In our study, 89% (702 patients)
      of adrenal incidentalomas were non-hypersecretory masses; 6.2% (49 patients)
      showed a preclinical Cushing's syndrome (PCS) (at least two altered parameters of
      pituitary-adrenal axis); 3.4% (27 patients) were pheochromocytomas; 0.89% (7
      patients) were aldosteronomas. One tumor was a masculinizing adrenocortical
      carcinoma. Two hundred sixty patients underwent surgical exploration and the
      histological diagnosis showed: 138 adenomas (53%), 32 carcinomas (12%), 26
      pheochromocytomas (10%). 16 myelolipomas (8%), 13 cystic lesions (5.5%), 7 tumors
      of neuronal lineage (3%). 12 metastases (4%), 13 others (5%). The 138 patients
      with adenomas had the following hormonal diagnosis: 103 nonfunctional adenomas
      (74%), 31 PCS (23%) and 4 cases of hyperaldosteronism (3%). In the patients with
      PCS an abnormal dexamethasone suppression test was found in 86% of cases (37/41
      patients). Values for ACTH were low in 78% (32/41 patients). UFC was elevated in
      64% of patients, the diurnal rhythm of cortisol evaluated in 14 patients was
      absent in 7. Only in 50% of cases DHEAS values (12/24 patients) were decreased,
      whereas they were normal in the other 50%. Interestingly, 8 patients with normal
      DHEAS and normal UFC showed nonsuppressible cortisol by dexamethasone test (1
      mg). Blunted ACTH response to CRH was detected in 9 of 14 patients (64%). Thus
      our data suggest that the best parameter for evaluating subclinical
      hypercortisolism seems to be the overnight dexamethasone suppression test. In 27
      patients with pheochromocytoma 24-hour urinary catecholamine and VMA levels were
      elevated in 86 and 46% of cases respectively. In 7 patients with
      hyperaldosteronism upright PRA was suppressed in 100% of cases and aldosterone
      plasma levels were elevated in 6 patients (86%); serum potassium level was
      slightly decreased in 60% of cases. In 86 of 138 histologically proven adenomas,
      DHEAS levels were: normal in 59% of patients, decreased in 36% and elevated in
      4.6%, whereas in 22 of 32 cortical carcinomas evaluated. DHEAS levels were normal
      in 63% of cases, decreased in 18% and elevated 18%. Post-ACTH 17-OH progesterone
      levels were elevated in 52% (62/118 patients) of non-functioning adenomas and in
      2 of 4 carcinomas. Not enough data are yet available postoperatively. In summary,
      endocrine evaluation can lead to the identification of a nonnegligible number of
      cases of clinically unsuspected pheochromocytomas and subtle hypercortisolism
      (about 3.4 and 6.2%, respectively of all adrenal incidentalomas), while cases of
      primary subclinical aldosteronism are rarely found. (ABSTRACT TRUNCATED)

PMID- 9167967
TI  - The ontogenesis of the steroidogenic tissues.
AB  - Based on the common function of steroid hormone-producing tissues and homologous
      regulation by the hypothalamo-pituitary axis, the adrenal cortex and the gonads
      have been suggested to have an intimate ontogenic relationship. This assumption
      is also supported by the findings of common transcription factors implicated in
      the differentiation of both types of tissue and further supported by concomitant
      defects in such tissues due to the disruption of a single gene. Similarly,
      simultaneous anomalies in those tissues are also observed in some diseases caused
      by mutations of the genes encoding those transcription factors. A recent
      immunohistochemical study with one of the transcription factors, Ad4BP/SF-1,
      definitely demonstrated the presence of a particular cell population designated
      the 'adreno-genital primordium (AGP)' which gives rise to both the adrenal cortex
      and the gonads. In the process of differentiation from the AGP to the mature
      adrenal cortex and the gonads of the two sexes, several interesting issues can be
      raised as to the next targets for the study. To address these issues it is
      important to elucidate the upstream regulatory mechanisms and downstream target
      genes of such transcription factors as WT1, SRY, SOX9 and DAX1, in addition to
      Ad4BP/SF-1, all of which are implicated in steroidogenic tissue differentiation.

PMID- 9167968
TI  - Upstream and downstream of erythroid transcription factor GATA-1.
AB  - All mature blood lineages in the peripheral circulation are derived from
      pluripotent haematopoietic stem cell. Progressive lineage-restriction of this
      stem cell is executed, in part, by the interplay and cross-talk between a host of
      lineage-restricted as well as ubiquitous transcription factors. To elucidate the
      regulatory mechanisms underlying the erythroid gene regulation, it is essential
      to understand how individual transcription factors contribute to the regulation
      of specific target genes, and how these erythroid transcription factor genes are
      regulated in turn. These key issues of mammalian development have been addressed
      by examining the activities controlling the prototype transcription factor, GATA
      1. The transcriptional regulation of GATA-1 has been intensively investigated,
      thereby leading to the identification of its developmental stage-specific
      regulatory sequences. Loss-of-function mutant animals, combined with specific
      marking of the primitive and definitive erythroid lineages have also shed new
      insight into how GATA-1 activity is required in vivo at specific developmental
      stages. Procedures have also been developed for ascertaining whether or not the
      GATA-1 protein actually binds in vivo to regulatory GATA motifs in candidate
      target genes. Application of a similar multifaceted approach should enable
      investigators to examine the physiological roles that any transcription factor
      might play in vivo during the differentiation of any well defined cell lineage.

PMID- 9167969
TI  - Chi-activated RecBCD enzyme possesses 5'-->3' nucleolytic activity, but RecBC
      enzyme does not: evidence suggesting that the alteration induced by Chi is not
      simply ejection of the RecD subunit.
AB  - BACKGROUND: Homologous recombination in Escherichia coli is initiated by the
      RecBCD enzyme, and is stimulated by DNA elements known as Chi (chi) sites. The
      RecBCD enzyme is both a helicase and a nuclease. Recognition of chi causes both
      attenuation of the 3'-->5' exonuclease activity of the RecBCD enzyme, and
      activation of an exonuclease activity with 5'-->3' polarity, while leaving the
      helicase activity unaffected. A variety of evidence suggests that chi-recognition
      by RecBCD enzyme is accompanied by ejection of the RecD subunit. RESULTS: Through
      examination of RecBCD exonuclease activity under a variety of conditions, we have
      shown that recognition of chi by the RecBCD enzyme results in a net reduction of
      nuclease activity. In addition, the exact location of the first cleavage event
      elicited by chi-activation of the 5'-->3' nuclease is dependent upon the
      concentration of free magnesium ions. Finally, we have demonstrated that purified
      RecBC enzyme (i.e. without the RecD subunit) possesses no significant exonuclease
      activity under conditions where the chi-modified RecBCD enzyme is an active 5'-
      >3' exonuclease. CONCLUSIONS: We have shown that, despite the activation of a 5'-
      >3' exonuclease, recognition of chi by the RecBCD enzyme results in a net
      preservation of DNA. This new chi-activated nucleolytic action shows surprising
      variability in the exact location of its initial cleavage. We have demonstrated
      that purified RecBC enzyme is not an exact analogue of the chi-activated RecBCD
      enzyme, suggesting that the biochemical basis of chi-activation is not simply
      ejection of the RecD subunit.

PMID- 9167970
TI  - The highly conserved DAD1 protein involved in apoptosis is required for N-linked
      glycosylation.
AB  - BACKGROUND: The tsBN7 cell line is one of the temperature-sensitive mutants for
      cell proliferation which have been isolated from the BHK21 cell line derived from
      the golden hamster. It has a mutation in the DAD1 gene encoding a 12.5kDa highly
      conserved protein through evolution, and enters apoptosis at the restrictive
      temperature due to this mutation. RESULTS: DAD1 was recovered in light membrane
      fractions after differential centrifugation. It could not be released from the
      membrane, even by carbonate extraction, without a detergent. Upon digestion with
      proteinase K, both N and C terminal portions-but not the middle portions of DAD1-
      were released from the membrane. Thus, DAD1 appears to be an integral membrane
      protein in which both termini are located in the cytosol. DAD1 was localized in
      the endoplasmic reticulum. In accordance with a similarity to the yeast protein
      Ost2p, which is a subunit of the oligosaccharyltransferase, at the restrictive
      temperature, loss of DAD1 function caused a defect of N-linked glycosylation in
      tsBN7 cells resulting in apoptosis. However, tunicamycin, which is known to
      inhibit N-linked glycosylation did not induce apoptosis in either tsBN7 or BHK21
      cells. CONCLUSION: tsBN7 cells have a defect in N-linked glycosylation caused by
      the loss of DAD1.

PMID- 9167971
TI  - Transcriptional activation through interaction of MBF2 with TFIIA.
AB  - BACKGROUND: Transcriptional activation of the Drosopohila melanogaster fushi
      tarzu gene by FTZ-F1 or its silkworm counterpart BmFTZ-F1 requires two cofactors
      MBF1 and MBF2 which do not directly bind to DNA. MBF1 is a bridging molecule that
      connects FTZ-F1 (or BmFTZ- F1), MBF2 and TATA binding protein TBP. MBF2 is a
      positive cofactor that activates transcription. RESULTS: To elucidate the
      mechanism of transcriptional activation by MBF2, we isolated a cDNA coding for
      the factor. Northern blot analyses showed temporally restricted expression of
      MBF2 mRNA similar to that of BmFTZ-F1 mRNA. The cDNA sequence predicts a
      polypeptide of 10 kDa whereas natural MBF2 is a glycoprotein of 22 kDa. The
      deduced amino acid sequence of the factor showed no homology with proteins in the
      databases. Farwestern analyses and glutathione S-transferase interaction assays
      demonstrated that MBF2 makes a direct contact with the beta-subunit of TFIIA. In
      a HeLa cell nuclear extract, bacterially expressed recombinant MBF2 activated
      transcription from various promoters as natural MBF2 did. This activation
      requires the MBF2-TFIIA interaction. When recombinant MBF2 was added to the HeLa
      cell nuclear extract in the presence of MBF1 and FTZ622 bearing the DNA-binding
      region of FTZ-F1, it selectively activated transcription of the fushi tarazu
      gene. This selective activation also requires the MBF2-TFIIA interaction.
      CONCLUSION: MBF2 activates transcription through its interaction with TFIIA.
      Selective transcriptional activation occurs when MBF2 is recruited to a promoter
      carrying the FTZ-F1 binding site by FTZ-F1 and MBF1.

PMID- 9167972
TI  - Microtubule-associated coiled-coil protein Ssm4 is involved in the meiotic
      development in fission yeast.
AB  - BACKGROUND: In fission yeast, an RNA species named meiRNA is specifically
      required for the promotion of the first meiotic division. To dissect the function
      of this RNA and its partner RNA-binding protein Mei2, we screened for high-copy
      number suppressors of the arrest prior to the first meiotic division caused by
      loss of meiRNA. RESULTS: Analysis of one of the suppressors, named ssm4,
      suggested that it encodes a coiled-coil protein carrying a microtubule-binding
      motif at its N-terminus. Expression of ssm4 was restricted to cells undergoing
      meiosis. Disruption of ssm4 affected neither vegetative growth nor conjugation,
      but resulted in frequent generation of asci carrying less than four spores.
      Tagged Ssm4 could colocalize with microtubules in mitotic cells, and was seen to
      localize at spindles during both the first and the second meiotic division. The
      microtubule-binding motif was essential for the association of Ssm4 with
      microtubules and for its function during meiosis, but not for the suppression of
      loss of meiRNA. Ssm4 appeared to possess a potential to migrate to the nucleus.
      CONCLUSIONS: Ssm4 is a microtubule-colocalizing protein that plays a role
      specifically in meiosis. Ssm4 appears to modify the structure or the function of
      nuclear microtubules in order to promote the meiotic nuclear division.

PMID- 9167973
TI  - Experimental approaches to chemical sensitivity: introduction and overview.

PMID- 9167974
TI  - Chemical sensitivity: the scientific literature.
AB  - This article provides an overview of the scientific literature in which
      chemically sensitive patients have been directly evaluated. For that purpose,
      consideration of various case definitions is offered along with summaries of
      subjects' demographic profiles, exposure characteristics, and symptom profiles
      across studies. Controlled investigations of chemically sensitive subjects
      without other organic illnesses are reviewed. To date, psychiatric, personality,
      cognitive/neurologic, immunologic, and olfactory studies have been conducted
      comparing subjects with primary chemical sensitivity to various control groups.
      Thus far, the most consistent finding is that chemically sensitive patients have
      a higher rate of psychiatric disorders across studies and relative to diverse
      comparison groups. However, since these studies are cross-sectional, causality
      cannot be implied. Demonstrating the role of low-level chemical exposure in a
      controlled environment has yet to be undertaken with this patient group and is
      crucial to the understanding of this phenomenon.

PMID- 9167975
TI  - Profile of patients with chemical injury and sensitivity.
AB  - Patients reporting sensitivity to multiple chemicals at levels usually tolerated
      by the healthy population were administered standardized questionnaires to
      evaluate their symptoms and the exposures that aggravated these symptoms. Many
      patients were referred for medical tests. It is thought that patients with
      chemical sensitivity have organ abnormalities involving the liver, nervous system
      (brain, including limbic, peripheral, autonomic), immune system, and porphyrin
      metabolism, probably reflecting chemical injury to these systems. Laboratory
      results are not consistent with a psychologic origin of chemical sensitivity.
      Substantial overlap between chemical sensitivity, fibromyalgia, and chronic
      fatigue syndrome exists: the latter two conditions often involve chemical
      sensitivity and may even be the same disorder. Other disorders commonly seen in
      chemical sensitivity patients include headache (often migraine), chronic fatigue,
      musculoskeletal aching, chronic respiratory inflammation (rhinitis, sinusitis,
      laryngitis, asthma), attention deficit, and hyperactivity (affected younger
      children). Less common disorders include tremor, seizures, and mitral valve
      prolapse. Patients with these overlapping disorders should be evaluated for
      chemical sensitivity and excluded from control groups in future research. Agents
      whose exposures are associated with symptoms and suspected of causing onset of
      chemical sensitivity with chronic illness include gasoline, kerosene, natural
      gas, pesticides (especially chlordane and chlorpyrifos), solvents, new carpet and
      other renovation materials, adhesives/glues, fiberglass, carbonless copy paper,
      fabric softener, formaldehyde and glutaraldehyde, carpet shampoos (lauryl
      sulfate) and other cleaning agents, isocyanates, combustion products (poorly
      vented gas heaters, overheated batteries), and medications (dinitrochlorobenzene
      for warts, intranasally packed neosynephrine, prolonged antibiotics, and general
      anesthesia with petrochemicals). Multiple mechanisms of chemical injury that
      magnify response to exposures in chemically sensitive patients can include
      neurogenic inflammation (respiratory, gastrointestinal, genitourinary), kindling
      and time-dependent sensitization (neurologic), impaired porphyrin metabolism
      (multiple organs), and immune activation.

PMID- 9167976
TI  - Clinical characteristics of chemical sensitivity: an illustrative case history of
      asthma and MCS.
AB  - A case history of the induction of asthma and chemical sensitivity in a 42-year
      old registered nurse illustrates several of the characteristic features of
      multiple chemical sensitivity (MCS). This patient's problems started shortly
      after moving into a new home under construction, with associated chemical
      exposures. Other MCS patients report the onset of the condition with other
      chemical exposures such as those encountered at their places of work or use of
      pesticides at their residences. Patients often describe a spreading phenomenon of
      increasing intolerance to commonly encountered chemicals at concentrations well
      tolerated by other people. Symptoms usually wax and wane with exposures, and are
      more likely to occur in patients or families with preexisting histories of
      migraine or with classical allergies. Idiosyncratic medication reactions
      (especially to preservative chemicals) are common in MCS patients, as are
      dysautonomia symptoms (such as vascular instability) and poor temperature
      regulation. Myalgia and joint pains and food intolerance are common features as
      well. Contamination with xenobiotic chemicals is frequently found in these
      patients when they are tested. Reactive airways dysfunction syndrome is a
      recently identified condition that exhibits features of both asthma and chemical
      sensitivity. MCS patients frequently have patterns of neurotoxic brain metabolism
      that can be confirmed on single photo emission computed tomography imaging.

PMID- 9167977
TI  - Laboratory testing of the patient with multiple chemical sensitivity.
AB  - Multiple diagnostic laboratory tests are frequently used in the clinical
      evaluation of persons with multiple chemical sensitivity without a clear a priori
      hypothesis. In addition, many of these tests are performed despite a lack of
      understanding of the test technical performance characteristics or the clinical
      significance (test sensitivity and specificity). The result is a plethora of
      laboratory data that have little clinical relevance and that can be both
      misleading and misused.

PMID- 9167978
TI  - Toxicant-induced loss of tolerance--an emerging theory of disease?
AB  - This paper attempts to clarify the nature of chemical sensitivity by proposing a
      theory of disease that unites the disparate clinical observations associated with
      the condition. Sensitivity to chemicals appears to be the consequence of a two
      step process: loss of tolerance in susceptible persons following exposure to
      various toxicants, and subsequent triggering of symptoms by extremely small
      quantities of previously tolerated chemicals, drugs, foods, and food and drug
      combinations including caffeine and alcohol. Although chemical sensitivity may be
      the consequence of this process, a term that may more clearly describe the
      observed process is toxicant-induced loss of tolerance. Features of this yet-to
      be-proven mechanism or theory of disease that affect the design of human exposure
      studies include the stimulatory and withdrawallike nature (resembling addiction)
      of symptoms reported by patients and masking. Masking, which may blunt or
      eliminate responses to chemical challenges, appears to have several components:
      apposition, which is the overlapping of the effects of closely timed exposures,
      acclimatization or habituation, and addiction. A number of human challenge
      studies in this area have concluded that there is no physiological basis for
      chemical sensitivity. However, these studies have failed to address the role of
      masking. To ensure reliable and reproducible responses to challenges, future
      studies in which subjects are evaluated in an environmental medical unit, a
      hospital-based facility in which background chemical exposures are reduced to the
      lowest levels practicable, may be necessary. A set of postulates is offered to
      determine whether there is a causal relationship between low-level chemical
      exposures and symptoms using an environmental medical unit.

PMID- 9167979
TI  - Evolving concepts of chemical sensitivity.
AB  - Chemical sensitivity appears to be an elusive phenomenon. Studies on individual
      differences in susceptibility may provide glimpses into the range of sensitivity
      in a population, which can be used for further study. Preliminary evidence in
      laboratory animals suggests the range of sensitivity to manufactured chemicals
      may span orders of magnitude. Determining the reasons that underlie individual
      differences in sensitivity is a more difficult enterprise. Conditioning of
      adverse physiological effects of airborne chemicals may play a vital role in the
      etiology of chemical sensitivity, and it provides a rigorous laboratory model by
      which to investigate some aspects of this elusive phenomenon.

PMID- 9167980
TI  - Individual differences in neural sensitization and the role of context in illness
      from low-level environmental chemical exposures.
AB  - This paper summarizes the clinical phenomenology of multiple chemical sensitivity
      (MCS), outlines the concepts and evidence for the olfactory-limbic, neural
      sensitization model for MCS, and discusses experimental design implications of
      the model for exposure-related research. Neural sensitization is the progressive
      amplification of responsivity by the passage of time between repeated,
      intermittent exposures. Initiation of sensitization may require single toxic or
      multiple subtoxic exposures, but subsequent elicitation of sensitized responses
      can involve low or nontoxic levels. Thus, neural sensitization could account for
      the ability of low levels of environmental chemicals to elicit clinically severe,
      adverse reactions in MCS. Different forms of sensitization include limbic
      kindling of seizures (compare temporal lobe epilepsy and simple partial seizures)
      and time-dependent sensitization of behavioral, neurochemical, immunological, and
      endocrinological variables. Sensitized dysfunction of the limbic and mesolimbic
      systems could account in part for many of the cognitive, affective, and somatic
      symptoms in MCS. Derealization (an alteration in perception making familiar
      objects or people seem unfamiliar or unreal) is a common MCS symptom and has been
      linked with limbic dysfunction in clinical neuroscience research. Sensitization
      is distinct from, but interactive with, other neurobiological learning and memory
      processes such as conditioning and habituation (compare adaptation or tolerance).
      In previous studies, hypotheses for MCS involving sensitization, conditioning,
      and habituation (adaptation) have often been considered in isolation from one
      another. To design more appropriate chemical exposure studies, it may be
      important to integrate the various theoretical models and empirical approaches to
      MCS with the larger scientific literature on individual differences in these
      potentially interactive phenomena.

PMID- 9167981
TI  - Potential role of stress and sensitization in the development and expression of
      multiple chemical sensitivity.
AB  - Chemical sensitivity in humans may be an acquired disorder in which individuals
      become increasingly sensitive to chemicals in the environment. It is hypothesized
      that in individuals with multiple chemical sensitivity (MCS), a sensitization
      process has occurred that is akin to behavioral sensitization and kindling
      observed in rodents. In the rodent sensitization model, repeated exposure to
      stress or drugs of abuse enhances behavioral and neurochemical responses to
      subsequent stimuli (stress or drugs of abuse). Kindling is a form of
      sensitization in which repeated application of electrical stimuli applied to the
      brain at low levels culminates in the induction of full-blown seizures when the
      same stimulus is applied at a later time. A similar sensitization of specific
      limbic pathways in the brain may occur in individuals with MCS. The time
      dependent nature of sensitization and kindling and the role of stress in the
      development of sensitization are discussed in the context of rodent models, with
      an emphasis on application of these models to human studies of MCS.

PMID- 9167982
TI  - Hypothesis for induction and propagation of chemical sensitivity based on biopsy
      studies.
AB  - The reactive airways dysfunction syndrome (RADS), the reactive upper airways
      dysfunction syndrome (RUDS), the sick building syndrome (SBS), and the multiple
      chemical sensitivity syndrome (MCS) are overlapping disorders in which there is
      an intolerance to environmental chemicals. The onset of these illnesses is often
      associated with an initial acute chemical exposure. To understand the
      pathophysiology of these conditions, a study of the nasal pathology of
      individuals experiencing these syndromes was undertaken. Preliminary data
      indicate that the nasal pathology of these disorders is characterized by defects
      in tight junctions between cells, desquamation of the respiratory epithelium,
      glandular hyperplasia, lymphocytic infiltrates, and peripheral nerve fiber
      proliferation. These findings suggest a model for a relationship between the
      chronic inflammation seen in these conditions and an individual's sensitivity to
      chemicals. A positive feedback loop is set up: the inflammatory response to low
      levels of chemical irritants is enhanced due to the observed changes in the
      epithelium, and the epithelial changes are propagated by the inflammatory
      response to the chemicals. This model, combined with the concept of neurogenic
      switching, has the potential to explain many aspects of RADS, RUDS, SBS, and MCS
      in a unified way.

PMID- 9167983
TI  - Psychophysiological hypotheses regarding multiple chemical sensitivity syndrome.
AB  - This paper proposes several hypotheses and research strategies for exploring
      possible psychological factors contributing to multiple chemical sensitivity
      (MCS). The hypotheses are based on concepts of individual response stereotypy,
      situational response specificity, classical conditioning of chemical-induced
      responses, and psychophysiological reactions to active and passive coping
      orientations. Hypotheses regarding hypersensitivity to perception and/or
      aversiveness of chemical stimulation also are presented. Strategies for
      evaluating these hypotheses are described based on experimental literature on
      psychophysiology and psychophysics.

PMID- 9167984
TI  - Systematic considerations in the area of multiple chemical sensitivity.
AB  - Many workers who speculate about multiple chemical sensitivity (MCS) have devised
      a large number of hypothetical constructs designed to explain the phenomena. Too
      often these are not logically connected to the larger body of scientific thought
      but instead appeal to ideas not documented in accessible literature and often
      appearing metaphysical in nature.

PMID- 9167985
TI  - Experimental strategies for research on multiple chemical sensitivity.
AB  - Skepticism about the validity of the multiple chemical sensitivity (MCS) syndrome
      stems in part from the lack of supporting experimental data. Performing the
      relevant experiments requires investigators to take account of broad variations
      in sensitivity and the need to establish reproducibility. The research approach
      best suited for MCS studies is the single-subject design. In contrast with
      conventional group designs, such designs emphasize repeated observations on
      individual subjects. Repeated observations of this kind constitute a time series
      in which successive measurements are serially or autocorrelated. One statistical
      method that bypasses the serial correlation problem is randomization tests.
      Explicit time series analyses take account of this aspect and can correct for it
      to determine the impact of an intervention such as a chemical exposure.

PMID- 9167986
TI  - Cognitive and psychomotor performance tests and experiment design in multiple
      chemical sensitivity.
AB  - People suffering from multiple chemical sensitivity (MCS) complain of a variety
      of symptoms that could impair cognitive and psychomotor function either directly
      or indirectly. This paper discusses the use of cognitive and psychomotor
      performance tests together with some experiment designs that could be considered
      for use to assess fitness of MCS sufferers for work or the efficacy of
      diagnostic, preventative, or therapeutic measures. The tests could also
      contribute to the body of objective information on MCS and help sway the opinion
      of those who are dubious of its authenticity. The credentials of cognitive and
      psychomotor performance tests are derived from their successful use in studying
      the effects of drugs, and the types of tests are illustrated by describing those
      used by the United Kingdom Defence Evaluation and Research Agency Chemical and
      Biological Defence Human Studies Group, which has been involved in the assessment
      of drugs and chemicals on work performance for many years. The tests include
      mathematical, verbal and spatial processing, tracking, reaction time, attention
      and vigilance, and memory tests. The discussion of experiment designs includes
      both repeated measures and parallel groups designs together with their advantages
      and disadvantages and some suggested modifications to accommodate the particular
      problems posed by MCS.

PMID- 9167987
TI  - A behavior-genetic approach to multiple chemical sensitivity.
AB  - This report emphasizes the application of behavior-genetic designs to the study
      of sensitivity to toxic chemicals, and features of multiple chemical sensitivity
      and substance abuse that are polar opposites. The implications of these issues
      for future research are discussed in relation to twin, adoption, and sibling pair
      studies, as well as in relation to the degree to which genetically selected lines
      of rodents that have been developed in the alcoholism field are applicable to
      multiple chemical sensitivity.

PMID- 9167988
TI  - Human drug discrimination and multiple chemical sensitivity: caffeine exposure as
      an experimental model.
AB  - Multiple chemical sensitivity is a controversial diagnosis. Rigorous, controlled,
      laboratory-based research can reduce this controversy and lead to potential
      clinical confirmatory tests. The literature on human caffeine discrimination
      provides a rigorous methodology that can address reports that patients who suffer
      multiple chemical sensitivity (MCS) are sensitive to usually well-tolerated
      chemical doses; the studies require patients to discriminate caffeine from
      placebo under double-blind conditions. Several issues relevant to the conduct of
      caffeine discrimination studies using MCS patients as subjects are addressed;
      these issues include study design, determination of safe and tolerable training
      doses, and discrimination training. Such research will benefit patients and
      clinicians dealing with a diagnosis of MCS.

PMID- 9167989
TI  - Empirical approaches for the investigation of toxicant-induced loss of tolerance.
AB  - It has been hypothesized that sensitivity to low-level chemical exposures
      develops in two steps: initiation by an acute or chronic chemical exposure,
      followed by triggering of symptoms by low levels of previously tolerated chemical
      inhalants, foods, or drugs. The Working Group on Toxicant-induced Loss of
      Tolerance has formulated a series of research questions to test this hypothesis:
      Do some individuals experience sensitivity to chemicals at levels of exposure
      unexplained by classical toxicological thresholds and dose-response
      relationships, and outside normally expected variation in the population? Do
      chemically sensitive subjects exhibit masking that may interfere with the
      reproducibility of their responses to chemical challenges? Does chemical
      sensitivity develop because of acute, intermittent, or continuous exposure to
      certain substances? If so, what substances are most likely to initiate this
      process? An experimental approach for testing directly the relationship between
      patients' reported symptoms and specific exposures was outlined in response to
      the first question, which was felt to be a key question. Double-blind, placebo
      controlled challenges performed in an environmentally controlled hospital
      facility (environmental medical unit) coupled with rigorous documentation of both
      objective and subjective responses are necessary to answer this question and to
      help elucidate the nature and origins of chemical sensitivity.

PMID- 9167990
TI  - Pavlovian conditioning and multiple chemical sensitivity.
AB  - Pavlovian conditioning processes may contribute to some symptoms of multiple
      chemical sensitivity (MCS). This review summarizes the potential relevance of the
      literature on conditional taste and olfactory aversions, conditional
      sensitization, and conditional immunomodulation to understanding MCS. A
      conditioning-based perspective on MCS suggests novel research and treatment
      strategies.

PMID- 9167991
TI  - Psychoneuroimmunology.
AB  - This paper develops hypotheses regarding the interactions among stress, immunity,
      and chemical sensitivities and gives an overview of the questions and hypotheses
      generated by a working group exploring the application of psychoneuroimmunology
      to chemical sensitivities. Consideration is given to prospective longitudinal
      studies designed to find cases among at-risk exposed populations. Relevant immune
      parameters to be measured longitudinally and in challenge studies for patients
      with MCS are discussed. Immune system changes in response to the chronic stress
      of having MCS and as primary responses to chemical exposure also are considered.

PMID- 9167992
TI  - Neurogenic inflammation: with additional discussion of central and perceptual
      integration of nonneurogenic inflammation.
AB  - The Working Group on Neurogenic Inflammation proposed 11 testable hypotheses in
      the three domains of neurogenic inflammation, perceptual and central integration,
      and nonneurogenic inflammation. The working group selected the term people
      reporting chemical sensitivity (PRCS) to identify the primary subject group. In
      the domain of neurogenic inflammation, testable hypotheses included: PRCS have an
      increased density of c-fiber neurons in symptomatic tissues; PRCS produce greater
      quantities of neuropeptides and prostanoids than nonsensitive subjects in
      response to exposure to low-level capsaicin or irritant chemicals; PRCS have an
      increased and prolonged response to exogenously administered c-fiber activators
      such as capsaicin; PRCS demonstrate augmentation of central autonomic reflexes
      following exposure to agents that produce c-fiber stimulation; PRCS have
      decreased quantities of neutral endopeptidase in their mucosa; exogenous
      neuropeptide challenge reproduces symptoms of PRCS. In the domain of perceptual
      and central integration, testable hypotheses included: PRCS have alterations in
      adaptation, habituation, cortical representation, perception, cognition, and
      hedonics compared to controls; the qualitative and quantitative interactions
      between trigeminal and olfactory systems are altered in PRCS; higher integration
      of sensory inputs is altered in PRCS. In the domain of nonneurogenic
      inflammation, testable hypotheses included: increased inflammation is present in
      PRCS in symptomatic tissues and is associated with a heightened neurosensory
      response; PRCS show an augmented inflammatory response to chemical exposure. The
      working group recommended that studies be initiated in these areas.

PMID- 9167994
TI  - Hormones, hormone metabolism, environment, and breast cancer: a workshop of the
      National Action Plan on Breast Cancer's Etiology Working Group.

PMID- 9167993
TI  - Testing the neural sensitization and kindling hypothesis for illness from low
      levels of environmental chemicals.
AB  - Sensitization in the neuroscience and pharmacology literatures is defined as
      progressive increase in the size of a response over repeated presentations of a
      stimulus. Types of sensitization include stimulant drug-induced time-dependent
      sensitization (TDS), an animal model related to substance abuse, and limbic
      kindling, an animal model for temporal lobe epilepsy. Neural sensitization
      (primarily nonconvulsive or subconvulsive) to the adverse properties of
      substances has been hypothesized to underlie the initiation and subsequent
      elicitation of heightened sensitivity to low levels of environmental chemicals. A
      corollary of the sensitization model is that individuals with illness from low
      level chemicals are among the more sensitizable members of the population. The
      Working Group on Sensitization and Kindling identified two primary goals for a
      research approach to this problem: to perform controlled experiments to determine
      whether or not sensitization to low-level chemical exposures occurs in multiple
      chemical sensitivity (MCS) patients; and to use animal preparations for kindling
      and TDS as nonhomologous models for the initiation and elicitation of MCS.

PMID- 9167995
TI  - Estradiol metabolism: an endocrine biomarker for modulation of human mammary
      carcinogenesis.
AB  - The natural estrogen 17beta-estradiol (E2) has a profound influence on
      proliferation and neoplastic transformation of mammary epithelium. The role of
      cellular metabolism of E2 in mammary carcinogenesis, however, remains to be
      elucidated. Explant culture and cell culture models developed from noncancerous
      human mammary tissue were used to examine modulation of E2 metabolism in response
      to treatment with prototype rodent mammary carcinogens and the ability of the
      naturally occurring phytochemical indole-3-carbinol (13C) to influence E2
      metabolism and regulate aberrant proliferation. In the two models, treatment with
      the chemical carcinogens 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene
      altered the metabolism of E2 as determined from the radiometric (tritium release)
      and gas chromatography-mass spectrometry (GC-MS) assays. This alteration in E2
      metabolism was accompanied by aberrant proliferation and abrogation of apoptosis
      as determined by the extent of replicative DNA synthesis, S-phase fraction and
      Sub G0 (apoptotic) peak. Exposure of carcinogen-initiated cultures to 13C
      resulted in induction of C2-hydroxylation of E2 and of apoptosis and
      downregulation of hyperproliferation. Determination of altered cellular
      metabolism of E2 in response to initiators and modulators of carcinogenesis and
      evaluation of cell cycle related markers for proliferation and apoptosis may
      provide a mechanism-oriented approach to validate E2 metabolism as an endocrine
      biomarker for induction and prevention of human mammary carcinogenesis.

PMID- 9167996
TI  - Hormone-associated cancer: mechanistic similarities between human breast cancer
      and estrogen-induced kidney carcinogenesis in hamsters.
AB  - Estrogens are risk factors for human breast cancer and induce kidney tumors in
      Syrian hamsters. Mechanistic features of the estrogen-induced hamster kidney
      tumor model have been compared with corresponding aspects of human breast cancer
      to gain insight into the mechanism of human mammary oncogenesis. Shared
      characteristics point to a mechanism of metabolic activation of steroidal
      estrogens to 4-hydroxylated catechol metabolites that may undergo metabolic redox
      cycling, a mechanism of generation of reactive free radicals. Tumors may arise in
      cells genetically altered by various types of estrogen-induced DNA damage. At the
      same time, these altered cells may respond to estrogen receptor-mediated stimuli
      in support of cell transformation and growth.

PMID- 9167997
TI  - Medical hypothesis: bifunctional genetic-hormonal pathways to breast cancer.
AB  - As inherited germ line mutations, such as loss of BRCA1 or AT, account for less
      than 5% of all breast cancer, most cases involve acquired somatic perturbations.
      Cumulative lifetime exposure to bioavailable estradiol links most known risk
      factors (except radiation) for breast cancer. Based on a series of recent
      experimental and epidemiologic findings, we hypothesize that the multistep
      process of breast carcinogenesis results from exposure to endogenous or exogenous
      hormones, including phytoestrogens that directly or indirectly alter estrogen
      metabolism. Xenohormones are defined as xenobiotic materials that modify hormonal
      production; they can work bifunctionally, through genetic or hormonal paths,
      depending on the periods and extent of exposure. As for genetic paths,
      xenohormones can modify DNA structure or function. As for hormonal paths, two
      distinct mechanisms can influence the potential for aberrant cell growth:
      compounds can directly bind with endogenous hormone or growth factor receptors
      affecting cell proliferation or compounds can modify breast cell proliferation
      altering the formation of hormone metabolites that influence epithelial-stromal
      interaction and growth regulation. Beneficial xenohormones, such as indole-3
      carbinol, genistein, and other bioflavonoids, may reduce aberrant breast cell
      proliferation, and influence the rate of DNA repair or apoptosis and thereby
      influence the genetic or hormonal microenvironments. Upon validation with
      appropriate in vitro and in vivo studies, biologic markers of the risk for breast
      cancer, such as hormone metabolites, total bioavailable estradiol, and free
      radical generators can enhance cancer detection and prevention.

PMID- 9167999
TI  - Serum sex hormone levels are related to breast cancer risk in postmenopausal
      women.
AB  - We conducted a nested case-control study to prospectively evaluate the
      relationship of serum estrogens and androgens to risk of breast cancer in
      postmenopausal women. From 1977 to 1987, 3375 postmenopausal women free of cancer
      and not taking replacement estrogens donated blood to the Breast Cancer Serum
      Bank in Columbia, Missouri. Of these, 72 were subsequently diagnosed with breast
      cancer. For each case, two controls matched on age and date and time of day of
      blood collection were selected using incidence density matching. The median age
      of subjects at blood collection was 62 years; the time from blood collection to
      diagnosis ranged from less than 1 to 9.5 years with a median of 2.9 years. Risk
      of breast cancer was positively and significantly associated with serum levels of
      estrogens and androgens. Compared to women in the lowest quartile, those in the
      highest quartile for non-sex hormone-binding globulin (non-SHBG) bound
      (bioavailable) estradiol had a relative risk of 5.2 (95% confidence interval [CI]
      = 1.5-18.5) and those in the highest quartile for testosterone had a relative
      risk of 6.2 (95% CI = 2.0-19.0). Our results lend considerable support to the
      hypothesis that serum concentrations of estrogens and androgens are related to
      the subsequent diagnosis of breast cancer in postmenopausal women.

PMID- 9167998
TI  - During development, 17alpha-estradiol is a potent estrogen and carcinogen.
AB  - Neonatal administration of estradiol-17beta (E2-17beta) increases the nuclear DNA
      content in the mouse reproductive tract. Similar responses have been demonstrated
      for synthetic estrogens such as diethylstilbestrol. One of the questions raised
      regarding environmental estrogens such as organochlorines is whether they are
      potent enough to result in abnormal changes such as those demonstrated by both
      natural and synthetic estrogens. To test this hypothesis, female BALB/c mice were
      treated neonatally (days 1-5) with either E2-17beta or estradiol-17alpha (E2
      17alpha), an inactive stereoisomer in adult reproductive tissues. We also
      proposed whether neonatal administration of (E2-17alpha) was tumorigenic and
      whether the effects were age dependent. To answer these questions, one set each
      of 10 day-old treated and control mice received short-term secondary
      administration of E2-17beta, E2-17alpha, or cholesterol. Cervicovaginal tracts
      from intact BALB/c mice were examined histologically and by flow cytometry at 70
      days of age and by histology alone at 18 to 22 months of age. The results include
      several important findings: a) like E2-17beta, neonatal E2-17alpha treatment
      induced persistent vaginal cornification, hypospadias, vaginal concretions, and
      hyperproliferation in nearly 100% of the animals regardless of the secondary
      treatment for most groups; b) neonatal E2-17alpha treatment increased the nuclear
      DNA content of cervicovaginal epithelium at one-half both the level (mean DNA
      index of 1.02 vs 1.04) and incidence (22 vs 46% of the animals) of E2-17beta; c)
      short-term secondary treatment with E2-17alpha, unlike E2-17beta, did not
      significantly augment the increase in DNA content (13% for E2-17alpha vs 37 and
      56% for control and E2-17beta, respectively); and d) neonatal administration with
      E2-17alpha induced adenosquamous tumors in the reproductive tract in 25% of the
      animals. Therefore, the biological effects (estrogenic potency) of E2-17alpha may
      be age dependent.

PMID- 9168000
TI  - Endogenous estrogens and breast cancer risk: the case for prospective cohort
      studies.
AB  - It is generally agreed that estrogens, and possibly androgens, are important in
      the etiology of breast cancer, but no consensus exists as to the precise
      estrogenic or androgenic environment that characterizes risk, or the exogenous
      factors that influence the hormonal milieu. Nearly all the epidemiological
      studies conducted in the 1970s and 1980s were hospital-based case-control studies
      in which specimen sampling was performed well after the clinical appearance of
      the disease. Early prospective cohort studies also had limitations in their small
      sample sizes or short follow-up periods. However, more recent case-control
      studies nested within large cohorts, such as the New York University Women's
      Health Study and the Ormoni e Dieta nell'Eziologia dei Tumori study in Italy, are
      generating new data indicating that increased levels of estrone, estradiol and
      bioavailable estradiol, as well as their androgenic precursors, may be associated
      with a 4- to 6-fold increase in the risk of postmenopausal breast cancer. Further
      new evidence, which complements and expands the observations from the latter
      studies, shows that women with the thickest bone density, which may be a
      surrogate for cumulated exposure to hormones, experience severalfold increased
      risk of subsequent breast cancer as compared to women with thin bones. These data
      suggests that endogenous sex hormones are a key factor in the etiology of
      postmenopausal breast cancer. New prospective cohort studies should be conducted
      to examine the role of endogenous sex hormones in blood and urine samples
      obtained early in the natural history of breast cancer jointly with an assessment
      of bone density and of other important risk factors, such as mammographic
      density, physical activity, body weight, and markers of individual
      susceptibility, which may confer increased risk through an effect on the
      metabolism of endogenous hormones or through specific metabolic responses to
      Western lifestyle and diet.

PMID- 9168001
TI  - Sex steroid hormones, bone mineral density, and risk of breast cancer.
AB  - Increased bone mineral density (BMD), as a marker of higher integrated estrogen
      exposure over time, could be an important risk factor for postmenopausal breast
      cancer. In the Study of Osteoporotic Fractures 8065 non-black women age 65 years
      and older were followed for an average of 3.2 years. There were 121 incident
      breast cancer cases. The age adjusted incidence rate/1000 person years of breast
      cancer was substantially higher among women with high BMD at several measured
      bone sites. There was approximately a 2-fold higher risk of breast cancer for
      women in the upper as compared to the lower 25th percentile of BMD. Considerable
      controversy exists about the association of hormone replacement therapy (HRT) and
      increased risk of breast cancer. In this paper we modeled the effects of
      selection for HRT, presuming that women with lower BMD would be more likely to be
      on HRT, then estimated the observed versus potential risk of breast cancer among
      HRT users as compared to nonusers. The model suggests that the potential risk of
      breast cancer associated with HRT could be greatly underestimated and that
      postmenopausal women with high BMD who are placed on HRT could have a
      substantially increased risk of breast cancer. This model of increased risk of
      breast cancer associated with BMD and HRT needs to be evaluated within clinical
      trials and larger observational studies that include measures of BMD.

PMID- 9168002
TI  - A pilot study of urinary estrogen metabolites (16alpha-OHE1 and 2-OHE1) in
      postmenopausal women with and without breast cancer.
AB  - The two main pathways for metabolizing estrogen are via 16alpha-hydroxylation and
      2-hydroxylation. The 16alpha-hydroxy metabolites are biologically active; the 2
      hydroxy metabolites are not. It is suggested that women who metabolize a larger
      proportion of their endogenous estrogen via the 16alpha-hydroxy pathway may be at
      significantly elevated risk of breast cancer compared with women who metabolize
      proportionally more estrogen via the 2-hydroxy pathway. In particular, it is
      suggested that the ratio of urinary 2-hydroxyestrone (2-OHE1) to 16alpha
      hydroxyestrone (16alpha-OHE1) is an index of reduced breast cancer risk. This
      pilot study compared this ratio in postmenopausal women diagnosed with breast
      cancer to those of healthy controls. Urinary concentrations of estrone (E1),
      17beta-estradiol (E2) and estriol (E3) were also quantified. White women who were
      subjects in a previous breast cancer case-control study at our institution were
      eligible for inclusion. All participants provided a sample of their first morning
      urine. The results from the first 25 cases and 23 controls are presented here.
      The ratio of 2-OHE1 to 16alpha-OHE1 was 12% lower in the cases (p=0.58). However,
      urinary E1 was 30% higher (p=0.10), E2 was 58% higher (p=0.07), E3 was 15% higher
      (p=0.48), and the sum of E1, E2, and E3 was 22% higher (p=0.16) in the cases.
      These preliminary results do not support the hypothesis that the ratio of the two
      hydroxylation metabolites (2-OHE1/16alpha-OHE1) is an important risk factor for
      breast cancer or that it is a better predictor of breast cancer risk than levels
      of E1, E2 and E3 measured in urine.

PMID- 9168003
TI  - Quantifying estrogen metabolism: an evaluation of the reproducibility and
      validity of enzyme immunoassays for 2-hydroxyestrone and 16alpha-hydroxyestrone
      in urine.
AB  - Rapid and simple enzyme immunoassays (EIAs) were recently developed to measure 2
      hydroxyestrone and 16alpha-hydroxyestrone in unextracted urine. The balance
      between these competing estrogen metabolism pathways may serve as a biomarker of
      breast cancer risk. Before testing these assays in epidemiologic studies, we
      evaluated their reproducibility, and validity relative to gas chromatography-mass
      spectroscopy (GC-MS). Overnight 12-hr urine collections from five midfollicular
      premenopausal women, five midluteal premenopausal women, and five postmenopausal
      women were aliquoted and stored at -70 degrees C. Two aliquots from each woman
      were assayed with the EIAs in a random, blinded order, monthly over 4 months and
      1 year later. Reproducibility over 4 months was good for both metabolites in
      premenopausal women (coefficient of variation = 8-14%) and satisfactory in
      postmenopausal women (approximately 19%). Reproducibility over 12 months remained
      good in premenopausal women, but was poor in postmenopausal women, with mean
      readings increasing 50 to 100%. Wide variation in estrogen metabolite levels
      enabled a single EIA measurement to characterize individual differences among
      premenopausal women in midfollicular (intraclass correlation coefficient = 98
      99%) and midluteal phase (85-91%). A narrower range in metabolite levels among
      postmenopausal women reduced discrimination (78-82%). The correlation between EIA
      and GC-MS measurement was excellent for both metabolites (r>0.9), except for 2
      hydroxyestrone in postmenopausal women (r=0.6). Analysis of absolute agreement
      suggested that both EIAs were less sensitive than GC-MS, and each detected
      nonspecific background. The low concentration of estrogen metabolites in urine
      from postmenopausal women may explain the problems with reproducibility and
      validity in this menstrual group. Accordingly, more sensitive EIAs have been
      developed and are now being evaluated.

PMID- 9168004
TI  - In vitro synergistic interaction of alligator and human estrogen receptors with
      combinations of environmental chemicals.
AB  - The effect of mixtures of environmental chemicals with hormonal activity has not
      been well studied. To investigate this phenomenon, the estrogen receptor (ER)
      from the American alligator (aER) or human (hER) was incubated with [3H]17beta
      estradiol in the presence of selected environmental chemicals individually or in
      combination. The environmental chemicals included the insecticide chlordane,
      which has no estrogenic activity, and the pesticides dieldrin and toxaphene,
      which have very weak estrogenic activity. Chlordane, dieldrin, and toxaphene
      individually demonstrated no appreciable displacement of [3H]17beta-estradiol
      from aER and hER at the concentration tested. A combination of these chemicals
      inhibited the binding of [3H]17beta-estradiol by 20 to 40%. Alachlor, a chemical
      recently discovered to have weak estrogenic activity, also displaced [3H]17beta
      estradiol more effectively in combination with dieldrin than alone. These results
      indicate that combinations of some environmental chemicals inhibit [3H]17beta
      estradiol binding in a synergistic manner. This suggests that the ER may contain
      more than one site for binding environmental chemicals. The possibility that the
      ER binds multiple environmental chemicals adds another level of complexity to the
      interaction between the environment and the endocrine system.

PMID- 9168005
TI  - Neoplastic transformation of cultured mammalian cells by estrogens and
      estrogenlike chemicals.
AB  - Estrogens are clearly carcinogenic in humans and rodents but the mechanisms by
      which these hormones induce cancer are only partially understood. Stimulation of
      cell proliferation and gene expression by binding to the estrogen receptor is one
      important mechanism in hormonal carcinogenesis; however, estrogenicity is not
      sufficient to explain the carcinogenic activity of all estrogens because some
      estrogens are not carcinogenic. Estrogens are nonmutagenic in many assays but
      exhibit specific types of genotoxic activity under certain conditions. We have
      studied extensively the mechanisms by which estrogens induce neoplastic
      transformation in a model in vitro system and our findings are summarized in this
      review. 17beta-Estradiol (E2) and diethylstilbestrol (DES) and their metabolites
      induce morphological and neoplastic transformation of Syrian hamster embryo (SHE)
      cells that express no measurable levels of estrogen receptor. Treatment of the
      cells with E2 or DES fails to induce DNA damage, chromosome aberrations and gene
      mutations in SHE cells but results in numerical chromosome aberrations
      (aneuploidy) that could arise from microtubule disruption or disfunction of
      mitotic apparatus. Estrogen-induced genotoxicity is detected in cells following
      treatment with estrogen metabolites or following exogenous metabolic activation
      of estrogens. The estrogens induce DNA adduct formation that is detected by 32P
      postlabeling. Both aneuploidy induction and DNA damage caused by DNA adduct
      formation correlate with the estrogen-induced cell transformation and may be
      important in hormonal carcinogenesis. We propose that multiple effects of
      estrogens acting together cause genetic alterations leading to cell
      transformation.

PMID- 9168006
TI  - Estrogenic and DNA-damaging activity of Red No. 3 in human breast cancer cells.
AB  - Exposure to pesticides, dyes, and pollutants that mimic the growth promoting
      effects of estrogen may cause breast cancer. The pesticide DDT and the food
      colorant Red No. 3 were found to increase the growth of HTB 133 but not estrogen
      receptor (ER) negative human breast cells (HTB 125) or rat liver epithelial cells
      (RLE). Red No. 3, beta-estradiol, and DDT increase ER site-specific DNA binding
      to the estrogen response element in HTB 133 cells and increase cyclin-dependent
      kinase 2 activity in MCF-7 breast cancer cells. Site-specific DNA binding by p53
      in RLE, HTB 125, HTB 133, and MCF-7 cells was increased when they were treated
      with Red No. 3, which suggests that cellular DNA was damaged by this colorant.
      Red No. 3 increased binding of the ER from MCF-7 cells to the estrogen-responsive
      element. Consumption of Red No. 3, which has estrogenlike growth stimulatory
      properties and may be genotoxic, could be a significant risk factor in human
      breast carcinogenesis.

PMID- 9168007
TI  - Dietary estrogens stimulate human breast cells to enter the cell cycle.
AB  - It has been suggested that dietary estrogens neutralize the effect of synthetic
      chemicals that mimic the effects of estrogen (i.e., xenoestrogens, environmental
      estrogens). Genistein, a dietary estrogen, inhibits the growth of breast cancer
      cells at high doses but additional studies have suggested that at low doses,
      genistein stimulates proliferation of breast cancer cells. Therefore, if dietary
      estrogens are estrogenic at low doses, one would predict that they stimulate
      estrogen-receptor positive breast cancer cells to enter the cell cycle. Genistein
      and the fungal toxin zearalenone were found to increase the activity of cyclin
      dependent kinase 2 (Cdk2) and cyclin D1 synthesis and stimulate the
      hyperphosphorylation of the retinoblastoma susceptibility gene product pRb105 in
      MCF-7 cells. The steroidal antiestrogen ICI 182,780 suppressed dietary estrogen
      mediated activation of Cdk2. Dietary estrogens not only failed to suppress DDT
      induced Cdk2 activity, but were found to slightly increase enzyme activity. Both
      zearalenone and genistein were found to stimulate the expression of a luciferase
      reporter gene under the control of an estrogen response element in MVLN cells.
      Our findings are consistent with a conclusion that dietary estrogens at low
      concentrations do not act as antiestrogens, but act like DDT and estradiol to
      stimulate human breast cancer cells to enter the cell cycle.

PMID- 9168008
TI  - Estrogenic activity of natural and synthetic estrogens in human breast cancer
      cells in culture.
AB  - We investigated the estrogenic activity of various environmental pollutants
      (xenobiotics), in particular the xenoestrogen o,p-DDT, and compared their effects
      with those of endogenous estrogens, phytoestrogens, and mycoestrogens on estrogen
      receptor binding capacity, induction of estrogen end products, and activation of
      cell proliferation in estrogen-sensitive human breast cancer cells in monolayer
      culture. We also quantified the levels of phytoestrogens in extracts of some
      common foods, herbs, and spices and in human saliva following consumption of a
      high phytoestrogen food source (soy milk) to compare phytoestrogen abundance and
      bioavailability relative to the reported xenoestrogen burden in humans. Results
      show that natural endogenous estrogens, phytoestrogens, mycoestrogens, and
      xenoestrogens bind estrogen receptor (ER) in intact cells, but demonstrate marked
      differences in their ability to induce end products of estrogen action and to
      regulate cell proliferation. All of the different classes of estrogens stimulated
      cell proliferation at concentrations that half-saturated ER, but only some
      classes were able to induce estrogen-regulated end products. Genistein, a common
      phytoestrogen found in soy foods, differed from the xenoestrogen DDT in its
      effects on cell proliferation and ability to induce estrogen-regulated end
      products. Moreover, we found that many of the foods, herbs, and spices commonly
      consumed by humans contain significant amounts of phytoestrogens, and consumption
      of soy milk, a phytoestrogen-rich food, markedly increases the levels of
      phytoestrogens in saliva. In conclusion, our in vitro results predict that a diet
      high in phytoestrogens would significantly reduce the binding of weak
      xenoestrogens to ER in target tissues in vivo.

PMID- 9168009
TI  - Developing a marker of exposure to xenoestrogen mixtures in human serum.
AB  - It has been hypothesized that environmental estrogens may play a role in the
      increasing incidence of breast cancer, testicular cancer, and other problems of
      the reproductive system. While a single causal agent can be identified in cases
      in which humans have had occupational exposures, wildlife showing signs of
      reproductive damage have usually been exposed to a combination of endocrine
      disruptors that may act cumulatively. The development of appropriate biomarkers
      of cumulative exposure, and their measurement at developmental points where
      exposure is critical, are required to test the environmental estrogen hypothesis.
      Measuring levels of each of the xenoestrogens in blood is a better approximation
      of real exposure at the target organ level than inferring cumulative exposure by
      estimating from mass balance of dietary levels. However, the cumulative
      estrogenicity of mixtures cannot be directly concluded from individual
      xenoestrogen plasma levels. Two approaches may be used to assess total load: a)
      the development of methods to study mixtures of these xenoestrogens, to quantify
      their cumulative effects, and to begin to understand their interactions (i.e.,
      additivity, synergy, antagonism, or independent action), so that plasma
      concentrations may be translated into units of activity such as "estradiol
      equivalents"; and b) the development of methods to separate xenoestrogens from
      ovarian estrogens in blood and to directly measure the estrogenic activity of the
      xenoestrogen extract using a bioassay. The cumulative activity may be used as a
      marker of exposure to xenoestrogens. This article reports the development of a
      method to extract and separate xenoestrogens from ovarian estrogens using human
      serum as a source, followed by using a bioassay for determination of the
      cumulative xenoestrogen load as "estradiol equivalents."

PMID- 9168011
TI  - A dichotomy in the lipophilicity of natural estrogens, xenoestrogens, and
      phytoestrogens.
AB  - Using two independent analyses, it is demonstrated that natural (e.g., estradiol)
      and some xenoestrogens (e.g., methoxychlor metabolite) are characterized by a
      lipophilic region that is absent in nonestrogens as well as in phytoestrogens. It
      is suggested that this lipophilic region affects binding to specific receptors
      and may, in fact, differentiate harmful from beneficial estrogens.

PMID- 9168010
TI  - Predicting health effects of exposures to compounds with estrogenic activity:
      methodological issues.
AB  - Many substances are active in in vitro tests for estrogenic activity, but data
      from multigenerational and other toxicity studies are not available for many of
      those substances. Controversy has arisen, therefore, concerning the likelihood of
      adverse health effects. Based on a toxic equivalence factor risk assessment
      approach, some researchers have concluded that exposure to environmental
      estrogens is not associated with estrogen receptor (ER)-mediated health effects.
      Their rationale cites the low potency of these compounds in in vitro assays
      relative to estradiol, and the widespread exposure to pharmaceutical, endogenous,
      and dietary estrogens. This reasoning relies on two assumptions: that the
      relative estrogenic potency in in vitro assays is predictive of the relative
      potency for the most sensitive in vivo estrogenic effect; and that all estrogens
      act via the same mechanism to produce the most sensitive in vivo estrogenic
      effect. Experimental data reviewed here suggest that these assumptions may be
      inappropriate because diversity in both mechanism and effect exists for
      estrogenic compounds. Examples include variations in ER-ligand binding to
      estrogen response elements, time course of nuclear ER accumulation, patterns of
      gene activation, and other mechanistic characteristics that are not reflected in
      many in vitro assays, but may have significance for ER-mediated in vivo effects.
      In light of these data, this report identifies emerging methodological issues in
      risk assessment for estrogenic compounds: the need to address differences in in
      vivo end points of concern and the associated mechanisms; pharmacokinetics; the
      crucial role of timing and duration of exposure; interactions; and non-ER
      mediated activities of estrogenic compounds.

PMID- 9168012
TI  - Environmental effects and aquatic organisms: investigations of molecular
      mechanisms of carcinogenesis.
AB  - Cancers of the reproductive system are among the leading causes of mortality in
      women in the United States. While both genetic and environmental factors have
      been implicated in their etiology, the extent of the contribution of
      environmental factors to human diseases remains controversial. To better address
      the role of environmental exposures in cancer etiology, there has been an
      increasing focus on the development of nontraditional, environmentally relevant
      models. Our research involves the development of one such model. Gonadal tumors
      have been described in the softshell clam (Mya arenaria) in Maine and the
      hardshell clam (Mercenaria spp.) from Florida. Prevalence of these tumors is as
      high as 40% in some populations in eastern Maine and 60% in some areas along the
      Indian River in Florida. The average tumor prevalence in Maine and Florida is
      approximately 20 and 11%, respectively. An association has been suggested between
      the use of herbicides and the incidence of gonadal tumors in the softshell clam
      in Maine. The role of environmental exposures in the development of the tumors in
      Mercenaria in Florida is unknown; however, there is evidence that genetic factors
      may contribute to its etiology. Epidemiologic studies of human populations in
      these same areas show a higher than average mortality rate due to cancers of the
      reproductive system in women, including both ovarian and breast cancer. The
      relationship, if any, among these observations is unknown. Our studies on the
      molecular basis of this disease in clams may provide additional information on
      environmental exposures and their possible link to cancer in clams and other
      organisms, including humans.

PMID- 9168014
TI  - Breast cancer and pesticides in Hawaii: the need for further study.
AB  - Only 30% of all breast cancer can be explained by known risk factors. Increases
      in breast cancer incidence rates in Hawaii over the past few decades cannot be
      attributed solely to improvements in screening and detection. Avoidable
      environmental factors may contribute to a proportion of the unexplained cases.
      Emerging evidence on endocrine disruption suggests that environmental chemicals
      may play a role in the development of breast cancer. Agricultural chemicals,
      including endocrine disruptors, have been used intensively in Hawaii's island
      ecosystem over the past 40 years leaching into groundwater, and leading to
      unusually widespread occupational and general population exposures. This paper
      discusses breast cancer patterns in Hawaii in the context of documented episodes
      of exposure to two endocrine-disrupting chemicals, chlordane/heptachlor and 1,2
      dibromo-3-chloropropane (DBCP), at levels that sometimes exceeded federal
      standards by several orders of magnitude. In light of this history, detailed
      geographic-based studies should be undertaken in Hawaii to elucidate the
      potential role of environmental factors in the development of breast cancer and
      other diseases.

PMID- 9168013
TI  - Is there an association between exposure to environmental estrogens and breast
      cancer?
AB  - It was initially reported that levels of polychlorinated biphenyls (PCBs) or p,p'
      DDE were elevated in breast cancer patients (serum or tissue) versus controls.
      These results, coupled with reports that selected environmental estrogens
      decreased 17beta-estradiol (E2) 2-hydroxylase activity and increased the ratio of
      16alpha-hydroxyestrone/2-hydroxyestrone metabolites in MCF-7 human breast cancer
      cells, have led to the hypothesis that xenoestrogens are a preventable cause of
      breast cancer. More recent studies and analysis of organochlorine levels in
      breast cancer patients versus controls show that these contaminants are not
      elevated in the latter group. Moreover, occupational exposure to relatively high
      levels of PCBs and DDT/DDE are not associated with an increased incidence of
      breast cancer. A reexamination of the radiometric E2 2-hydroxylase assay in MCF-7
      cells with diverse estrogens, antiestrogens, and carcinogens showed that the
      mammary carcinogen benzo[a]pyrene induced this response and the antiestrogen ICI
      164,384 decreased E2 2-hydroxylase activity. Thus, E2 2-hydroxylase activity and
      the 16alpha-hydroxyestrone/2-hydroxyestrone metabolite ratio in MCF-7 cells does
      not predict xenoestrogens or mammary carcinogens.

PMID- 9168015
TI  - Mechanisms, proof, and unmet needs: the perspective of a cancer activist.
AB  - Cancer activists who participate with cancer researchers in shaping public health
      policy provide a different perspective on the question of breast cancer etiology.
      We place a higher priority on reducing women's exposure to suspected breast
      carcinogens than in debating the specific biochemical mechanisms by which these
      agents may operate. As the fruits of AIDS activism and antismoking campaigns
      illustrate, answers to mechanistic questions have not been and should not be the
      driving force behind public health policy. As such, cancer activists embrace a
      form of conservatism that advocates prudence in the face of exposure to
      estrogenic and other endocrine-disrupting chemicals. This perspective stands in
      contrast to scientific conservatism, which directs its caution toward the issue
      of proof. Unmet needs for cancer activists refer not so much to data gaps as to
      the failure to eliminate ongoing cancer hazards. For this author and activist,
      unmet needs include ending women's continued exposure to such common estrogenic
      compounds as detergents, triazine herbicides, plastics, and polychlorinated
      biphenyls.

PMID- 9168016
TI  - Effect of periodic box size on aqueous molecular dynamics simulation of a DNA
      dodecamer with particle-mesh Ewald method.
AB  - The particle-mesh Ewald (PME) method is considered to be both efficient and
      accurate for the evaluation of long-range electrostatic interactions in large
      macromolecular systems being studied by molecular dynamics simulations. This
      method assumes "infinite" periodic boundary conditions resembling the symmetry of
      a crystal environment. Can such a "solid-state" method accurately portray a
      macromolecular solute such as DNA in solution? To address this issue, we have
      performed three 1500-ps PME molecular dynamics (MD) simulations, each with a
      different box size, on the d(CGCGA6CG)-(CGT6CGCG) DNA dodecamer. The smallest box
      had the DNA solvated by a layer of water molecules of at least 5 A along each
      orthogonal direction. The intermediate size box and the largest box had the DNA
      solvated by a layer of water molecules of at least 10 A and 15 A, respectively,
      along each orthogonal direction. The intermediate size box in the present study
      is similar to the box size currently chosen by most workers in the field. Based
      on a comparison of RMSDs and curvature for this single DNA dodecamer sequence,
      the larger two box sizes do not appear to afford any extra benefit over the
      smallest box. The implications of this finding are briefly discussed.

PMID- 9168017
TI  - Three-dimensional image reconstruction of reconstituted smooth muscle thin
      filaments: effects of caldesmon.
AB  - Caldesmon inhibits actomyosin ATPase and filament sliding in vitro, and therefore
      may play a role in modulating smooth and non-muscle motile activities. A
      bacterially expressed caldesmon fragment, 606C, which consists of the C-terminal
      150 amino acids of the intact molecule, possesses the same inhibitory properties
      as full-length caldesmon and was used in our structural studies to examine
      caldesmon function. Three-dimensional image reconstruction was carried out from
      electron micrographs of negatively stained, reconstituted thin filaments
      consisting of actin and smooth muscle tropomyosin both with and without added
      606C. Helically arranged actin monomers and tropomyosin strands were observed in
      both cases. In the absence of 606C, tropomyosin adopted a position on the inner
      edge of the outer domain of actin monomers, with an apparent connection to sub
      domain 1 of actin. In 606C-containing filaments that inhibited acto-HMM ATPase
      activity, tropomyosin was found in a different position, in association with the
      inner domain of actin, away from the majority of strong myosin binding sites. The
      effect of caldesmon on tropomyosin position therefore differs from that of
      troponin on skeletal muscle filaments, implying that caldesmon and troponin act
      by different structural mechanisms.

PMID- 9168018
TI  - Multiphoton excitation fluorescence microscopy and spectroscopy of in vivo human
      skin.
AB  - Multiphoton excitation microscopy at 730 nm and 960 nm was used to image in vivo
      human skin autofluorescence from the surface to a depth of approximately 200
      microm. The emission spectra and fluorescence lifetime images were obtained at
      selected locations near the surface (0-50 microm) and at deeper depths (100-150
      microm) for both excitation wavelengths. Cell borders and cell nuclei were the
      prominent structures observed. The spectroscopic data suggest that reduced
      pyridine nucleotides, NAD(P)H, are the primary source of the skin
      autofluorescence at 730 nm excitation. With 960 nm excitation, a two-photon
      fluorescence emission at 520 nm indicates the presence of a variable, position
      dependent intensity component of flavoprotein. A second fluorescence emission
      component, which starts at 425 nm, is observed with 960-nm excitation. Such
      fluorescence emission at wavelengths less than half the excitation wavelength
      suggests an excitation process involving three or more photons. This conjecture
      is further confirmed by the observation of the super-quadratic dependence of the
      fluorescence intensity on the excitation power. Further work is required to
      spectroscopically identify these emitting species. This study demonstrates the
      use of multiphoton excitation microscopy for functional imaging of the metabolic
      states of in vivo human skin cells.

PMID- 9168019
TI  - Two-photon fluorescence microscopy of laurdan generalized polarization domains in
      model and natural membranes.
AB  - Two-photon excitation microscopy shows coexisting regions of different
      generalized polarization (GP) in phospholipid vesicles, in red blood cells, in a
      renal tubular cell line, and in purified renal brushborder and basolateral
      membranes labeled with the fluorescent probe laurdan. The GP function measures
      the relative water content of the membrane. In the present study we discuss
      images obtained with polarized laser excitation, which selects different
      molecular orientations of the lipid bilayer corresponding to different spatial
      regions. The GP distribution in the gel-phase vesicles is relatively narrow,
      whereas the GP distribution in the liquid-crystalline phase vesicles (DOPC and
      DLPC) is broad. Analysis of images obtained with polarized excitation of the
      liquid-crystalline phase vesicles leads to the conclusion that coexisting regions
      of different GP must have dimensions smaller than the microscope resolution
      (approximately 200 nm radially and 600 nm axially). Vesicles of an equimolar
      mixture of DOPC and DPPC show coexisting rigid and fluid domains (high GP and low
      GP), but the rigid domains, which are preferentially excited by polarized light,
      have GP values lower than the pure gel-phase domains. Cholesterol strongly
      modifies the domain morphology. In the presence of 30 mol% cholesterol, the broad
      GP distribution of the DOPC/DPPC equimolar sample becomes narrower. The sample is
      still very heterogeneous, as demonstrated by the separations of GP disjoined
      regions, which are the result of photoselection of regions of different lipid
      orientation. In intact red blood cells, microscopic regions of different GP can
      be resolved, whereas in the renal cells GP domains have dimensions smaller than
      the microscope resolution. Preparations of renal apical brush border membranes
      and basolateral membranes show well-resolved GP domains, which may result from a
      different local orientation, or the domains may reflect a real heterogeneity of
      these membranes.

PMID- 9168020
TI  - Analytical calculation of intracellular calcium wave characteristics.
AB  - We present a theoretical analysis of intracellular calcium waves propagated by
      calcium feedback at the inositol 1,4,5-trisphosphate (IP3) receptor. The model
      includes essential features of calcium excitability, but is still analytically
      tractable. Formulas are derived for the wave speed, amplitude, and width. The
      calculations take into account cytoplasmic Ca buffering, the punctate nature of
      the Ca release channels, channel inactivation, and Ca pumping. For relatively
      fast buffers, the wave speed is well approximated by V(infinity) =
      (J(eff)D(eff)/C0)1/2, where J(eff) is an effective, buffered source strength;
      D(eff) is the effective, buffered diffusion constant of Ca; and C(0) is the Ca
      threshold for channel activation. It is found that the saturability and finite on
      rate of buffers must be taken into account to accurately derive the wave speed
      and front width. The time scale governing Ca wave propagation is T(r), the time
      for Ca release to reach threshold to activate further release. Because IP3
      receptor inactivation is slow on this time scale, channel inactivation does not
      affect the wave speed. However, inactivation competes with Ca removal to limit
      wave height and front length, and for biological parameter ranges, it is
      inactivation that determines these parameters. Channel discreteness introduces
      only small corrections to wave speed relative to a model in which Ca is released
      uniformly from the surface of the stores. These calculations successfully predict
      experimental results from basic channel and cell parameters and explain the
      slowing of waves by exogenous buffers.

PMID- 9168021
TI  - Role of water on unfolding kinetics of helical peptides studied by molecular
      dynamics simulations.
AB  - Molecular dynamics simulations have been carried out with four polypeptides,
      Ala13, Val(13), Ser13, and Ala4Gly5Ala4, in vacuo and with explicit hydration.
      The unfolding of the polypeptides, which are initially fully alpha-helix in
      conformation, has been monitored during trajectories of 0.3 ns at 350 K. A rank
      of Ala < Val < Ser < Gly is found in the order of increasing rate of unwinding.
      The unfolding of Ala13 and Val(13) is completed in hundreds of picoseconds, while
      that of Ser13 is about one order of magnitude faster. The helix content of the
      peptide containing glycine residues falls to zero within a few picoseconds.
      Ramachandran plots indicate quite distinct equilibrium distributions and time
      evolution of dihedral angles in water and in vacuum for each residue type. The
      unfolding of polyalanine and polyvaline helices is accelerated due to solvation.
      In contrast, polyserine is more stable in water compared to vacuum, because its
      side chains can form intramolecular hydrogen bonds with the backbone more readily
      in vacuum, which disrupts the helix. Distribution functions of the spatial and
      angular position of water molecules in the proximity of the polypeptide backbone
      polar groups reveal the stabilization of the coiled structures by hydration. The
      transition from helix to coil is characterized by the appearance of a new peak in
      the probability distribution at a specific location characteristic of hydrogen
      bond formation between water and backbone polar groups. No significant insertion
      of water molecules is observed at the precise onset of unwinding, while (i, i+3)
      hydrogen bond formation is frequently detected at the initiation of alpha-helix
      unwinding.

PMID- 9168022
TI  - The extracellular potential of a myelinated nerve fiber in an unbounded medium
      and in nerve cuff models.
AB  - A model is presented for the calculation of single myelinated fiber action
      potentials in an unbounded homogeneous medium and in nerve cuff electrodes. The
      model consists of a fiber model, used to calculate the action currents at the
      nodes of Ranvier, and a cylindrically symmetrical volume conductor model in which
      the fiber's nodes are represented as point current sources. The extracellular
      action potentials were shown to remain unchanged if the fiber diameter and the
      volume conductor geometry are scaled by the same factor (principle of
      corresponding states), both in an unbounded homogeneous medium and in an
      inhomogeneous volume conductor. The influence of several cuff electrode
      parameters, among others, cuff length and cuff diameter, were studied, and the
      results were compared, where possible, with theoretical and experimental results
      as reported in the literature.

PMID- 9168023
TI  - Analysis of Fc(epsilon)RI-mediated mast cell stimulation by surface-carried
      antigens.
AB  - Clustering of the type I receptor for IgE (Fc[epsilon]RI) on mast cells initiates
      a cascade of biochemical processes that result in secretion of inflammatory
      mediators. To determine the Fc(epsilon)RI proximity, cluster size, and mobility
      requirements for initiating the Fc(epsilon)RI cascade, a novel experimental
      protocol has been developed in which mast cells are reacted with glass surfaces
      carrying different densities of both antigen and bound IgE, and the cell's
      secretory response to these stimuli is measured. The results have been analyzed
      in terms of a model based on the following assumptions: 1) the glass surface
      antigen distribution and consequently that of the bound IgE are random; 2)
      Fc(epsilon)RI binding to these surface-bound IgEs immobilizes the former and
      saturates the latter; 3) the cell surface is formally divided into small
      elements, which function as a secretory stimulus unit when occupied by two or
      more immobilized IgE-Fc(epsilon)RI complexes; 4) alternatively, similar
      stimulatory units can be formed by binding of surface-carried IgE dimers to two
      Fc(epsilon)RI. This model yielded a satisfactory and self-consistent fitting of
      all of the different experimental data sets. Hence the present results establish
      the essential role of Fc(epsilon)RI immobilization for initiating its signaling
      cascade. Moreover, it provides independent support for the notion that as few as
      two Fc(epsilon)RIs immobilized at van der Waals contact constitute an "elementary
      stimulatory unit" leading to mast cell (RBL-2H3 line) secretory response.

PMID- 9168024
TI  - Shaker pore structure as predicted by annealed atomic simulation using symmetry
      and novel geometric restraints.
AB  - Recent studies making use of channel-blocking peptides as molecular calipers have
      revealed the architecture of the pore-forming region of Shaker-type potassium
      channels. Here we show that the low-resolution, experimentally derived geometric
      information can be incorporated as restraints within the context of an annealed
      molecular dynamics simulation to predict an atomic structure for the channel pore
      which, by virtue of restraints, conforms to the experimental evidence. The
      simulation is reminiscent of the computational method employed by nuclear
      magnetic resonance (NMR) spectroscopists to resolve solution structures of
      biological macromolecules, but in lieu of restraints conventionally derived from
      NMR spectra, novel restraints are developed that include side-chain orientation
      of amino acid residues and assumed symmetry of protein subunits. The method
      presented here offers the possibility of expanding cooperation between simulation
      and experiment in developing structural models, especially for systems such as
      ion channels whose three-dimensional structures may not be amenable to
      determination by direct methods at the present time.

PMID- 9168025
TI  - Helix bending in alamethicin: molecular dynamics simulations and amide hydrogen
      exchange in methanol.
AB  - Molecular dynamics simulations of alamethicin in methanol were carried out with
      either a regular alpha-helical conformation or the x-ray crystal structure as
      starting structures. The structures rapidly converged to a well-defined hydrogen
      bonding pattern with mixed alpha-helical and 3(10)-helical hydrogen bonds,
      consistent with NMR structural characterization, and did not unfold throughout
      the 1-ns simulation, despite some sizable backbone fluctuations involving
      reversible breaking of helical hydrogen bonds. Bending of the helical structure
      around residues Aib10-Aib13 was associated with reversible flips of the peptide
      bonds involving G11 (Aib10-G11 or G11-L12 peptide bonds), yielding discrete
      structural states in which the Aib10 carbonyl or (rarely) the G11 carbonyl was
      oriented away from the peptide helix. These peptide bond reversals could be
      accommodated without greatly perturbing the adjacent helical structure, and
      intramolecular hydrogen bonding was generally maintained in bent states through
      the formation of new (non-alpha or 3[10]) hydrogen bonds with good geometries:
      G11 NH-V9 CO (inverse gamma turn), Aib13 NH-Aib8 CO (pi-helix) and, rarely, L12
      NH- Q7 NH (pi-helix). These observations may reconcile potentially conflicting
      NMR structural information for alamethicin in methanol, in which evidence for
      conformational flexibility in the peptide sequence before P14 (G11-Aib13)
      contrasts with the stability of backbone amide NH groups to exchange with
      solvent. Similar reversible reorientation of the Thr11-Gly12 peptide bond of
      melittin is also observed in dynamics simulations in methanol (R. B. Sessions, N.
      Gibbs, and C. E. Dempsey, submitted). This phenomenon may have some role in the
      orientation of the peptide carbonyl in solvating the channel lumen in membrane
      ion channel states of these peptides.

PMID- 9168026
TI  - Fluctuation-driven directional flow in biochemical cycle: further study of
      electric activation of Na,K pumps.
AB  - Directional flow of information and energies is characteristic of many types of
      biochemical reactions, for instance, ion transport, energy coupling during ATP
      synthesis, and muscle contraction. Can a fluctuating force field, or a noise,
      induce such a directional flux? Previous work has shown that Na,K-ATPase of human
      erythrocyte can absorb free energy from an externally applied random-telegraph
      noise (RTN) electric field to pump Rb+ up its concentration gradient. However,
      the RTN field used in these experiments was constant in amplitude and would not
      mimic fluctuating electric fields of a cell membrane. Here we show that electric
      fields which fluctuate both in life time and in amplitude, and thus, better
      mimicking the transmembrane electric fields of a cell, can also induce Rb+
      pumping by Na,K-ATPase. A Gaussian-RTN-electric field, or a field with amplitude
      fluctuating according to the Gaussian distribution, with varied standard
      deviation (sigma), induced active pumping of Rb+ in human erythrocyte, which was
      completely inhibited by ouabain. Increased values for sigma led to a nonmonotonic
      reduction in pumping efficiency. A general formula for calculating the ion
      transport in a biochemical cycle induced by fluctuating electric field has been
      derived and applied to a simple four-state electroconformational coupling (ECC)
      model. It was found that the calculated efficiency in the energy coupling
      decreased with increasing sigma value, and this effect was relatively small and
      monotonic, whereas experimental data were more complex: monotonic under certain
      sets of conditions but nonmonotonic under different sets. The agreement in
      general features but disagreement in some fine features suggest that there are
      other properties of the electric activation process for Na,K-ATPase that cannot
      be adequately described by the simple ECC model, and further refinement of the
      ECC model is required.

PMID- 9168027
TI  - Time-resolved charge translocation by the Ca-ATPase from sarcoplasmic reticulum
      after an ATP concentration jump.
AB  - Time-resolved measurements of currents generated by Ca-ATPase from fragmented
      sarcoplasmic reticulum (SR) are described. SR vesicles spontaneously adsorb to a
      black lipid membrane acting as a capacitive electrode. Charge translocation by
      the enzyme is initiated by an ATP concentration jump performed by the light
      induced conversion of an inactive precursor (caged ATP) to ATP with a time
      constant of 2.0 ms at pH 6.2 and 24 degrees C. The shape of the current signal is
      triphasic, an initial current flow into the vesicle lumen is followed by an
      outward current and a second slow inward current. The time course of the current
      signal can be described by five relaxation rate constants, lambda1 to lambda5
      plus a fixed delay D approximately 1-3 ms. The electrical signal shows that 1)
      the reaction cycle of the Ca-ATPase contains two electrogenic steps; 2) positive
      charge is moved toward the luminal side in the first rapid step and toward the
      cytoplasmic side in the second slow step; 3) at least one electroneutral reaction
      precedes the electrogenic steps. Relaxation rate constant lambda3 reflects ATP
      binding, with lambda(3,max) approximately 100 s(-1). This step is electroneutral.
      Comparison with the kinetics of the reaction cycle shows that the first
      electrogenic step (inward current) occurs before the decay of E2P. Candidates are
      the formation of phosphoenzyme from E1ATP (lambda2 approximately 200 s[-1]) and
      the E1P --> E2P transition (D approximately 1 ms or lambda1 approximately 300 s[
      1]). The second electrogenic transition (outward current) follows the formation
      of E2P (lambda4 approximately 3 s[-1]) and is tentatively assigned to H+
      countertransport after the dissociation of Ca2+. Quenched flow experiments
      performed under the conditions of the electrical measurements 1) demonstrate
      competition by caged ATP for ATP-dependent phosphoenzyme formation and 2) yield a
      rate constant for phosphoenzyme formation of 200 s(-1). These results indicate
      that ATP and caged ATP compete for the substrate binding site, as suggested by
      the ATP dependence of lambda3 and favor correlation of lambda2 with phosphoenzyme
      formation.

PMID- 9168028
TI  - Role of S4 segments and the leucine heptad motif in the activation of an L-type
      calcium channel.
AB  - Basic residues in the S4 segments of voltage-dependent channels and leucines
      within the heptad repeat motif in the S4-S5 region of Shaker potassium channels
      have been shown to have important influences on activation. Here we have compared
      the relative importance for activation of S4 arginines (mutated to neutral or
      negative residues) in each of the four repeats of a chimeric L-type calcium
      channel. Significant effects on midpoint potential and time constant of
      activation were produced by mutations in repeats I and III but not in repeats II
      and IV. Leucine or isoleucine mutations in repeats I and III had the same effect
      on the voltage dependence of calcium channel activation as the mutations at
      equivalent positions in the Shaker channel, indicating that the heptad motif
      plays a fundamental role in channel activation.

PMID- 9168029
TI  - Two-dimensional components and hidden dependencies provide insight into ion
      channel gating mechanisms.
AB  - Correlations between the durations of adjacent open and shut intervals recorded
      from ion channels contain information about the underlying gating mechanism. This
      study presents an additional approach to extracting the correlation information.
      Detailed correlation information is obtained directly from single-channel data
      and quantified in a manner that can provide insight into the connections among
      the states underlying the gating. The information is obtained independently of
      any specific kinetic scheme, except for the general assumption of Markov gating.
      The durations of adjacent open and shut intervals are binned into two-dimensional
      (2-D) dwell-time distributions. The 2-D (joint) distributions are fitted with
      sums of 2-D exponential components to determine the number of 2-D components,
      their volumes, and their open and closed time constants. The dependency of each 2
      D component is calculated by comparing its observed volume to the volume that
      would be expected if open and shut intervals paired independently. The estimated
      component dependencies are then used to suggest gating mechanisms and to provide
      a powerful means of examining whether proposed gating mechanisms have the correct
      connections among states. The sensitivity of the 2-D method can identify hidden
      components and dependencies that can go undetected by previous correlation
      methods.

PMID- 9168030
TI  - How to make tubular crystals by reconstitution of detergent-solubilized Ca2(+)
      ATPase.
AB  - In an attempt to better define the parameters governing reconstitution and two
      dimensional crystallization of membrane proteins, we have studied Ca2(+)-ATPase
      from rabbit sarcoplasmic reticulum. This ion pump forms vanadate-induced crystals
      in its native membrane and has previously been reconstituted at high lipid-to
      protein ratios for functional studies. We have characterized the reconstitution
      of purified Ca2(+)-ATPase at low lipid-to-protein ratios and discovered
      procedures that produce long, tubular crystals suitable for helical
      reconstruction. C12E8 (n-dodecyl-octaethylene-glycol monoether) was used to fully
      solubilize various mixtures of lipid and purified Ca2(+)-ATPase, and BioBeads
      were then used to remove the C12E8. Slow removal resulted in two populations of
      vesicles, and the proteoliposome population was separated from the liposome
      population on a sucrose density gradient. These proteoliposomes had a lipid-to
      protein ratio of 1:2, and virtually 100% of molecules faced the outside of
      vesicles, as determined by fluorescein isothiocyanate labeling. Cycles of freeze
      thaw caused considerable aggregation of these proteoliposomes, and, if
      phosphatidyl ethanolamine and phosphatidic acid were included, or if the bilayers
      were doped with small amounts of C12E8, vanadate-induced tubular crystals grew
      from the aggregates. Thus our procedure comprised two steps-reconstitution
      followed by crystallization-allowing us to consider mechanisms of bilayer
      formation separately from those of crystallization and tube formation.

PMID- 9168031
TI  - N-acylphosphatidylethanolamines: effect of the N-acyl chain length on its
      orientation.
AB  - N-Acylphosphatidylethanolamines, or NAPEs, are found in tissues involved in
      degenerating processes, such as dehydrated endosperm of seeds, erythrocyte
      membranes, or cell injury. To determine the conformation and orientation of the
      acyl chains of these phospholipids, NAPEs with deuterated N-acyl chains of 6 and
      16 carbon atoms were synthesized and studied by transmission and attenuated total
      reflectance (ATR) infrared spectroscopy. For N-C16d-DPPE, the ATR measurements
      show that the N-acyl chain has the same orientation as the two acyl chains
      attached to the glycerol moiety, while the N-acyl chain of N-C6d-DPPE is randomly
      oriented. These results demonstrate that for N-C16d-DPPE, the N-acyl chain is
      embedded into the hydrophobic core of the bilayer, while for the short chain
      derivative the N-acyl chain remains in the lipid headgroup region. The analysis
      of the carbonyl stretching band and of the amide I band suggests that, for the
      long N-acyl chain lipid, the ester C=O and the N-H groups are linked by
      intermolecular hydrogen bonds.

PMID- 9168032
TI  - Cholesterol in condensed and fluid phosphatidylcholine monolayers studied by
      epifluorescence microscopy.
AB  - Epifluorescence microscopy was used to investigate the effect of cholesterol on
      monolayers of dipalmitoylphosphatidylcholine (DPPC) and 1 -palmitoyl-2-oleoyl
      phosphatidylcholine (POPC) at 21 +/- 2 degrees C using 1 mol% 1-palmitoyl-2-[12
      [(7-nitro-2-1, 3-benzoxadizole-4-yl)amino]dodecanoyl]phosphatidylcholine (NBD-PC)
      as a fluorophore. Up to 30 mol% cholesterol in DPPC monolayers decreased the
      amounts of probe-excluded liquid-condensed (LC) phase at all surface pressures
      (pi), but did not effect the monolayers of POPC, which remained in the liquid
      expanded (LE) phase at all pi. At low pi (2-5 mN/m), 10 mol% or more cholesterol
      in DPPC induced a lateral phase separation into dark probe-excluded and light
      probe-rich regions. In POPC monolayers, phase separation was observed at low pi
      when > or =40 mol% or more cholesterol was present. The lateral phase separation
      observed with increased cholesterol concentrations in these lipid monolayers may
      be a result of the segregation of cholesterol-rich domains in ordered fluid
      phases that preferentially exclude the fluorescent probe. With increasing pi,
      monolayers could be transformed from a heterogeneous dark and light appearance
      into a homogeneous fluorescent phase, in a manner that was dependent on pi and
      cholesterol content. The packing density of the acyl chains may be a determinant
      in the interaction of cholesterol with phosphatidylcholine (PC), because the
      transformations in monolayer surface texture were observed in phospholipid
      (PL)/sterol mixtures having similar molecular areas. At high pi (41 mN/m),
      elongated crystal-like structures were observed in monolayers containing 80-100
      mol% cholesterol, and these structures grew in size when the monolayers were
      compressed after collapse. This observation could be associated with the
      segregation and crystallization of cholesterol after monolayer collapse.

PMID- 9168033
TI  - The action of local anesthetics on myelin structure and nerve conduction in toad
      sciatic nerve.
AB  - X-ray scattering and electrophysiological experiments were performed on toad
      sciatic nerves in the presence of local anesthetics. In vitro experiments were
      performed on dissected nerves superfused with Ringer's solutions containing
      procaine, lidocaine, tetracaine, or dibucaine. In vivo experiments were performed
      on nerves dissected from animals anesthesized by targeted injections of
      tetracaine-containing solutions. In all cases the anesthetics were found to have
      the same effects on the x-ray scattering spectra: the intensity ratio of the even
      order to the odd-order reflections increases and the lattice parameter increases.
      These changes are reversible upon removal of the anesthetic. The magnitude of the
      structural changes varies with the duration of the superfusion and with the
      nature and concentration of the anesthetic molecule. A striking quantitative
      correlation was observed between the structural effects and the potency of the
      anesthetic. Electron density profiles, which hardly showed any structural
      alteration of the unit membrane, clearly indicated that the anesthetics have the
      effect of moving the pairs of membranes apart by increasing the thickness of the
      cytoplasmic space. Electrophysiological measurements performed on the very
      samples used in the x-ray scattering experiments showed that the amplitude of the
      compound action potential is affected earlier than the structure of myelin (as
      revealed by the x-ray scattering experiments), whereas conduction velocity
      closely follows the structural alterations.

PMID- 9168034
TI  - Packing constraints and electrostatic surface potentials determine transmembrane
      asymmetry of phosphatidylethanol.
AB  - The energetic determinants of the distribution of anionic phospholipids across a
      phosphatidylcholine (PtdCho) bilayer with different packing constraints in the
      two leaflets were studied, using (13)CH2-ethyl-labeled phosphatidylethanol
      (PtdEth) as a (13)C NMR membrane probe. PtdEth is unique in exhibiting a split
      (13)CH2-ethyl resonance in sonicated vesicles, the two components originating
      from the inner and outer leaflets, thus permitting the determination of the
      PtdEth concentration in each leaflet. Small and large unilamellar PtdEth-PtdCho
      vesicles were prepared in solutions of different ionic strengths. A quantitative
      expression for the transbilayer distribution of PtdEth, based on the balance
      between steric and electrostatic factors, was derived. The transbilayer
      difference in packing constraints was obtained from the magnitude of the PtdEth
      signal splitting. The electrostatic contribution could be satisfactorily
      described by the transmembrane difference in Gouy-Chapman surface potentials. At
      low (0.1-0.25%) PtdEth levels and high (up to 500 mM) salt concentrations, PtdEth
      had a marked fivefold preference for the inner leaflet, presumably because of its
      small headgroup, which favors tighter packing. At higher PtdEth content (4.8
      9.1%) and low salt concentrations, where electrostatic repulsion becomes a
      dominant factor, the asymmetry was markedly reduced and an almost even
      distribution across the bilayer was obtained. In less curved, large vesicles,
      where packing constraints in the two leaflets are approximately the same, the
      PtdEth distribution was almost symmetrical. This study is the first quantitative
      analysis of the balance between steric and electrostatic factors that determines
      the equilibrium transbilayer distribution of charged membrane constituents.

PMID- 9168035
TI  - Interaction of dystrophin fragments with model membranes.
AB  - The interaction with membrane lipids of recombinant fragments of human
      dystrophin, corresponding to a single structural repeating unit of the rod
      domain, was examined. Surface plasmon resonance, constant-pressure isotherms in a
      Langmuir surface film balance, and interfacial rheology were used to observe
      binding of the polypeptides and its effects on the properties of the lipid film.
      Modification of the monolayer properties was found to depend on the presence of
      phosphatidylserine in the lipid mixture and on the native tertiary fold of the
      polypeptide; thus a fragment with the minimum chain length required for folding
      (117 residues) or longer caused a contraction of the surface area at constant
      pressure, whereas fragments of 116 residues or less had no effect. The full
      extent of contraction was reached at a surface concentration of lipid
      corresponding to an average area of about 42 A2 per lipid molecule. A dystrophin
      fragment with the native, folded conformation induced a large increase in surface
      shear viscosity of the lipid film, whereas an unfolded fragment had no effect.
      Within a wide range of applied shear, the shear viscosity remained Newtonian.
      Binding of liposomes to immobilized dystrophin fragments could be observed by
      surface plasmon resonance and was again related to the conformational state of
      the polypeptide and the presence of phosphatidylserine in the liposomes. Our
      results render it likely that intact dystrophin interacts directly and strongly
      with the sarcolemmal lipid bilayer and grossly modifies its material properties.

PMID- 9168036
TI  - Adsorption of bovine prothrombin to spread phospholipid monolayers.
AB  - The interaction of bovine prothrombin with phospholipids was measured, using as
      the lipid source monolayers spread at the air-buffer interface. Fluorescence
      spectroscopy was implemented to determine the equilibrium concentration of free
      prothrombin in the aqueous subphase of the protein-monolayer suspensions, in a
      continuous assay system. The increase in surface pressure (pi) from the protein
      monolayer adsorption was also measured and, with values of the adsorbed protein
      concentration (c[s]), was used to calculate dc(s)/d(pi). At a particular
      phosphatidylserine (PS) content of liquid-expanded (LE) phosphatidylcholine
      (PC)/PS monolayers, dc(s)/d(pi) was independent of the initial surface pressure
      (pi[i]), when this latter value exceeded 30 mN/m. However, dc(s)/d(pi) varied
      significantly with the relative PS content of the monolayer. Values of the
      equilibrium dissociation constants calculated from the concentration dependence
      of delta(pi) indicated that the affinity of prothrombin for LE monolayers was
      higher at higher PS contents and lower packing densities. The affinity of
      prothrombin for liquid-condensed (LC) PC/PS monolayers was found to be much
      weaker relative to LE monolayers of similar phospholipid composition. This
      approach, employing spread monolayers to study prothrombin-phospholipid binding,
      coupled with a simple and accurate method to determine the free protein
      concentration in protein-monolayer suspensions, offers significant advantages for
      the investigation of protein-membrane interaction. The equilibrium
      characteristics that describe the interaction of prothrombin with the different
      phospholipid monolayers under various conditions also provide support for
      previous results which indicated that hydrophobic interactions are involved in
      the adsorption of vitamin K-dependent coagulation and anticoagulation proteins to
      model membrane systems.

PMID- 9168037
TI  - Bending elasticities of model membranes: influences of temperature and sterol
      content.
AB  - Giant liposomes obtained by electroformation and observed by phase-contrast video
      microscopy show spontaneous deformations originating from Brownian motion that
      are characterized, in the case of quasispherical vesicles, by two parameters
      only, the membrane tension sigma and the bending elasticity k(c). For liposomes
      containing dimyristoyl phosphatidylcholine (DMPC) or a 10 mol% cholesterol/DMPC
      mixture, the mechanical property of the membrane, k(c), is shown to be
      temperature dependent on approaching the main (thermotropic) phase transition
      temperature T(m). In the case of DMPC/cholesterol bilayers, we also obtained
      evidence for a relation between the bending elasticity and the corresponding
      temperature/cholesterol molecular ratio phase diagram. Comparison of
      DMPC/cholesterol with DMPC/cholesterol sulfate bilayers at 30 degrees C
      containing 30% sterol ratio shows that k(c) is independent of the surface charge
      density of the bilayer. Finally, bending elasticities of red blood cell (RBC)
      total lipid extracts lead to a very low k(c) at 37 degrees C if we refer to
      DMPC/cholesterol bilayers. At 25 degrees C, the very low bending elasticity of a
      cholesterol-free RBC lipid extract seems to be related to a phase coexistence, as
      it can be observed by solid-state (31)P-NMR. At the same temperature, the
      cholesterol-containing RBC lipid extract membrane shows an increase in the
      bending constant comparable to the one observed for a high cholesterol ratio in
      DMPC membranes.

PMID- 9168038
TI  - Morphological changes induced by phospholipase C and by sphingomyelinase on large
      unilamellar vesicles: a cryo-transmission electron microscopy study of liposome
      fusion.
AB  - Cryo-transmission electron microscopy has been applied to the study of the
      changes induced by phospholipase C on large unilamellar vesicles containing
      phosphatidylcholine, as well as to the action of sphingomyelinase on vesicles
      containing sphingomyelin. In both cases vesicle aggregation occurs as the
      earliest detectable phenomenon; later, each system behaves differently.
      Phospholipase C induces vesicle fusion through an intermediate consisting of
      aggregated and closely packed vesicles (the "honeycomb structure") that finally
      transforms into large spherical vesicles. The same honeycomb structure is also
      observed in the absence of enzyme when diacylglycerols are mixed with the other
      lipids in organic solution, before hydration. In this case the sample then
      evolves toward a cubic phase. The fact that the same honeycomb intermediate can
      lead to vesicle fusion (with enzyme-generated diacylglycerol) or to a cubic phase
      (when diacylglycerol is premixed with the lipids) is taken in support of the
      hypothesis according to which a highly curved lipid structure ("stalk") would act
      as a structural intermediate in membrane fusion. Sphingomyelinase produces
      complete leakage of vesicle aqueous contents and an increase in size of about one
      third of the vesicles. A mechanism of vesicle opening and reassembling is
      proposed in this case.

PMID- 9168039
TI  - Combinations of fluorescently labeled pulmonary surfactant proteins SP-B and SP-C
      in phospholipid films.
AB  - Hydrophobic pulmonary surfactant (PS) proteins B (SP-B) and C (SP-C) modulate the
      surface properties of PS lipids. Epifluorescence microscopy was performed on
      solvent-spread monolayers of fluorescently labeled porcine SP-B (R-SP-B, labeled
      with Texas Red) and SP-C (F-SP-C, labeled with fluorescein) in
      dipalmitoylphosphatidylcholine (DPPC) (at protein concentrations of 10 and 20
      wt%, and 10 wt% of both) under conditions of cyclic compression and expansion.
      Matrix-assisted laser desorption/ionization (MALDI) spectroscopy of R-SP-B and F
      SP-C indicated that the proteins were intact and labeled with the appropriate
      fluorescent probe. The monolayers were compressed and expanded for four cycles at
      an initial rate of 0.64 A2 x mol(-1) x s(-1) (333 mm2 x s x [-1]) up to a surface
      pressure pi approximately 65 mN/m, and pi-area per residue (pi-A) isotherms at 22
      +/- 1 degrees C were obtained. The monolayers were microscopically observed for
      the fluorescence emission of the individual proteins present in the film lipid
      matrix, and their visual features were video recorded for image analysis. The pi
      A isotherms of the DPPC/protein monolayers showed characteristic "squeeze out"
      effects at pi approximately 43 mN/m for R-SP-B and 55 mN/m for F-SP-C, as had
      previously been observed for monolayers of the native proteins in DPPC. Both
      proteins associated with the expanded (fluid) phase of DPPC monolayers remained
      in or associated with the monolayers at high pi (approximately 65 mN/m) and
      redispersed in the monolayer upon its reexpansion. At comparable pi and
      area/molecule of the lipid, the proteins reduced the amounts of condensed (gel
      like) phase of DPPC monolayers, with F-SP-C having a greater effect on a weight
      basis than did R-SP-B. In any one of the lipid/protein monolayers the amounts of
      the DPPC in condensed phase were the same at equivalent pi during compression and
      expansion and from cycle to cycle. This indicated that only minor loss of
      components from these systems occurred between compression-expansion cycles. This
      study indicates that hydrophobic PS proteins associate with the fluid phase of
      DPPC in films, some proteins remain at high surface pressures in the films, and
      such lipid-protein films can still attain high pi during compression.

PMID- 9168040
TI  - Order in phospholipid Langmuir-Blodgett monolayers determined by total internal
      reflection fluorescence.
AB  - Orientational order parameters of two diphenylhexatriene (DPH)-based fluorescent
      probes, 2-(3-(diphenylhexatrienyl)propanoyl)-1-hexadecanoyl-sn-glycero-3-p
      hosphocholine (DPHpPC) and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5
      hexatriene (TMA-DPH), in dipalmitoylphosphatidylcholine (DPPC) Langmuir-Blodgett
      monolayers on quartz have been determined by total internal reflection
      fluorescence (TIRF). From these order parameters orientation distributions were
      reconstructed by the maximum-entropy method. For monolayers transferred from the
      liquid-condensed phase, preferential tilt angles with respect to the substrate
      normal around 14 degrees in the tail region and 5 degrees near the glycerol-acyl
      chain linkage were found, as reflected by the DPHpPC and TMA-DPH probes,
      respectively. The degree of ordering near the headgroup region seems to be larger
      than that further away from the surface. A substantial fraction of the TMA-DPH
      probes have a flat orientation and are probably located between the phospholipid
      headgroups and the substrate surface. Monolayers transferred from the liquid
      expanded phase show a more random ordering, and most of the probe molecules
      (DPHpPC) are more or less flat on the surface. The results are consistent with
      earlier atomic force microscopy measurements on identical monolayers and are in
      reasonable agreement with previously published data on other organized
      phospholipid systems.

PMID- 9168041
TI  - Fluorescence quenching and electron spin resonance study of percolation in a two
      phase lipid bilayer containing bacteriorhodopsin.
AB  - The effect of bacteriorhodopsin (BR) on the percolation properties of
      dimyristoylphosphatidylcholine/distearoylphosphatidylcholine bilayers was
      examined by studying the quenching of a lipid-bound fluorophore by a lipid-bound
      quencher, and by spin-spin interactions of a nitroxide-labeled lipid using
      electron spin resonance (ESR). At the low concentrations of BR used, differential
      scanning calorimetry showed that although the transition enthalpy was reduced in
      a concentration-dependent manner by incorporation of BR, the solidus and fluidus
      phase boundaries and overall shape of the heat capacity profiles were essentially
      unchanged. However, fluorescence quenching and spin-label ESR data showed that
      the domain topology, as reflected in the percolation properties, is strongly
      affected by the protein. In contrast to our previous fluorescence data for the
      pure lipid mixtures, quenching in the coexistence region is independent of the
      fluid phase fraction when BR is present. In addition, the percolation threshold
      estimated by spin-label ESR is shifted in the presence of BR to a higher gel
      phase fraction at a given lipid composition. Both the fluorescence quenching and
      spin-label ESR data, together with the results of earlier simulations, strongly
      suggest that the fluid phase domains are substantially larger and/or less
      ramified in the presence of BR than in its absence. We have previously reported a
      similar effect of a transmembrane peptide, pOmpA (Escherichia coli outer membrane
      protein A signal peptide), on fluid domain connectivity in binary
      phosphatidylcholine mixtures.

PMID- 9168042
TI  - Energy of dissociation of lipid bilayer from the membrane skeleton of red blood
      cells.
AB  - The association between the lipid bilayer and the membrane skeleton is important
      to cell function. In red blood cells, defects in this association can lead to
      various forms of hemolytic anemia. Although proteins involved in this association
      have been well characterized biochemically, the physical strength of this
      association is only beginning to be studied. Formation of a small cylindrical
      strand of membrane material (tether) from the membrane involves separation of the
      lipid bilayer from the membrane skeleton. By measuring the force required to form
      a tether, and knowing the contribution to the force due to the deformation of a
      lipid bilayer, it is possible to calculate the additional contribution to the
      work of tether formation due to the separation of membrane skeleton from the
      lipid bilayer. In the present study, we measured the tethering force during
      tether formation using a microcantilever (a thin, flexible glass fiber) as a
      force transducer. Numerical calculations of the red cell contour were performed
      to examine how the shape of the contour affects the calculation of tether radius,
      and subsequently separation work per unit area W(sk) and bending stiffness k(c).
      At high aspiration pressure and small external force, the red cell contour can be
      accurately modeled as a sphere, but at low aspiration pressure and large external
      force, the contour deviates from a sphere and may affect the calculation. Based
      on an energy balance and numerical calculations of the cell contour, values of
      the membrane bending stiffness k(c) = 2.0 x 10(-19) Nm and the separation work
      per unit area W(sk) = 0.06 mJ/m2 were obtained.

PMID- 9168043
TI  - An electrochemical approach of the redox behavior of water insoluble ubiquinones
      or plastoquinones incorporated in supported phospholipid layers.
AB  - Physiological mole fractions of long isoprenic chain ubiquinone (UQ[10]) and
      plastoquinone (PQ9) were incorporated inside a supported bilayer by vesicle
      fusion. The template of the bilayer was an especially designed microporous
      electrode that allows the direct electrochemistry of water insoluble molecules in
      a water environment. The artificial structure, made by self-assembly procedures,
      consisted of a bilayer laterally in contact with a built-in gold electrode at
      which direct electron transfers between the redox heads of the quinones molecules
      and the electrode can proceed. The mass balances of quinone and lipid in the
      structure were determined by radiolabeling and spectrophotometry. A dimyristoyl
      phosphatdylcholine stable surface concentration of 250 +/- 50 pmol x cm(-2),
      unaffected by the presence of the quinone, was measured in the fluid monolayer.
      The mole fraction of quinone was between 1 and 3 mol%, remaining unchanged when
      going from the vesicles to the supported layers. The lipid molecules and the
      quinone pool were both laterally mobile, and cyclic voltammetry was used to
      investigate the redox properties of UQ10 and PQ9 over a wide pH range. Below pH
      12, the two electrons-two protons electrochemical process at the gold electrode
      appeared under kinetic control. Thus all thermodynamic deductions must be
      anchored in the observed reversibility of the quinone/hydroquinol anion
      transformation at pH > 13. Within the experimental uncertainty, the standard
      potentials and the pK(a)'s of the pertinent redox forms of UQ10 and PQ9 were
      found to be essentially identical. This differs slightly from the literature in
      which the constants were deduced from the studies of model quinones in mixed
      solvents or of isoprenic quinones without a lipidic environment.

PMID- 9168045
TI  - Probing the ethanol-induced chain interdigitations in gel-state bilayers of mixed
      chain phosphatidylcholines.
AB  - Using high-resolution differential scanning calorimetry (DSC), we have studied
      the effects of ethanol concentrations, [EtOH], on the main phase transition
      temperatures (T[m]) of the following mixed-chain phosphatidylcholines (PCs):
      C(15):C(17)PC, C(17):C(15)PC, and C(12):C(20)PC. These lipids have a common
      molecular weight; however, their apparent acyl chain-length differences between
      the sn-1 and sn-2 acyl chains, delta C, are distinctively different. The delta C
      values for these three mixed-chain PCs are, respectively, 0.5, 3.5, and 6.5 C-C
      bond lengths. DSC results show that the T(m) profiles for C(15):C(17)PC and
      C(17):C(15)PC bilayers in the plot of T(m) versus [EtOH] are V-shaped biphasic
      curves, with the minimum T(m) occurring at 50 and 73 mg/ml of ethanol,
      respectively. In contrast, the C(12):C(20)PC bilayer exhibits a nearly linear
      decrease in T(m) with increasing [EtOH]. In addition, x-ray diffraction
      experiments were also performed to assess the structural changes of these three
      mixed-chain PCs in the gel-state bilayers, at 20 degrees C, in response to high
      concentrations of ethanol. X-ray diffraction data indicate that, in the absence
      of ethanol, these three lamellar lipids are all packed in the normal (L beta')
      gel phase in aqueous media. In the presence of 120 mg/ml of ethanol, however, the
      C(15):C(17)PC and C(17):C(15)PC lamellae are packed in the fully interdigitated
      (L beta[I]) gel phase. The V-shaped T(m) curves detected calorimetrically for
      these two lipids in response to [EtOH] can thus be explained by the ethanol
      induced L beta' --> L beta[I] isothermal phase transition. Interestingly, the
      results of x-ray diffraction study reveal, for the first time, that an ethanol
      induced L beta' --> L(MI) (mixed interdigitated phase) isothermal phase
      transition occurs in the gel-state bilayer of highly asymmetrical C(12):C(20)PC.
      Therefore, the chain asymmetry is recognized to play an important role in the
      ethanol-induced chain interdigitation at T < T(m).

PMID- 9168044
TI  - Escherichia coli diacylglycerol kinase: a case study in the application of
      solution NMR methods to an integral membrane protein.
AB  - Diacylglycerol kinase (DAGK) is a 13-kDa integral membrane protein that spans the
      lipid bilayer three times and which is active in some micellar systems. In this
      work DAGK was purified using metal ion chelate chromatography, and its structural
      properties in micelles and organic solvent mixtures studies were examined,
      primarily to address the question of whether the structure of DAGK can be
      determined using solution NMR methods. Cross-linking studies established that
      DAGK is homotrimeric in decyl maltoside (DM) micelles and mixed micelles. The
      aggregate detergent-protein molecular mass of DAGK in both octyl glucoside and DM
      micelles was determined to be in the range of 100-110 kDa-much larger than the
      sum of the molecular weights of the DAGK trimers and the protein-free micelles.
      In acidic organic solvent mixtures, DAGK-DM complexes were highly soluble and
      yielded relatively well-resolved NMR spectra. NMR and circular dichroism studies
      indicated that in these mixtures the enzyme adopts a kinetically trapped
      monomeric structure in which it irreversibly binds several detergent molecules
      and is primarily alpha-helical, but in which its tertiary structure is largely
      disordered. Although these results provide new information regarding the native
      oligomeric state of DAGK and the structural properties of complex membrane
      proteins in micelles and organic solvent mixtures, the results discourage the
      notion that the structure of DAGK can be readily determined at high resolution
      with solution NMR methods.

PMID- 9168046
TI  - Dichroic ratios in polarized Fourier transform infrared for nonaxial symmetry of
      beta-sheet structures.
AB  - The transition moments for the amide bands from beta-sheet peptide structures
      generally do not exhibit axial symmetry about the director in linearly polarized
      Fourier transform infrared (FTIR) measurements on oriented systems. The angular
      dependences of the dichroic ratios of the amide bands are derived for beta-sheet
      structures in attenuated total reflection (ATR) and polarized transmission
      experiments on samples that are oriented with respect to the normal to the
      substrate and are randomly distributed with respect to the azimuthal angle in the
      plane of the orienting substrate. The orientational distributions of both the
      beta-strands and the beta-sheets are considered, and explicit expressions are
      given for the dichroic ratios of the amide I and amide II bands. The dichroic
      ratio of the amide II band, which is parallel polarized, can yield the
      orientation of the beta-strands directly, but to specify the orientations of the
      beta-sheets completely requires measurement of the dichroic ratios of both the
      amide I and amide II bands, or generally two bands with parallel and
      perpendicular polarizations. A random distribution in tilt of the planes of the
      beta-sheets does not give rise to equal dichroic ratios for bands with
      perpendicular and parallel polarizations, such as the amide I and amide II bands.
      The results are applied to previous ATR and polarized transmission FTIR
      measurements on a potassium channel-associated peptide, the Escherichia coli
      outer membrane protein OmpA, and the E. coli OmpF porin protein in oriented
      membranes.

PMID- 9168047
TI  - Exchange of ATP for ADP on high-force cross-bridges of skinned rabbit muscle
      fibers.
AB  - The contractile properties of rabbit skinned muscle fibers were studied at 1-2
      degrees C in different concentrations of MgATP and MgADP. Double-reciprocal plots
      of maximum velocity against MgATP concentration at different MgADP concentrations
      all extrapolated to the same value. This finding suggests that MgATP and MgADP
      compete for the same site on the cross-bridge, and that the exchange of MgATP for
      MgADP occurs without a detectable step intervening. The K(m) for ATP was 0.32 mM.
      The K(i) for MgADP was 0.33 mM. Control experiments suggested that the tortuosity
      of diffusion paths within the fibers reduced the radial diffusion coefficients
      for reactants about sixfold. Increasing MgADP from 0.18 to 2 mM at 5 mM ATP or
      lowering MgATP from 10 to 2 mM at 0.18 mM MgADP, respectively, increased
      isometric force by 25% and 23%, increased stiffness by 10% and 20%, and decreased
      maximum velocity by 35% and 31%. Two mechanisms appeared to be responsible. One
      detained bridges in high-force states, where they recovered from a length step
      with a slower time course. The other increased the fraction of attached bridges
      without altering the kinetics of their responses, possibly by an increased
      activation resulting from cooperative effects of the detained, high-force
      bridges. The rigor bridge was more effective than the ADP-bound bridge in
      increasing the number of attached bridges with unaltered kinetics.

PMID- 9168048
TI  - AM-loading of fluorescent Ca2+ indicators into intact single fibers of frog
      muscle.
AB  - The AM loading of a number of different fluorescent Ca2+ indicators was compared
      in intact single fibers of frog muscle. Among the 13 indicators studied, loading
      rates (the average increase in the fiber concentration of indicator per first 60
      min of loading) varied approximately 100-fold, from approximately 3 microM/h to
      >300 microM/h (16 degrees C). Loading rates were strongly dependent on the
      molecular weight of the AM compounds, with the rate increasing steeply as
      molecular weight decreased below approximately 850. Properties of delta F/F (the
      Ca2(+)-related fluorescence signal observed with fiber stimulation) were also
      measured in AM-loaded fibers and compared with those previously reported for
      fibers microinjected with indicator. In general, the time course of delta F/F was
      very similar with AM-loading and microinjection; however, the amplitude of delta
      F/F was usually smaller with AM-loading. There was a strong correlation between
      the rate of indicator loading and the value of the parameter f (the ratio of the
      amplitude of delta F/F in AM-loaded versus microinjected fibers). For indicators
      with small loading rates (<10 microM/h, N = 5), f values were generally small (<
      or =0.4, N = 4); whereas with large loading rates (>100 microM/h, N = 4), f
      values were large (> or =0.8, N = 4). This suggests that, with any AM indicator,
      a small concentration may associate nonspecifically with the fiber (either the
      indicator is incompletely de-esterified or, if completely de-esterified, not
      located in the myoplasmic compartment). If the loaded concentration is small, the
      nonspecific indicator will present a significant source of error in the
      estimation of [Ca2+]i.

PMID- 9168049
TI  - Polarized Raman spectroscopy of double-stranded RNA from bacteriophage phi6:
      local Raman tensors of base and backbone vibrations.
AB  - Raman tensors for localized vibrations of base (A, U, G, and C), ribose and
      phosphate groups of double-stranded RNA have been determined from polarized Raman
      measurements on oriented fibers of the genomic RNA of bacteriophage phi6.
      Polarized Raman intensities for which electric vectors of both the incident and
      scattered light are polarized either perpendicular (I[bb]) or parallel (I[cc]) to
      the RNA fiber axis have been obtained by Raman microspectroscopy using 514.5-nm
      excitation. Similarly, the polarized Raman components, I(bc) and I(cb), for which
      incident and scattered vectors are mutually perpendicular, have been obtained.
      Spectra collected from fibers maintained at constant relative humidity in both
      H2O and D2O environments indicate the effects of hydrogen-isotopic shifts on the
      Raman polarizations and tensors. Novel findings are the following: 1) the intense
      Raman band at 813 cm(-1), which is assigned to phosphodiester (OPO) symmetrical
      stretching and represents the key marker of the A conformation of double-stranded
      RNA, is characterized by a moderately anisotropic Raman tensor; 2) the prominent
      RNA band at 1101 cm(-1), which is assigned to phosphodioxy (PO2-) symmetrical
      stretching, also exhibits a moderately anisotropic Raman tensor. Comparison with
      results obtained previously on A, B, and Z DNA suggests that tensors for
      localized vibrations of backbone phosphodiester and phosphodioxy groups are
      sensitive to helix secondary structure and local phosphate group environment; and
      3) highly anisotropic Raman tensors have been found for prominent and well
      resolved Raman markers of all four bases of the RNA duplex. These enable the use
      of polarized Raman spectroscopy for the determination of purine and pyrimidine
      base residue orientations in ribonucleoprotein assemblies. The present
      determination of Raman tensors for dsRNA is comprehensive and accurate.
      Unambiguous tensors have been deduced for virtually all local vibrational modes
      of the 300-1800 cm(-1) spectral interval. The results provide a reliable basis
      for future evaluations of the effects of base pairing, base stacking, and
      sequence context on the polarized Raman spectra of nucleic acids.

PMID- 9168050
TI  - Kinetic analysis of specificity of duplex DNA targeting by homopyrimidine peptide
      nucleic acids.
AB  - A simple theoretical analysis shows that specificity of double-stranded DNA
      (dsDNA) targeting by homopyrimidine peptide nucleic acids (hpyPNAs) is a
      kinetically controlled phenomenon. Our computations give the optimum conditions
      for sequence-specific targeting of dsDNA by hpyPNAs. The analysis shows that, in
      agreement with the available experimental data, kinetic factors play a crucial
      role in the selective targeting of dsDNA by hpyPNAs. The selectivity may be
      completely lost if PNA concentration is too high and/or during prolonged
      incubation of dsDNA with PNA. However, quantitative estimations show that the
      experimentally observed differences in the kinetic constants for hpyPNA binding
      with the correct and mismatched DNA sites are sufficient for sequence-specific
      targeting of long genomic DNA by hpyPNAs with a high yield under appropriate
      experimental conditions. Differential dissociation of hpyPNA/dsDNA complexes is
      shown to enhance the selectivity of DNA targeting by PNA.

PMID- 9168051
TI  - Potential of mean force treatment of salt-mediated protein crystallization.
AB  - In the initial stages of crystallization of proteins, monomers aggregate rapidly
      and form nuclei and large fractal clusters, as previously shown by dynamic light
      scattering experiments (Georgalis, Y., J. Schuler, J. Frank, D. M. Soumpasis, and
      W. Saenger. 1995. Protein crystallization screening through scattering
      techniques. Adv. Colloid Interface Sci. 58:57-86). In this communication we
      initiate an effort to understand the effective interactions controlling charged
      protein aggregation and crystallization using the potential of mean force (PMF)
      theory. We compute the PMFs of the system lysozyme-water-NaCl within the
      framework of the hypernetted chain approximation for a wide range of protein and
      salt concentrations. We show that the computed effective interactions can
      rationalize the experimentally observed aggregation behavior of lysozyme under
      crystallization conditions.

PMID- 9168052
TI  - A 133Cs nuclear magnetic resonance study of endothelial Na(+)-K(+)-ATPase
      activity: can actin regulate its activity?
AB  - Using (133)Cs+ NMR, we developed a technique to repetitively measure, in vivo,
      Na(+)-K(+)-ATPase activity in endothelial cells. The measurements were made
      without the use of an exogenous shift reagent, because of the large chemical
      shift of 1.36 +/- 0.13 ppm between intra- and extracellular Cs+. Intracellularly
      we obtained a spin lattice relaxation time (T1) of 2.0 +/- 0.3 s, and
      extracellular T1 was 7.9 +/- 0.4 s. Na(+)-K+ pump activity in endothelial cells
      was determined at 12 +/- 3 nmol Cs+ x min(-1) x (mg Prot)[-1] under control
      conditions. When intracellular ATP was depleted by the addition of 5 mM 2-deoxy-D
      glucose (DOG) and NaCN to about 5% of control, the pump rate decreased by 33%.
      After 80 min of perfusion with 5 mM DOG and NaCN, reperfusion with control medium
      rapidly reestablished the endothelial membrane Cs+ gradient. Using (133)Cs+ NMR
      as a convenient tool, we further addressed the proposed role of actin as a
      regulator of Na(+)-K+ pump activity in intact cells. Two models of actin
      rearrangement were tested. DOG caused a rearrangement of F-actin and an increase
      in G-actin, with a simultaneous decrease in ATP concentration. Cytochalasin D,
      however, caused an F-actin rearrangement different from that observed for DOG and
      an increase in G-actin, and cellular ATP levels remained unchanged. In both
      models, the Na(+)-K(+)-pump activity remained unchanged, as measured with (133)Cs
      NMR. Our results demonstrate that (133)Cs NMR can be used to repetitively measure
      Na(+)-K(+)-ATPase activity in endothelial cells. No evidence for a regulatory
      role of actin on Na(+)-K(+)-ATPase was found.

PMID- 9168053
TI  - Fluorescence, polarized fluorescence, and Brewster angle microscopy of palmitic
      acid and lung surfactant protein B monolayers.
AB  - Fluorescence, polarized fluorescence, and Brewster angle microscopy reveal that
      human lung surfactant protein SP-B and its amino terminus (SP-B[1-25]) alter the
      phase behavior of palmitic acid monolayers by inhibiting the formation of
      condensed phases and creating a new fluid protein-rich phase. This fluid phase
      forms a network that separates condensed phase domains at coexistence and
      persists to high surface pressures. The network changes the monolayer collapse
      mechanism from heterogeneous nucleation/growth and fracturing processes to a more
      homogeneous process through isolating individual condensed phase domains. This
      results in higher surface pressures at collapse, and monolayers easier to
      respread on expansion, factors essential to the in vivo function of lung
      surfactant. The network is stabilized by a low-line tension between the
      coexisting phases, as confirmed by the observation of extended linear domains, or
      "stripe" phases, and a Gouy-Chapman analysis of protein-containing monolayers.
      Comparison of isotherm data and observed morphologies of monolayers containing SP
      B(1-25) with those containing the full SP-B sequence show that the shortened
      peptide retains most of the native activity of the full-length protein, which may
      lead to cheaper and more effective synthetic replacement formulations.

PMID- 9168054
TI  - Characterization of electric-pulse-induced permeabilization of porcine skin using
      surface electrodes.
AB  - We measured the transient and long-term changes of permeability of full-thickness
      porcine skin after the application of a single or a train of electric pulses, as
      the basis for optimization of the electrical parameters for enhancing transdermal
      drug or gene delivery by electroporation. Two electrodes were attached to the
      stratum corneum of excised skin for transdermal electric pulse delivery and
      impedance measurement. Both transient and long-term permeabilization were found
      to be dependent on the electrical exposure dose, i.e., the product of pulse
      voltage and cumulative pulsing (exposure) time. Skin resistance dropped to about
      20% of its prepulsing value when pulsed beyond a critical dosage of 0.4 V-s (with
      20-40 V across each skin path), but recovered rapidly within seconds after the
      pulse. Long-term permeabilization of the skin required repeated pulsing with a
      minimum potential of 160 V (80 V across each skin path). The maximum long-term
      resistance drop, to 35% of the initial value, required a dose greater than 200 V
      s, recovering slowly and seldom completely in tens of minutes to hours. The
      decrease and recovery of the resistance were dependent on the frequency and pulse
      length only for low-dose electrical exposure.

PMID- 9168055
TI  - Micropipette aspiration on the outer hair cell lateral wall.
AB  - The mechanical properties of the lateral wall of the guinea pig cochlear outer
      hair cell were studied using the micropipette aspiration technique. A fire
      polished micropipette with an inner diameter of approximately 4 microm was
      brought into contact with the lateral wall and negative pressure was applied. The
      resulting deformation of the lateral wall was recorded on videotape and subjected
      to morphometric analysis. The relation between the length of the aspirated
      portion of the cell and aspiration pressure is characterized by the stiffness
      parameter, K(s) = 1.07 +/- 0.24 (SD) dyn/cm (n = 14). Values of K(s) do not
      correlate with the original cell length, which ranges from 29 to 74 microm.
      Theoretical analysis based on elastic shell theory applied to the experimental
      data yields an estimate of the effective elastic shear modulus, mu = 15.4 +/- 3.3
      dyn/cm. These data were obtained at subcritical aspiration pressures, typically
      less than 10 cm H2O. After reaching a critical (vesiculation) pressure, the
      cytoplasmic membrane appeared to separate from the underlying structures, a
      vesicle with a length of 10-20 microm was formed, and the cytoplasmic membrane
      resealed. This vesiculation process was repeated until a cell-specific limit was
      reached and no more vesicles were formed. Over 20 vesicles were formed from the
      longest cells in the experiment.

PMID- 9168057
TI  - Nonlamellar packing parameters for diacylglycerols.

PMID- 9168056
TI  - Quantifying rolling adhesion with a cell-free assay: E-selectin and its
      carbohydrate ligands.
AB  - Rolling of neutrophils over stimulated endothelial cells is a prerequisite to
      firm attachment and subsequent transendothelial migration during the inflammatory
      response. The selectin family of adhesion molecules are thought to mediate
      rolling by binding counter-receptors that present carbohydrates, such as sialyl
      Lewis(x) (sLe[x]). Recently we described a cell-free system for rolling using
      sLe(x)-coated microspheres and E-selectin molecules on inert substrates. We
      showed that sLe(x)-coated microspheres rolled over E-selectin-IgG chimera
      substrates with dynamics that are similar to those of leukocytes rolling over
      stimulated endothelium. In this paper we provide a thorough quantitative
      description of the dynamics of adhesion for this system. We find that particle
      rolling velocity increases with increasing wall shear stress and decreases with
      increasing E-selectin or sLe(x) surface densities. Large changes in the average
      rolling velocity can occur with small changes in sLe(x) or E-selectin density;
      however, rolling velocity is more sensitive to E-selectin surface coverage than
      to the number of sLe(x) molecules on the microspheres. Aided by dimensional
      analysis, we show that decreasing the wall shear stress or increasing either
      receptor (E-selectin) or ligand (sLe[x]) surface coverage results in an
      equivalent decrease in particle rolling velocity. In addition, we find that
      different Lewis carbohydrates are more effective in mediating rolling on E
      selectin, with effectiveness following the trend sialyl Lewis(a) > sialyl
      Lewis(x) >> sulfated Lewis(x) >> Lewis(x). Rolling velocity fluctuated with time
      for all carbohydrate-selectin pairs tested, and the magnitude of the velocity
      fluctuations was linearly proportional to the mean rolling velocity for all
      combinations of E-selectin site density, sLe(x) site density, wall shear stress,
      and carbohydrate chemistry tested.

PMID- 9168058
TI  - Hematology on the African continent.

PMID- 9168059
TI  - JAK3: expression and mapping to chromosome 19p12-13.1.
AB  - We cloned JAK3, the most recently described member of the JAK family of
      intracellular tyrosine kinases, from normal human CD34+ RNA. JAK3 is involved in
      the signal transduction pathways of the IL-2, IL-4, IL7, IL-9, and IL-15
      receptors by association with their common gamma-chain (gamma[c]). JAK3 is
      critical to lymphoid development, as recently established by the linking of
      mutations in JAK3 to a subgroup of patients with SCID and the generation of JAK3
      null mice with severe disruptions in normal lymphocytic development. However,
      JAK3 expression is not restricted to the lymphocytic compartment of bone marrow
      but is found in a wide range of tissues of both hematopoietic and non
      hematopoietic origin. Northern blot analysis indicates that JAK3 is also
      expressed in adult placenta, lung, liver, kidney, pancreas, spleen, thymus,
      ovary, and small intestine. RNAse protection assays and RT-PCR indicate that JAK3
      is expressed in a variety of leukemic-derived hematopoietic cell lines with
      myeloid and/or lymphoid phenotypes. In normal human bone marrow, JAK3 is
      expressed in the CD34+/lineage- fraction, which is highly enriched in
      hematopoietic stem/progenitor cells. In addition, we found a splice variant of
      JAK3 which is formed by the splicing of JAK3 with exon II of the leydig insulin
      like (LEY I-L) hormone. RT-PCR and RNAse protection assay analyses indicate that
      this variant (termed I-JAK3) is normally expressed in almost all hematopoietic
      and non-hematopoietic tissues shown to express JAK3. Using fluorescence in situ
      hybridization we have localized JAK3 to 19p12-13.1, the same region of chromosome
      19 to which the LEY I-L hormone maps (19p12-13.2).

PMID- 9168061
TI  - V-Ha-ras-dependent expression of interleukin-3 mRNA in premalignant PB-3c mast
      cells correlates with the formation of tumors without interleukin-3 gene
      rearrangements.
AB  - Retroviral transduction of v-Ha-ras into the interleukin-3 (IL-3) dependent PB-3c
      cells results in the generation of IL-3 autocrine tumors without (class-I tumors)
      or with (class-II tumors) insertion of endogenous retroviral elements into the IL
      3 locus. In this study, we examined the frequency of both tumor classes arising
      from the IL-3-dependent PB-3c clone 15. This cell line was previously found to be
      unable to suppress IL-3 expression of class-I tumor cells after cell fusion and
      to be highly tumorigenic following ZIP-ras-neo transduction. To identify possible
      preexisting determinants of tumor progression, clone 15 cells were subcloned
      either before or after retroviral ZIP-ras-neo infection and tested for
      tumorigenicity. All 20 sublines with clonal cellular background, but with
      heterogeneous integration sites, were tumorigenic. In contrast, only 12 of 19
      sublines with clonal integration sites formed tumors. None of the 42 tumor cell
      lines analyzed by Southern blotting showed evidence of IL-3 gene rearrangement.
      Only the tumorigenic sublines showed v-Ha-ras transcripts on Northern blots and
      low levels of IL-3 mRNA detectable by RT-PCR, as well as recovery of IL-3
      independent cells after crisis in vitro. Expression of IL-3 mRNA and
      tumorigenicity were found in somatic cell hybrids of clone 15 with 15 v-Ha-ras,
      but not in cell hybrids with the class-I tumor suppressor-positive clone 20 v-Ha
      ras. These data suggest that RT-PCR signals for IL-3 are a predictive marker in
      premalignant cells for the formation of tumors without IL-3 gene rearrangements,
      which depend on v-Ha-ras expression and a cooperating cellular function of
      recessive nature.

PMID- 9168060
TI  - Phenotypic and functional characterization of committed and primitive myeloid and
      lymphoid hematopoietic precursors in human fetal liver.
AB  - We studied the phenotypic and functional properties of colony-forming cells
      (CFCs), primitive long-term culture initiating cells (LTC-ICs) and lymphoid
      precursors present in human fetal liver (FL) and compared these with their adult
      bone marrow (BM) counterparts. FL (7-14-week) cells were selected by fluorescence
      activated cell sorting based on increasing CD34 antigen expression (34+, 34++, or
      34 ), CD38 antigen expression (CD34++/ CD38+, or CD38-), and HLA-DR antigen
      expression (CD34++/ HLA-DR+ or HLA-DR-). 13 +/- 0.6% of FL CD34-positive cells
      were 34 . Significantly more FL CD34++/ cells were CD38- (49 +/- 2.4%) and HLA-DR
      (72 +/- 6.7%) than BM CD34++ cells (6.8 +/- 0.7% CD38- and 13.3 +/- 3.2% HLA-DR
      ). FL and BM CFCs were CD34+/++, CD38+, and HLA-DR+. However, significantly more
      FL CFCs were erythroid (40%) than adult BM CFCs (15%), and FL colonies were
      larger (8111 +/- 738 cells/CFC) than BM colonies (3466 +/- 272 cells/CFC, p <
      0.001). As is seen in adult BM, FL LTC-ICs were CD34++/ CD38-. In contrast to BM
      LTC-ICs, FL LTC-ICs were almost exclusively CD34++/ HLA-DR+. In addition, a
      single FL LTC-IC gave rise to >30 CFCs at 5 weeks compared with only 5 +/- 0.9
      CFCs per LTC-IC from BM. Finally, we demonstrate that the FL CD34++/ /CD38-/HLA
      DR+ population, which contains 3.7% LTC-ICs, also contains primitive lymphoid
      progenitors capable of differentiating into natural killer (NK) cells. In
      conclusion, the phenotype of primitive human FL progenitors such as LTC-IC and
      primitive NK progenitors is CD34++/ /CD38-/HLA-DR+, suggesting that this
      population may contain FL hematopoietic stem cells. The phenotypic
      characterization of FL primitive LTC-ICs and NK progenitors will facilitate
      further studies of the functional properties of these progenitors.

PMID- 9168062
TI  - Corticosteroids alter hematopoiesis in vitro by enhancing human monocyte
      secretion of granulocyte colony-stimulating factor.
AB  - The mechanism of corticosteroid alteration of hematopoiesis is not completely
      elucidated. Employing an endotoxin free system, we examined the mechanisms by
      which hydrocortisone succinate (HCS) enhanced human bone marrow (BM) colony
      forming unit granulocyte-macrophage (CFU-GM) proliferation. Interleukin-1beta (IL
      1) (1 ng/mL), granulocyte-macrophage colony-stimulating factor (GM-CSF) (1
      ng/mL), or the combination, induced minimal CFU-GM proliferation unless HCS was
      added to the cultures (10-25 vs. 80-125 colonies/4x10(5) BM mononuclear cells).
      Supernatants produced by incubating mononuclear cells with IL-1 + GM-CSF +/- HCS
      were examined for their capacity to induce CFU-GM proliferation: IL-1 and/or GM
      CSF failed to induce supernatants capable of supporting CFU-GM proliferation
      unless HCS was present. Analysis of the cytokines produced by mononuclear cell
      subpopulations demonstrated that HCS markedly enhanced IL-1-induced monocyte
      secretion of granulocyte (G)-CSF. Furthermore, the minimal effective
      concentration of IL-1 required to induce G-CSF release was reduced 10-fold (from
      1 to 0.1 ng/mL) and the G-CSF released was increased 5-fold at an IL-1
      concentration of 1 ng/mL. In contrast, IL-1-induced monocyte secretion of tumor
      necrosis factor (TNF) was inhibited by HCS. HCS enhanced G-CSF secretion at
      physiologic concentrations (10 microg/dL), whereas progesterone had no effect.
      HCS alone had no effect on G-CSF secretion or mRNA expression while IL-1+HCS
      resulted in a 3-fold increase in G-CSF mRNA levels. These data suggest for the
      first time that corticosteroids increase secretion of an essential component of
      the lymphohematopoietic cytokine-growth factor system.

PMID- 9168063
TI  - Curcumin, a compound with anti-inflammatory and anti-oxidant properties, down
      regulates chemokine expression in bone marrow stromal cells.
AB  - Chemotactic cytokines or chemokines play an important role in the regulation of
      myelopoiesis. Since the production of chemokines and colony stimulating factors
      (CSFs) by bone marrow stromal cells requires inflammatory conditions, we
      investigated the effect of curcumin, an agent with anti-inflammatory and anti
      oxidant activities, on the expression of monocyte chemoattractant protein-1 (MCP
      1 or MCP-1/JE) and interferon inducible protein-10kD (IP-10) in mouse bone marrow
      stromal cell line +/+-1.LDA11. Both chemokines are readily expressed in stromal
      cells after stimulation with pro-inflammatory interleukin-1alpha (IL-1alpha),
      interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and
      endotoxin lipopolysaccharide (LPS). Curcumin attenuates the levels of MCP-1/JE
      and IP-10 mRNA expression by all of these stimulatory agents. A detailed analysis
      of the regulatory effects of curcumin on chemokine expression by IL-1alpha was
      performed. Curcumin inhibits both chemokine mRNAs in a dose- and time-dependent
      manner. The suppressive effect of curcumin on both mRNAs is reversible with
      complete recovery from suppression within 24 hours after removal of curcumin. The
      suppression of mRNA by curcumin is dependent on de novo synthesis of an
      intermediary protein(s), since suppression is abrogated by concomitant treatment
      with cycloheximide (CHX). Destabilization of mRNA transcripts is not the
      mechanism by which curcumin lowers the levels of mRNA; however, transcripts
      formed in the presence of curcumin are more stable, as indicated by their slower
      degradation kinetics. Run-on transcriptional assays demonstrate that curcumin
      inhibits the transcriptional activity of both genes. Finally, the attenuation of
      chemokine gene expression is associated with decreased production of chemotactic
      activity. Together, these findings indicate that while curcumin may post
      transcriptionally stabilize mRNA transcripts formed in its presence, the overall
      reduction in mRNA levels by curcumin is mediated by inhibition of the
      transcription of chemokine genes.

PMID- 9168064
TI  - Differences in CD34+ cell subpopulations between human bone marrow and
      "mobilized" peripheral blood as determined with counterflow centrifugal
      elutriation.
AB  - Engineering of hematopoietic progenitor cells (HPCs) from bone marrow (BM) or
      "mobilized" peripheral blood (MoPB) is becoming increasingly important.
      Counterflow centrifugal elutriation (CCE) has been used to separate cells on the
      basis of their size. In this study, CCE was applied to evaluate BM and MoPB for
      differences in their HPC populations. Using a standard 4-mL elutriation chamber
      at 2300 rpm, CD34+ cells from BM peaked at a flow rate of 19 mL/minute, with 85%
      of all CD34+ cells recovered from fractions 15-22 mL/minute. The CD34+ cells from
      MoPB, mobilized with chemotherapy and granulocyte colony-stimulating factor (G
      CSF), peaked at 22 mL/minute, with 90% of all CD34+ cells recovered from fraction
      19-26 mL/minute. Colony-forming cells (colony-forming units
      granulocyte/macrophage [CFU-GM] + burst-forming unit-erythroid [BFU-E] +
      multipotent colony-forming units [CFU-GEMMs]) followed the distribution of CD34+
      cells very closely, also with a shift to higher flow-rates for MoPB compared with
      BM. The lower flow-rate fractions of both BM and MoPB contained an increased
      proportion of CD34+ cells that did not express HLA-DR and/or CD38 on their
      surface, suggesting that the earliest CD34+ cells were enriched in the low-flow
      rate fractions. Although CFU-GMs, BFU-Es, and CFU-GEMMs from BM all peaked in the
      same fraction (19 mL/minute), high-proliferative potential colony-forming cells
      (HPP-CFCs) were concentrated in fraction 17 mL/minute, indicating that these
      earlier progenitor cells were slightly smaller. With MoPB, HPP-CFCs did not
      appear to be smaller than BFU-Es or CFU-GEMMs. CCE appears to be an attractive
      method for separating HPCs from BM or MoPB into populations of different
      maturity. Differences in CD34+ cell populations between BM and MoPB may help
      explain the differences in repopulation kinetics observed after transplantation.

PMID- 9168065
TI  - Different macrophage populations develop from embryonic/fetal and adult
      hematopoietic tissues.
AB  - Immunohistochemical and ultrastructural studies have indicated the existence of a
      distinct "fetal macrophage" type, differing from monocyte-derived macrophages. In
      order to characterize macrophages of different ontogenetic origins on the
      molecular level, we examined their surface-marker and marker-gene expression
      patterns. We found that macrophages derived from chicken embryos express the
      lysozyme gene at significantly lower levels than macrophages derived from adult
      chicken. The same was observed when expression of the chicken lysozyme gene was
      analyzed in transgenic mice. In three independent mouse lines, mature macrophages
      derived from embryonic or fetal hematopoietic tissues expressed the transgene at
      drastically lower levels than macrophages derived from the bone marrow, spleen,
      or peritoneal cavity of adult mice. Macrophages obtained by in vitro
      differentiation of mouse embryonic stem cells (a process resembling early
      embryonic hematopoiesis) displayed the embryo-specific low transgene expression
      level. Experiments determining the developmental potential of myeloid precursors
      in culture and immunophenotypic analyses revealed differences between embryo
      derived and adult myeloid progenitor populations. In summary, our results provide
      further evidence for the existence of dissimilar embryonic/fetal and adult
      macrophage types and describe the first molecular marker for their distinction.

PMID- 9168066
TI  - Quiescence, cycling, and turnover in the primitive hematopoietic stem cell
      compartment.
AB  - Continuous oral bromodeoxyuridine (BrdU) administration was used for the non
      invasive measurement of the in vivo cell cycling characteristics of hematopoietic
      stem and progenitor cell populations of increasing maturity, isolated on the
      basis of their relative levels of Rhodamine 123 (Rh) and Hoechst 33342 (Ho)
      fluorescence. The results showed that whereas primitive hematopoietic stem cells
      (PHSCs) are hierarchically ordered on the basis of quiescence, the most primitive
      of these, characterized by their Rh/Ho(dull) phenotype and their capacity for
      long-term hematopoietic reconstitution, are not dormant, but cycle slowly in
      normal steady-state bone marrow (BM). Cell cycle analysis showed that 30 +/- 7%
      of Rh/Ho(dull) PHSCs had cycled and incorporated BrdU following continuous
      administration over 1 week, whereas 60 +/- 14% and 89 +/- 3% of these cells were
      BrdU positive at 4 and 12 weeks, respectively. Linear regression analysis of
      these data showed that Rh/Ho(dull) PHSCs cycle with an average turnover time of
      4.3 weeks (30 days), and a t1/2 (time to 50% cycled) of 2.75 weeks (19 days).

PMID- 9168067
TI  - Confronting change.

PMID- 9168068
TI  - Use of laparoscopic techniques improves outcome from adrenalectomy.
AB  - BACKGROUND: Laparoscopic adrenalectomy is a promising alternative to open
      approaches but safety and efficacy remain unproven. METHODS: A recent experience
      with laparoscopic adrenalectomy at the University of Washington was analyzed for
      efficacy, complications, evolution of technical steps, and clinical outcome.
      RESULTS: Nineteen adrenalectomies were performed in 16 patients with a mean age
      of 52 years. Indications included pheochromocytoma (4), functional adenoma (12),
      and uncontrolled Cushing's disease (3). All patients had computed tomography
      scans. Meta-iodo-benzyl-guanidine (MIBG) or iodocholesterol scans were done in
      selected patients. Three patients had bilateral procedures, 7 were on the left
      and 6 on the right, all via a transperitoneal flank approach. There were no
      conversions and all procedures were successful. Complications included
      subcapsular liver hematomas (2), one transfusion, and a bleeding port site
      requiring repeat laparoscopy. Except for 1 patient with COPD, the mean length of
      stay was 2.9 days. CONCLUSIONS: Laparoscopic adrenalectomy in appropriate
      patients is safe and effective. For endocrine surgeons with advanced laparoscopic
      skills, it should be considered a new standard therapy for benign adrenal tumors.

PMID- 9168069
TI  - Comparison of total versus partial laparoscopic fundoplication in the management
      of gastroesophageal reflux disease.
AB  - BACKGROUND AND METHODS: A comparison of total vs. partial laparoscopic
      fundoplication was conducted in 89 patients from July 92 to June 96. Parameters
      examined were operating room (OR) times, conversion rates, and perioperative
      complications. Patient satisfaction, control of symptoms, and late complications
      were assessed by follow-up at a mean of 6 and 15.4 months. RESULTS: There were
      six conversions to open surgery resulting in 48 laparoscopic total (LTF) and 35
      laparoscopic partial (25 anterior and 10 Toupet) fundoplications (LPF). The
      following results were obtained for each respectively: preop Demeester score 44
      vs. 39; OR time 2.9 vs. 2.5 hours; length of stay 3.6 vs. 4.1 days; early
      morbidity 25% vs. 1%. There were no mortalities. At a mean follow-up of 6 months,
      new-onset dysphagia was present in 8 (17%) vs. 2 (8%), respectively (NS), and
      both total and partial fundoplications appeared successful in controlling
      symptoms (98% vs. 97%). At a mean follow-up of 15.4 months, heartburn was
      resolved or improved in 76% vs. 87% (NS); regurgitation was improved or resolved
      in 93% vs. 93%; and patient satisfaction with the procedure was present in 93%
      vs. 97% (NS). Persistent dysphagia was present in 7.3% vs. 10.3% (NS) of
      patients. Early satiety was present more often in the partial fundoplication
      group (56% vs. 83% P = .03). CONCLUSIONS: Early follow-up suggests equal efficacy
      in controlling symptoms and in achieving patient satisfaction. A 6-month follow
      up suggested a higher incidence of new dysphagia in the total fundoplication
      group; however, at 15-month follow-up there was no significant difference.

PMID- 9168070
TI  - Laparoscopic Hill repair in patients with abnormal motility.
AB  - BACKGROUND: Gastroesophageal reflux is frequently associated with abnormal
      motility in the body of the esophagus. Concern for dysphagia has led surgeons to
      perform less competent procedures in this group, or to avoid surgery altogether.
      The current study was undertaken to evaluate our experience with the laparoscopic
      Hill repair in patients with reflux-associated abnormal motility. METHODS: A
      retrospective review of 338 laparoscopic Hill repairs was performed; 253 patients
      had adequate information for analysis, and 8 patients were excluded because of
      hypertensive motility. The remaining 245 patients were divided into group I (175)
      with normal esophageal body peristalsis, group IIA (37) with moderate
      dysmotility, and group IIB (33) with severe dysmotility. All patients underwent
      standard laparoscopic Hill repair. Follow-up included postoperative manometry and
      24-hour pH studies and interview by an independent physician. Dilation for
      dysphagia was performed when necessary. Statistical analysis was performed using
      the F test. RESULTS: Mean follow-up was 11.0 months (range 1 to 41). Early
      dysphagia (<3 months) occurred in 4.0% of group I patients and 12.9% of group II
      patients. Late dysphagia (>3 months) occurred in 1.1% of group I patients and
      1.4% of group II patients. Postoperative motility returned to normal in 43% of
      group IIB patients studied. Twenty-four hour pH evaluation showed fractional pH
      <4 an average of 4.8% in group I (median 2.1%) and 6.4% in group II (median 4.0%;
      P = 0.57). Patient rating of results was good to excellent in 91.0% with no
      statistical difference between the two groups. No patient required reoperation
      for dysphagia. CONCLUSION: The laparoscopic Hill repair can be safely performed
      in patients with reflux-associated dysmotility, with excellent results. Even
      severely disordered motility will return to normal in a high percentage of cases.
      Manometric control of the repair and secure distal fixation of the
      gastroesophageal junction are advantages. Abnormal motility may be an indication
      for, rather than a contraindication to, laparoscopic Hill repair.

PMID- 9168071
TI  - Video endoscopic transanal-rectal tumor excision.
AB  - BACKGROUND: Transanal resection of benign and selected malignant rectal tumors is
      a well accepted surgical technique. The use of a stereoscopic microsurgical
      technique, as originally described by Buess et al in 1984, has been shown to
      improve the results of standard transanal resection by allowing precise, full
      thickness resections up to 24 cm from the anal verge. Transanal endoscopic
      microsurgery (TEM) has failed to gain widespread popularity for two reasons: The
      proprietary instrument set is expensive and complex ($68,000 and 30 components),
      and the procedure is difficult to master technically. We present our results with
      a modification of the TEM instrument that incorporates a standard laparoscope and
      video camera as well as standard laparoscopic instruments. METHODS: Four surgeons
      have been trained to date. Details of the training curriculum are presented. The
      technique of videoendoscopic transanal tumor resection (VTEM) is described. A
      prospective data base was maintained of all VTEM cases. This was reviewed for
      this study to determine indications, operative times, complications and outcomes.
      RESULTS: Four surgeons performed 27 VTEM cases between August 1994 and June 1996.
      The average age was 69 years and the majority (16) of patients were ASA III. Pre
      op diagnosis was benign polyp in 25 patients and adenocarcinoma in 2. Average
      operating time was 127 minutes (49 to 280 minutes), and was longer during a
      surgeon's first 5 cases and for lesions more than 16 cm from the anal verge.
      Operative problems were rare (4%) and post-op complications (incontinence 2, late
      bleeding 1, adenoma recurrence 1) were seen in 15%. CONCLUSIONS: VTEM can be
      taught successfully to GI and colorectal surgeons using a format similar to that
      used for advanced laparoscopic courses. The use of already available laparoscopes
      and instruments decreases the initial costs of the set-up. Results are good, with
      low rates of complications and recurrence and a very short hospital stay. The
      patient benefits from an effective, minimally invasive alternative to open
      surgery.

PMID- 9168072
TI  - Radioimmunoguided surgery for colorectal cancer.
AB  - BACKGROUND: Improving the survival rate of surgical treatments of cancer depends
      upon accurate staging of disease and the subsequent ability to completely resect
      the lesions. Radioimmunoguided surgery (RIGS) has been employed in the treatment
      of colon and rectal cancer, and a multicenter trial is under way. METHODS: Twenty
      eight patients with either primary or recurrent colorectal cancer were injected
      with the monoclonal antibody CC49 labeled with iodine 125. A hand-held gamma
      detecting probe was used intraoperatively to detect radiolabeled antibody. At
      surgery the patients underwent both traditional and RIGS explorations. RESULTS:
      RIGS detected radiolabeled antibody in 73% (14 of 19) of patients with primary
      colorectal cancer and in 100% (7 of 7) of patients with recurrent disease. Based
      on RIGS, 26% (5 of 19) of patients with primary cancer were upstaged from stage
      I/II to stage III/IV. CONCLUSIONS: Although the final results of this phase III
      trial are incomplete, RIGS appears to provide immediate, valuable information
      that is not available from more conventional methods.

PMID- 9168073
TI  - Gut stromal tumors and their clinical behavior.
AB  - BACKGROUND: Gut stromal tumors (GST) are a group of intramural intestinal tumors
      formerly known as leiomyoma and leiomyosarcoma. To improve the understanding of
      GST behavior, we posed the following questions: What are the clinical sequelae?
      Do size and symptoms correlate? What are the indications for excision? METHODS: A
      retrospective analysis (1988 to 1996) of the clinical course for GST patients was
      completed including long-term follow-up. RESULTS: We found 39 patients with GST
      during the last 8 years. Their average age was 65 years and 59% were male. Tumors
      were found in the small bowel or stomach in 95% of cases. All patients were
      treated by surgical excision. Histologic grading yielded a benign diagnosis in
      77%. Tumors were found incidentally at laparotomy in 41% and had an average size
      of 1.5 cm. In contrast, 59% of GST patients were symptomatic and the average size
      was 6 cm. In these 23 symptomatic patients, gastrointestinal bleeding occurred in
      70%, of which acute hemorrhage was seen in 69-82% of them required transfusion
      and half required emergent operation. Additional findings in the symptomatic
      group included abdominal pain (57%), bowel obstruction (30%), and perforation
      (9%). An average long-term follow-up of 2.5 years was obtained in all patients (n
      = 34, 5 had died of other causes). Local recurrence was seen in 2 patients,
      metastatic disease in 2 other patients, and 30 (88%) were disease free. No
      patient with a GST discovered incidentally has had it recur. CONCLUSION: Gut
      stromal tumors are uncommon yet cause significant patient morbidity. Small GST
      (<2 cm) were asymptomatic but larger GST were usually symptomatic. Most GST
      behaved in a benign fashion after local resection. Due to the frequency of
      serious complications in symptomatic patients, complete excision is recommended
      for GST, even if incidentally discovered.

PMID- 9168074
TI  - A comparison of Medicare reimbursement and results for various imaging-guided
      breast biopsy techniques.
AB  - BACKGROUND: The Medicare population makes up a large proportion of the patients
      who undergo evaluation and treatment of mammographically detected breast lesions.
      In the past, the standard approach for obtaining a histological specimen for
      definitive diagnosis has been wire localization followed by open surgical
      excision (WL-OSE). In recent years, however, imaging-guided large core needle
      biopsy (LCNB) has been investigated as a more cost effective and less invasive
      alternative. METHODS: The authors examined accuracy and reimbursement of
      ultrasound-guided LCNB, stereotactic-guided LCNB, and WL-OSE in 139 Medicare
      patients who demonstrated abnormalities on screening mammograms in 1994 and 1995.
      RESULTS: Ultrasound-guided LCNB was used to diagnose 20% of these cases,
      sterotactic LCNB was used to diagnose 68% of the cases, and the remaining 12%
      were diagnosed using WL-OSE. Histological diagnoses for 54 LCNBs (20 ultrasound
      guided and 34 stereotactic-guided) were 98% accurate when compared with a
      subsequent surgical excision specimen. Ultrasound-guided LCNB was the most cost
      effective approach, showing an average savings of $1,960 per procedure over WL
      OSE and $211 over stereotactic-guided LCNB. Stereotactic-guided LCNB was
      significantly more cost effective than WL-OSE, showing an average savings of
      $1,750 per procedure. CONCLUSIONS: These data indicate imaging-guided LCNB to be
      a reasonable alternative to WL-OSE for definitive histological diagnosis of
      nonpalpable breast lesions. Ultrasound-guided imaging was shown to be applicable
      in 20% of the cases and is the least expensive to the Medicare system. The
      stereotactic approach can be used for a much larger percentage of these patients
      and although not as cost effective as ultrasound, it is considerably more cost
      effective than open excisional biopsy. Both core biopsy techniques provided
      accurate histological diagnoses.

PMID- 9168075
TI  - Changes in serum estrogen levels in women during tamoxifen therapy.
AB  - BACKGROUND: Tamoxifen is considered an antiestrogen against breast cancer, yet it
      has known estrogenic side effects. We hypothesized that long-term administration
      of tamoxifen may significantly increase circulating estrogen levels in women with
      breast cancer. METHODS: Serum dehydroepiandrosterone (DHEA), estrone (E1), and
      estradiol (E2) levels were prospectively measured in 47 breast cancer patients
      before and during tamoxifen therapy for 2 years. Differences in baseline and peak
      hormone levels during treatment were compared, and significance was determined by
      paired Student's t test. RESULTS: Mean DHEA levels increased by 133% from 61 mg/L
      to 142 mg/L (P <0.001) and mean E2 levels increased by 239% from 28 pg/mL to 95
      pg/mL (P <0.05). Mean E1 levels increased by 264% from 42 pg/mL to 153 pg/mL (P =
      0.06). CONCLUSIONS: Long-term tamoxifen therapy can be associated with increased
      serum levels of DHEA, E1, and E2. Elevated serum estrogens may explain
      tamoxifen's estrogenic effects and may represent a mechanism for the development
      of drug resistance.

PMID- 9168076
TI  - The development of a novel intraperitoneal tumor-seeding prophylactic.
AB  - BACKGROUND: Peritoneal tumor dissemination and implantation is a complication of
      both open and laparoscopic oncologic surgery. This study evaluates the efficacy
      of paclitaxel-loaded poly(L-lactic acid) microspheres as prophylaxis against
      intraabdominal tumor seeding. METHODS: 2 x 10(6) 9L glioblastoma cells were
      introduced into the abdominal cavity of Wistar rats. Fifteen minutes later, the
      peritoneal cavity was washed with the experimental solutions, and 2 weeks later
      the presence of tumor implantation was determined. After defining the optimum
      dose of paclitaxel PLA microspheres in a dose-ranging study, the microsphere
      formulation was then compared with conventional paclitaxel in four experimental
      groups (n = 5) as follows: 100 mg of 30% paclitaxel-loaded microspheres; 100 mg
      PLA microspheres; paclitaxel 4.1 mg; and controls receiving no intraabdominal
      therapy. RESULTS: Although carcinomatosis developed in all control animals, none
      in the paclitaxel-loaded microsphere group had biopsy proven cancer. The
      conventional paclitaxel group (3) showed significant toxicity; only 1 animal
      survived and had positive histology. CONCLUSIONS: In this animal model of
      peritoneal carcinomatosis, the paclitaxel-loaded microsphere formulation was more
      effective than conventional paclitaxel in preventing tumor seeding.

PMID- 9168077
TI  - Reinforced versus nonreinforced polytetrafluoroethylene grafts for hemodialysis
      access.
AB  - BACKGROUND: Two major types of polytetrafluoroethylene (PTFE) graft material have
      been available for the past 20 years. Previous studies have suggested that
      nonreinforced PTFE performs better as a hemodialysis conduit than reinforced
      PTFE. We have had experience with both materials for the past 20 years. METHODS:
      This is an outcome study that is based on concurrent and retrospective data.
      Patients were accrued into the study from 1987 to 1995. There were 632 grafts
      that were entered onto a data base and analyzed by a biostatistician. RESULTS:
      Nonreinforced PTFE performed better than reinforced PTFE in every category and
      subgroup. Both mean duration and life-table analysis of the primary patency were
      statistically significant (P < 0.05). The secondary patencies were similar, with
      80% of the nonreinforced and 77% of the reinforced functioning at 1 year. The
      median duration for secondary patency of all grafts was 1,554 days. Diabetic
      patients comprised 50% of the patient population. CONCLUSION: Nonreinforced PTFE
      performs better than reinforced PTFE as a hemodialysis conduit. Until a
      multicentered prospective randomized study can be achieved, a preponderance of
      data suggests that nonreinforced PTFE should be the material of choice for
      hemodialysis access.

PMID- 9168078
TI  - Delayed abdominal closure in the management of ruptured abdominal aortic
      aneurysms.
AB  - BACKGROUND: Resuscitative measures associated with ruptured abdominal aortic
      aneurysm (rAAA) repair may result in massive edema of the bowel, retroperitoneum
      and abdominal wall. The resulting "abdominal compartment syndrome" may compromise
      abdominal closure and may be associated with respiratory, renal and
      cardiovascular deterioration. METHODS: The medical records of 23 patients
      surviving initial operative repair of a rAAA were retrospectively reviewed. Eight
      underwent delayed abdominal closure after early approximation with silastic
      sheets (n = 6) or of the skin only (n = 2). Ultimate outcome, as well as several
      pulmonary and cardiovascular parameters, were compared with patients undergoing
      standard primary fascial closure (n = 15). RESULTS: A trend toward improved
      survival was apparent in the group undergoing delayed abdominal wall closure.
      Significant improvements in oxygenation and mixed venous oxygen saturation were
      observed in these patients, and there were fewer late deaths due to multiple
      organ failure. No patient undergoing delayed abdominal closure developed a graft
      infection. CONCLUSIONS; As in massively resuscitated trauma victims, delayed
      laparotomy closure in rAAA patients may confer a physiologic and survival
      benefit.

PMID- 9168079
TI  - Surgical management of traumatic aortic disruption.
AB  - BACKGROUND: Acute traumatic disruption of the descending thoracic aorta is a life
      threatening injury that requires emergent operative intervention. From May 1988
      to August 1996, 27 patients have undergone surgical repair at our institution.
      METHODS: Diagnosis of aortic disruption was confirmed in all patients by
      aortogram prior to aortic repair. A Gott shunt was used in 24 patients (89%) and
      partial femoral-femoral bypass in 1 patient (4%) for distal perfusion. A clamp
      and-sew technique was used in 2 patients (7%). RESULTS: Mean aortic clamp time
      was 44 +/- 3 minutes (range 22 to 80 minutes) in patients with distal perfusion
      via a Gott shunt. One patient (4%) died within 30 days of aortic repair due to
      multisystem organ failure. Paraplegia occurred in 1 patient (4%). CONCLUSIONS:
      With a disciplined, diagnostic and surgical approach for patients with traumatic
      disruption of the descending thoracic aorta, it is possible to achieve excellent
      outcomes. The use of a Gott shunt is a simple and effective method for distal
      perfusion during the repair of traumatic aortic rupture.

PMID- 9168080
TI  - Beta blockade to prevent atrial dysrhythmias following coronary bypass surgery.
AB  - BACKGROUND: Atrial fibrillation and atrial flutter (AF) frequently complicate
      coronary artery bypass surgery (CABG) and increase hospital stay as well as
      morbidity. Studies of drug prophylaxis to prevent AF with beta-adrenergic
      blocking agents administered in fixed doses have had conflicting results.
      METHODS: One hundred patients were randomized to receive metoprolol or placebo
      following CABG. A dosing algorithm was used to achieve clinically significant
      beta-adrenergic blockade. RESULTS: There was no significant difference between
      the incidence of AF in the metoprolol (24%) and placebo (26%) groups. However,
      the incidence of AF in all patients having CABG at this institution declined over
      the period of the study from 31% to 23% (P < .025), in association with the
      adoption of a continuous technique of cardioplegia delivery. CONCLUSIONS:
      Metoprolol is not efficacious for the prevention of post-CABG AF even when dosage
      is titrated to achieve clinical evidence of beta blockade. It is likely that the
      adoption of a continuous cardioplegia technique caused a reduction in our
      incidence of post-CABG AF.

PMID- 9168081
TI  - Specifications for calculation of risk-adjusted odds of death using trauma
      registry data.
AB  - BACKGROUND: Logistic regression models, with coefficients developed from
      normative populations, can be applied to a trauma registry cohort to predict the
      risk-adjusted frequency of death. Quality of care is judged based on differences
      between predicted and observed mortality frequency. The goal of these analyses
      was to determine if decedents who died in the emergency department had
      independent variables associated with risk of death identical to those who died
      after hospital admission. METHODS: This case-control study is based upon
      decedents in a trauma registry matched to survivors. Backward stepwise linear
      logistic regression models contained independent variables selected to reflect
      patients' status before treatment. RESULTS: Beta coefficients and independent
      variables selected for models of expired emergency department patients were
      different from those of hospital death patients. CONCLUSIONS: To achieve a more
      precise determination of risk-adjusted mortality for injured patients at a trauma
      center, two separate analyses are appropriate: death in emergency department and
      death after hospital admission.

PMID- 9168082
TI  - Ten-year results of the Oregon program with 295 consecutive heart transplants in
      the Pacific Northwest.
AB  - BACKGROUND: The Oregon Cardiac Transplant Program provides a regional service.
      Since December 4, 1985, 284 patients, including 14 children, from Oregon,
      Washington, Idaho, Alaska, and Hawaii, underwent 295 orthotopic heart
      transplantation procedures at the Oregon Health Sciences University. Eleven
      patients underwent transplantations twice. METHODS: Detailed, up-to-date follow
      up data were available on all patients. All patients have been followed up
      prospectively for transplant-related complications. RESULTS: The most common
      recipient diagnoses were coronary artery disease (50%) or idiopathic
      cardiomyopathy (33%). The mean age of the recipients was 48 +/- 15 years (range,
      3 months to 68 years). Donor hearts were retrieved from a procurement area of a
      1,500-mile radius that involved Oregon, Washington, Idaho, Nevada, Utah,
      California, and Canada. The mean donor age was 28 +/- 11 years and the donor
      heart ischemia time was 180 +/- 56 minutes. The median recipient waiting time was
      75 days. Operative mortality was 6%. One-year, 5-year, and 10-year actuarial
      patient survival rates are 86 +/- 2%, 74 +/- 3%, and 59 +/- 5%, respectively. The
      majority of survivors are in very good functional status. CONCLUSIONS: Now, more
      than 10 years into its existence, the Oregon Heart Transplant Program has
      fulfilled its goal of providing a most effective treatment option for patients
      with end-stage heart disease in the region.

PMID- 9168083
TI  - The impact of microsurgical hepatic arterial reconstruction on the outcome of
      liver transplantation for congenital biliary atresia.
AB  - BACKGROUND: Hepatic artery thrombosis (HAT) after liver transplantation for
      biliary atresia (BA) is a serious complication that most often leads to
      retransplantation (re-OLT). The purpose of the present study was: (1) to identify
      risk factors associated with HAT and (2) to analyze the impact of recently
      introduced microsurgical hepatic arterial reconstruction (MHR) on the incidence
      of HAT, subsequent need for re-OLT, and patient survival. METHODS: A
      retrospective review of 194 patients transplanted for BA was performed. One
      hundred and sixty-six patients (group 1) underwent conventional arterial
      reconstruction and 28 (group 2) had MHR. RESULTS: Actuarial survival for patients
      with HAT was significantly worse than for patients without HAT at 1, 2, and 5
      years (71%, 61%, and 57% versus 85%, 85%, and 85%, P = 0.0007). Stepwise logistic
      regression analysis revealed that the risk of HAT correlated best with the type
      of arterial reconstruction (P = 0.007) followed by pretransplant bilirubin
      concentration (P = 0.04) and the number of acute rejection episodes (P = 0.03).
      In group 1, 32 patients developed HAT (19%), and of these, 18 underwent re-OLT
      for HAT. No patient in group 2 developed HAT (P = 0.006 versus group 1). One-year
      actuarial patient survival was 81% in group 1 and 100% in group 2 (P = 0.02).
      CONCLUSIONS: In OLT for BA, (1) the predominant risk factor for HAT is the
      technique of arterial reconstruction, and (2) MHR markedly reduces the incidence
      of HAT and the need for re-OLT while improving patient survival.

PMID- 9168084
TI  - Pancreatic cancer and comparison of a hospital-based tumor registry with a
      National Cancer Data Base.
AB  - BACKGROUND: The Commission on Cancer of the American College of Surgeons has
      called upon institutions providing cancer care to compare practice patterns and
      outcomes with the National Cancer Data Base (NCDB). Using data from the Virginia
      Mason Tumor Registry (VMTR), we sought to compare our pancreatic cancer care
      patterns with those reported nationally, while critically evaluating the accuracy
      and usefulness of our registry. METHODS: A review of the 906 computerized patient
      files in the VMTR from 1973 to 1995 was performed, with more detailed data on
      patients from the last 5 years retrieved from 224 manual abstracts. These data
      were compared with the 1991 NCDB for pancreatic cancer. RESULTS: The percent of
      cases according to AJCC stage in the NCDB (n = 9,715) versus the VMTR (n = 149),
      respectively, with cases of unknown stage excluded, were stage I 22% versus 22%,
      stage II 9% versus 12%, stage III 17% versus 28% (P <0.05) stage IV 52% versus
      38% (P <0.05). One-third of the cases in the VMTR 1991 to 1995 were of unknown
      stage; number of cases with unknown stage for NCDB was 26.6%. The percent of
      surgical procedures for the NCDB (n = 7,802) versus the VMTR (n = 224),
      respectively, was pancreatectomy 14% versus 11%, local excision 1% versus 0%, no
      cancer-directed surgery 83% versus 89% (P <0.05), unknown 2% versus 0% (P <0.05).
      The actuarial relative survival rates for the 1991 NCDB versus 1987 to 1995 VMTR
      was 3-year 18% versus 38%, and 5-year 14% versus 35%. CONCLUSIONS: In comparison
      with the NCDB, VMTR may have fewer stage IV pancreatic cancers, but improvement
      is needed in decreasing the number of patients for whom the stage is unknown, as
      many of these likely represent late stage disease. We have a similar resection
      rate and a higher survival compared with the NCDB, but a mechanism is not in
      place to statistically compare our survival data with those of the NCDB. Even
      though all accredited hospitals are required to have a tumor registry, our data
      were difficult to compare with those of the NCDB because of coding and reporting
      deficiencies and inability to statistically compare survival data. Before our
      practice patterns and outcomes can be compared with national standards, both the
      VMTR and the NCDB must have standardized data collection and better access to the
      data.

PMID- 9168085
TI  - Effectiveness and safety of 100 consecutive parathyroidectomies.
AB  - BACKGROUND AND METHODS: In order to evaluate the indications for operation for
      patients with primary hyperparathyroidism, prospective information was gathered
      on 100 consecutively operated patients from 1991 to 1996. A standard evaluation
      for outcomes and patient satisfaction was instituted. Patients consisted of 73
      women and 27 men. Major symptoms existed in 48 patients, and 52 patients were
      referred to as "asymptomatic" because they fit the National Institutes of Health
      Consensus Development Conference Statement with abnormal laboratory values. The
      pathology was 94 single adenomas, 4 double adenomas, and 2 cases of hyperplastic
      multiglandular disease. RESULTS: All 100 patients had abnormal parathyroids
      removed, resulting in normocalcemia in 97. Three patients had persistent
      hypercalcemia until a second operation removed additional abnormal parathyroids,
      resulting in normocalcemia. No operative complications or mortality occurred.
      Overnight stay occurred in 88 patients. During long-term follow-up of patients,
      only 2 developed recurrent hyperparathyroidism. When asked whether the operation
      improved their health, 94% of patients with major symptoms and 72% of
      asymptomatic patients responded affirmatively. CONCLUSION: Parathyroidectomy is
      an efficient and safe operation with excellent normalization of serum calcium and
      a high rate of patient satisfaction.

PMID- 9168086
TI  - Retrorectus prosthetic mesh repair of midline abdominal hernia.
AB  - BACKGROUND: Midline abdominal hernia is a common problem seen by the general
      surgeon. Recurrence rates are as high as 49% when an autogenous repair is
      performed, and as high as 11% when prosthetic mesh is used as a "bridge" or
      "onlay." METHODS: This study analyzes results of midline abdominal hernia repair
      in 106 cases using prosthetic mesh, in the retrorectus position, as described by
      Stoppa and Wantz. Charts were reviewed, patient satisfaction determined by
      telephone interview, and recurrence rate by physician examination. RESULTS: Major
      systemic complications occurred in 17%. There were no deaths. Eighteen percent
      developed a wound complication, requiring a return to the operating room in 5%.
      There were three recurrences (3.5%). CONCLUSIONS: Retrorectus placement of
      prosthetic mesh in the repair of midline abdominal hernia is effective and
      compares favorably with other methods. Significant complications are low,
      recurrence is rare, and patient satisfaction is high.

PMID- 9168087
TI  - Complications of pyloromyotomy for infantile hypertrophic pyloric stenosis.
AB  - BACKGROUND: Few references exist regarding contemporary complications of
      pyloromyotomy (PM) for infantile hypertrophic pyloric stenosis (IHPS). Therefore,
      we reviewed the frequency and outcome of patients with IHPS who developed
      complications from PM. METHOD: A 25-year retrospective review was performed in
      two populations. The first group included all infants who had a PM for IHPS at
      two pediatric surgery centers. The second group included all infants referred
      from other institutions who developed complications following PM for IHPS.
      RESULTS: Between 1969 and 1994, 901 PMs were performed. Intraoperative
      complications occurred in 40 patients (4%), including 39 duodenal perforations
      and 1 difficult intubation requiring prolonged ventilation. No unrecognized
      duodenal perforations or incomplete PMs were found. Postoperative complications
      developed in 52 patients (6%). The wound infection rate was less than 1%.
      Postoperative vomiting occurred in 31 infants (3%). The mortality rate was 0.1%,
      with 1 death due to sepsis from delayed diagnosis of Hirschsprung's disease.
      During the same study period, 11 patients were referred from other hospitals for
      postoperative complications. Five had persistent vomiting treated successfully
      with expectant management. Six infants needed reoperation: 3 for persistent IHPS,
      1 for gastric outlet obstruction, and 1 for small bowel obstruction secondary to
      adhesions; 1 required wound abscess drainage. CONCLUSION: Pyloromyotomy is not
      without complications. Duodenal perforation should be infrequent, but when it
      occurs, it can usually be readily recognized and treated with minimal morbidity.
      Postoperative vomiting can be managed nonoperatively, but if it persists longer
      than 5 days, radiologic evaluation should be performed. Incomplete PM is uncommon
      and should not occur. A second myotomy is needed when the diagnosis of incomplete
      myotomy is established. A single standard of care should be expected of all
      surgeons who perform PM for IHPS.

PMID- 9168088
TI  - Stereotactic needle core biopsy.

PMID- 9168089
TI  - Cost effectiveness and accuracy of stereotactic breast biopsy.

PMID- 9168090
TI  - The hypertensive lower esophageal sphincter.

PMID- 9168091
TI  - The tension-free hernioplasty in a randomized trial.

PMID- 9168092
TI  - Emergency contrast studies in the surgical patient: the case against barium.

PMID- 9168093
TI  - Abdominal wall hernias with abdominal aortic aneurysmal versus aortoiliac
      occlusive disease.

PMID- 9168094
TI  - Inadvertent perforation of rectum during abdominoperineal resection.

PMID- 9168095
TI  - Isovolemic hemodilution with dextran prevents contrast medium induced impairment
      of pancreatic microcirculation.

PMID- 9168096
TI  - UK redraws medical research funding.

PMID- 9168097
TI  - Forged images lead to German inquiry.

PMID- 9168098
TI  - Company accused over lab data 'theft'.

PMID- 9168100
TI  - Compatibility of Islam and science.

PMID- 9168099
TI  - Ethics of private panels comes under scrutiny.

PMID- 9168101
TI  - Cultivating a cure for blindness.

PMID- 9168102
TI  - DNA repair. A sense-abl response?

PMID- 9168103
TI  - Genome evolution. The mitochondrion that time forgot.

PMID- 9168104
TI  - Alzheimer's disease. Short precursor shortens memory.

PMID- 9168105
TI  - The first genome from the third domain of life.

PMID- 9168106
TI  - Lichens, air pollution and lung cancer.

PMID- 9168107
TI  - Vervet monkeys as travelling salesmen.

PMID- 9168108
TI  - Rhodopsin guides fungal phototaxis.

PMID- 9168109
TI  - Evidence for a clade of nematodes, arthropods and other moulting animals.
AB  - The arthropods constitute the most diverse animal group, but, despite their rich
      fossil record and a century of study, their phylogenetic relationships remain
      unclear. Taxa previously proposed to be sister groups to the arthropods include
      Annelida, Onychophora, Tardigrada and others, but hypotheses of phylogenetic
      relationships have been conflicting. For example, onychophorans, like arthropods,
      moult periodically, have an arthropod arrangement of haemocoel, and have been
      related to arthropods in morphological and mitochondrial DNA sequence analyses.
      Like annelids, they possess segmental nephridia and muscles that are a
      combination of smooth and obliquely striated fibres. Our phylogenetic analysis of
      18S ribosomal DNA sequences indicates a close relationship between arthropods,
      nematodes and all other moulting phyla. The results suggest that ecdysis
      (moulting) arose once and support the idea of a new clade, Ecdysozoa, containing
      moulting animals: arthropods, tardigrades, onychophorans, nematodes,
      nematomorphs, kinorhynchs and priapulids. No support is found for a clade of
      segmented animals, the Articulata, uniting annelids with arthropods. The
      hypothesis that nematodes are related to arthropods has important implications
      for developmental genetic studies using as model systems the nematode
      Caenorhabditis elegans and the arthropod Drosophila melanogaster, which are
      generally held to be phylogenetically distant from each other.

PMID- 9168110
TI  - An ancestral mitochondrial DNA resembling a eubacterial genome in miniature.
AB  - Mitochondria, organelles specialized in energy conservation reactions in
      eukaryotic cells, have evolved from eubacteria-like endosymbionts whose closest
      known relatives are the rickettsial group of alpha-proteobacteria. Because
      characterized mitochondrial genomes vary markedly in structure, it has been
      impossible to infer from them the initial form of the proto-mitochondrial genome.
      This would require the identification of minimally derived mitochondrial DNAs
      that better reflect the ancestral state. Here we describe such a primitive
      mitochondrial genome, in the freshwater protozoon Reclinomonas americana. This
      protist displays ultrastructural characteristics that ally it with the
      retortamonads, a protozoan group that lacks mitochondria. R. americana mtDNA
      (69,034 base pairs) contains the largest collection of genes (97) so far
      identified in any mtDNA, including genes for 5S ribosomal RNA, the RNA component
      of RNase P, and at least 18 proteins not previously known to be encoded in
      mitochondria. Most surprising are four genes specifying a multisubunit,
      eubacterial-type RNA polymerase. Features of gene content together with
      eubacterial characteristics of genome organization and expression not found
      before in mitochondrial genomes indicate that R. americana mtDNA more closely
      resembles the ancestral proto-mitochondrial genome than any other mtDNA
      investigated to date.

PMID- 9168111
TI  - Behavioural stress facilitates the induction of long-term depression in the
      hippocampus.
AB  - The induction of activity-dependent persistent increases in synaptic efficacy,
      such as long-term potentiation (LTP), is inhibited by behavioural stress. The
      question arises whether stress also affects the ability to induce persistent
      decreases in synaptic efficacy, such as long-term depression (LTD). We now report
      that the induction of stable homosynaptic LTD in the CA1 area of the hippocampus
      of awake adult rats is facilitated, rather than inhibited, by exposure to mild
      naturalistic stress. The same stress blocked the induction of LTP. The effects of
      such stress were short lasting: acclimatization to, or removal from, the
      conditions that facilitated LTD induction led to a rapid loss of the ability to
      elicit this form of plasticity. The time window in which LTD could be reliably
      elicited was prolonged by inducing anaesthesia immediately after the stress.
      These data reveal that even brief exposure to mild stress can produce a striking
      shift in the susceptibility to synaptic plasticity in the awake animal.

PMID- 9168112
TI  - Impaired learning and LTP in mice expressing the carboxy terminus of the
      Alzheimer amyloid precursor protein.
AB  - Proteolytic processing of amyloid precursor protein (APP) through an
      endosomal/lysosomal pathway generates carboxy-terminal polypeptides that contain
      an intact beta-amyloid domain. Cleavage by as-yet unidentified proteases releases
      the beta-amyloid peptide in soluble form. In Alzheimer's disease, aggregated beta
      amyloid is deposited in extracellular neuritic plaques. Although most of the
      molecular mechanisms involving beta-amyloid and APP in the aetiology of
      Alzheimer's disease are still unclear, changes in APP metabolism may be important
      in the pathogenesis of the disease. Here we show that transgenic mice expressing
      the amyloidogenic carboxy-terminal 104 amino acids of APP develop, with ageing,
      extracellular beta-amyloid immunoreactivity, increased gliosis and microglial
      reactivity, as well as cell loss in the CA1 region of the hippocampus. Adult
      transgenic mice demonstrate spatial-learning deficits in the Morris water maze
      and in maintenance of long-term potentiation (LTP). Our results indicate that
      alterations in the processing of APP may have considerable physiological effects
      on synaptic plasticity.

PMID- 9168113
TI  - Distinct ATP receptors on pain-sensing and stretch-sensing neurons.
AB  - The initial pain from tissue damage may result from the release of cytoplasmic
      components that act upon nociceptors, the sensors for pain. ATP was proposed to
      fill this role because it elicits pain when applied intradermally and may be the
      active compound in cytoplasmic fractions that cause pain. Moreover, ATP opens
      ligand-gated ion channels (P2X receptors) in sensory neurons and only sensory
      neurons express messenger RNA for the P2X3 receptor. To test whether ATP
      contributes to nociception, we developed a tissue culture system that allows
      comparison of nociceptive (tooth-pulp afferent) and non-nociceptive (muscle
      stretch receptor) rat sensory neurons. Low concentrations of ATP evoked action
      potentials and large inward currents in both types of neuron. Nociceptors had
      currents that were similar to those of heterologously expressed channels
      containing P2X3 subunits, and had P2X3 immunoreactivity in their sensory endings
      and cell bodies. Stretch receptors had currents that differed from those of P2X3
      channels, and had no P2X3 immunoreactivity. These results support the theory that
      P2X3 receptors mediate a form of nociception, but also suggest non-nociceptive
      roles for ATP in sensory neurons.

PMID- 9168114
TI  - Ligands for ErbB-family receptors encoded by a neuregulin-like gene.
AB  - Neuregulins (also called ARIA, GGF, heregulin or NDF) are a group of polypeptide
      factors that arise from alternative RNA splicing of a single gene. Through their
      interaction with the ErbB family of receptors (ErbB2, ErbB3 and ErbB4),
      neuregulins help to regulate cell growth and differentiation in many tissues.
      Here we report the cloning of a second neuregulin-like gene, neuregulin-2. The
      encoded product of the neuregulin-2 gene has a motif structure similar to that of
      neuregulins and an alternative splicing site in the epidermal growth factor(EGF)
      like domain gives rise to two isoforms (alpha and beta). Northern blot and in
      situ hybridization analysis of adult rat tissues indicate that expression of
      neuregulin-2 is highest in the cerebellum, and the expression pattern is
      different from that of neuregulins. Recombinant neuregulin-2beta induces the
      tyrosine-phosphorylation of ErbB2, ErbB3 and ErbB4 in cell lines expressing all
      of these ErbB-family receptors. However, in cell lines with defined combinations
      of ErbBs, neuregulin-2beta only activates those with ErbB3 and/or ErbB4,
      suggesting that signalling by neuregulin-2 is mediated by ErbB3 and/or ErbB4
      receptors.

PMID- 9168115
TI  - Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases.
AB  - The neuregulins (NRGs) are a family of multipotent epidermal-growth-factor-like
      (EGF-like) factors that arise from splice variants of a single gene. They
      influence the growth, differentiation, survival and fate of several cell types.
      We have now discovered a set of new neuregulin-like growth factors, which we call
      neuregulin-2 (NRG-2): these are encoded by their own gene and exhibit a distinct
      expression pattern in adult brain and developing heart. Like NRG-1, the EGF-like
      domain of the new ligands binds to both the ErbB3- and ErbB4-receptor tyrosine
      kinases. However, NRG-2 stimulates different ErbB-receptor tyrosine
      phosphorylation profiles from NRG-1. Our results indicate that NRG-1 and NRG-2
      mediate distinct biological processes by acting at different sites in tissues and
      eliciting different biochemical responses in cells.

PMID- 9168116
TI  - Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response
      to ionizing radiation.
AB  - Ataxia telangiectasia (AT) is a rare human autosomal recessive disorder with
      pleiotropic phenotypes, including neuronal degeneration, immune dysfunction,
      premature ageing and increased cancer risk. The gene mutated in AT, ATM, encodes
      a putative lipid or protein kinase. Most of the human AT patient phenotypes are
      recapitulated in Atm-deficient mice. Cells derived from Atm-/- mice, like those
      from AT patients, exhibit abnormal response to ionizing radiation. One of the
      known responses to ionizing radiation is the activation of a nuclear tyrosine
      kinase encoded by the c-abl proto-oncogene. Ionizing radiation does not activate
      c-Abl in cells from AT patients or in thymocytes or fibroblasts from the Atm
      deficient mice. Ectopic expression of a functional ATM kinase domain corrects
      this defect, as it phosphorylates the c-Abl tyrosine kinase in vitro at Ser 465,
      leading to the activation of c-Abl. A mutant c-Abl with Ser 465 changed to Ala
      465 is not activated by ionizing radiation or ATM kinase in vivo. These findings
      identify the c-Abl tyrosine kinase as a downstream target of phosphorylation and
      activation by the ATM kinase in the cellular response to ionizing radiation.

PMID- 9168117
TI  - Interaction between ATM protein and c-Abl in response to DNA damage.
AB  - The gene mutated in the autosomal recessive disorder ataxia telangiectasia (AT),
      designated ATM (for 'AT mutated'), is a member of a family of
      phosphatidylinositol-3-kinase-like enzymes that are involved in cell-cycle
      control, meiotic recombination, telomere length monitoring and DNA-damage
      response. Previous results have demonstrated that AT cells are hypersensitive to
      ionizing radiation and are defective at the G1/S checkpoint after radiation
      damage. Because cells lacking the protein tyrosine kinase c-Abl are also
      defective in radiation-induced G1 arrest, we investigated the possibility that
      ATM might interact with c-Abl in response to radiation damage. Here we show that
      ATM binds c-Abl constitutively in control cells but not in AT cells. Our results
      demonstrate that the SH3 domain of c-Abl interacts with a DPAPNPPHFP motif
      (residues 1,373-1,382) of ATM. The results also reveal that radiation-induction
      of c-Abl tyrosine kinase activity is diminished in AT cells. These findings
      indicate that ATM is involved in the activation of c-Abl by DNA damage and this
      interaction may in part mediate radiation-induced G1 arrest.

PMID- 9168118
TI  - The dynamics of a pre-mRNA splicing factor in living cells.
AB  - Pre-mRNA splicing is a predominantly co-transcriptional event which involves a
      large number of essential splicing factors. Within the mammalian cell nucleus,
      most splicing factors are concentrated in 20-40 distinct domains called speckles.
      The function of speckles and the organization of cellular transcription and pre
      mRNA splicing in vivo are not well understood. We have investigated the dynamic
      properties of splicing factors in nuclei of living cells. Here we show that
      speckles are highly dynamic structures that respond specifically to activation of
      nearby genes. These dynamic events are dependent on RNA polymerase II
      transcription, and are sensitive to inhibitors of protein kinases and Ser/Thr
      phosphatases. When single genes are transcriptionally activated in living cells,
      splicing factors leave speckles in peripheral extensions and accumulate at the
      new sites of transcription. We conclude that one function of speckles is to
      supply splicing factors to active genes. Our observations demonstrate that the
      interphase nucleus is far more dynamic in nature than previously assumed.

PMID- 9168119
TI  - Dimeric association and segmental variability in the structure of human CD4.
AB  - CD4 is a co-receptor in the cellular immune response. It increases the avidity of
      association between a T cell and an antigen-presenting cell by interacting with
      non-polymorphic portions of the complex between class II major histocompatibility
      complex (MHC) and T-cell receptor (TCR) molecules, and it contributes directly to
      signal transduction through its cytoplasmic association with the lymphocyte
      kinase Lck. CD4 also serves as the high-affinity receptor for cellular attachment
      and entry of the human immunodeficiency virus (HIV). The extracellular portion of
      CD4 comprises four immunoglobulin-like domains (D1-D4). This part of human CD4
      (residues 1-369) has been characterized as a recombinant soluble protein (sCD4),
      and crystal structures have been described for the human D1D2 fragment and for
      the rat D3D4 fragment. We have now determined the structures of intact sCD4 in
      three crystal lattices. These structures have a hinge-like variability at the
      D1D2 to D3D4 junction that might be important in immune recognition and HIV
      fusion, and a common dimeric association through D4 domains. Dynamic light
      scattering measurements and chemical crosslinking of sCD4 corroborate
      dimerization at high protein concentration. We suggest that such dimers mayhave
      relevance as mediators of signal transduction in T cells.

PMID- 9168120
TI  - Nucleotide sequence and expression of the organomercurial-resistance determinants
      from a Pseudomonas K-62 plasmid pMR26.
AB  - pMRA17 cloned from Pseudomonas K-62 plasmid pMR26 specified the resistance to
      both organic and inorganic mercurials. DNA sequence of this broad-spectrum
      resistant mer operon was determined. The 5504-bp sequence includes six open
      reading frames (ORFs), five of which were identified as merR, merT, merP, merA
      and merB in order by analysis of deletion mutants and by comparison with the DNA
      and amino acid (aa) sequences of previously sequenced mer operons. The merB
      encoding organomercurial lyase showed a less identity than the other mer genes
      with those from other broad-spectrum resistance operons. The remaining ORF named
      merE, located between merA and merB, had no significant homology with the
      published mer genes and seemed to be a new gene which may involve in
      phenylmercury resistance. Induction experiments and maxicell analyses of the mer
      polypeptides revealed that pMRA17 mer operon expressed mercurial-inducible
      phenotype and the merB and merE as well as the merA were under the control of
      MerR which could activate not only by mercuric ion but also by organomercurials.

PMID- 9168121
TI  - A bacterial cloning vector using a mutated Aequorea green fluorescent protein as
      an indicator.
AB  - The bacterial cloning vector, pGreenscript A, derived from the mutated Aequorea
      green fluorescent protein (GFP-S65A) gene, when expressed in E. coli produced
      colonies that showed yellow color under daylight and strong green fluorescence
      under long-wave ultraviolet light. The vector was used to select for inserted
      foreign genes based on the loss of the yellow color/green fluorescence of E. coli
      cells caused by the insertional inactivation of GFP production.

PMID- 9168122
TI  - Cloning and characterization of the gene (empV) encoding extracellular
      metalloprotease from Vibrio vulnificus.
AB  - A gene (empV) encoding the extracellular metalloprotease of Vibrio vulnificus CKM
      1 has been cloned and sequenced. When the empV gene was expressed in minicells, a
      unique peptide of approx. 46 kDa was identified. Protease activity staining
      experiments also indicated a similar M(r) for the protease. The empV gene product
      (EmpV) is secreted into the periplasm of Escherichia coli, but not out of it. The
      crude enzyme prepared from the periplasmic fraction of recombinant E. coli was
      inhibited by a metalloprotease inhibitor and Zn2+ is essential for its protease
      activity. Nucleotide sequence analysis predicted a single open reading frame
      (ORF) of 1818 bp encoding a 606 amino acid (aa) polypeptide, with a potential 24
      aa signal peptide followed by a long 'pro' sequence consisting of 172 aa. The N
      terminal 20 aa sequence for the elastolytic protease (EepV), purified from the
      culture supernatant of V. vulnificus ATCC 29307, completely identified the
      beginning of the predicted mature protein within the deduced aa sequence except
      for 1 aa residue difference. The estimated pI and molecular weight of the
      predicted mature protein were 5.86 and 44.3 kDa, respectively, which are nearly
      identical to those of V. vulnificus L-180 extracellular neutral metalloprotease
      (EnmV) and of strain ATCC 29307 EepV. The estimated molecular weight also closely
      matches that determined by SDS-PAGE analysis of the minicells and by protease
      activity staining. The deduced aa sequence of EmpV showed high homology to V.
      anguillarum metalloprotease (EmpA), V. cholerae HA/protease (HprC), and V
      proteolyticus neutral protease (NprP), particularly with respect to active-site
      residues, zinc-binding residues, and cysteine residues.

PMID- 9168124
TI  - The mouse uracil-DNA glycosylase gene: isolation of cDNA and genomic clones and
      mapping ung to mouse chromosome 5.
AB  - Uracil-DNA glycosylase (UDG) is the enzyme responsible for the first step in the
      base-excision repair pathway that specifically removes uracil from DNA. Here we
      report the isolation of the cDNA and genomic clones for the mouse uracil-DNA
      glycosylase gene (ung) homologous to the major placental uracil-DNA glycosylase
      gene (UNG) of humans. The complete characterization of the genomic organization
      of the mouse uracil-DNA glycosylase gene shows that the entire mRNA coding region
      for the 1.83-kb cDNA of the mouse ung gene is contained in an 8.2-kb SstI genomic
      fragment which includes six exons and five introns. The cDNA encodes a predicted
      uracil-DNA glycosylase (UDG) protein of 295 amino acids (33 kDa) that is highly
      similar to a group of UDGs that have been isolated from a wide variety of
      organisms. The mouse ung gene has been mapped to mouse chromosome 5 using
      fluorescence in situ hybridization (FISH).

PMID- 9168123
TI  - Cloning, sequencing and expressing the carotenoid biosynthesis genes, lycopene
      cyclase and phytoene desaturase, from the aerobic photosynthetic bacterium
      Erythrobacter longus sp. strain Och101 in Escherichia coli.
AB  - Two genes which encode the enzymes lycopene cyclase and phytoene desaturase in
      the aerobic photosynthetic bacterium Erythrobacter longus sp. strain Och101 have
      been cloned and sequenced. The gene for lycopene cyclase, designated crtY, was
      expressed in a strain of Escherichia coli which contained the crtE, B, I and Z
      genes encoding geranylgeranyl pyrophosphate synthase, phytoene synthase, phytoene
      desaturase, and beta-carotene hydroxylase, respectively. As a result, zeaxanthin
      production was observed in E. coli transformants. In addition, expression of the
      E. longus gene crtI for phytoene desaturase in E. coli containing crtE and B
      resulted in the accumulation of lycopene in transformants. Zeaxanthin and
      lycopene were also determined by mass spectrum. Nucleotide sequence similarities
      between E. longus crtY gene and other microbial lycopene cyclase genes are 40.2%
      (Erwinia herbicola), 37.4% (Erwinia uredovora) and 22.9% (Synechococcus sp.), and
      those between phytoene desaturase genes are 50.3% (E. herbicola), 54.7% (E.
      uredovora) and 39.6% (Rhodobacter capsulatus).

PMID- 9168125
TI  - Sequence analysis and tissue expression of a non-Bohr beta-globin cDNA from
      Atlantic salmon.
AB  - The presence of a haemoglobin protein which does not exhibit a Bohr effect has
      been found only in fish living in fast flowing waters. We report the cloning of
      the first non-Bohr effect beta-globin cDNA from an adult Atlantic salmon kidney
      bank. Nucleotide sequence analysis of this cDNA shows that the predicted beta
      globin peptide comprises 147 amino acids with a calculated molecular mass of 15
      975 Da and an overall amino acid homology of 40 to 50% to higher vertebrates and
      60-90% to fish sequences. This sequence confirms the important amino acid
      residues which are changed thus causing loss of the Bohr effect [Powers, D.A. and
      Edmunson, A.B. (1972) Multiple hemoglobins of catostomid fish. J. Biol. Chem.
      247, 6686-6693; Brunori, M. (1975) Molecular adaptation to physiological
      requirements: the hemoglobin system of trout. Curr. Topics Cell. Regul. 9, 1-39].
      This loss allows the haemoglobin protein to have a higher oxygen affinity, as it
      does not release oxygen when the pH of the surrounding environment decreases,
      which is an important ability for the fish in times of stress.

PMID- 9168126
TI  - Sequence analysis of gene 3, gene 4 and gene 5 of avian infectious bronchitis
      virus strain CU-T2.
AB  - We have previously reported the nucleotide sequences of gene 2 (spike (S) protein
      gene), gene 6 (nucleocapsid (N) protein gene), and the 3' end untranslated region
      of a novel avian infectious bronchitis virus (IBV) strain, CU-T2 [Jia et al.
      (1995) Arch. Virol. 140, 259 271]. In the present report we describe the
      sequences of the remaining genes of this strain (gene 3, 4 and 5) with the
      exception of gene 1 (RNA polymerase gene). Gene 3 contained three open reading
      frames (ORFs), 3a, 3b and 3c of 174, 195 and 282 nucleotides (nt), respectively.
      Gene 4 (membrane (M) protein gene) consisted of 749 nt with a single ORF of 687
      nt. Gene 5 contained two ORFs, 5a and 5b, with 198 and 249 nt, respectively.
      Thus, in total, there were 7349 nt from the 5' end of S protein gene to the 3'
      end of the CU-T2 genome. The overall nt sequence homologies between gene 3, 4,
      and 5 of CU-T2 and those of other strains were between 84.1-90.8%, 85.8-88.8% and
      90.4 96.4%, respectively. The predicted amino acid (aa) sequence homologies
      revealed that gene 3b and 5b were more conserved than 3a, 3c and 5a. Each
      individual gene of CU-T2 strain (with the exception of the RNA polymerase gene)
      had a different level of homology with the homologous gene of other strains,
      suggesting that the evolution of IBV strains in general has been a complex, and
      as yet, poorly understood process.

PMID- 9168127
TI  - Identification of a large motility operon in Borrelia burgdorferi by semi-random
      PCR chromosome walking.
AB  - Motility has been implicated in the invasive process of Borrelia burgdorferi
      (Bb), the etiologic agent of Lyme disease. To identify Bb motility related genes,
      we used a method termed 'semi-random PCR chromosome walking' (SRPCW) to walk
      through a large motility gene cluster. The major advantage of this approach over
      other PCR walking methods is that it employs a secondary PCR amplification of
      cloned fragments which can be readily sequenced and analyzed. Starting with a
      primer specific to flgE, we identified and sequenced 14 open reading frames
      (ORFs) spanning 11 kb downstream of the flgE gene. The genes identified include
      flbD, motA, motB, fliL, fliM, fliN, fliZ, fliP, fliQ, fliR, flhB, flhA, flhF and
      flbE. Twelve of the deduced proteins shared extensive homology with flagellar
      proteins from other bacteria. The gene products and order of genes within this
      cluster are most similar to those of Treponema pallidum (Tp) and Bacillus
      subtilis (Bs). One of the unique genes identified, flbD, demonstrated homology to
      an ORF from the same operon of Tp. Another ORF, flbE, showed similarity to genes
      from both Tp and Bs. RT-PCR and primer extension analysis revealed that this gene
      cluster is transcribed as a single unit indicating that it is part of a large
      motility operon spanning more than 21 kb. Antisera to Escherichia coli and
      Salmonella typhimurium FliN, FliM, FlhB and FlhA reacted with proteins of the
      predicted molecular weights in cell lysates of Bb. The results suggest that the
      flagellar system is highly conserved in evolution and thus underscore the
      importance of motility in bacterial survival and pathogenesis.

PMID- 9168128
TI  - The rpoH gene encoding sigma 32 homolog of Vibrio cholerae.
AB  - The Vibrio cholerae rpoH gene coding for the heat-shock sigma factor, sigma 32,
      has been cloned and shown to functionally complement Escherichia coli rpoH
      mutants. The nt sequence of the gene has been determined and the deduced aa
      sequence is more than 80% homologous to the E. coli rpoH gene product. Downstream
      of the V. cholerae rpoH gene, an unidentified dehydrogenase gene (udhA) is
      present on the opposite strand facing rpoH. The predicted secondary structure of
      the 5'-proximal region of V. cholerae rpoH mRNA is apparently different from the
      conserved secondary structures of the rpoH mRNA reported for several bacterial
      species. The 'RpoH box', a stretch of 9 aa (QRKLFFNLR) unique to sigma 32
      factors, and the 'downstream box' sequence complementary to a part of the 16S
      rRNA, have been detected.

PMID- 9168129
TI  - In vivo footprints are found in the Xenopus 63 kDa keratin gene promoter prior to
      the appearance of mRNA.
AB  - Previous work on the promoter region of the 63 kDa keratin gene demonstrated that
      in vivo footprints did not change during the transition from low-level to high
      level transcription. Reverse transcription polymerase chain reaction and in vivo
      footprinting were used to determine if these DNA-protein interactions are present
      before transcription begins. The results presented indicate that during
      development, DNA-protein interactions are present in the promoter region of the
      63 kDa keratin gene at stage 44, four days prior to the initial appearance of 63
      kDa keratin mRNA, at stage 48. Thus, the occupancy of these sites at stage 44 is
      not sufficient for transcription, but may have a role in 'poising' the keratin
      promoter for the initiation of epidermal-specific transcription. The results
      suggest that the developmental history of a gene may be important in regulating
      its temporal and spatial expression.

PMID- 9168130
TI  - Drosophila melanogaster NADPH-cytochrome P450 oxidoreductase: pronounced
      expression in antennae may be related to odorant clearance.
AB  - Insects perceive a large number of airborne chemicals as olfactory components
      mainly through the antenna. It is thought that detection of the odorants by
      specific receptors is followed by a degradative pathway that clears the olfactory
      organ from accumulating chemicals. In Drosophila, a number of P450 monooxygenases
      are involved in the metabolism of foreign chemicals [Dunkov et al. (1996)
      Cytochrome P450 gene cluster in Drosophila melanogaster, Mol. Gen. Genet. 251,
      290-297]. NADPH-cytochrome P450 oxidoreductases serve to transfer reducing
      equivalents to P450 monooxygenases. We isolated cDNA and genomic clones coding
      for a Drosophila NADPH cytochrome P450 oxidoreductase (CPR). The largest cDNA of
      2471 nucleotides in length contained an open reading frame of 693 amino acids
      that includes the putative CPR sequence. CPR is a single copy gene as shown by
      genomic Southern hybridisation and maps to the cytogenetic map position 26C on
      the second chromosome. Comparison of genomic and cDNA CPR sequences revealed a
      gene structure that is split into at least six exons. The CPR protein sequence is
      almost identical with that of house fly and remarkably conserved when compared to
      vertebrates and yeast. RNA expression is high in embryos and antennae as compared
      to adult heads, adult bodies and larvae. High expression in antennae may reflect
      the putative function in olfactory clearance.

PMID- 9168131
TI  - Expression of Tetrahymena snRNA gene variants including a U1 gene with mutations
      in the 5' splice site recognition sequence.
AB  - The expression of U1, U2 and U5 snRNA gene variants has been studied under
      different physiological states of Tetrahymena. Variants of all three snRNA genes
      are expressed. Among the snRNAs detected is U1-3, a variant with 66 mutations
      compared to the normal U1 snRNA. Three of these mutations affect the 5' splice
      site recognition sequence. The U1-3 snRNA is present in a few hundred copies per
      cell. The expression of Tetrahymena snRNA genes is independent of the
      physiological state of the cell.

PMID- 9168132
TI  - Identification of critical CpG sites for repression of L1 transcription by DNA
      methylation.
AB  - L1 (LINE-1) is an interspersed non-LTR retrotransposon and several genetic
      defects caused by L1 transposition have been reported. L1 is thus considered as a
      potential mutagen. However, this potentially hazardous insertional event seems to
      be rare in spite of the presence of 3000 or more L1 elements of full or nearly
      full length in the human genome. Thus there must exist a mechanism(s) for
      repressing the expression of most, if not all, L1 elements. Some studies
      suggested that methylation plays a major role in the repression of L1 expression.
      However, no direct evidence has been presented and further study is required to
      draw a conclusion. We thus studied the effect of methylation on L1 transcription
      in vivo and in vitro. Transfection of plasmid which contained a L1 promoter
      linked to cat gene into HeLa cells showed that methylation did repress the L1
      promoter activity. In vitro transcription studies using mutagenized templates
      indicated that methylation of the first seven CpGs in L1 promoter, particularly
      four CpGs at +52, +58, +61 and +70 was essential for the inhibition. These
      results suggest that there exists a mechanism to regulate the L1 transcription
      through the region-specific methylation.

PMID- 9168133
TI  - Gene organization of human NOTCH4 and (CTG)n polymorphism in this human
      counterpart gene of mouse proto-oncogene Int3.
AB  - The cDNA and genomic clones for the human counterpart of the mouse mammary tumor
      gene Int3 were isolated and sequenced. We designated this human major
      histocompatibility complex (MHC) class III gene as NOTCH4, since very recently,
      by sequencing cDNA clones, the complete form of the mouse proto-oncogene Int3 has
      been clarified and named Notch4. The present human NOTCH4 sequence is the first
      example of the genomic sequence for the extracellular portion of the mammalian
      Notch4, and by comparing it with the mouse Notch4 cDNA sequence, the exon/intron
      organization was clarified. The comparison of the predicted amino acid sequence
      of human NOTCH4 with those of other Notch homologues of a wide range of species
      revealed four subfamilies for mammalian Notch. In the protein coding region of
      human NOTCH4, we found (CTG)n repeats showing a variable number tandem repeat
      (VNTR) polymorphism for different human leukocyte antigen (HLA) haplotypes. Ten
      genes mapped on 6p21.3, including NOTCH4, were found to have counterparts
      structurally and functionally similar to those mostly mapped on 9q33-q34,
      indicating segmental chromosome duplication during the course of evolution.
      Similarity of genes on chromosomes 1, 6, 9 and 19 was also discussed.

PMID- 9168134
TI  - Analysis of genes for human snRNP Sm-D1 protein and identification of the
      promoter sequence which shows segmental homology to the promoters of Sm-E and U1
      snRNA genes.
AB  - The Sm core proteins of U1, U2, U4/U6 and U5 snRNPs include B(B1), B'(B2), N(B3),
      D1, D2, D3, E, F and G polypeptides. We have isolated genomic clones encoding the
      Sm-D1 protein using the Sm-D1 cDNA as probe. Southern blotting and DNA sequencing
      analysis of these clones revealed the presence of an Sm-D1 multigene family in
      the human genome. Three gene members have been identified. Two of the genes are
      without introns and contain mutations compared to the cDNA sequence. They appear
      to be processed pseudogenes. The third gene, termed SNRPD1, shares 100% identity
      to the cDNA sequence including both 5'- and 3'-untranslated regions (UTR); it
      contains three introns. Analysis of the 5'-flanking region of the SNRPD1 gene
      revealed promoter activity, suggesting this is the functional gene that encodes
      the Sm-D1 protein. The promoter activity was localized in a 0.38 kb PstI fragment
      using CAT reporter gene fusion assays. Addition of an SV40 enhancer element did
      not enhance the transcription directed by that fragment. Sequence comparison of
      the 0.38 kb promoter sequence with the promoters of the Sm-E gene and U1 snRNA
      genes revealed several homologous motifs, suggesting that genes encoding the
      snRNP components may be coordinately regulated.

PMID- 9168135
TI  - Cloning and sequence analysis of zooA, a Streptococcus zooepidemicus gene
      encoding a bacteriocin-like inhibitory substance having a domain structure
      similar to that of lysostaphin.
AB  - The nucleotide sequence has been determined for zooA, a gene encoding the
      bacteriocin-like inhibitory substance zoocin A in Streptococcus zooepidemicus
      strain 4881. The zooA gene product corresponds to the 285-amino acid (aa) zoocin
      A pre-peptide from which a leader sequence is cleaved to form the 262-aa
      biologically active molecule of estimated molecular mass 27,877 Da. Expression of
      zooA in a Gram-negative host was shown by the extracellular release from
      Escherichia coli, containing cloned zooA, of a biologically active peptide having
      an identical range of anti-bacterial activity to that of zoocin A, purified from
      S. zooepidemicus strain 4881. Data base searches revealed sequences having
      homologies with known muralytic proteins produced by both Gram-positive and Gram
      negative bacteria and indicate a 'mix and match' blending of domain-type
      structures, the C-terminal putative receptor-recognition region of the molecule
      being joined by a threonine-proline-rich linker to an N-terminal putative
      catalytic region having homology with several known endopeptidases, including
      lysostaphin.

PMID- 9168136
TI  - Increased chromokinesin immunoreactivity in retinoblastoma cells.
AB  - chromokinesin is a developmentally down-regulated gene with specific expression
      in proliferating cells during embryonic chick development. It encodes a DNA
      binding motor protein localized along the chromosome arm during mitosis,
      suggesting that the protein may be a component of the long-observed, yet poorly
      understood 'ejection force' hypothesized to be involved in controlling the
      direction and speed of chromosome movement. We have isolated human chromokinesin;
      with affinity-purified antibodies we demonstrated immunocytochemically that
      Chromokinesin was present at a much higher level in cultured retinoblastoma cells
      than in primary cultures of human dermal fibroblasts. The increase in
      immunoreactivity was particularly prominent in interphase cells, whereas in
      primary cultures of fibroblasts immunopositive cells were predominantly M-phase
      cells. These observations imply a deregulation of chromokinesin in retinoblastoma
      cells. Data presented here may be useful in designing strategies to modulate
      chromosome movement and cell proliferation with either antisense oligonucleotides
      or specific antibodies, and hence may set the stage for further investigations of
      the involvement of chromosome motor molecules in mitosis under normal and
      pathological conditions.

PMID- 9168138
TI  - Cloning and characterization of a novel gene, WS-3, in human chromosome 8p11-p12.
AB  - A novel human gene referred to as the WS-3 gene, in the short arm of human
      chromosome 8, was cloned by a combination of exon trapping, thermal asymmetric
      interlaced-PCR (TAIL-PCR) and the Marathon-Ready cDNA amplification method. The
      gene consists of 7 exons separated by 6 introns, and is at the telomere side of
      the STS marker, D8S1055. The full-length WS-3 gene contains 1052 nucleotides and
      codes for a protein of 190 amino acids with a calculated mol. wt. of 20,747.
      Southern blot experiments showed that the WS-3 gene exists as a single copy in
      the human genome. A protein encoded by the WS-3 gene has an R-G-D (Arg-Gly-Asp)
      motif in the N-terminal region, which seems to confer adhesive properties to
      macromolecular proteins like fibronectin. Although WS-3 is a small gene with
      unknown biological function, its ubiquitous expression in various tissues and
      organs suggests that the encoded protein is one of the essential components of
      all organs and tissues.

PMID- 9168137
TI  - Myelin and lymphocyte protein (MAL/MVP17/VIP17) and plasmolipin are members of an
      extended gene family.
AB  - An increasing number of four-transmembrane proteins has been found to be
      associated with CNS and PNS myelin. Some of these proteins play crucial roles in
      the development and maintenance of the nervous system. In the CNS, proteolipid
      protein (PLP) is mutated in the myelin disorder Pelizaeus-Merzbacher disease and
      in spastic paraplegia, while in the PNS, peripheral myelin protein 22 (PMP22) and
      connexin32 (C x 32) are culprit genes in the most frequent forms of hereditary
      peripheral neuropathies. Myelin and lymphocyte protein (MAL; also called MVP17 or
      VIP17) and plasmolipin are additional tetraspan proteins that are highly
      expressed by myelinating glial cells. However, little is known about the role of
      these proteins in the nervous system. As a prerequisite for functional genetic
      approaches in the mouse, we have isolated and characterized a mouse MAL cDNA and
      the corresponding structural MAL gene. Computer-aided analysis and database
      searches revealed that MAL belongs to a larger gene family which also includes
      plasmolipin, BENE and the expressed sequence tag (EST) H09290. While the overall
      amino acid sequence identities between mouse MAL and the related proteins are
      relatively low (29-37%), the conserved motif -[Q/Y-G-W-V-M-F/Y-V]- which is found
      at the junction of the first extracellular loop and the second membrane
      associated domain serves as a fingerprint for the MAL protein family. Expression
      analysis of the members of the MAL gene family indicates widespread expression in
      various tissues, suggesting a common role of these proteins in cell biology.

PMID- 9168139
TI  - Recharacterization of the start sites for the major human transforming growth
      factor-beta 1 mRNA.
AB  - The start sites for the major human TGF-beta 1 transcripts have been reexamined.
      A comparison of ribonuclease and S1 nuclease protection analyses on native TGF
      beta 1 mRNA and in vitro transcribed human TGF-beta 1 transcripts of defined
      sizes places the most 5' start site for the native TGF-beta 1 message approx. 50
      nucleotides upstream from the previously published start site at base +1.
      Furthermore, the same techniques indicate that the apparent downstream start site
      at base +271 is an artefact due to the presence of an A + T-rich island in the
      middle of an otherwise highly G + C-rich sequence. This is not apparent if S1
      nuclease protection is used alone, which emphasizes the importance of using the
      two techniques in combination for this type of analysis. Thus the major 2.5 kb
      TGF-beta 1 band seen on Northern blots comprises only mRNA transcribed from the
      more upstream of the two previously characterized promoters. This has important
      implications both for the transcriptional and translational regulation of this
      growth factor.

PMID- 9168140
TI  - Cytoplasmic delivery of calcein mediated by liposomes modified with a pH
      sensitive poly(ethylene glycol) derivative.
AB  - Previously, as a new type of pH-sensitive liposome, we prepared egg yolk
      phosphatidylcholine (EYPC) liposomes bearing succinylated poly(glycidol), that is
      a poly(ethylene glycol) derivative having carboxyl groups, and showed that fusion
      ability of the liposomes increases under weakly acidic and acidic conditions
      (Kono, K., Zenitani, K. and Takagishi, T. (1994) Biochim. Biophys. Acta 1193, 1
      9). In this study, we examined intracellular delivery of a water-soluble
      molecule, calcein, mediated by the succinylated poly(glycidol)-modified
      liposomes. When CV-1 cells, an established line of African green monkey kidney
      cells, were incubated with bare EYPC liposomes containing calcein at 37 degrees
      C, only weak and vesicular fluorescence of calcein was observed by using a
      fluorescence microscope. In contrast, the cells treated with the polymer-modified
      liposomes containing calcein displayed more intensive and diffuse fluorescence,
      indicating that calcein was transferred into the cytoplasm. Uptake of the polymer
      modified liposomes by the cells was shown to decrease slightly as amount of the
      polymer fixed on the liposome increases. However, the fluorescence of calcein
      observed in the liposome-treated cell was, on the contrary, enhanced as amount of
      the polymer fixed on the liposome increases, indicating that the liposome
      modified with a higher amount of the polymer transfers its content into cytoplasm
      more efficiently after internalization into the cell. Fusion assay by resonance
      energy transfer using N-(7-nitrobenz-2-oxa-1,3-diazol-4
      yl)phosphatidylethanolamine and lissamine rhodamine B
      sulfonylphosphatidylethanolamine suggested occurrence of fusion between the
      polymer-modified liposomes and endosomal and/or lysosomal membranes. Moreover,
      the liposome with a higher polymer content revealed higher percent fusion after
      internalization into the cell. These results imply that the polymer-modified
      liposomes transfer the content into the cytoplasm by fusing with the endosomal
      membrane after internalization into the cells through an endocytic pathway.

PMID- 9168141
TI  - Diffusion membrane potential in liposomes: setting by ion gradients, absolute
      calibration and monitoring of fast changes by spectral shifts of diS-C3(3)
      fluorescence maximum.
AB  - A novel fluorescent technique for direct assessment of membrane potential was
      tested on suspensions of large unilamellar vesicles (LUV). The method is based on
      monitoring shifts in the fluorescence maximum, lambda(max), of the redistribution
      dye diS-C3(3) caused by dye binding to the LUV membrane. A theory describing the
      behavior of this dye in LUV suspensions was elaborated and tested. The diffusion
      potentials across the LUV membrane were adjusted by ion gradients in the absence
      of valinomycin. When using KCl and choline chloride without valinomycin the
      potential can be set as high as -70 mV. These potentials exhibited long-term
      stability and the theory allowed to determine the upper limits of membrane
      permeabilities for Cl-, choline cations, protons and hydroxyls relative to the K+
      permeability. The absolute values of membrane potential set by ion gradients were
      calibrated using valinomycin. The monitoring of the lambda(max) shift permitted
      us to show real-time changes in membrane potential, since addition of valinomycin
      to the LUV was followed by an immediate depolarization. The setting of the
      potential and the dye re-equilibration after valinomycin addition took place
      within a second.

PMID- 9168142
TI  - Time-resolved X-ray reflectivity measurements of protein binding onto model lipid
      membranes at the air-water interface.
AB  - The energy-dispersive X-ray reflectometry and turbidity measurements are used to
      investigate the kinetics of concanavalin A binding onto the
      distearoylphosphatidylcholine/distearoylphosphatidylethanolamine-+
      ++maltobionamide (DSPC/DSPE-mal1) or
      distearoylphosphatidylcholine/distearoylphosphatidylethanolamine-+
      ++maltotetrabionamide (DSPC/mal3) mixed monolayer at the air-water interface. The
      resulting adsorbed layer of this sugar-binding protein near the membrane with one
      or three hexoses in the lipid head-group is 3.9 nm or 9.7 nm thick, respectively.
      The different thicknesses of the adsorbed layer can be correlated with the
      diverse orientations of the adsorbed proteins. These lay flat on the surface
      containing DSPE-mal1 and 'perpendicular' to the surface containing DSPE-mal3. The
      monolayer structure is little affected by concanavalin A binding, but the
      incorporation of sugar lipids decreases the chain tilt and the interfacial
      thickness marginally. The binding is quasi-exponential with the time constant
      between some minutes and several hours depending on the concanavalin A and
      vesicle concentrations in the bulk. The experimental resolution of the time
      resolved measurements made with the laboratory-based instrument is 15 min and the
      spatial resolution is between 0.05 nm and 0.5 nm, depending on the electron
      contrast. It is estimated that the high-brilliance synchrotron X-ray source
      combined with the detection method outlined in this work, could permit the
      kinetic measurements on the time-scale of < 1 minute.

PMID- 9168143
TI  - A voltage- and K+-dependent K+ channel from a membrane fraction enriched in
      contractile vacuole of Dictyostelium discoideum.
AB  - We obtained a membrane fraction enriched in the contractile vacuole by aqueous
      polymer two-phase partitioning and its channel activities were analysed by
      incorporating it into artificial planar lipid bilayers. In asymmetrical KCl
      solutions (cis, 300 mM/100 mM, trans), we observed single-channel currents of a
      highly K(+)-selective channel with slope conductance of 102 pS and reversal
      potential of -20.4 mV, which corresponded to PK+/PCl- = 7. They showed bursts
      separated by infrequent quiescent periods. At 0 mV the mean open time was 2.0 ms.
      Among monovalent cations, Na+ and Li+ were impermeable, whereas Rb+ showed
      permeability equivalent to that of K+, although the unitary conductance was
      apparently reduced when the current flowed from the Rb+ containing side,
      suggesting that Rb+ is a permeant blocking ion. The open probability within
      bursts remained constant at approx.0.6 as long as the holding potential was
      positive on the cis side with respect to the trans side, but it decreased to 0 at
      negative potential. This channel was blocked by submillimolar concentrations of
      quinine and 30 mM TEA+. The open probability-voltage relationship showed a
      striking dependency on the KCl concentration on either side. This channel may
      play a role in water transport in this organelle.

PMID- 9168144
TI  - Interaction of local anesthetic heptacaine homologs with phosphatidylcholine
      bilayers: spin label ESR study.
AB  - Local anesthetic monohydrochlorides of [2-(alkoxy)phenyl]-2-(1-piperidinyl)ethyl
      esters of carbamic acid (CnA, n = 2, 3, 4, 6, 8, 10, 12 is the number of carbon
      atoms in the alkyloxy substituent) increase the probability of formation of
      gauche isomers p(g) and decrease the effective energy difference between gauche
      and trans conformation E(g) in egg yolk phosphatidylcholine (EYPC) acyl chains,
      as determined by electron spin resonance spectroscopy using
      dipalmitoylphosphatidylcholines labeled with the paramagnetic
      dimethyloxazolidinyl group on the 12-th or 16-th carbon atoms of their sn-2 acyl
      chain, and oriented EYPC bilayers hydrated at 81% relative water vapour pressure.
      CnAs also increase the hydration of EYPC in non-oriented bilayers at the same
      relative water vapour pressure. At the molar ratio of CnA:EYPC = 0.4:1, the
      maximum effect on p(g), E(g) and hydration has been observed for intermediate
      alkyloxy chain lengths n approximately 4/6.

PMID- 9168145
TI  - Comparison of ouabain-sensitive and -insensitive Na/K pumps in HEK293 cells.
AB  - The Na/K pump current I(p) of single HEK293 cells either untransfected
      (endogenous I(p)) or transfected with the alpha1 subunit of the rat Na/K pump
      (exogenous I(p)) was investigated in Na-containing solution by means of whole
      cell recording at 30 degrees C. The endogenous I(p) was irreversibly blocked by
      10(-4) M ouabain or 2 x 10(-4) M dihydro-ouabain (DHO). Its density amounted to
      0.33 pA pF(-1) at 0 mV and 5.4 mM K(o). It was half maximally activated at 1.5 mM
      K(o) and increased linearly with depolarization over the entire voltage range
      studied (-80 to +60 mV). In contrast, HEK293 cells stably transfected with cDNA
      for the cardiac glycoside-resistant alpha1 subunit of the rat Na/K pump showed an
      I(p) in the presence of 10(-4) M ouabain and 2 x 10(-4) M DHO, respectively. This
      exogenous I(p) was reversibly blocked by 10(-2) M ouabain. Half maximal
      activation of the exogenous I(p) occurred at 1.7 mM K(o). Its amplitude increased
      linearly with depolarization at negative voltages but remained almost constant at
      positive membrane potentials. Comparison with the I(p) of isolated rat cardiac
      ventricular myocytes strongly suggests that the exogenous I(p) in HEK293 cells is
      generated by the alpha1 subunit of the rat Na/K pump since it displays identical
      properties. Therefore, HEK293 cells represent an expression system well suited
      for the electrophysiological analysis of recombinant, cardiac glycoside-resistant
      Na/K pumps by means of whole-cell recording.

PMID- 9168146
TI  - Role of the Gln/Glu residues of trichocellins A-II/B-II in ion-channel formation
      in lipid membranes and catecholamine secretion from chromaffin cells.
AB  - Trichocellins (TC) A-II and B-II, 20-residue peptaibols isolated from conidia of
      the fungus Trichoderma viride, have the same sequence except for the residue at
      position 18. Both TCs were found to form voltage-dependent ion-channels in
      bilayer lipid membranes (BLM) and to induce catecholamine secretion from bovine
      adrenal chromaffin cells through Ca2+ influx. TC-A-II (Gln18, neutral) was more
      effective than TC-B-II (Glu18, charged) for macroscopic current induction in BLMs
      and for catecholamine secretion from chromaffin cells, suggesting that Glu18 is
      unfavorable for the ion-channel formation in BLMs and chromaffin cell membranes.
      Nevertheless, single-channel recordings indicated that TC-B-II forms larger pores
      with longer open lifetimes than those of TC-A-II. This indicates that the
      negatively charged carboxyl group of Glu at position 18 stabilizes larger pores.
      The effects of the negative charge of Glu18 on the activities were confirmed by
      the use of a TC-B-II analog containing the methyl ester of Glu18.

PMID- 9168147
TI  - Relationship between specific binding of 125I-omega-conotoxin GVIA and GTP
      binding protein: effects of the GTP analogues, mastoparan and A1F4-.
AB  - We investigated whether the specific binding or labeling of 125I-omega-CgTX on
      crude membranes from chick whole brain was affected when endogenous GTP binding
      protein (G protein) was activated by GTP analogues, mastoparan (MP) and aluminum
      fluoride (AIF4-; AICl3 + NaF). Both GTPgammaS and Gpp(NH)p attenuated the
      inhibitory effect of selective N-type Ca channel inhibitors such as
      aminoglycoside antibiotics (AGs) or dynorphine (1-13)(Dyn) on specific 125I-omega
      CgTX binding in a dose-dependent manner. On the other hand, the inhibitory
      effects of the divalent metal cations Cd2+, Co2+, Mg2+ and Mn2- on such binding
      were not attenuated by GTPgammaS. MP and AIF4- also attenuated the inhibitory
      effect of Neo on this binding similar to GTPgammaS. The attenuating effect of MP
      was enhanced by the presence of Mg2+ in a dose-dependent manner. However, GTP
      analogues, MP and AIF4-, did not affect binding or labeling without AGs or Dyn.
      GTPgammaS, MP and AIF4- also attenuated the specific labeling of a 215-kDa band
      in crude membranes with 125I-omega-CgTX using the cross-linker DSS (non-reduced
      condition) in the presence of Neo. These results indicate that there are direct
      or indirect relationships between N-type Ca channels and G proteins via binding
      sites for AGs or MP.

PMID- 9168149
TI  - Alamethicin channels - modelling via restrained molecular dynamics simulations.
AB  - Alamethicin channels have been modelled as approximately parallel bundles of
      transbilayer helices containing between N = 4 and 8 helices per bundle. Initial
      models were generated by in vacuo restrained molecular dynamics (MD) simulations,
      and were refined by 60 ps MD simulations with water molecules present within and
      at the mouths of the central pore. The helix bundles were stabilized by networks
      of H-bonds between intra-pore water molecules and Gln-7 side-chains. Channel
      conductances were predicted on the basis of pore radius profiles, and suggested
      that the N = 4 bundle formed an occluded pore, whereas pores with N > or = 5
      helices per bundle were open. Continuum electrostatics calculations suggested
      that the N = 6 pore is cation-selective, whereas pores with N > or = 7 helices
      per bundle were predicted to be somewhat less ion-selective.

PMID- 9168148
TI  - Cytoskeleton-membrane connections in the human erythrocyte membrane: band 4.1
      binds to tetrameric band 3 protein.
AB  - Band 4.1 provides, besides ankyrin, the main linkage between the erythrocyte
      membrane and its cytoskeleton. Its predominant binding sites in the membrane are
      located on the glycophorins. However, the cytoplasmic domain of band 3 can also
      bind band 4.1. We have studied which of the different band 3 oligomers observed
      (monomers, dimers, tetramers) can act as band 4.1 binding sites, by equilibrium
      sedimentation experiments on mixtures of purified band 3 and dye-labelled band
      4.1 in solutions of a nonionic detergent. At low molar ratios of band 4.1 and
      band 3, the sedimentation equilibrium distributions obtained could all be
      perfectly fitted assuming that only two dye-labelled particles were present:
      uncomplexed band 4.1 and a complex formed between one band 4.1 molecule and one
      band 3 tetramer. The presence of small amounts of complexes containing band 3
      monomers or dimers could not be completely ruled out but is unlikely. On the
      other hand, stabilized band 3 dimers effectively bound band 4.1. At higher molar
      band 4.1/band 3 ratio, the band 3 tetramer apparently could bind up to at least
      four band 4.1 molecules. The band 4.1/band 3 tetramer complex was found to be
      unstable. The results described, together with those reported previously, point
      at a prominent role of tetrameric band 3 in ligand binding.

PMID- 9168150
TI  - Methyl mercury interactions with phospholipid membranes as reported by
      fluorescence, 31P and 199Hg NMR.
AB  - Methylmercury (CH3Hg(II)) interactions with multilamellar vesicles of
      dimyristoyl(DM)- and dipalmitoyl(DP)-phosphatidylcholine (PC), -phosphatidic acid
      (PA), -phosphatidylglycerol (PG), -phosphatidylserine (PS) and 
      phosphatidylethanolamine (PE) have been investigated from the metal viewpoint by
      solution 199Hg-NMR and from the membrane side by diphenylhexatriene fluorescence
      polarization and solid state 31P-NMR. Results can be summarized as follows: (1)
      CH3Hg(II) strong binding to membranes results in a progressive decrease of the
      free CH3HgOH 199Hg-NMR isotropic signal and because of a slow exchange, in the
      NMR time scale, between free and bound methylmercury pools the lipid/water
      partition coefficients, K(lw), of the CH3HgOH species can be determined in the
      lamellar gel (fluid) phase. It is found: K(lw)(DMPC) approximately 2 +/- 2 (2 +/-
      2); K(lw)(DMPE) approximately 7 +/- 3 (16 +/- 3); K(lw)(DMPG) = 170 +/- 10 (110
      +/- 10); K(lw)(DMPS) = 930 +/- 50 (1250 +/- 60); K(lw)(DMPA) = 1250 +/- 60 (300
      +/- 20). CH3Hg(II) interactions with membrane phospholipids are therefore
      electrostatic in nature and the phosphate moiety is proposed as a potential
      binding site. (2) The presence of CH3HgOH stabilizes the PG gel phase and
      destabilizes that of PS. No effect is observed on PC, PA and PE thermotropism.
      (3) methylmercury promotes the formation of isotropic 31P-NMR lines with PG, PA
      and PE systems suggesting the presence of non-bilayer phases and hence membrane
      reorganization. The above effects are compared to those of inorganic mercury
      Hg(II) and discussed in the context of cell toxicity.

PMID- 9168151
TI  - Na+-H+ exchange and intracellular pH regulation in colonocytes from the chick.
AB  - The involvement of Na(+)-H+ exchange in chicken colonocyte homeostasis was
      investigated. Colonocyte pH (pH(i)) was measured with 2',7'-bis(carboxyethyl)-5,6
      carboxyfluorescein (BCECF). The proton ionophore FCCP reduced basal pH(i),
      indicating that cytosolic [H+] is not at electrochemical equilibrium across the
      membrane. External Na+ removal decreased pH(i) and subsequent addition of Na+
      returns pH(i) towards its control value. The rate of pH(i) recovery from an acid
      load was Na(+)-dependent (K(m) for Na+, 24 mM) and inhibited by EIPA (IC50, 0.18
      microM). The initial rate of Na(+)-dependent cell alkalization increased as the
      pH(i) decreased from 7.2 to 6.6 (Hill coefficient, 1.88). Radioisotope flux
      studies revealed that an outwardly directed proton gradient transiently
      stimulated Na+ uptake into BBMV isolated from the chick colon. EIPA and amiloride
      inhibited pH gradient-driven Na+ uptake (IC50 of 4 microM and 32 microM,
      respectively). The K(m) for Na+ of pH gradient-driven Na+ uptake was 6.8 mM. The
      Hill coefficient of the relationship between the initial rate of pH-driven Na+
      uptake and the intravesicular pH was 0.70. It is concluded that a Na(+)-H+
      exchanger is involved in pH(i) homeostasis in chicken colonocytes and that these
      cells possess at least two types of Na(+)-H+ antiporters with different
      sensitivity to EIPA and different kinetic parameters.

PMID- 9168152
TI  - Effects of pressure and local anesthetic tetracaine on
      dipalmitoylphosphatidylcholine bilayers.
AB  - The temperature-pressure phase diagram of dipalmitoylphosphatidylcholine (DPPC)
      multilamellar vesicles was constructed in the presence of a local anesthetic
      tetracaine hydrochloride (TC-HCl). The phase-transition temperatures under
      various pressures were determined by the method of high-pressure light
      transmission. The temperature of the main transition from the ripple gel
      (P'(beta)) to the liquid crystal (L(alpha)) phase was depressed by the addition
      of TC-HCl and elevated by application of pressure up to 150 MPa. The temperature
      of the pretransition from the lamellar gel (L'(beta)) to the P'(beta) phase was
      also depressed by the addition of TC-HCl below ca. 10.0 mmol kg(-1) and elevated
      by the pressure below ca. 50 MPa. Therefore, pressure-anesthetic antagonism for
      both phase-transitions was confirmed. The pressure-induced interdigitated gel
      (L(beta)I) phase has been observed under high pressure above 100 MPa in the
      absence of TC-HCl. The L(beta)I phase is known to be induced also by a variety of
      small amphiphilic molecules such as ethanol, benzyl alcohol and TC-HCl. In the
      presence of TC-HCl ranging in concentration up to 20.0 mmol kg(-1), the L(beta)I
      phase instead of the P'(beta) phase appeared at higher pressure. Present results
      revealed that pressure facilitates, rather than antagonizes, the effect of TC-HCl
      on the occurrence of interdigitated gel phase. Furthermore, two regions of two
      phase coexistence were observed under high pressure in the presence of TC-HCl.
      One is probably a region of coexisting L(beta)I and L(alpha) phase, which was
      found between L(beta)I and L(alpha) phases under various pressures. The other is
      probably a region of coexisting L'(beta) and L(beta)I phase, which was observed
      in the presence of TC-HCl up to 10.0 mmol kg(-1) at the pressure above 40 MPa and
      at the temperature below ca. 35 degrees C.

PMID- 9168153
TI  - Staphylococcal alpha-toxin: the role of the N-terminus in formation of the
      heptameric pore -- a fluorescence study.
AB  - Staphylococcus aureus alpha-toxin forms heptameric pores on eukaryotic cell
      membranes. Assembly of the heptamer precedes formation of the transmembrane pore.
      The latter event depends on a conformational change that drives a centrally
      located stretch of 15 amino acid residues into the lipid bilayer. A second region
      of the molecule that has been implicated in the pre-pore to pore transition is
      the far N-terminus. Here, we used fluorescently labeled single cysteine
      replacement mutants to analyze the functional role of the far N-terminus of alpha
      toxin. Pyrene attached to mutants S3C, I5C and 17C forms excimers within the
      toxin pore complex. This indicates that the distance of adjacent N-termini is
      less than 10-12 Angstrom. By labeling with the polarity-sensitive fluorophore
      acrylodan, pore formation is shown to cause distinct environmental changes in the
      N-terminus. Removal of membrane lipids from the labeled heptamers has no effect
      upon the acrylodan spectrum, indicating lack of direct contact of the N-terminus
      with the target membrane. The environmental alterations to the N-terminus are
      thus due to altered protein structure only. Both acrylodan emission shifts and
      pyrene excimers were shown to be absent in toxin heptamers that were arrested at
      the pre-pore stage. Therefore, while not being directly involved in membrane
      penetration, the N-termini of the alpha-toxin heptamer subunits move into
      immediate mutual proximity concomitantly with transmembrane pore formation.

PMID- 9168154
TI  - Regulation of phospholipase C delta1 by sphingosine.
AB  - Sphingosine, which is on the pathway of sphingomyelin degradation, activates
      phospholipase C (PLC) delta1 moderately. In the liposome assay effect of
      sphingosine on PLC delta1 activity depends on KCl concentration. Stimulation of
      PLC delta1 by sphingosine increased as the KCl concentration is increased from 0
      to 100 mM, and then diminished with the increasing KCl. In the liposome assay
      sphingosine diminishes inhibition of PLC delta1 by sphingomyelin. To determine
      the domain of PLC delta1 which interacts with sphingosine active proteolytic
      fragments of PLC delta1 were generated by trypsin digestion of the native enzyme.
      Sphingosine affects the activity of PLC delta1 fragment which lacked the amino
      terminal domain (first 60 amino acids) but not the active fragment that has
      cleaved the domain spanning the X and Y region of PLC delta1. These observations
      indicate that for interaction of sphingosine with PLC delta1 intact domain that
      span regions of conservation, designated as X and Y is necessary. When the
      activity of PLC delta1 was assayed with PIP2 in the erythrocyte membrane as
      substrate, sphingosine strongly inhibited PLC delta1. The other homolog of
      sphingosine 4-hydroxysphinganine (phytosphingosine) inhibited PLC delta1 to much
      lesser extent. The activity of PLC delta1 was inhibited by 68% and 22% in the
      presence of 20 microM sphingosine and phytosphingosine, respectively. This
      inhibition was completely abolished by deoxycholate at a concentration of 1.5 mM.
      These observations suggest that sphingosine may regulate activity of PLC delta1
      in the cell.

PMID- 9168155
TI  - A liposome-based model system for the simulation of lectin-induced cell adhesion.
AB  - A parallel plate flow chamber with defined wall shear rates was developed in
      order to study and simulate cellular adhesion to biological membranes as mediated
      by lectin/carbohydrate interactions. Planar bilayers containing clustered areas
      of various long-chain alkyl mannosides as carbohydrate ligands and supported on
      transparent materials were used as model membranes. Their interaction with
      liposomes bearing Concanavalin A as model cells was observed fluorimetrically by
      confocal laser scanning microscopy. The use of supported membranes made it
      possible to study the dependence of adhesion upon different physicochemical
      parameters of membranes. The liposomes of this model were able to simulate the
      lectin-mediated adhesion of cells in a shear flow. Once specific receptor
      mediated adhesion had taken place, liposomes tended to attach irreversibly to the
      membrane. This could be avoided by employing lipid compositions which represent a
      special balance between charged and polyethylene glycol-coupled lipids. This is
      discussed in term of the interplay between the various attractive and repulsive
      forces at membrane surfaces. The dependence of liposome adhesion upon the shear
      rate could be detected. These results were used to evaluate binding forces
      between lectin-bearing liposomes and ligand-containing planar bilayers.

PMID- 9168156
TI  - Adaptive regulation of taurine and beta-alanine uptake in a human kidney cell
      line from the proximal tubule.
AB  - 1. The underlying mechanisms involved in the adaptive regulation of beta-amino
      acid uptake in the human proximal tubule were examined by use of an immortalized
      human embryonic kidney epithelial cell line (IHKE). 2. The results indicated that
      the adaptive response to maintain whole-body taurine homeostasis occurs
      predominantly via changes in the activity of the high-affinity taurine transport
      system by alterations in the uptake capacity and with an unaffected half
      saturation constant. An adaptive response was not observed for the structurally
      related beta-alanine. 3. Only colchicine, which interferes with microtubule
      organization, was capable of blocking the response to alterations of taurine in
      cell medium, whereas inhibition of protein and nucleic acid synthesis by
      cycloheximide and actinomycin D, respectively, did not change the adaptive
      pattern. 4. Phorbol 12-myristate 13-acetate (PMA), mimicking the effects of
      diacylglycerol, induced inhibition of both beta-alanine and taurine uptake. By
      contrast, the Ca2(+)-ionophore A23187, mimicking the effects of IP3, only
      stimulated the uptake of taurine but not the influx of beta-alanine. However, the
      effect of PMA down-regulation and A23187 up-regulation was rapid and short-lived
      in contrast to the adaptive response, suggesting that the inositol phospholipid
      pathway involving diacetylglycerol and IP3 is less likely to be linked directly
      to the adaptive regulation, but rather plays a role in short-term regulation.

PMID- 9168157
TI  - Specific interaction between tetrandrine and Quillaja saponins in promoting
      permeabilization of plasma membrane in human leukemic HL-60 cells.
AB  - Spontaneous Ni2+ entry (leak), measured as fluorescence quench in fura-2-loaded
      HL-60 cells at the excitation wavelength of 360 nm, was strongly inhibited by
      tetrandrine (TET, 100 microM), a Ca2+ antagonist of Chinese herbal origin.
      Exposure of the cells for 5 min to saponins from Quillaja saponaria (QS, 30
      microg/ml), surfactants well known to permeabilize the plasma membrane by
      complexing with cholesterol, promoted Ni2+ entry without causing fura-2 leak-out.
      Unexpectedly, TET caused an immediate (within 2.5 min) augmentation of QS
      promoted Ni2+ entry; and a 5-min treatment with both TET and QS resulted not only
      in an enhanced Ni2+ entry, but also a fura-2 leak-out. Ginseng saponins (100
      microg/ml) alone or together with TET did not cause such a permeabilization.
      Permeabilization induced by 1-3 microM digitonin, another cholesterol-complexing
      glycoside, could not be enhanced by TET. TET did not affect permeabilization
      induced by Triton X-100 (0.01%), a detergent which non-specifically disrupts the
      hydrophobic interaction at the plasma membrane. TET also did not enhance Ni2+
      entry triggered by ionomycin (0.35 microM) or SK&F 96365 (20 microM). Further, it
      did not augment Ni2+ entry when the plasma membrane fluidity was modulated by
      changes of temperature (27-47 degrees C) or treatment with 5% ethanol. This QS
      promoted Ni2+ entry could not be amplified by other lipophilic Ca2+ antagonists,
      such as diltiazem (100 microM) and verapamil (100 microM). The results hence
      indicate that TET enhanced Ni2+ entry (or permeabilization) elicited by QS
      treatment, but not other perturbations of the plasma membrane. We suggest that
      pore formation at the plasma membrane, a consequence of QS-cholesterol
      interaction, can be specifically enhanced by TET. Also, a comparative study of
      the effects of TET and its very close analogues, hernandezine and berbamine,
      reveals that the methoxyl group at the R2 position of TET appears to be crucial
      in enhancing QS-promoted Ni2+ entry.

PMID- 9168158
TI  - In vitro study of passive nitrate transport by native and reconstituted plasma
      membrane vesicles from corn root cells.
AB  - Proteins from phase-partitioned corn root plasma membrane were reconstituted into
      soybean lipids/egg PC (8:2, w:w) using deoxycholate and rapid gel filtration to
      eliminate the detergent. All (H+)ATPase molecules were inside-out reinserted and
      the initial activity was totally recovered in an homogeneous vesicle preparation.
      In addition, membrane tightness greatly increased, as shown by the size and
      stability of the response of the fluorescent membrane potential probe (oxonol VI)
      to an imposed K+ diffusion gradient. Consequently, the H(+)-pumping activity of
      the (H+)ATPase, monitored with the fluorescent pH probe (ACMA), increased 20-fold
      after reconstitution. A protein-mediated passive transport of nitrate was first
      demonstrated by the ability of NO3- to electrically short-circuit the (H+)ATPase
      in plasma membrane vesicles and not in liposomes containing only the purified
      enzyme. The passive transport was saturable (K(m) approximately 5 mM),
      thermolabile, inhibited by the arginine reagent phenylglyoxal, and selective (NO3
      > I- approximately ClO3- approximately Br- > Cl- approximately NO2- >
      Iminodiacetate approximately SO4(2-)). Passive NO3- transport was also
      determined, independently of the (H+)ATPase, from the NO3(-)-dependent
      augmentation of the dissipation rate of imposed diffusion potentials. This second
      transport assay gave similar K(m) for NO3- and should be suitable to continue the
      functional and biochemical characterization of the NO3- transport system.

PMID- 9168159
TI  - Cell death and birth in multiple sclerosis brain.
AB  - The hallmark of the brain pathology in multiple sclerosis is the white matter
      plaque, characterized by myelin destruction and oligodendrocyte loss. To examine
      the role that cell death plays in the development of MS lesions, we used the in
      situ TUNEL technique, a method that sensitively detects DNA fragmentation
      associated with death at the single cell level. We found that patchy areas within
      acute MS lesions have massive numbers of inflammatory and glial cells undergoing
      cell death. The punched out areas of some long-standing chronic lesions also had
      labeled glial cells showing that the attack was not a single event.
      Immunocytochemical identification of the dying cells with glial specific marker
      co-labeling showed that 14-40% were the myelin-sustaining oligodendroglial cell.
      Confocal microscopic evaluation of fluorescein-labeled TUNEL positive cells
      revealed nuclei with morphologic characteristics of apoptosis, and
      electrophoresed MS brain DNA produced a ladder characteristic of apoptotic DNA
      cleavage confirming that substantial numbers of labeled cells, but not
      necessarily all, were dying by apoptotic mechanisms rather than cell necrosis.
      Companion studies using a marker for cell proliferation on MS lesions revealed
      that unexpectedly large populations of perivascular inflammatory cells and
      parenchymal glial cells had entered the cell proliferation cycle. These findings
      establish that two opposing glial cell responses - relentless cell death and
      coincident brisk cellular proliferation - are important features of MS pathology.
      In the end, however, glial cell loss prevails, and we suspect apoptosis may be
      the critical death mechanism responsible for the depletion of myelin observed in
      this condition.

PMID- 9168160
TI  - Delayed neurite regeneration and its improvement by nerve growth factor (NGF) in
      dorsal root ganglia from MRL-lpr/lpr mice in vitro.
AB  - We studied neurite regeneration in MRL-lpr/lpr mice, a murine model of systemic
      lupus erythematosus, using a culture system to investigate the influences of
      immunological abnormalities on neurons. The regeneration of cultured dorsal root
      ganglion (DRG) neurons from MRL-lpr/lpr mice was delayed compared with control
      MRL-+/+ mice. This modification of regeneration was age-dependent. MRL-lpr/lpr
      mice older than 16 weeks of age exhibited less neurite regeneration than controls
      but those younger than 6 weeks of age showed equal regeneration. Regeneration was
      improved by adding nerve growth factor (NGF) to culture medium. Following
      immunocytochemical staining, we counted the low affinity NGF receptor p75
      positive DRG neurons in MRL mice. The percentage of p75-positive neurons in MRL
      lpr/lpr mice older than 16 weeks of age was higher than that in MRL-+/+ mice.
      These neuronal abnormalities were thought not to be directly dependent on the
      genetic defect of Fas antigen, which is related to apoptosis in MRL-lpr/lpr mice,
      but to be the result of immunological abnormalities. The present study is the
      first to demonstrate a modification of neurite regeneration by immunological
      dysfunction in autoimmune mice.

PMID- 9168161
TI  - Cellular and mitochondrial toxicity of zidovudine (AZT), didanosine (ddI) and
      zalcitabine (ddC) on cultured human muscle cells.
AB  - Zidovudine (AZT), didanosine (ddI) and zalcitabine (ddC) are the reference
      antiretroviral therapy in patients with AIDS. A toxic mitochondrial myopathy can
      be observed in patients treated with AZT, but not with ddI and ddC. All 3
      compounds can inhibit mitochondrial (mt)DNA polymerase and cause termination of
      synthesis of growing mtDNA strands and mtDNA depletion. The propensity to injure
      particular target tissues is unexplained. In our work, cultured muscle cells
      prepared from human muscle biopsies, were exposed to various concentrations of
      AZT (4-5000 micromol/l), ddI (5-1000 micromol/l) and ddC (1-1000 micromol/l) for
      10 days. We evaluated cell proliferation and differentiation and measured lipid
      droplet accumulation, lactate production and respiratory chain enzyme activities.
      All 3 compounds induced a dose-related decrease of cell proliferation and
      differentiation. AZT seemed to be the most potent inhibitor of cell
      proliferation. AZT, ddI and ddC induced cytoplasmic lipid droplet accumulations,
      increased lactate production and decreased activities of COX (complex IV) and SDH
      (part of complex II). NADHR (complex I) and citrate sinthase activities were
      unchanged. Zalcitabine (ddC) and, to a lesser extent, ddI, were the most potent
      inhibitors of mitochondrial function. In conclusion, AZT, ddI and ddC all exert
      cytotoxic effects on human muscle cells and induce functional alterations of
      mitochondria possibly due to mechanisms other than the sole mtDNA depletion. Our
      results provide only a partial explanation of the fact that AZT, but not ddI and
      ddC, can induce a myopathy in HIV-infected patients. AZT myopathy might not
      simply result from a direct mitochondrial toxic effect of crude AZT.

PMID- 9168162
TI  - Asymptomatic pontine lesions found by magnetic resonance imaging: are they
      central pontine myelinolysis?
AB  - Clinicians occasionally receive radiographic reports noting pontine lesions in
      their patients who have undergone magnetic resonance imaging (MRI) for symptoms
      not referable to the pons. Based on these relatively isolated lesions, patients
      may receive the presumptive radiographic diagnosis of central pontine
      myelinolysis (CPM). Review of our MRI database from the last five years
      identified twelve such patients with hyperintense pontine lesions on T2-weighted
      scans which were out of proportion to supratentorial white matter disease
      processes and unexplained by the remainder of their radiographic studies. In an
      attempt to further clarify whether these findings were more consistent with CPM
      or some other process, we reviewed these patients' clinical records with
      particular attention to electrolyte disturbances, alcoholism, liver disease and
      hypertension. We also compared the MRI studies from these twelve patients with
      four MRI scans from patients with clinically diagnosed CPM and with eight post
      mortem MRI scans on autopsy-proven asymptomatic CPM. By comparing pre- and post
      mortem scans, five of the twelve unknown pontine lesions were felt to be too
      large to represent asymptomatic CPM. Five were thought to be incompatible with
      CPM based on shape and/or discohesiveness; one of these came to autopsy and
      showed cerebral and pontine ischemic rarefaction, not CPM. Only two of these
      twelve cases were felt to be asymptomatic or mildly symptomatic CPM, but have not
      come to autopsy. We conclude that pontine lesions found incidentally on MRI scans
      are a heterogeneous group, many of which are more consistent with pontine
      ischemic rarefaction than with asymptomatic CPM.

PMID- 9168163
TI  - A PCR test for progressive external ophthalmoplegia and Kearns-Sayre syndrome on
      DNA from blood samples.
AB  - Progressive external ophthalmoplegia (PEO) and Kearns-Sayre syndrome (KSS) are
      caused by deletions in mitochondrial DNA. Identification of these deletions is
      important for diagnosis, prognosis and genetic counselling. As yet, the most
      frequently used test is Southern blot analysis of DNA isolated from a muscle
      biopsy. Here, we describe a sensitive PCR-based test for the identification of
      these deletions in DNA isolated from blood. The main advantage is that in the
      majority of cases a muscle biopsy is no longer necessary for the molecular
      diagnosis of PEO and KSS.

PMID- 9168164
TI  - T-lymphocyte tumor necrosis factor-alpha receptor binding in patients with
      Parkinson's disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disease of the central nervous
      system (CNS), in which the cytokine network may be deranged, leading to an
      altered immunoregulation. Tumor necrosis factor(TNF)-alpha, a cytokine with
      pleiotropic neuroimmune effects, has specific receptors on human lymphocytes, as
      well as on other cell types, even in the CNS. The aim of the present study was to
      assay TNF-alpha binding on peripheral blood T cells from PD patients, as compared
      with healthy subjects. We found on T lymphocytes from parkinsonian patients
      significantly more TNF-alpha receptors than on those from controls (B (max):
      637+/-23 vs. 131+/-6 (mean+/-S.E.M.) receptors/cell). Such TNF-alpha binding
      sites are of the same type in patients and healthy subjects (K(d): 66.8+/-5.1 vs.
      70.7+/-5.6 (mean+/-S.E.M.) pM). These results are discussed in terms of PD
      immunopathogenesis, since it has been reported that activated T lymphocytes have
      increased amounts of TNF-alpha receptors.

PMID- 9168165
TI  - Electrophysiological analysis of cognitive slowing in Parkinson's disease.
AB  - To analyze chronometrically the evidence for possible cognitive slowing in
      Parkinson's disease, we measured visual event-related potentials (ERPs) and
      reaction times (RTs) in 29 patients with nondemented Parkinson's disease and 19
      age-equivalent normal controls during the performance of semantic discrimination
      tasks. The components of the N1, P2, NA, N2 and P3 and simple and GO/NOGO RTs
      were observed. The N2 was measured from difference waveforms, subtracting the
      ERPs to frequent stimuli from those to infrequent stimuli in the discrimination
      task. Difference waveforms were also derived to delineate NA by subtracting the
      ERPs in the simple RT task from those of the frequent stimuli of the
      discrimination task. The N2 and P3 latencies and GO/NOGO RT in patients with
      Parkinson's disease were significantly longer than those in the controls,
      although there were no differences in N1, P2 and NA latencies or simple RT
      between the two groups. The results are interpreted as electrophysiological signs
      of cognitive slowing, particularly with respect to stimulus classification and
      attention processes in Parkinson's disease, independent of sensory problems. As
      for the automatic/controlled processes, the present results suggest that the
      automatic processing stage associated with NA may be less impaired than the
      attention-controlled processing reflected by N2 in patients with Parkinson's
      disease.

PMID- 9168166
TI  - Transcranial doppler assessment of cerebral flow velocity during perception and
      recognition of melodies.
AB  - The role of each cerebral hemisphere in the perception and recognition of musical
      information is not yet well understood. We studied cerebral blood flow changes
      during a melody perception task and a melody recognition task. Blood flow
      velocity in the two middle cerebral arteries of twenty right-handed musically
      naif volunteers were simultaneously measured by means of bilateral transcranial
      Doppler ultrasonography during two minutes of passive melody listening and two
      minutes of a melody recognition task. With respect to baseline values, a
      bilateral increase of flow velocity occurred in the middle cerebral arteries with
      a non-significant trend for the right artery during the melody perception task.
      During the melody recognition task, a significant increase in flow velocity was
      recorded on the right side with respect to the left side, where a slight
      simultaneous decrease was found. Our data suggest that melody perception requires
      bilateral activation of hemispheres and melody recognition mainly an activation
      of the right hemisphere. This study confirms the ability of transcranial Doppler
      ultrasonography to correlate artery flow dynamics with selective cerebral
      activation.

PMID- 9168167
TI  - The effects of clonazepam and vigabatrin in hyperekplexia.
AB  - Hyperekplexia is an autosomal dominant disorder caused by a point mutation in the
      alpha1 subunit of the glycine receptor, characterized by excessive startle
      responses followed by temporary generalized stiffness. Clonazepam, effective in
      open case studies, potentiates, through unknown mechanisms, the neurotransmitter
      gamma-aminobutyric acid (GABA). Vigabatrin increases GABA by inhibition of the
      GABA catabolic enzyme GABA-transaminase. Effects of clonazepam (1 mg for 1 day)
      and vigabatrin (1000 mg per day for 5 days) were investigated in a double-blind
      placebo-controlled cross-over study in 4 patients with hyperekplexia. The
      pharmacodynamic parameters were startle reflexes, studied 3 times during the day.
      At each time, 2 trains of 10 auditive stimuli (113 dB) were given at intervals of
      10 and 60 s. Startle movements were quantified with summed areas of EMG-bursts of
      the orbicularis oculi, sternocleidomastoid, biceps and thenar muscles. The
      degrees of stiffness and drowsiness were quantified with visual analogue scores
      (VAS) 10 times during the day, by both the patient and the observer. Clonazepam,
      but not vigabatrin, reduced startle activity significantly in both paradigms. The
      degree of stiffness and drowsiness was not significantly influenced by either
      drug.

PMID- 9168168
TI  - Motor evoked potentials recorded from external anal sphincter by cortical and
      lumbo-sacral magnetic stimulation: normative data.
AB  - Electrophysiological activation of the motor pathways can be obtained by
      electrical or magnetic stimulation. The latter has the great advantage of being
      painful and able to stimulate deeply situated nervous structures. Only a few
      reports describe responses obtained from pelvic floor muscles and external anal
      sphincter (EAS) by transcranial and lumbo-sacral magnetic stimulation. Our
      purpose is to present normative data of motor evoked responses from EAS in a
      group of healthy subjects (age range 19-80 years) using a standardized protocol
      of magnetic stimulation. Nine females and 7 males, with a mean age of 52.63
      years, were included in this study. They had no known neurological and
      gastrointestinal disease. Magnetic shocks were delivered by a Magstim 200
      (Novametrix) and a circular coil, centered on the vertex and on the lumbo-sacral
      region. Electromyographic recordings were taken from EAS using needle electrodes.
      The cortical magnetic stimulation was performed in two conditions: at rest and
      during a mild contraction of pelvic floor muscles. The mean values of motor
      evoked potentials (MEPs) latencies after cortical stimulation were 26.92+/-3.01
      ms at rest and 23.31+/-2.70 ms during facilitation. Motor latency after lumbo
      sacral root stimulation was 6.09+/-1.43 ms. The MEPs from EAS are easily obtained
      and stably reproducible in normal subjects. It can be suggested also as a useful
      adjunct in the assessment of faecal incontinence.

PMID- 9168169
TI  - Application of chromosome 4q35-qter marker (pFR-1) for DNA rearrangement of
      facioscapulohumeral muscular dystrophy patients in Taiwan.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) has been found to be linked to
      chromosome 4qter. A chromosome 4q35-ter marker, pFR-1 (subclone of the cosmid
      c51), has been recently isolated and used as a probe for mapping near, or within,
      the FSHD gene. To examine FSHD-associated DNA rearrangements in the Taiwan
      population, we used the pFR-1 probe to perform Southern blot analysis on 142
      individuals, including 32 FSHD patients within 9 autosomal dominant families,
      five sporadic FSHD patients from 4 families (include one pair of twins), three
      sporadic scapuloperoneal syndrome (SPS) patients and two sporadic polymyositis
      patients with their unaffected parents, and 29 healthy controls. In 29 healthy
      individuals, 3 SPS and 2 polymyositis patients with their families, probe pFR-1
      analysis revealed that all had polymorphic restriction fragments that were larger
      than 28 kb in length. All but 1 FSHD-affected individual had specific smaller
      EcoRI fragments (ranging in size from 10.5 to 27 kb). Two point linkage analysis
      between pFR-1 and the FSHD locus provided significant evidence for FSHD linkage
      (Z(max)=6.84). A similar smaller fragment was also present in 5 sporadic
      patients, while this smaller fragment could not be found in one of their parents.
      Identical EcoRI restriction fragment length polymorphism (RFLP) patterns linked
      to FSHD were shown in the monozygotic twins, even though they showed extreme
      variability in the expression of FSHD. We conclude that the pFR-1 probe is a
      tightly linked marker of FSHD and can be used to detect most DNA rearrangements
      associated with this disease in the Taiwan population. However, the same RFLP
      patterns may represent extreme variability in the expression of the FSHD gene.

PMID- 9168170
TI  - Innervation of adult human laryngeal muscle fibers.
AB  - The innervation of laryngeal muscle fibers was appraised in adult humans. Sixteen
      intrinsic laryngeal muscles were dissected during the autopsy of 4 adults (41-71
      years old). Longitudinal serial frozen sections, 60 microm thick, of the whole
      muscles were double-stained for cholinesterase activity and axonal visualization.
      About 945 endplates per muscle were analysed using light microscopy. The
      neuromuscular junctions were always scattered throughout the whole muscles. Most
      of the muscle fibers showed a single neuromuscular junction, but multi-innervated
      fibers were found in all of the muscles. Their number was highest in
      interarytenoid muscles (21% of all the fibers). The distance between multiple
      neuromuscular junctions was most frequently less than 150 microm. Two
      neuromuscular junctions were frequently displayed, opposite one another,
      particularly in thyroarytenoid muscles, and this unusual feature seems specific
      for laryngeal muscles. The innervation of all of the muscle fibers was
      exclusively found to be unineuronal, with multi-innervated fibers being
      innervated by a single axon. Distal axonal degeneration occurred with aging,
      resulting in a loss in the number of multi-innervated muscle fibers.

PMID- 9168171
TI  - Diminished production of type-I interferons and interleukin-2 in patients with
      multiple sclerosis.
AB  - Several lines of evidence have supported the role of immunological mechanisms in
      the pathogenesis of multiple sclerosis (MS) and new immunomodulatory strategies
      for its treatment, e.g. subcutaneous application of interferon (IFN)-beta, have
      emerged. We investigated the ability of peripheral blood mononuclear cells (PBMC)
      in 21 consecutive patients with clinically definite MS to produce interferons and
      lymphokines in response to viral or mitogenic stimulation. Ten patients showed
      clinical signs of disease activity (acute relapse) and 11 patients were in a
      stable condition. Additionally, white blood count, leukocyte differentiation and
      lymphocyte subtyping were performed. A group of age-related healthy blood donors
      served as control (n=20). There was no difference between patients and controls
      in the production of IFN-gamma, tumor necrosis factor (TNF)-alpha and soluble
      interleukin (IL)-2 receptor. IFN-alpha and IFN-beta responsiveness, however, was
      significantly lower in patients with stable disease than in patients with active
      disease and controls (p<0.001). Furthermore, secretion of IL-2 after stimulation
      was significantly diminished in both patient groups as compared to the control
      group (p<0.01). Analysis of T-cell subsets revealed a significantly lower amount
      of CD8+ T-cells in patients with stable disease, leading to a significantly
      higher CD4/CD8 ratio in this group as compared to patients with active disease.
      Our study depicted an IL-2 deficiency in MS patients which is shared with other
      autoimmune diseases. In addition, our findings suggest that the ability to
      produce type-I IFNs, IFN-alpha and IFN-beta, is primarily impaired in MS patients
      and changes in correlation to the course of disease activity.

PMID- 9168172
TI  - Menstrually related worsening of symptoms in multiple sclerosis.
AB  - The objective of this study was to investigate whether the menstrual cycle
      influences multiple sclerosis (MS) symptoms. Seventy-two normally menstruating
      women (aged 20-50 years) with MS were interviewed. Of the 60 patients with a
      relapsing-remitting form of MS (RR-MS), 26 (43%) regularly experienced worsening
      of their MS symptoms in the period just before, or at the beginning of, the
      menstruation. Significantly more patients of the group reporting no influence of
      the premenstrual period on MS symptoms were using an oral contraceptive
      (p=0.041), suggesting a protective effect. There were 12 patients with the
      primary chronic progressive form of MS (PCP-MS). None of them experienced an
      influence of the menstrual cycle on their symptoms. Our results suggest that
      hormonal changes preceding menstruation may worsen symptoms in a subgroup of
      women with RR-MS.

PMID- 9168173
TI  - Longitudinal MR imaging and proton MR spectroscopy in herpes simplex
      encephalitis.
AB  - Longitudinal MR imaging and proton MR spectroscopy were performed in an 11 year
      old female case of herpes simplex encephalitis with a complete recovery. On MR
      imaging, the white matter lesions, which could be seen in the subacute stage, but
      not in the acute or chronic stage, might represent edema due to postinfectious
      neuroallergic phenomena. Proton MR spectroscopy revealed marked reduction of the
      NAA/Cr ratio in the chronic stage, which increased gradually to within normal
      range in a year.

PMID- 9168174
TI  - De novo mutation (Arg98-->Cys) of the myelin P0 gene and uncompaction of the
      major dense line of the myelin sheath in a severe variant of Charcot-Marie-Tooth
      disease type 1B.
AB  - A point mutation (Arg98-->Cys) of exon 3 coding for the extracellular domain of
      the myelin protein zero (P0) gene was found in a sporadic case of an eighteen
      year old Japanese man with a severe variant of Charcot-Marie-Tooth disease type
      1B (CMT1B). A de novo mutation was established by parentage testing and analyses
      of the P0 gene in the family. This patient showed delayed motor development,
      nonprogressive limb weakness and kyphoscoliosis. In addition to the nerve biopsy
      findings typical of CMT1B, such as segmental demyelination, marked decrease in
      the density of myelinated fibers, and frequent onion-bulb formation,
      ultrastructural examination disclosed uncompaction of the major dense lines with
      slight widening of the intraperiod distance in the inner layers of the myelin
      sheath. Although mutations in the extracellular domain of P0 should affect
      homophilic adhesion between external surfaces of Schwann cell processes,
      resulting in the separation at the intraperiod lines, our study shows uncompacted
      major dense lines as a main myelin abnormality where the cytoplasmic domain of P0
      resides.

PMID- 9168175
TI  - Clinical heterogeneity in respiratory chain complex III deficiency in childhood.
AB  - Six children are presented with an isolated complex III deficiency in muscle
      tissue. More specifically, oxidation rates and ATP+CrP production rates from both
      pyruvate and succinate as substrates and/or the activity of
      decylubiquinol:cytochrome c oxidoreductase were all markedly reduced. Complex III
      deficiency was also present in liver of two patients tested, but could not be
      demonstrated in cultured fibroblasts of four patients tested. Mitochondrial DNA,
      extracted from muscle, was analyzed; no deletions or common point mutations were
      found. Four patients presented with a multi-organ disorder. Among these patients
      three presented at neonatal age with neurological signs and lactate elevation in
      blood and CSF, of whom two had severe neonatal Fanconi syndrome. One child, aged
      seven years, had encephalomyopathy, ophthalmoplegia, retinopathy and Wolff
      Parkinson-White syndrome. The remaining two patients exhibited myopathy only,
      within the first year of life. Thus, like in other respiratory chain disorders,
      patients with complex III deficiency may present at any age and show variable
      symptoms and outcome, ranging from neonatal death to failure to thrive only.
      Apparently there are no clinical findings which are specific for complex III
      deficiency.

PMID- 9168176
TI  - Screening for CDKN2A mutations in hereditary melanoma.

PMID- 9168177
TI  - Urokinase-type plasminogen activator and its receptor in bladder cancer.

PMID- 9168178
TI  - Cancer risk high, but lower than expected with breast cancer genes.

PMID- 9168179
TI  - Potential drug DHEA hits snags on way to clinic.

PMID- 9168180
TI  - Green tea, mistletoe, and more: Canadians test alternative cancer therapies.

PMID- 9168181
TI  - IOM study will probe NIH-supported cancer research affecting minorities.

PMID- 9168182
TI  - Clinical trials need more ethnic balance.

PMID- 9168183
TI  - Androgen deprivation as a strategy for prostate cancer chemoprevention.

PMID- 9168184
TI  - Screening of germline mutations in the CDKN2A and CDKN2B genes in Swedish
      families with hereditary cutaneous melanoma.
AB  - BACKGROUND: Approximately 10% of human cutaneous melanomas occur in families in
      which several members are affected. The familial predisposition to this disease
      is often associated with dysplastic nevus syndrome, a condition in which
      afflicted family members have multiple dysplastic nevi (atypical moles). The
      chromosome region 9p21 and markers on chromosomes 1p and 6p have been linked to
      melanoma susceptibility. The tumor suppressor genes CDKN2A and CDKN2B have been
      mapped to the 9p21 region, and genetic analyses have revealed the presence of
      germline CDKN2A alterations in melanoma families. The reported frequencies of
      such alterations, however, vary among these families. PURPOSE: The present
      investigation was carried out to determine the frequencies of CDKN2A and CDKN2B
      germline gene mutations among members in a population-based cohort of Swedish
      melanoma families (i.e., melanoma kindreds). METHODS: DNA was prepared from blood
      samples obtained from 181 individuals belonging to 100 melanoma kindreds. The
      polymerase chain reaction (PCR) technique, followed by single-strand conformation
      polymorphism (SSCP) and nucleotide sequence analyses, were used to identify the
      types and frequencies of mutations in exons 1, 1beta, 2, and 3 of the CDKN2A gene
      and in exons 1 and 2 of the CDKN2B gene. RESULTS: CDKN2A gene aberrations were
      independently identified by both SSCP and nucleotide-sequence analyses.
      Nucleotide-sequence analysis identified a single point mutation leading to a
      substitution of leucine for proline in codon 48 of exon 1 in a family with a
      history of melanoma and several other cancers. A second abnormality, leading to
      an insertion of an extra arginine residue at codon number 113 of exon 2, was seen
      in four separate families. The CDKN2A exon-3 coding region had the wild-type
      sequence in all samples. No germline mutations were found in the alternative exon
      1beta of the CDKN2A gene or in exons 1 and 2 of the CDKN2B gene. CONCLUSIONS: The
      present investigation demonstrates that CDKN2A germline gene mutations were
      observed in 7.8% of the 64 Swedish melanoma kindreds that each included at least
      two first-degree relatives with melanoma and dysplastic nevus syndrome. No CDKN2A
      exon 1beta or CDKN2B mutations were identified. The critical genes responsible
      for the inheritance of a susceptibility to develop melanoma among family members
      in this population have yet to be identified.

PMID- 9168185
TI  - Enhancing adherence following abnormal Pap smears among low-income minority
      women: a preventive telephone counseling strategy.
AB  - BACKGROUND: Although the incidence of precancerous conditions of the cervix has
      recently been increasing, prompt initial and long-term follow-up care can
      effectively reduce unnecessary morbidity and mortality. For example, the 4-year
      survival rates among those individuals at greatest risk for cervical cancer
      (i.e., minority women of low socioeconomic status) approach 95% with early
      detection. Women who present with advanced disease have a much poorer outlook (0%
      39% survival). Yet, high-risk individuals are least likely to adhere to
      recommended diagnostic regimens. PURPOSE: We tested the effectiveness of a brief
      telephone counseling intervention directed to low-income, inner-city women after
      they had received an abnormal Pap smear result. The women were counseled on the
      importance of having an initial and 6-month repeat follow-up diagnostic procedure
      (i.e., colposcopic examination of the cervix). METHODS: A randomized trial design
      was used to compare the effects on these women of telephone counseling with (n =
      192) or without (n = 203) a booster counseling telephone call prior to the
      appointment for a repeat colposcopy 6 months later, with a telephone appointment
      confirmation/reminder call (n = 216) and with standard care (i.e., no telephone
      contact) (n = 217). The telephone counseling protocol probed for and addressed
      three psychologic barriers to adherence (i.e., attendance at appointment for
      colposcopy examination): 1) encoding/expectancy (e.g., did the patient understand
      her risk of developing cervical cancer?); 2) affective/emotional (e.g., was the
      woman worried about the condition and its consequences?); and 3) self
      regulatory/practical (e.g., was the woman likely to forget medical
      appointments?). Logistic regression was used to analyze the effects of the
      intervention group and the type of psychologic barriers elicited on colposcopy
      adherence. RESULTS: The results of logistic regression analysis (using those who
      received an appointment confirmation/reminder telephone call as the comparison
      group) revealed that telephone counseling produced significantly higher adherence
      rates to the initial colposcopy visit compared with telephone confirmation (300
      [76%] of 395 women versus 147 [68%] of 216; odds ratio [OR] = 1.50; 95%
      confidence interval [CI] = 1.04-2.17). Additionally, standard care resulted in
      significantly lower adherence rates than did telephone confirmation (109 [50%] of
      217 women versus 147 [68%] of 216; OR = 0.47; 95% CI = 0.32-0.73). Regarding
      attendance at the 6-month repeat colposcopy appointments, the 80 patients who had
      received telephone counseling prior to the initial visit (and were recommended
      for follow-up colposcopy) were significantly more likely to adhere than were the
      47 patients who had received telephone confirmation (49 [61%] of 80 women versus
      17 [36.2%] of 47; OR = 2.70; 95% CI = 1.15-6.51). The 6-month adherence rates for
      patients in the telephone confirmation group and the standard care group (n = 30)
      were low and did not differ significantly (17 [36.2%] of 47 women versus nine
      [30.0%] of 30; OR = 1.08; 95% CI = 0.40-2.89). Forgetting medical appointments
      (OR = 0.31; 95% CI = 0.19-0.51) and having scheduling conflicts (OR = 0.45; 95%
      CI = 0.28-0.72) were also associated with lower rates of adherence. CONCLUSION:
      The use of telephone counseling appears to be an effective strategy for enhancing
      initial and long-term adherence to a follow-up cervical diagnostic procedure in a
      traditionally underserved population. Patients who respond to a positive Pap test
      result with a particular profile of psychologic barriers may require more
      intensive and targeted counseling interventions.

PMID- 9168186
TI  - Urokinase and the urokinase receptor: association with in vitro invasiveness of
      human bladder cancer cell lines.
AB  - BACKGROUND AND PURPOSE: The plasminogen activators urokinase and tissue
      plasminogen activator are enzymes that degrade proteins in tissue basement
      membranes and the extracellular matrix (a biomolecular complex surrounding
      individual cells in tissues that serves as a barrier between the cells and the
      vascular and lymph systems). The action of these enzymes allows tumor cells to
      escape their local environment and metastasize. Plasminogen activator activity
      can be influenced by the urokinase receptor, which is expressed on the surface of
      cells, and by the plasminogen activator inhibitors 1 and 2. Because bladder
      tumors differ in their propensity to invade local areas and distant sites, we
      studied the expression of both plasminogen activators, the two plasminogen
      activator inhibitors, and the urokinase receptor in four human bladder cancer
      cell lines (RT4, 253J, EJ, and T24) to see if there was an association between
      the expression of these proteins and tumor cell invasiveness in vitro. METHODS:
      The expression of urokinase, tissue plasminogen activator, and the two inhibitors
      was measured by enzyme-linked immunosorbent assays of serum-free, cell
      conditioned media (i.e., culture fluids). Cell surface expression of the
      urokinase receptor was assayed by flow cytometry, using an anti-receptor
      monoclonal antibody (Mab3936). The invasive capacity of untreated cells and of
      cells exposed to exogenous, high-molecular-weight urokinase was analyzed by use
      of Matrigel invasion chambers. RESULTS: The four bladder cancer cell lines
      demonstrated differential expression of both plasminogen activators and both
      inhibitors; three of the cell lines (T24, EJ, and 253J) expressed the urokinase
      receptor. The four cell lines differed in their invasive potential in vitro.
      Neither expression of tissue plasminogen activator nor production of the
      inhibitors appeared to influence Matrigel invasion. EJ cells and 253J cells
      produced the highest levels of urokinase and demonstrated the greatest propensity
      for invasion; T24 cells, which produced only small amounts of urokinase,
      exhibited a low invasive potential. Pretreatment of T24 cells with exogenous high
      molecular-weight urokinase markedly increased their invasiveness. Similar
      pretreatment of EJ and 253J cells increased their invasiveness as well. RT4
      cells, which lacked urokinase receptor expression but produced moderate amounts
      of urokinase, were not invasive and did not become so after exposure to exogenous
      high-molecular-weight urokinase. Binding of Mab3936 to urokinase receptors
      inhibited Matrigel invasion. CONCLUSIONS: To our knowledge, this is the first
      study demonstrating that bladder tumor cells express the urokinase receptor and
      that both receptor expression and urokinase expression are required for bladder
      tumor cell invasion in vitro.

PMID- 9168187
TI  - Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol
      treatment in humans.
AB  - BACKGROUND: The oxidative metabolism of estrogens in humans is mediated primarily
      by cytochrome P450, many isoenzymes of which are inducible by dietary and
      pharmacologic agents. One major pathway, 2-hydroxylation, is induced by dietary
      indole-3-carbinol (I3C), which is present in cruciferous vegetables (e.g.,
      cabbage and broccoli). PURPOSE: Because the pool of available estrogen substrates
      for all pathways is limited, we hypothesized that increased 2-hydroxylation of
      estrogens would lead to decreased activity in competing metabolic pathways.
      METHODS: Urine samples were collected from subjects before and after oral
      ingestion of I3C (6-7 mg/kg per day). In the first study, seven men received I3C
      for 1 week; in the second study, 10 women received I3C for 2 months. A profile of
      13 estrogens was measured in each sample by gas chromatography-mass spectrometry.
      RESULTS: In both men and women, I3C significantly increased the urinary excretion
      of C-2 estrogens. The urinary concentrations of nearly all other estrogen
      metabolites, including levels of estradiol, estrone, estriol, and 16alpha
      hydroxyestrone, were lower after I3C treatment. CONCLUSIONS: These findings
      support the hypothesis that I3C-induced estrogen 2-hydroxylation results in
      decreased concentrations of several metabolites known to activate the estrogen
      receptor. This effect may lower estrogenic stimulation in women. IMPLICATIONS:
      I3C may have chemopreventive activity against breast cancer in humans, although
      the long-term effects of higher catechol estrogen levels in women require further
      investigation.

PMID- 9168188
TI  - Detection of telomerase activity in exfoliated cells in urine from patients with
      bladder cancer.
AB  - BACKGROUND: Telomeres are specific structures located at the ends of chromosomes
      that help maintain chromosome stability. In most tissues, telomeres become
      shorter as cells divide, a phenomenon thought to be associated with limitations
      on normal cell proliferation. Almost all types of cancer cells, including bladder
      cancer cells, express the enzyme telomerase, which can maintain or extend
      telomere length. PURPOSE: We examined telomerase activity in tumor specimens from
      a cohort of patients with bladder cancer and determined whether telomerase could
      be detected in exfoliated cancer cells present in urine from these patients.
      METHODS: Spontaneously voided urine specimens and bladder-washing fluids
      (obtained by propelling normal saline into the bladder through a catheter and
      then withdrawing the liquid contents) were taken from 45 patients before they
      underwent surgery. Telomerase activity was examined by means of the TRAP
      (telomeric repeat amplification protocol) assay on extracts of tumor samples from
      42 patients and extracts of exfoliated cells in urine and bladder-washing fluid
      from 42 and 43 patients, respectively. Standard cytologic examination (Pap
      staining) of urine specimens was also used to detect exfoliated cancer cells.
      RESULTS: Telomerase activity was found in 41 (98%; 95% confidence interval [CI] =
      87%-100%) of the 42 tumor samples examined. In contrast, it was not detected in
      normal bladder tissue from two autopsied individuals who were free of bladder
      cancer and five of six individuals who had bladder cancer. Telomerase was
      detected in exfoliated cells in 23 (55%; 95% CI = 39%-70%) of the 42
      spontaneously voided urine specimens and in 36 (84%; 95% CI = 69%-93%) of the 43
      bladder-washing fluids examined. Considering voided urine specimens and bladder
      washing fluids together, telomerase was detected in exfoliated cells from 40
      (89%; 95% CI = 76%-96%) of the 45 patients. Telomerase activity was not detected
      in bladder-washing fluids from 12 cancer-free individuals. Cancer cells were
      detected by means of standard cytologic examination in the urine of 19 (42%; 95%
      CI = 28%-58%) of the 45 patients. Urine cytologic examination detected cancer
      cells in one (8%; 95% CI = 0%-38%) of 12 patients with grade 1 tumors and in 13
      (46%; 95% CI = 28%-66%) of 28 patients with grade 2 tumors. In contrast,
      telomerase activity was detected in exfoliated cells (in voided urine or bladder
      washing fluids) from nine (75%; 95% CI = 43%-95%) of 12 patients with grade 1
      tumors and from 27 (96%; 95% CI = 82%-100%) of 28 patients with grade 2 tumors.
      CONCLUSION AND IMPLICATION: Telomerase activity can be detected in exfoliated
      cells in urine from patients with bladder cancer, and measurement of this
      activity appears to be more sensitive in detecting the presence of cancer than
      standard urine cytologic examination. These findings suggest that measuring
      telomerase activity in exfoliated cells would be useful in the diagnosis and
      follow-up of patients with bladder cancer, a possibility that warrants further
      study.

PMID- 9168189
TI  - Acceptable strategies for dealing with hereditary breast/ovarian cancer risk.

PMID- 9168190
TI  - Age, cohort-of-birth, and period-of-death trends in breast cancer mortality in
      Europe.

PMID- 9168192
TI  - Monitoring of aromatic amine exposures in workers at a chemical plant with a
      known bladder cancer excess.

PMID- 9168191
TI  - Monitoring of aromatic amine exposures in workers at a chemical plant with known
      bladder cancer excess.

PMID- 9168193
TI  - A hidden paradox in carcinogenesis bioassays.

PMID- 9168195
TI  - Microtubule-associated proteins, phosphorylation gradients, and the establishment
      of neuronal polarity.
AB  - Axonogenesis is the earliest step in acquisition of neuronal polarity. The
      subcellular mechanisms underlying this pivotal event are unknown. Because of the
      abundant presence and functional necessity of microtubule-associated proteins in
      growing neurites, a large effort has been directed at characterizing their role
      in establishment and maintenance of neuronal polarity. One unsolved puzzle is how
      MAPs, most of which are unpolarized in early stages of development, can locally
      influence microdifferentiation of axons and dendrites. In this review, we discuss
      recent evidence suggesting that locally controlled phosphorylation of microtubule
      associated proteins tau and MAP1B may play a role in establishment of polarity
      and early axonal outgrowth.

PMID- 9168194
TI  - The cytoskeleton in nerve growth cone motility and axonal pathfinding.
AB  - Axonal pathfinding occurs through detection of environmental cues by cytoskeletal
      machinery that is responsible for growth cone migration. The cycle of filopodial
      and lamellipodial protrusion, adhesion, and generation of tensions to advance a
      growth cone result from concerted actions of ABPs to regulate actin filament
      polymerization, assembly into networks and bundles, and production of tension to
      move the growth cone and its contents. The direction of neurite elongation is
      controlled by forward movement of microtubules in growth cones, which is
      pioneered by the advance of microtubules into P domain of the leading margin.
      Actin filaments both promote and impede this advance of microtubules in several
      ways. This cytoskeletal machinery is controlled by major signaling mechanisms. To
      understand growth cone guidance we must reveal the spatial and temporal changes
      generated in [Ca++]i, phospholipids, and protein phosphorylation and
      dephosphorylation, and then identify the ABPs and MAPs that are their targets.

PMID- 9168196
TI  - Molecular mechanisms of directed growth cone motility.
AB  - Establishing molecular mechanisms of axon guidance presents one of the greatest
      challenges in understanding the development of the nervous system. There are many
      neurons, and each neuron by virtue of its location, biochemistry, and time of
      development, may generate a unique axon morphology in its response to
      environmental cues that may also change during development. The context
      dependence and combinatorial nature of these interactions make analysis of axon
      guidance particularly difficult. This article will focus on the neuronal growth
      cone as axon guidance is controlled by interaction of the growth cone with its
      environment. I present here an overview of growth cone motility from the
      perspective of cytoskeletal dynamics. I conclude with a discussion of our
      application of regional laser inactivation of growth cone proteins to address
      what proteins might be involved in locally modulating the cytoskeleton and how
      they affect growth cone motility.

PMID- 9168198
TI  - Shared cell adhesion molecule (CAM) homology domains point to CAMs signalling via
      FGF receptors.
AB  - A number of cell adhesion molecules (CAMs) promote neurite outgrowth following
      transfection and expression in a variety of monolayer cells. We have shown that N
      cadherin, L1 and some isoforms of NCAM can stimulate neurite outgrowth from PC12
      cells and primary neurons following transfection and expression at
      physiologically relevant levels in NIH-3T3 cells. A number of observations
      suggest that these CAMs stimulate neurite outgrowth by activating a convergent
      second messenger pathway in neurons rather than by modulating adhesion per se,
      and that an early or initial step in the pathway involves activation of a
      tyrosine kinase. The observation that the fibroblast growth factor receptor
      (FGFR) contains an evolutionarily conserved sequence with homology to the above
      CAMs (the CAM homology domain-CHD) points to the possibility that CAMs might
      interact with, and signal via, FGFR tyrosine kinases. This hypothesis has been
      substantiated by a number of independent experimental tests. We present a
      speculative model in which the evolutionary conservation of a pair of
      complementary binding motifs can account for a direct binding interaction between
      FGFR and the above three CAMs.

PMID- 9168197
TI  - Intracellular mechanisms of axon growth induction by CAMs and integrins: some
      unresolved issues.
AB  - Integrins and cell adhesion molecules (CAMs) are important neuronal receptors
      mediating substrate-induced axon growth. Signaling of axon growth through these
      receptors involves both regulation of tyrosine phosphorylation and transient
      increases in intracellular Ca2+. Many of the details concerning these signal
      transduction events and mechanisms through which they regulate effectors of axon
      growth are poorly understood. This review discusses some of the gaps in our
      current knowledge, with suggestions on approaches to closing these gaps. Emphasis
      is on the role of tyrosine phosphatases in the regulation of axon growth, the
      origin and nature of Ca2+ signals produced by stimulation of CAMs and integrins,
      and possible links of these two pathways to cytoskeletal rearrangements and
      directed addition of plasma membrane.

PMID- 9168199
TI  - Selective neural cell adhesion molecule signaling by Src family tyrosine kinases
      and tyrosine phosphatases.
AB  - Nerve growth cone guidance is a highly complex feat, involving coordination of
      cell adhesion molecules, trophic factor gradients, and extracellular matrix
      proteins. While navigating through the developing nervous system, the growth cone
      must integrate diverse environmental signals into a singular response. The
      repertoire of growth cone responses to these extracellular cues includes axonal
      growth, fasciculation, and synaptic stabilization, which are achieved through
      dynamic changes in the cytoskeleton and modulation of gene expression. It has
      become evident that interactions between cell adhesion molecules can activate
      intracellular signaling pathways in neurons. Such signaling pathways are just
      beginning to be defined for the axonal growth promoting molecules L1 and NCAM
      which are members of the immunoglobulin (Ig) superfamily. Recent findings have
      revealed that L1 and NCAM induce neurite outgrowth by activating intracellular
      signaling pathways in the growth cone mediated by two different members of the
      src family of nonreceptor protein tyrosine kinases (PTKs), pp60(c-src) and
      p59(fyn5,6). Growth cones display diverse morphologies and variable motility on
      these different cell adhesion molecules, which are likely to be generated by src
      kinases. In this review we will address novel features of nonreceptor PTKs of the
      src family which dictate their distinctive molecular interactions with cell
      adhesion molecules and signaling components.

PMID- 9168200
TI  - Tyrosine phosphorylation and protrusive structures of the growth cone.
AB  - Protein-tyrosine kinase, such as those of the trk and Eph families, serve as
      membrane receptors for extracellular cues which regulate the rate and direction
      of growth of numerous groups of axons. Certain cytoplasmic protein-tyrosine
      kinases, such as src, are also abundant in growth cones. But, how protein
      tyrosine phosphorylation regulates the growth cone is poorly understood. We
      discuss here potential roles for tyrosine phosphorylation in the protrusive
      structures of the growth cone, especially filopodia, which are important in
      detecting cues. A particular focus is the integrin receptor for substrate-bound
      growth promoters like laminin. Changes in tyrosine phosphorylation may be
      important in both facilitating and mediating the interaction of filopodia with
      these growth promoters.

PMID- 9168201
TI  - GAP-43: putting constraints on neuronal plasticity.
AB  - The brain must balance the need for synaptic precision with the ability to
      generate and change connectivity patterns in response to environmental stimuli.
      GAP-43 is a phosphoprotein associated with the cytosolic surface of the membrane,
      and is one of the most abundant among the small subset of total cellular proteins
      transported to the growth cone. It appears to play an unusual role amplifying
      signals from the microenvironment. One of the several ways to perform this task
      involves interaction of GAP-43 with the G protein transduction cascade. In mice
      rendered GAP-43 null by homologous recombination, some nerves manifest aberrant
      growth at decision points, such as the optic chiasm. Thus, GAP-43 may work via
      modulation of signaling cascades, rather than autonomously causing growth, and
      could serve to keep plasticity within constraints needed to generate and maintain
      accurate synaptic wiring.

PMID- 9168202
TI  - Small GTPases in axon outgrowth.
AB  - We propose that small GTPases in the Rho/Rac/Cdc42 subfamily play a central role
      in signaling pathways from cell surface receptors to actin cytoskeleton changes
      in the growth cone. The proposal is based upon the following evidence. First, the
      Rho/Rac/Cdc42 subfamily GTPases have been shown to regulate various aspects of
      cytoskeletal organization from budding yeast to mammalian fibroblasts. Second,
      perturbation of GTPase activities of Rac and Cdc42 in neurons by constitutively
      active and dominant negative mutants results in specific defects in axon and
      dendrite outgrowth. In addition to reviewing existing experimental evidence, we
      will discuss the implications of such a model and the potential relationship with
      other signaling pathways.

PMID- 9168203
TI  - Calcium and chemotropic turning of nerve growth cones.
AB  - Cultured Xenopus spinal neurons exhibit chemotropic turning toward the source of
      neurotransmitters acetylcholine and glutamate. Here we review the experimental
      evidence that transmitter-induced turning of the growth cone is mediated by an
      influx of Ca2+, that a gradient of intracellular Ca2+ within the growth cone is
      responsible for the directional growth cone response, and that asymmetric
      filopodia formation precedes and is essential for the turning response.

PMID- 9168204
TI  - Functional compartmentalization of the neuronal growth cone: determining
      calcium's place in signaling cascades.
AB  - The growth cone is generally regarded as the basic unit of neuronal organization
      concerned with development of connections within the nervous system. The
      discussion below illustrates that the growth cone itself can be subdivided into
      distinct units of organization. It is this functional compartmentalization which
      enables the growth cone to read the molecular terrain it traverses and to convert
      this information into precise motor events. Our discussion will focus on the flow
      of information from the environment to the growth cone. In particular, we will
      follow signaling events from their remote processing within filopodia to the
      biological equivalent of a central processing unit in the core of the growth
      cone.

PMID- 9168205
TI  - Signal transduction during axon guidance: a genetic analysis in Drosophila.
AB  - The searching growth cone simultaneously processes multiple guidance cues and
      converts them into intracellular signals regulating axon extension, steering and
      eventually synapse formation. This overlap of signaling pathways ensures
      functional connectivity of the nervous system during development. While this
      complicates the genetic analysis of these signaling pathways, combination of
      genetic techniques available in Drosophila has begun to successfully address the
      role of some key signaling molecules during axon guidance.

PMID- 9168206
TI  - Investigations of signaling pathways in axon growth and guidance.
AB  - The retinotectal projection in chick is a well studied model system for axon
      guidance. The 'stripe assay' provides a unique tool for investigating underlying
      molecules and mechanisms of axon guidance by non-diffusible substrate bound
      molecules in vitro. By combining this assay with a modified 'Campenot chamber',
      we have now investigated the role of several second messenger systems in this
      type of axon guidance by confronting growing axons with various drugs that are
      known to influence intracellular signaling. We have shown that extracellular, and
      most probably intracellular Ca++ is not required for this type of axon guidance,
      which also rules out the need for Ca++-dependent adhesion molecules like
      cadherins. While at least calmodulin and protein kinase C seem to be involved in
      axon elongation, inhibiting their function did not alter the growth cones'
      choice. Inhibition of other kinases, G-proteins and signaling components also
      failed to influence this guidance. These results may indicate that parallel
      signaling pathways take part in the molecular mechanism of this type of axon
      guidance.

PMID- 9168207
TI  - Signal transduction in vertebrate growth cones navigating in vivo.
AB  - Navigating growth cones need signal transduction machinery to amplify and
      transmit the effects of extracellular signals throughout the growth cone. In
      culture, many drugs that affect second messengers are known to modulate neurite
      extension (with different effects on different neurons), and gradients of calcium
      influx and cyclic nucleotide analogs can cause growth cones to turn. However, it
      is not clear which of these responses are physiologically relevant, as axons grow
      through much more complex environments in vivo. The "exposed brain" preparation
      in Xenopus embryos provides an experimentally tractable system in which it is
      possible to study growth, pathfinding, and target recognition of retinal growth
      cones in vivo, while pharmacologically manipulating their signal transduction
      systems. These growth cones can also be easily studied in explant culture. We
      describe preliminary results of parallel in vivo and in vitro experiments using
      an array of drugs that perturb transduction molecules. Surprisingly, calcium
      ionophores and cyclic nucleotide analogs have no significant effect on retinal
      axon growth or pathfinding. Several agents including herbimycin A, ML-7,
      mastoparan, and RHC80267 inhibit retinal axon growth, both in vivo and in vitro,
      suggesting that tyrosine kinases, myosin, heterotrimeric G-proteins, and
      diacylglycerol lipase are important for retinal growth cones navigating in the
      optic pathway.

PMID- 9168208
TI  - Where should advocacy for pediatric patients end and concerns for patient safety
      begin?

PMID- 9168209
TI  - QA in regional anesthesia training: quantity or quality?

PMID- 9168210
TI  - Single-injection lumbar epidural morphine for postoperative analgesia in
      children: a report of 175 cases.
AB  - BACKGROUND AND OBJECTIVES: Since the first report of epidural opioid
      administration to pediatric patients, several studies have described the quality
      of analgesia, doses, pharmacokinetics, and side effects of this procedure. A
      pediatric series using an easy and cheap single-injection technique of epidural
      morphine administration for postoperative analgesia is presented. METHODS:
      Postoperative analgesia was achieved with a single lumbar epidural morphine
      injection (0.1 mg/kg in 0.2 mL/kg saline), which was given via a 22-gauge
      intramuscular needle to 153 pediatric patients (aged 4 months-17 years) following
      175 lower abdominal or urologic operations. Injections were given by 43
      anesthesiology residents under the supervision of pediatric anesthesiologists,
      after termination of surgery performed under general anesthesia. RESULTS: The
      success rate of epidural puncture on the first attempt was 92%. Pain control was
      considered excellent in 76% of patients for 24 hours. The remaining patients had
      analgesia lasting 10.9 +/- 5.5 hours after epidural morphine administration. No
      alterations in hemodynamic parameters were observed. Two patients (1.1%)
      developed respiratory depression during early postoperative care and one, with a
      history of apneic spells, had an episode of apnea 5 hours after morphine
      administration. The incidences of minor side effects were: nausea, 33.9%;
      vomiting, 42.9%; pruritus 9%; and urinary retention 12.5%. CONCLUSIONS: This
      technique is easy to perform, even for trainees in anesthesiology. With
      appropriate patient selection and avoidance of the concomitant use of narcotics
      and sedatives, epidural morphine provides prompt, effective, safe, and prolonged
      analgesia in children.

PMID- 9168212
TI  - The parasacral sciatic nerve block.
AB  - BACKGROUND AND OBJECTIVES: The clinical utility of a new parasacral approach for
      conduction block of the sciatic nerve was investigated, with critical examination
      of onset, extent, and success rates when this block was used for surgical
      procedures below the knee. METHODS: Thirty ASA I-III patients presenting for
      surgery on the lower limb were enrolled. All received 30 mL of 1.5% lidocaine
      with 1:200,000 epinephrine following nerve stimulator identification of the
      sciatic nerve at < or =0.2 mA or less. Trans-sartorial saphenous nerve blocks
      were performed to provide anesthesia to the medial leg. RESULTS: Overall success
      for surgical anesthesia with this block was 97%. All components of the sacral
      plexus could be blocked with this approach, and 93% of patients displayed
      evidence of obturator nerve motor block. However, no patient displayed evidence
      of obturator sensory anesthesia that could be mapped. Saphenous nerve blocks were
      100% effective in providing surgical anesthesia for the procedures performed.
      CONCLUSIONS: The parasacral approach to the sciatic nerve exhibits a high success
      rate, resulting in anesthesia of the entire sacral plexus and generally in motor
      block of the obturator nerve was an interesting observation.

PMID- 9168211
TI  - Survey of regional anesthetic practice among French residents at time of
      certification.
AB  - BACKGROUND AND OBJECTIVES: A survey of anesthesia practice was conducted among
      French residents in anesthesia at the end of their training. This study was
      performed mainly to evaluate the residents' experience in peripheral nerve
      blocks. METHODS: Two short clinical cases were proposed to all French residents
      during a telephone interview immediately before their certification. The first
      described the case of a young asthmatic patient admitted for an elbow fracture.
      The second described an elderly woman with severe aortic stenosis admitted for a
      supracondylar fracture of the femur. A questionnaire had been prepared and was
      filled in during the interview. Each resident was asked to answer according to
      the actual choice he or she would have made. For both cases, when general
      anesthesia was chosen first, the next question was to discuss which regional
      anesthesia would be used if general anesthesia had to be discarded. In that way,
      the practical knowledge about most common peripheral nerve blocks learned during
      residency was investigated. RESULTS: Of 77 residents registered as being at the
      end of their residency, 8 were on either sabbatical or maternity leave. Regional
      anesthesia was the first choice in 78% and 57% of cases for the first and second
      clinical cases, respectively. The regional anesthetic techniques chosen were
      axillary block (66%), interscalene block (31%), and intravenous regional
      anesthesia (3%) for case 1 and combined lumbar plexus and sciatic block (36%),
      epidural anesthesia (30%), single-shot spinal anesthesia (18%), and continuous
      spinal anesthesia (16%) for case 2. Throughout the residency of the group, 32 +/-
      2 axillary blocks, 12 +/- 2 interscalene blocks (axillary vs interscalene, P <
      .0001), 21 +/- 3 femoral blocks, and 10 +/- 2 sciatic blocks (femoral vs sciatic,
      P < .0001) had been performed (mean +/- SEM). They had also performed 2.5 +/- 0.5
      continuous spinal anesthesias and 17 +/- 3 intravenous regional anesthesias
      respectively. Upper extremity blocks were more often used during residency than
      lower extremity blocks (44 +/- 3 vs 31 +/- 4, P < .01). A peripheral nerve
      stimulator was routinely used by 83% of residents. CONCLUSION: French residents
      in anesthesiology at time of certification are better trained for peripheral
      nerve blocks of the upper extremity than for those of the lower extremity.
      Axillary plexus and femoral nerve block are the most widely used blocks, probably
      reflecting the techniques the most mastered among teachers. Finally, the
      extensive use of a peripheral nerve stimulator by residents is probably the
      result of the widespread use of this device by teachers in France.

PMID- 9168214
TI  - Pain relief after knee arthroscopy: intra-articular morphine, intra-articular
      bupivacaine, or subcutaneous morphine?
AB  - BACKGROUND AND OBJECTIVES: This investigation was undertaken to compare analgesic
      effects, side effects, and requirements for supplemental analgesic therapy after
      knee arthroscopy in patients given intra-articular (IA) or subcutaneous (SC)
      morphine, intra-articular bupivacaine, or placebo. METHODS: In a randomized,
      double-blind controlled trial, 112 patients, 14-65 years old each received two
      solutions, one SC and the other IA. Group IAM (n = 30) received 10 mg IA morphine
      in 20 mL normal saline plus 1 mL of SC normal saline Group IAB (n = 27) received
      20 mL IA bupivacaine 0.5% with IA epinephrine plus 1 mL SC normal saline Group
      SCM (n = 26) received 20 mL IA normal saline plus 10 mg SC morphine in 1 mL.
      Group P (n = 29) received 20 mL IA normal saline plus 1 mL SC normal saline. Pain
      was evaluated on arrival in the postanesthesia care unit (PACU), and 30, 45, 60,
      90, and 120 minutes afterwards. If pain exceeded 4/10 on a visual analog pain
      scale in the PACU, 30 mg intravenous ketorolac was given, and if pain persisted,
      0.4 mg hydromorphone was added every 7 minutes. After PACU discharge, patients
      whose pain exceeded 4/10 received oral ketorolac 10 mg every 6 hours; oral
      acetaminophen plus codeine was added every 4 hours if pain still exceeded 4/10.
      Analgesic requirements, along with visual analog pain score, sedation, and nausea
      were recorded every 6 hours for 72 hours. RESULTS: All three active (nonplacebo)
      pain treatments provided good pain control in the PACU. Side effects were similar
      in all groups. The placebo group had higher pain scores at 120 minutes (R = .02),
      higher supplemental analgesic requirements at 60 minutes (P = .04) and 90 minutes
      (P = .02) and the highest amount of total opioid rescue dose (P = .04). Patients
      in groups IAB and P had higher visual analog pain scores at 6 hours (P = .04) and
      30 hours (P = .049) than those in Groups IAM and SCM. CONCLUSION: A single 10-mg
      dose of morphine given either IA or SC provides better and longer-lasting
      postoperative pain relief after knee arthroscopy than 20 mL IA bupivacaine 0.5%
      with epinephrine.

PMID- 9168213
TI  - Use of preincisional ketorolac in hernia patients: intravenous versus surgical
      site.
AB  - BACKGROUND AND OBJECTIVES: This study was designed to determine whether
      administration of ketorolac directly in the surgical site results in enhanced
      analgesia. METHODS: A randomized double-blind study was undertaken at a
      university-affiliated tertiary care hospital. Thirty outpatients undergoing
      unilateral inguinal hernia repair by one of two surgeons under local anesthesia
      with sedation were evaluated. Patients were invited to participate in this
      investigation at the time of the preoperative surgical visit. Patients who had a
      contraindication to the use of ketorolac or who refused repair under local
      anesthesia with sedation were excluded. Patients received ketorolac 60 mg either
      via the parenteral route or directly in the surgical site (mixed with the local
      anesthetic). The outcome measures included visual analog pain scores, measured at
      two different times in the hospital, pain scores at rest and with movement 24
      hours after surgery, time to first analgesic, and total analgesic requirement.
      RESULTS: The study revealed lower 24 hour movement-associated pain scores (P <
      .02), increased time to first analgesic (P < .03), and decreased oral analgesic
      consumption (P < .0002) in the surgical site group. CONCLUSIONS: Ketorolac
      provides enhanced patient comfort when it is administered in the surgical site in
      patients undergoing inguinal hernia repair. It is recommended that clinicians add
      ketorolac to the local anesthetic solution in such patients.

PMID- 9168215
TI  - The effect of head-down tilt position on arterial blood pressure after spinal
      anesthesia for cesarean delivery.
AB  - BACKGROUND AND OBJECTIVES: The effect of the head-down tilt position after
      induction of spinal anesthesia for cesarean delivery on blood pressure and level
      of sensory block was examined. METHODS: Patients were allocated randomly into two
      groups, the head-down tilt group (n = 17) and the horizontal group (n = 17). In
      the head-down tilt group, patients were positioned with a 10 degrees head-down
      tilt immediately after supine positioning, while those in the horizontal group
      were maintained in a horizontal position. All patients received 500 mL of
      lactated Ringer's solution intravenously over 10 minutes prior to spinal
      injection, a wedge was placed under the patient's right hip, and the operating
      table was rotated 5 degrees in a counterclockwise direction to provide left
      uterine displacement. Hypotension (defined as systolic blood pressure below 100
      mm Hg) was treated with 5 mg ephedrine intravenously and an increase in the
      infusion rate of lactated Ringer's solution. The change in systolic blood
      pressure was expressed as percent change from the baseline value. RESULTS:
      Systolic blood pressure decreased 20% at 3 minutes after spinal block in both
      groups but recovered to half of this decrease. The incidence of postspinal
      hypotension was not different between the two groups. The total amount of
      ephedrine and lactated Ringer's solution administered during the first 20 minutes
      of spinal block did not differ between the two groups nor did the extent of the
      cephalad spread of analgesia 20 minutes after spinal block (T4 +/- 2 vs T4 +/- 1
      for the head-down and horizontal groups, respectively). CONCLUSIONS: The head
      down position is concluded to have no effect on the incidence of hypotension
      during spinal anesthesia for cesarean delivery.

PMID- 9168216
TI  - Tramadol and beta-cyclodextrin piroxicam: effective multimodal balanced analgesia
      for the intra- and postoperative period.
AB  - BACKGROUND AND OBJECTIVES: This study was conducted to evaluate the analgesic
      efficacy of tramadol, an analgesic with both opioid and nonopioid actions
      (norepinephrine and serotonin pathways), with beta-cyclodextrin piroxicam, a
      nonsteroidal antiinflammatory drug, in the perioperative setting. METHODS: The
      study population consisted of 48 patients scheduled for minor abdominal
      procedures, who were assigned to one of four groups of 12 patients each. The
      premedication was either a placebo tablet or a 192.1-mg beta-cyclodextrin
      piroxicam tablet, administered orally 30-40 minutes before anesthesia induction.
      After intravenous administration of tramadol 1.5 mg/kg, anesthesia was induced
      with an intravenous loading dose of propofol. Anesthesia was maintained an
      intravenous infusion of propofol at 6-12 mg/kg/h plus either saline or tramadol
      at 1.2 mg/kg/h, atracurium, and a 2:1 nitrous oxide-oxygen mixture. The control
      group received a placebo tablet and an infusion of saline with propofol for
      anesthesia maintenance; the tramadol group received a placebo tablet and a
      continuous tramadol-propofol infusion; the beta-cyclodextrin piroxicam (BCP)
      group received a BCP tablet and a continuous saline-propofol infusion; and the
      beta-cyclodextrin piroxicam-tramadol (BCPT) group received beta-cyclodextrin
      piroxicam and a continuous tramadol-propofol infusion. RESULTS: The relative
      propofol consumption by the four groups was control = BCP (P > .05) >tramadol (P
      < .001) > B-CPT (P < .0002). The time for analgesic rescue decreased in the order
      BCPT > BCP (P < .0002) = tramadol > control (P < .001). The degree of sedation
      and the visual analog scores 10-cm scale at the time patients requested rescue
      analgesics were similar among the groups (P > .05). CONCLUSIONS: The combination
      of tramadol and beta-cyclodextrin piroxicam provided better perioperative
      analgesia than tramadol alone.

PMID- 9168217
TI  - Effect of subarachnoid gabapentin on tactile-evoked allodynia in a surgically
      induced neuropathic pain model in the rat.
AB  - BACKGROUND AND OBJECTIVES: Spinal gamma-aminobutyric acid (GABA) receptors have
      been shown to modulate post-nerve injury-induced allodynia. This study sought to
      examine the antiallodynic effects of a GABA analog gabapentin [1
      (aminomethyl)cyclohexaneacetic acid], given by subarachnoid injection in a rat
      neuropathic pain model. METHODS: The rats were prepared with lumbar subarachnoid
      catheters, and allodynia was induced in rats by ligation of the L5-6 nerve roots
      (Chung model). RESULTS: Spinal injection of gabapentin resulted in a dose
      dependent (10-1,000 microg) antagonism of the allodynia at doses that had no
      detectable effect on motor function. Subarachnoid injection of either the GABA A
      antagonist bicuculline (0.3 microg), or the GABA B antagonist CGP 35348 (30
      microg) 5 minutes before or 60 minutes after injection of GABA receptor agonist
      did not reverse the antiallodynic effects produced by gabapentin. CONCLUSIONS:
      Gabapentin shows antiallodynic effect, but its mechanism is not known. The
      failure to reverse this effect by GABA A or B antagonists at doses that reverse
      the effects of the respective agonists suggests that gabapentin is involved in
      the modulation of spinal systems by mechanisms that do not involve either a GABA
      A or a GABA B site.

PMID- 9168218
TI  - Thermal grill illusion and complex regional pain syndrome type I (reflex
      sympathetic dystrophy).
AB  - BACKGROUND AND OBJECTIVES: In normal humans, placing a hand on a thermal grill
      containing warm elements separated by cool ones produces a burning sensation. In
      this case report, responses to a thermal grill in a patient with neuropathic pain
      were examined. METHODS: The responses of a 31-year-old woman with complex
      regional pain syndrome type I (reflex sympathetic dystrophy) to a thermal grill
      were evaluated before and after stellate ganglion block. RESULTS: The patient
      experienced a burning sensation when the unaffected hand was placed on the grill
      and could distinguish which element was warm and which was cool. An intolerable
      burning sensation caused the patient to quickly (within 4 seconds) withdraw the
      affected hand when it was placed on the grill. Touching cool elements with the
      affected hand produced an intense burning sensation (cold allodynia), whereas
      touching warm elements produced a pleasant warm sensation. Stellate ganglion
      block with phenol, local anesthetic, and steroid resulted in long-lasting absence
      of cold allodynia. CONCLUSION: The thermal grill may be a useful a tool to help
      understand the pathophysiology of complex regional pain syndrome type I.

PMID- 9168219
TI  - Comparison of accuracy and cost of disposable, nonmechanical pumps used for
      epidural infusions.
AB  - BACKGROUND AND OBJECTIVES: Temporary epidural catheter pumps are used to infuse
      analgesics in patients with chronic intractable pain. Three brands of disposable,
      nonmechanical pumps adapted for epidural infusion were tested to determine their
      flow rate efficacy and their cost effectiveness. METHODS: Three pump models were
      tested: the Baxter (2C1075), Homepump (H100020), and SurgiPEACE (SP500-24).
      Manufacturers of each unit claim to provide a constant 2-mL/h flow rate. A
      standard setup was used to simulate both the insertion of the catheter into the
      epidural space and the environmental conditions consistent with patient
      ambulation. Reservoirs were filled with water and allowed to infuse into a
      collection receptacle, and flow rates were measured hourly. Four trials were
      performed with four separate units and flow rate measurements were averaged to
      determine a flow rate pattern over the entire infusion period. Data were graphed
      as the percentage of expected flow rate (% of 2 mL/h) versus infusion time
      (hours), the 90-110% range being defined as acceptable. RESULTS: All pumps
      initially infused at a rate above 110% for the first 3-6 hours, after which a
      steady decline in flow rate was observed. The Homepump produced a flow rate in
      the acceptable range for the greatest part of its infusion period (41%), followed
      by the SurgiPEACE (34%), and the Baxter unit (10.4%). The Baxter unit was also
      cumbersome to handle and therefore difficult to fill. The Homepump unit was
      easily handled but offered considerable resistance to filling, with partial loss
      of fluid. The SurgiPEACE unit was easy to handle and fill; however, in two of the
      units tested, an initial blockage was encountered, and manual patency of the
      connector and/or catheter had to be established. CONCLUSIONS: All three units
      deviated considerably from the claimed flow rate of 2-mL/h, both at the beginning
      and at the end of the infusion. Presumably, the decreasing flow rates are
      responsible for the diminishing pain relief often experienced by patients over
      the course of the infusion. The Homepump unit appeared to be the most cost
      effective and the easiest to handle and maintained an acceptable infusion rate
      for the greatest percentage of the infusion period. The considerable cost benefit
      of using a nonmechanical disposable pump as opposed to a costly but more reliable
      computerized pump appears to warrant further product improvement and development.

PMID- 9168220
TI  - Bevel direction, dura geometry, and hole size in membrane puncture: laboratory
      report.
AB  - BACKGROUND AND OBJECTIVES: The cylindrical shape of the dura in vivo, as well as
      the needle tip deviation known to occur with beveled needle insertion, might
      predispose to geometric effects of needle orientation on hole size and shape
      during dural puncture. The object of this study was to investigate such possible
      effects. METHODS: Standard xerographic paper was used to simulate a dura mater
      membrane with random fiber orientation. Rigidly mounted paper cylinders of 2-cm
      diameter were transfixed at 90 degrees angles to the cylinder axis with 22-gauge
      Quincke point spinal needles. A nonrotating drill press effected linear
      insertion, creating entry and exit perforations at median and paramedian
      positions. The bevel direction was rotated at 90 degrees angles during punctures
      in order to determine the effects of lateral versus transverse bevel orientation
      (relative to the cylinder axis) on the resultant hole morphology. RESULTS: With
      median perforation, all holes (entry and exit) were of uniform size and shape
      regardless of bevel orientation. Paramedian perforations of the cylinder at near
      tangential positions, with the bevel directed lateral to the cylinder axis,
      resulted in formation of a flap overlapping the margins of either the entry or
      exit hole but not both. Flaps formed only when the bevel faced the cylinder
      membrane's surface during paramedian, near tangential puncture (n = 10, P =
      .00001). CONCLUSIONS: The geometric interactions of membranes with Quincke
      needles lend support to the practice of needle insertion with the bevel facing
      laterally in order to produce smaller holes. Geometry may help to explain the
      reduced rate of postdural puncture headache found with Quincke bevels oriented to
      face laterally during midline approach and during paramedian technique,
      particularly when a single puncture results in aspiration of cerebrospinal fluid.

PMID- 9168221
TI  - Emery A. Rovenstine and regional anesthesia.
AB  - BACKGROUND AND OBJECTIVES: Emery Andrew Rovenstine was a dominant figure in
      anesthesiology in the United States between 1935 and 1960. Among his many
      contributions to the specialty, his regional anesthesia practice remains less
      well known. This paper explores Rovenstine's career and his contributions to
      regional anesthesia. METHODS: Original documents studied and classified for this
      investigation included all of Rovenstine's published papers and the extant
      documents of the original American Society of Regional Anesthesia. Interviews
      with several physicians who knew Rovenstine were conducted. Secondary source
      materials, including biographies of Rovenstine, were perused. RESULTS: Rovenstine
      made a major contribution to regional anesthesia through patient care, teaching,
      and political action. Many of his students went on to become leaders in
      anesthesiology and emphasized regional anesthesia in the second half of the
      twentieth century. CONCLUSIONS: Emery A. Rovenstine did much to popularize
      regional anesthesia and ensure a rightful place for its techniques within the
      armamentarium of the anesthesiologist. Keeping alive the traditions of Gaston
      Labat at Bellevue, Rovenstine's contributions to regional anesthesia on all
      levels were considerable. Most importantly, he ensured an enduring role for
      regional anesthesia through the recurring contributions of his pupils.

PMID- 9168223
TI  - Stellate ganglion block alleviates pseudo-obstruction symptoms followed by
      episodes of hypermetropia: case report.
AB  - BACKGROUND AND OBJECTIVES: The chronic intestinal pseudo-obstruction due to
      visceral myopathy is a disorder resembling bowel obstruction but without
      mechanical occlusion. Frequently, parenteral nutrition becomes the final
      palliative treatment. A patient affected with this syndrome for 16 years was
      suffering causalgic pain provoked by intraveneous perfusion. Stellate ganglion
      block was requested in the hope of maintaining the perfusion. METHODS: Stellate
      ganglion block not only stopped the pain but unexpectedly, it temporarily
      relieved the pseudo-obstruction symptoms. Two radiofrequency coagulations in the
      stellate ganglion prolonged the beneficial effects on gastrointestinal transit
      for more than 3 weeks, after which the symptoms returned. Multidisciplinary and
      multicenter advice was that further destructive treatments not be attempted.
      RESULTS: Repetitive stellate ganglion blocks with 2 mL of bupivacaine 0.75%
      restored gastrointestinal function for more than 3 weeks. However, after
      performance of radiofrequency coagulation, infiltration with bupivacaine was
      followed by hypermetropia on the right eye of 2 weeks duration. CONCLUSIONS: The
      relationship between stellate ganglion block and gastrointestinal function has
      not been described. This case report does not provide sufficient information to
      recommend this technique for pseudo-obstruction symptoms. Moreover, the result in
      this case is a fortuitous observation, lacking a clear scientific explanation.
      Further study may be warranted.

PMID- 9168222
TI  - Anesthesia for cesarean delivery in a patient with Ehlers-Danlos syndrome type
      II.
AB  - BACKGROUND AND OBJECTIVES: Ehlers-Danlos syndrome, an inherited connective tissue
      disease, is rarely seen in pregnancy. Presentation may be mild or severe,
      depending on which type of the syndrome the patient possesses. METHODS: A 38-year
      old woman with Ehlers-Danlos syndrome type II presented for cesarean delivery at
      34 weeks' gestation with premature rupture of membranes and breech presentation.
      RESULTS: A subarachnoid block was chosen to provide surgical anesthesia. No
      adverse side effects or complications developed. CONCLUSION: In patients with
      Ehlers-Danlos syndrome, it is important to be aware of which type is present and
      to be knowledgeable about and prepared for any potential complications.

PMID- 9168224
TI  - Phantom pain with probable reflex sympathetic dystrophy: efficacy of fentanyl
      infiltration of the stellate ganglion.
AB  - BACKGROUND AND OBJECTIVES: The stellate ganglion can alleviate phantom pain of
      the upper extremity, possibly because of the presence in it of enkephalin
      receptors, as has been suggested by experimental and clinical reports. A case is
      reported in which fentanyl, instead of local anesthetic, was used for stellate
      ganglion block. METHODS: A 49-year-old man, with a left below-elbow amputation,
      presented with probable symptoms of reflex sympathetic dystrophy, pain and
      temperature changes at the stump, and phantom hand symptoms the English-language
      literature revealed no reports of the use of fentanyl infiltration of the
      stellate ganglion was performed for management of this condition. RESULTS:
      Significant alleviation of pain and sensation of warmth at the stump and in the
      phantom hand was achieved. CONCLUSIONS: Fentanyl infiltration of the stellate
      ganglion proved to be successful in the management of the pain and temperature
      sensation changes in the stump and phantom upper extremity.

PMID- 9168225
TI  - Nalmefene, an intravenous alternative to naltrexone for extradural morphine
      prophylaxis.

PMID- 9168226
TI  - Children do experience phantom limb pain.

PMID- 9168227
TI  - A simplified maneuver for transarterial approach to axillary block for use by a
      single anesthesiologist--needs more explanation!

PMID- 9168228
TI  - The evolution of combined spinal-epidural anesthesia needles.

PMID- 9168229
TI  - A new type of spinal introducer.

PMID- 9168230
TI  - How to reduce the risk for contamination of the central nervous system by spinal
      needles.

PMID- 9168231
TI  - Comments on posterior epidural space depth measurement.

PMID- 9168233
TI  - Synergistic neutralization of a chimeric SIV/HIV type 1 virus with combinations
      of human anti-HIV type 1 envelope monoclonal antibodies or hyperimmune globulins.
AB  - A panel of 14 human IgG monoclonal antibodies (MAbs) specific for envelope
      antigens of the human immunodeficiency virus type 1 (HIV-1), 2 high-titer human
      anti-HIV-1 immunoglobulin (HIVIG) preparations, and 15 combinations of MAbs or
      MAb/HIVIG were tested for their ability to neutralize infection of cultured human
      T cells (MT-2) with a chimeric simian immunodeficiency virus (SHIV-vpu+), which
      expressed HIV-1 IIIB envelope antigens. Eleven MAbs and both HIVIGs were
      neutralizing. When used alone, the anti-CD4-binding site MAb b12, the anti-gp41
      MAb 2F5, and the anti-gp120 MAb 2G12 were the most potent. When combination
      regimens involving two MAbs targeting different epitopes were tested, synergy was
      seen in all paired MAbs, except for one combination that revealed additive
      effects. The lowest effective antibody concentration for 50% viral neutralization
      (EC50) and EC90 were achieved with combinations of MAbs b12, 2F5, 2G12, and the
      anti-V3 MAb 694/98D. Depending on the combination regimen, the concentration of
      MAbs required to reach 90% virus neutralization was reduced approximately 2- to
      25-fold as compared to the dose requirement of individual MAbs to produce the
      same effect. Synergy of the combination regimens implies that combinations of
      antibodies may have a role in passive immunoprophylaxis against HIV-1. The
      ability of SHIV to replicate in rhesus macaques will allow us to test such
      approaches in vivo.

PMID- 9168235
TI  - Basolateral sorting of the HIV type 2 and SIV envelope glycoproteins in polarized
      epithelial cells: role of the cytoplasmic domain.
AB  - In polarized epithelial cell lines, enveloped viruses are directionally released
      by asymmetric viral budding at specific plasma membrane domains. Previous studies
      have shown that HIV-1 budding and gp160 expression occur on basolateral membranes
      whereas the release of HIV-1 Gag particles, in the absence of the Env
      glycoproteins, is nonpolarized. We have examined the directional transport and
      surface expression of HIV-2 and SIV envelope glycoproteins using vaccinia virus
      recombinants in Vero C1008 polarized epithelial cells. Analogous to HIV-1 gp160,
      both HIV-2 and SIV surface glycoproteins were preferentially directed to
      basolateral membranes. Hence basolateral expression appears to be a common
      property of the glycoproteins of primate lentiviruses. To explore the role of the
      cytoplasmic domain in directing the HIV-2 and SIV Env glycoproteins to the
      basolateral surface, stop codons were introduced to mimic the natural cytoplasmic
      truncations observed following repeated passage of these viruses in culture.
      These truncated glycoproteins also were sorted to the basolateral domain, but at
      a lower efficiency than the full-length protein product. In contrast, when the
      entire cytoplasmic domain of the SIV Env glycoprotein was deleted, the tailless
      SIV mutant was preferentially expressed on the apical surface. These data
      indicate the presence of a basolateral sorting signal in the cytoplasmic domain
      of primate lentiviral glycoproteins.

PMID- 9168236
TI  - The in vitro anti-HIV efficacy of negatively charged human serum albumin is
      antagonized by heparin.
AB  - Succinylated human serum albumin (Suc-HSA) was synthesized by treating human
      serum albumin with succinic anhydride. Among similar proteins and
      neo(glyco)proteins tested, Suc-HSA exhibits a pronounced net negative charge, a
      feature that largely contributes to its efficacy against replication of human
      immunodeficiency virus type 1 (HIV-1). To assess further the antiviral effect of
      Suc-HSA, the effect on HIV-1 replication was studied in the presence of whole
      human plasma. Pretreatment of MT2 cells with Suc-HSA was more efficacious than
      direct Suc-HSA treatment of HIV prior to addition to the cells. No changes in the
      antiviral effect of Suc-HSA were observed in tissue culture medium, 30% plasma,
      or whole plasma when CPDA-1 (citrate-phosphate-dextrose-adenine 1) was used as
      the anticoagulant. However, a dramatic decrease (greater than 99%) in the
      antiviral activity was observed when these experiments were performed in plasma
      prepared from blood using heparin as anticoagulant. The antagonistic effect by
      heparin was observed both in the case that heparin was added prior to or after
      addition of Suc-HSA to the test system. In the present study we demonstrate that
      heparin largely reduces Suc-HSA activity on HIV replication in the same
      concentration in which if affects binding of Suc-HSA to the envelope protein
      gp120 and in particular its V3 domain. In the same concentration range, heparin
      reduced binding of Suc-HSA to MT4 cells, another HTLV-I-transformed cell line. It
      is concluded that heparin can displace Suc-HSA from its binding sites on hybrid
      lymphoid cells as well as on HIV-1 particles. Therefore, we conclude that both
      the binding to cells and to virus contribute to the potent anti-HIV-1 effect. The
      fact that heparin and heparin degradation products antagonize Suc-HSA without
      having a significant anti-HIV-1 effect indicates that the anticoagulant acts as a
      relatively weak partial inhibitor.

PMID- 9168232
TI  - Characterization of the pathogenic KU-SHIV model of acquired immunodeficiency
      syndrome in macaques.
AB  - By animal-to-animal passage in macaques we derived a pathogenic chimeric simian
      human immunodeficiency virus (SHIV) that caused CD4+ T cell loss and AIDS in
      pigtail macaques and used it to inoculate 20 rhesus and pigtail macaques by the
      intravaginal and intravenous routes. On the basis of the outcome of infection and
      patterns of CD4+ T cell loss and viral load, disease was classified into four
      patterns: acute, subacute, chronic, and nonprogressive infection. During the
      study period, 15 of the 20 animals developed fatal disease, including AIDS,
      encephalitis, pneumonia, and severe anemia. Opportunistic pathogens identified in
      these animals included Pneumocystis, cytomegalovirus, Cryptosporidium,
      Toxoplasma, and Candida. No single parameter by itself predicted outcome,
      although a combination of low CD4+ T cell counts in blood, high plasma virus
      levels, and presence of autoantibodies to red blood cells reliably predicted a
      fatal outcome. Five animals (25%) died within 3 months of inoculation and
      constituted the group with acute disease, whereas the nine animals (45%) with
      subacute disease died between 3 and 8 months postinoculation. This 70% mortality
      within 8 months is significantly shorter than in HIV-1-infected human beings, of
      whom 70% develop fatal disease a decade after infection. SHIV infection in
      macaques provides a useful model with which to evaluate antiviral strategies,
      combining all the advantages of the SIVmac system, yet using a virus bearing the
      envelope gene of HIV-1.

PMID- 9168234
TI  - Identification of a synthetic peptide that mimics an HIV glycoprotein 120
      envelope conformational determinant exposed following ligation of glycoprotein
      120 by CD4.
AB  - CD4 ligation of HIV envelope gp120 results in conformational changes in gp120
      that lead to exposure of the gp41 fusogenic domain and fusion with the host cell
      membrane. One determinant at or near the CD4-binding site exposed on gp120
      subsequent to CD4 binding is defined by two human MAbs termed 17b and 48d. These
      MAbs do not block CD4 binding to gp120; rather, their binding to gp120 is
      upregulated following CD4 binding. To determine if synthetic peptide mimetopes
      could be found that reflect conformational determinants on the surface of gp120,
      synthetic gp120 peptides from 10 divergent HIV isolates were screened for their
      ability to bind to 17b and 48d in ELISAs. Although MAb 48d binds to HIV IIIB
      recombinant gp120 protein, in our studies 48d selectively bound only to the HIV
      Can0A V3 peptide and not to HIV IIIB V3 peptide, whereas MAb 17b bound none of
      the peptides tested. Monoclonal antibody 48d bound to the HIV Can0A V3 peptide
      both in solid-phase ELISA and in solution in a competitive ELISA, but could not
      bind to HIV Can0A V3 peptide bound to human T cells. The HIV Can0A V3 peptide
      induced anti-HIV antibodies in rhesus monkeys that neutralized the laboratory
      adapted HIV MN strain but did not induce antibodies that neutralized HIV
      IIIB/LAI, HIV SF-2, or HIV RF isolates, or that neutralized HIV primary isolates.
      These data suggested that the primary sequence of the HIV Can0A V3 loop exists in
      a conformer that mimicks a non-V3 determinant of native gp120 exposed subsequent
      to CD4 binding on the surface of gp120 of laboratory-adapted HIV strains.
      Structural studies of the Can0A V3 peptide and/or the 48d MAb may provide
      important information regarding the nature of gp120 conformational changes that
      occur following gp120 ligation by CD4.

PMID- 9168237
TI  - Analysis of CD8+ T lymphocyte-mediated nonlytic suppression of autologous and
      heterologous primary human immunodeficiency virus type 1 isolates.
AB  - Nonlytic CD8+ T lymphocyte antiviral factor (CAF) activity has been described as
      having an important role in the clinical course of human immunodeficiency virus
      type 1 (HIV-1) infection. Testing of CAF activity against autologous viruses
      isolated at approximately the same time points showed that CD8+ T lymphocytes
      from long-term survivors indeed possessed high CAF activity. However, in four of
      six progressors to AIDS, we observed the same amount of CAF activity in the face
      of increasing cellular HIV-1 load. In the other two progressors, CAF activity
      seemed preserved over time whereas the susceptibility of the virus isolate
      obtained late in infection seemed to be diminished. In a heterologous system, CAF
      activity of CD8+ T lymphocytes from 13 HIV-1-positive individuals did not
      correlate with CD4+ T lymphocyte counts. In two of three patients, syncytium
      inducing (SI) HIV-1 variants, which are associated with a progressive clinical
      course, appeared to have a somewhat reduced susceptibility to CAF activity as
      compared to their coexisting non-SI HIV-1 variants. In a large donor group,
      suppression of SI isolates (as compared to non-SI isolates) mediated by
      heterologous CD8+ T lymphocytes was reduced. CD8+ T lymphocytes from five of six
      HIV-1-positive individuals suppressed HIV-1 replication in macrophages. CD8+ T
      lymphocytes from noninfected donors, even from cord blood, already had high CAF
      activity, suggesting that induction of this activity is neither virus nor HIV-1
      specific.

PMID- 9168238
TI  - Tetrahydronaphthalene lignan compounds as potent anti-HIV type 1 agents.
AB  - Anti-HIV-1 activity of tetrahydronaphthalene (THN) derivatives of lignan
      compounds was studied. THN derivatives prevented cell death caused by HIV-1
      infection in MT-4 cells. They also inhibited giant cell formation by HIV-1 in Sup
      T1 cells, and p24 production in HIV-1-infected H9 cells. The 50% effective
      concentration (ED50) of the most active compound, 1737 [5,6,7-trimethoxy-4-(3,4,5
      trimethoxyphenyl)-1,3,3a,4,9,9a-hexahydron aphtho[2,3-c]thiophene], for
      inhibition of the cytopathic effects of HIV-1 infection ranged from 0.15 to 0.8
      microM. The 50% cytotoxic concentration (CC50) of compound 1737 measured by the
      viability of MT-4 cells was 58 microM, indicating a selective index (CC50/ED50)
      of 70-400. Substitution of the phenyl ring with other structures markedly
      decreased cytotoxicity but did not affect the antiviral activity of the
      compounds. This resulted in compounds with a high selective index. One such
      compound was 1738 [7-methoxy5,6-methylenedioxy-4-(4-benzyloxy-3
      methoxyphenyl)1,3,3a ,4,9,9a-hexahydronaphtho[2,3-c]thiophene], with a selective
      index higher than 770. The time-of-addition experiment indicated that these
      compounds acted at or near the reverse transcription step of the HIV-1 life
      cycle. THN derivatives inhibited HIV-1 reverse transcriptase (RT) in vitro at a
      concentration of 1 microM. Resistant viruses selected in the presence of THN
      derivatives showed some degree of cross-resistance to other nonnucleoside RT
      inhibitors, but not to the nucleoside RT inhibitor, AZT. THN derivatives failed
      to inhibit replication of pyridinone- and nevirapine-resistant HIV strains.
      However, compound 1737 inhibited replication of a TIBO-resistant strain more
      effectively than the wild-type HIV-1. Consistent with this result, compound 1737
      also inhibited TIBO-resistant RT more effectively than the wild-type RT in vitro.
      These results suggested that THN derivatives interact with RT in a manner similar
      to but slightly different from that of other nonnucleoside HIV-1 RT inhibitors.

PMID- 9168239
TI  - Effects of (R)-9-(2-phosphonylmethoxypropyl)adenine monotherapy on chronic SIV
      infection in macaques.
AB  - (R)-9-(2-Phosphonylmethoxypropyl)adenine (PMPA) acts as a reverse transcriptase
      inhibitor of retroviruses and has been shown to be effective against acute simian
      immunodeficiency virus (SIV) infection in macaques. To study its efficacy at
      different stages of infection, we tested PMPA in cynomolgus macaques (Macaca
      fascicularis) that had been chronically infected with SIVMne for at least 19
      weeks before treatment was begun. PMPA was administered subcutaneously in a
      single daily dose of either 30 or 75 mg/kg body weight for 28 days. Within < or =
      2 weeks of treatment, PMPA in both dosing regimens reduced SIV levels by >99% in
      the plasma or peripheral blood mononuclear cells; in some macaques SIV levels
      were reduced to below the lower quantitation limit. At a dose of 30 mg/kg/day
      PMPA was well tolerated, causing no side effects while increasing the mean CD4+
      cell counts in animals that received this dose. Thus PMPA seems to be a promising
      agent for use against retroviral infections.

PMID- 9168240
TI  - Regression of feline immunodeficiency virus infection.
AB  - Regression of feline immunodeficiency virus (FIV) infection was observed in seven
      of nine vertically infected kittens born to two chronically infected mother cats.
      Both provirus and nonmaternal FIV antibody were detected in all kittens by 4
      weeks of age but only three of the seven kittens were positive by blood
      mononuclear cell coculture. Between 10 and 14 months of age blood mononuclear
      cells from each of the seven cats were negative at least once by polymerase chain
      reaction (PCR), but evidence of virus infection was detected by coculture and/or
      PCR in biopsied lymph node or bone marrow from five of the seven cats. Despite
      this evidence of persistent tissue provirus, antibody production did not persist
      in any of the cats beyond 1 year of age. All seven cats remained asymptomatic
      although CD4 and CD8 T cell counts were in the low normal range throughout the
      study. By contrast, two additional perinatally infected littermates that were
      persistently virus isolation positive developed rapid CD4 depletion and
      progressed to terminal immunodeficiency by 9 weeks of age. Thus FIV infection can
      be downregulated and/or sequestered to extremely low levels barely detectable
      with the assays available, although absolute clearance of virus may not occur.
      These observations are relevant to human immunodeficiency virus (HIV) infection
      in paralleling both the apparent "regression" of HIV infection reported in some
      perinatally infected infants and the low-level, apparently stable, infection
      established by attenuated simian immunodeficiency viruses.

PMID- 9168241
TI  - DNA sequence analysis of the long terminal repeat of the C subtype of human
      immunodeficiency virus type 1 from Southern Africa reveals a dichotomy between B
      subtype and African subtypes on the basis of upstream NF-IL6 motif.

PMID- 9168242
TI  - HIV type 1 subtype E in Russia.

PMID- 9168243
TI  - RNA and DNA sequence analysis of the nef gene of HIV type 1 strains from the
      first HIV type 1-infected long-term nonprogressing mother-child pair.

PMID- 9168244
TI  - Free radical mechanisms of neurotoxicity.

PMID- 9168245
TI  - Reactive oxygen-mediated protein oxidation in aging and disease.

PMID- 9168246
TI  - beta-Amyloid-associated free radical oxidative stress and neurotoxicity:
      implications for Alzheimer's disease.

PMID- 9168247
TI  - Disruption of brain cell ion homeostasis in Alzheimer's disease by oxy radicals,
      and signaling pathways that protect therefrom.

PMID- 9168248
TI  - Mechanisms of neurotoxicity associated with amyloid beta deposition and the role
      of free radicals in the pathogenesis of Alzheimer's disease: a critical
      appraisal.

PMID- 9168249
TI  - Nitric oxide and derived species as toxic agents in stroke, AIDS dementia, and
      chronic neurodegenerative disorders.

PMID- 9168250
TI  - Microprobe X-ray absorption spectroscopic determination of the oxidation state of
      intracellular chromium following exposure of V79 Chinese hamster lung cells to
      genotoxic chromium complexes.
AB  - The oxidation state of intracellular chromium has been determined directly in
      mammalian lung cells exposed to mutagenic and carcinogenic chromium compounds.
      Microprobe X-ray absorption spectroscopy (XAS) experiments on single V79 Chinese
      hamster lung cells showed that Cr(VI) and Cr(V) complexes were reduced completely
      (>90%) to Cr(III) within 4 h of exposure of the cells. This result provides
      direct evidence for the hypothesis that these genotoxic oxidants react rapidly
      with intracellular reductants.

PMID- 9168251
TI  - Levuglandin E2-protein adducts in human plasma and vasculature.
AB  - The prostaglandin endoperoxide PGH2 rearranges nonenzymatically to generate
      prostaglandins and secoprostanoic acid levulinaldehyde derivatives such as PGE2
      and levuglandin (LG) E2, respectively. Direct detection of LGE2 in biological
      samples is complicated because it is rapidly sequestered by covalent adduction to
      endogenous nucleophiles including proteins, which produces LGE2-derived protein
      bound pyrroles. Therefore, to detect LGE2-protein adducts in vivo, antibodies
      were raised against a covalent adduct of LGE2 with keyhole limpet hemocyanin
      (KLH). This antigen enabled the production of high-titer antibodies that exhibit
      minimal cross-specificity and are sensitive for detecting LGE2-derived pyrroles.
      Although pyrrole yields are low at LG/protein ratios found in vivo, an enzyme
      linked immunosorbent assay with the LGE2-KLH antibodies detects LGE2-derived
      protein-bound pyrrole immunoreactivity in human plasma from specific patient
      populations. Furthermore, prominent immunocytochemical staining of human brain
      thin sections revealed the presence of LGE2-derived pyrrole immunoreactivity,
      especially in the meningeal vessels of some patients. This demonstration of LG
      protein adducts in human plasma and vasculature provides the first evidence for
      the biological occurrence of levuglandins in vivo and further suggests that these
      antibodies might prove useful in diagnostic and mechanistic studies of various
      disease conditions.

PMID- 9168253
TI  - Temperature-dependent formation of a conjugate between
      tris(hydroxymethyl)aminomethane buffer and the malondialdehyde-DNA adduct
      pyrimidopurinone.
AB  - The stability of the major adduct formed between the endogenous product
      malondialdehyde (MDA) and deoxyguanosine, a pyrimidopurinone termed M1G-dR, was
      tested under a variety of conditions required for nucleic acid manipulation. M1G
      dR was found to be stable at neutral pH and 37 degrees C but to be unstable when
      stored at -20 degrees C in the presence of Tris buffers. A new product with a
      characteristic absorption band at 350 nm was identified by 1H-NMR as an enamino
      imine comprised of one molecule of Tris, one molecule of MDA, and deoxyguanosine.
      The formation of the conjugate was observed on reaction of Tris with M1G-dR or
      its ring-opened derivative N2-(3-oxo-1-propenyl)deoxyguanosine. The Tris-M1G-dR
      conjugate was unstable in aqueous solutions at room temperature, undergoing
      hydrolysis. However, the Tris conjugate of M1G base remained stable at room
      temperature in organic solvent. The isolation and properties of a conjugate
      between M1G-dR and Tris suggest that cross-links may form by reaction of MDA with
      DNA but they are likely to be unstable to hydrolysis.

PMID- 9168252
TI  - Immunochemical identification of mouse hepatic protein adducts derived from the
      nonsteroidal anti-inflammatory drugs diclofenac, sulindac, and ibuprofen.
AB  - Reactive metabolite-modified hepatic protein adducts have been proposed to play
      important roles in the mechanism(s) of hepatotoxicity of nonsteroidal anti
      inflammatory drugs (NSAIDs). In the present study, immunochemical techniques have
      been used to compare the patterns of drug-protein adducts expressed in livers of
      mice given single doses of one or other of three different NSAIDs. These were
      diclofenac and sulindac, which are widely used but potentially hepatotoxic drugs,
      and ibuprofen, which is considered to be nonhepatotoxic. Specific polyclonal
      antisera were produced by immunization of rabbits with conjugates prepared by
      coupling each of the NSAIDs to the carrier protein keyhole limpet hemocyanin.
      Immunoblotting studies revealed dose-dependent formation of major 110 kDa
      polypeptide adducts in livers from mice sacrificed 6 h after administration of
      single doses of either diclofenac (0-300 mg/kg) or sulindac (0-100 mg/kg). Lower
      levels of several other adducts, of 140 and 200 kDa, were also expressed in
      livers from these animals. In contrast, livers from mice treated with ibuprofen
      (0-200 mg/kg) predominantly expressed a 60 kDa adduct and only relatively low
      levels of a 110 kDa adduct. The various adducts were shown by differential
      centrifugation to be concentrated in the nuclear fraction of liver homogenates.
      Those derived from diclofenac and sulindac were further localized, by Percoll
      density gradient centrifugation, to a subfraction which contained a high activity
      of the bile canalicular marker enzyme alkaline phosphatase. This suggests that
      they are concentrated in the bile canalicular domain of hepatocytes. The
      different patterns of adduct formation raise the possibility that formation of
      certain NSAID protein adducts, particularly 110 kDa adducts, has toxicological
      significance.

PMID- 9168254
TI  - Pyridyloxobutyl adduct O6-[4-oxo-4-(3-pyridyl)butyl]guanine is present in 4
      (acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone-treated DNA and is a
      substrate for O6-alkylguanine-DNA alkyltransferase.
AB  - The lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is
      activated to reactive metabolites that methylate or pyridyloxobutylate DNA.
      Previous studies demonstrated that pyridyloxobutylated DNA interferes with the
      repair of O6-methylguanine (O6-mG) by O6-alkylguanine-DNA alkyltransferase (AGT).
      The AGT reactivity of pyridyloxobutylated DNA was attributed to
      (pyridyloxobutyl)guanine adducts. One potential AGT substrate adduct, 2'-deoxy-O6
      [4-oxo-4-(3-pyridyl)butyl]guanosine (O6-pobdG), was prepared. This adduct was
      stable at pH 7.0 for greater than 13 days and to neutral thermal hydrolysis
      conditions (pH 7.0, 100 degrees C, 30 min). Under mild acid hydrolysis conditions
      (0.1 N HCl, 80 degrees C), O6-pobdG was depurinated to yield O6-[4-oxo-4-(3
      pyridyl)butyl]guanine (O6-pobG). O6-pobdG was hydrolyzed to 4-hydroxy-1-(3
      pyridyl)-1-butanone and guanine under strong acid hydrolysis conditions (0.8 N
      HCl, 80 degrees C). O6-pobG was detected in 0.1 N HCl hydrolysates of DNA
      alkylated with the model pyridyloxobutylating agent 4-(acetoxymethylnitrosamino)
      1-(3-[5-3H]pyridyl)-1-butanone ([5-3H]NNKOAc). When [5-3H]NNKOAc-treated DNA was
      incubated with either rat liver or recombinant human AGT, O6-pobG was removed,
      presumably a result of transfer of the pyridyloxobutyl group from the O6-position
      of guanine to AGT's active site.

PMID- 9168255
TI  - Frameshift mutagenesis induced in Escherichia coli after in vitro treatment of
      double-stranded DNA with methylene blue plus white light: evidence for the
      involvement of lesion(s) other than 8-oxo-7,8-dihydro-2'-deoxyguanosine.
AB  - By means of specific mutation assays, we show here that in vitro treatment of
      double-stranded plasmid DNA with methylene blue and white light efficiently
      promotes frameshift mutagenesis in Escherichia coli. The assays detect either -1
      or -2 frameshift mutations within previously characterized hot spot sequences for
      frameshift mutagenesis induced by the chemical carcinogen N-2
      acetylaminofluorene, namely, short runs of contiguous guanines and alternating
      GpC sequences, respectively. The SOS and umuDC dependences of these mutagenic
      processes have been investigated. Both -1 and -2 frameshift mutagenesis are
      increased when the host SOS functions are induced. However, and although
      functional UmuDC proteins are required for maximal mutation induction, the
      inducibility of both -1 and -2 frameshift mutagenesis is partially independent
      upon the integrity of the umuDC operon. In addition, results obtained using
      plasmids with a site specifically located 7,8-dihydro-8-oxo-2'-deoxyguanosine (8
      oxo-dGuo) residue show that this lesion, the major methylene blue plus light
      induced lesion characterized so far, is inefficient in promoting frameshift
      mutagenesis. Together, these results led us to conclude that methylene blue plus
      light treatment of DNA induces, at relatively high rates, lesion(s) other than 8
      oxo-dGuo, that efficiently promote(s) frameshift mutagenesis in E. coli.

PMID- 9168256
TI  - Role of G-->T transversions in the mutagenicity of alkylperoxyl radicals:
      induction of alkali-labile sites in bacteriophage M13mp19.
AB  - The mutagenicity of peroxyl radicals, ubiquitous products of lipid peroxidation,
      was assessed using an in vitro M13 forward mutational assay. Single-stranded
      M13mp19 plasmids were incubated with a range of concentrations of the azo
      initiator 2,2'-azobis(2-amidinopropane) hydrochloride, and then transfected into
      competent, SOS-induced Escherichia coli JM105 cells. Incubation with peroxyl
      radicals produced a concentration-dependent decrease in phage survival, with a
      500 microM concentration of the azo initiator reducing the transfection
      efficiency by more than 90% while inducing a corresponding 6-fold increase in
      lacZ alpha mutation frequencies. Peroxyl radical-induced mutagenesis was
      completely prevented by the peroxyl radical scavenger Trolox. Automated DNA
      sequence analysis of the lacZ alpha gene of 100 peroxyl radical-induced mutants
      revealed that the most frequent sequence changes were base pair substitutions
      (92/95), with G-->T transversions predominating (73/92). Alkaline treatment prior
      to transfection diminished the mutagenicity of damaged plasmids to a level
      resembling that of unmodified DNA. While abasic sites might account for the
      sensitivity to alkaline cleavage, the possibility that unidentified nonabasic
      alkaline-labile lesions also contribute to peroxyl radical mutagenesis cannot be
      excluded. Collectively, these findings raise the possibility that DNA damage
      caused by a major class of endogenous radicals contributes to one of the most
      common spontaneous mutational events, the G-->T transversion.

PMID- 9168257
TI  - Hydrogen peroxide supports human and rat cytochrome P450 1A2-catalyzed 2-amino-3
      methylimidazo[4,5-f]quinoline bioactivation to mutagenic metabolites:
      significance of cytochrome P450 peroxygenase.
AB  - We show that the naturally occurring hydroperoxide hydrogen peroxide is highly
      effective in supporting the cytochrome P450 1A2 peroxygenase-catalyzed metabolic
      activation of the heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5
      f]quinoline (IQ) to genotoxic metabolites. Mutagenicity was assessed by the Ames
      assay with Salmonella typhimurium strain YG1012 and an activation system
      consisting of hydroperoxides plus either 3-methylcholanthrene-induced rat liver
      microsomes (rP4501A) or human P450 1A2-containing microsomes (hP4501A2). The
      mutagenic response was dependent on the concentration of microsomal protein, IQ,
      and hydroperoxides. The addition of hydrogen peroxide or tert-butyl hydroperoxide
      to rP4501A greatly enhanced the yield of histidine prototrophic (His+)
      revertants. This increase was inhibited, in a concentration-dependent manner, by
      alpha-naphthoflavone, a P450 1A inhibitor. Hydrogen peroxide was the most
      effective peroxygenase cofactor, particularly with hP4501A2 (K(m) = 0.1 mM). The
      hydroperoxide-supported activation of IQ produced reactive intermediates which
      bound to 2'-deoxyguanosine; LC/MS analysis of the adducts revealed the same major
      (protonated) adduct at m/z = 464.4 as previously reported for the DNA adduct
      formed (in vivo or in vitro) by the mixed function-catalyzed bioactivation
      system. None of the peroxidase-catalyzed IQ metabolites (nitro-, azo-, or azoxy
      IQ) were detected. In conclusion, hydrogen peroxide in the
      physiological/pathological concentration range may be able to support the
      metabolic activation of arylamines to genotoxic products through the cytochrome
      P450 peroxygenase pathway.

PMID- 9168258
TI  - Metabolism of the cytochrome P450 mechanism-based inhibitor N-benzyl-1
      aminobenzotriazole to products that covalently bind with protein in guinea pig
      liver and lung microsomes: comparative study with 1-aminobenzotriazole.
AB  - The metabolism and covalent binding of radioactivity to microsomal protein of the
      cytochrome P450 (P450) mechanism-based inhibitors 1-amino-[14C]-2,3-benzotriazole
      ([14C]ABT) and two radiolabeled forms of N-benzyl-1-aminobenzotriazole (BBT), N
      benzyl-1-amino-[14C]-2,3-benzotriazole ([14C]-2,3-BBT) and [14C]-N-7-benzyl-1
      aminobenzotriazole ([14C]-7-BBT), were examined in hepatic or pulmonary
      microsomes from untreated and phenobarbital (PB)- or beta-naphthoflavone (betaNF)
      induced guinea pigs. [14C]-2,3-BBT and [14C]-7-BBT were converted to multiple
      metabolites including ABT, benzotriazole, benzaldehyde, 2- or 3-hydroxy-BBT, and
      4-hydroxy-BBT by hepatic microsomes, while [14C]ABT, whose primary metabolite was
      benzotriazole, underwent little biotransformation. Neither ABT nor BBT was
      extensively metabolized by pulmonary microsomes. Hepatic microsomes from betaNF
      (vs PB)-treated guinea pigs metabolized [14C]ABT, [14C]-2,3-BBT, and [14C]-7-BBT
      more extensively. The degree of NADPH-dependent covalent binding of [14C]-2,3-BBT
      or [14C]-7-BBT-derived radioactivity (1.0 nmol/mg of protein) was higher than
      that of [14C]ABT (0.3-0.8 nmol/mg of protein) in hepatic microsomes, especially
      those from PB-induced animals. Covalent binding per nmol of P450 in pulmonary
      microsomes was 3-4-fold higher with [14C]-2,3-BBT (2.9 nmol/nmol of P450) than
      with [14C]-7-BBT (1.0 nmol/nmol of P450), whereas in hepatic microsomes from PB-
      or betaNF-treated animals the ratio of binding with the two forms of BBT was
      approximately 1:1. [14C]-2,3-BBT- and [14C]-7-BBT-derived radioactivity was
      covalently bound to proteins that migrated in the molecular weight region
      corresponding to P450 on SDS-PAGE following incubation with NADPH. These data
      indicate that BBT is metabolized to at least two reactive compounds capable of
      covalent modification of protein and/or a single reactive product is formed which
      contains both the benzo ring (of benzotriazole) and the benzyl carbon atom (of
      the N-benzyl group); that P450 apoprotein modification may be an important
      mechanism of inactivation of pulmonary and hepatic P450 by BBT; and that hepatic
      microsomes from betaNF-induced guinea pigs generate more metabolites that do not
      act as mechanism-based P450 inhibitors from BBT than do those from PB-induced
      animals.

PMID- 9168259
TI  - Mechanism-based inactivation of cytochrome P450 2B1 by N-benzyl-1
      aminobenzotriazole.
AB  - The kinetics of inactivation of cytochrome P450 2B1, the major phenobarbital
      inducible rat hepatic P450, by N-benzyl-1-aminobenzotriazole (BBT) were
      characterized. Purified, reconstituted P450 2B1 7-ethoxy-4
      (trifluoromethyl)coumarin (7-EFC) O-deethylase activity was inhibited by BBT in a
      mechanism-based manner. The loss of O-deethylase activity followed pseudo-first
      order kinetics and was NADPH and BBT dependent. After a 5 min incubation, greater
      than 90% of the 2B1 activity was lost, whereas more than 70% of the ability of
      the reduced enzyme to bind CO was maintained. Inclusion of 10 mM glutathione in
      the inactivation reaction lowered the rate of inactivation (k(inactivation)) and
      increased the partition ratio without significantly affecting the inactivator
      concentration required for half-maximal inactivation (K(I)). The maximal rate
      constant for inactivation at 23 degrees C was 0.24 min(-1) without and 0.15 min(
      1) with glutathione. The apparent K(I) was 2 microM in both cases. The
      extrapolated partition ratios were 4 and 9 without and with 10 mM glutathione,
      respectively. Consistent with mechanism-based inactivation, the loss of 7-EFC O
      deethylase activity was irreversible, was not due to product inhibition, was
      saturable, and could be slowed by including increasing concentrations of
      competing substrate. However, the inactivated P450 2B1 was still able to
      metabolize substrate if iodosobenzene was used as an alternate oxidant.
      Inactivation of 2B1 with either N-[14C]-7-benzyl-1-aminobenzotriazole (BBT) or N
      benzyl-1-amino-[14C]-2,3-benzotriazole resulted in the incorporation of covalent
      radiolabel into the apoprotein. The stoichiometry of labeled metabolite adduct to
      protein was approximately 0.4:1 in both cases. Identification of metabolites
      revealed the formation of 1-aminobenzotriazole, benzotriazole, benzaldehyde, and
      a new metabolite (27) during catalysis of BBT by P450 2B1. Together, these data
      suggest that P450 2B1 could be inactivated and labeled by more than one
      metabolite.

PMID- 9168260
TI  - Role of cytochrome P450 enzyme induction in the metabolic activation of
      benzo[c]phenanthrene in human cell lines and mouse epidermis.
AB  - The environmental contaminant benzo[c]phenanthrene (B[c]Ph) has weak carcinogenic
      activity in rodent bioassays; however, the fjord region diol epoxides of B[c]Ph,
      B[c]Ph-3,4-diol 1,2-epoxides (B[c]PhDE), are potent carcinogens. To determine the
      role of cytochrome P450 isozymes in the activation of B[c]Ph in MCF-7 cells and
      the low activation of B[c]Ph in mouse skin, cells of the MCF-7 and the human
      hepatoma HepG2 cell lines were treated with the potent Ah receptor agonist
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) prior to exposure to B[c]Ph for 24 h.
      Mice were treated topically with 1 microg of TCDD or vehicle (control) for 73 h
      and then with 2 micromol of B[c]Ph for 24 h. In MCF-7 cells, TCDD exposure
      increased B[c]PhDE-DNA adduct levels more than 3-fold with a 10-fold increase in
      the (-)-B[c]PhDE-2-dA(t) adduct. Treatment of HepG2 cells with TCDD prior to
      B[c]Ph application did not increase B[c]PhDE-DNA binding. Total B[c]PhDE-DNA
      adducts increased 3-fold in TCDD-treated mouse epidermis: the majority of the
      increase resulted from (+)-B[c]PhDE-1-dA adducts. Analysis of P450 enzymes by
      Western blotting detected a large increase of P4501B1 but almost no increase in
      P4501A1 in MCF-7 cells exposed to 10 microM B[c]Ph for 24 or 48 h. In HepG2
      cells, there were no detectable levels of P4501A1 or P4501B1 after treatment with
      10 microM B[c]Ph for 24 h. In contrast, topical application of 2 micromol of
      B[c]Ph to mouse skin for 48 or 72 h increased P4501A1, but no P4501B1 was
      detected. As a measure of P450 activity, the metabolism of 7,12
      dimethylbenz[a]anthracene (DMBA) was analyzed in microsomes prepared from MCF-7
      and HepG2 cells exposed to 0.1% DMSO, 10 microM B[c]Ph, or 10 nM TCDD for 24 or
      48 h and from mouse epidermis treated with 1 microg of TCDD, or vehicle control
      for 72 h, or 2 micromol of B[c]Ph for 48 h. The levels of DMBA metabolites were
      low or undetectable in microsomes from B[c]Ph-treated MCF-7 and HepG2 cells, but
      a metabolite pattern consistent with P4501A1 metabolism of DMBA was present in
      B[c]Ph-exposed mouse epidermal microsomes. TCDD-treated MCF-7 cells, HepG2 cells,
      and mouse epidermis had DMBA metabolism patterns characteristic of P4501A1
      activity. Microsomes from TCDD-treated human cells formed a higher proportion of
      the proximate carcinogenic metabolite DMBA-3,4-dihydrodiol (16% of total
      identified metabolites) than TCDD-treated mouse epidermis (2%). In mouse
      epidermis, the weak ability of B[c]Ph to increase hydrocarbon-metabolizing
      activity and the increase in mainly P4501A1, leading to formation of the less
      carcinogenic stereoisomer B[c]PhDE-1, may explain the low carcinogenic activity
      of B[c]Ph. In a human mammary carcinoma cell line, treatment with B[c]Ph
      increases mainly P4501B1 and results in formation of a higher proportion of the
      more carcinogenic B[c]PhDE-2. This indicates that cells in which B[c]Ph treatment
      increases P4501B1 levels effectively activate B[c]Ph to potent carcinogenic
      metabolites.

PMID- 9168261
TI  - Inactivation of the inducible nitric oxide synthase by peroxynitrite.
AB  - The simultaneous production of superoxide and nitric oxide by stimulated human
      neutrophils leads to the formation of peroxynitrite, a physiologically important
      bactericidal agent. We have investigated two possible pathways for the
      inactivation of inducible nitric oxide synthase (NOS-II) by peroxynitrite:
      inactivation of NOS-II through oxidation of the tightly bound cofactor calmodulin
      (CaM) and direct interaction of ONOO-/ONOOH with the NOS-II protein. Studies of
      two model peptides indicated that the Ca2+-dependent binding to CaM of a typical
      high-affinity sequence, melittin, significantly prevented Met oxidation in CaM by
      ONOO-/ONOOH. In contrast, binding of the putative CaM-binding domain of human
      hepatocyte NOS-II (NOS-II509-534) to CaM only marginally prevented the oxidation
      of Met residues in CaM. When the native NOS-II/CaM complex was exposed to
      peroxynitrite, CaM was inert toward oxidation. Nevertheless, even small amounts
      of peroxynitrite abolished the activity of NOS-II through direct interaction with
      the heme. The loss of activity was paralleled by a decrease in heme absorbance
      and a shift of the absorbance maximum from 419 to 409 nm. The presence of the
      cofactor tetrahydrobiopterin during peroxynitrite exposure did not prevent
      inactivation of the enzyme but altered the change of the heme spectrum, i.e., a
      shift of lambda(max) from 419 to 420 nm rather than to 409 nm. In conclusion,
      peroxynitrite inactivates NOS-II through changes in the heme or its environment
      in NOS-II rather than via oxidation of the cofactor CaM.

PMID- 9168262
TI  - I. Serotonin (5-HT) within dopamine reward circuits signals open-field behavior.
      II. Basis for 5-HT--DA interaction in cocaine dysfunctional behavior.
AB  - Light microscopic immunocytochemical studies, using a sensitive silver
      intensification procedure, show that dopamine (DA) and serotonin (5-HT) axons
      terminate on neurons in the nucleus accumbens (NAcc) (A10) terminals and also in
      dorsal striatum (DSTr) (A9) terminals. The data demonstrate a prominent
      endogenous anatomic interaction at these distal presynaptic sites between the
      neurotransmitters 5-HT and DA; the pattern of the 5-HT-DA interaction differs
      between A10 and A9 terminals. Moreover, in distinction to the variance shown
      anatomically between 5-HT--DA interactions at distal A9 and A10 sites, the 5-HT-
      DA interactions at the level of DA somatodendrites, the proximal site, are
      similar, i.e. 5-HT terminals in the midbrain tegmentum are profuse and have a
      massive overlap with DA neurons in both ventral tegmental area (VTA) and
      substantia nigra pars compacta (SNpc). We suggest with reference to the DA
      neurons of A10 and A9 pathways, inclusive of somatodendrites (sites of proximal
      presynaptic interactions in the midbrain) and axons (sites of distal presynaptic
      interactions), that 5-HT--DA interactions in A10 terminals are more likely to
      exceed those in the DStr arrangement. Furthermore, our neuroanatomic data show
      that axonally released DA at A10 terminals may originate from proximal 5-HT
      somatodendrites, i.e. dorsal raphe (DR) or the proximal DA somatodendrites, VTA.
      In vivo microvoltammetric studies were done with highly sensitive temporal and
      spatial resolution; the studies demonstrate basal (endogenous) real time 5-HT
      release at distal A10 and distal A9 terminal fields and real time 5-HT release at
      proximal A10 VTA somatodendrites. In vivo microvoltammetric studies were
      performed concurrently and on line with studies of DA release, also at distal A10
      and distal A9 terminal fields and at proximal A10 somatodendrites. Serotonin
      release was detected in a separate voltammetric peak from the DA voltammetric
      peak. The electrochemical signal for 5-HT release was detected within 10-12 s and
      that for DA release within 12-15 s, after each biogenic amine diffused through
      the synaptic environment onto the microelectrode surface. The electrochemical
      signal for 5-HT and a separate electrochemical signal for DA are detected on the
      same voltammogram within 22-27 s; each electrochemical signal represents current
      changes in picoamperes, within seconds of detection time. The amplitude of each
      electrochemical signal reflects the changes in diffusion of each biogenic amine
      to the microelectrode surface. Each neurotransmitter has a distinct potential at
      which oxidation occurs; this results in a recording which has a distinct peak for
      a specific neurotransmitter. The concentration of each neurotransmitter within
      the synaptic environment is directly related to the electrochemical signal
      detected via the Cottrell equation. Voltammograms were recorded every 5 min. At
      the time that basal 5-HT release and basal DA release were recorded within same
      animal control, open-field behavioral studies were performed, also concurrently,
      by infrared photocell beams. The frequency of each behavioral parameter was
      monitored every 100 ms; the number of behavioral events, were summated every 5
      min during the time course of study. Thus, the detection of neurotransmitters
      occurs in real time, while simultaneously monitoring the animal's behavior by
      infrared photocell beams. The results from the in vivo microvoltammetric and
      behavioral data from this study show that basal 5-HT release at distal A10 and A9
      terminals dramatically increased with DA release. Moreover, each increase in
      basal 5-HT release, at both A10 and at A9 terminal fields occurred consistently
      and at the same time as each increase in open-field locomotion and stereotypy
      occurred naturally during the animal's exploration in a novel chamber. Thus, the
      terminology 'synchronous and simultaneous' describes aptly the correlation
      between 5-HT release at distal A10 and A9 terminal fields and open-field locomo

PMID- 9168263
TI  - The behavior of the Japanese or domestic quail Coturnix japonica.
AB  - This paper reviews the literature pertaining to the behavior of the Japanese or
      domestic quail Coturnix japonica. Details are given of the classification,
      characteristics, domestication and the economic and research potential of the
      species. Further sections deal with sensation and perception (including taste and
      smell, vision and hearing), maintenance behavior (including feeding and drinking,
      dust bathing and thermoregulation), development and aging (including
      vocalization, filial imprinting, sexual imprinting, fear and avoidance responses,
      sexual maturation and aging), adult learning (including habituation, instrumental
      conditioning, Pavlovian conditioning and observational learning), photoperiodism,
      reproductive behavior (including courtship and mating, hormonal control and
      ontogeny of sexual differentiation, and male and female sexual behavior),
      parental behavior (including nest-site selection and nest building, incubation
      behavior and its hormonal control, and hen-chick relationships), and aggressive
      behavior and dominance (including agonistic behavior and the hormonal control of
      aggressive behavior).

PMID- 9168264
TI  - Outlining a brain model of mental imaging abilities.
AB  - This paper outlines a brain model of mental imaging abilities by reviewing
      neuropsychological evidence of the association and dissociation between mental
      imaging processes and known perceptual mechanisms; differentiating between visual
      mode and auditory-mode thought systems; pointing to brain arousal systems
      involved in waking and dream imaging; and exploring pre-frontal involvement in
      deliberate imaging and cognitive state monitoring. In the process, the paper
      develops an emerging distinction between objective-imagery and subjective-imagery
      abilities. It ends by suggesting possible brain models for in-born and clinical
      loss of subjective imaging abilities.

PMID- 9168265
TI  - 3-Nitropropionic acid animal model and Huntington's disease.
AB  - Huntington's disease (HD) is a progressive neurodegenerative disorder associated
      with severe degeneration of basal ganglia neurons, especially the intrinsic
      neurons of the striatum, and characterized by progressive dementia and
      involuntary abnormal choreiform movements. Despite our increasing knowledge of
      the pathophysiology of HD, culminating with the discovery of the gene underlying
      HD, there has been no cure available to completely cease or reverse the
      progressive neurodegeneration and behavioral consequences of the disease. Animal
      models that closely mimic the neurobiological and clinical symptoms of the
      disease continue to offer alternative approaches for studying HD. Recently, we
      have reported that systemic administration of 3-nitropropionic acid (3-NP), an
      inhibitor of the mitochondrial citric acid cycle, results in a progressive
      locomotor deterioration resembling that of HD. Furthermore, we observed congruent
      with other reports, that 3-NP produces a very selective striatal degeneration. It
      differs mechanistically from excitotoxic lesions in that 3-NP irreversibly
      inhibits the mitochondrial citric acid cycle and leads to depressed ATP levels
      and elevated lactate concentrations. Recent neurochemical studies have implicated
      lowered glutamate levels and impaired oxidative energy metabolism as underlying
      mechanisms for many neurodegenerative disorders, including HD. Because of the
      mechanistic and pathologic similarities between 3-NP lesions and HD, 3-NP has
      been proposed as an alternative HD model. We further demonstrated that
      manipulating the time course of 3-NP injections leads to sustained hyperactivity
      (early HD) or hypoactivity (late HD). The present review will primarily discuss
      this progressive behavioral pathology induced by 3-NP that closely resembles that
      of HD. This body of evidence suggests that the 3-NP model is an improved HD model
      and may offer a unique system wherein testing of experimental treatments for HD
      can be carried out across different stages of the disease. This future
      application of the 3-NP model will be very useful especially in assessing the
      efficacy of treatment modalities, e.g. neural transplantation, during the
      progression of the disease.

PMID- 9168266
TI  - Relative effects of carbohydrates and protein on satiety -- a review of
      methodology.
AB  - There is some evidence that the effects of carbohydrates and protein may differ
      with respect to satiety. This may depend in part on the different methods of
      preparing these nutrients for administration. Additional factors such as timing,
      different delays, differential metabolism and expectations of ingested foods may
      contribute to different outcomes of experiments investigating the satiating
      effects of macronutrients. Here, studies of the relative satiating effects of
      carbohydrates and protein are discussed followed by a methodological discussion
      of the reviewed studies. Finally, suggestions for methodological improvements are
      given which should allow future studies to investigate more clearly the
      mechanisms underlying satiety.

PMID- 9168267
TI  - The neurobiology of social play behavior in rats.
AB  - Social play behavior is one of the earliest forms of non-mother-directed social
      behavior appearing in ontogeny in mammalian species. During the last century,
      there has been a lot of debate on the significance of social play behavior, but
      behavioral studies have indicated that social play behavior is a separate and
      relevant category of behavior. The present review provides a comprehensive survey
      of studies on the neurobiology of social play behavior. Evidence is presented
      that opioid and dopamine systems play a role in the reward aspect of social play
      behavior. The role of cholinergic, noradrenergic and opioid systems in
      attentional processes underlying the generation of social play behavior and the
      involvement of androgens in the sexual differentiation of social play behavior in
      rats is summarized. It is concluded that there is not only behavioral, but also
      neurobiological evidence to suggest that social play behavior represents a
      separate category of behavior, instead of a precursor for adult social, sexual or
      aggressive behavior.

PMID- 9168268
TI  - Neurobehavioral alterations in autoimmune mice.
AB  - Inbred MRL, NZB and BXSB strains of mice spontaneously develop a systemic, lupus
      like autoimmune disease. The progress of autoimmunity is accompanied with a
      cascade of behavioral changes, most consistently observed in tasks reflective of
      emotional reactivity and the two-way avoidance learning task. Given the
      possibility that behavioral alterations may reflect a detrimental consequence of
      autoimmune-inflammatory processes and/or an adaptive response to chronic malaise,
      they are tentatively labeled as autoimmunity-associated behavioral syndrome
      (AABS). It is hypothesized that neuroactive immune factors (pro-inflammatory
      cytokines, brain-reactive antibodies) together with endocrine mediators
      (corticotropin-releasing factor, glucocorticoids) participate in the etiology of
      AABS. Since AABS develops natively, and has a considerable face and predictive
      validity, and since the principal pathway to autoimmunity is known, AABS may be a
      useful model for the study of CNS involvement in human autoimmune diseases and by
      extension, for testing autoimmune hypotheses of several mental disorders (major
      depression, schizophrenia, Alzheimer's disease, autism and AIDS-related
      dementia).

PMID- 9168269
TI  - Behavioral functions of nucleus accumbens dopamine: empirical and conceptual
      problems with the anhedonia hypothesis.
AB  - Nucleus accumbens (DA) has been implicated in a number of different behavioral
      functions, but most commonly it is said to be involved in "reward" or
      "reinforcement". In the present article, the putative reinforcement functions of
      accumbens DA are summarized in a manner described as the "General Anhedonia
      Model". According to this model, the DA innervation of the nucleus accumbens is
      conceived of as a crucial link in the "reward system", which evolved to mediate
      the reinforcing effects of natural stimuli such as food. The reward system is
      said to be activated by natural reinforcing stimuli, and this activation mediates
      the reinforcing effects of these natural stimuli. According to this view, other
      stimuli such as brain stimulation and drugs can activate this system, which leads
      to these stimuli being reinforcing as well. Interference with DA systems is said
      to blunt the reinforcing effects of these rewarding stimuli, leading to
      "extinction". This general model of the behavioral functions of accumbens DA is
      utilized widely as a theoretical framework for integrating research findings.
      Nevertheless, there are several difficulties with the General Anhedonia Model.
      Several studies have observed substantial differences between the effects of
      extinction and the effects of DA antagonism or accumbens DA depletions. Studies
      involving aversive conditions indicate that DA antagonists and accumbens DA
      depletions can interfere with avoidance behavior, and also have demonstrated that
      accumbens DA release is increased by stressful or aversive stimuli. Although
      accumbens DA is important for drug abuse phenomena, particularly stimulant self
      administration, studies that involve other reinforcers are more problematic. A
      large body of evidence indicates that low doses of dopamine antagonists, or
      depletions of accumbens DA, do not impair fundamental aspects of food motivation
      such as chow consumption and simple instrumental responses for food. This is
      particularly important, in view of the fact that many behavioral researchers
      consider the regulation of food motivation to be a fundamental aspect of food
      reinforcement. Finally, studies employing cost/benefit analyses are reviewed, and
      in these studies considerable evidence indicates that accumbens DA is involved in
      the allocation of responses in relation to various reinforcers. Nucleus accumbens
      DA participates in the function of enabling organisms to overcome response costs,
      or obstacles, in order to obtain access to stimuli such as food. In summary,
      nucleus accumbens DA is not seen as directly mediating food reinforcement, but
      instead is seen as a higher order sensorimotor integrator that is involved in
      modulating response output in relation to motivational factors and response
      constraints. Interfering with accumbens DA appears to partially dissociate the
      process of primary reinforcement from processes regulating instrumental response
      initiation, maintenance and selection.

PMID- 9168270
TI  - Didelphid behavior.
AB  - There are approximately 75 species of American opossums (didelphids). Systematic
      behavioral research has been reported for only a small number of species, namely,
      Monodelphis domestica and Didelphis virginiana. Observational studies and field
      reports on several other didelphid species have also been published. The current
      review covers behavioral studies on didelphids including research on
      territoriality, reproductive behaviors, parturition, maternal behaviors, nest
      building, vocalizations, scent-marking, circadian rhythms, swimming, locomotion,
      discrimination learning, maze learning, operant learning, problem box learning,
      exploration, death-feigning, predatory behavior, and prey manipulation. Didelphid
      behavior is compared in several contexts with eutherian mammals. Other than death
      feigning, which has only been reported for one or two didelphid species, the
      behaviors observed in didelphids are qualitatively similar to those of eutherian
      mammals. Nevertheless, differences can be seen in prey manipulation and spatial
      maze behavior. Social interactions appear to be sparser in opossums than in most
      eutherian mammals. However, the scarcity of systematic research on didelphid
      behavior still prevents firm conclusions regarding these ancient and interesting
      mammals. Futher research on didelphids is warranted, particularly since they
      provide a natural comparison group for small generalist eutherians.

PMID- 9168271
TI  - The delayed-conditional-discrimination task improves measurement of working
      memory in rats.
AB  - The validity of delayed-matching-to-sample (DMTS) and related tasks executed in
      skinner boxes as an animal model for human working memory (WM) is confounded by
      the occurrence of mediating behaviour during delays. True matching, a
      supplementary task during delays and response similarity are ways to deal with
      this problem. However, until now rats have not been able to learn a true matching
      task in Skinner boxes and introduction of a supplementary task during delays does
      not sufficiently prevent mediating behaviour. Response similarity, on the other
      hand, effectively prevents the use of mediating behaviour by reducing the
      discriminative value of the behaviour during delays. Furthermore, it is argued
      that the interpretation of drug effects is confounded by baseline performance and
      mediating behaviour. It is shown that high baseline levels and high amounts of
      mediating behaviour can induce delay dependent drug effects, suggesting a
      specific effect on WM. We therefore assert that examination of delay-dependency
      of a drug effect alone is not sufficient to claim specific effects of a drug on
      WM. The delayed-conditional-discrimination (DCD) task uses response similarity to
      effectively reduce mediating behavior and does not generate high levels of
      baseline performance. The DCD task is therefore preferred over other tasks for
      the measurement of WM in rats using Skinner boxes.

PMID- 9168272
TI  - Medicine and public health join forces.

PMID- 9168273
TI  - Prostate cancer's complexities of causation, detection, and treatment challenge
      researchers.

PMID- 9168274
TI  - President limits secret experiments on humans.

PMID- 9168275
TI  - From the Centers for Disease Control and Prevention. Surveillance for penicillin
      nonsusceptible Streptococcus pneumoniae--New York City, 1995.

PMID- 9168276
TI  - From the Centers for Disease Control and Prevention. Tobacco tax initiative-
      Oregon, 1996.

PMID- 9168277
TI  - From the Centers for Disease Control and Prevention. Urban community intervention
      to prevent halloween arson--Detroit, Michigan, 1985-1996.

PMID- 9168278
TI  - A piece of my mind. For everything a blessing.

PMID- 9168279
TI  - Usefulness of oral mucosal transudate for HIV antibody testing.

PMID- 9168280
TI  - Usefulness of oral mucosal transudate for HIV antibody testing.

PMID- 9168281
TI  - Usefulness of oral mucosal transudate for HIV antibody testing.

PMID- 9168282
TI  - Usefulness of oral mucosal transudate for HIV antibody testing.

PMID- 9168283
TI  - Prognostic implications of elevated creatine kinase after coronary angioplasty.

PMID- 9168284
TI  - Prognostic implications of elevated creatine kinase after coronary angioplasty.

PMID- 9168285
TI  - The rational clinical examination: detecting abnormal systolic murmurs.

PMID- 9168286
TI  - The rational clinical examination: detecting abnormal systolic murmurs.

PMID- 9168287
TI  - More on dietary sodium and blood pressure.

PMID- 9168288
TI  - A national strategy for research in chronic obstructive pulmonary disease.

PMID- 9168289
TI  - Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for
      48 hours in the treatment of acute spinal cord injury. Results of the Third
      National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute
      Spinal Cord Injury Study.
AB  - OBJECTIVE: To compare the efficacy of methylprednisolone administered for 24
      hours with methyprednisolone administered for 48 hours or tirilazad mesylate
      administered for 48 hours in patients with acute spinal cord injury. DESIGN:
      Double-blind, randomized clinical trial. SETTING: Sixteen acute spinal cord
      injury centers in North America. PATIENTS: A total of 499 patients with acute
      spinal cord injury diagnosed in National Acute Spinal Cord Injury Study (NASCIS)
      centers within 8 hours of injury. INTERVENTION: All patients received an
      intravenous bolus of methylprednisolone (30 mg/kg) before randomization. Patients
      in the 24-hour regimen group (n=166) received a methylprednisolone infusion of
      5.4 mg/kg per hour for 24 hours, those in the 48-hour regimen group (n=167)
      received a methylprednisolone infusion of 5.4 mg/kg per hour for 48 hours, and
      those in the tirilazad group (n=166) received a 2.5 mg/kg bolus infusion of
      tirilazad mesylate every 6 hours for 48 hours. MAIN OUTCOME MEASURES: Motor
      function change between initial presentation and at 6 weeks and 6 months after
      injury, and change in Functional Independence Measure (FIM) assessed at 6 weeks
      and 6 months. RESULTS: Compared with patients treated with methylprednisolone for
      24 hours, those treated with methylprednisolone for 48 hours showed improved
      motor recovery at 6 weeks (P=.09) and 6 months (P=.07) after injury. The effect
      of the 48-hour methylprednisolone regimen was significant at 6 weeks (P=.04) and
      6 months (P=.01) among patients whose therapy was initiated 3 to 8 hours after
      injury. Patients who received the 48-hour regimen and who started treatment at 3
      to 8 hours were more likely to improve 1 full neurologic grade (P=.03) at 6
      months, to show more improvement in 6-month FIM (P=.08), and to have more severe
      sepsis and severe pneumonia than patients in the 24-hour methylprednisolone group
      and the tirilazad group, but other complications and mortality (P=.97) were
      similar. Patients treated with tirilazad for 48 hours showed motor recovery rates
      equivalent to patients who received methylprednisolone for 24 hours. CONCLUSIONS:
      Patients with acute spinal cord injury who receive methylprednisolone within 3
      hours of injury should be maintained on the treatment regimen for 24 hours. When
      methylprednisolone is initiated 3 to 8 hours after injury, patients should be
      maintained on steroid therapy for 48 hours.

PMID- 9168290
TI  - Effectiveness of a violence prevention curriculum among children in elementary
      school. A randomized controlled trial.
AB  - OBJECTIVE: To determine if a commonly used violence prevention curriculum, Second
      Step: A Violence Prevention Curriculum, leads to a reduction in aggressive
      behavior and an increase in prosocial behavior among elementary school students.
      DESIGN: Randomized controlled trial. SETTING: Urban and suburban elementary
      schools in the state of Washington. PARTICIPANTS: Six matched pairs of schools
      with 790 second-grade and third-grade students. The students were 53% male and
      79% white. INTERVENTION: The curriculum uses 30 specific lessons to teach social
      skills related to anger management, impulse control, and empathy. MAIN OUTCOME
      MEASURES: Aggressive and prosocial behavior changes were measured 2 weeks and 6
      months after participation in the curriculum by parent and teacher reports
      (Achenbach Child Behavior Checklist and Teacher Report Form, the School Social
      Behavior Scale, and the Parent-Child Rating Scale) and by observation of a random
      subsample of 588 students in the classroom and playground/cafeteria settings.
      RESULTS: After adjusting for sex, age, socioeconomic status, race, academic
      performance, household size, and class size, change scores did not differ
      significantly between the intervention and control schools for any of the parent
      reported or teacher-reported behavior scales. However, the behavior observations
      did reveal an overall decrease 2 weeks after the curriculum in physical
      aggression (P=.03) and an increase in neutral/prosocial behavior (P=.04) in the
      intervention group compared with the control group. Most effects persisted 6
      months later. CONCLUSIONS: The Second Step violence prevention curriculum appears
      to lead to a moderate observed decrease in physically aggressive behavior and an
      increase in neutral and prosocial behavior in school.

PMID- 9168291
TI  - Characteristics of women with and without breast augmentation.
AB  - OBJECTIVE: To compare selected characteristics of women with and without
      augmentation mammaplasty to identify differences between these 2 groups of women.
      DESIGN AND STUDY PARTICIPANTS: White women identified as controls in previously
      conducted population-based, case-control studies formed the study population for
      the present cross-sectional analysis (N=3570). MAIN OUTCOME MEASURE: Interview
      information on selected characteristics was compared between women who had
      received augmentation mammaplasty (n=80) and other women (n=3490) using the
      prevalence odds ratio (pOR) as the measure of association. RESULTS: Women with
      breast implants were more likely to drink a greater average number of alcoholic
      drinks per week (for > or =7 drinks vs 0 drinks: pOR=2.9, 95% confidence interval
      [CI]=1.5-5.5), be younger at first pregnancy (for age <20 years vs age 20-29
      years: pOR=1.6, 95% CI=1.0-2.7), be younger at first birth (for age <20 years vs
      age 20-29 years: pOR=1.9, 95% C1=1.1-3.3), have a history of terminated
      pregnancies (for > or =1 termination vs 0 terminations: pOR=2.0, 95% CI=1.2-3.4),
      have ever used oral contraceptives (pOR=2.2, 95% CI=1.0-4.7), have ever used hair
      dyes (pOR=4.5, 95% CI=1.3-15.4), and have had a greater lifetime number of sexual
      partners (for > or =14 partners vs < or =4 partners: pOR=8.9, 95% CI=3.1-25.5)
      than other women. A history of smoking, lactation, high blood pressure, or
      thyroid disorders, as well as the number of pregnancies, full-term births, or
      miscarriages, differed little between women with and without implants. Women with
      breast augmentation were much less likely to be heavy than other women (for > or
      =74 kg vs <56 kg: pOR=0.1, 95% CI=0.03-0.3). CONCLUSION: The differences we found
      between women with and without breast implants suggest that consideration and
      evaluation of confounding factors in future studies will help to clarify some of
      the long-term health consequences of having breast implants.

PMID- 9168292
TI  - Depressive symptoms and the cost of health services in HMO patients aged 65 years
      and older. A 4-year prospective study.
AB  - OBJECTIVE: To examine whether depressive symptoms in older adults contribute to
      increased cost of general medical services. DESIGN: A 4-year prospective cohort
      study. SETTING: Four primary care clinics of a large staff-model health
      maintenance organization (HMO) in Seattle, Wash. PATIENTS: A total of 5012
      Medicare enrollees older than 65 years were invited to participate in the study;
      2558 subjects (51%) were successfully enrolled. Non-participants were somewhat
      older and had a higher level of chronic medical illness. MAIN OUTCOME MEASURES:
      Depressive symptoms as measured by the Center for Epidemiological Studies
      Depression scale, which was administered as part of a mail survey at baseline, at
      2 years, and at 4 years; and total cost of medical services from the perspective
      of the HMO. Data were obtained from the cost accounting system of the HMO.
      RESULTS: In this cohort of older adults, depressive symptoms were common,
      persistent, and associated with a significant increase in the cost of general
      medical services. This increase was seen for every component of health care costs
      and was not accounted for by an increase in specialty mental health care. The
      increase in health care costs remained significant after adjusting for
      differences in age, sex, and chronic medical illness. CONCLUSIONS: Depressive
      symptoms in older adults are associated with a significant increase in the cost
      of medical services, even after adjusting for the severity of chronic medical
      illness.

PMID- 9168293
TI  - Effects of oral potassium on blood pressure. Meta-analysis of randomized
      controlled clinical trials.
AB  - OBJECTIVE: To assess the effects of supplementation with oral potassium on blood
      pressure in humans. DESIGN: Meta-analysis of randomized controlled trials. DATA
      SOURCES: English-language articles published before July 1995. STUDY SELECTION:
      Thirty-three randomized controlled trials (2609 participants) in which potassium
      supplementation was the only difference between the intervention and control
      conditions. DATA EXTRACTION: Using a standardized protocol, 2 of us independently
      abstracted information on sample size, duration, study design, potassium dose,
      participant characteristics, and treatment results. RESULTS: By means of a random
      effects model, findings from individual trials were pooled, after results for
      each trial were weighted by the inverse of its variance. An extreme effect of
      potassium in lowering blood pressure was noted in 1 trial. After exclusion of
      this trial, potassium supplementation was associated with a significant reduction
      in mean (95% confidence interval) systolic and diastolic blood pressure of -3.11
      mm Hg (-1.91 to -4.31 mm Hg) and -1.97 mm Hg (-0.52 to -3.42 mm Hg),
      respectively. Effects of treatment appeared to be enhanced in studies in which
      participants were concurrently exposed to a high intake of sodium. CONCLUSIONS:
      Our results support the premise that low potassium intake may play an important
      role in the genesis of high blood pressure. Increased potassium intake should be
      considered as a recommendation for prevention and treatment of hypertension,
      especially in those who are unable to reduce their intake of sodium.

PMID- 9168294
TI  - An 88-year-old woman facing the end of life.

PMID- 9168295
TI  - A 64-year-old man with adult-onset diabetes, 1 year later.

PMID- 9168296
TI  - Applying science to violence prevention.

PMID- 9168297
TI  - More breast implant prose and cons. Contractures and confounding: the controversy
      continues.

PMID- 9168298
TI  - Arizona overwhelmingly adopts health care initiative.

PMID- 9168299
TI  - Chronic myelomonocytic leukemia: from biology to therapy.
AB  - Chronic myelomonocytic leukemia represents a distinct myelodysplastic syndrome in
      which an excess of monocytes is observed both in the blood and bone marrow of the
      patients. Whereas diagnosis is relatively easy, therapeutic design and efficacy
      is difficult and no treatment has to date provided complete or significant
      partial response. In vitro data suggest that the growth and differentiation of
      myelomonocytic progenitors may be altered inasmuch as monocytic or granulo
      macrophagic colonies show spontaneous growth. Different entities may be observed:
      the childhood form, Juvenile Chronic Myelomonocytic Leukemia (JCML) shows in
      vitro a typical pattern with constitutive growth of only macrophagic colonies and
      hypersensitivity to GM-CSF; in the adult form at least two patterns may be
      observed one close to the JCML form and one more heterogeneous with absence of GM
      CSF sensitivity and spontaneous growth of both CFU-GM and CFU-M colonies.
      Chemotherapy reduces all myeloid colonies in vitro whereas retinoic acid has a
      selective effect on monocytic colonies with a concomitant increase of CFU-G
      colonies forwarding an explanation for the correction of pancytopenia observed in
      some patients. Recent analysis of altered molecular pathways in this disease
      suggest a common disruption of intracellular signalling pathways namely the Ras
      pathway and targetting for drugs with may selectively control or inhibit a
      constitutive activation may forward novel therapeutic perspectives.

PMID- 9168300
TI  - The ex vivo expansion capacity of normal human bone marrow cells is dependent on
      experimental conditions: role of the cell concentration, serum and CD34+ cell
      selection in stroma-free cultures.
AB  - The present study was conducted to establish defined culture conditions for ex
      vivo expansion of normal human bone marrow cells. We investigated the role of
      three experimental expansion parameters: the cell concentration in the initial
      culture medium, the role of animal serum, human plasma and serum-free substitute,
      and the expansion potential of mononucleated cells (MNC) versus CD34+ cells.
      Cells were cultured in suspension with stem cell factor (SCF), IL3, IL6 and
      Erythropoietin (Epo) for 10 days. 1) Reducing the cell concentration from 3 x
      10(4) to 1.5 x 10(3)/ml increased total cell expansion almost 20 fold, progenitor
      expansion more than 3 fold, and the maintenance of long term culture-initiating
      cells (LTC-IC). 2) In medium containing a serum-free substitute, total and CD34+
      cell expansion was 3 times greater than in medium containing 1-10% human AB
      plasma or 25% animal serum. 3) The expansion potential of selected CD34+ cells
      was significantly greater than that of the total MNC population. However, taking
      into account the cell loss due to CD34+ selection, the overall results for
      quantitative expansion in relation to the initial number of MNCS favor the use of
      non-selected MNCS. 4) SCF + IL3 + IL6 was clearly the best combination of early
      cytokines for LTC-IC maintenance, with or without lineage-restricted cytokines,
      whereas the presence of IL1 beta in any combination augmented the decrease in LTC
      IC. Addition of G-CSF to the medium resulted in 1 log increase in total cell
      expansion and a 2-fold increase in CFU-GM expansion. Addition of Epo always
      induced a dramatic proliferation of erythroid cells (up to 2000 fold) as well as
      of CFU-GM (up to 4 fold), without exhausting the LTC-IC pool. We concluded that
      the expansion of hemopoietic cells for clinical purposes needs establishment of
      controlled, reproducible and reliable culture conditions.

PMID- 9168302
TI  - Comparison of T cell depletion strategies from bone marrow, umbilical cord and
      peripheral blood using five separation systems.
AB  - The development of bone marrow transplantation in mismatched or matched unrelated
      donor situations, the recent use of peripheral blood stem cells for allogeneic
      transplants, the standardization and respect of good methodology practices
      highlight the need to evaluate new safe methods of T cell depletion (TCD). We
      have performed 79 in vitro TCD using five techniques: rabbit complement
      cytotoxicity, CD2-CD7 immunomagnetic depletion, CD5-CD8 panning system, CD34
      positive purging and counterflow centrifugation elutriation (CCE). We analyzed
      these different approaches with regard to the degree of T and B depletion,
      recovery of progenitors and NK cells. In our hands, the 5 systems evaluated
      showed a TCD of between 1.3 and 3 log. The CCE, immunomagnetic, complement and
      panning methods all give similar a TCD of around 2 log. In contrast, we obtained
      a TCD of approximately 3 log with CD34 positive purging. The progenitor yield was
      around 50% regardless of the technique used. However, the degree of B and NK cell
      depletion was dependent on the method: specific TCD resulted in low BCD (under
      0.5 log), whereas CCE or CD34 positive purging gave a BCD of greater than 1 log.
      Moreover, CD34 positive selection resulted in a virtually complete elimination of
      NK cells. CCE was the only technique allowing isolation of the small lymphocyte
      population which can be useful for adoptive therapy. To obtain TCD over three
      logarithms, double purging techniques are necessary. Because specific roles of T
      cells subsets in engraftment, graft versus host disease, Epstein Barr virus
      associated B cell lymphoproliferative disorders and disease relapse have not yet
      been completely elucidated, new techniques such as CD34 positive purging and
      double purging methods (positive and negative purging) need to be clinically
      evaluated, especially with respect to peripheral blood stem cells.

PMID- 9168301
TI  - Results of three courses of adriamycin, bleomycin, vindesine, and dacarbazine
      with subtotal nodal irradiation in 189 patients with nodal Hodgkin's disease
      (stage I, II and IIIA).
AB  - AIM OF THE STUDY: To evaluate in a prospective trial three courses of an ABVD
      like chemotherapy (CT) regimen given before radiation therapy (RT) (subtotal
      nodal irradiation (STNI) in favorable stage Hodgkin's disease (HD). The efficacy,
      risk factors and medium-term toxicities are reported. PATIENT CHARACTERISTICS:
      Stage I or II with at least one of the following factors, mediastinal
      involvement, histological type 3, age > 40 years, ESR rate > 50 mm, or stage
      IIIA. 189 patients with newly diagnosed HD were treated between 01/89 and 01/94
      (stage I, n = 33; stage II, n = 129, stage IIIA, n = 27). Three courses of an
      ABVD-like regimen (adriamycin 25 mg/m2, bleomycin 10 mg, vindesine 2 mg/m2 and
      dacarbazine 250 mg/m2 day 1 and 8) were given before STNI at 36/40 grays. At
      diagnosis, prognostic factors were distributed as follows: B symptoms (n = 54),
      bulky mediastinum (n = 41), hemoglobin < 12 g/dl (n = 37), ESR > 50 (n = 65), age
      > 45 (n = 24). RESULTS: After chemotherapy, 90% had an objective response
      (partial response > 75%) and 98% were in complete remission (CR) at the end of
      RT. Three patients had primary refractory disease and 13 patients (7%) relapsed,
      3 at the initial site, 4 at previously uninvolved sites and 6 at both. With a
      median follow-up of 60 months, 170 patients are in 1st CR, 5 in 2nd or greater CR
      and 11/14 patients have died from HD. Bulky mediastinum (p = 0.009), age > 45
      years (p = 0.03) and EST > 50 mm (p = 0.05) were adverse prognostic factors for
      survival. Bulky mediastinum (p = 0.009) was the only prognostic factor for
      freedom from progression. TOXICITIES: Two patients died from treatment related
      toxicity and one patient died with an osteogenic sarcoma. No secondary leukemia
      has so far been detected. 24 pregnancies were reported. Cardiopulmonary toxicity
      was always < grade 1 (WHO) in 95 patients evaluated. Two patients over 45 years
      old had a myocardial infarction. CONCLUSION: With an acceptable medium-term
      toxicity, this treatment achieved 85% survival at 5 years.

PMID- 9168303
TI  - Expression of CD95(FAS) by gene transfer does not sensitize K562 to Fas-killing.
AB  - CD95(FAS/Apo-1) belongs to the family of TNF receptor related molecules and is
      expressed on many benign and malignant types of cells. CD95 triggering is
      involved in the apoptotic death of lymphoid cells and may also be important in
      myelopoiesis. Myeloid leukemia cells are in most cases resistant to CD95
      triggering despite expressing the antigen. We reasoned that myeloid leukemic
      cells can become sensitized to the Fas pathway of cell death if CD95 expression
      is restored by gene transfer. As a model, we utilized the cell line K562 which
      does not express CD95 on their cell surface. The gene for CD95 was introduced
      into K562 cells (by electroporation). As a control, the gene coding for beta
      galactosidase was used. The CD95 transfected K562 cells stably expressed CD95,
      and had a growth pattern comparable to untransfected cells, but still remained
      resistant to Fas-triggering (tested using recombinant Fas-ligand). Our experiment
      shows that antigen expression is not a critical determinant of Fas-mediated
      apoptosis, but further down-stream mechanisms determine the fate of the cells.
      The transfected cells also had a comparable susceptibility to NK-mediated lysis
      which shows that the expression of CD95 does not interfere with NK-mediated lysis
      of target cells.

PMID- 9168304
TI  - High-dose chemotherapy and autologous hematopoietic stem cell transplantation in
      patients with second primary malignancies.
AB  - We treated 500 patients with high-dose chemotherapy and autologous bone marrow or
      autologous peripheral blood stem cell transplantation. Treated conditions
      included leukemia, lymphoma, breast cancer, lung cancer, germ-cell carcinoma, and
      other solid tumors. 10/500 (2%) of patients were treated for a second malignancy
      diagnosed 12 months to 25 years after their initial neoplasm. Four of these ten
      patients are in complete remission (CR) of both malignancies at a median follow
      up of 29+ months after high-dose chemotherapy and autotransplantation. None of
      these patients would have been eligible for high-dose chemotherapy and
      autotransplantation by conventional selection criteria which usually excluded
      patients with a history of prior malignancies. Conclusion. Conventional exclusion
      criteria for high-dose chemotherapy and autotransplantation may not adequately
      reflect the prognosis of patients with second or secondary malignancies treated
      with this therapeutic modality. High-dose chemotherapy and autologous
      hematopoietic stem cell transplantation may be of true benefit in selected cases
      of secondary malignancies.

PMID- 9168305
TI  - Parvovirus B19 associated neutropenia. Treatment with Rh G-CSF.
AB  - In a 39-year-old patient under follow-up for metastatic adenocarcinoma of the
      colon, a post-operative fever and a profound neutropenia occurred during
      hospitalization. A diagnosis of primary infection with parvovirus B-19 was made
      in view of the association of reticulocytopenia, together with anti-B19 IgM
      antibodies and positive serum results for viral DNA. The granulocytic lineage
      appeared to be normal on bone-marrow smears, and anti PMN autoantibodies were not
      found. Rh G-CSF therapy resulted in a sharp increase in the PMN count. Although
      the pathophysiology of B19-associated neutropenia remains unclear, Rh G-CSF seems
      to be effective in this disorder.

PMID- 9168306
TI  - Listeriosis after fludarabine treatment for chronic lymphocytic leukemia.
AB  - The authors report a case of Listeria monocytogenes septicemia in a patient with
      advanced CLL after a single course of fludarabine, without any other
      immunosuppressive therapy e.g. corticosteroids. The immunosuppressive action of
      fludarabine in patients who are already severely immunosuppressed must be
      considered from a diagnostic and therapeutic point of view. Listeriosis and other
      opportunistic infections, like pneumocystis carinii pneumonia, have been reported
      during and after treatment with purine analogues. Prophylaxis with cotrimoxazole
      must therefore be discussed in patients with CLL treated with fludarabine.

PMID- 9168307
TI  - Suppression or overexpression of genes encoding myeloid growth factors or their
      receptors.
AB  - Gene inactivation data have documented that erythropoietin, G-CSF, M-CSF and
      thrombopoietin are major regulators in vivo respectively of red cell, neutrophil,
      macrophage and platelet production. Transgenic mice can provide valuable models
      for observing the consequences of excessive stimulation by a particular growth
      factor but are subject to variation based on the use of differing promoters for
      the inserted gene.

PMID- 9168308
TI  - Pathophysiology of Kostmann syndrome: the G-CSF receptor issue.
AB  - Kostmann Syndrome is defined as a chronic neutropenia, dating from early
      childhood, characterized typically by a granulopoeisis impairment at the
      promyelocyte stage. The origin is not yet understood. G-CSF receptor anomaly -the
      intra-cellular carboxy terminal region- was noted in a few patients (6 out of
      54), initially in two patients who later developed secondary leukemia. More
      follow-up, with other patients, led us to consider the mutation of the G-CSF
      receptor sometimes as a transient event, not systematically resulting in
      malignancy. This finding directs research toward intra-cellular signaling pathway
      in a pathology that raises questions both of granulopoeisis and leukemogenesis.

PMID- 9168309
TI  - The use of cytokines in the treatment of solid tumours.
AB  - This manuscript reviews the clinical trials with cytokines in solid tumors.
      Starting with Interleukin 2 alone or in association with other cytokines and
      chemotherapy, the reviews opens the prospects of future direction for the use of
      cytokines as adjuvant therapy, for vaccination or to inhibit the growth activity
      of certain cytokines.

PMID- 9168310
TI  - C-kit mutations and mast cell disorders. A model of activating mutations of
      growth factor receptors.
AB  - Mastocytosis are a group of diseases characterized by abnormal proliferation of
      mast cells. Various forms are observed in respect to the organ system involving,
      clinical manifestations, and association with hematological disorders. The c-kit
      proto-oncogene encodes for a receptor tyrosine kinase, which plays a crucial role
      in hematopoiesis, especially in mast cell growth and differentiation. Mutations
      in the tyrosine kinase domain of c-kit have been reported in murine and human
      malignant cell lines, and more recently in some cases of human mast cell
      diseases. The biochemical and clinical aspects of these mutations are reviewed
      with special emphasis on the experiments which demonstrate their role in
      oncogenesis and mast cell proliferation.

PMID- 9168311
TI  - Lactic acid bacteria of foods and their current taxonomy.
AB  - Application of molecular genetic techniques to determine the relatedness of food
      associated lactic acid bacteria has resulted in significant changes in their
      taxonomic classification. During the 1980s the genus Streptococcus was separated
      into the three genera Enterococcus, Lactococcus and Streptococcus. The lactic
      acid bacteria associated with foods now include species of the genera
      Carnobacterium, Enterococcus, Lactobacillus, Lactococcus, Leuconostoc,
      Oenococcus, Pediococcus, Streptococcus, Tetragenococcus, Vagococcus and
      Weissella. The genus Lactobacillus remains heterogeneous with over 60 species
      (ymol% G+C content ranging from 33 to 55), of which about one-third are strictly
      heterofermentative. However, many changes have been made and reorganization of
      the genus along lines that do not follow previous morphological or phenotypic
      differentiation from Leuconostoc and Pediococcus is being studied.
      Phylogenetically belonging to the Actinomyces branch of the bacteria,
      Lactobacillus bifidus has been moved to the genus Bifidobacterium also on account
      of its greater than 50 mol% G+C content. It is therefore no longer considered one
      of the lactic acid bacteria senso strictu, which form part of the Clostridium
      branch of the bacteria. The new genus Weissella has been established to include
      one member of the genus Leuconostoc (Leuc, paramesenteroides) and
      heterofermentative lactobacilli with unusual interpeptide bridges in the
      peptidoglycan. Contrary to the clear-cut division of the streptococci,
      morphological and physiological features of Weissella do not directly support
      this grouping which now incorporates species that produce D(-)- as well as DL
      lactate. The new genus Carnobacterium is morphologically similar to the
      lactobacilli, but it shares some physiological similarities (e.g. growth at pH
      9.5) and a common phylogenetic branch with the genus Enterococcus. The review
      includes information on the taxonomic changes and the relationship of the
      bacteria of food fermentation and spoilage.

PMID- 9168312
TI  - Determination of ready-to-eat vegetable salad shelf-life.
AB  - The shelf-life of ready-to-eat vegetable salads established by manufacturers is
      usually 7-14 days depending on the type of vegetable, and is determined by loss
      in organoleptic qualities. A more objective method to predict shelf-life and
      spoilage would be desirable. The present study monitored the evolution of
      spoilage organisms in a mixed salad of red cabbage, lettuce and carrot stored at
      4 degrees C, 10 degrees C and 15 degrees C. Changes in carbon dioxide and oxygen
      concentrations and pH were also monitored. Predictive modelling was used to
      established a theoretical shelf-life time as a function of temperature. Lactic
      acid bacteria at levels of 10(6) cfu/g appeared to be related to both spoilage
      and theoretically-predicted shelf-life values.

PMID- 9168313
TI  - Comparison of a protein phosphatase inhibition assay, HPLC assay and enzyme
      linked immunosorbent assay with the mouse bioassay for the detection of
      diarrhetic shellfish poisoning toxins in European shellfish.
AB  - Consumption of shellfish contaminated with algal toxins produced by marine
      dinoflagellates can lead to diarrhetic shellfish poisoning (DSP). UK legislation
      necessitates toxin detection by mouse bioassay but this method is non-specific
      and lacks sensitivity. As an alternative method, an HPLC technique has been
      optimized, with detection limits of 0.26 micrograms of toxin/g of shellfish
      hepatopancreas for both Okadaic Acid (OA) and Dinophysistoxin-1 (DTX-1). A
      colorimetric protein phosphatase inhibition (PPI) assay has also been optimized.
      This assay detects inhibition of protein phosphatase 1 (PPI gamma) by OA and DTX
      1 with detection limits of 1.5 ng of total toxin/g of hepatopancreas.
      Contaminated shellfish from several European sources, the UK monitoring
      programmes and mussels associated with an outbreak of DSP poisoning in the UK,
      have been analyzed and assessed using the two alternative methods and a
      commercially available enzyme-linked immunosorbent assay (ELISA) kit. The results
      indicate that both the HPLC and PPI assays correlate well with each other and
      with the UK standard mouse bioassay. In contrast, and not withstanding its
      advantages of rapidity and ease, the ELISA kit did not accurately and
      consistently detect low toxin concentrations, although it may be useful as a
      screening tool.

PMID- 9168314
TI  - Time-to-turbidity model for non-protective type B Clostridium botulinum.
AB  - A model to predict the time for growth to turbidity from spores of non
      proteolytic type B strains of Clostridium botulinum was developed in broth media
      with varying temperatures (4-28 degrees C), pH values (5-7), NaCl additions (0
      4%) and total spores (10(1)-10(5)). The model estimates the probability that a
      sample will have growth on a given day for up to 90 days of storage. The
      parameters of the model include the probability of growth after 90 days (Pmax)
      and the mean time of growth (tau) for those that showed growth. The 95%
      confidence interval (CI95%) for tau was also determined. The tau decreased with
      increasing temperature and pH, but NaCl levels below 3% had little effect.
      Decreasing the number of spores in a sample increased both tau and the confidence
      intervals about tau, reflecting the increasing uncertainty about the estimation
      of growth times for low spore numbers.

PMID- 9168315
TI  - Microbial quality of lamb carcasses during processing and the acridine orange
      direct count technique (a modified DEFT) for rapid enumeration of total viable
      counts.
AB  - This study was designed to set up a hazard analysis and critical control points
      (HACCP) system for sheep slaughtering operations at four different plants in
      Ireland and to determine the differences between plants in terms of microbial
      contamination. A single carcass area, the abdomen, was examined by swabbing and a
      microbiological profile was determined at different stages along the slaughter
      line. The level of contamination was assessed from the total bacteria counts,
      Enterobacteriaceae and Listeria spp. For the total counts, a modified direct
      epifluorescent filter technique (acridine orange direct count technique (AODC))
      was developed and tested. No significant differences were found among plants in
      the levels of bacterial contamination. This was observed for all groups of
      organisms. The rapid direct technique (AODC) was found to be very successful. A
      correlation coefficient of 0.87 was obtained for this method and the standard
      plate count. Each test could be carried out in about 10-15 min and could be used
      to predict the standard plate count.

PMID- 9168316
TI  - Control of Yersinia enterocolitica in raw pork and pork products by gamma
      irradiation.
AB  - gamma-Radiation response of Y. enterocolitica 5692 and 152 was studied at 0
      degrees C and at -40 degrees C in phosphate buffer (pH 7.00) as well as in 10%
      raw meat/salami homogenate. The strains investigated did not differ in their
      response and were found to be sensitive to gamma-radiation but exhibited a
      tailing phenomenon in the survival curve. The D10 in homogenate was 0.25 kGy at 0
      degrees C. This response was not affected at -40 degrees C. Storage studies of
      packs, inoculated artificially with heavy inoculum of Y. enterocolitica (10(6)
      cfu/g) showed that while samples of salami and cooked ham could be decontaminated
      at doses of 4 and 3 kGy respectively; cells could not be eliminated from raw pork
      meat even at the higher dose of 6 kGy. The role of different treatments given
      prior to irradiation for revival of Y. enterocolitica after irradiation storage
      was studied. The dose of 1 kGy at -40 degrees C was efficient in eradicating low
      numbers (< 10(3)) of naturally occurring of Y. enterocolitica from raw pork meat
      without any revival during storage at refrigeration temperature.

PMID- 9168317
TI  - Amino acid requirements for the growth and enterotoxin production by
      Staphylococcus aureus in chemically defined media.
AB  - The production of enterotoxins A, B, and C by five strains of Staphylococcus
      aureus was studied in a series of defined media, each differing from the complete
      defined medium in the lack of one amino acid. Valine was required for growth;
      arginine and cystine for growth and enterotoxin production. Omission of
      individual amino acid affected in different ways the yields of the toxins
      produced.

PMID- 9168318
TI  - Dental identification of war victims from Petrinja in Croatia.
AB  - In this paper the authors report their experiences and problems encountered in
      the identification of war victims from Petrinja in Croatia. Soon after Croatian
      forces regained Petrinja in 1995, four mass graves were discovered from which the
      bodies of 46 civilians, 38 males and 8 females, were recovered. Identification of
      the victims was performed at the Department of Forensic Medicine and Criminology
      at the School of Medicine in Zagreb. A forensic odonto-stomatologist from the
      Department of Dental Anthropology of the School of Dental Medicine at the
      University of Zagreb participated in the identification process by carrying out
      dental identifications. A total of 27 victims (59%) were identified, while 19
      (41%) are at present still unidentified. Identification by supportive and
      anthropological evidence (e.g. sex, age, height, personal documents, dress,
      jewellery) was achieved in 43% of cases, while identification based only on
      dental records was achieved in 16%. The most useful dental characteristics for
      the purpose of identification were fixed and removable prosthetic appliances for
      oral rehabilitation. The reason for the low number of dental identifications was
      the lack of antemortem dental data which could be compared with postmortem dental
      records.

PMID- 9168319
TI  - Radial alveolar count as a tool for the estimation of fetal age.
AB  - A total of 53 normal fetuses with a gestational age ranging from 15 up to 39
      weeks was investigated and the radial alveolar count (RAC) was estimated as a
      parameter for lung maturation. Values lower than 2.0 could only be found in lungs
      of fetuses aged less than 18 weeks. Between 18 and 25 weeks of gestation,
      relatively constant levels of RAC were observed but with considerable
      interindividual variation. In fetuses with a gestational age of more than 25 and
      especially 30 weeks, a slight or rapid increase in RAC occurred respectively.
      Values lower than 3.0 were found up to a fetal age of less than 30 weeks and a
      RAC of more than 4.0 was only found in lungs of fetuses aged more than 30 weeks.
      Values exceeding 6.0 occurred only in fetuses at near full-term birth. Since the
      estimation of RAC overcomes the effects of varying degrees of alveolar collapse,
      such an analysis also seems to be useful for the determination for fetal age in
      cases of advanced putrefaction.

PMID- 9168320
TI  - A comparison of 3H-cocaine binding on melanin granules and human hair in vitro.
AB  - The in vitro experiments on the interaction of 3H-cocaine and melanin from Sepia
      officinalis confirmed the existence of drug binding sites on melanin granules.
      The results suggested that the binding of 3H-cocaine to melanin could be analyzed
      by assuming that the binding to the surface of pigment granules is analogous to
      the adsorption of a drug on a solid and follows Langmuir adsorption isotherm type
      I. Scatchard analysis indicated heterogeneity of binding sites. Structural and
      chemical alterations caused by isolation of the melanoproteins, which are
      heterogeneous in nature and show different physico-chemical properties, are
      considered to be most crucial. The studies on hair samples confirmed that melanin
      drug interaction occur on the surface of melanin granules. These seem to be of
      minor importance compared to the drug-melanoprotein loading during melanogenesis
      for the observed influence of pigmentation on the drug content of hair fibers.
      From the results it was concluded that in vitro studies on melanin provide
      limited information and even drug-soaked hair must be regarded as inappropriate
      for the study of melanin-drug-binding in hair.

PMID- 9168321
TI  - Reaction patterns in selected lymphatic tissues associated with sudden infant
      death (SID).
AB  - In 50 cases of sudden infant death cervical, paratracheal and lung hilar lymph
      nodes, the thymus and the spleen were investigated by histology and
      immunohistochemistry (CD 20, 21, 45RO). The cases were divided into 3 groups
      based on autopsy findings including extensive histology: A --without pathological
      changes (N = 12), B --with minimal to intermediate inflammation (N = 23) and C -
      with severe inflammation (N = 15). In accordance with previous results the
      frequency of "pathological" lymph node changes, such as paracortical lymphoid
      hyperplasia and variegated hyperplasia of the pulp increased from group A to
      group C. The B-cell antigens reacted accordingly. A pronounced lymphodepletation
      of the thymus as a sign of a long lasting stimulation of the T-cell system was
      also observed increasingly from group A to C. In summary, in none of the cases
      results obtained were indicative of a defect of the T- or B-cell system. The
      results in group A seem to indicate that changes in the reaction pattern of the
      lymphoid tissues could be a more sensitive method of detection of early stages of
      inflammation than local histology.

PMID- 9168322
TI  - Sequence polymorphism at the tetranucleotide repeat of the human beta-actin
      related pseudogene H-beta-Ac-psi-2 (ACTBP2) locus.
AB  - The tetranucleotide repeat polymorphism in the human beta-actin related
      pseudogene H-beta-Ac-psi-2 (ACTBP2) locus has become a widely used short tandem
      repeat (STR) system in paternity testing and human identification. The
      discrimination index of this locus has been reported to be as high as 99.65%. To
      study the overall variability of this locus, 222 alleles were sequenced in our
      laboratory. Here, we report the sequences of the 102 different alleles observed.
      In addition to the length polymorphism, up to ten different sequence variants for
      single fragment lengths have been detected.

PMID- 9168323
TI  - Forensic diaphanoscopy: how to investigate invisible subcutaneous hematomas on
      living subjects.
AB  - A significant proportion of subcutaneous hematomas remain undetected after
      external visual examination of the body. In the case of a cadaver such hematomas
      can be easily identified through a cutaneous incision but in living persons the
      diagnosis becomes more complicated. The usual methods, based on diagnostic
      imaging, do not combine sufficient reliability and feasibility. The results of
      our investigations demonstrated that forensic diaphanoscopy is a highly sensitive
      (95%) and specific (97%) means to determine the presence or absence of
      subcutaneous invisible hematomas. In addition, it is possible to locate such
      hematomas with great precision, to draw their shape and evaluate their magnitude.
      The lower limit of detection is of the order of 1 mm. The advantages of this
      method lie in the fact that it is reliable, non-invasive, has no side effects, is
      simple to carry out and allows real time scanning.

PMID- 9168324
TI  - Prior exposure of the entrance wound region from clothing is uncommon in firearm
      suicides.
AB  - According to an old rule still in use, gunshot suicides will rarely shoot through
      the clothing but will pull it aside to bare the skin. Thus, a bullet defect in
      the clothing would be an indicator for homicide or an accident. A total of 138
      clearly defined gunshot suicides were analysed with regard to this topic. The
      thorax, which is commonly covered by textile, was the target for 27 suicides
      (19.5%). Of these 27 persons, 25 had fired through the clothing and 2 had placed
      the muzzle directly on the exposed skin, which represents a relative frequency of
      only 7%. Special features such as thick clothing or an affected state of mind did
      not appear to influence this behavior. Consequently, the perforation of textile
      does not suggest homicide or an accident - it is not applicable as a criterion
      for distinguishing different modes of death. Only in the rare cases when a
      gunshot victim is found with intact clothing covering the entrance wound can this
      finding be interpreted as an indication for suicide.

PMID- 9168325
TI  - The destabilizing effect of body armour on military rifle bullets.
AB  - Soft body armour is designed to give protection against fragments and some low
      velocity bullets but is not designed to stop high velocity rifle bullets. Reports
      have claimed that soft body armour might disturb the stability of bullets that
      penetrate it, and that this might increase the size of the lesions. The reason
      for such an effect might be early yaw of the bullet, so we studied the behaviour
      of bullets which had passed through soft body armour. A 7.62 x 39 mm AK-47 rifle
      was fired from a permanent stand using full metal jacketed lead core bullets at a
      range of 30 m. Soft body armour composed for 14 and 28 layers of aramid fibres
      (Kevlar) was placed at 90 degrees and 60 degrees to the line of fire. Yaw was
      measured by the shadowgraph technique and a TERMA Doppler radar. A total of ten
      shots without body armour, and ten shots with each of the two types of body
      armour at the two angles were used. The results of the shadowgraph and Doppler
      radar measurements showed a proportional correlation between the two methods of
      determining the bullet yaw. The semiquantitative approach of the Doppler radar
      measurement was in agreement with the more concise measurement using the
      photographic technique. Velocity loss and loss of spin rate from penetrating 14
      or 28 ply Kevlar was negligible. We observed induced instability after
      penetration of 14 and particularly 28 ply Kevlar, dependence of yaw with respect
      to the number of layers of Kevlar as well as to the angle of the body armour with
      respect to the line of fire.

PMID- 9168326
TI  - Self-implanted subcutaneous penile balls--a new phenomenon in Western Europe.
AB  - The subcutaneous self-implantation of spherical objects in the penis is a well
      known practice among members of the Yakuza in Japan but this phenomenon has not
      previously been described in the Western world. However, recently there were two
      cases in Berlin of young Eastern Europe men in whom implanted penile balls as in
      the Yakuza were found at autopsy. Investigations in Russia revealed that this
      phenomenon is typically encountered there among prisoners and in certain army
      units. In addition to the feeling of belonging to a specific group, increased
      sexual confidence is one major reason for these implantations that are usually
      performed under primitive conditions.

PMID- 9168327
TI  - Laceration of the thoracic aorta from a .22 lr bullet.
AB  - A gunshot wound (.22 long rifle) to the chest including perforation of the aorta
      ascendens is presented. The small wound tract in soft tissue was characteristic
      for this type of ammunition and did not show any special peculiarities. However,
      arterial injury was not restricted to two small perforations, as expected in the
      light of previous wound ballistic findings. Three large longitudinal ruptures
      (3.0-4.5 cm in length and two of them independent of the perforations)
      additionally occurred, which led to rapid exsanguination. This extraordinary
      extent of vascular injury can be explained by perforation of the artery during
      the ventricular ejection phase, which causes a considerable dilation of the aorta
      analogous to a windkessel. The pre-existing dilation enables intraluminal
      temporary cavitation to have an "explosive" effect despite the high elastic
      tolerance to the vessel wall. The importance of tissue characteristics in gunshot
      wounds in general and the possible role of temporary cavitation inside the vessel
      in vascular gunshot wound production in particular are stressed.

PMID- 9168328
TI  - Acute fatal poisoning with dichlorophen.
AB  - A case is presented involving an acute fatality resulting from self-administered
      dichlorophen, a chlorophenol fungicide. The compound was quantified using gas
      chromatography/mass spectrometry after extraction with methyl-tert-butyl ether,
      derivatization by methylation and separation on a HP5-MS capillary column. The
      blood concentration was 9.77 mg/l and other drugs, including ethanol, were not
      detected.

PMID- 9168329
TI  - The diagnosis of a murder from skeletal remains: a case report.
AB  - A skeletonised body was found in a Danish forest. The examination of the bones
      revealed several incision on the skeleton, one located on the cervical column,
      two on the sternum, one perforating incision to the right iliac crest, and
      several superficial ones to the ribs and the right tibia. The skeletonized body
      was thought to be that of a young man in the twenties with a height of 170 cm. It
      was estimated that the body has been lying at the spot for at least 1 or 2 y and
      had been murdered by several stab wounds to the chest and abdomen. Police
      enquiries subsequently revealed that the deceased was a 23-year-old male with a
      height of 171 cm. A man confessed to having murdered the victim 1 1/2 years
      earlier with several stab wounds to the face/neck, chest, abdominal wall and
      thigh.

PMID- 9168330
TI  - STR analysis on perforating FMJ bullets and a new VWA variant allele.
AB  - In three separate shooting incidents involving multiple gunshots, two FMJ bullets
      and one bullet fragment found at the scene (one from each case) were investigated
      for the presence of biological material from the victim after perforation. The
      surface of the missiles, which did not show obvious tissue traces when examined
      under a macroscope, was swabbed. PCR typing of up to five STR loci was performed
      on the small amounts of DNA extracted, which were seen below the detection limit
      of the slot blot quantification in one case. Nevertheless, individualisation of
      cellular material from the perforating projectiles was successful in each of the
      three cases presented. Consequently, identification of the victim wounded by a
      perforating bullet can reliably be achieved if contamination or removal of
      evidentiary material by improper handling is prevented. This technique is
      especially useful in cases where more than one person has fired a gun because the
      bullet carrying DNA can be linked to the firearm by investigation with a
      comparison microscope. As a by-product of this investigation, a variant allele 14
      (14+4) at the VWA locus was detected.

PMID- 9168332
TI  - A population study of the STR loci HUMLPL, HUMF13B, and HUMF13A01 in Hungary.
AB  - Allele frequencies of the three STR systems HUMLPL, HUMF13B, and HUMF13A01 were
      determined in a Hungarian population sample of 223 unrelated Caucasian
      individuals. All loci met Hardy-Weinberg expectations and there was no evidence
      for association of alleles among the three STR loci. In addition, little evidence
      was found for departures from expectations of independence between any of the
      three STR and other previously investigated microsatellite polymorphisms.

PMID- 9168331
TI  - Sudden unexpected death due to Fournier's gangrene.
AB  - A 43-year-old Japanese male vagrant collapsed suddenly in a police station. The
      man was resuscitated in hospital but died about 13 h later. An autopsy revealed
      necrotizing fasciitis in the genitalia and lower abdominal wall. The man was
      considered to have died from endotoxic shock following on Fournier's gangrene.

PMID- 9168333
TI  - F13B and CD4 allele frequencies in south west Switzerland.
AB  - Allele frequencies of the two short tandem repeat (STR) systems F13B and CD4 were
      determined in a population sample from South West Switzerland using PCR analysis.
      We found five alleles for both STRs in a population sample of 205 unrelated
      individuals. No significant deviation from Hardy-Weinberg equilibrium was
      observed.

PMID- 9168334
TI  - North Italian population genetic data on the STR system HumFGA.
AB  - Frequency data for the STR system HumFGA were obtained from a North Italian
      population sample (Milano area) of 201 unrelated individuals. PCR products were
      detected by horizontal polyacrylamide gel electrophoresis and a total of 15
      alleles were identified by side-by-side comparison with a commercially available
      sequenced allelic ladder. The observed genotype distribution showed no
      significant deviation from Hardy-Weinberg equilibrium. The high information
      content (discrimination power > 0.96, polymorphism information content > 0.84)
      render this system a useful tool in forensic routine casework both in criminal
      and paternity cases.

PMID- 9168335
TI  - DYS19 marker in Japanese populations.
AB  - Allele frequencies of the Y chromosome-specific short tandem repeat system DYS19
      (Y-27H39) were determined from blood samples obtained from 251 unrelated Japanese
      in Fukui and Gunma Prefectures. Five alleles that contained 10, 11, 12, 13 and 14
      repeats of GATA were detected. Allele frequency distributions in Japanese
      populations were different from those in other Asian and Caucasian populations.

PMID- 9168336
TI  - Postmortem distribution pattern of morphine and morphine glucuronides in heroin
      overdose Skopp G et al.: Int J Legal Med (1996) 109:118-124.

PMID- 9168337
TI  - Implicit and explicit memory in obsessive-compulsive disorder.
AB  - We examined implicit and explicit memory in obsessive-compulsive disorder (OCD)
      patients an in non-patients. Implicit memory was measured by the effect of prior
      presentation on ratings of noise volume. Explicit memory was examined via a
      recognition task. We also investigated participants' confidence in the accuracy
      of their recognition. OCD patients rated noise accompanying contamination and
      neutral sentences as louder than did non-patients. Both groups rated noise
      accompanying contamination sentences as louder than noise accompanying neutral
      sentences. Also, both groups were less confident in their recognition of new
      contamination sentences compared to new neutral sentences, but this difference
      was less pronounced in the OCD group. The findings are discussed in light of
      previous research on memory in anxiety disordered individuals.

PMID- 9168338
TI  - Space and motion discomfort in Brazilian versus American patients with anxiety
      disorders.
AB  - Space and motion discomfort (SMD) was studied in 38 Brazilian and 50 U.S.
      patients belonging to one of three diagnostic groups: (a) panic disorder with
      agoraphobia, (b) panic disorder without agoraphobia, and (3) other nonpanic
      anxiety disorders. A group of 30 U.S. normal controls was also included. SMD was
      assessed by the Situational Characteristics Questionnaire (SitQ), which includes
      two scales for SMD--the Smd1 and the Smd2, and one scale for non-space-related
      agoraphobic discomfort, the Ag1. The score in the Smd2 is based on the sum of
      Likert style items, while the scores of the Smd1 and Ag1 are based on differences
      between contrasting subitems. A significant diagnosis effect was observed in all
      scales, with the highest scores in the agoraphobia group. A country effect was
      found only in the Smd2. A country effect was also observed when all subitems of
      the Smd1 and Ag1 were added rather than subtracted, suggesting that this country
      bias is related to a tendency of Brazilian patients to endorse symptoms.
      Implications of these findings to the trans-cultural validation of rating scales
      are discussed.

PMID- 9168339
TI  - Interpretive bias for benign sensations in panic disorder with agoraphobia.
AB  - The present study further examines the cognitive model of panic disorder by
      investigating two questions. The first is whether panic patients misinterpret
      bodily sensations which are symptoms of either nonanxious states or harmless
      events. The second is whether panic patients are able to provide benign
      subsequent explanations for bodily sensations which have initially been
      interpreted in an anxiety-related manner. Two groups of subjects were used, 15
      panic disorder patients with agoraphobia and 15 controls, matched on verbal
      fluency, age and gender. Compared to controls, patients failed to identify overt
      explanations for bodily sensations which are due to nonanxious states or harmless
      events. Patients also misinterpreted bodily sensations in ambiguous scenarios by
      providing more anxiety-related initial interpretations than controls.
      Furthermore, compared to controls, patients provided significantly more anxiety
      related initial interpretations which they were unable to subsequently
      reinterpret in a benign manner. These results provide support for the cognitive
      theory of panic disorder as authored by Clark and his colleagues.

PMID- 9168340
TI  - Cultural factors in social anxiety: a comparison of social phobia symptoms and
      Taijin kyofusho.
AB  - The present study examined two forms of culturally-defined social anxiety: social
      anxiety or phobia, as defined by DSM-IV; (i.e., a concern of public scrutiny or
      embarrassment) and Taijin Kyofusho (TKS), a Japanese form of social anxiety
      centered around concern for offending others with inappropriate behavior or
      offensive appearance. These versions of social anxiety are also examined in
      relation to culturally-determined self definition as independent and
      interdependent. One hundred eighty-one U.S. students and 161 students enrolled in
      Japanese universities were administered scales to assess social anxiety and
      phobia and TKS symptoms and behaviors, as well as construal of self as
      independent or interdependent. Factor analyses of the three scales used to assess
      social anxiety yielded three factors, each clearly corresponding to the
      respective scales and defining TKS and DSM-defined social anxiety. A case
      analysis indicated that there was an approximate 50% co-occurrence between high
      scorers on the TKS and social phobia scales. Multiple regression analyses
      resulted in a different set of predictors of TKS and SPS for the U.S. and
      Japanese respondents. Results were interpreted as suggesting that cultural
      variables can mediate the expression of social anxiety but that both forms of
      social anxiety can be found in each sample.

PMID- 9168341
TI  - Gender differences in dimensions of anxiety sensitivity.
AB  - Anxiety sensitivity (AS) is the fear of anxiety-related sensations arising from
      beliefs that these sensations have harmful physical, psychological, or social
      consequences. AS is measured using the Anxiety Sensitivity Index (ASI), a 16-item
      self-report questionnaire. Little is known about the origins of AS, although
      social learning experiences (including sex-role socialization experiences) may be
      important. The present study examined whether there were gender differences in:
      (a) the lower- or higher-order factor structure of the ASI; and/or (b) pattern of
      ASI factor scores. The ASI was completed by 818 university students (290 males;
      528 females). Separate principal components analyses on the ASI items of the
      total sample, males, and females revealed nearly identical lower-order three
      factor structures for all groups, with factors pertaining to fears about the
      anticipated (a) physical, (b) psychological, and (c) social consequences of
      anxiety. Separate principal components analyses on the lower-order factor scores
      of the three samples revealed similar unidimensional higher-order solutions for
      all groups. Gender x AS dimension analyses on ASI lower-order factor scores
      showed that: females scored higher than males only on the physical concerns
      factor; females scored higher on the physical concerns factor relative to their
      scores on the social and psychological concerns factors; and males scored higher
      on the social and psychological concerns factors relative to their scores on the
      physical concerns factor. Finally, females scored higher than males on the higher
      order factor representing the global AS construct. The present study provides
      further support for the empirical distinction of the three lower-order dimensions
      of AS, and additional evidence for the theoretical hierarchical structure of the
      ASI. Results also suggest that males and females differ on these various AS
      dimensions in ways consistent with sex role socialization practices.

PMID- 9168342
TI  - Trait anxiety: it's not what you think it is.
AB  - Trait anxiety began as a psychodynamic concept, poorly tied to observables, and
      requiring Freudian defense mechanisms to explain recurrent anxiety episodes.
      Spielberger's thoughtful efforts improved the concept, but some important
      limitations remained. Lilienfeld, Turner, and Jacob (1989, 1993, 1996)
      uncritically accepted Spielberger's work on trait anxiety and asserted that it is
      the standard against which the concept of anxiety sensitivity should be judged
      (see also Lilienfeld, 1996). Taylor (1996) and McNally (1989, 1996) distinguished
      anxiety sensitivity from trait anxiety by noting that, whereas trait anxiety
      predicts future anxiety generally, anxiety sensitivity predicts future fear to
      anxiety sensations specifically. An important additional difference is that the
      two constructs use different indicators (past anxiety experiences versus ASI
      beliefs) to predict future anxiety and fear. Furthermore, only anxiety
      sensitivity implies that some phobics perceive the feared object to be harmless;
      what they fear is an uncontrollable anxiety/panic reaction to the stimulus, not
      the dangerous nature of the stimulus itself.

PMID- 9168343
TI  - Normative data for the personal report of confidence as a speaker.
AB  - Normative data for the Personal Report of Confidence as a Speaker (PRCS; Paul,
      1966), a measure of public-speaking anxiety, were collected by administering the
      PRCS to 1109 college students. PRCS scores were examined in relation to gender,
      race, age, and grade-point average. No significant between-group differences were
      found. The findings indicate that levels of public-speaking anxiety are generally
      constant across gender, race, and age. Normative data for all scores across
      Caucasian and African-American subjects are presented.

PMID- 9168344
TI  - Current concepts: the stabilizing structures of the glenohumeral joint.
AB  - Significant contemporary advances have permitted a more comprehensive
      understanding and development of some interesting concepts about the glenohumeral
      joint. The purpose of this review paper was to discuss current concepts related
      to the anatomic stabilizing structures of the shoulder joint complex and their
      clinical relevance to shoulder instability. The clinical syndrome of shoulder
      instability represents a wide spectrum of symptoms and signs which may produce
      various levels of dysfunction, from subtle subluxations to gross joint
      instability. The glenohumeral joint attains functional stability through a
      delicate and intricate interaction between the passive and active stabilizing
      structures. The passive constraints include the bony geometry, glenoid labrum,
      and the glenohumeral joint capsuloligamentous structures. Conversely, the active
      constraints, also referred to as the active mechanisms, include the shoulder
      complex musculature, the proprioceptive system, and the musculoligamentous
      relationship. The interaction of the active and passive mechanisms which provide
      passive and active glenohumeral joint stability will be thoroughly discussed in
      this paper.

PMID- 9168345
TI  - The physical examination of the glenohumeral joint: emphasis on the stabilizing
      structures.
AB  - Thorough descriptions of specific physical examination tests used to determine
      glenohumeral instability are lacking in the scientific literature. The purpose of
      this paper was to discuss the importance of the subjective history and illustrate
      the physical examination of the glenohumeral joint. Additionally, the authors
      will illustrate specific stability assessment for the glenohumeral joint based on
      current basic science and clinical research. The physical examination of a
      patient whose history suggests subtle glenohumeral joint instability may be
      extremely difficult for the clinician due to the normal amount of capsular laxity
      commonly present in most individuals. An essential component of the physical
      examination is a through and meticulous subjective history which includes the
      mechanisms of injury and/or dysfunction, chief complaint, level of disability,
      and aggravating movements. The physical examination must include an assessment of
      motion, static stability testing, muscle testing, and a neurologic assessment. A
      comprehensive understanding of various stability testing maneuvers is important
      for the clinician to appreciate. The evaluation techniques discussed in this
      paper should assist the clinician in determining the passive stability of the
      glenohumeral joint.

PMID- 9168346
TI  - A taping technique for the treatment of acromioclavicular joint sprains: a case
      study.
AB  - Conservative treatment of Grade III acromioclavicular joint injuries usually
      consists of immobilization of the arm in a sling for 2-4 weeks followed by
      physical therapy. The initial phase of rehabilitation is greatly hindered by the
      fact that initial sling removal often exacerbates a patient's symptoms. This
      increase in pain leads to muscle guarding and spasms which, in turn, limit the
      extent of range of motion and strengthening exercises that can be performed. The
      purpose of this article is to describe a taping technique aimed at reducing a
      patient's pain in order to facilitate more rapid gains in range of motion,
      strength, and function. Two case studies are presented to better describe the
      indications for its use and demonstrate its intended results. The initial
      outcomes are promising for increasing patient's tolerance to physical therapy and
      thus, decreasing their length of stay.

PMID- 9168347
TI  - Isokinetic torque, average power, and flexion/extension ratios in nondisabled
      adults and adults with mental retardation.
AB  - For successful placement of individuals with mental retardation into community
      environments, a minimal amount of functional strength is required to promote self
      independence. Since muscular strength and power are commonly deficient in these
      groups, the purpose of this study was to compare isokinetic elbow flexion and
      extension peak torque (Nm), average power (W), and corresponding
      flexion/extension ratios of adults males with Down syndrome, with mental
      retardation without Down syndrome, and sedentary adult males without mental
      retardation. Subjects with Down syndrome (N = 9), mental retardation without Down
      syndrome (N = 13), and without mental retardation (N = 13) were tested for elbow
      flexion and extension peak torque and average power at 60 and 90 degrees/sec on a
      Cybex 340 isokinetic dynamometer. Results indicated: 1) subjects without mental
      retardation displayed significantly greater ( p < 0.01) peak torque and average
      power elbow flexion and extension than subjects with Down syndrome and subjects
      with mental retardation without Down syndrome at speeds of 60 and 90 degrees/sec,
      and 2) there were no significant differences between groups in peak torque and
      average power elbow flexion/extension ratios at both angular velocities. The
      results of the data analysis support the premise that adults with mental
      retardation are in need of exercise programs to improve muscular strength.

PMID- 9168348
TI  - Attitudes of physical therapists who possess sports specialist certification.
AB  - Physical therapists contemplating sports specialist certification need research
      based information to facilitate their decision-making process. The purpose of
      this study was to investigate the attitudes of physical therapists who have
      received sports specialist certification. These attitudes encompass the physical
      therapists' sense of fulfillment and their feelings of satisfaction or
      dissatisfaction with the certification process. Factors contributing to the
      therapist's decision to become sports specialist certified have also been
      investigated. Physical therapists who are sports certified specialists (N = 110)
      participated in this study. Questionnaires were mailed to the entire population
      of physical therapists who are sports certified specialists (N = 148). Frequency
      distributions and percentages were used on qualitative data, and mode was
      calculated for quantitative data. One hundred ten surveys were returned, for a
      response rate of 74.3%. Analysis of responses from the subject group suggests
      that physical therapists feel a high level of satisfaction with their decision to
      specialize, and that continued professional growth, development, and personal
      achievement are the major contributing factors in their decision to specialize.
      Based on these findings, physical therapists appeared to display overall
      satisfaction in their attitudes toward sports specialist certification. Further
      research may be warranted to further examine sports certified therapists'
      attitudes toward the specialization process.

PMID- 9168349
TI  - The growing use of echocardiography--a double-edged sword?
AB  - I believe that the growing volume of echocardiographic services is indeed a
      double-edge sword. On the one hand, it provides eloquent testimony to the
      versatility and perceived value of echocardiography to patient care. On the other
      hand, it underlines the significant resources consumed by providing these
      services. In these times of "do more with less," doing more can have some
      negative consequences. I believe that we must each act in a responsible manner,
      doing our part to be sure that the services we provide are truly needed. We must
      ask ourselves, and discuss with our referring physicians, "How will the results
      of this study alter patient care?" On occasion, we may find that a requested
      study really does not need to be performed. At the very least, this dialogue
      should allow us to refine the focus of the study and provide the most useful
      information to the treating physician. We must collect good outcomes data
      documenting those circumstances in which echocardiography improves outcomes and
      those clinical settings in which echocardiography is not helpful. We must
      continue to improve our skills to provide the best services to our patients. And
      we must also continue to adapt to changes in the health care environment. At the
      same time, I do not think that we can or should sacrifice quality in an effort to
      control costs. Clearly, incorrect or misleading information cannot be either cost
      effective or good for patient care. We must therefore continue to uphold high
      professional standards and to work with regulatory agencies ensure that the
      resources allocated to echocardiographic services are adequate to do them well.
      ASE's mission statement, which emphasizes that we are "...dedicated to excellence
      in the development and application of cardiovascular ultrasound to patient care,"
      demands no less.

PMID- 9168350
TI  - Correlation of end-diastolic pressure and myocardial elasticity with the transit
      time of the left atrial pressure wave (A-Ar interval).
AB  - Contraction of the left atrium in diastole generates a pressure wave that moves
      along the postero-lateral wall of the left ventricle (LV), rebounds off the LV
      apex, and is then directed toward the outflow tract. The movement of this atrial
      pressure wave may be detected with pulsed Doppler echocardiography by placing a
      sample volume in the LV outflow tract. The resulting spectral profile shows the
      initial. A velocity wave and also the Ar velocity wave, which is caused by the
      atrial pressure wave rebounding off the LV apex. The transit time from the inflow
      tract to the outflow tract of the atrial pressure wave (A-Ar interval) may be
      determined from the time axis of the spectral profile by measuring the peak-to
      peak separation of the A and Ar, velocity waves. It occurs in the range 25 to 80
      milliseconds. The primary determinant of the A-Ar interval is the elasticity of
      the LV myocardium. We correlated ventricular elasticity with the A-Ar interval in
      47 patients and found a significant negative linear correlation (r = -0.782, p <
      0.001). Because the pressure in a viscoelastic conduit such as the LV is
      determined by the elasticity of the ventricular wall, we correlated end-diastolic
      pressure with the A-Ar interval and again showed a significant negative linear
      correlation (r = -0.701, p < 0.001). The A-Ar interval is an easily measured
      noninvasive index of the diastolic function of the LV that reflects its intrinsic
      elasticity and end-diastolic pressure. It is therefore a quantitative measurement
      of LV wall stiffness and end-diastolic pressure.

PMID- 9168351
TI  - Relationship between atrial function, left ventricular isovolumic relation time,
      and early filling in dual chamber-paced patients.
AB  - This investigation was performed to study atrial systolic function is response to
      modification of atrioventricular delay in a sample of 36 patients with a DDD
      pacemaker implanted for complete atrioventricular block. The relation between
      atrial systolic performance and diastolic-related parameters was also evaluated.
      Isovolumic relaxation time, early diastolic peak velocity, late (atrial)
      diastolic peak velocity, atrial filing fraction, and atrial ejection force were
      recorded at a pacing rate of 70 impulses/min and at atrioventricular delay of
      200, 150, and 100 msec. Our data showed that the progressive shortening of
      atrioventricular delay induced a gradual increase in early peak velocity (median
      value 46 to 53 to 61.5 cm/sec, respectively, at 200, 150, and 100 msec intervals)
      and a gradual decrease in isovolumic relaxation time (median 92.6 to 81.5 to 69.7
      msec at 200, 150, and 100 msec, respectively), atrial peak velocity (59 to 52 to
      44.5 cm/sec at 200, 150, and 100 msec, respectively), atrial filling fraction
      (50.5% to 40% to 23.5% at 200, 150, and 100 msec, respectively), and atrial
      ejection force (17.2 to 14.7 to 8.5 kilodynes at 200, 150, and 100 msec,
      respectively). For every atrioventricular delay value detected, we found a
      significant correlation between isovolumic relaxation time and early peak
      velocity with atrial filling fraction and atrial ejection force. In addition,
      atrial ejection force was related directly to atrial filling fraction at studied
      atrioventricular delays. The two indexes of atrial systolic performance showed a
      parallel decrease by shortening the atrioventricular delay, and they can quantify
      atrial systolic performance equally in sequentially paced patients. Furthermore,
      our results are in accordance with the hypothesis that the interaction between
      the effectiveness of active left atrial emptying and isovolumetric relaxation
      time may play an important role in maintaining an ideal ventricular filling
      despite changes in atrial systolic function.

PMID- 9168352
TI  - Two-dimensional Fourier filtration of acoustic quantification echocardiographic
      images: improved reproducibility and accuracy of automated measurements of left
      ventricular performance.
AB  - To determine the accuracy of Fourier filtration in removing the high-frequency
      component of noise from acoustic quantification (AQ) echocardiographic images, we
      processed 800 parasternal short-axis images obtained from 10 study subjects. M
      mode tracings were also obtained and used as gold standard for correlating the
      results from raw AQ and Fourier-filtered images. Left ventricular short-axis
      diameters measured from the raw AQ and Fourier-filtered data were compared with
      the M-mode diameters (r = 0.91, p < 0.001 for raw AQ; and r = 0.96, p < 0.001,
      for Fourier filtered images). Fractional shortening showed better correlation
      between Fourier-filtered images and M-mode (r = 0.79, p < 0.03) versus raw AQ and
      M-mode (r = 0.33, p = 0.46). Best-to-beat reproducibility was also found to be
      better for fractional area change (r = 0.82, p = 0.01 versus r = 0.66, p = 0.77),
      peak area filling rate (r = 0.87, p = 0.004 versus r = 0.62, p = 0.1), and peak
      are emptying rate (r = 0.99, p < 0.0001 versus r = 0.19, p < 0.7) for Fourier
      filtered versus raw AQ. Our results indicate that Fourier filtration of AQ data
      results in more accurate representation of the true endocardial borders.

PMID- 9168353
TI  - Increased myocardial echo density in left ventricular pressure and volume
      overload in human aortic valvular disease: an ultrasonic tissue characterization
      study.
AB  - Quantitatively assessed ultrasonic backscatter is an index of ultrasonic tissue
      characterization directly related to morphometrically evaluated collagen in human
      beings. Our objective was to assess myocardial reflectivity pattern of patients
      with severe left ventricular hypertrophy caused by either aortic stenosis (AS) or
      aortic regurgitation (AR). Ten patients with AS, 10 patients with AR, and 10
      closely age- and gender-matched healthy controls were studied by two-dimensional
      Doppler echocardiography. By using an echocardiographic prototype, we performed a
      radiofrequency analysis to obtain quantitative operator-independent measurements
      of the integrated backscatter signal of the ventricular septum and the posterior
      wall (integrated backscatter index: IBI, expressed in percentage). All patients
      with stenosis or aortic insufficiency showed a normal regional and global resting
      systolic function (fractional shortening: AS = 36.0 +/- 6.6 versus AR = 40.3 +/-
      6.2 versus control = 40.2 +/- 8.7; p = not significant [NS]) Left ventricular
      mass index (Devereux's formula) was markedly increased in patients with stenosis
      or aortic insufficiency (AS = 199.3 +/- 18 versus AR = 208.8 +/- 60 versus
      control = 97.3 +/- 11 g/m2; p < 0.0001). Myocardial echo density was increased in
      patients with stenosis or aortic insufficiency in comparison with controls, both
      in the septum (IBI%: AR = 40.7 +/- 7.9 versus AS = 33.4 +/- 4.2 versus control =
      23.0 +/- 6.2; p < 0.0001) and in the posterior wall (IBI%: AR = 27.1 +/- 4.3
      versus AS = 23.0 +/- 2.6 versus control = 15.0 +/- 4.2; p < 0.0001). No
      significant correlations were found between septal and posterior wall IBI and
      their thickness. Abnormally increased myocardial echo density--possibly related
      to disproportionate collagen deposition--can be detected in patients with
      pressure or volume overload caused by aortic valve disease and without overt
      systolic dysfunction.

PMID- 9168354
TI  - New semiautomated Doppler method for quantification of volumetric flow:
      intraoperative validation with multiplane transesophageal color Doppler imaging.
AB  - We have validated a new semiautomated method for quantification of volumetric
      flow applied to multiplane transesophageal color Doppler mapping. This Doppler
      technique assumes only the incompressibility of the fluid and includes variations
      of flow area. By computing velocity vectors across a surface normal to the point
      of scanning, volumetric flow can be measured independently of the angle of
      incidence between the ultrasonic beam and the direction of blood flow. Mitral
      valvular flow rate was measured during surgery by transesophageal color Doppler
      echocardiography in 27 patients undergoing coronary artery bypass grafting at 45
      sets of observations. The results were compared with those obtained by the
      thermodilution technique. The mean of the differences between the thermodilution
      technique and color Doppler echocardiography was 0.06 +/- 0.866 L/min for the
      mitral valvular flows (mean of differences [thermodilution-color Doppler] &/- 2
      SDs of differences). Thus mitral valvular volumetric flow measured by this color
      Doppler method showed a close agreement to the thermodilution technique during
      surgery.

PMID- 9168355
TI  - Transthoracic echocardiographic measurement of coronary blood flow and reserve.
AB  - The objectives of this study were to evaluate the use of high-frequency (5 MHz)
      transthoracic echocardiography for the noninvasive measurement of coronary blood
      flow and to test its ability to detect small changes in blood flow that may
      accompany pharmacologic intervention. High-frequency (5 MHz) transthoracic
      echocardiography was performed on the distal segment of the left anterior
      descending coronary artery of 32 consecutive patients (23 men and nine women;
      mean age 60 +/- 10 years) before and after the administration of 0.4 mg
      sublingual nitroglycerin. The results were compared with those of 10 patients
      (eight men and two women; mean age 59 +/- 6 years) in whom the ungrafted left
      internal mammary artery was studied. Doppler velocity profiles of the left
      anterior descending coronary artery were detected in 18 (56%) of the 32 Study
      patients. Left anterior descending coronary artery diameter and blood flow were
      measured in 14 patients (44%). There was no significant difference in blood flow
      between the left anterior descending artery (74 +/- 35 ml/min) and the internal
      mammary artery (52 +/- 25 ml/min). After administration of nitroglycerin, there
      was a 24% decrease in coronary blood flow from 74 +/- 35 ml/min to 56 +/- 30
      ml/min (p < 0.05). This study suggests that high frequency transthoracic
      echocardiography may allow noninvasive identification of the left anterior
      descending coronary artery and detection of small changes in blood flow that
      accompany pharmacologic and mechanical intervention.

PMID- 9168356
TI  - Reproducibility of dobutamine digital stress echocardiography.
AB  - The aim of this study was to investigate the temporal variability and
      interobserver agreement of dobutamine digital stress echocardiography. We
      performed two dobutamine stress echocardiographic studies (dobutamine up to 40
      micrograms/kg/min and atropine up to 1 mg) in 15 patients with previous
      myocardial infarction at a mean of 19 days apart. Two observers assessed the wall
      motion using a six-point score in a 16-segment model and calculated the wall
      motion score index at rest and at peak stress by using a quad screen display.
      Analysis of the wall motion was performed separately on the day after each
      dobutamine stress test (analysis A), and all images from the serial studies in
      the same patient were simultaneously retrieved and compared side-by-side in the
      same view (analysis B). The mean values of heart rate and blood pressure were
      comparable for each in the two studies except for the heart rate at rest.
      Regarding the presence and absence of positive findings of dobutamine stress
      echocardiography, interobserver agreement was 93% (70% to 99% with 95% confidence
      limits, kappa value 0.86) in the patients and 93% (70% to 99% with 95% confidence
      limits, kappa value 0.80) in the three major vascular regions with the use of
      analysis A. these values did not improve with the use of analysis B. The
      agreement of the temporal variability was 93% (70% to 99% with 95% confidence
      limits, kappa value 0.86) in the patients and 84% (71% to 92% with 95% confidence
      limits, kappa value 0.66) in the vascular regions with the use of analysis A.
      These values further improved with the use of analysis B. With the comparison of
      the wall motion score index, interobserver variability showed a correlation
      coefficient of 0.88 at rest and 0.90 at peak stress with analysis A and 0.78 and
      0.82, respectively, with analysis B. Corresponding analysis of temporal
      variability showed correlation coefficients of 0.99 at rest and 0.99 at peak
      stress when both analysis were used. Although dobutamine digital stress
      echocardiography has good reproducibility and negligible interobserver
      variability, even if the digital quad screen format is used, it requires strict
      standardization of the reading criteria and the objective measurements of wall
      motion in the expansion of this test to the evaluation of the changes in left
      ventricular function during more than two serial studies in the same patient.

PMID- 9168357
TI  - Intracardiac ultrasound detection of right ventricular infarction in a canine
      model.
AB  - Our objective was to demonstrate that right ventricular (RV) infarction could be
      demonstrated by intracardiac ultrasonography in a canine model. RV infarction is
      a common and important clinical condition in patients with myocardial infarction.
      Traditional methods for diagnosing RV infarction have limitations. Intracardiac
      echocardiography, in which an ultrasonic transducer on the tip of a catheter is
      placed intravenously into the RV chamber, should allow detection of RV
      infarction. Nine closed-chest dogs were studied. The animals were instrumented
      with a 10 MHz ultrasound catheter placed into the right ventricle. The right
      coronary artery was occluded with a balloon angioplasty catheter for 20 minutes
      and subsequently embolized with elemental mercury. Intracardiac ultrasound images
      were obtained at baseline, during balloon occlusion, and during embolization. RV
      cross-sectional end-diastolic and end-systolic areas were calculated and
      fractional area changes were calculated; RV wall motion abnormalities were also
      evaluated. The interventricular septal thickening was also calculated. The 10 MHz
      intracardiac ultrasound catheter allowed visualization of much of the RV chamber
      and interventricular septum. The RV cross-sectional area increased with mercury
      embolization, which was also associated with regional wall motion abnormalities.
      RV end-systolic area was 1.6 cm2 and end-diastolic area 3.9 cm2 at baseline;
      these increased to 4.8 cm2 and 6.5 cm2 after embolization (p < 0.05).
      Interventricular septal thickening remained unchanged. The echocardiographic
      features of RV infarction, which include RV dilation and RV regional wall motion
      abnormalities, could be demonstrated in a canine infarct model with a 10 MHz
      intracardiac ultrasound catheter.

PMID- 9168359
TI  - Occupational health hazards to the ultrasonographer and their possible
      prevention.
AB  - Occupational health hazards in ultrasonography are becoming more prevalent as the
      field continues to grow. Eye strain, musculoskeletal pain or injury, carpal
      tunnel syndrome, repetitive strain injuries, stress, burnout, and other hazards
      have been addressed as concerns in other studies and surveys. These topics are
      discussed, as well as the possible preventive measures that may be used to
      maximize and maintain the ultrasonographer's well-being throughout his or her
      career.

PMID- 9168358
TI  - Musculoskeletal pain in cardiac ultrasonographers: results of a random survey.
AB  - Myalgias and arthralgias are common among workers whose jobs require repetitive
      isometric maneuvers or malalignment of body position. However, few systematic
      studies have been performed to evaluate the frequency of these complaints among
      cardiac ultrasonographers. Therefore the purpose of this study was to determine
      the prevalence of musculoskeletal pain (MSP) among ultrasonographers and to
      identify risk factors related to their occurrence. Two hundred twenty
      ultrasonographers randomly chosen from a list of more than 1600 active members of
      the American Society of Echocardiography were mailed surveys consisting of 22
      questions. Included were questions regarding height, age, years of experience,
      frequency and type of physical exercise, and job-related parameters such as a
      number of scans per day, scanning from right or left side of bed, number of
      hours, bed type, type of equipment, and manual or self-propelled machines.
      Respondents were asked whether they had had back, neck, or shoulder pain related
      to their profession and to describe treatment rendered and its effectiveness. One
      hundred thirteen (51%) of 220 ultrasonographers responded to the survey. Ninety
      (80%) of 113 respondents reported new pain that was not present before they began
      scanning, with 42 of this group (46%) requiring either physiotherapy (n = 17) or
      medication (n = 23). Treatment was believed to be helpful in 63% of cases.
      Factors found to have a positive relationship to MSP included ultrasonographer
      height less than 63 inches, performing 100 or more scans per month, average scan
      time of 25 minutes or more per patient, and use of manually propelled machines
      (each p < 0.05). Factors found to have no relationship to MSP included age, type
      of equipment, right or left scan position, physical conditioning, bed type, and
      time between patients. Musculoskeletal pain is prevalent among cardiac
      ultrasonographers, and may have specific work-related factors for its occurrence.

PMID- 9168360
TI  - Gonococcal endocarditis: assessment by transesophageal echocardiography.
AB  - Gonococcal endocarditis is a rare but aggressive infection that has an alarming
      rate of perivalvular abscess and mortality. We present a case of gonococcal
      endocarditis with intracardiac abscess and fistula diagnosed by transesophageal
      echocardiography. Given the often acute nature of gonococcal endocarditis and its
      propensity toward abscess formation, transesophageal echocardiography should be
      considered early in the course of this infection.

PMID- 9168361
TI  - A rare cause of late infective endocarditis after heart surgery.
AB  - A case is reported of a male patient with rheumatic mitral valve disease and open
      mitral valve commissurotomy, performed 13 years before, who had fever and
      multiple septic embolic events. Serial blood cultures were positive for
      Pseudomonas aeruginosa. Transthoracic and transesophageal echocardiography
      demonstrated the presence of an irregular, round, very mobile mass inserted in
      the fossa ovalis region of the interatrial septum. After resolution of the
      infectious process, surgery was performed. The structure previously described
      corresponded to a elongated suture material covered by fibrin. It had been
      secondarily infected and it was the cause of the entire process.

PMID- 9168362
TI  - Transesophageal echocardiographic detection of complications after Cabrol's
      procedure.
AB  - Cabrol's procedure represents an improvement on earlier surgical techniques used
      in the management of a patient with aortic insufficiency associated with an
      aneurysm of the ascending aorta. We report a patient in whom the diagnosis of
      complications after a Cabrol procedure was facilitated by transesophageal
      echocardiography. The role of transesophageal echocardiography in the follow-up
      of these patients is discussed.

PMID- 9168363
TI  - Traumatic pseudoaneurysm of the left sinus of Valsalva: a case report.
AB  - Deceleration injuries of the aorta result in tears that often lead to
      exsanguinating hemorrhage. The site is most often at the aortic isthmus, with
      injuries of the aortic root being rare. A minority of patients survive long
      enough to reach the hospital where prompt diagnosis and treatment are essential
      for survival. We hereby report on a patient who had a pseudoaneurysm of the left
      sinus of Valsalva 13 years after a deceleration accident, presumably caused by a
      contained rupture of the aortic root. Transesophageal echocardiography was of
      great value in studying the features of the pseudoaneurysm and its relation to
      the left main coronary artery and left upper pulmonary vein.

PMID- 9168364
TI  - Left atrial myxoma presenting with embolism to the aorta.
AB  - We present a patient with left atrial myxoma embolizing to the ascending aorta.
      The features have not been reported previously and were diagnosed with
      transesophageal echocardiography.

PMID- 9168365
TI  - Multiplane transesophageal echocardiography to detect effectiveness of selective
      pulmonary recombinant tissue-type plasminogen activator thrombolysis in pulmonary
      embolism and patent foramen ovale.
AB  - A functionally patent foramen ovale can create a relevant right-to-left shunt
      during massive pulmonary embolism. This associated feature, although maintaining
      adequate cardiac output, may explain both the paradoxic embolism and the
      uneffectiveness of peripherally administered drugs. This case demonstrates the
      potential of transesophageal echocardiography in monitoring the hemodynamic
      findings of such patients and, consequently, the effectiveness of thrombolytic
      treatment.

PMID- 9168366
TI  - Cyclic vs continuous enteral feeding with omega-3 and gamma-linolenic fatty
      acids: effects on modulation of phospholipid fatty acids in rat lung and liver
      immune cells.
AB  - Arachidonic acid (AA) present in lung and liver immune cell phospholipids is the
      precursor of eicosanoids that promote neutrophil margination, leading to tissue
      injury and inflammation. Administration of novel enteral formulations low in
      linoleic acid (LA) and containing eicosapentaenoic acid (EPA) from fish oil and
      gamma-linolenic acid (GLA) from borage oil displaces AA and promotes cell
      formation of eicosanoids with reduced inflammatory potential. The present study
      was undertaken to determine whether or not short-term provision of enteral diets
      containing GLA, EPA, or both in a cyclic fashion modulated the fatty acid
      composition of rat alveolar macrophage (AM) and liver Kupffer and endothelial
      (K&E) cell phospholipids in vivo to the extent achieved during continuous
      feeding. METHODS: Rats were isocalorically fed through a gastrostomy catheter for
      3 or 6 days with high-fat, low-carbohydrate diets that were enriched with either
      LA (diet A), EPA (diet B), or EPA + GLA (diet C). The rats were randomized by
      infusion modality, ie, continuous vs cyclic (14 hours feeding with 10 hours
      fasting daily) feeding. AM and K&E were isolated and phospholipid fatty acid
      profiles were determined by gas chromatography. RESULTS: The dietary effects on
      AM and K&E cell phospholipid fatty acids for a given feeding period were not
      significantly influenced by the infusion modality. AM and K&E cells from rats
      receiving either diet B or diet C for 3 days had significantly lower AA and LA
      and higher EPA and dihomo-GLA (DHGLA), respectively, than rats given diet A
      regardless of the infusion modality. The mole % of EPA and DHGLA in K&E cells
      were higher after 6 vs 3 days of cyclic feeding with diet C. Using the eicosanoid
      precursor ratio (EPA + DHGLA/AA), the potential for generation of AA-derived
      eicosanoids was lower in rats given die B or C vs diet A regardless of infusion
      modality. DISCUSSION: Given the rapid changes in lung and liver immune cell
      phospholipid fatty acids, short-term provision of EPA and GLA-enriched diets
      cyclically or continuously may prove clinically relevant for modulating the fatty
      acid composition and potential eicosanoid formation by these cells.

PMID- 9168367
TI  - Nutrition support in clinical practice: review of published data and
      recommendations for future research directions. National Institutes of Health,
      American Society for Parenteral and Enteral Nutrition, and American Society for
      Clinical Nutrition.
AB  - In the last 30 years, marked advances in enteral feeding techniques, venous
      access, and enteral and parenteral nutrient formulations have made it possible to
      provide nutrition support to almost all patients. Despite the abundant medical
      literature and widespread use of nutritional therapy, many areas of nutrition
      support remain controversial. Therefore, the leadership at the National
      Institutes of Health, The American Society for Parenteral and Enteral Nutrition,
      and The American Society for Clinical Nutrition convened an advisory committee to
      perform a critical review of the current medical literature evaluating the
      clinical use of nutrition support; the goal was to assess our current body of
      knowledge and to identify the issues that deserve further investigation. The
      panel was divided into five groups to evaluate the following areas: nutrition
      assessment, nutrition support in patients with gastrointestinal diseases,
      nutrition support in wasting diseases, nutrition support in critically ill
      patients, and perioperative nutrition support. The findings from each group are
      summarized in this report. This document is not meant to establish practice
      guidelines for nutrition support. The use of nutritional therapy requires a
      careful integration of data from pertinent clinical trials, clinical expertise in
      the illness or injury being treated, clinical expertise in nutritional therapy,
      and input from the patient and his/her family.

PMID- 9168368
TI  - A double-blind randomized trial comparing outpatient parenteral nutrition with
      intravenous hydration: effect on resumption of oral intake after marrow
      transplantation.
AB  - BACKGROUND: Outpatient parenteral nutrition (PN) is often given to marrow
      transplant recipients after high-dose chemoradiotherapy until the resumption of
      adequate oral intake; however, it may adversely prolong resumption or oral
      calorie intake by contributing to early satiety. METHODS: A double-blind,
      randomized study compared standard PN (final concentration 25% dextrose, 5% amino
      acids) with a hydration solution (5% dextrose) during the first 28 days of
      outpatient treatment. Patients were eligible for the study if they were > or = 2
      years of age, < 65 days posttransplant, had < 70% oral caloric intake at hospital
      discharge, and required < or = 10 U insulin/L PN. Solutions were provided until
      the patient's oral intake met > or = 85% caloric requirements for 3 consecutive
      days. RESULTS: Two hundred fifty-eight marrow transplant recipients (128, PN and
      130, hydration solution) were studied. Age, donor type, and diagnoses were
      similar in the two groups. Time to resumption of > or = 85% oral caloric intake
      was 6 days sooner in the hydration group than in the PN group (median 10 vs 16
      days, respectively; p = .049). When adjusting for sex, age, donor type, total
      body irradiation, previous oral intake, acute graft-versus-host disease, and
      prednisone therapy, the hydration group resumed oral intake sooner than the PN
      group (relative risk = 1.51; 95% confidence interval [CI] 1.04 to 2.19; p =
      .029). The percentage of weight change from pretransplant values, adjusted for
      the above covariates and the number of weeks of treatment, indicated that the
      hydration solution group lost weight (4.63%) compared with the PN group (1.27%)
      after 4 weeks of therapy (p = .004). Rates of hospital readmissions, relapse of
      malignancy, and survival did not differ between the two treatment groups.
      CONCLUSIONS: We conclude that outpatient PN delays resumption of oral intake and
      that its replacement with hydration solution does not result in adverse patient
      outcome.

PMID- 9168369
TI  - Effects of small-peptide and whole-protein enteral feedings on serum proteins and
      diarrhea in critically ill patients: a randomized trial.
AB  - BACKGROUND: It has been proposed that enteral feeding formulas containing small
      peptides are more efficacious and better tolerated than whole-protein formulas in
      critically ill patients. METHODS: Intensive care unit patients were stratified
      with regard to treatment with antibiotics and serum albumin and randomized to
      treatment with a small-peptide enteral diet or an isoenergetic, isonitrogenous
      whole-protein diet for 10 days. To assess efficacy, we measured serum prealbumin
      and fibronectin, and to assess tolerance, we monitored the incidence of diarrhea.
      A protocol was followed to ascertain all causes of diarrhea (defined as > 200 g
      stool or > or = 3 liquid stools on 2 consecutive days). RESULTS: Fifty subjects
      completed the trial. Serum prealbumin and fibronectin increased between 21% and
      36% in both groups, but the increase was significant only in the small-peptide
      group. The change in fibronectin between days 5 and 10 was significantly greater
      in the small-peptide group (p = .02). Diarrhea occurred in 10 subjects (17.8% of
      days) receiving small-peptide feeding and 4 subjects (7.5% of days) receiving
      whole-protein feeding (P = .07 for incidence and 0.03 for prevalence), but the
      difference was explained by the coincidental use of more diarrhea-causing
      medications in the former. Only one case of diarrhea could be attributed to tube
      feeding. CONCLUSIONS: During 10 days of feeding, the small-peptide diet produced
      slightly greater increases in serum rapid-synthesis proteins than did the whole
      protein diet, especially between days 5 and 10. The clinical implications of this
      difference between the diets are unknown. Both small-peptide and whole-protein
      diets were well tolerated.

PMID- 9168370
TI  - Accuracy of 30-minute indirect calorimetry studies in predicting 24-hour energy
      expenditure in mechanically ventilated, critically ill patients.
AB  - BACKGROUND: There is no consensus regarding the optimal duration of measurement
      or time of day to perform indirect calorimetry (IC). Energy expenditure (EE)
      varies at different times of day and with different activity levels. We sought to
      assess the variability of EE in mechanically ventilated patients over a 24-hour
      period and the accuracy of 30-minute IC studies in predicting the 24-hour energy
      expenditure (EE24). METHODS: The study was a prospective comparison between the
      resting EE obtained by 30-minute measurement of IC and EE values obtained from 24
      hour measurements. Tests were performed in the Medical Intensive Care Unit (MICU)
      of a tertiary care, university hospital. Oxygen consumption (VO2) and carbon
      dioxide production (VCO2) were measured for 24 hours in eight ventilated
      patients. Measurements were made every 3 minutes and used to calculate 30-minute
      and 24-hour oxygen consumption values. EE24 was calculated using the modified
      Weir equation. Each 30-minute interval was compared with the value obtained from
      the 24-hour measurement. RESULTS: Three hundred forty-one of 384 30-minute
      intervals remained for analysis. Average EE24 measured was 1490 +/- 486 kcal/d.
      Average EE24 predicted by extrapolation from 30-minute studies was 1501 +/- 503
      kcal/d, with a mean difference of 0 +/- 209 kcal/d from the measured 24-hour
      values (range: -1068 to +585 kcal/d). Thirty-minute studies were within 20% of 24
      hour measurements for 89% of intervals. The difference between 24-hour and 30
      minute studies correlated with changes in minute ventilation (VE), heart rate,
      systolic blood pressure, and breath rate from their 24-hour means (p < .001). The
      mean error of EE estimate was greatest between 3 and 11 PM (p < .001).
      CONCLUSIONS: We conclude the following: (1) EE in MICU patients is variable; (2)
      30-minute IC studies predict measured EE24 acceptably well for clinical purposes;
      and (3) accuracy is maximized if a 30-minute study is performed between 11 PM and
      3 PM, and when Ve, heart rate, systolic blood pressure, and breath rate are near
      the day's average.

PMID- 9168371
TI  - Enhanced growth of small bowel in transgenic mice expressing human insulin-like
      growth factor 1.

PMID- 9168372
TI  - Dose-response effect of butyrate.

PMID- 9168373
TI  - Re-evaluation of oral contraceptive classifications.
AB  - Classification of combination oral contraceptives (OCs) by "generation"-
      typically based on the time of introduction of new compounds--is problematic. The
      estrogen and progestin components may be present in differing doses, and their
      interaction may therefore vary from one formulation to another. In addition,
      assigning the progestin component itself to a particular generation does not
      account for the unique characteristics of individual progestins within that
      group. These issues can be clarified by understanding the evolution of
      combination OCs in relation to dosage changes and by differentiating the
      pharmacologic profiles of individual progestins, particularly norgestimate,
      desogestrel, and gestodene. Although all sex steroids have the same basic
      structure, relatively minor structural modifications can cause dramatic
      alterations in biochemical activity. Progestational activity is the desired
      pharmacologic effect of progestins used in OCs, whereas androgenic activity,
      which increases the potential for adverse metabolic and physical side effects, is
      undesired. In vitro assays of the ability of various OC progestins to bind
      progestin and androgen receptors suggest that the androgen/progestin (A/P)
      binding ratio--a measure of progestin selectivity--is more favorable for
      norgestimate than for levonorgestrel, gestodene, or desogestrel. In vivo
      measurements of interactions between various progestins and human sex hormone
      binding globulin (SHBG) support the concept that generational classification of
      OC progestins is misleading. These compounds also differ clinically, as
      exemplified by differential effects on lipoprotein metabolism. In summary,
      progestins exhibit individually unique biochemical and clinical properties.

PMID- 9168374
TI  - The estrogen component of OCs: cardiovascular benefits and risks.
AB  - The relationship of oral contraceptive (OC) use to risk of venous thrombolism,
      stroke, and myocardial infarction continues to be evaluated. The estrogen
      component of combination OCs, which is primarily responsible for maintaining the
      endometrium and minimizing breakthrough bleeding (BTB) and spotting, was the
      initial focus of clinical and epidemiologic interest following early reports of
      an increased risk of vascular events with high-estrogen-dose formulations. OC
      estrogen continues to hold attention; current areas or interest include the
      relationship of estrogen to laboratory changes in hemostatic, lipid/lipoprotein,
      and carbohydrate variables, and, more important, to their possible clinical
      consequences. The historical view that OC-induced lipoprotein changes are
      responsible for observed increases in vascular risk in OC users is being debated,
      but the preponderance of evidence suggests that CO-related vascular disease is
      most likely due to thrombosis rather than atherosclerosis. This issue is made
      somewhat moot, however, by cumulative epidemiologic data indicating that although
      some combination OCs containing < or = 35 micrograms estrogen appear to produce a
      slight increase in the risk of venous thromboembolism, they have no adverse
      effect on the risk of myocardial infarction and minimal, if any, effect on the
      risk of stroke. The risks that may be associated with cigarette smoking and
      concomitant OC use have recently emerged as a somewhat contested issue relative
      to estrogen dose. Critical examination of the available information suggests that
      women over 35 years of age who smoke should be advised to use non-estrogen
      contraceptive methods and that smokers under age 35 may use any OC containing <
      50 micrograms estrogen.

PMID- 9168375
TI  - OC practice guidelines: minimizing side effects.
AB  - The side effects of oral contraceptives (OCs) can be minimized by appropriate OC
      selection. Side effects or perceived side effects that manifest themselves
      physically--e.g., weight gain, breakthrough bleeding (BTB), nausea, headache,
      breast tenderness, mood swings, acne, and hirsutism--are the most common causes
      of premature discontinuation of oral contraception. The relative androgenicity of
      the progestin component of combination OCs has become an important differential
      in selecting OC formulations. Several studies have indicated that preparations
      with less androgenic potential can minimize some of the "physical" side effects
      and adverse metabolic effects traditionally associated with oral contraception.
      Acne and hirsutism, common pre-existing conditions that are clearly related to
      the androgenicity of the progestin component, can be eliminated or improved by
      use of OCs with low androgenic activity. Many women perceive that OCs cause
      weight gain; although weight gain is to some extent androgen related, most
      studies comparing low-androgenic OCs with medium- or high-androgenic preparations
      have found little or no change in weight regardless of formulation. BTB, which
      usually subsides within a few months, is related to the dose, potency, and ratio
      of the estrogen and progestin in the OC formulation. Low-estrogen-dose OCs (< or
      = 35 micrograms ethinyl estradiol [EE]) containing less androgenic progestins are
      associated with bleeding patterns as acceptable as older low-estrogen-dose
      formulations. The same analysis found that smoking cigarettes promotes BTB in
      women who use OCs. There is no convincing evidence that the use of one progestin
      or another is less likely to cause or exacerbate headache; however, changing
      preparations sometimes reduces the incidence. Women with persistent headaches
      during the pill-free interval may benefit from a longer cycle of OC treatment.
      Nausea and breast tenderness are primarily estrogen-related effects; if a women
      experiences persistent nausea, switching to an OC formulation containing 20
      micrograms EE may be appropriate as long as the patient is cautioned that BTB is
      more likely. Mood changes are a common, highly subjective complaint whose
      relationship to OC use is hard to assess. Concerns about the potentially
      deleterious effects of combination OCs on lipid/lipoprotein and carbohydrate
      metabolism have been substantially diminished by new epidemiologic findings
      relative to cardiovascular disease as well as by the development of low
      androgenic progestins. Formulations containing these progestins lower LDL
      cholesterol and increase HDL cholesterol; they do not affect carbohydrate
      metabolism as much as older, more androgenic formulations.

PMID- 9168376
TI  - Thrombophilic mechanisms of OCs.
AB  - Oral contraceptives (OCs) have minor effects on procoagulant and anticoagulant
      factors. Clotting factor changes that are associated with the use of low
      androgenic OCs include a 10% to 20% increase in fibrinogen, variable effects on
      factor VII, an increase in fibrinopeptide A, and a 10% to 20% decrease in protein
      S (in comparison, levels of protein S decrease approximately 70% during
      pregnancy). Although these acquired changes can be statistically significant
      between OC users and nonusers, there is no evidence that they are clinically
      significant. In contrast, increased risk of venous thrombosis has been associated
      with inherited deficiencies in protein S and protein C, which are both natural
      anticoagulant proteins. In addition, activated protein C (APC) resistance can
      occur via a mutation of factor V, known as factor V Leiden, which is present in
      5% of the general population and 20-40% of patients with venous thrombosis. In
      one study, the combination of OC use and factor V Leiden positivity was
      associated with a 35-fold increased risk of venous thrombosis compared with
      controls. However, the absolute risk of venous thrombosis in this group was low;
      the incidence of venous thrombosis was 28.5 events per 10,000 women-years in
      women with both factors (in comparison, pregnancy was associated with an
      incidence of 5.9 per 10,000 women-years). Even if venous thrombosis could be
      totally prevented in OC users with the Leiden mutation, there would be little
      impact on the total number of cases of venous thrombosis; therefore, routine
      screening for factor V Leiden or APC resistance prior to starting women on OCs
      does not seem to be warranted.

PMID- 9168377
TI  - Homelessness and adolescents.

PMID- 9168378
TI  - Trichotillomania and anorexia nervosa.

PMID- 9168379
TI  - Risk of primary cytomegalovirus infection during pregnancy according to maternal
      age.

PMID- 9168380
TI  - A study of HIV seroprevalence in a group of homeless youth in Hollywood,
      California.
AB  - The objective of this descriptive-exploratory study was to examine the HIV
      seroprevalence rate among a sample of homeless youth in Hollywood, California. A
      total of 96 respondents (age 14-24) were administered a questionnaire and had
      their blood drawn to test for the presence of HIV antibodies, during nightly
      street outreach activities conducted by Covenant House California. The HIV
      seroprevalence rate was 11.5% for the sample. Chi-square analysis showed strong
      correlation between HIV status and sexual risk behavior but not for HIV status
      and drug-related risk behavior.

PMID- 9168381
TI  - A risk profile of street youth in northern California: implications for gender
      specific human immunodeficiency virus prevention.
AB  - PURPOSE: To assess human immunodeficiency virus (HIV) risk behaviors of street
      youth and to determine whether risk behaviors differ by gender or housing status.
      METHODS: Using systematic street-based sampling in four Northern California
      cities, we recruited 429 street youth (mean age = 19.2 years). Participants
      completed a structured interview which was used to assess sexual and drug HIV
      risk behaviors. RESULTS: The majority of youth were heterosexual (85%), white
      (77%), male (68%), and currently without any type of stable housing (75%).
      Although 60% of the sample had had vaginal sex in the past 30 days, only 44% used
      a condom the last time they had sex. About one-third (32%) of the sample reported
      ever injecting drugs, and almost all reported lifetime use of multiple drugs
      including D-lysergic acid diethylamide (96%), marijuana (90%), alcohol (81%),
      cocaine (70%), and speed (70%). Compared to males, females were equally likely to
      use injection and noninjection drugs, but were more likely to be sexually active
      (P < .001), were more likely to have been diagnosed with a sexually transmitted
      disease (P = .005), and were less likely to report consistent condom use (P =
      .003) or intent to use condoms consistently in the future (P = .005). Compared
      with those with stable housing, youth who were currently without such housing
      reported higher rates of injection, and other drug use; females without stable
      housing were less likely to have used condoms the last time they had vaginal
      intercourse. CONCLUSION: The high level of HIV risk behavior in this street-based
      sample of youth, particularly females and youth without stable housing, suggests
      an urgent need for gender-specific prevention efforts and an increased range of
      housing options.

PMID- 9168382
TI  - Health beliefs and intention to get immunized for HIV.
AB  - PURPOSE: The purpose of this study was to evaluate the relationship of health
      beliefs to intention to accept human immunodeficiency virus (HIV) vaccination.
      METHODS: Respondents were 81 female and 44 male college students who completed
      self-administered questionnaires. Questionnaires included items assessing
      intention to get vaccinated for HIV and the following health beliefs: perceived
      susceptibility to HIV infection, severity of AIDS, benefits of HIV immunization,
      pragmatic obstacles to vaccination, conditional nonmembership in a risk group,
      fear of the vaccine, and fear of needles. RESULTS: Nearly 30% of the subjects
      were uncertain about or opposed to getting immunized for HIV. Susceptibility,
      severity, pragmatic obstacles, conditional nonmembership in a risk group, and
      fear of the vaccine were significantly correlated with intent to get vaccinated.
      Fear of needles, gender, and race were not associated with intent to get an HIV
      vaccine. Multiple regression analysis identified susceptibility, benefits,
      pragmatic obstacles, nonmembership in risk group, and fear of the vaccine as
      significant independent predictors of intent to vaccinate. CONCLUSIONS: These
      preliminary survey findings demonstrate that intention to accept HIV immunization
      is not universal and that health beliefs may influence HIV vaccine acceptance.
      They suggest that it may be important to consider the effects of psychological
      factors in future research on HIV vaccine acceptance and in the ultimate
      implementation of HIV immunization programs.

PMID- 9168383
TI  - Homeless youth and their exposure to and involvement in violence while living on
      the streets.
AB  - PURPOSE: The purpose of this research were to explore homeless youths' histories
      of exposure to violence, perpetration of violence, and fear of violent
      victimization, and to examine the extent to which these constructs are associated
      with demographic variables. METHODS: A sample of 432 youth (between 13 and 23
      years old) who were homeless or at imminent risk for homelessness were sampled
      from both service and street sites. The percentage of youth who reported exposure
      to each type of violence was calculated. Multiple regression analyses were used
      to examine differences in the risk of exposure to violence across gender,
      ethnicity, age, and length of time homeless. RESULTS: Respondents reported a high
      rate of exposure to violence. Female respondents reported levels of exposure to
      violence that were as high as those reported by males. Females were more likely
      to report having been sexually assaulted and fearing victimization, and tended to
      be less likely to report perpetrating violence. With a few exceptions, ethnic
      identity was not a significant predictor of exposure to violence or fear of
      victimization. Age tended to be inversely associated with risk of exposure to
      violence. Length of time homeless was not associated with fear of victimization.
      CONCLUSIONS: Homeless youth are at high risk for exposure to a variety of forms
      violence as both witnesses and victims. The overall rates of exposure to violence
      and patterns of association with demographic variables are significantly higher
      than those reported in national samples of adolescents.

PMID- 9168384
TI  - Adolescents' exposure to community and school violence: prevalence and behavioral
      correlates.
AB  - PURPOSE: The purpose of this research was to study adolescents' perceptions of
      violence in their communities and schools and examine the relationship between
      these reports and their emotional and behavioral functioning, controlling for the
      effects of family violence and other sociodemographic variables. METHODS:
      Respondents included 935 urban and suburban high school students who completed
      the Youth Self-Report (YSR) as well as measures assessing their perceptions of
      community, school, and family violence. RESULTS: This sample of high school
      students was exposed to high levels of violence in their communities and schools.
      Over 45% of the students reported witnessing severe forms of violence such as a
      shooting or stabbing in their communities or schools during the year prior to the
      study. Hierarchic regression analyses revealed that for males, exposure to
      community and school violence was a significant predictor of aggressive acting
      out behaviors, even when controlling for the effects of family violence and other
      sociodemographic variables. For girls, only exposure to school violence was a
      significant predictor of aggression. The results for internalizing scores
      (depression, withdrawal) were less impressive, particularly for males.
      CONCLUSIONS: The high levels of violence exposure of adolescents in their
      communities and schools and the associated increase in behavior problems suggest
      the need for developing school and community intervention programs to treat
      violence and its impact.

PMID- 9168385
TI  - The association of sexual risk behaviors and problem drug behaviors in high
      school students.
AB  - PURPOSE: To examine the associations among early age of onset of sexual
      intercourse and drug use, lifetime and current problem drug behaviors, and sexual
      risk behaviors. METHODS: The 1993 Massachusetts Youth Risk Behavior Survey was
      administered to a sample of 3,054 students from randomly selected high schools
      and classrooms; 36% (1,078) consistently reported having had sexual intercourse.
      Three indicators of sexual risk behaviors were assessed: (1) number of lifetime
      sexual partners, (2) number of recent partners, and (3) condom nonuse at last
      intercourse. Three sets of independent variables were analyzed: (1) age of onset
      of sexual intercourse and drug use, (2) lifetime drug use, and (3) recent drug
      use. RESULTS: Years of sexual intercourse, early age of onset of marijuana and
      cocaine use, lifetime frequency of marijuana, crack/freebase cocaine and alcohol
      use, and black race accounted for moderate amounts of the variation in the number
      of lifetime sexual partners. Years of sexual intercourse, early age of onset of
      marijuana use and cocaine use, lifetime frequency of crack/freebase and marijuana
      use, and recent use of cocaine, alcohol, and cigarettes accounted for smaller but
      significant amounts of the variation in the number of recent partners. Students
      more likely to report recent condom nonuse were older, females, had more years of
      sexual intercourse, had tried cocaine at a younger age, had used marijuana and
      cocaine more times (lifetime), and had more frequent recent use of marijuana.
      CONCLUSION: Increased frequency and severity of drug use behaviors and more years
      of sexual intercourse are associated with an increased number of sexual partners
      and recent condom nonuse. These findings may guide history-taking and referral
      practices of health care providers. Programs designed to prevent sexually
      transmitted diseases and pregnancy should address drug use as well as sexual
      behavior.

PMID- 9168386
TI  - Preteenage drug use in Australia: the key predictors and school-based drug
      education.
AB  - PURPOSE: The promise that early intervention school-based drug education is it
      will have public health benefits. This argument was explored through identifying
      the key predictors of early adolescent social drug use. METHODS: A cross
      sectional survey involving 3,019 6th year students, aged 11-12 years
      (participation rate: 99%), enrolled in 86 Melbourne primary schools was carried
      out to determine students' social drug use. In addition data were collected on
      known key social, personal, and education predictors. Logistic regression was
      used to identify significant predictors of drug experimentation and use. RESULTS:
      The key predictors of girls' tobacco use were friends' smoking (OR: 6.7), low
      literacy (OR: 4.4), and alcohol use (OR: 3.9). For boys they were friends'
      smoking (OR: 8.6), low literacy (OR: 4.2), and alcohol use (OR: 3.1). For alcohol
      use, the key predictors for girls were smoking (OR: 4.2), parents' drinking (OR:
      3.9), and friends' drinking (OR: 3.8). For boys they were friends' drinking (OR:
      3.3), smoking (O: 2.8), and poor literacy (OR: 2.6). Regarding analgesic use, for
      girls the key predictors were alcohol use (OR: 3.3), analgesic self
      administration (OR: 2.4), and parents' drinking or working as
      tradespersons/laborers (OR: 1.7, respectively). For boys they were analgesic self
      administration (OR: 2.5), drinking (OR: 1.9), smoking (OR: 1.7). CONCLUSIONS: The
      key predictors of social drug use--which suggests multiple recruitment pathways-
      were all outside the ambit of drug education programs. The impact of education on
      recruitment to drug use or experimentation among the young is therefore likely to
      be slight.

PMID- 9168387
TI  - Promoting health and preventing disease: an international perspective on youth
      health promotion.
AB  - PURPOSE: To advocate strategies to promote the health of young people that
      include action to create supportive social and economic conditions, alongside
      more traditional actions to strengthen individual capacity to protect health.
      METHODS: Analysis of different strategies for youth health promotion from
      different countries, including education, public policies, laws, and regulations
      that protect young people from exploitation and physical harm, and enhance their
      capacity to make healthy lifestyle choices. RESULTS: Access to education and the
      promotion of basic literacy are, in their own right, important public health
      goals. Beyond this, efforts to promote health through schools should focus on the
      creation of an integrated and mutually reinforcing set of experiences for young
      people, including classroom health education, the creation of a safe and healthy
      physical environment, and provision of appropriate school health services. The
      creation of supportive social and economic conditions are also essential, and
      require political action through the development of public policy. Such policies
      include restricting access to tobacco, alcohol, and illicit drugs, improving
      access to essential health services; and regulation of economic exploitation of
      young people. CONCLUSIONS: Health promotion is inherently political. Health
      professionals have to find ways to become more effective political advocates for
      young people. This should be reflected in the education of health professionals
      and educators, and in the work of agencies and professional associations.

PMID- 9168389
TI  - Combined solution of the inverse Stefan problem for successive freezing/thawing
      in nonideal biological tissues.
AB  - A new combined solution of the one-dimensional inverse Stefan problem in
      biological tissues is presented. The tissue is assumed to be a nonideal material
      in which phase transition occurs over a temperature range. The solution includes
      the thermal effects of blood perfusion and metabolic heat generation. The
      analysis combines a heat balance integral solution in the frozen region and a
      numerical enthalpy-based solution approach in the unfrozen region. The subregion
      of phase transition is included in the unfrozen region. Thermal effects of blood
      perfusion and metabolic heat generation are assumed to be temperature dependent
      and present in the unfrozen region only. An arbitrary initial condition is
      assumed that renders the solution useful for cryosurgical applications employing
      repeated freezing/thawing cycles. Very good agreement is obtained between the
      combined and an exact solution of a similar problem with constant thermophysical
      properties and a uniform initial condition. The solution indicated that blood
      perfusion does not appreciably affect either the shape of the temperature forcing
      function on the cryoprobe or the location and depth of penetration of the
      freezing front in peripheral tissues. It does, however, have a major influence on
      the freezing/thawing cycle duration, which is most pronounced during the thawing
      stage. The cooling rate imposed at the freezing front also has a major inverse
      effect on the duration of the freezing/thawing.

PMID- 9168388
TI  - An anisotropic biphasic theory of tissue-equivalent mechanics: the interplay
      among cell traction, fibrillar network deformation, fibril alignment, and cell
      contact guidance.
AB  - We present a general mathematical theory for the mechanical interplay in tissue
      equivalents (cell-populated collagen gels): Cell traction leads to compaction of
      the fibrillar collagen network, which for certain conditions such as a mechanical
      constraint or inhomogeneous cell distribution, can result in inhomogeneous
      compaction and consequently fibril alignment, leading to cell contact guidance,
      which affects the subsequent compaction. The theory accounts for the
      intrinsically biphasic nature of collagen gel, which is comprised of collagen
      network and interstitial solution. The theory also accounts for fibril alignment
      due to inhomogeneous network deformation, that is, anisotropic strain, and for
      cell alignment in response to fibril alignment. Cell alignment results in
      anisotropic migration and traction, as modeled by a cell orientation tensor that
      is a function of a fiber orientation tensor, which is defined by the network
      deformation tensor. Models for a variety of tissue-equivalents are shown to
      predict qualitatively the alignment that arises due to inhomogeneous compaction
      driven by cell traction.

PMID- 9168390
TI  - Temperature distributions during thermoradiotherapy: a sensitivity study with a
      transient numerical model of the rabbit eye.
AB  - An approach to the treatment of medium-sized choroidal melanomas combines
      radiation with ferromagnetic hyperthermia. The study herein discusses results
      with a numerical thermal model of a choroidal melanoma in the rabbit eye as
      treated with episcleral, thermoradiotherapy plaques. The sensitivity of a
      temperature-dependent blood perfusion model is investigated.

PMID- 9168391
TI  - Quantitative characterization of vascular endothelial cell morphology and
      orientation using Fourier transform analysis.
AB  - Fourier Transform methods were used to quantify mean elongation, mean
      orientation, and standard deviation of orientations of cultured vascular
      endothelial cells. Images of cell populations, which had been subjected to 11 and
      20 hours of shear stress at 30 dynes/cm2 and 20 hours of no shear, were analyzed
      by Fourier Transform methods. Measurements of cell morphology and orientation
      characteristics were also obtained using a manual method for comparison purposes.
      The results of the study showed that mean cell orientation can be determined
      accurately with the Fourier Transform methods. Attempts to determine the standard
      deviation of cell orientations, however, resulted in poorer estimates of mean
      elongation and standard deviation of orientations except in the case of exposure
      of endothelial cells to 20 hours of shear, where the actual standard deviation of
      orientations was low. When the value for standard deviation of orientations was
      constrained to zero, a minimum possible mean elongation was determined reliably
      using the Fourier Transform methods. Use of the Fourier Transform methods in
      determining morphological and orientation characteristics of cell monolayers is
      fast and objective and may provide a basis for identifying other characteristics
      of cell shape.

PMID- 9168392
TI  - Mathematical optimization of elastic properties: application to cementless hip
      stem design.
AB  - The designer of a cementless hip stem in total hip replacement must find a
      balance between two conflicting demands. On the one hand, a stiff stem shields
      the surrounding bone from mechanical loading (stress shielding), which may lead
      to bone loss, particularly around the proximal part of the stem. Reducing the
      stem stiffness decreases the amount of stress shielding and hence the amount of
      bone loss. However, this measure inevitably promotes higher proximal interface
      stresses and thereby increases the risk of proximal interface failure. The
      designer's task therefore is to optimize the stem stiffness in order to find the
      best compromise in the conflict. Yet, a better compromise might be found when the
      stem material was nonhomogeneous, in other words when an arbitrary distribution
      of the elastic properties inside the stem was allowed. The number of conceivable
      designs would increase enormously, making the designer's task almost impossible.
      In the present paper, we develop a numerical design optimization method to
      determine the optimal stiffness characteristics for a hip stem. A finite element
      program is coupled with a numerical optimization method, thus producing a design
      optimization scheme. The scheme minimizes the probability for interface failure
      while limiting the amount of bone loss, by adapting the parameters describing the
      nonhomogeneous elastic modulus distribution. As an example, a simplified model of
      a hip stem is made, whose modulus distribution is optimized. Assuming equal long
      term bone loss, the maximum interface stress can be reduced by over 50 percent
      when compared to a homogeneous flexible stem, thus demonstrating the value of the
      new approach.

PMID- 9168393
TI  - Modeling the tensile behavior of the cement-bone interface using nonlinear
      fracture mechanics.
AB  - The tensile mechanical behavior of the cement-bone interface where there was a
      large process (plastic) zone at the interface was modeled using a nonlinear
      fracture mechanics approach. A finite element method was employed, which included
      a piecewise nonlinear interface, to investigate the behavior of experimental
      cement-bone test specimens and an idealized stem-cement-bone (SCB) structure. The
      interface model consisted of a linear elastic region with high stiffness until
      the yield strength was reached, followed by an exponential softening region,
      until zero stress. The yield strength and rate of exponential softening after
      yielding at the cement-bone interface were shown to have a marked effect on the
      structural stiffness of the SCB model. The results indicate that both yield
      strength and postyield behavior should be included to characterize the mechanics
      of the cement-bone interface fully.

PMID- 9168394
TI  - Numerical analysis of an extremity in a cold environment including countercurrent
      arterio-venous heat exchange.
AB  - A model of the thermal behavior of an extremity, e.g., a finger, is presented.
      The model includes the effects of heat conduction, metabolic heat generation,
      heat transport by blood perfusion, heat exchange between the tissue and the large
      blood vessels, and arterio-venous heat exchange. Heat exchange with the
      environment through a layer of thermal insulation, depicting thermal handwear, is
      also considered. The tissue is subdivided into four concentric layers simulating,
      from the center outward, core, muscle, fat, and skin. Differential heat balance
      equations are formulated for the tissue and for the major artery and the major
      vein traversing the finger. These coupled equations are solved numerically by a
      finite-difference, alternating direction method employing a Thomas algorithm. The
      numerical scheme was extensively tested for its stability and convergence. This
      paper presents the model equations and results of the convergence tests, and
      shows plots of blood and tissue temperatures along the axis of the model for
      combinations of parameters including the effect of countercurrent heat exchange
      between the artery and the vein.

PMID- 9168395
TI  - Measurements of velocity and wall shear stress inside a PTFE vascular graft model
      under steady flow conditions.
AB  - The flow field inside a model of a polytetrafluorethylene (PTFE) canine artery
      end-to-side bypass graft was studied under steady flow conditions using laser
      Doppler anemometry. The anatomically realistic in vitro model was constructed to
      incorporate the major geometric features of the in vivo canine anastomosis
      geometry, most notably a larger graft than host artery diameter. The velocity
      measurements at Reynolds number 208, based on the host artery diameter, show the
      flow field to be three dimensional in nature. The wall shear stress distribution,
      computed from the near-wall velocity gradients, reveals a relatively low wall
      shear stress region on the wall opposite to the graft near the stagnation point
      approximately one artery diameter in axial length at the midplane. This low wall
      shear stress region extends to the sidewalls, suture lines, and along the PTFE
      graft where its axial length at the midplane is more than two artery diameters.
      The velocity distribution inside the graft model presented here provides a data
      set well suited for validation of numerical solutions on a model of this type.

PMID- 9168397
TI  - Modeling of flow in a straight stented and nonstented side wall aneurysm model.
AB  - We investigated the changes of flow patterns in a blood vessel with a side wall
      aneurysm resulting from placement of a stent. Local hemodynamics can be markedly
      altered by placing an intravascular stent, which covers the orifice of the
      aneurysm. The alternations in flow patterns can lead to flow stasis in the
      aneurysmal pouch and promote the formation of a stable thrombus. Furthermore, a
      porous stent can serve as substrate for neointimal growth and subsequently induce
      a remodeling of the diseased arterial segment. To examine changes in local
      hemodynamics due to stent placement, a stented and nonstented aneurysm model was
      investigated computationally in a three-dimensional configuration using a finite
      element fluid dynamics program. The finite element model was studied under
      incompressible, pulsatile, viscous, Newtonian conditions. The fluid dynamic
      similarity parameter, i.e., the maximum/minimum Reynolds number, was set at about
      240/25 based on cross-sectional average instantaneous flow. The Womersley number
      was set to 2.5. These values are representative of large cerebral arteries. The
      results of the stented versus the nonstented model show substantial difference
      sin flow patterns inside the aneurysmal pouch. Flow activity inside the stented
      aneurysm model is significantly diminished and flow inside the parent vessel is
      less undulated and is directed past the orifice. A high-pressure zone at the
      distal neck and the dome of the aneurysm prior to stenting decreases after stent
      placement. However, elevated pressure values are found at the stent filaments
      facing the current. Higher shear rates are observed at the distal aneurysmal neck
      after stenting, but are confined to a smaller region and are unidirectional
      compared to the nonstented model.

PMID- 9168396
TI  - The influence of the blunting of the apex on the flow in a vertebro-basilar
      junction model.
AB  - The apex of human vertebro-basilar junctions can be sharp-edged or blunted. In
      the present study, the effect of blunted apex on the flow in vertebro-basilar
      junction models is investigated. We compared the flow phenomena in a series of
      junction models with blunted apices and confluence angles 45, 85, and 125 deg
      with the flow phenomena in a series of junction models with sharp-edged apices
      and the same range of confluence angles, studied in a previous paper
      (Ravensbergen et al., 1996b). The blunting of the apex appears to have an effect
      on the size of the local recirculation area near the apex and the prevailing low
      velocities. Large recirculation areas are found in the models with blunted
      apices, especially in those with small confluence angles. In addition, the
      blunting of the apex has no influence on the flow further downstream, nor on the
      structure and strength of the secondary flow field. Furthermore, a blunted apex
      appears to be a geometric risk factor for atherosclerosis. This supports the
      hypotheses that recirculation areas and low wall shear stress influence the
      development of atherosclerotic plaques.

PMID- 9168398
TI  - Experimental investigation of pulsatile flows in tubes.
AB  - Based on cam-piston-valve arrangement, a mechanical pulsatile flow generator is
      designed to investigate sinusoidal flow and other types of pulsatile flow in
      straight rigid tube. Measurement reveals the relation between pressure gradient
      and flow rate. Numerical simulation using the k-epsilon turbulence model are
      carried out to compare the pulsatile flow produced by the generator with a
      sinusoidal flow and a physiological flow in a rigid tube. The results show that
      the pulsatile flow generated has similar dynamic properties to the physiological
      flow. Hence, the present setup can be used for in-vitro investigation of biofluid
      phenomena.

PMID- 9168399
TI  - Cytokine flow cytometry: understanding cytokine biology at the single-cell level.
AB  - In the past 4 years, cytokine flow cytometry has emerged as the premier technique
      for enumeration of cytokine producing T cells. The multiparameter capability of
      flow cytometry permits the simultaneous detection of two or more cytokines within
      a single cell, allowing true Th1 vs. Th2 determination. The high throughput
      inherent to flow cytometry has enormous advantages when applied to clinical
      research questions previously not amenable for study using labor intensive
      techniques such as ELISPOT, limiting dilution and T cell cloning. Furthermore,
      cytokine flow cytometry allows the study of individual T cells directly ex vivo,
      minimizing artifacts due to long term culture. As such, cytokine flow yields
      unique insights into cytokine biology heretofore not possible. We have used
      cytokine flow cytometry to examine coexpression of cytokines within the
      memory/effector CD4+, CD27- subset. Doing so, we have found distinct cytokine
      producing subsets that correlate with the previously described Th1, Th2 and Th0
      subsets. The majority of cytokine producing cells were of these first two subsets
      with fewer cells coexpressing IFN-gamma and IL-4. These results validate the
      Th1/Th2 hypothesis and demonstrate specific subsets of cytokine producing T cells
      in fresh ex vivo human T cells.

PMID- 9168400
TI  - Human fetal liver cells induce colonies in spleen of lethally irradiated mice.
AB  - Murine hematopoietic tissues contain cells which, upon injection into lethally
      irradiated mice, produce nodules on the surface of their spleen (colony-forming
      unit--spleen; CFU-S). The exact hierarchical level of the hematopoietic
      progenitors which give rise to CFU-S is not fully established; however, cell
      populations highly enriched for repopulating stem cells appear to contain a high
      percentage of CFU-S. The experiments reported here involved the injection of
      human fetal liver cells into mice, under conditions similar to those of the CFU-S
      test. These data demonstrate that human fetal liver cells are able to induce
      spleen colonies (tentatively called human CFU-S) when injected into lethally
      irradiated mice. The number of CFU-S was increased by prior purification of human
      fetal liver cells. When mice were injected with human fetal liver cells
      inactivated by irradiation, no human CFU-S were observed. Positive staining of
      cells found in spleen colonies, using monoclonal antibodies specific for various
      human determinants, indicated the human origin of part of them. The presence of
      human cells within the colonies was further confirmed by in situ hybridization
      using a probe specific for human DNA. A mean of 30-40% of analyzed colonies was
      thus shown to contain some patches of human cells. These data confirm that human
      hematopoietic cells are able to seed, proliferate, and differentiate in a murine
      microenvironment.

PMID- 9168401
TI  - Human anti-Ro autoantibodies bind multiple conformational epitopes of 60-kD Ro
      autoantigen.
AB  - A gel filtration method was developed to estimate the number of conformational
      epitopes on the 60-kD Ro antigen. Anti-Ro Fab or Fab' was incubated with native
      Ro antigen at different ratios and the Stokes radius molecular weight of
      complexes was estimated by gel filtration. Binding was saturated at 9 to 11 Fab
      molecules per bovine Ro molecule. Two additional Fab or Fab' were bound if human
      Ro was used as the antigen. Isolated Ro antigen/anti-Ro Fab complexes were
      evaluated for the relative proportion of antigen to antibody at saturation of
      antigen with antibody and thus stoichiometry was determined. This provided data
      supporting there being between 7 and 11 binding sites, results similar to those
      with the gel filtration method. Experiments carried out with anti-Ro monoclonal
      antibodies showed one binding site per molecule of 60-kD Ro. Therefore, we have
      developed methods to count conformational epitopes on autoantigens and have
      applied it to the Ro/anti-Ro system. The data indicate that multiple
      conformational epitopes can be bound simultaneously by polyclonal anti-Ro sera
      from patients with systemic lupus erythematosus.

PMID- 9168402
TI  - Inverse correlation between IgG-antihinge region and antierythrocyte autoantibody
      in chronic benign and malignant cold agglutination.
AB  - Previous reports provided evidence of an immunosuppressive role of natural anti
      F(ab')2 antibodies. If suppressive anti-F(ab')2 antibodies also regulated the
      autoantibody production in cold agglutination, one would expect high titers of
      anti-F(ab')2 to be associated with low titers of cold agglutinins. Indeed, our
      previous studies revealed an inverse correlation between IgG-anti-F(ab')2 and
      cold agglutinins. Many previous experiments focused on anti-F(ab')2 of an
      antiidiotypic nature. Recent epitope mapping showed that anti-F(ab')2 of healthy
      persons is not an antiidiotype but recognizes a hinge region sequence. We
      attempted to answer the question whether this IgG-antihinge antibody is
      responsible for the previously described association between anti-F(ab')2 and
      cold agglutinins. IgG-antihinge and IgG-anti-F(ab')2 antibody was determined and
      statistically analyzed in the serum of 334 patients with cold agglutination. Our
      experiments revealed a strong correlation between the concentrations of antihinge
      and the previously described anti-F(ab')2 antibody. The anti-F(ab')2 activity was
      competitively inhibited by a synthetic hinge peptide. Moreover, patients with
      high antihinge titers had low cold agglutinin titers, and vice versa. A
      stratification according to cold agglutinin specificity and disease etiology
      showed that the inverse correlation is present only in anti-I and anti-i patients
      suffering from monoclonal B-lymphocyte proliferation. In conclusion, our results
      confirm the correlation previously described for anti-F(ab')2 antibody and
      antierythrocyte autoantibody and define for the first time an association between
      an idiotype-independent anti-IgG autoantibody and cold agglutinin.

PMID- 9168403
TI  - An extract from cultured human keratinocytes that contains the major autoantigens
      related to autoimmune bullous skin diseases.
AB  - Autoantibodies characteristic of autoimmune bullous skin diseases (AIBDs) can be
      detected by immunoblotting on epidermal, dermal, or bovine muzzle extracts.
      However, none of those substrates contain all the autoantigens involved in AIBDs,
      and the diagnosis requires the use of various substrates. Human keratinocytes
      were cultured under such conditions that they expressed the major autoantigens
      associated with AIBDs. Forty-two sera with antiepidermal antibodies were
      immunoblotted on the keratinocyte extract. Bands corresponding to desmoglein III,
      desmoglein I, BPAg2, BPAg1, and type VII collagen were found in 38 sera.
      Desmoplakins I and II were revealed by specific monoclonal antibodies. A review
      of the patients' charts showed a perfect correlation between the blots and the
      diagnoses of pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid,
      cicatricial pemphigoid, and epidermolysis bullosa acquisita. Four sera revealing
      no band typical of AIBD were from patients with no autoimmune skin disease.
      Therefore, a single extract of keratinocytes can be used for the differential
      diagnosis of AIBDs.

PMID- 9168405
TI  - Different regulatory effects of pentoxifylline on human T cell activation
      pathways.
AB  - Pentoxifylline (PTX), a methylxanthine derivative, was examined for its effects
      on T cell proliferation and cytokine production stimulated by cross-linking anti
      CD3 alone, anti-CD3 with PMA, anti-CD3 with anti-CD26, or anti-CD3 with anti-CD28
      mAb, respectively. PTX at a 3.5 x 10(-5) M concentration significantly inhibited
      T cell proliferation and the production of tumor necrosis factor-alpha,
      interleukin-2, and interleukin-4. Moreover, this effect was selective for
      stimulation by cross-linking anti-CD3 with PMA, or anti-CD3 with anti-CD26, but
      not by cross-linking anti-CD3 with anti-CD28. These results suggest that the
      inhibitory effect of PTX on T cell activation involves the CD3 and CD26, but not
      the CD28 signal pathway.

PMID- 9168407
TI  - The Chiropractic Outcome Study: pain, functional ability and satisfaction with
      care.
AB  - OBJECTIVE: To examine changes in pain experienced, changes in functional ability
      and degree of patient satisfaction with chiropractic care. Patient
      characteristics influencing these parameters were also explored. DESIGN: A follow
      up study consisting of a questionnaire to be completed at the beginning of
      treatment and a mailed questionnaire 6 wk later. SETTING: Non-random sample of 13
      chiropractic practices in Calgary and Red Deer, Alberta, Canada. PATIENTS: Three
      hundred sixty-nine patients presenting with neck and/or back pain who saw a
      chiropractor for the first time or who had not seen a chiropractor for a period
      for 6 months before the first visit. RESULTS: Pain relief and changes in
      functional ability were greatest among patients whose initial pain or disability
      level was moderate or severe. No significant improvement was found among those
      whose initial level of pain or disability was mild. Pain relief and improved
      functional ability was greatest among those with an acute condition and those who
      saw no one other than the chiropractor during treatment. In addition, pain relief
      was highest among men, those who perceived themselves to be in good or excellent
      health and those who had completed treatment in 6 wk. Patients positively
      endorsed all items on the satisfaction questionnaire, indicating a high level of
      satisfaction with the care they received. Patients were most satisfied with
      access to chiropractic care and least satisfied with financial aspects.
      Improvement in pain and in back and neck disability were significantly related to
      general satisfaction. CONCLUSION: Based on these results, it seems that patients
      suffering from back and/or neck complaints experience chiropractic care as an
      effective means of resolving or ameliorating pain and functional impairments,
      thus reinforcing previous results showing the benefits of chiropractic treatment
      for back and neck pain.

PMID- 9168404
TI  - Impaired induction of the apoptosis-protective protein Bcl-xL in activated PBMC
      from asymptomatic HIV-infected individuals.
AB  - Progression to AIDS in asymptomatic HIV-infected individuals is characterized by
      a gradual but progressive loss of CD4+ T cells. While the mechanisms underlying
      this decline are currently unknown, recent evidence suggests that these cells are
      abnormally sensitive to apoptosis in response to activation signals. Recent work
      has implicated downregulation of Bcl-2 with the increased spontaneous apoptosis
      in lymphocytes from HIV-infected patients. We have evaluated the roles of the
      apoptosis-protective proteins Bcl-2 and Bcl-x in stimulated PBMC from
      asymptomatic HIV-infected and HIV-uninfected individuals. We found that Bcl-2 was
      constitutively expressed in PBMC from both HIV-infected and uninfected samples.
      However, Bcl-x induction was delayed and responses were decreased in stimulated
      HIV-infected samples. Additionally, single-cell intracellular staining of Bcl-x
      revealed a significant inverse correlation between PWM-induced Bcl-x expression
      and apoptosis (r = -0.695, P = 0.05). This was confirmed at the single-cell level
      in direct experiments when stimulated cells were sorted based on Bcl-x induction
      and then measured for apoptosis. Furthermore, low Bcl-x expression was not due to
      reduced lymphocyte activation following PWM stimulation. Our data indicate that
      the induction of Bcl-x is markedly impaired in asymptomatic HIV-infected patients
      and that stimuli which induce inadequate expression of Bcl-x are associated with
      increased levels of apoptosis in these cells.

PMID- 9168406
TI  - Interleukin-1 beta, interleukin-1 receptor antagonist, and soluble interleukin-1
      receptor type II secretion in chronic fatigue syndrome.
AB  - Chronic fatigue syndrome is a condition that affects women in disproportionate
      numbers, and that is often exacerbated in the premenstrual period and following
      physical exertion. The signs and symptoms, which include fatigue, myalgia, and
      low-grade fever, are similar to those experienced by patients infused with
      cytokines such as interleukin-1. The present study was carried out to test the
      hypotheses that (1) cellular secretion of interleukin-1 beta (IL-1 beta),
      interleukin-1 receptor antagonist (IL-1Ra), and soluble interleukin-1 receptor
      type II (IL-1sRII) is abnormal in female CFS patients compared to age- and
      activity-matched controls; (2) that these abnormalities may be evident only at
      certain times in the menstrual cycle; and (3) that physical exertion (stepping up
      and down on a platform for 15 min) may accentuate differences between these
      groups. Isolated peripheral blood mononuclear cells from healthy women, but not
      CFS patients, exhibited significant menstrual cycle-related differences in IL-1
      beta secretion that were related to estradiol and progesterone levels (R2 = 0.65,
      P < 0.01). IL-1Ra secretion for CFS patients was twofold higher than controls
      during the follicular phase (P = 0.023), but luteal-phase levels were similar
      between groups. In both phases of the menstrual cycle, IL-1sRII release was
      significantly higher for CFS patients compared to controls (P = 0.002). The only
      changes that might be attributable to exertion occurred in the control subjects
      during the follicular phase, who exhibited an increase in IL-1 beta secretion 48
      hr after the stress (P = 0.020). These results suggest that an abnormality exists
      in IL-1 beta secretion in CFS patients that may be related to altered sensitivity
      to estradiol and progesterone. Furthermore, the increased release of IL-1Ra and
      sIL-1RII by cells from CFS patients is consistent with the hypothesis that CFS is
      associated with chronic, low-level activation of the immune system.

PMID- 9168408
TI  - Interprofessional contacts between chiropractors and other health-care
      professionals in Sweden as seen from a chiropractic perspective.
AB  - OBJECTIVE: To investigate the type and extent of interprofessional contacts
      between chiropractors and members of the conventional Swedish health-care system
      and to study the possible barriers to effective cooperation between these groups.
      DESIGN: Surveys through self-administered questionnaires and a structured
      telephone interview. PARTICIPANTS: Twenty consecutive patients of 31
      chiropractors (n = 616) participated in the questionnaire survey, and 15 randomly
      selected chiropractors participated in the telephone interview. SETTING:
      Chiropractic practices in Stockholm, Sweden. MAIN OUTCOME MEASURES: Information
      was sought on the type and number of interprofessional contacts and on barriers
      to free and effective communication. RESULTS: Eighteen percent of patients were
      recommended to chiropractic care by some other health-care practitioner. Only 1%
      of the participating patients were referred for chiropractic care with a written
      request. Almost all chiropractors (87%) could provide a list of the last three
      health-care professionals with whom they had contact. The median number of
      interprofessional contacts per month was estimated by the chiropractors to be 10.
      Legal recognition of chiropractors and the inclusion of these in the County
      Council reimbursement program were thought to have improved the image of
      chiropractic. Considerable barriers to cooperation were stated to exist still.
      CONCLUSION: Successful integration of chiropractors into the Swedish health-care
      system requires an overall policy plan and practical guidelines of cooperation.

PMID- 9168409
TI  - Evaluation of the assumptions used to derive an ideal normal cervical spine
      model.
AB  - OBJECTIVES: To evaluate the accuracy of anatomical assumptions made to derive a
      geometrical, ideal, normal model of the upright, static, sagittal cervical spine,
      to make comparisons with other spinal models and to discuss the implications of a
      normal cervical model. BACKGROUND: Anatomical assumptions were made based on
      observations to assist in the development of a computerized geometrical model of
      the ideal upright, static, sagittal cervical spine. These assumptions address the
      magnitudes of the contribution made by the vertebral bodies and intervertebral
      discs to the overall magnitude and geometric shape of the cervical lordosis.
      STUDY DESIGN: (a) Data were collected from 400 lordotic lateral cervical
      radiographs and compared with the predictions of a geometric normal cervical
      lordotic model. Angels of intersecting tangent lines, drawn at posterior
      vertebral body margins, were measured at each disc space and between C2 and C7.
      Height-to-length ratios and an anterior weight-bearing distance were measured.
      (b) LITERATURE REVIEWs were obtained through Medline and Chirolars. RESULTS: (a)
      Modeling: the 400 sample subjects varied from the geometric model by
      approximately 5%. Subgroup averages, from partitioning the C2-C7 angle into 5
      degrees intervals, were less than 8% in error to model predictions. (b)
      LITERATURE REVIEW: lordosis is the normal configuration for the cervical spine
      and many chiropractic empirical models are similar. CONCLUSIONS: The anatomical
      assumptions used to derive our normal geometric model of the cervical lordosis
      seem to be supported by the average values and literature reviewed. Two typical
      geometric configurations of the cervical spine were identified as a normal
      circular lordotic arc of 34 degrees and an ideal normal of 42 degrees. LITERATURE
      REVIEWed establishes cervical lordosis as a desirable clinical outcome of care.

PMID- 9168410
TI  - Physical examination of the cervical spine and shoulder girdle in patients with
      shoulder complaints.
AB  - OBJECTIVE: To look for differences in mobility in randomly selected patients
      without shoulder complaints depending on age, gender and left- or right
      handedness; to investigate in the patient group whether specific differences
      exist, depending on the diagnosis made or the afflicted side; and to detect
      differences between the findings on the mobility examination of the cervical and
      cervicothoracic spine in patients with shoulder complaints compared with the
      healthy population. DESIGN: Comparative study. METHOD: The physical examination
      findings after inclusion and after 26 wk of 101 shoulder patients were compared
      with those of 75 randomly selected patients without shoulder complaints and
      adjusted for age and gender. RESULTS: In the population of patients without
      shoulder complaints, the mobility in the cervical and upper thoracic spine was
      found to decrease with aging. Significant differences were found between the
      healthy and the afflicted population at the time of inclusion as well as after 26
      wk, even though the majority of patients felt cured at that time. With all types
      of shoulder complaints, functional disorders in the shoulder girdle were found in
      which, at the time of inclusion, the emphasis was on pain and, after 26 wk, on
      restricted motion. Thus, functional disorders in the cervical spine, the higher
      thoracic spine and the adjoining ribs are not extrinsic causes of shoulder
      complaints, but an integral part of the intrinsic causes of shoulder complaints.
      CONCLUSION: Further study is needed to determine if this finding explains the
      high recurrence rate of shoulder complaints. It may be advisable to include the
      treatment of functional disorders of the shoulder girdle in treatment of patients
      with shoulder complaints.

PMID- 9168411
TI  - The use of epidural steroid injection and manipulation on patients with chronic
      low back pain.
AB  - OBJECTIVES: To document the efficacy of combined epidural steroid injection (ESI)
      and manipulation to the lumbar spine in patients suffering from chronic low back
      pain (LBP). SUMMARY OF BACKGROUND DATA: The use of ESI in conjunction with lumbar
      manipulation has seldom been reported in the literature but has offered promising
      results when studied. STUDY DESIGN: Retrospective repeated-measures analysis of
      patients with chronic LBP who received ESIs combined with spinal manipulation.
      METHODS: A retrospective analysis using a repeated-measures format was performed
      on 17 cases of patients who had received ESI and manipulation to the lumbar
      spine. All patients were medically stable for chronic mechanical LBP and had
      experienced a suboptimal response to conventional care. The principle
      investigator was blinded from data outcomes when determining patient eligibility
      for the study. A subjective patient improvement scale was used to monitor degree
      of success. RESULTS: Ten of the 17 patients were eligible for the study. Patients
      were eliminated for lack of consistency of data collection, having received an
      additional procedure after conventional care, involvement of the cervical spine;
      one patient experienced an unrelated medical problem. After 1 yr of conventional
      care, the patients reported a 25.5% improvement. (Conventional care included ESI
      and manipulation done at separate times.) After on ESI with subsequent
      manipulation, these same patients reported a 50.5% improvement. Mean improvement
      was 25.00% (SD = 19.51, SEM 6.19, t = 4.04 and p = .0015). CONCLUSION: The use of
      ESI performed with manipulation seems to offer promise for a carefully selected
      group of patients. ESI combined with manipulation should be considered in
      patients who do not respond to conventional forms of care.

PMID- 9168412
TI  - A review of diagnostic ultrasound of the spine and soft tissue.
AB  - BACKGROUND: Current medical applications for diagnostic ultrasound are numerous.
      The technology is attractive because of its ease of use, noninvasive nature and
      low cost. Recent technological advances have improved ultrasound images of spine
      related soft tissues. OBJECTIVE: To examine and summarize the spine-related
      diagnostic ultrasound literature to help aid in understanding its possible
      applications. DATA SOURCES: This literature search was part of a larger search in
      which several hundred musculoskeletal diagnostic ultrasound articles were
      collected. MEDLINE from 1970 to present was searched electronically. Chiropractic
      Research Archives Collection (Vol. I-IV) were inspected manually. Bibliographies
      and references from studies obtained were examined thoroughly for additional
      references. DATA SYNTHESIS: All articles related to diagnostic ultrasound and its
      spinal applications were collected and reviewed, except those focusing on
      intraoperative spinal ultrasound in neurosurgery. RESULTS: Ultrasound has long
      been used to measure the spinal canal, detect cord abnormalities and examine soft
      tissue abnormalities. Recently, it has been used to quantify scoliotic curves,
      measure multifidus muscle size and image sciatic nerve lesions. CONCLUSION:
      Several well-documented applications of spine-related diagnostic ultrasound,
      along with many new possible applications, make this technology important to any
      clinician interested in noninvasive diagnostic applications for the spine and
      soft tissue.

PMID- 9168413
TI  - Symptoms of neck artery compromise: case presentations of risk estimate for
      treatment.
AB  - OBJECTIVE: To discuss the use of magnetic resonance angiography (MRA) imaging as
      a definitive means to assess vascular patency and the relative value of various
      vertebral artery screening maneuvers. CLINICAL FEATURES: Two female patients
      suffered head and neck trauma with possible vertebral artery insufficiency.
      Positive vertebral artery screening tests with consistent symptoms were present
      in both cases. One patient had a congenitally narrowed vertebral artery, whereas
      the second had no evidence of vascular anomaly. INTERVENTION AND OUTCOME:
      Conservative chiropractic management using manipulation and rehabilitation led to
      favorable outcome in both cases. The patient with vascular compromise received a
      treatment plan avoiding neck manipulation. The second case received manipulation
      per clinical indications from neck findings. CONCLUSION: MRA imaging may be more
      important to critical decision making than are the various vertebral artery
      screening tests in patients with positional vertigo on combined neck extension
      and rotation.

PMID- 9168414
TI  - Proprioceptor: an obsolete, inaccurate word.

PMID- 9168416
TI  - A normal sagittal spinal configuration: a desirable clinical outcome.

PMID- 9168415
TI  - Searching chiropractic literature: a comparison of three computerized databases.

PMID- 9168417
TI  - Strabismus surgery: simply cosmetic?

PMID- 9168418
TI  - Spectrum of pediatric dacryocystitis: medical and surgical management of 54
      cases.
AB  - BACKGROUND: Dacryocystitis in infants and older children is a serious
      complication of congenital or acquired nasolacrimal duct obstruction. To define
      the modes of presentation and treatment strategies of this disorder better, we
      reviewed the clinical courses of 54 children treated for dacryocystitis at St
      Louis Children's Hospital. METHODS: Clinical, neuroradiologic, and laboratory
      data were collated for all cases of dacryocystitis treated from 1990 to 1995.
      Average follow up of the children in this consecutive series was 1.75 years
      (range, 4 months to 5 years). RESULTS: Of the 54 patients, 36 (67%) had chronic
      low-grade dacryocystitis, which was treated with nasolacrimal duct probing on an
      outpatient basis. The remaining 18 patients (33%) had acute dacryocystitis, which
      was treated with a combined medical/surgical strategy. Medical treatment
      consisted of hospital admission for administration of intravenous antibiotics
      followed by inpatient surgery, which varied according to the age of the patient
      and the clinical history: 1) Acute dacryocystitis in neonates was treated
      surgically by nasolacrimal duct probing and nasal endoscopy for excision of
      intranasal duct cyst; 2) Acute dacryocystitis with periorbital cellulitis was
      treated surgically by nasolacrimal duct probing; 3) Acute dacryocystitis due to
      facial trauma was treated surgically by dacryocystorhinostomy and stent
      placement; and 4) Acute dacryocystitis complicated by orbital abscess was treated
      by inferior orbitotomy for orbital abscess drainage, simultaneous nasolacrimal
      duct probing, and stent placement. CONCLUSION: Dacryocystitis in the pediatric
      population may present in either chronic or acute forms. An effective and safe
      treatment for acute dacryocystitis is hospital admission, both for administering
      intravenous antibiotics and monitoring to rule out orbital cellulitis or abscess
      formation. Intravenous antibiotic therapy is followed within a day or two by
      surgery tailored to the clinical history. In the majority of both chronic and
      acute cases, nasolacrimal duct probing appears to be an effective treatment
      strategy.

PMID- 9168419
TI  - Costenbader Lecture. A and V syndrome: a historical perspective.

PMID- 9168420
TI  - Psychosocial implications of strabismus surgery in adults.
AB  - PURPOSE: Adults with socially noticeable strabismus have been known to experience
      psychosocial difficulties as a result of their abnormal eye position. This study
      was designed to assess the impact of noticeable strabismus in adults and the
      psychosocial effects of surgical correction. METHODS: A total of 31 adults who
      underwent surgery for longstanding horizontal strabismus where poor alignment was
      the primary reason for consenting to surgery were requested to complete a self
      reporting repertory grid to appraise the psychosocial consequences of corrective
      strabismus surgery. RESULTS: Prior to corrective surgery, the majority of
      subjects reported various psychosocial difficulties, considered by them to be
      wholly or partly due to their unsightly strabismus. A significant improvement in
      interpersonal interactions is apparent following strabismus surgery. CONCLUSION:
      Surgery to improve ocular alignment appears to herald major improvements in the
      quality of psychosocial functioning for the majority of adults undergoing such
      surgical procedures (P < 0.001).

PMID- 9168422
TI  - Myopia predicts better outcome in persistent hyperplastic primary vitreous.
AB  - PURPOSE: Persistent hyperplastic primary vitreous (PHPV) is a congenital disorder
      that presents with a spectrum of ocular anomalies, including cataracts,
      microphthalmia, and hyaloid vessel remnants. Severe visual loss due to secondary
      glaucoma and retinal detachment is common. This report evaluates the visual
      outcome of a variant of PHPV with myopia not associated with glaucoma. METHODS:
      The records of 23 consecutive patients with the diagnosis of PHPV (all
      unilateral) from October 1992 to August 1995 were reviewed. All but three
      patients had a cataract extraction procedure and all underwent amblyopia therapy.
      Eyes with a phakic myopic refractive error (Rx) or aphakic refractive correction
      < or = 8.5 diopters (D) in the immediate postoperative period were designated as
      myopic. RESULTS: Six patients were in the myopic group (Group 1) and 17 in were
      the nonmyopic group (Group 2). The mean age of diagnosis was 21.1 months in Group
      1 versus 2.0 months in Group 2, with a comparable follow-up period of 36 months.
      The mean preoperative Rx of Group 1 was -7.78 D. The mean aphakic Rx of Group 2
      was +18.29 D. Average axial length measurement determined by echography was 22.46
      mm in Group 1 and 14.03 mm in Group 2. The mean corneal diameter was 11.3 mm in
      Group 1 vs 8.9 mm in Group 2. In Group 2, seven eyes developed retinal detachment
      and four developed glaucoma. These complications did not develop in Group 1
      during the follow-up period. Overall functional visual acuity was better in Group
      1, with a median visual acuity at final follow up of 20/160, as compared with
      light perception for Group 2. CONCLUSIONS: PHPV eyes with myopia were not
      detected as early as the typical PHPV eyes, primarily because of less media
      opacification and near-normal corneal diameters. These eyes showed a more
      favorable visual outcome as they were less likely to develop typical PHPV-related
      postoperative complications. Myopic PHPV eyes may require a different management
      approach.

PMID- 9168421
TI  - The effect of chemoreduction on retinoblastoma-induced retinal detachment.
AB  - BACKGROUND: Retinoblastoma with total retinal detachment traditionally has been
      managed with enucleation. We employed a chemoreduction protocol in an effort to
      reduce the tumor size to allow for focal treatment and salvage of the eye.
      METHODS: A prospective study was performed to assess the effects of a 2-month
      chemoreduction regimen of vincristine, etoposide, and carboplatin on massive
      retinoblastoma with total retinal detachment. RESULTS: We treated 17 eyes with
      total retinal detachment from retinoblastoma in 13 patients over a 14-month
      period. At the initial examination, the mean tumor base was 15 mm and mean
      thickness was 10 mm. The eyes were classified as Reese-Ellsworth group V in 16
      cases (94%) and group III in one case (6%). The retina was totally detached with
      serous subretinal fluid in all cases. After 2 months of chemoreduction, all
      tumors showed a response, and the tumors decreased to a mean base of 10 mm and
      thickness of 5 mm. Overall, a mean of 33% decrease in base and 47% decrease in
      thickness was noted. The subretinal fluid had resolved completely in seven eyes
      (41%), leaving flat retina. In three eyes (18%), partial resolution was achieved;
      in seven eyes (41%), minimal resolution of the subretinal fluid at the 2-month
      period was noted. By last follow up, at a mean of 10 months after initiation of
      chemoreduction, complete resolution of the subretinal fluid occurred in 13 eyes
      (76%) and partial resolution of subretinal fluid occurred in four eyes (24%).
      CONCLUSION: Preliminary observations suggest that chemoreduction may be an
      important tool in the initial management of retinoblastoma, even for large tumors
      with total retinal detachment. Tumor shrinkage may be dramatic and subretinal
      fluid resolution may be complete.

PMID- 9168423
TI  - Predictive value of temporal retinal disease in retinopathy of prematurity.
AB  - PURPOSE: Screening examinations for retinopathy of prematurity (ROP) can be
      stressful to the premature infant. The temporal retina is the most easily
      visualized area of the peripheral retina. This study was undertaken to determine
      whether evaluation of the temporal peripheral retina provides a reliable
      indicator of the ROP status of the entire retina. METHODS: A total of 690 ROP eye
      examinations were performed on 156 premature infants. Eye examinations of 95
      patients were reviewed retrospectively and of 61 patients prospectively. All
      patients were born at less than 34 weeks estimated gestational age (EGA) and had
      a birth weight less than 1600 g. No examinations were performed prior to 4 weeks
      of age. Each eye examination was considered independently. The fundus examination
      was recorded using the International Classification of Retinopathy of
      Prematurity. The temporal four clock hours of retina were classified as the
      "temporal" retina. The remainder of the peripheral retina was classified as
      "nontemporal." RESULTS: A highly significant correlation (Pearson correlation
      coefficient = 0.88) between the severity (ie, stage) of temporal ROP and the
      severity of nontemporal ROP was noted. The status of temporal ROP was found to be
      more advanced or the same as nontemporal retina in 91.2% of the examinations.
      Nontemporal disease was found to be more severe than temporal disease in 8.8% of
      the examinations, but only 0.4% of examinations indicated nontemporal disease
      that was worse than temporal disease by more than one stage. CONCLUSIONS: The
      temporal retinal disease status in ROP is strongly predictive of the disease
      status of the entire retina. An abbreviated retinal examination of the temporal
      clock hours provides a reliable indicator of the highest stage of ROP present in
      the entire retina. Such a screening examination, although not recommended for
      routine screening, may be useful when a complete ROP examination cannot be
      performed because of physiologic instability or poor visibility.

PMID- 9168424
TI  - Retinal examinations in infants after extracorporeal membrane oxygenation.
AB  - BACKGROUND: Ophthalmic examinations performed in infants undergoing
      extracorporeal membrane oxygenation (ECMO) are recommended because ocular
      abnormalities have been known to occur after this procedure. METHODS: We reviewed
      medical records of infants treated with ECMO was subsequently underwent routine
      ophthalmic examination prior to or immediately after hospital discharge.
      Examinations were performed in a fashion similar to that for retinopathy of
      prematurity screening. RESULTS: Eye examinations were recorded for 171 patients
      (342 eyes). Fundus examination was normal in 302 eyes (88%). Abnormal
      retinovascular findings such as venous dilation or intraretinal hemorrhages, when
      present, were not considered vision threatening and required no treatment.
      CONCLUSION: Clinically important retinal findings were not identified in our
      patients undergoing postECMO screening. Routine dilated fundus examination is
      probably not cost effective and places additional and potentially unnecessary
      stress on these infants.

PMID- 9168425
TI  - Recording sensory and motor aspects of strabismus.

PMID- 9168426
TI  - Large congenital upper lid coloboma--successful delayed conservative management.

PMID- 9168427
TI  - Congenital absence of the superior oblique tendon in a patient with
      neurofibromatosis.

PMID- 9168428
TI  - Congenital orbital lipoblastoma: a pathologic and radiologic study.

PMID- 9168429
TI  - Ophthalmia nodosa caused by tarantula hairs.

PMID- 9168430
TI  - Molecular analysis of infant acute leukemia.
AB  - Infant acute leukemia, known to have a poor outcome with conventional therapy,
      usually has a molecular rearrangement at chromosome band 11q23. The 11q23
      translocation partner is typically at 4q21 in infant ALL, but other 11q23
      translocation partners occur in infant ALL and AML. The MLL gene at 11q23, and
      the AF4 gene at 4q21, have been extensively studied to identify heterogeneity of
      structural rearrangement and prognostic indicators, to look for clues as to
      etiology, and to improve therapy.

PMID- 9168431
TI  - C-kit receptors in childhood malignant lymphoblastic cells.
AB  - The product of the protooncogene c-kit is the receptor for the hematopoietic
      cytokine stem cell factor (SCF). C-kit is expressed on leukemic cells of the
      erythroid, myeloid, and mast-cell lineage and SCF has a proliferative effect on
      some of these cells. The role of SCF and c-kit in lymphoid malignancies is much
      less clear. Here we review the role of c-kit in normal lymphopoiesis and
      summarize its role in lymphoid malignancies. C-kit is expressed in normal
      lymphopoiesis and its ligand SCF synergizes with IL-7 to enhance the
      proliferation of B- and T-cell progenitors. In malignant lymphopoiesis, c-kit can
      also be expressed in B and T-lymphoblastic cells from children with non Hodgkin's
      lymphoma (NHL) or acute lymphoblastic leukemia (ALL) when analyzed by the highly
      sensitive reverse transcriptase polymerase chain reaction (RT-PCR). While c-kit
      receptors were detected by flow cytometric (FCM) analysis on about 40% of fresh T
      lymphoblastic biopsy tumor cell preparations or T-lymphoblastic cell lines, no
      receptors were detected on B-lymphoblastic fresh cells or cell lines from
      children with B-ALL or Burkitt's lymphoma (BL). Almost all of the lymphoblastic
      cells expressing c-kit protein responded to recombinant human (rh)SCF with a
      downregulation of c-kit receptors. A proliferative response was detected only in
      a minority of these cells. B-ALL or BL cell lines showed no response to rhSCF.
      Upregulation of c-kit in T-lymphoblastic cells could be demonstrated by the
      addition of IL-1 beta, TNF-alpha, TGF-beta or A23187, and downregulation by rhSCF
      or phorbol myristate acetate (PMA). Despite upregulation of c-kit mRNA, protein
      remained undetectable on B-ALL or BL cells in the presence of A23187. The
      metabolic state of the cells seemed to influence c-kit expression, since c-kit
      was upregulated in T-lymphoblastic cells by the addition of new medium. C-kit
      appears to play a role in the growth of some malignant T-lymphoblastic but not B
      lymphoblastic cells.

PMID- 9168432
TI  - Inflammatory reactions induced by pretransplant conditioning--an alternative
      target for modulation of acute GvHD and complications following allogeneic bone
      marrow transplantation?
AB  - Intensity of pretransplant conditioning has been closely correlated with regimen
      related toxicity in patients receiving allogeneic bone marrow transplantation
      (BMT). In this review, we summarize evidence for a direct link between
      inflammatory reactions induced by irradiation and cytotoxic treatment and
      occurrence of acute graft-versus-host disease (GvHD) as well as endothelial
      complications: In our studies, de novo release of TNFalpha during conditioning
      was associated with an increased risk of severe GvHD and mortality following BMT,
      whereas increased spontaneous production of IL-10, an endogenous TNF-antagonist,
      prior to conditioning protected from these complications. Immunogenetic
      differences in cytokine regulation and costimulation by endotoxin proved to be
      important cofactors determining the extent of inflammatory cytokine release in
      individual patients. Pathophysiological relevance of these findings seems to be
      confirmed by experimental as well as first clinical trials using TNF-antibodies
      and related antagonists during pretransplant conditioning. Preclinical
      experiments suggest additional, cytokine independent inflammatory reactions
      induced by irradiation such as expression of ICAM-1 and endothelial cell
      apoptosis. Although the exact impact of these findings on pathophysiology of BMT
      related complications needs further clarification by future studies, conditioning
      related inflammation as a first crucial step in induction of GvHD and
      complications has to be considered when designing new protocols for preparation
      of patients for allogeneic BMT.

PMID- 9168433
TI  - Clinical and biological aspects of Philadelphia-negative/BCR-negative chronic
      myeloid leukemia.
AB  - The Philadelphia (Ph) chromosome was the first chromosomal abnormality associated
      with a specific leukemia, chronic myeloid leukemia (CML). This chromosome arises
      from the t(9;22)(q34;q11) translocation which results in the juxtaposition of the
      bcr gene and the abl proto-oncogene. This BCR/ABL fusion gene encodes for a
      hybrid protein with the capacity of oncogenic transformation of hematopoietic
      cells. Nonetheless, very few myeloproliferative disorders (about 10%) included
      under the generic term of CML have no Ph chromosome. Half of these Ph-negative
      CML have the BCR/ABL fusion gene (BCR-positive) and are considered equivalent to
      Ph-positive CML. In contrast, the patients without detectable BCR/ABL fusion (BCR
      negative) fulfil the criteria for atypical CML (aCML) of the French-American
      British (FAB) classification, despite considerable variability at the individual
      level. Due to the very small number of patients with precise cytological
      descriptions already published, cooperative studies focused on aCML are warranted
      to draw definitive conclusions and to provide some pointers on physiopathology.

PMID- 9168434
TI  - Venocclusive disease of the liver after bone marrow transplantation: the role of
      hemostasis.
AB  - Venocclusive disease of the liver is a relatively frequent early complication of
      bone marrow transplantation related to pre-transplant toxic injury to the liver.
      Events that lead to toxicity of the liver in the pre-transplant setting are
      infection, anti-neoplastic and anti-infectious drug administration and radiation.
      The histological correlates of venocclusive disease are lesions mainly localized
      to structures in zone 3 of the liver acinus and in the sublobular central
      venules. At some point in the pathogenesis of venocclusive disease, blood
      clotting and inflammation occur. The first is characterized by laboratory signs
      of coagulation activation, by an increase in several procoagulant proteins and by
      a decrease in naturally occurring anticoagulants, particularly protein C, the
      latter being a sensitive index of liver injury. Inflammation is mediated by
      cytokine production, which maintains procoagulant endothelial responses and liver
      injury. Severe venocclusive disease is associated with multi-organ failure and
      elevated mortality. Attempts at finding predictive markers of the disease have
      succeeded in identifying some coagulation and inflammatory proteins which can be
      useful in predicting the occurrence of VOD in selected patient groups. The role
      of hemostasis in venocclusive disease is underscored also by the reports on the
      successful prophylaxis and management of the disease with heparin and
      thrombolytic agents.

PMID- 9168435
TI  - Granulocyte-macrophage colony-stimulating factor receptor-targeted therapy of
      chemotherapy- and radiation-resistant human myeloid leukemias.
AB  - Contemporary therapies for acute myeloid leukemia (AML) commonly fail to cure
      patients because of the emergence of drug resistance. Drug resistance in AML is
      multifactorial but can be associated with the overexpression of transmembrane
      transporter molecules, including P-glycoprotein (Pgp) or the multidrug resistance
      associated protein (MRP), or associated with inactivation of the p53 tumor
      suppressor gene, as well as overexpression of the anti-apoptotic protein bcl-2.
      We are investigating if novel recombinant biotherapeutics can circumvent these
      resistance mechanisms to effectively treat refractory AML. To target the lethal
      action of diphtheria toxin (DT) to high affinity granulocyte-macrophage colony
      stimulating factor (GMCSF) receptors on AML blasts, we have produced a
      recombinant chimeric fusion toxin, DTctGMCSF. Since DTctGMCSF enters and kills
      its target cells by unique mechanisms (GMCSF-receptor binding and protein
      synthesis inhibition) and is not similar in structure to Pgp or MRP substrates,
      we postulated that it would be an active agent against therapy-resistant AML.
      DTctGMCSF was selectively cytotoxic (IC50 1-10ng/ml) to GMCSF-receptor positive
      AML cells expressing the Pgp- or MRP-associated multi-drug resistant phenotypes,
      despite high level resistance to conventional chemotherapeutic agents. DTctGMCSF
      also efficiently killed AML cells deficient in p53 expression, as well as
      radiation-resistant AML cells and mixed lineage leukemia cells expressing high
      levels of bcl-2. In addition, DTctGMCSF killed > 99% of primary leukemic
      progenitor cells from therapy-refractory AML patients under conditions that we
      have previously found to not adversely affect the proliferative capacity or
      differentiation of pluripotent normal hematopoietic progenitor cells. DTctGMCSF
      may prove useful in treating myeloid leukemias that are otherwise resistant to a
      wide range of conventional therapies.

PMID- 9168436
TI  - A recombinant fusion toxin targeted to the granulocyte-macrophage colony
      stimulating factor receptor.
AB  - Human granulocyte-macrophage colony stimulating factor (GMCSF) and its high
      affinity receptor function to regulate the proliferation and differentiation of
      myeloid lineage hematopoietic cells, and may participate in the pathogenesis of
      many malignant myeloid diseases. We have used genetic engineering based on the
      elucidated molecular structures of human granulocyte-macrophage colony
      stimulating factor and diphtheria toxin (DT) to produce a recombinant fusion
      toxin, DTctGMCSF, that targets diphtheria toxin to high affinity GMCSF receptors
      expressed on the surface of blast cells from a large fraction of patients with
      acute myeloid leukemia (AML). DTctGMCSF was specifically immunoreactive with
      antidiphtheria toxin and anti-GMCSF antiseras, and exhibited the characteristic
      catalytic activity of diphtheria toxin, catalyzing the in vitro ADP-ribosylation
      of purified elongation factor 2. The cytotoxic effects of DTctGMCSF were examined
      using the 3-(4,5-dimethylthiazol-2-yl)-2,5-tetrazolium (MTT) bromide assay of
      cell viability and in vivo assays of protein synthesis inhibition. DTctGMCSF were
      specifically cytotoxic to human leukemia cell lines bearing high affinity
      receptors for human GMCSF with IC50 of 10(-9) to 10(-11) M. It was not toxic to
      mammalian hematopoietic cell lines lacking human GMCSF (hGMCSF) receptors. In
      receptor positive cells, cytotoxicity can be specifically blocked by a large
      excess of hGMCSF, confirming that its cytotoxicity is mediated through the hGMCSF
      receptor. THough DTctGMCSF inhibited granulocyte-macrophage colony formation by
      committed myeloid progenitor cells (CFU-GM), it did not significantly affect
      erythroid burst formation by committed erythroid progenitor cells (BFU-E), or
      mixed granulocyte-erythroid-macrophage-megakaryocyte colony formation by
      pluripotent multilineage progenitor cells (CFU-GEMM). DTctGMCSF holds promise for
      the treatment of myeloid lineage malignancies, and is a useful reagent to study
      hematopoiesis.

PMID- 9168437
TI  - N-(4-hydroxyphenyl)retinamide induces apoptosis in T lymphoma and T
      lymphoblastoid leukemia cells.
AB  - We demonstrate that N-(4-hydroxyphenyl)-all-trans-retinamide (4-HPR), a synthetic
      retinoic acid (RA) derivative, is a potent and selective inducer of apoptosis in
      malignant T lymphoid cells, but has little effect on normal lymphoid cells of the
      thymus or spleen. 4-HPR and its stereoisomer, 9-cis-4-HPR, are 50 to > 150 times
      more potent than 7 other retinoids in killing CEM-C7 human T lymphoblastoid
      leukemia cells and P1798-C7 murine T lymphoma cells. 4-HPR's apoptotic action
      requires the intact molecule bearing both the retinoid moiety and the
      hydroxyphenol ring; 4-HPR remains unmetabolized after uptake into CEM-C7 and
      P1798-C7 cells for up to 24 hours. We also show that glucocorticoid (GC)
      resistant variants are equally susceptible to 4-HPR as are GC-sensitive cells.
      Thus, 4-HPR may be potentially important as a new chemotherapeutic drug for use
      as alternative to, or in combination with, conventional drugs for treating
      lymphoid malignancies.

PMID- 9168438
TI  - c-kit Point mutation in patients with myeloproliferative disorders.
AB  - Myeloproliferative disorders (MPD) constitute a group of hematopoietic neoplasms
      at the myeloid stem cell level. Myeloid stem cells and/or progenitor cells from
      MPD have been considered sensitive to hematopoietic growth factors, including
      erythropoietin, thrombopoietin and stem cell factor (SCF). SCF is a ligand for c
      kit receptor with tyrosine kinase. We analysed the gene alteration of the c-kit
      extracellular domain in MPD patients by PCR-SSCP and subsequent nucleotide
      sequencing. The point mutation in the N-terminal part of the domain, codon 52
      (Asp-->Asn), was found in two patients with primary myelofibrosis and one with
      chronic myelogenous leukemia. We review the literature regarding the role of
      SCF/c-kit system in the oncogenesis of leukemia and MPD, and then discuss the
      significance of our finding in the context of growth advantage of the mutated
      clones over the normal clones.

PMID- 9168439
TI  - Placebo-controlled phase III study of lenograstim (glycosylated recombinant human
      granulocyte colony-stimulating factor) in aggressive non-Hodgkin's lymphoma:
      factors influencing chemotherapy administration. Groupe d'Etude des Lymphomes de
      l'Adulte.
AB  - The purpose of this study was to, assess the efficacy of glycosylated recombinant
      human granulocyte colony-stimulating factor (lenograstim) in the prevention of
      neutropenia and infection in patients receiving dose-intensive chemotherapy for
      non-Hodgkin's lymphoma (NHL). A second objective was to determine clinical
      predicators of delay to cytotoxic chemotherapy administration. One hundred-sixty
      two patients with intermediate- or high-grade NHL and at least one poor
      prognostic factor received a total of 4 cycles of the LNH-84-regimen every 2
      weeks, with an open randomization to treatment with anthracyclines. Patients were
      randomized to receive subcutaneous lenograstim 5 micrograms/kg/day (n = 82) or
      placebo (n = 80) from day 6 to day 13 of each cycle. The incidence of severe
      neutropenia (absolute neutrophil count (ANC) < 0.5 x 10(9)/L) was reduced in the
      lenograstim group compared with placebo (52% vs 75%). A significant reduction (p
      < 0.001) in the median duration of ANC < 0.5 x 10(9)/L was also observed in
      patients treated with lenograstim during each cycle of chemotherapy (0-1 day vs 2
      4 days in placebo recipients). Fever occurred in 66 patients in each treatment
      group. Thirty-four percent of placebo recipients had documented infections during
      ANC < 1.0 x 10(9)/L compared with 18.5% of lenograstim-treated patients (p <
      0.05). Infections of > or = 2 severity were significantly less frequent (p =
      0.001) among lenograstim recipients compared with placebo (25 vs 49). The most
      common adverse events among lenograstim recipients were headache, mild bone pain
      and injection site reactions. Although lenograstim significantly increased (p =
      0.0001) relative dose intensity compared with placebo (93% vs 80%), no difference
      in CR rate (67% vs 71%) or 3-year survival (63% vs 55%) was observed. The results
      of this study suggest that patients treated with a chemotherapy regimen that
      induces severe neutropenia can benefit from treatment with lenograstim.
      Furthermore, lenograstim permits treatment to be delivered at full dose intensity
      at 2 week intervals, even in patients with bone marrow involvement, and may
      permit further dose escalation of the chemotherapeutic regimen used.

PMID- 9168440
TI  - Phenotypic analysis of receptor-ligand pairs on B-cells in B-chronic lymphocytic
      leukemia.
AB  - Whole-blood three-color immunofluorescence analysis was used to investigate the
      role of CD5/CD72 and CD21/CD23 receptor-ligand pair formation on B-chronic
      lymphocytic leukemia (B-CLL) cells as well as sCD23 and bcl-2 oncoprotein
      expression in disease progression and activity and total tumor mass in B-cell
      chronic leukemia (B-CLL) patients. Thirty-four patients with B-CLL and 19
      controls were included in the study. The majority of B-cells in B-CLL patients
      coexpressed CD5 and CD72 as well as the CD23 antigen. Unlike B-cells in B-CLL
      patients, B-cells in all healthy controls tested had high expression of CD21
      antigen. We identified two groups of B-CLL patients according to high (n = 20) or
      low levels (n = 14) of CD21 expression on CD19+CD23+ B-cells. Only in the
      patients with high CD21 expression, were sCD23 levels positively correlated with
      factors known to have prognostic significance in B-CLL (Rai stage and TTM) and
      could, therefore, be used as a prognostic parameter for these B-CLL patients. Bcl
      2 oncoprotein expression did not differ between these patient groups. We presumed
      that in patients with a lower expression of CD21 antigen, the contribution of the
      CD21 molecule to homotypic adhesion was lacking. Further studies are necessary to
      determine the possible association of higher expression of the CD21 antigen with
      disease progression and the aggressive character of the B-CLL.

PMID- 9168441
TI  - Intermittent infusion of cladribine (CdA) in previously treated patients with low
      grade non-Hodgkin's lymphoma.
AB  - Thirty-six patients with previously treated low-grade non-Hodgkin's lymphoma (LG
      NHL) were included in a phase II study between August 1990 and February 1994 and
      treated with 0.12 mg/kg CdA as a 2 h.i.v. infusion daily x V, q 28 days up to 6
      courses. Twenty-three were refractory to previous chemotherapy while 13 were
      relapsed. Four patients had mantle cell lymphoma, 17 follicle centre cell derived
      lymphoma, 7 lymphoplasmacytoid lymphomas and, 8 had small lymphocytic lymphoma.
      The response rate was 42%, with 5 (14%) CR and 10 (28%) PR while 6 (16%) patients
      progressed during treatment. The median number of delivered CdA courses was 3 (1
      6) in non-responding cases and 6 (2-6) in responders. The median time to
      progression was 9 mo for all patients, 23 mo for CR and 16 mo for PR patients.
      Toxicity was sometimes severe with 3 infectious deaths (1 pneumocystis carinii
      pneumonia, 1 gram negative septicemia, and 1 fungal pneumonia), and 6 grade 3 or
      4 infectious episodes. We conclude that responses to CdA in this group of heavily
      pre-treated patients is impressive. However, toxicity is considerable and the
      rate of opportunistic infections is worrisome.

PMID- 9168442
TI  - Dose escalation of epirubicin in the CEOP-BLEO regimen: a controlled clinical
      trial comparing standard doses for the treatment of diffuse large cell lymphoma.
AB  - One hundred and forty-seven consecutive patients with previously untreated high
      intermedium and high clinical risk diffuse large cell lymphoma (DLCL) were
      included in a prospective clinical trial to evaluate the efficacy and toxicity of
      escalating doses of epirubicin compared to standard doses in the CEOP-Bleo
      (cyclophosphamide, epirubicin, vincristine and prednisone and bleomycin) regimen,
      55% of the patients were > 60 years old and most patients had adverse prognostic
      factors at diagnosis. Complete response rates were similar in both groups (68% in
      the standard dose compared to 73% in the escalating arm, (p = 0.5). However, time
      to treatment failure (TFF) and overall survival were better after escalating
      doses. At 3-years TTF at a medial follow-up of 33.6 months was 76% in the
      patients whose received escalating dose statistical different to 37% of the
      patients whose received standard doses (p < .01). Overall survival was 81% in the
      escalated therapy arm which is statistical different to 40% of the patients
      treated with standard doses (p < .01). Toxicity was mild in both arms.
      Neutropenia, mucositis and cardiotoxicity were mild in the escalated dose arm and
      no severe complications were observed. All patients received the planned doses of
      all drugs. Patients > 60 years old had the same CR rate, TTF and overall survival
      as younger patients. In conclusion it seems that the dose of epirubicin can be
      increased in combination chemotherapy regimens with safety and only mild
      toxicity. The CR rate was not superior compared to the standard dose but the TTF
      and overall survival were better. Longer follow-up periods are required in order
      to determine if the cure rate can also be improved. Older patients can also
      benefit because they also tolerated the increase in epirubicin without severe
      side effects and also improved their outcome. The use of more aggressive regimens
      with increase in dose intensity may be the treatment of choice for more patients
      poor prognosis, with DLCL provided there is no increase in toxicity. In this
      respect the use of epirubicin in higher doses/appears to be useful.

PMID- 9168443
TI  - Low levels of serum soluble c-kit relates to delayed engraftment after bone
      marrow transplantation.
AB  - Serum soluble c-kit concentrations were measured in 28 patients undergoing bone
      marrow transplantation (BMT). The c-kit levels in patients with delayed
      engraftment (time to leukocyte recovery > 1.0 x 10(9)/L being more than 20 days
      after BMT) were significantly lower than those in patients with early engraftment
      (time to leukocyte recovery being less than 19 days after BMT) from the start of
      conditioning until day 100 after BMT. The data from this study indicates that the
      measurement of serum soluble c-kit concentrations may be a useful indicator of
      engraftment.

PMID- 9168445
TI  - In vitro culture studies of childhood myelodysplastic syndrome: establishment of
      the cell line MUTZ-1.
AB  - Myelodysplastic syndrome (MDS) in childhood is considered to be very rare and
      detailed pathobiological data are scarce. More biological information regarding
      MDS in children is clearly needed and in vitro culture studies provide one
      possibility for gaining further pathophysiological insights into this malignancy.
      Here, we incubated bone marrow samples from 30 children with MDS in liquid
      suspension culture in order to grow the transformed cells in vitro. In most
      cultures, the hematopoietic cells died quickly and only fibroblastic (stromal)
      background layers proliferated temporarily; several normal Epstein-Barr virus
      (EBV)-transformed B-lymphoblastoid cell lines (B-LCL) were established. Only in
      one instance, albeit from the peripheral blood and not from the bone marrow,
      could we establish a cell line, termed MUTZ-1, from the malignant cells of a 5
      year-old girl with MDS (FAB subtype refractory anemia with excess of blasts). The
      MDS arose from a pre-existing Fanconi anemia and progressed quickly to an acute
      myeloid leukemia (FAB M2). Despite positivity for EBV, MUTZ-1 is not an EBV + B
      LCL and further characterization of MUTZ-1 confirmed the derivation from the
      transformed clonal cells. Immunophenotyping showed a pre B-cell surface marker
      profile (CD10+ CD19+ cytoplasmic IgM+); receptor gene rearrangement analyses
      underlined the clonal B-cell nature of MUTZ-1 cells. MUTZ-1 cells exhibit a
      highly rearranged, unstable karyotype with a high frequency of spontaneous
      chromatid breaks and exchanges; del(5q) and additional rearrangements involving
      chromosome 5 [der(15)t(5;15)] were detected. The present data and results from a
      few other MDS-derived cell lines suggest that the transforming event in MDS seems
      to occur in an immature pluripotent progenitor cell. The new MDS-derived
      continuous cell line MUTZ-1 provides a useful in vitro model system for studies
      on the pathogenetic events leading to MDS.

PMID- 9168444
TI  - Induction of polyploidization in the human erythroleukemia cell line (HEL) by
      protein kinase inhibitor (K252a) and the phorbol-ester TPA.
AB  - Endomitosis (polyploidization) is a distinctive feature of megakaryocyte
      differentiation. We examined this mechanism in an erythromegakaryocytic cell
      line, HEL, using a protein kinase inhibitor K252a or a phorbol-ester TPA. HEL
      cells treated with K252a showed a marked increase in the proportion of CD41
      positive cells and polyploid cells as well as in cellular size and nuclear size.
      TPA showed similar results but induced multi-nucleation instead of enlargement of
      nuclear size. K252a added at the G1/S boundary phase did not inhibit the first
      and second round DNA synthesis, but inhibited cell division. K252a did not
      inhibit the expression of genes involved in mitosis such as cyclin B, cdc25B and
      cdc2, in the first round S phase. However, the cyclin B associated Cdc2 kinase
      activity needed for mitosis during the G2/M phase was reduced by K252a. TPA
      delayed DNA synthesis and expression of these genes, and suppressed Cdc2 kinase
      activity in the second round G2/M phase. These results suggest that the
      polyploidization induced by K252a results from inhibiting mitosis possibly caused
      by suppression of Cdc2 kinase activity. TPA may induce the multi-nucleation
      through a different mechanism.

PMID- 9168446
TI  - Idarubicin and intermediate dose ARA-C followed by consolidation chemotherapy or
      bone marrow transplantation in relapsed or refractory acute myeloid leukemia.
AB  - Sixty-one adult patients with relapsed or refractory acute myelogenous leukemia
      (AML) were treated in a cooperative study with Idarubicin 12 mg/m2/day on days 1
      to 3 and AraC 1 g/m2/12h on days 1 to 4. Responding patients were scheduled for
      consolidation with Ida-IDAraC and bone marrow transplantation (BMT) when
      feasible. Twelve of 23 refractory patients (52%) and 21 of 38 relapsed patients
      (55%) achieved complete remission (CR). Refractory patients treated very early
      with Ida-IDAraC (CR 63%) and relapsed patients with initial CR > 6 months (CR
      68%) were the subgroups with better CR rate. The only factor influencing the
      disease free survival (DFS) was the intensity of postremission therapy: Nine
      patients had severe toxicity with the salvage regimen and were excluded for
      consolidation, fourteen patients received Ida-IDAraC and ten patients proceeded
      to myelo-ablative therapy supported with autologous or allogeneic BMT. The three
      groups had different median DFS of 6 months, 9 months and 15 months respectively
      (P = 0.017). In summary, Ida-AraC is an efficient salvage regimen for AML. The CR
      rate seems to be improved in refractory patients if used promptly, but the long
      term outcome appears to depend on the intensity of treatment given once remission
      is achieved and on the ability to perform BMT.

PMID- 9168447
TI  - Establishment of a new cell line from a patient with hairy cell leukemia-Japanese
      variant.
AB  - A cell line, JHC-2, was established from the peripheral blood of a patient with
      hairy cell leukemia (HCL)-Japanese variant. The JHC-2 cells have cytologic
      features similar to those of the original tumor cells. They displayed hairy
      cytoplasmic projections by phase contrast and scanning electron microscopy. The
      tartrate-resistant acid phosphatase reaction was weakly positive. The
      immunophenotype of the JHC-2 cells was CD5-, CD10-, CD11c+/-, CD19+, CD21+,
      CD23+, CD24-, CD25+/-, CD38- and FMC-7+. The expression of surface immunoglobulin
      (IgG, kappa) and the configuration of Ig gene rearrangements in the JHC-2 cells
      were identical to those in the original leukemic cells, and the JHC-2 cells
      displayed trisomy 9 on cytogenetic examination. Southern blot analysis for the
      Epstein-Barr virus (EBV) genome showed that the JHC-2 cells contained the EBV
      genome, although the freshly isolated leukemic cells did not. These results
      indicate that the JHC-2 cell line is an EBV spontaneously transformed B cell line
      originating from HCL cells.

PMID- 9168448
TI  - Hairy cell leukemia-variant treated with 2-chlorodeoxyadenosine--a report of
      three cases.
AB  - Three patients with B-prolymphocytic variant of HCL (HCL-V) were treated with a
      chlorinated purine analogue, 2-chlorodeoxyadenosine, at a daily dosage of 0.12
      mg/kg in 2-hour intravenous infusion for 5 consecutive days. Partial remission
      was achieved in only 1 patient, who relapsed after 6 months. Two other patients
      did not respond to the treatment. HCL-V is a distinct clinicopathological entity
      which seems to be resistant to various therapeutic modalities. However, further
      observations are necessary in order to establish the efficacy of 2-CdA in the
      treatment of HCL-V.

PMID- 9168449
TI  - Aggressive natural killer (NK) cell lymphoma: report of a pediatric case and
      review of the literature.
AB  - We report a rare pediatric case of aggressive natural killer (NK) cell lymphoma,
      characterized by acute onset hepatosplenomegaly and respiratory distress, and
      infiltration by large granular lymphocytes with the phenotype of CD3-CD16-CD56+.
      The patient has remained in complete remission after short-pulse intensive
      chemotherapy, and myeloablative therapy followed by allogeneic bone marrow
      transplantation. We compare our case with 7 other children with NK cell leukemia
      reported from other institutions.

PMID- 9168450
TI  - Facial heliotrope rash as the initial manifestation of acute myelomonocytic
      leukemia.
AB  - The association of leukocytoclastic vasculitis or dermatomyositis with
      malignancies has been reported. We describe a patient who developed a skin rash,
      histologically compatible with dermatomyositis, which during the course of the
      disease switched to leukocytoclastic vasculitis, which was accompanied with
      peripheral blood pancytopenia in the absence of any specific pathological
      manifestation from the bone marrow three years prior to the diagnosis of acute
      myelomonocytic leukemia (AMML).

PMID- 9168451
TI  - Translocation t(4;11)(q21;q23) and MLL gene rearrangement in acute lymphoblastic
      leukemia secondary to anti topoisomerase II anticancer agents.
AB  - Secondary therapy-related, acute lymphoblastic leukemia (S-ALL) is less common
      than its myeloblastic counterpart. S-ALL with MLL gene rearrangements have only
      been reported on six previous occasions. Only three of these had t(4;11)(q21;23)
      S-ALL with MLL-AF4 fusion transcript has only been reported in one earlier case.
      In this report a rare case of S-ALL with MLL-AF4 transcript is described in a 36
      year old woman treated for breast carcinoma with chemotherapy which included the
      topoisomerase II inhibitor, VP-16. The precise incidence of MLL gene
      rearrangement in S-ALL still remains to be clarified.

PMID- 9168452
TI  - Age-related changes in catalytic activity, enzyme mass, mRNA, and subcellular
      distribution of hepatic neutral cholesterol ester hydrolase in female rats.
AB  - Activity and protein mass of hepatic neutral cholesteryl ester hydrolase (CEH)
      were measured in liver cytosol and washed microsomes of female Sprague-Dawley
      rats aged 3, 4, 7, 9, 13, and 16 wk. CEH mRNA was also measured. The microsomal
      component varied with age and contributed a greater fraction of total activity in
      females than previously reported in males. Nevertheless, the cytosolic component
      accounted for 62-80% of activity and 77-94% of immunoreactive protein in
      postmitochondrial fractions. Cytosolic and microsomal CEH specific activities,
      relative to total protein, decreased 94 and 83%, respectively, from 3 to 4 wk,
      prior to onset of puberty at 5 wk, and increased 360 and 137%, respectively, from
      12 to 16 wk. These results contrast with an earlier study, in which cytosolic CEH
      activity of males increased with puberty and declined after 12 wk. Although
      cytosolic CEH was activated by protein kinase A and inhibited by alkaline
      phosphatase treatment at all ages, protein kinase activation peaked at 4 wk,
      coinciding with the initial decrease in specific activity. Specific activity in
      cytosol and microsomes correlated with CEH mass at all ages, suggesting that this
      CEH accounts for most variation in cellular activity. In contrast, CEH mRNA
      varied little from 3-16 wk, indicating that transcriptional regulation does not
      make a major contribution to the variation in CEH activity and mass in females,
      although it may make an important contribution to male-female differences in CEH
      expression. Specific activities of cytosolic and microsomal CEH, relative to
      immunoreactive CEH protein mass, exhibited changes consistent with
      posttranslational regulation. These results indicate gender-specific multivalent
      regulation of hepatic CEH by posttranslational mechanisms during development of
      female rats.

PMID- 9168453
TI  - Metal ion stimulation of phospholipase D-like activity of isolated rat intestinal
      mitochondria.
AB  - Presence of phospholipase D-like (PLD) activity in the intestinal mitochondria
      was identified using endogenous phospholipids as substrate. The enzyme had a pH
      optimum of 6.5, did not show trans-phosphatidylation activity in the presence of
      ethanol or butanol, and the product formed was phosphatidic acid (PA). This was
      confirmed by separation of reaction products by high-performance liquid
      chromatography and analysis of composition of the PA formed which gave
      phosphate/fatty acid ratio of 1:2 PLD-like activity was further confirmed by the
      formation of ethanolamine and choline as products of enzyme action. This activity
      was stimulated by various metal ions; when stimulated by Mg2+ and Ba2+, it
      hydrolyzed both phosphatidylcholine and phosphatidylethanolamine, and when
      stimulated by Ca2+, it preferentially hydrolyzed phosphatidylethanolamine. There
      was no requirement for sodium oleate for the PLD-like activity in mitochondria.
      These results suggest that intestinal mitochondria have an active PLD-like enzyme
      which differs in certain properties from phospholipase D from other tissues.

PMID- 9168454
TI  - Membrane lipid metabolism and phospholipase activity in insect Spodoptera
      frugiperda 9 ovarian cells.
AB  - Although there is increasing use of insect ovarian Sf9 cells for the production
      of recombinant proteins, namely, via the baculovirus vector expression system,
      little is known about the lipids in the cell membrane and whether endogenous
      phospholipases are present for regulation of the cell membrane lipids. In this
      study, analysis of membrane lipids of Sf9 cells indicated the presence of
      phosphatidylethanolamine (PE) (diacyl type) and phosphatidylcholine as major
      phospholipids, followed by phosphatidylserine and phosphatidylinositol (PI), and
      only trace amounts of ethanolamine plasmalogen. These phospholipids contain high
      proportions of monoenoic fatty acids, e.g., 16:1 and 18:1, which comprise more
      than 70% of the total fatty acids although small amounts of polyunsaturated fatty
      acids such as 18:2 and 20:4 are also present. When Sf9 cells were incubated in a
      culture medium containing [14C]oleic acid and [14C]arachidonic acid, a large
      portion of the labels were incorporated into membrane phospholipids. Using
      [14C]arachidonoyl-phospholipids as substrates for incubation with cell homogenate
      and subcellular fractions, results indicate the presence of a ca(2+)-independent
      phospholipase A (PLA2) in the Sf9 cell cytosol fraction. This PLA2 shows a high
      preference for hydrolysis of PE and is active at a pH range of 7-9. Unlike the
      brain cells which contain active phospholipase C (PLC) specific for
      phosphatidylinositol, only limited amount of diacylglycerol (DAG) was released
      from [14C]arachidonoyl-PE in the Sf9 cells. Taken together, this study
      demonstrates active metabolism of membrane phospholipids in Sf9 cells, most
      likely mediated by acyltransferases and PLA2. Furthermore, despite the absence of
      PLC for PI, limited amount of DAG could be generated through hydrolysis of PE.

PMID- 9168455
TI  - Biosynthesis of medium-chain triacylglycerols and phospholipids by HepG-2 cells.
AB  - In an attempt to understand the metabolism by the liver of fatty acids (FA) of
      different chain length, we have studied the incorporation of [1(-14)C]-labeled
      C2, C8, C10, C12, and C16 into cellular lipids by HepG-2 cells. Over 90% of the
      radiolabeled FA were detected in phospholipids (PL) and triacylglycerols (TAG).
      The incorporation of C12 and C16 was three to four times higher than that of C8
      and C10 (and reached 35 nmoles per mg protein after 1.5 h). The radioactivity of
      C2, C8, and C10 was recovered mainly in PL. C12 and C16 were incorporated at
      approximately equal amounts into PL and TAG. The radioactivity of both C2 and C8
      was recovered exclusively in long-chain FA, suggesting oxidation of C8 into C2
      units prior to FA synthesis. C10 likewise yielded mainly long-chain FA. However
      10% of unchanged C10 was found in PL and up to 30% in TAG. 14C-C12 was largely
      incorporated unchanged. Under these conditions, the presence of C10 and C12 in PL
      and TAG was shown also by gas-liquid chromatography. In the presence of either
      C2, C8, or C10, up to 30% of 14C-monounsaturated FA were detected in PL and TAG.
      With C12 and C16, the fraction of 14C-monounsaturated FA was much smaller
      suggesting that extensive desaturation occurred during de novo synthesis.

PMID- 9168456
TI  - Effect of docosahexaenoic acid on mouse mitochondrial membrane properties.
AB  - Long-chain polyunsaturated (n-3) fatty acids have been proposed to be involved in
      a wide variety of biological activities. In this study, mitochondrial
      docosahexaenoic acid (DHA) levels were increased by either dietary manipulation
      or by fusing the mitochondria with phospholipid vesicles made from 1-stearoyl-2
      docosahexaenoyl-sn-glycero-3-phosphocholine (18:0/22:6 PC). The fused
      mitochondria exhibited a DHA-induced decrease in respiratory control index (RCI)
      and membrane potential and an increase in proton movement. The modified
      mitochondria also demonstrated an increase in fluidity (as detected by 1,6
      diphenyl-1,3,5-hexatriene anisotropy) and changes in membrane structure detected
      by the fluorescence probes MC540 and pyrene decanoate. Proton movement in lipid
      vesicles made from mitochondrial lipid extracts was shown to be enhanced by
      incorporated 18:0/22:6 PC. Mitochondria were isolated from young (5-mon) and old
      (24-mon) mice which were maintained on either a diet rich in saturated fats
      (hydrogenated coconut oil) or rich in n-3 polyunsaturated fats (menhaden oil).
      Mitochondrial bioenergetic function was followed by RCI, state 3 respiration, ATP
      level, and phosphate uptake. In addition, lipid composition, phospholipid
      area/molecule and extent of lipid peroxidation were also determined. Decreases in
      RCI for the menhaden oil diet-modified mitochondria paralleled those in which DHA
      levels were enhanced by fusion with phospholipid vesicles. RCI reductions are
      attributed to DHA-induced increases in H+ movement, producing diminished
      mitochondrial membrane potentials. One purpose of this project was to determine
      if the deleterious effects of aging on mitochondrial bioenergetic function could
      be reversed by addition of n-3 fatty acids. The experiments reported here
      indicate that incorporation of long-chain polyunsaturated n-3 fatty acids into
      mitochondrial membranes does not appear likely to reverse the effects of age on
      mitochondrial function.

PMID- 9168457
TI  - Molecular species of phosphoglycerides in liver microsomes of rats fed a fat-free
      diet.
AB  - The influence of a fat-free diet on the molecular species composition of
      phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol
      (PI) of rat liver microsomes was studied by using reversed-phase high-pressure
      liquid chromatography. In the three phosphoglyceride classes analyzed, the fat
      free diet produced a large decrease in the 18:0/20:4n-6 species but less
      important changes were found in the 16:0/20:4n-6 species. In PC, the most
      abundant phosphoglyceride class of rat liver microsomes, the fall in the
      18:0/20:4n-6 species was counterbalanced mainly by an enhancement in the
      16:0/18:1n-9 species although it was not evident in PE. In PI, the decrease in
      the 18:0/20:4n-6 species was counterbalanced by an increase in the 18:0/20:3n-9
      species. Fluorescence polarization measurements of 1,7-diphenyl-1,3,5-hexatriene
      in liposomes of 16:0/18:1n-9, 18:0/18:1n-9-, 16:0/20:4n-6-, and 18:0/20:4n-6-PC
      indicated that the change in the saturated fatty acid in the sn-1 position
      accompanying the replacement of 20:4n-6 by 18:1n-9 could be very important for a
      homeoviscous compensation, maintaining the membrane physical properties without
      large alterations in spite of the essential fatty acid deficiency due to the fat
      free diet.

PMID- 9168458
TI  - The effect of dietary lipid on polyunsaturated fatty acid metabolism in Atlantic
      salmon (Salmo salar) undergoing parr-smolt transformation.
AB  - The aim of this study was to measure the changes in lipid metabolism which occur
      during smoltification and seawater transfer in Atlantic salmon (Salmo salar).
      Duplicate groups of Atlantic salmon parr were fed diets containing either fish
      oil (FO) or a blend of linseed and rapeseed oils, vegetable oil (VO), from
      October (week 0) to seawater transfer in May (week 26). From May to August (weeks
      26-43), all fish were fed a fish oil-containing diet. Fatty acyl desaturation and
      elongation activity were followed in isolated hepatocytes incubated with
      radioactive 18:3n-3 and 18:2n-6. Metabolism of 18:3n-3 was consistently around 5
      fold greater than metabolism of 18:2n-6, and total metabolism of both substrate
      polyunsaturated fatty acids (PUFA) was increased in fish fed both VO and FO up to
      seawater transfer after which desaturation activities were reduced. Desaturation
      activities with both 18:3n-3 and 18:2n-6 were significantly greater in fish fed
      VO, compared to fish fed FO, at 22 and 26 wk. Arachidonic acid (20:4n-6; AA) in
      liver polar lipids (PL) of fish fed VO increased consistently from weeks 0-22 but
      varied after seawater transfer. In fish fed FO, AA in liver PL remained constant
      up to week 17 before increasing at seawater transfer and leveling off thereafter.
      Eicosapentaenoic acid (20:5n-3; EPA) in liver PL of fish fed VO decreased
      significantly from week 0-22 before rising at seawater transfer and increasing
      rapidly posttransfer. EPA in liver PL of fish fed FO showed a similar trend
      except EPA was always greater in the freshwater phase compared to fish fed VO.
      Docosahexaenoic acid (DHA) levels in liver PL of fish fed VO remained constant in
      the seawater phase before increasing following seawater transfer. In fish fed FO,
      DHA in liver PL increased from weeks 0-17 reducing and leveling off postseawater
      transfer. The levels of PGF(2 alpha) and PGF(3 alpha) were measured in isolated
      gill cells stimulated with calcium ionophore A23187. PGF(2 alpha) production in
      fish fed VO increased significantly between 0-7 wk before decreasing toward
      seawater transfer. After transfer, PGF(2 alpha), production increased to a peak
      at 35 wk. PGF(2 alpha) production in fish fed FO was not significantly altered
      during the trial period. The changes in PGF(3 alpha) production were broadly
      similar to those occurring with PGF(2 alpha), but the latter was always in excess
      of the former (2- to 4-fold). Plasma chloride concentrations in fish subjected to
      seawater challenge at 20 wk were significantly lower in fish fed VO compared to
      those fed FO. This study has provided new information on the changes in lipid
      metabolism which accompany parr-smolt transformation and suggests that diets
      which have a fatty acid composition more similar to that in aquatic invertebrates
      may be beneficial in effecting successful seawater adaptation.

PMID- 9168459
TI  - Modifying the n-3 fatty acid content of the maternal diet to determine the
      requirements of the fetal and suckling rat.
AB  - During perinatal development, docosahexaenoic acid (22:6n-3) accumulates
      extensively in membrane phospholipids of the nervous system. To evaluate the n-3
      fatty acid requirements of fetal and suckling rats, we investigated the
      accumulation of 22:6n-3 in the brain and liver of pup rats from birth to day 14
      postpartum when their dams received increasing amounts of dietary 18:3n-3 (from 5
      to 800 mg/100 g diet) during the pregnancy-lactation period. The fatty acid
      composition of brain and liver phospholipids of pups, as well as that of dam's
      milk, was determined. At birth, 22:6n-3 increased regularly to reach the highest
      level when the maternal diet contained 800 mg 18:3n-3/100 g. On days 7 and 14
      postpartum, brain 22:6n-3 plateaued at a maternal dietary supply of 200 mg/100 g.
      Docosapentaenoic acid (22:5n-6) had the opposite temporal pattern. The unusually
      high concentration of eicosapentaenoic acid (20:5n-3) in liver and dam's milk
      observed at the highest 18:3n-3 intake suggests an excessive dietary supply of
      this fatty acid. All these data suggest that the n-3 fatty acid requirements of
      the pregnant rat are around 400 mg 18:3n-3 and those of the lactating rat at 200
      mg (i.e., 0.9 and 0.45% of dietary energy, respectively). The values of 18:3n-3
      and 22:6n-3 milk content which allowed brain 22:6n-3 to reach a plateau value in
      suckling pups were 1% of total fatty acids and 0.9% (colostrum) to 0.2% (mature
      milk), respectively. These levels are similar to those recommended for infant
      formulas.

PMID- 9168460
TI  - Lipid peroxidation during n-3 fatty acid and vitamin E supplementation in humans.
AB  - The purpose of this study was to investigate in healthy humans the effect of
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake, alone or in
      combination with dL-alpha-tocopherol acetate (vitamin E) supplements on lipid
      peroxidation. Eighty men were randomly assigned in a double-blind fashion to take
      daily for 6 wk either menhaden oil (6.26 g, n-3 fatty acids) or olive oil
      supplements with either vitamin E (900 IU) or its placebo. Antioxidant vitamins,
      phospholipid composition, malondialdehyde (MDA), and lipid peroxides were
      measured in the plasma at baseline and week 6. At the same time, breath alkane
      output was measured. Plasma alpha-tocopherol concentration increased in those
      receiving vitamin E (P < 0.0001). In those supplemented with n-3 fatty acids, EPA
      and DHA increased in plasma phospholipids (P < 0.0001) and plasma MDA and lipid
      peroxides increased (P < 0.001 and P < 0.05, respectively). Breath alkane output
      did not change significantly and vitamin E intake did not prevent the increase in
      lipid peroxidation during menhaden oil supplementation. The results demonstrate
      that supplementing the diet with n-3 fatty acids resulted in an increase in lipid
      peroxidation, as measured by plasma MDA release and lipid peroxide products,
      which was not suppressed by vitamin E supplementation.

PMID- 9168462
TI  - Structure analysis of an allene-containing estolide tetraester triglyceride in
      the seed oil of Sebastiana commersoniana (Euphorbiaceae).
AB  - The seed oil of Sebastiana commersoniana (Euphorbiaceae) was separated into
      triglyceride and an estolide fraction by preparative thin-layer chromatography.
      The triglyceride band was characterized by spectroscopic methods, and its fatty
      acids have been analyzed by gas chromatography (GC) and GC-mass spectrometry (MS)
      as their methyl esters. Linolenic acid was the main fatty acid (65%). The
      estolide band was examined by a combination of spectroscopic and chromatographic
      methods (ultraviolet, infrared, nuclear magnetic resonance, fast atom bombardment
      MS, GC-MS of the fatty acids before and after silylation) and was identified as a
      tetraglyceride, where one alpha-carbon of the triglyceride backbone was esterfied
      with 8-hydroxy-5,6-octadienoic acid, which itself was esterfied with trans-2,cis
      4-decadienoic acid. The remaining positions of the triglyceride backbone were
      occupied by common fatty acids.

PMID- 9168461
TI  - The pharmacokinetics of water-in-oil-in-water-type multiple emulsion of a new
      tacrolimus formulation.
AB  - We developed a water-in-oil-in-water-type (W/O/W)-type multiple emulsion of a new
      tacrolimus formulation. A potential approach to avoid the complications of
      systemic immunosuppression and simultaneously enhance immunosuppressive efficacy
      is to deliver immunosuppressive agents locally to the site of the target organs.
      The W/O/W emulsion is dispersed oil drops containing smaller water droplets that
      allow the delivery of drugs preferentially to the reticuloendothelial systems
      (RES). Since the liver and the spleen are primary components of the RES, and the
      brain and the kidney have a poor RES, we hypothesized that a W/O/W emulsion of
      tacrolimus would possess the pharmacokinetic benefits of local immunosuppression.
      We evaluated this hypothesis in a rat model. The tacrolimus levels of whole
      blood, the liver, spleen, brain, and kidney in rats given intravenous emulsions
      of tacrolimus (W/O/W group) were compared with a group administered tacrolimus
      alone (T group). There were no significant differences between the
      pharmacokinetic parameters of W/O/W group and T group based on whole blood data.
      However, the W/O/W group had significantly decreased tacrolimus levels in the
      brain and kidney, and significantly increased levels in the liver and spleen
      compared with the T group. These data suggest that the W/O/W emulsion is
      applicable as an intravenous drug carrier for local immunosuppression.

PMID- 9168463
TI  - Nonionic surfactants regioselective synthesis of fatty acid esters of alpha- and
      beta-glucopyranose.
AB  - Lipophilic esters of saccharides belong to the family of nonionic surfactants
      widely employed in pharmaceutical and cosmetics formulations. A very simple
      method is presented whereby 6-O-esters of alpha- and beta-glucose can be prepared
      and isolated. Good results have been obtained in the synthesis of 6-O-oleyl
      derivatives by simple acylation with appropriate oleyl chloride. The condensing
      agent bis(2-oxo-3-oxazolidinyl) phosphinic chloride (BOP-Cl) allows the
      preparations of the same esters with better regioselectivity but with yields
      strongly dependent on the aliphatic chain length of the carboxylic acids
      employed.

PMID- 9168464
TI  - Novel fatty acid esters of (7E, 12E, 18R, 20Z)-variabilin from the marine sponge
      Ircinia felix.
AB  - The methanolic extract of the marine sponge Ircinia felix has yielded nine novel
      fatty acid esters, (7E, 12E, 18R, 20Z)-variabilin (5Z, 9Z)-22
      methyltricosadienoate, (7E, 12E, 18R, 20Z)-variabilin (5Z, 9Z)-tetracosadienoate,
      (7E, 12E, 18R, 20Z)-variabilin hexadecanoate, (7E, 12E, 18R, 20Z)-variabilin 10
      methylhexadecanoate, (7E, 12E, 18R, 20Z)-variabilin 15-methylhexadecanoate, (7E,
      12E, 18R, 20Z)-variabilin 14-methylhexadecanoate, (7E, 12E, 18R, 20Z)-variabilin
      9-octadecenoate, (7E, 12E, 18R, 20Z)-variabilin octadecanoate, and (7E, 12E, 18R,
      20Z)-variabilin 2,11-dimethyloctadecanoate, along with the recently described
      (7E, 12E, 18R, 20Z)-variabilin 11-methyloctadecanoate. The characterization of
      the new fatty acids (5Z, 9Z)-22-methyltricosadienoic and 2,11
      dimethyloctadecanoic acids is also described. The chemical structures were
      determined by extensive spectroscopic, chromatographic, and chemical analyses.

PMID- 9168465
TI  - Multiple systems for recognition of apoptotic lymphocytes by macrophages.
AB  - In vivo, apoptotic lymphocytes are recognized and phagocytosed by macrophages
      well before the final stages of DNA degradation and cell lysis. The recognition
      process is apparently triggered by the exposure of phosphatidylserine (PS) on the
      cell surface, an event which precedes cell lysis by several hours. However,
      multiple receptors appear to respond to this event. We demonstrate here that both
      activated and unactivated macrophages recognize PS, but with different receptor
      systems. Phagocytosis of apoptotic lymphocytes by activated (but not by
      unactivated) macrophages is inhibited by pure PS vesicles as well as by N
      acetylglucosamine, implicating involvement of a lectin-like receptor in this
      case. Conversely, uptake of apoptotic lymphocytes by unactivated (but not by
      activated) macrophages is inhibited by PS on the surface of erythrocytes as well
      as by the tetrapeptide RGDS and cationic amino acids and sugars, implicating
      involvement of the vitronectin receptor in this case. Recognition by both classes
      of macrophages is blocked by the monocyte-specific monoclonal antibody 61D3. The
      signal recognized by activated macrophages appears to develop on the lymphocyte
      prior to assembly of the signal recognized by unactivated macrophages.
      Collectively, these results suggest that PS exposure on the surface of apoptotic
      lymphocytes generates a complex and evolving signal recognized by different
      receptor complexes on activated and unactivated macrophages.

PMID- 9168466
TI  - Positive and negative tissue-specific signaling by a nematode epidermal growth
      factor receptor.
AB  - The major determinants of receptor tissue tyrosine kinase (RTK) signaling
      specificity have been proposed to be Src homology 2 (SH2) binding sites,
      phosphotyrosine-containing oligopeptides in the cytoplasmic domain of the
      receptor. The Caenorhabditis elegans epidermal growth factor receptor homologue
      LET-23 has multiple functions during development and has eight potential SH2
      binding sites in a region carboxyl terminal to its kinase domain. By analyzing
      transgenic nematodes for three distinct LET-23 functions, we show that six of
      eight potential sites function in vivo and that they are required for most, but
      not all, of LET-23 activity. A single site is necessary and sufficient to promote
      wild-type fertility. Three other sites activate the RAS pathway and are involved
      only in viability and vulval differentiation. A fifth site is promiscuous and can
      mediate all three LET-23 functions. An additional site mediates tissue-specific
      negative regulation. Putative SH2 binding sites are thus key effectors of both
      cell-specific and negative regulation in an intact organism. We suggest two
      distinct mechanisms for tissue-specific RTK-mediated signaling. A positive
      mechanism would promote RTK function through effectors present only in certain
      cell types. A negative mechanism would inhibit RTK function through tissue
      specific negative regulators.

PMID- 9168468
TI  - Modulation of intracellular calcium levels inhibits secretion of collagenase 1 by
      migrating keratinocytes.
AB  - Calcium concentration influences keratinocyte differentiation, and, following
      injury, keratinocytes move through an environment of changing calcium levels.
      Because these migrating cells in wounds invariably express collagenase 1, we
      assessed if modulation of calcium levels regulates collagenase 1 production by
      primary human keratinocytes. Accurately reflecting the confined spatial pattern
      of enzyme production seen in vivo, collagenase 1 mRNA was expressed only by
      keratinocytes migrating from foci of differentiated cells. Treatment with calcium
      ionophores A23187 or thapsigargin markedly inhibited the basal and phorbol 12
      myristate 13-acetate-(PMA) stimulated accumulation of keratinocyte collagenase 1
      in the medium but did not affect collagenase 1 production by control or PMA
      treated fibroblasts. A23187-mediated inhibition of collagenase 1 protein was not
      associated with a decrease in mRNA levels but rather was controlled by a
      selective and reversible block of enzyme secretion. This block in secretion was
      likely not due to altered protein folding as the proenzyme within A23187-treated
      cells remained capable of autolytic activation upon treatment with p
      aminophenylmercuric acetate. In contrast, 92-kDa gelatinase mRNA and secreted
      protein levels were coordinately reduced by A23187. Keratin 14 expression, a
      basal keratinocyte marker, was reduced with PMA treatment, but A23187 did not
      affect keratin 14 expression. In human wounds, both basal and suprabasal
      keratinocytes at the migrating front of epidermis stained for keratin 14, but
      only the basal cells expressed collagenase 1. These data suggest that collagenase
      1 production is not necessarily linked with expression of basal cell markers and
      that modulation of intracellular calcium levels can block secretion of
      collagenase 1 by keratinocytes which have moved away from the stratum basalis and
      from their natural substrate.

PMID- 9168467
TI  - A role for HDJ-2/HSDJ in correcting subnuclear trafficking, transactivation, and
      transrepression defects of a glucocorticoid receptor zinc finger mutant.
AB  - All steroid receptors possess a bipartite nuclear localization signal sequence
      (NLS) that localizes within the second zinc finger of their DNA-binding domain.
      Fine-structure mapping of the rat glucocorticoid receptor (rGS) NLS identified a
      composite signal composed of three distinct proto-NLSs that function effectively
      when present in unique pairs. At least one of the rGR proto-NLSs appears to
      influence receptor trafficking within the nucleus, as revealed by a unique
      nuclear staining pattern of receptors possessing a point mutation (i.e., arginine
      at position 496; R496), at proto-NLS, pNLS-2. Specifically, carboxyl-terminal
      truncated rGRs possessing various point mutations at R496 localized within a
      limited number of large foci in nuclei of transiently transfected COS-1 cells.
      R496 mutations did not affect subnuclear targeting when present in full-length
      rGR, reflecting a protective effect of the receptor's ligand-binding domain that
      can be exerted in cis and in trans. The effects of rGR R496 mutations on
      subnuclear targeting were not autonomous because we also observed a coincident
      localization of hsp70, the 70-kDa heat shock protein, within nuclear foci that
      include r496 mutant receptors. The elimination of R496 mistargeting by
      overexpression of an hsp70 partner (i.e., the DnaJ homologue, HDJ-2/HSDJ)
      suggests that the hsp70/DnaJ chaperone system is mobilized to specific sites
      within the nucleus in response to inappropriate targeting or folding of specific
      mutant receptors. HDJ-2/HSDJ overexpression also corrects defective
      transactivation and transrepression activity of R496 mutant GRs. Thus, molecular
      chaperones, such as members of the hsp70 and DnaJ families, may survey the
      nucleus for misfolded proteins and actively participate in their refolding into
      biologically active conformational states.

PMID- 9168469
TI  - Isolation and molecular characterization of mRNA transport mutants in
      Schizosaccharomyces pombe.
AB  - Nucleocytoplasmic transport of mRNA is essential for eukaryotic gene expression.
      However, how mRNA is exported from the nucleus is mostly unknown. To elucidate
      the mechanisms of mRNA transport, we took a genetic approach to identify genes,
      the products of which play a role in that process. From about 1000 temperature 
      sensitive (ts- or cs-) mutants, we identified five ts- mutants that are defective
      in poly(A)+ RNA transport by using a situ hybridization with an oligo(dT)50 as a
      probe. These mutants accumulate poly(A)+ RNA in the nuclei when shifted to a
      nonpermissive temperature. All five mutations are tightly linked to the ts-
      growth defects, are recessive, and fall into four different groups designated as
      ptr 1-4 (poly(A)+ RNA transport). Interestingly, each group of mutants has a
      differential localization pattern of poly(A)+ RNA in the nuclei at the
      nonpermissive temperature, suggesting that they have defects at different steps
      of the mRNA transport pathway. Localization of a nucleoplasmin-green fluorescent
      protein fusion suggests that ptr2 and ptr3 have defects also in nuclear protein
      import. Among the isolated mutants, only ptr2 showed a defect in pre-mRNA
      splicing. We cloned the ptr2+ and ptr3+ genes and found that they encode
      Schizosaccharomyces pombe homologues of the mammalian RCC1, a guanine nucleotide
      exchange factor for RAN/TC4, and the ubiquitin-activating enzyme E1 involved in
      ubiquitin conjugation, respectively. The ptr3+ gene is essential for cell
      viability, and Ptr3p tagged with green fluorescent protein was localized in both
      the nucleus and the cytoplasm. This is the first report suggesting that the
      ubiquitin system plays a role in mRNA export.

PMID- 9168471
TI  - Identification of detergent-resistant plasma membrane microdomains in
      dictyostelium: enrichment of signal transduction proteins.
AB  - Unlike most other cellular proteins, the chemoattractant receptor, cAR1, of
      Dictyostelium is resistant to extraction by the zwitterionic detergent, CHAPS. We
      exploited this property to isolate a subcellular fraction highly enriched in cAR1
      by flotation of CHAPS lysates of cells in sucrose density gradients. Immunogold
      electron microscopy studies revealed a homogeneous preparation of membrane
      bilayer sheets. This preparation, designated CHAPS-insoluble floating fraction
      (CHIEF), also contained a defined set of 20 other proteins and a single uncharged
      lipid. Cell surface biotinylation and preembedding immunoelectron microscopy both
      confirmed the plasma membrane origin of this preparation. The cell surface
      phosphodiesterase (PDE) and a downstream effector of cAR1, adenylate cyclase
      (ACA), were specifically localized in these structures, whereas the cell adhesion
      molecule gp80, most of the major cell surface membrane proteins, cytoskeletal
      components, the actin-binding integral membrane protein ponticulin, and G-protein
      alpha- and beta-subunits were absent. Overall, CHIFF represents about 3-5% of
      cell externally exposed membrane proteins. All of these results indicate that
      CHIFF is derived from specialized microdomains of the plasma membrane. The method
      of isolation is analogous to that of caveolae. However, we were unable to detect
      distinct caveolae-like structures on the cell surface associated with cAR1, which
      showed a diffuse staining profile. The discovery of CHIFF facilitates the
      purification of cAR1 and related signaling proteins and the biochemical
      characterization of receptor-mediated processes such as G-protein activation and
      desensitization. It also has important implications for the "fluid mosaic" model
      of the plasma membrane structures.

PMID- 9168470
TI  - pp60v-src transformation of rat cells but not chicken cells strongly correlates
      with low-affinity phosphopeptide binding by the SH2 domain.
AB  - Substrates critical for transformation by pp60v-src remain unknown, as does the
      precise role of the src homology 2 (SH2) domain in this process. To continue
      exploring the role of the SH2 domain in pp60v-src-mediated transformation, site
      directed mutagenesis was used to create mutant v-src alleles predicted to encode
      proteins with overall structural integrity intact but with reduced ability to
      bind phosphotyrosine-containing peptides. Arginine-175, which makes critical
      contacts in the phosphotyrosine-binding pocket, was mutated to lysine or alanine.
      Unexpectedly, both mutations created v-src alleles that transform chicken cells
      with wild-type (wt) efficiency and are reduced for transformation of rat cells;
      these alleles are host dependent for transformation. Additionally, these alleles
      resulted in a round morphological transformation of chicken cells, unlike 12 of
      the 13 known host-dependent src SH2 mutations that result in a fusiform
      morphology. Analysis of phosphopeptide binding by the mutant SH2 domains reveal
      that the in vitro ability to bind phosphopeptides known to have a high affinity
      for wt src SH2 correlates with wt (round) morphological transformation in chicken
      cells and in vitro ability to bind phosphopeptides known to have a low affinity
      for wt src SH2 correlates with rat cell transformation. These results suggest
      that the search for critical substrates in rat cells should be among proteins
      that interact with pp60v-src with low affinity.

PMID- 9168472
TI  - Pep7p provides a novel protein that functions in vesicle-mediated transport
      between the yeast Golgi and endosome.
AB  - Saccharomyces cerevisiae pep7 mutants are defective in transport of soluble
      vacuolar hydrolases to the lysosome-like vacuole. PEP7 is a nonessential gene
      that encodes a hydrophilic protein of 515 amino acids. A cysteine-rich tripartite
      motif in the N-terminal half of the polypeptide shows striking similarity to
      sequences found in many other eukaryotic proteins. Several of these proteins are
      thought to function in the vacuolar/lysosomal pathway. Mutations that change
      highly conserved cysteine residues in this motif lead to a loss of Pep7p
      function. Kinetic studies demonstrate that Pep7p function is required for the
      transport of the Golgi-precursors of the soluble hydrolases carboxypeptidase Y,
      proteinase A, and proteinase B to the endosome. Integral membrane hydrolase
      alkaline phosphatase is transported to the vacuole by a parallel intracellular
      pathway that does not require Pep7p function. pep7 mutants accumulate a 40-60-nm
      vesicle population, suggesting that Pep7p functions in a vesicle consumption step
      in vesicle-mediated transport of soluble hydrolases to the endosome. Whereas pep7
      mutants demonstrate no defects in endocytic uptake at the plasma membrane, the
      mutants demonstrate defects in transport of receptor-mediated macromolecules
      through the endocytic pathway. Localization studies indicate that Pep7p is found
      both as a soluble cytoplasmic protein and associated with particulate fractions.
      We conclude that Pep7p functions as a novel regulator of vesicle docking and/or
      fusion at the endosome.

PMID- 9168473
TI  - Tropomyosin-2 cDNA lacking the 3' untranslated region riboregulator induces
      growth inhibition of v-Ki-ras-transformed fibroblasts.
AB  - The levels of high molecular weight isoforms of tropomyosin (TM) are markedly
      reduced in ras-transformed cells. Previous studies have demonstrated that the
      forced expression of tropomyosin-1 (TM-1) induces reversion of the transformed
      phenotype of ras-transformed fibroblasts. The effects of the related isoform TM-2
      on transformation are less clear. To assess the effects of forced expression of
      the TM-2 protein on ras-induced tumorigenicity, we introduced a TM-2 cDNA lacking
      the 3' untranslated region riboregulator into ras-transformed NIH 3T3
      fibroblasts. TM-2 expression resulted in a flatter cell morphology and
      restoration of stress fibers. TM-2 expression also significantly reduced growth
      rates in low serum, soft agar, and nude mice. The reduced growth rates were
      associated with a prolongation of G0-G1. To identify the mechanism of TM-2
      induced growth inhibition, we analyzed the effects of TM-2 reexpression of ERK
      and c-jun N-terminal kinase (JNK) activities. Levels of ERK phosphorylation and
      activity in TM-2-transfected tumor cells were comparable to those in mock
      transfected tumor cells. JNK activity was only modestly increased in ras
      transformed cells relative to untransformed NIH 3T3 cells and only slightly
      reduced as result of forced TM-2 expression. We conclude that the partially
      restored expression of the TM-2 protein induces growth inhibition of ras
      transformed NIH 3T3 cells without influencing ERK or JNK activities. Furthermore,
      the 3' untranslated region riboregulator of the alpha-tropomyosin gene is not
      needed for the inhibition of ras-induced growth.

PMID- 9168476
TI  - Role of Dictyostelium racE in cytokinesis: mutational analysis and localization
      studies by use of green fluorescent protein.
AB  - The small GTPase racE is essential for cytokinesis in Dictyostelium but its
      precise role in cell division is not known. To determine the molecular mechanism
      of racE function, we undertook a mutational analysis of racE. The exogenous
      expression of either wild-type racE or a constitutively active V20racE mutant
      effectively rescues the cytokinesis deficiency of racE null cells. In contrast, a
      constitutively inactive N25racE mutant fails to rescue the cytokinesis
      deficiency. Thus, cytokinesis requires only the activation of racE by GTP and not
      the inactivation of racE by hydrolysis of GTP. To determine the spatial
      distribution of racE, we created a fusion protein with GFP at the amino terminus
      of racE. Remarkably, GFP-racE fusion protein was fully competent to rescue the
      phenotype of racE null cells and, therefore, must reside in the same location as
      native racE. We found that GFP-racE localized to the plasma membrane of the cell
      throughout the entire cell cycle. Furthermore, constitutively active and inactive
      GFP-racE fusion proteins also localized to the plasma membrane. We mapped the
      domain required for plasma membrane localization to the carboxyl-terminal 40
      amino acids of racE. This domain, however, is not sufficient to confer racE
      function onto a closely related GTPase. Taken together, these results suggest
      that racE functions at the cell cortex but it is not involved in determining the
      timing or placement of the contractile ring.

PMID- 9168477
TI  - Appearance of functional connections between neurons resulting from changes in
      the frequency of their spike activity during the performance by animals of
      conditioned-reflex food-procuring responses.
AB  - Cats were conditioned to a food-procuring reflex to time. Correlation analysis
      was applied to multineuron activity in the motor cortex to study the functional
      connections between neurons with changing and constant instantaneous spike
      frequencies on performance by the animals of the passive waiting phase of the
      conditioned reflex, the number of functional connections between "areactive"
      neurons was smaller than that between "reactive" neurons; during the phase of
      active waiting, the numbers of functional connections become similar. The
      increase in the number of functional connections between "areactive" neurons
      during the active waiting phase appears to reflect an intensification of the
      analysis and processing of information, while changes in the functional
      connections between "reactive" neurons was regarded as allowing the possibility
      of correcting functional structures in the case of a rapid change in the
      situation or state of the animal.

PMID- 9168475
TI  - A folded protein can be transported across the chloroplast envelope and thylakoid
      membranes.
AB  - Many thylakoid lumenal proteins are nuclear encoded, cytosolically synthesized,
      and reach their functional location after posttranslational targeting across two
      chloroplast envelope membranes and the thylakoid membrane via proteinaceous
      transport systems. To study whether these transmembrane transport machineries can
      translocate folded structures, we overexpressed the 17-kDa subunit of the oxygen
      evolving complex of photosystem II (prOE17) that had been modified to contain a
      unique C-terminal cysteine. This allowed us to chemically link a terminal 6.5-kDa
      bovine pancreatic trypsin inhibitor (BPTI) moiety to prOE17 to create the
      chimeric protein prOE17-BPTI. Redox reagents and an irreversible sulfhydryl
      specific cross-linker, bis-maleimidohexane, were used to manipulate the structure
      of BPTI. Import of prOE17-BPTI into isolated chloroplasts and thylakoids
      demonstrates that the small tightly folded BPTI domain is carried across both the
      chloroplast envelopes and the delta pH-dependent transmembrane transporter of the
      thylakoid membrane when linked to the correctly targeted OE17 precursor.
      Transport proceeded even when the BPTI moiety was internally cross-linked into a
      protease-resistant form. These data indicate that unfolding is not a ubiquitous
      requirement for protein translocation and that at least some domains of targeted
      proteins can maintain a nonlinear structure during their translocation into and
      within chloroplasts.

PMID- 9168474
TI  - c-kit receptor signaling through its phosphatidylinositide-3'-kinase-binding site
      and protein kinase C: role in mast cell enhancement of degranulation, adhesion,
      and membrane ruffling.
AB  - In bone marrow-derived mast cells (BMMCs), the Kit receptor tyrosine kinase
      mediates diverse responses including proliferation, survival, chemotaxis,
      migration, differentiation, and adhesion to extracellular matrix. In connective
      tissue mast cells, a role for Kit in the secretion of inflammatory mediators has
      been demonstrated as well. We recently demonstrated a role for
      phosphatidylinositide-3' (PI 3)-kinase in Kit-ligand (KL)-induced adhesion of
      BMMCs to fibronectin. Herein, we investigated the mechanism by which Kit mediates
      enhancement of Fc epsilon RI-mediated degranulation, cytoskeletal rearrangements,
      and adhesion in BMMCs. Wsh/Wsh BMMCs lacking endogenous Kit expression, were
      transduced to express normal and mutant Kit receptors containing Tyr-->Phe
      substitution at residues 719 and 821. Although the normal Kit receptor fully
      restored KL-induced responses in Wsh/Wsh BMMCs, Kit gamma 719F, which fails to
      bind and activate PI 3-kinase, failed to potentiate degranulation and is impaired
      in mediating membrane ruffling and actin assembly. Inhibition of PI 3-kinase with
      wortmannin or LY294002 also inhibited secretory enhancement and cytoskeletal
      rearrangements mediated by Kit. In contrast, secretory enhancement and adhesion
      stimulated directly through protein kinase C (PKC) do not require PI 3-kinase.
      Calphostin C, an inhibitor of PKC, blocked Kit-mediated adhesion to fibronectin,
      secretory enhancement, membrane ruffling, and filamentous actin assembly.
      Although cytochalasin D inhibited Kit-mediated filamentous actin assembly and
      membrane ruffling, secretory enhancement and adhesion to fibronectin were not
      affected by this drug. Therefore, Kit-mediated cytoskeletal rearrangements that
      are dependent on actin polymerization can be uncoupled from the Kit-mediated
      secretory and adhesive responses. Our results implicate receptor-proximal PI 3
      kinase activation and activation of a PKC isoform in Kit-mediated secretory
      enhancement, adhesion, and cytoskeletal reorganization.

PMID- 9168478
TI  - Vector coding and neuronal maps.
AB  - A model of vector coding is proposed. An excitation vector is generated in an
      ensemble of neurons, which has simultaneous actions on the map of selective
      detectors (selectors), creating a local excitation maximum which represents the
      input stimulus. Vector coding is also proposed as an explanation for associative
      learning and memory. Responses to the input in this model are determined by the
      excitation vectors triggered by command neurons in ensembles of premotor neurons.

PMID- 9168479
TI  - Similarity of the effects of training and application of serotonin on the
      electrical activity of live hippocampal slices from rats.
AB  - A pronounced sensitization phase was observed on low-frequency stimulation of
      hippocampus slices from rats decapitated immediately after training to a
      conditioned bilateral escape reflex. The same effect was recorded in slices from
      control animals after brief application of serotonin. Serotonin had significantly
      smaller effect on the electrical activity of trained animals. Changes in the
      efficiency of the serotoninergic input to hippocampus neurons are suggested as
      one of the factors eliciting low-frequency facilitation in trained rats.

PMID- 9168480
TI  - Effect of stimulation of the medial geniculate body on the motor polarization
      dominant in rabbits.
AB  - Studies were carried out on the effects of stimulation of the medial geniculate
      body on the course and recovery of a cortical motor polarization dominant created
      in the sensorimotor cortex of the right hemisphere in rabbits. Stimulation of the
      medial geniculate body, on a background of an optimum dominant, elicited a
      movement response of the "dominant" limb. Spectral-coherent analysis of the
      electrical activity of the sensorimotor cortex and medial geniculate body showed
      that stimulation produced changes characteristic of the dominant state in the
      power spectra of the total activity of these structures of the right "dominant"
      half of the brain, as well as in the coherence spectra.

PMID- 9168481
TI  - Interactions of rabbit neocortical neurons during natural food motivation.
AB  - Studies were carried out on the interaction between neurons in the visual and
      sensorimotor, and in the visual and frontal regions of the neocortex of both
      hemispheres in sated and starved rabbits. In starved rabbits, there was an
      increase in number of pairs of neurons with correlated activity, along with an
      increase in the number of pairs of neurons with frequency interactions in the
      theta range and a reduction in the number of pairs with interactions in the alpha
      range; interhemisphere asymmetry occurred in the interaction of neurons in the
      visual and sensorimotor regions. The greatest increase in the number of pairs of
      neurons with correlating activity was seen in the left hemisphere, and a
      preferential sequence of neuron firing appeared.

PMID- 9168482
TI  - Molecular basis of the activity of the dopamine synapse in the mechanisms of
      learning and amnesia.
AB  - The neurochemical correlates of dopamine synapse activity were studied during the
      retrieval of memory traces and in the absence of retrieval ("psychogenic"
      amnesia). The physiochemical parameters of D2 receptor function, the synaptic
      membrane, and the catechol content were assessed in various regions of the brain
      (striatum, neostriatum, hypothalamus, amygdala, frontal cortex, hippocampus,
      nucleus accumbens, and nuclei A9 and A10) in intact, trained, and amnesiac rats.
      It was demonstrated that disturbances in memory trace retrieval were associated
      with decreased activation of synaptic dopamine receptors and alterations in the
      dopamine transformation pathway in the rat brain.

PMID- 9168483
TI  - Features of the coordinated activity functionally identified neurons in the
      hypothalamus in different motivational-emotional states.
AB  - Coordinated activity of hypothalamic neurons associated with motivational and
      reinforcing systems were studied in functional states arising from hunger,
      satiation following food deprivation, "victim" cries, and electrical stimulation
      of the emotionally positive (lateral hypothalamus, lateral preoptic region) and
      negative (dorsomedial tegmentum) reinforcing structures of the hypothalamus.
      Activity characteristics were reflected in the magnitude, sign, and dynamics of
      correlations, and depended on the ratio of motivational and emotional components
      of behavior. The reciprocal nature of the statistical significance of the
      activity of these neurons in conditions in which motivation and emotion dominated
      indicates that the differentiated motivational and emotional hypothalamic
      influences in cortical processes during learning are mediated via the coordinated
      activity of neurons in the motivational and reinforcing systems of the
      hypothalamus.

PMID- 9168484
TI  - Biogenic amine content in the brains of rats with different levels of resistance
      to emotional stress.
AB  - The levels of biogenic amines and of a number of the products of their metabolism
      were studied in the hypothalamic nuclei in Wistar and August rats, which have
      different levels of resistance to emotional stress; levels were also studied in
      structures functionally and anatomically associated with the hypothalamic nuclei,
      i.e., the reticular formation of the midbrain, the amygdaloid body, the septum,
      the locus ceruleus, the dorsal cervical nucleus, and the ventral region of the
      tegmentum. The genotype was found to determine the level of metabolism of
      biogenic amines in structures of the central nervous system in conditions of
      emotional stress. In August rats, the activities of the dopaminergic and
      serotoninergic systems, which are stress-limiting, decreased to a greater extent
      during 24-hour immobilization stress. Adrenaline levels in structures of the
      central nervous system in August rats were higher during stress. Changes in the
      contents of biogenic amines in the paraventricular and ventromedial nuclei of the
      hypothalamus in Wistar and August rats could affect the preganglionic neurons of
      the autonomic nervous system.

PMID- 9168486
TI  - Mechanisms of binocular interaction in the visual cortex of rodents.
AB  - New hypotheses are advanced relating to the functional role and mechanisms of
      interaction of afferentation from the two eyes in the visual cortex of animals
      with poorly developed binocular vision. The proposed approach sheds lights on a
      number of questions, particularly those concerning the relatively large level of
      disparity of the receptor fields in cortical neurons, the role of non-overlapping
      fibers in the visual tract, and others. Hypothesis relating to the evolutionary
      relationships between these mechanisms and the mechanisms of stereopsis are
      discussed.

PMID- 9168485
TI  - Effect of NMDA on the activity of cortical glutaminergic structures in delayed
      visual differentiation in monkeys.
AB  - The effect of intracortical perfusion with the glutamate agonist NMDA on visual
      recognition and short-term memory, as well as an on the responses of visual
      cortex neurons, were studied in rhesus macaques. A microdialysis technique was
      used in combination with multichannel microelectrode recording of single cortical
      cells in the immediate vicinity of the dialysis tube in a behavioral experiment
      in which the monkey had to solve a task involving delayed visual differentiation
      of stimuli of different colors. NMDA altered the characteristics of recognition
      in monkeys. The duration of information storage in short-term memory was
      increased significantly (2-4-fold), and there was a significant reduction in the
      motor response time for all delay periods. These changes were accompanied by a
      significant rearrangement of neuron activity in the visual cortex at all stages
      of the behavioral task. At different stages of the task, 70-85% of the neurons
      showed 2-5-fold increases in activity, while 6-20% showed reductions in activity.
      These results demonstrate an involvement of visual cortex glutaminergic
      structures in the process of visual recognition and short-term memory, as well as
      a nootropic effect obtained by intracortical administration of NMDA.

PMID- 9168487
TI  - Electrophysiological characterization of the functional state of the brain in
      mental disturbances in workers involved in the clean-up following the Chernobyl
      atomic energy station accident.
AB  - Studies were carried out on 150 workers with mental disturbances, who had been
      involved in the clean-up of the Chernobyl atomic energy station accident. Visual
      and computer analyses of EEG traces from 43 workers were compared with traces
      from 17 healthy subjects, and the comparison revealed that the most common
      features in workers were disorganization of the alpha-rhythm and strengthening of
      beta-1-activity in the sensorimotor cortex. In neurosis-like syndromes (13
      patients), there was a significant increase in the power of the alpha-rhythm in
      the anterior parts of the cortex; in psycho-organic states, power as
      significantly reduced (especially in the left hemisphere). Contributing to the
      greater proportion of flat EEG traces in patients with psycho-organic syndromes
      as compared with other groups of patients. Most patients among the clean-up
      workers had increased assimilation of flashing light rhythms and weakening of non
      specific and skin galvanic responses to a light stimulus. It was concluded that
      systemic CNS changes occurred in patients from the clean-up worker groups,
      especially in those with psycho-organic syndrome.

PMID- 9168488
TI  - Changes in the auditory cortex of the brain in situations affecting the
      hypothalamus in clinical states and experimental studies.

PMID- 9168489
TI  - Comparative morphological study of homo- and heterotopic neural transplants.

PMID- 9168490
TI  - State of the cerebral cortex in severe penetrating gunshot injuries to the skull
      and brain (experimental studies).

PMID- 9168491
TI  - Dystrophic and reparative changes in cortical neurons in the offspring of rats
      with moderate prenatal alcoholism.

PMID- 9168492
TI  - Projections of the amygdaloid body and dopaminergic mesencephalic formations in
      the entopeduncular nucleus of the cat brain.

PMID- 9168493
TI  - [Current medical therapies for Crohn's disease in Japan].
AB  - Current available therapies for Crohn's disease in Japan are reviewed in this
      report. Elemental diet is most effective for both inducing and maintaining
      remission in Japan. There appears to be no difference between elemental diet,
      oligopeptide diet and intact nutrients in effectiveness for active Crohn's
      disease. Although corticosteroid is also useful for treating active Crohn's
      disease, low dose of it is not effective for maintaining remission. Steroid has
      important role in combined therapy with elemental diet. New steroid, budesonide
      appears to be fascinate because of less adverse effects. Recently, instead of
      salazosulfapyridine, 5-aminosalicylic acid (5-ASA) proved to be more effective
      not only for active disease but also for maintenance of remission including small
      intestinal type of Crohn's disease with reduced adverse effects. Azathioprine, 6
      mercaptopurine (6-MP), methotrexate and metronidazole are second choice treatment
      in patients whose disease relapse frequently. Although methotrexate appears to be
      effective for active Crohn's disease, the role of it has to be defined. Evidences
      support the use of 5-ASA and methotrexate for prophylaxis after surgery. It is
      important to chose and combine the therapies, thinking of the situation of each
      patient.

PMID- 9168494
TI  - [Team approach of Crohn's disease therapy].
AB  - Under the current conditions that etiologies of Crohn's Disease (CD) are not
      detected and then no radical therapy existed, it is necessary that the CD
      patients can be medically managed by not only medical doctors but also other co
      medical staffs such as nurses, dietitians, social workers and ET (Enterostomal
      Therapist) nurses for their cure & care therapy. There are some different
      therapeutic steps; 1) Nutritional Therapy, 2) Drug Therapy, 3) Surgical Therapy
      and 4) Psychological (Mental) Support. In Japan, Nutritional Therapy headed by
      Elemental Enteral Nutrition is recommended as for 1st choice standard therapy for
      CD patients, who are mainly very young and are required to have themselves
      acceptable for long-term therapeutic controls. Thus, the medical support team
      shall be considerable enough to each patient's life back ground in order to give
      them the whole-mentally therapeutic approach.

PMID- 9168495
TI  - [Laparoscopically assisted surgery for Crohn's disease].
AB  - PURPOSE: Surgical treatment is often required by patients with Crohn's disease
      who have intestinal stricture or fistula. Minimally invasive laparoscopic surgery
      appears to be useful in such patients. Eight cases of intestinal stricture and/or
      fistula treated by laparoscopic surgery are reported. METHODS: In 1997,
      laparoscopic surgery was attempted and successfully completed in 18 patients
      Crohn's disease presenting with intestinal stricture and/or fistula, following
      strict nutritional therapy. Of the 8 patients with a fistula, one had an
      gastrocdic fistula, one had an ileovesical fistula, two had an colic fistula and
      three had ileoileal fistulas. Ileovesical, ileorectal and gastrocolic fistulas
      were divided with an intracorponeal automatic stapling device. Fourteen patients
      underwent ileocecal resection and four underwent ileal resection with
      laparoscopic assistance. RESULTS: Postoperative pain was mild, oral intake was
      started an average of 1.4 days after operation. The patients were discharged an
      average of 8 days after operation. No complication was identified. CONCLUSION: If
      Crohn's disease is treated adequately with conservative therapy, laparoscopic
      surgery is relatively easy, even when there are adhesions and fistulas. Since the
      incision is extremely small with this method, postoperative adhesions are
      minimized. This procedure has the advantage of allowing repeated laparoscopic
      surgery with minimal morbidity. Minimal invasiveness and rapid return to normal
      activity may make laproscopic surgery the treatment of choice for patients with
      Crohn's disease who require surgical treatment.

PMID- 9168496
TI  - [Surgical treatment for Crohn's disease].
AB  - No medical on surgical treatment exists that is ideal for the patient afflicted
      Crohn's disease. During the chronic course of disease various complications or
      significant side effect of medications will develop. At this point, the patient
      is offered an operation. Indication for surgery rarely absolute in Crohn's
      disease with the exception of life threatening emergencies such as free
      perforation or massive hemorrhage. Common indications are bowel obstruction due
      to stenosis, fistula in various sites, abscess and perianal complications. It is
      well known that future likelihood of postoperative "recurrence" of the disease,
      and to learn various operative procedures described in this article. Therefore
      surgeon should be alert to understand the pathophysiology of the disease and to
      learn various operative procedures described in this article. It is important to
      determine proper indication and to choose best timing for operation and select
      the appropriate operative procedures.

PMID- 9168497
TI  - [Non-surgical therapy for ulcerative colitis].
AB  - Ulcerative colitis involving primarily the mucosa of the colon and rectum is a
      diffuse and nonspecific inflammatory disease. Immunocompetent cells infiltrating
      in the inflammed mucosa are mainly lymphocytes, macrophages and neutrophils.
      These activated cells produce proinflammatory cytokines such as IL-1, IL-6, IL-8
      and TNF alpha and inflammatory activators such as PAF, leukotriene,
      prostaglandins, free radicals and proteases, resulting in acute on chronic
      states. Non-surgical therapy for ulcerative colitis includes basic medical
      therapy with sulfasulphapyridine, 5-ASA, corticosteroids and immune suppressive
      drugs as well as new therapies, which are leukocytapheresis, granulocytapheresis,
      anticytokine therapy with antiTNF alpha monoclonal antibody, IL-1ra and IL-10,
      intravenous treatment of massive immunoglobulins and transdermal nicotine
      therapy.

PMID- 9168498
TI  - [Leukocytapheresis for ulcerative colitis].
AB  - Major inclusion criteria for leukocytapheresis (LCAP) therapy were mainly
      insufficient response to conventional drugs therapy. LCAP was administered once a
      week for 5 weeks of intensive therapy and once approximately a month for
      maintenance therapy, for 38 patients with UC. LCAP could remove approximately 1 x
      10(10) white blood cells in each session. In the evaluation, we classified the
      response to the LCAP as: 1) excellent, 2) moderately improved, 3) no change, and
      4) deterioration. Clinical improvement was recognized in 29 of 38 patients (76%)
      including 8 with dramatic response during the intensive therapy, and continued
      throughout the maintenance therapy in 26 patients (68.4%). Even though their
      symptoms were mild, the patients with more than 5 years UC history seemed to be
      not effective. The patients with moderately improvement and with excellent
      response have kept remission for about 20 months and about 2.5 years on an
      average, respectively. Clinical and blood examinations showed no side effects in
      any cases. It suggests that LCAP is able to be a UC treatment between drug
      therapies and an operation.

PMID- 9168499
TI  - [Development of ileal J-pouch anal anastomosis].
AB  - The practical procedures of ileoanal anastomosis (IAA) has developed through the
      two independent lines of thinking. The one idea involved pooling of the
      intestinal content in an ileal reservoir as S-shaped pelvic pouch by Parks. The
      other was the concept of rectal mucosal replacement by Peck who grafted a ileal
      mucosal segment within the totally denuded preserved rectal cuff. The author
      followed on the later concept and constructed an laterally anastomosed
      antiperistaltic looped ileum with which the pouch was able to joint directly to
      the anus in a side to end fashion to form a structure similar to the natural
      rectal ampulla and always spontaneously evacuable. Currently most of the surgeons
      in the world who perform IAA use the technique of the J pouch and in the present
      department, IAA has been performed on 150 patients with UC and 120 with FAP
      during the last 13 years and the number of these patients is ever increasing.
      These evidences suggest the operation that has been established is the superior
      above the other alternative techniques of proctocolectomy.

PMID- 9168501
TI  - [Preservation of anal transitional zone in restorative proctocolectomy].
AB  - Since 1980, restorative proctocolectomy has been established for surgical therapy
      to ulcerative colitis. The crucial points of this procedure are mucosectomy of
      the anorectal mucosa and pouch anal anastomosis. Mucosectomy is often difficult
      due to long standing acute and chronic inflammation and incomplete
      microscopically and leakage of pouch anal anastomosis is relatively high probably
      due to steroid given prior to surgery or direct effect of anorectal mucosal
      inflammation. Regards to postoperative bowel function, nocternal soiling is
      frequently recognized in the patients who received this operation. To overcome
      these technical and functional disadvantages, anal transitional zone preservation
      without mucosectomy and stapled anastomosis between pouch and the upper rim of
      the puborectalis muscle has been performed. Our series of 84 cases with this
      modified method, anastomotic leakage was significantly decreased and nocternal
      soiling was completely disappeared within 7 months postoperatively. And one stage
      procedure became possible unless severe, or high doses of steroid given prior to
      surgery. Only one case of mild dysplasia was experienced in the remaining rectal
      mucosa which was disappeared at the next examination. Medical treatment to the
      remaining lesion was not necessary in the most of cases. Anal canal preservation
      is superior to mucosectomy in the points of bowel function and minimizing
      postoperative complications.

PMID- 9168500
TI  - [Proctocolectomy with ileal W pouch anal anastomosis for ulcerative colitis].
AB  - Restorative proctocolectomy with ileal pouch anal anastomosis, which is a
      relatively new procedure, has become a standard procedure for ulcerative colitis
      (UC) requiring surgical management. The main impact of this procedure is to cure
      patients of disease and to avoid permanent ileostomy, preserving better
      defecatory function and acceptable QOL. Some key aspects of our surgical
      procedure are as follows: 1) two or three separate staged operation, 2) W-shaped
      reservoir, 3) distal rectal mucosectomy and handsewn ileo-anal anastomosis, 4)
      short muscular cuff, and 5) temporary diverting ileostomy. Staged operation and
      diverting ileostomy are helpful to decrease risk of pelvic infection. Total
      removal of the rectal mucosa is necessary to cure the disease, and shorter
      muscular cuff decreases operating time and bleeding and thus the risk of pelvic
      sepsis. The W-shaped reservoir described by Nicholls brings both spontaneous
      defecation and improved function. We have adopted ileal W-pouch among several
      types of reservoir to 58 patients with UC since 1984, and found that a large and
      wide reservoir might allow better defecatory function. There were no cases of
      serious complications and no needs to remove the reservoir. Mean daily stool
      frequency was gradually decreased with time, and 4.9 stools per 24 hours at
      present day, and clinical score of neorectal function also gradually improved
      according to reduction of stool frequency. Seventy three percent of patients felt
      their defecatory function satisfactory and 89% of the patients recovered
      acceptable QOL no less than that obtained during the medically treated period.

PMID- 9168502
TI  - [Useful treatment modality for postoperative duodenal fistula with somatostatin
      analogue].
AB  - A case with leakage of duodenal stump treated by a somatostatin analogue (SMS 201
      995,SMS) effectively was reported. A 39-year-old man had underwent gastric
      resection (Billroth I) and distal pancreaticojejunostomy for transsection of
      duodenal bulbus and pancreatic body. After 14 days later duodenal
      diverticulization was performed due to anastomotic stricture of the gastro
      duodenostomy, which resulted in leakage of duodenal stump and voluminous fluids
      from drains were lasting about 5 weeks. Amylase (AMY) value was shown as high as
      703,812 U/l in the exudate. SMS was injected by 100 micrograms, s, c, by three
      times a day for 24 days. The volume of exudate decreased immediately after the
      administration of SMS and to one-half in volume in 2 weeks. AMY also fell to 42,
      378 U/l. The drain was removed two months after the third surgery. The patient
      was discharged on post operative day 200. SMS was known to inhibit secretion of
      bile and intestinal as well as pancreatic juice and its usefulness for leakage of
      the intestinal tract, especially of the duodenum, is suggested.

PMID- 9168504
TI  - Something is (not) rotten in Denmark [Hamlet (not) W. Shakespeare].

PMID- 9168503
TI  - The preservation of function: treatment of new acquisition of a pathogen.

PMID- 9168505
TI  - Tension-time index of inspiratory muscles in children.

PMID- 9168506
TI  - Antibiotic treatment of initial colonization with Pseudomonas aeruginosa
      postpones chronic infection and prevents deterioration of pulmonary function in
      cystic fibrosis.
AB  - Chronic pulmonary infection with Pseudomonas aeruginosa (PA) develops in most
      patients with cystic fibrosis (CF) and is associated with a poor prognosis. Much
      effort has been directed toward treating the chronic infection, but it is almost
      impossible to eradicate it once established; therefore, prevention is preferable.
      Since 1989 CF patients at the Danish CF Center in Copenhagen have been treated
      with an intensive three-step-protocol consisting of colistin inhalations and oral
      ciprofloxacin at the time of initial PA colonization. This study compares 48
      patients treated according to this intensive protocol with 43 historic controls.
      The study was carried out over 44 months and included 218 patient-years. Only 16%
      of the treated patients developed chronic PA infection after 3 1/2 years compared
      with 72% of the control patients (Kaplan Meier estimate, P < 0.005, log rank
      test). This indicates that aggressive treatment prevented or delayed chronic PA
      infection in 78% of the patients for 3 1/2 years. Furthermore, aggressive
      treatment maintained or increased pulmonary function (forced vital capacity and
      forced expiratory volume in 1 second in percent of predicted values) during the
      year after inclusion compared with the control group, in which pulmonary function
      declined (P < 0.01, Mann-Whitney test). Although some of the treated patients
      eventually developed chronic PA infection, these patients had significantly
      better pulmonary function at the onset of chronic PA infection compared with
      control patients (P < 0.001, Mann-Whitney test). When the different steps in the
      intensive three-step-protocol were analyzed, there was a trend suggesting that 3
      months of high-dose treatment with colistin inhalation and oral ciprofloxacin
      produced the best results in terms of postponement or prevention of chronic PA
      infection (P < 0.05).

PMID- 9168507
TI  - Determinants of the tension-time index of inspiratory muscles in children with
      cystic fibrosis.
AB  - Nutritional status and chronic pulmonary hyperinflation can alter respiratory
      muscle function in cystic fibrosis (CF). This study investigated: 1) whether
      inspiratory muscle function is reduced in children with stable CF in comparison
      with healthy controls; and 2) the mechanisms leading to inspiratory muscle
      weakness, which probably predispose to respiratory muscle fatigue. We determined
      the tension-time index of the inspiratory muscles (TTMUS) noninvasively at rest
      in 16 children with mild to moderate CF (mean age, 11 +/- 2 years) and 10 healthy
      controls (mean age, 11 +/- 2 years). The TTMUS was determined as follows: TTMUS =
      TI/TTOT.PI/PIMAX, where PI is the mean inspiratory pressure estimated from the
      measure of mouth occlusion pressure (P0.1), PIMAX is the maximal inspiratory
      pressure, and TI/TOT is the duty cycle. The results showed similar nutritional
      status in both groups, as well as mild to moderate airway obstruction,
      hyperinflation, and trapped gas in the CF group. In this group only, a
      significant inverse relationship was found between TI/TOT and PI/PIMAX[TITTOT =
      0.482 - (0.388PI/PIMAX), r = -0.53; p < 0.05]. These patients also had greater
      TTMUS (TTMUS = 0.087 +/- 0.030 in CF vs. 0.056 +/- 0.014 in controls, P < 0.01)
      that increased with decreasing lean body mass (r = -0.70, P < 0.005), with
      increasing percent predicted functional residual capacity (r = 0.70, P < 0.05),
      and increasing volumes of trapped gas (r = 0.77, P < 0.01). The multiple linear
      regression analysis for these factors was significant (R2 = 0.84, P < 0.01);
      however, the partial regression coefficient was significant only for lean body
      mass (r2 = 0.60, P < 0.05). Therefore, muscle mass appeared as the strongest
      determinant of TTMUS in CF. This study used a noninvasive method to assess the
      inspiratory muscle performance in children with CF. The results suggest
      impairment in inspiratory muscle function in these children despite good
      nutritional status and only mild to moderate alteration in pulmonary function
      tests. In addition, we were able to investigate some of the determinants of
      inspiratory muscle weakness, namely, muscle mass, hyperinflation, and trapped
      gas, and found that muscle mass played a predominant role.

PMID- 9168508
TI  - Effects of ambient ozone exposures during the spring and summer of 1994 on
      pulmonary function of schoolchildren.
AB  - To investigate the effect of natural exposure to ambient ozone over time, a
      follow-up study of school-aged children was performed in two small towns in
      southwestern Germany (Freudenstadt and Villingen) between March and October of
      1994. Ozone half-hour mean concentrations were measured continuously and
      pulmonary function was tested in each child on four occasions (April, June,
      August, and September). To obtain an average short-term ozone effect, we first
      analyzed the data from the four time points separately and then constructed a
      model that included all information. During the study period the median (5th to
      95th percentile) of all half-hour values of the ozone concentration was 101
      micrograms/m3 or 50.6 ppb (45-179 micrograms/m3 or 22.5-89.8 ppb) in Freudenstadt
      and 64 micrograms/m3 or 32.1 ppb (1 to 140 micrograms/m3 or 0.5-70.1 ppb) in
      Villingen. To assess the effects of an individual ozone exposure we related the
      highest ozone concentration in the respective 24 hours before lung function
      testing to the results of the subconcentration in the respective 24 hours before
      lung function testing to the results of the subsequent pulmonary function tests.
      In the lung function test following the highest ozone exposure, the results of
      our cross-sectional linear regression analysis showed a significant negative
      correlation (P = 0.0181) between ozone exposure and forced vital capacity (FVC).
      In the longitudinal linear regression model we observed a negative statistical
      correlation between ozone exposure and lung function for the subpopulation living
      in the town with the high ozone levels (Freudenstadt). The association was more
      pronounced in boys than girls. For the children in Freudenstadt the decrement of
      FVC was -12.31 ml/10 micrograms/m3 ozone and the decrease in the forced
      expiratory volume in 1 second (FEV1) was -11.29 ml/10 micrograms/m3 ozone.

PMID- 9168509
TI  - Maturation of porcine tracheal cholinergic and inhibitory non-adrenergic, non
      cholinergic innervation.
AB  - It is known that both excitatory cholinergic neural activity and nitric oxide
      (NO) release from inhibitory non-adrenergic, non-cholinergic (iNANC) nerves are
      important determinants of adult human airway smooth muscle tone. However, the
      level of cholinergic and iNANC activity in the newborn is unknown. Therefore,
      isolated trachealis muscle strips were obtained from neonatal, 10-day-old, and
      adult pigs. To quantify cholinergic nerve activity, isometric contractions were
      elicited by stimulating the nicotinic receptors of the cholinergic intramural
      ganglia with dimethyl-phenyl-piperazinium (DMPP). After ganglionic blockade with
      hexamethonium, the post-ganglionic cholinergic nerves were subjected to
      electrical field stimulation (EFS). To assess whether DMPP and EFS were also
      stimulating nitric oxide release from iNANC nerves, the stimulations were
      repeated after NO-synthase inhibition with 3 x 10(-5) M NG-monomethyl-L-arginine
      acetate (LNMMA). All responses were expressed as a percentage of maximal response
      to 10(-4) M acetylcholine. Although no significant age-related differences in the
      contractile responses to DMPP were demonstrated between the three age groups, the
      EFS responses were significantly different. At EFS frequencies of 1 and 2 Hz the
      responses of all three groups were different (P < 0.05, unpaired t-test). At
      frequencies of 0.125 and 0.5 Hz the contractile responses in the neonatal and 10
      day-old groups were less than in the adult animal tissues (P < 0.05, unpaired t
      test). At 4 Hz and above, the responses of the 10-day-old and adult groups became
      greater than the neonatal (P < 0.05, unpaired t-test). LNMMA did not
      significantly increase the contractile responses to DMPP at any age. Only in the
      neonatal rat and 10-day-old groups was a significant increase of the EFS
      frequency responses by LNMMA demonstrated (140.4 +/- 38.2% and 144.2 +/- 41.2%,
      respectively, at 0.5 Hz, ANOVA, P < 0.001). In conclusion, the DMPP responses
      suggest that the neonatal porcine cholinergic innervation is mature at birth.
      This contrasts with a frequency-dependent increase in EFS responses from birth.
      This may be due in part to a relative increase in iNANC modulation of post
      ganglionic cholinergic activity at birth. This mechanism is not responsible for
      the increase in higher EFS frequency responses with post-natal maturation.
      Inhibitory iNANC activity may serve a protective role in the newborn, given the
      reported hyper-responsiveness of airway smooth muscle, small airway caliber, and
      high chest wall compliance at this age.

PMID- 9168510
TI  - Correctly selecting a liquid-filled nasogastric infant feeding catheter to
      measure intraesophageal pressure.
AB  - Polyvinyl chloride (PVC) nasogastric feeding catheters are used clinically to
      measure intraesophageal pressure as an estimate of pleural pressure for
      calculating lung compliance in infants. The accuracy of pressure measurement of 4
      French gauge (FG) catheter sizes and three brands of liquid-filled catheter
      manometer systems (CMS) was evaluated by determining their resonance-frequency
      amplitude and phase properties. All CMS were underdamped and resonated. No CMS
      exhibited a uniform mean frequency response above 11 Hz. The maximum respiratory
      rate (Frr) within which CMS could potentially measure dynamic intraesophageal
      pressure within a 5% error limit was determined (Frr): the highest mean Frr
      recorded reliably in large-diameter catheters was 82 breaths/min. Significant CMS
      differences in accuracy existed between catheter FG sizes and between catheters
      of similar diameters but differing brands. Correlation (r2) between catheter
      inner diameter and CMS Frr was 0.66 across brands. In conclusion, intraesophageal
      PVC liquid-filled feeding catheters are suitable for estimating pleural pressures
      in subjects mechanically ventilated without sharp inspiratory waveforms or high
      respiratory rates. Quantitative frequency response characterization of different
      nasogastric catheter brands and different diameters is mandatory prior to their
      utilization.

PMID- 9168511
TI  - Croup.
AB  - The management of mild to severe croup has undergone dramatic changes in the last
      5 years, primarily due to the increased understanding of the benefits of treating
      it with steroids. Steroids have been used in the treatment of croup for many
      years, but, until recently, their use has remained controversial. Earlier studies
      were often not blinded or used inappropriate outcome measures, such as
      respiratory rate, which have not proven appropriate. Two attempts to review the
      literature in 1980 and 1989 cautiously supported the use of steroids. Despite
      these recommendations many practitioners continued to view croup in most cases as
      a benign self-limited condition, and since steroids have potential side-effects,
      their use was not considered justified. More recently, however, a number of
      developments such as the successful use of the inhaled steroid budesonide and
      oral dexamethasone have reinforced the argument for using steroids. Recent work
      has also shown that both inhaled and systemic steroids work by 1 hour and
      dramatically reduce morbidity and hospitalization time. The demonstration that an
      oral dose of 0.15 mg/kg dexamethasone is as effective as larger doses has made
      the use of systemic steroids more acceptable to many practitioners. All children
      with croup severe enough to be admitted to hospital should receive steroids. Two
      recent studies have shown that steroids also benefitted children who presented to
      emergency departments for treatment, but whose croup was not considered severe
      enough for admission. The type of steroid, the dose, and the mode of
      administration will need to be decided by the attending clinician.

PMID- 9168512
TI  - Bronchitis obliterans due to Mycoplasma pneumonia.

PMID- 9168513
TI  - Non-infectious interstitial alveolitis and foreign body pulmonary vasculitis in a
      child treated for acute lymphoblastic leukemia.
AB  - We report a case of a 14-month-old girl who was treated for acute lymphoblastic
      leukemia but died from interstitial alveolitis associated with foreign body
      vasculitis. This respiratory complication arose 3 months after an allogenic bone
      marrow transplant. No infectious agents (bacteria, virus, or parasite) were
      isolated from bronchial or lung tissue samples. Respiratory complications after
      chemotherapy are reviewed as well as the potential origin of the intravascular
      foreign body.

PMID- 9168514
TI  - Successful combination of amphotericin therapy and surgical resection for fungal
      necrotizing pneumoniae in a child receiving chemotherapy for leukemia.

PMID- 9168515
TI  - Multiple brain abscesses in a 25-year-old patient with cystic fibrosis,
      successfully treated with an anti-Pseudomonas plus anti-mycobacterial antibiotic
      regimen.

PMID- 9168517
TI  - Control of energy balance by a wild ungulate, the kudu (Tragelaphus strepsiceros)
      through adaptive foraging behaviour.

PMID- 9168516
TI  - How can energy balance be achieved by free-living human subjects?

PMID- 9168518
TI  - Human pattern of food intake and fuel-partitioning during weight recovery after
      starvation: a theory of autoregulation of body composition.

PMID- 9168519
TI  - An energy sensor for control of energy intake.
AB  - Control of energy intake, either in response to changes in the energy content of
      food or in energy expenditures and storage, is based on the detection of a
      feedback signal generated in the processing of metabolic fuels for energy.
      Evidence from studies of the fructose analogue, 2,5-AM, indicates a sensor in
      liver responds to changes in intracellular ATP or some closely associated event
      and communicates this information to the brain via vagal afferent neurons. Such a
      mechanism could serve as the energy sensor which controls energy intake.

PMID- 9168520
TI  - Nutrition and poverty in Europe: an overview.

PMID- 9168521
TI  - Hunger, food security and welfare policies: issues and debates in First World
      societies.

PMID- 9168522
TI  - Socio-economic differentials in health: the role of nutrition.

PMID- 9168523
TI  - Developments in the UK: work of the Low Income Project Team.

PMID- 9168524
TI  - Nutrition and poverty in industrialized countries: report of roundtable
      discussion.

PMID- 9168525
TI  - Weaning in Britain: practice, policy and problems.

PMID- 9168526
TI  - Ethnic influences on weaning diet in the UK.

PMID- 9168527
TI  - Weaning and dental health.

PMID- 9168528
TI  - Complementary feeding in developing countries: factors affecting energy intake.

PMID- 9168529
TI  - Adipose tissue metabolism during lactation: where do we go from here?

PMID- 9168530
TI  - Protein metabolism during lactation.

PMID- 9168531
TI  - Mammary-tissue amino acid transport systems.

PMID- 9168532
TI  - Energy expenditure, body composition, and disease risk in children and
      adolescents.
AB  - Recent methodological advances have led to a tremendous improvement in our
      ability to measure energy expenditure, body composition and fat distribution in
      children. The availability of new and improved measurement techniques has greatly
      enhanced the scope of research studies in children. The key findings from the
      present review are as follows: total energy expenditure in young children is
      approximately 25% lower than current recommendations for energy intake and
      revised recommendations are necessary; reduced energy expenditure, however, does
      not necessarily explain the greater prevalence of obesity in the population as a
      whole or in sub-groups at greater risk of obesity; qualitative aspects of
      physical activity (e.g. time, intensity) may be more important than the energy
      expenditure of physical activity in the regulation of body composition; for body
      composition assessment, DXA is emerging as a technique which can substantially
      improve the accuracy and standardization in children; body fat begins to
      accumulate in the obese; waist:hip ratio or waist circumference are inadequate
      markers of intra-abdominal adipose tissue in children and adolescents; finally,
      the early accumulation of fat in the intra-abdominal region is significantly
      related to the development of adverse health effects, including dyslipidaemia and
      glucose intolerance.

PMID- 9168534
TI  - Nutrition and environmental factors in insulin-dependent diabetes mellitus: a
      genetic-epidemiological perspective.

PMID- 9168533
TI  - Diet, politics and disaster: the great Irish famine.

PMID- 9168535
TI  - Early and late nutritional windows for diabetes susceptibility.

PMID- 9168536
TI  - Pancreatic B-cell dysfunction and glucose toxicity in non-insulin-dependent
      diabetes.

PMID- 9168537
TI  - Dietary and lifestyle factors contributing to insulin resistance.

PMID- 9168538
TI  - Lipids, thrombosis and cardiovascular disease in diabetes.

PMID- 9168540
TI  - Folate requirements for health in women.

PMID- 9168539
TI  - Strategies for maintaining good glycaemia control without recurrent
      hypoglycaemia.

PMID- 9168541
TI  - Fear of fatness and adolescent girls: implications for obesity prevention.

PMID- 9168542
TI  - Reproduction: a global nutritional challenge.

PMID- 9168543
TI  - Women and nurture in industrial societies.

PMID- 9168544
TI  - Nutritional issues for women in developing countries.

PMID- 9168545
TI  - Is nutrition important in osteoporosis?

PMID- 9168546
TI  - Controversies surrounding diet and breast cancer.
AB  - What we know about prevention of breast cancer is related to lifetime oestrogen
      exposure and exposures to specific oestrogens at vulnerable periods of life. This
      can be influenced by diet. The strongest indicator of a diet-related effect to
      date is the fairly consistent increase in breast cancer among women who are tall
      or obese (Hunter & Willett, 1993). The other dietary factors summarized in Table
      1 are less strongly associated with breast-cancer risk in epidemiological
      studies. The relationship between fat and breast-cancer risk has been extensively
      studied but remains somewhat uncertain. Fat, as a contributor to energy intakes
      and energy imbalance, is probably a factor in the higher breast-cancer rates in
      Western countries. Beyond its role as an energy source, the evidence for an
      independent effect of dietary fat on breast-cancer risk is weak. More focused
      analyses of the role of individual fatty acids, and on lipid-related pesticide
      exposures, may reveal strong effects which are currently masked by the use of
      inadequate exposure measures, as well as by measurement error. Currently, there
      is substantial evidence of a weak relationship with alcohol consumption, even at
      frequencies of drinking of less than once daily. The evidence of a protective
      role for antioxidants is weaker for breast cancer than for other cancers. This
      might by expected in a cancer which is not strongly associated with cigarette
      smoking. Specific foods are being studied for other potentially-active
      ingredients which may be involved in hormone metabolism, but conclusive results
      for soyabean or cruciferous vegetables are not yet available. Studying these
      relationships will continue to be a challenge for researchers because of the
      difficulties in measuring dietary exposures, which is complicated by the
      uncertainty of the relevant time frame for exposure assessment. While substantial
      attention has been focused on studying diet in relation to incidence, the
      potential for diet to reduce recurrence of breast cancer is thoroughly under
      studied. There is little reason to believe that the factors which influence the
      incidence of breast cancer, perhaps during childhood and puberty, are the same as
      those which affect recurrence in adulthood. In this area, the very limited
      evidence available suggests that study of biologically-active fatty acids is
      promising.

PMID- 9168547
TI  - Cardiovascular risk factors in women.

PMID- 9168548
TI  - Disease and malnutrition in British hospitals.

PMID- 9168549
TI  - Influence of disease on iron status.

PMID- 9168550
TI  - Impact of disease on markers of micronutrient status.

PMID- 9168551
TI  - Impact of disease on markers of macronutrient status.
AB  - It is apparent that illness, particularly acute illness, affects most tests which
      are used to assess macronutrient status. In acutely-ill patients, the best tests
      in terms of specificity for nutritional status are in vivo neutron-activation
      analysis for body composition and N balance as an assessment of recent intake.
      Changes in plasma protein concentration must be interpreted with great care, and
      this is best done in conjunction with changes in the acute-phase-protein
      response. Measurement of plasma IGF-1 may be helpful in the presence of an acute
      phase response, but this requires further validation. In many such patients, the
      most important part of the assessment continues to be the clinical and dietary
      history, together with a careful physical examination. However, the need for
      accurate measurement remains, so that nutritional status and its progress can be
      accurately quantified. This was best expressed many years ago by William
      Thompson, Lord Kelvin, when he stated '... when you can measure what you are
      speaking about and express it in numbers you know something about it... when you
      cannot express it in numbers your knowledge is of a meagre and unsatisfactory
      kind; it may be the beginning of knowledge, but you have scarcely, in your
      thoughts, advanced to the stage of science...'.

PMID- 9168552
TI  - The value of peri-operative nutrition in the sick patient.
AB  - In summary, therefore, the provision of TPN to malnourished patients in the pre
      operative period reduces the incidence of post-operative complications, but does
      not affect post-operative mortality. It is likely that the provision of nutrition
      by the enteral route is as effective as that by the parenteral route, and may
      have the extra benefit of resulting in a reduction in infectious complications
      when compared with patients receiving TPN. Furthermore, the use of enteral
      nutritional support in the post-operative period may also reduce both septic and
      major complications, but does not alter mortality. The use of specific
      combinations of nutrients appears to offer the greatest promise in the use of
      peri-operative nutritional support. The initial studies reported to date
      demonstrate reductions in post-operative morbidity, but again there are no
      benefits on mortality. However, further studies to determine the optimal
      combinations of nutrients for use in patients in the peri-operative period are
      urgently required.

PMID- 9168553
TI  - Vitamin A and human immunodeficiency virus infection.

PMID- 9168554
TI  - Novel lipid sources in parenteral and enteral nutrition.

PMID- 9168555
TI  - The effects of oral vitamin supplementation on cardiovascular risk factors.

PMID- 9168556
TI  - The influence of dietary fat on postprandial lipaemia and factor VII coagulant
      activity in human subjects.

PMID- 9168557
TI  - Apolipoprotein B-48 as a marker for chylomicrons and their remnants: studies in
      the postprandial state.

PMID- 9168558
TI  - Nature's own pharmacy: the diabetes perspective.

PMID- 9168559
TI  - Meat avoidance and body weight concerns: nutritional implications for teenage
      girls.

PMID- 9168560
TI  - Remediation of Wisconsin Card Sorting Test performance in schizophrenia. A
      controlled study.
AB  - Previous studies have shown encouraging plasticity in some schizophrenic
      patients' Wisconsin Card Sorting Test (WCST) performance while receiving detailed
      specific instructions on task and reinforcement. The present study examines the
      efficacy of a modified procedure for WCST administration that bound schizophrenic
      patients to use a conceptually driven cognitive strategy without instruction or
      reinforcement. The schizophrenics' results were also compared to those obtained
      with the same procedure from a matched control sample. By using this procedure,
      63.2% of WCST schizophrenic poor performers dramatically improved their results.
      Schizophrenic poor performers who did not achieve remediation were of a younger
      age at onset and had more negative symptoms. This pattern was strictly associated
      with more perseverative errors on WCST that increased even more when the
      conceptually driven processing was forced. Our findings could have important
      implications for our understanding of the underlying cognitive deficit of the
      poor neuropsychological performance and allow the distinction of schizophrenic
      subtypes who show peculiar features that probably reflect a different
      pathophysiology and would potentially benefit from different modalities of
      treatment and rehabilitation.

PMID- 9168561
TI  - Dissociative symptoms in schizophrenic patients with positive and negative
      symptoms.
AB  - Given the close historical relationship between schizophrenia and dissociative
      disorders, namely multiple personality disorder, we assessed 27 ICD-10 diagnosed
      schizophrenic inpatients for dissociative symptoms using the German version of
      the Dissociative Experience Scale and compared them to a nonclinical control
      group matched for gender and age. Other self-report instruments covering general
      psychopathology, and an expert rating on the predominance of positive or negative
      schizophrenic symptoms, were also administered. Schizophrenic patients have
      significantly more dissociative symptoms than controls. Moreover, patients with a
      plus type of schizophrenia show significantly higher levels of dissociation than
      patients mainly exhibiting less productive symptoms. However, dissociative
      phenomena are only significantly correlated with delusions and hallucinatory
      behavior, and do not show any correlation with other positive symptoms of
      schizophrenia. Severe dissociative psychopathology is also associated with
      impairment in other psychopathological dimensions. The implications of these
      findings are discussed with regard to the theory of dissociation, the
      differential diagnosis between schizophrenia and dissociative disorders and a
      possible contribution of dissociative phenomenology to the clinical heterogeneity
      of schizophrenia.

PMID- 9168562
TI  - Clinical courses of hypochondriac-cenesthopathic symptoms in schizophrenia.
AB  - The systematic detailed clinical studies regarding bodily complaints in
      schizophrenics are relatively few. This paper focuses on the longitudinal courses
      of hypochondriac-cenesthopathic (H-C) symptoms in schizophrenia. From a group of
      183 subjects meeting DSM-III-R criteria for schizophrenia, who were observed for
      at least 5 years, 81 patients with H-C symptoms were selected. The pattern of the
      appearance of their H-C symptoms was investigated. There was a near equality in
      the incidence of acute type and chronic type H-C symptoms. This was also the case
      for the early and tardive types. On the other hand, the complex type was more
      frequent than the simple type. When the H-C symptoms occurred in the acute stage,
      there existed accompanying symptoms as a rule. Among the six clinical courses
      (subtypes) of H-C symptoms, the most frequent was the acute-complex-early type,
      the least frequent was the chronic-simple-early type.

PMID- 9168563
TI  - Three grades of subjective experiences in schizophrenia: their phenomenology and
      implications for initial treatment.
AB  - Subjective experiences (SEs) in schizophrenia are sometimes neglected in
      operationalized diagnostics because schizophrenic patients often distort reality.
      Nevertheless, they sometimes report the peculiar nature of their experiences in a
      form of SEs. Two cases are presented to show the characteristic forms of SEs,
      which represent awareness of disturbed experiences of reality. They correspond to
      SEs in the third grade (SE3s), while SEs in the first grade consist of general
      subjective symptoms regarding mental and nervous conditions and those in the
      second grade indicate awareness of deficits in mental functions. Showing an
      intermediate nature between real and imaginary, SEs as well as first-rank
      symptoms perplex patients in the initial stage of the illness. Labeling SE3s as
      symptoms might successfully reduce the distress and anxiety of patients and be
      helpful in introducing them to long-lasting pharmacotherapy.

PMID- 9168564
TI  - Unilateral hallucinations and other psychotic symptoms due to otosclerosis.
AB  - We report the case of a 35-year-old man suffering from otosclerosis and
      unilateral auditory hallucinations as well as other psychotic symptoms that
      disappeared completely after surgery for otosclerosis. The patient experienced a
      change of his acoustic sensations: the tinnitus was transformed into music, and 4
      months later the music changed into commenting and imperative voices. However, on
      both occasions the transformation from one form to another occurred during an
      alcohol withdrawal syndrome characterized mainly by vivid visual hallucinations.
      Some theoretical considerations on hallucinatory predisposition, development of
      hallucinations, and psychological factors determining psychotic symptoms will be
      discussed.

PMID- 9168565
TI  - Magico-religious beliefs and psychosis.
AB  - In a sample of 80 mothers of psychotic patients from southwestern Greece, 85%
      entertained strong metaphysical beliefs of a magico-religious nature concerning
      the cause of psychotic illness. This finding was more prevalent among the less
      educated. A comparable number of patients with magico-religious delusions had
      mothers who attributed their children's illness to supernatural causes, a finding
      suggesting that family beliefs and attitudes influence the content of the
      patient's delusional thinking. Resorting to exorcism or magic, alone or in
      combination with formal psychiatric help, was very common. Awareness of lay
      beliefs about psychosis and the proper handling of such beliefs by the treating
      psychiatrist may facilitate cooperation with the patient and his family,
      increasing the prospect of a more favorable outcome.

PMID- 9168566
TI  - On interrater reliability for Leonhard's classification of endogenous psychoses.
AB  - Twenty-two patients with a diagnosis of schizophrenia according to DSM-III-R and
      ICD-10 criteria, for whom the long-term courses of illness were all well
      documented, were classified by 4 independent investigators using Leonhard's
      classification of endogenous psychoses. With regard to the large nosological
      groups of cycloid psychoses (including the subtypes of anxiety-happiness
      psychosis, confusional psychosis and motility psychosis), of unsystematic
      schizophrenias (including the subtypes of affect-laden paraphrenia, cataphasia
      and periodic catatonia), and of systematic schizophrenias (divided into
      systematic catatonias, systematic paraphrenias, and hebephrenias), is was
      possible to reach a high level of agreement in the diagnosis, representing a
      Cohen kappa coefficient of 0.82 and 0.89, respectively. In only 2 out of 22
      patients were discrepancies observed in the assignment to the above-mentioned
      groups. This clearly shows the high reliability of Leonhard's classification,
      which allows a differentiated diagnostic and prognostic judgement of
      schizophrenic psychoses according to the DSM-III-R and ICD-10.

PMID- 9168567
TI  - Phenomenology of obsessions in a Turkish series of OCD patients.
AB  - Forty-five outpatients interviewed by using the Structured Clinical Interview for
      DSM-III-R, Outpatient version and diagnosed as obsessive-compulsive disorder were
      evaluated in terms of form and content of obsessions and compulsions. Obsessive
      compulsive phenomena were classified according to a system proposed by Khanna and
      Channabasavanna. Depressive disorder was the most common comorbid diagnosis found
      in 73.2% of patients. The most prevalent obsession themes were daily activities
      and dirt contamination themes (64.4 and 53.3%, respectively). Religious themes
      were infrequent (11.1%) in the sample and Muslim culture seemed not to have a
      prominent impact on phenomenology of the disorder.

PMID- 9168568
TI  - Life events, environmental variables and child depression.
AB  - There is substantial evidence of a significant correlation between life events
      (LE), socio-environmental factors and the occurrence of psychopathological
      disorders. This study investigates the possible influence of these variables on
      depression in children between the ages of 7 and 12 years. We have interviewed
      parents of 15 depressed and 30 control children, and used the Coddington lists of
      LE. From a statistical analysis of the response it emerged that what
      characterises depressed children is a higher number of undesirable and
      uncontrolled events in the recent past and a lower parent educational level. A
      few events in particular appear to be strong risk factors. The event 'outstanding
      personal achievement', much more represented in the control group, seems to be a
      strengthening event and a stress moderator.

PMID- 9168569
TI  - Will ultrasound-screening and ultrasound-guided procedures be replaced by non
      invasive techniques for the diagnosis of fetal chromosome anomalies?

PMID- 9168571
TI  - Development of fetal gyri, sulci and fissures: a transvaginal sonographic study.
AB  - We aimed to determine the feasibility of imaging specific sulci, gyri and
      fissures using transvaginal sonography and to correlate their first sonographic
      recognition with gestational age. Retrospectively, 262 fetal brain scans were
      analyzed from a total of 337 scans. Scans were selected if any of the following
      structures were seen: in the coronal plane the lateral, callosal and cingulate
      sulcus and gyrus; in the median plane the parieto-occipital and calcarine
      fissures, and the cingulate gyrus and sulcus; and, in an oblique section, the
      lateral sulcus. The gestational age at which the fissures, sulci and gyri were
      first imaged was recorded and subsequently compared with similar anatomical
      studies from the literature. It was possible to identify all the targeted
      structures. The gestational ages at which the structures were first imaged were:
      the callosal sulcus, from 14 weeks; the lateral sulcus, from 18 weeks; the
      parieto-occipital sulcus and calcarine fissure, from 18 weeks; and the cingulate
      gyrus, from 26 weeks. We concluded that the developmental maturation of the
      normal fetal brain follows a predictable timetable, and that this maturation can
      be grossly followed with sonography. The sonographic recognition of the fissures,
      gyri and sulci lagged behind the observations by anatomical studies. The greatest
      discrepancy was the first appearance of the cingulate gyrus which, in the
      anatomical studies, could be seen by 18 postmenstrual weeks and, in our study,
      was seen after 26 postmenstrual weeks. The one exception was the callosal sulcus,
      which was first seen at 14 postmenstrual weeks in both the sonographic and
      anatomical studies. In conclusion, the recognition of specific structures of the
      cortical map is possible. Sonography may be used to image the developing cortical
      surface.

PMID- 9168572
TI  - Differential diagnosis and outcome of fetal intracranial hypoechoic lesions:
      report of 21 cases.
AB  - Our objective was to evaluate the diagnostic and prognostic value of sonography
      hypoechoic lesions. A retrospective study revealed revealed a total of 21 cases
      diagnosed over a period of 10 years. Most of the diagnosis were made in the third
      trimester. The presence fluid-filled lesions within the brain matter always
      predicted porencephaly and a poor outcome. In most of these cases (nine out of
      ten), the lesions were seen to communicate with the cavity of the lateral
      ventricles. Among the 11 cases of hypoechoic lesions that were external to the
      brain matter, Doppler ultrasound was always able to distinguish between arachnoid
      cysts (seven cases) and vein of Galen aneurysms (four cases). Arachnoid cysts
      were associated with a good outcome in four out of the five pregnancies that
      delivered at term. Three of the four cases of vein of Galen aneurysm were
      associated with distortion of the cerebral architecture and/or hydrops: one
      pregnancy was terminated and two resulted in early postnatal death. One pregnancy
      with vein of Galen aneurysm and normal cerebral structures, without signs of
      hydrops, had a good outcome. It is concluded that current antenatal ultrasound
      has the capability of accurate differentiation between different clinical
      entities resulting in fetal intracranial hypoechoic lesions, and that the
      sonographic findings have practical clinical implications.

PMID- 9168570
TI  - Seeing harmonics: a new way to view vasculature.

PMID- 9168573
TI  - Comparison between two methods of standardization for gestational age differences
      in fetal nuchal translucency measurement in first-trimester screening for trisomy
      21.
AB  - Our purpose was to compare two different methods of expressing nuchal
      translucency (NT) measurements in first-trimester screening for trisomy 21: the
      difference in millimeters from the median of nuchal translucency (delta value:
      delta NT) and the multiple of the expected median (MoM). Fetal nuchal
      translucency was measured in 32 fetuses with trisomy 21 and in 3180 normal
      fetuses at 9-13 weeks' gestation. For each fetus, the measured nuchal
      translucency was expressed both as a delta value and MoM. The effectiveness of
      the MoM-Gaussian vs. the delta value method in modifying the age-specific risk
      for trisomy 21 was compared by using both the maternal age distribution of our
      study population and the age distribution of a general obstetric population. The
      use of the MoM-Gaussian approach led to a reduction in the false-positive rate at
      a given detection rate, both in the study population (by 1.2-15.2%) and in the
      general population (by 0.4-2.4%). Our results suggest that the use of the MoM
      Gaussian method might confer a potential advantage on the screening performance
      of nuchal translucency in combination with maternal age by decreasing the false
      positive rate. Further studies in larger unselected populations will be needed to
      confirm the effectiveness of this approach.

PMID- 9168574
TI  - The effect of nuchal translucency measurement on second-trimester biochemical
      screening for Down's syndrome.
AB  - In this study we examined the effect of introducing first-trimester nuchal
      translucency measurement on the second-trimester maternal serum screening for
      trisomy 21. The detection rate, false-positive rate, likelihood ratio and
      positive predictive value of the double marker test before and after introduction
      of nuchal translucency measurement were determined. The detection rate of nuchal
      translucency screening for trisomy 21 was 83% (5/6) with a 1.3% false-positive
      rate, a 63.8 likelihood ratio and a positive predictive value of 22.7%. After the
      introduction of nuchal translucency measurement, the likelihood ratio for a
      positive result and positive predictive value of the biochemical screening
      decreased from 9.1 to 5 and 2.7% to 0.45%, respectively. Our results show that
      nuchal translucency measurement is not only an effective method of first
      trimester screening for Down's syndrome but also has implications for the
      likelihood ratio and positive predictive value of second-trimester biochemical
      screening. Since the biochemical test is now applied to a population with a
      decreased risk of trisomy 21, a positive test will be less likely to indicate
      Down's syndrome than when nuchal translucency measurement was not applied.

PMID- 9168575
TI  - Application of transvaginal and abdominal three-dimensional ultrasound for the
      detection or exclusion of malformations of the fetal face.
AB  - In a total of 618 pregnant women between 9 and 37 weeks' gestation, the fetal
      face was evaluated by two-dimensional and three-dimensional ultrasound imaging as
      part of a level III screening evaluation for fetal anomalies. A three-dimensional
      endovaginal probe (5 MHz) was used for examinations at between 9 and 15 weeks,
      and an abdominal three-dimensional probe (3.5 MHz) was used after 15 weeks. Three
      different three-dimensional image display modes were employed: (1) the orthogonal
      display; (2) the surface display; and (3) the transparent display. When we
      studied the three-dimensional orthogonal displays in a 125 cases evaluated by
      abdominal ultrasound, we found that the facial profile shown in the two
      dimensional image represented the true mid-sagittal profile in only 69.6% of the
      cases. In the remaining 30.4%, the profile view deviated from a true mid-sagittal
      section by up to 20 degrees in one or two planes. In a total of 25 facial
      anomalies detected by abdominal ultrasound, 20 were clearly demonstrated by both
      two-dimensional and three-dimensional technology. In the remaining five cases,
      three-dimensional ultrasound revealed or confirmed an additional defect or
      abnormality: a narrow cleft lip in an unfavorable position of the fetal face (n =
      2), a unilateral orbital hypoplasia (n = 1), a cranial ossification defect (n =
      1) and a flat profile in the presence of marked oligohydramnios (n = 1). When
      transvaginal scanning was used, there were cases in which a detailed surface
      image of the fetal face could be obtained as early as 9 weeks' gestation.
      Abdominal scanning routinely yielded high-quality surface images by 20 weeks.
      Three-dimensional ultrasound consistently displayed facial abnormalities with
      greater accuracy and clarity than conventional two-dimensional imaging. This
      particularly applied to chromosomal aberrations and syndromes associated with
      subtle facial abnormalities requiring a detailed evaluation. Not only does three
      dimensional ultrasound help in appreciating the severity of a fetal defect, but
      it can also provide more convincing evidence of a normal fetus than conventional
      two-dimensional sonograms.

PMID- 9168576
TI  - Interfetal heart rate and size variation in first-trimester multifetal
      pregnancies and heart rate of surviving fetuses after fetal reduction.
AB  - The objective of this study was to determine the variation in first-trimester
      fetal size and fetal heart rates in multifetal pregnancies, and to study the
      effect of fetal reduction on the surviving fetal heart rate. Fetal crown-rump
      length and fetal heart rates were measured in 44 patients with multifetal
      pregnancies who underwent fetal reduction. The heart rates of the surviving
      fetuses were also measured immediately after, and 1 h following the procedure. A
      total of 143 fetuses were evaluated prior to reduction and 75 fetuses following
      the procedure. There was no significant difference in crown-rump length between
      fetuses of the same gestation. The interfetal fetal heart rate variation between
      fetuses of the same gestation, expressed as a standard deviation, was 4.78 +/-
      0.51 beats/min (mean standard deviation +/- standard error of the mean) before
      reduction; this was a significantly greater variation than could be attributed to
      error in the measurement of heart rate. In the surviving fetuses, the mean heart
      rate did not change. However, immediately after the reduction, interfetal heart
      rate variation was abolished, but was observed again 1 h after the reduction. We
      conclude that in first-trimester multifetal pregnancies (1) there is no
      significant difference in fetal crown-rump length; (2) there is interfetal
      variation in heart rates; and (3) fetal reduction has only a limited effect on
      the heart rates of surviving fetuses.

PMID- 9168577
TI  - Doppler assessment of tracheal and nasal fluid flow during fetal breathing
      movements: preliminary observations.
AB  - Our aim was to determine if it was technically possible to assess fetal tracheal
      fluid flow during fetal breathing movements, and to compare the data obtained
      with those recorded in the fetal nasopharynx. Tracheal and nasal fluid flow was
      analyzed in ten uncomplicated pregnancies, the gestational age ranging between 28
      and 38 weeks. Color Doppler was used to detect the fluid displacement in the
      trachea generated by fetal breathing movements. Spectral Doppler was then used to
      analyze the fluid flow velocity waveforms. During the same breathing episode,
      nasal fluid flow was assessed by the same technique. The inspiration and
      expiration times were variable and not statistically comparable for both nasal
      and tracheal flow. Peak velocities of inspired and expired fluid were higher in
      the trachea than in the nose (p < 0.05). We found that the peak velocity of
      tracheal flow waveforms was significantly higher for inspiration than expiration
      (p < 0.05). No significant differences were found in the time velocity integral
      between inspiration and expiration (p = 0.79). The calculated intratracheal flow
      volume displaced during one breathing cycle increased from 1.3 to 5.0 ml with
      advancing gestation. Assessment of nasal and tracheal flow, using color and
      spectral Doppler, is feasible in the human fetus. Intratracheal flow measurements
      may provide an insight into the effect of fetal breathing movements on lung fluid
      in the human fetus.

PMID- 9168578
TI  - Effect on fetal circulation of low-dose aspirin for prevention and treatment of
      pre-eclampsia and intrauterine growth restriction: Doppler flow study.
AB  - The use of low-dose aspirin for the prevention and treatment of pre-eclampsia and
      intrauterine growth restriction has been studied extensively during the last 10
      years. The large clinical trials do not support routine prophylaxis or
      therapeutic administration of low-dose aspirin in high-risk pregnant patients. We
      report on 87 Israeli women who were recruited for the CLASP study (a
      collaborative trial for the prevention and treatment of pre-eclampsia and
      intrauterine growth restriction). Of these women, 41 were treated with 60 mg
      aspirin daily, and 46 with placebo. The fetal circulation was evaluated by
      repeated Doppler flow waveform measurements of the umbilical artery and
      descending aorta from 20 to 34 weeks of gestation. The peak-systolic/ lowest
      diastolic velocity ratio, pulsatility index and resistance index were calculated.
      No significant differences in Doppler measurements were observed for any of the
      indices between the aspirin and placebo groups. There were no statistically
      significant changes in the flow parameters during the course of pregnancy in any
      of the women studied, nor was there a correlation between waveform analysis and
      pregnancy outcome. Thus, based on the present results, it appears that low-dose
      aspirin does not improve fetal circulation parameters.

PMID- 9168579
TI  - Harmonic imaging of porcine intraovarian arteries using sonographic contrast
      medium: initial findings.
AB  - The purpose of this study was to visualize, using harmonic gray-scale imaging,
      blood flow in porcine intraovarian arteries after intravenous injections of a
      bubble-based sonographic contrast medium. Five female pigs underwent laparotomy.
      Surgically isolated ovaries were scanned intraperitoneally by an ultrasound
      system reconfigured with software changes to accomplish harmonic imaging. The
      transmission and receiving frequencies were set at 3.75 and 7.5 MHz,
      respectively. After injection of the sonographic contrast medium (Aerosomes) into
      a peripheral vein, the ovaries were imaged in the harmonic mode. Ten minutes
      later, another contrast injection was administered and conventional gray-scale
      imaging of the ovary performed. In all five pigs, intraovarian arteries were
      clearly identified upon harmonic imaging as brightly echogenic moving columns.
      The arterial blood pool appeared brighter during systole than diastole. Upon
      ultrasound contrast-assisted conventional gray-scale imaging, intraovarian
      arteries were not visualized in four pigs and poorly visualized in one. We
      conclude that contrast-assisted harmonic imaging can adequately visualize blood
      flow in intraovarian arteries of surgically exposed porcine ovaries. Clinically,
      harmonic imaging may facilitate early detection of tumor-induced angiogenesis in
      the human ovary.

PMID- 9168580
TI  - Pathology and clinical implications of abnormal umbilical artery Doppler
      waveforms.

PMID- 9168581
TI  - Early growth retardation.

PMID- 9168582
TI  - Solid-appearing pelvic hydatic cyst: transabdominal and transvaginal sonographic
      diagnosis.

PMID- 9168583
TI  - Risk of wrist injury from repetitive use of ultrasound transducers.

PMID- 9168584
TI  - Exploring the roles of peer and adult video models for infant imitation.
AB  - Research seeking to determine whether imitation of gestures is within the
      neonate's and young infant's competence has yielded discrepant findings. Some
      studies report imitation of at least one gesture, tongue protrusion, whereas
      others fail to find significant matching of even this action for infants aged 1
      to 4 months. Videotaped presentations of a peer and an adult modeling tongue
      protrusions and mouth opening/closing were shown to infants with mean ages of 13
      and 23 weeks in an attempt to test the efficacy of peer models and to free
      modeling from any potential bias. With both baseline and arousal controls to
      assess the significance of tongue protrusions and mouth openings to their
      respective models, no significant effects of modeling were discernible at either
      age in Study 1, Study 2 was conducted to address possible design limitations of
      the first investigation. Only one significant effect favoring an interpretation
      of imitative matching was obtained; it occurred at 12 weeks, following video
      presentations of tongue protrusions by an adult. This single effect may have been
      a chance result. Granting the two-dimensionality of the video image, imitative
      like matching appears not to be engendered with great efficacy by a dynamic
      pattern that preserves characteristics of facial gestures, whether the gestures
      are modeled by an infant peer or by an adult.

PMID- 9168585
TI  - An additional facet of the incest taboo: a protection of the mating-strategy
      template.
AB  - It is suggested that sexual intercourse between adult males and girls tends to
      distort an inherent mating-strategy template: female choice of mating partner.
      The distortion seems to have long-range consequences in the form of myriad
      psychopathologies, which, in turn, reduce the afflicted individuals' chances for
      normative marriage and parenting profiles. In addition, a similar dynamic would
      hypothetically result from adult-male to boy incest. It is suggested that to
      minimize the chances of adult-child sexual intercourse, incest taboos have
      historically been reinforced and extended to nonparental adults, especially men,
      beyond the immediate nuclear family.

PMID- 9168586
TI  - Category superiority effects in young and elderly adults.
AB  - Recent research indicates that some elderly persons experience an age-related
      visual processing deficit, for which they may attempt to compensate through the
      use of relational information. This hypothesis was tested, using the category
      superiority effect as a model system. In studies of young adults, the category
      superiority effect has been shown to be confined to relatively abstract stimulus
      materials such as verbal items, and to be absent for more concrete
      representations such as photographs of actual objects. However, it was predicted
      that, contrary to the data from young adults, a category superiority effect would
      be present in elderly adults for both verbal and pictorial stimuli, because
      elderly people would be expected to use category information to compensate for
      imageric deficits. This prediction was confirmed, consistent with the hypothesis.

PMID- 9168587
TI  - Cigarette smoking in young adults: childhood and adolescent personality,
      familial, and peer antecedents.
AB  - Three models (independent, interdependent, and mediational) were hypothesized in
      this study, to examine the interrelation of personality, family, and peer
      determinants and their effects on tobacco use by young adults. Mothers were first
      interviewed about their children when they were between the ages of 1 and 10
      years old. Three subsequent interviews were conducted with the children when they
      reached adolescence and young adulthood. Results show support for the mediational
      model. In accordance with family interactional framework conceptions, there was a
      sequence in patterning: from parenting during early adolescence; to personality
      and peer factors, extending to smoking in late adolescence; and culminating in
      smoking in adulthood. With a developmental approach, a number of psychosocial
      measures were related in both younger and older children. Nevertheless, some
      interesting developmental differences emerged. The findings suggest at least four
      possible targets for therapeutic or preventive intervention: the parent, the
      child, the adolescent, and the peer group.

PMID- 9168588
TI  - Motor control differentiates children's from adults' drawings for child and adult
      judges.
AB  - In two exploratory studies, motor skill as a possible distinctive feature for
      differentiating drawings made by second-grade children and by college students
      was tested by having child and adult judges sort drawings made by children and by
      adults. Adults drew with their preferred (motorically skilled) or nonpreferred
      (nonmotorically skilled) hand. Children and adults were equally accurate in
      discriminating children's from adults' preferred-hand drawings, but child judges
      confused children's and adults' non-preferred-hand drawings. Child, but not
      adult, judges confused adults' preferred-hand and adults' non-preferred-hand
      drawings. Thus, children were sensitive to characteristics of drawings that
      depended on motor skill when it was an additional feature of difference but not
      when it was the only distinctive feature. Motor control effects in constructing
      drawings and evidence of motor control in responding to drawings warrant further
      study and perhaps greater emphasis in theories of drawing development.

PMID- 9168589
TI  - Toward a theoretically based measurement model of the good life.
AB  - A theoretically based conceptualization of the good life should differentiate 4
      dimensions-the hedonist good life, the dialectical good life, the humanist good
      life, and the formalist good life. These 4 dimensions incorporate previous
      fragmentary measures, such as life satisfaction, depression, work alienation, and
      marital satisfaction, to produce an integrative view. In the present study, 276
      Hong Kong Chinese husbands and wives responded to a survey of 13 indicators for
      these 4 good life dimensions. Confirmatory hierarchical factor analysis showed
      that these indicators identified the 4 dimensions of the good life, which in turn
      converged to identify a second-order factor of the overall good life. The model
      demonstrates discriminant validity in that the first-order factors had high
      loadings on the overall good life factor despite being linked by a social
      desirability factor. Analysis further showed that the second-order factor model
      applied equally well to husbands and wives. Thus, the conceptualization appears
      to be theoretically and empirically adequate in incorporating previous
      conceptualizations of the good life.

PMID- 9168590
TI  - The relationship between parental locus of control and children's perceptions of
      control.
AB  - Parents' beliefs about locus of control in relation to their children were
      measured. Previous studies have failed to find a relationship between parental
      locus of control and children's locus of control. The results of this study
      indicate that an external parental locus of control was related to children's
      attributing their successes and failures to unknown causes. There was also a
      strong correlation between parental locus of control and children's behavior
      toward the parent.

PMID- 9168591
TI  - Middle- and working-class black and white children's speech during a picture
      labeling task.
AB  - The speech of 9 middle-class Black, 9 middle-class White, 9 working-class Black,
      and 9 working-class White preschool children was examined during a picture
      labeling task. The groups were found to be similar in levels and forms of
      labeling. There were class differences and race differences among the children:
      Middle-class and White children labeled more and provided more information about
      objects. Existing data from the children's parents indicate that there are many
      ways in which the groups of children resemble and differ from their parents in
      their labeling. The present findings demonstrate the influence of social context
      in shaping children's labeling and the simultaneous influence of the children's
      independent structuring of their labeling.

PMID- 9168592
TI  - Individual variations in the spatial profile of human macular pigment.
AB  - Individual variations in the spatial profile of macular pigment (MP) density were
      measured for 32 subjects. Peak density of MP measured with a 460-nm, 12-arcmin
      stimulus averaged 0.58, standard deviation (SD) = 0.26, with a range of 0.175 to
      1.39. To assess the symmetry of the MP distribution, MP density was measured on
      the horizontal and vertical meridians at +/-1 deg eccentricity. The density
      varied by no more than 16% at these four locations, indicating a basically
      symmetric distribution. Based on a linear interpolation between measured
      locations, the width of the spatial distribution of MP at half the maximal
      density averaged 1.03 deg, SD = 0.38, with a range of 0.25 to 1.9 deg. The
      average spatial profile of MP density across subjects was fitted with both an
      exponential and a Gaussian function. An exponential decay with eccentricity
      explained more variance in the data than did a Gaussian function. Assuming an
      exponential decay with eccentricity, once MP density has been measured in the
      center of the retina (denoted A), MP density at more eccentric locations (X, deg)
      can be predicted with a standardized equation (MP = A x 10(-0.42x)). For
      individual cases, small deviations from an exponential function suggest the
      existence of minor flanking peaks or shoulders for 40% of the subjects. We also
      examined the temporal stability of the MP profile of four subjects over a time
      span of 4-14 months and for a single spatial location for ten subjects over a
      time span of 1-16 years. These longitudinal data show that differences in MP
      density among subjects are maintained over time, if dietary patterns are stable.

PMID- 9168593
TI  - New objective classification system for nuclear opacification.
AB  - We have developed an autonomous objective classification scheme for degree of
      nuclear opacification. The algorithm was developed by using a series of color 35
      mm slides acquired with a Topcon photo slit-lamp microscope and use of standard
      camera settings. The photographs were digitized, and first, and second-order gray
      level statistics were extracted from within circular regions of the nucleus.
      Classifications of severity were performed by using these features as input to a
      neural network. Training versus classification performance was tested by using
      photographs of different eyes, and test/retest classification reproducibility was
      evaluated by using paired photographs of the same eyes. We demonstrate good
      performance of the classifier against subjective assessments rendered by the
      Wilmer grading system [Invest. Ophthalmol. Visual Sci. 29, 73 (1988)] and
      markedly better test/retest reproducibility.

PMID- 9168594
TI  - Decreases in the critical disparity gradient with eccentricity may reflect the
      size-disparity correlation.
AB  - The interaction between dot separation and fusible disparity limits (critical
      disparity gradient) was assessed at 0, 2, 4, and 8 deg eccentricity by 19
      subjects. The critical disparity gradient showed a significant decrease with
      eccentricity such that larger separations were required for fusion of a given
      disparity as eccentricity increased. An argument is put forth that this
      relationship supports a size-disparity correlation. The significant disparity
      eccentricity interaction may be explained by both the progressive loss of higher
      spatial-frequency channels with eccentricity and a reduction in the range of
      disparities processed by a channel as eccentricity is increased. Individual
      differences in the trend across eccentricity are noted and discussed.

PMID- 9168595
TI  - Brightness fading during Ganzfeld adaptation.
AB  - The time course and extent of brightness fading in a Ganzfeld were determined for
      adapting luminances ranging from 0.01 to 100 cd/m2. Magnitude estimation and
      interocular brightness matching were used. During Ganzfeld adaptation, perceived
      brightness decreased slowly and leveled off, on average, after 5-7 min (adapting
      time increasing with luminance). On average, the total brightness loss was
      equivalent to a 1.2 log unit reduction in luminance, independent of adapting
      luminance. The residual brightness perceived at the final plateau was generally
      higher than the brightness of the Eigengrau, suggesting a partially sustained
      luminance channel.

PMID- 9168596
TI  - Role of remote adaptation in perceived subjective color.
AB  - Light adaptation to illumination that is presented peripherally changes the
      subjective color of a central Benham disk stimulus. In our experiments we kept
      the peripheral illumination achromatic and remote (not even adjacent to the test
      stimulus). Using a high-frame-rate monitor, we produced the subjective color
      stimulus, to our knowledge for the first time, on a computer screen in emulation
      of the Benham disk programs. The resulting changes in the perceived subjective
      color were as follows: (1) Remote adapting illumination caused a dramatic shift
      in the perceived subjective color with a span from red to green; (2) there was a
      trade-off dependence between the area and the intensity of the remote adapting
      illumination with respect to the perceived color of the test stimulus; (3) the
      effect of the remote adaptation showed no interocular interaction. This finding
      suggests that the effect is elicited from a low-level stage in the visual
      pathway. In addition, we were able to approximate experimentally the spatial
      profile of the contribution of the remote illumination through the shift in the
      perceived color. We also found an opposite general trend of color shifts that
      occurred when either the central stimulus luminance or the remote illumination
      was increased. A suggested model for the reversed color shifts trend is
      discussed.

PMID- 9168597
TI  - Yeast as a navigational aid in genome analysis. 1996 Kathleen Barton-Wright
      Memorial Lecture.

PMID- 9168598
TI  - A 12 kb nucleotide sequence containing the alanine dehydrogenase gene at 279
      degrees on the Bacillus subtilis chromosome.
AB  - In the framework of the European project aimed at the sequencing of the Bacillus
      subtilis genome, a DNA fragment of 12315 bp was cloned and sequenced. The DNA
      fragment is located between rrnB (275 degrees) and pai (284 degrees). Twelve ORFs
      were predicted to encode putative proteins. Two of these (ald and yukl) coincided
      with known B. subtilis genes. The products of two other genes (yukK and yukL)
      showed significant similarity to known proteins present in databases, e.g.
      pyoverdin synthase of Pseudomonas aeruginosa and pristinamycin synthase D of
      Streptomyces pristinaespiralis.

PMID- 9168599
TI  - Physical mapping shows that the unstable oxytetracycline gene cluster of
      Streptomyces rimosus lies close to one end of the linear chromosome.
AB  - A restriction map of the 8 Mb linear chromosome of Streptomyces rimosus R6-501
      was constructed for the enzymes Asel (13 fragments) and Dral (7 fragments).
      Linking clones for all 12 Asel sites and 5 of the 6 Dral sites were isolated. The
      chromosome has terminal inverted repeats of 550 kb, which are the longest yet
      reported for a Streptomyces species. The oxytetracycline gene cluster lies about
      600 kb from one end, which might account for its frequent spontaneous
      amplification and deletion. Several other markers were localized on the
      chromosome (dnaA and recA, the rrn operons, the attachment site for pSAM2 and
      prophages RP2 and RP3). Comparison of the conserved markers with the map of
      Streptomyces coelicolor A3(2) suggested there are differences in genome
      organization between the two species.

PMID- 9168600
TI  - Isolation and characterization of a strong promoter element from the Streptomyces
      ghanaensis phage I19 using the gentamicin resistance gene (aacC1) of Tn 1696 as
      reporter.
AB  - A promoter-probe shuttle plasmid (pGL7011) containing the promoterless
      aminoglycoside-O-acetyltransferase I gene (aacC1) of Tn1696 was used to isolate
      DNA fragments from Streptomyces ghanaensis phage I19 that possessed promoter
      activity in Streptomyces lividans TK23. Analysis of gentamicin (Gm) resistance
      levels in Escherichia coli and in S. lividans TK23, and of aacC1 mRNA levels in
      S. lividans, identified a fragment (F14) that exhibited a high level of promoter
      activity in both species. Subsequent analysis revealed that the promoter activity
      of SF14 (a subcloned fragment of F14) was about twice that of ermEp*, one of the
      strongest characterized actinomycete promoters. SF14 contained two tandemly
      arranged promoters, 14-Ip and p14-IIp, with overlapping and adjacent -10 and -35
      regions, respectively. Both promoters appear to be recognized with different
      efficiencies by the major RNA polymerase holoenzyme (E sigma hrdB) of
      Streptomyces coelicolor A3(2).

PMID- 9168601
TI  - Identification by PCR of genes encoding multiple response regulators.
AB  - Environmental sensing in bacteria often involves the concerted action of sensor
      kinases and response regulators. Degenerate oligonucleotide primers were designed
      on the basis of amino acid similarity in the response regulators of these two
      component systems. The primers were used in PCR to specifically amplify an
      internal DNA segment corresponding to the receiver module domain from genes
      encoding response regulators. Amplification products of the expected size were
      obtained from 12 different Gram-positive and Gram-negative bacteria. Sequence
      analysis revealed that 22 DNA fragments, which clearly originated from response
      regulator genes, were amplified from Escherichia coli, Agrobacterium tumefaciens,
      Bacillus subtilis and Lactobacillus bulgaricus. In each of these four species the
      receiver module of putative response regulator genes, which do not seem to be
      related to any of the already characterized genes, was identified. This simple
      and powerful method is therefore particularly useful for discovering new signal
      transduction systems which cannot be revealed by usual genetic studies.

PMID- 9168602
TI  - FNR-dependent repression of ndh gene expression requires two upstream FNR-binding
      sites.
AB  - The ndh gene of Escherichia coli encodes a non-proton-translocating NADH
      dehydrogenase (NdhII) that is anaerobically repressed by the global transcription
      regulator, FNR. FNR binds at two sites (centred at -50.5 and -94.5) in the ndh
      promoter but the mechanism of FNR-mediated repression appears not to be due to
      promoter occlusion. This mechanism has been investigated using an aerobically
      active derivative of FNR, FNR* (FNR-D154A), with ndh promoters containing altered
      FNR-binding sites. FNR* repressed ndh gene expression both aerobically and
      anaerobically in vivo. Gel retardation analysis and DNase I footprinting with
      purified FNR* protein confirmed that FNR interacts at two sites in the ndh
      promoter, and that FNR and RNA polymerase (RNAP) can bind simultaneously. Studies
      with three altered ndh promoters, each containing an impaired or improved FNR
      site, indicated that both FNR-sites are needed for efficient repression in vivo.
      The alpha-subunit of RNAP interacted with two regions (centred at -105 and -46),
      each overlapping one of the FNR-sites in the ndh promoter. Footprints of the FNR*
      RNAP-ndh ternary complex indicated that FNR*-binding at -50.5 prevents the alpha
      subunit of RNAP from docking with the DNA just upstream of the -35 element.
      Binding of a second FNR* molecule at the -105 site likewise prevents binding of
      the alpha-subunit at its alternative site, thus providing a plausible mechanism
      for FNR-mediated repression based on displacement of the alpha-subunit of RNAP.

PMID- 9168603
TI  - The outer membrane of lipid A-deficient Escherichia coli mutant LH530 has reduced
      levels of OmpF and leaks periplasmic enzymes.
AB  - We have previously described a new Escherichia coli K-12 mutant, LH530, which has
      a defective outer membrane. LH530 is very sensitive to hydrophobic antibiotics,
      does not grow at 42 degrees C and synthesizes reduced amounts of lipid A.
      Phenotypically LH530 is very similar to the known lipid A biosynthesis mutants of
      E. coli and Salmonella typhimurium. Its genetic defect is not known, but the
      defect is suppressed by multiple copies of ORF195. Here we show that at 37
      degrees C LH530 contains a reduced amount of the OmpF porin and that it leaks
      periplasmic beta-lactamase at 37 degrees C and 42 degrees C. We further show that
      ORF195, when present at low copy number, restores the antibiotic resistance and
      lipid A biosynthesis of LH530 at 28 degrees C, but not at higher temperatures. In
      contrast, OmpF expression is restored at 37 degrees C.

PMID- 9168604
TI  - The flagellin N-methylase gene fliB and an adjacent serovar-specific IS200
      element in Salmonella typhimurium.
AB  - The cloning and molecular genetic analysis of a locus mapping within the
      flagellar gene (fli) complex of Salmonella typhimurium is reported. A copy of the
      insertion element IS200 was located in a noncoding stretch of DNA upstream of the
      fliA gene. Comparative nucleotide sequence analysis showed that this copy of
      IS200 was 711 bp long and that its flanking regions contained no features common
      to other characterized insertion sites of this element. The element was located
      37 bp downstream of an ORF whose product was shown by interspecific transfer and
      amino acid analysis to carry out N-methylation of selected lysine residues in
      Salmonella flagellin. The sequence and phenotype of this ORF identified it as
      fliB, encoding the only prokaryotic N-methylase acting on amino groups to have
      been characterized to date. It was found to be conserved among all clinically
      significant serovars of Salmonella. The IS200 insertion site is of particular
      interest since it was conserved in all but two rare evolutionary lines of S.
      typhimurium, and was absent from 85 Salmonella strains belonging to 37 other
      serovars. It is thus a phylogenetically significant marker at the serovar level.

PMID- 9168605
TI  - Brucella abortus strain 2308 putative glucose and galactose transporter gene:
      cloning and characterization.
AB  - The gene for the putative transporter for glucose and galactose from Brucella
      abortus strain 2308 was isolated by functional complementation of Escherichia
      coli strains lacking either glucose or galactose transport systems. The same two
      plasmid clones were isolated from each screen. These clones restored glucose and
      galactose transport to the respective E. coli strains. The sequence of the 1806
      bp overlap between these two plasmids was determined. A 1242 bp ORF whose
      disruption eliminated complementation of both E. coli strains showed 36% identity
      with the E. coli fucP gene encoding a fucose transporter. These two transporters
      are members of the major facilitator superfamily, in which they represent a
      previously undescribed family. In addition, an incomplete gene similar to E. coli
      hisG was found. One of the plasmids complemented E. coli hisG mutants.

PMID- 9168606
TI  - Escherichia coli flavohaemoglobin (Hmp) reduces cytochrome c and Fe(III)
      hydroxamate K by electron transfer from NADH via FAD: sensitivity of
      oxidoreductase activity to haem-bound dioxygen.
AB  - Escherichia coli flavohaemoglobin (Hmp) reduced purified mitochondrial cytochrome
      c aerobically in a reaction that was not substantially inhibited by superoxide
      dismutase, demonstrating that superoxide anion, the product of O2 reduction by
      Hmp, did not contribute markedly to cytochrome c reduction. Cytochrome c was
      reduced by Hmp even in the presence of 0.5 mM CO, when the haem B was locked in
      the ferrous, low-spin state, demonstrating that electron transfer to cytochrome c
      from NADH was via FAD, not haem. Hmp also reduced the ferrisiderophore complex
      Fe(III)-hydroxamate K from Rhizobium leguminosarum bv. viciae anaerobically in a
      CO-insensitive manner, but at low rates and with low affinity for this substrate.
      The NADH-cytochrome c oxidoreductase activity of Hmp was slightly sensitive to
      the binding and reduction of O2 at the haem. The Vmax of cytochrome c reduction
      fell from 7.1 s-1 in the presence of 0.5 mM CO to 5.0 s-1 in the presence of 100
      microM O2, with no significant change in K(m) for cytochrome c (6.8 to 7.3
      microM, respectively). O2 at near-micromolar concentrations diminished cytochrome
      c reduction to a similar extent as did 100 microM O2. Thus, Hmp acts as a
      reductase of broad specificity, apparently without involvement of electron
      transfer via the globin-like haem. These data are consistent with the hypothesis
      that Hmp could act as an intracellular sensor of O2 since, in the absence of O2,
      electron flux from FAD to other electron acceptors increases. However, the nature
      of such acceptors in vivo is not known and alternative models for O2 sensing are
      also considered.

PMID- 9168607
TI  - Use of a glycerol-limited, long-term chemostat for isolation of Escherichia coli
      mutants with improved physiological properties.
AB  - The evolution of Escherichia coli MG1655 mutants was followed over 126 d in a
      glycerol-limited chemostat at a dilution rate of 0.05 h-1. This corresponds to a
      total of 217 generations at a doubling time of 13.9 h. After this time, nearly
      90% of the chemostat population consisted of evolved mutant strains as determined
      by their altered colony morphologies on plates. Two mutants were isolated that
      exhibited generally improved growth phenotypes in batch cultivations on glycerol,
      glucose or the gluconeogenic substrate acetate. Higher specific growth rates and
      increased biomass yields were found for both mutants. For one mutant, this
      behaviour was combined with significantly reduced secretion of overflow
      metabolites when either glycerol or glucose was the carbon source. Additionally,
      during all growth phases of a batch cultivation, this mutant exhibited increased
      resistance to a variety of adverse conditions including heat shock, osmotic
      stress and nutrient deprivation. It also displayed significantly shorter lag
      phases.